Testing a Violence-Prevention Intervention for Incarcerated Women Using a Randomized Control Trial

ERIC Educational Resources Information Center

Kubiak, Sheryl Pimlott; Kim, Woo Jong; Fedock, Gina; Bybee, Deborah

2015-01-01

Objective: Beyond Violence (BV), a new prevention program for women with assaultive offenses, demonstrated feasibility in previous studies. This study's purpose is to assess the efficacy of BV using a randomized control trial. Method: Eligible women were randomly assigned to treatment as usual (TAU) and the experimental condition (BV). Measures of…

Efficacy of a Universal Parent Training Program (HOPE-20): Cluster Randomized Controlled Trial

ERIC Educational Resources Information Center

Leung, Cynthia; Tsang, Sandra; Kwan, H. W.

2017-01-01

Objective: This study examined the efficacy of Hands-On Parent Empowerment-20 (HOPE-20) program. Methods: Eligible participants were parents residing in Hong Kong with target children aged 2 years attending nursery schools. Cluster randomized control trial was adopted, with 10 schools (110 participants) assigned to intervention group and 8 schools…

ACT2 peer-driven intervention increases enrollment into HIV/AIDS medical studies among African-Americans/Blacks and Hispanics: A cluster randomized controlled trial

PubMed Central

Gwadz, Marya; Cleland, Charles M.; Belkin, Mindy; Ritchie, Amanda; Leonard, Noelle; Riedel, Marion; Banfield, Angela; Colon, Pablo; Elharrar, Vanessa; Kagan, Jonathan; Mildvan, Donna

2014-01-01

African American/Black and Hispanic persons living with HIV/AIDS (“AABH-PLHA”) are under-represented in HIV/AIDS medical studies (HAMS). This paper evaluates the efficacy of a social/behavioral intervention to increase rates of screening for and enrollment into HAMS in these populations. Participants (N=540) were enrolled into a cluster randomized controlled trial of an intervention designed to overcome multi-level barriers to HAMS. Primary endpoints were rates of screening for and enrollment into therapeutic/treatment-oriented and observational studies. Intervention arm participants were 30 times more likely to be screened than controls (49.3% vs. 3.7%; p < .001). Half (55.5%) of those screened were eligible for HAMS, primarily observational studies. Nine out of ten found eligible enrolled (91.7%), almost all into observational studies (95.2%), compared to no enrollments among controls. Achieving appropriate representation of AABH-PLHA in HAMS necessitates modification of study inclusion criteria to increase the proportion found eligible for therapeutic HAMS, in addition to social/behavioral interventions. PMID:24961193

Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials

PubMed Central

Forman, David; Hunt, Richard H; Yuan, Yuhong; Moayyedi, Paul

2014-01-01

Objectives To determine whether searching for Helicobacter pylori and treating with eradication therapy leads to a reduction in incidence of gastric cancer among healthy asymptomatic infected individuals. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, and the Cochrane central register of controlled trials were searched through to December 2013. Conference proceedings between 2001 and 2013 were hand searched. A recursive search was performed with bibliographies of relevant studies. There were no language restrictions. Eligibility criteria for selecting studies Randomised controlled trials examining the effect of at least seven days of eradication therapy on subsequent occurrence of gastric cancer in adults who tested positive for Helicobacter pylori but otherwise healthy and asymptomatic were eligible. The control arm had to receive placebo or no treatment. Subjects had to be followed for ≥2 years. Main outcome measures Primary outcome, defined a priori, was the effect of eradication therapy on the subsequent occurrence of gastric cancer expressed as a relative risk of gastric cancer with 95% confidence intervals. Results The search strategy identified 1560 citations, of which six individual randomised controlled trials were eligible. Fifty one (1.6%) gastric cancers occurred among 3294 individuals who received eradication therapy versus 76 (2.4%) in 3203 control subjects (relative risk 0.66, 95% confidence interval 0.46 to 0.95), with no heterogeneity between studies (I2=0%, P=0.60). If the benefit of eradication therapy was assumed to persist lifelong the number needed to treat was as low as 15 for Chinese men and as high as 245 for US women. Conclusions These data provide limited, moderate quality evidence that searching for and eradicating H pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but these data cannot necessarily be extrapolated to other populations. PMID:24846275

Evaluation of eligibility and recruitment in breast cancer clinical trials.

PubMed

Lemieux, Julie; Forget, Geneviève; Brochu, Olyvia; Provencher, Louise; Cantin, Guy; Desbiens, Christine; Doyle, Catherine; Poirier, Brigitte; Camden, Stéphanie; Durocher, Martin

2014-08-01

Objectives of the study were to measure recruitment rates in clinical trials and to identify patients, physicians or trials characteristics associated with higher recruitment rates. Among patients who had a clinical trial available for their cancer, 83.5% (345/413) met the eligibility criteria to at least one clinical trial. At least one trial was proposed to 33.1% (113/341) of the eligible patients and 19.7% (68/345) were recruited. Overall recruitment was 16.5% (68/413). In multivariate analyses, trial proposal and enrollment were lower for elderly patients and higher in high cancer stages. Trials from pharmaceutical industry had higher recruitment rates and trials testing hormonal therapy enrolled more patients. Breast cancer patients' accrual to a clinical trial could be improved by trying to systematically identify all eligible patients and propose a trial to those eligible and to whom the treatment is planned to be equivalent to the standard arm of the trial. Copyright © 2014 Elsevier Ltd. All rights reserved.

Characteristics and Medication Use of Psoriasis Patients Who May or May Not Qualify for Randomized Controlled Trials.

PubMed

Malatestinic, William; Nordstrom, Beth; Wu, Jashin J; Goldblum, Orin; Solotkin, Kathleen; Lin, Chen-Yen; Kistler, Kristin; Fraeman, Kathy; Johnston, Joseph; Hawley, Lcdr Lesley; Sicignano, Nicholas; Araujo, Andre

2017-03-01

Clinical trials impose exclusion criteria that may limit the generalizability of results. To (a) determine the percentage of real-world patients who would qualify for psoriasis randomized controlled trials; (b) ascertain differences between moderate-to-severe psoriasis patients who would be eligible, ineligible, or potentially eligible for clinical trials; and (c) compare their biologic treatment patterns. Moderate-to-severe psoriasis patients were identified from the U.S. Department of Defense health care database from January 1, 2008, to October 31, 2013. Eligibility classification for psoriasis trials was based on common trial exclusion criteria involving medical conditions and recent treatment history. Patient characteristics and treatment patterns of 4 biologics (adalimumab, etanercept, infliximab, and ustekinumab) were compared between groups. Adherence was measured by medication possession ratio and persistence as continuous time on drug with ≤ 90-day gap between supply times. Among 16,284 qualifying psoriasis patients, 4,677 (28.7%) were medically ineligible, and 8,466 (52.0%) had ineligibility-related treatments that could be stopped prior to trial entry; the latter patients were considered potentially eligible for psoriasis trials. Common reasons for medical ineligibility included malignancies and hematologic disorders; treatment ineligibilities included use of topical corticosteroids and phototherapy. Medically ineligible patients were older and had more comorbidities, while potentially eligible patients were younger and healthier than trial-eligible patients. Most treatment patterns were similar across groups, except that, compared with the trial-eligible group, medically ineligible patients had greater adherence to infliximab and potentially trial-eligible patients had greater adherence and persistence to adalimumab. This large real-world study found that patients who may be ineligible for psoriasis trials differ in important respects (e.g., comorbidities, prior treatments) from their trial-eligible counterparts. Regardless of their differences at baseline, adherence, persistence, and switching of biologic medications are largely similar, with few differences noted among groups. Financial support for this study was provided by Lilly USA. Wu has received research funding from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Coherus Biosciences, Dermira, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Regeneron, Sandoz, and Sun Pharmaceutical Industries, and he is a consultant for AbbVie, Amgen, Celgene, Dermira, Eli Lilly, Pfizer, Regeneron, and Sun Pharmaceutical Industries. Malatestinic, Goldblum, Solotkin, Lin, Johnston, and Araujo are employees and/or stock owners of Lilly. Nordstrom, Kistler, and Fraeman are employees of Evidera, which received funding from Lilly to conduct this study. LCDR Hawley is a military service member. This work was prepared as part of her official duties. Title 17 U.S.C. 105 provides that "copyright protection under this title is not available for any work of the United States Government." Title 17 U.S.C. 101 defines a U.S. government work as a work prepared by a military service member or employee of the U.S. government as part of that person's official duties. Research data were derived from an approved Naval Medical Center, Portsmouth, Virginia, institutional review board protocol. The views expressed in this work are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the U.S. government. Study concept and design were contributed by Malatestinic and Araujo, along with the other authors. Nordstrom, Kistler, Fraeman, and Sicignano collected the data, and data interpretation was performed by Wu, Lin, and Hawley, along with Malatestinic, Nordstrom, Solotkin, and Araujo. The manuscript was written by Johnston, Malatestinic, Kistler, Wu, and Araujo, along with Nordstrom, Goldblum, Solotkin, Hawley, and Sicignano, and revised by Goldblum, Solotkin, Malatestinic, and Araujo, along with Nordstrom, Wu, Fraeman, Johnston, Hawley, and Sicignano.

Management of haemothoraces in blunt thoracic trauma: study protocol for a randomised controlled trial

PubMed Central

Carver, David A; Bressan, Alexsander K; Schieman, Colin; Grondin, Sean C; Kirkpatrick, Andrew W; Lall, Rohan; McBeth, Paul B; Dunham, Michael B; Ball, Chad G

2018-01-01

Introduction Haemothorax following blunt thoracic trauma is a common source of morbidity and mortality. The optimal management of moderate to large haemothoraces has yet to be defined. Observational data have suggested that expectant management may be an appropriate strategy in stable patients. This study aims to compare the outcomes of patients with haemothoraces following blunt thoracic trauma treated with either chest drainage or expectant management. Methods and analysis This is a single-centre, dual-arm randomised controlled trial. Patients presenting with a moderate to large sized haemothorax following blunt thoracic trauma will be assessed for eligibility. Eligible patients will then undergo an informed consent process followed by randomisation to either (1) chest drainage (tube thoracostomy) or (2) expectant management. These groups will be compared for the rate of additional thoracic interventions, major thoracic complications, length of stay and mortality. Ethics and dissemination This study has been approved by the institution’s research ethics board and registered with ClinicalTrials.gov. All eligible participants will provide informed consent prior to randomisation. The results of this study may provide guidance in an area where there remains significant variation between clinicians. The results of this study will be published in peer-reviewed journals and presented at national and international conferences. Trial registration number NCT03050502. PMID:29502092

Experience Corps: A dual trial to promote the health of older adults and children's academic success

PubMed Central

Fried, Linda P.; Carlson, Michelle C.; McGill, Sylvia; Seeman, Teresa; Xue, Qian-Li; Frick, Kevin; Tan, Erwin; Tanner, Elizabeth K.; Barron, Jeremy; Frangakis, Constantine; Piferi, Rachel; Martinez, Iveris; Gruenewald, Tara; Martin, Barbara K.; Berry-Vaughn, Laprisha; Stewart, John; Dickersin, Kay; Willging, Paul R.; Rebok, George W.

2014-01-01

Background As the population ages, older adults are seeking meaningful, and impactful, post-retirement roles. As a society, improving the health of people throughout longer lives is a major public health goal. This paper presents the design and rationale for an effectiveness trial of Experience Corps™, an intervention created to address both these needs. This trial evaluates (1) whether senior volunteer roles within Experience Corps™ beneficially impact children's academic achievement and classroom behavior in public elementary schools and (2) impact on the health of volunteers. Methods Dual evaluations of (1) an intention-to-treat trial randomizing eligible adults 60 and older to volunteer service in Experience Corps™, or to a control arm of usual volunteering opportunities, and (2) a comparison of eligible public elementary schools receiving Experience Corps™ to matched, eligible control schools in a 1:1 control:intervention school ratio. Outcomes For older adults, the primary outcome is decreased disability in mobility and Instrumental Activities of Daily Living (IADL). Secondary outcomes are decreased frailty, falls, and memory loss; slowed loss of strength, balance, walking speed, cortical plasticity, and executive function; objective performance of IADLs; and increased social and psychological engagement. For children, primary outcomes are improved reading achievement and classroom behavior in Kindergarten through the 3rd grade; secondary outcomes are improvements in school climate, teacher morale and retention, and teacher perceptions of older adults. Summary This trial incorporates principles and practices of community-based participatory research and evaluates the dual benefit of a single intervention, versus usual opportunities, for two generations: older adults and children. PMID:23680986

Reasons for non-recruitment of eligible patients to a randomised controlled trial of secondary prevention after intracerebral haemorrhage: observational study.

PubMed

Maxwell, Amy E; MacLeod, Mary Joan; Joyson, Anu; Johnson, Sharon; Ramadan, Hawraman; Bellfield, Ruth; Byrne, Anthony; McGhee, Caroline; Rudd, Anthony; Price, Fiona; Vasileiadis, Evangelos; Holden, Melinda; Hewitt, Jonathan; Carpenter, Michael; Needle, Ann; Valentine, Stacey; Patel, Farzana; Harrington, Frances; Mudd, Paul; Emsley, Hedley; Gregary, Bindu; Kane, Ingrid; Muir, Keith; Tiwari, Divya; Owusu-Agyei, Peter; Temple, Natalie; Sekaran, Lakshmanan; Ragab, Suzanne; England, Timothy; Hedstrom, Amanda; Jones, Phil; Jones, Sarah; Doherty, Mandy; McCarron, Mark O; Cohen, David L; Tysoe, Sharon; Al-Shahi Salman, Rustam

2017-04-05

Recruitment to randomised prevention trials is challenging, not least for intracerebral haemorrhage (ICH) associated with antithrombotic drug use. We investigated reasons for not recruiting apparently eligible patients at hospital sites that keep screening logs in the ongoing REstart or STop Antithrombotics Randomised Trial (RESTART), which seeks to determine whether to start antiplatelet drugs after ICH. By the end of May 2015, 158 participants had been recruited at 108 active sites in RESTART. The trial coordinating centre invited all sites that kept screening logs to submit screening log data, followed by one reminder. We checked the integrity of data, focused on the completeness of data about potentially eligible patients and categorised the reasons they were not randomised. Of 108 active sites, 39 (36%) provided usable screening log data over a median of ten (interquartile range = 5-13) months of recruitment per site. During this time, sites screened 633 potentially eligible patients and randomised 53 (8%) of them. The main reasons why 580 patients were not randomised were: 43 (7%) patients started anticoagulation, 51 (9%) patients declined, 148 (26%) patients' stroke physicians were not uncertain about using antiplatelet drugs, 162 (28%) patients were too unwell and 176 (30%) patients were not randomised due to other reasons. RESTART recruited ~8% of eligible patients. If more physicians were uncertain about the therapeutic dilemma that RESTART is addressing, RESTART could have recruited up to four times as many participants. The trial coordinating centre continues to engage with physicians about their uncertainty. EU Clinical Trials, EudraCT 2012-003190-26 . Registered on 3 July 2012.

Immediate chest X-ray for patients at risk of lung cancer presenting in primary care: randomised controlled feasibility trial

PubMed Central

Neal, Richard D; Barham, Allan; Bongard, Emily; Edwards, Rhiannon Tudor; Fitzgibbon, Jim; Griffiths, Gareth; Hamilton, Willie; Hood, Kerenza; Nelson, Annmarie; Parker, David; Porter, Cath; Prout, Hayley; Roberts, Kirsty; Rogers, Trevor; Thomas-Jones, Emma; Tod, Angela; Yeo, Seow Tien; Hurt, Chris N

2017-01-01

Background: Achieving earlier stage diagnosis is one option for improving lung cancer outcomes in the United Kingdom. Patients with lung cancer typically present with symptoms to general practitioners several times before referral or investigation. Methods: We undertook a mixed methods feasibility individually randomised controlled trial (the ELCID trial) to assess the feasibility and inform the design of a definitive, fully powered, UK-wide, Phase III trial of lowering the threshold for urgent investigation of suspected lung cancer. Patients over 60, with a smoking history, presenting with new chest symptoms to primary care, were eligible to be randomised to intervention (urgent chest X-ray) or usual care. Results: The trial design and materials were acceptable to GPs and patients. We randomised 255 patients from 22 practices, although the proportion of eligible patients who participated was lower than expected. Survey responses (89%), and the fidelity of the intervention (82% patients X-rayed within 3 weeks) were good. There was slightly higher anxiety and depression in the control arm in participants aged >75. Three patients (1.2%) were diagnosed with lung cancer. Conclusions: We have demonstrated the feasibility of individually randomising patients at higher risk of lung cancer, to a trial offering urgent investigation or usual care. PMID:28072761

Remedial after-school support classes offered in rural Gambia (The SCORE trial): study protocol for a cluster randomized controlled trial.

PubMed

Boone, Peter; Camara, Alpha; Eble, Alex; Elbourne, Diana; Fernandes, Samory; Frost, Chris; Jayanty, Chitra; Lenin, Maitri; Silva, Ana Filipa

2015-12-16

Low education levels are endemic in much of the developing world, particularly in rural areas where traditional government-provided public services often have difficulty reaching beneficiaries. Providing trained para-teachers to teach regular after-school remedial education classes has been shown to improve literacy and numeracy in children of primary school age residing in such areas in India. This trial investigates whether such an intervention can also be effective in a West African setting with similarly low learning levels and difficult geographic access. cluster-randomized controlled trial. Clusters: villages or groups of villages with 15-300 households and at least 15 eligible children in the Lower River and North Bank Regions of The Gambia. children born between 1 September 2007 and 31 August 2009 planning to enter the first grade, for the first time, in the 2015-2016 school year in eligible villages. We anticipate enrolling approximately 150 clusters of villages with approximately 6000 children as participants. a program providing remedial after-school lessons, focusing on literacy and numeracy, 5 to 6 days a week for 3 years to eligible children, based on the intervention evaluated in the Support To Rural India's Public Education System (STRIPES) trial (PLoS ONE 8(7):e65775). both the intervention and control groups will receive small bundles of useful materials during annual data collection as recompense for their time. If the education intervention is shown to be cost-effective at raising learning levels, it is expected that the control group villages will receive the intervention for several years after the trial results are available. the primary outcome of the trial is a composite mathematics and language test score. Secondary outcomes include school attendance, enrollment, performance on nationally administered exams, parents' spending on education, spillover learning to siblings and family members, and school-related time use of parents and children. Subgroup analyses of the primary outcome will also be carried out based on ethnic group, gender, distance from the main highway, parents' education level, and school type. The trial will run by independent research and implementation teams and supervised by a Trial Steering Committee. Along with the overall impact of the intervention, we will conduct a cost-effectiveness analysis. There are no major ethical issues for this study. Current controlled trials ISRCTN12500245 . 1 May 2015.

Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) post-natal intervention: an update to the study protocol for a randomized controlled trial.

PubMed

Shih, Sophy T F; Davis-Lameloise, Nathalie; Janus, Edward D; Wildey, Carol; Versace, Vincent L; Hagger, Virginia; Asproloupos, Dino; O'Reilly, Sharleen L; Phillips, Paddy A; Ackland, Michael; Skinner, Timothy; Oats, Jeremy; Carter, Rob; Best, James D; Dunbar, James A

2014-06-30

The Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) is a randomized controlled trial (RCT) that aims to assess the effectiveness of a structured diabetes prevention intervention for women who had gestational diabetes. The original protocol was published in Trials (http://www.trialsjournal.com/content/14/1/339). This update reports on an additional exclusion criterion and change in first eligibility screening to provide greater clarity. The new exclusion criterion "surgical or medical intervention to treat obesity" has been added to the original protocol. The risks of developing diabetes will be affected by any medical or surgical intervention as its impact on obesity will alter the outcomes being assessed by MAGDA-DPP. The screening procedures have also been updated to reflect the current recruitment operation. The first eligibility screening is now taking place either during or after pregnancy, depending on recruitment strategy. Australian New Zealand Clinical Trials Registry ANZCTRN 12610000338066.

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

Design and End Points of Clinical Trials for Patients With Progressive Prostate Cancer and Castrate Levels of Testosterone: Recommendations of the Prostate Cancer Clinical Trials Working Group

PubMed Central

Scher, Howard I.; Halabi, Susan; Tannock, Ian; Morris, Michael; Sternberg, Cora N.; Carducci, Michael A.; Eisenberger, Mario A.; Higano, Celestia; Bubley, Glenn J.; Dreicer, Robert; Petrylak, Daniel; Kantoff, Philip; Basch, Ethan; Kelly, William Kevin; Figg, William D.; Small, Eric J.; Beer, Tomasz M.; Wilding, George; Martin, Alison; Hussain, Maha

2014-01-01

Purpose To update eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone. Methods A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by reviewing previous criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and emerging trial data. Results The Prostate Cancer Clinical Trials Working Group (PCWG2) recommends a two-objective paradigm: (1) controlling, relieving, or eliminating disease manifestations that are present when treatment is initiated and (2) preventing or delaying disease manifestations expected to occur. Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory. Eligibility is defined using standard disease assessments to authenticate disease progression, prior treatment, distinct clinical subtypes, and predictive models. Outcomes are reported independently for prostate-specific antigen (PSA), imaging, and clinical measures, avoiding grouped categorizations such as complete or partial response. In most trials, early changes in PSA and/or pain are not acted on without other evidence of disease progression, and treatment should be continued for at least 12 weeks to ensure adequate drug exposure. Bone scans are reported as “new lesions” or “no new lesions,” changes in soft-tissue disease assessed by RECIST, and pain using validated scales. Defining eligibility for prevent/delay end points requires attention to estimated event frequency and/or random assignment to a control group. Conclusion PCWG2 recommends increasing emphasis on time-to-event end points (ie, failure to progress) as decision aids in proceeding from phase II to phase III trials. Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit. PMID:18309951

Generalizability of clinical trials of advanced melanoma in the real-world, population-based setting.

PubMed

Sam, Davis; Gresham, Gillian; Abdel-Rahman, Omar; Cheung, Winson Y

2018-06-18

Results from novel therapeutics trials are not always generalizable to real-world patients. We aimed to determine the pattern in which trial findings are applied in a population-based setting of melanoma patients and consequent treatment outcomes. Patients with unresectable disease during 2011-2014 and referred to cancer centers in a large Canadian province were retrospectively reviewed. Based on eligibility criteria as described in registration trials of vemurafenib (Vem) and ipilimumab (Ipi), we classified patients into trial-eligible and ineligible and those treated and untreated with these agents. We identified 290 patients with known BRAF status for the Vem analysis and 212 patients previously treated with first-line agents for the Ipi analysis. For the Vem cohort, a total of 49 patients were considered trial-eligible, of whom 36 (73%) received treatment. For the Ipi cohort, there were 119 trial-eligible cases of whom 43 (36%) received therapy. Factors other than eligibility criteria most frequently associated with non-treatment in these cohorts included concerns regarding treatment harm and patient preferences. In multivariable analysis, overall survival was improved in Vem cohort patients considered trial-eligible and treated compared to those who were ineligible. Within the Ipi cohort, survival was improved in trial-eligible patients regardless of whether they received Ipi compared to ineligible patients. Real-world uptake of new melanoma treatments was suboptimal, and non-use in trial-eligible patients was frequent. Future clinical trials that are more pragmatically designed to include participants who better reflect the real-world population may facilitate increased uptake of novel therapeutics into routine clinical practice.

Warfarin for prevention of thromboembolism in atrial fibrillation: comparison of patient characteristics and outcomes of the "Real-World" Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry to the RE-LY, ROCKET-AF, and ARISTOTLE trials.

PubMed

Hughey, Andrew B; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Besley, Dennis; Krol, Gregory D; Ahsan, Syed; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

2018-06-14

Randomized controlled trials (RCTs) examining warfarin use for stroke prevention in atrial fibrillation (AF) may not accurately reflect real-world populations. We aimed to determine the representativeness of the RCT populations to real-world patients and to describe differences in the characteristics of trial populations from trial eligible patients in a real-world setting. We hypothesized that a significant fraction of real-world patients would not qualify for the RE-LY, ROCKET-AF, and ARISTOTLE trials and that real-world patients qualifying for the studies may have more strokes and bleeding events. We compared the inclusion and exclusion criteria, patient characteristics, and clinical outcomes from RE-LY, ROCKET-AF, and ARISTOTLE against data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2 ), a regional network of six community- and academic-based anticoagulation clinics. Of the 1446 non-valvular AF patients in the MAQI 2 registry taking warfarin, approximately 40-60% would meet the selection criteria used in RE-LY (788, 54.5%), ROCKET-AF (566, 39.1%), and ARISTOTLE (866, 59.9%). The most common reasons for exclusion from one or more trial were anemia (15.1%), other concurrent medications (11.2%), and chronic kidney disease (9.4%). Trial-eligible MAQI 2 patients were older, more frequently female, with a higher rate of paroxysmal AF, and lower rates of congestive heart failure, previous stroke, and previous myocardial infarction than the trial populations. MAQI 2 patients eligible for each trial had a lower rate of stroke and similar rate of major bleeding than was observed in the trials. A sizable proportion of real-world AF patients managed in anticoagulation clinics would not have been eligible for the RE-LY, ROCKET-AF, and ARISOTLE trials. The expected stroke risk reduction and bleeding risk among real-world AF patients on warfarin may not be congruent with published clinical trial data.

ClinicalTrials.gov as a data source for semi-automated point-of-care trial eligibility screening.

PubMed

Pfiffner, Pascal B; Oh, JiWon; Miller, Timothy A; Mandl, Kenneth D

2014-01-01

Implementing semi-automated processes to efficiently match patients to clinical trials at the point of care requires both detailed patient data and authoritative information about open studies. To evaluate the utility of the ClinicalTrials.gov registry as a data source for semi-automated trial eligibility screening. Eligibility criteria and metadata for 437 trials open for recruitment in four different clinical domains were identified in ClinicalTrials.gov. Trials were evaluated for up to date recruitment status and eligibility criteria were evaluated for obstacles to automated interpretation. Finally, phone or email outreach to coordinators at a subset of the trials was made to assess the accuracy of contact details and recruitment status. 24% (104 of 437) of trials declaring on open recruitment status list a study completion date in the past, indicating out of date records. Substantial barriers to automated eligibility interpretation in free form text are present in 81% to up to 94% of all trials. We were unable to contact coordinators at 31% (45 of 146) of the trials in the subset, either by phone or by email. Only 53% (74 of 146) would confirm that they were still recruiting patients. Because ClinicalTrials.gov has entries on most US and many international trials, the registry could be repurposed as a comprehensive trial matching data source. Semi-automated point of care recruitment would be facilitated by matching the registry's eligibility criteria against clinical data from electronic health records. But the current entries fall short. Ultimately, improved techniques in natural language processing will facilitate semi-automated complex matching. As immediate next steps, we recommend augmenting ClinicalTrials.gov data entry forms to capture key eligibility criteria in a simple, structured format.

Eligibility and Predictors for Acute Revascularization Procedures in a Stroke Center.

PubMed

Vanacker, Peter; Lambrou, Dimitris; Eskandari, Ashraf; Mosimann, Pascal J; Maghraoui, Ali; Michel, Patrik

2016-07-01

Endovascular treatment (EVT) is a new standard of care for selected, large vessel occlusive strokes. We aimed to determine frequency of potentially eligible patients for intravenous thrombolysis (IVT) and EVT in comprehensive stroke centers. In addition, predictors of EVT eligibility were derived. Patients from a stroke center-based registry (2003-2014), admitted within 24 hours of last proof of usual health, were selected if they had all data to determine IVT and EVT eligibility according to American Heart Association/American Stroke Association (AHA/ASA) guidelines (class I-IIa recommendations). Moreover, less restrictive criteria adapted from randomized controlled trials and clinical practice were tested. Maximum onset-to-door time windows for IVT eligibility were 3.5 hours (allowing door-to-needle delay of ≤60 minutes) and 4.5 hours for EVT eligibility (door-to-groin delay ≤90 minutes). Demographic and clinical information were used in logistic regression analysis to derive variables associated with EVT eligibility. A total of 2704 patients with acute ischemic stroke were included, of which 26.8% were transfers. Of all patients with stroke arriving at our comprehensive stroke center, a total proportion of 12.4% patients was eligible for IVT. Frequency of EVT eligibility differed between AHA/ASA guidelines and less restrictive approach: 2.9% versus 4.9%, respectively, of all patients with acute ischemic stroke and 10.5% versus 17.7%, respectively, of all patients arriving within <6 hours. Predictors for AHA-EVT eligibility were younger, shorter onset-to-admission delays, higher National Institutes of Health Stroke Scale (NIHSS), decreased vigilance, hemineglect, absent cerebellar signs, atrial fibrillation, smoking, and decreasing glucose levels (area under the curve=0.86). Of patients arriving within 6 hours at a comprehensive stroke center, 10.5% are EVT eligible according to AHA/ASA criteria, 17.7% according to criteria resembling randomized controlled trials, and twice as many patients are IVT eligible (36.2%). © 2016 American Heart Association, Inc.

Diarrhea and dengue control in rural primary schools in Colombia: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Diarrheal diseases and dengue fever are major global health problems. Where provision of clean water is inadequate, water storage is crucial. Fecal contamination of stored water is a common source of diarrheal illness, but stored water also provides breeding sites for dengue vector mosquitoes. Poor household water management and sanitation are therefore potential determinants of both diseases. Little is known of the role of stored water for the combined risk of diarrhea and dengue, yet a joint role would be important for developing integrated control and management efforts. Even less is known of the effect of integrating control of these diseases in school settings. The objective of this trial was to investigate whether interventions against diarrhea and dengue will significantly reduce diarrheal disease and dengue entomological risk factors in rural primary schools. Methods/design This is a 2×2 factorial cluster randomized controlled trial. Eligible schools were rural primary schools in La Mesa and Anapoima municipalities, Cundinamarca, Colombia. Eligible pupils were school children in grades 0 to 5. Schools were randomized to one of four study arms: diarrhea interventions (DIA); dengue interventions (DEN); combined diarrhea and dengue interventions (DIADEN); and control (C). Schools were allocated publicly in each municipality (strata) at the start of the trial, obviating the need for allocation concealment. The primary outcome for diarrhea is incidence rate of diarrhea in school children and for dengue it is density of adult female Aedes aegypti per school. Approximately 800 pupils from 34 schools were enrolled in the trial with eight schools in the DIA arm, nine in the DEN, eight in the DIADEN, and nine in the control arms. The trial status as of June 2012 was: completed baseline data collections; enrollment, randomization, and allocation of schools. The trial was funded by the Research Council of Norway and the Lazos de Calandaima Foundation. Discussion This is the first trial investigating the effect of a set of integrated interventions to control both dengue and diarrhea. This is also the first trial to study the combination of diarrhea-dengue disease control in school settings. Trial registration Current Controlled Trials ISRCTN40195031 PMID:23034084

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.

OWL model of clinical trial eligibility criteria compatible with partially-known information

PubMed Central

2013-01-01

Background Clinical trials are important for patients, for researchers and for companies. One of the major bottlenecks is patient recruitment. This task requires the matching of a large volume of information about the patient with numerous eligibility criteria, in a logically-complex combination. Moreover, some of the patient’s information necessary to determine the status of the eligibility criteria may not be available at the time of pre-screening. Results We showed that the classic approach based on negation as failure over-estimates rejection when confronted with partially-known information about the eligibility criteria because it ignores the distinction between a trial for which patient eligibility should be rejected and trials for which patient eligibility cannot be asserted. We have also shown that 58.64% of the values were unknown in the 286 prostate cancer cases examined during the weekly urology multidisciplinary meetings at Rennes’ university hospital between October 2008 and March 2009. We propose an OWL design pattern for modeling eligibility criteria based on the open world assumption to address the missing information problem. We validate our model on a fictitious clinical trial and evaluate it on two real clinical trials. Our approach successfully distinguished clinical trials for which the patient is eligible, clinical trials for which we know that the patient is not eligible and clinical trials for which the patient may be eligible provided that further pieces of information (which we can identify) can be obtained. Conclusions OWL-based reasoning based on the open world assumption provides an adequate framework for distinguishing those patients who can confidently be rejected from those whose status cannot be determined. The expected benefits are a reduction of the workload of the physicians and a higher efficiency by allowing them to focus on the patients whose eligibility actually require expertise. PMID:24034867

eTACTS: a method for dynamically filtering clinical trial search results.

PubMed

Miotto, Riccardo; Jiang, Silis; Weng, Chunhua

2013-12-01

Information overload is a significant problem facing online clinical trial searchers. We present eTACTS, a novel interactive retrieval framework using common eligibility tags to dynamically filter clinical trial search results. eTACTS mines frequent eligibility tags from free-text clinical trial eligibility criteria and uses these tags for trial indexing. After an initial search, eTACTS presents to the user a tag cloud representing the current results. When the user selects a tag, eTACTS retains only those trials containing that tag in their eligibility criteria and generates a new cloud based on tag frequency and co-occurrences in the remaining trials. The user can then select a new tag or unselect a previous tag. The process iterates until a manageable number of trials is returned. We evaluated eTACTS in terms of filtering efficiency, diversity of the search results, and user eligibility to the filtered trials using both qualitative and quantitative methods. eTACTS (1) rapidly reduced search results from over a thousand trials to ten; (2) highlighted trials that are generally not top-ranked by conventional search engines; and (3) retrieved a greater number of suitable trials than existing search engines. eTACTS enables intuitive clinical trial searches by indexing eligibility criteria with effective tags. User evaluation was limited to one case study and a small group of evaluators due to the long duration of the experiment. Although a larger-scale evaluation could be conducted, this feasibility study demonstrated significant advantages of eTACTS over existing clinical trial search engines. A dynamic eligibility tag cloud can potentially enhance state-of-the-art clinical trial search engines by allowing intuitive and efficient filtering of the search result space. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

eTACTS: A Method for Dynamically Filtering Clinical Trial Search Results

PubMed Central

Miotto, Riccardo; Jiang, Silis; Weng, Chunhua

2013-01-01

Objective Information overload is a significant problem facing online clinical trial searchers. We present eTACTS, a novel interactive retrieval framework using common eligibility tags to dynamically filter clinical trial search results. Materials and Methods eTACTS mines frequent eligibility tags from free-text clinical trial eligibility criteria and uses these tags for trial indexing. After an initial search, eTACTS presents to the user a tag cloud representing the current results. When the user selects a tag, eTACTS retains only those trials containing that tag in their eligibility criteria and generates a new cloud based on tag frequency and co-occurrences in the remaining trials. The user can then select a new tag or unselect a previous tag. The process iterates until a manageable number of trials is returned. We evaluated eTACTS in terms of filtering efficiency, diversity of the search results, and user eligibility to the filtered trials using both qualitative and quantitative methods. Results eTACTS (1) rapidly reduced search results from over a thousand trials to ten; (2) highlighted trials that are generally not top-ranked by conventional search engines; and (3) retrieved a greater number of suitable trials than existing search engines. Discussion eTACTS enables intuitive clinical trial searches by indexing eligibility criteria with effective tags. User evaluation was limited to one case study and a small group of evaluators due to the long duration of the experiment. Although a larger-scale evaluation could be conducted, this feasibility study demonstrated significant advantages of eTACTS over existing clinical trial search engines. Conclusion A dynamic eligibility tag cloud can potentially enhance state-of-the-art clinical trial search engines by allowing intuitive and efficient filtering of the search result space. PMID:23916863

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.

A prospective analysis of the influence of older age on physician and patient decision-making when considering enrollment in breast cancer clinical trials (SWOG S0316).

PubMed

Javid, Sara H; Unger, Joseph M; Gralow, Julie R; Moinpour, Carol M; Wozniak, Antoinette J; Goodwin, J Wendall; Lara, Primo N; Williams, Pamela A; Hutchins, Laura F; Gotay, Carolyn C; Albain, Kathy S

2012-01-01

Patients older than 65 years are underrepresented in clinical trials. We conducted a prospective study (SWOG S0316) to determine physician- and patient-perceived barriers to breast cancer clinical trial enrollment for older patients. Eight geographically diverse SWOG institutions participated. The study assessed patients' and physicians' decisions to enroll in or decline clinical treatment trials, including demographics, trial availability, and eligibility. Patient and physician questionnaires elicited concerns related to treatment, medical status, age, family, and financial or transportation concerns. A total of 1,079 patients were registered and eligible and 909 (84%) returned for follow-up. The major reason for nonaccrual was either trial unavailability or ineligibility (60%). Older patients were less likely to be eligible for trials (65% for age ≥65 years vs. 78% for age <65 years). If eligible, trial participation rates did not differ significantly by age (34% for age ≥65 years vs. 40% for age <65 years). Patients ≥65 years more often were concerned about side effects, had friends opposed to participation, or believed that participation would not benefit other generations. When trials were available and patients were eligible, physicians discussed trial participation with 76% of patients <65 years versus 58% of patients ≥65 years of age. For patients ≥65 years, 11% of physicians indicated age as a reason they did not enroll a patient in a clinical trial. Trial unavailability or patient ineligibility were the major reasons for lack of enrollment in breast cancer clinical trials for patients of all ages in this prospective study. Older patients were less likely to be eligible for trials, but if eligible they participated at similar rates to younger patients.

Experience Corps: a dual trial to promote the health of older adults and children's academic success.

PubMed

Fried, Linda P; Carlson, Michelle C; McGill, Sylvia; Seeman, Teresa; Xue, Qian-Li; Frick, Kevin; Tan, Erwin; Tanner, Elizabeth K; Barron, Jeremy; Frangakis, Constantine; Piferi, Rachel; Martinez, Iveris; Gruenewald, Tara; Martin, Barbara K; Berry-Vaughn, Laprisha; Stewart, John; Dickersin, Kay; Willging, Paul R; Rebok, George W

2013-09-01

As the population ages, older adults are seeking meaningful, and impactful, post-retirement roles. As a society, improving the health of people throughout longer lives is a major public health goal. This paper presents the design and rationale for an effectiveness trial of Experience Corps™, an intervention created to address both these needs. This trial evaluates (1) whether senior volunteer roles within Experience Corps™ beneficially impact children's academic achievement and classroom behavior in public elementary schools and (2) impact on the health of volunteers. Dual evaluations of (1) an intention-to-treat trial randomizing eligible adults 60 and older to volunteer service in Experience Corps™, or to a control arm of usual volunteering opportunities, and (2) a comparison of eligible public elementary schools receiving Experience Corps™ to matched, eligible control schools in a 1:1 control:intervention school ratio. For older adults, the primary outcome is decreased disability in mobility and Instrumental Activities of Daily Living (IADL). Secondary outcomes are decreased frailty, falls, and memory loss; slowed loss of strength, balance, walking speed, cortical plasticity, and executive function; objective performance of IADLs; and increased social and psychological engagement. For children, primary outcomes are improved reading achievement and classroom behavior in Kindergarten through the 3rd grade; secondary outcomes are improvements in school climate, teacher morale and retention, and teacher perceptions of older adults. This trial incorporates principles and practices of community-based participatory research and evaluates the dual benefit of a single intervention, versus usual opportunities, for two generations: older adults and children. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Evaluating the Impact of a School-Based Helmet Promotion Program on Eligible Adolescent Drivers: Different Audiences, Different Needs?

ERIC Educational Resources Information Center

Germeni, Evi; Lionis, Christos; Kalampoki, Vassiliki; Davou, Bettina; Belechri, Maria; Petridou, Eleni

2010-01-01

The school environment has been often identified as a prosperous venue for public health improvement. This study is a cluster randomized controlled trial evaluating the impact of a school-based helmet promotion program on knowledge, attitudes and practices of eligible adolescent drivers. Four public, four private and four vocational high schools…

Reflecting on the methodological challenges of recruiting to a United Kingdom-wide, multi-centre, randomised controlled trial in gynaecology outpatient settings

PubMed Central

2013-01-01

Background Successful recruitment of participants to any trial is central to its success. Trial results are routinely published, and recruitment is often cited to be slower and more difficult than anticipated. This article reflects on the methodological challenges of recruiting women with prolapse attending United Kingdom (UK) gynaecology outpatient clinics to a multi-centre randomised controlled trial (RCT) of physiotherapy, and the systems put in place in an attempt to address them. Methods Gynaecology outpatients with symptomatic prolapse were to be recruited over a 16-month period from 14 UK hospitals and one New Zealand hospital. Eligible women were informed about the trial by their gynaecologist and informed consent was obtained by the central trial office. Recruitment difficulties were encountered early on, and a number of strategies were employed to try to improve recruitment. Results Some strategies were more successful than others and they differed in the resources required. Actions that facilitated recruitment included increasing recruiting centres to 23 UK and two international hospitals, good centre support, using processes embedded in clinical practice, and good communication between the trial office, collaborators and participants. Collaborator incentives, whereby staff involved received the benefit immediately, were more successful than a nominal monetary payment per woman randomised. Barriers to recruitment included fewer eligible women than anticipated, patient’s preference to receive active treatment rather than allocation to the control group, lack of support staff and high staff turnover. Geographical variations in Primary Care Trust Research Management and Governance approval systems and general practitioner (GP) referral procedures also impacted negatively on recruitment. Conclusions Our article reflects on the methodological challenges of recruiting to a multi-centre RCT in a UK gynaecology setting. Effective interventions included increasing the number of recruiting centres and providing collaborator incentives. Barriers to recruitment included fewer eligible women than anticipated, patient’s preference to be allocated to the treatment group, lack of support staff, and variations in approval systems and GP referral procedures. To improve the evidence base on clinical trial recruitment, trialists need to publish their experiences and lessons learned. Future RCTs should evaluate, where possible, the effect of strategies designed to improve recruitment and retention. Trial registration Current Controlled Trials ISRCTN35911035 PMID:24228935

Diarrhea and dengue control in rural primary schools in Colombia: study protocol for a randomized controlled trial.

PubMed

Overgaard, Hans J; Alexander, Neal; Mátiz, Maria Ines; Jaramillo, Juan Felipe; Olano, Victor Alberto; Vargas, Sandra; Sarmiento, Diana; Lenhart, Audrey; Seidu, Razak; Stenström, Thor Axel

2012-10-03

Diarrheal diseases and dengue fever are major global health problems. Where provision of clean water is inadequate, water storage is crucial. Fecal contamination of stored water is a common source of diarrheal illness, but stored water also provides breeding sites for dengue vector mosquitoes. Poor household water management and sanitation are therefore potential determinants of both diseases. Little is known of the role of stored water for the combined risk of diarrhea and dengue, yet a joint role would be important for developing integrated control and management efforts. Even less is known of the effect of integrating control of these diseases in school settings. The objective of this trial was to investigate whether interventions against diarrhea and dengue will significantly reduce diarrheal disease and dengue entomological risk factors in rural primary schools. This is a 2×2 factorial cluster randomized controlled trial. Eligible schools were rural primary schools in La Mesa and Anapoima municipalities, Cundinamarca, Colombia. Eligible pupils were school children in grades 0 to 5. Schools were randomized to one of four study arms: diarrhea interventions (DIA); dengue interventions (DEN); combined diarrhea and dengue interventions (DIADEN); and control (C). Schools were allocated publicly in each municipality (strata) at the start of the trial, obviating the need for allocation concealment. The primary outcome for diarrhea is incidence rate of diarrhea in school children and for dengue it is density of adult female Aedes aegypti per school. Approximately 800 pupils from 34 schools were enrolled in the trial with eight schools in the DIA arm, nine in the DEN, eight in the DIADEN, and nine in the control arms. The trial status as of June 2012 was: completed baseline data collections; enrollment, randomization, and allocation of schools. The trial was funded by the Research Council of Norway and the Lazos de Calandaima Foundation. This is the first trial investigating the effect of a set of integrated interventions to control both dengue and diarrhea. This is also the first trial to study the combination of diarrhea-dengue disease control in school settings. Current Controlled Trials ISRCTN40195031.

Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial.

PubMed

Corbacioglu, Selim; Cesaro, Simone; Faraci, Maura; Valteau-Couanet, Dominique; Gruhn, Bernd; Rovelli, Attilio; Boelens, Jaap J; Hewitt, Annette; Schrum, Johanna; Schulz, Ansgar S; Müller, Ingo; Stein, Jerry; Wynn, Robert; Greil, Johann; Sykora, Karl-Walter; Matthes-Martin, Susanne; Führer, Monika; O'Meara, Anne; Toporski, Jacek; Sedlacek, Petr; Schlegel, Paul G; Ehlert, Karoline; Fasth, Anders; Winiarski, Jacek; Arvidson, Johan; Mauz-Körholz, Christine; Ozsahin, Hulya; Schrauder, Andre; Bader, Peter; Massaro, Joseph; D'Agostino, Ralph; Hoyle, Margaret; Iacobelli, Massimo; Debatin, Klaus-Michael; Peters, Christina; Dini, Giorgio

2012-04-07

Hepatic veno-occlusive disease is a leading cause of morbidity and mortality after haemopoietic stem-cell transplantation (HSCT). We aimed to assess whether defibrotide can reduce the incidence of veno-occlusive disease in this setting. In our phase 3 open-label, randomised controlled trial, we enrolled patients at 28 European university hospitals or academic medical centres. Eligible patients were younger than 18 years, had undergone myeloablative conditioning before allogeneic or autologous HSCT, and had one or more risk factor for veno-occlusive disease based on modified Seattle criteria. We centrally assigned eligible participants on the basis of a computer-generated randomisation sequence (1:1), stratified by centre and presence of osteopetrosis, to receive intravenous defibrotide prophylaxis (treatment group) or not (control group). The primary endpoint was incidence of veno-occlusive disease by 30 days after HSCT, adjudicated by a masked, independent review committee, in eligible patients who consented to randomisation (intention-to-treat population), and was assessed with a competing risk approach. Patients in either group who developed veno-occlusive disease received defibrotide for treatment. We assessed adverse events to 180 days after HSCT in all patients who received allocated prophylaxis. This trial is registered with ClinicalTrials.gov, number NCT00272948. Between Jan 25, 2006, and Jan 29, 2009, we enrolled 356 eligible patients to the intention-to-treat population. 22 (12%) of 180 patients randomly allocated to the defibrotide group had veno-occlusive disease by 30 days after HSCT compared with 35 (20%) of 176 controls (risk difference -7·7%, 95% CI -15·3 to -0·1; Z test for competing risk analysis p=0·0488; log-rank test p=0·0507). 154 (87%) of 177 patients in the defibrotide group had adverse events by day 180 compared with 155 (88%) of 176 controls. Defibrotide prophylaxis seems to reduce incidence of veno-occlusive disease and is well tolerated. Thus, such prophylaxis could present a useful clinical option for this serious complication of HSCT. Gentium SpA, European Group for Blood and Marrow Transplantation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Automated matching software for clinical trials eligibility: measuring efficiency and flexibility.

PubMed

Penberthy, Lynne; Brown, Richard; Puma, Federico; Dahman, Bassam

2010-05-01

Clinical trials (CT) serve as the media that translates clinical research into standards of care. Low or slow recruitment leads to delays in delivery of new therapies to the public. Determination of eligibility in all patients is one of the most important factors to assure unbiased results from the clinical trials process and represents the first step in addressing the issue of under representation and equal access to clinical trials. This is a pilot project evaluating the efficiency, flexibility, and generalizibility of an automated clinical trials eligibility screening tool across 5 different clinical trials and clinical trial scenarios. There was a substantial total savings during the study period in research staff time spent in evaluating patients for eligibility ranging from 165h to 1329h. There was a marked enhancement in efficiency with the automated system for all but one study in the pilot. The ratio of mean staff time required per eligible patient identified ranged from 0.8 to 19.4 for the manual versus the automated process. The results of this study demonstrate that automation offers an opportunity to reduce the burden of the manual processes required for CT eligibility screening and to assure that all patients have an opportunity to be evaluated for participation in clinical trials as appropriate. The automated process greatly reduces the time spent on eligibility screening compared with the traditional manual process by effectively transferring the load of the eligibility assessment process to the computer. Copyright (c) 2010 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.

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

PubMed

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

2014-08-28

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

Case-based reasoning using electronic health records efficiently identifies eligible patients for clinical trials

PubMed Central

Miotto, Riccardo

2015-01-01

Objective To develop a cost-effective, case-based reasoning framework for clinical research eligibility screening by only reusing the electronic health records (EHRs) of minimal enrolled participants to represent the target patient for each trial under consideration. Materials and Methods The EHR data—specifically diagnosis, medications, laboratory results, and clinical notes—of known clinical trial participants were aggregated to profile the “target patient” for a trial, which was used to discover new eligible patients for that trial. The EHR data of unseen patients were matched to this “target patient” to determine their relevance to the trial; the higher the relevance, the more likely the patient was eligible. Relevance scores were a weighted linear combination of cosine similarities computed over individual EHR data types. For evaluation, we identified 262 participants of 13 diversified clinical trials conducted at Columbia University as our gold standard. We ran a 2-fold cross validation with half of the participants used for training and the other half used for testing along with other 30 000 patients selected at random from our clinical database. We performed binary classification and ranking experiments. Results The overall area under the ROC curve for classification was 0.95, enabling the highlight of eligible patients with good precision. Ranking showed satisfactory results especially at the top of the recommended list, with each trial having at least one eligible patient in the top five positions. Conclusions This relevance-based method can potentially be used to identify eligible patients for clinical trials by processing patient EHR data alone without parsing free-text eligibility criteria, and shows promise of efficient “case-based reasoning” modeled only on minimal trial participants. PMID:25769682

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.

A pilot randomised controlled trial of negative pressure wound therapy to treat grade III/IV pressure ulcers [ISRCTN69032034

PubMed Central

2012-01-01

Background Negative pressure wound therapy (NPWT) is widely promoted as a treatment for full thickness wounds; however, there is a lack of high-quality research evidence regarding its clinical and cost effectiveness. A trial of NPWT for the treatment of grade III/IV pressure ulcers would be worthwhile but premature without assessing whether such a trial is feasible. The aim of this pilot randomised controlled trial was to assess the feasibility of conducting a future full trial of NPWT for the treatment of grade III and IV pressure ulcers and to pilot all aspects of the trial. Methods This was a two-centre (acute and community), pilot randomised controlled trial. Eligible participants were randomised to receive either NPWT or standard care (SC) (spun hydrocolloid, alginate or foam dressings). Outcome measures were time to healing of the reference pressure ulcer, recruitment rates, frequency of treatment visits, resources used and duration of follow-up. Results Three hundred and twelve patients were screened for eligibility into this trial over a 12-month recruitment period and 12/312 participants (3.8%) were randomised: 6 to NPWT and 6 to SC. Only one reference pressure ulcer healed (NPWT group) during follow-up (time to healing 79 days). The mean number of treatment visits per week was 3.1 (NPWT) and 5.7 (SC); 6/6 NPWT and 1/6 SC participants withdrew from their allocated trial treatment. The mean duration of follow-up was 3.8 (NPWT) and 5.0 (SC) months. Conclusions This pilot trial yielded vital information for the planning of a future full study including projected recruitment rate, required duration of follow-up and extent of research nurse support required. Data were also used to inform the cost-effectiveness and value of information analyses, which were conducted alongside the pilot trial. Trial registration Current Controlled Trials ISRCTN69032034. PMID:22839453

Reflecting on the methodological challenges of recruiting to a United Kingdom-wide, multi-centre, randomised controlled trial in gynaecology outpatient settings.

PubMed

Dickson, Sylvia; Logan, Janet; Hagen, Suzanne; Stark, Diane; Glazener, Cathryn; McDonald, Alison M; McPherson, Gladys

2013-11-15

Successful recruitment of participants to any trial is central to its success. Trial results are routinely published, and recruitment is often cited to be slower and more difficult than anticipated. This article reflects on the methodological challenges of recruiting women with prolapse attending United Kingdom (UK) gynaecology outpatient clinics to a multi-centre randomised controlled trial (RCT) of physiotherapy, and the systems put in place in an attempt to address them. Gynaecology outpatients with symptomatic prolapse were to be recruited over a 16-month period from 14 UK hospitals and one New Zealand hospital. Eligible women were informed about the trial by their gynaecologist and informed consent was obtained by the central trial office. Recruitment difficulties were encountered early on, and a number of strategies were employed to try to improve recruitment. Some strategies were more successful than others and they differed in the resources required. Actions that facilitated recruitment included increasing recruiting centres to 23 UK and two international hospitals, good centre support, using processes embedded in clinical practice, and good communication between the trial office, collaborators and participants. Collaborator incentives, whereby staff involved received the benefit immediately, were more successful than a nominal monetary payment per woman randomised. Barriers to recruitment included fewer eligible women than anticipated, patient's preference to receive active treatment rather than allocation to the control group, lack of support staff and high staff turnover. Geographical variations in Primary Care Trust Research Management and Governance approval systems and general practitioner (GP) referral procedures also impacted negatively on recruitment. Our article reflects on the methodological challenges of recruiting to a multi-centre RCT in a UK gynaecology setting. Effective interventions included increasing the number of recruiting centres and providing collaborator incentives. Barriers to recruitment included fewer eligible women than anticipated, patient's preference to be allocated to the treatment group, lack of support staff, and variations in approval systems and GP referral procedures. To improve the evidence base on clinical trial recruitment, trialists need to publish their experiences and lessons learned. Future RCTs should evaluate, where possible, the effect of strategies designed to improve recruitment and retention. Current Controlled Trials ISRCTN35911035.

Hyperbaric oxygen therapy for Bell's palsy.

PubMed

Holland, N Julian; Bernstein, Jonathan M; Hamilton, John W

2012-02-15

Bell's palsy is an idiopathic, acute unilateral facial weakness that evolves rapidly and is maximal within two days. Moderate ear discomfort, sensitivity to sound and reduced tearing may occur. To assess the effects of hyperbaric oxygen therapy on recovery of facial function in adults with moderate to severe Bell's palsy. We searched the Cochrane Neuromuscular Disease Group Specialized Register (January 2012), CENTRAL (2011, Issue 4), MEDLINE (January 1966 to January 2012), EMBASE (January 1980 to January 2012), CINAHL (1937 to January 2012), AMED (1985 to January 2012), LILACS (January 1982 to January 2012). In addition we made a systematic search for relevant controlled trials in specific hyperbaric literature sources. Randomised controlled trials or quasi-randomised controlled trials of adults (over 16 years of age) undergoing hyperbaric oxygen therapy for moderate to severe Bell's palsy. We considered studies to be of sufficient quality for inclusion in the review only if there was blinding in the assessment of the facial palsy grade. We planned to include studies of HBOT used as adjuvant therapy, or in addition to routine medical therapy (including corticosteroids or antivirals, or both). Both treatment and control groups were to receive the same baseline therapy. HBOT had to be delivered at concentrations greater than or equal to 1.2 ATA in a hyperbaric oxygen chamber as a series of dives of 30 to 120 minutes. Two reviewers independently assessed eligibility and study quality and extracted data. We contacted study authors for additional information. Our searches found no randomised controlled trials or quasi-randomised controlled trials that met the eligibility criteria for this review.There is very low quality evidence from one randomised trial involving 79 participants with acute Bell's palsy, but this study was excluded as the outcome assessor was not blinded to treatment allocation and thus did not meet pre-defined eligibility criteria. The trial compared 42 people who received hyperbaric oxygen therapy (2.8 atmospheres for 60 minutes twice daily, five days per week until the facial palsy resolved; maximum 30 'dives') and placebo tablets with 37 people who received placebo hyperbaric oxygen therapy (achieving only a normal partial pressure of oxygen) and prednisone (40 mg twice daily, reducing over eight days). Facial function recovered in more participants treated with hyperbaric oxygen therapy than with prednisone (hyperbaric oxygen therapy, 40/42 (95%); prednisone, 28/37 (76%); risk ratio 1.26, 95% CI 1.04 to 1.53). There were no reported major complications and all participants completed the trial. Very low quality evidence from one trial suggests that hyperbaric oxygen therapy may be an effective treatment for moderate to severe Bell's palsy, but this study was excluded as the outcome assessor was not blinded to treatment allocation. Further randomised controlled trials are needed.

Non-entry of eligible patients into the Australasian Laparoscopic Colon Cancer Study.

PubMed

Abraham, Ned S; Hewett, Peter; Young, Jane M; Solomon, Michael J

2006-09-01

There is currently a need to assess the reasons for non-entry of eligible patients into surgical randomized controlled trials to determine measures to improve the low recruitment rates in such trials. Reasons for non-entry of all eligible patients not recruited into the Australasian Laparoscopic Colon Cancer Study were prospectively recorded using a survey completed by the participating surgeons for a period of 6 months. In the 6-month period of the study, 51 (45%) out of 113 eligible patients examined by the 18 actively participating surgeons were recruited into the trial. Eighty-nine reasons were recorded for the non-entry of the 62 eligible patients. The most commonly recorded reason was preference for one form of surgery (42%) or the surgeon (31%) by the patient (45 patients (73%) in total). This was followed by lack of time (10 patients (16%)), hospital accreditation (7 patients (11%)) or staffing/equipment (6 patients (10%)). Concern about the doctor-patient relationship or causing the patient anxiety was recorded for three (5%) and two (3%) patients, respectively. Recruitment was positively associated with the availability of a data manager (chi2 = 19.91; P < 0.001, odds ratio (95% confidence interval) = 9.50 (3.53-25.53)) and negatively associated with an increased caseload (more than five eligible patients seen by the surgeon in the study period) (continuity adjusted chi2 = 16.052; P < 0.001, odds ratio (95% confidence interval) = 0.11(0.04-0.30)). Having a preference for one form of surgery by the patient or the surgeon was the most common reason for non-entry of eligible patients in the Australasian Laparoscopic Colon Cancer Study. Concern about the doctor-patient relationship played a minimal role in determining the outcome of recruitment. Patient and surgeon preferences, caseload and the distribution of supportive staff such as data managers according to patient population density should be considered in the planning of future trials.

Effect of characteristics of women on attendance in blind and non-blind randomised trials: analysis of recruitment data from the EPHT Trial.

PubMed

Veerus, Piret; Fischer, Krista; Hemminki, Elina; Hovi, Sirpa-Liisa; Hakama, Matti

2016-10-18

To analyse the effect of women's characteristics on their willingness to join a blind or a non-blind subtrial or to be excluded by physicians. Primary prevention trial of postmenopausal hormone therapy (HT). A 2×2, randomised design with a non-blind HT arm or control arm and a blind HT arm or placebo arm. 3 clinical centres in Estonia. Interest in joining the trial was asked in a questionnaire together with demographic and health status data. Interested and eligible women were invited to a health examination that also informed whether they belonged to a blind or to a non-blind subtrial; the arm was not revealed. Trial physicians made further exclusions when checking the women's eligibility. Thereafter, informed consent was asked as detailed in the flow chart. Comparisons were made between non-blind and blind subtrials. Analyses were carried out for each of the background variables. The proportion of willingness, eligibility and attendance. Women randomised to the non-blind subtrial were more willing to join (relative risk (RR) 1.17) and more likely to be found eligible by physicians (RR 1.10) than women in the blind subtrial, resulting in larger attendance (RR 1.29). Women with higher education were differentially more willing to join the non-blind trial (RR 1.29) than those with basic education (RR 1.08); the differential willingness of never-smokers (RR 1.20) was larger than that of current smokers (RR 1.07). The differential exclusion by physicians by education and smoking were small. Some subjective symptoms (eg, diarrhoea/constipation, stomach pain) had reverse differential effects on attendance in the non-blind subtrial in comparison to the blind subtrial. Menopausal symptoms did not affect the differential interest, eligibility or attendance. Blinding in RCT reduces attendance, due to decisions of the women and the trial physicians. Differential attendance by blinding may affect the generalisability of the results from trials. ISRCTN35338757. 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/.

Control group design, contamination and drop-out in exercise oncology trials: a systematic review.

PubMed

Steins Bisschop, Charlotte N; Courneya, Kerry S; Velthuis, Miranda J; Monninkhof, Evelyn M; Jones, Lee W; Friedenreich, Christine; van der Wall, Elsken; Peeters, Petra H M; May, Anne M

2015-01-01

Important considerations for exercise trials in cancer patients are contamination and differential drop-out among the control group members that might jeopardize the internal validity. This systematic review provides an overview of different control groups design characteristics of exercise-oncology trials and explores the association with contamination and drop-out rates. Randomized controlled exercise-oncology trials from two Cochrane reviews were included. Additionally, a computer-aided search using Medline (Pubmed), Embase and CINAHL was conducted after completion date of the Cochrane reviews. Eligible studies were classified according to three control group design characteristics: the exercise instruction given to controls before start of the study (exercise allowed or not); and the intervention the control group was offered during (any (e.g., education sessions or telephone contacts) or none) or after (any (e.g., cross-over or exercise instruction) or none) the intervention period. Contamination (yes or no) and excess drop-out rates (i.e., drop-out rate of the control group minus the drop-out rate exercise group) were described according to the three design characteristics of the control group and according to the combinations of these three characteristics; so we additionally made subgroups based on combinations of type and timing of instructions received. 40 exercise-oncology trials were included based on pre-specified eligibility criteria. The lowest contamination (7.1% of studies) and low drop-out rates (excess drop-out rate -4.7±9.2) were found in control groups offered an intervention after the intervention period. When control groups were offered an intervention both during and after the intervention period, contamination (0%) and excess drop-out rates (-10.0±12.8%) were even lower. Control groups receiving an intervention during and after the study intervention period have lower contamination and drop-out rates. The present findings can be considered when designing future exercise-oncology trials.

Periodontal treatment during pregnancy and birth outcomes: a meta-analysis of randomised trials.

PubMed

George, Ajesh; Shamim, Simin; Johnson, Maree; Ajwani, Shilpi; Bhole, Sameer; Blinkhorn, Anthony; Ellis, Sharon; Andrews, Karen

2011-06-01

The objective of this review was to conduct a meta-analysis of all up-to-date randomised control trials to determine whether periodontal treatment during pregnancy has the potential of reducing preterm birth and low birth weight incidence. Bibliographic databases MEDLINE (1966-present), EMBASE (1980-present), CINAHL (1982-present) and the Cochrane library up to and including 2010 Issue 10 were searched. The reference list of included studies and reviews were also searched for additional literature. Eligible studies were, published and ongoing randomised control trials that compared pregnancy outcomes for pregnant women who received periodontal treatment during the prenatal period. Two of the investigators independently assessed the studies and then extracted and summarised data from eligible trials. Extracted data were entered into Review Manager software and analysed. A total of 5645 pregnant women participated in the 10 eligible trials. Meta-analysis found that periodontal treatment significantly lowered preterm birth (odd ratio 0.65; 95% confidence interval, 0.45-0.93; P = 0.02) and low birth weight (odd ratio 0.53; 95% confidence interval, 0.31-0.92; P = 0.02) rates while no significant difference was found for spontaneous abortion/stillbirth (odd ratio 0.71; 95% confidence interval, 0.43-1.16; P = 0.17). Moderate heterogeneity was observed among the studies for preterm birth and low birth weight. Subgroup analysis showed significant effect of periodontal treatment in pregnant women with low rate of previous preterm birth/low birth weight (odd ratio 0.35; 95% confidence interval, 017-0.70; P = 0.003) and less severe periodontal disease (odd ratio 0.49; confidence interval, 028-0.87; P = 0.01) as defined by probing depth. The cumulative evidence suggests that periodontal treatment during pregnancy may reduce preterm birth and low birth weight incidence. However, these findings need to be further validated through larger more targeted randomised control trials. © 2011 The Authors. International Journal of Evidence-Based Healthcare © 2011 The Joanna Briggs Institute.

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.

Does conflict control occur without awareness? Evidence from an ERP study.

PubMed

Wang, Baoxi; Xiang, Ling; Li, Juan

2013-01-15

The relationship between conflict control and awareness has attracted extensive interest. Although researchers have investigated the relationship between response conflict and awareness, it still remains unclear whether stimulus conflict can occur outside of awareness. In addition, previous studies on the role of awareness in conflict control have ignored the fact that conflict control includes both conflict detection and resolution. A modified version of the flanker task was used to manipulate stimulus and response conflicts under both masked and unmasked conditions. The masked condition elicited a sequence of distinct event-related potential components that were also observed in the unmasked condition. N2 amplitudes presented the following pattern: incongruent-eligible>incongruent-ineligible>congruent, they did not show any difference under the masked and unmasked conditions, suggesting that detection of stimulus-related conflict revealed by the comparison between incongruent-ineligible and congruent trials, and response-related conflict revealed by the comparison between incongruent-eligible and incongruent-ineligible trials can occur in the absence of awareness, and unconscious conflict detection might involve the same neural network employed for conscious conflict detection. Late positive component (LPC) amplitudes also presented as incongruent-eligible>incongruent-ineligible>congruent at CPz and Pz, irrespective of conscious awareness. However, LPC amplitudes under the masked condition were markedly reduced compared to unmasked trials. These LPC findings suggest that stimulus- and response-related conflict resolution can occur in the absence of awareness; furthermore, unconscious conflict resolution might involve a weaker cognitive control network compared to conscious conflict resolution. These findings have important implications for the theories concerning the relationship between cognitive control and awareness. Copyright © 2012 Elsevier B.V. All rights reserved.

Central coordination as an alternative for local coordination in a multicenter randomized controlled trial: the FAITH trial experience.

PubMed

Zielinski, Stephanie M; Viveiros, Helena; Heetveld, Martin J; Swiontkowski, Marc F; Bhandari, Mohit; Patka, Peter; Van Lieshout, Esther M M

2012-01-08

Surgeons in the Netherlands, Canada and the US participate in the FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures). Dutch sites are managed and visited by a financed central trial coordinator, whereas most Canadian and US sites have local study coordinators and receive per patient payment. This study was aimed to assess how these different trial management strategies affected trial performance. Details related to obtaining ethics approval, time to trial start-up, inclusion, and percentage completed follow-ups were collected for each trial site and compared. Pre-trial screening data were compared with actual inclusion rates. Median trial start-up ranged from 41 days (P25-P75 10-139) in the Netherlands to 232 days (P25-P75 98-423) in Canada (p = 0.027). The inclusion rate was highest in the Netherlands; median 1.03 patients (P25-P75 0.43-2.21) per site per month, representing 34.4% of the total eligible population. It was lowest in Canada; 0.14 inclusions (P25-P75 0.00-0.28), representing 3.9% of eligible patients (p < 0.001). The percentage completed follow-ups was 83% for Canadian and Dutch sites and 70% for US sites (p = 0.217). In this trial, a central financed trial coordinator to manage all trial related tasks in participating sites resulted in better trial progression and a similar follow-up. It is therefore a suitable alternative for appointing these tasks to local research assistants. The central coordinator approach can enable smaller regional hospitals to participate in multicenter randomized controlled trials. Circumstances such as available budget, sample size, and geographical area should however be taken into account when choosing a management strategy. ClinicalTrials.gov: NCT00761813.

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

How Have Cancer Clinical Trial Eligibility Criteria Evolved Over Time?

PubMed Central

Yaman, Anil; Chakrabarti, Shreya; Sen, Anando; Weng, Chunhua

2016-01-01

Knowledge reuse of cancer trial designs may benefit from a temporal understanding of the evolution of the target populations of cancer studies over time. Therefore, we conducted a retrospective analysis of the trends of cancer trial eligibility criteria between 1999 and 2014. The yearly distributions of eligibility concepts for chemicals and drugs, procedures, observations, and medical conditions extracted from free-text eligibility criteria of 32,000 clinical trials for 89 cancer types were analyzed. We identified the concepts that trend upwards or downwards in all or selected cancer types, and the concepts that show anomalous trends for some cancers. Later, concept trends were studied in a disease-specific manner and illustrated for breast cancer. Criteria trends observed in this study are also validated and interpreted using evidence from the existing medical literature. This study contributes a method for concept trend analysis and original knowledge of the trends in cancer clinical trial eligibility criteria. PMID:27570681

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

PubMed Central

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

2014-01-01

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

Effectiveness of off-the-shelf footwear in reducing foot pain in Australian Department of Veterans’ Affairs recipients not eligible for medical grade footwear: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Foot pain is highly prevalent in older people, and in many cases is associated with wearing inadequate footwear. In Australia, the Department of Veterans’ Affairs (DVA) covers the costs of medical grade footwear for veterans who have severe foot deformity. However, there is a high demand for footwear by veterans with foot pain who do not meet this eligibility criterion. Therefore, this article describes the design of a randomized controlled trial to evaluate the effectiveness of low cost, off-the-shelf footwear in reducing foot pain in DVA recipients who are currently not eligible for medical grade footwear. Methods One hundred and twenty DVA clients with disabling foot pain residing in Melbourne, Australia, who are not eligible for medical grade footwear will be recruited from the DVA database, and will be randomly allocated to an intervention group or a ‘usual care’ control group. The intervention group will continue to receive their usual DVA-subsidized podiatry care in addition to being provided with low-cost, supportive footwear (Dr Comfort®, Vasyli Medical, Labrador, Queensland, Australia). The control group will also continue to receive DVA-subsidized podiatry care, but will not be provided with the footwear until the completion of the study. The primary outcome measure will be pain subscale on the Foot Health Status Questionnaire (FHSQ), measured at baseline and 4, 8, 12 and 16 weeks. Secondary outcome measures measured at baseline and 16 weeks will include the function subscale of the FHSQ, the Manchester Foot Pain and Disability Index, the number of DVA podiatry treatments required during the study period, general health-related quality of life (using the Short Form 12® Version 2.0), the number of falls experienced during the follow-up period, the Timed Up and Go test, the presence of hyperkeratotic lesions (corns and calluses), the number of participants using co-interventions to relieve foot pain, and participants’ perception of overall treatment effect. Data will be analyzed using the intention-to-treat principle. Discussion This study is the first randomized controlled trial to evaluate the effectiveness of off-the-shelf footwear in reducing foot pain in DVA recipients. The intervention has been pragmatically designed to ensure that the study findings can be implemented into policy and clinical practice if found to be effective. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12612000322831 PMID:23782557

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

Local recruitment experience in a study comparing the effectiveness of a low glycaemic index diet with a low calorie healthy eating approach at achieving weight loss and reducing the risk of endometrial cancer in women with polycystic ovary syndrome (PCOS).

PubMed

Atiomo, William; Read, Anna; Golding, Mary; Silcocks, Paul; Razali, Nuguelis; Sarkar, Sabitabrata; Hardiman, Paul; Thornton, Jim

2009-09-01

Feasibility of a clinical-trial comparing a low-glycaemic diet with a low-calorie healthy eating approach at achieving weight loss and reducing the risk of endometrial cancer in women with PCOS. A pilot Randomised-Controlled-Trial using different recruitment strategies. A University Hospital in the United Kingdom. Women seen at specialist gynaecology clinics over a 12 month period in one University Hospital, and women self identified through a website and posters. Potential recruits were assessed for eligibility, gave informed consent, randomised, treated and assessed as in the definitive trial. Eligibility and recruitment rates, compliance with the allocated diet for 6 months and with clinical assessments, blood tests, pelvic ultrasound scans and endometrial biopsies. 1433 new and 2598 follow up patients were seen in 153 gynaecology clinics for over 12 months. 441 (11%) potentially eligible women were identified, 19 (0.4%) of whom met the trial entry criteria. Eleven consented to take part, of which 8 (73%) completed the study. Planned future trials on over-weight women with PCOS should be multicentre and should incorporate primary care. This data will help other researchers plan and calculate the sample size and potential recruitment rates in future clinical trials in PCOS. The results will also be useful for inclusion in future meta-analyses.

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.

A Method for Analyzing Commonalities in Clinical Trial Target Populations

PubMed Central

He, Zhe; Carini, Simona; Hao, Tianyong; Sim, Ida; Weng, Chunhua

2014-01-01

ClinicalTrials.gov presents great opportunities for analyzing commonalities in clinical trial target populations to facilitate knowledge reuse when designing eligibility criteria of future trials or to reveal potential systematic biases in selecting population subgroups for clinical research. Towards this goal, this paper presents a novel data resource for enabling such analyses. Our method includes two parts: (1) parsing and indexing eligibility criteria text; and (2) mining common eligibility features and attributes of common numeric features (e.g., A1c). We designed and built a database called “Commonalities in Target Populations of Clinical Trials” (COMPACT), which stores structured eligibility criteria and trial metadata in a readily computable format. We illustrate its use in an example analytic module called CONECT using COMPACT as the backend. Type 2 diabetes is used as an example to analyze commonalities in the target populations of 4,493 clinical trials on this disease. PMID:25954450

Management of haemothoraces in blunt thoracic trauma: study protocol for a randomised controlled trial.

PubMed

Carver, David A; Bressan, Alexsander K; Schieman, Colin; Grondin, Sean C; Kirkpatrick, Andrew W; Lall, Rohan; McBeth, Paul B; Dunham, Michael B; Ball, Chad G

2018-03-03

Haemothorax following blunt thoracic trauma is a common source of morbidity and mortality. The optimal management of moderate to large haemothoraces has yet to be defined. Observational data have suggested that expectant management may be an appropriate strategy in stable patients. This study aims to compare the outcomes of patients with haemothoraces following blunt thoracic trauma treated with either chest drainage or expectant management. This is a single-centre, dual-arm randomised controlled trial. Patients presenting with a moderate to large sized haemothorax following blunt thoracic trauma will be assessed for eligibility. Eligible patients will then undergo an informed consent process followed by randomisation to either (1) chest drainage (tube thoracostomy) or (2) expectant management. These groups will be compared for the rate of additional thoracic interventions, major thoracic complications, length of stay and mortality. This study has been approved by the institution's research ethics board and registered with ClinicalTrials.gov. All eligible participants will provide informed consent prior to randomisation. The results of this study may provide guidance in an area where there remains significant variation between clinicians. The results of this study will be published in peer-reviewed journals and presented at national and international conferences. NCT03050502. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Optimizing stroke clinical trial design: estimating the proportion of eligible patients.

PubMed

Taylor, Alexis; Castle, Amanda; Merino, José G; Hsia, Amie; Kidwell, Chelsea S; Warach, Steven

2010-10-01

Clinical trial planning and site selection require an accurate estimate of the number of eligible patients at each site. In this study, we developed a tool to calculate the proportion of patients who would meet a specific trial's age, baseline severity, and time to treatment inclusion criteria. From a sample of 1322 consecutive patients with acute ischemic cerebrovascular syndromes, we developed regression curves relating the proportion of patients within each range of the 3 variables. We used half the patients to develop the model and the other half to validate it by comparing predicted vs actual proportions who met the criteria for 4 current stroke trials. The predicted proportion of patients meeting inclusion criteria ranged from 6% to 28% among the different trials. The proportion of trial-eligible patients predicted from the first half of the data were within 0.4% to 1.4% of the actual proportion of eligible patients. This proportion increased logarithmically with National Institutes of Health Stroke Scale score and time from onset; lowering the baseline limits of the National Institutes of Health Stroke Scale score and extending the treatment window would have the greatest impact on the proportion of patients eligible for a stroke trial. This model helps estimate the proportion of stroke patients eligible for a study based on different upper and lower limits for age, stroke severity, and time to treatment, and it may be a useful tool in clinical trial planning.

Experiences of recruiting to a pilot trial of Cardiac Rehabilitation In patients with Bowel cancer (CRIB) with an embedded process evaluation: lessons learned to improve recruitment.

PubMed

Hubbard, Gill; Campbell, Anna; Davies, Zoe; Munro, Julie; Ireland, Aileen V; Leslie, Stephen; Watson, Angus Jm; Treweek, Shaun

2015-01-01

Recruitment to randomised controlled trials (RCTs) is a perennial problem. Calls have been made for trialists to make recruitment performance publicly available. This article presents our experience of recruiting to a pilot RCT of cardiac rehabilitation for patients with bowel cancer with an embedded process evaluation. Recruitment took place at three UK hospitals. Recruitment figures were based on the following: i) estimated number of patient admissions, ii) number of patients likely to meet inclusion criteria from clinician input and iii) recruitment rates in previous studies. The following recruitment procedure was used:Nurse assessed patients for eligibility.Patients signed a screening form indicating interest in and agreement to be approached by a researcher about the study.An appointment was made at which the patient signed a consent form and was randomised to the intervention or control group. Information about all patients considered for the study and subsequently included or excluded at each stage of the recruitment process and reasons given were recorded. There were variations in the time taken to award Research Management approval to run the study at the three sites (45-359 days). Sixty-two percent of the original recruitment estimate was reached. The main reason for under-recruitment was due to over-estimation of the number of patient admissions; other reasons were i) not assessing all patients for eligibility, ii) not completing a screening form for eligible patients and iii) patients who signed a screening form being lost to the study before consenting and randomisation. Pilot trials should not simply aim to improve recruitment estimates but should also identify factors likely to influence recruitment performance in a future trial and inform the development of that trial's recruitment strategies. Pilot trials are a crucial part of RCT design. Nevertheless, pilot trials are likely to be small scale, involving only a small number of sites, and contextual differences between sites are likely to impact recruitment performance in any future trial. This means that ongoing monitoring and evaluation in trials are likely to be required. ISRCTN63510637; UKCRN id 14092.

Risk of bias and methodological issues in randomised controlled trials of acupuncture for knee osteoarthritis: a cross-sectional study

PubMed Central

Lee, Andy H; Zhou, Xu; Kang, Deying; Luo, Yanan; Liu, Jiali; Sun, Xin

2018-01-01

Objective To assess risk of bias and to investigate methodological issues concerning the design, conduct and analysis of randomised controlled trials (RCTs) testing acupuncture for knee osteoarthritis (KOA). Methods PubMed, EMBASE, Cochrane Central Register of Controlled Trials and four major Chinese databases were searched for RCTs that investigated the effect of acupuncture for KOA. The Cochrane tool was used to examine the risk of bias of eligible RCTs. Their methodological details were examined using a standardised and pilot-tested questionnaire of 48 items, together with the association between four predefined factors and important methodological quality indicators. Results A total of 248 RCTs were eligible, of which 39 (15.7%) used computer-generated randomisation sequence. Of the 31 (12.5%) trials that stated the allocation concealment, only one used central randomisation. Twenty-five (10.1%) trials mentioned that their acupuncture procedures were standardised, but only 18 (7.3%) specified how the standardisation was achieved. The great majority of trials (n=233, 94%) stated that blinding was in place, but 204 (87.6%) did not clarify who was blinded. Only 27 (10.9%) trials specified the primary outcome, for which 7 used intention-to-treat analysis. Only 17 (6.9%) trials included details on sample size calculation; none preplanned an interim analysis and associated stopping rule. In total, 46 (18.5%) trials explicitly stated that loss to follow-up occurred, but only 6 (2.4%) provided some information to deal with the issue. No trials prespecified, conducted or reported any subgroup or adjusted analysis for the primary outcome. Conclusion The overall risk of bias was high among published RCTs testing acupuncture for KOA. Methodological limitations were present in many important aspects of design, conduct and analyses. These findings inform the development of evidence-based methodological guidance for future trials assessing the effect of acupuncture for KOA. PMID:29511016

Dose-dense weekly chemotherapy in advanced ovarian cancer: An updated meta-analysis of randomized controlled trials.

PubMed

Marchetti, C; De Felice, F; Di Pinto, A; D'Oria, O; Aleksa, N; Musella, A; Palaia, I; Muzii, L; Tombolini, V; Benedetti Panici, P

2018-05-01

The use of dose-dense weekly chemotherapy in the management of advanced ovarian cancer (OC) remains controversial. The aim of this meta-analysis was to evaluate the efficacy of dose-dense regimen to improve clinical outcomes in OC patients with the inclusion of new trials. For this updated meta-analysis, PubMed Medline and Scopus databases and meeting proceedings were searched for eligible studies with the limitation of randomized controlled trials, comparing dose-dense chemotherapy versus standard treatment. Trials were grouped in two types of dose-dense chemotherapy: weekly dose-dense (both paclitaxel and carboplatin weekly administration) and semi-weekly dose-dense (weekly paclitaxel and three weekly carboplatin administration). Data were extracted independently and were analyzed using RevMan statistical software version 5.3 (http://www.cochrane.org). Primary end-point was progression-free survival (PFS). Four randomized controlled trials comprising 3698 patients were identified as eligible. Dose-dense chemotherapy had not a significant benefit on PFS (HR 0.92, 95% CI 0.81-1.04, p = 0.20). When the analysis was restricted to both weekly and semi-weekly dose-dense data, a no significant interaction between dose-dense and standard regimen was confirmed (HR 1.01, 95% CI 0.93-1.10 and HR 0.82, 95% CI 0.63-1.08, respectively). In the absence of PFS superiority of dose-dense schedule, three weekly schedule should remain the standard of care for advanced OC. Copyright © 2018 Elsevier B.V. All rights reserved.

Pilot study of a point-of-use decision support tool for cancer clinical trials eligibility.

PubMed

Breitfeld, P P; Weisburd, M; Overhage, J M; Sledge, G; Tierney, W M

1999-01-01

Many adults with cancer are not enrolled in clinical trials because caregivers do not have the time to match the patient's clinical findings with varying eligibility criteria associated with multiple trials for which the patient might be eligible. The authors developed a point-of-use portable decision support tool (DS-TRIEL) to automate this matching process. The support tool consists of a hand-held computer with a programmable relational database. A two-level hierarchic decision framework was used for the identification of eligible subjects for two open breast cancer clinical trials. The hand-held computer also provides protocol consent forms and schemas to further help the busy oncologist. This decision support tool and the decision framework on which it is based could be used for multiple trials and different cancer sites.

Pilot Study of a Point-of-use Decision Support Tool for Cancer Clinical Trials Eligibility

PubMed Central

Breitfeld, Philip P.; Weisburd, Marina; Overhage, J. Marc; Sledge, George; Tierney, William M.

1999-01-01

Many adults with cancer are not enrolled in clinical trials because caregivers do not have the time to match the patient's clinical findings with varying eligibility criteria associated with multiple trials for which the patient might be eligible. The authors developed a point-of-use portable decision support tool (DS-TRIEL) to automate this matching process. The support tool consists of a hand-held computer with a programmable relational database. A two-level hierarchic decision framework was used for the identification of eligible subjects for two open breast cancer clinical trials. The hand-held computer also provides protocol consent forms and schemas to further help the busy oncologist. This decision support tool and the decision framework on which it is based could be used for multiple trials and different cancer sites. PMID:10579605

Initial Readability Assessment of Clinical Trial Eligibility Criteria

PubMed Central

Kang, Tian; Elhadad, Noémie; Weng, Chunhua

2015-01-01

Various search engines are available to clinical trial seekers. However, it remains unknown how comprehensible clinical trial eligibility criteria used for recruitment are to a lay audience. This study initially investigated this problem. Readability of eligibility criteria was assessed according to (i) shallow and lexical characteristics through the use of an established, generic readability metric; (ii) syntactic characteristics through natural language processing techniques; and (iii) health terminological characteristics through an automated comparison to technical and lay health texts. We further stratified clinical trials according to various study characteristics (e.g., source country or study type) to understand potential factors influencing readability. Mainly caused by frequent use of technical jargons, a college reading level was found to be necessary to understand eligibility criteria text, a level much higher than the average literacy level of the general American population. The use of technical jargons should be minimized to simplify eligibility criteria text. PMID:26958204

Eligibility of real-world patients with chemo-refractory, K-RAS wild-type, metastatic colorectal cancer for palliative intent regorafenib monotherapy.

PubMed

Angeles, Arkhjamil; Hung, Wayne; Cheung, Winson Y

2018-06-23

The CORRECT trial demonstrated survival benefits with regorafenib monotherapy in patients with treatment-refractory, metastatic colorectal cancer (mCRC). However, the trial's stringent eligibility criteria for regorafenib may limit its external validity. We aimed to examine treatment attrition rates and eligibility for regorafenib in routine practice. We identified patients at the British Columbia Cancer Agency diagnosed with mCRC who demonstrated disease progression or intolerable toxicity on 2 or more lines of systemic therapy. During the study timeframe, panitumumab and cetuximab were only used in the chemo-refractory setting. Data on clinicopathologic variables and patient outcomes were ascertained and analyzed. Eligibility was determined using the CORRECT trial criteria. A total of 391 patients were identified, among whom only 39% were eligible for regorafenib: 35% in the panitumumab group and 51% in the cetuximab group. The main reasons for ineligibility in all patients were Eastern Cooperative Oncology Group Performance Status (ECOG PS) > 1 (69%), an elevated total bilirubin (21%), and thromboembolic events in the past 6 months (10%). No difference in eligibility for regorafenib was observed between patients previously receiving panitumumab or cetuximab (P = 0.914; 95% CI 0.550-1.951). Kaplan-Meier analyses showed that regorafenib-eligible compared to regorafenib-ineligible patients had an increased median overall survival of 5.3 versus 2.1 months, respectively (P < 0.001). However, Cox proportional hazard analyses showed that only ECOG PS rather than trial eligibility was correlated with outcomes. The strict eligibility criteria disqualify most patients with treatment-refractory mCRC for regorafenib therapy. Future trials should broaden the eligibility criteria to improve external validity.

Improving the wellbeing of staff who work in palliative care settings: A systematic review of psychosocial interventions.

PubMed

Hill, Rebecca C; Dempster, Martin; Donnelly, Michael; McCorry, Noleen K

2016-10-01

Staff in palliative care settings perform emotionally demanding roles which may lead to psychological distress including stress and burnout. Therefore, interventions have been designed to address these occupational risks. To investigate quantitative studies exploring the effectiveness of psychosocial interventions that attempt to improve psychological wellbeing of palliative care staff. A systematic review was conducted according to methodological guidance from UK Centre for Reviews and Dissemination. A search strategy was developed based on the initial scans of palliative care studies. Potentially eligible research articles were identified by searching the following databases: CINAHL, MEDLINE (Ovid), PsycINFO and Web of Science. Two reviewers independently screened studies against pre-set eligibility criteria. To assess quality, both researchers separately assessed the remaining studies using the Quality Assessment Tool for Quantitative Studies. A total of 1786 potentially eligible articles were identified - nine remained following screening and quality assessment. Study types included two randomised controlled trials, two non-randomised controlled trial designs, four one-group pre-post evaluations and one process evaluation. Studies took place in the United States and Canada (5), Europe (3) and Hong Kong (1). Interventions comprised a mixture of relaxation, education, support and cognitive training and targeted stress, fatigue, burnout, depression and satisfaction. The randomised controlled trial evaluations did not improve psychological wellbeing of palliative care staff. Only two of the quasi-experimental studies appeared to show improved staff wellbeing although these studies were methodologically weak. There is an urgent need to address the lack of intervention development work and high-quality research in this area. © The Author(s) 2016.

Design, methods, and baseline characteristics of the Kids' Health Insurance by Educating Lots of Parents (Kids' HELP) trial: a randomized, controlled trial of the effectiveness of parent mentors in insuring uninsured minority children.

PubMed

Flores, Glenn; Walker, Candy; Lin, Hua; Lee, Michael; Fierro, Marco; Henry, Monica; Massey, Kenneth; Portillo, Alberto

2015-01-01

Six million US children have no health insurance, and substantial racial/ethnic disparities exist. The design, methods, and baseline characteristics are described for Kids' Health Insurance by Educating Lots of Parents (Kids' HELP), the first randomized, clinical trial of the effectiveness of Parent Mentors (PMs) in insuring uninsured minority children. Latino and African-American children eligible for but not enrolled in Medicaid/CHIP were randomized to PMs, or a control group receiving traditional Medicaid/CHIP outreach. PMs are experienced parents with ≥1 Medicaid/CHIP-covered children. PMs received two days of training, and provide intervention families with information on Medicaid/CHIP eligibility, assistance with application submission, and help maintaining coverage. Primary outcomes include obtaining health insurance, time interval to obtain coverage, and parental satisfaction. A blinded assessor contacts subjects monthly for one year to monitor outcomes. Of 49,361 candidates screened, 329 fulfilled eligibility criteria and were randomized. The mean age is seven years for children and 32 years for caregivers; 2/3 are Latino, 1/3 are African-American, and the mean annual family income is $21,857. Half of caregivers were unaware that their uninsured child is Medicaid/CHIP eligible, and 95% of uninsured children had prior insurance. Fifteen PMs completed two-day training sessions. All PMs are female and minority, 60% are unemployed, and the mean annual family income is $20,913. Post-PM-training, overall knowledge/skills test scores significantly increased, and 100% reported being very satisfied/satisfied with the training. Kids' HELP successfully reached target populations, met participant enrollment goals, and recruited and trained PMs. Copyright © 2014 Elsevier Inc. All rights reserved.

Design, methods, and baseline characteristics of the Kids’ Health Insurance by Educating Lots of Parents (Kids’ HELP) trial: A randomized, controlled trial of the effectiveness of parent mentors in insuring uninsured minority children✰

PubMed Central

Flores, Glenn; Walker, Candy; Lin, Hua; Lee, Michael; Fierro, Marco; Henry, Monica; Massey, Kenneth; Portillo, Alberto

2014-01-01

Background & objectives Six million US children have no health insurance, and substantial racial/ethnic disparities exist. The design, methods, and baseline characteristics are described for Kids’ Health Insurance by Educating Lots of Parents (Kids’ HELP), the first randomized, clinical trial of the effectiveness of Parent Mentors (PMs) in insuring uninsured minority children. Methods & research design Latino and African-American children eligible for but not enrolled in Medicaid/CHIP were randomized to PMs, or a control group receiving traditional Medicaid/CHIP outreach. PMs are experienced parents with ≥ 1 Medicaid/CHIP-covered children. PMs received two days of training, and provide intervention families with information on Medicaid/CHIP eligibility, assistance with application submission, and help maintaining coverage. Primary outcomes include obtaining health insurance, time interval to obtain coverage, and parental satisfaction. A blinded assessor contacts subjects monthly for one year to monitor outcomes. Results Of 49,361 candidates screened, 329 fulfilled eligibility criteria and were randomized. The mean age is seven years for children and 32 years for caregivers; 2/3 are Latino, 1/3 are African-American, and the mean annual family income is $21,857. Half of caregivers were unaware that their uninsured child is Medicaid/CHIP eligible, and 95% of uninsured children had prior insurance. Fifteen PMs completed two-day training sessions. All PMs are female and minority, 60% are unemployed, and the mean annual family income is $20,913. Post-PM-training, overall knowledge/skills test scores significantly increased, and 100% reported being very satisfied/satisfied with the training. Conclusions Kids’ HELP successfully reached target populations, met participant enrollment goals, and recruited and trained PMs. PMID:25476583

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

PubMed

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

2014-07-23

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

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.

