Endovascular thrombectomy with or without thrombolysis bridging in patients with acute ischaemic stroke: protocol for a systematic review, meta-analysis of randomised trials and cost-effectiveness analysis.

INTRODUCTION: Current published guidelines and meta-analyses comparing endovascular thrombectomy (EVT) alone versus EVT with bridging intravenous thrombolysis (IVT) suggest that EVT alone is non-inferior to EVT with bridging thrombolysis in achieving favourable functional outcome. Because of this controversy, we aimed to systematically update the evidence and meta-analyse data from randomised trials comparing EVT alone versus EVT with bridging thrombolysis, and performed an economic evaluation comparing both strategies. METHODS AND ANALYSIS: We will conduct a systematic review of randomised controlled trials comparing EVT with or without bridging thrombolysis in patients presenting with large vessel occlusions. We will identify eligible studies by systematically searching the following databases from inception without any language restrictions: MEDLINE (through Ovid), Embase and the Cochrane Library. The following criteria will be used to assess eligibility for inclusion: (1) adult patients ≥18 years old; (2) randomised patients to EVT alone or to EVT with IVT; and (3) measured outcomes, including functional outcomes, at least 90 days after randomisation. Pairs of reviewers will independently screen the identified articles, extract information and assess the risk of bias of eligible studies. We will use the Cochrane Risk-of-Bias tool to evaluate risk of bias. We will also use the Grading of Recommendations, Assessment, Development and Evaluation approach to assess the certainty in evidence for each outcome. We will then perform an economic evaluation based on the extracted data. ETHICS AND DISSEMINATION: This systematic review will not require a research ethics approval because no confidential patient data will be used. We will disseminate our findings by publishing the results in a peer-reviewed journal and via presentation at conferences. PROSPERO REGISTRATION NUMBER: CRD42022315608.

The life and death of living systematic reviews: a methodological survey.

OBJECTIVES: The objectives of this study are to describe the characteristics of living systematic reviews (LSRs) and to understand their life cycles. STUDY DESIGN AND SETTING: We conducted a comprehensive search up to April 2021 then selected articles and abstracted data in duplicate and independently. We undertook descriptive analyses and calculated delay in version update and delay since the last published version. RESULTS: We included 76 eligible LSRs with a total of 279 eligible versions. The majority of LSRs was from the clinical field (70%), was COVID-19 related (63%), and had a funding source specified (62%). The median number of versions per LSR was 2 (interquartile range (IQR) 1-4; range 1-19). The median and IQR for the ratio of the actual period of update to the planned period of update was 1.12 (0.81; 1.71). Out of all reviews with a 'planned period of update' and at least one update (N = 19), eight LSRs (42%) had a period since last published version greater than 3 times the planned period of update. No LSR included a 'retirement notice' in their latest published version. CONCLUSION: While most LSR complied with the planned period of producing updates, a substantive proportion lagged since their last update.

Inspiratory muscle training, with or without concomitant pulmonary rehabilitation, for chronic obstructive pulmonary disease (COPD).

