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— Therapeutic hypothermia is recommended for the treatment of neurological injury after resuscitation from out-of-hospital cardiac arrest. Laboratory studies have suggested that earlier cooling may be associated with improved neurological outcomes. We hypothesized that induction of therapeutic hypothermia by paramedics before hospital arrival would improve outcome. Methods and Results— In a prospective, randomized controlled trial, we assigned adults who had been resuscitated from out-of-hospital cardiac arrest with an initial cardiac rhythm of ventricular fibrillation to either prehospital cooling with a rapid infusion of 2 L of ice-cold lactated Ringer’s solution or cooling after hospital admission. The primary outcome measure was functional status at hospital discharge, with a favorable outcome defined as discharge either to home or to a rehabilitation facility. A total of 234 patients were randomly assigned to either paramedic cooling (118 patients) or hospital cooling (116 patients). Patients allocated to paramedic cooling received a median of 1900 mL (first quartile 1000 mL, third quartile 2000 mL) of ice-cold fluid. This resulted in a mean decrease in core temperature of 0.8°C ( P =0.01). In the paramedic-cooled group, 47.5% patients had a favorable outcome at hospital discharge compared with 52.6% in the hospital-cooled group (risk ratio 0.90, 95% confidence interval 0.70 to 1.17, P =0.43). Conclusions— In adults who have been resuscitated from out-of-hospital cardiac arrest with an initial cardiac rhythm of ventricular fibrillation, paramedic cooling with a rapid infusion of large-volume, ice-cold intravenous fluid decreased core temperature at hospital arrival but was not shown to improve outcome at hospital discharge compared with cooling commenced in the hospital. Clinical Trial Registration— URL: http://www.anzctr.org.au. Unique identifier: ACTRN12605000179639.

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Great emphasis is placed on educating asthmatics to use action plans to achieve better control of symptoms. The use of peak flow meters (PFM) has been recommended as an important part of self-management plans. We studied 92 (47 F) adult patients with asthma in a primary care setting to compare the effectiveness of action plans using either peak flow monitoring or symptoms to guide self-management. Each patient was instructed in the use of the action plan in the context of a 6-mo asthma education program taught by a nurse. Patients were already using inhaled corticosteroids or were newly prescribed corticosteroids by their family physician. Forty-four patients were randomized to the PFM group and 48 to the symptoms group. Spirometry, symptom scores, quality of life, medication use, and measures of health care utilization and morbidity (emergency department visits, hospitalizations, unscheduled doctor visits, and days lost from work or school) were recorded at baseline and throughout the study period. PC20 methacholine was measured at the first and at the final visits. There were significant improvements within groups for FEV1, symptoms score, PC20 methacholine, and quality of life, but no between-group differences. A significant shift from higher to lower daily use of beta-agonists (p < 0.008 for both groups) and significant shifts to higher daily doses of inhaled steroids (p < 0.001) occurred in each group. Adherence to the self-management plans was only 65% in the PFM group and 52% in the symptoms group. Outcomes for health care utilization were similar except for fewer patients making unscheduled doctor visits within the PFM group. Our findings show that education, regular follow-up, and an action plan are effective in improving asthma control and quality of life, but the routine use of PFM to guide interventions is not the only way to accomplish these objectives.

ObjectiveEarly warning scores (EWS) are used to predict patient outcomes. We aimed to determine which of 13 EWS, based largely on emergency department (ED) vital sign data, best predict important clinical outcomes.MethodWe undertook a prospective cohort study in a metropolitan, tertiary-referral ED in Melbourne, Australia (February–April 2018). Patient demographics, vital signs and management data were collected while the patients were in the ED and EWS were calculated using each EWS criteria. Outcome data were extracted from the medical record (2-day, 7-day and 28-day inhospital mortality, clinical deterioration within 2 days, intensive care unit (ICU) admission within 2 days, admission to hospital). Area under the receiver operator characteristic (AUROC; 95% CIs) curves were used to evaluate the predictive ability of each EWS for each outcome.ResultsOf 1730 patients enrolled, 690 patients were admitted to the study hospital. Most EWS were good or excellent predictors of 2-day mortality. When considering the point estimates, the VitalPac EWS was the most strongly predictive (AUROC: 0.96; 95% CI: 0.92 to 0.99). However, when considering the 95% CIs, there was no significant difference between the highest performing EWS. The predictive ability for 7-day and 28-day mortality was generally less. No EWS was a good predictor for clinical deterioration (AUROC range: 0.54–0.70), ICU admission (range: 0.51–0.72) or admission to hospital (range: 0.51–0.68).ConclusionSeveral EWS have excellent predictive ability for 2-day mortality and have the potential to risk stratify patients in ED. No EWS adequately predicted clinical deterioration, admission to either ICU or the hospital.

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