Three controlled trials of interventions to increase recruitment to a randomized controlled trial of mobile phone based smoking cessation support.

PubMed

Free, Caroline; Hoile, Elizabeth; Robertson, Steven; Knight, Rosemary

2010-06-01

Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment. We report three controlled trials of interventions to increase recruitment to the Txt2stop trial. To evaluate: Trial 1. The impact on registrations of a text message regarding an online registration facility; Trial 2. The impact on randomizations of sending pound5 with a covering letter to those eligible to join the trial; Trial 3. The impact on randomizations of text messages containing quotes from existing participants. Single blind controlled trials with allocation concealment. Trial 1: A text message regarding our new online registration facility; Trial 2: A letter with pound5 enclosed; Trial 3: A series of four text messages containing quotes from participants. The control group in each trial received standard Txt2stop procedures. Trial 1: 3.6% (17/470) of the intervention group and 1.1% (5/467) of the control group registered for the trial, risk difference 2.5% (95% CI 0.6-4.5). 0% (0/ 470) of the intervention group and 0.2% (1/467) of the control group registered successfully online, risk difference -0.2 (95% CI -0.6-0.2); Trial 2: 4.5% (11/246) of the intervention group and 0.4% (1/245) of the control group were randomized into the Txt2stop trial, risk difference 4.0% (95% CI 1.4-6.7); Trial 3: 3.5% (14/405) of the intervention group and 0% (0/406) of the control group were randomized into the Txt2stop trial, risk difference 3.5 (95% CI 1.7-5.2). There were no baseline data available for trial 1. Allocation of participant IDs in trials 2 and 3 were systematic. Sending a text message about an online registration facility increased registrations to Txt2stop, but did not increase online registrations. Sending a pound5 reimbursement for participants' time and sending text messages containing quotes from existing participants increased randomizations into the Txt2stop trial. Clinical Trials 2010; 7: 265-273. http://ctj.sagepub.com.

Registration status and methodological reporting of randomized controlled trials in obesity research: A review.

PubMed

Byrne, Jillian L S; Yee, Tamara; O'Connor, Kathleen; Dyson, Michele P; Ball, Geoff D C

2017-04-01

To assess registration and reporting details of randomized controlled trials (RCTs) published from 2011 to 2016 across four obesity journals. All issues from four leading obesity journals were searched systematically for RCTs from January 2011 to June 2016. Data on registration status were extracted from manuscripts, online trial registries, and a trial database; corresponding authors were contacted for registration details, when necessary. The methodological reporting of RCTs was assessed on specific criteria from the Consolidated Standards of Reporting Trials. A total of 223 RCTs were reviewed. Three-quarters (n = 170) were registered publicly; 94 (55.3%) reported registration details in the manuscript, and 82 (48.2%) were registered prospectively. Newer RCTs were more likely to be registered prospectively than older RCTs (2014-2016: 57.3% vs. 2011-2013: 39.2%; c 2  = 5.5, P = 0.02). Assessment on the Consolidated Standards of Reporting Trials demonstrated that less than half of all studies reported data collection dates (n = 108; 48.4%) or included "randomized trial" in the title (n = 89; 39.9%). The methodological reporting of RCTs published in obesity journals is suboptimal, despite current guidelines and policies. To complement existing standards, editorial boards should incorporate mandatory fields within the online manuscript submission process to enhance the quality, transparency, and comprehensiveness of reporting RCTs in obesity journals. © 2017 The Obesity Society.

Statistical analysis plan for the Pneumatic CompREssion for PreVENting Venous Thromboembolism (PREVENT) trial: a study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen; Al-Hameed, Fahad; Burns, Karen E A; Mehta, Sangeeta; Alsolamy, Sami; Almaani, Mohammed; Mandourah, Yasser; Almekhlafi, Ghaleb A; Al Bshabshe, Ali; Finfer, Simon; Alshahrani, Mohammed; Khalid, Imran; Mehta, Yatin; Gaur, Atul; Hawa, Hassan; Buscher, Hergen; Arshad, Zia; Lababidi, Hani; Al Aithan, Abdulsalam; Jose, Jesna; Abdukahil, Sheryl Ann I; Afesh, Lara Y; Dbsawy, Maamoun; Al-Dawood, Abdulaziz

2018-03-15

The Pneumatic CompREssion for Preventing VENous Thromboembolism (PREVENT) trial evaluates the effect of adjunctive intermittent pneumatic compression (IPC) with pharmacologic thromboprophylaxis compared to pharmacologic thromboprophylaxis alone on venous thromboembolism (VTE) in critically ill adults. In this multicenter randomized trial, critically ill patients receiving pharmacologic thromboprophylaxis will be randomized to an IPC or a no IPC (control) group. The primary outcome is "incident" proximal lower-extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation, whereas the patients and treating team will be unblinded. The trial has 80% power to detect a 3% absolute risk reduction in the rate of proximal DVT from 7% to 4%. Consistent with international guidelines, we have developed a detailed plan to guide the analysis of the PREVENT trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes, and defines covariates for adjusted analyses a priori. Application of this statistical analysis plan to the PREVENT trial will facilitate unbiased analyses of clinical data. ClinicalTrials.gov , ID: NCT02040103 . Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506 . Registered on 30 October 2013.

Parenting Programmes for Preventing Tobacco, Alcohol or Drugs Misuse in Children Less than 18: A Systematic Review

ERIC Educational Resources Information Center

Petrie, Jane; Bunn, Frances; Byrne, Geraldine

2007-01-01

We conducted a systematic review of controlled studies of parenting programmes to prevent tobacco, alcohol or drug abuse in children less than 18. We searched Cochrane Central Register of Controlled Trials, specialized Register of Cochrane Drugs and Alcohol Group, Pub Med, psych INFO, CINALH and SIGLE. Two reviewers independently screened studies,…

Relaxation techniques for pain management in labour.

PubMed

Smith, Caroline A; Levett, Kate M; Collins, Carmel T; Crowther, Caroline A

2011-12-07

Many women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute towards the popularity of complementary methods of pain management. This review examined currently available evidence supporting the use of relaxation therapies for pain management in labour. To examine the effects of relaxation methods for pain management in labour on maternal and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2010), The Cochrane Complementary Medicine Field's Trials Register (November 2011), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 4), MEDLINE (1966 to 30 November 2010), CINAHL (1980 to 30 November 2010), the Australian and New Zealand Clinical Trial Registry (30 November 2010), Chinese Clinical Trial Register (30 November 2010), Current Controlled Trials (30 November 2010), ClinicalTrials.gov, (30 November 2010) ISRCTN Register (30 November 2010), National Centre for Complementary and Alternative Medicine (NCCAM) (30 November 2010) and the WHO International Clinical Trials Registry Platform (30 November 2010). Randomised controlled trials comparing relaxation methods with standard care, no treatment, other non-pharmacological forms of pain management in labour or placebo. Three review authors independently assessed trials for inclusion and extracted data. Data were checked for accuracy. Two review authors independently assessed trial quality. We attempted to contact study authors for additional information. We included 11 studies (1374 women) in the review. Relaxation was associated with a reduction in pain intensity during the latent phase (mean difference (MD) -1.25, 95% confidence interval (CI) -1.97 to -0.53, one trial, 40 women) and active phase of labour (MD -2.48, 95% CI -3.13 to 0.83, two trials, 74 women). There was evidence of improved outcomes from relaxation instruction with increased satisfaction with pain relief (risk ratio (RR) 8.00, 95% CI 1.10 to 58.19, one trial, 40 women) and lower assisted vaginal delivery (RR 0.07, 95% CI 0.01 to 0.50, two trials, 86 women). Yoga was associated with reduced pain (mean difference (MD) -6.12, 95% CI -11.77 to -0.47), one trial, 66 women), increased satisfaction with pain relief (MD 7.88, 95% CI 1.51 to 14.25, one trial, 66 women), satisfaction with the childbirth experience (MD) 6.34, 95% CI 0.26 to 12.42, one trial, 66 women), and reduced length of labour when compared to usual care (MD -139.91, 95% CI -252.50 to -27.32, one trial, 66 women) and when compared with supine position (MD -191.34, 95% CI -243.72 to -138.96, one trial, 83 women). Trials evaluating music and audio analgesia found no difference between groups in the primary outcomes pain intensity, satisfaction with pain relief, and caesarean delivery. The risk of bias was unclear for the majority of trials. Relaxation and yoga may have a role with reducing pain, increasing satisfaction with pain relief and reducing the rate of assisted vaginal delivery. There was insufficient evidence for the role of music and audio-analgesia. However, there is a need for further research.

Vitamin K for upper gastrointestinal bleeding in people with acute or chronic liver diseases.

PubMed

Martí-Carvajal, Arturo J; Solà, Ivan

2015-06-09

Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. Several treatments are used for upper gastrointestinal bleeding in people with liver diseases. One of them is vitamin K administration, but it is not known whether it benefits or harms people with acute or chronic liver disease and upper gastrointestinal bleeding. This is an update of this Cochrane review. To assess the beneficial and harmful effects of vitamin K for people with acute or chronic liver disease and upper gastrointestinal bleeding. We searched The Cochrane Hepato-Biliary Controlled Trials Register (February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2 of 12, 2015), MEDLINE (Ovid SP) (1946 to February 2015), EMBASE (Ovid SP) (1974 to February 2015), Science Citation Index EXPANDED (1900 to February 2015), and LILACS (1982 to 25 February 2015). We sought additional randomised trials from two registries of clinical trials: the World Health Organization Clinical Trials Search Portal and the metaRegister of Controlled Trials. We looked through the reference lists of the retrieved publications and review articles. Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. We considered observational studies for assessment of harms only. \\We aimed to summarise data from randomised clinical trials using Standard Cochrane methodology and assess them according to the GRADE approach. We found no randomised trials on vitamin K for upper gastrointestinal bleeding in people with liver diseases assessing benefits and harms of the intervention. We identified no quasi-randomised studies, historically controlled studies, or observational studies assessing harms. This updated review found no randomised clinical trials of vitamin K for upper gastrointestinal bleeding in people with liver diseases. The benefits and harms of vitamin K need to be tested in randomised clinical trials. Until randomised clinical trials are conducted to assess the trade-off between benefits and harms, we cannot recommend or refute the use of vitamin K for upper gastrointestinal bleeding in people with liver diseases.

The effect of berberine on insulin resistance in women with polycystic ovary syndrome: detailed statistical analysis plan (SAP) for a multicenter randomized controlled trial.

PubMed

Zhang, Ying; Sun, Jin; Zhang, Yun-Jiao; Chai, Qian-Yun; Zhang, Kang; Ma, Hong-Li; Wu, Xiao-Ke; Liu, Jian-Ping

2016-10-21

Although Traditional Chinese Medicine (TCM) has been widely used in clinical settings, a major challenge that remains in TCM is to evaluate its efficacy scientifically. This randomized controlled trial aims to evaluate the efficacy and safety of berberine in the treatment of patients with polycystic ovary syndrome. In order to improve the transparency and research quality of this clinical trial, we prepared this statistical analysis plan (SAP). The trial design, primary and secondary outcomes, and safety outcomes were declared to reduce selection biases in data analysis and result reporting. We specified detailed methods for data management and statistical analyses. Statistics in corresponding tables, listings, and graphs were outlined. The SAP provided more detailed information than trial protocol on data management and statistical analysis methods. Any post hoc analyses could be identified via referring to this SAP, and the possible selection bias and performance bias will be reduced in the trial. This study is registered at ClinicalTrials.gov, NCT01138930 , registered on 7 June 2010.

Prevalence of clinical trial status discrepancies: A cross-sectional study of 10,492 trials registered on both ClinicalTrials.gov and the European Union Clinical Trials Register.

PubMed

Fleminger, Jessica; Goldacre, Ben

2018-01-01

Trial registries are a key source of information for clinicians and researchers. While building OpenTrials, an open database of public trial information, we identified errors and omissions in registries, including discrepancies between descriptions of the same trial in different registries. We set out to ascertain the prevalence of discrepancies in trial completion status using a cohort of trials registered on both the European Union Clinical Trials Register (EUCTR) and ClinicalTrials.gov. We used matching titles and registry IDs provided by both registries to build a cohort of dual-registered trials. Completion statuses were compared; we calculated descriptive statistics on the prevalence of discrepancies. 11,988 dual-registered trials were identified. 1,496 did not provide a comparable completion status, leaving 10,492 trials. 16.2% were discrepant on completion status. The majority of discrepancies (90.5%) were a 'completed' trial on ClinicalTrials.gov inaccurately marked as 'ongoing' on EUCTR. Overall, 33.9% of dual-registered trials described as 'ongoing' on EUCTR were listed as 'completed' on ClinicalTrials.gov. Completion status on registries is commonly inaccurate. Previous work on publication bias may underestimate non-reporting. We describe simple steps registry owners and trialists could take to improve accuracy.

Are two penicillins better than one? A systematic review of oral flucloxacillin and penicillin V versus oral flucloxacillin alone for the emergency department treatment of cellulitis.

PubMed

Quirke, Michael; O'Sullivan, Ronan; McCabe, Aileen; Ahmed, Jameel; Wakai, Abel

2014-06-01

Flucloxacillin either alone or combined with penicillin V is still the first-line antibiotic drug of choice for the treatment of cellulitis in emergency departments (EDs) in Ireland. The rationale for this antibiotic regimen is their anti-staphylococcal and anti-streptococcal activity. To determine the clinical efficacy, tolerability and safety of oral flucloxacillin alone (monotherapy) compared with a combination of flucloxacillin with penicillin V (dual therapy) in the ED-directed outpatient treatment of cellulitis. We searched the following electronic databases: MEDLINE (1950 to August 2011), EMBASE (1980 to August 2011), Cochrane Central Register of Controlled Clinical Trials (CENTRAL) (The Cochrane Library 2011, Issue), OpenGrey, Current Controlled Trials metaRegister of Clinical Trials (August 2011) and reference lists and websites of potential trials. We performed cross-referencing from the reference lists of major articles on the subject. We imposed no language restriction. Despite a comprehensive literature search to identify relevant studies, no randomized-controlled trials that fulfilled the inclusion criteria were found. Despite its common use, there are no published randomized-controlled trials comparing flucloxacillin monotherapy with a combination of flucloxacillin and penicillin V in the ED management of cellulitis. We discuss existing European and North American prescribing rationale and current guidelines.

Promoting deceased organ and tissue donation registration in family physician waiting rooms (RegisterNow-1 trial): study protocol for a pragmatic, stepped-wedge, cluster randomized controlled registry.

PubMed

Li, Alvin H; Garg, Amit X; Prakash, Versha; Grimshaw, Jeremy M; Taljaard, Monica; Mitchell, Joanna; Matti, Danny; Linklater, Stefanie; Naylor, Kyla L; Dixon, Stephanie; Faulds, Cathy; Bevan, Rachel; Getchell, Leah; Knoll, Greg; Kim, S Joseph; Sontrop, Jessica; Bjerre, Lise M; Tong, Allison; Presseau, Justin

2017-12-21

There is a worldwide shortage of organs available for transplant, leading to preventable mortality associated with end-stage organ disease. While most citizens in many countries with an intent-to-donate "opt-in" system support organ donation, registration rates remain low. In Canada, most Canadians support organ donation but less than 25% in most provinces have registered their desire to donate their organs when they die. The family physician office is a promising yet underused setting in which to promote organ donor registration and address known barriers and enablers to registering for deceased organ and tissue donation. We developed a protocol to evaluate an intervention to promote registration for organ and tissue donation in family physician waiting rooms. This protocol describes a planned, stepped-wedge, cluster randomized registry trial in six family physician offices in Ontario, Canada to evaluate the effectiveness of reception staff providing patients with a pamphlet that addresses barriers and enablers to registration including a description of how to register for organ donation. An Internet-enabled tablet will also be provided in waiting rooms so that interested patients can register while waiting for their appointments. Family physicians and reception staff will be provided with training and/or materials to support any conversations about organ donation with their patients. Following a 2-week control period, the six offices will cross sequentially into the intervention arm in randomized sequence at 2-week intervals until all offices deliver the intervention. The primary outcome will be the proportion of patients visiting the office who are registered organ donors 7 days following their office visit. We will evaluate this outcome using routinely collected registry data from provincial administrative databases. A post-trial qualitative evaluation process will assess the experiences of reception staff and family physicians with the intervention and the stepped-wedge trial design. Promoting registration for organ donation in family physician offices is a potentially useful strategy for increasing registration for organ donation. Increased registration may ultimately help to increase the number of organs available for transplant. The results of this trial will provide important preliminary data on the effectiveness of using family physician offices to promote registration for organ donation. ClinicalTrials.gov, ID: NCT03213171 . Registered on 11 July 2017.

Intrauterine resuscitation during the second stage of term labour by maternal hyperoxygenation versus conventional care: study protocol for a randomised controlled trial (INTEREST O2).

PubMed

Bullens, Lauren M; Hulsenboom, Alexandra D J; Moors, Suzanne; Joshi, Rohan; van Runnard Heimel, Pieter J; van der Hout-van der Jagt, M Beatrijs; van den Heuvel, Edwin R; Guid Oei, S

2018-03-23

Perinatal asphyxia is, even in developed countries, one the major causes of neonatal morbidity and mortality. Therefore, if foetal distress during labour is suspected, one should try to restore foetal oxygen levels or aim for immediate delivery. However, studies on the effect of intrauterine resuscitation during labour are scarce. We designed a randomised controlled trial to investigate the effect of maternal hyperoxygenation on the foetal condition. In this study, maternal hyperoxygenation is induced for the treatment of foetal distress during the second stage of term labour. This study is a single-centre randomised controlled trial being performed in a tertiary hospital in The Netherlands. From among cases of a suboptimal or abnormal foetal heart rate pattern during the second stage of term labour, a total of 116 patients will be randomised to the control group, where normal care is provided, or to the intervention group, where before normal care 100% oxygen is supplied to the mother by a non-rebreathing mask until delivery. The primary outcome is change in foetal heart rate pattern. Secondary outcomes are Apgar score, mode of delivery, admission to the neonatal intensive care unit and maternal side effects. In addition, blood gas values and malondialdehyde are determined in umbilical cord blood. This study will be the first randomised controlled trial to investigate the effect of maternal hyperoxygenation for foetal distress during labour. This intervention should be recommended only as a treatment for intrapartum foetal distress, when improvement of the foetal condition is likely and outweighs maternal and neonatal side effects. EudraCT, 2015-001654-15; registered on 3 April 2015. Dutch Trial Register, NTR5461; registered on 20 October 2015.

Non-commercial vs. commercial clinical trials: a retrospective study of the applications submitted to a research ethics committee.

PubMed

Fuentes Camps, Inmaculada; Rodríguez, Alexis; Agustí, Antonia

2018-06-01

There are many difficulties in undertaking independent clinical research without support from the pharmaceutical industry. In this retrospective observational study, some design characteristics, the clinical trial public register and the publication rate of noncommercial clinical trials were compared to those of commercial clinical trials. A total of 809 applications of drug-evaluation clinical trials were submitted from May 2004 to May 2009 to the research ethics committee of a tertiary hospital, and 16.3% of trials were noncommercial. They were mainly phase IV, multicentre national, and unmasked controlled trials, compared to the commercial trials that were mainly phase II or III, multicentre international, and double-blind masked trials. The commercial trials were registered and published more often than noncommercial trials. More funding for noncommercial research is still needed. The results of the research, commercial or noncommercial, should be disseminated in order not to compromise either its scientific or its social value. © 2018 The British Pharmacological Society.

Using ClinicalTrials.gov to supplement information in ophthalmology conference abstracts about trial outcomes: a comparison study.

PubMed

Scherer, Roberta W; Huynh, Lynn; Ervin, Ann-Margret; Dickersin, Kay

2015-01-01

Including results from unpublished randomized controlled trials (RCTs) in a systematic review may ameliorate the effect of publication bias in systematic review results. Unpublished RCTs are sometimes described in abstracts presented at conferences, included in trials registers, or both. Trial results may not be available in a trials register and abstracts describing RCT results often lack study design information. Complementary information from a trials register record may be sufficient to allow reliable inclusion of an unpublished RCT only available as an abstract in a systematic review. We identified 496 abstracts describing RCTs presented at the 2007 to 2009 Association for Research in Vision and Ophthalmology (ARVO) meetings; 154 RCTs were registered in ClinicalTrials.gov. Two persons extracted verbatim primary and non-primary outcomes reported in the abstract and ClinicalTrials.gov record. We compared each abstract outcome with all ClinicalTrials.gov outcomes and coded matches as complete, partial, or no match. We identified 800 outcomes in 152 abstracts (95 primary [51 abstracts] and 705 [141 abstracts] non-primary outcomes). No outcomes were reported in 2 abstracts. Of 95 primary outcomes, 17 (18%) agreed completely, 53 (56%) partially, and 25 (26%) had no match with a ClinicalTrials.gov primary or non-primary outcome. Among 705 non-primary outcomes, 56 (8%) agreed completely, 205 (29%) agreed partially, and 444 (63%) had no match with a ClinicalTrials.gov primary or non-primary outcome. Among the 258 outcomes partially agreeing, we found additional information on the time when the outcome was measured more often in ClinicalTrials.gov than in the abstract (141/258 (55%) versus 55/258 (21%)). We found no association between the presence of non-matching "new" outcomes and year of registration, time to registry update, industry sponsorship, or multi-center status. Conference abstracts may be a valuable source of information about results for outcomes of unpublished RCTs that have been registered in ClinicalTrials.gov. Complementary additional descriptive information may be present for outcomes reported in both sources. However, ARVO abstract authors also present outcomes not reported in ClinicalTrials.gov and these may represent analyses not originally planned.

Searching ClinicalTrials.gov and the International Clinical Trials Registry Platform to inform systematic reviews: what are the optimal search approaches?

PubMed

Glanville, Julie M; Duffy, Steven; McCool, Rachael; Varley, Danielle

2014-07-01

Since 2005, International Committee of Medical Journal Editors (ICMJE) member journals have required that clinical trials be registered in publicly available trials registers before they are considered for publication. The research explores whether it is adequate, when searching to inform systematic reviews, to search for relevant clinical trials using only public trials registers and to identify the optimal search approaches in trials registers. A search was conducted in ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP) for research studies that had been included in eight systematic reviews. Four search approaches (highly sensitive, sensitive, precise, and highly precise) were performed using the basic and advanced interfaces in both resources. On average, 84% of studies were not listed in either resource. The largest number of included studies was retrieved in ClinicalTrials.gov and ICTRP when a sensitive search approach was used in the basic interface. The use of the advanced interface maintained or improved sensitivity in 16 of 19 strategies for Clinicaltrials.gov and 8 of 18 for ICTRP. No single search approach was sensitive enough to identify all studies included in the 6 reviews. Trials registers cannot yet be relied upon as the sole means to locate trials for systematic reviews. Trials registers lag behind the major bibliographic databases in terms of their search interfaces. For systematic reviews, trials registers and major bibliographic databases should be searched. Trials registers should be searched using sensitive approaches, and both the registers consulted in this study should be searched.

Efficacy of botulinum toxins on bruxism: an evidence-based review.

PubMed

Long, Hu; Liao, Zhengyu; Wang, Yan; Liao, Lina; Lai, Wenli

2012-02-01

The objective of this study was to assess the efficacy of botulinum toxins on bruxism. Electronic databases (PubMed, Embase and Science Citation Index), websites (Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) and the literature database of SIGLE (System for Information on Grey Literature in Europe) were searched from January 1990 to April 2011 for randomised controlled trials or nonrandomised studies assessing the efficacy of botulinum toxins on bruxism. There was no language restriction. Through a predefined search strategy, we retrieved 28 studies from PubMed, 94 from Embase, 60 from the Science Citation Index, two ongoing clinical trials and two from the Cochrane Central Register of Controlled Trials. Of these, only four studies met our inclusion criteria and were finally included. Of the four included studies, two were randomised controlled trials and two were controlled before-and-after studies. These studies showed that botulinum toxin injections can reduce the frequency of bruxism events, decrease bruxism-induced pain levels and satisfy patients' self-assessment with regard to the effectiveness of botulinum toxins on bruxism. In comparison with oral splint, botulinum toxins are equally effective on bruxism. Furthermore, botulinum toxin injections at a dosage of <100 U are safe for otherwise healthy patients. Botulinum toxin injections are effective on bruxism and are safe to use. Therefore, they can be used clinically for otherwise healthy patients with bruxism. © 2012 FDI World Dental Federation.

Thromboprophylaxis using combined intermittent pneumatic compression and pharmacologic prophylaxis versus pharmacologic prophylaxis alone in critically ill patients: study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen M; Alsolamy, Sami; Al-Dawood, Abdulaziz; Al-Omari, Awad; Al-Hameed, Fahad; Burns, Karen E A; Almaani, Mohammed; Lababidi, Hani; Al Bshabshe, Ali; Mehta, Sangeeta; Al-Aithan, Abdulsalam M; Mandourah, Yasser; Almekhlafi, Ghaleb; Finfer, Simon; Abdukahil, Sheryl Ann I; Afesh, Lara Y; Dbsawy, Maamoun; Sadat, Musharaf

2016-08-03

Venous thromboembolism (VTE) remains a common problem in critically ill patients. Pharmacologic prophylaxis is currently the standard of care based on high-level evidence from randomized controlled trials. However, limited evidence exists regarding the effectiveness of intermittent pneumatic compression (IPC) devices. The Pneumatic compREssion for preventing VENous Thromboembolism (PREVENT trial) aims to determine whether the adjunct use of IPC with pharmacologic prophylaxis compared to pharmacologic prophylaxis alone in critically ill patients reduces the risk of VTE. The PREVENT trial is a multicenter randomized controlled trial, which will recruit 2000 critically ill patients from over 20 hospitals in three countries. The primary outcome is the incidence of proximal lower extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the scans are blinded to intervention allocation, whereas the patients and caregivers are unblinded. The trial has 80 % power to detect a 3 % absolute risk reduction in proximal DVT from 7 to 4 %. The first patient was enrolled in July 2014. As of May 2015, a total of 650 patients have been enrolled from 13 centers in Saudi Arabia, Canada and Australia. The first interim analysis is anticipated in July 2016. We expect to complete recruitment by 2018. Clinicaltrials.gov: NCT02040103 (registered on 3 November 2013). Current controlled trials: ISRCTN44653506 (registered on 30 October 2013).

A systematic review of the evidence on home care reablement services.

PubMed

Legg, Lynn; Gladman, John; Drummond, Avril; Davidson, Alex

2016-08-01

To determine whether publically funded 'reablement services' have any effect on patient health or use of services. Systematic review of randomized controlled trials and non-randomized studies in which reablement interventions were compared with no care or usual care in people referred to public-funded personal care services. Data sources included: Cochrane Central Register of Controlled Trials, EPOC register of studies, trials registers, Medline, EMBASE, and CINHAL. Searches were from 2000 up to end February 2015. Not applicable. Investigators' definition of the target population for reablement interventions. Use of publically funded personal care services and dependence in personal activities of daily living. We found no studies fulfilling our inclusion criteria that assessed the effectiveness of reablement interventions. We did note the lack of an agreed understanding of the nature of reablement. Reablement is an ill-defined intervention targeted towards an ill-defined and potentially highly heterogeneous population/patient group. There is no evidence to suggest it is effective at either of its goals; increasing personal independence or reducing use of personal care services. © The Author(s) 2015.

Single dental implant retained mandibular complete dentures – influence of the loading protocol: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Over the years, there has been a strong consensus in dentistry that at least two implants are required to retain a complete mandibular denture. It has been shown in several clinical trials that one single median implant can retain a mandibular overdenture sufficiently well for up to 5 years without implant failures, when delayed loading was used. However, other trials have reported conflicting results with in part considerable failure rates when immediate loading was applied. Therefore it is the purpose of the current randomized clinical trial to test the hypothesis that immediate loading of a single mandibular midline implant with an overdenture will result in a comparable clinical outcome as using the standard protocol of delayed loading. Methods/design This prospective nine-center randomized controlled clinical trial is still ongoing. The final patient will complete the trial in 2016. In total, 180 edentulous patients between 60 and 89 years with sufficient complete dentures will receive one median implant in the edentulous mandible, which will retain the existing complete denture using a ball attachment. Loading of the median implant is either immediately after implant placement (experimental group) or delayed by 3 months of submerged healing at second-stage surgery (control group). Follow-up of patients will be performed for 24 months after implant loading. The primary outcome measure is non-inferiority of implant success rate of the experimental group compared to the control group. The secondary outcome measures encompass clinical, technical and subjective variables. The study was funded by the Deutsche Forschungsgemeinschaft (German research foundation, KE 477/8-1). Discussion This multi-center clinical trial will give information on the ability of a single median implant to retain a complete mandibular denture when immediately loaded. If viable, this treatment option will strongly improve everyday dental practice. Trial registration The trial has been registered at Deutsches Register Klinischer Studien (German register of clinical trials) under DRKS-ID: DRKS00003730 since 23 August 2012. (http://www.germanctr.de). PMID:24884848

Antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease.

PubMed

Martí-Carvajal, Arturo J; Solà, Ivan

2015-06-09

Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. People with liver disease frequently have haemostatic abnormalities such as hyperfibrinolysis. Therefore, antifibrinolytic amino acids have been proposed to be used as supplementary interventions alongside any of the primary treatments for upper gastrointestinal bleeding in people with liver diseases. This is an update of this Cochrane review. To assess the beneficial and harmful effects of antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease. We searched The Cochrane Hepato-Biliary Controlled Trials Register (February 2015), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2 of 12, 2015), MEDLINE (Ovid SP) (1946 to February 2015), EMBASE (Ovid SP) (1974 to February 2015), Science Citation Index EXPANDED (1900 to February 2015), LILACS (1982 to February 2015), World Health Organization Clinical Trials Search Portal (accessed 26 February 2015), and the metaRegister of Controlled Trials (accessed 26 February 2015). We scrutinised the reference lists of the retrieved publications. Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. Observational studies for assessment of harms. We planned to summarise data from randomised clinical trials using standard Cochrane methodologies and assessed according to the GRADE approach. We found no randomised clinical trials assessing antifibrinolytic amino acids for treating upper gastrointestinal bleeding in people with acute or chronic liver disease. We did not identify quasi-randomised, historically controlled, or observational studies in which we could assess harms. This updated Cochrane review identified no randomised clinical trials assessing the benefits and harms of antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease. The benefits and harms of antifibrinolytic amino acids need to be tested in randomised clinical trials. Unless randomised clinical trials are conducted to assess the trade-off between benefits and harms, we cannot recommend or refute antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver diseases.

Comparison of Registered and Reported Outcomes in Randomized Clinical Trials Published in Anesthesiology Journals.

PubMed

Jones, Philip M; Chow, Jeffrey T Y; Arango, Miguel F; Fridfinnson, Jason A; Gai, Nan; Lam, Kevin; Turkstra, Timothy P

2017-10-01

Randomized clinical trials (RCTs) provide high-quality evidence for clinical decision-making. Trial registration is one of the many tools used to improve the reporting of RCTs by reducing publication bias and selective outcome reporting bias. The purpose of our study is to examine whether RCTs published in the top 6 general anesthesiology journals were adequately registered and whether the reported primary and secondary outcomes corresponded to the originally registered outcomes. Following a prespecified protocol, an electronic database was used to systematically screen and extract data from RCTs published in the top 6 general anesthesiology journals by impact factor (Anaesthesia, Anesthesia & Analgesia, Anesthesiology, British Journal of Anaesthesia, Canadian Journal of Anesthesia, and European Journal of Anaesthesiology) during the years 2007, 2010, 2013, and 2015. A manual search of each journal's Table of Contents was performed (in duplicate) to identify eligible RCTs. An adequately registered trial was defined as being registered in a publicly available trials registry before the first patient being enrolled with an unambiguously defined primary outcome. For adequately registered trials, the outcomes registered in the trial registry were compared with the outcomes reported in the article, with outcome discrepancies documented and analyzed by the type of discrepancy. During the 4 years studied, there were 860 RCTs identified, with 102 RCTs determined to be adequately registered (12%). The proportion of adequately registered trials increased over time, with 38% of RCTs being adequately registered in 2015. The most common reason in 2015 for inadequate registration was registering the RCT after the first patient had already been enrolled. Among adequately registered trials, 92% had at least 1 primary or secondary outcome discrepancy. In 2015, 42% of RCTs had at least 1 primary outcome discrepancy, while 90% of RCTs had at least 1 secondary outcome discrepancy. Despite trial registration being an accepted best practice, RCTs published in anesthesiology journals have a high rate of inadequate registration. While mandating trial registration has increased the proportion of adequately registered trials over time, there is still an unacceptably high proportion of inadequately registered RCTs. Among adequately registered trials, there are high rates of discrepancies between registered and reported outcomes, suggesting a need to compare a published RCT with its trial registry entry to be able to fully assess the quality of the study. If clinicians base their decisions on evidence distorted by primary outcome switching, patient care could be negatively affected.

[Features of Clinical Register of Chinese Medicine and Pharmacy Based on ClinicalTrials.gov. (USA)].

PubMed

Lu, Peng-fei; Liao, Xing; Xie, Yan-ming; Wang, Zhi-guo

2015-11-01

In recent 10 years, clinical trials of Chinese medicine and pharmacy (cMP) at clinicalTrials.gov.(USA) are gradually increasing. In order to analyze features of CMP clinical register, ClinicalTrials.gov register database were comprehensively retrieved in this study. Included clinical trials were input one item after another using EXCEL. A final of 348 CMP clinical trials were included. Results showed that China occupied the first place in CMP clinical register, followed by USA. CMP clinical trials, sponsored mainly by colleges/universities and hospitals, mostly covered interventional studies on evaluating safety/effectiveness of CMP. The proportions of studies, sponsored by mainland China and companies, recruitment trials and multi-center clinical trials in interventional trials were increasing. The proportions of studies sponsored by Hong Kong and Taiwan, research completed trials, unclear research status, phase III clinical trials, and published research trials in interventional trials were decreasing. Published ratios of CMP clinical trials were quite low. There were more missing types and higher proportions in trial register information.

Pharmacologic intervention for retained placenta: a systematic review and meta-analysis.

PubMed

Duffy, James M N; Mylan, Sophie; Showell, Marian; Wilson, Matthew J A; Khan, Khalid S

2015-03-01

To assess the effectiveness and safety of pharmacologic interventions for the treatment of retained placenta (when the placenta remains undelivered after 30 minutes of active management of the third stage of labor). We searched: 1) Cochrane Central Register of Controlled Trials (CENTRAL), 2) Cochrane Pregnancy and Childbirth Group's Trials Register, 3) EMBASE, and 4) MEDLINE from inception to June 2014. Randomized controlled trials comparing a pharmacologic intervention(s) with a placebo for the treatment of retained placenta were included. Sixteen randomized controlled trials, including 1,683 participants, were included. Study characteristics and quality were recorded. The meta-analysis was based on random-effects methods for pooled data. There were no statistically significant differences in the requirement to perform manual removal of a placenta in patients treated with oxytocin (55% compared with 60%; relative risk [RR] 0.86, 95% confidence interval [CI] 0.73-1.02; 10 randomized controlled trials [RCTs]), prostaglandins (44% compared with 55%; RR 0.82, 95% CI 0.58-1.15; four RCTs), nitroglycerin (85% compared with 80%; RR 1.06, 95% CI 0.80-1.41; one RCT), or oxytocin and nitroglycerin (52% compared with 79%; RR 0.23, 95% CI 0.01-8.48; two RCTs) compared with placebo. There was limited reporting of secondary outcomes. As opposed to the use of oxytocin as part of the active management of the third stage of labor that has been shown to diminish bleeding in the third stage, once the diagnosis of retained placenta has been made, no pharmacologic treatment has been shown to be effective. When retained placenta is diagnosed, immediate manual removal of the placenta should be considered. PROSPERO International Prospective Register of Systematic Reviews, http://www.crd.york.ac.uk/PROSPERO/, CRD42014010641.

Randomized clinical trials in orthodontics are rarely registered a priori and often published late or not at all.

PubMed

Papageorgiou, Spyridon N; Antonoglou, Georgios N; Sándor, George K; Eliades, Theodore

2017-01-01

A priori registration of randomized clinical trials is crucial to the transparency and credibility of their findings. Aim of this study was to assess the frequency with which registered and completed randomized trials in orthodontics are published. We searched ClinicalTrials.gov and ISRCTN for registered randomized clinical trials in orthodontics that had been completed up to January 2017 and judged the publication status and date of registered trials using a systematic protocol. Statistical analysis included descriptive statistics, chi-square or Fisher exact tests, and Kaplan-Meier survival estimates. From the 266 orthodontic trials registered up to January 2017, 80 trials had been completed and included in the present study. Among these 80 included trials, the majority (76%) were registered retrospectively, while only 33 (41%) were published at the time. The median time from completion to publication was 20.1 months (interquartile range: 9.1 to 31.6 months), while survival analysis indicated that less than 10% of the trials were published after 5 years from their completion. Finally, 22 (28%) of completed trials remain unpublished even after 5 years from their completion. Publication rates of registered randomized trials in orthodontics remained low, even 5 years after their completion date.

Randomized clinical trials in orthodontics are rarely registered a priori and often published late or not at all

PubMed Central

Antonoglou, Georgios N.; Sándor, George K.; Eliades, Theodore

2017-01-01

A priori registration of randomized clinical trials is crucial to the transparency and credibility of their findings. Aim of this study was to assess the frequency with which registered and completed randomized trials in orthodontics are published. We searched ClinicalTrials.gov and ISRCTN for registered randomized clinical trials in orthodontics that had been completed up to January 2017 and judged the publication status and date of registered trials using a systematic protocol. Statistical analysis included descriptive statistics, chi-square or Fisher exact tests, and Kaplan-Meier survival estimates. From the 266 orthodontic trials registered up to January 2017, 80 trials had been completed and included in the present study. Among these 80 included trials, the majority (76%) were registered retrospectively, while only 33 (41%) were published at the time. The median time from completion to publication was 20.1 months (interquartile range: 9.1 to 31.6 months), while survival analysis indicated that less than 10% of the trials were published after 5 years from their completion. Finally, 22 (28%) of completed trials remain unpublished even after 5 years from their completion. Publication rates of registered randomized trials in orthodontics remained low, even 5 years after their completion date. PMID:28777820

Insufflation with Humidified and Heated Carbon Dioxide in Short-Term Laparoscopy: A Double-Blinded Randomized Controlled Trial

PubMed Central

Herrmann, Anja; De Wilde, Rudy Leon

2015-01-01

Background. We tested the hypothesis that warm-humidified carbon dioxide (CO2) insufflation would reduce postoperative pain and morphine requirement compared to cold-dry CO2 insufflation. Methods. A double-blinded, randomized, controlled trial was conducted to compare warm, humidified CO2 and cold-dry CO2. Patients with benign uterine diseases were randomized to either treatment (n = 48) or control (n = 49) group during laparoscopically assisted vaginal hysterectomy. Primary endpoints of the study were rest pain, movement pain, shoulder-tip pain, and cough pain at 2, 4, 6, 24, and 48 hours postoperatively, measured by visual analogue scale. Secondary outcomes were morphine consumption, rejected boli, temperature change, recovery room stay, and length of hospital stay. Results. There were no significant differences in all baseline characteristics. Shoulder-tip pain at 6 h postoperatively was significantly reduced in the intervention group. Pain at rest, movement pain, and cough pain did not differ. Total morphine consumption and rejected boli at 24 h postoperatively were significantly higher in the control group. Temperature change, recovery room stay, and length of hospital were similar. Conclusions. Warm, humidified insufflation gas significantly reduces postoperative shoulder-tip pain as well as morphine demand. This trial is registered with Clinical Trial Registration Number   DRKS00003853 (German Clinical Trials Register (DRKS)). PMID:25722977

Singing for children and adults with bronchiectasis.

PubMed

Irons, Jung Yoon; Kenny, Dianna Theadora; Chang, Anne B

2010-02-17

Bronchiectasis is a common respiratory disease, especially in developing countries. Its cause varies from chronic infection to rare immune deficiencies. Bronchiectasis can be present with other respiratory diseases, such as chronic obstructive pulmonary disease (COPD). People with bronchiectasis may suffer from chronic cough, fatigue, shortness of breath, chest pain and coughing up blood. Their lung function may decline with time. These can also have a negative impact on their quality of life. Thus, a holistic management is needed to provide treatment and support. Therapies which include breathing manoeuvres, such as singing, may have health benefits for respiratory function and psychological well being. To evaluate the effects of a singing intervention as a therapy on the quality of life, morbidity, respiratory muscle strength and pulmonary function of children and adults with bronchiectasis. We searched the Cochrane Airways Group (CAG) trials register, the Cochrane Central Register of Controlled Trials, major allied complementary databases, and clinical trials registers. Professional organisations and individuals were also contacted. CAG performed searches in February, and additional searches were carried out in June 2009. Randomised controlled trials in which singing (as an intervention) is compared with either a sham intervention or no singing in patients with bronchiectasis. Two authors independently reviewed the titles, abstracts and citations to assess potential relevance for full review. No eligible trials were identified and thus no data were available for analysis. No meta-analysis could be performed. In the absence of data, we cannot draw any conclusion to support or refute the adoption of singing as an intervention for people with bronchiectasis. Given the simplicity of the potentially beneficial intervention, future randomised controlled trials are required to evaluate singing therapy for people with bronchiectasis.

Comparison of an interactive with a didactic educational intervention for improving the evidence-based practice knowledge of occupational therapists in the public health sector in South Africa: a randomised controlled trial

PubMed Central

2014-01-01

Background Despite efforts to identify effective interventions to implement evidence-based practice (EBP), uncertainty remains. Few existing studies involve occupational therapists or resource-constrained contexts. This study aimed to determine whether an interactive educational intervention (IE) was more effective than a didactic educational intervention (DE) in improving EBP knowledge, attitudes and behaviour at 12 weeks. Methods A matched pairs design, randomised controlled trial was conducted in the Western Cape of South Africa. Occupational therapists employed by the Department of Health were randomised using matched-pair stratification by type (clinician or manager) and knowledge score. Allocation to an IE or a DE was by coin-tossing. A self-report questionnaire (measuring objective knowledge and subjective attitudes) and audit checklist (measuring objective behaviour) were completed at baseline and 12 weeks. The primary outcome was EBP knowledge at 12 weeks while secondary outcomes were attitudes and behaviour at 12 weeks. Data collection occurred at participants’ places of employment. Audit raters were blinded, but participants and the provider could not be blinded. Results Twenty-one of 28 pairs reported outcomes, but due to incomplete data for two participants, 19 pairs were included in the analysis. There was a median increase of 1.0 points (95% CI = -4.0, 1.0) in the IE for the primary outcome (knowledge) compared with the DE, but this difference was not significant (P = 0.098). There were no significant differences on any of the attitude subscale scores. The median 12-week audit score was 8.6 points higher in the IE (95% CI = -7.7, 27.0) but this was not significant (P = 0.196). Within-group analyses showed significant increases in knowledge in both groups (IE: T = 4.0, P <0.001; DE: T = 12.0, P = 0.002) but no significant differences in attitudes or behaviour. Conclusions The results suggest that the interventions had similar outcomes at 12 weeks and that the interactive component had little additional effect. Trial registration Pan African Controlled Trials Register PACTR201201000346141, registered 31 January 2012. Clinical Trials NCT01512823, registered 1 February 2012. South African National Clinical Trial Register DOH2710093067, registered 27 October 2009. The first participants were randomly assigned on 16 July 2008. PMID:24916176

Four layer bandage compared with short stretch bandage for venous leg ulcers: systematic review and meta-analysis of randomised controlled trials with data from individual patients

PubMed Central

Tierney, Jayne; Cullum, Nicky; Bland, J Martin; Franks, Peter J; Mole, Trevor; Scriven, Mark

2009-01-01

Objective To compare the effectiveness of two types of compression treatment (four layer bandage and short stretch bandage) in people with venous leg ulceration. Design Systematic review and meta-analysis of patient level data. Data sources Electronic databases (the Cochrane Central Register of Controlled Trials, the Cochrane Wounds Group Specialised Register, Medline, Embase, CINAHL, and National Research Register) and reference lists of retrieved articles searched to identify relevant trials and primary investigators. Primary investigators of eligible trials were invited to contribute raw data for re-analysis. Review methods Randomised controlled trials of four layer bandage compared with short stretch bandage in people with venous leg ulceration were eligible for inclusion. The primary outcome for the meta-analysis was time to healing. Cox proportional hazards models were run to compare the methods in terms of time to healing with adjustment for independent predictors of healing. Secondary outcomes included incidence and number of adverse events per patient. Results Seven eligible trials were identified (887 patients), and patient level data were retrieved for five (797 patients, 90% of known randomised patients). The four layer bandage was associated with significantly shorter time to healing: hazard ratio (95% confidence interval) from multifactorial model based on five trials was 1.31 (1.09 to 1.58), P=0.005. Larger ulcer area at baseline, more chronic ulceration, and previous ulceration were all independent predictors of delayed healing. Data from two trials showed no evidence of a difference in adverse event profiles between the two bandage types. Conclusions Venous leg ulcers in patients treated with four layer bandages heal faster, on average, than those of people treated with the short stretch bandage. Benefits were consistent across patients with differing prognostic profiles. PMID:19376798

The FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: statistical and health economic analysis plan for the trials and for the individual patient data meta-analysis.

PubMed

Graham, Catriona; Lewis, Steff; Forbes, John; Mead, Gillian; Hackett, Maree L; Hankey, Graeme J; Gommans, John; Nguyen, Huy Thang; Lundström, Erik; Isaksson, Eva; Näsman, Per; Rudberg, Ann-Sofie; Dennis, Martin

2017-12-28

Small trials have suggested that fluoxetine may improve neurological recovery from stroke. FOCUS, AFFINITY and EFFECTS are a family of investigator-led, multicentre, parallel group, randomised, placebo-controlled trials which aim to determine whether the routine administration of fluoxetine (20 mg daily) for six months after an acute stroke improves patients' functional outcome. The core protocol for the three trials has been published (Mead et al., Trials 20:369, 2015). The trials include patients aged 18 years and older with a clinical diagnosis of stroke and persisting focal neurological deficits at randomisation 2-15 days after stroke onset. Patients are randomised centrally via each trials' web-based randomisation system using a common minimisation algorithm. Patients are allocated fluoxetine 20 mg once daily or matching placebo capsules for six months. The primary outcome measure is the modified Rankin scale (mRS) at six months. Secondary outcomes include: living circumstances; the Stroke Impact Scale; EuroQol (EQ5D-5 L); the vitality subscale of the 36-Item Short Form Health Survey (SF36); diagnosis of depression; adherence to medication; serious adverse events including death and recurrent stroke; and resource use at six and 12 months and the mRS at 12 months. Minor variations have been tailored to the national setting in the UK (FOCUS), Australia, New Zealand and Vietnam (AFFINITY) and Sweden (EFFECTS). Each trial is run and funded independently and will report its own results. A prospectively planned individual patient data meta-analysis of all three trials will provide the most precise estimate of the overall effect and establish whether any effects differ between trials or subgroups. This statistical analysis plan describes the core analyses for all three trials and that for the individual patient data meta-analysis. Recruitment and follow-up in the FOCUS trial is expected to be completed by the end of 2018. AFFINITY and EFFECTS are likely to complete follow-up in 2020. FOCUS: ISRCTN , ISRCTN83290762 . Registered on 23 May 2012. EudraCT, 2011-005616-29. Registered on 3 February 2012. Australian New Zealand Clinical Trials Registry, ACTRN12611000774921 . Registered on 22 July 2011. ISRCTN , ISRCTN13020412 . Registered on 19 December 2014. Clinicaltrials.gov, NCT02683213 . Registered on 2 February 2016. EudraCT, 2011-006130-16 . Registered on 8 August 2014.

Anticonvulsants or Antidepressants in Combination Pharmacotherapy for Treatment of Neuropathic Pain in Cancer Patients: A Systematic Review and Meta-analysis.

PubMed

Guan, Jia; Tanaka, Shiro; Kawakami, Koji

2016-08-01

To investigate the efficacy of anticonvulsants or antidepressants in combination pharmacotherapy for treatment of neuropathic pain in cancer patients. We systematically searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the metaRegister of Controlled Trials for randomized controlled trials that compared anticonvulsants or antidepressants in combination pharmacotherapy (experimental group) with treatments without anticonvulsants or antidepressants (control group) for neuropathic pain in cancer patients. Risk of bias was evaluated in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was a mean difference (MD) in change in global pain analyzed by a random-effects model. Eight trials met the inclusion criteria with a total of 1359 participants of whom 698 received an experimental intervention. The MD in change in global pain suggested a favorable association with anticonvulsants or antidepressants in combination pharmacotherapy compared with control groups (MD, -0.41; 95% confidence interval, -0.70 to -0.12) with no heterogeneity across trials (I=0%). The MD in change estimated in all sensitivity analyses ranged from -0.36 to -0.47, suggesting that these effects were consistent across different study designs and statistical assumptions. Anticonvulsants or antidepressants in combination pharmacotherapy reduce neuropathic pain in cancer patients compared with treatments without anticonvulsants or antidepressants. Limited evidence precludes a recommendation on specific adjuvants in combination pharmacotherapy.

RandomizEd controlled trial for pre-operAtive dose-escaLation BOOST in locally advanced rectal cancer (RECTAL BOOST study): study protocol for a randomized controlled trial.

PubMed

Burbach, J P Maarten; Verkooijen, Helena M; Intven, Martijn; Kleijnen, Jean-Paul J E; Bosman, Mirjam E; Raaymakers, Bas W; van Grevenstein, Wilhelmina M U; Koopman, Miriam; Seravalli, Enrica; van Asselen, Bram; Reerink, Onne

2015-02-22

Treatment for locally advanced rectal cancer (LARC) consists of chemoradiation therapy (CRT) and surgery. Approximately 15% of patients show a pathological complete response (pCR). Increased pCR-rates can be achieved through dose escalation, thereby increasing the number patients eligible for organ-preservation to improve quality of life (QoL). A randomized comparison of 65 versus 50Gy with external-beam radiation alone has not yet been performed. This trial investigates pCR rate, clinical response, toxicity, QoL and (disease-free) survival in LARC patients treated with 65Gy (boost + chemoradiation) compared with 50Gy standard chemoradiation (sCRT). This study follows the 'cohort multiple randomized controlled trial' (cmRCT) design: rectal cancer patients are included in a prospective cohort that registers clinical baseline, follow-up, survival and QoL data. At enrollment, patients are asked consent to offer them experimental interventions in the future. Eligible patients-histologically confirmed LARC (T3NxM0 <1 mm from mesorectal fascia, T4NxM0 or TxN2M0) located ≤10 cm from the anorectal transition who provided consent for experimental intervention offers-form a subcohort (n = 120). From this subcohort, a random sample is offered the boost prior to sCRT (n = 60), which they may accept or refuse. Informed consent is signed only after acceptance of the boost. Non-selected patients in the subcohort (n = 60) undergo sCRT alone and are not notified that they participate in the control arm until the trial is completed. sCRT consists of 50Gy (25 × 2Gy) with concomitant capecitabine. The boost (without chemotherapy) is given prior to sCRT and consists of 15 Gy (5 × 3Gy) delivered to the gross tumor volume (GTV). The primary endpoint is pCR (TRG 1). Secondary endpoints include acute grade 3-4 toxicity, good pathologic response (TRG 1-2), clinical response, surgical complications, QoL and (disease-free) survival. Data is analyzed by intention to treat. The boost is delivered prior to sCRT so that GTV adjustment for tumor shrinkage during sCRT is not necessary. Small margins also aim to limit irradiation of healthy tissue. The cmRCT design provides opportunity to overcome common shortcomings of classic RCTs, such as slow recruitment, disappointment-bias in control arm patients and poor generalizability. The Netherlands Trials Register NL46051.041.13. Registered 22 August 2013. ClinicalTrials.gov NCT01951521 . Registered 18 September 2013.

Using ClinicalTrials.gov to Supplement Information in Ophthalmology Conference Abstracts about Trial Outcomes: A Comparison Study

PubMed Central

Scherer, Roberta W.; Huynh, Lynn; Ervin, Ann-Margret; Dickersin, Kay

2015-01-01

Background Including results from unpublished randomized controlled trials (RCTs) in a systematic review may ameliorate the effect of publication bias in systematic review results. Unpublished RCTs are sometimes described in abstracts presented at conferences, included in trials registers, or both. Trial results may not be available in a trials register and abstracts describing RCT results often lack study design information. Complementary information from a trials register record may be sufficient to allow reliable inclusion of an unpublished RCT only available as an abstract in a systematic review. Methods We identified 496 abstracts describing RCTs presented at the 2007 to 2009 Association for Research in Vision and Ophthalmology (ARVO) meetings; 154 RCTs were registered in ClinicalTrials.gov. Two persons extracted verbatim primary and non-primary outcomes reported in the abstract and ClinicalTrials.gov record. We compared each abstract outcome with all ClinicalTrials.gov outcomes and coded matches as complete, partial, or no match. Results We identified 800 outcomes in 152 abstracts (95 primary [51 abstracts] and 705 [141 abstracts] non-primary outcomes). No outcomes were reported in 2 abstracts. Of 95 primary outcomes, 17 (18%) agreed completely, 53 (56%) partially, and 25 (26%) had no match with a ClinicalTrials.gov primary or non-primary outcome. Among 705 non-primary outcomes, 56 (8%) agreed completely, 205 (29%) agreed partially, and 444 (63%) had no match with a ClinicalTrials.gov primary or non-primary outcome. Among the 258 outcomes partially agreeing, we found additional information on the time when the outcome was measured more often in ClinicalTrials.gov than in the abstract (141/258 (55%) versus 55/258 (21%)). We found no association between the presence of non-matching “new” outcomes and year of registration, time to registry update, industry sponsorship, or multi-center status. Conclusion Conference abstracts may be a valuable source of information about results for outcomes of unpublished RCTs that have been registered in ClinicalTrials.gov. Complementary additional descriptive information may be present for outcomes reported in both sources. However, ARVO abstract authors also present outcomes not reported in ClinicalTrials.gov and these may represent analyses not originally planned. PMID:26107924

Short- and long-term risks of cardiovascular disease following radiotherapy in rectal cancer in four randomized controlled trials and a population-based register.

PubMed

Chen, Lingjing; Eloranta, Sandra; Martling, Anna; Glimelius, Ingrid; Neovius, Martin; Glimelius, Bengt; Smedby, Karin E

2018-03-01

A population-based cohort and four randomized trials enriched with long-term register data were used to clarify if radiotherapy in combination with rectal cancer surgery is associated with increased risks of cardiovascular disease (CVD). We identified 14,901 rectal cancer patients diagnosed 1995-2009 in Swedish nationwide registers, of whom 9227 were treated with preoperative radiotherapy. Also, we investigated 2675 patients with rectal cancer previously randomized to preoperative radiotherapy or not followed by surgery in trials conducted 1980-1999. Risks of CVD overall and subtypes were estimated based on prospectively recorded hospital visits during relapse-free follow-up using multivariable Cox regression. Maximum follow-up was 18 and 33 years in the register and trials, respectively. We found no association between preoperative radiotherapy and overall CVD risk in the register (Incidence Rate Ratio, IRR = 0.99, 95% confidence interval (CI) 0.92-1.06) or in the pooled trials (IRR = 1.07, 95% CI 0.93-1.24). We noted an increased risk of venous thromboembolism among irradiated patients in both cohorts (IRR register  = 1.41, 95% CI 1.15-2.72; IRR trials  = 1.41, 95% CI 0.97-2.04), that remained during the first 6 months following surgery among patients treated 2006-2009, after the introduction of antithrombotic treatment (IRR 6 months  = 2.30, 95% CI 1.01-5.21). However, the absolute rate difference of venous thromboembolism attributed to RT was low (10 cases per 1000 patients and year). Preoperative radiotherapy did not affect rectal cancer patients' risk of CVD overall. Although an excess risk of short-term venous thromboembolism was noted, the small increase in absolute numbers does not call for general changes in routine prophylactic treatment, but might do so for patients already at high risk of venous thromboembolism. Copyright © 2017 Elsevier B.V. All rights reserved.

Inadvertent P-hacking among trials and systematic reviews of the effect of progestogens in pregnancy? A systematic review and meta-analysis.

PubMed

Prior, M; Hibberd, R; Asemota, N; Thornton, J G

2017-06-01

Progestogens have been evaluated in numerous trials and meta-analyses, many of which concluded they were effective. However, two large trials PROMISE and OPPTIMUM have recently concluded that progesterone was ineffective. This raises the possibility that earlier studies and reviews had been biased by either selective publication or selective choice of outcomes, so called "P-hacking". To compare the findings all progestogen trials and systematic reviews with those of trials with pre-registered primary outcomes which avoided selective outcome reporting. Search of PubMed, the Cochrane Library and trial registries. Registration PROSPERO CRD42016035303. Systematic reviews of randomised trials comparing progestogen with placebo in pregnancy and the individual trials included in those reviews. The subset of trials reporting a pre-registered primary outcome were compared with the totality of trials and reviews. For reviews all outcomes were included. For individual trials all outcomes reported in the systematic reviews were included. For the comparison group we recorded the registered primary outcome from trials that were either registered before they started, or registered during the recruitment phase and also double blind. Nineteen of twenty-nine meta-analyses concluded that progestogens were effective. Twenty-two trials reported their pre-registered primary outcomes. There was no effect of progesterone on primary registered dichotomous outcome RR 1.00 (95% CI 0.94-1.07). Only one of the 22 showed a nominally statistically significant benefit. When evaluated in registered double-blind trials with analysis restricted to predefined primary outcomes, progestational agents in pregnancy are ineffective. Progestogens to prevent pregnancy loss, an example of P-hacking. © 2017 Royal College of Obstetricians and Gynaecologists.

Mirror therapy for improving motor function after stroke.

PubMed

Thieme, Holm; Mehrholz, Jan; Pohl, Marcus; Behrens, Johann; Dohle, Christian

2013-01-01

This systematic review summarizes the effectiveness of mirror therapy for improving motor function, activities of daily living, pain, and visuospatial neglect in patients after stroke. We searched the Cochrane Stroke Group’s Trials Register (June 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (1950 to June 2011), EMBASE (1980 to June 2011), CINAHL (1982 to June 2011), AMED (1985 to June 2011), PsycINFO (1806 to June 2011), and PEDro (June 2011). We also handsearched relevant conference proceedings, trials, and research registers; checked reference lists; and contacted trialists, researchers, and experts in our field of study. We included randomized controlled trials and randomized crossover trials comparing mirror therapy with any control intervention for patients after stroke. Two review authors independently selected trials based on the inclusion criteria, documented the methodological quality of studies, and extracted data. The primary outcome was motor function. We analyzed the results as standardized mean differences (SMDs) for continuous variables. We included 14 studies with a total of 567 participants, which compared mirror therapy with other interventions. When compared with all other interventions, mirror therapy was found to have a significant effect on motor function (postintervention data: SMD 0.61; 95% CI 0.22 to 1.0; P=0.002; change scores: SMD 1.04; 95% CI 0.57 to 1.51; P<0.0001) ; Figure). However, effects on motor function are influenced by the type of control intervention. Additionally, mirror therapy was found to improve activities of daily living (SMD 0.33; 95% CI 0.05 to 0.60; P=0.02). We found a significant positive effect on pain (SMD −1.10; 95% CI −2.10 to −0.09; P=0.03), which is influenced by patient population. We found limited evidence for improving visuospatial neglect (SMD 1.22; 95% CI 0.24 to 2.19; P=0.01). The effects on motor function were stable at follow-up assessment after 6 months.

Increasing chlamydia screening tests in general practice: a modified Zelen prospective Cluster Randomised Controlled Trial evaluating a complex intervention based on the Theory of Planned Behaviour.

PubMed

McNulty, Cliodna A M; Hogan, Angela H; Ricketts, Ellie J; Wallace, Louise; Oliver, Isabel; Campbell, Rona; Kalwij, Sebastian; O'Connell, Elaine; Charlett, Andre

2014-05-01

To determine if a structured complex intervention increases opportunistic chlamydia screening testing of patients aged 15-24 years attending English general practitioner (GP) practices. A prospective, Cluster Randomised Controlled Trial with a modified Zelen design involving 160 practices in South West England in 2010. The intervention was based on the Theory of Planned Behaviour (TPB). It comprised of practice-based education with up to two additional contacts to increase the importance of screening to GP staff and their confidence to offer tests through skill development (including videos). Practical resources (targets, posters, invitation cards, computer reminders, newsletters including feedback) aimed to actively influence social cognitions of staff, increasing their testing intention. Data from 76 intervention and 81 control practices were analysed. In intervention practices, chlamydia screening test rates were 2.43/100 15-24-year-olds registered preintervention, 4.34 during intervention and 3.46 postintervention; controls testing rates were 2.61/100 registered patients prior intervention, 3.0 during intervention and 2.82 postintervention. During the intervention period, testing in intervention practices was 1.76 times as great (CI 1.24 to 2.48) as controls; this persisted for 9 months postintervention (1.57 times as great, CI 1.27 to 2.30). Chlamydia infections detected increased in intervention practices from 2.1/1000 registered 15-24-year-olds prior intervention to 2.5 during the intervention compared with 2.0 and 2.3/1000 in controls (Estimated Rate Ratio intervention versus controls 1.4 (CI 1.01 to 1.93). This complex intervention doubled chlamydia screening tests in fully engaged practices. The modified Zelen design gave realistic measures of practice full engagement (63%) and efficacy of this educational intervention in general practice; it should be used more often. The trial was registered on the UK Clinical Research Network Study Portfolio database. UKCRN number 9722.

Quality of registration for clinical trials published in emergency medicine journals.

PubMed

Jones, Christopher W; Platts-Mills, Timothy F

2012-10-01

In 2005, the International Committee of Medical Journal Editors established clinical trial registration as a requirement for articles submitted to member journals, with the goal of improving the transparency of clinical research. The objective of this study is to characterize the registration of clinical trials published in emergency medicine journals. Randomized trials involving human subjects and published between June 1, 2008, and May 31, 2011 in the 5 emergency medicine journals with the highest impact factors were included. We assessed the clarity of registered primary outcomes, timing of registration relative to patient enrollment, and consistency between registered and published outcomes. Of the 123 trials included, registry entries were identified for 57 (46%). Of the 57 registered studies, 45 (79%) were registered after the initiation of subject enrollment, 9 (16%) had registered outcomes that were unclear, and 26 (46%) had discrepancies between registered and published outcomes. Only 5 studies were registered before patient enrollment with a clear primary outcome that was consistent with the published primary outcome. Annals of Emergency Medicine was the only journal in which the majority of trials were registered. Current compliance with clinical trial registration guidelines is poor among trials published in emergency medicine journals. Copyright © 2012. Published by Mosby, Inc.

Adhesives for fixed orthodontic brackets.

PubMed

Mandall, Nicky A; Hickman, Joy; Macfarlane, Tatiana V; Mattick, Rye Cr; Millett, Declan T; Worthington, Helen V

2018-04-09

Bonding of orthodontic brackets to teeth is important to enable effective and efficient treatment with fixed appliances. The problem is bracket failure during treatment which increases operator chairside time and lengthens treatment time. A prolonged treatment is likely to increase the oral health risks of orthodontic treatment with fixed appliances one of which is irreversible enamel decalcification. This is an update of the Cochrane Review first published in 2003. A new full search was conducted on 26 September 2017 but no new studies were identified. We have only updated the search methods section in this new version. The conclusions of this Cochrane Review remain the same. To evaluate the effects of different orthodontic adhesives for bonding. Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 26 September 2017), the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8) in the Cochrane Library (searched 26 September 2017), MEDLINE Ovid (1946 to 26 September 2017), and Embase Ovid (1980 to 26 September 2017). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Trials were selected if they met the following criteria: randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing two different adhesive groups. Participants were patients with fixed orthodontic appliances. The interventions were adhesives that bonded stainless steel brackets to all teeth except the molars. The primary outcome was debond or bracket failure. Data were recorded on decalcification as a secondary outcome, if present. Information regarding methods, participants, interventions, outcome measures and results were extracted in duplicate by pairs of review authors. Since the data were not presented in a form that was amenable to meta-analysis, the results of the review are presented in narrative form only. Three trials satisfied the inclusion criteria. A chemical cured composite was compared with a light cured composite (one trial), a conventional glass ionomer cement (one trial) and a polyacid-modified resin composite (compomer) (one trial). The quality of the trial reports was generally poor. There is no clear evidence on which to make a clinical decision of the type of orthodontic adhesive to use.

Interventions for treating acute bleeding episodes in people with acquired hemophilia A.

PubMed

Zeng, Yan; Zhou, Ruiqing; Duan, Xin; Long, Dan; Yang, Songtao

2014-08-28

Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation factor VIII (FVIII). In most cases, bleeding episodes are spontaneous and severe at presentation. The optimal hemostatic therapy is controversial. To determine the efficacy of hemostatic therapies for acute bleeds in people with acquired hemophilia A; and to compare different forms of therapy for these bleeds. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 4) and MEDLINE (Ovid) (1948 to 30 April 2014). We searched the conference proceedings of the: American Society of Hematology; European Hematology Association; International Society on Thrombosis and Haemostasis (ISTH); and the European Association for Haemophilia and Allied Disorders (EAHAD) (from 2000 to 30 April 2014). In addition to this we searched clinical trials registers. All randomised controlled trials and quasi-randomised trials of hemostatic therapies for people with acquired hemophilia A, with no restrictions on gender, age or ethnicity. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. No randomised clinical trials of hemostatic therapies for acquired hemophilia A were found. Thus, we are not able to draw any conclusions or make any recommendations on the optimal hemostatic therapies for acquired hemophilia A based on the highest quality of evidence. GIven that carrying out randomized controlled trials in this field is a complex task, the authors suggest that, while planning randomised controlled trials in which patients can be enrolled, clinicians treating the disease continue to base their choices on alternative, lower quality sources of evidence, which hopefully, in the future, will also be appraised and incorporated in a Cochrane Review.

Disposable surgical face masks for preventing surgical wound infection in clean surgery.

PubMed

Lipp, Allyson; Edwards, Peggy

2014-02-17

Surgical face masks were originally developed to contain and filter droplets containing microorganisms expelled from the mouth and nasopharynx of healthcare workers during surgery, thereby providing protection for the patient. However, there are several ways in which surgical face masks could potentially contribute to contamination of the surgical wound, e.g. by incorrect wear or by leaking air from the side of the mask due to poor string tension. To determine whether disposable surgical face masks worn by the surgical team during clean surgery prevent postoperative surgical wound infection. We searched The Cochrane Wounds Group Specialised Register on 23 October 2013; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. Randomised controlled trials (RCTs) and quasi-randomised controlled trials comparing the use of disposable surgical masks with the use of no mask. Two review authors extracted data independently. Three trials were included, involving a total of 2113 participants. There was no statistically significant difference in infection rates between the masked and unmasked group in any of the trials. From the limited results it is unclear whether the wearing of surgical face masks by members of the surgical team has any impact on surgical wound infection rates for patients undergoing clean surgery.

Negative pressure wound therapy for partial-thickness burns.

PubMed

Dumville, Jo C; Munson, Christopher; Christie, Janice

2014-12-15

A burn wound is a complex and evolving injury, with both local and systemic consequences. Burn treatments include a variety of dressings, as well as newer strategies, such as negative pressure wound therapy (NPWT), which, by means of a suction force that drains excess fluids from the burn, tries to promote the wound healing process and minimise progression of the burn wound. To assess the effectiveness of NPWT for people with partial-thickness burns. We searched the Cochrane Wounds Group Specialised Register (searched 04 September 2014); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 8). All randomised controlled trials (RCTs) and controlled clinical trials (CCTs) that evaluated the safety and effectiveness of NPWT for partial-thickness burns. Two review authors used standardised forms, and extracted the data independently. We assessed each trial for risk of bias, and resolved differences by discussion. One RCT, that was an interim report, satisfied the inclusion criteria. We undertook a narrative synthesis of results, as the absence of data and poor reporting precluded us from carrying out any formal statistical analysis. The trial was at high risk of bias. There was not enough evidence available to permit any conclusions to be drawn regarding the use of NPWT for treatment of partial-thickness burn wounds.

Meta-analysis of randomized controlled trials comparing 17α-hydroxyprogesterone caproate and vaginal progesterone for the prevention of recurrent spontaneous preterm delivery.

PubMed

Oler, Elizabeth; Eke, Ahizechukwu C; Hesson, Ashley

2017-07-01

Vaginal progesterone and 17α-hydroxyprogesterone (17α-OHP) are both used to prevent preterm delivery in women who have experienced spontaneous preterm delivery (SPTD) previously. Randomized trial data of the comparative effectiveness of these interventions have been mixed. To compare the efficacy of intramuscular 17α-OHP and vaginal progesterone in the prevention of recurrent SPTD. Cochrane Central Register of Controlled Trials, African Journals Online, Embase, Google Scholar, ISI Web of Science, LILACS, CINAHL, PubMed, and registers of ongoing trials were searched using keywords related to 17α-OHP, vaginal progesterone, and preterm delivery. Randomized controlled trials published between January 1, 1966, and November 30, 2016, comparing 17α-OHP and vaginal progesterone for the prevention of recurrent SPTD during singleton pregnancies were included. Study data were extracted and meta-analyses were performed when outcomes were comparable. The meta-analyses included data from three randomized trials. Lower rates of SPTD before 34 weeks (relative risk 0.71, 95% confidence interval 0.53-0.95) and before 32 weeks (relative risk 0.62, 95% confidence interval 0.40-0.94) of pregnancy were observed among patients treated with vaginal progesterone. Vaginal progesterone and 17α-OHP were comparable for the prevention of recurrent SPTD in singleton pregnancies; vaginal progesterone could be superior. © 2017 International Federation of Gynecology and Obstetrics.

Comparison of an interactive with a didactic educational intervention for improving the evidence-based practice knowledge of occupational therapists in the public health sector in South Africa: a randomised controlled trial.

PubMed

Buchanan, Helen; Siegfried, Nandi; Jelsma, Jennifer; Lombard, Carl

2014-06-10

Despite efforts to identify effective interventions to implement evidence-based practice (EBP), uncertainty remains. Few existing studies involve occupational therapists or resource-constrained contexts. This study aimed to determine whether an interactive educational intervention (IE) was more effective than a didactic educational intervention (DE) in improving EBP knowledge, attitudes and behaviour at 12 weeks. A matched pairs design, randomised controlled trial was conducted in the Western Cape of South Africa. Occupational therapists employed by the Department of Health were randomised using matched-pair stratification by type (clinician or manager) and knowledge score. Allocation to an IE or a DE was by coin-tossing. A self-report questionnaire (measuring objective knowledge and subjective attitudes) and audit checklist (measuring objective behaviour) were completed at baseline and 12 weeks. The primary outcome was EBP knowledge at 12 weeks while secondary outcomes were attitudes and behaviour at 12 weeks. Data collection occurred at participants' places of employment. Audit raters were blinded, but participants and the provider could not be blinded. Twenty-one of 28 pairs reported outcomes, but due to incomplete data for two participants, 19 pairs were included in the analysis. There was a median increase of 1.0 points (95% CI = -4.0, 1.0) in the IE for the primary outcome (knowledge) compared with the DE, but this difference was not significant (P = 0.098). There were no significant differences on any of the attitude subscale scores. The median 12-week audit score was 8.6 points higher in the IE (95% CI = -7.7, 27.0) but this was not significant (P = 0.196). Within-group analyses showed significant increases in knowledge in both groups (IE: T = 4.0, P <0.001; DE: T = 12.0, P = 0.002) but no significant differences in attitudes or behaviour. The results suggest that the interventions had similar outcomes at 12 weeks and that the interactive component had little additional effect. Pan African Controlled Trials Register PACTR201201000346141, registered 31 January 2012. Clinical Trials NCT01512823, registered 1 February 2012. South African National Clinical Trial Register DOH2710093067, registered 27 October 2009. The first participants were randomly assigned on 16 July 2008.

Statistical analysis plan for the Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial (LiGHT): a multi-centre randomised controlled trial.

PubMed

Vickerstaff, Victoria; Ambler, Gareth; Bunce, Catey; Xing, Wen; Gazzard, Gus

2015-11-11

The LiGHT trial (Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial) is a multicentre randomised controlled trial of two treatment pathways for patients who are newly diagnosed with open-angle glaucoma (OAG) and ocular hypertension (OHT). The main hypothesis for the trial is that lowering intraocular pressure (IOP) with selective laser trabeculoplasty (SLT) as the primary treatment ('Laser-1st') leads to a better health-related quality of life than for those started on IOP-lowering drops as their primary treatment ('Medicine-1st') and that this is associated with reduced costs and improved tolerability of treatment. This paper describes the statistical analysis plan for the study. The LiGHT trial is an unmasked, multi-centre randomised controlled trial. A total of 718 patients (359 per arm) are being randomised to two groups: medicine-first or laser-first treatment. Outcomes are recorded at baseline and at 6-month intervals up to 36 months. The primary outcome measure is health-related quality of life (HRQL) at 36 months measured using the EQ-5D-5L. The main secondary outcome is the Glaucoma Utility Index. We plan to analyse the patient outcome data according to the group to which the patient was originally assigned. Methods of statistical analysis are described, including the handling of missing data, the covariates used in the adjusted analyses and the planned sensitivity analyses. The trial was registered with the ISRCTN register on 23/07/2012, number ISRCTN32038223 .

Effectiveness and cost effectiveness of counselling in primary care.

PubMed

Bower, P; Rowland, N; Mellor, C l; Heywood, P; Godfrey, C; Hardy, R

2002-01-01

Counsellors are prevalent in primary care settings. However, there are concerns about the clinical and cost-effectiveness of the treatments they provide, compared with alternatives such as usual care from the general practitioner, medication or other psychological therapies. To assess the effectiveness and cost effectiveness of counselling in primary care by reviewing cost and outcome data in randomised controlled trials, controlled clinical trials and controlled patient preference trials of counselling interventions in primary care, for patients with psychological and psychosocial problems considered suitable for counselling. The original search strategy included electronic searching of databases (including the CCDAN Register of RCTs and CCTs) along with handsearching of a specialist journal. Published and unpublished sources (clinical trials, books, dissertations, agency reports etc.) were searched, and their reference lists scanned to uncover further controlled trials. Contact was made with subject experts and CCDAN members in order to uncover further trials. For the updated review, searches were restricted to those databases judged to be high yield in the first version of the review: MEDLINE, EMBASE, PSYCLIT and CINAHL, the Cochrane Controlled Trials register and the CCDAN trials register. All controlled trials comparing counselling in primary care with other treatments for patients with psychological and psychosocial problems considered suitable for counselling. Trials completed before the end of June 2001 were included in the review. Data were extracted using a standardised data extraction sheet. The relevant data were entered into the Review Manager software. Trials were quality rated, using CCDAN criteria, to assess the extent to which their design and conduct were likely to have prevented systematic error. Continuous measures of outcome were combined using standardised mean differences. An overall effect size was calculated for each outcome with 95% confidence intervals. Continuous data from different measuring instruments were transformed into a standard effect size by dividing mean values by standard deviations. In view of the diversity of counselling services in primary care (the range of treatments, patients and practitioners) tests of heterogeneity were done to assess the feasibility of aggregating measures of outcome from trials. Sensitivity analyses were undertaken to test the robustness of the results. Seven trials were included in the review. The main analyses showed significantly greater clinical effectiveness in the counselling group compared with 'usual care' in the short-term (standardised mean difference -0.28, 95% CI -0.43 to -0.13, n=772, 6 trials) but not the long-term (standardised mean difference -0.09, 95% CI -0.27 to 0.10, n=475, 4 trials). Levels of satisfaction with counselling were high. Four studies reported similar total costs associated with counselling and usual care over the long-term. However, the economic analyses were likely to be underpowered. Counselling is associated with modest improvement in short-term outcome compared to 'usual care', but provides no additional advantages in the long-term. Patients are satisfied with counselling, and it may not be associated with increased costs.

N-acetylcysteine for sepsis and systemic inflammatory response in adults.

PubMed

Szakmany, Tamas; Hauser, Balázs; Radermacher, Peter

2012-09-12

Death is common in systemic inflammatory response syndrome (SIRS) or sepsis-induced multisystem organ failure and it has been thought that antioxidants such as N-acetylcysteine could be beneficial. We assessed the clinical effectiveness of intravenous N-acetylcysteine for the treatment of patients with SIRS or sepsis. We searched the following databases: Cochrane Central Register of Clinical Trials (CENTRAL) (The Cochrane Library 2011, Issue 12); MEDLINE (January 1950 to January 2012); EMBASE (January 1980 to January 2012); CINAHL (1982 to January 2012); the NHS Trusts Clinical Trials Register and Current Controlled Trials (www.controlled-trials.com); LILACS; KoreaMED; MEDCARIB; INDMED; PANTELEIMON; Ingenta; ISI Web of Knowledge and the National Trials Register to identify all relevant randomized controlled trials available for review. We included only randomized controlled trials (RCTs) in the meta-analysis. We independently performed study selection, quality assessment and data extraction. We estimated risk ratios (RR) for dichotomous outcomes. We measured statistical heterogeneity using the I(2) statistic. We included 41 fully published studies (2768 patients). Mortality was similar in the N-acetylcysteine group and the placebo group (RR 1.06, 95% CI 0.79 to 1.42; I(2) = 0%). Neither did N-acetylcysteine show any significant effect on length of stay, duration of mechanical ventilation or incidence of new organ failure. Early application of N-acetylcysteine to prevent the development of an oxidato-inflammatory response did not affect the outcome, nor did late application that is after 24 hours of developing symptoms. Late application was associated with cardiovascular instability. Overall, this meta-analysis puts doubt on the safety and utility of intravenous N-acetylcysteine as an adjuvant therapy in SIRS and sepsis. At best, N-acetylcysteine is ineffective in reducing mortality and complications in this patient population. At worst, it can be harmful, especially when administered later than 24 hours after the onset of symptoms, by causing cardiovascular depression. Unless future RCTs provide evidence of treatment effect, clinicians should not routinely use intravenous N-acetylcysteine in SIRS or sepsis and academics should not promote its use.

The impact of financial incentives on participants' food purchasing patterns in a supermarket-based randomized controlled trial.

PubMed

Olstad, Dana Lee; Crawford, David A; Abbott, Gavin; McNaughton, Sarah A; Le, Ha Nd; Ni Mhurchu, Cliona; Pollard, Christina; Ball, Kylie

2017-08-25

The impacts of supermarket-based nutrition promotion interventions might be overestimated if participants shift their proportionate food purchasing away from their usual stores. This study quantified whether participants who received price discounts on fruits and vegetables (FV) in the Supermarket Healthy Eating for Life (SHELf) randomized controlled trial (RCT) shifted their FV purchasing into study supermarkets during the intervention period. Participants were 642 females randomly assigned to a 1) skill-building (n = 160), 2) price reduction (n = 161), 3) combined skill-building and price reduction (n = 160), or 4) control (n = 161) group. Participants self-reported the proportion of FV purchased in study supermarkets at baseline, 3- and 6-months post-intervention. Fisher's exact and χ 2 tests assessed differences among groups in the proportion of FV purchased in study supermarkets at each time point. Multinomial logistic regression assessed differences among groups in the change in proportionate FV purchasing over time. Post-intervention, 49% of participants purchased ≥50% of their FV in study supermarkets. Compared to all other groups, the price reduction group was approximately twice as likely (RRR: 1.8-2.2) to have increased proportionate purchasing of FV in study supermarkets from baseline to post-intervention (p< 0.05). Participants who received price reductions on FV were approximately twice as likely to shift their FV purchasing from other stores into study supermarkets during the intervention period. Unless food purchasing data are available for all sources, differential changes in purchasing patterns can make it difficult to discern the true impacts of nutrition interventions. The SHELf trial is registered with Current Controlled Trials Registration ISRCTN39432901, Registered 30 June 2010, Retrospectively registered ( http://www.isrctn.com/ISRCTN39432901 ).

A systematic review of randomised control trials of sexual health interventions delivered by mobile technologies.

PubMed

Burns, Kara; Keating, Patrick; Free, Caroline

2016-08-12

Sexually transmitted infections (STIs) pose a serious public health problem globally. The rapid spread of mobile technology creates an opportunity to use innovative methods to reduce the burden of STIs. This systematic review identified recent randomised controlled trials that employed mobile technology to improve sexual health outcomes. The following databases were searched for randomised controlled trials of mobile technology based sexual health interventions with any outcome measures and all patient populations: MEDLINE, EMBASE, PsycINFO, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, NHS Health Technology Assessment Database, and Web of Science (science and social science citation index) (Jan 1999-July 2014). Interventions designed to increase adherence to HIV medication were not included. Two authors independently extracted data on the following elements: interventions, allocation concealment, allocation sequence, blinding, completeness of follow-up, and measures of effect. Trials were assessed for methodological quality using the Cochrane risk of bias tool. We calculated effect estimates using intention to treat analysis. A total of ten randomised trials were identified with nine separate study groups. No trials had a low risk of bias. The trials targeted: 1) promotion of uptake of sexual health services, 2) reduction of risky sexual behaviours and 3) reduction of recall bias in reporting sexual activity. Interventions employed up to five behaviour change techniques. Meta-analysis was not possible due to heterogeneity in trial assessment and reporting. Two trials reported statistically significant improvements in the uptake of sexual health services using SMS reminders compared to controls. One trial increased knowledge. One trial reported promising results in increasing condom use but no trial reported statistically significant increases in condom use. Finally, one trial showed that collection of sexual health information using mobile technology was acceptable. The findings suggest interventions delivered by SMS interventions can increase uptake of sexual health services and STI testing. High quality trials of interventions using standardised objective measures and employing a wider range of behavioural change techniques are needed to assess if interventions delivered by mobile phone can alter safer sex behaviours carried out between couples and reduce STIs.

Endorsement of the CONSORT guidelines, trial registration, and the quality of reporting randomised controlled trials in leading nursing journals: A cross-sectional analysis.

PubMed

Jull, Andrew; Aye, Phyu Sin

2015-06-01

To establish the reporting quality of trials published in leading nursing journals and investigate associations between CONSORT Statement or trial registration endorsment and reporting of design elements. The top 15 nursing journals were searched using Medline for randomised controlled trials published in 2012. Journals were categorised as CONSORT and trial registration promoting based on requirements of submitting authors or the journal's webpage as at January 2014. Data on sequence generation, allocation concealment, follow up, blinding, baseline equivalence and sample size calculation were extracted by one author and independently verified by the second author against source data. Seven journals were CONSORT promoting and three of these journals were also trial registration promoting. 114 citations were identified and 83 were randomised controlled trials. Eighteen trials (21.7%) were registered and those published in trial registration promoting journals were more likely to be registered (RR 2.64 95%CI 1.14-6.09). We assessed 68.7% of trials to be low risk of bias for sequence generation, 20.5% for allocation concealment, 38.6% for blinding, 55.4% for completeness of follow up and 79.5% for baseline equivalence. Trials published in CONSORT promoting journals were more likely to be at low risk of bias for blinding (RR 2.33, 95%CI 1.01-5.34) and completeness of follow up (RR 1.77, 95%CI 1.02-3.10), but journal endorsement of the CONSORT Statement or trial registration otherwise had no significant effect. Trials published in CONSORT and trial registration promoting journals were more likely to have high quality sample size calculations (RR 2.91, 95%CI 1.18-7.19 and RR 1.69, 95%CI 1.08-2.64, respectively). Simple endorsement of the CONSORT Statement and trials registration is insufficient action to encourage improvement of the quality of trial reporting across the most important of trial design elements. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.

PubMed

Hussein, Norita; Weng, Stephen F; Kai, Joe; Kleijnen, Jos; Qureshi, Nadeem

2015-08-12

Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 25 June 2015.Date of latest search of all other sources: 10 December 2014. Any randomised or quasi-randomised control trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease when compared to usual care. We identified 19 papers, describing 13 unique trials which were potentially eligible for inclusion in the review. However, after assessment, no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found. No randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found. As no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis, or Tay-Sachs disease were found for inclusion in this review, the research evidence for current policy recommendations is limited to non-randomised studies.Information from well-designed, adequately powered, randomised trials is desirable in order to make more robust recommendations for practice. However, such trials must also consider the legal, ethical, and cultural barriers to implementation of preconception genetic risk assessment.

Huperzine A for vascular dementia.

PubMed

Hao, Zilong; Liu, Ming; Liu, Zhiqin; Lv, Donghao

2009-04-15

Huperzine A, a form of herbal medicine, has been considered as an alternative treatment for vascular dementia (VaD) in China. To assess the efficacy and safety of Huperzine A in patients with vascular dementia. The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG) was searched on 7 July 2008 using the terms: huperzi* OR ayapin OR scoparon*. The CDCIG Specialized Register contains records from all major health care databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many trials databases and grey literature sources. The review authors searched the following databases in August 2008 using the terms 'Huperzine A', 'Shishanjianjia', 'Haboyin' and 'Shuangyiping': The Chinese Biomedical Database (CBM) (1977 to August 2008); Chinese Science and Technique Journals Database (VIP) (1989 to August 2008); China National Knowledge Infrastructure (CNKI) (1979 to August 2008); The Chinese Clinical Trials Register (ChiCTR, August 2008); Google (August 2008). In addition, the review authors searched reference lists, relevant clinical trials and contacted researchers in an effort to identify further published and unpublished studies. Randomized controlled trials comparing Huperzine A with placebo in patients with vascular dementia were considered eligible for inclusion. Two review authors independently selected trials for inclusion, assessed trial quality, and extracted data. Only one small trial, involving 14 participants, was included. No significant beneficial effect of Huperzine A on the improvement of cognitive function measured by MMSE for VaD (WMD 2.40; 95% CI -4.78 to 9.58) was observed. No death from all causes at the end of treatment were reported. At present, other outcome measures were not available in any of the trials. Although no statistically significant differences were found between the Huperzine A-treated and control groups, the confidence intervals for the treatment effect estimates were wide and included both clinically significant benefits and clinically significant harms. There is no [convincing] evidence that Huperzine A is of value in vascular dementia based on one small trial. It deserves further research.

Exit interviews to reduce turnover amongst healthcare professionals.

PubMed

Flint, Anndrea; Webster, Joan

2013-03-28

Exit interviews are widely used in healthcare organisations to identify reasons for staff attrition, yet their usefulness in limiting turnover is unclear. To determine the effectiveness of various exit interview strategies in decreasing turnover rates amongst healthcare professionals. We searched the Cochrane EPOC Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL), Issue 11, 2012; MEDLINE, Ovid (1950- ); EMBASE, Ovid (1947- ); CINAHL, EbscoHost (1980- ), and PsycINFO, OVID (1806-) between October 31 and November 6, 2012. We also screened the reference lists of included studies and relevant reviews; and searched trial registries for planned and on-going trials. We did not restrict searches by language or publication date. Randomised controlled trials, controlled clinical trials, controlled before-after studies and interrupted time series studies comparing turnover rates between healthcare professionals who had undergone one form of exit interview with another form of exit interview or with no interview. Two review authors independently assessed trial quality and extracted data. The original search identified 1560 citations, of which we considered 19 potentially relevant. The two authors independently reviewed the abstracts of these studies and retrieved the full texts of eight studies. We excluded all eight following independent assessment; they were either interviews, commentaries on how to do an exit interview or descriptive studies about reasons for leaving. We found no trials that matched our inclusion criteria. For this first update, we screened 2220 citations and identified no new trials. Evidence about the effectiveness of exit interviews to reduce turnover is currently not available. However, exit interviews may provide useful information about the work environment which, in turn, may be useful in the development of interventions to reduce turnover.

Exit interviews to reduce turnover amongst healthcare professionals.

PubMed

Webster, Joan; Flint, Anndrea

2014-03-15

Exit interviews are widely used in healthcare organisations to identify reasons for staff attrition, yet their usefulness in limiting turnover is unclear. To determine the effectiveness of various exit interview strategies in decreasing turnover rates amongst healthcare professionals. We searched the Cochrane EPOC Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL), Issue 11, 2012; MEDLINE, Ovid (1950- ); EMBASE, Ovid (1947- ); CINAHL, EbscoHost (1980- ), and PsycINFO, OVID (1806-) between October 31 and November 6, 2012. We also screened the reference lists of included studies and relevant reviews; and searched trial registries for planned and on-going trials. We did not restrict searches by language or publication date. Randomised controlled trials, controlled clinical trials, controlled before-after studies and interrupted time series studies comparing turnover rates between healthcare professionals who had undergone one form of exit interview with another form of exit interview or with no interview. Two review authors independently assessed trial quality and extracted data. The original search identified 1560 citations, of which we considered 19 potentially relevant. The two authors independently reviewed the abstracts of these studies and retrieved the full texts of eight studies. We excluded all eight following independent assessment; they were either interviews, commentaries on how to do an exit interview or descriptive studies about reasons for leaving. We found no trials that matched our inclusion criteria. For this first update, we screened 2220 citations and identified no new trials. Evidence about the effectiveness of exit interviews to reduce turnover is currently not available. However, exit interviews may provide useful information about the work environment which, in turn, may be useful in the development of interventions to reduce turnover.

Physical therapy for Bell s palsy (idiopathic facial paralysis).

PubMed

Teixeira, Lázaro Juliano; Soares, Bernardo Garcia de Oliveira; Vieira, Vanessa Pedrosa; Prado, Gilmar F

2008-07-16

Bell's palsy (idiopathic facial paralysis) is commonly treated by physical therapy services with various therapeutic strategies and devices. There are many questions about their efficacy and effectiveness. To evaluate the efficacy of physical therapies on the outcome of Bell's palsy. We searched the Cochrane Neuromuscular Disease Group Trials Register (February 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2007), MEDLINE (January 1966 to February 2008), EMBASE (January 1980 to February 2008), LILACS (January 1982 to February 2008), PEDro (from 1929 to February 2008), and CINAHL (January 1982 to February 2008). We selected randomised or quasi-randomised controlled trials involving any physical therapy. We included participants of any age with a diagnosis of Bell's palsy and all degrees of severity. The outcome measures were: incomplete recovery six months after randomisation, motor synkinesis, crocodile tears or facial spasm six months after onset, incomplete recovery after one year and adverse effects attributable to the intervention. Titles and abstracts identified from the register were scrutinized. The assessment of methodological quality took into account secure method of randomisation, allocation concealment, observer blinding, patient blinding, differences at baseline of the experimental groups, and completeness of follow-up. Data were extracted using a specially constructed data extraction form. Separate subgroup analyses of participants with more and less severe disability were undertaken. The search identified 45 potentially relevant articles. Six studies met the inclusion criteria. Three trials studied the efficacy of electrostimulation (294 participants) and three exercises (253 participants). Neither treatment produced significantly more improvement than the control treatment or no treatment. There was limited evidence that improvement began earlier in the exercise group. There is no evidence of significant benefit or harm from any physical therapy for idiopathic facial paralysis. The possibility that facial exercise reduces time to recover and sequelae needs confirming with good quality randomised controlled trials.

Recent Clinical Trials in Osteoporosis: A Firm Foundation or Falling Short?

PubMed Central

Lakey, Wanda C.; Batch, Bryan C.; Chiswell, Karen; Tasneem, Asba; Green, Jennifer B.

2016-01-01

The global burden of osteoporotic fractures is associated with significant morbidity, mortality, and healthcare costs. We examined the ClinicalTrials.gov database to determine whether recently registered clinical trials addressed prevention and treatment in those at high risk for fracture. A dataset of 96,346 trials registered in ClinicalTrials.gov was downloaded on September 27, 2010. At the time of the dataset download, 40,970 interventional trials had been registered since October 1, 2007. The osteoporosis subset comprised 239 interventional trials (0.6%). Those trials evaluating orthopedic procedures were excluded. The primary purpose was treatment in 67.0%, prevention in 20.1%, supportive care in 5.8%, diagnostic in 2.2%, basic science in 3.1%, health services research in 0.9%, and screening in 0.9%. The majority of studies (61.1%) included drug-related interventions. Most trials (56.9%) enrolled only women, 38.9% of trials were open to both men and women, and 4.2% enrolled only men. Roughly one fifth (19.7%) of trials excluded research participants older than 65 years, and 33.5% of trials excluded those older than 75 years. The funding sources were industry in 51.0%, the National Institutes of Health in 6.3%, and other in 42.7%. We found that most osteoporosis-related trials registered from October 2007 through September 2010 examined the efficacy and safety of drug treatment, and fewer trials examined prevention and non-drug interventions. Trials of interventions that are not required to be registered in ClinicalTrials.gov may be underrepresented. Few trials are specifically studying osteoporosis in men and older adults. Recently registered osteoporosis trials may not sufficiently address fracture prevention. PMID:27191848

Antibiotic prophylaxis for term or near-term premature rupture of membranes: metaanalysis of randomized trials.

PubMed

Saccone, Gabriele; Berghella, Vincenzo

2015-05-01

The objective of the study was to evaluate the efficacy of antibiotic prophylaxis in women with term or near-term premature rupture of membranes. Searches were performed in MEDLINE, OVID, Scopus, ClinicalTrials.gov, the PROSPERO International Prospective Register of Systematic Reviews, EMBASE, ScienceDirect.com, MEDSCAPE, and the Cochrane Central Register of Controlled Trials with the use of a combination of key words and text words related to antibiotics, premature rupture of membranes, term, and trials from inception of each database to September 2014. We included all randomized trials of singleton gestations with premature rupture of membranes at 36 weeks or more, who were randomized to antibiotic prophylaxis or control (either placebo or no treatment). The primary outcomes included maternal chorioamnionitis and neonatal sepsis. A subgroup analysis on studies with latency more than 12 hours was planned. Before data extraction, the review was registered with the PROSPERO International Prospective Register of Systematic Reviews (registration number CRD42014013928). The metaanalysis was performed following the Preferred Reporting Item for Systematic Reviews and Meta-analyses statement. Women who received antibiotics had the same rate of chorioamnionitis (2.7% vs 3.7%; relative risk [RR], 0.73, 95% confidence interval [CI], 0.48-1.12), endometritis (0.4% vs 0.9%; RR, 0.44, 95% CI, 0.18-1.10), maternal infection (3.1% vs 4.6%; RR, 0.48, 95% CI, 0.19-1.21), and neonatal sepsis (1.0% vs 1.4%; RR, 0.69, 95% CI, 0.34-1.39). In the planned subgroup analysis, women with latency longer than 12 hours, who received antibiotics, had a lower rate of chorioamnionitis (2.9% vs 6.1%; RR, 0.49, 95% CI, 0.27-0.91) and endometritis (0% vs 2.2%; RR, 0.12, 95% CI, 0.02-0.62) compared with the control group. Antibiotic prophylaxis for term or near-term premature rupture of membranes is not associated with any benefits in either maternal or neonatal outcomes. In women with latency longer than 12 hours, prophylactic antibiotics are associated with significantly lower rates of chorioamnionitis by 51% and endometritis by 88%. Copyright © 2015 Elsevier Inc. All rights reserved.

Price discounts significantly enhance fruit and vegetable purchases when combined with nutrition education: a randomized controlled supermarket trial.

PubMed

Waterlander, Wilma E; de Boer, Michiel R; Schuit, Albertine J; Seidell, Jacob C; Steenhuis, Ingrid H M

2013-04-01

Reducing fruit and vegetable (F&V) prices is a frequently considered policy to improve dietary habits in the context of health promotion. However, evidence on the effectiveness of this intervention is limited. The objective was to examine the effects of a 50% price discount on F&Vs or nutrition education or a combination of both on supermarket purchases. A 6-mo randomized controlled trial within Dutch supermarkets was conducted. Regular supermarket shoppers were randomly assigned to 1 of 4 conditions: 50% price discounts on F&Vs, nutrition education, 50% price discounts plus nutrition education, or no intervention. A total of 199 participants provided baseline data; 151 (76%) were included in the final analysis. F&V purchases were measured by using supermarket register receipts at baseline, at 1 mo after the start of the intervention, at 3 mo, at 6 mo (end of the intervention period), and 3 mo after the intervention ended (9 mo). Adjusted multilevel models showed significantly higher F&V purchases (per household/2 wk) as a result of the price discount (+3.9 kg; 95% CI: 1.5, 6.3 kg) and the discount plus education intervention (+5.6 kg; 95% CI: 3.2, 7.9 kg) at 6 mo compared with control. Moreover, the percentage of participants who consumed recommended amounts of F&Vs (≥400 g/d) increased from 42.5% at baseline to 61.3% at 6 mo in both discount groups (P = 0.03). Education alone had no significant effect. Discounting F&Vs is a promising intervention strategy because it resulted in substantially higher F&V purchases, and no adverse effects were observed. Therefore, pricing strategies form an important focus for future interventions or policy. However, the long-term effects and the ultimate health outcomes require further investigation. This trial was registered at the ISRCTN Trial Register as number ISRCTN56596945 and at the Dutch Trial Register (http://www.trialregister.nl/trialreg/index.asp) as number NL22568.029.08.

Physiotherapy treatment approaches for the recovery of postural control and lower limb function following stroke: a systematic review.

PubMed

Pollock, Alex; Baer, Gillian; Langhorne, Peter; Pomeroy, Valerie

2007-05-01

To determine whether there is a difference in global dependency and functional independence in patients with stroke associated with different approaches to physiotherapy treatment. We searched the Cochrane Stroke Group Trials Register (last searched May 2005), Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 2, 2005), MEDLINE (1966 to May 2005), EMBASE (1980 to May 2005) and CINAHL (1982 to May 2005). We contacted experts and researchers with an interest in stroke rehabilitation. Inclusion criteria were: (a) randomized or quasi-randomized controlled trials; (b) adults with a clinical diagnosis of stroke; (c) physiotherapy treatment approaches aimed at promoting postural control and lower limb function; (d) measures of disability, motor impairment or participation. Two independent reviewers categorized identified trials according to the inclusion/exclusion criteria, documented the methodological quality and extracted the data. Twenty trials (1087 patients) were included in the review. Comparisons included: neurophysiological approach versus other approach; motor learning approach versus other approach; mixed approach versus other approach for the outcomes of global dependency and functional independence. A mixed approach was significantly more effective than no treatment control at improving functional independence (standardized mean difference (SMD) 0.94, 95% confidence interval (CI) 0.08 to 1.80). There were no significant differences found for any other comparisons. Physiotherapy intervention, using a 'mix' of components from different 'approaches' is more effective than no treatment control in attaining functional independence following stroke. There is insufficient evidence to conclude that any one physiotherapy 'approach' is more effective in promoting recovery of disability than any other approach.

Therapeutic touch for healing acute wounds.

PubMed

O'Mathúna, Dónal P; Ashford, Robert L

2014-07-29

Therapeutic Touch (TT) is an alternative therapy that has gained popularity over the past two decades for helping wounds to heal. Practitioners enter a meditative state and pass their hands above the patient's body to find and correct any imbalances in the patient's 'life energy' or chi. Scientific instruments have been unable to detect this energy. The effect of TT on wound healing has been expounded in anecdotal publications. To identify and review all relevant data to determine the effects of TT on healing acute wounds. In January 2014, for this fifth update, we searched The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. All randomised or quasi-randomised controlled trials, which compared the effect of TT with a placebo, another treatment, or no treatment control were considered. Studies which used TT as a stand-alone treatment, or as an adjunct to other therapies, were eligible. One author (DO'M) determined the eligibility for inclusion of all trials in the review. Both authors conducted data extraction and evaluation of trial validity independently. Each trial was assessed using predetermined criteria. No new trials were identified for this update. Four trials in people with experimental wounds were included. The effect of TT on wound healing in these studies was variable. Two trials (n = 44 & 24) demonstrated a significant increase in healing associated with TT, while one trial found significantly worse healing after TT and the other found no significant difference. All trials are at high risk of bias. There is no robust evidence that TT promotes healing of acute wounds.

Therapeutic touch for healing acute wounds.

PubMed

O'Mathúna, Dónal P

2016-08-23

Therapeutic Touch (TT) is an alternative therapy that has gained popularity over the past two decades for helping wounds to heal. Practitioners enter a meditative state and pass their hands above the patient's body to find and correct any imbalances in the patient's 'life energy' or chi. Scientific instruments have been unable to detect this energy. The effect of TT on wound healing has been expounded in anecdotal publications. To identify and review all relevant data to determine the effects of TT on healing acute wounds. In January 2014, for this fifth update, we searched The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. All randomised or quasi-randomised controlled trials, which compared the effect of TT with a placebo, another treatment, or no treatment control were considered. Studies which used TT as a stand-alone treatment, or as an adjunct to other therapies, were eligible. One author (DO'M) determined the eligibility for inclusion of all trials in the review. Both authors conducted data extraction and evaluation of trial validity independently. Each trial was assessed using predetermined criteria. No new trials were identified for this update. Four trials in people with experimental wounds were included. The effect of TT on wound healing in these studies was variable. Two trials (n = 44 & 24) demonstrated a significant increase in healing associated with TT, while one trial found significantly worse healing after TT and the other found no significant difference. All trials are at high risk of bias. There is no robust evidence that TT promotes healing of acute wounds.

Therapeutic touch for healing acute wounds.

PubMed

O'Mathúna, Dónal P; Ashford, Robert L

2012-06-13

Therapeutic Touch (TT) is an alternative therapy that has gained popularity over the past two decades for helping wounds to heal. Practitioners enter a meditative state and pass their hands above the patient's body to find and correct any imbalances in the patient's 'life energy' or chi. Scientific instruments have been unable to detect this energy. The effect of TT on wound healing has been expounded in anecdotal publications. To identify and review all relevant data to determine the effects of TT on healing acute wounds. For this fourth update, we searched The Cochrane Wounds Group Specialised Register (searched 27 January 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1); Ovid MEDLINE (2010 to January Week 2 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, January 26, 2012); Ovid EMBASE (2010 to 2012 Week 03); and EBSCO CINAHL (2010 to January 6 2012). All randomised or quasi-randomised controlled trials, which compared the effect of TT with a placebo, another treatment, or no treatment control were considered. Studies which used TT as a stand-alone treatment, or as an adjunct to other therapies, were eligible. One author (DO'M) determined the eligibility for inclusion of all trials in the review. Both authors conducted data extraction and evaluation of trial validity independently. Each trial was assessed using predetermined criteria. No new trials were identified for this update. Four trials in people with experimental wounds were included. The effect of TT on wound healing in these studies was variable. Two trials (n = 44 & 24) demonstrated a significant increase in healing associated with TT, while one trial found significantly worse healing after TT and the other found no significant difference. All trials are at high risk of bias. There is no robust evidence that TT promotes healing of acute wounds.

Therapeutic touch for healing acute wounds.

PubMed

O'Mathúna, Dónal P

2016-05-03

Therapeutic Touch (TT) is an alternative therapy that has gained popularity over the past two decades for helping wounds to heal. Practitioners enter a meditative state and pass their hands above the patient's body to find and correct any imbalances in the patient's 'life energy' or chi. Scientific instruments have been unable to detect this energy. The effect of TT on wound healing has been expounded in anecdotal publications. To identify and review all relevant data to determine the effects of TT on healing acute wounds. In January 2014, for this fifth update, we searched The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. All randomised or quasi-randomised controlled trials, which compared the effect of TT with a placebo, another treatment, or no treatment control were considered. Studies which used TT as a stand-alone treatment, or as an adjunct to other therapies, were eligible. One author (DO'M) determined the eligibility for inclusion of all trials in the review. Both authors conducted data extraction and evaluation of trial validity independently. Each trial was assessed using predetermined criteria. No new trials were identified for this update. Four trials in people with experimental wounds were included. The effect of TT on wound healing in these studies was variable. Two trials (n = 44 & 24) demonstrated a significant increase in healing associated with TT, while one trial found significantly worse healing after TT and the other found no significant difference. All trials are at high risk of bias. There is no robust evidence that TT promotes healing of acute wounds.

Occupational therapy for patients with problems in personal activities of daily living after stroke: systematic review of randomised trials

PubMed Central

Drummond, Avril; Leonardi-Bee, Jo; Gladman, J R F; Donkervoort, Mireille; Edmans, Judi; Gilbertson, Louise; Jongbloed, Lyn; Logan, Pip; Sackley, Catherine; Walker, Marion; Langhorne, Peter

2007-01-01

Objective To determine whether occupational therapy focused specifically on personal activities of daily living improves recovery for patients after stroke. Design Systematic review and meta-analysis. Data sources The Cochrane stroke group trials register, the Cochrane central register of controlled trials, Medline, Embase, CINAHL, PsycLIT, AMED, Wilson Social Sciences Abstracts, Science Citation Index, Social Science Citation, Arts and Humanities Citation Index, Dissertations Abstracts register, Occupational Therapy Research Index, scanning reference lists, personal communication with authors, and hand searching. Review methods Trials were included if they evaluated the effect of occupational therapy focused on practice of personal activities of daily living or where performance in such activities was the target of the occupational therapy intervention in a stroke population. Original data were sought from trialists. Two reviewers independently reviewed each trial for methodological quality. Disagreements were resolved by consensus. Results Nine randomised controlled trials including 1258 participants met the inclusion criteria. Occupational therapy delivered to patients after stroke and targeted towards personal activities of daily living increased performance scores (standardised mean difference 0.18, 95% confidence interval 0.04 to 0.32, P=0.01) and reduced the risk of poor outcome (death, deterioration or dependency in personal activities of daily living) (odds ratio 0.67, 95% confidence interval 0.51 to 0.87, P=0.003). For every 100 people who received occupational therapy focused on personal activities of daily living, 11 (95% confidence interval 7 to 30) would be spared a poor outcome. Conclusions Occupational therapy focused on improving personal activities of daily living after stroke can improve performance and reduce the risk of deterioration in these abilities. Focused occupational therapy should be available to everyone who has had a stroke. PMID:17901469

The acute and sub-chronic effects of cocoa flavanols on mood, cognitive and cardiovascular health in young healthy adults: a randomized, controlled trial.

PubMed

Massee, Laura A; Ried, Karin; Pase, Matthew; Travica, Nikolaj; Yoganathan, Jaesshanth; Scholey, Andrew; Macpherson, Helen; Kennedy, Greg; Sali, Avni; Pipingas, Andrew

2015-01-01

Cocoa supplementation has been associated with benefits to cardiovascular health. However, cocoa's effects on cognition are less clear. A randomized, placebo-controlled, double-blind clinical trial (n = 40, age M = 24.13 years, SD = 4.47 years) was conducted to investigate the effects of both acute (same-day) and sub-chronic (daily for four-weeks) 250 mg cocoa supplementation on mood and mental fatigue, cognitive performance and cardiovascular functioning in young, healthy adults. Assessment involved repeated 10-min cycles of the Cognitive Demand Battery (CDB) encompassing two serial subtraction tasks (Serial Threes and Sevens), a Rapid Visual Information Processing task, and a mental fatigue scale over the course of half an hour. The Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) was also completed to evaluate cognition. Cardiovascular function included measuring both peripheral and central blood pressure and cerebral blood flow. At the acute time point, consumption of cocoa significantly improved self-reported mental fatigue and performance on the Serial Sevens task in cycle one of the CDB. No other significant effects were found. This trial was registered with the Australian and New Zealand Clinical Trial Registry (Trial ID: ACTRN12613000626763). Accessible via http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12613000626763&ddlSearch=Registered.

Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials.

PubMed

Roth, Daniel E; Leung, Michael; Mesfin, Elnathan; Qamar, Huma; Watterworth, Jessica; Papp, Eszter

2017-11-29

Objectives  To estimate the effects of vitamin D supplementation during pregnancy on 11 maternal and 27 neonatal/infant outcomes; to determine frequencies at which trial outcome data were missing, unreported, or inconsistently reported; and to project the potential contributions of registered ongoing or planned trials. Design  Systematic review and meta-analysis of randomised controlled trials; systematic review of registered but unpublished trials. Data sources  Medline, Embase, PubMed, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception to September 2017; manual searches of reference lists of systematic reviews identified in the electronic search; and online trial registries for unpublished, ongoing, or planned trials. Eligibility criteria for study selection  Trials of prenatal vitamin D supplementation with randomised allocation and control groups administered placebo, no vitamin D, or vitamin D ≤600 IU/day (or its equivalent), and published in a peer reviewed journal. Results  43 trials (8406 participants) were eligible for meta-analyses. Median sample size was 133 participants. Vitamin D increased maternal/cord serum concentration of 25-hydroxyvitamin D, but the dose-response effect was weak. Maternal clinical outcomes were rarely ascertained or reported, but available data did not provide evidence of benefits. Overall, vitamin D increased mean birth weight of 58.33 g (95% confidence interval 18.88 g to 97.78 g; 37 comparisons) and reduced the risk of small for gestational age births (risk ratio 0.60, 95% confidence interval 0.40 to 0.90; seven comparisons), but findings were not robust in sensitivity and subgroup analyses. There was no effect on preterm birth (1.0, 0.77 to 1.30; 15 comparisons). There was strong evidence that prenatal vitamin D reduced the risk of offspring wheeze by age 3 years (0.81, 0.67 to 0.98; two comparisons). For most outcomes, meta-analyses included data from a minority of trials. Only eight of 43 trials (19%) had an overall low risk of bias. Thirty five planned/ongoing randomised controlled trials could contribute 12 530 additional participants to future reviews. Conclusions  Most trials on prenatal vitamin D published by September 2017 were small and of low quality. The evidence to date seems insufficient to guide clinical or policy recommendations. Future trials should be designed and powered to examine clinical endpoints, including maternal conditions related to pregnancy (such as pre-eclampsia), infant growth, and respiratory outcomes. Systematic review registration  PROSPERO CRD42016051292. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Anticonvulsants for preventing seizures in patients with chronic subdural haematoma.

