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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Internet-delivered cognitive behavioural therapy for post-traumatic stress disorder: systematic review and meta-analysis.Objective: To determine whether Internet-delivered cognitive behavioural therapy (i-CBT) is an effective treatment for those who meet diagnostic criteria for post-traumatic stress disorder (PTSD). Method: A systematic review was undertaken according to Cochrane Collaboration Guidelines. The primary outcome measures were reduction in PTSD symptoms and drop-out. Categorical outcomes were meta-analysed as risk ratios (RRs) and continuous outcomes as mean differences (MDs) or standardised mean differences (SMDs). Results: Ten studies with 720 participants were included. Evidence showed that i-CBT may be associated with a clinically important reduction in post-treatment PTSD symptoms compared with wait list (SMD À0.60, 95% confidence interval À0.97 to À0.24; N = 560); however, only three studies reported follow-up data, and there was no evidence to support the maintenance of symptom improvement at follow-up of 3-6 months. There was no evidence of a difference in PTSD symptoms between i-CBT and Internet-delivered non-CBT posttreatment. There was evidence of greater treatment effect from traumafocused i-CBT than i-CBT without a trauma focus, as well as evidence that treatment effect was increased by the provision of guidance. Conclusions: While the review found some beneficial effects of i-CBT for PTSD post-treatment, the quality of the evidence was very low because of the small number of included trials and there was insufficient evidence to support the maintenance of improvement at follow-up of 3-6 months. Further work is required to establish non-inferiority to current first-line interventions; to determine long-term efficacy; to explore mechanisms of effect; and to establish optimal levels of guidance. Summations• i-CBT may be associated with a clinically important reduction in PTSD symptoms post-treatment, but there is currently a lack of evidence to support maintenance of the effect at follow-up.• There was evidence of greater treatment effect from trauma-focused i-CBT than i-CBT without a trauma focus, as well as evidence that treatment effect was increased by the provision of guidance.• Further work is required to establish non-inferiority to current first-line interventions. Limitations• Only ten studies were eligible for inclusion, and sample sizes were often small. • Participants included in the ten studies were predominantly from the United States and Western Europe, employed and had relatively high levels of education. It is not possible to determine whether similar results would have been obtained from participants with more representative demographic characteristics.• There was a lack of independent evaluation. All but one of the programmes were evaluated by the programme developers themselves.