ß-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain.

Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). Here, we identify ß-hydroxybutyrate (ßHB), a ketone body, as a regulator of protein solubility in the aging brain. ßHB is a small molecule metabolite which primarily provides an oxidative substrate for ATP during hypoglycemic conditions, and also regulates other cellular processes through covalent and noncovalent protein interactions. We demonstrate ßHB-induced protein insolubility across in vitro, ex vivo, and in vivo mouse systems. This activity is shared by select structurally similar metabolites, is not dependent on covalent protein modification, pH, or solute load, and is observable in mouse brain in vivo after delivery of a ketone ester. Furthermore, this phenotype is selective for pathological proteins such as amyloid-ß, and exogenous ßHB ameliorates pathology in nematode models of amyloid-ß aggregation toxicity. We have generated a comprehensive atlas of the ßHB-induced protein insolublome ex vivo and in vivo using mass spectrometry proteomics, and have identified common protein domains within ßHB target sequences. Finally, we show enrichment of neurodegeneration-related proteins among ßHB targets and the clearance of these targets from mouse brain, likely via ßHB-induced autophagy. Overall, these data indicate a new metabolically regulated mechanism of proteostasis relevant to aging and AD.

Asthma-chronic obstructive pulmonary disease overlap and cost-related medication non-adherence among older adults in the United States.

BACKGROUND: Cost-related medication non-adherence (CRN) can negatively impact health outcomes in older adults with asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO) by reducing access and adherence to essential medications. The objective of this study is to examine the association of ACO to any CRN and specific forms of CRN among a nationally representative sample of older (age ≥ 65 years) adults. METHODS: We adopted a cross-sectional study design using data from pooled cross-sectional Medicare Current Beneficiary Surveys (MCBS) (2006-2013) and linked fee-for-service Medicare claims. Unadjusted and adjusted logistic regressions that accounted for the complex survey design examined the association of ACO to any CRN and specific forms of CRN. RESULTS: Among older adults with ACO, 16% reported any CRN. The most common form of CRN was "failing to get prescription". As compared to older adults with no asthma and no COPD, those with ACO were more likely to report any CRN (adjusted odds ratios [AOR] = 1.50, 95%CI = [1.14, 1.96]) and all forms of CRN. However, when the number of unique medications was added to the model, there were no statistically significant differences in CRN between the two groups. CONCLUSIONS: Older adults with ACO represent a vulnerable population with increased risk for CRN. Multiple factors can contribute to CRN including: a higher number of prescribed medications, multiple co-morbidities, and cost of therapies. Medication comprehensive review interventions have the potential of reducing the risk of CRN among the older Medicare beneficiaries with ACO.

Obesity and health-related quality of life: a cross-sectional analysis of the US population.

OBJECTIVE: To examine the relationship between body mass index (BMI) and health-related quality-of-life (HRQL), in the presence of dietary controls and/or exercise in a national sample in the United States. METHODS: BMI and its association with HRQL domains (physical, mental and activity limitations) were examined using the Centers' for Disease Control and Prevention's 2000 Behavioral Risk Factor Surveillence System (BRFSS) data, after adjusting for various sociodemographic factors, self-reported health-status, and diet/exercise behavior. RESULTS: Based on World Health Organization's (WHO) classification of obesity, the study sample (N=182 372) included approximately 43.7% nonoverweight, 36% overweight, 14% obese, and 7% severely obese respondents. Exercise and dietary modifications were used by 17.5% of overweight, 15.2% of obese, and 12.5% of severely obese individuals. Logistic regression results using nonoverweight BMI as the reference category showed that severely obese (OR=1.87, 95% CI 1.64-2.12) and obese (OR=1.21, 95% CI 1.09-1.33) were more likely to experience greater than 14 unhealthy days affecting the physical health domain. Severely obese (OR=1.41, 95% CI 1.26-1.59) and obese (OR=1.17, 95% CI 1.07-1.28) were also more likely to experience greater than 14 unhealthy days affecting the mental health domain. Similarly, severely obese (OR=1.73, 95% CI 1.50-1.99) and obese (OR=1.22, 95% CI 1.08-1.37) were more likely to experience greater than 14 days with activity limitations. Exercise and dietary controls were associated with better HRQL across all three domains. CONCLUSION: The study highlights the relationship between BMI and HRQL in the United States. The study also underlines the positive correlation of exercise and dietary modifications with HRQL.

Pharmacists' preferences for continuing education and certificate programs.

