Introduction Physical activity (PA) is critical for disease prevention and maintaining functional ability with aging. Despite this, as many as 50% of older adults in populations worldwide are considered insufficiently active. There is a recognized need to mobilize policies targeted toward modifiable determinants of healthy aging like PA. This umbrella review aimed to summarize the evidence for determinants of PA in community-dwelling older adults. Methods A research librarian searched six databases. Systematic and scoping reviews were included if they investigated community-dwelling people with a mean age of 60 + years and examined a relationship between a determinant and any type of PA. Two independent reviewers screened and extracted data from all reviews. JBI methodology and Critical Appraisal Checklist for Systematic Reviews and Research Syntheses were followed and information on the quality of the evidence was extracted. Results From 17,277 records screened,11 reviews representing > 300 unique primary papers were ultimately included. Only 6% of studies included in all reviews had longitudinal designs. Included studies used a large variety of PA measures, with 76% using only self-report, 15% using only direct measures (e.g., accelerometry), 3% using both types, and 6% with no outcome measure reported. Only four reviews provided a definition of PA and there was substantial inconsistency in the way PA was categorised. Community level influences, which only included the physical environment, were the most commonly assessed (6/11) with more than 70% of the summarized relationships demonstrating null associations. Three out of four reviews reported a positive relationship between walkability and PA in general community-dwelling older adults. There was also evidence supporting relationships between presence of social support for PA, younger age, and men having higher PA from a single systematic review. None of the included reviews assessed the quality of evidence but over 60% performed a risk of bias assessment. Conclusions Walkability, age, gender, and social support for PA were the most supported PA determinants identified. Further research should focus on interpersonal and intrapersonal influences and incorporate direct measures of PA with clear operational definitions. There is a need for longitudinal study designs to further understand determinants of PA behaviour trajectories.

BACKGROUND:Black Canadians experience poor health care, poor health outcomes, and a greater burden of health inequalities, much of which is rooted in the unequal distribution of social determinants of health. Despite Canada's emphasis on social inclusion, Canada's Black population faces substantial social inequities that affect their health and well-being. These disparities may specifically be attributed to racial discrimination, immigration status, precarious housing, underemployment, and increased poverty among Black Canadians. OBJECTIVE:This paper describes a protocol for a scoping review that aims to understand the range and nature of research conducted on the health of Black Canadians as well as the gaps in this literature. METHODS:Arksey and O'Malley's methodological framework guided the conduct of the scoping review. We searched electronic databases (CINAHL, Embase, Global Health, MEDLINE, PsycINFO, Scopus, Sociological Abstracts, and Web of Science) and grey literature sources for peer-reviewed articles and grey reports on the health of Black Canadians. Six reviewers independently screened the abstracts and full text of studies to determine eligibility for inclusion. According to the PRISMA-ScR (Preferred Reporting Items for Systematics Reviews and Meta-Analyses extension for Scoping Reviews) guidelines, the findings will be synthesized quantitatively and qualitatively through thematic analysis. RESULTS:Title, abstract, and full-text screening concluded in October 2022. Data collection is in progress and is expected to be completed by April 2023. Data analysis and drafting of the manuscript will be done thereafter. Findings from the scoping review are expected to be provided for peer review in 2023. CONCLUSIONS:This review will collect important data and evidence related to the health (mental, reproductive, and sexual; social determinants of health) of the Black population in Canada. The findings could help identify existing gaps in the health of Black individuals in Canada and inform future research paradigms. The findings will further inform the development of a knowledge hub on Black Canadians' health. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):PRR1-10.2196/42212.