PubMed

Ratilal, Bernardo O; Pappamikail, Lia; Costa, João; Sampaio, Cristina

2013-06-06

Anticonvulsant therapy is sometimes used prophylactically in patients with chronic subdural haematoma, although the benefit is unclear. To assess the effects of prophylactic anticonvulsants in patients with chronic subdural haematoma, in both the pre- and post-operative periods. We searched the Cochrane Injuries Group's Specialised Register, CENTRAL (The Cochrane Library), MEDLINE (OvidSP), EMBASE (OvidSP), PubMed, LILACS, and the databases clinicaltrials.gov, the WHO International Clinical Trials Registry Platform, and Current Controlled Trials. The search was through 27th March 2013. Randomised controlled trials comparing any anticonvulsant versus placebo or no intervention. Three authors screened the search results to identify relevant studies. No studies met the inclusion criteria for the review. No randomised controlled trials were identified. No formal recommendations can be made about the use of prophylactic anticonvulsants in patients with chronic subdural haematoma based on the literature currently available. There are no randomised controlled trials on this topic, and non-controlled studies have conflicting results. There is an urgent need for well-designed randomised controlled trials.

Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection.

PubMed

Henriquez-Camacho, Cesar; Gotuzzo, Eduardo; Echevarria, Juan; White, A Clinton; Terashima, Angelica; Samalvides, Frine; Pérez-Molina, José A; Plana, Maria N

2016-01-18

Strongyloidiasis is a gut infection with Strongyloides stercoralis which is common world wide. Chronic infection usually causes a skin rash, vomiting, diarrhoea or constipation, and respiratory problems, and it can be fatal in people with immune deficiency. It may be treated with ivermectin or albendazole or thiabendazole. To assess the effects of ivermectin versus benzimidazoles (albendazole and thiabendazole) for treating chronic strongyloides infection. We searched the Cochrane Infectious Diseases Group Specialized Register (24 August 2015); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (January 1966 to August 2015); EMBASE (January 1980 to August 2015); LILACS (August 2015); and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) using 'strongyloid*' as a search term, reference lists, and conference abstracts. Randomized controlled trials of ivermectin versus albendazole or thiabendazole for treating chronic strongyloides infection. Two review authors independently extracted data and assessed risk of bias in the included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) and fixed- or random-effects models. We pooled adverse event data if the trials were sufficiently similar in their adverse event definitions. We included seven trials, enrolling 1147 participants, conducted between 1994 and 2011 in different locations (Africa, Southeast Asia, America and Europe).In trials comparing ivermectin with albendazole, parasitological cure was higher with ivermectin (RR 1.79, 95% CI 1.55 to 2.08; 478 participants, four trials, moderate quality evidence). There were no statistically significant differences in adverse events (RR 0.80, 95% CI 0.59 to 1.09; 518 participants, four trials, low quality evidence).In trials comparing ivermectin with thiabendazole, there was little or no difference in parasitological cure (RR 1.07, 95% CI 0.96 to 1.20; 467 participants, three trials, low quality evidence). However, adverse events were less common with ivermectin (RR 0.31, 95% CI 0.20 to 0.50; 507 participants; three trials, moderate quality evidence).In trials comparing different dosages of ivermectin, taking a second dose of 200 μg/kg of ivermectin was not associated with higher cure in a small subgroup of participants (RR 1.02, 95% CI 0.94 to 1.11; 94 participants, two trials).Dizziness, nausea, and disorientation were commonly reported in all drug groups. There were no reports of serious adverse events or death. Ivermectin results in more people cured than albendazole, and is at least as well tolerated. In trials of ivermectin with thiabendazole, parasitological cure is similar but there are more adverse events with thiabendazole.

Tight control of mild-moderate pre-existing or non-proteinuric gestational hypertension.

PubMed

Nabhan, Ashraf F; Elsedawy, Maged M

2011-07-06

The question of the target blood pressure in pregnant women with mild-moderate hypertension continues to be an area of debate. To compare tight versus very tight control of mild-moderate pre-existing or non-proteinuric gestational hypertension for improving outcomes We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2011), CENTRAL (The Cochrane Library 2011, Issue 3), MEDLINE (January 1966 to March 2011), and the metaRegister of Controlled Trials (31 March 2011). We handsearched citation lists of relevant publications, review articles, and included studies. Randomized controlled trials of tight versus very tight control in pregnant women with mild or moderate pre-existing or non-proteinuric gestational hypertension. Two authors independently assessed trial quality and extracted data. We expressed results as risk ratio (RR) or mean differences, together with their 95% confidence intervals (CI). We included two studies (256 participants) with mild-moderate pre-existing or non-proteinuric gestational hypertension. There was no evidence of a difference between tight and very tight control groups regarding severe pre-eclampsia (risk ratio (RR) 1.28, 95% CI 0.97 to 1.70; two trials, 256 participants). More women in the tight group were hospitalized during their pregnancy (RR 2.53, 95% CI 1.14 to 5.63; one trial, 125 participants). There was no evidence of a difference in other outcome measures including fetal distress, IUGR, neonatal admission to a NICU, perinatal deaths, induction of labor and cesarean delivery between the tight and the very tight control groups. Gestational age at delivery had a non-significant mean difference (MD) of -0.15 weeks between the tight and very tight control groups (MD -0.15, 95% CI -1.52 to 1.21, random-effects, T² = 0.75, I² = 77%; two trials, 256 participants). The MD in birthweight between the tight and the very tight control group was not significant (MD -100.00 grams, 95% CI -363.69 to 163.69; one trial, 125 participants). For pregnant women with non-severe pre-existing or non-proteinuric gestational hypertension, there is insufficient evidence to determine how tight control of hypertension should be achieved to improve maternal and fetal-neonatal outcomes.

Characteristics of clinical trials registered in ClinicalTrials.gov, 2007-2010.

PubMed

Califf, Robert M; Zarin, Deborah A; Kramer, Judith M; Sherman, Rachel E; Aberle, Laura H; Tasneem, Asba

2012-05-02

Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials portfolio. To examine fundamental characteristics of interventional clinical trials registered in the ClinicalTrials.gov database. A data set comprising 96,346 clinical studies from ClinicalTrials.gov was downloaded on September 27, 2010, and entered into a relational database to analyze aggregate data. Interventional trials were identified and analyses were focused on 3 clinical specialties-cardiovascular, mental health, and oncology-that together encompass the largest number of disability-adjusted life-years lost in the United States. Characteristics of registered clinical trials as reported data elements in the trial registry; how those characteristics have changed over time; differences in characteristics as a function of clinical specialty; and factors associated with use of randomization, blinding, and data monitoring committees (DMCs). The number of registered interventional clinical trials increased from 28,881 (October 2004-September 2007) to 40,970 (October 2007-September 2010), and the number of missing data elements has generally declined. Most interventional trials registered between 2007 and 2010 were small, with 62% enrolling 100 or fewer participants. Many clinical trials were single-center (66%; 24,788/37,520) and funded by organizations other than industry or the National Institutes of Health (NIH) (47%; 17,592/37,520). Heterogeneity in the reported methods by clinical specialty; sponsor type; and the reported use of DMCs, randomization, and blinding was evident. For example, reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials (adjusted odds ratio [OR], 0.11; 95% CI, 0.09-0.14), earlier-phase vs phase 3 trials (adjusted OR, 0.83; 95% CI, 0.76-0.91), and mental health trials vs those in the other 2 specialties. In similar comparisons, randomization and blinding were less frequently reported in earlier-phase, oncology, and device trials. Clinical trials registered in ClinicalTrials.gov are dominated by small trials and contain significant heterogeneity in methodological approaches, including reported use of randomization, blinding, and DMCs.

Hemispheric resource limitations in comprehending ambiguous pictures.

PubMed

White, H; Minor, S W

1990-03-01

Ambiguous pictures (Roschach inkblots) were lateralized for 100 msec vs. 200 msec to the right and left hemispheres (RH and LH) of 32 normal right-handed males who determined which of two previously presented words (an accurate or inaccurate one) better described the inkblot. Over the first 32 trials, subjects receiving each stimulus exposure duration were less accurate when the hemisphere receiving the stimulus also controlled the hand used to register a keypress response (RH-left hand and LH-right hand trials) than when hemispheric resources were shared, i.e., when one hemisphere controlled stimulus processing and the other controlled response programming. These differences were eliminated when the 32 trials were repeated.

Piracetam for acute ischaemic stroke.

PubMed

Ricci, Stefano; Celani, Maria Grazia; Cantisani, Teresa Anna; Righetti, Enrico

2012-09-12

Piracetam has neuroprotective and antithrombotic effects that may help to reduce death and disability in people with acute stroke. This is an update of a Cochrane Review first published in 1999, and previously updated in 2006 and 2009. To assess the effects of piracetam in acute, presumed ischaemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched 15 May 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (1966 to May 2011), EMBASE (1980 to May 2011), and ISI Science Citation Index (1981 to May 2011). We also contacted the manufacturer of piracetam to identify further published and unpublished studies. Randomised trials comparing piracetam with control, with at least mortality reported and entry to the trial within three days of stroke onset. Two review authors extracted data and assessed trial quality and this was checked by the other two review authors. We contacted study authors for missing information. We included three trials involving 1002 patients, with one trial contributing 93% of the data. Participants' ages ranged from 40 to 85 years, and both sexes were equally represented. Piracetam was associated with a statistically non-significant increase in death at one month (approximately 31% increase, 95% confidence interval 81% increase to 5% reduction). This trend was no longer apparent in the large trial after correction for imbalance in stroke severity. Limited data showed no difference between the treatment and control groups for functional outcome, dependence or proportion of patients dead or dependent. Adverse effects were not reported. There is some suggestion (but no statistically significant result) of an unfavourable effect of piracetam on early death, but this may have been caused by baseline differences in stroke severity in the trials. There is not enough evidence to assess the effect of piracetam on dependence.

Propofol versus thiopental sodium for the treatment of refractory status epilepticus.

PubMed

Prabhakar, Hemanshu; Bindra, Ashish; Singh, Gyaninder Pal; Kalaivani, Mani

2012-08-15

Failure to respond to antiepileptic drugs in uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (10 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library 2012), and MEDLINE (1946 to May week 1, 2012). We also searched (10 May 2012) ClinicalTrials.gov, The South Asian Database of Controlled Clinical Trials, and IndMED (a bibliographic database of Indian Medical Journals). All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol. Two review authors screened the search results and reviewed abstracts of relevant and eligible trials before retrieving the full text publications. One study was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE and receiving either propofol or thiopental sodium for the control of seizure activity (Rossetti 2011). This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. There was no evidence of a difference between the drugs with respect to the outcome measures such as control of seizure activity and functional outcome at three months. There is lack of robust and randomised controlled evidence that can clarify the efficacy of propofol and thiopental sodium over each other in the treatment of RSE. There is a need for large, randomised controlled trials for this serious condition.

Vitamin C as an adjuvant for treating major depressive disorder and suicidal behavior, a randomized placebo-controlled clinical trial.

PubMed

Sahraian, Ali; Ghanizadeh, Ahmad; Kazemeini, Fereshteh

2015-03-14

There are some animal studies suggesting the possible role of vitamin C for treating depression. However, the efficacy of vitamin C for treating adult patients with major depressive disorder (MDD) has never been examined. This 8-week randomized double-blind placebo-controlled clinical trial included adult patients with major depressive disorder according to DSM-IV diagnostic criteria. Twenty-one patients in the treatment group received citalopram plus vitamin C and the 22 patients in the control group received citalopram plus placebo. The Hamilton Depression Rating Scale was used to measure depressive symptoms at baseline, week 2, week 4, and week 8. We also checked for the presence of adverse effects. While depression symptoms decreased in both groups during this trial, there was no statistically significant difference between the 2 groups (P = .5). The rate of remission, partial response, and complete response was not different between the two groups. The rate of adverse effects were not different between the two groups. Adding vitamin C to citalopram did not increase the efficacy of citalopram in MDD patients. Vitamin C plus citalopram is as effective as placebo plus citalopram for treating adult patients with suicidal behavior. No serious adverse effect for this combination was identified during this trial. This trial was registered at http://www.irct.ir . The registration number of this trial was: IRCT201312263930N31 . Date registered: 5 July 2014.

Gait training assisted by multi-channel functional electrical stimulation early after stroke: study protocol for a randomized controlled trial.

PubMed

van Bloemendaal, Maijke; Bus, Sicco A; de Boer, Charlotte E; Nollet, Frans; Geurts, Alexander C H; Beelen, Anita

2016-10-01

Many stroke survivors suffer from paresis of lower limb muscles, resulting in compensatory gait patterns characterised by asymmetries in spatial and temporal parameters and reduced walking capacity. Functional electrical stimulation has been used to improve walking capacity, but evidence is mostly limited to the orthotic effects of peroneal functional electrical stimulation in the chronic phase after stroke. The aim of this study is to investigate the therapeutic effects of up to 10 weeks of multi-channel functional electrical stimulation (MFES)-assisted gait training on the restoration of spatiotemporal gait symmetry and walking capacity in subacute stroke patients. In a proof-of-principle study with a randomised controlled design, 40 adult patients with walking deficits who are admitted for inpatient rehabilitation within 31 days since the onset of stroke are randomised to either MFES-assisted gait training or conventional gait training. Gait training is delivered in 30-minute sessions each workday for up to 10 weeks. The step length symmetry ratio is the primary outcome. Blinded assessors conduct outcome assessments at baseline, every 2 weeks during the intervention period, immediately post intervention and at 3-month follow-up. This study aims to provide preliminary evidence for the feasibility and effectiveness of MFES-assisted gait rehabilitation early after stroke. Results will inform the design of a larger multi-centre trial. This trial is registered at the Netherlands Trial Register (number NTR4762 , registered 28 August 2014).

Cochrane review: virtual reality for stroke rehabilitation.

PubMed

Laver, K; George, S; Thomas, S; Deutsch, J E; Crotty, M

2012-09-01

Virtual reality and interactive video gaming are innovative therapy approaches in the field of stroke rehabilitation. The primary objective of this review was to determine the effectiveness of virtual reality on motor function after stroke. The impact on secondary outcomes including activities of daily living was also assessed. Randomised and quasi-randomised controlled trials that compared virtual reality with an alternative or no intervention were included in the review. The authors searched the Cochrane Stroke Group Trials Register, the Cochrane Central Register of Controlled Trials, electronic databases, trial registers, reference lists, Dissertation Abstracts, conference proceedings and contacted key researchers and virtual reality manufacturers. Search results were independently examined by two review authors to identify studies meeting the inclusion criteria. Nineteen studies with a total of 565 participants were included in the review. Variation in intervention approaches and outcome data collected limited the extent to which studies could be compared. Virtual reality was found to be significantly more effective than conventional therapy in improving upper limb function (standardised mean difference, SMD) 0.53, 95% confidence intervals [CI] 0.25 to 0.81)) based on seven studies, and activities of daily living (ADL) function (SMD 0.81, 95% CI 0.39 to 1.22) based on three studies. No statistically significant effects were found for grip strength (based on two studies) or gait speed (based on three studies). Virtual reality appears to be a promising approach however, further studies are required to confirm these findings.

Changes to registration elements and results in a cohort of Clinicaltrials.gov trials were not reflected in published articles.

PubMed

Pranić, Shelly; Marušić, Ana

2016-02-01

To assess effectiveness of legislative initiatives to stimulate public registration of trial results, we assessed adherence to protocol and results reporting, changes to registry, and publication data for randomized controlled trials (RCTs) after introduction of Food and Drug Administration Amendment Act (FDAAA). Observational study of a cohort of ClinicalTrials.gov registered FDAAA-covered RCTs found through ClinicalTrials.gov between 2009 and 2012 and data from corresponding publications. WHO Minimum Data Set items were abstracted by one author and verified by the other author. Among 81 eligible trials, most were industry-funded, with a drug intervention in parallel assignment. Secondary outcomes at the initial and last registration were omitted for 17% and 19.7% of RCTs, respectively. RCT registration changes mostly involved scientific title (18.8%). Inclusion criteria omission was most common (88%) in publications. Inferential statistical methods for primary and secondary outcomes matched between registry and publication for 53.4% and 28.6% of RCTs, respectively. Serious and other adverse events (AEs) that were absent for 23.8% and 4.8% of RCTs, respectively, were published as nonoccurring. Discrepancies remain relatively high between registered and published outcomes, particularly regarding registered omissions in publications and concomitant reporting, nature of statistical method used, and reporting of AEs. This seriously undermines transparency of clinical trials and needs immediate attention of all stakeholders in health research. Copyright © 2016 Elsevier Inc. All rights reserved.

Psychological and educational interventions for atopic eczema in children.

PubMed

Ersser, S J; Latter, S; Sibley, A; Satherley, P A; Welbourne, S

2007-07-18

Psychological and educational interventions have been used as an adjunct to conventional therapy for children with atopic eczema to enhance the effectiveness of topical therapy. There have been no relevant systematic reviews applicable to children. To assess the effectiveness of psychological and educational interventions in changing outcomes for children with atopic eczema. We searched the Cochrane Skin Group Specialised Register (to September 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2005), MEDLINE (from 1966-2005), EMBASE (from 1980 to week 3, 2005 ), PsycINFO (from 1872 to week 1, 2005). On-line: National Research Register, Meta-register of Controlled Trials, ZETOC alerts, SIGLE (August 2005). RCTs of psychological or educational interventions, or both, used to manage children with atopic eczema. Two authors independently applied eligibility criteria, assessed trial quality and extracted data. A lack of comparable data prevented data synthesis. Five RCTs met the inclusion criteria. Some included studies required clearer reporting of trial procedures. Rigorous established outcome measures were not always used. Interventions described in all 5 RCTs were adjuncts to conventional therapy. Four focused on intervention directed towards the parents; data synthesis was not possible. Psychological interventions remain virtually unevaluated by studies of robust design; the only included study examined the effect of relaxation techniques (hypnotherapy and biofeedback) on severity. Three educational studies identified significant improvements in disease severity between intervention groups. A recent German trial evaluated long term outcomes and found significant improvements in both disease severity (3 months to 7 years, p=0.0002, 8 to 12 years, p=0.003, 13 to 18 years, p=0.0001) and parental quality of life (3 months to 7 years, p=0.0001, 8 to 12 years p=0.002), for children with atopic eczema. One study found video-based education more effective in improving severity than direct education and the control (discussion) (p<0.001). The single psychological study found relaxation techniques improved clinical severity as compared to the control at 20 weeks (t=2.13) but this was of borderline significance (p=0.042). A lack of rigorously designed trials (excluding one recent German study) provides only limited evidence of the effectiveness of educational and psychological interventions in helping to manage the condition of children with atopic eczema. Evidence from included studies and also adult studies indicates that different service delivery models (multi-professional eczema school and nurse-led clinics) require further and comparative evaluation to examine their cost-effectiveness and suitability for different health systems.

Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.

PubMed

Hussein, Norita; Weng, Stephen F; Kai, Joe; Kleijnen, Jos; Qureshi, Nadeem

2018-03-14

Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. This is an update of a previously published review. To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 20 June 2017.Date of latest search of all other sources: 16 November 2017. Any randomised or quasi-randomised controlled trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease when compared to usual care. We identified 25 papers, describing 16 unique trials which were potentially eligible for inclusion in the review. However, after assessment, no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found. No randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were included. One ongoing trial has been identified which may potentially eligible for inclusion once completed. As no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis, or Tay-Sachs disease were found for inclusion in this review, the research evidence for current policy recommendations is limited to non-randomised studies.Information from well-designed, adequately powered, randomised trials is desirable in order to make more robust recommendations for practice. However, such trials must also consider the legal, ethical, and cultural barriers to implementation of preconception genetic risk assessment.

Structured physical exercise improves neuropsychiatric symptoms in acute dementia care: a hospital-based RCT.

PubMed

Fleiner, Tim; Dauth, Hannah; Gersie, Marleen; Zijlstra, Wiebren; Haussermann, Peter

2017-08-29

The primary objective of this trial is to investigate the effects of a short-term exercise program on neuropsychiatric signs and symptoms in acute hospital dementia care. Within a hospital-based randomized controlled trial, the intervention group conducted a 2-week exercise program with four 20-min exercise sessions on 3 days per week. The control group conducted a social stimulation program. Effects on neuropsychiatric signs and symptoms were measured via the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change, the Neuropsychiatric Inventory, and the Cohen-Mansfield Agitation Inventory. The antipsychotic and sedative dosage was quantified by olanzapine and diazepam equivalents. Eighty-five patients were randomized via minimization to an intervention group (IG) and a control group (CG). Seventy patients (82%) (mean age 80 years, 33 females, mean Mini Mental State Examination score 18.3 points) completed the trial. As compared to the CG (n = 35), the IG (n = 35) showed significantly reduced neuropsychiatric signs and symptoms. Especially, agitated behavior and lability improved. There were no between-group differences concerning antipsychotic and benzodiazepine medication. This exercise program is easily applicable in hospital dementia care and significantly reduces neuropsychiatric signs and symptoms in patients suffering from predominantly moderate stages of dementia. German Clinical Trial Register DRKS00006740 . Registered 28 October 2014.

Cognitive remediation therapy (CRT) as a treatment enhancer of eating disorders and obsessive compulsive disorders: study protocol for a randomized controlled trial.

PubMed

van Passel, Boris; Danner, Unna; Dingemans, Alexandra; van Furth, Eric; Sternheim, Lot; van Elburg, Annemarie; van Minnen, Agnes; van den Hout, Marcel; Hendriks, Gert-Jan; Cath, Daniëlle

2016-11-10

Anorexia nervosa (AN) and Obsessive Compulsive Disorder (OCD) are among the most incapacitating and costly of mental disorders. Cognitive Behaviour Therapy (CBT), medication, and combination regimens, to which in AN personalised guidance on weight control is added, are moderately successful, leaving room for more effective treatment algorithms. An underlying deficit which the two disorders share is cognitive inflexibility, a trait that is likely to impede treatment engagement and reduce patients' ability to benefit from treatment. Cognitive remediation therapy (CRT) is an easy-to-use intervention aimed at reducing cognitive inflexibility and thereby enhancing treatment outcome, which we aim to test in a controled study. In a randomized-controlled multicenter clinical trial 64 adult patients with AN and 64 with OCD are randomized to 10 bi-weekly sessions with either CRT or a control condition, after which Treatment As Usual (TAU) is started. All patients are evaluated during single-blind assessments at baseline, post-CRT/control intervention, and after 6 months. Indices of treatment effect are disorder-specific symptom severity, quality of life, and cost-effectivity. Also, moderators and mediators of treatment effects will be studied. To our knowledge, this is the first randomized controlled trial using an control condition evaluating the efficacy and effectiveness of CRT as a treatment enhancer preceding TAU for AN, and the first study to investigate CRT in OCD, moreover taking cost-effectiveness of CRT in AN and OCD into account. The Netherlands Trial Register NTR3865 . Registered 20 february 2013.

Protocol for a systematic review of psychological interventions for cancer-related fatigue in post-treatment cancer survivors.

PubMed

Corbett, Teresa; Devane, Declan; Walsh, Jane C; Groarke, AnnMarie; McGuire, Brian E

2015-12-04

Fatigue is a common symptom in cancer patients that can persist beyond the curative treatment phase. Some evidence has been reported for interventions for fatigue during active treatment. However, to date, there is no systematic review on psychological interventions for fatigue after the completion of curative treatment for cancer. This is a protocol for a systematic review that aims to evaluate the effectiveness of psychological interventions for cancer-related fatigue in post-treatment cancer survivors. This systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database. We will search the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library), PubMed, MEDLINE, EMBASE, CINAHL, PsycINFO, and relevant sources of grey literature. Randomised controlled trials (RCTs) which have evaluated psychological interventions in adult cancer patients after the completion of treatment, with fatigue as an outcome measure, will be included. Two review authors will independently extract data from the selected studies and assess the methodological quality using the Cochrane Collaboration Risk of Bias Tool. Most existing evidence on cancer-related fatigue is from those in active cancer treatment. This systematic review and meta-analysis will build upon previous evaluations of psychological interventions in people during and after cancer treatment. With the growing need for stage-specific research in cancer, this review seeks to highlight a gap in current practice and to strengthen the evidence base of randomised controlled trials in the area. PROSPERO CRD42014015219.

Preconception lifestyle advice for people with subfertility.

PubMed

Anderson, Kirsty; Norman, Robert J; Middleton, Philippa

2010-04-14

Infertility is a prevalent problem and has significant consequences for individuals, families and the wider community. People's chance of having a healthy, live birth may be impacted upon by factors such as weight, diet, smoking, other substance abuse, environmental pollutants, infections, medical conditions, medications and family medical history. However, there is no current guideline about what preconception advice should be offered to people presenting for infertility treatment. It is important to determine what preconception advice should be given about these types of factors to such people in order to help them to make positive changes and hopefully improve their chances of conception and delivering a healthy, live baby. To assess the effects of preconception advice on the chances of a live birth for people who perceive that they may be infertile and are investigating the possibility of medical treatment to address subfertility. All published and unpublished randomised controlled trials addressing preconception advice to influence lifestyle factors in people who perceived that they may be infertile and investigated the possibility of medical treatment to address subfertility were sought from the Cochrane Menstrual Disorders and Subfertility Review Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library, MEDLINE, PubMed, EMBASE, PsycINFO, AMED, Cumulative Index to Nursing and Allied Health Literature (CINAHL), LILACS, trial registers for ongoing and registered trials, citation indexes, ISI Web of Knowledge, Clinical Study Results database, OpenSIGLE database, China National Knowledge Infrastructure (CNKI) Periodical Index and Google (inception to 5 October 2009). Only randomised controlled trials (RCTs), including cluster-randomised (group-randomised) trials, that considered preconception advice given to individuals who perceived that they may be infertile and were investigating the possibility of medical treatment from subfertility specialist services were eligible for inclusion. The primary outcome was live birth, defined as delivery of a live fetus after 20 completed weeks of gestation. Two review authors independently applied eligibility criteria to, extracted data from and assessed the risk of bias in the single included trial. One trial assessing smoking cessation advice for 94 infertile women smokers fulfilled the criteria for this review, but the trial did not report on the review's primary outcome of live birth or any other fertility-related outcomes. This trial of women attending a fertility clinic showed that smoking cessation advice tailored to a woman's "stage-of-change" (readiness to stop smoking) did not show significant evidence of a difference in stage (including smoking cessation rates) compared with standard clinical advice. No RCTs were located that assessed the effects of preconception advice on the chance of a live birth or other fertility outcomes in people who perceived that they may be infertile and were investigating the possibility of medical treatment to address subfertility. Given the lack of RCTs evaluating the effectiveness of preconception lifestyle advice for people in the afore-mentioned population, this review cannot provide guidance for clinical practice in this area. However, it does highlight the need for further research into this important subject.

Result Publication of Chinese Trials in World Health Organization Primary Registries

PubMed Central

Xuemei, Liu; Youping, Li; Senlin, Yin; Shangqi, Song

2010-01-01

Background Result publication is the key step to improve the transparency of clinical trials. Objective To investigate the result publication rate of Chinese trials registered in World Health Organization (WHO) primary registries. Method We searched 11 WHO primary registries for Chinese trials records. The progress of each trial was analyzed. We searched for the full texts of result publications cited in the registration records. For completed trials without citations, we searched PubMed, Embase, Chinese Biomedical Literature Database (Chinese), China Knowledge Resource Integrated Database, and Chinese Science and Technology Periodicals Database for result publications. The search was conducted on July 14, 2009. We also called the investigators of completed trials to ask about results publication. Results We identified 1294 Chinese trials records (428 in ChiCTR,743 in clinicaltrials.gov,55 in ISRCTN, 21 in ACTRN). A total of 443 trials had been completed. The publication rate of the Chinese trials in WHO primary registries is 35.2%(156/443).The publication rate of Chinese trials in clinicaltrials.gov, ChiCTR, ISRCTN, and ACRTN was 36.5% (53/145), 36.3% (89/245), 26.0%(9/44), and 55.6%(5/9), respectively. The publication rate of trials sponsored by industry(23.8%) was lower than that of sponsored by central and local government(31.7%), hospital(35.1%), and universities (40.7%). The publication rate for randomized trials was higher than that of cohort study and case-control study (33.2% versus 16.7%, 22.2%). The publication rate for interventional studies and observational studies was similar(33.4% versus 33.3%). Conclusion The publication rate of the registered Chinese trials was low, with no significant difference between ChiCTR and clinicaltrials.gov. An effective mechanism is needed to promote publication of results for registered trials in China. PMID:20856888

A Cochrane Systematic Review finds no significant difference in outcome or risk of postoperative complications between day care and in-patient cataract surgery.

PubMed

Fedorowicz, Zbigniew; Lawrence, David J; Gutierrez, Peter

2006-09-01

This review was conducted to determine reliable evidence regarding the safety, feasibility, effectiveness, and cost-effectiveness of cataract extraction performed as a day care versus in-patient procedure. The search to identify randomized controlled trials comparing day care and in-patient surgery for age-related cataract included the Cochrane Eyes and Vision Group Trials Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS Latin American and Caribbean Literature on Health Sciences. Assessment of methodological quality was based on criteria defined by the Cochrane Collaboration. The primary outcome was the achievement of a satisfactory visual acuity 6 weeks after operation. Two trials, involving a total of 1284 people, are included. One trial reported statistically significant differences in early postoperative complication rates in the day care group, which had no clinical relevance to visual outcomes 4 months postoperatively. Mean change in visual acuity Snellen lines of the operated eye 4 months postoperatively was 4.1 standard deviation SD 2.3 for the day care group and 4.1 SD 2.2 for the in-patient group. Costs were 20% more for the in-patient group attributable to higher costs for overnight stay.

A single-blinded, randomized, parallel group superiority trial investigating the effects of footwear and custom foot orthoses versus footwear alone in individuals with patellofemoral joint osteoarthritis: a phase II pilot trial protocol.

PubMed

Wyndow, Narelle; Crossley, Kay M; Vicenzino, Bill; Tucker, Kylie; Collins, Natalie J

2017-01-01

Patellofemoral joint osteoarthritis is a common condition, yet information regarding conservative management is lacking. Foot orthoses are an effective intervention for improving pain and function in younger individuals with patellofemoral pain and may be effective in those with patellofemoral osteoarthritis. This pilot study will seek to establish the feasibility of a phase III randomised controlled trial to investigate whether foot orthoses worn in prescribed motion controlled footwear are superior to prescribed motion control footwear alone in the management of patellofemoral osteoarthritis. This phase II pilot clinical trial is designed as a randomized, single-blind, parallel group, two arm, superiority trial. The trial will recruit 44 participants from Queensland and Tasmania, Australia. Volunteers aged 40 years and over must have clinical symptoms and radiographic evidence of patellofemoral osteoarthritis to be eligible for inclusion. Those eligible will be randomized to receive either foot orthoses and prescribed motion control shoes, or prescribed motion control shoes alone, to be worn for a period of 4 months. The feasibility of a phase III clinical trial will be evaluated by assessing factors such as recruitment rate, number of eligible participants, participant compliance with the study protocol, adverse events, and drop-out rate. A secondary aim of the study will be to determine completion rates and calculate effect sizes for patient reported outcome measures such as knee-related symptoms, function, quality of life, kinesiophobia, self-efficacy, general and mental health, and physical activity at 2 and 4 months. Primary outcomes will be reported descriptively while effect sizes and 95% confidence intervals will be calculated for the secondary outcome measures. Data will be analysed using an intention-to-treat principle. The results of this pilot trial will help determine the feasibility of a phase III clinical trial investigating whether foot orthoses plus motion control footwear are superior to motion control footwear alone in individuals with patellofemoral osteoarthritis. A Phase III clinical trial will help guide footwear and foot orthoses recommendations in the clinical management of this disorder. Retrospectively registered with the Australian New Zealand Clinical Trials Registry: ACTRN12615000002583. Date registered: 07/01/15.

An e-mail survey identified unpublished studies for systematic reviews.

PubMed

Reveiz, Ludovic; Cardona, Andres Felipe; Ospina, Edgar Guillermo; de Agular, Sylvia

2006-07-01

A large number of trials remain difficult to locate or unpublished for systematic reviews. The objective of this article was to determine the usefulness of making e-mail contact with authors of clinical trials and literature reviews found in MEDLINE to identify unpublished or difficult to locate Randomized Controlled Trials (RCTs). A structured search for detecting RCTs in MEDLINE was made from January 1999 to June 2003; a questionnaire was sent to a random sample of 525 author's mails. Those RCTs obtained were sought in MEDLINE, EMBASE, the Cochrane Controlled Trials Register, LILACS, and ongoing registers. 40 (7.6%) replies were received; 10 previously undescribed and unpublished RCTs and 21 unregistered ongoing RCTs were found. The most frequently given reasons for not publishing were: lack of time for finalizing the statistical analysis and preparing the manuscript, contractual obligations with the pharmaceutical industry, methodologic errors in designing, and editorial rejection. Using the e-mails of authors detected by the search in electronic databases could contribute toward detecting potentially relevant ongoing or unpublished RCTs enabling rapid, straightforward, low-cost systematic review; in addition, the results of this study support the need of universal registration of all studies at their inception.

Effectiveness of vocational rehabilitation intervention on the return to work and employment of persons with multiple sclerosis.

PubMed

Khan, Fary; Ng, Louisa; Turner-Stokes, Lynne

2009-01-21

Multiple sclerosis is a neurological disease that frequently affects adults of working age, resulting in a range of physical, cognitive and psychosocial deficits that impact on workforce participation. Although, the literature supports vocational rehabilitation (VR) approaches in persons with multiple sclerosis (pwMS), the evidence for its effectiveness is yet to be established. To evaluate the effectiveness of VR programs compared to alternative programs or care as usual on return to work, workability and employment in pwMS; to evaluate the cost effectiveness of these programs. Electronic searches included: Cochrane Central Register of Controlled Trials "CENTRAL" 2008 issue 3, MEDLINE (PubMed) (1966- 2008), EMBASE (1988- 2008), CINAHL (1982- 2008), PEDro (1990- 2008), the Cochrane Rehabilitation and Related Therapies Field trials Register and the National Health Service National Research Register. Randomized and controlled clinical trials, including before - after controlled trials, that compare VR rehabilitation with alternative intervention such as standard or a lesser form of intervention or waitlist controls. Two reviewers selected trials and rated their methodological quality independently. A 'best evidence' synthesis was performed, based on methodological quality. Trials were grouped in terms of type and setting of VR programs. Two trials (one RCT and one CCT) (total 80 participants) met the review criteria. Both trials scored poorly on the methodological quality assessment. There was 'insufficient evidence' for VR programs for (a)'competitive employment', in altering rates of job retention, changes in employment, improvement in rates of re-entry into the labour force; (b) for altering 'work ability' by improving participants' confidence in the accommodation request process, or employability maturity or job seeking activity. No evidence could be assimilated for changes in proportions of persons in supported employment or on disability pensions, nor for cost-effectiveness. There was inconclusive evidence to support VR for pwMS. However, the review highlights some of the challenges in providing VR for pwMS. Clinicians need to be aware of vocational issues, and to understand and manage barriers for maintaining employment. Proactive and timely VR programs should incorporate practical solutions to deal with work disability, workplace accommodation and educate employers, and the wider community. Liaison with policy makers is imperative for government initiatives that encourage work focused VR programs. Future research in VR should focus on improving methodological and scientific rigour of clinical trials; on the development of appropriate and valid outcome measures; and on cost effectiveness of VR programs.

Virtual reality for stroke rehabilitation: an abridged version of a Cochrane review.

PubMed

Laver, K; George, S; Thomas, S; Deutsch, J E; Crotty, M

2015-08-01

Virtual reality and interactive video gaming have emerged as new treatment approaches in stroke rehabilitation settings over the last ten years. The primary objective of this review was to determine the effectiveness of virtual reality on upper limb function and activity after stroke. The impact on secondary outcomes including gait, cognitive function and activities of daily living was also assessed. Randomized and quasi-randomized controlled trials comparing virtual reality with an alternative intervention or no intervention were eligible to be included in the review. The authors searched a number of electronic databases including: the Cochrane Stroke Group Trials Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED, CINAHL, PsycINFO, clinical trial registers, reference lists, Dissertation Abstracts and contacted key researchers in the field. Search results were independently examined by two review authors to identify studies meeting the inclusion criteria. A total of 37 randomized or quasi randomized controlled trials with a total of 1019 participants were included in the review. Virtual reality was found to be significantly more effective than conventional therapy in improving upper limb function (standardized mean difference [SMD] 0.28, 95% confidence intervals [CI] 0.08 to 0.49) based on 12 studies and significantly more effective than no therapy in improving upper limber function (SMD 0.44 [95% CI 0.15 to 0.73]) based on nine studies. The use of virtual reality also significantly improved activities of daily living function when compared to more conventional therapy approaches (SMD 0.43 [95% CI 0.18 to 0.69]) based on eight studies. While there are a large number of studies assessing the efficacy of virtual reality they tend to be small and many are at risk of bias. While there is evidence to support the use of virtual reality intervention as part of upper limb training programs, more research is required to determine whether it is beneficial in terms of improving lower limb function and gait and cognitive function.

The acute and sub-chronic effects of cocoa flavanols on mood, cognitive and cardiovascular health in young healthy adults: a randomized, controlled trial

PubMed Central

Massee, Laura A.; Ried, Karin; Pase, Matthew; Travica, Nikolaj; Yoganathan, Jaesshanth; Scholey, Andrew; Macpherson, Helen; Kennedy, Greg; Sali, Avni; Pipingas, Andrew

2015-01-01

Cocoa supplementation has been associated with benefits to cardiovascular health. However, cocoa's effects on cognition are less clear. A randomized, placebo-controlled, double-blind clinical trial (n = 40, age M = 24.13 years, SD = 4.47 years) was conducted to investigate the effects of both acute (same-day) and sub-chronic (daily for four-weeks) 250 mg cocoa supplementation on mood and mental fatigue, cognitive performance and cardiovascular functioning in young, healthy adults. Assessment involved repeated 10-min cycles of the Cognitive Demand Battery (CDB) encompassing two serial subtraction tasks (Serial Threes and Sevens), a Rapid Visual Information Processing task, and a mental fatigue scale over the course of half an hour. The Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) was also completed to evaluate cognition. Cardiovascular function included measuring both peripheral and central blood pressure and cerebral blood flow. At the acute time point, consumption of cocoa significantly improved self-reported mental fatigue and performance on the Serial Sevens task in cycle one of the CDB. No other significant effects were found. This trial was registered with the Australian and New Zealand Clinical Trial Registry (Trial ID: ACTRN12613000626763). Accessible via http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12613000626763&ddlSearch=Registered. PMID:26042037

Cardiovascular actions of mineralocorticoid receptor antagonists in patients with chronic kidney disease: A systematic review and meta-analysis of randomized trials.

PubMed

Ng, Khai P; Arnold, Julia; Sharif, Adnan; Gill, Paramjit; Townend, Jonathan N; Ferro, Charles J

2015-09-01

The safety and actions of mineralocorticoid receptor antagonists on surrogate markers of cardiovascular disease as well as major patient level cardiovascular end-points in patients with chronic kidney disease are unclear. MEDLINE, EMBASE, Trip Database, Cochrane Central Register of Controlled Trials, Cochrane Renal Group specialized register, Current Controlled Trials and clinicaltrials.gov were searched for relevant trials. Twenty-nine trials (1581 patients) were included. Overall, mineralocorticoid receptor antagonists lowered both systolic and diastolic blood pressure (-5.24, 95% confidence interval (CI) -8.65, -1.82 mmHg; p=0.003 and -1.96, 95% CI -3.22, -0.69 mmHg; p=0.002 respectively). There were insufficient data to perform a meta-analysis of other cardiovascular effects. However, a systematic review of the studies included suggested a consistent improvement in surrogate markers of cardiovascular disease. Overall, the use of mineralocorticoid receptor antagonists was associated with an increased serum potassium (0.23, 95% CI 0.13, 0.33 mmol/l; p<0.0001) and higher risk ratio (1.76, 95% CI 1.20, 2.57; p=0.001) of hyperkalemia. Data on long-term cardiovascular outcomes and mortality were not available in any of the trials. The long-term effects of mineralocorticoid receptor antagonists on cardiovascular events, mortality and safety need to be established. © The Author(s) 2015.

Omega-3 supplementation to prevent recurrent preterm birth: a systematic review and metaanalysis of randomized controlled trials.

PubMed

Saccone, Gabriele; Berghella, Vincenzo

2015-08-01

The purpose of this study was to evaluate the efficacy of omega-3 supplementation for the prevention of recurrent preterm birth (PTB) in asymptomatic singleton gestations with previous PTB. We searched fish oil, long chain polyunsaturated fatty acids, pregnancy, and omega-3 in MEDLINE, OVID, Scopus, ClinicalTrials.gov, the PROSPERO International Prospective Register of Systematic Reviews, EMBASE, and the Cochrane Central Register of Controlled Trials from inception of each database to December 2014 with no limit for language. In addition the reference lists of all identified articles were examined to identify studies that were not captured by electronic searches. We performed a metaanalysis of randomized controlled trials of asymptomatic singleton gestations with previous PTB who were assigned randomly to prophylactic omega-3 supplementation vs control (either placebo or no treatment). The primary outcome was predefined as PTB at <37 weeks of gestation. The pooled results were reported as relative risk (RR) with 95% confidence interval (95% CI). The protocol of this review was registered with PROSPERO (registration number: CRD42015016371). Two randomized controlled trials that included 1080 women were analyzed. The mean gestational age at randomization was approximately 134 days in both groups (mean difference, 0.01 days; 95% CI, -0.13 to 0.14). Women who received omega-3 had similar rates of PTB at <37 weeks of gestation (34.5% vs 39.8%; RR, 0.81; 95% CI, 0.59-1.12) and PTB at <34 weeks of gestation (12.0% vs 15.4%; RR, 0.62; 95% CI, 0.26-1.46) compared with control subjects. The omega-3 groups had a statistically significantly longer latency (mean difference, 2.10 days; 95% CI, 1.98-2.22) and higher birthweight (mean difference, 102.52 g; 95% CI, 20.09-184.95) compared with control subjects; the other secondary outcomes (which included gestational age at delivery, spontaneous PTB at <37 and 34 weeks of gestation, admission to the intensive care unit, intraventricular hemorrhage, necrotizing enterocolitis, sepsis, and perinatal death) were similar. Omega-3 supplementation during pregnancy does not prevent recurrent PTB in asymptomatic singleton gestations with previous PTB. The benefits in longer latency and higher birth weight may deserve further study. Copyright © 2015 Elsevier Inc. All rights reserved.

Interventions for improving patients' trust in doctors and groups of doctors.

PubMed

Rolfe, Alix; Cash-Gibson, Lucinda; Car, Josip; Sheikh, Aziz; McKinstry, Brian

2014-03-04

Trust is a fundamental component of the patient-doctor relationship and is associated with increased satisfaction, adherence to treatment, and continuity of care. Our 2006 review found little evidence that interventions improve patients' trust in their doctor; therefore an updated search was required to find out if there is further evidence of the effects of interventions that may improve trust in doctors or groups of doctors. To update our earlier review assessing the effects of interventions intended to improve patients' trust in doctors or a group of doctors. In 2003 we searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, EMBASE, Health Star, PsycINFO, CINAHL, LILACS, African Trials Register, African Health Anthology, Dissertation Abstracts International and the bibliographies of studies selected for inclusion. We also contacted researchers active in the field. We updated and re-ran the searches on available original databases (Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library issue 2, 2013), MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP), CINAHL (Ebsco)) as well as Proquest Dissertations and Current Contents for the period 2003 to 18 March 2013. Randomised controlled trials (RCTs), quasi-randomised controlled trials, controlled before and after studies, and interrupted time series of interventions (informative, educational, behavioural, organisational) directed at doctors or patients (or carers) where trust was assessed as a primary or secondary outcome. Two review authors independently extracted data and assessed the risk of bias of included studies. Where mentioned, we extracted data on adverse effects. We synthesised data narratively. We included 10 randomised controlled trials (including 7 new trials) involving 11,063 patients. These studies were all undertaken in North America, and all but two involved primary care.  As expected, there was considerable heterogeneity between the studies.  Interventions were of three main types; three employed additional physician training, four were education for patients and three provided additional information about doctors in terms of financial incentives or consulting style. Additionally, several different measures of trust were employed.The studies gave conflicting results. Trials showing a small but statistically-significant increase in trust included: a trial of physician disclosure of financial incentives; a trial of providing choice of physician based on concordance between patient and physician beliefs about care; a trial of group visits for new inductees into a Health Maintenance Organisation; a trial of training oncologists in communication skills; and a trial of group visits for diabetic patients. However, trust was not affected in a subsequent larger trial of group visits for uninsured people with diabetes, nor with a decision aid for helping choose statins, another trial of disclosure of financial incentives or specifically training doctors to increase trust or cultural competence. There was no evidence of harm from any of the studies. Overall, there remains insufficient evidence to conclude that any intervention may increase or decrease trust in doctors. This may be due in part to the sensitivity of trust instruments, and a ceiling effect, as trust in doctors is generally high. It may be that current measures of trust are insufficiently sensitive. Further trials are required to explore the impact of doctors' specific training or the use of a patient-centred or decision-sharing approach on patients' trust, especially in the areas of healthcare provider choice, and induction into healthcare organisation. International trials would be of particular benefit. The review was constrained by the lack of consistency between trust measurements, timeframes and populations.

Surgery for post-vitrectomy cataract

PubMed Central

Do, Diana V; Gichuhi, Stephen; Vedula, Satyanarayana S; Hawkins, Barbara S

2014-01-01

Background Cataract formation or acceleration can occur after intraocular surgery, especially following vitrectomy, a surgical technique for removing the vitreous which is used in the treatment of disorders that affect the posterior segment of the eye. The underlying problem that led to vitrectomy may limit the benefit from cataract surgery. Objectives The objective of this review was to evaluate the effectiveness and safety of surgery for post-vitrectomy cataract with respect to visual acuity, quality of life, and other outcomes. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 4), Ovid MEDLINE, Ovid MEDLINE in-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily Update, Ovid OLDMED-LINE (January 1946 to May 2013), EMBASE (January 1980 to May 2013, Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to May 2013), PubMed (January 1946 to May 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrial.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 22 May 2013. Selection criteria We planned to include randomized and quasi-randomized controlled trials comparing cataract surgery with no surgery in adult patients who developed cataract following vitrectomy. Data collection and analysis Two authors screened the search results independently according to the standard methodological procedures expected by The Cochrane Collaboration. Main results We found no randomized or quasi-randomized controlled trials comparing cataract surgery with no cataract surgery for patients who developed cataracts following vitrectomy surgery. Authors' conclusions There is no evidence from randomized or quasi-randomized controlled trials on which to base clinical recommendations for surgery for post-vitrectomy cataract. There is a clear need for randomized controlled trials to address this evidence gap. Such trials should stratify participants by their age, the retinal disorder leading to vitrectomy, and the status of the underlying disease process in the contralateral eye. Outcomes assessed in such trials may include gain of vision on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, quality of life, and adverse events such as posterior capsular rupture. Both short-term (six-month) and long-term (one-year or two-year) outcomes should be examined. PMID:24357418

Cutaneous lichen planus: A systematic review of treatments.

PubMed

Fazel, Nasim

2015-06-01

Various treatment modalities are available for cutaneous lichen planus. Pubmed, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database were searched for all the systematic reviews and randomized controlled trials related to cutaneous lichen planus. Two systematic reviews and nine relevant randomized controlled trials were identified. Acitretin, griseofulvin, hydroxychloroquine and narrow band ultraviolet B are demonstrated to be effective in the treatment of cutaneous lichen planus. Sulfasalazine is effective, but has an unfavorable safety profile. KH1060, a vitamin D analogue, is not beneficial in the management of cutaneous lichen planus. Evidence from large scale randomized trials demonstrating the safety and efficacy for many other treatment modalities used to treat cutaneous lichen planus is simply not available.

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI).

PubMed

Kwan, I; Bhattacharya, S; McNeil, A; van Rumste, M M E

2008-04-16

Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation (IVF) treatment has included ultrasonography plus serum estradiol concentration to ensure safe practice by reducing the incidence and severity of ovarian hyperstimulation syndrome (OHSS). The need for intensive monitoring during ovarian stimulation in IVF is controversial. It has been suggested that close monitoring is time consuming, expensive and inconvenient for the woman and simplification of IVF therapy by using ultrasound only should be considered. This systematic review assessed the effects of ovarian monitoring by ultrasound only versus ultrasound plus serum estradiol measurement on IVF outcomes and the occurrence of OHSS in women undergoing stimulated cycles in IVF and intra-cytoplasmic sperm injection (ICSI) treatment. To quantify the effect of monitoring controlled ovarian stimulation in IVF and ICSI cycles with ultrasound plus serum estradiol concentration versus ultrasound only in terms of live birth rates, pregnancy rates and the incidence of OHSS. We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL) on the latest issue of The Cochrane Library, MEDLINE (1966 to May 2007), EMBASE (1980 to May 2007), CINAHL (1982 to May 2007), the National Research Register, and web-based trial databases such as Current Controlled Trials. There was no language restriction. Additionally all references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data. Only randomised controlled trials that compared monitoring with ultrasound plus serum estradiol concentration versus ultrasound only in women undergoing ovarian hyperstimulation for IVF and ICSI treatment were included. Two review authors independently examined the electronic search results for relevant trials, extracted data and assessed trial quality. They resolved disagreements by discussion with two other authors. Outcomes data were pooled when appropriate and summary statistics presented when limited data did not allow meta-analysis. Our search strategy identified 1119 potentially eligible reports, of which two met our inclusion criteria. These involved 411 women who underwent controlled ovarian stimulation monitoring. Our primary outcome of live birth rate was not reported in either study. One trial reported clinical pregnancy rate per woman (33% versus 31%; RR 1.07, 95% CI 0.77 to 1.49), the second trial reported clinical pregnancy rate per oocyte retrieval (22% versus 25%). There was no significant difference between the ultrasound plus estradiol group and the ultrasound alone group in the mean number of oocytes retrieved (WMD -0.55, 95% CI -1.79 to 0.69) and the incidence of ovarian hyperstimulation (RR 0.73, 95% CI 0.30 to 1.78) for the two studies. There is no evidence from randomised trials to support cycle monitoring by ultrasound plus serum estradiol as more efficacious than cycle monitoring by ultrasound only on outcomes of live birth and pregnancy rates. A large well-designed randomised controlled trial is needed that reports on live birth rates and pregnancy, with economic evaluation of the costs involved and the views of the women undergoing cycle monitoring. A randomised trial with sufficiently large sample size to test the effects of different monitoring protocols on OHSS, a rare outcome, will pose a great challenge. Until such a trial is considered feasible, cycle monitoring by transvaginal ultrasound plus serum estradiol may need to be retained as a precautionary good practice point.

Funding source and primary outcome changes in clinical trials registered on ClinicalTrials.gov are associated with the reporting of a statistically significant primary outcome: a cross-sectional study.

PubMed

Ramagopalan, Sreeram V; Skingsley, Andrew P; Handunnetthi, Lahiru; Magnus, Daniel; Klingel, Michelle; Pakpoor, Julia; Goldacre, Ben

2015-01-01

We and others have shown a significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. The objectives of this study were to investigate whether changes made to primary outcomes are associated with the likelihood of reporting a statistically significant primary outcome on ClinicalTrials.gov. A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 20 November 2014 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date. 13,238 completed interventional trials were registered with ClinicalTrials.gov that also had study results posted on the website. 2555 (19.3%) had one or more statistically significant primary outcomes. Statistical analysis showed that registration year, funding source and primary outcome change after trial completion were associated with reporting a statistically significant primary outcome .  Funding source and primary outcome change after trial completion are associated with a statistically significant primary outcome report on clinicaltrials.gov.

COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): statistical and economic analysis plan for a randomised controlled trial.

PubMed

Robinson, Emily J; Goldstein, Laura H; McCrone, Paul; Perdue, Iain; Chalder, Trudie; Mellers, John D C; Richardson, Mark P; Murray, Joanna; Reuber, Markus; Medford, Nick; Stone, Jon; Carson, Alan; Landau, Sabine

2017-06-06

Dissociative seizures (DSs), also called psychogenic non-epileptic seizures, are a distressing and disabling problem for many patients in neurological settings with high and often unnecessary economic costs. The COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES) trial is an evaluation of a specifically tailored psychological intervention with the aims of reducing seizure frequency and severity and improving psychological well-being in adults with DS. The aim of this paper is to report in detail the quantitative and economic analysis plan for the CODES trial, as agreed by the trial steering committee. The CODES trial is a multicentre, pragmatic, parallel group, randomised controlled trial performed to evaluate the clinical effectiveness and cost-effectiveness of 13 sessions of cognitive behavioural therapy (CBT) plus standardised medical care (SMC) compared with SMC alone for adult outpatients with DS. The objectives and design of the trial are summarised, and the aims and procedures of the planned analyses are illustrated. The proposed analysis plan addresses statistical considerations such as maintaining blinding, monitoring adherence with the protocol, describing aspects of treatment and dealing with missing data. The formal analysis approach for the primary and secondary outcomes is described, as are the descriptive statistics that will be reported. This paper provides transparency to the planned inferential analyses for the CODES trial prior to the extraction of outcome data. It also provides an update to the previously published trial protocol and guidance to those conducting similar trials. ISRCTN registry ISRCTN05681227 (registered on 5 March 2014); ClinicalTrials.gov NCT02325544 (registered on 15 December 2014).

Lee Silverman Voice Treatment versus standard speech and language therapy versus control in Parkinson's disease: a pilot randomised controlled trial (PD COMM pilot).

PubMed

Sackley, Catherine M; Smith, Christina H; Rick, Caroline E; Brady, Marian C; Ives, Natalie; Patel, Smitaa; Woolley, Rebecca; Dowling, Francis; Patel, Ramilla; Roberts, Helen; Jowett, Sue; Wheatley, Keith; Kelly, Debbie; Sands, Gina; Clarke, Carl E

2018-01-01

Speech-related problems are common in Parkinson's disease (PD), but there is little evidence for the effectiveness of standard speech and language therapy (SLT) or Lee Silverman Voice Treatment (LSVT LOUD®). The PD COMM pilot was a three-arm, assessor-blinded, randomised controlled trial (RCT) of LSVT LOUD®, SLT and no intervention (1:1:1 ratio) to assess the feasibility and to inform the design of a full-scale RCT. Non-demented patients with idiopathic PD and speech problems and no SLT for speech problems in the past 2 years were eligible. LSVT LOUD® is a standardised regime (16 sessions over 4 weeks). SLT comprised individualised content per local practice (typically weekly sessions for 6-8 weeks). Outcomes included recruitment and retention, treatment adherence, and data completeness. Outcome data collected at baseline, 3, 6, and 12 months included patient-reported voice and quality of life measures, resource use, and assessor-rated speech recordings. Eighty-nine patients were randomised with 90% in the therapy groups and 100% in the control group completing the trial. The response rate for Voice Handicap Index (VHI) in each arm was ≥ 90% at all time-points. VHI was highly correlated with the other speech-related outcome measures. There was a trend to improvement in VHI with LSVT LOUD® (difference at 3 months compared with control: - 12.5 points; 95% CI - 26.2, 1.2) and SLT (difference at 3 months compared with control: - 9.8 points; 95% CI - 23.2, 3.7) which needs to be confirmed in an adequately powered trial. Randomisation to a three-arm trial of speech therapy including a no intervention control is feasible and acceptable. Compliance with both interventions was good. VHI and other patient-reported outcomes were relevant measures and provided data to inform the sample size for a substantive trial. International Standard Randomised Controlled Trial Number Register: ISRCTN75223808. registered 22 March 2012.

Disposable surgical face masks for preventing surgical wound infection in clean surgery.

PubMed

Vincent, Marina; Edwards, Peggy

2016-04-26

Surgical face masks were originally developed to contain and filter droplets containing microorganisms expelled from the mouth and nasopharynx of healthcare workers during surgery, thereby providing protection for the patient. However, there are several ways in which surgical face masks could potentially contribute to contamination of the surgical wound, e.g. by incorrect wear or by leaking air from the side of the mask due to poor string tension. To determine whether the wearing of disposable surgical face masks by the surgical team during clean surgery reduces postoperative surgical wound infection. In December 2015, for this seventh update, we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials; Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. We also searched the bibliographies of all retrieved and relevant publications. There were no restrictions with respect to language, date of publication or study setting. Randomised controlled trials (RCTs) and quasi-randomised controlled trials comparing the use of disposable surgical masks with the use of no mask. Two review authors extracted data independently. We included three trials, involving a total of 2106 participants. There was no statistically significant difference in infection rates between the masked and unmasked group in any of the trials. We identified no new trials for this latest update. From the limited results it is unclear whether the wearing of surgical face masks by members of the surgical team has any impact on surgical wound infection rates for patients undergoing clean surgery.

Negative pressure wound therapy for partial-thickness burns.

PubMed

Dumville, Jo C; Munson, Christopher

2012-12-12

A burn wound is a complex and evolving injury, with both local and systemic consequences. Burn treatments include a variety of dressings, as well as newer strategies, such as negative pressure wound therapy (NPWT), which, by means of a suction force that drains excess fluids from the burn, tries to promote the wound healing process and minimise progression of the burn wound. To assess the effectiveness of NPWT for people with partial-thickness burns. For this third update we searched the Cochrane Wounds Group Specialised Register (searched 18 May 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5); Ovid MEDLINE (2010 to May Week 2 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 17 May 2012); Ovid EMBASE (2010 to 2012 Week 19); and EBSCO CINAHL (2010 to 16 May 2012). All randomised controlled trials (RCTs) and controlled clinical trials (CCTs) that evaluated the safety and effectiveness of NPWT for partial-thickness burns. Two review authors used standardised forms, and extracted the data independently. We assessed each trial for risk of bias, and resolved differences by discussion. One RCT, that was an interim report, satisfied the inclusion criteria. We undertook a narrative synthesis of results, as the absence of data and poor reporting precluded us from carrying out any formal statistical analysis. The trial was at high risk of bias. There was not enough evidence available to permit any conclusions to be drawn regarding the use of NPWT for treatment of partial-thickness burn wounds.

Antibiotics for the prophylaxis of bacterial endocarditis in dentistry.

PubMed

Glenny, Anne-Marie; Oliver, Richard; Roberts, Graham J; Hooper, Lee; Worthington, Helen V

2013-10-09

Infective endocarditis is a severe infection arising in the lining of the chambers of the heart with a high mortality rate.Many dental procedures cause bacteraemia and it was believed that this may lead to bacterial endocarditis (BE) in a few people. Guidelines in many countries have recommended that prior to invasive dental procedures antibiotics are administered to people at high risk of endocarditis. However, recent guidance by the National Institute for Health and Care Excellence (NICE) in England and Wales has recommended that antibiotics are not required. To determine whether prophylactic antibiotic administration, compared to no such administration or placebo, before invasive dental procedures in people at risk or at high risk of bacterial endocarditis influences mortality, serious illness or the incidence of endocarditis. The following electronic databases were searched: the Cochrane Oral Health Group's Trials Register (to 21 January 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 12), MEDLINE via OVID (1946 to 21 January 2013) and EMBASE via OVID (1980 to 21 January 2013). We searched for ongoing trials in the US National Institutes of Health Trials Register (http://clinicaltrials.gov) and the metaRegister of Controlled Trials (http://www.controlled-trials.com/mrct/). No restrictions were placed on the language or date of publication when searching the electronic databases. Due to the low incidence of BE it was anticipated that few if any trials would be located. For this reason, cohort and case-control studies were included where suitably matched control or comparison groups had been studied. The intervention was the administration of antibiotic, compared to no such administration, before a dental procedure in people with an increased risk of BE. Cohort studies would need to follow those individuals at increased risk and assess outcomes following any invasive dental procedures, grouping by whether prophylaxis was received or not. Included case-control studies would need to match people who had developed endocarditis (and who were known to be at increased risk before undergoing an invasive dental procedure preceding the onset of endocarditis) with those at similar risk but who had not developed endocarditis. Outcomes of interest were mortality or serious adverse events requiring hospital admission; development of endocarditis following any dental procedure in a defined time period; development of endocarditis due to other non-dental causes; any recorded adverse events to the antibiotics; and cost implications of the antibiotic provision for the care of those patients who developed endocarditis. Two review authors independently selected studies for inclusion then assessed risk of bias and extracted data from the included study. No randomised controlled trials (RCTs), controlled clinical trials (CCTs) or cohort studies were included. One case-control study met the inclusion criteria. It collected all the cases of endocarditis in the Netherlands over two years, finding a total of 24 people who developed endocarditis within 180 days of an invasive dental procedure, definitely requiring prophylaxis according to current guidelines, and who were at increased risk of endocarditis due to a pre-existing cardiac problem. This study included participants who died because of the endocarditis (using proxies). Controls attended local cardiology outpatient clinics for similar cardiac problems, had undergone an invasive dental procedure within the past 180 days, and were matched by age with the cases. No significant effect of penicillin prophylaxis on the incidence of endocarditis could be seen. No data were found on other outcomes. There remains no evidence about whether antibiotic prophylaxis is effective or ineffective against bacterial endocarditis in people at risk who are about to undergo an invasive dental procedure. It is not clear whether the potential harms and costs of antibiotic administration outweigh any beneficial effect. Ethically, practitioners need to discuss the potential benefits and harms of antibiotic prophylaxis with their patients before a decision is made about administration.

Immediate versus delayed loading of strategic mini dental implants for the stabilization of partial removable dental prostheses: a patient cluster randomized, parallel-group 3-year trial.

PubMed

Mundt, Torsten; Al Jaghsi, Ahmad; Schwahn, Bernd; Hilgert, Janina; Lucas, Christian; Biffar, Reiner; Schwahn, Christian; Heinemann, Friedhelm

2016-07-30

Acceptable short-term survival rates (>90 %) of mini-implants (diameter < 3.0 mm) are only documented for mandibular overdentures. Sound data for mini-implants as strategic abutments for a better retention of partial removable dental prosthesis (PRDP) are not available. The purpose of this study is to test the hypothesis that immediately loaded mini-implants show more bone loss and less success than strategic mini-implants with delayed loading. In this four-center (one university hospital, three dental practices in Germany), parallel-group, controlled clinical trial, which is cluster randomized on patient level, a total of 80 partially edentulous patients with unfavourable number and distribution of remaining abutment teeth in at least one jaw will receive supplementary min-implants to stabilize their PRDP. The mini-implant are either immediately loaded after implant placement (test group) or delayed after four months (control group). Follow-up of the patients will be performed for 36 months. The primary outcome is the radiographic bone level changes at implants. The secondary outcome is the implant success as a composite variable. Tertiary outcomes include clinical, subjective (quality of life, satisfaction, chewing ability) and dental or technical complications. Strategic implants under an existing PRDP are only documented for standard-diameter implants. Mini-implants could be a minimal invasive and low cost solution for this treatment modality. The trial is registered at Deutsches Register Klinischer Studien (German register of clinical trials) under DRKS-ID: DRKS00007589 ( www.germanctr.de ) on January 13(th), 2015.

Study protocol: a randomized controlled trial investigating the effects of a psychosexual training program for adolescents with autism spectrum disorder.

PubMed

Visser, Kirsten; Greaves-Lord, Kirstin; Tick, Nouchka T; Verhulst, Frank C; Maras, Athanasios; van der Vegt, Esther J M

2015-08-28

Previous research shows that adolescents with autism spectrum disorder (ASD) run several risks in their psychosexual development and that these adolescents can have limited access to reliable information on puberty and sexuality, emphasizing the need for specific guidance of adolescents with ASD in their psychosexual development. Few studies have investigated the effects of psychosexual training programs for adolescents with ASD and to date no randomized controlled trials are available to study the effects of psychosexual interventions for this target group. The randomized controlled trial (RCT) described in this study protocol aims to investigate the effects of the Tackling Teenage Training (TTT) program on the psychosexual development of adolescents with ASD. This parallel clinical trial, conducted in the South-West of the Netherlands, has a simple equal randomization design with an intervention and a waiting-list control condition. Two hundred adolescents and their parents participate in this study. We assess the participants in both conditions using self-report as well as parent-report questionnaires at three time points during 1 year: at baseline (T1), post-treatment (T2), and for follow-up (T3). To our knowledge, the current study is the first that uses a randomized controlled design to study the effects of a psychosexual training program for adolescents with ASD. It has a number of methodological strengths, namely a large sample size, a wide range of functionally relevant outcome measures, the use of multiple informants, and a standardized research and intervention protocol. Also some limitations of the described study are identified, for instance not making a comparison between two treatment conditions, and no use of blinded observational measures to investigate the ecological validity of the research results. Dutch Trial Register NTR2860. Registered on 20 April 2011.

Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults.

PubMed

Hall, Deborah A; Haider, Haula; Szczepek, Agnieszka J; Lau, Pia; Rabau, Sarah; Jones-Diette, Julie; Londero, Alain; Edvall, Niklas K; Cederroth, Christopher R; Mielczarek, Marzena; Fuller, Thomas; Batuecas-Caletrio, Angel; Brueggemen, Petra; Thompson, Dean M; Norena, Arnaud; Cima, Rilana F F; Mehta, Rajnikant L; Mazurek, Birgit

2016-06-01

There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525 . Registered on 12 March 2015 revised on 15 March 2016.

Antibiotic therapy for Shigella dysentery.

PubMed

Prince Christopher R H; David, Kirubah V; John, Sushil M; Sankarapandian, Venkatesan

2010-01-20

Shigella dysentery is a relatively common illness and occasionally causes death, worldwide. Mild symptoms are self-limiting but in more severe cases, antibiotics are recommended for cure and preventing relapse. The antibiotics recommended are diverse, have regional differences in sensitivity, and have side effects. To evaluate the efficacy and safety of antibiotics for treating Shigella dysentery. In June 2009 we identified all relevant trials from the following databases: Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, issue 4), MEDLINE, EMBASE, LILACS and the metaRegister of Controlled Trials (mRCT). We also checked conference proceedings for relevant abstracts, and contacted researchers, organizations, and pharmaceutical companies. Randomized controlled trials of antibiotics for Shigella dysentery. Four authors, working in pairs, independently assessed trial eligibility, methodological quality, and extracted data. We calculated risk ratios (RR) with 95% confidence intervals (CI) for dichotomous data, and used the random-effects model for significant heterogeneity. We explored possible sources of heterogeneity, when present, in subgroup analyses of participant age and percentage of participants with confirmed Shigella infection. Sixteen trials (1748 participants), spanning four decades and with differing sensitivity to Shigella isolates, met the inclusion criteria. Seven were judged to be at risk of bias due to inadequate allocation concealment or blinding, and 12 due to incomplete reporting of outcome data. Limited data from one three-armed trial of people with moderately severe illness suggest that antibiotics reduce the episodes of diarrhoea at follow-up (furazolidone versus no drug RR 0.21, 95% CI 0.09 to 0.48, 73 participants; cotrimoxazole versus no drug RR 0.30, 95% CI 0.15 to 0.59, 76 participants).There was insufficient evidence to consider any class of antibiotic superior in efficacy in treating Shigella dysentery, but heterogeneity for some comparisons limits confidence in the results. All the antibiotics studied were safe. There was inadequate evidence regarding the role of antibiotics in preventing relapses. Antibiotics reduce the duration of Shigella dysentery.Regularly updated local or regional antibiotic sensitivity patterns to different species and strains of Shigella are required to guide empiric therapy. More trials adhering to standard guidelines are required to evaluate the role of antibiotics in the treatment of severe forms of Shigella dysentery and in groups who are at high risk of complications.

Antibiotic therapy for Shigella dysentery.

PubMed

Christopher, Prince Rh; David, Kirubah V; John, Sushil M; Sankarapandian, Venkatesan

2010-08-04

Shigella dysentery is a relatively common illness and occasionally causes death, worldwide. Mild symptoms are self-limiting but in more severe cases, antibiotics are recommended for cure and preventing relapse. The antibiotics recommended are diverse, have regional differences in sensitivity, and have side effects. To evaluate the efficacy and safety of antibiotics for treating Shigella dysentery. In June 2009 we identified all relevant trials from the following databases: Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, issue 4), MEDLINE, EMBASE, LILACS and the metaRegister of Controlled Trials (mRCT). We also checked conference proceedings for relevant abstracts, and contacted researchers, organizations, and pharmaceutical companies. Randomized controlled trials of antibiotics for Shigella dysentery. Four authors, working in pairs, independently assessed trial eligibility, methodological quality, and extracted data. We calculated risk ratios (RR) with 95% confidence intervals (CI) for dichotomous data, and used the random-effects model for significant heterogeneity. We explored possible sources of heterogeneity, when present, in subgroup analyses of participant age and percentage of participants with confirmed Shigella infection. Sixteen trials (1748 participants), spanning four decades and with differing sensitivity to Shigella isolates, met the inclusion criteria. Seven were judged to be at risk of bias due to inadequate allocation concealment or blinding, and 12 due to incomplete reporting of outcome data. Limited data from one three-armed trial of people with moderately severe illness suggest that antibiotics reduce the episodes of diarrhoea at follow-up (furazolidone versus no drug RR 0.21, 95% CI 0.09 to 0.48, 73 participants; cotrimoxazole versus no drug RR 0.30, 95% CI 0.15 to 0.59, 76 participants).There was insufficient evidence to consider any class of antibiotic superior in efficacy in treating Shigella dysentery, but heterogeneity for some comparisons limits confidence in the results. All the antibiotics studied were safe. There was inadequate evidence regarding the role of antibiotics in preventing relapses. Antibiotics reduce the duration of Shigella dysentery.Regularly updated local or regional antibiotic sensitivity patterns to different species and strains of Shigella are required to guide empiric therapy. More trials adhering to standard guidelines are required to evaluate the role of antibiotics in the treatment of severe forms of Shigella dysentery and in groups who are at high risk of complications.

Effectiveness and safety of moderate-intensity aerobic water exercise during pregnancy for reducing use of epidural analgesia during labor: protocol for a randomized clinical trial.

PubMed

Navas, Araceli; Artigues, Catalina; Leiva, Alfonso; Portells, Elena; Soler, Aina; Cladera, Antonia; Ortas, Silvia; Alomar, Margarita; Gual, Marina; Manzanares, Concepción; Brunet, Marina; Julià, Magdalena; López, Lidia; Granda, Lorena; Bennasar-Veny, Miquel; Carrascosa, Mari Carmen

2018-04-11

Epidural analgesia during labor can provide effective pain relief, but can also lead to adverse effects. The practice of moderate exercise during pregnancy is associated with an increased level of endorphins in the blood, and this could also provide pain relief during labor. Aerobic water exercises, rather than other forms of exercise, do not negatively impact articulations, reduce edema, blood pressure, and back pain, and increase diuresis. We propose a randomized controlled trial (RCT) to evaluate the effectiveness and safety of a moderate water exercise program during pregnancy on the need for epidural analgesia during labor. A multi-center, parallel, randomized, evaluator blinded, controlled trial in a primary care setting. We will randomised 320 pregnant women (14 to 20 weeks gestation) who have low risk of complications to a moderate water exercise program or usual care. The findings of this research will contribute toward understanding of the effects of a physical exercise program on pain and the need for analgesia during labor. ISRCTN Registry identifier: 14097513 register on 04 September 2017. Retrospectively registered.

Prevalence of primary outcome changes in clinical trials registered on ClinicalTrials.gov: a cross-sectional study.

PubMed

Ramagopalan, Sreeram; Skingsley, Andrew P; Handunnetthi, Lahiru; Klingel, Michelle; Magnus, Daniel; Pakpoor, Julia; Goldacre, Ben

2014-01-01

An important principle in the good conduct of clinical trials is that a summary of the trial protocol, with a pre-defined primary outcome, should be freely available before the study commences. The clinical trials registry ClinicalTrials.gov provides one method of doing this, and once the trial is registered, any changes made to the primary outcome are documented. The objectives of this study were: to assess the proportion of registered trials on ClinicalTrials.gov that had the primary outcome changed; to assess when the primary outcome was changed in relation to the listed study start and end dates and to assess whether the primary outcome change had any relation to the study sponsor. A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 25 October 2012 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date. Our analysis showed that 28229 of 89204 (31.7%) registered studies had their primary outcome changed.  Industry funding was associated with all primary outcome changes, odds ratio (OR)= 1.36, 95% confidence interval (CI)=1.31-1.41, p<0.001; with primary outcome changes after study start date OR=1.37, 95% CI=1.32-1.42, p<0.001; with primary outcome changes after primary completion date OR=1.84, 95% CI=1.75-1.94, p<0.001 and with primary outcome changes after study completion date OR=1.82, 95% CI=1.73-1.91, p<0.001.  Conclusions A significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. These changes are associated with funding source.

Effects of a mobility monitoring system on the cost of care in relation to reimbursement at Swiss nursing homes: learnings from a randomized controlled trial.

PubMed

Stark, Mario; Tietz, Rigo; Gattinger, Heidrun; Hantikainen, Virpi; Ott, Stefan

2017-12-01

Nursing homes in Switzerland are under pressure to efficiently coordinate staff activities to cover their personnel costs under the care financing system. In this study, the use of a mobility monitoring system accompanied with case conferences was investigated in order to improve sleep quality and estimate the cost benefit of this intervention. In an open two-phase randomized controlled trial at three nursing homes, residents with cognitive impairment were randomly assigned to an intervention group and a control group. In the intervention group, a 10-week period of intensive use of the monitoring system and case conferences led by an advanced nurse practitioner (Phase I) was followed by 3 months of reduced use of the monitoring system and case conferences led by an internal registered nurse (Phase II). In the control group, the monitoring system was only used for data acquisition. Nurses reported the activities with a specifically developed tool. Based on the recorded activities, the cost of care was calculated. The correlating reimbursement per patient was calculated from the care levels in the Swiss reimbursement system. Data from 44 residents was included in the analysis with a linear mixed model. Although analysis revealed no statistically significant effects, results indicate that the use of a monitoring system can guide nurses in organizing their tasks to increase effectiveness. Information systems such as the mobility monitor can help to identify single outliers that do not correspond with the overall situation. In the health care system, problematic individual cases can account for a disproportionally high cost levels. It was shown that information systems can have a significant economic impact in the long run. The study is registered at the German Clinical Trials Register under the Nr. DRKS00006829 .

Preoperative endoscopic titanium clip placement facilitates intraoperative localization of early-stage esophageal cancer or severe dysplasia.

PubMed

Tan, Lei; Feng, Juan; Zhao, Qin; Chen, Ping; Yang, Guotao

2017-08-02

Accurate intraoperative localization of esophageal lesions is essential for successful surgical resection. We tested whether preoperative endoscopic placement of titanium clips could facilitate intraoperative localization of early-stage esophageal cancer or severe dysplasia. A prospective randomized clinical trial was performed between May 2012 and July 2014. All enrolled patients received preoperative endoscopy and esophageal endoscopic ultrasound, as well as pathological study on the biopsy specimen, to confirm early stage esophageal cancer or severe dysplasia. One day before the surgical operation, patients in the experimental group received the preoperative endoscopic titanium labeling of esophageal lesions. Then, during the surgical operation, palpitation of titanium clips was used to localize the lesions in these patients. In patients in the control group, palpitation of nodules or esophageal wall mucosal thickening, together with the consideration of the results from preoperative endoscopic and ultrasound studies, was applied to estimate the location of the esophageal lesions. Study outcomes included the proportions of patients having successful intraoperative pre-resection lesion localization, post-esophagectomy lesion visualization, negative upper surgical margin, change of surgical approaches, and positive postoperative pathological diagnosis. A total of 27 patients were enrolled into the study, with 14 in the experimental group and 13 in the control group. Compared to the patients in the control group, a higher proportion of patients in the experimental group had statistically significant successful intraoperative esophageal lesion localization (100 versus 15.3% in the experimental versus control group). Preoperative endoscopic titanium clip placement could facilitate intraoperative localization of early-stage esophageal cancer or severe dysplasia. Current study was registered in Chinese Clinical Trial Registry and World Health Organization International Clinical Trials Registry Platform, ChiCTR-INR-17010949 . Registered 22 March 2017, retrospectively registered.

The Characteristics of TCM Clinical Trials: A Systematic Review of ClinicalTrials.gov.

PubMed

Chen, Junchao; Huang, Jihan; Li, Jordan V; Lv, Yinghua; He, Yingchun; Zheng, Qingshan

2017-01-01

The aim of this review is to characterize current status of global TCM clinical trials registered in ClinicalTrials.gov. We examined all the trials registered within ClinicalTrials.gov up to 25 September 2015, focusing on study interventions to identify TCM-related trials, and extracted 1,270 TCM trials from the data set. Overall, 691 (54.4%) trials were acupuncture, and 454 (35.8%) trials were herbal medicines. Differences in TCM trial intervention types were also evident among the specific therapeutic areas. Among all trials, 55.7% that were small studies enrolled <100 subjects, and only 8.7% of completed studies had reported results of trials. As for the location, the United States was second to China in conducting the most TCM trials. This review is the first snapshot of the landscape of TCM clinical trials registered in ClinicalTrials.gov, providing the basis for treatment and prevention of diseases within TCM and offering useful information that will guide future research on TCM.

The Characteristics of TCM Clinical Trials: A Systematic Review of ClinicalTrials.gov

PubMed Central

Huang, Jihan; Li, Jordan V.; Lv, Yinghua; He, Yingchun

2017-01-01

Objective The aim of this review is to characterize current status of global TCM clinical trials registered in ClinicalTrials.gov. Methods We examined all the trials registered within ClinicalTrials.gov up to 25 September 2015, focusing on study interventions to identify TCM-related trials, and extracted 1,270 TCM trials from the data set. Results Overall, 691 (54.4%) trials were acupuncture, and 454 (35.8%) trials were herbal medicines. Differences in TCM trial intervention types were also evident among the specific therapeutic areas. Among all trials, 55.7% that were small studies enrolled <100 subjects, and only 8.7% of completed studies had reported results of trials. As for the location, the United States was second to China in conducting the most TCM trials. Conclusion This review is the first snapshot of the landscape of TCM clinical trials registered in ClinicalTrials.gov, providing the basis for treatment and prevention of diseases within TCM and offering useful information that will guide future research on TCM. PMID:29138646

Ventriculoperitoneal shunt insertion for hydrocephalus in human immunodeficiency virus-infected adults: a systematic review and meta-analysis protocol.

PubMed

Loan, James J M; Mankahla, Ncedile; Meintjes, Graeme; Fieggen, A Graham

2017-10-16

Hydrocephalus is a recognised complication of human immunodeficiency virus (HIV)-related opportunistic infections. Symptomatic raised cerebrospinal fluid pressure can be treated with ventriculoperitoneal shunt insertion (VPS). In HIV-infected patients however, there is a concern that VPS might be associated with unacceptably high rates of mortality. We aim to systematically review and appraise published literature to determine reported outcomes and identify predictors of outcome following VPS in relevant subgroups of HIV-infected adults. The following electronic databases will be searched: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), EMBASE, CINAHL (EBSCOhost), LILACS (BIREME), Research Registry ( www.researchregistry.com ), the metaRegister of Controlled Trials (mRCT) ( www.controlled-trials.com ), ClinicalTrials.gov ( www.clinicaltrials.gov ) and OpenSIGLE database. Any randomised studies, cohort studies, case-control studies, interrupted time series or sequential case series reporting survival following VPS in HIV-infected individuals will be included. If high-quality homogenous studies exist, meta-analysis will be conducted to determine 1-, 6- and 12-month mortality with comparison made between underlying aetiologies of hydrocephalus. This study will generate a comprehensive review of VPS in HIV-infected patients for publication. The primary outcome of meta-analysis is 12-month survival. If only low-quality, heterogeneous studies are available, this study will demonstrate this deficiency and will be of value in justifying and aiding the design of future studies. PROSPERO CRD42016052239.

Positioning and spinal bracing for pain relief in metastatic spinal cord compression in adults.

PubMed

Lee, Siew Hwa; Grant, Robin; Kennedy, Catriona; Kilbride, Lynn

2015-09-24

This is an updated version of the original Cochrane review published in Issue 3 (Lee 2012) on patient positioning (mobilisation) and bracing for pain relief and spinal stability in adults with metastatic spinal cord compression.Many patients with metastatic spinal cord compression (MSCC) have spinal instability, but their clinician has determined that due to their advanced disease they are unsuitable for surgical internal fixation. Mobilising may be hazardous in the presence of spinal instability as further vertebral collapse can occur. Current guidance on positioning (whether a patient should be managed with bed rest or allowed to mobilise) and whether spinal bracing is helpful, is contradictory. To investigate the correct positioning and examine the effects of spinal bracing to relieve pain or to prevent further vertebral collapse in patients with MSCC. For this update, we searched for relevant studies from February 2012 to 31 March 2015. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and MEDLINE In Process, EMBASE, AMED, CINAHL, TRIP, SIGN, NICE, UK Clinical Research Network, National Guideline Clearinghouse and PEDro database. We also searched the metaRegister of Controlled Trials (mRCT), ClinicalTrials.gov, UK Clinical Trials Gateway (UKCTG), WHO International Clinical Trials Registry Platform (ICTRP) and Australia New Zealand Clinical Trials Registry (ANZCTR).For the original version, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, CANCERLIT, NICE, SIGN, AMED, TRIP, National Guideline Clearinghouse, and PEDro database, in February 2012. We selected randomised controlled trials (RCTs) of adults with MSCC of interventions on positioning (mobilisation) and bracing. Two review authors independently assessed each possible study for inclusion and quality. For the original version of the review, we screened 1611 potentially relevant studies. No studies met the inclusion criteria. Many papers identified the importance of mobilisation, but no RCTs of bed rest versus mobilisation have been undertaken. We identified no RCTs of bracing in MSCC.For this update, we identified 347 potential titles. We screened 300 titles and abstracts after removal of duplicates. We did not identify any additional studies for inclusion. Since publication of the original version of this review, no new studies were found and our conclusions remain unchanged.There is a lack of evidence-based guidance around how to correctly position and when to mobilise patients with MSCC or if spinal bracing is an effective technique for reducing pain or improving quality of life. RCTs are required in this important area.

Nonsteroidal anti-inflammatory drugs for dysmenorrhoea.

PubMed

Marjoribanks, Jane; Proctor, Michelle; Farquhar, Cindy; Derks, Roos S

2010-01-20

Dysmenorrhoea is a common gynaecological problem consisting of painful cramps accompanying menstruation, which in the absence of any underlying abnormality is known as primary dysmenorrhoea. Research has shown that women with dysmenorrhoea have high levels of prostaglandins, hormones known to cause cramping abdominal pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs which act by blocking prostaglandin production. The purpose of this review is to compare nonsteroidal anti-inflammatory drugs used in the treatment of primary dysmenorrhoea versus placebo, versus paracetamol and versus each other, to evaluate their effectiveness and safety. We searched the following databases to May 2009: Cochrane Menstrual Disorders and Subfertility Group trials register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Web of Science. The National Research Register and the Clinical Trials Register were also searched. Abstracts of major scientific meetings and the reference lists of relevant articles were checked. All randomised controlled comparisons of NSAIDs versus placebo, other NSAIDs or paracetamol, when used to treat primary dysmenorrhoea. Two reviewers independently assessed trials for quality and extracted data, calculating odds ratios (ORs) for dichotomous outcomes and mean differences for continuous outcomes, with 95% confidence intervals (CIs). Inverse variance methods were used to combine data. Seventy-three randomised controlled trials were included. Among women with primary dysmenorrhoea, NSAIDs were significantly more effective for pain relief than placebo (OR 4.50, 95% CI: 3.85, 5.27). There was substantial heterogeneity for this finding (I(2) statistic =53%): exclusion of two outlying studies with no or negligible placebo effect reduced heterogeneity, resulting in an odds ratio of 4.14 (95% CI: 3.52, 4.86, I(2)=40%). NSAIDs were also significantly more effective for pain relief than paracetamol (OR 1.90, 95% CI:1.05 to 3.44). However, NSAIDS were associated with significantly more overall adverse effects than placebo (OR 1.37, 95% CI: 1.12 to 1.66). When NSAIDs were compared with each other there was little evidence of the superiority of any individual NSAID for either pain-relief or safety. However the available evidence had little power to detect such differences, as most individual comparisons were based on very few small trials. NSAIDs are an effective treatment for dysmenorrhoea, though women using them need to be aware of the significant risk of adverse effects. There is insufficient evidence to determine which (if any) individual NSAID is the safest and most effective for the treatment of dysmenorrhoea.

Surgery for cervical intraepithelial neoplasia

PubMed Central

Martin-Hirsch, Pierre PL; Paraskevaidis, Evangelos; Bryant, Andrew; Dickinson, Heather O; Keep, Sarah L

2014-01-01

Background Cervical intraepithelial neoplasia (CIN) is the most common pre-malignant lesion. Atypical squamous changes occur in the transformation zone of the cervix with mild, moderate or severe changes described by their depth (CIN 1, 2 or 3). Cervical intraepithelial neoplasia is treated by local ablation or lower morbidity excision techniques. Choice of treatment depends on the grade and extent of the disease. Objectives To assess the effectiveness and safety of alternative surgical treatments for CIN. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE and EMBASE (up to April 2009). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria Randomised controlled trials (RCTs) of alternative surgical treatments in women with cervical intraepithelial neoplasia. Data collection and analysis Two review authors independently abstracted data and assessed risks of bias. Risk ratios that compared residual disease after the follow-up examination and adverse events in women who received one of either laser ablation, laser conisation, large loop excision of the transformation zone (LLETZ), knife conisation or cryotherapy were pooled in random-effects model meta-analyses. Main results Twenty-nine trials were included. Seven surgical techniques were tested in various comparisons. No significant differences in treatment failures were demonstrated in terms of persistent disease after treatment. Large loop excision of the transformation zone appeared to provide the most reliable specimens for histology with the least morbidity. Morbidity was lower than with laser conisation, although the trials did not provide data for every outcome measure. There were not enough data to assess the effect on morbidity when compared with laser ablation. Authors’ conclusions The evidence suggests that there is no obvious superior surgical technique for treating cervical intraepithelial neoplasia in terms of treatment failures or operative morbidity. PMID:20556751

Efficacy of mummy on healing of pressure ulcers: A randomized controlled clinical trial on hospitalized patients in intensive care unit

PubMed Central

Moghadari, Masoud; Rezvanipour, Mozafar; Mehrabani, Mitra; Ahmadinejad, Mehdi; Hashempur, Mohammad Hashem

2018-01-01

Background Mummy is a mineral substance which according to Persian medicine texts, may be useful in treatment of chronic ulcers. Objective The present study was performed with the aim of determining the effect of mummy on healing of pressure in male patients who had been hospitalized due to cerebrospinal injury in the Intensive Care Unit. Methods This randomized, placebo-controlled clinical trial was performed on 75 patients who had pressure ulcer at Shahid Bahonar Hospital in Kerman, Iran, from September 2016 to March 2017. The control group received normal saline and routine wound dressing, while the intervention group received mummy water solution 20% in addition to normal saline and routine wound dressing on a daily basis. Data was recorded based on the PUSH method. In both groups, ulcers were evaluated on days 0, 7, 14, 21 and 28 for the variables of ulcer surface area, the amount of exudate and type of tissue. Data analysis was done through SPSS 21 and using t-test, Repeated Measure Analysis, Cox Regression and Chi-square. Results Both groups showed reduction in the average ulcer surface area (3.26 to 0.53 in the intervention group and 5.1 to 3.46 in the control group), the average exudate amount (1.26 to 0.26 in the intervention group and 1.83 to 1.06 in the control group) and the average tissue score (1.36 to 0.23 in the intervention group and 2.13 to 1.26 in the control group). Over the entire study period, the intervention group showed more acceptable signs of healing compared to the control group (p<0.05). Conclusion The healing process was more prominent in the intervention group than the control group. Clinical trial registration The trial was registered at the Iranian Registry of Clinical Trials with registered NO. (IRCT2014042917494N1) (29/04/2014). Funding No financial support for the research. PMID:29588812

78 FR 5497 - Importer of Controlled Substances; Notice of Registration; Fisher Clinical Services, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

... Registration; Fisher Clinical Services, Inc. By Notice dated November 1, 2012, and published in the Federal Register on November 9, 2012, 77 FR 67396, Fisher Clinical Services, Inc., 7554 Schantz Road, Allentown... plans to import the listed controlled substance to conduct clinical trials. No comments or objections...

A Cluster Randomised Trial Introducing Rapid Diagnostic Tests into Registered Drug Shops in Uganda: Impact on Appropriate Treatment of Malaria

PubMed Central

Mbonye, Anthony K.; Magnussen, Pascal; Lal, Sham; Hansen, Kristian S.; Cundill, Bonnie; Chandler, Clare; Clarke, Siân E.

2015-01-01

Background Inappropriate treatment of malaria is widely reported particularly in areas where there is poor access to health facilities and self-treatment of fevers with anti-malarial drugs bought in shops is the most common form of care-seeking. The main objective of the study was to examine the impact of introducing rapid diagnostic tests for malaria (mRDTs) in registered drug shops in Uganda, with the aim to increase appropriate treatment of malaria with artemisinin-based combination therapy (ACT) in patients seeking treatment for fever in drug shops. Methods A cluster-randomized trial of introducing mRDTs in registered drug shops was implemented in 20 geographical clusters of drug shops in Mukono district, central Uganda. Ten clusters were randomly allocated to the intervention (diagnostic confirmation of malaria by mRDT followed by ACT) and ten clusters to the control arm (presumptive treatment of fevers with ACT). Treatment decisions by providers were validated by microscopy on a reference blood slide collected at the time of consultation. The primary outcome was the proportion of febrile patients receiving appropriate treatment with ACT defined as: malaria patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving ACT or rectal artesunate, and patients with no malaria parasites not given ACT. Findings A total of 15,517 eligible patients (8672 intervention and 6845 control) received treatment for fever between January-December 2011. The proportion of febrile patients who received appropriate ACT treatment was 72·9% versus 33·7% in the control arm; a difference of 36·1% (95% CI: 21·3 – 50·9), p<0·001. The majority of patients with fever in the intervention arm accepted to purchase an mRDT (97·8%), of whom 58·5% tested mRDT-positive. Drug shop vendors adhered to the mRDT results, reducing over-treatment of malaria by 72·6% (95% CI: 46·7– 98·4), p<0·001) compared to drug shop vendors using presumptive diagnosis (control arm). Conclusion Diagnostic testing with mRDTs compared to presumptive treatment of fevers implemented in registered drug shops substantially improved appropriate treatment of malaria with ACT. Trial Registration ClinicalTrials.gov NCT01194557. PMID:26200467

Volunteer Bias in Recruitment, Retention, and Blood Sample Donation in a Randomised Controlled Trial Involving Mothers and Their Children at Six Months and Two Years: A Longitudinal Analysis

PubMed Central

Jordan, Sue; Watkins, Alan; Storey, Mel; Allen, Steven J.; Brooks, Caroline J.; Garaiova, Iveta; Heaven, Martin L.; Jones, Ruth; Plummer, Sue F.; Russell, Ian T.; Thornton, Catherine A.; Morgan, Gareth

2013-01-01

Background The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not. Methods and Results This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i)As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13–0.67 and 0.20,0.09–0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50–0.93 and 0.55,0.28–1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57–0.92 and 0.43,0.22–0.83). ii)Mothers interested in probiotics or research or reporting infants’ adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9–13.1%) to 4.6%(−1.4–+10.5%), and OR from 0.40(0.18–0.91) to 0.56(0.26–1.21). Other findings were unchanged. Conclusions Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome. Trial Registration This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children. PMID:23874465

Propofol versus thiopental sodium for the treatment of refractory status epilepticus (Review).

PubMed

Prabhakar, Hemanshu; Bindra, Ashish; Singh, Gyaninder Pal; Kalaivani, Mani

2013-07-01

Failure to respond to antiepileptic drugs in uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (10 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library 2012), and MEDLINE (1946 to May week 1, 2012). We also searched (10 May 2012) ClinicalTrials.gov, The South Asian Database of Controlled Clinical Trials, and IndMED (a bibliographic database of Indian Medical Journals). All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol. Two review authors screened the search results and reviewed abstracts of relevant and eligible trials before retrieving the full text publications. One study was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE and receiving either propofol or thiopental sodium for the control of seizure activity (Rossetti 2011). This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. There was no evidence of a difference between the drugs with respect to the outcome measures such as control of seizure activity and functional outcome at three months. There is lack of robust and randomised controlled evidence that can clarify the efficacy of propofol and thiopental sodium over each other in the treatment of RSE. There is a need for large, randomised controlled trials for this serious condition. Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Chinese herbal medicine for diabetic peripheral neuropathy.

PubMed

Chen, Wei; Zhang, Yin; Liu, Jian Ping

2011-06-15

Chinese herbal medicine is frequently used for treating diabetic peripheral neuropathy in China. Many controlled trials have been undertaken to investigate its efficacy. To assess the beneficial effects and harms of Chinese herbal medicine for people with diabetic peripheral neuropathy. We searched the Cochrane Neuromuscular Disease Group Specialized Register (15 June 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2010 in The Cochrane Library), MEDLINE (January 1966 to June 2010), EMBASE (January 1980 to June 2010), AMED (January 1985 to June 2010), Chinese Biomedical Database (CBM) (1979 to June 2010), Chinese National Knowledge Infrastructure Database (CNKI) (1979 to June 2010), and VIP Chinese Science and Technique Journals Database (1989 to June 2010). We searched for unpublished literature in the Chinese Conference Papers Database and Chinese Dissertation Database (from inception to March 2010). No language or publication restrictions were used. We included randomized controlled trials of Chinese herbal medicine (with a minimum of four weeks treatment duration) for people with diabetic peripheral neuropathy compared with placebo, no intervention, or conventional interventions. Trials of herbal medicine plus a conventional drug versus the drug alone were also included. Two authors independently extracted data and evaluated trial quality. We contacted study authors for additional information. The data analyses were carried out using Review Manager 5.1 (Cochrane software). Thirty-nine randomized trials involving 2890 participants were included. All trials were conducted and published in China. Thirty different herbal medicines were tested in these trials, including four single herbs (extracts from a single herb), eight traditional Chinese patent medicines, and 18 self-concocted Chinese herbal compound prescriptions. The trials reported on global symptom improvement (including improvement in numbness or pain) and changes in nerve conduction velocity. There was inadequate reporting on adverse events in the included trials. Most of the trials did not mention whether they monitored adverse effects at all. Only two trials reported adverse events: one occurred in the control group in one trial and in which group was unclear in the other trial . Conclusions cannot be drawn from this review about the safety of herbal medicines due to inadequate reporting. Most of the trials were of low methodological quality and therefore the interpretation of any positive findings for the efficacy of the included Chinese herbal medicines for treating diabetic peripheral neuropathy should be made with caution. Based on this systematic review, there is no evidence to support the objective effectiveness and safety of Chinese herbal medicines for diabetic peripheral neuropathy. No well designed, randomized placebo controlled trial with objective outcome measures has been conducted.

The quality of registration of clinical trials.

PubMed

Viergever, Roderik F; Ghersi, Davina

2011-02-24

Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials. A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame. Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records.

The Quality of Registration of Clinical Trials

PubMed Central

Viergever, Roderik F.; Ghersi, Davina

2011-01-01

Background Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials. Methods and Findings A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame. Conclusions Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records. PMID:21383991

Strengthening the reliability and credibility of observational epidemiology studies by creating an Observational Studies Register.

PubMed

Swaen, Gerard M H; Carmichael, Neil; Doe, John

2011-05-01

To evaluate the need for the creation of a system in which observational epidemiology studies are registered; an Observational Studies Register (OSR). The current scientific process for observational epidemiology studies is described. Next, a parallel is made with the clinical trials area, where the creation of clinical trial registers has greatly restored and improved their credibility and reliability. Next, the advantages and disadvantages of an OSR are compared. The advantages of an OSR outweigh its disadvantages. The creation of an OSR, similar to the existing Clinical Trials Registers, will improve the assessment of publication bias and will provide an opportunity to compare the original study protocol with the results reported in the publication. Reliability, credibility, and transparency of observational epidemiology studies are strengthened by the creation of an OSR. We propose a structured, collaborative, and coordinated approach for observational epidemiology studies that can provide solutions for existing weaknesses and will strengthen credibility and reliability, similar to the approach currently used in clinical trials, where Clinical Trials Registers have played a key role in strengthening their scientific value. Copyright © 2011 Elsevier Inc. All rights reserved.

Perioperative enhanced recovery programmes for gynaecological cancer patients.

PubMed

Lv, Donghao; Wang, Xuan; Shi, Gang

2010-06-16

Gynaecological malignancies contribute to 10 to 15% of cancers in women internationally. In recent years, a trend towards new perioperative care strategies has been documented as "Fast Track (FT) surgery", or "Enhanced Recovery Programmes" to replace some traditional approaches in surgical care. The FT multimodal programmes may enhance the postoperative recovery by means of reducing surgical stress. This systematic review aims to fully assess the beneficial and harmful effects of FT programmes in gynaecological cancer care. To evaluate the beneficial and harmful effects of FT programmes in gynaecological cancer care. We searched the following databases, The Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 4, 2009, MEDLINE and EMBASE to November 2009. In addition, all reference lists of included trials were searched and experts in the gynaecological oncology community were contacted in an attempt to locate trials. All randomised controlled trials (RCTs) comparing any type of FT programmes for surgery in gynaecological cancer to conventional recovery strategies were included. Two review authors independently screened studies for inclusion. Since no RCTs were identified, data collection and analysis could not be performed. No studies were found that met the inclusion criteria. We currently have no evidence from high quality studies to support or refute the use of perioperative enhanced recovery programmes for gynaecological cancer patients. Further well-designed RCTs with standard FT programmes are needed.

Acupuncture for Bell's palsy.

PubMed

Chen, Ning; Zhou, Muke; He, Li; Zhou, Dong; Li, N

2010-08-04

Bell's palsy or idiopathic facial palsy is an acute facial paralysis due to inflammation of the facial nerve. A number of studies published in China have suggested acupuncture is beneficial for facial palsy. The objective of this review was to examine the efficacy of acupuncture in hastening recovery and reducing long-term morbidity from Bell's palsy. We updated the searches of the Cochrane Neuromuscular Disease Group Trials Specialized Register (24 May 2010), The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2010), MEDLINE (January 1966 to May 2010), EMBASE (January 1980 to May 2010), AMED (January 1985 to May 2010), LILACS (from January 1982 to May 2010) and the Chinese Biomedical Retrieval System (January 1978 to May 2010) for randomised controlled trials using 'Bell's palsy' and its synonyms, 'idiopathic facial paralysis' or 'facial palsy' as well as search terms including 'acupuncture'. Chinese journals in which we thought we might find randomised controlled trials relevant to our study were handsearched. We reviewed the bibliographies of the randomised trials and contacted the authors and known experts in the field to identify additional published or unpublished data. We included all randomised controlled trials involving acupuncture by needle insertion in the treatment of Bell's palsy irrespective of any language restrictions. Two review authors identified potential articles from the literature search, extracted data and assessed quality of each trial independently. All disagreements were resolved by discussion between the review authors. The literature search and handsearching identified 49 potentially relevant articles. Of these, six RCTs were included involving 537 participants with Bell's palsy. Two more possible trials were identified in the update than the previous version of this systematic review, but both were excluded because they were not real RCTs. Of the six included trials, five used acupuncture while the other one used acupuncture combined with drugs. No trial reported on the outcomes specified for this review. Harmful side effects were not reported in any of the trials. Poor quality caused by flaws in study design or reporting (including uncertain method of randomisation, allocation concealment and blinding) and clinical differences between trials prevented reliable conclusions about the efficacy of acupuncture. The quality of the included trials was inadequate to allow any conclusion about the efficacy of acupuncture. More research with high quality trials is needed.

The effects of computer-based mindfulness training on Self-control and Mindfulness within Ambulatorily assessed network Systems across Health-related domains in a healthy student population (SMASH): study protocol for a randomized controlled trial.

PubMed

Rowland, Zarah; Wenzel, Mario; Kubiak, Thomas

2016-12-01

Self-control is an important ability in everyday life, showing associations with health-related outcomes. The aim of the Self-control and Mindfulness within Ambulatorily assessed network Systems across Health-related domains (SMASH) study is twofold: first, the effectiveness of a computer-based mindfulness training will be evaluated in a randomized controlled trial. Second, the SMASH study implements a novel network approach in order to investigate complex temporal interdependencies of self-control networks across several domains. The SMASH study is a two-armed, 6-week, non-blinded randomized controlled trial that combines seven weekly laboratory meetings and 40 days of electronic diary assessments with six prompts per day in a healthy undergraduate student population at the Johannes Gutenberg University Mainz, Germany. Participants will be randomly assigned to (1) receive a computer-based mindfulness intervention or (2) to a wait-list control condition. Primary outcomes are self-reported momentary mindfulness and self-control assessed via electronic diaries. Secondary outcomes are habitual mindfulness and habitual self-control. Further measures include self-reported behaviors in specific self-control domains: emotion regulation, alcohol consumption and eating behaviors. The effects of mindfulness training on primary and secondary outcomes are explored using three-level mixed models. Furthermore, networks will be computed with vector autoregressive mixed models to investigate the dynamics at participant and group level. This study was approved by the local ethics committee (reference code 2015_JGU_psychEK_011) and follows the standards laid down in the Declaration of Helsinki (2013). This randomized controlled trial combines an intensive Ambulatory Assessment of 40 consecutive days and seven laboratory meetings. By implementing a novel network approach, underlying processes of self-control within different health domains will be identified. These results will deepen the understanding of self-control performance and will guide to just-in-time individual interventions for several health-related behaviors. ClinicalTrials.gov, NCT02647801 . Registered on 15 December 2015 (registered retrospectively). .

Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis.

PubMed

Johansen, Helle Krogh; Gøtzsche, Peter C

2015-08-23

Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. This is an update of a previously published review. To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30 March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013). Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis. The authors independently selected trials, assessed them and extracted data. Six trials were identified. Two trials were excluded since they were not randomised and one old, small trial because it was not possible to assess whether is was randomised. The three included trials comprised 483, 476 and 37 patients, respectively. No data have been published from one of the large trials, but the company stated in a press release that the trial failed to confirm the results from an earlier study and that further clinical development was suspended. In the other large trial, relative risk for chronic infection was 0.91 (95% confidence interval 0.55 to 1.49), and in the small trial, the risk was also close to one. In the large trial, one patient was reported to have died in the observation period. In that trial, 227 adverse events (4 severe) were registered in the vaccine group and 91 (1 severe) in the control group. In this large trial of a vaccine developed against flagella antigens, antibody titres against the epitopes contained in the vaccine were higher in the vaccine group compared to the placebo group (P < 0.0001). Vaccines against Pseudomonas aeruginosa cannot be recommended.

The heart of the matter: Outcome reporting bias and registration status in cardio-thoracic surgery.

PubMed

Wiebe, Jordan; Detten, Grant; Scheckel, Caleb; Gearhart, David; Wheeler, Denna; Sanders, Donald; Vassar, Matt

2017-01-15

Our objective is to compare registered outcomes to published reports; to evaluate for discrepancies favoring statistically significant outcomes; to examine funding source and likelihood of outcome reporting bias; and to evaluate for any temporal trends in outcome reporting bias. PubMed was searched for randomized controlled trials published between 2008 and 2015 from 4 high impact cardio-thoracic journals: European Journal of Cardio-thoracic Surgery (EJCS), The Journal of Cardiothoracic Surgery (JCS), The Journal of Thoracic and Cardiovascular Surgery (JTCS), and Annals of Cardiothoracic Surgery (ACS). Data was collected using a standardized extraction form. We reviewed 287 articles, of which 214 (74.6%) did not meet registration criteria. Of those 214, 94 (43.9%) were published in the EJCS, 34 (15.9%) in JCS, 86 (40.2%) in JTCS, and 0 (0%) in the ACS. Of the remaining 73 articles, 34 (46.6%) had a discrepancy between the primary outcome registered and the published outcome, and 11 of the 34 reported p-values favoring the change. We also found that 12 of the 73 registrations had updated primary outcomes from the initial report to the final report. The timing of registration was an incidental finding showing 14 (19.1%) articles retrospectively registered, 29 (39.7%) registered during patient enrollment, and 30 (41.1%) registered prospectively. The results indicated that selective outcome reporting is prevalent in cardio-thoracic surgery journals. The more concerning issue, however, is the lack of registration or provision of registration number for randomized controlled trials within these journals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Volunteer bias in recruitment, retention, and blood sample donation in a randomised controlled trial involving mothers and their children at six months and two years: a longitudinal analysis.

PubMed

Jordan, Sue; Watkins, Alan; Storey, Mel; Allen, Steven J; Brooks, Caroline J; Garaiova, Iveta; Heaven, Martin L; Jones, Ruth; Plummer, Sue F; Russell, Ian T; Thornton, Catherine A; Morgan, Gareth

2013-01-01

The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not. This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i) As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13-0.67 and 0.20,0.09-0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50-0.93 and 0.55,0.28-1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57-0.92 and 0.43,0.22-0.83). ii) Mothers interested in probiotics or research or reporting infants' adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9-13.1%) to 4.6%(-1.4-+10.5%), and OR from 0.40(0.18-0.91) to 0.56(0.26-1.21). Other findings were unchanged. Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome. This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children.

Antidepressants for depressive disorder in children and adolescents: a database of randomised controlled trials.

PubMed

Zhang, Yuqing; Zhou, Xinyu; Pu, Juncai; Zhang, Hanping; Yang, Lining; Liu, Lanxiang; Zhou, Chanjuan; Yuan, Shuai; Jiang, Xiaofeng; Xie, Peng

2018-05-31

In recent years, whether, when and how to use antidepressants to treat depressive disorder in children and adolescents has been hotly debated. Relevant evidence on this topic has increased rapidly. In this paper, we present the construction and content of a database of randomised controlled trials of antidepressants to treat depressive disorder in children and adolescents. This database can be freely accessed via our website and will be regularly updated. Major bibliographic databases (PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO and LiLACS), international trial registers and regulatory agencies' websites were systematically searched for published and unpublished studies up to April 30, 2017. We included randomised controlled trials in which the efficacy or tolerability of any oral antidepressant was compared with that of a control group or any other treatment. In total, 7377 citations from bibliographical databases and 3289 from international trial registers and regulatory agencies' websites were identified. Of these, 53 trials were eligible for inclusion in the final database. Selected data were extracted from each study, including characteristics of the participants (the study population, setting, diagnostic criteria, type of depression, age, sex, and comorbidity), characteristics of the treatment conditions (the treatment conditions, general information, and detail of pharmacotherapy and psychotherapy) and study characteristics (the sponsor, country, number of sites, blinding method, sample size, treatment duration, depression scales, other scales, and primary outcome measure used, and side-effect monitoring method). Moreover, the risk of bias for each trial were assessed. This database provides information on nearly all randomised controlled trials of antidepressants in children and adolescents. By using this database, researchers can improve research efficiency, avoid inadvertent errors and easily focus on the targeted subgroups in which they are interested. For authors of subsequent reviews, they could only use this database to insure that they have completed a comprehensive review, rather than relied solely on the data from this database. We expect this database could help to promote research on evidence-based practice in the treatment of depressive disorder in children and adolescents. The database could be freely accessed in our website: http://xiepengteam.cn/research/evidence-based-medicine .

The effect of vitamin B12 supplementation in Nepalese infants on growth and development: study protocol for a randomized controlled trial.

PubMed

Strand, Tor A; Ulak, Manjeswori; Chandyo, Ram K; Kvestad, Ingrid; Hysing, Mari; Shrestha, Merina; Basnet, Sudha; Ranjitkar, Suman; Shrestha, Laxman; Shrestha, Prakash S

2017-04-21

Vitamin B 12 deficiency is one of the most common micronutrient deficiencies and is associated with poor cognitive development and growth. Vitamin B 12 is crucial for normal cell division and differentiation, and it is necessary for the development and myelination of the central nervous system. The aim of the present study is to measure the effect of daily supplementation of vitamin B 12 on the neurodevelopment and growth of young children in Nepal. We are conducting an individually randomized, double-blind, placebo-controlled trial with 600 marginally stunted children 6-11 months old (length for age less than -1 z-score). Children are randomized to receive a lipid-based paste containing vitamin B 12 or placebo daily for 12 months. The main outcomes are changes in growth (z-scores) and in neurodevelopment measured by the Bayley Scales of Infant and Toddler Development, Third Edition, from baseline until the end of the study. If vitamin B 12 supplementation benefits early child development and growth, this will have consequences for dietary recommendations for malnourished children worldwide. ClinicalTrials.gov Identifier: NCT02272842 . Registered on 21 October 2014. Universal Trial Number: U1111-1161-5187. Registered on 8 September 2014.

