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.

Diet and dietary supplement intervention trials for the prevention of prostate cancer recurrence: a review of the randomized controlled trial evidence.

PubMed

Van Patten, Cheri L; de Boer, Johan G; Tomlinson Guns, Emma S

2008-12-01

We review the effect of diet and dietary supplement interventions on prostate cancer progression, recurrence and survival. A literature search was conducted in MEDLINE, EMBASE and CINAHL to identify diet and dietary supplement intervention studies in men with prostate cancer using prostate specific antigen or prostate specific antigen doubling time as a surrogate serum biomarker of prostate cancer recurrence and/or survival. Of the 32 studies identified 9 (28%) were randomized controlled trials and the focus of this review. In these studies men had confirmed prostate cancer and elevated or increasing prostate specific antigen. Only 1 trial included men with metastatic disease. When body mass index was reported, men were overweight or obese. A significant decrease in prostate specific antigen was observed in some studies using a low fat vegan diet, soy beverage or lycopene supplement. While not often reported as an end point, a significant increase in prostate specific antigen doubling time was observed in a study on lycopene supplementation. In only 1 randomized controlled trial in men undergoing orchiectomy was a survival end point of fewer deaths with lycopene supplementation reported. A limited number of randomized controlled trials were identified in which diet and dietary supplement interventions appeared to slow disease progression in men with prostate cancer, although results vary. Studies were limited by reliance on the surrogate biomarker prostate specific antigen, sample size and study duration. Well designed trials are warranted to expand knowledge, replicate findings and further assess the impact of diet and dietary supplement interventions on recurrence and treatment associated morbidities.

Predictors of Study Attrition in a Randomized Controlled Trial Evaluating a Perinatal Home-Visiting Program with Mothers with Psychosocial Vulnerabilities

PubMed Central

Foulon, Stéphanie; Greacen, Tim; Pasquet, Blandine; Dugravier, Romain; Saïas, Thomas; Guedeney, Nicole; Guedeney, Antoine; Tubach, Florence

2015-01-01

Objective Randomised controlled trials evaluating perinatal home-visiting programs are frequently confronted with the problem of high attrition rates. The aim of the present study is to identify predictors of study attrition in a trial evaluating a perinatal home-visiting program in France. Materials and Methods CAPEDP is a French randomized trial comparing a perinatal home-visiting program using psychologists versus usual care (N = 440). The first assessment was at inclusion into the trial at the 27th week of pregnancy and the final assessment when the child reached the age of two. Attrition rates were calculated at 3 and 24 months postpartum. Stepwise logistic regression was used to identify predictors of early (between inclusion and 3 months postpartum) and later (between 3 and 24 months postpartum) attrition among social, psychological and parenting factors. Results Attrition rates were 17% and 63% at 3 and 24 months respectively. At 24 months, there was significantly more attrition in the control arm (70.6%) compared to the intervention arm (55.2%). Five independent predictors of early attrition were identified: having already had an abortion; having greater attachment insecurity as measured with the Vulnerable Attachment Style Questionnaire (VASQ); having lower global severity of psychiatric symptoms as assessed with the Symptom Check-List (SCL-90) at inclusion, being neither currently employed nor studying; and declaring no tobacco consumption during pregnancy. Being randomized into the control arm, having undergone early parental loss before age 11 and having lower global severity of psychiatric symptoms (SCL-90) at 3 months postpartum were the only variables associated with later attrition. Conclusion This study provides key information for identifying mothers who may require specific support to avoid study attrition in trials evaluating a home-visiting program. PMID:26554839

Publication status of contemporary oncology randomised controlled trials worldwide.

PubMed

Chen, Yu-Pei; Liu, Xu; Lv, Jia-Wei; Li, Wen-Fei; Zhang, Yuan; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Mao, Yan-Ping; Ma, Jun

2016-10-01

Little is known about the extent of selective publication in contemporary oncology randomised controlled trials (RCTs) worldwide. This study aimed to evaluate the rates of publication and timely publication (within 24 months) for contemporary oncology RCTs from all over the world. We also investigated the trial characteristics associated with publication and timely publication. We identified all phase III oncology RCTs registered on ClinicalTrials.gov with a primary completion date between January 2008 and December 2012. We searched PubMed and EMBASE to identify publications. The final search date was 31 December 2015. Our primary outcome measure was the time to publication from the primary completion date to the date of primary publication in a peer-reviewed journal. We identified 598 completed oncology RCTs; overall, 398 (66.6%) had been published. For published trials, the median time to publication was 25 months (interquartile range, 16-37 months). Only 192 trials (32.1%) were published within 24 months. Timely publication was independently associated with trials completed late in 2012. Trials conducted in Asia and other regions were less likely to have timely publication, but trials conducted in different locations were all equally likely to be published. Industry- and NIH-funded trials were equally likely to be published timely or at any time after trial completion. Among 391 published trials with clear primary outcomes, there was a trend for timely publication of positive trials compared with negative trials. Despite the ethical obligations and societal expectations of disclosing findings promptly, oncology RCTs performed poorly. Copyright © 2016 Elsevier Ltd. All rights reserved.

Placebo effects in psychiatry: mediators and moderators

PubMed Central

Weimer, Katja; Colloca, Luana; Enck, Paul

2015-01-01

A strong placebo response in psychiatric disorders has been noted for the past 50 years and various attempts have been made to identify predictors of it, by use of meta-analyses of randomised controlled trials and laboratory studies. We reviewed 31 meta-analyses and systematic reviews of more than 500 randomised placebo-controlled trials across psychiatry (depression, schizophrenia, mania, attention-deficit hyperactivity disorder, autism, psychosis, binge-eating disorder, and addiction) for factors identified to be associated with increased placebo response. Of 20 factors discussed, only three were often linked to high placebo responses: low baseline severity of symptoms, more recent trials, and unbalanced randomisation (more patients randomly assigned to drug than placebo). Randomised controlled trials in non-drug therapy have not added further predictors, and laboratory studies with psychological, brain, and genetic approaches have not been successful in identifying predictors of placebo responses. This comprehensive Review suggests that predictors of the placebo response are still to be discovered, the response probably has more than one mediator, and that different and distinct moderators are probably what cause the placebo response within psychiatry and beyond. PMID:25815249

Effect of cinnamon on glucose control and lipid parameters.

PubMed

Baker, William L; Gutierrez-Williams, Gabriela; White, C Michael; Kluger, Jeffrey; Coleman, Craig I

2008-01-01

To perform a meta-analysis of randomized controlled trials of cinnamon to better characterize its impact on glucose and plasma lipids. A systematic literature search through July 2007 was conducted to identify randomized placebo-controlled trials of cinnamon that reported data on A1C, fasting blood glucose (FBG), or lipid parameters. The mean change in each study end point from baseline was treated as a continuous variable, and the weighted mean difference was calculated as the difference between the mean value in the treatment and control groups. A random-effects model was used. Five prospective randomized controlled trials (n = 282) were identified. Upon meta-analysis, the use of cinnamon did not significantly alter A1C, FBG, or lipid parameters. Subgroup and sensitivity analyses did not significantly change the results. Cinnamon does not appear to improve A1C, FBG, or lipid parameters in patients with type 1 or type 2 diabetes.

Weight change in control group participants in behavioural weight loss interventions: a systematic review and meta-regression study

PubMed Central

2012-01-01

Background Unanticipated control group improvements have been observed in intervention trials targeting various health behaviours. This phenomenon has not been studied in the context of behavioural weight loss intervention trials. The purpose of this study is to conduct a systematic review and meta-regression of behavioural weight loss interventions to quantify control group weight change, and relate the size of this effect to specific trial and sample characteristics. Methods Database searches identified reports of intervention trials meeting the inclusion criteria. Data on control group weight change and possible explanatory factors were abstracted and analysed descriptively and quantitatively. Results 85 trials were reviewed and 72 were included in the meta-regression. While there was no change in control group weight, control groups receiving usual care lost 1 kg more than control groups that received no intervention, beyond measurement. Conclusions There are several possible explanations why control group changes occur in intervention trials targeting other behaviours, but not for weight loss. Control group participation may prevent weight gain, although more research is needed to confirm this hypothesis. PMID:22873682

Weight change in control group participants in behavioural weight loss interventions: a systematic review and meta-regression study.

PubMed

Waters, Lauren; George, Alexis S; Chey, Tien; Bauman, Adrian

2012-08-08

Unanticipated control group improvements have been observed in intervention trials targeting various health behaviours. This phenomenon has not been studied in the context of behavioural weight loss intervention trials. The purpose of this study is to conduct a systematic review and meta-regression of behavioural weight loss interventions to quantify control group weight change, and relate the size of this effect to specific trial and sample characteristics. Database searches identified reports of intervention trials meeting the inclusion criteria. Data on control group weight change and possible explanatory factors were abstracted and analysed descriptively and quantitatively. 85 trials were reviewed and 72 were included in the meta-regression. While there was no change in control group weight, control groups receiving usual care lost 1 kg more than control groups that received no intervention, beyond measurement. There are several possible explanations why control group changes occur in intervention trials targeting other behaviours, but not for weight loss. Control group participation may prevent weight gain, although more research is needed to confirm this hypothesis.

From randomized controlled trials to observational studies.

PubMed

Silverman, Stuart L

2009-02-01

Randomized controlled trials are considered the gold standard in the hierarchy of research designs for evaluating the efficacy and safety of a treatment intervention. However, their results can have limited applicability to patients in clinical settings. Observational studies using large health care databases can complement findings from randomized controlled trials by assessing treatment effectiveness in patients encountered in day-to-day clinical practice. Results from these designs can expand upon outcomes of randomized controlled trials because of the use of larger and more diverse patient populations with common comorbidities and longer follow-up periods. Furthermore, well-designed observational studies can identify clinically important differences among therapeutic options and provide data on long-term drug effectiveness and safety.

The handsearching of 2 medical journals of Bahrain for reports of randomized controlled trials.

PubMed

Al-Hajeri, Amani A; Fedorowicz, Zbigniew; Amin, Fawzi A; Eisinga, Anne

2006-04-01

To identify reports of randomized trials by handsearching 2 Bahrain medical journals, which are indexed in the biomedical database EMBASE and to determine any added value of the handsearching by comparing the reports found by handsearching with what would have been found by searching EMBASE to examine (i) the precision and sensitivity of the EMBASE index term Randomized Controlled Trial (RCT) and (ii) The Cochrane Collaboration's systematic electronic search of EMBASE (which uses 4 index terms and 9 free-text terms). All issues of the Bahrain Medical Bulletin (BMB) (1979-2004) and the Journal of the Bahrain Medical Society (JBMS) (1989-2004) were handsearched in February 2005 for reports of RCTs or Controlled Clinical Trials (CCTs), according to Cochrane eligibility criteria. Out of 395 articles in BMB we found reports of 12 RCTs and 4 CCTs. Distribution by country of corresponding author: Jordan (4 RCTs, one CCT), Bahrain (one RCT, one CCT), India (3 RCTs, one CCT), Kuwait (one CCT), Saudi Arabia (2 RCTs), USA/Bahrain (one RCT), and Oman (one RCT); and by specialty: Anesthesia (8), Surgery (1) Pediatrics (1), Radiotherapy (1), Community Medicine (1), Sports Medicine (1), Obstetrics/Gynecology (3). The Journal of the Bahrain Medical Society included reports of 14 RCTs and 3 CCTs, out of 97 articles. Distribution by country of corresponding author: Jordan (9 RCTs, 2 CCTs), Bahrain (3 RCTs), Egypt (one RCT), Kuwait (one RCT), and Saudi Arabia (one RCT); and by specialty: Anesthesia (7), General Surgery (3), Obstetrics/Gynecology (1), Radiotherapy (1), Pediatrics (1), Orthopaedic Surgery (1), Education (1) Ear Nose and Throat (1) Ophthalmology (1). Overall, of the 33 reports of trials found by handsearching both journals, only 23 were included in EMBASE of which only 6 had been indexed with the term RCT. Of the 23 reports of trials included in EMBASE, 16 had been identified in the Collaboration s systematic search of EMBASE. Two reports of trials could have been retrieved by this search but there was insufficient information in the title and abstract to code these as trials. The EMBASE records for the remaining 5 reports of trials did not contain terms currently used by The Cochrane Collaboration to identify reports of randomized trials in this database. The handsearching of these journals will help minimize publication bias by locating randomized trials not previously identified and, through their inclusion in the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, will ensure reports of randomized trials will not remain buried through indexing bias.

The importance of preservation of the ethical principle of equipoise in the design of clinical trials: relative impact of the methodological quality domains on the treatment effect in randomized controlled trials.

PubMed

Djulbegovic, Benjamin; Cantor, Alan; Clarke, Mike

2003-01-01

Previous research has identified methodological problems in the design and conduct of randomized trials that could, if left unaddressed, lead to biased results. In this report we discuss one such problem, inadequate control intervention, and argue that it can be by far the most important design characteristic of randomized trials in overestimating the effect of new treatments. Current guidelines for the design and reporting of randomized trials, such as the Consolidated Standards of Reporting Trials (CONSORT) statement, do not address the choice of the comparator intervention. We argue that an adequate control intervention can be selected if people designing a trial explicitly take into consideration the ethical principle of equipoise, also known as "the uncertainty principle."

Antitumor Effects of Somatostatin Analogs in Neuroendocrine Tumors

PubMed Central

Dubé, Pierre; Rinke, Anja

2012-01-01

Background. For decades, somatostatin analogs (including octreotide and lanreotide) have been indicated for relief of the symptoms of flushing, diarrhea, and wheezing associated with secretory neuroendocrine tumors (NETs). Recently, it has been suggested that somatostatin analogs may provide direct and indirect antitumor effects in secretory and nonsecretory NETs in addition to symptom control in secretory NETs. Methods. A systematic review of MEDLINE was conducted to identify studies that investigated the antitumor effects of octreotide or lanreotide for patients with NETs. Additional studies not published in the peer-reviewed literature were identified by searching online abstracts. Results. In all, 17 octreotide trials and 11 lanreotide trials that included antitumor effects were identified. Partial response rates were between 0% and 31%, and stable disease rates were between 15% and 89%. Octreotide was the only somatostatin analog for which results of a phase III, randomized, placebo-controlled clinical trial that investigated antitumor effects were published. After 6 months of treatment in this randomized phase III trial, stable disease was observed in 67% of patients (hazard ratio for time to disease progression: 0.34; 95% confidence interval: 0.20–0.59; p = .000072). Conclusions. In addition to symptom control for NETs, the data support an antitumor effect of somatostatin analogs and suggest that they may slow tumor growth. Long-acting repeatable octreotide has been shown to have an antitumor effect in a randomized phase III trial in midgut NETs, whereas results are pending in a corresponding controlled trial with lanreotide for patients with intestinal and pancreatic primary NETs. PMID:22628056

A qualitative systematic review of head-to-head randomized controlled trials of oral analgesics in neuropathic pain

PubMed Central

Watson, C Peter N; Gilron, Ian; Sawynok, Jana

2010-01-01

BACKGROUND: Neuropathic pain (NP) encompasses many difficult-to-treat disorders. There are few head-to-head, comparative, randomized controlled trials (RCTs) of drugs for NP in different analgesic categories, or of different drugs within a category, despite many placebo-controlled RCTs for individual agents. Well-designed head-to-head comparative trials are an effective way to determine the relative efficacy and safety of a new drug. OBJECTIVE: To perform a systematic review of head-to-head RCTs of oral analgesics in NP. METHODS: A systematic review of RCTs involving NP patients was performed, of which head-to-head comparative trials were selected. Reference lists from published systematic reviews were searched. These studies were rated according to the Jadad scale for quality. RESULTS AND CONCLUSIONS: Twenty-seven such trials were identified. Seventeen were comparisons of different analgesics, and 10 were of different drugs within an analgesic class. Important information was obtained about the relative efficacy and safety of drugs in different categories and within a category. Some significant differences between active treatments were reported. Trial inadequacies were identified. More and improved head-to-head RCTs are needed to inform clinical choices. PMID:20577657

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.

Interconception care for women with a history of gestational diabetes for improving maternal and infant outcomes.

PubMed

Tieu, Joanna; Shepherd, Emily; Middleton, Philippa; Crowther, Caroline A

2017-08-24

Gestational diabetes mellitus (GDM) is associated with adverse health outcomes for mothers and their infants both perinatally and long term. Women with a history of GDM are at risk of recurrence in subsequent pregnancies and may benefit from intervention in the interconception period to improve maternal and infant health outcomes. To assess the effects of interconception care for women with a history of GDM on maternal and infant health outcomes. We searched Cochrane Pregnancy and Childbirth's Trials Register (7 April 2017) and reference lists of retrieved studies. Randomised controlled trials, including quasi-randomised controlled trials and cluster-randomised trials evaluating any protocol of interconception care with standard care or other forms of interconception care for women with a history of GDM on maternal and infant health outcomes. Two review authors independently assessed study eligibility. In future updates of this review, at least two review authors will extract data and assess the risk of bias of included studies; the quality of the evidence will be assessed using the GRADE approach. No eligible published trials were identified. We identified a completed randomised controlled trial that was designed to evaluate the effects of a diet and exercise intervention compared with standard care in women with a history of GDM, however to date, it has only published results on women who were pregnant at randomisation (and not women in the interconception period). We also identified an ongoing trial, in obese women with a history of GDM planning a subsequent pregnancy, which is assessing the effects of an intensive lifestyle intervention, supported with liraglutide treatment, compared with usual care. We also identified a trial that was designed to evaluate the effects of a weight loss and exercise intervention compared with lifestyle education also in obese women with a history of GDM planning a subsequent pregnancy, however it has not yet been published. These trials will be re-considered for inclusion in the next review update. The role of interconception care for women with a history of GDM remains unclear. Randomised controlled trials are required evaluating different forms and protocols of interconception care for these women on perinatal and long-term maternal and infant health outcomes, acceptability of such interventions and cost-effectiveness.

Garlic intake lowers fasting blood glucose: meta-analysis of randomized controlled trials.

PubMed

Hou, Li-qiong; Liu, Yun-hui; Zhang, Yi-yi

2015-01-01

Garlic is a common spicy flavouring agent also used for certain therapeutic purposes. Garlic's effects on blood glucose have been the subject of many clinical and animal studies, however, studies reporting hypoglycemic effects of garlic in humans are conflicting. A comprehensive literature search was conducted to identify relevant trials of garlic or garlic extracts on markers of glycemic control [fasting blood glucose (FBG), postprandial glucose (PPG), glycosylated haemoglobin (HbA1c)]. A meta-analysis of the effect of garlic intake on human was done to assess garlic's effectiveness in lowering glucose levels. Two reviewers extracted data from each of the identified studies. Seven eligible randomized controlled trials with 513 subjects were identified. Pooled analyses showed that garlic intake results in a statistically significant lowering in FBG [SMD=-1.67; 95% CI (-2.80, -0.55), p=0.004]. Our pooled analyses did not include PPG control and HbA1c outcomes. Because only 1 study included in the meta-analysis reported PPG variables and only 2 studies reported HbA1c variables. In conclusion, the current meta-analysis showed that the administration of garlic resulted in a significant reduction in FBG concentrations. More trials are needed to investigate the effectiveness of garlic on HbA1c and PPG.

A systematic review of measurement of endoscopic disease activity and mucosal healing in Crohn's disease: recommendations for clinical trial design.

PubMed

Khanna, Reena; Bouguen, Guillaume; Feagan, Brian G; DʼHaens, Geert; Sandborn, William J; Dubcenco, Elena; Baker, K Adam; Levesque, Barrett G

2014-10-01

Crohn's disease (CD) is a chronic idiopathic inflammatory disorder of the gastrointestinal tract. Recently, mucosal healing has been proposed as a goal of therapy because clinical symptoms are subjective. Evaluative indices that measure endoscopic disease activity are required to define mucosal healing for clinical trials. The primary objective of this systematic review was to assess the existing evaluative indices that measure disease activity in CD and evaluate their role as outcome measures in clinical trials. A systematic literature review was performed using MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and DDW abstracts to identify randomized controlled trials and controlled clinical trials that used a relevant evaluative index from inception to February 2013. The data obtained from these trials were reviewed and summarized. The initial literature searches identified 2300 citations. After duplicates were removed, 1454 studies remained. After application of the apriori inclusion and exclusion criteria, 109 articles were included and 3 were identified with handsearches. In total, 9 evaluative indices for CD were identified and reviewed. The Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score in Crohn's Disease (SES-CD) are indices with the most extensively described operating properties. Both the endoscopic evaluative instrument selected and the definition chosen for mucosal healing affect the validity of assessing endoscopic disease activity during a clinical trial for CD. Currently, the CDEIS and SES-CD have the most data regarding operating properties; however, further validation is required.

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

The Health Informatics Trial Enhancement Project (HITE): Using routinely collected primary care data to identify potential participants for a depression trial

PubMed Central

2010-01-01

Background Recruitment to clinical trials can be challenging. We identified anonymous potential participants to an existing pragmatic randomised controlled depression trial to assess the feasibility of using routinely collected data to identify potential trial participants. We discuss the strengths and limitations of this approach, assess its potential value, report challenges and ethical issues encountered. Methods Swansea University's Health Information Research Unit's Secure Anonymised Information Linkage (SAIL) database of routinely collected health records was interrogated, using Structured Query Language (SQL). Read codes were used to create an algorithm of inclusion/exclusion criteria with which to identify suitable anonymous participants. Two independent clinicians rated the eligibility of the potential participants' identified. Inter-rater reliability was assessed using the kappa statistic and inter-class correlation. Results The study population (N = 37263) comprised all adults registered at five general practices in Swansea UK. Using the algorithm 867 anonymous potential participants were identified. The sensitivity and specificity results > 0.9 suggested a high degree of accuracy from the algorithm. The inter-rater reliability results indicated strong agreement between the confirming raters. The Intra Class Correlation Coefficient (Cronbach's Alpha) > 0.9, suggested excellent agreement and Kappa coefficient > 0.8; almost perfect agreement. Conclusions This proof of concept study showed that routinely collected primary care data can be used to identify potential participants for a pragmatic randomised controlled trial of folate augmentation of antidepressant therapy for the treatment of depression. Further work will be needed to assess generalisability to other conditions and settings and the inclusion of this approach to support Electronic Enhanced Recruitment (EER). PMID:20398303

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.

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.

Sample size and number of outcome measures of veterinary randomised controlled trials of pharmaceutical interventions funded by different sources, a cross-sectional study.

PubMed

Wareham, K J; Hyde, R M; Grindlay, D; Brennan, M L; Dean, R S

2017-10-04

Randomised controlled trials (RCTs) are a key component of the veterinary evidence base. Sample sizes and defined outcome measures are crucial components of RCTs. To describe the sample size and number of outcome measures of veterinary RCTs either funded by the pharmaceutical industry or not, published in 2011. A structured search of PubMed identified RCTs examining the efficacy of pharmaceutical interventions. Number of outcome measures, number of animals enrolled per trial, whether a primary outcome was identified, and the presence of a sample size calculation were extracted from the RCTs. The source of funding was identified for each trial and groups compared on the above parameters. Literature searches returned 972 papers; 86 papers comprising 126 individual trials were analysed. The median number of outcomes per trial was 5.0; there were no significant differences across funding groups (p = 0.133). The median number of animals enrolled per trial was 30.0; this was similar across funding groups (p = 0.302). A primary outcome was identified in 40.5% of trials and was significantly more likely to be stated in trials funded by a pharmaceutical company. A very low percentage of trials reported a sample size calculation (14.3%). Failure to report primary outcomes, justify sample sizes and the reporting of multiple outcome measures was a common feature in all of the clinical trials examined in this study. It is possible some of these factors may be affected by the source of funding of the studies, but the influence of funding needs to be explored with a larger number of trials. Some veterinary RCTs provide a weak evidence base and targeted strategies are required to improve the quality of veterinary RCTs to ensure there is reliable evidence on which to base clinical decisions.

Recruiting Participants for Randomized Controlled Trials

ERIC Educational Resources Information Center

Gallagher, H. Alix; Roschelle, Jeremy; Feng, Mingyu

2014-01-01

The objective of this study was to look across strategies used in a wide range of studies to build a framework for researchers to use in conceptualizing the recruitment process. This paper harvests lessons learned across 19 randomized controlled trials in K-12 school settings conducted by a leading research organization to identify strategies that…

Group Cognitive Behavioural Therapy and Group Recreational Activity for Adults with Autism Spectrum Disorders: A Preliminary Randomized Controlled Trial

ERIC Educational Resources Information Center

Hesselmark, Eva; Plenty, Stephanie; Bejerot, Susanne

2014-01-01

Although adults with autism spectrum disorder are an increasingly identified patient population, few treatment options are available. This "preliminary" randomized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range: cognitive…

Influencing Antecedents of Adolescent Risk-Taking Behaviour in Elementary School: Results of a 4-Year Quasi-Experimental Controlled Trial

ERIC Educational Resources Information Center

Maruska, K.; Morgenstern, M.; Isensee, B.; Hanewinkel, R.

2010-01-01

Effects of the life skills programme "Eigenstandig werden" (Becoming independent) on life skills and on identified antecedents of adolescent health risk behaviour, childhood internalizing and externalizing behaviour were tested in an elementary school setting. A quasi-experimental controlled trial with five repeated measures was…

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.

Characteristics of Placebo Responders in Pediatric Clinical Trials of Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Newcorn, Jeffrey H.; Sutton, Virginia K.; Zhang, Shuyu; Wilens, Timothy; Kratochvil, Christopher; Emslie, Graham J.; D'Souza, Deborah N.; Schuh, Leslie M.; Allen, Albert J.

2009-01-01

Objective: Understanding placebo response is a prerequisite to improving clinical trial methodology. Data from placebo-controlled trials of atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) were analyzed to identify demographic and clinical characteristics that might predict placebo…

Health effects of intermittent fasting: hormesis or harm? A systematic review.

PubMed

Horne, Benjamin D; Muhlestein, Joseph B; Anderson, Jeffrey L

2015-08-01

Intermittent fasting, alternate-day fasting, and other forms of periodic caloric desistance are gaining popularity in the lay press and among animal research scientists. Whether clinical evidence exists for or is strong enough to support the use of such dietary regimens as health interventions is unclear. This review sought to identify rigorous, clinically relevant research studies that provide high-quality evidence that therapeutic fasting regimens are clinically beneficial to humans. A systematic review of the published literature through January 2015 was performed by using sensitive search strategies to identify randomized controlled clinical trials that evaluated the effects of fasting on either clinically relevant surrogate outcomes (e.g., weight, cholesterol) or actual clinical event endpoints [e.g., diabetes, coronary artery disease (CAD)] and any other studies that evaluated the effects of fasting on clinical event outcomes. Three randomized controlled clinical trials of fasting in humans were identified, and the results were published in 5 articles, all of which evaluated the effects of fasting on surrogate outcomes. Improvements in weight and other risk-related outcomes were found in the 3 trials. Two observational clinical outcomes studies in humans were found in which fasting was associated with a lower prevalence of CAD or diabetes diagnosis. No randomized controlled trials of fasting for clinical outcomes were identified. Clinical research studies of fasting with robust designs and high levels of clinical evidence are sparse in the literature. Whereas the few randomized controlled trials and observational clinical outcomes studies support the existence of a health benefit from fasting, substantial further research in humans is needed before the use of fasting as a health intervention can be recommended. © 2015 American Society for Nutrition.

Important issues in the justification of a control treatment in paediatric drug trials.

PubMed

Kelly, Lauren E; Davies, Elin Haf; Saint-Raymond, Agnes; Tomasi, Paolo; Offringa, Martin

2016-10-01

The value of comparative effectiveness trials in informing clinical and policy decisions depends heavily on the choice of control arm (comparator). Our objective is to identify challenges in comparator reasoning and to determine justification criteria for selecting a control arm in paediatric clinical trials. A literature search was completed to identify existing sources of guidance on comparator selection. Subsequently, we reviewed a randomly selected sample of comparators selected for paediatric investigation plans (PIPs) adopted by the Paediatric Committee of the European Medicines Agency in 2013. We gathered descriptive information and evaluated their review process to identify challenges and compromises between regulators and sponsors with regard to the selection of the comparator. A tool to help investigators justify the selection of active controls and placebo arms was developed using the existing literature and empirical data. Justifying comparator selection was a challenge in 28% of PIPs. The following challenging paediatric issues in the decision-making process were identified: use of off-label medications as comparators, ethical and safe use of placebo, duration of placebo use, an undefined optimal dosing strategy, lack of age-appropriate safety and efficacy data, and drug dosing not supported by extrapolation of safety/efficacy evidence from other populations. In order to generate trials that will inform clinical decision-making and support marketing authorisations, researchers must systemically and transparently justify their selection of the comparator arm for their study. This report highlights key areas for justification in the choice of comparator in paediatric clinical trials. 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/

Interventions for increasing fruit and vegetable consumption in children aged 5 years and under

PubMed Central

Wolfenden, Luke; Wyse, Rebecca J; Britton, Ben I; Campbell, Karen J; Hodder, Rebecca K; Stacey, Fiona G; McElduff, Patrick; James, Erica L

2014-01-01

Background Insufficient consumption of fruits and vegetables in childhood increases the risk of future chronic diseases including cardiovascular disease. Objectives To assess the effectiveness, cost-effectiveness and associated adverse events of interventions designed to increase the consumption of fruit and/or vegetables amongst children aged five years and under. Search methods The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 2, 2010, MEDLINE (1950 to 2010 April week 4), EMBASE (1947 to 2010 week 18), CINAHL (up to 12 May 2010), PsycINFO (up to 12 May 2010) and Proquest Dissertations and Theses (up to February 2011) were searched to identify eligible trials, as well as electronic trial registers (also up to February 2011). The reference lists of included trials were reviewed and handsearches of three international nutrition journals were also performed. Authors of all included trials were contacted in order to identify further potentially relevant trials. Selection criteria We included randomised controlled trials (RCTs), including cluster-randomised controlled trials, of any intervention primarily targeting fruit and/or vegetable consumption among children aged five years and under and incorporating a biochemical or dietary assessment of fruit and/or vegetable consumption. Two review authors independently screened the titles and abstracts of identified papers. A third review author with expertise in review methodology resolved any disagreements regarding study eligibility. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias of the included studies. A third reviewer resolved disagreements between review authors. Fixed-effect models were used to perform meta-analysis for the primary review outcomes where a sufficient number of trials with suitable data and homogeneity were identified. Main results Five trials, with 13 trial arms and 3967 participants were included in the review. Two trials examined the impact of specific feeding practices (e.g. repeated food exposure) in increasing child intake of a target vegetable. Two trials assessed the effectiveness of home visiting programs implemented in disadvantaged communities and one trial investigated the effect of a preschool-based intervention in increasing child fruit and vegetable intake. Risk of bias of included studies was low although three of the five trials were judged to be at high risk of performance bias. Meta-analysis of two trials examining repeated food exposure versus a no intervention comparison found no significant difference in target vegetable consumption in the short term (mean difference (MD) 1.37, 95% confidence interval (CI) −2.78 to 5.52). Coupling repeated food exposure with a tangible non-food or social reward, was effective in increasing targeted vegetable consumption in the short term based on one trial. Home visiting programs provided to disadvantaged groups did not significantly increase overall fruit intake in the short term (standardised mean difference (SMD) 0.01, 95% CI −0.09 to 0.11). Similarly, a multi-component preschool-based intervention failed to significantly increase child consumption of vegetables, but did report a small significant increase in mean child consumption of fruit, six months following baseline assessment. None of the trials investigated intervention cost-effectiveness or reported information regarding any adverse events or unintended adverse consequences of the intervention. Authors’ conclusions Despite the importance of encouraging fruit and vegetable consumption among children aged five years and under, this review identified few randomised controlled trials investigating interventions to achieve this. PMID:23152262

Disappointment and adherence among parents of newborns allocated to the control group: a qualitative study of a randomized clinical trial.

PubMed

Meinich Petersen, Sandra; Zoffmann, Vibeke; Kjærgaard, Jesper; Graff Stensballe, Lone; Graff Steensballe, Lone; Greisen, Gorm

2014-04-15

When a child participates in a clinical trial, informed consent has to be given by the parents. Parental motives for participation are complex, but the hope of getting a new and better treatment for the child is important. We wondered how parents react when their child is allocated to the control group of a randomized controlled trial, and how it will affect their future engagement in the trial. We included parents of newborns randomized to the control arm in the Danish Calmette study at Rigshospitalet in Copenhagen. The Calmette study is a randomized clinical trial investigating the non-specific effects of early BCG-vaccine to healthy neonates. Randomization is performed immediately after birth and parents are not blinded to the allocation. We set up a semi-structured focus group with six parents from four families. Afterwards we telephone-interviewed another 19 mothers to achieve saturation. Thematic analysis was used to identify themes across the data sets. The parents reported good understanding of the randomization process. Their most common reaction to allocation was disappointment, though relief was also seen. A model of reactions to being allocated to the control group was developed based on the participants' different positions along two continuities from 'Our participation in trial is not important' to 'Our participation in trial is important', and 'Vaccine not important to us' to 'Vaccine important to us'. Four very disappointed families had thought of getting the vaccine elsewhere, and one had actually had their child vaccinated. All parents involved in the focus group and the telephone interviews wanted to participate in the follow-ups planned for the Calmette study. This study identified an almost universal experience of disappointment among parents of newborns who were randomized to the control group, but also a broad expression of understanding and accepting the idea of randomization. The trial staff might use the model of reactions in understanding the parents' disappointment and in this way support their motives for participation. A generalized version might be applicable across randomized controlled trials at large. The Calmette study is registered in EudraCT (https://eudract.ema.europa.eu/) with trial number 2010-021979-85.

Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion.

PubMed

Hill, S R; Carless, P A; Henry, D A; Carson, J L; Hebert, P C; McClelland, D B; Henderson, K M

2002-01-01

Most clinical practice guidelines recommend restrictive red cell transfusion practices with the goal of minimising exposure to allogeneic blood (from an unrelated donor). The purpose of this review is to compare clinical outcomes in patients randomised to restrictive versus liberal transfusion thresholds (triggers). To examine the evidence on the effect of transfusion thresholds, on the use of allogeneic and/or autologous blood, and the evidence for any effect on clinical outcomes. Trials were identified by: computer searches of OVID Medline (1966 to December 2000), Current Contents (1993 to Week 48 2000), and the Cochrane Controlled Trials Register (2000 Issue 4). References in identified trials and review articles were checked and authors contacted to identify any additional studies. Controlled trials in which patients were randomised to an intervention group or to a control group. Trials were included where the intervention groups were assigned on the basis of a clear transfusion "trigger", described as a haemoglobin (Hb) or haematocrit (Hct) level below which a RBC transfusion was to be administered. Trial quality was assessed using criteria proposed by Schulz et al. (1995). Relative risks of requiring allogeneic blood transfusion, transfused blood volumes and other clinical outcomes were pooled across trials using a random effects model. Ten trials were identified that reported outcomes for a total of 1780 patients. Restrictive transfusion strategies reduced the risk of receiving a red blood cell (RBC) transfusion by a relative 42% (RR=0.58: 95%CI=0.47,0.71). This equates to an average absolute risk reduction (ARR) of 40% (95%CI=24% to 56%). The volume of RBCs transfused was reduced on average by 0.93 units (95%CI=0.36,1.5 units). However, heterogeneity between these trials was statistically significant (p<0.00001) for these outcomes. Mortality, rates of cardiac events, morbidity, and length of hospital stay were unaffected. Trials were of poor methodological quality. The limited published evidence supports the use of restrictive transfusion triggers in patients who are free of serious cardiac disease. However, most of the data on clinical outcomes were generated by a single trial. The effects of conservative transfusion triggers on functional status, morbidity and mortality, particularly in patients with cardiac disease, need to be tested in further large clinical trials. In countries with inadequate screening of donor blood the data may constitute a stronger basis for avoiding transfusion with allogeneic red cells.

Using the 'Social Marketing Mix Framework' to explore recruitment barriers and facilitators in palliative care randomised controlled trials? A narrative synthesis review.

PubMed

Dunleavy, Lesley; Walshe, Catherine; Oriani, Anna; Preston, Nancy

2018-05-01

Effective recruitment to randomised controlled trials is critically important for a robust, trustworthy evidence base in palliative care. Many trials fail to achieve recruitment targets, but the reasons for this are poorly understood. Understanding barriers and facilitators is a critical step in designing optimal recruitment strategies. To identify, explore and synthesise knowledge about recruitment barriers and facilitators in palliative care trials using the '6 Ps' of the 'Social Marketing Mix Framework'. A systematic review with narrative synthesis. Medline, CINAHL, PsycINFO and Embase databases (from January 1990 to early October 2016) were searched. Papers included the following: interventional and qualitative studies addressing recruitment, palliative care randomised controlled trial papers or reports containing narrative observations about the barriers, facilitators or strategies to increase recruitment. A total of 48 papers met the inclusion criteria. Uninterested participants (Product), burden of illness (Price) and 'identifying eligible participants' were barriers. Careful messaging and the use of scripts/role play (Promotion) were recommended. The need for intensive resources and gatekeeping by professionals were barriers while having research staff on-site and lead clinician support (Working with Partners) was advocated. Most evidence is based on researchers' own reports of experiences of recruiting to trials rather than independent evaluation. The 'Social Marketing Mix Framework' can help guide researchers when planning and implementing their recruitment strategy but suggested strategies need to be tested within embedded clinical trials. The findings of this review are applicable to all palliative care research and not just randomised controlled trials.

Recruiting participants with peripheral arterial disease for clinical trials: experience from the Study to Improve Leg Circulation (SILC).

PubMed

McDermott, Mary M; Domanchuk, Kathryn; Dyer, Alan; Ades, Philip; Kibbe, Melina; Criqui, Michael H

2009-03-01

To describe the success of diverse recruitment methods in a randomized controlled clinical trial of exercise in persons with peripheral arterial disease (PAD). An analysis of recruitment sources conducted for the 746 men and women completing a baseline visit for the study to improve leg circulation (SILC), a randomized controlled trial of exercise for patients with PAD. For each recruitment source, we determined the number of randomized participants, the rate of randomization among those completing a baseline visit, and cost per randomized participant. Of the 746 individuals who completed a baseline visit, 156 were eligible and randomized. The most frequent sources of randomized participants were newspaper advertising (n = 67), mailed recruitment letters to patients with PAD identified at the study medical center (n = 25), and radio advertising (n = 18). Costs per randomized participant were $2750 for television advertising, $2167 for Life Line Screening, $2369 for newspaper advertising, $3931 for mailed postcards to older community dwelling men and women, and $5691 for radio advertising. Among those completing a baseline visit, randomization rates ranged from 10% for those identified from radio advertising to 32% for those identified from the Chicago Veterans Administration and 33% for those identified from posted flyers. Most participants in a randomized controlled trial of exercise were recruited from newspaper advertising and mailed recruitment letters to patients with known PAD. The highest randomization rates after a baseline visit occurred among participants identified from posted flyers and mailed recruitment letters to PAD patients.

Effectiveness of a Web-Based Intervention to Reduce Alcohol Consumption among French Hazardous Drinkers: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Guillemont, Juliette; Cogordan, Chloé; Nalpas, Bertrand; Nguyen-Thanh, Vi?t; Richard, Jean-Baptiste; Arwidson, Pierre

2017-01-01

This study aims to evaluate the effectiveness of a web-based intervention to reduce alcohol consumption among hazardous drinkers. A two-group parallel randomized controlled trial was conducted among adults identified as hazardous drinkers according to the Alcohol Use Disorders Identification Test. The intervention delivers personalized normative…

Attachment-Based Family Therapy for Adolescents with Suicidal Ideation: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Diamond, Guy S.; Wintersteen, Matthew B.; Brown, Gregory K.; Diamond, Gary M.; Gallop, Robert; Shelef, Karni; Levy, Suzanne

2010-01-01

Objective: To evaluate whether Attachment-Based Family Therapy (ABFT) is more effective than Enhanced Usual Care (EUC) for reducing suicidal ideation and depressive symptoms in adolescents. Method: This was a randomized controlled trial of suicidal adolescents between the ages of 12 and 17, identified in primary care and emergency departments. Of…

Poor reporting of scientific leadership information in clinical trial registers.

PubMed

Sekeres, Melanie; Gold, Jennifer L; Chan, An-Wen; Lexchin, Joel; Moher, David; Van Laethem, Marleen L P; Maskalyk, James; Ferris, Lorraine; Taback, Nathan; Rochon, Paula A

2008-02-20

In September 2004, the International Committee of Medical Journal Editors (ICMJE) issued a Statement requiring that all clinical trials be registered at inception in a public register in order to be considered for publication. The World Health Organization (WHO) and ICMJE have identified 20 items that should be provided before a trial is considered registered, including contact information. Identifying those scientifically responsible for trial conduct increases accountability. The objective is to examine the proportion of registered clinical trials providing valid scientific leadership information. We reviewed clinical trial entries listing Canadian investigators in the two largest international and public trial registers, the International Standard Randomized Controlled Trial Number (ISRCTN) register, and ClinicalTrials.gov. The main outcome measures were the proportion of clinical trials reporting valid contact information for the trials' Principal Investigator (PI)/Co-ordinating Investigator/Study Chair/Site PI, and trial e-mail contact address, stratified by funding source, recruiting status, and register. A total of 1388 entries (142 from ISRCTN and 1246 from ClinicalTrials.gov) comprised our sample. We found non-compliance with mandatory registration requirements regarding scientific leadership and trial contact information. Non-industry and partial industry funded trials were significantly more likely to identify the individual responsible for scientific leadership (OR = 259, 95% CI: 95-701) and to provide a contact e-mail address (OR = 9.6, 95% CI: 6.6-14) than were solely industry funded trials. Despite the requirements set by WHO and ICMJE, data on scientific leadership and contact e-mail addresses are frequently omitted from clinical trials registered in the two leading public clinical trial registers. To promote accountability and transparency in clinical trials research, public clinical trials registers should ensure adequate monitoring of trial registration to ensure completion of mandatory contact information fields identifying scientific leadership.

Antibacterial agents in composite restorations for the prevention of dental caries.

PubMed

Pereira-Cenci, Tatiana; Cenci, Maximiliano S; Fedorowicz, Zbys; Azevedo, Marina

2013-12-17

Dental caries is a multifactorial disease in which the fermentation of food sugars by bacteria from the biofilm (dental plaque) leads to localised demineralisation of tooth surfaces, which may ultimately result in cavity formation. Resin composites are widely used in dentistry to restore teeth. These restorations can fail for a number of reasons, such as secondary caries, and restorative material fracture and other minor reasons. From these, secondary caries, which are caries lesions developed adjacent to restorations, is the main cause for restorations replacement. The presence of antibacterials in both the filling material and the bonding systems would theoretically be able to affect the initiation and progression of caries adjacent to restorations. This is an update of the Cochrane review published in 2009. To assess the effects of antibacterial agents incorporated into composite restorations for the prevention of dental caries. We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 23 July 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 6), MEDLINE via OVID (1946 to 23 July 2013) and EMBASE via OVID (1980 to 23 July 2013). We searched the US National Institutes of Health Trials Register (http://clinicaltrials.gov), the metaRegister of Controlled Trials (www.controlled-trials.com) and the World Health Organization International Clinical Trials Registry platform (www.who.int/trialsearch) for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Randomised controlled trials comparing resin composite restorations containing antibacterial agents with composite restorations not containing antibacterial agents. Two review authors conducted screening of studies in duplicate and independently, and although no eligible trials were identified, the two authors had planned to extract data independently and assess trial quality using standard Cochrane Collaboration methodologies. We retrieved 308 references to studies, none of which matched the inclusion criteria for this review and all of which were excluded. We were unable to identify any randomised controlled trials on the effects of antibacterial agents incorporated into composite restorations for the prevention of dental caries. The absence of high level evidence for the effectiveness of this intervention emphasises the need for well designed, adequately powered, randomised controlled clinical trials. Thus, conclusions remain the same as the previously published review, with no included clinical trials.

A systematic review of models to predict recruitment to multicentre clinical trials.

PubMed

Barnard, Katharine D; Dent, Louise; Cook, Andrew

2010-07-06

Less than one third of publicly funded trials managed to recruit according to their original plan often resulting in request for additional funding and/or time extensions. The aim was to identify models which might be useful to a major public funder of randomised controlled trials when estimating likely time requirements for recruiting trial participants. The requirements of a useful model were identified as usability, based on experience, able to reflect time trends, accounting for centre recruitment and contribution to a commissioning decision. A systematic review of English language articles using MEDLINE and EMBASE. Search terms included: randomised controlled trial, patient, accrual, predict, enroll, models, statistical; Bayes Theorem; Decision Theory; Monte Carlo Method and Poisson. Only studies discussing prediction of recruitment to trials using a modelling approach were included. Information was extracted from articles by one author, and checked by a second, using a pre-defined form. Out of 326 identified abstracts, only 8 met all the inclusion criteria. Of these 8 studies examined, there are five major classes of model discussed: the unconditional model, the conditional model, the Poisson model, Bayesian models and Monte Carlo simulation of Markov models. None of these meet all the pre-identified needs of the funder. To meet the needs of a number of research programmes, a new model is required as a matter of importance. Any model chosen should be validated against both retrospective and prospective data, to ensure the predictions it gives are superior to those currently used.

A systematic review of randomized controlled trials using music therapy for children.

PubMed

Mrázová, Marcela; Celec, Peter

2010-10-01

Music therapy is a promising approach widening the potential applications of psychotherapy. Music influences both, psychologic and physiologic parameters, and children are especially responsive to this form of therapy. Many aspects of its action mechanisms remain to be elucidated, underscoring the need for evidence-based medicine (EBM) for clinical use of music therapy. This review seeks to highlight some of the issues of music therapy research and to initiate a discussion about the need for international multicenter cooperation to bring scientifically sound evidence of the benefits of music therapy in pediatric patients. Scientific bibliographic databases were searched for randomized controlled trials on use of music therapy for children. Identified articles were evaluated according to criteria for scientific quality. Twenty-eight studies were identified. Most of the trials were biased by the number of participants, and some trials showed the need to improve design of control groups. Indeed, the novelty of this area of study has produced a large number of different studies (with variability in diagnoses, interventions, control groups, duration, and/or outcome parameters), and there is a need for a more homogeneous and systematic approach. Available studies highlight the need to address reproducibility issues. This analysis identifies the need for a subsequent series of clinical studies on the efficacy of music in the pediatric population, with more focus on eligibility criteria with respect to EBM and reproducibility.

Identifying additional studies for a systematic review of retention strategies in randomised controlled trials: making contact with trials units and trial methodologists.

PubMed

Brueton, Valerie; Tierney, Jayne F; Stenning, Sally; Rait, Greta

2017-08-22

Search strategies for systematic reviews aim to identify all evidence relevant to the research question posed. Reports of methodological research can be difficult to find leading to biased results in systematic reviews of research methodology. Evidence suggests that contact with investigators can help to identify unpublished research. To identify additional eligible randomised controlled trials (RCTs) for a Cochrane systematic review of strategies to improve retention in RCTs, we conducted a survey of UK clinical trials units (CTUs) and made contact with RCT methodologists. Key contacts for all UK CTUs were sent a personalised email with a short questionnaire and summary protocol of the Cochrane methodology review. The questionnaire asked whether a RCT evaluating strategies to improve retention embedded in a RCT had ever been conducted by the CTU. Questions about the stage of completion and publication of such RCTs were included. The summary protocol outlined the aims, eligibility criteria, examples of types of retention strategies, and the primary outcome for the systematic review. Personal communication with RCT methodologists and presentations of preliminary results of the review at conferences were also used to identify additional eligible RCTs. We checked the results of our standard searches to see if eligible studies identified through these additional methods were also found using our standard searches. We identified 14 of the 38 RCTs included in the Cochrane methodology review by contacting trials units and methodologists. Eleven of the 14 RCTs identified by these methods were either published in grey literature, in press or unpublished. Three remaining RCTs were fully published at the time. Six of the RCTs identified were not found through any other searches. The RCTs identified represented data for 6 of 14 RCTs of incentive strategies (52% of randomised participants included in the review), and 6 of 14 RCTs of communication strategies (52% of randomised participants included in the Cochrane review). Data were unavailable for two of the RCTs identified. Methodological evaluations embedded in RCTs may be unpublished, published in the grey literature or where published, poorly indexed in bibliographic databases. To identify such studies and minimise selection bias in systematic reviews of methodological evaluations, reviewers should consider contacting CTUs and trial methodologists.

Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials

PubMed Central

Isomura, T; Suzuki, S; Origasa, H; Hosono, A; Suzuki, M; Sawada, T; Terao, S; Muto, Y; Koga, T

2016-01-01

There remain liver-related safety concerns, regarding potential hepatotoxicity in humans, induced by green tea intake, despite being supposedly beneficial. Although many randomized controlled trials (RCTs) of green tea extracts have been reported in the literature, the systematic reviews published to date were only based on subjective assessment of case reports. To more objectively examine the liver-related safety of green tea intake, we conducted a systematic review of published RCTs. A systematic literature search was conducted using three databases (PubMed, EMBASE and Cochrane Central Register of Controlled Trials) in December 2013 to identify RCTs of green tea extracts. Data on liver-related adverse events, including laboratory test abnormalities, were abstracted from the identified articles. Methodological quality of RCTs was assessed. After excluding duplicates, 561 titles and abstracts and 119 full-text articles were screened, and finally 34 trials were identified. Of these, liver-related adverse events were reported in four trials; these adverse events involved seven subjects (eight events) in the green tea intervention group and one subject (one event) in the control group. The summary odds ratio, estimated using a meta-analysis method for sparse event data, for intervention compared with placebo was 2.1 (95% confidence interval: 0.5–9.8). The few events reported in both groups were elevations of liver enzymes. Most were mild, and no serious liver-related adverse events were reported. Results of this review, although not conclusive, suggest that liver-related adverse events after intake of green tea extracts are expected to be rare. PMID:27188915

Desmopressin acetate (DDAVP) for preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.

PubMed

Karanth, Laxminarayan; Barua, Ankur; Kanagasabai, Sachchithanantham; Nair, Sreekumar

2015-09-09

Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of desmopressin acetate in these groups of pregnant women should be evaluated.This is an update of a Cochrane review first published in 2013. To determine the efficacy of desmopressin acetate in preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched for any randomised controlled trials in a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of most recent search: 18 June 2015. Randomised and quasi-randomised controlled trials investigating the efficacy of desmopressin acetate versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. The review did not identify any randomised controlled trials investigating the relative effectiveness of desmopressin acetate for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with desmopressin acetate.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using desmopressin acetate in this population are needed.

Desmopressin acetate (DDAVP) for preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.

PubMed

Karanth, Laxminarayan; Barua, Ankur; Kanagasabai, Sachchithanantham; Nair, N S

2013-04-30

Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of desmopressin acetate in these groups of pregnant women should be evaluated. To determine the efficacy of desmopressin acetate in preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched for any randomised controlled trials in a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of most recent search: 28 February 2013. Randomised and quasi-randomised controlled trials investigating the efficacy of desmopressin acetate versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. The review did not identify any randomised controlled trials investigating the relative effectiveness of desmopressin acetate for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with desmopressin acetate.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using desmopressin acetate in this population are needed.

CONSORT item reporting quality in the top ten ranked journals of critical care medicine in 2011: a retrospective analysis.

PubMed

Stevanovic, Ana; Schmitz, Sabine; Rossaint, Rolf; Schürholz, Tobias; Coburn, Mark

2015-01-01

Reporting randomised controlled trials is a key element in order to disseminate research findings. The CONSORT statement was introduced to improve the reporting quality. We assessed the adherence to the CONSORT statement of randomised controlled trials published 2011 in the top ten ranked journals of critical care medicine (ISI Web of Knowledge 2011, Thomson Reuters, London UK). Design. We performed a retrospective cross sectional data analysis. Setting. This study was executed at the University Hospital of RWTH, Aachen. Participants. We selected the following top ten listed journals according to ISI Web of Knowledge (Thomson Reuters, London, UK) critical care medicine ranking in the year 2011: American Journal of Respiratory and Critical Care Medicine, Critical Care Medicine, Intensive Care Medicine, CHEST, Critical Care, Journal of Neurotrauma, Resuscitation, Pediatric Critical Care Medicine, Shock and Minerva Anestesiologica. Main outcome measures. We screened the online table of contents of each included journal, to identify the randomised controlled trials. The adherence to the items of the CONSORT Checklist in each trial was evaluated. Additionally we correlated the citation frequency of the articles and the impact factor of the respective journal with the amount of reported items per trial. We analysed 119 randomised controlled trials and found, 15 years after the implementation of the CONSORT statement, that a median of 61,1% of the checklist-items were reported. Only 55.5% of the articles were identified as randomised trials in their titles. The citation frequency of the trials correlated significantly (rs = 0,433; p<0,001 and r = 0,331; p<0,001) to the CONSORT statement adherence. The impact factor showed also a significant correlation to the CONSORT adherence (r = 0,386; p<0,001). The reporting quality of randomised controlled trials in the field of critical care medicine remains poor and needs considerable improvement.

Medial tibial stress syndrome: evidence-based prevention.

PubMed

Craig, Debbie I

2008-01-01

Thacker SB, Gilchrist J, Stroup DF, Kimsey CD. The prevention of shin splints in sports: a systematic review of literature. Med Sci Sports Exerc. 2002;34(1):32-40. Among physically active individuals, which medial tibial stress syndrome (MTSS) prevention methods are most effective to decrease injury rates? Studies were identified by searching MEDLINE (1966-2000), Current Contents (1996-2000), Biomedical Collection (1993-1999), and Dissertation Abstracts. Reference lists of identified studies were searched manually until no further studies were identified. Experts in the field were contacted, including first authors of randomized controlled trials addressing prevention of MTSS. The Cochrane Collaboration (early stage of Cochrane Database of Systematic Reviews) was contacted. Inclusion criteria included randomized controlled trials or clinical trials comparing different MTSS prevention methods with control groups. Excluded were studies that did not provide primary research data or that addressed treatment and rehabilitation rather than prevention of incident MTSS. A total of 199 citations were identified. Of these, 4 studies compared prevention methods for MTSS. Three reviewers independently scored the 4 studies. Reviewers were blinded to the authors' names and affiliations but not the results. Each study was evaluated independently for methodologic quality using a 100-point checklist. Final scores were averages of the 3 reviewers' scores. Prevention methods studied were shock-absorbent insoles, foam heel pads, Achilles tendon stretching, footwear, and graduated running programs. No statistically significant results were noted for any of the prevention methods. Median quality scores ranged from 29 to 47, revealing flaws in design, control for bias, and statistical methods. No current evidence supports any single prevention method for MTSS. The most promising outcomes support the use of shock-absorbing insoles. Well-designed and controlled trials are critically needed to decrease the incidence of this common injury.

Residents-as-teachers programs in psychiatry: a systematic review.

PubMed

Dewey, Charlene M; Coverdale, John H; Ismail, Nadia J; Culberson, John W; Thompson, Britta M; Patton, Cynthia S; Friedland, Joan A

2008-02-01

Because psychiatry residents have important roles as teachers and significant opportunities to contribute to medical student education, we set out to: identify all randomized control trials (RCT) for residents' teaching skills programs in psychiatry and to identify the efficacy of those interventions for improving teaching skills; identify the strengths and weaknesses of the available studies across medical disciplines; and identify currently available methods for enhancing residents' teaching skills for residents training in psychiatry. The published English-language literature was searched using PubMed, Social Sciences Index, and PsycINFO databases, with key search words including: residents, teaching skills, residents as teachers, psychiatry, and assessments. Both RCT and controlled, nonrandomized trials of residents' teaching programs directed to enhance residents' teaching skills were selected and critically appraised. Of 13 trials identified and reviewed, most included residents in internal medicine. Only one included psychiatry residents and assessed their ability to teach interviewing skills to medical students. Along with other studies, this study demonstrated improvement in residents' teaching skills. Overall, interventions and outcome measures were heterogeneous while the quality of methodologies varied. Five studies were of higher quality, representing examples of quality educational research. Several described group differences, blinding, good follow-up, and use of valid, reliable tools. Only one trial exists that incorporated psychiatry residents. Significant opportunity to advance educational research in this field exists. Psychiatry residency program directors should incorporate high-quality methodologies and can benefit from the findings of trials in other disciplines.

Effectiveness of Exercise Interventions to Improve Postural Control in Older Adults: A Systematic Review and Meta-Analyses of Centre of Pressure Measurements.

PubMed

Low, Daniel C; Walsh, Gregory S; Arkesteijn, Marco

2017-01-01

Previous reviews have shown balance in older adults to be improved with exercise. However, it is currently unclear whether postural control, indicated by centre of pressure (COP) measurement, can be improved in older adults and thus whether postural control could be a mechanism to improve balance. The purpose of this systematic review was to assess the effectiveness of force platform COP variables to identify changes in postural control following exercise interventions in older adults. In addition, a secondary purpose was to determine whether the exercise types (balance, resistance or multi-component exercise interventions) are equally effective to improve postural control. Randomised controlled trials were identified using searches of databases and reference lists (PROSPERO registration number CRD42014010617). Trials performing exercise interventions, reporting force platform COP measurements, in participants with a mean age of ≥60 years were included. Risk of bias assessments were performed following the Cochrane guidelines. Data were pooled in meta-analyses, and standardised mean differences (SMDs) with 95 % confidence intervals (CIs) were calculated. Twenty-three trials met the inclusion criteria for the systematic review. Twenty-two trials could be defined as either utilising a balance, resistance or multi-component exercise intervention. These 22 trials were used in the meta-analyses. All trials reported measurements of double leg stance; eight trials reported additional stance conditions. The meta-analyses of double leg stance showed that balance exercise interventions significantly decreased total sway path length/velocity [SMD -1.13, 95 % CI -1.75 to -0.51 (eyes open); SMD -0.79, 95 % CI -1.33 to -0.26 (eyes closed)] and anterior-posterior sway path length/velocity [SMD -1.02, 95 % CI -2.01 to -0.02 (eyes open); SMD -0.82, 95 % CI -1.46 to -0.17 (eyes closed)] in both eyes open and eyes closed conditions. Balance exercise interventions also decreased sway area in eyes closed conditions (SMD -0.57, 95 % CI -1.01 to -0.13) and medio-lateral sway path length/velocity in eyes open conditions (SMD -0.8, 95 % CI -1.48 to -0.12). In contrast, neither resistance nor multi-component exercise interventions affected any of the included COP measurements. Postural control is improved by balance exercise interventions. In contrast, strength or multi-component exercise interventions did not influence postural control measurements in older adults. In addition, a lack of standardisation in collection protocol and COP variables calculated across trials was identified.

Association between bibliometric parameters, reporting and methodological quality of randomised controlled trials in vascular and endovascular surgery.

PubMed

Hajibandeh, Shahab; Hajibandeh, Shahin; Antoniou, George A; Green, Patrick A; Maden, Michelle; Torella, Francesco

2017-04-01

Purpose We aimed to investigate association between bibliometric parameters, reporting and methodological quality of vascular and endovascular surgery randomised controlled trials. Methods The most recent 75 and oldest 75 randomised controlled trials published in leading journals over a 10-year period were identified. The reporting quality was analysed using the CONSORT statement, and methodological quality with the Intercollegiate Guidelines Network checklist. We used exploratory univariate and multivariable linear regression analysis to investigate associations. Findings Bibliometric parameters such as type of journal, study design reported in title, number of pages; external funding, industry sponsoring and number of citations are associated with reporting quality. Moreover, parameters such as type of journal, subject area and study design reported in title are associated with methodological quality. Conclusions The bibliometric parameters of randomised controlled trials may be independent predictors for their reporting and methodological quality. Moreover, the reporting quality of randomised controlled trials is associated with their methodological quality and vice versa.

Protecting patient privacy when sharing patient-level data from clinical trials.

PubMed

Tucker, Katherine; Branson, Janice; Dilleen, Maria; Hollis, Sally; Loughlin, Paul; Nixon, Mark J; Williams, Zoë

2016-07-08

Greater transparency and, in particular, sharing of patient-level data for further scientific research is an increasingly important topic for the pharmaceutical industry and other organisations who sponsor and conduct clinical trials as well as generally in the interests of patients participating in studies. A concern remains, however, over how to appropriately prepare and share clinical trial data with third party researchers, whilst maintaining patient confidentiality. Clinical trial datasets contain very detailed information on each participant. Risk to patient privacy can be mitigated by data reduction techniques. However, retention of data utility is important in order to allow meaningful scientific research. In addition, for clinical trial data, an excessive application of such techniques may pose a public health risk if misleading results are produced. After considering existing guidance, this article makes recommendations with the aim of promoting an approach that balances data utility and privacy risk and is applicable across clinical trial data holders. Our key recommendations are as follows: 1. Data anonymisation/de-identification: Data holders are responsible for generating de-identified datasets which are intended to offer increased protection for patient privacy through masking or generalisation of direct and some indirect identifiers. 2. Controlled access to data, including use of a data sharing agreement: A legally binding data sharing agreement should be in place, including agreements not to download or further share data and not to attempt to seek to identify patients. Appropriate levels of security should be used for transferring data or providing access; one solution is use of a secure 'locked box' system which provides additional safeguards. This article provides recommendations on best practices to de-identify/anonymise clinical trial data for sharing with third-party researchers, as well as controlled access to data and data sharing agreements. The recommendations are applicable to all clinical trial data holders. Further work will be needed to identify and evaluate competing possibilities as regulations, attitudes to risk and technologies evolve.

Do open label blinded outcome studies of novel anticoagulants versus warfarin have equivalent validity to those carried out under double-blind conditions?

PubMed

O'Neil, William M; Welner, Sharon A; Lip, Gregory Y H

2013-03-01

Recent anticoagulants for stroke prevention in AF have been tested in active comparator controlled studies versus warfarin using two designs: double-blind, double-dummy and prospective randomised, open blinded endpoint (PROBE). The former requires elaborate procedures to maintain blinding, while PROBE does not. Outcomes of double-blind and PROBE designed studies of novel anticoagulants for AF, focusing on warfarin controls, were explored. Major, Phase III warfarin-controlled trials for stroke prevention in AF were identified. Odds ratios (ORs) of key outcomes for active comparators versus VKA and event rates for VKA arms were compared between designs, in context of baseline demographics and inclusion criteria. Identified trials studied five novel anticoagulants in three each of PROBE and double-blind design. For ORs of results across studies and outcomes, there was little pattern differentiating the two designs. Among VKA-control subjects, event rates for the primary outcome (stroke or systemic embolism) in PROBE trials at 1.74 %/year (95% confidence interval: 1.54-1.95) was not significantly different from that in double-blind trials, at 1.88 (1.73-2.03). Among other outcomes, VKA-treated subjects in both trial designs had similar event rates, apart from higher all-cause mortality in ROCKET AF, and lower myocardial infarction rates among the PROBE study patients. Although there are differences in outcome between PROBE and double blind trials, they do not appear to be design-related. The exacting requirements of double-blinding in AF trials may not be necessary.

Benefits and Harms of Sick Leave: Lack of Randomized, Controlled Trials

ERIC Educational Resources Information Center

Axelsson, Inge; Marnetoft, Sven-Uno

2010-01-01

The aim of this study was to try to identify those randomized controlled trials that compare sick leave with no sick leave or a different duration or degree of sick leave. A comprehensive, systematic, electronic search of Clinical Evidence, the Cochrane Library and PubMed, and a manual search of the Campbell Library and a journal supplement was…

Interventions for preventing or treating alcohol hangover: systematic review of randomised controlled trials

PubMed Central

Pittler, Max H; Verster, Joris C; Ernst, Edzard

2005-01-01

Objective To assess the clinical evidence on the effectiveness of any medical intervention for preventing or treating alcohol hangover. Data sources Systematic searches on Medline, Embase, Amed, Cochrane Central, the National Research Register (UK), and ClincalTrials.gov (USA); hand searches of conference proceedings and bibliographies; contact with experts and manufacturers of commercial preparations. Language of publication was not restricted. Study selection and data extraction All randomised controlled trials of any medical intervention for preventing or treating alcohol hangover were included. Trials were considered if they were placebo controlled or controlled against a comparator intervention. Titles and abstracts of identified articles were read and hard copies were obtained. The selection of studies, data extraction, and validation were done independently by two reviewers. The Jadad score was used to evaluate methodological quality. Results Fifteen potentially relevant trials were identified. Seven publications failed to meet all inclusion criteria. Eight randomised controlled trials assessing eight different interventions were reviewed. The agents tested were propranolol, tropisetron, tolfenamic acid, fructose or glucose, and the dietary supplements Borago officinalis (borage), Cynara scolymus (artichoke), Opuntia ficus-indica (prickly pear), and a yeast based preparation. All studies were double blind. Significant intergroup differences for overall symptom scores and individual symptoms were reported only for tolfenamic acid, γ linolenic acid from B officinalis, and a yeast based preparation. Conclusion No compelling evidence exists to suggest that any conventional or complementary intervention is effective for preventing or treating alcohol hangover. The most effective way to avoid the symptoms of alcohol induced hangover is to practise abstinence or moderation. PMID:16373736

Effectiveness of treatments for infantile colic: systematic review.

PubMed

Lucassen, P L; Assendelft, W J; Gubbels, J W; van Eijk, J T; van Geldrop, W J; Neven, A K

1998-05-23

To evaluate the effectiveness of diets, drug treatment, and behavioural interventions on infantile colic in trials with crying or the presence of colic as the primary outcome measure. Controlled clinical trials identified by a highly sensitive search strategy in Medline (1966-96), Embase (1986-95), and the Cochrane Controlled Trials Register, in combination with reference checking for further relevant publications. Keywords were crying and colic. Two independent assessors selected controlled trials with interventions lasting at least 3 days that included infants younger than 6 months who cried excessively. Methodological quality was assessed by two assessors independently with a quality assessment scale (range 0-5). Effect sizes were calculated as percentage success. Effect sizes of trials using identical interventions were pooled using a random effects model. 27 controlled trials were identified. Elimination of cows' milk protein was effective when substituted by hypoallergenic formula milks (effect size 0.22 (95% confidence interval 0.09 to 0.34)). The effectiveness of substitution by soy formula milks was unclear when only trials of good methodological quality were considered. The benefit of eliminating cows' milk protein was not restricted to highly selected populations. Dicyclomine was effective (effect size 0.46 (0.33 to 0.60)), but serious side effects have been reported. The advice to reduce stimulation was beneficial (effect size 0.48 (0.23 to 0.74)), whereas the advice to increase carrying and holding seemed not to reduce crying. No benefit was shown for simethicone. Uncertainty remained about the effectiveness of low lactose formula milks. Infantile colic should preferably be treated by advising carers to reduce stimulation and with a one week trial of a hypoallergenic formula milk.

Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications.

PubMed

Kasenda, Benjamin; Schandelmaier, Stefan; Sun, Xin; von Elm, Erik; You, John; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J; Stegert, Mihaela; Olu, Kelechi K; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M; Mertz, Dominik; Akl, Elie A; Bassler, Dirk; Busse, Jason W; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Rosenthal, Rachel; Ebrahim, Shanil; Vandvik, Per O; Johnston, Bradley C; Walter, Martin A; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G; Bucher, Heiner C; Guyatt, Gordon H; Briel, Matthias

2014-07-16

To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. Cohort of protocols of randomised controlled trial and subsequent full journal publications. Six research ethics committees in Switzerland, Germany, and Canada. 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials. © The DISCO study group 2014.

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.

A systematic review of randomised controlled trials assessing effectiveness of prosthetic and orthotic interventions

PubMed Central

Farmer, Sybil; Pandyan, Anand; Chockalingam, Nachiappan

2018-01-01

Background Assistive products are items which allow older people and people with disabilities to be able to live a healthy, productive and dignified life. It has been estimated that approximately 1.5% of the world’s population need a prosthesis or orthosis. Objective The objective of this study was to systematically identify and review the evidence from randomized controlled trials assessing effectiveness and cost-effectiveness of prosthetic and orthotic interventions. Methods Literature searches, completed in September 2015, were carried out in fourteen databases between years 1995 and 2015. The search results were independently screened by two reviewers. For the purpose of this manuscript, only randomized controlled trials which examined interventions using orthotic or prosthetic devices were selected for data extraction and synthesis. Results A total of 342 randomised controlled trials were identified (319 English language and 23 non-English language). Only 4 of these randomised controlled trials examined prosthetic interventions and the rest examined orthotic interventions. These orthotic interventions were categorised based on the medical conditions/injuries of the participants. From these studies, this review focused on the medical condition/injuries with the highest number of randomised controlled trials (osteoarthritis, fracture, stroke, carpal tunnel syndrome, plantar fasciitis, anterior cruciate ligament, diabetic foot, rheumatoid and juvenile idiopathic arthritis, ankle sprain, cerebral palsy, lateral epicondylitis and low back pain). The included articles were assessed for risk of bias using the Cochrane Risk of Bias tool. Details of the clinical population examined, the type of orthotic/prosthetic intervention, the comparator/s and the outcome measures were extracted. Effect sizes and odds ratios were calculated for all outcome measures, where possible. Conclusions At present, for prosthetic and orthotic interventions, the scientific literature does not provide sufficient high quality research to allow strong conclusions on their effectiveness and cost-effectiveness. PMID:29538382

A pilot effectiveness study of the Enhancing Parenting Skills (EPaS) 2014 programme for parents of children with behaviour problems: study protocol for a randomised controlled trial.

PubMed

Williams, Margiad Elen; Hutchings, Judy

2015-05-20

The Enhancing Parenting Skills (EPaS) 2014 programme is a home-based, health visitor-delivered parenting support programme for parents of children with identified behaviour problems. This trial aims to evaluate the effectiveness of the EPaS 2014 programme compared to a waiting-list treatment as usual control group. This is a pragmatic, multicentre randomised controlled trial. Sixty health visitors will each be asked to identify two families that have a child scoring above the clinical cut-off for behaviour problems using the Eyberg Child Behaviour Inventory (ECBI). Families recruited to the trial will be randomised in a 1:1 ratio into an intervention or waiting-list control group. Randomisation will occur within health visitor to ensure that each health visitor has one intervention family and one control family. The primary outcome is change in child behaviour problems as measured by the parent-reported ECBI. Secondary outcomes include other measures of child behaviour, parent behaviour, and parental depression as measured by parent-reports and an independent observation of parent and child behaviour. Follow-up measures will be collected 6-months after the collection of baseline measures. This is the first rigorous evaluation of the EPaS 2014 programme. The trial will provide important information on the effectiveness of a one-to-one home-based intervention, delivered by health visitors, for pre-school children with behaviour problems. It will also examine potential mediating (improved parent behaviour and/or improved parental depression) and moderating (single parent, teenage parent, poverty, low education level) factors. Current Controlled Trials ISRCTN06867279 (18 June 2014).

Using Discrete Trial Training to Identify Specific Learning Impairments in Boys with Fragile X Syndrome

ERIC Educational Resources Information Center

Hall, Scott S.; Hustyi, Kristin M.; Hammond, Jennifer L.; Hirt, Melissa; Reiss, Allan L.

2014-01-01

We examined whether "discrete trial training" (DTT) could be used to identify learning impairments in mathematical reasoning in boys with fragile X syndrome (FXS). Boys with FXS, aged 10-23 years, and age and IQ-matched controls, were trained to match fractions to pie-charts and pie-charts to decimals either on a computer or with a…

Glycerin laxatives for prevention or treatment of feeding intolerance in very low birth weight infants.

PubMed

Anabrees, Jasim; Shah, Vibhuti S; AlOsaimi, Ahlam; AlFaleh, Khalid

2015-09-30

Feeding intolerance is a common clinical problem among preterm infants. It may be an early sign of necrotising enterocolitis, sepsis or other serious gastrointestinal conditions, or it may result from gut immaturity with delayed passage of meconium. Glycerin laxatives stimulate passage of meconium by acting as an osmotic dehydrating agent and increasing osmotic pressure in the gut; they stimulate rectal contraction, potentially reducing the incidence of feeding intolerance. To assess the effectiveness and safety of glycerin laxatives (enemas/suppositories) for prevention or treatment of feeding intolerance in very low birth weight (VLBW) infants. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 4), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We restricted our search to all randomised controlled trials and applied no language restrictions. We searched the references of identified studies and reviews on this topic and handsearched for additional articles. We searched the database maintained by the US National Institutes of Health (www.clinicaltrials.gov) and European trial registries to identify ongoing trials. We considered only randomised or quasi-randomised controlled trials that enrolled preterm infants < 32 weeks' gestational age (GA) and/or < 1500 g birth weight. We included trials if they administered glycerin laxatives and measured at least one prespecified clinical outcome. We used standard methods of The Cochrane Collaboration and its Neonatal Group to assess methodological quality of trials, to collect data and to perform analyses. We identified three trials that evaluated use of prophylactic glycerin laxatives in preterm infants. We identified no trials that evaluated therapeutic use of glycerin laxatives for feeding intolerance. Our review showed that prophylactic administration of glycerin laxatives did not reduce the time required to achieve full enteral feeds and did not influence secondary outcomes, including duration of hospital stay, mortality and weight at discharge. Prophylactic administration of glycerin laxatives resulted in failure of fewer infants to pass stool over the first 48 hours. Included trials reported no adverse events. Our review of available evidence for glycerin laxatives does not support the routine use of prophylactic glycerin laxatives in clinical practice. Additional studies are needed to confirm or refute the effectiveness and safety of glycerin laxatives for prevention or treatment of feeding intolerance in VLBW infants.

Yoga for Adults with Type 2 Diabetes: A Systematic Review of Controlled Trials

PubMed Central

Innes, Kim E.; Selfe, Terry Kit

2016-01-01

A growing body of evidence suggests yogic practices may benefit adults with type 2 diabetes (DM2). In this systematic review, we evaluate available evidence from prospective controlled trials regarding the effects of yoga-based programs on specific health outcomes pertinent to DM2 management. To identify qualifying studies, we searched nine databases and scanned bibliographies of relevant review papers and all identified articles. Controlled trials that did not target adults with diabetes, included only adults with type 1 diabetes, were under two-week duration, or did not include quantitative outcome data were excluded. Study quality was evaluated using the PEDro scale. Thirty-three papers reporting findings from 25 controlled trials (13 nonrandomized, 12 randomized) met our inclusion criteria (N = 2170 participants). Collectively, findings suggest that yogic practices may promote significant improvements in several indices of importance in DM2 management, including glycemic control, lipid levels, and body composition. More limited data suggest that yoga may also lower oxidative stress and blood pressure; enhance pulmonary and autonomic function, mood, sleep, and quality of life; and reduce medication use in adults with DM2. However, given the methodological limitations of existing studies, additional high-quality investigations are required to confirm and further elucidate the potential benefits of yoga programs in populations with DM2. PMID:26788520

Randomized controlled trials in pediatric complementary and alternative medicine: Where can they be found?

PubMed Central

Sampson, Margaret; Campbell, Kaitryn; Ajiferuke, Isola; Moher, David

2003-01-01

Background The safety and effectiveness of CAM interventions are of great relevance to pediatric health care providers. The objective of this study is to identify sources of reported randomized controlled trials (RCTs) in the field of pediatric complementary and alternative medicine (CAM). Methods Reports of RCTs were identified by searching Medline and 12 additional bibliographic databases and by reviewing the reference lists of previously identified pediatric CAM systematic reviews. Results We identified 908 reports of RCTs that included children under 18 and investigated a CAM therapy. Since 1965, there has been a steady growth in the number of these trials that are being published. The four journals that published the most reported RCTs are The American Journal of Clinical Nutrition, Pediatrics, Journal of Pediatrics, and Lancet. Medline, CAB Health, and Embase were the best database sources for identifying these studies; they indexed 93.2%, 58.4% and 42.2 % respectively of the journals publishing reports of pediatric CAM RCTs. Conclusions Those working or interested in the field of pediatric CAM should routinely search Medline, CAB Health and Embase for literature in the field. The four core journals identified above should be included in their collection. PMID:12589711

Describing qualitative research undertaken with randomised controlled trials in grant proposals: a documentary analysis.

PubMed

Drabble, Sarah J; O'Cathain, Alicia; Thomas, Kate J; Rudolph, Anne; Hewison, Jenny

2014-02-18

There is growing recognition of the value of conducting qualitative research with trials in health research. It is timely to reflect on how this qualitative research is presented in grant proposals to identify lessons for researchers and research commissioners. As part of a larger study focusing on how to maximise the value of undertaking qualitative research with trials, we undertook a documentary analysis of proposals of funded studies. Using the metaRegister of Controlled Trials (mRCT) database we identified trials funded in the United Kingdom, ongoing between 2001 and 2010, and reporting the use of qualitative research. We requested copies of proposals from lead researchers. We extracted data from the proposals using closed and open questions, analysed using descriptive statistics and content analysis respectively. 2% (89/3812) of trials in the mRCT database described the use of qualitative research undertaken with the trial. From these 89 trials, we received copies of 36 full proposals, of which 32 met our inclusion criteria. 25% used less than a single paragraph to describe the qualitative research. The aims of the qualitative research described in these proposals focused mainly on the intervention or trial conduct. Just over half (56%) of the proposals included an explicit rationale for conducting the qualitative research with the trial, the most frequent being to optimise implementation into clinical practice or to interpret trial findings. Key information about methods, expertise and resources was missing in a large minority of proposals, in particular sample size, type of analysis, and non-personnel resources. 28% specifically stated that qualitative researchers would conduct the qualitative research. Our review of proposals of successfully funded studies identified good practice but also identified limited space given to describing the qualitative research, with an associated lack of attention to the rationale for doing the qualitative research and important methodological details. Acknowledging the space restrictions faced by researchers writing grant proposals, we suggest a starting point for providing practical guidance to help researchers write proposals and research commissioners assess proposals of qualitative research with trials.

Describing qualitative research undertaken with randomised controlled trials in grant proposals: a documentary analysis

PubMed Central

2014-01-01

Background There is growing recognition of the value of conducting qualitative research with trials in health research. It is timely to reflect on how this qualitative research is presented in grant proposals to identify lessons for researchers and research commissioners. As part of a larger study focusing on how to maximise the value of undertaking qualitative research with trials, we undertook a documentary analysis of proposals of funded studies. Methods Using the metaRegister of Controlled Trials (mRCT) database we identified trials funded in the United Kingdom, ongoing between 2001 and 2010, and reporting the use of qualitative research. We requested copies of proposals from lead researchers. We extracted data from the proposals using closed and open questions, analysed using descriptive statistics and content analysis respectively. Results 2% (89/3812) of trials in the mRCT database described the use of qualitative research undertaken with the trial. From these 89 trials, we received copies of 36 full proposals, of which 32 met our inclusion criteria. 25% used less than a single paragraph to describe the qualitative research. The aims of the qualitative research described in these proposals focused mainly on the intervention or trial conduct. Just over half (56%) of the proposals included an explicit rationale for conducting the qualitative research with the trial, the most frequent being to optimise implementation into clinical practice or to interpret trial findings. Key information about methods, expertise and resources was missing in a large minority of proposals, in particular sample size, type of analysis, and non-personnel resources. 28% specifically stated that qualitative researchers would conduct the qualitative research. Conclusions Our review of proposals of successfully funded studies identified good practice but also identified limited space given to describing the qualitative research, with an associated lack of attention to the rationale for doing the qualitative research and important methodological details. Acknowledging the space restrictions faced by researchers writing grant proposals, we suggest a starting point for providing practical guidance to help researchers write proposals and research commissioners assess proposals of qualitative research with trials. PMID:24533771

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.

A systematic review of evidence for the effectiveness of practitioner-based complementary and alternative therapies in the management of rheumatic diseases: osteoarthritis.

PubMed

Macfarlane, Gary J; Paudyal, Priya; Doherty, Michael; Ernst, Edzard; Lewith, George; MacPherson, Hugh; Sim, Julius; Jones, Gareth T

2012-12-01

To critically review the evidence on the efficacy and effectiveness of practitioner-based complementary therapies for patients with osteoarthritis. We excluded t'ai chi and acupuncture, which have been the subject of recent reviews. Randomized controlled trials, published in English up to May 2011, were identified using systematic searches of bibliographic databases and searching of reference lists. Information was extracted on outcomes, statistical significance in comparison with alternative treatments and reported side effects. The methodological quality of the identified studies was determined using the Jadad scoring system. Outcomes considered were pain and patient global assessment. In all, 16 eligible trials were identified covering 12 therapies. Overall, there was no good evidence of the effectiveness of any of the therapies in relation to pain or global health improvement/quality of life because most therapies only had a single randomized controlled trial. Where positive results were reported, they were often comparing an active intervention with no intervention. Therapies with multiple trials either provided null (biofeedback) or inconsistent results (magnet therapy), or the trials available scored poorly for quality (chiropractic). There were few adverse events reported in the trials. There is not sufficient evidence to recommend any of the practitioner-based complementary therapies considered here for the management of OA, but neither is there sufficient evidence to conclude that they are not effective or efficacious.

Practices that minimize trauma to the genital tract in childbirth: a systematic review of the literature.

PubMed

Renfrew, M J; Hannah, W; Albers, L; Floyd, E

1998-09-01

Trauma to the genital tract commonly occurs at birth, and can cause short- and long-term morbidity. Clinical measures to reduce its occurrence have not been fully identified. A systematic review of the English language literature was conducted to describe the current state of knowledge on reduction of genital tract trauma before planning a large randomized controlled trial of ways to prevent such trauma. Randomized trials and other published reports were identified from relevant databases and hand searches. Studies were reviewed and assessed using a structured format. A total of 77 papers and chapters were identified and placed into 5 categories after critical review: 25 randomized trials, 4 meta-analyses, 4 prospective studies, 36 retrospective studies, and 8 descriptions of practice from textbooks. The available evidence is conclusive in favor of restricted use of episiotomy. The contribution of maternal characteristics and attitudes to intact perineum has not been investigated. Several other topics warrant further study, including maternal position, style of pushing, and antenatal perineal massage. Strong opinions and sparse data exist regarding the role of hand maneuvers by the birth attendant for perineal management and birth of the baby. This became the topic of the planned randomized controlled trial, which was completed; results will be published soon. The case for restricting the use of episiotomy is conclusive. Several other clinical factors warrant investigation, including the role of hand maneuvers by the birth attendant in preventing birth trauma. A large randomized controlled trial will report on this topic.

Effective behaviour change techniques in the prevention and management of childhood obesity.

