Exercise and aerobic capacity in individuals with spinal cord injury: A systematic review with meta-analysis and meta-regression.

BACKGROUND: A low level of cardiorespiratory fitness [CRF; defined as peak oxygen uptake ([Formula: see text]O2peak) or peak power output (PPO)] is a widely reported consequence of spinal cord injury (SCI) and a major risk factor associated with chronic disease. However, CRF can be modified by exercise. This systematic review with meta-analysis and meta-regression aimed to assess whether certain SCI characteristics and/or specific exercise considerations are moderators of changes in CRF. METHODS AND FINDINGS: Databases (MEDLINE, EMBASE, CENTRAL, and Web of Science) were searched from inception to March 2023. A primary meta-analysis was conducted including randomised controlled trials (RCTs; exercise interventions lasting >2 weeks relative to control groups). A secondary meta-analysis pooled independent exercise interventions >2 weeks from longitudinal pre-post and RCT studies to explore whether subgroup differences in injury characteristics and/or exercise intervention parameters explained CRF changes. Further analyses included cohort, cross-sectional, and observational study designs. Outcome measures of interest were absolute (A[Formula: see text]O2peak) or relative [Formula: see text]O2peak (R[Formula: see text]O2peak), and/or PPO. Bias/quality was assessed via The Cochrane Risk of Bias 2 and the National Institute of Health Quality Assessment Tools. Certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Random effects models were used in all meta-analyses and meta-regressions. Of 21,020 identified records, 120 studies comprising 29 RCTs, 67 pre-post studies, 11 cohort, 7 cross-sectional, and 6 observational studies were included. The primary meta-analysis revealed significant improvements in A[Formula: see text]O2peak [0.16 (0.07, 0.25) L/min], R[Formula: see text]O2peak [2.9 (1.8, 3.9) mL/kg/min], and PPO [9 (5, 14) W] with exercise, relative to controls (p < 0.001). Ninety-six studies (117 independent exercise interventions comprising 1,331 adults with SCI) were included in the secondary, pooled meta-analysis which demonstrated significant increases in A[Formula: see text]O2peak [0.22 (0.17, 0.26) L/min], R[Formula: see text]O2peak [2.8 (2.2, 3.3) mL/kg/min], and PPO [11 (9, 13) W] (p < 0.001) following exercise interventions. There were subgroup differences for R[Formula: see text]O2peak based on exercise modality (p = 0.002) and intervention length (p = 0.01), but there were no differences for A[Formula: see text]O2peak. There were subgroup differences (p ≤ 0.018) for PPO based on time since injury, neurological level of injury, exercise modality, and frequency. The meta-regression found that studies with a higher mean age of participants were associated with smaller changes in A[Formula: see text]O2peak and R[Formula: see text]O2peak (p < 0.10). GRADE indicated a moderate level of certainty in the estimated effect for R[Formula: see text]O2peak, but low levels for A[Formula: see text]O2peak and PPO. This review may be limited by the small number of RCTs, which prevented a subgroup analysis within this specific study design. CONCLUSIONS: Our primary meta-analysis confirms that performing exercise >2 weeks results in significant improvements to A[Formula: see text]O2peak, R[Formula: see text]O2peak, and PPO in individuals with SCI. The pooled meta-analysis subgroup comparisons identified that exercise interventions lasting up to 12 weeks yield the greatest change in R[Formula: see text]O2peak. Upper-body aerobic exercise and resistance training also appear the most effective at improving R[Formula: see text]O2peak and PPO. Furthermore, acutely injured, individuals with paraplegia, exercising for ≥3 sessions/week will likely experience the greatest change in PPO. Ageing seemingly diminishes the adaptive CRF responses to exercise training in individuals with SCI. REGISTRATION: PROSPERO: CRD42018104342.

Rapid antigen-based and rapid molecular tests for the detection of SARS-CoV-2: a rapid review with network meta-analysis of diagnostic test accuracy studies.