BACKGROUND: Inspiratory muscle training (IMT) aims to improve respiratory muscle strength and endurance. Clinical trials used various training protocols, devices and respiratory measurements to check the effectiveness of this intervention. The current guidelines reported a possible advantage of IMT, particularly in people with respiratory muscle weakness. However, it remains unclear to what extent IMT is clinically beneficial, especially when associated with pulmonary rehabilitation (PR).   OBJECTIVES: To assess the effect of inspiratory muscle training (IMT) on chronic obstructive pulmonary disease (COPD), as a stand-alone intervention and when combined with pulmonary rehabilitation (PR). SEARCH METHODS: We searched the Cochrane Airways trials register, CENTRAL, MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCO, Physiotherapy Evidence Database (PEDro) ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 20 October 2021. We also checked reference lists of all primary studies and review articles. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared IMT in combination with PR versus PR alone and IMT versus control/sham. We included different types of IMT irrespective of the mode of delivery. We excluded trials that used resistive devices without controlling the breathing pattern or a training load of less than 30% of maximal inspiratory pressure (PImax), or both. DATA COLLECTION AND ANALYSIS: We used standard methods recommended by Cochrane including assessment of risk of bias with RoB 2. Our primary outcomes were dyspnea, functional exercise capacity and health-related quality of life.  MAIN RESULTS: We included 55 RCTs in this review. Both IMT and PR protocols varied significantly across the trials, especially in training duration, loads, devices, number/ frequency of sessions and the PR programs. Only eight trials were at low risk of bias. PR+IMT versus PR We included 22 trials (1446 participants) in this comparison. Based on a minimal clinically important difference (MCID) of -1 unit, we did not find an improvement in dyspnea assessed with the Borg scale at submaximal exercise capacity (mean difference (MD) 0.19, 95% confidence interval (CI) -0.42 to 0.79; 2 RCTs, 202 participants; moderate-certainty evidence).   We also found no improvement in dyspnea assessed with themodified Medical Research Council dyspnea scale (mMRC) according to an MCID between -0.5 and -1 unit (MD -0.12, 95% CI -0.39 to 0.14; 2 RCTs, 204 participants; very low-certainty evidence).  Pooling evidence for the 6-minute walk distance (6MWD) showed an increase of 5.95 meters (95% CI -5.73 to 17.63; 12 RCTs, 1199 participants; very low-certainty evidence) and failed to reach the MCID of 26 meters. In subgroup analysis, we divided the RCTs according to the training duration and mean baseline PImax. The test for subgroup differences was not significant. Trials at low risk of bias (n = 3) demonstrated a larger effect estimate than the overall. The summary effect of the St George's Respiratory Questionnaire (SGRQ) revealed an overall total score below the MCID of 4 units (MD 0.13, 95% CI -0.93 to 1.20; 7 RCTs, 908 participants; low-certainty evidence).  The summary effect of COPD Assessment Test (CAT) did not show an improvement in the HRQoL (MD 0.13, 95% CI -0.80 to 1.06; 2 RCTs, 657 participants; very low-certainty evidence), according to an MCID of -1.6 units.  Pooling the RCTs that reported PImax showed an increase of 11.46 cmH2O (95% CI 7.42 to 15.50; 17 RCTs, 1329 participants; moderate-certainty evidence) but failed to reach the MCID of 17.2 cmH2O.  In subgroup analysis, we did not find a difference between different training durations and between studies judged with and without respiratory muscle weakness.  One abstract reported some adverse effects that were considered "minor and self-limited". IMT versus control/sham Thirty-seven RCTs with 1021 participants contributed to our second comparison. There was a trend towards an improvement when Borg was calculated at submaximal exercise capacity (MD -0.94, 95% CI -1.36 to -0.51; 6 RCTs, 144 participants; very low-certainty evidence). Only one trial was at a low risk of bias. Eight studies (nine arms) used the Baseline Dyspnea Index - Transition Dyspnea Index (BDI-TDI). Based on an MCID of +1 unit, they showed an improvement only with the 'total score' of the TDI (MD 2.98, 95% CI 2.07 to 3.89; 8 RCTs, 238 participants; very low-certainty evidence). We did not find a difference between studies classified as with and without respiratory muscle weakness. Only one trial was at low risk of bias. Four studies reported the mMRC, revealing a possible improvement in dyspnea in the IMT group (MD -0.59, 95% CI -0.76 to -0.43; 4 RCTs, 150 participants; low-certainty evidence). Two trials were at low risk of bias. Compared to control/sham, the MD in the 6MWD following IMT was 35.71 (95% CI 25.68 to 45.74; 16 RCTs, 501 participants; moderate-certainty evidence). Two studies were at low risk of bias. In subgroup analysis, we did not find a difference between different training durations and between studies judged with and without respiratory muscle weakness.  Six studies reported theSGRQ total score, showing a larger effect in the IMT group (MD -3.85, 95% CI -8.18 to 0.48; 6 RCTs, 182 participants; very low-certainty evidence). The lower limit of the 95% CI exceeded the MCID of -4 units. Only one study was at low risk of bias. There was an improvement in life quality with CAT (MD -2.97, 95% CI -3.85 to -2.10; 2 RCTs, 86 participants; moderate-certainty evidence). One trial was at low risk of bias. Thirty-two RCTs reported PImax, showing an improvement without reaching the MCID (MD 14.57 cmH2O, 95% CI 9.85 to 19.29; 32 RCTs, 916 participants; low-certainty evidence). In subgroup analysis, we did not find a difference between different training durations and between studies judged with and without respiratory muscle weakness.   None of the included RCTs reported adverse events. AUTHORS' CONCLUSIONS: IMT may not improve dyspnea, functional exercise capacity and life quality when associated with PR. However, IMT is likely to improve these outcomes when provided alone. For both interventions, a larger effect in participants with respiratory muscle weakness and with longer training durations is still to be confirmed.

