YALE UNIVERSITY
Claude D. Pepper Older Americans Independence Center

Thomas M. Gill, M.D.
Principal Investigator
  203-688-9423   thomas.gill@yale.edu
Mary Geda
Program Administrator
  203-737-1800   mary.geda@yale.edu
     
CENTER DESCRIPTION

The overarching mission of the Yale Older Americans Independence Center (OAIC), established in 1992, is to provide intellectual leadership and innovation for aging research that is directed at enhancing the independence of older persons. The unifying theme of the Yale OAIC is the investigation of multifactorial geriatric conditions, encompassing single conditions resulting from multiple contributing factors or affecting multiple outcome domains and multiple conditions occurring simultaneously.

The central Yale OAIC hypothesis is that geriatric conditions are determined by the co-occurrence of multiple predisposing and precipitating factors. These conditions and factors, in turn, affect a range of health outcomes. The predisposing factors may be at the genetic, molecular, physiologic, impairment, disease, or socio-demographic level, while the precipitating factors may be behavioral, environmental, social, medical, or psychological. The Yale OAIC theme requires designs and models (e.g. molecular, animal, and statistical) that inform the study of multiple, simultaneously interactive factors and outcomes. As a prominent subtheme, the Yale OAIC also aims to advance the science of clinical decision making in the face of trade-offs and multiple competing outcomes. This includes developing strategies to elicit older persons’ health outcome priorities.

The Specific Aims of the Yale OAIC are to

  1. Foster the career development of future academic leaders, from multiple disciplines, in aging research;
  2. Train investigators, biostatisticians and other methodologists in the skills necessary to design, conduct, analyze, and disseminate findings from studies of multifactorial geriatric conditions;
  3. Develop and disseminate design and analytic techniques for conducting studies of multifactorial geriatric conditions;
  4. Develop strategies for recruiting into, and retaining, a broad spectrum of older persons, including minorities, into studies of multifactorial geriatric conditions;
  5. Investigate the causative mechanisms of, and develop and test effective treatments for, geriatric conditions from a multifactorial research perspective;
  6. Develop strategies to enhance clinical decision making in the setting of multiple competing outcomes;
  7. Encourage and facilitate interdisciplinary research (basic, translational and clinical) that connects to our focus on multifactorial geriatric conditions; and further strengthen collaborations with other OAICs.

The Yale OAIC cores include: 1) Leadership and Administrative; 2) Research Education; 3) Pilot/Exploratory Studies; 4) Operations; and 5) Biostatistics.


CORES
Leadership and Administrative Core (LAC)
Leader 1:    Thomas M. Gill, MD   thomas.gill@yale.edu
Leader 2:    Terri Fried, MD   terri.fried@yale.edu
Leader 3:    Denise Acampora, MPH   denise.acampora@yale.edu
Leader 4:    Mary Geda, RN, BSN, MSN   mary.geda@yale.edu
The overarching objective of the Leadership and Administrative Core (LAC) is to advance the scientific knowledge base of multifactorial geriatric conditions. The LAC, which is led by two board-certified geriatric physician investigators with complementary expertise, is responsible for strategic planning, organization, administrative operations and evaluation of the OAIC research and training program. A special effort is devoted to ensuring the cohesion of the Center and maintenance of an interdisciplinary and translational research focus on the common research theme, which is "the investigation of multifactorial geriatric conditions". The key LAC tasks are achieved by the LAC leadership administrators, and three committees: the Executive Committee, the Internal Advisory Committee, and the External Advisory Committee.

Research Education Component (REC)
Leader 1:    Terri Fried, MD   terri.fried@yale.edu
Leader 2:    Albert Shaw, MD PhD   albert.shaw@yale.edu
Leader 3:    Denise Acampora, MPH   denise.acampora@yale.edu
Leader 4:    Andrew Cohen, MD, DPhil   andrew.b.cohen@yale.edu
The objective of the Research Education Core (REC) is to identify highly promising early-stage investigators and provide support to promote their development as independent investigators and leaders in aging research. The REC seeks to provide three groups of investigators, designated as Pepper Scholars, Small REC Awardees, and REC Affiliates, with the knowledge and skills to conduct biological, translational, and clinical studies of multifactorial geriatric conditions and to obtain subsequent funding from a broad range of sources. The outcomes and career advancement goals for the Pepper Scholars include: 1) publication of research results in high-impact journals; 2) success in obtaining independent funding, both to support further career development (e.g. K08 and K23 awards) and specific projects (e.g. R21 and R01 awards); and 3) development of leadership skills necessary to manage research teams and to become successful mentors themselves.

Pilot and Exploratory Studies Core (PESC)
Leader 1:    Albert Shaw, MD PhD   albert.shaw@yale.edu
Leader 2:    Terri Fried, MD   terri.fried@yale.edu
Leader 3:    Denise Acampora, MPH   denise.acampora@yale.edu
The primary goal of the Pilot/Exploratory Studies Core (PESC) is to facilitate the development of innovative and rigorous research studies that will enhance our understanding of the pathogenesis, etiology, diagnosis, prevention, and management of multifactorial geriatric conditions, leading ultimately to the development of efficacious and cost-effective interventions to increase or maintain the independence of older Americans.

Operations (RC1)
Leader 1:    Katy Araujo, MPH   katy.araujo@yale.edu
Leader 2:    Mary Geda, RN, BSN, MSN   mary.geda@yale.edu
Leader 3:    Lauren Ferrante, M.D., M.H.S.     lauren.ferrante@yale.edu
The Operations Core (OC) supports OAIC investigations of multifactorial geriatric conditions by recruiting and retaining diverse populations of older persons, seeking input from the local community in research, planning and dissemination, monitoring participant safety, ensuring regulatory compliance, developing surveys and instruments, designing Information Technology (IT) systems to implement research, collecting and preparing data for statistical analysis, and providing continuity and shared knowledge across projects. The overall goal of the OC is to ensure the successful implementation of research focused on multifactorial geriatric conditions. This goal will be accomplished by leading, managing, and coordinating the effective, efficient and innovative use of facilities, data, staff, resources, and space. There is a consistent demand for experienced personnel with the ability to quickly execute aging-focused research and an increasing need for informatics skills and technology to streamline work.