Background During the COVID-19 pandemic, there was a necessity for eating disorder (ED) outpatient treatment to be delivered virtually. Given this transition, and the surge in new ED cases, there was an urgent need to investigate virtually delivered ED prevention programs. This review aimed to identify the available evidence on virtual ED prevention programs for children, adolescents, and emerging adults. Method Using scoping review methodology, seven databases were searched for studies published from January 2000 to April 2021 reporting on virtually delivered ED prevention interventions for children and adolescents (< 18 years) and emerging adults (18-25 years). Studies were excluded if they contained adults (> 25 years) and individuals with clinical ED diagnoses. Abstracts and full-text papers were reviewed independently by two reviewers. Data was extracted on study type, methodology, age, sample size, virtual intervention, outcomes, and results. In April 2022, we used a forward citation chaining process to identify any relevant articles from April 2021 to April 2022. Results Of 5129 unique studies identified, 67 met eligibility criteria, which included asynchronous (n = 35) and synchronous (n = 18) internet-based programs, other e-technology including mobile apps (n = 3) and text messaging interventions (n = 1), computer-based programs (n = 6), and online caregiver interventions focused on child outcomes (n = 4). Few studies mainly included children and adolescents (n = 18), whereas the vast majority included emerging adults (n = 49). For children and adolescents, the most widely researched programs were Student Bodies and its adapted versions (n = 4), eBody Project (n = 2), and Parents Act Now (n = 2). For emerging adults, the most widely researched programs were Student Bodies and its adapted versions (n = 16), eBody Project (n = 6) and Expand Your Horizon (n = 4). These interventions were effective at reducing various symptoms and ED risk. Some studies demonstrated that virtual prevention intervention efficacy resembled in-person delivery. Conclusion Virtual prevention interventions for EDs can be effective, however more research is needed studying their impact on children and adolescents and on improving access for vulnerable groups. Additional efficacy studies are required, such as for text messaging and mobile app ED prevention interventions. Evidence-based recommendations for virtual ED prevention for children, adolescents, and emerging adults at-risk for EDs should be prioritized. Plain English summary This review aimed to identify all available evidence for virtual eating disorder (ED) prevention interventions for children/adolescents (<18 years) and emerging adults (18-25 years). We reviewed seven databases and found 67 studies for inclusion. Findings were summarized into themes: asynchronous (not in real-time) and synchronous (in real-time) internet-based programs, other e-technology (mobile applications ['apps'], text messages), computer-based programs, and online caregiver interventions focused on child outcomes. Among children and adolescents, the most widely researched programs were Student Bodies (asynchronous internet-based cognitive-behavioural program), eBody Project (synchronous internet-based cognitive-dissonance program), and Parents Act Now, (online caregiver intervention). Among emerging adults, the most widely researched programs were Student Bodies (described above), eBody Project (described above) and Expand Your Horizon (asynchronous internet-based body functionality program). These interventions were effective at reducing symptoms and/or risk of developing EDs. Additional research is needed, including a greater focus on children and adolescents, and text messaging, mobile apps, online cognitive restructuring, and online imagery rescripting ED prevention interventions. Evidence-based recommendations for virtual ED prevention interventions that have been reviewed by a panel and research on improving access to virtual ED prevention services for vulnerable groups should also be prioritized.

Abstract Background Although early intervention is crucial in interrupting the development of eating disorders, little is currently known about help-seeking behaviours among individuals experiencing eating disorder symptoms. Given that eating disorders typically begin early in life, it is necessary to investigate the processes employed by children, adolescents, and emerging adults when seeking services for troubling symptoms. This is a growing concern as the COVID-19 pandemic has resulted in an increase in the number of individuals engaging in disordered eating behaviours. This scoping review explores the current state of the literature for evidence on how youth with eating disorder symptoms seek help, with the aim of better understanding how to identify and treat more individuals earlier. Methods Using scoping review methodology, we searched seven databases for studies published from January 2000 to April 2021 that reported on help-seeking attitudes, behaviours, and healthcare utilization patterns for children and adolescents (< 18 years), emerging adults (18–25 years), and a mixture of these groups (< 25 years). Seven thousand, two hundred, and eighteen articles were identified for review. After duplicates were removed, three reviewers independently screened titles and abstracts and reviewed full-text articles. Findings related to help-seeking activity were extracted from the 62 articles that were ultimately included in this scoping review. Results Study findings were summarized into help-seeking patterns (i.e., rates, types) as well as factors ranging from the individual level to society that influenced help-seeking behaviour. Many youth meeting eating disorder criteria were not seeking help. Notable barriers to help-seeking included poor mental health literacy, experiences with healthcare providers who failed to detect and lacked knowledge about eating disorders, minimal support from family and friends, and stigma surrounding eating disorders and help-seeking for mental health concerns. Conclusions The results of this scoping review can be used to inform early intervention and health promotion program development. Future research should focus on the help-seeking attitudes and activities among underrepresented groups with eating disorders (e.g., men, ethnic and gender minorities), the perspectives of family and other supporters in the help-seeking process for youth, and retrospective accounts from adults with lived experience of an eating disorder. Plain English summary Addressing and interrupting eating disorder-related thoughts and behaviours as soon as possible, with the help of a mental health professional, leads to better outcomes for youth struggling with an eating disorder. However, little is known about what prompts youth to talk about their weight, body, or eating concerns with someone—like their parent, friend, teacher, guidance counsellor, or primary care practitioner. This review explores the available published research on help-seeking patterns and preferences among youth with eating disorder concerns. Our team followed a standardized process to find 62 relevant articles for this paper. Of note, many young people who reported eating disorder concerns were not seeking help for themselves. Feeling supported by family and their primary care provider, understanding the signs of an eating disorder, and not feeling shame for reaching out for help reportedly led youth to speak up about their concerns. The findings have clinical implications for learning effective ways to help youth feel safe to speak freely about their eating disorder-related concerns, which enhances the chances of intervening early and catching symptoms before they worsen.

