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 evidence-based 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

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.

Respiratory Impairment in Older PersonsWhen Less Means MoreCarlos 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 MedicineVolume 126, Issue 1, Pages 49-57 (January 2013)

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-DefibrillatorsJohn 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 patient-centered 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

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

J Am Geriatr Soc, 2011

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%

A Method for Partitioning the Attributable Fraction of Multiple Time-Dependent Coexisting Risk Factors for an Adverse Health OutcomeHaiqun 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)

Am J Public Health, 2013; Stat Med & JAGS, 2012

Cont Clin Trials 2012; 33:1124-31

University of Pittsburgh

Boston University

Baylor University

UCLA

UC-San Diego

University ofFlorida

University of Washington

Yale University

Albert EinsteinNorthwestern University

University of Alabama

University of Minnesota

Clinical Site

Coordinating Center

University of Pennsylvania

Testosterone Trial12 Field Centers

N=800 – 1 yr treatment

Recruitment and Attrition in Testosterone Trial

Yale

↵

LIFE Main Study Field Centers

CA

LA FL

IL

NC

PACT

MA

N=1,635 - average FU=32.5 months

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