Yale OAIC Overview
YALE OAIC Theme
Investigation of multifactorial geriatric health conditions
• single conditions resulting from multiple contributing factors
or affecting multiple health outcomes
• multiple conditions occurring simultaneously
Subtheme
• advance the science of clinical decision making in
the face of trade-offs and multiple competing outcomes
Administrative Relationships of Yale Program on
Aging and OAIC to Institution
Three geriatric conditions—muscle weakness, slow gait, and depression, were
associated with hospital admission after heart failure diagnosis, after accounting
for other relevant demographic, social, and clinical factors.
Geriatric conditions are important, and potentially modifiable, risk factors for
hospital admission in heart failure that should be routinely assessed at the time
of heart failure diagnosis.
SILVER-AMI
• NIH/NHLBI R01 HL115295
• 5 year direct costs: $7.2M
• PI: Sarwat Chaudhry, M.D., Pepper Scholar and Beeson
Scholar
• Observational study of 3000 patients 75+ years hospitalized
with acute myocardial infarction (AMI)
• Goal: develop & validate risk models for 6-month hospital
readmission, mortality, and decline in health status
• Hypothesis: currently available risk models can be improved
by incorporating geriatric conditions – impairments in
cognition, muscle strength, gait, vision & hearing
If validated in future cohorts, these
clinical features with bacteriuria plus
pyuria may serve as an evidencebased clinical definition of UTI to
assist in management decisions.
The CRANNY Study
• CRANberry capsules for prevention of UTI in Nursing homes
at Yale
• NIA-funded RCT, 05/12-04/16, total costs: $2.6M
• Primary hypothesis: 2 cranberry capsules/day will be associated
with 33% reduction in occurrence of episodes of bacteriuria
plus pyuria over 12 months, compared with placebo
• Sample size: 180
• Urine specimens obtained at baseline and every 2 months
• Urinary tract specific symptoms assessed at each time point
• Secondary outcomes: symptomatic UTI, hospitalization, death,
antibiotic prescriptions, resistant organisms
Figure
Respiratory Impairment in Older Persons
When Less Means More
Carlos A. Vaz Fragoso, MD, Thomas M. Gill, MD, Gail McAvay, PhD,
Philip H. Quanjer, MD, PhD, Peter H. Van Ness, PhD, MPH and
John Concato, MD
American Journal of Medicine
Volume 126, Issue 1, Pages 49-57 (January 2013)
A novel Z-score approach, pioneered
by Yale OAIC investigators, is more
clinically meaningful in identifying
older persons with respiratory
impairment (including COPD) than
GOLD, the current standard.
Eur Respir J, 2012; Am J Med, 2012;
Am J Med, 2013
2012
Aging Lung Initiative
• LIFE Study
– Spirometry Reading Center
– Blood RNA Biorepository: R01 under review
• NIA Program Project application
– to investigate the pathogenesis, prevention,
and treatment of COPD
Patient Preferences for Deactivation of Implantable Cardioverter-Defibrillators
John A. Dodson, MD; Terri R. Fried, MD; Peter H. Van Ness, PhD, MPH; Nathan E. Goldstein, MD; Rachel Lampert, MD
JAMA Intern Med; Volume 173, Issue 5, Pages 377-379 (March 11, 2013)
In a survey of 95 patients with implantable cardioverter-defibrillators (ICD),
Yale OAIC investigators evaluated preferences for ICD deactivation.
When faced with a series of 5 scenarios about deactivation, 71% of respondents
(mean age, 71.4 y) answered “possibly” or “definitely yes” that they would want
their ICD deactivated.
The respondents demonstrated relatively poor understanding of the risks and
benefits of the ICD.
These findings highlight the importance of incorporating multiple patientcentered outcomes into advance care planning for ICD patients.