External validity of the ARISTOTLE trial in real-life atrial fibrillation patients.

PubMed

Hägg, Lovisa; Johansson, Cecilia; Jansson, Jan-Håkan; Johansson, Lars

2014-10-01

Our primary objective was to determine the proportion of patients with atrial fibrillation (AF) eligible for enrollment in a randomized controlled trial for a novel oral anticoagulant, the ARISTOTLE trial. A secondary objective was to describe the reasons for trial ineligibility. We performed a cross-sectional study of an unselected population including 2274 patients in Skellefteå, Sweden with at least one verified episode of AF on or before December 31, 2010. Patients were classified as suitable or unsuitable for anticoagulant treatment according to current guidelines. The enrollment criteria from the ARISTOTLE trial were extracted from the original publication and applied to the population. Among all patients with AF, 1579 were classified as suitable for anticoagulant treatment. Of these, only 658 patients (42%) were eligible for participation in the ARISTOTLE trial. Among the 921 patients ineligible for participation, 498 did not meet the ECG criteria, 272 had psychosocial problems, and in addition, 78 patients were excluded due to both of these criteria. Our study shows that a majority of the patients in an unselected population with AF suitable for anticoagulant treatment were ineligible for participation in the ARISTOTLE trial. The applicability of the ARISTOTLE trial is therefore unknown for a considerable proportion of patients with AF in real life. © 2014 John Wiley & Sons Ltd.

Interventions for preventing and treating hyperthyroidism in pregnancy.

PubMed

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

2010-09-08

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 assess the effects of interventions for preventing or treating hyperthyroidism in pregnant women. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 July 2010). We intended to include randomised controlled trials comparing antithyroid treatments in pregnant women with hyperthyroidism. Two review authors would have assessed trial eligibility and risk of bias, and extracted data. No trials were located. 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 drugs 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.

Contacting authors to retrieve individual patient data: study protocol for a randomized controlled trial.

PubMed

Veroniki, Areti Angeliki; Straus, Sharon E; Ashoor, Huda; Stewart, Lesley A; Clarke, Mike; Tricco, Andrea C

2016-03-15

Individual patient data (IPD) meta-analysis is considered the "gold standard" for exploring the effectiveness of interventions in different subgroups of patients. However, obtaining IPD is time-consuming and contact with the researchers responsible for the original trials is usually required. To date, there are no studies evaluating different strategies to optimize the process for retrieval of IPD from such researchers. Our aim is to examine the impact of providing incentives to the researchers responsible for the trials eligible for a meta-analysis to submit their IPD. We updated our previously published systematic reviews for type 1 diabetes mellitus comparing long- and intermediate-acting insulin regimens (from January 2013 to June 2015) and for Alzheimer's dementia comparing cognitive enhancers (from January 2015 to May 2015). Eligible were randomized controlled trials (RCTs) fulfilling the eligibility criteria of the systematic reviews. We will randomly allocate authors of the reports of these RCTs into an intervention or control group. Those allocated to the intervention group will be contacted by email, mail, and phone, and will be asked to provide the IPD from their RCT and will be given a financial incentive. Those allocated to the control group will be contacted by email, mail, and phone, but will not receive a financial incentive. Our primary outcome will be the proportion of authors who provide the IPD. The secondary outcomes will be the time to return the dataset (defined as the period between the information request and the authors' response with the dataset), and completeness of data. We will compare the response rates in the two groups using the odds ratio and the corresponding 95 % confidence interval. We will also use binary logistic regression and cox regression analyses to examine whether different RCT characteristics, such as study size and sponsor information, influence the probability of providing IPD and the time needed to share the data. This study will determine whether a financial incentive affects response rates when seeking IPD from the original researchers. We will disseminate our findings in an open access scientific journal and present results at national and international conferences. This trial is registered in Clinical Trials.gov, ID number NCT02569411 . Date of registration 5 October 2015.

Standard versus accelerated initiation of renal replacement therapy in acute kidney injury (STARRT-AKI): study protocol for a randomized controlled trial.

PubMed

Smith, Orla M; Wald, Ron; Adhikari, Neill K J; Pope, Karen; Weir, Matthew A; Bagshaw, Sean M

2013-10-05

Acute kidney injury is a common and devastating complication of critical illness, for which renal replacement therapy is frequently needed to manage severe cases. While a recent systematic review suggested that "earlier" initiation of renal replacement therapy improves survival, completed trials are limited due to small size, single-centre status, and use of variable definitions to define "early" renal replacement therapy initiation. This is an open-label pilot randomized controlled trial. One hundred critically ill patients with severe acute kidney injury will be randomly allocated 1:1 to receive "accelerated" initiation of renal replacement therapy or "standard" initiation at 12 centers across Canada. In the accelerated arm, participants will have a venous catheter placed and renal replacement therapy will be initiated within 12 hours of fulfilling eligibility. In the standard initiation arm, participants will be monitored over 7 days to identify indications for renal replacement therapy. For participants in the standard arm with persistent acute kidney injury, defined as a serum creatinine not declining >50% from the value at the time of eligibility, the initiation of RRT will be discouraged unless one or more of the following criteria are fulfilled: serum potassium ≥6.0 mmol/L; serum bicarbonate ≤10 mmol/L; severe respiratory failure (PaO₂/FiO₂<200) or persisting acute kidney injury for ≥72 hours after fulfilling eligibility. The inclusion criteria are designed to identify a population of critically ill adults with severe acute kidney injury who are likely to need renal replacement therapy during their hospitalization, but not immediately. The primary outcome is protocol adherence (>90%). Secondary outcomes include measures of feasibility (proportion of eligible patients enrolled in the trial, proportion of enrolled patients followed to 90 days for assessment of vital status and the need for renal replacement therapy) and safety (occurrence of adverse events). The optimal timing of renal replacement therapy initiation in patients with severe acute kidney injury remains uncertain, representing an important knowledge gap and a priority for high-quality research. This pilot trial is necessary to establish protocol feasibility, confirm the safety of participants and obtain estimated events rates for design of a large definitive trial. NCT01557361.

The efficacy and resource utilization of remifentanil and fentanyl in fast-track coronary artery bypass graft surgery: a prospective randomized, double-blinded controlled, multi-center trial.

PubMed

Cheng, D C; Newman, M F; Duke, P; Wong, D T; Finegan, B; Howie, M; Fitch, J; Bowdle, T A; Hogue, C; Hillel, Z; Pierce, E; Bukenya, D

2001-05-01

We compared (a) the perioperative complications; (b) times to eligibility for, and actual time of the following: extubation, less intense monitoring, intensive care unit (ICU), and hospital discharge; and (c) resource utilization of nursing ratio for patients receiving either a typical fentanyl/isoflurane/propofol regimen or a remifentanil/isoflurane/propofol regimen for fast-track cardiac anesthesia in 304 adults by using a prospective randomized, double-blinded, double-dummy trial. There were no differences in demographic data, or perioperative mortality and morbidity between the two study groups. The mini-mental status examination at postoperative Days 1 to 3 were similar between the two groups. The eligible and actual times for extubation, less intense monitoring, ICU discharge, and hospital discharge were not significantly different. Further analyses revealed no differences in times for extubation and resource utilization after stratification by preoperative risk scores, age, and country. The nurse/patient ratio was similar between the remifentanil/isoflurane/propofol and fentanyl/isoflu-rane/propofol groups during the initial ICU phase and less intense monitoring phase. Increasing preoperative risk scores and older age (>70 yr) were associated with longer times until extubation (eligible), ICU discharge (eligible and actual), and hospital discharge (eligible and actual). Times until extubation (eligible and actual) and less intense monitoring (eligible) were significantly shorter in Canadian patients than United States' patients. However, there was no difference in hospital length of stay in Canadian and United States' patients. We conclude that both anesthesia techniques permit early and similar times until tracheal extubation, less intense monitoring, ICU and hospital discharge, and reduced resource utilization after coronary artery bypass graft surgery. An ultra-short opioid technique was compared with a standard fast-track small-dose opioid technique in coronary artery bypass graft patients in a prospective randomized, double-blinded controlled study. The postoperative recovery and resource utilization, including stratification of preoperative risk score, age, and country, were analyzed.

Neurofeedback, sham neurofeedback, and cognitive-behavioural group therapy in adults with attention-deficit hyperactivity disorder: a triple-blind, randomised, controlled trial.

PubMed

Schönenberg, Michael; Wiedemann, Eva; Schneidt, Alexander; Scheeff, Jonathan; Logemann, Alexander; Keune, Philipp M; Hautzinger, Martin

2017-09-01

Many studies suggest that electroencephalographic (EEG) neurofeedback might be beneficial in the treatment of attention-deficit hyperactivity disorder (ADHD). However, numbers of well controlled studies are low and neurofeedback techniques are regarded as highly controversial. The present trial examined the efficacy (compared with sham neurofeedback) and efficiency (compared with meta-cognitive therapy) of a standard EEG neurofeedback protocol in adults with ADHD. We did a concurrent, triple-blind, randomised, controlled trial using authorised deception in adults with ADHD from one centre (University of Tübingen) in Tübingen, Germany. Participants were eligible if they fulfilled the DSM-IV-TR criteria for ADHD, were aged between 18 years and 60 years, and had no or stable use of medication for at least 2 months with no intention to change. We excluded participants who had comorbid schizophrenia or schizoaffective disorder, bipolar disorder, borderline personality disorder, epilepsy, or traumatic brain injury; substance abuse or dependence; or current or planned other psychological treatment. Those eligible were randomly assigned to three groups: a neurofeedback group which received 30 verum θ-to-β neurofeedback sessions over 15 weeks, a sham neurofeedback group which received 15 sham followed by 15 verum θ-to-β neurofeedback sessions over 15 weeks, or a meta-cognitive group therapy group which received 12 sessions over 12 weeks. Participants were assigned equally to one of the three interventions through a computerised minimisation randomisation procedure stratified by sex, age, and baseline symptom severity of ADHD. Participants were masked as to whether they were receiving neurofeedback or sham neurofeedback, but those receiving meta-cognitive therapy were aware of their treatment. Clinical assessors (ie, those assessing outcomes) and research staff who did the neurofeedback training were masked to participants' randomisation status only for neurofeedback and sham neurofeedback. The primary outcome was symptom score on the Conners' adult ADHD rating scale, assessed before treatment, at midtreatment (after 8 weeks), after treatment (after 16 weeks), and 6 months later. All individuals with at least one observation after randomisation were included in the analyses. This trial is registered with ClinicalTrials.gov, number NCT01883765. Between Feb 1, 2013, and Dec 1, 2015, 761 people were assessed for eligibility. 656 (86%) were excluded and 118 (15%) were eligible for participation in this study. Eligible participants were randomly assigned to neurofeedback (38 [32%]), sham neurofeedback (39 [33%]), or meta-cognitive therapy (41 [35%]). 37 (97%) individuals for neurofeedback, 38 (97%) for sham neurofeedback, and 38 (93%) for meta-cognitive therapy were included in analyses. Self-reported ADHD symptoms decreased substantially for all treatment groups (B=-2·58 [95% CI -3·48 to -1·68]; p<0·0001) between pretreatment and the end of 6 month follow-up, independent of treatment condition (neurofeedback vs sham neurofeedback B=-0·89 [95% CI -2·14 to 0·37], p=0·168; neurofeedback vs meta-cognitive therapy -0·30 [-1·55 to 0·95], p=0·639). No treatment-related or trial-related serious adverse events were reported. Our findings suggest that neurofeedback training is not superior to a sham condition or group psychotherapy. All three treatments were equivalently effective in reducing ADHD symptoms. This first randomised, sham-controlled trial did not show any specific effects of neurofeedback on ADHD symptoms in adults. German Research Foundation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recruitment experience for a pragmatic randomized controlled trial: Using EMR initiatives and minimizing research infrastructure.

PubMed

Joseph, Christine Lm; Ownby, Dennis R; Zoratti, Edward; Johnson, Dayna; Considine, Shannon; Bourgeois, Renee; Melkonian, Christina; Miree, Cheryl; Johnson, Christine Cole; Lu, Mei

2016-01-01

Modernized approaches to multisite randomized controlled trials (RCT) include the use of electronic medical records (EMR) for recruitment, remote data capture (RDC) for multisite data collection, and strategies to reduce the need for research infrastructure. These features facilitate the conduct of pragmatic trials, or trials conducted in "real life" settings. We describe the recruitment experience of an RCT to evaluate a clinic-based intervention targeting urban youth with asthma. Using encounter and prescription databases, a list of potentially-eligible patients was linked to the Epic appointment scheduling system. Patients were enrolled during a scheduled visit and then electronically randomized to a tailored versus generic online intervention. 1146 appointments for 580 eligible patients visiting 5 clinics were identified, of which 45.9% (266/580) were randomized to reach targeted enrollment (n=250). RDC facilitated multisite enrollment. Intervention content was further personalized through real- time entry of asthma medications prescribed at the clinic visit. EMR monitoring helped with recruitment trouble-shooting. Systemic challenges included a system-wide EMR transition and a system-wide reorganization of clinic staffing. Modernized RCTs can accelerate translation of research findings. Electronic initiatives facilitated implementation of this RCT; however, adaptations to recruitment strategies resulted in a more "explanatory" framework. .

Heterogenic control groups in randomized, controlled, analgesic trials of total hip and knee arthroplasty.

PubMed

Karlsen, Anders P; Mathiesen, Ole; Dahl, Jørgen B

2018-03-01

Postoperative analgesic interventions are often tested adjunct to basic non-opioid analgesics in randomized controlled trials (RCTs). Consequently, treatment in control groups, and possible assay sensitivity, differs between trials. We hypothesized that postoperative opioid requirements and pain intensities vary between different control groups in analgesic trials. Control groups from RCTs investigating analgesic interventions after total hip and knee arthroplasty were categorized based on standardized basic analgesic treatment. Morphine consumption 0 to 24 hours postoperatively, and resting pain scores at 6 and 24 hours for subgroups of basic treatments, were compared with ANOVA. In an additional analysis, we compared pain and opioid requirements in trials where a non-steroidal anti-inflammatory drug (NSAID) was administered as an intervention with trial where NSAID was administered in a control group. We included 171 RCTs employing 28 different control groups with large variability in pain scores and opioid requirements. Four types of control groups (comprising 78 trials) were eligible for subgroup comparisons. These subgroups received "opioid" alone, "NSAID + opioid", "acetaminophen + opioid", or "NSAID + acetaminophen + opioid", respectively. Morphine consumption and pain scores varied substantially between these groups, with no consistent superior efficacy in any subgroup. Additionally, trials administering NSAID as an intervention demonstrated lower pain scores and opioid requirements than trials where NSAID was administered in a control group. Analgesic treatment in RCT control groups varies considerably. Control groups receiving various combinations of opioid, NSAID and acetaminophen did not differ consistently in pain and opioid requirements. Pain and opioid requirements were lower in trials administering NSAID as an intervention compared with trials administering NSAID in a control group.

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

Current evidence demonstrates similar effects of kilohertz-frequency and low-frequency current on quadriceps evoked torque and discomfort in healthy individuals: a systematic review with meta-analysis.

PubMed

da Silva, Vinicius Zacarias Maldaner; Durigan, João Luiz Quaglioti; Arena, Ross; de Noronha, Marcos; Gurney, Burke; Cipriano, Gerson

2015-01-01

Neuromuscular electrical stimulation (NMES) is widely utilized to enhance muscle performance. However, the optimal NMES waveform with respect to treatment effect has not been established. To investigate the effects of kilohertz-frequency alternating current (KFAC) and low-frequency pulsed current (PC) on quadriceps evoked torque and self-reported discomfort. PubMed, The Cochrane Library, EMBASE, MEDLINE, Physiotherapy Evidence Database (PEDro), SinoMed, ISI Web of Knowledge, and CINAHL were searched for randomized controlled trials (RCTs) and quasi-randomized controlled trials (QRCTs). Two reviewers independently selected potential studies according to the inclusion criteria, extracted data, and assessed methodological quality. Studies were eligible if they compared KFAC versus PC interventions. Studies that included outcome measures for percentage of maximal isometric voluntary contraction (%MIVC) torque and self-reported discomfort level were eligible for evaluation. Seven studies involving 127 individuals were included. The methodological quality of eligible trials was moderate, with a mean of 5 on the 10-point PEDro scale. Overall, PC was no better than KFAC in terms of evoked torque and there was no difference in self-reported discomfort level. KFAC and PC have similar effects on quadriceps evoked torque and self-reported discomfort level in healthy individuals. The small number and overall methodological quality of currently available studies included in this meta-analysis indicate that new RCTs are needed to better determine optimal NMES treatment parameters.

Interventions in sports settings to reduce risky alcohol consumption and alcohol-related harm: a systematic review.

PubMed

Kingsland, Melanie; Wiggers, John H; Vashum, Khanrin P; Hodder, Rebecca K; Wolfenden, Luke

2016-01-21

Elevated levels of risky alcohol consumption and alcohol-related harm have been reported for sportspeople and supporters compared to non-sporting populations. Limited systematic reviews have been conducted to assess the effect of interventions targeting such behaviours. A review was undertaken to determine if interventions implemented in sports settings decreased alcohol consumption and related harms. Studies were included that implemented interventions within sports settings; measured alcohol consumption or alcohol-related injury or violence and were either randomised controlled trials, staggered enrollment trials, stepped-wedged trials, quasi-randomised trials, quasi-experimental trials or natural experiments. Studies without a parallel comparison group were excluded. Studies from both published and grey literature were included. Two authors independently screened potential studies against the eligibility criteria, and two authors independently extracted data from included studies and assessed risk of bias. The results of included studies were synthesised narratively. The title and abstract of 6382 papers and the full text of 45 of these papers were screened for eligibility. Three studies met the inclusion criteria for the review. One of the included studies was a randomised controlled trial (RCT) of a cognitive-behavioural intervention with athletes within an Olympic training facility in the USA. The study reported a significant change in alcohol use between pre-test and follow-up between intervention and control groups. The other two studies were RCTs in community sports clubs in Ireland and Australia. The Australian study found a significant intervention effect for both risky alcohol consumption at sports clubs and overall risk of alcohol-related harm. The Irish study found no significant intervention effect. A limited number of studies have been conducted to assess the effect of interventions implemented in sports settings on alcohol consumption and related harms. While two of the three studies found significant intervention effects, it is difficult to determine the extent to which such effects are generalisable. Further controlled trials are required in this setting. PROSPERO CRD42014001739.

The Kidney and Periodontal Disease (KAPD) study: A pilot randomized controlled trial testing the effect of non-surgical periodontal therapy on chronic kidney disease.

PubMed

Grubbs, Vanessa; Garcia, Faviola; Jue, Bonnie L; Vittinghoff, Eric; Ryder, Mark; Lovett, David; Carrillo, Jacqueline; Offenbacher, Steven; Ganz, Peter; Bibbins-Domingo, Kirsten; Powe, Neil R

2017-02-01

Chronic kidney disease (CKD) remains a prevalent public health problem that disproportionately affects minorities and the poor, despite intense efforts targeting traditional risk factors. Periodontal diseases are common bacterial plaque-induced inflammatory conditions that can respond to treatment and have been implicated as a CKD risk factor. However there is limited evidence that treatment of periodontal disease slows the progression of CKD. We describe the protocol of the Kidney and Periodontal Disease (KAPD) study, a 12-month un-blinded, randomized, controlled pilot trial with two intent-to-treat treatment arms: 1. immediate intensive non-surgical periodontal treatment or 2. rescue treatment with delayed intensive treatment. The goals of this pilot study are to test the feasibility of conducting a larger trial in an ethnically and racially diverse, underserved population (mostly poor and/or low literacy) with both CKD and significant periodontal disease to determine the effect of intensive periodontal treatment on renal and inflammatory biomarkers over a 12-month period. To date, KAPD has identified 634 potentially eligible patients who were invited to in-person screening. Of the 83 (13.1%) of potentially eligible patients who attended in-person screening, 51 (61.4%) were eligible for participation and 46 enrolled in the study. The mean age of participants is 59.2years (range 34 to 73). Twenty of the participants (43.5%) are Black and 22 (47.8%) are Hispanic. Results from the KAPD study will provide needed preliminary evidence of the effectiveness of non-surgical periodontal treatment to slow CKD progression and inform the design future clinical research trials. Copyright © 2016. Published by Elsevier Inc.

Effectiveness of off-the-shelf footwear in reducing foot pain in Australian Department of Veterans' Affairs recipients not eligible for medical grade footwear: study protocol for a randomized controlled trial.

PubMed

Menz, Hylton B; Frescos, Nicoletta; Munteanu, Shannon E

2013-04-23

Foot pain is highly prevalent in older people, and in many cases is associated with wearing inadequate footwear. In Australia, the Department of Veterans' Affairs (DVA) covers the costs of medical grade footwear for veterans who have severe foot deformity. However, there is a high demand for footwear by veterans with foot pain who do not meet this eligibility criterion. Therefore, this article describes the design of a randomized controlled trial to evaluate the effectiveness of low cost, off-the-shelf footwear in reducing foot pain in DVA recipients who are currently not eligible for medical grade footwear. One hundred and twenty DVA clients with disabling foot pain residing in Melbourne, Australia, who are not eligible for medical grade footwear will be recruited from the DVA database, and will be randomly allocated to an intervention group or a 'usual care' control group. The intervention group will continue to receive their usual DVA-subsidized podiatry care in addition to being provided with low-cost, supportive footwear (Dr Comfort®, Vasyli Medical, Labrador, Queensland, Australia). The control group will also continue to receive DVA-subsidized podiatry care, but will not be provided with the footwear until the completion of the study. The primary outcome measure will be pain subscale on the Foot Health Status Questionnaire (FHSQ), measured at baseline and 4, 8, 12 and 16 weeks. Secondary outcome measures measured at baseline and 16 weeks will include the function subscale of the FHSQ, the Manchester Foot Pain and Disability Index, the number of DVA podiatry treatments required during the study period, general health-related quality of life (using the Short Form 12® Version 2.0), the number of falls experienced during the follow-up period, the Timed Up and Go test, the presence of hyperkeratotic lesions (corns and calluses), the number of participants using co-interventions to relieve foot pain, and participants' perception of overall treatment effect. Data will be analyzed using the intention-to-treat principle. This study is the first randomized controlled trial to evaluate the effectiveness of off-the-shelf footwear in reducing foot pain in DVA recipients. The intervention has been pragmatically designed to ensure that the study findings can be implemented into policy and clinical practice if found to be effective. Australian New Zealand Clinical Trials Registry: ACTRN12612000322831.

The effect of intrauterine HCG injection on IVF outcome: a systematic review and meta-analysis.

PubMed

Osman, A; Pundir, J; Elsherbini, M; Dave, S; El-Toukhy, T; Khalaf, Y

2016-09-01

In this systematic review and meta-analysis, the effect of intrauterine HCG infusion before embryo transfer on IVF outcomes (live birth rate, clinical pregnancy rate and spontaneous aboretion rate) was investigated. Searches were conducted on MEDLINE, EMBASE and The Cochrane Library. Randomized studies in women undergoing IVF and intracytoplasmic sperm injection comparing intrauterine HCG administration at embryo transfer compared with no intrauterine HCG were eligible for inclusion. Eight randomized controlled trials were eligible for inclusion in the meta-analysis. A total of 3087 women undergoing IVF and intracytoplasmic sperm injection cycles were enrolled (intrauterine HCG group: n = 1614; control group: n = 1473). No significant difference was found in the live birth rate (RR 1.13; 95% CI 0.84 to 1.53) and spontaneous abortion rate (RR 1.00, 95% CI 0.74 to 1.34) between women who received intrauterine HCG and those who did not receive HCG. Although this review was extensive and included randomized controlled trials, no significant heterogeneity was found, and the overall included numbers are relatively small. In conclusion the current evidence does not support the use of intrauterine HCG administration before embryo transfer. Well-designed multicentre trials are needed to provide robust evidence. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Testing the Efficacy of a Kindergarten Mathematics Intervention by Small Group Size

ERIC Educational Resources Information Center

Clarke, Ben; Doabler, Christian T.; Kosty, Derek; Kurtz Nelson, Evangeline; Smolkowski, Keith; Fien, Hank; Turtura, Jessica

2017-01-01

This study used a randomized controlled trial design to investigate the ROOTS curriculum, a 50-lesson kindergarten mathematics intervention. Ten ROOTS-eligible students per classroom (n = 60) were randomly assigned to one of three conditions: a ROOTS five-student group, a ROOTS two-student group, and a no-treatment control group. Two primary…

Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data.

PubMed

Martineau, Adrian R; Jolliffe, David A; Hooper, Richard L; Greenberg, Lauren; Aloia, John F; Bergman, Peter; Dubnov-Raz, Gal; Esposito, Susanna; Ganmaa, Davaasambuu; Ginde, Adit A; Goodall, Emma C; Grant, Cameron C; Griffiths, Christopher J; Janssens, Wim; Laaksi, Ilkka; Manaseki-Holland, Semira; Mauger, David; Murdoch, David R; Neale, Rachel; Rees, Judy R; Simpson, Steve; Stelmach, Iwona; Kumar, Geeta Trilok; Urashima, Mitsuyoshi; Camargo, Carlos A

2017-02-15

Objectives  To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect. Design  Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials. Data sources  Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015. Eligibility criteria for study selection  Randomised, double blind, placebo controlled trials of supplementation with vitamin D 3 or vitamin D 2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome. Results  25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality. Conclusions  Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit. Systematic review registration  PROSPERO CRD42014013953. 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.

Comparative Efficacy of Tongxinluo Capsule and Beta-Blockers in Treating Angina Pectoris: Meta-Analysis of Randomized Controlled Trials.

PubMed

Jia, Yongliang; Leung, Siu-wai

2015-11-01

There have been no systematic reviews, let alone meta-analyses, of randomized controlled trials (RCTs) comparing tongxinluo capsule (TXL) and beta-blockers in treating angina pectoris. This study aimed to evaluate the efficacy of TXL and beta-blockers in treating angina pectoris by a meta-analysis of eligible RCTs. The RCTs comparing TXL with beta-blockers (including metoprolol) in treating angina pectoris were searched and retrieved from databases including PubMed, Chinese National Knowledge Infrastructure, and WanFang Data. Eligible RCTs were selected according to prespecified criteria. Meta-analysis was performed on the odds ratios (OR) of symptomatic and electrocardiographic (ECG) improvements after treatment. Subgroup analysis, sensitivity analysis, meta-regression, and publication biases analysis were conducted to evaluate the robustness of the results. Seventy-three RCTs published between 2000 and 2014 with 7424 participants were eligible. Overall ORs comparing TXL with beta-blockers were 3.40 (95% confidence interval [CI], 2.97-3.89; p<0.0001) for symptomatic improvement and 2.63 (95% CI, 2.29-3.02; p<0.0001) for ECG improvement. Subgroup analysis and sensitivity analysis found no statistically significant dependence of overall ORs on specific study characteristics except efficacy criteria. Meta-regression found no significant except sample sizes for data on symptomatic improvement. Publication biases were statistically significant. TXL seems to be more effective than beta-blockers in treating angina pectoris, on the basis of the eligible RCTs. Further RCTs are warranted to reduce publication bias and verify efficacy.

Nitrous oxide for pain management of first trimester surgical abortion -- a randomized controlled pilot study.

PubMed

Singh, Rameet H; Espey, Eve; Carr, Shannon; Pereda, Brenda; Ogburn, Tony; Leeman, Lawrence

2015-02-01

The objective was to determine feasibility of a study comparing mean pain scores between women randomized to nitrous oxide/oxygen (NO) versus oxygen+oral analgesics for trimester surgical abortion. Pilot randomized controlled trial comparing NO (n=10) versus oxygen+oral analgesics (n=10). Feasibility of subject recruitment, and pain and satisfaction scores on a visual analog scale were evaluated. Fifty-seven percent of eligible women participated. Mean pain scores were similar between groups, and mean satisfaction scores were higher for the NO group (77.5 vs. 46.7, P=.048). The majority of eligible women agreed to participate in this study evaluating an uncommon pain control intervention. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluating an audit and feedback intervention for reducing antibiotic prescribing behaviour in general dental practice (the RAPiD trial): a partial factorial cluster randomised trial protocol

PubMed Central

2014-01-01

Background Antibiotic prescribing in dentistry accounts for 9% of total antibiotic prescriptions in Scottish primary care. The Scottish Dental Clinical Effectiveness Programme (SDCEP) published guidance in April 2008 (2nd edition, August 2011) for Drug Prescribing in Dentistry, which aims to assist dentists to make evidence-based antibiotic prescribing decisions. However, wide variation in prescribing persists and the overall use of antibiotics is increasing. Methods RAPiD is a 12-month partial factorial cluster randomised trial conducted in NHS General Dental Practices across Scotland. Its aim is to compare the effectiveness of individualised audit and feedback (A&F) strategies for the translation into practice of SDCEP recommendations on antibiotic prescribing. The trial uses routinely collected electronic healthcare data in five aspects of its design in order to: identify the study population; apply eligibility criteria; carry out stratified randomisation; generate the trial intervention; analyse trial outcomes. Eligibility was determined on contract status and a minimum level of recent NHS treatment provision. All eligible dental practices in Scotland were simultaneously randomised at baseline either to current audit practice or to an intervention group. Randomisation was stratified by single-handed/multi-handed practices. General dental practitioners (GDPs) working at intervention practices will receive individualised graphical representations of their antibiotic prescribing rate from the previous 14 months at baseline and an update at six months. GDPs could not be blinded to their practice allocation. Intervention practices were further randomised using a factorial design to receive feedback with or without: a health board comparator; a supplementary text-based intervention; additional feedback at nine months. The primary outcome is the total antibiotic prescribing rate per 100 courses of treatment over the year following delivery of the baseline intervention. A concurrent qualitative process evaluation will apply theory-based approaches using the Consolidated Framework for Implementation Research to explore the acceptability of the interventions and the Theoretical Domains Framework to identify barriers and enablers to evidence-based antibiotic prescribing behaviour by GDPs. Discussion RAPiD will provide a robust evaluation of A&F in dentistry in Scotland. It also demonstrates that linked administrative datasets have the potential to be used efficiently and effectively across all stages of an randomised controlled trial. Trial registration Current Controlled Trials ISRCTN49204710 PMID:24758164

Effect of antidepressants and psychological therapies, including hypnotherapy, in irritable bowel syndrome: systematic review and meta-analysis.

PubMed

Ford, Alexander C; Quigley, Eamonn M M; Lacy, Brian E; Lembo, Anthony J; Saito, Yuri A; Schiller, Lawrence R; Soffer, Edy E; Spiegel, Brennan M R; Moayyedi, Paul

2014-09-01

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. Evidence relating to the treatment of this condition with antidepressants and psychological therapies continues to accumulate. We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Trials recruiting adults with IBS, which compared antidepressants with placebo, or psychological therapies with control therapy or "usual management," were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). The search strategy identified 3,788 citations. Forty-eight RCTs were eligible for inclusion: thirty-one compared psychological therapies with control therapy or "usual management," sixteen compared antidepressants with placebo, and one compared both psychological therapy and antidepressants with placebo. Ten of the trials of psychological therapies, and four of the RCTs of antidepressants, had been published since our previous meta-analysis. The RR of IBS symptom not improving with antidepressants vs. placebo was 0.67 (95% CI=0.58-0.77), with similar treatment effects for both tricyclic antidepressants and selective serotonin reuptake inhibitors. The RR of symptoms not improving with psychological therapies was 0.68 (95% CI=0.61-0.76). Cognitive behavioral therapy, hypnotherapy, multicomponent psychological therapy, and dynamic psychotherapy were all beneficial. Antidepressants and some psychological therapies are effective treatments for IBS. Despite the considerable number of studies published in the intervening 5 years since we last examined this issue, the overall summary estimates of treatment effect have remained remarkably stable.

Efficacy and effectiveness of tumour necrosis factor inhibitors in the treatment of rheumatoid arthritis in randomized controlled trials and routine clinical practice.

PubMed

Aaltonen, Kalle J; Ylikylä, Suvi; Tuulikki Joensuu, Jaana; Isomäki, Pia; Pirilä, Laura; Kauppi, Markku; Rannio, Tuomas; Eklund, Kari; Blom, Marja; Nordström, Dan

2017-05-01

Efficacy of TNF inhibitors in the treatment of RA assessed in randomized controlled trials (RCTs) may not be fully comparable to routine care owing to the stringent inclusion criteria. The objective of this study was to observe the effectiveness of TNF inhibitors in real-world patients and assess the patients' potential eligibility for the RCTs. RA patients starting a TNF-inhibitor treatment between 2004 and 2014 were identified from the National Register for Biologic Treatment in Finland, which is a longitudinal observational cohort study. Effectiveness was measured using the ACR and EULAR response criteria and by studying the proportion of patients reaching DAS28 remission. The patients' baseline characteristics were compared against the inclusion criteria of 27 RCTs. EULAR moderate and good treatment responses at 6 months were achieved by 69 and 40% of the users of the first TNF inhibitor, respectively. ACR20, ACR50 and ACR70 responses were reached by 48, 27 and 13%, respectively. DAS28 remission was reached by 47%. Only 7.6-44% of the patients would have been potentially eligible for the RCTs. The eligible patients had better treatment responses compared with the non-eligible patients. Different TNF inhibitors were mostly equipotent, but the usage of MTX co-therapy had a major influence on treatment response. Only a small proportion of patients would have been eligible for RCTs, and the efficacy of TNF inhibitors assessed in them cannot be generalized directly into Finnish routine health 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

Comparison of Survival Outcomes Among Cancer Patients Treated In and Out of Clinical Trials

PubMed Central

2014-01-01

Background Clinical trials test the efficacy of a treatment in a select patient population. We examined whether cancer clinical trial patients were similar to nontrial, “real-world” patients with respect to presenting characteristics and survival. Methods We reviewed the SWOG national clinical trials consortium database to identify candidate trials. Demographic factors, stage, and overall survival for patients in the standard arms were compared with nontrial control subjects selected from the Surveillance, Epidemiology, and End Results program. Multivariable survival analyses using Cox regression were conducted. The survival functions from aggregate data across all studies were compared separately by prognosis (≥50% vs <50% average 2-year survival). All statistical tests were two-sided. Results We analyzed 21 SWOG studies (11 good prognosis and 10 poor prognosis) comprising 5190 patients enrolled from 1987 to 2007. Trial patients were younger than nontrial patients (P < .001). In multivariable analysis, trial participation was not associated with improved overall survival for all 11 good-prognosis studies but was associated with better survival for nine of 10 poor-prognosis studies (P < .001). The impact of trial participation on overall survival endured for only 1 year. Conclusions Trial participation was associated with better survival in the first year after diagnosis, likely because of eligibility criteria that excluded higher comorbidity patients from trials. Similar survival patterns between trial and nontrial patients after the first year suggest that trial standard arm outcomes are generalizable over the long term and may improve confidence that trial treatment effects will translate to the real-world setting. Reducing eligibility criteria would improve access to clinical trials. PMID:24627276

Feasibility of feature-based indexing, clustering, and search of clinical trials: A case study of breast cancer trials from ClinicalTrials.gov

PubMed Central

Boland, Mary Regina; Miotto, Riccardo; Gao, Junfeng; Weng, Chunhua

2013-01-01

Summary Background When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. Objectives This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. Methods We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. Results We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. Conclusions It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency. PMID:23666475

Feasibility of feature-based indexing, clustering, and search of clinical trials. A case study of breast cancer trials from ClinicalTrials.gov.

PubMed

Boland, M R; Miotto, R; Gao, J; Weng, C

2013-01-01

When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency.

Theory-based behavioral intervention increases self-reported physical activity in South African men: a cluster-randomized controlled trial.

PubMed

Jemmott, John B; Jemmott, Loretta S; Ngwane, Zolani; Zhang, Jingwen; Heeren, G Anita; Icard, Larry D; O'Leary, Ann; Mtose, Xoliswa; Teitelman, Anne; Carty, Craig

2014-07-01

To determine whether a health-promotion intervention increases South African men's adherence to physical-activity guidelines. We utilized a cluster-randomized controlled trial design. Eligible clusters, residential neighborhoods near East London, South Africa, were matched in pairs. Within randomly selected pairs, neighborhoods were randomized to theory-based, culturally congruent health-promotion intervention encouraging physical activity or attention-matched HIV/STI risk-reduction control intervention. Men residing in the neighborhoods and reporting coitus in the previous 3 months were eligible. Primary outcome was self-reported individual-level adherence to physical-activity guidelines averaged over 6-month and 12-month post-intervention assessments. Data were collected in 2007-2010. Data collectors, but not facilitators or participants, were blind to group assignment. Primary outcome intention-to-treat analysis included 22 of 22 clusters and 537 of 572 men in the health-promotion intervention and 22 of 22 clusters and 569 of 609 men in the attention-control intervention. Model-estimated probability of meeting physical-activity guidelines was 51.0% in the health-promotion intervention and 44.7% in attention-matched control (OR=1.34; 95% CI, 1.09-1.63), adjusting for baseline prevalence and clustering from 44 neighborhoods. A theory-based culturally congruent intervention increased South African men's self-reported physical activity, a key contributor to deaths from non-communicable diseases in South Africa. ClinicalTrials.gov Identifier: NCT01490359. Copyright © 2014 Elsevier Inc. All rights reserved.

Are large dinners associated with excess weight, and does eating a smaller dinner achieve greater weight loss? A systematic review and meta-analysis.

PubMed

Fong, Mackenzie; Caterson, Ian D; Madigan, Claire D

2017-10-01

There are suggestions that large evening meals are associated with greater BMI. This study reviewed systematically the association between evening energy intake and weight in adults and aimed to determine whether reducing evening intake achieves weight loss. Databases searched were MEDLINE, PubMed, Cinahl, Web of Science, Cochrane Library of Clinical Trials, EMBASE and SCOPUS. Eligible observational studies investigated the relationship between BMI and evening energy intake. Eligible intervention trials compared weight change between groups where the proportion of evening intake was manipulated. Evening intake was defined as energy consumed during a certain time - for example 18.00-21.00 hours - or self-defined meal slots - that is 'dinner'. The search yielded 121 full texts that were reviewed for eligibility by two independent reviewers. In all, ten observational studies and eight clinical trials were included in the systematic review with four and five included in the meta-analyses, respectively. Four observational studies showed a positive association between large evening intake and BMI, five showed no association and one showed an inverse relationship. The meta-analysis of observational studies showed a non-significant trend between BMI and evening intake (P=0·06). The meta-analysis of intervention trials showed no difference in weight change between small and large dinner groups (-0·89 kg; 95 % CI -2·52, 0·75, P=0·29). This analysis was limited by significant heterogeneity, and many trials had an unknown or high risk of bias. Recommendations to reduce evening intake for weight loss cannot be substantiated by clinical evidence, and more well-controlled intervention trials are needed.

Risk of bias and methodological issues in randomised controlled trials of acupuncture for knee osteoarthritis: a cross-sectional study.

PubMed

Jia, Pengli; Tang, Li; Yu, Jiajie; Lee, Andy H; Zhou, Xu; Kang, Deying; Luo, Yanan; Liu, Jiali; Sun, Xin

2018-03-06

To assess risk of bias and to investigate methodological issues concerning the design, conduct and analysis of randomised controlled trials (RCTs) testing acupuncture for knee osteoarthritis (KOA). PubMed, EMBASE, Cochrane Central Register of Controlled Trials and four major Chinese databases were searched for RCTs that investigated the effect of acupuncture for KOA. The Cochrane tool was used to examine the risk of bias of eligible RCTs. Their methodological details were examined using a standardised and pilot-tested questionnaire of 48 items, together with the association between four predefined factors and important methodological quality indicators. A total of 248 RCTs were eligible, of which 39 (15.7%) used computer-generated randomisation sequence. Of the 31 (12.5%) trials that stated the allocation concealment, only one used central randomisation. Twenty-five (10.1%) trials mentioned that their acupuncture procedures were standardised, but only 18 (7.3%) specified how the standardisation was achieved. The great majority of trials (n=233, 94%) stated that blinding was in place, but 204 (87.6%) did not clarify who was blinded. Only 27 (10.9%) trials specified the primary outcome, for which 7 used intention-to-treat analysis. Only 17 (6.9%) trials included details on sample size calculation; none preplanned an interim analysis and associated stopping rule. In total, 46 (18.5%) trials explicitly stated that loss to follow-up occurred, but only 6 (2.4%) provided some information to deal with the issue. No trials prespecified, conducted or reported any subgroup or adjusted analysis for the primary outcome. The overall risk of bias was high among published RCTs testing acupuncture for KOA. Methodological limitations were present in many important aspects of design, conduct and analyses. These findings inform the development of evidence-based methodological guidance for future trials assessing the effect of acupuncture for KOA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A web-based intervention for abused women: the New Zealand isafe randomised controlled trial protocol.

PubMed

Koziol-McLain, Jane; Vandal, Alain C; Nada-Raja, Shyamala; Wilson, Denise; Glass, Nancy E; Eden, Karen B; McLean, Christine; Dobbs, Terry; Case, James

2015-01-31

Intimate partner violence (IPV) and its associated negative mental health consequences are significant for women in New Zealand and internationally. One of the most widely recommended interventions is safety planning. However, few women experiencing violence access specialist services for safety planning. A safety decision aid, weighing the dangers of leaving or staying in an abusive relationship, gives women the opportunity to prioritise, plan and take action to increase safety for themselves and their children. This randomised controlled trial is testing the effectiveness of an innovative, interactive web-based safety decision aid. The trial is an international collaborative concurrent replication of a USA trial (IRIS study NCT01312103), regionalised for the Aotearoa New Zealand culture and offers fully automated online trial recruitment, eligibility screening and consent. In a fully automated web-based trial (isafe) 340 abused women will be randomly assigned in equal numbers to a safety decision aid intervention or usual safety planning control website. Intervention components include: (a) safety priority setting, (b) danger assessment and (c) an individually tailored safety action plan. Self-reported outcome measures are collected at baseline and 3, 6, and 12-months post-baseline. Primary outcomes are depression (measured by Center for Epidemiologic Studies Depression Scale, Revised) and IPV exposure (measured by Severity Violence Against Women Scale) at 12 months post-baseline. Secondary outcomes include PTSD, psychological abuse, decisional conflict, safety behaviors and danger in the relationship. This trial will provide much-needed information on the potential relationships among safety planning, improved mental health, reduced violence as well as decreased decisional conflict related to safety in the abusive relationship. The novel web-based safety decision aid intervention may provide a cost-effective, easily accessed safety-planning resource that can be translated into clinical and community practice by multiple health disciplines and advocates. The trial will also provide information about how women in abusive relationships safely access safety information and resources through the Internet. Finally, the trial will inform other research teams on the feasibility and acceptability of fully automated recruitment, eligibility screening, consent and retention procedures. Trial registered on 03 July 2012 on the Australian New Zealand Clinical Trials Registry ACTRN12612000708853 .

A systematic review of midwife-led interventions to address post partum post-traumatic stress.

PubMed

Borg Cunen, Nicole; McNeill, Jenny; Murray, Karen

2014-02-01

to systematically identify interventions that midwives could introduce to address post-traumatic stress in women following childbirth. a search strategy was developed and relevant papers were identified from databases including Cinahl, Cochrane Library, EMBASE, Maternity and Infant Care, MEDLINE, PsycINFO, and Web of Science. Key search terms used were post-traumatic stress, post partum, intervention, controlled trial and review. Papers eligible for inclusion were primary studies and reviews of research published from 2002-2012, focusing on interventions which could be implemented by midwives for the prevention and/or management of PTSD. For primary studies, RCTs, controlled clinical trials, and cohort studies with a control group were eligible. Eligible reviews were those with a specified search strategy and inclusion/exclusion criteria. Methodological quality was assessed using recognised frameworks. six primary studies and eight reviews were eligible for inclusion. The majority of included studies or reviews focused on debriefing and/or counselling interventions; however the results were not consistent due to significant variation in methodological quality and use of dissimilar interventions. Two of the reviews considered the general management of post partum PTSD and one broadly covered anxiety during pregnancy and the post partum, incorporating a section on PTSD. The majority of women reported that the opportunity to discuss their childbirth experience was subjectively beneficial. no evidence-based midwifery interventions were identified from this systematic review that can be recommended for introduction into practice to address PTSD. It is recommended that future research in this area should incorporate standardised interventions with similar outcome measures to facilitate synthesis of results. Further research on interventions used in non-maternity populations is needed in order to confirm their usefulness in addressing post partum PTSD. © 2013 Elsevier Ltd. All rights reserved.

Can Facebook Be Used for Research? Experiences Using Facebook to Recruit Pregnant Women for a Randomized Controlled Trial

PubMed Central

Adam, Laura M; Manca, Donna P

2016-01-01

Background Recruitment is often a difficult and costly part of any human research study. Social media and other emerging means of mass communication hold promise as means to complement traditional strategies used for recruiting participants because they can reach a large number of people in a short amount of time. With the ability to target a specified audience, paid Facebook advertisements have potential to reach future research participants of a specific demographic. This paper describes the experiences of a randomized controlled trial in Edmonton, Alberta, attempting to recruit healthy pregnant women between 8 and 20 weeks’ gestation for participation in a prenatal study. Various traditional recruitment approaches, in addition to paid Facebook advertisements were trialed. Objective To evaluate the effectiveness of paid advertisements on Facebook as a platform for recruiting pregnant women to a randomized controlled trial in comparison with traditional recruitment approaches. Methods Recruitment using traditional approaches occurred for 7 months, whereas Facebook advertisements ran for a total of 26 days. Interested women were prompted to contact the study staff for a screening call to determine study eligibility. Costs associated with each recruitment approach were recorded and used to calculate the cost to recruit eligible participants. Performance of Facebook advertisements was monitored using Facebook Ads Manager. Results Of the 115 women included, 39.1% (n=45) of the women who contacted study staff heard about the study through Facebook, whereas 60.9% (n=70) of them heard about it through traditional recruitment approaches. During the 215 days (~7 months) that the traditional approaches were used, the average rate of interest was 0.3 (0.2) women/day, whereas the 26 days of Facebook advertisements resulted in an average rate of interest of 2.8 (1.7) women/day. Facebook advertisements cost Can $506.91 with a cost per eligible participant of Cad $20.28. In comparison, the traditional approaches cost Cad $1087, with approximately Cad $24.15 per eligible participant. Demographic characteristics of women were similar between the 2 recruitment methods except that women recruited using Facebook were significantly earlier in their pregnancy than those recruited using traditional approaches (P<.03). Conclusions Paid Facebook advertisements hold promise as a platform for reaching pregnant women. The relative ease of placing an advertisement, the comparable cost per participant recruited, and the dramatically improved recruitment rates in comparison with traditional approaches highlight the importance of combining novel and traditional recruitment approaches to recruit women for pregnancy-related studies. Trial Registration ClinicalTrials.gov NCT02711644; https://clinicaltrials.gov/ct2/show/NCT02711644 (Archived by WebCite at http://www.webcitation.org/6kKpagpMk) PMID:27655184

What Do We Really Know About the Safety of Tai Chi?: A Systematic Review of Adverse Event Reports in Randomized Trials

PubMed Central

Wayne, Peter M.; Berkowitz, Danielle L.; Litrownik, Daniel E.; Buring, Julie E.; Yeh, Gloria Y.

2014-01-01

Objective Systematically review frequency and quality of adverse event (AE) reports in randomized clinical trials (RCTs) of Tai Chi (TC). Data Sources Electronic searches of PubMed/MEDLINE and additional databases from inception through March 2013 of English-language RCTs. Search terms were tai chi, taiji, tai chi chuan. Data were independently extracted by two investigators. Study Selection We included all available randomized controlled trials (RCTs) that were published in English and used Tai Chi as an intervention. Inclusion and exclusion of studies were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data Extraction Eligible RCTs were categorized with respect to AE reporting: 1) No mention of protocols for monitoring AEs or reports of AEs; 2) Reports of AEs either with or without explicit protocols for monitoring AEs. Data Synthesis 153 eligible RCTs were identified, most targeting older adults. Only 50 eligible trials (33%) included reporting of AEs, and of these, only 18 trials (12% overall) also reported an explicit AE monitoring protocol. Protocols varied with respect to rigor of systematic monitoring in both Tai Chi and comparison groups. Reported AEs were typically minor and expected, and primarily musculoskeletal related (e.g., knee and back pain); no intervention-related serious AEs were reported. Conclusions Tai Chi is unlikely to result in serious adverse events, but may be associated with minor musculoskeletal aches and pains. However, poor and inconsistent reporting of AEs greatly limits the conclusions that can be drawn regarding the safety of Tai Chi. PMID:24878398

Why do GPs exclude patients from participating in research? An exploration of adherence to and divergence from trial criteria.

PubMed

Jenkinson, Caroline E; Winder, Rachel E; Sugg, Holly V R; Roberts, Martin J; Ridgway, Nicola; Kuyken, Willem; Wiles, Nicola; Kessler, David; Campbell, John

2014-06-01

The role of GPs in recruiting or excluding participants critically underpins the feasibility, external validity and generalizability of primary care research. A better understanding of this role is needed. To investigate why GPs excluded potentially eligible participants from a large scale randomized controlled trial (RCT), to determine the proportion of patients excluded on account of trial eligibility compared with other reasons, and to explore the impact of such exclusions on the management and generalizability of RCTs. Secondary analysis of data from the CoBalT study, a multi-centre general-practice-based RCT investigating cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression. GPs were asked to screen patient lists generated from computerized record searches for trial eligibility and to provide narrative reasons for excluding patients. These reasons were coded independently by two researchers, with a third researcher resolving discrepancies. Thirty-one percent (4750/15,379) of patients were excluded at the GP screening stage, including 663 on patient lists that remained unscreened. Of the 4087 actively excluded patients, 67% were excluded on account of trial exclusion criteria, 20% for other criteria (half of which were comorbid conditions) and 13% without reason. Clear, comprehensive criteria, particularly with regards to comorbidities, are required for GPs to confidently screen patients for potential participation in research. Future studies should promote inclusivity and encourage GPs to adopt a liberal approach when screening patient lists. This would enhance the validity and generalizability of primary care research and encourage greater patient autonomy. © Crown copyright 2014.

Interventions for preventing and treating hyperthyroidism in pregnancy

PubMed Central

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

2014-01-01

Background 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. Objectives To assess the effects of interventions for preventing or treating hyperthyroidism in pregnant women. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (28 July 2010). Selection criteria We intended to include randomised controlled trials comparing antithyroid treatments in pregnant women with hyperthyroidism. Data collection and analysis Two review authors would have assessed trial eligibility and risk of bias, and extracted data. Main results No trials were located. Authors’ conclusions 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 drugs 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. PMID:20824882

Is clarithromycin a potential treatment for cachexia in people with lung cancer? A feasibility study.

PubMed

Awan, Sarah; Crosby, Vincent; Potter, Vanessa; Hennig, Ivo; Baldwin, David; Ndlovu, Mehluli; Paradine, Sharon; Wilcock, Andrew

2017-02-01

Clarithromycin may improve cachexia and survival in non-small cell lung cancer (NSCLC), but adequately controlled data are lacking. This study was undertaken primarily to inform the feasibility and scale of a phase III trial. Eligible consenting patients with stage IV NSCLC and cachexia were to be randomized to receive either clarithromycin 250mg twice daily or placebo for eight weeks. Aspects of trial feasibility recorded included numbers eligible, approached and recruited, together with adherence and completion of treatment and assessments. Over 6 months, none of 125 patients identified fulfilled the entry criteria. The commonest reasons for ineligibility were the use of an excluded concurrent drug (45, 36%), brain metastases (22, 18%), poor performance status (21, 17%) and current chemotherapy (15, 12%). A phase III trial of clarithromycin using these entry criteria is not feasible in this setting. Other macrolides that have a lower risk of a drug-drug interaction may be more practical to pursue. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

Overcoming recruitment challenges in palliative care clinical trials.

PubMed

LeBlanc, Thomas W; Lodato, Jordan E; Currow, David C; Abernethy, Amy P

2013-11-01

Palliative care is increasingly viewed as a necessary component of cancer care, especially for patients with advanced disease. Rigorous clinical trials are thus needed to build the palliative care evidence base, but clinical research-especially participant recruitment-is difficult. Major barriers include (1) patient factors, (2) "gatekeeping," and (3) ethical concerns. Here we discuss an approach to overcoming these barriers, using the Palliative Care Trial (PCT) as a case study. The PCT was a 2 × 2 × 2 factorial randomized controlled trial (RCT) of different service delivery models to improve pain control in the palliative setting. It used a recruitment protocol that fused evidence-based strategies with principles of "social marketing," an approach involving the systematic application of marketing techniques. Main components included (1) an inclusive triage algorithm, (2) information booklets targeting particular stakeholders, (3) a specialized recruitment nurse, and (4) standardization of wording across all study communications. From an eligible pool of 607 patients, the PCT enrolled 461 patients over 26 months. Twenty percent of patients referred to the palliative care service were enrolled (76% of those eligible after screening). Several common barriers were minimized; among those who declined participation, family disinterest was uncommon (5%), as was the perception of burden imposed (4%). Challenges to clinical trial recruitment in palliative care are significant but not insurmountable. A carefully crafted recruitment and retention protocol can be effective. Our experience with designing and deploying a social-marketing-based protocol shows the benefits of such an approach.

“Smart” RCTs: Development of a Smartphone App for Fully Automated Nutrition-Labeling Intervention Trials

PubMed Central

Li, Nicole; Dunford, Elizabeth; Eyles, Helen; Crino, Michelle; Michie, Jo; Ni Mhurchu, Cliona

2016-01-01

Background There is substantial interest in the effects of nutrition labels on consumer food-purchasing behavior. However, conducting randomized controlled trials on the impact of nutrition labels in the real world presents a significant challenge. Objective The Food Label Trial (FLT) smartphone app was developed to enable conducting fully automated trials, delivering intervention remotely, and collecting individual-level data on food purchases for two nutrition-labeling randomized controlled trials (RCTs) in New Zealand and Australia. Methods Two versions of the smartphone app were developed: one for a 5-arm trial (Australian) and the other for a 3-arm trial (New Zealand). The RCT protocols guided requirements for app functionality, that is, obtaining informed consent, two-stage eligibility check, questionnaire administration, randomization, intervention delivery, and outcome assessment. Intervention delivery (nutrition labels) and outcome data collection (individual shopping data) used the smartphone camera technology, where a barcode scanner was used to identify a packaged food and link it with its corresponding match in a food composition database. Scanned products were either recorded in an electronic list (data collection mode) or allocated a nutrition label on screen if matched successfully with an existing product in the database (intervention delivery mode). All recorded data were transmitted to the RCT database hosted on a server. Results In total approximately 4000 users have downloaded the FLT app to date; 606 (Australia) and 1470 (New Zealand) users met the eligibility criteria and were randomized. Individual shopping data collected by participants currently comprise more than 96,000 (Australia) and 229,000 (New Zealand) packaged food and beverage products. Conclusions The FLT app is one of the first smartphone apps to enable conducting fully automated RCTs. Preliminary app usage statistics demonstrate large potential of such technology, both for intervention delivery and data collection. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12614000964617. New Zealand trial: Australian New Zealand Clinical Trials Registry ACTRN12614000644662. PMID:26988128

Methods for increasing upper airway muscle tonus in treating obstructive sleep apnea: systematic review.

PubMed

Valbuza, Juliana Spelta; de Oliveira, Márcio Moysés; Conti, Cristiane Fiquene; Prado, Lucila Bizari F; de Carvalho, Luciane Bizari Coin; do Prado, Gilmar Fernandes

2010-12-01

Treatment of obstructive sleep apnea (OSA) using methods for increasing upper airway muscle tonus has been controversial and poorly reported. Thus, a review of the evidence is needed to evaluate the effectiveness of these methods. The design used was a systematic review of randomized controlled trials. Data sources are from the Cochrane Library, Medline, Embase and Scielo, registries of ongoing trials, theses indexed at Biblioteca Regional de Medicina/Pan-American Health Organization of the World Health Organization and the reference lists of all the trials retrieved. This was a review of randomized or quasi-randomized double-blind trials on OSA. Two reviewers independently applied eligibility criteria. One reviewer assessed study quality and extracted data, and these processes were checked by a second reviewer. The primary outcome was a decrease in the apnea/hypopnea index (AHI) of below five episodes per hour. Other outcomes were subjective sleep quality, sleep quality measured by night polysomnography, quality of life measured subjectively and adverse events associated with the treatments. Three eligible trials were included. Two studies showed improvements through the objective and subjective analyses, and one study showed improvement of snoring, but not of AHI while the subjective analyses showed no improvement. The adverse events were reported and they were not significant. There is no accepted scientific evidence that methods aiming to increase muscle tonus of the stomatognathic system are effective in reducing AHI to below five events per hour. Well-designed randomized controlled trials are needed to assess the efficacy of such methods.

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.

Computational challenges and human factors influencing the design and use of clinical research participant eligibility pre-screening tools

PubMed Central

2012-01-01

Background Clinical trials are the primary mechanism for advancing clinical care and evidenced-based practice, yet challenges with the recruitment of participants for such trials are widely recognized as a major barrier to these types of studies. Data warehouses (DW) store large amounts of heterogenous clinical data that can be used to enhance recruitment practices, but multiple challenges exist when using a data warehouse for such activities, due to the manner of collection, management, integration, analysis, and dissemination of the data. A critical step in leveraging the DW for recruitment purposes is being able to match trial eligibility criteria to discrete and semi-structured data types in the data warehouse, though trial eligibility criteria tend to be written without concern for their computability. We present the multi-modal evaluation of a web-based tool that can be used for pre-screening patients for clinical trial eligibility and assess the ability of this tool to be practically used for clinical research pre-screening and recruitment. Methods The study used a validation study, usability testing, and a heuristic evaluation to evaluate and characterize the operational characteristics of the software as well as human factors affecting its use. Results Clinical trials from the Division of Cardiology and the Department of Family Medicine were used for this multi-modal evaluation, which included a validation study, usability study, and a heuristic evaluation. From the results of the validation study, the software demonstrated a positive predictive value (PPV) of 54.12% and 0.7%, respectively, and a negative predictive value (NPV) of 73.3% and 87.5%, respectively, for two types of clinical trials. Heuristic principles concerning error prevention and documentation were characterized as the major usability issues during the heuristic evaluation. Conclusions This software is intended to provide an initial list of eligible patients to a clinical study coordinators, which provides a starting point for further eligibility screening by the coordinator. Because this software has a high “rule in” ability, meaning that it is able to remove patients who are not eligible for the study, the use of an automated tool built to leverage an existing enterprise DW can be beneficial to determining eligibility and facilitating clinical trial recruitment through pre-screening. While the results of this study are promising, further refinement and study of this and related approaches to automated eligibility screening, including comparison to other approaches and stakeholder perceptions, are needed and future studies are planned to address these needs. PMID:22646313

Speed of Adoption of Immune Checkpoint Inhibitors of Programmed Cell Death 1 Protein and Comparison of Patient Ages in Clinical Practice vs Pivotal Clinical Trials.

PubMed

O'Connor, Jeremy M; Fessele, Kristen L; Steiner, Jean; Seidl-Rathkopf, Kathi; Carson, Kenneth R; Nussbaum, Nathan C; Yin, Emily S; Adelson, Kerin B; Presley, Carolyn J; Chiang, Anne C; Ross, Joseph S; Abernethy, Amy P; Gross, Cary P

2018-05-10

The US Food and Drug Administration (FDA) is increasing its pace of approvals for novel cancer therapeutics, including for immune checkpoint inhibitors of programmed cell death 1 protein (anti-PD-1 agents). However, little is known about how quickly anti-PD-1 agents reach eligible patients in practice or whether such patients differ from those studied in clinical trials that lead to FDA approval (pivotal clinical trials). To assess the speed with which anti-PD-1 agents reached eligible patients in practice and to compare the ages of patients treated in clinical practice with the ages of those treated in pivotal clinical trials. This retrospective cohort study, performed from January 1, 2011, through August 31, 2016, included patients from the Flatiron Health Network who were eligible for anti-PD-1 treatment of selected cancer types, which included melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). Cumulative proportions of eligible patients receiving anti-PD-1 treatment and their age distributions. The study identified 3089 patients who were eligible for anti-PD-1 treatment (median age, 66 [interquartile range, 56-75] years for patients with melanoma, 66 [interquartile range, 58-72] years for patients with RCC, and 67 [interquartile range, 59-74] years for patients with NSCLC; 1742 male [56.4%] and 1347 [43.6%] female; 2066 [66.9%] white). Of these patients, 2123 (68.7%) received anti-PD-1 treatment, including 439 eligible patients with melanoma (79.1%), 1417 eligible patients with NSCLC (65.6%), and 267 eligible patients with RCC (71.2%). Within 4 months after FDA approval, greater than 60% of eligible patients in each cohort had received anti-PD-1 treatment. Overall, similar proportions of older and younger patients received anti-PD-1 treatment during the first 9 months after FDA approval. However, there were significant differences in age between clinical trial participants and patients receiving anti-PD-1 treatment in clinical practice, with more patients being older than 65 years in clinical practice (range, 327 of 1365 [60.6%] to 46 of 72 [63.9%]) than in pivotal clinical trials (range, 38 of 120 [31.7%] to 223 of 544 [41.0%]; all P < .001). Anti-PD-1 agents rapidly reached patients in clinical practice, and patients treated in clinical practice differed significantly from patients treated in pivotal clinical trials. Future actions are needed to ensure that rapid adoption occurs on the basis of representative trial evidence.

Computational challenges and human factors influencing the design and use of clinical research participant eligibility pre-screening tools.

PubMed

Pressler, Taylor R; Yen, Po-Yin; Ding, Jing; Liu, Jianhua; Embi, Peter J; Payne, Philip R O

2012-05-30

Clinical trials are the primary mechanism for advancing clinical care and evidenced-based practice, yet challenges with the recruitment of participants for such trials are widely recognized as a major barrier to these types of studies. Data warehouses (DW) store large amounts of heterogenous clinical data that can be used to enhance recruitment practices, but multiple challenges exist when using a data warehouse for such activities, due to the manner of collection, management, integration, analysis, and dissemination of the data. A critical step in leveraging the DW for recruitment purposes is being able to match trial eligibility criteria to discrete and semi-structured data types in the data warehouse, though trial eligibility criteria tend to be written without concern for their computability. We present the multi-modal evaluation of a web-based tool that can be used for pre-screening patients for clinical trial eligibility and assess the ability of this tool to be practically used for clinical research pre-screening and recruitment. The study used a validation study, usability testing, and a heuristic evaluation to evaluate and characterize the operational characteristics of the software as well as human factors affecting its use. Clinical trials from the Division of Cardiology and the Department of Family Medicine were used for this multi-modal evaluation, which included a validation study, usability study, and a heuristic evaluation. From the results of the validation study, the software demonstrated a positive predictive value (PPV) of 54.12% and 0.7%, respectively, and a negative predictive value (NPV) of 73.3% and 87.5%, respectively, for two types of clinical trials. Heuristic principles concerning error prevention and documentation were characterized as the major usability issues during the heuristic evaluation. This software is intended to provide an initial list of eligible patients to a clinical study coordinators, which provides a starting point for further eligibility screening by the coordinator. Because this software has a high "rule in" ability, meaning that it is able to remove patients who are not eligible for the study, the use of an automated tool built to leverage an existing enterprise DW can be beneficial to determining eligibility and facilitating clinical trial recruitment through pre-screening. While the results of this study are promising, further refinement and study of this and related approaches to automated eligibility screening, including comparison to other approaches and stakeholder perceptions, are needed and future studies are planned to address these needs.

The feasibility of conducting a randomised controlled trial comparing arthroscopic hip surgery to conservative care for patients with femoroacetabular impingement syndrome: the FASHIoN feasibility study.

PubMed

Griffin, D R; Dickenson, E J; Wall, P D H; Realpe, A; Adams, A; Parsons, N; Hobson, R; Achten, J; Costa, M L; Foster, N E; Hutchinson, C E; Petrou, S; Donovan, J L

2016-10-01

To determine whether it was feasible to perform a randomized controlled trial (RCT) comparing arthroscopic hip surgery to conservative care in patients with femoroacetabular impingement (FAI). This study had two phases: a pre-pilot and pilot RCT. In the pre-pilot, we conducted interviews with clinicians who treated FAI and with FAI patients to determine their views about an RCT. We developed protocols for operative and conservative care. In the pilot RCT, we determined the rates of patient eligibility, recruitment and retention, to investigate the feasibility of the protocol and we established methods to assess treatment fidelity. In the pre-pilot phase, 32 clinicians were interviewed, of which 26 reported theoretical equipoise, but in example scenarios 7 failed to show clinical equipoise. Eighteen patients treated for FAI were also interviewed, the majority of whom felt that surgery and conservative care were acceptable treatments. Surgery was viewed by patients as a 'definitive solution'. Patients were motivated to participate in research but were uncomfortable about randomization. Randomization was more acceptable if the alternative was available at the end of the trial. In the pilot phase, 151 patients were assessed for eligibility. Sixty were eligible and invited to take part in the pilot RCT; 42 consented to randomization. Follow-up was 100% at 12 months. Assessments of treatment fidelity were satisfactory. An RCT to compare arthroscopic hip surgery with conservative care in patients with FAI is challenging but feasible. Recruitment has started for a full RCT.

A Randomized Clinical Trial Comparing Use of Rapid Molecular Testing for Staphylococcus aureus for Patients With Cutaneous Abscesses in the Emergency Department With Standard of Care

PubMed Central

May, Larissa S.; Rothman, Richard E.; Miller, Loren G.; Brooks, Gillian; Zocchi, Mark; Zatorski, Catherine; Dugas, Andrea F.; Ware, Chelsea E.; Jordan, Jeanne A.

2017-01-01

OBJECTIVE To determine whether real-time availability of rapid molecular results of Staphylococcus aureus would impact emergency department clinician antimicrobial selection for adults with cutaneous abscesses. DESIGN We performed a prospective, randomized controlled trial comparing a rapid molecular test with standard of care culture-based testing. Follow-up telephone calls were made at between 2 and 7 days, 1 month, and 3 months after discharge. SETTING Two urban, academic emergency departments. PATIENTS Patients at least 18 years old presenting with a chief complaint of abscess, cellulitis, or insect bite and receiving incision and drainage were eligible. Seven hundred seventy-eight people were assessed for eligibility and 252 met eligibility criteria. METHODS Clinician antibiotic selection and clinical outcomes were evaluated. An ad hoc outcome of test performance was performed. RESULTS We enrolled 252 patients and 126 were randomized to receive the rapid test. Methicillin-susceptible S. aureus–positive patients receiving rapid test results were prescribed beta-lactams more often than controls (absolute difference, 14.5% [95% CI, 1.1%–30.1%]) whereas methicillin-resistant S. aureus–positive patients receiving rapid test results were more often prescribed anti–methicillin-resistant S. aureus antibiotics (absolute difference, 21.5% [95% CI, 10.1%–33.0%]). There were no significant differences between the 2 groups in 1-week or 3-month clinical outcomes. CONCLUSION Availability of rapid molecular test results after incision and drainage was associated with more-targeted antibiotic selection. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01523899 PMID:26306996

Evaluating an audit and feedback intervention for reducing antibiotic prescribing behaviour in general dental practice (the RAPiD trial): a partial factorial cluster randomised trial protocol.

PubMed

Prior, Maria; Elouafkaoui, Paula; Elders, Andrew; Young, Linda; Duncan, Eilidh M; Newlands, Rumana; Clarkson, Jan E; Ramsay, Craig R

2014-04-24

Antibiotic prescribing in dentistry accounts for 9% of total antibiotic prescriptions in Scottish primary care. The Scottish Dental Clinical Effectiveness Programme (SDCEP) published guidance in April 2008 (2nd edition, August 2011) for Drug Prescribing in Dentistry, which aims to assist dentists to make evidence-based antibiotic prescribing decisions. However, wide variation in prescribing persists and the overall use of antibiotics is increasing. RAPiD is a 12-month partial factorial cluster randomised trial conducted in NHS General Dental Practices across Scotland. Its aim is to compare the effectiveness of individualised audit and feedback (A&F) strategies for the translation into practice of SDCEP recommendations on antibiotic prescribing. The trial uses routinely collected electronic healthcare data in five aspects of its design in order to: identify the study population; apply eligibility criteria; carry out stratified randomisation; generate the trial intervention; analyse trial outcomes. Eligibility was determined on contract status and a minimum level of recent NHS treatment provision. All eligible dental practices in Scotland were simultaneously randomised at baseline either to current audit practice or to an intervention group. Randomisation was stratified by single-handed/multi-handed practices. General dental practitioners (GDPs) working at intervention practices will receive individualised graphical representations of their antibiotic prescribing rate from the previous 14 months at baseline and an update at six months. GDPs could not be blinded to their practice allocation. Intervention practices were further randomised using a factorial design to receive feedback with or without: a health board comparator; a supplementary text-based intervention; additional feedback at nine months. The primary outcome is the total antibiotic prescribing rate per 100 courses of treatment over the year following delivery of the baseline intervention. A concurrent qualitative process evaluation will apply theory-based approaches using the Consolidated Framework for Implementation Research to explore the acceptability of the interventions and the Theoretical Domains Framework to identify barriers and enablers to evidence-based antibiotic prescribing behaviour by GDPs. RAPiD will provide a robust evaluation of A&F in dentistry in Scotland. It also demonstrates that linked administrative datasets have the potential to be used efficiently and effectively across all stages of an randomised controlled trial. Current Controlled Trials ISRCTN49204710.

Effects of acupuncture on rates of pregnancy and live birth among women undergoing in vitro fertilisation: systematic review and meta-analysis.

PubMed

Manheimer, Eric; Zhang, Grant; Udoff, Laurence; Haramati, Aviad; Langenberg, Patricia; Berman, Brian M; Bouter, Lex M

2008-03-08

To evaluate whether acupuncture improves rates of pregnancy and live birth when used as an adjuvant treatment to embryo transfer in women undergoing in vitro fertilisation. Systematic review and meta-analysis. Medline, Cochrane Central, Embase, Chinese Biomedical Database, hand searched abstracts, and reference lists. Review methods Eligible studies were randomised controlled trials that compared needle acupuncture administered within one day of embryo transfer with sham acupuncture or no adjuvant treatment, with reported outcomes of at least one of clinical pregnancy, ongoing pregnancy, or live birth. Two reviewers independently agreed on eligibility; assessed methodological quality; and extracted outcome data. For all trials, investigators contributed additional data not included in the original publication (such as live births). Meta-analyses included all randomised patients. Seven trials with 1366 women undergoing in vitro fertilisation were included in the meta-analyses. There was little clinical heterogeneity. Trials with sham acupuncture and no adjuvant treatment as controls were pooled for the primary analysis. Complementing the embryo transfer process with acupuncture was associated with significant and clinically relevant improvements in clinical pregnancy (odds ratio 1.65, 95% confidence interval 1.27 to 2.14; number needed to treat (NNT) 10 (7 to 17); seven trials), ongoing pregnancy (1.87, 1.40 to 2.49; NNT 9 (6 to 15); five trials), and live birth (1.91, 1.39 to 2.64; NNT 9 (6 to 17); four trials). Because we were unable to obtain outcome data on live births for three of the included trials, the pooled odds ratio for clinical pregnancy more accurately represents the true combined effect from these trials rather than the odds ratio for live birth. The results were robust to sensitivity analyses on study validity variables. A prespecified subgroup analysis restricted to the three trials with the higher rates of clinical pregnancy in the control group, however, suggested a smaller non-significant benefit of acupuncture (odds ratio 1.24, 0.86 to 1.77). Current preliminary evidence suggests that acupuncture given with embryo transfer improves rates of pregnancy and live birth among women undergoing in vitro fertilisation.

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

Skin antiseptics in venous puncture site disinfection for preventing blood culture contamination: A Bayesian network meta-analysis of randomized controlled trials.

PubMed

Liu, Wenjie; Duan, Yuchen; Cui, Wenyao; Li, Li; Wang, Xia; Dai, Heling; You, Chao; Chen, Maojun

2016-07-01

To compare the efficacy of several antiseptics in decreasing the blood culture contamination rate. Network meta-analysis. Electronic searches of PubMed and Embase were conducted up to November 2015. Only randomized controlled trials or quasi-randomized controlled trials were eligible. We applied no language restriction. A comprehensive review of articles in the reference lists was also accomplished for possible relevant studies. Relevant studies evaluating efficacy of different antiseptics in venous puncture site for decreasing the blood culture contamination rate were included. The data were extracted from the included randomized controlled trials by two authors independently. The risk of bias was evaluated using Detsky scale by two authors independently. We used WinBUGS1.43 software and statistic model described by Chaimani to perform this network meta-analysis. Then graphs of statistical results of WinBUGS1.43 software were generated using 'networkplot', 'ifplot', 'netfunnel' and 'sucra' procedure by STATA13.0. Odds ratio and 95% confidence intervals were assessed for dichotomous data. A probability of p less than 0.05 was considered to be statistically significant. Compared with ordinary meta-analyses, this network meta-analysis offered hierarchies for the efficacy of different antiseptics in decreasing the blood culture contamination rate. Seven randomized controlled trials involving 34,408 blood samples were eligible for the meta-analysis. No significant difference was found in blood culture contamination rate among different antiseptics. No significant difference was found between non-alcoholic antiseptics and alcoholic antiseptics, alcoholic chlorhexidine and povidone iodine, chlorhexidine and iodine compounds, povidone iodine and iodine tincture in this aspect, respectively. Different antiseptics may not affect the blood culture contamination rate. Different intervals between the skin disinfection and the venous puncture, the different settings (emergency room, medical wards, and intensive care units) and the performance of the phlebotomy may affect the blood culture contamination rate. Copyright © 2016 Elsevier Ltd. All rights reserved.

Understanding the Quality Chasm for Hypertension Control in Diabetes: A Structured Review of “Co-maneuvers” Used in Clinical Trials

PubMed Central

Naik, Aanand D.; Issac, Tim T.; Street, Richard L.; Kunik, Mark E.

2010-01-01

Background Observational studies routinely describe a significant gap between rates of blood pressure control in routine diabetes care compared with those achieved in randomized controlled trials (RCTs). Methods We performed a systematic review of the literature to identify co-maneuvers used in RCTs, defined as ancillary activities or agents administered before, during, or immediately after the main agent under investigation (ie, principal maneuver), but not effectively translated to routine diabetes care. We searched multiple databases for RCTs evaluating the efficacy of treatments for hypertension control in adults with type 2 diabetes mellitus. We considered only phase III human studies of interventions that achieved blood pressure control and scrutinized all elements related to the implementation of the principal maneuver in each candidate study. These elements were then sorted into a taxonomy of co-maneuvers. Results Nearly all eligible RCTs used highly consistent groups of co-maneuvers. These typically began with (1) the use of consensual and clearly stated blood pressure goals; (2) frequent visits in which blood pressure levels were measured and compared with predefined goals; and, if the goal was not attained, (3) modifications to the treatment based on a detailed action plan that included communication of adverse events. Patient education, feedback to clinicians, and interventions for medication adherence were not commonly used among eligible trials. Conclusions Clinicians should translate key behavioral co-maneuvers along with clinically proven treatments for hypertension control in diabetes. These co-maneuvers are conceptually similar to collaborative goal setting and action planning interventions used in innovative chronic care programs. PMID:17823464

Comparative Effectiveness of Phosphate Binders in Patients with Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis.

PubMed

Sekercioglu, Nigar; Thabane, Lehana; Díaz Martínez, Juan Pablo; Nesrallah, Gihad; Longo, Christopher J; Busse, Jason W; Akhtar-Danesh, Noori; Agarwal, Arnav; Al-Khalifah, Reem; Iorio, Alfonso; Guyatt, Gordon H

2016-01-01

Chronic kidney disease-mineral and bone disorder (CKD-MBD) has been linked to poor health outcomes, including diminished quality and length of life. This condition is characterized by high phosphate levels and requires phosphate-lowering agents-phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on patient-important outcomes in patients with CKD-MBD. Data sources included MEDLINE and EMBASE Trials from 1996 to February 2016. We also searched the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD, randomized them to receive calcium (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet, placebo or no treatment, and reported effects on all-cause mortality, cardiovascular mortality or hospitalization at ≥4 weeks follow-up. We performed network meta-analyses (NMA) for all cause-mortality for individual agents (seven-node analysis) and conventional meta-analysis of calcium vs. NCBPBs for all-cause mortality, cardiovascular mortality and hospitalization. In the NMAs, we calculated the effect estimates for direct, indirect and network meta-analysis estimates; for both NMA and conventional meta-analysis, we pooled treatment effects as risk ratios (RR) and calculated 95% confidence intervals (CIs) using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each paired comparison. Our search yielded 1190 citations, of which 71 RCTs were retrieved for full review and 15 proved eligible. With 13 eligible studies from a prior review, we included 28 studies with 8335 participants; 25 trials provided data for our quantitative synthesis. Results suggest higher mortality with calcium than either sevelamer (NMA RR, 1.89 [95% CI, 1.02 to 3.50], moderate quality evidence) or NCBPBs (conventional meta-analysis RR, 1.76 [95% CI, 1.21 to 2.56, moderate quality evidence). Conventional meta-analysis suggested no difference in cardiovascular mortality between calcium and NCBPBs (RR, 2.54 [95% CI, 0.67 to 9.62 low quality evidence). Our results suggest higher hospitalization, although non-significant, with calcium than NCBPBs (RR, 1.293 [95% CI, 0.94 to 1.74, moderate quality evidence). Use of calcium results in higher mortality than either sevelamer in particular and NCBPBs in general (moderate quality evidence). Our results raise questions about whether administration of calcium as an intervention for CKD- MBD remains ethical. Further research is needed to explore the effects of different types of phosphate binders, including novel agents such as iron, on quality and quantity of life. PROSPERO CRD-42016032945.

Challenges of a community based pragmatic, randomised controlled trial of weight loss maintenance.

PubMed

Randell, Elizabeth; McNamara, Rachel; Shaw, Christine; Espinasse, Aude; Simpson, Sharon Anne

2015-12-18

Randomised controlled trials (RCTs) have a reputation for being inherently difficult to deliver as planned and often face unforeseen challenges and delays, particularly in relation to organisational and governance difficulties, participant interest, constraints due to allocation of costs, local investigator interest and lengthy bureaucracy. Recruitment is often difficult and the challenges faced often impact on the cost and delivery of a successful trial within the funded period. This paper reflects upon the challenges faced in delivering a pragmatic RCT of weight loss maintenance in a community setting and suggests some potential solutions. The weight loss maintenance in adults trial aimed to evaluate the impact of a 12 month, individually tailored weight maintenance intervention on BMI 3 years from randomisation. Participants were recruited primarily from participant identification centres (PICs)-GP surgeries, exercise on referral schemes and slimming world. The intervention was delivered in community settings. A recruitment strategy implementation plan was drafted to address and monitor poor recruitment. Delays in opening and recruitment were experienced early on. Some were beyond the control of the study team such as; disagreement over allocation of national health service costs and PIC classification as well as difficulties in securing support from research networks. That the intervention was delivered in community settings was often at the root of these issues. Key items to address at the design stage of future trials include feasibility of eligibility criteria. The most effective element of the recruitment implementation plan was to refocus sources of recruitment and target only those who could fulfil the eligibility criteria immediately. Learnings from this trial should be kept in mind by those designing similar studies in the future. Considering potential governance, cost and research network support implications at the design stage of pragmatic trials of any community-based complex intervention is paramount. The appropriateness and viability of inclusion criteria also require careful consideration as does use of a targeted advertising strategy. ISRCTN35774128, 12/01/2010.

What is the evidence for rest, ice, compression, and elevation therapy in the treatment of ankle sprains in adults?

PubMed

van den Bekerom, Michel P J; Struijs, Peter A A; Blankevoort, Leendert; Welling, Lieke; van Dijk, C Niek; Kerkhoffs, Gino M M J

2012-01-01

Ankle sprains are common problems in acute medical care. The variation in treatment observed for the acutely injured lateral ankle ligament complex in the first week after the injury suggests a lack of evidence-based management strategies for this problem. To analyze the effectiveness of applying rest, ice, compression, and elevation (RICE) therapy begun within 72 hours after trauma for patients in the initial period after ankle sprain. Eligible studies were published original randomized or quasi-randomized controlled trials concerning at least 1 of the 4 subtreatments of RICE therapy in the treatment of acute ankle sprains in adults. MEDLINE, Cochrane Clinical Trial Register, CINAHL, and EMBASE. The lists of references of retrieved publications also were checked manually. We extracted relevant data on treatment outcome (pain, swelling, ankle mobility or range of motion, return to sports, return to work, complications, and patient satisfaction) and assessed the quality of included studies. If feasible, the results of comparable studies were pooled using fixed- or random-effects models. After deduction of the overlaps among the different databases, evaluation of the abstracts, and contact with some authors, 24 potentially eligible trials remained. The full texts of these articles were retrieved and thoroughly assessed as described. This resulted in the inclusion of 11 trials involving 868 patients. The main reason for exclusion was that the authors did not describe a well-defined control group without the intervention of interest. Insufficient evidence is available from randomized controlled trials to determine the relative effectiveness of RICE therapy for acute ankle sprains in adults. Treatment decisions must be made on an individual basis, carefully weighing the relative benefits and risks of each option, and must be based on expert opinions and national guidelines.

Clinical efficacy of preoperative chemotherapy with or without ifosfamide in patients with osteosarcoma of the extremity: meta-analysis of randomized controlled trials.

PubMed

Su, Wenmei; Lai, Zhennan; Wu, Fenping; Lin, Yanming; Mo, Yanli; Yang, Zhixiong; Wu, Jiayuan

2015-02-01

Ifosfamide has been used in neoadjuvant chemotherapy since the mid-1980s. Although several studies have been conducted, the results remain controversial. Randomized controlled trials have an improved balance of confounding factors and reliable results. Thus, we performed a meta-analysis based on randomized controlled trials to gather more evidence of the effect of ifosfamide on neoadjuvant chemotherapy for patients with osteosarcoma of the extremity. An electronic search was conducted via the Internet retrieval system to identify eligible trials until September 2014. Odds ratios (ORs) and 95 % confidence interval (CI) were calculated to compare the results of ifosfamide and ifosfamide-free therapies. Four trials with a total of 1,378 patients were eligible for our meta-analysis. Overall, compared with neoadjuvant chemotherapy without ifosfamide, the use of ifosfamide had no advantage in terms of histological response to chemotherapy (cHR; OR 1.36; 95 % CI 0.90-2.03, P = 0.140), 5-year event-free survival (EFS; OR 1.16; 95 % CI 0.789-1.75, P = 0.464), and 5-year overall survival (OS; OR 1.06; 95 % CI 0.70-1.59, P = 0.794). However, improvement was noted in the rate of limb salvage (OR 4.06; 95 % CI 2.04-8.10, P < 0.001). Neoadjuvant chemotherapy with ifosfamide for patients with extremity osteosarcoma might not increase the cHR and exhibited no significant effect on either EFS or OS. However, ifosfamide therapy could significantly increase the rate of limb salvage for osteosarcoma of the extremity, which suggests that the preoperative use of ifosfamide could increase the success rate of limb salvage operation.

A screening tool to enhance clinical trial participation at a community center involved in a radiation oncology disparities program.

PubMed

Proctor, Julian W; Martz, Elaine; Schenken, Larry L; Rainville, Rebecca; Marlowe, Ursula

2011-05-01

To investigate the effectiveness of a screening tool to enhance clinical trial participation at a community radiation oncology center involved in a National Cancer Institute-funded disparities program but lacking on-site clinical trials personnel. The screening form was pasted to the front of the charts and filled out for all new patients over the 9-month period of the study, during which time five external beam radiation therapy (EBRT) trials and a patient perception study were open for accrual. Patient consent was obtained by assorted personnel at several different sites. Patients potentially eligible for a trial were identified and approached by one of the clinic staff. Patients who were under- or uninsured, age > 80 years, members of an racial/ethnic minority, or recipients of medical assistance were identified as at risk for health care disparities and were offered patient navigator services. Of 196 patients consulted during the study, 144 were treated with EBRT. Of the 24 patients eligible for EBRT trials, 23 were approached (one had an incomplete screening form), and 15 accepted. Of 77 patients eligible for a patient perception trial, 72 were approached (five had incomplete forms), and 45 accepted. The eligibility and acceptance rates for EBRT trials were similar for disparities and nondisparities patients. Screening was completed for 96 patients (67%). When completed, the screening tool ensured clinical trial accrual. The major factor limiting overall accrual was a shortage of available trials.

A Screening Tool to Enhance Clinical Trial Participation at a Community Center Involved in a Radiation Oncology Disparities Program

PubMed Central

Proctor, Julian W.; Martz, Elaine; Schenken, Larry L.; Rainville, Rebecca; Marlowe, Ursula

2011-01-01

Purpose: To investigate the effectiveness of a screening tool to enhance clinical trial participation at a community radiation oncology center involved in a National Cancer Institute–funded disparities program but lacking on-site clinical trials personnel. Patients and Methods: The screening form was pasted to the front of the charts and filled out for all new patients over the 9-month period of the study, during which time five external beam radiation therapy (EBRT) trials and a patient perception study were open for accrual. Patient consent was obtained by assorted personnel at several different sites. Patients potentially eligible for a trial were identified and approached by one of the clinic staff. Patients who were under- or uninsured, age > 80 years, members of an racial/ethnic minority, or recipients of medical assistance were identified as at risk for health care disparities and were offered patient navigator services. Results: Of 196 patients consulted during the study, 144 were treated with EBRT. Of the 24 patients eligible for EBRT trials, 23 were approached (one had an incomplete screening form), and 15 accepted. Of 77 patients eligible for a patient perception trial, 72 were approached (five had incomplete forms), and 45 accepted. The eligibility and acceptance rates for EBRT trials were similar for disparities and nondisparities patients. Screening was completed for 96 patients (67%). Conclusion: When completed, the screening tool ensured clinical trial accrual. The major factor limiting overall accrual was a shortage of available trials. PMID:21886496

Effectiveness, efficiency, duration, and costs of recruiting for an African American women's lifestyle physical activity program.

PubMed

Wilbur, Joellen; Buchholz, Susan W; Ingram, Diana M; Braun, Lynne T; Johnson, Tricia J; Fogg, Louis; Miller, Arlene M; Volgman, Annabelle S; McDevitt, Judith

2013-10-01

In a 48-week lifestyle physical activity controlled trial in African American women, we analyzed recruitment effectiveness, efficiency, duration, and costs. Social networking was the most effective approach for inviting women to the trial. Of the 609 who responded to invitations, 514 completed telephone screening; of these, 409 (80%) were found eligible. The health assessment screening was completed by 337 women; of these, 297 (88%) were found eligible. The mean number of days from completion of the telephone and health assessment screenings to beginning the intervention was 23.01, and the mean cost was $74.57 per person. Results suggest that provision of health assessment screening by study staff as part of recruitment is effective for minimizing attrition and also might be cost-effective. © 2013 Wiley Periodicals, Inc.

77 FR 69812 - Agency Information Collection Activities; Comment Request; DC Choice Evaluation

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-21

... oversubscribed. The study will include the administration of annual academic assessments and surveys of students... randomized control trial comparing outcomes of eligible applicants (students and their parents) assigned by lottery to receive or not receive a scholarship. This design is consistent with the requirement for a...

An explorative analysis of the recruitment of patients to a randomised controlled trial in adolescents with dental anxiety.

PubMed

Wide Boman, Ulla; Broberg, Anders G; Krekmanova, Larisa; Staberg, Marie; Svensson, Carina; Robertson, Agneta

2014-01-01

Randomised controlled trials (RCTs) are considered to provide the most reliable evidence on the efficacy of interventions. The aim of this study was to describe the recruitment process of an RCT study set up to evaluate a Cognitive Behavioural Therapy (CBT) intervention programme for adolescent patients with dental anxiety (DA). The participants were recruited from a consecutive sample of adolescent patients (12-19 yrs old) referred for DA to a specialised pediatric dentistry clinic. Age, gender, and reason for referral were recorded for the possible eligible patients as part of the drop-out analysis of the recruitment process. Participants were then randomized to the intervention (CBT integrated with dental treatment) or control (adapted dental treatment) condition. In the recruitment process, 138 possible eligible patients met inclusion criteria, of these 55 were enrolled, 44 declined participation and 39 patients were excluded.The patients enrolled in the RCT did not differ from the non-participants with regard to age, gender or cause of referral. As a result of difficulties in the recruitment process, the study period was extended. The considerable proportion of non-participants as evident from the recruitment process may pose a threat to the external validity of the clinical trial. From a clinical perspective, the reasons for the lack of motivation to participate in behavioural interventions and the failure to appear warrant further investigation.

The ring vaccination trial: a novel cluster randomised controlled trial design to evaluate vaccine efficacy and effectiveness during outbreaks, with special reference to Ebola.