Abdominal Visceral Adipose Tissue and All-Cause Mortality: A Systematic Review.

Introduction: Increased abdominal visceral adipose tissue (VAT) implies an adverse cardio-metabolic profile. We examined the association of abdominal VAT parameters and all-cause mortality risk. Methods: We systematically searched four databases. We performed citations/articles screening, data abstraction, and quality assessment in duplicate and independently (CRD42020205021). Results: We included 12 cohorts, the majority used computed tomography to assess abdominal VAT area. Six cohorts with a mean age ≤ 65 years, examining all-cause mortality risk per increment in VAT area (cm2) or volume (cm3), showed a 11-98% relative risk increase with higher VAT parameters. However, the association lost significance after adjusting for glycemic indices, body mass index, or other fat parameters. In 4 cohorts with a mean age >65 years, the findings on mortality were inconsistent. Conversely, in two cohorts (mean age 73-77 years), a higher VAT density, was inversely proportional to VAT area, and implied a higher mortality risk. Conclusion: A high abdominal VAT area seems to be associated with increased all-cause mortality in individuals ≤ 65 years, possibly mediated by metabolic complications, and not through an independent effect. This relationship is weaker and may reverse in older individuals, most likely secondary to confounding bias and reverse causality. An individual participant data meta-analysis is needed to confirm our findings, and to define an abdominal VAT area cutoff implying increased mortality risk. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=205021, identifier CRD42020205021.

A Framework for the Development of Living Practice Guidelines in Health Care.

BACKGROUND: Living practice guidelines are increasingly being used to ensure that recommendations are responsive to rapidly emerging evidence. OBJECTIVE: To develop a framework that characterizes the processes of development of living practice guidelines in health care. DESIGN: First, 3 background reviews were conducted: a scoping review of methods papers, a review of handbooks of guideline-producing organizations, and an analytic review of selected living practice guidelines. Second, the core team drafted the first version of the framework. Finally, the core team refined the framework through an online survey and online discussions with a multidisciplinary international group of stakeholders. SETTING: International. PARTICIPANTS: Multidisciplinary group of 51 persons who have experience with guidelines. MEASUREMENTS: Not applicable. RESULTS: A major principle of the framework is that the unit of update in a living guideline is the individual recommendation. In addition to providing definitions, the framework addresses several processes. The planning process should address the organization's adoption of the living methodology as well as each specific guideline project. The production process consists of initiation, maintenance, and retirement phases. The reporting should cover the evidence surveillance time stamp, the outcome of reassessment of the body of evidence (when applicable), and the outcome of revisiting a recommendation (when applicable). The dissemination process may necessitate the use of different venues, including one for formal publication. LIMITATION: This study does not provide detailed or practical guidance for how the described concepts would be best implemented. CONCLUSION: The framework will help guideline developers in planning, producing, reporting, and disseminating living guideline projects. It will also help research methodologists study the processes of living guidelines. PRIMARY FUNDING SOURCE: None.