BACKGROUND: The global spread of COVID-19 created an explosion in rapid tests with results in < 1 hour, but their relative performance characteristics are not fully understood yet. Our aim was to determine the most sensitive and specific rapid test for the diagnosis of SARS-CoV-2. METHODS: Design: Rapid review and diagnostic test accuracy network meta-analysis (DTA-NMA). ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) and observational studies assessing rapid antigen and/or rapid molecular test(s) to detect SARS-CoV-2 in participants of any age, suspected or not with SARS-CoV-2 infection. INFORMATION SOURCES: Embase, MEDLINE, and Cochrane Central Register of Controlled Trials, up to September 12, 2021. OUTCOME MEASURES: Sensitivity and specificity of rapid antigen and molecular tests suitable for detecting SARS-CoV-2. Data extraction and risk of bias assessment: Screening of literature search results was conducted by one reviewer; data abstraction was completed by one reviewer and independently verified by a second reviewer. Risk of bias was not assessed in the included studies. DATA SYNTHESIS: Random-effects meta-analysis and DTA-NMA. RESULTS: We included 93 studies (reported in 88 articles) relating to 36 rapid antigen tests in 104,961 participants and 23 rapid molecular tests in 10,449 participants. Overall, rapid antigen tests had a sensitivity of 0.75 (95% confidence interval 0.70-0.79) and specificity of 0.99 (0.98-0.99). Rapid antigen test sensitivity was higher when nasal or combined samples (e.g., combinations of nose, throat, mouth, or saliva samples) were used, but lower when nasopharyngeal samples were used, and in those classified as asymptomatic at the time of testing. Rapid molecular tests may result in fewer false negatives than rapid antigen tests (sensitivity: 0.93, 0.88-0.96; specificity: 0.98, 0.97-0.99). The tests with the highest sensitivity and specificity estimates were the Xpert Xpress rapid molecular test by Cepheid (sensitivity: 0.99, 0.83-1.00; specificity: 0.97, 0.69-1.00) among the 23 commercial rapid molecular tests and the COVID-VIRO test by AAZ-LMB (sensitivity: 0.93, 0.48-0.99; specificity: 0.98, 0.44-1.00) among the 36 rapid antigen tests we examined. CONCLUSIONS: Rapid molecular tests were associated with both high sensitivity and specificity, while rapid antigen tests were mainly associated with high specificity, according to the minimum performance requirements by WHO and Health Canada. Our rapid review was limited to English, peer-reviewed published results of commercial tests, and study risk of bias was not assessed. A full systematic review is required. REVIEW REGISTRATION: PROSPERO CRD42021289712.

One-Third of Systematic Reviews in Rehabilitation Applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) System to Evaluate Certainty of Evidence: A Meta-Research Study.

OBJECTIVE: To determine how many systematic reviews (SRs) of the literature in rehabilitation assess the certainty of evidence (CoE) and how many apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to do this. DATA SOURCES: For this meta-research study, we searched PubMed and Cochrane Database of Systematic Reviews databases for SRs on rehabilitation published in 2020. STUDY SELECTION AND DATA EXTRACTION: Two reviewers independently selected the SRs and extracted the data. Reporting characteristics and appropriate use of the GRADE system were assessed. DATA SYNTHESIS: The search retrieved 827 records: 29% (239/827) SRs evaluated CoE, 68% (163/239) of which applied the GRADE system. GRADE was used by SRs of randomized controlled trials (RCTs, 88%; 144/163), non-randomized intervention studies (NRIS, 2%; 3/163), and both RCT and NRIS (10%; 16/163). In the latter case, a separate GRADE assessment according to the study design was not provided in 75% (12/16). The reasons for GRADE judgment were reported in 82% (134/163) of SRs. CONCLUSIONS: One-third of SRs in rehabilitation assessed CoE with the GRADE system. GRADE assessment was presented transparently by most SRs. Journal editors and funders should encourage the uptake of the GRADE system when considering SRs in rehabilitation for publication. The authors should pre-define GRADE assessment in a registered and/or published protocol.

Managing overlap of primary study results across systematic reviews: practical considerations for authors of overviews of reviews.

BACKGROUND: Overviews often identify and synthesise a large number of systematic reviews on the same topic, which is likely to lead to overlap (i.e. duplication) in primary studies across the reviews. Using a primary study result multiple times in the same analysis overstates its sample size and number of events, falsely leading to greater precision in the analysis. This paper aims to: (a) describe types of overlapping data that arise from the same primary studies reported across multiple reviews, (b) describe methods to identify and explain overlap of primary study data, and (c) present six case studies illustrating different approaches to manage overlap. METHODS: We first updated the search in PubMed for methods from the MOoR framework relating to overlap of primary studies. One author screened the studies titles and abstracts, and any full-text articles retrieved, extracted methods data relating to overlap of primary studies and mapped it to the overlap methods from the MOoR framework. We also describe six case studies as examples of overviews that use specific overlap methods across the steps in the conduct of an overview. For each case study, we discuss potential methodological implications in terms of limitations, efficiency, usability, and resource use. RESULTS: Nine methods studies were found and mapped to the methods identified by the MOoR framework to address overlap. Overlap methods were mapped across four steps in the conduct of an overview - the eligibility criteria step, the data extraction step, the assessment of risk of bias step, and the synthesis step. Our overview case studies used multiple methods to reduce overlap at different steps in the conduct of an overview. CONCLUSIONS: Our study underlines that there is currently no standard methodological approach to deal with overlap in primary studies across reviews. The level of complexity when dealing with overlap can vary depending on the yield, trends and patterns of the included literature and the scope of the overview question. Choosing a method might be dependent on the number of included reviews and their primary studies. Gaps in evaluation of methods to address overlap were found and further investigation in this area is needed.

Database combinations to retrieve systematic reviews in overviews of reviews: a methodological study.

