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.

Markers of mineral metabolism are not associated with aortic pulse wave velocity in community-living elderly persons: the Health Aging and Body Composition study.

BACKGROUND: Disorders in mineral metabolism are associated with risk for cardiovascular disease (CVD) events in patients with kidney disease as well as in the general population. This risk is thought to be mediated, in part, through the mechanism of stiffening of the arteries. METHODS: The objective of this study was to evaluate the relationships between serum calcium, phosphorus, intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D levels and arterial pulse wave velocity (aPWV) among 2,229 community-dwelling elderly persons participating in the Health Aging and Body Composition (Health ABC) study. RESULTS: The mean age of the participants was 72 years; 52% were woman, 39% were black, and 17% had chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)). In parallel unadjusted analyses, the following associations were observed: 2.86% greater aPWV per 12 ng/ml (s.d.) lower 25-hydroxyvitamin D (95% confidence interval -4.38%, -1.31%), 3.04% greater aPWV per 28 pg/ml (s.d.) higher iPTH (95% confidence interval 1.42-4.68%), and 2.37% lower aPWV per 0.5 mg/dl (s.d.) higher phosphorus (95% confidence interval -3.90% to - 0.81%). Except for phosphorus, these associations were attenuated and rendered no longer statistically significant after adjustment for demographic risk factors, clinical site, season, medications and other CVD risk factors. The results were similar in men and women and were not dependent on the presence of CKD. CONCLUSIONS: Among well-functioning community-dwelling elderly persons, only serum phosphorus was associated with aPWV; and this association was in the opposite direction of the one hypothesized. Factors other than vascular stiffening may mediate the relationship between disordered mineral metabolism and CVD events in community-living elders.

Associations of estradiol and testosterone with serum phosphorus in older men: the Osteoporotic Fractures in Men study.

Postmenopausal women consistently have higher phosphorus levels than similarly aged men. As it is known that estradiol induces phosphaturia in rodents, we evaluated the cross-sectional association of sex hormones with serum phosphorus in 1346 community-living older men (mean age 76) of which 18% had moderate (stage 3) kidney disease. Using linear regression with serum phosphorus levels as the dependent variable, we found that for each 10 pg/ml higher total estradiol level there was a statistically significant 0.05 mg/dl lower serum phosphorus when adjusted for age, ethnicity, testosterone, sex hormone-binding globulin, calcium, estimated glomerular filtration rate, intact parathyroid hormone, 25(OH) vitamin D, bone mineral density, and alkaline phosphatase. These results were similar in individuals with or without chronic kidney disease. Serum testosterone concentrations were also statistically significantly associated with lower serum phosphorus levels. We confirmed these results in an independent sample of 2555 older men, wherein these associations were not attenuated when adjusted for fibroblast growth factor-23 levels. Hence, our study of community-living older men suggests that estradiol may directly or indirectly induce phosphaturia in humans. The mechanism responsible for the association of testosterone with serum phosphorus remains to be determined.

Serum phosphorus levels and the spectrum of ankle-brachial index in older men: the Osteoporotic Fractures in Men (MrOS) study.

A higher serum phosphorus level is associated with cardiovascular disease (CVD) events among community-living populations. Mechanisms are unknown. The ankle-brachial index (ABI) provides information on both atherosclerosis and arterial stiffness. In this cross-sectional study (2000-2002), the authors evaluated the association of serum phosphorus levels with low (<0.90) and high (> or =1.40 or incompressible) ABI as compared with intermediate ABI in 5,330 older US men, among whom the mean serum phosphorus level was 3.2 mg/dL (standard deviation, 0.4), 6% had a low ABI, and 5% had a high ABI. Each 1-mg/dL increase in serum phosphorus level was associated with a 1.6-fold greater prevalence of low ABI (95% confidence interval (CI): 1.2, 2.1; P < 0.001) and a 1.4-fold greater prevalence of high ABI (95% CI: 1.0, 1.9; P = 0.03) in models adjusted for demographic factors, traditional CVD risk factors, and kidney function. However, the association of phosphorus with high ABI differed by chronic kidney disease (CKD) status (in persons with CKD, prevalence ratio = 2.96, 95% CI: 1.61, 5.45; in persons without CKD, prevalence ratio = 1.14, 95% CI: 0.81, 1.61; interaction P = 0.04). In conclusion, among community-living older men, higher phosphorus levels are associated with low ABI and are also associated with high ABI in persons with CKD. These associations may explain the link between serum phosphorus levels and CVD events.

Fetuin-A and BMD in older persons: the Health Aging and Body Composition (Health ABC) study.

Fetuin-A is a hepatic secretory protein that promotes bone mineralization in vitro. Whether fetuin-A levels are associated with BMD in humans is unknown. The Health Aging and Body Composition study enrolled 3075 well-functioning black and white persons 70-79 yr of age and measured BMD. This cross-sectional study measured serum fetuin-A using ELISA among a random sample of 508 participants within sex and race strata. Multivariate linear regression analysis evaluated the associations of fetuin-A with BMD. Among women (n = 257), higher fetuin-A levels were significantly associated with higher total hip (p = 0.02), lumbar spine (p = 0.03), and whole body BMD (p = 0.01) in models adjusted for age, race, diabetes, alcohol and tobacco use, physical activity, body mass index, C-reactive protein levels, calcium supplement, and estrogen use. For example, each SD (0.38 g/liter) higher level of fetuin-A was associated with 0.016 g/cm(2) higher total hip areal BMD. The association was of similar magnitude and direction for femoral neck BMD but did not reach statistical significance (p = 0.11). In contrast, among men (n = 251), fetuin-A had no significant associations with total hip (p = 0.79), lumbar spine (p = 0.35), whole body (p = 0.46), or femoral neck BMD (p = 0.54) in multivariable models. We conclude that higher fetuin-A levels are independently associated with higher BMD among well-functioning community-dwelling older women but not older men. Future studies should evaluate whether fetuin-A may refine fracture risk assessment in older women.