PubMed

Martin, J; Chater, A; Lorencatto, F

2013-10-01

Rates of childhood obesity are increasing, and it is essential to identify the active components of interventions aiming to prevent and manage obesity in children. A systematic review of behaviour change interventions was conducted to find evidence of behaviour change techniques (BCTs) that are most effective in changing physical activity and/or eating behaviour for the prevention or management of childhood obesity. An electronic search was conducted for randomised controlled trials published between January 1990 and December 2009. Of 4309 titles and abstracts screened, full texts of 135 articles were assessed, of which 17 published articles were included in this review. Intervention descriptions were coded according to the behaviour-specific CALO-RE taxonomy of BCTs. BCTs were identified and compared across obesity management (n=9) vs prevention (n=8) trials. To assess the effectiveness of individual BCTs, trials were further divided into those that were effective (defined as either a group reduction of at least 0.13 body mass index (BMI) units or a significant difference in BMI between intervention and control groups at follow-up) vs non-effective (reported no significant differences between groups). We reliably identified BCTs utilised in effective and non-effective prevention and management trials. To illustrate the relative effectiveness of each BCT, effectiveness ratios were calculated as the ratio of the number of times each BCT was a component of an intervention in an effective trial divided by the number of times they were a component of all trials. Results indicated six BCTs that may be effective components of future management interventions (provide information on the consequences of behaviour to the individual, environmental restructuring, prompt practice, prompt identification as role model/position advocate, stress management/emotional control training and general communication skills training), and one that may be effective in prevention interventions (prompting generalisation of a target behaviour). We identified that for management trials, providing information on the consequences of behaviour in general was a feature of non-effective interventions and for prevention trials, providing information on the consequences of behaviour in general, providing rewards contingent on successful behaviour and facilitating social comparison were non-effective. To design effective behaviour change programmes for the prevention and management of childhood obesity, we would recommend utilising the BCTs identified as effective in this review. The impact on intervention effectiveness of combining BCTs should be the topic of further research.

Methodological reporting quality of randomized controlled trials: A survey of seven core journals of orthopaedics from Mainland China over 5 years following the CONSORT statement.

PubMed

Zhang, J; Chen, X; Zhu, Q; Cui, J; Cao, L; Su, J

2016-11-01

In recent years, the number of randomized controlled trials (RCTs) in the field of orthopaedics is increasing in Mainland China. However, randomized controlled trials (RCTs) are inclined to bias if they lack methodological quality. Therefore, we performed a survey of RCT to assess: (1) What about the quality of RCTs in the field of orthopedics in Mainland China? (2) Whether there is difference between the core journals of the Chinese department of orthopedics and Orthopaedics Traumatology Surgery & Research (OTSR). This research aimed to evaluate the methodological reporting quality according to the CONSORT statement of randomized controlled trials (RCTs) in seven key orthopaedic journals published in Mainland China over 5 years from 2010 to 2014. All of the articles were hand researched on Chongqing VIP database between 2010 and 2014. Studies were considered eligible if the words "random", "randomly", "randomization", "randomized" were employed to describe the allocation way. Trials including animals, cadavers, trials published as abstracts and case report, trials dealing with subgroups analysis, or trials without the outcomes were excluded. In addition, eight articles selected from Orthopaedics Traumatology Surgery & Research (OTSR) between 2010 and 2014 were included in this study for comparison. The identified RCTs are analyzed using a modified version of the Consolidated Standards of Reporting Trials (CONSORT), including the sample size calculation, allocation sequence generation, allocation concealment, blinding and handling of dropouts. A total of 222 RCTs were identified in seven core orthopaedic journals. No trials reported adequate sample size calculation, 74 (33.4%) reported adequate allocation generation, 8 (3.7%) trials reported adequate allocation concealment, 18 (8.1%) trials reported adequate blinding and 16 (7.2%) trials reported handling of dropouts. In OTSR, 1 (12.5%) trial reported adequate sample size calculation, 4 (50.0%) reported adequate allocation generation, 1 (12.5%) trials reported adequate allocation concealment, 2 (25.0%) trials reported adequate blinding and 5 (62.5%) trials reported handling of dropouts. There were statistical differences as for sample size calculation and handling of dropouts between papers from Mainland China and OTSR (P<0.05). The findings of this study show that the methodological reporting quality of RCTs in seven core orthopaedic journals from the Mainland China is far from satisfaction and it needs to further improve to keep up with the standards of the CONSORT statement. Level III case control. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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.

Interventions for hyperthyroidism pre-pregnancy and during pregnancy.

PubMed

Earl, Rachel; Crowther, Caroline A; Middleton, Philippa

2013-11-19

Women with hyperthyroidism in pregnancy have increased risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and they can develop severe pre-eclampsia or placental abruption. To identify interventions used in the management of hyperthyroidism pre-pregnancy or during pregnancy and to ascertain the impact of these interventions on important maternal, fetal, neonatal and childhood outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2013). We planned to include randomised controlled trials, quasi-randomised controlled trials, and cluster-randomised trials comparing antithyroid interventions for hyperthyroidism pre-pregnancy or during pregnancy with another intervention or no intervention (placebo or no treatment). Two review authors assessed trial eligibility and planned to assess trial quality and extract the data independently. No trials were included in the review. As we did not identify any eligible trials, we are unable to comment on implications for practice, although early identification of hyperthyroidism before pregnancy may allow a woman to choose radioactive iodine therapy or surgery before planning to have a child. Designing and conducting a trial of antithyroid interventions for pregnant women with hyperthyroidism presents formidable challenges. Not only is hyperthyroidism a relatively rare condition, both of the two main drugs used have potential for harm, one for the mother and the other for the child. More observational research is required about the potential harms of methimazole in early pregnancy and about the potential liver damage from propylthiouracil.

The Cognitive Effects of Antidepressants in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

PubMed Central

Rosenblat, Joshua D; Kakar, Ron

2016-01-01

Background: Cognitive dysfunction is often present in major depressive disorder (MDD). Several clinical trials have noted a pro-cognitive effect of antidepressants in MDD. The objective of the current systematic review and meta-analysis was to assess the pooled efficacy of antidepressants on various domains of cognition in MDD. Methods: Trials published prior to April 15, 2015, were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, Embase, PsychINFO, Clinicaltrials.gov, and relevant review articles. Data from randomized clinical trials assessing the cognitive effects of antidepressants were pooled to determine standard mean differences (SMD) using a random-effects model. Results: Nine placebo-controlled randomized trials (2 550 participants) evaluating the cognitive effects of vortioxetine (n = 728), duloxetine (n = 714), paroxetine (n = 23), citalopram (n = 84), phenelzine (n = 28), nortryptiline (n = 32), and sertraline (n = 49) were identified. Antidepressants had a positive effect on psychomotor speed (SMD 0.16; 95% confidence interval [CI] 0.05–0.27; I2 = 46%) and delayed recall (SMD 0.24; 95% CI 0.15–0.34; I2 = 0%). The effect on cognitive control and executive function did not reach statistical significance. Of note, after removal of vortioxetine from the analysis, statistical significance was lost for psychomotor speed. Eight head-to-head randomized trials comparing the effects of selective serotonin reuptake inhibitors (SSRIs; n = 371), selective serotonin and norepinephrine reuptake inhibitors (SNRIs; n = 25), tricyclic antidepressants (TCAs; n = 138), and norepinephrine and dopamine reuptake inhibitors (NDRIs; n = 46) were identified. No statistically significant difference in cognitive effects was found when pooling results from head-to-head trials of SSRIs, SNRIs, TCAs, and NDRIs. Significant limitations were the heterogeneity of results, limited number of studies, and small sample sizes. Conclusions: Available evidence suggests that antidepressants have a significant positive effect on psychomotor speed and delayed recall. PMID:26209859

Assessing treatment-as-usual provided to control groups in adherence trials: Exploring the use of an open-ended questionnaire for identifying behaviour change techniques.

PubMed

Oberjé, Edwin J M; Dima, Alexandra L; Pijnappel, Frank J; Prins, Jan M; de Bruin, Marijn

2015-01-01

Reporting guidelines call for descriptions of control group support in equal detail as for interventions. However, how to assess the active content (behaviour change techniques (BCTs)) of treatment-as-usual (TAU) delivered to control groups in trials remains unclear. The objective of this study is to pre-test a method of assessing TAU in a multicentre cost-effectiveness trial of an HIV-treatment adherence intervention. HIV-nurses (N = 21) completed a semi-structured open-ended questionnaire enquiring about TAU adherence counselling. Two coders independently coded BCTs. Completeness and clarity of nurse responses, inter-coder reliabilities and the type of BCTs reported were examined. The clarity and completeness of nurse responses were adequate. Twenty-three of the 26 identified BCTs could be reliably coded (mean κ = .79; mean agreement rate = 96%) and three BCTs scored below κ = .60. Total number of BCTs reported per nurse ranged between 7 and 19 (M = 13.86, SD = 3.35). This study suggests that the TAU open-ended questionnaire is a feasible and reliable tool to capture active content of support provided to control participants in a multicentre adherence intervention trial. Considerable variability in the number of BCTs provided to control patients was observed, illustrating the importance of reliably collecting and accurately reporting control group support.

A systematic review of models to predict recruitment to multicentre clinical trials

PubMed Central

2010-01-01

Background Less than one third of publicly funded trials managed to recruit according to their original plan often resulting in request for additional funding and/or time extensions. The aim was to identify models which might be useful to a major public funder of randomised controlled trials when estimating likely time requirements for recruiting trial participants. The requirements of a useful model were identified as usability, based on experience, able to reflect time trends, accounting for centre recruitment and contribution to a commissioning decision. Methods A systematic review of English language articles using MEDLINE and EMBASE. Search terms included: randomised controlled trial, patient, accrual, predict, enrol, models, statistical; Bayes Theorem; Decision Theory; Monte Carlo Method and Poisson. Only studies discussing prediction of recruitment to trials using a modelling approach were included. Information was extracted from articles by one author, and checked by a second, using a pre-defined form. Results Out of 326 identified abstracts, only 8 met all the inclusion criteria. Of these 8 studies examined, there are five major classes of model discussed: the unconditional model, the conditional model, the Poisson model, Bayesian models and Monte Carlo simulation of Markov models. None of these meet all the pre-identified needs of the funder. Conclusions To meet the needs of a number of research programmes, a new model is required as a matter of importance. Any model chosen should be validated against both retrospective and prospective data, to ensure the predictions it gives are superior to those currently used. PMID:20604946

High School Students with Reading Comprehension Difficulties: Results of a Randomized Control Trial of a Two-Year Reading Intervention

ERIC Educational Resources Information Center

Vaughn, Sharon; Roberts, Greg; Wexler, Jade; Vaughn, Michael G.; Fall, Anna-Mária; Schnakenberg, Jennifer B.

2015-01-01

A 2-year, randomized control trial with 9th to 10th grade students with significant reading problems was provided for 50 minutes a day in small groups. Comparison students were provided an elective class and treatment students the reading intervention. Students were identified as demonstrating reading difficulties through failure on their state…

Systematic Review and Meta-analysis: Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis

PubMed Central

Zou, Guangyong; Parker, Claire E.; Macdonald, John K.; Mosli, Mahmoud H.; Khanna, Reena; Shackelton, Lisa M.; Vandervoort, Margaret K.; AlAmeel, Turki; Al Beshir, Mohammad; AlMadi, Majid; Al-Taweel, Talal; Atkinson, Nathan S. S.; Biswas, Sujata; Chapman, Thomas P.; Dulai, Parambir S.; Glaire, Mark A.; Hoekman, Daniel; Koutsoumpas, Andreas; Minas, Elizabeth; Samaan, Mark A.; Travis, Simon; D’Haens, Geert; Levesque, Barrett G.; Sandborn, William J.; Feagan, Brian G.

2016-01-01

Background and Aims: Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in ulcerative colitis [UC] clinical trials, and factors influencing this are poorly understood. We quantify placebo response and remission rates in UC RCTs and identify trial design factors influencing them. Methods: MEDLINE, EMBASE, and the Cochrane Library were searched from inception through April 2014 for placebo-controlled trials in adult patients with UC of a biological agent, corticosteroid, immunosuppressant, or aminosalicylate. Data were independently doubly extracted. Quality was assessed using the Cochrane risk of bias tool. Results: In all, 51 trials [48 induction and 10 maintenance phases] were identified. Placebo response and remission rates were pooled according to random-effects models, and mixed-effects meta-regression models were used to evaluate effects of study-level characteristics on these rates. Pooled estimates of placebo remission and response rates for induction trials were 10% (95% confidence interval [CI] 7-13%) and 33% [95% CI 29-37%], respectively. Corresponding values for maintenance trials were 19% [95% CI 11-30%] and 22% [95% CI 17-28%]. Trials enrolling patients with more active disease confirmed by endoscopy [endoscopy subscore ≥ 2] were associated with lower placebo rates. Conversely, placebo rates increased with increasing trial duration and number of study visits. Conclusions: Objective assessment of greater disease activity at trial entry by endoscopy lowered placebo rates, whereas increasing trial duration and more interactions with healthcare providers increased placebo rates. These findings have important implications for design and conduct of clinical trials. PMID:26746169

Effect of Lycopene Supplementation on Oxidative Stress: An Exploratory Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Chen, Jinyao; Song, Yang

2013-01-01

Abstract Lycopene is a potentially useful compound for preventing and treating cardiovascular diseases and cancers. Studies on the effects of lycopene on oxidative stress offer insights into its mechanism of action and provide evidence-based rationale for its supplementation. In this analysis, randomized controlled trials of the effects of oral lycopene supplementation on any valid outcomes of oxidative stress were identified and pooled through a search of international journal databases and reference lists of relevant publications. Two reviewers extracted data from each of the identified studies. Only studies of sufficient quality were included. Twelve parallel trials and one crossover trial were included in the systematic review, and six trials provided data for quantitative meta-analysis. Our results indicate that lycopene supplementation significantly decreases the DNA tail length, as determined using comet assays, with a mean difference (MD) of −6.27 [95% confidence interval (CI) −10.74, −1.90] (P=.006) between the lycopene intervention groups and the control groups. Lycopene supplementation does not significantly prolong the lag time of low-density lipoprotein (MD 3.76 [95% CI −2.48, 10.01]; P=.24). Lycopene possibly alleviates oxidative stress; however, biomarker research for oxidative stress needs be more consistent with the outcomes in lycopene intervention trials for disease prevention. PMID:23631493

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.

Therapeutic effects of antimicrobial treatment during lactation of recently acquired bovine subclinical mastitis: two linked randomized field trials.

PubMed

van den Borne, B H P; van Schaik, G; Lam, T J G M; Nielen, M

2010-01-01

Two linked randomized field trials were performed on 39 herds in the Netherlands to 1) determine therapeutic effects of antimicrobial treatment of recently acquired subclinical mastitis (RASCM) during lactation, 2) evaluate the effect of duration of subclinical mastitis on therapeutic outcome, and 3) identify factors related to the therapeutic success of RASCM. Cows with a first elevated composite somatic cell count (CSCC) after 2 consecutive low CSCC measurements were eligible for enrollment in trial 1 (treatment at the first elevated CSCC). Quarter milk samples were collected to determine bacteriological status for major pathogens and coagulase-negative staphylococci. Cows with one or more culture-positive quarters with a quarter somatic cell count (QSCC) >or=100,000 cells/mL were defined to have RASCM and were randomly assigned treatment or control (no treatment). Untreated cows from trial 1 that had a second elevated CSCC at the next milk recording were eligible for enrollment in trial 2 (treatment at the second elevated CSCC). In trial 2, staphylococci-positive cows (Staphylococcus aureus and coagulase-negative staphylococci) were randomly assigned to treatment or control. Farmers used their own treatment protocols to treat quarters in both trials. Bacteriological cure was defined as absence of the pathogen identified pre-intervention in 2 samples post-intervention; QSCC, CSCC, and milk yield were also analyzed. Hierarchical logistic and linear models were used to determine therapeutic effects and to identify factors related to therapy outcome. Treated quarters had a higher bacteriological cure rate than control quarters for all pathogens in both trials. Treatment resulted in lower QSCC and CSCC, whereas milk yield was not affected by treatment. Bacteriological cure of RASCM was better in quarters with a low QSCC pre-intervention and in coagulase-negative staphylococci-positive quarters. Control quarters with a single culture-positive sample pre-intervention also had a higher bacteriological cure than control quarters with >or=2 culture-positive samples. Time of antimicrobial treatment affected bacteriological cure for penicillin-sensitive Staph. aureus. Bacteriological cure tended to be higher for Staph. aureus after treatment at the first elevated CSCC compared with treatment at the second elevated CSCC. Thus, early treatment of Staph. aureus might be more effective than later treatment. Copyright 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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

Sham Acupressure Controls Used in Randomized Controlled Trials: A Systematic Review and Critique

PubMed Central

Tan, Jing-Yu; Suen, Lorna K. P.; Wang, Tao; Molassiotis, Alexander

2015-01-01

Objectives To explore the commonly utilized sham acupressure procedures in existing acupressure trials, and to assess whether different types of sham interventions yield different therapeutic outcomes, and, as far as possible, to identify directions for the future development of an adequate sham acupressure method. Methods Randomized controlled trials comparing true acupressure with sham interventions were included. Thirteen electronic databases were adopted to locate relevant studies from inception to July 3, 2014. Meanwhile, eight Chinese journals on complementary and alternative medicine were manually searched to locate eligible articles. In addition, eligible studies listed in the reference lists of the included papers and other related systematic reviews on acupressure were also screened to further search any potentially eligible trials. Methodological quality of the included studies was evaluated using the risk of bias assessment tool developed by the Cochrane Back Review Group. Descriptive analysis was adopted to summarize the therapeutic outcomes. Results Sixty-six studies with 7265 participants were included. Methodological quality of the included trials was generally satisfactory. Six types of sham acupressure approaches were identified and “non-acupoint” stimulation was the most frequently utilized sham point while an acupressure device was the most commonly used approach for administering sham treatments. Acupressure therapy was a beneficial approach in managing a variety of health problems and the therapeutic effect was found to be more effective in the true acupressure groups than that in the sham comparative groups. No clear association could be identified between different sham acupressure modalities and the reported treatment outcomes. Conclusions A great diversity of sham acupressure controls have been used in clinical practice and research. A solid conclusion whether different sham alternatives are related to different treatment outcomes cannot be derived because of significant clinical heterogeneity among the analyzed trials. Non-acupoints are generally recommended but the definite locations should be identified with caution. For studies using single sham acupoints on hands or legs, it is suggested to apply identical acupressure devices on the same acupoint as in the active intervention without any stimulation. While for studies on pain, stimulation of sham acupoints should be avoided. PMID:26177378

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.

Patient recruitment for clinical trials on traditional Chinese medicine: Challenges, barriers, and strategies.

PubMed

King-Fai, Cheng; Ping-Chung, Leung; Lai-Yi, Wong; Yuet-Shim, Fong

2008-02-02

Failure to recruit sufficient numbers of participants is a major barrier to the completion of randomized controlled trials in traditional Chinese medicine (TCM) clinical trials. The purpose of this paper is to analyze the commonly used strategies for the recruitment of patients in TCM clinical trials, to identify the most common reasons for attrition and refusal, and to identify barriers and potential solutions to the difficulties. There are four stages in the actual recruitment process, which included introducing the project to the potential patients, explaining how to implement the project, assessing and intensifying the understanding and facilitating patient decision-making. When insufficient recruitment occurred, the following steps should be considered: reevaluating the required sample size; adding new sites to the trial; eliminating hospitals that had poor recruiting records; extending the patient recruitment period, modifying the patient inclusion/exclusion criteria; and shifting placebo-controlled to active-controlled arrangements. Success in reaching target recruitment depended largely on being able to directly contact patients through posters, newspaper advertisements, television interviews, patient support groups, and physician referrals in hospitals. Suspicions against the placebo and unwillingness to stop taking other herbal supplements made recruitment more difficult, time-consuming, and costly. In a Chinese community, open advertising in the local newspaper may be particularly attractive.

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

Magnitude of blood pressure reduction in the placebo arms of modern hypertension trials: implications for trials of renal denervation.

PubMed

Patel, Hitesh C; Hayward, Carl; Ozdemir, Baris Ata; Rosen, Stuart D; Krum, Henry; Lyon, Alexander R; Francis, Darrel P; di Mario, Carlo

2015-02-01

Early phase studies of novel interventions for hypertension, such as renal sympathetic denervation, are sometimes single-armed (uncontrolled). We explored the wisdom of this by quantifying the blood pressure fall in the placebo arms of contemporary trials of hypertension. We searched Medline up to June 2014 and identified blinded, randomized trials of hypertension therapy in which the control arm received placebo medication or a sham (placebo) procedure. For nonresistant hypertension, we have identified all such trials of drugs licensed by the US Food and Drug Administration since 2000 (5 drugs). This US Food and Drug Administration-related restriction was not applied to resistant hypertension trials. This produced 7451 patients, who were allocated to a blinded control from 52 trials of nonresistant hypertension and 694 patients from 8 trials of resistant hypertension (3 drugs and 2 interventions). Systolic blood pressure fell by 5.92 mm Hg (95% confidence interval, 5.14-6.71; P<0.0001) in the nonresistant cohort and by 8.76 mm Hg (95% confidence interval, 4.83-12.70; P<0.0001) in the resistant cohort. Using metaregression, the falls were larger in trials that did not use ambulatory blood pressure monitoring as an inclusion criterion (z=2.84; P=0.0045), in those with higher baseline blood pressures (z=-0.3; P=0.0001), and in those where the patients were prescribed a continuous background of antihypertensives (z=-2.72; P=0.0065). The nontrivial magnitude of these apparent blood pressure reductions with perfectly ineffective intervention (placebo) illustrates that efficacy explorations of novel therapies for hypertension, once safety is established, should be performed with a randomized, appropriately controlled, and blinded design. © 2014 American Heart Association, Inc.

Why all randomised controlled trials produce biased results.

PubMed

Krauss, Alexander

2018-06-01

Randomised controlled trials (RCTs) are commonly viewed as the best research method to inform public health and social policy. Usually they are thought of as providing the most rigorous evidence of a treatment's effectiveness without strong assumptions, biases and limitations. This is the first study to examine that hypothesis by assessing the 10 most cited RCT studies worldwide. These 10 RCT studies with the highest number of citations in any journal (up to June 2016) were identified by searching Scopus (the largest database of peer-reviewed journals). This study shows that these world-leading RCTs that have influenced policy produce biased results by illustrating that participants' background traits that affect outcomes are often poorly distributed between trial groups, that the trials often neglect alternative factors contributing to their main reported outcome and, among many other issues, that the trials are often only partially blinded or unblinded. The study here also identifies a number of novel and important assumptions, biases and limitations not yet thoroughly discussed in existing studies that arise when designing, implementing and analysing trials. Researchers and policymakers need to become better aware of the broader set of assumptions, biases and limitations in trials. Journals need to also begin requiring researchers to outline them in their studies. We need to furthermore better use RCTs together with other research methods. Key messages RCTs face a range of strong assumptions, biases and limitations that have not yet all been thoroughly discussed in the literature. This study assesses the 10 most cited RCTs worldwide and shows that trials inevitably produce bias. Trials involve complex processes - from randomising, blinding and controlling, to implementing treatments, monitoring participants etc. - that require many decisions and steps at different levels that bring their own assumptions and degree of bias to results.

Randomized controlled trials in children's heart surgery in the 21st century: a systematic review.

PubMed

Drury, Nigel E; Patel, Akshay J; Oswald, Nicola K; Chong, Cher-Rin; Stickley, John; Barron, David J; Jones, Timothy J

2018-04-01

Randomized controlled trials are the gold standard for evaluating health care interventions, yet are uncommon in children's heart surgery. We conducted a systematic review of clinical trials in paediatric cardiac surgery to evaluate the scope and quality of the current international literature. We searched MEDLINE, CENTRAL and LILACS, and manually screened retrieved references and systematic reviews to identify all randomized controlled trials reporting the effect of any intervention on the conduct or outcomes of heart surgery in children published in any language since January 2000; secondary publications and those reporting inseparable adult data were excluded. Two reviewers independently screened studies for eligibility and extracted data; the Cochrane Risk of Bias tool was used to assess for potential biases. We identified 333 trials from 34 countries randomizing 23 902 children. Most were early phase (313, 94.0%), recruiting few patients (median 45, interquartile range 28-82), and only 11 (3.3%) directly evaluated a surgical intervention. One hundred and nine (32.7%) trials calculated a sample size, 52 (15.6%) reported a CONSORT diagram, 51 (15.3%) were publicly registered and 25 (7.5%) had a Data Monitoring Committee. The overall risk of bias was low in 22 (6.6%), high in 69 (20.7%) and unclear in 242 (72.7%). The recent literature in children's heart surgery contains few late-phase clinical trials. Most trials did not conform to the accepted standards of reporting, and the overall risk of bias was low in few studies. There is a need for high-quality, multicentre clinical trials to provide a robust evidence base for contemporary paediatric cardiac surgical practice.

Randomized controlled trials in children’s heart surgery in the 21st century: a systematic review

PubMed Central

Drury, Nigel E; Patel, Akshay J; Oswald, Nicola K; Chong, Cher-Rin; Stickley, John; Barron, David J; Jones, Timothy J

2018-01-01

Abstract OBJECTIVES Randomized controlled trials are the gold standard for evaluating health care interventions, yet are uncommon in children’s heart surgery. We conducted a systematic review of clinical trials in paediatric cardiac surgery to evaluate the scope and quality of the current international literature. METHODS We searched MEDLINE, CENTRAL and LILACS, and manually screened retrieved references and systematic reviews to identify all randomized controlled trials reporting the effect of any intervention on the conduct or outcomes of heart surgery in children published in any language since January 2000; secondary publications and those reporting inseparable adult data were excluded. Two reviewers independently screened studies for eligibility and extracted data; the Cochrane Risk of Bias tool was used to assess for potential biases. RESULTS We identified 333 trials from 34 countries randomizing 23 902 children. Most were early phase (313, 94.0%), recruiting few patients (median 45, interquartile range 28–82), and only 11 (3.3%) directly evaluated a surgical intervention. One hundred and nine (32.7%) trials calculated a sample size, 52 (15.6%) reported a CONSORT diagram, 51 (15.3%) were publicly registered and 25 (7.5%) had a Data Monitoring Committee. The overall risk of bias was low in 22 (6.6%), high in 69 (20.7%) and unclear in 242 (72.7%). CONCLUSIONS The recent literature in children’s heart surgery contains few late-phase clinical trials. Most trials did not conform to the accepted standards of reporting, and the overall risk of bias was low in few studies. There is a need for high-quality, multicentre clinical trials to provide a robust evidence base for contemporary paediatric cardiac surgical practice. PMID:29186478

Developing a core outcome set for chronic rhinosinusitis: a systematic review of outcomes utilised in the current literature.

PubMed

Soni-Jaiswal, Archana; Lakhani, Raj; Hopkins, Claire

2017-07-11

A core outcome set (COS) is an agreed standardised collection of outcomes that should be measured and reported by all trials for a specific clinical area, in this case chronic rhinosinusitis. These are not restrictive and researchers may continue to explore other outcomes alongside these that they feel are relevant to their intervention. The aim of this systematic review was to identify the need for a COS for chronic rhinosinusitis. A sensitive search strategy was used to identify all published Cochrane systematic reviews and randomised control trials of intervention for adult patients with chronic rhinosinusitis. Two independent authors reviewed these to obtain a list of outcomes and outcome measures reported by each clinical trial. Sixty-nine randomised control trials and eight Cochrane systematic reviews were included in this study. They reported 68 individual outcomes and outcome measures, with an average of four to ten outcomes per clinical trial. These outcomes were mapped to 23 subcategories belonging to eight core categories. The key finding of this review was the heterogeneity of outcomes reported and measured by clinical trials of patients with chronic rhinosinusitis, precluding meaningful meta-analysis of data. This review supports the need for development of a COS, to be used in future trials on adult patients with chronic rhinosinusitis.

Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review

PubMed Central

Kirksey, Meghan A.; Haskins, Stephen C.; Cheng, Jennifer; Liu, Spencer S.

2015-01-01

Background The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants. Objectives To systematically review adjuvant-related randomized controlled trials and meta-analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks. Methods Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and published without an Investigational New Drug application or equivalent status were excluded. Results Sixty one novel clinical trials and meta-analyses were identified and included in this review. The clinical trials reported analgesic duration data for the following adjuvants: buprenorphine (6), morphine (6), fentanyl (10), epinephrine (3), clonidine (7), dexmedetomidine (7), dexamethasone (7), tramadol (8), and magnesium (4). Studies of perineural buprenorphine, clonidine, dexamethasone, dexmedetomidine, and magnesium most consistently demonstrated prolongation of peripheral nerve blocks. Conclusions Buprenorphine, clonidine, dexamethasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and concerns for side effects and potential toxicity persist. PMID:26355598

Protocol for the 'e-Nudge trial': a randomised controlled trial of electronic feedback to reduce the cardiovascular risk of individuals in general practice [ISRCTN64828380

PubMed Central

Holt, Tim A; Thorogood, Margaret; Griffiths, Frances; Munday, Stephen

2006-01-01

Background Cardiovascular disease (including coronary heart disease and stroke) is a major cause of death and disability in the United Kingdom, and is to a large extent preventable, by lifestyle modification and drug therapy. The recent standardisation of electronic codes for cardiovascular risk variables through the United Kingdom's new General Practice contract provides an opportunity for the application of risk algorithms to identify high risk individuals. This randomised controlled trial will test the benefits of an automated system of alert messages and practice searches to identify those at highest risk of cardiovascular disease in primary care databases. Design Patients over 50 years old in practice databases will be randomised to the intervention group that will receive the alert messages and searches, and a control group who will continue to receive usual care. In addition to those at high estimated risk, potentially high risk patients will be identified who have insufficient data to allow a risk estimate to be made. Further groups identified will be those with possible undiagnosed diabetes, based either on elevated past recorded blood glucose measurements, or an absence of recent blood glucose measurement in those with established cardiovascular disease. Outcome measures The intervention will be applied for two years, and outcome data will be collected for a further year. The primary outcome measure will be the annual rate of cardiovascular events in the intervention and control arms of the study. Secondary measures include the proportion of patients at high estimated cardiovascular risk, the proportion of patients with missing data for a risk estimate, and the proportion with undefined diabetes status at the end of the trial. PMID:16646967

Lack of diversity in orthopaedic trials conducted in the United States.

PubMed

Somerson, Jeremy S; Bhandari, Mohit; Vaughan, Clayton T; Smith, Christopher S; Zelle, Boris A

2014-04-02

Several orthopaedic studies have suggested patient race and ethnicity to be important predictors of patient functional outcomes. This issue has also been emphasized by federal funding sources. However, the reporting of race and ethnicity has gained little attention in the orthopaedic literature. The objective of this study was to determine the percentage of orthopaedic randomized controlled clinical trials in the United States that included race and ethnicity data and to record the racial and ethnic distribution of patients enrolled in these trials. A systematic review of orthopaedic randomized controlled trials published from 2008 to 2011 was performed. The studies were identified through a manual search of thirty-two scientific journals, including all major orthopaedic journals as well as five leading medical journals. Only trials from the United States were included. The publication date, journal impact factor, orthopaedic subspecialty, ZIP code of the primary research site, number of enrolled patients, type of funding, and race and ethnicity of the study population were extracted from the identified studies. A total of 158 randomized controlled trials with 37,625 enrolled patients matched the inclusion criteria. Only thirty-two studies (20.3%) included race or ethnicity with at least one descriptor. Government funding significantly increased the likelihood of reporting these factors (p < 0.05). The percentages of Hispanic and African-American patients were extractable for studies with 7648 and 6591 enrolled patients, respectively. In those studies, 4.6% (352) of the patients were Hispanic and 6.2% (410) were African-American; these proportions were 3.5-fold and twofold lower, respectively, than those represented in the 2010 United States Census. Few orthopaedic randomized controlled trials performed in the United States reported data on race or ethnicity. Among trials that did report demographic race or ethnicity data, the inclusion of minority patients was substantially lower than would be expected on the basis of census demographics. Failure to represent the true racial diversity may result in decreased generalizability of trial conclusions across clinical populations.

Safety and efficacy of fenproporex for obesity treatment: a systematic review

PubMed Central

Paumgartten, Francisco José Roma; Pereira, Sabrina Schaaf Teixeira Costa; de Oliveira, Ana Cecilia Amado Xavier

2016-01-01

ABSTRACT OBJECTIVE To evaluate clinical evidence on the safety and efficacy of fenproporex for treating obesity. METHODS MEDLINE, LILACS and Cochrane Controlled Trials Register were searched as well as references cited by articles and relevant documents. Two authors independently assessed the studies for inclusion and regarding risk of bias, collected data, and accuracy. Eligible studies were all those placebo-controlled that provided data on the efficacy and safety of Fenproporex to treat obesity. RESULTS Only four controlled studies met the inclusion criteria. One randomized, placebo-controlled trial on Fenproporex was found on electronic databases. Three placebo-controlled studies (in non-indexed journals) were identified by hand-searching. Patients with cardiovascular and other comorbidities were excluded in all studies. Trials lasted from 40 to 364 days and doses ranged from 20 to 33.6 mg/d. All controlled studies found that weight loss among Fenproporex-treated patients was greater than that produced by the placebo, but drug effect was modest. Fenproporex produced additional weight reductions of 4.7 kg (one year), 3.8 kg (six months) and 1.55 kg (two months) in average, in relation to diet and exercise only (three trials). Insomnia, irritability, and anxiety were the most frequently reported side effects in the four studies. CONCLUSIONS There is a paucity of randomized, placebo-controlled trials on Fenproporex and those identified here present major methodological flaws. These studies suggest that Fenproporex is modestly effective in promoting weight loss. Nonetheless, they failed to provide evidence that it reduces obesity-associated morbidity and mortality. Data from these studies are insufficient to determine the risk-benefit profile of Fenproporex. Abuse potential and amphetamine-like adverse effects are causes for concern. PMID:27253901

A Mock Randomized Controlled Trial With Audience Response Technology for Teaching and Learning Epidemiology.

PubMed

Baker, Philip R A; Francis, Daniel P; Cathcart, Abby

2017-04-01

The study's objective was to apply and assess an active learning approach to epidemiology and critical appraisal. Active learning comprised a mock, randomized controlled trial (RCT) conducted with learners in 3 countries. The mock trial consisted of blindly eating red Smarties candy (intervention) compared to yellow Smarties (control) to determine whether red Smarties increase happiness. Audience response devices were employed with the 3-fold purposes to produce outcome data for analysis of the effects of red Smarties, identify baseline and subsequent changes in participant's knowledge and confidence in understanding of RCTs, and assess the teaching approach. Of those attending, 82% (117 of 143 learners) participated in the trial component. Participating in the mock trial was a positive experience, and the use of the technology aided learning. The trial produced data that learners analyzed in "real time" during the class. The mock RCT is a fun and engaging approach to teaching RCTs and helping students to develop skills in critical appraisal.

Transabdominal amnioinfusion for preterm premature rupture of membranes: a systematic review and metaanalysis of randomized and observational studies.

PubMed

Porat, Shay; Amsalem, Hagai; Shah, Prakesh S; Murphy, Kellie E

2012-11-01

The purpose of this study was to review systematically the efficacy of transabdominal amnioinfusion (TA) in early preterm premature rupture of membranes (PPROM). We conducted a literature search of EMBASE, MEDLINE, and ClinicalTrials.gov databases and identified studies in which TA was used in cases of proven PPROM and oligohydramnios. Risk of bias was assessed for observational studies and randomized controlled trials. Primary outcomes were latency period and perinatal mortality rates. Four observational studies (n = 147) and 3 randomized controlled trials (n = 165) were eligible. Pooled latency period was 14.4 (range, 8.2-20.6) and 11.41 (range -3.4 to 26.2) days longer in the TA group in the observational and the randomized controlled trials, respectively. Perinatal mortality rates were reduced among the treatment groups in both the observational studies (odds ratio, 0.12; 95% confidence interval, 0.02-0.61) and the randomized controlled trials (odds ratio, 0.33; 95% confidence interval, 0.10-1.12). Serial TA for early PPROM may improve early PPROM-associated morbidity and mortality rates. Additional adequately powered randomized control trials are needed. Copyright © 2012 Mosby, Inc. All rights reserved.

Point-of-care cluster randomized trial in stroke secondary prevention using electronic health records.

PubMed

Dregan, Alex; van Staa, Tjeerd P; McDermott, Lisa; McCann, Gerard; Ashworth, Mark; Charlton, Judith; Wolfe, Charles D A; Rudd, Anthony; Yardley, Lucy; Gulliford, Martin C; Trial Steering Committee

2014-07-01

The aim of this study was to evaluate whether the remote introduction of electronic decision support tools into family practices improves risk factor control after first stroke. This study also aimed to develop methods to implement cluster randomized trials in stroke using electronic health records. Family practices were recruited from the UK Clinical Practice Research Datalink and allocated to intervention and control trial arms by minimization. Remotely installed, electronic decision support tools promoted intensified secondary prevention for 12 months with last measure of systolic blood pressure as the primary outcome. Outcome data from electronic health records were analyzed using marginal models. There were 106 Clinical Practice Research Datalink family practices allocated (intervention, 53; control, 53), with 11 391 (control, 5516; intervention, 5875) participants with acute stroke ever diagnosed. Participants at trial practices had similar characteristics as 47,887 patients with stroke at nontrial practices. During the intervention period, blood pressure values were recorded in the electronic health records for 90% and cholesterol values for 84% of participants. After intervention, the latest mean systolic blood pressure was 131.7 (SD, 16.8) mm Hg in the control trial arm and 131.4 (16.7) mm Hg in the intervention trial arm, and adjusted mean difference was -0.56 mm Hg (95% confidence interval, -1.38 to 0.26; P=0.183). The financial cost of the trial was approximately US $22 per participant, or US $2400 per family practice allocated. Large pragmatic intervention studies may be implemented at low cost by using electronic health records. The intervention used in this trial was not found to be effective, and further research is needed to develop more effective intervention strategies. http://www.controlled-trials.com. Current Controlled Trials identifier: ISRCTN35701810. © 2014 American Heart Association, Inc.

Indexing of randomised controlled trials of physiotherapy interventions: a comparison of AMED, CENTRAL, CINAHL, EMBASE, hooked on evidence, PEDro, PsycINFO and PubMed.

PubMed

Moseley, Anne M; Sherrington, Catherine; Elkins, Mark R; Herbert, Robert D; Maher, Christopher G

2009-09-01

To compare the comprehensiveness of indexing the reports of randomised controlled trials of physiotherapy interventions by eight bibliographic databases (AMED, CENTRAL, CINAHL, EMBASE, Hooked on Evidence, PEDro, PsycINFO and PubMed). Audit of bibliographic databases. Two hundred and eighty-one reports of randomised controlled trials of physiotherapy interventions were identified by screening the reference lists of 30 relevant systematic reviews published in four consecutive issues of the Cochrane Database of Systematic Reviews (Issue 3, 2007 to Issue 2, 2008). AMED, CENTRAL, CINAHL, EMBASE, Hooked on Evidence, PEDro, PsycINFO and PubMed were used to search for the trial reports. The number of trial reports indexed in each database was calculated. PEDro indexed 99% of the trial reports, CENTRAL indexed 98%, PubMed indexed 91%, EMBASE indexed 82%, CINAHL indexed 61%, Hooked on Evidence indexed 40%, AMED indexed 36% and PsycINFO indexed 17%. Most trial reports (92%) were indexed on four or more of the databases. One trial report was indexed on a single database (PEDro). Of the eight bibliographic databases examined, PEDro and CENTRAL provide the most comprehensive indexing of reports of randomised trials of physiotherapy interventions.

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.

Orthodontic treatment in periodontitis‐susceptible subjects: a systematic literature review

PubMed Central

Lindsten, Rune; Slotte, Christer; Bjerklin, Krister

2016-01-01

Abstract The aim is to evaluate the literature for clinical scientific data on possible effects of orthodontic treatment on periodontal status in periodontitis‐susceptible subjects. A systematic literature review was performed on studies in English using PubMed, MEDLINE, and Cochrane Library central databases (1965‐2014). By manually searching reference lists of selected studies, we identified additional articles; then we searched these publications: Journal of Periodontology, Periodontology 2000, Journal of Clinical Periodontology, American Journal of Orthodontics and Dentofacial Orthopedics, Angle Orthodontist, International Journal of Periodontics & Restorative Dentistry, and European Journal of Orthodontics. Search terms included randomized clinical trials, controlled clinical trials, prospective and retrospective clinical studies, case series >5 patients, periodontitis, orthodontics, alveolar bone loss, tooth migration, tooth movement, orthodontic extrusion, and orthodontic intrusion. Only studies on orthodontic treatment in periodontally compromised dentitions were included. One randomized controlled clinical trial, one controlled clinical trial, and 12 clinical studies were included. No evidence currently exists from controlled studies and randomized controlled clinical trials, which shows that orthodontic treatment improves or aggravates the status of periodontally compromised dentitions. PMID:29744163

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.

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.

A systematic review of Investigator Global Assessment (IGA) in atopic dermatitis (AD) trials: Many options, no standards.

PubMed

Futamura, Masaki; Leshem, Yael A; Thomas, Kim S; Nankervis, Helen; Williams, Hywel C; Simpson, Eric L

2016-02-01

Investigators often use global assessments to provide a snapshot of overall disease severity in dermatologic clinical trials. Although easy to perform, the frequency of use and standardization of global assessments in studies of atopic dermatitis (AD) is unclear. We sought to assess the frequency, definitions, and methods of analysis of Investigator Global Assessment in randomized controlled trials of AD. We conducted a systematic review using all published randomized controlled trials of AD treatments in the Global Resource of Eczema Trials database (2000-2014). We determined the frequency of global scales application and defining features. Among 317 trials identified, 101 trials (32%) used an investigator-performed global assessment as an outcome measure. There was large variability in global assessments between studies in nomenclature, scale size, definitions, outcome description, and analysis. Both static and dynamic scales were identified that ranged from 4- to 7-point scales. North American studies used global assessments more commonly than studies from other countries. The search was restricted to the Global Resource of Eczema Trials database. Global assessments are used frequently in studies of AD, but their complete lack of standardized definitions and implementation preclude any meaningful comparisons between studies, which in turn impedes data synthesis to inform clinical decision-making. Standardization is urgently required. Copyright © 2015. Published by Elsevier Inc.

Searches for Randomized Controlled Trials of Drugs in MEDLINE and EMBASE Using Only Generic Drug Names Compared with Searches Applied in Current Practice in Systematic Reviews

ERIC Educational Resources Information Center

Waffenschmidt, Siw; Guddat, Charlotte

2015-01-01

Background: It is unclear which terms should be included in bibliographic searches for randomized controlled trials (RCTs) of drugs, and identifying relevant drug terms can be extremely laborious. The aim of our analysis was to determine whether a bibliographic search using only the generic drug name produces sufficient results for the generation…

Spinal cord stimulation for cancer-related pain in adults.

PubMed

Peng, Lihua; Min, Su; Zejun, Zhou; Wei, Ke; Bennett, Michael I

2015-06-29

This is an update of a review first published in The Cochrane Library in Issue 3, 2013. Cancer-related pain places a heavy burden on public health with related high expenditure. Severe pain is associated with a decreased quality of life in patients with cancer. A significant proportion of patients with cancer-related pain are under-treated. There is a need for more effective control of cancer-related pain. Spinal cord stimulation (SCS) may have a role in pain management. The effectiveness and safety of SCS for patients with cancer-related pain is currently unknown. This systematic review evaluated the effectiveness of SCS for cancer-related pain compared with standard care using conventional analgesic medication. We also appraised risk and potential adverse events associated with the use of SCS. This is an update of a review first published in The Cochrane Library in Issue 3, 2013. The search strategy for the update was the same as in the original review. We searched the following bibliographic databases in order to identify relevant studies: the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library; MEDLINE; EMBASE; and CBM (Chinese Biomedical Database) in October 2014. We also handsearched relevant journals. There were no language restrictions. We planned to include randomised controlled trials (RCTs) that directly compared SCS with other interventions with regards to the effectiveness of pain management. We also planned to include cross-over trials that compared SCS with another treatment. We planned to identify non-randomised controlled trials but these would only be included if no RCTs could be found. The literature search for the update of this review found 121 potentially eligible articles. The initial search strategy yielded 430 articles. By scrutinising titles and abstracts, we found 412 articles irrelevant to the analytical purpose of this systematic review due to different scopes of diseases or different methods of intervention (intrathecal infusion system; oral medication) or aims other than pain control (spinal cord function monitoring, bladder function restoration or amelioration of organ metabolism). The remaining 18 trials were reviewed as full manuscripts. No RCTs were identified. Fourteen sporadic case reports and review articles were excluded and four before-and-after case series studies (92 participants) were included. Two review authors independently selected the studies to be included in the review according to the prespecified eligibility criteria. A checklist for methodological quality of non-randomised controlled trials was used (STROBE checklist) and all review authors discussed and agreed on the inclusion of trials and the results of the quality assessment. No new studies were identified for inclusion in this update of the review. Four before-and-after case series studies (a total of 92 participants) met our criteria for inclusion in the previous version of the review. All included trials adopted a visual analogue scale (VAS) to evaluate pain relief. Heterogeneity existed in terms of baseline characteristics, electrode and stimulator parameters, level of implantation and route of implantation; each trial reported data differently. In two trials, pain relief was achieved in 76% (48/63) of participants at the end of the follow-up period. In the third trial, pre-procedure VAS was 6 to 9 (mean 7.43 ); the one-month post-implant VAS was 2 to 4 (mean 3.07); the 12-month post-implant VAS was 1 to 3 (mean 2.67). In the fourth trial, the pre-procedure VAS was 6 to 9 (mean 7.07); 1 to 4 (mean 2.67) at one-month; 1 to 4 (mean 1.87) at 12 months. Analgesic use was largely reduced. The main adverse events were infection of sites of implantation, cerebrospinal fluid (CSF) leakage, pain at the sites of electrodes, dislodgement of the electrodes, and system failure; however, the incidence in participants with cancer could not be calculated. Since all trials were small, non-randomised controlled trials, they carried high or unclear risk of all types of bias. Since the first publication of this review, no new studies were identified. Current evidence is insufficient to establish the role of SCS in treating refractory cancer-related pain. Future randomised studies should focus on the implantation of SCS in participants with cancer-related pain.

A systematic review of randomized controlled trials of interventions designed to decrease child abuse in high-risk families

PubMed Central

Levey, Elizabeth J.; Gelaye, Bizu; Bain, Paul; Rondon, Marta B.; Borba, Christina P.C.; Henderson, David C.; Williams, Michelle A.

2017-01-01

Child abuse is a global problem, and parents with histories of childhood abuse are at increased risk of abusing their offspring. The objective of this systematic review is to provide a clear overview of the existing literature of randomized controlled trials evaluating the effectiveness of interventions to prevent child abuse. PubMed, PsychINFO, Web of Science, Sociological Abstracts, and CINAHL were systematically searched and expanded by hand search. This review includes all randomized controlled trials (RCTs) of interventions designed to prevent abuse among mothers identified as high-risk. Of the eight studies identified, only three found statistically significant reductions in abuse by any measure, and only two found reductions in incidents reported to child protective services. While much has been written about child abuse in high-risk families, few RCTs have been performed. Only home visitation has a significant evidence base for reducing child abuse, and the findings vary considerably. Also, data from low- and middle-income countries are limited. PMID:28110205

Hypnosis for procedure-related pain and distress in pediatric cancer patients: a systematic review of effectiveness and methodology related to hypnosis interventions.

PubMed

Richardson, Janet; Smith, Joanna E; McCall, Gillian; Pilkington, Karen

2006-01-01

The aim of this study was to systematically review and critically appraise the evidence on the effectiveness of hypnosis for procedure-related pain and distress in pediatric cancer patients. A comprehensive search of major biomedical and specialist complementary and alternative medicine databases was conducted. Citations were included from the databases' inception to March 2005. Efforts were made to identify unpublished and ongoing research. Controlled trials were appraised using predefined criteria. Clinical commentaries were obtained for each study. Seven randomized controlled clinical trials and one controlled clinical trial were found. Studies report positive results, including statistically significant reductions in pain and anxiety/distress, but a number of methodological limitations were identified. Systematic searching and appraisal has demonstrated that hypnosis has potential as a clinically valuable intervention for procedure-related pain and distress in pediatric cancer patients. Further research into the effectiveness and acceptability of hypnosis for pediatric cancer patients is recommended.

Interventions to Promote Colorectal Cancer Screening: An Integrative Review

PubMed Central

Rawl, Susan M.; Menon, Usha; Burness, Allison; Breslau, Erica S.

2012-01-01

Behavior change interventions to promote colorectal cancer (CRC) screening have targeted people in community and primary care settings, health care providers, and health systems. Randomized controlled trials provide the strongest evidence of intervention efficacy. The purpose of this integrative review was to evaluate trials of CRC screening interventions published between 1997 and 2007 and to identify knowledge gaps and future directions for research. Thirty-three randomized trials that met inclusion criteria were evaluated using a modified version of the TREND criteria. Significant intervention effects were reported in six out of ten trials focused on increasing fecal occult blood testing, four of seven trials focused on sigmoidoscopy or colonoscopy completion, and nine of 16 focused on completion of any screening test. Several effective interventions to promote CRC screening were identified. Future trials need to use theory to guide interventions, examine moderators and mediators, consistently report results, and use comparable outcome measures. PMID:22261002

Comparative efficacy of simultaneous versus sequential multiple health behavior change interventions among adults: A systematic review of randomised trials.

PubMed

James, Erica; Freund, Megan; Booth, Angela; Duncan, Mitch J; Johnson, Natalie; Short, Camille E; Wolfenden, Luke; Stacey, Fiona G; Kay-Lambkin, Frances; Vandelanotte, Corneel

2016-08-01

Growing evidence points to the benefits of addressing multiple health behaviors rather than single behaviors. This review evaluates the relative effectiveness of simultaneous and sequentially delivered multiple health behavior change (MHBC) interventions. Secondary aims were to identify: a) the most effective spacing of sequentially delivered components; b) differences in efficacy of MHBC interventions for adoption/cessation behaviors and lifestyle/addictive behaviors, and; c) differences in trial retention between simultaneously and sequentially delivered interventions. MHBC intervention trials published up to October 2015 were identified through a systematic search. Eligible trials were randomised controlled trials that directly compared simultaneous and sequential delivery of a MHBC intervention. A narrative synthesis was undertaken. Six trials met the inclusion criteria and across these trials the behaviors targeted were smoking, diet, physical activity, and alcohol consumption. Three trials reported a difference in intervention effect between a sequential and simultaneous approach in at least one behavioral outcome. Of these, two trials favoured a sequential approach on smoking. One trial favoured a simultaneous approach on fat intake. There was no difference in retention between sequential and simultaneous approaches. There is limited evidence regarding the relative effectiveness of sequential and simultaneous approaches. Given only three of the six trials observed a difference in intervention effectiveness for one health behavior outcome, and the relatively consistent finding that the sequential and simultaneous approaches were more effective than a usual/minimal care control condition, it appears that both approaches should be considered equally efficacious. PROSPERO registration number: CRD42015027876. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of green tea catechins with or without caffeine on glycemic control in adults: a meta-analysis of randomized controlled trials.

PubMed

Zheng, Xin-Xin; Xu, Yan-Lu; Li, Shao-Hua; Hui, Rutai; Wu, Yong-Jian; Huang, Xiao-Hong

2013-04-01

The effect of green tea catechins (GTCs) with or without caffeine on glycemic control is controversial. We aimed to identify and quantify the effects of GTCs or GTC-caffeine mixtures on glucose metabolism in adults. A comprehensive literature search was conducted to identify relevant trials of GTCs with or without caffeine on markers of glycemic control [fasting blood glucose (FBG), fasting blood insulin (FBI), glycated hemoglobin (Hb A1c), and homeostatic model assessment of insulin resistance (HOMA-IR)]. Weighted mean differences were calculated for net changes by using fixed-effects models. Prespecified subgroup analyses were performed to explore the influence of covariates on net changes in FBG and FBI concentrations. Twenty-two eligible randomized controlled trials with 1584 subjects were identified. Pooled analyses showed that FBG (-1.48 mg/dL; 95% CI: -2.57, -0.40 mg/dL) decreased significantly with GTCs with or without caffeine, whereas FBI (0.04 μU/mL; 95% CI: -0.36, 0.45 μU/mL), Hb A1c (-0.04%; 95% CI: -0.15, 0.08%), and HOMA-IR (-0.05; 95% CI: -0.37, 0.26) did not. Subgroup analyses indicated that the glucose-lowering effect was apparent when the duration of follow-up was over a median of 12 wk. Overall, no significant heterogeneity was detected for FBG, FBI, Hb A1c, or HOMA-IR. The meta-analysis showed that the administration of GTCs with or without caffeine resulted in a significant reduction in FBG. The limited data available on GTCs did not support a positive effect on FBI, Hb A1c, or HOMA-IR. Thus, more large and well-designed trials are needed in the future. This trial was registered at http://www.crd.york.ac.uk/prospero as CRD42012002139.

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.

Systematic Review and Meta-analysis: Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis.

PubMed

Jairath, Vipul; Zou, Guangyong; Parker, Claire E; Macdonald, John K; Mosli, Mahmoud H; Khanna, Reena; Shackelton, Lisa M; Vandervoort, Margaret K; AlAmeel, Turki; Al Beshir, Mohammad; AlMadi, Majid; Al-Taweel, Talal; Atkinson, Nathan S S; Biswas, Sujata; Chapman, Thomas P; Dulai, Parambir S; Glaire, Mark A; Hoekman, Daniel; Koutsoumpas, Andreas; Minas, Elizabeth; Samaan, Mark A; Travis, Simon; D'Haens, Geert; Levesque, Barrett G; Sandborn, William J; Feagan, Brian G

2016-05-01

Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in ulcerative colitis [UC] clinical trials, and factors influencing this are poorly understood. We quantify placebo response and remission rates in UC RCTs and identify trial design factors influencing them. MEDLINE, EMBASE, and the Cochrane Library were searched from inception through April 2014 for placebo-controlled trials in adult patients with UC of a biological agent, corticosteroid, immunosuppressant, or aminosalicylate. Data were independently doubly extracted. Quality was assessed using the Cochrane risk of bias tool. In all, 51 trials [48 induction and 10 maintenance phases] were identified. Placebo response and remission rates were pooled according to random-effects models, and mixed-effects meta-regression models were used to evaluate effects of study-level characteristics on these rates. Pooled estimates of placebo remission and response rates for induction trials were 10% (95% confidence interval [CI] 7-13%) and 33% [95% CI 29-37%], respectively. Corresponding values for maintenance trials were 19% [95% CI 11-30%] and 22% [95% CI 17-28%]. Trials enrolling patients with more active disease confirmed by endoscopy [endoscopy subscore ≥ 2] were associated with lower placebo rates. Conversely, placebo rates increased with increasing trial duration and number of study visits. Objective assessment of greater disease activity at trial entry by endoscopy lowered placebo rates, whereas increasing trial duration and more interactions with healthcare providers increased placebo rates. These findings have important implications for design and conduct of clinical trials. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Hematopoietic stem cell transplantation for people with ß-thalassaemia major.

PubMed

Jagannath, Vanitha A; Fedorowicz, Zbys; Al Hajeri, Amani; Sharma, Akshay

2016-11-30

Thalassemia is an inherited autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions. This results in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In ß-thalassaemia major there is an underproduction of ß-globin chains combined with excess of free α-globin chains. The excess free α-globin chains precipitate in red blood cells, leading to their destruction (haemolysis) and ineffective erythropoiesis. The conventional approach to treatment is based on the correction of haemoglobin status through regular blood transfusions and iron chelation therapy for iron overload. Although conventional treatment has the capacity to improve the quality of life of people with ß-thalassaemia major, allogeneic hematopoietic stem cell transplantation is the only currently available procedure which has the curative potential. This is an update of a previously published Cochrane Review. To evaluate the effectiveness and safety of different types of allogeneic hematopoietic stem cell transplantation, in people with severe transfusion-dependant ß-thalassaemia major, ß-thalassaemia intermedia or ß0/+- thalassaemia variants requiring chronic blood transfusion. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 18 August 2016. Randomised controlled trials and quasi-randomised controlled trials comparing allogeneic hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen). Two review authors independently screened studies and had planned to extract data and assess risk of bias using standard Cochrane methodologies but no studies were identified for inclusion. No relevant studies were retrieved after a comprehensive search of the literature. We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of allogeneic stem cell transplantation in people with severe transfusion-dependant ß-thalassaemia major or ß0/+- thalassaemia variants requiring chronic blood transfusion. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.

Hematopoietic stem cell transplantation for people with ß-thalassaemia major.

PubMed

Jagannath, Vanitha A; Fedorowicz, Zbys; Al Hajeri, Amani; Sharma, Akshay

2014-10-15

Thalassemia is an inherited blood disorder, caused by mutations in regulatory genes and transmitted as an autosomal recessive disorder, which results in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In ß-thalassaemia major there is an underproduction of ß-globin chains combined with excess of free α-globin chains. The excess free α-globin chains damage the red blood cell membranes, leading to their destruction and a phenomenon termed ineffective erythropoiesis. The conventional approach to treatment is based on the correction of haemoglobin status through regular blood transfusions and iron chelation therapy for iron overload. Although conventional treatment has the capacity to improve the quality of life of people with ß-thalassaemia major, allogeneic hematopoietic stem cell transplantation is the only currently available procedure which has the potential to definitively cure the disease. To evaluate the effectiveness and safety of different types of allogeneic hematopoietic stem cell transplantation, in people with severe transfusion-dependant ß-thalassaemia major, ß-thalassaemia intermedia or ß0/+- thalassaemia variants requiring chronic blood transfusion. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 11 November 2013. Randomised controlled trials and quasi-randomised controlled trials comparing allogeneic hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen). Two review authors independently screened studies and had planned to extract data and assess risk of bias using standard Cochrane Collaboration methodologies but no studies were identified for inclusion. No relevant studies were retrieved after a comprehensive search of the literature. We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of allogeneic stem cell transplantation in people with severe transfusion-dependant ß-thalassaemia major or ß0/+- thalassaemia variants requiring chronic blood transfusion. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.

Controlling the invasive diatom Didymosphenia geminata: an ecotoxicity assessment of four potential biocides.

PubMed

Jellyman, P G; Clearwater, S J; Clayton, J S; Kilroy, C; Blair, N; Hickey, C W; Biggs, B J F

2011-07-01

In 2004, an invasive mat-forming freshwater diatom, Didymosphenia geminata (didymo), was found in New Zealand causing concern with regard to potential consequences for local freshwater ecosystems. A four-stage research program was initiated to identify methods to control D. geminata. This article reports the results of Stage 2, in which four potential control compounds [Gemex™ (a chelated copper formulation), EDTA, Hydrothol®191, and Organic Interceptor™ (a pine oil formulation)] selected in Stage 1 were evaluated for their biocidal efficacy on D. geminata and effects on non-target organisms using both artificial stream and laboratory trials. Artificial stream trials evaluated the mortality rates of D. geminata and fishes to three concentrations of the four biocides, whereas laboratory toxicity trials tested the response of green alga and cladocera to a range of biocide concentrations and exposure times. In artificial stream trials, Gemex and Organic Interceptor were the most effective biocides against D. geminata for a number of measured indices; however, exposure of fishes to Organic Interceptor resulted in high mortality rates. Laboratory toxicity testing indicated that Gemex might negatively affect sensitive stream invertebrates, based on the cladoceran sensitivity at the proposed river control dose. A decision support matrix evaluated the four biocides based on nine criteria stipulated by river stakeholders (effectiveness, non-target species impacts, stalk removal, degradation profile, risks to health and safety, ease of application, neutralization potential, cost, and local regulatory requirements) and Gemex was identified as the product warranting further refinement prior to an in-river trial.

Does perioperative ketamine have a role in the prevention of chronic postsurgical pain: the ROCKet trial.

PubMed

Schug, Stephan A; Peyton, Philip

2017-11-01

Identifying operations and individuals with an increased risk of chronic postsurgical pain (CPSP) has led to significant interest in interventions with the potential to achieve primary prevention of this condition. Pharmacological prevention remains controversial with a Cochrane review identifying perioperative ketamine administration as the only intervention with possible benefit although, with only small, heterogeneous studies, the authors called for a large randomised controlled trial (RCT) to confirm the validity of this result. In response to these data, a group of researchers from Australia and Hong Kong designed the ROCKet trial - Reduction Of Chronic Post-surgical Pain with Ketamine, endorsed by the Australian and New Zealand College of Anaesthetists (ANZCA) Clinical Trials Network (CTN).

Industry Bias in Randomized Controlled Trials in General and Abdominal Surgery: An Empirical Study.

PubMed

Probst, Pascal; Knebel, Phillip; Grummich, Kathrin; Tenckhoff, Solveig; Ulrich, Alexis; Büchler, Markus W; Diener, Markus K

2016-07-01

Industry sponsorship has been identified as a source of bias in several fields of medical science. To date, the influence of industry sponsorship in the field of general and abdominal surgery has not been evaluated. A systematic literature search (1985-2014) was performed in the Cochrane Library, MEDLINE, and EMBASE to identify randomized controlled trials in general and abdominal surgery. Information on funding source, outcome, and methodological quality was extracted. Association of industry sponsorship and positive outcome was expressed as odds ratio (OR) with 95% confidence interval (CI). A χ test and a multivariate logistic regression analysis with study characteristics and known sources of bias were performed. A total of 7934 articles were screened and 165 randomized controlled trials were included. No difference in methodological quality was found. Industry-funded trials more often presented statistically significant results for the primary endpoint (OR, 2.44; CI, 1.04-5.71; P = 0.04). Eighty-eight of 115 (76.5%) industry-funded trials and 19 of 50 (38.0%) non-industry-funded trials reported a positive outcome (OR, 5.32; CI, 2.60-10.88; P < 0.001). Industry-funded trials more often reported a positive outcome without statistical justification (OR, 5.79; CI, 2.13-15.68; P < 0.001). In a multivariate analysis, funding source remained significantly associated with reporting of positive outcome (P < 0.001). Industry funding of surgical trials leads to exaggerated positive reporting of outcomes. This study emphasizes the necessity for declaration of funding source. Industry involvement in surgical research has to ensure scientific integrity and independence and has to be based on full transparency.

Contribution of spontaneous improvement to placebo response in depression: a meta-analytic review.

PubMed

Rutherford, Bret R; Mori, Shoko; Sneed, Joel R; Pimontel, Monique A; Roose, Steven P

2012-06-01

It is unknown to what degree spontaneous improvement accounts for the large placebo response observed in antidepressant trials for Major Depressive Disorder (MDD). The purpose of this study was to estimate the spontaneous improvement observed in treatment-seeking individuals with acute MDD by determining the symptom change in depressed patients assigned to wait-list controls in psychotherapy studies. The databases PubMed and PsycINFO were searched to identify randomized, prospective studies randomizing outpatients to psychotherapy or a wait-list control condition for the treatment of acute MDD. Standardized effect sizes calculated from each identified study were aggregated in a meta-analysis to obtain a summary statistic for the change in depression scores during participation in a wait-list control. Ten trials enrolling 340 participants in wait-list control conditions were identified. The estimated effect size for the change in depression scores during wait-list control was 0.505 (95% CI 0.271-0.739, p < 0.001), representing an average improvement of 4 points on the Hamilton Rating Scale for Depression. Depressed patients acutely experience improvement even without treatment, but spontaneous improvement is unlikely to account for the magnitude of placebo response typically observed in antidepressant trials. These findings must be interpreted in light of the small number wait-list control participants available for analysis as well as certain methodological heterogeneity in the psychotherapy studies analyzed. Copyright © 2012 Elsevier Ltd. All rights reserved.

A systematic review of natural health product treatment for vitiligo

PubMed Central

Szczurko, Orest; Boon, Heather S

2008-01-01

Background Vitiligo is a hypopigmentation disorder affecting 1 to 4% of the world population. Fifty percent of cases appear before the age of 20 years old, and the disfigurement results in psychiatric morbidity in 16 to 35% of those affected. Methods Our objective was to complete a comprehensive, systematic review of the published scientific literature to identify natural health products (NHP) such as vitamins, herbs and other supplements that may have efficacy in the treatment of vitiligo. We searched eight databases including MEDLINE and EMBASE for vitiligo, leucoderma, and various NHP terms. Prospective controlled clinical human trials were identified and assessed for quality. Results Fifteen clinical trials were identified, and organized into four categories based on the NHP used for treatment. 1) L-phenylalanine monotherapy was assessed in one trial, and as an adjuvant to phototherapy in three trials. All reported beneficial effects. 2) Three clinical trials utilized different traditional Chinese medicine products. Although each traditional Chinese medicine trial reported benefit in the active groups, the quality of the trials was poor. 3) Six trials investigated the use of plants in the treatment of vitiligo, four using plants as photosensitizing agents. The studies provide weak evidence that photosensitizing plants can be effective in conjunction with phototherapy, and moderate evidence that Ginkgo biloba monotherapy can be useful for vitiligo. 4) Two clinical trials investigated the use of vitamins in the therapy of vitiligo. One tested oral cobalamin with folic acid, and found no significant improvement over control. Another trial combined vitamin E with phototherapy and reported significantly better repigmentation over phototherapy only. It was not possible to pool the data from any studies for meta-analytic purposes due to the wide difference in outcome measures and poor quality ofreporting. Conclusion Reports investigating the efficacy of NHPs for vitiligo exist, but are of poor methodological quality and contain significant reporting flaws. L-phenylalanine used with phototherapy, and oral Ginkgo biloba as monotherapy show promise and warrant further investigation. PMID:18498646

Medial Tibial Stress Syndrome: Evidence-Based Prevention

PubMed Central

Craig, Debbie I

2008-01-01

Reference: Thacker SB, Gilchrist J, Stroup DF, Kimsey CD. The prevention of shin splints in sports: a systematic review of literature. Med Sci Sports Exerc. 2002;34(1):32–40. Clinical Question: Among physically active individuals, which medial tibial stress syndrome (MTSS) prevention methods are most effective to decrease injury rates? Data Sources: Studies were identified by searching MEDLINE (1966–2000), Current Contents (1996–2000), Biomedical Collection (1993–1999), and Dissertation Abstracts. Reference lists of identified studies were searched manually until no further studies were identified. Experts in the field were contacted, including first authors of randomized controlled trials addressing prevention of MTSS. The Cochrane Collaboration (early stage of Cochrane Database of Systematic Reviews) was contacted. Study Selection: Inclusion criteria included randomized controlled trials or clinical trials comparing different MTSS prevention methods with control groups. Excluded were studies that did not provide primary research data or that addressed treatment and rehabilitation rather than prevention of incident MTSS. Data Extraction: A total of 199 citations were identified. Of these, 4 studies compared prevention methods for MTSS. Three reviewers independently scored the 4 studies. Reviewers were blinded to the authors' names and affiliations but not the results. Each study was evaluated independently for methodologic quality using a 100-point checklist. Final scores were averages of the 3 reviewers' scores. Main Results: Prevention methods studied were shock-absorbent insoles, foam heel pads, Achilles tendon stretching, footwear, and graduated running programs. No statistically significant results were noted for any of the prevention methods. Median quality scores ranged from 29 to 47, revealing flaws in design, control for bias, and statistical methods. Conclusions: No current evidence supports any single prevention method for MTSS. The most promising outcomes support the use of shock-absorbing insoles. Well-designed and controlled trials are critically needed to decrease the incidence of this common injury. PMID:18523568

Zonisamide and renal calculi in patients with epilepsy: how big an issue?

PubMed

Wroe, Stephen

2007-08-01

To determine the prevalence of renal calculi in patients treated with zonisamide during randomized, controlled and open-label clinical trials, and from post-marketing surveillance data. Reports of renal calculi from four placebo-controlled double-blind trials of zonisamide, their long-term open-label treatment extension phases, and the US/European zonisamide clinical trial programme were reviewed. One double-blind study and its extension included routine ultrasound screening to identify asymptomatic calculi. Post-marketing surveillance data were also investigated, as was concomitant treatment with topiramate. No symptomatic renal calculi were reported during four randomized double-blind, placebo-controlled trials involving 848 subjects (including 498 zonisamide recipients) treated for up to 3 months. In long-term extension studies with treatment for up to 24 months, symptomatic renal calculi were reported in 9/626 (1.4%) patients. Pooled safety data from all US/European clinical trials identified 15/1296 (1.2%) patients with symptomatic renal calculi during treatment for up to 8.7 years. Post-marketing surveillance revealed nine cases from 59 667 patient-years of exposure in the USA, and 14 from 709 294 patient-years of exposure in Japan; only one case occurred during concomitant topiramate and zonisamide treatment. No imbalance in electrolyte levels was found from 35 patients receiving such co-treatment in clinical trials. The available data suggest that the risk of developing renal calculi during zonisamide treatment is low. Data are insufficient to determine whether concomitant treatment with topiramate increases the risk of renal stones.

Are There Scenarios When the Use of Non-Placebo-Control Groups in Experimental Trial Designs Increase Expected Value to Society?

PubMed

Uyei, Jennifer; Braithwaite, R Scott

2016-01-01

Despite the benefits of the placebo-controlled trial design, it is limited by its inability to quantify total benefits and harms. Such trials, for example, are not designed to detect an intervention's placebo or nocebo effects, which if detected could alter the benefit-to-harm balance and change a decision to adopt or reject an intervention. In this article, we explore scenarios in which alternative experimental trial designs, which differ in the type of control used, influence expected value across a range of pretest assumptions and study sample sizes. We developed a decision model to compare 3 trial designs and their implications for decision making: 2-arm placebo-controlled trial ("placebo-control"), 2-arm intervention v. do nothing trial ("null-control"), and an innovative 3-arm trial design: intervention v. do nothing v. placebo trial ("novel design"). Four scenarios were explored regarding particular attributes of a hypothetical intervention: 1) all benefits and no harm, 2) no biological effect, 3) only biological effects, and 4) surreptitious harm (no biological benefit or nocebo effect). Scenario 1: When sample sizes were very small, the null-control was preferred, but as sample sizes increased, expected value of all 3 designs converged. Scenario 2: The null-control was preferred regardless of sample size when the ratio of placebo to nocebo effect was >1; otherwise, the placebo-control was preferred. Scenario 3: When sample size was very small, the placebo-control was preferred when benefits outweighed harms, but the novel design was preferred when harms outweighed benefits. Scenario 4: The placebo-control was preferred when harms outweighed placebo benefits; otherwise, preference went to the null-control. Scenarios are hypothetical, study designs have not been tested in a real-world setting, blinding is not possible in all designs, and some may argue the novel design poses ethical concerns. We identified scenarios in which alternative experimental study designs would confer greater expected value than the placebo-controlled trial design. The likelihood and prevalence of such situations warrant further study. © The Author(s) 2015.

Risk of bias assessment of randomised controlled trials in high-impact ophthalmology journals and general medical journals: a systematic review.

PubMed

Joksimovic, Lazar; Koucheki, Robert; Popovic, Marko; Ahmed, Yusuf; Schlenker, Matthew B; Ahmed, Iqbal Ike K

2017-10-01

Evidence-based treatments in ophthalmology are often based on the results of randomised controlled trials. Biased conclusions from randomised controlled trials may lead to inappropriate management recommendations. This systematic review investigates the prevalence of bias risk in randomised controlled trials published in high-impact ophthalmology journals and ophthalmology trials from general medical journals. Using Ovid MEDLINE, randomised controlled trials in the top 10 high-impact ophthalmology journals in 2015 were systematically identified and critically appraised for the prevalence of bias risk. Included randomised controlled trials were assessed in all domains of bias as defined by the Cochrane Collaboration. In addition, the prevalence of conflict of interest and industry sponsorship was investigated. A comparison with ophthalmology articles from high-impact general medical journals was performed. Of the 259 records that were screened from ophthalmology-specific journals, 119 trials met all inclusion criteria and were critically appraised. In total, 29.4% of domains had an unclear risk, 13.8% had a high risk and 56.8% had a low risk of bias. In comparison, ophthalmology articles from general medical journals had a lower prevalence of unclear risk (17.1%), higher prevalence of high risk (21.9%) and a higher prevalence of low risk domains (61.9%). Furthermore, 64.7% of critically appraised trials from ophthalmology-specific journals did not report any conflicts of interest, while 70.6% did not report an industry sponsor of their trial. In closing, it is essential that authors, peer reviewers and readers closely follow published risk of bias guidelines. © 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.

Predictors of exercise capacity following exercise-based rehabilitation in patients with coronary heart disease and heart failure: A meta-regression analysis.

PubMed

Uddin, Jamal; Zwisler, Ann-Dorthe; Lewinter, Christian; Moniruzzaman, Mohammad; Lund, Ken; Tang, Lars H; Taylor, Rod S

2016-05-01

The aim of this study was to undertake a comprehensive assessment of the patient, intervention and trial-level factors that may predict exercise capacity following exercise-based rehabilitation in patients with coronary heart disease and heart failure. Meta-analysis and meta-regression analysis. Randomized controlled trials of exercise-based rehabilitation were identified from three published systematic reviews. Exercise capacity was pooled across trials using random effects meta-analysis, and meta-regression used to examine the association between exercise capacity and a range of patient (e.g. age), intervention (e.g. exercise frequency) and trial (e.g. risk of bias) factors. 55 trials (61 exercise-control comparisons, 7553 patients) were included. Following exercise-based rehabilitation compared to control, overall exercise capacity was on average 0.95 (95% CI: 0.76-1.41) standard deviation units higher, and in trials reporting maximum oxygen uptake (VO2max) was 3.3 ml/kg.min(-1) (95% CI: 2.6-4.0) higher. There was evidence of a high level of statistical heterogeneity across trials (I(2) statistic > 50%). In multivariable meta-regression analysis, only exercise intervention intensity was found to be significantly associated with VO2max (P = 0.04); those trials with the highest average exercise intensity had the largest mean post-rehabilitation VO2max compared to control. We found considerable heterogeneity across randomized controlled trials in the magnitude of improvement in exercise capacity following exercise-based rehabilitation compared to control among patients with coronary heart disease or heart failure. Whilst higher exercise intensities were associated with a greater level of post-rehabilitation exercise capacity, there was no strong evidence to support other intervention, patient or trial factors to be predictive. © The European Society of Cardiology 2015.

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.

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.

Sub-Lexical Reading Intervention in a Student with Dyslexia and Asperger's Disorder

ERIC Educational Resources Information Center

Wright, Craig; Conlon, Elizabeth; Wright, Michalle; Dyck, Murray

2011-01-01

Dyslexia is a common presenting condition in clinic and educational settings. Unlike the homogenous groups used in randomised trials, educators typically manage children who have multiple developmental problems. Investigations are required into how these complex cases respond to treatment identified as efficacious by controlled trials. This study…

A systematic review of studies of web portals for patients with diabetes mellitus.

PubMed

Coughlin, Steven S; Williams, Lovoria B; Hatzigeorgiou, Christos

2017-01-01

Patient web portals are password-protected online websites that offer patients 24-hour access to personal health information from anywhere with an Internet connection. Due to advances in health information technologies, there has been increasing interest among providers and researchers in patient web portals for use by patients with diabetes and other chronic conditions. This article, which is based upon bibliographic searches in PubMed, reviews web portals for patients with diabetes mellitus including patient web portals tethered to electronic medical records and web portals developed specifically for patients with diabetes. Twelve studies of the impact of patient web portals on the management of diabetes patients were identified. Three had a cross-sectional design, 1 employed mixed-methods, one had a matched-control design, 3 had a retrospective cohort design, and 5 were randomized controlled trials. Six (50%) of the studies examined web portals tethered to electronic medical records and the remainder were web portals developed specifically for diabetes patients. The results of this review suggest that secure messaging between adult diabetic patients and their clinician is associated with improved glycemic control. However, results from observational studies indicate that many diabetic patients do not take advantage of web portal features such as secure messaging, perhaps because of a lack of internet access or lack of experience in navigating web portal resources. Although results from randomized controlled trials provide stronger evidence of the efficacy of web portal use in improving glycemic control among diabetic patients, the number of trials is small and results from the trials have been mixed. Studies suggest that secure messaging between adult diabetic patients and their clinician is associated with improved glycemic control, but negative findings have also been reported. The number of randomized controlled trials that have examined the efficacy of web portal use in improving glycemic control among diabetic patients is still small. Additional research is needed to identify specific portal features that may impact quality of care or improve glycemic control.

A systematic review of studies of web portals for patients with diabetes mellitus

PubMed Central

Williams, Lovoria B.; Hatzigeorgiou, Christos

2017-01-01

Patient web portals are password-protected online websites that offer patients 24-hour access to personal health information from anywhere with an Internet connection. Due to advances in health information technologies, there has been increasing interest among providers and researchers in patient web portals for use by patients with diabetes and other chronic conditions. This article, which is based upon bibliographic searches in PubMed, reviews web portals for patients with diabetes mellitus including patient web portals tethered to electronic medical records and web portals developed specifically for patients with diabetes. Twelve studies of the impact of patient web portals on the management of diabetes patients were identified. Three had a cross-sectional design, 1 employed mixed-methods, one had a matched-control design, 3 had a retrospective cohort design, and 5 were randomized controlled trials. Six (50%) of the studies examined web portals tethered to electronic medical records and the remainder were web portals developed specifically for diabetes patients. The results of this review suggest that secure messaging between adult diabetic patients and their clinician is associated with improved glycemic control. However, results from observational studies indicate that many diabetic patients do not take advantage of web portal features such as secure messaging, perhaps because of a lack of internet access or lack of experience in navigating web portal resources. Although results from randomized controlled trials provide stronger evidence of the efficacy of web portal use in improving glycemic control among diabetic patients, the number of trials is small and results from the trials have been mixed. Studies suggest that secure messaging between adult diabetic patients and their clinician is associated with improved glycemic control, but negative findings have also been reported. The number of randomized controlled trials that have examined the efficacy of web portal use in improving glycemic control among diabetic patients is still small. Additional research is needed to identify specific portal features that may impact quality of care or improve glycemic control. PMID:28736732

Enhancing access to reports of randomized trials published world-wide – the contribution of EMBASE records to the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library

PubMed Central

Lefebvre, Carol; Eisinga, Anne; McDonald, Steve; Paul, Nina

2008-01-01

Background Randomized trials are essential in assessing the effects of healthcare interventions and are a key component in systematic reviews of effectiveness. Searching for reports of randomized trials in databases is problematic due to the absence of appropriate indexing terms until the 1990s and inconsistent application of these indexing terms thereafter. Objectives The objectives of this study are to devise a search strategy for identifying reports of randomized trials in EMBASE which are not already indexed as trials in MEDLINE and to make these reports easily accessible by including them in the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, with the permission of Elsevier, the publishers of EMBASE. Methods A highly sensitive search strategy was designed for EMBASE based on free-text and thesaurus terms which occurred frequently in the titles, abstracts, EMTREE terms (or some combination of these) of reports of trials indexed in EMBASE. This search strategy was run against EMBASE from 1980 to 2005 (1974 to 2005 for four of the terms) and records retrieved by the search, which were not already indexed as randomized trials in MEDLINE, were downloaded from EMBASE, printed and read. An analysis of the language of publication was conducted for the reports of trials published in 2005 (the most recent year completed at the time of this study). Results Twenty-two search terms were used (including nine which were later rejected due to poor cumulative precision). More than a third of a million records were downloaded and scanned and approximately 80,000 reports of trials were identified which were not already indexed as randomized trials in MEDLINE. These are now easily identifiable in CENTRAL, in The Cochrane Library. Cumulative sensitivity ranged from 0.1% to 60% and cumulative precision ranged from 8% to 61%. The truncated term 'random$' identified 60% of the total number of reports of trials but only 35% of the more than 130,000 records retrieved by this term were reports of trials. The language analysis for the sample year 2005 indicated that of the 18,427 reports indexed as randomized trials in MEDLINE, 959 (5%) were in languages other than English. The EMBASE search identified an additional 658 reports in languages other than English, of which the highest number were in Chinese (320). Conclusion The results of the search to date have greatly increased access to reports of trials in EMBASE, especially in some languages other than English. The search strategy used was subjectively derived from a small 'gold standard' set of test records and was not validated in an independent test set. We intend to design an objectively-derived validated search strategy using logistic regression based on the frequency of occurrence of terms in the approximately 80,000 reports of randomized trials identified compared with the frequency of these terms across the entire EMBASE database. PMID:18826567

Cinnamon for diabetes mellitus.

PubMed

Leach, Matthew J; Kumar, Saravana

2012-09-12

Diabetes mellitus is a chronic metabolic disorder that is associated with an increased risk of cardiovascular disease, retinopathy, nephropathy, neuropathy, sexual dysfunction and periodontal disease. Improvements in glycaemic control may help to reduce the risk of these complications. Several animal studies show that cinnamon may be effective in improving glycaemic control. While these effects have been explored in humans also, findings from these studies have not yet been systematically reviewed. To evaluate the effects of cinnamon in patients with diabetes mellitus. Pertinent randomised controlled trials were identified through AARP Ageline, AMED, AMI, BioMed Central gateway, CAM on PubMed, CINAHL, Dissertations Abstracts International, EMBASE, Health Source Nursing/Academic edition, International Pharmaceutical Abstracts, MEDLINE, Natural medicines comprehensive database, The Cochrane Library and TRIP database. Clinical trial registers and the reference lists of included trials were searched also (all up to January 2012). Content experts and manufacturers of cinnamon extracts were also contacted. All randomised controlled trials comparing the effects of orally administered monopreparations of cinnamon (Cinnamomum spp.) to placebo, active medication or no treatment in persons with either type 1 or type 2 diabetes mellitus. Two review authors independently selected trials, assessed risk of bias and trial quality, and extracted data. We contacted study authors for missing information. Ten prospective, parallel-group design, randomised controlled trials, involving a total of 577 participants with type 1 and type 2 diabetes mellitus, were identified. Risk of bias was high or unclear in all but two trials, which were assessed as having moderate risk of bias. Risk of bias in some domains was high in 50% of trials. Oral monopreparations of cinnamon (predominantly Cinnamomum cassia) were administered at a mean dose of 2 g daily, for a period ranging from 4 to 16 weeks. The effect of cinnamon on fasting blood glucose level was inconclusive. No statistically significant difference in glycosylated haemoglobin A1c (HbA1c), serum insulin or postprandial glucose was found between cinnamon and control groups. There were insufficient data to pool results for insulin sensitivity. No trials reported health-related quality of life, morbidity, mortality or costs. Adverse reactions to oral cinnamon were infrequent and generally mild in nature. There is insufficient evidence to support the use of cinnamon for type 1 or type 2 diabetes mellitus. Further trials, which address the issues of allocation concealment and blinding, are now required. The inclusion of other important endpoints, such as health-related quality of life, diabetes complications and costs, is also needed.

The role of randomized cluster crossover trials for comparative effectiveness testing in anesthesia: design of the Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial.

PubMed

Spence, Jessica; Belley-Côté, Emilie; Lee, Shun Fu; Bangdiwala, Shrikant; Whitlock, Richard; LeManach, Yannick; Syed, Summer; Lamy, Andre; Jacobsohn, Eric; MacIsaac, Sarah; Devereaux, P J; Connolly, Stuart

2018-07-01

Increasingly, clinicians and researchers recognize that studies of interventions need to evaluate not only their therapeutic efficacy (i.e., the effect on an outcome in ideal, controlled settings) but also their real-world effectiveness in broad, unselected patient groups. Effectiveness trials inform clinical practice by comparing variations in therapeutic approaches that fall within the standard of care. In this article, we discuss the need for studies of comparative effectiveness in anesthesia and the limitations of individual patient randomized-controlled trials in determining comparative effectiveness. We introduce the concept of randomized cluster crossover trials as a means of answering questions of comparative effectiveness in anesthesia, using the design of the Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial (Clinicaltrials.gov identifier NCT03053869).

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.

Systematic Review of Plant-Based Homeopathic Basic Research: An Update.

