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UCLA Older Americans Independence Center David B. Reuben, MD Center Director

UCLA Older Americans Independence Center David B. Reuben, MD Center Director. UCLA OAIC Theme. “ Preventing Disease and Disability in Vulnerable Populations: A Translational Approach ” “ Vulnerable” 1) underserved (i.e., low income, uninsured, and minorities)

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UCLA Older Americans Independence Center David B. Reuben, MD Center Director

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  1. UCLA Older Americans Independence CenterDavid B. Reuben, MDCenter Director

  2. UCLA OAIC Theme “Preventing Disease and Disability in Vulnerable Populations: ATranslational Approach” “Vulnerable” 1) underserved (i.e., low income, uninsured, and minorities) 2) at increased risk of losing independence because of chronic diseases or conditions, advanced age, or functional impairment

  3. UCLA OAIC • Addresses health disparities that vulnerable older persons face because of: • Inadequate understanding of contributors (e.g., socioeconomic status, inflammation) to health and specific illnesses (e.g., HIV, sleep disorders, depression) • Lack of effective preventive or therapeutic approaches (biomedical and behavioral), or • Inadequate ability to get needed treatment to vulnerable older populations (e.g., cultural barriers, ineffective health systems).

  4. UCLA OAIC

  5. RCDC Activities • CDAs • Co-funding with CTSI and Departments • Didactic components • Individualized training programs • Mentorship Committee (primary and 2-4 secondary mentors); meets quarterly • Academic Advancement

  6. Current RCDC CDAs Jordan Lake, MD, MSCR (3rd year CDA) Assistant Professor-Infectious Disease Mechanisms by which chronic inflammation accelerates aging processes in HIV patients Lee Jennings, MD, MSPH (1st year CDA) Assistant Professor-Geriatric Medicine Improving the quality and delivery of care for older adults with advanced illness

  7. Incidence Rate Ratios for fall-related injury (FRI) by screening response and prior claim for FRI, N=1776 *p<0.05 //Additional significant positive predictors in all models: age, comorbidity count, site

  8. Current and Future CDAs Joseph Dzierzewski, PhD (1st year CDA) Assistant Researcher GRECC - Cognitive and inflammatory responses of co-morbid sleep disordered breathing and insomnia in late life Hyong Jin Cho, MD, PhD (start CDA 7/14) Assistant Professor Psychiatry - Risks for inflammation-related depression and prevention of late-life depression

  9. PESC Activities 2 Classes of Pilots • Standard [Discontinued] • Rapid Grant Awards • Co-Funded by UCLA CTSI • Maximum 10K • PI: Jr. faculty or advanced trainee, with identified faculty mentor • Review by Core director and content experts with 4-week turn-around

  10. High Throughput Screening to Identify Hepcidin AntagonistsElizabeta Nemeth, Pilot Awardee Background • Excess hepcidin may contribute to anemia of inflammation by inhibiting iron delivery to plasma by degrading iron’s receptor, ferroportin (Fpn) • Pilot funding: conduct high throughput small molecule screen for hepcidin antagonists • Collaboration with Molecular Shared Screening Resource Core (UCLA)

  11. High Throughput Screening to Identify Hepcidin AntagonistsElizabeta Nemeth, Pilot Awardee • ~70,000 compounds screened; 2642 preliminary hits based on GFP • 2 chemically distinct groups of compounds • Cardiac glycosides (at nanomolar levels) • 3 compounds with a sulfur moiety that could interact with hepcidin’sthiol group; • fursultiamine most promising, tight binding, potent hepcidin inhibitor, specific to Fpn • Tested fursultiamine in mouse model • Not a robust antagonist in vivo • Metabolized to thiamine

  12. Research Cores Activities • Consultation(e.g., providing up to several hours of advice, reading a paper/proposal) • Short-term (e.g., up to 2-3 days of consultation, performing assays • Ongoing or long-term support (e.g., ongoing, part of the project team • Partnership on new proposals

  13. RRC Activities Identify potential recruitment sites Introductions to specific community organizations Review plans for minority recruitment Assistance with enrollment and retention Teach effective strategies for recruitment and retention of minority elders

