Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

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ContextGastroenteritis remains a leading cause of childhood morbidity.ObjectiveBecause prior reviews have focused on isolated symptoms and studies conducted in developing countries, this study focused on interventions commonly considered for use in developed countries. Intervention specific, patient-centered outcomes were selected.Data SourcesMEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, trial registries, grey literature, and scientific meetings.Study SelectionRandomized controlled trials, conducted in developed countries, of children aged <18 years, with gastroenteritis, performed in emergency department or outpatient settings which evaluated oral rehydration therapy (ORT), antiemetics, probiotics or intravenous fluid administration rate.Data ExtractionThe study was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. Data were independently extracted by multiple investigators. Analyses employed random effects models.Results31 trials (4,444 patients) were included. ORT: Compared with intravenous rehydration, hospitalization (RR 0.80, 95%CI 0.24, 2.71) and emergency department return visits (RR 0.86, 95%CI 0.39, 1.89) were similar. Antiemetics: Fewer children administered an antiemetic required intravenous rehydration (RR 0.40, 95%CI 0.26, 0.60) While the data could not be meta-analyzed, three studies reported that ondansetron administration does increase the frequency of diarrhea. Probiotics: No studies reported on the primary outcome, three studies evaluated hospitalization within 7 days (RR 0.87, 95%CI 0.25, 2.98). Rehydration: No difference in length of stay was identified for rapid vs. standard intravenous or nasogastric rehydration. A single study found that 5% dextrose in normal saline reduced hospitalizations compared with normal saline alone (RR 0.70, 95% CI 0.53, 0.92).ConclusionsThere is a paucity of patient-centered outcome evidence to support many interventions. Since ORT is a low-cost, non-invasive intervention, it should continue to be used. Routine probiotic use cannot be endorsed at this time in outpatient children with gastroenteritis. Despite some evidence that ondansetron administration increases diarrhea frequency, emergency department use leads to reductions in intravenous rehydration and hospitalization. No benefits were associated with ondansetron use following emergency department discharge.