Biostatistical Design and Analysis Core (RC2)
Leader 1:    Denise Esserman, PhD   denise.esserman@yale.edu
Leader 2:    Brent Vander Wyk, PhD   brent.vanderwyk@yale.edu
The overarching goals of the Biostatistics Core (BC) are to provide design and analytical services to OAIC investigators conducting studies of multifactorial geriatric conditions; to develop and disseminate new design and analytical techniques for conducting studies with older persons; and to train a cadre of clinical investigators, biostatisticians, and epidemiologists in the skills necessary to design, conduct, and analyze gerontologic studies.

CAREER DEVELOPMENT
REC Scholar, Research & Grants Funded During Pepper Supported Time Years /
Publications
 
Edward Manning
Instructor / Yale University
Aging of the Human Pulmonary Artery: Analyzing Gene Expression to Tissue
There is a knowledge gap in the underlying mechanisms of how the pulmonary artery changes with age. Evidence from an aging mouse model shows that pulmonary arteries stiffen with an age. Pulmonary arterial stiffening in humans is associated with lung diseases including chronic obstructive pulmonary disease, pulmonary hypertension, and disease associated with dyspnea; dyspnea occurs in over 10 million Americans over the age of 65. Yet, the association between age and pulmonary arterial stiffening is poorly described. Dyspnea is associated with frailty and poor health in the older population, but the etiology of dyspnea in many of these older individuals is unexplained. Therefore, this study aims to identify an association between age and pulmonary arterial stiffness in the human pulmonary artery and investigate underlying mechanisms of human pulmonary arterial stiffening. These aims are based on findings from a mouse model of pulmonary arterial aging and will employ similar investigational techniques as those successfully used in the mouse model. The first aim is to characterize the association of material stiffness of the pulmonary artery with age by mechanically testing 20 disease-free pulmonary arteries from deceased human donors ranging from 18 to 80 years old. Material stiffness will be calculated from measurements of deformation of the pulmonary arteries, including diameter, pressure, and force, while mounted on cannulas and submerged in physiologic solution. An additional aim is to use 2-photon imaging of 20 disease-free pulmonary arteries from deceased human donors ranging from 18 to 80 years old to characterize the association of extracellular collagen fiber orientation with age. The orientation of collagen fibers will be calculated from using 2-photon imaging and fast fourier transform analysis. The final aim is to identify whether pulmonary arterial cell gene expression changes as a function of age by performing single cell RNA sequencing on 20 disease-free pulmonary arteries from deceased human donors ranging from 18 to 80 years old. This aim will be accomplished by performing single cell RNA sequencing, a unique tool to investigate cell populations in tissue with near complete genomic profile of individual cells. These cellular specific changes of genetic expression will identify multiple cellular pathways and mechanisms responsible for changes in the pulmonary artery as a function of age. This study will be the foundation for future clinical investigations to associate age-related pulmonary arterial stiffness and health outcomes. Additionally, a better understanding of underlying mechanisms related to increased pulmonary arterial stiffening will provide information to determine optimal non-invasive measurements of pulmonary arterial stiffening in clinical settings and potential therapeutic targets for slowing or reversing the aging process of the pulmonary artery in future studies.
2021-2023 /
2 (total)
1 (1st/Sr)
 
Cameron Gettel
Assistant Professor / Yale University
Development and validation of the Patient-Reported Outcome Measure – Older adult care Transitions from the Emergency Department (PROM-OTED) tool
Persons aged 65 years and older account for over 22 million emergency department (ED) visits annually. Recent efforts to reduce unnecessary hospitalizations following ED evaluation have resulted in approximately 65% of older adult ED patients being discharged home. This vulnerable time period post-ED discharge has significant clinical and public health importance as it has been associated with an increased likelihood of morbidity and mortality as well as unscheduled ED recidivism and hospital admission. Despite high rates of adverse outcomes in this period of transition, little is known regarding the experiences and specific challenges faced by older adults during transitions home from the ED. Having a clear understanding of patients’ priorities regarding health-related quality of life, functional disability, communication barriers, and condition-specific symptoms after ED discharge is essential to inform clinical conversations and the development of interventions targeting care transitions for older adults. The overall objective of this proposal is to use a sequential exploratory mixed-methods approach to develop and validate the Patient Reported Outcome Measure - Older adult care Transitions from the ED (PROM-OTED) tool, a novel care transitions PROM for older persons experiencing ED discharge care transitions. We will achieve this objective with the following two aims: 1) To develop the PROM-OTED tool, characterizing outcomes of ED discharge care transitions prioritized by older persons. We will use an iterative qualitative approach including concept development, item generation, member checking, cognitive debriefing, and expert panel item-reduction by a modified Delphi process; and 2) To conduct internal validity testing of the PROM-OTED tool. We will perform quantitative survey evaluation of the tool’s initial psychometric properties and feasibility among older persons who recently experienced an ED discharge care transition. Specifically, this work will have significant impact by developing a measure to assess whether outcomes prioritized by older adults experiencing ED discharge care transitions are currently met and identify opportunities for improvement in the clinical and research arenas. Findings of this proposal will improve our understanding of the needs of an aging society to inform intervention development and policy decisions. During the award period, the candidate will acquire relevant skills and benefit from mentorship by accomplished clinician-researchers with complementary skill sets. This investigation will serve as preliminary work towards a future NIA K award application, in line with the candidate’s long-term objectives of assessing the PROM-OTED tool in a larger national ED sample, including those with Alzheimer’s disease and related dementias (ADRD), and subsequently developing care transition interventions to help older adults successfully navigate ED discharge care transitions.
  • ARCOM-22-878456

