Adjuvant Sunitinib in High-Risk Patients with Uveal Melanoma: Comparison with Institutional Controls.

PURPOSE: To compare overall survival in high-risk patients with primary uveal melanoma who received adjuvant sunitinib with institutional controls. DESIGN: Retrospective cohort. PARTICIPANTS: Selection criteria were (1) monosomy 3 and 8q amplification by cytogenetic or DecisionDx-UM Class 2 and (2) monosomy 3 and large tumor size (T3-4 by American Joint Committee on Cancer classification). Exclusion criteria were date of diagnosis before 2007 or after 2013 and age <18 years. METHODS: A cohort of patients who intended to receive adjuvant sunitinib for 6 months was compared with institutional historical controls with the same risk factors. Kaplan-Meier and Cox proportional hazards models were used to analyze the outcome. Propensity score was used to adjust for nonrandom assignment to sunitinib. MAIN OUTCOME MEASURES: Overall survival. RESULTS: From the Wills Eye Hospital Oncology Service Uveal Melanoma Cytogenetic Database (N = 1172), 128 patients fulfilled the selection and exclusion criteria. Median follow-up was 52.7 months (range, 0.26-108 months). A total of 54 patients received sunitinib. Their median age was 56 years (range, 29-81 years), and 48% were men. A total of 74 historical controls in the same risk category were identified. Their median age was 62 years (21-80 years), and 48% were men. Patients in the sunitinib group had worse cytogenetic or molecular features (monosomy 3 and 8q amplification or class 2 87% vs. 57%; P < 0.001), had smaller tumor sizes (T3-4 56% vs. 83%; P = 0.001), and were younger. There were 51 deaths, 14 (26%) in the sunitinib group and 37 (50%) in the control group. In the univariate analysis, the sunitinib group had longer overall survival (hazard ratio, 0.53; 95% confidence interval, 0.29-0.99; P = 0.041). In multivariate Cox regression analysis, interaction between use of sunitinib and age as a dichotomous variable was highly significant (P = 0.003). The following variables were statistically associated with prediction of overall survival: cytogenetic/molecular status (P = 0.015), T-size category (P = 0.022), gender (P = 0.040), and adjuvant sunitinib in patients aged <60 years (P = 0.004). Results were confirmed by propensity score analysis. CONCLUSIONS: In this retrospective study, the use of sunitinib in the adjuvant setting was associated with better overall survival.

Impact of a patient-centered medical home clerkship curriculum.

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the impact of a patient-centered medical home (PCMH) curriculum introduced in a family medicine clerkship in 2011--2012. This new curriculum introduced third-year students to the PCMH using a variety of interactive educational formats, including case-based, online, and experiential PCMH activities. METHODS: Qualitative analysis of student reflection essays explored themes based on PCMH experiences during family medicine clerkships. RESULTS: Pre-curricular needs assessment revealed an important gap in students' exposure to and knowledge of PCMH concepts consistent with existing literature. Qualitative thematic analysis examined students' perceptions of patient experiences in PCMH practices but also revealed rich, unprompted, and very positive perceptions of student and provider roles and system-based changes in the PCMH model. Only 2.3% of coded references (n=10, out of 435) described "negative" emotional reactions to PCMH experiences. More than half of student essays described important changes in self-assessed knowledge, skills, and attitudes, another significant and unexpected result. CONCLUSIONS: Successful implementation of innovative PCMH curricula is key to preparing a workforce ready to practice in a new model of health care delivery. This qualitative study demonstrates that an experiential PCMH curriculum can enhance third-year medical student self-assessed knowledge of and attitudes toward the PCMH and may improve perceptions of a career in primary care.

24-hour profiles of circulating ghrelin and peptide YY are inversely associated in normal weight premenopausal women.

Peptide YY (PYY) and ghrelin (GHR) may modulate one another's actions within the hypothalamus. Peripheral infusion of PYY in humans acutely suppresses circulating concentrations of GHR. Whether an association between PYY and GHR exists in the peripheral circulation of humans over 24h is unknown. The purpose of this study was to determine if circulating concentrations of PYY and GHR were significantly associated over 24h in humans. Participants (n=13) were normal weight, moderately active, women ages 18-24 yr. Blood samples were obtained q10 min for 24 h and assayed using RIA for total PYY and total GHR hourly from 0800 to 1000 h and 2000 to 0800 h and q20 min from 1000 to 2000 h. Dietary intake during the 24 h procedure was comprised of 55% carbohydrates, 30% fat, and 15% protein (three meals and a snack). Statistical analyses included linear mixed-effects modeling to test whether PYY predicted GHR concentrations over 24h. Participants weighed 57.0±1.5 kg and had 26.1±1.5% body fat (15.0±1.1 kg), 42.1±1.1 kg fat free mass, a BMI of 21.3±0.5 kg/m(2) and RMR of 1072±28 kcal/24 h. Visually, PYY and GHR exhibited an inverse association over nearly the entire 24h period. Statistically, circulating concentrations of 24 h PYY predicted 24 h GHR (ghrelin=1860.51-2.14*PYY; p=0.04). Circulating concentrations of PYY are inversely associated with GHR over 24 h. These data provide evidence that PYY may contribute to the modulation of the secretion of GHR in normal weight, premenopausal women over a 24 h period and supports similar inferences from experimental studies in animals and humans.