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.
Background Despite exacerbations of chronic obstructive pulmonary disease (COPD) being both common and often fatal, accurate prognostication of patients hospitalised with an exacerbation is difficult. For exacerbations complicated by pneumonia, the CURB-65 prognostic tool is frequently used but its use in this population is suboptimal. Methods Consecutive patients hospitalised with an exacerbation of COPD were recruited. Admission clinical data and inhospital death rates were recorded. Independent predictors of outcome were identified by logistic regression analysis and incorporated into a clinical prediction tool. Results 920 patients were recruited: mean (SD) age was 73.1 (10.0) years; 53.9% were female subjects; mean (SD) forced expiratory volume in one second was 43.6 (17.2) % predicted; and 96 patients (10.4%) died in hospital. The five strongest predictors of mortality (extended MRC Dyspnoea Score, eosinopenia, consolidation, acidaemia, and atrial fibrillation) were combined to form the Dyspnoea, Eosinopenia, Consolidation, Acidaemia and atrial Fibrillation (DECAF) Score. The Score, which underwent internal bootstrap validation, showed excellent discrimination for mortality (area under the receiver operator characteristic curve ¼0.86, 95% CI 0.82 to 0.89) and performed more strongly than other clinical prediction tools. In the subgroup of patients with coexistent pneumonia (n¼299), DECAF was a significantly stronger predictor of mortality than CURB-65. Conclusions The DECAF Score is a simple yet effective predictor of mortality in patients hospitalised with an exacerbation of COPD and has the potential to help clinicians more accurately predict prognosis, and triage place and level of care to improve outcome in this common condition.
Background Rates of mortality and readmission are high in patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). In this population, the prognostic value of the Medical Research Council Dyspnoea Scale (MRCD) is uncertain, and an extended MRCD (eMRCD) scale has been proposed to improve its utility. Coexistent pneumonia is common and, although the CURB-65 prediction tool is used, its discriminatory value has not been reported. Methods Clinical and demographic data were collected on consecutive patients hospitalised with AECOPD. The relationship of stable-state dyspnoea severity to inhospital mortality and 28-day readmission was assessed. The discriminatory value of CURB-65, MRCD and eMRCD, in the prediction of in-hospital mortality, was assessed and compared. Results 920 patients were recruited. 10.4% died inhospital and 19.1% of the 824 survivors were readmitted within 28 days of discharge. During their stable state prior to admission, 34.2% of patients were too breathless to leave the house. Mortality was significantly higher in pneumonic than in non-pneumonic exacerbations (20.1% vs 5.8%, p<0.001). eMRCD was a significantly better discriminator than either CURB-65 or the traditional MRCD scale for predicting in-hospital mortality, and was a stronger prognostic tool than CURB-65 in the subgroup of patients with pneumonic AECOPD. Conclusions The severity of dyspnoea in the stable state predicts important clinical outcomes in patients hospitalised with AECOPD. The eMRCD scale identifies a subgroup of patients at a particularly high risk of inhospital mortality and is a better predictor of mortality risk than CURB-65 in exacerbations complicated by pneumonia. BACKGROUND
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