2021-2023 /
3 (total)
1 (1st/Sr)
 
Gregory Ouellet
Assistant Professor / Yale University
Does it still help? Benefits, harms, and surrogates’ perspectives about anticoagulation in patients with atrial fibrillation and advanced dementia
Specific Aims: Aim 1: To examine the association between oral anticoagulant use with mortality and stroke risk reduction in older adults with advanced dementia and atrial fibrillation. Aim 2: To examine the association between oral anticoagulant use and serious bleeding events in older adults with advanced dementia and atrial fibrillation. Aim 3. To understand how surrogate decision-makers of individuals with atrial fibrillation and dementia perceive decisions about anticoagulation when presented with the empiric evidence of benefits and harms generated by this project.
2020-2022 /
12 (total)
5 (1st/Sr)
 
Zachary Levine
Assistant Professor of Pathology and Molecular Biophysics and Biochemistry / Yale University
Deducing the Intersection between Type II Diabetes and Cellular Senescence
Cellular senescence is one of the major hallmarks of aging and is presumed to play a causal role in age-related pathogenesis. Given that cellular senescence is often accompanied by increased pro-inflammatory activity, the accumulation of senescent cells in the endocrine and central nervous system likely drives inflammation and neurodegeneration over the life course. Given that over 30 million Americans (roughly 10% of the US population) have diabetes, it is urgent to understand how diabetes affects human aging, especially since increased rates of aging are associated with shorter lifespans and staggering increases in morbidity. In order to test this association, a molecular understanding of how soluble amyloids form and interact with pancreatic ß -cells must be established. In this proposal, Dr. Levine focuses on Islet Amyloid Polypeptide (IAPP), an endocrine amyloid protein co-secreted with insulin in T2D, and which contributes to ß-cell death in its aggregated form.
2020-2022 /
11 (total)
0 (1st/Sr)
 

Past Scholars
Xi Chen, Yale University (2016-2020)
Guido Falcone, Yale University (2017-2020)
Morgan Levine, Yale University (2018-2020)
Joan Monin, Yale University (2018-2020)
Janice Hwang, Yale University (2018-2020)
Brienne Miner, Yale University (2019-2021)
Maor Sauler, Yale University (2019-2021)

PILOT/EXPLORATORY PROJECTS (10 Pilot Projects Listed)
1. Project Title: Does it still help? Benefits, harms, and surrogates’ perspectives about anticoagulation in patients with atrial fibrillation and advanced dementia: REC (2020-2022)
  Leader: Gregory Ouellet
 

Dementia affects 5.5 million U.S. adults 65 and older; almost 20% of them have atrial fibrillation, which significantly increases stroke risk. A critical decision is whether to prescribe an oral anticoagulant to reduce this risk. Current guidelines, derived from trials that largely excluded individuals with dementia, recommend weighing the tradeoff between the risk of stroke without treatment using the CHA2DS2VASc score and the risk of bleeding with treatment. Nearly all patients with both atrial fibrillation and dementia meet the threshold for anticoagulation due to their age and comorbidities. However, considering tradeoffs for individuals with dementia is more complex, both because of lack of evidence and the potential for dementia to modify the magnitude of the potential benefits and harms.

The balance of benefits and harms of anticoagulation likely shifts over the course of dementia. As dementia progresses, there is less function to lose and life expectancy shortens, attenuating potential benefits. Our preliminary data, however, suggests that many individuals with advanced dementia and atrial fibrillation receive anticoagulants in the last six months of life. At this point, no formal studies have quantified the benefits and harms associated with anticoagulation in this population. Furthermore, the factors that surrogate decision-makers consider important when deciding about anticoagulation are not known. This information is critical, as surrogates may place value on additional outcomes which are not easily quantified, or may consider very modest benefits, if found, to be important. As a first step in optimizing atrial fibrillation treatment in persons with dementia, this work will investigate two factors critical to anticoagulant prescribing decisions: 1) empiric evidence of outcomes in those most severely affected by dementia and 2) the perspectives of surrogate decision-makers.

To begin building evidence that quantifies changing benefits and harms of anticoagulation over the course of dementia, this study will investigate whether anticoagulation retains a net benefit even among those with advanced dementia. Linking data from the Minimum Data Set, an assessment of nursing home patients, and Medicare claims will facilitate tracking longitudinal associations between anticoagulant use and the outcomes of death, stroke, and bleeding. Our hypothesis is that bleeding harms will exceed measurable reductions in mortality and stroke. As persons with dementia often live with prolonged incapacity (i.e., they are unable to make healthcare decisions), it is also critical to investigate the perspectives of surrogate decision-makers, who may or may not change their perspectives on anticoagulation for their loved one based on the evidence generated by this study. To accomplish this goal, surrogate decision-makers will be recruited from a large academic dementia care practice and local nursing homes for in-depth qualitative interviews.

The results of this work are critical to improving anticoagulation prescribing for atrial fibrillation among individuals with dementia. A Pepper Scholar Award will provide Dr. Ouellet the necessary training and mentorship to complete this important work and to make continued progress towards an independent career focused on decision-making at the interface of dementia and multimorbidity.

