Explore the vast range of titles available.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread person-to-person through close contact. We aimed to investigate the effects of physical distance, face masks, and eye protection on virus transmission in health-care and non-health-care (eg, community) settings. We did a systematic review and meta-analysis to investigate the optimum distance for avoiding person-to-person virus transmission and to assess the use of face masks and eye protection to prevent transmission of viruses. We obtained data for SARS-CoV-2 and the betacoronaviruses that cause severe acute respiratory syndrome, and Middle East respiratory syndrome from 21 standard WHO-specific and COVID-19-specific sources. We searched these data sources from database inception to May 3, 2020, with no restriction by language, for comparative studies and for contextual factors of acceptability, feasibility, resource use, and equity. We screened records, extracted data, and assessed risk of bias in duplicate. We did frequentist and Bayesian meta-analyses and random-effects meta-regressions. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study is registered with PROSPERO, CRD42020177047. Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25 697 patients). Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m (n=10 736, pooled adjusted odds ratio [aOR] 0·18, 95% CI 0·09 to 0·38; risk difference [RD] −10·2%, 95% CI −11·5 to −7·5; moderate certainty); protection was increased as distance was lengthened (change in relative risk [RR] 2·02 per m; pinteraction=0·041; moderate certainty). Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0·15, 95% CI 0·07 to 0·34, RD −14·3%, −15·9 to −10·7; low certainty), with stronger associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12–16-layer cotton masks; pinteraction=0·090; posterior probability >95%, low certainty). Eye protection also was associated with less infection (n=3713; aOR 0·22, 95% CI 0·12 to 0·39, RD −10·6%, 95% CI −12·5 to −7·7; low certainty). Unadjusted studies and subgroup and sensitivity analyses showed similar findings. The findings of this systematic review and meta-analysis support physical distancing of 1 m or more and provide quantitative estimates for models and contact tracing to inform policy. Optimum use of face masks, respirators, and eye protection in public and health-care settings should be informed by these findings and contextual factors. Robust randomised trials are needed to better inform the evidence for these interventions, but this systematic appraisal of currently best available evidence might inform interim guidance. World Health Organization.

Correspondence to: A D Oxman oxman@online.no Summary points Clinicians, guideline developers, and policymakers sometimes neglect important criteria, give undue weight to criteria, and do not use the best available evidence to inform their judgments Explicit and transparent systems for decision making can help to ensure that all important criteria are considered and that decisions are informed by the best available research evidence The purpose of Evidence to Decision (EtD) frameworks is to help people use evidence in a structured and transparent way to inform decisions in the context of clinical recommendations, coverage decisions, and health system or public health recommendations and decisions EtD frameworks have a common structure that includes formulation of the question, an assessment of the evidence, and drawing conclusions, though there are some differences between frameworks for each type of decision EtD frameworks inform users about the judgments that were made and the evidence supporting those judgments by making the basis for decisions transparent to target audiences EtD frameworks also facilitate dissemination of recommendations and enable decision makers in other jurisdictions to adopt recommendations or decisions, or adapt them to their context Introduction Healthcare decision making is complex. Decision-making processes and the factors (criteria) that decision makers should consider vary for different types of decisions, including clinical recommendations, coverage decisions, and health system or public health recommendations or decisions.1 2 3 4 However, some criteria are relevant for all of these decisions, including the anticipated effects of the options being considered, the certainty of the evidence for those effects (also referred to as quality of evidence or confidence in effect estimates), and the costs and feasibility of the options. Rigorously developed guidelines synthesise the available relevant research, facilitating the translation of evidence into recommendations for clinical practice.9 However, the quality of guidelines is often suboptimal.10 11 If guidelines are not developed systematically and transparently, clinicians are not able to decide whether to rely on them or to explore disagreements when faced with conflicting recommendations.12 The GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group has previously developed and refined a system to assess the certainty of evidence of effects and strength of recommendations.13 14 15 More than 100 organisations globally, including the World Health Organization, the Cochrane Collaboration, and the National Institute for Health and Care Excellence (NICE) now use or have adopted the principles of the GRADE system. Cure by 120 weeks, adverse drug reactions (clinical and biological serious adverse events), mortality, time to culture conversion, culture conversion at 24 weeks, acquired resistance to fluoroquinolone and injectable drugs Setting: Global, MDR-TB clinics Perspective: Population perspective (health system) Subgroups: Patients with extensively drug-resistant (XDR) or pre-XDR tuberculosis or those with resistance or contraindication to fluoroquinolones or injectables Background: The emergence of drug resistance is a major threat to global tuberculosis care and control.

