Background
Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known.
Methods
We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15.
Results
A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P=0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, −5.0 percentage points; 95% CI, −9.8 to −0.3; P=0.03), as were new infections (5.9% vs. 11.2%; difference, −5.3 percentage points; 95% CI, −8.7 to −1.9; P=0.003).
Conclusions
Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number,
NCT04401579
.)
Data for 479 patients were analyzed to assess the impact of methicillin resistance on the outcomes of patients with Staphylococcus aureus surgical site infections (SSIs). Patients infected with methicillin-resistant S. aureus (MRSA) had a greater 90-day mortality rate than did patients infected with methicillin-susceptible S. aureus (MSSA; adjusted odds ratio, 3.4; 95% confidence interval, 1.
5-7.2). Patients infected with MRSA had a greater duration of hospitalization after infection (median additional days, 5;), although this was not significant P ! .001 on multivariate analysis ( ). Median hospital charges were $29,455 for control subjects, $52,791 for P p .11 patients with MSSA SSI, and $92,363 for patients with MRSA SSI ( for all group comparisons). Patients P ! .001 with MRSA SSI had a 1.19-fold increase in hospital charges ( ) and had mean attributable excess charges P p .03 of $13,901 per SSI compared with patients who had MSSA SSIs. Methicillin resistance is independently associated with increased mortality and hospital charges among patients with S. aureus SSI.Although methicillin-resistant Staphylococcus aureus (MRSA) is an increasingly common pathogen, the independent contribution of methicillin resistance to the outcomes for patients with S. aureus infection is unclear because patients who develop MRSA infections are typically older and sicker than are patients who develop methicillin-susceptible S. aureus (MSSA) infection. Surgical site infection (SSI) complicates 2%-5% of all
In this large, prospective, multinational cohort, more than one half of all cases of non-HACEK gram-negative bacillus endocarditis were associated with health care contact. Non-HACEK gram-negative bacillus endocarditis is not primarily a disease of injection drug users.
Hemodialysis-dependent patients with MSSA bacteremia treated with vancomycin are at a higher risk of experiencing treatment failure than are those receiving cefazolin. In the absence of patient specific circumstances (e.g., allergy to beta-lactams), vancomycin should not be continued beyond empirical therapy for hemodialysis-dependent patients with MSSA bacteremia.
Community-dwelling, hemodialysis-dependent patients hospitalized with MRSA bacteremia face a higher mortality risk, longer hospital stays, and higher inpatient costs than do patients with MSSA bacteremia.
Differences between clinical characteristics of patients with infective endocarditis who receive medical therapy versus patients who receive surgical and medical therapy are paramount. After controlling for inherent treatment selection bias and imbalances in prognostic factors using propensity score methodology, risk factors associated with increased long-term mortality included diabetes mellitus, the presence of a chronic catheter at the onset of infection, and paravalvular complications. In contrast, surgical therapy was associated with a significant long-term survival benefit.
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