Evaluation of a Pharmacist-Managed Diabetes Transitions of Care Medication Management Clinic.

PURPOSE: The purpose of this study was to determine the impact of a pharmacist-managed transitions of care (TOC) clinic on outcomes in a posthospitalization population with diabetes. METHODS: A retrospective single center cohort study utilized electronic health records to identify discharged patients followed by the inpatient endocrinology team. The primary outcome was 30-day readmission rates in the target population. Secondary outcomes include 90-day readmission rates, time to first follow-up, emergency department/urgent care encounters, change in A1C, retention with endocrinology, referrals for diabetes education, and types of interventions. The control group included patients prior to the initiation of the TOC clinic compared to patients seen in the TOC clinic, evenly matched by A1C. Readmission rates and other clinical data were queried up to 4 months after discharge. RESULTS: Patients in the TOC cohort had similar 30-day readmission rates compared to the non-TOC cohort and were found to have lower A1C values within 120 days of discharge. Overall, patients in the TOC cohort were more likely to have a follow-up appointment and had closer follow-up after discharge. CONCLUSION: This study highlights that although there was no difference in readmission rates, a pharmacist-managed diabetes TOC clinic may decrease time to follow-up and improve long-term diabetes outcomes.

Runner's Health Choices Questionnaire: Male College Cross-Country Runners' Perspectives on Health and Eating.

CONTEXT: Competitive cross-country runners train at much higher loads and with greater demands than recreational runners, posing a unique set of physiological and psychological challenges. Thus, identification of factors influencing health and nutritional choices in male cross-country runners is needed to help combat energy-related health issues. PURPOSE: To assess male college cross-country runners' perspectives regarding sport-related health and the factors impacting their eating behaviors. DESIGN: Cross-sectional survey. PARTICIPANTS/METHODS: The Runner's Health Choices Questionnaire was distributed to male college cross-country runners. Responses were analyzed using quantitative descriptive statistics. RESULTS: One hundred nineteen runners completed the survey. Runners reported a diverse range of factors impacting eating and health behaviors from athletic performance enhancement to enjoyment of food. Less than 6% of athletes ranked athletic trainer, registered dietitian, or physician as often consulted for nutrition/health information. However, 75% of runners said they would be somewhat likely or very likely to make dietary or health changes if given new or additional information by a health care provider. CONCLUSION: Male cross-country runners appear to try to balance a global desire to be healthy with individual preferences. Athletes may be receptive to nutritional education that utilizes a biopsychosocial model with mental and psychological health support, and intentional effort is needed to support runners' overall health.

Modulation of adipocyte size and fat pad weight via resveratrol releasing scaffolds implanted into the epididymal adipose tissue.

Lipid overload of the adipose tissue, which can be caused by overnutrition, underlies metabolic disease. We hypothesized that increasing the energy demand of adipose tissue is a promising strategy to combat excessive lipid accumulation. Resveratrol, a natural polyphenol, activates lipid catabolism in fat tissue; however, its clinical success is hindered by poor bioavailability. Here, we implanted resveratrol releasing poly(lactide-co-glycolide) scaffolds into epididymal fat to overcome its poor bioavailability with the goal of enhancing local lipid catabolism. In lean mice, resveratrol scaffolds decreased adipocyte size relative to scaffolds with no drug, a response that correlated with AMP kinase activation. Immunohistochemistry indicated that macrophages and multinucleated giant cells within the scaffold expressed carnitine palmitoyltransferase 1 (CPT1) at higher levels than other cells in the adipose tissue. Furthermore, resveratrol increased CPT1 levels in cultured macrophages. Taken together, we propose that resveratrol scaffolds decrease adipocyte size because resveratrol increases lipid utilization in scaffold-infiltrating immune cells, possibly through elevating CPT1 levels or activity. In a follow-up study, mice that received resveratrol scaffolds 28-day prior to a high-fat diet exhibited decreased weight gain, adipose tissue expansion, and adipocyte hypertrophy compared to mice with control scaffolds. Notably, this scaffold-based strategy required a single resveratrol administration compared to the daily regiment generally needed for oral administration. These results indicate that localized delivery of metabolism modulating agents to the adipose tissue may overcome issues with bioavailability and that the role of biomaterials should be further investigated in this therapeutic strategy for metabolic disease.