 
2. Project Title: Deducing the Intersection between Type II Diabetes and Cellular Senescence: REC (2020-2022)
  Leader: Zachary Levine
  While there are multiple hallmarks of human aging that cover a wide variety of genomic, epigenomic, metabolomic, and proteomic changes, many of these hallmarks are likely interconnected to one another. The confluence of aging hallmarks has historically been unclear, however deducing common threads that drive multiple hallmarks of aging would be a significant asset for understanding and intervening in age-related diseases and dysfunction. Knowledge of these determinants could greatly enhance clinical diagnoses of older Americans and reduce the number of comorbidities that accompany human aging. In this proposal, we investigate two hallmarks of aging, namely a loss in proteostasis and cellular senescence. We propose that a putative driver of both these hallmarks includes the aggregation of soluble amyloid oligomers, but not insoluble fibrils. To do this, we focus on models of Type II Diabetes, where the misfolding and soluble aggregation of Islet Amyloid Polypeptides results in the degenerative loss of insulin secreting b-cells and pancreatic dysfunction. Soluble amyloid oligomers are also one of the primary drivers of cellular senescence in fibroblasts and mesenchymal stem cells, however their ability to induce cellular stress and pancreatic senescence is less well understood. Using a combination of molecular modeling, solution biophysics techniques (spectroscopy and fluorescence microscopy), and a combination of biomarker and epigenetic measures, we will investigate the intersection of Type II Diabetes-induced loss of proteostasis and cellular senescence in pancreatic b-cells. We hypothesize that the same soluble amyloid species that degrade pancreatic islet cells are also potent inducers of cellular senescence, identifying a common pharmacophore that affects multiple hallmarks of aging. Targeting of soluble amyloids through peptidomimetic compounds will also be tested, and the degree to which the soluble amylome can be modulated in order to mitigate multiple age-related processes at once. Successful completion of this proposal would highlight the intersection of multiple hallmarks of aging from a biophysical, chemical, and biological point of view. These results would also inform clinical models of disease and could lead to the use of senolytics for mitigating diabetes, or diabetes medications (e.g. metformin) for slowing biological aging. These results could also extend to other age-related pathologies such as Alzheimer’s Disease and Parkinson’s Disease, which are also accompanied by soluble amyloid species that likely enhance cellular senescence and premature biological aging. The need to better understand multifactorial contributions to human aging is essential and represents a challenge that must be met in the 21st century. By bridging knowledge from complimentary fields in physics, biology, and medicine, a cohesive theory of aging can be constructed that transcends individual hallmarks of aging, leading to treatments that target the biology of aging itself versus latent phenotypes that are often beyond intervention or rescue.
 
3. Project Title: The Feasibility of the Voices Digital Health Tool for Elder Mistreatment Screening in the Primary Care Setting: PESC (2021-2022)
  Leader: Fuad Abujarad
  Elder mistreatment is a deeply problematic social and medical issue that has received inadequate attention. The Centers for Disease Control and Prevention defines elder mistreatment as “the intentional act, or failure to act, by a caregiver or trusted person that causes or creates a risk of harm to an adult age 60 or older”. There are six commonly reported categories of elder mistreatment: physical abuse, financial exploitation, emotional abuse, sexual abuse, neglect, and abandonment. The prevalence of mistreatment in the United States is estimated to be 10% of community?dwelling older adults. Elder mistreatment causes serious adverse outcomes for its victims including injury, increased service utilization, mental distress, and increased mortality. A major barrier in overcoming elder mistreatment is the inability to accurately identify victims. It is estimated that only 1 in 24 cases become known to authorities. This is problematic as older adults are not likely to report that they are being mistreated. Working with leading experts in elder mistreatment, geriatrics, user experience research, and digital health, our team developed the digital health tool VOICES to screen and identify suspicion of elder mistreatment. VOICES is a user-friendly, self-administrated, tablet-based tool used by older adults to screen for elder mistreatment. The VOICES tool utilizes virtual coaching, interactive multimedia libraries (e.g., graphics, video clips, animations, etc.), and brief motivational interviewing designed to enhance identifying mistreatment among older adults. We have completed the development of the VOICES tool and piloted it with older adults in a challenging and busy emergency department settings. We were able to successfully establish a proof of concept and feasibility of our tool. Among the 230 subjects who used VOICES so far, 18 older adults wanted to self-report EM after using VOICES and requested help from the social workers. There is an opportunity to expand and test VOICES in broader and wider-reaching healthcare settings, specifically in primary care. In this project we will conduct a feasibility study (N= 80) examining the use of the VOICES tool to screen for elder mistreatment by older adults in primary care settings. This pilot project, if funded, will allow us to examine the feasibility of our complex intervention in the primary care settings. We expect this project will lead to a future comparative effectiveness study comparing (VOICES + in-person screening) to the standard-of-care (in-person screening).
 
4. Project Title: Genetic Predisposition to Cardiovascular Disease and Risk of Death, Dementia and Disability in Older Persons: PESC (2021-2022)
  Leader: Guido Falcone
  Statins constitute a powerful treatment for hyperlipidemia, one of the most important risk factors for cardiovascular disease (CVD). While the benefit of statins in primary prevention has been clearly established for middle-aged persons, there is no definitive evidence supporting their use in older adults. The PREVENTABLE clinical trial will enroll 20,000 older adults to test the hypothesis that statins increase survival free of dementia or disability in persons aged >75 years without clinically-evident CVD. Through the support of this Yale Pepper Pilot Award, we will evaluate whether a higher genetic predisposition to CVD increases the risk of this composite outcome in this age group. The results from this pilot study will provide key preliminary data to support an R01 application for an ancillary genetic study to PREVENTABLE that will test the hypothesis that information on known genetic risk factors for CVD can identify persons aged >75 who may preferentially benefit from statin treatment. Genomic information is emerging as a powerful precision medicine tool to identify persons at highrisk of human disease. There are numerous genetic risk variants that contribute to the pathophysiological processes that lead to the endpoints evaluated by PREVENTABLE. These genetic variants constitute an excellent basis for developing precision medicine tools, as they remain constant throughout life and immune to confounding by post-natal exposures due to their random assignment during meiosis. While promising, the field still lacks evidence on whether these genetic risk factors retain their effect and predictive ability in older adults, a crucial prerequisite to explore genomic-based precision medicine strategies in this age group. We will address this knowledge gap by evaluating the role of genetic predisposition to CVD in determining the risk of death, dementia or disability in persons aged >75 years without clinically-evident CVD. We will harmonize, quality control and analyze clinical and genetic data from 95,541 persons aged >75 years enrolled in the Health and Retirement Study and the UK Biobank to pursue the following specific aims: (1) Determine whether a higher genetic predisposition to CVD is associated with higher composite risk of death, dementia and disability (primary PREVENTABLE endpoint) in persons aged >75 years without clinically-evident CV disease; and (2) determine whether a higher genetic predisposition to CVD is associated with a higher composite risk of acute myocardial infarction, stroke or death of any cause (secondary PREVENTABLE outcome) in persons aged >75 years without clinically-evident CVD. The proposed research will significantly advance our understanding of the role of high genetic predisposition to CVD in determining death, dementia, disability and acute vascular events in older adults without clinically-evident CVD.
 