Environmental sanitary interventions for preventing active trachoma.

PubMed

Rabiu, M; Alhassan, M; Ejere, H

2005-04-18

Trachoma is the second or third major cause of blindness. It is responsible for about six million blind people worldwide, mostly in the poor communities of developing countries. One of the major strategies advocated for the control of the disease is the application of various environmental sanitary measures to such communities. To assess the evidence for the effectiveness of environmental sanitary measures on the prevalence of active trachoma in endemic areas. We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (Issue 4, 2004), MEDLINE (1966 to January 2005), EMBASE (1980 to January 2005), LILACS (April 2004), the reference list of trials and the Science Citation Index. We also contacted agencies, experts and researchers in trachoma control. This review included randomised and quasi-randomised controlled trials comparing any form of environmental hygiene measures with no measure. These hygienic measures included fly control, provision of water and health education. Participants in the trials were people normally resident in the trachoma endemic areas. Two authors independently extracted data and assessed the quality of trials. Study authors were contacted for additional information. Three trials met the inclusion criteria but meta-analysis was not conducted due to heterogeneity of the studies. Two studies that assessed insecticide spray as a fly control measure found that trachoma is reduced by at least 55% to 61% with this measure compared to no intervention. One study found that another fly control measure, latrine provision, reduced trachoma by 29.5% compared to no intervention; this was, however, not statistically significantly different. Another study revealed that health education on personal and household hygiene reduced the incidence of trachoma such that the odds of reducing trachoma in the health education village was about twice that of the no intervention village. However, all the studies have some methodological concerns relating to concealment of allocation and non-consideration of clustering effect in data analysis. There is evidence that insecticide spray as a fly control measure reduces trachoma significantly. Latrine provision as a fly control measure has not demonstrated significant trachoma reduction. Health education may be effective in reducing trachoma. There is a dearth of data to determine the effectiveness of all aspects of environmental sanitation in the control of trachoma.

Exit interviews to reduce turnover amongst healthcare professionals.

PubMed

Webster, Joan; Flint, Anndrea

2014-08-19

Exit interviews are widely used in healthcare organisations to identify reasons for staff attrition, yet their usefulness in limiting turnover is unclear. To determine the effectiveness of various exit interview strategies in decreasing turnover rates amongst healthcare professionals. We searched the Cochrane EPOC Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL), Issue 11, 2012; MEDLINE, Ovid (1950- ); EMBASE, Ovid (1947- ); CINAHL, EbscoHost (1980- ), and PsycINFO, OVID (1806-) between October 31 and November 6, 2012. We also screened the reference lists of included studies and relevant reviews; and searched trial registries for planned and on-going studies. We did not restrict searches by language or publication date. Randomised controlled trials, controlled clinical trials, controlled before-after studies and interrupted time series studies comparing turnover rates between healthcare professionals who had undergone one form of exit interview with another form of exit interview or with no interview. Two review authors independently assessed trial quality and extracted data. The original search identified 1560 citations, of which we considered 19 potentially relevant. The two authors independently reviewed the abstracts of these studies and retrieved the full texts of eight studies. We excluded all eight following independent assessment; they were either interviews, commentaries on how to do an exit interview or descriptive studies about reasons for leaving. We found no studies that matched our inclusion criteria. For this first update, we screened 2220 citations and identified no new studies. Evidence about the effectiveness of exit interviews to reduce turnover is currently not available. However, exit interviews may provide useful information about the work environment which, in turn, may be useful in the development of interventions to reduce turnover.

Acute and chronic effects of aerobic exercise on blood pressure in resistant hypertension: study protocol for a randomized controlled trial.

PubMed

Nascimento, L S; Santos, A C; Lucena, Jms; Silva, Lgo; Almeida, Aem; Brasileiro-Santos, M S

2017-06-02

Resistant hypertension is a specific condition that affects approximately 10% of subjects with hypertension, and is characterized by persistently high blood pressure levels even using therapy of three or more antihypertensive agents or with blood pressure control using therapy with four or more antihypertensive agents. Changes in lifestyle, such as physical exercise, are indicated for controlling blood pressure. However, investigating studies about this therapy in individuals with resistant hypertension are few. This is a randomized controlled clinical trial. Forty-eight patients with resistant hypertension will be submitted to perform four short-term interventions: aerobic exercise sessions (mild-, moderate- and high-intensity) and control session, in random order and on separate days. After the short-term sessions, the patients will be randomly allocated into four groups for 8 weeks of follow-up: mild-, moderate- and high-intensity aerobic exercise, and a control group. The primary outcome is the occurrence of blood pressure reduction (office and ambulatory analysis, and acute and chronic effects). Secondary outcomes are autonomic and hemodynamic mechanisms: cardiac and vasomotor autonomic modulation, spontaneous baroreflex sensitivity, forearm blood flow and vascular resistance. The importance of exercise for hypertension has been known for decades, but little is known about the effects on patients with resistant hypertension. This study will help to understand whether different aerobic exercise intensities can induce different responses, as well as by what mechanisms adjustments in blood pressure levels may occur. ClinicalTrials.gov, ID: NCT02670681 . Registered on 28 January 2016 (first version); Brazilian Registry Platform Clinical Trials: protocol RBR-5q24zh . Registered on 24 June 2015.

Characteristics and trends of clinical trials funded by the National Institutes of Health between 2005 and 2015.

PubMed

Gresham, Gillian K; Ehrhardt, Stephan; Meinert, Jill L; Appel, Lawrence J; Meinert, Curtis L

2018-02-01

Background The National Institutes of Health is one of the largest biomedical research agencies in the world. Clinical trials are an important component of National Institutes of Health research efforts. Given the recent updates in National Institutes of Health trial reporting requirements, more information regarding the current state of National Institutes of Health-funded clinical trials is warranted. The objective of this analysis was to describe characteristics and trends of clinical trials funded by the National Institutes of Health over time and by Institutes and Centers of the National Institutes of Health. Methods Interventional studies funded by the National Institutes of Health and registered in ClinicalTrials.gov between 2005 and 2015 were included in the analysis. Trials were identified from the 27 March 2016 Clinical Trials Transformation Initiative Aggregate Analysis of ClinicalTrials.gov database. A descriptive analysis of trials by year and National Institutes of Health Institute/Center was performed. Results There were 12,987 National Institutes of Health-funded clinical trials registered between 2005 and 2015. There were 1,580, 1,116, and 930 trials registered in 2005, 2010, and 2015, respectively. The majority were early-development trials (phases 0, 1, or 2; 53%), randomized (61%), and single-center (63%). Trial demographics have remained unchanged over time. Median trial sample size was 64 (interquartile range 29-192) with 10% of trials enrolling ≥500 participants. Most trials were completed within 5 years of enrollment start (69%). Trial characteristics varied considerably across National Institutes of Health Institutes and Centers. Results were reported under the assumptions that most National Institutes of Health-funded trials are registered in ClinicalTrials.gov and that trials are being registered completely and accurately. Conclusion In conclusion, there has been a decline in the number of trials being funded over time, explained in part by a relatively constant budget, increases in trial costs, or other factors that cannot be quantified. National Institutes of Health-funded trials are relatively small and tend to be single-centered. There are substantial differences in the number and types of trials done by Institutes and Centers within the National Institutes of Health.

A modified Mediterranean dietary intervention for adults with major depression: Dietary protocol and feasibility data from the SMILES trial.

PubMed

Opie, Rachelle S; O'Neil, Adrienne; Jacka, Felice N; Pizzinga, Josephine; Itsiopoulos, Catherine

2017-04-19

The SMILES trial was the first randomized controlled trial (RCT) explicitly designed to evaluate a dietary intervention, conducted by qualified dietitians, for reducing depressive symptomatology in adults with clinical depression. Here we detail the development of the prescribed diet (modified Mediterranean diet (ModiMedDiet)) for individuals with major depressive disorders (MDDs) that was designed specifically for the SMILES trial. We also present data demonstrating the extent to which this intervention achieved improvements in diet quality. The ModiMedDiet was designed using a combination of existing dietary guidelines and scientific evidence from the emerging field of nutritional psychiatric epidemiology. Sixty-seven community dwelling individuals (Melbourne, Australia) aged 18 years or over, with current poor quality diets, and MDDs were enrolled into the SMILES trial. A retention rate of 93.9 and 73.5% was observed for the dietary intervention and social support control group, respectively. The dietary intervention (ModiMedDiet) consisted of seven individual nutrition counselling sessions delivered by a qualified dietitian. The control condition comprised a social support protocol matched to the same visit schedule and length. This manuscript details the first prescriptive individualized dietary intervention delivered by dietitians for adults with major depression. Significant improvements in dietary quality were observed among individuals randomized to the ModiMedDiet group. These dietary improvements were also found to be associated with changes in depressive symptoms. The ModiMedDiet, a novel and individually tailored intervention designed specifically for adults with major depression, can be effectively implemented in clinical practice to manage this highly prevalent and debilitating condition. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820. Registered 29 February 2012.

First-in-man mesenchymal stem cells for radiation-induced xerostomia (MESRIX): study protocol for a randomized controlled trial.

PubMed

Grønhøj, Christian; Jensen, David H; Glovinski, Peter V; Jensen, Siri Beier; Bardow, Allan; Oliveri, Roberto S; Specht, Lena; Thomsen, Carsten; Darkner, Sune; Kiss, Katalin; Fischer-Nielsen, Anne; von Buchwald, Christian

2017-03-07

Salivary gland hypofunction and xerostomia are major complications following radiotherapy for head and neck cancer and may lead to debilitating oral disorders and impaired quality of life. Currently, only symptomatic treatment is available. However, mesenchymal stem cell (MSC) therapy has shown promising results in preclinical studies. Objectives are to assess safety and efficacy in a first-in-man trial on adipose-derived MSC therapy (ASC) for radiation-induced xerostomia. This is a single-center, phase I/II, randomized, placebo-controlled, double-blinded clinical trial. A total of 30 patients are randomized in a 1:1 ratio to receive ultrasound-guided, administered ASC or placebo to the submandibular glands. The primary outcome is change in unstimulated whole salivary flow rate. The secondary outcomes are safety, efficacy, change in quality of life, qualitative and quantitative measurements of saliva, as well as submandibular gland size, vascularization, fibrosis, and secretory tissue evaluation based on contrast-induced magnetic resonance imaging (MRI) and core-needle samples. The assessments are performed at baseline (1 month prior to treatment) and 1 and 4 months following investigational intervention. The trial is the first attempt to evaluate the safety and efficacy of adipose-derived MSCs (ASCs) in patients with radiation-induced xerostomia. The results may provide evidence for the effectiveness of ASC in patients with salivary gland hypofunction and xerostomia and deliver valuable information for the design of subsequent trials. EudraCT, Identifier: 2014-004349-29. Registered on 1 April 2015. ClinicalTrials.gov, Identifier: NCT02513238 . First received on 2 July 2015. The trial is prospectively registered.

A multicenter, randomized controlled trial comparing the identification rate of stigmata of recent hemorrhage and rebleeding rate between early and elective colonoscopy in outpatient-onset acute lower gastrointestinal bleeding: study protocol for a randomized controlled trial.

PubMed

Niikura, Ryota; Nagata, Naoyoshi; Yamada, Atsuo; Doyama, Hisashi; Shiratori, Yasutoshi; Nishida, Tsutomu; Kiyotoki, Shu; Yada, Tomoyuki; Fujita, Tomoki; Sumiyoshi, Tetsuya; Hasatani, Kenkei; Mikami, Tatsuya; Honda, Tetsuro; Mabe, Katsuhiro; Hara, Kazuo; Yamamoto, Katsumi; Takeda, Mariko; Takata, Munenori; Tanaka, Mototsugu; Shinozaki, Tomohiro; Fujishiro, Mitsuhiro; Koike, Kazuhiko

2018-04-03

The clinical benefit of early colonoscopy within 24 h of arrival in patients with severe acute lower gastrointestinal bleeding (ALGIB) remains controversial. This trial will compare early colonoscopy (performed within 24 h) versus elective colonoscopy (performed between 24 and 96 h) to examine the identification rate of stigmata of recent hemorrhage (SRH) in ALGIB patients. We hypothesize that, compared with elective colonoscopy, early colonoscopy increases the identification of SRH and subsequently improves clinical outcomes. This trial is an investigator-initiated, multicenter, randomized, open-label, parallel-group trial examining the superiority of early colonoscopy over elective colonoscopy (standard therapy) in ALGIB patients. The primary outcome measure is the identification of SRH. Secondary outcomes include 30-day rebleeding, success of endoscopic treatment, need for additional endoscopic examination, need for interventional radiology, need for surgery, need for transfusion during hospitalization, length of stay, 30-day thrombotic events, 30-day mortality, preparation-related adverse events, and colonoscopy-related adverse events. The sample size will enable detection of a 9% SRH rate in elective colonoscopy patients and a SRH rate of ≥ 26% in early colonoscopy patients with a risk of type I error of 5% and a power of 80%. This trial will provide high-quality data on the benefits and risks of early colonoscopy in ALGIB patients. UMIN-CTR Identifier, UMIN000021129 . Registered on 21 February 2016; ClinicalTrials.gov Identifier, NCT03098173 . Registered on 24 March 2017.

Botulinum toxin for upper oesophageal sphincter dysfunction in neurological swallowing disorders.

PubMed

Regan, Julie; Murphy, Anne; Chiang, Mindy; McMahon, Barry P; Coughlan, Tara; Walshe, Margaret

2014-05-06

Adequate upper oesophageal sphincter (UOS) opening is critical to safe and efficient swallowing due to the close proximity of the UOS to the airway entrance. Many people with neurological conditions, progressive and non-progressive, present with UOS dysfunction. The consequences for the person include difficulty swallowing food with subsequent choking and aspiration (passage of material into the trachea beyond the level of the true vocal cords). Clinical complications include aspiration pneumonia, weight loss, dehydration and malnutrition. Tube feeding is often indicated but is associated with increased mortality. Quality of life is also frequently impacted. A range of interventions exist that aim to improve UOS function and swallowing. These include compensatory strategies, rehabilitation techniques, pharmacological interventions and surgery. Over the last two decades, botulinum toxin has been gaining popularity as an intervention for UOS dysfunction, with some evidence to suggest that it is successful in improving swallow function. Despite a number of studies investigating its efficacy, there is a lack of consensus regarding whether this intervention is effective in improving swallowing for individuals with UOS dysfunction associated with neurological disease. To establish the efficacy and safety of botulinum toxin use aimed at improving UOS dysfunction in people with swallowing difficulties (dysphagia) associated with non-progressive and progressive neurological disease. We searched the following electronic databases for published trials: the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (1950 to 2013); EMBASE (1980 to 2013); AMED (Allied and Complementary Medicine) (1941 to 2013); CINAHL (Cumulative Index to Nursing and Allied Health Literature) (1937 to 2013). We also searched major clinical trials registers: CCT (http://www.controlled-trials.com); Clinical Trials (http://www.clinicaltrials.gov); Chinese Clinical Trial Register (www.chictr.org); ACTR (http://www.actr.org.au/. We examined the reference lists of all potentially relevant studies to identify further relevant trials. We handsearched published abstracts of conference proceedings from both the Dysphagia Research Society and the European Society of Swallowing Disorders. Digestive Disease Week (published in Gastroenterology) was also handsearched. Additionally, we searched ProQuest Dissertations & Theses for dissertation abstracts. Only randomised controlled trials were sought. Independent searches were completed by JR, AM, MC and MW. Two review authors (JR and MW) independently inspected titles, abstracts and key words identified from the literature search. No randomised controlled studies were retrieved. Twenty-nine studies were excluded, mainly on the basis of trial design. It was not possible to reach a conclusion on the efficacy and safety of botulinum toxin as an intervention for people with UOS dysfunction and neurological disease. There is insufficient evidence to inform clinical practice. Directions for future research are provided.

Registration status and outcome reporting of trials published in core headache medicine journals.

PubMed

Rayhill, Melissa L; Sharon, Roni; Burch, Rebecca; Loder, Elizabeth

2015-11-17

To evaluate randomized controlled trial (RCT) registration and outcome reporting compliance in core headache medicine journals. We identified RCTs published in core journals (Headache, Cephalalgia, and the Journal of Headache and Pain) from 2005 through 2014. We searched articles for trial registration numbers, which were verified in the corresponding trial registry. We categorized trial funding sources as industry, academic, government, or mixed. We contacted corresponding authors to assess reasons for nonregistration. We evaluated whether primary outcomes in trial registries matched those in corresponding publications. The journals published 225 RCTs over the study period. Fifty-eight of 225 (26%) reported a trial registration number in the article that could be linked to a corresponding registry entry. Trial registration rates increased over the 9 years of the study. Forty-six of 118 (39%) of industry-funded studies were registered compared with 27% of academic and 0% of government-funded studies. Only 5% of RCTs were prospectively registered, reported primary outcomes identical to those in the trial registry, and did not report unacknowledged post hoc outcomes. The most common reason for nonregistration was lack of awareness. Only about a quarter of the articles published in the core headache medicine journals are compliant with trial registration, but compliance has increased over time. Selective reporting of outcomes remains a problem, and very few trials met all 3 reporting standards assessed in this study. Efforts to improve the quality of trial reporting in the headache literature should continue. © 2015 American Academy of Neurology.

Practical issues regarding implementing a randomized clinical trial in a homeless population: strategies and lessons learned.

PubMed

Ojo-Fati, Olamide; Joseph, Anne M; Ig-Izevbekhai, Jed; Thomas, Janet L; Everson-Rose, Susan A; Pratt, Rebekah; Raymond, Nancy; Cooney, Ned L; Luo, Xianghua; Okuyemi, Kolawole S

2017-07-05

There is a critical need for objective data to guide effective health promotion and care for homeless populations. However, many investigators exclude homeless populations from clinical trials due to practical concerns about conducting research with this population. This report is based on our experience and lessons learned while conducting two large NIH-funded randomized controlled trials targeting smoking cessation among persons who are homeless. The current report also addresses challenges when conducting clinical trials among homeless populations and offers potential solutions. Homeless individuals face several challenges including the need to negotiate daily access to food, clothing, and shelter. Some of the critical issues investigators encounter include recruitment and retention obstacles; cognitive impairment, mental health and substance abuse disorders; transportation and scheduling challenges; issues pertaining to adequate study compensation; the need for safety protocols for study staff; and issues related to protecting the wellbeing of these potentially vulnerable adults. Anticipating realistic conditions in which to conduct studies with participants who are homeless will help investigators to design efficient protocols and may improve the feasibility of conducting clinical trials involving homeless populations and the quality of the data collected by the researchers. ClinicalTrials.gov, ID: NCT00786149 . Registered on 5 November 2008; ClinicalTrials.gov, ID: NCT01932996 . Registered on 20 November 2014.

Electroacupuncture for insomnia disorder: study protocol for a randomized controlled trial.

PubMed

Kim, Sung-Phil; Kim, Joo-Hee; Kim, Bo-Kyung; Kim, Hyeong-Jun; Jung, In Chul; Cho, Jung Hyo; Kim, Jung-Eun; Kim, Mi-Kyung; Kwon, O-Jin; Kim, Ae-Ran; Park, Hyo-Ju; Seo, Bok-Nam

2017-04-13

Insomnia is a common sleep disorder that affects many adults either transiently or chronically. The societal cost of insomnia is on the rise, while long-term use of current drug treatments can involve adverse effects. Recently, electroacupuncture (EA) has been used to treat various conditions including insomnia. The objective of this study is to provide scientific evidence for the effect and safety of using EA to treat insomnia. In this multicentre, assessor-blind, three-arm, parallel-design, randomised controlled trial, 150 participants will be assigned to the EA group, the sham EA (SEA) group, or the usual care group. The EA and SEA groups will receive the specific treatments 2-3 times a week for 4 weeks, for a total of 10 sessions, whereas the usual care group will not receive EA and will continue with usual care during the same time period. The primary outcome measure will be changes in the Insomnia Severity Index 5 weeks after randomisation. The secondary outcomes will include the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, a sleep diary, the EuroQoL-5 dimension questionnaire, the levels of melatonin and cortisol, and the Patient Global Impression of Change. Safety will be assessed at each visit. The results of this multicentre randomised controlled trial will contribute to provide rigorous clinical evidence for the effects and safety of EA for insomnia disorder. Korean Clinical Trial Registry, CRIS, KCT0001685 . Registered on 2 November 2015 (retrospectively registered). Date of enrolment of the first participant to the trial 13 October 2015.

Sirolimus Versus Tacrolimus as Primary Immunosuppressant After Renal Transplantation: A Meta-Analysis and Economics Evaluation.

PubMed

Liu, Jin-Yu; Song, Ming; Guo, Min; Huang, Feng; Ma, Bing-Jun; Zhu, Lan; Xu, Gang; Li, Juan; You, Ru-Xu

Sirolimus and tacrolimus are the major immunosuppressants for renal transplantation. Several studies have compared these 2 drugs, but the outcomes were not consistent. The aim of this study was to evaluate the efficacy, safety, and pharmacoeconomics of sirolimus and tacrolimus in the treatment of renal transplantation and provide evidence for the selection of essential drugs. Trials were identified through a computerized literature search of PubMed, EMBASE, Cochrane controlled trials register, Cochrane Renal Group Specialized Register of randomized controlled trials, and Chinese Biomedical database. Two independent reviewers assessed trials for eligibility and quality and then extracted data. Data were extracted for patient and graft mortality, acute rejection (AR), and adverse events. Dichotomous outcomes were reported as relative risk with 95% confidence intervals. A decision tree model was populated with data from a literature review and used to estimate costs and QALYs gained and incremental cost-effectiveness. Altogether, 1189 patients from 8 randomized controlled trials were included. The results of our analysis were that tacrolimus reduced the risks after renal transplantation of AR and patient withdrawn. Nevertheless, tacrolimus increased the risk of infection. Pharmacoeconomic analysis showed that tacrolimus represented a more cost-effective treatment than does cyclosporine for the prevention of adverse events after renal transplant. Tacrolimus is an effective and safe immunosuppressive agent, and it may be more cost-effective than cyclosporine for the primary prevention of AR in renal transplant recipients. However, it should be noted that such superiority was reversal when the cost of sirolimus and tacrolimus changed.

Tacrolimus Versus Cyclosporine as Primary Immunosuppressant After Renal Transplantation: A Meta-Analysis and Economics Evaluation.

PubMed

Liu, Jin-Yu; You, Ru-Xu; Guo, Min; Zeng, Lu; Zhou, Pu; Zhu, Lan; Xu, Gang; Li, Juan; Liu, Dong

2016-01-01

Tacrolimus and cyclosporine are the major immunosuppressants for renal transplantation. Several studies have compared these 2 drugs, but the outcomes were not consistent. The aim of this study was to evaluate the efficacy, safety, and pharmacoeconomics of cyclosporine and tacrolimus in the treatment of renal transplantation and provide evidence for the selection of essential drugs. Trials were identified through a computerized literature search of PubMed, EMBASE, Cochrane Controlled Trials Register, Cochrane Renal Group Specialized Register of randomized controlled trials, and Chinese Biomedical database. Two independent reviewers assessed trials for eligibility and quality and then extracted data. Data were extracted for patient and graft mortality, acute rejection, and adverse events. Dichotomous outcomes were reported as relative risk with 95% confidence intervals. A decision tree model was populated with data from a literature review and used to estimate costs and quality-adjusted life years gained and incremental cost-effectiveness. Altogether, 6137 patients from 27 randomized controlled trials were included. The results of our analysis were that tacrolimus reduced the risks after renal transplantation of patient mortality, graft loss, acute rejection, and hypercholesterolemia. Nevertheless, tacrolimus increased the risk of new-onset diabetes. Pharmacoeconomic analysis showed that tacrolimus represented a more cost-effective treatment than does cyclosporine for the prevention of adverse events following renal transplant. Tacrolimus is an effective and safe immunosuppressive agent and it may be more cost-effective than cyclosporine for the primary prevention of graft rejection in renal transplant recipients. However, new-onset diabetes should be closely monitored during the medication period.

Clinical Trials in Dentistry: A Cross-sectional Analysis of World Health Organization-International Clinical Trial Registry Platform.

PubMed

Sivaramakrishnan, Gowri; Sridharan, Kannan

2016-06-01

Clinical trials are the back bone for evidence-based practice (EBP) and recently EBP has been considered the best source of treatment strategies available. Clinical trial registries serve as databases of clinical trials. As regards to dentistry in specific data on the number of clinical trials and their quality is lacking. Hence, the present study was envisaged. Clinical trials registered in WHO-ICTRP (http://apps.who.int/trialsearch/AdvSearch.aspx) in dental specialties were considered. The details assessed from the collected trials include: Type of sponsors; Health condition; Recruitment status; Study design; randomization, method of randomization and allocation concealment; Single or multi-centric; Retrospective or prospective registration; and Publication status in case of completed studies. A total of 197 trials were identified. Maximum trials were from United States (n = 30) and United Kingdom (n = 38). Seventy six trials were registered in Clinical Trials.gov, 54 from International Standards of Reporting Clinical Trials, 13 each from Australia and New Zealand Trial Register and Iranian Registry of Clinical Trials, 10 from German Clinical Trial Registry, eight each from Brazilian Clinical Trial Registry and Nederland's Trial Register, seven from Japan Clinical Trial Registry, six from Clinical Trial Registry of India and two from Hong Kong Clinical Trial Registry. A total of 78.7% studies were investigator-initiated and 64% were completed while 3% were terminated. Nearly four-fifths of the registered trials (81.7%) were interventional studies of which randomized were the large majority (94.4%) with 63.2% being open label, 20.4% using single blinding technique and 16.4% were doubled blinded. The number, methodology and the characteristics of clinical trials in dentistry have been noted to be poor especially in terms of being conducted multi-centrically, employing blinding and the method for randomization and allocation concealment. More emphasis has to be laid down on the quality of trials being conducted in order to provide justice in the name of EBP. Copyright © 2016 Elsevier Inc. All rights reserved.

Compliance with prospective trial registration guidance remained low in high-impact journals and has implications for primary end point reporting.

PubMed

Dal-Ré, Rafael; Ross, Joseph S; Marušić, Ana

2016-07-01

To examine compliance with International Committee of Medical Journal Editors' (ICMJE) policy on prospective trial registration along with predictors of compliance. Cross-sectional analysis of all articles reporting trial results published in the six highest-impact general medicine journals in January-June 2014 that were registered in a public trial registry. The main outcome measure was compliance with ICMJE policy. The time frame for trial primary end point ascertainment was used to assess whether retrospective registration could have allowed changing of primary end points following an interim analysis. Forty of 144 (28%) articles did not comply with the ICMJE policy. Trials of non-FDA-regulated interventions were less compliant than trials of FDA-regulated interventions (i.e., medicines, medical devices) (42% vs. 21%; P = 0.016). Twenty-nine of these 40 (72%; 20% overall) were registered before any interim analysis of primary end points could have been conducted; 11 (28%; 8% overall) were registered after primary end point ascertainment, such that investigators could have had the opportunity to conduct an interim analysis before trial registration. Twenty-eight percent of trials published in high-impact journals were retrospectively registered including nearly 10% that were registered after primary end point ascertainment could have had taken place. Prospective registration should be prompted and enforced to ensure transparency and accountability in clinical research. Copyright © 2016 Elsevier Inc. All rights reserved.

Systematic review of interventional sickle cell trials registered in ClinicalTrials.gov.

PubMed

Lebensburger, Jeffrey D; Hilliard, Lee M; Pair, Lauren E; Oster, Robert; Howard, Thomas H; Cutter, Gary R

2015-12-01

The registry ClinicalTrials.gov was created to provide investigators and patients an accessible database of relevant clinical trials. To understand the state of sickle cell disease clinical trials, a comprehensive review of all 174 "closed," "interventional" sickle cell trials registered at ClinicalTrials.gov was completed in January 2015. The majority of registered sickle cell disease clinical trials listed an academic center as the primary sponsor and were an early phase trial. The primary outcome for sickle cell disease trials focused on pain (23%), bone marrow transplant (BMT) (13%), hydroxyurea (8%), iron overload (8%), and pulmonary hypertension (8%). A total of 52 trials were listed as terminated or withdrawn, including 25 (14% of all trials) terminated for failure to enroll participants. At the time of this review, only 19 trials uploaded results and 29 trials uploaded a manuscript in the ClinicalTrials.gov database. A systematic review of pubmed.gov revealed that only 35% of sickle cell studies completed prior to 2014 resulted in an identified manuscript. In comparison, of 80 thalassemia trials registered in ClinicalTrials.gov, four acknowledged failure to enroll participants as a reason for trial termination or withdrawal, and 48 trials (60%) completed prior to 2014 resulted in a currently identified manuscript. ClinicalTrials.gov can be an important database for investigators and patients with sickle cell disease to understand the current available research trials. To enhance the validity of the website, investigators must update their trial results and upload trial manuscripts into the database. This study, for the first time, quantifies outcomes of sickle cell disease trials and provides support to the belief that barriers exist to successful completion, publication, and dissemination of sickle cell trial results. © The Author(s) 2015.

Mirror therapy for improving motor function after stroke.

PubMed

Thieme, Holm; Mehrholz, Jan; Pohl, Marcus; Behrens, Johann; Dohle, Christian

2012-03-14

Mirror therapy is used to improve motor function after stroke. During mirror therapy, a mirror is placed in the patient's midsagittal plane, thus reflecting movements of the non-paretic side as if it were the affected side. To summarise the effectiveness of mirror therapy for improving motor function, activities of daily living, pain and visuospatial neglect in patients after stroke. We searched the Cochrane Stroke Group's Trials Register (June 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (1950 to June 2011), EMBASE (1980 to June 2011), CINAHL (1982 to June 2011), AMED (1985 to June 2011), PsycINFO (1806 to June 2011) and PEDro (June 2011). We also handsearched relevant conference proceedings, trials and research registers, checked reference lists and contacted trialists, researchers and experts in our field of study. We included randomised controlled trials (RCTs) and randomised cross-over trials comparing mirror therapy with any control intervention for patients after stroke. Two review authors independently selected trials based on the inclusion criteria, documented the methodological quality of studies and extracted data. We analysed the results as standardised mean differences (SMDs) for continuous variables. We included 14 studies with a total of 567 participants that compared mirror therapy with other interventions. When compared with all other interventions, mirror therapy may have a significant effect on motor function (post-intervention data: SMD 0.61; 95% confidence interval (CI) 0.22 to 1.0; P = 0.002; change scores: SMD 1.04; 95% CI 0.57 to 1.51; P < 0.0001). However, effects on motor function are influenced by the type of control intervention. Additionally, mirror therapy may improve activities of daily living (SMD 0.33; 95% CI 0.05 to 0.60; P = 0.02). We found a significant positive effect on pain (SMD -1.10; 95% CI -2.10 to -0.09; P = 0.03) which is influenced by patient population. We found limited evidence for improving visuospatial neglect (SMD 1.22; 95% CI 0.24 to 2.19; P = 0.01). The effects on motor function were stable at follow-up assessment after six months. The results indicate evidence for the effectiveness of mirror therapy for improving upper extremity motor function, activities of daily living and pain, at least as an adjunct to normal rehabilitation for patients after stroke. Limitations are due to small sample sizes of most included studies, control interventions that are not used routinely in stroke rehabilitation and some methodological limitations of the studies.

Effects of improved sanitation on diarrheal reduction for children under five in Idiofa, DR Congo: a cluster randomized trial.

PubMed

Cha, Seungman; Lee, JaeEun; Seo, DongSik; Park, Byoung Mann; Mansiangi, Paul; Bernard, Kabore; Mulakub-Yazho, Guy Jerome Nkay; Famasulu, Honore Minka

2017-09-19

The lack of safe water and sanitation contributes to the rampancy of diarrhea in many developing countries. This study describes the design of a cluster-randomized trial in Idiofa, the Democratic Republic of the Congo, seeking evidence of the impact of improved sanitation on diarrhea for children under four. Of the 276 quartiers, 18 quartiers were randomly allocated to the intervention or control arm. Seven hundred and-twenty households were sampled and the youngest under-four child in each household was registered for this study. The primary endpoint of the study is diarrheal incidence, prevalence and duration in children under five. Material subsidies will be provided only to the households who complete pit digging plus superstructure and roof construction, regardless of their income level. This study employs a Sanitation Calendar so that the mother of each household can record the diarrheal episodes of her under-four child on a daily basis. The diary enables examination of the effect of the sanitation intervention on diarrhea duration and also resolves the limitation of the small number of clusters in the trial. In addition, the project will be monitored through the 'Sanitation Map', on which all households in the study area, including both the control and intervention arms, are registered. To avoid information bias or courtesy bias, photos will be taken of the latrine during the household visit, and a supervisor will determine well-equipped latrine uptake based on the photos. This reduces the possibility of recall bias and under- or over-estimation of diarrhea, which was the main limitation of previous studies. The study was approved by the Institutional Review Board of the School of Public Health, Kinshasa University (ESP/CE/040/15; April 13, 2015) and registered as an International Standard Randomized Controlled Trial (ISRCTN: 10,419,317) on March 13, 2015.

Inadequate safety reporting in pre-eclampsia trials: a systematic evaluation.

PubMed

Duffy, Jmn; Hirsch, M; Pealing, L; Showell, M; Khan, K S; Ziebland, S; McManus, R J

2018-06-01

Randomised trials and their syntheses in meta-analyses offer a unique opportunity to assess the frequency and severity of adverse reactions. To assess safety reporting in pre-eclampsia trials. Systematic search using bibliographic databases, including Cochrane Central Register of Controlled Trials, Embase, and MEDLINE, from inception to August 2017. Randomised trials evaluating anticonvulsant or antihypertensive medication for pre-eclampsia. Descriptive statistics appraising the adequacy of adverse reaction and toxicity reporting. We included 60 randomised trials. Six trials (10%) were registered with the International Clinical Trials Registry Platform, two registry records referred to adverse reactions, stating 'safety and toleration' and 'possible side effects' would be collected. Twenty-six trials (43%) stated the frequency of withdrawals within each study arm, and five trials (8%) adequately reported these withdrawals. Adverse reactions were inconsistently reported across eligible trials: 24 (40%) reported no serious adverse reactions and 36 (60%) reported no mild adverse reactions. The methods of definition or measurement of adverse reactions were infrequently reported within published trial reports. Pre-eclampsia trials regularly omit critical information related to safety. Despite the paucity of reporting, randomised trials collect an enormous amount of safety data. Developing and implementing a minimum data set could help to improve safety reporting, permitting a more balanced assessment of interventions by considering the trade-off between the benefits and harms. National Institute for Health Research (DRF-2014-07-051), UK; Maternity Forum, Royal Society of Medicine, UK. Developing @coreoutcomes could help to improve safety reporting in #preeclampsia trials. @NIHR_DC. © 2017 Royal College of Obstetricians and Gynaecologists.

Efficacy of physical exercise in preventing falls in older adults with cognitive impairment: a systematic review and meta-analysis.

PubMed

Chan, Wai Chi; Yeung, Jerry Wing Fai; Wong, Corine Sau Man; Lam, Linda Chiu Wa; Chung, Ka Fai; Luk, James Ka Hay; Lee, Jenny Shun Wah; Law, Andrew Chi Kin

2015-02-01

Numerous studies have reported the prevention of falls through exercise among cognitively healthy older people. This study aimed to determine whether the current evidence supports that physical exercise is also efficacious in preventing falls in older adults with cognitive impairment. Two independent reviewers searched MEDLINE; EMBASE; PsycINFO; the Cumulative Index to Nursing & Allied Health Literature; the Cochrane Central Register of Controlled Trials; the Cochrane Bone, Joint, and Muscle Trauma Group Specialized Register; ClinicalTrials.gov; and the UK Clinical Research Network Study Portfolio up to July 2013 without language restriction. We included randomized controlled trials that examined the efficacy of physical exercise in older adults with cognitive impairment. The methodological qualities of the included trials were appraised according to the criteria developed for the Cochrane review of fall prevention trials. The primary outcome measure was the rate ratio of falls. A meta-analysis was performed to estimate the pooled rate ratio and summarize the results of the trials on fall prevention through physical exercise. Seven randomized controlled trials involving 781 participants were included, 4 of which examined solely older people with cognitive impairment. Subgroup data on persons with cognitive impairment were obtained from the other 3 trials that targeted older populations in general. The meta-analysis showed that physical exercise had a significant effect in preventing falls in older adults with cognitive impairment, with a pooled estimate of rate ratio of 0.68 (95% confidence interval 0.51-0.91). The present analysis suggests that physical exercise has a positive effect on preventing falls in older adults with cognitive impairment. Further studies will be required to determine the modality and frequency of exercise that are optimal for the prevention of falls in this population. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Complementary and alternative therapies for pain management in labour.

PubMed

Smith, C A; Collins, C T; Cyna, A M; Crowther, C A

2003-01-01

Many women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute towards the popularity of complementary methods of pain management. This review examined currently available evidence supporting the use of alternative and complementary therapies for pain management in labour. To examine the effectiveness of complementary and alternative therapies for pain management in labour on maternal and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group trials register (July 2002), the Cochrane Controlled Trials Register (The Cochrane Library Issue 2, 2002), MEDLINE (1966 to July 2002), EMBASE (1980 to July 2002) and CINAHL (1980 to July 2002). The inclusion criteria included published and unpublished randomised controlled trials comparing complementary and alternative therapies with placebo, no treatment or pharmacological forms of pain management in labour. All women whether primiparous or multiparous, and in spontaneous or induced labour, in the first and second stage of labour were included. Meta-analysis was performed using relative risks for dichotomous outcomes and weighted mean differences for continuous outcomes. The outcome measures were maternal satisfaction, use of pharmacological pain relief and maternal and neonatal adverse outcomes. Seven trials involving 366 women and using different modalities of pain management were included in this review. The trials included one involving acupuncture (n = 100), one involving audio-analgesia (n = 25), one involving aromatherapy (n = 22), three trials of hypnosis (n = 189) and one trial of music (n = 30). The trial of acupuncture decreased the need for pain relief (relative risk (RR) 0.56, 95% confidence interval (CI) 0.39 to 0.81). Women receiving hypnosis were more satisfied with their pain management in labour compared with controls (RR 2.33, 95% CI 1.55 to 4.71). No differences were seen for women receiving aromatherapy, music or audio analgesia. Acupuncture and hypnosis may be beneficial for the management of pain during labour. However, few complementary therapies have been subjected to proper scientific study and the number of women studied is small.

The transvaginal hybrid NOTES versus conventionally assisted laparoscopic sigmoid resection for diverticular disease (TRANSVERSAL) trial: study protocol for a randomized controlled trial.

PubMed

Senft, Jonas D; Warschkow, Rene; Diener, Markus K; Tarantino, Ignazio; Steinemann, Daniel C; Lamm, Sebastian; Simon, Thomas; Zerz, Andreas; Müller-Stich, Beat P; Linke, Georg R

2014-11-20

Natural orifice transluminal endoscopic surgery (NOTES) is the consequence of further development of minimally invasive surgery to reduce abdominal incisions and surgical trauma. The potential benefits are expected to be less postoperative pain, faster convalescence, and reduced risk for incisional hernias and wound infections compared to conventional methods. Recent clinical studies have demonstrated the feasibility and safety of transvaginal NOTES, and transvaginal access is currently the most frequent clinically applied route for NOTES procedures. However, despite increasing clinical application, no firm clinical evidence is available for objective assessment of the potential benefits and risks of transvaginal NOTES compared to the current surgical standard. The TRANSVERSAL trial is designed as a randomized controlled trial to compare transvaginal hybrid NOTES and laparoscopic-assisted sigmoid resection. Female patients referred to elective sigmoid resection due to complicated or reoccurring diverticulitis of the sigmoid colon are considered eligible. The primary endpoint will be pain intensity during mobilization 24 hours postoperatively as measured by the blinded patient and blinded assessor on a visual analogue scale (VAS). Secondary outcomes include daily pain intensity and analgesic use, patient mobility, intraoperative complications, morbidity, length of stay, quality of life, and sexual function. Follow-up visits are scheduled 3, 12, and 36 months after surgery. A total sample size of 58 patients was determined for the analysis of the primary endpoint. The confirmatory analysis will be performed based on the intention-to-treat (ITT) principle. The TRANSVERSAL trial is the first study to compare transvaginal hybrid NOTES and conventionally assisted laparoscopic surgery for colonic resection in a randomized controlled setting. The results of the TRANSVERSAL trial will allow objective assessment of the potential benefits and risks of NOTES compared to the current surgical standard for sigmoid resection. The trial protocol was registered in the German Clinical Trials Register ( DRKS00005995) on March 27, 2014.

Effects of an 18-week exercise programme started early during breast cancer treatment: a randomised controlled trial.

PubMed

Travier, Noémie; Velthuis, Miranda J; Steins Bisschop, Charlotte N; van den Buijs, Bram; Monninkhof, Evelyn M; Backx, Frank; Los, Maartje; Erdkamp, Frans; Bloemendal, Haiko J; Rodenhuis, Carla; de Roos, Marnix A J; Verhaar, Marlies; ten Bokkel Huinink, Daan; van der Wall, Elsken; Peeters, Petra H M; May, Anne M

2015-06-08

Exercise started shortly after breast cancer diagnosis might prevent or diminish fatigue complaints. The Physical Activity during Cancer Treatment (PACT) study was designed to primarily examine the effects of an 18-week exercise intervention, offered in the daily clinical practice setting and starting within 6 weeks after diagnosis, on preventing an increase in fatigue. This multi-centre controlled trial randomly assigned 204 breast cancer patients to usual care (n = 102) or supervised aerobic and resistance exercise (n = 102). By design, all patients received chemotherapy between baseline and 18 weeks. Fatigue (i.e., primary outcome at 18 weeks), quality of life, anxiety, depression, and physical fitness were measured at 18 and 36 weeks. Intention-to-treat mixed linear model analyses showed that physical fatigue increased significantly less during cancer treatment in the intervention group compared to control (mean between-group differences at 18 weeks: -1.3; 95 % CI -2.5 to -0.1; effect size -0.30). Results for general fatigue were comparable but did not reach statistical significance (-1.0, 95%CI -2.1; 0.1; effect size -0.23). At 18 weeks, submaximal cardiorespiratory fitness and several muscle strength tests (leg extension and flexion) were significantly higher in the intervention group compared to control, whereas peak oxygen uptake did not differ between groups. At 36 weeks these differences were no longer statistically significant. Quality of life outcomes favoured the exercise group but were not significantly different between groups. A supervised 18-week exercise programme offered early in routine care during adjuvant breast cancer treatment showed positive effects on physical fatigue, submaximal cardiorespiratory fitness, and muscle strength. Exercise early during treatment of breast cancer can be recommended. At 36 weeks, these effects were no longer statistically significant. This might have been caused by the control participants' high physical activity levels during follow-up. Current Controlled Trials ISRCTN43801571, Dutch Trial Register NTR2138. Trial registered on December 9th, 2009.

Is Mandatory Prospective Trial Registration Working to Prevent Publication of Unregistered Trials and Selective Outcome Reporting? An Observational Study of Five Psychiatry Journals That Mandate Prospective Clinical Trial Registration.

PubMed

Scott, Amelia; Rucklidge, Julia J; Mulder, Roger T

2015-01-01

To address the bias occurring in the medical literature associated with selective outcome reporting, in 2005, the International Committee of Medical Journal Editors (ICMJE) introduced mandatory trial registration guidelines and member journals required prospective registration of trials prior to patient enrolment as a condition of publication. No research has examined whether these guidelines are impacting psychiatry publications. Our objectives were to determine the extent to which articles published in psychiatry journals adhering to ICMJE guidelines were correctly prospectively registered, whether there was evidence of selective outcome reporting and changes to participant numbers, and whether there was a relationship between registration status and source of funding. Any clinical trial (as defined by ICMJE) published between 1 January 2009 and 31 July 2013 in the top five psychiatry journals adhering to ICMJE guidelines (The American Journal of Psychiatry, Archives of General Psychiatry/JAMA Psychiatry, Biological Psychiatry, Journal of the American Academy of Child and Adolescent Psychiatry, and The Journal of Clinical Psychiatry) and conducted after July 2005 (or 2007 for two journals) was included. For each identified trial, where possible we extracted trial registration information, changes to POMs between publication and registry to assess selective outcome reporting, changes to participant numbers, and funding type. Out of 3305 articles, 181 studies were identified as clinical trials requiring registration: 21 (11.6%) were deemed unregistered, 61 (33.7%) were retrospectively registered, 37 (20.4%) had unclear POMs either in the article or the registry and 2 (1.1%) were registered in an inaccessible trial registry. Only 60 (33.1%) studies were prospectively registered with clearly defined POMs; 17 of these 60 (28.3%) showed evidence of selective outcome reporting and 16 (26.7%) demonstrated a change in participant numbers of 20% or more; only 26 (14.4%) of the 181 the trials were prospectively registered and did not alter their POMs or the time frames at which they were measured. Prospective registration with no changes in POMs occurred more frequently with pharmaceutical funding. Although standards are in place to improve prospective registration and transparency in clinical trials, less than 15% of psychiatry trials were prospectively registered with no changes in POMs. Most trials were either not prospectively registered, changed POMs or the timeframes at some point after registration or changed participant numbers. Authors, journal editors and reviewers need to further efforts to highlight the value of prospective trial registration.

Effects of advanced life support versus basic life support on the mortality rates of patients with trauma in prehospital settings: a study protocol for a systematic review and meta-analysis

PubMed Central

Kondo, Yutaka; Fukuda, Tatsuma; Uchimido, Ryo; Hifumi, Toru; Hayashida, Kei

2017-01-01

Introduction Advanced life support (ALS) is thought to be associated with improved survival in prehospital trauma care when compared with basic life support (BLS). However, evidence on the benefits of prehospital ALS for patients with trauma is controversial. Therefore, we aim to clarify if ALS improves mortality in patients with trauma when compared with BLS by conducting a systematic review and meta-analysis of the recent literature. Methods and analysis We will perform searches in PubMed, Embase and the Cochrane Central Register of Controlled Trials for published observational studies, controlled before-and-after studies, randomised controlled trials and other controlled trials conducted in humans and published until March 2017. We will screen search results, assess study selection, extract data and assess the risk of bias in duplicate; disagreements will be resolved through discussions. Data from clinically homogeneous studies will be pooled using a random-effects meta-analysis, heterogeneity of effects will be assessed using the χ2 test of homogeneity, and any observed heterogeneity will be quantified using the I2 statistic. Last, the Grading of Recommendations Assessment, Development and Evaluation approach will be used to rate the quality of the evidence. Ethics and dissemination Our study does not require ethical approval as it is based on findings of previously published articles. Results will be disseminated through publication in a peer-reviewed journal, presentations at relevant conferences and publications for patient information. Trial registration number PROSPERO (International Prospective Register of Systematic Reviews) registration number CRD42017054389. PMID:29061611

Environmental sanitary interventions for preventing active trachoma.

PubMed

Rabiu, Mansur; Alhassan, Mahmoud B; Ejere, Henry O D; Evans, Jennifer R

2012-02-15

Trachoma is a major cause of avoidable blindness. It is responsible for about six million blind people worldwide, mostly in the poor communities of developing countries. One of the major strategies advocated for the control of the disease is the application of various environmental sanitary measures to such communities. To assess the evidence for the effectiveness of environmental sanitary measures on the prevalence of active trachoma in endemic areas. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 9), MEDLINE (January 1950 to September 2011), EMBASE (January 1980 to September 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to September 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 23 September 2011. We checked the reference list of included trials and the Science Citation Index. We also contacted agencies, experts and researchers in trachoma control. We included randomised and quasi-randomised controlled trials comparing any form of environmental hygiene measures with no measure. These hygiene measures included fly control, provision of water and health education. Participants in the trials were people normally resident in the trachoma endemic areas. Two authors independently extracted data and assessed the quality of the included trials. Study authors were contacted for additional information. Six trials met the inclusion criteria but we did not conduct meta-analysis due to heterogeneity of the studies. We included six studies with a total of 12,294 participants from 79 communities. Two studies that assessed insecticide spray as a fly control measure found that trachoma is reduced by at least 55% to 61% with this measure compared to no intervention. However, another study did not find insecticide spray to be effective in reducing trachoma. One study found that another fly control measure, latrine provision, reduced trachoma by 29.5% compared to no intervention; this was, however, not statistically significantly different and findings have not been confirmed by a more recent study. Another study revealed that health education reduced the incidence of trachoma. These findings were not confirmed by a second study, however, which found that a modest health education programme with modest water supply did not reduce trachoma. However, all the studies have some methodological concerns. There is some evidence from two trials that insecticides are effective in reducing trachoma, however, this effect was not demonstrated in another trial that used insecticides. Two trials on latrine provision as a fly control measure have not demonstrated significant trachoma reduction. Health education had shown significant reduction of trachoma in one study but another study did not demonstrate similar findings. Generally there is a dearth of data to determine the effectiveness of all aspects of environmental sanitation in the control of trachoma.

Corticosteroids for the common cold.

PubMed

Hayward, Gail; Thompson, Matthew J; Perera, Rafael; Del Mar, Chris B; Glasziou, Paul P; Heneghan, Carl J

2015-10-13

The common cold is a frequent illness, which, although benign and self limiting, results in many consultations to primary care and considerable loss of school or work days. Current symptomatic treatments have limited benefit. Corticosteroids are an effective treatment in other upper respiratory tract infections and their anti-inflammatory effects may also be beneficial in the common cold. This updated review has included one additional study. To compare corticosteroids versus usual care for the common cold on measures of symptom resolution and improvement in children and adults. We searched Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 4), which includes the Acute Respiratory Infections (ARI) Group's Specialised Register, the Database of Reviews of Effects (DARE) (2015, Issue 2), NHS Health Economics Database (2015, Issue 2), MEDLINE (1948 to May week 3, 2015) and EMBASE (January 2010 to May 2015). Randomised, double-blind, controlled trials comparing corticosteroids to placebo or to standard clinical management. Two review authors independently extracted data and assessed trial quality. We were unable to perform meta-analysis and instead present a narrative description of the available evidence. We included three trials (353 participants). Two trials compared intranasal corticosteroids to placebo and one trial compared intranasal corticosteroids to usual care; no trials studied oral corticosteroids. In the two placebo-controlled trials, no benefit of intranasal corticosteroids was demonstrated for duration or severity of symptoms. The risk of bias overall was low or unclear in these two trials. In a trial of 54 participants, the mean number of symptomatic days was 10.3 in the placebo group, compared to 10.7 in those using intranasal corticosteroids (P value = 0.72). A second trial of 199 participants reported no significant differences in the duration of symptoms. The single-blind trial in children aged two to 14 years, who were also receiving oral antibiotics, had inadequate reporting of outcome measures regarding symptom resolution. The overall risk of bias was high for this trial. Mean symptom severity scores were significantly lower in the group receiving intranasal steroids in addition to oral amoxicillin. One placebo-controlled trial reported the presence of rhinovirus in nasal aspirates and found no differences. Only one of the three trials reported on adverse events; no differences were found. Two trials reported secondary bacterial infections (one case of sinusitis, one case of acute otitis media; both in the corticosteroid groups). A lack of comparable outcome measures meant that we were unable to combine the data. Current evidence does not support the use of intranasal corticosteroids for symptomatic relief from the common cold. However, there were only three trials, one of which was very poor quality, and there was limited statistical power overall. Further large, randomised, double-blind, placebo-controlled trials in adults and children are required to answer this question.

The effectiveness of Hibiscus sabdariffa in the treatment of hypertension: a systematic review.

PubMed

Wahabi, H A; Alansary, L A; Al-Sabban, A H; Glasziuo, P

2010-02-01

Hypertension is a common global health problem with significant mortality and morbidity. Hibiscus sabdariffa is a plant known in many countries and is consumed as hot and cold drinks In addition to its use in folk medicine; it has been suggested as treatment for many conditions including hypertension. The objectives of this review were to examine the evidence of effectiveness and safety of hibiscus in the treatment of hypertension. We searched several medical databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and the specialized register of the Cochrane Hypertension Group and the general engine Google) to January 2009. We included randomized controlled trials that had examined Hibiscus's effectiveness and safety in the treatment of primary hypertension in adults. Two authors independently selected the trials for the review, extracted the data, and critically appraised the included studies. Four trials, with a total of 390 patients, met our inclusion criteria. Two studies compared Hibiscus sabdariffa to black tea; one study compared it to captopril and one to lisinopril. The studies found that Hibiscus had greater blood pressure reduction than tea but less than the ACE-inhibitors. However, all studies, except one, were short term and of poor quality with a Jadad scoring of <3 and did not meet international standards. The four randomized controlled studies identified in this review do not provide reliable evidence to support recommending Hibiscus sabdariffa for the treatment of primary hypertension in adults. Copyright 2009 Elsevier GmbH. All rights reserved.

Interventions for enhancing consumers' online health literacy.

PubMed

Car, Josip; Lang, Britta; Colledge, Anthea; Ung, Chuin; Majeed, Azeem

2011-06-15

Access to health information is critical to enable consumers to participate in decisions on health. Increasingly, such information is accessed via the internet, but a number of barriers prevent consumers making effective use of it. These barriers include inadequate skills to search, evaluate and use the information. It has not yet been demonstrated whether training consumers to use the internet for health information can result in positive health outcomes. To assess the effects of interventions for enhancing consumers' online health literacy (skills to search, evaluate and use online health information). We searched: the Cochrane Consumers and Communication Review Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1 2008); MEDLINE (Ovid); EMBASE (Ovid); CINAHL (Dialog); ERIC (CSA Illumina); LISA (CSA Illumina); PsycINFO (Ovid); Index to scientific and technical proceedings; SIGLE; ASLIB Index to Theses; ProQuest Dissertation Abstracts; National Research Register/UK CRN Portfolio database; Current Controlled Trials - MetaRegister of Controlled Trials. We searched all databases for the period January 1990 to March 2008. Randomised controlled trials (RCTs), cluster RCTs and associated economic evaluations, quasi-RCTs, interrupted time series analyses, and controlled before and after (CBA) studies assessing interventions to enhance consumers' online health literacy, in any language. Two review authors independently selected studies for inclusion, assessed their quality and extracted data. We contacted study authors for clarification and to seek missing data. We presented results as a narrative and tabular summary, and calculated mean differences where appropriate. We included two studies: one randomised controlled trial (RCT) and one controlled before and after (CBA) study with a combined total of 470 participants. The RCT compared internet health information classes with patient education classes for participants with HIV infection. Only the RCT, which we rated as having a moderate risk of bias, reported statistically significant positive effects for primary outcomes related to online health literacy in the intervention group, for the following outcomes: 'Self-efficacy for health information seeking', 'health information evaluation skills' and the 'number of times the patient discussed online information with a health provider'. The CBA, which we rated as having a high risk of bias, compared internet health information classes with a control group receiving no intervention among healthy adults aged 50+. It showed significant positive changes only in a secondary (behavioural) outcome in the intervention group, regarding the readiness to adopt the internet as a tool for preventive health information. No adverse effects were reported.There is low quality evidence that such interventions may improve some outcomes relevant to online health literacy in certain populations. Due to the small number of studies and their variable methodological quality, the evidence is too weak to draw any conclusions about implications for the design and delivery of interventions for online health literacy. There is a need for well-designed RCTs to investigate the effects of such interventions. These should involve different participants (in terms of disease status, age, socio-economic group and gender) to analyse the extent to which online health literacy reduces a barrier to using the internet for health information. Trials should be conducted in different settings and should examine interventions to enhance consumers' online health literacy (search, appraisal and use of online health information) like internet training courses, measuring outcomes up to at least one year after the intervention to estimate the sustainability of the intervention effects.

Study Protocol – Metabolic syndrome, vitamin D and bone status in South Asian women living in Auckland, New Zealand: A randomised, placebo-controlled, double-blind vitamin D intervention

PubMed Central

von Hurst, Pamela R; Stonehouse, Welma; Matthys, Christophe; Conlon, Cathryn; Kruger, Marlena C; Coad, Jane

2008-01-01

Background The identification of the vitamin D receptor in the endocrine pancreas suggests a role for vitamin D in insulin secretion. There is also some limited evidence that vitamin D influences insulin resistance, and thus the early stages of the development of type 2 diabetes. Methods Eighty-four women of South Asian origin, living in Auckland, New Zealand, were randomised to receive either a supplement (4000IU 25(OH)D3 per day) or a placebo for 6 months. At baseline, all participants were vitamin D deficient (serum 25(OH)D3 <50 nmol/L), insulin resistant (HOMA-IR > 1.93) and/or hyperinsulinaemic, hyperglycemic or had clinical signs of dislipidaemia. Changes in HOMA-IR, lipids, parathyroid hormone, calcium and bone markers were monitored at 3 months and 6 months. Discussion This randomised, controlled trial will be the first to investigate the effect of vitamin D supplementation on insulin resistance in non-diabetic subjects. It will subsequently contribute to the growing body of evidence about the role of vitamin D in metabolic syndrome.Registered clinical. Trial registration Registered clinical trial – Registration No. ACTRN12607000642482 PMID:18667086

Topiramate's effectiveness on weight reduction in overweight/obese persons with schizophrenia: study protocol for a randomized controlled trial.

PubMed

Chandradasa, Miyuru; Champika, Layani; de Silva, Silumini; Kuruppuarachchi, K A L A

2017-09-20

Schizophrenia is a psychiatric disorder with a higher mortality than that of the general population. Most of the deaths are due to cardiovascular causes and are related to metabolic risks. This risk is due not only to antipsychotics but also to inherent factors of the disorder. Studies in the West have shown topiramate to be effective in schizophrenia to reduce weight gain and for symptomatic control. Whether this is effective for South Asians is not known. It is important because South Asians have a higher risk of metabolic syndrome. We aim to conduct a double-blind, randomized controlled trial comparing topiramate add-on therapy with treatment as usual with antipsychotics in patients with schizophrenia in an outpatient setting in Sri Lanka. Ninety patients with schizophrenia presenting to the Colombo North Teaching Hospital will be randomized to intervention and control groups equally using permuted block randomization. Patients with comorbid metabolic disorders and taking prescribed weight-controlling medications will be excluded. The intervention group will be prescribed topiramate in addition to their antipsychotics in a predefined dosing regimen targeting a dose of 100 mg per day. The control subjects are to receive a placebo. As the primary outcome, anthropometric measurements including weight, waist circumference, skinfold thickness, and body mass index will be recorded at baseline and monthly during the study period of 3 months. The secondary outcome is the change in symptoms according to the clinician-administered Brief Psychiatric Rating Scale. Assessment of capacity will be performed and informed consent obtained from all subjects. Ethics approval has been obtained from the ethical review committee of the Faculty of Medicine, University of Kelaniya, and the trial has been registered in the Sri Lanka Clinical Trials Registry. In this double-blind, randomized controlled trial, we will attempt to assess the effectiveness of topiramate as an add-on therapy compared with treatment as usual for weight control in patients with schizophrenia. To our knowledge, this is the first such study in South Asia, where metabolic risks are found to be higher than in the West and could have unique ethnic factors related to weight gain in schizophrenia. Sri Lanka Clinical Trials Registry, SLCTR/2017/003 . Registered on 20 February 2017. Universal trial number, U1111-1192-9439.

Protocol for economic evaluation alongside a cluster-randomised controlled trial of a psychoeducational intervention for the primary prevention of postnatal mental health problems in first-time mothers.

PubMed

Ride, Jemimah; Rowe, Heather; Wynter, Karen; Fisher, Jane; Lorgelly, Paula

2014-10-03

Postnatal mental health problems, which are an international public health priority, are a suitable target for preventive approaches. The financial burden of these disorders is borne across sectors in society, including health, early childhood, education, justice and the workforce. This paper describes the planned economic evaluation of What Were We Thinking, a psychoeducational intervention for the prevention of postnatal mental health problems in first-time mothers. The evaluation will be conducted alongside a cluster-randomised controlled trial of its clinical effectiveness. Cost-effectiveness and costs-utility analyses will be conducted, resulting in estimates of cost per percentage point reduction in combined 30-day prevalence of depression, anxiety and adjustment disorders and cost per quality-adjusted life year gained. Uncertainty surrounding these estimates will be addressed using non-parametric bootstrapping and represented using cost-effectiveness acceptability curves. Additional cost analyses relevant for implementation will also be conducted. Modelling will be employed to estimate longer term cost-effectiveness if the intervention is found to be clinically effective during the period of the trial. Approval to conduct the study was granted by the Southern Health (now Monash Health) Human Research Ethics Committee (24 April 2013; 11388B). The study was registered with the Monash University Human Research Ethics Committee (30 April 2013; CF12/1022-2012000474). The Education and Policy Research Committee, Victorian Government Department of Education and Early Childhood Development approved the study (22 March 2012; 2012_001472). Use of the EuroQol was registered with the EuroQol Group; 16 August 2012. The trial was registered with the Australian New Zealand Clinical Trials Registry on 7 May 2012 (registration number ACTRN12613000506796). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Motivational interviewing for improving recovery after stroke.

PubMed

Cheng, Daobin; Qu, Zhanli; Huang, Jianyi; Xiao, Yousheng; Luo, Hongye; Wang, Jin

2015-06-03

Psychological problems are common complications following stroke that can cause stroke survivors to lack the motivation to take part in activities of daily living. Motivational interviewing provides a specific way for enhancing intrinsic motivation, which may help to improve activities of daily living for stroke survivors. To investigate the effect of motivational interviewing for improving activities of daily living after stroke. We searched the Cochrane Stroke Group's Trials Register (November 2014), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 1), MEDLINE (1948 to March 2015), EMBASE (1980 to March 2015), CINAHL (1982 to March 2015), AMED (1985 to March 2015), PsycINFO (1806 to March 2015), PsycBITE (March 2015) and four Chinese databases. In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers and conference proceedings, checked reference lists, and contacted authors of relevant studies. Randomised controlled trials (RCTs) comparing motivational interviewing with no intervention, sham motivational interviewing or other psychological therapy for people with stroke were eligible. Two review authors independently selected studies for inclusion, extracted eligible data and assessed risk of bias. Outcome measures included activities of daily living, mood and death. One study involving a total of 411 participants, which compared motivational interviewing with usual care, met our inclusion criteria. The results of this review did not show significant differences between groups receiving motivational interviewing or usual stroke care for participants who were not dependent on others for activities of daily living, nor on the death rate after three-month and 12-month follow-up, but participants receiving motivational interviewing were more likely to have a normal mood than those who received usual care at three-months and 12-months follow-up. There is insufficient evidence to support the use of motivational interviewing for improving activities of daily living after stroke. Further well designed RCTs are needed.

WHO Parents Skills Training (PST) programme for children with developmental disorders and delays delivered by Family Volunteers in rural Pakistan: study protocol for effectiveness implementation hybrid cluster randomized controlled trial.

PubMed

Hamdani, S U; Akhtar, P; Zill-E-Huma; Nazir, H; Minhas, F A; Sikander, S; Wang, D; Servilli, C; Rahman, A

2017-01-01

Development disorders and delays are recognised as a public health priority and included in the WHO mental health gap action programme (mhGAP). Parents Skills Training (PST) is recommended as a key intervention for such conditions under the WHO mhGAP intervention guide. However, sustainable and scalable delivery of such evidence based interventions remains a challenge. This study aims to evaluate the effectiveness and scaled-up implementation of locally adapted WHO PST programme delivered by family volunteers in rural Pakistan. The study is a two arm single-blind effectiveness implementation-hybrid cluster randomised controlled trial. WHO PST programme will be delivered by 'family volunteers' to the caregivers of children with developmental disorders and delays in community-based settings. The intervention consists of the WHO PST along with the WHO mhGAP intervention for developmental disorders adapted for delivery using the android application on a tablet device. A total of 540 parent-child dyads will be recruited from 30 clusters. The primary outcome is child's functioning, measured by WHO Disability Assessment Schedule - child version (WHODAS-Child) at 6 months post intervention. Secondary outcomes include children's social communication and joint engagement with their caregiver, social emotional well-being, parental health related quality of life, family empowerment and stigmatizing experiences. Mixed method will be used to collect data on implementation outcomes. Trial has been retrospectively registered at ClinicalTrials.gov (NCT02792894). This study addresses implementation challenges in the real world by incorporating evidence-based intervention strategies with social, technological and business innovations. If proven effective, the study will contribute to scaled-up implementation of evidence-based packages for public mental health in low resource settings. Registered with ClinicalTrials.gov as Family Networks (FaNs) for Children with Developmental Disorders and Delays. Identifier: NCT02792894 Registered on 6 July 2016.

Does Oral Implant Design Affect Marginal Bone Loss? Results of a Parallel-Group Randomized Controlled Equivalence Trial

PubMed Central

Bateli, Maria; Ben Rahal, Ghada; Christmann, Marin; Vach, Kirstin; Kohal, Ralf-Joachim

2018-01-01

Objective To test whether or not the modified design of the test implant (intended to increase primary stability) has an equivalent effect on MBL compared to the control. Methods Forty patients were randomly assigned to receive test or control implants to be installed in identically dimensioned bony beds. Implants were radiographically monitored at installation, at prosthetic delivery, and after one year. Treatments were considered equivalent if the 90% confidence interval (CI) for the mean difference (MD) in MBL was in between −0.25 and 0.25 mm. Additionally, several soft tissue parameters and patient-reported outcome measures (PROMs) were evaluated. Linear mixed models were fitted for each patient to assess time effects on response variables. Results Thirty-three patients (21 males, 12 females; 58.2 ± 15.2 years old) with 81 implants (47 test, 34 control) were available for analysis after a mean observation period of 13.9 ± 4.5 months (3 dropouts, 3 missed appointments, and 1 missing file). The adjusted MD in MBL after one year was −0.13 mm (90% CI: −0.46–0.19; test group: −0.49; control group: −0.36; p = 0.507). Conclusion Both implant systems can be considered successful after one year of observation. Concerning MBL in the presented setup, equivalence of the treatments cannot be concluded. Registration This trial is registered with the German Clinical Trials Register (ID: DRKS00007877). PMID:29610765

Training, executive, attention and motor skills (TEAMS) training versus standard treatment for preschool children with attention deficit hyperactivity disorder: a randomised clinical trial.

PubMed

Vibholm, Helle Annette; Pedersen, Jesper; Faltinsen, Erlend; Marcussen, Michael H; Gluud, Christian; Storebø, Ole Jakob

2018-06-08

This study compared the effectiveness of manualised training, executive, attention, and motor skills (TEAMS) training versus standard treatment in preschool children with attention deficit hyperactivity disorder (ADHD). We conducted a randomised parallel group, single-blinded, superiority trial. The primary outcome was ADHD symptoms and the secondary outcome was functionality. Parents and primary school teachers assessed outcomes at pretreatment, posttreatment, and at one, three, and 6 months follow-up. In total, 67 children (aged 3-6 years) were randomised. In the TEAMS group, 32 out of 33 (97%) participants completed the total 8-week program, compared with only 7 out of 26 (27%) in the control group. The repeated-model analyses showed no significant change between the two interventions for ADHD symptoms and functionality levels over time. The mean difference in ADHD symptoms between TEAMS versus standard treatment at posttreatment was 2.18 points (95% confidence interval - 8.62 to 13.0; trial sequential analysis-adjusted confidence interval - 19.3 to 23.7). Trial registration Clinical Trials identifier: NCT01918436 (Retrospectively registered). Registered on 7 August 2013.

Enhancing motivation within a rapid opioid substitution treatment feasibility RCT: a nested qualitative study.

PubMed

Ayres, Rachel; Ingram, Jenny; Rees, Avril; Neale, Jane; Beattie, Angela; Telfer, Maggie

2014-11-18

Opioid substitution treatment (OST) has multiple benefits for heroin injectors and is an evidence-based major component of international treatment. The current qualitative study sought to explore participants' attitudes to and reasons for participating in a feasibility randomised trial in primary care offering 'same day' OST (methadone) for injecting heroin users compared to usual care. Twenty injecting heroin users (8 intervention and 12 controls; 16 males and 4 females) were interviewed; purposive sampling was used to select a maximum variation sample from those who agreed; and analysis used thematic methods. Motivation to join the trial included the need to secure treatment set against some ambivalence due to previous negative experiences of trying to obtain OST. Positive effects of securing methadone via the trial, included self-reported improvements in health and self-care; reduction in crime, stress and drug use. Completing the baseline questionnaires at recruitment appeared to enhance motivation for treatment for all participants. For some control participants, this motivation seemed to increase a sense of self-efficacy and cognitive dissonance generated was resolved by seeking treatment from their GP. Self-determination theory suggests that behaviour change may have been initiated during the recruitment appointment, resulting in an increased determination to seek treatment amongst control participants. Taking part in the 'script in a day' trial enabled participants in the intervention arm to gain same-day access to methadone and reduce their drug use. For those in the control arm, completing the baseline questionnaires at recruitment appeared to create cognitive dissonance between their current health state and own aspirations, so increasing motivation for treatment. Over 50% obtained and were still in receipt of OST (methadone or buprenorphine) at the 3 month follow-up. We suggest that a regular 'health evaluation' for injecting heroin users not in treatment, paired with low-barrier access to treatment, may be a way of exploring this and encouraging more into obtaining OST more quickly and at the best time for them. This intervention should be delivered without pressure for change. This trial is registered with International Standard Randomised Controlled Trial Number Register: SCript In a Day for injecting drug users: feasibility trial: ISRCTN16846554.

Prevalence and factors associated with use of placebo control groups in randomized controlled trials in psoriasis: a cross-sectional study.

PubMed

Katz, Kenneth A; Karlawish, Jason H; Chiang, David S; Bognet, Rachel A; Propert, Katherine J; Margolis, David J

2006-11-01

The ethics and science of using placebo control groups in clinical trials have been widely debated. Few studies, however, have examined factors associated with choice of control group. Our aim was to assess the prevalence of use of placebo controls in randomized controlled trials in psoriasis and to identify factors associated with use of placebo controls in these trials. This is a cross-sectional study of randomized controlled trials in psoriasis published from January 1, 2001 to December 20, 2005 and indexed in the Cochrane Central Register of Controlled Trials. We extracted data on types of control groups used, design issues (number of patients enrolled, primary end point), disease characteristics (psoriasis type and severity), and extrascientific issues (trial location, funding source, and year of publication). We used bivariable and multivariable logistic regression to determine factors associated with use of a placebo control group. Of 194 citations, 187 were available for review. One hundred thirty-five trials from 134 articles in 38 journals met inclusion criteria. Eighty-three trials (61.5%) enrolling 8171 subjects (41.7%) used active controls only, and 52 trials (38.5%) enrolling 11,406 subjects (58.3%) used placebo controls. Adjusted for trial location and funding source, trials significantly more likely to have used placebo controls included those conducted in the United States (odds ratio [OR], 5.79; 95% confidence interval [CI], 2.45-13.68; P < .001) and those funded by pharmaceutical companies (OR, 2.61; 95% CI, 1.19-5.73; P = .02). Predicted frequencies of placebo use ranged from 77.6% (industry-funded, conducted trials in the United States) to 18.6% (non-industry-funded trials not conducted in the United States). Our searches may not have identified all published trials, and we did not have access to data from unpublished trials. Use of placebo controls has been more common in psoriasis trials conducted in the United States and funded by pharmaceutical companies. The findings suggest that ethical and scientific issues related to choice of control group in psoriasis trials are interpreted markedly differently depending on trial location and funding source.

The Benefits of Early Book Sharing (BEBS) for child cognitive and socio-emotional development in South Africa: study protocol for a randomised controlled trial.

PubMed

Dowdall, Nicholas; Cooper, Peter J; Tomlinson, Mark; Skeen, Sarah; Gardner, Frances; Murray, Lynne

2017-03-09

Children in low and middle-income countries (LMICs) are at risk for problems in their cognitive, social and behavioural development. Factors such as a lack of cognitive stimulation, harsh parenting practices, and severe and persistent aggression in early childhood are central to the genesis of these problems. Interventions that target the intersection between early childhood development, parenting, and early violence prevention are required in order to meaningfully address these problems. We are conducting a randomised controlled trial to evaluate a parenting intervention for caregivers of children aged between 23 and 27 months, designed to promote child cognitive and socioemotional development in Khayelitsha, a low-income peri-urban township in South Africa. Families are randomly allocated to a book-sharing intervention group or to a wait-list control group. In the intervention, we train caregivers in supportive book-sharing with young children. Training is carried out in small groups over a period of 8 weeks. Data are collected at baseline, post intervention and at 6 months post intervention. In addition to targeting child cognitive development, the intervention aims to improve child socioemotional functioning. The Benefits of Early Book Sharing (BEBS) trial aims to evaluate the impact of an early parenting intervention on several key risk factors for the development of violence, including aspects of parenting and child cognition, prosocial behaviour, aggression, and socioemotional functioning. The study is being carried out in a LMIC where violence constitutes a major social and health burden. Since the intervention is brief and, with modest levels of training, readily deliverable in LMIC contexts, a demonstration that it is of benefit to both child cognitive and socioemotional development would be of significance. The BEBS trial is registered on the International Standard Randomised Controlled Trial Number database, registration number ISRCTN71109104 . Registered on 9 February 2016. This is version 1 of the protocol for the BEBS trial.

Selective outcome reporting and sponsorship in randomized controlled trials in IVF and ICSI.

PubMed

Braakhekke, M; Scholten, I; Mol, F; Limpens, J; Mol, B W; van der Veen, F

2017-10-01

Are randomized controlled trials (RCTs) on IVF and ICSI subject to selective outcome reporting and is this related to sponsorship? There are inconsistencies, independent from sponsorship, in the reporting of primary outcome measures in the majority of IVF and ICSI trials, indicating selective outcome reporting. RCTs are subject to bias at various levels. Of these biases, selective outcome reporting is particularly relevant to IVF and ICSI trials since there is a wide variety of outcome measures to choose from. An established cause of reporting bias is sponsorship. It is, at present, unknown whether RCTs in IVF/ICSI are subject to selective outcome reporting and whether this is related with sponsorship. We systematically searched RCTs on IVF and ICSI published between January 2009 and March 2016 in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the publisher subset of PubMed. We analysed 415 RCTs. Per included RCT, we extracted data on impact factor of the journal, sample size, power calculation, and trial registry and thereafter data on primary outcome measure, the direction of trial results and sponsorship. Of the 415 identified RCTs, 235 were excluded for our primary analysis, because the sponsorship was not reported. Of the 180 RCTs included in our analysis, 7 trials did not report on any primary outcome measure and 107 of the remaining 173 trials (62%) reported on surrogate primary outcome measures. Of the 114 registered trials, 21 trials (18%) provided primary outcomes in their manuscript that were different from those in the trial registry. This indicates selective outcome reporting. We found no association between selective outcome reporting and sponsorship. We ran additional analyses to include the trials that had not reported sponsorship and found no outcomes that differed from our primary analysis. Since the majority of the trials did not report on sponsorship, there is a risk on sampling bias. IVF and ICSI trials are subject, to a large extent, to selective outcome reporting. Readers should be aware of this to avoid implementation of false or misleading results in clinical practice. No funding received and there are no conflicts of interest. N/A. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Losigamone add-on therapy for partial epilepsy.

PubMed

Xiao, Yousheng; Luo, Man; Wang, Jin; Luo, Hongye

2012-06-13

Epilepsy is a common neurologic disorder, affecting approximately 50 million people worldwide; nearly a third of these people are not well controlled by a single antiepileptic drug and usually require treatment with a combination of two or more antiepileptic drugs. In recent years, many newer antiepileptic drugs have been investigated as add-on therapy for partial epilepsy; losigamone is one of these drugs and is the focus of this systematic review. To investigate the efficacy and safety of losigamone when used as an add-on therapy for partial epilepsy. We searched the Cochrane Epilepsy Group Specialized Register (1 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library, 2012) and MEDLINE (1 May 2012). We searched trials registers and contacted the manufacturer of losigamone and authors of included studies for additional information. There were no language restrictions. Randomized controlled add-on trials comparing losigamone with placebo for partial epilepsy. Two review authors independently assessed trial quality and extracted data. The primary outcomes were 50% or greater reduction in seizure frequency and seizure freedom; the secondary outcomes were treatment withdrawal and adverse events. Results are presented as risk ratios (RR) with 95% confidence intervals (CIs) or 99% CIs (for the individual listed adverse events to make an allowance for multiple testing). Two trials involving a total of 467 patients were eligible for inclusion. Both trials assessed losigamone 1200 or 1500 mg/d as an add-on therapy for partial epilepsy. One trial was assessed as being of good methodologic quality while the other was of uncertain quality. For the efficacy outcomes, results did show patients taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.75; 95% CI 1.14 to 2.72), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16; 95% CI 1.28 to 3.67). For the safety outcomes, results indicated the proportion of patients who experienced adverse events in the losigamone group was higher than the placebo group (RR 1.34; 95% CI 1.00 to 1.80), dizziness was the only adverse event significantly in relation to losigamone (RR 3.82; 99% CI 1.69 to 8.64). The proportion of patients achieving seizure freedom was not reported in either trial report. A subgroup analysis according to different doses of losigamone showed that a higher dose of losigamone (1500 mg/d) is associated with a greater reduction in seizure frequency than lower doses, but is also associated with more dropouts due to adverse events. The results of this review showed losigamone can reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with partial epilepsy. However, trials included were of short-term duration and uncertain quality. Future well-designed randomized, double-blind, placebo-controlled trials with a longer-term duration are needed.

Strategies for improving adherence to antiepileptic drug treatment in people with epilepsy.

PubMed

Al-Aqeel, Sinaa; Gershuni, Olga; Al-Sabhan, Jawza; Hiligsmann, Mickael

2017-02-03

Poor adherence to antiepileptic medication is associated with increased mortality, morbidity and healthcare costs. In this review, we focus on interventions designed and tested in randomised controlled trials and quasi-randomised controlled trials to assist people with adherence to antiepileptic medication. This is an updated version of the original Cochrane review published in the Cochrane Library, Issue 1, 2010. To determine the effectiveness of interventions aimed at improving adherence to antiepileptic medication in adults and children with epilepsy. For the latest update, on 4 February 2016 we searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid 1946 to 4 February 2016), CINAHL Plus (EBSCOhost 1937 to 4 February 2016), PsycINFO (EBSCOhost 1887 to 4 February 2016), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform. We also searched the reference lists of relevant articles. Randomised and quasi-randomised controlled trials of adherence-enhancing interventions aimed at people with a clinical diagnosis of epilepsy (as defined in individual studies), of any age and treated with antiepileptic drugs in a primary care, outpatient or other community setting. All review authors independently assessed lists of potentially relevant citations and abstracts. At least two review authors independently extracted data and performed quality assessment of each study according to the Cochrane tool for assessing risk of bias. We graded the level of evidence for each outcome according to the GRADE working group scale.The studies differed widely according to the type of intervention and measures of adherence; therefore combining data was not appropriate. We included 12 studies reporting data on 1642 participants (intervention = 833, control = 809). Eight studies targeted adults with epilepsy, one study included participants of all ages, one study included participants older than two years, one study targeted caregivers of children with epilepsy, and one study targeted families of children with epilepsy. We identified six ongoing trials. Follow-up time was generally short in most trials, ranging from one to 12 months. The trials examined three main types of interventions: educational interventions, behavioural interventions and mixed interventions. All studies compared treatment versus usual care or 'no intervention', except for two studies. Due to heterogeneity between studies in terms of interventions, methods used to measure adherence and the way the studies were reported, we did not pool the results and these findings were inappropriate to be included in a meta-analysis. Education and counselling of participants with epilepsy resulted in mixed success (moderate-quality evidence). Behavioural interventions such as use of intensive reminders provided more favourable effects on adherence (moderate-quality evidence). The effect on adherence to antiepileptic drugs described by studies of mixed interventions showed improved adherence in the intervention groups compared to the control groups (high-quality evidence). Behavioural interventions such as intensive reminders and the use of mixed interventions demonstrate some positive results; however, we need more reliable evidence on their efficacy, derived from carefully-designed randomised controlled trials before we can draw a firm conclusion. Since the last version of this review, none of the new relevant studies have provided additional information that would lead to significant changes in our conclusions. This current update includes 12 studies, of which six came from the latest searches.

Evaluating a selective prevention program for substance use and comorbid behavioral problems in adolescents with mild to borderline intellectual disabilities: Study protocol of a randomized controlled trial.

PubMed

Schijven, Esmée P; Engels, Rutger C M E; Kleinjan, Marloes; Poelen, Evelien A P

2015-07-22

Substance use and abuse is a growing problem among adolescents with mild to borderline intellectual disabilities (ID). Substance use patterns in general population are similar to patterns among non-disabled peers, but substance use has more negative consequences for adolescents with mild to borderline ID, and they are at an increased risk for developing a substance use disorder. Nevertheless, effective and evidence based prevention programs for this groups are lacking. The study described in this protocol tested the effectiveness of a selective intervention aimed at reducing substance use in adolescents with mild to borderline ID and behavioral problems. In the intervention, participants acquire competences to deal with their high-risk personality traits. A randomized controlled trial will be conducted among 14-21-year old adolescents with mild to borderline ID and behavioral problems admitted to treatment facilities in the Netherlands. Inclusion criteria are previous substance use and personality risk for substance use. Participants will be individually randomized to the intervention (n = 70) or control (n = 70) groups. The intervention group will be exposed to six individual sessions and five group sessions carried out by two qualified trainers over six-week period. Primary outcomes will be the percentage reduction in substance use (for alcohol: percentage decrease of binge drinking, weekly use and problematic use, for cannabis: the percentage decrease of lifetime cannabis use and weekly use and for hard drug: the percentage decrease of lifetime use). Secondary outcomes will be motives for substance use, intention to use, and internalizing and externalizing behavioral problems. All outcome measures will be assessed after two, six, and twelve months after the intervention. This study protocol describes the design of an effectiveness study of a selective prevention program for substance use in adolescents with mild to borderline ID and behavioral problems. We expect a significant reduction in alcohol, cannabis and hard drug use among adolescents in the intervention group compared with the control group. This trial is registered in the Dutch Trial Register (Cochrane Collaboration) as NTR5037 registered at 15 April 2015.

Lack of high-quality studies comparing the effectiveness, and cost-effectiveness, of dental auxiliaries and dentists in performing dental care.

PubMed

Richards, Derek

2015-03-01

Cochrane Effective Practice and Organisation of Care (EPOC) Group's Specialised Register; Cochrane Oral Health Group's Specialised Register; the Cochrane Central Register of Controlled Trials Medline; Embase; CINAHL; Cochrane Database of Systematic Reviews; Database of Abstracts of Reviews of Effectiveness; five other databases and two trial registries. A number of dental journals were hand-searched and a grey literature search preformed. Randomised controlled trials (RCTs), non-randomised controlled trials (NRCTs), controlled before and after studies (CBAs) and interrupted time series (ITSs) were considered. Selection was conducted independently by two reviewers. Three reviewers extracted data and assessed risk of bias. Meta-analysis was not possible so a narrative summary was presented. Four studies evaluated sealant placement; three found no evidence of a difference in retention rates of those placed by dental auxiliaries and dentists over a range of follow-up periods (six to 24 months). One study found that sealants placed by a dental auxiliary had lower retention rates than ones placed by a dentist after 48 months (9.0% with auxiliary versus 29.1% with dentist); but the net reduction in the number of teeth exhibiting caries was lower for teeth treated by the dental auxiliary than the dentist (three with auxiliary versus 60 with dentist, P value < 0.001). One study showed no evidence of a difference in dental decay after treatment with fissure sealants between groups. One study comparing the effectiveness of dental auxiliaries and dentists performing ART reported no difference in survival rates of the restorations (fillings) after 12 months. We only identified five studies for inclusion in this review, all of which were at high risk of bias, and four were published more than 20 years ago, highlighting the paucity of high-quality evaluations of the relative effectiveness, cost-effectiveness and safety of dental auxiliaries compared with dentists in performing clinical tasks. No firm conclusions could be drawn from the present review about the relative effectiveness of dental auxiliaries and dentists.

The At Home/Chez Soi trial protocol: a pragmatic, multi-site, randomised controlled trial of a Housing First intervention for homeless individuals with mental illness in five Canadian cities

PubMed Central

Streiner, David L; Adair, Carol; Aubry, Tim; Barker, Jayne; Distasio, Jino; Hwang, Stephen W; Komaroff, Janina; Latimer, Eric; Somers, Julian; Zabkiewicz, Denise M

2011-01-01

Introduction Housing First is a complex housing and support intervention for homeless individuals with mental health problems. It has a sufficient knowledge base and interest to warrant a test of wide-scale implementation in various settings. This protocol describes the quantitative design of a Canadian five city, $110 million demonstration project and provides the rationale for key scientific decisions. Methods A pragmatic, mixed methods, multi-site field trial of the effectiveness of Housing First in Vancouver, Winnipeg, Toronto, Montreal and Moncton, is randomising approximately 2500 participants, stratified by high and moderate need levels, into intervention and treatment as usual groups. Quantitative outcome measures are being collected over a 2-year period and a qualitative process evaluation is being completed. Primary outcomes are housing stability, social functioning and, for the economic analyses, quality of life. Hierarchical linear modelling is the primary data analytic strategy. Ethics and dissemination Research ethics board approval has been obtained from 11 institutions and a safety and adverse events committee is in place. The results of the multi-site analyses of outcomes at 12 months and 2 years will be reported in a series of core scientific journal papers. Extensive knowledge exchange activities with non-academic audiences will occur throughout the duration of the project. Trial registration number This study has been registered with the International Standard Randomised Control Trial Number Register and assigned ISRCTN42520374. PMID:22102645

Meta-analysis of Prolene Hernia System mesh versus Lichtenstein mesh in open inguinal hernia repair.

PubMed

Sanjay, Pandanaboyana; Watt, David G; Ogston, Simon A; Alijani, Afshin; Windsor, John A

2012-10-01

This study was designed to systematically analyse all published randomized clinical trials comparing the Prolene Hernia System (PHS) mesh and Lichtenstein mesh for open inguinal hernia repair. A literature search was performed using the Cochrane Colorectal Cancer Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase and Science Citation Index Expanded. Randomized trials comparing the Lichtenstein Mesh repair (LMR) with the Prolene Hernia System were included. Statistical analysis was performed using Review Manager Version 5.1 software. The primary outcome measures were hernia recurrence and chronic pain after operation. Secondary outcome measures included surgical time, peri-operative complications, time to return to work, early and long-term postoperative complications. Six randomized clinical trials were identified as suitable, containing 1313 patients. There was no statistical difference between the two types of repair in operation time, time to return to work, incidence of chronic groin pain, hernia recurrence or long-term complications. The PHS group had a higher rate of peri-operative complications, compared to Lichtenstein mesh repair (risk ratio (RR) 0.71, 95% confidence interval 0.55-0.93, P=0.01). The use of PHS mesh was associated with an increased risk of peri-operative complications compared to LMR. Both mesh repair techniques have comparable short- and long-term outcomes. Copyright © 2012 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Home-based exercise and support programme for people with dementia and their caregivers: study protocol of a randomised controlled trial

PubMed Central

2011-01-01

Background Dementia affects the mood of people with dementia but also of their caregivers. In the coming years, the number of people with dementia will increase worldwide and most of them will continue to live in the community as long as possible. Home-based psychosocial interventions reducing the depressive symptoms of both people with dementia and their caregivers in their own home are highly needed. Methods/Design This manuscript describes the design of a Randomised Controlled Trial (RCT) of the effects of a home-based exercise and support programme for people with dementia and their caregivers. The aim is to randomly assign 156 dyads (caregiver and dementia diagnosed person) to an intervention group or a comparison group. The experimental group receives a home programme in which exercise and support for the people with dementia and their caregivers are combined and integrated. The comparison group receives a minimal intervention. Primary outcomes are physical health (people with dementia) and mood (people with dementia and caregivers). In addition, to get more insight in the working components of the intervention and the impact of the intervention on the relationship of the dyads a qualitative sub-study is carried out. Discussion This study aims to contribute to an evidence-based treatment to reduce depressive symptoms among people with dementia and their caregivers independently living in the community. Trial Registration The study has been registered at the Netherlands National Trial Register (NTR), which is connected to the International Clinical Trials Registry Platform of the WHO. Trial number: NTR1802. PMID:22117691

Interventions for suspected placenta praevia.

PubMed

Neilson, J P

2000-01-01

Because placenta praevia is implanted unusually low in the uterus, it may cause major, and/or repeated, antepartum haemorrhage. The traditional policy of care of women with symptomatic placenta praevia includes prolonged stay in hospital and delivery by caesarean section. To assess the impact of any clinical intervention applied specifically because of a perceived likelihood that a pregnant woman might have placenta praevia. A comprehensive electronic search was performed to identify relevant literature. Searched databases included the Trials Register maintained by the Cochrane Pregnancy and Childbirth Group, and the Cochrane Controlled Clinical Trials Register. Any controlled clinical trial that has assessed the impact of an intervention in women diagnosed as having, or being likely to have, placenta praevia. Data were extracted from the three identified trial reports, unblinded, by the author without consideration of results. Two comparisons could be made - home versus hospitalisation and cervical cerclage versus no cerclage. Both were associated with reduced lengths of stay in hospital antenatally. Otherwise, there was little evidence of any clear advantage or disadvantage to a policy of home versus hospital care. Cervical cerclage may reduce the risk of delivery before 34 weeks, or the birth of a baby weighing less than 2 kg or having a low 5 minute Apgar score. In general, these possible benefits were more evident in the trial of lesser methodological quality. There are insufficient data from trials to recommend any change in clinical practice. Available data should, however, should encourage further work to address the safety of more conservative policies of hospitalisation for women with suspected placenta praevia, and the possible value of insertion of a cervical suture.

Recruitment of older adults to three preventative lifestyle improvement studies.

PubMed

Chatters, Robin; Newbould, Louise; Sprange, Kirsty; Hind, Daniel; Mountain, Gail; Shortland, Katy; Powell, Lauren; Gossage-Worrall, Rebecca; Chater, Tim; Keetharuth, Anju; Lee, Ellen; Woods, Bob

2018-02-20

Recruiting isolated older adults to clinical trials is complex, time-consuming and difficult. Previous studies have suggested querying existing databases to identify appropriate potential participants. We aim to compare recruitment techniques (general practitioner (GP) mail-outs, community engagement and clinician referrals) used in three randomised controlled trial (RCT) studies assessing the feasibility or effectiveness of two preventative interventions in isolated older adults (the Lifestyle Matters and Putting Life In Years interventions). During the three studies (the Lifestyle Matters feasibility study, the Lifestyle Matters RCT, the Putting Life In Years RCT) data were collected about how participants were recruited. The number of letters sent by GP surgeries for each study was recorded. In the Lifestyle Matters RCT, we qualitatively interviewed participants and intervention facilitators at 6 months post randomisation to seek their thoughts on the recruitment process. Referrals were planned to be the main source of recruitment in the Lifestyle Matters feasibility study, but due to a lack of engagement from district nurses, community engagement was the main source of recruitment. District nurse referrals and community engagement were also utilised in the Lifestyle Matters and Putting Life In Years RCTs; both mechanisms yielded few participants. GP mail-outs were the main source of recruitment in both the RCTs, but of those contacted, recruiting yield was low (< 3%). Facilitators of the Lifestyle Matters intervention questioned whether the most appropriate individuals had been recruited. Participants recommended that direct contact with health professionals would be the most beneficial way to recruit. Recruitment to the Lifestyle Matters RCT did not mirror recruitment to the feasibility study of the same intervention. Direct district nurse referrals were not effective at recruiting participants. The majority of participants were recruited via GP mail-outs, which may have led to isolated individuals not being recruited to the trials. Further research is required into alternative recruitment techniques, including respondent-driven sampling plus mechanisms which will promote health care professionals to recruit vulnerable populations to research. International Standard Randomised Controlled Trial Registry, ID: ISRCTN28645428 (Putting Life In Years RCT). Registered on 11 April 2012; International Standard Randomised Controlled Trial Registry, ID: ISRCTN67209155 (Lifestyle Matters RCT). Registered on 22 March 2012; ClinicalTrials.gov , ID: NCT03054311 (Lifestyle Matters feasibility study). Registered retrospectively on 19 January 2017.

Infection control strategies for preventing the transmission of meticillin-resistant Staphylococcus aureus (MRSA) in nursing homes for older people.

PubMed

Hughes, Carmel; Smith, Michael; Tunney, Michael; Bradley, Marie C

2011-12-07

Nursing homes for older people provide an environment likely to promote the acquisition and spread of meticillin-resistant Staphylococcus aureus (MRSA), putting residents at increased risk of colonisation and infection. It is recognised that infection prevention and control strategies are important in preventing and controlling MRSA transmission. To determine the effects of infection prevention and control strategies for preventing the transmission of MRSA in nursing homes for older people. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2011, Issue 2), the Cochrane Wounds Group Specialised Register (searched May 27th, 2011). We also searched Ovid MEDLINE (from 1950 to April Week 2 2011), OVID MEDLINE (In-process and Other Non-Indexed Citations, April 26th 2011) Ovid EMBASE (1980 to 2011 Week 16), EBSCO CINAHL (1982 to April 21st 2011), DARE (1992 to 2011, week 16), Web of Science (1981 to May 2011), and the Health Technology Assessment (HTA) website (1988 to May 2011). Research in progress was sought through Current Clinical Trials (www.controlled-trials.com), Medical Research Council Research portfolio, and HSRPRoj (current USA projects). All randomised and controlled clinical trials, controlled before and after studies and interrupted time series studies of infection prevention and control interventions in nursing homes for older people were eligible for inclusion. Two review authors independently reviewed the results of the searches. Another review author appraised identified papers and undertook data extraction which was checked by a second review author. For this second update only one study was identified, therefore it was not possible to undertake a meta-analysis. A cluster randomised controlled trial in 32 nursing homes evaluated the effect of an infection control education and training programme on MRSA prevalence. The primary outcome was MRSA prevalence in residents and staff, and a change in infection control audit scores which measured adherence to infection control standards. At the end of the 12 month study, there was no change in MRSA prevalence between intervention and control sites, while mean infection control audit scores were significantly higher in the intervention homes compared with control homes. There is a lack of research evaluating the effects on MRSA transmission of infection prevention and control strategies in nursing homes. Rigorous studies should be conducted in nursing homes, to test interventions that have been specifically designed for this unique environment.

Clinical trials in dentistry in India: Analysis from trial registry.

PubMed

Gowri, S; Kannan, Sridharan

2017-01-01

Evidence-based practice requires clinical trials to be performed. In India, if any clinical trial has to be performed, it has to be registered with clinical trial registry of India. Studies have shown that the report of clinical trials is poor in dentistry. Hence, the present study has been conducted to assess the type and trends of clinical trials being undertaken in dentistry in India over a span of 6 years. All the clinical trials which were registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental." Following information were collected for each of the clinical trials obtained from the search; number of centres (single center/multicentric), type of the institution undertaking the research (government/private/combined), study (observational/interventional), study design (randomized/single blinded/double-blinded), type of health condition, type of participants (healthy/patients), sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4), publication details (published/not published), whether it was a postgraduate thesis or not and prospective or retrospective registration of clinical trials, methodological quality (method of randomization, allocation concealment). Descriptive statistics was used for analysis of various categories. Trend analysis was done to assess the changes over a period of time. The search yielded a total of 84 trials of which majority of them were single centered. Considering the study design more than half of the registered clinical trials were double-blinded (47/84 [56%]). With regard to the place of conducting a trial, most of the trials were planned to be performed in private hospitals (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the registered clinical trials were recruiting patients while the rest were being done in healthy participants. From 2011, some of the postgraduate thesis trials had also been registered (2011-8; 2012-8; 2013-13; 2014-6). Inadequacy in reporting the method of randomization and allocation concealment was observed in 37/67 (55.2%) and 31/67 (46.2%) clinical trials respectively. A considerable number of postgraduate theses was also registered with CTRI in dentistry and majority of the clinical trials despite being completed are not yet published. The number of clinical trials in dentistry are low in India, and more focus should be placed by dental investigators regarding the reporting standards. Furthermore, researchers and trial sponsors should aim at publication of the research findings so that it is made publically available for use. A clear-cut need exists for an increase in both the quantity and quality of clinical trials in dentistry.

Enteral tube feeding for cystic fibrosis.

PubMed

Conway, S P; Morton, A; Wolfe, S

2008-04-16

Enteral tube feeding is routinely used in many cystic fibrosis centres when weight for height percentage is less than 85%, when there has been weight loss for longer than a two-month period or when there has been no weight gain for two to three months (under five years old) or for six months (over five years old). To examine the evidence that in people with cystic fibrosis supplemental enteral tube feeding improves nutritional status, respiratory function, and quality of life without significant adverse effects. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also contacted the companies that market enteral feeds and reviewed their databases. Date of the most recent search of the Group's Cystic Fibrosis Trials Register: November 2007. All randomised controlled trials comparing supplemental enteral tube feeding for one month or longer with no specific intervention in people with cystic fibrosis. Thirteen trials were identified by the search; however, none were eligible for inclusion in this review. There are no trials included in this review. Supplemental enteral tube feeding is widely used throughout the world to improve nutritional status in people with cystic fibrosis. The methods mostly used, nasogastric or gastrostomy feeding, are invasive, expensive, and may have a negative effect on self-esteem and body image. Reported use of enteral tube feeding suggests that it results in nutritional and respiratory improvement and it is disappointing that their efficacy has not been fully assessed by randomised controlled trials. With the more frequent recommendations to use enteral tube feeding as an early rather than a late intervention, this systematic review identifies the need for a multicentre, randomised controlled trial assessing both efficacy and possible adverse effects of enteral tube feeding in cystic fibrosis. There are no trials included in the review and we have not identified any relevant trials up to November 2007. We therefore do not plan to update this review until new trials are published.

Benzodiazepines for delirium.

PubMed

Lonergan, Edmund; Luxenberg, Jay; Areosa Sastre, Almudena

2009-10-07

Delirium occurs in 30% of hospitalised patients and is associated with prolonged hospital stay and increased morbidity and mortality. The results of uncontrolled studies have been unclear, with some suggesting that benzodiazepines may be useful in controlling non-alcohol related delirium. To determine the effectiveness and incidence of adverse effects of benzodiazapines in the treatment of non-alcohol withdrawal related delirium. The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 26 February 2008 using the search terms: (deliri* or confusion) and (benzo* or lorazepam," or "alprazolam" or "ativan" or diazepam or valium or chlordiazepam).The CDCIG Specialized Register contains records from major health databases (including MEDLINE, EMBASE, CINAHL, PsycINFO, CENTRAL, LILACS) as well as many ongoing trial databases and grey literature sources. Trials had to be unconfounded, randomized and with concealed allocation of subjects. Additionally, selected trials had to have assessed patients pre- and post-treatment. Where crossover design was present, only data from the first part of the trial were to be examined. Two reviewers extracted data from included trials. Data were pooled where possible, and were to be analysed using appropriate statistical methods. Odd ratios or average differences were to be calculated. Only "intention to treat" data were to be included. Only one trial satisfying the selection criteria could be identified. In this trial, comparing the effect of the benzodiazepine, lorazepam, with dexmedetomidine, a selective alpha-2-adrenergic receptor agonist, on delirium among mechanically ventilated intensive care unit patients, dexmedetomidine treatment was associated with an increased number of delirium- and coma-free days compared with lorazepam treated patients (dexmedetomidine patients, average seven days; lorazepam patients, average three days; P = 0.01). One partially controlled study showed no advantage of a benzodiazepine (alprazolam) compared with neuroleptics in treating agitation associated with delirium, and another partially controlled study showed decreased effectiveness of a benzodiazepine (lorazepam), and increased adverse effects, compared with neuroleptics (haloperidol, chlorpromazine) for the treatment of acute confusion. No adequately controlled trials could be found to support the use of benzodiazepines in the treatment of non-alcohol withdrawal related delirium among hospitalised patients, and at this time benzodiazepines cannot be recommended for the control of this condition. Because of the scarcity of trials with randomization of patients, placebo control, and adequate concealment of allocation of subjects, it is clear that further research is required to determine the role of benzodiazepines in the treatment of non-alcohol withdrawal related delirium.

Benzodiazepines for delirium.

PubMed

Lonergan, Edmund; Luxenberg, Jay; Areosa Sastre, Almudena; Wyller, Torgeir Bruun

2009-01-21

Delirium occurs in 30% of hospitalised patients and is associated with prolonged hospital stay and increased morbidity and mortality. The results of uncontrolled studies have been unclear, with some suggesting that benzodiazepines may be useful in controlling non-alcohol related delirium. To determine the effectiveness and incidence of adverse effects of benzodiazapines in the treatment of non-alcohol withdrawal related delirium. The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 26 February 2008 using the search terms: (deliri* or confusion) and (benzo* or lorazepam," or "alprazolam" or "ativan" or diazepam or valium or chlordiazepam).The CDCIG Specialized Register contains records from major health databases (including MEDLINE, EMBASE, CINAHL, PsycINFO, CENTRAL, LILACS) as well as many ongoing trial databases and grey literature sources. Trials had to be unconfounded, randomized and with concealed allocation of subjects. Additionally, selected trials had to have assessed patients pre- and post-treatment. Where crossover design was present, only data from the first part of the trial were to be examined. Two reviewers extracted data from included trials. Data were pooled where possible, and were to be analysed using appropriate statistical methods. Odd ratios or average differences were to be calculated. Only "intention to treat" data were to be included. Only one trial satisfying the selection criteria could be identified. In this trial, comparing the effect of the benzodiazepine, lorazepam, with dexmedetomidine, a selective alpha-2-adrenergic receptor agonist, on delirium among mechanically ventilated intensive care unit patients, dexmedetomidine treatment was associated with an increased number of delirium- and coma-free days compared with lorazepam treated patients (dexmedetomidine patients, average seven days; lorazepam patients, average three days; P = 0.01). One partially controlled study showed no advantage of a benzodiazepine (alprazolam) compared with neuroleptics in treating agitation associated with delirium, and another partially controlled study showed decreased effectiveness of a benzodiazepine (lorazepam), and increased adverse effects, compared with neuroleptics (haloperidol, chlorpromazine) for the treatment of acute confusion. No adequately controlled trials could be found to support the use of benzodiazepines in the treatment of non-alcohol withdrawal related delirium among hospitalised patients, and at this time benzodiazepines cannot be recommended for the control of this condition. Because of the scarcity of trials with randomization of patients, placebo control, and adequate concealment of allocation of subjects, it is clear that further research is required to determine the role of benzodiazepines in the treatment of non-alcohol withdrawal related delirium.

Clinical significance of tumor necrosis factor-α inhibitors in the treatment of sciatica: a systematic review and meta-analysis.

PubMed

Wang, Yun Fu; Chen, Ping You; Chang, Wei; Zhu, Fi Qi; Xu, Li Li; Wang, Song Lin; Chang, Li Ying; Luo, Jie; Liu, Guang Jian

2014-01-01

Currently, no satisfactory treatment is available for sciatica caused by herniated discs and/or spinal stenosis. The objective of this study is to assess the value of tumor necrosis factor (TNF)-α inhibitors in the treatment of sciatica. Without language restrictions, we searched PubMed, OVID, EMBASE, the Web of Science, the Clinical Trials Registers, the Cochrane Central Register of Controlled Trials and the China Academic Library and Information System. We then performed a systematic review and meta-analysis on the enrolled trials that met the inclusion criteria. Nine prospective randomized controlled trials (RCTs) and two before-after controlled trials involving 531 patients met our inclusion criteria and were included in this study. Our systematic assessment and meta-analysis demonstrated that in terms of the natural course of the disease, compared with the control condition, TNF-α inhibitors neither significantly relieved lower back and leg pain (both p > 0.05) nor enhanced the proportion of patients who felt overall satisfaction (global perceived effect (satisfaction)) or were able to return to work (return to work) (combined endpoint; p > 0.05) at the short-term, medium-term and long-term follow-ups. In addition, compared with the control condition, TNF-α inhibitors could reduce the risk ratio (RR) of discectomy or radicular block (combined endpoint; RR = 0.51, 95% CI 0.26 to 1.00, p = 0.049) at medium-term follow-up, but did not decrease RR at the short-term (RR = 0.64, 95% CI 0.17 to 2.40, p = 0.508) and long-term follow-ups (RR = 0.64, 95% CI 0.40 to 1.03, p = 0.065). The currently available evidence demonstrated that other than reducing the RR of discectomy or radicular block (combined endpoint) at medium-term follow-up, TNF-α inhibitors showed limited clinical value in the treatment of sciatica caused by herniated discs and/or spinal stenosis.

Internet-delivered cognitive behaviour therapy for depression in people with diabetes: study protocol for a randomised controlled trial

PubMed Central

Robins, Lisa; Newby, Jill; Wilhelm, Kay; Smith, Jessica; Fletcher, Therese; Ma, Trevor; Finch, Adam; Campbell, Lesley; Andrews, Gavin

2015-01-01

Introduction Depression substantially contributes to the personal burden and healthcare costs of living with diabetes mellitus (DM). Comorbid depression and DM are associated with poorer quality of life, poorer self-management and glycemic control, increased risk for DM complications and higher mortality rates, and higher health service utilization. Depression remains under-recognized and undertreated in people with DM, which may, in part, result from barriers associated with accessing face-to-face treatment. This study will examine the efficacy of an internet-based cognitive behaviour therapy programme for major depressive disorder (iCBT-MDD) in people with DM. Methods and analysis A CONSORT 2010 compliant, registered randomised controlled trial of the intervention (iCBT-MDD) versus a treatment as usual control group will be conducted. The study will include 100 adults aged 18 years and over with a diagnosis of type 1 or type 2 DM and self-reported symptoms that satisfy MDD which will enable us to detect a statistically significant difference with a group effect size of 0.6 at a power of 80% and significance level of p=0.05. Participants will be randomised to receive the iCBT-MDD programme immediately, or to wait 10 weeks before accessing the programme. Primary outcomes will be self-reported depression severity, DM-related distress, and glycemic control (glycosylated hemoglobin). Secondary outcomes will be general distress and disability, generalized anxiety, lifestyle behaviours, somatization, eating habits, alcohol use, and acceptability of the iCBT programme to participants, and practicality for clinicians. Data will be analyzed with linear mixed models for each outcome measure. Ethics and dissemination The Human Research Ethics Committee of St Vincent's Hospital Australia have given ethics approval (HREC/13/SVH/291). Results will be disseminated via peer-reviewed publication and social media channels of Australian Diabetes Consumer Representative Bodies. Trial registration number The trial is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12613001198718). PMID:26688735

The effectiveness of delegation interventions by the registered nurse to the unlicensed assistive personnel and their impact on quality of care, patient satisfaction, and RN staff satisfaction: a systematic review.

PubMed

Hopkins, Una; Itty, Any Sajan; Nazario, Helen; Pinon, Miriam; Slyer, Jason; Singleton, Joanne

Delegation by the registered nurse is a decision making process that includes assessment, planning, implementation, and evaluation. Due to an ever-expanding global shortage of nurses, registered nurses are increasingly dependent on unlicensed assistive personnel to assist in the provision of safe patient care. Delegation is recognised as a fundamental nursing skill that can be utilised effectively to improve quality care. To examine and synthesize the best available evidence regarding the impact of delegation interventions used by the registered nurse with the unlicensed assistive personnel and their impact on quality of care, patient satisfaction, and registered nurse staff satisfaction. Registered nurses and unlicensed assistive personnel in patient care settings where delegation occurs.This review considered studies that evaluated the effectiveness of delegation interventions by registered nurses to unlicensed assistive personnel.The outcomes examined were quality of care, patient satisfaction, and/or registered nurse staff satisfaction as measured by validated and reliable tools.The review first considered randomised controlled trials; in their absence other research designs, such as non-randomised controlled trials, or other quasi-experimental studies, observational studies and descriptive studies were considered for inclusion in the systematic review. The search strategy aimed to find both published and unpublished studies in the English language from the inception of the included databases through December 2011. The databases searched included the Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, CINAHL, Healthsource Nursing/Academic edition, and PsycINFO. A search of the grey literature and electronic hand searching of relevant journals was also performed. The studies selected for retrieval were critically evaluated by two independent reviewers for methodological quality using standardised critical appraisal instruments from the Joanna Briggs Institute. Data were extracted using standardised data extraction instruments from the Joanna Briggs Institute. Studies were found to have significant heterogeneity between the populations and interventions of the included studies; therefore, pooled statistical meta-analysis could not be completed. The findings are presented in narrative form. Two quasi-experimental studies were identified. In one study, the women counselled by the lay nurse aides received 80% of recommended messages compared to 75% received by the women counselled by the nurse-midwives (β= 4.7, 95%CI: -1.7, 11.0; Non-inferiority). Non-inferiority was demonstrated between the lay nurse aides and the nurse-midwives with respect to communication techniques. The mean performance was high, 95% and 98% among nurse-midwives and lay nurse aides respectively (β =2.4, 95%CI: -0.2, 5.0; Non-inferiority). No difference was found between the nurse-midwives and the lay nurse aides in providing antenatal counselling, education, and maternal-newborn care when proper training and supervision was given. The other study examined six hypotheses that looked at quality of care outcomes in a care model where the registered nurse delegated tasks to unlicensed assistive personal. Five of these outcomes showed no significant improvement as a result of the intervention. Patient knowledge about intravenous therapy was the only quality of care outcome that showed improvement post-intervention with scores increasing from 27% at baseline to 78% at 12 months. There was no improvement in the one hypotheses evaluating registered nurses job satisfaction. There is a paucity of evidence on the effectiveness of delegation interventions and strategies by registered nurses to unlicensed assistive personnel. Delegation interventions require characteristics such as teamwork, training, support, supervision, communication, and evaluation to positively impact quality of care, patient satisfaction, and registered nurse staff satisfaction outcomes. Task shifting could have a positive impact on quality of care and staff satisfaction while providing the registered nurse with an opportunity to increase efficiency. The areas of feedback and evaluation in the registered nurse / unlicensed assistive personnel relationship needs further study.

