N THE PREANTIBIOTIC ERA, NATIVE valve endocarditis was virtually always fatal. Since the advent of antibiotic therapy, mortality decreased to 24% to 60% in published case series, with heart failure representing the leading cause of death. [1][2][3][4] During the past 3 decades, studies have suggested that valve surgery should be considered for patients with native valve endocarditis associated with complications that adversely affect prognosis: heart failure, 5-10 new valvular regurgitation, [11][12][13] refractory infection (ie, persistent fever or bacteremia, fungemia, or paravalvular abscess), 14,15 systemic embolization to vital organs, 16,17 and the presence of a vegetation on echocardiography as this represents a plausible risk for embolization. [18][19][20] However, methodological limitations of existing studies, the absence of randomized controlled trials, and the lack of a validated method to classify prognostic severity make management decisions problematic.Accurate prognostic classification may help facilitate individual treatment decisions and interpretation of therapeutic interventions in clinical trials. In this study, we derived and externally validated a prognostic classification system in 2 contemporaneous cohorts of adults with complicated leftsided native valve endocarditis. METHODS PatientsResearch patients were identified through systematic medical record review at the 7 Connecticut hospitals where valve surgery was performed. To create and test a prognostic classification system, we divided patients into derivation and validation cohorts (FIGURE). The derivation cohort (n = 259) was assembled from adults (Ͼ16 years) in whom complicated leftsided native valve endocarditis was di-

Context Complicated, left-sided native valve endocarditis causes significant morbidity and mortality in adults. The presumed benefits of valve surgery remain unproven due to lack of randomized controlled trials.Objective To determine whether valve surgery is associated with reduced mortality in adults with complicated, left-sided native valve endocarditis. Design and SettingRetrospective, observational cohort study conducted from January 1990 to January 2000 at 7 Connecticut hospitals. Propensity analyses were used to control for bias in treatment assignment and prognostic imbalances.Patients Of the 513 adults with complicated, left-sided native valve endocarditis, 230 (45%) underwent valve surgery and 283 (55%) received medical therapy alone.Main Outcome Measure All-cause mortality at 6 months after baseline. ResultsIn the 6-month period after baseline, 131 patients (26%) died. In unadjusted analyses, valve surgery was associated with reduced mortality (16% vs 33%; hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.29-0.63; PϽ.001). After adjustment for baseline variables associated with mortality (including hospital site, comorbidity, congestive heart failure, microbial etiology, immunocompromised state, abnormal mental status, and refractory infection), valve surgery remained associated with reduced mortality (adjusted HR, 0.35; 95% CI, 0.23-0.54; PϽ.02). In further analyses of 218 patients matched by propensity scores, valve surgery remained associated with reduced mortality (15% vs 28%; HR, 0.45; 95% CI, 0.23-0.86; P=.01). After additional adjustment for variables that contribute to heterogeneity and confounding within the propensity-matched group, surgical therapy remained significantly associated with a lower mortality (HR, 0.40; 95% CI, 0.18-0.91; P=.03). In this propensity-matched group, patients with moderate to severe congestive heart failure showed the greatest reduction in mortality with valve surgery (14% vs 51%; HR, 0.22; 95% CI, 0.09-0.53; P=.001). ConclusionsValve surgery for patients with complicated, left-sided native valve endocarditis was independently associated with reduced 6-month mortality after adjustment for both baseline variables associated with the propensity to undergo valve surgery and baseline variables associated with mortality. The reduced mortality was particularly evident among patients with moderate to severe congestive heart failure.

Background COVID-19 can lead to multiorgan failure. Dapagliflozin, a SGLT2 inhibitor, has significant protective benefits for the heart and kidney. We aimed to see whether this agent might provide organ protection in patients with COVID-19 by affecting processes dysregulated during acute illness.Methods DARE-19 was a randomised, double-blind, placebo-controlled trial of patients hospitalised with COVID-19 and with at least one cardiometabolic risk factor (ie, hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease). Patients critically ill at screening were excluded. Patients were randomly assigned 1:1 to dapagliflozin (10 mg daily orally) or matched placebo for 30 days. Dual primary outcomes were assessed in the intention-to-treat population: the outcome of prevention (time to new or worsened organ dysfunction or death), and the hierarchial composite outcome of recovery (change in clinical status by day 30). Safety outcomes, in patients who received at least one study medication dose, included serious adverse events, adverse events leading to discontinuation, and adverse events of interest. This study is registered with ClinicalTrials.gov, NCT04350593.

From 1982 to 1984, the authors conducted a population-based case-control study of lung cancer in men and women nonsmokers in New York State. In-person interviews were completed for 437 lung cancer cases (197 never smokers, 240 former smokers) and 437 matched population controls. Cases and controls were asked to report any history of physician-diagnosed nonmalignant lung disease; cases were more likely than controls to report such a history. Statistically significant associations were found for emphysema (odds ratio (OR) = 1.94, 95% confidence interval (CI) 1.10-3.43), chronic bronchitis (OR = 1.73, 95% CI 1.10-2.72), and the combined endpoint of emphysema, chronic bronchitis, or asthma (OR = 1.82, 95% CI 1.26-2.63). After adjustment for active and passive tobacco smoke exposure, emphysema, chronic bronchitis, and asthma (each condition and the combined endpoint) were significantly associated with lung cancer risk. The risk was more marked for squamous cell carcinomas and for subjects who were diagnosed at older ages, and it remained significant when surrogate interviews were excluded. These results are consistent with the hypothesis that certain prior lung conditions increase the risk of lung cancer in men and women nonsmokers.

The win ratio is a general method of comparing locations of distributions of two independent, ordinal random variables, and it can be estimated without distributional assumptions. In this paper we provide a unified theory of win ratio estimation in the presence of stratification and adjustment by a numeric variable. Building step by step on the estimate of the crude win ratio we compare corresponding tests with well known non-parametric tests of group difference (Wilcoxon rank-sum test, Fligner–Policello test, van Elteren test, test based on the regression on ranks, and the rank analysis of covariance test). We show that the win ratio gives an interpretable treatment effect measure with corresponding test to detect treatment effect difference under minimal assumptions.