PubMed

Ücker, Annekathrin; Baumgartner, Stephan; Sokol, Anezka; Huber, Roman; Doesburg, Paul; Jäger, Tim

2018-05-01

 Plant-based test systems have been described as a useful tool for investigating possible effects of homeopathic preparations. The last reviews of this research field were published in 2009/2011. Due to recent developments in the field, an update is warranted. Publications on plant-based test systems were analysed with regard to publication quality, reproducibility and potential for further research.  A literature search was conducted in online databases and specific journals, including publications from 2008 to 2017 dealing with plant-based test systems in homeopathic basic research. To be included, they had to contain statistical analysis and fulfil quality criteria according to a pre-defined manuscript information score (MIS). Publications scoring at least 5 points (maximum 10 points) were assumed to be adequate. They were analysed for the use of adequate controls, outcome and reproducibility.  Seventy-four publications on plant-based test systems were found. Thirty-nine publications were either abstracts or proceedings of conferences and were excluded. From the remaining 35 publications, 26 reached a score of 5 or higher in the MIS. Adequate controls were used in 13 of these publications. All of them described specific effects of homeopathic preparations. The publication quality still varied: a substantial number of publications (23%) did not adequately document the methods used. Four reported on replication trials. One replication trial found effects of homeopathic preparations comparable to the original study. Three replication trials failed to confirm the original study but identified possible external influencing factors. Five publications described novel plant-based test systems. Eight trials used systematic negative control experiments to document test system stability.  Regarding research design, future trials should implement adequate controls to identify specific effects of homeopathic preparations and include systematic negative control experiments. Further external and internal replication trials, and control of influencing factors, are needed to verify results. Standardised test systems should be developed. The Faculty of Homeopathy.

Making a decision about trial participation: the feasibility of measuring deliberation during the informed consent process for clinical trials.

PubMed

Gillies, Katie; Elwyn, Glyn; Cook, Jonathan

2014-07-30

Informed consent of trial participants is both an ethical and a legal requirement. When facing a decision about trial participation, potential participants are provided with information about the trial and have the opportunity to have any questions answered before their degree of 'informed-ness' is assessed, usually subjectively, and before they are asked to sign a consent form. Currently, standardised methods for assessing informed consent have tended to be focused on aspects of understanding and associated outcomes, rather than on the process of consent and the steps associated with decision-making. Potential trial participants who were approached regarding participation in one of three randomised controlled trials were asked to complete a short questionnaire to measure their deliberation about trial participation. A total of 136 participants completed the 10-item questionnaire (DelibeRATE) before they made an explicit decision about trial participation (defined as signing the clinical trial consent form). Overall DelibeRATE scores were compared and investigated for differences between trial consenters and refusers. No differences in overall DelibeRATE scores were identified. In addition, there was no significant difference between overall score and the decision to participate, or not, in the parent trial. To our knowledge, this is the first study to prospectively measure the deliberation stage of the informed consent decision-making process of potential trial participants across different conditions and clinical areas. Although there were no differences detected in overall scores or scores of trial consenters and refusers, we did identify some interesting findings. These findings should be taken into consideration by those designing trials and others interested in developing and implementing measures of potential trial participants decision making during the informed consent process for research. International Standard Randomised Controlled Trial Number (ISRCTN) Register ISRCTN60695184 (date of registration: 13 May 2009), ISRCTN80061723 (date of registration: 8 March 2010), ISRCTN69423238 (date of registration: 18 November 2010).

Are placebo-controlled trials of creams for athlete's foot still justified?

PubMed

Crawford, F; Harris, R; Williams, H C

2008-09-01

Placebo-controlled trials are useful in identifying effective treatments where none has existed, but their continued use once efficacy is established arguably contravenes ethical standards for medical research. To consider whether sufficient evidence exists to recommend the abandonment of vehicle-controlled studies in trials of topical treatments for athlete's foot. We searched nine electronic databases and bibliographies of review articles as part of an ongoing Cochrane systematic review from 1966 to 2007. Randomized controlled trials (RCTs) using a vehicle control design involving participants with a mycological diagnosis of a dermatophyte infection of the skin of the foot were included. Allylamines, azoles, ciclopiroxolamine, tolnaftate, butenafine and undecanoates were all more effective than vehicle controls. Evidence of the superiority of azole creams over vehicle controls was fairly consistent from 1975 onwards. Data from patients treated with allylamines have shown their superior effects relative to vehicle controls since 1991 for even short-term outcomes. The superiority of allylamines and azoles over vehicle in vehicle-controlled trials has been well established, and data demonstrating this fact have been available since the completion of early RCTs. These preparations are effective and safe, and investigators of RCTs evaluating topical treatments for athlete's foot need to choose potential comparators as control interventions in the light of this knowledge and to consider the ethics of withholding effective treatment from patients who seek treatment for this common foot infection.

Routine blood cultures in the management of pyelonephritis in pregnancy for improving outcomes.

PubMed

Gomi, Harumi; Goto, Yoshihito; Laopaiboon, Malinee; Usui, Rie; Mori, Rintaro

2015-02-13

Pyelonephritis is a type of urinary tract infection (UTI) that affects the upper urinary tract and kidneys, and is one of the most common conditions for hospitalisation among pregnant women, aside from delivery. Samples of urine and blood are obtained and used for cultures as part of the diagnosis and management of the condition. Acute pyelonephritis requires hospitalisation with intravenous administration of antimicrobial agents. Several studies have questioned the necessity of obtaining blood cultures in addition to urine cultures, citing cost and questioning whether blood testing is superfluous. Pregnant women with bacteraemia require a change in the initial empirical treatment based on the blood culture. However, these cases are not common, and represent approximately 15% to 20% of cases. It is unclear whether blood cultures are essential for the effective management of the condition. To assess the effectiveness of routine blood cultures to improve health outcomes in the management of pyelonephritis in pregnant women. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register without language or date restrictions (31 December 2014). Randomised controlled trials and quasi-randomised trials comparing outcomes among pregnant women with pyelonephritis who received initial management with or without blood cultures. Cluster-randomised trials were eligible for inclusion in this review but none were identified. Clinical trials using a cross-over design were not eligible for inclusion. Two review authors independently assessed one trial report for inclusion. We identified one trial report but this was excluded. No clinical trials met the inclusion criteria for this review. There are no large-scale randomised controlled trials to assess outcomes in the management of pyelonephritis in pregnancy with or without blood cultures. Randomised controlled trials are needed to evaluate the effectiveness of managing pyelonephritis in pregnant women with or without blood cultures, and to assess any adverse outcomes as well as the cost-effectiveness of excluding blood cultures from treatment.

Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials.

PubMed

Cooper, Cindy L; Whitehead, Amy; Pottrill, Edward; Julious, Steven A; Walters, Stephen J

2018-04-01

External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland-Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was -4.4% with limits of agreement of -37.1% to 28.2%. Limits of agreement for randomisation rates were -47.8% to 77.5%. Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate.

Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials

PubMed Central

Whitehead, Amy; Pottrill, Edward; Julious, Steven A; Walters, Stephen J

2018-01-01

Background/aims: External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. Methods: Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland–Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. Results: Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was −4.4% with limits of agreement of −37.1% to 28.2%. Limits of agreement for randomisation rates were −47.8% to 77.5%. Conclusion: Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate. PMID:29361833

Venom immunotherapy for preventing allergic reactions to insect stings.

PubMed

Boyle, Robert J; Elremeli, Mariam; Hockenhull, Juliet; Cherry, Mary Gemma; Bulsara, Max K; Daniels, Michael; Oude Elberink, J N G

2012-10-17

Venom immunotherapy (VIT) is commonly used for preventing further allergic reactions to insect stings in people who have had a sting reaction. The efficacy and safety of this treatment has not previously been assessed by a high-quality systematic review. To assess the effects of immunotherapy using extracted insect venom for preventing further allergic reactions to insect stings in people who have had an allergic reaction to a sting. We searched the following databases up to February 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1806), AMED (from 1985), LILACS (from 1982), the Armed Forces Pest Management Board Literature Retrieval System, and OpenGrey. There were no language or publication status restrictions to our searches. We searched trials databases, abstracts from recent European and North American allergy meetings, and the references of identified review articles in order to identify further relevant trials. Randomised controlled trials of venom immunotherapy using standardised venom extract in insect sting allergy. Two authors independently undertook study selection, data extraction, and assessment of risk of bias. We identified adverse events from included controlled trials and from a separate analysis of observational studies identified as part of a National Institute for Health and Clinical Excellence Health Technology Assessment. We identified 6 randomised controlled trials and 1 quasi-randomised controlled trial for inclusion in the review; the total number of participants was 392. The trials had some risk of bias because five of the trials did not blind outcome assessors to treatment allocation. The interventions included ant, bee, and wasp immunotherapy in children or adults with previous systemic or large local reactions to a sting, using sublingual (one trial) or subcutaneous (six trials) VIT. We found that VIT is effective for preventing systemic allergic reaction to an insect sting, which was our primary outcome measure. This applies whether the sting occurs accidentally or is given intentionally as part of a trial procedure.In the trials, 3/113 (2.7%) participants treated with VIT had a subsequent systemic allergic reaction to a sting, compared with 37/93 (39.8%) untreated participants (risk ratio [RR] 0.10, 95% confidence interval [CI] 0.03 to 0.28). The efficacy of VIT was similar across studies; we were unable to identify a patient group or mode of treatment with different efficacy, although these analyses were limited by small numbers. We were unable to confirm whether VIT prevents fatal reactions to insect stings, because of the rarity of this outcome.Venom immunotherapy was also effective for preventing large local reactions to a sting (5 studies; 112 follow-up stings; RR 0.41, 95% CI 0.24 to 0.69) and for improving quality of life (mean difference [MD] in favour of VIT 1.21 points on a 7-point scale, 95% CI 0.75 to 1.67).We found a significant risk of systemic adverse reaction to VIT treatment: 6 trials reported this outcome, in which 14 of 150 (9.3%) participants treated with VIT and 1 of 135 (0.7%) participants treated with placebo or no treatment suffered a systemic reaction to treatment (RR 8.16, 95% CI 1.53 to 43.46; 2 studies contributed to the effect estimate). Our analysis of 11 observational studies found systemic adverse reactions occurred in 131/921 (14.2%) participants treated with bee venom VIT and 8/289 (2.8%) treated with wasp venom VIT. We found venom immunotherapy using extracted insect venom to be an effective therapy for preventing further allergic reactions to insect stings, which can improve quality of life. The treatment carries a small but significant risk of systemic adverse reaction.

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.

Beyond the Randomized Controlled Trial: A Review of Alternatives in mHealth Clinical Trial Methods

PubMed Central

Wiljer, David; Cafazzo, Joseph A

2016-01-01

Background Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Objective Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. Methods We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Results Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study duration than trials with two data collection points: F4,56=3.2, P=.021, η2=0.18. Single-blinded trials had a longer data collection period compared to open trials: F2,58=3.8, P=.028, η2=0.12. Academic sponsorship was the most common form of trial funding (73%, 52/71). Trials with academic sponsorship had a longer study duration compared to industry sponsorship: F2,61=3.7, P=.030, η2=0.11. Combined, data collection frequency, study masking, sample size, and study sponsorship accounted for 32.6% of the variance in study duration: F4,55=6.6, P<.01, adjusted r2=.33. Only 7 trials had been completed at the time this retrospective review was conducted (10%, 7/71). Conclusions mHealth evaluation methodology has not deviated from common methods, despite the need for more relevant and timely evaluations. There is a need for clinical evaluation to keep pace with the level of innovation of mHealth if it is to have meaningful impact in informing payers, providers, policy makers, and patients. PMID:27613084

Beyond the Randomized Controlled Trial: A Review of Alternatives in mHealth Clinical Trial Methods.

PubMed

Pham, Quynh; Wiljer, David; Cafazzo, Joseph A

2016-09-09

Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study duration than trials with two data collection points: F4,56=3.2, P=.021, η(2)=0.18. Single-blinded trials had a longer data collection period compared to open trials: F2,58=3.8, P=.028, η(2)=0.12. Academic sponsorship was the most common form of trial funding (73%, 52/71). Trials with academic sponsorship had a longer study duration compared to industry sponsorship: F2,61=3.7, P=.030, η(2)=0.11. Combined, data collection frequency, study masking, sample size, and study sponsorship accounted for 32.6% of the variance in study duration: F4,55=6.6, P<.01, adjusted r(2)=.33. Only 7 trials had been completed at the time this retrospective review was conducted (10%, 7/71). mHealth evaluation methodology has not deviated from common methods, despite the need for more relevant and timely evaluations. There is a need for clinical evaluation to keep pace with the level of innovation of mHealth if it is to have meaningful impact in informing payers, providers, policy makers, and patients.

Efficacy and safety of Suanzaoren decoction for primary insomnia: a systematic review of randomized controlled trials

PubMed Central

2013-01-01

Background Insomnia is a widespread human health problem, but there currently are the limitations of conventional therapies available. Suanzaoren decoction (SZRD) is a well known classic Chinese herbal prescription for insomnia and has been treating people’s insomnia for more than thousand years. The objective of this study was to evaluate the efficacy and safety of SZRD for insomnia. Methods A systematic literature search was performed for 6 databases up to July of 2012 to identify randomized control trials (RCTs) involving SZRD for insomniac patients. The methodological quality of RCTs was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions. Results Twelve RCTs with total of 1376 adult participants were identified. The methodological quality of all included trials are no more than 3/8 score. Majority of the RCTs concluded that SZRD was more significantly effective than benzodiazepines for treating insomnia. Despite these positive outcomes, there were many methodological shortcomings in the studies reviewed, including insufficient information about randomization generation and absence of allocation concealment, lack of blinding and no placebo control, absence of intention-to-treat analysis and lack of follow-ups, selective publishing and reporting, and small number of sample sizes. A number of clinical heterogeneity such as diagnosis, intervention, control, and outcome measures were also reviewed. Only 3 trials reported adverse events, whereas the other 9 trials did not provide the safety information. Conclusions Despite the apparent reported positive findings, there is insufficient evidence to support efficacy of SZRD for insomnia due to the poor methodological quality and the small number of trials of the included studies. SZRD seems generally safe, but is insufficient evidence to make conclusions on the safety because fewer studies reported the adverse events. Further large sample-size and well-designed RCTs are needed. PMID:23336848

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.

Pharmacological interventions for self-injurious behaviour in adults with intellectual disabilities: Abridged republication of a Cochrane systematic review.

PubMed

Gormez, A; Rana, F; Varghese, S

2014-07-01

We aimed to determine clinical effectiveness of pharmacological interventions for self-injurious behaviour in adults with intellectual disability. We searched the following databases: CENTRAL; MEDLINE; EMBASE; PsycINFO; CINAHL; SCI; SSCI; Conference Proceedings Citation Index - Science; Conference Proceedings Citation Index - Social Science and Humanities; ZETOC; World Cat .We also searched ClinicalTrials.gov,ICTRP and the reference lists of included trials. We included randomised controlled trials that examined drug interventions versus placebo for self-injurious behaviour. We found five double-blind, placebo-controlled trials, which included a total of 50 people. Four trials compared the effects of naltrexone versus placebo and one trial clomipramine versus placebo. We did not identify any relevant placebo-controlled trials for other drugs. We presented a narrative summary, as meta-analysis was not appropriate due to differences in study designs, differences between interventions and heterogeneous outcome measures. There was weak evidence in included trials that any active drug was more effective than placebo for people with intellectual disability demonstrating self-injurious behaviour. Due to sparse data, an absence of power and statistical significance, and high risk of bias for four of the included trials, we are unable to reach any definite conclusions about the relative benefits of naltrexone or clomipramine compared to placebo. © The Author(s) 2014.

The Effectiveness of Disaster Risk Communication: A Systematic Review of Intervention Studies

PubMed Central

Bradley, Declan T; McFarland, Marie; Clarke, Mike

2014-01-01

Introduction: A disaster is a serious disruption to the functioning of a community that exceeds its capacity to cope within its own resources. Risk communication in disasters aims to prevent and mitigate harm from disasters, prepare the population before a disaster, disseminate information during disasters and aid subsequent recovery. The aim of this systematic review is to identify, appraise and synthesise the findings of studies of the effects of risk communication interventions during four stages of the disaster cycle. Methods: We searched the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, PsycInfo, Sociological Abstracts, Web of Science and grey literature sources for randomised trials, cluster randomised trials, controlled and uncontrolled before and after studies, interrupted time series studies and qualitative studies of any method of disaster risk communication to at-risk populations. Outcome criteria were disaster-related knowledge and behaviour, and health outcomes. Results: Searches yielded 5,224 unique articles, of which 100 were judged to be potentially relevant. Twenty-five studies met the inclusion criteria, and two additional studies were identified from other searching. The studies evaluated interventions in all four stages of the disaster cycle, included a variety of man-made, natural and infectious disease disasters, and were conducted in many disparate settings. Only one randomised trial and one cluster randomised trial were identified, with less robust designs used in the other studies. Several studies reported improvements in disaster-related knowledge and behaviour. Discussion: We identified and appraised intervention studies of disaster risk communication and present an overview of the contemporary literature. Most studies used non-randomised designs that make interpretation challenging. We do not make specific recommendations for practice but highlight the need for high-quality randomised trials and appropriately-analysed cluster randomised trials in the field of disaster risk communication where these can be conducted within an appropriate research ethics framework. PMID:25642365

The national drug abuse treatment clinical trials network data share project: website design, usage, challenges, and future directions.

PubMed

Shmueli-Blumberg, Dikla; Hu, Lian; Allen, Colleen; Frasketi, Michael; Wu, Li-Tzy; Vanveldhuisen, Paul

2013-01-01

There are many benefits of data sharing, including the promotion of new research from effective use of existing data, replication of findings through re-analysis of pooled data files, meta-analysis using individual patient data, and reinforcement of open scientific inquiry. A randomized controlled trial is considered as the 'gold standard' for establishing treatment effectiveness, but clinical trial research is very costly, and sharing data is an opportunity to expand the investment of the clinical trial beyond its original goals at minimal costs. We describe the goals, developments, and usage of the Data Share website (http://www.ctndatashare.org) for the National Drug Abuse Treatment Clinical Trials Network (CTN) in the United States, including lessons learned, limitations, and major revisions, and considerations for future directions to improve data sharing. Data management and programming procedures were conducted to produce uniform and Health Insurance Portability and Accountability Act (HIPAA)-compliant de-identified research data files from the completed trials of the CTN for archiving, managing, and sharing on the Data Share website. Since its inception in 2006 and through October 2012, nearly 1700 downloads from 27 clinical trials have been accessed from the Data Share website, with the use increasing over the years. Individuals from 31 countries have downloaded data from the website, and there have been at least 13 publications derived from analyzing data through the public Data Share website. Minimal control over data requests and usage has resulted in little information and lack of control regarding how the data from the website are used. Lack of uniformity in data elements collected across CTN trials has limited cross-study analyses. The Data Share website offers researchers easy access to de-identified data files with the goal to promote additional research and identify new findings from completed CTN studies. To maximize the utility of the website, ongoing collaborative efforts are needed to standardize the core measures used for data collection in the CTN studies with the goal to increase their comparability and to facilitate the ability to pool data files for cross-study analyses.

Wheeze as an Adverse Event in Pediatric Vaccine and Drug Randomized Controlled Trials: A Systematic Review

PubMed Central

Marangu, Diana; Kovacs, Stephanie; Walson, Judd; Bonhoeffer, Jan; Ortiz, Justin R.; John-Stewart, Grace; Horne, David J.

2016-01-01

Introduction Wheeze is an important sign indicating a potentially severe adverse event in vaccine and drug trials, particularly in children. However, there are currently no consensus definitions of wheeze or associated respiratory compromise in randomized controlled trials (RCTs). Objective To identify definitions and severity grading scales of wheeze as an adverse event in vaccine and drug RCTs enrolling children <5 years and to determine their diagnostic performance based on sensitivity, specificity and inter-observer agreement. Methods We performed a systematic review of electronic databases and reference lists with restrictions for trial settings, English language and publication date ≥ 1970. Wheeze definitions and severity grading were abstracted and ranked by a diagnostic certainty score based on sensitivity, specificity and inter-observer agreement. Results Of 1,205 articles identified using our broad search terms, we identified 58 eligible trials conducted in 38 countries, mainly in high-income settings. Vaccines made up the majority (90%) of interventions, particularly influenza vaccines (65%). Only 15 trials provided explicit definitions of wheeze. Of 24 studies that described severity, 11 described wheeze severity in the context of an explicit wheeze definition. The remaining 13 studies described wheeze severity where wheeze was defined as part of a respiratory illness or a wheeze equivalent. Wheeze descriptions were elicited from caregiver reports (14%), physical examination by a health worker (45%) or a combination (41%). There were 21/58 studies in which wheeze definitions included combined caregiver report and healthcare worker assessment. The use of these two methods appeared to have the highest combined sensitivity and specificity. Conclusion Standardized wheeze definitions and severity grading scales for use in pediatric vaccine or drug trials are lacking. Standardized definitions of wheeze are needed for assessment of possible adverse events as new vaccines and drugs are evaluated. PMID:26319071

Chondroprotection and the prevention of osteoarthritis progression of the knee: a systematic review of treatment agents.

PubMed

Gallagher, Brian; Tjoumakaris, Fotios P; Harwood, Marc I; Good, Robert P; Ciccotti, Michael G; Freedman, Kevin B

2015-03-01

Structure-modifying medications or nutraceuticals may be an effective treatment for osteoarthritis. This study identified 12 treatments that may possess chondroprotective properties: oral glucosamine; chondroitin; nonsteroidal anti-inflammatory drugs (NSAIDs); polyunsaturated fatty acids; S-adenosylmethionine; avocado and soybean unsaponifiable fractions; methylsulfonylmethane; vitamins C, D, and E; intra-articular injections of hyaluronic acid; and platelet-rich plasma (PRP). To perform a systematic review of randomized controlled trials for the effectiveness of each agent in preserving articular cartilage of the knee and delaying the progression of osteoarthritis. Systematic review; Level of evidence, 2. A literature search was performed using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Searches were performed using "treatment," "osteoarthritis," and "knee" as keywords. Selection criteria included randomized controlled trials of ≥12 months, with a placebo control, measuring radiographic changes in joint space width, cartilage volume, or radiographic progression of osteoarthritis. The primary outcome was changes in joint integrity measures. A total of 3514 studies were identified from the initial search, 13 of which met inclusion criteria. Treatment with chondroitin sulfate showed a significant reduction in cartilage loss in 3 of 4 studies identified compared with placebo. Two of 3 trials identified for glucosamine also reported significant structural effects relative to placebo. Intra-articular hyaluronic acid was effective in lowering the rate of cartilage loss in only 1 of 3 studies identified versus placebo. Of the 6 studies identified for NSAIDs, vitamin E, and vitamin D, none showed any structural effect compared with placebo. No studies were found that met the inclusion criteria for polyunsaturated fatty acids, S-adenosylmethionine, avocado and soybean unsaponifiable fractions, methylsulfonylmethane, vitamin C, or PRP. For patients with or at risk for osteoarthritis, the use of glucosamine and chondroitin sulfate may serve as a nonoperative means to protect joint cartilage and delay osteoarthritis progression. Hyaluronic acid injections showed variable efficacy, while NSAIDs and vitamins E and D showed no effect on osteoarthritis progression. The other agents evaluated had no evidence in the literature to support or refute their use for chondroprotection. © 2014 The Author(s).

Osteoporosis therapies: evidence from health-care databases and observational population studies.

PubMed

Silverman, Stuart L

2010-11-01

Osteoporosis is a well-recognized disease with severe consequences if left untreated. Randomized controlled trials are the most rigorous method for determining the efficacy and safety of therapies. Nevertheless, randomized controlled trials underrepresent the real-world patient population and are costly in both time and money. Modern technology has enabled researchers to use information gathered from large health-care or medical-claims databases to assess the practical utilization of available therapies in appropriate patients. Observational database studies lack randomization but, if carefully designed and successfully completed, can provide valuable information that complements results obtained from randomized controlled trials and extends our knowledge to real-world clinical patients. Randomized controlled trials comparing fracture outcomes among osteoporosis therapies are difficult to perform. In this regard, large observational database studies could be useful in identifying clinically important differences among therapeutic options. Database studies can also provide important information with regard to osteoporosis prevalence, health economics, and compliance and persistence with treatment. This article describes the strengths and limitations of both randomized controlled trials and observational database studies, discusses considerations for observational study design, and reviews a wealth of information generated by database studies in the field of osteoporosis.

Maternity leave in normal pregnancy.

PubMed

Leduc, Dean

2011-08-01

To assist maternity care providers in recognizing and discussing health- and illness-related issues in pregnancy and their relationship to maternity benefits. Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in 2009 using appropriate controlled vocabulary (e.g., maternity benefits) and key words (e.g., maternity, benefits, pregnancy). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to December 2009. Grey (unpublished) literature was identified through searching the web sites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.

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.

Enhanced Recovery After Surgery (ERAS®) in Individuals with Diabetes: A Systematic Review.

PubMed

Albalawi, Zaina; Laffin, Michael; Gramlich, Leah; Senior, Peter; McAlister, Finlay A

2017-08-01

Prevalence of diabetes in surgical patients is 10-40%. It is well recognized that they have higher rates of complications, and longer stays in hospital compared to patients without diabetes. Enhanced recovery after surgery (ERAS) is an evidence-based multimodal surgical care pathway that improves postoperative complications and length of stay in patients without diabetes. This review evaluates the evidence on whether individuals with diabetes would benefit from ERAS implementation. MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE searched with no language restrictions applied. Conference proceedings and bibliographies were reviewed. Experts in the field were contacted, and www.clinicaltrials.gov searched for ongoing trials. Randomized controlled trials (RCT) looking at individuals with diabetes undergoing surgery randomized to ERAS ® or conventional care. Non-randomized controlled trials, controlled before-after studies, interrupted time series, and cohort studies with concurrent controls were also considered. Two authors independently screened studies. The electronic search yielded 437 references. After removing duplicates, 376 were screened for eligibility. Conference proceedings and bibliographies identified additional references. Searching www.clinicaltrials.gov yielded 59 references. Contacting experts in the field identified no further studies. Fourteen full articles were assessed and subsequently excluded for the following reasons: used an intervention other than ERAS ® , did not include patients with diabetes, or used an uncontrolled observational design. To date, the effects of ERAS ® on patients with diabetes have not been rigorously evaluated. This review highlights the lack of evidence in this area and provides guidance on design for future studies.

Allergy-immunology practice parameters and strength of recommendation data: an evolutionary perspective.

PubMed

Park, Matthew H; Banks, Taylor A; Nelson, Michael R

2016-03-01

The practice parameters for allergy and immunology (A/I) are a valuable tool guiding practitioners' clinical practice. The A/I practice parameters have evolved over time in the context of evidence-based medicine milestones. To identify evolutionary trends in the character, scope, and evidence underlying recommendations in the A/I practice parameters. Practice parameters that have guided A/I from 1995 through 2014 were analyzed. Statements and recommendations with strength of recommendation categories A and B were considered to have a basis in evidence from controlled trials. Forty-three publications and updates covering 25 unique topics were identified. There was great variability in the number of recommendations made and the proportion of statements with controlled trial evidence. The mean number of recommendations made per practice parameter has decreased significantly, from 95.8 to a mean of 38.3. There also is a trend toward an increased proportion of recommendations based on controlled trial evidence in practice parameters with fewer recommendations, with a mean of 30.7% in practice parameters with at least 100 recommendations based on controlled trial evidence compared with 48.3% in practice parameters with 30 to 100 recommendations and 51.0% in those with fewer than 30 recommendations. The A/I practice parameters have evolved significantly over time. Encouragingly, greater controlled trial evidence is associated with updated practice parameters and a recent trend of more narrowly focused topics. These findings should only bolster and inspire confidence in the utility of the A/I practice parameters in assisting practitioners to navigate through the uncertainty that is intrinsic to medicine in making informed decisions with patients. Published by Elsevier Inc.

Does Ureaplasma spp. cause chronic lung disease of prematurity: Ask the audience?

PubMed Central

Maxwell, Nicola C.; Nuttall, Diane; Kotecha, Sailesh

2009-01-01

Ureaplasma has long been implicated in the pathogenesis of both preterm labour and neonatal morbidity, particularly chronic lung disease of prematurity (CLD), but despite numerous studies, reviews and meta-analyses, its exact role remains unclear. Many papers call for a definitive randomised control trial to determine if eradication of pulmonary Ureaplasma decreases the rates of CLD but few address in detail the obstacles to an adequately powered clinical trial. We review the evidence for Ureaplasma as a causative agent in CLD, asking why a randomised control trial has not been performed. We surveyed the opinions of senior neonatologists in the UK on whether they felt that there was sufficient evidence for Ureaplasma either causing or not causing CLD and whether a definitive trial was needed, as well as their views on the design of such a trial. Additionally, we ascertained current practice with respect to Ureaplasma detection in preterm neonates in the UK. There is clear support for an adequately powered randomised controlled clinical trial by senior neonatologists in the UK. There are no reasons why a definitive trial cannot be conducted especially as the appropriate samples, and methods to culture or identify the organism by PCR are already available. PMID:19144476

Evidence for compliance with long-term medication: a systematic review of randomised controlled trials.

PubMed

King, Michelle A; Pryce, Rebecca L

2014-02-01

Pharmacists play a pivotal role in optimising medication use which often includes actions to maximise compliance with long-term medication. The best evidence to support medication use is derived from randomised controlled trials (RCTs). It is often assumed that 100 % compliance is required to obtain the outcomes identified in the trial. This assumption needs to be examined. To systematically review the reporting of compliance in RCTs of long-term medications. RCTs published in the New England Journal of Medicine, Journal of the American Medical Association, Lancet and BMJ in 2012, were reviewed to identify trials of medications for long-term use in adults. These trials were examined to evaluate the reporting of compliance. The proportion of trials reporting compliance data, the methods used, and the proportion of trials using more than one method to determine compliance. Of the 289 RCTs published in 2012, 25 assessed long-term medications in adults. Compliance was reported in 12 (48 %) studies and only 2 (8 %) studies used more than one method to measure compliance. Pill count was the most commonly reported method for measuring compliance, with patient reports and blood levels also being used. The reporting of compliance in RCTs is poor and the methodology inconsistent. The methods used overestimate compliance. If compliance in a clinical trial is low, the evidence for the effectiveness and most importantly safety of the medication(s) is questionable. Two or more methods, one of which is standardised, should be used to measure compliance in clinical trials. The requirement to report compliance should be included in publication guidelines.

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.

Predictors of physical activity at 12 month follow-up after a supervised exercise intervention in postmenopausal women.

PubMed

Aparicio-Ting, Fabiola E; Farris, Megan; Courneya, Kerry S; Schiller, Ashley; Friedenreich, Christine M

2015-05-05

Few studies have examined recreational physical activity (RPA) after participating in a structured exercise intervention. More specifically, little is known about the long-term effects of exercise interventions in post-menopausal women. This study had two objectives: 1) To compare RPA in postmenopausal women in the exercise group and the control group 12 months after the end of the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial; and 2) To apply the Theory of Planned Behaviour (TPB) to identify predictors of RPA 12 months post-intervention among women in the exercise group. Self-reported RPA 12-months post-intervention from a validated questionnaire was used to estimate RPA levels for control group (118/160, 74% response) and exercise group participants (126/160, 79% response). Bivariate analysis was used to compare RPA between exercise and control group participants and to identify TPB variables for multivariate analysis. Logistic regression was applied to TPB data collected from self- administered questionnaires at end of trial by exercise group participants (126/160, 79% response) to identify predictors of long-term RPA. At 12 months post-intervention, 62% of women in the exercise group were active compared to 58% of controls (p = 0.52). Of the TPB constructs examined, self-efficacy (OR =2.98 (1.08-8.20)) and behavioural beliefs (OR = 1.46 (1.03-2.06)) were identified as predictors of RPA for exercise group participants. Levels of RPA in the exercise and control groups were comparable 12 months post intervention, indicating that participation in the ALPHA trial was associated with increased physical activity in previously inactive women, regardless of randomization into either the exercise group or in the control group. Exercise interventions that promote self-efficacy and positive behavioural beliefs have the potential to have long-term impacts on physical activity behaviour, although further research is needed to examine additional psychological, social and environmental predictors of long-term RPA in post-menopausal women. ClinicalTrials.gov NCT00522262.

Smartphone app design for the wireless control of a neuromuscular electrical stimulator device with integrated randomization allocation process for RCT applications.

PubMed

Sweeney, Dean; Quinlan, Leo R; OLaighin, Gearoid

2015-08-01

The use of NMES has evolved over the last five decades. Technological advancements have transformed these once complex systems into user-friendly devices with enhanced control functions, leading to new applications of NMES being investigated. The use of Randomized Control Trial (RCT) methodology in evaluating the effectiveness of new and existing applications of NMES is a demanding process adding time and cost to a translation into clinical practice. Poor quality trials may result in poor evidence of NMES effectiveness. In this paper some of the key challenges encountered in NMES clinical trials are identified with the aim of purposing a solution to address these challenges through the adoption of Smartphone technology. The design and evaluation of a smartphone application to provide automatic blind randomization control and facilitating the wireless temporal control of a portable Bluetooth enabled NMES is presented.

Novel ways to explore surgical interventions in randomised controlled trials: applying case study methodology in the operating theatre.

PubMed

Blencowe, Natalie S; Blazeby, Jane M; Donovan, Jenny L; Mills, Nicola

2015-12-28

Multi-centre randomised controlled trials (RCTs) in surgery are challenging. It is particularly difficult to establish standards of surgery and ensure that interventions are delivered as intended. This study developed and tested methods for identifying the key components of surgical interventions and standardising interventions within RCTs. Qualitative case studies of surgical interventions were undertaken within the internal pilot phase of a surgical RCT for obesity (the By-Band study). Each case study involved video data capture and non-participant observation of gastric bypass surgery in the operating theatre and interviews with surgeons. Methods were developed to transcribe and synchronise data from video recordings with observational data to identify key intervention components, which were then explored in the interviews with surgeons. Eight qualitative case studies were undertaken. A novel combination of video data capture, observation and interview data identified variations in intervention delivery between surgeons and centres. Although surgeons agreed that the most critical intervention component was the size and shape of the gastric pouch, there was no consensus regarding other aspects of the procedure. They conceded that evidence about the 'best way' to perform bypass was lacking and, combined with the pragmatic nature of the By-Band study, agreed that strict standardisation of bypass might not be required. This study has developed and tested methods for understanding how surgical interventions are designed and delivered delivered in RCTs. Applying these methods more widely may help identify key components of interventions to be delivered by surgeons in trials, enabling monitoring of key components and adherence to the protocol. These methods are now being tested in the context of other surgical RCTs. Current Controlled Trials ISRCTN00786323 , 05/09/2011.

The Misconception of Case-Control Studies in the Plastic Surgery Literature: A Literature Audit.

PubMed

Hatchell, Alexandra C; Farrokhyar, Forough; Choi, Matthew

2017-06-01

Case-control study designs are commonly used. However, many published case-control studies are not true case-controls and are in fact mislabeled. The purpose of this study was to identify all case-control studies published in the top three plastic surgery journals over the past 10 years, assess which were truly case-control studies, clarify the actual design of the articles, and address common misconceptions. MEDLINE, Embase, and Web of Science databases were searched for case-control studies in the three highest-impact factor plastic surgery journals (2005 to 2015). Two independent reviewers screened the resulting titles, abstracts, and methods, if applicable, to identify articles labeled as case-control studies. These articles were appraised and classified as true case-control studies or non-case-control studies. The authors found 28 articles labeled as case-control studies. However, only six of these articles (21 percent) were truly case-control designs. Of the 22 incorrectly labeled studies, one (5 percent) was a randomized controlled trial, three (14 percent) were nonrandomized trials, two (9 percent) were prospective comparative cohort designs, 14 (64 percent) were retrospective comparative cohort designs, and two (9 percent) were cross-sectional designs. The mislabeling was worse in recent years, despite increases in evidence-based medicine awareness. The majority of published case-control studies are not in fact case-control studies. This misunderstanding is worsening with time. Most of these studies are actually comparative cohort designs. However, some studies are truly clinical trials and thus a higher level of evidence than originally proposed.

Intensive gestational glycemic management and childhood obesity: a systematic review and meta-analysis.

PubMed

Guillemette, L; Durksen, A; Rabbani, R; Zarychanski, R; Abou-Setta, A M; Duhamel, T A; McGavock, J M; Wicklow, B

2017-07-01

Hyperglycemia in pregnancy is associated with increased risk of offspring childhood obesity. Treatment reduces macrosomia; however, it is unclear if this effect translates into a reduced risk of childhood obesity. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy and safety of intensive glycemic management in pregnancy in preventing childhood obesity. We searched MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov up to February 2016 and conference abstracts from 2010 to 2015. Two reviewers independently identified randomized controlled trials evaluating intensive glycemic management interventions for hyperglycemia in pregnancy and included four of the 383 citations initially identified. Two reviewers independently extracted study data and evaluated internal validity of the studies using the Cochrane Collaboration's Risk of Bias tool. Data were pooled using random-effects models. Statistical heterogeneity was quantified using the I 2 test. The primary outcome was age- and sex-adjusted childhood obesity. Secondary outcomes included childhood weight and waist circumference and maternal hypoglycemia during the trial (safety outcome). The four eligible trials (n=767 children) similarly used lifestyle and insulin to manage gestational hyperglycemia, but only two measured offspring obesity and waist circumference and could be pooled for these outcomes. We found no association between intensive gestational glucose management and childhood obesity at 7-10 years of age (relative risk 0.89, 95% confidence interval (CI) 0.65 to 1.22; two trials; n=568 children). Waist circumference also did not differ between treatment and control arms (mean difference, -2.68 cm; 95% CI, -8.17 to 2.81 cm; two trials; n=568 children). Intensive gestational glycemic management is not associated with reduced childhood obesity in offspring, but randomized data is scarce. Long-term follow-up of trials should be prioritized and comprehensive measures of childhood metabolic risk should be considered as outcomes in future trials.

CONSORT in China: past development and future direction.

PubMed

Song, Tian-Jiao; Leng, Hou-Fu; Zhong, Linda Ld; Wu, Tai-Xiang; Bian, Zhao-Xiang

2015-06-01

The Consolidated Standards of Reporting Trials (CONSORT) Statement was published in 1996, and first introduced to China in 2001. Although CONSORT has been widely accepted in high-quality international journals, we still need to have more investigation on how many Chinese journals have adopted the CONSORT Statement, and whether the quality of reporting has improved. A systematic search of the "Instructions to authors" in all Chinese medical journals in China Academic Journals (CAJ) Full-text Database was conducted up to February 2012 and only 7 journals officially listed the requirements of the CONSORT Statement. The research articles about randomized controlled trials (RCTs) published in 2002, 2004, 2006, 2008, and 2010 from journals which had specifically adopted the CONSORT Statement, and from 30 top journals based on the Chinese Science Citation Index (CSCI) 2011 as the control group, were identified. The quality of both cohorts of articles was assessed using the revised CONSORT Checklist and Jadad scale. A total of 1221 Chinese medical journals was identified. Only seven journals stated clearly in the "Instructions to authors" that authors should adopt the CONSORT requirement in the clinical trial paper. None of these journals is among the control group in the CSCI 2011. In the selected years, a total of 171 articles from 7 journals which had adopted CONSORT and 232 articles in the control were identified as including RCT trials. The average scores according to the revised CONSORT Checklist were 29.47 for the CONSORT-adopting journals and 25.57 for the control group; while the average scores based on the Jadad scale were 2.53 for CONSORT-adopting journals and 1.97 for the control group. Few journals among Chinese medical journals have adopted the CONSORT Statement. The overall quality of RCT reports in the 7 journals which have adopted CONSORT was better than those in the top 30 journals which have not adopted CONSORT. The quality of RCT reports in Chinese journals needs further improvement, and the CONSORT Statement could be a very helpful guideline.

Identifying Items to Assess Methodological Quality in Physical Therapy Trials: A Factor Analysis

PubMed Central

Cummings, Greta G.; Fuentes, Jorge; Saltaji, Humam; Ha, Christine; Chisholm, Annabritt; Pasichnyk, Dion; Rogers, Todd

2014-01-01

Background Numerous tools and individual items have been proposed to assess the methodological quality of randomized controlled trials (RCTs). The frequency of use of these items varies according to health area, which suggests a lack of agreement regarding their relevance to trial quality or risk of bias. Objective The objectives of this study were: (1) to identify the underlying component structure of items and (2) to determine relevant items to evaluate the quality and risk of bias of trials in physical therapy by using an exploratory factor analysis (EFA). Design A methodological research design was used, and an EFA was performed. Methods Randomized controlled trials used for this study were randomly selected from searches of the Cochrane Database of Systematic Reviews. Two reviewers used 45 items gathered from 7 different quality tools to assess the methodological quality of the RCTs. An exploratory factor analysis was conducted using the principal axis factoring (PAF) method followed by varimax rotation. Results Principal axis factoring identified 34 items loaded on 9 common factors: (1) selection bias; (2) performance and detection bias; (3) eligibility, intervention details, and description of outcome measures; (4) psychometric properties of the main outcome; (5) contamination and adherence to treatment; (6) attrition bias; (7) data analysis; (8) sample size; and (9) control and placebo adequacy. Limitation Because of the exploratory nature of the results, a confirmatory factor analysis is needed to validate this model. Conclusions To the authors' knowledge, this is the first factor analysis to explore the underlying component items used to evaluate the methodological quality or risk of bias of RCTs in physical therapy. The items and factors represent a starting point for evaluating the methodological quality and risk of bias in physical therapy trials. Empirical evidence of the association among these items with treatment effects and a confirmatory factor analysis of these results are needed to validate these items. PMID:24786942

Identifying items to assess methodological quality in physical therapy trials: a factor analysis.

PubMed

Armijo-Olivo, Susan; Cummings, Greta G; Fuentes, Jorge; Saltaji, Humam; Ha, Christine; Chisholm, Annabritt; Pasichnyk, Dion; Rogers, Todd

2014-09-01

Numerous tools and individual items have been proposed to assess the methodological quality of randomized controlled trials (RCTs). The frequency of use of these items varies according to health area, which suggests a lack of agreement regarding their relevance to trial quality or risk of bias. The objectives of this study were: (1) to identify the underlying component structure of items and (2) to determine relevant items to evaluate the quality and risk of bias of trials in physical therapy by using an exploratory factor analysis (EFA). A methodological research design was used, and an EFA was performed. Randomized controlled trials used for this study were randomly selected from searches of the Cochrane Database of Systematic Reviews. Two reviewers used 45 items gathered from 7 different quality tools to assess the methodological quality of the RCTs. An exploratory factor analysis was conducted using the principal axis factoring (PAF) method followed by varimax rotation. Principal axis factoring identified 34 items loaded on 9 common factors: (1) selection bias; (2) performance and detection bias; (3) eligibility, intervention details, and description of outcome measures; (4) psychometric properties of the main outcome; (5) contamination and adherence to treatment; (6) attrition bias; (7) data analysis; (8) sample size; and (9) control and placebo adequacy. Because of the exploratory nature of the results, a confirmatory factor analysis is needed to validate this model. To the authors' knowledge, this is the first factor analysis to explore the underlying component items used to evaluate the methodological quality or risk of bias of RCTs in physical therapy. The items and factors represent a starting point for evaluating the methodological quality and risk of bias in physical therapy trials. Empirical evidence of the association among these items with treatment effects and a confirmatory factor analysis of these results are needed to validate these items. © 2014 American Physical Therapy Association.

A systematic review of randomized controlled trials of interventions designed to decrease child abuse in high-risk families.

PubMed

Levey, Elizabeth J; Gelaye, Bizu; Bain, Paul; Rondon, Marta B; Borba, Christina P C; Henderson, David C; Williams, Michelle A

2017-03-01

Child abuse is a global problem, and parents with histories of childhood abuse are at increased risk of abusing their offspring. The objective of this systematic review is to provide a clear overview of the existing literature of randomized controlled trials evaluating the effectiveness of interventions to prevent child abuse. PubMed, PsychINFO, Web of Science, Sociological Abstracts, and CINAHL were systematically searched and expanded by hand search. This review includes all randomized controlled trials (RCTs) of interventions designed to prevent abuse among mothers identified as high-risk. Of the eight studies identified, only three found statistically significant reductions in abuse by any measure, and only two found reductions in incidents reported to child protective services. While much has been written about child abuse in high-risk families, few RCTs have been performed. Only home visitation has a significant evidence base for reducing child abuse, and the findings vary considerably. Also, data from low- and middle-income countries are limited. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effects of yoga exercises for headaches: a systematic review of randomized controlled trials

PubMed Central

Kim, Sang-Dol

2015-01-01

[Purpose] To assess the evidence for the effectiveness of yoga exercises in the management of headaches. [Subjects and Methods] A search was conducted of six electronic databases to identify randomized controlled trials (RCTs) reporting the effects of yogic intervention on headaches published in any language before January 2015. Quality assessment was conducted using the Cochrane risk of bias tool. [Results] One potential trial was identified and included in this review. The quality critical appraisal indicated a moderate risk of bias. The available data could only be included as a narrative description. Headache intensity and frequency, anxiety and depression scores, and symptomatic medication use were significantly lower in the yoga group compared to the control group. [Conclusion] There is evidence from one RCT that yoga exercises may be beneficial for headaches. However, the findings should be interpreted with caution due to the small number of RCTs. Therefore, further rigorous methodological and high quality RCTs are required to investigate the hypothesis that yoga exercises alleviate headaches, and to confirm and further comprehend the effects of standardized yoga programs on headaches. PMID:26311986

Participant recruitment into a randomised controlled trial of exercise therapy for people with multiple sclerosis.

PubMed

Carter, Anouska; Humphreys, Liam; Snowdon, Nicky; Sharrack, Basil; Daley, Amanda; Petty, Jane; Woodroofe, Nicola; Saxton, John

2015-10-15

The success of a clinical trial is often dependant on whether recruitment targets can be met in the required time frame. Despite an increase in research into the benefits of exercise in people with multiple sclerosis (PwMS), no trial has reported detailed data on effective recruitment strategies for large-scale randomised controlled trials. The main purpose of this report is to provide a detailed outline of recruitment strategies, rates and estimated costs in the Exercise Intervention for Multiple Sclerosis (ExIMS) trial to identify best practices for future trials involving multiple sclerosis (MS) patient recruitment. The ExIMS researchers recruited 120 PwMS to participate in a 12-week exercise intervention. Participants were randomly allocated to either exercise or usual-care control groups. Participants were sedentary, aged 18-65 years and had Expanded Disability Status Scale scores of 1.0-6.5. Recruitment strategies included attendance at MS outpatient clinics, consultant mail-out and trial awareness-raising activities. A total of 120 participants were recruited over the course of 34 months. To achieve this target, 369 potentially eligible and interested participants were identified. A total of 60 % of participants were recruited via MS clinics, 29.2 % from consultant mail-outs and 10.8 % through trial awareness. The randomisation yields were 33.2 %, 31.0 % and 68.4 % for MS clinic, consultant mail-outs and trial awareness strategies, respectively. The main reason for ineligibility was being too active (69.2 %), whilst for eligible participants the most common reason for non-participation was the need to travel to the study site (15.8 %). Recruitment via consultant mail-out was the most cost-effective strategy, with MS clinics being the most time-consuming and most costly. To reach recruitment targets in a timely fashion, a variety of methods were employed. Although consultant mail-outs were the most cost-effective recruitment strategy, use of this method alone would not have allowed us to obtain the predetermined number of participants in the required time period, thus leading to costly extensions of the project or failure to reach the number of participants required for sufficient statistical power. Thus, a multifaceted approach to recruitment is recommended for future trials. International Standard Randomised Controlled Trial Registry number: ISRCTN41541516 ; date registered: 5 February 2009.

A Scoping Review of Economic Evaluations Alongside Randomised Controlled Trials of Home Monitoring in Chronic Disease Management.

PubMed

Kidholm, Kristian; Kristensen, Mie Borch Dahl

2018-04-01

Many countries have considered telemedicine and home monitoring of patients as a solution to the demographic challenges that health-care systems face. However, reviews of economic evaluations of telemedicine have identified methodological problems in many studies as they do not comply with guidelines. The aim of this study was to examine economic evaluations alongside randomised controlled trials of home monitoring in chronic disease management and hereby to explore the resources included in the programme costs, the types of health-care utilisation that change as a result of home monitoring and discuss the value of economic evaluation alongside randomised controlled trials of home monitoring on the basis of the studies identified. A scoping review of economic evaluations of home monitoring of patients with chronic disease based on randomised controlled trials and including information on the programme costs and the costs of equipment was carried out based on a Medline (PubMed) search. Nine studies met the inclusion criteria. All studies include both costs of equipment and use of staff, but there is large variation in the types of equipment and types of tasks for the staff included in the costs. Equipment costs constituted 16-73% of the total programme costs. In six of the nine studies, home monitoring resulted in a reduction in primary care or emergency contacts. However, in total, home monitoring resulted in increased average costs per patient in six studies and reduced costs in three of the nine studies. The review is limited by the small number of studies found and the restriction to randomised controlled trials, which can be problematic in this area due to lack of blinding of patients and healthcare professionals and the difficulty of implementing organisational changes in hospital departments for the limited period of a trial. Furthermore, our results may be based on assessments of older telemedicine interventions.

Comparison of reporting phase III randomized controlled trials of antibiotic treatment for common bacterial infections in ClinicalTrials.gov and matched publications.

PubMed

Shepshelovich, D; Yelin, D; Gafter-Gvili, A; Goldman, S; Avni, T; Yahav, D

2018-02-15

Discrepancies between ClinicalTrials.gov entries and matching publications were previously described in general medicine. We aimed to evaluate the consistency of reporting in trials addressing systemic antibiotic therapy. We searched ClinicalTrials.gov for completed phase III trials comparing antibiotic regimens until May 2017. Matched publications were identified in PubMed. Two independent reviewers extracted data and identified inconsistencies. Reporting was assessed among studies started before and after 1 July 2005, when the International Committee of Medical Journal Editors (ICMJE) required mandatory registration as a prerequisite for considering a trial for publication. Matching publications were identified for 75 (70%) of 107 ClinicalTrials.gov entries. Median time from study completion to publication was 26 months (interquartile range 19-42). Primary outcome definition was inconsistent between ClinicalTrials.gov and publications in seven trials (7/72, 10%) and reporting of the primary outcome timeframe was inconsistent in 14 (14/71, 20%). Secondary outcomes definitions were inconsistent in 36 trials (36/66, 55%). Reporting of inclusion criteria and study timeline were inconsistent in 17% (13/65) and 3% (2/65), respectively. Trials started after July 2005 were significantly less likely to have reporting inconsistencies and were published in higher impact factor journals. We found a lower inconsistency rate of outcome reporting compared with other medical disciplines. Reporting completeness and consistency were significantly better after July 2005. The ICMJE requirement for mandatory registration was associated with significant improvement in reporting quality in infectious diseases trials. Prolonged time lag to publication and missing data from unpublished trials should raise a discussion on current reporting and publishing procedures. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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.

Individual psychological therapy in the outpatient treatment of adults with anorexia nervosa.

PubMed

Hay, Phillipa J; Claudino, Angélica M; Touyz, Stephen; Abd Elbaky, Ghada

2015-07-27

Anorexia nervosa is a disorder with high morbidity and significant mortality. It is most common in young adult women, in whom the incidence may be increasing. The focus of treatment has moved to an outpatient setting, and a number of differing psychological therapies are presently used in treatment. This is an update of a Cochrane review which was last published in 2008. To assess the effects of specific individual psychological therapies for anorexia nervosa in adults or older adolescents treated in an outpatient setting. We searched the Cochrane Depression, Anxiety and Neurosis Review Group Specialised Register (CCDANCTR) (16 July 2014). This register includes relevant randomised controlled trials from: the Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). We screened reference lists of all included studies and sent letters to identified, notable researchers requesting information on unpublished or ongoing studies. All randomised controlled trials of one or more individual outpatient psychological therapies for adults with anorexia nervosa, as defined by DSM-5 or similar international criteria. We selected a range of outcome variables, including physical state, severity of eating disorder attitudes and beliefs, interpersonal function, and general psychiatric symptom severity. Continuous outcome data comparisons used the mean or standardised mean difference (MD or SMD), and binary outcome comparisons used the risk ratio (RR). Two review authors (PH and AC or ST) extracted data independently. We identified 10 trials from the search, with a total of 599 anorexia nervosa participants, and included them in the review. Seven had been identified in the previous versions of this review and we now include three new trials. We now deem one previously identified ongoing trial to be ineligible, and six ongoing trials are new for this update. Two of the 10 trials included children. Trials tested diverse psychological therapies and comparability was poor. Risks of bias were mostly evident through lack of blinded outcome assessments (in 60% of studies) and incomplete data reporting (attrition bias).The results suggest that treatment as usual (TAU) when delivered by a non-eating-disorder specialist or similar may be less efficacious than focal psychodynamic therapy. This was suggested for a primary outcome of recovery by achievement of a good or intermediate outcome on the Morgan and Russell Scale (RR 0.70, 95% confidence interval (CI) 0.51 to 0.97; 1 RCT, 40 participants; very low-quality evidence). However there were no differences between cognitive analytic therapy and TAU for this outcome (RR 0.78, 95% CI 0.61 to 1.00; 2 RCTs, 71 participants; very low-quality evidence), nor for body mass index (BMI). There were no differences in overall dropout rates between individual psychological therapies and TAU.Two trials found a non-specific specialist therapy (Specialist Supportive Clinical Management) or an Optimised TAU delivered by therapists with eating disorder expertise was similar in outcomes to cognitive behaviour therapy (BMI MD -0.00, 95% CI -0.91 to 0.91; 197 participants, low-quality evidence). When comparing individual psychological therapies with each other, no specific treatment was consistently superior to any other specific approach. Dietary advice as a control arm had a 100% non-completion rate in one trial (35 participants). None of the trials identified any adverse effects. Insufficient power was problematic for the majority of trials. There was a suggestion in one trial that focal psychodynamic therapy might be superior to TAU, but this is in the context of TAU performing poorly. An alternative control condition of dietary advice alone appeared to be unacceptable, but again this is based on just one trial. Owing to the risk of bias and limitations of studies, notably small sample sizes, we can draw no specific conclusions about the effects of specific individual psychological therapies for anorexia nervosa in adults or older adolescents. Larger RCTs of longer treatment duration and follow-up are needed.

Development of a framework to improve the process of recruitment to randomised controlled trials (RCTs): the SEAR (Screened, Eligible, Approached, Randomised) framework.

PubMed

Wilson, Caroline; Rooshenas, Leila; Paramasivan, Sangeetha; Elliott, Daisy; Jepson, Marcus; Strong, Sean; Birtle, Alison; Beard, David J; Halliday, Alison; Hamdy, Freddie C; Lewis, Rebecca; Metcalfe, Chris; Rogers, Chris A; Stein, Robert C; Blazeby, Jane M; Donovan, Jenny L

2018-01-19

Research has shown that recruitment to trials is a process that stretches from identifying potentially eligible patients, through eligibility assessment, to obtaining informed consent. The length and complexity of this pathway means that many patients do not have the opportunity to consider participation. This article presents the development of a simple framework to document, understand and improve the process of trial recruitment. Eight RCTs integrated a QuinteT Recruitment Intervention (QRI) into the main trial, feasibility or pilot study. Part of the QRI required mapping the patient recruitment pathway using trial-specific screening and recruitment logs. A content analysis compared the logs to identify aspects of the recruitment pathway and process that were useful in monitoring and improving recruitment. Findings were synthesised to develop an optimised simple framework that can be used in a wide range of RCTs. The eight trials recorded basic information about patients screened for trial participation and randomisation outcome. Three trials systematically recorded reasons why an individual was not enrolled in the trial, and further details why they were not eligible or approached, or declined randomisation. A framework to facilitate clearer recording of the recruitment process and reasons for non-participation was developed: SEAR - Screening, to identify potentially eligible trial participants; Eligibility, assessed against the trial protocol inclusion/exclusion criteria; Approach, the provision of oral and written information and invitation to participate in the trial, and Randomised or not, with the outcome of randomisation or treatment received. The SEAR framework encourages the collection of information to identify recruitment obstacles and facilitate improvements to the recruitment process. SEAR can be adapted to monitor recruitment to most RCTs, but is likely to add most value in trials where recruitment problems are anticipated or evident. Further work to test it more widely is recommended.

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.

Omitted data in randomized controlled trials for anxiety and depression: A systematic review of the inclusion of sexual orientation and gender identity.

PubMed

Heck, Nicholas C; Mirabito, Lucas A; LeMaire, Kelly; Livingston, Nicholas A; Flentje, Annesa

2017-01-01

The current study examined the frequency with which randomized controlled trials (RCTs) of behavioral and psychological interventions for anxiety and depression include data pertaining to participant sexual orientation and nonbinary gender identities. Using systematic review methodology, the databases PubMed and PsycINFO were searched to identify RCTs published in 2004, 2009, and 2014. Random selections of 400 articles per database per year (2,400 articles in total) were considered for inclusion in the review. Articles meeting inclusion criteria were read and coded by the research team to identify whether the trial reported data pertaining to participant sexual orientation and nonbinary gender identities. Additional trial characteristics were also identified and indexed in our database (e.g., sample size, funding source). Of the 232 articles meeting inclusion criteria, only 1 reported participants' sexual orientation, and zero articles included nonbinary gender identities. A total of 52,769 participants were represented in the trials, 93 of which were conducted in the United States, and 43 acknowledged the National Institutes of Health as a source of funding. Despite known mental health disparities on the basis of sexual orientation and nonbinary gender identification, researchers evaluating interventions for anxiety and depression are not reporting on these important demographic characteristics. Reporting practices must change to ensure that our interventions generalize to lesbian, gay, bisexual, and transgender persons. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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.

Reporting of symptoms in randomized controlled trials of atopic eczema treatments: a systematic review.

PubMed

Gerbens, L A A; Chalmers, J R; Rogers, N K; Nankervis, H; Spuls, P I

2016-10-01

'Symptoms' is a core outcome domain for atopic eczema (AE) trials, agreed by consensus as part of the Harmonising Outcome Measures for Eczema (HOME) initiative. To standardize and validate the core domain symptoms and symptom instruments for AE trials the HOME roadmap is followed. Its first step is to establish if and how symptoms have been measured in published AE treatment trials. Therefore the Global Resource for Eczema Trials database was used to collect all randomized controlled trials (RCTs) of treatments for AE between January 2000 and April 2014. Study selection and data extraction were performed by three reviewers independently. We identified the use of symptoms in 295 of 378 trials (78%). Symptoms as a primary end point were applied by 147 RCTs (50%). Seventeen different symptoms were measured, but mostly itch and sleep loss. Symptoms were assessed by only 37% of trials by a stand-alone symptom measurement. Overall 63% of RCTs used a composite instrument, and 30 different instruments were identified. The Scoring Atopic Dermatitis (SCORAD) index was the most commonly applied, but only 23% of RCTs reported the SCORAD symptom score separately. This systematic review demonstrates that symptoms, most frequently itch and sleep loss, are commonly reported in AE treatment trials, but are measured using many different instruments. Often symptoms are evaluated as part of a composite instrument, and currently it is not possible to extract symptoms-only data from most published studies. Future trials should report symptom scores to permit meta-analysis of the core outcomes. © 2016 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Reporting of Positive Results in Randomized Controlled Trials of Mindfulness-Based Mental Health Interventions.

PubMed

Coronado-Montoya, Stephanie; Levis, Alexander W; Kwakkenbos, Linda; Steele, Russell J; Turner, Erick H; Thombs, Brett D

2016-01-01

A large proportion of mindfulness-based therapy trials report statistically significant results, even in the context of very low statistical power. The objective of the present study was to characterize the reporting of "positive" results in randomized controlled trials of mindfulness-based therapy. We also assessed mindfulness-based therapy trial registrations for indications of possible reporting bias and reviewed recent systematic reviews and meta-analyses to determine whether reporting biases were identified. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS databases were searched for randomized controlled trials of mindfulness-based therapy. The number of positive trials was described and compared to the number that might be expected if mindfulness-based therapy were similarly effective compared to individual therapy for depression. Trial registries were searched for mindfulness-based therapy registrations. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS were also searched for mindfulness-based therapy systematic reviews and meta-analyses. 108 (87%) of 124 published trials reported ≥1 positive outcome in the abstract, and 109 (88%) concluded that mindfulness-based therapy was effective, 1.6 times greater than the expected number of positive trials based on effect size d = 0.55 (expected number positive trials = 65.7). Of 21 trial registrations, 13 (62%) remained unpublished 30 months post-trial completion. No trial registrations adequately specified a single primary outcome measure with time of assessment. None of 36 systematic reviews and meta-analyses concluded that effect estimates were overestimated due to reporting biases. The proportion of mindfulness-based therapy trials with statistically significant results may overstate what would occur in practice.

Less is More in Antidepressant Clinical Trials: A Meta-Analysis of the Effect of Visit Frequency on Treatment Response and Drop-out

PubMed Central

Rutherford, Bret R; Cooper, Timothy M.; Persaud, Amanda; Brown, Patrick J.; Sneed, Joel R.; Roose, Steven P.

2014-01-01

Objective We investigated how the number of follow-up visits affects response rates and drop-out among patients in antidepressant trials for Major Depressive Disorder (MDD). Data Sources Medline, PsycINFO, and PubMed were searched to identify trials contrasting antidepressants to placebo or active comparator in adults with depression. The index terms “depression—drug therapy,” “depressive disorder—drug therapy,” and “antidepressant agents,” in addition to the class and individual generic name of all antidepressants were combined using the ‘or’ operator. Results were limited to 1) English language articles, 2) publication year 1985 or later, 3) age group ≥ 18, and 4) publication types including clinical trials, controlled clinical trials, meta-analysis, multi-center study, randomized controlled trial, or review. Study Selection Included articles reported trials of approved antidepressant medications for MDD in outpatients aged 18–65, were 6–12 weeks in duration, and had response rates specified using a standardized measure. Trials were excluded for enrolling inpatients, pregnant women, psychotic subjects, or those with treatment-resistant depression. These criteria allowed 9,189 articles identified in the literature review to be narrowed to 111 reports. Data extraction Demographic characteristics, the number of study visits planned in each treatment cell, duration of active treatment, attrition rates, and response rates to medication and placebo were entered into a database. Results In a multilevel meta-analysis, active medication vs. placebo (OR 1.96, p < 0.001), active comparator vs. placebo-controlled study design (OR 1.82, p < 0.001), and longer vs. shorter duration (OR 1.87, p < 0.001) were associated with significantly increased odds of treatment response. After controlling for these variables, the number of study visits did not significantly influence response rates (OR 0.97, p = 0.877). The odds of drop-out were significantly decreased for active comparator vs. placebo-controlled trials (OR 0.67, p = 0.002) and longer vs. shorter duration trials (OR 0.54, p = 0.035), while increasing numbers of study visits significantly increased the odds of participant drop-out (OR 2.77, p < 0.001). Conclusion Visit schedules that are much more frequent than are commonly practiced in the community treatment of depression may increase the expense of clinical trials and make them less generalizable to standard clinical treatment. PMID:23945448

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.

A cluster randomized controlled trial of the Promoting Alternative Thinking Strategies (PATHS) curriculum.

PubMed

Humphrey, Neil; Barlow, Alexandra; Wigelsworth, Michael; Lendrum, Ann; Pert, Kirsty; Joyce, Craig; Stephens, Emma; Wo, Lawrence; Squires, Garry; Woods, Kevin; Calam, Rachel; Turner, Alex

2016-10-01

This randomized controlled trial (RCT) evaluated the efficacy of the Promoting Alternative Thinking Strategies curriculum (PATHS; Kusche & Greenberg, 1994) as a means to improve children's social-emotional competence (assessed via the Social Skills Improvement System (SSIS); Gresham & Elliot, 2008) and mental health outcomes (assessed via the Strengths and Difficulties Questionnaire (SDQ); Goodman, 1997). Forty-five schools in Greater Manchester, England, were randomly assigned to treatment and control groups. Allocation was balanced by proportions of children eligible for free school meals and speaking English as an additional language via minimization. Children (N=4516) aged 7-9years at baseline in the participating schools were the target cohort. During the two-year trial period, teachers of this cohort in schools allocated to the intervention group delivered the PATHS curriculum, while their counterparts in the control group continued their usual provision. Teachers in PATHS schools received initial training and on-going support and assistance from trained coaches. Hierarchical linear modeling of outcome data was undertaken to identify both primary (e.g., for all children) and secondary (e.g., for children classified as "at-risk") intervention effects. A primary effect of the PATHS curriculum was found, demonstrating increases in teacher ratings of changes in children's social-emotional competence. Additionally, secondary effects of PATHS were identified, showing reductions in teacher ratings of emotional symptoms and increases in pro-social behavior and child ratings of engagement among children identified as at-risk at baseline. However, our analyses also identified primary effects favoring the usual provision group, showing reductions in teacher ratings of peer problems and emotional symptoms, and secondary effects demonstrating reductions in teacher ratings of conduct problems and child ratings of co-operation among at-risk children. Effect sizes were small in all cases. These mixed findings suggest that social and emotional learning interventions such as PATHS may not be as efficacious when implemented outside their country of origin and evaluated in independent trials. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

[Systematic Review of the Application of Complementary and Alternative Medicine and their Potential Therapeutic Benefits in the Treatment of Ophthalmology Patients].

PubMed

Welte, A K; Hahn, U; Büssing, A; Krummenauer, F

2017-05-01

Purpose A systematic review was carried out of the reported therapeutic effects of complementary and alternative medicine methods as supplementary or primary treatments for patients suffering from glaucoma, cataract or age-related macular degeneration (AMD). Material and Methods For the years 1990 to 2013, the following databases were screened for reports of the application of complementary and alternative treatments: PubMed, Cochrane Library, EMBASE, CAMbase and AMED. Both randomised and prospective non-randomised patient trials were included in the review; results were evaluated in the following classes: "phytotherapy", "acupuncture/acupressure", "biofeedback" and "other alternative treatments". The studies were evaluated by measures of clinical effect, statistical significance (p value and/or confidence interval) and the underlying trial design. Results 30 clinical trials were included, including 13 on glaucoma, 5 on cataract and 12 on AMD patients. These trials were based on patient numbers of 6 - 332, 27 - 157 and 6 - 328 patients, respectively. Phytotherapy was applied in 14 trials, including 6 on glaucoma patients (all 6 with a controlled design, and 3 of which reporting statistically significant results); 5 trials were on cataract patients (3 with a controlled design and 2 with a significant result) and 3 on AMD patients (only 1 with a controlled design, with a significant result). Acupuncture/acupressure was investigated in 9 trials, 5 on glaucoma patients (3 with a controlled design, 1 with a significant result); no acupuncture/acupressure trial was found in cataract patients, but 4 trials in AMD patients (none with a controlled design). Biofeedback was studied in 4 trials, all on AMD patients (only one with a controlled design, without statistically significant findings). Conclusion Despite its rigorous inclusion criteria, this review identified several clinical trials on complementary and alternative medicine in ophthalmological patients. Phytotherapeutic methods gave significant results in half of the reported controlled trials, whereas there were few significant benefits with acupuncture or acupressure. Georg Thieme Verlag KG Stuttgart · New York.

A Written Language Intervention for At-Risk Second Grade Students: A Randomized Controlled Trial of the Process Assessment of the Learner Lesson Plans in a Tier 2 Response-to-Intervention (RtI) Model

ERIC Educational Resources Information Center

Hooper, Stephen R.; Costa, Lara-Jeane C.; McBee, Matthew; Anderson, Kathleen L.; Yerby, Donna Carlson; Childress, Amy; Knuth, Sean B.

2013-01-01

In a randomized controlled trial, 205 students were followed from grades 1 to 3 with a focus on changes in their writing trajectories following an evidence-based intervention during the spring of second grade. Students were identified as being at-risk (n = 138), and then randomized into treatment (n = 68) versus business-as-usual conditions (n =…

Stakeholders' views on the ethical challenges of pragmatic trials investigating pharmaceutical drugs.

PubMed

Kalkman, Shona; van Thiel, Ghislaine J M W; Grobbee, Diederick E; Meinecke, Anna-Katharina; Zuidgeest, Mira G P; van Delden, Johannes J M

2016-08-22

We explored the views of key stakeholders to identify the ethical challenges of pragmatic trials investigating pharmaceutical drugs. A secondary aim was to capture stakeholders' attitudes towards the implementation of pragmatic trials in the drug development process. We conducted semistructured, in-depth interviews among individuals from different key stakeholder groups (academia and independent research institutions, the pharmaceutical industry, regulators, Health Technology Assessment (HTA) agencies and patients' organizations) through telephone or face-to-face sessions. Interviews were structured around the question "what challenges were experienced or perceived during the design, conduct and/or review of pragmatic trials." Respondents were additionally asked about their views on implementation of pragmatic trials in the drug development process. Thematic analysis was used to identify the ethically relevant features across data sets. We interviewed 34 stakeholders in 25 individual sessions and four group sessions. The four perceived challenges of ethical relevance were: (1) less controlled conditions creating safety concerns, (2) comparison with usual care potentially compromising clinical equipoise, (3) tailored or waivers of informed consent affecting patient autonomy, and (4) minimal interference with "real-world" practice reducing the knowledge value of trial results. We identified stakeholder concerns regarding risk assessment, use of suboptimal usual care as a comparator, tailoring of informed consent procedures and ensuring the social value of pragmatic trials. These concerns increased when respondents were asked about pragmatic trials conducted before market authorization.

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.

Educational interventions to improve screening mammography interpretation: a randomized, controlled trial

PubMed Central

BM, Geller; A, Bogart; PA, Carney; EA, Sickles; RA, Smith; B, Monsees; LW, Bassett; DM, Buist; K, Kerlikowske; T, Onega; B, Yankaskas; S, Haneuse; DA, Hill; M, Wallis; DL, Miglioretti

2014-01-01

Purpose Conduct a randomized controlled trial of educational interventions to improve performance of screening mammography interpretation. Materials and Methods We randomly assigned physicians who interpret mammography to one of three groups: (1) self-paced DVD; (2) live, expert-led educational session; or (3) control. The DVD and live interventions used mammography cases of varying difficulty and associated teaching points. Interpretive performance was compared using a pre-/post-test design. Sensitivity, specificity, and positive predictive value (PPV) were calculated relative to two outcomes: cancer status and consensus of three experts about recall, and each were compared using logistic regression adjusting for pre-test performance. Results 102 radiologists completed all aspects of the trial. After adjustment for pre-intervention performance, the odds of improved sensitivity for correctly identifying a lesion relative to expert recall were 1.34 times higher for DVD participants than controls (95% confidence interval [CI]: 1.00, 1.81; P=0.050). The odds of improved PPV for correctly identifying a lesion relative to both expert recall (odds ratio [OR]=1.94, 95% CI: 1.24, 3.05; P=0.004) and cancer status (OR=1.81, 95% CI: 1.01, 3.23; P=0.045) were significantly improved for DVD participants compared to controls with no significant change in specificity. For the live-intervention group, specificity was significantly lower than the control group (OR relative to expert recall=0.80; 95% CI: 0.64, 1.00; P=0.048; OR relative to cancer=0.79; 95% CI: 0.65, 0.95; P=0.015). Conclusion In this randomized controlled trial, the DVD educational intervention resulted in a significant improvement in mammography interpretive screening performance on a test-set, which could translate into improved clinical interpretative performance. PMID:24848854

Educational interventions to improve screening mammography interpretation: a randomized controlled trial.

PubMed

Geller, Berta M; Bogart, Andy; Carney, Patricia A; Sickles, Edward A; Smith, Robert; Monsees, Barbara; Bassett, Lawrence W; Buist, Diana M; Kerlikowske, Karla; Onega, Tracy; Yankaskas, Bonnie C; Haneuse, Sebastien; Hill, Deirdre; Wallis, Matthew G; Miglioretti, Diana

2014-06-01

The objective of our study was to conduct a randomized controlled trial of educational interventions that were created to improve performance of screening mammography interpretation. We randomly assigned physicians who interpret mammography to one of three groups: self-paced DVD, live expert-led educational seminar, or control. The DVD and seminar interventions used mammography cases of varying difficulty and provided associated teaching points. Interpretive performance was compared using a pretest-posttest design. Sensitivity, specificity, and positive predictive value (PPV) were calculated relative to two outcomes: cancer status and consensus of three experts about recall. The performance measures for each group were compared using logistic regression adjusting for pretest performance. One hundred two radiologists completed all aspects of the trial. After adjustment for preintervention performance, the odds of improved sensitivity for correctly identifying a lesion relative to expert recall were 1.34 times higher for DVD participants than for control subjects (95% CI, 1.00-1.81; p = 0.050). The odds of an improved PPV for correctly identifying a lesion relative to both expert recall (odds ratio [OR] = 1.94; 95% CI, 1.24-3.05; p = 0.004) and cancer status (OR = 1.81; 95% CI, 1.01-3.23; p = 0.045) were significantly improved for DVD participants compared with control subjects, with no significant change in specificity. For the seminar group, specificity was significantly lower than the control group (OR relative to expert recall = 0.80; 95% CI, 0.64-1.00; p = 0.048; OR relative to cancer status = 0.79; 95% CI, 0.65-0.95; p = 0.015). In this randomized controlled trial, the DVD educational intervention resulted in a significant improvement in screening mammography interpretive performance on a test set, which could translate into improved interpretative performance in clinical practice.

Pre-cue Fronto-Occipital Alpha Phase and Distributed Cortical Oscillations Predict Failures of Cognitive Control

PubMed Central

Hamm, Jordan P.; Dyckman, Kara A.; McDowell, Jennifer E.; Clementz, Brett A.

2012-01-01

Cognitive control is required for correct performance on antisaccade tasks, including the ability to inhibit an externally driven ocular motor repsonse (a saccade to a peripheral stimulus) in favor of an internally driven ocular motor goal (a saccade directed away from a peripheral stimulus). Healthy humans occasionally produce errors during antisaccade tasks, but the mechanisms associated with such failures of cognitive control are uncertain. Most research on cognitive control failures focuses on post-stimulus processing, although a growing body of literature highlights a role of intrinsic brain activity in perceptual and cognitive performance. The current investigation used dense array electroencephalography and distributed source analyses to examine brain oscillations across a wide frequency bandwidth in the period prior to antisaccade cue onset. Results highlight four important aspects of ongoing and preparatory brain activations that differentiate error from correct antisaccade trials: (i) ongoing oscillatory beta (20–30Hz) power in anterior cingulate prior to trial initiation (lower for error trials), (ii) instantaneous phase of ongoing alpha-theta (7Hz) in frontal and occipital cortices immediately before trial initiation (opposite between trial types), (iii) gamma power (35–60Hz) in posterior parietal cortex 100 ms prior to cue onset (greater for error trials), and (iv) phase locking of alpha (5–12Hz) in parietal and occipital cortices immediately prior to cue onset (lower for error trials). These findings extend recently reported effects of pre-trial alpha phase on perception to cognitive control processes, and help identify the cortical generators of such phase effects. PMID:22593071

Establishing Evidence-Based Indications for Proton Therapy: An Overview of Current Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mishra, Mark V., E-mail: mmishra@umm.edu; Aggarwal, Sameer; Bentzen, Soren M.

Purpose: To review and assess ongoing proton beam therapy (PBT) clinical trials and to identify major gaps. Methods and Materials: Active PBT clinical trials were identified from (clinicaltrials.gov) and the World Health Organization International Clinical Trials Platform Registry. Data on clinical trial disease site, age group, projected patient enrollment, expected start and end dates, study type, and funding source were extracted. Results: A total of 122 active PBT clinical trials were identified, with target enrollment of >42,000 patients worldwide. Ninety-six trials (79%), with a median planned sample size of 68, were classified as interventional studies. Observational studies accounted for 21% ofmore » trials but 71% (n=29,852) of planned patient enrollment. The most common PBT clinical trials focus on gastrointestinal tract tumors (21%, n=26), tumors of the central nervous system (15%, n=18), and prostate cancer (12%, n=15). Five active studies (lung, esophagus, head and neck, prostate, breast) will randomize patients between protons and photons, and 3 will randomize patients between protons and carbon ion therapy. Conclusions: The PBT clinical trial portfolio is expanding rapidly. Although the majority of ongoing studies are interventional, the majority of patients will be accrued to observational studies. Future efforts should focus on strategies to encourage optimal patient enrollment and retention, with an emphasis on randomized, controlled trials, which will require support from third-party payers. Results of ongoing PBT studies should be evaluated in terms of comparative effectiveness, as well as incremental effectiveness and value offered by PBT in comparison with conventional radiation modalities.« less

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.

The effect of replacing saturated fat with mostly n-6 polyunsaturated fat on coronary heart disease: a meta-analysis of randomised controlled trials.

PubMed

Hamley, Steven

2017-05-19

A cornerstone of conventional dietary advice is the recommendation to replace saturated fatty acids (SFA) with mostly n-6 polyunsaturated fatty acids (PUFA) to reduce the risk of coronary heart disease (CHD). Many clinical trials aimed to test this advice and have had their results pooled in several meta-analyses. However, earlier meta-analyses did not sufficiently account for major confounding variables that were present in some of those trials. Therefore, the aim of the study was to account for the major confounding variables in the diet heart trials, and emphasise the results from those trials that most accurately test the effect of replacing SFA with mostly n-6 PUFA. Clinical trials were identified from earlier meta-analyses. Relevant trials were categorised as 'adequately controlled' or 'inadequately controlled' depending on whether there were substantial dietary or non-dietary differences between the experimental and control groups that were not related to SFA or mostly n-6 PUFA intake, then were subject to different subgroup analyses. When pooling results from only the adequately controlled trials there was no effect for major CHD events (RR = 1.06, CI = 0.86-1.31), total CHD events (RR = 1.02, CI = 0.84-1.23), CHD mortality (RR = 1.13, CI = 0.91-1.40) and total mortality (RR = 1.07, CI = 0.90-1.26). Whereas, the pooled results from all trials, including the inadequately controlled trials, suggested that replacing SFA with mostly n-6 PUFA would significantly reduce the risk of total CHD events (RR = 0.80, CI = 0.65-0.98, P = 0.03), but not major CHD events (RR = 0.87, CI = 0.70-1.07), CHD mortality (RR = 0.90, CI = 0.70-1.17) and total mortality (RR = 1.00, CI = 0.90-1.10). Available evidence from adequately controlled randomised controlled trials suggest replacing SFA with mostly n-6 PUFA is unlikely to reduce CHD events, CHD mortality or total mortality. The suggestion of benefits reported in earlier meta-analyses is due to the inclusion of inadequately controlled trials. These findings have implications for current dietary recommendations.

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.

Birth Control in Clinical Trials

PubMed Central

Stewart, J.; Beyer, B. K.; Chadwick, K.; De Schaepdrijver, L.; Desai, M.; Enright, B.; Foster, W.; Hui, J. Y.; Moffat, G. J.; Tornesi, B.; Van Malderen, K.; Wiesner, L.; Chen, C. L.

2015-01-01

The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology Technical Committee sponsored a pharmaceutical industry survey on current industry practices for contraception use during clinical trials. The objectives of the survey were to improve our understanding of the current industry practices for contraception requirements in clinical trials, the governance processes set up to promote consistency and/or compliance with contraception requirements, and the effectiveness of current contraception practices in preventing pregnancies during clinical trials. Opportunities for improvements in current practices were also considered. The survey results from 12 pharmaceutical companies identified significant variability among companies with regard to contraception practices and governance during clinical trials. This variability was due primarily to differences in definitions, areas of scientific uncertainty or misunderstanding, and differences in company approaches to enrollment in clinical trials. The survey also revealed that few companies collected data in a manner that would allow a retrospective understanding of the reasons for failure of birth control during clinical trials. In this article, suggestions are made for topics where regulatory guidance or scientific publications could facilitate best practice. These include provisions for a pragmatic definition of women of childbearing potential, guidance on how animal data can influence the requirements for male and female birth control, evidence-based guidance on birth control and pregnancy testing regimes suitable for low- and high-risk situations, plus practical methods to ascertain the risk of drug-drug interactions with hormonal contraceptives. PMID:27042398

Opinions of researchers based in the UK on recruiting subjects from developing countries into randomized controlled trials.

PubMed

Newton, Sam K; Appiah-Poku, John

2007-12-01

Explaining technical terms in consent forms prior to seeking informed consent to recruit into trials can be challenging in developing countries, and more so when the studies are randomized controlled trials. This study was carried out to examine the opinions of researchers on ways of dealing with these challenges in developing countries. Recorded in-depth interviews with 12 lecturers and five doctoral students, who had carried out research in developing countries, at a leading school of public health in the United Kingdom. A purposive, snowballing approach was used to identify interviewees. Researchers were divided on the feasibility of explaining technical trials in illiterate populations; the majority of them held the view that local analogies could be used to explain these technical terms. Others were of the opinion that this could not be done since it was too difficult to explain technical trials, such as randomized controlled trials, even to people in developed countries. Researchers acknowledged the difficulty in explaining randomized controlled trials but it was also their perception that this was an important part of the ethics of the work of scientific research involving human subjects. These difficulties notwithstanding, efforts should be made to ensure that subjects have sufficient understanding to consent, taking into account the fact that peculiar situations in developing countries might compound this difficulty.

The effectiveness and cost-evaluation of manual therapy and physical therapy in patients with sub-acute and chronic non specific neck pain. Rationale and design of a Randomized Controlled Trial (RCT)

PubMed Central

2010-01-01

Background Manual Therapy applied to patients with non specific neck pain has been investigated several times. In the Netherlands, manual therapy as applied according to the Utrecht School of Manual Therapy (MTU) has not been the subject of a randomized controlled trial. MTU differs in diagnoses and treatment from other forms of manual therapy. Methods/Design This is a single blind randomized controlled trial in patients with sub-acute and chronic non specific neck pain. Patients with neck complaints existing for two weeks (minimum) till one year (maximum) will participate in the trial. 180 participants will be recruited in thirteen primary health care centres in the Netherlands. The experimental group will be treated with MTU during a six week period. The control group will be treated with physical therapy (standard care, mainly active exercise therapy), also for a period of six weeks. Primary outcomes are Global Perceived Effect (GPE) and functional status (Neck Disability Index (NDI-DV)). Secondary outcomes are neck pain (Numeric Rating Scale (NRS)), Eurocol, costs and quality of life (SF36). Discussion This paper presents details on the rationale of MTU, design, methods and operational aspects of the trial. Trial registration ClinicalTrials.gov Identifier: NCT00713843 PMID:20096136

A mixed methods study to assess the feasibility of a randomised controlled trial of invasive urodynamic testing versus clinical assessment and non-invasive tests prior to surgery for stress urinary incontinence in women: the INVESTIGATE-I study.