Objective The COVID-19 pandemic has had detrimental effects on mental health. Literature on the impact on individuals with eating disorders is slowly emerging. While outpatient eating disorder services in Canada have attempted to transition to virtual care, guidelines related to optimal virtual care in this field are lacking. As such, the objective of our Canadian Consensus Panel was to develop clinical practice guidelines related to the provision of virtual care for children, adolescents, and emerging adults living with an eating disorder, as well as their caregivers, during the COVID-19 pandemic and beyond. Methods Using scoping review methodology (with literature in databases from 2000 to 2020 and grey literature from 2010 to 2020), the Grading of Recommendations, Assessment, Development, and Evaluation system, the Appraisal of Guidelines, Research and Evaluation tool, and a panel of diverse stakeholders from across Canada, we developed high quality treatment guidelines that are focused on virtual interventions for children, adolescents, and emerging adults with eating disorders, and their caregivers. Results Strong recommendations were supported specifically in favour of in-person medical evaluation when necessary for children, adolescents, and emerging adults, and that equity-seeking groups and marginalized youth should be provided equal access to treatment. For children and adolescents, weak recommendations were supported for telehealth family-based treatment (FBT) and online guided parental self-help FBT. For emerging adults, internet cognitive-behavioural therapy (CBT)-based guided self-help was strongly recommended. Weak recommendations for emerging adults included CBT-based group internet interventions as treatment adjuncts, internet-based relapse prevention Maudsley Model of Anorexia Nervosa Treatment for Adults (MANTRA) guided self-help, telehealth relapse prevention using MANTRA, and guided CBT-based smartphone apps as treatment adjuncts. For caregivers of children and adolescents, weak recommendations were supported for virtual parent meal support training, and moderated online caregiver forums and support groups. For caregivers of emerging adults, guided parental self-help CBT was strongly recommended, and unguided caregiver psychoeducation self-help was weakly recommended. Conclusions Several gaps for future work were identified including the impact of sex, gender, race, and socioeconomic status on virtual care among children, adolescents, and emerging adults with eating disorders, as well as research on more intensive services, such as virtual day hospitals.

