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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Background Although pain management after total knee arthroplasty (TKA) affects rehabilitation, length of stay, and functional outcomes, pain management for patients undergoing TKA has yet to be standardized. Femoral nerve blocks (FNBs) are commonly used as an adjunct; however, these can result in transient quadriceps weakness and have been associated with in-hospital falls. Periarticular infiltration of liposomal bupivacaine has been recently introduced as a long-acting analgesic that can be administered without affecting motor function. Questions/purposes (1) Does periarticular liposomal bupivacaine compared with FNB result in improved pain control as measured by pain scores and narcotic consumption? (2) How do liposomal bupivacaine and FNB compare in terms of gait and stairclimbing milestones and the proportion of patients who experienced a fall in the hospital?Methods Between September 2013 and October 2014, a retrospective analysis was conducted involving 24 surgeons who performed a total of 1373 unilateral, primary TKAs. From September 2013 to April 2014, the routine approach to TKA pain management pathway consisted of preoperative administration of oral analgesics, intraoperative anesthesia (preferred spinal or general), an ultrasound-guided FNB, intraoperative analgesic cocktail injection, patient-controlled analgesia, and oral and IV narcotics for pain as needed. A total of 583 patients were included in this study group. Starting May 2014, FNBs were discouraged and there was department-wide adoption of liposomal bupivacaine. Liposomal bupivacaine became routinely used in all patients undergoing TKA with no other changes made to the multimodal analgesia protocol at that time, and 527 patients in this study group were compared with the FNB cohort. Chart review on a total of 1110 patients was conducted by a research assistant who was not participating in patient care. During the inpatient stay, pain scores during 8-hour intervals, narcotic use, and physical therapy milestones were compared. Results With the numbers available, we detected no clinically important difference in pain scores throughout the hospital stay; however, patients treated with liposomal bupivacaine consumed very slightly less narcotics overall (96 ± 62 versus 84 ± 73 eq mg of morphine; [95% confidence interval, 11-13 mg]; p = 0. Conclusions In the absence of strong data supporting FNB over liposomal bupivacaine, we have modified our TKA pain management protocols by adopting liposomal bupivacaine in lieu of FNBs, facilitating rapid rehabilitation while providing adequate pain control. Level of Evidence Level III, therapeutic study.