5. Project Title: Improving the Tolerability and Efficacy of Allogenic Hematopoietic Stem Cell Transplant by Metabolic Modulation in Mice: PESC (2021-2022)
  Leader: Rachel Perry
  Allogeneic hematopoietic stem cell transplant (ASCT) is the current curative standard of care for treatment of certain patients with leukemia. Leukemia is most commonly diagnosed in elderly individuals, with the mean age at diagnosis with leukemia between 60 and 70 years old. Unfortunately, elderly individuals are well-known to respond more poorly to ASCT than their younger counterparts, exhibiting both reduced immune reconstitution, and increased susceptibility to graft vs. host disease (GvHD). As aging is inextricably linked to an increased risk of leukemia, it is crucial to understand the mechanisms by which elderly individuals are predisposed to impaired immune reconstitution and to GvHD, in order to better facilitate their response to curative therapy. In this proposal, we will probe this mechanism, and test a novel approach to improve immune reconstitution using fibroblast growth factor-21 (FGF-21) analog PF-05231023 in aging mice. FGF-21 analogs have been shown effective at improving metabolic health in multiple clinical trials across the lifespan; however, to our knowledge, neither clinical nor preclinical studies have explored the impact of these agents on immune reconstitution or GvHD following ASCT. Therefore, this proposal will bring to bear the PI’s longstanding expertise in metabolic physiology and pathophysiology in rodents, with the mentorship of Drs. Vishwa (Deep) Dixit (an expert in FGF-21 biology), and Stuart Seropian (a hematologist/oncologist with substantial clinical experience in ASCT, who will advise regarding the clinical implications of the studies), and could identify a new therapeutic target following ASCT in elderly patients. As FGF-21 analogs are already in advanced clinical development, these results could quickly be translated to the clinic as an adjunct before ASCT in collaboration with colleagues at the Yale Claude D. Pepper Center and the Yale Cancer Center
 
6. Project Title: Development and validation of the Patient-Reported Outcome Measure – Older adult care Transitions from the Emergency Department (PROM-OTED) tool: REC (2021-2023)
  Leader: Cameron Gettel
  Persons aged 65 years and older account for over 22 million emergency department (ED) visits annually. Recent efforts to reduce unnecessary hospitalizations following ED evaluation have resulted in approximately 65% of older adult ED patients being discharged home. This vulnerable time period post-ED discharge has significant clinical and public health importance as it has been associated with an increased likelihood of morbidity and mortality as well as unscheduled ED recidivism and hospital admission. Despite high rates of adverse outcomes in this period of transition, little is known regarding the experiences and specific challenges faced by older adults during transitions home from the ED. Having a clear understanding of patients’ priorities regarding health-related quality of life, functional disability, communication barriers, and condition-specific symptoms after ED discharge is essential to inform clinical conversations and the development of interventions targeting care transitions for older adults. The overall objective of this proposal is to use a sequential exploratory mixed-methods approach to develop and validate the Patient Reported Outcome Measure - Older adult care Transitions from the ED (PROM-OTED) tool, a novel care transitions PROM for older persons experiencing ED discharge care transitions. We will achieve this objective with the following two aims: 1) To develop the PROM-OTED tool, characterizing outcomes of ED discharge care transitions prioritized by older persons. We will use an iterative qualitative approach including concept development, item generation, member checking, cognitive debriefing, and expert panel item-reduction by a modified Delphi process; and 2) To conduct internal validity testing of the PROM-OTED tool. We will perform quantitative survey evaluation of the tool’s initial psychometric properties and feasibility among older persons who recently experienced an ED discharge care transition. Specifically, this work will have significant impact by developing a measure to assess whether outcomes prioritized by older adults experiencing ED discharge care transitions are currently met and identify opportunities for improvement in the clinical and research arenas. Findings of this proposal will improve our understanding of the needs of an aging society to inform intervention development and policy decisions. During the award period, the candidate will acquire relevant skills and benefit from mentorship by accomplished clinician-researchers with complementary skill sets. This investigation will serve as preliminary work towards a future NIA K award application, in line with the candidate’s long-term objectives of assessing the PROM-OTED tool in a larger national ED sample, including those with Alzheimer’s disease and related dementias (ADRD), and subsequently developing care transition interventions to help older adults successfully navigate ED discharge care transitions.
 