Background Randomised trial protocols may incorporate interim analyses, with the potential to stop the study for futility if early data show insufficient promise of a treatment benefit. Previously, we have shown that this approach will theoretically lead to mis-estimation of the treatment effect. We now wished to ascertain the importance of this phenomenon in practice. Methods We reviewed the methods and results in a set of trials that had stopped for futility, identified through an extensive literature search. We recorded clinical areas, interventions, study design, outcomes, trial setting, sponsorship, planned and actual treatment effects, sample sizes; power; and if there was a data safety monitoring board, or a published protocol. We identified: if interim analyses were pre-specified, and how many analyses actually occurred; what pre-specified criteria might define futility; if a futility analysis formed the basis for stopping; who made the decision to stop; and the conditional power of each study, i.e. the probability of statistically significant results if the study were to continue to its complete sample size. Results We identified 52 eligible trials, covering many clinical areas. Most trials had multiple centres, tested drugs, and 40% were industry sponsored. There were 75% where at least one interim analysis was planned a priori; a majority had only one interim analysis, typically with about half the target total sample size. A majority of trials did not pre-define a stopping rule, and a variety of reasons were given for stopping. Few studies calculated and reported low conditional power to justify the early stop. When conditional power could be calculated, it was typically low, especially under the current trend hypothesis. However, under the original design hypothesis, a few studies had relatively high conditional power. Data collection often continued after the interim analysis. Conclusions Although other factors will typically be involved, we conclude that, from the perspective of conditional power, stopping early for futility was probably reasonable in most cases, but documentation of the basis for stopping was often missing or vague. Interpretation of truncated trials would be enhanced by improved reporting of stopping protocols, and of their actual execution.

Jennifer Couturier*1, Danielle Pellegrini1, Catherine Miller2, Neera Bhatnagar1, Ahmed Boachie3, Kerry Bourret4, Melissa Brouwers5, Jennifer S. Coelho6, Gina Dimitropoulos7, Sheri Findlay1, Catherine Ford8, Josie Geller6, Seena Grewal3, Joanne Gusella9, Leanna Isserlin5, Monique Jericho7, Natasha Johnson1, Debra K. Katzman3, Melissa Kimber1, Adele Lafrance10, Anick Leclerc11, Rachel Loewen12, Techiya Loewen13, Gail McVey3, Mark Norris5, David Pilon9, Wendy Preskow14, Wendy Spettigue5, Cathleen Steinegger3, Elizabeth Waite13, Cheryl Webb1

The publisher regrets < Bala, Malgorzata M was missing from the list of authors>. The publisher would like to apologise for any inconvenience caused. A systematic survey identified 36 criteria for assessing effect modification claims in randomized trials or meta-analysesJournal of Clinical EpidemiologyVol. 113PreviewThe objective of the study was to systematically survey the methodological literature and collect suggested criteria for assessing the credibility of effect modification and associated rationales. Full-Text PDF

Background: Evidence with regard to antibiotic prophylaxis for patients with open fractures of the extremities is limited. We therefore conducted a systematic survey addressing current practice and recommendations. Methods: We included publications from January 2007 to June 2017. We searched Embase, MEDLINE, CINAHL, the Cochrane Central Registry of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews for clinical studies and surveys of surgeons; WorldCat for textbooks; and web sites for guidelines and institutional protocols. Results: We identified 223 eligible publications that reported 100 clinical practice patterns and 276 recommendations with regard to systemic antibiotic administration, and 3 recommendations regarding local antibiotic administration alone. Most publications of clinical practice patterns used regimens with both gram-positive and gram-negative coverage and continued the administration for 2 to 3 days. Most publications recommended prophylactic systemic antibiotics. Most recommendations suggested gram-positive coverage for less severe injuries and administration duration of 3 days or less. For more severe injuries, most recommendations suggested broad antimicrobial coverage continued for 2 to 3 days. Most publications reported intravenous administration of antibiotics immediately. Conclusions: Current practice and recommendations strongly support early systemic antibiotic prophylaxis for patients with open fractures of the extremities. Differences in antibiotic regimens, doses, and durations of administration remain in both practice and recommendations. Consensus with regard to optimal practice will likely require well-designed randomized controlled trials. Clinical Relevance: The current survey of literature systematically provides surgeons’ practice and the available expert recommendations from 2007 to 2017 on the use of prophylactic antibiotics in the management of open fractures of extremities.