BACKGROUND: When conducting an Overviews of Reviews on health-related topics, it is unclear which combination of bibliographic databases authors should use for searching for SRs. Our goal was to determine which databases included the most systematic reviews and identify an optimal database combination for searching systematic reviews. METHODS: A set of 86 Overviews of Reviews with 1219 included systematic reviews was extracted from a previous study. Inclusion of the systematic reviews was assessed in MEDLINE, CINAHL, Embase, Epistemonikos, PsycINFO, and TRIP. The mean inclusion rate (% of included systematic reviews) and corresponding 95% confidence interval were calculated for each database individually, as well as for combinations of MEDLINE with each other database and reference checking. RESULTS: Inclusion of systematic reviews was higher in MEDLINE than in any other single database (mean inclusion rate 89.7%; 95% confidence interval [89.0-90.3%]). Combined with reference checking, this value increased to 93.7% [93.2-94.2%]. The best combination of two databases plus reference checking consisted of MEDLINE and Epistemonikos (99.2% [99.0-99.3%]). Stratification by Health Technology Assessment reports (97.7% [96.5-98.9%]) vs. Cochrane Overviews (100.0%) vs. non-Cochrane Overviews (99.3% [99.1-99.4%]) showed that inclusion was only slightly lower for Health Technology Assessment reports. However, MEDLINE, Epistemonikos, and reference checking remained the best combination. Among the 10/1219 systematic reviews not identified by this combination, five were published as websites rather than journals, two were included in CINAHL and Embase, and one was included in the database ERIC. CONCLUSIONS: MEDLINE and Epistemonikos, complemented by reference checking of included studies, is the best database combination to identify systematic reviews on health-related topics.

Interventions for escalation of therapy for acute exacerbations of asthma in children: an overview of Cochrane Reviews.

BACKGROUND: Asthma is an illness that commonly affects adults and children, and it serves as a common reason for children to attend emergency departments. An asthma exacerbation is characterised by acute or subacute worsening of shortness of breath, cough, wheezing, and chest tightness and may be triggered by viral respiratory infection, poor compliance with usual medication, a change in the weather, or exposure to allergens or irritants. Most children with asthma have mild or moderate exacerbations and respond well to first-line therapy (inhaled short-acting beta-agonists and systemic corticosteroids). However, the best treatment for the small proportion of seriously ill children who do not respond to first-line therapy is not well understood. Currently, a large number of treatment options are available and there is wide variation in management. OBJECTIVES: Main objective - To summarise Cochrane Reviews with or without meta-analyses of randomised controlled trials on the efficacy and safety of second-line treatment for children with acute exacerbations of asthma (i.e. after first-line treatments, titrated oxygen delivery, and administration of intermittent inhaled short-acting beta2-agonists and oral corticosteroids have been tried and have failed) Secondary objectives - To identify gaps in the current evidence base that will inform recommendations for future research and subsequent Cochrane Reviews - To categorise information on reported outcome measures used in trials of escalation of treatment for acute exacerbations of asthma in children, and to make recommendations for development and reporting of standard outcomes in future trials and reviews - To identify relevant randomised controlled trials that have been published since the date of publication of each included review METHODS: We included Cochrane Reviews assessing interventions for children with acute exacerbations of asthma. We searched the Cochrane Database of Systematic Reviews. The search is current to 28 December 2019. We also identified trials that were potentially eligible for, but were not currently included in, published reviews. We assessed the quality of included reviews using the ROBIS criteria (tool used to assess risk of bias in systematic reviews). We presented an evidence synthesis of data from reviews alongside an evidence map of clinical trials. Primary outcomes were length of stay, hospital admission, intensive care unit admission, and adverse effects. We summarised all findings in the text and reported data for each outcome in 'Additional tables'. MAIN RESULTS: We identified 17 potentially eligible Cochrane Reviews but extracted data from, and rated the quality of, 13 reviews that reported results for children alone. We excluded four reviews as one did not include any randomised controlled trials (RCTs), one did not provide subgroup data for children, and the last two had been updated and replaced by subsequent reviews. The 13 reviews included 67 trials; the number of trials in each review ranged from a single trial up to 27 trials. The vast majority of comparisons included between one and three trials, involving fewer than 100 participants. The total number of participants included in reviews ranged from 40 to 2630. All studies included children; 16 (24%) included children younger than two years of age. Most of the reviews reported search dates older than four years. We have summarised the published evidence as outlined in Cochrane Reviews. Key findings, in terms of our primary outcomes, are that (1) intravenous magnesium sulfate was the only intervention shown to reduce hospital length of stay (high-certainty evidence); (2) no evidence suggested that any intervention reduced the risk of intensive care admission (low- to very low-certainty evidence); (3) the risk of hospital admission was reduced by the addition of inhaled anticholinergic agents to inhaled beta2-agonists (moderate-certainty evidence), the use of intravenous magnesium sulfate (high-certainty evidence), and the use of inhaled heliox (low-certainty evidence); (4) the addition of inhaled magnesium sulfate to usual bronchodilator therapy appears to reduce serious adverse events during hospital admission (moderate-certainty evidence); (5) aminophylline increased vomiting compared to placebo (moderate-certainty evidence) and increased nausea and nausea/vomiting compared to intravenous beta2-agonists (low-certainty evidence); and (6) the addition of anticholinergic therapy to short-acting beta2-agonists appeared to reduce the risk of nausea (high-certainty evidence) and tremor (moderate-certainty evidence) but not vomiting (low-certainty evidence). We considered 4 of the 13 reviews to be at high risk of bias based on the ROBIS framework. In all cases, this was due to concerns regarding identification and selection of studies. The certainty of evidence varied widely (by review and also by outcome) and ranged from very low to high. AUTHORS' CONCLUSIONS: This overview provides the most up-to-date evidence on interventions for escalation of therapy for acute exacerbations of asthma in children from Cochrane Reviews of randomised controlled trials. A vast majority of comparisons involved between one and three trials and fewer than 100 participants, making it difficult to assess the balance between benefits and potential harms. Due to the lack of comparative studies between various treatment options, we are unable to make firm practice recommendations. Intravenous magnesium sulfate appears to reduce both hospital length of stay and the risk of hospital admission. Hospital admission is also reduced with the addition of inhaled anticholinergic agents to inhaled beta2-agonists. However, further research is required to determine which patients are most likely to benefit from these therapies. Due to the relatively rare incidence of acute severe paediatric asthma, multi-centre research will be required to generate high-quality evidence. A number of existing Cochrane Reviews should be updated, and we recommend that a new review be conducted on the use of high-flow nasal oxygen therapy. Important priorities include development of an internationally agreed core outcome set for future trials in acute severe asthma exacerbations and determination of clinically important differences in these outcomes, which can then inform adequately powered future trials.