7. Project Title: Aging of the Human Pulmonary Artery: Analyzing Gene Expression to Tissue: REC (2021-2023)
  Leader: Edward Manning
  There is a knowledge gap in the underlying mechanisms of how the pulmonary artery changes with age. Evidence from an aging mouse model shows that pulmonary arteries stiffen with an age. Pulmonary arterial stiffening in humans is associated with lung diseases including chronic obstructive pulmonary disease, pulmonary hypertension, and disease associated with dyspnea; dyspnea occurs in over 10 million Americans over the age of 65. Yet, the association between age and pulmonary arterial stiffening is poorly described. Dyspnea is associated with frailty and poor health in the older population, but the etiology of dyspnea in many of these older individuals is unexplained. Therefore, this study aims to identify an association between age and pulmonary arterial stiffness in the human pulmonary artery and investigate underlying mechanisms of human pulmonary arterial stiffening. These aims are based on findings from a mouse model of pulmonary arterial aging and will employ similar investigational techniques as those successfully used in the mouse model. The first aim is to characterize the association of material stiffness of the pulmonary artery with age by mechanically testing 20 disease-free pulmonary arteries from deceased human donors ranging from 18 to 80 years old. Material stiffness will be calculated from measurements of deformation of the pulmonary arteries, including diameter, pressure, and force, while mounted on cannulas and submerged in physiologic solution. An additional aim is to use 2-photon imaging of 20 disease-free pulmonary arteries from deceased human donors ranging from 18 to 80 years old to characterize the association of extracellular collagen fiber orientation with age. The orientation of collagen fibers will be calculated from using 2-photon imaging and fast fourier transform analysis. The final aim is to identify whether pulmonary arterial cell gene expression changes as a function of age by performing single cell RNA sequencing on 20 disease-free pulmonary arteries from deceased human donors ranging from 18 to 80 years old. This aim will be accomplished by performing single cell RNA sequencing, a unique tool to investigate cell populations in tissue with near complete genomic profile of individual cells. These cellular specific changes of genetic expression will identify multiple cellular pathways and mechanisms responsible for changes in the pulmonary artery as a function of age. This study will be the foundation for future clinical investigations to associate age-related pulmonary arterial stiffness and health outcomes. Additionally, a better understanding of underlying mechanisms related to increased pulmonary arterial stiffening will provide information to determine optimal non-invasive measurements of pulmonary arterial stiffening in clinical settings and potential therapeutic targets for slowing or reversing the aging process of the pulmonary artery in future studies.
 
8. Project Title: Evaluating Antibiotic Prescribing in Homebound Veterans: small REC (2021-2022)
  Leader: Rupak Datta
  A growing number of older adults in the United States are homebound: they rarely leave home or leave home only with assistance or significant difficulty. Because such persons have limited mobility, multiple chronic conditions, and often repeated hospitalizations, homebound persons incur high risk of infection. Homebound persons also face unique challenges to the diagnosis and treatment of infection. Currently, it is unknown how often antibiotics are prescribed in homebound persons and to what extent prescribing decisions adhere to standards of care for common clinical syndromes such as urinary tract infection. There is a need to study antibiotic prescribing in homebound persons to reduce harms associated with antibiotics such as antibiotic resistance, one of the greatest health challenges of our time. Work by the candidate suggests that antimicrobial stewardship programs may offer guidance regarding antibiotic prescribing in older adults with complex illnesses. The current proposal seeks to evaluate antibiotic prescribing in homebound older adults using a national cohort of homebound Veterans. Veterans who are homebound may receive home-based primary care (HBPC), which is comprehensive primary care delivered in the Veteran’s residential home by an interdisciplinary team of providers. Alternatively, homebound Veterans may receive office-based primary care (OBPC). The candidate envisions a pilot study involving peer-to-peer comparisons of antibiotic prescribing across regional HBPC programs. This proposal will address key knowledge gaps that stand in the way of such a pilot study. Because little is known about antibiotic prescribing in homebound Veterans, Aim 1 will compare the prevalence of antibiotic prescriptions in Veterans who used HBPC with those who used OBPC. Aim 2 will take up the broader challenge of assessing adherence to standards of care indicating that a urinalysis should be collected during treatment of urinary tract infection. Among homebound Veterans with suspected urinary tract infection treated with an antibiotic, Aim 2 will compare the proportion of Veterans having an order for a urinalysis between those who used HBPC and those who used OBPC. The candidate, Dr. Datta, is an infectious diseases physician at the Yale School of Medicine and Assistant Hospital Epidemiologist at the Veterans Affairs Connecticut Healthcare System (VACHS). He has an active role on the VACHS Antimicrobial Stewardship Program and a track record of early success, including several high-impact original reports, professional awards, and support from Yale Pepper Center and NIH. His primary co-mentors, Dr. Manisha Juthani-Mehta and Dr. Terri Fried, are internationally-recognized authorities on urinary tract infections and medical decision-making, respectively, in older adults. He has recruited another mentor, Dr. Andrew Cohen, with expertise in HBPC. This mentorship team will contribute complementary perspectives and expertise both to the proposed research and to the career development plan. Dr. Datta has outlined a rigorous program of training that draws upon resources from Yale University and the Department of Veterans Affairs that focus on data use and information systems for quality improvement programs. Execution of the proposal will facilitate Dr. Datta’s emergence as an independent investigator at the forefront of geriatric infectious diseases, antibiotic stewardship, and infection prevention.
 
9. Project Title: Caregivers of Parents with ADRD: The Relation of Recalled Experiences to Personal Health Preferences and Perceived Caregiving Efficacy: small REC (2021-2022)
  Leader: Emily Mroz
  Over 11 million adults currently provide unpaid, family care to close others with ADRD. Informal caregiving is an “essential feature of health care provision” in the US and worldwide (Schulz, 2013). Providing care for loved ones with Alzheimer’s Disease and Related Dementias (ADRD) is one of the most common, intensive, and challenging forms of informal caregiving (Basu et al., 2021; Connors et al., 2020). Caregivers for this population, often middle-aged adult children (Kasper et al., 2015), are vicariously exposed to negative consequences of aging (e.g., memory and autonomy loss, deterioration of sense of self, frailty; Dubljevic, 2020), influencing their expectations for their own transition to older adulthood and potential for developing health issues. Informal caregivers of persons living with ADRD consistently report a strong motivation to make meaning of their caregiving experiences, including identifying lessons learned (e.g., Cherry et al., 2019). The proposed study will establish themes of relations between recalled experiences from informal caregiving for a parent with ADRD, a) personal health preferences and behaviors, and b) perceived caregiving efficacy.
 