Background: Evidence with regard to antibiotic prophylaxis for patients with open fractures of the extremities is limited. We therefore conducted a systematic survey addressing current practice and recommendations. Methods: We included publications from January 2007 to June 2017. We searched Embase, MEDLINE, CINAHL, the Cochrane Central Registry of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews for clinical studies and surveys of surgeons; WorldCat for textbooks; and web sites for guidelines and institutional protocols. Results: We identified 223 eligible publications that reported 100 clinical practice patterns and 276 recommendations with regard to systemic antibiotic administration, and 3 recommendations regarding local antibiotic administration alone. Most publications of clinical practice patterns used regimens with both gram-positive and gram-negative coverage and continued the administration for 2 to 3 days. Most publications recommended prophylactic systemic antibiotics. Most recommendations suggested gram-positive coverage for less severe injuries and administration duration of 3 days or less. For more severe injuries, most recommendations suggested broad antimicrobial coverage continued for 2 to 3 days. Most publications reported intravenous administration of antibiotics immediately. Conclusions: Current practice and recommendations strongly support early systemic antibiotic prophylaxis for patients with open fractures of the extremities. Differences in antibiotic regimens, doses, and durations of administration remain in both practice and recommendations. Consensus with regard to optimal practice will likely require well-designed randomized controlled trials. Clinical Relevance: The current survey of literature systematically provides surgeons’ practice and the available expert recommendations from 2007 to 2017 on the use of prophylactic antibiotics in the management of open fractures of extremities.

OBJECTIVE:The objective of the study was to systematically survey the methodological literature and collect suggested criteria for assessing the credibility of effect modification and associated rationales. STUDY DESIGN AND SETTING:We searched MEDLINE, Embase, and WorldCat up to March 2018 for publications providing guidance for assessing the credibility of effect modification identified in randomized trials or meta-analyses. Teams of two investigators independently identified eligible publications and extracted credibility criteria and authors' rationale, reaching consensus through discussion. We created a taxonomy of criteria that we iteratively refined during data abstraction. RESULTS:We identified 150 eligible publications that provided 36 criteria and associated rationales. Frequent criteria included significant test for interaction (n = 54), a priori hypothesis (n = 49), providing a causal explanation (n = 47), accounting for multiplicity (n = 45), testing a small number of effect modifiers (n = 38), and prespecification of analytic details (n = 39). For some criteria, we found more than one rationale; some criteria were connected through a common rationale. For some criteria, experts disagreed regarding their suitability (e.g., added value of stratified randomization; trustworthiness of biologic rationales). CONCLUSION:Methodologists have expended substantial intellectual energy providing criteria for critical appraisal of apparent effect modification. Our survey highlights popular criteria, expert agreement and disagreement, and where more work is needed, including testing criteria in practice.

Importance:Progression-free survival (PFS) has become a commonly used outcome to assess the efficacy of new cancer drugs. However, it is not clear if delay in progression leads to improved quality of life with or without overall survival benefit.Objective:To evaluate the association between PFS and health-related quality of life (HRQoL) in oncology through a systematic review and quantitative analysis of published randomized clinical trials. Eligible trials addressed oral, intravenous, intraperitoneal, or intrapleural chemotherapy or biological treatments, and reported PFS or health-related quality of life.Data Sources:For this systematic review and quantitative analysis of randomized clinical trials of patients with cancer, we searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 2000, through May 4, 2016.Study Selection:Paired reviewers independently screened citations, extracted data, and assessed risk of bias of included studies.Data Extraction and Synthesis:We examined the association of difference in median PFS duration (in months) between treatment groups with difference in global, physical, and emotional HRQoL scores between groups (standardized to a range of 0-100, with higher scores representing better HRQoL) using weighted simple regressions.Main Outcome and Measure:The association between PFS duration and HRQoL.Results:Of 35 960 records screened, 52 articles reporting on 38 randomized clinical trials involving 13 979 patients across 12 cancer types using 6 different HRQoL instruments were included. The mean (SD) difference in median PFS between the intervention and the control arms was 1.91 (3.35) months. The mean (SD) differences in change of HRQoL adjusted to per-month values were -0.39 (3.59) for the global domain, 0.26 (5.56) for the physical domain, and 1.08 (3.49) for the emotional domain. The slope of the association between the difference in median PFS and the difference in change for global HRQoL (n = 30 trials) was 0.12 (95% CI, -0.27 to 0.52); for physical HRQoL (n = 20 trials) it was -0.20 (95% CI, -0.62 to 0.23); and for emotional HRQoL (n = 13 trials) it was 0.78 (95% CI, -0.05 to 1.60).Conclusions and Relevance:We failed to find a significant association between PFS and HRQoL in cancer clinical trials. These findings raise questions regarding the assumption that interventions prolonging PFS also improve HRQoL in patients with cancer. Therefore, to ensure that patients are truly obtaining important benefit from cancer therapies, clinical trial investigators should measure HRQoL directly and accurately, ensuring adequate duration and follow-up.