Clinical trials in peripheral vascular disease: pipeline and trial designs: an evaluation of the ClinicalTrials.gov database.

PubMed

Subherwal, Sumeet; Patel, Manesh R; Chiswell, Karen; Tidemann-Miller, Beth A; Jones, W Schuyler; Conte, Michael S; White, Christopher J; Bhatt, Deepak L; Laird, John R; Hiatt, William R; Tasneem, Asba; Califf, Robert M

2014-11-11

Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); until recently, however, it has not been possible to examine the entire clinical trial portfolio of studies for the treatment of PVD (both arterial and venous disease). We examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40,970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower-extremity peripheral artery disease and acute stroke (35% and 24%, respectively), whereas most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients >65 years of age. Enrollment in at least 1 US site decreased from 51% of trials in 2007 to 41% in 2010. Compared with noncardiology disciplines, PVD trials were more likely to be double-blinded, to investigate the use of devices and procedures, and to have industry sponsorship and assumed funding source, and they were less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas. PVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD. © 2014 American Heart Association, Inc.

Antibiotics for preventing recurrent sore throat.

PubMed

Ng, Gareth J Y; Tan, Stephanie; Vu, Anh N; Del Mar, Chris B; van Driel, Mieke L

2015-07-14

Antibiotics are sometimes used to prevent recurrent sore throat, despite concern about resistance. However, there is conflicting primary evidence regarding their effectiveness. To assess the effects of antibiotics in patients with recurrent sore throat. The Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator searched the CENTDG Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 5); PubMed; EMBASE; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 25 June 2015. Randomised controlled trials (RCTs) of antibiotics in adults and children suffering from pre-existing recurrent sore throat, defined as three or more sore throats in a year, examining the incidence of sore throat recurrence, with follow-up of at least 12 months post-antibiotic therapy. Two authors independently assessed trial quality and extracted data. Multiple attempts to contact the authors of one study yielded no response. We identified no trials that met the inclusion criteria for the review. We discarded the majority of the references retrieved from our search following screening of the title and abstract. We formally excluded four studies following review of the full-text report. There is insufficient evidence to determine the effectiveness of antibiotics for preventing recurrent sore throat. This finding must be balanced against the known adverse effects and cost of antibiotic therapy, when considering antibiotics for this purpose. There is a need for high quality RCTs that compare the effects of antibiotics versus placebo in adults and children with pre-existing recurrent sore throat on the following outcomes: incidence of sore throat recurrence, adverse effects, days off work and absence from school, and the incidence of complications. Future studies should be conducted and reported according to the CONSORT statement.

Duration of treatment for asymptomatic bacteriuria during pregnancy.

PubMed

Villar, J; Lydon-Rochelle, M T; Gülmezoglu, A M; Roganti, A

2000-01-01

A Cochrane systematic review has shown that drug treatment of asymptomatic bacteriuria in pregnant women substantially decreases the risk of pyelonephritis and reduces the risk of preterm delivery. However, it is not clear whether single dose therapy is as effective as longer conventional antibiotic treatment. The objective of this review was to assess the effects of different durations of treatment for asymptomatic bacteriuria in pregnancy. We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and the reference lists of articles. Randomised and quasi-randomised trials comparing antimicrobial therapeutic regimens that differed in duration (particularly comparing single dose with longer duration regimens) in pregnant women diagnosed with asymptomatic bacteriuria. Trial quality was assessed and data were extracted independently by the reviewers. Eight studies involving over 400 women were included. All were comparisons of single dose treatment with four to seven day treatments. The trials were generally of poor quality. No difference in 'no-cure' rate was detected between single dose and short course (4-7 day) treatment for asymptomatic bacteriuria in pregnant women (relative risk 1.13, 95% confidence interval 0.82 to 1.54) as well as in the recurrent asymptomtic bacteriuria (relative risk 1.08, 95% confidence interval 0.70 to 1.66). However these results showed significant heterogeneity. No differences were detected for preterm births and pyelonephritis although sample size of trials was small. Longer duration treatment was associated with an increase in reports of adverse effects (relative risk 0.53, 95% confidence interval 0.31 to 0.91). There is not enough evidence to evaluate whether single dose or longer duration doses are more effective in treating asymptomatic bacteriuria in pregnant women. Because single dose has lower cost and increases compliance, this comparison should be explored in a properly sized randomized controlled trial.

A feasibility study investigating the acceptability and design of a multicentre randomised controlled trial of needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren's contractures of the fingers (HAND-1): study protocol for a randomised controlled trial.

PubMed

Harrison, Eleanor; Tan, Wei; Mills, Nicola; Karantana, Alexia; Sprange, Kirsty; Duley, Lelia; Elliott, Daisy; Blazeby, Jane; Hollingworth, William; Montgomery, Alan A; Davis, Tim

2017-08-25

Dupuytren's contractures are fibrous cords under the skin of the palm of the hand. The contractures are painless but cause one or more fingers to curl into the palm, resulting in loss of function. Standard treatment within the NHS is surgery to remove (fasciectomy) or divide (fasciotomy) the contractures, and the treatment offered is frequently determined by surgeon preference. This study aims to determine the feasibility of conducting a large, multicentre randomised controlled trial to assess the clinical and cost-effectiveness of needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren's contracture. HAND-1 is a parallel, two-arm, multicentre, randomised feasibility trial. Eligible patients aged 18 years or over who have one or more fingers with a Dupuytren's contracture of more than 30° in the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints, well-defined cord(s) causing contracture, and have not undergone previous surgery for Dupuytren's on the same hand will be randomised (1:1) to treatment with either needle fasciotomy or limited fasciectomy. Participants will be followed-up for up to 6 months post surgery. Feasibility outcomes include number of patients screened, consented and randomised, adherence with treatment, completion of follow-up and identification of an appropriate patient-reported outcome measure (PROM) to use as primary outcome for a main trial. Embedded qualitative research, incorporating a QuinteT Recruitment Intervention, will focus on understanding and optimising the recruitment process, and exploring patients' experiences of trial participation and the interventions. This study will assess whether a large multicentre trial comparing the clinical and cost-effectiveness of needle fasciotomy and limited fasciectomy for the treatment of Dupuytren's contractures is feasible, and if so will provide data to inform its design and successful conduct. International Standard Registered Clinical/soCial sTudy Number: ISRCTN11164292 . Registered on 28 August 2015.

Dissipation and transport of clopyralid in soil: Effect of application strategies

USDA-ARS?s Scientific Manuscript database

At present there are no herbicides registered for broadleaf weed control in buckwheat. Clopyralid, mixed with desmedipham, was anticipated to provide early-season broadleaf weed suppression with minimal crop injury. However, field trials resulted in limited success which brought to question the fate...

Aloe vera herbal dentifrices for plaque and gingivitis control: a systematic review.

PubMed

Dhingra, K

2014-04-01

To evaluate the effectiveness of aloe vera containing herbal dentifrices in improving plaque control and gingival health. A manual and electronic literature (MEDLINE and Cochrane Central Register of Controlled Trials) search was performed up to July 2012, for randomized controlled trials presenting clinical, microbiological, immunological, and patient-centered data for the efficacy of aloe vera herbal dentifrices for controlling plaque and gingival inflammation in patients with gingivitis. From 79 titles and abstracts, eight full-text articles were screened and finally two randomized controlled trials were selected. These randomized controlled trials reported that aloe vera dentifrices were similar in efficacy to control dentifrices in effectively reducing plaque and gingival inflammation in gingivitis patients based on the assessment of clinical, microbiological, and patient-centered treatment outcomes. However, many important details (composition and characteristics of aloe vera and control dentifrices along with appropriate randomization, blinding, and outcomes assessed) were lacking in these trials, and therefore, the quality of reporting and methods was generally flawed with high risk of bias. Even though there are some promising results, the clinical effectiveness of aloe vera herbal dentifrices is not sufficiently defined at present and warrants further investigations based on reporting guidelines of herbal CONSORT statement. © 2013 John Wiley & Sons A/S.

The Effect of Adjuvant Zinc Therapy on Recovery from Pneumonia in Hospitalized Children: A Double-Blind Randomized Controlled Trial

PubMed Central

Qasemzadeh, Mohammad Javad; Fathi, Mahdi; Tashvighi, Maryam; Gharehbeglou, Mohammad; Yadollah-Damavandi, Soheila; Parsa, Yekta; Rahimi, Ebrahim

2014-01-01

Objectives. Pneumonia is one of the common mortality causes in young children. Some studies have shown beneficial effect of zinc supplements on treatment of pneumonia. The present study aimed to investigate the effects of short courses of zinc administration on recovery from this disease in hospitalized children. Methods. In a parallel Double-Blind Randomized Controlled Trial at Ayatollah Golpaygani Hospital in Qom, 120 children aged 3–60 months with pneumonia were randomly assigned 1 : 1 to receive zinc or placebo (5 mL every 12 hours) along with the common antibiotic treatments until discharge. Primary outcome was recovery from pneumonia which included the incidence and resolving clinical symptoms and duration of hospitalization. Results. The difference between two groups in all clinical symptoms at admittance and the variables affecting the disease such as age and sex were not statistically significant (P < 0.05) at baseline. Compared to the placebo group, the treatment group showed a statistically significant decrease in duration of clinical symptoms (P = 0.044) and hospitalization (P = 0.004). Conclusions. Supplemental administration of zinc can expedite the healing process and results in faster resolution of clinical symptoms in children with pneumonia. In general, zinc administration, along with common antibiotic treatments, is recommended in this group of children. It can also reduce the drug resistance caused by multiple antibiotic therapies. This trial is approved by Medical Ethic Committee of Islamic Azad University in Iran (ID Number: 8579622-Q). This study is also registered in AEARCTR (The American Economic Association's Registry for Randomized Controlled Trials). This trial is registered with RCT ID: AEARCTR-0000187. PMID:24955282

Physiotherapy treatment approaches for the recovery of postural control and lower limb function following stroke.

PubMed

Pollock, A; Baer, G; Pomeroy, V; Langhorne, P

2007-01-24

There are a number of different approaches to physiotherapy treatment following stroke that, broadly speaking, are based on neurophysiological, motor learning and orthopaedic principles. Some physiotherapists base their treatment on a single approach, while others use a mixture of components from a number of different approaches. To determine if there is a difference in the recovery of postural control and lower limb function in patients with stroke if physiotherapy treatment is based on orthopaedic or neurophysiological or motor learning principles, or on a mixture of these treatment principles. We searched the Cochrane Stroke Group Trials Register (last searched May 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to May 2005), EMBASE (1980 to May 2005) and CINAHL (1982 to May 2005). We contacted experts and researchers with an interest in stroke rehabilitation. Randomised or quasi-randomised controlled trials of physiotherapy treatment approaches aimed at promoting the recovery of postural control and lower limb function in adult participants with a clinical diagnosis of stroke. Outcomes included measures of disability, motor impairment or participation. Two review authors independently categorised the identified trials according to the inclusion and exclusion criteria, documented their methodological quality, and extracted the data. Twenty-one trials were included in the review, five of which were included in two comparisons. Eight trials compared a neurophysiological approach with another approach; eight compared a motor learning approach with another approach; and eight compared a mixed approach with another approach. A mixed approach was significantly more effective than no treatment or placebo control for improving functional independence (standardised mean difference (SMD) 0.94, 95% confidence intervals (CI) 0.08 to 1.80). There was no significant evidence that any single approach had a better outcome than any other single approach or no treatment control. There is evidence that physiotherapy intervention, using a mix of components from different approaches, is significantly more effective than no treatment or placebo control in the recovery of functional independence following stroke. There is insufficient evidence to conclude that any one physiotherapy approach is more effective in promoting recovery of lower limb function or postural control following stroke than any other approach. We recommend that future research should concentrate on investigating the effectiveness of clearly described individual techniques and task-specific treatments, regardless of their historical or philsophical origin.

Brazilian medicinal plants to treat upper respiratory tract and bronchial illness: systematic review and meta-analyses—study protocol

PubMed Central

Lopes, Luciane C; Silva, Maria Carolina O; Motta, Cristiane Bergamashi; Macho Quirós, Antonio; Biavatti, Maique Weber; de Oliveira, Jardel Corrêa; Guyatt, Gordon

2014-01-01

Introduction Respiratory illness, often associated with cough and sputum, is frequent. In Brazil, herbal medicines are often recommended as a first-line treatment for respiratory illness. There exists uncertainty regarding the effectiveness of these treatments. No systematic review has evaluated Brazilian medicinal plants (BMP) to treat upper respiratory tract and bronchial illness (URTI). Methods and analysis We will conduct a systematic review and, if appropriate, a series of meta-analyses evaluating the safety and effectiveness of BMP for URTI. Eligible randomised controlled trials and observational studies will enrol adult or paediatric patients presenting with URTI treated by BMP approved by the Brazilian Health Surveillance Agency compared with placebo, no treatment or an alternative therapy. Our search will include the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Illness Group's Specialized Register; MEDLINE; EMBASE; CINAHL (Cumulative Index to Nursing and Allied Health Literature); Web of Science; AMED; LILACS; CAB abstracts; clinical trial.gov; the WHO Trial Register and the Brazilian thesis database (CAPES) without any language restrictions. Outcomes of interest are time to resolution of clinical symptoms and/or signs (cough, sputum production or activity limitations), severity of symptoms prior to resolution and major/minor adverse events. Teams of reviewers will, independently and in duplicate, screen titles and abstracts and the complete full text to determine eligibility. For eligible studies, reviewers will perform data abstraction and assess risk of bias of eligible trials. When appropriate, we will conduct meta-analyses. We will also assess the quality of body of evidence (confidence in estimates of effect) for each of the outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Ethics and dissemination The systematic review will be published in a peer-reviewed journal. Brief reports of review findings will be disseminated directly to appropriate audiences via email and other modes of communication. The review will guide healthcare practice and policy in Brazil. Trial registration number Prospero CRD42014007057. PMID:25056973

Interventions for the management of taste disturbances.

PubMed

Nagraj, Sumanth Kumbargere; Naresh, Shetty; Srinivas, Kandula; Renjith George, P; Shrestha, Ashish; Levenson, David; Ferraiolo, Debra M

2014-11-26

The sense of taste is very much essential to the overall health of the individual. It is a necessary component to enjoying one's food, which in turn provides nutrition to an individual. Any disturbance in taste perception can hamper the quality of life in such patients by influencing their appetite, body weight and psychological well-being. Taste disorders have been treated using different modalities of treatment and there is no consensus for the best intervention. Hence this Cochrane systematic review was undertaken. To assess the effects of interventions for the management of patients with taste disturbances. We searched the Cochrane Oral Health Group Trials Register (to 5 March 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2014), MEDLINE via OVID (1948 to 5 March 2014), EMBASE via OVID (1980 to 5 March 2014), CINAHL via EBSCO (1980 to 5 March 2014) and AMED via OVID (1985 to 5 March 2014). We also searched the relevant clinical trial registries and conference proceedings from the International Association of Dental Research/American Association of Dental Research (to 5 March 2014), Association for Research in Otolaryngology (to 5 March 2014), the US National Institutes of Health Trials Register (to 5 March 2014), metaRegister of Controlled Trials (mRCT) (to 5 March 2014), World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) (to 5 March 2014) and International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) Clinical Trials Portal (to 5 March 2014). We included all randomised controlled trials (RCTs) comparing any pharmacological agent with a control intervention or any non-pharmacological agent with a control intervention. We also included cross-over trials in the review. Two authors independently, and in duplicate, assessed the quality of trials and extracted data. Wherever possible, we contacted study authors for additional information. We collected adverse events information from the trials. We included nine trials (seven parallel and two cross-over RCTs) with 566 participants. We assessed three trials (33.3%) as having a low risk of bias, four trials (44.5%) at high risk of bias and two trials (22.2%) as having an unclear risk of bias. We only included studies on taste disorders in this review that were either idiopathic, or resulting from zinc deficiency or chronic renal failure.Of these, eight trials with 529 people compared zinc supplements to placebo for patients with taste disorders. The participants in two trials were children and adolescents with respective mean ages of 10 and 11.2 years and the other six trials had adult participants. Out of these eight, two trials assessed the patient reported outcome for improvement in taste acuity using zinc supplements (RR 1.45, 95% CI 1.0 to 2.1; very low quality evidence). We included three trials in the meta-analysis for overall taste improvement (effect size 0.44, 95% CI 0.23 to 0.65; moderate quality evidence). Two other trials described the results as taste acuity improvement and we conducted subgroup analyses due to clinical heterogeneity. One trial described the results as taste recognition improvement for each taste sensation and we analysed this separately. We also analysed one cross-over trial separately using the first half of the results. None of the zinc trials tested taste discrimination. Only one trial tested taste discrimination using acupuncture (effect size 2.80, 95% CI -1.18 to 6.78; low quality evidence).Out of the eight trials using zinc supplementation, four reported adverse events like eczema, nausea, abdominal pain, diarrhoea, constipation, decrease in blood iron, increase in blood alkaline phosphatase, and minor increase in blood triglycerides. No adverse events were reported in the acupuncture trial.None of the included trials could be included in the meta-analysis for health-related quality of life in taste disorder patients. We found very low quality evidence that was insufficient to conclude on the role of zinc supplements to improve taste perception by patients, however we found moderate quality evidence that zinc supplements improve overall taste improvement in patients with zinc deficiency/idiopathic taste disorders. We also found low quality evidence that zinc supplements improve taste acuity in zinc deficient/idiopathic taste disorders and very low quality evidence for taste recognition improvement in children with taste disorders secondary to chronic renal failure. We did not find any evidence to conclude the role of zinc supplements for improving taste discrimination, or any evidence addressing health-related quality of life due to taste disorders.We found low quality evidence that is not sufficient to conclude on the role of acupuncture for improving taste discrimination in cases of idiopathic dysgeusia (distortion of taste) and hypogeusia (reduced ability to taste). We were unable to draw any conclusions regarding the superiority of zinc supplements or acupuncture as none of the trials compared these interventions.

Therapeutic Plasma Transfusion in Bleeding Patients: A Systematic Review.

PubMed

Levy, Jerrold H; Grottke, Oliver; Fries, Dietmar; Kozek-Langenecker, Sibylle

2017-04-01

Plasma products, including fresh frozen plasma, are administered extensively in a variety of settings from massive transfusion to vitamin K antagonist reversal. Despite the widespread use of plasma as a hemostatic agent in bleeding patients, its effect in comparison with other available choices of hemostatic therapies is unclear. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed Central, and databases of ongoing trials for randomized controlled trials that assessed the efficacy and/or safety of therapeutic plasma as an intervention to treat bleeding patients compared with other interventions or placebo. Of 1243 unique publications retrieved in our initial search, no randomized controlled trials were identified. Four nonrandomized studies described the effect of therapeutic plasma in bleeding patients; however, data gathered from these studies did not allow for comparison with other therapeutic interventions primarily as a result of the low number of patients and the use of different (or lack of) comparators. We identified two ongoing trials investigating the efficacy and safety of therapeutic plasma, respectively; however, no data have been released as yet. Although plasma is used extensively in the treatment of bleeding patients, evidence from randomized controlled trials comparing its effect with those of other therapeutic interventions is currently lacking.

Methodological developments in searching for studies for systematic reviews: past, present and future?

PubMed

Lefebvre, Carol; Glanville, Julie; Wieland, L Susan; Coles, Bernadette; Weightman, Alison L

2013-09-25

The Cochrane Collaboration was established in 1993, following the opening of the UK Cochrane Centre in 1992, at a time when searching for studies for inclusion in systematic reviews was not well-developed. Review authors largely conducted their own searches or depended on medical librarians, who often possessed limited awareness and experience of systematic reviews. Guidance on the conduct and reporting of searches was limited. When work began to identify reports of randomized controlled trials (RCTs) for inclusion in Cochrane Reviews in 1992, there were only approximately 20,000 reports indexed as RCTs in MEDLINE and none indexed as RCTs in Embase. No search filters had been developed with the aim of identifying all RCTs in MEDLINE or other major databases. This presented The Cochrane Collaboration with a considerable challenge in identifying relevant studies.Over time, the number of studies indexed as RCTs in the major databases has grown considerably and the Cochrane Central Register of Controlled Trials (CENTRAL) has become the best single source of published controlled trials, with approximately 700,000 records, including records identified by the Collaboration from Embase and MEDLINE. Search filters for various study types, including systematic reviews and the Cochrane Highly Sensitive Search Strategies for RCTs, have been developed. There have been considerable advances in the evidence base for methodological aspects of information retrieval. The Cochrane Handbook for Systematic Reviews of Interventions now provides detailed guidance on the conduct and reporting of searches. Initiatives across The Cochrane Collaboration to improve the quality inter alia of information retrieval include: the recently introduced Methodological Expectations for Cochrane Intervention Reviews (MECIR) programme, which stipulates 'mandatory' and 'highly desirable' standards for various aspects of review conduct and reporting including searching, the development of Standard Training Materials for Cochrane Reviews and work on peer review of electronic search strategies. Almost all Cochrane Review Groups and some Cochrane Centres and Fields now have a Trials Search Co-ordinator responsible for study identification and medical librarians and other information specialists are increasingly experienced in searching for studies for systematic reviews.Prospective registration of clinical trials is increasing and searching trials registers is now mandatory for Cochrane Reviews, where relevant. Portals such as the WHO International Clinical Trials Registry Platform (ICTRP) are likely to become increasingly attractive, given concerns about the number of trials which may not be registered and/or published. The importance of access to information from regulatory and reimbursement agencies is likely to increase. Cross-database searching, gateways or portals and improved access to full-text databases will impact on how searches are conducted and reported, as will services such as Google Scholar, Scopus and Web of Science. Technologies such as textual analysis, semantic analysis, text mining and data linkage will have a major impact on the search process but efficient and effective updating of reviews may remain a challenge.In twenty years' time, we envisage that the impact of universal social networking, as well as national and international legislation, will mean that all trials involving humans will be registered at inception and detailed trial results will be routinely available to all. Challenges will remain, however, to ensure the discoverability of relevant information in diverse and often complex sources and the availability of metadata to provide the most efficient access to information. We envisage an ongoing role for information professionals as experts in identifying new resources, researching efficient ways to link or mine them for relevant data and managing their content for the efficient production of systematic reviews.

Methodological developments in searching for studies for systematic reviews: past, present and future?

PubMed Central

2013-01-01

The Cochrane Collaboration was established in 1993, following the opening of the UK Cochrane Centre in 1992, at a time when searching for studies for inclusion in systematic reviews was not well-developed. Review authors largely conducted their own searches or depended on medical librarians, who often possessed limited awareness and experience of systematic reviews. Guidance on the conduct and reporting of searches was limited. When work began to identify reports of randomized controlled trials (RCTs) for inclusion in Cochrane Reviews in 1992, there were only approximately 20,000 reports indexed as RCTs in MEDLINE and none indexed as RCTs in Embase. No search filters had been developed with the aim of identifying all RCTs in MEDLINE or other major databases. This presented The Cochrane Collaboration with a considerable challenge in identifying relevant studies. Over time, the number of studies indexed as RCTs in the major databases has grown considerably and the Cochrane Central Register of Controlled Trials (CENTRAL) has become the best single source of published controlled trials, with approximately 700,000 records, including records identified by the Collaboration from Embase and MEDLINE. Search filters for various study types, including systematic reviews and the Cochrane Highly Sensitive Search Strategies for RCTs, have been developed. There have been considerable advances in the evidence base for methodological aspects of information retrieval. The Cochrane Handbook for Systematic Reviews of Interventions now provides detailed guidance on the conduct and reporting of searches. Initiatives across The Cochrane Collaboration to improve the quality inter alia of information retrieval include: the recently introduced Methodological Expectations for Cochrane Intervention Reviews (MECIR) programme, which stipulates 'mandatory’ and 'highly desirable’ standards for various aspects of review conduct and reporting including searching, the development of Standard Training Materials for Cochrane Reviews and work on peer review of electronic search strategies. Almost all Cochrane Review Groups and some Cochrane Centres and Fields now have a Trials Search Co-ordinator responsible for study identification and medical librarians and other information specialists are increasingly experienced in searching for studies for systematic reviews. Prospective registration of clinical trials is increasing and searching trials registers is now mandatory for Cochrane Reviews, where relevant. Portals such as the WHO International Clinical Trials Registry Platform (ICTRP) are likely to become increasingly attractive, given concerns about the number of trials which may not be registered and/or published. The importance of access to information from regulatory and reimbursement agencies is likely to increase. Cross-database searching, gateways or portals and improved access to full-text databases will impact on how searches are conducted and reported, as will services such as Google Scholar, Scopus and Web of Science. Technologies such as textual analysis, semantic analysis, text mining and data linkage will have a major impact on the search process but efficient and effective updating of reviews may remain a challenge. In twenty years’ time, we envisage that the impact of universal social networking, as well as national and international legislation, will mean that all trials involving humans will be registered at inception and detailed trial results will be routinely available to all. Challenges will remain, however, to ensure the discoverability of relevant information in diverse and often complex sources and the availability of metadata to provide the most efficient access to information. We envisage an ongoing role for information professionals as experts in identifying new resources, researching efficient ways to link or mine them for relevant data and managing their content for the efficient production of systematic reviews. PMID:24066664

Prophylactic antibiotics for manual removal of retained placenta in vaginal birth.

PubMed

Chongsomchai, Chompilas; Lumbiganon, Pisake; Laopaiboon, Malinee

2014-10-20

Retained placenta is a potentially life-threatening condition because of its association with postpartum hemorrhage. Manual removal of placenta increases the likelihood of bacterial contamination in the uterine cavity. To compare the effectiveness and side-effects of routine antibiotic use for manual removal of placenta in vaginal birth in women who received antibiotic prophylaxis and those who did not and to identify the appropriate regimen of antibiotic prophylaxis for this procedure. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2014). All randomized controlled trials comparing antibiotic prophylaxis and placebo or non antibiotic use to prevent endometritis after manual removal of placenta in vaginal birth. There are no included trials. In future updates, if we identify eligible trials, two review authors will independently assess trial quality and extract data No studies that met the inclusion criteria were identified. There are no randomized controlled trials to evaluate the effectiveness of antibiotic prophylaxis to prevent endometritis after manual removal of placenta in vaginal birth.

Costs and Effects of Abdominal versus Laparoscopic Hysterectomy: Systematic Review of Controlled Trials

PubMed Central

Bijen, Claudia B. M.; Vermeulen, Karin M.; Mourits, Marian J. E.; de Bock, Geertruida H.

2009-01-01

Objective Comparative evaluation of costs and effects of laparoscopic hysterectomy (LH) and abdominal hysterectomy (AH). Data sources Controlled trials from Cochrane Central register of controlled trials, Medline, Embase and prospective trial registers. Selection of studies Twelve (randomized) controlled studies including the search terms costs, laparoscopy, laparotomy and hysterectomy were identified. Methods The type of cost analysis, perspective of cost analyses and separate cost components were assessed. The direct and indirect costs were extracted from the original studies. For the cost estimation, hospital stay and procedure costs were selected as most important cost drivers. As main outcome the major complication rate was taken. Findings Analysis was performed on 2226 patients, of which 1013 (45.5%) in the LH group and 1213 (54.5%) in the AH group. Five studies scored ≥10 points (out of 19) for methodological quality. The reported total direct costs in the LH group ($63,997) were 6.1% higher than the AH group ($60,114). The reported total indirect costs of the LH group ($1,609) were half of the total indirect in the AH group ($3,139). The estimated mean major complication rate in the LH group (14.3%) was lower than in the AH group (15.9%). The estimated total costs in the LH group were $3,884 versus $3,312 in the AH group. The incremental costs for reducing one patient with major complication(s) in the LH group compared to the AH group was $35,750. Conclusions The shorter hospital stay in the LH group compensates for the increased procedure costs, with less morbidity. LH points in the direction of cost effectiveness, however further research is warranted with a broader costs perspective including long term effects as societal benefit, quality of life and survival. PMID:19806210

Effect of acupuncture and its influence on cerebral activity in perimenopausal insomniacs: study protocol for a randomized controlled trial.

PubMed

Wu, Xiao; Zhang, Wei; Qin, Yuanyuan; Liu, Xuguang; Wang, Zhengyan

2017-08-14

Perimenopausal insomnia is one of the core symptoms of the menopausal transition. Acupuncture is considered to exert a positive effect on restoring the normal sleep-wake cycle. However, there is little intuitive evidence besides evaluation using clinical effectiveness scales. We therefore designed this study, aiming to use more intuitive and reliable detection techniques such as functional magnetic resonance imaging before and after applying acupuncture to provide neuroimaging evidence, as well as to verify the effectiveness with other curative effect indicators. This study is a randomized, assessor-statistician-blinded, positive medicine controlled trial involving 40 participants. A total of 40 eligible patients with perimenopausal insomnia will be randomly assigned to two groups in a 1:1 ratio as an intervention group using acupuncture and a control group taking estazolam. Participants in the intervention group will receive six acupuncture treatment sessions per week for 4 consecutive weeks, for a total of 24 sessions during the study. Meanwhile, the medicine control group will be prescribed estazolam 1-2 mg/day to be taken 30 minutes before sleep for 4 weeks. The primary outcome is the Pittsburgh Sleep Quality Index. Secondary outcomes are the micro-movement sensitive mattress-type sleep monitoring system, the Hamilton Depression Scale, and the Hamilton Anxiety Scale. All outcomes will be evaluated before and after treatment. The safety of interventions will be assessed at every visit. The results of this trial, which will be available in 2018, will investigate the impact of acupuncture treating perimenopausal insomnia from assessment of the sleep architecture, hormone level, and emotional-circuit neurological function, and will uncover the effective mechanism of acupuncture regulating the emotional center integrated effect. Chinese Clinical Trials Register, ChCTR-IPC-16007832 . Registered on 26 January 2016.

Effectiveness and cost effectiveness of counselling in primary care.

PubMed

Bower, P; Rowland, N

2006-07-19

The prevalence of mental health and psychosocial problems in primary care is high. This review examines the clinical and cost-effectiveness of psychological therapies provided in primary care by counsellors. To assess the effectiveness and cost effectiveness of counselling in primary care by reviewing cost and outcome data in randomised controlled trials for patients with psychological and psychosocial problems considered suitable for counselling. To update the review, the following electronic databases were searched on 25-10-2005: MEDLINE, EMBASE, PsycLIT, CINAHL, the Cochrane Controlled Trials register and the Cochrane Collaboration Depression, Anxiety and Neurosis (CCDAN) trials registers. All controlled trials comparing counselling in primary care with other treatments for patients with psychological and psychosocial problems considered suitable for counselling. Trials completed before the end of June 2005 were included in the review. Data were extracted using a standardised data extraction sheet. Trials were rated for quality using CCDAN criteria, to assess the extent to which their design and conduct were likely to have prevented systematic error. Continuous measures of outcome were combined using standardised mean differences. An overall effect size was calculated for each outcome with 95% confidence intervals (CI). Continuous data from different measuring instruments were transformed into a standard effect size by dividing mean values by standard deviations. Sensitivity analyses were undertaken to test the robustness of the results. Economic analyses were summarised in narrative form. Eight trials were included in the review. The analysis found significantly greater clinical effectiveness in the counselling group compared with usual care in the short-term (standardised mean difference -0.28, 95% CI -0.43 to -0.13, n = 772, 6 trials) but not the long-term (standardised mean difference -0.09, 95% CI -0.27 to 0.10, n = 475, 4 trials). Levels of satisfaction with counselling were high. There was some evidence that the overall costs of counselling and usual care were similar. Counselling is associated with modest improvement in short-term outcome compared to usual care, but provides no additional advantages in the long-term. Patients are satisfied with counselling. Although some types of health care utilisation may be reduced, counselling does not seem to reduce overall healthcare costs.

Interventions in the workplace to support breastfeeding for women in employment.

PubMed

Abdulwadud, O A; Snow, M E

2007-07-18

In recent years there has been a rise in the participation rate of women in employment. Some may become pregnant while in employment and subsequently deliver their babies. Most may decide to return early to work after giving birth for various reasons. Unless these mothers get support from their employers and fellow employees, they might give up breastfeeding when they return to work. As a result, the duration and exclusivity of breastfeeding to the recommended age of the babies would be affected. Workplace environment can play a positive role to promote breastfeeding. For women going back to work, various types of workplace support interventions are available and this should not be ignored by employers. Notably, promoting breastfeeding in a workplace may have benefits for the women, the baby and also the employer. To assess the effectiveness of workplace interventions to support and promote breastfeeding among women returning to paid work after the birth of their children, and its impact on process outcomes pertinent to employees and employers. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (November 2006), CINAHL (1982 to November week 1 2006), LILACS (2 August 2006), Social Services Abstracts (1979 to November 2006), Sociological Abstracts (1952 to November 2006), Australian Public Affairs Information Service (2003 to 2006), Australian Family and Society Abstracts (2003 to 2006), International Bibliography of the Social Sciences (1951 to 2006), ProQuest Social Science Journals (1994 to 2006), Middle Eastern and Central Asian Studies (1900 to 2006) and the Campbell Collaboration Register (C2-SPECTR) (November 2006). Two authors independently assessed all identified studies for randomised controlled trials and quasi-randomised controlled trials that compared workplace interventions with no intervention or two or more workplace interventions against each other. Two authors planned to evaluate the methodological quality of the eligible trials and extract data. There were no randomised controlled trials or quasi-randomised controlled trials identified. No trials have evaluated the effectiveness of workplace interventions in promoting breastfeeding among women returning to paid work after the birth of their child. The impact of such intervention on process outcomes is also unknown. Randomised controlled trials are required to establish the benefits of various types of workplace interventions to support, encourage and promote breastfeeding among working mothers.

Aspirin for in vitro fertilisation.

PubMed

Siristatidis, Charalambos S; Dodd, Susanna R; Drakeley, Andrew J

2011-08-10

Aspirin is used to improve the outcome in women undergoing in vitro fertilisation despite inconsistent evidence of its efficacy. The most appropriate time to commence aspirin therapy and the length of treatment required are also still to be determined. This is an update of the review first published in 2007. To determine the effectiveness and safety of aspirin for improving the outcome of in vitro fertilisation and intracytoplasmic sperm injection treatment cycles. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library January 2011), MEDLINE (1966 to January 2011) and EMBASE (1980 to January 2011) databases. We used the research terms: "(aspirin OR acetylsalicylic acid) AND (in-vitro fertilisation OR intracytoplasmic sperm injection)", combined with the Cochrane Menstrual Disorders and Subfertility Group's search strategy, in order to identify randomised controlled trials on aspirin for women undergoing in vitro fertilisation. Randomised controlled trials. Two authors independently selected studies to include in the review, extracted data and assessed trial quality. The searches identified 13 trials which were eligible for inclusion in the review, including a total of 2653 participants. No significant differences were found between the treatment and control groups for any of the outcomes assessed. No significant differences were found in the meta-analysis of studies investigating the effect of aspirin compared with control on live birth rate (RR 0.91, 95% CI 0.72 to 1.15; three studies and 1053 participants), clinical pregnancy rate (RR 1.03, 95% CI 0.91 to 1.17; 10 studies and 2142 participants), ectopic and miscarriage rates (RR 1.86, 95% CI 0.75 to 4.63; RR 1.10, 95% CI 0.68 to 1.77) respectively (three and five studies involving 1135 and 1497 participants). Use of aspirin for women undergoing in vitro fertilisation cannot be recommended due to lack of evidence from the current trial data. Adequately powered trials are needed. It was proposed in the initial version of this review that a sample size of 350 women in each group would be required in order to demonstrate a 10% improvement from the use of aspirin, with 80% power at the 5% significance level. Until such evidence is available, this treatment can not be recommended.

Educational and Skills-Based Interventions to Prevent Relationship Violence in Young People

ERIC Educational Resources Information Center

Fellmeth, Gracia; Heffernan, Catherine; Nurse, Joanna; Habibula, Shakiba; Sethi, Dinesh

2015-01-01

Objectives: To assess the efficacy of educational and skills-based interventions to prevent relationship and dating violence in adolescents and young adults. Methods: We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, and other databases for randomized, cluster-randomized, and quasi-randomized…

A randomised controlled trial of six weeks of home enteral nutrition versus standard care after oesophagectomy or total gastrectomy for cancer: report on a pilot and feasibility study.

PubMed

Bowrey, David J; Baker, Melanie; Halliday, Vanessa; Thomas, Anne L; Pulikottil-Jacob, Ruth; Smith, Karen; Morris, Tom; Ring, Arne

2015-11-21

Poor nutrition in the first months after oesophago-gastric resection is a contributing factor to the reduced quality of life seen in these patients. The aim of this pilot and feasibility study was to ascertain the feasibility of conducting a multi-centre randomised controlled trial to evaluate routine home enteral nutrition in these patients. Patients undergoing oesophagectomy or total gastrectomy were randomised to either six weeks of home feeding through a jejunostomy (intervention), or treatment as usual (control). Intervention comprised overnight feeding, providing 50 % of energy and protein requirements, in addition to usual oral intake. Primary outcome measures were recruitment and retention rates at six weeks and six months. Nutritional intake, nutritional parameters, quality of life and healthcare costs were also collected. Interviews were conducted with a sample of participants, to ascertain patient and carer experiences. Fifty-four of 112 (48 %) eligible patients participated in the study over the 20 months. Study retention at six weeks was 41/54 patients (76 %) and at six months was 36/54 (67 %). At six weeks, participants in the control group had lost on average 3.9 kg more than participants in the intervention group (95 % confidence interval [CI] 1.6 to 6.2). These differences remained evident at three months (mean difference 2.5 kg, 95 % CI -0.5 to 5.6) and at six months (mean difference 2.5 kg, 95 % CI -1.2 to 6.1). The mean values observed in the intervention group for mid arm circumference, mid arm muscle circumference, triceps skin fold thickness and right hand grip strength were greater than for the control group at all post hospital discharge time points. The economic evaluation suggested that it was feasible to collect resource use and EQ-5D data for a full cost-effectiveness analysis. Thematic analysis of 15 interviews identified three main themes related to the intervention and the trial: 1) a positive experience, 2) the reasons for taking part, and 3) uncertainty of the study process. This study demonstrated that home enteral feeding by jejunostomy was feasible, safe and acceptable to patients and their carers. Whether home enteral feeding as 'usual practice' is a cost-effective therapy would require confirmation in an appropriately powered, multi-centre study. UK Clinical Research Network ID 12447 (main trial, first registered 30 May 2012); UK Clinical Research Network ID 13361 (qualitative substudy, first registered 30 May 2012); ClinicalTrials.gov NCT01870817 (first registered 28 May 2013).

Subterranean termite control examinations on current and former experimental forests and ranges

Treesearch

T. G. Shelton; T. L. Wagner; C. J Peterson; J. E. Mulrooney

2014-01-01

For more than 70 years, the USDA Forest Service’s Termite Team has engaged in research to extend the life of wood in service by studying chemical (and a few nonchemical) subterranean termite control products. These efficacy data are produced in distinct field trials on experimental forests across the USA, and are used by industry cooperators to register their products...

Trial Registration at ClinicalTrials.gov between May and October 2005

PubMed Central

Zarin, Deborah A.; Tse, Tony; Ide, Nicholas C.

2006-01-01

BACKGROUND Clinical trial registration allows interested parties to obtain information about ongoing and completed trials, but there are few data indicating the quality of the information provided during the registration process. We used information in the publicly available ClinicalTrials.gov database to describe patterns of trial registration before and after the implementation by journal editors of a new policy requiring registration as a prerequisite for publication. METHODS We reviewed ClinicalTrials.gov records to determine patterns of completion of the “Intervention Name” and “Primary Outcome Measure” data fields for trials registered on May 20 and October 11, 2005, and for trials registered during the interval between these two dates, inclusively. RESULTS During the interval studied, the number of registrations in ClinicalTrials.gov increased by 73 percent from 13,153 to 22,714. The percentage of interventional trials registered by industry with nonspecific Intervention Name entries (attributable to four drug companies) decreased from 10 percent to 2 percent; all other industry and nonindustry records contained specific entries in this field. Of the 2670 studies registered by industry between the two dates, 76 percent provided information in the Primary Outcome Measure field, although these entries varied markedly in their degree of specificity. In the remaining 24 percent of the records, this field was blank. CONCLUSIONS During the summer of 2005, there were large increases in the number of clinical trial registrations. Overall, the data contained in records were more complete in October than they were in May, but there still is room for substantial improvement. PMID:16382064

Massage therapy for preventing pressure ulcers.

PubMed

Zhang, Qinhong; Sun, Zhongren; Yue, Jinhuan

2015-06-17

Pressure ulcers affect approximately 10% of patients in hospitals and the elderly are at highest risk. Several studies have suggested that massage therapy may help to prevent the development of pressure ulcers, but these results are inconsistent. To assess the evidence for the effects of massage compared with placebo, standard care or other interventions for prevention of pressure ulcers in at-risk populations.The review sought to answer the following questions:Does massage reduce the incidence of pressure ulcers of any grade?Is massage safe in the short- and long-term? If not, what are the adverse events associated with massage? We searched the Cochrane Wounds Group Specialised Register (8 January 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 1), Ovid MEDLINE (1946 to 8 January 2015), Ovid MEDLINE (In-Process Other Non-Indexed Citations 8 January 2015), Ovid EMBASE (1974 to 8 January 2015), and EBSCO CINAHL (1982 to 8 January 2015). We did not apply date or language restrictions. We planned to include all randomised controlled trials (RCTs) and quasi-randomised controlled trials (Q-RCTs) that evaluated the effects of massage therapy for the prevention of pressure ulcers. Our primary outcome was the proportion of people developing a new pressure ulcer of any grade. Two review authors independently carried out trial selection. Disagreements were resolved by discussion. No studies (RCTs or Q-RCTs) met the inclusion criteria. Therefore, neither a meta-analysis nor a narrative description of studies was possible. There are currently no studies eligible for inclusion in this review. It is, therefore, unclear whether massage therapy can prevent pressure ulcers.

Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial.

PubMed

Santarius, Thomas; Kirkpatrick, Peter J; Ganesan, Dharmendra; Chia, Hui Ling; Jalloh, Ibrahim; Smielewski, Peter; Richards, Hugh K; Marcus, Hani; Parker, Richard A; Price, Stephen J; Kirollos, Ramez W; Pickard, John D; Hutchinson, Peter J

2009-09-26

Chronic subdural haematoma causes serious morbidity and mortality. It recurs after surgical evacuation in 5-30% of patients. Drains might reduce recurrence but are not used routinely. Our aim was to investigate the effect of drains on recurrence rates and clinical outcomes. We did a randomised controlled trial at one UK centre between November, 2004, and November, 2007. 269 patients aged 18 years and older with a chronic subdural haematoma for burr-hole drainage were assessed for eligibility. 108 were randomly assigned by block randomisation to receive a drain inserted into the subdural space and 107 to no drain after evacuation. The primary endpoint was recurrence needing redrainage. The trial was stopped early because of a significant benefit in reduction of recurrence. Analyses were done on an intention-to-treat basis. This study is registered with the International Standard Randomised Controlled Trial Register (ISRCTN 97314294). Recurrence occurred in ten of 108 (9.3%) people with a drain, and 26 of 107 (24%) without (p=0.003; 95% CI 0.14-0.70). At 6 months mortality was nine of 105 (8.6%) and 19 of 105 (18.1%), respectively (p=0.042; 95% CI 0.1-0.99). Medical and surgical complications were much the same between the study groups. Use of a drain after burr-hole drainage of chronic subdural haematoma is safe and associated with reduced recurrence and mortality at 6 months. Academy of Medical Sciences, Health Foundation, and NIHR Biomedical Research Centre (Neurosciences Theme).

Effect of acupuncture on patients with insomnia: study protocol for a randomized controlled trial.

PubMed

Han, Kyung-Hun; Kim, Sang-Young; Chung, Sun-Yong

2014-10-23

Hypnotic drugs tend to be the dominant form of treatment of insomnia, but these come with a number of reported side effects. Acupuncture has been studied as an alternative, resulting in a rising need for methodological research towards verifying its efficacy as insomnia treatment. We describe a proposal for a single-center, patient-assessor-blinded, randomized controlled trial with two parallel arms. A total of 38 patients complete screening tests at the first visit, are registered into the clinical trial, and then randomly assigned to the experimental or sham control groups (19 patients for each group). All subjects are clinical insomnia patients who score a 6 or above on the Pittsburgh Sleep Quality Index (PSQI) and meet all inclusion criteria. All subjects are treated with acupuncture and intradermal acupuncture (IDA) three times during the first week. Five sham acupoints are used in the control group. In the experimental group, five real acupoints (PC6, SP6, HT7, KI6, and BL62) are used unilaterally in turn. Sham acupoints are over 1 cm away from each real acupoint.The primary outcomes are the scores on the Insomnia Severity Index (ISI) and PSQI. Secondary outcomes are the sleep log, the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), the World Health Organization Quality of Life Abbreviated Version (WHOQOL-BREF), the Korean-Auditory Verbal Learning Test (K-AVLT), the Digit Span Test (DS), Event Related Potentials (ERPs) and heart rate variability (HRV) to assess emotional states, sleep quality, cognitive functioning, and electro-physiological changes.Subjects are assessed at three time points: baseline, post-treatment and follow-up. The duration of the clinical trial is 18 days. To study the enhancement of the effectiveness of acupuncture for insomnia, we test the intradermal acupuncture method, which is performed continuously on the subject's skin and stimulated at home by the subject every night. In the trial, objective measurements including ERPs and HRV are used to evaluate states of cognition and autonomic nervous system functioning and subjective self-report questionnaires assess insomnia symptoms.'Sham' acupuncture points provided by STRICTA are used for the control group. ClinicalTrials.gov: NCT01956760, registered 5 September 2013.

Can Healthcare Assistant Training (CHAT) improve the relational care of older people? Study protocol for a pilot cluster randomised controlled trial.

PubMed

Arthur, Antony; Maben, Jill; Wharrad, Heather; Aldus, Clare; Sarre, Sophie; Schneider, Justine; Nicholson, Caroline; Barton, Garry; Cox, Karen; Clark, Allan

2015-12-09

People aged 75 years and over account for 1 in 4 of all hospital admissions. There has been increasing recognition of problems in the care of older people, particularly in hospitals. Evidence suggests that older people judge the care they receive in terms of kindness, empathy, compassion, respectful communication and being seen as a person not just a patient. These are aspects of care to which we refer when we use the term 'relational care'. Healthcare assistants deliver an increasing proportion of direct care to older people, yet their training needs are often overlooked. This study will determine the acceptability and feasibility of a cluster randomised controlled trial of 'Older People's Shoes' a 2-day training intervention for healthcare assistants caring for older people in hospital. Within this pilot, 2-arm, parallel, cluster randomised controlled trial, healthcare assistants within acute hospital wards are randomised to either the 2-day training intervention or training as usual. Registered nurses deliver 'Older People's Shoes' over 2 days, approximately 1 week apart. It contains three components: experiential learning about ageing, exploration of older people's stories, and customer care. Outcomes will be measured at the level of patient (experience of emotional care and quality of life during their hospital stay), healthcare assistant (empathy and attitudes towards older people), and ward (quality of staff/patient interaction). Semi-structured interviews of a purposive sample of healthcare assistants receiving the intervention, and all trainers delivering the intervention, will be undertaken to gain insights into the experiences of both the intervention and the trial, and its perceived impact on practice. Few training interventions for care staff have been rigorously tested using randomised designs. This study will establish the viability of a definitive cluster randomised controlled trial of a new training intervention to improve the relational care proided by healthcare assistants working with older people in hospital. The study was registered as an International Standard Randomised Controlled Trial ( ISRCTN10385799 ) on 29 December 2014.

A novel dynamic exercise initiative for older people to improve health and well-being: study protocol for a randomised controlled trial.

PubMed

Sales, Myrla Patricia Reis; Polman, Remco; Hill, Keith D; Karaharju-Huisman, Tuire; Levinger, Pazit

2015-06-24

Exercise is an important and effective approach to preventing falls in older people, but adherence to exercise participation remains a persistent problem. A unique purpose-built exercise park was designed to provide a fun but physically challenging environment to support exercise in a community setting. This project is a randomised controlled trial designed to evaluate the effectiveness of an exercise intervention using an exercise park specifically designed for older people in reducing the risk of falls. This study will be a parallel randomised control trial with pre and post intervention design. One hundred and twenty people aged between 60 and 90 years old will be recruited from Melbourne suburbs and will be randomly allocated to either an exercise park intervention group (EPIG) or a control group (CG). The CG will receive social activities and an educational booklet on falls prevention. The BOOMER balance test will be used as the primary outcome measure. Secondary outcome measures will include hand grip strength, two minute walk test, lower limb strength test, spatio-temporal walking parameters, health related quality of life, feasibility, adherence, safety, and a number of other psychosocial measures. Outcome assessment will be conducted at baseline and at 18 and 26 weeks after intervention commencement. Participants will inform their falls and physical activity history for a 12-month period via monthly calendars. Mixed linear modelling incorporating intervention and control groups at the baseline and two follow up time points (18 weeks and 26 weeks after intervention commencement) will be used to assess outcomes. This planned trial will be the first to provide evidence if the exercise park can improve functional and physiological health, psychological and well-being. In addition, this study will provide empirical evidence for effectiveness and explore the barriers to participation and the acceptability of the senior exercise park in the Australian older community. This trial is registered with the Australian New Zealand Clinical Trials Registry-Registry No. ACTRN12614000700639 registered on Jul 3rd 2014.

The efficacy of a behavioral activation intervention among depressed US Latinos with limited English language proficiency: study protocol for a randomized controlled trial.

PubMed

Collado, Anahi; Long, Katherine E; MacPherson, Laura; Lejuez, Carl W

2014-06-18

Major depressive disorder is highly prevalent among Latinos with limited English language proficiency in the United States. Although major depressive disorder is highly treatable, barriers to depression treatment have historically prevented Latinos with limited English language proficiency from accessing effective interventions. The project seeks to evaluate the efficacy of behavioral activation treatment for depression, an empirically supported treatment for depression, as an intervention that may address some of the disparities surrounding the receipt of efficacious mental health care for this population. Following a pilot study of behavioral activation treatment for depression with 10 participants which yielded very promising results, the current study is a randomized control trial testing behavioral activation treatment for depression versus a supportive counseling treatment for depression. We are in the process of recruiting 60 Latinos with limited English language proficiency meeting criteria for major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders 4th and 5th Edition for participation in a single-center efficacy trial. Participants are randomized to receive 10 sessions of behavioral activation treatment for depression (n = 30) or 10 sessions of supportive counseling (n = 30). Assessments occur prior to each session and at 1 month after completing treatment. Intervention targets include depressive symptomatology and the proposed mechanisms of behavioral activation treatment for depression: activity level and environmental reward. We will also examine other factors related to treatment outcome such as treatment adherence, treatment satisfaction, and therapeutic alliance. This randomized controlled trial will allow us to determine the efficacy of behavioral activation treatment for depression in a fast-growing, yet highly underserved population in US mental health services. The study is also among the first to examine the effect of the proposed mechanisms of change of behavioral activation treatment for depression (that is, activity level and environmental reward) on depression over time. To our knowledge, this is the first randomized controlled trial to compare an empirical-supported treatment to a control supportive counseling condition in a sample of depressed, Spanish-speaking Latinos in the United States. Clinical Trials Register: NCT01958840; registered 8 October 2013.

Comprehension of confidence intervals - development and piloting of patient information materials for people with multiple sclerosis: qualitative study and pilot randomised controlled trial.

PubMed

Rahn, Anne C; Backhus, Imke; Fuest, Franz; Riemann-Lorenz, Karin; Köpke, Sascha; van de Roemer, Adrianus; Mühlhauser, Ingrid; Heesen, Christoph

2016-09-20

Presentation of confidence intervals alongside information about treatment effects can support informed treatment choices in people with multiple sclerosis. We aimed to develop and pilot-test different written patient information materials explaining confidence intervals in people with relapsing-remitting multiple sclerosis. Further, a questionnaire on comprehension of confidence intervals was developed and piloted. We developed different patient information versions aiming to explain confidence intervals. We used an illustrative example to test three different approaches: (1) short version, (2) "average weight" version and (3) "worm prophylaxis" version. Interviews were conducted using think-aloud and teach-back approaches to test feasibility and analysed using qualitative content analysis. To assess comprehension of confidence intervals, a six-item multiple choice questionnaire was developed and tested in a pilot randomised controlled trial using the online survey software UNIPARK. Here, the average weight version (intervention group) was tested against a standard patient information version on confidence intervals (control group). People with multiple sclerosis were invited to take part using existing mailing-lists of people with multiple sclerosis in Germany and were randomised using the UNIPARK algorithm. Participants were blinded towards group allocation. Primary endpoint was comprehension of confidence intervals, assessed with the six-item multiple choice questionnaire with six points representing perfect knowledge. Feasibility of the patient information versions was tested with 16 people with multiple sclerosis. For the pilot randomised controlled trial, 64 people with multiple sclerosis were randomised (intervention group: n = 36; control group: n = 28). More questions were answered correctly in the intervention group compared to the control group (mean 4.8 vs 3.8, mean difference 1.1 (95 % CI 0.42-1.69), p = 0.002). The questionnaire's internal consistency was moderate (Cronbach's alpha = 0.56). The pilot-phase shows promising results concerning acceptability and feasibility. Pilot randomised controlled trial results indicate that the patient information is well understood and that knowledge gain on confidence intervals can be assessed with a set of six questions. German Clinical Trials Register: DRKS00008561 . Registered 8th of June 2015.

Cognitive rehabilitation for attention deficits following stroke.

PubMed

Loetscher, Tobias; Lincoln, Nadina B

2013-05-31

Many survivors of stroke complain about attentional impairments, such as diminished concentration and mental slowness. However, the effectiveness of cognitive rehabilitation for improving these impairments is uncertain. To determine whether (1) people receiving attentional treatment show better outcomes in their attentional functions than those given no treatment or treatment as usual, and (2) people receiving attentional treatment techniques have a better functional recovery, in terms of independence in activities of daily living, mood and quality of life, than those given no treatment or treatment as usual. We searched the Cochrane Stroke Group Trials Register (October 2012), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library October 2012), MEDLINE (1948 to October 2012), EMBASE (1947 to October 2012), CINAHL (1981 to October 2012), PsycINFO (1806 to October 2012), PsycBITE and REHABDATA (searched October 2012) and ongoing trials registers. We screened reference lists and tracked citations using Scopus. We included randomised controlled trials (RCTs) of cognitive rehabilitation for impairments of attention for people with stroke. The primary outcome was measures of global attentional functions, and secondary outcomes were measures of attention domains, functional abilities, mood and quality of life. Two review authors independently selected trials, extracted data and assessed trial quality. We included six RCTs with 223 participants. All six RCTs compared cognitive rehabilitation with a usual care control. Meta-analyses demonstrated no statistically significant effect of cognitive rehabilitation for persisting effects on global measures of attention (two studies, 99 participants; standardised mean difference (SMD) 0.16, 95% confidence interval (CI) -0.23 to 0.56; P value = 0.41), standardised attention assessments (two studies, 99 participants; P value ≥ 0.08) or functional outcomes (two studies, 99 participants; P value ≥ 0.15). In contrast, a statistically significant effect was found in favour of cognitive rehabilitation when compared with control for immediate effects on measures of divided attention (four studies, 165 participants; SMD 0.67, 95% CI 0.35 to 0.98; P value < 0.0001) but no significant effects on global attention (two studies, 53 participants; P value = 0.06), other attentional domains (six studies, 223 participants; P value ≥ 0.16) or functional outcomes (three studies, 109 participants; P value ≥ 0.21).Thus there was limited evidence that cognitive rehabilitation may improve some aspects of attention in the short term, but there was insufficient evidence to support or refute the persisting effects of cognitive rehabilitation on attention, or on functional outcomes in either the short or long term. The effectiveness of cognitive rehabilitation remains unconfirmed. The results suggest there may be a short-term effect on attentional abilities, but future studies need to assess the persisting effects and measure attentional skills in daily life. Trials also need to have higher methodological quality and better reporting.

Day care versus in-patient surgery for age-related cataract.

PubMed

Fedorowicz, Zbys; Lawrence, David; Gutierrez, Peter; van Zuuren, Esther J

2011-07-06

Age-related cataract accounts for more than 40% of cases of blindness in the world with the majority of people who are blind from cataract found in the developing world. With the increased number of people with cataract there is an urgent need for cataract surgery to be made available as a day care procedure. To provide reliable evidence for the safety, feasibility, effectiveness and cost-effectiveness of cataract extraction performed as day care versus in-patient procedure. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 5), MEDLINE (January 1950 to May 2011), EMBASE (January 1980 to May 2011), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to May 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 23 May 2011. We included randomised controlled trials comparing day care and in-patient surgery for age-related cataract. The primary outcome was the achievement of a satisfactory visual acuity six weeks after the operation. Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. Adverse effects information was collected from the trials. We included two trials (conducted in Spain and USA), involving 1284 people. One trial reported statistically significant differences in early postoperative complication rates in the day care group, with an increased risk of increased intraocular pressure, which had no clinical relevance to visual outcomes four months postoperatively. The mean change in visual acuity (Snellen lines) of the operated eye four months postoperatively was 4.1 (standard deviation (SD) 2.3) for the day care group and 4.1 (SD 2.2) for the in-patient group and not statistically significant. The four-month postoperative mean change in quality of life score measured using the VF14 showed minimal differences between the two groups. Costs were 20% more for the in-patient group and this was attributed to higher costs for overnight stay. One study only reported hotel costs for the non-hospitalised participants making aggregation of data on costs impossible. This review provides some evidence that there is a cost saving but no significant difference in outcome or risk of postoperative complications between day care and in-patient cataract surgery. This is based on one detailed and methodologically sound trial conducted in the developed world. The success, safety and cost-effectiveness of cataract surgery as a day care procedure appear to be acceptable. Future research may well focus on evidence provided by high quality clinical databases and registers which would enable clinicians and healthcare planners to agree clinical and social indications for in-patient care and so make better use of resources, by selecting day case surgery unless these criteria are met.

Implementation of a salaried compensation program for registered nurses.

PubMed

Sills, L R

1993-01-01

Compensation is a key variable in recruitment and retention of registered nurses. A 6-month trial of an exempt/salaried wage program for registered nurses, based on normative change theory, was implemented in the adult critical care division of a 491-bed community hospital. A total of 58 registered nurses participated in the trial. At the end of 6 months on salary, 94% (53) of the nurses voted to remain salaried. The staff perceived that the new wage program increased flexibility in work schedules and promoted teamwork and professional autonomy.

Analgesic effects of treatments for non-specific low back pain: a meta-analysis of placebo-controlled randomized trials.

PubMed

Machado, L A C; Kamper, S J; Herbert, R D; Maher, C G; McAuley, J H

2009-05-01

Estimates of treatment effects reported in placebo-controlled randomized trials are less subject to bias than those estimates provided by other study designs. The objective of this meta-analysis was to estimate the analgesic effects of treatments for non-specific low back pain reported in placebo-controlled randomized trials. Medline, Embase, Cinahl, PsychInfo and Cochrane Central Register of Controlled Trials databases were searched for eligible trials from earliest records to November 2006. Continuous pain outcomes were converted to a common 0-100 scale and pooled using a random effects model. A total of 76 trials reporting on 34 treatments were included. Fifty percent of the investigated treatments had statistically significant effects, but for most the effects were small or moderate: 47% had point estimates of effects of <10 points on the 100-point scale, 38% had point estimates from 10 to 20 points and 15% had point estimates of >20 points. Treatments reported to have large effects (>20 points) had been investigated only in a single trial. This meta-analysis revealed that the analgesic effects of many treatments for non-specific low back pain are small and that they do not differ in populations with acute or chronic symptoms.

Interventions for treating painful sickle cell crisis during pregnancy.

PubMed

Martí-Carvajal, Arturo J; Peña-Martí, Guiomar E; Comunián-Carrasco, Gabriella; Martí-Peña, Arturo J

2009-01-21

Sickle cell disease is a group of genetic haemoglobin disorders. All over the world, about 300,000 children with these disorders are born each year. Acute sickle cell pain episodes are the most common cause of hospitalisation. Pregnancy in women with sickle cell disease is associated with an increased incidence of maternal and fetal morbidity and mortality. The painful crisis is a severe complication of this illness, and it requires several interventions: packed red cell transfusion, fluid replacement therapy, analgesic drugs, oxygen therapy and steroids; but the approach is not standardised. To assess the effectiveness and safety of different regimens of packed red cell transfusion, oxygen therapy, fluid replacement therapy, analgesic drugs, and steroids for the treatment of painful sickle cell crisis during pregnancy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (December 2007), the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register (October 2007), LILACS database (1982 to December 2007) and the following web sites: ClinicalTrials.gov (http://www.clinicaltrials.gov) (December 5, 2007); Current Controlled Trials (http://controlled-trials.com/) (December 5, 2007), and Sistema de Información Esencial en Terapéutica y Salud (http://www.icf.uab.es/informacion/Papyrus/sietes.asp) (December 1, 2007). We also handsearched the European Haematology Association conference (June 2007), the American Society of Hematology conference (December 2007) and reference lists of all retrieved articles. We intended to include randomised clinical trials. We intended to summarise data by standard Cochrane Collaboration methodologies. We could not find any randomised clinical trials on interventions (packed red cell transfusion, oxygen therapy, fluid replacement therapy, analgesic drugs, and steroids) for the treatment of painful sickle cell crisis during pregnancy. This review found no randomised clinical trials on the safety and efficacy of interventions for treating painful sickle cell crisis during pregnancy. The effects of interventions need to be tested in randomised clinical trials.

Weight reduction for non-alcoholic fatty liver disease.

PubMed

Peng, Lijun; Wang, Jiyao; Li, Feng

2011-06-15

Non-alcoholic fatty liver disease (NAFLD) is becoming a wide spread liver disease. The present recommendations for treatment are not evidence-based. Some of them are various weight reduction measures with diet, exercise, drug, or surgical therapy. To assess the benefits and harms of intended weight reduction for patients with NAFLD. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, PubMed, EMBASE, Science Citation Index Expanded, Chinese Biomedicine Database, and ClinicalTrials.gov until February 2011. We included randomised clinical trials evaluating weight reduction with different measures versus no intervention or placebo in NAFLD patients. We extracted data independently. We calculated the odds ratio (OR) for dichotomous data and calculated the mean difference (MD) for continuous data, both with 95% confidence intervals (CI). The review includes seven trials; five on aspects of lifestyle changes (eg, diet, physical exercise) and two on treatment with a weight reduction drug 'orlistat'. In total, 373 participants were enrolled, and the duration of the trials ranged from 1 month to 1 year. Only one trial on lifestyle programme was judged to be of low risk of bias. We could not perform meta-analyses for the main outcomes as they were either not reported or there were insufficient number of trials for each outcome to be meta-analysed. We could meta-analyse the available data for body weight and body mass index only. Adverse events were poorly reported. The sparse data and high risk of bias preclude us from drawing any definite conclusion on lifestyle programme or orlistat for treatment of NAFLD. Further randomised clinical trials with low risk of bias are needed to test the beneficial and harmful effects of weight reduction for NAFLD patients. The long-term prognosis of development of fibrosis, mortality, and quality of life should be studied.

The impact of advertising patient and public involvement on trial recruitment: embedded cluster randomised recruitment trial.

PubMed

Hughes-Morley, Adwoa; Hann, Mark; Fraser, Claire; Meade, Oonagh; Lovell, Karina; Young, Bridget; Roberts, Chris; Cree, Lindsey; More, Donna; O'Leary, Neil; Callaghan, Patrick; Waheed, Waquas; Bower, Peter

2016-12-08

Patient and public involvement in research (PPIR) may improve trial recruitment rates, but it is unclear how. Where trials use PPIR to improve design and conduct, many do not communicate this clearly to potential participants. Better communication of PPIR might encourage patient enrolment, as trials may be perceived as more socially valid, relevant and trustworthy. We aimed to evaluate the impact on recruitment of directly advertising PPIR to potential trial participants. This is a cluster trial, embedded within a host trial ('EQUIP') recruiting service users diagnosed with severe mental illness. The intervention was informed by a systematic review, a qualitative study, social comparison theory and a stakeholder workshop including service users and carers. Adopting Participatory Design approaches, we co-designed the recruitment intervention with PPIR partners using a leaflet to advertise the PPIR in EQUIP and sent potential participants invitations with the leaflet (intervention group) or not (control group). Primary outcome was the proportion of patients enrolled in EQUIP. Secondary outcomes included the proportions of patients who positively responded to the trial invitation. Thirty-four community mental health teams were randomised and 8182 service users invited. For the primary outcome, 4% of patients in the PPIR group were enrolled versus 5.3% of the control group. The intervention was not effective for improving recruitment rates (adjusted OR = 0.75, 95% CI = 0.53 to 1.07, p = 0.113). For the secondary outcome of positive response, the intervention was not effective, with 7.3% of potential participants in the intervention group responding positively versus 7.9% of the control group (adjusted OR = 0.74, 95% CI = 0.53 to 1.04, p = 0.082). We did not find a positive impact of directly advertising PPIR on any other outcomes. To our knowledge, this is the largest ever embedded trial to evaluate a recruitment or PPIR intervention. Advertising PPIR did not improve enrolment rates or any other outcome. It is possible that rather than advertising PPIR being the means to improve recruitment, PPIR may have an alternative impact on trials by making them more attractive, acceptable and patient-centred. We discuss potential reasons for our findings and implications for recruitment practice and research. ISRCTN, ISRCTN16488358 . Registered on 14 May 2014. Study Within A Trial, SWAT-26 . Registered on 21 January 2016.

Photorefractive keratectomy (PRK) versus laser assisted in situ keratomileusis (LASIK) for hyperopia correction.

PubMed

Settas, George; Settas, Clare; Minos, Evangelos; Yeung, Ian Yl

2012-06-13

Hyperopia, or hypermetropia (also known as long-sightedness or far-sightedness), is the condition where the unaccommodating eye brings parallel light to a focus behind the retina instead of on it. Hyperopia can be corrected with both non-surgical and surgical methods, among them photorefractive keratectomy (PRK) and laser assisted In situ keratomileusis (LASIK). There is uncertainty as to whether hyperopic-PRK or hyperopic-LASIK is the better method. The objectives of this review were to determine whether PRK or LASIK leads to more reliable, stable and safe results when correcting a hyperopic refractive error. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 2), MEDLINE (January 1950 to February 2012), EMBASE (January 1980 to February 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to February 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 17 February 2012. When trials are included in the review we will search the reference lists of the studies included in the review for information about further trials. We will use the Science Citation Index to search for papers that cite any studies included in this review. We did not handsearch journals or conference proceedings specifically for this review. We planned to include only randomised controlled trials (RCTs) comparing PRK against LASIK for correction of hyperopia and then perform a sensitivity analysis of pre- and post-millennial trials since this is the mid-point in the history of both PRK and LASIK. We did not identify any studies that met the inclusion criteria for this review. As no studies met the inclusion criteria for this review, we discussed the results of non-randomised trials comparing hyperopic-PRK with hyperopic-LASIK. No robust, reliable conclusions could be reached, but the non-randomised trials reviewed appear to be in agreement that hyperopic-PRK and hyperopic-LASIK are of comparable efficacy. High quality, well-planned open RCTs are needed in order to obtain a robust clinical evidence base.

Complementary and alternative therapies for pain management in labour.

PubMed

Smith, C A; Collins, C T; Cyna, A M; Crowther, C A

2006-10-18

Many women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute towards the popularity of complementary methods of pain management. This review examined currently available evidence supporting the use of alternative and complementary therapies for pain management in labour. To examine the effects of complementary and alternative therapies for pain management in labour on maternal and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to February 2006), EMBASE (1980 to February 2006) and CINAHL (1980 to February 2006). The inclusion criteria included published and unpublished randomised controlled trials comparing complementary and alternative therapies (but not biofeedback) with placebo, no treatment or pharmacological forms of pain management in labour. All women whether primiparous or multiparous, and in spontaneous or induced labour, in the first and second stage of labour were included. Meta-analysis was performed using relative risks for dichotomous outcomes and mean differences for continuous outcomes. The outcome measures were maternal satisfaction, use of pharmacological pain relief and maternal and neonatal adverse outcomes. Fourteen trials were included in the review with data reporting on 1537 women using different modalities of pain management; 1448 women were included in the meta-analysis. Three trials involved acupuncture (n = 496), one audio-analgesia (n = 24), two trials acupressure (n = 172), one aromatherapy (n = 22), five trials hypnosis (n = 729), one trial of massage (n = 60), and relaxation (n = 34). The trials of acupuncture showed a decreased need for pain relief (relative risk (RR) 0.70, 95% confidence interval (CI) 0.49 to 1.00, two trials 288 women). Women taught self-hypnosis had decreased requirements for pharmacological analgesia (RR 0.53, 95% CI 0.36 to 0.79, five trials 749 women) including epidural analgesia (RR 0.30, 95% CI 0.22 to 0.40) and were more satisfied with their pain management in labour compared with controls (RR 2.33, 95% CI 1.15 to 4.71, one trial). No differences were seen for women receiving aromatherapy, or audio analgesia. Acupuncture and hypnosis may be beneficial for the management of pain during labour; however, the number of women studied has been small. Few other complementary therapies have been subjected to proper scientific study.

Published intimate partner violence studies often differ from their trial registration records.

PubMed

Madden, Kim; Tai, Kerry; Ali, Zak; Schneider, Patricia; Singh, Mahip; Ghert, Michelle; Bhandari, Mohit

2017-12-27

Registering study protocols in a trial registry is important for methodologic transparency and reducing selective reporting bias. The objective of this investigation was to determine whether published studies of intimate partner violence (IPV) that had been registered matched the registration record on key study design elements. We systematically searched three trial registries to identify registered IPV studies and the published literature for the associated publication. Two authors independently determined for each study whether key study elements in the registry matched those in the published paper. We included 66 studies published between 2006 and 2017. Nearly half (29/66, 44%) were registered after study completion. Many (26/66, 39%) had discrepancies regarding the primary outcome, and nearly two-thirds (42/66, 64%) had discrepancies in secondary outcomes. Discrepancies in study design were less frequent (13/66, 20%). However, large changes in sample size (26/66, 39%) and discrepancies in funding source (28/66, 42%) were frequently observed. Trial registries are important tools for research transparency and identifying and preventing outcome switching and selective outcome reporting bias. Published IPV studies often differ from their records in trial registries. Researchers should pay close attention to the accuracy of trial registry records.

Artesunate plus pyronaridine for treating uncomplicated Plasmodium falciparum malaria.

PubMed

Bukirwa, Hasifa; Unnikrishnan, B; Kramer, Christine V; Sinclair, David; Nair, Suma; Tharyan, Prathap

2014-03-04

The World Health Organization (WHO) recommends that people with uncomplicated Plasmodium falciparum malaria are treated using Artemisinin-based Combination Therapy (ACT). ACT combines three-days of a short-acting artemisinin derivative with a longer-acting antimalarial which has a different mode of action. Pyronaridine has been reported as an effective antimalarial over two decades of use in parts of Asia, and is currently being evaluated as a partner drug for artesunate. To evaluate the efficacy and safety of artesunate-pyronaridine compared to alternative ACTs for treating people with uncomplicated P. falciparum malaria. We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; ClinicalTrials.gov; the metaRegister of Controlled Trials (mRCT); and the WHO International Clinical Trials Search Portal up to 16 January 2014. We searched reference lists and conference abstracts, and contacted experts for information about ongoing and unpublished trials. Randomized controlled trials of artesunate-pyronaridine versus other ACTs in adults and children with uncomplicated P. falciparum malaria.For the safety analysis, we also included adverse events data from trials comparing any treatment regimen containing pyronaridine with regimens not containing pyronaridine. Two authors independently assessed trial eligibility and risk of bias, and extracted data. We combined dichotomous data using risk ratios (RR) and continuous data using mean differences (MD), and presented all results with a 95% confidence interval (CI). We used the GRADE approach to assess the quality of evidence. We included six randomized controlled trials enrolling 3718 children and adults. Artesunate-pyronaridine versus artemether-lumefantrineIn two multicentre trials, enrolling mainly older children and adults from west and south-central Africa, both artesunate-pyronaridine and artemether-lumefantrine had fewer than 5% PCR adjusted treatment failures during 42 days of follow-up, with no differences between groups (two trials, 1472 participants, low quality evidence). There were fewer new infections during the first 28 days in those given artesunate-pyronaridine (PCR-unadjusted treatment failure: RR 0.60, 95% CI 0.40 to 0.90, two trials, 1720 participants, moderate quality evidence), but no difference was detected over the whole 42 day follow-up (two trials, 1691 participants, moderate quality evidence). Artesunate-pyronaridine versus artesunate plus mefloquineIn one multicentre trial, enrolling mainly older children and adults from South East Asia, both artesunate-pyronaridine and artesunate plus mefloquine had fewer than 5% PCR adjusted treatment failures during 28 days follow-up (one trial, 1187 participants, moderate quality evidence). PCR-adjusted treatment failures were 6% by day 42 for these treated with artesunate-pyronaridine, and 4% for those with artesunate-mefloquine (RR 1.64, 95% CI 0.89 to 3.00, one trial, 1116 participants, low quality evidence). Again, there were fewer new infections during the first 28 days in those given artesunate-pyronaridine (PCR-unadjusted treatment failure: RR 0.35, 95% CI 0.17 to 0.73, one trial, 1720 participants, moderate quality evidence), but no differences were detected over the whole 42 days (one trial, 1146 participants, low quality evidence). Adverse effectsSerious adverse events were uncommon in these trials, with no difference detected between artesunate-pyronaridine and comparator ACTs. The analysis of liver function tests showed biochemical elevation were four times more frequent with artesunate-pyronaridine than with the other antimalarials (RR 4.17, 95% CI 1.38 to 12.62, four trials, 3523 participants, moderate quality evidence). Artesunate-pyronaridine performed well in these trials compared to artemether-lumefantrine and artesunate plus mefloquine, with PCR-adjusted treatment failure at day 28 below the 5% standard set by the WHO. Further efficacy and safety studies in African and Asian children are required to clarify whether this combination is an option for first-line treatment.

WITHDRAWN: Resorbable versus titanium plates for facial fractures.

PubMed

Dorri, Mojtaba; Oliver, Richard

2018-05-23

Rigid internal fixation of the jaw bones is a routine procedure for the management of facial fractures. Titanium plates and screws are routinely used for this purpose. The limitations of this system has led to the development of plates manufactured from bioresorbable materials which, in some cases, omits the necessity for the second surgery. However, concerns remain about the stability of fixation and the length of time required for their degradation and the possibility of foreign body reactions. To compare the effectiveness of bioresorbable fixation systems with titanium systems for the management of facial fractures. We searched the following databases: The Cochrane Oral Health Group's Trials Register (to 20th August 2008), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to 20th August 2008), EMBASE (from 1980 to 20th August 2008), http://www.clinicaltrials.gov/ and http://www.controlled-trials.com (to 20th August 2008). Randomised controlled trials comparing resorbable versus titanium fixation systems used for facial fractures. Retrieved studies were independently screened by two review authors. Results were to be expressed as random-effects models using mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals. Heterogeneity was to be investigated including both clinical and methodological factors. The search strategy retrieved 53 potentially eligible studies. None of the retrieved studies met our inclusion criteria and all were excluded from this review. One study is awaiting classification as we failed to obtain the full text copy. Three ongoing trials were retrieved, two of which were stopped before recruiting the planned number of participants. In one study, the excess complications in the resorbable arm was declared as the reason for stopping the trial. This review illustrates that there are no published randomised controlled clinical trials relevant to this review question. There is currently insufficient evidence for the effectiveness of resorbable fixation systems compared with conventional titanium systems for facial fractures. The findings of this review, based on the results of the aborted trials, do not suggest that resorbable plates are as effective as titanium plates. In future, the results of ongoing clinical trials may provide high level reliable evidence for assisting clinicians and patients for decision making. Trialists should design their studies accurately and comprehensively to meet the aims and objectives defined for the study.

A Cluster Randomised Trial Introducing Rapid Diagnostic Tests into Registered Drug Shops in Uganda: Impact on Appropriate Treatment of Malaria.

PubMed

Mbonye, Anthony K; Magnussen, Pascal; Lal, Sham; Hansen, Kristian S; Cundill, Bonnie; Chandler, Clare; Clarke, Siân E

2015-01-01

Inappropriate treatment of malaria is widely reported particularly in areas where there is poor access to health facilities and self-treatment of fevers with anti-malarial drugs bought in shops is the most common form of care-seeking. The main objective of the study was to examine the impact of introducing rapid diagnostic tests for malaria (mRDTs) in registered drug shops in Uganda, with the aim to increase appropriate treatment of malaria with artemisinin-based combination therapy (ACT) in patients seeking treatment for fever in drug shops. A cluster-randomized trial of introducing mRDTs in registered drug shops was implemented in 20 geographical clusters of drug shops in Mukono district, central Uganda. Ten clusters were randomly allocated to the intervention (diagnostic confirmation of malaria by mRDT followed by ACT) and ten clusters to the control arm (presumptive treatment of fevers with ACT). Treatment decisions by providers were validated by microscopy on a reference blood slide collected at the time of consultation. The primary outcome was the proportion of febrile patients receiving appropriate treatment with ACT defined as: malaria patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving ACT or rectal artesunate, and patients with no malaria parasites not given ACT. A total of 15,517 eligible patients (8672 intervention and 6845 control) received treatment for fever between January-December 2011. The proportion of febrile patients who received appropriate ACT treatment was 72·9% versus 33·7% in the control arm; a difference of 36·1% (95% CI: 21·3 - 50·9), p<0·001. The majority of patients with fever in the intervention arm accepted to purchase an mRDT (97·8%), of whom 58·5% tested mRDT-positive. Drug shop vendors adhered to the mRDT results, reducing over-treatment of malaria by 72·6% (95% CI: 46·7- 98·4), p<0·001) compared to drug shop vendors using presumptive diagnosis (control arm). Diagnostic testing with mRDTs compared to presumptive treatment of fevers implemented in registered drug shops substantially improved appropriate treatment of malaria with ACT. ClinicalTrials.gov NCT01194557.

Use of placebo controls in the evaluation of surgery: systematic review

PubMed Central

Judge, Andrew; Hopewell, Sally; Collins, Gary S; Dean, Benjamin J F; Rombach, Ines; Brindley, David; Savulescu, Julian; Beard, David J; Carr, Andrew J

2014-01-01

Objective To investigate whether placebo controls should be used in the evaluation of surgical interventions. Design Systematic review. Data sources We searched Medline, Embase, and the Cochrane Controlled Trials Register from their inception to November 2013. Study selection Randomised clinical trials comparing any surgical intervention with placebo. Surgery was defined as any procedure that both changes the anatomy and requires a skin incision or use of endoscopic techniques. Data extraction Three reviewers (KW, BJFD, IR) independently identified the relevant trials and extracted data on study details, outcomes, and harms from included studies. Results In 39 out of 53 (74%) trials there was improvement in the placebo arm and in 27 (51%) trials the effect of placebo did not differ from that of surgery. In 26 (49%) trials, surgery was superior to placebo but the magnitude of the effect of the surgical intervention over that of the placebo was generally small. Serious adverse events were reported in the placebo arm in 18 trials (34%) and in the surgical arm in 22 trials (41.5%); in four trials authors did not specify in which arm the events occurred. However, in many studies adverse events were unrelated to the intervention or associated with the severity of the condition. The existing placebo controlled trials investigated only less invasive procedures that did not involve laparotomy, thoracotomy, craniotomy, or extensive tissue dissection. Conclusions Placebo controlled trial is a powerful, feasible way of showing the efficacy of surgical procedures. The risks of adverse effects associated with the placebo are small. In half of the studies, the results provide evidence against continued use of the investigated surgical procedures. Without well designed placebo controlled trials of surgery, ineffective treatment may continue unchallenged. PMID:24850821

Trials with patient-reported outcomes registered on the Australian New Zealand Clinical Trials Registry (ANZCTR).

PubMed

Mercieca-Bebber, Rebecca; Williams, Douglas; Tait, Margaret-Ann; Roydhouse, Jessica; Busija, Lucy; Sundaram, Chindhu Shunmuga; Wilson, Michelle; Langford, Ailsa; Rutherford, Claudia; Roberts, Natasha; King, Madeleine; Vodicka, Elisabeth; Devine, Beth

2018-06-18

It is important to understand the number, types and regions of trials that include patient-reported outcomes (PROs) to appreciate how patient experiences have been considered in studies of health and interventions. Twenty-seven percent of trials registered with ClinicalTrials.gov (2007-2013) included PROs; however, a regional breakdown was not provided and no reviews have been conducted of the Australia New Zealand Clinical Trials Registry (ANZCTR). We aimed to identify trials registered with ANZCTR with PRO endpoints and describe their characteristics. ANZCTR was systematically searched from inception (2005) to 31 March 2017 for trials with PRO endpoints. Search terms included PRO measures listed in Patient-Reported Outcomes Quality of Life Instrument Database and Grid-Enabled Measures, as well as generic PRO terms (e.g. "quality of life" (QOL)). Trial endpoints were individually coded using an established framework to identify trials with PROs for the analysis. Of 13,666 registered trials, 6168 (45.1%) included a PRO. The proportion of studies including PROs increased between 2006 and 2016 (r = 0.74, p = 0.009). Among the 6168 trials, there were 17,961 individual PRO endpoints, including symptoms/functional outcomes/condition-specific QOL (65.6%), generic QOL (13.2%), patient-reported experiences (9.9%), patient-reported behaviours (7.9%). Mental health was the most common category (99.8% included PROs), followed by physical medicine/rehabilitation (65.6%), musculoskeletal (63.5%), public health (63.1%), and cancer (54.2%). Our findings suggest growing use of PROs in the assessment of health and interventions in ANZ. Our review identifies trial categories with limited patient-reported information and provides a basis for future work on the impact of PRO findings in clinical care.

Surgical interventions for high grade vulval intraepithelial neoplasia

PubMed Central

Kaushik, Sonali; Pepas, Litha; Nordin, Andy; Bryant, Andrew; Dickinson, Heather O

2014-01-01

Background Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin. This uncommon chronic skin condition of the vulva is associated with a high risk of recurrence and the potential to progress to vulval cancer. The condition is complicated by its’ multicentric and multifocal nature. The incidence of this condition appears to be rising particularly in the younger age group. There is a lack of consensus on the optimal surgical treatment method. However, the rationale for surgical treatment of VIN has been to treat symptoms and exclude underlying malignancy with the continued aim of preservation of vulval anatomy and function. Repeated treatments affect local cosmesis and cause psychosexual morbidity thus impacting on the patients’ quality of life. Objectives To evaluate the effectiveness and safety of surgical interventions for high grade VIN. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 3, 2010, Cochrane Gynaecological Cancer Group Trials Register, MEDLINE and EMBASE up to September 2010. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that compared surgical interventions, in adult women diagnosed with high grade vulval intraepithelial neoplasia. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Main results We found only one RCT which included 30 women that met our inclusion criteria and this trial reported data on carbon dioxide laser (CO2 laser) versus ultrasonic surgical aspiration (USA). There was no statistically significant difference in the risk of disease recurrence after one year follow-up, pain, presence of scarring, dysuria or burning, adhesions, infection, abnormal discharge and eschar between women who received CO2 laser and those who received USA. The trial lacked statistical power due to the small number of women in each group and the low number of observed events, but was at low risk of bias. Authors’ conclusions The included trial lacked statistical power due to the small number of women in each group and the low number of observed events. Therefore in the absence of reliable evidence regarding the effectiveness and safety of the two surgical techniques for the management of vulval intraepithelial neoplasia precludes any definitive guidance or recommendations for clinical practice. PMID:21249698

The effects of immunotherapy with intravenous immunoglobulins versus no intervention, placebo, or usual care in patients with recurrent miscarriages: a protocol for a systematic review with meta-analyses, trial sequential analyses, and individual patient data meta-analyses of randomised clinical trials.

PubMed

Egerup, Pia; Lindschou, Jane; Gluud, Christian; Christiansen, Ole Bjarne

2014-08-15

Recurrent miscarriage is generally defined as three or more miscarriages before gestational week 20. Recurrent miscarriage affects 1% of all women and the condition can only be explained by parental chromosome abnormalities, uterine malformations, or endocrine or thrombophilic disturbances to a limited extent. Immunological disturbances are hypothesised to play an important role in recurrent miscarriage and, therefore, various types of immunologically-based therapies have been tested in recurrent miscarriage patients including intravenous immunoglobulins. So far, at least eight randomised placebo-controlled trials, with opposing results, investigating intravenous immunoglobulins with a total of 324 recurrent miscarriage patients have been published. We will include randomised clinical trials irrespective of publication date, publication type, publication language, and publication status investigating infusions with immunoglobulins in relation to pregnancy compared to placebo, no intervention, or treatment as usual for assessments of benefits and harms. The relevant published literature will be searched using the following databases: Cochrane Central Register of Controlled Trials, Medline, Embase, WHO International Clinical Trials Registry Platform, and Ovid Medline In-Process and Other Non-Indexed Citations databases. Two review authors will independently extract data and assess risk of bias. We will undertake meta-analyses according to the recommendations stated in the Cochrane Handbook for Systematic Reviews of Interventions. Further, we will conduct trial sequential analyses and individual patient data meta-analyses. A miscarriage results in great sorrow, loss of life quality, and personal concern. In particular, recurrent miscarriage is extremely stressful and burdensome. It is, therefore, very important to conduct research in this area. There is currently no evidence-based treatment for women with recurrent miscarriage which significantly improves their ability to give live birth. Therefore, a comprehensive up-to-date systematic review is needed. By using individual patient data, it will be possible to provide new knowledge about the benefits and harms of intravenous immunoglobulins and try to identify the subgroup in which the treatment will have the highest impact.This systematic review protocol was registered within the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42014007112.

Effects of propranolol on fear of dental extraction: study protocol for a randomized controlled trial.

PubMed

Steenen, Serge A; van Wijk, Arjen J; van Westrhenen, Roos; de Lange, Jan; de Jongh, Ad

2015-11-25

Undergoing an extraction has been shown to pose a significantly increased risk for the development of chronic apprehension for dental surgical procedures, disproportionate forms of dental anxiety (that is, dental phobia), and symptoms of post-traumatic stress. Evidence suggests that intrusive emotional memories of these events both induce and maintain these forms of anxiety. Addressing these problems effectively requires an intervention that durably reduces both the intrusiveness of key fear-related memories and state anxiety during surgery. Moreover, evidence suggests that propranolol is capable of inhibiting "memory reconsolidation" (that is, it blocks the process of storing a recently retrieved fear memory). Hence, the purpose of this trial is to determine the anxiolytic and fear memory reconsolidation inhibiting effects of the ß-adrenoreceptor antagonist propranolol on patients with high levels of fear in anticipation of a dental extraction. This trial is designed as a multicenter, randomized, placebo-controlled, two-group, parallel, double-blind trial of 34 participants. Consecutive patients who have been referred by their dentist to the departments of oral and maxillofacial surgery of a University hospital or a secondary referral hospital in the Netherlands for at least two tooth and/or molar removals and with self-reported high to extreme fear in anticipation of a dental extraction will be recruited. The intervention is the administration of two 40 mg propranolol capsules 1 hour prior to a dental extraction, followed by one 40 mg capsule directly postoperatively. Placebo capsules will be used as a comparator. The primary outcome will be dental trait anxiety score reduction from baseline to 4-weeks follow-up. The secondary outcomes will be self-reported anxiety during surgery, physiological parameters (heart rate and blood pressure) during recall of the crucial fear-related memory, self-reported vividness, and emotional charge of the crucial fear-related memory. This randomized trial is the first to test the efficacy of 120 mg of perioperative propranolol versus placebo in reducing short-term ("state") anxiety during dental extraction, fear memory reconsolidation, and lasting dental ("trait") anxiety in a clinical population. If the results show a reduction in anxiety, this would offer support for routinely prescribing propranolol in patients who are fearful of undergoing dental extractions. ClinicalTrials.gov identifier: NCT02268357 , registered on 7 October 2014. The Netherlands National Trial Register identifier: NTR5364 , registered on 16 August 2015.

Cost-effective recruitment methods for a large randomised trial in people with diabetes: A Study of Cardiovascular Events iN Diabetes (ASCEND).

PubMed

Aung, Theingi; Haynes, Richard; Barton, Jill; Cox, Jolyon; Murawska, Aleksandra; Murphy, Kevin; Lay, Michael; Armitage, Jane; Bowman, Louise

2016-06-13

Clinical trials require cost-effective methods for identifying, randomising, and following large numbers of people in order to generate reliable evidence. ASCEND (A Study of Cardiovascular Events iN Diabetes) is a randomised '2 × 2 factorial design' study of aspirin and omega-3 fatty acid supplements for the primary prevention of cardiovascular events in people with diabetes; this study used central disease registers and a mail-based approach to identify, randomise, and follow 15,000 people. In collaboration with UK consultants and general practitioners (GPs), researchers identified potentially eligible people with diabetes from centrally held registers (e.g. for retinopathy screening) and GP-held disease registers. Permission was obtained under section 251 of the National Health Service Act 2006 (previously section 60 of the NHS act 2001) to allow invitation letters to be generated centrally in the name of the holder of the register. In addition, with the collaboration of the National Institutes for Health Research (NIHR) Diabetes and Primary Care Research Networks (DRN and PCRN), general practices sent pre-assembled invitation packs to people with a diagnosis of diabetes. Invitation packs included a cover letter, screening questionnaire (with consent form), information leaflet, and a Freepost envelope. Eligible patients entered a 2-month, pre-randomisation, run-in phase on placebo tablets and were only randomised if they completed a randomisation form and remained willing and eligible at the end of the run-in. Follow-up is ongoing, using mail-based approaches that are being supplemented by central registry data. Information on approximately 600,000 people listed on 58 centrally held diabetes registers was obtained, and 300,188 potentially eligible patients were invited to join the study. In addition, 785 GP practices mailed invitations to 120,875 patients. A further 2,340 potential study participants were identified via other routes. In total, 423,403 people with diabetes were invited to take part; 26,462 entered the 2-month, pre-randomisation, run-in phase; and 15,480 were randomised. If sufficient numbers of potentially eligible patients can be identified centrally and the trial treatments do not require participants to attend clinics, the recruitment and follow-up of patients by mail is feasible and cost-effective. Wider use of these methods could allow more, large, randomised trials to be undertaken successfully and cost-effectively. Current Controlled Trials, ISRCTN60635500 , registered on 14 July 2005.

Home exercise programmes supported by video and automated reminders compared with standard paper-based home exercise programmes in patients with stroke: a randomized controlled trial.

PubMed

Emmerson, Kellie B; Harding, Katherine E; Taylor, Nicholas F

2017-08-01

To determine whether patients with stroke receiving rehabilitation for upper limb deficits using smart technology (video and reminder functions) demonstrate greater adherence to prescribed home exercise programmes and better functional outcomes when compared with traditional paper-based exercise prescription. Randomized controlled trial comparing upper limb home exercise programmes supported by video and automated reminders on smart technology, with standard paper-based home exercise programmes. A community rehabilitation programme within a large metropolitan health service. Patients with stroke with upper limb deficits, referred for outpatient rehabilitation. Participants were randomly assigned to the control (paper-based home exercise programme) or intervention group (home exercise programme filmed on an electronic tablet, with an automated reminder). Both groups completed their prescribed home exercise programme for four weeks. The primary outcome was adherence using a self-reported log book. Secondary outcomes were change in upper limb function and patient satisfaction. A total of 62 participants were allocated to the intervention ( n = 30) and control groups ( n = 32). There were no differences between the groups for measures of adherence (mean difference 2%, 95% CI -12 to 17) or change in the Wolf Motor Function Test log transformed time (mean difference 0.02 seconds, 95% CI -0.1 to 0.1). There were no between-group differences in how participants found instructions ( p = 0.452), whether they remembered to do their exercises ( p = 0.485), or whether they enjoyed doing their exercises ( p = 0.864). The use of smart technology was not superior to standard paper-based home exercise programmes for patients recovering from stroke. This trial design was registered prospectively with the Australian and New Zealand Clinical Trials Register, ID: ACTRN 12613000786796. http://www.anzctr.org.au/trialSearch.aspx.

Antimicrobial drugs for treating cholera.

PubMed

Leibovici-Weissman, Ya'ara; Neuberger, Ami; Bitterman, Roni; Sinclair, David; Salam, Mohammed Abdus; Paul, Mical

2014-06-19

Cholera is an acute watery diarrhoea caused by infection with the bacterium Vibrio cholerae, which if severe can cause rapid dehydration and death. Effective management requires early diagnosis and rehydration using oral rehydration salts or intravenous fluids. In this review, we evaluate the additional benefits of treating cholera with antimicrobial drugs. To quantify the benefit of antimicrobial treatment for patients with cholera, and determine whether there are differences between classes of antimicrobials or dosing schedules. We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; African Index Medicus; LILACS; Science Citation Index; metaRegister of Controlled Trials; WHO International Clinical Trials Registry Platform; conference proceedings; and reference lists to March 2014. Randomized and quasi-randomized controlled clinical trials in adults and children with cholera that compared: 1) any antimicrobial treatment with placebo or no treatment; 2) different antimicrobials head-to-head; or 3) different dosing schedules or different durations of treatment with the same antimicrobial. Two reviewers independently applied inclusion and exclusion criteria, and extracted data from included trials. Diarrhoea duration and stool volume were defined as primary outcomes. We calculated mean difference (MD) or ratio of means (ROM) for continuous outcomes, with 95% confidence intervals (CI), and pooled data using a random-effects meta-analysis. The quality of evidence was assessed using the GRADE approach. Thirty-nine trials were included in this review with 4623 participants. Antimicrobials versus placebo or no treatment Overall, antimicrobial therapy shortened the mean duration of diarrhoea by about a day and a half compared to placebo or no treatment (MD -36.77 hours, 95% CI -43.51 to -30.03, 19 trials, 1013 participants, moderate quality evidence). Antimicrobial therapy also reduced the total stool volume by 50% (ROM 0.5, 95% CI 0.45 to 0.56, 18 trials, 1042 participants, moderate quality evidence) and reduced the amount of rehydration fluids required by 40% (ROM 0.60, 95% CI 0.53 to 0.68, 11 trials, 1201 participants, moderate quality evidence). The mean duration of fecal excretion of vibrios was reduced by almost three days (MD 2.74 days, 95% CI -3.07 to -2.40, 12 trials, 740 participants, moderate quality evidence).There was substantial heterogeneity in the size of these benefits, probably due to differences in the antibiotic used, the trial methods (particularly effective randomization), and the timing of outcome assessment. The benefits of antibiotics were seen both in trials recruiting only patients with severe dehydration and in those recruiting patients with mixed levels of dehydration. Comparisons of antimicrobials In head-to-head comparisons, there were no differences detected in diarrhoea duration or stool volume for tetracycline compared to doxycycline (three trials, 230 participants, very low quality evidence); or tetracycline compared to ciprofloxacin or norfloxacin (three trials, 259 participants, moderate quality evidence). In indirect comparisons with substantially more trials, tetracycline appeared to have larger benefits than doxycycline, norfloxacin and trimethoprim-sulfamethoxazole for the primary review outcomes.Single dose azithromycin shortened the duration of diarrhoea by over a day compared to ciprofloxacin (MD -32.43, 95% CI -62.90 to -1.95, two trials, 375 participants, moderate quality evidence) and by half a day compared to erythromycin (MD -12.05, 95% CI -22.02 to -2.08, two trials, 179 participants, moderate quality evidence). It was not compared with tetracycline. In treating cholera, antimicrobials result in substantial improvements in clinical and microbiological outcomes, with similar effects observed in severely and non-severely ill patients. Azithromycin and tetracycline may have some advantages over other antibiotics.

Tafenoquine for preventing relapse in people with Plasmodium vivax malaria.

PubMed

Rajapakse, Senaka; Rodrigo, Chaturaka; Fernando, Sumadhya Deepika

2015-04-29

Plasmodium vivax malaria is widespread, and the persistent liver stage causes relapse of the disease which contributes to continued P. vivax transmission. Primaquine is currently the only drug that cures the parasite liver stage, but requires 14 days to be effective and can cause haemolysis in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In addition, there is some evidence of parasite resistance to the drug. Tafenoquine is a new alternative with a longer half-life. To assess the effects of tafenoquine in people with P. vivax infection. We searched the following databases up to 13 April 2015: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; CINAHL; SCOPUS; and LILACS. We also searched the World Health Organization (WHO) International Clinical Trial Registry Platform and the metaRegister of Controlled Trials (mRCT) for ongoing trials using "tafenoquine" and "malaria" as search terms up to 13 April 2015. Randomized controlled trials (RCTs) in people with P. vivax malaria. Adverse effects of tafenoquine are assessed in populations where people with G6PD deficiency have been excluded, and in populations without screening for G6PD deficiency. All review authors independently extracted data and assessed trial quality. Meta-analysis was carried out where appropriate, and estimates given as relative risk with 95% confidence intervals. We assessed the quality of the evidence using the GRADE approach. Three RCTs met our inclusion criteria, with the asexual infection in both the tafenoquine and comparator arm treated with chloroquine, and in all trials G6PD deficiency patients were excluded. Tafenoquine dose comparisonsThree of the included trials compared eight different dosing regimens. Tafenoquine doses of 300 mg and above resulted in fewer relapses than no hypnozoite treatment over six months follow-up in adults (300 mg single dose: RR 0.19, 95% CI 0.08 to 0.41, one trial, 110 participants, moderate quality evidence; 500 to 600 mg single dose: RR 0.14, 95%CI 0.06 to 0.34, two trials, 122 participants, moderate quality evidence; 1800 mg to 3000 mg in divided doses: RR 0.05, 95% CI 0.01 to 0.23, two trials, 63 participants, low quality evidence).In people with normal G6PD status, there may be little or no difference in serious adverse events (three trials, 358 participants, low quality evidence); or any adverse event (one trial, 272 participants, low quality evidence). Tafenoquine versus primaquine Two of the included trials compared four different dosing regimens of tafenoquine against the standard primaquine regimen of 15 mg/day for 14 days. A single tafenoquine dose of 600 mg may be more effective than primaquine in relation to relapses at six months follow-up (RR 0.29, 95% CI 0.10 to 0.84, two trials, 98 participants, low quality evidence)In people with normal G6PD status, there may be little or no difference for serious adverse events (two trials, 323 participants, low quality evidence) or any adverse event (two trials, 323 participants, low quality evidence) between tafenoquine and primaquine. Tafenoquine prevents relapses after clinically and parasitologically confirmed P. vivax malaria. The drug is untested in pregnancy, children and in G6PD-deficient people. The shorter treatment course is an important practical advantage in people who do not have G6PD deficiency, but the longer half-life may have more substantive consequences if given inadvertently to people with G6PD deficiency.

Social capital interventions targeting older people and their impact on health: a systematic review.

PubMed

Coll-Planas, Laura; Nyqvist, Fredrica; Puig, Teresa; Urrútia, Gerard; Solà, Ivan; Monteserín, Rosa

2017-07-01

Observational studies show that social capital is a protective health factor. Therefore, we aim to assess the currently unclear health impact of social capital interventions targeting older adults. We conducted a systematic review based on a logic model. Studies published between January 1980 and July 2015 were retrieved from MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Central Register of Controlled Trials and Web of Science. We included randomised controlled trials targeting participants over 60 years old and focused on social capital or its components (eg, social support and social participation). The comparison group should not promote social capital. We assessed risk of bias and impact on health outcomes and use of health-related resources applying a procedure from the Canadian Agency for Drugs and Technologies in Health (CADTH) based on vote-counting and standardised decision rules. The review protocol was registered in PROSPERO (reference number CRD42014015362). We examined 17 341 abstracts and included 73 papers reporting 36 trials. Trials were clinically and methodologically diverse and reported positive effects in different contexts, populations and interventions across multiple subjective and objective measures. According to sufficiently reported outcomes, social capital interventions showed mixed effects on quality of life, well-being and self-perceived health and were generally ineffective on loneliness, mood and mortality. Eight trials with high quality showed favourable impacts on overall, mental and physical health, mortality and use of health-related resources. Our review highlights the lack of evidence and the diversity among trials, while supporting the potential of social capital interventions to reach comprehensive health effects in older adults. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Prophylactic versus therapeutic amnioinfusion for oligohydramnios in labour.

PubMed

Hofmeyr, G J

2000-01-01

Amnioinfusion aims to relieve umbilical cord compression during labour by infusing a liquid into the uterine cavity. The objective of this review was to assess the effects of prophylactic amnioinfusion for oligohydramnios compared with therapeutic amnioinfusion only if fetal heart rate decelerations or thick meconium-staining of the liquor occur. The Cochrane Pregnancy and Childbirth Group trials register and Cochrane Controlled Trials Register were searched. Date of last search: October 1997. Randomised trials comparing prophylactic with therapeutic amnioinfusion in women with oligohydramnios but not fetal heart rate deceleration in labour. The reviewer assessed trial quality and extracted data. Two studies of 285 women were included. No differences were found in the rate of caesarean section (relative risk 0.98, 95% confidence interval 0.58 to 1.66), or forceps delivery. There were no difference in Apgar scores, cord arterial pH, oxytocin augmentation, meconium aspiration, neonatal pneumonia or postpartum endometritis. Prophylactic amnioinfusion was associated with increased intrapartum fever (relative risk 3.48, 95% confidence interval 1.21 to 10.05). There appears to be no advantage of prophylactic amnioinfusion over therapeutic amnioinfusion carried out only when fetal heart rate decelerations or thick meconium-staining of the liquor occur.

Interventions for vaginismus.

PubMed

Melnik, Tamara; Hawton, Keith; McGuire, Hugh

2012-12-12

Vaginismus is an involuntary contraction of the vaginal muscles which makes sexual intercourse difficult or impossible. It is one of the more common female psychosexual problems. Various therapeutic strategies for vaginismus, such as sex therapy and desensitisation, have been proposed, and uncontrolled case series appear promising. To assess the effects of different interventions for vaginismus. We searched the Cochrane Depression, Anxiety and Neurosis Group's Specialised Register (CCDANCTR-Studies and CCDANCTR-References) to August 2012. This register contains relevant randomised controlled trials from: The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). We searched reference lists and conference abstracts. We contacted experts in the field regarding unpublished material. Controlled trials comparing treatments for vaginismus with another treatment, a placebo treatment, treatment as usual or waiting list control. The review authors extracted data which we verified with the trial investigator where possible. Five studies were included, of which four with a total of 282 participants provided data. No meta-analysis was possible due to heterogeneity of comparisons within included studies as well as inadequate reporting of data. All studies were considered to be at either moderate or high risk of bias. The results of this systematic review indicate that there is no clinical or statistical difference between systematic desensitisation and any of the control interventions (either waiting list control, systematic desensitisation combined with group therapy or in vitro (with women under instruction by the therapist) desensitisation) for the treatment of vaginismus. The drop-out rates were higher in the waiting list groups. A clinically relevant effect of systematic desensitisation when compared with any of the control interventions cannot be ruled out. None of the included trials compared other behaviour therapies (e.g. cognitive behaviour therapy, sex therapy) to pharmacological interventions. The findings are limited by the evidence available and as such conclusions about the efficacy of interventions for the treatment of vaginismus should be drawn cautiously.

Moderate quality evidence finds statistical benefit in oral health for powered over manual toothbrushes.

PubMed

Niederman, Richard

2014-09-01

The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CINAHL, National Institutes of Health Trials Register and the WHO Clinical Trials Registry Platform for ongoing trials. Reference lists of identified articles were also scanned for relevant papers. Identified manufacturers were contacted for additional information. Only randomised controlled trials comparing manual and powered toothbrushes were considered. Crossover trials were eligible for inclusion if the wash-out period length was more than two weeks. Study assessment and data extraction were carried out independently by at least two reviewers. The primary outcome measures were quantified levels of plaque or gingivitis. Risk of bias assessment was undertaken. Standard Cochrane methodological approaches were taken. Random-effects models were used provided there were four or more studies included in the meta-analysis, otherwise fixed-effect models were used. Data were classed as short term (one to three months) and long term (greater than three months). Fifty-six trials were included with 51 (4624 patients) providing data for meta-analysis. The majority (46) were at unclear risk of bias, five at high risk of bias and five at low risk. There was moderate quality evidence that powered toothbrushes provide a statistically significant benefit compared with manual toothbrushes with regard to the reduction of plaque in both the short and long-term. This corresponds to an 11% reduction in plaque for the Quigley Hein index (Turesky) in the short term and a 21% reduction in the long term. There was a high degree of heterogeneity that was not explained by the different powered toothbrush type subgroups.There was also moderate quality evidence that powered toothbrushes again provide a statistically significant reduction in gingivitis when compared with manual toothbrushes both in the short and long term. This corresponds to a 6% and 11% reduction in gingivitis for the Löe and Silness indices respectively. Again there was a high degree of heterogeneity that was not explained by the different powered toothbrush type subgroups. The greatest body of evidence was for rotation oscillation brushes which demonstrated a statistically significant reduction in plaque and gingivitis at both time points. Powered toothbrushes reduce plaque and gingivitis more than manual toothbrushing in the short and long term. The clinical importance of these findings remains unclear. Observation of methodological guidelines and greater standardisation of design would benefit both future trials and meta-analyses. Cost, reliability and side effects were inconsistently reported. Any reported side effects were localised and only temporary.

Medical interventions for high grade vulval intraepithelial neoplasia

PubMed Central

Pepas, Litha; Kaushik, Sonali; Bryant, Andrew; Nordin, Andy; Dickinson, Heather O

2014-01-01

Background Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin; its incidence is increasing in women under 50 years. VIN is graded histologically as low grade or high grade. High grade VIN is associated with infection with human papilloma virus (HPV) infection and may progress to invasive disease. There is no consensus on the optimal management of high grade VIN. The high morbidity and high relapse rate associated with surgical interventions call for a formal appraisal of the evidence available for less invasive but effective interventions for high grade VIN. Objectives To evaluate the effectiveness and safety of medical interventions for high grade VIN. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE (up to September 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that assessed medical interventions, in adult women diagnosed with high grade VIN. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis. Main results Four trials met our inclusion criteria: three assessed the effectiveness of topical imiquimod versus placebo in women with high grade VIN; one examined low versus high dose indole-3-carbinol in similar women. Meta-analysis of three trials found that the proportion of women who responded to treatment at 5 to 6 months was much higher in the group who received topical imiquimod than in the group who received placebo (relative risk (RR) = 11.95, 95% confidence interval (CI) 3.21 to 44.51). A single trial showed similar results at 12 months in (RR = 9.10, 95% CI 2.38 to 34.77). Only one trial reported adverse events, which were more common in the imiquimod group. One trial found no significant differences in quality of life (QoL) or body image between the imiquimod and placebo groups. Authors’ conclusions Imiquimod appears to be effective, but its safety needs further examination. Its use is associated with side effects which are tolerable, but more extensive data on adverse effects are required. Long term follow-up should be mandatory in view of the known progression of high grade VIN to invasive disease. Alternative medical interventions, such as cidofovir, should be explored. PMID:21491403

Use of qualitative methods alongside randomised controlled trials of complex healthcare interventions: methodological study

PubMed Central

Glenton, Claire; Oxman, Andrew D

2009-01-01

Objective To examine the use of qualitative approaches alongside randomised trials of complex healthcare interventions. Design Review of randomised controlled trials of interventions to change professional practice or the organisation of care. Data sources Systematic sample of 100 trials published in English from the register of the Cochrane Effective Practice and Organisation of Care Review Group. Methods Published and unpublished qualitative studies linked to the randomised controlled trials were identified through database searches and contact with authors. Data were extracted from each study by two reviewers using a standard form. We extracted data describing the randomised controlled trials and qualitative studies, the quality of these studies, and how, if at all, the qualitative and quantitative findings were combined. A narrative synthesis of the findings was done. Results 30 of the 100 trials had associated qualitative work and 19 of these were published studies. 14 qualitative studies were done before the trial, nine during the trial, and four after the trial. 13 studies reported an explicit theoretical basis and 11 specified their methodological approach. Approaches to sampling and data analysis were poorly described. For most cases (n=20) we found no indication of integration of qualitative and quantitative findings at the level of either analysis or interpretation. The quality of the qualitative studies was highly variable. Conclusions Qualitative studies alongside randomised controlled trials remain uncommon, even where relatively complex interventions are being evaluated. Most of the qualitative studies were carried out before or during the trials with few studies used to explain trial results. The findings of the qualitative studies seemed to be poorly integrated with those of the trials and often had major methodological shortcomings. PMID:19744976

StereoTactic radiotherapy for wet Age-Related macular degeneration (STAR): study protocol for a randomised controlled clinical trial.

