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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The best way to quantitate venous reflux is still a matter of debate. Duplex-derived valve closure time (VCTs) have been used recently because they can be measured easily. We examined the relationships between VCT and duplex-obtained quantitation of venous volume and between VCT and air plethysmography (APG). Sixty-nine legs in 45 patients with varying clinical degrees of chronic venous insufficiency were studied by duplex scan and APG. VCTs were compared with duplex-derived flow calculations and with APG-derived venous filling index and residual volume fraction. The patient's mean age was 47.5 +/- 13.9 years; the mean duration of their symptoms was 13 +/- 4 years. Twenty percent had a history of deep venous thrombosis, and 29% had undergone venous surgery. No correlation was found between VCT and flow volume or between VCT and flow at peak reflux at any of the anatomic locations studied: saphenofemoral junction, greater saphenous vein, lesser saphenous vein, superficial femoral vein, profunda femoris vein, and popliteal vein. Likewise, no correlation was found between total VCT and APG-derived venous filling index or between total flow volumes and APG-derived residual volume fraction. Total VCT and total flow volumes did, however, have a moderate correlation (r = 0.65; p = 0.0003). Duplex-derived VCTs, although extremely useful in determining the presence of reflux, do not correlate with the magnitude of reflux, and should not be used to quantitate the degree of reflux.