Background The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear. Methods We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses. Results We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P=0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P=0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P=0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo. Conclusions Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937 .)

The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group IMPORTANCE Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.OBJECTIVE To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.DATA SOURCES Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts.STUDY SELECTION Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria. DATA EXTRACTION AND SYNTHESISIn this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I 2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality. MAIN OUTCOMES AND MEASURESThe primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days.RESULTS A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P < .001) for tocilizumab and 1.08 (95% CI, 0.86-1.36; P = .52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68-0.87) for tocilizumab and 0.92 (95% CI, 0.61-1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16). CONCLUSIONS AND RELEVANCEIn this prospective meta-analysis of clinical trials of patients hosp...

The objective of the study is to determine the association between emergency department (ED) crowding and preventable medical errors (PME). This was a retrospective cohort study of 533 ED patients enrolled in the National ED Safety Study (NEDSS) in four Massachusetts EDs. Individual patients' average exposure to ED crowding during their ED visit was compared with the occurrence of a PME (yes/no) for the three diagnostic categories in NEDSS: acute myocardial infarction, asthma exacerbation, and dislocation requiring procedural sedation. To accommodate site-to-site differences in available administrative data, ED crowding was measured using one of three previously validated crowding metrics (ED Work Index, ED Workscore, and ED Occupancy). At each site, the continuous measure was placed into site-specific quartiles, and these quartiles then were combined across sites. We found that 46 (8.6%; 95% confidence interval, 6.4-11.3%) of the 533 patients experienced a PME. For those seen during higher levels of ED crowding (quartile 4 vs. quartile 1), the occurrence of PMEs was more than twofold higher, both on unadjusted analysis and adjusting for two potential confounders (diagnosis, site). The association appeared non-linear, with most PMEs occurring at the highest crowding level. We identified a direct association between high levels of ED crowding and risk of preventable medical errors. Further study is needed to determine the generalizability of these results. Should such research confirm our findings, we would suggest that mitigating ED crowding may reduce the occurrence of preventable medical errors.

The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701).

We conducted a 6-month open-label trial in which 10 patients with active psoriatic arthritis received 2 pg of oral 1,25-dihydroxyvitamin D3 daily. Statistically significant improvement was noted in the tender joint count and physician global impression. Of these 10 patients, 4 had substantial ( 2 5 0 % ) improvement, and 3 had moderate (225%) improvement in the tender joint count. Two patients were unable to receive therapeutic doses because of hypercalciuria. High-dose vitamin D may be a useful therapeutic agent for psoriatic arthritis.so, was there any correlation between improvement in the skin lesions and improvement in the arthritis. PATIENTS AND METHODS Patient selection criteria.Patients 18-70 years of age with active psoriatic arthritis were eligible for this study. They were recruited from the clinic populations of the Boston University Hospitals (University Hospital, Boston City Hospital, and Boston VA Medical Center) or were referred by rheumatologists in private The principal therapies used in psoriatic arthritis are nonsteroidal antiinflammatory drugs (NSAIDs), prednisone, and, in some cases, antimalarial agents, gold salts, and methotrexate (1). All therapies have potential toxicity, and psoriatic arthritis is often difficult to treat effectively (I). Recently, Smith et al (2) and others (3,4) reported the use of oral 1,25-dihydroxyvitamin D3 [l ,25(OH),D3] in patients with psoriasis; up to 70% of the patients achieved significant improvement in their skin lesions. Based on this experience, we began a therapeutic trial of oral 1 ,25(OH),D3 in patients with psoriatic arthritis to see if there was a beneficial effect on their arthritis, and, if