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Kuchibhatla M.N.,Duke University | Fillenbaum G.G.,Duke University | Fillenbaum G.G.,Geriatrics Research
American Journal Geriatric Pharmacotherapy | Year: 2011

Objective: The objective of this article was to determine whether, in drug intervention trials, growth mixture modeling (GMM) is able to identify drug-responsive trajectory classes that are not evident in traditional growth modeling approaches. Methods: We reanalyzed acute phase (biweekly data up to 7 occasions) and longitudinal (12 months) data on the 469 patients in the SADHART-CHF study of the safety and efficacy of sertraline for depression in patients with heart failure. GMM was used to identify the trajectory classes present in the treatment and placebo groups, based on Hamilton Depression Rating Scale scores. Results:Two distinct trajectory classes were identified in the treatment group: (1) chronic depressives (12%), who remained depressed through the treatment phase; and (2) responders (88%), who had scores indicating nondepression at the conclusion of the acute phase. At baseline, chronic depressives were distinguished by higher Hamilton Depression Rating Scale scores, the presence of implantable cardioverter defibrillators, and a history of anxiety. During follow-up, they were more likely to have unstable angina. Only responders remitted (70%). Three distinct trajectories were identified in the placebo group: (1) moderating depressives (19%), (2) temporary improvers (13%), and (3) responders (68%). At baseline, the classes differed in mean Hamilton Depression Rating Scale scores, responders' scores falling between the other 2 classes, and the proportion with renal disease. Only remission differed at follow-up: responders (76%), moderating depressives (21%), and temporary improvers (3%). Where the traditional analytic approach found improvement from moderate to mild depression but no significant treatment effect, GMM found response in 20% more people in the treatment group than in the placebo group. Conclusions: Unlike conventionally used, standard analytic approaches, which focus on intervention impact at study end or change from baseline to study end, GMM enables maximum use of repeated data to identify unique trajectories of latent classes that are responsive to the intervention. ClinicalTrials.gov identifier: NCT00078286. © 2011 Elsevier HS Journals, Inc. All rights reserved.

Espinoza S.E.,Gerontology and Palliative Medicine | Espinoza S.E.,University of Texas Health Science Center at San Antonio | Espinoza S.E.,Geriatrics Research | Hazuda H.P.,Clinical Epidemiology | Hazuda H.P.,University of Texas Health Science Center at San Antonio
Journal of the American Geriatrics Society | Year: 2015

OBJECTIVES: To examine the association between neighborhood residence and frailty prevalence in older Mexican Americans (MAs). DESIGN: Cross-sectional, observational study. SETTING: Socioeconomically and ethnically diverse neighborhoods in San Antonio, Texas. PARTICIPANTS: Community-dwelling older MA adults (aged ≥65) who completed the baseline examination of the San Antonio Longitudinal Study of Aging (SALSA) (1992-1996) (N = 394). MEASUREMENTS: Subjects were randomly sampled from three types of neighborhoods that varied in ethnic composition and economic environment: barrio (low-income, exclusively MA), transitional (middle-income, equal proportion MAs and European Americans (EAs)) and suburban (upper-income, predominantly EA). Frailty was classified using the Fried criteria. Frailty odds were estimated according to neighborhood using logistic regression, with the suburban neighborhood as the reference category. Covariates included age, sex, diseases, depressive symptoms, and cognitive function. RESULTS: Frailty prevalence was 15.6% in the barrio, 9.4% in the transitional neighborhood, and 3.5% in the suburbs (P = .01). After adjusting for sociodemographic characteristics and disease covariates, odds of frailty were 4.15 times as high for MAs residing in the barrio as for those residing in the suburbs (P = .03). After adjustment for depression and cognition, this association was no longer significant. Diabetes mellitus and depression accounted for the higher odds of frailty in the barrio. Although odds of frailty in the transitional neighborhood were 1.95 times as high as those in the suburbs, the difference was not statistically significant. CONCLUSION: The ethnic composition and economic environment of the neighborhoods in which MA older adults reside are strongly associated with their odds of being frail. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Pappas S.S.,University of Michigan | Leventhal D.K.,University of Michigan | Albin R.L.,University of Michigan | Albin R.L.,Geriatrics Research | Dauer W.T.,University of Michigan
Current Topics in Developmental Biology | Year: 2014

This chapter focuses on neurodevelopmental diseases that are tightly linked to abnormal function of the striatum and connected structures. We begin with an overview of three representative diseases in which striatal dysfunction plays a key role-Tourette syndrome and obsessive-compulsive disorder, Rett's syndrome, and primary dystonia. These diseases highlight distinct etiologies that disrupt striatal integrity and function during development, and showcase the varied clinical manifestations of striatal dysfunction. We then review striatal organization and function, including evidence for striatal roles in online motor control/action selection, reinforcement learning, habit formation, and action sequencing. A key barrier to progress has been the relative lack of animal models of these diseases, though recently there has been considerable progress. We review these efforts, including their relative merits providing insight into disease pathogenesis, disease symptomatology, and basal ganglia function. © 2014 Elsevier Inc.

Johnson K.S.,Duke University | Johnson K.S.,Geriatrics Research
Journal of Palliative Medicine | Year: 2013

Racial and ethnic disparities in health care access and quality are well documented for some minority groups. However, compared to other areas of health care, such as disease prevention, early detection, and curative care, research in disparities in palliative care is limited. Given the rapidly growing population of minority older adults, many of whom will face advanced serious illness, the availability of high-quality palliative care that meets the varied needs of older adults of all races and ethnicities is a priority. This paper reviews existing data on racial and ethnic disparities in use of and quality of palliative care and outlines priorities for future research. © Copyright 2013, Mary Ann Liebert, Inc. 2013.

Banerjee R.,University of Michigan | Yung R.,Geriatrics Research
Aging Cell | Year: 2014

Regulatory T-cell (Treg, CD4+CD25+) dysfunction is suspected to play a key role in immune senescence and contributes to increased susceptibility to diseases with age by suppressing T-cell responses. FoxP3 is a master regulator of Treg function, and its expression is under control of several epigenetically labile promoters and enhancers. Demethylation of CpG sites within these regions is associated with increased FoxP3 expression and development of a suppressive phenotype. We examined differences in FoxP3 expression between young (3-4 months) and aged (18-20 months) C57BL/6 mice. DNA from CD4+ T cells is hypomethylated in aged mice, which also exhibit increased Treg numbers and FoxP3 expression. Additionally, Treg from aged mice also have greater ability to suppress effector T-cell (Teff) proliferation in vitro than Tregs from young mice. Tregs from aged mice exhibit greater redox remodeling-mediated suppression of Teff proliferation during coculture with DCs by decreasing extracellular cysteine availability to a greater extent than Tregs from young mice, creating an adverse environment for Teff proliferation. Tregs from aged mice produce higher IL-10 levels and suppress CD86 expression on DCs more strongly than Tregs from young mice, suggesting decreased T-cell activity. Taken together, these results reveal a potential mechanism of higher Treg-mediated activity that may contribute to increased immune suppression with age. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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