PubMed

2015-07-27

A World Health Organization expert meeting on Ebola vaccines proposed urgent safety and efficacy studies in response to the outbreak in West Africa. One approach to communicable disease control is ring vaccination of individuals at high risk of infection due to their social or geographical connection to a known case. This paper describes the protocol for a novel cluster randomised controlled trial design which uses ring vaccination.In the Ebola ça suffit ring vaccination trial, rings are randomised 1:1 to (a) immediate vaccination of eligible adults with single dose vaccination or (b) vaccination delayed by 21 days. Vaccine efficacy against disease is assessed in participants over equivalent periods from the day of randomisation. Secondary objectives include vaccine effectiveness at the level of the ring, and incidence of serious adverse events. Ring vaccination trials are adaptive, can be run until disease elimination, allow interim analysis, and can go dormant during inter-epidemic periods. © Ebola ça suffit ring vaccination trial consortium 2015.

Randomised controlled trials of homeopathy in humans: characterising the research journal literature for systematic review.

PubMed

Mathie, Robert T; Hacke, Daniela; Clausen, Jürgen; Nicolai, Ton; Riley, David S; Fisher, Peter

2013-01-01

A new programme of systematic reviews of randomised controlled trials (RCTs) in homeopathy will distinguish important attributes of RCT records, including: placebo controlled versus other-than-placebo (OTP) controlled; individualised versus non-individualised homeopathy; peer-reviewed (PR) versus non peer-reviewed (NPR) sources. (a) To outline the methods used to search and categorise the RCT literature; (b) to report details of the records retrieved; (c) to compare our retrieved records with those reported in two previous systematic reviews (Linde et al., 1997; Shang et al., 2005). Ten major electronic databases were searched for records published up to the end of 2011. A record was accepted for subsequent systematic review if it was a substantive report of a clinical trial of homeopathic treatment or prophylaxis in humans, randomised and controlled, and published in a PR or NPR journal. 489 records were potentially eligible: 226 were rejected as non-journal, minor or repeat publications, or lacking randomisation and/or controls and/or a 'homeopathic' intervention; 263 (164 PR, 99 NPR) were acceptable for systematic review. The 263 accepted records comprised 217 (137 PR, 80 NPR) placebo-controlled RCTs, of which 121 were included by, 66 were published after, and 30 were potentially eligible for, but not listed by, Linde or Shang. The 137 PR records of placebo-controlled RCTs comprise 41 on individualised homeopathy and 96 on non-individualised homeopathy. Our findings clarify the RCT literature in homeopathy. The 263 accepted journal papers will be the basis for our forthcoming programme of systematic reviews. Copyright © 2012 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Factors Associated With Dropout During Recruitment and Follow-Up Periods of a mHealth-Based Randomized Controlled Trial for Mobile.Net to Encourage Treatment Adherence for People With Serious Mental Health Problems.

PubMed

Kannisto, Kati Anneli; Korhonen, Joonas; Adams, Clive E; Koivunen, Marita Hannele; Vahlberg, Tero; Välimäki, Maritta Anneli

2017-02-21

Clinical trials are the gold standard of evidence-based practice. Still many papers inadequately report methodology in randomized controlled trials (RCTs), particularly for mHealth interventions for people with serious mental health problems. To ensure robust enough evidence, it is important to understand which study phases are the most vulnerable in the field of mental health care. We mapped the recruitment and the trial follow-up periods of participants to provide a picture of the dropout predictors from a mHealth-based trial. As an example, we used a mHealth-based multicenter RCT, titled "Mobile.Net," targeted at people with serious mental health problems. Recruitment and follow-up processes of the Mobile.Net trial were monitored and analyzed. Recruitment outcomes were recorded as screened, eligible, consent not asked, refused, and enrolled. Patient engagement was recorded as follow-up outcomes: (1) attrition during short message service (SMS) text message intervention and (2) attrition during the 12-month follow-up period. Multiple regression analysis was used to identify which demographic factors were related to recruitment and retention. We recruited 1139 patients during a 15-month period. Of 11,530 people screened, 36.31% (n=4186) were eligible. This eligible group tended to be significantly younger (mean 39.2, SD 13.2 years, P<.001) and more often women (2103/4181, 50.30%) than those who were not eligible (age: mean 43.7, SD 14.6 years; women: 3633/6514, 55.78%). At the point when potential participants were asked to give consent, a further 2278 refused. Those who refused were a little older (mean 40.2, SD 13.9 years) than those who agreed to participate (mean 38.3, SD 12.5 years; t1842=3.2, P<.001). We measured the outcomes after 12 months of the SMS text message intervention. Attrition from the SMS text message intervention was 4.8% (27/563). The patient dropout rate after 12 months was 0.36% (4/1123), as discovered from the register data. In all, 3.12% (35/1123) of the participants withdrew from the trial. However, dropout rates from the patient survey (either by paper or telephone interview) were 52.45% (589/1123) and 27.8% (155/558), respectively. Almost all participants (536/563, 95.2%) tolerated the intervention, but those who discontinued were more often women (21/27, 78%; P=.009). Finally, participants' age (P<.001), gender (P<.001), vocational education (P=.04), and employment status (P<.001) seemed to predict their risk of dropping out from the postal survey. Patient recruitment and engagement in the 12-month follow-up conducted with a postal survey were the most vulnerable phases in the SMS text message-based trial. People with serious mental health problems may need extra support during the recruitment process and in engaging them in SMS text message-based trials to ensure robust enough evidence for mental health care. International Standard Randomized Controlled Trial Number (ISRCTN): 27704027; http://www.isrctn.com/ISRCTN27704027 (Archived by WebCite at http://www.webcitation.org/6oHcU2SFp). ©Kati Anneli Kannisto, Joonas Korhonen, Clive E Adams, Marita Hannele Koivunen, Tero Vahlberg, Maritta Anneli Välimäki. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 21.02.2017.

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.

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.

Evaluating biomarkers for prognostic enrichment of clinical trials.

PubMed

Kerr, Kathleen F; Roth, Jeremy; Zhu, Kehao; Thiessen-Philbrook, Heather; Meisner, Allison; Wilson, Francis Perry; Coca, Steven; Parikh, Chirag R

2017-12-01

A potential use of biomarkers is to assist in prognostic enrichment of clinical trials, where only patients at relatively higher risk for an outcome of interest are eligible for the trial. We investigated methods for evaluating biomarkers for prognostic enrichment. We identified five key considerations when considering a biomarker and a screening threshold for prognostic enrichment: (1) clinical trial sample size, (2) calendar time to enroll the trial, (3) total patient screening costs and the total per-patient trial costs, (4) generalizability of trial results, and (5) ethical evaluation of trial eligibility criteria. Items (1)-(3) are amenable to quantitative analysis. We developed the Biomarker Prognostic Enrichment Tool for evaluating biomarkers for prognostic enrichment at varying levels of screening stringency. We demonstrate that both modestly prognostic and strongly prognostic biomarkers can improve trial metrics using Biomarker Prognostic Enrichment Tool. Biomarker Prognostic Enrichment Tool is available as a webtool at http://prognosticenrichment.com and as a package for the R statistical computing platform. In some clinical settings, even biomarkers with modest prognostic performance can be useful for prognostic enrichment. In addition to the quantitative analysis provided by Biomarker Prognostic Enrichment Tool, investigators must consider the generalizability of trial results and evaluate the ethics of trial eligibility criteria.

Peer Support for Achieving Independence in Diabetes (Peer-AID): design, methods and baseline characteristics of a randomized controlled trial of community health worker assisted diabetes self-management support.

PubMed

Nelson, Karin; Drain, Nathan; Robinson, June; Kapp, Janet; Hebert, Paul; Taylor, Leslie; Silverman, Julie; Kiefer, Meghan; Lessler, Dan; Krieger, James

2014-07-01

Community health workers (CHWs) may be an important mechanism to provide diabetes self-management to disadvantaged populations. We describe the design and baseline results of a trial evaluating a home-based CHW intervention. Peer Support for Achieving Independence in Diabetes (Peer-AID) is a randomized, controlled trial evaluating a home-based CHW-delivered diabetes self-management intervention versus usual care. The study recruited participants from 3 health systems. Change in A1c measured at 12 months is the primary outcome. Changes in blood pressure, lipids, health care utilization, health-related quality of life, self-efficacy and diabetes self-management behaviors at 12 months are secondary outcomes. A total of 1438 patients were identified by a medical record review as potentially eligible, 445 patients were screened by telephone for eligibility and 287 were randomized. Groups were comparable at baseline on socio-demographic and clinical characteristics. All participants were low-income and were from diverse racial and ethnic backgrounds. The mean A1c was 8.9%, mean BMI was above the obese range, and non-adherence to diabetes medications was high. The cohort had high rates of co-morbid disease and low self-reported health status. Although one-third reported no health insurance, the mean number of visits to a physician in the past year was 5.7. Trial results are pending. Peer-AID recruited and enrolled a diverse group of low income participants with poorly controlled type 2 diabetes and delivered a home-based diabetes self-management program. If effective, replication of the Peer-AID intervention in community based settings could contribute to improved control of diabetes in vulnerable populations. Published by Elsevier Inc.

Peer Support for Achieving Independence in Diabetes (Peer-AID): Design, methods and baseline characteristics of a randomized controlled trial of community health worker assisted diabetes self-management support

PubMed Central

Nelson, Karin; Drain, Nathan; Robinson, June; Kapp, Janet; Hebert, Paul; Taylor, Leslie; Silverman, Julie; Kiefer, Meghan; Lessler, Dan; Krieger, James

2014-01-01

Background & Objectives Community health workers (CHWs) may be an important mechanism to provide diabetes self-management to disadvantaged populations. We describe the design and baseline results of a trial evaluating a home-based CHW intervention. Methods & Research Design Peer Support for Achieving Independence in Diabetes (Peer-AID) is a randomized, controlled trial evaluating a home-based CHW-delivered diabetes self-management intervention versus usual care. The study recruited participants from 3 health systems. Change in A1c measured at 12 months is the primary outcome. Change in blood pressure, lipids, health care utilization, health-related quality of life, self-efficacy and diabetes self-management behaviors at 12 months are secondary outcomes. Results A total of 1,438 patients were identified by medical record review as potentially eligible, 445 patients were screened by telephone for eligibility and 287 were randomized. Groups were comparable at baseline on socio-demographic and clinical characteristics. All participants were low-income and were from diverse racial and ethnic backgrounds. The mean A1c was 8.9%, mean BMI was above the obese range, and non-adherence to diabetes medications was high. The cohort had high rates of co-morbid disease and low self-reported health status. Although one-third reported no health insurance, the mean number of visits to a physician in the past year was 5.7. Trial results are pending. Conclusions Peer-AID recruited and enrolled a diverse group of low income participants with poorly controlled type 2 diabetes and delivered a home-based diabetes self-management program. If effective, replication of the Peer-AID intervention in community based settings could contribute to improved control of diabetes in vulnerable populations. PMID:24956324

Fitness for entering a simple exercise program and mortality: a study corollary to the exercise introduction to enhance performance in dialysis (EXCITE) trial.

PubMed

Baggetta, Rossella; Bolignano, Davide; Torino, Claudia; Manfredini, Fabio; Aucella, Filippo; Barillà, Antonio; Battaglia, Yuri; Bertoli, Silvio; Bonanno, Graziella; Castellino, Pietro; Ciurlino, Daniele; Cupisti, Adamasco; D'Arrigo, Graziella; De Paola, Luciano; Fabrizi, Fabrizio; Fatuzzo, Pasquale; Fuiano, Giorgio; Lombardi, Luigi; Lucisano, Gaetano; Messa, Piergiorgio; Rapanà, Renato; Rapisarda, Francesco; Rastelli, Stefania; Rocca-Rey, Lisa; Summaria, Chiara; Zuccalà, Alessandro; Abd ElHafeez, Samar; Tripepi, Giovanni; Catizone, Luigi; Mallamaci, Francesca; Zoccali, Carmine

2014-01-01

In this corollary analysis of the EXCITE study, we looked at possible differences in baseline risk factors and mortality between subjects excluded from the trial because non-eligible (n=216) or because eligible but refusing to participate (n=116). Baseline characteristics and mortality data were recorded. Survival and independent predictors of mortality were assessed by Kaplan-Meier and Cox regression analyses. The incidence rate of mortality was higher in non-eligible vs. eligible non-randomized patients (21.0 vs. 10.9 deaths/100 persons-year; P<0.001). The crude excess risk of death in non-eligible patients (HR 1.96; 95% CI 1.36 to 2.77; P<0.001) was reduced after adjustment for risk factors which differed in the two cohorts including age, blood pressure, phosphate, CRP, smoking, diabetes, triglycerides, cardiovascular comorbidities and history of neoplasia (HR 1.60; 95% CI 1.10 to 2.35; P=0.017) and almost nullified after including in the same model also information on deambulation impairment (HR 1.16; 95% CI 0.75 to 1.80; P=0.513). Deambulation ability mostly explains the difference in survival rate in non-eligible and eligible non-randomized patients in the EXCITE trial. Extending data analyses and outcome reporting also to subjects not taking part in a trial may be helpful to assess the representability of the study population. © 2014 S. Karger AG, Basel.

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

PubMed

Chongsomchai, Chompilas; Lumbiganon, Pisake; Laopaiboon, Malinee

2014-10-20

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

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.

Impact and Costs of Incentives to Reduce Attrition in Online Trials: Two Randomized Controlled Trials

PubMed Central

Murray, Elizabeth; Kalaitzaki, Eleftheria; White, Ian R; McCambridge, Jim; Thompson, Simon G; Wallace, Paul; Godfrey, Christine

2011-01-01

Background Attrition from follow-up is a major methodological challenge in randomized trials. Incentives are known to improve response rates in cross-sectional postal and online surveys, yet few studies have investigated whether they can reduce attrition from follow-up in online trials, which are particularly vulnerable to low follow-up rates. Objectives Our objective was to determine the impact of incentives on follow-up rates in an online trial. Methods Two randomized controlled trials were embedded in a large online trial of a Web-based intervention to reduce alcohol consumption (the Down Your Drink randomized controlled trial, DYD-RCT). Participants were those in the DYD pilot trial eligible for 3-month follow-up (study 1) and those eligible for 12-month follow-up in the DYD main trial (study 2). Participants in both studies were randomly allocated to receive an offer of an incentive or to receive no offer of an incentive. In study 1, participants in the incentive arm were randomly offered a £5 Amazon.co.uk gift voucher, a £5 charity donation to Cancer Research UK, or entry in a prize draw for £250. In study 2, participants in the incentive arm were offered a £10 Amazon.co.uk gift voucher. The primary outcome was the proportion of participants who completed follow-up questionnaires in the incentive arm(s) compared with the no incentive arm. Results In study 1 (n = 1226), there was no significant difference in response rates between those participants offered an incentive (175/615, 29%) and those with no offer (162/611, 27%) (difference = 2%, 95% confidence interval [CI] –3% to 7%). There was no significant difference in response rates among the three different incentives offered. In study 2 (n = 2591), response rates were 9% higher in the group offered an incentive (476/1296, 37%) than in the group not offered an incentive (364/1295, 28%) (difference = 9%, 95% CI 5% to 12%, P < .001). The incremental cost per extra successful follow-up in the incentive arm was £110 in study 1 and £52 in study 2. Conclusion Whereas an offer of a £10 Amazon.co.uk gift voucher can increase follow-up rates in online trials, an offer of a lower incentive may not. The marginal costs involved require careful consideration. Trial registration ISRCTN31070347; http://www.controlled-trials.com/ISRCTN31070347 (Archived by WebCite at http://www.webcitation.org/5wgr5pl3s) PMID:21371988

Sampling bias in an internet treatment trial for depression.

PubMed

Donkin, L; Hickie, I B; Christensen, H; Naismith, S L; Neal, B; Cockayne, N L; Glozier, N

2012-10-23

Internet psychological interventions are efficacious and may reduce traditional access barriers. No studies have evaluated whether any sampling bias exists in these trials that may limit the translation of the results of these trials into real-world application. We identified 7999 potentially eligible trial participants from a community-based health cohort study and invited them to participate in a randomized controlled trial of an online cognitive behavioural therapy programme for people with depression. We compared those who consented to being assessed for trial inclusion with nonconsenters on demographic, clinical and behavioural indicators captured in the health study. Any potentially biasing factors were then assessed for their association with depression outcome among trial participants to evaluate the existence of sampling bias. Of the 35 health survey variables explored, only 4 were independently associated with higher likelihood of consenting-female sex (odds ratio (OR) 1.11, 95% confidence interval (CI) 1.05-1.19), speaking English at home (OR 1.48, 95% CI 1.15-1.90) higher education (OR 1.67, 95% CI 1.46-1.92) and a prior diagnosis of depression (OR 1.37, 95% CI 1.22-1.55). The multivariate model accounted for limited variance (C-statistic 0.6) in explaining participation. These four factors were not significantly associated with either the primary trial outcome measure or any differential impact by intervention arm. This demonstrates that, among eligible trial participants, few factors were associated with the consent to participate. There was no indication that such self-selection biased the trial results or would limit the generalizability and translation into a public or clinical setting.

Recruitment and Retention for a Weight Loss Maintenance Trial Involving Weight Loss Prior to Randomization

PubMed Central

Grubber, J. M.; McVay, M. A.; Olsen, M. K.; Bolton, J.; Gierisch, J. M.; Taylor, S. S.; Maciejewski, M. L.; Yancy, W. S.

2016-01-01

Abstract Objective A weight loss maintenance trial involving weight loss prior to randomization is challenging to implement due to the potential for dropout and insufficient weight loss. We examined rates and correlates of non‐initiation, dropout, and insufficient weight loss during a weight loss maintenance trial. Methods The MAINTAIN trial involved a 16‐week weight loss program followed by randomization among participants losing at least 4 kg. Psychosocial measures were administered during a screening visit. Weight was obtained at the first group session and 16 weeks later to determine eligibility for randomization. Results Of 573 patients who screened as eligible, 69 failed to initiate the weight loss program. In adjusted analyses, failure to initiate was associated with lower age, lack of a support person, and less encouragement for making dietary changes. Among participants who initiated, 200 dropped out, 82 lost insufficient weight, and 222 lost sufficient weight for randomization. Compared to losing sufficient weight, dropping out was associated with younger age and tobacco use, whereas losing insufficient weight was associated with non‐White race and controlled motivation for physical activity. Conclusions Studies should be conducted to evaluate strategies to maximize recruitment and retention of subgroups that are less likely to initiate and be retained in weight loss maintenance trials. PMID:28090340

Effectiveness versus efficacy trials in COPD: how study design influences outcomes and applicability.

PubMed

Woodcock, Ashley; Boucot, Isabelle; Leather, David A; Crawford, Jodie; Collier, Susan; Bakerly, Nawar Diar; Hilton, Emma; Vestbo, Jørgen

2018-02-01

Guidelines for chronic obstructive pulmonary disease (COPD) management are based largely on results from double-blind randomised controlled trials (RCTs) of efficacy. These trials have high internal validity and test whether a drug is efficacious, but they are conducted in highly selected populations that may differ significantly from patients with COPD seen in routine practice.We compared the baseline characteristics, healthcare use and outcomes between the Salford Lung Study (SLS), an open-label effectiveness RCT, with six recent large-scale efficacy RCTs. We also calculated the proportion of SLS patients who would have been eligible for inclusion in an efficacy RCT by applying the inclusion criteria used in efficacy trials of combination treatments.SLS patients were older, included more females and more current smokers, had more comorbidities (including asthma), and had more often experienced exacerbations prior to inclusion. In the SLS, rates of moderate or severe exacerbations, incidence of overall serious adverse events (SAEs), and SAEs of pneumonia were more frequent. A maximum of 30% of patients enrolled in the SLS would have been eligible for a phase IIIa regulatory exacerbation study.Patients in large COPD efficacy RCTs have limited representativeness compared with an effectiveness trial. This should be considered when interpreting efficacy RCT outcomes and their inclusion into guidelines. Copyright ©ERS 2018.

Use of mindfulness, meditation and relaxation to treat vasomotor symptoms.

PubMed

Goldstein, K M; Shepherd-Banigan, M; Coeytaux, R R; McDuffie, J R; Adam, S; Befus, D; Goode, A P; Kosinski, A S; Masilamani, V; Williams, J W

2017-04-01

Postmenopausal women with bothersome vasomotor symptoms (VMS) often seek alternatives to hormone-based treatment due to medication risks or personal preference. We sought to identify the effects of meditation, mindfulness, hypnosis and relaxation on VMS and health-related quality of life in perimenopausal and postmenopausal women. To do this, we conducted an umbrella review supplemented by new randomized, controlled trials (RCTs) published since the most recent good-quality systematic review for eligible interventions. We searched MEDLINE and the Cochrane Database of Systematic Reviews, PubMed, EMBASE, CINAHL and the Allied and Complementary Medicine Databases. We identified five systematic reviews and six new RCTs that met eligibility criteria. In a new meta-analysis examining four RCTs comparing paced respiration with a control group, we found that paced respiration is not associated with a statistically significant decrease in VMS frequency (standardized mean difference (SMD) 0.04, 95% confidence interval (CI) -0.73 to 0.82, I 2  =   56.6%, three trials) or severity (SMD 0.06, 95% CI -0.69 to 0.80; I 2  =   65.1%, three trials). There was not sufficient new information to conduct meta-analyses that examined the effect of mindfulness or hypnosis on our outcomes of interest. No effect on VMS or quality of life was found between various relaxation or mindfulness interventions.

Successful Reach and Adoption of a workplace health promotion RCT targeting a group of high-risk workers

PubMed Central

2010-01-01

Background Cleaners are rarely introduced to workplace health promotion programs. The study's objective was to evaluate the reach and adoption of a workplace randomized controlled trial (RCT) among cleaners in Denmark. Methods Cleaning businesses with at least 30 employees, that could offer a weekly 1-hour intervention during working hours, were invited to participate. Employees working at least 20 hours/week were invited to answer a screening questionnaire and consent to participate. Analyses determined the differences in health variables between responders and non-responders, consenters and non-consenters, participants and non-participants and between participants of the RCT's three groups: physical coordination training, cognitive-behavioural theory-based training and reference group. Results From 16 eligible workplaces, a representative sample of 50% adopted the trial. Of 758 eligible employees, 78% responded to the screening questionnaire and 49% consented to participate. Consenters and participants differed from non-consenters and non-participants by having higher BMI, more chronic diseases and poorer musculoskeletal health. Conclusions This study indicates that workplace health promotion programs directed at health risk factors among cleaners enable significant adoption and reach to a high-risk subgroup of the Danish workforce. Trial registration Trial registration ISRCTN96241850 PMID:20546592

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

PubMed

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

2010-06-01

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

Impact of Inclusion of Industry Trial Results Registries as an Information Source for Systematic Reviews

PubMed Central

Potthast, Regine; Vervölgyi, Volker; McGauran, Natalie; Kerekes, Michaela F.; Wieseler, Beate; Kaiser, Thomas

2014-01-01

Background Clinical trial results registries may contain relevant unpublished information. Our main aim was to investigate the potential impact of the inclusion of reports from industry results registries on systematic reviews (SRs). Methods We identified a sample of 150 eligible SRs in PubMed via backward selection. Eligible SRs investigated randomized controlled trials of drugs and included at least 2 bibliographic databases (original search date: 11/2009). We checked whether results registries of manufacturers and/or industry associations had also been searched. If not, we searched these registries for additional trials not considered in the SRs, as well as for additional data on trials already considered. We reanalysed the primary outcome and harm outcomes reported in the SRs and determined whether results had changed. A “change” was defined as either a new relevant result or a change in the statistical significance of an existing result. We performed a search update in 8/2013 and identified a sample of 20 eligible SRs to determine whether mandatory results registration from 9/2008 onwards in the public trial and results registry ClinicalTrials.gov had led to its inclusion as a standard information source in SRs, and whether the inclusion rate of industry results registries had changed. Results 133 of the 150 SRs (89%) in the original analysis did not search industry results registries. For 23 (17%) of these SRs we found 25 additional trials and additional data on 31 trials already included in the SRs. This additional information was found for more than twice as many SRs of drugs approved from 2000 as approved beforehand. The inclusion of the additional trials and data yielded changes in existing results or the addition of new results for 6 of the 23 SRs. Of the 20 SRs retrieved in the search update, 8 considered ClinicalTrials.gov or a meta-registry linking to ClinicalTrials.gov, and 1 considered an industry results registry. Conclusion The inclusion of industry and public results registries as an information source in SRs is still insufficient and may result in publication and outcome reporting bias. In addition to an essential search in ClinicalTrials.gov, authors of SRs should consider searching industry results registries. PMID:24743113

Selective attention and response set in the Stroop task.

PubMed

Lamers, Martijn J M; Roelofs, Ardi; Rabeling-Keus, Inge M

2010-10-01

Response set membership contributes much to the interference in the color-word Stroop task. This may be due to selective allocation of attention to eligible responses or, alternatively, to greater inhibition of distractors that are not responses. In the present article, we report two experiments that were designed to adjudicate between these accounts. In Experiment 1, membership was manipulated on a trial-by-trial basis by cuing the possible responses for each trial. Response time (RT) was longer for distractors that corresponded to a cued, eligible response than to an ineligible one. This cuing effect was independent of the number of different responses. In Experiment 2, the distractor was cued on half the trials. Cuing the distractor decreased RTs on both incongruent and congruent trials. Vincentile analyses in both experiments revealed that the effects were constant throughout the entire RT distributions. These results suggest that response set effects arise because of selective allocation of attention to eligible responses.

Gloves, gowns and masks for reducing the transmission of meticillin-resistant Staphylococcus aureus (MRSA) in the hospital setting.

PubMed

López-Alcalde, Jesús; Mateos-Mazón, Marta; Guevara, Marcela; Conterno, Lucieni O; Solà, Ivan; Cabir Nunes, Sheila; Bonfill Cosp, Xavier

2015-07-16

Meticillin-resistant Staphylococcus aureus (MRSA; also known as methicillin-resistant S aureus) is a common hospital-acquired pathogen that increases morbidity, mortality, and healthcare costs. Its control continues to be an unresolved issue in many hospitals worldwide. The evidence base for the effects of the use of gloves, gowns or masks as control measures for MRSA is unclear. To assess the effectiveness of wearing gloves, a gown or a mask when contact is anticipated with a hospitalised patient colonised or infected with MRSA, or with the patient's immediate environment. We searched the Specialised Registers of three Cochrane Groups (Wounds Group on 5 June 2015; Effective Practice and Organisation of Care (EPOC) Group on 9 July 2013; and Infectious Diseases Group on 5 January 2009); CENTRAL (The Cochrane Library 2015, Issue 6); DARE, HTA, NHS EED, and the Methodology Register (The Cochrane Library 2015, Issue 6); MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations (1946 to June week 1 2015); EMBASE (1974 to 4 June 2015); Web of Science (WOS) Core Collection (from inception to 7 June 2015); CINAHL (1982 to 5 June 2015); British Nursing Index (1985 to 6 July 2010); and ProQuest Dissertations & Theses Database (1639 to 11 June 2015). We also searched three trials registers (on 6 June 2015), references list of articles, and conference proceedings. We finally contacted relevant individuals for additional studies. Studies assessing the effects on MRSA transmission of the use of gloves, gowns or masks by any person in the hospital setting when contact is anticipated with a hospitalised patient colonised or infected with MRSA, or with the patient's immediate environment. We did not assess adverse effects or economic issues associated with these interventions.We considered any comparator to be eligible. With regard to study design, only randomised controlled trials (clustered or not) and the following non-randomised experimental studies were eligible: quasi-randomised controlled trials (clustered or not), non-randomised controlled trials (clustered or not), controlled before-and-after studies, controlled cohort before-after studies, interrupted time series studies (controlled or not), and repeated measures studies. We did not exclude any study on the basis of language or date of publication. Two review authors independently decided on eligibility of the studies. Had any study having been included, two review authors would have extracted data (at least for outcome data) and assessed the risk of bias independently. We would have followed the standard methodological procedures suggested by Cochrane and the Cochrane EPOC Group for assessing risk of bias and analysing the data. We identified no eligible studies for this review, either completed or ongoing. We found no studies assessing the effects of wearing gloves, gowns or masks for contact with MRSA hospitalised patients, or with their immediate environment, on the transmission of MRSA to patients, hospital staff, patients' caregivers or visitors. This absence of evidence should not be interpreted as evidence of no effect for these interventions. The effects of gloves, gowns and masks in these circumstances have yet to be determined by rigorous experimental studies, such as cluster-randomised trials involving multiple wards or hospitals, or interrupted time series studies.

Strategies to Support Recruitment of Patients with Life-limiting illness for Research: The Palliative Care Research Cooperative Group

PubMed Central

Hanson, Laura C.; Bull, Janet; Wessell, Kathryn; Massie, Lisa; Bennett, Rachael E.; Kutner, Jean S.; Aziz, Noreen M.; Abernethy, Amy

2014-01-01

Context The Palliative Care Research Cooperative group (PCRC) is the first clinical trials cooperative for palliative care in the United States. Objectives To describe barriers and strategies for recruitment during the inaugural PCRC clinical trial. Methods The parent study was a multi-site randomized controlled trial enrolling adults with life expectancy anticipated to be 1–6 months, randomized to discontinue statins (intervention) vs. to continue on statins (control). To study recruitment best practices, we conducted semi-structured interviews with 18 site Principal Investigators (PI) and Clinical Research Coordinators (CRC), and reviewed recruitment rates. Interviews covered 3 topics – 1) successful strategies for recruitment, 2) barriers to recruitment, and 3) optimal roles of the PI and CRC. Results All eligible site PIs and CRCs completed interviews and provided data on statin protocol recruitment. The parent study completed recruitment of n=381 patients. Site enrollment ranged from 1–109 participants, with an average of 25 enrolled per site. Five major barriers included difficulty locating eligible patients, severity of illness, family and provider protectiveness, seeking patients in multiple settings, and lack of resources for recruitment activities. Five effective recruitment strategies included systematic screening of patient lists, thoughtful messaging to make research relevant, flexible protocols to accommodate patients’ needs, support from clinical champions, and the additional resources of a trials cooperative group. Conclusion The recruitment experience from the multi-site PCRC yields new insights into methods for effective recruitment to palliative care clinical trials. These results will inform training materials for the PCRC and may assist other investigators in the field. PMID:24863152

A phase 2 autologous cellular therapy trial in patients with acute, complete spinal cord injury: pragmatics, recruitment, and demographics.

PubMed

Jones, L A T; Lammertse, D P; Charlifue, S B; Kirshblum, S C; Apple, D F; Ragnarsson, K T; Poonian, D; Betz, R R; Knoller, N; Heary, R F; Choudhri, T F; Jenkins, A L; Falci, S P; Snyder, D A

2010-11-01

Post hoc analysis from a randomized controlled cellular therapy trial in acute, complete spinal cord injury (SCI). Description and quantitative review of study logistics, referral patterns, current practice patterns and subject demographics. Subjects were recruited to one of six international study centers. Data are presented from 1816 patients pre-screened, 75 participants screened and 50 randomized. Of the 1816 patients pre-screened, 53.7% did not meet initial study criteria, primarily due to an injury outside the time window (14 days) or failure to meet neurological criteria (complete SCI between C5 motor/C4 sensory and T11). MRIs were obtained on 339 patients; 51.0% were ineligible based on imaging criteria. Of the 75 participants enrolled, 25 failed screening (SF), leaving 50 randomized. The primary reason for SF was based on the neurological exam (51.9%), followed by failure to meet MRI criteria (22.2%). Of the 50 randomized subjects, there were no significant differences in demographics in the active versus control arms. In those participants for whom data was available, 93.8% (45 of 48) of randomized participants received steroids before study entry, whereas 94.0% (47 of 50) had spine surgery before study enrollment. The 'funnel effect' (large numbers of potentially eligible participants with a small number enrolled) impacts all trials, but was particularly challenging in this trial due to eligibility criteria and logistics. Data collected may provide information on current practice patterns and the issues encountered and addressed may facilitate design of future trials.

Cognitive enhancement treatments for bipolar disorder: A systematic review and methodological recommendations.

PubMed

Miskowiak, Kamilla W; Carvalho, André F; Vieta, Eduard; Kessing, Lars V

2016-10-01

Cognitive dysfunction is an emerging treatment target in bipolar disorder (BD). Several trials have assessed the efficacy of novel pharmacological and psychological treatments on cognition in BD but the findings are contradictory and unclear. A systematic search following the PRISMA guidelines was conducted on PubMed and PsychInfo. Eligible articles reported randomized, controlled or open-label trials investigating pharmacological or psychological treatments targeting cognitive dysfunction in BD. The quality of the identified randomized controlled trials (RCTs) was evaluated with the Cochrane Collaboration's Risk of Bias tool. We identified 19 eligible studies of which 13 were RCTs and six were open-label or non-randomized studies. The findings regarding efficacy on cognition were overall disappointing or preliminary, possibly due to several methodological challenges. For the RCTs, the risk of bias was high in nine cases, unclear in one case and low in three cases. Key reasons for the high risk of bias were lack of details on the randomization process, suboptimal handling of missing data and lack of a priori priority between cognition outcomes. Other challenges were the lack of consensus on whether and how to screen for cognitive impairment and on how to assess efficacy on cognition. In conclusion, methodological problems are likely to impede the success rates of cognition trials in BD. We recommend adherence to the CONSORT guidelines for RCTs, screening for cognitive impairment before inclusion of trial participants and selection of one primary cognition outcome. Future implementation of a 'neurocircuitry-based' biomarker model to evaluate neural target engagement is warranted. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

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

PubMed

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

2009-05-01

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

Desktop software to identify patients eligible for recruitment into a clinical trial: using SARMA to recruit to the ROAD feasibility trial.

PubMed

Treweek, Shaun; Pearson, Ewan; Smith, Natalie; Neville, Ron; Sargeant, Paul; Boswell, Brian; Sullivan, Frank

2010-01-01

Recruitment to trials in primary care is often difficult, particularly when practice staff need to identify study participants with acute conditions during consultations. The Scottish Acute Recruitment Management Application (SARMA) system is linked to general practice electronic medical record (EMR) systems and is designed to provide recruitment support to multi-centre trials by screening patients against trial inclusion criteria and alerting practice staff if the patient appears eligible. For patients willing to learn more about the trial, the software allows practice staff to send the patient's contact details to the research team by text message. To evaluate the ability of the software to support trial recruitment. Software evaluation embedded in a randomised controlled trial. Five general practices in Tayside and Fife, Scotland. SARMA was used to support recruitment to a feasibility trial (the Response to Oral Agents in Diabetes, or ROAD trial) looking at users of oral therapy in diabetes. The technical performance of the software and its utility as a recruitment tool were evaluated. The software was successfully installed at four of the five general practices and recruited 11 of the 29 participants for ROAD (other methods were letter and direct invitation by a practice nurse) and had a recruitment return of 35% (11 of 31 texts sent led to a recruitment). Screen failures were relatively low (7 of 31 referred). Practice staff members were positive about the system. An automated recruitment tool can support primary care trials in Scotland and has the potential to support recruitment in other jurisdictions. It offers a low-cost supplement to other trial recruitment methods and is likely to have a much lower screen failure rate than blanket approaches such as mailshots and newspaper campaigns.

Brazilian oral herbal medication for osteoarthritis: a systematic review protocol.

PubMed

Moura, Mariana Del Grossi; Lopes, Luciane Cruz; Biavatti, Maique Weber; Busse, Jason W; Wang, Li; Kennedy, Sean Alexander; Bhatnaga, Neera; Bergamaschi, Cristiane de Cássia

2016-05-21

Osteoarthritis affects 1 % of the world's population and is the most common cause of musculoskeletal impairment in the elderly. Herbal medications are commonly used in Brazil to manage symptoms associated with osteoarthritis, and some of them are financed by the Brazilian government; however, the effectiveness of most of these agents is uncertain. The aim was to systematically review the efficacy and safety of 13 oral herbal medications used in Brazil for the treatment of osteoarthritis. Randomized clinical trials eligible for our systematic review will enroll adults with osteoarthritis treated by a Brazilian herbal medication or a control group (placebo or active control). Using terms to include all forms of osteoarthritis combined with herbal medications, we will search the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; CINAHL; Web of Science; Health Star; AMED, the database of the Cochrane Complementary Medicine Field, LILACS; CAB abstracts, Clinical trial.gov, WHO trials registry, and Bank of Brazil Thesis (CAPES), to 31 January 2016, without restrictions concerning language or status of publication. Outcomes of interest include the following: symptom relief (e.g., pain), adverse events (gastrointestinal bleeding, epigastric pain, nausea, and allergic reactions), discontinuation due to adverse events, quality of life, and the satisfaction with the treatment. Dichotomous data will be summarized as risk ratios; continuous data will be given as standard average differences with 95 % confidence intervals. A team of reviewers will assess each citation independently for eligibility and in duplicate it. For eligible studies, the same reviewers will perform data extraction, bias risk assessment, and determination of the overall quality of evidence for each of the outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification system. This is the first study that will evaluate the use of herbal medications used in Brazil for the treatment of pain caused by osteoarthritis. The results could guide prescribers in decision-making in clinical practice, to inform the patients with pain caused by osteoarthritis in relation to effective and safe treatment options and to inform the managers of the public health system which of the plants could actually be financed by the Brazilian government. PROSPERO 42015019793.

The effect of nutrition training for health care staff on learner and patient outcomes in adults: a systematic review and meta-analysis.

PubMed

Marples, Owen; Baldwin, Christine; Weekes, C Elizabeth

2017-07-01

Background: Nutrition training for health care staff has been prioritized internationally as a key means of tackling malnutrition; however, there is a lack of clear evidence to support its implementation. Systematic reviews in other fields of training for health care staff indicate that training strategies may have a beneficial impact on learner and patient outcomes. Objectives: We assessed whether nutrition training for health care staff caring for nutritionally vulnerable adults resulted in improved learner and patient outcomes and evaluated the effectiveness of different training strategies. Design: A systematic review of trials of nutrition training for health care staff was conducted. Six databases were searched with key terms relating to malnutrition and nutrition training. Studies were categorized according to cognitive (didactic teaching), behavioral (practical implementation of skills), and psychological (individualized or group feedback and reflection) training strategies. Where sufficient data were available, meta-analysis was performed according to study design and training strategy. All study designs were eligible. The risk of bias was evaluated in accordance with Cochrane guidance. Results: Twenty-four studies met the eligibility criteria: 1 randomized controlled trial, 4 nonrandomized controlled trials, 3 quasi-experimental trials, 13 longitudinal pre-post trials, 2 qualitative studies, and 1 cross-sectional survey. Results from a number of low-quality studies suggest that nutrition training for health care staff may have a beneficial effect on staff nutrition knowledge, practice, and attitude as well as patient nutritional intake. There were insufficient data to determine whether any particular training strategy was more effective than the others. Conclusions: In the absence of high-quality evidence, low-quality studies suggest that nutrition training for health care staff has some positive effects. However, further randomized controlled trials are required to confirm overall efficacy and to explore the impact of training strategies on learner and patient outcomes. © 2017 American Society for Nutrition.

Can Facebook Be Used for Research? Experiences Using Facebook to Recruit Pregnant Women for a Randomized Controlled Trial.

PubMed

Adam, Laura M; Manca, Donna P; Bell, Rhonda C

2016-09-21

Recruitment is often a difficult and costly part of any human research study. Social media and other emerging means of mass communication hold promise as means to complement traditional strategies used for recruiting participants because they can reach a large number of people in a short amount of time. With the ability to target a specified audience, paid Facebook advertisements have potential to reach future research participants of a specific demographic. This paper describes the experiences of a randomized controlled trial in Edmonton, Alberta, attempting to recruit healthy pregnant women between 8 and 20 weeks' gestation for participation in a prenatal study. Various traditional recruitment approaches, in addition to paid Facebook advertisements were trialed. To evaluate the effectiveness of paid advertisements on Facebook as a platform for recruiting pregnant women to a randomized controlled trial in comparison with traditional recruitment approaches. Recruitment using traditional approaches occurred for 7 months, whereas Facebook advertisements ran for a total of 26 days. Interested women were prompted to contact the study staff for a screening call to determine study eligibility. Costs associated with each recruitment approach were recorded and used to calculate the cost to recruit eligible participants. Performance of Facebook advertisements was monitored using Facebook Ads Manager. Of the 115 women included, 39.1% (n=45) of the women who contacted study staff heard about the study through Facebook, whereas 60.9% (n=70) of them heard about it through traditional recruitment approaches. During the 215 days (~7 months) that the traditional approaches were used, the average rate of interest was 0.3 (0.2) women/day, whereas the 26 days of Facebook advertisements resulted in an average rate of interest of 2.8 (1.7) women/day. Facebook advertisements cost Can $506.91 with a cost per eligible participant of Cad $20.28. In comparison, the traditional approaches cost Cad $1087, with approximately Cad $24.15 per eligible participant. Demographic characteristics of women were similar between the 2 recruitment methods except that women recruited using Facebook were significantly earlier in their pregnancy than those recruited using traditional approaches (P<.03). Paid Facebook advertisements hold promise as a platform for reaching pregnant women. The relative ease of placing an advertisement, the comparable cost per participant recruited, and the dramatically improved recruitment rates in comparison with traditional approaches highlight the importance of combining novel and traditional recruitment approaches to recruit women for pregnancy-related studies. ClinicalTrials.gov NCT02711644; https://clinicaltrials.gov/ct2/show/NCT02711644 (Archived by WebCite at http://www.webcitation.org/6kKpagpMk).

Three Studies on Student Outcomes in Higher Education

ERIC Educational Resources Information Center

Cannon, Russell

2016-01-01

This dissertation contains chapters that explore higher education policy issues related to student outcomes. In the first chapter, I examine the results of a controlled randomized trial of a brief, inexpensive phone call outreach to a sample of Pell eligible students at the University of Missouri intended to increase FAFSA filing, on-time FAFSA…

A Review of Treatments for Young Black Males Experiencing Depression

ERIC Educational Resources Information Center

Lindsey, Michael A.; Banks, Andrae; Cota, Catherine F.; Lawrence Scott, Marquisha; Joe, Sean

2018-01-01

The objective was to qualitatively examine the treatment effects of depression interventions on young, Black males (YBM) across treatment providers and settings via a review. Randomized controlled trials (RCTs) seeking to ameliorate depressive symptomology in Black males ages 12-29 were eligible for inclusion. After review of 627 abstracts and 212…

The Prostate Cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy with watchful waiting for men with clinically localized prostate cancer.

PubMed

Wilt, Timothy J

2012-12-01

Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. In the United States, 90% of men with prostate cancer are more than age 60 years, diagnosed by early detection with the prostate-specific antigen (PSA) blood test, and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting (WW), surgery to remove the prostate gland (radical prostatectomy), external-beam radiation therapy and interstitial radiation therapy (brachytherapy), and androgen deprivation. Little is known about the relative effectiveness and harms of treatments because of the paucity of randomized controlled trials. The Department of Veterans Affairs/National Cancer Institute/Agency for Healthcare Research and Quality Cooperative Studies Program Study #407:Prostate Cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy with WW in men with clinically localized prostate cancer. We describe the study rationale, design, recruitment methods, and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy vs WW conducted in Scandinavia. We screened 13 022 men with prostate cancer at 52 US medical centers for potential enrollment. From these, 5023 met initial age, comorbidity, and disease eligibility criteria, and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African American. Approximately 85% reported that they were fully active. The median PSA was 7.8ng/mL (mean 10.2ng/mL). In three-fourths of men, the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk categorizations incorporating PSA levels, Gleason histologic grade, and tumor stage, it was found that approximately 40% had low-risk, 34% had medium-risk, and 21% had high-risk prostate cancer based on local histopathology. Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Scandinavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the United States and quite different from men in the Scandinavian trial. PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States. Results will yield important information regarding the relative effectiveness and harms of surgery compared with WW for men with predominately PSA-detected clinically localized prostate cancer.

The Prostate cancer Intervention Versus Observation Trial:VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy to watchful waiting for men with clinically localized prostate cancer.

PubMed

Wilt, Timothy J; Brawer, Michael K; Barry, Michael J; Jones, Karen M; Kwon, Young; Gingrich, Jeffrey R; Aronson, William J; Nsouli, Imad; Iyer, Padmini; Cartagena, Ruben; Snider, Glenn; Roehrborn, Claus; Fox, Steven

2009-01-01

Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. Ninety percent of men with prostate cancer are over aged 60 years, diagnosed by early detection with the prostate specific antigen (PSA) blood test and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting surgery to remove the prostate gland (radical prostatectomy), external beam radiation therapy and interstitial radiation therapy (brachytherapy) and androgen deprivation. Little is known about the relative effectiveness and harms of treatments due to the paucity of randomized controlled trials. The VA/NCI/AHRQ Cooperative Studies Program Study #407: Prostate cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy to watchful waiting in men with clinically localized prostate cancer. We describe the study rationale, design, recruitment methods and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy versus watchful waiting conducted in Scandinavia. We screened 13,022 men with prostate cancer at 52 United States medical centers for potential enrollment. From these, 5023 met initial age, comorbidity and disease eligibility criteria and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African-American. Approximately 85% reported they were fully active. The median prostate specific antigen (PSA) was 7.8 ng/mL (mean 10.2 ng/mL). In three-fourths of men the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk categorizations incorporating PSA levels, Gleason histologic grade and tumor stage, approximately 43% had low risk, 36% had medium risk and 20% had high-risk prostate cancer. Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Scandinavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the U.S. and quite different from men in the Scandinavian trial. PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States. Results will yield important information regarding the relative effectiveness and harms of surgery compared to watchful waiting for men with predominately PSA detected clinically localized prostate cancer.

Patient-centered recruitment and retention for a randomized controlled study.

PubMed

Chhatre, Sumedha; Jefferson, Ashlie; Cook, Ratna; Meeker, Caitlin R; Kim, Ji Hyun; Hartz, Kayla Marie; Wong, Yu-Ning; Caruso, Adele; Newman, Diane K; Morales, Knashawn H; Jayadevappa, Ravishankar

2018-03-27

Recruitment and retention strategies for patient-centered outcomes research are evolving and research on the subject is limited. In this work, we present a conceptual model of patient-centered recruitment and retention, and describe the recruitment and retention activities and related challenges in a patient-centered comparative effectiveness trial. This is a multicenter, longitudinal randomized controlled trial in localized prostate cancer patients. We recruited 743 participants from three sites over 15 months period (January 2014 to March 2015), and followed them for 24 months. At site 1, of the 773 eligible participants, 551 (72%) were enrolled. At site 2, 34 participants were eligible and 23 (68%) enrolled. Of the 434 eligible participants at site 3, 169 (39%) enrolled. We observed that strategies related to the concepts of trust (e.g., physician involvement, ensuring protection of information), communication (e.g., brochures and pamphlets in physicians' offices, continued contact during regular clinic visits and calling/emailing assessment), attitude (e.g., emphasizing the altruistic value of research, positive attitude of providers and research staff), and expectations (e.g., full disclosure of study requirements and time commitment, update letters) facilitated successful patient recruitment and retention. A stakeholders' advisory board provided important input for the recruitment and retention activities. Active engagement, reminders at the offices, and personalized update letters helped retention during follow-up. Usefulness of telephone recruitment was site specific and, at one site, the time requirement for telephone recruitment was a challenge. We have presented multilevel strategies for successful recruitment and retention in a clinical trial using a patient-centered approach. Our strategies were flexible to accommodate site-level requirements. These strategies as well as the challenges can aid recruitment and retention efforts of future large-scale, patient-centered research studies. Clinicaltrials.gov , ID: NCT02032550 . Registered on 22 November 2013.

Recruitment and Screening for the Testosterone Trials.

PubMed

Cauley, Jane A; Fluharty, Laura; Ellenberg, Susan S; Gill, Thomas M; Ensrud, Kristine E; Barrett-Connor, Elizabeth; Cifelli, Denise; Cunningham, Glenn R; Matsumoto, Alvin M; Bhasin, Shalender; Pahor, Marco; Farrar, John T; Cella, David; Rosen, Raymond C; Resnick, Susan M; Swerdloff, Ronald S; Lewis, Cora E; Molitch, Mark E; Crandall, Jill P; Stephens-Shields, Alisa J; Strorer, Thomas W; Wang, Christina; Anton, Stephen; Basaria, Shehzad; Diem, Susan; Tabatabaie, Vafa; Dougar, Darlene; Hou, Xiaoling; Snyder, Peter J

2015-09-01

We describe the recruitment of men for The Testosterone (T) Trials, which were designed to determine the efficacy of T treatment. Men were eligible if they were ≥65 years, had an average of two morning total T values <275 ng/dL with neither value >300 ng/mL, and had symptoms and objective evidence of mobility limitation, sexual dysfunction, and/or low vitality. Men had to be eligible for and enroll in at least one of these three main trials (physical function, sexual function, vitality). Men were recruited primarily through mass mailings in 12 U.S. communities: 82% of men who contacted the sites did so in response to mailings. Men who responded were screened by telephone to ascertain eligibility. Of 51,085 telephone screens, 53.5% were eligible for further screening. Of 23,889 initial screening visits (SV1), 2,781 (11.6%) men were eligible for the second screening visit (SV2), which 2,261 (81.3%) completed. At SV2, 931 (41.2%) men met the criteria for one or more trials, the T level criterion and had no other exclusions. Of these, 790 (84.6%) were randomized; 99 (12.5%) in all three trials and 348 (44%) in two trials. Their mean age was 72 years and mean body mass index (BMI) was 31.0 kg/m(2). Mean (standard deviation) total T (ng/dL) was 212.0 (40.0). Despite the telephone screening to enrollment ratio of 65 to 1, we met the recruitment goals for each trial. Recruitment of symptomatic older men with low testosterone levels is difficult but feasible. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eligibility for Statin Therapy by the JUPITER Trial Criteria and Subsequent Mortality (From the REGARDS Cohort)

PubMed Central

Cushman, Mary; McClure, Leslie A.; Lakoski, Susan G.; Jenny, Nancy S.

2009-01-01

The Justification of the Use of Statins in Primary Prevention: an Intervention Trial Using Rosuvastatin (JUPITER) reported reduced cardiovascular and all-cause mortality with statin treatment in patients with elevated C-reactive protein (CRP) and average cholesterol, who were not eligible for lipid-lowering treatment based on existing guidelines. We determined the prevalence of eligibility and mortality in a general population sample based on eligibility for statin treatment using JUPITER criteria. We studied 30,229 participants of the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, an observational study of US African-American and white participants aged 45 and older, enrolled in their homes between 2003–2007, and followed biannually by telephone. Among 11,339 participants age-eligible for JUPITER and without a vascular diagnosis or using lipid-lowering treatment, 21% (2,342) met JUPITER entry criteria. Compared to JUPITER participants, they had similar LDL cholesterol and CRP, were more often women, black, had metabolic syndrome and used aspirin for cardioprotection. Over 3.5 years follow-up, the mortality rate among REGARDS participants eligible for JUPITER was 1.17 per 100 person-years (95% CI 0.94–1.42). Compared to those otherwise JUPITER eligible who had CRP <2 mg/L (n=2,620), those with CRP ≥2 mg/L had a multivariable-adjusted relative risk of 1.5 (95% CI, 1.1–2.2) for total mortality. In conclusion, 21% not otherwise eligible would be newly eligible for lipid-lowering treatment based on JUPITER trial eligibility. PMID:20102894

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.

Effects of exercises on Bell's palsy: systematic review of randomized controlled trials.

PubMed

Cardoso, Jefferson Rosa; Teixeira, Elsie Cobra; Moreira, Michelle Damasceno; Fávero, Francis Meire; Fontes, Sissy Veloso; Bulle de Oliveira, Acary Souza

2008-06-01

This study examined the effects of facial exercises associated either with mirror or electromyogram (EMG) biofeedback with respect to complications of delayed recovery in Bell's palsy. Patients with unilateral idiopathic facial palsy were included in this review. Facial exercises associated with mirror and/or EMG biofeedback as treatment. Report of facial symmetry, synkinesis, lip mobility, and physical and social aspects. Four studies of 132 met the eligibility criteria. The studies described mime therapy versus control (n = 50), mirror biofeedback exercise versus control (n = 27), "small" mirror movements versus conventional neuromuscular retraining (n = 10), and EMG biofeedback + mirror training versus mirror training alone. The treatment length varied from 1 to 12 months. Because of the small number of randomized controlled trials, it was not possible to analyze if the exercises, associated either with mirror or EMG biofeedback, were effective. In summary, the available evidence from randomized controlled trials is not yet strong enough to become integrated into clinical practice.

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

PubMed

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

2016-02-24

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

Interpreting survival data from clinical trials of surgery versus stereotactic body radiation therapy in operable Stage I non-small cell lung cancer patients.

PubMed

Samson, Pamela; Keogan, Kathleen; Crabtree, Traves; Colditz, Graham; Broderick, Stephen; Puri, Varun; Meyers, Bryan

2017-01-01

To identify the variability of short- and long-term survival outcomes among closed Phase III randomized controlled trials with small sample sizes comparing SBRT (stereotactic body radiation therapy) and surgical resection in operable clinical Stage I non-small cell lung cancer (NSCLC) patients. Clinical Stage I NSCLC patients who underwent surgery at our institution meeting the inclusion/exclusion criteria for STARS (Randomized Study to Compare CyberKnife to Surgical Resection in Stage I Non-small Cell Lung Cancer), ROSEL (Trial of Either Surgery or Stereotactic Radiotherapy for Early Stage (IA) Lung Cancer), or both were identified. Bootstrapping analysis provided 10,000 iterations to depict 30-day mortality and three-year overall survival (OS) in cohorts of 16 patients (to simulate the STARS surgical arm), 27 patients (to simulate the pooled surgical arms of STARS and ROSEL), and 515 (to simulate the goal accrual for the surgical arm of STARS). From 2000 to 2012, 749/873 (86%) of clinical Stage I NSCLC patients who underwent resection were eligible for STARS only, ROSEL only, or both studies. When patients eligible for STARS only were repeatedly sampled with a cohort size of 16, the 3-year OS rates ranged from 27 to 100%, and 30-day mortality varied from 0 to 25%. When patients eligible for ROSEL or for both STARS and ROSEL underwent bootstrapping with n=27, the 3-year OS ranged from 46 to 100%, while 30-day mortality varied from 0 to 15%. Finally, when patients eligible for STARS were repeatedly sampled in groups of 515, 3-year OS narrowed to 70-85%, with 30-day mortality varying from 0 to 4%. Short- and long-term survival outcomes from trials with small sample sizes are extremely variable and unreliable for extrapolation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Control groups in recent septic shock trials: a systematic review.

PubMed

Pettilä, Ville; Hjortrup, Peter Buhl; Jakob, Stephan M; Wilkman, Erika; Perner, Anders; Takala, Jukka

2016-12-01

The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials. We searched for original articles presenting randomized clinical trials (RCTs) in adult septic shock patients from 2006 to 2016. We included RCTs focusing on septic shock patients with at least two parallel groups and at least 50 patients in the control group. We selected and evaluated data items regarding patients, control group characteristics, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting. A total of 24 RCTs were included (mean n = 287 patients and 71 % of eligible patients were randomized). Of the 24 studies, 14 (58 %) presented baseline data on vasopressors and 58 % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8-32). Of 18 predefined control group characteristics, a mean of 8 (range 2-17) were reported. Only 2 (8 %) trials provided adequate data to confirm that their control group treatment represented usual care. Recent trials in septic shock provide inadequate data on the control group treatment and hemodynamic values. We propose a standardized trial dataset to be created and validated, comprising characteristics of patient population, interventions administered, hemodynamic values achieved, surrogate organ dysfunction, and mortality outcomes, to allow better analysis and interpretation of future trial results.

A Randomized Trial of Genetic and Environmental Risk Assessment (GERA) for Colorectal Cancer Risk in Primary Care: Trial Design and Baseline Findings

PubMed Central

Myers, Ronald E.; Manne, Sharon L.; Wilfond, Benjamin; Sifri, Randa; Ziring, Barry; Wolf, Thomas A.; Cocroft, James; Ueland, Amy; Petrich, Anett; Swan, Heidi; DiCarlo, Melissa; Weinberg, David S.

2010-01-01

Purpose This paper describes an ongoing randomized controlled trial designed to assess the impact of genetic and environmental risk assessment (GERA) on colorectal cancer (CRC) screening. Methods The trial includes asymptomatic patients who are 50-79 years and are not up-to-date with CRC screening guidelines. Patients who responded to a baseline telephone survey are randomized to a GERA or Control group. GERA Group participants meet with a nurse, decide whether to have a GERA blood test (a combination of genetic polymorphism and folate), and, if tested, receive GERA feedback. Follow-up telephone surveys are conducted at one and six months. A chart audit is performed at six months. Results Of 2,223 eligible patients, 562 (25%) have enrolled. Patients who enrolled in the study were significantly younger than those who did not (p<0.001). Participants tended to be 50-59 years (64%), female (58%), white (52%), married (51%), and have more than a high school education (67%). At baseline, most participants had some knowledge of CRC screening and GERA, viewed CRC screening favorably, and reported that they had decided to do screening. Almost half had worries and concerns about CRC. Conclusions One in four eligible primary care patients enrolled in the study. Age was negatively associated with enrollment. Prospective analyses using data for all participants will provide more definitive information on GERA uptake and the impact of GERA feedback. PMID:20828635

A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus.

PubMed

Kluckow, Martin; Jeffery, Michele; Gill, Andy; Evans, Nick

2014-03-01

Failure of closure of the patent ductus arteriosus (PDA) may be associated with harm. Early cardiac ultrasound-targeted treatment of a large PDA may result in a reduction in adverse outcomes and need for later PDA closure with no increase in adverse effects. Multicentre, double-blind, placebo-controlled randomised trial. Three neonatal intensive care units in Australia. Eligible infants born <29 weeks were screened for a large PDA and received indomethacin or placebo before age 12 h. Death or abnormal cranial ultrasound. The trial ceased enrolment early due to lack of availability of indomethacin. 164 eligible infants were screened before 12 h; of the 92 infants with a large PDA, 44 were randomised to indomethacin and 48 to placebo. There was no difference in the main outcome between groups. Infants receiving early indomethacin had significantly less early pulmonary haemorrhage (PH) (2% vs 21%), a trend towards less periventricular/intraventricular haemorrhage (PIVH) (4.5% vs 12.5%) and were less likely to receive later open-label treatment for a PDA (20% vs 40%). The 72 non-randomised infants with a small PDA were at low risk of pulmonary haemorrhage and had an 80% spontaneous PDA closure rate. Early cardiac ultrasound-targeted treatment of a large PDA is feasible and safe, resulted in a reduction in early pulmonary haemorrhage and later medical treatment but had no effect on the primary outcome of death or abnormal cranial ultrasound. Australian New Zealand Clinical Trials Registry (ACTRN12608000295347).

A randomized trial of genetic and environmental risk assessment (GERA) for colorectal cancer risk in primary care: trial design and baseline findings.

PubMed

Myers, Ronald E; Manne, Sharon L; Wilfond, Benjamin; Sifri, Randa; Ziring, Barry; Wolf, Thomas A; Cocroft, James; Ueland, Amy; Petrich, Anett; Swan, Heidi; DiCarlo, Melissa; Weinberg, David S

2011-01-01

This paper describes an ongoing randomized controlled trial designed to assess the impact of genetic and environmental risk assessment (GERA) on colorectal cancer (CRC) screening. The trial includes asymptomatic patients who are 50-79years and are not up-to-date with CRC screening guidelines. Patients who responded to a baseline telephone survey are randomized to a GERA or Control group. GERA group participants meet with a nurse, decide whether to have a GERA blood test (a combination of genetic polymorphism and folate), and, if tested, receive GERA feedback. Follow-up telephone surveys are conducted at 1 and 6months. A chart audit is performed at 6months. Of 2,223 eligible patients, 562 (25%) have enrolled. Patients who enrolled in the study were significantly younger than those who did not (p<0.001). Participants tended to be 50-59years (64%), female (58%), white (52%), married (51%), and have more than a high school education (67%). At baseline, most participants had some knowledge of CRC screening and GERA, viewed CRC screening favorably, and reported that they had decided to do screening. Almost half had worries and concerns about CRC. One in four eligible primary care patients enrolled in the study. Age was negatively associated with enrollment. Prospective analyses using data for all participants will provide more definitive information on GERA uptake and the impact of GERA feedback. Copyright © 2010 Elsevier Inc. All rights reserved.

Randomized Trial of Communication Facilitators to Reduce Family Distress and Intensity of End-of-Life Care.

PubMed

Curtis, J Randall; Treece, Patsy D; Nielsen, Elizabeth L; Gold, Julia; Ciechanowski, Paul S; Shannon, Sarah E; Khandelwal, Nita; Young, Jessica P; Engelberg, Ruth A

2016-01-15

Communication with family of critically ill patients is often poor and associated with family distress. To determine if an intensive care unit (ICU) communication facilitator reduces family distress and intensity of end-of-life care. We conducted a randomized trial at two hospitals. Eligible patients had a predicted mortality greater than or equal to 30% and a surrogate decision maker. Facilitators supported communication between clinicians and families, adapted communication to family needs, and mediated conflict. Outcomes included depression, anxiety, and post-traumatic stress disorder (PTSD) among family 3 and 6 months after ICU and resource use. We identified 488 eligible patients and randomized 168. Of 352 eligible family members, 268 participated (76%). Family follow-up at 3 and 6 months ranged from 42 to 47%. The intervention was associated with decreased depressive symptoms at 6 months (P = 0.017), but there were no significant differences in psychological symptoms at 3 months or anxiety or PTSD at 6 months. The intervention was not associated with ICU mortality (25% control vs. 21% intervention; P = 0.615) but decreased ICU costs among all patients (per patient: $75,850 control, $51,060 intervention; P = 0.042) and particularly among decedents ($98,220 control, $22,690 intervention; P = 0.028). Among decedents, the intervention reduced ICU and hospital length of stay (28.5 vs. 7.7 d and 31.8 vs. 8.0 d, respectively; P < 0.001). Communication facilitators may be associated with decreased family depressive symptoms at 6 months, but we found no significant difference at 3 months or in anxiety or PTSD. The intervention reduced costs and length of stay, especially among decedents. This is the first study to find a reduction in intensity of end-of-life care with similar or improved family distress. Clinical trial registered with www.clinicaltrials.gov (NCT 00720200).

Physical activity interventions in pregnancy and risk of gestational diabetes mellitus: a systematic review and meta-analysis.

PubMed

Russo, Lindsey M; Nobles, Carrie; Ertel, Karen A; Chasan-Taber, Lisa; Whitcomb, Brian W

2015-03-01

Gestational diabetes mellitus (GDM) is a common complication of pregnancy associated with an increased incidence of pregnancy complications, adverse pregnancy outcomes, and maternal and fetal risks of chronic health conditions later in life. Physical activity has been proposed to reduce the risk of GDM and is supported by observational studies, but experimental research assessing its effectiveness is limited and conflicting. We aimed to use meta-analysis to synthesize existing randomized controlled studies of physical activity and GDM. We searched MEDLINE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for eligible studies. The following combination of keywords was used: (pregnant or pregnancy or gestation or gestate or gestational or maternity or maternal or prenatal) AND (exercise or locomotion or activity or training or sports) AND (diabetes or insulin sensitivity or glucose tolerance) AND (random* or trial). Eligibility was restricted to studies that randomized participants to an exercise-only-based intervention (ie, separate from dietary interventions) and presented data regarding GDM risk. Two authors performed the database search, assessment of eligibility, and abstraction of data from included studies, and a third resolved any discrepancies. A total of 469 studies was retrieved, of which 10 met inclusion criteria and could be used for analysis (3,401 participants). Fixed-effects models were used to estimate summary relative risk (RR) and 95% confidence interval (CI) and I to assess heterogeneity. There was a 28% reduced risk (95% CI 9-42%) in the intervention group compared with the control group (RR 0.72, P=.005). Heterogeneity was low (I=12%) and nonsignificant (P=.33). The results from this meta-analysis suggest that physical activity in pregnancy provides a slight protective effect against the development of GDM. Studies evaluating type, timing, duration, and compliance of physical activity regimens are warranted to best inform obstetric guidelines.

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

PubMed

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

2017-11-29

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

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

Delivery of meaningful cancer care: a retrospective cohort study assessing cost and benefit with the ASCO and ESMO frameworks.

PubMed

Del Paggio, Joseph C; Sullivan, Richard; Schrag, Deborah; Hopman, Wilma M; Azariah, Biju; Pramesh, C S; Tannock, Ian F; Booth, Christopher M

2017-07-01

The American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have developed frameworks that quantify survival gains in light of toxicity and quality of life to assess the benefits of cancer therapies. We applied these frameworks to a cohort of contemporary randomised controlled trials to explore agreement between the two approaches and to assess the relation between treatment benefit and cost. We identified all randomised controlled trials of systemic therapies in non-small-cell lung cancer, breast cancer, colorectal cancer, and pancreatic cancer published between Jan 1, 2011, and Dec 31, 2015, and assessed their abstracts and methods. Trials were eligible for inclusion in our cohort if significant differences favouring the experimental group in a prespecified primary or secondary outcome were reported (secondary outcomes were assessed only if primary outcomes were not significant). We assessed trial endpoints with the ASCO and ESMO frameworks at two timepoints 3 months apart to confirm intra-rater reliability. Cohen's κ statistic was calculated to establish agreement between the two frameworks on the basis of the median ASCO score, which was used as an arbitrary threshold of benefit, and the framework-recommended ESMO threshold. Differences in monthly drug cost between the experimental and control groups of each randomised controlled trial (ie, incremental drug cost) were derived from 2016 average wholesale prices. 109 randomised controlled trials were eligible for inclusion, 42 (39%) in non-small-cell lung cancer, 36 (33%) in breast cancer, 25 (23%) in colorectal cancer, and six (6%) in pancreatic cancer. ASCO scores ranged from 2 to 77; median score was 25 (IQR 16-35). 41 (38%) trials met the benefit thresholds in the ESMO framework. Agreement between the two frameworks was fair (κ=0·326). Among the 100 randomised controlled trials for which drug costing data were available, ASCO benefit score and monthly incremental drug costs were negatively correlated (ρ=-0·207; p=0·039). Treatments that met ESMO benefit thresholds had a lower median incremental drug cost than did those that did not meet benefit thresholds (US$2981 [IQR 320-9059] vs $8621 [1174-13 930]; p=0·018). There is only fair correlation between these two major value care frameworks, and negative correlations between framework outputs and drug costs. Delivery of optimal cancer care in a sustainable health system will necessitate future oncologists, investigators, and policy makers to reconcile the disconnect between drug cost and clinical benefit. None. Copyright © 2017 Elsevier Ltd. All rights reserved.

Individualized Statin Benefit for Determining Statin Eligibility in the Primary Prevention of Cardiovascular Disease.

PubMed

Thanassoulis, George; Williams, Ken; Altobelli, Kathleen Kimler; Pencina, Michael J; Cannon, Christopher P; Sniderman, Allan D

2016-04-19

Current guidelines recommend statins in the primary prevention of cardiovascular disease on the basis of predicted cardiovascular risk without directly considering the expected benefits of statin therapy based on the available randomized, controlled trial evidence. We included 2134 participants representing 71.8 million American residents potentially eligible for statins in primary prevention from the National Health and Nutrition Examination Survey for the years 2005 to 2010. We compared statin eligibilities using 2 separate approaches: a 10-year risk-based approach (≥7.5% 10-year risk) and an individualized benefit approach (ie, based on predicted absolute risk reduction over 10 years [ARR10] ≥2.3% from randomized, controlled trial data). A risk-based approach led to the eligibility of 15.0 million (95% confidence interval, 12.7-17.3 million) Americans, whereas a benefit-based approach identified 24.6 million (95% confidence interval, 21.0-28.1 million). The corresponding numbers needed to treat over 10 years were 21 (range, 9-44) and 25 (range, 9-44). The benefit-based approach identified 9.5 million lower-risk (<7.5% 10-year risk) Americans not currently eligible for statin treatment who had the same or greater expected benefit from statins (≥2.3% ARR10) compared with higher-risk individuals. This lower-risk/acceptable-benefit group includes younger individuals (mean age, 55.2 versus 62.5 years; P<0.001 for benefit based versus risk based) with higher low-density lipoprotein cholesterol (140 versus133 mg/dL; P=0.01). Statin treatment in this group would be expected to prevent an additional 266 508 cardiovascular events over 10 years. An individualized statin benefit approach can identify lower-risk individuals who have equal or greater expected benefit from statins in primary prevention compared with higher-risk individuals. This approach may help develop guideline recommendations that better identify individuals who meaningfully benefit from statin therapy. © 2016 American Heart Association, Inc.

Recruiting pregnant smokers from Text4baby for a randomized controlled trial of Quit4baby.

PubMed

Leavitt, Leah; Abroms, Lorien; Johnson, Pamela; Schindler-Ruwisch, Jennifer; Bushar, Jessica; Singh, Indira; Cleary, Sean D; McInvale, Whitney; Turner, Monique

2017-06-01

Recruiting pregnant smokers into clinical trials is challenging since this population tends to be disadvantaged, the behavior is stigmatized, and the intervention window is limited. The purpose of this study is to test the feasibility and effectiveness of recruiting pregnant smokers into a smoking cessation trial by sending recruitment text messages to an existing subscriber list. Recruitment messages were sent to subscribers flagged as pregnant in Text4baby, a national text messaging program for pregnant women and mothers. Four recruitment messages were rotated to test the effectiveness of different emotional frames and a financial incentive. Study staff called subscribers who expressed interest to screen for eligibility and enroll eligible women. Between October 6, 2015 and February 2, 2016, 10,194 recruitment messages were sent to Text4baby subscribers flagged as pregnant, and 10.18% (1038) responded indicating interest. No significant increase in cancellation was observed compared to subscribers who received other ad hoc messages. Of respondents, 54.05% (561) were reached by phone for follow-up, and 21.97% (228) were found to be eligible. Among the eligible, 87% (199) pregnant smokers enrolled. The recruitment message with a pride emotional appeal had a significantly higher response (p = 0.02) compared to the recruitment message with no emotional appeal, but enrollment did not significantly differ between recruitment messages with different emotional appeals. The recruitment messages with a reference to financial incentive yielded higher response (p < 0.01) and enrollment (p = 0.03) compared to a recruitment message without. This study demonstrates success recruiting pregnant smokers using text message. Future studies should consider building on this approach for recruiting high-risk populations.

Can jurors recognize missing control groups, confounds, and experimenter bias in psychological science?

PubMed

McAuliff, Bradley D; Kovera, Margaret Bull; Nunez, Gabriel

2009-06-01

This study examined the ability of jury-eligible community members (N = 248) to detect internal validity threats in psychological science presented during a trial. Participants read a case summary in which an expert testified about a study that varied in internal validity (valid, missing control group, confound, and experimenter bias) and ecological validity (high, low). Ratings of expert evidence quality and expert credibility were higher for the valid versus missing control group versions only. Internal validity did not influence verdict or ratings of plaintiff credibility and no differences emerged as a function of ecological validity. Expert evidence quality, expert credibility, and plaintiff credibility were positively correlated with verdict. Implications for the scientific reasoning literature and for trials containing psychological science are discussed.

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.

Implementing guidelines in nursing homes: a systematic review.

PubMed

Diehl, Heinz; Graverholt, Birgitte; Espehaug, Birgitte; Lund, Hans

2016-07-25

Research on guideline implementation strategies has mostly been conducted in settings which differ significantly from a nursing home setting and its transferability to the nursing home setting is therefore limited. The objective of this study was to systematically review the effects of interventions to improve the implementation of guidelines in nursing homes. A systematic literature search was conducted in the Cochrane Library, CINAHL, Embase, MEDLINE, DARE, HTA, CENTRAL, SveMed + and ISI Web of Science from their inception until August 2015. Reference screening and a citation search were performed. Studies were eligible if they evaluated any type of guideline implementation strategy in a nursing home setting. Eligible study designs were systematic reviews, randomised controlled trials, non-randomised controlled trials, controlled before-after studies and interrupted-time-series studies. The EPOC risk of bias tool was used to evaluate the risk of bias in the included studies. The overall quality of the evidence was rated using GRADE. Five cluster-randomised controlled trials met the inclusion criteria, evaluating a total of six different multifaceted implementation strategies. One study reported a small statistically significant effect on professional practice, and two studies demonstrated small to moderate statistically significant effects on patient outcome. The overall quality of the evidence for all comparisons was low or very low using GRADE. Little is known about how to improve the implementation of guidelines in nursing homes, and the evidence to support or discourage particular interventions is inconclusive. More implementation research is needed to ensure high quality of care in nursing homes. PROSPERO 2014: CRD42014007664.

A review of reporting of participant recruitment and retention in RCTs in six major journals

PubMed Central

Toerien, Merran; Brookes, Sara T; Metcalfe, Chris; de Salis, Isabel; Tomlin, Zelda; Peters, Tim J; Sterne, Jonathan; Donovan, Jenny L

2009-01-01

Background Poor recruitment and retention of participants in randomised controlled trials (RCTs) is problematic but common. Clear and detailed reporting of participant flow is essential to assess the generalisability and comparability of RCTs. Despite improved reporting since the implementation of the CONSORT statement, important problems remain. This paper aims: (i) to update and extend previous reviews evaluating reporting of participant recruitment and retention in RCTs; (ii) to quantify the level of participation throughout RCTs. Methods We reviewed all reports of RCTs of health care interventions and/or processes with individual randomisation, published July–December 2004 in six major journals. Short, secondary or interim reports, and Phase I/II trials were excluded. Data recorded were: general RCT details; inclusion of flow diagram; participant flow throughout trial; reasons for non-participation/withdrawal; target sample sizes. Results 133 reports were reviewed. Overall, 79% included a flow diagram, but over a third were incomplete. The majority reported the flow of participants at each stage of the trial after randomisation. However, 40% failed to report the numbers assessed for eligibility. Percentages of participants retained at each stage were high: for example, 90% of eligible individuals were randomised, and 93% of those randomised were outcome assessed. On average, trials met their sample size targets. However, there were some substantial shortfalls: for example 21% of trials reporting a sample size calculation failed to achieve adequate numbers at randomisation, and 48% at outcome assessment. Reporting of losses to follow up was variable and difficult to interpret. Conclusion The majority of RCTs reported the flow of participants well after randomisation, although only two-thirds included a complete flow chart and there was great variability over the definition of "lost to follow up". Reporting of participant eligibility was poor, making assessments of recruitment practice and external validity difficult. Reporting of participant flow throughout RCTs could be improved by small changes to the CONSORT chart. PMID:19591685

A review of reporting of participant recruitment and retention in RCTs in six major journals.

PubMed

Toerien, Merran; Brookes, Sara T; Metcalfe, Chris; de Salis, Isabel; Tomlin, Zelda; Peters, Tim J; Sterne, Jonathan; Donovan, Jenny L

2009-07-10

Poor recruitment and retention of participants in randomised controlled trials (RCTs) is problematic but common. Clear and detailed reporting of participant flow is essential to assess the generalisability and comparability of RCTs. Despite improved reporting since the implementation of the CONSORT statement, important problems remain. This paper aims: (i) to update and extend previous reviews evaluating reporting of participant recruitment and retention in RCTs; (ii) to quantify the level of participation throughout RCTs. We reviewed all reports of RCTs of health care interventions and/or processes with individual randomisation, published July-December 2004 in six major journals. Short, secondary or interim reports, and Phase I/II trials were excluded. Data recorded were: general RCT details; inclusion of flow diagram; participant flow throughout trial; reasons for non-participation/withdrawal; target sample sizes. 133 reports were reviewed. Overall, 79% included a flow diagram, but over a third were incomplete. The majority reported the flow of participants at each stage of the trial after randomisation. However, 40% failed to report the numbers assessed for eligibility. Percentages of participants retained at each stage were high: for example, 90% of eligible individuals were randomised, and 93% of those randomised were outcome assessed. On average, trials met their sample size targets. However, there were some substantial shortfalls: for example 21% of trials reporting a sample size calculation failed to achieve adequate numbers at randomisation, and 48% at outcome assessment. Reporting of losses to follow up was variable and difficult to interpret. The majority of RCTs reported the flow of participants well after randomisation, although only two-thirds included a complete flow chart and there was great variability over the definition of "lost to follow up". Reporting of participant eligibility was poor, making assessments of recruitment practice and external validity difficult. Reporting of participant flow throughout RCTs could be improved by small changes to the CONSORT chart.

Moxibustion for pain relief in patients with primary dysmenorrhea: A randomized controlled trial

PubMed Central

Bo, Linna; Lao, Lixing; Chen, Jiao; Yu, Siyi; Yu, Zheng; Tang, Hongzhi; Yi, Ling; Wu, Xi; Yang, Jie; Liang, Fanrong

2017-01-01

Background Though moxibustion is frequently used to treat primary dysmenorrhea in China, relevant evidence supporting its effectiveness is still scanty. Methods This study was a pragmatic randomized, conventional drug controlled, open-labeled clinical trial. After initial screen, 152 eligible participants were averagely randomized to receive two different treatment strategies: Moxibustion and conventional drugs. Participants and practitioners were not blinded in this study. The duration of each treatment was 3 months. The primary outcome was pain relief measured by the Visual Analogue Scale. The menstrual pain severity was recorded in a menstrual pain diary. Results 152 eligible patients were included but only 133 of them eventually completed the whole treatment course. The results showed that the menstrual pain intensity in experimental group and control group was reduced from 6.38±1.28 and 6.41±1.29, respectively, at baseline, to 2.54±1.41 and 2.47±1.29 after treatment. The pain reduction was not significantly different between these two groups (P = 0.76), however; the pain intensity was significantly reduced relative to baseline for each group (P<0.01). Three months after treatment, the effectiveness of moxibustion sustained and started to be superior to the drug’s effect (-0.87, 95%CI -1.32 to -0.42, P<0.01). Secondary outcome analyses showed that moxibustion was as effective as drugs in alleviating menstrual pain-related symptoms. The serum levels of pain mediators, such as PGF2α, OT, vWF, β-EP, PGE2, were significantly improved after treatment in both groups (P<0.05). No adverse events were reported in this trial. Conclusions Both moxibustion and conventional drug showed desirable merits in managing menstrual pain, given their treatment effects and economic costs. This study as a pragmatic trial only demonstrates the effectiveness, not the efficacy, of moxibustion for menstrual pain. It can’t rule out the effect of psychological factors during treatment process, because no blind procedure or sham control was used due to availability. In clinical practice, moxibustion should be used at the discretion of patients and their physicians. Trial registration ClinialTrials.gov NCT01972906 PMID:28170396

Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials

PubMed Central

Tzoulaki, Ioanna; Zgaga, Lina; Ioannidis, John P A

2014-01-01

Objective To evaluate the breadth, validity, and presence of biases of the associations of vitamin D with diverse outcomes. Design Umbrella review of the evidence across systematic reviews and meta-analyses of observational studies of plasma 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D concentrations and randomised controlled trials of vitamin D supplementation. Data sources Medline, Embase, and screening of citations and references. Eligibility criteria Three types of studies were eligible for the umbrella review: systematic reviews and meta-analyses that examined observational associations between circulating vitamin D concentrations and any clinical outcome; and meta-analyses of randomised controlled trials assessing supplementation with vitamin D or active compounds (both established and newer compounds of vitamin D). Results 107 systematic literature reviews and 74 meta-analyses of observational studies of plasma vitamin D concentrations and 87 meta-analyses of randomised controlled trials of vitamin D supplementation were identified. The relation between vitamin D and 137 outcomes has been explored, covering a wide range of skeletal, malignant, cardiovascular, autoimmune, infectious, metabolic, and other diseases. Ten outcomes were examined by both meta-analyses of observational studies and meta-analyses of randomised controlled trials, but the direction of the effect and level of statistical significance was concordant only for birth weight (maternal vitamin D status or supplementation). On the basis of the available evidence, an association between vitamin D concentrations and birth weight, dental caries in children, maternal vitamin D concentrations at term, and parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis is probable, but further studies and better designed trials are needed to draw firmer conclusions. In contrast to previous reports, evidence does not support the argument that vitamin D only supplementation increases bone mineral density or reduces the risk of fractures or falls in older people. Conclusions Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable. PMID:24690624

Effects of community health interventions on under-5 mortality in rural Guinea-Bissau (EPICS): a cluster-randomised controlled trial.

PubMed

Boone, Peter; Elbourne, Diana; Fazzio, Ila; Fernandes, Samory; Frost, Chris; Jayanty, Chitra; King, Rebecca; Mann, Vera; Piaggio, Gilda; dos Santos, Albino; Walker, Polly R

2016-05-01

Evidence suggests that community-based interventions that promote improved home-based practices and care-seeking behaviour can have a large impact on maternal and child mortality in regions where rates are high. We aimed to assess whether an intervention package based on the WHO Integrated Management of Childhood Illness handbook and community mobilisation could reduce under-5 mortality in rural Guinea-Bissau, where the health service infrastructure is weak. We did a non-masked cluster-randomised controlled trial (EPICS) in the districts of Tombali and Quinara in Guinea-Bissau. Clusters of rural villages were stratified by ethnicity and distance from a regional health centre, and randomly assigned (1:1) to intervention or control using a computerised random number generator. Women were eligible if they lived in one of the clusters at baseline survey prior to randomisation and if they were aged 15-49 years or were primary caregivers of children younger than 5 years. Their children were eligible if they were younger than 5 years or were liveborn after intervention services could be implemented on July 1, 2008. In villages receiving the intervention, community health clubs were established, community health workers were trained in case management, and traditional birth attendants were trained to care for pregnant women and newborn babies, and promote facility-based delivery. Registered nurses supervised community health workers and offered mobile clinic services. Health centres were not improved. The control group received usual services. The primary outcome was the proportion of children dying under age 5 years, and was analysed in all eligible children up to final visits to villages between Jan 1 and March 31, 2011. This trial is registered with ISRCTN, number ISRCTN52433336. On Aug 30, 2007, we randomly assigned 146 clusters to intervention (73 clusters, 5669 women, and 4573 children) or control (73 clusters, 5840 women, and 4675 children). From randomisation until the end of the trial (last visit by June 30, 2011), the intervention clusters had 3093 livebirths and the control clusters had 3194. 6729 children in the intervention group and 6894 in the control group aged 0-5 years on July 1, 2008, or liveborn subsequently were analysed for mortality outcomes. 311 (4·6%) of 6729 children younger than 5 years died in the intervention group compared with 273 (4·0%) of 6894 in the control group (relative risk 1·16 [95% CI 0·99-1·37]). Our package of community-based interventions did not reduce under-5 mortality in rural Guinea-Bissau. The short timeframe and other trial limitations might have affected our results. Community-based health promotion and basic first-line services in fragile contexts with weak secondary health service infrastructure might be insufficient to reduce child deaths. Effective Intervention. Copyright © 2016 Boone et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd.. All rights reserved.

Effect of edaravone on radiation-induced brain necrosis in patients with nasopharyngeal carcinoma after radiotherapy: a randomized controlled trial.

PubMed

Tang, Yamei; Rong, Xiaoming; Hu, Weihan; Li, Guoqian; Yang, Xiaoxia; Yang, Jianhua; Xu, Pengfei; Luo, Jinjun

2014-11-01

Excessive generation of free radicals plays a critical role in the pathogenesis of radiation-induced brain injury. This study was designed to evaluate the protective effect of edaravone, a free radical scavenger, on radiation-induced brain necrosis in patients with nasopharyngeal carcinoma. Eligible patients were randomized 1:1 to the control group and the edaravone group (intravenous 30 mg twice per day for 2 weeks). Both groups received intravenous conventional steroid therapy and were monitored by brain MRI and LENT/SOMA scales prior to the entry of the trial and at 3-months after completing the trial. The primary end point was a 3-month response rate of the proportional changes determined by MRI. The trial is registered at Clinicaltrials.gov Identifier: NCT01865201. Between 2009 and 2012, we enrolled 154 patients. Of whom 137 were eligible for analysis. The volumes of necrosis estimated on T(2)-weighted image showed that 55.6 % edaravone-treated patients (40 out of 72) showed edema decreases ≥25 %, which was significantly higher than that in the control group (35.4 %, 23 out of 65, p = 0.025). Forty-four patients treated with edaravone (61.1 %) reported improvement in neurologic symptoms and signs evaluated by LENT/SOMA scales, while the rate was 38.5 % in the control group (p = 0.006). MRI of the edaravone group showed a significant decrease in area of T(1)-weighted contrast enhancement (1.67 ± 4.69 cm(2), p = 0.004) and the T(2)-weighted edema (5.08 ± 10.32 cm(2), p = 0.000). Moreover, compared with those in control group, patients with edaravone exhibited significantly better radiological improvement measured by T(2)-weighted image (p = 0.042). Administration of edaravone, in adjunct to steroid regimen, might provide a better outcome in patients with radiation-induced brain necrosis.

An educational intervention to reduce pain and improve pain management for Malawian people living with HIV/AIDS and their family carers: study protocol for a randomised controlled trial.

PubMed

Nkhoma, Kennedy; Seymour, Jane; Arthur, Antony

2013-07-13

Many HIV/AIDS patients experience pain often due to advanced HIV/AIDS infection and side effects of treatment. In sub-Saharan Africa, pain management for people with HIV/AIDS is suboptimal. With survival extended as a direct consequence of improved access to antiretroviral therapy, the prevalence of HIV/AIDS related pain is increasing. As most care is provided at home, the management of pain requires patient and family involvement. Pain education is an important aspect in the management of pain in HIV/AIDS patients. Studies of the effectiveness of pain education interventions for people with HIV/AIDS have been conducted almost exclusively in western countries. A randomised controlled trial is being conducted at the HIV and palliative care clinics of two public hospitals in Malawi. To be eligible, patient participants must have a diagnosis of HIV/AIDS (stage III or IV). Carer participants must be the individual most involved in the patient's unpaid care. Eligible participants are randomised to either: (1) a 30-minute face-to-face educational intervention covering pain assessment and management, augmented by a leaflet and follow-up telephone call at two weeks; or (2) usual care. Those allocated to the usual care group receive the educational intervention after follow-up assessments have been conducted (wait-list control group). The primary outcome is pain severity measured by the Brief Pain Inventory. Secondary outcomes are pain interference, patient knowledge of pain management, patient quality of life, carer knowledge of pain management, caregiver motivation and carer quality of life. Follow-up assessments are conducted eight weeks after randomisation by palliative care nurses blind to allocation. This randomised controlled trial conducted in sub-Saharan Africa among people living with HIV/AIDS and their carers will assess whether a pain education intervention is effective in reducing pain and improving pain management, quality of life and carer motivation. Current Controlled Trials ISRCTN72861423.

Effect of preventive primary care outreach on health related quality of life among older adults at risk of functional decline: randomised controlled trial

PubMed Central

Brazil, Kevin; Hutchison, Brian; Kaczorowski, Janusz; Dalby, Dawn M; Goldsmith, Charles H; Furlong, William

2010-01-01

Objective To evaluate the impact of a provider initiated primary care outreach intervention compared with usual care among older adults at risk of functional decline. Design Randomised controlled trial. Setting Patients enrolled with 35 family physicians in five primary care networks in Hamilton, Ontario, Canada. Participants Patients were eligible if they were 75 years of age or older and were not receiving home care services. Of 3166 potentially eligible patients, 2662 (84%) completed the validated postal questionnaire used to determine risk of functional decline. Of 1724 patients who met the risk criteria, 769 (45%) agreed to participate and 719 were randomised. Intervention The 12 month intervention, provided by experienced home care nurses in 2004-6, consisted of a comprehensive initial assessment using the resident assessment instrument for home care; collaborative care planning with patients, their families, and family physicians; health promotion; and referral to community health and social support services. Main outcome measures Quality adjusted life years (QALYs), use and costs of health and social services, functional status, self rated health, and mortality. Results The mean difference in QALYs between intervention and control patients during the study period was not statistically significant (0.017, 95% confidence interval −0.022 to 0.056; P=0.388). The mean difference in overall cost of prescription drugs and services between the intervention and control groups was not statistically significant, (−$C165 (£107; €118; $162), 95% confidence interval −$C16 545 to $C16 214; P=0.984). Changes over 12 months in functional status and self rated health were not significantly different between the intervention and control groups. Ten patients died in each group. Conclusions The results of this study do not support adoption of this preventive primary care intervention for this target population of high risk older adults. Trial registration Clinical trials NCT00134836. PMID:20400483

Eligibility for statin therapy by the JUPITER trial criteria and subsequent mortality.

PubMed

Cushman, Mary; McClure, Leslie A; Lakoski, Susan G; Jenny, Nancy S

2010-01-01

Justification for the Use of Statins in Primary Prevention: An Intervention Trial Using Rosuvastatin (JUPITER) reported reduced cardiovascular and all-cause mortality with statin treatment in patients with elevated C-reactive protein (CRP) and average cholesterol levels who were not eligible for lipid-lowering treatment on the basis of existing guidelines. The aim of this study was to determine the prevalence of eligibility and mortality in a general population sample on the basis of eligibility for statin treatment using the JUPITER criteria. The study group consisted of 30,229 participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, an observational study of US African American and white participants aged > or =45 years, enrolled in their homes from 2003 to 2007 and followed biannually by telephone. Among 11,339 participants age eligible for JUPITER and without vascular diagnoses or using lipid-lowering treatment, 21% (n = 2,342) met JUPITER entry criteria. Compared with JUPITER participants, they had similar low-density lipoprotein cholesterol and CRP levels, were more often women, were more often black, had metabolic syndrome, and used aspirin for cardioprotection. Over 3.5 years of follow-up, the mortality rate in REGARDS participants eligible for JUPITER was 1.17 per 100 patient-years (95% confidence interval 0.94 to 1.42). Compared with those otherwise JUPITER eligible who had CRP levels <2 mg/L (n = 2,620), those with CRP levels > or =2 mg/L had a multivariate-adjusted relative risk of 1.5 (95% confidence interval 1.1 to 2.2) for total mortality. In conclusion, 21% not otherwise eligible would be newly eligible for lipid lowering treatment on the basis of JUPITER trial eligibility.

Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies.

