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.

Survey research is an important form of scientific inquiry 1 that merits rigorous design and analysis. 2 The aim of a survey is to gather reliable and unbiased data from a representative sample of respondents.3 Increasingly, investigators administer questionnaires to clinicians about their knowledge, attitudes and practice 2,4,5 to generate or refine research questions and to evaluate the impact of clinical research on practice. Questionnaires can be descriptive (reporting factual data) or explanatory (drawing inferences between constructs or concepts) and can explore several constructs at a time. Questionnaires can be informal, conducted as preparatory work for future studies, or formal, with specific objectives and outcomes.Rigorous questionnaires can be challenging and labour-intensive to develop, test and administer without the help of a systematic approach. 5 In this article, we outline steps to design, develop, test and administer valid questionnaires with minimal bias and optimal response rates. We focus on selfadministered postal and electronic surveys of clinicians that are amenable to quantitative analysis. We highlight differences between postal and electronic administration of surveys and review strategies that enhance response rates and reporting transparency. Although intended to assist in the conduct of rigorous self-administered surveys, our article may also help clinicians in the appraisal of published surveys.

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Objective To review the literature on the use of inhaled nitric oxide to treat acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and to summarise the effects of nitric oxide, compared with placebo or usual care without nitric oxide, in adults and children with ALI or ARDS. Design Systematic review and meta-analysis.

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Objective To compare quality of care in for-profit and notfor-profit nursing homes. Design Systematic review and meta-analysis of observational studies and randomised controlled trials investigating quality of care in for-profit versus not-forprofit nursing homes. Results A comprehensive search yielded 8827 citations, of which 956 were judged appropriate for full text review. Study characteristics and results of 82 articles that met inclusion criteria were summarised, and results for the four most frequently reported quality measures were pooled. Included studies reported results dating from 1965 to 2003. In 40 studies, all statistically significant comparisons (P<0.05) favoured not-for-profit facilities; in three studies, all statistically significant comparisons favoured for-profit facilities, and the remaining studies had less consistent findings. Meta-analyses suggested that not-for-profit facilities delivered higher quality care than did for-profit facilities for two of the four most frequently reported quality measures: more or higher quality staffing (ratio of effect 1.11, 95% confidence interval 1.07 to 1.14, P<0.001) and lower pressure ulcer prevalence (odds ratio 0.91, 95% confidence interval 0.83 to 0.98, P=0.02). Non-significant results favouring not-for-profit homes were found for the two other most frequently used measures: physical restraint use (odds ratio 0.93, 0.82 to 1.05, P=0.25) and fewer deficiencies in governmental regulatory assessments (ratio of effect 0.90, 0.78 to 1.04, P=0.17). Conclusions This systematic review and meta-analysis of the evidence suggests that, on average, not-for-profit nursing homes deliver higher quality care than do for-profit nursing homes. Many factors may, however, influence this relation in the case of individual institutions. INTRODUCTIONNursing homes provide long term housing, support, and 24 hour nursing care for people who are unable

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In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. Patients were randomized to accelerated (12 h or less from eligibility) or standard RRT initiation. Outcomes were adherence to protocol-defined time windows for RRT initiation (primary), proportion of eligible patients enrolled, follow-up to 90 days, and safety in 101 fully eligible patients (57 with sepsis) with a mean age of 63 years. Median serum creatinine and urine output at enrollment were 268 micromoles/l and 356 ml per 24 h, respectively. In the accelerated arm, all patients commenced RRT and 45/48 did so within 12 h from eligibility (median 7.4 h). In the standard arm, 33 patients started RRT at a median of 31.6 h from eligibility, of which 19 did not receive RRT (6 died and 13 recovered kidney function). Clinical outcomes were available for all patients at 90 days following enrollment, with mortality 38% in the accelerated and 37% in the standard arm. Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial.