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Drug treatments for covid-19: living systematic review and network meta-analysis
OBJECTIVE To compare the effects of treatments for coronavirus disease 2019 (covid-19). DESIGN Living systematic review and network meta-analysis. DATA SOURCES US 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 SELECTION Randomised 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. METHODS After 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. RESULTS 23 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. CONCLUSION Glucocorticoids 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.
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Comparative effectiveness of transitional care services in patients discharged from the hospital with heart failure: A systematic review and network meta-analysis
Aims: To compare the effectiveness of transitional care services in decreasing all-cause death and all-cause readmissions following hospitalization for heart failure (HF). Methods and results: We searched PubMed, Embase, CINAHL, and Cochrane Clinical Trials Register for randomized controlled trials (RCTs) published in 2000-2015 that tested the efficacy of transitional care services in patients hospitalized for HF, provided ≥1 month of follow-up, and reported all-cause mortality or all-cause readmissions. Our network meta-analysis included 53 RCTs (12 356 patients). Among services that significantly decreased all-cause mortality compared with usual care, nurse home visits were most effective [ranking P-score 0.6794; relative risk (RR) 0.78, 95% confidence intervals (CI) 0.62-0.98], followed by disease management clinics (DMCs) (ranking P-score 0.6368; RR 0.80, 95% CI 0.67-0.97). Among services that significantly decreased all-cause readmission, nurse home visits were most effective [ranking P-score 0.8365; incident rate ratio (IRR) 0.65, 95% CI 0.49-0.86], followed by nurse case management (NCM) (ranking P-score 0.6168; IRR 0.77, 95% CI 0.63-0.95), and DMCs (ranking P-score 0.5691; IRR 0.80, 95% CI 0.66-0.97). There was no significant difference in the comparative effectiveness of services that improved each outcome. Nurse home visits had the greatest pooled cost-savings (3810 USD, 95% CI 3682-3937), followed by NCM (3435 USD, 95% CI 3224-3645), and DMCs (245 USD, 95% CI -70 to 559). Telephone, telemonitoring, pharmacist, and education interventions did not significantly improve clinical outcomes. Conclusion: Nurse home visits and DMCs decrease all-cause mortality after hospitalization for HF. Along with NCM, they also reduce all-cause readmissions, with no significant difference in comparative effectiveness. These services reduce healthcare system costs to varying degrees.
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