Upload
alexander-lee-white
View
217
Download
0
Tags:
Embed Size (px)
Citation preview
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).
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 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
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
9%
37%54%
LightMediumDark
0
20
40
60
80
100
African American Asian Hispanic White
Earl
y st
age
PU
/ery
them
a in
cid
ence
(%
)
Light Medium Dark
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 Findings
Junior 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
VZ
V–s
peci
fic
Resp
onder
Cell
Frequency
(per
10
0,0
00
PB
MC
)
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: 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)
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