PubMed

Li, Ling; Li, Sheyu; Deng, Ke; Liu, Jiali; Vandvik, Per Olav; Zhao, Pujing; Zhang, Longhao; Shen, Jiantong; Bala, Malgorzata M; Sohani, Zahra N; Wong, Evelyn; Busse, Jason W; Ebrahim, Shanil; Malaga, German; Rios, Lorena P; Wang, Yingqiang; Chen, Qunfei; Guyatt, Gordon H; Sun, Xin

2016-02-17

To examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of heart failure or hospital admission for heart failure in patients with type 2 diabetes. Systematic review and meta-analysis of randomised and observational studies. Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov searched up to 25 June 2015, and communication with experts. Randomised controlled trials, non-randomised controlled trials, cohort studies, and case-control studies that compared DPP-4 inhibitors against placebo, lifestyle modification, or active antidiabetic drugs in adults with type 2 diabetes, and explicitly reported the outcome of heart failure or hospital admission for heart failure. Teams of paired reviewers independently screened for eligible studies, assessed risk of bias, and extracted data using standardised, pilot tested forms. Data from trials and observational studies were pooled separately; quality of evidence was assessed by the GRADE approach. Eligible studies included 43 trials (n=68,775) and 12 observational studies (nine cohort studies, three nested case-control studies; n=1,777,358). Pooling of 38 trials reporting heart failure provided low quality evidence for a possible similar risk of heart failure between DPP-4 inhibitor use versus control (42/15,701 v 33/12,591; odds ratio 0.97 (95% confidence interval 0.61 to 1.56); risk difference 2 fewer (19 fewer to 28 more) events per 1000 patients with type 2 diabetes over five years). The observational studies provided effect estimates generally consistent with trial findings, but with very low quality evidence. Pooling of the five trials reporting admission for heart failure provided moderate quality evidence for an increased risk in patients treated with DPP-4 inhibitors versus control (622/18,554 v 552/18,474; 1.13 (1.00 to 1.26); 8 more (0 more to 16 more)). The pooling of adjusted estimates from observational studies similarly suggested (with very low quality evidence) a possible increased risk of admission for heart failure (adjusted odds ratio 1.41, 95% confidence interval 0.95 to 2.09) in patients treated with DPP-4 inhibitors (exclusively sitagliptin) versus no use. The relative effect of DPP-4 inhibitors on the risk of heart failure in patients with type 2 diabetes is uncertain, given the relatively short follow-up and low quality of evidence. Both randomised controlled trials and observational studies, however, suggest that these drugs may increase the risk of hospital admission for heart failure in those patients with existing cardiovascular diseases or multiple risk factors for vascular diseases, compared with no use. 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.

Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies.

PubMed

Li, Xue; Meng, Xiangrui; Timofeeva, Maria; Tzoulaki, Ioanna; Tsilidis, Konstantinos K; Ioannidis, John PA; Campbell, Harry; Theodoratou, Evropi

2017-06-07

Objective  To map the diverse health outcomes associated with serum uric acid (SUA) levels. Design  Umbrella review. Data sources  Medline, Embase, Cochrane Database of Systematic Reviews, and screening of citations and references. Eligibility criteria  Systematic reviews and meta-analyses of observational studies that examined associations between SUA level and health outcomes, meta-analyses of randomised controlled trials that investigated health outcomes related to SUA lowering treatment, and Mendelian randomisation studies that explored the causal associations of SUA level with health outcomes. Results  57 articles reporting 15 systematic reviews and144 meta-analyses of observational studies (76 unique outcomes), 8 articles reporting 31 meta-analyses of randomised controlled trials (20 unique outcomes), and 36 articles reporting 107 Mendelian randomisation studies (56 unique outcomes) met the eligibility criteria. Across all three study types, 136 unique health outcomes were reported. 16 unique outcomes in meta-analyses of observational studies had P<10 -6 , 8 unique outcomes in meta-analyses of randomised controlled trials had P<0.001, and 4 unique outcomes in Mendelian randomisation studies had P<0.01. Large between study heterogeneity was common (80% and 45% in meta-analyses of observational studies and of randomised controlled trials, respectively). 42 (55%) meta-analyses of observational studies and 7 (35%) meta-analyses of randomised controlled trials showed evidence of small study effects or excess significance bias. No associations from meta-analyses of observational studies were classified as convincing; five associations were classified as highly suggestive (increased risk of heart failure, hypertension, impaired fasting glucose or diabetes, chronic kidney disease, coronary heart disease mortality with high SUA levels). Only one outcome from randomised controlled trials (decreased risk of nephrolithiasis recurrence with SUA lowering treatment) had P<0.001, a 95% prediction interval excluding the null, and no large heterogeneity or bias. Only one outcome from Mendelian randomisation studies (increased risk of gout with high SUA levels) presented convincing evidence. Hypertension and chronic kidney disease showed concordant evidence in meta-analyses of observational studies, and in some (but not all) meta-analyses of randomised controlled trials with respective intermediate or surrogate outcomes, but they were not statistically significant in Mendelian randomisation studies. Conclusion  Despite a few hundred systematic reviews, meta-analyses, and Mendelian randomisation studies exploring 136 unique health outcomes, convincing evidence of a clear role of SUA level only exists for gout and nephrolithiasis. 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.

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

PubMed

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

2013-10-01

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

Characterization of patients with diabetic foot disease presenting to an Irish Podiatry Centre: profiling suitability for entry to a clinical trial of advanced wound therapeutics.

PubMed

Mahon, A M; MacGilchrist, C; McIntosh, C; O'Brien, T

2017-08-01

Diabetes mellitus, coined the 'Black Death of the Twenty-First Century', is associated with complications, including foot ulceration with potential loss of limb. There is a need for development of new wound therapies through completion of robust clinical trials. To profile demographics and wound characteristics of an Irish cohort with diabetes, forecast eligibility for entry to a clinical trial of advanced wound therapeutics, and adjust criteria to optimize eligibility for enrolment. A cross-sectional study of out-patients attending a Podiatry centre over 12 weeks was conducted. Information was collected through clinical assessment, including Neuropathy Disability Score and Ankle-Brachial Pressure Index. Ulcers were characterised as 'healing' or 'non-healing'; a 'healing' wound decreased by 30 % over the previous month, accomplished by retrospective analysis of files. Statistics, including binomial logistic regression and column analysis for eligibility assessment, were conducted. Seventy-four participants were identified with a mean age of 67 (± 8.79) years. Non-healing DFU status correlated significantly with larger wound area (P = 0.013), infection (P = 0.009), and greater degrees of ischaemia (P = 0.015). The eligibility criteria were modelled after those proposed by the EU consortium project REDDSTAR. In this Irish population, these criteria limit eligibility to 1.4 %. This research found an eligibility criterion of wound area 2-10 cm 2 for enrolment in a clinical trial of mesenchymal stromal cell therapy too restrictive. Extension of wound area to 1-10 cm 2 and the inclusion of neuro-ischaemic ulcers increased eligibility for enrolment from 1.4 to 20 %.

Cartilage Restoration of the Knee: A Systematic Review and Meta-analysis of Level 1 Studies.

PubMed

Mundi, Raman; Bedi, Asheesh; Chow, Linda; Crouch, Sarah; Simunovic, Nicole; Sibilsky Enselman, Elizabeth; Ayeni, Olufemi R

2016-07-01

Focal cartilage defects of the knee are a substantial cause of pain and disability in active patients. There has been an emergence of randomized controlled trials evaluating surgical techniques to manage such injuries, including marrow stimulation (MS), autologous chondrocyte implantation (ACI), and osteochondral autograft transfer (OAT). A meta-analysis was conducted to determine if any single technique provides superior clinical results at intermediate follow-up. Systematic review and meta-analysis of randomized controlled trials. The MEDLINE, EMBASE, and Cochrane Library databases were systematically searched and supplemented with manual searches of PubMed and reference lists. Eligible studies consisted exclusively of randomized controlled trials comparing MS, ACI, or OAT techniques in patients with focal cartilage defects of the knee. The primary outcome of interest was function (Lysholm score, International Knee Documentation Committee score, Knee Osteoarthritis Outcome Score) and pain at 24 months postoperatively. A meta-analysis using standardized mean differences was performed to provide a pooled estimate of effect comparing treatments. A total of 12 eligible randomized trials with a cumulative sample size of 765 patients (62% males) and a mean (±SD) lesion size of 3.9 ± 1.3 cm(2) were included in this review. There were 5 trials comparing ACI with MS, 3 comparing ACI with OAT, and 3 evaluating different generations of ACI. In a pooled analysis comparing ACI with MS, there was no difference in outcomes at 24-month follow-up for function (standardized mean difference, 0.47 [95% CI, -0.19 to 1.13]; P = .16) or pain (standardized mean difference, -0.13 [95% CI, -0.39 to 0.13]; P = .33). The comparisons of ACI to OAT or between different generations of ACI were not amenable to pooled analysis. Overall, 5 of the 6 trials concluded that there was no significant difference in functional outcomes between ACI and OAT or between generations of ACI. There is no significant difference between MS, ACI, and OAT in improving function and pain at intermediate-term follow-up. Further randomized trials with long-term outcomes are warranted. © 2015 The Author(s).

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.

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.

Factors influencing enrollment of African Americans in the Look AHEAD trial.

PubMed

Mount, David L; Davis, Cralen; Kennedy, Betty; Raatz, Susan; Dotson, Kathy; Gary-Webb, Tiffany L; Thomas, Sheikilya; Johnson, Karen C; Espeland, Mark A

2012-02-01

Many factors have been identified that influence the recruitment of African Americans into clinical trials; however, the influence of eligibility criteria may not be widely appreciated. We used the experience from the Look AHEAD (Action for Health in Diabetes) trial screening process to examine the differential impact eligibility criteria had on the enrollment of African Americans compared to other volunteers. Look AHEAD is a large randomized clinical trial to examine whether assignment to an intensive lifestyle intervention designed to produce and maintain weight loss reduces the long-term risk of major cardiovascular events in adults with type 2 diabetes. Differences in the screening, eligibility, and enrollment rates between African Americans and members of other racial/ethnic groups were examined to identify possible reasons. Look AHEAD screened 28,735 individuals for enrollment, including 6226 (21.7%) who were self-identified African Americans. Of these volunteers, 12.9% of the African Americans compared to 19.3% of all other screenees ultimately enrolled (p < 0.001). African Americans no more often than others were lost to follow-up or refused to attend clinic visits to establish eligibility. Furthermore, the enrollment rates of individuals with histories of cardiovascular disease and diabetes therapy did not markedly differ between the ethnic groups. Higher prevalence of adverse levels of blood pressure, heart rate, HbA1c, and serum creatinine among African American screenees accounted for the greater proportions excluded (all p < 0.001). Compared to non-African Americans, African American were more often ineligible for the Look AHEAD trial due to comorbid conditions. Monitoring trial eligibility criteria for differential impact, and modifying them when appropriate, may ensure greater enrollment yields.

Eligibility for clinical trials in primary Sjögren’s syndrome: lessons from the UK Primary Sjögren’s Syndrome Registry

PubMed Central

Oni, Clare; Mitchell, Sheryl; James, Katherine; Ng, Wan-Fai; Griffiths, Bridget; Hindmarsh, Victoria; Price, Elizabeth; Pease, Colin T.; Emery, Paul; Lanyon, Peter; Jones, Adrian; Bombardieri, Michele; Sutcliffe, Nurhan; Pitzalis, Costantino; Hunter, John; Gupta, Monica; McLaren, John; Cooper, Annie; Regan, Marian; Giles, Ian; Isenberg, David; Saravanan, Vadivelu; Coady, David; Dasgupta, Bhaskar; McHugh, Neil; Young-Min, Steven; Moots, Robert; Gendi, Nagui; Akil, Mohammed; Barone, Francesca; Fisher, Ben; Rauz, Saaeha; Richards, Andrea; Bowman, Simon J.

2016-01-01

Abstract Objective: To identify numbers of participants in the UK Primary Sjögren’s Syndrome Registry (UKPSSR) who would fulfil eligibility criteria for previous/current or potential clinical trials in primary SS (pSS) in order to optimize recruitment. Methods: We did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data. Results: In relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sjögren’s Syndrome study (Belimumab), 41.4% fulfilled eligibility for the Trial of Remicade in primary Sjögren’s syndrome study (Infliximab), 35.4% for the Efficacy of Tocilizumab in Primary Sjögren’s Syndrome study (Tocilizumab), 46.3% for the Tolerance and Efficacy of Rituximab in Sjögren’s Disease study (Rituximab), 26.9% for the Trial of anti-B-cell therapy in pSS study (Rituximab) and 26.6% for the Efficacy and Safety of Abatacept in Patients With Primary Sjögren’s Syndrome study (Abatacept). If recent measures of outcome, such as the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) score ⩾5 (measure of patient symptoms) and the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) score ⩾5 (measure of systemic disease activity) are incorporated into a study design, with requirements for an unstimulated salivary flow >0 and anti-Ro positivity, then the pool of eligible participants is reduced to 14.3%. Conclusion: The UKPSSR identified a number of options for trial design, including selection on ESSDAI ⩾5, ESSPRI ⩾5 and serological and other parameters. PMID:26510429

Eligibility for clinical trials in primary Sjögren's syndrome: lessons from the UK Primary Sjögren's Syndrome Registry.

PubMed

Oni, Clare; Mitchell, Sheryl; James, Katherine; Ng, Wan-Fai; Griffiths, Bridget; Hindmarsh, Victoria; Price, Elizabeth; Pease, Colin T; Emery, Paul; Lanyon, Peter; Jones, Adrian; Bombardieri, Michele; Sutcliffe, Nurhan; Pitzalis, Costantino; Hunter, John; Gupta, Monica; McLaren, John; Cooper, Annie; Regan, Marian; Giles, Ian; Isenberg, David; Saravanan, Vadivelu; Coady, David; Dasgupta, Bhaskar; McHugh, Neil; Young-Min, Steven; Moots, Robert; Gendi, Nagui; Akil, Mohammed; Barone, Francesca; Fisher, Ben; Rauz, Saaeha; Richards, Andrea; Bowman, Simon J

2016-03-01

To identify numbers of participants in the UK Primary Sjögren's Syndrome Registry (UKPSSR) who would fulfil eligibility criteria for previous/current or potential clinical trials in primary SS (pSS) in order to optimize recruitment. We did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data. In relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sjögren's Syndrome study (Belimumab), 41.4% fulfilled eligibility for the Trial of Remicade in primary Sjögren's syndrome study (Infliximab), 35.4% for the Efficacy of Tocilizumab in Primary Sjögren's Syndrome study (Tocilizumab), 31.6% for the Tolerance and Efficacy of Rituximab in Sjögren's Disease study (Rituximab), 26.9% for the Trial of anti-B-cell therapy in pSS study (Rituximab) and 26.6% for the Efficacy and Safety of Abatacept in Patients With Primary Sjögren's Syndrome study (Abatacept). If recent measures of outcome, such as the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score ⩾5 (measure of patient symptoms) and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score ⩾5 (measure of systemic disease activity) are incorporated into a study design, with requirements for an unstimulated salivary flow >0 and anti-Ro positivity, then the pool of eligible participants is reduced to 14.3%. The UKPSSR identified a number of options for trial design, including selection on ESSDAI ⩾5, ESSPRI ⩾5 and serological and other parameters. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effective Strategies to Recruit Young Adults Into the TXT2BFiT mHealth Randomized Controlled Trial for Weight Gain Prevention

PubMed Central

Balestracci, Kate; Wong, Annette TY; Hebden, Lana; McGeechan, Kevin; Denney-Wilson, Elizabeth; Harris, Mark F; Phongsavan, Philayrath; Bauman, Adrian; Allman-Farinelli, Margaret

2015-01-01

Background Younger adults are difficult to engage in preventive health, yet in Australia they are gaining more weight and increasing in waist circumference faster than middle-to-older adults. A further challenge to engaging 18- to 35-year-olds in interventions is the limited reporting of outcomes of recruitment strategies. Objective This paper describes the outcomes of strategies used to recruit young adults to a randomized controlled trial (RCT), healthy lifestyle mHealth program, TXT2BFiT, for prevention of weight gain. The progression from enquiry through eligibility check to randomization into the trial and the costs of recruitment strategies are reported. Factors associated with nonparticipation are explored. Methods Participants were recruited either via letters of invitation from general practitioners (GPs) or via electronic or print advertisements, including Facebook and Google—social media and advertising—university electronic newsletters, printed posters, mailbox drops, and newspapers. Participants recruited from GP invitation letters had an appointment booked with their GP for eligibility screening. Those recruited from other methods were sent an information pack to seek approval to participate from their own GP. The total number and source of enquiries were categorized according to eligibility and subsequent completion of steps to enrolment. Cost data and details of recruitment strategies were recorded. Results From 1181 enquiries in total from all strategies, 250 (21.17%) participants were randomized. A total of 5311 invitation letters were sent from 12 GP practices—16 participating GPs. A total of 131 patients enquired with 68 participants randomized (68/74 of those eligible, 92%). The other recruitment methods yielded the remaining 182 randomized participants. Enrolment from print media was 26% of enquiries, from electronic media was 20%, and from other methods was 3%. Across all strategies the average cost of recruitment was Australian Dollar (AUD) $139 per person. The least expensive modality was electronic (AUD $37), largely due to a free feature story on one university Web home page, despite Facebook advertising costing AUD $945 per enrolment. The most expensive was print media at AUD $213 and GP letters at AUD $145 per enrolment. Conclusions The research indicated that free electronic media was the most cost-effective strategy, with GP letters the least expensive of the paid strategies in comparison to the other strategies. This study is an important contribution for future research into efficacy, translation, and implementation of cost-effective programs for the prevention of weight gain in young adults. Procedural frameworks for recruitment protocols are required, along with systematic reporting of recruitment strategies to reduce unnecessary expenditure and allow for valuable public health prevention programs to go beyond the research setting. Trial Registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12612000924853; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362872 (Archived by WebCite at http://www.webcitation.org/6YpNfv1gI). PMID:26048581

Economic support to improve tuberculosis treatment outcomes in South Africa: a pragmatic cluster-randomized controlled trial.

PubMed

Lutge, Elizabeth; Lewin, Simon; Volmink, Jimmy; Friedman, Irwin; Lombard, Carl

2013-05-28

Poverty undermines adherence to tuberculosis treatment. Economic support may both encourage and enable patients to complete treatment. In South Africa, which carries a high burden of tuberculosis, such support may improve the currently poor outcomes of patients on tuberculosis treatment. The aim of this study was to test the feasibility and effectiveness of delivering economic support to patients with pulmonary tuberculosis in a high-burden province of South Africa. This was a pragmatic, unblinded, two-arm cluster-randomized controlled trial, where 20 public sector clinics acted as clusters. Patients with pulmonary tuberculosis in intervention clinics (n = 2,107) were offered a monthly voucher of ZAR120.00 (approximately US$15) until the completion of their treatment. Vouchers were redeemed at local shops for foodstuffs. Patients in control clinics (n = 1,984) received usual tuberculosis care. Intention to treat analysis showed a small but non-significant improvement in treatment success rates in intervention clinics (intervention 76.2%; control 70.7%; risk difference 5.6% (95% confidence interval: -1.2%, 12.3%), P = 0.107). Low fidelity to the intervention meant that 36.2% of eligible patients did not receive a voucher at all, 32.3% received a voucher for between one and three months and 31.5% received a voucher for four to eight months of treatment. There was a strong dose-response relationship between frequency of receipt of the voucher and treatment success (P <0.001). Our pragmatic trial has shown that, in the real world setting of public sector clinics in South Africa, economic support to patients with tuberculosis does not significantly improve outcomes on treatment. However, the low fidelity to the delivery of our voucher meant that a third of eligible patients did not receive it. Among patients in intervention clinics who received the voucher at least once, treatment success rates were significantly improved. Further operational research is needed to explore how best to ensure the consistent and appropriate delivery of such support to those eligible to receive it.

Physical micro-environment interventions for healthier eating in the workplace: protocol for a stepped wedge randomised controlled pilot trial.

PubMed

Vasiljevic, Milica; Cartwright, Emma; Pechey, Rachel; Hollands, Gareth J; Couturier, Dominique-Laurent; Jebb, Susan A; Marteau, Theresa M

2017-01-01

An estimated one third of energy is consumed in the workplace. The workplace is therefore an important context in which to reduce energy consumption to tackle the high rates of overweight and obesity in the general population. Altering environmental cues for food selection and consumption-physical micro-environment or 'choice architecture' interventions-has the potential to reduce energy intake. The first aim of this pilot trial is to estimate the potential impact upon energy purchased of three such environmental cues (size of portions, packages and tableware; availability of healthier vs. less healthy options; and energy labelling) in workplace cafeterias. A second aim of this pilot trial is to examine the feasibility of recruiting eligible worksites, and identify barriers to the feasibility and acceptability of implementing the interventions in preparation for a larger trial. Eighteen worksite cafeterias in England will be assigned to one of three intervention groups to assess the impact on energy purchased of altering (a) portion, package and tableware size ( n  = 6); (b) availability of healthier options ( n  = 6); and (c) energy (calorie) labelling ( n  = 6). Using a stepped wedge design, sites will implement allocated interventions at different time periods, as randomised. This pilot trial will examine the feasibility of recruiting eligible worksites, and the feasibility and acceptability of implementing the interventions in preparation for a larger trial. In addition, a series of linear mixed models will be used to estimate the impact of each intervention on total energy (calories) purchased per time frame of analysis (daily or weekly) controlling for the total sales/transactions adjusted for calendar time and with random effects for worksite. These analyses will allow an estimate of an effect size of each of the three proposed interventions, which will form the basis of the sample size calculations necessary for a larger trial. ISRCTN52923504.

Do Menstrual Hygiene Management Interventions Improve Education and Psychosocial Outcomes for Women and Girls in Low and Middle Income Countries? A Systematic Review

PubMed Central

Hennegan, Julie; Montgomery, Paul

2016-01-01

Background Unhygienic and ineffective menstrual hygiene management has been documented across low resource contexts and linked to negative consequences for women and girls. Objectives To summarise and critically appraise evidence for the effectiveness of menstruation management interventions in improving women and girls’ education, work and psychosocial wellbeing in low and middle income countries. Methods Structured systematic searches were conducted in peer-reviewed and grey literature to identify studies evaluating education and resource provision interventions for menstruation management. Individual and cluster randomised controlled trials were eligible for inclusion, as were non-randomised controlled trials. Study characteristics, outcomes and risk of bias were extracted using a piloted form. Risk of bias was independently assessed by two researchers. Results Eight studies described in ten citations were eligible for inclusion. Studies were highly heterogeneous in design and context. Six included assessment of education-only interventions, and three provided assessment of the provision of different types of sanitary products (menstrual cups, disposable sanitary pads, and reusable sanitary pads). A moderate but non-significant standardised mean difference was found for the two studies assessing the impact of sanitary pad provision on school attendance: 0.49 (95%CI -0.13, 1.11). Included studies were heterogeneous with considerable risk of bias. Trials of education interventions reported positive impacts on menstrual knowledge and practices, however, many studies failed to assess other relevant outcomes. No trials assessed or reported harms. Conclusions There is insufficient evidence to establish the effectiveness of menstruation management interventions, although current results are promising. Eight trials have been conducted, but a high risk of bias was found and clinical heterogeneity precluded synthesis of most results. Whilst trials provided some indication of positive results, further research is needed to establish the role of menstruation hygiene management in education performance, employment and other psychosocial outcomes. This review provides a concise summary of present trials and highlights improvements for future work. PMID:26862750

Specific allergen immunotherapy for the treatment of atopic eczema: a Cochrane systematic review.

PubMed

Tam, H H; Calderon, M A; Manikam, L; Nankervis, H; Núñez, I G; Williams, H C; Durham, S R; Boyle, R J

2016-09-01

Specific allergen immunotherapy (SIT) is an effective allergy treatment, but it is unclear whether SIT is effective for atopic eczema (AE). We undertook a systematic review to assess SIT efficacy and safety for treating AE. We searched databases, ongoing clinical trials registers, and conference proceedings up to July 2015. Randomized controlled trials (RCTs) of SIT using standardized allergen extracts, compared with placebo/control, for treating AE in patients with allergic sensitization were eligible. We identified 12 eligible trials with 733 participants. Interventions included subcutaneous (six trials), sublingual (four trials), oral or intradermal SIT in children/adults allergic to house dust mite (10 trials), grass pollen or other inhalants. Risk of bias was moderate, with high loss to follow-up and nonblinding as the main concerns. For our primary outcomes, three studies (208 participants) reported no significant difference - patient-reported global disease severity improvement RR 0.75 (95% CI 0.45, 1.26); and eczema symptoms mean difference -0.74 on a 20-point scale (95% CI -1.98, 0.50). Two studies (85 participants) reported a significant difference - SIT improved global disease severity RR 2.85 (95% CI 1.02, 7.96); and itch mean difference -4.20 on a 10-point scale (95% CI -3.69, -4.71). Meta-analysis was limited due to extreme statistical heterogeneity. For some secondary outcomes, meta-analyses showed benefits for SIT, for example investigator-rated improvement in eczema severity RR 1.48 (95% CI 1.16, 1.88; six trials, 262 participants). We found no evidence of adverse effects. The overall quality of evidence was low. We found no consistent evidence that SIT is effective for treating AE, but due to the low quality of evidence further research is needed to establish whether SIT has a role in AE treatment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Do Menstrual Hygiene Management Interventions Improve Education and Psychosocial Outcomes for Women and Girls in Low and Middle Income Countries? A Systematic Review.

PubMed

Hennegan, Julie; Montgomery, Paul

2016-01-01

Unhygienic and ineffective menstrual hygiene management has been documented across low resource contexts and linked to negative consequences for women and girls. To summarise and critically appraise evidence for the effectiveness of menstruation management interventions in improving women and girls' education, work and psychosocial wellbeing in low and middle income countries. Structured systematic searches were conducted in peer-reviewed and grey literature to identify studies evaluating education and resource provision interventions for menstruation management. Individual and cluster randomised controlled trials were eligible for inclusion, as were non-randomised controlled trials. Study characteristics, outcomes and risk of bias were extracted using a piloted form. Risk of bias was independently assessed by two researchers. Eight studies described in ten citations were eligible for inclusion. Studies were highly heterogeneous in design and context. Six included assessment of education-only interventions, and three provided assessment of the provision of different types of sanitary products (menstrual cups, disposable sanitary pads, and reusable sanitary pads). A moderate but non-significant standardised mean difference was found for the two studies assessing the impact of sanitary pad provision on school attendance: 0.49 (95%CI -0.13, 1.11). Included studies were heterogeneous with considerable risk of bias. Trials of education interventions reported positive impacts on menstrual knowledge and practices, however, many studies failed to assess other relevant outcomes. No trials assessed or reported harms. There is insufficient evidence to establish the effectiveness of menstruation management interventions, although current results are promising. Eight trials have been conducted, but a high risk of bias was found and clinical heterogeneity precluded synthesis of most results. Whilst trials provided some indication of positive results, further research is needed to establish the role of menstruation hygiene management in education performance, employment and other psychosocial outcomes. This review provides a concise summary of present trials and highlights improvements for future work.

Strategies to support recruitment of patients with life-limiting illness for research: the Palliative Care Research Cooperative Group.

PubMed

Hanson, Laura C; Bull, Janet; Wessell, Kathryn; Massie, Lisa; Bennett, Rachael E; Kutner, Jean S; Aziz, Noreen M; Abernethy, Amy

2014-12-01

The Palliative Care Research Cooperative Group (PCRC) is the first clinical trials cooperative for palliative care in the U.S. To describe barriers and strategies for recruitment during the inaugural PCRC clinical trial. The parent study was a multisite randomized controlled trial enrolling adults with life expectancy anticipated to be one to six months, randomized to discontinue statins (intervention) vs. to continue on statins (control). To study recruitment best practices, we conducted semistructured interviews with 18 site principal investigators (PIs) and clinical research coordinators (CRCs) and reviewed recruitment rates. Interviews covered three topics: 1) successful strategies for recruitment, 2) barriers to recruitment, and 3) optimal roles of the PI and CRC. All eligible site PIs and CRCs completed interviews and provided data on statin protocol recruitment. The parent study completed recruitment of 381 patients. Site enrollment ranged from 1 to 109 participants, with an average of 25 enrolled per site. Five major barriers included difficulty locating eligible patients, severity of illness, family and provider protectiveness, seeking patients in multiple settings, and lack of resources for recruitment activities. Five effective recruitment strategies included systematic screening of patient lists, thoughtful messaging to make research relevant, flexible protocols to accommodate patients' needs, support from clinical champions, and the additional resources of a trials cooperative group. The recruitment experience from the multisite PCRC yields new insights into methods for effective recruitment to palliative care clinical trials. These results will inform training materials for the PCRC and may assist other investigators in the field. Copyright © 2014 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Recruitment and accrual of women in a placebo-controlled clinical pilot study on manual therapy.

PubMed

Cambron, Jerrilyn A; Hawk, Cheryl; Evans, Roni; Long, Cynthia R

2004-06-01

To investigate the accrual rates and recruitment processes among 3 Midwestern sites during a pilot study on manual therapy for chronic pelvic pain. Multisite pilot study for a randomized, placebo-controlled clinical trial. Three chiropractic institutions in or near major metropolitan cities in the Midwestern United States. Thirty-nine women aged 18 to 45 with chronic pelvic pain of at least 6 months duration, diagnosed by a board certified gynecologist. The method of recruitment was collected for each individual who responded to an advertisement and completed an interviewer-administered telephone screen. Participants who were willing and eligible after 3 baseline visits were entered into a randomized clinical trial. The number of responses and accrual rates were determined for the overall study, each of the 3 treatment sites, and each of the 5 recruitment efforts. In this study, 355 women were screened over the telephone and 39 were randomized, making the rate of randomization approximately 10%. The most effective recruitment methods leading to randomization were direct mail (38%) and radio advertisements (34%). However, success of the recruitment process differed by site. Based on the accrual of this multisite pilot study, a full-scale trial would not be feasible using this study's parameters. However, useful information was gained on recruitment effectiveness, eligibility criteria, and screening protocols among the 3 metropolitan sites.

Chronic Use of Theophylline and Mortality in Chronic Obstructive Pulmonary Disease: A Meta-analysis.

PubMed

Horita, Nobuyuki; Miyazawa, Naoki; Kojima, Ryota; Inoue, Miyo; Ishigatsubo, Yoshiaki; Kaneko, Takeshi

2016-05-01

Theophylline has been shown to improve respiratory function and oxygenation in patients with chronic obstruction pulmonary disease (COPD). However, the impact of theophylline on mortality in COPD patients has not been not sufficiently evaluated. Two investigators independently searched for eligible articles in 4 databases. The eligibility criterion for this meta-analysis was an original research article that provided a hazard ratio for theophylline for all-cause mortality of COPD patients. Both randomized controlled trials and observational studies were accepted. After we confirmed no substantial heterogeneity (I(2)<50%), the fixed-model method with generic inverse variance was used for meta-analysis to estimate the pooled hazard ratio. We screened 364 potentially eligible articles. Of the 364 articles, 259 were excluded on the basis of title and abstract, and 99 were excluded after examination of the full text. Our final analysis included 6 observational studies and no randomized controlled trials. One study reported 2 cohorts. The number of patients in each cohort ranged from 47 to 46,403. Heterogeneity (I(2)=42%, P=.11) and publication bias (Begg's test r=0.21, P=.662) were not substantial. Fixed-model meta-analysis yielded a pooled hazard ratio for theophylline for all-cause death of 1.07 (95% confidence interval: 1.02-1.13, P=.003). This meta-analysis of 7 observational cohorts suggests that theophylline slightly increases all-cause death in COPD patients. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Cost-effectiveness of Occupational Therapy in Older People: Systematic Review of Randomized Controlled Trials.

PubMed

Nagayama, Hirofumi; Tomori, Kounosuke; Ohno, Kanta; Takahashi, Kayoko; Yamauchi, Keita

2016-06-01

A systematic review of the cost-effectiveness of occupational therapy for older people was conducted. MEDLINE, CINAHL, Web of Science, PsycINFO, Cochrane Library, OT seeker and unpublished trials registers were searched. Reference lists of all potentially eligible studies were searched with no language restrictions. We included trial-based full economic evaluations that considered both costs and outcomes in occupational therapy for older people compared with standard care (i.e. other therapy) or no intervention. We reviewed each trial for methodological quality using the Cochrane risk of bias tool and assessed the quality of economic evaluations using a Drummond checklist. In the results of this review, we included five eligible studies (1-5) that were randomized controlled trials with high-quality economic evaluation. Two studies were full economic evaluations of interventions for fall prevention (1 and 2); two studies were full economic evaluations of preventive occupational therapy interventions (3 and 4; one was a comparison of an occupational therapy group with a social work group); one study was a full economic evaluation of occupational therapy for individuals with dementia (5). Two of the studies (one was preventive occupational therapy [3] and the other was occupational therapy for dementia [5]) found a significant effect and confirmed the cost-effectiveness of occupational therapy for older people compared with the control group. These studies found that occupational therapy for older people was clinically effective and cost-effective in comparison with standard care or other therapies. With reference to their clinical implication, these intervention studies (using a client-centred approach) suggested potentially cost-effective means to motivate clients to maintain their own health. However, this review has limitations because of the high heterogeneity of the reviewed studies on full economic evaluations of occupational therapy for older people. Future studies on the cost-effectiveness of occupational therapy in older people are strongly warranted. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

What Is the Evidence for Rest, Ice, Compression, and Elevation Therapy in the Treatment of Ankle Sprains in Adults?

PubMed Central

van den Bekerom, Michel P.J; Struijs, Peter A.A; Blankevoort, Leendert; Welling, Lieke; van Dijk, C. Niek; Kerkhoffs, Gino M.M.J

2012-01-01

Context: Ankle sprains are common problems in acute medical care. The variation in treatment observed for the acutely injured lateral ankle ligament complex in the first week after the injury suggests a lack of evidence-based management strategies for this problem. Objective: To analyze the effectiveness of applying rest, ice, compression, and elevation (RICE) therapy begun within 72 hours after trauma for patients in the initial period after ankle sprain. Study Selection: Eligible studies were published original randomized or quasi-randomized controlled trials concerning at least 1 of the 4 subtreatments of RICE therapy in the treatment of acute ankle sprains in adults. Data Sources: MEDLINE, Cochrane Clinical Trial Register, CINAHL, and EMBASE. The lists of references of retrieved publications also were checked manually. Data Extraction: We extracted relevant data on treatment outcome (pain, swelling, ankle mobility or range of motion, return to sports, return to work, complications, and patient satisfaction) and assessed the quality of included studies. If feasible, the results of comparable studies were pooled using fixed- or random-effects models. Data Synthesis: After deduction of the overlaps among the different databases, evaluation of the abstracts, and contact with some authors, 24 potentially eligible trials remained. The full texts of these articles were retrieved and thoroughly assessed as described. This resulted in the inclusion of 11 trials involving 868 patients. The main reason for exclusion was that the authors did not describe a well-defined control group without the intervention of interest. Conclusions: Insufficient evidence is available from randomized controlled trials to determine the relative effectiveness of RICE therapy for acute ankle sprains in adults. Treatment decisions must be made on an individual basis, carefully weighing the relative benefits and risks of each option, and must be based on expert opinions and national guidelines. PMID:22889660

Efficacy and toxicity differences in lung cancer populations in the era of clinical trials globalization: the 'common arm' approach.

PubMed

Mack, Philip C; Gandara, David R; Lara, Primo N

2012-12-01

Historically, notable variability has been observed in clinical trial outcomes between different regions and populations worldwide, even when employing the same cytotoxic regimen in lung cancer. These divergent results underscore the inherent challenges in interpreting trials conducted abroad and raise questions regarding the general applicability of transnational clinical trials. Various reasons have been postulated to account for these differences in efficacy and toxicity, including trial design, eligibility criteria, patient demographics and, perhaps most intriguingly, population-related pharmacogenomics. However, without methodology to control for such variables, these hypotheses remain largely untested. The authors previously developed the 'common arm' approach in order to directly compare efficacy and toxicity results of trials simultaneously performed in different countries. By standardizing clinical trial-associated variables such as treatment regimens (dose, schedule, and so on), eligibility, staging, response and toxicity criteria, this approach has the potential to determine the underlying reasons for divergences in trial outcomes across countries, and whether population-associated polymorphisms contribute to these differences. In the past decade, Japanese and US investigators have applied the common arm analytic method to trials in both extensive-stage small-cell lung cancer (SCLC) and advanced nonSCLC. In the SCLC analysis, a comparison of the cisplatin/irinotecan arms from both trials revealed significant differences in response rates and overall survival. Significant differences were also observed in the distribution of gender and performance status. The common arm analysis in nonSCLC included two trials from Japan and one from the USA, each containing a 'common' carboplatin/paclitaxel arm. Clinical results were similar in the two Japanese trials, but were significantly different from the US trial with regard to survival, neutropenia, febrile neutropenia and anemia. The underlying basis for these divergent outcomes is discussed. The common arm methodology provides a template for identifying and interpreting patient outcome differences across populations, and is an instructive lesson in the burgeoning era of clinical trials globalization.

Oxytocin for preventing postpartum haemorrhage (PPH) in non-facility birth settings.

PubMed

Pantoja, Tomas; Abalos, Edgardo; Chapman, Evelina; Vera, Claudio; Serrano, Valentina P

2016-04-14

Postpartum haemorrhage (PPH) is the single leading cause of maternal mortality worldwide. Most of the deaths associated with PPH occur in resource-poor settings where effective methods of prevention and treatment - such as oxytocin - are not accessible because many births still occur at home, or in community settings, far from a health facility. Likewise, most of the evidence supporting oxytocin effectiveness comes from hospital settings in high-income countries, mainly because of the need of well-organised care for its administration and monitoring. Easier methods for oxytocin administration have been developed for use in resource-poor settings, but as far as we know, its effectiveness has not been assessed in a systematic review. To assess the effectiveness and safety of oxytocin provided in non-facility birth settings by any way in the third stage of labour to prevent PPH. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, the WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov (12 November 2015), and reference lists of retrieved reports. All published, unpublished or ongoing randomised or quasi-randomised controlled trials comparing the administration of oxytocin with no intervention, or usual/standard care for the management of the third stage of labour in non-facility birth settings were considered for inclusion.Quasi-randomised controlled trials and randomised controlled trials published in abstract form only were eligible for inclusion but none were identified. Cross-over trials were not eligible for inclusion in this review. Two review authors independently assessed studies for eligibility, assessed risk of bias and extracted the data using an agreed data extraction form. Data were checked for accuracy. We included one cluster-randomised trial conducted in four rural districts in Ghana that randomised 28 community health officers (CHOs) (serving 2404 potentially eligible pregnant women) to the intervention group and 26 CHOs (serving 3515 potentially eligible pregnant women) to the control group. Overall, the trial had a high risk of bias. CHOs delivered the intervention in the experimental group (injection of 10 IU (international units) of oxytocin in the thigh one minute following birth using a prefilled, auto-disposable syringe). In the control group, CHOs did not provide this prophylactic injection to the women they observed. CHOs had no midwifery skills and did not in any way manage the birth. All other CHO activities (outcome measurement, data collection, and early treatment and referral when necessary) were identical across the control and oxytocin CHOs.Although only one of the nine cases of severe PPH (blood loss greater or equal to 1000 mL) occurred in the oxytocin group, the effect estimate for this outcome was very imprecise and it is uncertain whether the intervention prevents severe PPH (risk ratio (RR) 0.16, 95% confidence interval (CI) 0.02 to 1.30; 1570 women (very low-quality evidence)). Similarly, because of the lack of cases of severe maternal morbidity (e.g. uterine rupture) and maternal deaths, it was not possible to obtain effect estimates for those outcomes (both very low-quality evidence).Oxytocin compared with the control group decreased the incidence of PPH (> 500 mL) in both our unadjusted (RR 0.48, 95% CI 0.28 to 0.81; 1569 women) and adjusted (RR 0.49, 95% CI 0.27 to 0.90; 1174 women (both low-quality evidence)) analyses. There was little or no difference between the oxytocin and control groups on the rates of transfer or referral of the mother to a healthcare facility (RR 0.72, 95% CI 0.34 to 1.56; 1586 women (low-quality evidence)), stillbirths (RR 1.27, 95% CI 0.67 to 2.40; 2006 infants (low-quality evidence)); andearly infant deaths (0 to three days) (RR 1.03, 95% CI 0.35 to 3.07; 1969 infants (low-quality evidence)). There were no cases of needle-stick injury or any other maternal major or minor adverse event or unanticipated harmful event. There were no cases of oxytocin use during labour.There were no data reported for some of this review's secondary outcomes: manual removal of placenta, maternal anaemia, neonatal death within 28 days, neonatal transfer to health facility for advanced care, breastfeeding rates. Similarly, the women's or the provider's satisfaction with the intervention was not reported. It is uncertain if oxytocin administered by CHO in non-facility settings compared with a control group reduces the incidence of severe PPH (>1000 mL), severe maternal morbidity or maternal deaths. However, the intervention probably decreases the incidence of PPH (> 500 mL).The quality of the one trial included in this review was limited because of the risk of attrition and recruitment biases related to limitations in the follow-up of pregnant women in both arms of the trials and some baseline imbalance on the size of babies at birth. Additionally, there was serious imprecision of the effect estimates for most of the primary outcomes mainly because of the size of the trial, very few or no events and CIs around both relative and absolute estimates of effect that include both appreciable benefit and appreciable harm.Although the trial presented data both for primary and secondary outcomes, it seemed to be underpowered to detect differences in the primary outcomes that are the ones more relevant for making judgments about the potential applicability of the intervention in other settings (especially severe PPH).Therefore, taking into account the extreme setting where the intervention was implemented, the limited role of the CHO in the trial and the lack of power for detecting effects on primary (relevant) outcomes, the applicability of the evidence found seems to be rather limited.Further well-executed and adequately-powered randomised controlled trials assessing the effects of using oxytocin in pre-filled injection devices or other new delivery systems (spray-dried ultrafine formulation of oxytocin) on severe PPH are urgently needed. Likewise, other important outcomes like possible adverse events and acceptability of the intervention by mothers and other community stakeholders should also be assessed.

Personalized contact strategies and predictors of time to survey completion: analysis of two sequential randomized trials.

PubMed

Dinglas, Victor D; Huang, Minxuan; Sepulveda, Kristin A; Pinedo, Mariela; Hopkins, Ramona O; Colantuoni, Elizabeth; Needham, Dale M

2015-01-09

Effective strategies for contacting and recruiting study participants are critical in conducting clinical research. In this study, we conducted two sequential randomized controlled trials of mail- and telephone-based strategies for contacting and recruiting participants, and evaluated participant-related variables' association with time to survey completion and survey completion rates. Subjects eligible for this study were survivors of acute lung injury who had been previously enrolled in a 12-month observational follow-up study evaluating their physical, cognitive and mental health outcomes, with their last study visit completed at a median of 34 months previously. Eligible subjects were contacted to complete a new research survey as part of two randomized trials, initially using a randomized mail-based contact strategy, followed by a randomized telephone-based contact strategy for non-responders to the mail strategy. Both strategies focused on using either a personalized versus a generic approach. In addition, 18 potentially relevant subject-related variables (e.g., demographics, last known physical and mental health status) were evaluated for association with time to survey completion. Of 308 eligible subjects, 67% completed the survey with a median (IQR) of 3 (2, 5) contact attempts required. There was no significant difference in the time to survey completion for either randomized trial of mail- or phone-based contact strategy. Among all subject-related variables, age ≤40 years and minority race were independently associated with a longer time to survey completion. We found that age ≤40 years and minority race were associated with a longer time to survey completion, but personalized versus generic approaches to mail- and telephone-based contact strategies had no significant effect. Repeating both mail and telephone contact attempts was important for increasing survey completion rate. NCT00719446.

Experience With Direct-to-Patient Recruitment for Enrollment Into a Clinical Trial in a Rare Disease: A Web-Based Study

PubMed Central

2017-01-01

Background The target sample size for clinical trials often necessitates a multicenter (center of excellence, CoE) approach with associated added complexity, cost, and regulatory requirements. Alternative recruitment strategies need to be tested against this standard model. Objectives The aim of our study was to test whether a Web-based direct recruitment approach (patient-centric, PC) using social marketing strategies provides a viable option to the CoE recruitment method. Methods PC recruitment and Web-based informed consent was compared with CoE recruitment for a randomized controlled trial (RCT) of continuing versus stopping low-dose prednisone for maintenance of remission of patients with granulomatosis with polyangiitis (GPA). Results The PC approach was not as successful as the CoE approach. Enrollment of those confirmed eligible by their physician was 10 of 13 (77%) and 49 of 51 (96%) in the PC and CoE arms, respectively (P=.05). The two approaches were not significantly different in terms of eligibility with 34% of potential participants in the CoE found to be ineligible as compared with 22% in the PC arm (P=.11) nor in provider acceptance, 22% versus 26% (P=.78). There was no difference in the understanding of the trial as reflected in the knowledge surveys of individuals in the PC and CoE arms. Conclusions PC recruitment was substantially less successful than that achieved by the CoE approach. However, the PC approach was good at confirming eligibility and was as acceptable to providers and as understandable to patients as the CoE approach. The PC approach should be evaluated in other clinical settings to get a better sense of its potential. PMID:28246067

Recruitment and enrollment of African Americans into health promoting programs: the effects of health promoting programs on cardiovascular disease risk study.

PubMed

Okhomina, Victoria I; Seals, Samantha R; Marshall, Gailen D

2018-04-03

Randomized controlled trials (RCT) often employ multiple recruitment methods to attract participants, however, special care must be taken to be inclusive of under-represented populations. We examine how recruiting from an existing observational study affected the recruitment of African Americans into a RCT that included yoga-based interventions. In particular, we report the recruitment success of The Effects of Health Promoting Programs (HPP) on Cardiovascular Disease Risk (NCT02019953), the first yoga-based clinical trial to focus only on African Americans. To recruit participants, a multifaceted recruitment strategy was implemented exclusively in the Jackson Heart Study (JHS) cohort. The HPP recruited from the JHS cohort using direct mailings, signs and flyers placed around JHS study facilities, and through JHS annual follow-up interviews. Enrollment into HPP was open to all active JHS participants that were eligible to return for the third clinic exam (n = 4644). The target sample size was 375 JHS participants over a 24 month recruitment and enrollment period. From the active members of the JHS cohort, 503 were pre-screened for eligibility in HPP. More than 90% of those pre-screened were provisionally eligible for the study. The enrollment goal of 375 was completed after a 16-month enrollment period with over 25% (n = 97) of the required sample size enrolling during the second month of recruitment. The findings show that participants in observational studies can be successfully recruited into RCT. Observational studies provide researchers with a well-defined population that may be of interest when designing clinical trials. This is particularly useful in the recruitment of a high-risk, traditionally underrepresented populations for non-pharmacological clinical trials where traditional recruitment methods may prolong enrollment periods and extend study budgets.

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

PubMed

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

2016-06-13

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

ASCOT: a text mining-based web-service for efficient search and assisted creation of clinical trials

PubMed Central

2012-01-01

Clinical trials are mandatory protocols describing medical research on humans and among the most valuable sources of medical practice evidence. Searching for trials relevant to some query is laborious due to the immense number of existing protocols. Apart from search, writing new trials includes composing detailed eligibility criteria, which might be time-consuming, especially for new researchers. In this paper we present ASCOT, an efficient search application customised for clinical trials. ASCOT uses text mining and data mining methods to enrich clinical trials with metadata, that in turn serve as effective tools to narrow down search. In addition, ASCOT integrates a component for recommending eligibility criteria based on a set of selected protocols. PMID:22595088

ASCOT: a text mining-based web-service for efficient search and assisted creation of clinical trials.

PubMed

Korkontzelos, Ioannis; Mu, Tingting; Ananiadou, Sophia

2012-04-30

Clinical trials are mandatory protocols describing medical research on humans and among the most valuable sources of medical practice evidence. Searching for trials relevant to some query is laborious due to the immense number of existing protocols. Apart from search, writing new trials includes composing detailed eligibility criteria, which might be time-consuming, especially for new researchers. In this paper we present ASCOT, an efficient search application customised for clinical trials. ASCOT uses text mining and data mining methods to enrich clinical trials with metadata, that in turn serve as effective tools to narrow down search. In addition, ASCOT integrates a component for recommending eligibility criteria based on a set of selected protocols.

Direct to Public Peer Support and e-Therapy Program Versus Information to Aid Self-Management of Depression and Anxiety: Protocol for a Randomized Controlled Trial

PubMed Central

2017-01-01

Background Regardless of geography or income, effective help for depression and anxiety only reaches a small proportion of those who might benefit from it. The scale of the problem suggests a role for effective, safe, anonymized public health–driven Web-based services such as Big White Wall (BWW), which offer immediate peer support at low cost. Objective Using Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) methodology, the aim of this study was to determine the population reach, effectiveness, cost-effectiveness, and barriers and drivers to implementation of BWW compared with Web-based information compiled by UK’s National Health Service (NHS, NHS Choices Moodzone) in people with probable mild to moderate depression and anxiety disorder. Methods A pragmatic, parallel-group, single-blind randomized controlled trial (RCT) is being conducted using a fully automated trial website in which eligible participants are randomized to receive either 6 months access to BWW or signposted to the NHS Moodzone site. The recruitment of 2200 people to the study will be facilitated by a public health engagement campaign involving general marketing and social media, primary care clinical champions, health care staff, large employers, and third sector groups. People will refer themselves to the study and will be eligible if they are older than 16 years, have probable mild to moderate depression or anxiety disorders, and have access to the Internet. Results The primary outcome will be the Warwick-Edinburgh Mental Well-Being Scale at 6 weeks. We will also explore the reach, maintenance, cost-effectiveness, and barriers and drivers to implementation and possible mechanisms of actions using a range of qualitative and quantitative methods. Conclusions This will be the first fully digital trial of a direct to public online peer support program for common mental disorders. The potential advantages of adding this to current NHS mental health services and the challenges of designing a public health campaign and RCT of two digital interventions using a fully automated digital enrollment and data collection process are considered for people with depression and anxiety. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 12673428; http://www.controlled-trials.com/ISRCTN12673428/12673428 (Archived by WebCite at http://www.webcitation.org/6uw6ZJk5a) PMID:29254909

Double-blind trials in hyperbaric medicine: A narrative review on past experiences and considerations in designing sham hyperbaric treatment.

PubMed

Lansdorp, C A; van Hulst, Rob A

2018-06-01

Background Hyperbaric oxygen therapy, which consists of breathing 100% oxygen under a higher atmospheric pressure than normal, is utilized worldwide in the treatment of several diseases. With the growing demand for evidence-based research, hyperbaric oxygen therapy has been criticized for delivering too little high-quality research, mainly in the form of randomized controlled trials. While not always indispensable, the addition of a sham-controlled group to such a trial can contribute to the quality of the research. However, the design of a sham (hyperbaric) treatment is associated with several considerations regarding adequate blinding and the use of pressure and oxygen. This narrative review discusses information on the sham profile and the blinding and safety of double-blind trials in hyperbaric medicine, irrespective of the indication for treatment. Methods MEDLINE, Embase and CENTRAL were searched for sham-controlled trials on hyperbaric oxygen therapy. The control treatment was considered sham if patients were blinded to their allocation and treatment took place in a hyperbaric chamber, with no restrictions regarding pressurization, oxygen levels or indication. Studies involving children or only one session of hyperbaric oxygen were excluded. Information on (the choice of) treatment profile, blinding measures, patient's perception regarding allocation and safety issues was extracted from eligible studies. Results A total of 42 eligible trials were included. The main strategies for sham treatment were (1) use of a lower pressure than that of the hyperbaric oxygen group, while breathing 21% oxygen; (2) use of the same pressure as the hyperbaric oxygen group, while breathing an adjusted percentage of oxygen; and (3) use of the same pressure as the hyperbaric oxygen group, while breathing 21% oxygen. The advantages and disadvantages of each strategy are discussed using the information provided by the trials. Conclusion Based on this review, using a lower pressure than the hyperbaric oxygen group while breathing 21% oxygen best matches the inertness of the placebo. Although studies show that use of a lower pressure does allow adequate blinding, this is associated with more practical issues than with the other strategies. The choice of which sham profile to use requires careful consideration; moreover, to ensure proper performance, a clear and detailed protocol is also required.

Effect of providing free glasses on children's educational outcomes in China: cluster randomized controlled trial.

PubMed

Ma, Xiaochen; Zhou, Zhongqiang; Yi, Hongmei; Pang, Xiaopeng; Shi, Yaojiang; Chen, Qianyun; Meltzer, Mirjam E; le Cessie, Saskia; He, Mingguang; Rozelle, Scott; Liu, Yizhi; Congdon, Nathan

2014-09-23

To assess the effect of provision of free glasses on academic performance in rural Chinese children with myopia. Cluster randomized, investigator masked, controlled trial. 252 primary schools in two prefectures in western China, 2012-13. 3177 of 19,934 children in fourth and fifth grades (mean age 10.5 years) with visual acuity <6/12 in either eye without glasses correctable to >6/12 with glasses. 3052 (96.0%) completed the study. Children were randomized by school (84 schools per arm) to one of three interventions at the beginning of the school year: prescription for glasses only (control group), vouchers for free glasses at a local facility, or free glasses provided in class. Spectacle wear at endline examination and end of year score on a specially designed mathematics test, adjusted for baseline score and expressed in standard deviations. Among 3177 eligible children, 1036 (32.6%) were randomized to control, 988 (31.1%) to vouchers, and 1153 (36.3%) to free glasses in class. All eligible children would benefit from glasses, but only 15% wore them at baseline. At closeout glasses wear was 41% (observed) and 68% (self reported) in the free glasses group, and 26% (observed) and 37% (self reported) in the controls. Effect on test score was 0.11 SD (95% confidence interval 0.01 to 0.21) when the free glasses group was compared with the control group. The adjusted effect of providing free glasses (0.10, 0.002 to 0.19) was greater than parental education (0.03, -0.04 to 0.09) or family wealth (0.01, -0.06 to 0.08). This difference between groups was significant, but was smaller than the prespecified 0.20 SD difference that the study was powered to detect. The provision of free glasses to Chinese children with myopia improves children's performance on mathematics testing to a statistically significant degree, despite imperfect compliance, although the observed difference between groups was smaller than the study was originally designed to detect. Myopia is common and rarely corrected in this setting.Trial Registration Current Controlled Trials ISRCTN03252665. © Ma et al 2014.

Improving treatment intensification to reduce cardiovascular disease risk: a cluster randomized trial

PubMed Central

2012-01-01

Background Blood pressure, lipid, and glycemic control are essential for reducing cardiovascular disease (CVD) risk. Many health care systems have successfully shifted aspects of chronic disease management, including population-based outreach programs designed to address CVD risk factor control, to non-physicians. The purpose of this study is to evaluate provision of new information to non-physician outreach teams on need for treatment intensification in patients with increased CVD risk. Methods Cluster randomized trial (July 1-December 31, 2008) in Kaiser Permanente Northern California registry of members with diabetes mellitus, prior CVD diagnoses and/or chronic kidney disease who were high-priority for treatment intensification: blood pressure ≥ 140 mmHg systolic, LDL-cholesterol ≥ 130 mg/dl, or hemoglobin A1c ≥ 9%; adherent to current medications; no recent treatment intensification). Randomization units were medical center-based outreach teams (4 intervention; 4 control). For intervention teams, priority flags for intensification were added monthly to the registry database with recommended next pharmacotherapeutic steps for each eligible patient. Control teams used the same database without this information. Outcomes included 3-month rates of treatment intensification and risk factor levels during follow-up. Results Baseline risk factor control rates were high (82-90%). In eligible patients, the intervention was associated with significantly greater 3-month intensification rates for blood pressure (34.1 vs. 30.6%) and LDL-cholesterol (28.0 vs 22.7%), but not A1c. No effects on risk factors were observed at 3 months or 12 months follow-up. Intervention teams initiated outreach for only 45-47% of high-priority patients, but also for 27-30% of lower-priority patients. Teams reported difficulties adapting prior outreach strategies to incorporate the new information. Conclusions Information enhancement did not improve risk factor control compared to existing outreach strategies at control centers. Familiarity with prior, relatively successful strategies likely reduced uptake of the innovation and its potential for success at intervention centers. Trial registration ClinicalTrials.gov Identifier NCT00517686 PMID:22747998

A randomised controlled trial to evaluate the impact of sexual health clinic based automated text message reminders on testing of HIV and other sexually transmitted infections in men who have sex with men in China: protocol for the T2T Study.

PubMed

Zou, Huachun; Meng, Xiaojun; Grulich, Andrew; Huang, Shujie; Jia, Tianjian; Zhang, Xuan; Luo, Zhenzhou; Ding, Yi; Yang, Ligang; Huang, Jinmei; Chen, Weiying; Zheng, Heping; Yang, Bin

2017-07-10

The frequency of screening for HIV and other sexually transmitted infections (STIs) among men who have sex with men (MSM) is still low in China. A sexual health clinic based randomised controlled trial will be conducted in Guangzhou, Wuxi and Shenzhen, China, enrolling 600 MSM. Eligibility will be judged by the pre-programed iPad based questionnaire: (1) age ≥18 years and (2) have had two or more male anal sex partners, or condomless anal sex with a casual male sex partner, or an STI history, in the past 6 months, and (3) provides a valid mobile phone number. Eligible men will be randomly allocated 1:1 to the intervention arm (with monthly text messages reminding them to test for HIV/STIs) or to the control arm (with no reminders). Men in both arms will complete a questionnaire onsite at enrolment and after 12 months, and another questionnaire online at 6 months. Men in both arms will be tested for HIV, syphilis, anal gonorrhoea/chlamydia and penile gonorrhoea/chlamydia at enrolment and at 12 months. The primary outcome is the rate and frequency of HIV testing within the 12 months after enrolment. The secondary outcome is the rate of unprotected anal intercourse. An assessment of the cost effectiveness of this intervention is also planned. The study has been approved by the ethical review committees of the University of New South Wales, Australia (HC16803), the Guangdong Provincial Centre for Skin Disease and STI Control (GDDHLS-20160926) and the Wuxi Centre for Disease Control and Prevention (WXCDC2016009), China. Study findings will be submitted to academic journals and disseminated to local health authorities. Chinese Clinical Trial Registry at: http://www.chictr.org.cn/showprojen.aspx?proj=15752 and WHO International Clinical Trials Registry Platform at: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR-IOR-16009304. © 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.

Comparing community and specialty provider-based recruitment in a randomized clinical trial: clinical trial in fecal incontinence.

PubMed

Whitebird, Robin R; Bliss, Donna Zimmaro; Savik, Kay; Lowry, Ann; Jung, Hans-Joachim G

2010-12-01

Recruitment of participants to clinical trials remains a significant challenge, especially for research addressing topics of a sensitive nature such as fecal incontinence (FI). In the Fiber Study, a randomized controlled trial on symptom management for FI, we successfully enrolled 189 community-living adults through collaborations with specialty-based and community-based settings, each employing methods tailored to the organizational characteristics of their site. Results show that using the two settings increased racial and ethnic diversity of the sample and inclusion of informal caregivers. There were no differential effects on enrollment, final eligibility, or completion of protocol by site. Strategic collaborations with complementary sites can achieve sample recruitment goals for clinical trials on topics that are sensitive or known to be underreported. Copyright © 2010 Wiley Periodicals, Inc.

Accrual and drop out in a primary prevention randomised controlled trial: qualitative study.

PubMed

Eborall, Helen C; Stewart, Marlene C W; Cunningham-Burley, Sarah; Price, Jackie F; Fowkes, F Gerry R

2011-01-11

Recruitment and retention of participants are critical to the success of a randomised controlled trial. Gaining the views of potential trial participants who decline to enter a trial and of trial participants who stop the trial treatment is important and can help to improve study processes. Limited research on these issues has been conducted on healthy individuals recruited for prevention trials in the community. Semi-structured interviews with people who were eligible but had declined to participate in the Aspirin for Asymptomatic Atherosclerosis (AAA) trial (N = 11), and AAA trial participants who had stopped taking the trial medication (N = 11). A focus group with further participants who had stopped taking the trial medication (N = 6). (Total participants N = 28). Explanations for declining to participate could be divided into two groups: the first group were characterised by a lack of necessity to participate and a tendency to prioritise other largely mundane problems. The second group's concern was with a high level of perceived risk from participating.Explanations for stopping trial medication fell into four categories: side effects attributed to the trial medication; starting on aspirin or medication contraindicating to aspirin; experiencing an outcome event, and changing one's mind. These results indicate that when planning trials (especially in preventive medicine) particular attention should be given to designing appropriate recruitment materials and processes that fully inform potential recruits of the risks and benefits of participation. ISRCTN66587262.

BTS randomised feasibility study of active symptom control with or without chemotherapy in malignant pleural mesothelioma: ISRCTN 54469112.

PubMed

Muers, M F; Rudd, R M; O'Brien, M E R; Qian, W; Hodson, A; Parmar, M K B; Girling, D J

2004-02-01

The incidence of mesothelioma is rising rapidly in the UK. There is no generally accepted standard treatment. The BTS recommends active symptom control (ASC). It is not known whether chemotherapy in addition prolongs survival or provides worthwhile palliation with acceptable toxicity. Palliation as recorded by patients has been fully reported for only two regimens: mitomycin, vinblastine, and cisplatin (MVP), and vinorelbine (N). The BTS and collaborators planned to conduct a phase III randomised trial comparing ASC only, ASC+MVP, and ASC+N in 840 patients with survival as the primary outcome measure. The aim of the present study was to assess the acceptability of the trial design to patients and the suitability of two standard quality of life (QL) questionnaires for mesothelioma. Collaborating centres registered all new patients with mesothelioma. Those eligible and giving informed consent completed EORTC QLQ-C30+LC13 and FACT-L QL questionnaires and were randomised between all three or any two of (1) ASC only, (2) ASC+4 cycles of MVP, and (3) ASC+12 weekly doses of N. During 1 year, 242 patients were registered of whom 109 (45%) were randomised (55% of the 197 eligible patients). Fifty two patients from 20 centres were randomised to an option including ASC only. This translates into a rate of 312 per year from 60 centres interested in collaborating in the phase III trial. The EORTC QL questionnaire was superior to FACT-L in terms of completeness of data and patient preference. Clinically relevant palliation was achieved with ASC. The planned phase III trial is feasible.

Pharmacy journal abstracts published in PubMed that abide by the CONsolidated Standards Of Reporting Trials (CONSORT) guidelines

PubMed Central

Blair, Daniel A.; Woolley, Thomas W.

2014-01-01

The purpose of this research was to determine the proportion of abstracts in pharmacy journals that are prepared according to the CONsolidated Standards Of Reporting Trials (CONSORT) criteria for abstracts. Certain abstracts for randomized controlled clinical trials (RCTs) indexed in PubMed were eligible for inclusion, with the primary endpoint being median overall compliance to CONSORT recommendations for abstracts. A total of 63 RCT abstracts were included in the analysis, with only 56% of the recommended CONSORT items represented in the sample. It is recommended that pharmacy journals encourage authors to follow CONSORT recommendations for abstracts when submitting RCTs for publication. PMID:24860268

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.

Can a documentary increase help-seeking intentions in men? A randomised controlled trial

PubMed Central

Schlichthorst, Marisa; Spittal, Matthew J; Phelps, Andrea; Pirkis, Jane

2018-01-01

Background We investigated whether a public health intervention—a three-part documentary called Man Up which explored the relationship between masculinity and mental health, well-being and suicidality—could increase men’s intentions to seek help for personal and emotional problems. Methods We recruited men aged 18 years or over who were not at risk of suicide to participate in a double-blind randomised controlled trial. Participants were randomly assigned (1:1) via computer randomisation to view Man Up (the intervention) or a control documentary. We hypothesised that 4 weeks after viewing Man Up participants would report higher levels of intention to seek help than those who viewed the control documentary. Our primary outcome was assessed using the General Help Seeking Questionnaire, and was analysed for all participants. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616001169437, Universal Trial Number: U1111-1186-1459) and was funded by the Movember Foundation. Results Three hundred and fifty-four men were assessed for eligibility for the trial and randomised to view Man Up or the control documentary. Of these, 337 completed all stages (nine participants were lost to follow-up in the intervention group and eight in the control group). Linear regression analysis showed a significant increase in intentions to seek help in the intervention group, but not in the control group (coef.=2.06, 95% CI 0.48 to 3.63, P=0.01). Conclusions Our trial demonstrates the potential for men’s health outcomes to be positively impacted by novel, media-based public health interventions that focus on traditional masculinity. Trial registration number ACTRN12616001169437, Results. PMID:29101215

Primary Prevention With Statins: ACC/AHA Risk-Based Approach Versus Trial-Based Approaches to Guide Statin Therapy.

PubMed

Mortensen, Martin B; Afzal, Shoaib; Nordestgaard, Børge G; Falk, Erling

2015-12-22

Guidelines recommend initiating primary prevention for atherosclerotic cardiovascular disease (ASCVD) with statins based on absolute ASCVD risk assessment. Recently, alternative trial-based and hybrid approaches were suggested for statin treatment eligibility. This study compared these approaches in a direct head-to-head fashion in a contemporary population. The study used the CGPS (Copenhagen General Population Study) with 37,892 subjects aged 40 to 75 years recruited in 2003 to 2008, all free of ASCVD, diabetes, and statin use at baseline. Among the population studied, 42% were eligible for statin therapy according to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) risk assessment and cholesterol treatment guidelines approach, versus 56% with the trial-based approach and 21% with the hybrid approach. Among these statin-eligible subjects, the ASCVD event rate per 1,000 person-years was 9.8, 6.8, and 11.2, respectively. The ACC/AHA-recommended absolute risk score was well calibrated around the 7.5% 10-year ASCVD risk treatment threshold and discriminated better than the trial-based or hybrid approaches. Compared with the ACC/AHA risk-based approach, the net reclassification index for eligibility for statin therapy among 40- to 75-year-old subjects from the CGPS was -0.21 for the trial-based approach and -0.13 for the hybrid approach. The clinical performance of the ACC/AHA risk-based approach for primary prevention of ASCVD with statins was superior to the trial-based and hybrid approaches. Our results indicate that the ACC/AHA guidelines will prevent more ASCVD events than the trial-based and hybrid approaches, while treating fewer people compared with the trial-based approach. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Intravenous Immunoglobulin in the Therapeutic Armamentarium of Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis

PubMed Central

Sakthiswary, Rajalingham; D’Cruz, David

2014-01-01

Abstract Prepared from the plasma of thousands of blood donors, therapeutic intravenous immunoglobulin (IVIg) mostly consists of human polyspecific immunoglobulin G (IgG). The use of IVIg in systemic lupus erythematosus (SLE) is still considered experimental without any clear indications. The purpose of this systematic review is, therefore, to evaluate the available evidence to determine the therapeutic role of IVIg in SLE. A comprehensive, computerised search was performed in the MEDLINE (Pubmed), Scopus, EMBASE, and Cochrane controlled trials. The study eligibility criteria were randomized controlled trials, and prospective and retrospective observational studies that examined the efficacy of IVIg in adult patients with SLE who were considered the participants. IVIg therapy was the mode of intervention in these patients. Data abstracted included the study design, study population, changes in the disease activity scores (Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure, and Lupus Activity Index-Pregnancy), steroid dose, complement levels, autoantibodies, and renal function. Thereafter, data analysis established statistical procedures for meta-analysis. Thirteen studies (including 3 controlled and 10 observational) were eligible for inclusion. There was significant reduction in the SLE disease activity scores with IVIg therapy with a standard mean difference of 0.584 (P = 0.002, 95% confidence interval [CI] 0.221–0.947). In terms of rise in complement levels, the response rate was 30.9% (P = 0.001, 95 CI 22.1–41.3). The effects of IVIg on other clinical outcome measures including anti-double-stranded DNA, antinuclear antibody, average steroid dose, and renal function could not be determined because of the limited numbers of trials. The limitations of this review were lack of well-designed controlled trials with adequate sample size on the use of IVIg in SLE. In conclusion, the use of IVIg is associated with significant reduction in SLE disease activity and improvement in complement levels. PMID:25310743

Intravenous immunoglobulin in the therapeutic armamentarium of systemic lupus erythematosus: a systematic review and meta-analysis.

PubMed

Sakthiswary, Rajalingham; D'Cruz, David

2014-10-01

Prepared from the plasma of thousands of blood donors, therapeutic intravenous immunoglobulin (IVIg) mostly consists of human polyspecific immunoglobulin G (IgG). The use of IVIg in systemic lupus erythematosus (SLE) is still considered experimental without any clear indications. The purpose of this systematic review is, therefore, to evaluate the available evidence to determine the therapeutic role of IVIg in SLE. A comprehensive, computerised search was performed in the MEDLINE (Pubmed), Scopus, EMBASE, and Cochrane controlled trials. The study eligibility criteria were randomized controlled trials, and prospective and retrospective observational studies that examined the efficacy of IVIg in adult patients with SLE who were considered the participants.IVIg therapy was the mode of intervention in these patients. Data abstracted included the study design, study population, changes in the disease activity scores (Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure, and Lupus Activity Index-Pregnancy), steroid dose, complement levels, autoantibodies, and renal function. Thereafter, data analysis established statistical procedures for meta-analysis. Thirteen studies (including 3 controlled and 10 observational) were eligible for inclusion. There was significant reduction in the SLE disease activity scores with IVIg therapy with a standard mean difference of 0.584 (P = 0.002, 95% confidence interval [CI] 0.221-0.947). In terms of rise in complement levels, the response rate was 30.9% (P = 0.001, 95 CI 22.1-41.3). The effects of IVIg on other clinical outcome measures including anti-double-stranded DNA, antinuclear antibody, average steroid dose, and renal function could not be determined because of the limited numbers of trials. The limitations of this review were lack of well-designed controlled trials with adequate sample size on the use of IVIg in SLE. In conclusion, the use of IVIg is associated with significant reduction in SLE disease activity and improvement in complement levels.

Venous thromboembolism prophylaxis in gynecologic surgery: a systematic review.

PubMed

Rahn, David D; Mamik, Mamta M; Sanses, Tatiana V D; Matteson, Kristen A; Aschkenazi, Sarit O; Washington, Blair B; Steinberg, Adam C; Harvie, Heidi S; Lukban, James C; Uhlig, Katrin; Balk, Ethan M; Sung, Vivian W

2011-11-01

To comprehensively review and critically assess the available gynecologic surgery venous thromboembolism prophylaxis literature and provide clinical practice guidelines. MEDLINE and Cochrane databases from inception to July 2010. We included randomized controlled trials in gynecologic surgery populations. Interventions and comparators included graduated compression stockings, intermittent pneumatic compression, unfractionated heparin, and low molecular weight heparin; placebo and routine postoperative care were allowed as comparators. One thousand two hundred sixty-six articles were screened, and 14 randomized controlled trials (five benign gynecologic, nine gynecologic oncology) met eligibility criteria. In addition, nine prospective or retrospective studies with at least 150 women were identified and provided data on venous thromboembolism risk stratification, gynecologic laparoscopy, and urogynecologic populations. Two reviewers independently screened articles with discrepancies adjudicated by a third. Eligible randomized controlled trials were extracted for these characteristics: study, participant, surgery, intervention, comparator, and outcomes data, including venous thromboembolism incidence and bleeding complications. Studies were individually and collectively assessed for methodologic quality and strength of evidence. Overall incidence of clinical venous thromboembolism was 0-2% in the benign gynecologic population. With use of intermittent pneumatic compression for benign major procedures, venous thromboembolism incidence was less than 1%. No venous thromboembolisms were identified in prospective studies of benign laparoscopic procedures. Overall quality of evidence in the benign gynecologic literature was poor. Gynecologic-oncology randomized controlled trials reported venous thromboembolism incidence (including "silent" venous thromboembolisms) of 0-14.8% with prophylaxis and up to 34.6% without prophylaxis. Fair quality of evidence supports that unfractionated heparin and intermittent pneumatic compression are both superior to placebo or no intervention but insufficient to determine whether heparins are superior to intermittent pneumatic compression for venous thromboembolism prevention. Combining two of three risks (aged 60 years or older, cancer, or personal venous thromboembolism history) substantially elevated the risk of venous thromboembolism. Intermittent pneumatic compression provides sufficient prophylaxis for the majority of gynecology patients undergoing benign surgery. Additional risk factors warrant the use of combined mechanical and pharmacologic prophylaxis.

A structured training programme for caregivers of inpatients after stroke (TRACS): a cluster randomised controlled trial and cost-effectiveness analysis.

PubMed

Forster, Anne; Dickerson, Josie; Young, John; Patel, Anita; Kalra, Lalit; Nixon, Jane; Smithard, David; Knapp, Martin; Holloway, Ivana; Anwar, Shamaila; Farrin, Amanda

2013-12-21

Most patients who have had a stroke are dependent on informal caregivers for activities of daily living. The TRACS trial investigated a training programme for caregivers (the London Stroke Carers Training Course, LSCTC) on physical and psychological outcomes, including cost-effectiveness, for patients and caregivers after a disabling stroke. We undertook a pragmatic, multicentre, cluster randomised controlled trial with a parallel cost-effectiveness analysis. Stroke units were eligible if four of five criteria used to define a stroke unit were met, a substantial number of patients on the unit had a diagnosis of stroke, staff were able to deliver the LSCTC, and most patients were discharged to a permanent place of residence. Stroke units were randomly assigned to either LSCTC or usual care (control group), stratified by geographical region and quality of care, and using blocks of size 2. Patients with a diagnosis of stroke, likely to return home with residual disability and with a caregiver providing support were eligible. The primary outcome for patients was self-reported extended activities of daily living at 6 months, measured with the Nottingham Extended Activities of Daily Living (NEADL) scale. The primary outcome for caregivers was self-reported burden at 6 months, measured with the caregivers burden scale (CBS). We combined patient and caregiver costs with primary outcomes and quality-adjusted life-years (QALYs) to assess cost-effectiveness. This trial is registered with controlled-trials.com, number ISRCTN 49208824. We assessed 49 stroke units for eligibility, of which 36 were randomly assigned to either the intervention group or the control group. Between Feb 27, 2008, and Feb 9, 2010, 928 patient and caregiver dyads were registered, of which 450 were in the intervention group, and 478 in the control group. Patients' self-reported extended activities of daily living did not differ between groups at 6 months (adjusted mean NEADL score 27·4 in the intervention group versus 27·6 in the control group, difference -0·2 points [95% CI -3·0 to 2·5], p value=0·866, ICC=0·027). The caregiver burden scale did not differ between groups either (adjusted mean CBS 45·5 in the intervention group versus 45·0 in the control group, difference 0·5 points [95% CI -1·7 to 2·7], p value=0·660, ICC=0·013). Patient and caregiver costs were similar in both groups (length of the initial stroke admission and associated costs were £13,127 for the intervention group and £12,471 for the control group; adjusted mean difference £1243 [95% CI -1533 to 4019]; p value=0·380). Probabilities of cost-effectiveness based on QALYs were low. In a large scale, robust evaluation, results from this study have shown no differences between the LSCTC and usual care on any of the assessed outcomes. The immediate period after stroke might not be the ideal time to deliver structured caregiver training. Medical Research Council. Copyright © 2013 Elsevier Ltd. All rights reserved.

Clinical efficacy of edaravone for the treatment of amyotrophic lateral sclerosis.

PubMed

Sawada, Hideyuki

2017-05-01

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disease. Although the pathogenesis remains unresolved, oxidative stress is known to play a pivotal role. Edaravone works in the central nervous system as a potent scavenger of oxygen radicals. In ALS mouse models, edaravone suppresses motor functional decline and nitration of tyrosine residues in the cerebrospinal fluid. Areas covered: Three clinical trials, one phase II open-label trial, and two phase III placebo-control randomized trials were reviewed. In all trials, the primary outcome measure was the changes in scores on the revised ALS functional rating scale (ALSFRS-R) to evaluate motor function of patients. Expert opinion: The phase II open label trial suggested that edaravone is safe and effective in ALS, markedly reducing 3-nitrotyrosine levels in the cerebrospinal fluid. One of the two randomized controlled trials showed beneficial effects in ALSFRS-R, although the differences were not significant. The last trial demonstrated that edaravone provided significant efficacy in ALSFRS-R scores over 24 weeks where concomitant use of riluzole was permitted. Eligibility was restricted to patients with a relatively short disease duration and preserved vital capacity. Therefore, combination therapy with edaravone and riluzole should be considered earlier.

The Clinical Effects of Aromatherapy Massage on Reducing Pain for the Cancer Patients: Meta-Analysis of Randomized Controlled Trials.

PubMed

Chen, Ting-Hao; Tung, Tao-Hsin; Chen, Pei-Shih; Wang, Shu-Hui; Chao, Chuang-Min; Hsiung, Nan-Hsing; Chi, Ching-Chi

2016-01-01

Purpose. Aromatherapy massage is an alternative treatment in reducing the pain of the cancer patients. This study was to investigate whether aromatherapy massage could improve the pain of the cancer patients. Methods. We searched PubMed and Cochrane Library for relevant randomized controlled trials without language limitations between 1 January 1990 and 31 July 2015 with a priori defined inclusion and exclusion criteria. The search terms included aromatherapy, essential oil, pain, ache, cancer, tumor, and carcinoma. There were 7 studies which met the selection criteria and 3 studies were eventually included among 63 eligible publications. Results. This meta-analysis included three randomized controlled trials with a total of 278 participants (135 participants in the massage with essential oil group and 143 participants in the control (usual care) group). Compared with the control group, the massage with essential oil group had nonsignificant effect on reducing the pain (standardized mean difference = 0.01; 95% CI [-0.23,0.24]). Conclusion. Aromatherapy massage does not appear to reduce pain of the cancer patients. Further rigorous studies should be conducted with more objective measures.

A Meta-Analysis Comparing Liposomal Bupivacaine and Traditional Periarticular Injection for Pain Control after Total Knee Arthroplasty.

PubMed

Sun, Hao; Huang, Zhiyu; Zhang, Zhiqi; Liao, Weiming

2018-04-04

Liposomal bupivacaine is a novel method for pain control after total knee arthroplasty (TKA), but recent studies showed no advantage for patients undergoing TKA compared with traditional periarticular injection (PAI). The purpose of this analysis was to compare the clinical outcomes between liposomal bupivacaine treatment and traditional PAI. We retrospectively reviewed data from 16 clinical trials in published databases from their inception to June 2017. The primary outcome was postoperative Visual Analogue Scale (VAS) score and secondary outcomes included opiate usage, narcotic consumption, range of motion, and length of stay. Nine randomized controlled trials and seven nonrandomized controlled trials involving 924 liposomal bupivacaine cases and 1,293 traditional PAI cases were eligible for inclusion in the meta-analysis. No differences were detected in most of the clinical outcomes, except for postoperative VAS within 12 hours and length of stay. This analysis showed that liposomal bupivacaine is not associated with significant improvement in postoperative pain control or other outcomes in TKA compared with PAI. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Study protocol: a cluster randomised controlled trial of a school based fruit and vegetable intervention – Project Tomato

PubMed Central

Kitchen, Meaghan S; Ransley, Joan K; Greenwood, Darren C; Clarke, Graham P; Conner, Mark T; Jupp, Jennifer; Cade, Janet E

2009-01-01

Background The School Fruit and Vegetable Scheme (SFVS) is an important public health intervention. The aim of this scheme is to provide a free piece of fruit and/or vegetable every day for children in Reception to Year 2. When children are no longer eligible for the scheme (from Year 3) their overall fruit and vegetable consumption decreases back to baseline levels. This proposed study aims to design a flexible multi-component intervention for schools to support the maintenance of fruit and vegetable consumption for Year 3 children who are no longer eligible for the scheme. Method This study is a cluster randomised controlled trial of Year 2 classes from 54 primary schools across England. The schools will be randomly allocated into two groups to receive either an active intervention called Project Tomato, to support maintenance of fruit intake in Year 3 children, or a less active intervention (control group), consisting of a 5 A DAY booklet. Children's diets will be analysed using the Child And Diet Evaluation Tool (CADET), and height and weight measurements collected, at baseline (Year 2) and 18 month follow-up (Year 4). The primary outcome will be the ability of the intervention (Project Tomato) to maintain consumption of fruit and vegetable portions compared to the control group. Discussion A positive result will identify how fruit and vegetable consumption can be maintained in young children, and will be useful for policies supporting the SFVS. A negative result would be used to inform the research agenda and contribute to redefining future strategies for increasing children's fruit and vegetable consumption. Trial registration Medical Research Council Registry code G0501297 PMID:19531246

Differences in Functional Outcomes for Adult Patients with Prosthodontically-Treated and -Untreated Shortened Dental Arches: A Systematic Review

PubMed Central

Khan, Saadika; Musekiwa, Alfred; Chikte, Usuf M. E.; Omar, Ridwaan

2014-01-01

This review examined differences in functional outcomes and patient satisfaction when shortened dental arches are left untreated compared to their restoration to complete arch lengths with different prosthodontic interventions. Methods A protocol was developed according to the criteria for a systematic review. All relevant databases were searched to identify appropriate clinical trials regardless of language or publication status. Predetermined eligibility criteria were applied, trial quality assessed and data extracted for each study. Relevant outcomes assessed were: functioning ability, patient satisfaction and harmful effects on oral structures. Results Searches yielded 101 articles: 81 from electronic databases and 20 from reference lists of retrieved articles (PEARLing searches). Sixty-nine citations were assessed for eligibility after removing 32 duplicate records. After reading titles and abstracts, a total of 41 records were excluded and the full-texts of the remaining 28 records were read. Only 21 records were included for the SR because 7 records were excluded after reading the full-text reports. These 21 records report the outcomes of four randomized controlled trials (RCTs) and one non-randomized clinical trial (CT) which were pre-specified and used for this review. No on-going studies were found and no eligible studies were excluded for failure to report the reviewer’s pre-specified outcomes. Outcomes were reported in the retrieved 21 articles. A narrative explanation of the pre-specified outcomes is reported for the 3 comparison groups (which were based on the different interventions used for the individual clinical trials). The shortened dental arch as a treatment option is encouraging in terms of functioning, patient satisfaction and cost-effectiveness. By using only high quality studies it was expected that the results would be more reliable when making conclusions and recommendations, but some of the included studies had to be downgraded due to methodological errors. PMID:24992473

Impact of exclusion criteria for the DASISION and ENESTnd trials in the front-line treatment of a 'real-life' patient population with chronic myeloid leukaemia.

PubMed

Latagliata, Roberto; Carmosino, Ida; Vozella, Federico; Volpicelli, Paola; De Angelis, Federico; Loglisci, Maria Giovanna; Salaroli, Adriano; De Luca, Maria Lucia; Montagna, Chiara; Serrao, Alessandra; Molica, Matteo; Diverio, Daniela; Nanni, Mauro; Mancini, Marco; Breccia, Massimo; Alimena, Giuliana

2017-06-01

Both Dasision and ENESTnd trials had many exclusion criteria, with a possible selection bias compared with the real-life. To address the impact of this bias on the first-line treatment in the current clinical practice, we revised 207 unselected newly diagnosed chronic phase chronic myeloid leukaemia (CML) patients [M/F 108/99, median age 58.8 years, interquartile range 42.3-70.2] treated with front-line imatinib from June 2002 to June 2013 at our Institution, and evaluated how many of them would have been excluded from enrolment in the two trials. Twenty-eight patients (13.5%) should have been excluded by both trials because of polycomorbidities (12), severe cardiomyopathy (five), age > 80 with frailty (three), drug abuse (two) or other severe concomitant diseases (six). In addition, eight patients should have been excluded by Dasision due to isolated chronic obstructive broncopulmonar disease, and 19 patients should have been excluded by ENESTnd due to isolated diabetes (10), arrhythmia (four), acute myocardial infarction > 6 months before CML diagnosis (two), chronic pancreatic disease (two) and peripheral arterial obstructive disease (one). On the whole, 36 patients (17.4%) would have been excluded by Dasision trial and 47 (22.7%) by ENESTnd trial. The patients potentially not eligible for both trials were significantly older and with imatinib had a worse outcome compared with patients potentially eligible. Our data highlight that an automatic transposition of results available in clinical controlled trials into the frontline real-life management of CML patients should be regarded with caution. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Preoperative intra-aortic balloon pump in patients undergoing coronary bypass surgery: a systematic review and meta-analysis.

PubMed

Dyub, Adel M; Whitlock, Richard P; Abouzahr, Labib L; Cinà, Claudio S

2008-01-01

To assess the effectiveness of preoperative intra-aortic balloon pump (IABP) placement in high-risk patients undergoing coronary bypass surgery (CABG). The primary outcome was hospital mortality and secondary outcomes were IABP-related complications (bleeding, leg ischemia, aortic dissection). MEDLINE, EMBASE, Cochrane registry of Controlled Trials, and reference lists of relevant articles were searched. We included randomized controlled trials (RCTs), and cohort studies that fulfilled our a priori inclusion criteria. Eligibility decisions, relevance, study validity, and data extraction were performed in duplicate using pre-specified criteria. Meta-analysis was conducted using a random effects model. Ten publications fulfilled our eligibility criteria, of which four were RCTs and six were cohort studies with controls. There were statistical as well as clinical heterogeneity among included studies. A total of 1034 patients received preoperative IABP and 1329 did not receive preoperative IABP. The pooled odds ratio (OR) for hospital mortality in patients treated with preoperative IABP was 0.41 (95% CI, 0.21-0.82, p = 0.01). The number needed to treat was 17. The pooled OR for hospital mortality from randomized trials was 0.18 (95% CI, 0.06-0.57, p = 0.003) and from cohort studies was 0.54 (95% CI, 0.24-1.2, p = 0.13). Overall, 3.7% (13 of 349) of patients who received preoperative IABP developed either limb ischemia or haematoma at the IABP insertion site, and most of these complications improved after discontinuation of IABP. Evidence from this meta-analysis support the use of preoperative IABP in high-risk patients to reduce hospital mortality.

Why is recruitment to trials difficult? An investigation into recruitment difficulties in an RCT of supported employment in patients with severe mental illness

PubMed Central

Howard, Louise; de Salis, Isabel; Tomlin, Zelda; Thornicroft, Graham; Donovan, Jenny

2009-01-01

Background Under-recruitment to randomised controlled trials (RCTs) is often problematic and there may be particular difficulties in recruiting patients with severe mental illness. Aim To evaluate reasons for under-recruitment in an RCT of patients with severe mental illness Methods Qualitative study during the recruitment phase of an RCT of supported employment. Trial staff and recruiting clinicians were interviewed. Data were analyzed thematically using constant comparative techniques. Results Recruitment rates were low. Five main reasons for recruitment difficulties were found. These included: (i) misconceptions about trials, (ii) lack of equipoise, (iii) misunderstanding of the trial arms, (iv) variable interpretations of eligibility criteria, (v) paternalism. Conclusion Reasons for recruitment difficulties in trials involving patients with severe mental illness include issues that occur in trials in general, but others are more specific to these patients. Clinician and patient involvement in the study design may improve recruitment in future similar trials. PMID:18718555

Intensive Versus Standard Blood Pressure Control in SPRINT-Eligible Participants of ACCORD-BP.

PubMed

Buckley, Leo F; Dixon, Dave L; Wohlford, George F; Wijesinghe, Dayanjan S; Baker, William L; Van Tassell, Benjamin W

2017-12-01

We sought to determine the effect of intensive blood pressure (BP) control on cardiovascular outcomes in participants with type 2 diabetes mellitus (T2DM) and additional risk factors for cardiovascular disease (CVD). This study was a post hoc, multivariate, subgroup analysis of ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure) participants. Participants were eligible for the analysis if they were in the standard glucose control arm of ACCORD-BP and also had the additional CVD risk factors required for SPRINT (Systolic Blood Pressure Intervention Trial) eligibility. We used a Cox proportional hazards regression model to compare the effect of intensive versus standard BP control on CVD outcomes. The "SPRINT-eligible" ACCORD-BP participants were pooled with SPRINT participants to determine whether the effects of intensive BP control interacted with T2DM. The mean baseline Framingham 10-year CVD risk scores were 14.5% and 14.8%, respectively, in the intensive and standard BP control groups. The mean achieved systolic BP values were 120 and 134 mmHg in the intensive and standard BP control groups ( P < 0.001). Intensive BP control reduced the composite of CVD death, nonfatal myocardial infarction (MI), nonfatal stroke, any revascularization, and heart failure (hazard ratio 0.79; 95% CI 0.65-0.96; P = 0.02). Intensive BP control also reduced CVD death, nonfatal MI, and nonfatal stroke (hazard ratio 0.69; 95% CI 0.51-0.93; P = 0.01). Treatment-related adverse events occurred more frequently in participants receiving intensive BP control (4.1% vs. 2.1%; P = 0.003). The effect of intensive BP control on CVD outcomes did not differ between patients with and without T2DM ( P > 0.62). Intensive BP control reduced CVD outcomes in a cohort of participants with T2DM and additional CVD risk factors. © 2017 by the American Diabetes Association.

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.

Effectiveness of mobile health (mHealth) interventions for promoting healthy eating in adults: A systematic review.

PubMed

McCarroll, Rebecca; Eyles, Helen; Ni Mhurchu, Cliona

2017-12-01

Unhealthy eating is a major risk factor for chronic disease. However, many current strategies to promote healthy eating are not sustainable over the longer-term. More cost-effective wide-reaching initiatives are urgently needed. Mobile health (mHealth) interventions, delivered via mobile devices, could provide a solution. This systematic review summarized the evidence on the effect of mHealth interventions for promoting healthy eating in adults. A comprehensive systematic search of five scientific databases was conducted using methods adapted from the Cochrane Handbook. Eligible studies were randomized controlled trials (RCTs), published up to 1 July 2016, which examined healthy eating interventions delivered via mobile device. Of 879 articles identified, 84 full text articles were potentially eligible and further assessed, and 23 included. Narrative review results indicated small positive effects of mHealth interventions on healthy eating (5/8 trials) and weight loss (5/13 trials). However, the current evidence base is insufficient (studies are of poor quality) to determine conclusive positive effects. More rigorous RCTs with longer-term (>6months) follow-up are warranted to determine if effects are maintained. Copyright © 2017 Elsevier Inc. All rights reserved.