OBJECTIVE: To conduct an assessment of the needs and interests of West Virginia pharmacists with respect to continuing education (CE) and certificate programs (CP) versus a nontraditional PharmD program (NTP). METHODS: A cross-sectional study was conducted. The survey was mailed to 2800 West Virginia University School of Pharmacy alumni and West Virginia licensed pharmacists. The survey collected data pertaining to pharmacists' perceptions for the needs of CE, CP, and the NTP program; the optimal structuring of these programs; and the demographics of participants. RESULTS: A 24% (674) usable response rate was achieved from two mailings. Respondents were asked to address all areas of interest: approximately 75% showed interest in enrolling in CE, 45% in CP, and 40% in the NTP program. Interest levels varied across demographic and practice characteristics. Seven methods of instruction were evaluated by pharmacists, with live lectures being the most preferred for both CE and CP. Interest for specific content areas and topics for CE workshops and CP were identified. The type and amount of employer support and willingness to pay for enrollment in the two types of programs were obtained. Markets' needs for CE and CP were identified for five typical pharmacists' profiles (e.g., staff pharmacists in community practice). CONCLUSIONS: Results can be used by CE providers to develop CE and CP programs of most interest to pharmacists and target them to appropriate demographic segments in order to be cost-effective.

Pharmacy immunization partnerships: a rural model.

OBJECTIVES: To describe the Pharmacy Immunization Project, a pharmacy/county health department (CHD) partnership model for immunizing infants and adults in rural areas, and to develop service procedures and disseminate lessons learned for adapting the model to different settings. SETTING: Independent community pharmacies in five contiguous rural counties in West Virginia. PRACTICE DESCRIPTION: Participating pharmacies varied markedly in space, prescription volume, and population of service areas. PRACTICE INNOVATION: Childhood and adult immunization service. INTERVENTIONS: Pharmacists partnered with nurses from CHDs to offer year-round immunizations at times when other providers were typically closed. Working under standing orders of the CHD medical directors, nurses also conducted routine well-baby examinations in the pharmacy. Promotions involved direct mailing, posters, fliers, direct communication, and ads in newspapers, radio, and TV. MAIN OUTCOME MEASURES: Pharmacists' and CHDs' continued willingness to participate, use of the service by local citizens, and feedback from participants and other health care providers and the West Virginia Immunization Program (WVIP). RESULTS: All sites except one continued their participation through the life of the project. The one exception was a pharmacy with few infant patients, which discontinued participation during year 4 of the project. Remaining sites were used and well accepted by the community. The WVIP remains a loyal supporter, and no problems arose with local health care providers. CONCLUSION: The model appears adaptable to urban as well as rural practice and to chain as well as independent practice in states not authorizing pharmacists to administer vaccines, for pharmacists who for other reasons prefer not to administer, and for those who prefer to offer adult immunization on a seasonal basis. From the CHD perspective, the partnership model is useful in establishing "satellite" locations to target hard-to-reach patients. Recommendations regarding agreements and responsibilities are available, as are lessons learned during project development.

Pharmacists and immunizations: a national survey.

OBJECTIVES: To obtain information about pharmacists' current involvement in and willingness to provide immunization services, and to assess perceived barriers to providing immunization services. DESIGN: Cross-sectional mail survey. SETTING: National. PATIENTS OR OTHER PARTICIPANTS: Random sample of 5,342 pharmacists from chain, independent, mass merchandiser/grocery, primary care clinic, and health maintenance organization settings. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Responses to survey on pharmacy-based immunization services--current involvement, willingness to get involved, perceived obstacles, and patients' interest. RESULTS: Three mailings yielded a response rate of 25.3% (1,348 responses). Only 53.1% of respondents knew correctly whether their state allowed pharmacists to administer immunizations. Although a significant number of pharmacists were involved in immunization activities, such as counseling and promotion, only 2.2% and 0.9% of respondents were involved in actual administration of adult and childhood immunizations, respectively. In general, men, independents, owners/partners, and pharmacists who had attended immunization-related educational programs were more willing to provide immunization services than were women, chain and staff pharmacists, and educational program nonattendees. Pharmacists who had attended immunization-related educational programs also perceived pharmacist- and patient-related factors as less problematic for pharmacy-based immunization services than did nonattendees. CONCLUSION: This survey provides a baseline measure of the nature and extent of pharmacist involvement in immunizations that can be used now and in future years. The profession can use the findings on pharmacists' willingness to provide immunization services and their perception of obstacles to such services as a basis for targeted educational and promotional programs and materials.

Endoscopic variceal sclerotherapy: experience with 30 patients.

Endoscopic sclerotherapy is used to obliterate esophageal varices in an attempt to decrease bleeding episodes. First reported in the 1940s, sclerotherapy has recently enjoyed renewed interest because surgical shunting procedures, though effective in preventing rebleeding, are associated with significant mortality and provide no increase in long-term survival. Sclerotherapy, using a flexible endoscope, has been used in 30 patients at Vanderbilt University and the VA Medical Center, Nashville, Tenn. We present our clinical experience, compare our results with those of other groups, and discuss other approaches to the management of bleeding varices.