Clinical Outcomes, Costs, and Healthcare Resource Utilization in Patients with Metastatic Merkel Cell Carcinoma Treated with Immune Checkpoint Inhibitors vs Chemotherapy.

PURPOSE: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with poor prognosis. This study compared patient characteristics, comorbidities, adverse events (AEs), treatment persistence, healthcare resource utilization (HRU) and costs in patients with metastatic MCC (mMCC) treated with immune checkpoint inhibitors (ICIs) or recommended chemotherapy per 2018 National Comprehensive Cancer Network (NCCN) Guidelines. PATIENTS AND METHODS: A retrospective, observational study was conducted using data from 3/1/2015 through 12/31/2017 from the Premier Healthcare Database, a US hospital discharge database. The study included patients aged ≥12 years with International Classification of Diseases Codes for MCC and metastasis, categorized by their first treatment (index) during the study period (ICI or NCCN-recommended chemotherapy [chemotherapy]). Patient, hospital, and visit characteristics were assessed at the index date and Charlson Comorbidity Index (CCI) score and comorbidities during a 6-month look-back period. Clinical outcomes, including AEs and treatment persistence were assessed over 90 days and HRU and costs over 180 days post-index. RESULTS: Of 75 patients with mMCC receiving ICIs (n=37) or chemotherapy (n=38), mean age was ≈73 years, and 21.3% had a history of immune-related (IR) conditions. Overall, ICI- and chemotherapy-treated patients were similar in most baseline characteristics, IR comorbidities, and CCI score. However, more ICI patients (46%) than chemotherapy patients (26%) persisted on treatment over 90-day follow-up, odds ratio (95% CI): 2.04 (0.93, 4.47), P=0.07. Over 180-day follow-up, 33% of patients had an inpatient admission with mean length of stay (LOS) ≈2 days shorter for ICI vs chemotherapy (not statistically significant). Total costs, primarily driven by pharmacy costs, were higher for ICIs than chemotherapy; other departmental costs were similar between treatment groups. CONCLUSION: In a real-world setting, patients with mMCC receiving ICIs had higher treatment persistence over 90 days, shorter inpatient LOS and similar departmental cost (excluding pharmacy cost) than those receiving chemotherapy.

Dietary Long-Chain n-3 Fatty Acid Intake and Arthritis Risk in the Women's Health Initiative.

BACKGROUND: The prevalence of arthritis in the United States is substantial and on the rise. Long-chain n-3 polyunsaturated fatty acids, which have anti-inflammatory properties, have been shown to provide therapeutic benefit to arthritis patients; however, to date few have examined these associations with arthritis risk. OBJECTIVE: The study objective was to examine the associations of long-chain n-3 polyunsaturated fatty acids intake with osteoarthritis (OA) and rheumatoid arthritis (RA) risk among postmenopausal women. DESIGN: This was a prospective cohort study. PARTICIPANTS: The sample for this analysis consisted of 80,551 postmenopausal women, aged 55 to 79 years and with no history of arthritis, recruited into the Women's Health Initiative Observational Study and Clinical Trials cohort between 1993 and 1998. Women completed a 120-item food frequency questionnaire at baseline. MAIN OUTCOME MEASURES: After a median follow-up of 8 years, 22,306 incident OA and 3,348 RA cases were identified. STATISTICAL ANALYSES PERFORMED: Adjusted Cox regression models were used to estimate hazard ratios and 95% CI for the associations between dietary LCn-3PUFA intake and OA and RA risk. RESULTS: Individual and total long-chain n-3 polyunsaturated fatty acids (Quintile 5 vs Quintile 1: hazard ratio 1.04, 95% CI 0.99 to 1.09 for OA; hazard ratio 1.01, 95% CI 0.90 to 1.13 for RA) were not associated with OA and RA risk. Further, no associations were observed between n-6 polyunsaturated fatty acids intake and either arthritis outcome. CONCLUSIONS: This study is the first to examine associations of long-chain n-3 polyunsaturated fatty acids intake with OA risk and the largest to examine associations with RA risk. Despite their therapeutic potential, the study provides no evidence of benefit of these nutrients in relation to arthritis risk.

Severe obesity, heart disease, and death among white, African American, and Hispanic postmenopausal women.

OBJECTIVE: To compare mortality, nonfatal coronary heart disease (CHD), and congestive heart failure (CHF) risk across BMI categories in white, African American, and Hispanic women, with a focus on severe obesity (BMI ≥ 40), and examine heterogeneity in weight-related CHD risk. METHODS: Among 156,775 Women's Health Initiative observational study and clinical trial participants (September 1993-12 September 2005), multivariable Cox models estimated relative risk for mortality, CHD, and CHF. CHD incidence was calculated by anthropometry, race, and cardiovascular risk factors (CVRF). RESULTS: Mortality, nonfatal CHD, and CHF incidence generally rose with BMI category. For severe obesity versus normal BMI, hazard ratios (HRs, 95% confidence interval) for mortality were 1.97 (1.77-2.20) in white, 1.55 (1.20-2.00) in African American, and 2.59 (1.55-4.31) in Hispanic women; for CHD, HRs were 2.05 (1.80-2.35), 2.24 (1.57-3.19), and 2.95 (1.60-5.41) respectively; for CHF, HRs were 5.01 (4.33-5.80), 3.60 (2.30-5.62), and 6.05 (2.49-14.69). CVRF variation resulted in substantial variation in CHD rates across BMI categories, even in severe obesity. CHD incidence was similar by race/ethnicity when differences in BMI or CVRF were accounted for. CONCLUSIONS: Severe obesity increases mortality, nonfatal CHD, and CHF risk in women of diverse race/ethnicity. CVRF heterogeneity contributes to variation in CHD incidence even in severe obesity.

Pulse wave velocity is associated with ß-amyloid deposition in the brains of very elderly adults.

OBJECTIVE: To determine arterial stiffness and ß-amyloid (Aß) deposition in the brain of dementia-free older adults. METHODS: We studied a cohort of 91 dementia-free participants aged 83-96 years. In 2009, participants completed brain MRI and PET imaging using Pittsburgh compound B (PiB; a marker of amyloid plaques in human brain). In 2011, we measured resting blood pressure (BP), mean arterial pressure (MAP), and arterial stiffness by pulse wave velocity (PWV) in the central, peripheral, and mixed (e.g., brachial ankle PWV [baPWV]) vascular beds, using a noninvasive and automated waveform analyzer. RESULTS: A total of 44/91 subjects were Aß-positive on PET scan. Aß deposition was associated with mixed PWV, systolic BP, and MAP. One SD increase in baPWV resulted in a 2-fold increase in the odds of being Aß-positive (p = 0.007). High white matter hyperintensity (WMH) burden was associated with increased central PWV, systolic BP, and MAP. Compared to Aß-negative individuals with low WMH burden, each SD increase in PWV was associated with a 2-fold to 4-fold increase in the odds of being Aß-positive and having high WMH. CONCLUSIONS: Arterial stiffness was associated with Aß plaque deposition in the brain, independent of BP and APOE ε4 allele. The associations differed by type of brain abnormality and vascular bed measured (e.g., WMH with central stiffness and Aß deposition and mixed stiffness). Arterial stiffness was highest in individuals with both high Aß deposition and WMH, which has been suggested to be a "double hit" contributing to the development of symptomatic dementia.