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 Maintenance hemodialysis is typically prescribed thrice-weekly irrespective of patient's residual kidney function (RKF). We hypothesized that a less frequent schedule at hemodialysis initiation is associated with greater preservation of RKF without compromising survival among patients with substantial RKF. Study Design A longitudinal cohort Setting & Participants 23,645 patients who initiated maintenance hemodialysis in a large dialysis organization in the United States (1/2007–12/2010), who had available RKF data during the first 91 days (or quarter) of dialysis, and who survived the first year. Predictor Incremental (routine twice-weekly for >6 continuous weeks during the first 91 days upon transition to dialysis) versus conventional (thrice-weekly) hemodialysis regimens during the same time. Outcomes Changes in renal urea clearance (KRU) and urine volume (UV) during one year after the first quarter, and survival after the first year. Results Among 23,645 included patients, 51% had substantial KRU (≥3.0 mL/min/1.73m2) at baseline. Compared to 8,068 patients with conventional hemodialysis regimen matched based on baseline KRU, UV, age, gender, diabetes, and central venous catheter use, 351 patients with incremental regimen exhibited 16% (95% CI, 5%-28%) and 15% (95% CI, 2%-30%) more preserved KRU and UV at second quarter, respectively, which remained across the following quarters. Incremental regimen showed higher mortality risk in patients with inadequate baseline KRU (≤3.0 mL/min/1.73m2; HR, 1.61; 95% CI, 1.07-2.44), but not in those with higher baseline KRU (HR, 0.99; 95% CI, 0.76-1.28). Results were similar in subgroup defined by baseline UV of 600 mL/day. Limitations Potential selection bias and wide CIs. Conclusions Among incident hemodialysis patients with substantial RKF, incremental hemodialysis may be a safe treatment regimen and associated with greater preservation of RKF while higher mortality is observed after a year in those with lowest RKF. Clinical trials are needed to examine safety and effectiveness of twice-weekly hemodialysis.
These results suggest that an elevated pre-operative BNP or NT-proBNP measurement is a powerful, independent predictor of cardiovascular events in the first 30 days after noncardiac surgery.
In patients with ESRD, residual kidney function (RKF) contributes to achievement of adequate solute clearance. However, few studies have examined RKF in patients on hemodialysis. In a longitudinal cohort of 6538 patients who started maintenance hemodialysis over a 4-year period (January 2007 through December 2010) and had available renal urea clearance (CL) data at baseline and 1 year after hemodialysis initiation, we examined the association of annual change in renal CL rate with subsequent survival. The median (interquartile range) baseline value and mean±SD annual change of CL were 3.3 (1.9-5.0) and -1.1±2.8 ml/min per 1.73 m, respectively. Greater CL rate 1 year after hemodialysis initiation associated with better survival. Furthermore, we found a gradient association between loss of RKF and all-cause mortality: changes in CL rate of -6.0 and +3.0 ml/min per 1.73 m per year associated with case mix-adjusted hazard ratios (95% confidence intervals) of 2.00 (1.55 to 2.59) and 0. 61 (0.50 to 0.74), respectively (reference: -1.5 ml/min per 1.73 m per year). These associations remained robust against adjustment for laboratory variables and ultrafiltration rate and were consistent across strata of baseline CL, age, sex, race, diabetes status, presence of congestive heart failure, and hemoglobin, serum albumin, and serum phosphorus levels. Sensitivity analyses using urine volume as another index of RKF yielded consistent associations. In conclusion, RKF decline during the first year of dialysis has a graded association with all-cause mortality among incident hemodialysis patients. The clinical benefits of RKF preservation strategies on mortality should be determined.
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