IMPORTANCE: Convalescent plasma is a proposed treatment for COVID-19. OBJECTIVE: To assess clinical outcomes with convalescent plasma treatment vs placebo or standard of care in peer-reviewed and ...preprint publications or press releases of randomized clinical trials (RCTs). DATA SOURCES: PubMed, the Cochrane COVID-19 trial registry, and the Living Overview of Evidence platform were searched until January 29, 2021. STUDY SELECTION: The RCTs selected compared any type of convalescent plasma vs placebo or standard of care for patients with confirmed or suspected COVID-19 in any treatment setting. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data on relevant clinical outcomes, trial characteristics, and patient characteristics and used the Cochrane Risk of Bias Assessment Tool. The primary analysis included peer-reviewed publications of RCTs only, whereas the secondary analysis included all publicly available RCT data (peer-reviewed publications, preprints, and press releases). Inverse variance–weighted meta-analyses were conducted to summarize the treatment effects. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation. MAIN OUTCOMES AND MEASURES: All-cause mortality, length of hospital stay, clinical improvement, clinical deterioration, mechanical ventilation use, and serious adverse events. RESULTS: A total of 1060 patients from 4 peer-reviewed RCTs and 10 722 patients from 6 other publicly available RCTs were included. The summary risk ratio (RR) for all-cause mortality with convalescent plasma in the 4 peer-reviewed RCTs was 0.93 (95% CI, 0.63 to 1.38), the absolute risk difference was −1.21% (95% CI, −5.29% to 2.88%), and there was low certainty of the evidence due to imprecision. Across all 10 RCTs, the summary RR was 1.02 (95% CI, 0.92 to 1.12) and there was moderate certainty of the evidence due to inclusion of unpublished data. Among the peer-reviewed RCTs, the summary hazard ratio was 1.17 (95% CI, 0.07 to 20.34) for length of hospital stay, the summary RR was 0.76 (95% CI, 0.20 to 2.87) for mechanical ventilation use (the absolute risk difference for mechanical ventilation use was −2.56% 95% CI, −13.16% to 8.05%), and there was low certainty of the evidence due to imprecision for both outcomes. Limited data on clinical improvement, clinical deterioration, and serious adverse events showed no significant differences. CONCLUSIONS AND RELEVANCE: Treatment with convalescent plasma compared with placebo or standard of care was not significantly associated with a decrease in all-cause mortality or with any benefit for other clinical outcomes. The certainty of the evidence was low to moderate for all-cause mortality and low for other outcomes.
Assessing changes in coverage, recall, review, conclusions and references not found when searching fewer databases.
In randomly selected 60 Cochrane reviews, we checked included study publications' ...coverage (indexation) and recall (findability) using different search approaches with MEDLINE, Embase, and CENTRAL and related them to authors' conclusions and certainty. We assessed characteristics of unfound references.
Overall 1989/2080 included references, were indexed in ≥1 database (coverage = 96%). In reviews where using one of our search approaches would not change conclusions and certainty (n = 44-54), median coverage and recall were highest (range 87.9%-100.0% and 78.2%-93.3%, respectively). Here, searching ≥2 databases reached >95% coverage and ≥87.9% recall. In reviews with unchanged conclusions but less certainty (n = 2-8): 63.3%-79.3% coverage and 45.0%-75.0% recall. In reviews with opposite conclusions (n = 1-3): 63.3%-96.6% and 52.1%-78.7%. In reviews where a conclusion was no longer possible (n = 3-7): 60.6%-86.0% and 20.0%-53.8%. The 265 references that were indexed but unfound were more often abstractless (30% vs. 11%) and older (28% vs. 17% published before 1991) than found references.
Searching ≥2 databases improves coverage and recall and decreases the risk of missing eligible studies. If researchers suspect that relevant articles are difficult to find, supplementary search methods should be used.
Subacute cough following a non-specific viral infection lasting 3-8 weeks is common. However, despite many treatment options there are no systematic reviews evaluating these.
To provide a systematic ...overview of treatment options and outcomes evaluated in randomised clinical trials (RCTs).
Systematic review and meta-analyses assessing the overall effects of any treatment for subacute cough.
The authors systematically searched PubMed/MEDLINE and the Cochrane Central Register of Controlled Trials (last search March 2017) for RCTs in adult patients with subacute cough. The authors considered trials evaluating any outcome of any drug or non-drug treatments, apart from traditional Chinese and Asian medicines. They combined treatment effects on cough-related outcomes in random effects meta-analyses.
Six eligible RCTs including 724 patients were identified. These assessed montelukast, salbutamol plus ipratropium bromide, gelatine, fluticasone propionate, budesonide, and nociception opioid 1 receptor agonist and codeine. Five studies reported effects on various cough severity scores at various timepoints. No treatment option was associated with a clear benefit on cough recovery or other patient-relevant outcomes in any of the studies or in meta-analyses for cough outcomes at 14 days and 28 days. Reported adverse events were rather mild and reported for 14% of patients across all treatments.
Evidence on treatment options for subacute cough is weak. There is no treatment showing clear patient-relevant benefits in clinical trials.
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