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.
Introduction Kidney transplant recipients are at increased susceptibility to many viral infections leading to justifiable anxiety about the effects of COVID-19. Methods We performed literature searches from multiple resources in April and August 2020 for relevant English and Chinese literature. Abstracts were screened, followed by full-text review with data extraction of reports that included at least 20 kidney transplant recipients with confirmed SARS-CoV-2 infection and completed outcomes. Results Twenty studies had sufficient data which we have summarised. Studies were predominantly descriptive and came from France, Italy, Spain, Turkey, UK, and USA. Quality assessment demonstrated limitations in selection of comparison groups and controlling for additional factors. Mortality rates from published studies were variable. Based on early data early from Spain, 46% of patients who developed COVID-19 within 60 days of transplantation died. Acute kidney injury was common, and mycophenolate was discontinued in most patients. Conclusion Given the rapid global spread of COVID-19, reliable evidence is needed to inform public health policies. Hospitalised kidney transplant recipients with COVID-19 are at a high risk of death in early reports but interpretation of this data requires caution as studies were susceptible to period effects. Reassuringly, the quality of observational data is improving. Detailed and comprehensive data collection through linked registries will be necessary to conduct accurate analyses of risk factors for adverse outcomes, not least given the risks of stopping immunosuppression. This report highlights the early mortality excess in transplant recipients but medium and longer-term outcomes remain uncertain and merit careful investigation.
Objectives To assess the reporting and methodological quality of COVID-19 systematic reviews, and to analyze trends and gaps in the quality, clinical topics, author countries, and populations of the reviews using an evidence mapping approach. Study Design and Setting A structured search for systematic reviews concerning COVID-19 was performed using PubMed, Embase, Cochrane Library, Campbell Library, Web of Science, CBM, WanFang Data, CNKI, and CQVIP from inception until June 2020. The quality of each review was assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) checklist and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Results In total, 243 systematic reviews met the inclusion criteria, over 50% of which (128, 52.7%) were from 14 developing countries, with China contributing the most reviews (76, 31.3%). In terms of methodological quality of the studies, 30 (12.3%) were of moderate quality, 63 (25.9%) were of low quality, and 150 (61.7%) were of critically low quality. In terms of reporting quality, the median (interquartile range) PRISMA score was 14 (10–18). Regarding the topics of the reviews, 24 (9.9%) focused on the prevalence of COVID-19, 69 (28.4%) focused on the clinical manifestations, 30 (12.3%) focused on etiology, 43 (17.7%) focused on diagnosis, 65 (26.7%) focused on treatment, 104 (42.8%) focused on prognosis, and 25 (10.3%) focused on prevention. These studies mainly focused on general patients with COVID-19 (161, 66.3%), followed by children (22, 9.1%) and pregnant patients (18, 7.4%). Conclusion This study systematically evaluated the methodological and reporting quality of systematic reviews of COVID-19, summarizing and analyzing trends in their clinical topics, author countries, and study populations.
ObjectiveTo determine, in critically ill patients, the relative impact of proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), sucralfate, or no gastrointestinal bleeding prophylaxis (or stress ulcer prophylaxis) on outcomes important to patients.DesignSystematic review and network meta-analysis.Data sourcesMedline, PubMed, Embase, Cochrane Central Register of Controlled Trials, trial registers, and grey literature up to March 2019.Eligibility criteria for selecting studies and methodsWe included randomised controlled trials that compared gastrointestinal bleeding prophylaxis with PPIs, H2RAs, or sucralfate versus one another or placebo or no prophylaxis in adult critically ill patients. Two reviewers independently screened studies for eligibility, extracted data, and assessed risk of bias. A parallel guideline committee (BMJ Rapid Recommendation) provided critical oversight of the systematic review, including identifying outcomes important to patients. We performed random-effects pairwise and network meta-analyses and used GRADE to assess certainty of evidence for each outcome. When results differed between low risk and high risk of bias studies, we used the former as best estimates.ResultsSeventy two trials including 12 660 patients proved eligible. For patients at highest risk (>8%) or high risk (4-8%) of bleeding, both PPIs and H2RAs probably reduce clinically important gastrointestinal bleeding compared with placebo or no prophylaxis (odds ratio for PPIs 0.61 (95% confidence interval 0.42 to 0.89), 3.3% fewer for highest risk and 2.3% fewer for high risk patients, moderate certainty; odds ratio for H2RAs 0.46 (0.27 to 0.79), 4.6% fewer for highest risk and 3.1% fewer for high risk patients, moderate certainty). Both may increase the risk of pneumonia compared with no prophylaxis (odds ratio for PPIs 1.39 (0.98 to 2.10), 5.0% more, low certainty; odds ratio for H2RAs 1.26 (0.89 to 1.85), 3.4% more, low certainty). It is likely that neither affect mortality (PPIs 1.06 (0.90 to 1.28), 1.3% more, moderate certainty; H2RAs 0.96 (0.79 to 1.19), 0.9% fewer, moderate certainty). Otherwise, results provided no support for any affect on mortality, Clostridium difficile infection, length of intensive care stay, length of hospital stay, or duration of mechanical ventilation (varying certainty of evidence).ConclusionsFor higher risk critically ill patients, PPIs and H2RAs likely result in important reductions in gastrointestinal bleeding compared with no prophylaxis; for patients at low risk, the reduction in bleeding may be unimportant. Both PPIs and H2RAs may result in important increases in pneumonia. Variable quality evidence suggested no important effects of interventions on mortality or other in-hospital morbidity outcomes.Systematic review registrationPROSPERO CRD42019126656.
Background Dignity is a vitally important aspect of the lives of advanced cancer patients. We conducted a systematic review and meta‐analysis of the effectiveness of dignity therapy in this patient population. Methods We searched for randomized controlled trials comparing dignity therapy versus standard care for patients with advanced cancer in five comprehensive databases (March 2019), two clinical trial registries and one gray literature database (August 2019). The quality of the studies was assessed using the risk of bias tool recommended by the Cochrane Handbook Version 5.1.0. We used GRADE approach to assess the certainty of evidence. Meta‐analysis was performed with RevMan version 5.3. Outcomes of interest included anxiety, depression, dignity‐related distress and quality of life (QoL). Results Ten trials evaluating 904 patients (control, 449; experimental, 455) were identified. Six trials included patients with different types of advanced cancer, and four trials included patients with a single advanced cancer (lung cancer [20%], breast cancer [10%], and hepatocellular carcinoma [10%]). Compared with the standard care, dignity therapy decreased the score of anxiety, depression, and dignity‐related distress of the advanced cancer patients (SMD = −1.07, 95% CI: [−1.57, −0.58], p < .05; SMD = −1.31, 95% CI: [−1.92, −0.70], p < .05; MD = −7.30, 95% CI: [− 12.04, − 2.56], p < .05). In addition, no significant differences were found in the patient's QoL (p > .05). Conclusion Very low certainty evidence demonstrated that dignity therapy might be a promising treatment, especially in reducing anxiety and depression in advanced cancer patients.
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