Preoperative Use of Oral Beta-Adrenergic Blocking Agents and the Incidence of New-Onset Atrial Fibrillation After Cardiac Surgery. A Systematic Review and Meta-Analysis.

BACKGROUND: Current epidemiological data suggests that postoperative atrial fibrillation or atrial flutter (POAF) causes significant morbidity and mortality after cardiac surgery. The literature for prophylactic management of POAF is limited, resulting in the lack of clear guidelines on management recommendations. AIM: To examine the efficacy of prophylactic rate control agents in reducing the incidence of new-onset POAF in patients undergoing elective cardiac surgery. METHODS: Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Medline were systematically searched for blinded randomised controlled studies (RCT) evaluating adults with no history of atrial fibrillation randomised to a pharmacological agent (either beta blocker, calcium channel blocker or digoxin), compared to placebo. Utilising Cochrane guidance, three reviewers screened, extracted and the quality of the evidence was assessed. We used a random effects meta-analysis to compare a rate-control agent with placebo. RESULTS: Five RCTs (688 subjects, mean age 61±8.9, 69% male) were included. Beta blocker administration prior to elective cardiac surgery significantly reduced the incidence of POAF (OR 0.43, 95%Cl [0.30-0.61], I2=0%) without significant impact on ischaemic stroke (OR 0.49, 95%Cl [0.10-2.44], I2=0%), non-fatal myocardial infarction (OR 0.76, 95%Cl [0.08-7.44], I2=0%), overall mortality (OR 0.83, 95%Cl [0.19-3.66], I2=0%), or length of stay (mean -0.96days 95%Cl [-1.49 to -0.42], I2=0%). An increased rate of bradycardic episodes was observed (OR 3.53, 95%Cl [1.22-10.23], I2=0%). CONCLUSIONS: This review suggests that selective administration of prophylactic oral beta blockers prior to elective cardiac surgery is safe and may reduce the incidence of POAF.

Methodological review of NMA bias concepts provides groundwork for the development of a list of concepts for potential inclusion in a new risk of bias tool for network meta-analysis (RoB NMA Tool).

INTRODUCTION: Network meta-analyses (NMAs) have gained popularity and grown in number due to their ability to provide estimates of the comparative effectiveness of multiple treatments for the same condition. The aim of this study is to conduct a methodological review to compile a preliminary list of concepts related to bias in NMAs. METHODS AND ANALYSIS: We included papers that present items related to bias, reporting or methodological quality, papers assessing the quality of NMAs, or method papers. We searched MEDLINE, the Cochrane Library and unpublished literature (up to July 2020). We extracted items related to bias in NMAs. An item was excluded if it related to general systematic review quality or bias and was included in currently available tools such as ROBIS or AMSTAR 2. We reworded items, typically structured as questions, into concepts (i.e. general notions). RESULTS: One hundred eighty-one articles were assessed in full text and 58 were included. Of these articles, 12 were tools, checklists or journal standards; 13 were guidance documents for NMAs; 27 were studies related to bias or NMA methods; and 6 were papers assessing the quality of NMAs. These studies yielded 99 items of which the majority related to general systematic review quality and biases and were therefore excluded. The 22 items we included were reworded into concepts specific to bias in NMAs. CONCLUSIONS: A list of 22 concepts was included. This list is not intended to be used to assess biases in NMAs, but to inform the development of items to be included in our tool.

