Determinants of physical activity in community-dwelling older adults: an umbrella review.

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.

HIV and Black People in Canada: Protocol for a Scoping Review.

BACKGROUND: Race-based health information is necessary to address disproportionate barriers racial communities face and to achieve optimal health outcomes. In Canada, Black people are disproportionately affected by HIV. There is an emerging body of literature on this topic, but a concise summary is lacking. There is a need to collectively and critically analyze research on HIV in the Black population in Canada to identify knowledge gaps and address this disproportionate burden. OBJECTIVE: The aim of this scoping review is to summarize the evidence on HIV and Black people in Canada. The main outcomes of interest are HIV prevalence, access to care, HIV prevention and treatment, the HIV care cascade, and related HIV outcomes. Through this scoping review, we aim to provide a comprehensive overview of the existing literature and highlight topics that need more investigation in future research. METHODS: We will conduct a scoping review of electronic databases using a systematic search strategy for qualitative, quantitative, or mixed methods studies reporting on HIV and Black people in Canada. We will conduct our searches in MEDLINE, Embase, CINAHL, Web of Science, EBSCO, and Google Scholar for literature published between 1985 and 2023. Gray literature, including government reports, dissertations, and other reports, will be included. Search results will be screened, and the full text of relevant literature will be retrieved. The extraction of data will be conducted independently by 2 reviewers. Consensus meetings will be held to resolve conflicts. Our results will be reported according to the PRISMA-ScR (Preferred Reporting Items for the Systematic Reviews and Meta-Analyses Extension for Scoping Reviews). RESULTS: The initial title and abstract review identified 447 articles. These articles will be critically appraised, and relevant information will be extracted. Information from these articles will be compared using charts and tables. Screening will start in November 2023, and we anticipate publishing the scoping review in June 2024. CONCLUSIONS: The findings from this scoping review will help inform policy, practice, and research on HIV and Black people in Canada. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/49066.

Virtual prevention of eating disorders in children, adolescents, and emerging adults: a scoping review.

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.

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.

Help-seeking attitudes and behaviours among youth with eating disorders: a scoping review.

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.

Determinants of physical activity in older adults: an umbrella review protocol.

OBJECTIVE: The aim of this review is to summarize the evidence for determinants of physical activity in older adults. INTRODUCTION: Physical activity is an important predictor of multi-morbidity, falls, and cognitive decline in older adulthood. Understanding what influences older adults' physical activity behavior is an important first step for guiding effective interventions for promoting physical activity in this population. INCLUSION CRITERIA: This umbrella review will include systematic reviews (including scoping reviews) reporting on the relationship between determinants (also referred to as correlates or factors), measured by either self-report or direct measurement, and physical activity in adults ≥60 years. METHODS: A systematic search of six databases will be completed in MEDLINE, Embase, CINAHL, Cochrane Library, PsycINFO, and AgeLine. Two independent reviewers will screen titles, abstracts, and full-text articles, and perform data extraction and quality assessment. Evidence for determinants of physical activity will be synthesized using the socio-ecological model. If possible, evidence will be compared by study design, type of physical activity, outcome measure used, setting, and sex. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020159332.

The COVID-19 pandemic and eating disorders in children, adolescents, and emerging adults: virtual care recommendations from the Canadian consensus panel during COVID-19 and beyond.

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.

Canadian practice guidelines for the treatment of children and adolescents with eating disorders.

OBJECTIVES: Eating disorders are common and serious conditions affecting up to 4% of the population. The mortality rate is high. Despite the seriousness and prevalence of eating disorders in children and adolescents, no Canadian practice guidelines exist to facilitate treatment decisions. This leaves clinicians without any guidance as to which treatment they should use. Our objective was to produce such a guideline. METHODS: Using systematic review, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, and the assembly of a panel of diverse stakeholders from across the country, we developed high quality treatment guidelines that are focused on interventions for children and adolescents with eating disorders. RESULTS: Strong recommendations were supported specifically in favour of Family-Based Treatment, and more generally in terms of least intensive treatment environment. Weak recommendations in favour of Multi-Family Therapy, Cognitive Behavioural Therapy, Adolescent Focused Psychotherapy, adjunctive Yoga and atypical antipsychotics were confirmed. CONCLUSIONS: Several gaps for future work were identified including enhanced research efforts on new primary and adjunctive treatments in order to address severe eating disorders and complex co-morbidities.

A systematic survey identified 36 criteria for assessing effect modification claims in randomized trials or meta-analyses.

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.

Antibiotic Prophylaxis in the Management of Open Fractures: A Systematic Survey of Current Practice and Recommendations.

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.

Evaluating Progression-Free Survival as a Surrogate Outcome for Health-Related Quality of Life in Oncology: A Systematic Review and Quantitative Analysis.

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.