Long Term Weight Loss Diets and Obesity Indices: Results of a Network Meta-Analysis.

Background: Scientists have been investigating efficient interventions to prevent and manage obesity. This network meta-analysis (NMA) compared the effect of different diets [moderate macronutrients (MMs), low fat/high carbohydrate (LFHC), high fat/low carbohydrate (HFLC), and usual diet (UD)] on weight, body mass index (BMI), and waist circumference (WC) changes at ≥12 months. Methods: We searched Medline, Embase, PubMed databases, and the Cochrane Library. We systematically assessed randomized controlled trials (RCTs) evaluating dietary interventions on adults (mean BMI ≥ 25 kg/m2) receiving active dietary counseling for ≥12 months. We pooled the data using a random-effect NMA. We assessed the quality of the included RCTs using the Cochrane risk of bias (ROB) tool. Results: We included 36 trials, 14 of which compared HFLC with MM diets. Compared with UD, all diets were associated with a significant weight loss (WL) at ≥12 months, HFLC [mean difference in kg (95% CI): -5.5 (-7.6; -3.4)], LFHC [-5.0 (-7.1; -2.9)] and MM [-4.7 (-6.8; -2.7)]. HFLC, compared with MM diet, was associated with a slightly higher WL (of -0.77 kg) and drop in BMI (of -0.36 kg/m2), while no significant difference was detected in other dietary comparisons. WC was lower with all diets compared to UD, with no significant difference across specific diets. There was no significant interaction of the results with the pre-specified sub-groups. The ROB was moderate to high, mostly related to unclear allocation concealment, high dropout rate and unclear or lack of blinding of participants, providers, and outcome assessors. Conclusion: Dietary interventions extending over ≥12 months are superior to UD in inducing weight, BMI and WC loss. HFLC might be associated with a slightly higher WL compared with MM diets. Systematic Trial Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=103116, PROSPERO (CRD42018103116).

Adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomised trials.

BACKGROUND: To summarise specific adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir in patients with COVID-19. METHODS: We searched 32 databases through 27 October 2020. We included randomised trials comparing any of the drugs of interest to placebo or standard care, or against each other. We conducted fixed-effects pairwise meta-analysis and assessed the certainty of evidence using the grading of recommendations assessment, development and evaluation approach. RESULTS: We included 16 randomised trials which enrolled 8152 patients. For most interventions and outcomes the certainty of the evidence was very low to low except for gastrointestinal adverse effects from hydroxychloroquine, which was moderate certainty. Compared with standard care or placebo, low certainty evidence suggests that remdesivir may not have an important effect on acute kidney injury (risk difference (RD) 8 fewer per 1000, 95% CI 27 fewer to 21 more) or cognitive dysfunction/delirium (RD 3 more per 1000, 95% CI 12 fewer to 19 more). Low certainty evidence suggests that hydroxychloroquine may increase the risk of cardiac toxicity (RD 10 more per 1000, 95% CI 0 more to 30 more) and cognitive dysfunction/delirium (RD 33 more per 1000, 95% CI 18 fewer to 84 more), whereas moderate certainty evidence suggests hydroxychloroquine probably increases the risk of diarrhoea (RD 106 more per 1000, 95% CI 48 more to 175 more) and nausea and/or vomiting (RD 62 more per 1000, 95% CI 23 more to 110 more) compared with standard care or placebo. Low certainty evidence suggests lopinavir/ritonavir may increase the risk of diarrhoea (RD 168 more per 1000, 95% CI 58 more to 330 more) and nausea and/or vomiting (RD 160 more per 1000, 95% CI 100 more to 210 more) compared with standard care or placebo. DISCUSSION: Hydroxychloroquine probably increases the risk of diarrhoea and nausea and/or vomiting and may increase the risk of cardiac toxicity and cognitive dysfunction/delirium. Lopinavir/ritonavir may increase the risk of diarrhoea and nausea and/or vomiting. Remdesivir may have no important effect on risk of acute kidney injury or cognitive dysfunction/delirium. These findings provide important information to support the development of evidence-based management strategies for patients with COVID-19.