HIGHLIGHTS: • Our research aimed to develop a preliminary list of concepts related to bias with the goal of developing the first tool for assessing the risk of bias in the results and conclusions of a network meta-analysis (NMA).• We followed the methodology proposed by Whiting (2017) and Sanderson (2007) for creating systematically developed lists of quality items, as a first step in the development of a risk of bias tool for network meta-analysis (RoB NMA Tool).• We included items related to biases in NMAs and excluded items that are equally applicable to all systematic reviews as they are covered by other tools (e.g. ROBIS, AMSTAR 2).• Fifty-seven studies were included generating 99 items, which when screened, yielded 22 included items. These items were then reworded into concepts in preparation for a Delphi process for further vetting by external experts.• A limitation of our study is the challenge in retrieving methods studies as methods collections are not regularly updated.

A systematic survey of 200 systematic reviews with network meta-analysis (published 2020-2021) reveals that few reviews report structured evidence summaries.

OBJECTIVES: To map whether and how systematic reviews (SRs) with network meta-analysis (NMA) use presentation formats to report (a) structured evidence summaries - here defined as reporting of effects estimates in absolute effects with certainty ratings and with a method to rate interventions across one or more outcome(s) - and (b) NMA results in general. STUDY DESIGN AND SETTING: We conducted a systematic survey, searching MEDLINE (Ovid) for SRs with NMA published between January 1, 2020, and December 31, 2021. We planned to include a random sample of publications, with predefined mechanisms in place for saturation, and included SRs that met prespecified quality criteria and extracted data on presentation formats that reported: (a) estimates of effects, (b) certainty of the evidence, or (c) rating of interventions. RESULTS: The 200 eligible SRs, from 158 unique Journals, utilized 1133 presentation formats. We found structured evidence summaries in 10 publications (5.0%), with 3 (1.5%) reporting structured evidence summaries across all outcomes, including benefits and harms. Sixteen of the 133 SRs (11.7%) reporting dichotomous outcomes included estimates of absolute effects. Seventy-six SRs (38.0%) reported both benefits and harms and 26 SRs (13.0%) reported certainty ratings in presentation formats, 20 (76.9%) used Grading of Recommendations Assessment, Development and Evaluation and 6 (23.1%) used Confidence In Network Meta-analysis. Surface Under the Cumulative Ranking Curve was the most common method to rate interventions (69 SRs, 34.5%). NMA results were most often reported using forest plots (108 SRs, 54.0%) and league tables (93 SRs, 46.5%). CONCLUSION: Most SRs with NMA do not report structured evidence summaries and only rarely do such summaries include reporting of both benefits and harms; those that do offer effective user-friendly communication and provide models for optimal NMA presentation practice.

Only half of the authors of overviews of exercise-related interventions use some strategy to manage overlapping primary studies-a metaresearch study.

OBJECTIVES: The conduct of systematic reviews (SRs) and overviews share several similarities. However, because the unit of analysis for overviews is the SRs, there are some unique challenges. One of the most critical issues to manage when conducting an overview is the overlap of data across the primary studies included in the SRs. This metaresearch study aimed to describe the frequency of strategies to manage the overlap in overviews of exercise-related interventions. STUDY DESIGN AND SETTING: A systematic search in MEDLINE (Ovid), Embase (Ovid), Cochrane Library, Epistemonikos, and other sources was conducted from inception to June 2022. We included overviews of SRs that considered primary studies and evaluated the effectiveness of exercise-related interventions for any health condition. The overviews were screened by two authors independently, and the extraction was performed by one author and checked by a second. We found 353 overviews published between 2005 and 2022 that met the inclusion criteria. RESULTS: One hundred and sixty-four overviews (46%) used at least one strategy to visualize, quantify, or resolve overlap, with a matrix (32/164; 20%), absolute frequency (34/164; 21%), and authors' algorithms (24/164; 15%) being the most used methods, respectively. From 2016 onwards, there has been a trend toward increasing the use of some strategies to manage overlap. Of the 108 overviews that used some strategy to resolve the overlap, ie, avoiding double or multiple counting of primary study data, 79 (73%) succeeded. In overviews where no strategies to manage overlap were reported (n = 189/353; 54%), 16 overview authors (8%) recognized this as a study limitation. CONCLUSION: Although there is a trend toward increasing its use, only half of the authors of the overviews of exercise-related interventions used a strategy to visualize, quantify, or resolve overlap in the primary studies' data. In the future, authors should report such strategies to communicate more valid results.

Exploring decision-makers' challenges and strategies when selecting multiple systematic reviews: insights for AI decision support tools in healthcare.

