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Elaine Beller and colleagues from the PRISMA for Abstracts group provide a reporting guidelines for reporting abstracts of systematic reviews in journals and at conferences.Elaine Beller and colleagues from the PRISMA for Abstracts group provide a reporting guidelines for reporting abstracts of systematic reviews in journals and at conferences.

Paul Glasziou and colleagues discuss methods to guide selection of an intervention from individual trials within a systematic review. Please see later in the article for the Editors' Summary.Paul Glasziou and colleagues discuss methods to guide selection of an intervention from individual trials within a systematic review. Please see later in the article for the Editors' Summary.

Financial ties between health professionals and industry may unduly influence professional judgments and some researchers have suggested that widening disease definitions may be one driver of over-diagnosis, bringing potentially unnecessary labeling and harm. We aimed to identify guidelines in which disease definitions were changed, to assess whether any proposed changes would increase the numbers of individuals considered to have the disease, whether potential harms of expanding disease definitions were investigated, and the extent of members' industry ties. We undertook a cross-sectional study of the most recent publication between 2000 and 2013 from national and international guideline panels making decisions about definitions or diagnostic criteria for common conditions in the United States. We assessed whether proposed changes widened or narrowed disease definitions, rationales offered, mention of potential harms of those changes, and the nature and extent of disclosed ties between members and pharmaceutical or device companies. Of 16 publications on 14 common conditions, ten proposed changes widening and one narrowing definitions. For five, impact was unclear. Widening fell into three categories: creating \"pre-disease\"; lowering diagnostic thresholds; and proposing earlier or different diagnostic methods. Rationales included standardising diagnostic criteria and new evidence about risks for people previously considered to not have the disease. No publication included rigorous assessment of potential harms of proposed changes. Among 14 panels with disclosures, the average proportion of members with industry ties was 75%. Twelve were chaired by people with ties. For members with ties, the median number of companies to which they had ties was seven. Companies with ties to the highest proportions of members were active in the relevant therapeutic area. Limitations arise from reliance on only disclosed ties, and exclusion of conditions too broad to enable analysis of single panel publications. For the common conditions studied, a majority of panels proposed changes to disease definitions that increased the number of individuals considered to have the disease, none reported rigorous assessment of potential harms of that widening, and most had a majority of members disclosing financial ties to pharmaceutical companies. Please see later in the article for the Editors' Summary.

Half the US population uses drugs with anticholinergic properties. Their potential harms may outweigh their benefits. Amitriptyline is among the most frequently prescribed anticholinergic medicinal products, is used for multiple indications, and rated as strongly anticholinergic. Our objective was to explore and quantify (anticholinergic) adverse drug reactions (ADRs) in patients taking amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults and healthy individuals. We searched electronic databases from their inception until 09/2022, and clinical trial registries from their inception until 09/2022. We also performed manual reference searches. Two independent reviewers selected RCTs with ≥100 participants of ≥18 years, that compared amitriptyline (taken orally) versus placebo for all indications. No language restrictions were applied. One reviewer extracted study data, ADRs, and assessed study quality, which two others verified. The primary outcome was frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups. Twenty-three RCTs (mean dosage 5mg to 300mg amitriptyline/day) and 4217 patients (mean age 40.3 years) were included. The most frequently reported anticholinergic ADRs were dry mouth, drowsiness, somnolence, sedation, fatigue, constitutional, and unspecific anticholinergic ADRs. Random-effects meta-analyses showed anticholinergic ADRs had a higher odd's ratio for amitriptyline versus placebo (OR = 7.41; [95% CI, 4.54 to 12.12]). Non-anticholinergic ADRs were as frequent for amitriptyline as placebo. Meta-regression analysis showed anticholinergic ADRs were not dose-dependent. The large OR in our analysis shows that ADRs indicative of anticholinergic activities can be attributed to amitriptyline. The low average age of participants in our study may limit the generalizability of the frequency of anticholinergic ADRs in older patients. A lack of dose-dependency may reflect limited reporting of the daily dosage when the ADRs occurred. The exclusion of small studies (<100 participants) decreased heterogeneity between studies, but may also have reduced our ability to detect rare events. Future studies should focus on older people, as they are more susceptible to anticholinergic ADRs. PROSPERO: CRD42020111970.