PubMed

Hilton, Paul; Armstrong, Natalie; Brennand, Catherine; Howel, Denise; Shen, Jing; Bryant, Andrew; Tincello, Douglas G; Lucas, Malcolm G; Buckley, Brian S; Chapple, Christopher R; Homer, Tara; Vale, Luke; McColl, Elaine

2015-09-08

The position of invasive urodynamic testing (IUT) in diagnostic pathways for urinary incontinence is unclear, and systematic reviews have called for further trials evaluating clinical utility. The objective of this study was to inform the decision whether to proceed to a definitive randomised trial of IUT compared to clinical assessment with non-invasive tests, prior to surgery in women with stress urinary incontinence (SUI) or stress-predominant mixed urinary incontinence (MUI). A mixed methods study comprising a pragmatic multicentre randomised pilot trial, a qualitative face-to face interview study with patients eligible for the trial, an exploratory economic evaluation including value of information study, a survey of clinicians' views about IUT, and qualitative telephone interviews with purposively sampled survey respondents. Only the first and second of these elements are reported here. Trial participants were randomised to either clinical assessment with non-invasive tests (control arm) or clinical assessment with non-invasive tests plus IUT (intervention arm). The main outcome measures of these feasibility studies were confirmation that units can identify and recruit eligible women, acceptability of investigation strategies and data collection tools, and acquisition of outcome data to determine the sample size for a definitive trial. The primary outcome proposed for a definitive trial was ICIQ-FLUTS (total score) 6 months after surgery or the start of nonsurgical treatment. Of 284 eligible women, 222 (78%) were recruited, 165/219 (75%) returned questionnaires at baseline, and 125/200 returned them (63%) at follow-up. Most women underwent surgery; management plans were changed in 19 (19%) participants following IUT. Participants interviewed were positive about the trial and the associated documentation. All elements of a definitive trial were rehearsed. Such a trial would require between 232 and 922 participants, depending on the target difference in the primary outcome. We identified possible modifications to our protocol for application in a definitive trial including clarity over inclusion/exclusions, screening processes, reduction in secondary outcomes, and modification to patient questionnaire booklets and bladder diaries. A definitive trial of IUT versus clinical assessment prior to surgery for SUI or stress predominant MUI is feasible and remains relevant. Current Controlled Trials: ISRCTN 71327395, registered 7 June 2010.

Effect of Treatment Delay, Stroke Type, and Thrombolysis on the Effect of Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome after Acute Stroke: A Systematic Review and Meta-Analysis of Individual Patient from Randomised Trials.

PubMed

Bath, Philip M; Woodhouse, Lisa; Krishnan, Kailash; Anderson, Craig; Berge, Eivind; Ford, Gary A; Robinson, Thompson G; Saver, Jeffrey L; Sprigg, Nikola; Wardlaw, Joanna M; In Acute Stroke Collaboration Basc, Blood Pressure

2016-01-01

Background. Nitric oxide (NO) donors are a candidate treatment for acute stroke and two trials have suggested that they might improve outcome if administered within 4-6 hours of stroke onset. We assessed the safety and efficacy of NO donors using individual patient data (IPD) from completed trials. Methods. Randomised controlled trials of NO donors in patients with acute or subacute stroke were identified and IPD sought from the trialists. The effect of NO donor versus control on functional outcome was assessed using the modified Rankin scale (mRS) and death, by time to randomisation. Secondary outcomes included measures of disability, mood, and quality of life. Results. Five trials (4,197 participants) were identified, all involving glyceryl trinitrate (GTN). Compared with control, GTN lowered blood pressure by 7.4/3.3 mmHg. At day 90, GTN did not alter any clinical measures. However, in 312 patients randomised within 6 hours of stroke onset, GTN was associated with beneficial shifts in the mRS (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.34-0.78) and reduced death (OR 0.32, 95% CI 0.14-0.78). Conclusions. NO donors do not alter outcome in patients with recent stroke. However, when administered within 6 hours, NO donors might improve outcomes in both ischaemic and haemorrhagic stroke.

No. 263-Maternity Leave in Normal Pregnancy.

PubMed

Leduc, Dean

2017-10-01

To assist maternity care providers in recognizing and discussing health- and illness-related issues in pregnancy and their relationship to maternity benefits. Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in 2009 using appropriate controlled vocabulary (e.g., maternity benefits) and key words (e.g., maternity, benefits, pregnancy). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to December 2009. Grey (unpublished) literature was identified through searching the web sites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Copyright © 2017. Published by Elsevier Inc.

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

Mindfulness interventions for psychosis: a systematic review of the literature.

PubMed

Aust, J; Bradshaw, T

2017-02-01

WHAT IS KNOWN ON THE SUBJECT?: Psychosis and the more specific diagnosis of schizophrenia constitute a major psychiatric disorder which impacts heavily on the self-esteem, functioning and quality of life of those affected. A number of mindfulness therapies have been developed in recent years, showing promising results when used with people with the disorder. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This review of the literature included only randomized controlled trials (RCTs), rather than other typically less robust methods of research (e.g. case studies, noncontrolled studies). WHAT ARE THE IMPLICATIONS FOR PRACTICE?: We concluded that mindfulness therapies can be safely used with people with psychosis and that they provide a number of therapeutic benefits compared with routine care and, in some cases, other interventions. Larger, methodologically improved trials are now recommended to evaluate the benefits of mindfulness therapies further. Introduction A growing number of mindfulness interventions are being used with individuals with psychosis. These therapies employ elements of acceptance and compassion in addition to mindfulness. A number of randomized controlled trials (RCTs) of these interventions have emerged in recent years, but no review of these latest trials exists. Question 'For individuals with psychosis, are mindfulness interventions more effective than treatment as usual or an alternative intervention, in improving patient-related outcomes as demonstrated in RCTs?' Method We undertook a systematic review of randomized controlled studies of mindfulness interventions for psychosis and schizophrenia (MIps). Studies were identified by searching the databases Medline, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, and Allied and Complementary Medicine. Findings The review identified 11 RCTs investigating eight mindfulness interventions. Significant improvements were reported on a number of measures, although gains were mostly smaller in trials employing well-designed controls and where assessors were blind to treatment allocation. There was considerable heterogeneity amongst trials in the diversity of treatments reviewed and the range of outcomes assessed. Implications for Practice The findings suggest MIps are feasible for individuals with psychosis and provide a number of significant benefits over routine care and, in some cases, other interventions. © 2016 John Wiley & Sons Ltd.

Informing real-world practice with real-world evidence: the value of PRECIS-2.

PubMed

Neta, Gila; Johnson, Karin E

2018-05-21

Real-world evidence is needed to inform real-world practice. Pragmatic controlled trials are intended to provide such evidence by assessing the effectiveness of medicines and other interventions in real-world settings, as opposed to explanatory trials that assess efficacy in highly controlled settings. Dal-Ré and colleagues (BMC Med 16:49, 2018) recently performed a literature review of studies published between 2014 and 2017 to assess the degree to which studies that self-identified as pragmatic were truly so. The authors found that over one-third of randomized controlled trials of drugs and biologics that were self-labeled as pragmatic used placebo controls (as opposed to usual care), tested medicines before licensing, or were conducted in a single site. Further, they proposed that, in order to improve the reliability of the 'pragmatic' label, investigators should assess their trials using the PRECIS-2 tool upon submission to funders, ethics boards, or journals. We appreciate the value of PRECIS-2 as an indicator to assess the pragmatic versus explanatory features in a trial, and we herein highlight the potential challenges and opportunities that may arise with its systematic and widespread use.

An assessment of quality characteristics of randomised control trials published in dental journals.

PubMed

Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

2010-09-01

The purpose of this study was to investigate the quality of reporting of randomised clinical trials (RCTs) published in dental specialty journals. The journals possessing the highest impact factor (2008 data) in the six major dental specialties were included in the study. The contents of the 24 most recent issues of each journal were hand-searched and research articles identified as randomised controlled trials (RCTs) were selected. Quality evaluation was performed using the modified Consolidated Standards of Reporting Trials (CONSORT) statement checklist. The data were analysed using descriptive statistics followed by univariate and multivariate examination of statistical associations (alpha=0.05). Ninety-five RCTs were identified with generally suboptimal scores on quality reporting on key CONSORT areas. Significant differences were found among journals with the Journal of Clinical Periodontology achieving the highest score, followed by the American Journal of Orthodontics and Dentofacial Orthopedics. There was a positive association between quality score and number of authors, involvement of statistician/epidemiologist, and multicentre trials. The quality scores of RCTs in major dental journals are considered suboptimal in key CONSORT areas. This receives critical importance considering that improved quality of RCTs is a fundamental prerequisite for improved dental care. Copyright 2010 Elsevier Ltd. All rights reserved.

Effects of superfoods on risk factors of metabolic syndrome: a systematic review of human intervention trials.

PubMed

van den Driessche, José J; Plat, Jogchum; Mensink, Ronald P

2018-04-25

Functional foods can be effective in the prevention of metabolic syndrome and subsequently the onset of cardiovascular diseases and type II diabetes mellitus. More recently, however, another term was introduced to describe foods with additional health benefits: "superfoods", for which, to date, no generally accepted definition exists. Nonetheless, their consumption might contribute to the prevention of metabolic syndrome, for example due to the presence of potentially bioactive compounds. This review provides an overview of controlled human intervention studies with foods described as "superfoods" and their effects on metabolic syndrome parameters. First, an Internet search was performed to identify foods described as superfoods. For these superfoods, controlled human intervention trials were identified until April 2017 investigating the effects of superfood consumption on metabolic syndrome parameters: waist circumference or BMI, blood pressure, or concentrations of HDL cholesterol, triacylglycerol or glucose. Seventeen superfoods were identified, including a total of 113 intervention trials: blueberries (8 studies), cranberries (8), goji berries (3), strawberries (7), chili peppers (3), garlic (21), ginger (10), chia seed (5), flaxseed (22), quinoa (1), cocoa (16), maca (1), spirulina (7), wheatgrass (1), acai berries (0), hemp seed (0) and bee pollen (0). Overall, only limited evidence was found for the effects of the foods described as superfoods on metabolic syndrome parameters, since results were not consistent or the number of controlled intervention trials was limited. The inconsistencies might have been related to intervention-related factors, such as duration or dose. Furthermore, conclusions may be different if other health benefits are considered.

Maximising the value of combining qualitative research and randomised controlled trials in health research: the QUAlitative Research in Trials (QUART) study--a mixed methods study.

PubMed

O'Cathain, Alicia; Thomas, Kate J; Drabble, Sarah J; Rudolph, Anne; Goode, Jackie; Hewison, Jenny

2014-06-01

Researchers sometimes undertake qualitative research with randomised controlled trials (RCTs) of health interventions. To systematically explore how qualitative research is being used with trials and identify ways of maximising its value to the trial aim of providing evidence of effectiveness of health interventions. A sequential mixed methods study with four components. (1) Database search of peer-reviewed journals between January 2008 and September 2010 for articles reporting the qualitative research undertaken with specific trials, (2) systematic search of database of registered trials to identify studies combining qualitative research and trials, (3) survey of 200 lead investigators of trials with no apparent qualitative research and (4) semistructured telephone interviews with 18 researchers purposively sampled from the first three methods. Qualitative research was undertaken with at least 12% of trials. A large number of articles reporting qualitative research undertaken with trials (n=296) were published between 2008 and 2010. A total of 28% (82/296) of articles reported qualitative research undertaken at the pre-trial stage and around one-quarter concerned drugs or devices. The articles focused on 22 aspects of the trial within five broad categories. Some focused on more than one aspect of the trial, totalling 356 examples. The qualitative research focused on the intervention being trialled (71%, 254/356), the design and conduct of the trial (15%, 54/356), the outcomes of the trial (1%, 5/356), the measures used in the trial (3%, 10/356), and the health condition in the trial (9%, 33/356). The potential value of the qualitative research to the trial endeavour included improving the external validity of trials and facilitating interpretation of trial findings. This value could be maximised by using qualitative research more at the pre-trial stage and reporting findings with explicit attention to the implications for the trial endeavour. During interviews, three models of study were identified: qualitative research as peripheral to the trial, qualitative research as an 'add-on' to the trial and a study with qualitative research and trial as essential components, with the third model offering more opportunity to maximise the value of the qualitative research. Interviewees valued the use of qualitative research with trials and identified team structures and wider structural issues which gave more value to the trial than the qualitative research as barriers to maximising the value of the qualitative research. A large number of articles were published between 2008 and 2010, addressing a wide range of aspects of trials. There were examples of this research affecting the trial by facilitating interpretation of trial findings, developing and refining interventions for testing in the trial and changing the measures used in the trial. However, researchers were not necessarily maximising the value of qualitative research undertaken with trials to the endeavour of generating evidence of effectiveness of health interventions. Researchers can maximise value by promoting its use at the pre-trial stage to ensure that the intervention and trial conduct is optimised at the main trial stage, being explicit about the conclusions for the trial endeavour in peer-reviewed journal articles reporting the qualitative research and valuing the contribution of the qualitative research as much as the trial. Future recommendations for researchers include: plan the qualitative research, design and implement studies not trials, use qualitative research at the feasibility and pilot stage of trials, be explicit in publications about the impact of the qualitative research on the trial and implications for the trial endeavour, undertake in-depth qualitative research, allow qualitative research to take a challenging role and develop a learning environment around the use of qualitative research and trials. This project was funded by the Medical Research Council (MRC) as part of the MRC-National Institute for Health Research Methodology Research programme.

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.

Effect of Cosmos caudatus (Ulam raja) supplementation in patients with type 2 diabetes: Study protocol for a randomized controlled trial.

PubMed

Cheng, Shi-Hui; Ismail, Amin; Anthony, Joseph; Ng, Ooi Chuan; Hamid, Azizah Abdul; Yusof, Barakatun-Nisak Mohd

2016-02-27

Type 2 diabetes mellitus is a major health threat worldwide. Cosmos caudatus is one of the medicinal plants used to treat type 2 diabetes. Therefore, this study aims to determine the effectiveness and safety of C. caudatus in patients with type 2 diabetes. Metabolomic approach will be carried out to compare the metabolite profiles between C. Caudatus treated diabetic patients and diabetic controls. This is a single-center, randomized, controlled, two-arm parallel design clinical trial that will be carried out in a tertiary hospital in Malaysia. In this study, 100 patients diagnosed with type 2 diabetes will be enrolled. Diabetic patients who meet the eligibility criteria will be randomly allocated to two groups, which are diabetic C. caudatus treated(U) group and diabetic control (C) group. Primary and secondary outcomes will be measured at baseline, 4, 8, and 12 weeks. The serum and urine metabolome of both groups will be examined using proton NMR spectroscopy. The study will be the first randomized controlled trial to assess whether C. caudatus can confer beneficial effect in patients with type 2 diabetes. The results of this trial will provide clinical evidence on the effectiveness and safety of C. caudatus in patients with type 2 diabetes. ClinicalTrials.gov identifier: NCT02322268.

Biofeedback therapy in fecal incontinence and constipation.

PubMed

Enck, P; Van der Voort, I R; Klosterhalfen, S

2009-11-01

We examine the collected evidence for efficacy of biofeedback therapy (BFT) in incontinence and constipation by means of meta-analysis of randomized controlled trials. PubMed search was performed to identify treatment trials that match quality criteria (adequate control groups, randomization). They were entered into meta-analyses using fixed effect models and computing odds ratio (OR) and 95% confidence interval (CI) of treatment effects. For constipation, eight BFT trials were identified. In four trials, electromyographic (EMG) BFT was compared to non-BFT treatments (laxatives, placebo, sham training and botox injection), while in the remaining four studies EMG BFT was compared to other BFT (balloon pressure, verbal feedback) modes. Meta-analyses revealed superiority of BFT to non-BFT (OR: 3.657; 95% CI: 2.127-6.290, P < 0.001) but equal efficacy of EMG BFT to other BF applications (OR: 1.436; CI: 0.692-3.089; P = 0.319). For fecal incontinence, a total of 11 trials were identified, of which six compared BFT to other treatment options (sensory training, pelvic floor exercise and electrical stimulation) and five compared one BFT option to other modalities of BFT. BFT was equal effective than non-BFT therapy (OR: 1.189, CI: 0.689-2.051, P = 0.535). No difference was found when various modes BFT were compared (OR: 1.278, CI: 0.736-2.220, P = 0.384). Included trials showed a substantial lack of quality and harmonization, e.g. variable endpoints and missing psychological assessment across studies. BFT for pelvic floor dyssynergia shows substantial specific therapeutic effect while BFT for incontinence is still lacking evidence for efficacy. However, in both conditions the mode of BFT seems to play a minor role.

The effect of mud therapy on pain relief in patients with knee osteoarthritis: a meta-analysis of randomized controlled trials.

PubMed

Liu, Hua; Zeng, Chao; Gao, Shu-guang; Yang, Tuo; Luo, Wei; Li, Yu-sheng; Xiong, Yi-lin; Sun, Jin-peng; Lei, Guang-hua

2013-10-01

A meta-analysis was conducted to examine the effect of mud therapy on pain relief in patients with knee osteoarthritis (OA). A detailed search of PubMed®/MEDLINE® was undertaken to identify randomized controlled trials and prospective comparative studies published before 9 March 2013 that compared mud therapy with control group treatments in patients with knee OA. A quantitative meta-analysis of seven studies (410 patients) was performed. There was a significant difference between the groups in the visual analogue scale pain score (standardized mean difference [SMD] -0.73) and Western Ontario and McMaster Universities Osteoarthritis Index pain score (SMD -0.30), with differences in favour of mud therapy. Mud therapy is a favourable option for pain relief in patients with knee OA. Additional high-quality randomized controlled trials need to be conducted to explore this issue further and to confirm this conclusion.

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

Maintenance Cognitive Stimulation Therapy (CST) in practice: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Cognitive Stimulation Therapy (CST) is a psychosocial evidence-based group intervention for people with dementia recommended by the UK NICE guidelines. In clinical trials, CST has been shown to improve cognition and quality of life, but little is known about the best way of ensuring implementation of CST in practice settings. A recent pilot study found that a third of people who attend CST training go on to run CST in practice, but staff identified a lack of support as a key reason for the lack of implementation. Methods/design There are three projects in this study: The first is a pragmatic multi-centre, randomised controlled trial (RCT) of staff training, comparing CST training and outreach support with CST training only; the second, the monitoring and outreach trial, is a phase IV trial that evaluates implementation of CST in practice by staff members who have previously had the CST manual or attended training. Centres will be randomised to receive outreach support. The primary outcome measure for both of these trials is the number of CST sessions run for people with dementia. Secondary outcomes include the number of attenders at sessions, job satisfaction, dementia knowledge and attitudes, competency, barriers to change, approach to learning and a controllability of beliefs and the level of adherence. Focus groups will assess staff members’ perceptions of running CST groups and receiving outreach support. The third study involves monitoring centres running groups in their usual practice and looking at basic outcomes of cognition and quality of life for the person with dementia. Discussion These studies assess the effects of outreach support on putting CST into practice and running groups effectively in a variety of care settings with people with dementia; evaluate the effectiveness of CST in standard clinical practice; and identify key factors promoting or impeding the successful running of groups. Trial registration Clinical trial ISRCTN28793457. PMID:22735077

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.

Renin-angiotensin system inhibitors prevent the recurrence of atrial fibrillation: a meta-analysis of randomized controlled trials.

PubMed

Han, Min; Zhang, Yong; Sun, Shujuan; Wang, Zhongsu; Wang, Jiangrong; Xie, Xinxing; Gao, Mei; Yin, Xiangcui; Hou, Yinglong

2013-10-01

This study was designed to assess whether angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could prevent the recurrence of atrial fibrillation (AF). A systemic literature search of PubMed, EMBASE, and Cochrane Controlled Trials Register till 2012 was performed to identify randomized controlled trials involving the prevention of recurrence of AF with renin-angiotensin system blockade therapy. Subgroup analysis and meta-regression were performed. Publication bias was checked through funnel plot and Egger's test. Twenty-one randomized controlled trials including 13,184 patients with AF were identified. Overall, the recurrence of AF was significantly reduced in patients using ACEI/ARBs [odds ratio (OR), 0.43; 95% confidence interval (CI), 0.32-0.56; P < 0.00001], especially both in irbesartan subgroup (OR, 0.38; 95% CI, 0.21-0.68; P = 0.001) and in patients receiving antiarrhythmic drug (AAD) (OR, 0.37; 95% CI, 0.29-0.48; P < 0.00001), and there was no significant difference between ACEIs and ARBs (ACEIs: OR, 0.42; 95% CI, 0.31-0.57 and ARBs: OR, 0.42; 95% CI, 0.31-0.57). Moreover, it was found that the benefits of ACEI/ARBs revealed positive correlation to systolic blood pressure (regression coefficient: -0.0700257, P = 0.000) in no-AAD users. ACEI/ARBs are effective on the secondary prevention of AF, especially in patients receiving AAD and suffering from hypertension.

The REFLECT statement: methods and processes of creating reporting guidelines for randomized controlled trials for livestock and food safety.

PubMed

O'Connor, A M; Sargeant, J M; Gardner, I A; Dickson, J S; Torrence, M E; Dewey, C E; Dohoo, I R; Evans, R B; Gray, J T; Greiner, M; Keefe, G; Lefebvre, S L; Morley, P S; Ramirez, A; Sischo, W; Smith, D R; Snedeker, K; Sofos, J; Ward, M P; Wills, R

2010-01-01

The conduct of randomized controlled trials in livestock with production, health, and food-safety outcomes presents unique challenges that might not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A 2-day consensus meeting was held on November 18-19, 2008 in Chicago, IL, to achieve the objective. Before the meeting, a Web-based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food-safety researchers, livestock production specialists, journal editors, assistant editors, and associate editors. Before the meeting, the attendees completed a Web-based survey indicating which CONSORT statement items would need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines for Randomized Control Trials) statement for livestock and food safety and 22-item checklist. Fourteen items were modified from the CONSORT checklist, and an additional subitem was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health, and food-safety outcomes.

Effect of Fructose on Established Lipid Targets: A Systematic Review and Meta-Analysis of Controlled Feeding Trials

PubMed Central

Chiavaroli, Laura; de Souza, Russell J; Ha, Vanessa; Cozma, Adrian I; Mirrahimi, Arash; Wang, David D; Yu, Matthew; Carleton, Amanda J; Di Buono, Marco; Jenkins, Alexandra L; Leiter, Lawrence A; Wolever, Thomas M S; Beyene, Joseph; Kendall, Cyril W C; Jenkins, David J A; Sievenpiper, John L

2015-01-01

Background Debate over the role of fructose in mediating cardiovascular risk remains active. To update the evidence on the effect of fructose on established therapeutic lipid targets for cardiovascular disease (low-density lipoprotein cholesterol [LDL]-C, apolipoprotein B, non-high-density lipoprotein cholesterol [HDL-C]), and metabolic syndrome (triglycerides and HDL-C), we conducted a systematic review and meta-analysis of controlled feeding trials. Methods and Results MEDLINE, EMBASE, CINHAL, and the Cochrane Library were searched through July 7, 2015 for controlled feeding trials with follow-up ≥7 days, which investigated the effect of oral fructose compared to a control carbohydrate on lipids (LDL-C, apolipoprotein B, non-HDL-C, triglycerides, and HDL-C) in participants of all health backgrounds. Two independent reviewers extracted relevant data. Data were pooled using random effects models and expressed as mean difference with 95% CI. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). Eligibility criteria were met by 51 isocaloric trials (n=943), in which fructose was provided in isocaloric exchange for other carbohydrates, and 8 hypercaloric trials (n=125), in which fructose supplemented control diets with excess calories compared to the control diets alone without the excess calories. Fructose had no effect on LDL-C, non-HDL-C, apolipoprotein B, triglycerides, or HDL-C in isocaloric trials. However, in hypercaloric trials, fructose increased apolipoprotein B (n=2 trials; mean difference = 0.18 mmol/L; 95% CI: 0.05, 0.30; P=0.005) and triglycerides (n=8 trials; mean difference = 0.26 mmol/L; 95% CI: 0.11, 0.41; P<0.001). The study is limited by small sample sizes, limited follow-up, and low quality scores of the included trials. Conclusions Pooled analyses showed that fructose only had an adverse effect on established lipid targets when added to existing diets so as to provide excess calories (+21% to 35% energy). When isocalorically exchanged for other carbohydrates, fructose had no adverse effects on blood lipids. More trials that are larger, longer, and higher quality are required. Clinical Trials Registration URL: https://www.clinicaltrials.gov/. Unique Identifier: NCT01363791. PMID:26358358

Relationship of ZNF423 and CTSO with breast cancer risk in two randomised tamoxifen prevention trials.

PubMed

Brentnall, Adam R; Cuzick, Jack; Byers, Helen; Segal, Corrinne; Reuter, Caroline; Detre, Simone; Sestak, Ivana; Howell, Anthony; Powles, Trevor J; Newman, William G; Dowsett, Mitchell

2016-08-01

A case-control study from two randomised breast cancer prevention trials of tamoxifen and raloxifene (P-1 and P-2) identified single-nucleotide polymorphisms (SNPs) in or near genes ZNF423 and CTSO as factors which predict which women will derive most anti-cancer benefit from selective oestrogen receptor modulator (SERM) therapy. In this article, we further examine this question using blood samples from two randomised tamoxifen prevention trials: the International Breast Cancer Intervention Study I (IBIS-I) and the Royal Marsden trial (Marsden). A nested case-control study was designed with 2:1 matching in IBIS-I and 1:1 matching in Marsden. The OncoArray was used for genotyping and included two SNPs previously identified (rs8060157 in ZNF423 and rs10030044 near CTSO), and 102 further SNPs within the same regions. Overall, there were 369 cases and 662 controls, with 148 cases and 268 controls from the tamoxifen arms. Odds ratios were estimated by conditional logistic regression, with Wald 95 % confidence intervals. In the tamoxifen arms, the per-allele odds ratio for rs8060157 was 0.99 (95 %CI 0.73-1.34) and 1.00 (95 %CI 0.76-1.33) for rs10030044. In the placebo arm, the odds ratio was 1.10 (95 %CI 0.87-1.40) for rs8060157 and 1.01 (95 %CI 0.79-1.29) for rs10030044. There was no evidence to suggest that other SNPs in the surrounding regions of these SNPs might predict response to tamoxifen. Results from these two prevention trials do not support the earlier findings. rs8060157 in ZNF423 and rs10030044 near CTSO do not appear to predict response to tamoxifen.

Cognitive-behavioral therapy for somatization and symptom syndromes: a critical review of controlled clinical trials.

PubMed

Kroenke, K; Swindle, R

2000-01-01

Few treatments for somatization have been proven effective. In the past decade, however, clinical trials of cognitive-behavioral therapy (CBT) have been promising. Our aim was to critically review and synthesize the evidence from these trials. A search of the Medline database from 1966 through July 1999 was conducted to identify controlled trials designed to evaluate the efficacy of CBT in patients with somatization or symptom syndromes. A total of 31 controlled trials (29 randomized and 2 nonrandomized) were identified. Twenty-five studies targeted a specific syndrome (e.g. chronic fatigue, irritable bowel, pain) while 6 focused on more general somatization or hypochondriasis. Primary outcome assessment included physical symptoms, psychological distress and functional status in 28, 26 and 19 studies, respectively. Physical symptoms appeared the most responsive: CBT-treated patients improved more than control subjects in 71% of the studies and showed possibly greater improvement (i.e., a trend) in another 11% of the studies. A definite or possible advantage of CBT for reducing psychological distress was demonstrated in only 38 and 8% of studies, and for improving functional status in 47 and 26%. Group therapy and interventions as brief as 5 sessions proved efficacious. Benefits were sustained for up to 12 months. CBT can be an effective treatment for patients with somatization or symptom syndromes. Benefits can occur whether or not psychological distress is ameliorated. Since chronic symptoms are exceptionally common and most studies were conducted in referral populations, the optimal sequencing of CBT in treating primary care patients and the identification of those most likely to accept and respond to therapy should be further evaluated. Copyright 2000 S. Karger AG, Basel.

Economic Evaluations of Pharmaceuticals Granted a Marketing Authorisation Without the Results of Randomised Trials: A Systematic Review and Taxonomy.

PubMed

Hatswell, Anthony J; Freemantle, Nick; Baio, Gianluca

2017-02-01

Pharmaceuticals are usually granted a marketing authorisation on the basis of randomised controlled trials (RCTs). Occasionally the efficacy of a treatment is assessed without a randomised comparator group (either active or placebo). To identify and develop a taxonomic account of economic modelling approaches for pharmaceuticals licensed without RCT data. We searched PubMed, the websites of UK health technology assessment bodies and the International Society for Pharmacoeconomics and Outcomes Research Scientific Presentations Database for assessments of treatments granted a marketing authorisation by the US Food and Drug Administration or European Medicines Agency from January 1999 to May 2014 without RCT data (74 indications). The outcome of interest was the approach to modelling efficacy data. Fifty-one unique models were identified in 29 peer-reviewed articles, 30 health technology appraisals, and 15 International Society for Pharmacoeconomics and Outcomes Research abstracts concerning 30 indications (44 indications had not been modelled). We noted the high rate of non-submission to health technology assessment agencies (28/98). The majority of models (43/51) were based on 'historical controls'-comparisons to previous meta-analysis or pooling of trials (5), individual trials (16), registries/case series (15), or expert opinion (7). Other approaches used the patient as their own control, performed threshold analysis, assumed time on treatment was added to overall survival, or performed cost-minimisation analysis. There is considerable variation in the quality and approach of models constructed for drugs granted a marketing authorisation without a RCT. The most common approach is of a naive comparison to historical data (using other trials/registry data as a control group), which has considerable scope for bias.

Guideline harmonization and implementation plan for the BETTER trial: Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Family Practice

PubMed Central

Rogers, Jess; Manca, Donna; Lang-Robertson, Kelly; Bell, Stephanie; Salvalaggio, Ginetta; Greiver, Michelle; Korownyk, Christina; Klein, Doug; Carroll, June C.; Kahan, Mel; Meuser, Jamie; Buchman, Sandy; Barrett, Rebekah M.; Grunfeld, Eva

2014-01-01

Background The aim of the Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Family Practice (BETTER) randomized controlled trial is to improve the primary prevention of and screening for multiple conditions (diabetes, cardiovascular disease, cancer) and some of the associated lifestyle factors (tobacco use, alcohol overuse, poor nutrition, physical inactivity). In this article, we describe how we harmonized the evidence-based clinical practice guideline recommendations and patient tools to determine the content for the BETTER trial. Methods We identified clinical practice guidelines and tools through a structured literature search; we included both indexed and grey literature. From these guidelines, recommendations were extracted and integrated into knowledge products and outcome measures for use in the BETTER trial. End-users (family physicians, nurse practitioners, nurses and dieticians) were engaged in reviewing the recommendations and tools, as well as tailoring the content to the needs of the BETTER trial and family practice. Results In total, 3–5 high-quality guidelines were identified for each condition; from these, we identified high-grade recommendations for the prevention of and screening for chronic disease. The guideline recommendations were limited by conflicting recommendations, vague wording and different taxonomies for strength of recommendation. There was a lack of quality evidence for manoeuvres to improve the uptake of guidelines among patients with depression. We developed the BETTER clinical algorithms for the implementation plan. Although it was difficult to identify high-quality tools, 180 tools of interest were identified. Interpretation The intervention for the BETTER trial was built by integrating existing guidelines and tools, and working with end-users throughout the process to increase the intervention’s utility for practice. Trial registration: ISRCTN07170460 PMID:25077119

Interventions for promoting smoke alarm ownership and function.

PubMed

DiGuiseppi, C; Higgins, J P

2001-01-01

Residential fires caused at least 67 deaths and 2,500 non-fatal injuries to children aged 0-16 in the United Kingdom in 1998. Smoke alarm ownership is associated with a reduced risk of residential fire death. We evaluated interventions to promote residential smoke alarms, to assess their effect on smoke alarm ownership, smoke alarm function, fires and burns and other fire-related injuries. We searched the Cochrane Controlled Trials Register, Cochrane Injuries Group database, MEDLINE, EMBASE, PsycLIT, CINAHL, ERIC, Dissertation Abstracts, International Bibliography of Social Sciences, ISTP, FIREDOC and LRC. Conference proceedings, published case studies, and bibliographies were systematically searched, and investigators and relevant organisations were contacted, to identify trials. Randomised, quasi-randomised or nonrandomised controlled trials completed or published after 1969 evaluating an intervention to promote residential smoke alarms. Two reviewers independently extracted data and assessed trial quality. We identified 26 trials, of which 13 were randomised. Overall, counselling and educational interventions had only a modest effect on the likelihood of owning an alarm (OR=1.26; 95% CI: 0.87 to 1.82) or having a functional alarm (OR=1.19; 0.85 to 1.66). Counselling as part of primary care child health surveillance had greater effects on ownership (OR=1.96; 1.03 to 3.72) and function (OR=1.72; 0.78 to 3.80). Results were sensitive to trial quality, however, and effects on fire-related injuries were not reported. In two non randomised trials, direct provision of free alarms significantly increased functioning alarms and reduced fire-related injuries. Media and community education showed little benefit in non randomised trials. Counselling as part of child health surveillance may increase smoke alarm ownership and function, but its effects on injuries are unevaluated. Community smoke alarm give-away programmes apparently reduce fire-related injuries, but these trials were not randomised and results must be interpreted cautiously. Further efforts to promote smoke alarms in primary care or through give-away programmes should be evaluated by adequately designed randomised controlled trials measuring injury outcomes.

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.

Core journals that publish clinical trials of physical therapy interventions.

PubMed

Costa, Leonardo Oliveira Pena; Moseley, Anne M; Sherrington, Catherine; Maher, Christopher G; Herbert, Robert D; Elkins, Mark R

2010-11-01

The objective of this study was to identify core journals in physical therapy by identifying those that publish the most randomized controlled trials of physical therapy interventions, provide the highest-quality reports of randomized controlled trials, and have the highest journal impact factors. This study was an audit of a bibliographic database. All trials indexed in the Physiotherapy Evidence Database (PEDro) were analyzed. Journals that had published at least 80 trials were selected. The journals were ranked in 4 ways: number of trials published; mean total PEDro score of the trials published in the journal, regardless of publication year; mean total PEDro score of the trials published in the journal from 2000 to 2009; and 2008 journal impact factor. The top 5 core journals in physical therapy, ranked by the total number of trials published, were Archives of Physical Medicine and Rehabilitation, Clinical Rehabilitation, Spine, British Medical Journal (BMJ), and Chest. When the mean total PEDro score was used as the ranking criterion, the top 5 journals were Journal of Physiotherapy, Journal of the American Medical Association (JAMA), Stroke, Spine, and Clinical Rehabilitation. When the mean total PEDro score of the trials published from 2000 to 2009 was used as the ranking criterion, the top 5 journals were Journal of Physiotherapy, JAMA, Lancet, BMJ, and Pain. The most highly ranked physical therapy-specific journals were Physical Therapy (ranked eighth on the basis of the number of trials published) and Journal of Physiotherapy (ranked first on the basis of the quality of trials). Finally, when the 2008 impact factor was used for ranking, the top 5 journals were JAMA, Lancet, BMJ, American Journal of Respiratory and Critical Care Medicine, and Thorax. There were no significant relationships among the rankings on the basis of trial quality, number of trials, or journal impact factor. Physical therapists who are trying to keep up-to-date by reading the best available evidence on the effects of physical therapy interventions have to read more broadly than just physical therapy-specific journals. Readers of articles on physical therapy trials should be aware that high-quality trials are not necessarily published in journals with high impact factors.

Statistical analyses in Swedish randomised trials on mammography screening and in other randomised trials on cancer screening: a systematic review

PubMed Central

Boniol, Mathieu; Smans, Michel; Sullivan, Richard; Boyle, Peter

2015-01-01

Objectives We compared calculations of relative risks of cancer death in Swedish mammography trials and in other cancer screening trials. Participants Men and women from 30 to 74 years of age. Setting Randomised trials on cancer screening. Design For each trial, we identified the intervention period, when screening was offered to screening groups and not to control groups, and the post-intervention period, when screening (or absence of screening) was the same in screening and control groups. We then examined which cancer deaths had been used for the computation of relative risk of cancer death. Main outcome measures Relative risk of cancer death. Results In 17 non-breast screening trials, deaths due to cancers diagnosed during the intervention and post-intervention periods were used for relative risk calculations. In the five Swedish trials, relative risk calculations used deaths due to breast cancers found during intervention periods, but deaths due to breast cancer found at first screening of control groups were added to these groups. After reallocation of the added breast cancer deaths to post-intervention periods of control groups, relative risks of 0.86 (0.76; 0.97) were obtained for cancers found during intervention periods and 0.83 (0.71; 0.97) for cancers found during post-intervention periods, indicating constant reduction in the risk of breast cancer death during follow-up, irrespective of screening. Conclusions The use of unconventional statistical methods in Swedish trials has led to overestimation of risk reduction in breast cancer death attributable to mammography screening. The constant risk reduction observed in screening groups was probably due to the trial design that optimised awareness and medical management of women allocated to screening groups. PMID:26152677

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.

Screening versus routine practice in detection of atrial fibrillation in patients aged 65 or over: cluster randomised controlled trial

PubMed Central

Fitzmaurice, David A; Jowett, Sue; Mant, Jonathon; Murray, Ellen T; Holder, Roger; Raftery, J P; Bryan, S; Davies, Michael; Lip, Gregory Y H; Allan, T F

2007-01-01

Objectives To assess whether screening improves the detection of atrial fibrillation (cluster randomisation) and to compare systematic and opportunistic screening. Design Multicentred cluster randomised controlled trial, with subsidiary trial embedded within the intervention arm. Setting 50 primary care centres in England, with further individual randomisation of patients in the intervention practices. Participants 14 802 patients aged 65 or over in 25 intervention and 25 control practices. Interventions Patients in intervention practices were randomly allocated to systematic screening (invitation for electrocardiography) or opportunistic screening (pulse taking and invitation for electrocardiography if the pulse was irregular). Screening took place over 12 months in each practice from October 2001 to February 2003. No active screening took place in control practices. Main outcome measure Newly identified atrial fibrillation. Results The detection rate of new cases of atrial fibrillation was 1.63% a year in the intervention practices and 1.04% in control practices (difference 0.59%, 95% confidence interval 0.20% to 0.98%). Systematic and opportunistic screening detected similar numbers of new cases (1.62% v 1.64%, difference 0.02%, −0.5% to 0.5%). Conclusion Active screening for atrial fibrillation detects additional cases over current practice. The preferred method of screening in patients aged 65 or over in primary care is opportunistic pulse taking with follow-up electrocardiography. Trial registration Current Controlled Trials ISRCTN19633732. PMID:17673732

A community-based randomized controlled trial of Mom Power parenting intervention for mothers with interpersonal trauma histories and their young children.

PubMed

Rosenblum, Katherine L; Muzik, Maria; Morelen, Diana M; Alfafara, Emily A; Miller, Nicole M; Waddell, Rachel M; Schuster, Melisa M; Ribaudo, Julie

2017-10-01

We conducted a study to evaluate the effectiveness of Mom Power, a multifamily parenting intervention to improve mental health and parenting among high-risk mothers with young children in a community-based randomized controlled trial (CB-RCT) design. Participants (N = 122) were high-risk mothers (e.g., interpersonal trauma histories, mental health problems, poverty) and their young children (age <6 years), randomized either to Mom Power, a parenting intervention (treatment condition), or weekly mailings of parenting information (control condition). In this study, the 13-session intervention was delivered by community clinicians trained to fidelity. Pre- and post-trial assessments included mothers' mental health symptoms, parenting stress and helplessness, and connection to care. Mom Power was delivered in the community with fidelity and had good uptake (>65%) despite the risk nature of the sample. Overall, we found improvements in mental health and parenting stress for Mom Power participants but not for controls; in contrast, control mothers increased in parent-child role reversal across the trial period. The benefits of Mom Power treatment (vs. control) were accentuated for mothers with interpersonal trauma histories. Results of this CB-RCT confirm the effectiveness of Mom Power for improving mental health and parenting outcomes for high-risk, trauma-exposed women with young children. ClinicalTrials.gov Identifier: NCT01554215.

Pharmacological interventions for pain in children and adolescents with life-limiting conditions.

PubMed

Beecham, Emma; Candy, Bridget; Howard, Richard; McCulloch, Renée; Laddie, Jo; Rees, Henrietta; Vickerstaff, Victoria; Bluebond-Langner, Myra; Jones, Louise

2015-03-13

Pain is one of the most common symptoms in children and young people (CYP) with life-limiting conditions (LLCs) which include a wide range of diagnoses including cancer. The current literature indicates that pain is not well managed, however the evidence base to guide clinicians is limited. There is a clear need for evidence from a systematic review to inform prescribing. To evaluate the evidence on the effectiveness of different pharmacological interventions used for pain in CYP with LLCs. The following electronic databases were searched up to December 2014: CENTRAL (in the Cochrane Library), MEDLINE, EMBASE, PsycINFO and CINAHL. In addition, we searched conference proceedings and reference lists of included studies. For completeness, we also contacted experts in the field. No language restrictions were applied. Randomised controlled trials (RCTs), quasi-randomised studies and other studies that included a clearly defined comparator group were included. The studies investigated pharmacological treatments for pain associated with LLCs in CYP. The treatment included those specifically developed to treat pain and those that acted as an adjuvant, where the treatment was not primarily developed to treat pain but has pain relieving properties. The LLC was identified by its inclusion in the Richard Hain Directory of LLCs. Citations were screened by five review authors. Data were extracted by one review author and checked by a second. Two review authors assessed the risk of bias of included studies. A sufficient number of studies using homogeneous outcomes was not identified so a meta-analysis was not possible. We identified 24,704 citations from our database search. Nine trials with 379 participants fulfilled our inclusion criteria. Participants had cerebral palsy (CP) in five of the studies and osteogenesis imperfecta (OI) in the other four. Participants across the trials ranged in age from 2 to 19 years. All studies, apart from one cross-over trial, were parallel designed RCTs. Three of the trials on CP evaluated intrathecal baclofen (ITB) and two botulinum toxin A (BoNT-A). All of the OI trials evaluated the use of bisphosphonates (two alendronate and one pamidronate). No trials were identified that evaluated a commonly used analgesic in this patient group. Pain was a secondary outcome in five of the eight identified studies. Overall the quality of the trials was mixed. Only one study involved over 100 participants.For the two ITB studies for pain in CP, in the same study population but assessed at different time points in their disease, both found an effect on pain favouring the intervention compared to the control group (standard care or placebo) (mean difference (MD) 4.20, 95% confidence interval (CI) 2.15 to 6.25; MD 26.60, 95% CI 2.61 to 50.59, respectively). In these studies most of the adverse events related to the procedure or device for administration rather than the drug, such as swelling at the pump site. In one trial there were also eight serious adverse effects; these included difficulty swallowing and an epileptic seizure. The trial did not state if these occurred in the intervention group. At follow-up in both BoNT-A trials there was no evidence of a difference in pain between the trial arms among CP participants. The adverse events in the BoNT-A trials mostly involved those who received the intervention drug and involved seizures. Gastrointestinal problems were the most frequent adverse event in those who received alendronate. The trial investigating pamidronate found no evidence of a difference in pain compared to the control group. No adverse events were reported in this trial. Published, controlled evidence on the pharmacological interventions for pain in CYP with LLCs is limited. The evidence that is currently available evaluated pain largely as a secondary outcome and the drugs used were all adjuvants and not always commonly used in general paediatric palliative care for pain. Based on current data this systematic review is unable to determine the effects of pharmacological interventions for pain for CYP with LLCs. Future trials with larger populations should examine the effects of the drugs commonly used as analgesics; with the rising prevalence of many LLCs this becomes more necessary.

Using a drug facts box to communicate drug benefits and harms: two randomized trials.

PubMed

Schwartz, Lisa M; Woloshin, Steven; Welch, H Gilbert

2009-04-21

Direct-to-consumer prescription drug ads typically fail to provide fundamental information that consumers need to make informed decisions: data on how well the drug works. To see whether providing consumers with a drug facts box-a table quantifying outcomes with and without the drug-improves knowledge and affects judgments about prescription medications. Two randomized, controlled trials conducted between October 2006 and April 2007: a symptom drug box trial using direct-to-consumer ads for a histamine-2 blocker and a proton-pump inhibitor to treat heartburn, and a prevention drug box trial using direct-to-consumer ads for a statin and clopidogrel to prevent cardiovascular events. National sample of U.S. adults identified by random-digit dialing. Adults age 35 to 70 years who completed a mailed survey; the final samples comprised 231 participants with completed surveys in the symptom drug box trial (49% response rate) and 219 in the prevention drug box trial (46% response rate). In both trials, the control group received 2 actual drug ads (including both the front page and brief summary). The drug box group received the same ads, except that the brief summary was replaced by a drug facts box. Choice between drugs (primary outcome of the symptom drug box trial) and accurate perceptions of drug benefits and side effects (primary outcome of the prevention drug box trial). In the symptom drug box trial, 70% of the drug box group and 8% of the control group correctly identified the PPI as being "a lot more effective" than the histamine-2 blocker (P < 0.001), and 80% and 38% correctly recognized that the side effects of the 2 drugs were similar (P < 0.001). When asked what they would do if they had bothersome heartburn and could have either drug for free, 68% of the drug box group and 31% of the control group chose the proton-pump inhibitor, the superior drug (P < 0.001). In the prevention drug box trial, the drug box improved consumers' knowledge of the benefits and side effects of a statin and clopidogrel. For example, 72% of the drug box group and 9% of the control group correctly quantified the benefit (absolute risk reduction) of the statin (P < 0.001). Most of the control participants overestimated this benefit, and 65% did so by a factor of 10 or more. The trials tested drug boxes in only 4 direct-to-consumer ads. If other direct-to-consumer ads were to communicate outcome data better, the effect of the drug box would be reduced. A drug facts box improved U.S. consumers' knowledge of prescription drug benefits and side effects. It resulted in better choices between drugs for current symptoms and corrected the overestimation of benefit in the setting of prevention. National Cancer Institute and Attorney General Consumer and Prescriber Education Program.

The effect of referral for genetic counseling on genetic testing and surgical prevention in women at high risk for ovarian cancer: Results from a randomized controlled trial.

PubMed

Drescher, Charles W; Beatty, J David; Resta, Robert; Andersen, M Robyn; Watabayashi, Kate; Thorpe, Jason; Hawley, Sarah; Purkey, Hannah; Chubak, Jessica; Hanson, Nancy; Buist, Diana S M; Urban, Nicole

2016-07-22

Guidelines recommend genetic counseling and testing for women who have a pedigree suggestive of an inherited susceptibility for ovarian cancer. The authors evaluated the effect of referral to genetic counseling on genetic testing and prophylactic oophorectomy in a randomized controlled trial. Data from an electronic mammography reporting system identified 12,919 women with a pedigree that included breast cancer, of whom 625 were identified who had a high risk for inherited susceptibility to ovarian cancer using a risk-assessment questionnaire. Of these, 458 women provided informed consent and were randomized 1:1 to intervention consisting of a genetic counseling referral (n = 228) or standard clinical care (n = 230). Participants were predominantly aged 45 to 65 years, and 30% and 20% reported a personal history of breast cancer or a family history of ovarian cancer, respectively. Eighty-five percent of women in the intervention group participated in a genetic counseling session. Genetic testing was reported by 74 (33%) and 20 (9%) women in the intervention and control arms (P < .005), respectively. Five women in the intervention arm and 2 in the control arm were identified as germline mutation carriers. Ten women in the intervention arm and 3 in the control arm underwent prophylactic bilateral salpingo-oophorectomy (P < .05). Routine referral of women at high risk for ovarian cancer to genetic counseling promotes genetic testing and prophylactic surgery. The findings from the current randomized controlled trial demonstrate the value of implementing strategies that target women at high risk for ovarian cancer to ensure they are offered access to recommended care. CA Cancer J Clin 2016. © 2016 American Cancer Society, Inc. © 2016 American Cancer Society.

Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials.

PubMed

Krebs, Teri S; Johansen, Pål-Ørjan

2012-07-01

Assessments of lysergic acid diethylamide (LSD) in the treatment of alcoholism have not been based on quantitative meta-analysis. Hence, we performed a meta-analysis of randomized controlled trials in order to evaluate the clinical efficacy of LSD in the treatment of alcoholism. Two reviewers independently extracted the data, pooling the effects using odds ratios (ORs) by a generic inverse variance, random effects model. We identified six eligible trials, including 536 participants. There was evidence for a beneficial effect of LSD on alcohol misuse (OR, 1.96; 95% CI, 1.36-2.84; p = 0.0003). Between-trial heterogeneity for the treatment effects was negligible (I² = 0%). Secondary outcomes, risk of bias and limitations are discussed. A single dose of LSD, in the context of various alcoholism treatment programs, is associated with a decrease in alcohol misuse.

Endoscopic vs. Surgical Interventions for Painful Chronic Pancreatitis: What is Needed for Future Clinical Trials

PubMed Central

Windsor, John A; Reddy, Nageshwar D

2017-01-01

The treatment of painful chronic pancreatitis remains controversial. The available evidence from two randomized controlled trials favor surgical intervention, whereas an endotherapy-first approach is widely practiced. Chronic pancreatitis is complex disease with different genetic and environmental factors, different pain mechanisms and different treatment modalities including medical, endoscopic, and surgical. The widely practiced step-up approach remains unproven. In designing future clinical trials there are some important pre-requisites including a more comprehensive pain assessment tool, the optimization of conservative medical treatment and interventional techniques. Consideration should be given to the need of a control arm and the optimal timing of intervention. Pending better designed studies, the practical way forward is to identify subgroups of patients who clearly warrant endotherapy or surgery first, and to design the future clinical trials for the remainder. PMID:28079861

The design and methodology of premature ejaculation interventional studies

PubMed Central

2016-01-01

Large well-designed clinical efficacy and safety randomized clinical trials (RCTs) are required to achieve regulatory approval of new drug treatments. The objective of this article is to make recommendations for the criteria for defining and selecting the clinical trial study population, design and efficacy outcomes measures which comprise ideal premature ejaculation (PE) interventional trial methodology. Data on clinical trial design, epidemiology, definitions, dimensions and psychological impact of PE was reviewed, critiqued and incorporated into a series of recommendations for standardisation of PE clinical trial design, outcome measures and reporting using the principles of evidence based medicine. Data from PE interventional studies are only reliable, interpretable and capable of being generalised to patients with PE, when study populations are defined by the International Society for Sexual Medicine (ISSM) multivariate definition of PE. PE intervention trials should employ a double-blind RCT methodology and include placebo control, active standard drug control, and/or dose comparison trials. Ejaculatory latency time (ELT) and subject/partner outcome measures of control, personal/partner/relationship distress and other study-specific outcome measures should be used as outcome measures. There is currently no published literature which identifies a clinically significant threshold response to intervention. The ISSM definition of PE reflects the contemporary understanding of PE and represents the state-of-the-art multi-dimensional definition of PE and is recommended as the basis of diagnosis of PE for all PE clinical trials. PMID:27652224

Chemotherapy and targeted therapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials.

PubMed

Eckel, Florian; Schmid, Roland M

2014-01-01

In biliary tract cancer, gemcitabine platinum (GP) doublet palliative chemotherapy is the current standard treatment. The aim of this study was to analyze recent trials, even those small and nonrandomized, and identify superior new regimens. Trials published in English between January 2000 and January 2014 were analyzed, as well as ASCO abstracts from 2010 to 2013. In total, 161 trials comprising 6,337 patients were analyzed. The pooled results of standard therapy GP (no fluoropyrimidine, F, or other drug) were as follows: the median response rate (RR), tumor control rate (TCR), time to tumor progression (TTP) and overall survival (OS) were 25.9 and 63.5%, and 5.3 and 9.5 months, respectively. GFP triplets as well as G-based chemotherapy plus targeted therapy were significantly superior to GP concerning tumor control (TCR, TTP) and OS, with no difference in RR. Triplet combinations of GFP as well as G-based chemotherapy with (predominantly EGFR) targeted therapy are most effective concerning tumor control and survival.

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.

Safety monitoring of ophthalmic biologics: a systematic review of pre- and postmarketing safety data.

PubMed

Penedones, Ana; Mendes, Diogo; Alves, Carlos; Batel Marques, Francisco

2014-11-01

The present study evaluates the safety of the biologics approved for the treatment of ocular diseases. The European medicines agency Website was searched to identify biologics with approved ophthalmologic therapeutic indications. A systematic search was performed using MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) and the International Clinical Trials Registry Platform up to December 2013. Pre-marketing, phase III randomized controlled trials (RCT), postmarketing clinical trials, observational longitudinal studies, and case reports involving adverse events (AE) were included. Methodological quality was assessed by Downs & Black checklist. All European spontaneous reports of AE included in the Eudravigilance up to December 2013 were also considered. AE were classified as ocular (related and non-related with the injection procedure) and non-ocular (related or non-related with vascular endothelial growth factor inhibition). Incidences of all reported AEs were estimated. Pegaptanib, ranibizumab, and aflibercept were identified as ophthalmic biologics. Fourteen premarketing RCT, 7 postmarketing clinical trials, 31 observational studies, along with 31 case reports and 7,720 spontaneous reports were identified and included in this study. Both in pre- and postmarketing settings, ocular AEs were more frequent than non-ocular AEs. Premarketing safety data inform the most common AEs. Postmarketing studies suggest an increased number of events such as retinal pigmented epithelium tears (0.6%-24%), thromboembolic events (0.8%-5%), and mortality (2.8%-4%). This study highlights the need to properly evaluate the risk for rare, serious, and long-term AEs, such as thromboembolic events, since they can lead to imbalances in the benefit-risk ratio of biologics in ophthalmology.

Methodological quality of randomised controlled trials in burns care. A systematic review.

PubMed

Danilla, Stefan; Wasiak, Jason; Searle, Susana; Arriagada, Cristian; Pedreros, Cesar; Cleland, Heather; Spinks, Anneliese

2009-11-01

To evaluate the methodological quality of published randomised controlled trials (RCTs) in burn care treatment and management. Using a predetermined search strategy we searched Ovid MEDLINE (1950 to January 2008) database to identify all English RCTs related to burn care. Full text studies identified were reviewed for key demographic and methodological characteristics. Methodological trial quality was assessed using the Jadad scale. A total of 257 studies involving 14,535 patients met the inclusion criteria. The median Jadad score was 2 (out of a best possible score of 5). Information was given in the introduction and discussion sections of most RCTs, although insufficient detail was provided on randomisation, allocation concealment, and blinding. The number of RCTs increased between 1950 and 2008 (Spearman's rho=0.6129, P<0.001), although the reporting quality did not improve over the same time period (P=0.1896) and was better in RCTs with larger sample sizes (median Jadad score, 4 vs. 2 points, P<0.0001). Methodological quality did not correlate with journal impact factor (P=0.2371). The reporting standards of RCTs are highly variable and less than optimal in most cases. The advent of evidence-based medicine heralds a new approach to burns care and systematic steps are needed to improve the quality of RCTs in this field. Identifying and reviewing the existing number of RCTs not only highlights the need for burn clinicians to conduct more trials, but may also encourage burn health clinicians to consider the importance of conducting trials that follow appropriate, evidence-based standards.

Need for common internal controls when assessing the relative efficacy of pharmacologic agents using a meta-analytic approach: case study of cyclooxygenase 2-selective inhibitors for the treatment of osteoarthritis.

PubMed

Lee, Chin; Hunsche, Elke; Balshaw, Robert; Kong, Sheldon X; Schnitzer, Thomas J

2005-08-15

To evaluate the role of common internal controls in a meta-analysis of the relative efficacy of cyclooxygenase 2-selective inhibitors (coxibs) in the treatment of osteoarthritis (OA). A systematic search of Medline and US Food and Drug Administration electronic databases was performed to identify randomized, placebo-controlled clinical trials of coxibs (etoricoxib, celecoxib, rofecoxib, valdecoxib) in patients with hip and/or knee OA. The effect size for coxibs and common active internal controls (nonsteroidal antiinflammatory drugs [NSAIDs], naproxen) were determined by the mean changes from baseline in Western Ontario and McMaster Universities Osteoarthritis Index pain subscores as compared with placebo. The effect size for all coxib groups combined (0.44) indicated greater efficacy as compared with placebo, but significant heterogeneity (P < 0.0001) was observed. Rofecoxib at dosages of 12.5 mg/day and 25 mg/day and etoricoxib at a dosage of 60 mg/day had similar effect sizes (0.68 and 0.73, respectively), but these effect sizes were comparatively greater than those for both celecoxib at dosages of 200 mg/day and 100 mg twice daily or valdecoxib at a dosage of 10 mg/day (0.26 and 0.16, respectively). The effect sizes for NSAIDs or naproxen versus placebo, as determined using data from rofecoxib/etoricoxib trials, were consistently higher than the effect sizes derived from trials of celecoxib/valdecoxib. Significant heterogeneity was present in the overall effect size for NSAIDs (P = 0.007) and naproxen (P = 0.04) groups based on data available from all coxib trials. Coxibs and common active internal controls showed larger effect sizes versus placebo in the rofecoxib/etoricoxib trials than in the celecoxib/valdecoxib trials. These findings suggest systematic differences among published coxib trials and emphasize the need for direct-comparison trials. In the absence of such trials, common internal controls should be assessed when performing indirect meta-analytic comparisons.

Controlled trial of hyposensitisation in children with food-induced hyperkinetic syndrome.

PubMed

Egger, J; Stolla, A; McEwen, L M

1992-05-09

Food intolerance seems to be an important cause of the hyperkinetic syndrome, but restricted diets are expensive, socially disruptive, and often nutritionally inadequate. Enzyme-potentiated desensitisation (EPD) may overcome some of these difficulties. EPD was tested in a double-blind placebo-controlled trial among 40 children with food-induced hyperkinetic behaviour disorder. A total of 185 children with established hyperkinetic syndrome underwent oligoantigenic dietary treatment for four weeks. 116 whose behaviour responded had provoking foods identified by sequential reintroduction. Foods that reproducibly provoked overactivity were avoided. 40 patients who were then invited to take part in the hyposensitisation trial were randomly assigned to treated and control groups. Treated patients received three doses of EPD (beta-glucuronidase and small quantities of food antigens) intradermally at two-monthly intervals. Controls received buffer only. Thereafter, patients were allowed to eat known provoking foods. Of 20 patients who received active treatment, 16 became tolerant towards provoking foods compared with 4 of 20 who received placebo (p less than 0.001). Our results show that EPD permits children with food-induced hyperkinetic syndrome to eat foods that had previously been identified as responsible for their symptoms. These results also support the notion that food allergy is a possible mechanism of the hyperkinetic syndrome.

Current Evidence on Auricular Therapy for Chemotherapy-Induced Nausea and Vomiting in Cancer Patients: A Systematic Review of Randomized Controlled Trials

PubMed Central

Molassiotis, Alexander; Wang, Tao; Suen, Lorna K. P.

2014-01-01

Auricular therapy (AT) has been historically viewed as a convenient approach adjunct to pharmacological therapy for cancer patients with chemotherapy-induced nausea and vomiting (CINV). The aim of this study was to assess the evidence of the therapeutic effect of AT for CINV management in cancer patients. Relevant randomized controlled trials were retrieved from 12 electronic databases without language restrictions. Meanwhile, manual search was conducted for Chinese journals on complementary medicine published within the last five years, and the reference lists of included studies were also checked to identify any possible eligible studies. Twenty-one studies with 1713 participants were included. The effect rate of AT for managing acute CINV ranged from 44.44% to 93.33% in the intervention groups and 15% to 91.67% in the control groups. For delayed CINV, it was 62.96% to 100% and 25% to 100%, respectively. AT seems to be a promising approach in managing CINV. However, the level of evidence was low and the definite effect cannot be concluded as there were significant methodological flaws identified in the analyzed studies. The implications drawn from the 21 studies put some clues for future practice in this area including the need to conduct more rigorously designed randomized controlled trials. PMID:25525445

Differential sensory fMRI signatures in autism and schizophrenia: Analysis of amplitude and trial-to-trial variability.

PubMed

Haigh, Sarah M; Gupta, Akshat; Barb, Scott M; Glass, Summer A F; Minshew, Nancy J; Dinstein, Ilan; Heeger, David J; Eack, Shaun M; Behrmann, Marlene

2016-08-01

Autism and schizophrenia share multiple phenotypic and genotypic markers, and there is ongoing debate regarding the relationship of these two disorders. To examine whether cortical dynamics are similar across these disorders, we directly compared fMRI responses to visual, somatosensory and auditory stimuli in adults with autism (N=15), with schizophrenia (N=15), and matched controls (N=15). All participants completed a one-back letter detection task presented at fixation (to control attention) while task-irrelevant sensory stimulation was delivered to the different modalities. We focused specifically on the response amplitudes and the variability in sensory fMRI responses of the two groups, given the evidence of greater trial-to-trial variability in adults with autism. Both autism and schizophrenia individuals showed weaker signal-to-noise ratios (SNR) in sensory-evoked responses compared to controls (d>0.42), but for different reasons. For the autism group, the fMRI response amplitudes were indistinguishable from controls but were more variable trial-to-trial (d=0.47). For the schizophrenia group, response amplitudes were smaller compared to autism (d=0.44) and control groups (d=0.74), but were not significantly more variable (d<0.29). These differential group profiles suggest (1) that greater trial-to-trial variability in cortical responses may be specific to autism and is not a defining characteristic of schizophrenia, and (2) that blunted response amplitudes may be characteristic of schizophrenia. The relationship between the amplitude and the variability of cortical activity might serve as a specific signature differentiating these neurodevelopmental disorders. Identifying the neural basis of these responses and their relationship to the underlying genetic bases may substantially enlighten the understanding of both disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

Understanding the outcomes measures used in Huntington disease pharmacologicaltrials: A systematic review

PubMed Central

Carlozzi, Noelle E; Miciura, Angela; Migliore, Nicholas; Dayalu, Praveen

2014-01-01

Background The identification of the gene mutation causing Huntington disease has raised hopes for new treatments to ease symptoms and slow functional decline. As such, there has been a push towards designing efficient pharmacological trials (i.e., drug trials), especially with regard to selecting outcomes measures that are both brief and sensitive to changes across the course of the disease, from subtle prodromal changes, to more severe end-stage changes. Objectives Recently, to aid in efficient development of new HD research studies, the National Institute of Neurological Disorders and Stroke (NINDS) published recommendations for measurement selection in HD. While these recommendations are helpful, many of the recommended measures have little published data in HD. As such, we conducted a systematic review of the literature to identify the most common outcomes measures used in HD clinical trials. Methods Major medical databases, including PubMed, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials, were used to identify peer-reviewed journal articles in English from 2001 through April 2013; 151 pharmacological trials were identified. Results The majority of HD clinical trials employed clinician-reported outcomes measures (93%); patient reported outcome measures (11%) and observer reported outcome measures (3%) were used with much less frequency. Conclusions We provide a review of the most commonly used measures across these trials, compare these measures to the clinical recommendations made by the NINDS working groups, and provide recommendations for selecting measures for future clinical trials that meet the Food and Drug Administration standards. PMID:25300328

All-Wales licensed premises intervention (AWLPI): a randomised controlled trial to reduce alcohol-related violence

PubMed Central

2014-01-01

Background Alcohol-related violence in and in the vicinity of licensed premises continues to place a considerable burden on the United Kingdom’s (UK) health services. Robust interventions targeted at licensed premises are therefore required to reduce the costs of alcohol-related harm. Previous evaluations of interventions in licensed premises have a number of methodological limitations and none have been conducted in the UK. The aim of the trial was to determine the effectiveness of the Safety Management in Licensed Environments intervention designed to reduce alcohol-related violence in licensed premises, delivered by Environmental Health Officers, under their statutory authority to intervene in cases of violence in the workplace. Methods/Design A national randomised controlled trial, with licensed premises as the unit of allocation. Premises were identified from all 22 Local Authorities in Wales. Eligible premises were those with identifiable violent incidents on premises, using police recorded violence data. Premises were allocated to intervention or control by optimally balancing by Environmental Health Officer capacity in each Local Authority, number of violent incidents in the 12 months leading up to the start of the project and opening hours. The primary outcome measure is the difference in frequency of violence between intervention and control premises over a 12 month follow-up period, based on a recurrent event model. The trial incorporates an embedded process evaluation to assess intervention implementation, fidelity, reach and reception, and to interpret outcome effects, as well as investigate its economic impact. Discussion The results of the trial will be applicable to all statutory authorities directly involved with managing violence in the night time economy and will provide the first formal test of Health and Safety policy in this environment. If successful, opportunities for replication and generalisation will be considered. Trial registration UKCRN 14077; ISRCTN78924818. PMID:24405575

Poor uptake of an online intervention in a cluster randomised controlled trial of online diabetes education for rural general practitioners.

PubMed

Paul, Christine L; Piterman, Leon; Shaw, Jonathan E; Kirby, Catherine; Forshaw, Kristy L; Robinson, Jennifer; Thepwongsa, Isaraporn; Sanson-Fisher, Robert W

2017-03-23

In Australia, rural and remote communities have high rates of diabetes-related death and hospitalisation. General practitioners (GPs) play a major role in diabetes detection and management. Education of GPs could optimise diabetes management and improve patient outcomes at a population level. The study aimed to describe the uptake of a continuing medical education intervention for rural GPs and its impact on the viability of a cluster randomised controlled trial of the effects of continuing medical education on whole-town diabetes monitoring and control. Trial design: the cluster randomised controlled trial involved towns as the unit of allocation and analysis with outcomes assessed by de-identified pathology data (not reported here). The intervention programme consisted of an online active learning module, direct electronic access to specialist advice and performance feedback. Multiple rounds of invitation were used to engage GPs with the online intervention content. Evidence-based strategies (e.g. pre-notification, rewards, incentives) were incorporated into the invitations to enrol in the programme. Recruitment to the programme was electronically monitored through the hosting software package during the study intervention period. Eleven matched pairs of towns were included in the study. There were 146 GPs in the 11 intervention towns, of whom 34 (23.3%) enrolled in the programme, and 8 (5.5%) completed the online learning module. No town had more than 10% of the resident GPs complete the learning module. There were no contacts made by GPs regarding requests for specialist advice. Consequently, the trial was discontinued. There is an ongoing need to engage primary care physicians in improving diabetes monitoring and management in rural areas. Online training options, while notionally attractive and accessible, are not likely to have high levels of uptake, even when evidence-based recruitment strategies are implemented. Australian New Zealand Clinical Trials Registry, identifier: ACTRN12611000553976 . Retrospectively registered on 31 May 2011.

Bilingualism influences inhibitory control in auditory comprehension

PubMed Central

Blumenfeld, Henrike K.; Marian, Viorica

2013-01-01

Bilinguals have been shown to outperform monolinguals at suppressing task-irrelevant information. The present study aimed to identify how processing linguistic ambiguity during auditory comprehension may be associated with inhibitory control. Monolinguals and bilinguals listened to words in their native language (English) and identified them among four pictures while their eye-movements were tracked. Each target picture (e.g., hamper) appeared together with a similar-sounding within-language competitor picture (e.g., hammer) and two neutral pictures. Following each eye-tracking trial, priming probe trials indexed residual activation of target words, and residual inhibition of competitor words. Eye-tracking showed similar within-language competition across groups; priming showed stronger competitor inhibition in monolinguals than in bilinguals, suggesting differences in how inhibitory control was used to resolve within-language competition. Notably, correlation analyses revealed that inhibition performance on a nonlinguistic Stroop task was related to linguistic competition resolution in bilinguals but not in monolinguals. Together, monolingual-bilingual comparisons suggest that cognitive control mechanisms can be shaped by linguistic experience. PMID:21159332

Selecting promising treatments in randomized Phase II cancer trials with an active control.

PubMed

Cheung, Ying Kuen

2009-01-01

The primary objective of Phase II cancer trials is to evaluate the potential efficacy of a new regimen in terms of its antitumor activity in a given type of cancer. Due to advances in oncology therapeutics and heterogeneity in the patient population, such evaluation can be interpreted objectively only in the presence of a prospective control group of an active standard treatment. This paper deals with the design problem of Phase II selection trials in which several experimental regimens are compared to an active control, with an objective to identify an experimental arm that is more effective than the control or to declare futility if no such treatment exists. Conducting a multi-arm randomized selection trial is a useful strategy to prioritize experimental treatments for further testing when many candidates are available, but the sample size required in such a trial with an active control could raise feasibility concerns. In this study, we extend the sequential probability ratio test for normal observations to the multi-arm selection setting. The proposed methods, allowing frequent interim monitoring, offer high likelihood of early trial termination, and as such enhance enrollment feasibility. The termination and selection criteria have closed form solutions and are easy to compute with respect to any given set of error constraints. The proposed methods are applied to design a selection trial in which combinations of sorafenib and erlotinib are compared to a control group in patients with non-small-cell lung cancer using a continuous endpoint of change in tumor size. The operating characteristics of the proposed methods are compared to that of a single-stage design via simulations: The sample size requirement is reduced substantially and is feasible at an early stage of drug development.

Standard care versus protocol based therapy for new onset Pseudomonas aeruginosa in cystic fibrosis.

PubMed

Mayer-Hamblett, Nicole; Rosenfeld, Margaret; Treggiari, Miriam M; Konstan, Michael W; Retsch-Bogart, George; Morgan, Wayne; Wagener, Jeff; Gibson, Ronald L; Khan, Umer; Emerson, Julia; Thompson, Valeria; Elkin, Eric P; Ramsey, Bonnie W

2013-10-01

The Early Pseudomonal Infection Control (EPIC) randomized trial rigorously evaluated the efficacy of different antibiotic regimens for eradication of newly identified Pseudomonas (Pa) in children with cystic fibrosis (CF). Protocol based therapy in the trial was provided based on culture positivity independent of symptoms. It is unclear whether outcomes observed in the clinical trial were different than those that would have been observed with historical standard of care driven more heavily by respiratory symptoms than culture positivity alone. We hypothesized that the incidence of Pa recurrence and hospitalizations would be significantly reduced among trial participants as compared to historical controls whose standard of care preceded the widespread adoption of tobramycin inhalation solution (TIS) as initial eradication therapy at the time of new isolation of Pa. Eligibility criteria from the trial were used to derive historical controls from the Epidemiologic Study of CF (ESCF) who received standard of care treatment from 1995 to 1998, before widespread availability of TIS. Pa recurrence and hospitalization outcomes were assessed over a 15-month time period. As compared to 100% of the 304 trial participants, only 296/608 (49%) historical controls received antibiotics within an average of 20 weeks after new onset Pa. Pa recurrence occurred among 104/298 (35%) of the trial participants as compared to 295/549 (54%) of historical controls (19% difference, 95% CI: 12%, 26%, P < 0.001). No significant differences in the incidence of hospitalization were observed between cohorts. Protocol-based antimicrobial therapy for newly acquired Pa resulted in a lower rate of Pa recurrence but comparable hospitalization rates as compared to a historical control cohort less aggressively treated with antibiotics for new onset Pa. © 2013 Wiley Periodicals, Inc.

Standard Care versus Protocol Based Therapy for New Onset Pseudomonas aeruginosa in Cystic Fibrosis

PubMed Central

Mayer-Hamblett, Nicole; Rosenfeld, Margaret; Treggiari, Miriam M.; Konstan, Michael W.; Retsch-Bogart, George; Morgan, Wayne; Wagener, Jeff; Gibson, Ronald L.; Khan, Umer; Emerson, Julia; Thompson, Valeria; Elkin, Eric P.; Ramsey, Bonnie W.

2014-01-01

Rationale The Early Pseudomonal Infection Control (EPIC) randomized trial rigorously evaluated the efficacy of different antibiotic regimens for eradication of newly identified Pseudomonas (Pa) in children with cystic fibrosis (CF). Protocol based therapy in the trial was provided based on culture positivity independent of symptoms. It is unclear whether outcomes observed in the clinical trial were different than those that would have been observed with historical standard of care driven more heavily by respiratory symptoms than culture positivity alone. We hypothesized that the incidence of Pa recurrence and hospitalizations would be significantly reduced among trial participants as compared to historical controls whose standard of care preceded the widespread adoption of tobramycin inhalation solution (TIS) as initial eradication therapy at the time of new isolation of Pa. Methods Eligibility criteria from the trial were used to derive historical controls from the Epidemiologic Study of CF (ESCF) who received standard of care treatment from 1995 to 1998, before widespread availability of TIS. Pa recurrence and hospitalization outcomes were assessed over a 15-month time period. Results As compared to 100% of the 304 trial participants, only 296/608 (49%) historical controls received antibiotics within an average of 20 weeks after new onset Pa. Pa recurrence occurred among 104/298 (35%) of the trial participants as compared to 295/549 (54%) of historical controls (19% difference, 95% CI: 12%, 26%, p<0.001). No significant differences in the incidence of hospitalization were observed between cohorts. Conclusions Protocol-based antimicrobial therapy for newly acquired Pa resulted in a lower rate of Pa recurrence but comparable hospitalization rates as compared to a historical control cohort less aggressively treated with antibiotics for new onset Pa. PMID:23818295

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.

Efficacy of Chinese herbal medicine for stroke modifiable risk factors: a systematic review.

PubMed

Peng, Wenbo; Lauche, Romy; Ferguson, Caleb; Frawley, Jane; Adams, Jon; Sibbritt, David

2017-01-01

The vast majority of stroke burden is attributable to its modifiable risk factors. This paper aimed to systematically summarise the evidence of Chinese herbal medicine (CHM) interventions on stroke modifiable risk factors for stroke prevention. A literature search was conducted via the MEDLINE, CINAHL/EBSCO, SCOPUS, and Cochrane Database from 1996 to 2016. Randomised controlled trials or cross-over studies were included. Risk of bias was assessed according to the Cochrane Risk of Bias tool. A total of 46 trials (6895 participants) were identified regarding the use of CHM interventions in the management of stroke risk factors, including 12 trials for hypertension, 10 trials for diabetes, eight trials for hyperlipidemia, seven trials for impaired glucose tolerance, three trials for obesity, and six trials for combined risk factors. Amongst the included trials with diverse study design, an intervention of CHM as a supplement to biomedicine and/or a lifestyle intervention was found to be more effective in lowering blood pressure, decreasing blood glucose level, helping impaired glucose tolerance reverse to normal, and/or reducing body weight compared to CHM monotherapy. While no trial reported deaths amongst the CHM groups, some papers do report moderate adverse effects associated with CHM use. However, the findings of such beneficial effects of CHM should be interpreted with caution due to the heterogeneous set of complex CHM studied, the various control interventions employed, the use of different participants' inclusion criteria, and low methodological quality across the published studies. The risk of bias of trials identified was largely unclear in the domains of selection bias and detection bias across the included studies. This study showed substantial evidence of varied CHM interventions improving the stroke modifiable risk factors. More rigorous research examining the use of CHM products for sole or multiple major stroke risk factors are warranted.

Industry sponsorship bias in research findings: a network meta-analysis of LDL cholesterol reduction in randomised trials of statins

PubMed Central

Dias, Sofia; Ades, A E

2014-01-01

Objective To explore the risk of industry sponsorship bias in a systematically identified set of placebo controlled and active comparator trials of statins. Design Systematic review and network meta-analysis. Eligibility Open label and double blind randomised controlled trials comparing one statin with another at any dose or with control (placebo, diet, or usual care) for adults with, or at risk of developing, cardiovascular disease. Only trials that lasted longer than four weeks with more than 50 participants per trial arm were included. Two investigators assessed study eligibility. Data sources Bibliographic databases and reference lists of relevant articles published between 1 January 1985 and 10 March 2013. Data extraction One investigator extracted data and another confirmed accuracy. Main outcome measure Mean absolute change from baseline concentration of low density lipoprotein (LDL) cholesterol. Data synthesis Study level outcomes from randomised trials were combined using random effects network meta-analyses. Results We included 183 randomised controlled trials of statins, 103 of which were two-armed or multi-armed active comparator trials. When all of the existing randomised evidence was synthesised in network meta-analyses, there were clear differences in the LDL cholesterol lowering effects of individual statins at different doses. In general, higher doses resulted in higher reductions in baseline LDL cholesterol levels. Of a total of 146 industry sponsored trials, 64 were placebo controlled (43.8%). The corresponding number for the non-industry sponsored trials was 16 (43.2%). Of the 35 unique comparisons available in 37 non-industry sponsored trials, 31 were also available in industry sponsored trials. There were no systematic differences in magnitude between the LDL cholesterol lowering effects of individual statins observed in industry sponsored versus non-industry sponsored trials. In industry sponsored trials, the mean change from baseline LDL cholesterol level was on average 1.77 mg/dL (95% credible interval −11.12 to 7.66) lower than the change observed in non-industry sponsored trials. There was no detectable inconsistency in the evidence network. Conclusions Our analysis shows that the findings obtained from industry sponsored statin trials seem similar in magnitude as those in non-industry sources. There are actual differences in the effectiveness of individual statins at various doses that explain previously observed discrepancies between industry and non-industry sponsored trials. PMID:25281681

Selectivity of N170 for visual words in the right hemisphere: Evidence from single-trial analysis.

PubMed

Yang, Hang; Zhao, Jing; Gaspar, Carl M; Chen, Wei; Tan, Yufei; Weng, Xuchu

2017-08-01

Neuroimaging and neuropsychological studies have identified the involvement of the right posterior region in the processing of visual words. Interestingly, in contrast, ERP studies of the N170 typically demonstrate selectivity for words more strikingly over the left hemisphere. Why is right hemisphere selectivity for words during the N170 epoch typically not observed, despite the clear involvement of this region in word processing? One possibility is that amplitude differences measured on averaged ERPs in previous studies may have been obscured by variation in peak latency across trials. This study examined this possibility by using single-trial analysis. Results show that words evoked greater single-trial N170s than control stimuli in the right hemisphere. Additionally, we observed larger trial-to-trial variability on N170 peak latency for words as compared to control stimuli over the right hemisphere. Results demonstrate that, in contrast to much of the prior literature, the N170 can be selective to words over the right hemisphere. This discrepancy is explained in terms of variability in trial-to-trial peak latency for responses to words over the right hemisphere. © 2017 Society for Psychophysiological Research.

Outcomes with individual versus group physical therapy for treating urinary incontinence and low back pain: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Robertson, Belinda; Harding, Katherine E

2014-11-01

To evaluate the existing evidence comparing the outcomes of rehabilitation conducted in a group setting and individual therapy for patients receiving rehabilitation. Electronic databases MEDLINE, CINAHL, EMBASE, PEDro, and OT Seeker were searched from the earliest date possible to July 2013. Additional references were identified by manual scanning of reference lists. Randomized controlled trials investigating the effect of group therapy compared with individual therapy for patients receiving rehabilitation were included for review. Two reviewers independently applied the inclusion and exclusion criteria to identify included articles. Initial search identified 1527 potential articles, of which 16 trials with 2337 participants were included in the final review. Data extraction was completed for all included trials by one reviewer, using a customized data extraction form. Data were checked for accuracy by a second reviewer. Trials were independently assessed by 2 reviewers for methodological quality using the PEDro scale. Trials meeting inclusion criteria had been conducted in back pain (n=6 studies), urinary incontinence (n=5), learning disability (n=2), hearing loss (n=1), joint replacement (n=1), and aphasia (n=1). Meta-analysis of physical therapy trials in back pain and urinary incontinence reporting sufficient homogeneous data showed no significant difference in outcomes for group versus individual therapy. These results were also supported by qualitative analysis of the remaining studies in these populations, but there is insufficient evidence to draw conclusions regarding other clinical areas. Evidence shows that providing rehabilitation in a group format results in equivalent clinical outcomes to provision of similar therapy in an individual format in the treatment of back pain and urinary incontinence. There is currently insufficient evidence to draw similar conclusions in other populations or fields of rehabilitation. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Birth Control in Clinical Trials: Industry Survey of Current Use Practices, Governance, and Monitoring.

PubMed

Stewart, J; Breslin, W J; Beyer, B K; Chadwick, K; De Schaepdrijver, L; Desai, M; Enright, B; Foster, W; Hui, J Y; Moffat, G J; Tornesi, B; Van Malderen, K; Wiesner, L; Chen, C L

2016-03-01

The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology Technical Committee sponsored a pharmaceutical industry survey on current industry practices for contraception use during clinical trials. The objectives of the survey were to improve our understanding of the current industry practices for contraception requirements in clinical trials, the governance processes set up to promote consistency and/or compliance with contraception requirements, and the effectiveness of current contraception practices in preventing pregnancies during clinical trials. Opportunities for improvements in current practices were also considered. The survey results from 12 pharmaceutical companies identified significant variability among companies with regard to contraception practices and governance during clinical trials. This variability was due primarily to differences in definitions, areas of scientific uncertainty or misunderstanding, and differences in company approaches to enrollment in clinical trials. The survey also revealed that few companies collected data in a manner that would allow a retrospective understanding of the reasons for failure of birth control during clinical trials. In this article, suggestions are made for topics where regulatory guidance or scientific publications could facilitate best practice. These include provisions for a pragmatic definition of women of childbearing potential, guidance on how animal data can influence the requirements for male and female birth control, evidence-based guidance on birth control and pregnancy testing regimes suitable for low- and high-risk situations, plus practical methods to ascertain the risk of drug-drug interactions with hormonal contraceptives.

Effectiveness of treatments for infantile colic: systematic review

PubMed Central

Lucassen, P L B J; Assendelft, W J J; Gubbels, J W; van Eijk, J T M; van Geldrop, W J; Neven, A Knuistingh

1998-01-01

Objective: To evaluate the effectiveness of diets, drug treatment, and behavioural interventions on infantile colic in trials with crying or the presence of colic as the primary outcome measure. Data sources: Controlled clinical trials identified by a highly sensitive search strategy in Medline (1966-96), Embase (1986-95), and the Cochrane Controlled Trials Register, in combination with reference checking for further relevant publications. Keywords were crying and colic. Study selection: Two independent assessors selected controlled trials with interventions lasting at least 3 days that included infants younger than 6 months who cried excessively. Data synthesis: Methodological quality was assessed by two assessors independently with a quality assessment scale (range 0-5). Effect sizes were calculated as percentage success. Effect sizes of trials using identical interventions were pooled using a random effects model. Results: 27 controlled trials were identified. Elimination of cows’ milk protein was effective when substituted by hypoallergenic formula milks (effect size 0.22 (95% confidence interval 0.09 to 0.34)). The effectiveness of substitution by soy formula milks was unclear when only trials of good methodological quality were considered. The benefit of eliminating cows’ milk protein was not restricted to highly selected populations. Dicyclomine was effective (effect size 0.46 ( 0.33 to 0.60)), but serious side effects have been reported. The advice to reduce stimulation was beneficial (effect size 0.48 (0.23 to 0.74)), whereas the advice to increase carrying and holding seemed not to reduce crying. No benefit was shown for simethicone. Uncertainty remained about the effectiveness of low lactose formula milks. Conclusions: Infantile colic should preferably be treated by advising carers to reduce stimulation and with a one week trial of a hypoallergenic formula milk. Key messages Infantile colic is common during the first months of life, but its cause is unknown A definite diagnosis of infantile colic should be followed by a one week trial of substituting cows’ milk with hypoallergenic formula milk Dietary intervention should be combined with behavioural interventions: general advice, reassurance, reduction in stimuli, and sensitive differential responding (teaching parents to be more appropriately responsive to their infants with less overstimulation and more effective soothing) Anticholinergic drugs are not recommended because of their serious side effects PMID:9596593

Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial.