BACKGROUND: Systematic reviews (SRs) are being published at an accelerated rate. Decision-makers may struggle with comparing and choosing between multiple SRs on the same topic. We aimed to understand how healthcare decision-makers (eg, practitioners, policymakers, researchers) use SRs to inform decision-making and to explore the potential role of a proposed artificial intelligence (AI) tool to assist in critical appraisal and choosing among SRs. METHODS: We developed a survey with 21 open and closed questions. We followed a knowledge translation plan to disseminate the survey through social media and professional networks. RESULTS: Our survey response rate was lower than expected (7.9% of distributed emails). Of the 684 respondents, 58.2% identified as researchers, 37.1% as practitioners, 19.2% as students and 13.5% as policymakers. Respondents frequently sought out SRs (97.1%) as a source of evidence to inform decision-making. They frequently (97.9%) found more than one SR on a given topic of interest to them. Just over half (50.8%) struggled to choose the most trustworthy SR among multiple. These difficulties related to lack of time (55.2%), or difficulties comparing due to varying methodological quality of SRs (54.2%), differences in results and conclusions (49.7%) or variation in the included studies (44.6%). Respondents compared SRs based on the relevance to their question of interest, methodological quality, and recency of the SR search. Most respondents (87.0%) were interested in an AI tool to help appraise and compare SRs. CONCLUSIONS: Given the identified barriers of using SR evidence, an AI tool to facilitate comparison of the relevance of SRs, the search and methodological quality, could help users efficiently choose among SRs and make healthcare decisions.

Methods proposed for monitoring the implementation of evidence-based research: a cross-sectional study.

OBJECTIVES: Evidence-based research (EBR) is the systematic and transparent use of prior research to inform a new study so that it answers questions that matter in a valid, efficient, and accessible manner. This study surveyed experts about existing (e.g., citation analysis) and new methods for monitoring EBR and collected ideas about implementing these methods. STUDY DESIGN AND SETTING: We conducted a cross-sectional study via an online survey between November 2022 and March 2023. Participants were experts from the fields of evidence synthesis and research methodology in health research. Open-ended questions were coded by recurring themes; descriptive statistics were used for quantitative questions. RESULTS: Twenty-eight expert participants suggested that citation analysis should be supplemented with content evaluation (not just what is cited but also in which context), content expert involvement, and assessment of the quality of cited systematic reviews. They also suggested that citation analysis could be facilitated with automation tools. They emphasized that EBR monitoring should be conducted by ethics committees and funding bodies before the research starts. Challenges identified for EBR implementation monitoring were resource constraints and clarity on responsibility for EBR monitoring. CONCLUSION: Ideas proposed in this study for monitoring the implementation of EBR can be used to refine methods and define responsibility but should be further explored in terms of feasibility and acceptability. Different methods may be needed to determine if the use of EBR is improving over time.

Surgery and risk for multiple sclerosis: a systematic review and meta-analysis of case-control studies.

BACKGROUND: Although the precise etiology of multiple sclerosis is largely unknown, there is some speculation that a prior history of surgery may be associated with the subsequent risk for developing the disease. Therefore, we aimed to examine surgery as a risk factor for the diagnosis of multiple sclerosis. METHODS: We searched for observational studies that evaluated the risk for developing multiple sclerosis after surgery that occurred in childhood (≤ 20 years of age) or "premorbid" (> 20 years of age). We specifically included surgeries classified as: tonsillectomy, appendectomy, adenoidectomy, or "surgery". We performed a systematic review and meta-analyses and calculated odds ratios (OR) and their 95% confidence intervals (CIs) using a random effects model. RESULTS: We identified 33 case-control studies, involving 27,373 multiple sclerosis cases and 211,756 controls. There was a statistically significant association between tonsillectomy (OR = 1.32, 95% CI 1.08-1.61; 12 studies, I(2) = 44%) and appendectomy (OR = 1.16, 95% CI 1.01-1.34; 7 studies, I(2) = 0%) in individual's ≤ 20 years of age and the subsequent risk for developing multiple sclerosis. There was no statistically significant association between risk for multiple sclerosis and tonsillectomy occurring after age 20 (OR = 1.20, 95% CI 0.94-1.53; 9 studies, I(2) = 32%), in those with appendectomy at > 20 years (OR = 1.26, 95% CI 0.92-1.72; 5 studies, I(2) = 46%), and in those with adenoidectomy at ≤ 20 years of age (OR = 1.06, 95% CI 0.68-1.68; 3 studies, I(2) = 35%). The combined OR of 15 studies (N = 2,380) looking at "surgery" before multiple sclerosis diagnosis was not statistically significant (OR = 1.19, 95% CI 0.83-1.70; I(2) = 71%). CONCLUSIONS: We found a small but statistically significant and clinically important increased risk for developing multiple sclerosis, in those with tonsillectomy and appendectomy at ≤ 20 years of age. There was no convincing evidence to support the association of other surgeries and the risk for multiple sclerosis. Well-designed prospective etiological studies, pertaining to the risk for developing multiple sclerosis, ought to be conducted and should include the examination of various surgeries as risk factors.

Strategies used to manage overlap of primary study data by exercise-related overviews: protocol for a systematic methodological review.