Use of tocilizumab and sarilumab alone or in combination with corticosteroids for covid-19: systematic review and network meta-analysis.

Objective: To compare the effects of interleukin 6 receptor blockers, tocilizumab and sarilumab, with or without corticosteroids, on mortality in patients with covid-19. Design: Systematic review and network meta-analysis. Data sources: World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature, and two prospective meta-analyses (up to 9 June 2021). Review methods: Trials in which people with suspected, probable, or confirmed covid-19 were randomised to interleukin 6 receptor blockers (with or without corticosteroids), corticosteroids, placebo, or standard care. The analysis used a bayesian framework and assessed the certainty of evidence using the GRADE approach. Results from the fixed effect meta-analysis were used for the primary analysis. Results: Of 45 eligible trials (20 650 patients) identified, 36 (19 350 patients) could be included in the network meta-analysis. Of 36 trials, 27 were at high risk of bias, primarily due to lack of blinding. Tocilizumab, in combination with corticosteroids, suggested a reduction in the risk of death compared with corticosteroids alone (odds ratio 0.79, 95% credible interval 0.70 to 0.88; 35 fewer deaths per 1000 people, 95% credible interval 52 fewer to 18 fewer per 1000; moderate certainty of evidence), as did sarilumab in combination with corticosteroids, compared with corticosteroids alone (0.73, 0.58 to 0.92; 43 fewer per 1000, 73 fewer to 12 fewer; low certainty). Tocilizumab and sarilumab, each in combination with corticosteroids, appeared to have similar effects on mortality when compared with each other (1.07, 0.86 to 1.34; eight more per 1000, 20 fewer to 35 more; low certainty). The effects of tocilizumab (1.12, 0.91 to 1.38; 20 more per 1000, 16 fewer to 59 more; low certainty) and sarilumab (1.07, 0.81 to 1.40; 11 more per 1000, 38 fewer to 55 more; low certainty), when used alone, suggested an increase in the risk of death. Conclusion: These findings suggest that in patients with severe or critical covid-19, tocilizumab, in combination with corticosteroids, probably reduces mortality, and that sarilumab, in combination with corticosteroids, might also reduce mortality. Tocilizumab and sarilumab, in combination with corticosteroids, could have similar effectiveness. Tocilizumab and sarilumab, when used alone, might not be beneficial.

COVID-19 transmission during swimming-related activities: a rapid systematic review.

BACKGROUND: There are uncertainties about mitigating strategies for swimming-related activities in the context of the COVID-19 pandemic. There is an opportunity to learn from the experience of previous re-openings to better plan the future one. Our objectives are to systematically review the evidence on (1) the association between engaging in swimming-related activities and COVID-19 transmission; and (2) the effects of strategies for preventing COVID-19 transmission during swimming-related activities. METHODS: We conducted a rapid systematic review. We searched in the L·OVE (Living OVerview of Evidence) platform for COVID-19. The searches covered the period from the inception date of each database until April 19, 2021. We included non-randomized studies for the review on association of COVID-19 transmission and swimming-related activities. We included guidance documents reporting on the strategies for prevention of COVID-19 transmission during swimming-related activities. We also included studies on the efficacy and safety of the strategies. Teams of two reviewers independently assessed article eligibility. For the guidance documents, a single reviewer assessed the eligibility and a second reviewer verified the judgement. Teams of two reviewers extracted data independently. We summarized the findings of included studies narratively. We synthesized information from guidance documents according to the identified topics and subtopics, and presented them in tabular and narrative formats. RESULTS: We identified three studies providing very low certainty evidence for the association between engaging in swimming-related activities and COVID-19 transmission. The analysis of 50 eligible guidance documents identified 11 topics: ensuring social distancing, ensuring personal hygiene, using personal protective equipment, eating and drinking, maintaining the pool, managing frequently touched surfaces, ventilation of indoor spaces, screening and management of sickness, delivering first aid, raising awareness, and vaccination. One study assessing the efficacy of strategies to prevent COVID-19 transmission did not find an association between compliance with precautionary restrictions and COVID-19 transmission. CONCLUSIONS: There are major gaps in the research evidence of relevance to swimming-related activities in the context of the COVID-19 pandemic. However, the synthesis of the identified strategies from guidance documents can inform public health management strategies for swimming-related activities, particularly in future re-opening plans.