Correspondence to: P Alonso-Coello palonso@santpau.cat Summary points Clinicians do not have the time or resources to consider the underlying evidence for the myriad decisions they must make each day and, as a consequence, rely on recommendations from clinical practice guidelines Guideline panels should consider all the relevant factors (criteria) that influence a decision or recommendation in a structured, explicit, and transparent way and provide clinicians with clear and actionable recommendations The GRADE working group has developed Evidence to Decision (EtD) frameworks for different types of decisions and recommendations. In this article we will describe EtD frameworks for clinical practice recommendations The general structure of the EtD framework for clinical recommendations is similar to EtD frameworks for other types of recommendations and decisions, and includes formulation of the question, an assessment of the different criteria, and conclusions Clinical recommendations require considering criteria differently, depending on whether an individual patient or a population perspective is taken. To ensure trustworthiness, clinical practice guidelines are made by groups of people (guideline panels) with relevant skills, perspectives, and knowledge; they are informed by the best available evidence; and they are systematically developed.1 2 3 4 In the first article in this series, we described GRADE Evidence to Decision (EtD) frameworks and their rationale for different types of decisions.5 In this second article, we describe the use of EtD frameworks for clinical recommendations and how they can help clinicians and patients who use those recommendations. Death, stroke, major bleeding, myocardial infarction, treatment burden Setting: High resource setting Perspective: Health system Subgroups: Patients who are well controlled with warfarin Background: Warfarin reduces the risk for ischaemic stroke in patients with atrial fibrillation but increases the risk for haemorrhage and requires frequent blood tests and clinic visits to monitor the international normalised ratio (INR) and adjust the dose.

The aim of this study is to provide updated guidance on when The Grading of Recommendations Assessment, Development and Evaluation (GRADE) users should consider rating down more than one level for imprecision using a minimally contextualized approach. Based on the first GRADE guidance addressing imprecision rating in 2011, a project group within the GRADE Working Group conducted iterative discussions and presentations at GRADE Working Group meetings to produce this guidance. GRADE suggests aligning imprecision criterion for systematic reviews and guidelines using the approach that relies on thresholds and confidence intervals (CI) of absolute effects as a primary criterion for imprecision rating (i.e., CI approach). Based on the CI approach, when a CI appreciably crosses the threshold(s) of interest, one should consider rating down two or three levels. When the CI does not cross the threshold(s) and the relative effect is large, one should implement the optimal information size (OIS) approach. If the sample size of the meta-analysis is far less than the OIS, one should consider rating down more than one level for imprecision. GRADE provides updated guidance for imprecision rating in a minimally contextualized approach, with a focus on the circumstances in which one should seriously consider rating down two or three levels for imprecision.

This article describes conceptual advances of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group guidance to evaluate the certainty of evidence (confidence in evidence, quality of evidence) from network meta-analysis (NMA). Application of the original GRADE guidance, published in 2014, in a number of NMAs has resulted in advances that strengthen its conceptual basis and make the process more efficient. This guidance will be useful for systematic review authors who aim to assess the certainty of all pairwise comparisons from an NMA and who are familiar with the basic concepts of NMA and the traditional GRADE approach for pairwise meta-analysis. Two principles of the original GRADE NMA guidance are that we need to rate the certainty of the evidence for each pairwise comparison within a network separately and that in doing so we need to consider both the direct and indirect evidence. We present, discuss, and illustrate four conceptual advances: (1) consideration of imprecision is not necessary when rating the direct and indirect estimates to inform the rating of NMA estimates, (2) there is no need to rate the indirect evidence when the certainty of the direct evidence is high and the contribution of the direct evidence to the network estimate is at least as great as that of the indirect evidence, (3) we should not trust a statistical test of global incoherence of the network to assess incoherence at the pairwise comparison level, and (4) in the presence of incoherence between direct and indirect evidence, the certainty of the evidence of each estimate can help decide which estimate to believe. •The application of the Grading of Recommendations Assessments, Development, and Evaluation approach to a number of network meta-analyses in the 3 years since the original guidance publication has led to advances that have strengthened the conceptual basis.•We present, discuss, and illustrate four conceptual advances. These are based on two principles: we need to rate the certainty of the evidence of each pairwise comparison within a network separately and that we need to consider both the direct and indirect evidence contributing to each network estimate.•Although maximizing the efficiency of the process is desirable, as illustrated in the conceptual advances, use of these strategies requires careful judgment.