For osteoarthritis of the hip, a recent Cochrane review of 10 RCTs of land-based exercise compared with no exercise (of which seven were deemed to have a low risk of bias) showed evidence of benefit.11 High-quality evidence from nine trials (549 participants) showed that, immediately after treatment, exercise reduced pain (SMD -0.38, 95 CI% -0.55 to -0.20), with an absolute reduction of 8 points (95% CI 4 to 11) on a 0-100 scale (a lower score was better). There was also high-quality evidence (nine RCTs involving 521 participants) that exercise improved physical function immediately after treatment (SMD -0.33, 95% CI -0.54 to -0.05), with an absolute decrease of 7 points (95% CI 1 to 12) on a 0-100 scale (a lower score was better). The benefits for pain and physical function were sustained to at least three to six months after the exercise interventions. Only three small studies (183 participants) evaluated the effect of exercise on QoL, with overall low-quality evidence showing no benefit (SMD 0.07, 95% CI -0.23 to 0.36). The well-documented strong placebo effects for self-reported outcomes in osteoarthritis have not been controlled for in most studies of exercise, because participants have not been blinded to group allocation. Therefore, the exact amounts of beneficial effects directly arising from exercise cannot be determined. In a Cochrane review of exercise for low-back pain, 43 RCTs involving patients with chronic low-back pain were included.26 In a meta-analysis of eight RCTs (n = 370), there was mean improvement of pain at earliest follow-up in the exercise group when compared with the control group (10.2 points, 95 CI% 1.3 to 19.1) on a 0-100 pain scale.26 A companion meta-regression study by the same authors found that the effect of exercise was associated with exercise program characteristics, such as supervision, high dose (> 20 h) and individually designed programs. The authors estimated that an exercise program incorporating the most effective intervention characteristics would provide a larger effect size on pain of 18.1 points (95% CI 11.1 to 25.0) and an effect on function of 5.5 points (95% CI 0.5 to 10.5) on a 0-100 function scale.25 These effects are modest, although they are similar in size to that provided by other treatments. For example, a Cochrane review of nonsteroidal anti-inflammatory drugs reported an improvement in pain of 12.4 points (95% CI 9.3 to 15.5).27 For patients with acute low-back pain, there was no significant difference between exercise groups and control groups for pain and function at earliest follow-up (three RCTs, n = 491). The Cochrane review was confined to pain and function outcomes and did not provide information on other outcomes, such as QoL, work status or prevention of future recurrence. This Cochrane review also did not use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach (available at www.gradeworkinggroup.org) to describe the overall quality of the evidence. A comprehensive meta-analysis of exercise efficacy for glycemic control in participants with type 2 diabetes that included 47 RCTs (8538 patients)17 found that structured, supervised exercise training of at least 12 weeks duration (23 RCTs involving aerobic and/or resistance training) was associated with a decline in glycosylated hemoglobin (HbA1c) level (-0.67%, 95% CI -0.84% to -0.49%) compared with participants in the control group.17 Similar benefits, when compared with the control groups, were also found for aerobic exercise (-0.73%, 95% CI -1.06% to -0.40%), resistance training (-0.57%, 95% CI -1.14% to -0.01%), and combined aerobic and resistance exercise (-0.51%, 95% CI -0.79% to -0.23%). Exercise duration of greater than 150 minutes per week was associated with a greater reduction in HbA1c level (weighted mean difference [WMD] -0.89%, 95% CI -1.26% to -0.51%) compared with durations of 150 minutes or less per week (WMD -0.36%, 95% CI -0.50% to -0.23%). Physical activity advice alone was not effective (-0.16%, 95% CI -0.50% to 0.18%). This review did not use the GRADE approach to describe the overall quality of the evidence. The overall effect of structured exercise on HbA1c level (-0.67%, 95% CI -0.84 to -0.49) was similar to the effect of adding metformin to insulin treatment (-0.60%, 95% CI -0.30% to -0.91%) that was reported in a meta-analysis of 35 RCTs involving patients with diabetes.38

To study the statistical power of randomized clinical trials and examine developments over time. We analyzed the statistical power in 136,212 clinical trials between 1975 and 2014 extracted from meta-analyses from the Cochrane database of systematic reviews. We determined study power to detect standardized effect sizes, where power was based on the meta-analyzed effect size. Average power, effect size, and temporal patterns were examined for all meta-analyses and a subset of significant meta-analyses. The number of trials with power ≥80% was low (7%) but increased over time: from 5% in 1975–1979 to 9% in 2010–2014. In significant meta-analyses, the proportion of trials with sufficient power increased from 9% to 15% in these years (median power increased from 16% to 23%). This increase was mainly due to increasing sample sizes, while effect sizes remained stable with a median Cohen's h of 0.09 (interquartile range 0.04–0.22) and a median Cohen's d of 0.20 (0.11–0.40). This study demonstrates that sufficient power in clinical trials is still problematic, although the situation is slowly improving. Our data encourage further efforts to increase statistical power in clinical trials to guarantee rigorous and reproducible evidence-based medicine.