Implementing person-centred outcome measures (PCOMs) into routine palliative care: A protocol for a mixed-methods process evaluation of The RESOLVE PCOM Implementation Strategy.

INTRODUCTION: Person-centred outcome measures improve quality of care and patient outcomes but are used inconsistently in palliative care practice. To address this implementation gap, we developed the 'RESOLVE Implementation Strategy'. This protocol describes a process evaluation to explore mechanisms through which this strategy does, or does not, support the implementation of outcome measures in routine palliative care practice. METHODS AND ANALYSIS: Multistrand, mixed-methods process evaluation. Strand one will collect routine outcomes data (palliative Phase of Illness, Integrated Palliative care Outcomes Scale, Australia-modified Karnofsky Performance Status) to map the changes in use of outcome measures over 12 months (July 2021-July 2022). Strand two will collect survey data over the same 12-month period to explore how professionals' understandings of, skills in using and ability to build organisational practices around, outcome measures change over time. Strand three will collect interview data to understand the mechanisms underpinning/affecting our implementation strategy. Thematic framework analysis and descriptive statistics will be used to analyse qualitative and quantitative data, respectively. ETHICS AND DISSEMINATION: For strand one, ethical approval has been obtained (Cambridge REC, REF: 20/EE/0188). For strands two and three, ethical approval has been obtained from Hull York Medical School ethics committee (2105). Tailored feedback of study findings will be provided to participating sites. Abstracts and papers will be submitted to national/international conferences and peer-reviewed journals. Lay and policy briefings and newsletters will be shared through patient and public involvement and project networks, plus via the project website.

Using Parallel Streams of Evidence to Inform Guideline Development: The Case of the 2021 American College of Rheumatology Management of Rheumatoid Arthritis Guideline.

OBJECTIVE: We aim to describe an evidence synthesis approach using parallel streams of evidence that informed the development of the 2021 American College of Rheumatology (ACR) guideline for the management of rheumatoid arthritis (RA). METHODS: We developed the evidence synthesis approach using parallel streams of evidence in multiple rounds of discussion, piloting, feedback, and revisions. A number of working groups involving ACR staff, content experts, and methodologists coordinated to develop and implement the approach. RESULTS: We used a major stream of evidence that identified evidence specific to the clinical questions being addressed in the guideline (ie, we were able to match relevant articles to specific questions). We also used additional streams that identified data that applied across multiple questions. We describe in this article the different steps of the major stream, ie, screening and tagging, matching articles to question clusters, matching articles to individual questions, data abstraction and analysis, and Grading of Recommendations Assessment, Development and Evaluation (GRADEing). We then describe how we packaged the parallel streams of evidence into standardized structured tables to facilitate formulating the recommendations. These tables included information for the following factors: desirable effects, undesirable effects, certainty of evidence, valuation of outcomes, cost of interventions, and cost-effectiveness of interventions. The approach allowed us to match eligible articles for 47 of 81 clinical questions. We identified no eligible articles that addressed the remaining 34 questions. CONCLUSION: We were successful in using parallel streams of evidence to inform the development of the 2021 ACR guideline for the management of RA.

2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.

OBJECTIVE: To develop updated guidelines for the pharmacologic management of rheumatoid arthritis. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional). CONCLUSION: This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients' values, goals, preferences, and comorbidities.

2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.

OBJECTIVE: To develop updated guidelines for the pharmacologic management of rheumatoid arthritis. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional). CONCLUSION: This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients' values, goals, preferences, and comorbidities.