10. Project Title: Improving Hospital-Level Mortality Performance for Major Surgery in Older Adults: A Mixed Methods Study: small REC (2021-2022)
  Leader: Robert Becher
  Despite decades of efforts to improve care for patients undergoing major surgery, there remains substantial variation across hospitals in surgical mortality. For adult patients undergoing common general surgery operations, standardized mortality ratios range from an average of 1.7 at poor-performing hospitals to a mean of 0.5 at high-performing hospitals, more than a three-fold difference. For older persons, deficient surgical care is especially problematic. Major surgery is a common event in the lives of community-living older persons, with a 5-year cumulative incidence of 13.8%, representing nearly 5 million persons aged 65 years or older in the US. This value will increase substantially in the coming years based on the projected doubling of this age group to 98 million people by the year 2060. Therefore, despite the importance of major surgery as a defining health issue for older persons, we know little about what distinguishes poor-performing from exceptionalperforming outlier hospitals with high- versus low-mortality. This lack of evidence about what accounts for hospital mortality variation for geriatric surgery is a critical gap in our current knowledge. To facilitate improvements and achieve truly optimal perioperative outcomes for older persons undergoing major surgery, quality improvement science espouses the concept that we must first accurately define the landscape of the quality problem. One novel approach to examining the variation in healthcare quality is called positive deviance. This mixed methods analytic strategy postulates that hospital structures, processes, and internal environments may influence clinical outcomes. While the positive deviance approach has proven instrumental in improving hospital-level quality for other fields of medicine, it has not previously been applied to surgery. Grounded in the tenets of positive deviance, we will employ both quantitative and qualitative research in a complementary fashion to: (1) evaluate hospital-level mortality performance for older persons undergoing major surgery; (2) compare the patient-, operation-, and hospital-level characteristics between the highmortality and low-mortality hospitals for older persons undergoing major surgery; and (3) develop the methods and processes necessary for a full-scale qualitative evaluation of the hospital-specific efforts that may explain hospital-level mortality performance at the high-mortality and low-mortality hospitals for older persons undergoing major surgery. By taking a mixed methods approach, the proposed Pepper Scholar project will provide information that is essential to understanding the hospital-level sources of variation in mortality for geriatric surgery. These results, coupled with a robust career development plan and experienced mentoring, are expected to lay the groundwork for a subsequent novel and innovative large-scale, mixed methods R01 grant, fully utilizing the positive deviance approach on a national level, to define, test, disseminate, and implement evidence-based, hospital-level efforts to elevate hospital performance for older persons having major surgery in the US.
 
DEVELOPMENT PROJECTS (4 Development Projects Listed)
1. Project Title: Yale Study Support Suite (YES3): Exporter (2021-2022)
  Leader: Katy Araujo
  Core(s):
  The YES3 Exporter provides substantial enhancements over the standard REDCap export which allows downloading in either vertical or horizontal format, faster download times, customized data dictionary, and a crosswalk file for external reporting. This latter feature will be incorporated as a beta feature (pending additional funding to expand and refine) and was inspired by our involvement with NIA-CROMS reporting requirements using Advanced Programming Interfaces (APIs) to report enrollment data to NIH.
 
2. Project Title: Yale Study Support Suite (YES3): Data Visualization (2021-2022)
  Leader: Brent Vander Wyk
  Core(s):
  Dr. Vander Wyk is collaborating on a joint development project between the BC and the Operations Core (OC) called the Yale Study Support Suite (YES3): Data Visualization. The goal is to partially automate the time-consuming process of generating consort diagrams and descriptive tables for submission of original reports to scientific journals.
 
3. Project Title: COVID-19 in Older Adults: A Longitudinal Assessment (VALIANT): (2020-2022)
  Leader: Andrew Cohen, Lauren Ferrante, Alexandra Hajduk
  Core(s):
  The objective of this longitudinal study is to learn about the long-term effects of COVID-19 on the health outcomes that matter most to older adults, including physical function, cognition, and freedom from burdensome symptoms.
 
4. Project Title: NOSI YES3 Software (2021-2023)
  Leader: Cynthia Brandt
  Core(s):
  This year, we secured a supplemental NOSI grant funded by the Office of Data Science Strategy (ODSS). With the award, we are refactoring and refining high-utility software that has been used to support our most successful studies including DCare, STRIDE, SILVER-AMI, and VALIANT. The NOSI award consists of a Web Portal EM and Dashboard EM. The YES3 Web Portal EM provides researchers with an intranet platform to deliver customized group communications, study documents, announcements, and real-time performance reports. The YES3 Dashboard EM (see Diagram 1) provides a feature-rich control panel used to manage workflow; view, filter, and manage participant status; track visit windows; communicate with study staff, and monitor outcomes. The YES3 Dashboard provides the research team with an organized, real-time view into study activities and the necessary tools to manage the study protocol effectively. In turn, this can position the study to on-time data collection metrics and study milestones, improved data quality, and more efficient staff management. The code can be modified and repurposed by any REDCap software developer to allow future innovation. We will disseminate these EMs through the REDCap EM Repository and plan to feature our work within the National OAIC network and NIA Research Centers Collaborative Network (RCCN).
 
RESEARCH (22 Projects Listed)
1. Project Title: Assessment of a Novel Emergency Care Equity-Based Caregiver Outcome Measure
  Leader(s): GETTEL, CAMERON
    YALE UNIVERSITY
    ALZHEIMERS ASSOCIATION ARCOM-22-878456 / ( 2021 - 2023 )
  Core(s):
  Dr. Cameron Gettel and colleagues will conduct a study to develop and validate the novel Caregiver-reported Outcome Measure for Emergency Care Transitions (COMET) tool and assess it across diverse racial, ethnic, and socioeconomic status populations. This novel measure will identify care transition outcomes that are meaningful to caregivers of people with dementia. The researchers will conduct interviews with older individuals and their caregivers recruited from emergency departments in New Haven, CT, to inform the development of the COMET tool. Then, they will test its feasibility and validity among caregivers of people with dementia who were recently discharged from an emergency department. Finally, the team will investigate the association between COMET tool scores and rates of emergency department return visits for people with dementia.
 