Ezetimibe is widely used in combination with statins to reduce low-density lipoprotein. We sought to examine the impact of ezetimibe when added to statins on patient-important outcomes. Medline, EMBASE, CINAHL, and CENTRAL were searched through July, 2016. Randomized controlled trials (RCTs) of ezetimibe combined with statins versus statins alone that followed patients for at least 6 months and reported on at least one of all-cause mortality, cardiovascular deaths, non-fatal myocardial infarctions (MI), and non-fatal strokes were included. Pairs of reviewers extracted study data and assessed risk of bias independently and in duplicate. Quality of evidence was assessed using the GRADE approach. We conducted a narrative review with complementary subgroup and sensitivity analyses. IMPROVE-IT study enrolled 93% of all patients enrolled in the 8 included trials. Our analysis of the IMPROVE-IT study results showed that in patients at high risk of cardiovascular events, ezetimibe added to statins was associated with i) a likely reduction in non-fatal MI (17 fewer/1000 treated over 6 years, moderate certainty in evidence); ii) a possible reduction in non-fatal stroke (6 fewer/1000 treated over 6 years, low certainty); iii) no impact on myopathy (moderate certainty); iv) potentially no impact on all-cause mortality and cardiovascular death (both moderate certainty); and v) possibly no impact on cancer (low certainty). Addition of ezetimibe to moderate-dose statins is likely to result in 17 fewer MIs and possibly 6 fewer strokes/1000 treated over 6 years but is unlikely to reduce all-cause mortality or cardiovascular death. Patients who place a high value on a small absolute reduction in MI and are not adverse to use of an additional medication over a long duration may opt for ezetimibe in addition to statin therapy. Our analysis revealed no increased specific harms associated with addition of ezetimibe to statins.

Objectives: Randomized clinical trials (RCTs) are costly. We aimed to provide a systematic overview of the available evidence on resource use and costs for RCTs to support budget planning. Study Design and Setting: We systematically searched MEDLINE, EMBASE, and HealthSTAR from inception until November 30, 2016 without language restrictions. We included any publication reporting empirical data on resource use and costs of RCTs and categorized them depending on whether they reported (i) resource and costs of all aspects at all study stages of an RCT (including conception, planning, preparation, conduct, and all tasks after the last patient has completed the RCT); (ii) on several aspects, (iii) on a single aspect (e.g., recruitment); or (iv) on overall costs for RCTs. Median costs of different recruitment strategies were calculated. Other results (e.g., overall costs) were listed descriptively. All cost data were converted into USD 2017. Results: A total of 56 articles that reported on cost or resource use of RCTs were included. None of the articles provided empirical resource use and cost data for all aspects of an entire RCT. Eight articles presented resource use and cost data on several aspects (e.g., aggregated cost data of different drug development phases, site-specific costs, selected cost components). Thirty-five articles assessed costs of one specific aspect of an RCT (i.e., 30 on recruitment; five others). The median costs per recruited patient were USD 409 (range: USD 41-6,990). Overall costs of an RCT, as provided in 16 articles, ranged from USD 43-103,254 per patient, and USD 0.2-611.5 Mio per RCT but the methodology of gathering these overall estimates remained unclear in 12 out of 16 articles (75%). Conclusion: The usefulness of the available empirical evidence on resource use and costs of RCTs is limited. Transparent and comprehensive resource use and cost data are urgently needed to support budget planning for RCTs and help improve sustainability. (C) 2017 Elsevier Inc. All rights reserved.