Mindfulness-based stress reduction for treating chronic headache: A systematic review and meta-analysis.

PubMed

Anheyer, Dennis; Leach, Matthew J; Klose, Petra; Dobos, Gustav; Cramer, Holger

2018-01-01

Background Mindfulness-based stress reduction/cognitive therapy are frequently used for pain-related conditions, but their effects on headache remain uncertain. This review aimed to assess the efficacy and safety of mindfulness-based stress reduction/cognitive therapy in reducing the symptoms of chronic headache. Data sources and study selection MEDLINE/PubMed, Scopus, CENTRAL, and PsychINFO were searched to 16 June 2017. Randomized controlled trials comparing mindfulness-based stress reduction/cognitive therapy with usual care or active comparators for migraine and/or tension-type headache, which assessed headache frequency, duration or intensity as a primary outcome, were eligible for inclusion. Risk of bias was assessed using the Cochrane Tool. Results Five randomized controlled trials (two on tension-type headache; one on migraine; two with mixed samples) with a total of 185 participants were included. Compared to usual care, mindfulness-based stress reduction/cognitive therapy did not improve headache frequency (three randomized controlled trials; standardized mean difference = 0.00; 95% confidence interval = -0.33,0.32) or headache duration (three randomized controlled trials; standardized mean difference = -0.08; 95% confidence interval = -1.03,0.87). Similarly, no significant difference between groups was found for pain intensity (five randomized controlled trials; standardized mean difference = -0.78; 95% confidence interval = -1.72,0.16). Conclusions Due to the low number, small scale and often high or unclear risk of bias of included randomized controlled trials, the results are imprecise; this may be consistent with either an important or negligible effect. Therefore, more rigorous trials with larger sample sizes are needed.

Yoga for Health Care in Korea: A Protocol for Systematic Review of Clinical Trials.

PubMed

Choi, Jiae; Jun, Ji Hee; Lee, Ju Ah; Lee, Myeong Soo

2016-08-01

This systematic review aims to evaluate the therapeutic effects of yoga therapy using an evidence-based approach and investigates the relationship between yoga and the meridian energies based on all available clinical studies in Korea. Sixteen electronic databases will be searched from the inception of the study until January 2016. All clinical evidences that evaluate any type of yoga and any type of control in individuals with any type of condition will be eligible. The methodological quality will be assessed using the Cochrane risk of bias tool for randomized clinical trials and the Newcastle-Ottawa scale for nonrandomized studies. Two authors will independently assess each study for eligibility and the risk of bias, and then they will extract the data. With its extensive, unbiased search of the Korean literature from various databases without any language restrictions, this systematic review will be useful for both practitioners in the field of yoga research as well as for patients. Copyright © 2016. Published by Elsevier B.V.

A multicentre randomized controlled trial of gentle assisted pushing in the upright posture (GAP) or upright posture alone compared with routine practice to reduce prolonged second stage of labour (the Gentle Assisted Pushing study): study protocol.

PubMed

Hofmeyr, G Justus; Singata, Mandisa; Lawrie, Theresa; Vogel, Joshua P; Landoulsi, Sihem; Seuc, Armando H; Gülmezoglu, A Metin

2015-12-16

Fundal pressure (pushing on the upper part of the uterus in the direction of the birth canal) is often performed in routine practice, however the benefit and indications for its use are unclear and vigorous pressure is potentially harmful. There is some evidence that it may be applied routinely or to expedite delivery in some situations (e.g. fetal distress or maternal exhaustion), particularly in settings where other methods of achieving delivery (forceps, vacuum) are not available. Gentle assisted pushing (GAP) is an innovative method of applying gentle but steady pressure to the uterine fundus with the woman in an upright posture. This trial aims to evaluate the use of GAP in an upright posture, or upright posture alone, on reducing the mean time of delivery and the associated maternal and neonatal complications in women not having delivered following 15-30 min in the second stage of labour. We will conduct a multicentre, randomized, unblinded, controlled trial with three parallel arms (1:1:1). 1,145 women will be randomized at three hospitals in South Africa. Women will be eligible for inclusion if they are ≥18 years old, nulliparous, gestational age ≥ 35 weeks, have a singleton pregnancy in cephalic presentation and vaginal delivery anticipated. Women with chronic medical conditions or obstetric complications are not eligible. If eligible women are undelivered following 15-30 min in the second stage of labour, they will be randomly assigned to: 1) GAP in the upright posture, 2) upright posture only and 3) routine practice (recumbent/supine posture). The primary outcome is the mean time from randomization to complete delivery. Secondary outcomes include operative delivery, adverse neonatal outcomes, maternal adverse events and discomfort. This trial will establish whether upright posture and/or a controlled method of applying fundal pressure (GAP) can improve labour outcomes for women and their babies. If fundal pressure is found to have a measurable beneficial effect, this gentle approach can be promoted as a replacement for the uncontrolled methods currently in use. If it is not found to be useful, fundal pressure can be discouraged.

Generalizability of Clinical Trial Results for Adolescent Major Depressive Disorder.

PubMed

Blanco, Carlos; Hoertel, Nicolas; Franco, Silvia; Olfson, Mark; He, Jian-Ping; López, Saioa; González-Pinto, Ana; Limosin, Frédéric; Merikangas, Kathleen R

2017-12-01

Although there have been a number of clinical trials evaluating treatments for adolescents with major depressive disorder (MDD), the generalizability of those trials to samples of depressed adolescents who present for routine clinical care is unknown. Examining the generalizability of clinical trials of pharmacological and psychotherapy interventions for adolescent depression can help administrators and frontline practitioners determine the relevance of these studies for their patients and may also guide eligibility criteria for future clinical trials in this clinical population. Data on nationally representative adolescents were derived from the National Comorbidity Survey: Adolescent Supplement. To assess the generalizability of adolescent clinical trials for MDD, we applied a standard set of eligibility criteria representative of clinical trials to all adolescents in the National Comorbidity Survey: Adolescent Supplement with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD ( N = 592). From the overall MDD sample, 61.9% would have been excluded from a typical pharmacological trial, whereas 42.2% would have been excluded from a psychotherapy trial. Among those who sought treatment ( n = 412), the corresponding exclusion rates were 72.7% for a pharmacological trial and 52.2% for a psychotherapy trial. The criterion leading to the largest number of exclusions was "significant risk of suicide" in both pharmacological and psychotherapy trials. Pharmacological and, to a lesser extent, psychotherapy clinical trials likely exclude most adolescents with MDD. Careful consideration should be given to balancing eligibility criteria and internal validity with applicability in routine clinical care while ensuring patient safety. Copyright © 2017 by the American Academy of Pediatrics.

Baduanjin Exercise for Stroke Rehabilitation: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

PubMed Central

Wang, Chaoyi; Chen, Xiaoan; Wang, Huiru

2018-01-01

Objective: The purpose of this review was to objectively evaluate the effects of Baduanjin exercise on rehabilitative outcomes in stroke patients. Methods: Both Chinese and English electronic databases were searched for potentially relevant trials. Two review authors independently screened eligible trials against the inclusion criteria, extracted data, and assessed the methodological quality by using the revised PEDro scale. Meta-analysis was only performed for balance function. Results: In total, there were eight randomized controlled trials selected in this systematic review. The aggregated result of four trials has shown a significant benefit in favor of Baduanjin on balance function (Hedges’ g = 2.39, 95% CI 2.14 to 2.65, p < 0.001, I2 = 61.54). Additionally, Baduanjin exercise effectively improved sensorimotor function of lower extremities and ability of daily activities as well as reduced depressive level, leading to improved quality of life. Conclusion: Baduanjin exercise as an adjunctive and safe method may be conducive to help stroke patients achieve the best possible short-term outcome and should be integrated with mainstream rehabilitation programs. More rigorous randomized controlled trials with long-term intervention periods among a large sample size of stroke patients are needed to draw a firm conclusion regarding the rehabilitative effects for this population. PMID:29584623

Piezoelectric Versus Conventional Rotary Techniques for Impacted Third Molar Extraction: A Meta-analysis of Randomized Controlled Trials.

PubMed

Jiang, Qian; Qiu, Yating; Yang, Chi; Yang, Jingyun; Chen, Minjie; Zhang, Zhiyuan

2015-10-01

Impacted third molars are frequently encountered in clinical work. Surgical removal of impacted third molars is often required to prevent clinical symptoms. Traditional rotary cutting instruments are potentially injurious, and piezosurgery, as a new osteotomy technique, has been introduced in oral and maxillofacial surgery. No consistent conclusion has been reached regarding whether this new technique is associated with fewer or less severe postoperative sequelae after third molar extraction.The aim of this study was to compare piezosurgery with rotary osteotomy techniques, with regard to surgery time and the severity of postoperative sequelae, including pain, swelling, and trismus.We conducted a systematic literature search in the Cochrane Library, PubMed, Embase, and Google Scholar.The eligibility criteria of this study included the following: the patients were clearly diagnosed as having impacted mandibular third molars; the patients underwent piezosurgery osteotomy, and in the control group rotary osteotomy techniques, for removing impacted third molars; the outcomes of interest include surgery time, trismus, swelling or pain; the studies are randomized controlled trials.We used random-effects models to calculate the difference in the outcomes, and the corresponding 95% confidence interval. We calculated the weighted mean difference if the trials used the same measurement, and a standardized mean difference if otherwise.A total of seven studies met the eligibility criteria and were included in our analysis. Compared with rotary osteotomy, patients undergoing piezosurgery experienced longer surgery time (mean difference 4.13 minutes, 95% confidence interval 2.75-5.52, P < 0.0001). Patients receiving the piezoelectric technique had less swelling at postoperative days 1, 3, 5, and 7 (all Ps ≤0.023). Additionally, there was a trend of less postoperative pain and trismus in the piezosurgery groups.The number of included randomized controlled trials and the sample size of each trial were relatively small, double blinding was not possible, and cost analysis was unavailable due to a lack of data.Our meta-analysis indicates that although patients undergoing piezosurgery experienced longer surgery time, they had less postoperative swelling, indicating that piezosurgery is a promising alternative technique for extraction of impacted third molars.

Effectiveness and cost-effectiveness of a very brief physical activity intervention delivered in NHS Health Checks (VBI Trial): study protocol for a randomised controlled trial.

PubMed

Mitchell, Joanna; Hardeman, Wendy; Pears, Sally; Vasconcelos, Joana C; Prevost, A Toby; Wilson, Ed; Sutton, Stephen

2016-06-27

Physical activity interventions that are targeted at individuals can be effective in encouraging people to be more physically active. However, most such interventions are too long or complex and not scalable to the general population. This trial will test the effectiveness and cost-effectiveness of a very brief physical activity intervention when delivered as part of preventative health checks in primary care (National Health Service (NHS) Health Check). The Very Brief Intervention (VBI) Trial is a two parallel-group, randomised, controlled trial with 1:1 individual allocation and follow-up at 3 months. A total of 1,140 participants will be recruited from 23 primary care practices in the east of England. Participants eligible for an NHS Health Check and who are considered suitable to take part by their doctor and able to provide written informed consent are eligible for the trial. Participants are randomly assigned at the beginning of the NHS Health Check to either 1) the control arm, in which they receive only the NHS Health Check, or 2) the intervention arm, in which they receive the NHS Health Check plus 'Step It Up' (a very brief intervention that can be delivered in 5 minutes by nurses and/or healthcare assistants at the end of the Health Check). 'Step It Up' includes (1) a face-to-face discussion, including feedback on current activity level, recommendations for physical activity, and information on how to use a pedometer, set step goals, and monitor progress; (2) written material supporting the discussion and tips and links to further resources to help increase physical activity; and (3) a pedometer to wear and a step chart for monitoring progress. The primary outcome is accelerometer counts per minute at 3-month follow-up. Secondary outcomes include the time spent in the different levels of physical activity, self-reported physical activity and economic measures. Trial recruitment is underway. The VBI trial will provide evidence on the effectiveness and cost-effectiveness of the Step It Up intervention delivered during NHS Health Checks and will inform policy decisions about introducing very brief interventions into routine primary care practice. ISRCTN Registry, ISRCTN72691150 . Registered on 17 July 2014.

Study protocol for a phase II dose evaluation randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

PubMed

McNally, Dayre; Amrein, Karin; O'Hearn, Katharine; Fergusson, Dean; Geier, Pavel; Henderson, Matt; Khamessan, Ali; Lawson, Margaret L; McIntyre, Lauralyn; Redpath, Stephanie; Weiler, Hope A; Menon, Kusum

2017-01-01

Clinical research has recently demonstrated that vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (PICU) and associated with worse clinical course. Multiple adult ICU trials have suggested that optimization of vitamin D status through high-dose supplementation may reduce mortality and improve other clinically relevant outcomes; however, there have been no trials of rapid normalization in the PICU setting. The objective of this study is to evaluate the safety and efficacy of an enteral weight-based cholecalciferol loading dose regimen in critically ill children with VDD. The VITdAL-PICU pilot study is designed as a multicenter placebo-controlled phase II dose evaluation pilot randomized controlled trial. We aim to randomize 67 VDD critically ill children using a 2:1 randomization schema to receive loading dose enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or a placebo solution. Participants, caregivers and outcome assessors will be blinded to allocation. Eligibility criteria include ICU patient, aged 37 weeks to 18 years, expected ICU length of stay more than 48 h, anticipated access to bloodwork at 7 days, and VDD (blood total 25 hydroxyvitamin D < 50 nmol/L). The primary objective is to determine whether the dosing protocol normalizes vitamin D status, defined as a blood total 25(OH)D concentration above 75 nmol/L. Secondary objectives include an examination of the safety of the dosing regimen (e.g. hypercalcemia, hypercalciuria, nephrocalcinosis), measures of vitamin D axis function (e.g. calcitriol levels, immune function), and protocol feasibility (eligibility criteria, protocol deviations, blinding). Despite significant observational literature suggesting VDD to be a modifiable risk factor in the PICU setting, there is no robust clinical trial evidence evaluating the benefits of rapid normalization. This phase II clinical trial will evaluate an innovative weight-based dosing regimen intended to rapidly and safely normalize vitamin D levels in critically ill children. Study findings will be used to inform the design of a multicenter phase III trial evaluating the clinical and economic benefits to rapid normalization. Recruitment for this trial was initiated in January 2016 and is expected to continue until November 30, 2017. Clinicaltrials.gov NCT02452762.

Calcium supplementation for the prevention of colorectal adenomas: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Bonovas, Stefanos; Fiorino, Gionata; Lytras, Theodore; Malesci, Alberto; Danese, Silvio

2016-05-14

To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas. We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or "high-risk" adenomas), and rated each trial's risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE. Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random-effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence). Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.

Improving chronic disease prevention and screening in primary care: results of the BETTER pragmatic cluster randomized controlled trial.

PubMed

Grunfeld, Eva; Manca, Donna; Moineddin, Rahim; Thorpe, Kevin E; Hoch, Jeffrey S; Campbell-Scherer, Denise; Meaney, Christopher; Rogers, Jess; Beca, Jaclyn; Krueger, Paul; Mamdani, Muhammad

2013-11-20

Primary care provides most of the evidence-based chronic disease prevention and screening services offered by the healthcare system. However, there remains a gap between recommended preventive services and actual practice. This trial (the BETTER Trial) aimed to improve preventive care of heart disease, diabetes, colorectal, breast and cervical cancers, and relevant lifestyle factors through a practice facilitation intervention set in primary care. Pragmatic two-way factorial cluster RCT with Primary Care Physicians' practices as the unit of allocation and individual patients as the unit of analysis. The setting was urban Primary Care Team practices in two Canadian provinces. Eight Primary Care Team practices were randomly assigned to receive the practice-level intervention or wait-list control; 4 physicians in each team (32 physicians) were randomly assigned to receive the patient-level intervention or wait-list control. Patients randomly selected from physicians' rosters were stratified into two groups: 1) general and 2) moderate mental illness. The interventions involved a multifaceted, evidence-based, tailored practice-level intervention with a Practice Facilitator, and a patient-level intervention involving a one-hour visit with a Prevention Practitioner where patients received a tailored 'prevention prescription'. The primary outcome was a composite Summary Quality Index of 28 evidence-based chronic disease prevention and screening actions with pre-defined targets, expressed as the ratio of eligible actions at baseline that were met at follow-up. A cost-effectiveness analysis was conducted. 789 of 1,260 (63%) eligible patients participated. On average, patients were eligible for 8.96 (SD 3.2) actions at baseline. In the adjusted analysis, control patients met 23.1% (95% CI: 19.2% to 27.1%) of target actions, compared to 28.5% (95% CI: 20.9% to 36.0%) receiving the practice-level intervention, 55.6% (95% CI: 49.0% to 62.1%) receiving the patient-level intervention, and 58.9% (95% CI: 54.7% to 63.1%) receiving both practice- and patient-level interventions (patient-level intervention versus control, P < 0.001). The benefit of the patient-level intervention was seen in both strata. The extra cost of the intervention was $26.43CAN (95% CI: $16 to $44) per additional action met. A Prevention Practitioner can improve the implementation of clinically important prevention and screening for chronic diseases in a cost-effective manner.

Causal inference as an emerging statistical approach in neurology: an example for epilepsy in the elderly.

PubMed

Moura, Lidia Mvr; Westover, M Brandon; Kwasnik, David; Cole, Andrew J; Hsu, John

2017-01-01

The elderly population faces an increasing number of cases of chronic neurological conditions, such as epilepsy and Alzheimer's disease. Because the elderly with epilepsy are commonly excluded from randomized controlled clinical trials, there are few rigorous studies to guide clinical practice. When the elderly are eligible for trials, they either rarely participate or frequently have poor adherence to therapy, thus limiting both generalizability and validity. In contrast, large observational data sets are increasingly available, but are susceptible to bias when using common analytic approaches. Recent developments in causal inference-analytic approaches also introduce the possibility of emulating randomized controlled trials to yield valid estimates. We provide a practical example of the application of the principles of causal inference to a large observational data set of patients with epilepsy. This review also provides a framework for comparative-effectiveness research in chronic neurological conditions.

Prophylactic antibiotics or G-CSF for the prevention of infections and improvement of survival in cancer patients undergoing chemotherapy.

PubMed

Herbst, Christine; Naumann, Frauke; Kruse, Eva-Brigitta; Monsef, Ina; Bohlius, Julia; Schulz, Holger; Engert, Andreas

2009-01-21

Febrile neutropenia (FN) and other infectious complications are some of the most serious treatment-related toxicities of chemotherapy for cancer, with a mortality rate of 2% to 21%. The two main types of prophylactic regimens are granulocyte (G-CSF) or granulocyte-macrophage colony stimulating factors (GM-CSF); and antibiotics, frequently quinolones or cotrimoxazole. Important current guidelines recommend the use of colony stimulating factors when the risk of febrile neutropenia is above 20% but they do not mention the use of antibiotics. However, both regimens have been shown to reduce the incidence of infections. Since no systematic review has compared the two regimens, a systematic review was undertaken. To compare the effectiveness of G-CSF or GM-CSF with antibiotics in cancer patients receiving myeloablative chemotherapy with respect to preventing fever, febrile neutropenia, infection, infection-related mortality, early mortality and improving quality of life. We searched The Cochrane Library, MEDLINE, EMBASE, databases of ongoing trials, and conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology (1980 to 2007). We planned to include both full-text and abstract publications. Randomised controlled trials comparing prophylaxis with G-CSF or GM-CSF versus antibiotics in cancer patients of all ages receiving chemotherapy or bone marrow or stem cell transplantation were included for review. Both study arms had to receive identical chemotherapy regimes and other supportive care. Trial eligibility and quality assessment, data extraction and analysis were done in duplicate. Authors were contacted to obtain missing data. We included two eligible randomised controlled trials with 195 patients. Due to differences in the outcomes reported, the trials could not be pooled for meta-analysis. Both trials showed non-significant results favouring antibiotics for the prevention of fever or hospitalisation for febrile neutropenia. There is no evidence for or against antibiotics compared to G(M)-CSFs for the prevention of infections in cancer patients.

Gaining and sustaining schistosomiasis control: study protocol and baseline data prior to different treatment strategies in five African countries.

PubMed

Ezeamama, Amara E; He, Chun-La; Shen, Ye; Yin, Xiao-Ping; Binder, Sue C; Campbell, Carl H; Rathbun, Stephen; Whalen, Christopher C; N'Goran, Eliézer K; Utzinger, Jürg; Olsen, Annette; Magnussen, Pascal; Kinung'hi, Safari; Fenwick, Alan; Phillips, Anna; Ferro, Josefo; Karanja, Diana M S; Mwinzi, Pauline N M; Montgomery, Susan; Secor, W Evan; Hamidou, Amina; Garba, Amadou; King, Charles H; Colley, Daniel G

2016-05-26

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in 2008 to answer strategic questions about schistosomiasis control. For programme managers, a high-priority question is: what are the most cost-effective strategies for delivering preventive chemotherapy (PCT) with praziquantel (PZQ)? This paper describes the process SCORE used to transform this question into a harmonized research protocol, the study design for answering this question, the village eligibility assessments and data resulting from the first year of the study. Beginning in 2009, SCORE held a series of meetings to specify empirical questions and design studies related to different schedules of PCT for schistosomiasis control in communities with high (gaining control studies) and moderate (sustaining control studies) prevalence of Schistosoma infection among school-aged children. Seven studies are currently being implemented in five African countries. During the first year, villages were screened for eligibility, and data were collected on prevalence and intensity of infection prior to randomisation and the implementation of different schemes of PZQ intervention strategies. These studies of different treatment schedules with PZQ will provide the most comprehensive data thus far on the optimal frequency and continuity of PCT for schistosomiasis infection and morbidity control. We expect that the study outcomes will provide data for decision-making for country programme managers and a rich resource of information to the schistosomiasis research community. The trials are registered at International Standard Randomised Controlled Trial registry (identifiers: ISRCTN99401114 , ISRCTN14849830 , ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 and ISRCTN32045736 ).

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

PubMed

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

2015-02-22

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

Prostate cancer - evidence of exercise and nutrition trial (PrEvENT): study protocol for a randomised controlled feasibility trial.

PubMed

Hackshaw-McGeagh, Lucy; Lane, J Athene; Persad, Raj; Gillatt, David; Holly, Jeff M P; Koupparis, Anthony; Rowe, Edward; Johnston, Lyndsey; Cloete, Jenny; Shiridzinomwa, Constance; Abrams, Paul; Penfold, Chris M; Bahl, Amit; Oxley, Jon; Perks, Claire M; Martin, Richard

2016-03-07

A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The 'Prostate Cancer: Evidence of Exercise and Nutrition Trial' investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures. The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation). The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery. Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.

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.

A Randomized, Controlled Trial of Meditation Compared to Exposure Therapy and Education Control on PTSD in Veterans

DTIC Science & Technology

2015-10-01

female; mean age= 48). Three-month posttesting compliance is 82% (136 eligible for 3-month posttesting as of September 30, 2015 with 112 actually... posttested ). Task 6: Delivery of Treatments (on target) Through the end of September, 2015, 157 subjects have been randomized which meets our target...in the Appendices section. The data is presented by treatment arm in a blinded manner. Posttest data is not being analyzed or presented in any form

Interventions to modify sexual risk behaviours for preventing HIV in homeless youth.

PubMed

Naranbhai, Vivek; Abdool Karim, Quarraisha; Meyer-Weitz, Anna

2011-01-19

Homeless youth are at high risk for HIV infection as a consequence of risky sexual behaviour. Interventions for homeless youth are challenging. Assessment of the effectiveness of interventions to modify sexual risk behaviours for preventing HIV in homeless youth is needed. To evaluate and summarize the effectiveness of interventions for modifying sexual risk behaviours and preventing transmission of HIV among homeless youth. We searched electronic databases (CENTRAL, MEDLINE, EMBASE, AIDSearch, Gateway, PsycInfo, LILACS), reference lists of eligible articles, international health agency publication lists, and clinical trial registries. The search was updated January 2010. We contacted authors of published reports and other key role players. Randomised studies of interventions to modify sexual risk behaviour (biological, self-reporting of sexual-risk behaviour or health-seeking behaviour) in homeless youth (12-24 years). Data from eligible studies were extracted by two reviewers. We assessed risk of bias per the Cochrane Collaborations tool. None of the eligible studies reported any primary biological outcomes for this review. Reports of self-reporting sexual risk behaviour outcomes varied across studies precluding calculation of summary measures of effect; we present the outcomes descriptively for each study. We contacted authors for missing or ambiguous data. We identified three eligible studies after screening a total of 255 unique records. All three were performed in the United States of America and recruited substance-abusing male and female adolescents (total N=615) through homeless shelters into randomised controlled trials of independent and non-overlapping behavioural interventions. The three trials differed in theoretical background, delivery method, dosage (number of sessions,) content and outcome assessments. Overall, the variability in delivery and outcomes precluded estimation of summary of effect measures. We assessed the risk of bias to be high for each of the studies. Whilst some effect of the interventions on outcome measures were reported, heterogeneity and lack of robustness in these studies necessitate caution in interpreting the effectiveness of these interventions.  The body of evidence does not permit conclusions on the impact of interventions to modify sexual risk behaviour in homeless youth; more research is required. While the psychosocial and contextual factors that fuel sexual risk behaviours among homeless youth challenge stringent methodologies of RCT's, novel ways for program delivery and trial retention are in need of development. Future trials should comply with rigorous methodology in design, delivery, outcome measurement and reporting.

Effective Strategies to Recruit Young Adults Into the TXT2BFiT mHealth Randomized Controlled Trial for Weight Gain Prevention.

PubMed

Partridge, Stephanie R; Balestracci, Kate; Wong, Annette Ty; Hebden, Lana; McGeechan, Kevin; Denney-Wilson, Elizabeth; Harris, Mark F; Phongsavan, Philayrath; Bauman, Adrian; Allman-Farinelli, Margaret

2015-06-05

Younger adults are difficult to engage in preventive health, yet in Australia they are gaining more weight and increasing in waist circumference faster than middle-to-older adults. A further challenge to engaging 18- to 35-year-olds in interventions is the limited reporting of outcomes of recruitment strategies. This paper describes the outcomes of strategies used to recruit young adults to a randomized controlled trial (RCT), healthy lifestyle mHealth program, TXT2BFiT, for prevention of weight gain. The progression from enquiry through eligibility check to randomization into the trial and the costs of recruitment strategies are reported. Factors associated with nonparticipation are explored. Participants were recruited either via letters of invitation from general practitioners (GPs) or via electronic or print advertisements, including Facebook and Google-social media and advertising-university electronic newsletters, printed posters, mailbox drops, and newspapers. Participants recruited from GP invitation letters had an appointment booked with their GP for eligibility screening. Those recruited from other methods were sent an information pack to seek approval to participate from their own GP. The total number and source of enquiries were categorized according to eligibility and subsequent completion of steps to enrolment. Cost data and details of recruitment strategies were recorded. From 1181 enquiries in total from all strategies, 250 (21.17%) participants were randomized. A total of 5311 invitation letters were sent from 12 GP practices-16 participating GPs. A total of 131 patients enquired with 68 participants randomized (68/74 of those eligible, 92%). The other recruitment methods yielded the remaining 182 randomized participants. Enrolment from print media was 26% of enquiries, from electronic media was 20%, and from other methods was 3%. Across all strategies the average cost of recruitment was Australian Dollar (AUD) $139 per person. The least expensive modality was electronic (AUD $37), largely due to a free feature story on one university Web home page, despite Facebook advertising costing AUD $945 per enrolment. The most expensive was print media at AUD $213 and GP letters at AUD $145 per enrolment. The research indicated that free electronic media was the most cost-effective strategy, with GP letters the least expensive of the paid strategies in comparison to the other strategies. This study is an important contribution for future research into efficacy, translation, and implementation of cost-effective programs for the prevention of weight gain in young adults. Procedural frameworks for recruitment protocols are required, along with systematic reporting of recruitment strategies to reduce unnecessary expenditure and allow for valuable public health prevention programs to go beyond the research setting. Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12612000924853; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362872 (Archived by WebCite at http://www.webcitation.org/6YpNfv1gI).

Surgical and nonsurgical interventions for vulvar and clitoral pain in girls and women living with female genital mutilation: A systematic review.

PubMed

Ezebialu, Ifeanyichukwu; Okafo, Obiamaka; Oringanje, Chukwudi; Ogbonna, Udoezuo; Udoh, Ekong; Odey, Friday; Meremikwu, Martin M

2017-02-01

Vulvar and clitoral pain are known complications of female genital mutilation (FGM). Several interventions have been used to treat these conditions. This review focuses on surgical and nonsurgical interventions to improve vulvar and clitoral pain in women living with FGM. To evaluate the impact of nonsurgical and surgical interventions for alleviating vulvar and clitoral pain in women living with any type of FGM and to assess the associated adverse events. The search included the following major databases: Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov. These were searched from inception until August 10, 2015 without any language restrictions. Study designs included randomized controlled trials, cluster randomized trials, nonrandomized trials, cohort studies, case-control studies, controlled before-and-after studies, historical control studies, and interrupted time series with reported data comparing outcomes among women with FGM who were treated for clitoral or vulvar pain with either surgical or nonsurgical interventions. Two team members independently screened studies for eligibility. No studies were included. Limited information exists on management of vulvar and clitoral pain in women living with FGM. This constitutes an important area for further research. CRD42015024521. © 2017 International Federation of Gynecology and Obstetrics.The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

Evaluation of data completeness in the electronic health record for the purpose of patient recruitment into clinical trials: a retrospective analysis of element presence

PubMed Central

2013-01-01

Background Computerized clinical trial recruitment support is one promising field for the application of routine care data for clinical research. The primary task here is to compare the eligibility criteria defined in trial protocols with patient data contained in the electronic health record (EHR). To avoid the implementation of different patient definitions in multi-site trials, all participating research sites should use similar patient data from the EHR. Knowledge of the EHR data elements which are commonly available from most EHRs is required to be able to define a common set of criteria. The objective of this research is to determine for five tertiary care providers the extent of available data compared with the eligibility criteria of randomly selected clinical trials. Methods Each participating study site selected three clinical trials at random. All eligibility criteria sentences were broken up into independent patient characteristics, which were then assigned to one of the 27 semantic categories for eligibility criteria developed by Luo et al. We report on the fraction of patient characteristics with corresponding structured data elements in the EHR and on the fraction of patients with available data for these elements. The completeness of EHR data for the purpose of patient recruitment is calculated for each semantic group. Results 351 eligibility criteria from 15 clinical trials contained 706 patient characteristics. In average, 55% of these characteristics could be documented in the EHR. Clinical data was available for 64% of all patients, if corresponding data elements were available. The total completeness of EHR data for recruitment purposes is 35%. The best performing semantic groups were ‘age’ (89%), ‘gender’ (89%), ‘addictive behaviour’ (74%), ‘disease, symptom and sign’ (64%) and ‘organ or tissue status’ (61%). No data was available for 6 semantic groups. Conclusions There exists a significant gap in structure and content between data documented during patient care and data required for patient eligibility assessment. Nevertheless, EHR data on age and gender of the patient, as well as selected information on his disease can be complete enough to allow for an effective support of the manual screening process with an intelligent preselection of patients and patient data. PMID:23514203

Assessment of the External Validity of the National Comprehensive Cancer Network and European Society for Medical Oncology Guidelines for Non-Small-Cell Lung Cancer in a Population of Patients Aged 80 Years and Older.

PubMed

Battisti, Nicolò Matteo Luca; Sehovic, Marina; Extermann, Martine

2017-09-01

Non-small-cell lung cancer (NSCLC) is a disease of the elderly, who are under-represented in clinical trials. This challenges the external validity of the evidence base for its management and of current guidelines, that we evaluated in a population of older patients. We retrieved randomized clinical trials (RCTs) supporting the guidelines and identified 18 relevant topics. We matched a cohort of NSCLC patients aged older than 80 years from the Moffitt Cancer Center database with the studies' eligibility criteria to check their qualification for at least 2 studies. Eligibility > 60% was rated full validity, 30% to 60% partial validity, and < 30% limited validity. We obtained data from 760 elderly patients in stage-adjusted groups and collected 244 RCTs from the National Comprehensive Cancer Network (NCCN) and 148 from the European Society for Medical Oncology (ESMO) guidelines. External validity was deemed insufficient for neoadjuvant chemotherapy in stage III disease (27.37% and 25.26% of patients eligible for NCCN and ESMO guidelines, respectively) and use of bevacizumab (13.86% and 16.27% of patients eligible). For ESMO guidelines, it was inadequate regarding double-agent chemotherapy (25.90% of patients eligible), its duration (24.10%) and therapy for Eastern Cooperative Oncology Group performance status 2 patients (17.74%). For NCCN guidelines external validity was lacking for neoadjuvant chemoradiotherapy in stage IIIA disease (25.86% of patients eligible). Our analysis highlighted the effect of RCT eligibility criteria on guidelines' external validity in elderly patients. Eligibility criteria should be carefully considered in trial design and more studies that do not exclude elderly patients should be included in guidelines. Copyright © 2017 Elsevier Inc. All rights reserved.

Randomised trials comparing different healthcare settings: an exploratory review of the impact of pre-trial preferences on participation, and discussion of other methodological challenges.

PubMed

Corbett, Mark S; Watson, Judith; Eastwood, Alison

2016-10-19

We recently published a systematic review of different healthcare settings (such as outpatient, community or home) for administering intravenous chemotherapy, and concluded that performing conventionally designed randomised trials was difficult. The main problems were achieving adequate trial accrual rates and recruiting a study population which adequately represented the target population of interest. These issues stemmed from the fact that potential participants may have had pre-trial perceptions about the trial settings they may be allocated; such preferences will sometimes be strong enough for patients to decline an invitation to participate in a trial. A patient preference trial design (in which patients can choose, or be randomised to, an intervention) may have obviated these recruitment issues, although none of the trials used such a design. In order to gain a better understanding of the broader prevalence and extent of these preference issues (and any other methodological challenges), we undertook an exploratory review of settings trials in any area of healthcare treatment research. We searched The Cochrane Library and Google Scholar and used snowballing methods to identify trials comparing different healthcare settings. Trial accrual was affected by patient preferences for a setting in 15 of the 16 identified studies; birth setting trials were the most markedly affected, with between 68 % and 85 % of eligible women declining to participate specifically because of preference for a particular healthcare setting. Recruitment into substance abuse and chemotherapy setting studies was also notably affected by preferences. Only four trials used a preference design: the proportion of eligible patients choosing to participate via a preference group ranged from between 33 % and 67 %. In trials of healthcare settings, accrual may be seriously affected by patient preferences. The use of trial designs which incorporate a preference component should therefore strongly be considered. When designing such trials, investigators should consider settings to be complex interventions, which are likely to have linked components which may be difficult to control for. Careful thought is also needed regarding the choice of comparator settings and the most appropriate outcome measures to be used.

Can a documentary increase help-seeking intentions in men? A randomised controlled trial.

PubMed

King, Kylie Elizabeth; Schlichthorst, Marisa; Spittal, Matthew J; Phelps, Andrea; Pirkis, Jane

2018-01-01

We investigated whether a public health intervention-a three-part documentary called Man Up which explored the relationship between masculinity and mental health, well-being and suicidality-could increase men's intentions to seek help for personal and emotional problems. We recruited men aged 18 years or over who were not at risk of suicide to participate in a double-blind randomised controlled trial. Participants were randomly assigned (1:1) via computer randomisation to view Man Up (the intervention) or a control documentary. We hypothesised that 4 weeks after viewing Man Up participants would report higher levels of intention to seek help than those who viewed the control documentary. Our primary outcome was assessed using the General Help Seeking Questionnaire, and was analysed for all participants. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616001169437, Universal Trial Number: U1111-1186-1459) and was funded by the Movember Foundation. Three hundred and fifty-four men were assessed for eligibility for the trial and randomised to view Man Up or the control documentary. Of these, 337 completed all stages (nine participants were lost to follow-up in the intervention group and eight in the control group). Linear regression analysis showed a significant increase in intentions to seek help in the intervention group, but not in the control group (coef.=2.06, 95% CI 0.48 to 3.63, P=0.01). Our trial demonstrates the potential for men's health outcomes to be positively impacted by novel, media-based public health interventions that focus on traditional masculinity. ACTRN12616001169437, Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Effectiveness of Endoscopic Gastroplasty for Obesity Treatment According to FDA Thresholds: Systematic Review and Meta-Analysis Based on Randomized Controlled Trials.

PubMed

Madruga-Neto, Antonio Coutinho; Bernardo, Wanderley Marques; de Moura, Diogo Turiani Hourneaux; Brunaldi, Vitor Ottoboni; Martins, Rafael Krieger; Josino, Iatagan Rocha; de Moura, Eduardo Turiani Hourneaux; de Souza, Thiago Ferreira; Santo, Marco Aurélio; de Moura, Eduardo Guimarães Hourneaux

2018-06-16

Endoscopic bariatric therapies (EBTs) are promising alternatives to conventional surgery for obesity. The aim of this study is to compare efficacy and safety through a systematic review and meta-analysis of the endoscopic gastroplasty techniques versus conservative treatment. We searched MEDLINE, EMBASE, Cochrane CENTRAL, Lilacs/Bireme. Randomized controlled trials (RCTs) enrolling obese patients comparing endoscopic gastroplasty to sham or diet/exercise were considered eligible. Among 6014 records, three RCTs were selected for meta-analysis. The total sample was 459 patients (312 EBTs vs 147 control). Mean total body weight loss in the intervention group (IG) was 4.8% higher than the control group (CG) at 12 months (p = 0.01). The IG responder rate was 44.31% at 12 months. Therefore, the endoscopic gastroplasty is more effective than conservative therapies but do not achieve FDA thresholds.

The value of structured data elements from electronic health records for identifying subjects for primary care clinical trials.

PubMed

Ateya, Mohammad B; Delaney, Brendan C; Speedie, Stuart M

2016-01-11

An increasing number of clinical trials are conducted in primary care settings. Making better use of existing data in the electronic health records to identify eligible subjects can improve efficiency of such studies. Our study aims to quantify the proportion of eligibility criteria that can be addressed with data in electronic health records and to compare the content of eligibility criteria in primary care with previous work. Eligibility criteria were extracted from primary care studies downloaded from the UK Clinical Research Network Study Portfolio. Criteria were broken into elemental statements. Two expert independent raters classified each statement based on whether or not structured data items in the electronic health record can be used to determine if the statement was true for a specific patient. Disagreements in classification were discussed until 100 % agreement was reached. Statements were also classified based on content and the percentages of each category were compared to two similar studies reported in the literature. Eligibility criteria were retrieved from 228 studies and decomposed into 2619 criteria elemental statements. 74 % of the criteria elemental statements were considered likely associated with structured data in an electronic health record. 79 % of the studies had at least 60 % of their criteria statements addressable with structured data likely to be present in an electronic health record. Based on clinical content, most frequent categories were: "disease, symptom, and sign", "therapy or surgery", and "medication" (36 %, 13 %, and 10 % of total criteria statements respectively). We also identified new criteria categories related to provider and caregiver attributes (2.6 % and 1 % of total criteria statements respectively). Electronic health records readily contain much of the data needed to assess patients' eligibility for clinical trials enrollment. Eligibility criteria content categories identified by our study can be incorporated as data elements in electronic health records to facilitate their integration with clinical trial management systems.

A systematic review and meta-analysis of trials of social network interventions in type 2 diabetes.

PubMed

Spencer-Bonilla, Gabriela; Ponce, Oscar J; Rodriguez-Gutierrez, Rene; Alvarez-Villalobos, Neri; Erwin, Patricia J; Larrea-Mantilla, Laura; Rogers, Anne; Montori, Victor M

2017-08-21

In the care of patients with type 2 diabetes, self-management is emphasised and studied while theory and observations suggest that patients also benefit from social support. We sought to assess the effect of social network interventions on social support, glycaemic control and quality of life in patients with type 2 diabetes. We searched Ovid MEDLINE, Ovid EBM Reviews, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO and CINAHL through April 2017 for randomised clinical trials (RCTs) of social network interventions in patients with type 2 diabetes. Reviewers working independently and in duplicate assessed eligibility and risk of bias, and extracted data from eligible RCTs. We pooled estimates using inverse variance random effects meta-analysis. We found 19 eligible RCTs enrolling 2319 participants. Social network interventions were commonly based on individual behaviour change rather than social or interpersonal theories of self-management, were educational, and sought to engage social network members for their knowledge and experience. Interventions improved social support (0.74 SD (95% CI 0.32 to 1.15), I 2 =89%, 8 RCTs) and haemoglobin A1c at 3 months (-0.25 percentage points (95% CI -0.40 to -0.11), I 2 =12%, 9 RCTs), but not quality of life. Despite a compelling theoretical base, researchers have only minimally studied the value of interventions targeting patients' social networks on diabetes care. Although the body of evidence to date is limited, and based on individual behaviour change theories, the results are promising. This review challenges the scientific community to design and test theory-based interventions that go beyond self-management approaches to focus on the largely untapped potential of social networks to improve diabetes care. CRD42016036117. © 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.

Comparative effectiveness of different wound dressings for patients with partial-thickness burns: study protocol of a systematic review and a Bayesian framework network meta-analysis

PubMed Central

Jiang, Qiong; Chen, Zhao-Hong; Wang, Shun-Bin; Chen, Xiao-Dong

2017-01-01

Introduction Selecting a suitable wound dressing for patients with partial-thickness burns (PTBs) is important in wound care. However, the comparative effectiveness of different dressings has not been studied. We report the protocol of a network meta-analysis designed to combine direct and indirect evidence of wound dressings in the management of PTB. Methods and analysis We will search for randomised controlled trials (RCTs) evaluating the wound-healing effect of a wound dressing in the management of PTB. Searches will be conducted in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Wounds Group Specialised Register and CINAHL. A comprehensive search strategy is developed to retrieve articles reporting potentially eligible RCTs. Besides, we will contact the experts in the field and review the conference proceedings to locate non-published studies. The reference lists of articles will be reviewed for any candidate studies. Two independent reviewers will screen titles and abstracts of the candidate articles. All eligible RCTs will be obtained in full text to perform a review. Disagreement on eligibility of an RCT will be solved by group discussion. The information of participants, interventions, comparisons and outcomes from included RCTs will be recorded and summarised. The primary outcome is time to complete wound healing. Secondary outcomes include the proportion of burns completely healed at the end of treatment, change in wound surface area at the end of treatment, incidence of adverse events, etc. Ethics and dissemination The result of this review will provide evidence for the comparative effectiveness of different wound dressings in the management of PTB. It will also facilitate decision-making in choosing a suitable wound dressing. We will disseminate the review through a peer-review journal and conference abstracts or posters. Trial registration number PROSPERO CRD42016041574; Pre-results. PMID:28336737

Effects of the Informed Health Choices primary school intervention on the ability of children in Uganda to assess the reliability of claims about treatment effects: a cluster-randomised controlled trial.

PubMed

Nsangi, Allen; Semakula, Daniel; Oxman, Andrew D; Austvoll-Dahlgren, Astrid; Oxman, Matt; Rosenbaum, Sarah; Morelli, Angela; Glenton, Claire; Lewin, Simon; Kaseje, Margaret; Chalmers, Iain; Fretheim, Atle; Ding, Yunpeng; Sewankambo, Nelson K

2017-07-22

Claims about what improves or harms our health are ubiquitous. People need to be able to assess the reliability of these claims. We aimed to evaluate an intervention designed to teach primary school children to assess claims about the effects of treatments (ie, any action intended to maintain or improve health). In this cluster-randomised controlled trial, we included primary schools in the central region of Uganda that taught year-5 children (aged 10-12 years). We excluded international schools, special needs schools for children with auditory and visual impairments, schools that had participated in user-testing and piloting of the resources, infant and nursery schools, adult education schools, and schools that were difficult for us to access in terms of travel time. We randomly allocated a representative sample of eligible schools to either an intervention or control group. Intervention schools received the Informed Health Choices primary school resources (textbooks, exercise books, and a teachers' guide). Teachers attended a 2 day introductory workshop and gave nine 80 min lessons during one school term. The lessons addressed 12 concepts essential to assessing claims about treatment effects and making informed health choices. We did not intervene in the control schools. The primary outcome, measured at the end of the school term, was the mean score on a test with two multiple-choice questions for each of the 12 concepts and the proportion of children with passing scores on the same test. This trial is registered with the Pan African Clinical Trial Registry, number PACTR201606001679337. Between April 11, 2016, and June 8, 2016, 2960 schools were assessed for eligibility; 2029 were eligible, and a random sample of 170 were invited to recruitment meetings. After recruitment meetings, 120 eligible schools consented and were randomly assigned to either the intervention group (n=60, 76 teachers and 6383 children) or control group (n=60, 67 teachers and 4430 children). The mean score in the multiple-choice test for the intervention schools was 62·4% (SD 18·8) compared with 43·1% (15·2) for the control schools (adjusted mean difference 20·0%, 95% CI 17·3-22·7; p<0·00001). In the intervention schools, 3967 (69%) of 5753 children achieved a predetermined passing score (≥13 of 24 correct answers) compared with 1186 (27%) of 4430 children in the control schools (adjusted difference 50%, 95% CI 44-55). The intervention was effective for children with different levels of reading skills, but was more effective for children with better reading skills. The use of the Informed Health Choices primary school learning resources, after an introductory workshop for the teachers, led to a large improvement in the ability of children to assess claims about the effects of treatments. The results show that it is possible to teach primary school children to think critically in schools with large student to teacher ratios and few resources. Future studies should address how to scale up use of the resources, long-term effects, including effects on actual health choices, transferability to other countries, and how to build on this programme with additional primary and secondary school learning resources. Research Council of Norway. Copyright © 2017 Elsevier Ltd. All rights reserved.

Wordless intervention for epilepsy in learning disabilities (WIELD): study protocol for a randomized controlled feasibility trial.

PubMed

Durand, Marie-Anne; Gates, Bob; Parkes, Georgina; Zia, Asif; Friedli, Karin; Barton, Garry; Ring, Howard; Oostendorp, Linda; Wellsted, David

2014-11-20

Epilepsy is the most common neurological problem that affects people with learning disabilities. The high seizure frequency, resistance to treatments, associated skills deficit and co-morbidities make the management of epilepsy particularly challenging for people with learning disabilities. The Books Beyond Words booklet for epilepsy uses images to help people with learning disabilities manage their condition and improve quality of life. Our aim is to conduct a randomized controlled feasibility trial exploring key methodological, design and acceptability issues, in order to subsequently undertake a large-scale randomized controlled trial of the Books Beyond Words booklet for epilepsy. We will use a two-arm, single-centre randomized controlled feasibility design, over a 20-month period, across five epilepsy clinics in Hertfordshire, United Kingdom. We will recruit 40 eligible adults with learning disabilities and a confirmed diagnosis of epilepsy and will randomize them to use either the Books Beyond Words booklet plus usual care (intervention group) or to receive routine information and services (control group). We will collect quantitative data about the number of eligible participants, number of recruited participants, demographic data, discontinuation rates, variability of the primary outcome measure (quality of life: Epilepsy and Learning Disabilities Quality of Life scale), seizure severity, seizure control, intervention's patterns of use, use of other epilepsy-related information, resource use and the EQ-5D-5L health questionnaire. We will also gather qualitative data about the feasibility and acceptability of the study procedures and the Books Beyond Words booklet. Ethical approval for this study was granted on 28 April 2014, by the Wales Research Ethics Committee 5. Recruitment began on 1 July 2014. The outcomes of this feasibility study will be used to inform the design and methodology of a definitive study, adequately powered to determine the impact of the Books Beyond Words intervention to improve the management of epilepsy in people with learning disabilities. http://ISRCTN80067039 (Date of ISRCTN assignation: 23 April 2014).

The feasibility of a randomized controlled trial of esophagectomy for esophageal cancer - the ROMIO (Randomized Oesophagectomy: Minimally Invasive or Open) study: protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background There is a need for evidence of the clinical effectiveness of minimally invasive surgery for the treatment of esophageal cancer, but randomized controlled trials in surgery are often difficult to conduct. The ROMIO (Randomized Open or Minimally Invasive Oesophagectomy) study will establish the feasibility of a main trial which will examine the clinical and cost-effectiveness of minimally invasive and open surgical procedures for the treatment of esophageal cancer. Methods/Design A pilot randomized controlled trial (RCT), in two centers (University Hospitals Bristol NHS Foundation Trust and Plymouth Hospitals NHS Trust) will examine numbers of incident and eligible patients who consent to participate in the ROMIO study. Interventions will include esophagectomy by: (1) open gastric mobilization and right thoracotomy, (2) laparoscopic gastric mobilization and right thoracotomy, and (3) totally minimally invasive surgery (in the Bristol center only). The primary outcomes of the feasibility study will be measures of recruitment, successful development of methods to monitor quality of surgery and fidelity to a surgical protocol, and development of a core outcome set to evaluate esophageal cancer surgery. The study will test patient-reported outcomes measures to assess recovery, methods to blind participants, assessments of surgical morbidity, and methods to capture cost and resource use. ROMIO will integrate methods to monitor and improve recruitment using audio recordings of consultations between recruiting surgeons, nurses, and patients to provide feedback for recruiting staff. Discussion The ROMIO study aims to establish efficient methods to undertake a main trial of minimally invasive surgery versus open surgery for esophageal cancer. Trial registration The pilot trial has Current Controlled Trials registration number ISRCTN59036820(25/02/2013) at http://www.controlled-trials.com; the ROMIO trial record at that site gives a link to the original version of the study protocol. PMID:24888266

Smoking characteristics and comorbidities in the power to quit randomized clinical trial for homeless smokers.

PubMed

Okuyemi, Kolawole S; Goldade, Kate; Whembolua, Guy-Lucien; Thomas, Janet L; Eischen, Sara; Guo, Hongfei; Connett, John E; Grant, Jon; Ahluwalia, Jasjit S; Resnicow, Ken; Owen, Greg; Gelberg, Lillian; Jarlais, Don Des

2013-01-01

Smoking prevalence in homeless populations is strikingly high (∼70%); yet, little is known about effective smoking cessation interventions for this population. We conducted a community-based clinical trial, Power To Quit (PTQ), to assess the effects of motivational interviewing (MI) and nicotine patch (nicotine replacement therapy [NRT]) on smoking cessation among homeless smokers. This paper describes the smoking characteristics and comorbidities of smokers in the study. Four hundred and thirty homeless adult smokers were randomized to either the intervention arm (NRT + MI) or the control arm (NRT + Brief Advice). Baseline assessment included demographic information, shelter status, smoking history, motivation to quit smoking, alcohol/other substance abuse, and psychiatric comorbidities. Of the 849 individuals who completed the eligibility survey, 578 (68.1%) were eligible and 430 (74.4% of eligibles) were enrolled. Participants were predominantly Black, male, and had mean age of 44.4 years (S D = 9.9), and the majority were unemployed (90.5%). Most participants reported sleeping in emergency shelters; nearly half had been homeless for more than a year. Nearly all the participants were daily smokers who smoked an average of 20 cigarettes/day. Nearly 40% had patient health questionnaire-9 depression scores in the moderate or worse range, and more than 80% screened positive for lifetime history of drug abuse or dependence. This study demonstrates the feasibility of enrolling a diverse sample of homeless smokers into a smoking cessation clinical trial. The uniqueness of the study sample enables investigators to examine the influence of nicotine dependence as well as psychiatric and substance abuse comorbidities on smoking cessation outcomes.

Computerized patient identification for the EMBRACA clinical trial using real-time data from the PRAEGNANT network for metastatic breast cancer patients.

PubMed

Hein, Alexander; Gass, Paul; Walter, Christina Barbara; Taran, Florin-Andrei; Hartkopf, Andreas; Overkamp, Friedrich; Kolberg, Hans-Christian; Hadji, Peyman; Tesch, Hans; Ettl, Johannes; Wuerstlein, Rachel; Lounsbury, Debra; Lux, Michael P; Lüftner, Diana; Wallwiener, Markus; Müller, Volkmar; Belleville, Erik; Janni, Wolfgang; Fehm, Tanja N; Wallwiener, Diethelm; Ganslandt, Thomas; Ruebner, Matthias; Beckmann, Matthias W; Schneeweiss, Andreas; Fasching, Peter A; Brucker, Sara Y

2016-07-01

As breast cancer is a diverse disease, clinical trials are becoming increasingly diversified and are consequently being conducted in very small subgroups of patients, making study recruitment increasingly difficult. The aim of this study was to assess the use of data from a remote data entry system that serves a large national registry for metastatic breast cancer. The PRAEGNANT network is a real-time registry with an integrated biomaterials bank that was designed as a scientific study and as a means of identifying patients who are eligible for clinical trials, based on clinical and molecular information. Here, we report on the automated use of the clinical data documented to identify patients for a clinical trial (EMBRACA) for patients with metastatic breast cancer. The patients' charts were assessed by two independent physicians involved in the clinical trial and also by a computer program that tested patients for eligibility using a structured query language script. In all, 326 patients from two study sites in the PRAEGNANT network were included in the analysis. Using expert assessment, 120 of the 326 patients (37 %) appeared to be eligible for inclusion in the EMBRACA study; with the computer algorithm assessment, a total of 129 appeared to be eligible. The sensitivity of the computer algorithm was 0.87 and its specificity was 0.88. Using computer-based identification of patients for clinical trials appears feasible. With the instrument's high specificity, its application in a large cohort of patients appears to be feasible, and the workload for reassessing the patients is limited.

Neoadjuvant chemotherapy regimens in treatment of breast cancer: a systematic review and network meta-analysis protocol.

PubMed

Pathak, Mona; Dwivedi, Sada Nand; Deo, S V S; Thakur, Bhaskar; Sreenivas, Vishnubhatla; Rath, G K

2018-06-26

Neoadjuvant chemotherapy (NACT), a standard of care for locally advanced breast cancer patients, is widely used for early breast cancer patients also. The varying role of regimens used as NACT needs to be investigated. Despite availability of some randomized controlled trials (RCTs), it is unclear which treatment regimen suits best. Further, there is no study comparing all the three regimens. Accordingly, present study will compare the efficacy of anthracyclines, taxanes, and targeted therapy administered in neoadjuvant setting on the basis of oncological outcomes and functional outcomes. Online databases PubMed and Cochrane Register of Controlled Trials will be searched to acquire eligible studies. Further, content of relevant journals, references of relevant articles, and proceedings of major related conference will also be searched. The RCTs comparing any of abovementioned regimen as NACT on breast cancer patients will be eligible. Two reviewers independently and in duplicate will screen the records on the basis of title and abstract and complete full-text review to determine eligibility. Similarly, data extraction and risk of bias assessment will be done by two independent reviewers. The pair-wise meta-analysis as well as network meta-analysis will be conducted to assess the relative efficacy of anthracyclines, taxanes, and targeted therapy regimens. The present systematic review will improve the understanding of the relative efficacies of the three treatment regimens and possibly guide the clinical practices by providing the current best evidence on the efficacy of various regimens of NACT in the management of breast cancer patients. PROSPERO ( CRD42016027236 ).

Development of a Novel Six-Month Nutrition Intervention for a Randomized Trial in Older Men with Mobility Limitations.

PubMed

Apovian, C M; Singer, M R; Campbell, W W; Bhasin, S; McCarthy, A C; Shah, M; Basaria, S; Moore, L L

2017-01-01

Nutrition impacts the development of sarcopenia and protein intake is an important modulator of skeletal muscle mass loss in older people. The Optimizing Protein Intake in Older Men with Mobility Limitation (OPTIMEN) Trial was designed to assess the independent and combined effects of higher protein intake and a promyogenic agent, testosterone, on lean body mass, muscle strength and physical function in older men with mobility disability. The purpose of this paper is to describe the experimental design and nutrition intervention, including techniques used by research dietitians to develop and deliver energy and protein-specific meals to the homes of community-dwelling participants. Strategies to enhance long-term dietary compliance are detailed. Randomized, double-blind, placebo-controlled six-month intervention trial. Participants were recruited from Boston MA USA and surrounding communities. Older men who were mobility-limited (Short Physical Performance Battery (SPPB) 3-10) and consuming less protein (<0.83 g/kg/day) were recruited for this study. Here we report the successful implementation of a double-blind, placebo-controlled, parallel group, randomized controlled trial with a 6-month intervention period among community-living men, age 65 years and older with a mobility limitation. A controlled feeding plan was used to deliver required energy intakes and prescribed protein quantities of 0.8 or 1.3 grams/kilogram/day (g/kg/d) in three meals plus snacks and supplements. A 2x2 factorial design was used to assess the effects of protein level alone and in combination with testosterone (vs. placebo) on changes in lean body mass (primary outcome), muscle strength, and physical function. A total of 154 men met the eligibility criteria; 112 completed a 2-week run-in period designed to evaluate compliance with the nutrition intervention. Of these, 92 subjects met compliance eligibility criteria and agreed to be randomized; 85% completed the full trial. The study successfully delivered three meals per day to subjects, with a high degree of compliance and subject satisfaction. Overall self-reported compliance rates were 80% and 93% for the meals and supplements, respectively. Details of compliance strategies are discussed. This community-based study design may serve as a model for longer-term nutritional interventions requiring monitoring of dietary compliance in a home-based feeding and supplementation trial.

Home-based interventions for black patients with uncontrolled hypertension: a cluster randomized controlled trial

PubMed Central

Feldman, Penny H; McDonald, Margaret V; Barrón, Yolanda; Gerber, Linda M; Peng, Timothy R

2016-01-01

Aim: Assess the comparative effectiveness of two blood pressure (BP) control interventions for black patients with uncontrolled hypertension. Patients & methods: A total of 845 patients were enrolled in a three-arm cluster randomized trial. On admission of an eligible patient, field nurses were randomized to usual care, a basic or augmented intervention. Results: Across study arms there were no significant 12 months differences in BP control rates (primary outcome) (25% usual care, 26% basic intervention, 22% augmented intervention); systolic BP (143.8 millimeters of mercury [mmHg], 146.9 mmHG, 143.9 mmHG, respectively); medication intensification (47, 43, 54%, respectively); or self-management score (18.7, 18.7, 17.9, respectively). Adjusted systolic BP dropped more than 10 mmHg from baseline to 12 months (155.5–145.4 mmHg) among all study participants. Conclusion: Neither the augmented nor basic intervention was more effective than usual care in improving BP control, systolic BP, medication intensification or patient self-management. Usual home care yielded substantial improvements, creating a high comparative effectiveness threshold. Clinical Trial Registration: NCT00139490. PMID:26946952

The Effectiveness of Music in Pediatric Healthcare: A Systematic Review of Randomized Controlled Trials

PubMed Central

Treurnicht Naylor, Karline; Kingsnorth, Shauna; Lamont, Andrea; McKeever, Patricia; Macarthur, Colin

2011-01-01

The aim of this study was to systematically review the effectiveness of music on pediatric health-related outcomes. Five electronic databases were searched for randomized controlled/crossover trial designs published between 1984 and 2009. Eligible studies used music as a therapy or intervention, included participants 1 to 18 years, and focused on at least one health-related outcome (with the exclusion of procedural pain). Seventeen studies met the inclusion criteria. Quantitative synthesis was hampered by an inability to aggregate data arising from heterogeneity of interventions, outcomes and measurement tools. Qualitative synthesis revealed significant improvements in one or more health outcomes within four of seven trials involving children with learning and developmental disorders; two of three trials involving children experiencing stressful life events; and four of five trials involving children with acute and/or chronic physical illness. No significant effects were found for two trials involving children with mood disorders and related psychopathology. These findings offer limited qualitative evidence to support the effectiveness of music on health-related outcomes for children and adolescents with clinical diagnoses. Recommendations for establishing a consensus on research priorities and addressing methodological limitations are put forth to support the continued advancement of this popular intervention. PMID:20976017

Comprehensive, Individualized, Person-Centered Management of Community-Residing Persons with Moderate-to-Severe Alzheimer Disease: A Randomized Controlled Trial.

PubMed

Reisberg, Barry; Shao, Yongzhao; Golomb, James; Monteiro, Isabel; Torossian, Carol; Boksay, Istvan; Shulman, Melanie; Heller, Sloane; Zhu, Zhaoyin; Atif, Ayesha; Sidhu, Jaskirat; Vedvyas, Alok; Kenowsky, Sunnie

2017-01-01

The aim was to examine added benefits of a Comprehensive, Individualized, Person-Centered Management (CI-PCM) program to memantine treatment. This was a 28-week, clinician-blinded, randomized, controlled, parallel-group study, with a similar study population, similar eligibility criteria, and a similar design to the memantine pivotal trial of Reisberg et al. [N Engl J Med 2003;348:1333-1341]. Twenty eligible community-residing Alzheimer disease (AD) subject-caregiver dyads were randomized to the CI-PCM program (n = 10) or to usual community care (n = 10). Primary outcomes were the New York University Clinician's Interview-Based Impression of Change Plus Caregiver Input (NYU-CIBIC-Plus), assessed by one clinician set, and an activities of daily living inventory, assessed by a separate clinician set at baseline and at weeks 4, 12, and 28. Primary outcomes showed significant benefits of the CI-PCM program at all post-baseline evaluations. Improvement on the NYU-CIBIC-Plus in the management group at 28 weeks was 2.9 points over the comparator group. The memantine 2003 trial showed an improvement of 0.3 points on this global measure in memantine-treated versus placebo-randomized subjects at 28 weeks. Hence, globally, the management program intervention benefits were 967% greater than memantine treatment alone. These results are approximately 10 times those usually observed with both nonpharmacological and pharmacological treatments and indicate substantial benefits with the management program for advanced AD persons. © 2017 S. Karger AG, Basel.

Does audiovisual distraction reduce dental anxiety in children under local anesthesia? A systematic review and meta-analysis.

PubMed

Zhang, Cai; Qin, Dan; Shen, Lu; Ji, Ping; Wang, Jinhua

2018-03-02

To perform a systematic review and meta-analysis on the effects of audiovisual distraction on reducing dental anxiety in children during dental treatment under local anesthesia. The authors identified eligible reports published through August 2017 by searching PubMed, EMBASE, and Cochrane Central Register of Controlled Trials. Clinical trials that reported the effects of audiovisual distraction on children's physiological measures, self-reports and behavior rating scales during dental treatment met the minimum inclusion requirements. The authors extracted data and performed a meta-analysis of appropriate articles. Nine eligible trials were included and qualitatively analyzed; some of these trials were also quantitatively analyzed. Among the physiological measures, heart rate or pulse rate was significantly lower (p=0.01) in children subjected to audiovisual distraction during dental treatment under local anesthesia than in those who were not; a significant difference in oxygen saturation was not observed. The majority of the studies using self-reports and behavior rating scales suggested that audiovisual distraction was beneficial in reducing anxiety perception and improving children's cooperation during dental treatment. The audiovisual distraction approach effectively reduces dental anxiety among children. Therefore, we suggest the use of audiovisual distraction when children need dental treatment under local anesthesia. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Non-invasive versus invasive management in patients with prior coronary artery bypass surgery with a non-ST segment elevation acute coronary syndrome: study design of the pilot randomised controlled trial and registry (CABG-ACS)

PubMed Central

Lee, Matthew M Y; Petrie, Mark C; Rocchiccioli, Paul; Simpson, Joanne; Jackson, Colette; Brown, Ammani; Corcoran, David; Mangion, Kenneth; McEntegart, Margaret; Shaukat, Aadil; Rae, Alan; Hood, Stuart; Peat, Eileen; Findlay, Iain; Murphy, Clare; Cormack, Alistair; Bukov, Nikolay; Balachandran, Kanarath; Papworth, Richard; Ford, Ian; Briggs, Andrew; Berry, Colin

2016-01-01

Introduction There is an evidence gap about how to best treat patients with prior coronary artery bypass grafts (CABGs) presenting with non-ST segment elevation acute coronary syndromes (NSTE-ACS) because historically, these patients were excluded from pivotal randomised trials. We aim to undertake a pilot trial of routine non-invasive management versus routine invasive management in patients with NSTE-ACS with prior CABG and optimal medical therapy during routine clinical care. Our trial is a proof-of-concept study for feasibility, safety, potential efficacy and health economic modelling. We hypothesise that a routine invasive approach in patients with NSTE-ACS with prior CABG is not superior to a non-invasive approach with optimal medical therapy. Methods and analysis 60 patients will be enrolled in a randomised clinical trial in 4 hospitals. A screening log will be prospectively completed. Patients not randomised due to lack of eligibility criteria and/or patient or physician preference and who give consent will be included in a registry. We will gather information about screening, enrolment, eligibility, randomisation, patient characteristics and adverse events (including post-discharge). The primary efficacy outcome is the composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction and hospitalisation for heart failure. The primary safety outcome is the composite of bleeding, stroke, procedure-related myocardial infarction and worsening renal function. Health status will be assessed using EuroQol 5 Dimensions (EQ-5D) assessed at baseline and 6 monthly intervals, for at least 18 months. Trial registration number NCT01895751 (ClinicalTrials.gov). PMID:27110377

Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials123

PubMed Central

Juraschek, Stephen P; Guallar, Eliseo; Appel, Lawrence J

2012-01-01

Background: In observational studies, increased vitamin C intake, vitamin C supplementation, and higher blood concentrations of vitamin C are associated with lower blood pressure (BP). However, evidence for blood pressure–lowering effects of vitamin C in clinical trials is inconsistent. Objective: The objective was to conduct a systematic review and meta-analysis of clinical trials that examined the effects of vitamin C supplementation on BP. Design: We searched Medline, EMBASE, and Central databases from 1966 to 2011. Prespecified inclusion criteria were as follows: 1) use of a randomized controlled trial design; 2) trial reported effects on systolic BP (SBP) or diastolic BP (DBP) or both; 3) trial used oral vitamin C and concurrent control groups; and 4) trial had a minimum duration of 2 wk. BP effects were pooled by random-effects models, with trials weighted by inverse variance. Results: Twenty-nine trials met eligibility criteria for the primary analysis. The median dose was 500 mg/d, the median duration was 8 wk, and trial sizes ranged from 10 to 120 participants. The pooled changes in SBP and DBP were −3.84 mm Hg (95% CI: −5.29, −2.38 mm Hg; P < 0.01) and −1.48 mm Hg (95% CI: −2.86, −0.10 mm Hg; P = 0.04), respectively. In trials in hypertensive participants, corresponding reductions in SBP and DBP were −4.85 mm Hg (P < 0.01) and −1.67 mm Hg (P = 0.17). After the inclusion of 9 trials with imputed BP effects, BP effects were attenuated but remained significant. Conclusions: In short-term trials, vitamin C supplementation reduced SBP and DBP. Long-term trials on the effects of vitamin C supplementation on BP and clinical events are needed. PMID:22492364

The Data Gap in the EHR for Clinical Research Eligibility Screening.

PubMed

Butler, Alex; Wei, Wei; Yuan, Chi; Kang, Tian; Si, Yuqi; Weng, Chunhua

2018-01-01

Much effort has been devoted to leverage EHR data for matching patients into clinical trials. However, EHRs may not contain all important data elements for clinical research eligibility screening. To better design research-friendly EHRs, an important step is to identify data elements frequently used for eligibility screening but not yet available in EHRs. This study fills this knowledge gap. Using the Alzheimer's disease domain as an example, we performed text mining on the eligibility criteria text in Clinicaltrials.gov to identify frequently used eligibility criteria concepts. We compared them to the EHR data elements of a cohort of Alzheimer's Disease patients to assess the data gap by usingthe OMOP Common Data Model to standardize the representations for both criteria concepts and EHR data elements. We identified the most common SNOMED CT concepts used in Alzheimer 's Disease trials, andfound 40% of common eligibility criteria concepts were not even defined in the concept space in the EHR dataset for a cohort of Alzheimer 'sDisease patients, indicating a significant data gap may impede EHR-based eligibility screening. The results of this study can be useful for designing targeted research data collection forms to help fill the data gap in the EHR.

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.

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.

Trial Prospector: Matching Patients with Cancer Research Studies Using an Automated and Scalable Approach

PubMed Central

Sahoo, Satya S; Tao, Shiqiang; Parchman, Andrew; Luo, Zhihui; Cui, Licong; Mergler, Patrick; Lanese, Robert; Barnholtz-Sloan, Jill S; Meropol, Neal J; Zhang, Guo-Qiang

2014-01-01

Cancer is responsible for approximately 7.6 million deaths per year worldwide. A 2012 survey in the United Kingdom found dramatic improvement in survival rates for childhood cancer because of increased participation in clinical trials. Unfortunately, overall patient participation in cancer clinical studies is low. A key logistical barrier to patient and physician participation is the time required for identification of appropriate clinical trials for individual patients. We introduce the Trial Prospector tool that supports end-to-end management of cancer clinical trial recruitment workflow with (a) structured entry of trial eligibility criteria, (b) automated extraction of patient data from multiple sources, (c) a scalable matching algorithm, and (d) interactive user interface (UI) for physicians with both matching results and a detailed explanation of causes for ineligibility of available trials. We report the results from deployment of Trial Prospector at the National Cancer Institute (NCI)-designated Case Comprehensive Cancer Center (Case CCC) with 1,367 clinical trial eligibility evaluations performed with 100% accuracy. PMID:25506198

A genotype-directed comparative effectiveness trial of Bucindolol and metoprolol succinate for prevention of symptomatic atrial fibrillation/atrial flutter in patients with heart failure: Rationale and design of the GENETIC-AF trial.

PubMed

Piccini, Jonathan P; Connolly, Stuart J; Abraham, William T; Healey, Jeff S; Steinberg, Benjamin A; Al-Khalidi, Hussein R; Dignacco, Patricia; van Veldhuisen, Dirk J; Sauer, William H; White, Michel; Wilton, Stephen B; Anand, Inder S; Dufton, Christopher; Marshall, Debra A; Aleong, Ryan G; Davis, Gordon W; Clark, Richard L; Emery, Laura L; Bristow, Michael R

2018-05-01

Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing heart failure events in patients homozygous for the major allele of the ADRB1 Arg389Gly polymorphism (ADRB1 Arg389Arg genotype). The safety and efficacy of bucindolol for the prevention of AF or atrial flutter (AFL) in these patients has not been proven in randomized trials. The Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Metoprolol Succinate for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure (GENETIC-AF) trial is a multicenter, randomized, double-blinded "seamless" phase 2B/3 trial of bucindolol hydrochloride versus metoprolol succinate, for the prevention of symptomatic AF/AFL in patients with reduced ejection fraction heart failure (HFrEF). Patients with pre-existing HFrEF and recent history of symptomatic AF are eligible for enrollment and genotype screening, and if they are ADRB1 Arg389Arg, eligible for randomization. A total of approximately 200 patients will comprise the phase 2B component and if pre-trial assumptions are met, 620 patients will be randomized at approximately 135 sites to form the Phase 3 population. The primary endpoint is the time to recurrence of symptomatic AF/AFL or mortality over a 24-week follow-up period, and the trial will continue until 330 primary endpoints have occurred. GENETIC-AF is the first randomized trial of pharmacogenetic guided rhythm control, and will test the safety and efficacy of bucindolol compared with metoprolol succinate for the prevention of recurrent symptomatic AF/AFL in patients with HFrEF and an ADRB1 Arg389Arg genotype. (ClinicalTrials.govNCT01970501). Copyright © 2017 Elsevier Inc. All rights reserved.

Liraglutide efficacy and action in non-alcoholic steatohepatitis (LEAN): study protocol for a phase II multicentre, double-blinded, randomised, controlled trial

PubMed Central

Armstrong, Matthew J; Barton, Darren; Gaunt, Piers; Hull, Diana; Guo, Kathy; Stocken, Deborah; Gough, Stephen C L; Tomlinson, Jeremy W; Brown, Rachel M; Hübscher, Stefan G; Newsome, Philip N

2013-01-01

Introduction Non-alcoholic steatohepatitis (NASH) is now the commonest cause of chronic liver disease. Despite this, there are no universally accepted pharmacological therapies for NASH. Liraglutide (Victoza), a human glucagon-like peptide-1 (GLP-1) analogue, has been shown to improve weight loss, glycaemic control and liver enzymes in type 2 diabetes. There is currently a lack of prospective-controlled studies investigating the efficacy of GLP-1 analogues in patients with NASH. Methods and analysis Liraglutide efficacy and action in NASH (LEAN) is a phase II, multicentre, double-blinded, placebo-controlled, randomised clinical trial designed to investigate whether a 48-week treatment with 1.8 mg liraglutide will result in improvements in liver histology in patients with NASH. Adult, overweight (body mass index ≥25 kg/m2) patients with biopsy-confirmed NASH were assessed for eligibility at five recruitment centres in the UK. Patients who satisfied the eligibility criteria were randomly assigned (1:1) to receive once-daily subcutaneous injections of either 1.8 mg liraglutide or liraglutide-placebo (control). Using A'Hern's single stage phase II methodology (significance level 0.05; power 0.90) and accounting for an estimated 20% withdrawal rate, a minimum of 25 patients were randomised to each treatment group. The primary outcome measure will be centrally assessed using an intention-to-treat analysis of the proportion of evaluable patients achieving an improvement in liver histology between liver biopsies at baseline and after 48 weeks of treatment. Histological improvement will be defined as a combination of the disappearance of active NASH and no worsening in fibrosis. Ethics and dissemination The protocol was approved by the National Research Ethics Service (East Midlands—Northampton committee; 10/H0402/32) and the Medicines and Healthcare products Regulatory Agency. Recruitment into the LEAN started in August 2010 and ended in May 2013, with 52 patients randomised. The treatment follow-up of LEAN participants is currently ongoing and is due to finish in July 2014. The findings of this trial will be disseminated through peer-reviewed publications and international presentations. Trial registration clinicaltrials.gov NCT01237119. PMID:24189085

The effectiveness and safety of treatments used for polycystic ovarian syndrome management in adolescents: a systematic review and network meta-analysis protocol.

PubMed

Al Khalifah, Reem A; Flórez, Iván D; Dennis, Brittany; Neupane, Binod; Thabane, Lehana; Bassilious, Ereny

2015-09-23

Polycystic ovarian syndrome (PCOS) is a common reproductive endocrine disease that is seen among adolescent women. Currently, there is limited evidence to support treatment options leading to considerable variation in practice among healthcare specialists. The objective of this study is to review and synthesize all the available evidence on treatment options for PCOS among adolescent women. We will conduct a systematic review of all randomized controlled trials evaluating the use of metformin, oral contraceptive pills as monotherapy, or as combination with pioglitazone, spironolactone, flutamide, and lifestyle interventions in the treatment of PCOS in adolescent women ages 11 to 19 years. The primary outcome measures are menstrual regulation and change hirsutism scores. The secondary outcome measures include acne scores, prevalence of dysglycaemia, BMI, lipid profile, total testosterone level, and adverse events. We will perform literature searches through Ovid Medline, Ovid Embase, and Cochrane Central Register of Controlled Trials (CENTRAL), and gray literature resources. Two reviewers will independently screen titles and abstracts of identified citations, review the full texts of potentially eligible trials, extract information from eligible trials, and assess the risk of bias and quality of the evidence independently. Results of this review will be summarized narratively and quantitatively as appropriate. We will perform a multiple treatment comparison using network meta-analysis to estimate the pooled direct and indirect effects for all PCOS interventions on outcomes if adequate data is available. PCOS treatment poses a clinical challenge to the patients and physicians. This is the first systematic review and network meta-analysis for PCOS treatment in adolescents. We expect that our results will help improve patient care, unify the treatment approaches among specialists, and encourage research for other therapeutic options. PROSPERO CRD42015016148.

Recruitment, screening, and baseline participant characteristics in the WALK 2.0 study: A randomized controlled trial using web 2.0 applications to promote physical activity.

PubMed

Caperchione, Cristina M; Duncan, Mitch J; Rosenkranz, Richard R; Vandelanotte, Corneel; Van Itallie, Anetta K; Savage, Trevor N; Hooker, Cindy; Maeder, Anthony J; Mummery, W Kerry; Kolt, Gregory S

2016-04-15

To describe in detail the recruitment methods and enrollment rates, the screening methods, and the baseline characteristics of a sample of adults participating in the Walk 2.0 Study, an 18 month, 3-arm randomized controlled trial of a Web 2.0 based physical activity intervention. A two-fold recruitment plan was developed and implemented, including a direct mail-out to an extract from the Australian Electoral Commission electoral roll, and other supplementary methods including email and telephone. Physical activity screening involved two steps: a validated single-item self-report instrument and the follow-up Active Australia Questionnaire. Readiness for physical activity participation was also based on a two-step process of administering the Physical Activity Readiness Questionnaire and, where needed, further clearance from a medical practitioner. Across all recruitment methods, a total of 1244 participants expressed interest in participating, of which 656 were deemed eligible. Of these, 504 were later enrolled in the Walk 2.0 trial (77% enrollment rate) and randomized to the Walk 1.0 group (n = 165), the Walk 2.0 group (n = 168), or the Logbook group (n = 171). Mean age of the total sample was 50.8 years, with 65.2% female and 79.1% born in Australia. The results of this recruitment process demonstrate the successful use of multiple strategies to obtain a diverse sample of adults eligible to take part in a web-based physical activity promotion intervention. The use of dual screening processes ensured safe participation in the intervention. This approach to recruitment and physical activity screening can be used as a model for further trials in this area.

Computerized clinical decision support systems for chronic disease management: a decision-maker-researcher partnership systematic review.

PubMed

Roshanov, Pavel S; Misra, Shikha; Gerstein, Hertzel C; Garg, Amit X; Sebaldt, Rolf J; Mackay, Jean A; Weise-Kelly, Lorraine; Navarro, Tamara; Wilczynski, Nancy L; Haynes, R Brian

2011-08-03

The use of computerized clinical decision support systems (CCDSSs) may improve chronic disease management, which requires recurrent visits to multiple health professionals, ongoing disease and treatment monitoring, and patient behavior modification. The objective of this review was to determine if CCDSSs improve the processes of chronic care (such as diagnosis, treatment, and monitoring of disease) and associated patient outcomes (such as effects on biomarkers and clinical exacerbations). We conducted a decision-maker-researcher partnership systematic review. We searched MEDLINE, EMBASE, Ovid's EBM Reviews database, Inspec, and reference lists for potentially eligible articles published up to January 2010. We included randomized controlled trials that compared the use of CCDSSs to usual practice or non-CCDSS controls. Trials were eligible if at least one component of the CCDSS was designed to support chronic disease management. We considered studies 'positive' if they showed a statistically significant improvement in at least 50% of relevant outcomes. Of 55 included trials, 87% (n = 48) measured system impact on the process of care and 52% (n = 25) of those demonstrated statistically significant improvements. Sixty-five percent (36/55) of trials measured impact on, typically, non-major (surrogate) patient outcomes, and 31% (n = 11) of those demonstrated benefits. Factors of interest to decision makers, such as cost, user satisfaction, system interface and feature sets, unique design and deployment characteristics, and effects on user workflow were rarely investigated or reported. A small majority (just over half) of CCDSSs improved care processes in chronic disease management and some improved patient health. Policy makers, healthcare administrators, and practitioners should be aware that the evidence of CCDSS effectiveness is limited, especially with respect to the small number and size of studies measuring patient outcomes.

Computerized clinical decision support systems for chronic disease management: A decision-maker-researcher partnership systematic review

PubMed Central

2011-01-01

Background The use of computerized clinical decision support systems (CCDSSs) may improve chronic disease management, which requires recurrent visits to multiple health professionals, ongoing disease and treatment monitoring, and patient behavior modification. The objective of this review was to determine if CCDSSs improve the processes of chronic care (such as diagnosis, treatment, and monitoring of disease) and associated patient outcomes (such as effects on biomarkers and clinical exacerbations). Methods We conducted a decision-maker-researcher partnership systematic review. We searched MEDLINE, EMBASE, Ovid's EBM Reviews database, Inspec, and reference lists for potentially eligible articles published up to January 2010. We included randomized controlled trials that compared the use of CCDSSs to usual practice or non-CCDSS controls. Trials were eligible if at least one component of the CCDSS was designed to support chronic disease management. We considered studies 'positive' if they showed a statistically significant improvement in at least 50% of relevant outcomes. Results Of 55 included trials, 87% (n = 48) measured system impact on the process of care and 52% (n = 25) of those demonstrated statistically significant improvements. Sixty-five percent (36/55) of trials measured impact on, typically, non-major (surrogate) patient outcomes, and 31% (n = 11) of those demonstrated benefits. Factors of interest to decision makers, such as cost, user satisfaction, system interface and feature sets, unique design and deployment characteristics, and effects on user workflow were rarely investigated or reported. Conclusions A small majority (just over half) of CCDSSs improved care processes in chronic disease management and some improved patient health. Policy makers, healthcare administrators, and practitioners should be aware that the evidence of CCDSS effectiveness is limited, especially with respect to the small number and size of studies measuring patient outcomes. PMID:21824386

Efficacy of oral vs. topical, or combined oral and topical 5-aminosalicylates, in Ulcerative Colitis: systematic review and meta-analysis.

PubMed

Ford, Alexander C; Khan, Khurram J; Achkar, Jean-Paul; Moayyedi, Paul

2012-02-01

Efficacy of 5-aminosalicylic acids (5-ASAs) in ulcerative colitis (UC) has been studied previously in meta-analyses. However, no recent meta-analysis has studied the relative efficacies of differing routes of administration. MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through May 2011). Eligible trials recruited adults with mildly to moderately active UC, or quiescent UC, and compared oral 5-ASAs with either topical 5-ASAs or a combination of oral and topical 5-ASAs. Dichotomous data were pooled to obtain relative risk (RR) of failure to achieve remission in active UC, and RR of relapse of disease activity in quiescent UC, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. The search identified 3,061 citations, and 12 randomized controlled trials (RCTs) were eligible. Four compared topical with oral 5-ASAs in active UC remission, with an RR of no remission with topical 5-ASAs of 0.82 (95% CI=0.52-1.28). Four trials compared combined with oral 5-ASAs in active UC (RR of no remission=0.65; 95% CI=0.47-0.91; NNT=5). Three RCTs compared intermittent topical with oral 5-ASAs in preventing relapse of quiescent UC (RR=0.64; 95% CI=0.43-0.95; NNT=4), and two compared combined with oral 5-ASAs (RR of relapse=0.48; 95% CI=0.17-1.38). Combined 5-ASA therapy appeared superior to oral 5-ASAs for induction of remission of mildly to moderately active UC. Intermittent topical 5-ASAs appeared superior to oral 5-ASAs for preventing relapse of quiescent UC.

Paramedic Initiated Lisinopril For Acute Stroke Treatment (PIL-FAST): results from the pilot randomised controlled trial

PubMed Central

Shaw, Lisa; Price, Christopher; McLure, Sally; Howel, Denise; McColl, Elaine; Younger, Paul; Ford, Gary A

2014-01-01

Background High blood pressure (BP) during acute stroke is associated with poorer stroke outcome. Trials of treatments to lower BP have not resulted in improved outcome, but this may be because treatment commenced too late. Emergency medical service staff (paramedics) are uniquely placed to administer early treatment; however, experience of prehospital randomised controlled trials (RCTs) is very limited. Methods We conducted a pilot RCT to determine the feasibility of a definitive prehospital BP-lowering RCT in acute stroke. Paramedics were trained to identify, consent and deliver a first dose of lisinopril or placebo to adults with suspected stroke and hypertension while responding to the emergency call. Further treatment continued in hospital. Study eligibility, recruitment rate, completeness of receipt of study medication and clinical data (eg, BP) were collected to inform the design of a definitive RCT. Results In 14 months, 14 participants (median age=73 years, median National Institute of Health Stroke Scale=4) were recruited and received the prehospital dose of medication. Median time from stroke onset (as assessed by paramedic) to treatment was 70 min. Four participants completed 7 days of study treatment. Of ambulance transported suspected stroke patients, 1% were both study eligible and attended by a PIL-FAST paramedic. Conclusions It is possible to conduct a paramedic initiated double-blind RCT of a treatment for acute stroke. However, to perform a definitive RCT in a reasonable timescale, a large number of trained paramedics across several ambulance services would be needed to recruit the number of patients likely to be required. Clinical trial registration http://www.clinicaltrials.gov. Unique identifier: NCT01066572. PMID:24078198

Randomized controlled trial comparing telephone and mail follow-up for recruitment of participants into a clinical trial of colorectal cancer screening.

PubMed

Wong, Arthur D; Kirby, John; Guyatt, Gordon H; Moayyedi, Paul; Vora, Parag; You, John J

2013-02-11

Investigators often face challenges when recruiting participants into randomized controlled trials (RCTs). Some data suggest that telephone reminders may lead to greater participant enrollment. Patients aged 50 to 70 years from family practice rosters were initially mailed invitations to participate in an RCT of colorectal cancer screening. Patients who did not respond were randomly allocated to follow-up invitations by either telephone or mail four weeks after the initial invitation. The primary outcome was attendance for eligibility screening with the study nurse. After mailing invitations to 1,348 patients, 104 patients were initially enrolled in the RCT of colon cancer screening. Of 952 patients who did not respond to the initial mailed invitation, we randomly allocated 480 to follow-up invitation by telephone and 472 to follow-up invitation by mail. Attendance for eligibility screening with the study nurse was more frequent when non-responders were followed-up by telephone (84/480, 17.5%) than by mail (43/472, 9.1%) (relative risk (RR) 1.92, 95% confidence interval (CI) 1.36 to 2.71, P < 0.001). Enrollment into the RCT was also greater among patients followed-up by telephone (59/480, 12.3%) compared to those followed-up by mail (35/472, 7.4%) (RR 1.66, 95% CI 1.11 to 2.47, P=0.01). Telephone-based follow-up results in greater enrollment compared to a mail-based method. Our findings should be of interest to investigators conducting RCTs, particularly trials of screening interventions involving asymptomatic participants for which volunteer participation may be challenging. Clinicaltrials.gov NCT00865527.

A systematic review of school-based eHealth interventions targeting alcohol use, smoking, physical inactivity, diet, sedentary behaviour and sleep among adolescents: a review protocol.

PubMed

Champion, Katrina E; Newton, Nicola C; Spring, Bonnie; Wafford, Q Eileen; Parmenter, Belinda J; Teesson, Maree

2017-12-06

Six key behavioural risk factors (risky alcohol use, smoking, poor diet, physical inactivity, sedentary behaviour and unhealthy sleep patterns) have been identified as strong determinants of chronic disease, such as cardiovascular disease, diabetes and cancers. School-based interventions targeting these multiple health risk behaviours among adolescents have the potential to halt the trajectory towards later disease, whilst online and mobile technology interventions offer advantages in terms of student engagement, reach and scalability. Despite this, the efficacy of eHealth school-based interventions targeting these six health risk behaviours among adolescents has not been evaluated. The proposed systematic review aims to address this by determining the nature and efficacy of existing eHealth school-based interventions targeting multiple health risk behaviours among adolescents. A systematic search of the MEDLINE, Embase, PsycINFO and Cochrane Library databases will be conducted to identify eligible published papers. Eligible studies will be randomised controlled trials, including cluster randomised controlled trials, of interventions targeting two or more of the following lifestyle risk behaviours: alcohol use, smoking, poor diet, physical inactivity, sedentary behaviour and sleep. Eligible studies will be those evaluating interventions delivered in a secondary school setting among participants 11-18 years of age, via an eHealth platform (Internet, computers of mobile technology). Two reviewers will independently screen studies for eligibility, extract data and assess the risk of bias. Study outcomes will be summarised in a narrative synthesis, and meta-analyses will be conducted where it is appropriate to combine studies. It is anticipated that the results from this review will serve to inform the development of future eHealth multiple health behaviour interventions for adolescents by identifying common characteristics of effective programs and highlighting knowledge gaps in the evidence base. PROSPERO CRD42017072163.

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.

Treatment of vaginal candidiasis for the prevention of preterm birth: a systematic review and meta-analysis.

PubMed

Roberts, Christine L; Algert, Charles S; Rickard, Kristen L; Morris, Jonathan M

2015-03-21

Recognition that ascending infection leads to preterm birth has led to a number of studies that have evaluated the treatment of vaginal infections in pregnancy to reduce preterm birth rates. However, the role of candidiasis is relatively unexplored. Our aim was to undertake a systematic review and meta-analysis to assess whether treatment of pregnant women with vulvovaginal candidiasis reduces preterm birth rates and other adverse birth outcomes. We undertook a systematic review and meta-analysis of published randomised controlled trials (RCTs) in which pregnant women were treated for vulvovaginal candidiasis (compared to placebo or no treatment) and where preterm birth was reported as an outcome. Trials were identified by searching the Cochrane Central Register of Controlled Trials, Medline and Embase databases to January 2014. Trial eligibility and outcomes were pre-specified. Two reviewers independently assessed the studies against the agreed criteria and extracted relevant data using a standard data extraction form. Meta-analysis was used to calculate pooled rate ratios (RR) and 95% confidence intervals (CI) using a fixed-effects model. There were two eligible RCTs both among women with asymptomatic candidiasis, with a total of 685 women randomised. Both trials compared treatment with usual care (no screening for, or treatment of, asymptomatic candidiasis). Data from one trial involved a post-hoc subgroup analysis (n = 586) of a larger trial of treatment of 4,429 women with asymptomatic infections in pregnancy and the other was a pilot study (n = 99). There was a significant reduction in spontaneous preterm births in treated compared with untreated women (meta-analysis RR = 0.36, 95% CI = 0.17 to 0.75). Other outcomes were reported by one or neither trial. This systematic review found two trials comparing the treatment of asymptomatic vaginal candidiasis in pregnancy for the outcome of preterm birth. Although the effect estimate suggests that treatment of asymptomatic candidiasis may reduce the risk of preterm birth, the result needs to be interpreted with caution as the primary driver for the pooled estimate comes from a post-hoc (unplanned) subgroup analysis. A prospective trial with sufficient power to answer the clinical question 'does treatment of asymptomatic candidiasis in early pregnancy prevent preterm birth' is warranted. PROSPERO CRD42014009241.