Oral immunotherapy is an emerging experimental treatment for peanut allergy, but its benefits and harms are unclear. We systematically reviewed the efficacy and safety of oral immunotherapy versus allergen avoidance or placebo (no oral immunotherapy) for peanut allergy. In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, we searched MEDLINE, EMBASE, Cochrane Controlled Register of Trials, Latin American & Caribbean Health Sciences Literature, China National Knowledge Infrastructure, WHO's Clinical Trials Registry Platform, US Food and Drug Administration, and European Medicines Agency databases from inception to Dec 6, 2018, for randomised controlled trials comparing oral immunotherapy versus no oral immunotherapy for peanut allergy, without language restrictions. We screened studies, extracted data, and assessed risk of bias independently in duplicate. Main outcomes included anaphylaxis, allergic or adverse reactions, epinephrine use, and quality of life, meta-analysed by random effects. We assessed certainty (quality) of evidence by the GRADE approach. This study is registered with PROSPERO, number CRD42019117930. 12 trials (n=1041; median age across trials 8·7 years [IQR 5·9–11·2]) showed that oral immunotherapy versus no oral immunotherapy increased anaphylaxis risk (risk ratio [RR] 3·12 [95% CI 1·76–5·55], I2=0%, risk difference [RD] 15·1%, high-certainty), anaphylaxis frequency (incidence rate ratio [IRR] 2·72 [1·57–4·72], I2=0%, RD 12·2%, high-certainty), and epinephrine use (RR 2·21 [1·27–3·83], I2=0%, RD 4·5%, high-certainty) similarly during build-up and maintenance (pinteraction=0·92). Oral immunotherapy increased serious adverse events (RR 1·92 [1·00–3·66], I2=0%, RD 5·7%, moderate-certainty), and non-anaphylactic reactions (vomiting: RR 1·79 [95%CI 1·35–2·38], I2=0%, high-certainty; angioedema: 2·25 [1·13–4·47], I2=0%, high-certainty; upper tract respiratory reactions: 1·36 [1·02–1·81], I2=0%, moderate-certainty; lower tract respiratory reactions: 1·55 [0·96–2·50], I2=28%, moderate-certainty). Passing a supervised challenge, a surrogate for preventing out-of-clinic reactions, was more likely with oral immunotherapy (RR 12·42 [95% CI 6·82–22·61], I2=0%, RD 36·5%, high-certainty). Quality of life was not different between groups (combined parents and self report RR 1·21 [0·87–1·69], I2=0%, RD 0·03%, low-certainty). Findings were robust to IRR, trial sequential, subgroup, and sensitivity analyses. In patients with peanut allergy, high-certainty evidence shows that available peanut oral immunotherapy regimens considerably increase allergic and anaphylactic reactions over avoidance or placebo, despite effectively inducing desensitisation. Safer peanut allergy treatment approaches and rigorous randomised controlled trials that evaluate patient-important outcomes are needed. None.

When studies measure or report outcomes differently, it may not be feasible to pool data across studies to generate a single effect estimate (ie, perform meta-analysis). Instead, only a narrative summary of the effect across different studies might be available. Regardless of whether a single pooled effect estimate is generated or whether data are summarised narratively, decision makers need to know the certainty in the evidence in order to make informed decisions. In this guide, we illustrate how to apply the constructs of the GRADE (Grading of Recommendation, Assessment, Development and Evaluation) approach to assess the certainty in evidence when a meta-analysis has not been performed and data were summarised narratively.

•One of the aims of the Grading of Recommendations Development, Assessment and Evaluation (GRADE) Working Group (GWG) has been to develop a single system that would reduce confusion arising from a legion of multiple conflicting systems for grading evidence and recommendations and serve as unifying lingua franca.•Although GRADE has been widely endorsed, the way it is being used is not infrequently inconsistent with GRADE guidance and some groups have modified the approach.•Based on the suggested criteria for claiming the use and application of GRADE that are available on the GWG website since 2008, we propose 7 items that should be met to appropriately claim that the GRADE approach was used.•These requirements apply to, either assessing certainty of evidence (e.g., in systematic reviews or health technology assessments) and developing recommendations (e.g., in guidelines) or making health care decisions (e.g., coverage, public health or health systems).•The requirements include how the certainty of a body of evidence is defined, assessed for each critical outcome using the GRADE domains, and presented.•Furthermore, they suggest that explicit criteria (both health related and contextual) and evidence as described in the Evidence to Decision (EtD) frameworks should form the basis for recommendations or decisions and explicit judgements should be made for each criterion that is chosen for the EtD process.•A recommendation should have 1 of 2 strengths (strong or conditional, also called weak) and 1 of 2 directions (for or against).•Given these suggested minimal requirements, we also provide a detailed description of the GWG's current methods and processes for developing official GRADE guidance and concept articles, as well as by whom and how they are authored.•Following approval of terms of reference, the methods and process to developing official GRADE articles include: Identification of issues to be addressed through meetings and online communication; iterative presentations to small and larger audiences of multidisciplinary experts in the GWG; identification of real or hypothetical examples; review of the literature on specific topics to identify existing methodological concepts or guidance; presentation to the project group to collect feedback systematically; members of the project group, before presentation to the entire GWG membership for an anonymous vote-based approval; and final approval by the GRADE Guidance Group before peer review and publication.•If the solutions that are described have been applied and deemed appropriately operationalized, GRADE typically develops guidance articles and if they require testing and possibly future alteration, GRADE develops concept articles.

Updating of systematic reviews is generally more efficient than starting all over again when new evidence emerges, but to date there has been no clear guidance on how to do this. This guidance helps authors of systematic reviews, commissioners, and editors decide when to update a systematic review, and then how to go about updating the review.