PubMed

Neffendorf, James E; Desai, Riti; Wang, Yanzhong; Kelly, Joanna; Murphy, Caroline; Reeves, Barnaby C; Chakravarthy, Usha; Wordsworth, Sarah; Lewis, Cornelius; Peacock, Janet; Uddin, Shahir; O'Sullivan, Joe M; Jackson, Timothy L

2016-11-24

The standard of care for neovascular age-related macular degeneration (nAMD) involves ongoing intravitreal injections of anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF). The most commonly used anti-VEGF drugs are ranibizumab, bevacizumab and aflibercept. The main objective of the STAR trial is to determine if stereotactic radiotherapy can reduce the number of anti-VEGF injections that patients with nAMD require. STAR is a multicentre, double-masked, randomised, sham-controlled clinical trial. It evaluates a new device (manufactured by Oraya, Newark, CA, USA) designed to deliver stereotactic radiotherapy (SRT) to nAMD lesions. The trial enrols participants with chronic, active nAMD. Participants receive a single SRT treatment (16 Gy or sham) with a concomitant baseline intravitreal injection of 0.5 mg ranibizumab. Thereafter, they attend every month for 24 months, and ranibizumab is administered at the visit if retreatment criteria are met. The primary outcome is the number of pro re nata ranibizumab injections during the first 24 months. Secondary outcomes include visual acuity, lesion morphology, quality of life and safety. Additional visits occur at 36 and 48 months to inspect for radiation retinopathy. The target sample size of 411 participants (randomised 2:1 in favour of radiation) is designed to detect a reduction of 2.5 injections against ranibizumab monotherapy, at 90% power, and a significance level (alpha) of 0.025 (one-sided two-sample t test). This gives 97% power to detect non-inferiority of visual acuity at a five-letter margin. The primary analyses will be by intention to treat. The safety and efficacy outcomes will help determine the role of SRT in the management of chronic, active nAMD. International Standard Randomised Controlled Trial Number: ISRCTN12884465. Registered on 28 November 2014. ClinicalTrials.gov: NCT02243878 . Registered on 17 September 2014.

Medical Management of Oral Lichen Planus: A Systematic Review

PubMed Central

Chokshi, Krunal; Desai, Sachin; Malu, Rahul; Chokshi, Achala

2016-01-01

Introduction Oral Lichen Planus (OLP) is a chronic inflammatory, T-cell-mediated autoimmune oral mucosal disease with unclear aetiology. The clinical management of OLP poses considerable difficulties to the oral physician. Aim The aim was to assess the efficacy of any form of intervention used to medically manage OLP. Materials and Methods We searched and analysed the following databases (from January 1990 to December 2014):- Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. All Randomised Controlled Trials (RCTs) for the medical management of OLP which compared active treatment with placebo or between active treatments were considered in this systematic review. Participants of any age, gender or race having symptomatic OLP (including mixed forms), unconnected to any identifiable cause (e.g. lichenoid drug reactions) and confirmed by histopathology have been included. Interventions of all types, including topical treatments or systemic drugs of variable dosage, duration & frequency of delivery have been considered. All the trials identified were appraised by five review authors and the data for all the trials were synthesised using specifically designed data extraction form. Binary data has been presented as risk ratios (RR) with 95% confidence intervals (CI) and continuous data as mean differences (MD) with 95% CIs. Results A total of 35 RCTs were included in this systematic review on medical management of OLP. No strong evidence suggesting superiority of any specific intervention in reducing pain and clinical signs of OLP were shown by the RCTs included here. Conclusion Future RCTs on a larger scale, adopting standardized outcome assessing parameters should be considered. PMID:27042598

Perioperative enhanced recovery programmes for gynaecological cancer patients.

PubMed

Lu, Donghao; Wang, Xuan; Shi, Gang

2012-12-12

Gynaecological malignancies contribute to 10% to 15% of cancers in women internationally. In recent years, a trend towards new perioperative care strategies has been documented as 'Fast Track (FT) surgery', or 'Enhanced Recovery Programmes' to replace some traditional approaches in surgical care. The FT multimodal programmes may enhance the postoperative recovery by means of reducing surgical stress. This systematic review aims to assess fully the beneficial and harmful effects of FT programmes in gynaecological cancer care. To evaluate the beneficial and harmful effects of FT programmes in gynaecological cancer care. We searched the following databases, The Cochrane Gynaecological Cancer Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 4, 2009, MEDLINE and EMBASE to November 2009. In addition, all reference lists of included trials were searched and experts in the gynaecological oncology community were contacted in an attempt to locate trials. This search was updated and re-run to 1 May 2012, for this update. All randomised controlled trials (RCTs) comparing any type of FT programmes for surgery in gynaecological cancer to conventional recovery strategies were included. Two review authors independently screened studies for inclusion. Since no RCTs were identified, data collection and analysis could not be performed. No studies were identified that met the inclusion criteria. We currently have no evidence from high-quality studies to support or refute the use of perioperative enhanced recovery programmes for gynaecological cancer patients. Further well-designed RCTs with standard FT programmes are needed. This review has been updated in 2012. The results of the original review published in 2010 remain unchanged.

Perioperative enhanced recovery programmes for gynaecological cancer patients.

PubMed

Lu, DongHao; Wang, Xuan; Shi, Gang

2015-03-19

Gynaecological malignancies contribute to 10% to 15% of cancers in women internationally. In recent years, a trend towards new perioperative care strategies has been documented as 'Fast Track (FT) surgery', or 'Enhanced Recovery Programmes' to replace some traditional approaches in surgical care. The FT multimodal programmes may enhance the postoperative recovery by means of reducing surgical stress. This systematic review aims to assess fully the beneficial and harmful effects of FT programmes in gynaecological cancer care. To evaluate the beneficial and harmful effects of FT programmes in gynaecological cancer care. We searched the following databases, The Cochrane Gynaecological Cancer Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 4, 2009, MEDLINE and EMBASE to November 2009. In addition, all reference lists of included trials were searched and experts in the gynaecological oncology community were contacted in an attempt to locate trials. This search was updated and re-run in May 2012 and November 2014. All randomised controlled trials (RCTs) comparing any type of FT programmes for surgery in gynaecological cancer to conventional recovery strategies were included. Two review authors independently screened studies for inclusion. Since no RCTs were identified, data collection and analysis could not be performed. No studies were identified that met the inclusion criteria. We currently have no evidence from high-quality studies to support or refute the use of perioperative enhanced recovery programmes for gynaecological cancer patients. Further well-designed RCTs with standard FT programmes are needed. This review has been updated in 2012 and 2014. The results of the original review published in 2010 remain unchanged.

Root-coverage procedures for the treatment of localized recession-type defects: a Cochrane systematic review.

PubMed

Chambrone, Leandro; Sukekava, Flávia; Araújo, Maurício G; Pustiglioni, Francisco E; Chambrone, Luiz Armando; Lima, Luiz A

2010-04-01

The purpose of this review is to evaluate the effectiveness of different root-coverage procedures in the treatment of recession-type defects. The Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE were searched for entries up to October 2008. There were no restrictions regarding publication status or the language of publication. Only clinical randomized controlled trials (RCTs) with a duration > or = 6 months that evaluated recession areas (Miller Class I or II > or = 3 mm) that were treated by means of periodontal plastic surgery procedures were included. Twenty-four RCTs provided data. Only one trial was considered to be at low risk of bias. The remaining trials were considered to be at high risk of bias. The results indicated a significantly greater reduction in gingival recession and gain in keratinized tissue for subepithelial connective tissue grafts (SCTGs) compared to guided tissue regeneration (GTR) with bioabsorbable membranes (GTR bms). A significantly greater gain in keratinized tissue was found for enamel matrix protein compared to a coronally advanced flap (0.40 mm) and for SCTGs compared to GTR bms plus bone substitutes. Limited data exist on the changes of esthetic conditions as related to the opinions and preferences of patients for specific procedures. SCTGs, coronally advanced flaps alone or associated with other biomaterial, and GTR may be used as root-coverage procedures for the treatment of localized recession-type defects. In cases where root coverage and gain in keratinized tissue are expected, the use of SCTGs seems to be more adequate.

Sustained Aeration of Infant Lungs (SAIL) trial: study protocol for a randomized controlled trial.

PubMed

Foglia, Elizabeth E; Owen, Louise S; Thio, Marta; Ratcliffe, Sarah J; Lista, Gianluca; Te Pas, Arjan; Hummler, Helmut; Nadkarni, Vinay; Ades, Anne; Posencheg, Michael; Keszler, Martin; Davis, Peter; Kirpalani, Haresh

2015-03-15

Extremely preterm infants require assistance recruiting the lung to establish a functional residual capacity after birth. Sustained inflation (SI) combined with positive end expiratory pressure (PEEP) may be a superior method of aerating the lung compared with intermittent positive pressure ventilation (IPPV) with PEEP in extremely preterm infants. The Sustained Aeration of Infant Lungs (SAIL) trial was designed to study this question. This multisite prospective randomized controlled unblinded trial will recruit 600 infants of 23 to 26 weeks gestational age who require respiratory support at birth. Infants in both arms will be treated with PEEP 5 to 7 cm H2O throughout the resuscitation. The study intervention consists of performing an initial SI (20 cm H20 for 15 seconds) followed by a second SI (25 cm H2O for 15 seconds), and then PEEP with or without IPPV, as needed. The control group will be treated with initial IPPV with PEEP. The primary outcome is the combined endpoint of bronchopulmonary dysplasia or death at 36 weeks post-menstrual age. www.clinicaltrials.gov , Trial identifier NCT02139800 , Registered 13 May 2014.

The effects of amino acid infusions on core body temperature during the perioperative period: a systematic review.

PubMed

Zhou, Bo; Wang, Gang; Yang, Shuofei; He, Xiandi; Liu, Yun

2014-12-01

The aim of this systematic review was to determine the effect of amino acid infusions on core body temperature and shivering. We searched the PubMed, EMBASE, CINAHL, and Cochrane Register of Controlled Trials databases to identify randomized controlled trials that met the inclusion criteria. A total of 11 eligible trials involving 506 participants were identified. Amino acid infusions were associated with shorter periods of mechanical ventilation and hospitalization and less perioperative shivering, mechanical intubation, and hospitalization in surgical patients without hepatic, renal, or severe metabolic disorders. It is recommended that infusions are warmed before administration to avoid further decrease in core body temperature. Copyright © 2014 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Ergonomic positioning or equipment for treating carpal tunnel syndrome.

PubMed

O'Connor, Denise; Page, Matthew J; Marshall, Shawn C; Massy-Westropp, Nicola

2012-01-18

Non-surgical treatment, including ergonomic positioning or equipment, are sometimes offered to people experiencing mild to moderate symptoms from carpal tunnel syndrome (CTS). The effectiveness and duration of benefit from ergonomic positioning or equipment interventions for treating CTS are unknown. To assess the effects of ergonomic positioning or equipment compared with no treatment, a placebo or another non-surgical intervention in people with CTS. We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 June 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 2, in The Cochrane Library), MEDLINE (1966 to June 2011), EMBASE (1980 to June 2011), CINAHL Plus (1937 to June 2011), and AMED (1985 to June 2011). We also reviewed the reference lists of randomised or quasi-randomised trials identified from the electronic search. Randomised or quasi-randomised controlled trials comparing ergonomic positioning or equipment with no treatment, placebo or another non-surgical intervention in people with CTS. Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias of included studies. We calculated risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for the primary and secondary outcomes. We pooled results of clinically and statistically homogeneous trials, where possible, to provide estimates of the effect of ergonomic positioning or equipment. We included two trials (105 participants) comparing ergonomic versus placebo keyboards. Neither trial assessed the primary outcome (short-term overall improvement) or adverse effects of interventions. In one small trial (25 participants) an ergonomic keyboard significantly reduced pain after 12 weeks (MD -2.40; 95% CI -4.45 to -0.35) but not six weeks (MD -0.20; 95% CI -1.51 to 1.11). In this same study, there was no difference between ergonomic and standard keyboards in hand function at six or 12 weeks or palm-wrist sensory latency at 12 weeks. The second trial (80 participants) reported no significant difference in pain severity after six months when using either of the three ergonomic keyboards versus a standard keyboard. No trials comparing (i) ergonomic positioning or equipment with no treatment, (ii) ergonomic positioning or equipment with another non-surgical treatment, or (iii) different ergonomic positioning or equipment regimes, were found. There is insufficient evidence from randomised controlled trials to determine whether ergonomic positioning or equipment is beneficial or harmful for treating carpal tunnel syndrome.

Tongue scraping for treating halitosis.

PubMed

Outhouse, T L; Al-Alawi, R; Fedorowicz, Z; Keenan, J V

2006-04-19

Halitosis is used to describe any disagreeable odour of expired air regardless of its origin. Mouthwashes which disguise oral malodor are more socially acceptable and generally more popular than tongue scrapers. To provide reliable evidence regarding the effectiveness of tongue scraping versus other interventions (including mouthwashes) to control halitosis. We searched the following databases: Cochrane Oral Health Group Trials Register (to 15th September 2005); the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3 2005); MEDLINE 1966 to September Week 1 2005; EMBASE 1974 to September 2005 (searched September 19th 2005). Randomized controlled trials comparing different methods of tongue cleaning to reduce mouth odour in adults with halitosis. Clinical heterogeneity between the two included trials precluded pooling of data, therefore a descriptive summary is presented. This review included two trials involving 40 participants. Both trials were methodologically sound but included no data for the primary outcomes specified in this review. Secondary outcomes expressed as volatile sulfur compound (VSC) levels were assessed by a portable sulfide monitor in both trials. One trial showed reductions of VSC levels of 42% with the tongue cleaner, 40% with the tongue scraper and 33% with the toothbrush. Reduced VSC levels persisted longer with the tongue cleaner than the toothbrush and could not be detected for more than 30 minutes after the intervention in any of the groups. Differences were assessed by the Friedman and Wilcoxon signed rank tests with the level of significance set at P < 0.05. The second trial, in which differences in totaled rank values between groups were compared by the Dunn method alpha = 0.01, showed a reduction of VSC levels compared with baseline measurements of 75% with the tongue scraper and 45% with the toothbrush. Adverse effects in one trial were nausea (60%) and trauma (10%) with the toothbrush and all participants receptive to using the tongue scraper. Based on the independent data from these two trials there was a statistically significant difference between the effectiveness of either the tongue cleaner or the tongue scraper in reducing VSC levels when compared with the toothbrush. There is weak and unreliable evidence to show that there is a small but statistically significant difference in reduction of VSC levels when tongue scrapers or cleaners rather than toothbrushes are used to reduce halitosis in adults. We found no high level evidence comparing mechanical with other forms of tongue cleaning.

Laser therapy may be better than topical desensitizing agents for treating dentin hypersensitivity.

PubMed

Blatz, Markus B

2012-09-01

Two independent reviewers screened the databases MEDLINE, EMBASE, the Cochrane Central Register of ControlledTrials, the National Research Register, and the Cochrane Oral HealthGroup'sTrials Register for articles written in English between 1977 and January1, 2010. The inclusion criteria comprised randomized controlled trials (RCTs) involving the application of laser desensitizing procedures and topical desensitizing agents in patients with at least 2 or more hypersensitive teeth confirmed by evaporative stimulus or tactile hypersensitivity assessment. Trial groups needed to receive laser therapy, whereas the control groups received topical desensitizing agents, such as fluoride varnish, dentin bonding agents, or others. Outcomes had to be measured by clinical performance (decrease of hypersensitivity) and/or patients' self-assessment. Studies with loss in follow-up greater than 20% or with confusing data/probable errors were excluded. A total of 176 potential relevant titles, abstracts, and articles were found, 28 of which were screened for further evaluation. Out of these, 8 trials met all inclusion criteria, involving a total of 234 patients. The quality of these trials was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. Accordingly, only 1 study was classified as A level, 5 as B level, and 2 as C level. A meta-analysis was not performed because of the heterogeneity of the studies. Studies that assess the application of laser desensitizing procedures in reducing dentinal hypersensitivity. The primary outcome was reduction of tooth sensitivity following treatment with either a laser or a topical desensitizing agent. Evaluations were made at varying intervals up to 6 months after treatment. Eight trials reporting on a total of 234 patients were included based on the specified criteria and 20 articles were excluded. Sample size in each of the included studies varied from 20 to 70 patients with differing follow-up intervals of up to 6 months. Most studies used Visual Analog Scale scores or other subjective tools to assess sensitivity. All 8 studies compared one kind of laser versus one kind of topical desensitizingagent. However, types of lasers as well as types of desensitizing agents differed among the reviewed studies. Half of the studies compared gallium-aluminum-arsenide (GaAlAs) lasers with various topical desensitizing agents; however, findings were conflicting. Two moderate-quality trials indicated that GaAlAs laser and the control desensitizing agents preformed similarly. Another moderate-quality trial demonstrated that the application of a bonding agent was significantly better than a GaAlAs laser in the reduction of hypersensitivity. The only reviewed study that was classified as an A-level study revealed a significantly greater immediate and long-term desensitizing effect than the control. The remaining studies involved Nd:YAG, Er:YAG, and CO(2) lasers, all of them reporting a slightly greater decrease in sensitivity as compared with topical desensitizing agents. Five of 8s tudies reported on the safety of laser application and did not find any detrimental pulpal effects, allergic reactions, or clinically detectable complications during follow-up. The authors concluded that the results obtained from the 8 studies included in this systematic review were conflicting but indicated a slight clinical advantage of laser therapy over topical medicaments in the treatment of dentin hypersensitivity. It was further concluded that application of lasers under controlled parameters for this indication may not lead to adverse effects. Copyright © 2012. Published by Mosby, Inc. All rights reserved.

Femoral nerve block Intervention in Neck of Femur fracture (FINOF): study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Hip fractures are very painful leading to lengthy hospital stays. Conventional methods of treating pain are limited. Non-steroidal anti-inflammatories are relatively contraindicated and opioids have significant side effects.Regional anaesthesia holds promise but results from these techniques are inconsistent. Trials to date have been inconclusive with regard to which blocks to use and for how long. Interpatient variability remains a problem. Methods/Design This is a single centre study conducted at Queen’s Medical Centre, Nottingham; a large regional trauma centre in England. It is a pragmatic, parallel arm, randomized controlled trial. Sample size will be 150 participants (75 in each group). Randomization will be web-based, using computer generated concealed tables (service provided by Nottingham University Clinical Trials Unit). There is no blinding. Intervention will be a femoral nerve block (0.5 mls/kg 0.25% levo-bupivacaine) followed by ropivacaine (0.2% 5 ml/hr−1) infused via a femoral nerve catheter until 48 hours post-surgery. The control group will receive standard care. Participants will be aged over 70 years, cognitively intact (abbreviated mental score of seven or more), able to provide informed consent, and admitted directly through the Emergency Department from their place of residence. Primary outcomes will be cumulative ambulation score (from day 1 to 3 postoperatively) and cumulative dynamic pain scores (day 1 to 3 postoperatively). Secondary outcomes will be cumulative dynamic pain score preoperatively, cumulative side effects, cumulative calorific and protein intake, EUROQOL EQ-5D score, length of stay, and rehabilitation outcome (measured by mobility score). Discussion Many studies have shown the effectiveness of regional blockade in neck of femur fractures, but the techniques used have varied. This study aims to identify whether early and continuous femoral nerve block can be effective in relieving pain and enhancing mobilization.Trial registration. Trial registration The trial is registered with the European clinical trials database Eudract ref: 2010-023871-25. (17/02/2011). ISRCTN: ISRCTN92946117. Registered 26 October 2012. PMID:24885267

Effect of joint mobilization techniques for primary total knee arthroplasty: Study protocol for a randomized controlled trial.

PubMed

Xu, Jiao; Zhang, Juan; Wang, Xue-Qiang; Wang, Xuan-Lin; Wu, Ya; Chen, Chan-Cheng; Zhang, Han-Yu; Zhang, Zhi-Wan; Fan, Kai-Yi; Zhu, Qiang; Deng, Zhi-Wei

2017-12-01

Total knee arthroplasty (TKA) has become the most preferred procedure by patients for the relief of pain caused by knee osteoarthritis. TKA patients aim a speedy recovery after the surgery. Joint mobilization techniques for rehabilitation have been widely used to relieve pain and improve joint mobility. However, relevant randomized controlled trials showing the curative effect of these techniques remain lacking to date. Accordingly, this study aims to investigate whether joint mobilization techniques are valid for primary TKA. We will manage a single-blind, prospective, randomized, controlled trial of 120 patients with unilateral TKA. Patients will be randomized into an intervention group, a physical modality therapy group, and a usual care group. The intervention group will undergo joint mobilization manipulation treatment once a day and regular training twice a day for a month. The physical modality therapy group will undergo physical therapy once a day and regular training twice a day for a month. The usual care group will perform regular training twice a day for a month. Primary outcome measures will be based on the visual analog scale, the knee joint Hospital for Special Surgery score, range of motion, surrounded degree, and adverse effect. Secondary indicators will include manual muscle testing, 36-Item Short Form Health Survey, Berg Balance Scale function evaluation, Pittsburgh Sleep Quality Index, proprioception, and muscle morphology. We will direct intention-to-treat analysis if a subject withdraws from the trial. The important features of this trial for joint mobilization techniques in primary TKA are randomization procedures, single-blind, large sample size, and standardized protocol. This study aims to investigate whether joint mobilization techniques are effective for early TKA patients. The result of this study may serve as a guide for TKA patients, medical personnel, and healthcare decision makers. It has been registered at http://www.chictr.org.cn/showproj.aspx?proj=15262 (Identifier:ChiCTR-IOR-16009192), Registered 11 September 2016. We also could provide the correct URL of the online registry in the WHO Trial Registration. http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR-IOR-16009192.

Recruiting to a large-scale physical activity randomised controlled trial - experiences with the gift of hindsight.

PubMed

Copeland, Robert J; Horspool, Kimberley; Humphreys, Liam; Scott, Emma

2016-02-24

Recruitment issues continue to impact a large number of trials. Sharing recruitment information is vital to supporting researchers to accurately predict recruitment and to manage the risk of poor recruitment during study design and implementation. The purpose of this article is to build on the knowledge available to researchers on recruiting to community-based trials. A critical commentary of the recruitment challenges encountered during the Booster Study, a randomised controlled trial in which researchers investigated the effectiveness of a motivational interviewing style intervention on the maintenance of physical activity. An overview of recruitment is provided, as well as strategies employed to recruit prospective participants and possible barriers to recruitment. Two hundred eighty-two people, 47 % of the original target, were recruited through mail-outs, with secondary recruitment pathways yielding no additional participants. The research team encountered problems with recontacting interested participants and providing study materials in non-English languages. A lower response rate to the mail-out and a greater number of non-contactable participants in the full study than in the pilot study resulted in a smaller pool of eligible participants from the brief intervention eligible for recruitment into the randomised controlled trial. Despite using widely accepted recruitment strategies and incorporating new recruitment tactics in response to challenges, the Booster Study investigators failed to randomise a sufficient number of participants. Recruitment in trials of community-based behavioural interventions may have different challenges than trials based on clinical or primary care pathways. Specific challenges posed by the complexity of the study design and problems with staffing and resources were exacerbated by the need to revise upwards the number of mailed invitations as a result of the pilot study. Researchers should ensure study design facilitates recruitment and consider the implications of changing recruitment on the operational aspects of the trial. Where possible, the impact of new strategies should be measured, and recruitment successes and challenges should be shared with those planning similar studies. ISRCTN56495859 (registered on 12 February 2009); NCT00836459 (registered on 3 February 2009).

Acute cholecystitis in high risk surgical patients: percutaneous cholecystostomy versus laparoscopic cholecystectomy (CHOCOLATE trial): Study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Laparoscopic cholecystectomy in acute calculous cholecystitis in high risk patients can lead to significant morbidity and mortality. Percutaneous cholecystostomy may be an alternative treatment option but the current literature does not provide the surgical community with evidence based advice. Methods/Design The CHOCOLATE trial is a randomised controlled, parallel-group, superiority multicenter trial. High risk patients, defined as APACHE-II score 7-14, with acute calculous cholecystitis will be randomised to laparoscopic cholecystectomy or percutaneous cholecystostomy. During a two year period 284 patients will be enrolled from 30 high volume teaching hospitals. The primary endpoint is a composite endpoint of major complications within three months following randomization and need for re-intervention and mortality during the follow-up period of one year. Secondary endpoints include all other complications, duration of hospital admission, difficulty of procedures and total costs. Discussion The CHOCOLATE trial is designed to provide the surgical community with an evidence based guideline in the treatment of acute calculous cholecystitis in high risk patients. Trial Registration Netherlands Trial Register (NTR): NTR2666 PMID:22236534

Email for communicating results of diagnostic medical investigations to patients.

PubMed

Meyer, Barbara; Atherton, Helen; Sawmynaden, Prescilla; Car, Josip

2012-08-15

As medical care becomes more complex and the ability to test for conditions grows, pressure on healthcare providers to convey increasing volumes of test results to patients is driving investigation of alternative technological solutions for their delivery. This review addresses the use of email for communicating results of diagnostic medical investigations to patients. To assess the effects of using email for communicating results of diagnostic medical investigations to patients, compared to SMS/ text messaging, telephone communication or usual care, on outcomes, including harms, for health professionals, patients and caregivers, and health services. We searched: the Cochrane Consumers and Communication Review Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1 2010), MEDLINE (OvidSP) (1950 to January 2010), EMBASE (OvidSP) (1980 to January 2010), PsycINFO (OvidSP) (1967 to January 2010), CINAHL (EbscoHOST) (1982 to February 2010), and ERIC (CSA) (1965 to January 2010). We searched grey literature: theses/dissertation repositories, trials registers and Google Scholar (searched July 2010). We used additional search methods: examining reference lists and contacting authors. Randomised controlled trials, quasi-randomised trials, controlled before and after studies and interrupted time series studies of interventions using email for communicating results of any diagnostic medical investigations to patients, and taking the form of 1) unsecured email 2) secure email or 3) web messaging. All healthcare professionals, patients and caregivers in all settings were considered. Two review authors independently assessed the titles and abstracts of retrieved citations. No studies were identified for inclusion. Consequently, no data collection or analysis was possible. No studies met the inclusion criteria, therefore there are no results to report on the use of email for communicating results of diagnostic medical investigations to patients. In the absence of included studies, we can draw no conclusions on the effects of using email for communicating results of diagnostic medical investigations to patients, and thus no recommendations for practice can be stipulated. Further well-designed research should be conducted to inform practice and policy for communicating patient results via email, as this is a developing area.

[Clinical trials registry].

PubMed

Ryder, Elena

2004-12-01

Authors and journals are more enthusiastic about the publication of trials with positive results than those negative or inconclusive trials. The International Committee of Medical Journal Editors proposed comprehensive trials registration as a solution to the problem of selective awareness and announces that the ICMJE member journals will adopt a trial-registration policy to promote this goal. They establish as a condition of consideration for publication, registration in a public trials registry. They recommend registries that meet certain criteria as www.clinicaltrials.com. Among those criteria is that the registry must be supported by a non-profit organization. On the other hand, people from Current Controlled Trials Ltd. being a commercial company, but meeting all the other criteria established by the ICMJE, feel that is being put aside. We wonder if clinical trials in our country are being registered in some of these International Registries. If not, would it be time to do so?

Proactive palliative care for patients with COPD (PROLONG): a pragmatic cluster controlled trial

PubMed Central

Duenk, RG; Verhagen, C; Bronkhorst, EM; van Mierlo, PJWB; Broeders, MEAC; Collard, SM; Dekhuijzen, PNR; Vissers, KCP

2017-01-01

Background and aim Patients with advanced chronic obstructive pulmonary disease (COPD) have poor quality of life. The aim of this study was to assess the effects of proactive palliative care on the well-being of these patients. Trial registration This trial is registered with the Netherlands Trial Register, NTR4037. Patients and methods A pragmatic cluster controlled trial (quasi-experimental design) was performed with hospitals as cluster (three intervention and three control) and a pretrial assessment was performed. Hospitals were selected for the intervention group based on the presence of a specialized palliative care team (SPCT). To control for confounders, a pretrial assessment was performed in which hospitals were compared on baseline characteristics. Patients with COPD with poor prognosis were recruited during hospitalization for acute exacerbation. All patients received usual care while patients in the intervention group received additional proactive palliative care in monthly meetings with an SPCT. Our primary outcome was change in quality of life score after 3 months, which was measured using the St George Respiratory Questionnaire (SGRQ). Secondary outcomes were, among others, quality of life at 6, 9 and 12 months; readmissions: survival; and having made advance care planning (ACP) choices. All analyses were performed following the principle of intention to treat. Results During the year 2014, 228 patients (90 intervention and 138 control) were recruited and at 3 months, 163 patients (67 intervention and 96 control) completed the SGRQ. There was no significant difference in change scores of the SGRQ total at 3 months between groups (−0.79 [95% CI, −4.61 to 3.34], p=0.70). However, patients who received proactive palliative care experienced less impact of their COPD (SGRQ impact subscale) at 6 months (−6.22 [−11.73 to −0.71], p=0.04) and had more often made ACP choices (adjusted odds ratio 3.26 [1.49–7.14], p=0.003). Other secondary outcomes were not significantly different. Conclusion Proactive palliative care did not improve the overall quality of life of patients with COPD. However, patients more often made ACP choices which may lead to better quality of care toward the end of life. PMID:29033560

Effectiveness of proactive telephone counselling for smoking cessation in parents: Study protocol of a randomized controlled trial

PubMed Central

2011-01-01

Background Smoking is the world's fourth most common risk factor for disease, the leading preventable cause of death, and it is associated with tremendous social costs. In the Netherlands, the smoking prevalence rate is high. A total of 27.7% of the population over age 15 years smokes. In addition to the direct advantages of smoking cessation for the smoker, parents who quit smoking may also decrease their children's risk of smoking initiation. Methods/Design A randomized controlled trial will be conducted to evaluate the effectiveness of proactive telephone counselling to increase smoking cessation rates among smoking parents. A total of 512 smoking parents will be proactively recruited through their children's primary schools and randomly assigned to either proactive telephone counselling or a control condition. Proactive telephone counselling will consist of up to seven counsellor-initiated telephone calls (based on cognitive-behavioural skill building and Motivational Interviewing), distributed over a period of three months. Three supplementary brochures will also be provided. In the control condition, parents will receive a standard brochure to aid smoking cessation. Assessments will take place at baseline, three months after start of the intervention (post-measurement), and twelve months after start of the intervention (follow-up measurement). Primary outcome measures will include sustained abstinence between post-measurement and follow-up measurement and 7-day point prevalence abstinence and 24-hours point prevalence abstinence at both post- and follow-up measurement. Several secondary outcome measures will also be included (e.g., smoking intensity, smoking policies at home). In addition, we will evaluate smoking-related cognitions (e.g., attitudes towards smoking, social norms, self-efficacy, intention to smoke) in 9-12 year old children of smoking parents. Discussion This study protocol describes the design of a randomized controlled trial to evaluate the effectiveness of proactive telephone counselling in smoking cessation. It is expected that, in the telephone counseling condition, parental smoking cessation rates will be higher and children's cognitions will be less favorable about smoking compared to the control condition. Trial registration The protocol for this study is registered with the Netherlands Trial Register NTR2707. PMID:21943207

The influence of a long-term growth hormone treatment on lipid and glucose metabolism: a randomized trial in short Japanese children born small for gestational age.

PubMed

Horikawa, Reiko; Tanaka, Toshiaki; Nishinaga, Hiromi; Ogawa, Yoshihisa; Yokoya, Susumu

2016-01-01

Long-term growth hormone (GH) treatments in short children born small for gestational age (SGA) restore lipid metabolism, but also increase insulin resistance. The aim of this study was to evaluate the influence of long-term GH therapy on lipid and glucose metabolism as well as its dose dependency in short Japanese children born SGA. Eighty Japanese children with a short stature who were born SGA participated in this study; 65 were treated with fixed GH doses of 0.033 (low) or 0.067 (high) mg/kg/day for 260 weeks; 15 were untreated controls in the first year and were randomized to one of the two treatment groups at week 52. Serum cholesterol, glucose and insulin levels were regularly measured. An oral glucose tolerance test (OGTT) was conducted annually. The mean age at the start of GH therapy was approximately 5.3 years. Serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the high dose group significantly decreased over time during GH therapy. In both dose groups for TC, and in the high dose group for LDL-C, the higher the baseline values, the greater the decrease after 260 weeks. The rate of the decrease observed after 260 weeks in patients with high LDL-C levels was greater in the high dose group. Based on the results of OGTT, no patient was classified as being diabetic; however, annual increases were observed in post-OGTT insulin levels. After 260 weeks, the homeostasis model assessment as an index of insulin resistance (HOMA-IR) increased, suggesting that insulin resistance developed over time with the GH treatment, while 36.6 % of the subjects entered puberty. Long-term continuous GH treatment for children born SGA may have a potentially beneficial effect on several parameters in lipid metabolism and does not adversely affect glucose metabolism. GHLIQUID-1516, GHLIQUID-1517, Japan Pharmaceutical Information Center Clinical trial registration: JapicCTI-050132. Registered 13 September 2005. Retrospectively registered. JapicCTI-050137. Registered 13 September 2005. Retrospectively registered. ClinicalTrials.gov trial registration: NCT00184717. Registered 13 September 2005. Retrospectively registered.

Topical application of tranexamic acid for the reduction of bleeding.

PubMed

Ker, Katharine; Beecher, Deirdre; Roberts, Ian

2013-07-23

Intravenous tranexamic acid reduces bleeding in surgery, however, its effect on the risk of thromboembolic events is uncertain and an increased risk remains a theoretical concern. Because there is less systemic absorption following topical administration, the direct application of tranexamic acid to the bleeding surface has the potential to reduce bleeding with minimal systemic effects. To assess the effects of the topical administration of tranexamic acid in the control of bleeding. We searched the Cochrane Injuries Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library; Ovid MEDLINE®, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Ovid MEDLINE® Daily and Ovid OLDMEDLINE®; Embase Classic + Embase (OvidSP); PubMed and ISI Web of Science (including Science Citation Index Expanded and Social Science Citation Index (SCI-EXPANDED & CPCI-S)). We also searched online trials registers to identify ongoing or unpublished trials. The search was run on the 31st May 2013. Randomised controlled trials comparing topical tranexamic acid with no topical tranexamic acid or placebo in bleeding patients. Two authors examined the titles and abstracts of citations from the electronic databases for eligibility. Two authors extracted the data and assessed the risk of bias for each trial. Outcome measures of interest were blood loss, mortality, thromboembolic events (myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism) and receipt of a blood transfusion. We included 29 trials involving 2612 participants. Twenty-eight trials involved patients undergoing surgery and one trial involved patients with epistaxis (nosebleed). Tranexamic acid (TXA) reduced blood loss by 29% (pooled ratio 0.71, 95% confidence interval (CI) 0.69 to 0.72; P < 0.0001). There was uncertainty regarding the effect on death (risk ratio (RR) 0.28, 95% CI 0.06 to 1.34; P = 0.11), myocardial infarction (RR 0.33, 95% CI 0.04 to 3.08; P = 0.33), stroke (RR 0.33, 95% CI 0.01 to 7.96; P = 0.49), deep vein thrombosis (RR 0.69, 95% CI 0.31 to 1.57; P = 0.38) and pulmonary embolism (RR 0.52, 95% CI 0.09 to 3.15; P = 0.48). TXA reduced the risk of receiving a blood transfusion by a relative 45% (RR 0.55, 95% CI 0.55 to 0.46; P < 0.0001). There was substantial statistical heterogeneity between trials for the blood loss and blood transfusion outcomes. There is reliable evidence that topical application of tranexamic acid reduces bleeding and blood transfusion in surgical patients, however the effect on the risk of thromboembolic events is uncertain. The effects of topical tranexamic acid in patients with bleeding from non-surgical causes has yet to be reliably assessed. Further high-quality trials are warranted to resolve these uncertainties before topical tranexamic acid can be recommended for routine use.

Corticosteroids as adjuvant therapy for ocular toxoplasmosis.

PubMed

Jasper, Smitha; Vedula, Satyanarayana S; John, Sheeja S; Horo, Saban; Sepah, Yasir J; Nguyen, Quan Dong

2013-04-30

Ocular infestation with Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea and consequently lead to complications such as glaucoma, cataract, and posterior synechiae. The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids for ocular toxoplasmosis. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to October 2012), EMBASE (January 1980 to October 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We searched the reference lists of included studies for any additional studies not identified by the electronic searches. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 October 2012. We planned to include randomized and quasi-randomized controlled trials. Eligible trials would have enrolled participants of any age who were immunocompetent and were diagnosed with active ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, or different doses or times of initiation of corticosteroids. Two authors independently screened titles and abstracts retrieved from the electronic searches. We retrieved full-text articles of studies categorized as 'unsure' or 'include' after review of the abstracts. Two authors independently reviewed each full-text article. Discrepancies were resolved through discussion. The electronic searches retrieved 368 titles and abstracts. We reviewed 20 full-text articles. We identified no trials eligible for inclusion in this systematic review. Although research has identified wide variation in practices regarding use of corticosteroids, our systematic review did not identify evidence from randomized controlled trials for the role of corticosteroids in the management of ocular toxoplasmosis. Several questions remain unanswered by well-conducted randomized trials in this context, including whether use of corticosteroids is more effective than use of anti-parasitic therapy alone, when corticosteroids should be initiated in the treatment regimen (early versus late course of treatment), and which dosage and duration of steroid use is best. These questions are easily amenable to research using a randomized controlled design and they are ethical due to the absence of evidence to support or discourage use of corticosteroids for this condition. The question of foremost importance, however, is whether they should be used as adjunct therapy (that is, additional) to anti-parasitic agents.

Corticosteroids for ocular toxoplasmosis

PubMed Central

Jasper, Smitha; Vedula, Satyanarayana S; John, Sheeja S; Horo, Saban; Sepah, Yasir J; Nguyen, Quan Dong

2014-01-01

Background Ocular infestation with Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea and consequently lead to complications such as glaucoma, cataract, and posterior synechiae. Objectives The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids for ocular toxoplasmosis. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to October 2012), EMBASE (January 1980 to October 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We searched the reference lists of included studies for any additional studies not identified by the electronic searches. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 October 2012. Selection criteria We planned to include randomized and quasi-randomized controlled trials. Eligible trials would have enrolled participants of any age who were immunocompetent and were diagnosed with active ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, or different doses or times of initiation of corticosteroids. Data collection and analysis Two authors independently screened titles and abstracts retrieved from the electronic searches. We retrieved full-text articles of studies categorized as ‘unsure’ or ‘include’ after review of the abstracts. Two authors independently reviewed each full-text article. Discrepancies were resolved through discussion. Main results The electronic searches retrieved 368 titles and abstracts. We reviewed 20 full-text articles. We identified no trials eligible for inclusion in this systematic review. Authors' conclusions Although research has identified wide variation in practices regarding use of corticosteroids, our systematic review did not identify evidence from randomized controlled trials for the role of corticosteroids in the management of ocular toxoplasmosis. Several questions remain unanswered by well-conducted randomized trials in this context, including whether use of corticosteroids is more effective than use of anti-parasitic therapy alone, when corticosteroids should be initiated in the treatment regimen (early versus late course of treatment), and which dosage and duration of steroid use is best. These questions are easily amenable to research using a randomized controlled design and they are ethical due to the absence of evidence to support or discourage use of corticosteroids for this condition. The question of foremost importance, however, is whether they should be used as adjunct therapy (that is, additional) to anti-parasitic agents. PMID:23633342

Publication proportions for registered breast cancer trials: before and following the introduction of the ClinicalTrials.gov results database.

PubMed

Asiimwe, Innocent Gerald; Rumona, Dickson

2016-01-01

To limit selective and incomplete publication of the results of clinical trials, registries including ClinicalTrials.gov were introduced. The ClinicalTrials.gov registry added a results database in 2008 to enable researchers to post the results of their trials as stipulated by the Food and Drug Administration Amendment Act of 2007. This study aimed to determine the direction and magnitude of any change in publication proportions of registered breast cancer trials that occurred since the inception of the ClinicalTrials.gov results database. A cross-sectional study design was employed using ClinicalTrials.gov, a publicly available registry/results database as the primary data source. Registry contents under the subcategories 'Breast Neoplasms' and 'Breast Neoplasms, Male' were downloaded on 1 August 2015. A literature search for included trials was afterwards conducted using MEDLINE and DISCOVER databases to determine publication status of the registered breast cancer trials. Nearly half (168/340) of the listed trials had been published, with a median time to publication of 24 months (Q1 = 14 months, Q3 = 42 months). Only 86 trials were published within 24 months of completion. There was no significant increase in publication proportions of trials that were completed before the introduction of the results database compared to those completed after (OR = 1.00, 95 % CI = .61 to 1.63; adjusted OR = 0.84, 95 % CI = .51 to 1.39). Characteristics associated with publication included trial type (observational versus interventional adjusted OR = .28, 95 % CI = .10 to .74) and completion/termination status (terminated versus completed adjusted OR = .22, 95 % CI = .09 to .51). Less than a half of breast cancer trials registered in ClinicalTrials.gov are published in peer-reviewed journals.

Herbal medicine for low back pain: a Cochrane review.

PubMed

Gagnier, Joel J; van Tulder, Maurits W; Berman, Brian; Bombardier, Claire

2007-01-01

A systematic review of randomized controlled trials. To determine the effectiveness of herbal medicine compared with placebo, no intervention, or "standard/accepted/conventional treatments" for nonspecific low back pain. Low back pain is a common condition and a substantial economic burden in industrialized societies. A large proportion of patients with chronic low back pain use complementary and alternative medicine (CAM) and/or visit CAM practitioners. Several herbal medicines have been purported for use in low back pain. The following databases were searched: Medline (1966 to April 2003), Embase (1980 to April 2003), Cochrane Controlled Trials Register (Issue 1, 2003), and Cochrane Complementary Medicine (CM) field Trials Register. Additionally, reference lists in review articles, guidelines, and in the retrieved trials were checked. Randomized controlled trials (RCTs), using adults (>18 years of age) suffering from acute, subacute, or chronic nonspecific low back pain. Types of interventions included herbal medicines defined as a plant that is used for medicinal purposes in any form. Primary outcome measures were pain and function. Two reviewers (J.J.G. and M.W.T.) conducted electronic searches in all databases. One reviewer (J.J.G.) contacted content experts and acquired relevant citations. Authors, title, subject headings, publication type, and abstract of the isolated studies were downloaded or a hard copy was retrieved. Methodologic quality and clinical relevance were assessed separately by two individuals (J.J.G. and M.W.T.). Disagreements were resolved by consensus. Ten trials were included in this review. Two high-quality trials utilizing Harpagophytum procumbens (Devil's claw) found strong evidence for short-term improvements in pain and rescue medication for daily doses standardized to 50 mg or 100 mg harpagoside with another high-quality trial demonstrating relative equivalence to 12.5 mg per day of rofecoxib. Two moderate-quality trials utilizing Salix alba (White willow bark) found moderate evidence for short-term improvements in pain and rescue medication for daily doses standardized to 120 mg or 240 mg salicin with an additional trial demonstrating relative equivalence to 12.5 mg per day of rofecoxib. Three low-quality trials using Capsicum frutescens (Cayenne) using various topical preparations found moderate evidence for favorable results against placebo and one trial found equivalence to a homeopathic ointment. Harpagophytum procumbens, Salix alba, and Capsicum frutescens seem to reduce pain more than placebo. Additional trials testing these herbal medicines against standard treatments will clarify their equivalence in terms of efficacy. The quality of reporting in these trials was generally poor; thus, trialists should refer to the CONSORT statement in reporting clinical trials of herbal medicines.

Relation between burden of disease and randomised evidence in sub-Saharan Africa: survey of research.

PubMed

Isaakidis, Petros; Swingler, George H; Pienaar, Elizabeth; Volmink, Jimmy; Ioannidis, John P A

2002-03-23

To evaluate whether the amount of randomised clinical research on various medical conditions is related to the burden of disease and health needs of the local populations in sub-Saharan Africa. Construction and analysis of comprehensive database of randomised controlled trials in sub-Saharan Africa based on Medline, the Cochrane Controlled Trials Register, and several African databases. Sub-Saharan Africa. Number of trials and randomised subjects for each category of disease in the global burden of disease taxonomy; ratios of disability adjusted life years (DALYs) per amount of randomised evidence. 1179 eligible randomised controlled trials were identified. The number of trials published each year increased over time. Almost half of the trials (n=565) had been done in South Africa. There was relatively good correlation between the estimated burden of disease at year 2000 and the number of trials performed (r=0.53, P=0.024) and the number of participants randomised (r=0.68, P=0.002). However,some conditions-for example, injuries (over 20 000 DALYs per patient ever randomised)-were more neglected than others. Despite recent improvements, few clinical trials are done in sub-Saharan Africa. Clinical research in this part of the world should focus more evenly on the major contributors to burden of disease.

Email for the coordination of healthcare appointments and attendance reminders.

PubMed

Atherton, Helen; Sawmynaden, Prescilla; Meyer, Barbara; Car, Josip

2012-08-15

Email is a popular and commonly-used method of communication, but its use in health care is not routine. Where email communication has been utilised in health care, its purposes have included the coordination of healthcare appointments and attendance reminders, but the effects of using email in this way are not known. This review considers the use of email for the coordination of healthcare appointments and reminders for attendance; particularly scheduling, rescheduling and cancelling healthcare appointments, and providing prompts/reminders for attendance at appointments. To assess the effects of using email for the coordination of healthcare appointments and attendance reminders, compared to other forms of coordinating appointments and reminders, on outcomes for health professionals, patients and carers, and health services, including harms. We searched: the Cochrane Consumers and Communication Review Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1 2010), MEDLINE (OvidSP) (1950 to January 2010), EMBASE (OvidSP) (1980 to January 2010), PsycINFO (OvidSP) (1967 to January 2010), CINAHL (EbscoHOST) (1982 to February 2010),and ERIC (CSA) (1965 to January 2010). We searched grey literature: theses/dissertation repositories, trials registers and Google Scholar (searched July 2010). We used additional search methods: examining reference lists and contacting authors. Randomised controlled trials, quasi-randomised trials, controlled before and after studies and interrupted time series studies of interventions that use email for scheduling health appointments, for reminders for a scheduled health appointment or for ongoing coordination of health appointments and that took the form of 1) unsecured email 2) secure email or 3) web messaging. All healthcare professionals, patients and caregivers in all settings were considered. Two review authors independently assessed the titles and abstracts of retrieved citations. No studies were identified for inclusion. Consequently, no data collection or analysis was possible. No studies met the inclusion criteria, therefore there are no results to report on the use of email for the coordination of healthcare appointments and attendance reminders. No conclusions on the effects of using email for the coordination of healthcare appointments and attendance reminders could be made and thus no recommendations for practice can be stipulated. Given the significant theoretical opportunities that email presents, there is a need for rigorous studies addressing the review question, but this may involve addressing barriers concerning trial development and implementation.

The use of gabapentin in the management of postoperative pain after total hip arthroplasty: a meta-analysis of randomised controlled trials.

PubMed

Han, Chao; Li, Xiao-Dan; Jiang, Hong-Qiang; Ma, Jian-Xiong; Ma, Xin-Long

2016-07-12

Pain management after total hip arthroplasty (THA) varies and has been widely studied in recent years. Gabapentin as a third-generation antiepileptic drug that selectively affects the nociceptive process has been used for pain relief after THA. This meta-analysis was conducted to examine the efficacy of gabapentin in THA. An electronic-based search was conducted using the following databases: PubMed, EMBASE, Ovid MEDLINE, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL). Randomised controlled trials (RCTs) involving gabapentin and a placebo for THA were included. The meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Five trials met the inclusion criteria. The cumulative narcotic consumption and the visual analogue scale (VAS) scores at 24 and 48 h postoperatively were used for postoperative pain assessment. There was a significant decrease in morphine consumption at 24 h (P = 0.00). Compared with the control group, the VAS score (at rest) at 48 h was less in the gabapentin group (P = 0.00). The administration of gabapentin is effective in decreasing postoperative narcotic consumption and the VAS score.

Effects of lifestyle education program for type 2 diabetes patients in clinics: study design of a cluster randomized trial.

PubMed

Adachi, Misa; Yamaoka, Kazue; Watanabe, Mariko; Nishikawa, Masako; Hida, Eisuke; Kobayashi, Itsuro; Tango, Toshiro

2010-11-30

The number of patients with type 2 diabetes is drastically increasing worldwide. It is a serious health problem in Japan as well. Lifestyle interventions can reduce progression from impaired glucose tolerance to type 2 diabetes, and glycemic control has been shown to improve postprandial plasma glucose levels. Moreover, several studies have suggested that continuous interventions (combined diet and exercise) can improve the plasma glucose level and reduce dosage of hypoglycemic agents.Although many interventional studies of lifestyle education for persons with diabetes in hospitals have been reported, only a few have been clinic-based studies employing an evidence-based lifestyle education program. This article describes the design of a cluster randomized controlled trial of the effectiveness of lifestyle education for patients with type 2 diabetes in clinics by registered dietitians. In Japan, general practitioners generally have their own medical clinics to provide medical care for outpatients in the community, including those with type 2 diabetes. With the collaboration of such general practitioners, the study patients were enrolled in the present study. Twenty general practitioners were randomly allocated to each provide patients for entry into either an intervention group (10) or a control group (10). In total, 200 participants will be included in the study. The intervention group will receive intensive education on lifestyle improvement related to type 2 diabetes by registered dietitians in clinics. Lifestyle education will be conducted several times during the study period. The control group will receive information on dietary intake and standard advice on glycemic control by registered dietitians. The primary endpoint is the change from the baseline value of HbA1c at 6 months. Data on health behavior and related issues will be gathered continuously over a 6-month period. This is the first study to evaluate lifestyle education in clinics by a cluster randomization trial in Japan. The proposed study will provide practical information about the usefulness of the intensive lifestyle improvement education program in primary care settings. The study was started in September 2007 and entry of subjects was completed in December 2010. Data on the effect evaluation will be available in 2011. UMIN000004049.

77 FR 38084 - Importer of Controlled Substances; Notice of Registration; Clinical Supplies Management, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-26

... Registration; Clinical Supplies Management, Inc. By Notice dated April 17, 2012, and published in the Federal Register on April 26, 2012, 77 FR 24984, Clinical Supplies Management, Inc., 342 42nd Street South, Fargo..., labeling, and distributing to customers which are qualified clinical sites conducting clinical trials under...

77 FR 75670 - Importer of Controlled Substances; Notice of Registration; Fisher Clinical Services,Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-21

... Registration; Fisher Clinical Services,Inc. By Notice dated September 20, 2012, and published in the Federal Register on October 2, 2012, 77 FR 60143, Fisher Clinical Services, Inc., 7554 Schantz Road, Allentown... company plans to import the listed substances for analytical research and clinical trials. No comments or...

Surgery for congenital choanal atresia.

PubMed

Cedin, Antonio C; Atallah, Alvaro N; Andriolo, Régis B; Cruz, Oswaldo L; Pignatari, Shirley N

2012-02-15

Congenital choanal atresia is a rare abnormality characterized by unilateral or bilateral lack of patency of the posterior end of the nasal cavity. With an incidence of 1:5000 to 1:8000 births, it is twice as prevalent in females as it is in males. Surgical procedures aim to provide adequate functional choanal patency and a low rate of restenosis, avoid harm to any structure in development, enable shorter surgery and hospitalization times, and minimize morbidity and mortality. To evaluate the effectiveness and safety of the available surgical techniques for the treatment of congenital choanal atresia in patients with unilateral and bilateral atresia. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the search was 31 January 2011. We planned to include parallel randomized or quasi-randomized controlled trials testing surgical approaches for the treatment of congenital atresia (irrespective of gender and age) that evaluated normal/adequate respiratory function (self reported or preserved nasal airway) and restenosis as the main primary outcomes. We did not consider reoperation and non-congenital atresia (e.g. traumatic, iatrogenic atresias) for inclusion. Three review authors independently assessed the titles and abstracts of the identified articles to determine potential relevance. For dichotomous and continuous variables, we planned to calculate risk ratios (relative risks; RR) and mean differences (MD) with 95% confidence intervals (CI), respectively. We planned to use the random-effects model since we were expecting substantial clinical and methodological heterogeneity. No randomized controlled trials were identified. From the 120 reports retrieved using our search strategy, 46 primary studies had the potential to be included since they had tested surgical approaches for choanal atresia. However, we excluded all of them during the final selection process because their study designs did not meet our inclusion criteria. There is no definitive evidence, based on randomized controlled trials, to demonstrate the potential advantages and disadvantages of any specific surgical technique for patients with choanal atresia. Specialists should unify their efforts in multicenter randomized controlled trials that test the effectiveness and safety of different surgical techniques in patients with choanal atresia.

The efficacy of a behavioral activation intervention among depressed US Latinos with limited English language proficiency: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Major depressive disorder is highly prevalent among Latinos with limited English language proficiency in the United States. Although major depressive disorder is highly treatable, barriers to depression treatment have historically prevented Latinos with limited English language proficiency from accessing effective interventions. The project seeks to evaluate the efficacy of behavioral activation treatment for depression, an empirically supported treatment for depression, as an intervention that may address some of the disparities surrounding the receipt of efficacious mental health care for this population. Methods/design Following a pilot study of behavioral activation treatment for depression with 10 participants which yielded very promising results, the current study is a randomized control trial testing behavioral activation treatment for depression versus a supportive counseling treatment for depression. We are in the process of recruiting 60 Latinos with limited English language proficiency meeting criteria for major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders 4th and 5th Edition for participation in a single-center efficacy trial. Participants are randomized to receive 10 sessions of behavioral activation treatment for depression (n = 30) or 10 sessions of supportive counseling (n = 30). Assessments occur prior to each session and at 1 month after completing treatment. Intervention targets include depressive symptomatology and the proposed mechanisms of behavioral activation treatment for depression: activity level and environmental reward. We will also examine other factors related to treatment outcome such as treatment adherence, treatment satisfaction, and therapeutic alliance. Discussion This randomized controlled trial will allow us to determine the efficacy of behavioral activation treatment for depression in a fast-growing, yet highly underserved population in US mental health services. The study is also among the first to examine the effect of the proposed mechanisms of change of behavioral activation treatment for depression (that is, activity level and environmental reward) on depression over time. To our knowledge, this is the first randomized controlled trial to compare an empirical-supported treatment to a control supportive counseling condition in a sample of depressed, Spanish-speaking Latinos in the United States. Trial registration Clinical Trials Register: NCT01958840; registered 8 October 2013. PMID:24938081

Water-based exercise for adults with asthma.

PubMed

Grande, Antonio Jose; Silva, Valter; Andriolo, Brenda N G; Riera, Rachel; Parra, Sergio A; Peccin, Maria S

2014-07-17

Asthma is a common condition characterised by airway inflammation and airway narrowing, which can result in intermittent symptoms of wheezing, coughing and chest tightness, possibly limiting activities of daily life. Water-based exercise is believed to offer benefits for people with asthma through pollen-free air, humidity and effects of exercise on physical function. To evaluate the effectiveness and safety of water-based exercise for adults with asthma. We searched the Cochrane Airways Group Specialised Register of Trials (CAGR), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), PsycINFO, the Latin American and Caribbean Health Science Information Database (LILACS), the Physiotherapy Evidence Database (PEDro), the System for Information on Grey Literature in Europe (SIGLE) and Google Scholar on 13 May 2014. We handsearched ongoing clinical trial registers and meeting abstracts of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the British Thoracic Society (BTS). We included all randomised controlled trials (RCTs) of adults with asthma comparing a water-based exercise group versus one or more of the following groups: usual care, land-based exercise, non-exercise. Two review authors (AJG, VS) independently extracted data from the primary studies using a standard form developed for this purpose, which includes methods, participants, interventions and outcomes. We contacted trial authors to request additional data. Data were input by one review author and were double-checked by a second review author. In this systematic review, we provide a narrative synthesis of available evidence from three small studies including 136 adult participants. The studies were at high risk of bias. No meta-analysis was possible because of methodological and interventional heterogeneity between included studies. The primary outcomes of quality of life and exacerbations leading to use of steroids were not reported by these studies. For exacerbations leading to health centre/hospital visits, uncertainty was wide because a very small number of events was reported (in a single study). Secondary outcomes symptoms, lung function, changes in medication and adverse effects, where available, described for each included study. The overall quality of the studies was very low, and no clear differences were noted between water-based exercise and comparator treatments. Therefore, we remain very uncertain about the effects of water-based exercise for adults with asthma. The small number of participants in the three included studies, the clinical and methodological heterogeneity observed and the high risk of bias assessed mean that we are unable to assess the place of water-based exercise in asthma. Randomised controlled trials are needed to assess the efficacy and safety of water-based exercise for adults with asthma. For future research, we suggest greater methodological rigour (participant selection, blinding of outcome assessors, reporting of all outcomes analysed and registering of the study protocol).

Prophylactic antibiotics for the prevention of preterm birth in women at risk: a meta-analysis.

PubMed

Simcox, Rachael; Sin, Wing-To A; Seed, Paul T; Briley, Annette; Shennan, Andrew H

2007-10-01

Preterm birth (PTB) is the major determinant of perinatal morbidity and mortality. Infection is implicated in a large proportion of preterm deliveries, but there is no consensus regarding the efficacy of antibiotic prophylaxis for women at risk. To determine whether antibiotic treatment reduces the risk of preterm delivery in asymptomatic pregnant women at risk of PTB. Relevant publications were identified via electronic searches of MEDLINE (1966 to August 2005), The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Central Register of Controlled Trials (the Cochrane Library, Issue 3, 2005) and PubMed using multiple search terms related to PTB and antibiotics. Publications were limited to randomised controlled trials comparing antibiotics with placebo given to asymptomatic non-labouring women. A random effect model was used, and combined risk ratios calculated for the various risk groups. Associations between treatment effect and the rate of PTB were analysed by meta-regression. Seventeen trials were included, 12 identifying women at risk by abnormal vaginal flora, three on women at high risk from a previous PTB and two recruiting women based on positive fetal fibronectin status. There was no significant association between antibiotic treatment and reduction in PTB irrespective of criteria used to assess risk, the antimicrobial agent administered, or gestational age at time of treatment (overall combined random effect for delivery at less than 37 weeks RR 1.03 (95% CI 0.86-1.24)). Treating women at risk of PTB with antibiotics does not reduce the risk of subsequent PTB.

Systematic review and meta-analysis of studies of the timing of tracheostomy in adult patients undergoing artificial ventilation

PubMed Central

Griffiths, John; Barber, Vicki S; Morgan, Lesley; Young, J Duncan

2005-01-01

Objective To compare outcomes in critically ill patients undergoing artificial ventilation who received a tracheostomy early or late in their treatment. Data sources The Cochrane Central Register of Clinical Trials, Medline, Embase, CINAHL, the National Research Register, the NHS Trusts Clinical Trials Register, the Medical Research Council UK database, the NHS Research and Development Health Technology Assessment Programme, the British Heart Foundation database, citation review of relevant primary and review articles, and expert informants. Study selection Randomised and quasi-randomised controlled studies that compared early tracheostomy with either late tracheostomy or prolonged endotracheal intubation. From 15 950 articles screened, 12 were identified as “randomised or quasi-randomised” controlled trials, and five were included for data extraction. Data extraction Five studies with 406 participants were analysed. Descriptive and outcome data were extracted. The main outcome measure was mortality in hospital. The incidence of hospital acquired pneumonia, length of stay in a critical care unit, and duration of artificial ventilation were also recorded. Random effects meta-analyses were performed. Results Early tracheostomy did not significantly alter mortality (relative risk 0.79, 95% confidence interval 0.45 to 1.39). The risk of pneumonia was also unaltered by the timing of tracheostomy (0.90, 0.66 to 1.21). Early tracheostomy significantly reduced duration of artificial ventilation (weighted mean difference –8.5 days, 95% confidence interval –15.3 to –1.7) and length of stay in intensive care (–15.3 days, –24.6 to –6.1). Conclusions In critically ill adult patients who require prolonged mechanical ventilation, performing a tracheostomy at an earlier stage than is currently practised may shorten the duration of artificial ventilation and length of stay in intensive care. PMID:15901643

The Relaxation Exercise and Social Support Trial (RESST): a community-based randomized controlled trial to alleviate medically unexplained vaginal discharge symptoms.

PubMed

Kobeissi, Loulou; Mahfoud, Ziyad; Khoury, Brigitte; El Kak, Fayssal; Ghantous, Zeina; Khawaja, Marwan; Nakkash, Rima; Ramia, Sami; Zurayk, Huda; Araya, Ricardo; Peters, Tim J

2012-11-09

Symptoms such as medically unexplained vaginal discharge (MUVD) are common and bothersome, leading to potentially unnecessary use of resources. A community-based individually randomized controlled trial to assess the effectiveness of a relatively simple, culturally appropriate multi-component intervention on reducing reported MUVD, among women suffering from low-moderate levels of common mental distress. The setting was a socio-economically deprived, informal settlement in the southern suburbs of Beirut, Lebanon. The intervention comprised up to 12 group sessions implemented over a six-week period, each divided into a psychosocial and a relaxation exercise component. The primary outcome was self-reported MUVD, which was defined as a complaint of vaginal discharge upon ruling out reproductive tract infections (RTIs), through lab analysis. Anxiety and/or depression symptoms were the secondary outcomes for this trial. These were assessed using an Arabic validated version of the Hopkins Symptoms Checklist-25 (HSCL-25). Assessments were done at baseline and six months using face-to face interviews, pelvic examinations and laboratory tests. Women were randomized into either intervention or control group. Blinding on the intervention status was not possible for both logistic and ethical reasons, especially as knowledge of involvement in the intervention was integral to its delivery. Intent to treat analysis was used. Of 75 women randomized to the intervention, 48% reported MUVD at 6 months compared with 63% of 73 in the control group (difference of -15%, 95% confidence interval (CI) -31%, 0%, p=0.067). Adjustments for baseline imbalances and any factors relating to consent had no appreciable effect on these results. The risk of MUVD was reduced in absolute terms by 2.4% for each intervention session attended (95% CI -4.9%, 0.0%, p=0.049). While there was also marginal evidence of a beneficial effect on anxiety, there was no evidence of mediation of the effect on MUVD through measures of common mental disorders. This study confirms that MUVD is an important public health problem. While the benefits of this intervention may appear modest, the intervention offers an opportunity for women to enhance their problem-solving skills as well as use physical relaxation techniques that can help them deal with stressful in their lives. Further research is needed in a variety of contexts, for different populations and preferably involving larger randomized trials of such an intervention. * Title of trial: The Relaxation Exercise and Social Support Trial ISRCTN assigned: ISRCTN98441241 Date of assignation: 10/09/2010 Link: http://www.controlled-trials.com/ISRCTN98441241* Also registered at the Wellcome Trust register:http://www.controlled-trials.com/mrct/trial/469943/98441241.

Anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

PubMed

Solomon, Sharon D; Lindsley, Kristina; Vedula, Satyanarayana S; Krzystolik, Magdalena G; Hawkins, Barbara S

2014-08-29

Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to neovascular AMD accounts for most AMD-related severe vision loss. Anti-vascular endothelial growth factor (anti-VEGF) agents, injected intravitreally, aim to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, improve vision. To investigate: (1) the ocular and systemic effects of, and quality of life associated with, intravitreally injected anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) for the treatment of neovascular AMD compared with no anti-VEGF treatment; and (2) the relative effects of one anti-VEGF agent compared with another when administered in comparable dosages and regimens. We searched Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2014), EMBASE (January 1980 to March 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 27 March 2014. We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or a control treatment (e.g., sham treatment or photodynamic therapy). All trials followed participants for at least one year. Two review authors independently screened records, extracted data, and assessed risks of bias. We contacted trial authors for additional data. We analyzed outcomes as risk ratios (RRs) or mean differences (MDs). We used the standard methodological procedures expected by The Cochrane Collaboration. We included 12 RCTs including a total of 5496 participants with neovascular AMD (the number of participants per trial ranged from 28 to 1208). One trial compared pegaptanib, three trials ranibizumab, and two trials bevacizumab versus controls; six trials compared bevacizumab with ranibizumab. Four trials were conducted by pharmaceutical companies; none of the eight studies which evaluated bevacizumab were funded by pharmaceutical companies. The trials were conducted at various centers across five continents (North and South America, Europe, Asia and Australia). The overall quality of the evidence was very good, with most trials having an overall low risk of bias.When compared with control treatments, participants who received any of the three anti-VEGF agents were more likely to have gained 15 letters or more of visual acuity, lost fewer than 15 letters of visual acuity, and had vision 20/200 or better after one year of follow up. Visual acuity outcomes after bevacizumab and ranibizumab were similar when the same regimens were compared in the same RCTs, despite the substantially lower cost for bevacizumab compared with ranibizumab. No trial directly compared pegaptanib with other anti-VEGF agents; however, when compared with controls, ranibizumab or bevacizumab yielded larger improvements in visual acuity outcomes than pegaptanib.Participants treated with anti-VEGFs showed improvements in morphologic outcomes (e.g., size of CNV or central retinal thickness) compared with participants not treated with anti-VEGF agents. There was less reduction in central retinal thickness among bevacizumab-treated participants than among ranibizumab-treated participants after one year (MD -13.97 μm; 95% confidence interval (CI) -26.52 to -1.41); however, this difference is within the range of measurement error and we did not interpret it as being clinically meaningful.Ocular inflammation and increased intraocular pressure after intravitreal injection were the most frequently reported serious ocular adverse events. Endophthalmitis was reported in fewer than 1% of anti-VEGF treated participants; no cases were reported in control groups. The occurrence of serious systemic adverse events was comparable across anti-VEGF-treated groups and control groups; however, the numbers of events and trial participants may have been insufficient to detect a meaningful difference between groups. Data for visual function, quality of life, and economic outcomes were sparsely measured and reported. The results of this review indicate the effectiveness of anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) in terms of maintaining visual acuity; ranibizumab and bevacizumab were also shown to improve visual acuity. The information available on the adverse effects of each medication do not suggest a higher incidence of potentially vision-threatening complications with intravitreal injection compared with control interventions; however, clinical trial sample sizes may not have been sufficient to detect rare safety outcomes. Research evaluating variable dosing regimens with anti-VEGF agents, effects of long-term use, combination therapies (e.g., anti-VEGF treatment plus photodynamic therapy), and other methods of delivering the agents should be incorporated into future Cochrane reviews.

An optimised patient information sheet did not significantly increase recruitment or retention in a falls prevention study: an embedded randomised recruitment trial.

PubMed

Cockayne, Sarah; Fairhurst, Caroline; Adamson, Joy; Hewitt, Catherine; Hull, Robin; Hicks, Kate; Keenan, Anne-Maree; Lamb, Sarah E; Green, Lorraine; McIntosh, Caroline; Menz, Hylton B; Redmond, Anthony C; Rodgers, Sara; Torgerson, David J; Vernon, Wesley; Watson, Judith; Knapp, Peter; Rick, Jo; Bower, Peter; Eldridge, Sandra; Madurasinghe, Vichithranie W; Graffy, Jonathan

2017-03-28

Randomised controlled trials are generally regarded as the 'gold standard' experimental design to determine the effectiveness of an intervention. Unfortunately, many trials either fail to recruit sufficient numbers of participants, or recruitment takes longer than anticipated. The current embedded trial evaluates the effectiveness of optimised patient information sheets on recruitment of participants in a falls prevention trial. A three-arm, embedded randomised methodology trial was conducted within the National Institute for Health Research-funded REducing Falls with ORthoses and a Multifaceted podiatry intervention (REFORM) cohort randomised controlled trial. Routine National Health Service podiatry patients over the age of 65 were randomised to receive either the control patient information sheet (PIS) for the host trial or one of two optimised versions, a bespoke user-tested PIS or a template-developed PIS. The primary outcome was the proportion of patients in each group who went on to be randomised to the host trial. Six thousand and nine hundred patients were randomised 1:1:1 into the embedded trial. A total of 193 (2.8%) went on to be randomised into the main REFORM trial (control n = 62, template-developed n = 68; bespoke user-tested n = 63). Information sheet allocation did not improve recruitment to the trial (odds ratios for the three pairwise comparisons: template vs control 1.10 (95% CI 0.77-1.56, p = 0.60); user-tested vs control 1.01 (95% CI 0.71-1.45, p = 0.94); and user-tested vs template 0.92 (95% CI 0.65-1.31, p = 0.65)). This embedded methodology trial has demonstrated limited evidence as to the benefit of using optimised information materials on recruitment and retention rates in the REFORM study. International Standard Randomised Controlled Trials Number registry, ISRCTN68240461 . Registered on 01 July 2011.

Regular long-term red blood cell transfusions for managing chronic chest complications in sickle cell disease

PubMed Central

Estcourt, Lise J; Fortin, Patricia M; Hopewell, Sally; Trivella, Marialena; Hambleton, Ian R; Cho, Gavin

2016-01-01

Background Sickle cell disease is a genetic haemoglobin disorder, which can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Sickle cell disease is one of the most common severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. The two most common chronic chest complications due to sickle cell disease are pulmonary hypertension and chronic sickle lung disease. These complications can lead to morbidity (such as reduced exercise tolerance) and increased mortality. This is an update of a Cochrane review first published in 2011 and updated in 2014. Objectives We wanted to determine whether trials involving people with sickle cell disease that compare regular long-term blood transfusion regimens with standard care, hydroxycarbamide (hydroxyurea) any other drug treatment show differences in the following: mortality associated with chronic chest complications; severity of established chronic chest complications; development and progression of chronic chest complications; serious adverse events. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register. Date of the last search: 25 April 2016. We also searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 26 January 2016), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 26 January 2016. Selection criteria We included randomised controlled trials of people of any age with one of four common sickle cell disease genotypes, i.e. Hb SS, Sß0, SC, or Sß+ that compared regular red blood cell transfusion regimens (either simple or exchange transfusions) to hydroxycarbamide, any other drug treatment, or to standard care that were aimed at reducing the development or progression of chronic chest complications (chronic sickle lung and pulmonary hypertension). Data collection and analysis We used the standard methodological procedures expected by Cochrane. Main results No studies matching the selection criteria were found. Authors’ conclusions There is a need for randomised controlled trials looking at the role of long-term transfusion therapy in pulmonary hypertension and chronic sickle lung disease. Due to the chronic nature of the conditions, such trials should aim to use a combination of objective and subjective measures to assess participants repeatedly before and after the intervention. PMID:27198469

External cephalic version for breech presentation before term.

PubMed

Hutton, E K; Hofmeyr, G J

2006-01-25

External cephalic version (ECV) of the breech fetus at term (after 37 weeks) has been shown to be effective in reducing the number of breech presentations and caesarean sections, but the rates of success are relatively low. This review examines studies initiating ECV prior to term (before 37 weeks' gestation). To assess the effectiveness of a policy of beginning ECV before term (before 37 weeks' gestation) for breech presentation on fetal presentation at birth, method of delivery, and the rate of preterm birth, perinatal morbidity, stillbirth or neonatal mortality. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2005), MEDLINE (1965 to April 2005), EMBASE (1988 to April 2005), and Controlled Clinical Trials randomised controlled trials registry (April 2005). Randomised trials of ECV beginning before term (before 37 weeks' gestation) compared with a control group in women with breech presentation before term. Two review authors independently assessed eligibility and trial quality and extracted data. Three studies are included. One study reported on ECV that was undertaken and completed before 37 weeks' gestation compared to no ECV. No difference was found in the rate of non-cephalic presentation at birth. One study reported on a policy of ECV that was initiated before term (33 weeks) and up until 40 weeks' gestation and which could be repeated up until delivery compared to no ECV. This study showed a decrease in the rate of non-cephalic presentation at birth (relative risk 0.59, 95% confidence interval 0.45 to 0.77). One study reported on ECV started at between 34 to 35 weeks' gestation compared to beginning at 37 to 38 weeks' gestation. Although findings were not statistically significant, a 9.5% decrease in the rate of non-cephalic presentation at birth and a 7% decrease in the caesarean section rate were reported when ECV was started early. Compared with no ECV attempt, ECV commenced before term reduces non-cephalic births. Compared with ECV at term, beginning ECV at between 34 to 35 weeks may have some benefit in terms of decreasing the rate of non-cephalic presentation, and caesarean section. Further trials are needed to confirm this finding and to rule out increased rates of preterm birth, or other adverse perinatal outcomes. A large pragmatic trial is ongoing (www.utoronto.ca/miru/eecv2).

Brazilian medicinal plants to treat upper respiratory tract and bronchial illness: systematic review and meta-analyses-study protocol.

PubMed

Lopes, Luciane C; Silva, Maria Carolina O; Motta, Cristiane Bergamashi; Macho Quirós, Antonio; Biavatti, Maique Weber; de Oliveira, Jardel Corrêa; Guyatt, Gordon

2014-07-23

Respiratory illness, often associated with cough and sputum, is frequent. In Brazil, herbal medicines are often recommended as a first-line treatment for respiratory illness. There exists uncertainty regarding the effectiveness of these treatments. No systematic review has evaluated Brazilian medicinal plants (BMP) to treat upper respiratory tract and bronchial illness (URTI). We will conduct a systematic review and, if appropriate, a series of meta-analyses evaluating the safety and effectiveness of BMP for URTI. Eligible randomised controlled trials and observational studies will enrol adult or paediatric patients presenting with URTI treated by BMP approved by the Brazilian Health Surveillance Agency compared with placebo, no treatment or an alternative therapy. Our search will include the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Illness Group's Specialized Register; MEDLINE; EMBASE; CINAHL (Cumulative Index to Nursing and Allied Health Literature); Web of Science; AMED; LILACS; CAB abstracts; clinical trial.gov; the WHO Trial Register and the Brazilian thesis database (CAPES) without any language restrictions. Outcomes of interest are time to resolution of clinical symptoms and/or signs (cough, sputum production or activity limitations), severity of symptoms prior to resolution and major/minor adverse events. Teams of reviewers will, independently and in duplicate, screen titles and abstracts and the complete full text to determine eligibility. For eligible studies, reviewers will perform data abstraction and assess risk of bias of eligible trials. When appropriate, we will conduct meta-analyses. We will also assess the quality of body of evidence (confidence in estimates of effect) for each of the outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The systematic review will be published in a peer-reviewed journal. Brief reports of review findings will be disseminated directly to appropriate audiences via email and other modes of communication. The review will guide healthcare practice and policy in Brazil. Prospero CRD42014007057. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Clinical Tests Testing New Therapies for Stargardt Disease].

PubMed

Kousal, B; Ďuďáková, Ľ; Hlavatá, L; Lišková, P

2016-02-01

To provide information on currently ongoing clinical trials for Stargardt disease. We have searched the clinical trial register (www.clinicaltrials.gov) for the keyword "Stargardt" and list active ongoing studies. There are currently eight registered clinical trials enrolling patients with Stargardt disease; all in phase I or II aiming at four mechanisms of action: inhibition of the production of vitamin A toxic dimers, gene therapy restoring wild type transcription of the ABCA4 gene, neuroprotection preventing retinal cells from oxidative damage, and replacement of the damaged retinal pigment epithelium using stem cell therapy. The basic prerequisite for enrolment in the vast majority of clinical trials is confirmation of the clinical diagnosis by mutational analysis. The wide variety of therapies that are registered as clinical trials for Stargardt disease significantly raises the possibility that effective treatments will be available in the near future for this currently incurable condition and that molecular genetic testing should be increasingly considered. Stargardt disease, clinical trial, ABCA4, mutation.

Effectiveness of Azadirachta indica (neem) mouthrinse in plaque and gingivitis control: a systematic review.

PubMed

Dhingra, K; Vandana, K L

2017-02-01

The aim of this systematic review was to evaluate the effectiveness of Azadirachta indica (neem)-based herbal mouthrinse in improving plaque control and gingival health. Literature search was accomplished using electronic databases (PubMed, Cochrane Central Register of Controlled Trials and EMBASE) and manual searching, up to February 2015, for randomized controlled trials (RCTs) presenting clinical data for efficacy of neem mouthrinses when used alone or as an adjunct to mechanical oral hygiene as compared to chlorhexidine mouthrinses for controlling plaque and gingival inflammation in patients with gingivitis. Of the total 206 articles searched, three randomized controlled trials evaluating neem-based herbal mouthrinses were included. Due to marked heterogeneity observed in study characteristics, meta-analysis was not performed. These studies reported that neem mouthrinse was as effective as chlorhexidine mouthrinse when used as an adjunct to toothbrushing in reducing plaque and gingival inflammation in gingivitis patients. However, the quality of reporting and evidence along with methods of studies was generally flawed with unclear risk of bias. Despite the promising results shown in existing randomized controlled trials, the evidence concerning the clinical use of neem mouthrinses is lacking and needs further reinforcement with high-quality randomized controlled trials based on the reporting guidelines of herbal CONSORT statement. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Garlic for the common cold.

PubMed

Lissiman, Elizabeth; Bhasale, Alice L; Cohen, Marc

2012-03-14

Garlic is alleged to have antimicrobial and antiviral properties that relieve the common cold, among other beneficial effects. There is widespread usage of garlic supplements. The common cold is associated with significant morbidity and economic consequences. On average, children have six to eight colds per year and adults have two to four. To determine whether garlic (allium sativum) is effective for either the prevention or treatment of the common cold, when compared to placebo, no treatment or other treatments. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 4), which includes the Cochrane Acute Respiratory Infections Group Specialised Register, OLDMEDLINE (1950 to 1965), MEDLINE (January 1966 to November week 3, 2011), EMBASE (1974 to December 2011) and AMED (1985 to December 2011). Randomised controlled trials of common cold prevention and treatment comparing garlic with placebo, no treatment or standard treatment. Two review authors independently reviewed and selected trials from searches, assessed and rated study quality and extracted relevant data. Of the six trials identified as potentially relevant from our searches, only one trial met the inclusion criteria. This trial randomly assigned 146 participants to either a garlic supplement (with 180 mg of allicin content) or a placebo (once daily) for 12 weeks. The trial reported 24 occurrences of the common cold in the garlic intervention group compared with 65 in the placebo group (P < 0.001), resulting in fewer days of illness in the garlic group compared with the placebo group (111 versus 366). The number of days to recovery from an occurrence of the common cold was similar in both groups (4.63 versus 5.63). Only one trial met the inclusion criteria, therefore limited conclusions can be drawn. The trial relied on self reported episodes of the common cold but was of reasonable quality in terms of randomisation and allocation concealment. Adverse effects included rash and odour. There is insufficient clinical trial evidence regarding the effects of garlic in preventing or treating the common cold. A single trial suggested that garlic may prevent occurrences of the common cold but more studies are needed to validate this finding. Claims of effectiveness appear to rely largely on poor-quality evidence.

Characteristics and publication patterns of obstetric studies registered in ClinicalTrials.gov.

PubMed

Stockmann, Chris; Sherwin, Catherine M T; Koren, Gideon; Campbell, Sarah C; Constance, Jonathan E; Linakis, Matthew; Balch, Alfred; Varner, Michael W; Spigarelli, Michael G

2014-04-01

Physiologic changes during pregnancy alter the pharmacokinetics, safety, and efficacy of many drugs. For clinicians, there is often uncertainty regarding the safety of these drugs due to a scarcity of published data. This study aimed to comprehensively evaluate the characteristics and publication patterns of obstetric studies registered in ClinicalTrials.gov from 2007 to 2012. Primary outcome measures, funding sources, inclusion criteria, and the reporting of study results were evaluated. A manual review of Medline/PubMed was performed to identify publications associated with studies registered in ClinicalTrials.gov. Of 93,709 total studies, there were 5,203 (6%) obstetric studies registered in ClinicalTrials.gov. Interventional studies accounted for 70% and 30% were observational. Clinical trials of drugs (49%), procedures (13%), and behavioral interventions (12%) were most common. Among interventional drug trials, 84% featured randomized allocation to study arms and 93% included measures of safety and/or efficacy as primary endpoints. Of 946 (18%) studies completed more than 2 years ago, only 11% had reported results and <7% had been published. In an area with a great need for evidence of safe and effective therapies, the low publication rate of completed studies incorporating elements of high-quality trial design is concerning. The sources of this trend should be closely investigated. © 2013, The American College of Clinical Pharmacology.

Effect Sizes and Primary Outcomes in Large-Budget, Cardiovascular-Related Behavioral Randomized Controlled Trials Funded by NIH Since 1980

PubMed Central

Irvin, Veronica L.; Kaplan, Robert M.

2015-01-01

Purpose We reviewed large-budget, National Institutes of Health (NIH)-supported randomized controlled trials (RCTs) with behavioral interventions to assess (1) publication rates, (2) trial registration, (3) use of objective measures, (4) significant behavior and physiological change, and (5) effect sizes. Methods We identified large-budget grants (>$500,000/year) funded by NIH (National Heart Lung and Blood Institute (NHLBI) or National Institute of Diabetes & Digestive and Kidney Diseases (NIDDK)) for cardiovascular disease (dates January 1, 1980 to December 31, 2012). Among 106 grants that potentially met inclusion criteria, 20 studies were not published and 48 publications were excluded, leaving 38 publications for analysis. ClinicalTrials.gov abstracts were used to determine whether outcome measures had been pre-specified. Results Three fourths of trials were registered in ClinicalTrials.gov and all published pre-specified outcomes. Twenty-six trials reported a behavioral outcome with 81 % reporting significant improvements for the target behavior. Thirty-two trials reported a physiological outcome. All were objectively measured, and 81 % reported significant benefit. Seventeen trials reported morbidity outcomes, and seven reported a significant benefit. Nine trials assessed mortality, and all were null for this outcome. Conclusions Behavioral trials complied with trial registration standards. Most reported a physiological benefit, but few documented morbidity or mortality benefits. PMID:26507906

Electroacupuncture plus moxibustion therapy for patients with major depressive disorder: study protocol for a randomized controlled trial.

PubMed

Kim, Mikyung; Choi, Eun-Ji; Kim, Sung-Phil; Kim, Jung-Eun; Park, Hyo-Ju; Kim, Ae-Ran; Seo, Bok-Nam; Kwon, O-Jin; Cho, Jung Hyo; Chung, Sun-Yong; Kim, Joo-Hee

2017-01-13

Major depressive disorder (MDD) is one of the most prevalent mental health disorders and has a significant societal economic burden. Antidepressants and cognitive behavioral therapy are two primary interventions for the standardized treatment of MDD. However, their weaknesses, such as a low response rate, a high risk of adverse events from medication, and the high cost of cognitive behavioral therapy, have resulted in a need for complementary and alternative medicine (CAM). Among the various therapeutic interventions in CAM, electroacupuncture and moxibustion have been widely used to treat various mental illnesses, including MDD. The aim of this study is to evaluate the feasibility of conducting a full-scale randomized controlled trial to investigate the efficacy and safety of electroacupuncture plus moxibustion therapy for MDD. We will include patients between the ages of 19 to 65 years with MDD. A total of 30 participants will be recruited, and they will be randomly allocated into two groups at a 1:1 ratio. Patients in the treatment and control groups will, respectively, receive real and sham electroacupuncture/moxibustion treatments, for a total of 20 sessions over 8 weeks. The primary outcome will be the Hamilton Rating Scale for Depression, and the secondary outcomes will be Beck's Depression Inventory, the Insomnia Severity Index, the State-Trait Anxiety Inventory, the EuroQol 5-Dimension Index, the Measure Yourself Medical Outcome Profile version 2, and electroencephalography. Adverse events will be monitored at each visit to assess safety. All outcomes will be assessed and analyzed by researchers blinded to the treatment allocation. This is a two-armed, parallel-design, patient-assessor blinded, multicenter, randomized, sham-controlled pilot clinical trial. Data will be analyzed before and after treatment and during a 4-week follow-up. The results of the trial will provide a basis for further studies assessing the efficacy and safety of electroacupuncture plus moxibustion treatment for MDD. Korean Clinical Trial Registry, CRIS-KCT0001810 . Registered on 5 February 2016 (retrospectively registered; date of enrollment of the first participant to the trial: 2 December 2015).

Frequency of pneumothorax and haemothorax after primary open versus closed implantation strategies for insertion of a totally implantable venous access port in oncological patients: study protocol for a randomised controlled trial.

PubMed

Hüttner, Felix J; Bruckner, Tom; Alldinger, Ingo; Hennes, Roland; Ulrich, Alexis; Büchler, Markus W; Diener, Markus K; Knebel, Phillip

2015-03-31

The insertion of central venous access devices, such as totally implantable venous access ports (TIVAPs), is routine in patients who need a safe and permanent venous access. The number of port implantations is increasing due to the development of innovative adjuvant and neo-adjuvant therapies. Currently, two different strategies are being routinely used: surgical cut-down of the cephalic vein (vena section) and direct puncture of the subclavian vein. The aim of this trial is to identify the strategy for the implantation of TIVAPs with the lowest risk of pneumothorax and haemothorax. The PORTAS-3 trial is designed as a multicentre, randomised controlled trial to compare two implantation strategies. A total of 1,154 patients will be randomised after giving written informed consent. Patients must be over 18 years of age and scheduled for primary implantation of a TIVAP on the designated side. The primary endpoint will be the frequency of pneumothorax and haemothorax after insertion of a TIVAP by one of two different strategies. The experimental intervention is as follows: open strategy, defined as surgical cut-down of the cephalic vein, supported by a rescue technique if necessary, and in the case of failure, direct puncture of the subclavian vein. The control intervention is as follows: direct puncture of the subclavian vein using the Seldinger technique guided by sonography, fluoroscopy or landmark technique. The trial duration is approximately 36 months, with a recruitment period of 18 months and a follow-up period of 30 days. The PORTAS-3 trial will compare two different TIVAP implantation strategies with regard to their individual risk of postoperative pneumothorax and haemothorax. Since TIVAP implantation is one of the most common procedures in general surgery, the results will be of interest for a large community of surgeons as well as oncologists and general practitioners. The pragmatic trial design ensures that the results will be generalizable to a wide range of patients. The trial protocol was registered on 28 August 2014 with the German Clinical Trials Register (DRKS00004900) . The World Health Organization's Universal Trial Number is U1111-1142-4420.

Vitamin supplementation for preventing miscarriage.

PubMed

Rumbold, A; Middleton, P; Crowther, C A

2005-04-18

Miscarriage is a common complication of pregnancy that can be caused by a wide range of factors. Poor dietary intake of vitamins has been associated with an increased risk of miscarriage, therefore supplementing women with vitamins either prior to or in early pregnancy may help prevent miscarriage. The objectives of this review are to determine the effectiveness and safety of any vitamin supplementation, on the risk of spontaneous miscarriage, maternal adverse outcomes and fetal and infant adverse outcomes. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (8 September 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003) and MEDLINE (1966 to May 2003), Current Contents (1998 to May 2003) and EMBASE (1980 to May 2003). All randomised and quasi-randomised trials comparing one or more vitamins with either placebo, other vitamins, no vitamins or other interventions, prior to conception, periconceptionally or in early pregnancy (less than 20 weeks' gestation). Two review authors independently assessed trials for inclusion, extracted data and assessed trial quality. We identified seventeen trials assessing supplementation with any vitamin(s) starting prior to 20 weeks' gestation and reporting at least one primary outcome that were eligible for the review. Overall, the included trials involved 35,812 women and 37,353 pregnancies. Two trials were cluster randomised and contributed data for 20,758 women and 22,299 pregnancies in total. No difference was seen between women taking any vitamins compared with controls for total fetal loss (relative risk (RR) 1.05, 95% confidence interval (CI) 0.95 to 1.15), early or late miscarriage (RR 1.08, 95% CI 0.95 to 1.24) or stillbirth (RR 0.85, 95% CI 0.63 to 1.14) and most of the other primary outcomes, using fixed-effect models. For the other primary outcomes, women given any type of vitamin(s) compared with controls were less likely to develop pre-eclampsia (RR 0.68, 95% CI 0.54 to 0.85, four trials, 5580 women) and more likely to have a multiple pregnancy (RR 1.38, 95% CI 1.12 to 1.70, three trials, 20,986 women). Taking vitamin supplements, alone or in combination with other vitamins, prior to pregnancy or in early pregnancy, does not prevent women experiencing miscarriage or stillbirth. However, women taking vitamin supplements may be less likely to develop pre-eclampsia and more likely to have a multiple pregnancy.

The Quality of Registration of Clinical Trials: Still a Problem

PubMed Central

Viergever, Roderik F.; Karam, Ghassan; Reis, Andreas; Ghersi, Davina

2014-01-01

Introduction The benefits of clinical trials registration include improved transparency on clinical trials for healthcare workers and patients, increased accountability of trialists, the potential to address publication bias and selective reporting, and possibilities for research collaboration and prioritization. However, poor quality of information in registered records of trials has been found to undermine these benefits in the past. Trialists' increasing experience with trial registration and recent developments in registration systems may have positively affected data quality. This study was conducted to investigate whether the quality of registration has improved. Methods We repeated a study from 2009, using the same methods and the same research team. A random sample of 400 records of clinical trials that were registered between 01/01/2012 and 01/01/2013 was taken from the International Clinical Trials Registry Platform (ICTRP) and assessed for the quality of information on 1) contact details, 2) interventions and 3) primary outcomes. Results were compared to the equivalent assessments from our previous study. Results There was a small and not statistically significant increase from 81.0% to 85.5% in the percentage of records that provided a name of a contact person. There was a significant increase from 68.7% to 74.9% in the number of records that provided either an email address or a telephone number. There was a significant increase from 44.2% to 51.9% in the number of intervention arms that were complete in registering intervention specifics. There was a significant increase from 38.2% to 57.6% in the number of primary outcomes that were specific measures with a meaningful timeframe. Approximately half of all trials continued to be retrospectively registered. Discussion There have been small but significant improvements in the quality of registration since 2009. Important problems with quality remain and continue to constitute an impediment to the meaningful utilization of registered trial information. PMID:24427293

Lack of high-quality studies comparing the effectiveness, and cost-effectiveness, of dental auxiliaries and dentists in performing dental care.

PubMed

Richards, Derek

2014-09-01

Cochrane Effective Practice and Organisation of Care (EPOC) Group's Specialised Register; Cochrane Oral Health Group's Specialised Register; the Cochrane Central Register of Controlled Trials Medline; Embase; CINAHL; Cochrane Database of Systematic Reviews; Database of Abstracts of Reviews of Effectiveness; five other databases and two trial registries. A number of dental journals were hand-searched and a grey literature search preformed. Randomised controlled trials (RCTs), non-randomised controlled trials (NRCTs), controlled before and after studies (CBAs) and interrupted time series (ITSs) were considered. Selection was conducted independently by two reviewers. Three reviewers extracted data and assessed risk of bias. Meta-analysis was not possible so a narrative summary was presented. Five studies (one cluster RCT, three RCTs and one NRCT) were included. All the studies were at high risk of bias and the overall quality of evidence was very low. The majority of the studies were more than 20 years old.Four studies evaluated sealant placement; three found no evidence of a difference in retention rates of those placed by dental auxiliaries and dentists over a range of follow-up periods (six to 24 months). One study found that sealants placed by a dental auxiliary had lower retention rates than ones placed by a dentist after 48 months (9.0% with auxiliary versus 29.1% with dentist); but the net reduction in the number of teeth exhibiting caries was lower for teeth treated by the dental auxiliary than the dentist (three with auxiliary versus 60 with dentist, P value < 0.001). One study showed no evidence of a difference in dental decay after treatment with fissure sealants between groups. One study comparing the effectiveness of dental auxiliaries and dentists performing ART reported no difference in survival rates of the restorations (fillings) after 12 months. We only identified five studies for inclusion in this review, all of which were at high risk of bias, and four were published more than 20 years ago, highlighting the paucity of high-quality evaluations of the relative effectiveness, cost-effectiveness and safety of dental auxiliaries compared with dentists in performing clinical tasks. No firm conclusions could be drawn from the present review about the relative effectiveness of dental auxiliaries and dentists.

Adrenaline auto-injectors for the treatment of anaphylaxis with and without cardiovascular collapse in the community.

PubMed

Sheikh, Aziz; Simons, F Estelle R; Barbour, Victoria; Worth, Allison

2012-08-15

Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may cause death. Adrenaline (epinephrine) auto-injectors are recommended as the initial, potentially life-saving treatment of choice for anaphylaxis in the community, but they are not universally available and have limitations in their use. To assess the effectiveness of adrenaline (epinephrine) auto-injectors in relieving respiratory, cardiovascular, and other symptoms during episodes of anaphylaxis that occur in the community. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1), MEDLINE (Ovid SP) (1950 to January 2012), EMBASE (Ovid SP) (1980 to January 2012 ), CINAHL (EBSCO host) (1982 to January 2012 ), AMED (EBSCO host) (1985 to January 2012 ), LILACS, (BIREME) (1980 to January 2012 ), ISI Web of Science (1950 to January 2012 ). We adapted our search terms for other databases. We also searched websites listing on-going trials: the World Health Organization International Clinical Trials Registry Platform, the UK Clinical Research Network Study Portfolio, and the meta Register of Controlled Trials; and contacted pharmaceutical companies who manufacture adrenaline auto-injectors in an attempt to locate unpublished material. Randomized and quasi-randomized controlled trials comparing auto-injector administration of adrenaline with any control including no intervention, placebo, or other adrenergic agonists were eligible for inclusion. Two authors independently assessed articles for inclusion. None of the 1328 studies that were identified satisfied the inclusion criteria. Based on this review, we cannot make any new recommendations on the effectiveness of adrenaline auto-injectors for the treatment of anaphylaxis. Although randomized, double-blind, placebo-controlled clinical trials of high methodological quality are necessary to define the true extent of benefits from the administration of adrenaline in anaphylaxis via an auto-injector, such trials are unlikely to be performed in individuals experiencing anaphylaxis because of ethical concerns associated with randomization to placebo. There is, however, a need to consider trials in which, for example, auto-injectors of different doses of adrenaline and differing devices are compared in order to provide greater clarity on the dose and device of choice. Such trials would be practically challenging to conduct. In the absence of appropriate trials, we recommend that adrenaline administration by auto-injector should still be regarded as the most effective first-line treatment for the management of anaphylaxis in the community. In countries where auto-injectors are not commonly used, it may be possible to conduct trials to compare administration of adrenaline via auto-injector with adrenaline administered by syringe and ampoule, or comparing the effectiveness of two different types of auto-injector.

Internet-delivered cognitive behaviour therapy for depression in people with diabetes: study protocol for a randomised controlled trial.

PubMed

Robins, Lisa; Newby, Jill; Wilhelm, Kay; Smith, Jessica; Fletcher, Therese; Ma, Trevor; Finch, Adam; Campbell, Lesley; Andrews, Gavin

2015-01-01

Depression substantially contributes to the personal burden and healthcare costs of living with diabetes mellitus (DM). Comorbid depression and DM are associated with poorer quality of life, poorer self-management and glycemic control, increased risk for DM complications and higher mortality rates, and higher health service utilization. Depression remains under-recognized and undertreated in people with DM, which may, in part, result from barriers associated with accessing face-to-face treatment. This study will examine the efficacy of an internet-based cognitive behaviour therapy programme for major depressive disorder (iCBT-MDD) in people with DM. A CONSORT 2010 compliant, registered randomised controlled trial of the intervention (iCBT-MDD) versus a treatment as usual control group will be conducted. The study will include 100 adults aged 18 years and over with a diagnosis of type 1 or type 2 DM and self-reported symptoms that satisfy MDD which will enable us to detect a statistically significant difference with a group effect size of 0.6 at a power of 80% and significance level of p=0.05. Participants will be randomised to receive the iCBT-MDD programme immediately, or to wait 10 weeks before accessing the programme. Primary outcomes will be self-reported depression severity, DM-related distress, and glycemic control (glycosylated hemoglobin). Secondary outcomes will be general distress and disability, generalized anxiety, lifestyle behaviours, somatization, eating habits, alcohol use, and acceptability of the iCBT programme to participants, and practicality for clinicians. Data will be analyzed with linear mixed models for each outcome measure. The Human Research Ethics Committee of St Vincent's Hospital Australia have given ethics approval (HREC/13/SVH/291). Results will be disseminated via peer-reviewed publication and social media channels of Australian Diabetes Consumer Representative Bodies. The trial is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12613001198718).

Electromechanical and robot-assisted arm training for improving generic activities of daily living, arm function, and arm muscle strength after stroke.

PubMed

Mehrholz, Jan; Hädrich, Anja; Platz, Thomas; Kugler, Joachim; Pohl, Marcus

2012-06-13

Electromechanical and robot-assisted arm training devices are used in rehabilitation, and might help to improve arm function after stroke. To assess the effectiveness of electromechanical and robot-assisted arm training for improving generic activities of daily living, arm function, and arm muscle strength in patients after stroke. We will also assess the acceptability and safety of the therapy. We searched the Cochrane Stroke Group's Trials Register (last searched July 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 7), MEDLINE (1950 to July 2011), EMBASE (1980 to July 2011), CINAHL (1982 to July 2011), AMED (1985 to July 2011), SPORTDiscus (1949 to July 2011), PEDro (searched August 2011), COMPENDEX (1972 to July 2011), and INSPEC (1969 to July 2011). We also handsearched relevant conference proceedings, searched trials and research registers, checked reference lists, and contacted trialists, experts and researchers in our field, as well as manufacturers of commercial devices. Randomised controlled trials (RCTs) comparing electromechanical and robot-assisted arm training for recovery of arm function with other rehabilitation or placebo interventions, or no treatment, for patients after stroke. Two review authors independently selected trials for inclusion, assessed trial quality, and extracted data. We contacted trialists for additional information. We analysed the results as standardised mean differences (SMDs) for continuous variables and risk differences (RDs) for dichotomous variables. We included 19 trials (involving 666 participants) in this update of our review. Electromechanical and robot-assisted arm training did improve activities of daily living (SMD 0.43, 95% confidence interval (CI) 0.11 to 0.75, P = 0.009, I(2) = 67%) as well as arm function (SMD 0.45, 95% CI 0.20 to 0.69, P = 0.0004, I(2) = 45%), but arm muscle strength did not improve (SMD 0.48, 95% CI -0.06 to 1.03, P = 0.08, I(2) = 79%). Electromechanical and robot-assisted arm training did not increase the risk of patients to drop out (RD 0.00, 95% CI -0.04 to 0.04, P = 0.82, I(2) = 0.0%), and adverse events were rare. Patients who receive electromechanical and robot-assisted arm training after stroke are more likely to improve their generic activities of daily living. Paretic arm function may also improve, but not arm muscle strength. However, the results must be interpreted with caution because there were variations between the trials in the duration and amount of training, type of treatment, and in the patient characteristics.

Fluoride gel effective at reducing caries in children.

PubMed

Richards, Derek

2015-12-01

Data Cochrane Oral Health Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline , Embase, CINAHL, LILACS, ProQuest Dissertations and Theses, the Web of Science Conference Proceedings, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Randomised or quasi-randomised controlled trials comparing topically applied fluoride gel with placebo or no treatment in children up to 16 years were considered. Studies had to be at least one year in duration with a frequency of application of at least once a year with blind outcome assessment. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces in both permanent and primary teeth (D(M)FS and d(e/m)fs). At least two reviewers extracted data and assessed risk of bias. The primary measure of effect was the prevented fraction (PF). Where data could be pooled random-effects meta-analyses were conducted. Potential sources of heterogeneity were examined in random-effects meta-regression analyses. Twenty-eight trials involving 9140 children and adolescents were included. Most of the studies (20) were at high risk of bias, with eight at unclear risk of bias. Twenty-five trials (8479 participants) provided data for meta-analysis on permanent teeth, with a D(M)FS pooled prevented fraction (PF) estimate of 28% (95% CI; 19-36%; P < 0.0001; with substantial heterogeneity (P < 0.0001; I(2) = 82%); moderate quality evidence). Subgroup and metaregression analyses suggested no significant association between estimates of D(M)FS prevented fractions and the prespecified trial characteristics. However, the effect of fluoride gel varied according to the type of control group used, with D(M)FS PF on average being 17% (95% CI 3% to 31%; P = 0.018) higher in non-placebo-controlled trials (the reduction in caries was 38% (95% CI 24% to 52%; P < 0.0001, 2808 participants) for the ten trials with no treatment as control group, and 21% (95% CI 15% to 28%; P < 0.0001, 5671 participants) for the 15 placebo-controlled trials.A funnel plot of the 25 trials in the D(M)FS PF meta-analysis indicated a relationship between prevented fraction and study precision, with an apparent lack of small studies with statistically significant large effects.For primary teeth the d(e/m)fs pooled prevented fraction estimate for the three trials (1254 participants) = 20% (95%CI; 1% - 38%; P = 0.04; with no heterogeneity (P = 0.54; I(2) = 0%); low quality evidence).There was limited reporting of adverse events. Only two trials reported information on acute toxicity signs and symptoms during the application of the gel (risk difference 0.01, 95% CI -0.01 to 0.02; P = 0.36; with no heterogeneity (P = 36; I(2) = 0%); 490 participants; very low quality evidence). None of the trials reported information on tooth staining, mucosal irritation or allergic reaction. The conclusions of this updated review remain the same as those when it was first published. There is moderate quality evidence of a large caries-inhibiting effect of fluoride gel in the permanent dentition. Information concerning the caries-preventive effect of fluoride gel on the primary dentition, which also shows a large effect, is based on low quality evidence from only three placebo-controlled trials. There is little information on adverse effects or on acceptability of treatment. Future trials should include assessment of potential adverse effects.

The effectiveness and cost-effectiveness of a mindfulness training programme in schools compared with normal school provision (MYRIAD): study protocol for a randomised controlled trial.

PubMed

Kuyken, Willem; Nuthall, Elizabeth; Byford, Sarah; Crane, Catherine; Dalgleish, Tim; Ford, Tamsin; Greenberg, Mark T; Ukoumunne, Obioha C; Viner, Russell M; Williams, J Mark G

2017-04-26

Mindfulness-based approaches for adults are effective at enhancing mental health, but few controlled trials have evaluated their effectiveness or cost-effectiveness for young people. The primary aim of this trial is to evaluate the effectiveness and cost-effectiveness of a mindfulness training (MT) programme to enhance mental health, wellbeing and social-emotional behavioural functioning in adolescence. To address this aim, the design will be a superiority, cluster randomised controlled, parallel-group trial in which schools offering social and emotional provision in line with good practice (Formby et al., Personal, Social, Health and Economic (PSHE) Education: A mapping study of the prevalent models of delivery and their effectiveness, 2010; OFSTED, Not Yet Good Enough: Personal, Social, Health and Economic Education in schools, 2013) will be randomised to either continue this provision (control) or include MT in this provision (intervention). The study will recruit and randomise 76 schools (clusters) and 5700 school students aged 12 to 14 years, followed up for 2 years. The study will contribute to establishing if MT is an effective and cost-effective approach to promoting mental health in adolescence. International Standard Randomised Controlled Trials, identifier: ISRCTN86619085 . Registered on 3 June 2016.

Implantable miniature telescope (IMT) for vision loss due to end-stage age-related macular degeneration.

PubMed

Gupta, Amisha; Lam, Jessica; Custis, Peter; Munz, Stephen; Fong, Donald; Koster, Marguerite

2018-05-30

Age-related macular degeneration (AMD) causes progressive and irreversible damage to the retina, resulting in loss of central vision. AMD is the third leading cause of irreversible visual impairment worldwide and the leading cause of blindness in industrialized countries. Since AMD is more common in older individuals, the number of affected individuals will increase significantly as the population ages. The implantable miniature telescope (IMT) is an ophthalmic device developed to improve vision in individuals who have lost vision due to AMD. Once implanted, the IMT is used to enlarge objects in the central visual field and focus them onto healthy areas of the retina not affected by AMD, allowing individuals to recognize objects that they otherwise could not see. It is unclear whether and how much the IMT can improve vision in individuals with end-stage AMD. To assess the effectiveness and safety of the IMT in improving visual acuity and quality of life in people with late or advanced AMD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 11); Ovid MEDLINE; Embase.com; PubMed; LILACS; AMED; Web of Science Conference Proceedings Citation Index-Science; OpenSIGLE; the metaRegister of Controlled Trials (mRCT) (last searched 27 June 2014); ClinicalTrials.gov; the ICTRP and the US Food and Drug Administration (FDA) Medical Devices database. The date of the search was 2 November 2017, with the exception of mRCT which is no longer in service. We planned to include randomized controlled trials (RCTs) and quasi-randomized trials that compared the IMT versus no IMT. Two review authors independently assessed all studies for inclusion, using standard methodological procedures expected by Cochrane. Our search yielded 1042 unique records. We removed irrelevant studies after screening titles and abstracts, and evaluated five full-text reports from four studies; three were non-randomized studies. There was one ongoing RCT that compared the OriLens intraocular telescope with standard low vision training in eyes with end-stage AMD. Results for this study are expected in 2020. We found no RCT or quasi-RCT and can draw no conclusion about the effectiveness and safety of the IMT in improving visual acuity in individuals with late or advanced AMD. Since the IMT is typically implanted monocularly based upon which eye has better best-corrected distance visual acuity, randomization between eyes within an individual may not be acceptable. Studies are needed that compare outcomes between individuals randomized to the device versus individuals not implanted, at least during study follow-up, who serve as controls.

A phase III, multi-centre, double-masked randomised controlled trial of adjunctive intraocular and peri-ocular steroid (triamcinolone acetonide) versus standard treatment in eyes undergoing vitreoretinal surgery for open globe trauma (ASCOT): statistical analysis plan.

PubMed

Lo, Jessica W; Bunce, Catey; Charteris, David; Banerjee, Philip; Phillips, Rachel; Cornelius, Victoria R

2016-08-02

Open globe ocular trauma complicated by intraocular scarring (proliferative vitreoretinopathy) is a relatively rare, blinding, but potentially treatable condition for which, at present, surgery is often unsatisfactory and visual results frequently poor. To date, no pharmacological adjuncts to surgery have been proven to be effective. The aim of the Adjunctive Steroid Combination in Ocular Trauma (ASCOT) randomised controlled trial is to determine whether adjunctive steroid (triamcinolone acetonide), given at the time of surgery, can improve the outcome of vitreoretinal surgery in patients with open globe ocular trauma. This article presents the statistical analysis plan for the main publication as approved and signed off by the Trial Steering Committee prior to the first data extraction for the Data Monitoring Committee meeting report. ASCOT is a pragmatic, multi-centre, parallel-group, double-masked randomised controlled trial. The aim of the study is to recruit from 20-25 centres in the United Kingdom and randomise 300 eyes (from 300 patients) into two treatment arms. Both groups will receive standard surgical treatment and care; the intervention arm will additionally receive a pre-operative steroid combination (triamcinolone acetonide) into the vitreous cavity consisting of 4 mg/0.1 ml and 40 mg/1 ml sub-Tenon's. Participants will be followed for 6 months post-surgery. The primary outcome is the proportion of patients achieving a clinically meaning improvement in visual acuity in the study eye at 6 months after initial surgery, defined as a 10 letter score improvement in the ETDRS (the standard scale to test visual acuity). ISRCTN30012492 . Registered on 5 September 2014. EudraCT2014-002193-37 . Registered on 5 September 2014.

The effect of bracket ligation on the periodontal status of adolescents undergoing orthodontic treatment. A systematic review and meta-analysis.

PubMed

Arnold, Sina; Koletsi, Despina; Patcas, Raphael; Eliades, Theodore

2016-11-01

This systematic review aimed to critically appraise the evidence regarding the effect of bracket ligation type on the periodontal conditions of adolescents undergoing orthodontic treatment. Search terms included randomized controlled trial (RCTs), controlled clinical trials, ligation, bracket, periodontal, inflammation. Risk of bias assessment was made using the Cochrane risk of bias tool and the quality of evidence was assessed with GRADE. Electronic Database search of published and unpublished literature was performed without language restriction in May 25, 2016 (MEDLINE via Pubmed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Clinical Trials.gov and National Research Register). Of 140 articles initially retrieved, 8 were eligible for inclusion in the systematic review, while 4 RCTs with unclear risk of bias were included in the quantitative synthesis, all comparing self-ligating to conventional steel ligated brackets. Random effects meta-analyses were implemented. At 4-6 weeks after bracket placement there was no evidence to support the use of either type of bracket for achieving improved plaque- (PI) and gingival index (GI). At 3-6 months, there was scarce evidence of greater PI increase for conventional brackets. GI and pocket depth pooled estimates did not reveal significant differences between the two systems. The quality of the evidence was moderate according to GRADE for all outcomes. Overall, non-significant differences on the periodontal status of adolescents undergoing orthodontic treatment with either conventional or self-ligating brackets were detected. The periodontal status of adolescents undergoing orthodontic treatment is of considerable importance. The synthesis of the available evidence on oral hygiene related factors will provide insights to best clinical practice during the course of orthodontic treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nudging and social marketing techniques encourage employees to make healthier food choices: a randomized controlled trial in 30 worksite cafeterias in The Netherlands.