Objective To systematically survey existing definitions, concepts, and criteria of clinical research quality, both developed by stakeholder groups as well as in the medical literature. This study serves as a first step in the development of a comprehensive framework for the quality of clinical research. Study design and setting We systematically and in duplicate searched definitions, concepts and criteria of clinical research quality on websites of stakeholders in clinical research until no further insights emerged and in MEDLINE up to February 2015. Stakeholders included governmental bodies, regulatory agencies, the pharmaceutical industry, academic and commercial contract research organizations, initiatives, research ethics committees, patient organizations and funding agencies from 13 countries. Data synthesis involved descriptive and qualitative analyses following the Framework Method on definitions, concepts, and criteria of clinical research quality. Descriptive codes were applied and grouped into clusters to identify common and stakeholder-specific quality themes. Results Stakeholder concepts on how to assure quality throughout study conduct or articles on quality assessment tools were common, generally with no a priori definition of the term quality itself. We identified a total of 20 explicit definitions of clinical research quality including varying quality dimensions and focusing on different stages in the clinical research process. Encountered quality dimensions include ethical conduct, patient safety/rights/priorities, internal validity, precision of results, generalizability or external validity, scientific and societal relevance, transparency and accessibility of information, research infrastructure and sustainability. None of the definitions appeared to be comprehensive either in terms of quality dimensions, research stages, or stakeholder perspectives. Conclusion Clinical research quality is often discussed but rarely defined. A framework defining clinical research quality across stakeholders’ individual perspectives is desirable to facilitate discussion, assessment, and improvement of quality at all stages of clinical research.

Objectives: Prior studies regarding whether single-center trial estimates are larger than multi-center are equivocal. We examined the extent to which single-center trials yield systematically larger effects than multi-center trials.Study Design and Setting: We searched the 119 core clinical journals and the Cochrane Database of Systematic Reviews for meta analyses (MAs) of randomized controlled trials (RCTs) published during 2012. In this meta-epidemiologic study, for binary variables, we computed the pooled ratio of ORs (RORs), and for continuous outcomes mean difference in standardized mean differences (SMDs), we conducted weighted random-effects meta-regression and random-effects MA modeling. Our primary analyses were restricted to MAs that included at least five RCTs and in which at least 25% of the studies used each of single trial center (SC) and more trial center (MC) designs.Results: We identified 81 MAs for the odds ratio (OR) and 43 for the SMD outcome measures. Based on our analytic plan, our primary analysis (core) is based on 25 MAs/241 RCTs (binary outcome) and 18 MAs/173 RCTs (continuous outcome). Based on the core analysis, we found no difference in magnitude of effect between SC and MC for binary outcomes [RORs: 1.02; 95% confidence interval (CI): 0.83, 1.24; I-2 20.2%]. Effect sizes were systematically larger for SC than MC for the continuous outcome measure (mean difference in SMDs: -0.13; 95% CI: -0.21, -0.05; I-2 0%).Conclusions: Our results do not support prior findings of larger effects in SC than MC trials addressing binary outcomes but show a very similar small increase in effect in SC than MC trials addressing continuous outcomes. Authors of systematic reviews would be wise to include all trials irrespective of SC vs. MC design and address SC vs. MC status as a possible explanation of heterogeneity (and consider sensitivity analyses). (C) 2015 Elsevier Inc. All rights reserved.

With the non-medical use of prescription opioids increasingly becoming a method of abuse in Canada, the number of patients requiring methadone maintenance treatment (MMT) for opioid use disorder has increased dramatically. The rate of cannabis use in this population is disproportionately high (~50 %). Because its use is generally perceived as harmless, cannabis use is often not monitored during MMT. Current literature regarding the effects of cannabis use on MMT is conflicting, and the presence and nature of an association has not been clearly established. The primary objective of this review will be to conduct a systematic review of the literature and, if appropriate, a meta-analysis to determine whether there is an association between cannabis use and MMT outcomes. A secondary objective will be to perform subgroup analyses (by age, sex, method of cannabis measurement, and country) to determine whether cannabis use differentially influences MMT outcomes within these subgroups.

