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.

Objective Randomized comparisons of acceptance-based treatments with traditional cognitive behavioral therapy (CBT) for anxiety disorders are lacking. To address this research gap, we compared acceptance and commitment therapy (ACT) to CBT for heterogeneous anxiety disorders. Method One hundred twenty eight individuals (52% female, mean age = 38, 33% minority) with one or more DSM-IV anxiety disorders began treatment following randomization to 12 sessions of CBT or ACT; both treatments included behavioral exposure. Assessments at pre-treatment, post-treatment, 6-month, and 12-month follow-up measured anxiety specific (principal disorder Clinical Severity Ratings [CSR], Anxiety Sensitivity Index, Penn State Worry Questionnaire, Fear Questionnaire avoidance) and non-anxiety specific (Quality of Life Index [QOLI], Acceptance and Action Questionnaire-16 [AAQ]) outcomes. Treatment adherence and therapist competency ratings, treatment credibility, and co-occurring mood and anxiety disorders were investigated. Results CBT and ACT improved similarly across all outcomes from pre- to post-treatment. During follow-up, ACT showed steeper CSR improvements than CBT (p < .05, d = 1.33) and at 12-month follow-up, ACT showed lower CSRs than CBT among completers (p < .05, d = 1.05). At 12-month follow-up, ACT reported higher AAQ than CBT (p = .08, d = .42; Completers: p < .05, d = .59) whereas CBT reported higher QOLI than ACT (p < .05, d = .43). Attrition and comorbidity improvements were similar, although ACT utilized more non-study psychotherapy at 6-month follow-up. Therapist adherence and competency were good; treatment credibility was higher in CBT. Conclusions Overall improvement was similar between ACT and CBT, indicating that ACT is a highly viable treatment for anxiety disorders.

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The present research suggests that although treatment expectation and homework compliance likely represent unique constructs of treatment engagement, homework compliance may be the more important treatment engagement variable for outcomes. The present research suggests that improvement of homework compliance has the potential to be a highly practical and effective way to improve clinical outcomes in CBT targeting anxiety disorders.

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Although threat unpredictability plays an important role in determining emotional responses, little is known about what elements of unpredictability are responsible for these results. The current study examined the single and combined effects of two elements of unpredictable threat: (a) uncertainty about the timing of an aversive event (temporal unpredictability), and (b) uncertainty about whether an aversive event will occur at all (cue unpredictability). Seventy-two healthy young adult participants were randomly assigned to receive either temporally predictable or unpredictable shocks at varying levels of cue unpredictability. Dependent variables included skin conductance responses (SCRs) and eyeblink startle reflex. Combined cue and temporal unpredictability elicited weaker SCRs than either element of unpredictability alone, indicating that high unpredictability may induce anxiety-like physiological inhibition. Combined cue and temporal unpredictability and combined cue and temporal predictability produced the largest startle. Findings provide evidence that both cue and temporal unpredictability should be included in human models of anxiety.