INTRODUCTION: One of the most conflicting methodological issues when conducting an overview is the overlap of primary studies across systematic reviews (SRs). Overlap in the pooled effect estimates across SRs may lead to overly precise effect estimates in the overview. SRs that focus on exercise-related interventions are often included in overviews aimed at grouping and determining the effectiveness of various interventions for managing specific health conditions. The aim of this systematic methodological review is to describe the strategies used by authors of overviews focusing on exercise-related interventions to manage the overlap of primary studies. METHODS AND ANALYSIS: A comprehensive search strategy has been developed for different databases and their platforms. The databases to be consulted will be MEDLINE (Ovid), Embase (Ovid), The Cochrane Database of Systematic Reviews (Cochrane Library) and Epistemonikos. Two reviewers will independently screen the records identified through the search strategy and extract the information from the included overviews. The frequency and the type of overlap management strategies of the primary studies included in the SRs will be considered as the main outcome. In addition, the recognition of the lack of use of any overlap management strategy and the congruence between planning and conducting the overview focusing on overlap management strategies will be assessed. A subgroup analysis will be carried out according to the journal impact factor, year of publication and compliance with the Preferred Reporting Items for Overviews of Reviews statement. ETHICS AND DISSEMINATION: This study will not involve human subjects and therefore does not require ethics committee approval. However, the conduct and reporting of the findings of this review will be conducted in a rigorous, systematic and transparent manner, which relates to research ethics.The findings of this review will be presented at scientific conferences and published as one or more studies in peer-review scientific journals related to rehabilitation or research methods.

Does type of funding affect reporting in network meta-analysis? A scoping review of network meta-analyses.

BACKGROUND: Evidence has shown that private industry-sponsored randomized controlled trials (RCTs) and meta-analyses are more likely to report intervention-favourable results compared with other sources of funding. However, this has not been assessed in network meta-analyses (NMAs). OBJECTIVES: To (a) explore the recommendation rate of industry-sponsored NMAs on their company's intervention, and (b) assess reporting in NMAs of pharmacologic interventions according to their funding type. METHODS: Design: Scoping review of published NMAs with RCTs. INFORMATION SOURCES: We used a pre-existing NMA database including 1,144 articles from MEDLINE, EMBASE and Cochrane Database of Systematic Reviews, published between January 2013 and July 2018. STUDY SELECTION: NMAs with transparent funding information and comparing pharmacologic interventions with/without placebo. SYNTHESIS: We captured whether NMAs recommended their own or another company's intervention, classified NMAs according to their primary outcome findings (i.e., statistical significance and direction of effect), and according to the overall reported conclusion. We assessed reporting using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension to NMA (PRISMA-NMA) 32-item checklist. We matched and compared industry with non-industry NMAs having the same research question, disease, primary outcome, and pharmacologic intervention against placebo/control. RESULTS: We retrieved 658 NMAs, which reported a median of 23 items in the PRISMA-NMA checklist (interquartile range [IQR]: 21-26). NMAs were categorized as 314 publicly-sponsored (PRISMA-NMA median 24.5, IQR 22-27), 208 non-sponsored (PRISMA-NMA median 23, IQR 20-25), and 136 industry/mixed-sponsored NMAs (PRISMA-NMA median 21, IQR 19-24). Most industry-sponsored NMAs recommended their own manufactured drug (92%), suggested a statistically significant positive treatment-effect for their drug (82%), and reported an overall positive conclusion (92%). Our matched NMAs (25 industry vs 25 non-industry) indicated that industry-sponsored NMAs had favourable conclusions more often (100% vs 80%) and were associated with larger (but not statistically significantly different) efficacy effect sizes (in 61% of NMAs) compared with non-industry-sponsored NMAs. CONCLUSIONS: Differences in completeness of reporting and author characteristics were apparent among NMAs with different types of funding. Publicly-sponsored NMAs had the best reporting and published their findings in higher impact-factor journals. Knowledge users should be mindful of this potential funding bias in NMAs.

Systematic reviewers used various approaches to data extraction and expressed several research needs: a survey.

OBJECTIVE: Data extraction is a prerequisite for analyzing, summarizing, and interpreting evidence in systematic reviews. Yet guidance is limited, and little is known about current approaches. We surveyed systematic reviewers on their current approaches to data extraction, opinions on methods, and research needs. STUDY DESIGN AND SETTING: We developed a 29-question online survey and distributed it through relevant organizations, social media, and personal networks in 2022. Closed questions were evaluated using descriptive statistics, and open questions were analyzed using content analysis. RESULTS: 162 reviewers participated. Use of adapted (65%) or newly developed extraction forms (62%) was common. Generic forms were rarely used (14%). Spreadsheet software was the most popular extraction tool (83%). Piloting was reported by 74% of respondents and included a variety of approaches. Independent and duplicate extraction was considered the most appropriate approach to data collection (64%). About half of respondents agreed that blank forms and/or raw data should be published. Suggested research gaps were the effects of different methods on error rates (60%) and the use of data extraction support tools (46%). CONCLUSION: Systematic reviewers used varying approaches to pilot data extraction. Methods to reduce errors and use of support tools such as (semi-)automation tools are top research gaps.