Background Light therapy is a known treatment for patients with seasonal affective disorder. However, the efficacy of light therapy in treating patients with non-seasonal depression remains inconclusive. Aims To provide the current state of evidence for efficacy of light therapy in non-seasonal depressive disorders. Method Systematic review of randomised controlled trials (RCTs) was conducted by searching MEDLINE, EMBASE, PsycINFO, CINAHL, and CENTRAL from their inception to September 2015. Study selection, data abstraction and risk of bias assessment were independently conducted in duplicate. Meta-analyses were performed to provide a summary statistic for the included RCTs. The reporting of this systematic review follows the PRISMA guidelines. Results A meta-analysis including 881 participants from 20 RCTs demonstrated a beneficial effect of light therapy in non-seasonal depression (standardised mean difference in depression score −0.41 (95% CI −0.64 to −0.18)). This estimate was associated with significant heterogeneity ( I 2 =60%, P =0.0003) that was not sufficiently explained by subgroup analyses. There was also high risk of bias in the included trials limiting the study interpretation. Conclusions The overall quality of evidence is poor due to high risk of bias and inconsistency. However, considering that light therapy has minimal side-effects and our meta-analysis demonstrated that a significant proportion of patients achieved a clinically significant response, light therapy may be effective for patients with non-seasonal depression and can be a helpful additional therapeutic intervention for depression.

Public health concerns for the independent management of obesity and suicidal behavior are rising. Emerging evidence suggests body weight plays an important role in quantifying the risk of suicide. In light of these findings, we aimed to clarify the association between body mass index (BMI) and suicidal behavior by systematically reviewing and evaluating the literature. Studies were identified by searching MEDLINE, EMBASE, PsycINFO, and CINAHL from inception to January 2015, supplemented by hand and grey literature searches. Study screening, data extraction, and risk of bias assessment were conducted in duplicate. We included 38 observational studies. Meta-analyses supported an inverse association between BMI and completed suicide. Pooled summary estimates demonstrated that underweight was significantly associated with an increased risk of completed suicide (HR = 1.21, 95% CI 1.07 to 1.36, p = .002), and obesity (HR = 0.71, 95% CI 0.56 to 0.89, p = .003) and overweight (HR = 0.78, 95% CI 0.75 to 0.82, p < .0001) were significantly associated with a decreased risk of completed suicide relative to normal weight. A qualitative summary of the literature demonstrated conflicting evidence regarding the association between BMI and attempted suicide and revealed no association between BMI and suicidal ideation. BMI may be used to aid the assessment of suicide risk, especially that of completed suicide. However, unmeasured confounders and systematic biases of individual studies limit the quality of evidence.

Objective Large middle cerebral artery stroke (space-occupying middle-cerebral-artery (MCA) infarction (SO-MCAi)) results in a very high incidence of death and severe disability. Decompressive hemicraniectomy (DHC) for SO-MCAi results in large reductions in mortality; the level of function in the survivors, and implications, remain controversial. To address the controversy, we pooled available randomised controlled trials (RCTs) that examined the impact of DHC on survival and functional ability in patients with large SO-MCAi and cerebral oedema. Methods We searched MEDLINE, EMBASE and Cochrane library databases for randomised controlled trials (RCTs) enrolling patients suffering SO-MCAi comparing conservative management to DHC administered within 96 hours after stroke symptom onset. Outcomes were death and disability measured by the modified Rankin Scale (mRS). We used a random effects meta-analytical approach with subgroup analyses (time to treatment and age). We applied GRADE methods to rate quality/confidence/certainty of evidence. Results 7 RCTs were eligible (n=338 patients). We found DHC reduced death (69–30% in medical vs surgical groups, 39% fewer), and increased the number of patients with mRS of 2–3 (slight to moderate disability: 14–27%, increase of 13%), those with mRS 4 (severe disability: 10–32%, increase of 22%) and those with mRS 5 (very severe disability 7–11%: increase of 4%) (all differences p<0.0001). We judged quality/confidence/certainty of evidence high for death, low for functional outcome mRS 0–3, and moderate for mRS 0–4 (wide CIs and problems in concealment, blinding of outcome assessors and stopping early). Conclusions DHC in SO-MCAi results in large reductions in mortality. Most of those who would otherwise have died are left with severe or very severe disability: for example, inability to walk and a requirement for help with bodily needs, though uncertainty about the proportion with very severe, severe and moderate disability remains (low to moderate quality/confidence/certainty evidence).