PubMed

Velema, Elizabeth; Vyth, Ellis L; Hoekstra, Trynke; Steenhuis, Ingrid H M

2018-02-01

Currently, many studies focus on how the environment can be changed to encourage healthier eating behavior, referred to as choice architecture or "nudging." However, to date, these strategies are not often investigated in real-life settings, such as worksite cafeterias, or are only done so on a short-term basis. The objective of this study is to examine the effects of a healthy worksite cafeteria ["worksite cafeteria 2.0" (WC 2.0)] intervention on Dutch employees' purchase behavior over a 12-wk period. We conducted a randomized controlled trial in 30 worksite cafeterias. Worksite cafeterias were randomized to either the intervention or control group. The intervention aimed to encourage employees to make healthier food choices during their daily worksite cafeteria visits. The intervention consisted of 14 simultaneously executed strategies based on nudging and social marketing theories, involving product, price, placement, and promotion. Adjusted multilevel models showed significant positive effects of the intervention on purchases for 3 of the 7 studied product groups: healthier sandwiches, healthier cheese as a sandwich filling, and the inclusion of fruit. The increased sales of these healthier meal options were constant throughout the 12-wk intervention period. This study shows that the way worksite cafeterias offer products affects purchase behavior. Situated nudging and social marketing-based strategies are effective in promoting healthier choices and aim to remain effective over time. Some product groups only indicated an upward trend in purchases. Such an intervention could ultimately help prevent and reduce obesity in the Dutch working population. This trial was registered at the Dutch Trial Register (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5372) as NTR5372.

Long-term effects of vitamin D supplementation in vitamin D deficient obese children participating in an integrated weight-loss programme (a double-blind placebo-controlled study) - rationale for the study design.

PubMed

Szlagatys-Sidorkiewicz, Agnieszka; Brzeziński, Michał; Jankowska, Agnieszka; Metelska, Paulina; Słomińska-Frączek, Magdalena; Socha, Piotr

2017-04-04

Obesity is associated not only with an array of metabolic disorders (e.g. insulin resistance, hiperinsulinemia, impaired tolerance of glucose, lipid disorders) but also skeletal and joint abnormalities. Recently, a pleiotropic role of vitamin D has been emphasized. Obese children frequently present with vitamin D deficiency, and greater fat mass is associated with lower serum concentration of this vitamin. Although some evidence suggests that weight loss may affect vitamin D status, this issue has not been studied extensively thus far. The aim of a double-blind placebo-controlled study is to assess long-term health effects of vitamin D supplementation in vitamin D deficient obese children participating in an integrated weight-loss programme. A randomized double-blind, placebo-controlled trial analysing the effects of vitamin D3 supplementation in overweight or obese vitamin D deficient (<30 ng/ml) children participating in an integrated weight-loss programme. Children are randomized to receive either vitamin D (1200 IU) or placebo for 26 weeks. Primary endpoints include changes in BMI (body mass index), body composition and bone mineral density at the end of the study period, and secondary endpoints - the changes in laboratory parameter reflecting liver and kidney function (transaminases, creatinine) and glucose homeostasis (glucose and insulin levels during oral glucose tolerance test). The effects of vitamin D supplementation in obese individuals, especially children, subjected to a weight-loss program are still poorly understood. Considering physiological processes associated with puberty and adolescent growth, we speculate that supplementation may enhance weight reduction and prevent bone loss in obese children deficient in this vitamin. NCT 02828228 ; Trial registration date: 8 Jun 2016; Registered in: ClinicalTrials.gov. The trial was registered retrospectively.

Evaluation of a self-management patient education program for patients with fibromyalgia syndrome: study protocol of a cluster randomized controlled trial.

PubMed

Musekamp, Gunda; Gerlich, Christian; Ehlebracht-König, Inge; Faller, Hermann; Reusch, Andrea

2016-02-03

Fibromyalgia syndrome (FMS) is a complex chronic condition that makes high demands on patients' self-management skills. Thus, patient education is considered an important component of multimodal therapy, although evidence regarding its effectiveness is scarce. The main objective of this study is to assess the effectiveness of an advanced self-management patient education program for patients with FMS as compared to usual care in the context of inpatient rehabilitation. We conducted a multicenter cluster randomized controlled trial in 3 rehabilitation clinics. Clusters are groups of patients with FMS consecutively recruited within one week after admission. Patients of the intervention group receive the advanced multidisciplinary self-management patient education program (considering new knowledge on FMS, with a focus on transfer into everyday life), whereas patients in the control group receive standard patient education programs including information on FMS and coping with pain. A total of 566 patients are assessed at admission, at discharge and after 6 and 12 months, using patient reported questionnaires. Primary outcomes are patients' disease- and treatment-specific knowledge at discharge and self-management skills after 6 months. Secondary outcomes include satisfaction, attitudes and coping competences, health-promoting behavior, psychological distress, health impairment and participation. Treatment effects between groups are evaluated using multilevel regression analysis adjusting for baseline values. The study evaluates the effectiveness of a self-management patient education program for patients with FMS in the context of inpatient rehabilitation in a cluster randomized trial. Study results will show whether self-management patient education is beneficial for this group of patients. German Clinical Trials Register, DRKS00008782 , Registered 8 July 2015.

Propofol versus thiopental sodium for the treatment of refractory status epilepticus.

PubMed

Prabhakar, Hemanshu; Kalaivani, Mani

2015-06-25

This is an updated version of the original Cochrane review published in Issue 8, 2012.Failure to respond to antiepileptic drugs in patients with uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is a substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (26 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 2, February 2015) and MEDLINE (1946 to 26 March 2015). We also searched ClinicalTrials.gov (26 March 2015), the South Asian Database of Controlled Clinical Trials and IndMED (a bibliographic database of Indian Medical Journals). All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol in patients of any age and gender. Two review authors screened the search results and reviewed the abstracts of relevant and eligible trials before retrieving the full-text publications. One study with a total of 24 participants was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE receiving either propofol or thiopental sodium for the control of seizure activity. This study cannot be considered of high methodological quality. This study was terminated early due to recruitment problems. This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. Days of mechanical ventilation were more in patients receiving thiopental sodium when compared with propofol. At three months there was no evidence of a difference between the drugs with respect to outcome measures such as control of seizure activity and functional outcome. Adverse events reported in this study were infection, hypotension and intestinal ischaemia. Since the last version of this review we have found no new studies.There is a lack of robust, randomised, controlled evidence that can clarify the efficacy of propofol and thiopental sodium compared to each other in the treatment of RSE. There is a need for large randomised controlled trials for this serious condition.

[Periodontal treatment for cardiovascular risk factors: a systematic review].

PubMed

Deng, Linkai; Li, Chunjie; Li, Qian; Zhang, Yukui; Zhao, Hongwei

2013-10-01

To evaluate the efficacy of periodontal treatment for the management of cardiovascular risk factors. Eligible studies in Cochrane Controlled Trials Register/CENTRAL, PubMed, EMBASE, and China Biology Medicine disc (CBMdisc) were searched until October 13, 2011. References of the included studies were hand searched. Two reviewers assessed the risk of bias and extracted the data of the included studies in duplicate. Meta-analysis was conducted with Revman 5.1. Six randomized controlled trials involving 682 participants were included. One case had low risk of bias, another one had moderate risk of bias, and the remaining four had high risk of bias. Meta-analysis showed that periodontal treatment has no significant effect on C-reactive protein, total cholesterol, low-density lipoprotein cholesterol, and triglycerides (P > 0.05). However, the treatment had a significant effect on high-density lipoprotein cholesterol [MD = 0.05, 95% CI (0.00, 0.09), P = 0.04]. Periodontal treatment has good effects on controlling high-density lipoprotein cholesterol although more randomized controlled trials must be conducted to verify its effectiveness.

Sildenafil citrate for erectile dysfunction in patients with multiple sclerosis.

PubMed

Xiao, Yousheng; Wang, Jin; Luo, Hongye

2012-04-18

Erectile dysfunction (ED) is a common sexual disease in male patients with multiple sclerosis (MS). Sildenafil citrate is considered as an effective drug in the treatment of male ED in the general population, but it has not been systematically reviewed in patients with MS. To assess the efficacy and safety of sildenafil citrate for ED in patients with MS. We searched the Cochrane (November 2011), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4 of 4, 2011), MEDLINE (PubMed) (January 1966 to November 2011), EMBASE (January 1974 to November 2011) and the China Biological Medicine Database (CBM) (1979 to November 2011). We searched trials registers and conference proceedings and contacted pharmaceutical company and authors of included studies for additional data. There were no language restrictions. Randomised controlled trials comparing sildenafil citrate with placebo or no treatment for ED in patients with MS. Two review authors independently selected articles for inclusion, extracted data and assessed trial quality. Disagreements were resolved by discussion between review authors. Authors of included studies were contacted for additional information. Results were presented as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI). Two randomised controlled trials involving a total of 420 patients were identified. Both trials investigated the short-term efficacy and safety of sildenafil citrate for ED in patients with MS. Patients taking sildenafil citrate were more likely to improve their ability to achieve and maintain an erection measured by International Index of Erectile Function and achieve vaginal penetration ( (RR 1.28, 95%CI 0.92 to 1.78) and complete intercourse measured by Sexual Encounter Profile diary (RR RR 1.38, 95%CI 1.00 to 1.90). and receive A global well respond measured by Global Assessment Question (RR 2.72, 95%CI 1.40 to 5.28) was reported. One trial showed sildenafil citrate is effective in quality of life improvement, while the other trial did not find any significant difference between both groups. Both included trials were judged as high risk of attrition bias. Adverse events were also reported: the most common were headache, flushing, rhinitis, visual disturbances and dyspepsia. Two patients suffered serious adverse events: one with coronary artery disease requiring triple bypass surgery and one with a cerebrovascular accident. There is limited evidence to support sildenafil citrate as an effective treatment for ED in patients with MS. Future well designed randomised, double blinded, placebo-controlled trials with long-term duration are needed.

Characteristics of antimicrobial studies registered in the USA through ClinicalTrials.Gov

PubMed Central

Stockmann, Chris; Sherwin, Catherine M.T.; Ampofo, Krow; Hersh, Adam L.; Pavia, Andrew T.; Byington, Carrie L.; Ward, Robert M.; Spigarelli, Michael G.

2013-01-01

Increasing rates of antimicrobial-resistant infections and the dwindling pipeline of new agents necessitate judicious, evidence-based antimicrobial prescribing. Clinical trials represent a vital resource for establishing evidence of safety and efficacy, which are crucial to guiding antimicrobial treatment decisions. The objective of this study was to comprehensively evaluate the characteristics of antimicrobial research studies registered in ClinicalTrials.gov. Primary outcome measures, funding sources, inclusion criteria and the reporting of study results were evaluated for 16 055 antimicrobial studies registered in ClinicalTrials.gov as of mid 2012. Interventional studies accounted for 93% of registered antimicrobial studies. Clinical trials of drugs (82%) and biologics (9%) were most common. Antibacterial, antiviral and antifungal studies accounted for 43%, 41% and 16% of drug trials, respectively. Among interventional drug trials, 73% featured randomised allocation to study arms and 71% included measures of safety and/or efficacy as primary endpoints. Children were eligible for enrolment in 26% of studies. Among the studies, 60% were sponsored primarily by non-profit organisations, 30% by industry and 10% by the federal government. Only 7% of studies reported results; however, 71% of these were sponsored primarily by industry. Antimicrobial studies commonly incorporated elements of high-quality trial design, including randomisation and safety/efficacy endpoints. Publication of study results and updating of ClinicalTrials.gov should be encouraged for all studies, with particular attention paid to research sponsored by non-profit organisations and governmental agencies. Leveraging the application of these data to guide the careful selection of antimicrobial agents will be essential to preserve their utility for years to come. PMID:23726436

Comparison of noninferiority margins reported in protocols and publications showed incomplete and inconsistent reporting.

PubMed

Dekkers, Olaf M; Cevallos, Myriam; Bührer, Jonas; Poncet, Antoine; Ackermann Rau, Sabine; Perneger, Thomas V; Egger, Matthias

2015-05-01

To compare noninferiority margins defined in study protocols and trial registry records with margins reported in subsequent publications. Comparison of protocols of noninferiority trials submitted 2001 to 2005 to ethics committees in Switzerland and The Netherlands with corresponding publications and registry records. We searched MEDLINE via PubMed, the Cochrane Controlled Trials Register (Cochrane Library issue 01/2012), and Google Scholar in September 2013 to identify published reports, and the International Clinical Trials Registry Platform of the World Health Organization in March 2013 to identify registry records. Two readers recorded the noninferiority margin and other data using a standardized data-abstraction form. The margin was identical in study protocol and publication in 43 (80%) of 54 pairs of study protocols and articles. In the remaining pairs, reporting was inconsistent (five pairs, 9%), or the noninferiority margin was either not reported in the publication (five pairs, 9%) or not defined in the study protocol (one pair). The confidence interval or the exact P-value required to judge whether the result was compatible with noninferior, inferior, or superior efficacy was reported in 43 (80%) publications. Complete and consistent reporting of both noninferiority margin and confidence interval (or exact P-value) was present in 39 (72%) protocol-publication pairs. Twenty-nine trials (54%) were registered in trial registries, but only one registry record included the noninferiority margin. The reporting of noninferiority margins was incomplete and inconsistent with study protocols in a substantial proportion of published trials, and margins were rarely reported in trial registries. Copyright © 2015 Elsevier Inc. All rights reserved.

Early oral switch therapy in low-risk Staphylococcus aureus bloodstream infection (SABATO): study protocol for a randomized controlled trial.

PubMed

Kaasch, Achim J; Fätkenheuer, Gerd; Prinz-Langenohl, Reinhild; Paulus, Ursula; Hellmich, Martin; Weiß, Verena; Jung, Norma; Rieg, Siegbert; Kern, Winfried V; Seifert, Harald

2015-10-09

Current guidelines recommend that patients with Staphylococcus aureus bloodstream infection (SAB) are treated with long courses of intravenous antimicrobial therapy. This serves to avoid SAB-related complications such as relapses, local extension and distant metastatic foci. However, in certain clinical scenarios, the incidence of SAB-related complications is low. Patients with a low-risk for complications may thus benefit from an early switch to oral medication through earlier discharge and fewer complications of intravenous therapy. The major objective for the SABATO trial is to demonstrate that in patients with low-risk SAB a switch from intravenous to oral antimicrobial therapy (oral switch therapy, OST) is non-inferior to a conventional course of intravenous therapy (intravenous standard therapy, IST). The trial is designed as randomized, parallel-group, observer-blinded, clinical non-inferiority trial. The primary endpoint is the occurrence of a SAB-related complication (relapsing SAB, deep-seated infection, and attributable mortality) within 90 days. Secondary endpoints are the length of hospital stay; 14-day, 30-day, and 90-day mortality; and complications of intravenous therapy. Patients with SAB who have received 5 to 7 full days of adequate intravenous antimicrobial therapy are eligible. Main exclusion criteria are polymicrobial bloodstream infection, signs and symptoms of complicated SAB (deep-seated infection, hematogenous dissemination, septic shock, and prolonged bacteremia), the presence of a non-removable foreign body, and severe comorbidity. Patients will receive either OST or IST with a protocol-approved antimicrobial and are followed up for 90 days. Four hundred thirty patients will be randomized 1:1 in two study arms. Efficacy regarding incidence of SAB-related complications is tested sequentially with a non-inferiority margin of 10 and 5 percentage points. The SABATO trial assesses whether early oral switch therapy is safe and effective for patients with low-risk SAB. Regardless of the result, this pragmatic trial will strongly influence the standard of care in SAB. ClinicalTrials.gov NCT01792804 registered 13 February 2013; German Clinical trials register DRKS00004741 registered 4 October 2013, EudraCT 2013-000577-77 . First patient randomized on 20 December 2013.

Pin site care for preventing infections associated with external bone fixators and pins.

PubMed

Lethaby, Anne; Temple, Jenny; Santy-Tomlinson, Julie

2013-12-03

Metal pins are used to apply skeletal traction or external fixation devices in the management of orthopaedic fractures. These percutaneous pins protrude through the skin, and the way in which they are treated after insertion may affect the incidence of pin site infection. This review set out to summarise the evidence of pin site care on infection rates. To assess the effect on infection rates of different methods of cleansing and dressing orthopaedic percutaneous pin sites. In September 2013, for this third update, we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We evaluated all randomised controlled trials (RCTs) that compared the effect on infection and other complication rates of different methods of cleansing or dressing orthopaedic percutaneous pin sites. Two review authors independently assessed the citations retrieved by the search strategies for reports of relevant RCTs, then independently selected trials that satisfied the inclusion criteria, extracted data and undertook quality assessment. A total of eleven trials (572 participants) were eligible for inclusion in the review but not all participants contributed data to each comparison. Three trials compared a cleansing regimen (saline, alcohol, hydrogen peroxide or antibacterial soap) with no cleansing (application of a dry dressing), three trials compared alternative sterile cleansing solutions (saline, alcohol, peroxide, povidone iodine), three trials compared methods of cleansing (one trial compared identical pin site care performed daily or weekly and the two others compared sterile with non sterile techniques), one trial compared daily pin site care with no care and six trials compared different dressings (using different solutions/ointments and dry and impregnated gauze or sponges). One small blinded study of 38 patients found that the risk of pin site infection was significantly reduced with polyhexamethylene biguanide (PHMB) gauze when compared to plain gauze (RR 0.23, 95% CI 0.12 to 0.44) (infection rate of 1% in the PHMB group and 4.5% in the control group) but this study was at high risk of bias as the unit of analysis was observations rather than patients. There were no other statistically significant differences between groups in any of the other trials. The available trial evidence was not extensive, was very heterogeneous and generally of poor quality, so there was insufficient evidence to be able to identify a strategy of pin site care that minimises infection rates. Adequately-powered randomised trials are required to examine the effects of different pin care regimens, and co-interventions - such as antibiotic use - and other extraneous factors must be controlled in the study designs.

Anti-vascular endothelial growth factor for macular oedema secondary to central retinal vein occlusion

PubMed Central

Braithwaite, Tasanee; Nanji, Afshan A; Lindsley, Kristina; Greenberg, Paul B

2014-01-01

Background Central retinal vein occlusion (CRVO) is a relatively common retinal vascular disorder in which macular oedema may develop, with a consequent reduction in visual acuity. Until recently there has been no treatment of proven benefit, but growing evidence supports the use of anti-vascular endothelial growth factor (anti-VEGF) agents. Objectives To investigate the effectiveness and safety of anti-VEGF therapies for the treatment of macular oedema secondary to CRVO. Search methods We searched CENTRAL (which contains the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 10), Ovid MEDLINE (January 1950 to October 2013), EMBASE (January 1980 to October 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2013), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to October 2013), OpenGrey, OpenSIGLE (January 1950 to October 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), Clinical-Trials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and Web of Science Conference Proceedings Citation Index-Science (CPCI-S). There were no language or date restrictions in the electronic search for trials. The electronic databases and clinical trials registers were last searched on 29th October 2013. Selection criteria We considered randomised controlled trials (RCTs) that compared intravitreal anti-VEGF agents of any dose or duration to sham injection or no treatment. We focused on studies that included individuals of any age or gender and a minimum of six months follow-up. Data collection and analysis Two review authors independently assessed trial quality and extracted data. The primary outcome was the proportion of participants with a gain in best-corrected visual acuity (BCVA) from baseline of greater than or equal to 15 letters (3 lines) on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. Secondary outcomes included the proportion of participants with a loss of 15 letters or more of BCVA, the mean change from baseline BCVA, the mean change in central retinal thickness (CRT), the number and type of complications or adverse outcomes, and the number of additional interventions administered. Where available, we also presented quality of life and economic data. Main results We found six RCTs that met the inclusion criteria after independent and duplicate review of the search results. These RCTs included 937 participants and compared outcomes at six months to sham injection for four anti-VEGF agents: aflibercept (VEGF Trap-Eye, Eylea), bevacizumab (Avastin), pegaptanib sodium (Macugen) and ranibizumab (Lucentis). Three trials were conducted in Norway, Sweden and the USA, and three trials were multicentre, one including centres in the USA, Canada, India, Israel, Argentina and Columbia, a second including centres in the USA, Australia, France, Germany, Israel, and Spain, and a third including centres in Austria, France, Germany, Hungary, Italy, Latvia, Australia, Japan, Singapore and South Korea. We performed meta-analysis on three key visual outcomes, using data from up to six trials. High-quality evidence from six trials revealed that participants receiving intravitreal anti-VEGF treatment were 2.71 times more likely to gain at least 15 letters of visual acuity at six months compared to participants treated with sham injections (risk ratio (RR) 2.71; 95% confidence intervals (CI) 2.10 to 3.49). High-quality evidence from five trials suggested anti-VEGF treatment was associated with an 80% lower risk of losing at least 15 letters of visual acuity at six months compared to sham injection (RR 0.20; 95% CI 0.12 to 0.34). Moderate-quality evidence from three trials (481 participants) revealed that the mean reduction from baseline to six months in central retinal thickness was 267.4 μm (95% CI 211.4 μm to 323.4 μm) greater in participants treated with anti-VEGF than in participants treated with sham. The meta-analyses demonstrate that treatment with anti-VEGF is associated with a clinically meaningful gain in vision at six months. One trial demonstrated sustained benefit at 12 months compared to sham. No significant ocular or systemic safety concerns were identified in this time period. Authors’ conclusions Compared to no treatment, repeated intravitreal injection of anti-VEGF agents in eyes with CRVO macular oedema improved visual outcomes at six months. All agents were relatively well tolerated with a low incidence of adverse effects in the short term. Future trials should address the relative efficacy and safety of the anti-VEGF agents and other treatments, including intravitreal corticosteroids, for longer-term outcomes. PMID:24788977

Anti-vascular endothelial growth factor for macular oedema secondary to central retinal vein occlusion.

PubMed

Braithwaite, Tasanee; Nanji, Afshan A; Lindsley, Kristina; Greenberg, Paul B

2014-05-01

Central retinal vein occlusion (CRVO) is a relatively common retinal vascular disorder in which macular oedema may develop, with a consequent reduction in visual acuity. Until recently there has been no treatment of proven benefit, but growing evidence supports the use of anti-vascular endothelial growth factor (anti-VEGF) agents. To investigate the effectiveness and safety of anti-VEGF therapies for the treatment of macular oedema secondary to CRVO. We searched CENTRAL (which contains the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 10), Ovid MEDLINE (January 1950 to October 2013), EMBASE (January 1980 to October 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2013), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to October 2013), OpenGrey, OpenSIGLE (January 1950 to October 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and Web of Science Conference Proceedings Citation Index-Science (CPCI-S). There were no language or date restrictions in the electronic search for trials. The electronic databases and clinical trials registers were last searched on 29th October 2013. We considered randomised controlled trials (RCTs) that compared intravitreal anti-VEGF agents of any dose or duration to sham injection or no treatment. We focused on studies that included individuals of any age or gender and a minimum of six months follow-up. Two review authors independently assessed trial quality and extracted data. The primary outcome was the proportion of participants with a gain in best-corrected visual acuity (BCVA) from baseline of greater than or equal to 15 letters (3 lines) on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. Secondary outcomes included the proportion of participants with a loss of 15 letters or more of BCVA, the mean change from baseline BCVA, the mean change in central retinal thickness (CRT), the number and type of complications or adverse outcomes, and the number of additional interventions administered. Where available, we also presented quality of life and economic data. We found six RCTs that met the inclusion criteria after independent and duplicate review of the search results. These RCTs included 937 participants and compared outcomes at six months to sham injection for four anti-VEGF agents: aflibercept (VEGF Trap-Eye, Eylea), bevacizumab (Avastin), pegaptanib sodium (Macugen) and ranibizumab (Lucentis). Three trials were conducted in Norway, Sweden and the USA, and three trials were multicentre, one including centres in the USA, Canada, India, Israel, Argentina and Columbia, a second including centres in the USA, Australia, France, Germany, Israel, and Spain, and a third including centres in Austria, France, Germany, Hungary, Italy, Latvia, Australia, Japan, Singapore and South Korea. We performed meta-analysis on three key visual outcomes, using data from up to six trials. High-quality evidence from six trials revealed that participants receiving intravitreal anti-VEGF treatment were 2.71 times more likely to gain at least 15 letters of visual acuity at six months compared to participants treated with sham injections (risk ratio (RR) 2.71; 95% confidence intervals (CI) 2.10 to 3.49). High-quality evidence from five trials suggested anti-VEGF treatment was associated with an 80% lower risk of losing at least 15 letters of visual acuity at six months compared to sham injection (RR 0.20; 95% CI 0.12 to 0.34). Moderate-quality evidence from three trials (481 participants) revealed that the mean reduction from baseline to six months in central retinal thickness was 267.4 µm (95% CI 211.4 µm to 323.4 µm) greater in participants treated with anti-VEGF than in participants treated with sham. The meta-analyses demonstrate that treatment with anti-VEGF is associated with a clinically meaningful gain in vision at six months. One trial demonstrated sustained benefit at 12 months compared to sham. No significant ocular or systemic safety concerns were identified in this time period. Compared to no treatment, repeated intravitreal injection of anti-VEGF agents in eyes with CRVO macular oedema improved visual outcomes at six months. All agents were relatively well tolerated with a low incidence of adverse effects in the short term. Future trials should address the relative efficacy and safety of the anti-VEGF agents and other treatments, including intravitreal corticosteroids, for longer-term outcomes.

Benefits and challenges of using the cohort multiple randomised controlled trial design for testing an intervention for depression.

PubMed

Viksveen, Petter; Relton, Clare; Nicholl, Jon

2017-07-06

Trials which test the effectiveness of interventions compared with the status quo frequently encounter challenges. The cohort multiple randomised controlled trial (cmRCT) design is an innovative approach to the design and conduct of pragmatic trials which seeks to address some of these challenges. In this article, we report our experiences with the first completed randomised controlled trial (RCT) using the cmRCT design. This trial-the Depression in South Yorkshire (DEPSY) trial-involved comparison of treatment as usual (TAU) with TAU plus the offer of an intervention for people with self-reported long-term moderate to severe depression. In the trial, we used an existing large population-based cohort: the Yorkshire Health Study. We discuss our experiences with recruitment, attrition, crossover, data analysis, generalisability of results, and cost. The main challenges in using the cmRCT design were the high crossover to the control group and the lower questionnaire response rate among patients who refused the offer of treatment. However, the design did help facilitate efficient and complete recruitment of the trial population as well as analysable data that were generalisable to the population of interest. Attrition rates were also smaller than those reported in other depression trials. This first completed full trial using the cmRCT design testing an intervention for self-reported depression was associated with a number of important benefits. Further research is required to compare the acceptability and cost effectiveness of standard pragmatic RCT design with the cmRCT design. ISRCTN registry: ISRCTN02484593 . Registered on 7 Jan 2013.

Promoting healthful family meals to prevent obesity: HOME Plus, a randomized controlled trial.

PubMed

Fulkerson, Jayne A; Friend, Sarah; Flattum, Colleen; Horning, Melissa; Draxten, Michelle; Neumark-Sztainer, Dianne; Gurvich, Olga; Story, Mary; Garwick, Ann; Kubik, Martha Y

2015-12-15

Family meal frequency has been shown to be strongly associated with better dietary intake; however, associations with weight status have been mixed. Family meals-focused randomized controlled trials with weight outcomes have not been previously conducted. Therefore, this study purpose was to describe weight-related outcomes of the HOME Plus study, the first family meals-focused randomized controlled trial to prevent excess weight gain among youth. Families (n = 160 8-12-year-old children and their parents/guardians) were randomized to intervention (n = 81) or control (n = 79) groups. Data were collected at baseline (2011-2012), post-intervention (12-months post-baseline) and follow-up (21-months post-baseline). The intervention included ten monthly group sessions (nutrition education; hands-on meal and snack planning, preparation, and skill development; screen time reductions) and five motivational, goal-setting phone calls. The main outcome was child body mass index (BMI) z-score. General linear models, adjusted for baseline values and demographics, showed no significant treatment group differences in BMI z-scores at post-intervention or follow-up; however, a promising reduction in excess weight gain was observed. Post-hoc stratification by pubertal onset indicated prepubescent children in the intervention group had significantly lower BMI z-scores than their control group counterparts. The study used a strong theoretical framework, rigorous design, quality measurement and a program with high fidelity to test a family meals-focused obesity prevention intervention. It showed a modest decrease in excess weight gain. The significant intervention effect among prepubescent children suggests the intervention may be more efficacious among relatively young children, although more research with appropriately powered samples are needed to replicate this finding. This study is registered at www.clinicaltrials.gov NCT01538615. Registered 01/17/2012.

Short structured general mental health in service training programme in Kenya improves patient health and social outcomes but not detection of mental health problems - a pragmatic cluster randomised controlled trial

PubMed Central

2013-01-01

Trial design A pragmatic cluster randomised controlled trial. Methods Participants: Clusters were primary health care clinics on the Ministry of Health list. Clients were eligible if they were aged 18 and over. Interventions: Two members of staff from each intervention clinic received the training programme. Clients in both intervention and control clinics subsequently received normal routine care from their health workers. Objective: To examine the impact of a mental health inservice training on routine detection of mental disorder in the clinics and on client outcomes. Outcomes: The primary outcome was the rate of accurate routine clinic detection of mental disorder and the secondary outcome was client recovery over a twelve week follow up period. Randomisation: clinics were randomised to intervention and control groups using a table of random numbers. Blinding: researchers and clients were blind to group assignment. Results Numbers randomised: 49 and 50 clinics were assigned to intervention and control groups respectively. 12 GHQ positive clients per clinic were identified for follow up. Numbers analysed: 468 and 478 clients were followed up for three months in intervention and control groups respectively. Outcome: At twelve weeks after training of the intervention group, the rate of accurate routine clinic detection of mental disorder was greater than 0 in 5% versus 0% of the intervention and control groups respectively, in both the intention to treat analysis (p = 0.50) and the per protocol analysis (p =0.50). Standardised effect sizes for client improvement were 0.34 (95% CI = (0.01,0.68)) for the General Health Questionnaire, 0.39 ((95% CI = (0.22, 0.61)) for the EQ and 0.49 (95% CI = (0.11,0.87)) for WHODAS (using ITT analysis); and 0.43 (95% CI = (0.09,0.76)) for the GHQ, 0.44 (95% CI = (0.22,0.65)) for the EQ and 0.58 (95% CI = (0.18,0.97)) for WHODAS (using per protocol analysis). Harms: None identified. Conclusion The training programme did not result in significantly improved recorded diagnostic rates of mental disorders in the routine clinic consultation register, but did have significant effects on patient outcomes in routine clinical practice. Trial registration International Standard Randomised Controlled Trial Number Register ISRCTN53515024. PMID:24188964

A randomised controlled trial of dietary improvement for adults with major depression (the 'SMILES' trial).

PubMed

Jacka, Felice N; O'Neil, Adrienne; Opie, Rachelle; Itsiopoulos, Catherine; Cotton, Sue; Mohebbi, Mohammedreza; Castle, David; Dash, Sarah; Mihalopoulos, Cathrine; Chatterton, Mary Lou; Brazionis, Laima; Dean, Olivia M; Hodge, Allison M; Berk, Michael

2017-01-30

The possible therapeutic impact of dietary changes on existing mental illness is largely unknown. Using a randomised controlled trial design, we aimed to investigate the efficacy of a dietary improvement program for the treatment of major depressive episodes. 'SMILES' was a 12-week, parallel-group, single blind, randomised controlled trial of an adjunctive dietary intervention in the treatment of moderate to severe depression. The intervention consisted of seven individual nutritional consulting sessions delivered by a clinical dietician. The control condition comprised a social support protocol to the same visit schedule and length. Depression symptomatology was the primary endpoint, assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at 12 weeks. Secondary outcomes included remission and change of symptoms, mood and anxiety. Analyses utilised a likelihood-based mixed-effects model repeated measures (MMRM) approach. The robustness of estimates was investigated through sensitivity analyses. We assessed 166 individuals for eligibility, of whom 67 were enrolled (diet intervention, n = 33; control, n = 34). Of these, 55 were utilising some form of therapy: 21 were using psychotherapy and pharmacotherapy combined; 9 were using exclusively psychotherapy; and 25 were using only pharmacotherapy. There were 31 in the diet support group and 25 in the social support control group who had complete data at 12 weeks. The dietary support group demonstrated significantly greater improvement between baseline and 12 weeks on the MADRS than the social support control group, t(60.7) = 4.38, p < 0.001, Cohen's d = -1.16. Remission, defined as a MADRS score <10, was achieved for 32.3% (n = 10) and 8.0% (n = 2) of the intervention and control groups, respectively (χ 2 (1) = 4.84, p = 0.028); number needed to treat (NNT) based on remission scores was 4.1 (95% CI of NNT 2.3-27.8). A sensitivity analysis, testing departures from the missing at random (MAR) assumption for dropouts, indicated that the impact of the intervention was robust to violations of MAR assumptions. These results indicate that dietary improvement may provide an efficacious and accessible treatment strategy for the management of this highly prevalent mental disorder, the benefits of which could extend to the management of common co-morbidities. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820 . Registered on 29 February 2012.

Enhanced invitation methods to increase uptake of NHS health checks: study protocol for a randomized controlled trial.

PubMed

Forster, Alice S; Burgess, Caroline; McDermott, Lisa; Wright, Alison J; Dodhia, Hiten; Conner, Mark; Miller, Jane; Rudisill, Caroline; Cornelius, Victoria; Gulliford, Martin C

2014-08-30

NHS Health Checks is a new program for primary prevention of heart disease, stroke, diabetes, chronic kidney disease, and vascular dementia in adults aged 40 to 74 years in England. Individuals without existing cardiovascular disease or diabetes are invited for a Health Check every 5 years. Uptake among those invited is lower than anticipated. The project is a three-arm randomized controlled trial to test the hypothesis that enhanced invitation methods, using the Question-Behaviour Effect (QBE), will increase uptake of NHS Health Checks compared with a standard invitation. Participants comprise individuals eligible for an NHS Health Check registered in two London boroughs. Participants are randomized into one of three arms. Group A receives the standard NHS Health Check invitation letter, information sheet, and reminder letter at 12 weeks for nonattenders. Group B receives a QBE questionnaire 1 week before receiving the standard invitation, information sheet, and reminder letter where appropriate. Group C is the same as Group B, but participants are offered a £5 retail voucher if they return the questionnaire. Participants are randomized in equal proportions, stratified by general practice. The primary outcome is uptake of NHS Health Checks 6 months after invitation from electronic health records. We will estimate the incremental health service cost per additional completed Health Check for trial groups B and C versus trial arm A, as well as evaluating the impact of the QBE questionnaire, and questionnaire plus voucher, on the socioeconomic inequality in uptake of Health Checks.The trial includes a nested comparison of two methods for implementing allocation, one implemented manually at general practices and the other implemented automatically through the information systems used to generate invitations for the Health Check. The research will provide evidence on whether asking individuals to complete a preliminary questionnaire, by using the QBE, is effective in increasing uptake of Health Checks and whether an incentive alters questionnaire return rates as well as uptake of Health Checks. The trial interventions can be readily translated into routine service delivery if they are shown to be cost-effective. Current Controlled Trials ISRCTN42856343. Date registered: 21.03.2013.

Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

PubMed

Elphick, Heather E; Southern, Kevin W

2012-06-13

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, their many side effects are well-documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); 2. do not have unacceptable adverse effects.If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.In addition, pharmaceutical companies were approached.Date of the most recent search of the Group's Trials Register: 09 February 2012. Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis. Two trials were identified by the searches; neither was judged eligible for inclusion in the review. No completed randomised controlled trials were included. At present, there are no randomised controlled trials to evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis. Trials with clear outcome measures are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

Despite law, fewer than one in eight completed studies of drugs and biologics are reported on time on ClinicalTrials.gov.

PubMed

Law, Michael R; Kawasumi, Yuko; Morgan, Steven G

2011-12-01

Clinical trial registries are public databases created to prospectively document the methods and measures of prescription drug studies and retrospectively collect a summary of results. In 2007 the US government began requiring that researchers register certain studies and report the results on ClinicalTrials.gov, a public database of federally and privately supported trials conducted in the United States and abroad. We found that although the mandate briefly increased trial registrations, 39 percent of trials were still registered late after the mandate's deadline, and only 12 percent of completed studies reported results within a year, as required by the mandate. This result is important because there is evidence of selective reporting even among registered trials. Furthermore, we found that trials funded by industry were more than three times as likely to report results than were trials funded by the National Institutes of Health. Thus, additional enforcement may be required to ensure disclosure of all trial results, leading to a better understanding of drug safety and efficacy. Congress should also reconsider the three-year delay in reporting results for products that have been approved by the Food and Drug Administration and are in use by patients.

Lymphoma InterVEntion (LIVE) - patient-reported outcome feedback and a web-based self-management intervention for patients with lymphoma: study protocol for a randomised controlled trial.

PubMed

Arts, Lindy P J; van de Poll-Franse, Lonneke V; van den Berg, Sanne W; Prins, Judith B; Husson, Olga; Mols, Floortje; Brands-Nijenhuis, Angelique V M; Tick, Lidwine; Oerlemans, Simone

2017-04-28

Patients with lymphoma are at risk of experiencing adverse physical and psychosocial problems from their cancer and its treatment. Regular screening of these symptoms by the use of patient-reported outcomes (PROs) could increase timely recognition and adequate symptom management. Moreover, self-management interventions intend to enhance knowledge and skills and empower patients to better manage their disease and related problems. The objective of the Lymphoma InterVEntion (LIVE) trial is to examine whether feedback to patients on their PROs and access to a web-based, self-management intervention named Living with lymphoma will increase self-management skills and satisfaction with information, and reduce psychological distress. The LIVE randomised controlled trial consists of three arms: (1) standard care, (2) PRO feedback, and (3) PRO feedback and the Living with lymphoma intervention. Patients who have been diagnosed with Hodgkin lymphoma, non-Hodgkin lymphoma, including chronic lymphocytic leukaemia, as registered in the Netherlands Cancer Registry in various hospitals will be selected for participation. Patients are invited via their haemato-oncologist 6 to 15 months after diagnosis. The PRO feedback includes a graphical overview of patients' own symptom and functioning scores and an option to compare their scores with those of other patients with lymphoma and a normative population of the same age and sex. The Living with lymphoma intervention is based on cognitive behavioural therapy components and includes information, assignments, assessments, and videos. Changes in outcomes from baseline to 16 weeks, 12, and 24 months post intervention will be measured. Primary outcomes are self-management skills, satisfaction with information, and psychological distress. Secondary outcomes are health-related quality of life, illness perceptions, fatigue, and health care use. The results of the LIVE trial will provide novel insights into whether access to PRO feedback and the Living with lymphoma intervention will be effective in increasing self-management skills and satisfaction with information, and reducing distress. The LIVE trial is embedded in a population-based registry, which provides a unique setting to ascertain information on response, uptake, and characteristics of patients with lymphoma in web-based intervention(s). When effective, PRO feedback and Living with lymphoma could serve as easily and widely accessible interventions for coping with lymphoma. Netherlands Trial Register, identifier NTR5953 . Registered on 14 July 2016.

Differences in Investigator-Initiated Trials between Japan and Other Countries: Analyses of Clinical Trials Sponsored by Academia and Government in the ClinicalTrials.gov Registry and in the Three Japanese Registries.

PubMed

Ito, Tatsuya

2016-01-01

Following the amendment of the Pharmaceutical Affairs Law in Japan in 2003 researchers were permitted to begin investigator-initiated trials (IITs). In subsequent years, however, the number of IITs remained low. In other countries in Asia as well as in Europe, North America, and South Africa, the number of IITs has increased over the past decade. The differences in the characteristics of IITs between Japan and other countries are unknown. Some studies have analyzed the characteristics of all clinical trials according to registry databases, but there has been less research focusing on IITs. The purpose of this study is to analyze the characteristics of IITs in the ClinicalTrials.gov registry and in the three Japanese registries, to identify differences in IITs between Japan and other countries. Using Thomson Reuters Pharma™, trials sponsored by academia and government as IITs in 2010 and registered in ClinicalTrials.gov were identified. IITs from 2004 to 2012 in Japan were identified in the three Japanese registries: the University Hospital Medical Information Network Clinical Trials Registry, the Japan Pharmaceutical Information Center Clinical Trials Information, and the Japan Medical Association Center for Clinical Trials, Clinical Trials Registry. Characterization was made of the trial purposes, phases, participants, masking, arms, design, controls, and other data. New and revised IITs registered in ClinicalTrials.gov during 2010 averaged about 40% of all sponsor-identified trials. IITs were nearly all early-phase studies with small numbers of participants. A total of 56 Japanese IITs were found over a period of 8 years, and these were also almost nearly all early-phase studies with small numbers of participants. There appear to be no great differences between Japan and other countries in terms of characteristics of IITs. These results should prompt a new review of the IIT environment in Japan.

Shunting for normal pressure hydrocephalus (NPH).

PubMed

Esmonde, T; Cooke, S

2002-01-01

Since the condition was first described in 1965, the syndrome of normal pressure hydrocephalus (NPH) has conventionally been managed by placement of a cerebrospinal fluid (CSF) shunt. To determine the effectiveness of shunting procedures in promoting stability or improvement in the neurological symptoms and signs of NPH. The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 26 June 2001 using the terms 'shunt*' and 'normal pressure hydrocephalus'. Studies included for analysis were those involving the placement of a CSF shunt for the treatment of NPH as part of a randomized controlled trial. No data matching the selection criteria were found. No randomized controlled trials of shunt placement versus no shunt were found. There is no evidence to indicate whether placement of a shunt is effective in the management of NPH.

Early screening for Chlamydia trachomatis in young women for primary prevention of pelvic inflammatory disease (i-Predict): study protocol for a randomised controlled trial.

PubMed

Tamarelle, Jeanne; Thiébaut, Anne C M; Sabin, Bénédicte; Bébéar, Cécile; Judlin, Philippe; Fauconnier, Arnaud; Rahib, Delphine; Méaude-Roufai, Layidé; Ravel, Jacques; Morré, Servaas A; de Barbeyrac, Bertille; Delarocque-Astagneau, Elisabeth

2017-11-13

Genital infection with Chlamydia trachomatis (Ct) is the most common bacterial sexually transmitted infection, especially among young women. Mostly asymptomatic, it can lead, if untreated, to pelvic inflammatory disease (PID), tubal factor infertility and ectopic pregnancy. Recent data suggest that Ct infections are not controlled in France and in Europe. The effectiveness of a systematic strategy for Ct screening in under-25 women remains controversial. The main objective of the i-Predict trial (Prevention of Diseases Induced by Chlamydia trachomatis) is to determine whether early screening and treatment of 18- to-24-year-old women for genital Ct infection reduces the incidence of PID over 24 months. This is a randomised prevention trial including 4000 eighteen- to twenty-four-year-old sexually active female students enrolled at five universities. The participants will provide a self-collected vaginal swab sample and fill in an electronic questionnaire at baseline and at 6, 12 and 18 months after recruitment. Vaginal swabs in the intervention arm will be analysed immediately for Ct positivity, and participants will be referred for treatment if they have a positive test result. Vaginal swabs from the control arm will be analysed at the end of the study. All visits to general practitioners, gynaecologists or gynaecology emergency departments for pelvic pain or other gynaecological symptoms will be recorded to evaluate the incidence of PID, and all participants will attend a final visit in a hospital gynaecology department. The primary endpoint measure will be the incidence of PID over 24 months. The outcome status (confirmed, probable or no PID) will be assessed by two independent experts blinded to group assignment and Ct status. This trial is expected to largely contribute to the development of recommendations for Ct screening in young women in France to prevent PID and related complications. It is part of a comprehensive approach to gathering data to facilitate decision-making regarding optimal strategies for Ct infection control. The control group of this randomised trial, following current recommendations, will allow better documentation of the natural history of Ct infection, a prerequisite to evaluating the impact of Ct screening. Characterisation of host immunogenetics will also allow identification of women at risk for complications. ClinicalTrials.gov, NCT02904811 . Registered on September 14, 2016. World Health Organisation International Clinical Trials Registry, NCT02904811. AOM, 15-0063 and P150950. Registered on September 26, 2016. A completed Standard Protocol Items : Recommendations for International Trials (SPIRIT) Checklist is available in additional file 1.

Photodynamic therapy for recurrent respiratory papillomatosis.

PubMed

Lieder, Anja; Khan, Muhammad K; Lippert, Burkard M

2014-06-05

Recurrent respiratory papillomatosis (RRP) is a benign condition of the mucosa of the upper aerodigestive tract. It is characterised by recurrent papillomatous lesions and is associated with human papillomavirus (HPV). Frequent recurrence and rapid papilloma growth are common and in part responsible for the onset of potentially life-threatening symptoms. Most patients afflicted by the condition will require repeated surgical treatments to maintain their airway, and these may result in scarring and voice problems. Photodynamic therapy introduces a light-sensitising agent, which is administered either orally or by injection. This substance (called a photo-sensitiser) is selectively retained in hyperplastic and neoplastic tissue, including papilloma. It is then activated by light of a specific wavelength and may be used as a sole or adjuvant treatment for RRP. To assess the effects of photodynamic therapy in the management of recurrent respiratory papillomatosis (RRP) in children and adults. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 27 January 2014. Randomised controlled trials utilising photodynamic therapy as sole or adjuvant therapy in participants of any age with proven RRP versus control intervention. Primary outcome measures were symptom improvement (respiratory distress/dyspnoea and voice quality), quality of life improvement and recurrence-free interval. Secondary outcomes included reduction in the frequency of surgical intervention, reduction in disease volume and adverse effects of treatment.   We used the standard methodological procedures expected by The Cochrane Collaboration. Meta-analysis was not possible and results are presented descriptively. We included one trial with a total of 23 participants. This study was at high risk of bias. None of our primary outcomes and only one of our secondary outcomes (reduction in volume of disease, assessed endoscopically) was measured in the study. There was no significant difference between the groups (very low-quality evidence). Adverse effects reported included airway swelling requiring intubation in a child with severe RRP a few hours after photodynamic therapy. There is insufficient evidence from high-quality randomised controlled trials to determine whether photodynamic therapy alters the course of disease or provides an added benefit to surgery in patients with recurrent respiratory papillomatosis. Multicentre randomised controlled trials with appropriate sample sizes and long-term follow-up are required to evaluate whether photodynamic therapy is of benefit. Outcomes such as improvement in symptoms (respiratory function and voice quality) and quality of life should be measured in future trials.

Home-Based Child Development Interventions for Preschool Children from Socially Disadvantaged Families. Campbell Systematic Reviews. 2012:1

ERIC Educational Resources Information Center

Miller, Sarah; Maguire, Lisa K.; Macdonald, Geraldine

2011-01-01

The purpose of this research is to determine the effects of home-based programmes aimed specifically at improving developmental outcomes for preschool children from socially disadvantaged families. The authors searched the following databases between 7 October and 12 October 2010: Cochrane Central Register of Controlled Trials (CENTRAL) (2010,…

Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations.

PubMed Central

Webster, Lucy; Groskreutz, Derek; Grinbergs-Saull, Anna; Howard, Rob; O'Brien, John T; Mountain, Gail; Banerjee, Sube; Woods, Bob; Perneczky, Robert; Lafortune, Louise; Roberts, Charlotte; McCleery, Jenny; Pickett, James; Bunn, Frances; Challis, David; Charlesworth, Georgina; Featherstone, Katie; Fox, Chris; Goodman, Claire; Jones, Roy; Lamb, Sallie; Moniz-Cook, Esme; Schneider, Justine; Shepperd, Sasha; Surr, Claire; Thompson-Coon, Jo; Ballard, Clive; Brayne, Carol; Burke, Orlaith; Burns, Alistair; Clare, Linda; Garrard, Peter; Kehoe, Patrick; Passmore, Peter; Holmes, Clive; Maidment, Ian; Murtagh, Fliss; Robinson, Louise; Livingston, Gill

2017-01-01

BACKGROUND There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials. OBJECTIVES To agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI). DATA SOURCES We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches. REVIEW METHODS The project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes. RESULTS We included 149 papers from the 22,918 papers screened, referring to 125 individual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally. LIMITATIONS Most of the trials included participants with Alzheimer's disease, so recommendations may not apply to other types of dementia. We did not conduct economic analyses. The PPI consultation was limited to members of the Alzheimer's Society Research Network. CONCLUSIONS Cognitive outcomes and biological markers form the core outcome set for future disease modification trials, measured by the MMSE or ADAS-Cog, and structural MRI in a subset of participants. FUTURE WORK We envisage that the core set may be superseded in the future, particularly for other types of dementia. There is a need to develop an algorithm to compare scores on the MMSE and ADAS-Cog. STUDY REGISTRATION The project was registered with Core Outcome Measures in Effectiveness Trials [ www.comet-initiative.org/studies/details/819?result=true (accessed 7 April 2016)]. The systematic review protocol is registered as PROSPERO CRD42015027346. FUNDING The National Institute for Health Research Health Technology Assessment programme. PMID:28625273

[Cost]effectiveness of withdrawal of fall-risk increasing drugs versus conservative treatment in older fallers: design of a multicenter randomized controlled trial (IMPROveFALL-study)

PubMed Central

2011-01-01

Background Fall incidents represent an increasing public health problem in aging societies worldwide. A major risk factor for falls is the use of fall-risk increasing drugs. The primary aim of the study is to compare the effect of a structured medication assessment including the withdrawal of fall-risk increasing drugs on the number of new falls versus 'care as usual' in older adults presenting at the Emergency Department after a fall. Methods/Design A prospective, multi-center, randomized controlled trial will be conducted in hospitals in the Netherlands. Persons aged ≥65 years who visit the Emergency Department due to a fall are invited to participate in this trial. All patients receive a full geriatric assessment at the research outpatient clinic. Patients are randomized between a structured medication assessment including withdrawal of fall-risk increasing drugs and 'care as usual'. A 3-monthly falls calendar is used for assessing the number of falls, fallers and associated injuries over a one-year follow-up period. Measurements will be at three, six, nine, and twelve months and include functional outcome, healthcare consumption, socio-demographic characteristics, and clinical information. After twelve months a second visit to the research outpatient clinic will be performed, and adherence to the new medication regimen in the intervention group will be measured. The primary outcome will be the incidence of new falls. Secondary outcome measurements are possible health effects of medication withdrawal, health-related quality of life (Short Form-12 and EuroQol-5D), costs, and cost-effectiveness of the intervention. Data will be analyzed using an intention-to-treat analysis. Discussion The successful completion of this trial will provide evidence on the effectiveness of withdrawal of fall-risk increasing drugs in older patients as a method for falls reduction. Trial Registration The trial is registered in the Netherlands Trial Register (NTR1593) PMID:21854643

Use of probiotics to correct dysbiosis of normal microbiota following disease or disruptive events: a systematic review

PubMed Central

McFarland, Lynne V

2014-01-01

Objective To assess the evidence for the claim probiotics can correct dysbiosis of the normal microbiota resulting from disease or disruptive events. Setting Systematic review of published clinical trials of patients receiving a probiotic intervention for the prevention or treatment of various diseases. Data sources Sources searched (1985–2013): PubMed, EMBASE, Cochrane Database of Systematic Reviews, CINAHL, AMED and ISI Web of Science. Three on-line clinical trial registries were searched: Cochrane Central Register of Controlled trials, MetaRegister of Controlled Trials and National Institutes of Health. Review methods Included studies were randomised clinical trials of probiotic interventions having microbiological assays. Studies were evaluated following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for specific probiotic strains. A standard data extraction form was used to collect the raw data. Outcome measures The primary outcome is the degree of microbiota correction by specific probiotic strains. Secondary outcome was the association between the degree of dysbiosis correction and clinical efficacy. Results The review of the literature found three distinct study designs: model A (restoration) assayed patients enrolled with a healthy, undisturbed microbiota and then assayed postdisruptive event and probiotic therapy; model B (alteration) assayed patients with pre-existing disrupted microbiota and then postprobiotic therapy; model C (no dysbiosis) assayed volunteers with no disruptive event prebiotic and postprobiotic. From a total of 63 trials, 83% of the probiotic products using model A restored the microbiota, 56% using model B improved the microbiota and only 21% using model C had any effect on microbiota. Clinical efficacy was more commonly associated with strains capable of restoration of the normal microbiota. Conclusions The ability to assess the degree of dysbiosis improvement is dependent on the enrolled population and the timing of microbiological assays. The functional claim for correcting dysbiosis is poorly supported for most probiotic strains and requires further research. Trial registration number PROSPERO (CRD42014007224). PMID:25157183

Optimal timing of an invasive strategy in patients with non-ST-elevation acute coronary syndrome: a meta-analysis of randomised trials.

PubMed

Jobs, Alexander; Mehta, Shamir R; Montalescot, Gilles; Vicaut, Eric; Van't Hof, Arnoud W J; Badings, Erik A; Neumann, Franz-Josef; Kastrati, Adnan; Sciahbasi, Alessandro; Reuter, Paul-Georges; Lapostolle, Frédéric; Milosevic, Aleksandra; Stankovic, Goran; Milasinovic, Dejan; Vonthein, Reinhard; Desch, Steffen; Thiele, Holger

2017-08-19

A routine invasive strategy is recommended for patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). However, optimal timing of invasive strategy is less clearly defined. Individual clinical trials were underpowered to detect a mortality benefit; we therefore did a meta-analysis to assess the effect of timing on mortality. We identified randomised controlled trials comparing an early versus a delayed invasive strategy in patients presenting with NSTE-ACS by searching MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. We included trials that reported all-cause mortality at least 30 days after in-hospital randomisation and for which the trial investigators agreed to collaborate (ie, providing individual patient data or standardised tabulated data). We pooled hazard ratios (HRs) using random-effects models. This meta-analysis is registered at PROSPERO (CRD42015018988). We included eight trials (n=5324 patients) with a median follow-up of 180 days (IQR 180-360). Overall, there was no significant mortality reduction in the early invasive group compared with the delayed invasive group HR 0·81, 95% CI 0·64-1·03; p=0·0879). In pre-specified analyses of high-risk patients, we found lower mortality with an early invasive strategy in patients with elevated cardiac biomarkers at baseline (HR 0·761, 95% CI 0·581-0·996), diabetes (0·67, 0·45-0·99), a GRACE risk score more than 140 (0·70, 0·52-0·95), and aged 75 years older (0·65, 0·46-0·93), although tests for interaction were inconclusive. An early invasive strategy does not reduce mortality compared with a delayed invasive strategy in all patients with NSTE-ACS. However, an early invasive strategy might reduce mortality in high-risk patients. None. Copyright © 2017 Elsevier Ltd. All rights reserved.

Music in mind, a randomized controlled trial of music therapy for young people with behavioural and emotional problems: study protocol.

PubMed

Porter, Sam; Holmes, Valerie; McLaughlin, Katrina; Lynn, Fiona; Cardwell, Chris; Braiden, Hannah-Jane; Doran, Jackie; Rogan, Sheelagh

2012-10-01

This article is a report of a trial protocol to determine if improvizational music therapy leads to clinically significant improvement in communication and interaction skills for young people experiencing social, emotional or behavioural problems. Music therapy is often considered an effective intervention for young people experiencing social, emotional or behavioural difficulties. However, this assumption lacks empirical evidence. Music in mind is a multi-centred single-blind randomized controlled trial involving 200 young people (aged 8-16 years) and their parents. Eligible participants will have a working diagnosis within the ambit of international classification of disease 10 mental and behavioural disorders and will be recruited over 15 months from six centres within the Child and Adolescent Mental Health Services of a large health and social care trust in Northern Ireland. Participants will be randomly allocated in a 1:1 ratio to receive standard care alone or standard care plus 12 weekly music therapy sessions delivered by the Northern Ireland Music Therapy Trust. Baseline data will be collected from young people and their parents using standardized outcome measures for communicative and interaction skills (primary endpoint), self-esteem, social functioning, depression and family functioning. Follow-up data will be collected 1 and 13 weeks after the final music therapy session. A cost-effectiveness analysis will also be carried out. This study will be the largest trial to date examining the effect of music therapy on young people experiencing social, emotional or behavioural difficulties and will provide empirical evidence for the use of music therapy among this population. Trial registration. This study is registered in the ISRCTN Register, ISRCTN96352204. Ethical approval was gained in October 2010. © 2012 Blackwell Publishing Ltd.

Root resorption during orthodontic treatment.

PubMed

Walker, Sally

2010-01-01

Medline, Embase, LILACS, The Cochrane Library (Cochrane Database of Systematic Reviews, CENTRAL, and Cochrane Oral Health Group Trials Register) Web of Science, EBM Reviews, Computer Retrieval of Information on Scientific Project (CRISP, www.crisp.cit.nih.gov), On-Line Computer Library Center (www.oclc.org), Google Index to Scientific and Technical Proceedings, PAHO (www.paho.org), WHOLis (www.who.int/library/databases/en), BBO (Brazilian Bibliography of Dentistry), CEPS (Chinese Electronic Periodical Services), Conference materials (www.bl.uk/services/bsds/dsc/conference.html), ProQuest Dissertation Abstracts and Thesis database, TrialCentral (www.trialscentral.org), National Research Register (www.controlled-trials.com), www.Clinicaltrials.gov and SIGLE (System for Information on Grey Literature in Europe). Randomised controlled trials including split mouth design, recording the presence or absence of external apical root resorption (EARR) by treatment group at the end of the treatment period. Data were extracted independently by two reviewers using specially designed and piloted forms. Quality was also assessed independently by the same reviewers. After evaluating titles and abstracts, 144 full articles were obtained of which 13 articles, describing 11 trials, fulfilled the criteria for inclusion. Differences in the methodological approaches and reporting results made quantitative statistical comparisons impossible. Evidence suggests that comprehensive orthodontic treatment causes increased incidence and severity of root resorption, and heavy forces might be particularly harmful. Orthodontically induced inflammatory root resorption is unaffected by archwire sequencing, bracket prescription, and self-ligation. Previous trauma and tooth morphology are unlikely causative factors. There is some evidence that a two- to three-month pause in treatment decreases total root resorption. The results were inconclusive in the clinical management of root resorption, but there is evidence to support the use of light forces, especially with incisor intrusion.

Effect of acupuncture and its influence on visceral hypersensitivity in IBS-D patients: Study protocol for a randomized controlled trial.

PubMed

Pei, Lixia; Chen, Hao; Guo, Jing; Chen, Lu; Wu, Xiaoliang; Xu, Wanli; Weng, Shengjie; Yang, EunMee; Hammer, Trine; Sun, Jianhua

2018-05-01

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder associated with visceral hypersensitivity. Increased expression of colonic TRPV1 and decreased expression of microRNA-199 are implicated in the pathogenesis of visceral hypersensitivity in IBS-D patients. Acupuncture is one of the frequently used complementary and alternative therapies for the treatment of IBS. The existing clinical studies mostly use IBS-SSS or other subjective scales, so there is a lack of objective biochemical evidence regarding the effect of acupuncture on IBS. Therefore, we designed this study to investigate whether acupuncture alleviate visceral hypersensitivity by influencing the expression of TRPV1 and microRNA-199. This study is a randomized, sham-controlled trial involving 40 patients and 10 healthy volunteers. A total of 40 eligible patients with IBS-D will be randomly assigned to a traditional acupuncture group or sham acupuncture group in a 1:1 ratio. Patients will receive 3 acupuncture treatment sessions per week for 12 consecutive weeks, for a total of 36 sessions during the study. The primary outcome measure is the IBS-Symptom Severity Score (IBS-SSS). Secondary outcomes are Visceral Pain Scale and levels of TRPV1 and microRNA-199 in colonic tissues. Healthy volunteers will not receive any clinical intervention. The safety of interventions will be assessed at every visit. The purpose of this trial is to evaluate the efficacy of acupuncture for IBS-D through IBS-SSS and Visceral Pain Scale. Furthermore, we want to explore the intervention mechanism of acupuncture in improving visceral hypersensitivity by analyzing the colonic TRPV1 and microRNA-199. This trial is registered with Chinese Clinical Trials Register, ChiCTR-IOR- 17010860(http://www.chictr.org.cn/showproj.aspx?proj=18445).

Registration practices for observational studies on ClinicalTrials.gov indicated low adherence.

PubMed

Boccia, Stefania; Rothman, Kenneth J; Panic, Nikola; Flacco, Maria Elena; Rosso, Annalisa; Pastorino, Roberta; Manzoli, Lamberto; La Vecchia, Carlo; Villari, Paolo; Boffetta, Paolo; Ricciardi, Walter; Ioannidis, John P A

2016-02-01

The study aims to assess the status of registration of observational studies. We identified studies on cancer research with prospective recruitment of participants that were registered from February 2000 to December 2011 in ClinicalTrials.gov. We recorded the dates of registration and start of recruitment, outcomes, and description of statistical method. We searched for publications corresponding to the registered studies through May 31, 2014. One thousand one hundred nine registered studies were eligible. Primary and secondary outcomes were reported in 809 (73.0%) and 464 (41.8%) of them. The date of registration preceded the month of the study start in 145 (13.8%) and coincided in 205 (19.5%). A total of 151 publications from 120 (10.8%) registered studies were identified. In 2 (33.3%) of the 6 publications where ClinicalTrials.gov reported that the study started recruitment after registration, and in 9 (50.0%) of 18 publications where ClinicalTrials.gov reported the same date for registration and start of recruitment, the articles showed that the study had actually started recruiting before registration. During the period reviewed, few observational studies have been registered. Registration usually occurred after the study started, and prespecification of outcomes and statistical analysis rarely occurred. Copyright © 2016 Elsevier Inc. All rights reserved.

Amnioinfusion for preterm rupture of membranes.

PubMed

Hofmeyr, G J

2000-01-01

Preterm rupture of membranes places a fetus at risk of cord compression and amnionitis. Amnioinfusion aims to prevent or relieve umbilical cord compression by infusing a solution into the uterine cavity. The objective of this review was to assess the effects of amnioinfusion for preterm rupture of membranes on maternal and perinatal outcomes. The Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register were searched. Randomised trials of amnioinfusion compared to no amnioinfusion in women with preterm rupture of membranes. Eligibility and trial quality were assessed by the reviewer. One trial of 66 women was included. It had some methodological flaws. No significant differences between amnioinfusion and no amnioinfusion were detected for caesarean section (relative risk 0.32, 95% confidence interval 0.07 to 1.40); low Apgar scores (relative risk 0.28, 95% confidence interval 0.03 to 2.33) or neonatal death (relative risk 0.55, 95% confidence interval 0.05 to 5.77). In the amnioinfusion group, the number of severe fetal heart rate decelerations per hour during the first stage of labour were reduced (weighted mean difference -1.20, 95% confidence interval -1.83 to -0.57). These outcomes are consistent with those found in the Cochrane review on amnioinfusion for cord compression. There is not enough evidence concerning the use of amnioinfusion for preterm rupture of membranes.

A 3-Arm randomised controlled trial of Communicating Healthy Beginnings Advice by Telephone (CHAT) to mothers with infants to prevent childhood obesity.

PubMed

Wen, Li Ming; Rissel, Chris; Baur, Louise A; Hayes, Alison J; Xu, Huilan; Whelan, Anna; Hua, Myna; Shaw, Miranda; Phongsavan, Philayrath

2017-01-14

With an increasing prevalence of obesity in young children globally, there is an urgent need for the development of effective early interventions. A previous Healthy Beginnings Trial using a nurse-led home visiting program has demonstrated that providing mothers with evidence-based advice can improve maternal practice regarding obesity prevention, and can reduce Body Mass Index (BMI) in the first few years of life. However, the costs for scale-up of home visiting limit its population reach. This trial aims to determine the efficacy of Communicating Healthy Beginnings Advice by Telephone (CHAT) to mothers with infants in improving infant feeding practices and preventing the early onset of childhood overweight and obesity. We propose a 3-arm randomised controlled trial (RCT) with a consecutive sample of 1056 mothers with their newborn children in New South Wales (NSW) Australia. Pregnant women who are between weeks 28 and 34 of their pregnancy will be invited to participate in the CHAT trial. Informed consent will be obtained, and after baseline data collection, participants will be randomly allocated to the telephone intervention, text messaging intervention, or the control group. The intervention comprises telephone consultations or text messages, together with 6 intervention packages being mailed at specific times from the third trimester of pregnancy until 12 months post birth. The main trial outcome measures include a) duration of breastfeeding, b) timing of introduction of solids, c) nutrition behaviours, physical activity and television viewing, and d) weight and BMI z-score at 12 and 24 months, e) cost-effectiveness, as well as f) feasibility and acceptability of the interventions. The results will ascertain whether early intervention using telephone consultation or text messaging together with staged mailed intervention resources can be feasible and effective in improving infant feeding practices, physical activity and reducing children's BMI in the early years of life. If proven to be feasible, effective as well as cost-effective, the trial results will inform a series of recommendations for policy and practice related to promoting healthy infant feeding and physical activity in young children in the first years of life. The CHAT Trial is registered with the Australian Clinical Trial Registry ( ACTRN12616001470482p ). It was registered on October 21, 2016.

Haemodilution for acute ischaemic stroke

PubMed Central

Chang, Timothy S; Jensen, Matthew B

2014-01-01

Background Ischaemic stroke interrupts the flow of blood to part of the brain. Haemodilution is thought to improve the flow of blood to the affected areas of the brain and thus reduce infarct size. Objectives To assess the effects of haemodilution in acute ischaemic stroke. Search methods We searched the Cochrane Stroke Group Trials Register (February 2014), the Cochrane Central Register of Controlled Trials (Issue 1, 2014), MEDLINE (January 2008 to October 2013) and EMBASE (January 2008 to October 2013). We also searched trials registers, scanned reference lists and contacted authors. For the previous version of the review, the authors contacted manufacturers and investigators in the field. Selection criteria Randomised trials of haemodilution treatment in people with acute ischaemic stroke. We included only trials in which treatment was started within 72 hours of stroke onset. Data collection and analysis Two review authors assessed trial quality and one review author extracted the data. Main results We included 21 trials involving 4174 participants. Nine trials used a combination of venesection and plasma volume expander. Twelve trials used plasma volume expander alone. The plasma volume expander was plasma alone in one trial, dextran 40 in 12 trials, hydroxyethyl starch (HES) in five trials and albumin in three trials. Two trials tested haemodilution in combination with another therapy. Evaluation was blinded in 14 trials. Five trials probably included some participants with intracerebral haemorrhage. Haemodilution did not significantly reduce deaths within the first four weeks (risk ratio (RR) 1.10; 95% confidence interval (CI) 0.90 to 1.34). Similarly, haemodilution did not influence deaths within three to six months (RR 1.05; 95% CI 0.93 to 1.20), or death and dependency or institutionalisation (RR 0.96; 95% CI 0.85 to 1.07). The results were similar in confounded and unconfounded trials, and in trials of isovolaemic and hypervolaemic haemodilution. No statistically significant benefits were documented for any particular type of haemodiluting agents, but the statistical power to detect effects of HES was weak. Six trials reported venous thromboembolic events. There was a tendency towards reduction in deep venous thrombosis or pulmonary embolism or both at three to six months’ follow-up (RR 0.68; 95% CI 0.37 to 1.24). There was no statistically significant increased risk of serious cardiac events among haemodiluted participants. Authors’ conclusions The overall results of this review showed no clear evidence of benefit of haemodilution therapy for acute ischaemic stroke. These results are compatible with no persuasive beneficial evidence of haemodilution therapy for acute ischaemic stroke. This therapy has not been proven to improve survival or functional outcome. PMID:25159027

Can a documentary increase help-seeking intentions in men? A randomised controlled trial

PubMed Central

Schlichthorst, Marisa; Spittal, Matthew J; Phelps, Andrea; Pirkis, Jane

2018-01-01

Background We investigated whether a public health intervention—a three-part documentary called Man Up which explored the relationship between masculinity and mental health, well-being and suicidality—could increase men’s intentions to seek help for personal and emotional problems. Methods We recruited men aged 18 years or over who were not at risk of suicide to participate in a double-blind randomised controlled trial. Participants were randomly assigned (1:1) via computer randomisation to view Man Up (the intervention) or a control documentary. We hypothesised that 4 weeks after viewing Man Up participants would report higher levels of intention to seek help than those who viewed the control documentary. Our primary outcome was assessed using the General Help Seeking Questionnaire, and was analysed for all participants. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616001169437, Universal Trial Number: U1111-1186-1459) and was funded by the Movember Foundation. Results Three hundred and fifty-four men were assessed for eligibility for the trial and randomised to view Man Up or the control documentary. Of these, 337 completed all stages (nine participants were lost to follow-up in the intervention group and eight in the control group). Linear regression analysis showed a significant increase in intentions to seek help in the intervention group, but not in the control group (coef.=2.06, 95% CI 0.48 to 3.63, P=0.01). Conclusions Our trial demonstrates the potential for men’s health outcomes to be positively impacted by novel, media-based public health interventions that focus on traditional masculinity. Trial registration number ACTRN12616001169437, Results. PMID:29101215

Chlorambucil for patients with primary biliary cirrhosis.

PubMed

Li, Wei Xin; Yan, Xiang; Shi, Chun Rui; Zhang, Ai Ping

2012-09-12

Chlorambucil has been used for patients with primary biliary cirrhosis as it possesses immunosuppressive properties. But it is unknown whether it benefits or harms these patients. To evaluate the beneficial and any harmful effects of chlorambucil for primary biliary cirrhosis patients. Eligible trials were identified by searching the Cochrane Hepato-Biliary Group Controlled Trials Register (March 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2012, Issue 2), MEDLINE (1946 to March 2012), EMBASE (1974 to March 2012), Science Citation Index EXPANDED (1900 to March 2012), The Chinese Biomedical Database (1976 to March 2012), The Chinese Medical Current Contents (1994 to March 2012), The China Hospital Knowledge Database (1994 to March 2012), and a database of ongoing trials (http://www.controlled-trials.com/mrct/) (accessed 6 March 2012). The reference lists of the retrieved publications and review articles were also read through, and pharmaceutical companies known to produce chlorambucil were contacted. Randomised clinical trials, irrespective of language, year of publication, and publication status, comparing chlorambucil at any dose versus placebo, no intervention, another active drug, or one dose of chlorambucil with another dose. We planned to assess continuous data with mean differences (MD), and dichotomous outcomes with relative risk (RR), both with 95% confidence intervals (CI). As we only identified one trial, Fisher's exact tests were employed. Only one randomised trial was identified and included in the review. The bias risk in the trial was high. The trial compared chlorambucil versus no intervention in 24 patients with primary biliary cirrhosis. Fisher's exact test did not show a significant reduction of mortality when comparing chlorambucil with no treatment (0/13 (0%) versus (2/11 (18.2%); P = 0.20). There was no significant difference regarding adverse events for chlorambucil compared with no treatment, but all patients receiving chlorambucil experienced adverse events (13/13 (100%) versus (3/11 (27%); P = 0.1). According to the authors of the trial, chlorambucil led to a significant improvement in mean serum levels of bilirubin (P < 0.05), albumin (P < 0.05), immunoglobulin M (P < 0.01), serum aspartate aminotransferase activity (P < 0.01), and hepatic inflammatory infiltrates (P < 0.01). There is not sufficient evidence to support or reject the use of chlorambucil for patients with primary biliary cirrhosis. Chlorambucil may show benefit in some unvalidated surrogate outcome measures (for example, serum bilirubin and immunoglobulin M levels). Chlorambucil is, however, connected with a number of adverse events. Bone marrow suppression should be noted in particular. Further randomised clinical trials are necessary to assess the benefits and harms of chlorambucil in this indication.

Methods to improve recruitment to randomised controlled trials: Cochrane systematic review and meta-analysis

PubMed Central

Treweek, Shaun; Lockhart, Pauline; Pitkethly, Marie; Cook, Jonathan A; Kjeldstrøm, Monica; Johansen, Marit; Taskila, Taina K; Sullivan, Frank M; Wilson, Sue; Jackson, Catherine; Jones, Ritu; Mitchell, Elizabeth D

2013-01-01

This review is an abridged version of a Cochrane Review previously published in the Cochrane Database of Systematic Reviews 2010, Issue 4, Art. No.: MR000013 DOI: 10.1002/14651858.MR000013.pub5 (see www.thecochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and Cochrane Database of Systematic Reviews should be consulted for the most recent version of the review. Objective To identify interventions designed to improve recruitment to randomised controlled trials, and to quantify their effect on trial participation. Design Systematic review. Data sources The Cochrane Methodology Review Group Specialised Register in the Cochrane Library, MEDLINE, EMBASE, ERIC, Science Citation Index, Social Sciences Citation Index, C2-SPECTR, the National Research Register and PubMed. Most searches were undertaken up to 2010; no language restrictions were applied. Study selection Randomised and quasi-randomised controlled trials, including those recruiting to hypothetical studies. Studies on retention strategies, examining ways to increase questionnaire response or evaluating the use of incentives for clinicians were excluded. The study population included any potential trial participant (eg, patient, clinician and member of the public), or individual or group of individuals responsible for trial recruitment (eg, clinicians, researchers and recruitment sites). Two authors independently screened identified studies for eligibility. Results 45 trials with over 43 000 participants were included. Some interventions were effective in increasing recruitment: telephone reminders to non-respondents (risk ratio (RR) 1.66, 95% CI 1.03 to 2.46; two studies, 1058 participants), use of opt-out rather than opt-in procedures for contacting potential participants (RR 1.39, 95% CI 1.06 to 1.84; one study, 152 participants) and open designs where participants know which treatment they are receiving in the trial (RR 1.22, 95% CI 1.09 to 1.36; two studies, 4833 participants). However, the effect of many other strategies is less clear, including the use of video to provide trial information and interventions aimed at recruiters. Conclusions There are promising strategies for increasing recruitment to trials, but some methods, such as open-trial designs and opt-out strategies, must be considered carefully as their use may also present methodological or ethical challenges. Questions remain as to the applicability of results originating from hypothetical trials, including those relating to the use of monetary incentives, and there is a clear knowledge gap with regard to effective strategies aimed at recruiters. PMID:23396504

Urate oxidase for the prevention and treatment of tumour lysis syndrome in children with cancer.

PubMed

Cheuk, Daniel K L; Chiang, Alan K S; Chan, Godfrey C F; Ha, Shau Yin

2014-08-14

Tumour lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Preliminary reports suggest that urate oxidase is effective in reducing serum uric acid, the build-up of which causes TLS. It is uncertain whether high-quality evidence exists to support its routine use in children with malignancies. To assess the effects and safety of urate oxidase for the prevention and treatment of TLS in children with malignancies. This is an update of the original review. We performed a comprehensive search of the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library issue 1, 2013), MEDLINE (1966 to February 2013), Embase (1980 to February 2013), and CINAHL (1982 to February 2013). In addition, we searched the reference lists of all identified relevant papers. We also explored other internet sources (updated search on 26 February 2013): the NHS' National Research Register, the US National Institutes of Health Ongoing Trials Register, the metaRegister of Controlled Trials, and ProQuest Dissertations & Theses Database. We also screened conference proceedings of the American Society of Clinical Oncology, the European Society for Medical Oncology, and the International Society of Paediatric Oncology meetings from 1993 to 2012. Finally, we contacted experts in the field and the manufacturer of rasburicase, Sanofi-aventis. Randomised controlled trials (RCT) and controlled clinical trials (CCT) of urate oxidase for the prevention or treatment of TLS in children under 18 years with any malignancy. Two review authors independently extracted trial data and assessed individual trial quality. We used risk ratios (RR) for dichotomous data and mean difference (MD) for continuous data. We included seven trials, involving 471 participants in the treatment groups and 603 participants in the control groups. One RCT and five CCTs compared urate oxidase and allopurinol. Three trials tested Uricozyme, and three trials tested rasburicase for the prevention of TLS.The RCT showed no significant difference in mortality (both all-cause mortality and mortality due to TLS), renal failure, and adverse effects between the treatment and the control groups. The frequency of normalisation of uric acid at four hours (Fisher's exact test P < 0.001) and area under curve of uric acid at four days (MD -201.00 mg/dLhr, 95% confidence interval (CI) -258.05 mg/dLhr to -143.95 mg/dLhr; P < 0.00001) were significantly better in the treatment group. The trial did not evaluate the primary outcome (incidence of clinical TLS).Pooled results of three CCTs showed significantly lower mortality due to TLS in the treatment group (RR 0.05, 95% CI 0.00 to 0.89; P = 0.04); all-cause mortality was not significantly different between the groups. Pooled results from five CCTs showed significantly lower incidence of renal failure in the treatment group (RR 0.26, 95% CI 0.08 to 0.89; P = 0.03). Results of CCTs also showed significantly lower uric acid in the treatment group at two days (three CCTs), three days (two CCTs), four days (two CCTs), and seven days (one CCT) after therapy, but not one day (three CCTs), five days (one CCT), and 12 days (one CCT) after therapy. Pooled results from three CCTs showed higher frequency of adverse effects in participants who received urate oxidase (RR 9.10, 95% CI 1.29 to 64.00; P = 0.03). One CCT evaluated the primary outcome; no significant difference was identified.Another included RCT, with 30 participants, compared different doses of rasburicase (0.2 mg/kg versus 0.15 mg/kg), which demonstrated no significant difference in uric acid normalisation and uric acid level at four hours). Common adverse events of urate oxidase included hypersensitivity, haemolysis, and anaemia, but no significant difference between treatment groups was identified. No significant difference in mortality (all-cause mortality and mortality due to TLS) and renal failure was identified. The primary outcome was not evaluated.All included trials were highly susceptible to biases. Although urate oxidase might be effective in reducing serum uric acid, it is unclear whether it reduces clinical tumour lysis syndrome, renal failure, or mortality. Adverse effects might be more common for urate oxidase compared with allopurinol. Clinicians should weigh the potential benefits of reducing uric acid and uncertain benefits of preventing mortality or renal failure from TLS against the potential risk of adverse effects.

Using routinely recorded data in the UK to assess outcomes in a randomised controlled trial: The Trials of Access.

PubMed

Powell, G A; Bonnett, L J; Tudur-Smith, C; Hughes, D A; Williamson, P R; Marson, A G

2017-08-23

In the UK, routinely recorded data may benefit prospective studies including randomised controlled trials (RCTs). In an on-going study, we aim to assess the feasibility of access and agreement of routinely recorded clinical and non-clinical data compared to data collected during a RCT using standard prospective methods. This paper will summarise available UK routinely recorded data sources and discuss our experience with the feasibility of accessing routinely recorded data for participants of a RCT before finally proposing recommendations for improving the access and implementation of routinely recorded data in RCTs. Setting: the case study RCT is the Standard and New Antiepileptic Drugs II (SANAD II) trial, a pragmatic, UK, multicentre, phase IV RCT assessing the clinical and cost-effectiveness of antiepileptic drug treatments for newly diagnosed epilepsy. 98 participants have provided written consent to permit the request of routinely recorded data. Study procedures: routinely recorded clinical and non-clinical data were identified and data requested through formal applications from available data holders for the duration that participants have been recruited into SANAD II. The feasibility of accessing routinely recorded data during a RCT is assessed and recommendations for improving access proposed. Secondary-care clinical and socioeconomic data is recorded on a national basis and can be accessed, although there are limitations in the application process. Primary-care data are recorded by a number of organisations on a de-identified basis but access for specific individuals has not been feasible. Access to data recorded by non-clinical sources, including The Department for Work and Pensions and The Driving and Vehicle Licensing Agency, was not successful. Recommendations discussed include further research to assess the attributes of routinely recorded data, an assessment of public perceptions and the development of strategies to collaboratively improve access to routinely recorded data for research. International Standard Randomised Controlled Trials, ISRCTN30294119 . Registered on 3 July 2012. EudraCT No: 2012-001884-64. Registered on 9 May 2012.

Effect of Pycnogenol® on attention-deficit hyperactivity disorder (ADHD): study protocol for a randomised controlled trial.

PubMed

Verlaet, Annelies A J; Ceulemans, Berten; Verhelst, Helene; Van West, Dirk; De Bruyne, Tess; Pieters, Luc; Savelkoul, Huub F J; Hermans, Nina

2017-03-28

Methylphenidate (MPH), the first choice medication for attention-deficit hyperactivity disorder (ADHD), is associated with serious adverse effects like arrhythmia. Evidence on the association of ADHD with immune and oxidant-antioxidant imbalances offers potential for antioxidant and/or immunomodulatory nutritional supplements as ADHD therapy. One small randomised trial in ADHD suggests, despite various limitations, therapeutic benefit from Pycnogenol®, a herbal, polyphenol-rich extract. This phase III trial is a 10-week, randomised, double-blind, placebo and active treatment controlled multicentre trial with three parallel treatment arms to compare the effect of Pycnogenol® to MPH and placebo on the behaviour of 144 paediatric ADHD and attention-deficit disorder (ADD) patients. Evaluations of behaviour (measured by the ADHD-Rating Scale (primary endpoint) and the Social-emotional Questionnaire (SEQ)), immunity (plasma cytokine and antibody levels, white blood cell counts and faecal microbial composition), oxidative stress (erythrocyte glutathione, plasma lipid-soluble vitamins and malondialdehyde and urinary 8-OHdG levels, as well as antioxidant enzyme activity and gene expression), serum zinc and neuropeptide Y level, urinary catecholamines and physical complaints (Physical Complaints Questionnaire) will be performed in week 10 and compared to baseline. Acceptability evaluations will be based on adherence, dropouts and reports of adverse events. Dietary habits will be taken into account. This trial takes into account comorbid behavioural and physical symptoms, as well as a broad range of innovative immune and oxidative biomarkers, expected to provide fundamental knowledge on ADHD aetiology and therapy. Research on microbiota in ADHD is novel. Moreover, the active control arm is rather unseen in research on nutritional supplements, but of great importance, as patients and parents are often concerned with the side effects of MPH. Clinicaltrials.gov number: NCT02700685 . Registered on 18 January 2016. EudraCT 2016-000215-32 . Registered on 4 October 2016.

Should in-line filters be used in peripheral intravenous catheters to prevent infusion-related phlebitis? A systematic review of randomized controlled trials.

PubMed

Niël-Weise, Barbara S; Stijnen, Theo; van den Broek, Peterhans J

2010-06-01

In this systematic review, we assessed the effect of in-line filters on infusion-related phlebitis associated with peripheral IV catheters. The study was designed as a systematic review and meta-analysis of randomized controlled trials. We used MEDLINE and the Cochrane Controlled Trial Register up to August 10, 2009. Two reviewers independently assessed trial quality and extracted data. Data on phlebitis were combined when appropriate, using a random-effects model. The impact of the risk of phlebitis in the control group (baseline risk) on the effect of in-line filters was studied by using meta-regression based on the bivariate meta-analysis model. The quality of the evidence was determined by using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) method. Eleven trials (1633 peripheral catheters) were included in this review to compare the effect of in-line filters on the incidence of phlebitis in hospitalized patients. Baseline risks across trials ranged from 23% to 96%. Meta-analysis of all trials showed that in-line filters reduced the risk of infusion-related phlebitis (relative risk, 0.66; 95% confidence interval, 0.43-1.00). This benefit, however, is very uncertain, because the trials had serious methodological shortcomings and meta-analysis revealed marked unexplained statistical heterogeneity (P < 0.0000, I(2) = 90.4%). The estimated benefit did not depend on baseline risk. In-line filters in peripheral IV catheters cannot be recommended routinely, because evidence of their benefit is uncertain.

Cephalic version by moxibustion for breech presentation.

PubMed

Coyle, M E; Smith, C A; Peat, B

2005-04-18

Moxibustion (a type of Chinese medicine which involves burning a herb close to the skin) to the acupuncture point Bladder 67 (BL67) (Chinese name Zhiyin), located at the tip of the fifth toe, has been proposed as a way of correcting breech presentation. As caesarean section is often suggested for breech babies due to the potential difficulties during labour, it is preferable to turn the baby before labour starts. To examine the effectiveness and safety of moxibustion on changing the presentation of an unborn baby in the breech position, the need for external cephalic version (ECV), mode of birth, and perinatal morbidity and mortality for breech presentation. We searched the Cochrane Pregnancy and Childbirth Group trials register (30 August 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2004), MEDLINE (1966 to March 2004), EMBASE (1980 to March 2004), CINAHL (1982 to March 2004), MIDIRS (1982 to March 2004), CISCOM (9 March 2004) and bibliographies of relevant papers. The inclusion criteria were published and unpublished randomised controlled trials comparing moxibustion (either alone or in combination with acupuncture) with a control group (no moxibustion), or other methods (e.g. external cephalic version, acupuncture) in women with a singleton breech presentation. Both authors assessed eligibility and quality of trials independently. The outcome measures were baby's presentation at birth, need for external cephalic version, mode of birth, perinatal morbidity and mortality, maternal complications and maternal satisfaction, and adverse events. Three trials involving a total of 597 women were included. Due to differences in interventions and sample size it was not appropriate to perform a meta-analysis for the main outcome. Only one trial reported on other outcome measures relevant to this review. Moxibustion reduced the need for ECV (relative risk (RR) 0.47, 95% confidence interval (CI) 0.33 to 0.66) and resulted in decreased use of oxytocin before or during labour for women who had vaginal deliveries (RR 0.28, 95% CI 0.13 to 0.60). There is insufficient evidence to support the use of moxibustion to correct a breech presentation. Moxibustion may be beneficial in reducing the need for ECV, and decreasing the use of ocytocin, however there is a need for well-designed randomised controlled trials to evaluate moxibustion for breech presentation which report on clinically relevant outcomes as well as the safety of the intervention.

Overview of registered studies in orthodontics: Evaluation of the ClinicalTrials.gov registry.

PubMed

Allareddy, Veerasathpurush; Rampa, Sankeerth; Masoud, Mohamed I; Lee, Min Kyeong; Nalliah, Romesh; Allareddy, Veerajalandhar

2014-11-01

The Food and Drug Administration Modernization Act of 1997 made it mandatory for all phase II through IV trials regulated by this Act to be registered. After this, the National Institutes of Health created ClinicalTrials.gov, which is a registry of publicly and privately supported clinical studies of human participants. The objective of this study was to examine the characteristics of registered studies in orthodontics. The ClinicalTrials.gov Web site was used to query all registered orthodontic studies. The search term used was "orthodontics." No limitations were placed for the time period. All registered studies regardless of their recruitment status, study results, and study type were selected for analysis. A total of 64 orthodontic studies were registered as of January 1, 2014. Of these, 52 were interventional, and 12 were observational. Close to 60% of the interventional studies and 66.7% of the observational studies had sample sizes of 50 or fewer subjects. About 21.2% of the interventional studies and 16.7% of the observational studies had sample sizes greater than 100. Only 1 study was funded by the National Institutes of Health, and the rest were funded by "other" or "industry" sources. Close to 87.7% of the interventional studies were randomized. Interventional model assignments included factorial assignment (3.9%), parallel assignments (74.5%), crossover assignment (7.8%), and single-group assignment (13.7%). Most studies were treatment oriented (80.4%). The types of masking used by the interventional studies included open label (28.9%), single blind (44.2%), and double blind (26.9%). Outcome assessors were blinded in only 6 studies. Orthodontic studies registered in ClinicalTrials.gov are dominated by small single-center studies. There are wide variations with regard to treatment allocation approaches and randomization methods in the studies. These results also indicate the need for multicenter clinical studies in orthodontics. Copyright © 2014 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Photodynamic therapy for chronic periodontitis.

PubMed

Herrera, David

2011-01-01

Medline, Embase, The Cochrane Oral Health Group's Trials Register, CENTRAL, UK National Research Register, ISI Proceedings, hand search of relevant journals for 2000-2008. References from selected articles and contact with authors. Randomised controlled trials in any language comparing scaling and root planing (SRP) alone and SRP with PDT in patients with chronic periodontitis, with a mean follow up of at least 12 weeks. The primary outcome measure was the change in clinical attachment loss (CAL). Secondary outcomes were changes in probing depth (PD) and gingival recession (GR). Data were extracted by a single reviewer using a standard extraction form. Quality was assessed using both the Jadad scale and the allocation concealment component of the Cochrane risk of bias tool. Meta-analysis was conducted using the random effects model. Heterogeneity was assessed using the chi-squared-based Q statistic method and Higgins' I(2) test. Four trials with 101 participants were included. The risk of bias of these trials was considered to be moderate. The mean difference in CAL at 12 weeks was 0.29 mm (95% CI 0.08-0.50, p=0.007). Heterogeneity was high using both the Chi(2) and I(2) tests. The review suggests there may be a minor improvement in clinical attachment loss at 12 weeks. It is unclear whether this is a clinically meaningful improvement.

Chinese Herbal Medicine for Postpartum Depression: A Systematic Review of Randomized Controlled Trials

PubMed Central

Li, Yongle; Chen, Zijie; Yu, Ning; Yao, Keyu; Che, Yiwen; Xi, Yupeng

2016-01-01

Background. Postpartum depression (PPD) does great harm to women following childbirth. The aim of this study was to conduct a systematic review of the literature to assess the efficacy and safety of CHM for the treatment of PPD. Methods. Published or ongoing registered trials were searched for from the inception of the various databases to December 31, 2015. Data extraction and methodology assessment were conducted independently by two researchers. RevMan 5.3 software was used to analyze the data. Results. Forty-seven registered clinical trials (RCTs) were identified and reviewed. The results showed CHM alone or in combination with routine treatments could reduce HAMD score, EPDS score, incidence of adverse events, TESS, and SERS. CHM combined with routine treatment was more effective in increasing serum estradiol levels and reducing progesterone levels than routine treatment alone. Meanwhile, pooled data revealed that MRLQS combined with routine treatments or MRLQS plus MSHS combined with routine treatments were more effective than other therapeutic methods in TCM. MRLQS plus MSHS alone was found to be an effective alternative when compared to routine treatments. Conclusions. This review suggested that CHM was safe and effective in the treatment of PPD. However, this could not be proven conclusively. To ensure evidence-based clinical practice, more rigorously designed trials are warranted. PMID:27774110

UK publicly funded Clinical Trials Units supported a controlled access approach to share individual participant data but highlighted concerns

PubMed Central

Hopkins, Carolyn; Sydes, Matthew; Murray, Gordon; Woolfall, Kerry; Clarke, Mike; Williamson, Paula; Tudur Smith, Catrin

2016-01-01

Objectives Evaluate current data sharing activities of UK publicly funded Clinical Trial Units (CTUs) and identify good practices and barriers. Study Design and Setting Web-based survey of Directors of 45 UK Clinical Research Collaboration (UKCRC)–registered CTUs. Results Twenty-three (51%) CTUs responded: Five (22%) of these had an established data sharing policy and eight (35%) specifically requested consent to use patient data beyond the scope of the original trial. Fifteen (65%) CTUs had received requests for data, and seven (30%) had made external requests for data in the previous 12 months. CTUs supported the need for increased data sharing activities although concerns were raised about patient identification, misuse of data, and financial burden. Custodianship of clinical trial data and requirements for a CTU to align its policy to their parent institutes were also raised. No CTUs supported the use of an open access model for data sharing. Conclusion There is support within the publicly funded UKCRC-registered CTUs for data sharing, but many perceived barriers remain. CTUs are currently using a variety of approaches and procedures for sharing data. This survey has informed further work, including development of guidance for publicly funded CTUs, to promote good practice and facilitate data sharing. PMID:26169841

Cognitive rehabilitation for memory deficits following stroke.

PubMed

Majid, M J; Lincoln, N B; Weyman, N

2000-01-01

Memory problems occur following stroke. Cognitive rehabilitation programmes are provided to retrain memory function or to teach patients strategies to cope despite memory impairment. To determine the effects of cognitive rehabilitation for memory problems following stroke. We searched the Cochrane Stroke Group Trials Register, Medline, EMBASE, CINHAL and CLIN PSYCH databases and reference lists from relevant articles. Date of most recent searches: December 1998. Controlled trials of memory retraining in stroke. Studies with mixed aetiology groups were excluded unless they had more than 75% of stroke patients or separate data were available for the stroke patients. Two reviewers extracted trial data and assessed trial quality. Reviewers contacted investigators for further details of trials. One trial was identified with 12 participants. This showed memory strategy training had no significant effect on memory impairment or subjective memory complaints. There is insufficient evidence to support or refute the effectiveness of cognitive rehabilitation for memory problems after stroke.

Losigamone add-on therapy for partial epilepsy.

PubMed

Xiao, Yousheng; Luo, Man; Wang, Jin; Luo, Hongye

2015-12-10

Epilepsy is a common neurologic disorder, affecting approximately 50 million people worldwide; nearly a third of these people are not well controlled by a single antiepileptic drug (AED) and usually require treatment with a combination of two or more AEDs. In recent years, many newer AEDs have been investigated as add-on therapy for partial epilepsy; losigamone is one of these drugs and is the focus of this systematic review. This is an update of a Cochrane review first published in 2012 (Cochrane Database of Systematic Reviews 2012, Issue 6). To investigate the efficacy and safety of losigamone when used as an add-on therapy for partial epilepsy. We searched the Cochrane Epilepsy Group Specialized Register (16 February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 16 February 2015) and MEDLINE (Ovid, 1946 to 16 February 2015). We searched trials registers and contacted the manufacturer of losigamone and authors of included studies for additional information. We did not impose any language restrictions. Randomized controlled, add-on trials comparing losigamone with placebo for partial epilepsy. Two review authors independently assessed trial quality and extracted data. The primary outcomes were 50% or greater reduction in seizure frequency and seizure freedom; the secondary outcomes were treatment withdrawal and adverse events. Results are presented as risk ratios (RRs) with 95% confidence intervals (CIs) or 99% CIs (for the individual listed adverse events to make an allowance for multiple testing). Two trials involving a total of 467 patients, aged over 18 years, were eligible for inclusion. Both trials assessed losigamone 1200 mg/day or 1500 mg/day as an add-on therapy for partial epilepsy. One trial was assessed as being of good methodological quality while the other was of uncertain quality. For the efficacy outcomes, results did show patients taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.76; 95% CI 1.14 to 2.72), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16; 95% CI 1.28 to 3.67). For the safety outcomes, results indicated the proportion of patients who experienced adverse events in the losigamone group was higher than the placebo group (RR 1.34; 95% CI 1.00 to 1.80), dizziness was the only adverse event significantly reported in relation to losigamone (RR 3.82; 99% CI 1.69 to 8.64). The proportion of patients achieving seizure freedom was not reported in either trial report. A subgroup analysis according to different doses of losigamone showed that a higher dose of losigamone (1500 mg/day) was associated with a greater reduction in seizure frequency than lower doses, but was also associated with more dropouts due to adverse events. The results of this review showed losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with partial epilepsy. However, trials included were of short-term duration and uncertain quality. Future well-designed randomized, double-blind, placebo-controlled trials with a longer-term duration are needed. No new studies have been found since the last version of this review.

Development of an e-supported illness management and recovery programme for consumers with severe mental illness using intervention mapping, and design of an early cluster randomized controlled trial.

PubMed

Beentjes, Titus A A; van Gaal, Betsie G I; Goossens, Peter J J; Schoonhoven, Lisette

2016-01-19

E-mental health is a promising medium to keep mental health affordable and accessible. For consumers with severe mental illness the evidence of the effectiveness of e-health is limited. A number of difficulties and barriers have to be addressed concerning e-health for consumers with severe mental illness. One possible solution might be to blend e-health with face-to-face delivery of a recovery-oriented treatment, like the Illness Management & Recovery (IMR) programme. This paper describes the development of an e-health application for the IMR programme and the design of an early clustered randomized controlled trial. We developed the e-IMR intervention according to the six-step protocol of Intervention Mapping. Consumers joined the development group to address important and relevant issues for the target group. Decisions during the six-step development process were based on qualitative evaluations of the Illness Management & Recovery programme, structured interviews, discussion in the development group, and literature reviews on qualitative papers concerning consumers with severe mental illness, theoretical models, behavioural change techniques, and telemedicine for consumers with severe mental illness. The aim of the e-IMR intervention is to help consumers with severe mental illness to involve others, manage achieving goals, and prevent relapse. The e-IMR intervention consists of face-to-face delivery of the Illness Management & Recovery programme and an e-health application containing peer-testimonials on videos, follow up on goals and coping strategies, monitoring symptoms, solving problems, and communication opportunities. We designed an early cluster randomized controlled trial that will evaluate the e-IMR intervention. In the control condition the Illness Management & Recovery programme is provided. The main effect-study parameters are: illness management, recovery, psychiatric symptoms severity, self-management, quality of life, and general health. The process of the IMR program will be evaluated on fidelity and feasibility in semi-structured interviews with participants and trainers. Intervention Mapping provided a systematic procedure for the development of this e-health intervention for consumers with severe mental illness and the preparation of an early randomized controlled trial. The trial is registered in the Dutch Trial Register: NTR4772 .

Feasibility of high-intensity interval training and moderate-intensity continuous training in adults with inactive or mildly active Crohn's disease: study protocol for a randomised controlled trial.

PubMed

Tew, Garry A; Carpenter, Roger; Seed, Michael; Anderson, Simon; Langmead, Louise; Fairhurst, Caroline; Bottoms, Lindsay

2017-01-01

Structured exercise training has been proposed as a useful adjunctive therapy for Crohn's disease by improving immune function and psychological health, reducing fatigue and promoting gains in muscle and bone strength. However, the evidence for exercise in Crohn's disease is sparse, with only a handful of small prospective trials [1, 2], with methodological limitations, including the use of non-randomised and non-controlled study designs and small sample sizes. Here, we describe the protocol for a study that aims to assess the feasibility and acceptability of two common types of exercise training-high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT)-in adults with inactive or mildly active Crohn's disease (CD). This is a randomised, controlled, assessor-blinded, feasibility trial with three parallel groups. Forty-five adults with inactive or mildly active Crohn's disease will be randomly assigned 1:1:1 to HIIT, MICT or usual care control. Participants in the HIIT and MICT groups will be invited to undertake three sessions of supervised exercise each week for 12 consecutive weeks. HIIT sessions will consist of ten 1-min intervals of cycling exercise at 90% of peak power output separated by 1 min of active recovery. MICT sessions will involve 30 min of continuous cycling at 35% of peak power output. Participants will be assessed before randomisation and 13 and 26 weeks after randomisation. Feasibility outcomes include rates of recruitment, retention and adherence. Interviews with participants will explore the acceptability of the exercise programmes and study procedures. Clinical/health outcomes include cardiorespiratory fitness, body mass index, resting blood pressure, markers of disease activity (faecal calprotectin and Crohn's Disease Activity Index) and activated T cell cytokine profiles. Study questionnaires include the Inflammatory Bowel Disease Quality of Life Questionnaire, EQ-5D-5L, IBD Fatigue Scale, Hospital and Anxiety Depression Scale, and International Physical Activity Questionnaire. This study will provide useful information on the feasibility and acceptability of supervised exercise training in adults with inactive and mildly active Crohn's disease and will inform the design of a subsequent, adequately powered, multi-centre trial. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN13021107). Date registration assigned was 02/12/2015.

Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials.

PubMed

Walter, Martin A; Briel, Matthias; Christ-Crain, Mirjam; Bonnema, Steen J; Connell, John; Cooper, David S; Bucher, Heiner C; Müller-Brand, Jan; Müller, Beat

2007-03-10

To determine the effect of adjunctive antithyroid drugs on the risk of treatment failure, hypothyroidism, and adverse events after radioiodine treatment. Meta-analysis. Electronic databases (Cochrane central register of controlled trials, Medline, Embase) searched to August 2006 and contact with experts. Review methods Three reviewers independently assessed trial eligibility and quality. Pooled relative risks for treatment failure and hypothyroidism after radioiodine treatment with and without adjunctive antithyroid drugs were calculated with a random effects model. We identified 14 relevant randomised controlled trials with a total of 1306 participants. Adjunctive antithyroid medication was associated with an increased risk of treatment failure (relative risk 1.28, 95% confidence interval 1.07 to 1.52; P=0.006) and a reduced risk for hypothyroidism (0.68, 0.53 to 0.87; P=0.006) after radioiodine treatment. We found no difference in summary estimates for the different antithyroid drugs or for whether antithyroid drugs were given before or after radioiodine treatment. Antithyroid drugs potentially increase rates of failure and reduce rates of hypothyroidism if they are given in the week before or after radioiodine treatment, respectively.

Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy.

PubMed

Shang, Aijing; Huwiler-Müntener, Karin; Nartey, Linda; Jüni, Peter; Dörig, Stephan; Sterne, Jonathan A C; Pewsner, Daniel; Egger, Matthias

Homoeopathy is widely used, but specific effects of homoeopathic remedies seem implausible. Bias in the conduct and reporting of trials is a possible explanation for positive findings of trials of both homoeopathy and conventional medicine. We analysed trials of homoeopathy and conventional medicine and estimated treatment effects in trials least likely to be affected by bias. Placebo-controlled trials of homoeopathy were identified by a comprehensive literature search, which covered 19 electronic databases, reference lists of relevant papers, and contacts with experts. Trials in conventional medicine matched to homoeopathy trials for disorder and type of outcome were randomly selected from the Cochrane Controlled Trials Register (issue 1, 2003). Data were extracted in duplicate and outcomes coded so that odds ratios below 1 indicated benefit. Trials described as double-blind, with adequate randomisation, were assumed to be of higher methodological quality. Bias effects were examined in funnel plots and meta-regression models. 110 homoeopathy trials and 110 matched conventional-medicine trials were analysed. The median study size was 65 participants (range ten to 1573). 21 homoeopathy trials (19%) and nine (8%) conventional-medicine trials were of higher quality. In both groups, smaller trials and those of lower quality showed more beneficial treatment effects than larger and higher-quality trials. When the analysis was restricted to large trials of higher quality, the odds ratio was 0.88 (95% CI 0.65-1.19) for homoeopathy (eight trials) and 0.58 (0.39-0.85) for conventional medicine (six trials). Biases are present in placebo-controlled trials of both homoeopathy and conventional medicine. When account was taken for these biases in the analysis, there was weak evidence for a specific effect of homoeopathic remedies, but strong evidence for specific effects of conventional interventions. This finding is compatible with the notion that the clinical effects of homoeopathy are placebo effects.

Vector and reservoir control for preventing leishmaniasis.

PubMed

González, Urbà; Pinart, Mariona; Sinclair, David; Firooz, Alireza; Enk, Claes; Vélez, Ivan D; Esterhuizen, Tonya M; Tristan, Mario; Alvar, Jorge

2015-08-05

Leishmaniasis is caused by the Leishmania parasite, and transmitted by infected phlebotomine sandflies. Of the two distinct clinical syndromes, cutaneous leishmaniasis (CL) affects the skin and mucous membranes, and visceral leishmaniasis (VL) affects internal organs. Approaches to prevent transmission include vector control by reducing human contact with infected sandflies, and reservoir control, by reducing the number of infected animals. To assess the effects of vector and reservoir control interventions for cutaneous and for visceral leishmaniasis. We searched the following databases to 13 January 2015: Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS and WHOLIS, Web of Science, and RePORTER. We also searched trials registers for ongoing trials. Randomized controlled trials (RCTs) evaluating the effects of vector and reservoir control interventions in leishmaniasis-endemic regions. Two review authors independently searched for trials and extracted data from included RCTs. We resolved any disagreements by discussion with a third review author. We assessed the quality of the evidence using the GRADE approach. We included 14 RCTs that evaluated a range of interventions across different settings. The study methods were generally poorly described, and consequently all included trials were judged to be at high or unclear risk of selection and reporting bias. Only seven trials reported clinical outcome data which limits our ability to make broad generalizations to different epidemiological settings and cultures. Cutaneous leishmaniasisOne four-arm RCT from Afghanistan compared indoor residual spraying (IRS), insecticide-treated bednets (ITNs), and insecticide-treated bedsheets, with no intervention. Over 15 months follow-up, all three insecticide-based interventions had a lower incidence of CL than the control area (IRS: risk ratio (RR) 0.61, 95% confidence interval (CI) 0.38 to 0.97, 2892 participants, moderate quality evidence; ITNs: RR 0.32, 95% CI 0.18 to 0.56, 2954 participants, low quality evidence; ITS: RR 0.34, 95% CI 0.20 to 0.57, 2784 participants, low quality evidence). No difference was detected between the three interventions (low quality evidence). One additional trial of ITNs from Iran was underpowered to show a difference.Insecticide treated curtains were compared with no intervention in one RCT from Venezuela, where there were no CL episodes in the intervention areas over 12 months follow-up compared to 142 in control areas (RR 0.00, 95% CI 0.00 to 0.49, one trial, 2938 participants, low quality evidence).Personal protection using insecticide treated clothing was evaluated by two RCTs in soldiers, but the trials were underpowered to reliably detect effects on the incidence of CL (RR 0.40, 95% CI 0.13 to 1.20, two trials, 558 participants, low quality evidence). Visceral leishmaniasisIn a single RCT of ITNs versus no intervention from India and Nepal, the incidence of VL was low in both groups and no difference was detected (RR 0.99, 95% CI 0.46 to 2.15, one trial, 19,810 participants, moderate quality evidence).Two trials from Brazil evaluated the effects of culling infected dogs compared to no intervention or IRS. Although they report a reduction in seroconversion over 18 months follow-up, they did not measure or report effects on clinical disease. Using insecticides to reduce phlebotomine sandfly numbers may be effective at reducing the incidence of CL, but there is insufficient evidence from trials to know whether it is better to spray the internal walls of houses or to treat bednets, curtains, bedsheets or clothing.

Protocol of randomized control trial for effectiveness of angiotensin receptor blockers on blood pressure control among euvolemic hypertensive hemodialysis patients

PubMed Central

Aftab, Raja Ahsan; Khan, Amer Hayat; Syed Sulaiman, Syed Azhar; Khan, Tahir Mehmood; Adnan, Azreen Syazril

2017-01-01

Abstract Introduction: Volume overload and the renin–aldosterone–angiotensin system (RAAS) are 2 major factors contributing to hypertension (HTN) among hemodialysis (HD) patients. Although volume-dependent components of HTN can be corrected by appropriate volume removal, a proportion of HD patients experience elevated blood pressure (BP) despite achieving euvolemic and ideal dry weight. Method and analysis: A single center, prospective, randomized, parallel design, single-blind trial will be conducted in the Malaysian state of Kelantan among postdialysis euvolemic hypertensive patients that are on regular dialysis at least 3 times a week. The primary outcome of the trial will be to note the effectiveness of losartan (RAAS inhibitor) in reducing systolic BP < 140 mm Hg compared to standard non-RAAS-inhibitor antihypertensive therapy. The secondary outcome will be to look at all causes of mortality. A body composition monitor (BCM) will be used to assess postdialysis volume and dry weight. Postdialysis euvolemic patients that have systolic BP > 140 mm Hg will be randomized using Covariate Adaptive Randomization to standard or treatment arm. Participants in the treatment arm will be given 50 mg of losartan once daily except on dialysis days, whereas the standard arm patients will be prescribed non-RAAS antihypertensive agents. The study participants will be followed for a period of 12 months. A Wilcoxon statistical test will be performed to note the difference in BP from baseline up to 12 months using Statistical Package for the Social Sciences (SPSS) 20. Ethical and trial registration: The study protocols are approved from the Ethical and Research Committee of the Universiti Sains Malaysia (USM/JEPeM/15050173). The trial is registered under the Australia New Zealand Clinical Trial Registry (ACTRN12615001322527). The trial was registered on 2/12/2015 and the 1st patient was enrolled on 10/12/2015. The trial was formally initiated on 16/02/2016. Conclusion: Management of HTN among HD patients requires understanding the primary cause of HTN and treating accordingly. The current trial is an attempt to reduce BP among postdialysis euvolemic but hypertensive patients. PMID:28383400

Efficacy and safety of acupuncture for chronic dizziness: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Dizziness is one of the most challenging symptoms in medicine. No medication for dizziness in current use has well-established curative or prophylactic value or is suitable for long-term palliative use. Unconventional remedies, such as acupuncture, should be considered and scientifically evaluated. However, there has been relatively little evidence in randomized controlled clinical trials on acupuncture to treat chronic dizziness. The aim of our study is to evaluate the efficacy and safety of acupuncture in patients with dizziness. Methods/Design This trial is a randomized, single-blind, controlled study. A total of 80 participants will be randomly assigned to two treatment groups receiving acupuncture and sham acupuncture treatment, respectively, for 4 weeks. The primary outcome measures are the Dizziness Handicap Inventory (DHI) and the Vertigo Symptom Scale (VSS). Treatment will be conducted over a period of 4 weeks, at a frequency of two sessions per week. The assessment is at baseline (before treatment initiation), 4 weeks after the first acupuncture session, and 8 weeks after the first acupuncture session. Discussion The results from this study will provide clinical evidence on the efficacy and safety of acupuncture in patients with chronic dizziness. Trial registration International Standard Randomized Controlled Trial Number Register: ISRCTN52695239 PMID:24330810

Vitamin E supplementation in people with cystic fibrosis.