Clinical utility of overviews on adverse events of pharmacological interventions.

BACKGROUND: Overviews (i.e., systematic reviews of systematic reviews, meta-reviews, umbrella reviews) are a relatively new type of evidence synthesis. Among others, one reason to conduct an overview is to investigate adverse events (AEs) associated with a healthcare intervention. Overviews aim to provide easily accessible information for healthcare decision-makers including clinicians. We aimed to evaluate the clinical utility of overviews investigating AEs. METHODS: We used a sample of 27 overviews exclusively investigating drug-related adverse events published until 2021 identified in a prior project. We defined clinical utility as the extent to which overviews are perceived to be useful in clinical practice. Each included overview was assigned to one of seven pharmacological experts with expertise on the topic of the overview. The clinical utility and value of these overviews were determined using a self-developed assessment tool. This included four open-ended questions and a ranking of three clinical utility statements completed by clinicians. We calculated frequencies for the ranked clinical utility statements and coded the answers to the open-ended questions using an inductive approach. RESULTS: The overall agreement with the provided statements was high. According to the assessments, 67% of the included overviews generated new knowledge. In 93% of the assessments, the overviews were found to add value to the existing literature. The overviews were rated as more useful than the individual included systematic reviews (SRs) in 85% of the assessments. The answers to the open-ended questions revealed two key aspects of clinical utility in the included overviews. Firstly, it was considered useful that they provide a summary of available evidence (e.g., along with additional assessments, or across different populations, or in different settings that have not been evaluated together in the included SRs). Secondly, it was found useful if overviews conducted a new meta-analysis to answer specific research questions that had not been answered previously. CONCLUSIONS: Overviews on drug-related AEs are considered valuable for clinical practice by clinicians. They can make available evidence on AEs more accessible and provide a comprehensive view of available evidence. As the role of overviews evolves, investigations such as this can identify areas of value.

Can routinely collected administrative data effectively be used to evaluate and validate endpoints used in breast cancer clinical trials? Protocol for a scoping review of the literature.

BACKGROUND: Randomized controlled trials (RCTs) are a critical component of evidence-based medicine and the evolution of patient care. However, the costs of conducting a RCT can be prohibitive. A promising approach toward reduction of costs and lessening of the burden of intensive and lengthy patient follow-up is the use of routinely collected healthcare data (RCHD), commonly called real-world data. We propose a scoping review to identify existing RCHD case definitions of breast cancer progression and survival and their diagnostic performance. METHODS: We will search MEDLINE, EMBASE, and CINAHL to identify primary studies of women with either early-stage or metastatic breast cancer, managed with established therapies, that evaluated the diagnostic accuracy of one or more RCHD-based case definitions or algorithms of disease progression (i.e., recurrence, progression-free survival, disease-free survival, or invasive disease-free survival) or survival (i.e., breast-cancer-free survival or overall survival) compared with a reference standard measure (e.g., chart review or a clinical trial dataset). Study characteristics and descriptions of algorithms will be extracted along with measures of the diagnostic accuracy of each algorithm (e.g., sensitivity, specificity, positive predictive value, negative predictive value), which will be summarized both descriptively and in structured figures/tables. DISCUSSION: Findings from this scoping review will be clinically meaningful for breast cancer researchers globally. Identification of feasible and accurate strategies to measure patient-important outcomes will potentially reduce RCT budgets as well as lessen the burden of intensive trial follow-up on patients. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework ( https://doi.org/10.17605/OSF.IO/6D9RS ).

Use of existing systematic reviews for the development of evidence-based vaccination recommendations: Guidance from the SYSVAC expert panel.

National immunization technical advisory groups (NITAGs) develop immunization-related recommendations and assist policy-makers in making evidence informed decisions. Systematic reviews (SRs) that summarize the available evidence on a specific topic are a valuable source of evidence in the development of such recommendations. However, conducting SRs requires significant human, time, and financial resources, which many NITAGs lack. Given that SRs already exist for many immunization-related topics, and to prevent duplication and overlap of reviews, a more practical approach may be for NITAGs to use existing SRs. Nevertheless, it can be challenging to identify relevant SRs, to select one SR from among multiple SRs, or to critically assess and effectively use them. To support NITAGs, the London School of Hygiene and Tropical Medicine, Robert Koch Institute and collaborators developed the SYSVAC project, which consists of an online registry of systematic reviews on immunization-related topics and an e-learning course, that supports the use of them (both freely accessible at https://www.nitag-resource.org/sysvac-systematic-reviews). Drawing from the e-learning course and recommendations from an expert panel, this paper outlines methods for using existing systematic reviews when making immunization-related recommendations. With specific examples and reference to the SYSVAC registry and other resources, it offers guidance on locating existing systematic reviews; assessing their relevance to a research question, up-to-dateness, and methodological quality and/or risk of bias; and considering the transferability and applicability of their findings to other populations or settings.