Effects of interpretive nutrition labels on consumer food purchases: the Starlight randomized controlled trial.

PubMed

Ni Mhurchu, Cliona; Volkova, Ekaterina; Jiang, Yannan; Eyles, Helen; Michie, Jo; Neal, Bruce; Blakely, Tony; Swinburn, Boyd; Rayner, Mike

2017-03-01

Background: Nutrition labeling is a prominent policy to promote healthy eating. Objective: We aimed to evaluate the effects of 2 interpretive nutrition labels compared with a noninterpretive label on consumer food purchases. Design: In this parallel-group randomized controlled trial, we enrolled household shoppers across New Zealand who owned smartphones and were aged ≥18 y. Eligible participants were randomly assigned (1:1:1) to receive either traffic light labels (TLLs), Health Star Rating labels (HSRs), or a control [nutrition information panel (NIP)]. Smartphone technology allowed participants to scan barcodes of packaged foods and to receive allocated labels on their smartphone screens. The primary outcome was the mean healthiness of all packaged food purchases over the 4-wk intervention period, which was measured by using the Food Standards Australia New Zealand Nutrient Profiling Scoring Criterion (NPSC). Results: Between October 2014 and November 2015, 1357 eligible shoppers were randomly assigned to TLL ( n = 459), HSR ( n = 443), or NIP ( n = 455) labels. Overall difference in the mean transformed NPSC score for the TLL group compared with the NIP group was -0.20 (95% CI: -0.94, 0.54; P = 0.60). The corresponding difference for HSR compared with NIP was -0.60 (95% CI: -1.35, 0.15; P = 0.12). In an exploratory per-protocol analysis of participants who used the labeling intervention more often than average ( n = 423, 31%), those who were assigned to TLL and HSR had significantly better NPSC scores [TLL compared with NIP: -1.33 (95% CI: -2.63, -0.04; P = 0.04); HSR compared with NIP: -1.70 (95% CI: -2.97, -0.43; P = 0.01)]. Shoppers who were randomly assigned to HSR and TLL also found the labels significantly more useful and easy to understand than the NIP (all P values <0.001). Conclusions: At the relatively low level of use observed in this trial, interpretive nutrition labels had no significant effect on food purchases. However, shoppers who used interpretive labels found them to be significantly more useful and easy to understand, and compared with frequent NIP users, frequent TLL and HSR users had significantly healthier food purchases. This trial was registered at the Australian New Zealand Clinical Trials Registry (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366446&isReview=true) as ACTRN12614000644662. © 2017 American Society for Nutrition.

Promoting Recruitment using Information Management Efficiently (PRIME): study protocol for a stepped-wedge cluster randomised controlled trial within the REstart or STop Antithrombotics Randomised Trial (RESTART).

PubMed

Maxwell, Amy E; Dennis, Martin; Rudd, Anthony; Weir, Christopher J; Parker, Richard A; Al-Shahi Salman, Rustam

2017-03-01

Research into methods to boost recruitment has been identified as the highest priority for randomised controlled trial (RCT) methodological research in the United Kingdom. Slow recruitment delays the delivery of research and inflates costs. Using electronic patient records has been shown to boost recruitment to ongoing RCTs in primary care by identifying potentially eligible participants, but this approach remains relatively unexplored in secondary care, and for stroke in particular. The REstart or STop Antithrombotics Randomised Trial (RESTART; ISRCTN71907627) is an ongoing RCT of secondary prevention after stroke due to intracerebral haemorrhage. Promoting Recruitment using Information Management Efficiently (PRIME) is a stepped-wedge cluster randomised trial of a complex intervention to help RESTART sites increase their recruitment and attain their own target numbers of participants. Seventy-two hospital sites that were located in England, Wales or Scotland and were active in RESTART in June 2015 opted into PRIME. Sites were randomly allocated (using a computer-generated block randomisation algorithm, stratified by hospital location in Scotland vs. England/Wales) to one of 12 months in which the intervention would be delivered. All sites began in the control state. The intervention was delivered by a recruitment co-ordinator via a teleconference with each site. The intervention involved discussing recruitment strategies, providing software for each site to extract from their own stroke audit data lists of patients who were potentially eligible for RESTART, and a second teleconference to review progress 6 months later. The recruitment co-ordinator was blinded to the timing of the intervention until 2 months before it was due at a site. Staff at RESTART sites were blinded to the nature and timing of the intervention. The primary outcome is the total number of patients randomised into RESTART per month per site and will be analysed in a negative binomial generalised linear mixed model. PRIME began in September 2015. The last intervention was delivered in August 2016. Six-month follow-up will be complete in February 2017. The final results of PRIME will be analysed and disseminated in 2017. The PRIME study was registered in the Northern Ireland Hub for Trials Methodology Research Studies Within a Trial (SWAT) repository (SWAT22) on 23 December 2015.

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.

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.

The Effectiveness Of Social Media (Facebook) Compared With More Traditional Advertising Methods for Recruiting Eligible Participants To Health Research Studies: A Randomized, Controlled Clinical Trial

PubMed Central

Thow, Megan; Ferguson, Stuart G

2016-01-01

Background Recruiting participants for research studies can be difficult and costly. The popularity of social media platforms (eg, Facebook) has seen corresponding growth in the number of researchers turning to social networking sites and their embedded advertising frameworks to locate eligible participants for studies. Compared with traditional recruitment strategies such as print media, social media advertising has been shown to be favorable in terms of its reach (especially with hard-to-reach populations), cost effectiveness, and usability. However, to date, no studies have examined how participants recruited via social media progress through a study compared with those recruited using more traditional recruitment strategies. Objectives (1) Examine whether visiting the study website prior to being contacted by researchers creates self-screened participants who are more likely to progress through all study phases (eligible, enrolled, completed); (2) compare conversion percentages and cost effectiveness of each recruitment method at each study phase; and, (3) compare demographic and smoking characteristics of participants recruited through each strategy to determine if they attract similar samples. Methods Participants recruited to a smoking cessation clinical trial were grouped by how they had become aware of the study: via social media (Facebook) or traditional media (eg, newspaper, flyers, radio, word of mouth). Groups were compared based on throughput data (conversion percentages and cost) as well as demographic and smoking characteristics. Results Visiting the study website did not result in individuals who were more likely to be eligible for (P=.24), enroll in (P=.20), or complete (P=.25) the study. While using social media was more cost effective than traditional methods when we examined earlier endpoints of the recruitment process (cost to obtain a screened respondent: AUD $22.73 vs $29.35; cost to obtain an eligible respondent: $37.56 vs $44.77), it was less cost effective in later endpoints (cost per enrolled participant: $56.34 vs $52.33; cost per completed participant: $103.66 vs $80.43). Participants recruited via social media were more likely to be younger (P=.001) and less confident in their quit attempts (P=.004) compared to those recruited via traditional methods. Conclusions Our study suggests that while social media advertising may be effective in generating interest from potential participants, this strategy’s ability to attract conscientious recruits is more questionable. Researchers considering using online resources (eg, social media advertising, matrix codes) should consider including prescreening questions to promote conversion percentages. Ultimately, researchers seeking to maximize their recruitment budget should consider using a combination of advertising strategies. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN 12614000329662; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365947l (Archived by WebCite at http://www.webcitation.org/6jc6zXWZI) PMID:27511829

The Effectiveness Of Social Media (Facebook) Compared With More Traditional Advertising Methods for Recruiting Eligible Participants To Health Research Studies: A Randomized, Controlled Clinical Trial.

PubMed

Frandsen, Mai; Thow, Megan; Ferguson, Stuart G

2016-08-10

Recruiting participants for research studies can be difficult and costly. The popularity of social media platforms (eg, Facebook) has seen corresponding growth in the number of researchers turning to social networking sites and their embedded advertising frameworks to locate eligible participants for studies. Compared with traditional recruitment strategies such as print media, social media advertising has been shown to be favorable in terms of its reach (especially with hard-to-reach populations), cost effectiveness, and usability. However, to date, no studies have examined how participants recruited via social media progress through a study compared with those recruited using more traditional recruitment strategies. (1) Examine whether visiting the study website prior to being contacted by researchers creates self-screened participants who are more likely to progress through all study phases (eligible, enrolled, completed); (2) compare conversion percentages and cost effectiveness of each recruitment method at each study phase; and, (3) compare demographic and smoking characteristics of participants recruited through each strategy to determine if they attract similar samples. Participants recruited to a smoking cessation clinical trial were grouped by how they had become aware of the study: via social media (Facebook) or traditional media (eg, newspaper, flyers, radio, word of mouth). Groups were compared based on throughput data (conversion percentages and cost) as well as demographic and smoking characteristics. Visiting the study website did not result in individuals who were more likely to be eligible for (P=.24), enroll in (P=.20), or complete (P=.25) the study. While using social media was more cost effective than traditional methods when we examined earlier endpoints of the recruitment process (cost to obtain a screened respondent: AUD $22.73 vs $29.35; cost to obtain an eligible respondent: $37.56 vs $44.77), it was less cost effective in later endpoints (cost per enrolled participant: $56.34 vs $52.33; cost per completed participant: $103.66 vs $80.43). Participants recruited via social media were more likely to be younger (P=.001) and less confident in their quit attempts (P=.004) compared to those recruited via traditional methods. Our study suggests that while social media advertising may be effective in generating interest from potential participants, this strategy's ability to attract conscientious recruits is more questionable. Researchers considering using online resources (eg, social media advertising, matrix codes) should consider including prescreening questions to promote conversion percentages. Ultimately, researchers seeking to maximize their recruitment budget should consider using a combination of advertising strategies. Australian New Zealand Clinical Trials Registry ACTRN 12614000329662; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365947l (Archived by WebCite at http://www.webcitation.org/6jc6zXWZI).

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.

Clinical trials in rheumatoid arthritis: a status report from the ClinicalTrials.gov website.

PubMed

Paul, Jisna R; Ranganathan, Prabha

2012-06-01

The aims of this study are to describe the characteristics of clinical trials in rheumatoid arthritis (RA) listed in ClinicalTrials.gov and examine existing trends in study design, funding sources, outcomes, and drugs under investigation. We conducted a survey of ongoing clinical trials in RA registered in the ClinicalTrials.gov website. We used the advanced search option and applied the following inclusion criteria, "rheumatoid arthritis", "open studies", "interventional", and "adults 18 years or older". Of 127 eligible trials, 53.5% of the studies were either phase 3 or 4, and 40.2% were phase 1, 2, and 2/3. Two-thirds of the trials were randomized (70.9%), and over half were, in addition, double-blinded (53.5%) and placebo-controlled (53.5%). Universities were listed as the primary sponsor for 18.9% of the trials and pharmaceutical industry for 73.2%. Majority of the trials were multi-center studies (93%) conducted outside the United States (54.3%). The most frequently used endpoint was drug efficacy (54.3%) followed by drug safety (25.2%). Most industry-funded trials were open for less than 12 months, whereas most university-funded trials were open for more than 24 months (58% each). Biologic therapies were the focus of most trials in the registry (78.5%). Randomized, double-blinded, placebo-controlled, phase 3 and 4 trials form the majority of ongoing clinical trials in RA. The preponderance of industry funding of RA trials and the short duration of such trials are troubling trends which need to be addressed.

Evaluating an in-home multicomponent cognitive behavioural programme to manage concerns about falls and associated activity avoidance in frail community-dwelling older people: Design of a randomised control trial [NCT01358032

PubMed Central

2011-01-01

Background Concerns about falls are frequently reported by older people. These concerns can have serious consequences such as an increased risk of falls and the subsequent avoidance of activities. Previous studies have shown the effectiveness of a multicomponent group programme to reduce concerns about falls. However, owing to health problems older people may not be able to attend a group programme. Therefore, we adapted the group approach to an individual in-home programme. Methods/Design A two-group randomised controlled trial has been developed to evaluate the in-home multicomponent cognitive behavioural programme to manage concerns about falls and associated activity avoidance in frail older people living in the community. Persons were eligible for study if they were 70 years of age or over, perceived their general health as fair or poor, had at least some concerns about falls and associated avoidance of activity. After screening for eligibility in a random sample of older people, eligible persons received a baseline assessment and were subsequently allocated to the intervention or control group. Persons assigned to the intervention group were invited to participate in the programme, while those assigned to the control group received care as usual. The programme consists of seven sessions, comprising three home visits and four telephone contacts. The sessions are aimed at instilling adaptive and realistic views about falls, as well as increasing activity and safe behaviour. An effect evaluation, a process evaluation and an economic evaluation are conducted. Follow-up measurements for the effect evaluation are carried out 5 and 12 months after the baseline measurement. The primary outcomes of the effect evaluation are concerns about falls and avoidance of activity as a result of these concerns. Other outcomes are disability and falls. The process evaluation measures: the population characteristics reached; protocol adherence by facilitators; protocol adherence by participants (engagement in exposure and homework); opinions about the programme of participants and facilitators; perceived benefits and achievements; and experienced barriers. The economic evaluation examines the impact on health-care utilisation, as well as related costs. Discussion A total number of 389 participants is included in the study. Final results are expected in 2012. Trial registration NCT01358032 PMID:21933436

Rectal 5-aminosalicylic acid for induction of remission in ulcerative colitis.

PubMed

Marshall, John K; Thabane, Marroon; Steinhart, A Hillary; Newman, Jamie R; Anand, Anju; Irvine, E Jan

2010-01-20

5-Aminosalicylates (5-ASA) are considered a first-line therapy for inducing and maintaining remission of mild to moderately active ulcerative colitis (UC). When inflammation in UC is limited to the distal colon, 5-ASA can also be administered rectally as a suppository, enema or foam. A systematic review was undertaken to evaluate the efficacy of rectal 5-ASA for treating active distal UC. Electronic searches of the MEDLINE database (1966-2008), the Cochrane Central Register of Controlled Trials and the Cochrane IBD/FBD Group Specialized Trials Register were supplemented by manual reviews of reference listings and conference proceedings. Randomized trials comparing rectal 5-ASA to placebo or another active therapy were eligible for inclusion. Eligible trials enrolled patients with a distal disease margin less than 60 cm from the anal verge or distal to the splenic flexure. Trials that enrolled subjects less than 12 years of age were excluded. Eligibility was assessed by three authors. Data were extracted by two authors using standardized forms. Pooled odds ratios (POR) for inducing improvement and remission by symptomatic, endoscopic and histologic criteria were calculated using an intention to treat principle. Fixed effects models were used unless heterogeneity was encountered within groups (P < 0.10), where random effects models were used. All statistical analyses were performed using RevMan 5. Where sufficient data were available, subgroup analyses were performed for disease extent, total daily 5-ASA dose, 5-ASA formulation (enema,suppository, foam) and the type of control intervention (placebo or another active therapy). Thirty-eight studies fulfilled the inclusion criteria. Rectal 5-ASA was superior to placebo for inducing symptomatic, endoscopic and histological improvement and remission, with POR for symptomatic improvement 8.87 (8 trials, 95% CI: 5.30 to 14.83; P < 0.00001), endoscopic improvement 11.18 (5 trials, 95% CI 5.99 to 20.88; P < 0.00001), histologic improvement 7.69 (6 trials, 95% CI 3.26 to 18.12; P < 0.00001), symptomatic remission 8.30 (8 trials, 95% CI 4.28 to 16.12; P < 0.00001), endoscopic remission 5.31 (7 trials, 95% CI 3.15 to 8.92; P < 0.00001), and histologic remission 6.28 (5 trials, 95% CI 2.74 to 14.40; P < 0.0001). Rectal 5-ASA was superior to rectal corticosteroids for inducing symptomatic improvement and remission with POR 1.56 (6 trials, 95% CI 1.15 to 2.11; P = 0.004) and 1.65 (6 trials, 95% CI 1.11 to 2.45; P = 0.01), respectively. Rectal 5-ASA was not superior to oral 5-ASA for symptomatic improvement (POR 2.25; 95% CI 0.53 to 19.54; P = 0.27). Neither total daily dose nor 5-ASA formulation affected treatment response. Rectal 5-ASA should be considered a first-line therapy for patients with mild to moderately active distal UC. The optimal total daily dose and dose frequency of 5-ASA remain to be determined. Future research should define differences in efficacy among patient subgroups defined by proximal disease margin and disease activity. There is a strong need for consensus standardization of outcome measurements for clinical trials in ulcerative colitis.

Massage therapy for fibromyalgia: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Li, Yan-hui; Wang, Feng-yun; Feng, Chun-qing; Yang, Xia-feng; Sun, Yi-hua

2014-01-01

Although some studies evaluated the effectiveness of massage therapy for fibromyalgia (FM), the role of massage therapy in the management of FM remained controversial. The purpose of this systematic review is to evaluate the evidence of massage therapy for patients with FM. Electronic databases (up to June 2013) were searched to identify relevant studies. The main outcome measures were pain, anxiety, depression, and sleep disturbance. Two reviewers independently abstracted data and appraised risk of bias. The risk of bias of eligible studies was assessed based on Cochrane tools. Standardised mean difference (SMD) and 95% confidence intervals (CI) were calculated by more conservative random-effects model. And heterogeneity was assessed based on the I(2) statistic. Nine randomized controlled trials involving 404 patients met the inclusion criteria. The meta-analyses showed that massage therapy with duration ≥ 5 weeks significantly improved pain (SMD, 0.62; 95% CI 0.05 to 1.20; p = 0.03), anxiety (SMD, 0.44; 95% CI 0.09 to 0.78; p = 0.01), and depression (SMD, 0.49; 95% CI 0.15 to 0.84; p = 0.005) in patients with FM, but not on sleep disturbance (SMD, 0.19; 95% CI -0.38 to 0.75; p = 0.52). Massage therapy with duration ≥ 5 weeks had beneficial immediate effects on improving pain, anxiety, and depression in patients with FM. Massage therapy should be one of the viable complementary and alternative treatments for FM. However, given fewer eligible studies in subgroup meta-analyses and no evidence on follow-up effects, large-scale randomized controlled trials with long follow-up are warrant to confirm the current findings.

Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial.

PubMed

Pozzoni, Pietro; Riva, Alessia; Bellatorre, Alessandro Giacco; Amigoni, Maria; Redaelli, Elena; Ronchetti, Anna; Stefani, Mariangela; Tironi, Rosangela; Molteni, Edoardo Ennio; Conte, Dario; Casazza, Giovanni; Colli, Agostino

2012-06-01

Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Probiotics were effective in preventing AAD and CDAD in several randomized controlled trials. This study was aimed at testing the effect of Saccharomyces boulardii on the occurrence of AAD and CDAD in hospitalized patients. A single-center, randomized, double-blind, placebo-controlled, parallel-group trial was performed. Patients being prescribed antibiotics or on antibiotic therapy for <48 h were eligible. Exclusion criteria were ongoing diarrhea, recent assumption of probiotics, lack of informed consent, inability to ingest capsules, and severe pancreatitis. Patients received a capsule containing S. boulardii or an indistinguishable placebo twice daily within 48 h of beginning antibiotic therapy, continued treatment for 7 days after antibiotic withdrawal, and were followed for 12 weeks after ending antibiotic treatment. Of 562 consecutive eligible patients, 275 patients aged 79.2 ± 9.8 years (134 on placebo) were randomized and 204 aged 78.4 ± 10.0 years (98 on placebo) completed the follow-up. AAD developed in 13.3% (13/98) of the patients receiving placebo and in 15.1% (16/106) of those receiving S. boulardii (odds ratio for S. boulardii vs. placebo, 1.16; 95% confidence interval (CI), 0.53-2.56). Five cases of CDAD occurred, 2 in the placebo group (2.0%) and 3 in the probiotic group (2.8%; odds ratio for S. boulardii vs. placebo, 1.40; 95% CI, 0.23-8.55). There was no difference in mortality rates (12.7% vs. 15.6%, P=0.60). In elderly hospitalized patients, S. boulardii was not effective in preventing the development of AAD.

Comparison of the effectiveness of whole-brain radiotherapy plus temozolomide versus whole-brain radiotherapy in treating brain metastases based on a systematic review of randomized controlled trials.

PubMed

Bai, Gui-Rong; An, Jin-Bing; Chu, Yang; Wang, Xiang-Yang; Li, Shu-Ming; Yan, Kai-Jing; Lü, Fu-Rong; Gu, Ning; Griffin, Amanda N; Sun, Bin-Yuan; Li, Wei; Wang, Guo-Cheng; Zhou, Shui-Ping; Sun, He; Liu, Chang-Xiao

2016-01-01

Temozolomide (TMZ) combination with whole-brain radiotherapy (WBRT) has been tested by many randomized controlled trials in the treatment of brain metastases (BMs) in China and other countries. We performed an up-to-date meta-analysis to determine (i) the log odds ratios (LORs) of objective response (ORR) and adverse effects (AEs) for all-grade, and (ii) the T value of mean overall survival in patients with BMs treated with WBRT combined with TMZ versus WBRT alone. PubMed, Chinese National Knowledge Infrastructure, and WanFang Data were searched for articles published up to 28 January 2015. Eligible studies were selected according to the PRISMA statement. ORR, AEs, and 95% confidence intervals were calculated using random-effects models. Eighteen studies were included in our analysis. A total of 1028 participants were enrolled. Summary LORs of ORR were 1.0239 (P<0.0001) on comparing WBRT plus TMZ with WBRT ORR (n=17). The overall mean difference of mean overall survival (n=17) between TMZ plus WBRT and WBRT was 2.2505 weeks (P=0.02185). There was a significant difference between WBRT plus TMZ and WBRT alone with a LOR of AEs for all-grade of (i) 0.923 for gastrointestinal toxicity and (ii) 0.7978 for myelosuppression. Sensitivity analysis and subgroup analysis were also performed. The 18 eligible randomized controlled trials demonstrated that the combination of WBRT and TMZ significantly improves the ORR and is statistically insignificant in prolonging the survival of patients with BMs. In addition, an increase in the incidence of gastrointestinal toxicity and myelosuppression was significant for all-grade.

Effectiveness of psychological interventions delivered by non-psychologists on low back pain and disability: a qualitative systematic review.

PubMed

Bostick, Geoff P

2017-11-01

Psychological treatments delivered by non-psychologists have been proposed as a way to increase access to care to address important psychological barriers to recovery in people with low back pain (LBP). This review aimed to synthesize randomized controlled trials (RCTs) that assess the effectiveness of psychological interventions delivered by non-psychologists in reducing pain intensity and disability in adults with LBP, compared with usual care. A systematic review without meta-analysis was carried out. Randomized controlled trials including adult patients with all types of musculoskeletal LBP were eligible. Interventions included those based on psychological principles and delivered by non-psychologists. The primary outcomes of interest were self-reported pain intensity and disability. Information sources included Medline, EMBASE, and the Cochrane Central Registrar for Controlled Trials. The Cochrane Collaboration's tool for assessing risk of bias was used for the evaluation of internal validity. There were 1,101 records identified, 159 were assessed for eligibility, 16 were critically appraised, and 11 studies were included. Mild to moderate risk of bias was present in the included studies, with personnel and patient blinding, treatment fidelity, and attrition being the most common sources of bias. Considerable heterogeneity existed for patient population, intervention components, and comparison groups. Although most studies demonstrated statistical and clinical improvements in pain and disability, few were statistically superior to the comparison group. Consistent with the broader psychological literature, psychological interventions delivered by non-psychologists have modest effects on low back pain and disability. Additional high quality research is needed to understand what patients are likely to respond to psychological interventions, the appropriate dose to achieve the desired outcome, the amount of training required to implement psychological interventions, and the optimal procedures to ensure treatment fidelity. Copyright © 2017 Elsevier Inc. All rights reserved.

Massage Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Li, Yan-hui; Wang, Feng-yun; Feng, Chun-qing; Yang, Xia-feng; Sun, Yi-hua

2014-01-01

Background Although some studies evaluated the effectiveness of massage therapy for fibromyalgia (FM), the role of massage therapy in the management of FM remained controversial. Objective The purpose of this systematic review is to evaluate the evidence of massage therapy for patients with FM. Methods Electronic databases (up to June 2013) were searched to identify relevant studies. The main outcome measures were pain, anxiety, depression, and sleep disturbance. Two reviewers independently abstracted data and appraised risk of bias. The risk of bias of eligible studies was assessed based on Cochrane tools. Standardised mean difference (SMD) and 95% confidence intervals (CI) were calculated by more conservative random-effects model. And heterogeneity was assessed based on the I2 statistic. Results Nine randomized controlled trials involving 404 patients met the inclusion criteria. The meta-analyses showed that massage therapy with duration ≥5 weeks significantly improved pain (SMD, 0.62; 95% CI 0.05 to 1.20; p = 0.03), anxiety (SMD, 0.44; 95% CI 0.09 to 0.78; p = 0.01), and depression (SMD, 0.49; 95% CI 0.15 to 0.84; p = 0.005) in patients with FM, but not on sleep disturbance (SMD, 0.19; 95% CI −0.38 to 0.75; p = 0.52). Conclusion Massage therapy with duration ≥5 weeks had beneficial immediate effects on improving pain, anxiety, and depression in patients with FM. Massage therapy should be one of the viable complementary and alternative treatments for FM. However, given fewer eligible studies in subgroup meta-analyses and no evidence on follow-up effects, large-scale randomized controlled trials with long follow-up are warrant to confirm the current findings. PMID:24586677

An organisational change intervention for increasing the delivery of smoking cessation support in addiction treatment centres: study protocol for a randomized controlled trial.

PubMed

Bonevski, Billie; Guillaumier, Ashleigh; Shakeshaft, Anthony; Farrell, Michael; Tzelepis, Flora; Walsberger, Scott; D'Este, Catherine; Paul, Chris; Dunlop, Adrian; Searles, Andrew; Kelly, Peter; Fry, Rae; Stirling, Robert; Fowlie, Carrie; Skelton, Eliza

2016-06-14

The provision of smoking cessation support in Australian drug and alcohol treatment services is sub-optimal. This study examines the cost-effectiveness of an organisational change intervention to reduce smoking amongst clients attending drug and alcohol treatment services. A cluster-randomised controlled trial will be conducted with drug and alcohol treatment centres as the unit of randomisation. Biochemically verified (carbon monoxide by breath analysis) client 7-day-point prevalence of smoking cessation at 6 weeks will be the primary outcome measure. The study will be conducted in 33 drug and alcohol treatment services in four mainland states and territories of Australia: New South Wales, Australian Capital Territory, Queensland, and South Australia. Eligible services are those with ongoing client contact and that include pharmacotherapy services, withdrawal management services, residential rehabilitation, counselling services, and case management services. Eligible clients are those aged over 16 years who are attending their first of a number of expected visits, are self-reported current smokers, proficient in the English language, and do not have severe untreated mental illness as identified by the service staff. Control services will continue to provide usual care to the clients. Intervention group services will receive an organisational change intervention, including assistance in developing smoke-free policies, nomination of champions, staff training and educational client and service resources, and free nicotine replacement therapy in order to integrate smoking cessation support as part of usual client care. If effective, the organisational change intervention has clear potential for implementation as part of the standard care in drug and alcohol treatment centres. Australian and New Zealand Clinical Trials Registry, ACTRN12615000204549 . Registered on 3 March 2015.

What's in a name? The challenge of describing interventions in systematic reviews: analysis of a random sample of reviews of non-pharmacological stroke interventions

PubMed Central

Hoffmann, Tammy C; Walker, Marion F; Langhorne, Peter; Eames, Sally; Thomas, Emma; Glasziou, Paul

2015-01-01

Objective To assess, in a sample of systematic reviews of non-pharmacological interventions, the completeness of intervention reporting, identify the most frequently missing elements, and assess review authors’ use of and beliefs about providing intervention information. Design Analysis of a random sample of systematic reviews of non-pharmacological stroke interventions; online survey of review authors. Data sources and study selection The Cochrane Library and PubMed were searched for potentially eligible systematic reviews and a random sample of these assessed for eligibility until 60 (30 Cochrane, 30 non-Cochrane) eligible reviews were identified. Data collection In each review, the completeness of the intervention description in each eligible trial (n=568) was assessed by 2 independent raters using the Template for Intervention Description and Replication (TIDieR) checklist. All review authors (n=46) were invited to complete a survey. Results Most reviews were missing intervention information for the majority of items. The most incompletely described items were: modifications, fidelity, materials, procedure and tailoring (missing from all interventions in 97%, 90%, 88%, 83% and 83% of reviews, respectively). Items that scored better, but were still incomplete for the majority of reviews, were: ‘when and how much’ (in 31% of reviews, adequate for all trials; in 57% of reviews, adequate for some trials); intervention mode (in 22% of reviews, adequate for all trials; in 38%, adequate for some trials); and location (in 19% of reviews, adequate for all trials). Of the 33 (71%) authors who responded, 58% reported having further intervention information but not including it, and 70% tried to obtain information. Conclusions Most focus on intervention reporting has been directed at trials. Poor intervention reporting in stroke systematic reviews is prevalent, compounded by poor trial reporting. Without adequate intervention descriptions, the conduct, usability and interpretation of reviews are restricted and therefore, require action by trialists, systematic reviewers, peer reviewers and editors. PMID:26576811

Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials

PubMed Central

Briel, Matthias; Christ-Crain, Mirjam; Bonnema, Steen J; Connell, John; Cooper, David S; Bucher, Heiner C; Müller-Brand, Jan; Müller, Beat

2007-01-01

Objective To determine the effect of adjunctive antithyroid drugs on the risk of treatment failure, hypothyroidism, and adverse events after radioiodine treatment. Design Meta-analysis. Data sources 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. Results 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. Conclusions 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. PMID:17309884

Clinical applications of cell-based approaches in alveolar bone augmentation: a systematic review.

PubMed

Shanbhag, Siddharth; Shanbhag, Vivek

2015-01-01

Cell-based approaches, utilizing adult mesenchymal stem cells (MSCs), are reported to overcome the limitations of conventional bone augmentation procedures. The study aims to systematically review the available evidence on the characteristics and clinical effectiveness of cell-based ridge augmentation, socket preservation, and sinus-floor augmentation, compared to current evidence-based methods in human adult patients. MEDLINE, EMBASE, and CENTRAL databases were searched for related literature. Both observational and experimental studies reporting outcomes of "tissue engineered" or "cell-based" augmentation in ≥5 adult patients alone, or in comparison with non-cell-based (conventional) augmentation methods, were eligible for inclusion. Primary outcome was histomorphometric analysis of new bone formation. Effectiveness of cell-based augmentation was evaluated based on outcomes of controlled studies. Twenty-seven eligible studies were identified. Of these, 15 included a control group (8 randomized controlled trials [RCTs]), and were judged to be at a moderate-to-high risk of bias. Most studies reported the combined use of cultured autologous MSCs with an osteoconductive bone substitute (BS) scaffold. Iliac bone marrow and mandibular periosteum were frequently reported sources of MSCs. In vitro culture of MSCs took between 12 days and 1.5 months. A range of autogenous, allogeneic, xenogeneic, and alloplastic scaffolds was identified. Bovine bone mineral scaffold was frequently reported with favorable outcomes, while polylactic-polyglycolic acid copolymer (PLGA) scaffold resulted in graft failure in three studies. The combination of MSCs and BS resulted in outcomes similar to autogenous bone (AB) and BS. Three RCTs and one controlled trial reported significantly greater bone formation in cell-based than conventionally grafted sites after 3 to 8 months. Based on limited controlled evidence at a moderate-to-high risk of bias, cell-based approaches are comparable, if not superior, to current evidence-based bone grafting methods, with a significant advantage of avoiding AB harvesting. Future clinical trials should additionally evaluate patient-based outcomes and the time-/cost-effectiveness of these approaches. © 2013 Wiley Periodicals, Inc.

Stability of Special Education Eligibility from Kindergarten to Third Grade: Are There Variables from Fall of Kindergarten That Predict Later Classification Status?

ERIC Educational Resources Information Center

Flynn, Kylie Shawn

2012-01-01

This study examined students' movement in and out of special education and predictors for later special education placement. The sample ( N = 556) came from a response to intervention (RTI) study, specifically, a cluster-randomized control field trial that undertook the development and study of a hybrid Tier 1 (classroom instruction) and Tier 2…

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

The Efficacy of Guanxinning Injection in Treating Angina Pectoris: Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Jia, Yongliang; Leung, Siu-wai; Lee, Ming-Yuen; Cui, Guozhen; Huang, Xiaohui; Pan, Fongha

2013-01-01

Objective. The randomized controlled trials (RCTs) on Guanxinning injection (GXN) in treating angina pectoris were published only in Chinese and have not been systematically reviewed. This study aims to provide a PRISMA-compliant and internationally accessible systematic review to evaluate the efficacy of GXN in treating angina pectoris. Methods. The RCTs were included according to prespecified eligibility criteria. Meta-analysis was performed to evaluate the symptomatic (SYMPTOMS) and electrocardiographic (ECG) improvements after treatment. Odds ratios (ORs) were used to measure effect sizes. Subgroup analysis, sensitivity analysis, and metaregression were conducted to evaluate the robustness of the results. Results. Sixty-five RCTs published between 2002 and 2012 with 6064 participants were included. Overall ORs comparing GXN with other drugs were 3.32 (95% CI: [2.72, 4.04]) in SYMPTOMS and 2.59 (95% CI: [2.14, 3.15]) in ECG. Subgroup analysis, sensitivity analysis, and metaregression found no statistically significant dependence of overall ORs upon specific study characteristics. Conclusion. This meta-analysis of eligible RCTs provides evidence that GXN is effective in treating angina pectoris. This evidence warrants further RCTs of higher quality, longer follow-up periods, larger sample sizes, and multicentres/multicountries for more extensive subgroup, sensitivity, and metaregression analyses. PMID:23634167

CONCEPTT: Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial: A multi-center, multi-national, randomized controlled trial - Study protocol.

PubMed

Feig, Denice S; Asztalos, Elizabeth; Corcoy, Rosa; De Leiva, Alberto; Donovan, Lois; Hod, Moshe; Jovanovic, Lois; Keely, Erin; Kollman, Craig; McManus, Ruth; Murphy, Kellie; Ruedy, Katrina; Sanchez, J Johanna; Tomlinson, George; Murphy, Helen R

2016-07-18

Women with type 1 diabetes strive for optimal glycemic control before and during pregnancy to avoid adverse obstetric and perinatal outcomes. For most women, optimal glycemic control is challenging to achieve and maintain. The aim of this study is to determine whether the use of real-time continuous glucose monitoring (RT-CGM) will improve glycemic control in women with type 1 diabetes who are pregnant or planning pregnancy. A multi-center, open label, randomized, controlled trial of women with type 1 diabetes who are either planning pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to ≤ 86 mmol/mol) or are in early pregnancy (<13 weeks 6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to ≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible women will wear a CGM which does not display the glucose result for 6 days during the run-in phase. To be eligible for randomization, a minimum of 4 HGM measurements per day and a minimum of 96 hours total with 24 hours overnight (11 pm-7 am) of CGM glucose values are required. Those meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women will be recruited (110 planning pregnancy, 214 pregnant). This takes into account 15 and 20 % attrition rates for the planning pregnancy and pregnant cohorts and will detect a clinically relevant 0.5 % difference between groups at 90 % power with 5 % significance. Randomization will stratify for type of insulin treatment (pump or multiple daily injections) and baseline HbA1c. Analyses will be performed according to intention to treat. The primary outcome is the change in glycemic control as measured by HbA1c from baseline to 24 weeks or conception in women planning pregnancy, and from baseline to 34 weeks gestation during pregnancy. Secondary outcomes include maternal hypoglycemia, CGM time in, above and below target (3.5-7.8 mmol/l), glucose variability measures, maternal and neonatal outcomes. This will be the first international multicenter randomized controlled trial to evaluate the impact of RT- CGM before and during pregnancy in women with type 1 diabetes. ClinicalTrials.gov Identifier: NCT01788527 Registration Date: December 19, 2012.

The Clinical Effects of Aromatherapy Massage on Reducing Pain for the Cancer Patients: Meta-Analysis of Randomized Controlled Trials

PubMed Central

Chen, Ting-Hao; Tung, Tao-Hsin; Chen, Pei-Shih; Wang, Shu-Hui; Chao, Chuang-Min; Hsiung, Nan-Hsing; Chi, Ching-Chi

2016-01-01

Purpose. Aromatherapy massage is an alternative treatment in reducing the pain of the cancer patients. This study was to investigate whether aromatherapy massage could improve the pain of the cancer patients. Methods. We searched PubMed and Cochrane Library for relevant randomized controlled trials without language limitations between 1 January 1990 and 31 July 2015 with a priori defined inclusion and exclusion criteria. The search terms included aromatherapy, essential oil, pain, ache, cancer, tumor, and carcinoma. There were 7 studies which met the selection criteria and 3 studies were eventually included among 63 eligible publications. Results. This meta-analysis included three randomized controlled trials with a total of 278 participants (135 participants in the massage with essential oil group and 143 participants in the control (usual care) group). Compared with the control group, the massage with essential oil group had nonsignificant effect on reducing the pain (standardized mean difference = 0.01; 95% CI [−0.23,0.24]). Conclusion. Aromatherapy massage does not appear to reduce pain of the cancer patients. Further rigorous studies should be conducted with more objective measures. PMID:26884799

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.

Effect of providing free glasses on children’s educational outcomes in China: cluster randomized controlled trial

PubMed Central

Yi, Hongmei; Pang, Xiaopeng; Shi, Yaojiang; Chen, Qianyun; Meltzer, Mirjam E; le Cessie, Saskia; He, Mingguang; Rozelle, Scott; Liu, Yizhi

2014-01-01

Objective To assess the effect of provision of free glasses on academic performance in rural Chinese children with myopia. Design Cluster randomized, investigator masked, controlled trial. Setting 252 primary schools in two prefectures in western China, 2012-13. Participants 3177 of 19 934 children in fourth and fifth grades (mean age 10.5 years) with visual acuity <6/12 in either eye without glasses correctable to >6/12 with glasses. 3052 (96.0%) completed the study. Interventions Children were randomized by school (84 schools per arm) to one of three interventions at the beginning of the school year: prescription for glasses only (control group), vouchers for free glasses at a local facility, or free glasses provided in class. Main outcome measures Spectacle wear at endline examination and end of year score on a specially designed mathematics test, adjusted for baseline score and expressed in standard deviations. Results Among 3177 eligible children, 1036 (32.6%) were randomized to control, 988 (31.1%) to vouchers, and 1153 (36.3%) to free glasses in class. All eligible children would benefit from glasses, but only 15% wore them at baseline. At closeout glasses wear was 41% (observed) and 68% (self reported) in the free glasses group, and 26% (observed) and 37% (self reported) in the controls. Effect on test score was 0.11 SD (95% confidence interval 0.01 to 0.21) when the free glasses group was compared with the control group. The adjusted effect of providing free glasses (0.10, 0.002 to 0.19) was greater than parental education (0.03, −0.04 to 0.09) or family wealth (0.01, −0.06 to 0.08). This difference between groups was significant, but was smaller than the prespecified 0.20 SD difference that the study was powered to detect. Conclusions The provision of free glasses to Chinese children with myopia improves children’s performance on mathematics testing to a statistically significant degree, despite imperfect compliance, although the observed difference between groups was smaller than the study was originally designed to detect. Myopia is common and rarely corrected in this setting. Trial Registration Current Controlled Trials ISRCTN03252665. PMID:25249453

Calcium supplementation for the prevention of colorectal adenomas: A systematic review and meta-analysis of randomized controlled trials

PubMed Central

Bonovas, Stefanos; Fiorino, Gionata; Lytras, Theodore; Malesci, Alberto; Danese, Silvio

2016-01-01

AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas. METHODS: We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or “high-risk” adenomas), and rated each trial’s risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE. RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random-effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence). CONCLUSION: Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted. PMID:27182169

Effect of tree nuts on metabolic syndrome criteria: a systematic review and meta-analysis of randomised controlled trials

PubMed Central

Blanco Mejia, Sonia; Kendall, Cyril W C; Viguiliouk, Effie; Augustin, Livia S; Ha, Vanessa; Cozma, Adrian I; Mirrahimi, Arash; Maroleanu, Adriana; Chiavaroli, Laura; Leiter, Lawrence A; de Souza, Russell J; Jenkins, David J A; Sievenpiper, John L

2014-01-01

Objective To provide a broader evidence summary to inform dietary guidelines of the effect of tree nuts on criteria of the metabolic syndrome (MetS). Design We conducted a systematic review and meta-analysis of the effect of tree nuts on criteria of the MetS. Data sources We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library (through 4 April 2014). Eligibility criteria for selecting studies We included relevant randomised controlled trials (RCTs) of ≥3 weeks reporting at least one criterion of the MetS. Data extraction Two or more independent reviewers extracted all relevant data. Data were pooled using the generic inverse variance method using random effects models and expressed as mean differences (MD) with 95% CIs. Heterogeneity was assessed by the Cochran Q statistic and quantified by the I2 statistic. Study quality and risk of bias were assessed. Results Eligibility criteria were met by 49 RCTs including 2226 participants who were otherwise healthy or had dyslipidaemia, MetS or type 2 diabetes mellitus. Tree nut interventions lowered triglycerides (MD=−0.06 mmol/L (95% CI −0.09 to −0.03 mmol/L)) and fasting blood glucose (MD=−0.08 mmol/L (95% CI −0.16 to −0.01 mmol/L)) compared with control diet interventions. There was no effect on waist circumference, high-density lipoprotein cholesterol or blood pressure with the direction of effect favouring tree nuts for waist circumference. There was evidence of significant unexplained heterogeneity in all analyses (p<0.05). Conclusions Pooled analyses show a MetS benefit of tree nuts through modest decreases in triglycerides and fasting blood glucose with no adverse effects on other criteria across nut types. As our conclusions are limited by the short duration and poor quality of the majority of trials, as well as significant unexplained between-study heterogeneity, there remains a need for larger, longer, high-quality trials. Trial registration number NCT01630980. PMID:25074070

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.

Motivational interviewing for improving recovery after stroke.

PubMed

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

2015-06-03

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

Managing Injuries of the Neck Trial (MINT): design of a randomised controlled trial of treatments for whiplash associated disorders

PubMed Central

Lamb, Sarah E; Gates, Simon; Underwood, Martin R; Cooke, Matthew W; Ashby, Deborah; Szczepura, Ala; Williams, Mark A; Williamson, Esther M; Withers, Emma J; Mt Isa, Shahrul; Gumber, Anil

2007-01-01

Background A substantial proportion of patients with whiplash injuries develop chronic symptoms. However, the best treatment of acute injuries to prevent long-term problems is uncertain. A stepped care treatment pathway has been proposed, in which patients are given advice and education at their initial visit to the emergency department (ED), followed by review at three weeks and physiotherapy for those with persisting symptoms. MINT is a two-stage randomised controlled trial to evaluate two components of such a pathway: 1. use of The Whiplash Book versus usual advice when patients first attend the emergency department; 2. referral to physiotherapy versus reinforcement of advice for patients with continuing symptoms at three weeks. Methods Evaluation of the Whiplash Book versus usual advice uses a cluster randomised design in emergency departments of eight NHS Trusts. Eligible patients are identified by clinicians in participating emergency departments and are sent a study questionnaire within a week of their ED attendance. Three thousand participants will be included. Patients with persisting symptoms three weeks after their ED attendance are eligible to join an individually randomised study of physiotherapy versus reinforcement of the advice given in ED. Six hundred participants will be randomised. Follow-up is at 4, 8 and 12 months after their ED attendance. Primary outcome is the Neck Disability Index (NDI), and secondary outcomes include quality of life and time to return to work and normal activities. An economic evaluation is being carried out. Conclusion This paper describes the protocol and operational aspects of a complex intervention trial based in NHS emergency and physiotherapy departments, evaluating two components of a stepped-care approach to the treatment of whiplash injuries. The trial uses two randomisations, with the first stage being cluster randomised and the second individually randomised. PMID:17257408

Impact of e-learning on nurses' and student nurses knowledge, skills, and satisfaction: a systematic review and meta-analysis.

PubMed

Lahti, Mari; Hätönen, Heli; Välimäki, Maritta

2014-01-01

To review the impact of e-learning on nurses' and nursing student's knowledge, skills and satisfaction related to e-learning. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) to assess the impact of e-learning on nurses' and nursing student's knowledge, skills and satisfaction. Electronic databases including MEDLINE (1948-2010), CINAHL (1981-2010), Psychinfo (1967-2010) and Eric (1966-2010) were searched in May 2010 and again in December 2010. All RCT studies evaluating the effectiveness of e-learning and differentiating between traditional learning methods among nurses were included. Data was extracted related to the purpose of the trial, sample, measurements used, index test results and reference standard. An extraction tool developed for Cochrane reviews was used. Methodological quality of eligible trials was assessed. 11 trials were eligible for inclusion in the analysis. We identified 11 randomized controlled trials including a total of 2491 nurses and student nurses'. First, the random effect size for four studies showed some improvement associated with e-learning compared to traditional techniques on knowledge. However, the difference was not statistically significant (p=0.39, MD 0.44, 95% CI -0.57 to 1.46). Second, one study reported a slight impact on e-learning on skills, but the difference was not statistically significant, either (p=0.13, MD 0.03, 95% CI -0.09 to 0.69). And third, no results on nurses or student nurses' satisfaction could be reported as the statistical data from three possible studies were not available. Overall, there was no statistical difference between groups in e-learning and traditional learning relating to nurses' or student nurses' knowledge, skills and satisfaction. E-learning can, however, offer an alternative method of education. In future, more studies following the CONSORT and QUOROM statements are needed to evaluate the effects of these interventions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pain education to prevent chronic low back pain: a study protocol for a randomised controlled trial

PubMed Central

Traeger, Adrian C; Moseley, G Lorimer; Hübscher, Markus; Lee, Hopin; Skinner, Ian W; Nicholas, Michael K; Henschke, Nicholas; Refshauge, Kathryn M; Blyth, Fiona M; Main, Chris J; Hush, Julia M; Pearce, Garry; McAuley, James H

2014-01-01

Introduction Low back pain (LBP) is the leading cause of disability worldwide. Of those patients who present to primary care with acute LBP, 40% continue to report symptoms 3 months later and develop chronic LBP. Although it is possible to identify these patients early, effective interventions to improve their outcomes are not available. This double-blind (participant/outcome assessor) randomised controlled trial will investigate the efficacy of a brief educational approach to prevent chronic LBP in ‘at-risk’ individuals. Methods/analysis Participants will be recruited from primary care practices in the Sydney metropolitan area. To be eligible for inclusion participants will be aged 18–75 years, with acute LBP (<4 weeks’ duration) preceded by at least a 1 month pain-free period and at-risk of developing chronic LBP. Potential participants with chronic spinal pain and those with suspected serious spinal pathology will be excluded. Eligible participants who agree to take part will be randomly allocated to receive 2×1 h sessions of pain biology education or 2×1 h sessions of sham education from a specially trained study physiotherapist. The study requires 101 participants per group to detect a 1-point difference in pain intensity 3 months after pain onset. Secondary outcomes include the incidence of chronic LBP, disability, pain intensity, depression, healthcare utilisation, pain attitudes and beliefs, global recovery and recurrence and are measured at 1 week post-intervention, and at 3, 6 and 12 months post LBP onset. Ethics/dissemination Ethical approval was obtained from the University of New South Wales Human Ethics Committee in June 2013 (ref number HC12664). Outcomes will be disseminated through publication in peer-reviewed journals and presentations at international conference meetings. Trial registration number https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612001180808 PMID:24889854

Preladenant as an Adjunctive Therapy With Levodopa in Parkinson Disease: Two Randomized Clinical Trials and Lessons Learned.

PubMed

Hauser, Robert A; Stocchi, Fabrizio; Rascol, Olivier; Huyck, Susan B; Capece, Rachel; Ho, Tony W; Sklar, Peter; Lines, Christopher; Michelson, David; Hewitt, David

2015-12-01

Preladenant is an adenosine 2A receptor antagonist that reduced "off" time in a placebo-controlled phase 2b trial in patients with Parkinson disease (PD). We sought to confirm its efficacy in phase 3 trials. To evaluate preladenant as an adjunct to levodopa in patients with PD and motor fluctuations. Two 12-week, phase 3, randomized, placebo-controlled, double-blind trials performed from July 15, 2010, to April 16, 2013. The setting included neurology clinics, clinical research centers, and hospitals in the Americas, the European Union, Eastern Europe, India, and South Africa. Participants included patients with moderate to severe PD taking levodopa who were experiencing motor fluctuations. In trial 1, a total of 778 eligible patients were randomized to the addition of preladenant (2 mg, 5 mg, or 10 mg twice daily), placebo, or rasagiline mesylate (1 mg/d) in a 1:1:1:1:1 ratio. In trial 2, a total of 476 eligible patients were randomized to the addition of preladenant (2 mg or 5 mg twice daily) or placebo in a 1:1:1 ratio. The primary outcome measure was change in off time from baseline to week 12. In trial 1, neither preladenant nor rasagiline was superior to placebo in reducing off time from baseline to week 12. The differences vs placebo were -0.10 hour (95% CI, -0.69 to 0.46 hour) for preladenant 2 mg twice daily, -0.20 hour (95% CI, -0.75 to 0.41 hour) for preladenant 5 mg twice daily, -0.00 hour (95% CI, -0.62 to 0.53 hour) for preladenant 10 mg twice daily, and -0.30 hour (95% CI, -0.90 to 0.26 hour) for rasagiline mesylate 1 mg/d. In trial 2, preladenant was not superior to placebo in reducing off time from baseline to week 12. The differences vs placebo were -0.20 hour (95% CI, -0.72 to 0.35 hour) for preladenant 2 mg twice daily and -0.30 hour (95% CI, -0.86 to 0.21 hour) for preladenant 5 mg twice daily. Preladenant was well tolerated, with the most common adverse event that showed an increase over placebo in both trials being constipation (6%-8% for preladenant vs 1%-3% for placebo). In these phase 3 trials, preladenant did not significantly reduce off time compared with placebo. That the active control rasagiline also failed to demonstrate a significant reduction in off time suggests that issues of study design or conduct may have affected these trials. clinicaltrials.gov Identifier: NCT01155466 and NCT01227265.

The feasibility and acceptability of trial procedures for a pragmatic randomised controlled trial of a structured physical activity intervention for people diagnosed with colorectal cancer: findings from a pilot trial of cardiac rehabilitation versus usual care (no rehabilitation) with an embedded qualitative study.

PubMed

Hubbard, Gill; O'Carroll, Ronan; Munro, Julie; Mutrie, Nanette; Haw, Sally; Mason, Helen; Treweek, Shaun

2016-01-01

Pilot and feasibility work is conducted to evaluate the operational feasibility and acceptability of the intervention itself and the feasibility and acceptability of a trials' protocol design. The Cardiac Rehabilitation In Bowel cancer (CRIB) study was a pilot randomised controlled trial (RCT) of cardiac rehabilitation versus usual care (no rehabilitation) for post-surgical colorectal cancer patients. A key aim of the pilot trial was to test the feasibility and acceptability of the protocol design. A pilot RCT with embedded qualitative work was conducted in three sites. Participants were randomly allocated to cardiac rehabilitation or usual care groups. Outcomes used to assess the feasibility and acceptability of key trial parameters were screening, eligibility, consent, randomisation, adverse events, retention, completion, missing data, and intervention adherence rates. Colorectal patients' and clinicians' perceptions and experiences of the main trial procedures were explored by interview. Quantitative study. Three sites were involved. Screening, eligibility, consent, and retention rates were 79 % (156/198), 67 % (133/198), 31 % (41/133), and 93 % (38/41), respectively. Questionnaire completion rates were 97.5 % (40/41), 75 % (31/41), and 61 % (25/41) at baseline, follow-up 1, and follow-up 2, respectively. Sixty-nine percent (40) of accelerometer datasets were collected from participants; 31 % (20) were removed for not meeting wear-time validation. Qualitative study: Thirty-eight patients and eight clinicians participated. Key themes were benefits for people with colorectal cancer attending cardiac rehabilitation, barriers for people with colorectal cancer attending cardiac rehabilitation, generic versus disease-specific rehabilitation, key concerns about including people with cancer in cardiac rehabilitation, and barriers to involvement in a study about cardiac rehabilitation. The study highlights where threats to internal and external validity are likely to arise in any future studies of similar structured physical activity interventions for colorectal cancer patients using similar methods being conducted in similar contexts. This study shows that there is likely to be potential recruitment bias and potential imprecision due to sub-optimal completion of outcome measures, missing data, and sub-optimal intervention adherence. Hence, strategies to manage these risks should be developed to stack the odds in favour of conducting successful future trials. ISRCTN63510637.

What can qualitative research do for randomised controlled trials? A systematic mapping review

PubMed Central

O'Cathain, A; Thomas, K J; Drabble, S J; Rudolph, A; Hewison, J

2013-01-01

Objective To develop an empirically based framework of the aspects of randomised controlled trials addressed by qualitative research. Design Systematic mapping review of qualitative research undertaken with randomised controlled trials and published in peer-reviewed journals. Data sources MEDLINE, PreMEDLINE, EMBASE, the Cochrane Library, Health Technology Assessment, PsycINFO, CINAHL, British Nursing Index, Social Sciences Citation Index and ASSIA. Eligibility criteria Articles reporting qualitative research undertaken with trials published between 2008 and September 2010; health research, reported in English. Results 296 articles met the inclusion criteria. Articles focused on 22 aspects of the trial within five broad categories. Some articles 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, process 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 target condition for the trial (9%, 33/356). A minority of the qualitative research was undertaken at the pretrial stage (28%, 82/296). The value of the qualitative research to the trial itself was not always made explicit within the articles. The potential value included optimising the intervention and trial conduct, facilitating interpretation of the trial findings, helping trialists to be sensitive to the human beings involved in trials, and saving money by steering researchers towards interventions more likely to be effective in future trials. Conclusions A large amount of qualitative research undertaken with specific trials has been published, addressing a wide range of aspects of trials, with the potential to improve the endeavour of generating evidence of effectiveness of health interventions. Researchers can increase the impact of this work on trials by undertaking more of it at the pretrial stage and being explicit within their articles about the learning for trials and evidence-based practice. PMID:23794542

Comparing ICD9-encoded diagnoses and NLP-processed discharge summaries for clinical trials pre-screening: a case study.

PubMed

Li, Li; Chase, Herbert S; Patel, Chintan O; Friedman, Carol; Weng, Chunhua

2008-11-06

The prevalence of electronic medical record (EMR) systems has made mass-screening for clinical trials viable through secondary uses of clinical data, which often exist in both structured and free text formats. The tradeoffs of using information in either data format for clinical trials screening are understudied. This paper compares the results of clinical trial eligibility queries over ICD9-encoded diagnoses and NLP-processed textual discharge summaries. The strengths and weaknesses of both data sources are summarized along the following dimensions: information completeness, expressiveness, code granularity, and accuracy of temporal information. We conclude that NLP-processed patient reports supplement important information for eligibility screening and should be used in combination with structured data.

Transcutaneous electrical nerve stimulation for acute pain.

PubMed

Johnson, Mark I; Paley, Carole A; Howe, Tracey E; Sluka, Kathleen A

2015-06-15

This is a second update of a Cochrane Review originally published in Issue 2, 2009. Transcutaneous Electrical Nerve Stimulation (TENS) is a non-pharmacological agent, based on delivering low voltage electrical currents to the skin. TENS is used by people to treat a variety of pain conditions. To assess the analgesic effectiveness of TENS, as a sole treatment, for acute pain in adults. We searched the following databases up to 3 December 2014: the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE; EMBASE; CINAHL; and AMED. We also checked the reference lists of included trials. We included randomised controlled trials (RCTs) of adults with acute pain (< 12 weeks) if they examined TENS given as a sole treatment and assessed pain with subjective pain scales. Trials were eligible if they compared TENS to placebo TENS, no treatment controls, pharmacological interventions or non-pharmacological interventions. We excluded trials on experimental pain, case reports, clinical observations, letters, abstracts or reviews. Also we excluded trials investigating the effect of TENS on pain during childbirth (labour), primary dysmenorrhoea or dental procedures. Studies where TENS was given with another treatment as part of the formal trial design were excluded. We did not restrict any articles based on language of publication. Two review authors independently assessed study eligibility and carried out study selection, data extraction, 'Risk of bias' assessment and analyses of data. We extracted data on the following: types of participants and pain condition, trial design and methods, treatment parameters, adverse effects, and outcome measures. We contacted trial authors for additional information if necessary. We included 12 trials in the original review (2009) and included no further trials in the first update (2011). An additional seven new trials met the inclusion criteria in this second update. In total, we included 19 RCTs involving 1346 participants at entry, with 11 trials awaiting classification either because the full text was unavailable or information in the full text failed to clarify eligibility. We excluded most trials because TENS was given in combination with another treatment as part of the formal study design or TENS was not delivered using appropriate TENS technique. The types of acute pain included in this Cochrane Review were procedural pain, e.g. cervical laser treatment, venepuncture, screening flexible sigmoidoscopy and non-procedural pain, e.g. postpartum uterine contractions and rib fractures. We pooled data for pain intensity for six trials (seven comparisons) comparing TENS with placebo but the I(2) statistic suggested substantial heterogeneity. Mean difference (MD) with 95% confidence intervals (CIs) on a visual analogue scale (VAS, 100 mm) was -24.62 mm (95% CI -31.79 to -17.46) in favour of TENS. Data for the proportion of participants achieving ≥ 50% reduction in pain was pooled for four trials (seven comparisons) and relative risk was 3.91 (95% CI 2.42 to 6.32) in favour of TENS over placebo. We pooled data for pain intensity from five trials (seven comparisons) but the I(2) statistic suggested considerable heterogeneity. MD was -19.05 mm (95% CI -27.30 to -10.79) in favour of TENS using a random-effects model. It was not possible to pool other data. There was a high risk of bias associated with inadequate sample sizes in treatment arms and unsuccessful blinding of treatment interventions. Seven trials reported minor adverse effects, such as mild erythema and itching underneath the electrodes and participants disliking TENS sensation. This Cochrane Review update includes seven new trials, in addition to the 12 trials reviewed in the first update in 2011. The analysis provides tentative evidence that TENS reduces pain intensity over and above that seen with placebo (no current) TENS when administered as a stand-alone treatment for acute pain in adults. The high risk of bias associated with inadequate sample sizes in treatment arms and unsuccessful blinding of treatment interventions makes definitive conclusions impossible. There was incomplete reporting of treatment in many reports making replication of trials impossible.

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.

Ensuring Quality in AFRINEST and SATT

PubMed Central

2013-01-01

Background: Three randomized open-label clinical trials [Simplified Antibiotic Therapy Trial (SATT) Bangladesh, SATT Pakistan and African Neonatal Sepsis Trial (AFRINEST)] were developed to test the equivalence of simplified antibiotic regimens compared with the standard regimen of 7 days of parenteral antibiotics. These trials were originally conceived and designed separately; subsequently, significant efforts were made to develop and implement a common protocol and approach. Previous articles in this supplement briefly describe the specific quality control methods used in the individual trials; this article presents additional information about the systematic approaches used to minimize threats to validity and ensure quality across the trials. Methods: A critical component of quality control for AFRINEST and SATT was striving to eliminate variation in clinical assessments and decisions regarding eligibility, enrollment and treatment outcomes. Ensuring appropriate and consistent clinical judgment was accomplished through standardized approaches applied across the trials, including training, assessment of clinical skills and refresher training. Standardized monitoring procedures were also applied across the trials, including routine (day-to-day) internal monitoring of performance and adherence to protocols, systematic external monitoring by funding agencies and external monitoring by experienced, independent trial monitors. A group of independent experts (Technical Steering Committee/Technical Advisory Group) provided regular monitoring and technical oversight for the trials. Conclusions: Harmonization of AFRINEST and SATT have helped to ensure consistency and quality of implementation, both internally and across the trials as a whole, thereby minimizing potential threats to the validity of the trials’ results. PMID:23945575

Theory based interventions for caries related sugar intake in adults: systematic review.

PubMed

Al Rawahi, Said Hartih; Asimakopoulou, Koula; Newton, Jonathon Timothy

2017-07-25

Theories of behavior change are essential in the design of effective behaviour change strategies. No studies have assessed the effectiveness of interventions based on psychological theories to reduce sugar intake related to dental caries. The study assessed the effect of interventions based on Social Congition Models (SCMs) on sugar intake in adults, when compared with educational interventions or no intervention. A range of papers were considered: Systematic review Systematic Reviews with or without Meta Analyses; Randomised Controlled Trials; Controlled Clinical Trials and Before and after studies, of interventions based on Social Cognition Models aimed at dietary intake of sugar in adults. The Cochrane database including: Oral Health Group's Trials Register (2015), MEDLINE (from 1966 to September 2015), EMBASE (from 1980 to September 2015), PsycINFO (from 1966 to September 2015) were searched. No article met the full eligibility criteria for the current systematic review so no articles were included. There is a need for more clinical trials to assess the effectiveness of interventions based on psychological theory in reducing dietary sugar intake among adults. PROSPERO: CRD42015026357 .

Meta-Analysis of Individual Patient Data of Sodium Bicarbonate and Sodium Chloride for All-Cause Mortality After Coronary Angiography.

PubMed

Brown, Jeremiah R; Pearlman, Daniel M; Marshall, Emily J; Alam, Shama S; MacKenzie, Todd A; Recio-Mayoral, Alejandro; Gomes, Vitor O; Kim, Bokyung; Jensen, Lisette O; Mueller, Christian; Maioli, Mauro; Solomon, Richard J

2016-11-15

We sought to examine the relation between sodium bicarbonate prophylaxis for contrast-associated nephropathy (CAN) and mortality. We conducted an individual patient data meta-analysis from multiple randomized controlled trials. We obtained individual patient data sets for 7 of 10 eligible trials (2,292 of 2,764 participants). For the remaining 3 trials, time-to-event data were imputed based on follow-up periods described in their original reports. We included all trials that compared periprocedural intravenous sodium bicarbonate to periprocedural intravenous sodium chloride in patients undergoing coronary angiography or other intra-arterial interventions. Included trials were determined by consensus according to predefined eligibility criteria. The primary outcome was all-cause mortality hazard, defined as time from randomization to death. In 10 trials with a total of 2,764 participants, sodium bicarbonate was associated with lower mortality hazard than sodium chloride at 1 year (hazard ratio 0.61, 95% confidence interval [CI] 0.41 to 0.89, p = 0.011). Although periprocedural sodium bicarbonate was associated with a reduction in the incidence of CAN (relative risk 0.75, 95% CI 0.62 to 0.91, p = 0.003), there exists a statistically significant interaction between the effect on mortality and the occurrence of CAN (hazard ratio 5.65, 95% CI 3.58 to 8.92, p <0.001) for up to 1-year mortality. Periprocedural intravenous sodium bicarbonate seems to be associated with a reduction in long-term mortality in patients undergoing coronary angiography or other intra-arterial interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic Effect of Ultra-Staging Node Negative Colon Cancer without Adjuvant Chemotherapy: A Prospective National Cancer Institute Clinical Trial

PubMed Central

Protic, Mladjan; Stojadinovic, Alexander; Nissan, Aviram; Wainberg, Zev; Steele, Scott R.; Chen, David; Avital, Itzhak; Bilchik, Anton J.

2015-01-01

BACKGROUND We recently reported in a prospective randomized trial that ultra-staging of patients with colon cancer is associated with significantly improved disease-free survival (DFS) compared with conventional staging. That trial did not control for lymph node (LN) number or adjuvant chemotherapy use. STUDY DESIGN The current international prospective multi-center cooperative group trial (NCI Clinical Trial NCT00949312), “Ultra-staging in Early Colon Cancer” (UECC), evaluates whether the 12-LN quality measure and nodal ultra-staging impact DFS in patients not receiving adjuvant chemotherapy. Eligibility criteria include: a) biopsy-proven colon adenocarcinoma; b) absence of metastatic disease; c) > 12 LNs staged pathologically; d) pan-cytokeratin immunohistochemistry (IHC) of H&E-negative LNs; e) no adjuvant chemotherapy. RESULTS Of 442 patients screened, 203 patients were eligible. The majority of patients had intermediate grade (57.7%) and T3 tumors (64.9%). At a mean follow-up of 36.8±22.1 months (range 0–97 months), 94.3% remain disease-free. Recurrence was least likely in patients with ≥12, H&E negative, and IHC negative LNs (pN0i−): 2.6% vs.16.7% in the pN0i+ group (p<0.0001). CONCLUSIONS This is the first prospective report to demonstrate that patients with optimally staged node-negative colon cancer (≥12 LNs, pN0i−) are unlikely to benefit from adjuvant chemotherapy, as 97% remain disease free after primary tumor resection. Both surgical and pathological quality measures are imperative in the planning of clinical trials in non-metastatic colon cancer. PMID:26213360

Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials

PubMed Central

Ju, Woong; Oh, Seung-Won; Park, Sang Min; Koo, Bon-Kwon; Park, Byung-Joo

2013-01-01

Objective To assess the efficacy of vitamin and antioxidant supplements in the prevention of cardiovascular diseases. Design Meta-analysis of randomised controlled trials. Data sources and study selection PubMed, EMBASE, the Cochrane Library, Scopus, CINAHL, and ClinicalTrials.gov searched in June and November 2012. Two authors independently reviewed and selected eligible randomised controlled trials, based on predetermined selection criteria. Results Out of 2240 articles retrieved from databases and relevant bibliographies, 50 randomised controlled trials with 294 478 participants (156 663 in intervention groups and 137 815 in control groups) were included in the final analyses. In a fixed effect meta-analysis of the 50 trials, supplementation with vitamins and antioxidants was not associated with reductions in the risk of major cardiovascular events (relative risk 1.00, 95% confidence interval 0.98 to 1.02; I2=42%). Overall, there was no beneficial effect of these supplements in the subgroup meta-analyses by type of prevention, type of vitamins and antioxidants, type of cardiovascular outcomes, study design, methodological quality, duration of treatment, funding source, provider of supplements, type of control, number of participants in each trial, and supplements given singly or in combination with other supplements. Among the subgroup meta-analyses by type of cardiovascular outcomes, vitamin and antioxidant supplementation was associated with a marginally increased risk of angina pectoris, while low dose vitamin B6 supplementation was associated with a slightly decreased risk of major cardiovascular events. Those beneficial or harmful effects disappeared in subgroup meta-analysis of high quality randomised controlled trials within each category. Also, even though supplementation with vitamin B6 was associated with a decreased risk of cardiovascular death in high quality trials, and vitamin E supplementation with a decreased risk of myocardial infarction, those beneficial effects were seen only in randomised controlled trials in which the supplements were supplied by the pharmaceutical industry. Conclusion There is no evidence to support the use of vitamin and antioxidant supplements for prevention of cardiovascular diseases. PMID:23335472

Efficacy of the Pilates method for pain and disability in patients with chronic nonspecific low back pain: a systematic review with meta-analysis

PubMed Central

Miyamoto, Gisela C.; Costa, Leonardo O. P.; Cabral, Cristina M. N.

2013-01-01

Objective To systematically review the available evidence on the efficacy of the Pilates method in patients with chronic nonspecific low back pain. Method Searches were performed in MEDLINE, EMBASE, PEDro, SciELO, LILACS, CINAHL and CENTRAL in March 2013. Randomized controlled trials that tested the effectiveness of the Pilates method (against a nontreatment group, minimal intervention or other types of interventions) in adults with chronic low back pain were included regardless the language of publication. The outcome data were extracted from the eligible studies and were combined using a meta-analysis approach. Results The searches identified a total of 1,545 articles. From these, eight trials were considered eligible, and seven trials were combined in the meta-analysis. The comparison groups were as follows: Pilates versus other types of exercises (n=2 trials), and Pilates versus no treatment group or minimal intervention (n=4 trials) for short term pain; Pilates versus minimal intervention for short-term disability (n=4).We determined that Pilates was not better than other types of exercises for reducing pain intensity. However, Pilates was better than a minimal intervention for reducing short-term pain and disability (pain: pooled mean difference=1.6 points; 95% CI 1.4 to 1.8; disability: pooled mean difference=5.2 points; 95% CI 4.3 to 6.1). Conclusions Pilates was better than a minimal intervention for reducing pain and disability in patients with chronic low back pain. Pilates was not better than other types of exercise for short-term pain reduction. PMID:24346291

Efficacy of the Pilates method for pain and disability in patients with chronic nonspecific low back pain: a systematic review with meta-analysis.

PubMed

Miyamoto, Gisela C; Costa, Leonardo O P; Cabral, Cristina M N

2013-01-01

To systematically review the available evidence on the efficacy of the Pilates method in patients with chronic nonspecific low back pain. Searches were performed in MEDLINE, EMBASE, PEDro, SciELO, LILACS, CINAHL and CENTRAL in March 2013. Randomized controlled trials that tested the effectiveness of the Pilates method (against a nontreatment group, minimal intervention or other types of interventions) in adults with chronic low back pain were included regardless the language of publication. The outcome data were extracted from the eligible studies and were combined using a meta-analysis approach. The searches identified a total of 1,545 articles. From these, eight trials were considered eligible, and seven trials were combined in the meta-analysis. The comparison groups were as follows: Pilates versus other types of exercises (n=2 trials), and Pilates versus no treatment group or minimal intervention (n=4 trials) for short term pain; Pilates versus minimal intervention for short-term disability (n=4).We determined that Pilates was not better than other types of exercises for reducing pain intensity. However, Pilates was better than a minimal intervention for reducing short-term pain and disability (pain: pooled mean difference=1.6 points; 95% CI 1.4 to 1.8; disability: pooled mean difference=5.2 points; 95% CI 4.3 to 6.1). Pilates was better than a minimal intervention for reducing pain and disability in patients with chronic low back pain. Pilates was not better than other types of exercise for short-term pain reduction.

Staying well after depression: trial design and protocol.

PubMed

Williams, J Mark G; Russell, Ian T; Crane, Catherine; Russell, Daphne; Whitaker, Chris J; Duggan, Danielle S; Barnhofer, Thorsten; Fennell, Melanie J V; Crane, Rebecca; Silverton, Sarah

2010-03-19

Depression is often a chronic relapsing condition, with relapse rates of 50-80% in those who have been depressed before. This is particularly problematic for those who become suicidal when depressed since habitual recurrence of suicidal thoughts increases likelihood of further acute suicidal episodes. Therefore the question how to prevent relapse is of particular urgency in this group. This trial compares Mindfulness-Based Cognitive Therapy (MBCT), a novel form of treatment combining mindfulness meditation and cognitive therapy for depression, with both Cognitive Psycho-Education (CPE), an equally plausible cognitive treatment but without meditation, and treatment as usual (TAU). It will test whether MBCT reduces the risk of relapse in recurrently depressed patients and the incidence of suicidal symptoms in those with a history of suicidality who do relapse. It recruits participants, screens them by telephone for main inclusion and exclusion criteria and, if they are eligible, invites them to a pre-treatment session to assess eligibility in more detail. This trial allocates eligible participants at random between MBCT and TAU, CPE and TAU, and TAU alone in a ratio of 2:2:1, stratified by presence of suicidal ideation or behaviour and current anti-depressant use. We aim to recruit sufficient participants to allow for retention of 300 following attrition. We deliver both active treatments in groups meeting for two hours every week for eight weeks. We shall estimate effects on rates of relapse and suicidal symptoms over 12 months following treatment and assess clinical status immediately after treatment, and three, six, nine and twelve months thereafter. This will be the first trial of MBCT to investigate whether MCBT is effective in preventing relapse to depression when compared with a control psychological treatment of equal plausibility; and to explore the use of MBCT for the most severe recurrent depression--that in people who become suicidal when depressed.

What can we learn from trial decliners about improving recruitment? Qualitative study.

PubMed

Hughes-Morley, Adwoa; Young, Bridget; Hempel, Roelie J; Russell, Ian T; Waheed, Waquas; Bower, Peter

2016-10-12

Trials increasingly experience problems in recruiting participants. Understanding the causes of poor recruitment is critical to developing solutions. We interviewed people who had declined a trial of an innovative psychological therapy for depression (REFRAMED) about their response to the trial invitation, in order to understand their decision and identify ways to improve recruitment. Of 214 people who declined the trial, 35 (16 %) gave permission to be contacted about a qualitative study to explore their decision. Analysis of transcripts of semi-structured interviews was informed by grounded theory. We interviewed 20 informants: 14 women and six men, aged 18 to 77 years. Many interviewees had prior experience of research participation and positive views of the trial. Interviewees' decision making resembled a four-stage sequential process; in each stage they either decided not to participate in the trial or progressed to the next stage. In stage 1, interviewees assessed the invitation in the context of their experiences and attitudes; we term those who opted out at this stage 'prior decliners' as they had an established position of declining trials. In stage 2, interviewees assessed their own eligibility; those who judged themselves ineligible and opted out at this stage are termed 'self-excluders'. In stage 3, interviewees assessed their need for the trial therapy and potential to benefit; we term those who decided they did not need the trial therapy and opted out at this stage 'treatment decliners'. In stage 4, interviewees deliberated the benefits and costs of trial participation; those who opted out after judging that disadvantages outweighed advantages are termed 'trial decliners'. Across all stages, most individuals declined because they judged themselves ineligible or not in need of the trial therapy. While 'prior decliners' are unlikely to respond to any trial recruitment initiative, the factors leading others to decline are amenable to amelioration as they do not arise from a rejection of trials or a personal stance. To improve recruitment in similar trials, the most successful interventions are likely to address patients' assessments of their eligibility and their potential to benefit from the trial treatment, rather than reducing trial burden. International Standard Randomised Controlled Trial Number: ISRCTN85784627 . Registration date 10 August 2011.

Targets and self-management for the control of blood pressure in stroke and at risk groups (TASMIN-SR): protocol for a randomised controlled trial.

PubMed

O'Brien, Claire; Bray, Emma P; Bryan, Stirling; Greenfield, Sheila M; Haque, M Sayeed; Hobbs, F D Richard; Jones, Miren I; Jowett, Sue; Kaambwa, Billingsley; Little, Paul; Mant, Jonathan; Penaloza, Cristina; Schwartz, Claire; Shackleford, Helen; Varghese, Jinu; Williams, Bryan; McManus, Richard J

2013-03-23

Self-monitoring of hypertension with self-titration of antihypertensives (self-management) results in lower systolic blood pressure for at least one year. However, few people in high risk groups have been evaluated to date and previous work suggests a smaller effect size in these groups. This trial therefore aims to assess the added value of self-management in high risk groups over and above usual care. The targets and self-management for the control of blood pressure in stroke and at risk groups (TASMIN-SR) trial will be a pragmatic primary care based, unblinded, randomised controlled trial of self-management of blood pressure (BP) compared to usual care. Eligible patients will have a history of stroke, coronary heart disease, diabetes or chronic kidney disease and will be recruited from primary care. Participants will be individually randomised to either usual care or self-management. The primary outcome of the trial will be difference in office SBP between intervention and control groups at 12 months adjusted for baseline SBP and covariates. 540 patients will be sufficient to detect a difference in SBP between self-management and usual care of 5 mmHg with 90% power. Secondary outcomes will include self-efficacy, lifestyle behaviours, health-related quality of life and adverse events. An economic analysis will consider both within trial costs and a model extrapolating the results thereafter. A qualitative analysis will gain insights into patients' views, experiences and decision making processes. The results of the trial will be directly applicable to primary care in the UK. If successful, self-management of blood pressure in people with stroke and other high risk conditions would be applicable to many hundreds of thousands of individuals in the UK and beyond. ISRCTN87171227.

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

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.

Prevalence of Eligibility Criteria for the Systolic Blood Pressure Intervention Trial in US Adults Among Excluded Groups: Age <50 Years, Diabetes Mellitus, or a History of Stroke.

PubMed

Bress, Adam P; Tanner, Rikki M; Hess, Rachel; Gidding, Samuel S; Colantonio, Lisandro D; Shimbo, Daichi; Muntner, Paul

2016-07-12

Adults <50 years old, with diabetes mellitus, or a history of stroke were not enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). Estimating the size and characteristics of these excluded groups who meet the other SPRINT eligibility criteria may provide information on the potential impact of providers extending the SPRINT findings to these populations. We analyzed the National Health and Nutrition Examination Survey 2003-2012 (n=25 076) to estimate the percentage and characteristics of US adults ≥20 years in 3 populations (age <50 years, diabetes mellitus, or history of stroke) excluded from SPRINT who otherwise meet the trial eligibility criteria: age ≥50 years, systolic blood pressure (SBP) 130-180 mm Hg, high cardiovascular disease risk, and not having trial exclusion criteria. Overall, 1.0% (95% CI 0.8-1.3) of US adults age <50 years, 25.4% (95% CI 23.4-27.6) with diabetes mellitus, and 19.0% (95% CI 16.0-22.4) with history of stroke met the other SPRINT eligibility criteria. Among US adults with SBP ≥130 mm Hg, other SPRINT eligibility criteria were met by 7.5% (95% CI 6.1-9.2) of those age <50 years, 32.9% (95% CI 30.5-35.4) with diabetes mellitus, and 23.0% (95% CI 19.4-27.0) with history of stroke. Among US adults meeting the other SPRINT eligibility criteria, antihypertensive medication was being taken by 31.0% (95% CI 23.9-41.3) of those <50 years, 63.0% (95% CI 58.2-67.6) with diabetes mellitus, and 68.9% (95% CI 59.4-77.1) with a history of stroke. A substantial percentage of US adults with diabetes mellitus or history of stroke and a small percentage <50 years old meet the other SPRINT eligibility criteria. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

The Prevalence of Japanese Outpatients with Hypertension Who Meet the Definition of Treatment Resistant Hypertension and Are Eligible for Enrolment in Clinical Trials of Endovascular Ultrasound Renal Denervation.

PubMed

Okamura, Keisuke; Shirai, Kazuyuki; Okuda, Tetsu; Urata, Hidenori

2018-01-01

Objective A clinical trial (REQUIRE) was started to investigate the use of an ultrasound renal denervation system in the treatment of resistant hypertension (RHT). We analyzed the prevalence of patients who were eligible for inclusion in this cross-sectional study at the time of screening. Methods Nine-hundred ninety-nine consecutive hypertension (HT) patients who were treated in our hospital as outpatients were classified into the following categories: patients treated with at least 3 types of antihypertensive drugs including diuretic agents who were eligible for enrolment in SYMPLICITY HTN-Japan (SH-J) with an office systolic blood pressure (SBP) of ≥160 mmHg, who were ≤80 years of age, and an estimated glomerular filtration rate (eGFR) of ≥45 mL/min/1.73 m 2 (RHT-S); and patients who were treated similar medications and who were eligible for enrolment in REQUIRE, with an SBP of ≥150 mmHg, ≤75 years of age, and an eGFR of ≥40 mL/min/1.73 m 2 (RHT-R). We investigated the proportion of patients in each category. We also investigated HT patients (1,423 cases) who were enrolled in the Chikushi Anti-Hypertension Trial (CHAT), a research network that includes general practitioners. Results Eleven patients (1.1%) with RHT-S and 18 patients (1.8%) with RHT-R were identified. After the exclusion of patients with secondary HT and a diastolic blood pressure (DBP) of <90 mmHg (applied in REQUIRE), 5 patients (0.5%) with RHT-S and 4 patients (0.4%) with RHT-R remained. In the analysis of the CHAT study, only 2 (0.1%) patients with RHT-R remained. Conclusion The number of eligible patients in the REQUIRE trial was decreased, largely due to the strict age restriction and the new DBP limitation. The prevalence of eligible patients in REQUIRE was estimated to be approximately 0.5 to 0.8 times that in SH-J. Since patient enrollment will be difficult, drastic measures may be required to recruit eligible patients.

Self-monitoring of blood pressure in hypertension: A systematic review and individual patient data meta-analysis.

PubMed

Tucker, Katherine L; Sheppard, James P; Stevens, Richard; Bosworth, Hayden B; Bove, Alfred; Bray, Emma P; Earle, Kenneth; George, Johnson; Godwin, Marshall; Green, Beverly B; Hebert, Paul; Hobbs, F D Richard; Kantola, Ilkka; Kerry, Sally M; Leiva, Alfonso; Magid, David J; Mant, Jonathan; Margolis, Karen L; McKinstry, Brian; McLaughlin, Mary Ann; Omboni, Stefano; Ogedegbe, Olugbenga; Parati, Gianfranco; Qamar, Nashat; Tabaei, Bahman P; Varis, Juha; Verberk, Willem J; Wakefield, Bonnie J; McManus, Richard J

2017-09-01

Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may benefit most. This individual patient data (IPD) meta-analysis was performed to better understand the effectiveness of BP self-monitoring to lower BP and control hypertension. Medline, Embase, and the Cochrane Library were searched for randomised trials comparing self-monitoring to no self-monitoring in hypertensive patients (June 2016). Two reviewers independently assessed articles for eligibility and the authors of eligible trials were approached requesting IPD. Of 2,846 articles in the initial search, 36 were eligible. IPD were provided from 25 trials, including 1 unpublished study. Data for the primary outcomes-change in mean clinic or ambulatory BP and proportion controlled below target at 12 months-were available from 15/19 possible studies (7,138/8,292 [86%] of randomised participants). Overall, self-monitoring was associated with reduced clinic systolic blood pressure (sBP) compared to usual care at 12 months (-3.2 mmHg, [95% CI -4.9, -1.6 mmHg]). However, this effect was strongly influenced by the intensity of co-intervention ranging from no effect with self-monitoring alone (-1.0 mmHg [-3.3, 1.2]), to a 6.1 mmHg (-9.0, -3.2) reduction when monitoring was combined with intensive support. Self-monitoring was most effective in those with fewer antihypertensive medications and higher baseline sBP up to 170 mmHg. No differences in efficacy were seen by sex or by most comorbidities. Ambulatory BP data at 12 months were available from 4 trials (1,478 patients), which assessed self-monitoring with little or no co-intervention. There was no association between self-monitoring and either lower clinic or ambulatory sBP in this group (clinic -0.2 mmHg [-2.2, 1.8]; ambulatory 1.1 mmHg [-0.3, 2.5]). Results for diastolic blood pressure (dBP) were similar. The main limitation of this work was that significant heterogeneity remained. This was at least in part due to different inclusion criteria, self-monitoring regimes, and target BPs in included studies. Self-monitoring alone is not associated with lower BP or better control, but in conjunction with co-interventions (including systematic medication titration by doctors, pharmacists, or patients; education; or lifestyle counselling) leads to clinically significant BP reduction which persists for at least 12 months. The implementation of self-monitoring in hypertension should be accompanied by such co-interventions.

A Randomized Controlled Trial to Measure Spillover Effects of a Combined Water, Sanitation, and Handwashing Intervention in Rural Bangladesh.

PubMed

Benjamin-Chung, Jade; Amin, Nuhu; Ercumen, Ayse; Arnold, Benjamin F; Hubbard, Alan E; Unicomb, Leanne; Rahman, Mahbubur; Luby, Stephen P; Colford, John M

2018-03-27

Water, sanitation, and handwashing interventions may confer spillover effects on neighbors of intervention recipients by interrupting pathogen transmission. We measured geographically local spillovers in WASH Benefits, a cluster-randomized trial in rural Bangladesh, by comparing outcomes among neighbors of intervention vs. control participants. WASH Benefits randomly allocated geographically-defined clusters to a compound-level intervention (chlorinated drinking water, upgraded sanitation, and handwashing promotion) or control. From January to August 2015, in 180 clusters, we enrolled 1,799 neighboring children age-matched to trial participants that would have been eligible for WASH Benefits had they been conceived slightly earlier or later. After 28 months of intervention, we quantified fecal indicator bacteria in toy rinse and drinking water samples, measured soil-transmitted helminth infections, and recorded caregiver-reported diarrhea and respiratory illness. Neighbors' characteristics were balanced across arms. The prevalence of detectable E. coli in tubewell samples was lower for neighbors of intervention vs. control trial participants (prevalence ratio = 0.83; 0.73, 0.95). There was no difference in fecal indicator bacteria prevalence between arms for other environmental samples. Prevalence was similar in neighbors of intervention vs. control participants for soil-transmitted helminth infection, diarrhea, and respiratory illness. A compound-level water, sanitation, and handwashing intervention reduced neighbors' tubewell water contamination but did not impact neighboring children's health.

An randomized controlled trial of Post-it® notes did not increase postal response rates in older depressed participants.

PubMed

Lewis, Helen; Keding, Ada; Bosanquet, Katharine; Gilbody, Simon; Torgerson, David

2017-02-01

Our aim was to evaluate the effectiveness of a Post-it® note to increase response rates and shorten response times to a 4-month postal follow-up questionnaire sent to participants taking part in the Collaborative Care in Screen-Positive Elders (CASPER) trials. Our trial was a two-arm randomized controlled trial comparing response rates to questionnaires with a printed Post-it® note (intervention) and without (control), nested in multi centred randomized controlled trials of older people with varying levels of depressive symptoms; the CASPER + and CASPER Self Help for those At Risk of Depression (SHARD) trials. A total of 611 participants were eligible and randomized. The primary outcome was response rates, secondary outcomes were time to response and need for a reminder. Of 297 participants, 266 (89.6%) returned their 4-month questionnaire in the post-it note arm, compared with 282 of 314 participants (89.8%) in the control arm (OR = 0.97, 95% CI: 0.57, 1.65, P = 0.913). There were no statistically significant differences in time to respond or the need to be sent a reminder. Patients with a major depressive episode were more likely to return questionnaires with post-it notes (P of interaction = .019). There was no significant difference in response rates, time to response, or the need for a reminder between the intervention and control at 4-month follow up for older people with depressive symptoms. However, there was a significant interaction between the Post-it® note group and level of depression. © 2016 John Wiley & Sons, Ltd.

Impact of a Daily SMS Medication Reminder System on Tuberculosis Treatment Outcomes: A Randomized Controlled Trial.

PubMed

Mohammed, Shama; Glennerster, Rachel; Khan, Aamir J

2016-01-01

The rapid uptake of mobile phones in low and middle-income countries over the past decade has provided public health programs unprecedented access to patients. While programs have used text messages to improve medication adherence, there have been no high-powered trials evaluating their impact on tuberculosis treatment outcomes. To measure the impact of Zindagi SMS, a two-way SMS reminder system, on treatment success of people with drug-sensitive tuberculosis. We conducted a two-arm, parallel design, effectiveness randomized controlled trial in Karachi, Pakistan. Individual participants were randomized to either Zindagi SMS or the control group. Zindagi SMS sent daily SMS reminders to participants and asked them to respond through SMS or missed (unbilled) calls after taking their medication. Non-respondents were sent up to three reminders a day. Public and private sector tuberculosis clinics in Karachi, Pakistan. Newly-diagnosed patients with smear or bacteriologically positive pulmonary tuberculosis who were on treatment for less than two weeks; 15 years of age or older; reported having access to a mobile phone; and intended to live in Karachi throughout treatment were eligible to participate. We enrolled 2,207 participants, with 1,110 randomized to Zindagi SMS and 1,097 to the control group. The primary outcome was clinically recorded treatment success based upon intention-to-treat. We found no significant difference between the Zindagi SMS or control groups for treatment success (719 or 83% vs. 903 or 83%, respectively, p = 0·782). There was no significant program effect on self-reported medication adherence reported during unannounced visits during treatment. In this large-scale randomized controlled effectiveness trial of SMS medication reminders for tuberculosis treatment, we found no significant impact. The trial was registered with ClinicalTrials.gov, NCT01690754.

Veterinary homeopathy: systematic review of medical conditions studied by randomised trials controlled by other than placebo.

PubMed

Mathie, Robert T; Clausen, Jürgen

2015-09-15

No systematic review has previously been carried out on randomised controlled trials (RCTs) of veterinary homeopathy in which the control group was an intervention other than placebo (OTP). For eligible peer-reviewed RCTs, the objectives of this study were to assess the risk of bias (RoB) and to quantify the effect size of homeopathic intervention compared with an active comparator or with no treatment. Our systematic review approach complied fully with the PRISMA 2009 Checklist. Cochrane methods were applied to assess RoB and to derive effect size using standard meta-analysis methods. Based on a thorough and systematic literature search, the following key attributes of the published research were distinguished: individualised homeopathy (n = 1 RCT)/non-individualised homeopathy (n = 19); treatment (n = 14)/prophylaxis (n = 6); active controls (n = 18)/untreated controls (n = 2). The trials were highly diverse, representing 12 different medical conditions in 6 different species. No trial had sufficiently low RoB to be judged as reliable evidence: 16 of the 20 RCTs had high RoB; the remaining four had uncertain RoB in several domains of assessment. For three trials with uncertain RoB and without overt vested interest, it was inconclusive whether homeopathy combined with conventional intervention was more or was less effective than conventional intervention alone for modulation of immune response in calves, or in the prophylaxis of cattle tick or of diarrhoea in piglets. Due to the poor reliability of their data, OTP-controlled trials do not currently provide useful insight into the effectiveness of homeopathy in animals.

Effectiveness of policy to provide breastfeeding groups (BIG) for pregnant and breastfeeding mothers in primary care: cluster randomised controlled trial.