Addition of Ezetimibe to statins for patients at high cardiovascular risk: Systematic review of patient-important outcomes.

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.

Systematic review on costs and resource use of randomized clinical trials shows a lack of transparent and comprehensive data.

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.

Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections.

BACKGROUND: Acute respiratory infections (ARIs) comprise of a large and heterogeneous group of infections including bacterial, viral, and other aetiologies. In recent years, procalcitonin (PCT), a blood marker for bacterial infections, has emerged as a promising tool to improve decisions about antibiotic therapy (PCT-guided antibiotic therapy). Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with ARIs and different settings ranging from primary care settings to emergency departments, hospital wards, and intensive care units. However, the effect of using procalcitonin on clinical outcomes is unclear. This is an update of a Cochrane review and individual participant data meta-analysis first published in 2012 designed to look at the safety of PCT-guided antibiotic stewardship. OBJECTIVES: The aim of this systematic review based on individual participant data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE, and Embase, in February 2017, to identify suitable trials. We also searched ClinicalTrials.gov to identify ongoing trials in April 2017. SELECTION CRITERIA: We included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm (PCT-guided antibiotic stewardship algorithm) or usual care. We excluded trials if they focused exclusively on children or used procalcitonin for a purpose other than to guide initiation and duration of antibiotic treatment. DATA COLLECTION AND ANALYSIS: Two teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days, for which definitions were harmonised among trials. Secondary endpoints were antibiotic use, antibiotic-related side effects, and length of hospital stay. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression adjusted for age, gender, and clinical diagnosis using a fixed-effect model. The different trials were added as random-effects into the model. We conducted sensitivity analyses stratified by clinical setting and type of ARI. We also performed an aggregate data meta-analysis. MAIN RESULTS: From 32 eligible RCTs including 18 new trials for this 2017 update, we obtained individual participant data from 26 trials including 6708 participants, which we included in the main individual participant data meta-analysis. We did not obtain individual participant data for four trials, and two trials did not include people with confirmed ARIs. According to GRADE, the quality of the evidence was high for the outcomes mortality and antibiotic exposure, and quality was moderate for the outcomes treatment failure and antibiotic-related side effects.Primary endpoints: there were 286 deaths in 3336 procalcitonin-guided participants (8.6%) compared to 336 in 3372 controls (10.0%), resulting in a significantly lower mortality associated with procalcitonin-guided therapy (adjusted OR 0.83, 95% CI 0.70 to 0.99, P = 0.037). We could not estimate mortality in primary care trials because only one death was reported in a control group participant. Treatment failure was not significantly lower in procalcitonin-guided participants (23.0% versus 24.9% in the control group, adjusted OR 0.90, 95% CI 0.80 to 1.01, P = 0.068). Results were similar among subgroups by clinical setting and type of respiratory infection, with no evidence for effect modification (P for interaction > 0.05). Secondary endpoints: procalcitonin guidance was associated with a 2.4-day reduction in antibiotic exposure (5.7 versus 8.1 days, 95% CI -2.71 to -2.15, P < 0.001) and lower risk of antibiotic-related side effects (16.3% versus 22.1%, adjusted OR 0.68, 95% CI 0.57 to 0.82, P < 0.001). Length of hospital stay and intensive care unit stay were similar in both groups. A sensitivity aggregate-data analysis based on all 32 eligible trials showed similar results. AUTHORS' CONCLUSIONS: This updated meta-analysis of individual participant data from 12 countries shows that the use of procalcitonin to guide initiation and duration of antibiotic treatment results in lower risks of mortality, lower antibiotic consumption, and lower risk for antibiotic-related side effects. Results were similar for different clinical settings and types of ARIs, thus supporting the use of procalcitonin in the context of antibiotic stewardship in people with ARIs. Future high-quality research is needed to confirm the results in immunosuppressed patients and patients with non-respiratory infections.

Towards the development of a comprehensive framework: Qualitative systematic survey of definitions of clinical research quality.

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.

Premature trial discontinuation often not accurately reflected in registries: comparison of registry records with publications.