PubMed

Bucur, Roxana C; Reid, Lauren S; Hamilton, Celeste J; Cummings, Steven R; Jamal, Sophie A

2013-09-08

Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. This will be an open-label randomized, controlled trial conducted at Women's College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the 'multiple comparisons with the best' approach for data analyses, as this strategy allows practical considerations of ease of use and tolerability to guide selection of the preparation for future studies. Data from this protocol will be used to develop a randomized, controlled trial of nitrates to prevent osteoporotic fractures. ClinicalTrials.gov Identifier: NCT01387672. Controlled-Trials.com: ISRCTN08860742.

Mind-body Therapies for Menopausal Symptoms: A Systematic Review

PubMed Central

Innes, Kim E; Selfe, Terry Kit; Vishnu, Abhishek

2010-01-01

Objective To systematically review the peer-reviewed literature regarding the effects of self-administered mind-body therapies on menopausal symptoms. Methods To identify qualifying studies, we searched 10 scientific databases and scanned bibliographies of relevant review papers and all identified articles. The methodological quality of all studies was assessed systematically using predefined criteria. Results Twenty-one papers representing 18 clinical trials from 6 countries met our inclusion criteria, including 12 randomized controlled trials (N=719), 1 non-randomized controlled trial (N=58), and 5 uncontrolled trials (N=105). Interventions included yoga and/or meditation-based programs, tai chi, and other relaxation practices, including muscle relaxation and breath-based techniques, relaxation response training, and low frequency sound-wave therapy. Eight of the nine studies of yoga, tai chi, and meditation-based programs reported improvement in overall menopausal and vasomotor symptoms; six of seven trials indicated improvement in mood and sleep with yoga-based programs, and four studies reported reduced musculoskeletal pain. Results from the remaining nine trials suggest that breath-based and other relaxation therapies also show promise for alleviating vasomotor and other menopausal symptoms, although intergroup findings were mixed. Most studies reviewed suffered methodological or other limitations, complicating interpretation of findings. Conclusions Collectively, findings of these studies suggest that yoga-based and certain other mind-body therapies may be beneficial for alleviating specific menopausal symptoms. However, the limitations characterizing most studies hinder interpretation of findings and preclude firm conclusions regarding efficacy. Additional large, methodologically sound trials are needed to determine the effects of specific mind-body therapies on menopausal symptoms, examine long-term outcomes, and investigate underlying mechanisms. PMID:20167444

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.

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.

A systematic review of training programmes for recruiters to randomised controlled trials.

PubMed

Townsend, Daisy; Mills, Nicola; Savović, Jelena; Donovan, Jenny L

2015-09-28

Recruitment to randomised controlled trials (RCTs) is often difficult. Clinician related factors have been implicated as important reasons for low rates of recruitment. Clinicians (doctors and other health professionals) can experience discomfort with some underlying principles of RCTs and experience difficulties in conveying them positively to potential trial participants. Recruiter training has been suggested to address identified problems but a synthesis of this research is lacking. The aim of our study was to systematically review the available evidence on training interventions for recruiters to randomised trials. Studies that evaluated training programmes for trial recruiters were included. Those that provided only general communication training not linked to RCT recruitment were excluded. Data extraction and quality assessment were completed by two reviewers independently, with a third author where necessary. Seventeen studies of 9615 potentially eligible titles and abstracts were included in the review: three randomised controlled studies, two non-randomised controlled studies, nine uncontrolled pre-test/post-test studies, two qualitative studies, and a post-training questionnaire survey. Most studies were of moderate or weak quality. Training programmes were mostly set within cancer trials, and usually consisted of workshops with a mix of health professionals over one or two consecutive days covering generic and trial specific issues. Recruiter training programmes were well received and some increased recruiters' self-confidence in communicating key RCT concepts to patients. There was, however, little evidence that this training increased actual recruitment rates or patient understanding, satisfaction, or levels of informed consent. There is a need to develop recruiter training programmes that can lead to improved recruitment and informed consent in randomised trials.

Lithium as an adjunct to radioactive iodine for the treatment of hyperthyroidism: a systematic review and meta-analysis.

PubMed

Kessler, Lynn; Palla, Jyothsna; Baru, Joshua S; Onyenwenyi, Chioma; George, Amrutha M; Lucas, Brian P

2014-07-01

Radioactive iodine (RAI) is commonly used in the treatment of hyperthyroidism but is not uniformly successful. Lithium increases thyroidal iodine retention without reducing iodide uptake, increasing the radiation dose to the thyroid when administered with RAI. Although these actions suggest that adjuvant lithium may increase the efficacy of RAI, its role as an adjunct to RAI remains contentious. To evaluate the safety and efficacy of adding lithium to RAI to treat hyperthyroidism. Relevant studies were identified by a search of Medline and the Cochrane Central Register of Controlled Trials. To be included, a study had to be a controlled trial comparing the effect of RAI alone to RAI with lithium in the treatment of hyperthyroidism. Relevant data were extracted and meta-analyses were performed. Of the 75 identified studies, 6 met the inclusion criteria; 4 of these studies were interventional and 2 were observational trials. Meta-analysis of the observational trials (N = 851), both of which were retrospective cohort studies, showed significant improvement in the primary outcome (i.e., cure rate) with adjunctive lithium (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.24 to 2.96). The combined interventional trials (N = 485) also showed an improvement in cure rate, but the difference did not reach statistical significance (OR, 1.28; 95% CI, 0.85 to 1.91). Adjunctive lithium reduced time to cure and blunted thyroid hormone excursions after RAI. Lithium-related side effects were infrequent and usually mild. The observational trials demonstrated significant improvement in the cure rate of hyperthyroidism when lithium is added to RAI. The improvements shown in the interventional trials did not reach statistical significance due to the effect of a single, large negative trial.

A literature review of applied adaptive design methodology within the field of oncology in randomised controlled trials and a proposed extension to the CONSORT guidelines.

PubMed

Mistry, Pankaj; Dunn, Janet A; Marshall, Andrea

2017-07-18

The application of adaptive design methodology within a clinical trial setting is becoming increasingly popular. However the application of these methods within trials is not being reported as adaptive designs hence making it more difficult to capture the emerging use of these designs. Within this review, we aim to understand how adaptive design methodology is being reported, whether these methods are explicitly stated as an 'adaptive design' or if it has to be inferred and to identify whether these methods are applied prospectively or concurrently. Three databases; Embase, Ovid and PubMed were chosen to conduct the literature search. The inclusion criteria for the review were phase II, phase III and phase II/III randomised controlled trials within the field of Oncology that published trial results in 2015. A variety of search terms related to adaptive designs were used. A total of 734 results were identified, after screening 54 were eligible. Adaptive designs were more commonly applied in phase III confirmatory trials. The majority of the papers performed an interim analysis, which included some sort of stopping criteria. Additionally only two papers explicitly stated the term 'adaptive design' and therefore for most of the papers, it had to be inferred that adaptive methods was applied. Sixty-five applications of adaptive design methods were applied, from which the most common method was an adaptation using group sequential methods. This review indicated that the reporting of adaptive design methodology within clinical trials needs improving. The proposed extension to the current CONSORT 2010 guidelines could help capture adaptive design methods. Furthermore provide an essential aid to those involved with clinical trials.

Advice for acute low back pain: a comparison of what research supports and what guidelines recommend.

PubMed

Stevens, Matthew L; Lin, Chung-Wei C; de Carvalho, Flavia A; Phan, Kevin; Koes, Bart; Maher, Chris G

2017-10-01

Advice is widely considered an effective treatment for acute low back pain (LBP); however, details on what and how to deliver this intervention is less clear. We assessed and compared clinical trials that test advice for acute LBP with practice guidelines for their completeness of reporting and concordance on the content, method of delivery, and treatment regimen of advice interventions. Systematic review. Advice randomized controlled trials were identified through a systematic search. Guidelines were taken from recent overviews of guidelines for LBP. Completeness of reporting was assessed using the Template for Intervention Description and Replication checklist. Thematic analysis was used to characterize advice interventions into topics across the aspects of content, method of delivery, and regimen. Concordance between clinical trials and guidelines was assessed by comparing the number of trials that found a statistically significant treatment effect for an intervention that included a specific advice topic with the number of guidelines recommending that topic. The median (interquartile range) completeness of reporting for clinical trials and guidelines was 8 (7-9) and 3 (2-4) out of nine items on the Template for Intervention Description and Replication checklist, respectively. Guideline recommendations were discordant with clinical trials for 50% of the advice topics identified. Completeness of reporting was less than ideal for randomized controlled trials and extremely poor for guidelines. The recommendations made in guidelines of advice for acute LBP were often not concordant with the results of clinical trials. Taken together, these findings mean that the potential clinical value of advice interventions for patients with acute LBP is probably not being realized. Copyright © 2017 Elsevier Inc. All rights reserved.

Carotid artery stenting vs. carotid endarterectomy in the management of carotid artery stenosis: Lessons learned from randomized controlled trials

PubMed Central

Salem, Mohamed M.; Alturki, Abdulrahman Y.; Fusco, Matthew R.; Thomas, Ajith J.; Carter, Bob S.; Chen, Clark C.; Kasper, Ekkehard M.

2018-01-01

Background: Carotid artery stenosis, both symptomatic and asymptomatic, has been well studied with several multicenter randomized trials. The superiority of carotid endarterectomy (CEA) to medical therapy alone in both symptomatic and asymptomatic carotid artery stenosis has been well established in previous trials in the 1990s. The consequent era of endovascular carotid artery stenting (CAS) has offered another option for treating carotid artery stenosis. A series of randomized trials have now been conducted to compare CEA and CAS in the treatment of carotid artery disease. The large number of similar trials has created some confusion due to inconsistent results. Here, the authors review the trials that compare CEA and CAS in the management of carotid artery stenosis. Methods: The PubMed database was searched systematically for randomized controlled trials published in English that compared CEA and CAS. Only human studies on adult patients were assessed. The references of identified articles were reviewed for additional manuscripts to be included if inclusion criteria were met. The following terms were used during search: carotid stenosis, endarterectomy, stenting. Retrospective or single-center studies were excluded from the review. Results: Thirteen reports of seven large-scale prospective multicenter studies, comparing both interventions for symptomatic or asymptomatic extracranial carotid artery stenosis, were identified. Conclusions: While the superiority of intervention to medical management for symptomatic patients has been well established in the literatures, careful selection of asymptomatic patients for intervention should be undertaken and only be pursued after institution of appropriate medical therapy until further reports on trials comparing medical therapy to intervention in this patient group are available. PMID:29740506

Rationale and design of A Trial of Sertraline vs. Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression (ASCEND).

PubMed

Hedayati, S Susan; Daniel, Divya M; Cohen, Scott; Comstock, Bryan; Cukor, Daniel; Diaz-Linhart, Yaminette; Dember, Laura M; Dubovsky, Amelia; Greene, Tom; Grote, Nancy; Heagerty, Patrick; Katon, Wayne; Kimmel, Paul L; Kutner, Nancy; Linke, Lori; Quinn, Davin; Rue, Tessa; Trivedi, Madhukar H; Unruh, Mark; Weisbord, Steven; Young, Bessie A; Mehrotra, Rajnish

2016-03-01

Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes. Published by Elsevier Inc.

Rationale and Design of A Trial of Sertraline vs. Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression (ASCEND)

PubMed Central

Hedayati, S. Susan; Daniel, Divya M.; Cohen, Scott; Comstock, Bryan; Cukor, Daniel; Diaz-Linhart, Yaminette; Dember, Laura M.; Dubovsky, Amelia; Greene, Tom; Grote, Nancy; Heagerty, Patrick; Katon, Wayne; Kimmel, Paul L.; Kutner, Nancy; Linke, Lori; Quinn, Davin; Rue, Tessa; Trivedi, Madhukar H.; Unruh, Mark; Weisbord, Steven; Young, Bessie A.; Mehrotra, Rajnish

2015-01-01

Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes. PMID:26621218

Prevention of EP Migratory Contamination in a Cluster Randomized Trial to Increase tPA Use in Stroke (The INSTINCT Trial)

PubMed Central

Weston, Victoria C.; Meurer, William J.; Frederiksen, Shirley M.; Fox, Allison K.; Scott, Phillip A.

2016-01-01

Objectives Cluster randomized trials (CRTs) are increasingly utilized to evaluate quality improvement interventions aimed at healthcare providers. In trials testing emergency department interventions, migration of emergency physicians (EPs) between hospitals is an important concern, as contamination may affect both internal and external validity. We hypothesized that geographically isolating emergency departments would prevent migratory contamination in a CRT designed to increase ED delivery of tPA in stroke (The INSTINCT Trial). Methods INSTINCT was a prospective, cluster randomized, controlled trial. 24 Michigan community hospitals were randomly selected in matched pairs for study. Contamination was defined at the cluster level, with substantial contamination defined a priori as >10% of EPs affected. Non-adherence, total crossover (contamination + non-adherence), migration distance and characteristics were determined. Results 307 emergency physicians were identified at all sites. Overall, 7 (2.3%) changed study sites. 1 moved between control sites, leaving 6 (2.0%) total crossovers. Of these, 2 (0.7%) moved from intervention to control (contamination) and 4 (1.3%) moved from control to intervention (non-adherence). Contamination was observed in 2 of 12 control sites, with 17% and 9% contamination of the total site EP workforce at follow-up, respectively. Average migration distance was 42 miles for all EPs moving in the study and 35 miles for EPs moving from intervention to control sites. Conclusion The mobile nature of emergency physicians should be considered in the design of quality improvement CRTs. Increased reporting of contamination in CRTs is encouraged to clarify thresholds and facilitate CRT design. PMID:25440230

Behavioral Activation Is an Evidence-Based Treatment for Depression

ERIC Educational Resources Information Center

Sturmey, Peter

2009-01-01

Recent reviews of evidence-based treatment for depression did not identify behavioral activation as an evidence-based practice. Therefore, this article conducted a systematic review of behavioral activation treatment of depression, which identified three meta-analyses, one recent randomized controlled trial and one recent follow-up of an earlier…

Dornase alfa for cystic fibrosis.

PubMed

Yang, Connie; Chilvers, Mark; Montgomery, Mark; Nolan, Sarah J

2016-04-04

Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review. To determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other medications that improve airway clearance, and to identify any adverse events associated with its use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Group's Cystic Fibrosis Register: 30 November 2015.Clinicaltrials.gov was also searched to identify unpublished or ongoing trials. Date of most recent search: 28 November 2015. All randomised and quasi-randomised controlled trials comparing dornase alfa to placebo, standard therapy or other medications that improve airway clearance. Authors independently assessed trials against the inclusion criteria; two authors carried out analysis of methodological quality and data extraction. The searches identified 54 trials, of which 19 (including a total of 2565 participants) met our inclusion criteria. Three additional papers examined the healthcare cost from one of the clinical trials. Fifteen trials compared dornase alfa to placebo or no dornase alfa treatment (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa with hypertonic saline and alternate day dornase alfa (48 participants); one compared dornase alfa to mannitol and the combination of both drugs (38 participants). Trial duration varied from six days to three years.Compared to placebo, forced expiratory volume at one second improved in the intervention groups, with significant differences at one, three, six months and two years. There was also a significant improvement in lung clearance index at one month. There was a decrease in pulmonary exacerbations compared to placebo in trials of longer duration. The quality of the evidence from placebo-controlled trials was moderate to high for outcomes of lung function and pulmonary exacerbations. Limited, low quality evidence was available for changes in quality of life from baseline. One trial that examined the cost of care, including the cost of dornase alfa, found that the cost savings from dornase alfa offset 18% to 38% of the medication costs.The results for trials comparing dornase alfa to other medications that improve airway clearance (hypertonic saline or mannitol) were mixed, with one trial showing a greater improvement in forced expiratory volume at one second for dornase alfa compared to hypertonic saline, and three trials finding no difference between medications. In the only trial to assess the combination of dornase alfa with another medication compared to dornase alone, there was no benefit seen with the combination of dornase alfa and mannitol. Evidence of dornase alfa compared to other medications was limited and the open-label design of the trials may have induced bias, therefore the quality of the evidence was judged to be low.Dornase alfa did not cause significantly more adverse effects, except voice alteration and rash. There is evidence to show that, compared with placebo, therapy with dornase alfa improves lung function in people with cystic fibrosis in trials lasting one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials. There is not enough evidence to firmly conclude if dornase alfa is superior to hyperosmolar agents in improving lung function.

Bioengineered Temporomandibular Joint Disk Implants: Study Protocol for a Two-Phase Exploratory Randomized Preclinical Pilot Trial in 18 Black Merino Sheep (TEMPOJIMS)

PubMed Central

Monje, Florencio Gil; González-García, Raúl; Little, Christopher B; Mónico, Lisete; Pinho, Mário; Santos, Fábio Abade; Carrapiço, Belmira; Gonçalves, Sandra Cavaco; Morouço, Pedro; Alves, Nuno; Moura, Carla; Wang, Yadong; Jeffries, Eric; Gao, Jin; Sousa, Rita; Neto, Lia Lucas; Caldeira, Daniel; Salvado, Francisco

2017-01-01

Background Preclinical trials are essential to test efficacious options to substitute the temporomandibular joint (TMJ) disk. The contemporary absence of an ideal treatment for patients with severe TMJ disorders can be related to difficulties concerning the appropriate study design to conduct preclinical trials in the TMJ field. These difficulties can be associated with the use of heterogeneous animal models, the use of the contralateral TMJ as control, the absence of rigorous randomized controlled preclinical trials with blinded outcomes assessors, and difficulties involving multidisciplinary teams. Objective This study aims to develop a new, reproducible, and effective study design for preclinical research in the TMJ domain, obtaining rigorous data related to (1) identify the impact of bilateral discectomy in black Merino sheep, (2) identify the impact of bilateral discopexy in black Merino sheep, and (3) identify the impact of three different bioengineering TMJ discs in black Merino sheep. Methods A two-phase exploratory randomized controlled preclinical trial with blinded outcomes is proposed. In the first phase, nine sheep are randomized into three different surgical bilateral procedures: bilateral discectomy, bilateral discopexy, and sham surgery. In the second phase, nine sheep are randomized to bilaterally test three different TMJ bioengineering disk implants. The primary outcome is the histological gradation of TMJ. Secondary outcomes are imaging changes, absolute masticatory time, ruminant time per cycle, ruminant kinetics, ruminant area, and sheep weight. Results Previous preclinical studies in this field have used the contralateral unoperated side as a control, different animal models ranging from mice to a canine model, with nonrandomized, nonblinded and uncontrolled study designs and limited outcomes measures. The main goal of this exploratory preclinical protocol is to set a new standard for future preclinical trials in oromaxillofacial surgery, particularly in the TMJ field, by proposing a rigorous design in black Merino sheep. The authors also intend to test the feasibility of pilot outcomes. The authors expect to increase the quality of further studies in this field and to progress in future treatment options for patients undergoing surgery for TMJ disk replacement. Conclusions The study has commenced, but it is too early to provide results or conclusions. PMID:28254733

Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS): rationale and design for meta-analyses of individual patient data of randomized controlled trials that evaluate the effect of physical activity and psychosocial interventions on health-related quality of life in cancer survivors

PubMed Central

2013-01-01

Background Effective interventions to improve quality of life of cancer survivors are essential. Numerous randomized controlled trials have evaluated the effects of physical activity or psychosocial interventions on health-related quality of life of cancer survivors, with generally small sample sizes and modest effects. Better targeted interventions may result in larger effects. To realize such targeted interventions, we must determine which interventions that are presently available work for which patients, and what the underlying mechanisms are (that is, the moderators and mediators of physical activity and psychosocial interventions). Individual patient data meta-analysis has been described as the ‘gold standard’ of systematic review methodology. Instead of extracting aggregate data from study reports or from authors, the original research data are sought directly from the investigators. Individual patient data meta-analyses allow for adequate statistical analysis of intervention effects and moderators of such effects. Here, we report the rationale and design of the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) Consortium. The primary aim of POLARIS is 1) to conduct meta-analyses based on individual patient data to evaluate the effect of physical activity and psychosocial interventions on the health-related quality of life of cancer survivors; 2) to identify important demographic, clinical, personal, or intervention-related moderators of the effect; and 3) to build and validate clinical prediction models identifying the most relevant predictors of intervention success. Methods/Design We will invite investigators of randomized controlled trials that evaluate the effects of physical activity and/or psychosocial interventions on health-related quality of life compared with a wait-list, usual care or attention control group among adult cancer survivors to join the POLARIS consortium and share their data for use in pooled analyses that will address the proposed aims. We are in the process of identifying eligible randomized controlled trials through literature searches in four databases. To date, we have identified 132 eligible and unique trials. Discussion The POLARIS consortium will conduct the first individual patient data meta-analyses in order to generate evidence essential to targeting physical activity and psychosocial programs to the individual survivor’s characteristics, capabilities, and preferences. Registration PROSPERO: International prospective register of systematic reviews, CRD42013003805 PMID:24034173

High-Dose Conformal Radiotherapy Reduces Prostate Cancer-Specific Mortality: Results of a Meta-analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Viani, Gustavo Arruda, E-mail: gusviani@gmail.com; Godoi Bernardes da Silva, Lucas; Stefano, Eduardo Jose

2012-08-01

Purpose: To determine in a meta-analysis whether prostate cancer-specific mortality (PCSM), biochemical or clinical failure (BCF), and overall mortality (OM) in men with localized prostate cancer treated with conformal high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT). Methods and Materials: The MEDLINE, Embase, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing conformal HDRT with CDRT for localized prostate cancer. Results: Five randomized, controlled trials (2508 patients) that met the study criteria were identified. Pooled results from these randomized, controlled trialsmore » showed a significant reduction in the incidence of PCSM and BCF rates at 5 years in patients treated with HDRT (p = 0.04 and p < 0.0001, respectively), with an absolute risk reduction (ARR) of PCSM and BCF at 5 years of 1.7% and 12.6%, respectively. Two trials evaluated PCSM with 10 years of follow up. The pooled results from these trials showed a statistical benefit for HDRT in terms of PCSM (p = 0.03). In the subgroup analysis, trials that used androgen deprivation therapy (ADT) showed an ARR for BCF of 12.9% (number needed to treat = 7.7, p < 0.00001), whereas trials without ADT had an ARR of 13.6% (number needed to treat = 7, p < 0.00001). There was no difference in the OM rate at 5 and 10 years (p = 0.99 and p = 0.11, respectively) between the groups receiving HDRT and CDRT. Conclusions: This meta-analysis is the first study to show that HDRT is superior to CDRT in preventing disease progression and prostate cancer-specific death in trials that used conformational technique to increase the total dose. Despite the limitations of our study in evaluating the role of ADT and HDRT, our data show no benefit for HDRT arms in terms of BCF in trials with or without ADT.« less

How standard is standard care? Exploring control group outcomes in behaviour change interventions for young people with type 1 diabetes.

PubMed

Ayling, K; Brierley, S; Johnson, B; Heller, S; Eiser, C

2015-01-01

Poor descriptions of standard care may compromise interpretation of results in randomised controlled trials (RCTs) of health interventions. We investigated quality of standard care in RCTs of behaviour change interventions for young people with type 1 diabetes and consider implications for evaluating trial outcomes. We conducted systematic searches for articles published between 1999 and 2012. We extracted standard care descriptions and contacted trial authors to complete a checklist of standard care activities. The relationship between standard care quality and outcomes was examined via subgroup meta-analyses and meta-regression. Standard care descriptions, standard care quality, and relationships between standard care quality with medical and psychological outcomes. We identified 20 RCTs described across 26 articles. Published descriptions of standard care were limited to service-level features. Author responses indicated standard care provision extended beyond published accounts. Subgroup analyses suggested control groups receiving higher standard care quality showed larger improvements in both medical and psychological outcomes, although standard care quality did not predict outcomes significantly. The quality of care delivered to control group participants can influence outcomes of RCTs. Inadequate reporting exacerbates this issue by masking variations between trials. We argue for increased clarity in reporting standard care in future trials.

Mechanisms of change in control group drinking in clinical trials of brief alcohol intervention: implications for bias toward the null.

PubMed

Bernstein, Judith A; Bernstein, Edward; Heeren, Timothy C

2010-09-01

Reductions in control group consumption over time that are possibly related to research design affect the impact of brief alcohol interventions (BAI) in clinical settings. We conducted a systematic review to identify research design factors that may contribute to control group change, strategies to limit these effects and implications for researchers. Studies with control group n > 30 were selected if they published baseline and outcome consumption data, conducted trials in clinical settings in Anglophone countries and did not censor gender or age. Among 38 studies cited in 20 reviews through October 2009, 16 met criteria (n = 31-370). In 54%, controls received alcohol specific handouts, advice and/or referral. Both the number and depth of assessments were highly variable. The percentage change in consumption ranged from-0.10 to-0.84 (mean-0.32), and effect size from 0.04 to 0.70 (mean 0.37). Published data were insufficient for meta-analysis. Researchers should consider strategies to reduce the impact of research design factors, such as procedures to enhance sample diversity, blind subjects to study purpose to limit social desirability bias, reduce the number and depth of instruments (assessment reactivity), and finally, analytic techniques to decrease the impact of outliers and regression to the mean. This review identifies problems with retrospective analysis of predictors of control group change, and underscores the need to design prospective studies to permit identification, quantification and adjustment for potential sources of bias in BAI trials.

The REFLECT statement: methods and processes of creating reporting guidelines for randomized controlled trials for livestock and food safety.

PubMed

O'Connor, A M; Sargeant, J M; Gardner, I A; Dickson, J S; Torrence, M E; Dewey, C E; Dohoo, I R; Evans, R B; Gray, J T; Greiner, M; Keefe, G; Lefebvre, S L; Morley, P S; Ramirez, A; Sischo, W; Smith, D R; Snedeker, K; Sofos, J; Ward, M P; Wills, R

2010-01-01

The conduct of randomized controlled trials in livestock with production, health, and food-safety outcomes presents unique challenges that may not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A two-day consensus meeting was held on November 18-19, 2008 in Chicago, IL, United States of America, to achieve the objective. Prior to the meeting, a Web-based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food-safety researchers, livestock-production specialists, journal editors, assistant editors, and associate editors. Prior to the meeting, the attendees completed a Web-based survey indicating which CONSORT statement items may need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines For Randomized Control Trials) statement for livestock and food safety (LFS) and 22-item checklist. Fourteen items were modified from the CONSORT checklist, and an additional sub-item was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health, and food-safety outcomes.

The REFLECT statement: methods and processes of creating reporting guidelines for randomized controlled trials for livestock and food safety by modifying the CONSORT statement.

PubMed

O'Connor, A M; Sargeant, J M; Gardner, I A; Dickson, J S; Torrence, M E; Dewey, C E; Dohoo, I R; Evans, R B; Gray, J T; Greiner, M; Keefe, G; Lefebvre, S L; Morley, P S; Ramirez, A; Sischo, W; Smith, D R; Snedeker, K; Sofos, J; Ward, M P; Wills, R

2010-03-01

The conduct of randomized controlled trials in livestock with production, health and food-safety outcomes presents unique challenges that may not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A 2-day consensus meeting was held on 18-19 November 2008 in Chicago, IL, USA, to achieve the objective. Prior to the meeting, a Web-based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food-safety researchers, livestock-production specialists, journal editors, assistant editors and associate editors. Prior to the meeting, the attendees completed a Web-based survey indicating which CONSORT statement items may need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines for Randomized Control Trials) statement for livestock and food safety and 22-item checklist. Fourteen items were modified from the CONSORT checklist and an additional sub-item was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health and food-safety outcomes.

The REFLECT statement: methods and processes of creating reporting guidelines for randomized controlled trials for livestock and food safety.

PubMed

O'Connor, A M; Sargeant, J M; Gardner, I A; Dickson, J S; Torrence, M E; Dewey, C E; Dohoo, I R; Evans, R B; Gray, J T; Greiner, M; Keefe, G; Lefebvre, S L; Morley, P S; Ramirez, A; Sischo, W; Smith, D R; Snedeker, K; Sofos, J N; Ward, M P; Wills, R

2010-01-01

The conduct of randomized controlled trials in livestock with production, health, and food-safety outcomes presents unique challenges that may not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A two-day consensus meeting was held on November 18-19, 2008 in Chicago, Ill, United States of America, to achieve the objective. Prior to the meeting, a Web-based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food-safety researchers, livestock production specialists, journal editors, assistant editors, and associate editors. Prior to the meeting, the attendees completed a Web-based survey indicating which CONSORT statement items may need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines for Randomized Control Trials) statement for livestock and food safety (LFS) and 22-item checklist. Fourteen items were modified from the CONSORT checklist, and an additional sub-item was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health, and food-safety outcomes.

Independent exercise for glottal incompetence to improve vocal problems and prevent aspiration pneumonia in the elderly: a randomized controlled trial.

PubMed

Fujimaki, Yoko; Tsunoda, Koichi; Kobayashi, Rika; Tonghyo, Chong; Tanaka, Fujinobu; Kuroda, Hiroyuki; Numata, Tsutomu; Ishii, Toyota; Kuroda, Reiko; Masuda, Sawako; Hashimoto, Sho; Misawa, Hayato; Shindo, Naoko; Mori, Takahiro; Mori, Hiroko; Uchiyama, Naoki; Kamei, Yuichirou; Tanaka, Masashi; Hamaya, Hironobu; Funatsuki, Shingo; Usui, Satoko; Ito, Ikuno; Hamada, Kohei; Shindo, Akihito; Tokumaru, Yutaka; Morita, Yoko; Ueha, Rumi; Nito, Takaharu; Kikuta, Shu; Sekimoto, Sotaro; Kondo, Kenji; Sakamoto, Takashi; Itoh, Kenji; Yamasoba, Tatsuya; Matsumoto, Sumio

2017-08-01

To evaluate the effect of a self-controlled vocal exercise in elderly people with glottal closure insufficiency. Parallel-arm, individual randomized controlled trial. Patients who visited one of 10 medical centers under the National Hospital Organization group in Japan for the first time, aged 60 years or older, complaining of aspiration or hoarseness, and endoscopically confirmed to have glottal closure insufficiency owing to vocal cord atrophy, were enrolled in this study. They were randomly assigned to an intervention or a control group. The patients of the intervention group were given guidance and a DVD about a self-controlled vocal exercise. The maximum phonation time which is a measure of glottal closure was evaluated, and the number of patients who developed pneumonia during the six months was compared between the two groups. Of the 543 patients enrolled in this trial, 259 were allocated into the intervention group and 284 into the control; 60 of the intervention group and 75 of the control were not able to continue the trial. A total of 199 patients (age 73.9 ±7.25 years) in the intervention group and 209 (73.3 ±6.68 years) in the control completed the six-month trial. Intervention of the self-controlled vocal exercise extended the maximum phonation time significantly ( p < 0.001). There were two hospitalizations for pneumonia in the intervention group and 18 in the control group, representing a significant difference ( p < 0.001). The self-controlled vocal exercise allowed patients to achieve vocal cord adduction and improve glottal closure insufficiency, which reduced the rate of hospitalization for pneumonia significantly. gov Identifier-UMIN000015567.

Pharmacological Treatment of Cannabis-Related Disorders: A Narrative Review.

PubMed

Gorelick, David A

2016-01-01

Cannabis is the most widely used illicit psychoactive substance world-wide, yet no medication is approved for the treatment of intoxication, withdrawal, or cannabis use disorder (CUD). To comprehensively review the current state of knowledge. Search of the PubMed electronic data base and review of reference lists of relevant articles to identify controlled clinical trials of pharmacological treatment. The search identified 4 trials for specific intoxication symptoms (none for global intoxication), 7 trials for withdrawal, and 12 phase II trials for CUD. One or two trials each suggest that propranolol is effective for some intoxication symptoms, antipsychotics for cannabis-induced psychosis, and dronabinol (synthetic THC) and gabapentin for cannabis withdrawal. Of 10 medications and one medication combination studied in 12 trials for CUD, only two medications were effective (in single trials): gabapentin and Nacetylcysteine (in adolescents). Not effective were dronabinol and several antidepressants, anticonvulsants, and antianxiety medications. Three trials of antidepressants for CUD with comorbid depression gave inconsistent results. A trial of atomoxetine for CUD with comorbid ADHD showed no efficacy. Five trials of second-generation antipsychotics for CUD with comorbid schizophrenia showed none better than any other. Further research is needed to confirm the efficacy of gabapentin for withdrawal and gabapentin and N-acetylcysteine for CUD and to develop new medications for all 3 cannabis-related disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Waste the waist: a pilot randomised controlled trial of a primary care based intervention to support lifestyle change in people with high cardiovascular risk.

PubMed

Greaves, Colin; Gillison, Fiona; Stathi, Afroditi; Bennett, Paul; Reddy, Prasuna; Dunbar, James; Perry, Rachel; Messom, Daniel; Chandler, Roger; Francis, Margaret; Davis, Mark; Green, Colin; Evans, Philip; Taylor, Gordon

2015-01-16

In the UK, thousands of people with high cardiovascular risk are being identified by a national risk-assessment programme (NHS Health Checks). Waste the Waist is an evidence-informed, theory-driven (modified Health Action Process Approach), group-based intervention designed to promote healthy eating and physical activity for people with high cardiovascular risk. This pilot randomised controlled trial aimed to assess the feasibility of delivering the Waste the Waist intervention in UK primary care and of conducting a full-scale randomised controlled trial. We also conducted exploratory analyses of changes in weight. Patients aged 40-74 with a Body Mass Index of 28 or more and high cardiovascular risk were identified from risk-assessment data or from practice database searches. Participants were randomised, using an online computerised randomisation algorithm, to receive usual care and standardised information on cardiovascular risk and lifestyle (Controls) or nine sessions of the Waste the Waist programme (Intervention). Group allocation was concealed until the point of randomisation. Thereafter, the statistician, but not participants or data collectors were blinded to group allocation. Weight, physical activity (accelerometry) and cardiovascular risk markers (blood tests) were measured at 0, 4 and 12 months. 108 participants (22% of those approached) were recruited (55 intervention, 53 controls) from 6 practices and 89% provided data at both 4 and 12 months. Participants had a mean age of 65 and 70% were male. Intervention participants attended 72% of group sessions. Based on last observations carried forward, the intervention group did not lose significantly more weight than controls at 12 months, although the difference was significant when co-interventions and co-morbidities that could affect weight were taken into account (Mean Diff 2.6Kg. 95%CI: -4.8 to -0.3, p = 0.025). No significant differences were found in physical activity. The Waste the Waist intervention is deliverable in UK primary care, has acceptable recruitment and retention rates and produces promising preliminary weight loss results. Subject to refinement of the physical activity component, it is now ready for evaluation in a full-scale trial. Current Controlled Trials ISRCTN10707899 .

Moving Beyond Conventional Clinical Trial End Points in Treatment-refractory Metastatic Colorectal Cancer: A Composite Quality-of-life and Symptom Control End Point.

PubMed

Gong, Jun; Wu, Daniel; Chuang, Jeremy; Tuli, Richard; Simard, John; Hendifar, Andrew

2017-11-01

This review highlights the evidence supporting symptom control and quality-of-life (QOL) measures as predictors of survival in treatment-refractory metastatic colorectal cancer (mCRC) and describes a composite symptom control and QOL end point recently reported in a Phase III trial that may serve as a more reasonable end point of efficacy in this population. A literature search was conducted using MEDLINE to identify clinical studies (including case series and observational, retrospective, and prospective studies) that reported the predictive value of QOL measures for survival in mCRC. The search was limited by the following key words: quality of life, survival, and colorectal cancer. We then performed a second search limited to studies of randomized and Phase III design in mCRC to identify studies that used QOL assessments as their primary end points. A manual search was also performed to include additional studies of potential relevance. There is increasing evidence to support that symptom control and QOL measures are predictors of survival in treatment-refractory mCRC and can serve as an alternative but equally as important end point to survival in this population. A recent large, randomized Phase III trial using a composite primary end point of lean body mass, pain, anorexia, and fatigue reported the feasibility in evaluating benefit in mCRC beyond conventional clinical trial end points. Future studies in treatment-refractory mCRC may be better served by evaluating improvement in symptom control and QOL, which may otherwise serve as the best predictor of survival in last-line treatment settings. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Study protocol: a randomised placebo-controlled clinical trial to study the effect of vitamin D supplementation on glycaemic control in type 2 Diabetes Mellitus SUNNY trial.

PubMed

Krul-Poel, Yvonne H M; van Wijland, Hans; Stam, Frank; ten Boekel, Edwin; Lips, Paul; Simsek, Suat

2014-07-17

Besides the classical role of vitamin D on calcium and bone homeostasis, vitamin D deficiency has recently been identified as a contributing factor in the onset of insulin resistance in type 2 diabetes mellitus. However, it is uncertain whether vitamin D deficiency and poor glycaemic control are causally interrelated or that they constitute two independent features of type 2 diabetes mellitus. There are limited clinical trials carried out which measured the effect of vitamin D supplementation on glycaemic control.The objective of this study is to investigate the effect of vitamin D supplementation on glycaemic control and quality of life in patients with type 2 diabetes mellitus. In a randomised double-blind placebo-controlled trial conducted in five general practices in the Netherlands three hundred patients with type 2 diabetes mellitus treated with lifestyle advises or metformin or sulphonylurea-derivatives are randomised to receive either placebo or 50,000 IU Vitamin D3 at monthly intervals. The primary outcome measure is the change in glycated haemoglobin level between baseline and six months. Secondary outcome measures include blood pressure, anthropometric parameters, lipid profile, insulin resistance, quality of life, advanced glycation end products and safety profiles. Quality of life will be measured by The Short Form (SF-36) Health Survey questionnaire. Advanced glycation end products are measured by an AGE-reader. This trial will be the first study exploring the effect of vitamin D supplementation on both glycaemic control and quality of life in patients with type 2 diabetes mellitus. Our findings will contribute to the knowledge of the relationship between vitamin D status and insulin resistance in patients with type 2 diabetes mellitus. The Netherlands trial register: NTR3154.

CENTRAL, PEDro, PubMed, and EMBASE are the most comprehensive databases indexing randomized controlled trials of physical therapy interventions.

PubMed

Michaleff, Zoe A; Costa, Leonardo O P; Moseley, Anne M; Maher, Christopher G; Elkins, Mark R; Herbert, Robert D; Sherrington, Catherine

2011-02-01

Many bibliographic databases index research studies evaluating the effects of health care interventions. One study has concluded that the Physiotherapy Evidence Database (PEDro) has the most complete indexing of reports of randomized controlled trials of physical therapy interventions, but the design of that study may have exaggerated estimates of the completeness of indexing by PEDro. The purpose of this study was to compare the completeness of indexing of reports of randomized controlled trials of physical therapy interventions by 8 bibliographic databases. This study was an audit of bibliographic databases. Prespecified criteria were used to identify 400 reports of randomized controlled trials from the reference lists of systematic reviews published in 2008 that evaluated physical therapy interventions. Eight databases (AMED, CENTRAL, CINAHL, EMBASE, Hooked on Evidence, PEDro, PsycINFO, and PubMed) were searched for each trial report. The proportion of the 400 trial reports indexed by each database was calculated. The proportions of the 400 trial reports indexed by the databases were as follows: CENTRAL, 95%; PEDro, 92%; PubMed, 89%; EMBASE, 88%; CINAHL, 53%; AMED, 50%; Hooked on Evidence, 45%; and PsycINFO, 6%. Almost all of the trial reports (99%) were found in at least 1 database, and 88% were indexed by 4 or more databases. Four trial reports were uniquely indexed by a single database only (2 in CENTRAL and 1 each in PEDro and PubMed). The results are only applicable to searching for English-language published reports of randomized controlled trials evaluating physical therapy interventions. The 4 most comprehensive databases of trial reports evaluating physical therapy interventions were CENTRAL, PEDro, PubMed, and EMBASE. Clinicians seeking quick answers to clinical questions could search any of these databases knowing that all are reasonably comprehensive. PEDro, unlike the other 3 most complete databases, is specific to physical therapy, so studies not relevant to physical therapy are less likely to be retrieved. Researchers could use CENTRAL, PEDro, PubMed, and EMBASE in combination to conduct exhaustive searches for randomized trials in physical therapy.

A Community Resource Map to Support Clinical-Community Linkages in a Randomized Controlled Trial of Childhood Obesity, Eastern Massachusetts, 2014-2016.

PubMed

Fiechtner, Lauren; Puente, Gabriella C; Sharifi, Mona; Block, Jason P; Price, Sarah; Marshall, Richard; Blossom, Jeff; Gerber, Monica W; Taveras, Elsie M

2017-07-06

Novel approaches to health care delivery that leverage community resources could improve outcomes for children at high risk for obesity. We describe the process by which we created an online interactive community resources map for use in the Connect for Health randomized controlled trial. The trial was conducted in the 6 pediatric practices that cared for the highest percentage of children with overweight or obesity within a large multi-specialty group practice in eastern Massachusetts. By using semistructured interviews with parents and community partners and geographic information systems (GIS), we created and validated a community resource map for use in a randomized controlled trial for childhood obesity. We conducted semistructured interviews with 11 parents and received stakeholder feedback from 5 community partners, 2 pediatricians, and 3 obesity-built environment experts to identify community resources that could support behavior change. We used GIS databases to identify the location of resources. After the resources were validated, we created an online, interactive searchable map. We evaluated parent resource empowerment at baseline and follow-up, examined if the participant families went to new locations for physical activity and food shopping, and evaluated how satisfied the families were with the information they received. Parents, community partners, and experts identified several resources to be included in the map, including farmers markets, supermarkets, parks, and fitness centers. Parents expressed the need for affordable activities. Parent resource empowerment increased by 0.25 units (95% confidence interval, 0.21-0.30) over the 1-year intervention period; 76.2% of participants were physically active at new places, 57.1% of participant families shopped at new locations; and 71.8% reported they were very satisfied with the information they received. Parents and community partners identified several community resources that could help support behavior change. Parent resource empowerment and use of community resources increased over the intervention period, suggesting that community resource mapping should inform future interventions.

Improving self-management of cancer risk factors, underscreening for cancer and depression among general practice patients: study protocol of a randomised controlled trial

PubMed Central

Carey, Mariko; Sanson-Fisher, Rob; Oldmeadow, Christopher; Mansfield, Elise; Walsh, Justin

2016-01-01

Introduction General practitioners have a key role in reducing cancer risk factors, screening for cancer and managing depression. Given the time-limited nature of consultations, a new and more time-efficient approach is needed which addresses multiple health needs simultaneously, and encourages patient self-management to address health risks. The aim of this cluster randomised controlled trial is to test the effectiveness of a patient feedback intervention in improving patient self-management of health needs related to smoking, risky alcohol consumption and underscreening for cancers at 1 month follow-up. Methods and analysis Adult general practice patients will be invited to participate in a baseline survey to assess cancer risk factors, screening needs and depression. A total of 360 participants identified by the baseline survey as having at least one health need (a self-reported cancer risk factor, underscreening for cancer, or an elevated depression score) will be randomised to an intervention or control group. Participants in the intervention group will receive tailored printed feedback summarising their identified health needs and recommended self-management actions to address these. All participants will be invited to complete a telephone interview 1 month following recruitment to assess self-management actions taken in relation to health needs identified in the baseline survey. Control group participants will receive tailored printed feedback on their identified health needs after their follow-up interview. A logistic regression model, with group allocation as the main predictor, will be used to assess the impact of the intervention on self-management actions. Ethical considerations and dissemination Participants identified as being at risk of depression will be advised to speak with their doctor. Results will be disseminated via publication in peer-reviewed journals. The study has been approved by the University of Newcastle Human Research Ethics Committee. Trial registration number ACTRN12616001443482. PMID:27864255

What is different about workers' compensation patients? Socioeconomic predictors of baseline disability status among patients with lumbar radiculopathy.

PubMed

Atlas, Steven J; Tosteson, Tor D; Hanscom, Brett; Blood, Emily A; Pransky, Glenn S; Abdu, William A; Andersson, Gunnar B; Weinstein, James N

2007-08-15

Combined analysis of 2 prospective clinical studies. To identify socioeconomic characteristics associated with workers' compensation in patients with an intervertebral disc herniation (IDH) or spinal stenosis (SpS). Few studies have compared socioeconomic differences between those receiving or not receiving workers' compensation with the same underlying clinical conditions. Patients were identified from the Spine Patient Outcomes Research Trial (SPORT) and the National Spine Network (NSN) practice-based outcomes study. Patients with IDH and SpS within NSN were identified satisfying SPORT eligibility criteria. Information on disability and work status at baseline evaluation was used to categorize patients into 3 groups: workers' compensation, other disability compensation, or work-eligible controls. Enrollment rates of patients with disability in a clinical efficacy trial (SPORT) and practice-based network (NSN) were compared. Independent socioeconomic predictors of baseline workers' compensation status were identified in multivariate logistic regression models controlling for clinical condition, study cohort, and initial treatment designation. Among 3759 eligible patients (1480 in SPORT and 2279 in NSN), 564 (15%) were receiving workers' compensation, 317 (8%) were receiving other disability compensation, and 2878 (77%) were controls. Patients receiving workers' compensation were less common in SPORT than NSN (9.2% vs. 18.8%, P < 0.001), but patients receiving other disability compensation were similarly represented (8.9% vs. 7.7%, P = 0.19). In univariate analyses, many socioeconomic characteristics significantly differed according to baseline workers' compensation status. In multiple logistic regression analyses, gender, educational level, work characteristics, legal action, and expectations about ability to work without surgery were independently associated with receiving workers' compensation. Clinical trials involving conditions commonly seen in patients with workers' compensation may need special efforts to ensure adequate representation. Socioeconomic characteristics markedly differed between patients receiving and not receiving workers' compensation. Identifying the independent effects of workers' compensation on outcomes will require controlling for these baseline characteristics and other clinical features associated with disability status.

What Is Different About Worker’s Compensation Patients?

PubMed Central

Atlas, Steven J.; Tosteson, Tor D.; Hanscom, Brett; Blood, Emily A.; Pransky, Glenn S.; Abdu, William A.; Andersson, Gunnar B.; Weinstein, James N.

2010-01-01

Study Design Combined analysis of 2 prospective clinical studies. Objective To identify socioeconomic characteristics associated with workers’ compensation in patients with an intervertebral disc herniation (IDH) or spinal stenosis (SpS). Summary of Background Data Few studies have compared socioeconomic differences between those receiving or not receiving workers’ compensation with the same underlying clinical conditions. Methods Patients were identified from the Spine Patient Outcomes Research Trial (SPORT) and the National Spine Network (NSN) practice-based outcomes study. Patients with IDH and SpS within NSN were identified satisfying SPORT eligibility criteria. Information on disability and work status at baseline evaluation was used to categorize patients into 3 groups: workers’ compensation, other disability compensation, or work-eligible controls. Enrollment rates of patients with disability in a clinical efficacy trial (SPORT) and practice-based network (NSN) were compared. Independent socioeconomic predictors of baseline workers’ compensation status were identified in multivariate logistic regression models controlling for clinical condition, study cohort, and initial treatment designation. Results Among 3759 eligible patients (1480 in SPORT and 2279 in NSN), 564 (15%) were receiving workers’ compensation, 317 (8%) were receiving other disability compensation, and 2878 (77%) were controls. Patients receiving workers’ compensation were less common in SPORT than NSN (9.2% vs. 18.8%, P < 0.001), but patients receiving other disability compensation were similarly represented (8.9% vs. 7.7%, P = 0.19). In univariate analyses, many socioeconomic characteristics significantly differed according to baseline workers’ compensation status. In multiple logistic regression analyses, gender, educational level, work characteristics, legal action, and expectations about ability to work without surgery were independently associated with receiving workers’ compensation. Conclusion Clinical trials involving conditions commonly seen in patients with workers’ compensation may need special efforts to ensure adequate representation. Socioeconomic characteristics markedly differed between patients receiving and not receiving workers’ compensation. Identifying the independent effects of workers’ compensation on outcomes will require controlling for these baseline characteristics and other clinical features associated with disability status. PMID:17700451

Is conflict adaptation due to active regulation or passive carry-over? Evidence from eye movements.

PubMed

Hubbard, Jason; Kuhns, David; Schäfer, Theo A J; Mayr, Ulrich

2017-03-01

Conflict-adaptation effects (i.e., reduced response-time costs on high-conflict trials following high-conflict trials) supposedly represent our cognitive system's ability to regulate itself according to current processing demands. However, currently it is not clear whether these effects reflect conflict-triggered, active regulation, or passive carry-over of previous-trial control settings. We used eye movements to examine whether the degree of experienced conflict modulates conflict-adaptation effects, as the conflict-triggered regulation view predicts. Across 2 experiments in which participants had to identify a target stimulus based on an endogenous cue while-on conflict trials-having to resist a sudden-onset distractor, we found a clear indication of conflict adaptation. This adaptation effect disappeared however, when participants inadvertently fixated the sudden-onset distractor on the previous trial-that is, when they experienced a high degree of conflict. This pattern of results suggests that conflict adaptation can be explained parsimoniously in terms of a broader memory process that retains recently adopted control settings across trials. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Effectiveness and cost-effectiveness of humanistic counselling in schools for young people with emotional distress (ETHOS): study protocol for a randomised controlled trial.

PubMed

Stafford, Megan Rose; Cooper, Mick; Barkham, Michael; Beecham, Jeni; Bower, Peter; Cromarty, Karen; Fugard, Andrew J B; Jackson, Charlie; Pearce, Peter; Ryder, Rebekah; Street, Cathy

2018-03-09

One in ten children in Britain have been identified as experiencing a diagnosable mental health disorder. School-based humanistic counselling (SBHC) may help young people identify, address, and overcome psychological distress. Data from four pilot trials suggest that SBHC may be clinically effective. However, a fully powered randomised controlled trial (RCT) is needed to provide a robust test of its effectiveness, to assess its cost-effectiveness, and to determine the process of change. The Effectiveness and Cost-effectiveness Trial of Humanistic Counselling in Schools (ETHOS) is a two-arm, parallel-group RCT comparing the clinical and cost-effectiveness of SBHC with Pastoral Care as Usual (PCAU) in school settings. Eligibility criteria for young people include being between 13 and 16 years of age and experiencing moderate to severe levels of emotional distress. Participants are randomised to receive either SBHC or PCAU. SBHC is delivered in up to 10 weekly, individual sessions in their school with a qualified, experienced counsellor who has also received training using a clinical practice manual. Adherence to the SBHC model is assessed by a sub-team of auditors and in clinical supervision. PCAU consists of the schools' pre-existing systems for supporting the emotional health and well-being of students. The primary outcomes are psychological distress measured using the Young Person's Clinical Outcomes in Routine Evaluation (YP-CORE) and costs evaluated using the Client Service Receipt Inventory (CSRI). Secondary outcomes include psychological difficulties, levels of depression, anxiety and self-esteem, well-being, school engagement, educational outcomes and achievement of personal goals. Qualitative interviews with participants, parents and school staff will look to identify the mechanisms of change in SBHC. Researchers administering the measures are blind to allocation. The trial requires n = 306 participants (n = 153 in each group), with 90% power to detect a standardised mean difference (SMD) of 0.5. An intention-to-treat analysis will be undertaken. This RCT is powered to detect clinically meaningful differences, and will make a major contribution to the evidence base for mental health provision for adolescents. It will have implications for all stakeholders, including policy-makers, statutory advisory bodies for child welfare, head teachers, children and young people practitioners, child welfare and parenting organisations, and young people. Controlled Trials International Standard Randomised Controlled Trial Number (ISRCTN) Registry, ID: ISRCTN10460622 . Registered on 11 May 2016.

Efficacy of Intensive Control of Glucose in Stroke Prevention: A Meta-Analysis of Data from 59197 Participants in 9 Randomized Controlled Trials

PubMed Central

Zhang, Chi; Zhou, Yu-Hao; Xu, Chun-Li; Chi, Feng-Ling; Ju, Hai-Ning

2013-01-01

Background The efficacy of treatments that lower glucose in reducing the risk of incident stroke remains unclear. We therefore did a systematic review and meta-analysis to evaluate the efficacy of intensive control of glucose in the prevention of stroke. Methodology/Principal Findings We systematically searched Medline, EmBase, and the Cochrane Library for trials published between 1950 and June, 2012. We included randomized controlled trials that reported on the effects of intensive control of glucose on incident stroke compared with standard care. Summary estimates of relative risk (RR) reductions were calculated with a random effects model, and the analysis was further stratified by factors that could affect the treatment effects. Of 649 identified studies, we included nine relevant trials, which provided data for 59197 patients and 2037 events of stroke. Overall, intensive control of glucose as compared to standard care had no effect on incident stroke (RR, 0.96; 95%CI 0.88–1.06; P = 0.445). In the stratified analyses, a beneficial effect was seen in those trials when body mass index (BMI) more than 30 (RR, 0.86; 95%CI: 0.75–0.99; P = 0.041). No other significant differences were detected between the effect of intensive control of glucose and standard care when based on other subset factors. Conclusions/Significance Our study indicated intensive control of glucose can effectively reduce the risk of incident stroke when patients with BMI more than 30. PMID:23372729

Robotic-assisted versus laparoscopic colorectal surgery: a meta-analysis of four randomized controlled trials

PubMed Central

2014-01-01

Background Robotic-assisted laparoscopy is popularly performed for colorectal disease. The objective of this meta-analysis was to compare the safety and efficacy of robotic-assisted colorectal surgery (RCS) and laparoscopic colorectal surgery (LCS) for colorectal disease based on randomized controlled trial studies. Methods Literature searches of electronic databases (Pubmed, Web of Science, and Cochrane Library) were performed to identify randomized controlled trial studies that compared the clinical or oncologic outcomes of RCS and LCS. This meta-analysis was performed using the Review Manager (RevMan) software (version 5.2) that is provided by the Cochrane Collaboration. The data used were mean differences and odds ratios for continuous and dichotomous variables, respectively. Fixed-effects or random-effects models were adopted according to heterogeneity. Results Four randomized controlled trial studies were identified for this meta-analysis. In total, 110 patients underwent RCS, and 116 patients underwent LCS. The results revealed that estimated blood losses (EBLs), conversion rates and times to the recovery of bowel function were significantly reduced following RCS compared with LCS. There were no significant differences in complication rates, lengths of hospital stays, proximal margins, distal margins or harvested lymph nodes between the two techniques. Conclusions RCS is a promising technique and is a safe and effective alternative to LCS for colorectal surgery. The advantages of RCS include reduced EBLs, lower conversion rates and shorter times to the recovery of bowel function. Further studies are required to define the financial effects of RCS and the effects of RCS on long-term oncologic outcomes. PMID:24767102

The early use of botulinum toxin in post-stroke spasticity: study protocol for a randomised controlled trial.

PubMed

Lindsay, Cameron; Simpson, Julie; Ispoglou, Sissi; Sturman, Steve G; Pandyan, Anand D

2014-01-08

Patients surviving stroke but who have significant impairment of function in the affected arm are at more risk of developing pain, stiffness and contractures. The abnormal muscle activity, associated with post-stroke spasticity, is thought to be causally associated with the development of these complications. Treatment of spasticity is currently delayed until a patient develops signs of these complications. This protocol is for a phase II study that aims to identify whether using OnabotulinumtoxinA (BoNT-A) in combination with physiotherapy early post stroke when initial abnormal muscle activity is neurophysiologically identified can prevent loss of range at joints and improve functional outcomes.The trial uses a screening phase to identify which people are appropriate to be included in a double blind randomised placebo-controlled trial. All patients admitted to Sandwell and West Birmingham NHS Trust Hospitals with a diagnosis of stroke will be screened to identify functional activity in the arm. Those who have no function will be appropriate for further screening. Patients who are screened and have abnormal muscle activity identified on EMG will be given electrical stimulation to forearm extensors for 3 months and randomised to have either injections of BoNT-A or normal saline. The primary outcome measure is the action research arm test - a measure of arm function. Further measures include spasticity, stiffness, muscle strength and fatigue as well as measures of quality of life, participation and caregiver strain. ISRCTN57435427, EudraCT2010-021257-39, NCT01882556.

What's in a title? An assessment of whether randomized controlled trial in a title means that it is one.

PubMed

Koletsi, Despina; Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

2012-06-01

In this study, we aimed to investigate whether studies published in orthodontic journals and titled as randomized clinical trials are truly randomized clinical trials. A second objective was to explore the association of journal type and other publication characteristics on correct classification. American Journal of Orthodontics and Dentofacial Orthopedics, European Journal of Orthodontics, Angle Orthodontist, Journal of Orthodontics, Orthodontics and Craniofacial Research, World Journal of Orthodontics, Australian Orthodontic Journal, and Journal of Orofacial Orthopedics were hand searched for clinical trials labeled in the title as randomized from 1979 to July 2011. The data were analyzed by using descriptive statistics, and univariable and multivariable examinations of statistical associations via ordinal logistic regression modeling (proportional odds model). One hundred twelve trials were identified. Of the included trials, 33 (29.5%) were randomized clinical trials, 52 (46.4%) had an unclear status, and 27 (24.1%) were not randomized clinical trials. In the multivariable analysis among the included journal types, year of publication, number of authors, multicenter trial, and involvement of statistician were significant predictors of correctly classifying a study as a randomized clinical trial vs unclear and not a randomized clinical trial. From 112 clinical trials in the orthodontic literature labeled as randomized clinical trials, only 29.5% were identified as randomized clinical trials based on clear descriptions of appropriate random number generation and allocation concealment. The type of journal, involvement of a statistician, multicenter trials, greater numbers of authors, and publication year were associated with correct clinical trial classification. This study indicates the need of clear and accurate reporting of clinical trials and the need for educating investigators on randomized clinical trial methodology. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. 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

The Use of Herbal Medicine in Alzheimer's Disease—A Systematic Review

PubMed Central

dos Santos-Neto, Leopoldo Luiz; de Vilhena Toledo, Maria Alice; Medeiros-Souza, Patrícia; de Souza, Gustavo Almeida

2006-01-01

The treatments of choice in Alzheimer's disease (AD) are cholinesterase inhibitors and NMDA-receptor antagonists, although doubts remain about the therapeutic effectiveness of these drugs. Herbal medicine products have been used in the treatment of Behavioral and Psychological Symptoms of Dementia (BPSD) but with various responses. The objective of this article was to review evidences from controlled studies in order to determine whether herbs can be useful in the treatment of cognitive disorders in the elderly. Randomized controlled studies assessing AD in individuals older than 65 years were identified through searches of MEDLINE, LILACS, Cochrane Library, dissertation Abstract (USA), ADEAR (Alzheimer's Disease Clinical Trials Database), National Research Register, Current Controlled trials, Centerwatch Trials Database and PsychINFO Journal Articles. The search combined the terms Alzheimer disease, dementia, cognition disorders, Herbal, Phytotherapy. The crossover results were evaluated by the Jadad's measurement scale. The systematic review identified two herbs and herbal formulations with therapeutic effects for the treatment of AD: Melissa officinalis, Salvia officinalis and Yi-Gan San and BDW (Ba Wei Di Huang Wan). Ginkgo biloba was identified in a meta-analysis study. All five herbs are useful for cognitive impairment of AD. M. officinalis and Yi-Gan San are also useful in agitation, for they have sedative effects. These herbs and formulations have demonstrated good therapeutic effectiveness but these results need to be compared with those of traditional drugs. Further large multicenter studies should be conducted in order to test the cost-effectiveness of these herbs for AD and the impact in the control of cognitive deterioration. PMID:17173107

The placebo effect and its determinants in fibromyalgia: meta-analysis of randomised controlled trials.

PubMed

Chen, Xi; Zou, Kun; Abdullah, Natasya; Whiteside, Nicola; Sarmanova, Aliya; Doherty, Michael; Zhang, Weiya

2017-07-01

The aims of this study were to determine whether placebo treatment in randomised controlled trials (RCTs) is effective for fibromyalgia and to identify possible determinants of the magnitude of any such placebo effect. A systematic literature search was undertaken for RCTs in people with fibromyalgia that included a placebo and/or a no-treatment (observation only or waiting list) control group. Placebo effect size (ES) for pain and other outcomes was measured as the improvement of each outcome from baseline divided by the standard deviation of the change from baseline. This effect was compared with changes in the no-treatment control groups. Meta-analysis was undertaken to combine data from different studies. Subgroup analysis was conducted to identify possible determinants of the placebo ES. A total of 3912 studies were identified from the literature search. After scrutiny, 229 trials met the inclusion criteria. Participants who received placebo in the RCTs experienced significantly better improvements in pain, fatigue, sleep quality, physical function, and other main outcomes than those receiving no treatment. The ES of placebo for pain relief was clinically moderate (0.53, 95%CI 0.48 to 0.57). The ES increased with increasing strength of the active treatment, increasing participant age and higher baseline pain severity, but decreased in RCTS with more women and with longer duration of fibromyalgia. In addition, placebo treatment in RCTs is effective in fibromyalgia. A number of factors (expected strength of treatment, age, gender, disease duration) appear to influence the magnitude of the placebo effect in this condition.

A survey of facilitators and barriers to recruitment to the MAGNETIC trial.

PubMed

Kaur, Geetinder; Smyth, Rosalind L; Powell, Colin V E; Williamson, Paula

2016-12-23

Recruitment to randomised controlled trials with children is challenging. It is imperative to understand the factors that boost or hinder recruitment of children to clinical trials. We conducted a survey of facilitators and barriers to recruitment to the MAGNETIC trial, using a previously developed web-based tool. MAGNETIC is a multicentre randomised trial of nebulised magnesium in acute severe asthma, recruiting 508 children from 30 UK sites. Recruiters were asked to grade a list of factors from -3 to +3 depending on whether the factor was perceived as a strong, intermediate or weak barrier (-3 to -1) or facilitator (+1 to + 3), and using (0) if it was thought to be not applicable. Free text responses were invited on strategies applied to counter the identified barriers. The commonly identified facilitators were motivation and experience of study teams, effective communication and coordination between teams at site and between sites and the Clinical Trials Unit, the presence of designated research nurses, good trial management, clinical trial publicity, simple inclusion criteria, effective communication with parents and presentation of trial information in a simple and clear manner. The commonly identified barriers were heavy clinical workload, shift patterns of work, Good Clinical Practice (GCP) training, inadequate number of trained staff, time and setting of consent seeking, non-availability of research staff out of hours and parents' concerns about their child taking an experimental medicine. Having a designated research nurse, arranging GCP training and trial-related training sessions for staff were the most commonly reported interventions. This study highlights important generic and trial-specific facilitators and barriers to recruitment to a paediatric trial in the acute setting and provides information on the recruitment strategies or interventions that were applied to overcome these barriers. This information can be very useful in informing the design and conduct of future clinical trials with children, particularly in the acute or emergency setting. ISRCTN, ISRCTN81456894 . Registered on 15 November 2007.

Variation in neurophysiological function and evidence of quantitative electroencephalogram discordance: predicting cocaine-dependent treatment attrition.

PubMed

Venneman, Sandy; Leuchter, Andrew; Bartzokis, George; Beckson, Mace; Simon, Sara L; Schaefer, Melodie; Rawson, Richard; Newton, Tom; Cook, Ian A; Uijtdehaage, Sebastian; Ling, Walter

2006-01-01

Cocaine treatment trials suffer from a high rate of attrition. We examined pretreatment neurophysiological factors to identify participants at greatest risk. Twenty-five participants were divided into concordant and discordant groups following electroencephalogram (EEG) measures recorded prior to a double-blind, placebo-controlled treatment trial. Three possible outcomes were examined: successful completion, dropout, and removal. Concordant (high perfusion correlate) participants had an 85% rate of successful completion, while discordant participants had a 15% rate of successful completion. Twenty-five percent of dropouts and 50% of participants removed were discordant (low perfusion correlate), while only 25% of those who completed were discordant. Failure to complete the trial was not explained by depression, craving, benzoylecgonine levels or quantitative electroencephalogram (QEEG) power; thus cordance may help identify attrition risk.

Tine cultivation effects on weed control, productivity, and economics of peanut under organic management

USDA-ARS?s Scientific Manuscript database

Identifying effective weed control regimes for organic peanut has become paramount for improving the feasibility of organic production. Tine cultivation is a proven effective method at reducing in-row weed populations in several crops. Field trials were therefore conducted in 2008 and 2009 to asse...

Cerebrovascular accidents in patients treated for choroidal neovascularization with ranibizumab in randomized controlled trials.

PubMed

Bressler, Neil M; Boyer, David S; Williams, David F; Butler, Steven; Francom, Steven F; Brown, Benton; Di Nucci, Flavia; Cramm, Timothy; Tuomi, Lisa L; Ianchulev, Tsontcho; Rubio, Roman G

2012-10-01

To analyze cerebrovascular accidents (CVAs) pooled from large, randomized, controlled clinical trials of ranibizumab treatment for neovascular age-related macular degeneration. Events in five trials (FOCUS, MARINA, ANCHOR, PIER, and SAILOR) were analyzed using a standard safety monitoring process. Exact methods, stratified by study, were used to test for treatment differences based on odds ratios. A stepwise logistic regression model was fit to classify subjects' risk for CVA based on medical history. Treatment differences in CVA rates at 1 year or 2 years were evaluated within risk groups using stratified exact methods. Pooled 2-year CVA rates were <3%; odds ratios (95% confidence intervals) for CVA risk were 1.2 (0.4-4.4) for ranibizumab 0.3-mg versus control, 2.2 (0.8-7.1) for 0.5 mg versus control, and 1.5 (0.8-3.0) for 0.5-mg versus 0.3-mg ranibizumab. No substantial increased risk of CVA for 0.5 mg versus 0.3 mg was identified in pooled analyses or any of the individual trials. In pooled analyses, the difference between 0.5-mg ranibizumab and control was larger (7.7 [1.2-177]) among high-risk CVA patients. This analysis provided some evidence, although not definitive, of a potential increased risk of CVA with ranibizumab versus control or with 0.5-mg versus 0.3-mg ranibizumab. Continued monitoring for CVA within clinical trials seems warrented.

The association of funding source on effect size in randomized controlled trials: 2013-2015 - a cross-sectional survey and meta-analysis.

PubMed

Falk Delgado, Alberto; Falk Delgado, Anna

2017-03-14

Trials financed by for-profit organizations have been associated with favorable outcomes of new treatments, although the effect size of funding source impact on outcome is unknown. The aim of this study was to estimate the effect size for a favorable outcome in randomized controlled trials (RCTs), stratified by funding source, that have been published in general medical journals. Parallel-group RCTs published in The Lancet, New England Journal of Medicine, and JAMA between 2013 and 2015 were identified. RCTs with binary primary endpoints were included. The primary outcome was the OR of patients' having a favorable outcome in the intervention group compared with the control group. The OR of a favorable outcome in each trial was calculated by the number of positive events that occurred in the intervention and control groups. A meta-analytic technique with random effects model was used to calculate summary OR. Data were stratified by funding source as for-profit, mixed, and nonprofit. Prespecified sensitivity, subgroup, and metaregression analyses were performed. Five hundred nine trials were included. The OR for a favorable outcome in for-profit-funded RCTs was 1.92 (95% CI 1.72-2.14), which was higher than mixed source-funded RCTs (OR 1.34, 95% CI 1.25-1.43) and nonprofit-funded RCTs (OR 1.32, 95% CI 1.26-1.39). The OR for a favorable outcome was higher for both clinical and surrogate endpoints in for-profit-funded trials than in RCTs with other funding sources. Excluding drug trials lowered the OR for a favorable outcome in for-profit-funded RCTs. The OR for a favorable surrogate outcome in drug trials was higher in for-profit-funded trials than in nonprofit-funded trials. For-profit-funded RCTs have a higher OR for a favorable outcome than nonprofit- and mixed source-funded RCTs. This difference is associated mainly with the use of surrogate endpoints in for-profit-financed drug trials.

Randomized Trial of a Web-Based Intervention to Address Barriers to Clinical Trials.

PubMed

Meropol, Neal J; Wong, Yu-Ning; Albrecht, Terrance; Manne, Sharon; Miller, Suzanne M; Flamm, Anne Lederman; Benson, Al Bowen; Buzaglo, Joanne; Collins, Michael; Egleston, Brian; Fleisher, Linda; Katz, Michael; Kinzy, Tyler G; Liu, Tasnuva M; Margevicius, Seunghee; Miller, Dawn M; Poole, David; Roach, Nancy; Ross, Eric; Schluchter, Mark D

2016-02-10

Lack of knowledge and negative attitudes have been identified as barriers to participation in clinical trials by patients with cancer. We developed Preparatory Education About Clinical Trials (PRE-ACT), a theory-guided, Web-based, interactive computer program, to deliver tailored video educational content to patients in an effort to overcome barriers to considering clinical trials as a treatment option. A prospective, randomized clinical trial compared PRE-ACT with a control condition that provided general clinical trials information produced by the National Cancer Institute (NCI) in text format. One thousand two hundred fifty-five patients with cancer were randomly allocated before their initial visit with an oncologist to PRE-ACT (n = 623) or control (n = 632). PRE-ACT had three main components: assessment of clinical trials knowledge and attitudinal barriers, values assessment with clarification back to patients, and provision of a video library tailored to address each patient's barriers. Outcomes included knowledge and attitudes and preparation for decision making about clinical trials. Both PRE-ACT and control interventions improved knowledge and attitudes (all P < .001) compared with baseline. Patients randomly allocated to PRE-ACT showed a significantly greater increase in knowledge (P < .001) and a significantly greater decrease in attitudinal barriers (P < .001) than did their control (text-only) counterparts. Participants in both arms significantly increased their preparedness to consider clinical trials (P < .001), and there was a trend favoring the PRE-ACT group (P < .09). PRE-ACT was also associated with greater patient satisfaction than was NCI text alone. These data show that patient education before the first oncologist visit improves knowledge, attitudes, and preparation for decision making about clinical trials. Both text and tailored video were effective. The PRE-ACT interactive video program was more effective than NCI text in improving knowledge and reducing attitudinal barriers. © 2015 by American Society of Clinical Oncology.

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.

Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. Methods and design This will be an open-label randomized, controlled trial conducted at Women’s College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the ‘multiple comparisons with the best’ approach for data analyses, as this strategy allows practical considerations of ease of use and tolerability to guide selection of the preparation for future studies. Discussion Data from this protocol will be used to develop a randomized, controlled trial of nitrates to prevent osteoporotic fractures. Trial registration ClinicalTrials.gov Identifier: NCT01387672. Controlled-Trials.com: ISRCTN08860742. PMID:24010992

Benefit and harm of adding ketamine to an opioid in a patient-controlled analgesia device for the control of postoperative pain: systematic review and meta-analyses of randomized controlled trials with trial sequential analyses.

PubMed

Assouline, Benjamin; Tramèr, Martin R; Kreienbühl, Lukas; Elia, Nadia

2016-12-01

Ketamine is often added to opioids in patient-controlled analgesia devices. We tested whether in surgical patients, ketamine added to an opioid patient-controlled analgesia decreased pain intensity by ≥25%, cumulative opioid consumption by ≥30%, the risk of postoperative nausea and vomiting by ≥30%, the risk of respiratory adverse effects by ≥50%, and increased the risk of hallucination not more than 2-fold. In addition, we searched for evidence of dose-responsiveness. Nineteen randomized trials (1349 adults, 104 children) testing different ketamine regimens added to various opioids were identified through searches in databases and bibliographies (to 04.2016). In 9 trials (595 patients), pain intensity at rest at 24 hours was decreased by 32% with ketamine (weighted mean difference -1.1 cm on the 0-10 cm visual analog scale [98% CI, -1.8 to -0.39], P < 0.001). In 7 trials (495 patients), cumulative 24 hours morphine consumption was decreased by 28% with ketamine (weighted mean difference -12.9 mg [-22.4 to -3.35], P = 0.002). In 7 trials (435 patients), the incidence of postoperative nausea and vomiting was decreased by 44% with ketamine (risk ratio 0.56 [0.40 to 0.78], P < 0.001). There was no evidence of a difference in the incidence of respiratory adverse events (9 trials, 871 patients; risk ratio 0.31 [0.06 to 1.51], P = 0.08) or hallucination (7 trials, 690 patients; odds ratio 1.16 [0.47 to 2.79], P = 0.70). Trial sequential analyses confirmed the significant benefit of ketamine on pain intensity, cumulative morphine consumption, and postoperative nausea and vomiting and its inability to double the risk of hallucination. The available data did not allow us to make a conclusion on respiratory adverse events or to establish dose-responsiveness.

Corticosteroids as adjuvant therapy for ocular toxoplasmosis.

PubMed

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

2017-01-26

Ocular infection caused by 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 to anti-parasitic therapy versus anti-parasitic therapy alone for ocular toxoplasmosis. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register (2016; Issue 11)), MEDLINE Ovid, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE Ovid Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Literature on Health Sciences (LILACS (January 1982 to December 2016)), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), 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 7 December 2016. We had 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 acute ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, different doses or times of initiation of corticosteroids. Two authors independently screened titles and abstracts retrieved through the electronic searches. We retrieved full-text reports of studies categorized as 'unsure' or 'include' after we reviewed the abstracts. Two authors independently reviewed each full-text report for eligibility. Discrepancies were resolved through discussion. We identified no completed or ongoing trial that was eligible for this Cochrane review. Although research has identified a wide variation in practice regarding the use of corticosteroids, our review did not identify any evidence from randomized controlled trials for or against the role of corticosteroids in the management of ocular toxoplasmosis. Several questions remain unanswered by well-conducted randomized trials in this context, including whether the use of corticosteroids as an adjunctive agent is more effective than the use of anti-parasitic therapy alone; if so, when corticosteroids should be initiated in the treatment regimen (early versus late course of treatment), and what would be the best dose and duration of steroid use.

Corticosteroids as adjuvant therapy for ocular toxoplasmosis

PubMed Central

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

2017-01-01

Background Ocular infection caused by 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 to anti-parasitic therapy versus anti-parasitic therapy alone for ocular toxoplasmosis. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register (2016; Issue 11)), MEDLINE Ovid, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE Ovid Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Literature on Health Sciences (LILACS (January 1982 to December 2016)), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), 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 7 December 2016. Selection criteria We had 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 acute ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, different doses or times of initiation of corticosteroids. Data collection and analysis Two authors independently screened titles and abstracts retrieved through the electronic searches. We retrieved full-text reports of studies categorized as ’unsure’ or ’include’ after we reviewed the abstracts. Two authors independently reviewed each full-text report for eligibility. Discrepancies were resolved through discussion. Main results We identified no completed or ongoing trial that was eligible for this Cochrane review. Authors’ conclusions Although research has identified a wide variation in practice regarding the use of corticosteroids, our review did not identify any evidence from randomized controlled trials for or against the role of corticosteroids in the management of ocular toxoplasmosis. Several questions remain unanswered by well-conducted randomized trials in this context, including whether the use of corticosteroids as an adjunctive agent is more effective than the use of anti-parasitic therapy alone; if so, when corticosteroids should be initiated in the treatment regimen (early versus late course of treatment), and what would be the best dose and duration of steroid use. PMID:28125765

Update to a protocol for a feasibility cluster randomised controlled trial of a peer-led school-based intervention to increase the physical activity of adolescent girls (PLAN-A).

PubMed

Sebire, Simon J; Edwards, Mark J; Campbell, Rona; Jago, Russell; Kipping, Ruth; Banfield, Kathryn; Kadir, Bryar; Garfield, Kirsty; Lyons, Ronan A; Blair, Peter S; Hollingworth, William

2016-01-01

Physical activity levels are low amongst adolescent girls, and this population faces specific barriers to being active. Peer influences on health behaviours are important in adolescence, and peer-led interventions might hold promise to change behaviour. This paper describes the protocol for a feasibility cluster randomised controlled trial of Peer-Led physical Activity iNtervention for Adolescent girls (PLAN-A), a peer-led intervention aimed at increasing adolescent girls' physical activity levels. In addition, this paper describes an update that has been made to the protocol for the PLAN-A feasibility cluster randomised controlled trial. A two-arm cluster randomised feasibility trial will be conducted in six secondary schools (intervention n  = 4; control n  = 2) with year 8 (12-13 years old) girls. The intervention will operate at a year group level and consist of year 8 girls nominating influential peers within their year group to become peer supporters. Approximately 15% of the cohort will receive 3 days of training about physical activity and interpersonal communication skills. Peer supporters will then informally diffuse messages about physical activity amongst their friends for 10 weeks. Data will be collected at baseline (time 0 (T0)), immediately after the intervention (time 1 (T1)) and 12 months after baseline measures (time 2 (T2)). In this feasibility trial, the primary interest is in the recruitment of schools and participants (both year 8 girls and peer supporters), delivery and receipt of the intervention, data provision rates and identifying the cost categories for future economic analysis. Physical activity will be assessed using 7-day accelerometry, with the likely primary outcome in a fully powered trial being daily minutes of moderate-to-vigorous physical activity. Participants will also complete psychosocial questionnaires at each time point: assessing motivation, self-esteem and peer physical activity norms. Data analysis will be largely descriptive and focus on recruitment, attendance and data provision rates. The findings will inform the sample size required for a definitive trial. A detailed process evaluation using qualitative and quantitative methods will be conducted with a variety of stakeholders (i.e. pupils, parents, teachers and peer-supporter trainers) to identify areas of success and necessary improvements prior to proceeding to a definitive trial. The study will provide the information necessary to design a fully powered trial should PLAN-A demonstrate evidence of promise. This paper describes an update to the protocol for the PLAN-A feasibility cluster randomised controlled trial related to the data-linkage component. ISRCTN12543546.

Telehealthcare for chronic obstructive pulmonary disease: Cochrane Review and meta-analysis

PubMed Central

McLean, Susannah; Nurmatov, Ulugbek; Liu, Joseph LY; Pagliari, Claudia; Car, Josip; Sheikh, Aziz

2012-01-01

Background Chronic obstructive pulmonary disease (COPD) is common. Telehealthcare, involving personalised health care over a distance, is seen as having the potential to improve care for people with COPD. Aim To systematically review the effectiveness of telehealthcare interventions in COPD to improve clinical and process outcomes. Design and setting Cochrane Systematic Review of randomised controlled trials. Methods The study involved searching the Cochrane Airways Group Register of Trials, which is derived from the Cochrane Central Register of Controlled Trials, MEDLINE®, embase™, and CINAHL®, as well as searching registers of ongoing and unpublished trials. Randomised controlled trials comparing a telehealthcare intervention with a control intervention in people with a clinical diagnosis of COPD were identified. The main outcomes of interest were quality of life and risk of emergency department visit, hospitalisation, and death. Two authors independently selected trials for inclusion and extracted data. Study quality was assessed using the Cochrane Collaboration’s risk of bias method. Meta-analysis was undertaken using fixed effect and/or random effects modelling. Results Ten randomised controlled trials were included. Telehealthcare did not improve COPD quality of life: mean difference –6.57 (95% confidence interval [CI] = –13.62 to 0.48). However, there was a significant reduction in the odds ratios (ORs) of emergency department attendance (OR = 0.27; 95% CI = 0.11 to 0.66) and hospitalisation (OR = 0.46; 95% CI = 0.33 to 0.65). There was a non-significant change in the OR of death (OR = 1.05; 95% CI = 0.63 to 1.75). Conclusion In COPD, telehealthcare interventions can significantly reduce the risk of emergency department attendance and hospitalisation, but has little effect on the risk of death. PMID:23211177

Interventions for increasing fruit and vegetable consumption in children aged five years and under.