PubMed

Hoddinott, Pat; Britten, Jane; Prescott, Gordon J; Tappin, David; Ludbrook, Anne; Godden, David J

2009-01-30

To assess the clinical effectiveness and cost effectiveness of a policy to provide breastfeeding groups for pregnant and breastfeeding women. Cluster randomised controlled trial with prospective mixed method embedded case studies to evaluate implementation processes. Primary care in Scotland. Pregnant women, breastfeeding mothers, and babies registered with 14 of 66 eligible clusters of general practices (localities) in Scotland that routinely collect breastfeeding outcome data. Localities set up new breastfeeding groups to provide population coverage; control localities did not change group activity. any breast feeding at 6-8 weeks from routinely collected data for two pre-trial years and two trial years. any breast feeding at birth, 5-7 days, and 8-9 months; maternal satisfaction. Between 1 February 2005 and 31 January 2007, 9747 birth records existed for intervention localities and 9111 for control localities. The number of breastfeeding groups increased from 10 to 27 in intervention localities, where 1310 women attended, and remained at 10 groups in control localities. No significant differences in breastfeeding outcomes were found. Any breast feeding at 6-8 weeks declined from 27% to 26% in intervention localities and increased from 29% to 30% in control localities (P=0.08, adjusted for pre-trial rate). Any breast feeding at 6-8 weeks increased from 38% to 39% in localities not participating in the trial. Women who attended breastfeeding groups were older (P<0.001) than women initiating breast feeding who did not attend and had higher income (P=0.02) than women in the control localities who attended postnatal groups. The locality cost was pound13 400 (euro14 410; $20 144) a year. A policy for providing breastfeeding groups in relatively deprived areas of Scotland did not improve breastfeeding rates at 6-8 weeks. The costs of running groups would be similar to the costs of visiting women at home. Current Controlled Trials ISRCTN44857041.

Lifestyle interventions to reduce risk of diabetes among women with prior gestational diabetes mellitus.

PubMed

Chasan-Taber, Lisa

2015-01-01

While lifestyle interventions involving exercise and a healthy diet in high-risk adults have been found to reduce progression to type 2 diabetes by >50%, little attention has been given to the potential benefits of such strategies in women with a history of gestational diabetes mellitus (GDM). We conducted a literature search of PubMed for English language studies of randomized controlled trials of lifestyle interventions among women with a history of GDM. In total, nine studies were identified which fulfilled the eligibility criteria. The majority of randomized trials of lifestyle interventions in women with GDM have been limited to pilot or feasibility studies. However, preliminary findings suggest that such interventions can improve diabetes risk factors in women with a history of GDM. Larger, well-designed controlled randomized trials are needed to assess the effects of lifestyle interventions on preventing subsequent progression to type 2 diabetes among women with GDM. Copyright © 2014 Elsevier Ltd. All rights reserved.

National evaluation of strategies to reduce safety violations for working from heights in construction companies: results from a randomized controlled trial.

PubMed

van der Molen, Henk F; den Herder, Aalt; Warning, Jan; Frings-Dresen, Monique H W

2016-01-09

The objective of this study is to evaluate the effectiveness of a face-to-face strategy and a direct mail strategy on safety violations while working from heights among construction companies compared to a control condition. Construction companies with workers at risk for fall injuries were eligible for this three-armed randomized controlled trial. In total, 27 cities were randomly assigned to intervention groups-where eligible companies were given either a face-to-face guidance strategy or a direct mailing strategy with access to internet facilities-or to a control group. The primary outcomes were the number and type of safety violations recorded by labor inspectors after three months. A process evaluation for both strategies was performed to determine reach, program implementation, satisfaction, knowledge and perceived safety behavior. A cost analysis was performed to establish the financial costs for each intervention strategy. Analyses were done by intention to treat. In total, 41% (n = 88) of the companies eligible for the face-to-face intervention participated and 73% (n = 69) for direct mail. Intervention materials were delivered to 69 % (face-to-face group) and 100 % (direct mail group); completion of intervention activities within companies was low. Satisfaction, increase in knowledge, and safety behavior did not differ between the intervention groups. Costs for personal advice were 28% higher than for direct mail. Ultimately, nine intervention companies were captured in the 288 worksite measurements performed by the labor inspectorate. No statistical differences in mean number of safety violations (1.8-2.4) or penalties (72%-100%) were found between the intervention and control groups based on all worksite inspections. No conclusions about the effect of face-to-face and direct mail strategies on safety violations could be drawn due to the limited number of intervention companies captured in the primary outcome measurements. The costs for a face-to-face strategy are higher compared with a direct mail strategy. No difference in awareness and attitude for safe working was found between employers and workers between both strategies. NTR 4298 on 29-Nov-2013.

Effect of Transcutaneous Electric Nerve Stimulation on Pain after Total Knee Arthroplasty: A Blind Randomized Controlled Trial.

PubMed

Beckwée, David; Bautmans, Ivan; Lefeber, Nina; Lievens, Pierre; Scheerlinck, Thierry; Vaes, Peter

2018-02-01

Transcutaneous electric nerve stimulation (TENS) has proven to be effective for postsurgical pain relief. However, there is a lack of well-constructed clinical trials investigating the effect of TENS after total knee arthroplasty (TKA). In addition, previous investigations reported that low- and high-frequency TENSs produced analgesic tolerance after 4 or 5 days of treatment. The aim of this study is to explore the effect of burst TENS on pain during hospitalization after TKA and to investigate whether burst TENS produces analgesic tolerance after 4 or 5 days of treatment. This stratified, triple blind, randomized controlled trial was approved by the University Hospital Brussels. Sixty-eight subjects were screened for eligibility before surgery; 54 were found eligible and 53 were included in the analyses. Patients were allocated to either a burst TENS or sham burst TENS group. TENS was applied daily during continuous passive mobilization. Knee pain intensity, knee range of motion, and analgesic consumption were assessed daily. Patients received burst TENS ( N  = 25) or sham burst TENS ( N  = 28). No significant differences in knee pain intensity were found between the groups ( p  > 0.05). Within the TENS and the sham TENS groups, the difference in knee pain before and after treatment did not evolve over time ( p  > 0.05). This study found no effects of burst TENS compared with sham burst TENS on pain during hospitalization after TKA. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Intravenous magnesium for pediatric sickle cell vaso-occlusive crisis: methodological issues of a randomized controlled trial.

PubMed

Badaki-Makun, Oluwakemi; Scott, J Paul; Panepinto, Julie A; Casper, T Charles; Hillery, Cheryl A; Dean, J Michael; Brousseau, David C

2014-06-01

Multiple recent Sickle Cell Disease studies have been terminated due to poor enrollment. We developed methods to overcome past barriers and utilized these to study the efficacy and safety of intravenous magnesium for vaso-occlusive crisis (VOC). We describe the methods of the Intravenous Magnesium in Sickle Vaso-occlusive Crisis (MAGiC) trial and discuss methods used to overcome past barriers. MAGiC was a multi-center randomized double-blind placebo-controlled trial of intravenous magnesium versus normal saline for treatment of VOC. The study was a collaboration between Pediatric Hematologists and Emergency Physicians in the Pediatric Emergency Care Applied Research Network (PECARN). Eligible patients were randomized within 12 hours of receiving intravenous opioids in the Emergency Department (ED) and administered study medication every 8 hours. The primary outcome was hospital length of stay. Associated plasma studies elucidated magnesium's mechanism of action and the pathophysiology of VOC. Health-related quality of life was measured. Site-, protocol-, and patient-related barriers from prior studies were identified and addressed. Limited study staff availability, lack of collaboration with the ED, and difficulty obtaining consent were previously identified barriers. Leveraging PECARN resources, forging close collaborations between Sickle Cell Centers and EDs of participating sites, and approaching eligible patients for prior consent helped overcome these barriers. Participation in the PECARN network and establishment of collaborative arrangements between Sickle Cell Centers and their affiliated EDs are major innovative features of the MAGiC study that allowed improved subject capture. These methods could serve as a model for future studies of VOCs. © 2014 Wiley Periodicals, Inc.

The efficacy of treadmill training on balance dysfunction in individuals with chronic stroke: a systematic review.

PubMed

Tally, Zachary; Boetefuer, Laura; Kauk, Courtney; Perez, Gabriela; Schrand, Lorraine; Hoder, Jeffrey

2017-10-01

Physical activity and exercise interventions are useful in facilitating the functional recovery of those with chronic stroke and, routinely, are gait-specific. While treadmill training has proven useful in gait performance recovery post-stroke, its efficacy on balance dysfunction has not been  systematically reviewed. The purpose of this systematic review was to determine the effect of treadmill training (TT) interventions on balance dysfunction in individuals with chronic stroke. A systematic literature search of PubMed, EMBASE, and CINAHL was performed. Eligible randomized controlled trials were published between 2007 and 2016. Selected trials investigated TT interventions in persons with chronic stroke and implemented at least one objective balance measure. Methodological quality was assessed using PEDro criteria. Eight studies met eligibility criteria and were included in the qualitative analysis. Studies differed in TT implementation and use of adjunctive treatments; however, all trials demonstrated improvements in balance measures that were as effective, if not more so, than conventional physical therapy treatments, including targeted balance training. This review recognized moderate evidence in favor of TT interventions in balance and stroke rehabilitation programs. With TT, intensity may be a more critical factor than specificity and may offer additional carryover to recovery parameters of postural control and balance, beyond gait performance. It is recommended that clinicians utilizing TT incorporate objective measures of balance to assess the potential for skill transference and improvements in balance. Higher quality studies and additional research are needed to denote critical parameters by which improvements in balance may be optimized.

Interventions for heartburn in pregnancy

PubMed Central

Neilson, James P

2014-01-01

Background Heartburn is a common symptom in pregnancy affecting up to 80% of women in the third trimester. The reasons for the increase in symptoms in pregnancy are not well understood, but the effects of pregnancy hormones on the lower oesophageal sphincter and gastric clearance are thought to play a part. A range of interventions have been used to relieve symptoms including advice on diet and lifestyle, antacids, antihistamines, and proton pump inhibitors. The safety and effectiveness of these interventions to relieve heartburn in pregnancy have not been established. Objectives To assess the effect of interventions to relieve heartburn in pregnancy. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (April 2008). We updated this search on 10 November 2012 and added the results to the awaiting classification section of the review. Selection criteria We included randomised controlled trials evaluating interventions to relieve heartburn. Data collection and analysis We assessed eligibility for inclusion and extracted data independently. Main results Three studies were eligible for inclusion, together they included a total of 286 women. All three were placebo controlled trials, each examining a different medication to relieve heartburn (intramuscular prostigmine, an antacid preparation and an antacid plus ranitidine). All three produced positive findings in favour of the intervention groups. It was not possible to pool findings from studies to produce an overall treatment effect. Authors’ conclusions There was little information to draw conclusions on the overall effectiveness of interventions to relieve heartburn in pregnancy. [Note: the two citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.] PMID:18843742

Methods for the design of vasomotor symptom trials: the menopausal strategies: finding lasting answers to symptoms and health network.

PubMed

Newton, Katherine M; Carpenter, Janet S; Guthrie, Katherine A; Anderson, Garnet L; Caan, Bette; Cohen, Lee S; Ensrud, Kristine E; Freeman, Ellen W; Joffe, Hadine; Sternfeld, Barbara; Reed, Susan D; Sherman, Sheryl; Sammel, Mary D; Kroenke, Kurt; Larson, Joseph C; Lacroix, Andrea Z

2014-01-01

This report describes the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network and methodological issues addressed in designing and implementing vasomotor symptom trials. Established in response to a National Institutes of Health request for applications, the network was charged with conducting rapid throughput randomized trials of novel and understudied available interventions postulated to alleviate vasomotor and other menopausal symptoms. Included are descriptions of and rationale for criteria used for interventions and study selection, common eligibility and exclusion criteria, common primary and secondary outcome measures, consideration of placebo response, establishment of a biorepository, trial duration, screening and recruitment, statistical methods, and quality control. All trial designs are presented, including the following: (1) a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the effectiveness of the selective serotonin reuptake inhibitor escitalopram in reducing vasomotor symptom frequency and severity; (2) a two-by-three factorial design trial to test three different interventions (yoga, exercise, and ω-3 supplementation) for the improvement of vasomotor symptom frequency and bother; and (3) a three-arm comparative efficacy trial of the serotonin-norepinephrine reuptake inhibitor venlafaxine and low-dose oral estradiol versus placebo for reducing vasomotor symptom frequency. The network's structure and governance are also discussed. The methods used in and the lessons learned from the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health trials are shared to encourage and support the conduct of similar trials and to encourage collaborations with other researchers.

Target-D: a stratified individually randomized controlled trial of the diamond clinical prediction tool to triage and target treatment for depressive symptoms in general practice: study protocol for a randomized controlled trial.

PubMed

Gunn, Jane; Wachtler, Caroline; Fletcher, Susan; Davidson, Sandra; Mihalopoulos, Cathrine; Palmer, Victoria; Hegarty, Kelsey; Coe, Amy; Murray, Elizabeth; Dowrick, Christopher; Andrews, Gavin; Chondros, Patty

2017-07-20

Depression is a highly prevalent and costly disorder. Effective treatments are available but are not always delivered to the right person at the right time, with both under- and over-treatment a problem. Up to half the patients presenting to general practice report symptoms of depression, but general practitioners have no systematic way of efficiently identifying level of need and allocating treatment accordingly. Therefore, our team developed a new clinical prediction tool (CPT) to assist with this task. The CPT predicts depressive symptom severity in three months' time and based on these scores classifies individuals into three groups (minimal/mild, moderate, severe), then provides a matched treatment recommendation. This study aims to test whether using the CPT reduces depressive symptoms at three months compared with usual care. The Target-D study is an individually randomized controlled trial. Participants will be 1320 general practice patients with depressive symptoms who will be approached in the practice waiting room by a research assistant and invited to complete eligibility screening on an iPad. Eligible patients will provide informed consent and complete the CPT on a purpose-built website. A computer-generated allocation sequence stratified by practice and depressive symptom severity group, will randomly assign participants to intervention (treatment recommendation matched to predicted depressive symptom severity group) or comparison (usual care plus Target-D attention control) arms. Follow-up assessments will be completed online at three and 12 months. The primary outcome is depressive symptom severity at three months. Secondary outcomes include anxiety, mental health self-efficacy, quality of life, and cost-effectiveness. Intention-to-treat analyses will test for differences in outcome means between study arms overall and by depressive symptom severity group. To our knowledge, this is the first depressive symptom stratification tool designed for primary care which takes a prognosis-based approach to provide a tailored treatment recommendation. If shown to be effective, this tool could be used to assist general practitioners to implement stepped mental-healthcare models and contribute to a more efficient and effective mental health system. Australian New Zealand Clinical Trials Registry (ANZCTR 12616000537459 ). Retrospectively registered on 27 April 2016. See Additional file 1 for trial registration data.

Reporting of Telehealth-Delivered Dietary Intervention Trials in Chronic Disease: Systematic Review.

PubMed

Warner, Molly M; Kelly, Jaimon T; Reidlinger, Dianne P; Hoffmann, Tammy C; Campbell, Katrina L

2017-12-11

Telehealth-delivered dietary interventions are effective for chronic disease management and are an emerging area of clinical practice. However, to apply interventions from the research setting in clinical practice, health professionals need details of each intervention component. The aim of this study was to evaluate the completeness of intervention reporting in published dietary chronic disease management trials that used telehealth delivery methods. Eligible randomized controlled trial publications were identified through a systematic review. The completeness of reporting of experimental and comparison interventions was assessed by two independent assessors using the Template for Intervention Description and Replication (TIDieR) checklist that consists of 12 items including intervention rationale, materials used, procedures, providers, delivery mode, location, when and how much intervention delivered, intervention tailoring, intervention modifications, and fidelity. Where reporting was incomplete, further information was sought from additional published material and through email correspondence with trial authors. Within the 37 eligible trials, there were 49 experimental interventions and 37 comparison interventions. One trial reported every TIDieR item for their experimental intervention. No publications reported every item for the comparison intervention. For the experimental interventions, the most commonly reported items were location (96%), mode of delivery (98%), and rationale for the essential intervention elements (96%). Least reported items for experimental interventions were modifications (2%) and intervention material descriptions (39%) and where to access them (20%). Of the 37 authors, 14 responded with further information, and 8 could not be contacted. Many details of the experimental and comparison interventions in telehealth-delivered dietary chronic disease management trials are incompletely reported. This prevents accurate interpretation of trial results and implementation of effective interventions in clinical practice. ©Molly M Warner, Jaimon T Kelly, Dianne P Reidlinger, Tammy C Hoffmann, Katrina L Campbell. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 11.12.2017.

Interventions to modify sexual risk behaviours for preventing HIV in homeless youth

PubMed Central

Naranbhai, Vivek; Karim, Quarraisha Abdool; Meyer-Weitz, Anna

2013-01-01

Background Homeless youth are at high risk for HIV infection as a consequence of risky sexual behavior. Interventions in homeless youth are challenging. Assessment of the effectiveness of interventions to modify sexual risk behaviours for preventing HIV in homeless youth is needed. Objectives To evaluate and summarize the effectiveness of interventions for modifying sexual risk behaviours and preventing transmission of HIV among homeless youth. Search methods We searched electronic databases (CENTRAL, Medline, EMBASE, AIDSearch, Gateway, PsycInfo, LILACS), reference lists of eligible articles, international health agency publication lists, and clinical trial registries. The search was updated January 2010. We contacted authors of published reports and other key role players. Selection criteria Randomized studies of interventions to modify sexual risk behavior (biological, self-report sexual-risk behavior or health seeking behavior) in homeless youth (12–24 years). Data collection and analysis Data from eligible studies were extracted by two reviewers. We assessed risk of bias per the Cochrane Collaborations tool. None of the eligible studies reported any primary biological outcomes for this review and the reporting of self-report sexual risk behavior outcomes was highly variable across studies precluding calculation of summary measures of effect; we present the outcomes descriptively for each study. We contacted authors for missing or ambiguous data. Results We identified three eligible studies after screening a total of 255 unique records. All three were performed in the United States of America and recruited substance-abusing male and female adolescents (total N=615) through homeless shelters into randomised controlled trials of independent and non-overlapping behavioural interventions. The three trials differed in theoretical background, delivery method, dosage (number of sessions,) content and outcome assessments. Overall, the variability in delivery and outcomes precluded estimation of summary of effect measures. We assessed the risk of bias to be high for each of the studies. Whilst some effect of the interventions on outcome measures were reported, heterogeneity and lack of robustness in these studies necessitate caution in interpreting the effectiveness of these interventions. Authors’ conclusions The body of evidence does not permit conclusions on the impact of interventions to modify sexual risk behaviour in homeless youth. More research is required. While the psychosocial and contextual factors that fuel sexual risk behaviours among homeless youth challenge stringent methodologies of RCT’s, novel ways for program delivery and trial retention are in need of development. Future trials should endeavour to comply with rigorous methodology in design, delivery, outcome measurement and reporting. PMID:21249691

Blastocyst culture using single versus sequential media in clinical IVF: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Sfontouris, Ioannis A; Martins, Wellington P; Nastri, Carolina O; Viana, Iara G R; Navarro, Paula A; Raine-Fenning, Nick; van der Poel, Sheryl; Rienzi, Laura; Racowsky, Catherine

2016-10-01

The purpose of this study was to undertake a review of the available evidence comparing the use of a single medium versus sequential media for embryo culture to the blastocyst stage in clinical IVF. We searched the Cochrane Central, PubMed, Scopus, ClinicalTrials.gov, Current Controlled Trials and WHO International Clinical Trials Registry Platform to identify randomized controlled trials comparing single versus sequential media for blastocyst culture and ongoing pregnancy rate. Included studies randomized either oocytes/zygotes or women. Eligible oocyte/zygote studies were analyzed to assess the risk difference (RD) and 95 % confidence intervals (CI) between the two media systems; eligible woman-based studies were analyzed to assess the risk ratio (RR) and 95 % CI for clinical pregnancy rate. No differences were observed between single and sequential media for either ongoing pregnancy per randomized woman (relative risk (RR) = 0.9, 95 % CI = 0.7 to 1.3, two studies including 246 women, I 2  = 0 %) or clinical pregnancy per randomized woman (RR = 1.0, 95 % CI = 0.7 to 1.4, one study including 100 women); or miscarriage per clinical pregnancy: RR = 1.3, 95 % CI = 0.4 to 4.3, two studies including 246 participants, I 2  = 0 %). Single media use was associated with an increase blastocyst formation per randomized oocyte/zygote (relative distribution (RD) = +0.06, 95 % CI = +0.01 to +0.12, ten studies including 7455 oocytes/zygotes, I 2  = 83 %) but not top/high blastocyst formation (RD = +0.05, 95 % CI = -0.01 to +0.11, five studies including 3879 oocytes/zygotes, I 2  = 93 %). The overall quality of the evidence was very low for all these four outcomes. Although using a single medium for extended culture has some practical advantages and blastocyst formation rates appear to be higher, there is insufficient evidence to recommend either sequential or single-step media as being superior for the culture of embryos to days 5/6. Future studies comparing these two media systems in well-designed trials should be performed.

Maintained physical activity and physiotherapy in the management of distal upper limb pain – a protocol for a randomised controlled trial (the arm pain trial)

PubMed Central

2014-01-01

Background Distal upper limb pain (pain affecting the elbow, forearm, wrist, or hand) can be non-specific, or can arise from specific musculoskeletal disorders. It is clinically important and costly, the best approach to clinical management is unclear. Physiotherapy is the standard treatment and, while awaiting treatment, advice is often given to rest and avoid strenuous activities, but there is no evidence base to support these strategies. This paper describes the protocol of a randomised controlled trial to determine, among patients awaiting physiotherapy for distal arm pain, (a) whether advice to remain active and maintain usual activities results in a long-term reduction in arm pain and disability, compared with advice to rest; and (b) whether immediate physiotherapy results in a long-term reduction in arm pain and disability, compared with physiotherapy delivered after a seven week waiting list period. Methods/Design Between January 2012 and January 2014, new referrals to 14 out-patient physiotherapy departments were screened for potential eligibility. Eligible and consenting patients were randomly allocated to one of the following three groups in equal numbers: 1) advice to remain active, 2) advice to rest, 3) immediate physiotherapy. Patients were and followed up at 6, 13, and 26 weeks post-randomisation by self-complete postal questionnaire and, at six weeks, patients who had not received physiotherapy were offered it at this time. The primary outcome is the proportion of patients free of disability at 26 weeks, as determined by the modified DASH (Disabilities of the Arm, Shoulder and Hand) questionnaire. We hypothesise (a) that advice to maintain usual activities while awaiting physiotherapy will be superior than advice to rest the arm; and (b) that fast-track physiotherapy will be superior to normal (waiting list) physiotherapy. These hypotheses will be examined using an intention-to-treat analysis. Discussion Results from this trial will contribute to the evidence base underpinning the clinical management of patients with distal upper limb pain, and in particular, will provide guidance on whether they should be advised to rest the arm or remain active within the limits imposed by their symptoms. Trial registration Registered on http://www.controlled-trials.com (reference number: ISRCTN79085082). PMID:24612447

Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies.

PubMed

Te Morenga, Lisa; Mallard, Simonette; Mann, Jim

2012-01-15

To summarise evidence on the association between intake of dietary sugars and body weight in adults and children. Systematic review and meta-analysis of randomised controlled trials and prospective cohort studies. OVID Medline, Embase, PubMed, Cumulative Index to Nursing and Allied Health Literature, Scopus, and Web of Science (up to December 2011). Eligible studies reported the intake of total sugars, intake of a component of total sugars, or intake of sugar containing foods or beverages; and at least one measure of body fatness. Minimum duration was two weeks for trials and one year for cohort studies. Trials of weight loss or confounded by additional medical or lifestyle interventions were excluded. Study selection, assessment, validity, data extraction, and analysis were undertaken as specified by the Cochrane Collaboration and the GRADE working group. For trials, we pooled data for weight change using inverse variance models with random effects. We pooled cohort study data where possible to estimate effect sizes, expressed as odds ratios for risk of obesity or β coefficients for change in adiposity per unit of intake. 30 of 7895 trials and 38 of 9445 cohort studies were eligible. In trials of adults with ad libitum diets (that is, with no strict control of food intake), reduced intake of dietary sugars was associated with a decrease in body weight (0.80 kg, 95% confidence interval 0.39 to 1.21; P<0.001); increased sugars intake was associated with a comparable weight increase (0.75 kg, 0.30 to 1.19; P=0.001). Isoenergetic exchange of dietary sugars with other carbohydrates showed no change in body weight (0.04 kg, -0.04 to 0.13). Trials in children, which involved recommendations to reduce intake of sugar sweetened foods and beverages, had low participant compliance to dietary advice; these trials showed no overall change in body weight. However, in relation to intakes of sugar sweetened beverages after one year follow-up in prospective studies, the odds ratio for being overweight or obese increased was 1.55 (1.32 to 1.82) among groups with the highest intake compared with those with the lowest intake. Despite significant heterogeneity in one meta-analysis and potential bias in some trials, sensitivity analyses showed that the trends were consistent and associations remained after these studies were excluded. Among free living people involving ad libitum diets, intake of free sugars or sugar sweetened beverages is a determinant of body weight. The change in body fatness that occurs with modifying intakes seems to be mediated via changes in energy intakes, since isoenergetic exchange of sugars with other carbohydrates was not associated with weight change.

Improved quality monitoring of multi-center acupuncture clinical trials in China

PubMed Central

2009-01-01

Background In 2007, the Chinese Science Division of the State Administration of Traditional Chinese Medicine(TCM) convened a special conference to discuss quality control for TCM clinical research. Control and assurance standards were established to guarantee the quality of clinical research. This paper provides practical guidelines for implementing strict and reproducible quality control for acupuncture randomized controlled trials (RCTs). Methods A standard quality control program (QCP) was established to monitor the quality of acupuncture trials. Case report forms were designed; qualified investigators, study personnel and data management personnel were trained. Monitors, who were directly appointed by the project leader, completed the quality control programs. They guaranteed data accuracy and prevented or detected protocol violations. Clinical centers and clinicians were audited, the randomization system of the centers was inspected, and the treatment processes were audited as well. In addition, the case report forms were reviewed for completeness and internal consistency, the eligibility and validity of the patients in the study was verified, and data was monitored for compliance and accuracy. Results and discussion The monitors complete their reports and submit it to quality assurance and the sponsors. Recommendations and suggestions are made for improving performance. By holding regular meetings to discuss improvements in monitoring standards, the monitors can improve quality and efficiency. Conclusions Supplementing and improving the existed guidelines for quality monitoring will ensure that large multi-centre acupuncture clinical trials will be considered as valid and scientifically stringent as pharmaceutical clinical trials. It will also develop academic excellence and further promote the international recognition of acupuncture. PMID:20035630

Meditation for adults with haematological malignancies.

PubMed

Salhofer, Ines; Will, Andrea; Monsef, Ina; Skoetz, Nicole

2016-02-03

Malignant neoplasms of the lymphoid or myeloid cell lines including lymphoma, leukaemia and myeloma are referred to as haematological malignancies. Complementary and alternative treatment options such as meditation practice or yoga are becoming popular by treating all aspects of the disease including physical and psychological symptoms. However, there is still unclear evidence about meditation's effectiveness, and how its practice affects the lives of haematologically-diseased patients. This review aims to assess the benefits and harms of meditation practice as an additional treatment to standard care for adults with haematological malignancies. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 8, 2015), MEDLINE (1950 to August 2015), databases of ongoing trials, the metaRegister of Controlled Trials (mRCT) (http://www.controlled-trials.com/mrct/), conference proceedings of annual meetings of: the American Society of Hematology; American Society of Clinical Oncology; European Hematology Association; European Congress for Integrative Medicine; and Global Advances in Health and Medicine (2010 to 2015). We included randomised controlled trials (RCTs) using meditation practice for adult patients with haematological malignancies. Two review authors independently extracted data from eligible studies and assessed the risk of bias according to predefined criteria. We evaluated quality of life and depression. The other outcomes of overall survival, anxiety, fatigue, quality of sleep and adverse events could not be evaluated, because they were not assessed in the included trial. We included only one small trial published as an abstract article. The included study investigated the effects of meditation practice on patients newly hospitalised with acute leukaemia. Ninety-one participants enrolled in the study, but only 42 participants remained in the trial throughout the six-month follow-up period and were eligible for analysis. There was no information provided about the average age and sex of the study population. We found a high risk for attrition bias and unclear risk for reporting bias, performance and detection bias because of missing data due to abstract publication only, thus we judged the overall risk of bias as high. According to the GRADE criteria, we judged the overall quality of the body of evidence for all predefined outcomes as 'very low', due to the extent of missing data on the study population, and the small sample size.As the abstract publication did not provide numbers and results except P values, we are not able to give more details.Meditation practice might be beneficial for the quality of life of haematologically-diseased patients, with higher scores for participants in the mediation arms compared to the participants in the usual care control group (low quality of evidence). Levels of depression decreased for those practising meditation in both the spiritually-framed meditation group and the secularly-focused meditation group in comparison to the usual care control group, whose levels of depression remained constant (low quality of evidence). The influence of meditation practice on overall survival, fatigue, anxiety, quality of sleep and adverse events remained unclear, as these outcomes were not evaluated in the included trial. To estimate the effects of meditation practice for patients suffering from haematological malignancies, more high quality randomised controlled trials are needed. At present there is not enough information available on the effects of meditation in haematologically-diseased patients to draw any conclusion.

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.

PedVacc 002: a phase I/II randomized clinical trial of MVA.HIVA vaccine administered to infants born to human immunodeficiency virus type 1-positive mothers in Nairobi.

PubMed

Njuguna, Irene N; Ambler, Gwen; Reilly, Marie; Ondondo, Beatrice; Kanyugo, Mercy; Lohman-Payne, Barbara; Gichuhi, Christine; Borthwick, Nicola; Black, Antony; Mehedi, Shams-Rony; Sun, Jiyu; Maleche-Obimbo, Elizabeth; Chohan, Bhavna; John-Stewart, Grace C; Jaoko, Walter; Hanke, Tomáš

2014-10-07

A safe, effective vaccine for breastfeeding infants born to HIV-1-positive mothers could complement antiretroviral therapy (ART) for prevention of mother-to-child transmission of HIV-1. To date, only a few HIV-1 vaccine candidates have been tested in infants. A phase I/II randomized controlled trial PedVacc 002 was conducted to determine the safety and immunogenicity of a single, low dose of MVA.HIVA vaccine delivered intramuscularly to healthy 20-week-old infants born to HIV-1-positive mothers in Nairobi, Kenya. Pregnant HIV-1-positive women in the 2nd/3rd trimester of gestation were enrolled, provided with ART and self-selected their infant-feeding modality. Infants received nevirapine and cotrimoxazole prophylaxis. At 20 weeks of age, eligible HIV-1-negative infants were randomized to vaccine versus no-treatment arms and followed to 48 weeks of age for assessments of vaccine safety, HIV-1-specific T-cell responses and antibodies to routine childhood vaccines. Between February and November 2010, 182 mothers were screened, 104 were eligible and followed on ART during pregnancy/postpartum, of whom 73 had eligible infants at 20 weeks postpartum. Thirty-six infants were randomized to vaccine and 37 to no treatment. Eighty-four percent of infants breastfed, and retention at 48 weeks was 99%. Adverse events were rare and similar between the two arms. HIV-1-specific T-cell frequencies in interferon-γ ELISPOT assay were transiently higher in the MVA.HIVA arm (p=0.002), but not above the threshold for a positive assay. Protective antibody levels were adequate and similar between arms for all routine childhood vaccines except HBV, where 71% of MVA.HIVA subjects compared to 92% of control subjects were protected (p=0.05). This trial tested for the first time an MVA-vectored candidate HIV-1 vaccine in HIV-1-exposed infants in Africa, demonstrating trial feasibility and vaccine safety, low immunogenicity, and compatibility with routine childhood vaccinations. These results are reassuring for use of the MVA vector in more potent prime-boost regimens. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

A clinical carepath for obese pregnant women: A pragmatic pilot cluster randomized controlled trial.

PubMed

McDonald, Sarah D; Viaje, Kristen A; Rooney, Rebecca A; Jarde, Alexander; Giglia, Lucia; Maxwell, Cynthia V; Small, David; Kelly, Tracy Pearce; Midwifery, B H Sc; Sabatino, Lisa; Thabane, Lehana

2018-05-17

Obese women are at increased risks for complications during pregnancy, birth and in their infants. Although guidelines have been established for the clinical care of obese pregnant women, management is sometimes suboptimal. Our goal was to determine the feasibility of implementing and testing a clinical carepath for obese pregnant women compared to standard care, in a pilot cluster randomized controlled trial (RCT). A pragmatic pilot cluster RCT was conducted, randomly allocating eight clinics to the carepath or standard care for obese pregnant women. Women were eligible if they had a prepregnancy body mass index of ≥ 30 kg/m 2 and a viable singleton < 21 weeks. The primary outcomes were the feasibility of conducting a full-scale cluster RCT (defined as > 80%: randomization of clinics, use in eligible women, and completeness of follow-up) and of the intervention (defined as > 80%: compliance with each step in the carepath, and recommendation of the carepath by clinicians to a colleague). All eight approached clinics agreed to participate and were randomized. Half of the intervention clinics used the carepath, resulting in < 80% uptake of eligible women. High follow-up (99.5%) was achieved, in 188 of 189 women. The carepath was feasible for numerous guideline-directed recommendations for screening, but less so for counselling topics. When the carepath was used in the majority of women, all clinicians, most of whom were midwives, reported they would recommend it to a colleague. The intervention group had significantly higher overall adherence to the guideline recommendations compared to control (relative risk 1.71, 95% confidence interval 1.57-1.87). In this pragmatic pilot cluster RCT, a guideline-directed clinical carepath improved some aspects of care of obese pregnant women and was recommended by clinicians, particularly midwives. A cluster RCT may not be feasible in a mix of obstetric and midwifery clinics, but may be feasible in midwifery clinics. This pragmatic pilot cluster RCT was registered on clinicaltrials.gov (identifier: NCT02534051 ).

Effect of a Behavioral Self-Regulation Intervention on Patient Adherence to Fluid-Intake Restrictions in Hemodialysis: a Randomized Controlled Trial.

PubMed

Howren, M Bryant; Kellerman, Quinn D; Hillis, Stephen L; Cvengros, Jamie; Lawton, William; Christensen, Alan J

2016-04-01

The purpose of this study is to evaluate the efficacy of a behavioral self-regulation intervention vs. active control condition using a parallel-group randomized clinical trial with a sample of center hemodialysis patients with chronic kidney disease. Participants were recruited from 8 hemodialysis treatment centers in the Midwest. Eligible patients were (a) fluid nonadherent as defined by an interdialytic weight gain >2.5 kg over a 4-week period, (b) >18 years of age, (c) English-speaking without severe cognitive impairment, (d) treated with center-based hemodialysis for >3 months, and (e) not living in a care facility in which meals were managed. Medical records were used to identify eligible patients. Patients were randomly assigned to either a behavioral self-regulation intervention or active control condition in which groups of 3-8 patients met for hour-long, weekly sessions for 7 weeks at their usual hemodialysis clinic. Primary analyses were intention-to-treat. Sixty-one patients were randomized to the intervention while 58 were assigned to the attention-placebo support and discussion control. Covariate-adjusted between-subjects analyses demonstrated no unique intervention effect for the primary outcome, interdialytic weight gain (β = 0.13, p = 0.48). Significant within-subjects improvement over time was observed for the intervention group (β = -0.32, p = 0.014). The present study found that participation in a behavioral self-regulation intervention resulted in no unique intervention effect on a key indicator of adherence for those with severe chronic kidney disease. There was, however, modest within-subjects improvement in interdialytic weight gain for the intervention group which meshes with other evidence showing the utility of behavioral interventions in this patient population. ClinicalTrials.gov Identifier: NCT01066949.

Effectiveness of Workplace Weight Management Interventions: a Systematic Review.

PubMed

Weerasekara, Yasoma Kumari; Roberts, Susan B; Kahn, Mira A; LaVertu, Amy E; Hoffman, Ben; Das, Sai Krupa

2016-06-01

A systematic review was conducted of randomized trials of workplace weight management interventions, including trials with dietary, physical activity, environmental, behavioral, and incentive-based components. Main outcomes were defined as change in weight-related measures. Keywords related to weight management and workplace interventions were used to search relevant databases, and 23 eligible studies were reviewed in detail using a data extraction form and quality assessment checklist. The trials were conducted mainly in the USA and Europe, with four additional countries represented. Interventions were mostly multicomponent and were implemented in both sexes and in a range of employment categories. Intervention effectiveness appeared unrelated to region of the world and was highest in 6-12-month trials. The results ranged widely from clinically significant 8.8-kg weight loss in one trial to less effective than the control treatment in others. Some workplace interventions achieve clinically significant benefits, and further studies are needed to replicate those results in wider sociocultural and geographical contexts.

Implementing the PAIN RelieveIt Randomized Controlled Trial in Hospice Care: Mechanisms for Success and Meeting PCORI Methodology Standards.

PubMed

Ezenwa, Miriam O; Suarez, Marie L; Carrasco, Jesus D; Hipp, Theresa; Gill, Anayza; Miller, Jacob; Shea, Robert; Shuey, David; Zhao, Zhongsheng; Angulo, Veronica; McCurry, Timothy; Martin, Joanna; Yao, Yingwei; Molokie, Robert E; Wang, Zaijie Jim; Wilkie, Diana J

2017-07-01

This purpose of this article is to describe how we adhere to the Patient-Centered Outcomes Research Institute's (PCORI) methodology standards relevant to the design and implementation of our PCORI-funded study, the PAIN RelieveIt Trial. We present details of the PAIN RelieveIt Trial organized by the PCORI methodology standards and components that are relevant to our study. The PAIN RelieveIt Trial adheres to four PCORI standards and 21 subsumed components. The four standards include standards for formulating research questions, standards associated with patient centeredness, standards for data integrity and rigorous analyses, and standards for preventing and handling missing data. In the past 24 months, we screened 2,837 cancer patients and their caregivers; 874 dyads were eligible; 223.5 dyads consented and provided baseline data. Only 55 patients were lost to follow-up-a 25% attrition rate. The design and implementation of the PAIN RelieveIt Trial adhered to PCORI's methodology standards for research rigor.

Support and Assessment for Fall Emergency Referrals (SAFER) 2: a cluster randomised trial and systematic review of clinical effectiveness and cost-effectiveness of new protocols for emergency ambulance paramedics to assess older people following a fall with referral to community-based care when appropriate.

PubMed

Snooks, Helen A; Anthony, Rebecca; Chatters, Robin; Dale, Jeremy; Fothergill, Rachael; Gaze, Sarah; Halter, Mary; Humphreys, Ioan; Koniotou, Marina; Logan, Phillipa; Lyons, Ronan; Mason, Suzanne; Nicholl, Jon; Peconi, Julie; Phillips, Ceri; Phillips, Judith; Porter, Alison; Siriwardena, A Niroshan; Smith, Graham; Toghill, Alun; Wani, Mushtaq; Watkins, Alan; Whitfield, Richard; Wilson, Lynsey; Russell, Ian T

2017-03-01

Emergency calls are frequently made to ambulance services for older people who have fallen, but ambulance crews often leave patients at the scene without any ongoing care. We evaluated a new clinical protocol which allowed paramedics to assess older people who had fallen and, if appropriate, refer them to community-based falls services. To compare outcomes, processes and costs of care between intervention and control groups; and to understand factors which facilitate or hinder use. Cluster randomised controlled trial. Participating paramedics at three ambulance services in England and Wales were based at stations randomised to intervention or control arms. Participants were aged 65 years and over, attended by a study paramedic for a fall-related emergency service call, and resident in the trial catchment areas. Intervention paramedics received a clinical protocol with referral pathway, training and support to change practice. Control paramedics continued practice as normal. The primary outcome comprised subsequent emergency health-care contacts (emergency admissions, emergency department attendances, emergency service calls) or death at 1 month and 6 months. Secondary outcomes included pathway of care, ambulance service operational indicators, self-reported outcomes and costs of care. Those assessing outcomes remained blinded to group allocation. Across sites, 3073 eligible patients attended by 105 paramedics from 14 ambulance stations were randomly allocated to the intervention group, and 2841 eligible patients attended by 110 paramedics from 11 stations were randomly allocated to the control group. After excluding dissenting and unmatched patients, 2391 intervention group patients and 2264 control group patients were included in primary outcome analyses. We did not find an effect on our overall primary outcome at 1 month or 6 months. However, further emergency service calls were reduced at both 1 month and 6 months; a smaller proportion of patients had made further emergency service calls at 1 month (18.5% vs. 21.8%) and the rate per patient-day at risk at 6 months was lower in the intervention group (0.013 vs. 0.017). Rate of conveyance to emergency department at index incident was similar between groups. Eight per cent of trial eligible patients in the intervention arm were referred to falls services by attending paramedics, compared with 1% in the control arm. The proportion of patients left at scene without further care was lower in the intervention group than in the control group (22.6% vs. 30.3%). We found no differences in duration of episode of care or job cycle. No adverse events were reported. Mean cost of the intervention was £17.30 per patient. There were no significant differences in mean resource utilisation, utilities at 1 month or 6 months or quality-adjusted life-years. In total, 58 patients, 25 paramedics and 31 stakeholders participated in focus groups or interviews. Patients were very satisfied with assessments carried out by paramedics. Paramedics reported that the intervention had increased their confidence to leave patients at home, but barriers to referral included patients' social situations and autonomy. Findings indicate that this new pathway may be introduced by ambulance services at modest cost, without risk of harm and with some reductions in further emergency calls. However, we did not find evidence of improved health outcomes or reductions in overall NHS emergency workload. Further research is necessary to understand issues in implementation, the costs and benefits of e-trials and the performance of the modified Falls Efficacy Scale. Current Controlled Trials ISRCTN60481756 and PROSPERO CRD42013006418. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 13. See the NIHR Journals Library website for further project information.

[Hyaluronate sodium treatment for internal derangement of temporomandibular joint: a systematic review based on randomized controlled trials].

PubMed

Li, Chunjie; Zhang, Yifan; Jia, Yuanyuan; Lü, Jun; Li, Longjiang; Shi, Zong-Dao

2011-10-01

To assess the efficacy and safety of hyaluronate sodium (HS) for internal derangement of temporomandibular joint by means of systematic review on relevant randomized controlled trials. After identifing the study question of the efficacy and safety of HS for internal derangement of temporomandibular joint, Medline, Cochrane Controlled Trials Register, EMBASE, OPEN SIGLE and CBM were searched electronically till October 3rd 2010. Hand-searching covering 19 dental journals in Chinese were also performed. Risk of bias assessment, with Cochrane Collaboration's tool, and data extraction of included studies were conducted by two reviewers in duplicate. Meta analysis was done with Revman 5.0.23 and the quality of evidence was evaluated by GRADE. 10 randomized controlled trials met the eligibility criteria and were included. All these studies had unclear risk of bias. When compared with negative control, HS showed a significant advantage on maximal mouth opening in short and long-term (P < 0.05), and clinical overall assessment in short-term (P < 0.05), but its effect on pain control and long-term effect on clinical overall assessment had no extra benefit (P > 0.05). Additionally, when compared with glucocorticoids, the participants who received HS injection would get a better clinical overall assessment in short-term and less adverse drug reactions (P < 0.05), but presented a similar temporomandibular joint pain relief and maximal mouth opening (P > 0.05). To a certain extent, HS had good efficacy and better safety than controls when treating internal derangement of temporomandibular joint. However, as the quality of some included studies were limited, more randomized controlled trials are needed to reinforce the conclusion.

Antibiotic prophylaxis for operative vaginal delivery.

PubMed

Liabsuetrakul, T; Choobun, T; Peeyananjarassri, K; Islam, M

2004-01-01

Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics are prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum and/or forceps deliveries. We searched the Cochrane Pregnancy and Childbirth Group trials register (November 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003) and MEDLINE (1966 to November 2003). All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Four reviewers assessed trial eligibility and methodological quality. Two reviewers extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all reviewers. We assessed methodological quality of the included trial using the standard Cochrane criteria and the CONSORT statement of randomised controlled trials. We calculated the relative risks using a fixed effect model and all the reviewers interpreted and discussed the results. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. This trial identified only two out of the nine outcomes specified in this review. It reported seven women with endomyometritis in the group given no antibiotic and none in prophylactic antibiotic group. This difference did not reach statistical significance, but the relative risk reduction was 93% (relative risks 0.07; 95% confidence interval (CI) 0.00 to 1.21). There was no difference in the length of hospital stay between the two groups (weighted mean difference 0.09 days; 95% CI -0.23 to 0.41). The data were too few and of insufficient quality to make any recommendations for practice. Future research on antibiotic prophylaxis for operative vaginal delivery is needed to conclude whether it is useful for reducing postpartum morbidity.

Reasons for Ineligibility in Phase 1 and 2A HIV Vaccine Clinical Trials at Kenya Aids Vaccine Initiative (KAVI), Kenya

PubMed Central

Omosa-Manyonyi, Gloria S.; Jaoko, Walter; Anzala, Omu; Ogutu, Hilda; Wakasiaka, Sabina; Malogo, Roselyn; Nyange, Jacqueline; Njuguna, Pamela; Ndinya-Achola, Jeckoniah; Bhatt, Kirana; Farah, Bashir; Oyaro, Micah; Schmidt, Claudia; Priddy, Frances; Fast, Patricia

2011-01-01

Background With the persistent challenges towards controlling the HIV epidemic, there is an ongoing need for research into HIV vaccines and drugs. Sub-Saharan African countries - worst affected by the HIV pandemic - have participated in the conduct of clinical trials for HIV vaccines. In Kenya, the Kenya AIDS Vaccine Initiative (KAVI) at the University of Nairobi has conducted HIV vaccine clinical trials since 2001. Methodology Participants were recruited after an extensive informed consent process followed by screening to determine eligibility. Screening included an assessment of risk behavior, medical history and physical examination, and if clinically healthy, laboratory testing. In the absence of locally derived laboratory reference ranges, the ranges used in these trials were derived from populations in the West. Principal findings Two hundred eighty-one participants were screened between 2003 and 2006 for two clinical trials. Of these, 167 (59.4%) met the inclusion/exclusion criteria. Overall, laboratory abnormalities based on the non-indigenous laboratory references used were the most frequent reasons (61.4%) for ineligibility. Medical abnormalities contributed 30.7% of the total reasons for ineligibility. Based on the laboratory reference intervals now developed from East and Southern Africa, those ineligible due to laboratory abnormalities would have been 46.3%. Of the eligible participants, 18.6% declined enrolment. Conclusions Participant recruitment for HIV vaccine clinical trials is a rigorous and time-consuming exercise. Over 61% of the screening exclusions in clinically healthy people were due to laboratory abnormalities. It is essential that laboratory reference ranges generated from local populations for laboratory values be used in the conduct of clinical trials to avoid unnecessary exclusion of willing participants and to avoid over-reporting of adverse events for enrolled participants. Trial registration Protocol IAVI VRC V001 [1]. ClinicalTrials.gov NCT00124007 Protocol IAVI 010 [2] (registration with ClincalTrials.gov is in progress) Protocols IAVI 002 and IAVI 004 are Phase 1 trials only mentioned in introductory paragraphs; details will not be reported. Registration was not required when they were conducted. PMID:21283743

Exercise for patients with major depression: a systematic review with meta-analysis and trial sequential analysis

PubMed Central

Speyer, Helene; Gluud, Christian; Nordentoft, Merete

2017-01-01

Objectives To assess the benefits and harms of exercise in patients with depression. Design Systematic review Data sources Bibliographical databases were searched until 20 June 2017. Eligibility criteria and outcomes Eligible trials were randomised clinical trials assessing the effect of exercise in participants diagnosed with depression. Primary outcomes were depression severity, lack of remission and serious adverse events (eg, suicide) assessed at the end of the intervention. Secondary outcomes were quality of life and adverse events such as injuries, as well as assessment of depression severity and lack of remission during follow-up after the intervention. Results Thirty-five trials enrolling 2498 participants were included. The effect of exercise versus control on depression severity was −0.66 standardised mean difference (SMD) (95% CI −0.86 to −0.46; p<0.001; grading of recommendations assessment, development and evaluation (GRADE): very low quality). Restricting this analysis to the four trials that seemed less affected of bias, the effect vanished into −0.11 SMD (−0.41 to 0.18; p=0.45; GRADE: low quality). Exercise decreased the relative risk of no remission to 0.78 (0.68 to 0.90; p<0.001; GRADE: very low quality). Restricting this analysis to the two trials that seemed less affected of bias, the effect vanished into 0.95 (0.74 to 1.23; p=0.78). Trial sequential analysis excluded random error when all trials were analysed, but not if focusing on trials less affected of bias. Subgroup analyses found that trial size and intervention duration were inversely associated with effect size for both depression severity and lack of remission. There was no significant effect of exercise on secondary outcomes. Conclusions Trials with less risk of bias suggested no antidepressant effects of exercise and there were no significant effects of exercise on quality of life, depression severity or lack of remission during follow-up. Data for serious adverse events and adverse events were scarce not allowing conclusions for these outcomes. Systematic review registration The protocol was published in the journal Systematic Reviews: 2015; 4:40. PMID:28928174

Efficacy and Safety of Zoledronic Acid for Treatment of Postmenopausal Osteoporosis: A Meta-Analysis of Randomized Controlled Trials.

PubMed

Wang, Chao

We conducted a meta-analysis based on eligible studies to assess the efficacy and safety of zoledronic acid treatment for postmenopausal women with osteoporosis. PubMed, Web of Science, and Embase were searched for eligible studies that assessed the efficacy of zoledronic acid in the prevention of fractures among postmenopausal women with osteoporosis. The primary outcomes were new vertebral fracture, nonvertebral fracture, and hip fracture. Secondary outcomes were bone mineral density (BMD) and safety outcomes. A fixed-effect or random-effect model was used to pool the estimates according to the heterogeneity among the included studies. Eight randomized controlled trials, involving 13,335 patients, were included in this meta-analysis. Pooled results showed that treatment with zoledronic acid significantly reduced the incidences of nonvertebral fractures, vertebral fractures, and hip fractures, as compared with placebo. Zoledronic acid was also associated with significant improvement in BMD at lumbar spine, total hip, femoral neck, and trochanter. However, the incidence of any adverse events was higher in the zoledronic acid group than that in the control group, and serious adverse events were comparable between the 2 groups. This meta-analysis indicated that zoledronic acid could significantly reduce the fracture risk and increase BMD in postmenopausal women with osteoporosis. Furthermore, it would not result in serious adverse events. Zoledronic acid could be used as an effective and well-tolerated treatment for postmenopausal women with osteoporosis.

Mobile health as a viable strategy to enhance stroke risk factor control: A systematic review and meta-analysis.

PubMed

Liu, Shimeng; Feng, Wuwei; Chhatbar, Pratik Y; Liu, Yumei; Ji, Xunming; Ovbiagele, Bruce

2017-07-15

With the rapid growth worldwide in cell-phone use, Internet connectivity, and digital health technology, mobile health (mHealth) technology may offer a promising approach to bridge evidence-treatment gaps in stroke prevention. We aimed to evaluate the effectiveness of mHealth for stroke risk factor control through a systematic review and meta-analysis. We searched PubMed from January 1, 2000 to May 17, 2016 using the following keywords: mobile health, mHealth, short message, cellular phone, mobile phone, stroke prevention and control, diabetes mellitus, hypertension, hyperlipidemia and smoking cessation. We performed a meta-analysis of all eligible randomized control clinical trials that assessed a sustained (at least 6months) effect of mHealth. Of 78 articles identified, 13 met eligibility criteria (6 for glycemic control and 7 for smoking cessation) and were included for the final meta-analysis. There were no eligible studies for dyslipidemia or hypertension. mHealth resulted in greater Hemoglobin A1c reduction at 6months (6 studies; 663 subjects; SMD: -0.44; 95% CI: [-0.82, -0.06], P=0.02; Mean difference of decrease in HbA1c: -0.39%; 95% CI: [-0.74, -0.04], P=0.03). mHealth also lead to relatively higher smoking abstinence rates at 6months (7 studies; 9514 subjects; OR: 1.54; 95% CI: [1.24, 1.90], P<0.0001). Our meta-analysis supports that use of mHealth improves glycemic control and smoking abstinence rates. Copyright © 2017 Elsevier B.V. All rights reserved.

Applicability of randomized trials in radiation oncology to standard clinical practice.

PubMed

Apisarnthanarax, Smith; Swisher-McClure, Samuel; Chiu, Wing K; Kimple, Randall J; Harris, Stephen L; Morris, David E; Tepper, Joel E

2013-08-15

Randomized controlled trials (RCTs) are commonly used to inform clinical practice; however, it is unclear how generalizable RCT data are to patients in routine clinical practice. The authors of this report assessed the availability and applicability of randomized evidence guiding medical decisions in a cohort of patients who were evaluated for consideration of definitive management in a radiation oncology clinic. The medical records of consecutive, new patient consultations between January and March 2007 were reviewed. Patient medical decisions were classified as those with (Group 1) or without (Group 2) available, relevant level I evidence (phase 3 RCT) supporting recommended treatments. Group 1 medical decisions were further divided into 3 groups based on the extent of fulfilling eligibility criteria for each RCT: Group 1A included decisions that fulfilled all eligibility criteria; Group 1B, decisions that did not fulfill at least 1 minor eligibility criteria; or Group 1C, decisions that did not fulfill at least 1 major eligibility criteria. Patient and clinical characteristics were tested for correlations with the availability of evidence. Of the 393 evaluable patients, malignancies of the breast (30%), head and neck (18%), and genitourinary system (14%) were the most common presenting primary disease sites. Forty-seven percent of all medical decisions (n = 451) were made without available (36%) or applicable (11%) randomized evidence to inform clinical decision making. Primary tumor diagnosis was significantly associated with the availability of evidence (P < .0001). A significant proportion of medical decisions in an academic radiation oncology clinic were made without available or applicable level I evidence, underscoring the limitations of relying solely on RCTs for the development of evidence-based health care. Copyright © 2013 American Cancer Society.

Recruitment, adherence, and retention of endometrial cancer survivors in a behavioural lifestyle programme: the Diet and Exercise in Uterine Cancer Survivors (DEUS) parallel randomised pilot trial.

PubMed

Koutoukidis, Dimitrios A; Beeken, Rebecca J; Manchanda, Ranjit; Michalopoulou, Moscho; Burnell, Matthew; Knobf, M Tish; Lanceley, Anne

2017-10-08

Healthy eating and physical activity may help endometrial cancer survivors (ECS) improve their quality of life. However, most ECS do not meet the relevant guidelines. This pilot trial aimed to test the study feasibility procedures for a definitive trial of a behavioural lifestyle programme. This 24-week parallel two-arm randomised pilot trial took place in two hospitals in London, UK (April 2015-June 2016). Sixty disease-free ECS within 3 years of diagnosis. Participants were randomised using minimisation to receive the intervention or care as usual. The 'Shape-Up following cancer treatment' programme used self-monitoring, goal-setting, self-incentives, problem-solving and group social support for 12 hours over 8 weeks to help survivors improve their eating and physical activity. The main outcome measures were recruitment, adherence, and retention rates. Further outcomes included barriers to participation and feedback on programme satisfaction. Of the 296 potentially eligible ECS, 20% (n=60) were randomly allocated to the active intervention (n=29) or control group (n=31). Three participants in each arm were deemed ineligible after randomisation and excluded from analysis. Twenty participants (77%; 95% CI 61% to 93%) adhered to the intervention and provided generally favourable feedback. At 24 weeks, 25/26 (96%; 95% CI 89% to 100%) intervention and 24/28 (86%; 95% CI 73% to 99%) control participants completed their assessment. No intervention-related adverse events were reported. Among eligible survivors who declined study participation (n=83), inconvenience (78%; 95% CI 69% to 87%) was the most common barrier. The trial was feasible to deliver based on the a priori feasibility criteria. Enhancing recruitment and adherence in a definitive trial will require designs that promote convenience and consider ECS-reported barriers. NCT02433080; Pre-results. University College London, St. Bartholomew's Hospital Nurses League, and NIHR University College London Hospitals Biomedical Research Centre. © 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.

An online randomized controlled trial, with or without problem-solving treatment, for long-term cancer survivors after hematopoietic cell transplantation.

PubMed

Syrjala, Karen L; Yi, Jean C; Artherholt, Samantha B; Romano, Joan M; Crouch, Marie-Laure; Fiscalini, Allison S; Hegel, Mark T; Flowers, Mary E D; Martin, Paul J; Leisenring, Wendy M

2018-05-05

This randomized controlled trial examines the efficacy of INSPIRE, an INternet-based Survivorship Program with Information and REsources, with or without problem-solving treatment (PST) telehealth calls, for survivors after hematopoietic cell transplantation (HCT). All adult survivors who met eligibility criteria were approached for consent. Participants completed patient-reported outcomes at baseline and 6 months. Those with baseline impaired scores on one or more of the outcomes were randomized to INSPIRE, INSPIRE + PST, or control with delayed INSPIRE access. Outcomes included Cancer and Treatment Distress, Symptom Checklist-90-R Depression, and Fatigue Symptom Inventory. Planned analyses compared arms for mean change in aggregated impaired outcomes and for proportion of participants improved on each outcome. Of 1306 eligible HCT recipients, 755 (58%) participated, and 344 (45%) had one or more impaired scores at baseline. We found no reduction in aggregated outcomes for either intervention (P > 0.3). In analyses of individual outcomes, participants randomized to INSPIRE + PST were more likely to improve in distress than controls (45 vs. 20%, RR 2.3, CI 1.0, 5.1); those randomized to INSPIRE alone were marginally more likely to improve in distress (40 vs. 20%, RR 2.0, CI 0.9, 4.5). The INSPIRE online intervention demonstrated a marginal benefit for distress that improved with the addition of telehealth PST, particularly for those who viewed the website or were age 40 or older. Online and telehealth programs such as INSPIRE offer opportunities to enhance HCT survivorship outcomes, particularly for mood, though methods would benefit from strategies to improve efficacy.

Clinical Trials Targeting Aging and Age-Related Multimorbidity

PubMed Central

Crimmins, Eileen M; Grossardt, Brandon R; Crandall, Jill P; Gelfond, Jonathan A L; Harris, Tamara B; Kritchevsky, Stephen B; Manson, JoAnn E; Robinson, Jennifer G; Rocca, Walter A; Temprosa, Marinella; Thomas, Fridtjof; Wallace, Robert; Barzilai, Nir

2017-01-01

Abstract Background There is growing interest in identifying interventions that may increase health span by targeting biological processes underlying aging. The design of efficient and rigorous clinical trials to assess these interventions requires careful consideration of eligibility criteria, outcomes, sample size, and monitoring plans. Methods Experienced geriatrics researchers and clinical trialists collaborated to provide advice on clinical trial design. Results Outcomes based on the accumulation and incidence of age-related chronic diseases are attractive for clinical trials targeting aging. Accumulation and incidence rates of multimorbidity outcomes were developed by selecting at-risk subsets of individuals from three large cohort studies of older individuals. These provide representative benchmark data for decisions on eligibility, duration, and assessment protocols. Monitoring rules should be sensitive to targeting aging-related, rather than disease-specific, outcomes. Conclusions Clinical trials targeting aging are feasible, but require careful design consideration and monitoring rules. PMID:28364543

Automated clinical trial eligibility prescreening: increasing the efficiency of patient identification for clinical trials in the emergency department

PubMed Central

Ni, Yizhao; Kennebeck, Stephanie; Dexheimer, Judith W; McAneney, Constance M; Tang, Huaxiu; Lingren, Todd; Li, Qi; Zhai, Haijun; Solti, Imre

2015-01-01

Objectives (1) To develop an automated eligibility screening (ES) approach for clinical trials in an urban tertiary care pediatric emergency department (ED); (2) to assess the effectiveness of natural language processing (NLP), information extraction (IE), and machine learning (ML) techniques on real-world clinical data and trials. Data and methods We collected eligibility criteria for 13 randomly selected, disease-specific clinical trials actively enrolling patients between January 1, 2010 and August 31, 2012. In parallel, we retrospectively selected data fields including demographics, laboratory data, and clinical notes from the electronic health record (EHR) to represent profiles of all 202795 patients visiting the ED during the same period. Leveraging NLP, IE, and ML technologies, the automated ES algorithms identified patients whose profiles matched the trial criteria to reduce the pool of candidates for staff screening. The performance was validated on both a physician-generated gold standard of trial–patient matches and a reference standard of historical trial–patient enrollment decisions, where workload, mean average precision (MAP), and recall were assessed. Results Compared with the case without automation, the workload with automated ES was reduced by 92% on the gold standard set, with a MAP of 62.9%. The automated ES achieved a 450% increase in trial screening efficiency. The findings on the gold standard set were confirmed by large-scale evaluation on the reference set of trial–patient matches. Discussion and conclusion By exploiting the text of trial criteria and the content of EHRs, we demonstrated that NLP-, IE-, and ML-based automated ES could successfully identify patients for clinical trials. PMID:25030032

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.

The effect of intensive glucose control on all-cause and cardiovascular mortality, myocardial infarction and stroke in persons with type 2 diabetes mellitus: a systematic review and meta-analysis.

PubMed

Marso, Steven P; Kennedy, Kevin F; House, John A; McGuire, Darren K

2010-04-01

We performed a meta-analysis of studies evaluating the effect of intensive glucose control on major adverse cardiovascular events in patients with type 2 diabetes from 1990 to 2009. A search of the published literature and the Cochran Central Register for Controlled Trials was performed using pre-specified inclusion criteria consisting of randomised controlled trials evaluating intensive glycaemic control and reporting the individual endpoints of all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke. Incident rate ratios for these endpoints were calculated using standard meta-analytic techniques of pooled data from eligible trials. Six reports from four randomised trials including 27,544 patients met the pre-specified inclusion criteria. Mean follow-up was 5.4 years; haemoglobin A(1C) at study end was 6.6% vs. 7.4% in patients randomised to intensive compared with conventional glucose control. Intensive glucose control did not affect the incident rate ratio for all-cause mortality (1.01, 95% confidence interval 0.86-1.18, p=0.54) or stroke (1.02, 95% confidence interval 0.88-1.20, p=0.62). However, there was a statistically significant 14% reduction in non-fatal myocardial infarction in patients randomised to intensive glucose control (0.86, 95% confidence interval 0.77-0.97, p=0.015). Although intensification of glucose control did not affect mortality or non-fatal stroke, the risk for non-fatal myocardial infarction was significantly reduced in patients with type 2 diabetes.

The effect of a therapeutic regimen of Traditional Chinese Medicine rehabilitation for post-stroke cognitive impairment: study protocol for a randomized controlled trial.

PubMed

Huang, Jia; Lin, Zhengkun; Wang, Qin; Liu, Feiwen; Liu, Jiao; Fang, Yunhua; Chen, Shanjia; Zhou, Xiaoxuan; Hong, Wenjun; Wu, Jinsong; Madrigal-Mora, Natalia; Zheng, Guohua; Yang, Shanli; Tao, Jing; Chen, Lidian

2015-06-16

Post-stroke cognitive impairment (PSCI) lessens quality of life, restricts the rehabilitation of stroke, and increases the social and economic burden stroke imposes on patients and their families. Therefore effective treatment is of paramount importance. However, the treatment of PSCI is very limited. The primary aim of this protocol is to propose a lower cost and more effective therapy, and to confirm the long-term effectiveness of a therapeutic regimen of Traditional Chinese Medicine (TCM) rehabilitation for PSCI. A prospective, multicenter, large sample, randomized controlled trial will be conducted. A total of 416 eligible patients will be recruited from seven inpatient and outpatient stroke rehabilitation units and randomly allocated into a therapeutic regimen of TCM rehabilitation group or cognitive training (CT) control group. The intervention period of both groups will last 12 weeks (30 minutes per day, five days per week). Primary and secondary outcomes will be measured at baseline, 12 weeks (at the end of the intervention), and 36 weeks (after the 24-week follow-up period). This protocol presents an objective design of a multicenter, large sample, randomized controlled trial that aims to put forward a lower cost and more effective therapy, and confirm the long-term effectiveness of a therapeutic regimen of TCM rehabilitation for PSCI through subjective and objective assessments, as well as highlight its economic advantages. This trial was registered with the Chinese Clinical Trial Registry (identifier: ChiCTR-TRC-14004872 ) on 23 June 2014.

Mobile Phone Intervention and Weight Loss Among Overweight and Obese Adults: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Liu, Fangchao; Kong, Xiaomu; Cao, Jie; Chen, Shufeng; Li, Changwei; Huang, Jianfeng; Gu, Dongfeng; Kelly, Tanika N.

2015-01-01

We conducted a meta-analysis of randomized controlled trials to examine the association of mobile phone intervention with net change in weight-related measures among overweight and obese adults. We searched electronic databases and conducted a bibliography review to identify articles published between the inception date of each database and March 27, 2014. Fourteen trials (including 1,337 participants in total) that met the eligibility criteria were included. Two investigators independently abstracted information on study characteristics and study outcomes. Net change estimates comparing the intervention group with the control group were pooled across trials using random-effects models. Compared with the control group, mobile phone intervention was associated with significant changes in body weight and body mass index (weight (kg)/height (m)2) of −1.44 kg (95% confidence interval (CI): −2.12, −0.76) and −0.24 units (95% CI: −0.40, −0.08), respectively. Subgroup analyses revealed that the associations were consistent across study-duration and intervention-type subgroups. For example, net body weight changes were −0.92 kg (95% CI: −1.58, −0.25) and −1.85 kg (95% CI: −2.99, −0.71) in trials of shorter (<6 months) and longer (≥6 months) duration, respectively. These findings provide evidence that mobile phone intervention may be a useful tool for promoting weight loss among overweight and obese adults. PMID:25673817

Home-based neurologic music therapy for arm hemiparesis following stroke: results from a pilot, feasibility randomized controlled trial.

PubMed

Street, Alexander J; Magee, Wendy L; Bateman, Andrew; Parker, Michael; Odell-Miller, Helen; Fachner, Jorg

2018-01-01

To assess the feasibility of a randomized controlled trial to evaluate music therapy as a home-based intervention for arm hemiparesis in stroke. A pilot feasibility randomized controlled trial, with cross-over design. Randomization by statistician using computer-generated, random numbers concealed in opaque envelopes. Participants' homes across Cambridgeshire, UK. Eleven people with stroke and arm hemiparesis, 3-60 months post stroke, following discharge from community rehabilitation. Each participant engaged in therapeutic instrumental music performance in 12 individual clinical contacts, twice weekly for six weeks. Feasibility was estimated by recruitment from three community stroke teams over a 12-month period, attrition rates, completion of treatment and successful data collection. Structured interviews were conducted pre and post intervention to establish participant tolerance and preference. Action Research Arm Test and Nine-hole Peg Test data were collected at weeks 1, 6, 9, 15 and 18, pre and post intervention by a blinded assessor. A total of 11 of 14 invited participants were recruited (intervention n = 6, waitlist n = 5). In total, 10 completed treatment and data collection. It cannot be concluded whether a larger trial would be feasible due to unavailable data regarding a number of eligible patients screened. Adherence to treatment, retention and interview responses might suggest that the intervention was motivating for participants. ClinicalTrials.gov identifier NCT 02310438.

The Indiana Chronic Disease Management Program

PubMed Central

Rosenman, Marc B; Holmes, Ann M; Ackermann, Ronald T; Murray, Michael D; Doebbeling, Caroline Carney; Katz, Barry; Li, Jingjin; Zillich, Alan; Prescott, Victoria M; Downs, Stephen M; Inui, Thomas S

2006-01-01

The Indiana Chronic Disease Management Program (ICDMP) is intended to improve the quality and cost-effectiveness of care for Medicaid members with congestive heart failure (chronic heart failure), diabetes, asthma, and other conditions. The ICDMP is being assembled by Indiana Medicaid primarily from state and local resources and has seven components: (1) identification of eligible participants to create regional registries, (2) risk stratification of eligible participants, (3) nurse care management for high-risk participants, (4) telephonic intervention for all participants, (5) an Internet-based information system, (6) quality improvement collaboratives for primary care practices, and (7) program evaluation. The evaluation involves a randomized controlled trial in two inner-city group practices, as well as a statewide observational design. This article describes the ICDMP, highlights challenges, and discusses approaches to its evaluation. PMID:16529571

The Indiana Chronic Disease Management Program.

PubMed

Rosenman, Marc B; Holmes, Ann M; Ackermann, Ronald T; Murray, Michael D; Doebbeling, Caroline Carney; Katz, Barry; Li, Jingjin; Zillich, Alan; Prescott, Victoria M; Downs, Stephen M; Inui, Thomas S

2006-01-01

The Indiana Chronic Disease Management Program (ICDMP) is intended to improve the quality and cost-effectiveness of care for Medicaid members with congestive heart failure (chronic heart failure), diabetes, asthma, and other conditions. The ICDMP is being assembled by Indiana Medicaid primarily from state and local resources and has seven components: (1) identification of eligible participants to create regional registries, (2) risk stratification of eligible participants, (3) nurse care management for high-risk participants, (4) telephonic intervention for all participants, (5) an Internet-based information system, (6) quality improvement collaboratives for primary care practices, and (7) program evaluation. The evaluation involves a randomized controlled trial in two inner-city group practices, as well as a statewide observational design. This article describes the ICDMP, highlights challenges, and discusses approaches to its evaluation.

Effect of fermented milk-based probiotic preparations on Helicobacter pylori eradication: a systematic review and meta-analysis of randomized-controlled trials.

PubMed

Sachdeva, Aarti; Nagpal, Jitender

2009-01-01

To evaluate the effect of fermented milk-based probiotic preparations on Helicobacter pylori eradication. Systematic review of randomized controlled trials. Electronic databases and hand search of reviews, bibliographies of books and abstracts and proceedings of international conferences. Included trials had to be randomized or quasi-randomized and controlled, using fermented milk-based probiotics in the intervention group, treating Helicobacter-infected patients and evaluating improvement or eradication of H. pylori as an outcome. The search identified 10 eligible randomized controlled trials. Data were available for 963 patients, of whom 498 were in the treatment group and 465 in the control group. The pooled odds ratio (studies n=9) for eradication by intention-to-treat analysis in the treatment versus control group was 1.91 (1.38-2.67; P<0.0001) using the fixed effects model; test for heterogeneity (Cochran's Q=5.44; P=0.488). The pooled risk difference was 0.10 (95% CI 0.05-0.15; P<0.0001) by the fixed effects model (Cochran's Q=13.41; P=0.144). The pooled odds ratio for the number of patients with any adverse effect was 0.51 (95% CI 0.10-2.57; P=0.41; random effects model; heterogeneity by Cochran's Q=68.5; P<0.0001). Fermented milk-based probiotic preparations improve H. pylori eradication rates by approximately 5-15%, whereas the effect on adverse effects is heterogeneous.

Comparing open and minimally invasive surgical procedures for oesophagectomy in the treatment of cancer: the ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) feasibility study and pilot trial.

PubMed

Metcalfe, Chris; Avery, Kerry; Berrisford, Richard; Barham, Paul; Noble, Sian M; Fernandez, Aida Moure; Hanna, George; Goldin, Robert; Elliott, Jackie; Wheatley, Timothy; Sanders, Grant; Hollowood, Andrew; Falk, Stephen; Titcomb, Dan; Streets, Christopher; Donovan, Jenny L; Blazeby, Jane M

2016-06-01

Localised oesophageal cancer can be curatively treated with surgery (oesophagectomy) but the procedure is complex with a risk of complications, negative effects on quality of life and a recovery period of 6-9 months. Minimal-access surgery may accelerate recovery. The ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) study aimed to establish the feasibility of, and methodology for, a definitive trial comparing minimally invasive and open surgery for oesophagectomy. Objectives were to quantify the number of eligible patients in a pilot trial; develop surgical manuals as the basis for quality assurance; standardise pathological processing; establish a method to blind patients to their allocation in the first week post surgery; identify measures of postsurgical outcome of importance to patients and clinicians; and establish the main cost differences between the surgical approaches. Pilot parallel three-arm randomised controlled trial nested within feasibility work. Two UK NHS departments of upper gastrointestinal surgery. Patients aged ≥ 18 years with histopathological evidence of oesophageal or oesophagogastric junctional adenocarcinoma, squamous cell cancer or high-grade dysplasia, referred for oesophagectomy or oesophagectomy following neoadjuvant chemo(radio)therapy. Oesophagectomy, with patients randomised to open surgery, a hybrid open chest and minimally invasive abdomen or totally minimally invasive access. The primary outcome measure for the pilot trial was the number of patients recruited per month, with the main trial considered feasible if at least 2.5 patients per month were recruited. During 21 months of recruitment, 263 patients were assessed for eligibility; of these, 135 (51%) were found to be eligible and 104 (77%) agreed to participate, an average of five patients per month. In total, 41 patients were allocated to open surgery, 43 to the hybrid procedure and 20 to totally minimally invasive surgery. Recruitment is continuing, allowing a seamless transition into the definitive trial. Consequently, the database is unlocked at the time of writing and data presented here are for patients recruited by 31 August 2014. Random allocation achieved a good balance between the arms of the study, which, as a high proportion of patients underwent their allocated surgery (69/79, 87%), ensured a fair comparison between the interventions. Dressing patients with large bandages, covering all possible incisions, was successful in keeping patients blind while pain was assessed during the first week post surgery. Postsurgical length of stay and risk of adverse events were within the typical range for this group of patients, with one death occurring within 30 days among 76 patients. There were good completion rates for the assessment of pain at 6 days post surgery (88%) and of the patient-reported outcomes at 6 weeks post randomisation (74%). Rapid recruitment to the pilot trial and the successful refinement of methodology indicated the feasibility of a definitive trial comparing different approaches to oesophagectomy. Although we have shown a full trial of open compared with minimally invasive oesophagectomy to be feasible, this is necessarily based on our findings from the two clinical centres that we could include in this small preliminary study. Current Controlled Trials ISRCTN59036820. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 48. See the NIHR Journals Library website for further project information.

Effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression: A systematic review of systematic reviews and meta-analyses.

PubMed

Bellón, Juan Ángel; Moreno-Peral, Patricia; Motrico, Emma; Rodríguez-Morejón, Alberto; Fernández, Ana; Serrano-Blanco, Antoni; Zabaleta-del-Olmo, Edurne; Conejo-Cerón, Sonia

2015-07-01

To determine the effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression. Systematic review of systematic reviews and meta-analyses (SR/MA). We searched PubMed, PsycINFO, Cochrane Database of Systematic Reviews, OpenGrey, and PROSPERO from their inception until February 2014. Two reviewers independently evaluated the eligibility criteria of all SR/MA, abstracted data, and determined bias risk (AMSTAR). Twelve SR/MA (156 non-repeated trials and 56,158 participants) were included. Of these, 142 (91%) were randomized-controlled, 13 (8.3%) controlled trials, and 1 (0.6%) had no control group. Five SR/MA focused on children and adolescents, four on specific populations (women after childbirth, of low socioeconomic status, or unfavorable circumstances; patients with severe traumatic physical injuries or stroke) and three addressed the general population. Nine (75%) SR/MA concluded that interventions to prevent depression were effective. Of the 156 trials, 137 (87.8%) reported some kind of effect size calculation. Effect sizes were small in 45 (32.8%), medium in 26 (19.1%), and large in 25 (18.2%) trials; 41 (29.9%) trials were not effective. Of the 141 trials for which follow-up periods were available, only 34 (24.1%) exceeded 12 months. Psychological and/or educational interventions to prevent onset of episodes of depression were effective, although most had small or medium effect sizes. Copyright © 2014. Published by Elsevier Inc.

Home-based neurologic music therapy for arm hemiparesis following stroke: results from a pilot, feasibility randomized controlled trial

PubMed Central

Street, Alexander J; Magee, Wendy L; Bateman, Andrew; Parker, Michael; Odell-Miller, Helen; Fachner, Jorg

2017-01-01

Objective: To assess the feasibility of a randomized controlled trial to evaluate music therapy as a home-based intervention for arm hemiparesis in stroke. Design: A pilot feasibility randomized controlled trial, with cross-over design. Randomization by statistician using computer-generated, random numbers concealed in opaque envelopes. Setting: Participants’ homes across Cambridgeshire, UK. Subjects: Eleven people with stroke and arm hemiparesis, 3–60 months post stroke, following discharge from community rehabilitation. Interventions: Each participant engaged in therapeutic instrumental music performance in 12 individual clinical contacts, twice weekly for six weeks. Main measures: Feasibility was estimated by recruitment from three community stroke teams over a 12-month period, attrition rates, completion of treatment and successful data collection. Structured interviews were conducted pre and post intervention to establish participant tolerance and preference. Action Research Arm Test and Nine-hole Peg Test data were collected at weeks 1, 6, 9, 15 and 18, pre and post intervention by a blinded assessor. Results: A total of 11 of 14 invited participants were recruited (intervention n = 6, waitlist n = 5). In total, 10 completed treatment and data collection. Conclusion: It cannot be concluded whether a larger trial would be feasible due to unavailable data regarding a number of eligible patients screened. Adherence to treatment, retention and interview responses might suggest that the intervention was motivating for participants. Trial registration: ClinicalTrials.gov identifier NCT 02310438. PMID:28643570

Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE).

PubMed

Duceppe, Emmanuelle; Yusuf, Salim; Tandon, Vikas; Rodseth, Reitze; Biccard, Bruce M; Xavier, Denis; Szczeklik, Wojciech; Meyhoff, Christian S; Franzosi, Maria Grazia; Vincent, Jessica; Srinathan, Sadeesh K; Parlow, Joel; Magloire, Patrick; Neary, John; Rao, Mangala; Chaudhry, Navneet K; Mayosi, Bongani; de Nadal, Miriam; Popova, Ekaterine; Villar, Juan Carlos; Botto, Fernando; Berwanger, Otavio; Guyatt, Gordon; Eikelboom, John W; Sessler, Daniel I; Kearon, Clive; Pettit, Shirley; Connolly, Stuart J; Sharma, Mukul; Bangdiwala, Shrikant I; Devereaux, P J

2018-03-01

Worldwide approximately 200 million adults undergo major surgery annually, of whom 8 million are estimated to suffer a myocardial injury after noncardiac surgery (MINS). There is currently no trial data informing the management of MINS. Antithrombotic agents such as direct oral anticoagulants might prevent major vascular complications in patients with MINS. The Management of Myocardial Injury After Noncardiac Surgery (MANAGE) trial is a large international blinded randomized controlled trial of dabigatran vs placebo in patients who suffered MINS. We used a partial factorial design to also determine the effect of omeprazole vs placebo in reducing upper gastrointestinal bleeding and complications. Both study drugs were initiated in eligible patients within 35 days of suffering MINS and continued for a maximum of 2 years. The primary outcome is a composite of major vascular complications for the dabigatran trial and a composite of upper gastrointestinal complications for the omeprazole trial. We present the rationale and design of the trial and baseline characteristics of enrolled patients. The trial randomized 1754 patients between January 2013 and July 2017. Patients' mean age was 69.9 years, 51.1% were male, 14.3% had a history of peripheral artery disease, 6.6% had a history of stroke or transient ischemic attack, 12.9% had a previous myocardial infarction, and 26.0% had diabetes. The diagnosis of MINS was on the basis of an isolated ischemic troponin elevation in 80.4% of participants. MANAGE is the first randomized controlled trial to evaluate a potential treatment of patients who suffered MINS. Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

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

Antimicrobial drugs for persistent diarrhoea of unknown or non-specific cause in children under six in low and middle income countries: systematic review of randomized controlled trials

PubMed Central

2009-01-01

Background A high proportion of children with persistent diarrhoea in middle and low income countries die. The best treatment is not clear. We conducted a systematic review to evaluate the effectiveness of antimicrobial drug treatment for persistent diarrhoea of unknown or non-specific cause. Methods We included randomized comparisons of antimicrobial drugs for the treatment of persistent diarrhoea of unknown or non-specific cause in children under the age of six years in low and middle income countries. We searched the electronic databases MEDLINE, EMBASE, LILACS, WEB OF SCIENCE, and the Cochrane Central Register of Controlled Trials (CENTRAL) to May 2008 for relevant randomized or quasi randomized controlled trials. We summarised the characteristics of the eligible trials, assessed their quality using standard criteria, and extracted relevant outcomes data. Where appropriate, we combined the results of different trials. Results Three trials from South East Asia and one from Guatemala were included, all were small, and three had adequate allocation concealment. Two were in patients with diarrhoea of unknown cause, and two were in patients in whom known bacterial or parasitological causes of diarrhoea had been excluded. No difference was demonstrated for oral gentamicin compared with placebo (presence of diarrhoea at 6 or 7 days; 2 trials, n = 151); and for metronidazole compared with placebo (presence of diarrhoea at 3, 5 and 7 days; 1 trial, n = 99). In one small trial, sulphamethoxazole-trimethoprim appeared better than placebo in relation to diarrhoea at seven days and total stool volume (n = 55). Conclusion There is little evidence as to whether or not antimicrobials help treat persistent diarrhoea in young children in low and middle income countries. PMID:19257885

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

PubMed

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

2012-08-15

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

Recruitment strategies for a possible tamoxifen trial.

PubMed

Kuller, L H

1991-01-01

Participants in a primary prevention trial using tamoxifen to prevent breast cancer should comprise a sample of (a) age-eligible women from the "general population," (b) higher risk sisters of breast cancer patients, (c) women participating in mammography screening programs, or (d) patients of (or other users of) primary care physicians' offices. The recruitment should consider the risk of breast cancer among eligible women, likelihood of adherence to protocol, and unbiased and accurate measurement of endpoints. The Risks for coronary heart disease, hypertension, diabetes, osteoporosis, and other cancers, especially uterine cancer, must also be evaluated. Recruitment is feasible and should not be the limiting factor in the decision to undertake a primary prevention trial.

Tissue adhesives for closure of surgical incisions.

PubMed

Dumville, Jo C; Coulthard, Paul; Worthington, Helen V; Riley, Philip; Patel, Neil; Darcey, James; Esposito, Marco; van der Elst, Maarten; van Waes, Oscar J F

2014-11-28

Sutures (stitches), staples and adhesive tapes have been used for many years as methods of wound closure, but tissue adhesives have entered clinical practice more recently. Closure of wounds with sutures enables the closure to be meticulous, but the sutures may show tissue reactivity and can require removal. Tissue adhesives offer the advantages of an absence of risk of needlestick injury and no requirement to remove sutures later. Initially, tissue adhesives were used primarily in emergency room settings, but this review looks at the use of tissue adhesives in the operating room/theatre where surgeons are using them increasingly for the closure of surgical skin incisions. To determine the effects of various tissue adhesives compared with conventional skin closure techniques for the closure of surgical wounds. In March 2014 for this second update we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. We did not restrict the search and study selection with respect to language, date of publication or study setting. Only randomised controlled trials were eligible for inclusion. We conducted screening of eligible studies, data extraction and risk of bias assessment independently and in duplicate. We expressed results as random-effects models using mean difference for continuous outcomes and risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes. We investigated heterogeneity, including both clinical and methodological factors. This second update of the review identified 19 additional eligible trials resulting in a total of 33 studies (2793 participants) that met the inclusion criteria. There was low quality evidence that sutures were significantly better than tissue adhesives for reducing the risk of wound breakdown (dehiscence; RR 3.35; 95% CI 1.53 to 7.33; 10 trials, 736 participants that contributed data to the meta-analysis). The number needed to treat for an additional harmful outcome was calculated as 43. For all other outcomes - infection, patient and operator satisfaction and cost - there was no evidence of a difference for either sutures or tissue adhesives. No evidence of differences was found between tissue adhesives and tapes for minimising dehiscence, infection, patients' assessment of cosmetic appearance, patient satisfaction or surgeon satisfaction. However there was evidence in favour of using tape for surgeons' assessment of cosmetic appearance (mean difference (VAS 0 to 100) 9.56 (95% CI 4.74 to 14.37; 2 trials, 139 participants). One trial compared tissue adhesives with a variety of methods of wound closure and found both patients and clinicians were significantly more satisfied with the alternative closure methods than the adhesives. There appeared to be little difference in outcome for different types of tissue adhesives. One study that compared high viscosity with low viscosity adhesives found that high viscosity adhesives were less time-consuming to use than low viscosity tissue adhesives, but the time difference was small. Sutures are significantly better than tissue adhesives for minimising dehiscence. In some cases tissue adhesives may be quicker to apply than sutures. Although surgeons may consider the use of tissue adhesives as an alternative to other methods of surgical site closure in the operating theatre, they need to be aware that sutures minimise dehiscence. There is a need for more well designed randomised controlled trials comparing tissue adhesives with alternative methods of closure. These trials should include people whose health may interfere with wound healing and surgical sites of high tension.

Effectiveness of Chinese massage therapy (Tui Na) for chronic low back pain: study protocol for a randomized controlled trial.

PubMed

Yang, Mingxiao; Feng, Yue; Pei, Hong; Deng, Shufang; Wang, Minyu; Xiao, Xianjun; Zheng, Hui; Lai, Zhenhong; Chen, Jiao; Li, Xiang; He, Xiaoguo; Liang, Fanrong

2014-10-29

Low back pain is a common, disabling musculoskeletal disorder in both developing and developed countries. Although often recommended, the potential efficacy of massage therapy in general, and Chinese massage (tuina) in particular, for relief of chronic low back pain (CLBP) has not been fully established due to inadequate sample sizes, low methodological quality, and subclinical dosing regimens of trials to date. Thus, the purpose of this randomized controlled trial (RCT) is to evaluate the comparative effectiveness of tuina massage therapy versus conventional analgesics for CLBP. The present study is a single center, two-arm, open-label RCT. A total of 150 eligible CLBP patients will be randomly assigned to either a tuina treatment group or a conventional drug control group in a 1:1 ratio. Patients in the tuina group receive a 20 minutes, 4-step treatment protocol which includes both structural and relaxation massage, administered in 20 sessions over a period of 4 weeks. Patients in the conventional drug control group are instructed to take a specific daily dose of ibuprofen. The primary outcome measure is the change from baseline back pain and function, measured by Roland-Morris Disability Questionnaire, at two months. Secondary outcome measures include the visual analogue scale, Japanese orthopedic association score (JOAS), and McGill pain questionnaire. The design and methodological rigor of this trial will allow for collection of valuable data to evaluate the efficacy of a specific tuina protocol for treating CLBP. This trial will therefore contribute to providing a solid foundation for clinical treatment of CLBP, as well as future research in massage therapy. This trial was registered with ClinicalTrials.gov of the National Institute of Health on 22 October 2013 (http://NCT01973010).

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.

Protocol for a randomised, placebo-controlled pilot study for assessing feasibility and efficacy of faecal microbiota transplantation in a paediatric ulcerative colitis population: PediFETCh trial

PubMed Central

Popov, Jelena

2017-01-01

Introduction Ulcerative colitis (UC) is a chronic, relapsing condition characterised by colonic inflammation. Increasing prevalence in early-age diagnosis provides opportunities for additional complications in later life as a result of prolonged exposure to inflammatory and therapeutic insults, necessitating novel avenues for therapeutics which may result in fewer side effects. Faecal microbiota transplantation (FMT) has previously demonstrated potential therapeutic benefit in an adult randomised-controlled trial and several recurrent Clostridium difficile infection studies. This phase Ib pilot will be the first randomised, single-blinded, placebo-controlled trial to assess feasibility and patient outcomes in a paediatric inflammatory bowel disease (IBD) population. Methods and analysis Fifty patients will be randomised 1:1 to receive normal saline control or active sample. Enema administrations will be performed two times per week for 6 weeks, followed at a 6-month follow-up period. Feasibility outcomes will include measures of patient eligibility, recruitment, willingness to participate, samples collections, hospitalizations and drop-out rate. Improvements in disease symptoms will determine the efficacy of treatment. Clinical disease scores will be taken throughout the study period using the Paediatric Ulcerative Colitis Activity Index (PUCAI). Monitoring of inflammatory markers in blood and stool will be performed at regular intervals. Microbiome analysis will be conducted on stool samples collected throughout the trials period. Imaging and endoscopic surveillance will be conducted if clinically necessary. Ethics and dissemination Ethics was obtained from local hospital research ethics boards across all three sites. Health Canada and FDA approval was obtained for the use of an Investigatory New Drug product. Results from this trial will be presented in international conferences and published in peer-review journals. Trial registration number Trial registration number: NCT02487238; preresults. PMID:28827258

EARLYDRAIN- outcome after early lumbar CSF-drainage in aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial.

PubMed

Bardutzky, Jürgen; Witsch, Jens; Jüttler, Eric; Schwab, Stefan; Vajkoczy, Peter; Wolf, Stefan

2011-09-14

Aneurysmal subarachnoid hemorrhage (SAH) may be complicated by delayed cerebral ischemia, which is a major cause of unfavorable clinical outcome and death in SAH-patients. Delayed cerebral ischemia is presumably related to the development of vasospasm triggered by the presence of blood in the basal cisterns. To date, oral application of the calcium antagonist nimodipine is the only prophylactic treatment for vasospasm recognized under international guidelines.In retrospective trials lumbar drainage of cerebrospinal fluid has been shown to be a safe and feasible measure to remove the blood from the basal cisterns and decrease the incidence of delayed cerebral ischemia and vasospasm in the respective study populations. However, the efficacy of lumbar drainage has not been evaluated prospectively in a randomized controlled trial yet. This is a protocol for a 2-arm randomized controlled trial to compare an intervention group receiving early continuous lumbar CSF-drainage and standard neurointensive care to a control group receiving standard neurointensive care only. Adults suffering from a first aneurysmal subarachnoid hemorrhage whose aneurysm has been secured by means of coiling or clipping are eligible for trial participation. The effect of early CSF drainage (starting < 72 h after securing the aneurysm) will be measured in the following ways: the primary endpoint will be disability after 6 months, assessed by a blinded investigator during a personal visit or standardized telephone interview using the modified Rankin Scale. Secondary endpoints include mortality after 6 months, angiographic vasospasm, transcranial Doppler sonography (TCD) mean flow velocity in both middle cerebral arteries and rate of shunt insertion at 6 months after hospital discharge. Here, we present the study design of a multicenter prospective randomized controlled trial to investigate whether early application of a lumbar drainage improves clinical outcome after aneurysmal subarachnoid hemorrhage.

