ObjectiveTo compare the effects of treatments for coronavirus disease 2019 (covid-19).DesignLiving systematic review and network meta-analysis.Data sourcesUS Centers for Disease Control and Prevention COVID-19 Research Articles Downloadable Database, which includes 25 electronic databases and six additional Chinese databases to 20 July 2020.Study selectionRandomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.MethodsAfter duplicate data abstraction, a bayesian random effects network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.Results23 randomised controlled trials were included in the analysis performed on 26 June 2020. The certainty of the evidence for most comparisons was very low because of risk of bias (lack of blinding) and serious imprecision. Glucocorticoids were the only intervention with evidence for a reduction in death compared with standard care (risk difference 37 fewer per 1000 patients, 95% credible interval 63 fewer to 11 fewer, moderate certainty) and mechanical ventilation (31 fewer per 1000 patients, 47 fewer to 9 fewer, moderate certainty). These estimates are based on direct evidence; network estimates for glucocorticoids compared with standard care were less precise because of network heterogeneity. Three drugs might reduce symptom duration compared with standard care: hydroxychloroquine (mean difference −4.5 days, low certainty), remdesivir (−2.6 days, moderate certainty), and lopinavir-ritonavir (−1.2 days, low certainty). Hydroxychloroquine might increase the risk of adverse events compared with the other interventions, and remdesivir probably does not substantially increase the risk of adverse effects leading to drug discontinuation. No other interventions included enough patients to meaningfully interpret adverse effects leading to drug discontinuation.ConclusionGlucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important study limitations.Systematic review registrationThis review was not registered. The protocol is included as a supplement.Readers’ noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Objective To provide guidance for the management of gout, including indications for and optimal use of urate‐lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations. Methods Fifty‐seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta‐analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional. Results Forty‐two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first‐line ULT, including for those with moderate‐to‐severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat‐to‐target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3–6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended. Conclusion Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.

Objective To provide guidance for the management of gout, including indications for and optimal use of urate‐lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations. Methods Fifty‐seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta‐analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional. Results Forty‐two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first‐line ULT, including for those with moderate‐to‐severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat‐to‐target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3–6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended. Conclusion Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.

Objective To develop an instrument to evaluate the credibility of anchor based minimal important differences (MIDs) for outcome measures reported by patients, and to assess the reliability of the instrument. Design Instrument development and reliability study. Data sources Initial criteria were developed for evaluating the credibility of anchor based MIDs based on a literature review (Medline, Embase, CINAHL, and PsycInfo databases) and the experience of the authors in the methodology for estimation of MIDs. Iterative discussions by the team and pilot testing with experts and potential users facilitated the development of the final instrument. Participants With the newly developed instrument, pairs of masters, doctoral, or postdoctoral students with a background in health research methodology independently evaluated the credibility of a sample of MID estimates. Main outcome measures Core credibility criteria applicable to all anchor types, additional criteria for transition rating anchors, and inter-rater reliability coefficients were determined. Results The credibility instrument has five core criteria: the anchor is rated by the patient; the anchor is interpretable and relevant to the patient; the MID estimate is precise; the correlation between the anchor and the outcome measure reported by the patient is satisfactory; and the authors select a threshold on the anchor that reflects a small but important difference. The additional criteria for transition rating anchors are: the time elapsed between baseline and follow-up measurement for estimation of the MID is optimal; and the correlations of the transition rating with the baseline, follow-up, and change score in the patient reported outcome measures are satisfactory. Inter-rater reliability coefficients (ĸ) for the core criteria and for one item from the additional criteria ranged from 0.70 to 0.94. Reporting issues prevented the evaluation of the reliability of the three other additional criteria for the transition rating anchors. Conclusions Researchers, clinicians, and healthcare policy decision makers can consider using this instrument to evaluate the design, conduct, and analysis of studies estimating anchor based minimal important differences.