New Pepper Scholars
• Kasia Lipska, MD (Endocrinology)
– decision-making and management in older persons with diabetes
– 2013 GEMSSTAR recipient
• Raimund Herzog, MD (Endocrinology)
– role of multiple peripheral metabolites on cognitive performance
– NIDDK K08 recipient
• Joan Monin, PhD (Chronic Disease Epidemiology)
– multiple chronic conditions and mutuality of care in late life marriage
– 2013 NIA K01 recipient
• Terrance Murphy, PhD (Geriatrics, Biostatistics Core)
– Bayesian joint models of the time-dependent confounding between
multiple medications and manifestations of delirium
Recent/New Pilot Projects
• Ifat Levy, PhD (Comparative Medicine and Neurobiology)
– using behavioral economics and fMRI to develop a tool for the
assessment of ambiguity aversion in medical decision making
• Frank Slack, PhD (Molecular, Cellular & Developmental Biology)
– using data and specimens from BLSA to identify miRNAs that
could serve as biomarkers of longevity and aging in humans
• Carlos Vaz Fragoso, MD (Geriatrics)
– Dyspnea in Older Persons: A Multifactorial Geriatric Health Condition
• Gerald Shadel, PhD (Pathology and Genetics)
– Multifactorial Nature of Age-Related Hearing Loss in a Mouse Model
of Mitochondrial Pathology
Basic and Translational Program
in Immunology of Aging
• NIAID Contract: Impaired Human Innate Immune Cell Function in the Elderly
and Immunosuppressed
(E. Fikrig PI; A. Shaw and R. Montgomery Project Leaders)
– elucidating age-related changes in human Toll-like receptor function
• U19 AI: Immune Responses Defining Efficiency of Influenza Immunization
(A. Shaw Project Leader)
– project within Yale-based Center of the NIAID Human Immunology
Project Consortium (D. Hafler PI)
– computational biology approaches to influenza vaccine response
signatures in young, older and frail adults
• R01AG: Mechanisms of Dysregulated Immunity with Aging (D. Goldstein PI)
– evaluating relationship between NKT cell inflammation and dendritic cell
dysfunction in aged mice
Basic and Translational Program
in Immunology of Aging
• R01AG: Aging and IL-7-mediated CD8 T Cell Survival (I. Kang PI)
– investigating age-associated expansion of novel population of effector
memory CD8 T cells in mouse models
• U19 application: Innate and Adaptive Immune Control of Influenza Infection
in Mice and Humans (A. Iwasaki PI; A. Shaw Human Subjects Core Leader)
– will investigate age-associated changes in lung microbiome and in
influenza-specific lung resident memory T cells in aged mice and
older adults
• R01 application: Circadian Rhythms and Immune Responses in Aging
(R. Montgomery and A. Shaw PIs)
– will investigate circadian variation in TLR function in aged humans and
mice
J Am Geriatr Soc, 2011
gerontological research is characterized by a
number of challenges, such as missing data,
recurrent events, multiple competing outcomes,
and multifactorial interventions, all of which make
its statistical analysis inherently complex
A Method for Partitioning the Attributable Fraction of Multiple TimeDependent Coexisting Risk Factors for an Adverse Health Outcome
Haiqun Lin, MD, PhD, Heather G. Allore, PhD, Gail McAvay, PhD, Mary E. Tinetti, MD, Thomas M. Gill, MD, Cary P. Gross, MD,
and Terrence E. Murphy, PhD
American Journal of Public Health; Volume 103, Issue 1, Pages 177-182 (January 2013)
Yale OAIC investigators developed and successfully implemented the longitudinal
extension of the average attributable fraction (LE-AAF), which decomposes the total
contributions of coexisting time-varying risk factors (e.g. diseases) on a timed occurrence
of an outcome (e.g. death, hospitalization) into additive contributions from each risk factor
whose sum is between 0 and 100%
Am J Public Health, 2013; Stat Med & JAGS, 2012
Cont Clin Trials 2012; 33:1124-31
Testosterone Trial
12 Field Centers
University of Washington
Boston University
Yale University
Albert Einstein
University of Minnesota
Northwestern University
University of Pittsburgh
UCLA
University of
Pennsylvania
University of Alabama
UC-San Diego
Baylor University
Coordinating Center
Clinical Site
N=800 – 1 yr treatment
University of
Florida
Recruitment and Attrition in Testosterone Trial
Yale
↵
LIFE Main Study Field Centers
CA
PA
IL
NC
LA
FL
N=1,635 - average FU=32.5 months
MA
CT
LIFE Determination of Major Mobility Disability at 24 months

Yale
Future Directions
•
•
•
•
•
Roybal Center
Shock Center application
LIFE-ARISE prevention of AD
Multi-Modality Mobility Trial
EASE-HF