PubMed

Hodder, Rebecca K; Stacey, Fiona G; O'Brien, Kate M; Wyse, Rebecca J; Clinton-McHarg, Tara; Tzelepis, Flora; James, Erica L; Bartlem, Kate M; Nathan, Nicole K; Sutherland, Rachel; Robson, Emma; Yoong, Sze Lin; Wolfenden, Luke

2018-01-25

Insufficient consumption of fruits and vegetables in childhood increases the risk of future chronic diseases, including cardiovascular disease. To assess the effectiveness, cost effectiveness and associated adverse events of interventions designed to increase the consumption of fruit, vegetables or both amongst children aged five years and under. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and Embase to identify eligible trials on 25 September 2017. We searched Proquest Dissertations and Theses and two clinical trial registers in November 2017. We reviewed reference lists of included trials and handsearched three international nutrition journals. We contacted authors of included studies to identify further potentially relevant trials. We included randomised controlled trials, including cluster-randomised controlled trials and cross-over trials, of any intervention primarily targeting consumption of fruit, vegetables or both among children aged five years and under, and incorporating a dietary or biochemical assessment of fruit or vegetable consumption. Two review authors independently screened titles and abstracts of identified papers; a third review author resolved disagreements. Two review authors independently extracted data and assessed the risks of bias of included studies; a third review author resolved disagreements. Due to unexplained heterogeneity, we used random-effects models in meta-analyses for the primary review outcomes where we identified sufficient trials. We calculated standardised mean differences (SMDs) to account for the heterogeneity of fruit and vegetable consumption measures. We conducted assessments of risks of bias and evaluated the quality of evidence (GRADE approach) using Cochrane procedures. We included 55 trials with 154 trial arms and 11,108 participants. Thirty-three trials examined the impact of child-feeding practices (e.g. repeated food exposure) in increasing child vegetable intake. Thirteen trials examined the impact of parent nutrition education in increasing child fruit and vegetable intake. Eight studies examined the impact of multicomponent interventions (e.g. parent nutrition education and preschool policy changes) in increasing child fruit and vegetable intake. One study examined the effect of a nutrition intervention delivered to children in increasing child fruit and vegetable intake.We judged 14 of the 55 included trials as free from high risks of bias across all domains; performance, detection and attrition bias were the most common domains judged at high risk of bias for the remaining studies.Meta-analysis of trials examining child-feeding practices versus no intervention revealed a positive effect on child vegetable consumption (SMD 0.38, 95% confidence interval (CI) 0.15 to 0.61; n = 1509; 11 studies; very low-quality evidence), equivalent to a mean difference of 4.03 g of vegetables. There were no short-term differences in child consumption of fruit and vegetables in meta-analyses of trials examining parent nutrition education versus no intervention (SMD 0.11, 95% CI -0.05 to 0.28; n = 3023; 10 studies; very low-quality evidence) or multicomponent interventions versus no intervention (SMD 0.28, 95% CI -0.06 to 0.63; n = 1861; 4 studies; very low-quality evidence).Insufficient data were available to assess long-term effectiveness, cost effectiveness and unintended adverse consequences of interventions. Studies reported receiving governmental or charitable funds, except for three studies reporting industry funding. Despite identifying 55 eligible trials of various intervention approaches, the evidence for how to increase children's fruit and vegetable consumption remains sparse. There was very low-quality evidence that child-feeding practice interventions are effective in increasing vegetable consumption in children aged five years and younger, however the effect size was very small and long-term follow-up is required. There was very low-quality evidence that parent nutrition education and multicomponent interventions are not effective in increasing fruit and vegetable consumption in children aged five years and younger. All findings should be considered with caution, given most included trials could not be combined in meta-analyses. Given the very low-quality evidence, future research will very likely change estimates and conclusions. Such research should adopt more rigorous methods to advance the field.This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Deliberate self harm: systematic review of efficacy of psychosocial and pharmacological treatments in preventing repetition

PubMed Central

Hawton, Keith; Arensman, Ella; Townsend, Ellen; Bremner, Sandy; Feldman, Eleanor; Goldney, Robert; Gunnell, David; Hazell, Philip; van Heeringen, Kees; House, Allan; Owens, David; Sakinofsky, Isaac; Träskman-Bendz, Lil

1998-01-01

Objective: To identify and synthesise the findings from all randomised controlled trials that have examined the effectiveness of treatments of patients who have deliberately harmed themselves. Design: Systematic review of randomised controlled trials of psychosocial and physical treatments. Studies categorised according to type of treatment. When there was more than one investigation in a particular category a summary odds ratio was estimated with the Mantel-Haenszel method. Setting: Randomised trials available in electronic databases in 1996, in the Cochrane Controlled Trials Register in 1997, and from hand searching of journals to 1997. Subjects: Patients who had deliberately harmed themselves shortly before entry into the trials with information on repetition of behaviour. The included trials comprised 2452 randomised participants with outcome data. Main outcome measure: Repetition of self harm. Results: 20 trials reported repetition of self harm as an outcome variable, classified into 10 categories. Summary odds ratio (all for comparison with standard aftercare) indicated reduced repetition for problem solving therapy (0.73; 95% confidence interval 0.45 to 1.18) and for provision of an emergency contact card in addition to standard care (0.45; 0.19 to 1.07). The summary odds ratios were 0.83 (0.61 to 1.14) for trials of intensive aftercare plus outreach and 1.19 (0.53 to 2.67) for antidepressant treatment compared with placebo. Significantly reduced rates of further self harm were observed for depot flupenthixol versus placebo in multiple repeaters (0.09; 0.02 to 0.50) and for dialectical behaviour therapy versus standard aftercare (0.24; 0.06 to 0.93). Conclusion: There remains considerable uncertainty about which forms of psychosocial and physical treatments of patients who harm themselves are most effective. Further larger trials of treatments are needed. Key messages A systematic review of the effectiveness of psychosocial and drug treatments of patients who deliberately harm themselves identified 20 randomised controlled trials in which repetition of self harm was reported as an outcome Promising results were found for problem solving therapy, provision of a card to allow patients to make emergency contact with services, depot flupenthixol for recurrent self harm, and long term psychological therapy for female patients with borderline personality disorder and recurrent self harm Assertive outreach can help to keep patients in treatment Nearly all the trials included too few patients to detect clinically significant differences in repetition of self harm, and even synthesis of results by meta-analysis did not have the power to detect such differences There is an urgent need for large trials of promising therapies for this substantial clinical population PMID:9703526

Participant experiences of an internet-based intervention and randomised control trial: interview study

PubMed Central

2013-01-01

Background There are an increasing number of interventions being delivered online, and an expanding body of research to assess the effectiveness of such interventions. Yet, little is known about the motivations for participating in online research. Furthermore, internet interventions and online research studies are characterised by poor adherence and high attrition rates. This study aimed to explore participant motivations for taking part in an online trial of an internet intervention and the reasons for continuing. Methods Semi-structured telephone interviews were conducted with twenty members of the intervention arm of an internet-based randomised control trial evaluating an online cognitive behavioural tool to improve mental wellbeing. The qualitative interviews were analysed using the Framework Approach to identify themes and subthemes, through familiarization with the data, identifying a thematic framework, charting, indexing, mapping and interpreting the data. Results A number of key themes emerged. Trusted brands were key to participants feeling secure in engaging with the trial due to the association with institutions such as the UK National Health Service and the lead University conducting the research. Participants had a number of motivations for signing up with the study; altruism, low mood and as a replacement for a physical health professional. Participants felt the need for the language used in the intervention to be tailored to them as individuals. The majority of those interviewed also described multiple benefits from the intervention, which could have been a reason for them to persist. Conclusion The nascent field of research on internet delivered healthcare needs to take account of participant views, as have been identified in this trial and future studies would benefit from applying its findings. PMID:24165325

Systematic review of randomised controlled trials of interventions that aim to reduce the risk, either directly or indirectly, of overweight and obesity in infancy and early childhood

PubMed Central

Edmonds, Barrie; Swift, Judy Anne; Siriwardena, Aloysius Niroshan; Weng, Stephen; Nathan, Dilip; Glazebrook, Cris

2016-01-01

Abstract The risk factors for childhood overweight and obesity are known and can be identified antenatally or during infancy, however, the majority of effective interventions are designed for older children. This review identified interventions designed to reduce the risk of overweight/obesity that were delivered antenatally or during the first 2 years of life, with outcomes reported from birth to 7 years of age. Six electronic databases were searched for papers reporting randomised controlled trials of interventions published from January 1990 to September 2013. A total of 35 eligible studies were identified, describing 27 unique trials of which 24 were behavioural and three were non‐behavioural. The 24 behavioural trials were categorised by type of intervention: (1) nutritional and/or responsive feeding interventions targeted at parents of infants, which improved feeding practices and had some impact on child weight (n = 12); (2) breastfeeding promotion and lactation support for mothers, which had a positive effect on breastfeeding but not child weight (n = 5); (3) parenting and family lifestyle (n = 4); and (4) maternal health (n = 3) interventions that had some impact on feeding practices but not child weight. The non‐behavioural trials comprised interventions manipulating formula milk composition (n = 3). Of these, lower/hydrolysed protein formula milk had a positive effect on weight outcomes. Interventions that aim to improve diet and parental responsiveness to infant cues showed most promise in terms of self‐reported behavioural change. Despite the known risk factors, there were very few intervention studies for pregnant women that continue during infancy which should be a priority for future research. PMID:25894857

Patient-reported outcomes in randomised controlled trials of colorectal cancer: an analysis determining the availability of robust data to inform clinical decision-making

PubMed Central

Whale, Katie; Fish, Daniel; Fayers, Peter; Cafaro, Valentina; Pusic, Andrea; Blazeby, Jane M.; Efficace, Fabio

2016-01-01

Purpose Randomised controlled trials (RCTs) are the most robust study design measuring outcomes of colorectal cancer (CRC) treatments, but to influence clinical practice trial design and reporting of patient-reported outcomes (PROs) must be of high quality. Objectives of this study were as follows: to examine the quality of PRO reporting in RCTs of CRC treatment; to assess the availability of robust data to inform clinical decision-making; and to investigate whether quality of reporting improved over time. Methods A systematic review from January 2004–February 2012 identified RCTs of CRC treatment describing PROs. Relevant abstracts were screened and manuscripts obtained. Methodological quality was assessed using International Society for Quality of Life Research—patient-reported outcome reporting standards. Changes in reporting quality over time were established by comparison with previous data, and risk of bias was assessed with the Cochrane risk of bias tool. Results Sixty-six RCTs were identified, seven studies (10 %) reported survival benefit favouring the experimental treatment, 35 trials (53 %) identified differences in PROs between treatment groups, and the clinical significance of these differences was discussed in 19 studies (29 %). The most commonly reported treatment type was chemotherapy (n = 45; 68 %). Improvements over time in key methodological issues including the documentation of missing data and the discussion of the clinical significance of PROs were found. Thirteen trials (20 %) had high-quality reporting. Conclusions Whilst improvements in PRO quality reporting over time were found, several recent studies still fail to robustly inform clinical practice. Quality of PRO reporting must continue to improve to maximise the clinical impact of PRO findings. PMID:25910987

Systematic review of randomised controlled trials of interventions that aim to reduce the risk, either directly or indirectly, of overweight and obesity in infancy and early childhood.

PubMed

Redsell, Sarah A; Edmonds, Barrie; Swift, Judy Anne; Siriwardena, Aloysius Niroshan; Weng, Stephen; Nathan, Dilip; Glazebrook, Cris

2016-01-01

The risk factors for childhood overweight and obesity are known and can be identified antenatally or during infancy, however, the majority of effective interventions are designed for older children. This review identified interventions designed to reduce the risk of overweight/obesity that were delivered antenatally or during the first 2 years of life, with outcomes reported from birth to 7 years of age. Six electronic databases were searched for papers reporting randomised controlled trials of interventions published from January 1990 to September 2013. A total of 35 eligible studies were identified, describing 27 unique trials of which 24 were behavioural and three were non-behavioural. The 24 behavioural trials were categorised by type of intervention: (1) nutritional and/or responsive feeding interventions targeted at parents of infants, which improved feeding practices and had some impact on child weight (n = 12); (2) breastfeeding promotion and lactation support for mothers, which had a positive effect on breastfeeding but not child weight (n = 5); (3) parenting and family lifestyle (n = 4); and (4) maternal health (n = 3) interventions that had some impact on feeding practices but not child weight. The non-behavioural trials comprised interventions manipulating formula milk composition (n = 3). Of these, lower/hydrolysed protein formula milk had a positive effect on weight outcomes. Interventions that aim to improve diet and parental responsiveness to infant cues showed most promise in terms of self-reported behavioural change. Despite the known risk factors, there were very few intervention studies for pregnant women that continue during infancy which should be a priority for future research. © 2015 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.

Efficacy of group psychotherapy for social anxiety disorder: A meta-analysis of randomized-controlled trials.

PubMed

Barkowski, Sarah; Schwartze, Dominique; Strauss, Bernhard; Burlingame, Gary M; Barth, Jürgen; Rosendahl, Jenny

2016-04-01

Group psychotherapy for social anxiety disorder (SAD) is an established treatment supported by findings from primary studies and earlier meta-analyses. However, a comprehensive summary of the recent evidence is still pending. This meta-analysis investigates the efficacy of group psychotherapy for adult patients with SAD. A literature search identified 36 randomized-controlled trials examining 2171 patients. Available studies used mainly cognitive-behavioral group therapies (CBGT); therefore, quantitative analyses were done for CBGT. Medium to large positive effects emerged for wait list-controlled trials for specific symptomatology: g=0.84, 95% CI [0.72; 0.97] and general psychopathology: g=0.62, 95% CI [0.36; 0.89]. Group psychotherapy was also superior to common factor control conditions in alleviating symptoms of SAD, but not in improving general psychopathology. No differences appeared for direct comparisons of group psychotherapy and individual psychotherapy or pharmacotherapy. Hence, group psychotherapy for SAD is an efficacious treatment, equivalent to other treatment formats. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluating the design and reporting of pragmatic trials in osteoarthritis research.

PubMed

Ali, Shabana Amanda; Kloseck, Marita; Lee, Karen; Walsh, Kathleen Ellen; MacDermid, Joy C; Fitzsimmons, Deborah

2018-01-01

Among the challenges in health research is translating interventions from controlled experimental settings to clinical and community settings where chronic disease is managed daily. Pragmatic trials offer a method for testing interventions in real-world settings but are seldom used in OA research. The aim of this study was to evaluate the literature on pragmatic trials in OA research up to August 2016 in order to identify strengths and weaknesses in the design and reporting of these trials. We used established guidelines to assess the degree to which 61 OA studies complied with pragmatic trial design and reporting. We assessed design according to the pragmatic-explanatory continuum indicator summary and reporting according to the pragmatic trials extension of the CONsolidated Standards of Reporting Trials guidelines. None of the pragmatic trials met all 11 criteria evaluated and most of the trials met between 5 and 8 of the criteria. Criteria most often unmet pertained to practitioner expertise (by requiring specialists) and criteria most often met pertained to primary outcome analysis (by using intention-to-treat analysis). Our results suggest a lack of highly pragmatic trials in OA research. We identify this as a point of opportunity to improve research translation, since optimizing the design and reporting of pragmatic trials can facilitate implementation of evidence-based interventions for OA care. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Anti-inflammatory drugs and analgesics for managing symptoms in people with cystic fibrosis-related arthritis.

PubMed

Thornton, Judith; Rangaraj, Satyapal

2016-01-21

Arthritis remains a relatively infrequent complication of cystic fibrosis, but is a cause of significant morbidity when it does occur. Two distinct types of arthritis are described in cystic fibrosis: cystic fibrosis-related arthropathy (CFA) and hypertrophic pulmonary osteoarthropathy (HPO). Management of arthritis in people with cystic fibrosis is uncertain and complex because of the underlying disease and its intense treatment. This is an update of a previously published review. To review the effectiveness and safety of pharmacological agents for the symptomatic management of cystic fibrosis-related arthritis in adults and children with cystic fibrosis. 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.Date of most recent search: 19 January 2016. Randomised controlled studies which compared the efficacy and safety of anti-inflammatory and analgesic agents (e.g. non-steroidal anti-inflammatory agents, systemic corticosteroids, intra-articular corticosteroids) with each other, with no treatment or with placebo for CFA and HPO. No relevant studies were identified. No studies were included in this review. Although it is generally recognised that CFA may be episodic and resolve spontaneously, treatment with analgesics and anti-inflammatory agents may be needed. While this approach may be sufficient to manage symptoms, it is disappointing that no randomised controlled trials to rigorously evaluate these agents were found, nor could the authors identify any quasi-randomised. This systematic review has identified the need for a well-designed adequately-powered randomised controlled trial to assess the efficacy and safety of pharmacological agents for the symptomatic management of cystic fibrosis-related arthritis (CFA and HPO) in adults and children with cystic fibrosis. Studies should also better define the two conditions. A study has recently been conducted in CFA and may help fill this gap when analysed and published.There are no trials included in the review up to January 2016. We will continue to run searches to identify any potentially relevant studies; however, we do not plan to update other sections of the review until new studies are published.

Rationale and design of the ENhancing outcomes through Goal Assessment and Generating Engagement in Diabetes Mellitus (ENGAGE-DM) pragmatic trial.

PubMed

Lauffenburger, Julie C; Lewey, Jennifer; Jan, Saira; Nanchanatt, Gina; Makanji, Sagar; Ferro, Christina A; Sheehan, John; Wittbrodt, Eric; Morawski, Kyle; Lee, Jessica; Ghazinouri, Roya; Choudhry, Niteesh K

2017-08-01

Poor glycemic control among patients with diabetes may stem from poor medication and lifestyle adherence or a failure to appropriately intensify therapy. A patient-centered approach could discern the most likely possibility and would then, as appropriate, address patient barriers to non-adherence (using behavioral interviewing methods such as motivational interviewing) or help facilitate choices among treatment augmentation options (using methods such as shared decision-making). To test the impact of a novel telephone-based patient-centered intervention on glycemic control for patients with poorly-controlled diabetes. ENGAGE-DM (ENhancing outcomes through Goal Assessment and Generating Engagement in Diabetes Mellitus) is a pragmatic trial of patients with poorly-controlled diabetes receiving treatment with an oral hypoglycemic agent. We randomized 1400 patients in a large health insurer to intervention or usual care. The intervention is delivered over the telephone by a pharmacist and consists of a 2-step process that integrates brief negotiated interviewing and shared decision-making to identify patient-concordant goals and options for enhancing patients' diabetes management. The trial's primary outcome is disease control, assessed using glycosylated hemoglobin values. Secondary outcomes include medication adherence measures, assessed using pharmacy claims data. This trial will determine whether a novel highly-scalable patient engagement strategy improves disease control and adherence to medications among individuals with poorly-controlled diabetes. Copyright © 2017. Published by Elsevier Inc.

Enhancing response inhibition by incentive: Comparison of adolescents with and without substance use disorder

PubMed Central

Chung, Tammy; Geier, Charles; Luna, Beatriz; Pajtek, Stefan; Terwilliger, Robert; Thatcher, Dawn; Clark, Duncan

2010-01-01

Effective response inhibition is a key component of recovery from addiction. Some research suggests that response inhibition can be enhanced through reward contingencies. We examined the effect of monetary incentive on response inhibition among adolescents with and without substance use disorder (SUD) using a fast event-related fMRI antisaccade reward task. The fMRI task permits investigation of how reward (monetary incentive) might modulate inhibitory control during three task phases: cue presentation (reward or neutral trial), response preparation, and response execution. Adolescents with lifetime SUD (n=12; 100% marijuana use disorder) were gender and age-matched to healthy controls (n=12). Monetary incentive facilitated inhibitory control for SUD adolescents; for healthy controls, the difference in error rate for neutral and reward trials was not significant. There were no significant differences in behavioral performance between groups across reward and neutral trials, however, group differences in regional brain activation were identified. During the response preparation phase of reward trials, SUD adolescents, compared to controls, showed increased activation of prefrontal and oculomotor control (e.g., frontal eye field) areas, brain regions that have been associated with effective response inhibition. Results indicate differences in brain activation between SUD and control youth when preparing to inhibit a prepotent response in the context of reward, and support a possible role for incentives in enhancing response inhibition among youth with SUD. PMID:21115229

Women's experiences as members of attention control and experimental intervention groups in a randomized controlled trial.

PubMed

Beal, Claudia C; Stuifbergen, Alexa; Volker, Deborah; Becker, Heather

2009-12-01

Attention control groups are often used in research testing the efficacy of psychosocial and behavioural interventions in order to control for placebo effects. The authors conducted a descriptive qualitative study to investigate how participants viewed their experiences in attention control and experimental intervention groups following a randomized controlled trial for women with fibromyalgia syndrome. Moderately structured interviews were conducted with 18 women (12 from the experimental intervention group and 6 from the attention control group). Members of the control group reported some benefits but few behavioural changes as a result of participating in the RCT, and some participants expressed disappointment at not receiving the intervention. Perceptions of changes in attitudes towards fibromyalgia syndrome and behaviours reported by the intervention group appear to be consistent with the theory underlying the intervention. Possible placebo effects identified in both groups include negative and positive social interactions with other participants.

Clinical efficacy of composite versus ceramic inlays and onlays: a systematic review.

PubMed

Fron Chabouis, Hélène; Smail Faugeron, Violaine; Attal, Jean-Pierre

2013-12-01

Large tooth substance losses are frequent in posterior teeth because of primary caries or aging restorations. Inlays and onlays are often the minimal invasive solution in such cases, but the efficacy of the composite and ceramic materials used is unknown. We performed a systematic review of randomized controlled trials comparing the efficacy of composite and ceramic inlays or onlays. MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched without any restriction on date or language, as were references of eligible studies and ClinicalTrials.gov. Eligible studies were randomized trials comparing the clinical efficacy of composite to ceramic inlays or onlays in adults with any clinical outcome for at least 6 months. From 172 records identified, we examined reports of 2 randomized controlled trials involving 138 inlays (no onlays evaluated) in 80 patients and exhibiting a high-risk of bias. Outcomes were clinical scores and major failures. The 3-year overall failure risk ratio was 2 [0.38-10.55] in favor of ceramic inlays although not statistically significant. The reported clinical scores (United States Public Health Services and Californian Dental Association) showed considerable heterogeneity between trials and could not be combined. We have very limited evidence that ceramics perform better than composite material for inlays in the short term. However, this result may not be valid in the long term, and other trials are needed. Trials should follow Fédération dentaire internationale recommendations and enhance their methodology. Trials comparing composite and ceramic onlays are needed. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Benefits of commercial weight-loss programs on blood pressure and lipids: a systematic review.

PubMed

Mehta, Ambereen K; Doshi, Ruchi S; Chaudhry, Zoobia W; Jacobs, David K; Vakil, Rachit M; Lee, Clare J; Bleich, Sara N; Clark, Jeanne M; Gudzune, Kimberly A

2016-09-01

Our objective was to compare the effect of commercial weight-loss programs on blood pressure and lipids to control/education or counseling among individuals with overweight/obesity. We conducted a systematic review by searching MEDLINE and Cochrane Database of Systematic Reviews from inception to November 2014 and references identified by the programs. We included randomized, controlled trials ≥12weeks in duration. Two reviewers extracted information on study design, interventions, and mean change in systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglycerides, and total cholesterol and assessed risk of bias. We included 27 trials. Participants' blood pressure and lipids were normal at baseline in most trials. At 12months, Weight Watchers showed little change in blood pressure or lipid outcomes as compared to control/education (2 trials). At 12months, Atkins' participants had higher HDL-c and lower triglycerides than counseling (4 trials). Other programs had inconsistent effects or lacked long-term studies. Risk of bias was high for most trials of all programs. In conclusion, limited data exist regarding most commercial weight-loss programs' long-term effects on blood pressure and lipids. Clinicians should be aware that Weight Watchers has limited data that demonstrate CVD risk factor benefits relative to control/education. Atkins may be a reasonable option for patients with dyslipidemia. Additional well-designed, long-term trials are needed to confirm these conclusions and evaluate other commercial programs. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction: a systematic review and meta-analysis of randomized controlled trials

PubMed Central

Ha, Vanessa; Sievenpiper, John L.; de Souza, Russell J.; Jayalath, Viranda H.; Mirrahimi, Arash; Agarwal, Arnav; Chiavaroli, Laura; Mejia, Sonia Blanco; Sacks, Frank M.; Di Buono, Marco; Bernstein, Adam M.; Leiter, Lawrence A.; Kris-Etherton, Penny M.; Vuksan, Vladimir; Bazinet, Richard P.; Josse, Robert G.; Beyene, Joseph; Kendall, Cyril W.C.; Jenkins, David J.A.

2014-01-01

Background: Evidence from controlled trials encourages the intake of dietary pulses (beans, chickpeas, lentils and peas) as a method of improving dyslipidemia, but heart health guidelines have stopped short of ascribing specific benefits to this type of intervention or have graded the beneficial evidence as low. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction. Methods: We searched electronic databases and bibliographies of selected trials for relevant articles published through Feb. 5, 2014. We included RCTs of at least 3 weeks’ duration that compared a diet emphasizing dietary pulse intake with an isocaloric diet that did not include dietary pulses. The lipid targets investigated were low-density lipoprotein (LDL) cholesterol, apolipoprotein B and non–high-density lipoprotein (non-HDL) cholesterol. We pooled data using a random-effects model. Results: We identified 26 RCTs (n = 1037) that satisfied the inclusion criteria. Diets emphasizing dietary pulse intake at a median dose of 130 g/d (about 1 serving daily) significantly lowered LDL cholesterol levels compared with the control diets (mean difference −0.17 mmol/L, 95% confidence interval −0.25 to −0.09 mmol/L). Treatment effects on apolipoprotein B and non-HDL cholesterol were not observed. Interpretation: Our findings suggest that dietary pulse intake significantly reduces LDL cholesterol levels. Trials of longer duration and higher quality are needed to verify these results. Trial registration: ClinicalTrials.gov, no. NCT01594567. PMID:24710915

The short-term efficacy of vena cava filters for the prevention of pulmonary embolism in patients with venous thromboembolism receiving anticoagulation: Meta-analysis of randomized controlled trials.

PubMed

Jiang, Jun; Jiao, Yuanyong; Zhang, Xiwei

2017-10-01

Objectives To perform a meta-analysis of randomized controlled trials assessing the effectiveness of inferior vena cava filters in patients with deep vein thrombosis for preventing pulmonary embolism. Method Relevant randomized controlled trials of inferior vena cava filters for the prevention of pulmonary embolism were identified by searching electronic databases updated in February 2016. Relative risks of recurrent pulmonary embolism, recurrent deep vein thrombosis, and mortality at three months were analyzed. Results Three published randomized controlled trials were included involving a total of 863 deep vein thrombosis patients. No significant differences were detected with inferior vena cava filters placement with regard to the incidence of recurrent pulmonary embolism or fatal pulmonary embolism. There were also no significant differences in the incidence of recurrent deep vein thrombosis or mortality with inferior vena cava filters placement at three months. Conclusions Inferior vena cava filter in addition to anticoagulation was not associated with a reduction in the incidence of recurrent pulmonary embolism as compared with anticoagulation alone in patients with deep vein thrombosis in the short term.

Does peer-assisted learning improve academic performance? A scoping review.

PubMed

Williams, Brett; Reddy, Priya

2016-07-01

Due to the diverse and ever-changing nature of the healthcare industry, teaching pedagogies such as peer-assisted learning (PAL) are being implemented to align with external competency standards. A scoping review was conducted in order to map the breadth of literature available on PAL and its impact on student performance. This review used Arksey and O'Malley's six stage scoping methodology. The databases searched included: Cinahl, Ovid Medline, Proquest and Embase as well as grey literature sites and dissertations. 22 articles were included in this review, 10 of which were mixed methods randomised controlled trials, one retrospective study, four controlled trials, two randomised cross over controlled trial, three prospective randomised controlled trials, one thesis and one comparative research design. Analysis of the included articles identified three major themes outlining student performance. Student teachers themselves showed the most significant improvement in objective outcomes. The predominant healthcare field addressed were medical students with very few studies being completed on other professions. The search indicated an overall positive response to PAL with the measurable outcome of student tutors being of most significance. Further research is required to determine the relevance for the wider healthcare community. Copyright © 2016 Elsevier Ltd. All rights reserved.

Meta-analysis: the efficacy of rectal beclomethasone dipropionate vs. 5-aminosalicylic acid in mild to moderate distal ulcerative colitis.

PubMed

Manguso, F; Balzano, A

2007-07-01

Beclomethasone dipropionate (BDP) is a second-generation steroid with topical effects and minimal systemic activity for patients with ulcerative colitis (UC). To review all available literature to assess the efficacy of enema/foam BDP compared with enema/foam 5-aminosalicylic acid (5-ASA) in the control of left-sided mild-moderate UC. We selected randomized controlled trials of enema/foam BDP compared with enema/foam 5-ASA treatment in patients with UC. Two reviewers assessed trial quality and extracted data independently. Four trials involving 428 UC patients, 209 treated with 5-ASA (1-4 g o.d.) and 219 with BDP (3 mg o.d.), were included. Intention-to-treat analysis showed that 5-ASA induced improvement/remission of UC in 146 (69.9%) patients, while BDP in 143 (65.3%). The test for heterogeneity (Cochran Q) was not significant and Mantel-Haenszel pooled estimate of odds ratio was 1.23 (95% CI = 0.82-1.85). The results did not change when analysis was performed on a per-protocol basis. The randomized controlled trials identified in this review showed that rectal BDP has equal effect as 5-ASA to control symptoms in UC.

Implantable cardioverter defibrillators for primary prevention in patients with nonischemic cardiomyopathy: A systematic review and meta-analysis.

PubMed

Akel, Tamer; Lafferty, James

2017-06-01

Implantable cardioverter defibrillators (ICDs) have proved their favorable outcomes on survival in selected patients with cardiomyopathy. Although previous meta-analyses have shown benefit for their use in primary prevention, the evidence remains less robust for patients with nonischemic cardiomyopathy (NICM) in comparison to patients with coronary artery disease (CAD). To evaluate the effect of ICD therapy on reducing all-cause mortality and sudden cardiac death (SCD) in patients with NICM. PubMed (1993-2016), the Cochrane Central Register of Controlled Trials (2000-2016), reference lists of relevant articles, and previous meta-analyses. Search terms included defibrillator, heart failure, cardiomyopathy, randomized controlled trials, and clinical trials. Eligible trials were randomized controlled trials with at least an arm of ICD, an arm of medical therapy and enrolled some patients with NICM. The primary endpoint in the trials should include all-cause mortality or mortality from SCD. Hazard ratios (HRs) for all-cause mortality and mortality from SCD were either extracted or calculated along with their standard errors. Of the 1047 abstracts retained by the initial screen, eight randomized controlled trials were identified. Five of these trials reported relevant data regarding patients with NICM and were subsequently included in this meta-analysis. Pooled analysis of HRs suggested a statistically significant reduction in all-cause mortality among a total of 2573 patients randomized to ICD vs medical therapy (HR 0.80; 95% CI, 0.67-0.96; P=.02). Pooled analysis of HRs for mortality from SCD was also statistically significant (n=1677) (HR 0.51; 95% CI, 0.34-0.76; P=.001). ICD implantation is beneficial in terms of all-cause mortality and mortality from SCD in certain subgroups of patients with NICM. © 2017 John Wiley & Sons Ltd.

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

Switching in Feedforward Control of Grip Force During Tool-Mediated Interaction With Elastic Force Fields

PubMed Central

White, Olivier; Karniel, Amir; Papaxanthis, Charalambos; Barbiero, Marie; Nisky, Ilana

2018-01-01

Switched systems are common in artificial control systems. Here, we suggest that the brain adopts a switched feedforward control of grip forces during manipulation of objects. We measured how participants modulated grip force when interacting with soft and rigid virtual objects when stiffness varied continuously between trials. We identified a sudden phase transition between two forms of feedforward control that differed in the timing of the synchronization between the anticipated load force and the applied grip force. The switch occurred several trials after a threshold stiffness level in the range 100–200 N/m. These results suggest that in the control of grip force, the brain acts as a switching control system. This opens new research questions as to the nature of the discrete state variables that drive the switching. PMID:29930504

The use of the exit interview to reduce turnover amongst healthcare professionals.

PubMed

Flint, Anndrea; Webster, Joan

2011-01-19

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 used a comprehensive search strategy including an electronic search of the following databases: DARE, CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC (search date: 7 September 2010) and EPOC Specialised Register (search date: 30 September 2009). We also screened the reference lists of included studies and relevant reviews. Randomised controlled trials, controlled clinical trials, controlled before and 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 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. 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.

Azelaic acid in the treatment of papulopustular rosacea: a systematic review of randomized controlled trials.

PubMed

Liu, Rosemarie H; Smith, Molly K; Basta, Sameh A; Farmer, Evan R

2006-08-01

To evaluate the clinical efficacy of topical 20% azelaic acid cream and 15% azelaic acid gel compared with their respective vehicles and metronidazole gel in the treatment of papulopustular rosacea. Electronic searches of MEDLINE, EMBASE, BIOSIS, and SciSearch through July or August 2004 and the Cochrane Central Register of Controlled Trials through 2004 (issue 3). We performed hand searches of reference lists, conference proceedings, and clinical trial databases. Experts in rosacea and azelaic acid were contacted. Randomized controlled trials involving topical azelaic acid (cream or gel) for the treatment of rosacea compared with placebo or other topical treatments. Two authors independently examined the studies identified by the searches. Ten studies were identified, of which 5 were included (873 patients). Two authors independently extracted data from the included studies, then jointly assessed methodological quality using a quality assessment scale. Because standard deviation data were not available for 4 of the 5 studies, a meta-analysis could not be conducted. Four of the 5 studies demonstrated significant decreases in mean inflammatory lesion count and erythema severity after treatment with azelaic acid compared with vehicle. None of the studies showed any significant decrease in telangiectasia severity. Azelaic acid in 20% cream and 15% gel formulations appears to be effective in the treatment of papulopustular rosacea, particularly in regard to decreases in mean inflammatory lesion count and erythema severity. Compared with metronidazole, azelaic acid appears to be an equally effective, if not better, treatment option.

Reporting Quality of Social and Psychological Intervention Trials: A Systematic Review of Reporting Guidelines and Trial Publications

PubMed Central

Grant, Sean P.; Mayo-Wilson, Evan; Melendez-Torres, G. J.; Montgomery, Paul

2013-01-01

Background Previous reviews show that reporting guidelines have improved the quality of trial reports in medicine, yet existing guidelines may not be fully suited for social and psychological intervention trials. Objective/Design We conducted a two-part study that reviewed (1) reporting guidelines for and (2) the reporting quality of social and psychological intervention trials. Data Sources (1) To identify reporting guidelines, we systematically searched multiple electronic databases and reporting guideline registries. (2) To identify trials, we hand-searched 40 journals with the 10 highest impact factors in clinical psychology, criminology, education, and social work. Eligibility (1) Reporting guidelines consisted of articles introducing a checklist of reporting standards relevant to social and psychological intervention trials. (2) Trials reported randomised experiments of complex interventions with psychological, social, or health outcomes. Results (1) We identified 19 reporting guidelines that yielded 147 reporting standards relevant to social and psychological interventions. Social and behavioural science guidelines included 89 standards not found in CONSORT guidelines. However, CONSORT guidelines used more recommended techniques for development and dissemination compared to other guidelines. (2) Our review of trials (n = 239) revealed that many standards were poorly reported, such as identification as a randomised trial in titles (20% reported the information) and abstracts (55%); information about blinding (15%), sequence generation (23%), and allocation concealment (17%); and details about actual delivery of experimental (43%) and control interventions (34%), participant uptake (25%), and service environment (28%). Only 11 of 40 journals referenced reporting guidelines in “Instructions to Authors.” Conclusion Existing reporting guidelines have important limitations in content, development, and/or dissemination. Important details are routinely missing from trial publications; most leading journals in social and behavioural sciences do not ask authors to follow reporting standards. Findings demonstrate a need to develop a CONSORT extension with updated standards for social and psychological intervention trials. PMID:23734256

Methods to improve patient recruitment and retention in stroke trials.

PubMed

Berge, Eivind; Stapf, Christian; Al-Shahi Salman, Rustam; Ford, Gary A; Sandercock, Peter; van der Worp, H Bart; Petersson, Jesper; Dippel, Diederik Wj; Krieger, Derk W; Lees, Kennedy R

2016-08-01

The success of randomized-controlled stroke trials is dependent on the recruitment and retention of a sufficient number of patients, but fewer than half of all trials meet their target number of patients. We performed a search and review of the literature, and conducted a survey and workshop among 56 European stroke trialists, to identify barriers, suggest methods to improve recruitment and retention, and make a priority list of interventions that merit further evaluation. The survey and workshop identified a number of barriers to patient recruitment and retention, from patients' incapacity to consent, to handicaps that prevent patients from participation in trial-specific follow-up. Methods to improve recruitment and retention may include simple interventions with individual participants, funding of research networks, and reimbursement of new treatments by health services only when delivered within clinical trials. The literature review revealed that few methods have been formally evaluated. The top five priorities for evaluation identified in the workshop were as follows: short and illustrated patient information leaflets, nonwritten consent, reimbursement for new interventions only within a study, and monetary incentives to institutions taking part in research (for recruitment); and involvement of patient groups, remote and central follow-up, use of mobile devices, and reminders to patients about their consent to participate (for retention). Many interventions have been used with the aim of improving recruitment and retention of patients in stroke studies, but only a minority has been evaluated. We have identified methods that could be tested, and propose that such evaluations may be nested within on-going clinical trials. © 2016 World Stroke Organization.

Moderators of remission with interpersonal counselling or drug treatment in primary care patients with depression: randomised controlled trial.

PubMed

Menchetti, Marco; Rucci, Paola; Bortolotti, Biancamaria; Bombi, Annarosa; Scocco, Paolo; Kraemer, Helena Chmura; Berardi, Domenico

2014-02-01

Despite depressive disorders being very common there has been little research to guide primary care physicians on the choice of treatment for patients with mild to moderate depression. To evaluate the efficacy of interpersonal counselling compared with selective serotonin reuptake inhibitors (SSRIs), in primary care attenders with major depression and to identify moderators of treatment outcome. A randomised controlled trial in nine centres (DEPICS, Australian New Zealand Clinical Trials Registry number: ACTRN12608000479303). The primary outcome was remission of the depressive episode (defined as a Hamilton Rating Scale for Depression score ≤7 at 2 months). Daily functioning was assessed using the Work and Social Adjustment Scale. Logistic regression models were used to identify moderators of treatment outcome. The percentage of patients who achieved remission at 2 months was significantly higher in the interpersonal counselling group compared with the SSRI group (58.7% v. 45.1%, P = 0.021). Five moderators of treatment outcome were found: depression severity, functional impairment, anxiety comorbidity, previous depressive episodes and smoking habit. We identified some patient characteristics predicting a differential outcome with pharmacological and psychological interventions. Should our results be confirmed in future studies, these characteristics will help clinicians to define criteria for first-line treatment of depression targeted to patients' characteristics.

Statistical monitoring of data quality and consistency in the Stomach Cancer Adjuvant Multi-institutional Trial Group Trial.

PubMed

Timmermans, Catherine; Doffagne, Erik; Venet, David; Desmet, Lieven; Legrand, Catherine; Burzykowski, Tomasz; Buyse, Marc

2016-01-01

Data quality may impact the outcome of clinical trials; hence, there is a need to implement quality control strategies for the data collected. Traditional approaches to quality control have primarily used source data verification during on-site monitoring visits, but these approaches are hugely expensive as well as ineffective. There is growing interest in central statistical monitoring (CSM) as an effective way to ensure data quality and consistency in multicenter clinical trials. CSM with SMART™ uses advanced statistical tools that help identify centers with atypical data patterns which might be the sign of an underlying quality issue. This approach was used to assess the quality and consistency of the data collected in the Stomach Cancer Adjuvant Multi-institutional Trial Group Trial, involving 1495 patients across 232 centers in Japan. In the Stomach Cancer Adjuvant Multi-institutional Trial Group Trial, very few atypical data patterns were found among the participating centers, and none of these patterns were deemed to be related to a quality issue that could significantly affect the outcome of the trial. CSM can be used to provide a check of the quality of the data from completed multicenter clinical trials before analysis, publication, and submission of the results to regulatory agencies. It can also form the basis of a risk-based monitoring strategy in ongoing multicenter trials. CSM aims at improving data quality in clinical trials while also reducing monitoring costs.

Genetic control and comparative genomic analysis of flowering time in Setaria (Poaceae).

PubMed

Mauro-Herrera, Margarita; Wang, Xuewen; Barbier, Hugues; Brutnell, Thomas P; Devos, Katrien M; Doust, Andrew N

2013-02-01

We report the first study on the genetic control of flowering in Setaria, a panicoid grass closely related to switchgrass, and in the same subfamily as maize and sorghum. A recombinant inbred line mapping population derived from a cross between domesticated Setaria italica (foxtail millet) and its wild relative Setaria viridis (green millet), was grown in eight trials with varying environmental conditions to identify a small number of quantitative trait loci (QTL) that control differences in flowering time. Many of the QTL across trials colocalize, suggesting that the genetic control of flowering in Setaria is robust across a range of photoperiod and other environmental factors. A detailed comparison of QTL for flowering in Setaria, sorghum, and maize indicates that several of the major QTL regions identified in maize and sorghum are syntenic orthologs with Setaria QTL, although the maize large effect QTL on chromosome 10 is not. Several Setaria QTL intervals had multiple LOD peaks and were composed of multiple syntenic blocks, suggesting that observed QTL represent multiple tightly linked loci. Candidate genes from flowering time pathways identified in rice and Arabidopsis were identified in Setaria QTL intervals, including those involved in the CONSTANS photoperiod pathway. However, only three of the approximately seven genes cloned for flowering time in maize colocalized with Setaria QTL. This suggests that variation in flowering time in separate grass lineages is controlled by a combination of conserved and lineage specific genes.

Genetic Control and Comparative Genomic Analysis of Flowering Time in Setaria (Poaceae)

PubMed Central

Mauro-Herrera, Margarita; Wang, Xuewen; Barbier, Hugues; Brutnell, Thomas P.; Devos, Katrien M.; Doust, Andrew N.

2013-01-01

We report the first study on the genetic control of flowering in Setaria, a panicoid grass closely related to switchgrass, and in the same subfamily as maize and sorghum. A recombinant inbred line mapping population derived from a cross between domesticated Setaria italica (foxtail millet) and its wild relative Setaria viridis (green millet), was grown in eight trials with varying environmental conditions to identify a small number of quantitative trait loci (QTL) that control differences in flowering time. Many of the QTL across trials colocalize, suggesting that the genetic control of flowering in Setaria is robust across a range of photoperiod and other environmental factors. A detailed comparison of QTL for flowering in Setaria, sorghum, and maize indicates that several of the major QTL regions identified in maize and sorghum are syntenic orthologs with Setaria QTL, although the maize large effect QTL on chromosome 10 is not. Several Setaria QTL intervals had multiple LOD peaks and were composed of multiple syntenic blocks, suggesting that observed QTL represent multiple tightly linked loci. Candidate genes from flowering time pathways identified in rice and Arabidopsis were identified in Setaria QTL intervals, including those involved in the CONSTANS photoperiod pathway. However, only three of the approximately seven genes cloned for flowering time in maize colocalized with Setaria QTL. This suggests that variation in flowering time in separate grass lineages is controlled by a combination of conserved and lineage specific genes. PMID:23390604

The National Drug Abuse Treatment Clinical Trials Network Data Share Project: Website Design, Usage, Challenges and Future Directions

PubMed Central

Shmueli-Blumberg, Dikla; Hu, Lian; Allen, Colleen; Frasketi, Michael; Wu, Li-Tzy; VanVeldhuisen, Paul

2014-01-01

Background The are many benefits of data sharing, including the promotion of new research from effective use of existing data, replication of findings through re-analysis of pooled data files, meta-analysis using individual patient data, and reinforcement of open scientific inquiry. A randomized controlled trial is considered as the “gold standard” for establishing treatment effectiveness, but clinical trial research is very costly and sharing data is an opportunity to expand the investment of the clinical trial beyond its original goals at minimal costs. Purpose We describe the goals, developments, and usage of the Data Share website (www.ctndatashare.org) for the National Drug Abuse Treatment Clinical Trials Network (CTN) in the US, including lessons learned, limitations and major revisions and considerations for future directions to improve data sharing. Methods Data management and programming procedures were conducted to produce uniform and Health Insurance Portability and Accountability Act (HIPAA)-compliant de-identified research data files from the completed trials of the CTN for archiving, managing, and sharing on the Data Share website. Results Since its inception in 2006 and through October 2012, nearly 1700 downloads from 27 clinical trials have been accessed from the Data Share website, with the use increasing over the years. Individuals from 31 countries have downloaded data from the website, and there have been at least 13 publications derived from analyzing data through the public Data Share website. Limitations Minimal control over data requests and usage has resulted in little information and lack of control regarding how the data from the website are used. Lack of uniformity in data elements collected across CTN trials has limited cross-study analyses. Conclusions The Data Share website offers researchers easy access to deidentified data files with the goal to promote additional research and identify new findings from completed CTN studies. To maximize the utility of the website, on-going collaborative efforts are needed to standardize the core measures used for data collection in the CTN studies with the goal to increase their comparability and to facilitate the ability to pool data files for cross-study analyses. PMID:24085772

Chemoprophylaxis in Contacts of Patients with Cholera: Systematic Review and Meta-Analysis

PubMed Central

Reveiz, Ludovic; Chapman, Evelina; Ramon-Pardo, Pilar; Koehlmoos, Tracey Perez; Cuervo, Luis Gabriel; Aldighieri, Sylvain; Chambliss, Amy

2011-01-01

Introduction There is a pressing need for effective measures to prevent the spread of cholera. Our systematic review assesses the effects of chemoprophylaxis in preventing cholera among exposed contacts. Methods and Findings We considered published and unpublished reports of studies up to July 2011. For this we searched: PubMed (1966 to July, 2011), Embase (1980 to July 2011), Cochrane Central Register of Controlled Trials (6; 2011), LILACS (1982 to July, 2011), the International Clinical Trials Registry Platform (July 2011) and references of identified publications. We included controlled clinical trials (randomized and non-randomized) in which chemoprophylaxis was used to prevent cholera among patient contacts. The main outcome measures were hospitalization and laboratory diagnosis of cholera in contacts for cholera patients. We assessed the risk of bias. We identified 2638 references and these included 2 randomized trials and 5 controlled trials that added up to a total of 4,154 participants. The risk of bias scored high for most trials. The combined results from two trials found that chemoprophylaxis reduced hospitalization of contacts during the follow-up period by 8–12 days (2826 participants; RR 0.54 95% CI 0.40–0.74;I2 0%). A meta-analysis of five trials found a significant reduction in disease among contacts with at least one positive sample who received chemoprophylaxis during the overall follow-up (range 4–15 days) (1,414 participants; RR 0.35 95% CI 0.18–0.66;I2 74%). A significant reduction in the number of positive samples was also found with chemoprophylaxis (3 CCT; 6,918 samples; RR 0.39 95% CI 0.29–0.51;I2 0%). Conclusion Our findings suggest that chemoprophylaxis has a protective effect among household contacts of people with cholera but the results are based on studies with a high risk of bias. Hence, there is a need for adequate reliable research that allows balancing benefits and harms by evaluating the effects of chemoprophylaxis. PMID:22102873

Influence of control group on effect size in trials of acupuncture for chronic pain: a secondary analysis of an individual patient data meta-analysis.

PubMed

MacPherson, Hugh; Vertosick, Emily; Lewith, George; Linde, Klaus; Sherman, Karen J; Witt, Claudia M; Vickers, Andrew J

2014-01-01

In a recent individual patient data meta-analysis, acupuncture was found to be superior to both sham and non-sham controls in patients with chronic pain. In this paper we identify variations in types of sham and non-sham controls used and analyze their impact on the effect size of acupuncture. Based on literature searches of acupuncture trials involving patients with headache and migraine, osteoarthritis, and back, neck and shoulder pain, 29 trials met inclusion criteria, 20 involving sham controls (n = 5,230) and 18 non-sham controls (n = 14,597). For sham controls, we analysed non-needle sham, penetrating sham needles and non-penetrating sham needles. For non-sham controls, we analysed non-specified routine care and protocol-guided care. Using meta-regression we explored impact of choice of control on effect of acupuncture. Acupuncture was significantly superior to all categories of control group. For trials that used penetrating needles for sham control, acupuncture had smaller effect sizes than for trials with non-penetrating sham or sham control without needles. The difference in effect size was -0.45 (95% C.I. -0.78, -0.12; p = 0.007), or -0.19 (95% C.I. -0.39, 0.01; p = 0.058) after exclusion of outlying studies showing very large effects of acupuncture. In trials with non-sham controls, larger effect sizes associated with acupuncture vs. non-specified routine care than vs. protocol-guided care. Although the difference in effect size was large (0.26), it was not significant with a wide confidence interval (95% C.I. -0.05, 0.57, p = 0.1). Acupuncture is significantly superior to control irrespective of the subtype of control. While the choice of control should be driven by the study question, our findings can help inform study design in acupuncture, particularly with respect to sample size. Penetrating needles appear to have important physiologic activity. We recommend that this type of sham be avoided.

INVESTIGATE-I (INVasive Evaluation before Surgical Treatment of Incontinence Gives Added Therapeutic Effect?): a mixed-methods study to assess the feasibility of a future randomised controlled trial of invasive urodynamic testing prior to surgery for stress urinary incontinence in women.

PubMed

Hilton, Paul; Armstrong, Natalie; Brennand, Catherine; Howel, Denise; Shen, Jing; Bryant, Andrew; Tincello, Douglas G; Lucas, Malcolm G; Buckley, Brian S; Chapple, Christopher R; Homer, Tara; Vale, Luke; McColl, Elaine

2015-02-01

The position of invasive urodynamic testing in the diagnostic pathway for urinary incontinence (UI) is unclear. Systematic reviews have called for further trials evaluating clinical utility, although a preliminary feasibility study was considered appropriate. To inform the decision whether or not to proceed to a definitive randomised trial of invasive urodynamic testing compared with clinical assessment with non-invasive tests, prior to surgery in women with stress UI (SUI) or stress predominant mixed UI (MUI). A mixed-methods study comprising a pragmatic multicentre randomised pilot trial; economic evaluation; survey of clinicians' views about invasive urodynamic testing; qualitative interviews with clinicians and trial participants. Urogynaecology, female urology and general gynaecology units in Newcastle, Leicester, Swansea, Sheffield, Northumberland, Gateshead and South Tees. Trial recruits were women with SUI or stress predominant MUI who were considering surgery after unsuccessful conservative treatment. Relevant clinicians completed two online surveys. Subsets of survey respondents and trial participants took part in separate qualitative interview studies. Pilot trial participants were randomised to undergo clinical assessment with non-invasive tests (control arm); or assessment as controls, plus invasive urodynamic testing (intervention arm). Confirmation that units can identify and recruit eligible women; acceptability of investigation strategies and data collection tools; acquisition of outcome data to determine the sample size for a definitive trial. The proposed primary outcome for the definitive trial was International Consultation on Incontinence Modular Questionnaire (ICIQ) Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) (total score) 6 months after surgery or the start of non-surgical treatment; secondary outcomes included: ICIQ-FLUTS (subscales); ICIQ Urinary Incontinence Short Form; ICIQ Lower Urinary Tract Symptoms Quality of Life; Urogenital Distress Inventory; EuroQol-5D; costs, quality-adjusted life-years (QALYs) and incremental cost per QALY, Short Form 12; 3-day bladder diary. Of 284 eligible women, 222 (78%) were recruited; 165/219 (75%) returned questionnaires at baseline and 125/200 (63%) who were sent questionnaires at follow-up. There were few missing data items in returned questionnaires, with individual outcome scales calculable for 81%-94%. Most women underwent surgery; management plans were changed in 19 (19%) participants following invasive urodynamic testing. Participant Costs Questionnaires were returned by 53% 6 months after treatment; complete data to undertake cost-utility analysis were available in 27% (intervention) and 47% (control). While insufficient to recommend changes in practice, the results suggest further research would be valuable. All clinicians responding to the survey had access to invasive urodynamic testing, and most saw it as essential prior to surgery in women with SUI with or without other symptoms; nevertheless, 70% considered the research question underlying INVESTIGATE important and most were willing to randomise patients in a definitive trial. Participants interviewed were positive about the trial and associated documentation; the desire of some women to avoid invasive urodynamic testing contrasted with opinions expressed by clinicians through both survey and interview responses. All elements of a definitive trial and economic evaluation were rehearsed; several areas for protocol modification were identified. Such a trial would require to 400-900 participants, depending on the difference in primary outcome sought. A definitive trial of invasive urodynamic testing versus clinical assessment prior to surgery for SUI or stress predominant MUI should be undertaken. Current Controlled Trials ISRCTN71327395. The National Institute for Health Research Health Technology Assessment programme.

A methodological approach for assessing the uptake of core outcome sets using ClinicalTrials.gov: findings from a review of randomised controlled trials of rheumatoid arthritis.

PubMed

Kirkham, Jamie J; Clarke, Mike; Williamson, Paula R

2017-05-17

Objective  To assess the uptake of the rheumatoid arthritis core outcome set using a new assessment method of calculating uptake from data in clinical trial registry entries. Design  Review of randomised trials. Setting  ClinicalTrials.gov. Subjects  273 randomised trials of drug interventions for the treatment of rheumatoid arthritis and registered in ClinicalTrials.gov between 2002 and 2016. Full publications were identified for completed studies from information in the trial registry or from an internet search using Google and the citation database Web of Science. Main outcome measure  The percentage of trials reporting or planning to measure the rheumatoid arthritis core outcome set calculated from the information presented in the trial registry and compared with the percentage reporting the rheumatoid arthritis core outcome set in the resulting trial publications. Results  The full rheumatoid arthritis core outcome set was reported in 81% (116/143) of trials identified on the registry as completed (or terminated) for which results were found in either the published literature or the registry. For trials identified on the registry as completed (or terminated), using information only available in the registry gives an estimate for uptake of 77% (145/189). Conclusions  The uptake of the rheumatoid arthritis core outcome set in clinical trials has continued to increase over time. Using the information on outcomes listed for completed or terminated studies in a trial registry provides a reasonable estimate of the uptake of a core outcome set and is a more efficient and up-to-date approach than examining the outcomes in published trial reports. The method proposed may provide an efficient approach for an up-to-date assessment of the uptake of the 300 core outcome sets already published. 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.

Prevention of emergency physician migratory contamination in a cluster randomized trial to increase tissue plasminogen activator use in stroke (the INSTINCT trial).

PubMed

Weston, Victoria C; Meurer, William J; Frederiksen, Shirley M; Fox, Allison K; Scott, Phillip A

2014-12-01

Cluster randomized trials (CRTs) are increasingly used to evaluate quality improvement interventions aimed at health care providers. In trials testing emergency department (ED) interventions, migration of emergency physicians (EPs) between hospitals is an important concern, as contamination may affect both internal and external validity. We hypothesized that geographically isolating EDs would prevent migratory contamination in a CRT designed to increase ED delivery of tissue plasminogen activator (tPA) in stroke (the INSTINCT trial). INSTINCT was a prospective, cluster randomized, controlled trial. Twenty-four Michigan community hospitals were randomly selected in matched pairs for study. Contamination was defined at the cluster level, with substantial contamination defined a priori as greater than 10% of EPs affected. Nonadherence, total crossover (contamination+nonadherence), migration distance, and characteristics were determined. Three hundred seven EPs were identified at all sites. Overall, 7 (2.3%) changed study sites. One moved between control sites, leaving 6 (2.0%) total crossovers. Of these, 2 (0.7%) moved from intervention to control (contamination); and 4 (1.3%) moved from control to intervention (nonadherence). Contamination was observed in 2 of 12 control sites, with 17% and 9% contamination of the total site EP workforce at follow-up, respectively. Average migration distance was 42 miles for all EPs moving in the study and 35 miles for EPs moving from intervention to control sites. The mobile nature of EPs should be considered in the design of quality improvement CRTs. Increased reporting of contamination in CRTs is encouraged to clarify thresholds and facilitate CRT design. Copyright © 2014 Elsevier Inc. All rights reserved.

Control charts for monitoring accumulating adverse event count frequencies from single and multiple blinded trials.

PubMed

Gould, A Lawrence

2016-12-30

Conventional practice monitors accumulating information about drug safety in terms of the numbers of adverse events reported from trials in a drug development program. Estimates of between-treatment adverse event risk differences can be obtained readily from unblinded trials with adjustment for differences among trials using conventional statistical methods. Recent regulatory guidelines require monitoring the cumulative frequency of adverse event reports to identify possible between-treatment adverse event risk differences without unblinding ongoing trials. Conventional statistical methods for assessing between-treatment adverse event risks cannot be applied when the trials are blinded. However, CUSUM charts can be used to monitor the accumulation of adverse event occurrences. CUSUM charts for monitoring adverse event occurrence in a Bayesian paradigm are based on assumptions about the process generating the adverse event counts in a trial as expressed by informative prior distributions. This article describes the construction of control charts for monitoring adverse event occurrence based on statistical models for the processes, characterizes their statistical properties, and describes how to construct useful prior distributions. Application of the approach to two adverse events of interest in a real trial gave nearly identical results for binomial and Poisson observed event count likelihoods. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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.

Trimetazidine: a meta-analysis of randomised controlled trials in heart failure.

PubMed

Gao, Dengfeng; Ning, Ning; Niu, Xiaolin; Hao, Guanghua; Meng, Zhe

2011-02-01

To explore whether trimetazidine could improve symptoms, cardiac functions and clinical outcomes in patients with heart failure (HF). A systematic literature search was conducted to identify randomised controlled trials (RCT) of trimetazidine for HF between 1966 and May 2010 in Pubmed, the Cochrane Central Registry of Clinical Trials and EMBASE. Reports of trials were sought that compared trimetazidine with placebo control for chronic HF in adults, with outcomes including all-cause mortality, hospitalisation, cardiovascular events, changes in cardiac function parameters and exercise capacity. 17 trials with data for 955 patients were identified by the literature search. Trimetazidine therapy was associated with a significant improvement in left ventricular ejection fraction in patients with both ischaemic (weighted mean difference (WMD) with placebo 7.37%; 95% CI 6.05 to 8.70; p<0.01) and non-ischaemic HF (WMD 8.72%; 95% CI 5.51 to 11.92; p<0.01). With trimetazidine therapy, left ventricular end-systolic volume was significantly reduced (WMD 10.37 ml; 95% CI 15.46 to 5.29; p<0.01) and New York Heart Association classification was improved (WMD 0.41; 95% CI 0.51 to 0.31; p<0.01) as was exercise duration (WMD, 30.26 s; 95% CI 8.77 to 51.75; p<0.01). More importantly, trimetazidine had a significant protective effect for all-cause mortality (RR 0.29; 95% CI 0.17 to 0.49; p<0.00001) and cardiovascular events and hospitalisation (RR 0.42; 95% CI 0.30 to 0.58; p<0.00001). Trimetazidine might be an effective strategy for treating HF. More studies, especially larger multicentre RCT, are warranted to clarify the effect of trimetazidine on HF.

Colorectal adenoma recurrence rates among post-polypectomy patients in the placebo-controlled groups of randomized clinical trials: a meta-analysis

PubMed Central

Shi, Xin; Yang, Zhiping; Wu, Qiong; Fan, Daiming

2017-01-01

Background Evidence regarding the benefit of therapy to prevent the post-polypectomy recurrence of colorectal adenoma is limited. Endoscopic recurrence is the main outcome according to an evaluation of trials involving recurrence prevention. Aim To estimate the recurrence rates of post-polypectomy colorectal adenoma in placebo-controlled arms of randomized clinical trials and to identify the prognostic factors influencing these rates. Methods We combined data from all randomized controlled trials evaluating therapies for colorectal adenoma using placebo from 1988 to 2016. The data were combined in a random-effects model. Primary outcomes were endoscopic adenoma and advanced adenoma recurrence of colorectal adenoma. Results The pooled estimates of the adenoma recurrence rates were 37% (95% confidence interval [CI], 33%-41%; range, 33%-52%) at 1 year, 47% (95% CI, 41%-54%; range, 46%-51%) at 2 years, 41% (95% CI, 33%-48%; range, 20%-61%) at 3 years, 48% (95% CI, 38%-57%; range, 37%-53%) at 4 years, and 60% (95% CI, 52%-68%; range, 48%-68%) at 5 years. The pooled estimates of the advanced adenoma recurrence rates were 10% (95% CI, 6%-15%; range, 7%-13%) at 1 year, 12% (95% CI, 8%-16%; range, 3%-19%) at 3 years, 14% (95% CI, 10%-18%; range, 13%-16%) at 4 years, and 14% (95% CI, 10%-19%; range, 9%-21%) at 5 years. Significant heterogeneity among the randomized clinical trials (P < 0.001) was observed for each recurrence rate. Conclusions This meta-analysis confirms the heterogeneity of recurrence rates among post-polypectomy colorectal adenoma patients who received placebo. No single design variable was identified that might explain the heterogeneity. PMID:28977952

The Effect of Biologic and Targeted Synthetic Drugs on Work- and Productivity-related Outcomes for Patients with Psoriatic Arthritis: A Systematic Review.

PubMed

Iragorri, Nicolas; Hofmeister, Mark; Spackman, Eldon; Hazlewood, Glen S

2018-05-01

To systematically review the effects of biologic therapies for psoriatic arthritis [secukinumab, ustekinumab, adalimumab, etanercept, certolizumab pegol (CZP), apremilast, golimumab (GOL), or infliximab (IFX)] on work productivity. A systematic review of Medline, EMBASE, CENTRAL, and ClinicalTrials.gov was conducted to identify randomized controlled trials reporting on work productivity outcomes at the end of the placebo-controlled double-blind period. There were 7959 records identified. Full text of 377 records was further assessed for eligibility, of which 5 trials were included. All included trials were assessed with the Cochrane Risk of Bias Tool, and 4 out of 5 were judged to be of low risk of bias in most domains. Improvements in self-assessed work productivity were observed in 5 trials (IFX, GOL, CZP, ustekinumab, and apremilast), ranging from a mean difference of -0.9 to -1.8 on a 1-10 scale of self-assessed work productivity (negative change represents improvement), although statistical significance of the results was not reported for CZP and apremilast. Treatment with CZP resulted in a statistically significant reduction in absenteeism (200 mg) and presenteeism (200 and 400 mg). IFX and GOL reported a nonsignificant reduction of absenteeism. The Work Productivity Survey, the Work Limitations Questionnaire, and visual analog scales were used to measure work productivity. Treatment with IFX, GOL, CZP, ustekinumab, and apremilast resulted in improvements in self-reported work productivity. A pooled analysis was not possible because of the clinical heterogeneity of the trials and variability in outcome reporting.

Feeding the brain - The effects of micronutrient interventions on cognitive performance among school-aged children: A systematic review of randomized controlled trials.

PubMed

Lam, Long Fung; Lawlis, Tanya R

2017-08-01

Micronutrients are essential for brain development with deficiencies in specific nutrients linked to impaired cognitive function. Interventions are shown to be beneficial to children's mental development, particularly in subjects who were micronutrient-deficient at baseline but results on healthy subjects remain inconsistent. This systematic review evaluated the effect of micronutrient inventions on different cognitive domains. Studies conducted in both developing and developed countries, and trials that investigate the effect of both single and multiple micronutrient intervention were reviewed. Systematic searches of Medline, CINAHL Plus and Academic Search database were undertaken to identify trials published after year 2000. Randomized controlled trials (RCTs) that evaluate the effect of micronutrients on cognitive performance or academic performance among children aged 4-18 years were included. 19 trials were identified from 18 articles. The major cognitive outcomes assessed included fluid intelligence, crystallized intelligence, short-term memory, long-term memory, cognitive processing speed, attention and concentration, and school performance. Eight of ten trials assessing fluid intelligence reported significant positive effects of micronutrient supplementation among micronutrient-deficient children, especially those who were iron-deficient or iodine-deficient at baseline. The effects of micronutrient interventions on other domains were inconsistent. Improvement in fluid intelligence among micronutrient-deficient children was consistently reported. Further research is needed to provide more definite evidence on the beneficial effects of micronutrient inventions on other cognitive domains and the effects in healthy subjects. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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.

Barriers and Strategies for Recruitment of Racial and Ethnic Minorities: Perspectives from Neurological Clinical Research Coordinators.

PubMed

Haley, Sean J; Southwick, Lauren E; Parikh, Nina S; Rivera, Jazmin; Farrar-Edwards, Dorothy; Boden-Albala, Bernadette

2017-12-01

Randomized controlled trials (RCTs) are the gold standard within evidence-based research. Low participant accrual rates, especially of underrepresented groups (e.g., racial-ethnic minorities), may jeopardize clinical studies' viability and strength of findings. Research has begun to unweave clinical trial mechanics, including the roles of clinical research coordinators, to improve trial participation rates. Two semi-structured focus groups were conducted with a purposive sample of 29 clinical research coordinators (CRCs) at consecutive international stroke conferences in 2013 and 2014 to gain in-depth understanding of coordinator-level barriers to racial-ethnic minority recruitment and retention into neurological trials. Coded transcripts were used to create themes to define concepts, identify associations, summarize findings, and posit explanations. Barriers related to translation, literacy, family composition, and severity of medical diagnosis were identified. Potential strategies included a focus on developing personal relationships with patients, community and patient education, centralized clinical trial administrative systems, and competency focused training and education for CRCs. Patient level barriers to clinical trial recruitment are well documented. Less is known about barriers facing CRCs. Further identification of how and when barriers manifest and the effectiveness of strategies to improve CRCs recruitment efforts is warranted.

Differentiating closed-loop cortical intention from rest: building an asynchronous electrocorticographic BCI.

PubMed

Williams, Jordan J; Rouse, Adam G; Thongpang, Sanitta; Williams, Justin C; Moran, Daniel W

2013-08-01

Recent experiments have shown that electrocorticography (ECoG) can provide robust control signals for a brain-computer interface (BCI). Strategies that attempt to adapt a BCI control algorithm by learning from past trials often assume that the subject is attending to each training trial. Likewise, automatic disabling of movement control would be desirable during resting periods when random brain fluctuations might cause unintended movements of a device. To this end, our goal was to identify ECoG differences that arise between periods of active BCI use and rest. We examined spectral differences in multi-channel, epidural micro-ECoG signals recorded from non-human primates when rest periods were interleaved between blocks of an active BCI control task. Post-hoc analyses demonstrated that these states can be decoded accurately on both a trial-by-trial and real-time basis, and this discriminability remains robust over a period of weeks. In addition, high gamma frequencies showed greater modulation with desired movement direction, while lower frequency components demonstrated greater amplitude differences between task and rest periods, suggesting possible specialized BCI roles for these frequencies. The results presented here provide valuable insight into the neurophysiology of BCI control as well as important considerations toward the design of an asynchronous BCI system.

Differentiating closed-loop cortical intention from rest: building an asynchronous electrocorticographic BCI

NASA Astrophysics Data System (ADS)

Williams, Jordan J.; Rouse, Adam G.; Thongpang, Sanitta; Williams, Justin C.; Moran, Daniel W.

2013-08-01

Objective. Recent experiments have shown that electrocorticography (ECoG) can provide robust control signals for a brain-computer interface (BCI). Strategies that attempt to adapt a BCI control algorithm by learning from past trials often assume that the subject is attending to each training trial. Likewise, automatic disabling of movement control would be desirable during resting periods when random brain fluctuations might cause unintended movements of a device. To this end, our goal was to identify ECoG differences that arise between periods of active BCI use and rest. Approach. We examined spectral differences in multi-channel, epidural micro-ECoG signals recorded from non-human primates when rest periods were interleaved between blocks of an active BCI control task. Main Results. Post-hoc analyses demonstrated that these states can be decoded accurately on both a trial-by-trial and real-time basis, and this discriminability remains robust over a period of weeks. In addition, high gamma frequencies showed greater modulation with desired movement direction, while lower frequency components demonstrated greater amplitude differences between task and rest periods, suggesting possible specialized BCI roles for these frequencies. Significance. The results presented here provide valuable insight into the neurophysiology of BCI control as well as important considerations toward the design of an asynchronous BCI system.

Cognitive control during a spatial Stroop task: Comparing conflict monitoring and prediction of response-outcome theories.

PubMed

Pires, Luís; Leitão, José; Guerrini, Chiara; Simões, Mário R

2017-07-03

Cognitive control allows information processing and behaviour to vary adaptively from moment to moment depending on current goals. Two of the most prominent theories that have been proposed to account for the processing of cognitive control are the Conflict Monitoring Theory (CMT) and the Prediction of Response-Outcome Theory (PRO). According to both theories, the implementation of cognitive control during a trial in a conflict task reflects processing events that occurred in the preceding trial. Both CMT and PRO advocate that the detection of conflict situations leads to the recruitment of cognitive control, but they differ regarding the processing underpinnings of cognitive control during conflict resolution. CMT proposes that conflict between alternative responses is resolved by enhancing the task's relevant dimension, reducing interference from the task's irrelevant dimension(s). This control setup promotes conflict adaptation in the subsequent trial. PRO proposes that conflict is resolved by means of a cost-effectiveness analysis that identifies and suppresses action plans linked to the less appropriate responses, facilitating conflict resolution in the subsequent trial. To adjudicate between these alternatives, we manipulated contingencies pertaining to two-trial sequences (n-1; n), namely, the congruency between task relevant/irrelevant dimensions in trial n-1 and response repetition in trial n. A spatial Stroop task was used, in which task-relevant and irrelevant information were integrated within the same stimulus. In this task, participants were required to attend to the direction of an arrow while ignoring its position. The arrow's direction and position could be congruent (C) or incongruent (IC). In one experiment, trials in which the participant was required to respond according to the position of a circle (PO; position only trials), occupying the sequential position n, were the focus of the analyses. Three experiments were conducted manipulating the trials' sequence structure. In Experiment 1, we studied a low control/low conflict condition (cC trials), and two high control/low conflict conditions (icC with and without response repetition). In Experiment 2, we studied two low control/no conflict conditions (cPO with and without response repetition) and two high control/no conflict conditions (icPO with and without response repetition). In Experiment 3, we studied a high control/high conflict condition (icIC) and two low control/high conflict conditions (cIC with and without response repetition). Overall, our findings are in agreement with previous studies in which both bottom-up processing, linked to response and stimulus position repetition, and top-down processing, linked to cognitive control, were shown to contribute to sequence effects in conflict tasks. Specifically, our observations mainly support PRO's account of conflict resolution, in which the intervention of top-down processing is substantially more complex than in CMT's account. Copyright © 2017 Elsevier B.V. All rights reserved.

Vitex agnus-castus extracts for female reproductive disorders: a systematic review of clinical trials.

PubMed

van Die, M Diana; Burger, Henry G; Teede, Helena J; Bone, Kerry M

2013-05-01

Vitex agnus-castus L. (chaste tree; chasteberry) is a popular herbal treatment, predominantly used for a range of female reproductive conditions in Anglo-American and European practice. The objective of this systematic review was to evaluate the evidence for the efficacy and safety of Vitex extracts from randomised, controlled trials investigating women's health.Eight databases were searched using Latin and common names for Vitex and phytotherapeutic preparations of the herb as a sole agent, together with filters for randomised, controlled trials or clinical trials. Methodological quality was assessed according to the Cochrane risk of bias and Jadad scales, as well as the proposed elaboration of CONSORT for reporting trials on herbal interventions.Thirteen randomised, controlled trials were identified and twelve are included in this review, of which eight investigated premenstrual syndrome, two premenstrual dysphoric disorder, and two latent hyperprolactinaemia. For premenstrual syndrome, seven of eight trials found Vitex extracts to be superior to placebo (5 of 6 studies), pyridoxine (1), and magnesium oxide (1). In premenstrual dysphoric disorder, one study reported Vitex to be equivalent to fluoxetine, while in the other, fluoxetine outperformed Vitex. In latent hyperprolactinaemia, one trial reported it to be superior to placebo for reducing TRH-stimulated prolactin secretion, normalising a shortened luteal phase, increasing mid-luteal progesterone and 17β-oestradiol levels, while the other found Vitex comparable to bromocriptine for reducing serum prolactin levels and ameliorating cyclic mastalgia. Adverse events with Vitex were mild and generally infrequent. The methodological quality of the included studies varied, but was generally moderate-to-high. Limitations include small sample sizes in some studies, heterogeneity of conditions being treated, and a range of reference treatments.Despite some methodological limitations, the results from randomised, controlled trials to date suggest benefits for Vitex extracts in the treatment of premenstrual syndrome, premenstrual dysphoric disorder and latent hyperprolactinaemia. Further research is recommended, and greater transparency in reporting for future trials. Georg Thieme Verlag KG Stuttgart · New York.

Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions.

PubMed

van Galen, Karin P M; Engelen, Eveline T; Mauser-Bunschoten, Evelien P; van Es, Robert J J; Schutgens, Roger E G

2015-12-24

Minor oral surgery or dental extractions (oral or dental procedures) are widely performed and can be complicated by hazardous oral bleeding, especially in people with an inherited bleeding disorder such as haemophilia or Von Willebrand disease. The amount and severity of singular bleedings depend on disease-related factors, such as the severity of the haemophilia, both local and systemic patient factors (such as periodontal inflammation, vasculopathy or platelet dysfunction) and intervention-related factors (such as the type and number of teeth extracted or the dimension of the wound surface). Similar to local haemostatic measures and suturing, antifibrinolytic therapy is a cheap, safe and potentially effective treatment to prevent bleeding complications in individuals with bleeding disorders undergoing oral or dental procedures. However, a systematic review of trials reporting outcomes after oral surgery or a dental procedure in people with an inherited bleeding disorder, with or without, the use of antifibrinolytic agents has not been performed to date. The primary objective was to assess the efficacy of local or systemic use of antifibrinolytic agents to prevent bleeding complications in people with haemophilia or Von Willebrand disease undergoing oral or dental procedures. Secondary objectives were to assess if antifibrinolytic agents can replace or reduce the need for clotting factor concentrate therapy in people with haemophilia or Von Willebrand disease and to further establish the effects of these agents on bleeding in oral or dental procedures for each of these populations. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches of the Cochrane Central Register of Controlled Trials (CENTRAL), of MEDLINE and from handsearching of journals and conference abstract books. We additionally searched the reference lists of relevant articles and reviews. We searched PubMed, Embase and The Cochrane Library. Additional searches were performed in ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP).Date of last search of the Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 14 December 2015. Randomised and quasi-randomised controlled trials in people with haemophilia or Von Willebrand disease undergoing oral or dental procedures using antifibrinolytic agents (tranexamic acid or epsilon aminocaproic acid) to prevent perioperative bleeding compared to no intervention or usual care with or without placebo. Two authors independently screened the titles and abstracts of all identified articles. Full texts were obtained for potentially relevant abstracts and two authors independently assessed these for inclusion based on the selection criteria. A third author verified trial eligibility. Two authors independently performed data extraction and risk of bias assessments using standardized forms. While there were no eligible trials in people with Von Willebrand disease identified, two randomised, double-blind, placebo-controlled trials (total of 59 participants) in people with haemophilia undergoing dental extraction were included. One trial of tranexamic acid published in 1972 included 28 participants with mild, moderate or severe haemophilia A and B and one of epsilon aminocaproic acid published in 1971 included 31 people with haemophilia with factor VIII or factor IX levels less than 15%. Overall, the two included trials showed a beneficial effect of tranexamic acid and EACA, administered systemically, in reducing the number of bleedings, the amount of blood loss and the need for therapeutic clotting factor concentrates. Regarding postoperative bleeding, the tranexamic acid trial showed a risk difference of -0.64 (95% confidence interval -0.93 to - 0.36) and the EACA trial a risk difference of -0.50 (95% confidence interval 0.77 to -0.22). The combined risk difference of both trials was -0.57 (95% confidence interval -0.76 to -0.37), with the quality of the evidence (GRADE) for this outcome is rated as moderate. Side effects occurred once and required stopping epsilon aminocaproic acid (combined risk difference of -0.03 (95% CI -0.08 to 0.13). There was heterogeneity between the two trials regarding the proportion of people with severe haemophilia included, the concomitant standard therapy and fibrinolytic agent treatment regimens used. We cannot exclude that a selection bias has occurred in the epsilon aminocaproic acid trial, but overall the risk of bias appeared to be low for both trials. Despite the discovery of a beneficial effect of systemically administered tranexamic acid and epsilon aminocaproic acid in preventing postoperative bleeding in people with haemophilia undergoing dental extraction, the limited number of randomised controlled trials identified, in combination with the small sample sizes and heterogeneity regarding standard therapy and treatment regimens between the two trials, do not allow us to conclude definite efficacy of antifibrinolytic therapy in oral or dental procedures in people with haemophilia. No trials were identified in people with Von Willebrand disease.

Creatine for women in pregnancy for neuroprotection of the fetus.

PubMed

Dickinson, Hayley; Bain, Emily; Wilkinson, Dominic; Middleton, Philippa; Crowther, Caroline A; Walker, David W

2014-12-19

Creatine is an amino acid derivative and, when phosphorylated (phosphocreatine), is involved in replenishing adenosine triphosphate (ATP) via the creatine kinase reaction. Cells obtain creatine from a diet rich in fish, meat, or dairy and by endogenous synthesis from the amino acids arginine, glycine, and methionine in an approximate 50:50 ratio. Animal studies have shown that creatine may provide fetal neuroprotection when given to the mother through her diet in pregnancy. It is important to assess whether maternally administered creatine in human pregnancy (at times of known, suspected, or potential fetal compromise) may offer neuroprotection to the fetus and may accordingly reduce the risk of adverse neurodevelopmental outcomes, such as cerebral palsy and associated impairments and disabilities arising from fetal brain injury. To assess the effects of creatine when used for neuroprotection of the fetus. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2014). We planned to include all published, unpublished, and ongoing randomised trials and quasi-randomised trials. We planned to include studies reported as abstracts only as well as full-text manuscripts. Trials using a cross-over or cluster-randomised design were not eligible for inclusion.We planned to include trials comparing creatine given to women in pregnancy for fetal neuroprotection (regardless of the route, timing, dose, or duration of administration) with placebo, no treatment, or with an alternative agent aimed at providing fetal neuroprotection. We also planned to include comparisons of different regimens for administration of creatine. We identified no completed or ongoing randomised controlled trials. We found no randomised controlled trials for inclusion in this review. As we did not identify any randomised controlled trials for inclusion in this review, we are unable to comment on implications for practice. Although evidence from animal studies has supported a fetal neuroprotective role for creatine when administered to the mother during pregnancy, no trials assessing creatine in pregnant women for fetal neuroprotection have been published to date. If creatine is established as safe for the mother and her fetus, research efforts should first be directed towards randomised trials comparing creatine with either no intervention (ideally using a placebo), or with alternative agents aimed at providing fetal neuroprotection (including magnesium sulphate for the very preterm infant). If appropriate, these trials should then be followed by studies comparing different creatine regimens (dosage and duration of exposure). Such trials should be high quality and adequately powered to evaluate maternal and infant short and longer-term outcomes (including neurodevelopmental disabilities such as cerebral palsy), and should consider utilisation/costs of health care.

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

Pharmacological interventions for acute pancreatitis.

PubMed

Moggia, Elisabetta; Koti, Rahul; Belgaumkar, Ajay P; Fazio, Federico; Pereira, Stephen P; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2017-04-21

In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure. To assess the effects of different pharmacological interventions in people with acute pancreatitis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). We also searched the references of included trials to identify further trials. We considered only RCTs performed in people with acute pancreatitis, irrespective of aetiology, severity, presence of infection, language, blinding, or publication status for inclusion in the review. Two review authors independently identified trials and extracted data. We did not perform a network meta-analysis as planned because of the lack of information on potential effect modifiers and differences of type of participants included in the different comparisons, when information was available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for the binary outcomes and rate ratios with 95% CIs for count outcomes using a fixed-effect model and random-effects model. We included 84 RCTs with 8234 participants in this review. Six trials (N = 658) did not report any of the outcomes of interest for this review. The remaining 78 trials excluded 210 participants after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin plus ulinastatin, thymosin, ulinastatin, and inactive control. Apart from the comparison of antibiotics versus control, which included a large proportion of participants with necrotising pancreatitis, the remaining comparisons had only a small proportion of patients with this condition. Most trials included either only participants with severe acute pancreatitis or included a mixture of participants with mild acute pancreatitis and severe acute pancreatitis (75 trials). Overall, the risk of bias in trials was unclear or high for all but one of the trials. seven trials were not funded or funded by agencies without vested interest in results. Pharmaceutical companies partially or fully funded 21 trials. The source of funding was not available from the remaining trials.Since we considered short-term mortality as the most important outcome, we presented only these results in detail in the abstract. Sixty-seven studies including 6638 participants reported short-term mortality. There was no evidence of any differences in short-term mortality in any of the comparisons (very low-quality evidence). With regards to other primary outcomes, serious adverse events (number) were lower than control in participants taking lexipafant (rate ratio 0.67, 95% CI 0.46 to 0.96; N = 290; 1 study; very low-quality evidence), octreotide (rate ratio 0.74, 95% CI 0.60 to 0.89; N = 770; 5 studies; very low-quality evidence), somatostatin plus omeprazole (rate ratio 0.36, 95% CI 0.19 to 0.70; N = 140; 1 study; low-quality evidence), and somatostatin plus ulinastatin (rate ratio 0.30, 95% CI 0.15 to 0.60; N = 122; 1 study; low-quality evidence). The proportion of people with organ failure was lower in octreotide than control (OR 0.51, 95% CI 0.27 to 0.97; N = 430; 3 studies; very low-quality evidence). The proportion of people with sepsis was lower in lexipafant than control (OR 0.26, 95% CI 0.08 to 0.83; N = 290; 1 study; very low-quality evidence). There was no evidence of differences in any of the remaining comparisons in these outcomes or for any of the remaining primary outcomes (the proportion of participants experiencing at least one serious adverse event and the occurrence of infected pancreatic necrosis). None of the trials reported heath-related quality of life. Very low-quality evidence suggests that none of the pharmacological treatments studied decrease short-term mortality in people with acute pancreatitis. However, the confidence intervals were wide and consistent with an increase or decrease in short-term mortality due to the interventions. We did not find consistent clinical benefits with any intervention. Because of the limitations in the prognostic scoring systems and because damage to organs may occur in acute pancreatitis before they are clinically manifest, future trials should consider including pancreatitis of all severity but power the study to measure the differences in the subgroup of people with severe acute pancreatitis. It may be difficult to power the studies based on mortality. Future trials in participants with acute pancreatitis should consider other outcomes such as complications or health-related quality of life as primary outcomes. Such trials should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year).

Treatment for avascular necrosis of bone in people with sickle cell disease.

PubMed

Martí-Carvajal, Arturo J; Solà, Ivan; Agreda-Pérez, Luis H

2014-07-10

Avascular necrosis of bone is a frequent and severe complication of sickle cell disease and its treatment is not standardised. To determine the impact of any surgical procedure compared with other surgical interventions or non-surgical procedures, on avascular necrosis of bone in people with sickle cell disease in terms of efficacy and safety. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Additional trials were sought from the reference lists of papers identified by the search strategy.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 17 March 2014. Randomised clinical trials comparing specific therapies for avascular necrosis of bone in people with sickle cell disease. Each author independently extracted data and assessed trial quality. Since only one trial was identified, meta-analysis was not possible. One trial (46 participants) was eligible for inclusion. After randomisation eight participants were withdrawn, mainly because they declined to participate in the trial. Data were analysed for 38 participants at the end of the trial. After a mean follow up of three years, hip core decompression and physical therapy did not show clinical improvement when compared with physical therapy alone using the score from the original trial (an improvement of 18.1 points for those treated with intervention therapy versus an improvement of 15.7 points with control therapy). There was no significant statistical difference between groups regarding major complications (hip pain, relative risk (RR) 0.95 (95% confidence interval (CI) 0.56 to 1.60; vaso-occlusive crises, RR 1.14 (95% CI 0.72 to 1.80; very low quality of evidence); and acute chest syndrome, RR 1.06 (95% CI 0.44 to 2.56; very low quality of evidence)). This trial did not report results on mortality or quality of life. We found no evidence that adding hip core decompression to physical therapy achieves clinical improvement in people with sickle cell disease with avascular necrosis of bone compared to physical therapy alone. However, we highlight that our conclusion is based on one trial with high attrition rates. Further randomised controlled trials are necessary to evaluate the role of hip-core depression for this clinical condition. Endpoints should focus on participants' subjective experience (e.g. quality of life and pain) as well as more objective 'time-to-event' measures (e.g. mortality, survival, hip longevity). The availability of participants to allow adequate trial power will be a key consideration for endpoint choice.

Treatment for avascular necrosis of bone in people with sickle cell disease.

PubMed

Martí-Carvajal, Arturo J; Solà, Ivan; Agreda-Pérez, Luis H

2016-08-09

Avascular necrosis of bone is a frequent and severe complication of sickle cell disease and its treatment is not standardised. This is an update of a previously published Cochrane Review. To determine the impact of any surgical procedure compared with other surgical interventions or non-surgical procedures, on avascular necrosis of bone in people with sickle cell disease in terms of efficacy and safety. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Additional trials were sought from the reference lists of papers identified by the search strategy.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 27 May 2016. Randomized clinical trials comparing specific therapies for avascular necrosis of bone in people with sickle cell disease. Each author independently extracted data and assessed trial quality. Since only one trial was identified, meta-analysis was not possible. One trial (46 participants) was eligible for inclusion. After randomization eight participants were withdrawn, mainly because they declined to participate in the trial. Data were analysed for 38 participants at the end of the trial. After a mean follow up of three years, hip core decompression and physical therapy did not show clinical improvement when compared with physical therapy alone using the score from the original trial (an improvement of 18.1 points for those treated with intervention therapy versus an improvement of 15.7 points with control therapy). There was no significant statistical difference between groups regarding major complications (hip pain, risk ratio 0.95 (95% confidence interval 0.56 to 1.60; vaso-occlusive crises, risk ratio 1.14 (95% confidence interval 0.72 to 1.80; very low quality of evidence); and acute chest syndrome, risk ratio 1.06 (95% confidence interval 0.44 to 2.56; very low quality of evidence)). This trial did not report results on mortality or quality of life. We found no evidence that adding hip core decompression to physical therapy achieves clinical improvement in people with sickle cell disease with avascular necrosis of bone compared to physical therapy alone. However, we highlight that our conclusion is based on one trial with high attrition rates. Further randomized controlled trials are necessary to evaluate the role of hip-core depression for this clinical condition. Endpoints should focus on participants' subjective experience (e.g. quality of life and pain) as well as more objective 'time-to-event' measures (e.g. mortality, survival, hip longevity). The availability of participants to allow adequate trial power will be a key consideration for endpoint choice.