Maternal Education and Low Birth Weight in Low- and Middle-Income Countries: Systematic Review and Meta-Analysis.

OBJECTIVE: Adverse birth outcomes, including low birth weight (LBW), remain the leading causes of child morbidity and mortality in many low- and middle-income countries (LMICs). We carried out a systematic review and meta-analysis to assess the strength and consistency of the association between maternal education and LBW in LMICs. METHODS: We conducted an electronic search of studies published between 2000 and 2014 in four databases using three MeSH keywords - birth outcomes including LBW; individual-level socioeconomic measures including maternal education; and a list of LMICs. The methodological quality of each eligible study was evaluated following the GRADE approach. A total of 26 studies were entered into meta-analysis. Subgroup analyses were performed to account for heterogeneity in the measurement of exposure and country development level. FINDINGS: The meta-analysis revealed a statistically significant pooled estimate (OR = 0.67; 95% CI = 0.61-0.74) indicating that maternal education is protective against LBW in LMICs. Heterogeneity was found high in subgroup analyses in studies from lower-middle income countries and in those measuring maternal education in academic classes, but drops considerably in studies from low-income countries and those measuring it in number of years of schooling. The quality of the overall body of evidence is moderate due to high observed heterogeneity in some subgroup analyses and the presence of studies with high risk of bias. INTERPRETATION: Higher maternal education associates with a moderate but statistically significant decrease in the risk of delivering a LBW infant in LMICs. Enhancing girls' and women's access to education operates through a number of pathways to improve birth outcomes and reduce LBW in LMICs.

The Policies for the Disclosure of Funding and Conflict of Interest in Surgery Journals: A Cross-Sectional Survey.

BACKGROUND: Industry through its funding of research and through its relationships with study authors can influence the results of research. Most journals have policies for reporting funding and disclosing conflict of interest (COI) to mitigate the influence of industry on research. The objective of this study is to assess the policies of surgery journals for the reporting of funding and the disclosure of COI. METHODS: We described the prevalence and characteristics of funding and COI policies of journals indexed under "Surgery" in the Journal Citation Reports. We extracted data from publicly available information and through simulation of manuscript submission. RESULTS: Of the 186 eligible journals, 171 (92%) had policies for reporting of funding. None of the policies described procedures to deal with non-reporting or underreporting of funding. Of the 186 journals, 183 (99%) had a policy for disclosure of COI. All journals with a COI policy required disclosure of financial interest, while 96 (52%) required the disclosure of non-financial interests. Only 24 (13%) policies described how non-disclosure of COI affects the editorial process, and none described procedures to verify COI disclosure. Of the policies that required disclosing COI, 94 (51%) also required reporting the source of financial COI. CONCLUSIONS: Most journals have policies for reporting of funding and disclosure of financial COI. However, many do not have clear policies for disclosing non-financial COI. Major limitations in the policies include the lack of processes for the verification of disclosed interests and for dealing with underreporting of funding and of COI.

Tailored PRISMA 2020 flow diagrams for living systematic reviews: a methodological survey and a proposal.

Background: While the PRISMA flow diagram is widely used for reporting standard systematic reviews (SRs), it was not designed for capturing the results of continual searches for studies in living systematic reviews (LSRs). The objectives of this study are (1) to assess how published LSRs report on the flow of studies through the different phases of the review for the different updates; (2) to propose an approach to reporting on that flow. Methods: For objective 1, we identified all LSRs published up to July 2020. We abstracted information regarding their general characteristics and how they reported on search results. For objective 2, we based our proposal for tailored PRISMA approaches on the findings from objective 1, as well as on our experience with conducting Cochrane LSRs. Results: We identified 108 living publications relating to 32 LSRs. Of the 108 publications, 7% were protocols, 24% were base versions (i.e., the first version), 62% were partial updates (i.e., does not include all typical sections of an SR), and 7% were full updates (i.e., includes all typical sections of an SR). We identified six ways to reporting the study flow: base separately, each update separately (38%); numbers not reported (32%); latest update separately, all previous versions combined (20%); base separately, all updates combined (7%); latest update version only (3%);  all versions combined (0%). We propose recording in detail the results of the searches to keep track of all identified records. For structuring the flow diagram, we propose using one of four approaches. Conclusion: We identified six ways for reporting the study flowthrough the different phases of the review for the different update versions. We propose to document in detail the study flow for the different search updates and select one of our four tailored PRISMA diagram approaches to present that study flow.