Effectiveness of alcohol brief intervention delivered by community pharmacists: study protocol of a two-arm randomised controlled trial

PubMed Central

2013-01-01

Background There is strong evidence to support the effectiveness of Brief Intervention (BI) in reducing alcohol consumption in primary healthcare. Methods and design This study is a two-arm randomised controlled trial to determine the effectiveness of BI delivered by community pharmacists in their pharmacies. Eligible and consenting participants (aged 18 years or older) will be randomised in equal numbers to either a BI delivered by 17 community pharmacists or a non-intervention control condition. The intervention will be a brief motivational discussion to support a reduction in alcohol consumption and will take approximately 10 minutes to deliver. Participants randomised to the control arm will be given an alcohol information leaflet with no opportunity for discussion. Study pharmacists will be volunteers who respond to an invitation to participate, sent to all community pharmacists in the London borough of Hammersmith and Fulham. Participating pharmacists will receive 7 hours training on trial procedures and the delivery of BI. Pharmacy support staff will also receive training (4 hours) on how to approach and inform pharmacy customers about the study, with formal trial recruitment undertaken by the pharmacist in a consultation room. At three month follow up, alcohol consumption and related problems will be assessed with the Alcohol Use Disorders Identification Test (AUDIT) administered by telephone. Discussion The UK Department of Health’s stated aim is to involve community pharmacists in the delivery of BI to reduce alcohol harms. This will be the first RCT study to assess the effectiveness of BI delivered by community pharmacists. Given this policy context, it is pragmatic in design. Trial registration Current Controlled Trials ISRCTN95216873 PMID:23419053

Laparoscopic techniques versus open techniques for inguinal hernia repair.

PubMed

McCormack, K; Scott, N W; Go, P M; Ross, S; Grant, A M

2003-01-01

Inguinal hernia repair is the most frequently performed operation in general surgery. The standard method for inguinal hernia repair had changed little over a hundred years until the introduction of synthetic mesh. This mesh can be placed by either using an open approach or by using a minimal access laparoscopic technique. Although many studies have explored the relative merits and potential risks of laparoscopic surgery for the repair of inguinal hernia, most individual trials have been too small to show clear benefits of one type of surgical repair over another. The objective of this review was to compare minimal access laparoscopic mesh techniques with open techniques. Comparisons of open mesh techniques versus open non-mesh techniques have been considered in a separate Cochrane review. We searched MEDLINE, EMBASE, and The Cochrane Central Controlled Trials Registry for relevant randomised controlled trials. The reference list of identified trials, journal supplements, relevant book chapters and conference proceedings were searched for further relevant trials. Through the EU Hernia Trialists Collaboration (EUHTC) communication took place with authors of identified randomised controlled trials to ask for information on any other recent and ongoing trials known to them. Specialists involved in research on the repair of inguinal hernia were contacted to ask for information about any further completed and ongoing trials. The world wide web was also searched. All published and unpublished randomised controlled trials and quasi-randomised controlled trials comparing laparoscopic groin hernia repair with open groin hernia repair were eligible for inclusion. Trials were included irrespective of the language in which they were reported. Individual patient data were obtained, where possible, from the responsible trialist for all eligible studies. All reanalyses were cross-checked by the reviewers and verified by the trialists before inclusion. Where IPD were unavailable additional aggregate data were sought from trialists and published aggregate data checked and verified by the trialists. IPD were available for 25 trials, additional aggregated data for seven and published data only for nine. Where possible, time to event analysis for hernia recurrence and return to usual activities were performed on an intention to treat principle. The main analyses were based on all trials. Sensitivity analyses based on the data source and trial quality were also performed. Pre-defined subgroup analyses based on recurrent hernias, bilateral hernias and femoral hernias were also carried out. 41 published reports of eligible trials were included involving 7161 participants. Sample sizes ranged from 38 to 994, with follow-up from 6 weeks to 36 months. Duration of operation was longer in the laparoscopic groups (WMD 14.81 minutes, 95% CI 13.98 to 15.64; p<0001). Operative complications were uncommon for both methods but more frequent in the laparoscopic group for visceral (Overall 8/2315 versus 1/2599) and vascular (Overall 7/2498 versus 5/2758) injuries. Length of hospital stay did not differ between groups (WMD -0.04 days, 95% CI -0.08 to 0.00; p=0.05, but return to usual activity was earlier for laparoscopic groups (HR 0.56, 95%CI 0.51 to 0.61; p<0.0001 - equivalent to 7 days). The data available showed less persisting pain (Overall 290/2101 versus 459/2399; Peto OR 0.54, 95% CI 0.46 to 0.64; p<0.0001), and less persisting numbness (Overall 102/1419 versus 217/1624; Peto OR 0.38, 95% CI 0.4286 to 0.49; p<0.0001) in the laparoscopic groups. In total, 86 recurrences were reported amongst 3138 allocated laparoscopic repair and 109 amongst 3504 allocated to open repair (Peto OR 0.81, 95% CI 0.61 to 1.08; p = 0.16). The use of mesh during laparoscopic hernia repair is associated with a reduction in the risk of hernia recurrence, significantly so for the transabdominal preperitoneal repair (TAPP) versus open non-mesh repair (overall 26/1440 versus preperitoneal repair (TAPP) versus open non-mesh repair (overall 26/1440 versus 47/1119; Peto OR 0.45, 95% CI 0.28 to 0.72; p=0.0009). However, no difference was detected when comparing laparoscopic methods with open mesh methods of hernia repair. The use of mesh during laparoscopic hernia repair is associated with a relative reduction in the risk of hernia recurrence of around 30-50%. However, there is no apparent difference in recurrence between laparoscopic and open mesh methods of hernia repair. The data suggests less persisting pain and numbness following laparoscopic repair. Return to usual activities is faster. However, operation times are longer and there appears to be a higher risk of serious complication rate in respect of visceral (especially bladder) and vascular injuries.

Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial

PubMed Central

Kahn, Susan R.; Shrier, Ian; Shapiro, Stan; Houweling, Adrielle H.; Hirsch, Andrew M.; Reid, Robert D.; Kearon, Clive; Rabhi, Khalil; Rodger, Marc A.; Kovacs, Michael J.; Anderson, David R.; Wells, Philip S.

2011-01-01

Background Exercise training may have the potential to improve post-thrombotic syndrome, a frequent, chronic complication of deep venous thrombosis. We conducted a randomized controlled two-centre pilot trial to assess the feasibility of a multicentre-based evaluation of a six-month exercise training program to treat post-thrombotic syndrome and to obtain preliminary data on the effectiveness of such a program. Methods Patients were randomized to receive exercise training (a six-month trainer-supervised program) or control treatment (an education session with monthly phone follow-ups). Levels of eligibility, consent, adherence and retention were used as indicators of study feasibility. Primary outcomes were change from baseline to six months in venous disease-specific quality of life (as measured using the Venous Insufficiency Epidemiological and Economic Study Quality of Life [VEINES-QOL] questionnaire) and severity of post-thrombotic syndrome (as measured by scores on the Villalta scale) in the exercise training group versus the control group, assessed by t tests. Secondary outcomes were change in generic quality of life (as measured using the Short-Form Health Survey-36 [SF-36] questionnaire), category of severity of post-thrombotic syndrome, leg strength, leg flexibility and time on treadmill. Results Of 95 patients with post-thrombotic syndrome, 69 were eligible, 43 consented and were randomized, and 39 completed the study. Exercise training was associated with improvement in VEINES-QOL scores (exercise training mean change 6.0, standard deviation [SD] 5.1 v. control mean change 1.4, SD 7.2; difference 4.6, 95% CI 0.54 to 8.7; p = 0.027) and improvement in scores on the Villalta scale (exercise training mean change −3.6, SD 3.7 v. control mean change −1.6, SD 4.3; difference −2.0, 95% CI −4.6 to 0.6; p = 0.14). Most secondary outcomes also showed greater improvement in the exercise training group. Interpretation Exercise training may improve post-thrombotic syndrome. It would be feasible to definitively evaluate exercise training as a treatment for post-thrombotic syndrome in a large multicentre trial. PMID:21098066

Effect of Replacing Animal Protein with Plant Protein on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Viguiliouk, Effie; Stewart, Sarah E.; Jayalath, Viranda H.; Ng, Alena Praneet; Mirrahimi, Arash; de Souza, Russell J.; Hanley, Anthony J.; Bazinet, Richard P.; Blanco Mejia, Sonia; Leiter, Lawrence A.; Josse, Robert G.; Kendall, Cyril W.C.; Jenkins, David J.A.; Sievenpiper, John L.

2015-01-01

Previous research on the effect of replacing sources of animal protein with plant protein on glycemic control has been inconsistent. We therefore conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of this replacement on glycemic control in individuals with diabetes. We searched MEDLINE, EMBASE, and Cochrane databases through 26 August 2015. We included RCTs ≥ 3-weeks comparing the effect of replacing animal with plant protein on HbA1c, fasting glucose (FG), and fasting insulin (FI). Two independent reviewers extracted relevant data, assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q-statistic) and quantified (I2-statistic). Thirteen RCTs (n = 280) met the eligibility criteria. Diets emphasizing a replacement of animal with plant protein at a median level of ~35% of total protein per day significantly lowered HbA1c (MD = −0.15%; 95%-CI: −0.26, −0.05%), FG (MD = −0.53 mmol/L; 95%-CI: −0.92, −0.13 mmol/L) and FI (MD = −10.09 pmol/L; 95%-CI: −17.31, −2.86 pmol/L) compared with control arms. Overall, the results indicate that replacing sources of animal with plant protein leads to modest improvements in glycemic control in individuals with diabetes. Owing to uncertainties in our analyses there is a need for larger, longer, higher quality trials. Trial Registration: ClinicalTrials.gov registration number: NCT02037321. PMID:26633472

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

Stress management versus lifestyle modification on systolic hypertension and medication elimination: a randomized trial.

PubMed

Dusek, Jeffery A; Hibberd, Patricia L; Buczynski, Beverly; Chang, Bei-Hung; Dusek, Kathryn C; Johnston, Jennifer M; Wohlhueter, Ann L; Benson, Herbert; Zusman, Randall M

2008-03-01

Isolated systolic hypertension is common in the elderly, but decreasing systolic blood pressure (SBP) without lowering diastolic blood pressure (DBP) remains a therapeutic challenge. Although stress management training, in particular eliciting the relaxation response, reduces essential hypertension its efficacy in treating isolated systolic hypertension has not been evaluated. We conducted a double-blind, randomized trial comparing 8 weeks of stress management, specifically relaxation response training (61 patients), versus lifestyle modification (control, 61 patients). Inclusion criteria were >or=55 years, SBP 140-159 mm Hg, DBP <90 mm Hg, and at least two antihypertensive medications. The primary outcome measure was change in SBP after 8 weeks. Patients who achieved SBP <140 mm Hg and >or=5 mm Hg reduction in SBP were eligible for 8 additional weeks of training with supervised medication elimination. SBP decreased 9.4 (standard deviation [SD] 11.4) and 8.8 (SD 13.0) mm Hg in relaxation response and control groups, respectively (both ps <0.0001) without group difference (p=0.75). DBP decreased 1.5 (SD 6.2) and 2.4 (SD 6.9) mm Hg (p=0.05 and 0.01, respectively) without group difference (p=0.48). Forty-four (44) in the relaxation response group and 36 in the control group were eligible for supervised antihypertensive medication elimination. After controlling for differences in characteristics at the start of medication elimination, patients in the relaxation response group were more likely to successfully eliminate an antihypertensive medication (odds ratio 4.3, 95% confidence interval 1.2-15.9, p=0.03). Although both groups had similar reductions in SBP, significantly more participants in the relaxation response group eliminated an antihypertensive medication while maintaining adequate blood pressure control.

Kefir drink leads to a similar weight loss, compared with milk, in a dairy-rich non-energy-restricted diet in overweight or obese premenopausal women: a randomized controlled trial.

PubMed

Fathi, Yasamin; Faghih, Shiva; Zibaeenezhad, Mohammad Javad; Tabatabaei, Sayed Hamid Reza

2016-02-01

Controversy exists regarding whether increasing dairy intake without energy restriction would lead to weight loss. We aimed to compare the potential weight-reducing effects of kefir drink (a probiotic dairy product) and milk in a dairy-rich non-energy-restricted diet in overweight or obese premenopausal women. One hundred and forty-four subjects were assessed for eligibility in this single-center, multi-arm, parallel-group, randomized controlled trial. Of these, seventy-five eligible women aged 25-45 years were randomly assigned to three groups, labeled as control, milk, and kefir, to receive an outpatient dietary regimen for 8 weeks. Subjects in the control group received a diet providing a maintenance level of energy intake, containing 2 servings/day of low-fat dairy products, while those in the milk and kefir groups received a weight maintenance diet, containing 2 additional servings/day (a total of 4 servings/day) of dairy products from low-fat milk or commercial kefir drink, respectively. Anthropometric outcomes including weight, body mass index (BMI), and waist circumference (WC) were measured every 2 weeks. Fifty-eight subjects completed the study. Using analysis of covariance models in the intention-to-treat population (n = 75), we found that at 8 weeks, subjects in the kefir and milk groups had significantly greater reductions in weight, BMI, and WC compared to those in the control group (all p < 0.01). However, no such significant differences were found between the kefir and milk groups. Kefir drink leads to a similar weight loss, compared with milk, in a dairy-rich non-energy-restricted diet in overweight or obese premenopausal women. However, further studies are warranted.

Mental practice for upper limb rehabilitation after stroke: a systematic review and meta-analysis.

PubMed

Park, Si-Woon; Kim, Jae-Hyung; Yang, Yun-Jung

2018-06-14

Mental practice (MP) is usually provided in combination with other therapies, and new developments for neurofeedback to support MP have been made recently. The objectives of this study were to evaluate the effectiveness of MP and to investigate the intervention characteristics including neurofeedback that may affect treatment outcome. The Cochrane Central Register of Controlled Trials, PubMed, Embase, KoreaMed, Scopus, Web of Science, PEDro, and CIRRIE were searched from inception to March 2017 for randomized controlled trials to assess the effect of MP for upper limb rehabilitation after stroke. Fugl-Meyer Assessment (FMA) was used as the outcome measure for meta-analysis. Twenty-five trials met the inclusion criteria, and 15 trials were eligible for meta-analysis. Among the trials selected for meta-analysis, MP was added to conventional therapy in eight trials or to modified constraint-induced movement therapy in one trial. The other trials provided neurofeedback to support MP: MP-guided neuromuscular electrical stimulation (NMES) in four trials and MP-guided robot-assisted therapy (RAT) in two trials. MP added to conventional therapy resulted in significantly higher FMA gain than conventional therapy alone. MP-guided NMES showed superior result than conventional NMES as well. However, the FMA gain of MP-guided RAT was not significantly higher than RAT alone. We suggest that MP is an effective complementary therapy either given with neurofeedback or not. Neurofeedback applied to MP showed different results depending on the therapy provided. This study has limitations because of heterogeneity and inadequate quality of trials. Further research is requested.

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.

Milnacipran versus other antidepressive agents for depression.

PubMed

Nakagawa, Atsuo; Watanabe, Norio; Omori, Ichiro M; Barbui, Corrado; Cipriani, Andrea; McGuire, Hugh; Churchill, Rachel; Furukawa, Toshi A

2009-07-08

Although pharmacological and psychological interventions are both effective for major depression, antidepressant drugs are frequently used as first-line treatment in primary and secondary care settings. Milnacipran, a dual serotonin-norepinephrine reuptake inhibitor (SNRI), is one of the antidepressant drugs that clinicians use for routine depression care. To assess the evidence for the efficacy, acceptability and tolerability of milnacipran in comparison with tricyclic antidepressants (TCAs), heterocyclics, SSRIs and other newer antidepressive agents in the acute-phase treatment of major depression. The Cochrane Collaboration Depression, Anxiety & Neurosis review group Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) were electronically searched in August 2008. References of relevant trials and other reviews were also checked. Trial databases of the drug-approving agencies and ongoing clinical trial registers for all published and unpublished trials were hand-searched in 2007. All relevant authors were contacted for supplemental data. No language restriction was applied. Randomised controlled trials comparing milnacipran with any other active antidepressive agents (including non-conventional agents such as herbal products like hypericum) as monotherapy in the acute phase of major depression were selected. Two reviewers independently checked eligibility, assessed methodological quality and extracted data from the eligible trials using a standardised data extraction form. The number of participants who responded to treatment or those who achieved remission were calculated on an intention-to-treat basis. Random-effects meta-analyses were conducted, combining data from the included trials. A total of 16 randomised controlled trials (n=2277) were included in the meta-analysis.Despite the size of this sample, the pooled 95% confidence intervals were rather wide and there were no statistically significant differences in efficacy, acceptability and tolerability when comparing milnacipran with other antidepressive agents. However, compared with TCAs, patients taking milnacipran were associated with fewer dropouts due to adverse events (OR 0.55; 95%CI 0.35 to 0.85). There was also some weak evidence to suggest that patients taking milnacipran experienced fewer adverse events of sleepiness/ drowsiness, dry mouth or constipation compared with TCAs. Currently, there is inadequate evidence to conclude whether milnacipran is superior, inferior or the same as other antidepressive agents in terms of efficacy, acceptability and tolerability in the acute phase treatment of major depression. However, there is some evidence in favour of milnacipran over TCAs in terms of dropouts due to adverse events (acceptability) and the rates of experiencing adverse events (tolerability). Information about other clinically meaningful outcomes such as cost-effectiveness and social functioning, including the ability to return to work, is lacking. Further study is needed to answer whether milnacipran would be the better choice of antidepressant for acute major depression.

Milnacipran versus other antidepressive agents for depression

PubMed Central

Nakagawa, Atsuo; Watanabe, Norio; Omori, Ichiro M; Barbui, Corrado; Cipriani, Andrea; McGuire, Hugh; Churchill, Rachel; Furukawa, Toshi A

2014-01-01

Background Although pharmacological and psychological interventions are both effective for major depression, antidepressant drugs are frequently used as first-line treatment in primary and secondary care settings. Milnacipran, a dual serotonin-norepinephrine reuptake inhibitor (SNRI), is one of the antidepressant drugs that clinicians use for routine depression care. Objectives To assess the evidence for the efficacy, acceptability and tolerability of milnacipran in comparison with tricyclic antidepressants (TCAs), heterocyclics, SSRIs and other newer antidepressive agents in the acute-phase treatment of major depression. Search methods The Cochrane Collaboration Depression, Anxiety & Neurosis review group Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) were electronically searched in August 2008. References of relevant trials and other reviews were also checked. Trial databases of the drug-approving agencies and ongoing clinical trial registers for all published and unpublished trials were handsearched in 2007. All relevant authors were contacted for supplemental data. No language restriction was applied. Selection criteria Randomised controlled trials comparing milnacipran with any other active antidepressive agents (including non-conventional agents such as herbal products like hypericum) as monotherapy in the acute phase of major depression were selected. Data collection and analysis Two reviewers independently checked eligibility, assessed methodological quality and extracted data from the eligible trials using a standardised data extraction form. The number of participants who responded to treatment or those who achieved remission were calculated on an intention-to-treat basis. Random-effects meta-analyses were conducted, combining data from the included trials. Main results A total of 16 randomised controlled trials (n=2277) were included in the meta-analysis. Despite the size of this sample, the pooled 95% confidence intervals were rather wide and there were no statistically significant differences in efficacy, acceptability and tolerability when comparing milnacipran with other antidepressive agents. However, compared with TCAs, patients taking milnacipran were associated with fewer dropouts due to adverse events (OR 0.55; 95%CI 0.35 to 0.85). There was also some weak evidence to suggest that patients taking milnacipran experienced fewer adverse events of sleepiness/drowsiness, dry mouth or constipation compared with TCAs. Authors’ conclusions Currently, there is inadequate evidence to conclude whether milnacipran is superior, inferior or the same as other antidepressive agents in terms of efficacy, acceptability and tolerability in the acute phase treatment of major depression. However, there is some evidence in favour of milnacipran over TCAs in terms of dropouts due to adverse events (acceptability) and the rates of experiencing adverse events (tolerability). Information about other clinically meaningful outcomes such as cost-effectiveness and social functioning, including the ability to return to work, is lacking. Further study is needed to answer whether milnacipran would be the better choice of antidepressant for acute major depression. PMID:19588396

The STRIPES trial--support to rural India's public education system.

PubMed

Eble, Alex; Mann, Vera; Bhakta, Preetha; Lakshminarayana, Rashmi; Frost, Chris; Elbourne, Diana; Boone, Peter

2010-02-01

Performance of primary school students in India lags far below government expectations, and major disparity exists between rural and urban areas. The Naandi Foundation has designed and implemented a programme using community members to deliver after-school academic support for children in over 1,100 schools in five Indian states. Assessments to date suggest that it might have a substantial effect. This trial aims to evaluate the impact of this programme in villages of rural Andhra Pradesh and will compare test scores for children in three arms: a control and two intervention arms. In both intervention arms additional after-school instruction and learning materials will be offered to all eligible children and in one arm girls will also receive an additional 'kit' with a uniform and clothes. The trial is a cluster-randomised controlled trial conducted in conjunction with the CHAMPION trial. In the CHAMPION trial 464 villages were randomised so that half receive health interventions aiming to reduce neonatal mortality. STRIPES will be introduced in those CHAMPION villages which have a public primary school attended by at least 15 students at the time of a baseline test in 2008. 214 villages of the 464 were found to fulfil above criteria, 107 belonging to the control and 107 to the intervention arm of the CHAMPION trial. These latter 107 villages will serve as control villages in the STRIPES trial. A further randomisation will be carried out within the 107 STRIPES intervention villages allocating half to receive an additional kit for girls on the top of the instruction and learning materials. The primary outcome of the trial is a composite maths and language test score. The study is designed to measure (i) whether the educational intervention affects the exam score of children compared to the control arm, (ii) if the exam scores of girls who receive the additional kit are different from those of girls living in the other STRIPES intervention arm. One of the goals of the STRIPES trial is to provide benefit to the controls of the CHAMPION trial. We will also conduct a cost-benefit analysis in which we calculate the programme cost for 0.1 standard deviation improvement for both intervention arms. Current controlled trials ISRCTN69951502.

Eligibility of Metastatic Pancreatic Cancer Patients for First-Line Palliative Intent nab-Paclitaxel Plus Gemcitabine Versus FOLFIRINOX.

PubMed

Peixoto, Renata D; Ho, Maria; Renouf, Daniel J; Lim, Howard J; Gill, Sharlene; Ruan, Jenny Y; Cheung, Winson Y

2017-10-01

The PRODIGE and MPACT trials showed superiority of FOLFIRINOX and nab-paclitaxel plus gemcitabine (NG) over gemcitabine alone, respectively. However, both had strict inclusion criteria. We sought to determine the characteristics of patients with metastatic pancreatic cancer (MPC) which inform the appropriateness of first-line chemotherapy FOLFIRINOX and NG in routine practice. Patients with MPC who initiated palliative chemotherapy with gemcitabine from 2000 to 2011 at the British Columbia Cancer Agency were identified. Clinicopathologic variables and outcomes were retrospectively collected and compared among groups. Eligibility criteria for each regimen were in accordance with the respective pivotal phase III trials. A total of 473 patients were included: 25% of the patients were eligible for FOLFIRINOX versus 45% for NG. Main reasons for FOLFIRINOX ineligibility were Eastern Cooperative Oncology Group (ECOG) performance status (PS)≥2 (56.5%), age older than 75 years (19.0%), and bilirubin>1.5× upper limit of normal (18.6%), whereas those for NG ineligibility were bilirubin > upper limit of normal (24.5%), ECOG PS≥3 (14.6%), and cardiac dysfunction (13.8%). Univariate analyses revealed that FOLFIRINOX and NG-eligible patients had longer median overall survival than their respective ineligible group (8.6 vs. 4.7 mo, P<0.001; 6.7 vs. 4.9 mo, P=0.008, respectively). After accounting for ECOG PS in the multivariate model, however, eligibility for either FOLFIRINOX or NG no longer predicted for better overall survival. The majority of patients with MPC are not candidates to either NG or FOLFIRINOX due to restrictive eligibility requirements. Specific trials addressing the unmet needs of protocol ineligible patients are warranted.

Visual Aggregate Analysis of Eligibility Features of Clinical Trials

PubMed Central

He, Zhe; Carini, Simona; Sim, Ida; Weng, Chunhua

2015-01-01

Objective To develop a method for profiling the collective populations targeted for recruitment by multiple clinical studies addressing the same medical condition using one eligibility feature each time. Methods Using a previously published database COMPACT as the backend, we designed a scalable method for visual aggregate analysis of clinical trial eligibility features. This method consists of four modules for eligibility feature frequency analysis, query builder, distribution analysis, and visualization, respectively. This method is capable of analyzing (1) frequently used qualitative and quantitative features for recruiting subjects for a selected medical condition, (2) distribution of study enrollment on consecutive value points or value intervals of each quantitative feature, and (3) distribution of studies on the boundary values, permissible value ranges, and value range widths of each feature. All analysis results were visualized using Google Charts API. Five recruited potential users assessed the usefulness of this method for identifying common patterns in any selected eligibility feature for clinical trial participant selection. Results We implemented this method as a Web-based analytical system called VITTA (Visual Analysis Tool of Clinical Study Target Populations). We illustrated the functionality of VITTA using two sample queries involving quantitative features BMI and HbA1c for conditions “hypertension” and “Type 2 diabetes”, respectively. The recruited potential users rated the user-perceived usefulness of VITTA with an average score of 86.4/100. Conclusions We contributed a novel aggregate analysis method to enable the interrogation of common patterns in quantitative eligibility criteria and the collective target populations of multiple related clinical studies. A larger-scale study is warranted to formally assess the usefulness of VITTA among clinical investigators and sponsors in various therapeutic areas. PMID:25615940

Visual aggregate analysis of eligibility features of clinical trials.

PubMed

He, Zhe; Carini, Simona; Sim, Ida; Weng, Chunhua

2015-04-01

To develop a method for profiling the collective populations targeted for recruitment by multiple clinical studies addressing the same medical condition using one eligibility feature each time. Using a previously published database COMPACT as the backend, we designed a scalable method for visual aggregate analysis of clinical trial eligibility features. This method consists of four modules for eligibility feature frequency analysis, query builder, distribution analysis, and visualization, respectively. This method is capable of analyzing (1) frequently used qualitative and quantitative features for recruiting subjects for a selected medical condition, (2) distribution of study enrollment on consecutive value points or value intervals of each quantitative feature, and (3) distribution of studies on the boundary values, permissible value ranges, and value range widths of each feature. All analysis results were visualized using Google Charts API. Five recruited potential users assessed the usefulness of this method for identifying common patterns in any selected eligibility feature for clinical trial participant selection. We implemented this method as a Web-based analytical system called VITTA (Visual Analysis Tool of Clinical Study Target Populations). We illustrated the functionality of VITTA using two sample queries involving quantitative features BMI and HbA1c for conditions "hypertension" and "Type 2 diabetes", respectively. The recruited potential users rated the user-perceived usefulness of VITTA with an average score of 86.4/100. We contributed a novel aggregate analysis method to enable the interrogation of common patterns in quantitative eligibility criteria and the collective target populations of multiple related clinical studies. A larger-scale study is warranted to formally assess the usefulness of VITTA among clinical investigators and sponsors in various therapeutic areas. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

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

Evaluating the addition of oxaliplatin to single agent fluoropyrimidine in the treatment of locally advanced rectal cancer: a systematic review and meta-analysis.

PubMed

Thavaneswaran, Subotheni; Kok, Peey Sei; Price, Timothy

2017-10-01

Multimodality treatment of patients with locally advanced rectal cancer (LARC) has significantly improved local disease control, however the unaltered overall survival (OS) implicates an inability to further control micrometastases, providing rationale for intensified systemic treatment. A systematic review was conducted to evaluate the efficacy and toxicity of adding oxaliplatin to a fluoropyrimidine (intervention) compared with fluoropyrimidine alone (control) in the treatment of LARC. We searched CENTRAL, Medline Ovid, PubMed and EMBASE databases. Randomised trials comparing the intervention and control delivered either pre- or post-operatively were included. Seven trials involving 4444 patients were identified; five studies evaluated the intervention vs control preoperatively; one study peri-operatively; and one, post-operatively. There was no significant difference in OS with oxaliplatin addition, HR 0.89, 95% CI, 0.75 to 1.06. There was however an improvement in disease free survival, 3-year local and distant recurrence rates (RR) favouring oxaliplatin. Preoperative oxaliplatin improved pathological complete response (pCR), but with a greater toxicity and reduced compliance with radiation. There is no OS benefit with oxaliplatin, despite improved pCR, local and distant RR. Before drawing definitive conclusions, longer follow-up in included trials and availability of published data from other eligible studies, including the induction setting, are needed.

Reporting of clinical trials: a review of research funders' guidelines

PubMed Central

Dwan, Kerry; Gamble, Carrol; Williamson, Paula R; Altman, Douglas G

2008-01-01

Background Randomised controlled trials (RCTs) represent the gold standard methodological design to evaluate the effectiveness of an intervention in humans but they are subject to bias, including study publication bias and outcome reporting bias. National and international organisations and charities give recommendations for good research practice in relation to RCTs but to date no review of these guidelines has been undertaken with respect to reporting bias. Methods National and international organisations and UK based charities listed on the Association for Medical Research Charities website were contacted in 2007; they were considered eligible for this review if they funded RCTs. Guidelines were obtained and assessed in relation to what was written about trial registration, protocol adherence and trial publication. It was also noted whether any monitoring against these guidelines was undertaken. This information was necessary to discover how much guidance researchers are given on the publication of results, in order to prevent study publication bias and outcome reporting bias. Results Seventeen organisations and 56 charities were eligible of 140 surveyed for this review, although there was no response from 12. Trial registration, protocol adherence, trial publication and monitoring against the guidelines were often explicitly discussed or implicitly referred too. However, only eleven of these organisations or charities mentioned the publication of negative as well as positive outcomes and just three of the organisations specifically stated that the statistical analysis plan should be strictly adhered to and all changes should be reported. Conclusion Our review indicates that there is a need to provide more detailed guidance for those conducting and reporting clinical trials to help prevent the selective reporting of results. Statements found in the guidelines generally refer to publication bias rather than outcome reporting bias. Current guidelines need to be updated and include the statement that all primary and secondary outcomes prespecified in the protocol should be fully reported and should not be selected for inclusion in the final report based on their results. PMID:19032743

Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis.

PubMed

Schuetz, Philipp; Wirz, Yannick; Sager, Ramon; Christ-Crain, Mirjam; Stolz, Daiana; Tamm, Michael; Bouadma, Lila; Luyt, Charles E; Wolff, Michel; Chastre, Jean; Tubach, Florence; Kristoffersen, Kristina B; Burkhardt, Olaf; Welte, Tobias; Schroeder, Stefan; Nobre, Vandack; Wei, Long; Bucher, Heiner C; Annane, Djillali; Reinhart, Konrad; Falsey, Ann R; Branche, Angela; Damas, Pierre; Nijsten, Maarten; de Lange, Dylan W; Deliberato, Rodrigo O; Oliveira, Carolina F; Maravić-Stojković, Vera; Verduri, Alessia; Beghé, Bianca; Cao, Bin; Shehabi, Yahya; Jensen, Jens-Ulrik S; Corti, Caspar; van Oers, Jos A H; Beishuizen, Albertus; Girbes, Armand R J; de Jong, Evelien; Briel, Matthias; Mueller, Beat

2018-01-01

In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings. Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control. The coprimary endpoints were 30-day mortality and setting-specific treatment failure. Secondary endpoints were antibiotic use, length of stay, and antibiotic side-effects. We identified 990 records from the literature search, of which 71 articles were assessed for eligibility after exclusion of 919 records. We collected data on 6708 patients from 26 eligible trials in 12 countries. Mortality at 30 days was significantly lower in procalcitonin-guided patients than in control patients (286 [9%] deaths in 3336 procalcitonin-guided patients vs 336 [10%] in 3372 controls; adjusted odds ratio [OR] 0·83 [95% CI 0·70 to 0·99], p=0·037). This mortality benefit was similar across subgroups by setting and type of infection (p interactions >0·05), although mortality was very low in primary care and in patients with acute bronchitis. Procalcitonin guidance was also associated with a 2·4-day reduction in antibiotic exposure (5·7 vs 8·1 days [95% CI -2·71 to -2·15], p<0·0001) and a reduction in antibiotic-related side-effects (16% vs 22%, adjusted OR 0·68 [95% CI 0·57 to 0·82], p<0·0001). Use of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance. National Institute for Health Research. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Radical Extent of lymphadenectomy - D2 dissection versus complete mesocolic excision of LAparoscopic Right Colectomy for right-sided colon cancer (RELARC) trial: study protocol for a randomized controlled trial.

PubMed

Lu, Jun-Yang; Xu, Lai; Xue, Hua-Dan; Zhou, Wei-Xun; Xu, Tao; Qiu, Hui-Zhong; Wu, Bin; Lin, Guo-Le; Xiao, Yi

2016-12-08

The extent of lymphadenectomy during laparoscopic right colectomy can affect the oncological outcome and the safety of surgery. The principle of complete mesocolic excision (CME) has been gradually accepted and increasingly applied by colorectal surgeons. The aim of this study is to investigate whether extended lymphadenectomy (CME) in laparoscopic colectomy could improve the oncological outcomes of patients with right-sided colon cancers, compared with D2 lymphadenectomy. The Radical Extent of lympadenectomy: D2 dissection versus complete mesocolic excision of LAparoscopic Right Colectomy for right-sided colon cancer (RELARC) study is a prospective, multicenter, randomized controlled trial in which 1072 eligible patients with right-sided colon cancers will be randomly assigned to the CME group or the D2 dissection group during laparoscopic right colectomy. Inclusion criteria are locally advanced colon cancers situated from the cecum to the right third of the transverse colon and clinically staged as T2-4aN0M0 or TanyN + M0. The primary endpoint of this trial is 3-year disease-free survival. Secondary endpoints include 3-year overall survival, postoperative complication rates, perioperative mortality rates, and rates of positive central lymph nodes (the station 3 nodes). The RELARC trial is a prospective, multicenter, randomized controlled trial that will provide evidence on the optimal extent of lymphadenectomy during laparoscopic right colectomy in terms of better oncological outcome and operation safety. ClinicalTrials.gov: NCT02619942 . Registered on 29 November 2015.

DeLLITE depression in late life: an intervention trial of exercise. Design and recruitment of a randomised controlled trial.

PubMed

Kerse, Ngaire; Falloon, Karen; Moyes, Simon A; Hayman, Karen J; Dowell, Tony; Kolt, Gregory S; Elley, C Raina; Hatcher, Simon; Peri, Kathy; Keeling, Sally; Robinson, Elizabeth; Parsons, John; Wiles, Janine; Arroll, Bruce

2008-05-24

Physical activity shows potential in combating the poor outcomes associated with depression in older people. Meta-analyses show gaps in the research with poor trial design compromising certainty in conclusions and few programmes showing sustained effects. The Depression in Late Life: an Intervention Trial of Exercise (DeLLITE) is a 12 month randomised controlled trial of a physical activity intervention to increase functional status in people aged 75 years and older with depressive symptoms. The intervention involves an individualised activity programme based on goal setting and progression of difficulty of activities delivered by a trained nurse during 8 home visits over 6 months. The control group received time matched home visits to discuss social contacts and networks. Baseline, 6 and 12 months measures were assessed in face to face visits with the primary outcome being functional status (SPPB, NEADL). Secondary outcomes include depressive symptoms (Geriatric Depression Scale), quality of life (SF-36), physical activity (AHS Physical Activity Questionnaire) and falls (self report). Due to report in 2008 the DeLLITE study has recruited 70% of those eligible and tests the efficacy of a home based, goal setting physical activity programme in improving function, mood and quality of life in older people with depressive symptomatology. If successful in improving function and mood this trial could prove for the first time that there are long term health benefit of physical activity, independent of social activity, in this high risk group who consume excess health related costs. Australian and New Zealand Clinical Trials Register ACTRN12605000475640.

Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock.

PubMed

Lamontagne, François; Day, Andrew G; Meade, Maureen O; Cook, Deborah J; Guyatt, Gordon H; Hylands, Mathieu; Radermacher, Peter; Chrétien, Jean-Marie; Beaudoin, Nicolas; Hébert, Paul; D'Aragon, Frédérick; Meziani, Ferhat; Asfar, Pierre

2018-01-01

Guidelines for shock recommend mean arterial pressure (MAP) targets for vasopressor therapy of at least 65 mmHg and, until recently, suggested that patients with underlying chronic hypertension and atherosclerosis may benefit from higher targets. We conducted an individual patient-data meta-analysis of recent trials to determine if patient variables modify the effect of different MAP targets. We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials of higher versus lower blood pressure targets for vasopressor therapy in adult patients in shock (until November 2017). After obtaining individual patient data from both eligible trials, we used a modified version of the Cochrane Collaboration's instrument to assess the risk of bias of included trials. The primary outcome was 28-day mortality. Included trials enrolled 894 patients. Controlling for trial and site, the OR for 28-day mortality for the higher versus lower MAP targets was 1.15 (95% CI 0.87-1.52). Treatment effect varied by duration of vasopressors before randomization (interaction p = 0.017), but not by chronic hypertension, congestive heart failure or age. Risk of death increased in higher MAP groups among patients on vasopressors > 6 h before randomization (OR 3.00, 95% CI 1.33-6.74). Targeting higher blood pressure targets may increase mortality in patients who have been treated with vasopressors for more than 6 h. Lower blood pressure targets were not associated with patient-important adverse events in any subgroup, including chronically hypertensive patients.

Meta-analysis of letrozole versus clomiphene citrate in polycystic ovary syndrome.

PubMed

He, Donghong; Jiang, Fengyan

2011-07-01

The aim of this study was to systematically compare the clinical efficacy and safety of letrozole with clomiphene citrate for ovulation induction in women with polycystic ovary syndrome (PCOS). The Cochrane Central Register of Controlled Trials, PubMed, EMbase, CBMdisc and CNKI were searched for eligible randomized controlled trials (RCT) comparing letrozole with clomiphene citrate in PCOS patients. Two reviewers independently extracted information and evaluated methodological quality according to the Cochrane Handbook 5.0. Meta-analysis was performed with the fixed-effects model or random-effects model according to the heterogeneity. Six eligible RCT involving 841 patients were included. Letrozole was associated with a number of lower mature follicles per cycle (standardized mean difference (SMD) -1.41; 95% confidence intervales (CI) -1.54 to -1.28; P<0.00001) compared with clomiphene citrate. There were no significant differences in pregnancy rate (relative risk (RR) 0.97; 95% CI 0.79 to 1.18), abortion rate (RR 1.38; 95% CI 0.48 to -3.96) and multiple pregnancy rate (RR 0.34; 95% CI 0.07 to -1.72) between the two groups. The evidence from ovulation rates was not enough to support either letrozole or clomiphene citrate. In conclusion, letrozole is as effective as clomiphene citrate for ovulation induction in patients with PCOS. Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

The intellectual challenges and emotional consequences of equipoise contributed to the fragility of recruitment in six randomized controlled trials.

PubMed

Donovan, Jenny L; de Salis, Isabel; Toerien, Merran; Paramasivan, Sangeetha; Hamdy, Freddie C; Blazeby, Jane M

2014-08-01

The aim of the study was to investigate how doctors considered and experienced the concept of equipoise while recruiting patients to randomized controlled trials (RCTs). In-depth interviews with 32 doctors in six publicly funded pragmatic RCTs explored their perceptions of equipoise as they undertook RCT recruitment. The RCTs varied in size, duration, type of complex intervention, and clinical specialties. Interview data were analyzed using qualitative content and thematic analytical methods derived from grounded theory and synthesized across six RCTs. All six RCTs suffered from poor recruitment. Doctors wanted to gather robust evidence but experienced considerable discomfort and emotion in relation to their clinical instincts and concerns about patient eligibility and safety. Although they relied on a sense of community equipoise to justify participation, most acknowledged having "hunches" about particular treatments and patients, some of which undermined recruitment. Surgeons experienced these issues most intensely. Training and support promoted greater confidence in equipoise and improved engagement and recruitment. Recruitment to RCTs is a fragile process and difficult for doctors intellectually and emotionally. Training and support can enable most doctors to become comfortable with key RCT concepts including equipoise, uncertainty, patient eligibility, and randomization, promoting a more resilient recruitment process in partnership with patients. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Effectiveness of horticultural therapy: a systematic review of randomized controlled trials.

PubMed

Kamioka, Hiroharu; Tsutani, Kiichiro; Yamada, Minoru; Park, Hyuntae; Okuizumi, Hiroyasu; Honda, Takuya; Okada, Shinpei; Park, Sang-Jun; Kitayuguchi, Jun; Abe, Takafumi; Handa, Shuichi; Mutoh, Yoshiteru

2014-10-01

To summarize the evidence from randomized controlled trials (RCTs) on the effects of horticultural therapy (HT). Studies were eligible if they were RCTs. Studies included one treatment group in which HT was applied. We searched the following databases from 1990 up to August 20, 2013: MEDLINE via PubMed, CINAHL, Web of Science, Ichushi-Web, GHL, WPRIM, and PsyclNFO. We also searched all Cochrane Database and Campbell Systematic Reviews up to September 20, 2013. Four studies met all inclusion criteria. The language of all eligible publications was English and Korean. Target diseases and/or symptoms were dementia, severe mental illness such as schizophrenia, bipolar disorder, and major depression, frail elderly in nursing home, and hemiplegic patients after stroke. These studies showed significant effectiveness in one or more outcomes for mental health and behavior. However, our review especially detected omissions of the following descriptions: method used to generate randomization, concealment, blinding, and intention-to-treat analysis. In addition, the results of this study suggested that the RCTs conducted have been of relatively low quality. Although there was insufficient evidence in the studies of HT due to poor methodological and reporting quality and heterogeneity, HT may be an effective treatment for mental and behavioral disorders such as dementia, schizophrenia, depression, and terminal-care for cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Disease activity indices in coeliac disease: systematic review and recommendations for clinical trials.

PubMed

Hindryckx, Pieter; Levesque, Barrett G; Holvoet, Tom; Durand, Serina; Tang, Ceen-Ming; Parker, Claire; Khanna, Reena; Shackelton, Lisa M; D'Haens, Geert; Sandborn, William J; Feagan, Brian G; Lebwohl, Benjamin; Leffler, Daniel A; Jairath, Vipul

2018-01-01

Although several pharmacological agents have emerged as potential adjunctive therapies to a gluten-free diet for coeliac disease, there is currently no widely accepted measure of disease activity used in clinical trials. We conducted a systematic review of coeliac disease activity indices to evaluate their operating properties and potential as outcome measures in registration trials. MEDLINE, EMBASE and the Cochrane central library were searched from 1966 to 2015 for eligible studies in adult and/or paediatric patients with coeliac disease that included coeliac disease activity markers in their outcome measures. The operating characteristics of histological indices, patient-reported outcomes (PROs) and endoscopic indices were evaluated for content and construct validity, reliability, responsiveness and feasibility using guidelines proposed by the US Food and Drug Administration (FDA). Of 19 123 citations, 286 studies were eligible, including 24 randomised-controlled trials. Three of five PROs identified met most key evaluative criteria but only the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) have been approved by the FDA. All histological and endoscopic scores identified lacked content validity. Quantitative morphometric histological analysis had better reliability and responsiveness compared with qualitative scales. Endoscopic indices were infrequently used, and only one index demonstrated responsiveness to effective therapy. Current best evidence suggests that the CDSD and the CeD PRO are appropriate for use in the definition of primary end points in coeliac disease registration trials. Morphometric histology should be included as a key secondary or co-primary end point. Further work is needed to optimise end point configuration to inform efficient drug development. 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/.

The effect of cactus pear (Opuntia ficus-indica) on body weight and cardiovascular risk factors: a systematic review and meta-analysis of randomized clinical trials.

PubMed

Onakpoya, Igho J; O'Sullivan, Jack; Heneghan, Carl J

2015-05-01

Hundreds of dietary supplements are currently marketed as weight loss supplements. However, the advertised health claims of effectiveness for most of these have not been proven. The aim of this study was to critically appraise and evaluate the evidence for effectiveness of cactus pear, Opuntia ficus-indica (OFI), using data from published randomized clinical trials. We conducted electronic searches in Medline, Embase, Amed, Cinahl, and the Cochrane Library. No restrictions on age, time, or language were imposed. The risk for bias in the studies included was assessed using the Cochrane Collaboration criteria. Two reviewers independently determined the eligibility of included studies, assessed reporting quality, and extracted data. We identified seven eligible studies, of which five were included. The studies varied in design and reporting quality. Meta-analysis revealed a nonsignificant difference in body weight between OFI and controls (mean difference = -0.83 kg; 95% confidence interval, -2.49 to 0.83; I(2) = 93%). Significant reductions in body mass index, percentage body fat, systolic and diastolic blood pressures, and total cholesterol were observed. Adverse events included gastric intolerance and flu symptoms. The evidence from randomized clinical trials does not indicate that supplementation with OFI generates statistically significant effects on body weight. Consumption of OFI can cause significant reductions in percentage body fat, blood pressure, and total cholesterol. Few clinical trials evaluating the effects of OFI have been published. They vary in design and methodology, and are characterized by inconsistent quality of reporting. Further clinical trials evaluating the effects of OFI on body composition and metabolic parameters are warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

Valuing breastfeeding: a qualitative study of women's experiences of a financial incentive scheme for breastfeeding.

PubMed

Johnson, Maxine; Whelan, Barbara; Relton, Clare; Thomas, Kate; Strong, Mark; Scott, Elaine; Renfrew, Mary J

2018-01-08

A cluster randomised controlled trial of a financial incentive for breastfeeding conducted in areas with low breastfeeding rates in the UK reported a statistically significant increase in breastfeeding at 6-8 weeks. In this paper we report an analysis of interviews with women eligible for the scheme, exploring their experiences and perceptions of the scheme and its impact on breastfeeding to support the interpretation of the results of the trial. Semi-structured interviews were carried out with 35 women eligible for the scheme during the feasibility and trial stages. All interviews were recorded and verbatim transcripts analysed using a Framework Analysis approach. Women reported that their decisions about infant feeding were influenced by the behaviours and beliefs of their family and friends, socio-cultural norms and by health and practical considerations. They were generally positive about the scheme, and felt valued for the effort involved in breastfeeding. The vouchers were frequently described as a reward, a bonus and something to look forward to, and helping women keep going with their breastfeeding. They were often perceived as compensation for the difficulties women encountered during breastfeeding. The scheme was not thought to make a difference to mothers who were strongly against breastfeeding. However, women did believe the scheme would help normalise breastfeeding, influence those who were undecided and help women to keep going with breastfeeding and reach key milestones e.g. 6 weeks or 3 months. The scheme was acceptable to women, who perceived it as rewarding and valuing them for breastfeeding. Women reported that the scheme could raise awareness of breastfeeding and encourage its normalisation. This provides a possible mechanism of action to explain the results of the trial. The trial is registered with the ISRCTN registry, number 44898617 , https://www.isrctn.com.

Effectiveness of policy to provide breastfeeding groups (BIG) for pregnant and breastfeeding mothers in primary care: cluster randomised controlled trial

PubMed Central

Britten, Jane; Prescott, Gordon J; Tappin, David; Ludbrook, Anne; Godden, David J

2009-01-01

Objective To assess the clinical effectiveness and cost effectiveness of a policy to provide breastfeeding groups for pregnant and breastfeeding women. Design Cluster randomised controlled trial with prospective mixed method embedded case studies to evaluate implementation processes. Setting Primary care in Scotland. Participants Pregnant women, breastfeeding mothers, and babies registered with 14 of 66 eligible clusters of general practices (localities) in Scotland that routinely collect breastfeeding outcome data. Intervention Localities set up new breastfeeding groups to provide population coverage; control localities did not change group activity. Main outcome measures Primary outcome: any breast feeding at 6-8 weeks from routinely collected data for two pre-trial years and two trial years. Secondary outcomes: any breast feeding at birth, 5-7 days, and 8-9 months; maternal satisfaction. Results Between 1 February 2005 and 31 January 2007, 9747 birth records existed for intervention localities and 9111 for control localities. The number of breastfeeding groups increased from 10 to 27 in intervention localities, where 1310 women attended, and remained at 10 groups in control localities. No significant differences in breastfeeding outcomes were found. Any breast feeding at 6-8 weeks declined from 27% to 26% in intervention localities and increased from 29% to 30% in control localities (P=0.08, adjusted for pre-trial rate). Any breast feeding at 6-8 weeks increased from 38% to 39% in localities not participating in the trial. Women who attended breastfeeding groups were older (P<0.001) than women initiating breast feeding who did not attend and had higher income (P=0.02) than women in the control localities who attended postnatal groups. The locality cost was £13 400 (€14 410; $20 144) a year. Conclusion A policy for providing breastfeeding groups in relatively deprived areas of Scotland did not improve breastfeeding rates at 6-8 weeks. The costs of running groups would be similar to the costs of visiting women at home. Trial registration Current Controlled Trials ISRCTN44857041. PMID:19181729

Efficacy of infant simulator programmes to prevent teenage pregnancy: a school-based cluster randomised controlled trial in Western Australia.

PubMed

Brinkman, Sally A; Johnson, Sarah E; Codde, James P; Hart, Michael B; Straton, Judith A; Mittinty, Murthy N; Silburn, Sven R

2016-11-05

Infant simulator-based programmes, which aim to prevent teenage pregnancy, are used in high-income as well as low-income and middle-income countries but, despite growing popularity, no published evidence exists of their long-term effect. The aim of this trial was to investigate the effect of such a programme, the Virtual Infant Parenting (VIP) programme, on pregnancy outcomes of birth and induced abortion in Australia. In this school-based pragmatic cluster randomised controlled trial, eligible schools in Perth, Western Australia, were enrolled and randomised 1:1 to the intervention and control groups. Randomisation using a table of random numbers without blocking, stratification, or matching was done by a researcher who was masked to the identity of the schools. Between 2003 and 2006, the VIP programme was administered to girls aged 13-15 years in the intervention schools, while girls of the same age in the control schools received the standard health education curriculum. Participants were followed until they reached 20 years of age via data linkage to hospital medical and abortion clinic records. The primary endpoint was the occurrence of pregnancy during the teenage years. Binomial and Cox proportional hazards regression was used to test for differences in pregnancy rates between study groups. This study is registered as an international randomised controlled trial, number ISRCTN24952438. 57 (86%) of 66 eligible schools were enrolled into the trial and randomly assigned 1:1 to the intervention (28 schools) or the control group (29 schools). Then, between Feb 1, 2003, and May 31, 2006, 1267 girls in the intervention schools received the VIP programme while 1567 girls in the control schools received the standard health education curriculum. Compared with girls in the control group, a higher proportion of girls in the intervention group recorded at least one birth (97 [8%] of 1267 in the intervention group vs 67 [4%] of 1567 in the control group) or at least one abortion as the first pregnancy event (113 [9%] vs 101 [6%]). After adjustment for potential confounders, the intervention group had a higher overall pregnancy risk than the control group (relative risk 1·36 [95% CI 1·10-1·67], p=0·003). Similar results were obtained with the use of proportional hazard models (hazard ratio 1·35 [95% CI 1·10-1·67], p=0·016). The infant simulator-based VIP programme did not achieve its aim of reducing teenage pregnancy. Girls in the intervention group were more likely to experience a birth or an induced abortion than those in the control group before they reached 20 years of age. Western Australian Health Promotion Foundation (Healthway), Lotteries WA, the Western Australian Department of Education and Training, and the Western Australian Department of Health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identifying patients for clinical trials using fuzzy ternary logic expressions on HL7 messages.

PubMed

Majeed, Raphael W; Röhrig, Rainer

2011-01-01

Identifying eligible patients is one of the most critical parts of any clinical trial. The process of recruiting patients for the third phase of any clinical trial is usually done manually, informing relevant physicians or putting notes on bulletin boards. While most necessary information is already available in electronic hospital information systems, required data still has to be looked up individually. Most university hospitals make use of a dedicated communication server to distribute information from independent information systems, e.g. laboratory information systems, electronic health records, surgery planning systems. Thus, a theoretical model is developed to formally describe inclusion and exclusion criteria for each clinical trial using a fuzzy ternary logic expression. These expressions will then be used to process HL7 messages from a communication server in order to identify eligible patients.

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.

Evaluating a health care provider delivered intervention to reduce intimate partner violence and mitigate associated health risks: study protocol for a randomized controlled trial in Mexico City.

PubMed

Falb, Kathryn L; Diaz-Olavarrieta, Claudia; Campos, Paola A; Valades, Jimena; Cardenas, Roosebelinda; Carino, Giselle; Gupta, Jhumka

2014-07-30

Intimate partner violence (IPV) victimization is a prevalent issue among women residing in Mexico City. Comprehensive and integrated health care provider (HCP) delivered programs in clinic-settings are needed, yet few have been evaluated in Latin America, including Mexico. In addition, there has been minimal attention to interventions among lower income women presenting at settings outside of antenatal care clinics. The current randomized controlled trial seeks to increase midlevel HCPs' capacity, specifically nurses, who are often the first point of contact in this setting, to identify women presenting at health clinics with experiences of IPV and to assist these women with health risk mitigation. Specific outcomes include changes in past-year IPV (physical and/or sexual), reproductive coercion, safety planning, use of community resources, and quality of life. Forty-two public health clinics in Mexico City were randomized to treatment or control clinics. Nurses meeting eligibility criteria in treatment groups received an intensive training on screening for IPV, providing supportive referrals, and assessing for health and safety risks. Nurses meeting eligibility criteria at control clinics received the standard of care which included a one-day training focused on sensitizing staff to IPV as a health issue and referral cards to give to women. Women were screened for eligibility (currently experiencing abuse in a heterosexual relationship, 18-44 years of age, non-pregnant or in first trimester) by research assistants in private areas of waiting rooms in health clinics. Consenting women completed a baseline survey and received the study protocol for that clinic. In treatment clinics, women received the nurse delivered session at baseline and received a follow-up counseling session after three months. Surveys are conducted at baseline, three months, and fifteen months from baseline. This study will provide important insight into whether a nurse-delivered program can assist women currently experiencing abuse in a Latin American context. Findings can be used to inform IPV programs and policies in Mexico City's public health clinics. NCT01661504.

Preconception lifestyle advice for people with subfertility.

PubMed

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

2010-04-14

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

Interventions for supporting pregnant women's decision-making about mode of birth after a caesarean.

PubMed

Horey, Dell; Kealy, Michelle; Davey, Mary-Ann; Small, Rhonda; Crowther, Caroline A

2013-07-30

Pregnant women who have previously had a caesarean birth and who have no contraindication for vaginal birth after caesarean (VBAC) may need to decide whether to choose between a repeat caesarean birth or to commence labour with the intention of achieving a VBAC. Women need information about their options and interventions designed to support decision-making may be helpful. Decision support interventions can be implemented independently, or shared with health professionals during clinical encounters or used in mediated social encounters with others, such as telephone decision coaching services. Decision support interventions can include decision aids, one-on-one counselling, group information or support sessions and decision protocols or algorithms. This review considers any decision support intervention for pregnant women making birth choices after a previous caesarean birth. To examine the effectiveness of interventions to support decision-making about vaginal birth after a caesarean birth.Secondary objectives are to identify issues related to the acceptability of any interventions to parents and the feasibility of their implementation. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2013), Current Controlled Trials (22 July 2013), the WHO International Clinical Trials Registry Platform Search Portal (ICTRP) (22 July 2013) and reference lists of retrieved articles. We also conducted citation searches of included studies to identify possible concurrent qualitative studies. All published, unpublished, and ongoing randomised controlled trials (RCTs) and quasi-randomised trials with reported data of any intervention designed to support pregnant women who have previously had a caesarean birth make decisions about their options for birth. Studies using a cluster-randomised design were eligible for inclusion but none were identified. Studies using a cross-over design were not eligible for inclusion. Studies published in abstract form only would have been eligible for inclusion if data were able to be extracted. Two review authors independently applied the selection criteria and carried out data extraction and quality assessment of studies. Data were checked for accuracy. We contacted authors of included trials for additional information. All included interventions were classified as independent, shared or mediated decision supports. Consensus was obtained for classifications. Verification of the final list of included studies was undertaken by three review authors. Three randomised controlled trials involving 2270 women from high-income countries were eligible for inclusion in the review. Outcomes were reported for 1280 infants in one study. The interventions assessed in the trials were designed to be used either independently by women or mediated through the involvement of independent support. No studies looked at shared decision supports, that is, interventions designed to facilitate shared decision-making with health professionals during clinical encounters.We found no difference in planned mode of birth: VBAC (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.97 to 1.10; I² = 0%) or caesarean birth (RR 0.96, 95% CI 0.84 to 1.10; I² = 0%). The proportion of women unsure about preference did not change (RR 0.87, 95% CI 0.62 to 1.20; I² = 0%).There was no difference in adverse outcomes reported between intervention and control groups (one trial, 1275 women/1280 babies): permanent (RR 0.66, 95% CI 0.32 to 1.36); severe (RR 1.02, 95% CI 0.77 to 1.36); unclear (0.66, 95% CI 0.27, 1.61). Overall, 64.8% of those indicating preference for VBAC achieved it, while 97.1% of those planning caesarean birth achieved this mode of birth. We found no difference in the proportion of women achieving congruence between preferred and actual mode of birth (RR 1.02, 95% CI 0.96 to 1.07) (three trials, 1921 women).More women had caesarean births (57.3%), including 535 women where it was unplanned (42.6% all caesarean deliveries and 24.4% all births). We found no difference in actual mode of birth between groups, (average RR 0.97, 95% CI 0.89 to 1.06) (three trials, 2190 women).Decisional conflict about preferred mode of birth was lower (less uncertainty) for women with decisional support (standardised mean difference (SMD) -0.25, 95% CI -0.47 to -0.02; two trials, 787 women; I² = 48%). There was also a significant increase in knowledge among women with decision support compared with those in the control group (SMD 0.74, 95% CI 0.46 to 1.03; two trials, 787 women; I² = 65%). However, there was considerable heterogeneity between the two studies contributing to this outcome ( I² = 65%) and attrition was greater than 15 per cent and the evidence for this outcome is considered to be moderate quality only. There was no difference in satisfaction between women with decision support and those without it (SMD 0.06, 95% CI -0.09 to 0.20; two trials, 797 women; I² = 0%). No study assessed decisional regret or whether women's information needs were met.Qualitative data gathered in interviews with women and health professionals provided information about acceptability of the decision support and its feasibility of implementation. While women liked the decision support there was concern among health professionals about their impact on their time and workload. Evidence is limited to independent and mediated decision supports. Research is needed on shared decision support interventions for women considering mode of birth in a pregnancy after a caesarean birth to use with their care providers.

Quality of radiotherapy reporting in randomized controlled trials of prostate cancer.

PubMed

Soon, Yu Yang; Chen, Desiree; Tan, Teng Hwee; Tey, Jeremy

2018-06-07

Good radiotherapy reporting in clinical trials of prostate radiotherapy is important because it will allow accurate reproducibility of radiotherapy treatment and minimize treatment variations that can affect patient outcomes. The aim of our study is to assess the quality of prostate radiotherapy (RT) treatment reporting in randomized controlled trials in prostate cancer. We searched MEDLINE for randomized trials of prostate cancer, published from 1996 to 2016 and included prostate RT as one of the intervention arms. We assessed if the investigators reported the ten criteria adequately in the trial reports: RT dose prescription method; RT dose-planning procedures; organs at risk (OAR) dose constraints; target volume definition, simulation procedures; treatment verification procedures; total RT dose; fractionation schedule; conduct of quality assurance (QA) as well as presence or absence of deviations in RT treatment planning and delivery. We performed multivariate logistic regression to determine the factors that may influence the quality of reporting. We found 59 eligible trials. There was significant variability in the quality of reporting. Target volume definition, total RT dose and fractionation schedule were reported adequately in 97% of included trials. OAR constraints, simulation procedures and presence or absence of deviations in RT treatment planning and delivery were reported adequately in 30% of included trials. Twenty-four trials (40%) reported seven criteria or more adequately. Multivariable logistic analysis showed that trials that published their quality assurance results and cooperative group trials were more likely to have adequate quality in reporting in at least seven criteria. There is significant variability in the quality of reporting on prostate radiotherapy treatment in randomized trials of prostate cancer. We need to have consensus guidelines to standardize the reporting of radiotherapy treatment in randomized trials.

Motivational interviewing and screening colonoscopy in high-risk individuals. A randomized controlled trial.

PubMed

Salimzadeh, Hamideh; Khabiri, Roghaye; Khazaee-Pool, Maryam; Salimzadeh, Somayeh; Delavari, Alireza

2018-06-01

To measure the impact of motivational interviewing (MI) on cancer knowledge and screening practice among first degree relatives (FDRs) of patients with colon cancer. This randomized controlled trial targeted patients with colon cancer first to recruit their possible FDRs. Digit randomization of the eligible index patients into intervention or control groups resulted in allocating their belonging FDRs to the same study arm. FDRs (n = 120) in intervention arm received MI counseling on phone by a trained oncology nurse and FDRs (n = 120) in control group received standard generic information by a physician on phone. Primary outcome was the rate of documented colonoscopy in FDRs within six months after the baseline. A total of 227 FDRs were followed up, 115 in the intervention and 112 in the control group. At follow-up, the uptake of screening colonoscopy in the intervention group was 83.5% versus 48.2% in controls (crude odds ratio, 5.4; 95% confidence interval, 2.9-10.0, P < .001). This was the first randomized controlled trial in Iran that confirmed the efficaciousness of a phone-based MI counseling in improving colonoscopy uptake among family members of patients with colon cancer. Phone-based motivational counseling that involves trained nurses or health providers seems to be feasible approach in Iran health system and enhances screening for colon cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

FIRST-line support for Assistance in Breathing in Children (FIRST-ABC): a multicentre pilot randomised controlled trial of high-flow nasal cannula therapy versus continuous positive airway pressure in paediatric critical care.

PubMed

Ramnarayan, Padmanabhan; Lister, Paula; Dominguez, Troy; Habibi, Parviz; Edmonds, Naomi; Canter, Ruth R; Wulff, Jerome; Harrison, David A; Mouncey, Paul M; Peters, Mark J

2018-06-04

Although high-flow nasal cannula therapy (HFNC) has become a popular mode of non-invasive respiratory support (NRS) in critically ill children, there are no randomised controlled trials (RCTs) comparing it with continuous positive airway pressure (CPAP). We performed a pilot RCT to explore the feasibility, and inform the design and conduct, of a future large pragmatic RCT comparing HFNC and CPAP in paediatric critical care. In this multi-centre pilot RCT, eligible patients were recruited to either Group A (step-up NRS) or Group B (step-down NRS). Participants were randomised (1:1) using sealed opaque envelopes to either CPAP or HFNC as their first-line mode of NRS. Consent was sought after randomisation in emergency situations. The primary study outcomes were related to feasibility (number of eligible patients in each group, proportion of eligible patients randomised, consent rate, and measures of adherence to study algorithms). Data were collected on safety and a range of patient outcomes in order to inform the choice of a primary outcome measure for the future RCT. Overall, 121/254 eligible patients (47.6%) were randomised (Group A 60%, Group B 44.2%) over a 10-month period (recruitment rate for Group A, 1 patient/site/month; Group B, 2.8 patients/site/month). In Group A, consent was obtained in 29/33 parents/guardians approached (87.9%), while in Group B 84/118 consented (71.2%). Intention-to-treat analysis included 113 patients (HFNC 59, CPAP 54). Most reported adverse events were mild/moderate (HFNC 8/59, CPAP 9/54). More patients switched treatment from HFNC to CPAP (Group A: 7/16, 44%; Group B: 9/43, 21%) than from CPAP to HFNC (Group A: 3/13, 23%; Group B: 5/41, 12%). Intubation occurred within 72 h in 15/59 (25.4%) of HFNC patients and 10/54 (18.5%) of CPAP patients (p = 0.38). HFNC patients experienced fewer ventilator-free days at day 28 (Group A: 19.6 vs. 23.5; Group B: 21.8 vs. 22.2). Our pilot trial confirms that, following minor changes to consent procedures and treatment algorithms, it is feasible to conduct a large national RCT of non-invasive respiratory support in the paediatric critical care setting in both step-up and step-down NRS patients. clinicaltrials.gov, NCT02612415 . Registered on 23 November 2015.

The exclusion from welfare benefits: Resentment and survey attrition in a randomized controlled trial in Mexico.

PubMed

Stecklov, Guy; Weinreb, Alexander; Winters, Paul

2016-11-01

Public policy programs must often impose limits on who may be eligible for benefits. Despite research on the impact of exclusion in developed countries, there is little evidence on how people react to being excluded from benefits in developing societies. Utilizing repeated waves of data from an experimental evaluation of Mexico's foundational PROGRESA antipoverty program, we examine the impact of exclusion and distinguish two separate forms. "Statistical exclusion" occurs where determination of benefits is based on randomized assignment to a treatment and control group. "Needs-based exclusion" occurs when benefits programs are designed to be selective rather than universal, basing eligibility on characteristics, like relative poverty, that are difficult to measure simply and accurately. Focusing on temporal variation in survey non-response as our behavioral outcome, we show that needs-based exclusion has much greater negative effects on continued participation than statistical exclusion. We also show that these effects are concentrated among the wealthy, that is, those furthest from the eligibility cut-off line. These findings reinforce general concerns about the validity of evaluation studies when incentives are at work. We discuss both the behavioral explanations that might underlie these findings as well as some potential approaches to reduce threats to evaluation validity. Copyright © 2016 Elsevier Inc. All rights reserved.

Prescribed computer games in addition to occlusion versus standard occlusion treatment for childhood amblyopia: a pilot randomised controlled trial.

PubMed

Tailor, Vijay K; Glaze, Selina; Khandelwal, Payal; Davis, Alison; Adams, Gillian G W; Xing, Wen; Bunce, Catey; Dahlmann-Noor, Annegret

2015-01-01

Amblyopia ("lazy eye") is the commonest vision deficit in children. If not fully corrected by glasses, amblyopia is treated by patching or blurring the better-seeing eye. Compliance with patching is often poor. Computer-based activities are increasingly topical, both as an adjunct to standard treatment and as a platform for novel treatments. Acceptability by families has not been explored, and feasibility of a randomised controlled trial (RCT) using computer games in terms of recruitment and treatment acceptability is uncertain. We carried out a pilot RCT to test whether computer-based activities are acceptable and accessible to families and to test trial methods such as recruitment and retention rates, randomisation, trial-specific data collection tools and analysis. The trial had three arms: standard near activity advice, Eye Five, a package developed for children with amblyopia, and an off-the-shelf handheld games console with pre-installed games. We enrolled 60 children age 3-8 years with moderate or severe amblyopia after completion of optical treatment. This trial was registered as UKCRN-ID 11074. Pre-screening of 3600 medical notes identified 189 potentially eligible children, of whom 60 remained eligible after optical treatment, and were enrolled between April 2012 and March 2013. One participant was randomised twice and withdrawn from the study. Of the 58 remaining, 37 were boys. The mean (SD) age was 4.6 (1.7) years. Thirty-seven had moderate and 21 severe amblyopia. Three participants were withdrawn at week 6, and in total, four were lost to follow-up at week 12. Most children and parents/carers found the study procedures, i.e. occlusion treatment, usage of the allocated near activity and completion of a study diary, easy. The prescribed cumulative dose of near activity was 84 h at 12 weeks. Reported near activity usage numbers were close to prescribed numbers in moderate amblyopes (94 % of prescribed) but markedly less in severe amblyopes (64 %). Reported occlusion usage at 12 weeks was 90 % of prescribed dose for moderate and 33 % for severe amblyopes. Computer-based games and activities appear acceptable to families as part of their child's amblyopia treatment. Trial methods were appropriate and accepted by families.

Sodium-glucose co-transporter 2 inhibitors in addition to insulin therapy for management of type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

PubMed

Tang, Huilin; Cui, Wei; Li, Dandan; Wang, Tiansheng; Zhang, Jingjing; Zhai, Suodi; Song, Yiqing

2017-01-01

Given inconsistent trial results of sodium-glucose cotransporter 2 (SGLT2) inhibitors in addition to insulin therapy for treating type 2 diabetes mellitus (T2DM), a meta-analysis was performed to evaluate the efficacy and safety of this combination for T2DM by searching available randomized trials from PubMed, Embase, CENTRAL and ClinicalTrials.gov. Our meta-analysis included seven eligible placebo-controlled trials involving 4235 patients. Compared with placebo, SGLT2 inhibitor treatment was significantly associated with a mean reduction in HbA1c of -0.56%, fasting plasma glucose of -0.95 mmol/L, body weight of -2.63 kg and insulin dose of -8.79 IU, but an increased risk of drug-related adverse events by 36%, urinary tract infections by 29% and genital infections by 357%. No significant increase was observed in risk of overall adverse events [risk ratio (RR), 1.00], serious adverse events (RR, 0.90), adverse events leading to discontinuation (RR, 1.16), hypoglycaemia events (RR, 1.07) and severe hypoglycaemia events (RR, 1.24). No diabetic ketoacidosis events were reported. Further studies are needed to establish optimal combination type and dose. © 2016 John Wiley & Sons Ltd.

The use of ice in the treatment of acute soft-tissue injury: a systematic review of randomized controlled trials.

PubMed

Bleakley, Chris; McDonough, Suzanne; MacAuley, Domhnall

2004-01-01

There are wide variations in the clinical use of cryotherapy, and guidelines continue to be made on an empirical basis. Systematic review assessing the evidence base for cryotherapy in the treatment of acute soft-tissue injuries. A computerized literature search, citation tracking, and hand searching were carried out up to April 2002. Eligible studies were randomized-controlled trials describing human subjects recovering from acute soft-tissue injuries and employing a cryotherapy treatment in isolation or in combination with other therapies. Two reviewers independently assessed the validity of included trials using the Physiotherapy Evidence Database (PEDro) scale. Twenty-two trials met the inclusion criteria. There was a mean PEDro score of 3.4 out of of 10. There was marginal evidence that ice plus exercise is most effective, after ankle sprain and postsurgery. There was little evidence to suggest that the addition of ice to compression had any significant effect, but this was restricted to treatment of hospital inpatients. Few studies assessed the effectiveness of ice on closed soft-tissue injury, and there was no evidence of an optimal mode or duration of treatment. Many more high-quality trials are needed to provide evidence-based guidelines in the treatment of acute soft-tissue injuries.

Effectiveness of training in evidence-based medicine skills for healthcare professionals: a systematic review.

PubMed

Hecht, Lars; Buhse, Susanne; Meyer, Gabriele

2016-04-04

Basic skills in evidence-based medicine (EbM) are indispensable for healthcare professionals to promote consumer-centred, evidence-based treatment. EbM training courses are complex interventions - a fact that has not been methodologically reflected by previous systematic reviews. This review evaluates the effects of EbM training for healthcare professionals as well as the quality of reporting of such training interventions. We searched PubMed, EMBASE, CINAHL, Cochrane Library, ERIC, Campbell Library and PsycINFO up to 9/2014. Randomised controlled trials, controlled clinical trials as well as before-after trials were included. Authors were contacted in order to obtain missing data. Two independent reviewers extracted data and assessed risk of bias. We reviewed 14.507 articles; n = 61 appeared potentially eligible; n = 13 involving 1,120 participants were included. EbM training shows some impact on knowledge and skills, whereas the impact on practical EbM application remains unclear. Risk of bias of included trials raises uncertainty about the effects. Description of complex interventions was poor. EbM training has some positive effects on knowledge and skills of healthcare professionals. Appropriate methods for development, piloting, evaluation, reporting and implementation of the training should be applied.

Prostate cancer, comorbidity, and participation in randomized controlled trials of therapy.

PubMed

Chao, Herta H; Mayer, Tina; Concato, John; Rose, Michal G; Uchio, Edward; Kelly, Wm Kevin

2010-03-01

Randomized controlled trials (RCTs) evaluate the potential benefits of chemotherapy regimens and guide clinical care for patients with cancer. Inclusion criteria for RCTs are usually stringent and may exclude many patients seen in clinical practice. Our objective was to determine the proportion of men with castrate-resistant prostate cancer (CRPC) in a clinical setting that would have been excluded from major phase 3 RCTs. We reviewed eligibility criteria from 24 phase 3 clinical trials evaluating chemotherapy for CRPC active from January, 2004, through April, 2008. We created a common list of criteria used in at least 3 studies and separately considered the criteria from a prominent RCT (TAX 327). We applied these criteria to a population of patients with CRPC treated during 2004 to 2006 at the Veterans Affairs Connecticut Healthcare System. Among 106 patients with CRPC, 99 (93%) had complete medical records, and 45 (45%) of the 99 would have been excluded from RCTs. Common reasons for exclusion were abnormal laboratory values, other malignancies, and other serious medical conditions including cardiac disease. Almost half of the CRPC patients examined in a clinical setting would have been ineligible for phase 3 RCTs, highlighting that such trials may not be applicable to general oncology practice.

Factors influencing enrollment of African Americans in the Look AHEAD trial

USDA-ARS?s Scientific Manuscript database

Many factors have been identified that influence the recruitment of African Americans into clinical trials; however, the influence of eligibility criteria may not be widely appreciated. We used the experience from the Look AHEAD (Action for Health in Diabetes) trial screening process to examine the ...

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.

DeLLITE Depression in late life: an intervention trial of exercise. Design and recruitment of a randomised controlled trial

PubMed Central

Kerse, Ngaire; Falloon, Karen; Moyes, Simon A; Hayman, Karen J; Dowell, Tony; Kolt, Gregory S; Elley, C Raina; Hatcher, Simon; Peri, Kathy; Keeling, Sally; Robinson, Elizabeth; Parsons, John; Wiles, Janine; Arroll, Bruce

2008-01-01

Background Physical activity shows potential in combating the poor outcomes associated with depression in older people. Meta-analyses show gaps in the research with poor trial design compromising certainty in conclusions and few programmes showing sustained effects. Methods/design The Depression in Late Life: an Intervention Trial of Exercise (DeLLITE) is a 12 month randomised controlled trial of a physical activity intervention to increase functional status in people aged 75 years and older with depressive symptoms. The intervention involves an individualised activity programme based on goal setting and progression of difficulty of activities delivered by a trained nurse during 8 home visits over 6 months. The control group received time matched home visits to discuss social contacts and networks. Baseline, 6 and 12 months measures were assessed in face to face visits with the primary outcome being functional status (SPPB, NEADL). Secondary outcomes include depressive symptoms (Geriatric Depression Scale), quality of life (SF-36), physical activity (AHS Physical Activity Questionnaire) and falls (self report). Discussion Due to report in 2008 the DeLLITE study has recruited 70% of those eligible and tests the efficacy of a home based, goal setting physical activity programme in improving function, mood and quality of life in older people with depressive symptomatology. If successful in improving function and mood this trial could prove for the first time that there are long term health benefit of physical activity, independent of social activity, in this high risk group who consume excess health related costs. Trial registration Australian and New Zealand Clinical Trials Register ACTRN12605000475640 PMID:18501008

The Mortality Risk of Conventional Antipsychotics in Elderly Patients: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials.

PubMed

Hulshof, Tessa A; Zuidema, Sytse U; Ostelo, Raymond W J G; Luijendijk, Hendrika J

2015-10-01

Numerous observational studies have reported an increased risk of mortality for conventional antipsychotics in elderly patients, and for haloperidol in particular. Subsequently, health authorities have warned against use of conventional antipsychotics in dementia. Experimental evidence is lacking. To assess the mortality risk of conventional antipsychotics in elderly patients with a meta-analysis of trials. Original studies were identified in electronic databases, online trial registers, and hand-searched references of published reviews. Two investigators found 28 potentially eligible studies, and they selected 17 randomized placebo-controlled trials in elderly patients with dementia, delirium, or a high risk of delirium. Two investigators independently abstracted trial characteristics and deaths, and 3 investigators assessed the risk of bias. Deaths were pooled with RevMan to obtain risk differences and risk ratios. Data of 17 trials with a total of 2387 participants were available. Thirty-two deaths occurred. The pooled risk difference of 0.1% was not statistically significant (95% confidence interval (CI) -1.0%-1.2%). The risk ratio was 1.07 (95% CI 0.54-2.13). Eleven of 17 trials tested haloperidol (n = 1799). The risk difference was 0.4% (95% CI -0.9%-1.6%), the risk ratio was 1.25 (95% CI 0.59-2.65). This meta-analysis of placebo-controlled randomized trials does not show that conventional antipsychotics in general or haloperidol in particular increase the risk of mortality in elderly patients. It questions the observational findings and the warning based on these findings. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Effectiveness of a Peer Support Programme versus Usual Care in Disease Management of Diabetes Mellitus Type 2 regarding Improvement of Metabolic Control: A Cluster-Randomised Controlled Trial.

PubMed

Johansson, Tim; Keller, Sophie; Winkler, Henrike; Ostermann, Thomas; Weitgasser, Raimund; Sönnichsen, Andreas C

2016-01-01

Testing the effectiveness of peer support additionally to a disease management programme (DMP) for type 2 diabetes patients. Unblinded cluster-randomised controlled trial (RCT) involving 49 general practices, province of Salzburg, Austria. All patients enrolled in the DMP were eligible, n = 337 participated (intervention: 148 in 19 clusters; control: 189 in 20 clusters). The peer support intervention ran over 24 months and consisted of peer supporter recruitment and training, and group meetings weekly for physical exercise and monthly for discussion of diabetes related topics. At two-year follow-up, adjusted analysis revealed a nonsignificant difference in HbA1c change of 0.14% (21.97 mmol/mol) in favour of the intervention (95% CI -0.08 to 0.36%, p = 0.22). Baseline values were 7.02 ± 1.25% in the intervention and 7.08 ± 1.25 in the control group. None of the secondary outcome measures showed significant differences except for improved quality of life (EQ-5D-VAS) in controls (4.3 points on a scale of 100; 95% CI 0.08 to 8.53, p = 0.046) compared to the intervention group. Our peer support intervention as an additional DMP component showed no significant effect on HbA1c and secondary outcome measures. Further RTCs with a longer follow-up are needed to reveal whether peer support will have clinically relevant effects. This trial has been registered with Current Controlled Trials Ltd. (ISRCTN10291077).

Angiotensin-converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction: an overview of long-term randomized controlled trials.

PubMed

Danchin, Nicolas; Cucherat, Michel; Thuillez, Christian; Durand, Eric; Kadri, Zena; Steg, Philippe G

2006-04-10

Results of randomized trials of angiotensin-converting enzyme inhibitors in patients with coronary artery disease (CAD) and preserved left ventricular function are conflicting. We undertook this study to determine whether long-term prescription of angiotensin-converting enzyme inhibitors decreases major cardiovascular events and mortality in patients who have CAD and no evidence of left ventricular systolic dysfunction. We searched MEDLINE, EMBASE, and IPA databases, the Cochrane Controlled Trials Register (1990-2004), and reports from scientific meetings (2003-2004), and we reviewed secondary sources. Search terms included angiotensin-converting enzyme inhibitors, coronary artery disease, randomi(s)zed controlled trials, clinical trials, and myocardial infarction. Eligible studies included randomized controlled trials in patients who had CAD and no heart failure or left ventricular dysfunction, with follow-up omicronf 2 years or longer. Of 1146 publications screened, 7 met our selection criteria and included a total of 33 960 patients followed up for a mean of 4.4 years. Five trials included only patients with documented CAD. One trial included patients with documented CAD (80%) or patients who had diabetes mellitus and 1 or more additional risk factors, and another trial included patients who had CAD, a history of transient ischemic attack, or intermittent claudication. Treatment with angiotensin-converting enzyme inhibitors decreased overall mortality (odds ratio, 0.86; 95% confidence interval, 0.79-0.93), cardiovascular mortality (odds ratio, 0.81; 95% confidence interval, 0.73-0.90), myocardial infarction (odds ratio, 0.82; 95% confidence interval, 0.75-0.89), and stroke (odds ratio, 0.77; 95% confidence interval, 0.66-0.88). Other end points, including resuscitation after cardiac arrest, myocardial revascularization, and hospitalization because of heart failure, were also reduced. Angiotensin-converting enzyme inhibitors reduce total mortality and major cardiovascular end points in patients who have CAD and no left ventricular systolic dysfunction or heart failure.

The feasibility and acceptability of conducting a trial of specialist medical care and the Lightning Process in children with chronic fatigue syndrome: feasibility randomized controlled trial (SMILE study)

PubMed Central

2013-01-01

Background Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is relatively common in children with limited evidence for treatment. The Phil Parker Lightning Process (LP) is a trademarked intervention, which >250 children use annually. There are no reported studies investigating the effectiveness or possible side effects of LP. Methods The trial population was drawn from the Bath and Bristol NHS specialist paediatric CFS or ME service. The study was designed as a pilot randomized trial with children (aged 12 to 18 years) comparing specialist medical care with specialist medical care plus the Lightning Process. Integrated qualitative methodology was used to explore the feasibility and acceptability of the recruitment, randomization and interventions. Results A total of 56 children were recruited from 156 eligible children (1 October 2010 to 16 June 2012). Recruitment, randomization and both interventions were feasible and acceptable. Participants suggested changes to improve feasibility and acceptability and we incorporated the following in the trial protocol: stopped collecting 6-week outcomes; introduced a second reminder letter; used phone calls to collect primary outcomes from nonresponders; informed participants about different approaches of each intervention and changed our recommendation for the primary outcome for the full study from school attendance to disability (SF-36 physical function subscale) and fatigue (Chalder Fatigue Scale). Conclusions Conducting randomized controlled trials (RCTs) to investigate an alternative treatment such as LP is feasible and acceptable for children with CFS or ME. Feasibility studies that incorporate qualitative methodology enable changes to be made to trial protocols to improve acceptability to participants. This is likely to improve recruitment rate and trial retention. Trial registration Feasibility study first randomization: 29 September 2010. Trial registration: Current Controlled Trials ISRCTN81456207 (31 July 2012). Full trial first randomization: 19 September 2012. PMID:24304689

"Open mesh" or "strictly selected population" recruitment? The experience of the randomized controlled MeMeMe trial.

PubMed

Cortellini, Mauro; Berrino, Franco; Pasanisi, Patrizia

2017-01-01

Among randomized controlled trials (RCTs), trials for primary prevention require large samples and long follow-up to obtain a high-quality outcome; therefore the recruitment process and the drop-out rates largely dictate the adequacy of the results. We are conducting a Phase III trial on persons with metabolic syndrome to test the hypothesis that comprehensive lifestyle changes and/or metformin treatment prevents age-related chronic diseases (the MeMeMe trial, EudraCT number: 2012-005427-32, also registered on ClinicalTrials.gov [NCT02960711]). Here, we briefly analyze and discuss the reasons which may lead to participants dropping out from trials. In our experience, participants may back out of a trial for different reasons. Drug-induced side effects are certainly the most compelling reason. But what are the other reasons, relating to the participants' perception of the progress of the trial which led them to withdraw after randomization? What about the time-dependent drop-out rate in primary prevention trials? The primary outcome of this analysis is the point of drop-out from trial, defined as the time from the randomization date to the withdrawal date. Survival functions were non-parametrically estimated using the product-limit estimator. The curves were statistically compared using the log-rank test ( P =0.64, not significant). Researchers involved in primary prevention RCTs seem to have to deal with the paradox of the proverbial "short blanket syndrome". Recruiting only highly motivated candidates might be useful for the smooth progress of the trial but it may lead to a very low enrollment rate. On the other hand, what about enrolling all the eligible subjects without considering their motivation? This might boost the enrollment rate, but it can lead to biased results on account of large proportions of drop-outs. Our experience suggests that participants do not change their mind depending on the allocation group (intervention or control). There is no single answer to sort out the short blanket syndrome.

Use of IMMPACT domains in clinical trials of acupuncture for chronic pain: a protocol for a methodological survey.

PubMed

Mazzei, Lauren Giustti; Bergamaschi, Cristiane de Cássia; Silva, Marcus Tolentino; Lopes, Luciane Cruz

2017-09-27

Pain is one of the most common and most debilitating complaints among patients. It affects the individual, their relationship with friends and family, their ability to function at work, and their sociability. Acupuncture is one of the therapeutic resources for managing chronic pain. Given the variability of outcome measures in controlled randomised clinical trials on non-oncologicchronic pain (CRCT-NOCP), the Initiative in Methods, Measurements and Pain Assessment in Clinical Trials (IMMPACT) recommends six domains to be covered in evaluating the effectiveness of treatments for chronic pain. To check whether the methodological quality of outcome reporting in published trials has used IMMPACT recommendations in measuring CRCT-NOCP outcomes when acupuncture was used as a treatment. This is a methodological study. We will systematically search for eligible studies in specific databases with a defined strategy. We will use the MeSHterms of 'acupuncture', 'chronic pain' and similar terms, without restrictions on idiom. Eligible studies will include those which are randomised and chose NOCP patients to be treated with acupuncture or control (sham acupuncture or no acupuncture), recruited after September 2004, with ≥100 patients. The measured outcomes are to be the presence of outcome domains recommended by IMMPACT, domains reported by the patient or clinician, tools used to measure such domains, as well as other features of the studies. We shall conduct a regression analysis to explore factors which can be associated with the presence of outcome domains according to IMMPACT recommendations. This survey will be submitted for presentation at congresses and for publication in a scientific journal. The findings obtained in this study will allow us to measure the quality of the evidence and provide greater transparency in decisions regarding the use of acupuncture as a viable alternative to managing chronic pain. © 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.

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.

A multi-centre, randomised controlled trial of cognitive therapy to prevent harmful compliance with command hallucinations.

PubMed

Birchwood, Max; Peters, Emmanuelle; Tarrier, Nicholas; Dunn, Graham; Lewis, Shon; Wykes, Til; Davies, Linda; Lester, Helen; Michail, Maria

2011-09-30

Command hallucinations are among the most distressing, high risk and treatment resistant symptoms for people with psychosis; however, currently, there are no evidence-based treatment options available for this group. A cognitive therapy grounded in the principles of the Social Rank Theory, is being evaluated in terms of its effectiveness in reducing harmful compliance with command hallucinations. This is a single blind, intention-to-treat, multi-centre, randomized controlled trial comparing Cognitive Therapy for Command Hallucinations + Treatment as Usual with Treatment as Usual alone. Eligible participants have to fulfil the following inclusion criteria: i) ≥16 years; ii) ICD-10 diagnosis of schizophrenia or related disorder; iii) command hallucinations for at least 6 months leading to risk of harm to self or others. Following the completion of baseline assessments, eligible participants will be randomly allocated to either the Cognitive Therapy for Command Hallucinations + Treatment as Usual group or the Treatment as Usual group. Outcome will be assessed at 9 and 18 months post randomization with assessors blind to treatment allocation. The primary outcome is compliance behaviour and secondary outcomes include beliefs about voices' power, distress, psychotic symptoms together with a health economic evaluation. Qualitative interviews with services users will explore the acceptability of Cognitive Therapy for Command Hallucinations. Cognitive behaviour therapy is recommended for people with psychosis; however, its focus and evaluation has primarily revolved around the reduction of psychotic symptoms. In this trial, however, the focus of the cognitive behavioural intervention is on individuals' appraisals, behaviour and affect and not necessarily symptoms; this is also reflected in the outcome measures used. If successful, the results will mark a significant breakthrough in the evidence base for service users and clinicians and will provide a treatment option for this group where none currently exist. The trial will open the way for further breakthrough work with the 'high risk' population of individuals with psychosis, which we would intend to pursue. ISRCTN: ISRCTN62304114.

Antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease: protocol of a randomised controlled proof-of-concept trial (APPLE COPD-ICON 2).

PubMed

Kunadian, Vijay; Chan, Danny; Ali, Hani; Wilkinson, Nina; Howe, Nicola; McColl, Elaine; Thornton, Jared; von Wilamowitz-Moellendorff, Alexander; Holstein, Eva-Maria; Burns, Graham; Fisher, Andrew; Stocken, Deborah; De Soyza, Anthony

2018-05-26

The antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease (APPLE COPD-ICON2) trial is a prospective 2×2 factorial, double-blinded proof-of-concept randomised controlled trial targeting patients with chronic obstructive pulmonary disease (COPD) at high risk of cardiovascular disease. The primary goal of this trial is to investigate if treatment with antiplatelet therapy will produce the required response in platelet function measured using the Multiplate test in patients with COPD. Patients with COPD are screened for eligibility using inclusion and exclusion criteria. Eligible patients are randomised and allocated into one of four groups to receive aspirin plus placebo, ticagrelor plus placebo, aspirin plus ticagrelor or placebo only. Markers of systemic inflammation, platelet reactivity, arterial stiffness, carotid intima-media thickness (CIMT), lung function and quality of life questionnaires are assessed. The primary outcome consists of inhibition (binary response) of aspirin and ADP-induced platelet function at 6 months. Secondary outcomes include changes in inflammatory markers, CIMT, non-invasive measures of vascular stiffness, quality of life using questionnaires (EuroQol-five dimensions-five levels of perceived problems (EQ5D-5L), St. George's COPD questionnaire) and to record occurrence of repeat hospitalisation, angina, myocardial infarction or death from baseline to 6 months. Safety outcomes will be rates of major and minor bleeding, forced expiratory volume in 1 s, forced vital capacity and Medical Research Council dyspnoea scale. The study was approved by the North East-Tyne and Wear South Research Ethics Committee (15/NE/0155). Findings of the study will be presented in scientific sessions and published in peer-reviewed journals. ISRCTN43245574; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.