Lack of good research is a pandemic tragedy

Abstract Objective: To improve the accuracy and completeness of reporting of studies of diagnostic accuracy, to allow readers to assess the potential for bias in a study, and to evaluate a study's generalisability. Methods: The Standards for Reporting of Diagnostic Accuracy (STARD) steering committee searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies and extracted potential items into an extensive list. Researchers, editors, and members of professional organisations shortened this list during a two day consensus meeting, with the goal of developing a checklist and a generic flow diagram for studies of diagnostic accuracy. Results: The search for published guidelines about diagnostic research yielded 33 previously published checklists, from which we extracted a list of 75 potential items. At the consensus meeting, participants shortened the list to a 25 item checklist, by using evidence, whenever available. A prototype of a flow diagram provides information about the method of patient recruitment, the order of test execution, and the numbers of patients undergoing the test under evaluation and the reference standard, or both. Conclusions: Evaluation of research depends on complete and accurate reporting. If medical journals adopt the STARD checklist and flow diagram, the quality of reporting of studies of diagnostic accuracy should improve to the advantage of clinicians, researchers, reviewers, journals, and the public. The Standards for Reporting of Diagnostic Accuracy (STARD) steering group aims to improve the accuracy and completeness of reporting of studies of diagnostic accuracy. The group describes and explains the development of a checklist and flow diagram for authors of reports

Background Chronic disease management (CDM) through sustained knowledge translation (KT) interventions ensures long-term, high-quality care. We assessed implementation of KT interventions for supporting CDM and their efficacy when sustained in older adults. Methods Design: Systematic review with meta-analysis engaging 17 knowledge users using integrated KT. Eligibility criteria: Randomized controlled trials (RCTs) including adults (> 65 years old) with chronic disease(s), their caregivers, health and/or policy-decision makers receiving a KT intervention to carry out a CDM intervention for at least 12 months (versus other KT interventions or usual care). Information sources: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from each database’s inception to March 2020. Outcome measures: Sustainability, fidelity, adherence of KT interventions for CDM practice, quality of life (QOL) and quality of care (QOC). Data extraction, risk of bias (ROB) assessment: We screened, abstracted and appraised articles (Effective Practice and Organisation of Care ROB tool) independently and in duplicate. Data synthesis: We performed both random-effects and fixed-effect meta-analyses and estimated mean differences (MDs) for continuous and odds ratios (ORs) for dichotomous data. Results We included 158 RCTs (973,074 participants [961,745 patients, 5540 caregivers, 5789 providers]) and 39 companion reports comprising 329 KT interventions, involving patients (43.2%), healthcare providers (20.7%) or both (10.9%). We identified 16 studies described as assessing sustainability in 8.1% interventions, 67 studies as assessing adherence in 35.6% interventions and 20 studies as assessing fidelity in 8.7% of the interventions. Most meta-analyses suggested that KT interventions improved QOL, but imprecisely (36 item Short-Form mental [SF-36 mental]: MD 1.11, 95% confidence interval [CI] [− 1.25, 3.47], 14 RCTs, 5876 participants, I 2  = 96%; European QOL-5 dimensions: MD 0.01, 95% CI [− 0.01, 0.02], 15 RCTs, 6628 participants, I 2  = 25%; St George’s Respiratory Questionnaire: MD − 2.12, 95% CI [− 3.72, − 0.51] 44 12 RCTs, 2893 participants, I 2  = 44%). KT interventions improved QOC (OR 1.55, 95% CI [1.29, 1.85], 12 RCTS, 5271 participants, I 2  = 21%). Conclusions KT intervention sustainability was infrequently defined and assessed. Sustained KT interventions have the potential to improve QOL and QOC in older adults with CDM. However, their overall efficacy remains uncertain and it varies by effect modifiers, including intervention type, chronic disease number, comorbidities, and participant age. Systematic review registration PROSPERO CRD42018084810.