Potential impact of missing outcome data on treatment effects in systematic reviews: imputation study.

OBJECTIVE: To assess the risk of bias associated with missing outcome data in systematic reviews. DESIGN: Imputation study. SETTING: Systematic reviews. POPULATION: 100 systematic reviews that included a group level meta-analysis with a statistically significant effect on a patient important dichotomous efficacy outcome. MAIN OUTCOME MEASURES: Median percentage change in the relative effect estimate when applying each of the following assumption (four commonly discussed but implausible assumptions (best case scenario, none had the event, all had the event, and worst case scenario) and four plausible assumptions for missing data based on the informative missingness odds ratio (IMOR) approach (IMOR 1.5 (least stringent), IMOR 2, IMOR 3, IMOR 5 (most stringent)); percentage of meta-analyses that crossed the threshold of the null effect for each method; and percentage of meta-analyses that qualitatively changed direction of effect for each method. Sensitivity analyses based on the eight different methods of handling missing data were conducted. RESULTS: 100 systematic reviews with 653 randomised controlled trials were included. When applying the implausible but commonly discussed assumptions, the median change in the relative effect estimate varied from 0% to 30.4%. The percentage of meta-analyses crossing the threshold of the null effect varied from 1% (best case scenario) to 60% (worst case scenario), and 26% changed direction with the worst case scenario. When applying the plausible assumptions, the median percentage change in relative effect estimate varied from 1.4% to 7.0%. The percentage of meta-analyses crossing the threshold of the null effect varied from 6% (IMOR 1.5) to 22% (IMOR 5) of meta-analyses, and 2% changed direction with the most stringent (IMOR 5). CONCLUSION: Even when applying plausible assumptions to the outcomes of participants with definite missing data, the average change in pooled relative effect estimate is substantive, and almost a quarter (22%) of meta-analyses crossed the threshold of the null effect. Systematic review authors should present the potential impact of missing outcome data on their effect estimates and use this to inform their overall GRADE (grading of recommendations assessment, development, and evaluation) ratings of risk of bias and their interpretation of the results.

Reporting of conflicts of interest by authors of primary studies on health policy and systems research: a cross-sectional survey.

OBJECTIVES: The objective of this study was to assess the frequency and types of conflict of interest (COI) disclosed by authors of primary studies of health policy and systems research (HPSR). DESIGN: We conducted a cross-sectional survey using standard systematic review methodology for study selection and data extraction. We conducted descriptive analyses. SETTING: We collected data from papers published in 2016 in 'health policy and service journals' category in Web of Science database. PARTICIPANTS: We included primary studies (eg, randomised controlled trials, cohort studies, qualitative studies) of HPSR published in English in 2016 peer-reviewed health policy and services journals. OUTCOME MEASURES: Reported COI disclosures including whether authors reported COI or not, form in which COI disclosures were provided, number of authors per paper who report any type of COI, number of authors per paper who report specific types and subtypes of COI. RESULTS: We included 200 eligible primary studies of which 132 (66%) included COI disclosure statements of authors. Of the 132 studies, 19 (14%) had at least one author reporting at least one type of COI and the most frequently reported type was individual financial COI (n=15, 11%). None of the authors reported individual intellectual COIs or personal COIs. Financial and individual COIs were reported more frequently compared with non-financial and institutional COIs. CONCLUSION: A low percentage of HPSR primary studies included authors reporting COI. Non-financial or institutional COIs were the least reported types of COI.