PubMed

Okebukola, Peter O; Kansra, Sonal; Barrett, Joanne

2014-12-09

People with cystic fibrosis are at an increased risk of fat-soluble vitamin deficiency including vitamin E. Vitamin E deficiency can cause a host of conditions such as haemolytic anaemia, cerebellar ataxia and cognitive difficulties. Vitamin E supplementation is widely recommended in cystic fibrosis and aims to ameliorate this deficiency. To determine the effects of any level of vitamin E supplementation on the frequency of vitamin E deficiency disorders in people with cystic fibrosis. We searched the Cochrane Group's Cystic Fibrosis Trials Register and also searched international trial registers for any ongoing clinical trials that were not identified during our register search.Date of last search of the Register: 10 February 2014. Date of last search of international trial registers: 30 August 2014. Randomised controlled trials and quasi-randomised controlled trials comparing any preparation of vitamin E supplementation to placebo or no supplement, regardless of dosage or duration. Two authors extracted outcome data from each study (published information) and assessed the risk of bias of each included study. Four studies with a total of 141 participants were included in the review, two of these were in children (aged six months to 14.5 years), and the other two did not specify participants' age. All studies used different formulations and doses of vitamin E for various durations of treatment (10 days to six months). Two studies compared the supplementation of fat-soluble as well as water-soluble formulations to no supplementation in different arms of the same study. A third study compared a water-soluble formulation to a placebo; and in the fourth study a fat-soluble formulation of vitamin E was assessed against placebo.At one month, three months and six months, water-soluble vitamin E significantly improved serum vitamin E levels compared with control: at one month, two studies, mean difference 17.66 (95% confidence interval 10.59 to 24.74); at three months, one study, mean difference 11.61 (95% confidence interval 4.77 to 18.45); and at six months, one study, mean difference 19.74 (95% confidence interval 13.48 to 26.00). At one month fat-soluble vitamin E significantly improved serum vitamin E levels compared with control: one month, two studies, mean difference 13.59 (95% CI 9.52 to 17.66). The findings at three months were imprecise; one study; mean difference 6.40 (95% CI -1.45 to 14.25).None of the studies report the review's primary outcomes of vitamin E total lipid ratio or the incidence of vitamin E-specific deficiency disorders, or the secondary outcomes lung function or quality of life. Only one study, comparing water-soluble vitamin E with placebo, reported the secondary outcome of growth and nutritional status (weight), but the results are uncertain due to imprecision around the effect estimate.There was limited detail about randomisation and blinding in the included studies which compromises the quality of the evidence base for the review. The heterogeneous mix of the formulations with differing biovailabilities among these studies also limits the generalisability of the data to the wider cystic fibrosis population. Vitamin E supplementation led to an improvement in vitamin E levels in people with cystic fibrosis, although the studies may have been at risk of bias. No data on other outcomes of interest were available to allow conclusions about any other benefits of this therapy.In future, larger studies are needed, especially in people already being treated with enteric-coated pancreatic enzymes and supplemented with vitamin E, to look at more specific outcome measures such as vitamin E status, lung function and nutritional status. Future studies could also look at the optimal dose of vitamin E required to achieve maximal clinical effectiveness.

Vitamin E supplementation in people with cystic fibrosis.

PubMed

Okebukola, Peter O; Kansra, Sonal; Barrett, Joanne

2017-03-06

People with cystic fibrosis are at an increased risk of fat-soluble vitamin deficiency including vitamin E. Vitamin E deficiency can cause a host of conditions such as haemolytic anaemia, cerebellar ataxia and cognitive difficulties. Vitamin E supplementation is widely recommended in cystic fibrosis and aims to ameliorate this deficiency. This is an updated version of the review. To determine the effects of any level of vitamin E supplementation on the frequency of vitamin E deficiency disorders in people with cystic fibrosis. We searched the Cochrane Group's Cystic Fibrosis Trials Register and also searched international trial registers for any ongoing clinical trials that were not identified during our register search.Date of last search of the Register: 10 October 2016. Date of last search of international trial registers: 15 February 2017. Randomised controlled trials and quasi-randomised controlled trials comparing any preparation of vitamin E supplementation to placebo or no supplement, regardless of dosage or duration. Two authors extracted outcome data from each study (published information) and assessed the risk of bias of each included study. Four studies with a total of 141 participants were included in the review, two of these were in children (aged six months to 14.5 years), and the other two did not specify participants' age. All studies used different formulations and doses of vitamin E for various durations of treatment (10 days to six months). Two studies compared the supplementation of fat-soluble as well as water-soluble formulations to no supplementation in different arms of the same study. A third study compared a water-soluble formulation to a placebo; and in the fourth study a fat-soluble formulation of vitamin E was assessed against placebo.At one month, three months and six months, water-soluble vitamin E significantly improved serum vitamin E levels compared with control: at one month, two studies, mean difference 17.66 (95% confidence interval 10.59 to 24.74); at three months, one study, mean difference 11.61 (95% confidence interval 4.77 to 18.45); and at six months, one study, mean difference 19.74 (95% confidence interval 13.48 to 26.00). At one month fat-soluble vitamin E significantly improved serum vitamin E levels compared with control: one month, two studies, mean difference 13.59 (95% CI 9.52 to 17.66). The findings at three months were imprecise; one study; mean difference 6.40 (95% confidence interval -1.45 to 14.25).None of the studies report the review's primary outcomes of vitamin E total lipid ratio or the incidence of vitamin E-specific deficiency disorders, or the secondary outcomes lung function or quality of life. Only one study, comparing water-soluble vitamin E with placebo, reported the secondary outcome of growth and nutritional status (weight), but the results are uncertain due to imprecision around the effect estimate.There was limited detail about randomisation and blinding in the included studies which compromises the quality of the evidence base for the review. The heterogeneous mix of the formulations with differing biovailabilities among these studies also limits the generalisability of the data to the wider cystic fibrosis population. Vitamin E supplementation led to an improvement in vitamin E levels in people with cystic fibrosis, although the studies may have been at risk of bias. No data on other outcomes of interest were available to allow conclusions about any other benefits of this therapy.In future, larger studies are needed, especially in people already being treated with enteric-coated pancreatic enzymes and supplemented with vitamin E, to look at more specific outcome measures such as vitamin E status, lung function and nutritional status. Future studies could also look at the optimal dose of vitamin E required to achieve maximal clinical effectiveness.

Clinical Perspectives from Randomized Phase 3 Trials on Prostate Cancer: An Analysis of the ClinicalTrials.gov Database.

PubMed

Tsikkinis, Alexandros; Cihoric, Nikola; Giannarini, Gianluca; Hinz, Stefan; Briganti, Alberto; Wust, Peter; Ost, Piet; Ploussard, Guillaume; Massard, Christophe; Surcel, Cristian I; Sooriakumaran, Prasanna; Isbarn, Hendrik; De Visschere, Peter J L; Futterer, Jurgen J; van der Bergh, Roderick C N; Dal Pra, Alan; Aebersold, Daniel M; Budach, Volker; Ghadjar, Pirus

2015-09-01

It is not easy to overview pending phase 3 trials on prostate cancer (PCa), and awareness of these trials would benefit clinicians. To identify all phase 3 trials on PCa registered in the ClinicalTrials.gov database with pending results. On September 29, 2014, a database was established from the records for 175 538 clinical trials registered on ClinicalTrials.gov. A search of this database for the substring "prostat" identified 2951 prostate trials. Phase 3 trials accounted for 441 studies, of which 333 concerned only PCa. We selected only ongoing or completed trials with pending results, that is, for which the primary endpoint had not been published in a peer-reviewed medical journal. We identified 123 phase 3 trials with pending results. Trials were conducted predominantly in North America (n=63; 51%) and Europe (n=47; 38%). The majority were on nonmetastatic disease (n=82; 67%), with 37 (30%) on metastatic disease and four trials (3%) including both. In terms of intervention, systemic treatment was most commonly tested (n=71; 58%), followed by local treatment 34 (28%), and both systemic and local treatment (n=11; 9%), with seven (6%) trials not classifiable. The 71 trials on systemic treatment included androgen deprivation therapy (n=34; 48%), chemotherapy (n=15; 21%), immunotherapy (n=9; 13%), other systemic drugs (n=9; 13%), radiopharmaceuticals (n=2; 3%), and combinations (n=2; 3%). Local treatments tested included radiation therapy (n=27; 79%), surgery (n=5; 15%), and both (n=2; 2%). A limitation is that not every clinical trial is registered on ClinicalTrials.gov. There are many PCa phase 3 trials with pending results, most of which address questions regarding systemic treatments for both nonmetastatic and metastatic disease. Radiation therapy and androgen deprivation therapy are the interventions most commonly tested for local and systemic treatment, respectively. This report describes all phase 3 trials on prostate cancer registered in the ClinicalTrials.gov database with pending results. Most of these trials address questions regarding systemic treatments for both nonmetastatic and metastatic disease. Radiation therapy and androgen deprivation therapy are the interventions most commonly tested for local and systemic treatment, respectively. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

BTS randomised feasibility study of active symptom control with or without chemotherapy in malignant pleural mesothelioma: ISRCTN 54469112.

PubMed

Muers, M F; Rudd, R M; O'Brien, M E R; Qian, W; Hodson, A; Parmar, M K B; Girling, D J

2004-02-01

The incidence of mesothelioma is rising rapidly in the UK. There is no generally accepted standard treatment. The BTS recommends active symptom control (ASC). It is not known whether chemotherapy in addition prolongs survival or provides worthwhile palliation with acceptable toxicity. Palliation as recorded by patients has been fully reported for only two regimens: mitomycin, vinblastine, and cisplatin (MVP), and vinorelbine (N). The BTS and collaborators planned to conduct a phase III randomised trial comparing ASC only, ASC+MVP, and ASC+N in 840 patients with survival as the primary outcome measure. The aim of the present study was to assess the acceptability of the trial design to patients and the suitability of two standard quality of life (QL) questionnaires for mesothelioma. Collaborating centres registered all new patients with mesothelioma. Those eligible and giving informed consent completed EORTC QLQ-C30+LC13 and FACT-L QL questionnaires and were randomised between all three or any two of (1) ASC only, (2) ASC+4 cycles of MVP, and (3) ASC+12 weekly doses of N. During 1 year, 242 patients were registered of whom 109 (45%) were randomised (55% of the 197 eligible patients). Fifty two patients from 20 centres were randomised to an option including ASC only. This translates into a rate of 312 per year from 60 centres interested in collaborating in the phase III trial. The EORTC QL questionnaire was superior to FACT-L in terms of completeness of data and patient preference. Clinically relevant palliation was achieved with ASC. The planned phase III trial is feasible.

Magnetic resonance imaging for cerebral lesions during minimal invasive mitral valve surgery: study protocol for a randomized controlled trial.

PubMed

Barbero, Cristina; Ricci, Davide; Cura Stura, Erik; Pellegrini, Augusto; Marchetto, Giovanni; ElQarra, Suad; Boffini, Massimo; Passera, Roberto; Valentini, Maria Consuelo; Rinaldi, Mauro

2017-02-21

Recent data have highlighted a higher rate of neurological injuries in minimal invasive mitral valve surgery (MIMVS) compared with the standard sternotomy approach; therefore, the role of specific clamping techniques and perfusion strategies on the occurrence of this complication is a matter of discussion in the medical literature. The purpose of this trial is to prospectively evaluate major, minor and silent neurological events in patients undergoing right mini-thoracotomy mitral valve surgery using retrograde perfusion and an endoaortic clamp or a transthoracic clamp. A prospective, blinded, randomized controlled study on the rate of neurological embolizations during MIMVS started at the University of Turin in June 2014. Major, minor and silent neurological events are being investigated through standard neurological evaluation and magnetic resonance imaging assessment. The magnetic resonance imaging protocol includes conventional sequences for the morphological and quantitative assessment and nonconventional sequences for the white matter microstructural evaluation. Imaging studies are performed before surgery as baseline assessment and on the third postoperative day and, in patients who develop postoperative ischemic lesions, after 6 months. Despite recent concerns raised about the endoaortic setting with retrograde perfusion, we expect to show equivalence in terms of neurological events of this technique compared with the transthoracic clamp in a selected cohort of patients. With the first results expected in December 2016 the findings would be of help in confirming the efficacy and safety of MIMVS. ClinicalTrials.gov, Identifier: NCT02818166 . Registered on 8 February 2016 - trial retrospectively registered.

Does Goal Attainment Scaling improve satisfaction regarding performance of activities of younger knee arthroplasty patients? Study protocol of the randomized controlled ACTION trial.

PubMed

Witjes, Suzanne; Hoorntje, Alexander; Kuijer, P Paul F M; Koenraadt, Koen L M; Blankevoort, Leendert; Kerkhoffs, Gino M M J; van Geenen, Rutger C I

2016-03-02

Knee arthroplasty is being increasingly performed, and also more often in a younger patient population (<65 years of age). Up to 20 % of patients remain dissatisfied after knee arthroplasty, despite the apparent technical success of the operation. Recent studies suggest that the fulfilment of patients' expectations plays an important role in achieving satisfaction. Thus, addressing preoperative expectations more explicitly might improve patient satisfaction. The primary aim of the present study is to investigate the effect of a multidisciplinary, goal attained and individualized rehabilitation on satisfaction of activities of younger patients (<65 years) after knee arthroplasty. A single-centre randomized controlled trial will be conducted. In total, 120 patients (<65 years of age) with knee osteoarthritis who will undergo knee arthroplasty, will be randomly allocated to either goal attainment scaling rehabilitation or usual care rehabilitation. Goal attainment scaling rehabilitation includes drafting individually set rehabilitation goals preoperatively and measuring progress of rehabilitation on a six-point scale (-3 to +2). The primary outcome is patient satisfaction concerning activities in daily life, work and leisure time, including sports. Secondary outcome measures include KOOS, OKS, SQUASH and WORQ questionnaires and activity objectively measured with the Activ8® activity monitor. The findings of this study will help to elucidate whether goal attainment scaling is an effective rehabilitation method for achieving higher levels of patient satisfaction, with a focus on activities, in younger patients after knee arthroplasty. This trial is since June 15(th) 2015 registered at the Dutch Trial Register: NTR5251 .

Effects and feasibility of a multi-disciplinary orientation program for newly registered cancer patients: design of a randomised controlled trial.

PubMed

Chan, Raymond; Webster, Joan; Bennett, Linda

2009-11-11

Diagnosis and treatment of cancer can contribute to psychological distress and anxiety amongst patients. Evidence indicates that information giving can be beneficial in reducing patient anxiety, so oncology specific information may have a major impact on this patient group. This study investigates the effects of an orientation program on levels of anxiety and self-efficacy amongst newly registered cancer patients who are about to undergo chemotherapy and/or radiation therapy in the cancer care centre of a large tertiary Australian hospital. The concept of interventions for orienting new cancer patients needs revisiting due to the dynamic health care system. Historically, most orientation programs at this cancer centre were conducted by one nurse. A randomised controlled trial has been designed to test the effectiveness of an orientation program with bundled interventions; a face-to-face program which includes introduction to the hospital facilities, introduction to the multi-disciplinary team and an overview of treatment side effects and self care strategies. The aim is to orientate patients to the cancer centre and to meet the health care team. We hypothesize that patients who receive this orientation will experience lower levels of anxiety and distress, and a higher level of self-efficacy. An orientation program is a common health care service provided by cancer care centres for new cancer patients. Such programs aim to give information to patients at the beginning of their encounter at a cancer care centre. It is clear in the literature that interventions that aim to improve self-efficacy in patients may demonstrate potential improvement in health outcomes. Yet, evidence on the effects of orientation programs for cancer patients on self-efficacy remains scarce, particularly with respect to the use of multidisciplinary team members. This paper presents the design of a randomised controlled trial that will evaluate the effects and feasibility of a multidisciplinary orientation program for new cancer patients. Current Controlled Trials ACTRN12609000018213.

The effectiveness of occlusal splints for sleep bruxism.

PubMed

Jagger, Robert

2008-01-01

Searches were made using the Cochrane Oral Health Group's Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, LILACS (Latin American & Caribbean Health Sciences Literature), Biblioteca Brasileira de Odontologia, and Dissertations, Theses and Abstracts. Hand searches were made of abstracts of particular importance to this review. Additional reports were identified from the reference lists of retrieved reports and from article reviews about treating sleep bruxism. There were no language restrictions. Randomised controlled trials (RCT) or quasi-RCT were chosen that compared splint therapy concurrently with no treatment, other occlusal appliances, or any other intervention in participants who had sleep bruxism. Data extraction was carried out independently and in duplicate. Validity assessment of the included trials was carried out at the same time as data extraction. Discrepancies were discussed and a third review author consulted. The author of the primary study was contacted when necessary. Thirty-two potentially relevant RCT were identified of which five were eventually included. In these, use of an occlusal splint was compared with palatal splint, mandibular advancement device, transcutaneous electric nerve stimulation, and no treatment. There was just one common outcome (arousal index) which was combined in a meta-analysis. No statistically significant difference between the occlusal splint and control groups were found in meta-analysis. There is not enough evidence to state that the occlusal splint is effective for treating sleep bruxism. Indication of its use is questionable with regard to sleep outcomes, but there may be some benefit with regard to tooth wear. This systematic review suggests the need for further investigation in more controlled RCT that pay attention to method of allocation, outcome assessment, large sample size, and sufficient duration of followup. The study design must be parallel in order to eliminate the bias provided by studies of crossover type. A standardisation of the outcomes of the treatment of sleep bruxism should be established in the RCT.

Cost-effectiveness of the Australian Medical Sheepskin for the prevention of pressure ulcers in somatic nursing home patients: study protocol for a prospective multi-centre randomised controlled trial (ISRCTN17553857).

PubMed

Mistiaen, Patriek; Achterberg, Wilco; Ament, Andre; Halfens, Ruud; Huizinga, Janneke; Montgomery, Ken; Post, Henri; Francke, Anneke L

2008-01-07

Pressure ulcers are a major problem, especially in nursing home patients, although they are regarded as preventable and there are many pressure relieving methods and materials. One such pressure relieving material is the recently developed Australian Medical Sheepskin, which has been shown in two randomized controlled trials 12 to be an effective intervention in the prevention of sacral pressure ulcers in hospital patients. However, the use of sheepskins has been debated and in general discouraged by most pressure ulcer working groups and pressure ulcer guidelines, but these debates were based on old forms of sheepskins. Furthermore, nothing is yet known about the (cost-)effectiveness of the Australian Medical sheepskin in nursing home patients. The objective of this study is to assess the effects and costs of the use of the Australian Medical Sheepskin combined with usual care with regard to the prevention of sacral pressure ulcers in somatic nursing home patients, versus usual care only. In a multi-centre randomised controlled trial 750 patients admitted for a primarily somatic reason to one of the five participating nursing homes, and not having pressure ulcers on the sacrum at admission, will be randomized to either usual care only or usual care plus the use of the Australian Medical Sheepskin as an overlay on the mattress. Outcome measures are: incidence of sacral pressure ulcers in the first month after admission; sacrum pressure ulcer free days; costs; patient comfort; and ease of use. The skin of all the patients will be observed once a day from admission on for 30 days. Patient characteristics and pressure risk scores are assessed at admission and at day 30 after it. Additional to the empirical phase, systematic reviews will be performed in order to obtain data for economic weighting and modelling. The protocol is registered in the Controlled Trial Register as ISRCTN17553857.

Care delivery and self-management strategies for children with epilepsy.

PubMed

Fleeman, Nigel; Bradley, Peter M

2018-03-01

In response to criticism that epilepsy care for children has little impact, healthcare professionals and administrators have developed various service models and strategies to address perceived inadequacies. To assess the effects of any specialised or dedicated intervention for epilepsy versus usual care in children with epilepsy and in their families. We searched the Cochrane Epilepsy Group Specialized Register (27 September 2016), the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 9) in the Cochrane Library, MEDLINE (1946 to 27 September 2016), Embase (1974 to 27 September 2016), PsycINFO (1887 to 27 September 2016) and CINAHL Plus (1937 to 27 September 2016). In addition, we also searched clinical trials registries for ongoing or recently completed trials, contacted experts in the field to seek information on unpublished and ongoing studies, checked the websites of epilepsy organisations and checked the reference lists of included studies. We included randomised controlled trials (RCTs), cohort studies or other prospective studies with a (matched or unmatched) control group (controlled before-and-after studies), or time series studies. We used standard methodological procedures expected by Cochrane. Our review included six interventions reported through seven studies (of which five studies were designed as RCTs). They reported on different education and counselling programmes for children and parents; teenagers and parents; or children, adolescents and their parents. Each programme showed some benefits for the well-being of children with epilepsy, but all had methodological flaws (e.g. in one of the studies designed as an RCT, randomisation failed), no single programme was independently evaluated with different study samples and no interventions were sufficiently homogeneous enough to be included in a meta-analysis,. While each of the programmes in this review showed some benefit to children with epilepsy, their impacts were extremely variable. No programme showed benefits across the full range of outcomes, and all studies had major methodological problems. At present there is insufficient evidence in favour of any single programme.

A comparison of interventional clinical trials in rare versus non-rare diseases: an analysis of ClinicalTrials.gov.

PubMed

Bell, Stuart A; Tudur Smith, Catrin

2014-11-26

To provide a comprehensive characterisation of rare disease clinical trials registered in ClinicalTrials.gov, and compare against characteristics of trials in non-rare diseases. Registry based study of ClinicalTrials.gov registration entries. The ClinicalTrials.gov registry comprised 133,128 studies registered to September 27, 2012. By annotating medical subject heading descriptors to condition terms we could identify rare and non-rare disease trials. A total of 24,088 Interventional trials registered after January 1, 2006, conducted in the United States, Canada and/or the European Union were categorised as rare or non-rare. Characteristics of the respective trials were extracted and summarised with comparative statistics calculated where appropriate. Characteristics of interventional trials reported in the database categorised by rare and non-rare conditions to allow comparison. Of the 24,088 trials categorised 2,759 (11.5%) were classified as rare disease trials and 21,329 (88.5%) related to non-rare conditions. Despite the limitations of the database we found that rare disease trials differed to non-rare disease trials across all characteristics that we examined. Rare disease trials enrolled fewer participants (median 29 vs. 62), were more likely to be single arm (63.0% vs. 29.6%), non-randomised (64.5% vs. 36.1%) and open label (78.7% vs. 52.2%). A higher proportion of rare disease trials were terminated early (13.7% vs. 6.3%) and proportionally fewer rare disease studies were actively pursuing, or waiting to commence, enrolment (15.9% vs. 38.5%). Rare disease interventional trials differ from those in non-rare conditions with notable differences in enrolment, design, blinding and randomisation. However, clinical trials should aim to implement the highest trial design standards possible, regardless of whether diseases are rare or not.

Control of Visceral Leishmaniasis in Latin America—A Systematic Review

PubMed Central

Romero, Gustavo A. S.; Boelaert, Marleen

2010-01-01

Background While three countries in South Asia decided to eliminate anthroponotic visceral leishmaniasis (VL) by 2015, its control in other regions seems fraught with difficulties. Is there a scope for more effective VL control in the Americas where transmission is zoonotic? We reviewed the evidence on VL control strategies in Latin America—diagnosis, treatment, veterinary interventions, vector control—with respect to entomological and clinical outcomes. Methodology/Principal Findings We searched the electronic databases of MEDLINE, LILACS, and the Cochrane Central Register of Controlled Trials, from 1960 to November 2008 and references of selected articles. Intervention trials as well as observational studies that evaluated control strategies of VL in the Americas were included. While the use of rapid diagnostic tests for VL diagnosis seems well established, there is a striking lack of evidence from clinical trials for drug therapy and few well designed intervention studies for control of vectors or canine reservoirs. Conclusion Elimination of zoonotic VL in the Americas does not seem a realistic goal at this point given the lack of political commitment, gaps in scientific knowledge, and the weakness of case management and surveillance systems. Research priorities and current strategies should be reviewed with the aim of achieving better VL control. PMID:20098726

Controlled trials in children: quantity, methodological quality and descriptive characteristics of pediatric controlled trials published 1948-2006.

PubMed

Thomson, Denise; Hartling, Lisa; Cohen, Eyal; Vandermeer, Ben; Tjosvold, Lisa; Klassen, Terry P

2010-09-30

The objective of this study was to describe randomized controlled trials (RCTs) and controlled clinical trials (CCTs) in child health published between 1948 and 2006, in terms of quantity, methodological quality, and publication and trial characteristics. We used the Trials Register of the Cochrane Child Health Field for overall trends and a sample from this to explore trial characteristics in more detail. We extracted descriptive data on a random sample of 578 trials. Ninety-six percent of the trials were published in English; the percentage of child-only trials was 90.5%. The most frequent diagnostic categories were infectious diseases (13.2%), behavioural and psychiatric disorders (11.6%), neonatal critical care (11.4%), respiratory disorders (8.9%), non-critical neonatology (7.9%), and anaesthesia (6.5%). There were significantly fewer child-only studies (i.e., more mixed child and adult studies) over time (P = 0.0460). The proportion of RCTs to CCTs increased significantly over time (P<0.0001), as did the proportion of multicentre trials (P = 0.002). Significant increases over time were found in methodological quality (Jadad score) (P<0.0001), the proportion of double-blind studies (P<0.0001), and studies with adequate allocation concealment (P<0.0001). Additionally, we found an improvement in reporting over time: adequate description of withdrawals and losses to follow-up (P<0.0001), sample size calculations (P<0.0001), and intention-to-treat analysis (P<0.0001). However, many trials still do not describe their level of blinding, and allocation concealment was inadequately reported in the majority of studies across the entire time period. The proportion of studies with industry funding decreased slightly over time (P = 0.003), and these studies were more likely to report positive conclusions (P = 0.028). The quantity and quality of pediatric controlled trials has increased over time; however, much work remains to be done, particularly in improving methodological issues around conduct and reporting of trials.

Prostate cancer - evidence of exercise and nutrition trial (PrEvENT): study protocol for a randomised controlled feasibility trial.

PubMed

Hackshaw-McGeagh, Lucy; Lane, J Athene; Persad, Raj; Gillatt, David; Holly, Jeff M P; Koupparis, Anthony; Rowe, Edward; Johnston, Lyndsey; Cloete, Jenny; Shiridzinomwa, Constance; Abrams, Paul; Penfold, Chris M; Bahl, Amit; Oxley, Jon; Perks, Claire M; Martin, Richard

2016-03-07

A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The 'Prostate Cancer: Evidence of Exercise and Nutrition Trial' investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures. The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation). The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery. Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.

Pimozide for tics in Tourette's syndrome.

PubMed

Pringsheim, Tamara; Marras, Connie

2009-04-15

Neuroleptic drugs with potent D-2 receptor blocking properties have been the traditional treatment for tics caused by Tourette Syndrome. Pimozide is the most studied of these. Use of these medications is declining because of concerns about side effects, and new atypical neuroleptics are now available. The true benefit and risks associated with pimozide compared to other drugs is not known. To evaluate the efficacy and harms of pimozide in comparison to placebo or other medications in the treatment of tics in Tourette Syndrome. We cross-referenced pimozide and its proprietary names with Tourette Syndrome and its derivations, as MeSH headings and as text words, and searched the Cochrane Movement Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 4), MEDLINE (1950-April 2007), and EMBASE (1980-April 2007). Reference lists of relevant articles were reviewed for additional trials. All randomized, controlled, double blind studies comparing pimozide to placebo or other medications for the treatment of tics in Tourette Syndrome were considered for inclusion in this review. Both parallel group and crossover studies of children or adults, at any dose and for any duration, were included. Data was abstracted independently by two authors onto standardized forms and disagreements were resolved by discussion. Six randomized controlled trials were included (total 162 participants, age range 7 to 53 years). Pimozide was compared with: placebo and haloperidol (two trials), placebo (one trial), haloperidol (one trial), and risperidone (two trials). Methodological quality was rated 'fair' for all studies. Studies used different outcome measurement scales for assessing tic severity and adverse effects. Significant clinical heterogeneity made meta-analysis inappropriate. Pimozide was superior to placebo in three studies, though it caused more side effects than placebo in one of these. Pimozide was inferior to haloperidol in one of three studies (the other two showed no significant difference between the drugs), which also showed significantly fewer side effects associated with pimozide. No significant differences between pimozide and risperidone were detected. Pimozide is an effective treatment for tics in Tourette Syndrome, though the number of trials comparing its effect to placebo and other drugs is limited. Trials of longer duration (minimum six months) are needed to investigate the longer-term effects of pimozide compared to atypical neuroleptics. Future trials should use the Yale Global Tic Severity Scale to assess the main outcome measure, and quantify adverse events with the Extrapyramidal Symptoms Rating Scale.

Complement inhibitors for age-related macular degeneration.

PubMed

Williams, Michael A; McKay, Gareth J; Chakravarthy, Usha

2014-01-15

Given the relatively high prevalence of age-related macular degeneration (AMD) and the increased incidence of AMD as populations age, the results of trials of novel treatments are awaited with much anticipation. The complement cascade describes a series of proteolytic reactions occurring throughout the body that generate proteins with a variety of roles including the initiation and promotion of immune reactions against foreign materials or micro-organisms. The complement cascade is normally tightly regulated, but much evidence implicates complement overactivity in AMD and so it is a logical therapeutic target in the treatment of AMD. To assess the effects and safety of complement inhibitors in the prevention or treatment of advanced AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 11), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2013), EMBASE (January 1980 to November 2013), Allied and Complementary Medicine Database (AMED) (January 1985 to November 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2013), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), Web of Science Conference Proceedings Citation Index - Science (CPCI-S) (January 1990 to November 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 November 2013. We also performed handsearching of proceedings, from 2012 onwards, of meetings and conferences of specific professional organisations. We planned to include randomised controlled trials (RCTs) with parallel treatment groups which investigated either the prevention or treatment of advanced AMD by inhibition of the complement cascade. Two authors (MW and GMcK) independently evaluated all the titles and abstracts resulting from the searches. We contacted companies running clinical trials which had not yet reported results to request information. Since no trials met our inclusion criteria, we undertook no assessment of quality or meta-analysis. We identified and screened 317 references but there were no published RCTs that met the inclusion criteria. We identified two ongoing studies: one phase I study and one phase II study. There is insufficient information at present to generate evidence-based recommendations on the potential safety and efficacy of complement inhibitors for prevention or treatment of AMD. However we anticipate the results of ongoing trials.

Effects of self-ligating brackets on oral hygiene and discomfort: a systematic review and meta-analysis of randomized controlled clinical trials.

PubMed

Yang, X; Su, N; Shi, Z; Xiang, Z; He, Y; Han, X; Bai, D

2017-02-01

Self-ligating brackets (SLBs) are widely adopted in clinic owing to their claimed superiorities. Here, we collected and analysed all randomized controlled clinical trials (RCTs) comparing SLBs with conventional brackets (CBs) and thereby investigated whether SLBs can relieve discomfort or promote oral hygiene. Electronic databases including MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, World Health Organization International Clinical Trials Registry Platform, Chinese BioMedical Literature Database and the China National Knowledge Infrastructure were searched to find out RCTs comparing active or passive SLBs with CBs. Two reviewers extracted the data and assessed risks of bias independently. Any disagreement between them was resolved through discussion with a third reviewer. Meta-analysis was conducted on Review Manager 5.3. A total of 12 RCTs with 575 participants were included, and eight of the trials were synthesized quantitatively. Two trials were assessed as low risk of bias, whereas others as unclear risk of bias. Passive SLBs and CBs are not significantly different in plaque control. SLBs and CBs are not significantly different in discomfort reduction at any of four time points (4 h, 24 h, 3 days and 7 days). Clinical evidences from existing RCTs suggest that SLBs do not outperform CBs in reliving discomfort or promoting oral health in clinic. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects and Safety of Gyejibongnyeong-Hwan on Dysmenorrhea Caused by Blood Stagnation: A Randomized Controlled Trial

PubMed Central

Park, Jeong-Su; Park, Sunju; Cheon, Chun-Hoo; Jo, Seong-Cheon; Cho, Han Baek; Lim, Eun-Mee; Lim, Hyung Ho; Shin, Yong-Cheol; Ko, Seong-Gyu

2013-01-01

Objective. This study was a multicenter, randomized, double-blind, and controlled trial with two parallel arms: the GJBNH group and the placebo group. This trial recruited 100 women aging 18 to 35 years with primary dysmenorrhea caused by blood stagnation. The investigational drugs, GJBNH or placebo, were administered for two menstrual periods (8 weeks) to the participants three times per day. The participants were followed up for two menstrual cycles after the administration. Results. The results were analyzed by the intention-to-treat (ITT) dataset and the per-protocol (PP) dataset. In the ITT dataset, the change of the average menstrual pain VAS score in the GJBNH group was statistically significantly lower than that in the control group. Significant difference was not observed in the SF-MPQ score change between the GJBNH group and the placebo group. No significant difference was observed in the PP analyses. In the follow-up phase, the VAS scores of the average menstrual pain and the maximum menstrual pain continually decreased in the placebo group, but they increased in the GJBNH group. Conclusion. GJBNH treatment for eight weeks improved the pain of the dysmenorrhea caused by blood stagnation, but it should be successively administered for more than two menstrual cycles. Trial Registration. This trial is registered with Current Controlled Trials no. ISRCTN30426947. PMID:24191165

Efficacy of Acupuncture for Bell's Palsy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Li, Pingping; Qiu, Tangmeng; Qin, Chao

2015-01-01

Acupuncture has emerged as an alternative therapy for Bell's palsy in both adults and children. However, the use of acupuncture is controversial. We conducted a systematic review and meta-analysis to assess the efficacy of acupuncture for Bell's palsy. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, irrespective of any language restrictions. Randomized controlled trials comparing acupuncture with other therapies for Bell's palsy in adults or children were included. Fourteen randomized controlled trials involving 1541 individuals were included in this meta-analysis. Significant association was observed in acupuncture with a higher effective response rate for Bell's palsy (relative risk, 1.14; 95% confidence interval, 1.04-1.25; P = 0.005) but there was a heterogeneity among the studies (I2 = 87%). An assessment of the included studies revealed a high risk of bias in methodological quality. An evaluation of the incidence of complications was not available, owing to incomplete data. Acupuncture seems to be an effective therapy for Bell's palsy, but there was insufficient evidence to support the efficacy and safety of acupuncture. However, the results should be interpreted cautiously, because of the poor quality and heterogeneity of the included studies.

Effects of a Patient-Provider, Collaborative, Medication-Planning Tool: A Randomized, Controlled Trial

PubMed Central

Wolf, Michael S.; Kaiser, Darren; Morrow, Daniel G.

2016-01-01

Among patients with various levels of health literacy, the effects of collaborative, patient-provider, medication-planning tools on outcomes relevant to self-management are uncertain. Objective. Among adult patients with type II diabetes mellitus, we tested the effectiveness of a medication-planning tool (Medtable™) implemented via an electronic medical record to improve patients' medication knowledge, adherence, and glycemic control compared to usual care. Design. A multicenter, randomized controlled trial in outpatient primary care clinics. 674 patients received either the Medtable tool or usual care and were followed up for up to 12 months. Results. Patients who received Medtable had greater knowledge about indications for medications in their regimens and were more satisfied with the information about their medications. Patients' knowledge of drug indication improved with Medtable regardless of their literacy status. However, Medtable did not improve patients' demonstrated medication use, regimen adherence, or glycemic control (HbA1c). Conclusion. The Medtable tool supported provider/patient collaboration related to medication use, as reflected in patient satisfaction with communication, but had limited impact on patient medication knowledge, adherence, and HbA1c outcomes. This trial is registered with ClinicalTrials.gov NCT01296633. PMID:27699179

Employing open/hidden administration in psychotherapy research: A randomized-controlled trial of expressive writing

PubMed Central

Tondorf, Theresa; Kaufmann, Lisa-Katrin; Degel, Alexander; Locher, Cosima; Birkhäuer, Johanna; Gerger, Heike; Ehlert, Ulrike

2017-01-01

Psychotherapy has been shown to be effective, but efforts to prove specific effects by placebo-controlled trials have been practically and conceptually hampered. We propose that adopting open/hidden designs from placebo research would offer a possible way to establish specificity in psychotherapy. Therefore, we tested the effects of providing opposing treatment rationales in an online expressive writing intervention on affect in healthy subjects. Results indicate that it was possible to conduct the expressive writing intervention both covertly and openly, but that participants in the hidden administration condition did not fully benefit from the otherwise effective expressive writing intervention in the long-run. Effect sizes between open and hidden administration groups were comparable to pre-post effect sizes of the intervention. While this finding is important for the understanding of psychotherapy's effects per se, it also proves that alternative research approaches to establish specificity are feasible and informative in psychotherapy research. Trial registration: German Clinical Trials Register DRKS00009428 PMID:29176768

Role of supplemental calcium in the recurrence of colorectal adenomas: a metaanalysis of randomized controlled trials.

PubMed

Shaukat, Aasma; Scouras, Nicole; Schünemann, Holger J

2005-02-01

Colorectal adenomas are neoplastic growths that are important targets for chemoprevention. Dietary calcium is thought to play an important role in chemoprevention. However, the role of calcium supplementation for preventing recurrence of adenomas is controversial. We performed a systematic review and meta-analysis to study the role of calcium supplementation in preventing recurrence of adenomas. We searched electronic bibliographic databases (Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, CINAHL, EMBASE, and MEDLINE) and contacted authors to identify potentially eligible studies. We identified three trials including 1,485 subjects with previously removed adenomas who were randomized to calcium versus placebo supplementation. The study endpoint was recurrence of adenomas at the end of 3-4 yr in 1,279 patients who completed the trials. We found that the recurrence of adenomas was significantly lower in subjects randomized to calcium supplementation (RR: 0.80, CI: 0.68, 0.93; p-value = 0.004). This systematic review and meta-analysis suggest that calcium supplementation prevents recurrent colorectal adenomas.

Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection

PubMed Central

Henriquez-Camacho, Cesar; Gotuzzo, Eduardo; Echevarria, Juan; White, A Clinton; Terashima, Angelica; Samalvides, Frine; Pérez-Molina, José A; Plana, Maria N

2016-01-01

Background Strongyloidiasis is a gut infection with Strongyloides stercoralis which is common world wide. Chronic infection usually causes a skin rash, vomiting, diarrhoea or constipation, and respiratory problems, and it can be fatal in people with immune deficiency. It may be treated with ivermectin or albendazole or thiabendazole. Objectives To assess the effects of ivermectin versus benzimidazoles (albendazole and thiabendazole) for treating chronic strongyloides infection. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register (24 August 2015); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (January 1966 to August 2015); EMBASE (January 1980 to August 2015); LILACS (August 2015); and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) using 'strongyloid*' as a search term, reference lists, and conference abstracts. Selection criteria Randomized controlled trials of ivermectin versus albendazole or thiabendazole for treating chronic strongyloides infection. Data collection and analysis Two review authors independently extracted data and assessed risk of bias in the included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) and fixed- or random-effects models. We pooled adverse event data if the trials were sufficiently similar in their adverse event definitions. Main results We included seven trials, enrolling 1147 participants, conducted between 1994 and 2011 in different locations (Africa, Southeast Asia, America and Europe). In trials comparing ivermectin with albendazole, parasitological cure was higher with ivermectin (RR 1.79, 95% CI 1.55 to 2.08; 478 participants, four trials, moderate quality evidence). There were no statistically significant differences in adverse events (RR 0.80, 95% CI 0.59 to 1.09; 518 participants, four trials, low quality evidence). In trials comparing ivermectin with thiabendazole, there was little or no difference in parasitological cure (RR 1.07, 95% CI 0.96 to 1.20; 467 participants, three trials, low quality evidence). However, adverse events were less common with ivermectin (RR 0.31, 95% CI 0.20 to 0.50; 507 participants; three trials, moderate quality evidence). In trials comparing different dosages of ivermectin, taking a second dose of 200 μg/kg of ivermectin was not associated with higher cure in a small subgroup of participants (RR 1.02, 95% CI 0.94 to 1.11; 94 participants, two trials). Dizziness, nausea, and disorientation were commonly reported in all drug groups. There were no reports of serious adverse events or death. Authors' conclusions Ivermectin results in more people cured than albendazole, and is at least as well tolerated. In trials of ivermectin with thiabendazole, parasitological cure is similar but there are more adverse events with thiabendazole. Ivermectin versus benzimidazoles for treating Strongyloides stercoralis infection What is strongyloides infection and how might ivermectin work Strongyloides stercoralis is a parasite that lives in the gut of infected people. The infection is not serious for most people, but it can be fatal in people with immune deficiency. People become infected when they come in contact with soil or water contaminated with infectious worms. The chronic infection usually causes skin rash, vomiting, diarrhoea, and constipation, and respiratory problems, such as asthma-like illness. This disease may be treated with ivermectin or albendazole or thiabendazole. We wanted to know if ivermectin was better or worse than the other alternative therapies. What the research says We reviewed the evidence about the effect of ivermectin compared with albendazole and thiabendazole. After searching for relevant trials up to August 2015, we included seven randomized controlled trials, enrolling 1147 adults with chronic strongyloides infection, conducted between 1994 and 2011 in different locations (Africa, Southeast Asia, America, and Europe). Four trials assessed the effectiveness of ivermectin compared with albendazole and three trials assessed the effectiveness of ivermectin compared with thiabendazole. Comparison ivermectin versus albendazole Treatment with ivermectin probably cures more people than albendazole (moderate quality evidence), and may be equally or better tolerated (low quality evidence). The included trials did not report serious adverse events or death. Comparison ivermectin versus thiabendazole Treatment with ivermectin and thiabendazole may cure similar numbers of people with strongyloides infection (low quality evidence), but ivermectin is probably better tolerated (moderate quality evidence). The included trials did not report serious adverse events or death. PMID:26778150

Randomised controlled trials of veterinary homeopathy: characterising the peer-reviewed research literature for systematic review.

PubMed

Mathie, Robert T; Hacke, Daniela; Clausen, Jürgen

2012-10-01

Systematic review of the research evidence in veterinary homeopathy has never previously been carried out. This paper presents the search methods, together with categorised lists of retrieved records, that enable us to identify the literature that is acceptable for future systematic review of randomised controlled trials (RCTs) in veterinary homeopathy. All randomised and controlled trials of homeopathic intervention (prophylaxis and/or treatment of disease, in any species except man) were appraised according to pre-specified criteria. The following databases were systematically searched from their inception up to and including March 2011: AMED; Carstens-Stiftung Homeopathic Veterinary Clinical Research (HomVetCR) database; CINAHL; Cochrane Central Register of Controlled Trials; Embase; Hom-Inform; LILACS; PubMed; Science Citation Index; Scopus. One hundred and fifty records were retrieved; 38 satisfied the acceptance criteria (substantive report of a clinical treatment or prophylaxis trial in veterinary homeopathic medicine randomised and controlled and published in a peer-reviewed journal), and were thus eligible for future planned systematic review. Approximately half of the rejected records were theses. Seven species and 27 different species-specific medical conditions were represented in the 38 papers. Similar numbers of papers reported trials of treatment and prophylaxis (n=21 and n=17 respectively) and were controlled against placebo or other than placebo (n=18, n=20 respectively). Most research focused on non-individualised homeopathy (n=35 papers) compared with individualised homeopathy (n=3). The results provide a complete and clarified view of the RCT literature in veterinary homeopathy. We will systematically review the 38 substantive peer-reviewed journal articles under the main headings: treatment trials; prophylaxis trials. Copyright © 2012 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Effectiveness of an online social support intervention for caregivers of people with dementia: the study protocol of a randomised controlled trial.

PubMed

Dam, Alieske E H; de Vugt, Marjolein E; van Boxtel, Martin P J; Verhey, Frans R J

2017-08-29

Caregivers of people with dementia (PwD) face burden, feelings of loneliness, and social isolation. Previous studies have shown promising effects of online e-health interventions. Using social media may facilitate support for dementia caregiver networks. In an iterative step-wise approach, a social support tool entitled "Inlife" was developed. This paper describes the design of a study evaluating the effects of Inlife and its process characteristics. A mixed-method, randomised controlled trial with 122 caregivers of PwD will be conducted. Participants will be assigned to either the Inlife social support intervention or a waiting-list control group. After 16 weeks, the control group will obtain access to the Inlife environment. Data will be collected at baseline (T 0 ) and at 8-week (T 1 ), 16-week (T 2 ) and 42-week follow up (T 3 ). The 16-week follow-up assessment (T 2 ) is the primary endpoint to evaluate the results on the primary and secondary outcomes, measured by self-reported questionnaires. The primary outcomes include feelings of caregiver competence and perceived social support. The secondary outcomes include received support, feelings of loneliness, psychological complaints (e.g., anxiety, stress), and quality of life. A process evaluation, including semi-structured interviews, will be conducted to examine the internal and external validity of the intervention. Using a mixed-method design, our study will provide valuable insights into the usability, effectiveness, and factors related to implementation of the Inlife intervention. Our study results will indicate whether Inlife could be a valuable social support resource in future routine dementia care. Dutch trial register, NTR6131 . Registered on 20 October 2016.

Effects of advanced life support versus basic life support on the mortality rates of patients with trauma in prehospital settings: a study protocol for a systematic review and meta-analysis.

PubMed

Kondo, Yutaka; Fukuda, Tatsuma; Uchimido, Ryo; Hifumi, Toru; Hayashida, Kei

2017-10-22

Advanced life support (ALS) is thought to be associated with improved survival in prehospital trauma care when compared with basic life support (BLS). However, evidence on the benefits of prehospital ALS for patients with trauma is controversial. Therefore, we aim to clarify if ALS improves mortality in patients with trauma when compared with BLS by conducting a systematic review and meta-analysis of the recent literature. We will perform searches in PubMed, Embase and the Cochrane Central Register of Controlled Trials for published observational studies, controlled before-and-after studies, randomised controlled trials and other controlled trials conducted in humans and published until March 2017. We will screen search results, assess study selection, extract data and assess the risk of bias in duplicate; disagreements will be resolved through discussions. Data from clinically homogeneous studies will be pooled using a random-effects meta-analysis, heterogeneity of effects will be assessed using the χ 2 test of homogeneity, and any observed heterogeneity will be quantified using the I 2 statistic. Last, the Grading of Recommendations Assessment, Development and Evaluation approach will be used to rate the quality of the evidence. Our study does not require ethical approval as it is based on findings of previously published articles. Results will be disseminated through publication in a peer-reviewed journal, presentations at relevant conferences and publications for patient information. PROSPERO (International Prospective Register of Systematic Reviews) registration number CRD42017054389. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Dealing with daily challenges in dementia (deal-id study): effectiveness of the experience sampling method intervention 'Partner in Sight' for spousal caregivers of people with dementia: design of a randomized controlled trial.

PubMed

van Knippenberg, Rosalia J M; de Vugt, Marjolein E; Ponds, Rudolf W; Myin-Germeys, Inez; Verhey, Frans R J

2016-05-11

There is an urgent need for psychosocial interventions that effectively support dementia caregivers in daily life. The Experience Sampling Methodology (ESM) offers the possibility to provide a more dynamic view of caregiver functioning. ESM-derived feedback may help to redirect caregivers' behavior towards situations that elicit positive emotions and to increase their feelings of competence in the caretaking process. This paper presents the design of a study that evaluates the process characteristics and effects of the ESM-based intervention 'Partner in Sight'. A randomized controlled trial with 90 spousal caregivers of people with dementia will be conducted. Participants will be randomly assigned to the experimental (6-week ESM intervention including feedback), pseudo-experimental (6-week ESM intervention without feedback), or control group (care as usual). Assessments will be performed pre- and post-intervention and at 2-, and 6-month follow-up. Main outcomes will be sense of competence, perceived control, momentary positive affect, and psychological complaints (depressive symptoms, perceived stress, anxiety, momentary negative affect). In addition to the effect evaluation, a process and economic evaluation will be conducted to investigate the credibility and generalizability of the intervention, and its cost-effectiveness. The potential effects of the ESM intervention may help caregivers to endure their care responsibilities and prevent them from becoming overburdened. This is the first ESM intervention for caregivers of people with dementia. The results of this study, therefore, provide a valuable contribution to the growing knowledge on m-health interventions for dementia caregivers. Dutch Trial Register NTR4847 ; date registered Oct 9, 2014.

The effect of social franchising on access to and quality of health services in low- and middle-income countries.

PubMed

Koehlmoos, Tracey Perez; Gazi, Rukhsana; Hossain, S Shahed; Zaman, K

2009-01-21

Social franchising has developed as a possible means of improving provision of health services through engaging the non-state sector in low- and middle-income countries. To examine the evidence that social franchising has on access to and quality of health services in low- and middle-income countries. We searched the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register (up to October 2007), Cochrane Central Register of Controlled Trials (The Cochrane Library 2007, Issue 3), MEDLINE, Ovid (1950 to September Week 3 2007), EMBASE, Ovid (1980 to 2007 Week 38), CINAHL, Ovid (1982 to September Week 3 2007), EconLit, WebSPIRS (1969 to Sept 2007), LILACS, Science Citation Index Expanded and Social Sciences Citation Index (1975 to March 2008), Sociological Abstracts, CSA Illumnia (1952 September 2007), WHOLIS (1948 November 2007). Randomized controlled trials, non-randomized controlled trials, controlled before and after studies and interrupted time series comparing social franchising models with other models of health service delivery, other social franchising models or absence of health services. Two review authors independently applied the criteria for inclusion and exclusion of studies to scan titles and abstracts. The same two review authors independently screened full reports of selected citations . At each stage, results were compared and discrepancies settled through discussion. No studies were found which were eligible for inclusion in this review. There is a need to develop rigorous studies to evaluate the effects of social franchising on access to and quality of health services in low- and middle-income countries. Such studies should be informed by the wider literature to identify models of social franchising that have a sound theoretical basis and empirical research addressing their reach, acceptability, feasibility, maintenance and measurability.

Gene therapy for sickle cell disease.

PubMed

Olowoyeye, Abiola; Okwundu, Charles I

2016-11-14

Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review. The objectives of this review are:to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 15 August 2016. All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. No trials of gene therapy for sickle cell disease were found. No trials of gene therapy for sickle cell disease were reported. No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.

Gene therapy for sickle cell disease.

PubMed

Olowoyeye, Abiola; Okwundu, Charles I

2014-10-10

Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. The objectives of this review are:- to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;- to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 21 July 2014. All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. No trials of gene therapy for sickle cell disease were found. No trials of gene therapy for sickle cell disease were reported. No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.

Study protocol--metabolic syndrome, vitamin D and bone status in South Asian women living in Auckland, New Zealand: a randomised, placebo-controlled, double-blind vitamin D intervention.

PubMed

von Hurst, Pamela R; Stonehouse, Welma; Matthys, Christophe; Conlon, Cathryn; Kruger, Marlena C; Coad, Jane

2008-07-31

The identification of the vitamin D receptor in the endocrine pancreas suggests a role for vitamin D in insulin secretion. There is also some limited evidence that vitamin D influences insulin resistance, and thus the early stages of the development of type 2 diabetes. Eighty-four women of South Asian origin, living in Auckland, New Zealand, were randomised to receive either a supplement (4000IU 25(OH)D3 per day) or a placebo for 6 months. At baseline, all participants were vitamin D deficient (serum 25(OH)D3 <50 nmol/L), insulin resistant (HOMA-IR > 1.93) and/or hyperinsulinaemic, hyperglycemic or had clinical signs of dislipidaemia. Changes in HOMA-IR, lipids, parathyroid hormone, calcium and bone markers were monitored at 3 months and 6 months. This randomised, controlled trial will be the first to investigate the effect of vitamin D supplementation on insulin resistance in non-diabetic subjects. It will subsequently contribute to the growing body of evidence about the role of vitamin D in metabolic syndrome. Registered clinical. Registered clinical trial--Registration No. ACTRN12607000642482.

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Córdoba, Juan; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2015-02-25

Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index on 2 October 2014. We included randomised clinical trials, irrespective of the bias control, language, or publication status. The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous BCAA. The control groups received placebo/no intervention (two trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. Based on the combined Cochrane Hepato-Biliary Group score, we classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for-profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed-effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random-effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30). In this updated review, we included five additional trials. The analyses showed that BCAA had a beneficial effect on hepatic encephalopathy. We found no effect on mortality, quality of life, or nutritional parameters, but we need additional trials to evaluate these outcomes. Likewise, we need additional randomised clinical trials to determine the effect of BCAA compared with interventions such as non-absorbable disaccharides, rifaximin, or other antibiotics.

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2017-05-18

Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded and Conference Proceedings Citation Index - Science, and LILACS (May 2017). We included randomised clinical trials, irrespective of the bias control, language, or publication status. The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous BCAA. The control groups received placebo/no intervention (two trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. We classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for-profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed-effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random-effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30). In this updated review, we included five additional trials. The analyses showed that BCAA had a beneficial effect on hepatic encephalopathy. We found no effect on mortality, quality of life, or nutritional parameters, but we need additional trials to evaluate these outcomes. Likewise, we need additional randomised clinical trials to determine the effect of BCAA compared with interventions such as non-absorbable disaccharides, rifaximin, or other antibiotics.

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Córdoba, Juan; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2015-09-17

Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index (August 2015). We included randomised clinical trials, irrespective of the bias control, language, or publication status. The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous BCAA. The control groups received placebo/no intervention (two trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. We classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for-profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed-effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random-effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30). In this updated review, we included five additional trials. The analyses showed that BCAA had a beneficial effect on hepatic encephalopathy. We found no effect on mortality, quality of life, or nutritional parameters, but we need additional trials to evaluate these outcomes. Likewise, we need additional randomised clinical trials to determine the effect of BCAA compared with interventions such as non-absorbable disaccharides, rifaximin, or other antibiotics.

Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis.

PubMed

Mayo-Wilson, Evan; Imdad, Aamer; Herzer, Kurt; Yakoob, Mohammad Yawar; Bhutta, Zulfiqar A

2011-08-25

To determine if vitamin A supplementation is associated with reductions in mortality and morbidity in children aged 6 months to 5 years. Systematic review and meta-analysis. Two reviewers independently assessed studies for inclusion. Data were double extracted; discrepancies were resolved by discussion. Meta-analyses were performed for mortality, illness, vision, and side effects. Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Medline, Embase, Global Health, Latin American and Caribbean Health Sciences, metaRegister of Controlled Trials, and African Index Medicus. Databases were searched to April 2010 without restriction by language or publication status. Randomised trials of synthetic oral vitamin A supplements in children aged 6 months to 5 years. Studies of children with current illness (such as diarrhoea, measles, and HIV), studies of children in hospital, and studies of food fortification or β carotene were excluded. 43 trials with about 215,633 children were included. Seventeen trials including 194,483 participants reported a 24% reduction in all cause mortality (rate ratio=0.76, 95% confidence interval 0.69 to 0.83). Seven trials reported a 28% reduction in mortality associated with diarrhoea (0.72, 0.57 to 0.91). Vitamin A supplementation was associated with a reduced incidence of diarrhoea (0.85, 0.82 to 0.87) and measles (0.50, 0.37 to 0.67) and a reduced prevalence of vision problems, including night blindness (0.32, 0.21 to 0.50) and xerophthalmia (0.31, 0.22 to 0.45). Three trials reported an increased risk of vomiting within the first 48 hours of supplementation (2.75, 1.81 to 4.19). Vitamin A supplementation is associated with large reductions in mortality, morbidity, and vision problems in a range of settings, and these results cannot be explained by bias. Further placebo controlled trials of vitamin A supplementation in children between 6 and 59 months of age are not required. However, there is a need for further studies comparing different doses and delivery mechanisms (for example, fortification). Until other sources are available, vitamin A supplements should be given to all children at risk of deficiency, particularly in low and middle income countries.

Pharmacotherapy for trichotillomania.

PubMed

Rothbart, Rachel; Amos, Taryn; Siegfried, Nandi; Ipser, Jonathan C; Fineberg, Naomi; Chamberlain, Samuel R; Stein, Dan J

2013-11-08

Trichotillomania (TTM) (hair-pulling disorder) is a prevalent and disabling disorder characterised by recurrent hair-pulling. The effect of medication on trichotillomania has not been systematically evaluated. To assess the effects of medication for trichotillomania in adults compared with placebo or other active agents. We searched the Cochrane Central Register of Controlled Trials and the Cochrane Depression, Anxiety and Neurosis Group Register (to 31 July 2013), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years); EMBASE (1974 to date); MEDLINE (1950 to date) and PsycINFO (1967 to date). Two review authors identified relevant trials by assessing the abstracts of all possible studies. We selected randomised controlled trials (RCTs) of a medication versus placebo or active agent for TTM in adults. Two review authors independently performed the data extraction and 'Risk of bias' assessments, and disagreements were resolved through discussion with a third review author. Primary outcomes included the mean difference (MD) in reduction of trichotillomania symptoms on a continuous measure of trichotillomania symptom severity, and the risk ratio (RR) of the clinical response based on a dichotomous measure, with 95% confidence intervals (CIs). We identified eight studies with a total of 204 participants and a mean sample size of 25. All trials were single-centre trials, and participants seen on an outpatient basis. Seven studies compared medication and placebo (n = 184); one study compared medication and another active agent (n = 13). Duration of the studies was six to twelve weeks. Meta-analysis was not undertaken because of the methodological heterogeneity of the trials. The studies did not employ intention-to-treat analyses and were at a high risk of attrition bias. Adverse events were not well-documented in the studies.None of the three studies of selective serotonin reuptake inhibitors (SSRIs) demonstrated strong evidence of a treatment effect on any of the outcomes of interest. The unpublished naltrexone study did not provide strong evidence of a treatment effect. Two studies, an olanzapine study and a N-acetylcysteine (NAC) study, reported statistically significant treatment effects. One study of clomipramine demonstrated a treatment effect on two out of three measures of response to treatment. No particular medication class definitively demonstrates efficacy in the treatment of trichotillomania. Preliminary evidence suggests treatment effects of clomipramine, NAC and olanzapine based on three individual trials, albeit with very small sample sizes.

Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

PubMed

Elphick, Heather E; Southern, Kevin W

2014-11-28

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, their many side effects are well-documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis:1. improve clinical status compared to placebo or standard therapy (no placebo);2. do not have unacceptable adverse effects.If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.In addition, pharmaceutical companies were approached.Date of the most recent search of the Group's Trials Register: 17 March 2014. Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis. Four trials were identified by the searches; none of which was judged eligible for inclusion in the review. No completed randomised controlled trials were included. At present, there are no randomised controlled trials to evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although trials in people who do not have cystic fibrosis have shown clinical and serological evidence of improvement and a reduction in the use of corticosteroids with no increase in adverse effects. Trials with clear outcome measures are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

PubMed

Elphick, Heather E; Southern, Kevin W

2016-11-08

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, their many side effects are well-documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review. The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis:1. improve clinical status compared to placebo or standard therapy (no placebo);2. do not have unacceptable adverse effects.If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.In addition, pharmaceutical companies were approached.Date of the most recent search of the Group's Trials Register: 29 September 2016. Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis. Four trials were identified by the searches; none of which was judged eligible for inclusion in the review. No completed randomised controlled trials were included. At present, there are no randomised controlled trials to evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although trials in people who do not have cystic fibrosis have shown clinical and serological evidence of improvement and a reduction in the use of corticosteroids with no increase in adverse effects. Trials with clear outcome measures are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis

PubMed Central

Mayo-Wilson, Evan; Imdad, Aamer; Herzer, Kurt; Yakoob, Mohammad Yawar

2011-01-01

Objective To determine if vitamin A supplementation is associated with reductions in mortality and morbidity in children aged 6 months to 5 years. Design Systematic review and meta-analysis. Two reviewers independently assessed studies for inclusion. Data were double extracted; discrepancies were resolved by discussion. Meta-analyses were performed for mortality, illness, vision, and side effects. Data sources Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Medline, Embase, Global Health, Latin American and Caribbean Health Sciences, metaRegister of Controlled Trials, and African Index Medicus. Databases were searched to April 2010 without restriction by language or publication status. Eligibility criteria for selecting studies Randomised trials of synthetic oral vitamin A supplements in children aged 6 months to 5 years. Studies of children with current illness (such as diarrhoea, measles, and HIV), studies of children in hospital, and studies of food fortification or β carotene were excluded. Results 43 trials with about 215 633 children were included. Seventeen trials including 194 483 participants reported a 24% reduction in all cause mortality (rate ratio=0.76, 95% confidence interval 0.69 to 0.83). Seven trials reported a 28% reduction in mortality associated with diarrhoea (0.72, 0.57 to 0.91). Vitamin A supplementation was associated with a reduced incidence of diarrhoea (0.85, 0.82 to 0.87) and measles (0.50, 0.37 to 0.67) and a reduced prevalence of vision problems, including night blindness (0.32, 0.21 to 0.50) and xerophthalmia (0.31, 0.22 to 0.45). Three trials reported an increased risk of vomiting within the first 48 hours of supplementation (2.75, 1.81 to 4.19). Conclusions Vitamin A supplementation is associated with large reductions in mortality, morbidity, and vision problems in a range of settings, and these results cannot be explained by bias. Further placebo controlled trials of vitamin A supplementation in children between 6 and 59 months of age are not required. However, there is a need for further studies comparing different doses and delivery mechanisms (for example, fortification). Until other sources are available, vitamin A supplements should be given to all children at risk of deficiency, particularly in low and middle income countries. PMID:21868478

Lateral Wedge Insoles as a Conservative Treatment for Pain in Patients With Medial Knee Osteoarthritis

PubMed Central

Parkes, Matthew J.; Maricar, Nasimah; Lunt, Mark; LaValley, Michael P.; Jones, Richard K.; Segal, Neil A.; Takahashi-Narita, Kayoko; Felson, David T.

2015-01-01

IMPORTANCE There is no consensus regarding the efficacy of lateral wedge insoles as a treatment for pain in medial knee osteoarthritis. OBJECTIVE To evaluate whether lateral wedge insoles reduce pain in patients with medial knee osteoarthritis compared with an appropriate control. DATA SOURCES Databases searched include the Cochrane Central Register of Controlled Trials, EMBASE, AMED, MEDLINE, CINAHL Plus, ScienceDirect, SCOPUS, Web of Science, and BIOSIS from inception to May 2013, with no limits on study date or language. The metaRegister of Controlled Trials and the NHS Evidence website were also searched. STUDY SELECTION Included were randomized trials comparing shoe-based treatments (lateral heel wedge insoles or shoes with variable stiffness soles) aimed at reducing medial knee load, with a neutral or no wedge control condition in patients with painful medial knee osteoarthritis. Studies must have included patient-reported pain as an outcome. DATA EXTRACTION AND SYNTHESIS Trial data were extracted independently by 2 researchers using a standardized form. Risk of bias was assessed using the Cochrane Risk of Bias tool by 2 observers. Eligible studies were pooled using a random-effects approach. MAIN OUTCOME AND MEASURES Change in self-reported knee pain at follow-up. RESULTS Twelve trials met inclusion criteria with a total of 885 participants of whom 502 received lateral wedge treatment. The pooled standardized mean difference (SMD) suggested a favorable association with lateral wedges compared with control (SMD, −0.47; 95% CI, −0.80 to −0.14); however, substantial heterogeneity was present (I2 = 82.7%). This effect size represents an effect of −2.12 points on the 20-point Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scale. Larger trials with a lower risk of bias suggested a null association. Meta-regression analyses showed that higher effect sizes (unstandardized β, 1.07 [95% CI, 0.28 to 1.87] for trials using a no treatment control) were seen in trials using a no wedge treatment control group (n = 4 trials; SMD, −1.20 [95% CI, −2.09 to −0.30]) and lower effect sizes (unstandardized β, 0.26 [95% CI, 0.002 to 0.52] for each bias category deemed low risk) when the study method was deemed at low risk of bias. Among trials in which the control treatment was a neutral insole (n = 7), lateral wedges showed no association (SMD, −0.03 [95% CI, −0.18 to 0.12] on WOMAC; this represents an effect of −0.12 points), and results showed little heterogeneity (I2 = 7.1%). CONCLUSIONS AND RELEVANCE Although meta-analytic pooling of all studies showed a statistically significant association between use of lateral wedges and lower pain in medial knee osteoarthritis, restriction of studies to those using a neutral insole comparator did not show a significant or clinically important association. These findings do not support the use of lateral wedges for this indication. PMID:23989797

Efficacy of Platelet-Rich Fibrin After Mandibular Third Molar Extraction: A Systematic Review and Meta-Analysis.

PubMed

Al-Hamed, Faez Saleh; Tawfik, Mohamed Abdel-Monem; Abdelfadil, Ehab; Al-Saleh, Mohammed A Q

2017-06-01

To assess the effect of platelet-rich fibrin (PRF) on the healing process of the alveolar socket after surgical extraction of the mandibular third molars. PubMed, the Cochrane Central Register of Controlled Trials, Scopus, and relevant journals were searched using a combination of specific keywords ("platelet-rich fibrin," "oral surgery," and "third molar"). The final search was conducted on November 2, 2015. Randomized controlled clinical trials, as well as controlled clinical trials, aimed at comparing the effect of PRF versus natural healing after extraction of mandibular third molars were included. Five randomized controlled trials and one controlled clinical trial were included. There were 335 extractions (168 with PRF and 167 controls) in 183 participants. Considerable heterogeneity in study characteristics, outcome variables, and estimated scales was observed. Positive results were generally recorded for pain, trismus, swelling, periodontal pocket depth, soft tissue healing, and incidence of localized osteitis, but not in all studies. However, no meta-analysis could be conducted for such variables because of the different measurement scales used. The qualitative and meta-analysis results showed no significant improvement in bone healing with PRF-treated sockets compared with the naturally healing sockets. Within the limitations of the available evidence, PRF seems to have no beneficial role in bone healing after extraction of the mandibular third molars. Future standardized randomized controlled clinical trials are required to estimate the effect of PRF on socket regeneration. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

The effect of static scanning and mobility training on mobility in people with hemianopia after stroke: A randomized controlled trial comparing standardized versus non-standardized treatment protocols

PubMed Central

2011-01-01

Background Visual loss following stroke impacts significantly on activities of daily living and is an independent risk factor for becoming dependent. Routinely, allied health clinicians provide training for visual field loss, mainly with eye movement based therapy. The effectiveness of the compensatory approach to rehabilitation remains inconclusive largely due to difficulty in validating functional outcome with the varied type and dosage of therapy received by an individual patient. This study aims to determine which treatment is more effective, a standardized approach or individualized therapy in patients with homonymous hemianopia post stroke. Methods/Design This study is a double-blind randomized controlled, multicenter trial. A standardised scanning rehabilitation program (Neuro Vision Technology (NVT) program) of 7 weeks at 3 times per week, is compared to individualized therapy recommended by clinicians. Discussion The results of the trial will provide information that could potentially inform the allocation of resources in visual rehabilitation post stroke. Trial Registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000494033 PMID:21767413

The effectiveness of a skin care program for the prevention of contact dermatitis in health care workers (the Healthy Hands Project): study protocol for a cluster randomized controlled trial.

PubMed

Soltanipoor, Maryam; Kezic, Sanja; Sluiter, Judith K; Rustemeyer, Thomas

2017-02-28

Health care workers (HCW) are at high risk for developing occupational hand dermatitis (HD) due to frequent exposure to 'wet work'. Amongst HCWs, nurses are at highest risk, with an estimated point prevalence of HD ranging between 12 and 30%. The burden of disease is high with chronicity, sick leave, risk of unemployment and impaired quality of life. Despite evidence from the medical literature on the risk factors and the importance of skin care in the prevention of HD, in practice, compliance to skin care protocols are below 30%. New preventive strategies are obviously needed. This is a cluster randomized controlled trial, focusing on nurses performing wet work. In total, 20 wards are recruited to include 504 participating nurses in the study at baseline. The wards will be randomized to an intervention or a control group and followed up for 18 months. The intervention consists of the facilitation of creams being available at the wards combined with the continuous electronic monitoring of their consumption with regular feedback on skin care performance in teams of HCWs. Both the intervention and the control group receive basic education on skin protection (as 'care as usual'). Every 6 months, participants of both groups will fill in the questionnaires regarding exposure to wet work and skin protective behavior. Furthermore, skin condition will be assessed and samples of the stratum corneum collected. The effect of the intervention will be measured by comparing the change in Hand Eczema Severity Index (HECSI score) from baseline to 12 months. The Natural Moisturizing Factor (NMF) levels, measured in the stratum corneum as an early biomarker of skin barrier damage, and the total consumption of creams per ward will be assessed as a secondary outcome. This trial will assess the clinical effectiveness of an intervention program to prevent hand dermatitis among health care workers TRIAL REGISTRATION: Netherlands Trial Register (NTR), identification number NTR5564 . Registered on 2 November 2015.

Impact of registration on clinical trials on infection risk in pediatric acute myeloid leukemia.

PubMed

Dix, David; Aplenc, Richard; Bowes, Lynette; Cellot, Sonia; Ethier, Marie-Chantal; Feusner, Jim; Gillmeister, Biljana; Johnston, Donna L; Lewis, Victor; Michon, Bruno; Mitchell, David; Portwine, Carol; Price, Victoria; Silva, Mariana; Stobart, Kent; Yanofsky, Rochelle; Zelcer, Shayna; Beyene, Joseph; Sung, Lillian

2016-04-01

Little is known about the impact of enrollment on therapeutic clinical trials on adverse event rates. Primary objective was to describe the impact of clinical trial registration on sterile site microbiologically documented infection for children with newly diagnosed acute myeloid leukemia (AML). We conducted a multicenter cohort study that included children aged ≤18 years with de novo AML. Primary outcome was microbiologically documented sterile site infection. Infection rates were compared between those registered and not registered on clinical trials. Five hundred seventy-four children with AML were included of which 198 (34.5%) were registered on a therapeutic clinical trial. Overall, 400 (69.7%) had at least one sterile site microbiologically documented infection. In multiple regression, registration on clinical trials was independently associated with a higher risk of microbiologically documented sterile site infection [adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 1.01-1.53; p = 0.040] and viridans group streptococcal infection (OR 1.46, 95% CI 1.08-1.98; p = 0.015). Registration on trials was not associated with Gram-negative or invasive fungal infections. Children with newly diagnosed AML enrolled on clinical trials have a higher risk of microbiologically documented sterile site infection. This information may impact on supportive care practices in pediatric AML. © 2015 UICC.

Surgical and nonsurgical interventions for vulvar and clitoral pain in girls and women living with female genital mutilation: A systematic review.

PubMed

Ezebialu, Ifeanyichukwu; Okafo, Obiamaka; Oringanje, Chukwudi; Ogbonna, Udoezuo; Udoh, Ekong; Odey, Friday; Meremikwu, Martin M

2017-02-01

Vulvar and clitoral pain are known complications of female genital mutilation (FGM). Several interventions have been used to treat these conditions. This review focuses on surgical and nonsurgical interventions to improve vulvar and clitoral pain in women living with FGM. To evaluate the impact of nonsurgical and surgical interventions for alleviating vulvar and clitoral pain in women living with any type of FGM and to assess the associated adverse events. The search included the following major databases: Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov. These were searched from inception until August 10, 2015 without any language restrictions. Study designs included randomized controlled trials, cluster randomized trials, nonrandomized trials, cohort studies, case-control studies, controlled before-and-after studies, historical control studies, and interrupted time series with reported data comparing outcomes among women with FGM who were treated for clitoral or vulvar pain with either surgical or nonsurgical interventions. Two team members independently screened studies for eligibility. No studies were included. Limited information exists on management of vulvar and clitoral pain in women living with FGM. This constitutes an important area for further research. CRD42015024521. © 2017 International Federation of Gynecology and Obstetrics.The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

Ginkgo biloba extract for age-related macular degeneration.

PubMed

Evans, Jennifer R

2013-01-31

Ginkgo is used in the treatment of peripheral vascular disease and 'cerebral insufficiency'. It is thought to have several potential mechanisms of action including increased blood flow, platelet activating factor antagonism, and prevention of membrane damage caused by free radicals. Vascular factors and oxidative damage are thought to be two potential mechanisms in the pathology of age-related macular degeneration (AMD). The objective of this review was to determine the effect of Ginkgo biloba extract on the progression of AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2012), EMBASE (January 1980 to October 2012), Allied and Complementary Medicine Database (AMED) (January 1985 to October 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 October 2012. We searched the reference lists of identified reports and the Science Citation Index. We also contacted investigators of included studies for additional information. All randomised trials in people with AMD where Ginkgo biloba extract had been compared to control were included. The review author extracted data using a standardised form. The data were verified with the trial investigators. Trial quality was assessed. Two published trials were identified that randomised a total of 119 people. In one study conducted in France, 20 people were randomly allocated to Gingko biloba extract EGb 761 80 mg twice daily or placebo. In the other study conducted in Germany, 99 people were randomly allocated to two different doses of Ginkgo biloba extract EGb 761 (240 mg per day and 60 mg per day). Treatment duration in both studies was six months. Both trials reported some positive effects of Ginkgo biloba on vision however their results could not be pooled. Adverse effects and quality of life for people with AMD were not reported. The question as to whether people with AMD should take Ginkgo biloba extract to prevent progression of the disease has not been answered by research to date. Two small trials have suggested possible benefit of Gingko biloba on vision and further trials are warranted. Ginkgo biloba is widely used in China, Germany, and France. Future trials should be larger, and last longer, in order to provide a more robust measure of the effect of Gingko biloba extract on AMD.

A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3 Trial Intracranial Bleeding Mechanistic Sub-Study [CRASH-3 IBMS]).

PubMed

Mahmood, Abda; Roberts, Ian; Shakur, Haleema

2017-07-17

Tranexamic acid prevents blood clots from breaking down and reduces bleeding. However, it is uncertain whether tranexamic acid is effective in traumatic brain injury. The CRASH-3 trial is a randomised controlled trial that will examine the effect of tranexamic acid (versus placebo) on death and disability in 13,000 patients with traumatic brain injury. The CRASH-3 trial hypothesizes that tranexamic acid will reduce intracranial haemorrhage, which will reduce the risk of death. Although it is possible that tranexamic acid will reduce intracranial bleeding, there is also a potential for harm. In particular, tranexamic acid may increase the risk of cerebral thrombosis and ischaemia. The protocol detailed here is for a mechanistic sub-study nested within the CRASH-3 trial. This mechanistic sub-study aims to examine the effect of tranexamic acid (versus placebo) on intracranial bleeding and cerebral ischaemia. The CRASH-3 Intracranial Bleeding Mechanistic Sub-Study (CRASH-3 IBMS) is nested within a prospective, double-blind, multi-centre, parallel-arm randomised trial called the CRASH-3 trial. The CRASH-3 IBMS will be conducted in a cohort of approximately 1000 isolated traumatic brain injury patients enrolled in the CRASH-3 trial. In the CRASH-3 IBMS, brain scans acquired before and after randomisation are examined, using validated methods, for evidence of intracranial bleeding and cerebral ischaemia. The primary outcome is the total volume of intracranial bleeding measured on computed tomography after randomisation, adjusting for baseline bleeding volume. Secondary outcomes include progression of intracranial haemorrhage (from pre- to post-randomisation scans), new intracranial haemorrhage (seen on post- but not pre-randomisation scans), intracranial haemorrhage following neurosurgery, and new focal ischaemic lesions (seen on post-but not pre-randomisation scans). A linear regression model will examine whether receipt of the trial treatment can predict haemorrhage volume. Bleeding volumes and new ischaemic lesions will be compared across treatment groups using relative risks and 95% confidence intervals. The CRASH-3 IBMS will provide an insight into the mechanism of action of tranexamic acid in traumatic brain injury, as well as information about the risks and benefits. Evidence from this trial could inform the management of patients with traumatic brain injury. The CRASH-3 trial was prospectively registered and the CRASH-3 IBMS is an addition to the original protocol registered at the International Standard Randomised Controlled Trials registry ( ISRCTN15088122 ) 19 July 2011, and ClinicalTrials.gov on 25 July 2011 (NCT01402882).

Robot-assisted single-site compared with laparoscopic single-incision cholecystectomy for benign gallbladder disease: protocol for a randomized controlled trial.

PubMed

Grochola, Lukasz Filip; Soll, Christopher; Zehnder, Adrian; Wyss, Roland; Herzog, Pascal; Breitenstein, Stefan

2017-02-09

Recent advances in robotic technology suggest that the utilization of the da Vinci Single-Site™ platform for cholecystectomy is safe, feasible and results in a shorter learning curve compared to conventional single-incision laparoscopic cholecystectomy. Moreover, the robot-assisted technology has been shown to reduce the surgeon's stress load compared to standard single-incision laparoscopy in an experimental setup, suggesting an important advantage of the da Vinci platform. However, the above-mentioned observations are based solely on case series, case reports and experimental data, as high-quality clinical trials to demonstrate the benefits of the da Vinci Single-Site™ cholecystectomy have not been performed to date. This study addresses the question whether robot-assisted Single-Site™ cholecystectomy provides significant benefits over single-incision laparoscopic cholecystectomy in terms of surgeon's stress load, while matching the standards of the conventional single-incision approach with regard to peri- and postoperative outcomes. It is designed as a single centre, single-blinded randomized controlled trial, which compares both surgical approaches with the primary endpoint surgeon's physical and mental stress load at the time of surgery. In addition, the study aims to assess secondary endpoints such as operating time, conversion rates, additional trocar placement, intra-operative blood loss, length of hospital stay, costs of procedure, health-related quality of life, cosmesis and complications. Patients as well as ward staff are blinded until the 1 st postoperative year. Sample size calculation based on the results of a previously published experimental setup utilizing an estimated effect size of surgeon's comfort of 0.8 (power of 0.8, alpha-error level of 0.05, error margin of 10-15%) resulted in a number of 30 randomized patients per arm. The study is the first randomized controlled trial that compares the da Vinci Single Site™ platform to conventional laparoscopic approaches in cholecystectomy, one of the most frequently performed operations in general surgery. This trial is registered at clinicaltrials.gov (trial number: NCT02485392 ). Registered February 19, 2015.

Comprehensive geriatric assessment for older adults admitted to hospital: meta-analysis of randomised controlled trials.

PubMed

Ellis, Graham; Whitehead, Martin A; Robinson, David; O'Neill, Desmond; Langhorne, Peter

2011-10-27

To evaluate the effectiveness of comprehensive geriatric assessment in hospital for older adults admitted as an emergency. We searched the EPOC Register, Cochrane's Controlled Trials Register, the Database of Abstracts of Reviews of Effects (DARE), Medline, Embase, CINAHL, AARP Ageline, and handsearched high yield journals. Randomised controlled trials of comprehensive geriatric assessment (whether by mobile teams or in designated wards) compared with usual care. Comprehensive geriatric assessment is a multidimensional interdisciplinary diagnostic process used to determine the medical, psychological, and functional capabilities of a frail elderly person to develop a coordinated and integrated plan for treatment and long term follow-up. Three independent reviewers assessed eligibility and trial quality and extracted published data. Two additional reviewers moderated. Twenty two trials evaluating 10,315 participants in six countries were identified. For the primary outcome "living at home," patients who underwent comprehensive geriatric assessment were more likely to be alive and in their own homes at the end of scheduled follow-up (odds ratio 1.16 (95% confidence interval 1.05 to 1.28; P = 0.003; number needed to treat 33) at a median follow-up of 12 months versus 1.25 (1.11 to 1.42; P < 0.001; number needed to treat 17) at a median follow-up of six months) compared with patients who received general medical care. In addition, patients were less likely to be living in residential care (0.78, 0.69 to 0.88; P < 0.001). Subgroup interaction suggested differences between the subgroups "wards" and "teams" in favour of wards. Patients were also less likely to die or experience deterioration (0.76, 0.64 to 0.90; P = 0.001) and were more likely to experience improved cognition (standardised mean difference 0.08, 0.01 to 0.15; P = 0.02) in the comprehensive geriatric assessment group. Comprehensive geriatric assessment increases patients' likelihood of being alive and in their own homes after an emergency admission to hospital. This seems to be especially true for trials of wards designated for comprehensive geriatric assessment and is associated with a potential cost reduction compared with general medical care.

Can a documentary increase help-seeking intentions in men? A randomised controlled trial.

PubMed

King, Kylie Elizabeth; Schlichthorst, Marisa; Spittal, Matthew J; Phelps, Andrea; Pirkis, Jane

2018-01-01

We investigated whether a public health intervention-a three-part documentary called Man Up which explored the relationship between masculinity and mental health, well-being and suicidality-could increase men's intentions to seek help for personal and emotional problems. We recruited men aged 18 years or over who were not at risk of suicide to participate in a double-blind randomised controlled trial. Participants were randomly assigned (1:1) via computer randomisation to view Man Up (the intervention) or a control documentary. We hypothesised that 4 weeks after viewing Man Up participants would report higher levels of intention to seek help than those who viewed the control documentary. Our primary outcome was assessed using the General Help Seeking Questionnaire, and was analysed for all participants. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616001169437, Universal Trial Number: U1111-1186-1459) and was funded by the Movember Foundation. Three hundred and fifty-four men were assessed for eligibility for the trial and randomised to view Man Up or the control documentary. Of these, 337 completed all stages (nine participants were lost to follow-up in the intervention group and eight in the control group). Linear regression analysis showed a significant increase in intentions to seek help in the intervention group, but not in the control group (coef.=2.06, 95% CI 0.48 to 3.63, P=0.01). Our trial demonstrates the potential for men's health outcomes to be positively impacted by novel, media-based public health interventions that focus on traditional masculinity. ACTRN12616001169437, Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial

PubMed Central

2011-01-01

Background Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. Methods/Design The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis. Discussion This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants. Trial registration number Netherlands Trial Register (NTR): NTR2768 PMID:22070744

Improving Well-being and Health for People with Dementia (WHELD): study protocol for a randomised controlled trial

PubMed Central

2014-01-01

Background People with dementia living in care homes often have complex mental health problems, disabilities and social needs. Providing more comprehensive training for staff working in care home environments is a high national priority. It is important that this training is evidence based and delivers improvement for people with dementia residing in these environments. Well-being and Health for People with Dementia (WHELD) combines the most effective elements of existing approaches to develop a comprehensive but practical staff training intervention. This optimised intervention is based on a factorial study and qualitative evaluation, to combine: training on person-centred care, promoting person-centred activities and interactions, and providing care home staff and general practitioners with updated knowledge regarding the optimal use of psychotropic medications for persons with dementia in care homes. Design The trial will be a randomised controlled two-arm cluster single blind trial that will take place for nine months across 80 care homes in the United Kingdom. Discussion The overarching goal of this trial is to determine whether this optimised WHELD intervention is more effective in improving the quality of life and mental health than the usual care provided to people with dementia living in nursing homes. This study will be the largest and best powered randomised controlled trial (RCT) evaluating the benefits of an augmented person-centred care training intervention in care homes worldwide. Trial registration Current controlled trials ISRCTN62237498 Date registered: 5 September 2013 PMID:25016303

Effect of Hibiscus sabdariffa Calices on Dyslipidemia in Obese Adolescents: A Triple-masked Randomized Controlled Trial

PubMed Central

Sabzghabaee, Ali Mohammad; Ataei, Ehsan; Kelishadi, Roya; Ghannadi, Alireza; Soltani, Rasool; Badri, Shirinsadat; Shirani, Shahin

2013-01-01

Conflict of interest: none declared. Objective We aimed to evaluate the effects of Hibiscus sabdariffa (HS) calices on controlling dyslipidemia in obese adolescents. Methodology In this triple blind randomized placebo-controlled clinical trial which was registered in the Iranian registry for clinical trials (IRCT201109122306N2), 90 obese adolescents aged 12-18 years with documented dyslipidemia were randomly assigned in two groups of cases who received 2 grams of fine powdered calices of Hibiscus sabdariffa per day for one month and controls who received placebo powder with the same dietary and physical activity recommendations and duration of exposure. Full lipid profile and fasting blood sugar measured before and after the trial. Data were analyzed using multivariate general linear model. Findings Overall, 72 participants (mean age of 14.21±1.6, 35 boys) completed the trial. The two arms of the study (cases and controls) were not statistically different in terms of age, gender, weight, body mass index (BMI) and lipid profile before the trial. Serum total cholesterol, low density lipoprotein cholesterol and serum triglyceride showed a significant decrease in cases group but high density lipoprotein cholesterol level was not changed significantly. Conclusion It is concluded that Hibiscus sabdariffa calyces powder may have significant positive effects on lipid profile of adolescents which maybe attributed to its polyphenolic and antioxidant content. Further studies are needed on dose-response and formulation optimization. PMID:24082826

Efficacy of different fungicides against Rhizoctonia brown patch and Pythium blight on turfgrass in Italy.

PubMed

Mocioni, M; Titone, P; Garibaldi, A; Gullino, M L

2003-01-01

Brown patch, incited by Rhizoctonia solani Kuhn, and Pythium blight, caused by Pythium spp. are two of the diseases most frequently observed on turfgrass in high maintenance stands, as on golf courses. In such conditions the control strategies, based on chemicals, are particularly difficult due to the scarcity of fungicides registered for turf in Italy. The results obtained in experimental trials carried out to evaluate the efficacy of chemical and biological products against brown patch and Pythium blight are reported. On mature turfgrass, maintained under fairway conditions, azoxystrobin, and trifoxystrobin, not yet registered on turf, were very effective against brown patch. Tebuconazole, applied in three different formulations, was very effective against R. solani, while Trichoderma spp. and azadiractine did not control the pathogen. In greenhouse conditions on Agrostis stolonifera, in the presence of severe disease incidence, due to artificial inoculation, benalaxyl-M satisfactorily controlled Pythium blight; Trichoderma spp. as well as a commercial formulation of T. harzianum, applied one week before the inoculation, were not effective. Among the fungicides not yet registered for use on turfgrass in Italy, metalaxyl-M + mancozeb was effective against Pythium blight.

Safety and efficacy of colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia as part of a macro-project funded by the Seventh Framework Program of the European Commission studying off-patent antibiotics: study protocol for a randomized controlled trial.

PubMed

Rosso-Fernández, Clara; Garnacho-Montero, José; Antonelli, Massimo; Dimopoulos, George; Cisneros, José Miguel

2015-03-20

Ventilator-associated pneumonia (VAP) is one of the most common and severe hospital-adquired infections, and multidrugresistant gram-negative bacilli (MDR-GNB) constitute the main etiology in many countries. Inappropriate empiric antimicrobial treatment is associated with increased mortality. In this context, the empirical treatment of choice for VAP is unknown. Colistin, is now the antimicrobial with greatest in vitro activity against MDR-GNB. The MagicBullet clinical trial is an investigator-driven clinical study, funded by the Seventh Framework Program of the European Commission. This is designed as a phase IV, randomized, controlled, open label, non-inferiority and international trial to assess the safety and efficacy of colistin versus meropenem in late onset VAP. The study is conducted in a total of 32 centers in three European countries (Spain, Italy and Greece) with specific high incidences of infections caused by MDR-GNB. Patients older than 18 years who develop VAP with both clinical and radiological signs, and are on mechanical ventilation for more than 96 hours, or less than 96 hours but with previous antibiotic treatment plus one week of hospitalization, are candidates for inclusion in the study. A total sample size of 496 patients will be randomized according to a severity clinical score (at the time of VAP diagnosis in a 1:1 ratio to receive either colistin 4.5 MU as a loading dose, followed by 3 MU every eight hours (experimental arm), or meropenem 2 g every eight hours (control arm), both combined with levofloxacin. Mortality from any cause at 28 days will be considered as the main outcome. Clinical and microbiological cure will be evaluated at 72 hours, eight days, the finalization of antibiotic treatment, and 28 days of follow-up. The efficacy evaluation will be performed in every patient who receives at least one study treatment drug, and with etiologic diagnosis of VAP, intention-to-treat population and per protocol analysis will be performed. Currently, there is no study being undertaken which analyzes empiric treatment of (VAP) with a suspicion of multi-resistance. Colistin, an off-patent antibiotic commercialized for more than 60 years, could widen the antibiotic alternatives for a high-mortality illness aggravated by antibiotic resistance. This trial is registered with ClinicalTrials.gov (identifier: NCT01292031 ; registered on 29 June 2012) and EudraCT (identifier: 2010-023310-31; registered on 7 February 2011).

Short versus long duration infusions of paclitaxel for any advanced adenocarcinoma

PubMed Central

Williams, Chris; Bryant, Andrew

2014-01-01

Background Paclitaxel has become a standard drug used in a number of common cancers. At first long infusions were used to reduce the rate of inflow of the drug and as a result reduce the occurrence of hypersensitivity types of allergic reactions. Trials with shorter durations of infusion, and using a cocktail of anti-allergic drugs to prevent hypersensitivity reactions, some randomised, were begun. These were interpreted as showing that effectiveness of treatment was not lessened by a short infusion time. These studies also appeared to show that some important toxicities were less common with short infusions and that they were more convenient for the patient and the hospital. Objectives To assess the effectiveness and toxicity of short versus long infusions of paclitaxel for any advanced adenocarcinoma. Search methods We searched the Cochrane Gynaecological Cancer Review Group Specialised Register, The Cochrane Central Register of Controlled Trials (CENTRAL) Issue 1, 2009, MEDLINE and EMBASE up to March 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included trials and contacted experts in the field, as well as drug companies. Selection criteria The review was restricted to randomised controlled trials (RCTs) of single agent paclitaxel or paclitaxel with other drugs, where the only variable was the duration of paclitaxel infusion. The review only includes patients with advanced adenocarcinoma. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in meta-analyses. Main results We identified six trials that met our inclusion criteria. The trials compared 3, 24 and 96 hour infusions and one trial examined different schedules (1 versus 3 day). From the included RCTs we found no evidence of a difference between short and long infusions in terms of overall and progression-free survival and tumour non-response. In most cases a greater proportion of adverse events and severe toxicity occurred in the 24 hour infusion group compared to the 3 hour group with many of the analyses being highly statistically significant (RR = 0.32, 95% CI 0.22, 0.47, RR = 0.06, 95% CI 0.02, 0.17, RR = 0.59, 95% CI 0.40, 0.88, RR = 0.52, 95% CI 0.28, 0.97 for severe hypersensitivity, febrile neutropenia, sore mouth and diarrhoea outcomes respectively). Although a meta analysis of three trials found that 3 hour infusions were associated with a statistically significant increase in the risk of neurosensory changes compared with 24 hour infusions (RR = 1.26, 95% CI 1.09 to 1.46). Adverses events were not comprehensively reported for any of the other comparisons. Outcomes were incompletely documented and QoL outcomes were not reported in any of the trials. The strength of the evidence is weak in this review as it is based on meta analyses of very few trials or single trial analyses and all trials were at moderate risk of bias and two were published in abstract form only. Authors’ conclusions Ideally, large, multi-centre supporting trials are needed as outcomes were incompletely reported in included trials in this review. It may be beneficial to design a multi-arm trial comparing 3, 24 and 96 hour infusions or maybe looking at different schedules. In the absence of such trials, the decision to offer short or long infusions in advanced adenocarcinoma may need to be individualised, although it certainly appears that women have less toxicity, apart from sensory nerve damage, with a shorter infusion. Efficacy appearing similar regardless of infusion duration. PMID:21563139

Heated, humidified air for the common cold.

PubMed

Singh, Meenu; Singh, Manvi

2011-05-11

Heated, humidified air has long been used by sufferers of the common cold. The theoretical basis is that steam may help congested mucus drain better and heat may destroy the cold virus as it does in vitro. To assess the effects of inhaling heated water vapour (steam) in the treatment of the common cold by comparing symptoms, viral shedding and nasal resistance. In this updated review we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to July Week 1, 2010), EMBASE (1990 to July 2010) and Current Contents (1994 to July 2010). Randomised controlled trials (RCTs) using heated water vapour in participants with the common cold or participants with experimentally-induced common cold. We reviewed all retrieved articles and excluded any articles, editorials and abstracts with inadequate outcome descriptions. The studies we included were subjected to a methodological assessment. Six trials (394 trial participants) were included. Three trials in which patient data could be pooled found benefits of steam for symptom relief for the common cold (odds ratio (OR) 0.31; 95% confidence interval (CI) 0.16 to 0.60). However, results on symptom indices were equivocal. No studies demonstrated an exacerbation of clinical symptom scores. One study conducted in the USA demonstrated worsened nasal resistance, while an earlier Israeli study showed improvement. One study examined viral shedding and antibody titres in nasal washings; there was no change in either between treatment and placebo groups. Minor side effects (including discomfort or irritation of the nose) were reported in some studies. Steam inhalation has not shown any consistent benefits in the treatment of the common cold, hence is not recommended in the routine treatment of common cold symptoms until more double-blind, randomized trials with a standardised treatment modality are conducted.

Continuous passive motion and physical therapy (CPM) versus physical therapy (PT) versus delayed physical therapy (DPT) after surgical release for elbow contractures; a study protocol for a prospective randomized controlled trial.

PubMed

Viveen, Jetske; Doornberg, Job N; Kodde, Izaak F; Goossens, Pjotr; Koenraadt, Koen L M; The, Bertram; Eygendaal, Denise

2017-11-22

The elbow is prone to stiffness after trauma. To regain functional elbow motion several conservative- and surgical treatment options are available. Conservative treatment includes physical therapy, intra-articular injections with corticosteroids and a static progressive or dynamic splinting program. If conservative treatment fails, an operative release of the posttraumatic stiff elbow is often performed. The best Evidence-Based rehabilitation protocol for patients after an operative release is unknown to date and differs per surgeon, hospital and country. Options include early- or delayed motion supervised by a physical therapist, immediate continuous passive motion (CPM), (night) splinting and a static progressive or dynamic splinting program. The SET-Study (Stiff Elbow Trial) is a single-centre, prospective, randomized controlled trial. The primary objective of this study is to compare the active Range of Motion (ROM) (flexion arc and rotational arc) twelve months after surgery between three groups. The first group will receive in-hospital CPM in combination with early motion Physical Therapy (PT) supervised by a physical therapist, the second group will receive only in-hospital early motion PT supervised by a physical therapist and the third group will receive outpatient supervised PT from postoperative day seven till ten. Secondary outcome measures will be Patient Reported Outcome Measures (PROMs) including the Mayo Elbow Performance Score (MEPS), the Oxford Elbow Score (OES), the quick Disabilities of Arm, Shoulder and Hand (qDASH) score, Visual Analogue pain Scale in rest and activity (VAS), Pain Catastrophizing Scale (PCS), the Short Form (SF)-36, the Centre for Epidemiological Studies Depression Scale Revised (CESD-R) and the Work Rehabilitation Questionnaire (WORQ) for the upper limb. A successful completion of this trial will provide evidence on the best rehabilitation protocol in order to (re)gain optimal motion after surgical release of the stiff elbow. The trial is registered at the Dutch Trial Register: NTR6067 , 31-8-2016.

Efficacy of cocaine contingency management in heroin-assisted treatment: Results of a randomized controlled trial.

PubMed

Blanken, Peter; Hendriks, Vincent M; Huijsman, Ineke A; van Ree, Jan M; van den Brink, Wim

2016-07-01

To determine the efficacy of contingency management (CM), targeting cocaine use, as an add-on intervention for heroin dependent patients in supervised heroin-assisted treatment (HAT) with frequent cocaine use. Multi-center, open-label, parallel group, randomized controlled trial. Twelve specialized addiction treatment centers for HAT in The Netherlands; April 2006-January 2011. 214 chronic, treatment-refractory heroin dependent patients in HAT, with frequent cocaine use. Routine, daily supervised diacetylmorphine treatment, co-prescribed with oral methadone (HAT), with and without 6 months contingency management for cocaine use as an add-on intervention; HAT+CM and HAT-only, respectively. Primary outcome was the longest, uninterrupted duration of cocaine abstinence, based upon laboratory urinalysis. Secondary outcome measures included other cocaine-related measures, treatment retention in HAT, and multi-domain health-related treatment response. In an intention-to-treat analysis, HAT+CM was more effective than HAT-only in promoting longer, uninterrupted duration of cocaine abstinence (3.7 weeks versus 1.6 weeks; negative binomial regression: Exp(B)=2.34, 95%-CI: 1.70-3.23; p<0.001). This result remained significant in sensitivity analyses and was supported by all secondary, cocaine-related outcome measures. Treatment retention in HAT was high (91.6%) with no difference between the groups. The improvement in multi-domain health-related treatment response during the trial was numerically higher in HAT+CM (from 37.4% to 53.1%; +15.7%) than in HAT-only (from 44.5% to 46.5%; +2.0%), but this difference was statistically not significant. Contingency management is an effective add-on intervention to promote longer, uninterrupted periods of cocaine abstinence in chronic, treatment-refractory heroin dependent patients in heroin-assisted treatment with frequent cocaine use. The trial has been registered in The Netherlands National Trial Register under clinical trial registration number NTR4728. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

GAME (Goals - Activity - Motor Enrichment): protocol of a single blind randomised controlled trial of motor training, parent education and environmental enrichment for infants at high risk of cerebral palsy.

PubMed

Morgan, Catherine; Novak, Iona; Dale, Russell C; Guzzetta, Andrea; Badawi, Nadia

2014-10-07

Cerebral palsy is the most common physical disability of childhood and early detection is possible using evidence based assessments. Systematic reviews indicate early intervention trials rarely demonstrate efficacy for improving motor outcomes but environmental enrichment interventions appear promising. This study is built on a previous pilot study and has been designed to assess the effectiveness of a goal - oriented motor training and enrichment intervention programme, "GAME", on the motor outcomes of infants at very high risk of cerebral palsy (CP) compared with standard community based care. A two group, single blind randomised controlled trial (n = 30) will be conducted. Eligible infants are those diagnosed with CP or designated "at high risk of CP" on the basis of the General Movements Assessment and/or abnormal neuroimaging. A physiotherapist and occupational therapist will deliver home-based GAME intervention at least fortnightly until the infant's first birthday. The intervention aims to optimize motor function and engage parents in developmental activities aimed at enriching the home learning environment. Primary endpoint measures will be taken 16 weeks after intervention commences with the secondary endpoint at 12 months and 24 months corrected age. The primary outcome measure will be the Peabody Developmental Motor Scale second edition. Secondary outcomes measures include the Gross Motor Function Measure, Bayley Scales of Infant and Toddler Development, Affordances in the Home Environment for Motor Development - Infant Scale, and the Canadian Occupational Performance Measure. Parent well-being will be monitored using the Depression Anxiety and Stress Scale. This paper presents the background, design and intervention protocol of a randomised trial of a goal driven, motor learning approach with customised environmental interventions and parental education for young infants at high risk of cerebral palsy. This trial is registered on the Australian New Zealand Clinical Trial register: ACTRN12611000572965.

Perioperative antibiotic prophylaxis in the treatment of acute cholecystitis (PEANUTS II trial): study protocol for a randomized controlled trial.

PubMed

Loozen, Charlotte S; van Santvoort, Hjalmar C; van Geloven, Antoinette A W; Nieuwenhuijzen, Grard A P; de Reuver, Philip R; Besselink, Mark H G; Vlaminckx, Bart; Kelder, Johannes C; Knibbe, Catherijne A J; Boerma, Djamila

2017-08-23

The additional value of perioperative antibiotic prophylaxis in preventing infectious complications after emergency cholecystectomy for acute cholecystitis is a much-debated subject in the surgical community. Evidence-based guidelines are lacking, and consequently the use of antibiotic prophylaxis varies greatly among surgeons and hospitals. Recently, high-level evidence became available demonstrating that postoperative antibiotic prophylaxis in patients with acute cholecystitis does not reduce the risk of infectious complications. Preoperative antibiotic prophylaxis in relation to the risk of infectious complications, however, has never been studied. The PEANUTS II trial is a randomized, controlled, multicenter, open-label noninferiority trial whose aim is to determine the utility of preoperative antibiotic prophylaxis in patients undergoing emergency cholecystectomy for acute calculous cholecystitis. Patients with mild or moderate acute cholecystitis, as defined according the Tokyo Guidelines, will be randomly assigned to a single preoperative dose of antibiotic prophylaxis (2000 mg of first-generation cephalosporin delivered intravenously) or no antibiotic prophylaxis before emergency cholecystectomy. The primary endpoint is a composite endpoint consisting of all postoperative infectious complications occurring during the first 30 days after surgery. Secondary endpoints include all the individual components of the primary endpoint, all other complications, duration of hospital stay, and total costs. The hypothesis is that the absence of antibiotic prophylaxis is noninferior to the presence of antibiotic prophylaxis. A noninferiority margin of 10% is assumed. With a 1-sided risk of 2.5% and a power of 80%, a total of 454 subjects will have to be included. Analysis will be performed according to the intention-to-treat principle. The PEANUTS II trial will provide evidence-based advice concerning the utility of antibiotic prophylaxis in patients undergoing emergency cholecystectomy for acute calculous cholecystitis. Netherlands Trial Register, NTR5802 . Registered on 4 June 2016.

24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial.

PubMed

Soininen, Hilkka; Solomon, Alina; Visser, Pieter Jelle; Hendrix, Suzanne B; Blennow, Kaj; Kivipelto, Miia; Hartmann, Tobias

2017-12-01

Nutrition is an important modifiable risk factor in Alzheimer's disease. Previous trials of the multinutrient Fortasyn Connect showed benefits in mild Alzheimer's disease dementia. LipiDiDiet investigated the effects of Fortasyn Connect on cognition and related measures in prodromal Alzheimer's disease. Here, we report the 24-month results of the trial. LipiDiDiet was a 24-month randomised, controlled, double-blind, parallel-group, multicentre trial (11 sites in Finland, Germany, the Netherlands, and Sweden), with optional 12-month double-blind extensions. The trial enrolled individuals with prodromal Alzheimer's disease, defined according to the International Working Group (IWG)-1 criteria. Participants were randomly assigned (1:1) to active product (125 mL once-a-day drink containing Fortasyn Connect) or control product. Randomisation was computer-generated centrally in blocks of four, stratified by site. All study personnel and participants were masked to treatment assignment. The primary endpoint was change in a neuropsychological test battery (NTB) score. Analysis was by modified intention to treat. Safety analyses included all participants who consumed at least one study product dose. This trial is registered with the Dutch Trial Register, number NTR1705. Between April 20, 2009, and July 3, 2013, 311 of 382 participants screened were randomly assigned to the active group (n=153) or control group (n=158). Mean change in NTB primary endpoint was -0·028 (SD 0·453) in the active group and -0·108 (0·528) in the control group; estimated mean treatment difference was 0·098 (95% CI -0·041 to 0·237; p=0·166). The decline in the control group was less than the prestudy estimate of -0·4 during 24 months. 66 (21%) participants dropped out of the study. Serious adverse events occurred in 34 (22%) participants in the active group and 30 (19%) in control group (p=0·487), none of which were regarded as related to the study intervention. The intervention had no significant effect on the NTB primary endpoint over 2 years in prodromal Alzheimer's disease. However, cognitive decline in this population was much lower than expected, rendering the primary endpoint inadequately powered. Group differences on secondary endpoints of disease progression measuring cognition and function and hippocampal atrophy were observed. Further study of nutritional approaches with larger sample sizes, longer duration, or a primary endpoint more sensitive in this pre-dementia population, is needed. European Commission 7th Framework Programme. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

A Feasibility Randomised Controlled Trial of the New Orleans Intervention for Infant Mental Health: A Study Protocol

PubMed Central

Fitzpatrick, Bridie; Watson, Nicholas; Cotmore, Richard; Wilson, Philip; Donaldson, Julia; Boyd, Kathleen; Zeanah, Charles; Norrie, John; Messow, Martina; Turner, Fiona; Irving, Susan

2013-01-01

Child maltreatment is associated with life-long social, physical, and mental health problems. Intervening early to provide maltreated children with safe, nurturing care can improve outcomes. The need for prompt decisions about permanent placement (i.e., regarding adoption or return home) is internationally recognised. However, a recent Glasgow audit showed that many maltreated children “revolve” between birth families and foster carers. This paper describes the protocol of the first exploratory randomised controlled trial of a mental health intervention aimed at improving placement permanency decisions for maltreated children. This trial compares an infant's mental health intervention with the new enhanced service as usual for maltreated children entering care in Glasgow. As both are new services, the trial is being conducted from a position of equipoise. The outcome assessment covers various fields of a child's neurodevelopment to identify problems in any ESSENCE domain. The feasibility, reliability, and developmental appropriateness of all outcome measures are examined. Additionally, the potential for linkage with routinely collected data on health and social care and, in the future, education is explored. The results will inform a definitive randomised controlled trial that could potentially lead to long lasting benefits for the Scottish population and which may be applicable to other areas of the world. This trial is registered with ClinicalTrials.gov (NC01485510). PMID:24023537

Topical treatments for fungal infections of the skin and nails of the foot.

PubMed

Crawford, F; Hollis, S

2007-07-18

Fungal infections of the feet normally occur in the outermost layer of the skin (epidermis). The skin between the toes is a frequent site of infection which can cause pain and itchiness. Fungal infections of the nail (onychomycosis) can affect the entire nail plate. To assess the effects of topical treatments in successfully treating (rate of treatment failure) fungal infections of the skin of the feet and toenails and in preventing recurrence. We searched the Cochrane Skin Group Specialised Register (January 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE and EMBASE (from inception to January 2005). We screened the Science Citation Index, BIOSIS, CAB - Health and Healthstar, CINAHL DARE, NHS Economic Evaluation Database and EconLit (March 2005). Bibliographies were searched. Randomised controlled trials (RCTs) using participants who had mycologically diagnosed fungal infections of the skin and nails of the foot. Two authors independently summarised the included trials and appraised their quality of reporting using a structured data extraction tool. Of the 144 identified papers, 67 trials met the inclusion criteria. Placebo-controlled trials yielded the following pooled risk ratios (RR) of treatment failure for skin infections: allylamines RR 0.33 (95% CI 0.24 to 0.44); azoles RR 0.30 (95% CI 0.20 to 0.45); ciclopiroxolamine RR 0.27 (95% CI 0.11 to 0.66); tolnaftate RR 0.19 (95% CI 0.08 to 0.44); butenafine RR 0.33 (95% CI 0.24 to 0.45); undecanoates RR 0.29 (95% CI 0.12 - 0.70). Meta-analysis of 11 trials comparing allylamines and azoles showed a risk ratio of treatment failure RR 0.63 (95% CI 0.42 to 0.94) in favour of allylamines. Evidence for the management of topical treatments for infections of the toenails is sparser. There is some evidence that ciclopiroxolamine and butenafine are both effective but they both need to be applied daily for prolonged periods (at least 1 year). The 6 trials of nail infections provided evidence that topical ciclopiroxolamine has poor cure rates and that amorolfine might be substantially more effective but more research is required. Placebo-controlled trials of allylamines and azoles for athlete's foot consistently produce much higher percentages of cure than placebo. Allylamines cure slightly more infections than azoles and are now available OTC. Further research into the effectiveness of antifungal agents for nail infections is required.

Intermittent preventive antimalarial treatment for children with anaemia.

PubMed

Athuman, Mwaka; Kabanywanyi, Abdunoor M; Rohwer, Anke C

2015-01-13

Anaemia is a global public health problem. Children under five years of age living in developing countries (mostly Africa and South-East Asia) are highly affected. Although the causes for anaemia are multifactorial, malaria has been linked to anaemia in children living in malaria-endemic areas. Administering intermittent preventive antimalarial treatment (IPT) to children might reduce anaemia, since it could protect children from new Plasmodium parasite infection (the parasites that cause malaria) and allow their haemoglobin levels to recover. To assess the effect of IPT for children with anaemia living in malaria-endemic areas. We searched the Cochrane Infectious Diseases Group Specialized Register, Cochrane Central of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; and LILACS. We also searched the World Health Organization (WHO) International Clinical Trial Registry Platform and metaRegister of Controlled Trials (mRCT) for ongoing trials up to 4 December 2014. Randomized controlled trials (RCTs) evaluating the effect of IPT on children with anaemia. Two review authors independently extracted data and assessed risk of bias. We analysed data by conducting meta-analyses, stratifying data according to whether participants received iron supplements or not. We used GRADE to assess the quality of evidence. Six trials with 3847 participants met our inclusion criteria. Trials were conducted in areas of low malaria endemicity (three trials), and moderate to high endemicity (three trials). Four trials were in areas of seasonal malaria transmission. Iron was given to all children in two trials, and evaluated in a factorial design in a further two trials.IPT for children with anaemia probably has little or no effect on the proportion anaemic at 12 weeks follow-up (four trials, 2237 participants, (moderate quality evidence).IPT in anaemic children probably increases the mean change in haemoglobin levels from baseline to follow-up at 12 weeks on average by 0.32 g/dL (MD 0.32, 95% CI 0.19 to 0.45; four trials, 1672 participants, moderate quality evidence); and may improve haemoglobin levels at 12 weeks (MD 0.35, 95% CI 0.06 to 0.64; four trials, 1672 participants, low quality evidence). For both of these outcomes, subgroup analysis did not demonstrate a difference between children receiving iron and those that did not.IPT for children with anaemia probably has little or no effect on mortality or hospital admissions at six months (three trials, 3160 participants moderate quality evidence). Subgroup analysis did not show a difference between those children receiving iron supplements and those that did not. Trials did show a small effect on average haemoglobin levels but this did not appear to translate into an effect on mortality and hospital admissions. Three of the six trials were conducted in low endemicity areas where transmission is low and thus any protective effect is likely to be modest.

