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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Recent U.S. Supreme Court opinions regarding extended sentencing for juveniles have made reference to their immaturity on the basis of what any parent knows (Roper v. Simmons, 2005) and to evidence from psychology and brain science indicating differences in brain processes underlying control of behavior, making juveniles more vulnerable to impulsivity and risk taking. Society as whole, but parents in particular, recognize the teen years as a period marked by significant changes in behavior, characterized by sensation seeking, defiance, and emotional outbursts. As teens begin to make independent decisions, their choices can, at times, seem ill conceived, putting themselves and others in danger. Teenagers are in the throes of adolescence, the transitional period marked by the beginning of puberty and extending through the late teens and into the early 20s. Recent neuroscience research has provided evidence of specific immaturities in brain processes that offer new insights into possible constraints in decision-making abilities in adolescence. Specifically, advances in noninvasive neuroimaging methods have allowed researchers to quantify changes in brain structure and function throughout adolescence and into adulthood, helping to identify processes that underlie decision making. These findings have implications for juvenile law specific to adolescents as a unique group of individuals that warrant careful interpretation.Behaviorally, adolescence is a period of heightened propensity for novelty and sensation seeking and is present across cultures and species (Spear, 2010). This increase in sensation seeking is believed to be primarily an adaptive process crucial for gaining skills that support independent trajectories as adults (Casey et al., 2010). Sensation seeking is marked by the pursuit of thrills, adventure, and experience as well as disinhibition and susceptibility to boredom. Sensation seeking, however, can lead to risk-taking behaviors, which can undermine survival. Risk-taking behaviors are defined by having a high-perceived reward value but known potential negative consequences, which are undervalued to pursue thrills. Typical risk-taking behaviors can range from extreme sports to substance abuse and criminal behavior. Research has indicated that adolescents have a heightened sensitivity to the potential rewards of risk taking, as well as increased sensitivity to peer influence (when compared with adults), making them particularly vulnerable to risk taking (Gardner & Steinberg, 2005).Risk taking involves decision making and planning but, also important, heightened motivation driven by impulsive behavior. During the adolescent period, there is a particular relationship between a newly gained ability to plan and make decisions similar to adults but in the context of still immature impulse control and heightened sensitivity to rewards. These behavioral differences occur in parallel to neurobiological specialization in brain systems that support executive control and motivation. The physical and behavioral dist...