Predicting No-shows at a Student-Run Comprehensive Primary Care Clinic.

BACKGROUND AND OBJECTIVES: Missed appointments represent a significant challenge to the efficient and effective provision of care in the outpatient setting. High no-show rates result in ineffective use of human resources and contribute to loss of follow-up. Shade Tree Clinic (STC) is a student-run, comprehensive primary care clinic that serves more than 350 Middle Tennessee residents. This study aimed to use available data to predict no-shows to improve clinic efficiency and service quality. METHODS: Data were pulled from clinic scheduling software for all appointments at STC between January 1, 2010 and December 31, 2015. Weather data were added for each appointment date using an online database. Multivariable logistic regression was used to create models from these historical data. RESULTS: A total of 13,499 appointments were included with an overall show rate of 69.2%. The final model contained previous show rate (OR 1.063; P<.001), day of the week (OR 1.20; P<.001), automated reminder (OR 1.40; P<.001), snow in inches (OR .33; P<.001), and high ambient temperature in degrees (OR 1.01; P<.001). Using a cutoff probability of the 25th percentile, the model had a negative predictive value of 61.0%. CONCLUSIONS: Based on readily available data and a novel conceptual framework, we can identify the quarter of patients least likely to present for scheduled appointments and target them for interventions, allowing care providers to more effectively address community health care disparities through the clinic. This analysis is replicable at any clinic using an electronic medical record.

MDM2 antagonists overcome intrinsic resistance to CDK4/6 inhibition by inducing p21.

Intrinsic resistance of unknown mechanism impedes the clinical utility of inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) in malignancies other than breast cancer. Here, we used melanoma patient-derived xenografts (PDXs) to study the mechanisms for CDK4/6i resistance in preclinical settings. We observed that melanoma PDXs resistant to CDK4/6i frequently displayed activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, and inhibition of this pathway improved CDK4/6i response in a p21-dependent manner. We showed that a target of p21, CDK2, was necessary for proliferation in CDK4/6i-treated cells. Upon treatment with CDK4/6i, melanoma cells up-regulated cyclin D1, which sequestered p21 and another CDK inhibitor, p27, leaving a shortage of p21 and p27 available to bind and inhibit CDK2. Therefore, we tested whether induction of p21 in resistant melanoma cells would render them responsive to CDK4/6i. Because p21 is transcriptionally driven by p53, we coadministered CDK4/6i with a murine double minute (MDM2) antagonist to stabilize p53, allowing p21 accumulation. This resulted in improved antitumor activity in PDXs and in murine melanoma. Furthermore, coadministration of CDK4/6 and MDM2 antagonists with standard of care therapy caused tumor regression. Notably, the molecular features associated with response to CDK4/6 and MDM2 inhibitors in PDXs were recapitulated by an ex vivo organotypic slice culture assay, which could potentially be adopted in the clinic for patient stratification. Our findings provide a rationale for cotargeting CDK4/6 and MDM2 in melanoma.

Competency Based Approach to Community Health (COACH): The methods of a family-centered, community-based, individually adaptive obesity randomized trial for pre-school child-parent pairs.

Competency-Based Approaches to Community Health (COACH) is a randomized controlled trial of a family-centered, community-based, and individually-tailored behavioral intervention for childhood obesity among Latino pre-school children. COACH focuses on improving personal agency for health behavior change by tailoring content to overcome contextual barriers. The intervention focuses on diet, physical activity, sleep, media use, and engaged parenting. The content is individually adapted based on routine assessments of competency in specific health behaviors using a mobile health platform and novel measurement tools developed by our team. In response to these regular assessments, health coaches provide tailored health behavior change strategies to help families focus on the areas where they decide to improve the most. The intervention consists of a 15-week group-based intensive phase, with weekly sessions delivered by health coaches in community centers. Following weekly sessions, a 3-month maintenance phase of the intervention consists of twice monthly coaching calls for participants to focus on individual health goals for their families. The primary outcome of the trial is child body mass index trajectory over 1 year. Secondary outcomes include parent body mass index change, child waist circumference, child diet, child physical activity, and other psychosocial mediators of child health behavior change. The control arm consists of a school readiness intervention, delivered by the Nashville Public Library. By applying a personalized approach to child behavior change, in the setting of both family and community, COACH aims to develop sustainable solutions for childhood obesity by supporting healthy childhood growth in low-income, minority preschool children.