UCLA Older Americans Independence Center

David B. Reuben, MDCenter Director

UCLA OAIC Theme

“Preventing Disease and Disability in Vulnerable Populations:

A Translational 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

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).

UCLA OAIC

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

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

Predictor N (%) IRR for 24 months

Predicted FRI per person over 24 months

Response to Individual Screening Question (McFadden’s Adj R2=0.035)Fallen twice in past 12 months 659 (37%) 1.57 * 0.31Fallen and hurt self since last doctor’s visit 420 (24%) 1.20 0.28Afraid may fall because of balance or walking problems

1495 (84%) 1.09 0.25

Number of Positive Screening Responses (McFadden’s Adj R2=0.034)One 1166 (65%) REF 0.21Two 422 (24%) 1.33* 0.28Three 188 (11%) 1.84 * 0.38

Prior claim for FRI only (McFadden’s Adj R2=0.029)Prior FRI 198 (11%) 1.58 * 0.36

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

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

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

High Throughput Screening to Identify Hepcidin Antagonists

Elizabeta 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)

High Throughput Screening to Identify Hepcidin Antagonists

Elizabeta 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’s thiol 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

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

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

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

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

ROC-supported findingsRandomized 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

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

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Skin tone of African-American NH residents

Early skin damage by ethnicity and skin tone

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

ACEC-Supported FindingsJunior Researcher: Albert Shieh, MDResearch 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)

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

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

Clin Infect Dis 2013, 56:1085-1093

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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

The Data Access Pilot Project

Collaboration of PESC, ROC, and ACECRationale: 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

DAPP: MethodsResearch 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)

DAPP: Initial Data Sets

Study of Women's Health Across the Nation (SWAN)

Postmenopausal Estrogen/Progestin Interventions (PEPI) Study

Osteoporotic Fractures in Men (MrOS) Study Study of Osteoporotic Fractures (SOF) Rancho Bernardo Study Health and Retirement Study (HRS) Cardiovascular Health Study (CHS)

DAPP: Initial Data Sets

National Health and Nutrition Examination

Survey (NHANES) Multiethnic Study of Atherosclerosis

(MESA) Midlife in the United States (MIDUS)

Atherosclerosis Risk in Communities (ARIC) Study

Yoga for Kyphosis Trial Yoga Empowers Seniors Study (YESS)

UCLA OAIC Conclusions 1 OAIC > 0.5 OAIC > 0.0 OAIC Limitations in funding new pilots,

providing, short-term support and 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