  14. Joint CTSI-RCMAR-OAIC Project • Goal: identify best practices for recruiting Latino and African American seniors • Methods: Qualitative study with 6 focus groups (n=72) and 15 stakeholder interviews • Results: major negative experiences included • poor communication by research team • perceived lack of transparency in the recruitment process • lack of notification of study findings • failure to use appropriate language and cultural references

  15. ROC Activities • Provide support for data collection, data management, & proposal preparation • Enhance interoperability between Pepper Informatics and REDCap • Provide periodic workshops on research methods and operations

  16. ROC-supported findings Randomized trial of ER observational protocol for syncope vs usual care • PI: Benjamin Sun, MD (OAIC trainee), RC1-NIA • 15% of patients in observational protocol arm versus 90% in usual care admitted to hospital • No difference between arms for adverse events and 6-month re-admissions • Published in 2013 in Annals of Emergency Medicine; Basis for larger R01 proposal submitted through OHSU

  17. ROC-supported findings Assessment of sub-epidermal moisture to detect early skin damage in multi-ethnic sample of nursing home residents PI: Barbara Bates-Jensen, PhD, RN, R01-NINR Difference in incidence of Stage 1 pressure sores (erythema) explained by skin tone, not ethnicity Early skin damage by ethnicity and skin tone Skin tone of African-American NH residents

  18. ACEC Activities • Support junior researchers’ study design, statistical data analysis, and interpretation of findings • Assess the cost-effectiveness of successful clinical interventions • Provide training workshops on statistical, comparative effectiveness, and cost effectiveness analysis methods

  19. ACEC-Supported Findings Junior Researcher: Albert Shieh, MD Research Question: Can markers of bone resorption and formation be combined to assess bone metabolic balance? Findings (Abstract, ASBMR, Oct 2013): A bone balance index can be created by combining formation markers (BSAP, P1NP) with resorption marker (NTx) BBI = 7.0 + 0.178*BSAP + 0.070*P1NP – 0.022*weight – NTx The index is higher in post-menopausal women on hormone therapy than in those not on hormone therapy (+1.06 vs. -0.46, p<0.05) A larger index predicts greater bone density in the lumbar spine (0.07 SD increment in BMD per SD of BBI)

  20. IBC Activities • Support the analysis of inflammatory biology • Study design, proposal preparation • immunologic and genetic data generation and interpretation • Facilitate/expedite development of innovative technical approaches for inflammatory biology • Provide training in immunologic and molecular aspects of inflammatory biology

  21. Elderly depressed patients have diminished varicella zoster virus (VZV) specific immune responses to zoster vaccine, and treatment with antidepressant medication is associated with normalization of these responses IBC-Supported Findings VZV–specific Responder Cell Frequency (per 100,000 PBMC) Clin Infect Dis 2013, 56:1085-1093

  22. Among stressed family dementia caregivers (mean age= 60.5 y), brief daily yogic meditation intervention reverses the pattern of decreased IRF1-related transcription of innate antiviral response gene and increased NF-kB-related transcription of pro-inflammatory cytokines IBC-supported Findings Log2-transformed mean fold-difference ( SE) Meditation / Control in prevalence of transcription factor-binding motifs Psychoneuroendocrinology 2013, 38:348-55

  23. The Data Access Pilot Project Collaboration of PESC, ROC, and ACEC Rationale: Senior faculty have access to and in-depth familiarity with several rich but under-utilized data sets Trainees and junior faculty need for access data & need guidance to utilize it optimally Generic web sites that describe some data sets are available, but are often difficult for the naïve user to understand

  24. DAPP: Methods Research faculty interact with potential users to… Clarify research questions Discern whether a data set is a good match Mentor application to access data, if needed Guide application for funding, if required Mentor data analysis or conduct the data analysis as appropriate (requires payment for DAPP staff)

  25. DAPP: Initial Data Sets

  26. DAPP: Initial Data Sets

  27. UCLA OAIC Conclusions • 1 OAIC > 0.5 OAIC > 0.0 OAIC • Limitations in funding new pilots, providing, short-term supportand building new relationships • Must rely on established relationships and partnering on new proposals • Can still do excellent work both as an independent OAIC and collaboratively with other OAICs

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