Is There a Role for Oral or Intravenous Ascorbate (Vitamin C) in Treating Patients With Cancer? A Systematic Review

PubMed Central

Hutton, Brian; Ng, Terry; Shorr, Risa; Clemons, Mark

2015-01-01

Background. Many cancer patients receive supplemental ascorbate (vitamin C) in the belief that it synergizes the anticancer effects of chemotherapy and reduces its toxicity. Methods. A systematic review was performed to evaluate the antitumor effects and toxicity of ascorbate treatment. Medline (1946 to March 2014), EMBASE (1947 to March 2014), and the Cochrane central register (1993 to March 2014) were searched for randomized and observational studies. Results. Of 696 identified records, 61 full-text articles were screened and 34 were included. In total, 5 randomized controlled trials (RCTs) (n = 322), 12 phase I/II trials (n = 287), 6 observational studies (n = 7,599), and 11 case reports (n = 267) were identified. Because of study heterogeneity, no meta-analyses were performed. No RCTs reported any statistically significant improvements in overall or progression-free survival or reduced toxicity with ascorbate relative to control arm. Evidence for ascorbate’s antitumor effects was limited to case reports and observational and uncontrolled studies. Conclusion. There is no high-quality evidence to suggest that ascorbate supplementation in cancer patients either enhances the antitumor effects of chemotherapy or reduces its toxicity. Given the high financial and time costs to patients of this treatment, high-quality placebo-controlled trials are needed. PMID:25601965

Ethical Challenges of Randomized Violence Intervention Trials: Examining the SHARE intervention in Rakai, Uganda

PubMed Central

Wagman, Jennifer A.; Paul, Amy; Namatovu, Fredinah; Ssekubugu, Robert; Nalugoda, Fred

2016-01-01

Objective We identify complexities encountered, including unanticipated crossover between trial arms and inadequate ‘standard of care’ violence services, during a cluster randomized trial (CRT) of a community-level intimate partner violence (IPV) and HIV prevention intervention in Uganda. Methods Concepts in public health ethics - beneficence, social value of research, fairness, standard of care, and researcher responsibilities for post-trial benefits - are used to critically reflect on lessons learned and guide discussion on practical and ethical challenges of violence intervention CRTs. Results Existing ethical guidelines provide incomplete guidance for responding to unexpected crossover in CRTs providing IPV services. We struggled to balance duty of care with upholding trial integrity, and identifying and providing appropriate standard of care. While we ultimately offered short-term IPV services to controls, we faced additional challenges related to sustaining services beyond the ‘short-term’ and post-trial. Conclusion Studies evaluating community-level violence interventions, including those combined with HIV reduction strategies, are limited yet critical for developing evidence-based approaches for effectively preventing IPV. Although CRTs are a promising design, further guidance is needed to implement trials that avoid introducing tensions between validity of findings, researchers’ responsibilities to protect participants, and equitable distribution of CRT benefits. PMID:27453794

Antenatal care trial interventions: a systematic scoping review and taxonomy development of care models.

PubMed

Symon, Andrew; Pringle, Jan; Downe, Soo; Hundley, Vanora; Lee, Elaine; Lynn, Fiona; McFadden, Alison; McNeill, Jenny; Renfrew, Mary J; Ross-Davie, Mary; van Teijlingen, Edwin; Whitford, Heather; Alderdice, Fiona

2017-01-06

Antenatal care models vary widely around the world, reflecting local contexts, drivers and resources. Randomised controlled trials (RCTs) have tested the impact of multi-component antenatal care interventions on service delivery and outcomes in many countries since the 1980s. Some have applied entirely new schemes, while others have modified existing care delivery approaches. Systematic reviews (SRs) indicate that some specific antenatal interventions are more effective than others; however the causal mechanisms leading to better outcomes are poorly understood, limiting implementation and future research. As a first step in identifying what might be making the difference we conducted a scoping review of interventions tested in RCTs in order to establish a taxonomy of antenatal care models. A protocol-driven systematic search was undertaken of databases for RCTs and SRs reporting antenatal care interventions. Results were unrestricted by time or locality, but limited to English language. Key characteristics of both experimental and control interventions in the included trials were mapped using SPIO (Study design; Population; Intervention; Outcomes) criteria and the intervention and principal outcome measures were described. Commonalities and differences between the components that were being tested in each study were identified by consensus, resulting in a comprehensive description of emergent models for antenatal care interventions. Of 13,050 articles retrieved, we identified 153 eligible articles including 130 RCTs in 34 countries. The interventions tested in these trials varied from the number of visits to the location of care provision, and from the content of care to the professional/lay group providing that care. In most studies neither intervention nor control arm was well described. Our analysis of the identified trials of antenatal care interventions produced the following taxonomy: Universal provision model (for all women irrespective of health state or complications); Restricted 'lower-risk'-based provision model (midwifery-led or reduced/flexible visit approach for healthy women); Augmented provision model (antenatal care as in Universal provision above but augmented by clinical, educational or behavioural intervention); Targeted 'higher-risk'-based provision model (for woman with defined clinical or socio-demographic risk factors). The first category was most commonly tested in low-income countries (i.e. resource-poor settings), particularly in Asia. The other categories were tested around the world. The trials included a range of care providers, including midwives, nurses, doctors, and lay workers. Interventions can be defined and described in many ways. The intended antenatal care population group proved the simplest and most clinically relevant way of distinguishing trials which might otherwise be categorised together. Since our review excluded non-trial interventions, the taxonomy does not represent antenatal care provision worldwide. It offers a stable and reproducible approach to describing the purpose and content of models of antenatal care which have been tested in a trial. It highlights a lack of reported detail of trial interventions and usual care processes. It provides a baseline for future work to examine and test the salient characteristics of the most effective models, and could also help decision-makers and service planners in planning implementation.

Hip fracture risk in relation to vitamin D supplementation and serum 25-hydroxyvitamin D levels: a systematic review and meta-analysis of randomised controlled trials and observational studies

PubMed Central

2010-01-01

Background Vitamin D supplementation for fracture prevention is widespread despite conflicting interpretation of relevant randomised controlled trial (RCT) evidence. This study summarises quantitatively the current evidence from RCTs and observational studies regarding vitamin D, parathyroid hormone (PTH) and hip fracture risk. Methods We undertook separate meta-analyses of RCTs examining vitamin D supplementation and hip fracture, and observational studies of serum vitamin D status (25-hydroxyvitamin D (25(OH)D) level), PTH and hip fracture. Results from RCTs were combined using the reported hazard ratios/relative risks (RR). Results from case-control studies were combined using the ratio of 25(OH)D and PTH measurements of hip fracture cases compared with controls. Original published studies of vitamin D, PTH and hip fracture were identified through PubMed and Web of Science databases, searches of reference lists and forward citations of key papers. Results The seven eligible RCTs identified showed no significant difference in hip fracture risk in those randomised to cholecalciferol or ergocalciferol supplementation versus placebo/control (RR = 1.13[95%CI 0.98-1.29]; 801 cases), with no significant difference between trials of <800 IU/day and ≥800 IU/day. The 17 identified case-control studies found 33% lower serum 25(OH)D levels in cases compared to controls, based on 1903 cases. This difference was significantly greater in studies with population-based compared to hospital-based controls (χ21 (heterogeneity) = 51.02, p < 0.001) and significant heterogeneity was present overall (χ216 (heterogeneity) = 137.9, p < 0.001). Serum PTH levels in hip fracture cases did not differ significantly from controls, based on ten case-control studies with 905 cases (χ29 (heterogeneity) = 149.68, p < 0.001). Conclusions Neither higher nor lower dose vitamin D supplementation prevented hip fracture. Randomised and observational data on vitamin D and hip fracture appear to differ. The reason for this is unclear; one possible explanation is uncontrolled confounding in observational studies. Post-fracture PTH levels are unrelated to hip fracture risk. PMID:20540727

Physiotherapy for adult patients with critical illness: recommendations of the European Respiratory Society and European Society of Intensive Care Medicine Task Force on Physiotherapy for Critically Ill Patients.

PubMed

Gosselink, R; Bott, J; Johnson, M; Dean, E; Nava, S; Norrenberg, M; Schönhofer, B; Stiller, K; van de Leur, H; Vincent, J L

2008-07-01

The Task Force reviewed and discussed the available literature on the effectiveness of physiotherapy for acute and chronic critically ill adult patients. Evidence from randomized controlled trials or meta-analyses was limited and most of the recommendations were level C (evidence from uncontrolled or nonrandomized trials, or from observational studies) and D (expert opinion). However, the following evidence-based targets for physiotherapy were identified: deconditioning, impaired airway clearance, atelectasis, intubation avoidance, and weaning failure. Discrepancies and lack of data on the efficacy of physiotherapy in clinical trials support the need to identify guidelines for physiotherapy assessments, in particular to identify patient characteristics that enable treatments to be prescribed and modified on an individual basis. There is a need to standardize pathways for clinical decision-making and education, to define the professional profile of physiotherapists, and increase the awareness of the benefits of prevention and treatment of immobility and deconditioning for critically ill adult patients.

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.

Contrast media extravasations in patients undergoing computerized tomography scanning: a systematic review and meta-analysis of risk factors and interventions.

PubMed

Ding, Sandrine; Meystre, Nicole Richli; Campeanu, Cosmin; Gullo, Giuseppe

2018-01-01

To identify risk factors and interventions preventing or reducing contrast medium extravasation. Computed tomography (CT) is a radiological examination essential for the diagnosis and monitoring of many diseases. It is often performed with the intravenous (IV) injection of contrast agents. Use of these products can result in a significant complication, extravasation, which is the accidental leakage of IV material into the surrounding tissue. Patients may feel a sharp pain and skin ulceration or necrosis may develop. This review considered studies that included patients (adults and children) undergoing a CT with IV administration of contrast media. The risk factors considered were patient demographics, comorbidities and medication history. This review also investigated any strategies related to: contrast agent, injection per se, material used for injection, apparatus used, healthcare professionals involved, and patient risk assessment performed by the radiology personnel. The comparators were other interventions or usual care. This review investigated randomized controlled trials and non-randomized controlled trials. When neither of these were available, other study designs, such as prospective and retrospective cohort studies, case-control studies and case series, were considered for inclusion. Primary outcomes considered were: extravasation frequency, volume, severity and complications. The databases PubMed, CINAHL, Embase, the Cochrane Register of Controlled Trials, Web of Science PsycINFO, ProQuest Dissertations and Theses A&I, TRIP Database and ClinicalTrials.gov were searched to find both published and unpublished studies from 1980 to September 2016. Papers were assessed by two independent reviewers for methodological validity using the Joanna Briggs Institute System for the Unified Management, Assessment and Review of Information (JBI SUMARI). Data were extracted using the standardized data extraction tool from JBI SUMARI. In one case, quantitative data from two cohort studies were pooled in a statistical meta-analysis. However, generally, statistical pooling was not possible due to heterogeneity of the interventions, populations of interest or outcomes. Accordingly, the findings have been presented in narrative form. Fifteen articles were selected from a total of 2151 unique studies identified. Two were randomized controlled trials and 13 were quasi-experimental and observational studies. The quality of these studies was judged to be low to moderate. Some patient characteristics, such as female sex and inpatient status, appeared to be risk factors for extravasation. Additionally, injection rate, venous access site and catheter dwelling time could affect the volume extravasated. Preliminary studies seemed to indicate the potential of extravasation detection accessories to identify extravasation and reduce the volume extravasated. The other interventions either did not result in significant reduction in the frequency/volume of extravasation, or the results were mixed across the studies. The majority of the studies included in this review evaluated the outcomes of extravasation frequency and volume. Given the quality of the primary studies, this systematic review identified only potential risk factors and interventions. It further highlighted the research gap in this area and the importance of conducting trials with solid methodological designs.

Bilingualism influences inhibitory control in auditory comprehension.

PubMed

Blumenfeld, Henrike K; Marian, Viorica

2011-02-01

Bilinguals have been shown to outperform monolinguals at suppressing task-irrelevant information. The present study aimed to identify how processing linguistic ambiguity during auditory comprehension may be associated with inhibitory control. Monolinguals and bilinguals listened to words in their native language (English) and identified them among four pictures while their eye-movements were tracked. Each target picture (e.g., hamper) appeared together with a similar-sounding within-language competitor picture (e.g., hammer) and two neutral pictures. Following each eye-tracking trial, priming probe trials indexed residual activation of target words, and residual inhibition of competitor words. Eye-tracking showed similar within-language competition across groups; priming showed stronger competitor inhibition in monolinguals than in bilinguals, suggesting differences in how inhibitory control was used to resolve within-language competition. Notably, correlation analyses revealed that inhibition performance on a nonlinguistic Stroop task was related to linguistic competition resolution in bilinguals but not in monolinguals. Together, monolingual-bilingual comparisons suggest that cognitive control mechanisms can be shaped by linguistic experience. Copyright © 2010 Elsevier B.V. All rights reserved.

Comparison of a therapeutic-only versus prophylactic platelet transfusion policy for people with congenital or acquired bone marrow failure disorders.

PubMed

Malouf, Reem; Ashraf, Asma; Hadjinicolaou, Andreas V; Doree, Carolyn; Hopewell, Sally; Estcourt, Lise J

2018-05-14

Bone marrow disorders encompass a group of diseases characterised by reduced production of red cells, white cells, and platelets, or defects in their function, or both. The most common bone marrow disorder is myelodysplastic syndrome. Thrombocytopenia, a low platelet count, commonly occurs in people with bone marrow failure. Platetet transfusions are routinely used in people with thrombocytopenia secondary to bone marrow failure disorders to treat or prevent bleeding. Myelodysplastic syndrome is currently the most common reason for receiving a platelet transfusion in some Western countries. To determine whether a therapeutic-only platelet transfusion policy (transfusion given when patient is bleeding) is as effective and safe as a prophylactic platelet transfusion policy (transfusion given to prevent bleeding according to a prespecified platelet threshold) in people with congenital or acquired bone marrow failure disorders. We searched for randomised controlled trials (RCTs), non-RCTs, and controlled before-after studies (CBAs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2017, Issue 9), Ovid MEDLINE (from 1946), Ovid Embase (from 1974), PubMed (e-publications only), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 12 October 2017. We included RCTs, non-RCTs, and CBAs that involved the transfusion of platelet concentrates (prepared either from individual units of whole blood or by apheresis any dose, frequency, or transfusion trigger) and given to treat or prevent bleeding among people with congenital or acquired bone marrow failure disorders.We excluded uncontrolled studies, cross-sectional studies, and case-control studies. We excluded cluster-RCTs, non-randomised cluster trials, and CBAs with fewer than two intervention sites and two control sites due to the risk of confounding. We included all people with long-term bone marrow failure disorders that require platelet transfusions, including neonates. We excluded studies of alternatives to platelet transfusion, or studies of people receiving intensive chemotherapy or a stem cell transplant. We used the standard methodological procedures outlined by Cochrane. Due to the absence of evidence we were unable to report on any of the review outcomes. We identified one RCT that met the inclusion criteria for this review. The study enrolled only nine adults with MDS over a three-year study duration period. The trial was terminated due to poor recruitment rate (planned recruitment 60 participants over two years). Assessment of the risk of bias was not possible for all domains. The trial was a single-centre, single-blind trial. The clinical and demographic characteristics of the participants were never disclosed. The trial outcomes relevant to this review were bleeding assessments, mortality, quality of life, and length of hospital stay, but no data were available to report on any of these outcomes.We identified no completed non-RCTs or CBAs.We identified no ongoing RCTs, non-RCTs, or CBAs. We found no evidence to determine the safety and efficacy of therapeutic platelet transfusion compared with prophylactic platelet transfusion for people with long-term bone marrow failure disorders. This review underscores the urgency of prioritising research in this area. People with bone marrow failure depend on long-term platelet transfusion support, but the only trial that assessed a therapeutic strategy was halted. There is a need for good-quality studies comparing a therapeutic platelet transfusion strategy with a prophylactic platelet transfusion strategy; such trials should include outcomes that are important to patients, such as quality of life, length of hospital admission, and risk of bleeding.

Intraoperative imaging technology to maximise extent of resection for glioma.

PubMed

Jenkinson, Michael D; Barone, Damiano Giuseppe; Bryant, Andrew; Vale, Luke; Bulbeck, Helen; Lawrie, Theresa A; Hart, Michael G; Watts, Colin

2018-01-22

Extent of resection is considered to be a prognostic factor in neuro-oncology. Intraoperative imaging technologies are designed to help achieve this goal. It is not clear whether any of these sometimes very expensive tools (or their combination) should be recommended as standard care for people with brain tumours. We set out to determine if intraoperative imaging technology offers any advantage in terms of extent of resection over standard surgery and if any one technology was more effective than another. To establish the overall effectiveness and safety of intraoperative imaging technology in resection of glioma. To supplement this review of effects, we also wished to identify cost analyses and economic evaluations as part of a Brief Economic Commentary (BEC). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 7, 2017), MEDLINE (1946 to June, week 4, 2017), and Embase (1980 to 2017, week 27). We searched the reference lists of all identified studies. We handsearched two journals, the Journal of Neuro-Oncology and Neuro-oncology, from 1991 to 2017, including all conference abstracts. We contacted neuro-oncologists, trial authors, and manufacturers regarding ongoing and unpublished trials. Randomised controlled trials evaluating people of all ages with presumed new or recurrent glial tumours (of any location or histology) from clinical examination and imaging (computed tomography (CT) or magnetic resonance imaging (MRI), or both). Additional imaging modalities (e.g. positron emission tomography, magnetic resonance spectroscopy) were not mandatory. Interventions included intraoperative MRI (iMRI), fluorescence-guided surgery, ultrasound, and neuronavigation (with or without additional image processing, e.g. tractography). Two review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a prespecified pro forma. We identified four randomised controlled trials, using different intraoperative imaging technologies: iMRI (2 trials including 58 and 14 participants, respectively); fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) (1 trial, 322 participants); and neuronavigation (1 trial, 45 participants). We identified one ongoing trial assessing iMRI with a planned sample size of 304 participants for which results are expected to be published around autumn 2018. We identified no trials for ultrasound.Meta-analysis was not appropriate due to differences in the tumours included (eloquent versus non-eloquent locations) and variations in the image guidance tools used in the control arms (usually selective utilisation of neuronavigation). There were significant concerns regarding risk of bias in all the included studies. All studies included people with high-grade glioma only.Extent of resection was increased in one trial of iMRI (risk ratio (RR) of incomplete resection 0.13, 95% confidence interval (CI) 0.02 to 0.96; 1 study, 49 participants; very low-quality evidence) and in the trial of 5-ALA (RR of incomplete resection 0.55, 95% CI 0.42 to 0.71; 1 study, 270 participants; low-quality evidence). The other trial assessing iMRI was stopped early after an unplanned interim analysis including 14 participants, therefore the trial provides very low-quality evidence. The trial of neuronavigation provided insufficient data to evaluate the effects on extent of resection.Reporting of adverse events was incomplete and suggestive of significant reporting bias (very low-quality evidence). Overall, reported events were low in most trials. There was no clear evidence of improvement in overall survival with 5-ALA (hazard ratio 0.83, 95% CI 0.62 to 1.07; 1 study, 270 participants; low-quality evidence). Progression-free survival data were not available in an appropriate format for analysis. Data for quality of life were only available for one study and suffered from significant attrition bias (very low-quality evidence). Intra-operative imaging technologies, specifically iMRI and 5-ALA, may be of benefit in maximising extent of resection in participants with high grade glioma. However, this is based on low to very low quality evidence, and is therefore very uncertain. The short- and long-term neurological effects are uncertain. Effects of image-guided surgery on overall survival, progression-free survival, and quality of life are unclear. A brief economic commentary found limited economic evidence for the equivocal use of iMRI compared with conventional surgery. In terms of costs, a non-systematic review of economic studies suggested that compared with standard surgery use of image-guided surgery has an uncertain effect on costs and that 5-aminolevulinic acid was more costly. Further research, including studies of ultrasound-guided surgery, is needed.

Evidence-based care of older people with suspected cognitive impairment in general practice: protocol for the IRIS cluster randomised trial.

PubMed

McKenzie, Joanne E; French, Simon D; O'Connor, Denise A; Mortimer, Duncan S; Browning, Colette J; Russell, Grant M; Grimshaw, Jeremy M; Eccles, Martin P; Francis, Jill J; Michie, Susan; Murphy, Kerry; Kossenas, Fiona; Green, Sally E

2013-08-19

Dementia is a common and complex condition. Evidence-based guidelines for the management of people with dementia in general practice exist; however, detection, diagnosis and disclosure of dementia have been identified as potential evidence-practice gaps. Interventions to implement guidelines into practice have had varying success. The use of theory in designing implementation interventions has been limited, but is advocated because of its potential to yield more effective interventions and aid understanding of factors modifying the magnitude of intervention effects across trials. This protocol describes methods of a randomised trial that tests a theory-informed implementation intervention that, if effective, may provide benefits for patients with dementia and their carers. This trial aims to estimate the effectiveness of a theory-informed intervention to increase GPs' (in Victoria, Australia) adherence to a clinical guideline for the detection, diagnosis, and management of dementia in general practice, compared with providing GPs with a printed copy of the guideline. Primary objectives include testing if the intervention is effective in increasing the percentage of patients with suspected cognitive impairment who receive care consistent with two key guideline recommendations: receipt of a i) formal cognitive assessment, and ii) depression assessment using a validated scale (primary outcomes for the trial). The design is a parallel cluster randomised trial, with clusters being general practices. We aim to recruit 60 practices per group. Practices will be randomised to the intervention and control groups using restricted randomisation. Patients meeting the inclusion criteria, and GPs' detection and diagnosis behaviours directed toward these patients, will be identified and measured via an electronic search of the medical records nine months after the start of the intervention. Practitioners in the control group will receive a printed copy of the guideline. In addition to receipt of the printed guideline, practitioners in the intervention group will be invited to participate in an interactive, opinion leader-led, educational face-to-face workshop. The theory-informed intervention aims to address identified barriers to and enablers of implementation of recommendations. Researchers responsible for identifying the cohort of patients with suspected cognitive impairment, and their detection and diagnosis outcomes, will be blind to group allocation. Australian New Zealand Clinical Trials Registry: ACTRN12611001032943 (date registered 28 September, 2011).

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

Is your prescription of distance running shoes evidence-based?

PubMed

Richards, C E; Magin, P J; Callister, R

2009-03-01

To determine whether the current practice of prescribing distance running shoes featuring elevated cushioned heels and pronation control systems tailored to the individual's foot type is evidence-based. MEDLINE (1950-May 2007), CINAHL (1982-May 2007), EMBASE (1980-May 2007), PsychInfo (1806-May 2007), Cochrane Database of Systematic Reviews (2(nd) Quarter 2007), Cochrane Central Register of Controlled trials (2(nd) Quarter 2007), SPORTSDiscus (1985-May 2007) and AMED (1985-May 2007). English language articles were identified via keyword and medical subject headings (MeSH) searches of the above electronic databases. With these searches and the subsequent review process, controlled trials or systematic reviews were sought in which the study population included adult recreational or competitive distance runners, the exposure was distance running, the intervention evaluated was a running shoe with an elevated cushioned heel and pronation control systems individualised to the wearer's foot type, and the outcome measures included either running injury rates, distance running performance, osteoarthritis risk, physical activity levels, or overall health and wellbeing. The quality of these studies and their findings were then evaluated. No original research that met the study criteria was identified either directly or via the findings of the six systematic reviews identified. The prescription of this shoe type to distance runners is not evidence-based.

Therapeutic touch for anxiety disorders.

PubMed

Robinson, J; Biley, F C; Dolk, H

2007-07-18

Anxiety disorders are a common occurrence in today's society. There is interest from the community in the use of complementary therapies for anxiety disorders. This review examined the currently available evidence supporting the use of therapeutic touch in treating anxiety disorders. To examine the efficacy and adverse effects of therapeutic touch for anxiety disorders. We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References) (search date 13/01/06), the Controlled Trials website and Dissertation Abstracts International. Searches of reference lists of retrieved papers were also carried out and experts in the field were contacted. Inclusion criteria included all published and unpublished randomised and quasi-randomised controlled trials comparing therapeutic touch with sham (mimic) TT, pharmacological therapy, psychological treatment, other treatment or no treatment /waiting list. The participants included adults with an anxiety disorder defined by the Diagnostic and Statistical Manual (DSM-IV),the International Classification of Diseases (ICD-10), validated diagnostic instruments, or other validated clinician or self-report instruments. Two review authors independently applied inclusion criteria. Further information was sought from trialists where papers contained insufficient information to make a decision about eligibility. No randomised or quasi-randomised controlled trials of therapeutic touch for anxiety disorders were identified. Given the high prevalence of anxiety disorders and the current paucity of evidence on therapeutic touch in this population, there is a need for well conducted randomised controlled trials to examine the effectiveness of therapeutic touch for anxiety disorders.

The effect of magnesium supplementation on blood pressure in individuals with insulin resistance, prediabetes, or noncommunicable chronic diseases: a meta-analysis of randomized controlled trials.

PubMed

Dibaba, Daniel T; Xun, Pengcheng; Song, Yiqing; Rosanoff, Andrea; Shechter, Michael; He, Ka

2017-09-01

Background: To our knowledge, the effect of magnesium supplementation on blood pressure (BP) in individuals with preclinical or noncommunicable diseases has not been previously investigated in a meta-analysis, and the findings from randomized controlled trials (RCTs) have been inconsistent. Objective: We sought to determine the pooled effect of magnesium supplementation on BP in participants with preclinical or noncommunicable diseases. Design: We identified RCTs that were published in English before May 2017 that examined the effect of magnesium supplementation on BP in individuals with preclinical or noncommunicable diseases through PubMed, ScienceDirect, Cochrane, clinicaltrials.gov, SpringerLink, and Google Scholar databases as well as the reference lists from identified relevant articles. Random- and fixed-effects models were used to estimate the pooled standardized mean differences (SMDs) with 95% CIs in changes in BP from baseline to the end of the trial in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) between the magnesium-supplementation group and the control group. Results: Eleven RCTs that included 543 participants with follow-up periods that ranged from 1 to 6 mo (mean: 3.6 mo) were included in this meta-analysis. The dose of elemental magnesium that was used in the trials ranged from 365 to 450 mg/d. All studies reported BP at baseline and the end of the trial. The weighted overall effects indicated that the magnesium-supplementation group had a significantly greater reduction in both SBP (SMD: -0.20; 95% CI: -0.37, -0.03) and DBP (SMD: -0.27; 95% CI: -0.52, -0.03) than did the control group. Magnesium supplementation resulted in a mean reduction of 4.18 mm Hg in SBP and 2.27 mm Hg in DBP. Conclusion: The pooled results suggest that magnesium supplementation significantly lowers BP in individuals with insulin resistance, prediabetes, or other noncommunicable chronic diseases. © 2017 American Society for Nutrition.

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.

Data-driven risk identification in phase III clinical trials using central statistical monitoring.

PubMed

Timmermans, Catherine; Venet, David; Burzykowski, Tomasz

2016-02-01

Our interest lies in quality control for clinical trials, in the context of risk-based monitoring (RBM). We specifically study the use of central statistical monitoring (CSM) to support RBM. Under an RBM paradigm, we claim that CSM has a key role to play in identifying the "risks to the most critical data elements and processes" that will drive targeted oversight. In order to support this claim, we first see how to characterize the risks that may affect clinical trials. We then discuss how CSM can be understood as a tool for providing a set of data-driven key risk indicators (KRIs), which help to organize adaptive targeted monitoring. Several case studies are provided where issues in a clinical trial have been identified thanks to targeted investigation after the identification of a risk using CSM. Using CSM to build data-driven KRIs helps to identify different kinds of issues in clinical trials. This ability is directly linked with the exhaustiveness of the CSM approach and its flexibility in the definition of the risks that are searched for when identifying the KRIs. In practice, a CSM assessment of the clinical database seems essential to ensure data quality. The atypical data patterns found in some centers and variables are seen as KRIs under a RBM approach. Targeted monitoring or data management queries can be used to confirm whether the KRIs point to an actual issue or not.

Protocol for a feasibility cluster randomised controlled trial of a peer-led school-based intervention to increase the physical activity of adolescent girls (PLAN-A).

PubMed

Sebire, Simon J; Edwards, Mark J; Campbell, Rona; Jago, Russell; Kipping, Ruth; Banfield, Kathryn; Tomkinson, Keeley; Garfield, Kirsty; Lyons, Ronan A; Simon, Joanne; Blair, Peter S; Hollingworth, William

2016-01-01

Physical activity levels are low amongst adolescent girls, and this population faces specific barriers to being active. Peer influences on health behaviours are important in adolescence and peer-led interventions might hold promise to change behaviour. This paper describes the protocol for a feasibility cluster randomised controlled trial of Peer-Led physical Activity iNtervention for Adolescent girls (PLAN-A), a peer-led intervention aimed at increasing adolescent girls' physical activity levels. A two-arm cluster randomised feasibility trial will be conducted in six secondary schools (intervention n  = 4; control n  = 2) with year 8 (12-13 years old) girls. The intervention will operate at a year group level and consist of year 8 girls nominating influential peers within their year group to become peer-supporters. Approximately 15 % of the cohort will receive 3 days of training about physical activity and interpersonal communication skills. Peer-supporters will then informally diffuse messages about physical activity amongst their friends for 10 weeks. Data will be collected at baseline (time 0 (T0)), immediately after the intervention (time 1 (T1)) and 12 months after baseline measures (time 2 (T2)). In this feasibility trial, the primary interest is in the recruitment of schools and participants (both year 8 girls and peer-supporters), delivery and receipt of the intervention, data provision rates and identifying the cost categories for future economic analysis. Physical activity will be assessed using 7-day accelerometry, with the likely primary outcome in a fully-powered trial being daily minutes of moderate-to-vigorous physical activity. Participants will also complete psychosocial questionnaires at each time point: assessing motivation, self-esteem and peer physical activity norms. Data analysis will be largely descriptive and focus on recruitment, attendance and data provision rates. The findings will inform the sample size required for a definitive trial. A detailed process evaluation using qualitative and quantitative methods will be conducted with a variety of stakeholders (i.e. pupils, parents, teachers and peer-supporter trainers) to identify areas of success and necessary improvements prior to proceeding to a definitive trial. This paper describes the protocol for the PLAN-A feasibility cluster randomised controlled trial which will provide the information necessary to design a fully-powered trial should PLAN-A demonstrate evidence of promise. ISRCTN12543546.

High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Transplantation in Metastatic Breast Cancer: Overview of Six Randomized Trials

PubMed Central

Berry, Donald A.; Ueno, Naoto T.; Johnson, Marcella M.; Lei, Xiudong; Caputo, Jean; Smith, Dori A.; Yancey, Linda J.; Crump, Michael; Stadtmauer, Edward A.; Biron, Pierre; Crown, John P.; Schmid, Peter; Lotz, Jean-Pierre; Rosti, Giovanni; Bregni, Marco; Demirer, Taner

2011-01-01

Purpose High doses of effective chemotherapy are compelling if they can be delivered safely. Substantial interest in supporting high-dose chemotherapy with bone marrow or autologous hematopoietic stem-cell transplantation in the 1980s and 1990s led to the initiation of randomized trials to evaluate its effect in the treatment of metastatic breast cancer. Methods We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support. We assembled a single database containing individual patient information from these trials. The primary analysis of overall survival was a log-rank test comparing high dose versus control. We also used Cox proportional hazards regression, adjusting for known covariates. We addressed potential treatment differences within subsets of patients. Results The effect of high-dose chemotherapy on overall survival was not statistically different (median, 2.16 v 2.02 years; P = .08). A statistically significant advantage in progression-free survival (median, 0.91 v 0.69 years) did not translate into survival benefit. Subset analyses found little evidence that there are groups of patients who might benefit from high-dose chemotherapy with hematopoietic support. Conclusion Overall survival of patients with metastatic breast cancer in the six randomized trials was not significantly improved by high-dose chemotherapy; any benefit from high doses was small. No identifiable subset of patients seems to benefit from high-dose chemotherapy. PMID:21768454

Effectiveness of Facebook-Delivered Lifestyle Counselling and Physical Activity Self-Monitoring on Physical Activity and Body Mass Index in Overweight and Obese Adolescents: A Randomized Controlled Trial.

PubMed

Ruotsalainen, Heidi; Kyngäs, Helvi; Tammelin, Tuija; Heikkinen, Hanna; Kääriäinen, Maria

2015-01-01

Background. The aim was to evaluate the effects of a 12-week, Facebook-delivered lifestyle counselling intervention, with or without physical activity self-monitoring, on physical activity and body mass index (BMI) in overweight and obese 13-16-year-old adolescents. Methods. Three-arm randomized controlled trial. Participants (n = 46) were randomly assigned to intervention and control groups: one group received Facebook-delivered lifestyle counselling and monitoring of their physical activity (Fb + Act, n = 15), whereas a second experimental group received the same Facebook-delivered lifestyle counselling without self-monitoring (Fb, n = 16) and a third group served as the control group (n = 15). Objective and self-reported physical activity assessment were used. Nonparametric statistical tests were used. Results. There were no significant intervention effects in terms of changes in physical activity levels or BMI from baseline to the 12-week postintervention measurements between the intervention and control groups. The Fb + Act group had lower sedentary time on weekdays compared to the control group during postintervention measurements (p = 0.021), but there was no interaction between time and group. Conclusions. Interventions were not effective at increasing physical activity in overweight and obese adolescents. Before implementing such interventions, more evaluations on their effectiveness are needed. This trial is registered with ClinicalTrials.gov identifier NCT02295761 (2014-11-17).

Z-drug for schizophrenia: A systematic review and meta-analysis.

PubMed

Kishi, Taro; Inada, Ken; Matsui, Yuki; Iwata, Nakao

2017-10-01

No systematic reviews and meta-analyses on the use of Z-drug for schizophrenia are available. Randomized, placebo-controlled, or non-pharmacological intervention-controlled trials published before 03/20/2017 were retrieved from major healthcare databases and clinical trial registries. A meta-analysis including only randomized, placebo-controlled trials was performed. Efficacy outcomes were measured as improvement in overall schizophrenia symptoms, total sleep time, and wake after sleep onset. Safety/acceptability outcomes were discontinuation rate and individual adverse events. Four trials [1 alpidem placebo-controlled study (n=66), 2 eszopiclone placebo-controlled studies (n=60), and 1 eszopiclone, shallow needling-controlled study (n=96)] were identified. The meta-analysis showed no significant differences in any outcome between pooled Z-drug and placebo treatment groups. For individual studies, alpidem was superior to placebo in improving the overall schizophrenia symptoms. One of the eszopiclone studies showed that eszopiclone was superior to placebo in improving the Insomnia Severity Index scores. Another eszopiclone study showed that eszopiclone did not differ from shallow needling therapy in improving both schizophrenia- and insomnia-related symptoms. Although this study failed to show significant benefits for the use of Z-drug in the treatment of schizophrenia, it showed that short-term use of eszopiclone is an acceptable method for treating persistent insomnia among these patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison between publicly accessible publications, registries, and protocols of phase III trials indicated persistence of selective outcome reporting.

PubMed

Zhang, Sheng; Liang, Fei; Li, Wenfeng

2017-11-01

The decision to make protocols of phase III randomized controlled trials (RCTs) publicly accessible by leading journals was a landmark event in clinical trial reporting. Here, we compared primary outcomes defined in protocols with those in publications describing the trials and in trial registration. We identified phase III RCTs published between January 1, 2012, and June 30, 2015, in The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, and The BMJ with available protocols. Consistency in primary outcomes between protocols and registries (articles) was evaluated. We identified 299 phase III RCTs with available protocols in this analysis. Out of them, 25 trials (8.4%) had some discrepancy for primary outcomes between publications and protocols. Types of discrepancies included protocol-defined primary outcome reported as nonprimary outcome in publication (11 trials, 3.7%), protocol-defined primary outcome omitted in publication (10 trials, 3.3%), new primary outcome introduced in publication (8 trials, 2.7%), protocol-defined nonprimary outcome reported as primary outcome in publication (4 trials, 1.3%), and different timing of assessment of primary outcome (4 trials, 1.3%). Out of trials with discrepancies in primary outcome, 15 trials (60.0%) had discrepancies that favored statistically significant results. Registration could be seen as a valid surrogate of protocol in 237 of 299 trials (79.3%) with regard to primary outcome. Despite unrestricted public access to protocols, selective outcome reporting persists in a small fraction of phase III RCTs. Only studies from four leading journals were included, which may cause selection bias and limit the generalizability of this finding. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy of umbilical cord cleansing with a single application of 4% chlorhexidine for the prevention of newborn infections in Uganda: study protocol for a randomized controlled trial.

PubMed

Nankabirwa, Victoria; Tylleskär, Thorkild; Tumuhamye, Josephine; Tumwine, James K; Ndeezi, Grace; Martines, José C; Sommerfelt, Halvor

2017-07-12

Yearly, nearly all the estimated worldwide 2.7 million neonatal deaths occur in low- and middle-income countries. Infections, including those affecting the umbilical cord (omphalitis), are a significant factor in approximately a third of these deaths. In fact, the odds of all-cause mortality are 46% higher among neonates with omphalitis than in those without. Five large randomized controlled trials in Asia and Sub-Saharan Africa (SSA) have examined the effect of multiple cord stump applications with 4% chlorhexidine (CHX) for at least 7 days on the risk of omphalitis and neonatal death. These studies, all community-based, show that multiple CHX applications reduced the risk of omphalitis. Of these trials, only one study from South Asia (the Bangladeshi study) and none from Africa examined the effect of a single application of CHX as soon as possible after birth. In this Bangladeshi trial, CHX led to a reduction in the risk of mild-moderate omphalitis and neonatal death. It is important, in an African setting, to explore the effect of a single application among health-facility births. A single application is programmatically much simpler to implement than daily applications for 7 days. Therefore, our study compares umbilical cord cleansing with a single application of 4% CHX at birth with dry cord care among Ugandan babies born in health facilities, on the risk of omphalitis and severe neonatal illness. The CHX study is a facility-based, individually randomized controlled trial that will be conducted among 4760 newborns in Uganda. The primary outcomes are severe illness and omphalitis during the neonatal period. Analysis will be by intention-to-treat. This study will provide novel evidence, from a Sub-Saharan African setting, of the effect of umbilical cord cleansing with a single application of 4% CHX at birth and identify modifiable risk factors for omphalitis. ClinicalTrials.gov, identifier: NCT02606565 . Registered on 12 November 2015.

Arterial Obstruction on Computed Tomographic or Magnetic Resonance Angiography and Response to Intravenous Thrombolytics in Ischemic Stroke

PubMed Central

Mair, Grant; von Kummer, Rüdiger; Adami, Alessandro; White, Philip M.; Adams, Matthew E.; Yan, Bernard; Demchuk, Andrew M.; Farrall, Andrew J.; Sellar, Robin J.; Sakka, Eleni; Palmer, Jeb; Perry, David; Lindley, Richard I.; Sandercock, Peter A.G.

2017-01-01

Background and Purpose— Computed tomographic angiography and magnetic resonance angiography are used increasingly to assess arterial patency in patients with ischemic stroke. We determined which baseline angiography features predict response to intravenous thrombolytics in ischemic stroke using randomized controlled trial data. Methods— We analyzed angiograms from the IST-3 (Third International Stroke Trial), an international, multicenter, prospective, randomized controlled trial of intravenous alteplase. Readers, masked to clinical, treatment, and outcome data, assessed prerandomization computed tomographic angiography and magnetic resonance angiography for presence, extent, location, and completeness of obstruction and collaterals. We compared angiography findings to 6-month functional outcome (Oxford Handicap Scale) and tested for interactions with alteplase, using ordinal regression in adjusted analyses. We also meta-analyzed all available angiography data from other randomized controlled trials of intravenous thrombolytics. Results— In IST-3, 300 patients had prerandomization angiography (computed tomographic angiography=271 and magnetic resonance angiography=29). On multivariable analysis, more extensive angiographic obstruction and poor collaterals independently predicted poor outcome (P<0.01). We identified no significant interaction between angiography findings and alteplase effect on Oxford Handicap Scale (P≥0.075) in IST-3. In meta-analysis (5 trials of alteplase or desmoteplase, including IST-3, n=591), there was a significantly increased benefit of thrombolytics on outcome (odds ratio>1 indicates benefit) in patients with (odds ratio, 2.07; 95% confidence interval, 1.18–3.64; P=0.011) versus without (odds ratio, 0.88; 95% confidence interval, 0.58–1.35; P=0.566) arterial obstruction (P for interaction 0.017). Conclusions— Intravenous thrombolytics provide benefit to stroke patients with computed tomographic angiography or magnetic resonance angiography evidence of arterial obstruction, but the sample was underpowered to demonstrate significant treatment benefit or harm among patients with apparently patent arteries. Clinical Trial Registration— URL: http://www.isrctn.com. Unique identifier: ISRCTN25765518. PMID:28008093

PERFECTED enhanced recovery (PERFECT-ER) care versus standard acute care for patients admitted to acute settings with hip fracture identified as experiencing confusion: study protocol for a feasibility cluster randomized controlled trial.

PubMed

Hammond, Simon P; Cross, Jane L; Shepstone, Lee; Backhouse, Tamara; Henderson, Catherine; Poland, Fiona; Sims, Erika; MacLullich, Alasdair; Penhale, Bridget; Howard, Robert; Lambert, Nigel; Varley, Anna; Smith, Toby O; Sahota, Opinder; Donell, Simon; Patel, Martyn; Ballard, Clive; Young, John; Knapp, Martin; Jackson, Stephen; Waring, Justin; Leavey, Nick; Howard, Gregory; Fox, Chris

2017-12-04

Health and social care provision for an ageing population is a global priority. Provision for those with dementia and hip fracture has specific and growing importance. Older people who break their hip are recognised as exceptionally vulnerable to experiencing confusion (including but not exclusively, dementia and/or delirium and/or cognitive impairment(s)) before, during or after acute admissions. Older people experiencing hip fracture and confusion risk serious complications, linked to delayed recovery and higher mortality post-operatively. Specific care pathways acknowledging the differences in patient presentation and care needs are proposed to improve clinical and process outcomes. This protocol describes a multi-centre, feasibility, cluster-randomised, controlled trial (CRCT) to be undertaken across ten National Health Service hospital trusts in the UK. The trial will explore the feasibility of undertaking a CRCT comparing the multicomponent PERFECTED enhanced recovery intervention (PERFECT-ER), which acknowledges the differences in care needs of confused older patients experiencing hip fracture, with standard care. The trial will also have an integrated process evaluation to explore how PERFECT-ER is implemented and interacts with the local context. The study will recruit 400 hip fracture patients identified as experiencing confusion and will also recruit "suitable informants" (individuals in regular contact with participants who will complete proxy measures). We will also recruit NHS professionals for the process evaluation. This mixed methods design will produce data to inform a definitive evaluation of the intervention via a large-scale pragmatic randomised controlled trial (RCT). The trial will provide a preliminary estimate of potential efficacy of PERFECT-ER versus standard care; assess service delivery variation, inform primary and secondary outcome selection, generate estimates of recruitment and retention rates, data collection difficulties, and completeness of outcome data and provide an indication of potential economic benefits. The process evaluation will enhance knowledge of implementation delivery and receipt. ISRCTN, 99336264 . Registered on 5 September 2016.

Psycho-educational interventions for children and young people with Type 1 Diabetes in the UK: How effective are they? A systematic review and meta-analysis

PubMed Central

Hesketh, Kathryn R.; Amin, Rakesh; Paes, Veena Mazarello; Viner, Russell M.; Stephenson, Terence

2017-01-01

Aims To synthesise evidence from UK-based randomised trials of psycho-educational interventions in children and young people (CYP) with Type 1 Diabetes (T1D) to inform the evidence-base for adoption of such interventions into the NHS. Methods We searched Medline, Embase, Cochrane, PsycINFO, CINAHL, and Web of Science up to March 2016. Two reviewers independently selected UK-based randomised trials comparing psycho-educational interventions for improving management of T1D for CYP with a control group of usual care or attention control. The main outcome was glycaemic control measured by percentage of glycated haemoglobin (HbA1c); secondary outcomes included psychosocial functioning, diabetes knowledge, adverse and other clinical outcomes. A narrative synthesis and meta-analysis were conducted. Pooled effect sizes of standardised mean difference (SMD) were calculated. Results Ten eligible trials of three educational and seven psycho-educational interventions were identified. Most interventions were delivered by non-psychologists and targeted adolescents with more than one year duration of diabetes. Meta-analysis of nine of these trials (N = 1,838 participants) showed a non-significant reduction in HbA1c attributable to the intervention (pooled SMD = -0.06, 95% CI: -0.21 to 0.09). Psycho-educational interventions aiming to increase children’s self-efficacy had a moderate, beneficial effect (SMD = 0.50, 95% CI: 0.13 to 0.87). No benefits on diabetes knowledge and other indicators of psychosocial functioning were identified. Conclusions There is insufficient evidence to recommend the use of particular psycho-educational programme for CYP with T1D in the UK. Further trials with sufficient power and reporting standards are needed. Future trials could consider active involvement of psychological specialists in the delivery of psychologically informed interventions and implementation of psycho-educational interventions earlier in the course of the disease. Systematic review registration PROSPERO CRD42015010701 PMID:28665946

Brain-computer interfaces for post-stroke motor rehabilitation: a meta-analysis.

PubMed

Cervera, María A; Soekadar, Surjo R; Ushiba, Junichi; Millán, José Del R; Liu, Meigen; Birbaumer, Niels; Garipelli, Gangadhar

2018-05-01

Brain-computer interfaces (BCIs) can provide sensory feedback of ongoing brain oscillations, enabling stroke survivors to modulate their sensorimotor rhythms purposefully. A number of recent clinical studies indicate that repeated use of such BCIs might trigger neurological recovery and hence improvement in motor function. Here, we provide a first meta-analysis evaluating the clinical effectiveness of BCI-based post-stroke motor rehabilitation. Trials were identified using MEDLINE, CENTRAL, PEDro and by inspection of references in several review articles. We selected randomized controlled trials that used BCIs for post-stroke motor rehabilitation and provided motor impairment scores before and after the intervention. A random-effects inverse variance method was used to calculate the summary effect size. We initially identified 524 articles and, after removing duplicates, we screened titles and abstracts of 473 articles. We found 26 articles corresponding to BCI clinical trials, of these, there were nine studies that involved a total of 235 post-stroke survivors that fulfilled the inclusion criterion (randomized controlled trials that examined motor performance as an outcome measure) for the meta-analysis. Motor improvements, mostly quantified by the upper limb Fugl-Meyer Assessment (FMA-UE), exceeded the minimal clinically important difference (MCID=5.25) in six BCI studies, while such improvement was reached only in three control groups. Overall, the BCI training was associated with a standardized mean difference of 0.79 (95% CI: 0.37 to 1.20) in FMA-UE compared to control conditions, which is in the range of medium to large summary effect size. In addition, several studies indicated BCI-induced functional and structural neuroplasticity at a subclinical level. This suggests that BCI technology could be an effective intervention for post-stroke upper limb rehabilitation. However, more studies with larger sample size are required to increase the reliability of these results.

Effects of life review on mental health and well-being among cancer patients: A systematic review.

PubMed

Zhang, Xiaoling; Xiao, Huimin; Chen, Ying

2017-09-01

Cancer patients often experience psychological distress. Life review has increasingly been used to enhance their mental health and well-being. However, no systematic review has synthesized the evidence, and its effects remain unclear. To examine and synthesize the best available evidence on the effects of life review on mental health and well-being among cancer patients. Systematic review of randomized controlled trials and clinical controlled trials. Twelve electronic databases were searched for published studies reported in English or Chinese, from inception to September 2016. Other supplementary sources, such as related websites, professional books, reference lists, and author contacts were also used for published or unpublished studies. A comprehensive literature search was conducted to identify eligible randomized controlled trials or clinical controlled trials about the effects of life review on cancer patients. Study selection, quality assessment, and data extraction were independently performed by two reviewers. The results were synthesized without meta-analysis in this review. Fifteen studies (899 participants) were identified; of that total, nine studies were rated as strong in quality, while six studies were of moderate quality. In addition to structured life review interviews, other elements such as memory prompts and a legacy product were integrated into life review programs. A majority of studies indicated that life review programs benefited cancer patients by reducing depression and anxiety, as well as improving their sense of hope, self-esteem and quality of life. Life review can improve mental health and well-being among cancer patients. This suggests that life review can be integrated into typical cancer treatment to enhance patients' mental health and well-being. More research with rigorous design is necessary to further explore the effects of life review. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aripiprazole in the Maintenance Treatment of Bipolar Disorder: A Critical Review of the Evidence and Its Dissemination into the Scientific Literature

PubMed Central

Jureidini, Jon N.; Parry, Peter I.; Spielmans, Glen I.; Healy, David

2011-01-01

Background Aripiprazole, a second-generation antipsychotic medication, has been increasingly used in the maintenance treatment of bipolar disorder and received approval from the U.S. Food and Drug Administration for this indication in 2005. Given its widespread use, we sought to critically review the evidence supporting the use of aripiprazole in the maintenance treatment of bipolar disorder and examine how that evidence has been disseminated in the scientific literature. Methods and Findings We systematically searched multiple databases to identify double-blind, randomized controlled trials of aripiprazole for the maintenance treatment of bipolar disorder while excluding other types of studies, such as open-label, acute, and adjunctive studies. We then used a citation search to identify articles that cited these trials and rated the quality of their citations. Our evidence search protocol identified only two publications, both describing the results of a single trial conducted by Keck et al., which met criteria for inclusion in this review. We describe four issues that limit the interpretation of that trial as supporting the use of aripiprazole for bipolar maintenance: (1) insufficient duration to demonstrate maintenance efficacy; (2) limited generalizability due to its enriched sample; (3) possible conflation of iatrogenic adverse effects of abrupt medication discontinuation with beneficial effects of treatment; and (4) a low overall completion rate. Our citation search protocol yielded 80 publications that cited the Keck et al. trial in discussing the use of aripiprazole for bipolar maintenance. Of these, only 24 (30%) mentioned adverse events reported and four (5%) mentioned study limitations. Conclusions A single trial by Keck et al. represents the entirety of the literature on the use of aripiprazole for the maintenance treatment of bipolar disorder. Although careful review identifies four critical limitations to the trial's interpretation and overall utility, the trial has been uncritically cited in the subsequent scientific literature. Please see later in the article for the Editors' Summary PMID:21559324

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol.

PubMed

Sandilands, Euan A; Cameron, Sharon; Paterson, Frances; Donaldson, Sam; Briody, Lesley; Crowe, Jane; Donnelly, Julie; Thompson, Adrian; Johnston, Neil R; Mackenzie, Ivor; Uren, Neal; Goddard, Jane; Webb, David J; Megson, Ian L; Bateman, Nicholas; Eddleston, Michael

2012-02-03

Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18.

Classroom based cognitive behavioural therapy in reducing symptoms of depression in high risk adolescents: pragmatic cluster randomised controlled trial

PubMed Central

Sayal, Kapil; Phillips, Rhiannon; Taylor, John A; Spears, Melissa; Anderson, Rob; Araya, Ricardo; Lewis, Glyn; Millings, Abigail; Montgomery, Alan A

2012-01-01

Objective To compare the effectiveness of classroom based cognitive behavioural therapy with attention control and usual school provision for adolescents at high risk of depression. Design Three arm parallel cluster randomised controlled trial. Setting Eight UK secondary schools. Participants Adolescents (n=5030) aged 12-16 years in school year groups 8-11. Year groups were randomly assigned on a 1:1:1 ratio to cognitive behavioural therapy, attention control, or usual school provision. Allocation was balanced by school, year, number of students and classes, frequency of lessons, and timetabling. Participants were not blinded to treatment allocation. Interventions Cognitive behavioural therapy, attention control, and usual school provision provided in classes to all eligible participants. Main outcome measures Outcomes were collected by self completed questionnaire administered by researchers. The primary outcome was symptoms of depression assessed at 12 months by the short mood and feelings questionnaire among those identified at baseline as being at high risk of depression. Secondary outcomes included negative thinking, self worth, and anxiety. Analyses were undertaken on an intention to treat basis and accounted for the clustered nature of the design. Results 1064 (21.2%) adolescents were identified at high risk of depression: 392 in the classroom based cognitive behavioural therapy arm, 374 in the attention control arm, and 298 in the usual school provision arm. At 12 months adjusted mean scores on the short mood and feelings questionnaire did not differ for cognitive behavioural therapy versus attention control (−0.63, 95% confidence interval −1.85 to 0.58, P=0.41) or for cognitive behavioural therapy versus usual school provision (0.97, −0.20 to 2.15, P=0.12). Conclusion In adolescents with depressive symptoms, outcomes were similar for attention control, usual school provision, and cognitive behavioural therapy. Classroom based cognitive behavioural therapy programmes may result in increased self awareness and reporting of depressive symptoms but should not be undertaken without further evaluation and research. Trial registration Current Controlled Trials ISRCTN19083628. PMID:23043090

Correcting for multiple-testing in multi-arm trials: is it necessary and is it done?

PubMed

Wason, James M S; Stecher, Lynne; Mander, Adrian P

2014-09-17

Multi-arm trials enable the evaluation of multiple treatments within a single trial. They provide a way of substantially increasing the efficiency of the clinical development process. However, since multi-arm trials test multiple hypotheses, some regulators require that a statistical correction be made to control the chance of making a type-1 error (false-positive). Several conflicting viewpoints are expressed in the literature regarding the circumstances in which a multiple-testing correction should be used. In this article we discuss these conflicting viewpoints and review the frequency with which correction methods are currently used in practice. We identified all multi-arm clinical trials published in 2012 by four major medical journals. Summary data on several aspects of the trial design were extracted, including whether the trial was exploratory or confirmatory, whether a multiple-testing correction was applied and, if one was used, what type it was. We found that almost half (49%) of published multi-arm trials report using a multiple-testing correction. The percentage that corrected was higher for trials in which the experimental arms included multiple doses or regimens of the same treatments (67%). The percentage that corrected was higher in exploratory than confirmatory trials, although this is explained by a greater proportion of exploratory trials testing multiple doses and regimens of the same treatment. A sizeable proportion of published multi-arm trials do not correct for multiple-testing. Clearer guidance about whether multiple-testing correction is needed for multi-arm trials that test separate treatments against a common control group is required.

Treating neurocysticercosis medically: a systematic review of randomized, controlled trials.

PubMed

Salinas, R; Counsell, C; Prasad, K; Gelband, H; Garner, P

1999-11-01

To summarize the evidence from randomized controlled trials on the effects of cysticidal therapy used for treating human cysticercosis. Published and unpublished studies in any language identified through MEDLINE (1966 - June 1999) specialized databases, abstracts, proceedings and contact with experts were analysed. Those which compared, using randomized or quasi-randomized methods, any cysticidal drug with placebo or symptomatic therapy were entered in the study. Data were extracted independently by two reviewers and trial quality assessed. Meta-analysis using fixed effects models calculated provided there was no significant heterogeneity, expressed as relative risk. Four trials met the inclusion criteria, treating intraparenchymatous neurocysticercosis with either albendazole or praziquantel compared to placebo or no treatment. In the two trials reporting clinical outcomes, treatment was not associated with a reduction in the risk of seizures, although numbers were small (RR 0.95, 95% CI 0.59-1.51). Four trials reported radiological outcomes, and cysticidal treatment was associated with a lower risk of cyst persistence of scans taken within six months of start of treatment (RR 0.83, 95% CI 0.70-0.99). Subsidiary analysis assuming different outcomes in patients lost to follow-up did not alter the findings of the main analysis. There is insufficient evidence to determine whether cysticidal therapy is of any clinical benefit to patients with neurocysticercosis. The review does not exclude the possibility that more patients remain seizure-free when treated with cysticidal drugs. Further testing through placebo-controlled trials is required.

The effectiveness of non-surgical interventions in the treatment of Charcot foot.

PubMed

Smith, Caroline; Kumar, Saravana; Causby, Ryan

2007-12-01

Background  Charcot neuropathic osteoarthropathy is commonly known as 'Charcot foot'. It is a serious foot complication of diabetes mellitus that can frequently lead to foot ulceration, gangrene, hospital admission and foot amputation. A multidisciplinary approach to the management of Charcot foot is taken involving medical and allied health professionals. The management approach may also differ between different countries. To date, there is no systematic review of the literature undertaken to identify the clinical effectiveness of non-operative interventions in the treatment of acute Charcot foot. Objective  The objective of this review was to identify the effectiveness of non-surgical interventions with reducing lesions, ulceration, the rate of surgical intervention, reducing hospital admissions and improve the quality of life of subjects with Charcot foot. Search strategy  A comprehensive search strategy was undertaken on databases available from University of South Australia from their inception to November 2006. Selection criteria  Randomised controlled trials or clinical controlled trials were primarily sought. Critical appraisal of study quality and data extraction was undertaken using Joanna Briggs Institute instruments. Review Manager software was used to calculate comparative statistics. Results  This review identified 11 trials and five trials were included in the review. Three trials involved the use of bisphosphonate, a pharmacological agent. Two experimental treatments were also included, evaluating palliative radiology and magnetic fields. No trials were found using immobilisation and off-loading interventions for acute Charcot foot. The overall methodological quality score of the five studies was moderate. Owing to heterogeneous data, meta-analysis could not be performed. The trials did not report on reducing lesions, ulceration, rate of surgical intervention, hospital admissions and the quality of life of subjects with Charcot foot. The trials evaluating bisphosphonates reported greater reduction in foot temperature and disease activity for intervention subjects compared with controls. Another outcome of this review indicated additional beneficial effects of bisphosphonates in reducing pain and discomfort. The trial evaluating palliative radiotherapy found no difference between groups on any outcome. A significant reduction in the amount of deformity and reduced healing time to consolidation was found after treatment in the group receiving magnetic therapy treatment. Discussion  There is a lack of clinical trials evaluating the effectiveness of non-operative interventions for the management of Charcot foot (immobilisation, removable cast walkers, advice/dispensing of footwear and prescribing of orthotics). Bisphosphonates may be useful adjuncts to standard management of Charcot foot by improved healing demonstrated by a reduction in disease activity indicated by skin temperature and bone destruction. Magnetic therapy may reduce deformity, joint destruction and improve mobility. Conclusion  There is a lack of evidence supporting the use of pharmacological or non-surgical interventions with reducing lesions, ulceration, rate of surgical intervention, hospital admissions and improving the quality of life of subjects with Charcot foot. Bisphosphonates may improve the healing of Charcot foot by reducing skin temperature and disease activity of Charcot foot, when applied in addition to standard interventions to control the position and shape of the foot.

Gene therapy for haemophilia.

PubMed

Sharma, Akshay; Easow Mathew, Manu; Sriganesh, Vasumathi; Neely, Jessica A; Kalipatnapu, Sasank

2014-11-14

Haemophilia is a genetic disorder which is characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 06 November 2014. Eligible trials included randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. No trials of gene therapy for haemophilia were found. No trials of gene therapy for haemophilia were identified. No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the effects of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

The Use of Mixed Methods in Randomized Control Trials

ERIC Educational Resources Information Center

White, Howard

2013-01-01

Evaluations should be issues driven, not methods driven. The starting point should be priority programs to be evaluated or policies to be tested. From this starting point, a list of evaluation questions is identified. For each evaluation question, the task is to identify the best available method for answering that question. Hence it is likely…

Efficacy of electroacupuncture for symptoms of menopausal transition: study protocol for a randomized controlled trial.

PubMed

Liu, Zhishun; Wang, Yang; Xu, Huanfang; Wu, Jiani; He, Liyun; Jiang, John Yi; Yan, Shiyan; Du, Ruosang; Liu, Baoyan

2014-06-21

Previous studies have shown that acupuncture can alleviate postmenopausal symptoms, such as hot flashes, but few studies have assessed symptoms during the menopausal transition (MT) period. Thus, the effect of acupuncture upon MT symptoms is unclear. We designed a large-scale trial aimed at evaluating the efficacy of electroacupuncture for MT symptoms compared with sham electroacupuncture and at observing the safety of electroacupuncture. In this multicenter randomized controlled trial, 360 women will be randomized to either an electroacupuncture group or a sham electroacupuncture group. During the 8-week-long treatment, a menopause rating scale, average 24-hour hot flash score, Menopause-Specific Quality of Life Questionnaire score, and level of female hormones will be observed. Follow-ups at the 20th and 32nd week will be made. Though there is no completely inert placebo acupuncture and blinding is difficult in acupuncture trials, the placebo effect of EA can still be partially excluded in this study. For the placebo control, we use non-points and a tailor-made sham needle. This needle is different from a retractable needle, which is usually used for sham acupuncture. The needle in this trial is more simply constructed and more acceptable to Chinese people. We expect to evaluate the efficacy of electroacupuncture for MT symptoms and clarify its effect on these symptoms. ClinicalTrials.gov Identifier: NCT01849172 (Date of registration: 05/05/2013).

Radiation Therapy Intensification for Solid Tumors: A Systematic Review of Randomized Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamoah, Kosj; Showalter, Timothy N.; Ohri, Nitin, E-mail: ohri.nitin@gmail.com

Purpose: To systematically review the outcomes of randomized trials testing radiation therapy (RT) intensification, including both dose escalation and/or the use of altered fractionation, as a strategy to improve disease control for a number of malignancies. Methods and Materials: We performed a literature search to identify randomized trials testing RT intensification for cancers of the central nervous system, head and neck, breast, lung, esophagus, rectum, and prostate. Findings were described qualitatively. Where adequate data were available, pooled estimates for the effect of RT intensification on local control (LC) or overall survival (OS) were obtained using the inverse variance method. Results: Inmore » primary central nervous system tumors, esophageal cancer, and rectal cancer, randomized trials have not demonstrated that RT intensification improves clinical outcomes. In breast cancer and prostate cancer, dose escalation has been shown to improve LC or biochemical disease control but not OS. Radiation therapy intensification may improve LC and OS in head and neck and lung cancers, but these benefits have generally been limited to studies that did not incorporate concurrent chemotherapy. Conclusions: In randomized trials, the benefits of RT intensification have largely been restricted to trials in which concurrent chemotherapy was not used. Novel strategies to optimize the incorporation of RT in the multimodality treatment of solid tumors should be explored.« less

Estimating economic thresholds for site-specific weed control using manual weed counts and sensor technology: an example based on three winter wheat trials.

PubMed

Keller, Martina; Gutjahr, Christoph; Möhring, Jens; Weis, Martin; Sökefeld, Markus; Gerhards, Roland

2014-02-01

Precision experimental design uses the natural heterogeneity of agricultural fields and combines sensor technology with linear mixed models to estimate the effect of weeds, soil properties and herbicide on yield. These estimates can be used to derive economic thresholds. Three field trials are presented using the precision experimental design in winter wheat. Weed densities were determined by manual sampling and bi-spectral cameras, yield and soil properties were mapped. Galium aparine, other broad-leaved weeds and Alopecurus myosuroides reduced yield by 17.5, 1.2 and 12.4 kg ha(-1) plant(-1)  m(2) in one trial. The determined thresholds for site-specific weed control with independently applied herbicides were 4, 48 and 12 plants m(-2), respectively. Spring drought reduced yield effects of weeds considerably in one trial, since water became yield limiting. A negative herbicide effect on the crop was negligible, except in one trial, in which the herbicide mixture tended to reduce yield by 0.6 t ha(-1). Bi-spectral cameras for weed counting were of limited use and still need improvement. Nevertheless, large weed patches were correctly identified. The current paper presents a new approach to conducting field trials and deriving decision rules for weed control in farmers' fields. © 2013 Society of Chemical Industry.

MIDAS: a practical Bayesian design for platform trials with molecularly targeted agents.

PubMed

Yuan, Ying; Guo, Beibei; Munsell, Mark; Lu, Karen; Jazaeri, Amir

2016-09-30

Recent success of immunotherapy and other targeted therapies in cancer treatment has led to an unprecedented surge in the number of novel therapeutic agents that need to be evaluated in clinical trials. Traditional phase II clinical trial designs were developed for evaluating one candidate treatment at a time and thus not efficient for this task. We propose a Bayesian phase II platform design, the multi-candidate iterative design with adaptive selection (MIDAS), which allows investigators to continuously screen a large number of candidate agents in an efficient and seamless fashion. MIDAS consists of one control arm, which contains a standard therapy as the control, and several experimental arms, which contain the experimental agents. Patients are adaptively randomized to the control and experimental agents based on their estimated efficacy. During the trial, we adaptively drop inefficacious or overly toxic agents and 'graduate' the promising agents from the trial to the next stage of development. Whenever an experimental agent graduates or is dropped, the corresponding arm opens immediately for testing the next available new agent. Simulation studies show that MIDAS substantially outperforms the conventional approach. The proposed design yields a significantly higher probability for identifying the promising agents and dropping the futile agents. In addition, MIDAS requires only one master protocol, which streamlines trial conduct and substantially decreases the overhead burden. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

MIDAS: A Practical Bayesian Design for Platform Trials with Molecularly Targeted Agents

PubMed Central

Yuan, Ying; Guo, Beibei; Munsell, Mark; Lu, Karen; Jazaeri, Amir

2016-01-01

Recent success of immunotherapy and other targeted therapies in cancer treatment has led to an unprecedented surge in the number of novel therapeutic agents that need to be evaluated in clinical trials. Traditional phase II clinical trial designs were developed for evaluating one candidate treatment at a time, and thus not efficient for this task. We propose a Bayesian phase II platform design, the Multi-candidate Iterative Design with Adaptive Selection (MIDAS), which allows investigators to continuously screen a large number of candidate agents in an efficient and seamless fashion. MIDAS consists of one control arm, which contains a standard therapy as the control, and several experimental arms, which contain the experimental agents. Patients are adaptively randomized to the control and experimental agents based on their estimated efficacy. During the trial, we adaptively drop inefficacious or overly toxic agents and “graduate” the promising agents from the trial to the next stage of development. Whenever an experimental agent graduates or is dropped, the corresponding arm opens immediately for testing the next available new agent. Simulation studies show that MIDAS substantially outperforms the conventional approach. The proposed design yields a significantly higher probability for identifying the promising agents and dropping the futile agents. In addition, MIDAS requires only one master protocol, which streamlines trial conduct and substantially decreases the overhead burden. PMID:27112322

Meta-Analysis: Risk of Tics Associated With Psychostimulant Use in Randomized, Placebo-Controlled Trials.

PubMed

Cohen, Stephanie C; Mulqueen, Jilian M; Ferracioli-Oda, Eduardo; Stuckelman, Zachary D; Coughlin, Catherine G; Leckman, James F; Bloch, Michael H

2015-09-01

Clinical practice currently restricts the use of psychostimulant medications in children with tics or a family history of tics for fear that tics will develop or worsen as a side effect of treatment. Our goal was to conduct a meta-analysis to examine the risk of new onset or worsening of tics as an adverse event of psychostimulants in randomized, placebo-controlled trials. We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). We used a fixed effects meta-analysis with risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dose, duration of treatment, recorder of side effect data, trial design, and mean age of participants on the measured risk of tics. We identified 22 studies involving 2,385 children with ADHD for inclusion in our meta-analysis. New onset tics or worsening of tic symptoms were commonly reported in the psychostimulant (event rate = 5.7%, 95% CI = 3.7%-8.6%) and placebo groups (event rate = 6.5%, 95% CI = 4.4%-9.5%). The risk of new onset or worsening of tics associated with psychostimulant treatment was similar to that observed with placebo (risk ratio = 0.99, 95% CI = 0.78-1.27, z = -0.05, p = .962). Type of psychostimulant, dose, duration of treatment, recorder, and participant age did not affect risk of new onset or worsening of tics. Crossover studies were associated with a significantly greater measured risk of tics with psychostimulant use compared to parallel group trials. Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant use, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Enhancing first-time parents' self-efficacy: A systematic review and meta-analysis of universal parent education interventions' efficacy.

PubMed

Liyana Amin, Nur Arina; Tam, Wilson W S; Shorey, Shefaly

2018-06-01

Poor adjustment during early parenthood often leads to low feelings of parental self-efficacy, which influences parents' behaviours towards their infants. The long-term consequences on infant development warrant the need for more attention on the efficacy of universal parent education interventions to empower parents and enhance their self-efficacy. To synthesise available evidence and explore the efficacy of universal parent education interventions on the parental self-efficacy of first-time parents. A systematic review and meta-analysis of randomised controlled trials. A literature search of 10 databases was conducted to identify randomised controlled trials from each database's point of inception to November 2016. Based on the inclusion criteria, 24,062 articles were screened for their titles and abstracts. Two hundred and eighty articles were identified for full-text screening. Risks of bias posed by the selected articles were assessed using Cochrane's Risk of Bias instrument. Meta-analyses were conducted using RevMan 5.3. The overall intervention effect was evaluated using z tests at p < 0.05, while I 2 and Cochran Q tests were used to measure heterogeneity. Ten randomised controlled trials were selected; eight trials were combined in meta-analyses and two trials were synthesised narratively. A meta-analysis revealed that universal parent education interventions significantly enhanced parental self-efficacy (p < 0.001) among first-time parents and these effects were also maintained over time (p < 0.001). The extent of improvement in parental self-efficacy was affected by the duration of the interventions. This review provides sufficient evidence to support the use of universal interventions to enhance new parents' self-efficacy. While intervention effects were sustained at the two-month follow-up, further research using randomised controlled trials and longitudinal studies are needed to determine long-term effects. The findings serve as an impetus for hospitals and healthcare professionals to integrate universal interventions in perinatal care to guide first-time parents' transition into parenthood. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Surrogate endpoints for overall survival in metastatic melanoma: a meta-analysis of randomised controlled trials

PubMed Central

Flaherty, Keith T; Hennig, Michael; Lee, Sandra J; Ascierto, Paolo A; Dummer, Reinhard; Eggermont, Alexander M M; Hauschild, Axel; Kefford, Richard; Kirkwood, John M; Long, Georgina V; Lorigan, Paul; Mackensen, Andreas; McArthur, Grant; O'Day, Steven; Patel, Poulam M; Robert, Caroline; Schadendorf, Dirk

2015-01-01

Summary Background Recent phase 3 trials have shown an overall survival benefit in metastatic melanoma. We aimed to assess whether progression-free survival (PFS) could be regarded as a reliable surrogate for overall survival through a meta-analysis of randomised trials. Methods We systematically reviewed randomised trials comparing treatment regimens in metastatic melanoma that included dacarbazine as the control arm, and which reported both PFS and overall survival with a standard hazard ratio (HR). We correlated HRs for overall survival and PFS, weighted by sample size or by precision of the HR estimate, assuming fixed and random effects. We did sensitivity analyses according to presence of crossover, trial size, and dacarbazine dose. Findings After screening 1649 reports and meeting abstracts published before Sept 8, 2013, we identified 12 eligible randomised trials that enrolled 4416 patients with metastatic melanoma. Irrespective of weighting strategy, we noted a strong correlation between the treatment effects for PFS and overall survival, which seemed independent of treatment type. Pearson correlation coefficients were 0.71 (95% CI 0.29–0.90) with a random-effects assumption, 0.85 (0.59–0.95) with a fixed-effects assumption, and 0.89 (0.68–0.97) with sample-size weighting. For nine trials without crossover, the correlation coefficient was 0.96 (0.81–0.99), which decreased to 0.93 (0.74–0.98) when two additional trials with less than 50% crossover were included. Inclusion of mature follow-up data after at least 50% crossover (in vemurafenib and dabrafenib phase 3 trials) weakened the PFS to overall survival correlation (0.55, 0.03–0.84). Inclusion of trials with no or little crossover with the random-effects assumption yielded a conservative statement of the PFS to overall survival correlation of 0.85 (0.51–0.96). Interpretation PFS can be regarded as a robust surrogate for overall survival in dacarbazine-controlled randomised trials of metastatic melanoma; we postulate that this association will hold as treatment standards evolve and are adopted as the control arm in future trials. Funding None. PMID:24485879

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.

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.

Planned early delivery versus expectant management for monoamniotic twins.

PubMed

Shub, Alexis; Walker, Susan P

2015-04-23

Monoamniotic twin pregnancies are formed when a single egg is fertilised and the resulting inner cell mass splits to form twins sharing the same amniotic sac. This condition is rare and affects about one in 10,000 pregnancies overall. Monoamniotic twin pregnancies are susceptible to complications including cord entanglement, increased congenital anomalies, intrauterine growth restriction, twin-to-twin transfusion syndrome and increased perinatal mortality. All twin pregnancies also carry additional maternal risks including pre-eclampsia, anaemia, antepartum haemorrhage, postpartum haemorrhage and operative delivery.The optimal timing for the delivery of monoamniotic twins is not known. The options include 'planned early delivery' between 32 and 34 weeks, or alternatively awaiting spontaneous labour at least up until the usual time of planned delivery for other monochorionic twins (approximately 36 to 38 weeks' gestation), unless there is a specific indication for earlier delivery. To assess whether routine early delivery in monoamniotic twin pregnancies improves fetal, neonatal or maternal outcomes compared with 'expectant management'. Expectant management means awaiting spontaneous labour at least up until the usual time of planned delivery for other monochorionic twins (approximately 36 to 38 weeks' gestation in many centres), unless a specific indication for delivery occurs in the meantime, e.g. for non-reassuring antenatal testing. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2015). Published and unpublished randomised controlled trials (including cluster-randomised trials) comparing outcomes for women and infants who were randomised to planned early delivery of a monoamniotic twin pregnancy with outcomes for women and infants who were randomised to either planned term delivery or expectant management. However, we did not identify any trials for inclusion in this review.Quasi-randomised controlled trials, trials published in abstract form only, and trials using a cross-over design are not eligible for inclusion in this review. No trials were identified by the search strategy. No trials were identified by the search strategy. Monoamniotic twins are rare, and there is insufficient randomised controlled evidence on which to draw strong conclusions about the best management. In their absence, we can refer to historical case series and expert consensus. Management plans should take into consideration the availability of high-quality neonatal care if early delivery is chosen. Women and their families should be involved in the decision making about these high-risk pregnancies.Ongoing, multicentre audits of maternal and perinatal outcomes for monoamniotic twins are needed in order to inform families and clinicians about up-to-date perinatal outcomes with contemporary obstetric practice. Research should consider the social and economic implications of planned interventions, as well as the perinatal outcomes.

Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics.

PubMed

Selle, V; Schalkwijk, S; Vázquez, G H; Baldessarini, R J

2014-03-01

Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants. We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants, second-generation antipsychotics, or lithium for acute major depressive episodes in patients diagnosed with type I or II bipolar disorder and applied random-effects meta-analysis to evaluate their efficacy, comparing outcomes based on standardized mean drug-placebo differences (SMD) in improvement, relative response rates (RR), and number-needed-to-treat (NNT). We identified 24 trials of 10 treatments (lasting 7.5 weeks, with ≥ 50 collaborating sites/trial) that met eligibility criteria: lamotrigine (5 trials), quetiapine (5), valproate (4), 2 each for aripiprazole, olanzapine, ziprasidone, and 1 each for carbamazepine, lithium, lurasidone, and olanzapine-fluoxetine. Overall, pooled drug-over-placebo responder-rate superiority (RR) was moderate (29% [CI: 19-40%]), and NNT was 8.2 (CI: 6.4-11). By SMD, apparent efficacy ranked: olanzapine + fluoxetine ≥ valproate > quetiapine > lurasidone > olanzapine, aripiprazole, and carbamazepine; ziprasidone was ineffective, and lithium remains inadequately studied. Notably, drugs were superior to placebo in only 11/24 trials (5/5 with quetiapine, 2/4 with valproate), and only lamotrigine, quetiapine and valproate had > 2 trials. Treatment-associated mania-like reactions were uncommon (drugs: 3.7%; placebo: 4.7%). Controlled trials of non-antidepressant treatments for bipolar depression remain scarce, but findings with olanzapine-fluoxetine, lurasidone, quetiapine, and perhaps carbamazepine and valproate were encouraging; lithium requires adequate testing. © Georg Thieme Verlag KG Stuttgart · New York.

Cluster Randomised Trials in Cochrane Reviews: Evaluation of Methodological and Reporting Practice.

PubMed

Richardson, Marty; Garner, Paul; Donegan, Sarah

2016-01-01

Systematic reviews can include cluster-randomised controlled trials (C-RCTs), which require different analysis compared with standard individual-randomised controlled trials. However, it is not known whether review authors follow the methodological and reporting guidance when including these trials. The aim of this study was to assess the methodological and reporting practice of Cochrane reviews that included C-RCTs against criteria developed from existing guidance. Criteria were developed, based on methodological literature and personal experience supervising review production and quality. Criteria were grouped into four themes: identifying, reporting, assessing risk of bias, and analysing C-RCTs. The Cochrane Database of Systematic Reviews was searched (2nd December 2013), and the 50 most recent reviews that included C-RCTs were retrieved. Each review was then assessed using the criteria. The 50 reviews we identified were published by 26 Cochrane Review Groups between June 2013 and November 2013. For identifying C-RCTs, only 56% identified that C-RCTs were eligible for inclusion in the review in the eligibility criteria. For reporting C-RCTs, only eight (24%) of the 33 reviews reported the method of cluster adjustment for their included C-RCTs. For assessing risk of bias, only one review assessed all five C-RCT-specific risk-of-bias criteria. For analysing C-RCTs, of the 27 reviews that presented unadjusted data, only nine (33%) provided a warning that confidence intervals may be artificially narrow. Of the 34 reviews that reported data from unadjusted C-RCTs, only 13 (38%) excluded the unadjusted results from the meta-analyses. The methodological and reporting practices in Cochrane reviews incorporating C-RCTs could be greatly improved, particularly with regard to analyses. Criteria developed as part of the current study could be used by review authors or editors to identify errors and improve the quality of published systematic reviews incorporating C-RCTs.

Do workplace physical activity interventions improve mental health outcomes?

PubMed

Chu, A H Y; Koh, D; Moy, F M; Müller-Riemenschneider, F

2014-06-01

Mental health is an important issue in the working population. Interventions to improve mental health have included physical activity. To review evidence for the effectiveness of workplace physical activity interventions on mental health outcomes. A literature search was conducted for studies published between 1990 and August 2013. Inclusion criteria were physical activity trials, working populations and mental health outcomes. Study quality was assessed using the Jadad scale. Of 3684 unique articles identified, 17 met all selection criteria, including 13 randomized controlled trials, 2 comparison trials and 2 controlled trials. Studies were grouped into two key intervention areas: physical activity and yoga exercise. Of eight high-quality trials, two provided strong evidence for a reduction in anxiety, one reported moderate evidence for an improvement in depression symptoms and one provided limited evidence on relieving stress. The remaining trials did not provide evidence on improved mental well-being. Workplace physical activity and yoga programmes are associated with a significant reduction in depressive symptoms and anxiety, respectively. Their impact on stress relief is less conclusive. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

A review of escitalopram and citalopram in child and adolescent depression.

PubMed

Carandang, Carlo; Jabbal, Rekha; Macbride, Angela; Elbe, Dean

2011-11-01

To review the basic pharmacology and published literature regarding escitalopram and citalopram in child and adolescent depression. A LITERATURE REVIEW WAS CONDUCTED USING THE SEARCH TERMS: 'escitalopram', 'citalopram', 'depression', 'randomized controlled trial', 'open label trial' and limits set to: Human trials, English Language and All Child (Age 0-18). Additional articles were identified from reference information and poster presentation data. Three prospective, randomized controlled trials (RCT) were found for escitalopram in pediatric depression, and two RCTs were found for citalopram. One RCT each for escitalopram and citalopram showed superiority over placebo on the primary out come measure. Adverse effects in escitalopram and citalopram trials were generally mild to moderate. Suicidality was not assessed systematically in all RCTs reviewed, but did not appear to be elevated over placebo in escitalopram RCTs. One trial reported numerically higher suicide related events for citalopram compared to placebo (14 vs. 5, p=0.06). At present, escitalopram and citalopram should be considered a second-line option for adolescent depression. The US Food and Drug Administration approval of escitalopram for treatment of adolescent depression was based on a single positive RCT. This is less evidence than typically required for approval of a drug for a new indication.

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

Evidence for the use of parenteral nutrition in the pediatric intensive care unit.

PubMed

Fivez, Tom; Kerklaan, Dorian; Mesotten, Dieter; Verbruggen, Sascha; Joosten, Koen; Van den Berghe, Greet

2017-02-01

During hospitalization in a pediatric intensive care unit (PICU), critically ill children are fed artificially. Administered via the preferred enteral route, caloric targets are often not reached. Hence, parenteral nutrition is given to this patient population. In this review we analyzed the available evidence from randomized controlled trials (RCTs) that supports the use of parenteral nutrition in children during critical illness. A search strategy in Ovid MEDLINE and Ovid EMBASE was created and trial registries were screened to identify the relevant RCTs. Studies were included if they were randomized controlled trials, involved pediatric patients admitted to PICU, and compared different dosing/compositions of parenteral nutrition. Descriptive studies and reviews were excluded. Of the 584 articles identified by the search strategy, only 114 articles were retained after title screening. Further abstract and full text screening identified 6 small RCTs that compared two dosing/composition strategies of parenteral nutrition. These trials reported differences in surrogate endpoints without an effect on hard clinical endpoints. The RCTs observed improvements in these surrogate endpoints with the use of more calories or when parenteral glutamine or fish oil was added. The few RCTs suggest that surrogate endpoints can be affected by providing parenteral nutrition to critically ill children, but the studies were not statistically powered to draw meaningful clinical conclusions. Large RCTs with clinically relevant outcome measures are urgently needed to support the current nutritional guidelines that advise the use of parenteral nutrition in the PICU. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Complementary and alternative medicine for rheumatic diseases: A systematic review of randomized controlled trials.