BACKGROUND: One quarter of randomized clinical trials (RCTs) are prematurely discontinued and frequently remain unpublished. Trial registries can document whether a trial is ongoing, suspended, discontinued, or completed and therefore represent an important source for trial status information. The accuracy of this information is unclear. OBJECTIVE: To examine the accuracy of completion status and reasons for discontinuation documented in trial registries as compared to corresponding publications of discontinued RCTs and to investigate potential predictors for accurate trial status information in registries. METHODS: We conducted a cross-sectional study comparing information provided in publications (reference standard) to corresponding registry entries. First, we reviewed publications of RCTs providing information on both discontinuation and registration. We identified eligible publications through systematic searches of MEDLINE and EMBASE (2010-2014) and an international cohort of 1,017 RCTs initiated between 2000 and 2003. Second, pairs of investigators independently and in duplicate extracted data from publications and corresponding registry records. Third, for each discontinued RCT, we compared publication information to registry information. We used multivariable regression to examine whether accurate labeling of trials as discontinued (vs. other status) in the registry was associated with recent initiation of RCT, industry sponsorship, multicenter design, or larger sample size. RESULTS: We identified 173 publications of RCTs that were discontinued due to slow recruitment (55%), harm (16%), futility (11%), benefit (5%), other reasons (3%), or multiple reasons (9%). Trials were registered with clinicaltrials.gov (77%), isrctn.com (14%), or other registries (8%). Of the 173 corresponding registry records, 77 (45%) trials were labeled as discontinued and 57 (33%) provided a reason for discontinuation (of which 53, 93%, provided the same reason as in the publication). Labeling of discontinued trials as discontinued (vs. other label) in corresponding trial registry records improved over time (adjusted odds ratio 1.16 per year, confidence interval 1.04-1.30) and was possibly associated with industry sponsorship (2.01, 0.99-4.07) but unlikely with multicenter status (0.81, 0.32-2.04) or sample size (1.07, 0.89-1.29). CONCLUSIONS: Less than half of published discontinued RCTs were accurately labelled as discontinued in corresponding registry records. One-third of registry records provided a reason for discontinuation. Current trial status information in registries should be viewed with caution.

Efficacy and safety of psychostimulants for amphetamine and methamphetamine use disorders: a systematic review and meta-analysis.

BACKGROUND: Amphetamine and methamphetamine use disorders are associated with severe health and social consequences. No pharmacological therapy has been approved for the treatment of these disorders. Psychostimulants can act as maintenance-like therapies for managing substance use among these patients. The aim of this study is to evaluate the literature examining the efficacy and safety of psychostimulant agents for increasing abstinence and treatment retention among patients with amphetamine and methamphetamine use disorders. METHODS: We searched MEDLINE, EMBASE, PsycInfo, Cochrane Central, and CINAHL from inception to August 2016. Selection of studies, data extraction, and risk of bias assessment were conducted independently by two reviewers. We conducted meta-analyses to provide a pooled summary estimate for included trials and report the review according to PRISMA guidelines. RESULTS: We identified and selected 17 studies with 1387 participants. Outcome reporting across trials was inconsistent, and the overall quality of evidence was very low due to high risk of bias and indirectness. A meta-analysis of five trials (642 participants) found no effect of psychostimulants for end-of-study abstinence (odds ratio = 0.97, 95% confidence interval 0.65 to 1.45). Additionally, the pooled estimate from 14 studies (1184 participants) showed no effect of psychostimulants for treatment retention (odds ratio = 1.20, 95% confidence interval = 0.91 to 1.58). The incidence of serious adverse events did not differ between intervention and placebo groups based on qualitative reports from trials. CONCLUSIONS: Quantitative analyses showed no effect of psychostimulants for sustained abstinence or treatment retention. We also identified the need for more rigorous studies in this research area with clinician and patient important outcomes.

Hemicraniectomy versus medical treatment with large MCA infarct: a review and meta-analysis.

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).

Light therapy for non-seasonal depression: systematic review and meta-analysis.

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 (I2=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. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Association between progression-free survival and health-related quality of life in oncology: a systematic review protocol.

INTRODUCTION: There is an increasing number of new oncology drugs being studied, approved and put into clinical practice based on improvement in progression-free survival, when no overall survival benefits exist. In oncology, the association between progression-free survival and health-related quality of life is currently unknown, despite its importance for patients with cancer, and the unverified assumption that longer progression-free survival indicates improved health-related quality of life. Thus far, only 1 study has investigated this association, providing insufficient evidence and inconclusive results. The objective of this study protocol is to provide increased transparency in supporting a systematic summary of the evidence bearing on this association in oncology. METHODS AND ANALYSIS: Using the OVID platform in MEDLINE, Embase and Cochrane databases, we will conduct a systematic review of randomised controlled human trials addressing oncology issues published starting in 2000. A team of reviewers will, in pairs, independently screen and abstract data using standardised, pilot-tested forms. We will employ numerical integration to calculate mean incremental area under the curve between treatment groups in studies for health-related quality of life, along with total related error estimates, and a 95% CI around incremental area. To describe the progression-free survival to health-related quality of life association, we will construct a scatterplot for incremental health-related quality of life versus incremental progression-free survival. To estimate the association, we will use a weighted simple regression approach, comparing mean incremental health-related quality of life with either median incremental progression-free survival time or the progression-free survival HR, in the absence of overall survival benefit. DISCUSSION: Identifying direction and magnitude of association between progression-free survival and health-related quality of life is critically important in interpreting results of oncology trials. Systematic evidence produced from our study will contribute to improvement of patient care and practice of evidence-based medicine in oncology.