Scaffold Implant Into the Epididymal Adipose Tissue Protects Mice From High Fat Diet Induced Ectopic Lipid Accumulation and Hyperinsulinemia.

Ectopic lipid accumulation, the deposition of lipids in lean tissue, is linked to type 2 diabetes through an association with insulin resistance. It occurs when adipose tissue fails to meet lipid storage needs and there is lipid spillover into tissues not equipped to store them. Ectopic lipid contributes to organ dysfunction because lipids can interfere with insulin signaling and other signaling pathways. Clinical studies indicate that decreasing ectopic lipids through diet and exercise is effective in treating type 2 diabetes; however, its prevalence continues to rise. We propose that strategies to improve lipid handling in the adipose tissue would be adjunctive to healthy lifestyle modification and may address difficulties in treating type 2 diabetes and other syndromes spurred by ectopic lipid. Herein, we investigate biomaterial implants as a means to increase lipid utilization in adipose tissue through the recruitment of highly metabolic cells. Poly(lactide-co-glycolide) scaffolds were implanted into the epididymal fat of mice fed a high fat diet that overwhelms the adipose tissue and promotes ectopic lipid accumulation. Over 5 weeks, mice with scaffolds gained less weight compared to mice without scaffolds and were protected from hyperinsulinemia. These effects correlated with a 53% decrease in triglyceride in the gastrocnemius and a 25% decrease in the liver. Scaffolds increased CPT1A protein levels in the epididymal fat and histology revealed high expression of CTP1A in the cells infiltrating the scaffold relative to the rest of the fat pad. In addition, lacing the scaffold with resveratrol increased CPT1A expression in the epididymal fat over scaffolds with no drug; however, this did not result in further decreases in weight gain or ectopic lipid. Mechanistically, we propose that the cellular activity caused by scaffold implant mitigates the lipid load imposed by the high fat diet and leads to a substantial decrease in lipid accumulation in the muscle and liver. In conclusion, this study establishes that a tissue engineering approach to modulate lipid utilization in the epididymal fat tissue can mitigate ectopic lipid accumulation in mice fed a high fat diet with positive effects on weight gain and whole-body insulin resistance.

A phase I trial of the γ-secretase inhibitor MK-0752 in combination with gemcitabine in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: The Notch pathway is frequently activated in cancer. Pathway inhibition by γ-secretase inhibitors has been shown to be effective in pre-clinical models of pancreatic cancer, in combination with gemcitabine. METHODS: A multi-centre, non-randomised Bayesian adaptive design study of MK-0752, administered per os weekly, in combination with gemcitabine administered intravenously on days 1, 8 and 15 (28 day cycle) at 800 or 1000 mg m-2, was performed to determine the safety of combination treatment and the recommended phase 2 dose (RP2D). Secondary and tertiary objectives included tumour response, plasma and tumour MK-0752 concentration, and inhibition of the Notch pathway in hair follicles and tumour. RESULTS: Overall, 44 eligible patients (performance status 0 or 1 with adequate organ function) received gemcitabine and MK-0752 as first or second line treatment for pancreatic cancer. RP2Ds of MK-0752 and gemcitabine as single agents could be combined safely. The Bayesian algorithm allowed further dose escalation, but pharmacokinetic analysis showed no increase in MK-0752 AUC (area under the curve) beyond 1800 mg once weekly. Tumour response evaluation was available in 19 patients; 13 achieved stable disease and 1 patient achieved a confirmed partial response. CONCLUSIONS: Gemcitabine and a γ-secretase inhibitor (MK-0752) can be combined at their full, single-agent RP2Ds.