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 determine and compare the effects of drug prophylaxis on SARS-CoV-2 infection and covid-19. Design Living systematic review and network meta-analysis. Data sources World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 25 March 2021, and six additional Chinese databases to 20 February 2021. Study selection Randomised trials of people at risk of covid-19 who were assigned to receive prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles. Methods Random effects bayesian network meta-analysis was performed after duplicate data abstraction. Included studies were assessed for risk of bias using a modification of the Cochrane risk of bias 2.0 tool, and certainty of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. Results The first iteration of this living network meta-analysis includes nine randomised trials—six of hydroxychloroquine (n=6059 participants), one of ivermectin combined with iota-carrageenan (n=234), and two of ivermectin alone (n=540), all compared with standard care or placebo. Two trials (one of ramipril and one of bromhexine hydrochloride) did not meet the sample size requirements for network meta-analysis. Hydroxychloroquine has trivial to no effect on admission to hospital (risk difference 1 fewer per 1000 participants, 95% credible interval 3 fewer to 4 more; high certainty evidence) or mortality (1 fewer per 1000, 2 fewer to 3 more; high certainty). Hydroxychloroquine probably does not reduce the risk of laboratory confirmed SARS-CoV-2 infection (2 more per 1000, 18 fewer to 28 more; moderate certainty), probably increases adverse effects leading to drug discontinuation (19 more per 1000, 1 fewer to 70 more; moderate certainty), and may have trivial to no effect on suspected, probable, or laboratory confirmed SARS-CoV-2 infection (15 fewer per 1000, 64 fewer to 41 more; low certainty). Owing to serious risk of bias and very serious imprecision, and thus very low certainty of evidence, the effects of ivermectin combined with iota-carrageenan on laboratory confirmed covid-19 (52 fewer per 1000, 58 fewer to 37 fewer), ivermectin alone on laboratory confirmed infection (50 fewer per 1000, 59 fewer to 16 fewer) and suspected, probable, or laboratory confirmed infection (159 fewer per 1000, 165 fewer to 144 fewer) remain very uncertain. Conclusions Hydroxychloroquine prophylaxis has trivial to no effect on hospital admission and mortality, probably increases adverse effects, and probably does not reduce the risk of SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, it is highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection. Systematic review registration This review was not registered. The protocol established a priori is included as a supplement. Readers’ note This 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.

This study compares the effectiveness of pharmacological treatments to develop guidelines for the management of acute pain after tooth extraction. We searched Medline, EMBASE, CENTRAL, and US Clinical Trials registry on November 21, 2020. We included randomized clinical trials (RCTs) of participants undergoing dental extractions comparing 10 interventions, including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and combinations to placebo. After duplicate screening and data abstraction, we conducted a frequentist network meta-analysis for each outcome at 6 h (i.e., pain relief, total pain relief [TOTPAR], summed pain intensity difference [SPID], global efficacy rating, rescue analgesia, and adverse effects). We assessed the risk of bias using a modified Cochrane RoB 2.0 tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We implemented the analyses in RStudio version 3.5.3 and classified interventions from most to least beneficial or harmful. We included 82 RCTs. Fifty-six RCTs enrolling 9,095 participants found moderate- and high-certainty evidence that ibuprofen 200 to 400 mg plus acetaminophen 500 to 1,000 mg (mean difference compared to placebo [MDp], 1.68; 95% confidence interval [CI], 1.06–2.31), acetaminophen 650 mg plus oxycodone 10 mg (MDp, 1.19; 95% CI, 0.85–1.54), ibuprofen 400 mg (MDp, 1.31; 95% CI, 1.17–1.45), and naproxen 400–440 mg (MDp, 1.44; 95% CI, 1.07–1.80) were most effective for pain relief on a 0 to 4 scale. Oxycodone 5 mg, codeine 60 mg, and tramadol 37.5 mg plus acetaminophen 325 mg were no better than placebo. The results for TOTPAR, SPID, global efficacy rating, and rescue analgesia were similar. Based on low- and very low-certainty evidence, most interventions were classified as no more harmful than placebo for most adverse effects. Based on moderate- and high-certainty evidence, NSAIDs with or without acetaminophen result in better pain-related outcomes than opioids with or without acetaminophen (except acetaminophen 650 mg plus oxycodone 10 mg) or placebo.