Antibiotics for preventing suppurative complications from undifferentiated acute respiratory infections in children under five years of age.

PubMed

Alves Galvão, Márcia G; Rocha Crispino Santos, Marilene Augusta; Alves da Cunha, Antonio J L

2016-02-29

Undifferentiated acute respiratory infections (ARIs) are a large and heterogeneous group of infections not clearly restricted to one specific part of the upper respiratory tract, which last for up to seven days. They are more common in pre-school children in low-income countries and are responsible for 75% of the total amount of prescribed antibiotics in high-income countries. One possible rationale for prescribing antibiotics is the wish to prevent bacterial complications. To assess the effectiveness and safety of antibiotics in preventing bacterial complications in children aged two months to 59 months with undifferentiated ARIs. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to August week 1, 2015) and EMBASE (1974 to August 2015). Randomised controlled trials (RCTs) or quasi-RCTs comparing antibiotic prescriptions with placebo or no treatment in children aged two months to 59 months with an undifferentiated ARI for up to seven days. Two review authors independently assessed trial quality and extracted and analysed data using the standard Cochrane methodological procedures. We identified four trials involving 1314 children. Three trials investigated the use of amoxicillin/clavulanic acid to prevent otitis and one investigated ampicillin to prevent pneumonia.The use of amoxicillin/clavulanic acid compared to placebo to prevent otitis showed a risk ratio (RR) of 0.70 (95% confidence interval (CI) 0.45 to 1.11, three trials, 414 selected children, moderate-quality evidence). Methods of random sequence generation and allocation concealment were not clearly stated in two trials. Performance, detection and reporting bias could not be ruled out in three trials.Ampicillin compared to supportive care (continuation of breastfeeding, clearing of the nose and paracetamol for fever control) to prevent pneumonia showed a RR of 1.05 (95% CI 0.74 to 1.49, one trial, 889 selected children, moderate-quality evidence). The trial was non-blinded. Random sequence generation and allocation concealment methods were not clearly stated, so the possibility of reporting bias could not be ruled out.Harm outcomes could not be analysed as they were expressed only in percentages.We found no studies assessing mastoiditis, quinsy, abscess, meningitis, hospital admission or death. There is insufficient evidence for antibiotic use as a means of reducing the risk of otitis or pneumonia in children up to five years of age with undifferentiated ARIs. Further high-quality research is needed to provide more definitive evidence of the effectiveness of antibiotics in this population.

Carnitine for fatigue in multiple sclerosis.

PubMed

Tejani, Aaron M; Wasdell, Michael; Spiwak, Rae; Rowell, Greg; Nathwani, Shabita

2012-05-16

Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients. To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose. A literature search was performed using Cochrane MS Group Trials Register (09 September 2011), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2011, issue 3", MEDLINE (PubMed) (1966-09 September 2011), EMBASE (1974-09 September 2011), and www.clinicaltrials.gov for ongoing trials retrieval. Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied. Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults affected by multiple sclerosis with a clinical diagnosis of fatigue associated with multiple sclerosis were included. Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer, however this was not necessary.The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up. The search identified one ongoing randomized, placebo-controlled, cross-over trial (expected completion 2013) and one completed randomized, active-comparator, cross-over trial. In the completed study, adult patients with relapsing-remitting and secondary progressive MS were exposed to both acetyl L-carnitine 2 grams daily and amantadine 200 mg daily The effects of carnitine on fatigue are unclear. There was no difference between carnitine and amantadine for the number of patients withdrawing from the study due to an adverse event (relative risk ratio 0.20; 95% confidence interval 0.03 to 1.55) and no patients experienced a serious adverse event in either treatment group. Mortality and quality of life were not reported. There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators. Results of the ongoing trial are eagerly anticipated in order to provide clarity.

The NAPRESSIM trial: the use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine in elective hepatobiliary surgery: a study protocol and statistical analysis plan for a randomised controlled trial.

PubMed

Cosgrave, David; Galligan, Marie; Soukhin, Era; McMullan, Victoria; McGuinness, Siobhan; Puttappa, Anand; Conlon, Niamh; Boylan, John; Hussain, Rabia; Doran, Peter; Nichol, Alistair

2017-12-29

Intrathecally administered morphine is effective as part of a postoperative analgesia regimen following major hepatopancreaticobiliary surgery. However, the potential for postoperative respiratory depression at the doses required for effective analgesia currently limits its clinical use. The use of a low-dose, prophylactic naloxone infusion following intrathecally administered morphine may significantly reduce postoperative respiratory depression. The NAPRESSIM trial aims to answer this question. 'The use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine' trial is an investigator-led, single-centre, randomised, double-blind, placebo-controlled, double-arm comparator study. The trial will recruit 96 patients aged > 18 years, undergoing major open hepatopancreaticobiliary resections, who are receiving intrathecally administered morphine as part of a standard anaesthetic regimen. It aims to investigate whether the prophylactic administration of naloxone via intravenous infusion compared to placebo will reduce the proportion of episodes of respiratory depression in this cohort of patients. Trial patients will receive an infusion of naloxone or placebo, commenced within 1 h of postoperative extubation continued until the first postoperative morning. The primary outcome is the rate of respiratory depression in the intervention group as compared to the placebo group. Secondary outcomes include pain scores, rates of nausea and vomiting, pruritus, sedation scores and adverse outcomes. We will also employ a novel, non-invasive, respiratory minute volume monitor (ExSpiron 1Xi, Respiratory Motion, Inc., 411 Waverley Oaks Road, Building 1, Suite 150, Waltham, MA, USA) to assess the monitor's accuracy for detecting respiratory depression. The trial aims to provide a clear management plan to prevent respiratory depression after the intrathecal administration of morphine, and thereby improve patient safety. ClinicalTrials.gov, ID: NCT02885948 . Registered retrospectively on 4 July 2016. Protocol Version 2.0, 3 April 2017. Protocol identification (code or reference number): UCDCRC/15/006 EudraCT registration number: 2015-003504-22. Registered on 5 August 2015.

The synchronized trial on expectant mothers with depressive symptoms by omega-3 PUFAs (SYNCHRO): Study protocol for a randomized controlled trial.

PubMed

Nishi, Daisuke; Su, Kuan-Pin; Usuda, Kentaro; Chiang, Yi-Ju Jill; Guu, Tai-Wei; Hamazaki, Kei; Nakaya, Naoki; Sone, Toshimasa; Sano, Yo; Tachibana, Yoshiyuki; Ito, Hiroe; Isaka, Keiich; Hashimoto, Kenji; Hamazaki, Tomohito; Matsuoka, Yutaka J

2016-09-15

Maternal depression can be harmful to both mothers and their children. Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been investigated as an alternative intervention for pregnant women with depressive symptoms because of the supporting evidence from clinical trials in major depression, the safety advantage, and its anti-inflammatory and neuroplasticity effects. This study examines the efficacy of omega-3 PUFA supplementation for pregnant women with depressive symptoms in Taiwan and Japan, to provide evidence available for Asia. The rationale and protocol of this trial are reported here. The Synchronized Trial on Expectant Mothers with Depressive Symptoms by Omega-3 PUFAs (SYNCHRO) is a multicenter, double-blind, parallel group, randomized controlled trial. Participants will be randomized to either the omega-3 PUFAs arm (1,200 mg eicosapentaenoic acid and 600 mg docosahexaenoic acid daily) or placebo arm. Primary outcome is total score on the Hamilton Rating Scale for Depression (HAMD) at 12 weeks after the start of the intervention. We will randomize 56 participants to have 90 % power to detect a 4.7-point difference in mean HAMD scores with omega-3 PUFAs compared with placebo. Because seafood consumption varies across countries and this may have a major effect on the efficacy of omega-3 PUFA supplementation, 56 participants will be recruited at each site in Taiwan and Japan, for a total number of 112 participants. Secondary outcomes include depressive symptoms at 1 month after childbirth, diagnosis of major depressive disorder, changes in omega-3 PUFAs concentrations and levels of biomarkers at baseline and at 12 weeks' follow-up, and standard obstetric outcomes. Data analyses will be by intention to treat. The trial was started in June 2014 and is scheduled to end in February 2018. The trial is expected to provide evidence that can contribute to promoting mental health among mothers and children in Asian populations. Clinicaltrials.gov: NCT02166424 . Registered 15 June 2014; University Hospital Medical Information Network (UMIN) Center: UMIN000017979. Registered 20 May 2015.

Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases.

PubMed

Rambaldi, A; Jacobs, B P; Iaquinto, G; Gluud, C

2005-04-18

Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases. To assess the beneficial and harmful effects of milk thistle or milk thistle constituents versus placebo or no intervention in patients with alcoholic liver disease and/or viral liver diseases (hepatitis B and hepatitis C). The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and full text searches were combined (December 2003). Manufacturers and researchers in the field were contacted. Only randomised clinical trials in patients with alcoholic and/or hepatitis B or C virus liver diseases (acute and chronic) were included. Interventions encompassed milk thistle at any dose or duration versus placebo or no intervention. The trials could be double blind, single blind, or unblinded. The trials could be unpublished or published and no language limitations were applied. The primary outcome measure was mortality. Binary outcomes are reported as relative risks (RR) with 95% confidence interval (CI). Subgroup analyses were performed with regard to methodological quality. Thirteen randomised clinical trials assessed milk thistle in 915 patients with alcoholic and/or hepatitis B or C virus liver diseases. The methodological quality was low: only 23% of the trials reported adequate allocation concealment and only 46% were considered adequately double-blinded. Milk thistle versus placebo or no intervention had no significant effect on mortality (RR 0.78, 95% CI 0.53 to 1.15), complications of liver disease (RR 0.95, 95% CI 0.83 to 1.09), or liver histology. Liver-related mortality was significantly reduced by milk thistle in all trials (RR 0.50, 95% CI 0.29 to 0.88), but not in high-quality trials (RR 0.57, 95% CI 0.28 to 1.19). Milk thistle was not associated with a significantly increased risk of adverse events (RR 0.83, 95% CI 0.46 to 1.50). Our results question the beneficial effects of milk thistle for patients with alcoholic and/or hepatitis B or C virus liver diseases and highlight the lack of high-quality evidence to support this intervention. Adequately conducted and reported randomised clinical trials on milk thistle versus placebo are needed.

Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases.

PubMed

Rambaldi, A; Jacobs, B P; Gluud, C

2007-10-17

Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases. To assess the beneficial and harmful effects of milk thistle or milk thistle constituents versus placebo or no intervention in patients with alcoholic liver disease and/or viral liver diseases (hepatitis B and hepatitis C). The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and full text searches were combined (July 2007). Manufacturers and researchers in the field were contacted. Only randomised clinical trials in patients with alcoholic and/or hepatitis B or C virus liver diseases (acute and chronic) were included. Interventions encompassed milk thistle at any dose or duration versus placebo or no intervention. The trials could be double blind, single blind, or unblinded. The trials could be unpublished or published and no language limitations were applied. The primary outcome measure was mortality. Binary outcomes are reported as relative risks (RR) with 95% confidence interval (CI). Subgroup analyses were performed with regard to methodological quality. Eighteen randomised clinical trials assessed milk thistle in 1088 patients with alcoholic and/or hepatitis B or C virus liver diseases. The methodological quality was low: only 28.6% of the trials reported high methodological quality characteristics. Milk thistle versus placebo or no intervention had no significant effect on mortality (RR 0.78, 95% CI 0.53 to 1.15), complications of liver disease (RR 0.95, 95% CI 0.83 to 1.09), or liver histology. Liver-related mortality was significantly reduced by milk thistle in all trials (RR 0.50, 95% CI 0.29 to 0.88), but not in high-quality trials (RR 0.57, 95% CI 0.28 to 1.19). Milk thistle was not associated with a significantly increased risk of adverse events (RR 0.83, 95% CI 0.46 to 1.50). Our results question the beneficial effects of milk thistle for patients with alcoholic and/or hepatitis B or C virus liver diseases and highlight the lack of high-quality evidence to support this intervention. Adequately conducted and reported randomised clinical trials on milk thistle versus placebo are needed.

Insufficient evidence for the role of school dental screening in improving oral health.

PubMed

Holmes, Richard D

2018-03-23

Data sourcesThe Cochrane Oral Health's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, the US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform databases.Study selectionRandomised controlled trials (cluster or parallel) evaluating school dental screening compared with no intervention or with one type of screening compared with another were included.Data extraction and synthesisTwo reviewers independently abstracted data and assessed risk of bias. Risk ratios were calculated for dichotomous outcomes, with data being pooled where appropriate. The GRADE approach was used to interpret findings.ResultsSix trials involving 19,498 children were included. Two were considered to be at low risk of bias, three at unclear risk and one at high risk. No conclusions could be made from four studies comparing traditional screening versus no screening because the evidence was inconsistent. Two trials evaluating criteria-based screening versus no screening suggested a possible benefit; RR = 1.07 (95% CI; 0.99-1.16). No difference was found when comparing criteria-based screening with traditional screening, RR = 1.01, (95% CI; 0.94-1.08). No trials reported on long-term follow-up or cost-effectiveness and adverse events.ConclusionsThe trials included in this review evaluated short-term effects of screening, assessing follow-up periods of three to eight months. We found very low certainty evidence that was insufficient to allow us to draw conclusions about whether there is a role for traditional school dental screening in improving dental attendance. For criteria-based screening, we found low-certainty evidence that it may improve dental attendance when compared to no screening. However, when compared to traditional screening there was no evidence of a difference in dental attendance (very low-certainty evidence).We found low-certainty evidence to conclude that personalised or specific referral letters improve dental attendance when compared to non-specific counterparts. We also found low-certainty evidence that screening supplemented with motivation (oral health education and offer of free treatment) improves dental attendance in comparison to screening alone.We did not find any trials addressing cost-effectiveness and adverse effects of school dental screening.

Intensive home treatment for patients in acute psychiatric crisis situations: a multicentre randomized controlled trial.

PubMed

Cornelis, Jurgen; Barakat, Ansam; Dekker, Jack; Schut, Tessy; Berk, Sandra; Nusselder, Hans; Ruhl, Nikander; Zoeteman, Jeroen; Van, Rien; Beekman, Aartjan; Blankers, Matthijs

2018-02-27

Hospitalization is a common method to intensify care for patients experiencing a psychiatric crisis. A short-term, specialised, out-patient crisis intervention by a Crisis Resolution Team (CRT) in the Netherlands, called Intensive Home Treatment (IHT), is a viable intervention which may help reduce hospital admission days. However, research on the (cost-)effectiveness of alternatives to hospitalisation such as IHT are scarce. In the study presented in this protocol, IHT will be compared to care-as-usual (CAU) in a randomized controlled trial (RCT). CAU comprises low-intensity outpatient care and hospitalisation if necessary. In this RCT it is hypothesized that IHT will reduce inpatient days by 33% compared to CAU while safety and clinical outcomes will be non-inferior. Secondary hypotheses are that treatment satisfaction of patients and their relatives are expected to be higher in the IHT condition compared to CAU. A 2-centre, 2-arm Zelen double consent RCT will be employed. Participants will be recruited in the Amsterdam area, the Netherlands. Clinical assessments will be carried out at baseline and at 6, 26 and 52 weeks post treatment allocation. The primary outcome measure is the number of admission days. Secondary outcomes include psychological well-being, safety and patients' and their relatives' treatment satisfaction. Alongside this RCT an economic evaluation will be carried out to assess the cost-effectiveness and cost-utility of IHT compared to CAU. RCTs on the effectiveness of crisis treatment in psychiatry are scarce and including patients in studies performed in acute psychiatric crisis care is a challenge due to the ethical and practical hurdles. The Zelen design may offer a feasible opportunity to carry out such an RCT. If our study finds that IHT is a safe and cost-effective alternative for CAU it may help support a further decrease of in-patient bed days and may foster the widespread implementation of IHT by mental health care organisations internationally. The trial is registered in the Netherlands Trial Register as # NTR-6151 . Registered 23 November 2016.

Electromechanical and robot-assisted arm training for improving activities of daily living, arm function, and arm muscle strength after stroke.

PubMed

Mehrholz, Jan; Pohl, Marcus; Platz, Thomas; Kugler, Joachim; Elsner, Bernhard

2015-11-07

Electromechanical and robot-assisted arm training devices are used in rehabilitation, and may help to improve arm function after stroke. To assess the effectiveness of electromechanical and robot-assisted arm training for improving activities of daily living, arm function, and arm muscle strength in people after stroke. We also assessed the acceptability and safety of the therapy. We searched the Cochrane Stroke Group's Trials Register (last searched February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2015, Issue 3), MEDLINE (1950 to March 2015), EMBASE (1980 to March 2015), CINAHL (1982 to March 2015), AMED (1985 to March 2015), SPORTDiscus (1949 to March 2015), PEDro (searched April 2015), Compendex (1972 to March 2015), and Inspec (1969 to March 2015). We also handsearched relevant conference proceedings, searched trials and research registers, checked reference lists, and contacted trialists, experts, and researchers in our field, as well as manufacturers of commercial devices. Randomised controlled trials comparing electromechanical and robot-assisted arm training for recovery of arm function with other rehabilitation or placebo interventions, or no treatment, for people after stroke. Two review authors independently selected trials for inclusion, assessed trial quality and risk of bias, and extracted data. We contacted trialists for additional information. We analysed the results as standardised mean differences (SMDs) for continuous variables and risk differences (RDs) for dichotomous variables. We included 34 trials (involving 1160 participants) in this update of our review. Electromechanical and robot-assisted arm training improved activities of daily living scores (SMD 0.37, 95% confidence interval (CI) 0.11 to 0.64, P = 0.005, I² = 62%), arm function (SMD 0.35, 95% CI 0.18 to 0.51, P < 0.0001, I² = 36%), and arm muscle strength (SMD 0.36, 95% CI 0.01 to 0.70, P = 0.04, I² = 72%), but the quality of the evidence was low to very low. Electromechanical and robot-assisted arm training did not increase the risk of participant drop-out (RD 0.00, 95% CI -0.02 to 0.03, P = 0.84, I² = 0%) with moderate-quality evidence, and adverse events were rare. People who receive electromechanical and robot-assisted arm and hand training after stroke might improve their activities of daily living, arm and hand function, and arm and hand muscle strength. However, the results must be interpreted with caution because the quality of the evidence was low to very low, and there were variations between the trials in the intensity, duration, and amount of training; type of treatment; and participant characteristics.

Area-wide traffic calming for preventing traffic related injuries.

PubMed

Bunn, F; Collier, T; Frost, C; Ker, K; Roberts, I; Wentz, R

2003-01-01

It is estimated that by 2020 road traffic crashes will have moved from ninth to third in the world disease burden ranking, as measured in disability adjusted life years, and second in developing countries. The identification of effective strategies for the prevention of traffic related injuries is of global health importance. Area-wide traffic calming schemes that discourage through traffic on residential roads is one such strategy. To evaluate the effectiveness of area-wide traffic calming in preventing traffic related crashes, injuries, and deaths. We searched the following electronic databases: Cochrane Injuries Group's Specialised Register, Cochrane Controlled Trials Register, MEDLINE, EMBASE and TRANSPORT (NTIS, TRIS, TRANSDOC). We searched the web sites of road safety organisations, handsearched conference proceedings, checked reference lists of relevant papers and contacted experts in the area. The search was not restricted by language or publication status. Randomised controlled trials, and controlled before-after studies of area-wide traffic calming schemes. Two reviewers independently extracted data on type of study, characteristics of intervention and control areas, and length of data collection periods. Before and after data were collected on the total number of road traffic crashes, all road user deaths and injuries, pedestrian-motor vehicle collisions and road user deaths. The statistical package STATA was used to calculate rate ratios for each study, which were then pooled to give an overall estimate using a random effects model. We found no randomised controlled trials, but 16 controlled before-after trials met our inclusion criteria. Seven studies were done in Germany, six in the UK, two in Australia and one in the Netherlands. There were no studies in low or middle income countries. Eight trials reported the number of road traffic crashes resulting in deaths. The pooled rate ratio was 0.63 (0.14, 2.59 95% CI). Sixteen studies reported the number of road traffic crashes resulting in injuries (fatal and non fatal). The pooled rate ratio was 0.89 (0.80, 1.00 95% CI). Nine studies reported the total number of road traffic crashes. The pooled rate ratio was 0.95 (0.81, 1.11 95% CI). Thirteen trials reported the number of pedestrian-motor vehicle collisions. The pooled rate ratio was 1.00 (0.84, 1.18). There was significant heterogeneity for the total number of crashes and deaths and injuries. The results from this review suggest that area-wide traffic calming in towns and cities may be a promising intervention for reducing the number of road traffic injuries, and deaths. However, further rigorous evaluations of this intervention are needed.

WHEDA study: Effectiveness of occupational therapy at home for older people with dementia and their caregivers - the design of a pragmatic randomised controlled trial evaluating a Dutch programme in seven German centres

PubMed Central

Voigt-Radloff, Sebastian; Graff, Maud; Leonhart, Rainer; Schornstein, Katrin; Vernooij-Dassen, Myrra; Olde-Rikkert, Marcel; Huell, Michael

2009-01-01

Background A recent Dutch mono-centre randomised controlled trial has shown that occupational therapy improves daily functioning in dementia. The aim of this present study is to compare the effects of the Dutch community occupational therapy programme with a community occupational therapy consultation on daily functioning in older people with mild or moderate dementia and their primary caregivers in a German multi-centre context. Methods/Design A multi-centre single blind randomised controlled trial design is being used in seven health care centres (neurological, psychiatric and for older people) in urban regions. Patients are 1:1 randomised to treatment or control group. Assessors are blind to group assignment and perform measurements on both groups at baseline, directly after intervention at 6 weeks and at 16, 26 and 52 weeks follow-up. A sample of 140 community dwelling older people (aged >65 years) with mild or moderate dementia and their primary caregivers is planned. The experimental intervention consists of an evidence-based community occupational therapy programme including 10 sessions occupational therapy at home. The control intervention consists of one community occupational therapy consultation based on information material of the Alzheimer Society. Providers of both interventions are occupational therapists experienced in treatment of cognitively impaired older people and trained in both programmes. 'Community' indicates that occupational therapy intervention occurs in the person's own home. The primary outcome is patients' daily functioning assessed with the performance scale of the Interview for Deterioration in Daily Living Activities in Dementia and video tapes of daily activities rated by external raters blind to group assignment using the Perceive, Recall, Plan and Perform System of Task Analysis. Secondary outcomes are patients' and caregivers' quality of life, mood and satisfaction with treatment; the caregiver's sense of competence, caregiver's diary (medication, resource utilisation, time of informal care); and the incidence of long-term institutionalisation. Process evaluation is performed by questionnaires and focus group discussion. Discussion The transfer from the Dutch mono-centre design to the pragmatic multi-site trial in a German context implicates several changes in design issues including differences in recruitment time, training of interventionists and active control group treatment. The study is registered under DRKS00000053 at the German register of clinical trials, which is connected to the International Clinical Trials Registry Platform. PMID:19799779

Assessment of community-level effects of intermittent preventive treatment for malaria in schoolchildren in Jinja, Uganda (START-IPT trial): a cluster-randomised trial.

PubMed

Staedke, Sarah G; Maiteki-Sebuguzi, Catherine; Rehman, Andrea M; Kigozi, Simon P; Gonahasa, Samuel; Okiring, Jaffer; Lindsay, Steve W; Kamya, Moses R; Chandler, Clare I R; Dorsey, Grant; Drakeley, Chris

2018-06-01

Intermittent preventive treatment (IPT) is a well established malaria control intervention. Evidence that delivering IPT to schoolchildren could provide community-level benefits is limited. We did a cluster-randomised controlled trial to assess the effect of IPT of primary schoolchildren with dihydroartemisinin-piperaquine (DP) on indicators of malaria transmission in the community, in Jinja, Uganda. We included 84 clusters, each comprising one primary school and the 100 closest available households. The clusters were randomly assigned 1:1 to receive IPT with DP or standard care (control) by restricted randomisation to ensure balance by geography and school type. Children in intervention schools received IPT monthly for up to six rounds (June to December, 2014). We did cross-sectional community surveys in randomly selected households at baseline and in January to April, 2015, during which we measured participants' temperatures and obtained finger-prick blood smears for measurement of parasite prevalence by microscopy. We also did entomological surveys 1 night per month in households from 20 randomly selected IPT and 20 control clusters. The primary trial outcome was parasite prevalence in the final community survey. The primary entomological survey outcome was the annual entomological inoculation rate (aEIR) from July, 2014, to April, 2015. This trial is registered at ClinicalTrials.gov, number NCT02009215. Among 23 280 students registered in the 42 intervention schools, 10 079 (43%) aged 5-20 years were enrolled and received at least one dose of DP. 9286 (92%) of 10 079 received at least one full course of DP (three doses). Community-level parasite prevalence was lower in the intervention clusters than in the control clusters (19% vs 23%, adjusted risk ratio 0·85, 95% CI 0·73-1·00, p=0·05). The aEIR was lower in the intervention group than in the control group, but not significantly so (10·1 vs 15·2 infective bites per person, adjusted incidence rate ratio 0·80, 95% CI 0·36-1·80, p=0·59). IPT of schoolchildren with DP might have a positive effect on community-level malaria indicators and be operationally feasible. Studies with greater IPT coverage are needed. UK Medical Research Council, UK Department for International Development, and Wellcome Trust. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin, and school performance.

PubMed

Taylor-Robinson, David C; Maayan, Nicola; Soares-Weiser, Karla; Donegan, Sarah; Garner, Paul

2015-07-23

The World Health Organization (WHO) recommends treating all school children at regular intervals with deworming drugs in areas where helminth infection is common. As the intervention is often claimed to have important health, nutrition, and societal effects beyond the removal of worms, we critically evaluated the evidence on benefits. To summarize the effects of giving deworming drugs to children to treat soil-transmitted helminths on weight, haemoglobin, and cognition; and the evidence of impact on physical well-being, school attendance, school performance, and mortality. We searched the Cochrane Infectious Diseases Group Specialized Register (14 April 2015); Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library (2015, Issue 4); MEDLINE (2000 to 14 April 2015); EMBASE (2000 to 14 April 2015); LILACS (2000 to 14 April 2015); the metaRegister of Controlled Trials (mRCT); and reference lists, and registers of ongoing and completed trials up to 14 April 2015. We included randomized controlled trials (RCTs) and quasi-RCTs comparing deworming drugs for soil-transmitted helminths with placebo or no treatment in children aged 16 years or less, reporting on weight, haemoglobin, and formal tests of intellectual development. We also sought data on school attendance, school performance, and mortality. We included trials that combined health education with deworming programmes. At least two review authors independently assessed the trials, evaluated risk of bias, and extracted data. We analysed continuous data using the mean difference (MD) with 95% confidence intervals (CIs). Where data were missing, we contacted trial authors. We used outcomes at time of longest follow-up. The evidence quality was assessed using GRADE. This edition of the Cochrane Review adds the DEVTA trial from India, and draws on an independent analytical replication of a trial from Kenya. We identified 45 trials, including nine cluster-RCTs, that met the inclusion criteria. One trial evaluating mortality included over one million children, and the remaining 44 trials included a total of 67,672 participants. Eight trials were in children known to be infected, and 37 trials were carried out in endemic areas, including areas of high (15 trials), moderate (12 trials), and low prevalence (10 trials). Treating children known to be infectedTreating children known to be infected with a single dose of deworming drugs (selected by screening, or living in areas where all children are infected) may increase weight gain over the next one to six months (627 participants, five trials, low quality evidence). The effect size varied across trials from an additional 0.2 kg gain to 1.3 kg. There is currently insufficient evidence to know whether treatment has additional effects on haemoglobin (247 participants, two trials, very low quality evidence); school attendance (0 trials); cognitive functioning (103 participants, two trials, very low quality evidence), or physical well-being (280 participants, three trials, very low quality evidence). Community deworming programmesTreating all children living in endemic areas with a dose of deworming drugs probably has little or no effect on average weight gain (MD 0.04 kg less, 95% CI 0.11 kg less to 0.04 kg more; trials 2719 participants, seven trials, moderate quality evidence), even in settings with high prevalence of infection (290 participants, two trials). A single dose also probably has no effect on average haemoglobin (MD 0.06 g/dL, 95% CI -0.05 lower to 0.17 higher; 1005 participants, three trials, moderate quality evidence), or average cognition (1361 participants, two trials, low quality evidence).Similiarly, regularly treating all children in endemic areas with deworming drugs, given every three to six months, may have little or no effect on average weight gain (MD 0.08 kg, 95% CI 0.11 kg less to 0.27 kg more; 38,392 participants, 10 trials, low quality evidence). The effects were variable across trials; one trial from a low prevalence setting carried out in 1995 found an increase in weight, but nine trials carried out since then found no effect, including five from moderate and high prevalence areas.There is also reasonable evidence that regular treatment probably has no effect on average height (MD 0.02 cm higher, 95% CI 0.14 lower to 0.17 cm higher; 7057 participants, seven trials, moderate quality evidence); average haemoglobin (MD 0.02 g/dL lower; 95% CI 0.08 g/dL lower to 0.04 g/dL higher; 3595 participants, seven trials, low quality evidence); formal tests of cognition (32,486 participants, five trials, moderate quality evidence); exam performance (32,659 participants, two trials, moderate quality evidence); or mortality (1,005,135 participants, three trials, low quality evidence). There is very limited evidence assessing an effect on school attendance and the findings are inconsistent, and at risk of bias (mean attendance 2% higher, 95% CI 4% lower to 8% higher; 20,243 participants, two trials, very low quality evidence).In a sensitivity analysis that only included trials with adequate allocation concealment, there was no evidence of any effect for the main outcomes. Treating children known to have worm infection may have some nutritional benefits for the individual. However, in mass treatment of all children in endemic areas, there is now substantial evidence that this does not improve average nutritional status, haemoglobin, cognition, school performance, or survival.

Transabdominal amnioinfusion for improving fetal outcomes after oligohydramnios secondary to preterm prelabour rupture of membranes before 26 weeks.

PubMed

Van Teeffelen, Stijn; Pajkrt, Eva; Willekes, Christine; Van Kuijk, Sander M J; Mol, Ben Willem J

2013-08-03

Preterm prelabour rupture of membranes (PPROM) before 26 weeks can delay lung development and can cause pulmonary hypoplasia, as a result of oligohydramnios. Restoring the amniotic fluid volume by transabdominal amnioinfusion might prevent abnormal lung development and might have a protective effect for neurological complications, fetal deformities and neonatal sepsis. To assess the effectiveness of transabdominal amnioinfusion in improving perinatal outcome in women with oligohydramnios secondary to rupture of fetal membranes before 26 weeks. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013). All randomised controlled trials comparing transabdominal amnioinfusion with no transabdominal amnioinfusion. Cluster- or quasi-randomised trials were not eligible for inclusion. In cases where only an abstract was available, we attempted to find the full articles. Two review authors assessed trials for inclusion. No eligible trials were identified. There are no included studies. There is currently no evidence to evaluate the use of transabdominal amnioinfusion in women with oligohydramnios secondary to rupture of fetal membranes before 26 weeks for improving perinatal outcome. Further research examining the effects of this intervention is needed. Two randomised controlled trials are ongoing but final data have not yet been published.

Effect of Glycemic Index of Breakfast on Energy Intake at Subsequent Meal among Healthy People: A Meta-Analysis

PubMed Central

Sun, Feng-Hua; Li, Chunxiao; Zhang, Yan-Jie; Wong, Stephen Heung-Sang; Wang, Lin

2016-01-01

Meals with low glycemic index (GI) may suppress short-term appetite and reduce subsequent food intake compared with high-GI meals. However, no meta-analysis has been conducted to synthesize the evidence. This meta-analytic study was conducted to assess the effect of high- and low-GI breakfast on subsequent short-term food intake. Trials were identified through MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled trials, and manual searches of bibliographies until May 2015. Randomized controlled and cross-over trials comparing the effect of low- with high-GI breakfast on subsequent energy intake among healthy people were included. Nine studies consisting of 11 trials met the inclusion criteria. Only one trial was classified with high methodological quality. A total of 183 participants were involved in the trials. The meta-analytic results revealed no difference in breakfast GI (high-GI vs. low-GI) on subsequent short-term energy intake. In conclusion, it seems that breakfast GI has no effect on short-term energy intake among healthy people. However, high quality studies are still warranted to provide more concrete evidence. PMID:26742058

Resorbable versus titanium plates for orthognathic surgery.

PubMed

Agnihotry, Anirudha; Fedorowicz, Zbys; Nasser, Mona; Gill, Karanjot S

2017-10-04

Recognition of some of the limitations of titanium plates and screws used for the fixation of bones has led to the development of plates manufactured from bioresorbable materials. Whilst resorbable plates appear to offer clinical advantages over metal plates in orthognathic surgery, concerns remain about the stability of fixation and the length of time required for their degradation and the possibility of foreign body reactions. This review compares the use of titanium versus bioresorbable plates in orthognathic surgery and is an update of the Cochrane Review first published in 2007. To compare the effects of bioresorbable fixation systems with titanium systems used during orthognathic surgery. Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 20 January 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 11) in the Cochrane Library (searched 20 January 2017); MEDLINE Ovid (1946 to 20 January 2017); and Embase Ovid (1980 to 20 January 2017). We searched the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (clinicaltrials.gov; searched 20 January 2017), and the World Health Organization International Clinical Trials Registry Platform (searched 20 January 2017) for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Randomised controlled trials comparing bioresorbable versus titanium fixation systems used for orthognathic surgery in adults. Two review authors independently screened the results of the electronic searches, extracted data and assessed the risk of bias of the included studies. We resolved disagreement by discussion. Clinical heterogeneity between the included trials precluded pooling of data, and only a descriptive summary is presented. This review included two trials, involving 103 participants, one comparing titanium with resorbable plates and screws and the other titanium with resorbable screws. Both studies were at high risk of bias and provided very limited data for the primary outcomes of this review. All participants in one trial suffered mild to moderate postoperative discomfort with no statistically significant difference between the two plating groups at different follow-up times. Mean scores of patient satisfaction were 7.43 to 8.63 (range 0 to 10) with no statistically significant difference between the two groups throughout follow-up. Adverse effects reported in one study were two plate exposures in each group occurring between the third and ninth months. Plate exposures occurred mainly in the posterior maxillary region, except for one titanium plate exposure in the mandibular premolar region. Known causes of infection were associated with loosened screws and wound dehiscence with no statistically significant difference in the infection rate between titanium (3/196), and resorbable (3/165) plates. We do not have sufficient evidence to determine if titanium plates or resorbable plates are superior for fixation of bones after orthognathic surgery. This review provides insufficient evidence to show any difference in postoperative pain and discomfort, level of patient satisfaction, plate exposure or infection for plate and screw fixation using either titanium or resorbable materials.

Insufficient evidence for effectiveness of any treatment for oral lichen planus.

PubMed

Keenan, Analia Veitz; Ferraiolo, Debra

2011-01-01

The Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Embase databases were searched with no restrictions regarding language or date of publication. Bibliographies of identified publications were also checked for relevant studies, and authors were contacted to identify missing and unreported trials. The WHO International Trials Registry Platform was searched for ongoing studies, using the term 'oral lichen planus'. Randomised controlled clinical trials (RCTs) of therapy for symptomatic OLP which compared treatment with a placebo or between treatments or no intervention were considered for this review. The titles and abstracts of all reports identified were scanned independently by two review authors. All studies meeting the inclusion criteria were assessed for risk of bias and data were extracted. For dichotomous outcomes, the estimates of effects for the intervention were expressed as risk ratios (RR) together with 95% confidence intervals. For continuous outcomes, mean differences (MD) and 95% confidence intervals were used to summarise the data. Meta-analyses were conducted for studies with similar comparisons reporting the same outcome measures. Twenty-eight trials were included. Although topical steroids are considered first line treatment for symptomatic OLP, we identified no RCTs that compared steroids with placebo. There is no evidence from the three trials of pimecrolimus that this treatment is better than placebo in reducing pain from OLP. There is weak evidence from two trials, at unclear and high risk of bias respectively, that aloe vera may be associated with a reduction in pain compared to placebo, but it was not possible to pool the pain data from these trials. There is weak and unreliable evidence from two small trials, at high risk of bias, that cyclosporin may reduce pain and clinical signs of OLP, but meta-analysis of these trials was not possible.There were five trials that compared steroids with calcineurin inhibitors, each evaluating a different pair of interventions. There is no evidence from these trials that there is a difference between treatment with steroids compared to calcineurin inhibitors with regard to reducing pain associated with OLP. From six trials there is no evidence that any specific steroid therapy is more or less effective at reducing pain compared to another type or dose of steroid. From the 28 trials included in this systematic review, the wide range of interventions compared means there is insufficient evidence to support the effectiveness of any specific treatment as being superior.

Steroids for symptom control in infectious mononucleosis.

PubMed

Rezk, Emtithal; Nofal, Yazan H; Hamzeh, Ammar; Aboujaib, Muhammed F; AlKheder, Mohammad A; Al Hammad, Muhammad F

2015-11-08

Infectious mononucleosis, also known as glandular fever or the kissing disease, is a benign lymphoproliferative disorder. It is a viral infection caused by the Epstein-Barr virus (EBV), a ubiquitous herpes virus that is found in all human societies and cultures. Epidemiological studies show that over 95% of adults worldwide have been infected with EBV. Most cases of symptomatic infectious mononucleosis occur between the ages of 15 and 24 years. It is transmitted through close contact with an EBV shedder, contact with infected saliva or, less commonly, through sexual contact, blood transfusions or by sharing utensils; however, transmission actually occurs less than 10% of the time. Precautions are not needed to prevent transmission because of the high percentage of seropositivity for EBV. Infectious mononucleosis is self-limiting and typically lasts for two to three weeks. Nevertheless, symptoms can last for weeks and occasionally months.Symptoms include fever, lymphadenopathy, pharyngitis, hepatosplenomegaly and fatigue. Symptom relief and rest are commonly recommended treatments. Steroids have been used for their anti-inflammatory effects, but there are no universal criteria for their use. The objectives of the review were to determine the efficacy and safety of steroid therapy versus placebo, usual care or different drug therapies for symptom control in infectious mononucleosis. For this 2015 update we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (January 1966 to August 2015) and EMBASE (January 1974 to August 2015). We also searched trials registries, however we did not identify any new relevant completed or ongoing trials for inclusion. We combined the MEDLINE search with the Cochrane search strategy for identifying randomised controlled trials (RCTs). We adapted the search terms when searching EMBASE. RCTs comparing the effectiveness of steroids with placebo, usual care, or other interventions for symptom control for people with documented infectious mononucleosis. We used the standard methodological procedures expected by Cochrane. For this 2015 update, we did not identify any new RCTs for inclusion. The previous version of the review included seven trials with a total of 362 participants. Four trials compared the effectiveness of a steroid to placebo for short-term symptom control in glandular fever, one to aspirin, and two trials explored the effects of steroids in conjunction with an antiviral. Heterogeneity between trials prevented a combined analysis.Trials under-reported methodological design features. Three trials did not adequately describe sequence generation for randomisation. Four trials provided adequate details of allocation concealment. All trials were double-blind but four were not specific as to who was blinded. Loss to follow-up was under-reported in four trials, making it difficult to exclude attrition bias. The risk of selective reporting in the included trials was unclear.Across the trials, no benefit was found in 8/10 assessments of health improvement. Two trials found benefit of steroid therapy over placebo in reducing sore throat at 12 hours (eight-day course odds ratio (OR) 21.00, 95% confidence interval (CI) 1.94 to 227.20; one-dose OR 4.20, 95% CI 1.08 to 16.32), but the benefit was not maintained.In combination with an antiviral drug, participants in the steroid group had less pharyngeal discomfort between days two to four (OR 0.31, 95% CI 0.09 to 1.08) compared to placebo. Across the trials the effects on other common symptoms were less clear. Two trials set out to measure safety; they documented no major adverse effects. In two other trials adverse events were reported, including respiratory distress and acute onset of diabetes. However, the association of the events with the steroid is not definite. There is insufficient evidence to the efficacy of steroids for symptom control in infectious mononucleosis. There is a lack of research on the side effects and long-term complications.

Study protocol of the CAREST-trial: a randomised controlled trial on the (cost-) effectiveness of a CBT-based online self-help training for fear of cancer recurrence in women with curatively treated breast cancer.

PubMed

van Helmondt, Sanne Jasperine; van der Lee, Marije Liesbeth; de Vries, Jolanda

2016-07-25

One of the most prevalent long-term consequences of surviving breast cancer is fear of cancer recurrence (FCR), which is associated with higher (mental) healthcare costs and lower surveillance rates. The majority of breast cancer survivors report a need for professional help in dealing with FCR. An easy-accessible and cost-effective evidence-based psychological intervention for reducing FCR is lacking. In the current study an online self-help training to reduce FCR will be evaluated. In addition, the secondary aim of this study is to identify factors that predict whether women can benefit from the online self-help training or not. A multi-centre, parallel-groups, randomised controlled trial will be conducted to evaluate the (cost-) effectiveness of the CAREST-trial. A sample of 454 women with curatively treated breast cancer will be recruited from 8 hospitals in the Netherlands. Participants will be randomised to the intervention or usual care group (1:1). Self-report measures will be completed at baseline, 3 (post-intervention), 9, and 24 months. Primary outcome is FCR severity; secondary outcomes are healthcare costs, health status, and psychological distress. The online tailored self-help training "Less fear after cancer" is based on cognitive behavioural therapy and consists of 2 basic modules (psycho-education; basic principles of cognitive behavioural therapy) and 4 optional modules (rumination; action; relaxation; reassurance) to choose from. Each module consists of an informative part (texts, videos, audio files) and a practical part (exercises). For every patient, the intervention will be available for three months. Personal online support by an e-mail coach is available. Online self-help training may be an easy-accessible and cost-effective treatment to reduce the impact of FCR at an early stage in a large group of breast cancer survivors. A strength is the 24 months follow-up period in the health economic evaluation. The results of the study will provide information on the possible strengths and benefits of online self-help training for FCR in breast cancer survivors. This study is registered at the Netherlands Trial Register ( NTR4119 , date registered: August 15, 2013).

Effectiveness of a tailored intervention to improve cardiovascular risk management in primary care: study protocol for a randomised controlled trial.

PubMed

Huntink, Elke; Heijmans, Naomi; Wensing, Michel; van Lieshout, Jan

2013-12-17

Cardiovascular disease (CVD) is an important worldwide cause of mortality. In The Netherlands, CVD is the leading cause of death for women and the second cause of death for men. Recommendations for diagnosis and treatment of CVD are not well implemented in primary care. In this study, we aim to examine the effectiveness of a tailored implementation program targeted at practice nurses to improve healthcare for patients with (high risk for) CVD. A two-arm cluster randomized trial is planned. We offer practice nurses a tailored program to improve adherence to six specific recommendations related to blood pressure and cholesterol target values, risk profiling and lifestyle advice. Practice nurses are offered training and feedback on their motivational interviewing technique and an e-learning program on cardiovascular risk management (CVRM). They are also advised to screen for the presence and severity of depressive symptoms in patients. We also advise practice nurses to use selected E-health options (selected websites and Twitter-consult) in patients without symptoms of depression. Patients with mild depressive symptoms are referred to a physical exercise group. We recommend referring patients with major depressive symptoms for assessment and treatment of depressive symptoms if appropriate before starting CVRM. Data from 900 patients at high risk of CVD or with established CVD will be collected in 30 general practices in several geographical areas in The Netherlands. The primary outcome measure is performance of practice nurses in CVRM and reflects application of recommendations for personalized counselling and education of CVRM patients. Patients' health-related lifestyles (physical exercise, diet and smoking status) will be measured with validated questionnaires and medical record audit will be performed to document estimated CVD risk. Additionally, we will survey and interview participating healthcare professionals for exploration of processes of change. The control practices will provide usual care. Tailored interventions can improve healthcare. An understanding of the methods to reach the improved healthcare can be improved. This research contributes a share of it. Identification of the determinants of practice and developing implementation interventions were two steps which were completed. The subsequent step was implementation of the tailored intervention program. Name trial register: Nederlands trial register. Web address of trial register: http://www.trialregister.nl. Data of registration: 11 July 2013. Number of registration: NTR4069.

Minimally Invasive Ponto Surgery compared to the linear incision technique without soft tissue reduction for bone conduction hearing implants: study protocol for a randomized controlled trial.

PubMed

Calon, Tim G A; van Hoof, Marc; van den Berge, Herbert; de Bruijn, Arthur J G; van Tongeren, Joost; Hof, Janny R; Brunings, Jan Wouter; Jonhede, Sofia; Anteunis, Lucien J C; Janssen, Miranda; Joore, Manuela A; Holmberg, Marcus; Johansson, Martin L; Stokroos, Robert J

2016-11-09

Over the last years, less invasive surgical techniques with soft tissue preservation for bone conduction hearing implants (BCHI) have been introduced such as the linear incision technique combined with a punch. Results using this technique seem favorable in terms of rate of peri-abutment dermatitis (PAD), esthetics, and preservation of skin sensibility. Recently, a new standardized surgical technique for BCHI placement, the Minimally Invasive Ponto Surgery (MIPS) technique has been developed by Oticon Medical AB (Askim, Sweden). This technique aims to standardize surgery by using a novel surgical instrumentation kit and minimize soft tissue trauma. A multicenter randomized controlled trial is designed to compare the MIPS technique to the linear incision technique with soft tissue preservation. The primary investigation center is Maastricht University Medical Center. Sixty-two participants will be included with a 2-year follow-up period. Parameters are introduced to quantify factors such as loss of skin sensibility, dehiscence of the skin next to the abutment, skin overgrowth, and cosmetic results. A new type of sampling method is incorporated to aid in the estimation of complications. To gain further understanding of PAD, swabs and skin biopsies are collected during follow-up visits for evaluation of the bacterial profile and inflammatory cytokine expression. The primary objective of the study is to compare the incidence of PAD during the first 3 months after BCHI placement. Secondary objectives include the assessment of parameters related to surgery, wound healing, pain, loss of sensibility of the skin around the implant, implant extrusion rate, implant stability measurements, dehiscence of the skin next to the abutment, and esthetic appeal. Tertiary objectives include assessment of other factors related to PAD and a health economic evaluation. This is the first trial to compare the recently developed MIPS technique to the linear incision technique with soft tissue preservation for BCHI surgery. Newly introduced parameters and sampling method will aid in the prediction of results and complications after BCHI placement. Registered at the CCMO register in the Netherlands on 24 November 2014: NL50072.068.14 . Retrospectively registered on 21 April 2015 at ClinicalTrials.gov: NCT02438618 . This trial is sponsored by Oticon Medical AB.

Long-term effectiveness of mailed nicotine replacement therapy: study protocol of a randomized controlled trial 5-year follow-up.

PubMed

Kushnir, Vladyslav; Selby, Peter; Zawertailo, Laurie; Tyndale, Rachel F; Leatherdale, Scott T; Cunningham, John A

2017-07-18

Our group recently completed a randomized controlled trial, evaluating the efficacy of providing 5 weeks of free nicotine replacement therapy (NRT; in the form of the nicotine patch) by expedited postal mail without behavioral assistance to regular adult smokers interested in receiving it. The findings revealed that mailed provision of nicotine patches resulted in more than a doubling of quit rates at a six-month follow-up compared to a no intervention control group. While this trial provided evidence for the effectiveness of mailed nicotine patches in promoting cessation, the findings speak only to the short term effectiveness of this approach. As relapse to smoking is known to occur beyond the 6 month period, it is important to evaluate whether the net benefit of NRT in naturalistic settings can be maintained long-term. The present study aims to perform a 5-year follow-up survey of participants in the original trial to evaluate the long-term effectiveness of mailed NRT. Trained interviewers will contact participants in the randomized controlled trial 5 years post-enrollment. A total of 924 participants will be eligible to be contacted. Interviewers will first assess participants' smoking status and their level of nicotine dependence. Participants reporting not currently smoking will be asked whether they have smoked tobacco, even a puff, in the last 30 days (primary outcome measure: 30-day point prevalence abstinence), past 6 months (secondary outcome measure: prolonged 6-month abstinence), and since the 8-week follow-up survey (secondary outcome measure: > 4 year continuous abstinence). Interviewers will be blind to experimental condition at the time the primary outcome measure will be assessed. It is hypothesized that participants who received nicotine patches at baseline will display significantly higher quit rates at the 5-year follow-up as compared to participants who did not receive nicotine patches at baseline. If the study finds that the mailed distribution of free NRT is effective at promoting long-term cessation, it would provide further evidence to move forward with policies designed to make NRT treatment readily and freely available to smokers who request it. ClinicalTrials.gov : NCT01429129 , Registered 2 September 2011; NCT03097445 , Registered 25 March 2017.

Fluvoxamine versus other anti-depressive agents for depression

PubMed Central

Omori, Ichiro M; Watanabe, Norio; Nakagawa, Atsuo; Cipriani, Andrea; Barbui, Corrado; McGuire, Hugh; Churchill, Rachel; Furukawa, Toshi A

2014-01-01

Background Fluvoxamine, one of the oldest selective serotonin reuptake inhibitors (SSRIs), is prescribed to patients with major depression in many countries. Several studies have previously reviewed the efficacy and tolerability of fluvoxamine for the treatment of major depression. However, these reviews are now outdated. Objectives Our objective is to evaluate the effectiveness, tolerability and side effect profile of fluvoxamine for major depression in comparison with other anti-depressive agents, including tricyclics (TCAs), heterocyclics, other SSRIs, SNRIs, other newer agents and other conventional psychotropic drugs. Search methods We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register. Trial databases and ongoing trial registers in North America, Europe, Japan and Australia, were handsearched for randomised controlled trials. We checked reference lists of the articles included in the review, previous systematic reviews and major textbooks of affective disorder for published reports and citations of unpublished research. The date of last search was 31 August 2008. Selection criteria We included all randomised controlled trials, published in any language, that compared fluvoxamine with any other active antidepressants in the acute phase treatment of major depression. Data collection and analysis Two independent review authors inspected citations and abstracts, obtained papers, extracted data and assessed the risk of bias of included studies. We analysed dichotomous data using odds ratios (ORs) and continuous data using the standardised mean difference (SMD). A random effects model was used to combine studies. Main results A total of 54 randomised controlled trials (n = 5122) were included. No strong evidence was found to indicate that fluvoxamine was either superior or inferior to other antidepressants regarding response, remission and tolerability. However, differing side effect profiles were evident, especially with regard to gastrointestinal side effects of fluvoxamine when compared to other antidepressants. For example, fluvoxamine was generally associated with a higher incidence of vomiting/nausea (versus imipramine, OR 2.23, CI 1.59 to 3.14; versus clomipramine, OR 2.13, CI 1.06 to 4.27; versus amitriptyline, OR 2.86, CI 1.31 to 2.63). Authors’ conclusions We found no strong evidence that fluvoxamine was either superior or inferior to any other antidepressants in terms of efficacy and tolerability in the acute phase treatment of depression. However, differing side effect profiles were evident. Based on these findings, we conclude that clinicians should focus on practical or clinically relevant considerations, including these differences in side effect profiles. PMID:20238342

The impact of active stakeholder involvement on recruitment, retention and engagement of schools, children and their families in the cluster randomised controlled trial of the Healthy Lifestyles Programme (HeLP): a school-based intervention to prevent obesity.

PubMed

Lloyd, J; McHugh, C; Minton, J; Eke, H; Wyatt, K

2017-08-14

Recruitment and retention of participants is crucial for statistical power and internal and external validity and participant engagement is essential for behaviour change. However, many school-based interventions focus on programme content rather than the building of supportive relationships with all participants and tend to employ specific standalone strategies, such as incentives, to improve retention. We believe that actively involving stakeholders in both intervention and trial design improves recruitment and retention and increases the chances of creating an effective intervention. The Healthy Lifestyles Programme, HeLP (an obesity prevention programme for children 9-10 years old) was developed using intervention mapping and involved extensive stakeholder involvement in both the design of the trial and the intervention to ensure that: (i) delivery methods were suitably engaging, (ii) deliverers had the necessary skills and qualities to build relationships and (iii) the intervention dovetailed with the National Curriculum. HeLP was a year-long intervention consisting of 4 multi-component phases using a range of delivery methods. We recruited 1324 children from 32 schools from the South West of England to a cluster-randomised controlled trial to determine the effectiveness of HeLP in preventing obesity. The primary outcome was change in body mass index standard deviation score (BMI SDS) at 24 months post randomisation. Secondary outcomes included additional anthropometric and behavioural (physical activity and diet) measures at 18 and 24 months. Anthropometric and behavioural measures were taken in 99%, 96% and 94% of children at baseline, 18 and 24 months, respectively, with no differential follow up between the control and intervention groups at each time point. All children participated in the programme and 92% of children and 77% of parents across the socio-economic spectrum were considered to have actively engaged with HeLP. We attribute our excellent retention and engagement results to the high level of stakeholder involvement in both trial and intervention design, the building of relationships using appropriate personnel and creative delivery methods that are accessible to children and their families across the social spectrum. International Standard Randomised Controlled Trials Register, ISRCTN15811706 . Registered on 1 May 2012.

Increasing organ donation via anticipated regret (INORDAR): protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Throughout the world there is an insufficient supply of donor organs to meet the demand for organ transplantations. This paper presents a protocol for a randomised controlled trial, testing whether a simple, theory-based anticipated regret manipulation leads to a significant increase in posthumous organ donor registrations. Methods We will use a between-groups, prospective randomised controlled design. A random sample of 14,520 members of the adult Scottish general public will be contacted via post. These participants will be randomly allocated into 1 of the 4 conditions. The no questionnaire control (NQC) group will simply receive a letter and donor registration form. The questionnaire control (QC) arm will receive a questionnaire measuring their emotions and non-cognitive affective attitudes towards organ donation. The theory of planned behavior (TPB) group will complete the emotions and affective attitudes questionnaire plus additional items assessing their cognitive attitudes towards organ donation, perceived control over registration and how they think significant others view this action. Finally, the anticipated regret (AR) group will complete the same indices as the TPB group, plus two additional anticipated regret items. These items will assess the extent to which the participant anticipates regret for not registering as an organ donor in the near future. The outcome variable will be NHS Blood and Transplant verified registrations as an organ donor within 6 months of receiving our postal intervention. Discussion This study will assess whether simply asking people to reflect on the extent to which they may anticipate regret for not registering as an organ donor increases organ donor registration 6 months later. If successful, this simple and easy to administer theory-based intervention has the potential to save lives and money for the NHS by reducing the number of people receiving treatments such as dialysis. This intervention may also be incorporated into future organ donor campaigns. Trial registration number ISRCTN: ISRCTN92204897 PMID:22401534

Interventions for treating schistosomiasis mansoni.

PubMed

Saconato, H; Atallah, A

2000-01-01

Schistosomiasis is a parasite that is carried by freshwater snails. The intestinal form infects the intestine, liver and spleen and can be fatal. The objective of this review was to assess the effects of oxamniquine or praziquantel for treating Schistosomiasis mansoni We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Lilacs and reference lists of articles. The Revista da Sociedade Brasileira de Medicina Tropical and Brazilian Tropical Medicine Congress abstracts were handsearched Randomised and quasi-randomised trials comparing oxamniquine and/or praziquantel to placebo for the treatment of Schistosomiasis mansoni. Two reviewers independently assessed trial quality and extracted data. Thirteen trials met the inclusion criteria. Praziquantel and oxamniquine were effective in curing Schistosoma mansoni infection when compared to placebo. In Africa, praziquantel 40 mg/Kg is more effective than oxamniquine 15 mg/Kg in individuals older than 14 years (OR 3.54, 95%CI 1.70, 7.38), but no difference was found when compared with oxamniquine 30 mg/Kg (OR 0.29, 95%CI 0.08, 1.01). In Brazil, praziquantel was equally effective when compared with oxamniquine in individuals older than 14 years (OR 1.70, 95%CI 0.83, 3.49). Both drugs appear safe. There was no difference in reinfection rate between zinc supplementation and placebo (OR 0.82, 95%CI 0.47, 1.41). IPraziquantel and oxamniquine both appear to be effective for the treatment of Schistosomiasis mansoni, although lower doses of oxamniquine (less than 30 milligrams per kilogram) may not be as effective.

Interventions in the workplace to support breastfeeding for women in employment.

PubMed

Abdulwadud, Omar A; Snow, Mary Elizabeth

2012-10-17

In recent years there has been a rise in the participation rate of women in employment. Some may become pregnant while in employment and subsequently deliver their babies. Most may decide to return early to work after giving birth for various reasons. Unless these mothers get support from their employers and fellow employees, they might give up breastfeeding when they return to work. As a result, the duration and exclusivity of breastfeeding to the recommended age of the babies would be affected.Workplace environment can play a positive role to promote breastfeeding. For women going back to work, various types of workplace support interventions are available and this should not be ignored by employers. Notably, promoting breastfeeding in a workplace may have benefits for the women, the baby and also the employer. To assess the effectiveness of workplace interventions to support and promote breastfeeding among women returning to paid work after the birth of their children, and its impact on process outcomes pertinent to employees and employers. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (2 August 2012). Two authors independently assessed all identified studies for randomised controlled trials and quasi-randomised controlled trials that compared workplace interventions with no intervention or two or more workplace interventions against each other. Two authors planned to evaluate the methodological quality of the eligible trials and extract data. There were no randomised controlled trials or quasi-randomised controlled trials identified. No trials have evaluated the effectiveness of workplace interventions in promoting breastfeeding among women returning to paid work after the birth of their child. The impact of such intervention on process outcomes is also unknown. Randomised controlled trials are required to establish the benefits of various types of workplace interventions to support, encourage and promote breastfeeding among working mothers.

Bar versus ball attachments for implant-supported overdentures in complete edentulism: A systematic review.

PubMed

Anas El-Wegoud, Marwah; Fayyad, Ahmed; Kaddah, Amal; Nabhan, Ashraf

2018-04-01

Implant-supported overdenture is one of the most predictable treatment options used in complete edentulism. However, differences have been reported between bar and ball attachments used to retain overdentures in terms of patient satisfaction and prosthesis retention. The purpose of this study is to compare the effectiveness of bar and ball attachments for conventionally loaded implant-supported overdentures in completely edentulous patients to improve patient satisfaction and prosthesis retention. We conducted the review according to the Cochrane methods and following MECIR standards. We searched Cochrane Oral Health Group Trial register, Cochrane Central Register of Controlled Trials, MEDLINE, and the WHO ICTRP (March 31, 2017). Two review authors assessed trials for inclusion and risk of bias, extracted data, and checked for accuracy. We have expressed results as risk ratio or mean differences, together with their 95% confidence intervals. We included 10 trials (465 participants). After 5 y, one trial reported higher patient satisfaction when bar attachment was used (MD 1.30, 95% CI 0.20-2.40), and reported no difference between both systems in prosthesis retention (MD -0.90, 95% CI -1.90 to 0.10). Two trials reported no implant failures after 1 and 5 y in both attachments. Downgrading of evidence was based on the unclear risk of bias of included studies and the wide CI crossing the line of no effect. There is insufficient evidence to support bar or ball attachment to be used with implant-supported overdentures in completely edentulous patients to improve patient satisfaction and prosthesis retention (PROSPERO 2014:CRD42014014594). © 2017 Wiley Periodicals, Inc.

Corticosteroids for Bell's palsy (idiopathic facial paralysis).

PubMed

Madhok, Vishnu B; Gagyor, Ildiko; Daly, Fergus; Somasundara, Dhruvashree; Sullivan, Michael; Gammie, Fiona; Sullivan, Frank

2016-07-18

Inflammation and oedema of the facial nerve are implicated in causing Bell's palsy. Corticosteroids have a potent anti-inflammatory action that should minimise nerve damage. This is an update of a review first published in 2002 and last updated in 2010. To determine the effectiveness and safety of corticosteroid therapy in people with Bell's palsy. On 4 March 2016, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS. We reviewed the bibliographies of the randomised trials and contacted known experts in the field to identify additional published or unpublished trials. We also searched clinical trials registries for ongoing trials. Randomised trials and quasi-randomised trials comparing different routes of administration and dosage schemes of corticosteroid or adrenocorticotrophic hormone therapy versus a control group receiving no therapy considered effective for this condition, unless the same therapy was given in a similar way to the experimental group. We used standard Cochrane methodology. The main outcome of interest was incomplete recovery of facial motor function (i.e. residual facial weakness). Secondary outcomes were cosmetically disabling persistent sequelae, development of motor synkinesis or autonomic dysfunction (i.e. hemifacial spasm, crocodile tears) and adverse effects of corticosteroid therapy manifested during follow-up. We identified seven trials, with 895 evaluable participants for this review. All provided data suitable for the primary outcome meta-analysis. One of the trials was new since the last version of this Cochrane systematic review. Risk of bias in the older, smaller studies included some unclear- or high-risk assessments, whereas we deemed the larger studies at low risk of bias. Overall, 79/452 (17%) participants allocated to corticosteroids had incomplete recovery of facial motor function six months or more after randomisation; significantly fewer than the 125/447 (28%) in the control group (risk ratio (RR) 0.63, 95% confidence interval (CI) 0.50 to 0.80, seven trials, n = 895). The number of people who need to be treated with corticosteroids to avoid one incomplete recovery was 10 (95% CI 6 to 20). The reduction in the proportion of participants with cosmetically disabling sequelae six months after randomisation was very similar in the corticosteroid and placebo groups (RR 0.96, 95% CI 0.40 to 2.29, two trials, n = 75, low-quality evidence). However, there was a significant reduction in motor synkinesis during follow-up in participants receiving corticosteroids (RR 0.64, 95% CI 0.45 to 0.91, three trials, n = 485, moderate-quality evidence). Three studies explicitly recorded the absence of adverse effects attributable to corticosteroids. One trial reported that three participants receiving prednisolone had temporary sleep disturbances and two trials gave a detailed account of adverse effects occurring in 93 participants, all non-serious; the combined analysis of data from these three trials found no significant difference in adverse effect rates between people receiving corticosteroids and people receiving placebo (RR 1.04, 95% CI 0.71 to 1.51, n = 715). The available moderate- to high-quality evidence from randomised controlled trials showed significant benefit from treating Bell's palsy with corticosteroids.

A meta-analysis of randomized controlled trials of azilsartan therapy for blood pressure reduction.

PubMed

Takagi, Hisato; Mizuno, Yusuke; Niwa, Masao; Goto, Shin-Nosuke; Umemoto, Takuya

2014-05-01

Although there have been a number of azilsartan trials, no meta-analysis of the findings has been conducted to date. We performed the first meta-analysis of randomized controlled trials of azilsartan therapy for the reduction of blood pressure (BP) in patients with hypertension. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched from the beginning of the records through March 2013 using web-based search engines (PubMed and OVID). Eligible studies were prospective randomized controlled trials of azilsartan (including azilsartan medoxomil) vs. any control therapy that reported clinic or 24-h mean BP as an outcome. For each study, data for the changes from baseline to final clinic systolic BP (SBP) and diastolic BP (DBP) in both the azilsartan group and the control group were used to generate mean differences and 95% confidence intervals (CIs). Of 27 potentially relevant articles screened initially, 7 reports of randomized trials of azilsartan or azilsartan medoxomil therapy enrolling a total of 6152 patients with hypertension were identified and included. Pooled analysis suggested a significant reduction in BP changes among patients randomized to 40 mg of azilsartan vs. control therapy (clinic SBP: -4.20 mm Hg; 95% CI: -6.05 to -2.35 mm Hg; P<0.00001; clinic DBP: -2.58 mm Hg; 95% CI: -3.69 to -1.48 mm Hg; P<0.00001; 24-h mean SBP: -3.33 mm Hg; 95% CI: -4.74 to -1.93 mm Hg; P<0.00001; 24-h mean DBP: -2.12 mm Hg; 95% CI: -2.74 to -1.49 mm Hg; P<0.00001). In conclusion, azilsartan therapy appears to provide a greater reduction in BP than control therapy in patients with hypertension.

Nutritional supplements for people being treated for active tuberculosis.

PubMed

Grobler, Liesl; Nagpal, Sukrti; Sudarsanam, Thambu D; Sinclair, David

2016-06-29

Tuberculosis and malnutrition are linked in a complex relationship. Tuberculosis may cause undernutrition through increased metabolic demands and decreased intake, and nutritional deficiencies may worsen the disease, or delay recovery by depressing important immune functions. At present, there is no evidence-based nutritional guidance for adults and children being treated for tuberculosis. To assess the effects of oral nutritional supplements in people being treated with antituberculous drug therapy for active tuberculosis. We searched the Cochrane Infectious Disease Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, 2016), MEDLINE (from 1946 to 4 February 2016), EMBASE (from 1980 to 4 February 2016), LILACS (from 1982 to 4 February 2016), the metaRegister of Controlled Trials (mRCT), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and the Indian Journal of Tuberculosis up to 4 February 2016, and checked the reference lists of all included studies. Randomized controlled trials that compared any oral nutritional supplement given for at least four weeks with no nutritional intervention, placebo, or dietary advice only for people being treated for active tuberculosis. The primary outcomes of interest were all-cause death, and cure at six and 12 months. Two review authors independently selected trials for inclusion, and extracted data and assessed the risk of bias in the included trials. We presented the results as risk ratios (RR) for dichotomous variables, and mean differences (MD) for continuous variables, with 95% confidence intervals (CIs). Where appropriate, we pooled data from trials with similar interventions and outcomes. We assessed the quality of the evidence using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Thirty-five trials, including 8283 participants, met the inclusion criteria of this review. Macronutrient supplementationSix trials assessed the provision of free food, or high-energy supplements. Only two trials measured total dietary intake, and in both trials the intervention increased calorie consumption compared to controls.The available trials were too small to reliably prove or exclude clinically important benefits on mortality (RR 0.34, 95% CI 0.10 to 1.20; four trials, 567 participants, very low quality evidence), cure (RR 0.91, 95% CI 0.59 to 1.41; one trial, 102 participants, very low quality evidence), or treatment completion (data not pooled; two trials, 365 participants, very low quality evidence).Supplementation probably produces a modest increase in weight gain during treatment for active tuberculosis, although this was not seen consistently across all trials (data not pooled; five trials, 883 participants, moderate quality evidence). Two small studies provide some evidence that quality of life may also be improved but the trials were too small to have much confidence in the result (data not pooled; two trials, 134 participants, low quality evidence). Micronutrient supplementationSix trials assessed multi-micronutrient supplementation in doses up to 10 times the dietary reference intake, and 18 trials assessed single or dual micronutrient supplementation.Routine multi-micronutrient supplementation may have little or no effect on mortality in HIV-negative people with tuberculosis (RR 0.86, 95% CI 0.46 to 1.6; four trials, 1219 participants, low quality evidence), or HIV-positive people who are not taking antiretroviral therapy (RR 0.92, 95% CI 0.69 to 1.23; three trials, 1429 participants, moderate quality evidence). There is insufficient evidence to know if supplementation improves cure (no trials), treatment completion (RR 0.99, 95% CI 0.95 to 1.04; one trial, 302 participants, very low quality evidence), or the proportion of people who remain sputum positive during the first eight weeks (RR 0.92, 95% CI 0.63 to 1.35; two trials, 1020 participants, very low quality evidence). However, supplementation may have little or no effect on weight gain during treatment (data not pooled; five trials, 2940 participants, low quality evidence), and no studies have assessed the effect on quality of life.Plasma levels of vitamin A appear to increase following initiation of tuberculosis treatment regardless of supplementation. In contrast, supplementation probably does improve plasma levels of zinc, vitamin D, vitamin E, and selenium, but this has not been shown to have clinically important benefits. Of note, despite multiple studies of vitamin D supplementation in different doses, statistically significant benefits on sputum conversion have not been demonstrated. There is currently insufficient research to know whether routinely providing free food, or energy supplements improves tuberculosis treatment outcomes, but it probably improves weight gain in some settings.Although blood levels of some vitamins may be low in people starting treatment for active tuberculosis, there is currently no reliable evidence that routinely supplementing above recommended daily amounts has clinical benefits.

A systematic review of randomised controlled trials on the effectiveness of exercise programs on Lumbo Pelvic Pain among postnatal women.

PubMed

Tseng, Pei-Ching; Puthussery, Shuby; Pappas, Yannis; Gau, Meei-Ling

2015-11-26

A substantial number of women tend to be affected by Lumbo Pelvic Pain (LPP) following child birth. Physical exercise is indicated as a beneficial method to relieve LPP, but individual studies appear to suggest mixed findings about its effectiveness. This systematic review aimed to synthesise evidence from randomised controlled trials on the effectiveness of exercise on LPP among postnatal women to inform policy, practice and future research. A systematic review was conducted of all randomised controlled trials published between January 1990 and July 2014, identified through a comprehensive search of following databases: PubMed, PEDro, Embase, Cinahl, Medline, SPORTDiscus, Cochrane Pregnancy and Childbirth Group's Trials Register, and electronic libraries of authors'institutions. Randomised controlled trials were eligible for inclusion if the intervention comprised of postnatal exercise for women with LPP onset during pregnancy or within 3 months after delivery and the outcome measures included changes in LPP. Selected articles were assessed using the PEDro Scale for methodological quality and findings were synthesised narratively as meta-analysis was found to be inappropriate due to heterogeneity among included studies. Four randomised controlled trials were included, involving 251 postnatal women. Three trials were rated as of 'good' methodological quality. All trials, except one, were at low risk of bias. The trials included physical exercise programs with varying components, differing modes of delivery, follow up times and outcome measures. Intervention in one trial, involving physical therapy with specific stabilising exercises, proved to be effective in reducing LPP intensity. An improvement in gluteal pain on the right side was reported in another trial and a significant difference in pain frequency in another. Our review indicates that only few randomised controlled trials have evaluated the effectiveness of exercise on LPP among postnatal women. There is also a great amount of variability across existing trials in the components of exercise programs, modes of delivery, follow up times and outcome measures. While there is some evidence to indicate the effectiveness of exercise for relieving LPP, further good quality trials are needed to ascertain the most effective elements of postnatal exercise programs suited for LPP treatment.

Effectiveness of a self-management intervention with personalised genetic and lifestyle-related risk information on coronary heart disease and diabetes-related risk in type 2 diabetes (CoRDia): study protocol for a randomised controlled trial.

PubMed

Davies, Anna K; McGale, Nadine; Humphries, Steve E; Hirani, Shashivadan P; Beaney, Katherine E; Bappa, Dauda A S; McCabe, John G; Newman, Stanton P

2015-12-02

Many patients with type 2 diabetes fail to achieve good glycaemic control. Poor control is associated with complications including coronary heart disease (CHD). Effective self-management and engagement in health behaviours can reduce risks of complications. However, patients often struggle to adopt and maintain these behaviours. Self-management interventions have been found to be effective in improving glycaemic control. Recent developments in the field of genetics mean that patients can be given personalised information about genetic- and lifestyle-associated risk of developing CHD. Such information may increase patients' motivation to engage in self-management. The Coronary Risk in Diabetes (CoRDia) trial will compare the effectiveness of a self-management intervention, with and without provision of personalised genetic- and lifestyle-associated risk information, with usual care, on clinical and behavioural outcomes, the cognitive predictors of behaviour, and psychological wellbeing. Participants will be adults aged 25-74 years registered with general practices in the East of England, diagnosed with type 2 diabetes, with no history of heart disease, and with a glycated haemoglobin level of ≥6.45% (47 mmol/mol). Consenting participants will be randomised to one of three arms: usual care control, group self-management only, group self-management plus personalised genetic- and lifestyle-associated risk information. The self-management groups will receive four weekly 2-hour group sessions, focusing on knowledge and information sharing, problem solving, goal setting and action planning to promote medication adherence, healthy eating, and physical activity. Primary outcomes are glycaemic control and CHD risk. Clinical data will be collected from GP records, including HbA1c, weight, body mass index, blood pressure, and HDL and total cholesterol. Self-reported health behaviours, including medication adherence, healthy eating and physical activity, and cognitive outcomes will be assessed by questionnaire. Measures will be taken at baseline, 3 months (questionnaire only), 6 months and 12 months post-baseline. This study will determine whether the addition of personalised genetic- and lifestyle-associated CHD risk information to a group self-management intervention improves diabetes control and CHD risk compared with group self-management and usual care. Effectiveness of the combined intervention on health behaviours cognitions theorised to predict them, and psychological outcomes will also be investigated. This study has been registered at ClinicalTrials.gov; registration identifier NCT01891786 , registered 28 June 2013.

Antibiotic prophylaxis for surgical site infection in people undergoing liver transplantation.

PubMed

Almeida, Ricardo A M B; Hasimoto, Claudia N; Kim, Anna; Hasimoto, Erica N; El Dib, Regina

2015-12-05

Surgical site infection is more frequent in liver transplantation than in other types of solid organ transplantation with different antibiotics. Studies have shown that the rate of surgical site infection varies from 8.8% to 37.5% after liver transplantation. Therefore, antimicrobial prophylaxis is likely an essential tool for reducing these infections. However, the literature lacks evidence indicating the best prophylactic antibiotic regimen that can be used for liver transplantation. To assess the benefits and harms of antibiotic prophylactic regimens for surgical site infection in people undergoing liver transplantation. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded and Latin American Caribbean Health Sciences Literature (LILACS). The most recent search was performed on 11 September 2015. All eligible randomised clinical trials comparing any antibiotic regimen versus placebo, versus no intervention or versus another antibiotic regimen for surgical site infection in liver transplant recipients, regardless of age, sex and reason for transplantation. Quasi-randomised studies and other observational studies were considered for data on harm if retrieved with search results for randomised clinical trials. Two review authors selected relevant trials, assessed risk of bias of studies and extracted data. The electronic search identified 786 publications after removal of duplicates. From this search, only one seemingly randomised clinical trial, published in abstract form, fulfilled the inclusion criteria of this review. This trial was conducted at Shiraz Transplant Centre, Shiraz, Iran, where investigators randomly assigned a total of 180 consecutive liver transplant recipients. We judged the overall risk of bias of the trial published in abstract form as high. Researchers reported no numerical data but mentioned that 163 participants met the inclusion criteria after randomisation, and hence were included in the analyses. Most probably, the 17 excluded participants were high-risk liver transplant recipients. Trial authors concluded that they could find no differences between the two antibiotic regimens - ceftriaxone plus metronidazole versus ampicillin-sulbactam plus ceftizoxime - when given to liver transplant recipients. Review authors could not reconfirm the analyses because, as it has been mentioned, trial authors provided no trial data for analyses. Benefits and harms of antibiotic prophylactic regimens for surgical site infection in liver transplantation remain unclear. Additional well-conducted randomised clinical trials adhering to SPIRIT (Spirit Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) guidelines are needed to determine the exact role of antibiotic prophylactic regimens in patients undergoing liver transplantation.

Management of faecal incontinence and constipation in adults with central neurological diseases.

PubMed

Coggrave, M; Wiesel, P H; Norton, C

2006-04-19

People with neurological disease have a much higher risk of both faecal incontinence and constipation than the general population. There is often a fine line between the two conditions, with any management intended to ameliorate one risking precipitating the other. Bowel problems are observed to be the cause of much anxiety and may reduce quality of life in these people. Current bowel management is largely empirical with a limited research base. To determine the effects of management strategies for faecal incontinence and constipation in people with neurological diseases affecting the central nervous system. We searched the Cochrane Incontinence Group Specialised Trials Register (searched 26 January 2005), the Cochrane Central Register of Controlled Trials (Issue 2, 2005), MEDLINE (January 1966 to May 2005), EMBASE (January 1998 to May 2005) and all reference lists of relevant articles. All randomised or quasi-randomised trials evaluating any types of conservative or surgical measure for the management of faecal incontinence and constipation in people with neurological diseases were selected. Specific therapies for the treatment of neurological diseases that indirectly affect bowel dysfunction were also considered. Two reviewers assessed the methodological quality of eligible trials and two reviewers independently extracted data from included trials using a range of pre-specified outcome measures. Ten trials were identified by the search strategy, most were small and of poor quality. Oral medications for constipation were the subject of four trials. Cisapride does not seem to have clinically useful effects in people with spinal cord injuries (three trials). Psyllium was associated with increased stool frequency in people with Parkinson's disease but did not alter colonic transit time (one trial). Prucalopride, an enterokinetic did not demonstrate obvious benefits in this patient group (one study). Some rectal preparations to initiate defaecation produced faster results than others (one trial). Different time schedules for administration of rectal medication may produce different bowel responses (one trial). Mechanical evacuation may be more effective than oral or rectal medication (one trial). There appears to be a benefit to patients in one-off educational interventions from nurses. The clinical significance of any of these results is difficult to interpret. There is still remarkably little research on this common and, to patients, very significant condition. It is not possible to draw any recommendation for bowel care in people with neurological diseases from the trials included in this review. Bowel management for these people must remain empirical until well-designed controlled trials with adequate numbers and clinically relevant outcome measures become available.

Setting the stage for chronic health problems: cumulative childhood adversity among homeless adults with mental illness in Vancouver, British Columbia.

PubMed

Patterson, Michelle L; Moniruzzaman, Akm; Somers, Julian M

2014-04-12

It is well documented that childhood abuse, neglect and household dysfunction are disproportionately present in the backgrounds of homeless adults, and that these experiences adversely impact child development and a wide range of adult outcomes. However, few studies have examined the cumulative impact of adverse childhood experiences on homeless adults with mental illness. This study examines adverse events in childhood as predictors of duration of homelessness, psychiatric and substance use disorders, and physical health in a sample of homeless adults with mental illness. This study was conducted using baseline data from a randomized controlled trial in Vancouver, British Columbia for participants who completed the Adverse Childhood Experiences (ACE) scale at 18 months follow-up (n=364). Primary outcomes included current mental disorders; substance use including type, frequency and severity; physical health; duration of homelessness; and vocational functioning. In multivariable regression models, ACE total score independently predicted a range of mental health, physical health, and substance use problems, and marginally predicted duration of homelessness. Adverse childhood experiences are overrepresented among homeless adults with complex comorbidities and chronic homelessness. Our findings are consistent with a growing body of literature indicating that childhood traumas are potent risk factors for a number of adult health and psychiatric problems, particularly substance use problems. Results are discussed in the context of cumulative adversity and self-trauma theory. This trial has been registered with the International Standard Randomized Control Trial Number Register and assigned ISRCTN42520374.

Study of ecologo-biological reactions of common flax to finely dispersed metallurgical wastes

NASA Astrophysics Data System (ADS)

Zakharova, O.; Gusev, A.; Skripnikova, E.; Skripnikova, M.; Krutyakov, Yu; Kudrinsky, A.; Mikhailov, I.; Senatova, S.; Chuprunov, C.; Kuznetsov, D.

2015-11-01

Study was carried out on the influence of metallurgic industrial sludge on morphometric and biochemical indicators as well as productivity of common flax under laboratory and field conditions. In laboratory settings negative influence on seed germinating ability and positive influence on sprouts biomass production in water medium were observed. In sand medium suppression of biological productivity under the influence of sludge together with photosynthetic system II (FS II) activity stimulation were registered. Biochemical study showed peroxidase activity decrease in laboratory, while activity of polyphenol oxidase, superoxide dismutase and catalase were given a mild boost under the influence of sludge. In the field trial, positive influence of sludge on flax photosynthetic apparatus was shown. Positive influence of sludge on vegetation and yield indicators was observed. The analysis of heavy metals content showed excess over maximum allowable concentration (MAC) of copper and zinc in control plants, it may point to the background soil pollution. In the plants from the trial groups receiving 0.5 and 2 ton/ha heavy metals content below the control values was registered. Application of 4 ton/ha led to the maximum content of copper and zinc in the plants among the trial groups. The analysis of soils from the test plots indicated no excess over maximum allowable concentrations of heavy metals. Thus, further study of possibilities of using metallurgic industrial sludge as a soil stimulator in flax cultivation at the application rate of 0.5 t/ha seems promising.

CTRI – Clicking to greater transparency and accountability

PubMed Central

George, Bobby

2012-01-01

A clinical trial registry (CTR) is an official platform for registering a clinical trial (CT) with an objective of providing increased transparency and access to CTs to the public at large. Clinical Trials Registry - India (CTRI) is a free online public record system for registration of CTs being conducted in India. The vision of the CTRI is to ensure that every CT conducted in the region is prospectively registered with full disclosure of the trial data set items. With more number of CTs being conducted in the country, with a large number being global multicentre trials, it is binding on the industry/investigators/sponsor to comply with the requirements laid down. While there are pros and cons, there is enough scope for improvement of CTRI. PMID:23293758

Clinical trials in rheumatoid arthritis: a status report from the ClinicalTrials.gov website.

PubMed

Paul, Jisna R; Ranganathan, Prabha

2012-06-01

The aims of this study are to describe the characteristics of clinical trials in rheumatoid arthritis (RA) listed in ClinicalTrials.gov and examine existing trends in study design, funding sources, outcomes, and drugs under investigation. We conducted a survey of ongoing clinical trials in RA registered in the ClinicalTrials.gov website. We used the advanced search option and applied the following inclusion criteria, "rheumatoid arthritis", "open studies", "interventional", and "adults 18 years or older". Of 127 eligible trials, 53.5% of the studies were either phase 3 or 4, and 40.2% were phase 1, 2, and 2/3. Two-thirds of the trials were randomized (70.9%), and over half were, in addition, double-blinded (53.5%) and placebo-controlled (53.5%). Universities were listed as the primary sponsor for 18.9% of the trials and pharmaceutical industry for 73.2%. Majority of the trials were multi-center studies (93%) conducted outside the United States (54.3%). The most frequently used endpoint was drug efficacy (54.3%) followed by drug safety (25.2%). Most industry-funded trials were open for less than 12 months, whereas most university-funded trials were open for more than 24 months (58% each). Biologic therapies were the focus of most trials in the registry (78.5%). Randomized, double-blinded, placebo-controlled, phase 3 and 4 trials form the majority of ongoing clinical trials in RA. The preponderance of industry funding of RA trials and the short duration of such trials are troubling trends which need to be addressed.

Parent training support for intellectually disabled parents.

PubMed

Coren, Esther; Hutchfield, Jemeela; Thomae, Manuela; Gustafsson, Carina

2010-06-16

Intellectual disability may impact on an individual's capacity to parent a child effectively. Research suggests that the number of intellectually disabled people with children is increasing. Children of parents with intellectual disabilities may be at increased risk of neglectful care which could lead to health, developmental and behavioural problems, or increased risk of intellectual disability.However, there is some indication that some parents with intellectual disabilities are able to provide adequate child care if they are given appropriate training and support to do so. To assess the effectiveness of parent training interventions to support the parenting of parents with intellectual disabilities We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, EMBASE, CINAHL, PsycINFO, ASSIA, Sociological Abstracts, Dissertation Abstracts International, MetaRegister of Controlled Trials, and ZETOC. Randomised controlled trials comparing parent training interventions for parents with intellectual disabilities with usual care or with a control group. Outcomes of interest were: the attainment of parenting skills specific to the intervention, safe home practices and the understanding of child health. Two review authors independently assessed risk of bias and undertook data extraction. Three trials met the inclusion criteria for this review but no meta-analysis was possible. One study reported improved maternal-child interaction following group parent training compared with the control group. The second study reported some improvements in parents knowledge of life threatening emergencies, ability to recognise dangers and identify precautions and smaller improvements in their ability to implement precautions, use medicines safely and recognise child illness and symptoms. The third study reported improvement in child care and safety skills following the intervention. There is some risk of bias in the included studies, with limited information available to assess possible bias and to fully assess the findings of one included study. Whilst the evidence presented here does seem promising with regard to the ability of such interventions to improve parenting knowledge and skill in this population, there is a need for larger RCTs of interventions before conclusions can be drawn about the effectiveness of parent training for this group of parents.

Mosquito larval source management for controlling malaria

PubMed Central

Tusting, Lucy S; Thwing, Julie; Sinclair, David; Fillinger, Ulrike; Gimnig, John; Bonner, Kimberly E; Bottomley, Christian; Lindsay, Steven W

2015-01-01

Background Malaria is an important cause of illness and death in people living in many parts of the world, especially sub-Saharan Africa. Long-lasting insecticide treated bed nets (LLINs) and indoor residual spraying (IRS) reduce malaria transmission by targeting the adult mosquito vector and are key components of malaria control programmes. However, mosquito numbers may also be reduced by larval source management (LSM), which targets mosquito larvae as they mature in aquatic habitats. This is conducted by permanently or temporarily reducing the availability of larval habitats (habitat modification and habitat manipulation), or by adding substances to standing water that either kill or inhibit the development of larvae (larviciding). Objectives To evaluate the effectiveness of mosquito LSM for preventing malaria. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; CABS Abstracts; and LILACS up to 24 October 2012. We handsearched the Tropical Diseases Bulletin from 1900 to 2010, the archives of the World Health Organization (up to 11 February 2011), and the literature database of the Armed Forces Pest Management Board (up to 2 March 2011). We also contacted colleagues in the field for relevant articles. Selection criteria We included cluster randomized controlled trials (cluster-RCTs), controlled before-and-after trials with at least one year of baseline data, and randomized cross-over trials that compared LSM with no LSM for malaria control. We excluded trials that evaluated biological control of anopheline mosquitoes with larvivorous fish. Data collection and analysis At least two authors assessed each trial for eligibility. We extracted data and at least two authors independently determined the risk of bias in the included studies. We resolved all disagreements through discussion with a third author. We analyzed the data using Review Manager 5 software. Main results We included 13 studies; four cluster-RCTs, eight controlled before-and-after trials, and one randomized cross-over trial. The included studies evaluated habitat modification (one study), habitat modification with larviciding (two studies), habitat manipulation (one study), habitat manipulation plus larviciding (two studies), or larviciding alone (seven studies) in a wide variety of habitats and countries. Malaria incidence In two cluster-RCTs undertaken in Sri Lanka, larviciding of abandoned mines, streams, irrigation ditches, and rice paddies reduced malaria incidence by around three-quarters compared to the control (RR 0.26, 95% CI 0.22 to 0.31, 20,124 participants, two trials, moderate quality evidence). In three controlled before-and-after trials in urban and rural India and rural Kenya, results were inconsistent (98,233 participants, three trials, very low quality evidence). In one trial in urban India, the removal of domestic water containers together with weekly larviciding of canals and stagnant pools reduced malaria incidence by three quarters. In one trial in rural India and one trial in rural Kenya, malaria incidence was higher at baseline in intervention areas than in controls. However dam construction in India, and larviciding of streams and swamps in Kenya, reduced malaria incidence to levels similar to the control areas. In one additional randomized cross-over trial in the flood plains of the Gambia River, where larval habitats were extensive and ill-defined, larviciding by ground teams did not result in a statistically significant reduction in malaria incidence (2039 participants, one trial). Parasite prevalence In one cluster-RCT from Sri Lanka, larviciding reduced parasite prevalence by almost 90% (RR 0.11, 95% CI 0.05 to 0.22, 2963 participants, one trial, moderate quality evidence). In five controlled before-and-after trials in Greece, India, the Philippines, and Tanzania, LSM resulted in an average reduction in parasite prevalence of around two-thirds (RR 0.32, 95% CI 0.19 to 0.55, 8041 participants, five trials, moderate quality evidence). The interventions in these five trials included dam construction to reduce larval habitats, flushing of streams, removal of domestic water containers, and larviciding. In the randomized cross-over trial in the flood plains of the Gambia River, larviciding by ground teams did not significantly reduce parasite prevalence (2039 participants, one trial). Authors’ conclusions In Africa and Asia, LSM is another policy option, alongside LLINs and IRS, for reducing malaria morbidity in both urban and rural areas where a sufficient proportion of larval habitats can be targeted. Further research is needed to evaluate whether LSM is appropriate or feasible in parts of rural Africa where larval habitats are more extensive. PMID:23986463

Variation in outcomes of the Melbourne Infant, Feeding, Activity and Nutrition Trial (InFANT) Program according to maternal education and age.

PubMed

Cameron, Adrian J; Ball, Kylie; Hesketh, Kylie D; McNaughton, Sarah A; Salmon, Jo; Crawford, David A; Lioret, Sandrine; Campbell, Karen J

2014-01-01

To assess the effectiveness of the Melbourne Infant Feeding, Activity and Nutrition Trial (InFANT) Program according to maternal education and age. A cluster-randomised controlled trial involving 542 mother/infant pairs from 62 existing first-time parent groups was conducted in 2008 in Melbourne, Australia. The intervention involved 6 × 2-hour dietitian-delivered sessions, DVD and written resources from infant age 4-15 months. Outcomes included infant diet (3 × 24 h diet recalls), physical activity (accelerometry), television viewing and body mass index. We tested for moderation by maternal education (with/without a University degree) and age (< 32 and ≥ 32 years). The trial was registered with the ISRCTN Register (identifier 81847050). Interaction effects with the treatment arm were observed for maternal education and age. The intervention effects on vegetable (positive effect) and sweet snack consumption (negative effect) were greater in children with higher educated mothers while intervention effects on water consumption (positive effect) were greater in infants with lower educated mothers. The intervention was also more effective in increasing both vegetable and water consumption in infants with mothers aged < 32 years. Child obesity prevention interventions may be differentially effective according to maternal education and age. Evidence of differential effects is important for informing more sensitively targeted/tailored approaches. © 2013.

Laser-assisted in-situ keratomileusis (LASIK) versus photorefractive keratectomy (PRK) for myopia.

PubMed

Shortt, Alex J; Allan, Bruce D S; Evans, Jennifer R

2013-01-31

Myopia (also known as short-sightedness or near-sightedness) is an ocular condition in which the refractive power of the eye is greater than is required, resulting in light from distant objects being focused in front of the retina instead of directly on it. The two most commonly used surgical techniques to permanently correct myopia are photorefractive keratectomy (PRK) and laser-assisted in-situ keratomileusis (LASIK). To compare the effectiveness and safety of LASIK and PRK for correction of myopia by examining post-treatment uncorrected visual acuity, refractive outcome, loss of best spectacle-corrected visual acuity, pain scores, flap complications in LASIK, subepithelial haze, adverse events, quality of life indices and higher order aberrations. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 11), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2012), EMBASE (January 1980 to November 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 15 November 2012. We also searched the reference lists of the studies and the Science Citation Index. We included randomised controlled trials comparing LASIK and PRK for the correction of any degree of myopia. Two authors independently assessed trial quality and extracted data. We summarised data using the odds ratio and mean difference. We combined odds ratios using a random-effects model after testing for heterogeneity. We included 13 trials (1135 participants, 1923 eyes) in this review. Nine of these trials randomised eyes to treatment, two trials randomised people to treatment and treated both eyes, and two trials randomised people to treatment and treated one eye. None of the paired trials reported an appropriate paired analysis. We considered the overall quality of evidence to be low for most outcomes because of the risk of bias in the included trials. There was evidence that LASIK gives a faster visual recovery than PRK and is a less painful technique. Results at one year after surgery were comparable: most analyses favoured LASIK but they were not statistically significant. LASIK gives a faster visual recovery and is a less painful technique than PRK. The two techniques appear to give similar outcomes one year after surgery. Further trials using contemporary techniques are required to determine whether LASIK and PRK as currently practised are equally safe. Randomising eyes to treatment is an efficient design, but only if analysed properly. In future trials, more efforts could be made to mask the assessment of outcome.

Stroke liaison workers for stroke patients and carers: an individual patient data meta-analysis.

PubMed

Ellis, Graham; Mant, Jonathan; Langhorne, Peter; Dennis, Martin; Winner, Simon

2010-05-12

Many patients experience depression, social isolation and anxiety post stroke. These are associated with a poorer outcome. Ameliorating these problems may improve patient wellbeing. To evaluate the impact of a healthcare worker or volunteer whose multi-dimensional roles have been grouped under the title 'stroke liaison worker'. We searched the Cochrane Stroke Group Trials Register (searched February 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2009), MEDLINE (1966 to 2009), EMBASE (1980 to 2009) and four other databases. We performed a cited reference search, searched conference proceedings and trials registers, checked reference lists and contacted authors and trial investigators. Randomised controlled trials investigating the impact of a stroke liaison worker versus usual care. We invited trialists to participate in a review of individual patient data. Primary outcomes for patients were subjective health status and extended activities of daily living. Primary outcomes for carers were subjective health status including measures of carer strain. We included 16 trials involving 4759 participants. Analysis did not show a significant overall difference for subjective health status (standardised mean difference (SMD) -0.03, 95% confidence interval (CI) -0.11 to 0.04, P = 0.34) or extended activities of daily living (SMD 0.04, 95% CI -0.03 to 0.11, P = 0.22). There was no overall significant effect for the outcome of carer subjective health status (SMD 0.04, 95% CI -0.05 to 0.14, P = 0.37). Patients with mild to moderate disability (Barthel 15 to 19) had a significant reduction in dependence (odds ratio (OR) 0.62, 95% CI 0.44 to 0.87, P = 0.006). This would equate to 10 fewer dependent patients (95% CI 17 fewer to 4 fewer) for every 100 patients seen by the stroke liaison worker. Similar results were seen for the outcome of death or dependence for the subgroup with Barthel 15 to 19 (OR 0.55, 95% CI 0.38 to 0.81, P = 0.002). This risk difference equates to 11 fewer dead or dependent patients (95% CI 17 fewer to 4 fewer) for every 100 patients seen by the stroke liaison worker. There is no evidence for the effectiveness of this multifaceted intervention in improving outcomes for all groups of patients or carers. Patients with mild to moderate disability benefit from a reduction in death and disability. Patients and carers do report improved satisfaction with some aspects of service provision.

Ursodeoxycholic acid for cystic fibrosis-related liver disease.

PubMed

Cheng, Katharine; Ashby, Deborah; Smyth, Rosalind L

2014-12-15

Abnormal biliary secretion leads to the thickening of bile and the formation of plugs within the bile ducts; the consequent obstruction and abnormal bile flow ultimately results in the development of cystic fibrosis-related liver disease. This condition peaks in adolescence with up to 20% of adolescents with cystic fibrosis developing chronic liver disease. Early changes in the liver may ultimately result in end-stage liver disease with people needing transplantation. One therapeutic option currently used is ursodeoxycholic acid. To analyse evidence that ursodeoxycholic acid improves indices of liver function, reduces the risk of developing chronic liver disease and improves outcomes in general in cystic fibrosis. We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also contacted drug companies.Date of the most recent search of the Group's trials register: 29 May 2014. Randomised controlled trials of the use of ursodeoxycholic acid for at least three months compared with placebo or no additional treatment in people with cystic fibrosis. Two authors independently assessed trial eligibility and quality. Ten trials have been identified, of which three trials involving 118 participants were included; the dose of ursodeoxycholic acid ranged from 10 to 20 mg/kg/day for up to 12 months. The complex design used in two trials meant that data could only be analysed for subsets of participants. There was no significant difference in weight change, mean difference -0.90 kg (95% confidence interval -1.94 to 0.14) based on 30 participants from two trials. Improvement in biliary excretion was reported in only one trial and no significant change after treatment was shown. There were no data available for analysis for long-term outcomes such as death or need for liver transplantation. There are few trials assessing the effectiveness of ursodeoxycholic acid. There is insufficient evidence to justify its routine use in cystic fibrosis.

Participant recruitment and retention in longitudinal preconception randomized trials: lessons learnt from the Calcium And Pre-eclampsia (CAP) trial.

PubMed

Lawrie, Theresa A; Betrán, Ana Pilar; Singata-Madliki, Mandisa; Ciganda, Alvaro; Hofmeyr, G Justus; Belizán, José M; Purnat, Tina Dannemann; Manyame, Sarah; Parker, Catherine; Cormick, Gabriela

2017-10-26

The preconception period has the potential to influence pregnancy outcomes and randomized controlled trials (RCTs) are needed to evaluate a variety of potentially beneficial preconception interventions. However, RCTs commencing before pregnancy have significant participant recruitment and retention challenges. The Calcium And Pre-eclampsia trial (CAP trial) is a World Health Organization multi-country RCT of calcium supplementation commenced before pregnancy to prevent recurrent pre-eclampsia in which non-pregnant participants are recruited and followed up until childbirth. This sub-study explores recruitment methods and preconception retention of participants of the CAP trial to inform future trials. Recruiters at the study sites in Argentina, South Africa and Zimbabwe completed post-recruitment phase questionnaires on recruitment methods used. Qualitative data from these questionnaires and quantitative data on pre-pregnancy trial visit attendance and pregnancy rates up to September 2016 are reported in this paper. RStudio (Version 0.99.903 https://www.rstudio.org ) statistical software was used for summary statistics. Between July 2011 and 8 September 2016, 1354 women with previous pre-eclampsia were recruited. Recruitment took 2 years longer than expected and was facilitated mainly through medical record/register and maternity ward/clinic-based strategies. Recruiters highlighted difficulties associated with inadequate medical records, redundant patient contact details, and follow-up of temporarily ineligible women as some of the challenges faced. Whilst the attendance rates at pre-pregnancy visits were high (78% or more), visits often occurred later than scheduled. Forty-five percent of participants became pregnant (614/1354), 33.5% (454/1354) within 1 year of randomization. In preconception trials, both retrospective and prospective methods are useful for recruiting eligible women with certain conditions. However, these are time-consuming in low-resource settings with suboptimal medical records and other challenges. Trial planners should ensure that trial budgets cover sufficient on-site researchers with pre-trial training, and should consider using mobile phone and web-based electronic tools to optimize recruitment and retention. This should lead to greater efficiency and shorter trial durations. Pan-African Clinical Trials Registry, Registration Number: PACTR201105000267371 . The trial was registered on 6 December 2016.

Methods for specifying the target difference in a randomised controlled trial: the Difference ELicitation in TriAls (DELTA) systematic review.

PubMed

Hislop, Jenni; Adewuyi, Temitope E; Vale, Luke D; Harrild, Kirsten; Fraser, Cynthia; Gurung, Tara; Altman, Douglas G; Briggs, Andrew H; Fayers, Peter; Ramsay, Craig R; Norrie, John D; Harvey, Ian M; Buckley, Brian; Cook, Jonathan A

2014-05-01

Randomised controlled trials (RCTs) are widely accepted as the preferred study design for evaluating healthcare interventions. When the sample size is determined, a (target) difference is typically specified that the RCT is designed to detect. This provides reassurance that the study will be informative, i.e., should such a difference exist, it is likely to be detected with the required statistical precision. The aim of this review was to identify potential methods for specifying the target difference in an RCT sample size calculation. A comprehensive systematic review of medical and non-medical literature was carried out for methods that could be used to specify the target difference for an RCT sample size calculation. The databases searched were MEDLINE, MEDLINE In-Process, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Methodology Register, PsycINFO, Science Citation Index, EconLit, the Education Resources Information Center (ERIC), and Scopus (for in-press publications); the search period was from 1966 or the earliest date covered, to between November 2010 and January 2011. Additionally, textbooks addressing the methodology of clinical trials and International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) tripartite guidelines for clinical trials were also consulted. A narrative synthesis of methods was produced. Studies that described a method that could be used for specifying an important and/or realistic difference were included. The search identified 11,485 potentially relevant articles from the databases searched. Of these, 1,434 were selected for full-text assessment, and a further nine were identified from other sources. Fifteen clinical trial textbooks and the ICH tripartite guidelines were also reviewed. In total, 777 studies were included, and within them, seven methods were identified-anchor, distribution, health economic, opinion-seeking, pilot study, review of the evidence base, and standardised effect size. A variety of methods are available that researchers can use for specifying the target difference in an RCT sample size calculation. Appropriate methods may vary depending on the aim (e.g., specifying an important difference versus a realistic difference), context (e.g., research question and availability of data), and underlying framework adopted (e.g., Bayesian versus conventional statistical approach). Guidance on the use of each method is given. No single method provides a perfect solution for all contexts.

Oxcarbazepine versus carbamazepine monotherapy for partial onset seizures.

PubMed

Koch, Marcus W; Polman, Susanne Kl

2009-10-07

Partial onset seizures are often treated with the standard antiepileptic drug carbamazepine. Oxcarbazepine is a newer antiepileptic drug related to carbamazepine that is claimed to be better tolerated. To compare efficacy and tolerability of carbamazepine and oxcarbazepine monotherapy for partial onset seizures. We searched the Cochrane Epilepsy Group Specialised Register (4 August 2009), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library issue 3, 2009), MEDLINE (January 1966 to May 2008), reference lists of relevant articles and conference proceedings. We also contacted manufacturers and researchers in the field for published or unpublished data. Blinded and unblinded randomised controlled trials of carbamazepine versus oxcarbazepine monotherapy for partial onset seizures. Both authors independently assessed trial quality, according to the guidelines in the Cochrane Reviewer's Handbook, and extracted information about study population, type of intervention, outcome measures and study design. All analyses in this review are by intention-to-treat. We tested for statistical heterogeneity among the identified studies using the chi-squared test. Three trials (723 participants) were included. Only one trial used adequate outcome measures of efficacy; therefore, the results pertaining to efficacy are based on a single trial, whereas the results pertaining to adverse events are based on all three included trials. There was no overall difference in time to treatment withdrawal between the two drugs (hazard ratio (HR) of oxcarbazepine (OXC) versus carbamazepine (CBZ): 1.04, 95% confidence interval (CI) 0.78 to 1.39). Further analyses showed no significant difference in treatment withdrawal for unacceptable side effects (HR of OXC versus CBZ: 0.85, 95% CI 0.59 to 1.24) and in treatment withdrawal for inadequate seizure control (HR of OXC versus CBZ: 1.33, 95% CI 0.82 to 2.15). Oxcarbazepine and carbamazepine appeared to be similarly effective and well tolerated although the confidence intervals around estimates were wide and do not rule out the possibility of important differences existing. Significantly fewer patients on carbamazepine treatment developed nausea or vomiting, or both (odds ratio of OXC versus CBZ: 3.15, 95% CI 1.39 to 7.14). Oxcarbazepine and carbamazepine appear to be similarly effective and well tolerated. However, the possibility of important differences existing between these drugs cannot be ruled out.

Antenatal perineal massage for reducing perineal trauma.

PubMed

Beckmann, Michael M; Stock, Owen M

2013-04-30

Perineal trauma following vaginal birth can be associated with significant short-term and long-term morbidity. Antenatal perineal massage has been proposed as one method of decreasing the incidence of perineal trauma. To assess the effect of antenatal digital perineal massage on the incidence of perineal trauma at birth and subsequent morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (22 October 2012), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2012, Issue 10), PubMed (1966 to October 2012), EMBASE (1980 to October 2012) and reference lists of relevant articles. Randomised and quasi-randomised controlled trials evaluating any described method of antenatal digital perineal massage undertaken for at least the last four weeks of pregnancy. Both review authors independently applied the selection criteria, extracted data from the included studies and assessed study quality. We contacted study authors for additional information. We included four trials (2497 women) comparing digital perineal massage with control. All were of good quality. Antenatal digital perineal massage was associated with an overall reduction in the incidence of trauma requiring suturing (four trials, 2480 women, risk ratio (RR) 0.91 (95% confidence interval (CI) 0.86 to 0.96), number needed to treat to benefit (NNTB) 15 (10 to 36)) and women practicing perineal massage were less likely to have an episiotomy (four trials, 2480 women, RR 0.84 (95% CI 0.74 to 0.95), NNTB 21 (12 to 75)). These findings were significant for women without previous vaginal birth only. No differences were seen in the incidence of first- or second-degree perineal tears or third-/fourth-degree perineal trauma. Only women who have previously birthed vaginally reported a statistically significant reduction in the incidence of pain at three months postpartum (one trial, 376 women, RR 0.45 (95% CI 0.24 to 0.87) NNTB 13 (7 to 60)). No significant differences were observed in the incidence of instrumental deliveries, sexual satisfaction, or incontinence of urine, faeces or flatus for any women who practised perineal massage compared with those who did not massage. Antenatal digital perineal massage reduces the likelihood of perineal trauma (mainly episiotomies) and the reporting of ongoing perineal pain, and is generally well accepted by women. As such, women should be made aware of the likely benefit of perineal massage and provided with information on how to massage.

Protocol for a multi-centre randomised controlled trial comparing arthroscopic hip surgery to physiotherapy-led care for femoroacetabular impingement (FAI): the Australian FASHIoN trial.

PubMed

Murphy, Nicholas J; Eyles, Jillian; Bennell, Kim L; Bohensky, Megan; Burns, Alexander; Callaghan, Fraser M; Dickenson, Edward; Fary, Camdon; Grieve, Stuart M; Griffin, Damian R; Hall, Michelle; Hobson, Rachel; Kim, Young Jo; Linklater, James M; Lloyd, David G; Molnar, Robert; O'Connell, Rachel L; O'Donnell, John; O'Sullivan, Michael; Randhawa, Sunny; Reichenbach, Stephan; Saxby, David J; Singh, Parminder; Spiers, Libby; Tran, Phong; Wrigley, Tim V; Hunter, David J

2017-09-26

Femoroacetabular impingement syndrome (FAI), a hip disorder affecting active young adults, is believed to be a leading cause of hip osteoarthritis (OA). Current management approaches for FAI include arthroscopic hip surgery and physiotherapy-led non-surgical care; however, there is a paucity of clinical trial evidence comparing these approaches. In particular, it is unknown whether these management approaches modify the future risk of developing hip OA. The primary objective of this randomised controlled trial is to determine if participants with FAI who undergo hip arthroscopy have greater improvements in hip cartilage health, as demonstrated by changes in delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) index between baseline and 12 months, compared to those who undergo physiotherapy-led non-surgical management. This is a pragmatic, multi-centre, two-arm superiority randomised controlled trial comparing hip arthroscopy to physiotherapy-led management for FAI. A total of 140 participants with FAI will be recruited from the clinics of participating orthopaedic surgeons, and randomly allocated to receive either surgery or physiotherapy-led non-surgical care. The surgical intervention involves arthroscopic FAI surgery from one of eight orthopaedic surgeons specialising in this field, located in three different Australian cities. The physiotherapy-led non-surgical management is an individualised physiotherapy program, named Personalised Hip Therapy (PHT), developed by a panel to represent the best non-operative care for FAI. It entails at least six individual physiotherapy sessions over 12 weeks, and up to ten sessions over six months, provided by experienced musculoskeletal physiotherapists trained to deliver the PHT program. The primary outcome measure is the change in dGEMRIC score of a ROI containing both acetabular and femoral head cartilages at the chondrolabral transitional zone of the mid-sagittal plane between baseline and 12 months. Secondary outcomes include patient-reported outcomes and several structural and biomechanical measures relevant to the pathogenesis of FAI and development of hip OA. Interventions will be compared by intention-to-treat analysis. The findings will help determine whether hip arthroscopy or an individualised physiotherapy program is superior for the management of FAI, including for the prevention of hip OA. Australia New Zealand Clinical Trials Registry reference: ACTRN12615001177549 . Trial registered 2/11/2015 (retrospectively registered).

COMplex Fracture Orthopedic Rehabilitation (COMFORT) - Real-time visual biofeedback on weight bearing versus standard training methods in the treatment of proximal femur fractures in the elderly: study protocol for a multicenter randomized controlled trial.

PubMed

Raaben, Marco; Redzwan, Syaiful; Augustine, Robin; Blokhuis, Taco Johan

2018-04-12

Proximal femur fractures are a common injury after low energy trauma in the elderly. Most rehabilitation programs are based on restoring mobility and early resumption of weight-bearing. However, therapy compliance is low in patients following lower extremity fractures. Moreover, little is known about the relevance of gait parameters and how to steer the rehabilitation after proximal femur fractures in the elderly. Therefore, the aim of this prospective, randomized controlled trial is to gain insight in gait parameters and evaluate if real-time visual biofeedback can improve therapy compliance after proximal femur fractures in the elderly. This is a two-arm, parallel-design, prospective, randomized controlled trial. Inclusion criteria are age ≥ 60 years, a proximal femur fracture following low energy trauma, and unrestricted-weight bearing. Exclusion criteria are cognitive impairment and limited mobility before trauma. Participants are randomized into either the control group, which receives care as usual, or the intervention group, which receives real-time visual biofeedback about weight-bearing during gait in addition to care as usual. Spatiotemporal gait parameters will be measured in 94 participants per group during a 30-m walk with an ambulatory biofeedback system (SensiStep). The progress of rehabilitation will be evaluated by the primary outcome parameters maximum peak load and step duration in relation to the discharge date. Secondary outcome parameters include other spatiotemporal gait parameters in relation to discharge date. Furthermore, the gait parameters will be related to three validated clinical tests: Elderly Mobility Scale; Functional Ambulation Categories; and Visual Analogue Scale. The primary hypothesis is that participants in the intervention group will show improved and faster rehabilitation compared to the control group. The first aim of this multicenter trial is to investigate the normal gait patterns after proximal femur fractures in the elderly. The use of biofeedback systems during rehabilitation after proximal femur fractures in the elderly is promising; therefore, the second aim is to investigate the effect of real-time visual biofeedback on gait after proximal femur fractures in the elderly. This could lead to improved outcome. In addition, analysis of the population may indicate characteristics of subgroups that benefit from feedback, making a differentiated approach in rehabilitation strategy possible. TrialRegister.nl, NTR6794 . Registered on 31 October 2017.