PubMed

Phang, Jie Kie; Kwan, Yu Heng; Goh, Hendra; Tan, Victoria Ie Ching; Thumboo, Julian; Østbye, Truls; Fong, Warren

2018-04-01

To summarize all good quality randomized controlled trials (RCTs) using complementary and alternative medicine (CAM) interventions in patients with rheumatic diseases. A systematic literature review guided by the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) was performed. We excluded non-English language articles and abstract-only publications. Due to the large number of RCTs identified, we only include "good quality" RCTs with Jadad score of five. We identified 60 good quality RCTs using CAM as intervention for patients with rheumatic diseases: acupuncture (9), Ayurvedic treatment (3), homeopathic treatment (3), electricity (2), natural products (31), megavitamin therapies (8), chiropractic or osteopathic manipulation (3), and energy healing therapy (1). The studies do not seem to suggest a particular type of CAM is effective for all types for rheumatic diseases. However, some CAM interventions appear to be more effective for certain types of rheumatic diseases. Acupuncture appears to be beneficial for osteoarthritis but not rheumatoid arthritis. For the other therapeutic modalities, the evidence base either contains too few trials or contains trials with contradictory findings which preclude any definitive summary. There were only minor adverse reactions observed for CAM interventions presented. We identified 60 good quality RCTs which were heterogenous in terms of interventions, disease, measures used to assess outcomes, and efficacy of CAM interventions. Evidence indicates that some CAM therapies may be useful for rheumatic diseases, such as acupuncture for osteoarthritis. Further research with larger sample size is required for more conclusive evidence regarding efficacy of CAM interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Face washing promotion for preventing active trachoma

PubMed Central

Ejere, Henry OD; Alhassan, Mahmoud B; Rabiu, Mansur

2015-01-01

Background Trachoma remains a major cause of avoidable blindness among underprivileged populations in many developing countries. It is estimated that about 146 million people have active trachoma and nearly six million people are blind due to complications associated with repeat infections. Objectives The objective of this review was to assess the effects of face washing promotion for the prevention of active trachoma in endemic communities. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015), PubMed (January 1948 to January 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to January 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (accessed 10 January 2014), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (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 26 January 2015. To identify further relevant trials we checked the reference lists of the included trials. Also, we used the Science Citation Index to search for references to publications that cited the trials included in the review. We contacted investigators and experts in the field to identify additional trials. Selection criteria We included randomized controlled trials (RCTs) or quasi-RCTs that compared face washing with no treatment or face washing combined with antibiotics against antibiotics alone. Trial participants were residents of endemic trachoma communities. Data collection and analysis Two review authors independently extracted data and assessed trial quality. We contacted trial authors for additional information when needed. Two trials met our inclusion criteria; but we did not conduct meta-analysis due to methodological heterogeneity. Main results We included two cluster-RCTs, which provided data from 2447 participants. Both trials were conducted in areas endemic to trachoma: Northern Australia and Tanzania. The follow-up period was three months in one trial and 12 months in the other; both trials had about 90% participant follow-up at final visit. Overall the quality of the evidence is uncertain due to the trials not reporting many design methods and the differences in outcomes reported between trials. Face washing combined with topical tetracycline was compared with topical tetracycline alone in three pairs of villages in one trial. The trial found that face washing combined with topical tetracycline reduced ’severe’ active trachoma compared with topical tetracycline alone at 12 months (adjusted odds ratio (OR) 0.62, 95% confidence interval (CI) 0.40 to 0.97); however, the trial did not find any important difference between the intervention and control villages in reducing other types of active trachoma (adjusted OR 0.81, 95% CI 0.42 to 1.59). Intervention villages had a higher prevalence of clean faces than the control villages among children with severe trachoma (adjusted OR 0.35, 95% CI 0.21 to 0.59) and any trachoma (adjusted OR 0.58, 95% CI 0.47 to 0.72) at 12 months follow-up. The second trial compared eye washing to no treatment or to topical tetracycline alone or to a combination of eye washing and tetracycline drops in children with follicular trachoma. At three months, the trial found no evidence of benefit of eye washing alone or in combination with tetracycline eye drops in reducing follicular trachoma amongst children with follicular trachoma (risk ratio (RR) 1.03, 95% CI 0.96 to 1.11; one trial, 1143 participants). Authors’ conclusions There is evidence from one trial that face washing combined with topical tetracycline may be effective in reducing severe active trachoma and in increasing the prevalence of clean faces at one year follow-up. Current evidence is inconclusive as to the effectiveness of face washing alone or in combination with topical tetracycline in reducing active or severe trachoma. PMID:25697765

Glutamine supplementation to prevent morbidity and mortality in preterm infants.

PubMed

Moe-Byrne, Thirimon; Brown, Jennifer V E; McGuire, William

2016-01-12

Glutamine is a conditionally essential amino acid. Endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Evidence exists that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may also benefit preterm infants. To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 12), MEDLINE, EMBASE and Maternity and Infant Care (to December 2015), conference proceedings and previous reviews. Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm infants at any time from birth to discharge from hospital. We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. We synthesised data using a fixed-effect model and reported typical relative risk, typical risk difference and weighted mean difference. We identified 12 randomised controlled trials in which a total of 2877 preterm infants participated. Six trials assessed enteral glutamine supplementation and six trials assessed parenteral glutamine supplementation. The trials were generally of good methodological quality. Meta-analysis did not find an effect of glutamine supplementation on mortality (typical relative risk 0.97, 95% confidence interval 0.80 to 1.17; risk difference 0.00, 95% confidence interval -0.03 to 0.02) or major neonatal morbidities including the incidence of invasive infection or necrotising enterocolitis. Three trials that assessed neurodevelopmental outcomes in children aged 18 to 24 months and beyond did not find any effects. The available trial data do not provide evidence that glutamine supplementation confers important benefits for preterm infants.

Glutamine supplementation to prevent morbidity and mortality in preterm infants.

PubMed

Moe-Byrne, Thirimon; Brown, Jennifer V E; McGuire, William

2016-04-18

Glutamine is a conditionally essential amino acid. Endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Evidence exists that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may also benefit preterm infants. To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 12), MEDLINE, EMBASE and Maternity and Infant Care (to December 2015), conference proceedings and previous reviews. Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm infants at any time from birth to discharge from hospital. We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. We synthesised data using a fixed-effect model and reported typical relative risk, typical risk difference and weighted mean difference. We identified 12 randomised controlled trials in which a total of 2877 preterm infants participated. Six trials assessed enteral glutamine supplementation and six trials assessed parenteral glutamine supplementation. The trials were generally of good methodological quality. Meta-analysis did not find an effect of glutamine supplementation on mortality (typical relative risk 0.97, 95% confidence interval 0.80 to 1.17; risk difference 0.00, 95% confidence interval -0.03 to 0.02) or major neonatal morbidities including the incidence of invasive infection or necrotising enterocolitis. Three trials that assessed neurodevelopmental outcomes in children aged 18 to 24 months and beyond did not find any effects. The available trial data do not provide evidence that glutamine supplementation confers important benefits for preterm infants.

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.

Community-Based Intervention to Improve Cardiometabolic Targets in Patients With Stroke: A Randomized Controlled Trial.

PubMed

Olaiya, Muideen T; Cadilhac, Dominique A; Kim, Joosup; Nelson, Mark R; Srikanth, Velandai K; Gerraty, Richard P; Bladin, Christopher F; Fitzgerald, Sharyn M; Phan, Thanh; Frayne, Judith; Thrift, Amanda G

2017-09-01

Many guidelines for secondary prevention of stroke focus on controlling cardiometabolic risk factors. We investigated the effectiveness of a management program for attaining cardiometabolic targets in survivors of stroke/transient ischemic attack. Randomized controlled trial of survivors of stroke/transient ischemic attack aged ≥18 years. General practices were randomized to usual care (control) or an intervention comprising specialist review of care plans and nurse education in addition to usual care. The outcome is attainment of pre-defined cardiometabolic targets based on Australian guidelines. Multivariable regression was undertaken to determine efficacy and identify factors associated with attaining targets. Overall, 283 subjects were randomized to the intervention and 280 to controls. Although we found no between-group difference in overall cardiometabolic targets achieved at 12 months, the intervention group more often achieved control of low-density lipoprotein cholesterol (odds ratio, 1.97; 95% confidence interval, 1.18-3.29) than controls. At 24 months, no between-group differences were observed. Medication adherence was ≥80% at follow-up, but uptake of lifestyle/behavioral habits was poor. Older age, being male, being married/living with partner, and having greater functional ability or a history of diabetes mellitus were associated with attaining targets. The intervention in this largely negative trial only had a detectable effect on attaining target for lipids but not for other factors at 12 months or any factor at 24 months. This limited effect may be attributable to inadequate uptake of behavioral/lifestyle interventions, highlighting the need for new or better approaches to achieve meaningful behavioral change. URL: http://www.clinicaltrials.gov. Unique identifier: ACTRN12608000166370. © 2017 American Heart Association, Inc.

Does Altered Uric Acid Metabolism Contribute to Diabetic Kidney Disease Pathophysiology?

PubMed

Gul, Ambreen; Zager, Philip

2018-03-01

Multiple experimental and clinical studies have identified pathways by which uric acid may facilitate the development and progression of chronic kidney disease (CKD) in people with diabetes. However, it remains uncertain if the association of uric acid with CKD represents a pathogenic effect or merely reflects renal impairment. In contrast to many published reports, a recent Mendelian randomization study did not identify a causal link between uric acid and CKD in people with type 1 diabetes. Two recent multicenter randomized control trials, Preventing Early Renal Function Loss in Diabetes (PERL) and FEbuxostat versus placebo rAndomized controlled Trial regarding reduced renal function in patients with Hyperuricemia complicated by chRonic kidney disease stage 3 (FEATHER), were recently designed to assess if uric acid lowering slows progression of CKD. We review the evidence supporting a role for uric acid in the pathogenesis of CKD in people with diabetes and the putative benefits of uric acid lowering.

Effects of medium-chain triglycerides on weight loss and body composition: a meta-analysis of randomized controlled trials.

PubMed

Mumme, Karen; Stonehouse, Welma

2015-02-01

Medium-chain triglycerides (MCTs) may result in negative energy balance and weight loss through increased energy expenditure and lipid oxidation. However, results from human intervention studies investigating the weight reducing potential of MCTs, have been mixed. To conduct a systematic review and meta-analysis of randomized controlled trials comparing the effects of MCTs, specifically C8:0 and C10:0, to long-chain triglycerides (LCTs) on weight loss and body composition in adults. Changes in blood lipid levels were secondary outcomes. Randomized controlled trials >3 weeks' duration conducted in healthy adults were identified searching Web of Knowledge, Discover, PubMed, Scopus, New Zealand Science, and Cochrane CENTRAL until March 2014 with no language restriction. Identified trials were assessed for bias. Mean differences were pooled and analyzed using inverse variance models with fixed effects. Heterogeneity between studies was calculated using I(2) statistic. An I(2)>50% or P<0.10 indicated heterogeneity. Thirteen trials (n=749) were identified. Compared with LCTs, MCTs decreased body weight (-0.51 kg [95% CI-0.80 to -0.23 kg]; P<0.001; I(2)=35%); waist circumference (-1.46 cm [95% CI -2.04 to -0.87 cm]; P<0.001; I(2)=0%), hip circumference (-0.79 cm [95% CI -1.27 to -0.30 cm]; P=0.002; I(2)=0%), total body fat (standard mean difference -0.39 [95% CI -0.57 to -0.22]; P<0.001; I(2)=0%), total subcutaneous fat (standard mean difference -0.46 [95% CI -0.64 to -0.27]; P<0.001; I(2)=20%), and visceral fat (standard mean difference -0.55 [95% CI -0.75 to -0.34]; P<0.001; I(2)=0%). No differences were seen in blood lipid levels. Many trials lacked sufficient information for a complete quality assessment, and commercial bias was detected. Although heterogeneity was absent, study designs varied with regard to duration, dose, and control of energy intake. Replacement of LCTs with MCTs in the diet could potentially induce modest reductions in body weight and composition without adversely affecting lipid profiles. However, further research is required by independent research groups using large, well-designed studies to confirm the efficacy of MCT and to determine the dosage needed for the management of a healthy body weight and composition. Copyright © 2015 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Integrating fragmented evidence by network meta-analysis: relative effectiveness of psychological interventions for adults with post-traumatic stress disorder.

PubMed

Gerger, H; Munder, T; Gemperli, A; Nüesch, E; Trelle, S; Jüni, P; Barth, J

2014-11-01

To summarize the available evidence on the effectiveness of psychological interventions for patients with post-traumatic stress disorder (PTSD). We searched bibliographic databases and reference lists of relevant systematic reviews and meta-analyses for randomized controlled trials that compared specific psychological interventions for adults with PTSD symptoms either head-to-head or against control interventions using non-specific intervention components, or against wait-list control. Two investigators independently extracted the data and assessed trial characteristics. The analyses included 4190 patients in 66 trials. An initial network meta-analysis showed large effect sizes (ESs) for all specific psychological interventions (ESs between -1.10 and -1.37) and moderate effects of psychological interventions that were used to control for non-specific intervention effects (ESs -0.58 and -0.62). ES differences between various types of specific psychological interventions were absent to small (ES differences between 0.00 and 0.27). Considerable between-trial heterogeneity occurred (τ²= 0.30). Stratified analyses revealed that trials that adhered to DSM-III/IV criteria for PTSD were associated with larger ESs. However, considerable heterogeneity remained. Heterogeneity was reduced in trials with adequate concealment of allocation and in large-sized trials. We found evidence for small-study bias. Our findings show that patients with a formal diagnosis of PTSD and those with subclinical PTSD symptoms benefit from different psychological interventions. We did not identify any intervention that was consistently superior to other specific psychological interventions. However, the robustness of evidence varies considerably between different psychological interventions for PTSD, with most robust evidence for cognitive behavioral and exposure therapies.

Cognitive impairment and PD patients' capacity to consent to research

PubMed Central

Cary, Mark; Moelter, Stephen T.; Siderowf, Andrew; Sullo, Elizabeth; Xie, Sharon; Weintraub, Daniel

2013-01-01

Objective: To examine how cognitive impairment affects Parkinson disease (PD) patients' research consent capacity. Methods: A cross-sectional study of 90 patients with PD, divided using Mattis Dementia Rating Scale–2 scores into 3 groups of 30 (normal, borderline, and impaired), and 30 neurologically normal older adults completed 2 capacity interviews (an early-phase randomized and controlled drug trial and a sham-controlled surgical implantation of genetic tissue) using the MacArthur Competence Assessment Tool for Clinical Research. Expert clinicians used the interviews to classify the patients as either capable or not capable of providing their own informed consent. These judgments were compared with performance on the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). Results: Cognitively normal PD patients typically scored well on the capacity measures. In contrast, patients with impaired cognition were not capable of providing their own informed consent: 17% (5/30) on the drug trial and 3% (1/30) on the surgery trial were judged capable. Patients with borderline impairment showed adequate performance on measures of appreciation and reasoning, but impaired performance on understanding the drug trial compared with normal controls and normal PD patients, and on understanding the surgery trial compared with normal controls. Sixty-seven percent (20/30) on the drug trial and 57% (17/30) on the surgery trial were judged capable of consent. Receiver operating characteristic analyses showed that the MMSE and MoCA could detect the likelihood of impaired capacity, with the MoCA demonstrating greater sensitivity. Conclusions: PD patients with borderline cognitive impairment have impairments in their decisional capacity. The MoCA may be useful to identify the patients at risk of impaired capacity. PMID:23892706

Effects of Electrical Stimulation in Spastic Muscles After Stroke: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Stein, Cinara; Fritsch, Carolina Gassen; Robinson, Caroline; Sbruzzi, Graciele; Plentz, Rodrigo Della Méa

2015-08-01

Neuromuscular electric stimulation (NMES) has been used to reduce spasticity and improve range of motion in patients with stroke. However, contradictory results have been reported by clinical trials. A systematic review of randomized clinical trials was conducted to assess the effect of treatment with NMES with or without association to another therapy on spastic muscles after stroke compared with placebo or another intervention. We searched the following electronic databases (from inception to February 2015): Medline (PubMed), EMBASE, Cochrane Central Register of Controlled Trials and Physiotherapy Evidence Database (PEDro). Two independent reviewers assessed the eligibility of studies based on predefined inclusion criteria (application of electric stimulation on the lower or upper extremities, regardless of NMES dosage, and comparison with a control group which was not exposed to electric stimulation), excluding studies with <3 days of intervention. The primary outcome extracted was spasticity, assessed by the Modified Ashworth Scale, and the secondary outcome extracted was range of motion, assessed by Goniometer. Of the total of 5066 titles, 29 randomized clinical trials were included with 940 subjects. NMES provided reductions in spasticity (-0.30 [95% confidence interval, -0.58 to -0.03], n=14 randomized clinical trials) and increase in range of motion when compared with control group (2.87 [95% confidence interval, 1.18-4.56], n=13 randomized clinical trials) after stroke. NMES combined with other intervention modalities can be considered as a treatment option that provides improvements in spasticity and range of motion in patients after stroke. URL: http://www.crd.york.ac.uk/PROSPERO. Unique identifier: CRD42014008946. © 2015 American Heart Association, Inc.

Surrogate endpoints for overall survival in combined chemotherapy and radiotherapy trials in nasopharyngeal carcinoma: Meta-analysis of randomised controlled trials.

PubMed

Chen, Yu-Pei; Sun, Ying; Chen, Lei; Mao, Yan-Ping; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Zhang, Wen-Na; Zhou, Guan-Qun; Guo, Rui; Lin, Ai-Hua; Ma, Jun

2015-08-01

We used a literature-based meta-analysis to assess whether failure-free survival (FFS) or progression-free survival (PFS) could be reliable surrogate endpoints for overall survival (OS) in trials of combined chemotherapy and radiotherapy for nasopharyngeal carcinoma (NPC). We identified randomised trials that evaluated combined chemoradiotherapy strategies, and reported FFS or PFS and OS in NPC. We analysed the treatment effects on FFS or PFS, and OS. We used the coefficient of determination (R(2)), and the surrogate threshold effect (STE) to assess the trial-level correlation. Twenty-one trials (5212 patients), with sixteen treatment-control comparisons for FFS, and nine for PFS, were analysed. FFS was strongly correlated with OS (R(2)=0.88, STE=0.84), as was PFS (R(2)=0.90, STE=0.88). Moreover, FFS and PFS at 3 years were still strongly correlated with 5-year OS (R(2)=0.80, STE=0.83; R(2)=0.85, STE=0.84). Both FFS and PFS could be valid surrogate endpoints for OS in trials of combined chemotherapy and radiotherapy for NPC; PFS may be a more acceptable surrogate endpoint compared with FFS. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Herbal medicines for treating acute otitis media: A systematic review of randomised controlled trials.

PubMed

Son, Mi Ju; Kim, Young-Eun; Song, Young Il; Kim, Yun Hee

2017-12-01

This systematic review aimed to assess the clinical evidence for the widespread use of herbal medicines in treating acute otitis media. Eleven electronic databases, including MEDLINE, EMBASE, and the CENTRAL were searched, without language limitations. All randomised controlled trials involving the use of herbal medicines, alone or in combination with conventional therapies, for acute otitis media were included. We identified 4956 studies, of which seven randomised clinical trials met the inclusion criteria. The overall risk of bias of the included trials was relatively high or unclear. Treatment with Longdan-xiegan decoction or Shenling-baizhu powder, combined with antibiotics, appeared to be more effective than treatment with antibiotics alone in terms of the proportion of patients with total symptom recovery. Moreover, combination treatment of Sinupret ® and antibiotics facilitated the recovery of middle ear conditions and hearing acuity. Despite some indications of potential symptom improvement, the evidence regarding the effectiveness and efficacy of herbal medicine for acute otitis media is inconclusive due to the poor quality of trials included. Moreover, we only analysed seven trials in this review. Therefore, to properly evaluate the effectiveness of herbal medicine for acute otitis media, systematic reviews based on more rigorously designed randomized trials are warranted in the future. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Glucocorticosteroids for infants with biliary atresia following Kasai portoenterostomy.

PubMed

Tyraskis, Athanasios; Parsons, Christopher; Davenport, Mark

2018-05-14

Biliary atresia is a life-threatening disease characterised by progressive destruction of both intra- and extra-hepatic biliary ducts. The mainstay of treatment is Kasai portoenterostomy, as soon as the disease has been confirmed. Glucocorticosteroids are steroid hormones which act on the glucocorticoid receptor and have a range of metabolic and immunomodulatory effects. Glucocorticosteroids are used to improve the postoperative outcomes in infants who have undergone Kasai portoenterostomy. To assess the beneficial and harmful effects of glucocorticosteroid administration versus placebo or no intervention following Kasai portoenterostomy in infants with biliary atresia. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE Ovid, Embase Ovid, Science Citation Index Expanded (Web of Science), and online trial registries (last search: 20 December 2017) for randomised controlled trials. We included randomised clinical trials which assessed glucocorticosteroids for infants who have undergone Kasai portoenterostomy. For harm, we also considered quasi-randomised studies, observational studies, and case-control studies that were identified amongst the search results. We used standard methodological procedures expected by Cochrane. We assessed the risk of bias for each trial according to prespecified domains. We analysed data using both random-effects and fixed-effect models. We performed the analyses using Review Manager 5.3 and Trial Sequental Analysis software. We considered a P value of 0.025 or less, two-tailed, as statistically significant. We planned to calculate risk ratios (RRs) for dichotomous outcomes, and the mean difference (MD) for continuous outcomes. For all association measures, we planned to use 95% confidence intervals (CIs) as well as Trial Sequential Analysis-adjusted CIs. We used Trial Sequential Analyisis to control the risks of random errors; however, we were often unable to implement this beyond calculating the required information size as there were few trials and data. We assessed the certainty of the evidence using GRADE. We found two randomised controlled trials fulfilling the inclusion criteria of our review. The trials provided data for meta-analysis. We judged the two trials as trials at low risk of bias. The two trials randomised a total of 213 infants to glucocorticosteroids versus placebo. In our Trial Sequential Analysis, the required information size (that is, the meta-analytic sample size) was not reached for any outcome. Trials were funded by charities, public organisations, and received support from private sector companies, none of which seemed to have an interest in the outcome of the respective trials. The effect of glucocorticosteroids after Kasai portoenterostomy on all-cause mortality is uncertain; the confidence interval is consistent with appreciable benefit and harm (RR 1.00; 95% CI 0.14 to 6.90; low-certainty evidence). The results showed little or no difference in adverse effects between the use of glucocorticosteroids or placebo after Kasai portoenterostomy, however this analysis was based on a single trial and we have low certainty in the result (RR 1.02; 95% CI 0.87 to 1.20;). Available data suggest that the proportions of infants who do not clear their jaundice at six months is similar between the two groups (RR 0.89; 95% CI 0.67 to 1.17; low-certainty evidence). All-cause mortality or liver transplantation did not differ at two years between the two groups (RR 1.00; 95% CI 0.72 to 1.39; low-certainty evidence). There were no data regarding health-related quality of life.Our searches also yielded 19 observational studies, some of them containing limited information on harmful effects of glucocorticosteroid treatment. We presented the extracted information narratively. We identified one further ongoing trial with no currently available results. The two meta-analysed randomised clinical trials present insufficient evidence to determine the effects of using glucocorticosteroids versus placebo after Kasai portoenterostomy in infants with biliary atresia on any of the primary or secondary review outcomes. There is insufficient evidence to support glucocorticosteroid use in the postoperative management of infants with biliary atresia for long-term outcomes of all-cause mortality or liver transplantation. It is also unclear if glucocorticosteroids are able to reduce the numbers of infants who did not clear their jaundice by six months. Further randomised, placebo-controlled trials are required to be able to determine if glucocorticosteroids may be of benefit in the postoperative management of infants with biliary atresia treated with Kasai portoenterostomy. Such trials need to be conducted as multicentre trials.

An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom

PubMed Central

2012-01-01

Background To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation. Methods An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews. Results The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises. Conclusions It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability. Trial registration UKCRN 7090; ISRCTN: 80875696 PMID:22676069

Tilt Table Therapies for Patients with Severe Disorders of Consciousness: A Randomized, Controlled Trial

PubMed Central

Krewer, Carmen; Luther, Marianne; Koenig, Eberhard; Müller, Friedemann

2015-01-01

One major aim of the neurological rehabilitation of patients with severe disorders of consciousness (DOC) is to enhance patients’ arousal and ability to communicate. Mobilization into a standing position by means of a tilt table has been shown to improve their arousal and awareness. However, due to the frequent occurrence of syncopes on a tilt table, it is easier to accomplish verticalization using a tilt table with an integrated stepping device. The objective of this randomized controlled clinical trial was to evaluate the effectiveness of a tilt table therapy with or without an integrated stepping device on the level of consciousness. A total of 50 participants in vegetative or minimally conscious states 4 weeks to 6 month after injury were treated with verticalization during this randomized controlled trial. Interventions involved ten 1-hour sessions of the specific treatment over a 3-week period. Blinded assessors made measurements before and after the intervention period, as well as after a 3-week follow-up period. The coma recovery scale-revised (CRS-R) showed an improvement by a median of 2 points for the group receiving tilt table with integrated stepping (Erigo). The rate of recovery of the group receiving the conventional tilt table therapy significantly increased by 5 points during treatment and by an additional 2 points during the 3-week follow-up period. Changes in spasticity did not significantly differ between the two intervention groups. Compared to the conventional tilt table, the tilt table with integrated stepping device failed to have any additional benefit for DOC patients. Verticalization itself seems to be beneficial though and should be administered to patients in DOC in early rehabilitation. Trial Registration: Current Controlled Trials Ltd (www.controlled-trials.com), identifier number ISRCTN72853718 PMID:26623651

Tilt Table Therapies for Patients with Severe Disorders of Consciousness: A Randomized, Controlled Trial.

PubMed

Krewer, Carmen; Luther, Marianne; Koenig, Eberhard; Müller, Friedemann

2015-01-01

One major aim of the neurological rehabilitation of patients with severe disorders of consciousness (DOC) is to enhance patients' arousal and ability to communicate. Mobilization into a standing position by means of a tilt table has been shown to improve their arousal and awareness. However, due to the frequent occurrence of syncopes on a tilt table, it is easier to accomplish verticalization using a tilt table with an integrated stepping device. The objective of this randomized controlled clinical trial was to evaluate the effectiveness of a tilt table therapy with or without an integrated stepping device on the level of consciousness. A total of 50 participants in vegetative or minimally conscious states 4 weeks to 6 month after injury were treated with verticalization during this randomized controlled trial. Interventions involved ten 1-hour sessions of the specific treatment over a 3-week period. Blinded assessors made measurements before and after the intervention period, as well as after a 3-week follow-up period. The coma recovery scale-revised (CRS-R) showed an improvement by a median of 2 points for the group receiving tilt table with integrated stepping (Erigo). The rate of recovery of the group receiving the conventional tilt table therapy significantly increased by 5 points during treatment and by an additional 2 points during the 3-week follow-up period. Changes in spasticity did not significantly differ between the two intervention groups. Compared to the conventional tilt table, the tilt table with integrated stepping device failed to have any additional benefit for DOC patients. Verticalization itself seems to be beneficial though and should be administered to patients in DOC in early rehabilitation. Trial Registration: Current Controlled Trials Ltd (www.controlled-trials.com), identifier number ISRCTN72853718.

Effect of Information and Telephone-Guided Access to Community Support for People with Chronic Kidney Disease: Randomised Controlled Trial

PubMed Central

Blakeman, Tom; Blickem, Christian; Kennedy, Anne; Reeves, David; Bower, Peter; Gaffney, Hannah; Gardner, Caroline; Lee, Victoria; Jariwala, Praksha; Dawson, Shoba; Mossabir, Rahena; Brooks, Helen; Richardson, Gerry; Spackman, Eldon; Vassilev, Ivaylo; Chew-Graham, Carolyn; Rogers, Anne

2014-01-01

Background Implementation of self-management support in traditional primary care settings has proved difficult, encouraging the development of alternative models which actively link to community resources. Chronic kidney disease (CKD) is a common condition usually diagnosed in the presence of other co-morbidities. This trial aimed to determine the effectiveness of an intervention to provide information and telephone-guided access to community support versus usual care for patients with stage 3 CKD. Methods and Findings In a pragmatic, two-arm, patient level randomised controlled trial 436 patients with a diagnosis of stage 3 CKD were recruited from 24 general practices in Greater Manchester. Patients were randomised to intervention (215) or usual care (221). Primary outcome measures were health related quality of life (EQ-5D health questionnaire), blood pressure control, and positive and active engagement in life (heiQ) at 6 months. At 6 months, mean health related quality of life was significantly higher for the intervention group (adjusted mean difference = 0.05; 95% CI = 0.01, 0.08) and blood pressure was controlled for a significantly greater proportion of patients in the intervention group (adjusted odds-ratio = 1.85; 95% CI = 1.25, 2.72). Patients did not differ significantly in positive and active engagement in life. The intervention group reported a reduction in costs compared with control. Conclusions An intervention to provide tailored information and telephone-guided access to community resources was associated with modest but significant improvements in health related quality of life and better maintenance of blood pressure control for patients with stage 3 CKD compared with usual care. However, further research is required to identify the mechanisms of action of the intervention. Trial Registration Controlled-Trials.com ISRCTN45433299 PMID:25330169

Stem Cell Trials for Cardiovascular Medicine: Ethical Rationale

PubMed Central

Teraa, Martin; Hesam, Husna; van Delden, Johannes J.M.; Verhaar, Marianne C.; Bredenoord, Annelien L.

2014-01-01

Stem cell-based interventions provide new treatment prospects for many disease conditions, including cardiovascular disorders. Clinical trials are necessary to collect adequate evidence on (long-term) safety and efficacy of novel interventions such as stem cells, but the design and launch of clinical trials, from first-in-human studies to larger randomized controlled trials (RCTs), is scientifically and ethically challenging. Stem cells are different from traditional pharmaceuticals, surgical procedures, and medical devices in the following ways: the novelty and complexity of stem cells, the invasiveness of the procedures, and the novel aim of regeneration. These specifics, combined with the characteristics of the study population, will have an impact on the design and ethics of RCTs. The recently closed JUVENTAS trial will serve as an example to identify the (interwoven) scientific and ethical challenges in the design and launch of stem cell RCTs. The JUVENTAS trial has investigated the efficacy of autologous bone marrow cells in end-stage vascular patients, in a double-blind sham-controlled design. We first describe the choices, considerations, and experiences of the JUVENTAS team. Subsequently, we identify the main ethical and scientific challenges and discuss what is important to consider in the design of future stem cell RCTs: assessment of risks and benefits, the choice for outcome measures, the choice for the comparator, the appropriate selection of participants, and adequate informed consent. Additionally, the stem cell field is highly in the spotlight due to the (commercial) interests and expectations. This warrants a cautious pace of translation and scrupulous set up of clinical trials, as failures could put the field in a negative light. At the same time, knowledge from clinical trials is necessary for the field to progress. We conclude that in the scientifically and ethically challenging field of stem cell RCTs, researchers and clinicians have to maneuver between the Skylla of hyper accelerated translation without rigorously conducted RCTs and the Charybdis of the missed opportunity of valuable knowledge. PMID:24164351

Culturally adaptive storytelling method to improve hypertension control in Vietnam - "We talk about our hypertension": study protocol for a feasibility cluster-randomized controlled trial.

PubMed

Allison, Jeroan J; Nguyen, Hoa L; Ha, Duc A; Chiriboga, Germán; Ly, Ha N; Tran, Hanh T; Phan, Ngoc T; Vu, Nguyen C; Kim, Minjin; Goldberg, Robert J

2016-01-14

Vietnam is experiencing an epidemiologic transition with an increased prevalence of non-communicable diseases. At present, the major risk factors for cardiovascular disease (CVD) are either on the rise or at alarming levels in Vietnam; inasmuch, the burden of CVD will continue to increase in this country unless effective prevention and control measures are put in place. A national survey in 2008 found that the prevalence of hypertension (HTN) was approximately 25 % among Vietnamese adults and it increased with advancing age. Therefore, novel, large-scale, and sustainable interventions for public health education to promote engagement in the process of detecting and treating HTN in Vietnam are urgently needed. A feasibility randomized trial will be conducted in Hung Yen province, Vietnam to evaluate the feasibility and acceptability of a novel community-based intervention using the "storytelling" method to enhance the control of HTN in adults residing in four rural communities. The intervention will center on stories about living with HTN, with patients speaking in their own words. The stories will be obtained from particularly eloquent patients, or "video stars," identified during Story Development Groups. The study will involve two phases: (i) developing a HTN intervention using the storytelling method, which is designed to empower patients to facilitate changes in their lifestyle practices, and (ii) conducting a feasibility cluster-randomized trial to investigate the feasibility, acceptability, and potential efficacy of the intervention compared with usual care in HTN control among rural residents. The trial will be conducted at four communes, and within each commune, 25 individuals 50 years or older with HTN will be enrolled in the trial resulting in a total sample size of 100 patients. This feasibility trial will provide the necessary groundwork for a subsequent large-scale, fully powered, cluster-randomized controlled trial to test the efficacy of our novel community-based intervention. Results from the full-scale trial will provide health policy makers with practical evidence on how to combat a key risk factor for CVD using a feasible, sustainable, and cost-effective intervention that could be used as a national program for controlling HTN in Vietnam and other developing countries. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02483780 (registration date June 22, 2015).

Association between exogenous testosterone and cardiovascular events: an overview of systematic reviews.

PubMed

Onasanya, Oluwadamilola; Iyer, Geetha; Lucas, Eleanor; Lin, Dora; Singh, Sonal; Alexander, G Caleb

2016-11-01

Given the conflicting evidence regarding the association between exogenous testosterone and cardiovascular events, we systematically assessed published systematic reviews for evidence of the association between exogenous testosterone and cardiovascular events. We searched PubMed, MEDLINE, Embase, Cochrane Collaboration Clinical Trials, ClinicalTrials.gov, and the US Food and Drug Administration website for systematic reviews of randomised controlled trials published up to July 19, 2016. Two independent reviewers screened 954 full texts from 29 335 abstracts to identify systematic reviews of randomised controlled trials in which the cardiovascular effects of exogenous testosterone on men aged 18 years or older were examined. We extracted data for study characteristics, analytic methods, and key findings, and applied the AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist to assess methodological quality of each review. Our primary outcome measure was the direction and magnitude of association between exogenous testosterone and cardiovascular events. We identified seven reviews and meta-analyses, which had substantial clinical heterogeneity, differing statistical methods, and variable methodological quality and quality of data abstraction. AMSTAR scores ranged from 3 to 9 out of 11. Six systematic reviews that each included a meta-analysis showed no significant association between exogenous testosterone and cardiovascular events, with summary estimates ranging from 1·07 to 1·82 and imprecise confidence intervals. Two of these six meta-analyses showed increased risk in subgroup analyses of oral testosterone and men aged 65 years or older during their first treatment year. One meta-analysis showed a significant association between exogenous testosterone and cardiovascular events, in men aged 18 years or older generally, with a summary estimate of 1·54 (95% CI 1·09-2·18). Our optimal information size analysis showed that any randomised controlled trial aiming to detect a true difference in cardiovascular risk between treatment groups receiving exogenous testosterone and their controls (with a two-sided p value of 0·05 and a power of 80%) would require at least 17 664 participants in each trial group. Therefore, given the challenge of adequately powering clinical trials for rare outcomes, rigorous observational studies are needed to clarify the association between testosterone-replacement therapy and major adverse cardiovascular outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of the effect of patient education on rates of falls in older hospital patients: Description of a randomised controlled trial

PubMed Central

Hill, Anne-Marie; Hill, Keith; Brauer, Sandra; Oliver, David; Hoffmann, Tammy; Beer, Christopher; McPhail, Steven; Haines, Terry P

2009-01-01

Background Accidental falls by older patients in hospital are one of the most commonly reported adverse events. Falls after discharge are also common. These falls have enormous physical, psychological and social consequences for older patients, including serious physical injury and reduced quality of life, and are also a source of substantial cost to health systems worldwide. There have been a limited number of randomised controlled trials, mainly using multifactorial interventions, aiming to prevent older people falling whilst inpatients. Trials to date have produced conflicting results and recent meta-analyses highlight that there is still insufficient evidence to clearly identify which interventions may reduce the rate of falls, and falls related injuries, in this population. Methods and design A prospective randomised controlled trial (n = 1206) is being conducted at two hospitals in Australia. Patients are eligible to be included in the trial if they are over 60 years of age and they, or their family or guardian, give written consent. Participants are randomised into three groups. The control group continues to receive usual care. Both intervention groups receive a specifically designed patient education intervention on minimising falls in addition to usual care. The education is delivered by Digital Video Disc (DVD) and written workbook and aims to promote falls prevention activities by participants. One of the intervention groups also receives follow up education training visits by a health professional. Blinded assessors conduct baseline and discharge assessments and follow up participants for 6 months after discharge. The primary outcome measure is falls by participants in hospital. Secondary outcome measures include falls at home after discharge, knowledge of falls prevention strategies and motivation to engage in falls prevention activities after discharge. All analyses will be based on intention to treat principle. Discussion This trial will examine the effect of a single intervention (specifically designed patient education) on rates of falls in older patients in hospital and after discharge. The results will provide robust recommendations for clinicians and researchers about the role of patient education in this population. The study has the potential to identify a new intervention that may reduce rates of falls in older hospital patients and could be readily duplicated and applied in a wide range of clinical settings. Trial Registration ACTRN12608000015347 PMID:19393046

Podiatry intervention versus usual care to prevent falls in care homes: pilot randomised controlled trial (the PIRFECT study).

PubMed

Wylie, Gavin; Menz, Hylton B; McFarlane, Sarah; Ogston, Simon; Sullivan, Frank; Williams, Brian; Young, Zoe; Morris, Jacqui

2017-07-12

Common foot problems are independent risk factors for falls in older people. There is evidence that podiatry can prevent falls in community-dwelling populations. The feasibility of implementing a podiatry intervention and trial in the care home population is unknown. To inform a potential future definitive trial, we performed a pilot randomised controlled trial to assess: (i) the feasibility of a trial of a podiatry intervention to reduce care home falls, and (ii) the potential direction and magnitude of the effect of the intervention in terms of number of falls in care home residents. Informed by Medical Research Council guidance on developing and evaluating complex interventions, we conducted a single blind, pilot randomised controlled trial in six care homes in the East of Scotland. Participants were randomised to either: (i) a three month podiatry intervention comprising core podiatry care, foot and ankle exercises, orthoses and footwear provision or (ii) usual care. Falls-related outcomes (number of falls, time to first fall) and feasibility-related outcomes (recruitment, retention, adherence, data collection rates) were collected. Secondary outcomes included: generic health status, balance, mobility, falls efficacy, and ankle joint strength. 474 care home residents were screened. 43 (9.1%) participants were recruited: 23 to the intervention, 20 to control. Nine (21%) participants were lost to follow-up due to declining health or death. It was feasible to deliver the trial elements in the care home setting. 35% of participants completed the exercise programme. 48% reported using the orthoses 'all or most of the time'. Completion rates of the outcome measures were between 93% and 100%. No adverse events were reported. At the nine month follow-up period, the intervention group per-person fall rate was 0.77 falls vs. 0.83 falls in the control group. A podiatry intervention to reduce falls can be delivered to care home residents within a pilot randomised controlled trial of the intervention. Although not powered to determine effectiveness, these preliminary data provide justification for a larger trial, incorporating a full process evaluation, to determine whether this intervention can significantly reduce falls in this high-risk population. ClinicalTrials.gov identifier: NCT02178527 ; Date of registration: 17 June 2014.

A matter of timing: harm reduction in learned helplessness.

PubMed

Richter, Sophie Helene; Sartorius, Alexander; Gass, Peter; Vollmayr, Barbara

2014-11-03

Learned helplessness has excellent validity as an animal model for depression, but problems in reproducibility limit its use and the high degree of stress involved in the paradigm raises ethical concerns. We therefore aimed to identify which and how many trials of the learned helplessness paradigm are necessary to distinguish between helpless and non-helpless rats. A trial-by-trial reanalysis of tests from 163 rats with congenital learned helplessness or congenital non-learned helplessness and comparison of 82 rats exposed to inescapable shock with 38 shock-controls revealed that neither the first test trials, when rats showed unspecific hyperlocomotion, nor trials of the last third of the test, when almost all animals responded quickly to the stressor, contributed to sensitivity and specificity of the test. Considering only trials 3-10 improved the classification of helpless and non-helpless rats. The refined analysis allows abbreviation of the test for learned helplessness from 15 trials to 10 trials thereby reducing pain and stress of the experimental animals without losing statistical power.

Mediterranean Diet and Invasive Breast Cancer Risk Among Women at High Cardiovascular Risk in the PREDIMED Trial: A Randomized Clinical Trial.

PubMed

Toledo, Estefanía; Salas-Salvadó, Jordi; Donat-Vargas, Carolina; Buil-Cosiales, Pilar; Estruch, Ramón; Ros, Emilio; Corella, Dolores; Fitó, Montserrat; Hu, Frank B; Arós, Fernando; Gómez-Gracia, Enrique; Romaguera, Dora; Ortega-Calvo, Manuel; Serra-Majem, Lluís; Pintó, Xavier; Schröder, Helmut; Basora, Josep; Sorlí, José Vicente; Bulló, Mònica; Serra-Mir, Merce; Martínez-González, Miguel A

2015-11-01

Breast cancer is the leading cause of female cancer burden, and its incidence has increased by more than 20% worldwide since 2008. Some observational studies have suggested that the Mediterranean diet may reduce the risk of breast cancer. To evaluate the effect of 2 interventions with Mediterranean diet vs the advice to follow a low-fat diet (control) on breast cancer incidence. The PREDIMED study is a 1:1:1 randomized, single-blind, controlled field trial conducted at primary health care centers in Spain. From 2003 to 2009, 4282 women aged 60 to 80 years and at high cardiovascular disease risk were recruited after invitation by their primary care physicians. Participants were randomly allocated to a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Breast cancer incidence was a prespecified secondary outcome of the trial for women without a prior history of breast cancer (n = 4152). After a median follow-up of 4.8 years, we identified 35 confirmed incident cases of breast cancer. Observed rates (per 1000 person-years) were 1.1 for the Mediterranean diet with extra-virgin olive oil group, 1.8 for the Mediterranean diet with nuts group, and 2.9 for the control group. The multivariable-adjusted hazard ratios vs the control group were 0.32 (95% CI, 0.13-0.79) for the Mediterranean diet with extra-virgin olive oil group and 0.59 (95% CI, 0.26-1.35) for the Mediterranean diet with nuts group. In analyses with yearly cumulative updated dietary exposures, the hazard ratio for each additional 5% of calories from extra-virgin olive oil was 0.72 (95% CI, 0.57-0.90). This is the first randomized trial finding an effect of a long-term dietary intervention on breast cancer incidence. Our results suggest a beneficial effect of a Mediterranean diet supplemented with extra-virgin olive oil in the primary prevention of breast cancer. These results come from a secondary analysis of a previous trial and are based on few incident cases and, therefore, need to be confirmed in longer-term and larger studies. ISRCTN.org Identifier: ISRCTN35739639.

How do hospital professionals involved in a randomised controlled trial perceive the value of genotyping vs. PCR-ribotyping for control of hospital acquired C. difficile infections?

PubMed Central

2014-01-01

Background Despite scientific advances in typing of C. difficile strains very little is known about how hospital staff use typing results during periods of increased incidence (PIIs). This qualitative study, undertaken alongside a randomised controlled trial (RCT), explored this issue. The trial compared ribotyping versus more rapid genotyping (MLVA or multilocus variable repeat analysis) and found no significant difference in post 48 hour cases (C difficile transmissions). Methods In-depth qualitative interviews with senior staff in 11/16 hospital trusts in the trial (5 MLVA and 6 Ribotyping). Semi-structured interviews were conducted at end of the trial period. Transcripts were content analysed using framework analysis supported by NVivo-8 software. Common sub-themes were extracted by two researchers independently. These were compared and organised into over-arching categories or ‘super-ordinate themes’. Results The trial recorded that 45% of typing tests had some impact on infection control (IC) activities. Interviews indicated that tests had little impact on initial IC decisions. These were driven by hospital protocols and automatically triggered when a PII was identified. To influence decision-making, a laboratory turnaround time < 3 days (ideally 24 hours) was suggested; MLVA turnaround time was 5.3 days. Typing results were predominantly used to modify initiated IC activities such as ward cleaning, audits of practice or staff training; major decisions (e.g. ward closure) were unaffected. Organisational factors could limit utilisation of MLVA results. Results were twice as likely to be reported as ‘aiding management’ (indirect benefit) than impacting on IC activities (direct effect). Some interviewees considered test results provided reassurance about earlier IC decisions; others identified secondary benefits on organisational culture. An underlying benefit of improved discrimination provided by MLVA typing was the ability to explore epidemiology associated with CDI cases in a hospital more thoroughly. Conclusions Ribotyping and MLVA are both valued by users. MLVA had little additional direct impact on initial infection control decisions. This would require reduced turnaround time. The major impact is adjustments to earlier IC measures and retrospective reassurance. For this, turnaround time is less important than discriminatory power. The potential remains for wider use of genotyping to examine transmission routes. PMID:24656142

A comparison of speech and language therapy techniques for dysarthria in Parkinson's disease.

PubMed

Deane, K H; Whurr, R; Playford, E D; Ben-Shlomo, Y; Clarke, C E

2001-01-01

Dysarthria is a common manifestation of Parkinson's disease that increases in frequency and intensity with the progress of the disease (Streifler 1984). Up to 20% of Parkinsonian patients are referred for speech and language therapy (S & LT), its aim being to improve the intelligibility of the patient's speech. To compare the efficacy and effectiveness of novel S & LT techniques versus standard S & LT to treat dysarthria in patients with Parkinson's disease. To compare the efficacy and effectiveness of one S & LT technique versus a second form of S & LT to treat Parkinsonian dysarthria. Relevant trials were identified by electronic searches of MEDLINE, EMBASE, CINAHL, ISI-SCI, AMED, MANTIS, REHABDATA, REHADAT, GEROLIT, Pascal, LILACS, MedCarib, JICST-EPlus, AIM, IMEMR, SIGLE, ISI-ISTP, DISSABS, Conference Papers Index, Aslib Index to Theses, the Cochrane Controlled Trials Register, the CentreWatch Clinical Trials listing service, the metaRegister of Controlled Trials, ClinicalTrials.gov, CRISP, PEDro, NIDRR and NRR; and examination of the reference lists of identified studies and other reviews. Only randomised controlled trials (RCT) were included. Data was abstracted independently by KD and RW and differences settled by discussion. Only two trials were identified with only 71 patients. The method of randomisation was good in only one trial and the concealment of allocation was inadequate in both trials. These methodological problems could potentially lead to bias from a number of sources. The methods used in the two studies varied so much that meta-analysis of the results was not possible. Scott 83 compared prosodic exercises with visual cues with prosodic exercises alone (See Glossary: Table 01). The authors examined prosody and intelligibility as outcome measures immediately after therapy. Ramig 95 compared the Lee Silverman Voice Therapy (LSVT) which emphasises increased vocal effort, with respiratory therapy which aimed to increase respiratory muscle activity. Ramig 95 examined a wide range of vocal characteristics, activities of daily living affected by speech, depression and the carer's impressions of the patient's speech quality. Some of these outcomes were measured up to 24 months after the end of the therapy. However, in neither study were changes in outcomes due to 'Therapy A' compared with the changes due to 'Therapy B' statistically. Therefore no comment on the comparative efficacy of these types of speech and language therapy can be made. Considering the methodological flaws in both of these studies, the small number of patients examined, and the possibility of publication bias, there is insufficient evidence to support or refute the efficacy of any given form of S & LT over another to treat dysarthria in Parkinson's disease. Given the lack of evidence from RCTs to support or refute the efficacy of S & LT in Parkinson's disease (see Cochrane review 'Speech and Language therapy for Dysarthria in Patients with Parkinson's Disease'), the consensus as to what is considered 'best-practice' S & LT must be proved first through a large well-designed placebo-controlled randomised trial before examining variations in S & LT methodology. The design of these trials should minimise bias and be reported fully using CONSORT guidelines (CONSORT 1996). Outcome measures with particular relevance to patients, their carers, physicians and speech and language therapists should be chosen and the patients followed for at least 6 months to determine the duration of any improvement.

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.

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.

Job retention vocational rehabilitation for employed people with inflammatory arthritis (WORK-IA): a feasibility randomized controlled trial.

PubMed

Hammond, Alison; O'Brien, Rachel; Woodbridge, Sarah; Bradshaw, Lucy; Prior, Yeliz; Radford, Kate; Culley, June; Whitham, Diane; Ruth Pulikottil-Jacob

2017-07-21

Inflammatory arthritis leads to work disability, absenteeism and presenteeism (i.e. at-work productivity loss) at high cost to individuals, employers and society. A trial of job retention vocational rehabilitation (VR) in the United States identified this helped people keep working. The effectiveness of this VR in countries with different socioeconomic policies and conditions, and its impact on absenteeism, presenteeism and health, are unknown. This feasibility study tested the acceptability of this VR, modified for the United Kingdom, compared to written advice about managing work problems. To help plan a randomized controlled trial, we tested screening, recruitment, intervention delivery, response rates, applicability of the control intervention and identified the relevant primary outcome. A feasibility randomized controlled trial with rheumatoid, psoriatic or inflammatory arthritis patients randomized to receive either job retention VR or written information only (the WORK-IA trial). Following three days VR training, rheumatology occupational therapists provided individualised VR on a one to one basis. VR included work assessment, activity diaries and action planning, and (as applicable) arthritis self-management in the workplace, ergonomics, fatigue and stress management, orthoses, employment rights and support services, assistive technology, work modifications, psychological and disclosure support, workplace visits and employer liaison. Fifty five (10%) people were recruited from 539 screened. Follow-up response rates were acceptable at 80%. VR was delivered with fidelity. VR was more acceptable than written advice only (7.8 versus 6.7). VR took on average 4 h at a cost of £135 per person. Outcome assessment indicated VR was better than written advice in reducing presenteeism (Work Limitations Questionnaire (WLQ) change score mean: VR = -12.4 (SD 13.2); control = -2.5 (SD 15.9), absenteeism, perceived risk of job loss and improving pain and health status, indicating proof of concept. The preferred primary outcome measure was the WLQ, a presenteeism measure. This brief job retention VR is a credible and acceptable intervention for people with inflammatory arthritis with concerns about continuing to work due to arthritis. ISRCTN 76777720 . Registered 21.9.12.

Effectiveness of different nursing handover styles for ensuring continuity of information in hospitalised patients.

PubMed

Smeulers, Marian; Lucas, Cees; Vermeulen, Hester

2014-06-24

An accurate handover of clinical information is of great importance to continuity and safety of care. If clinically relevant information is not shared accurately and in a timely manner it may lead to adverse events, delays in treatment and diagnosis, inappropriate treatment and omission of care. During the last decade the call for interventions to improve handovers has increased. These interventions aim to reduce the risk of miscommunication, misunderstanding and the omission of critical information. To determine the effectiveness of interventions designed to improve hospital nursing handover, specifically:to identify which nursing handover style(s) are associated with improved outcomes for patients in the hospital setting and which nursing handover style(s) are associated with improved nursing process outcomes. We searched the following electronic databases for primary studies: Cochrane EPOC Group specialised register (to 19 September 2012), Cochrane Central Register of Controlled Trials (CENTRAL) (to 1 March 2013), MEDLINE (1950 to 1 March 2013) OvidSP, EMBASE (1947 to 1 March 2013) OvidSP, CINAHL (Cumulative Index to Nursing and Allied Health Literature) (1980 to 1 March 2013) EbscoHost and ISI Web of Knowledge (Science Citation Index and Social Sciences Citation Index) (to 9 July 2012). The Database of Abstracts of Reviews (DARE) was searched for related reviews. We screened the reference lists of included studies and relevant reviews. We also searched the WHO International Clinical Trials Registry Platform (ICTRP) http://www.who.int/ictrp/en/ and Current Controlled Trials www.controlled-trials.com/mrct and we conducted a search of grey literature web sites. Randomised controlled trials (RCTs or cluster-RCTs) evaluating any nursing handover style between nurses in a hospital setting with the aim of preventing adverse events or optimising the transfer of accurate essential information required for continuity of care, or both. Two review authors independently assessed trial quality and extracted data. The search identified 2178 citations, 28 of which were considered potentially relevant. After independent review of the full text of these studies, no eligible studies were identified for inclusion in this review due to the absence of studies with a randomised controlled study design. There was no evidence available to support conclusions about the effectiveness of nursing handover styles for ensuring continuity of information in hospitalised patients because we found no studies that fulfilled the methodological criteria for this review. As a consequence, uncertainty about the most effective practice remains. Research efforts should focus on strengthening the evidence abut the effectiveness of nursing handover styles using well designed, rigorous studies. According to current knowledge, the following guiding principles can be applied when redesigning the nursing handover process: face-to-face communication, structured documentation, patient involvement and use of IT technology to support the process.

Impact of a deferred recruitment model in a randomised controlled trial in primary care (CREAM study).

PubMed

Shepherd, Victoria; Thomas-Jones, Emma; Ridd, Matthew J; Hood, Kerenza; Addison, Katy; Francis, Nick A

2017-11-10

Recruitment of participants is particularly challenging in primary care, with less than a third of randomised controlled trials (RCT) achieving their target within the original time frame. Participant identification, consent, randomisation and data collection can all be time-consuming. Trials recruiting an incident, as opposed to a prevalent, population may be particularly affected. This paper describes the impact of a deferred recruitment model in a RCT of antibiotics for children with infected eczema in primary care, which required the recruitment of cases presenting acutely. Eligible children were identified by participating general practitioners (GPs) and referred to a study research nurse, who then visited them at home. This allowed the consent and recruitment processes to take place outside the general practice setting. Information was recorded about patients who were referred and recruited, or if not, the reasons for non-recruitment. Data on recruitment challenges were collected through semi-structured interviews and questionnaires with a sample of participating GPs. Data were thematically analysed to identify key themes. Of the children referred to the study 34% (58/171) were not recruited - 48% (28/58) because of difficulties arranging a baseline visit within the defined time frame, 31% (18/58) did not meet the study inclusion criteria at the time of nurse assessment, and 21% (12/58) declined participation. GPs had positive views about the recruitment process, reporting that parents valued and benefitted from additional contact with a nurse. GPs felt that the deferred recruitment model did not negatively impact on the study. GPs and parents recognised the benefits of deferred recruitment, but these did not translate into enhanced recruitment of participants. The model resulted in the loss of a third of children who were identified by the GP as eligible, but not subsequently recruited to the study. If the potential for improving outcomes in primary care through complex studies is to be realised, new approaches to recruitment into primary care trials need to be developed and evaluated. International Standard Randomised Controlled Trials, ISRCTN96705420 . Registered on 27 June 2012.

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.

Scoliosis and dental occlusion: a review of the literature

PubMed Central

2011-01-01

Background Idiopathic scoliosis is a deformity without clear etiology. It is unclear wether there is an association between malocclusion and scoliosis. Several types of occlusion were described in subjects with scoliosis, mostly case-reports. Objectives The aim of this review was to evaluate the type of occluslins more prevalent in subjects with scoliosis Search strategy All randomised and controlled clinical trials identified from the Cochrane Oral Health Group Trials Register, a MEDLINE search using the Mesh term scoliosis, malocclusion, and relevant free text words, and the bibliographies of papers and review articles which reported the outcome of orthodontic treatment in subjects with scoliosis that were published as abstracts or papers between 1970 and 2010. Selection criteria All randomised and controlled clinical trials published as full papers or abstracts which reported quantitative data on the outcomes malocclusion in subjects with scoliosis. Data collection and analysis Data were extracted without blinding to the authors, age of patients or type of occlusion. Main results Using the search strategy eleven observational longitudinal studies were identified. No randomized clinical trials were recorded. Twenty-three cross-sectional studies were recorderd, and the others studies were reviews, editorials, case-reports, or opinions. The clinical trials were often not controlled and were about the cephalometric evaluation after treatment with the modified Milwuakee brace, followed by the orthodontic treatment of the class II relationship with a functional appliance. Clinical trials also included the study of the associations between scoliosis and unilateral crossbite, in children with asymmetry of the upper cervical spine. This association was also investigated in rats, pigs and rabbits in clinical trials. The other associations between scoliosis and occlusion seems to be based only on cross-sectional studies, case-reports, opinions. Authors' conclusions Based on selected studies, this review concludes that there is plausible evidence for an increased prevalence of unilateral Angle Class II malocclusions associated with scoliosis, and an increased risk of lateral crossbite, midline deviation in children affected by scoliosis. Also, documentation of associations between reduced range of lateral movements and scoliosis seem convincing. Data are also mentioned about the association between plagiocephaly and scoliosis. PMID:21801357

Relationship between sponsorship and failure rate of dental implants: a systematic approach.

PubMed

Popelut, Antoine; Valet, Fabien; Fromentin, Olivier; Thomas, Aurélie; Bouchard, Philippe

2010-04-21

The number of dental implant treatments increases annually. Dental implants are manufactured by competing companies. Systematic reviews and meta-analysis have shown a clear association between pharmaceutical industry funding of clinical trials and pro-industry results. So far, the impact of industry sponsorship on the outcomes and conclusions of dental implant clinical trials has never been explored. The aim of the present study was to examine financial sponsorship of dental implant trials, and to evaluate whether research funding sources may affect the annual failure rate. A systematic approach was used to identify systematic reviews published between January 1993 and December 2008 that specifically deal with the length of survival of dental implants. Primary articles were extracted from these reviews. The failure rate of the dental implants included in the trials was calculated. Data on publication year, Impact Factor, prosthetic design, periodontal status reporting, number of dental implants included in the trials, methodological quality of the studies, presence of a statistical advisor, and financial sponsorship were extracted by two independent reviewers (kappa = 0.90; CI(95%) [0.77-1.00]). Univariate quasi-Poisson regression models and multivariate analysis were used to identify variables that were significantly associated with failure rates. Five systematic reviews were identified from which 41 analyzable trials were extracted. The mean annual failure rate estimate was 1.09%.(CI(95%) [0.84-1.42]). The funding source was not reported in 63% of the trials (26/41). Sixty-six percent of the trials were considered as having a risk of bias (27/41). Given study age, both industry associated (OR = 0.21; CI(95%) [0.12-0.38]) and unknown funding source trials (OR = 0.33; (CI(95%) [0.21-0.51]) had a lower annual failure rates compared with non-industry associated trials. A conflict of interest statement was disclosed in 2 trials. When controlling for other factors, the probability of annual failure for industry associated trials is significantly lower compared with non-industry associated trials. This bias may have significant implications on tooth extraction decision making, research on tooth preservation, and governmental health care policies.

Utilization of a Clinical Trial Management System for the Whole Clinical Trial Process as an Integrated Database: System Development

PubMed Central

Park, Yu Rang; Yoon, Young Jo; Koo, HaYeong; Yoo, Soyoung; Choi, Chang-Min; Beck, Sung-Ho

2018-01-01

Background Clinical trials pose potential risks in both communications and management due to the various stakeholders involved when performing clinical trials. The academic medical center has a responsibility and obligation to conduct and manage clinical trials while maintaining a sufficiently high level of quality, therefore it is necessary to build an information technology system to support standardized clinical trial processes and comply with relevant regulations. Objective The objective of the study was to address the challenges identified while performing clinical trials at an academic medical center, Asan Medical Center (AMC) in Korea, by developing and utilizing a clinical trial management system (CTMS) that complies with standardized processes from multiple departments or units, controlled vocabularies, security, and privacy regulations. Methods This study describes the methods, considerations, and recommendations for the development and utilization of the CTMS as a consolidated research database in an academic medical center. A task force was formed to define and standardize the clinical trial performance process at the site level. On the basis of the agreed standardized process, the CTMS was designed and developed as an all-in-one system complying with privacy and security regulations. Results In this study, the processes and standard mapped vocabularies of a clinical trial were established at the academic medical center. On the basis of these processes and vocabularies, a CTMS was built which interfaces with the existing trial systems such as the electronic institutional review board health information system, enterprise resource planning, and the barcode system. To protect patient data, the CTMS implements data governance and access rules, and excludes 21 personal health identifiers according to the Health Insurance Portability and Accountability Act (HIPAA) privacy rule and Korean privacy laws. Since December 2014, the CTMS has been successfully implemented and used by 881 internal and external users for managing 11,645 studies and 146,943 subjects. Conclusions The CTMS was introduced in the Asan Medical Center to manage the large amounts of data involved with clinical trial operations. Inter- and intraunit control of data and resources can be easily conducted through the CTMS system. To our knowledge, this is the first CTMS developed in-house at an academic medical center side which can enhance the efficiency of clinical trial management in compliance with privacy and security laws. PMID:29691212

Outcome of Non-Invasive Brain Stimulation in Substance Use Disorders: A Review of Randomized Sham-Controlled Clinical Trials.

PubMed

Trojak, Benoit; Sauvaget, Anne; Fecteau, Shirley; Lalanne, Laurence; Chauvet-Gelinier, Jean-Christophe; Koch, Sonja; Bulteau, Samuel; Zullino, Daniele; Achab, Sophia

2017-01-01

Non-invasive brain stimulation (NIBS) might be a new approach to treat substance use disorders (SUD). A systematic review and critical analysis was performed to identify potential therapeutic effects of NIBS on addictions. A search of the Medline database was conducted for randomized sham-controlled trials using NIBS in the field of addiction and published until August 2016. Twenty-six studies in various SUD met the inclusion criteria. Converging evidence indicates that NIBS might be a promising mean to treat patients with alcohol and tobacco use disorders, by acting on craving reduction and other mechanisms such as improvement in cognitive dysfunctions.

Pilates

PubMed Central

Di Lorenzo, Christine E.

2011-01-01

Context: The interest and popularity of Pilates is increasing worldwide. In addition to being used in fitness programs, it is being used in some rehabilitation programs. Evidence Acquisition: This review summarizes level III evidence from 1995 to 2009 obtained from PubMed (MEDLINE), CINAHL, and the Internet. Meta-analyses, systematic reviews, randomized controlled trials, and controlled trials published in peer-reviewed journals were retrieved for appraisal. The keywords searched were Pilates and core stabilization. Results: Ninety articles were identified in MEDLINE and CINAHL; 9 articles satisfied the inclusion criteria for level III evidence. Conclusion: There is a scientific basis for the effectiveness of Pilates exercise, with limited evidence to support it as a rehabilitative intervention. PMID:23016028

Hierarchy of evidence: differences in results between non-randomized studies and randomized trials in patients with femoral neck fractures.

PubMed

Bhandari, Mohit; Tornetta, Paul; Ellis, Thomas; Audige, Laurent; Sprague, Sheila; Kuo, Jonathann C; Swiontkowski, Marc F

2004-01-01

There have been a number of non-randomized studies comparing arthroplasty with internal fixation in patients with femoral neck fractures. However, there remains considerable debate about whether the results of non-randomized studies are consistent with the results of randomized, controlled trials. Given the economic burden of hip fractures, it remains essential to identify therapies to improve outcomes; however, whether data from non-randomized studies of an intervention should be used to guide patient care remains unclear. We aimed to determine whether the pooled results of mortality and revision surgery among non-randomized studies were similar to those of randomized trials in studies comparing arthroplasty with internal fixation in patients with femoral neck fractures. We conducted a Medline search from 1969 to June 2002, identifying both randomized and non-randomized studies comparing internal fixation with arthroplasty in patients with femoral neck fractures. Additional strategies to identify relevant articles included Cochrane database, SCISEARCH, textbooks, annual meeting programs, and content experts. We abstracted information on mortality and revision rates in each study and compared the pooled results between non-randomized and randomized studies. In addition, we explored potential reasons for dissimilar results between the two study designs. We identified 140 citations that addressed the general topic of comparison of arthroplasty and internal fixation for hip fracture. Of these, 27 studies met the eligibility criteria, 13 of which were non-randomized studies and 14 of which were randomized trials. Mortality data was available in all 13 non-randomized studies ( n=3108 patients) and in 12 randomized studies ( n=1767 patients). Non-randomized studies overestimated the risk of mortality by 40% when compared with the results of randomized trials (relative risk 1.44 vs 1.04, respectively). Information on revision risk was available in 9 non-randomized studies ( n=2764 patients) and all 14 randomized studies ( n=1901 patients). Both estimates from non-randomized and randomized studies revealed a significant reduction in the risk of revision surgery with arthroplasty compared with internal fixation (relative risk 0.38 vs 0.23, respectively). The reduction in the risk of revision surgery with arthroplasty compared with internal fixation was 62% for non-randomized studies and 77% for randomized trials. Thus, non-randomized studies underestimated the relative benefit of arthroplasty by 19.5%. Non-randomized studies with point estimates of relative risk similar to the pooled estimate for randomized trials all controlled for patient age, gender, and fracture displacement in their comparisons of mortality. We were unable to identify reasons for differences in the revision rate results between the study designs. Similar to other reports in medical subspecialties, non-randomized studies provided results dissimilar to randomized trials of arthroplasty vs internal fixation for mortality and revision rates in patients with femoral neck fractures. Investigators should be aware of these discrepancies when evaluating the merits of alternative surgical interventions, especially when both randomized trials and non-randomized comparative studies are available.

Iodixanol versus low-osmolar contrast media for prevention of contrast induced nephropathy: meta-analysis of randomized, controlled trials.

PubMed

From, Aaron M; Al Badarin, Firas J; McDonald, Furman S; Bartholmai, Brian J; Cha, Stephen S; Rihal, Charanjit S

2010-08-01

Contrast-induced nephropathy (CIN) is associated with significant morbidity and mortality. The objective of our meta-analysis was to assess the efficacy of iodixanol compared with low-osmolar contrast media (LOCM) for prevention of CIN. We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and internet sources of cardiology trial results for individual and relevant reviews of randomized, controlled trials, for the terms contrast media, contrast nephropathy, renal failure, iodixanol, Visipaque, and low-osmolar contrast media. All studies reported an incidence rate of CIN for each study group; there was no restriction on the definition of CIN. There were no restrictions on journal type or patient population. Overall, 36 trials were identified for analysis of aggregated summary data on 7166 patients; 3672 patients received iodixanol and 3494 patients received LOCM. Overall, iodixanol showed no statistically significant reduction in CIN incidence below that observed with heterogeneous comparator agents (P=0.11). Analysis of patient subgroups revealed that there was a significant benefit of iodixanol when compared with iohexol alone (odds ratio, 0.25; 95% confidence interval, 0.11 to 0.55; P<0.001) but not when compared with LOCM other than iohexol or with other ionic dimers or among patients receiving intra-arterial contrast injections or among patients undergoing coronary angiography with or without percutaneous intervention. Analysis of aggregated summary data from multiple randomized, controlled trials of iodixanol against diverse LOCMs for heterogeneous procedures and definitions of CIN show an iodixanol-associated reduction that is suggestive but statistically nonsignificant.

Renal denervation for the management of resistant hypertension

PubMed Central

Patel, Hitesh C; Hayward, Carl; Vassiliou, Vassilis; Patel, Ketna; Howard, James P; Di Mario, Carlo

2015-01-01

Renal sympathetic denervation (RSD) as a therapy for patients with resistant hypertension has attracted great interest. The majority of studies in this field have demonstrated impressive reductions in blood pressure (BP). However, these trials were not randomized or sham-controlled and hence, the findings may have been overinflated due to trial biases. SYMPLICITY HTN-3 was the first randomized controlled trial to use a blinded sham-control and ambulatory BP monitoring. A surprise to many was that this study was neutral. Possible reasons for this neutrality include the fact that RSD may not be effective at lowering BP in man, RSD was not performed adequately due to limited operator experience, patients’ adherence with their anti-hypertensive drugs may have changed during the trial period, and perhaps the intervention only works in certain subgroups that are yet to be identified. Future studies seeking to demonstrate efficacy of RSD should be designed as randomized blinded sham-controlled trials. The efficacy of RSD is in doubt, but many feel that its safety has been established through the thousands of patients in whom the procedure has been performed. Over 90% of these data, however, are for the Symplicity™ system and rarely extend beyond 12 months of follow-up. Long-term safety cannot be assumed with RSD and nor should it be assumed that if one catheter system is safe then all are. We hope that in the near future, with the benefit of well-designed clinical trials, the role of renal denervation in the management of hypertension will be established. PMID:26672761

Stroke prevention by cilostazol in patients with atherothrombosis: meta-analysis of placebo-controlled randomized trials.

PubMed

Uchiyama, Shinichiro; Demaerschalk, Bart M; Goto, Shinya; Shinohara, Yukito; Gotoh, Fumio; Stone, William M; Money, Samuel R; Kwon, Sun Uck

2009-01-01

Cilostazol is an antiplatelet agent that inhibits phosphodiesterase III in platelets and vascular endothelium. Previous randomized controlled trials of cilostazol for prevention of cerebrovascular events have garnered mixed results. We performed a systematic review and meta-analysis of the randomized clinical trials in patients with atherothrombotic diseases to determine the effects of cilostazol on cerebrovascular, cardiac, and all vascular events, and on all major hemorrhagic events. Relevant trials were identified by searching MEDLINE, EMBASE, and the Cochrane Controlled Trial Registry for titles and abstracts. Data from 12 randomized controlled trials, involving 5674 patients, were analyzed for end points of cerebrovascular, cardiac, and major bleeding events. Searching, determination of eligibility, data extraction, and meta-analyses were conducted by multiple independent investigators. Data were available in 3782, 1187, and 705 patients with peripheral arterial disease, cerebrovascular disease, and coronary stenting, respectively. Incidence of total vascular events was significantly lower in the cilostazol group compared with the placebo group (relative risk [RR], 0.86; 95% confidence interval [CI], 0.74-0.99; P=.038). This was particularly influenced by a significant decrease of incidence of cerebrovascular events in the cilostazol group (RR, 0.58; 95% CI, 0.43-0.78; P < .001). There was no significant intergroup difference in incidence of cardiac events (RR, 0.99; 95% CI, 0.83-1.17; P=.908) and serious bleeding complications (RR, 1.00; 95% CI, 0.66-1.51; P=.996). This first meta-analysis of cilostazol in patients with atherothrombosis demonstrated a significant risk reduction for cerebrovascular events, with no associated increase of bleeding risk.

Drug therapies for reducing gastric acidity in people with cystic fibrosis.

PubMed

Ng, Sze May; Francini, Angelo J

2012-04-18

Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use. 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, abstract books and conference proceedings.Most recent search of the Group's Trials Register: 15 February 2012. All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment. Both authors independently selected trials, assessed trial quality and extracted data. Thirty-eight trials were identified from the searches. Sixteen trials, with 256 participants, were suitable for inclusion. Seven trials were limited to children and three trials enrolled only adults. Meta-analysis was not performed. However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival. Trials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.

"I didn't really understand it, I just thought it'd help": exploring the motivations, understandings and experiences of patients with advanced lung cancer participating in a non-placebo clinical IMP trial.

PubMed

Harrop, Emily; Noble, Simon; Edwards, Michelle; Sivell, Stephanie; Moore, Barbara; Nelson, Annmarie

2016-07-20

Few studies have explored in depth the experiences of patients with advanced cancer who are participating in clinical investigational medicinal product trials. However, integrated qualitative studies in such trials are needed to enable a broader evaluation of patient experiences in the trial, with important ethical and practical implications for the design and conduct of similar trials and treatment regimes in the future. Ten participants were recruited from the control and intervention arms of FRAGMATIC: a non-placebo trial for patients with advanced lung cancer. Participants were interviewed at up to three time points during their time in the trial. Interviews were analysed using Interpretive Phenomenological Analysis. Patients were motivated to join the trial out of hope of medical benefit and altruism. Understanding of randomisation was mixed and in some cases poor, as was appreciation of trial purpose and equipoise. The trial was acceptable to and evaluated positively by most participants; participants receiving the intervention focused on the potential treatment benefits they hoped they would receive, whilst participants in the control arm found alternative reasons, such as altruism, personal fulfilment and positive attention, to commit to and perceive benefits from the trial. However, whilst experiences were generally very positive, poor understanding, limited engagement with trial information and focus on treatment benefits amongst some participants give cause for concern. By exploring longitudinally the psychological, emotional and cognitive domains of trial participation, we consider potential harms and benefits of participation in non-placebo trials amongst patients with advanced lung cancer and identify several implications for future research with and care for patients with advanced cancer. ISRCTN80812769 . Registered on 8 July 2005.

Reporting of Randomized Trials in Common Cancers in the Lay Media.

PubMed

Ribnikar, Domen; Goldvaser, Hadar; Ocana, Alberto; Templeton, Arnoud J; Seruga, Bostjan; Amir, Eitan

2018-01-01

Limited data exist about the role of the lay media in the dissemination of results of randomized controlled trials (RCTs) in common cancers. Completed phase III RCTs evaluating new drugs in common cancers between January 2005 and October 2016 were identified from ClinicalTrials.gov. Lay media reporting was identified by searching LexisNexis Academic. Scientific reporting was defined as presentation at an academic conference or publication in full. Associations between reporting in the lay media before scientific reporting and study design and sponsorship were evaluated using logistic regression. Of 180 RCTs identified, 52% were reported in the lay media and in 27%, lay media reporting occurred before scientific reporting with an increasing trend over time (p = 0.009). Reporting in the lay media before scientific reporting was associated with positive results (OR: 2.10, p = 0.04), targeted therapy compared to chemotherapy (OR: 4.75, p = 0.006), immunotherapy compared to chemotherapy (OR: 7.60, p = 0.02), and prostate cancer compared to breast cancer (OR: 3.25, p = 0.02). Over a quarter of all RCTs in common cancers are reported in the lay media before they are reported scientifically with an increasing proportion over time. Positive trials, studies in prostate cancer, and trials of immunotherapy are associated with early reporting in the lay media. © 2017 S. Karger AG, Basel.

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol

PubMed Central

2012-01-01

Background Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. Methods/Design We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Discussion Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. Trial registration Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18. PMID:22305183

Vitamin D status and weight loss: a systematic review and meta-analysis of randomized and nonrandomized controlled weight-loss trials.

PubMed

Mallard, Simonette R; Howe, Anna S; Houghton, Lisa A

2016-10-01

Obesity is associated with lower concentrations of serum 25-hydroxyvitamin D; however, uncertainty exists as to the direction of causation. To date, meta-analyses of randomized controlled vitamin D-supplementation trials have shown no effect of raising circulating vitamin D on body weight, although several weight-loss-intervention trials have reported an increase in circulating vitamin D after weight reduction. We undertook a systematic review and meta-analysis of randomized and nonrandomized controlled trials to determine whether weight loss compared with weight maintenance leads to an increase in serum 25-hydroxyvitamin D. A systematic search for controlled weight-loss-intervention studies published up to 31 March 2016 was performed. Studies that included participants of any age with changes in adiposity and serum 25-hydroxyvitamin D as primary or secondary outcomes were considered eligible. We identified 4 randomized controlled trials (n = 2554) and 11 nonrandomized controlled trials (n = 917) for inclusion in the meta-analysis. Random assignment to weight loss compared with weight maintenance resulted in a greater increase in serum 25-hydroxyvitamin D with a mean difference of 3.11 nmol/L (95% CI: 1.38, 4.84 nmol/L) between groups, whereas a mean difference of 4.85 nmol/L (95% CI: 2.59, 7.12 nmol/L) was observed in nonrandomized trials. No evidence for a dose-response effect of weight loss on the change in serum 25-hydroxyvitamin D was shown overall. Our results indicate that vitamin D status may be marginally improved with weight loss in comparison with weight maintenance under similar conditions of supplemental vitamin D intake. Although additional studies in unsupplemented individuals are needed to confirm these findings, our results support the view that the association between obesity and lower serum 25-hydroxyvitamin D may be due to reversed causation with increased adiposity leading to suboptimal concentrations of circulating vitamin D. This trial was registered at www.crd.york.ac.uk/PROSPERO/ as CRD42015023836. © 2016 American Society for Nutrition.

Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials

PubMed Central

Gilbert, Peter B.; Juraska, Michal; deCamp, Allan C.; Karuna, Shelly; Edupuganti, Srilatha; Mgodi, Nyaradzo; Donnell, Deborah J.; Bentley, Carter; Sista, Nirupama; Andrew, Philip; Isaacs, Abby; Huang, Yunda; Zhang, Lily; Capparelli, Edmund; Kochar, Nidhi; Wang, Jing; Eshleman, Susan H.; Mayer, Kenneth H.; Magaret, Craig A.; Hural, John; Kublin, James G.; Gray, Glenda; Montefiori, David C.; Gomez, Margarita M.; Burns, David N.; McElrath, Julie; Ledgerwood, Julie; Graham, Barney S.; Mascola, John R.; Cohen, Myron; Corey, Lawrence

2017-01-01

Background Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. Methods The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial is designed (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection. Results Each AMP trial is designed to have 90% power to detect PE > 0% if PE is ≥ 60%. The AMP trials are also designed to identify VRC01 properties (i.e., concentration and effector functions) that correlate with protection and to provide insight into mechanistic CoPs. CoPs are assessed using data from breakthrough HIV-1 infections, including genetic sequences and sensitivities to VRC01-mediated neutralization and Fc effector functions. Conclusions The AMP trials test whether VRC01 can prevent HIV-1 infection in two study populations. If affirmative, they will provide information for estimating the optimal dosage of VRC01 (or subsequent derivatives) and identify threshold levels of neutralization and Fc effector functions associated with high-level protection, setting a benchmark for future vaccine evaluation and constituting a bridge to other bnAb approaches for HIV-1 prevention. PMID:29218117

Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials.

PubMed

Gilbert, Peter B; Juraska, Michal; deCamp, Allan C; Karuna, Shelly; Edupuganti, Srilatha; Mgodi, Nyaradzo; Donnell, Deborah J; Bentley, Carter; Sista, Nirupama; Andrew, Philip; Isaacs, Abby; Huang, Yunda; Zhang, Lily; Capparelli, Edmund; Kochar, Nidhi; Wang, Jing; Eshleman, Susan H; Mayer, Kenneth H; Magaret, Craig A; Hural, John; Kublin, James G; Gray, Glenda; Montefiori, David C; Gomez, Margarita M; Burns, David N; McElrath, Julie; Ledgerwood, Julie; Graham, Barney S; Mascola, John R; Cohen, Myron; Corey, Lawrence

2017-01-01

Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial is designed (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection. Each AMP trial is designed to have 90% power to detect PE > 0% if PE is ≥ 60%. The AMP trials are also designed to identify VRC01 properties (i.e., concentration and effector functions) that correlate with protection and to provide insight into mechanistic CoPs. CoPs are assessed using data from breakthrough HIV-1 infections, including genetic sequences and sensitivities to VRC01-mediated neutralization and Fc effector functions. The AMP trials test whether VRC01 can prevent HIV-1 infection in two study populations. If affirmative, they will provide information for estimating the optimal dosage of VRC01 (or subsequent derivatives) and identify threshold levels of neutralization and Fc effector functions associated with high-level protection, setting a benchmark for future vaccine evaluation and constituting a bridge to other bnAb approaches for HIV-1 prevention.

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.

Design of a cluster-randomized minority recruitment trial: RECRUIT.

PubMed

Tilley, Barbara C; Mainous, Arch G; Smith, Daniel W; McKee, M Diane; Amorrortu, Rossybelle P; Alvidrez, Jennifer; Diaz, Vanessa; Ford, Marvella E; Fernandez, Maria E; Hauser, Robert A; Singer, Carlos; Landa, Veronica; Trevino, Aron; DeSantis, Stacia M; Zhang, Yefei; Daniels, Elvan; Tabor, Derrick; Vernon, Sally W

2017-06-01

Racial/ethnic minority groups remain underrepresented in clinical trials. Many strategies to increase minority recruitment focus on minority communities and emphasize common diseases such as hypertension. Scant literature focuses on minority recruitment to trials of less common conditions, often conducted in specialty clinics and dependent on physician referrals. We identified trust/mistrust of specialist physician investigators and institutions conducting medical research and consequent participant reluctance to participate in clinical trials as key-shared barriers across racial/ethnic groups. We developed a trust-based continuous quality improvement intervention to build trust between specialist physician investigators and community minority-serving physicians and ultimately potential trial participants. To avoid the inherent biases of non-randomized studies, we evaluated the intervention in the national Randomized Recruitment Intervention Trial (RECRUIT). This report presents the design of RECRUIT. Specialty clinic follow-up continues through April 2017. We hypothesized that specialist physician investigators and coordinators trained in the trust-based continuous quality improvement intervention would enroll a greater proportion of minority participants in their specialty clinics than specialist physician investigators in control specialty clinics. Specialty clinic was the unit of randomization. Using continuous quality improvement, the specialist physician investigators and coordinators tailored recruitment approaches to their specialty clinic characteristics and populations. Primary analyses were adjusted for clustering by specialty clinic within parent trial and matching covariates. RECRUIT was implemented in four multi-site clinical trials (parent trials) supported by three National Institutes of Health institutes and included 50 associated specialty clinics from these parent trials. Using current data, we have 88% power or greater to detect a 0.15 or greater difference from the currently observed control proportion adjusting for clustering. We detected no differences in baseline matching criteria between intervention and control specialty clinics (all p values > 0.17). RECRUIT was the first multi-site randomized control trial to examine the effectiveness of a trust-based continuous quality improvement intervention to increase minority recruitment into clinical trials. RECRUIT's innovations included its focus on building trust between specialist investigators and minority-serving physicians, the use of continuous quality improvement to tailor the intervention to each specialty clinic's specific racial/ethnic populations and barriers to minority recruitment, and the use of specialty clinics from more than one parent multi-site trial to increase generalizability. The effectiveness of the RECRUIT intervention will be determined after the completion of trial data collection and planned analyses.

The rate of decline of joint space width in patients with osteoarthritis of the knee: a systematic review and meta-analysis of randomized placebo-controlled trials of chondroitin sulfate .

PubMed

Hochberg, Marc C; Zhan, Min; Langenberg, Patricia

2008-11-01

Chondroitin sulfate has been shown to relieve pain and improve functional limitation in patients with osteoarthritis (OA) of the knee in numerous clinical trials and meta-analyses. Its role as a potential structure-modifying drug for knee OA, however, remains controversial. To perform a meta-analysis of randomized double-blind placebo-controlled clinical trials to assess the efficacy of chondroitin sulfate as a structure-modifying drug for knee OA. A Medline search was conducted from 1996 through 2007 and five articles that reported results from three trials were identified; one additional trial was identified through review of presentations at annual rheumatology meetings. There was no evidence of heterogeneity across the trials and results were pooled using a fixed effects meta-analysis. Pooled results demonstrated a small significant effect of chondroitin sulfate on the reduction in rate of decline in minimum joint space width of 0.07 mm/year (95% CI 0.03, 0.10) that corresponded to an effect size of 0.26 (95% CI 0.14, 0.38) (p < 0.0001). This result was robust in sensitivity analyses. The individual studies included in the meta-analysis varied in the number of patients enrolled and the techniques used to acquire knee radiographs and to measure joint space width. These results demonstrate that chondroitin sulfate is effective for reducing the rate of decline in minimum joint space width in patients with OA of the knee. Chondroitin sulfate may have a role as a structure-modifying agent in the management of patients with knee OA.

Top-Down Prioritization of Salient Items May Produce the So-Called Stimulus-Driven Capture

PubMed Central

Benoni, Hanna

2018-01-01

The current study proposes that top-down attentional prioritization of salient items may produce the so-called stimulus-driven capture. To test this proposal, the “expectation-based paradigm” was designed on the basis of a visual search task. In Experiment 1, a task-irrelevant singleton frame was presented at the same location in 70% of the trials. The target was either presented at chance level within the singleton location, or away from it. In line with the singleton capture phenomenon, participants were faster in identifying the target when it appeared in the singleton location compared to non-singleton locations. However, leaving out the singleton frame in 30% of the trials led to a similar effect; participants were faster in identifying the target when it appeared in the expected singleton location compared to expected non-singletons locations (a “quasi-capture” effect). These results suggest that the participants allocated their attention to the expected singleton location, rather than that the singleton itself captured attention. In Experiment 2, the same task-irrelevant color singleton was presented in a random position in 70% of the trials. This color frame was shown as a non-singleton in all of the 30% singleton-absent multicolored trials. A similar facilitation effect was obtained when the target appeared in the expected singleton color frame compared to other frames, in singleton-absent trials as in singleton-present trials. These results further support the idea that instances of singleton capture can be explained by top-down attentional shifts toward singleton items. Theoretical implications of these results are discussed. Mostly, the study calls to consider the possibility that all sources of attentional control may be represented by a continuous variable of top-down control, including the category of “physical salience.” PMID:29599731