Attrition of Patients on a Precision Oncology Trial: Analysis of the I-PREDICT Experience.

BACKGROUND: Precision oncology uses molecular profiling of tumors to identify biomarker-tailored therapies for patients in the hope of improving outcomes. Typically, only a minority of patients receives evaluable matched treatment. This study explored the reasons for attrition on a precision medicine trial. MATERIALS AND METHODS: Study participants were 190 adult patients who consented to the I-PREDICT (Investigation of molecular Profile-Related Evidence Determining Individualized Cancer Therapy) trial. Patients had metastatic and/or unresectable incurable malignancies. Patients who were not evaluable were analyzed. RESULTS: Of consented patients, 44% were not evaluable. Men were twice as likely to be not evaluable as women. Prominently, 45% of patients who were not evaluable dropped off because of death, hospice referral, or decline in organ function. CONCLUSION: Health deterioration of consented patients is a significant barrier to being evaluable on the I-PREDICT trial. These data suggest that patients are enrolled on precision oncology trials too late in their disease course or with excessive disease burden.

Psychosocial and neighborhood correlates of health-related quality of life: A multi-level study among Hispanic adults.

OBJECTIVE: Improvement in health-related quality of life (HRQoL) is a public health goal of Healthy People 2020. Hispanics living in the United States are at risk for poor HRQoL, but the causes and correlates of this risk are not well understood. Thus, the present study examined individual-level psychosocial and neighborhood-level built environment correlates of physical and mental HRQoL among Hispanic adults. METHOD: A community sample of Hispanic adults (N = 383) completed self-report health-related questionnaires, and census tract was used to collect data on neighborhood-level built environment variables. Multilevel modeling was used to examine individual-level psychosocial (language preference, religiosity, subjective social status, discrimination, and number of years lived in the United States) and neighborhood-level built-environment (the retail food environment, proximity to alcohol retailers, and tobacco retailer density) correlates of physical and mental HRQoL. RESULTS: Higher subjective social status was significantly associated with better HRQoL, and more experiences with discrimination were significantly associated with lower HRQoL. For physical HRQoL, these relationships were stronger in neighborhoods with a higher density of tobacco retail outlets. CONCLUSIONS: Findings from this study suggest that subjective social status and discrimination play important roles in HRQoL among Hispanics, in particular in neighborhoods with a higher density of tobacco retail outlets. This study highlights the importance of considering neighborhood context, and in particular neighborhood disadvantage, when examining the relationship between social status, discrimination and HRQoL among Hispanics. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Obesity, hyperphagia and increased metabolic efficiency in Pc1 mutant mice.

Prohormone convertase 1 (PC1) mutations lead to obesity in humans. However, Pc1 knockout mice do not become obese; in fact, they are runted due to a defect in growth-hormone releasing hormone processing, leading to the speculation that PC1 subserves different functions between mouse and human. Here, we report a novel allele of mouse Pc1 (N222D) that leads to obesity, abnormal proinsulin processing and multiple endocrinological defects. Increased energy intake and a more efficient metabolism contribute to the obesity in Pc1(N222D/N222D) mice. Defective proinsulin processing leads to glucose intolerance, but neither insulin resistance nor diabetes develop despite obesity. The obesity is associated with impaired autocatalytic activation of mature PC1 and reduced hypothalamic alpha-MSH. This is the first characterization of Pc1 mutation in a model organism that mimics human PC1 deficiency.