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.

No abstract

No abstract

No abstract

No abstract

No abstract

Acute ingestion of ketone salts induces nutritional ketosis by elevating β-hydroxybutyrate (βHB), but few studies have examined the metabolic effects of ingestion prior to exercise. Nineteen trained cyclists (12 male, 7 female) undertook graded exercise (8 min each at ∼30%, 40%, 50%, 60%, 70%, and 80% VO) on a cycle ergometer on two occasions separated by either 7 or 14 days. Trials included ingestion of boluses of either (i) plain water (3.8 mL kg body mass) (CON) or (ii) βHB salts (0.38 g kg body mass) in plain water (3.8 mL kg body mass) (KET), at both 60 min and 15 min prior to exercise. During KET, plasma [βHB] increased to 0.33 ± 0.16 mM prior to exercise and 0.44 ± 0.15 mM at the end of exercise (both p < .05). Plasma glucose was 0.44 ± 0.27 mM lower (p < .01) 30 min after ingestion of KET and remained ∼0.2 mM lower throughout exercise compared to CON (p < .001). Respiratory exchange ratio (RER) was higher during KET compared to CON (p < .001) and 0.03-0.04 higher from 30%VO to 60%VO (all p < .05). No differences in plasma lactate, rate of perceived exertion, or gross or delta efficiency were observed between trials. Gastrointestinal symptoms were reported in 13 out of 19 participants during KET. Acute ingestion of βHB salts induces nutritional ketosis and alters the metabolic response to exercise in trained cyclists. Elevated RER during KET may be indicative of increased ketone body oxidation during exercise, but at the plasma βHB concentrations achieved, ingestion of βHB salts does not affect lactate appearance, perceived exertion, or muscular efficiency.

There is no universally agreed set of anatomical structures that must be identified on ultrasound for the performance of ultrasound-guided regional anesthesia (UGRA) techniques. This study aimed to produce standardized recommendations for core (minimum) structures to identify during seven basic blocks. An international consensus was sought through a modified Delphi process. A long-list of anatomical structures was refined through serial review by key opinion leaders in UGRA. All rounds were conducted remotely and anonymously to facilitate equal contribution of each participant. Blocks were considered twice in each round: for “orientation scanning” (the dynamic process of acquiring the final view) and for the “block view” (which visualizes the block site and is maintained for needle insertion/injection). Strong recommendations for inclusion were made if ≥75% of participants rated a structure as “definitely include” in any round. Weak recommendations were made if >50% of participants rated a structure as “definitely include” or “probably include” for all rounds (but the criterion for “strong recommendation” was never met). Thirty-six participants (94.7%) completed all rounds. 128 structures were reviewed; a “strong recommendation” is made for 35 structures on orientation scanning and 28 for the block view. A “weak recommendation” is made for 36 and 20 structures, respectively. This study provides recommendations on the core (minimum) set of anatomical structures to identify during ultrasound scanning for seven basic blocks in UGRA. They are intended to support consistent practice, empower non-experts using basic UGRA techniques, and standardize teaching and research.