Effectiveness and Safety of Apixaban Versus Warfarin in Obese Patients with Nonvalvular Atrial Fibrillation Enrolled in Medicare and Veteran Affairs.

Real-world studies have evaluated the use of anticoagulants in obese patients with nonvalvular atrial fibrillation (NVAF), but they have been limited by sample size or the use of diagnosis codes on claims to define obesity. This retrospective study used body weight data of ≥100 kg or a body mass index of ≥30 kg/m2 to identify elderly (aged ≥65 years) NVAF patients with obesity in dually enrolled Veterans Affairs and fee-for-service Medicare patients. It evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) in patients that initiated apixaban versus warfarin. Stabilized inverse probability treatment weighting was used to balance the baseline characteristics between patients prescribed apixaban and warfarin in obese patients. Cox models were used to evaluate the relative risk of stroke/SE and MB. Overall, 35.9% (n = 26,522) of the NVAF population were obese, of which 13,604 apixaban and 12,918 warfarin patients were included. After inverse probability treatment weighting, patient characteristics were balanced. The mean age was 75 years, the mean CHA2DS2-VASc score (Congestive Heart Failure, Hypertension, Age ≥75 [Doubled], Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack [Doubled], Vascular Disease, Age 65-74, Female) was 3.8, the mean HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) Score was ∼2.6, and >98% of patients were males. Obese apixaban patients were associated with a similar risk of stroke/SE (hazard ratio: 0.82; 95% confidence interval: 0.66 to 1.03) and a significantly lower risk of MB (hazard ratio: 0.62; 95% confidence interval: 0.54 to 0.70) versus warfarin. No significant interaction was observed between treatment and obesity status (nonobese, obese/nonmorbid, obese/morbid) for stroke/SE (interaction p = 0.602) or MB (interaction p = 0.385). In obese patients with NVAF, apixaban was associated with a similar risk of stroke/SE and a significantly lower risk of MB versus warfarin.

Treatment patterns and survival in metastatic castration-sensitive prostate cancer in the US Veterans Health Administration.

BACKGROUND: Limited real-world data exist on treatment patterns and outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: A retrospective cohort study was conducted, using the Veterans Health Administration claims database (April 2013-March 2018). Among 369,734 prostate cancer patients, we selected all men who developed metastases within 90 days before or after medical/surgical castration and who received androgen deprivation therapy (ADT). Patients were categorized into four cohorts: ADT-only (± <90-day nonsteroidal anti-androgen [NSAA] use), ADT + NSAA, ADT + docetaxel, and ADT + abiraterone. Main outcomes were treatment patterns, time-to-progression to metastatic castration-resistant disease, and overall survival. Multivariable analysis and sensitivity analysis were conducted. RESULTS: Of 1395 patients, 874 (63%) received ADT-only, 338 (24%) received ADT + NSAA, 108 (8%) received ADT + docetaxel, and 75 (5%) received ADT + abiraterone. Proportions on ADT-only and ADT + NSAA declined (from 66% to 60% and from 31% to 17%, respectively) over the study period, while proportions prescribed ADT + docetaxel or abiraterone increased from 3% to 9% and from 1% to 15%, respectively. Patients treated with ADT + NSAA had similar risks of castration-resistant disease (hazard ratio [HR] 1.05; 95% confidence interval [CI]: 0.87, 1.26) and overall mortality (HR 1.22; 95% CI: 0.97, 1.54) as ADT-only. CONCLUSIONS: Most patients with mCSPC initiating ADT received ADT-only or ADT + NSAA, despite the emergence of docetaxel and novel hormonal therapies. Even in the most recent period (2017 to early 2018), only 24% of men received intensified therapy with agents known to prolong survival versus ADT-only. These data in real-world clinical practice suggest substantial room for improved outcomes in patients with mCSPC.

Early Plasma Matrix Metalloproteinase Profiles. A Novel Pathway in Pediatric Acute Respiratory Distress Syndrome.

RATIONALE: MMPs (Matrix metalloproteinases) and their endogenous tissue inhibitors may contribute to lung injury through extracellular matrix degradation and modulation of inflammation and fibrosis. OBJECTIVES: To test for an association between MMP pathway proteins and inflammation, endothelial dysfunction, and clinical outcomes. METHODS: We measured MMPs in plasma collected on acute respiratory distress syndrome (ARDS) Day 1 from 235 children at five hospitals between 2008 and 2017. We used latent class analysis to identify patients with distinct MMP profiles and then associated those profiles with markers of inflammation (IL-1RA, -6, -8, -10, and -18; macrophage inflammatory protein-1α and -1ß; tumor necrosis factor-α and -R2), endothelial injury (angiopoietin-2, von Willebrand factor, soluble thrombomodulin), impaired oxygenation (PaO2/FiO2 [P/F] ratio, oxygenation index), morbidity, and mortality. MEASUREMENTS AND MAIN RESULTS: In geographically distinct derivation and validation cohorts, approximately one-third of patients demonstrated an MMP profile characterized by elevated MMP-1, -2, -3, -7, and -8 and tissue inhibitor of metalloproteinase-1 and -2; and depressed active and total MMP-9. This MMP profile was associated with multiple markers of inflammation, endothelial injury, and impaired oxygenation on Day 1 of ARDS, and conferred fourfold increased odds of mortality or severe morbidity independent of the P/F ratio and other confounders (95% confidence interval, 2.1-7.6; P < 0.001). Logistic regression using both the P/F ratio and MMP profiles was superior to the P/F ratio alone in prognosticating mortality or severe morbidity (area under the receiver operating characteristic curve, 0.75; 95% confidence interval, 0.68-0.82 vs. area under the receiver operating characteristic curve, 0.66; 95% confidence interval, 0.58-0.73; P = 0.009). CONCLUSIONS: Pediatric patients with ARDS have specific plasma MMP profiles associated with inflammation, endothelial injury, morbidity, and mortality. MMPs may play a role in the pathobiology of children with ARDS.