2. Project Title: CIRCADIAN RHYTHM AS A NOVEL THERAPEUTIC TARGET IN THE INTENSIVE CARE UNIT
  Leader(s): KNAUERT, MELISSA P
    YALE UNIVERSITY
    NIH K23HL138229 / ( 2018 - 2022 )
  Core(s):
  PROJECT SUMMARY Candidate: My long-term career goal is to be an independent patient-oriented researcher who will improveoutcomes in the intensive care unit (ICU) by investigating questions and developing interventions at theintersection of sleep physiology, circadian biology, and critical illness. I have proposed career developmentactivities that will prepare me to successfully conduct a series of investigations focused on understanding ICUcircadian rhythm abnormalities and the associated effects on ICU sleep disruption, delirium, and broadercritical illness outcomes. I have relevant clinical training in critical care and sleep medicine. I have gained initialpatient-oriented research experience by conducting several studies related to sleep disruption in the ICU. Inthis K23 application, I am proposing specific training in circadian biology with a focus on (1) circadian rhythmmeasurement, (2) circadian entrainment interventions, and (3) longitudinal data analysis. Completion of thesetraining activities will bridge current knowledge gaps and set up future success as an independent investigator. Mentors and Environment: I will be mentored by Drs. Henry Klar Yaggi, Margaret Pisani, and NancyRedeker, a team of experienced, committed experts in the fields of sleep medicine, critical care medicine,circadian measurement, ICU delirium, and patient-oriented research. This team has demonstratedcollaborative success, and each member brings unique expertise. I will also work with advisors Dr. KennethWright (circadian biology expert) and Dr. Terrence Murphy (analytics expert). My department Chairperson (Dr.Gary Desir) and Section Chief (Dr. Naftali Kaminski) have provided assurance that I will dedicate at least 75%of my time to career development activities. We will recruit study subjects from the Yale-New Haven HospitalMedical ICU which is a high volume ICU with sufficient patients to make this project feasible. Our section'sTranslational Research Core and Medical ICU Biorepository will support this project. Mentored Research Project: Delirium affects 50-80% of medical ICU patients. Prevention and treatmentstrategies are limited, and delirium is associated with poor outcomes including increased mortality. BecauseICU sleep disruption is likely to be a contributor to the development of ICU delirium, sleep promotion isrecommended for delirium treatment and prevention. Currently, there is a lack of investigation regarding thepotentially significant contribution of circadian abnormalities to the problem of ICU sleep disruption andconsequent delirium. Circadian abnormalities are potentially modifiable, and thus constitute a novel therapeutictarget for ICU delirium. This project will prospectively study ICU patients (N=100) with detailed circadianmeasures. We will examine the impact of ICU light levels on circadian abnormalities and examine theassociation between circadian abnormalities and days of delirium. In addition, we will conduct a pilotrandomized controlled trial (N=50) to assess the feasibility of providing daytime bright light to ICU patients topromote circadian entrainment.
 
3. Project Title: THE PREDICT STUDY (PRE-ICU DETERMINANTS OF POST-ICU FUNCTIONAL OUTCOMES AMONG OLDER ADULTS)
  Leader(s): FERRANTE, LAUREN
    YALE UNIVERSITY
    NIH K76AG057023 / ( 2017 - 2022 )
  Core(s):
  PROJECT SUMMARY/ABSTRACTCandidate: My career goal is to become an independent physician-scientist and national leader in geriatriccritical care outcomes research whose body of work improves the long-term functional outcomes of critically illolder adults. My clinical training as a Pulmonary & Critical Care Medicine (PCCM) physician and researchtraining in Geriatric Clinical Epidemiology have prepared me to pursue this career path. My track record ofearly success is evidenced by the publication of high-impact original reports and the receipt of 3 grants,including a GEMSSTAR award. I have already distinguished myself as a national leader in my specialty as wellas in geriatrics: I founded and am co-chair of the American Thoracic Society Critical Care Assembly's Agingand Geriatrics Working Group, and was recently selected as an incoming co-chair of the American GeriatricsSociety (AGS) Medical Subspecialties Section. My research efforts have been recognized nationally, with theAGS New Investigator Award, and at Yale, with the prestigious Iva Dostanic Physician-Scientist Award.Mentors and Environment: I have an exceptional team of mentors and advisors, including my primary mentorDr. Thomas Gill (Geriatrics), a leading expert on the epidemiology and prevention of disability, co-mentor Dr.Margaret Pisani (PCCM), an expert in critical care outcomes research, and advisor Dr. Terrence Murphy, abiostatistician with expertise in longitudinal studies of aging and critical care outcomes research. My researchand career development plans draw on the wealth of resources available at Yale, including the Yale Programon Aging/Claude D. Pepper Older Americans Independence Center, the Yale School of Public Health, and oneof the largest intensive care units (ICUs) in the country at Yale-New Haven Hospital. These resources, and thesupport provided by the Section of Pulmonary, Critical Care, and Sleep Medicine at the Yale School ofMedicine, provide an ideal environment for my career development and execution of the proposed research.Mentored Research Project: Nearly 1.4 million older adults survive an ICU stay each year, and many of thesewill suffer from increased disability. Our prior work has demonstrated that premorbid factors are stronglyassociated with the course of disability after a critical illness yet no mechanism exists to identify which olderICU patients are at risk of increased disability. To address this knowledge gap, I have proposed an innovativeresearch project that leverages the wealth of resources available at Yale in addition to two high-qualitylongitudinal datasets: the National Health and Aging Trends Study (NHATS) and Precipitating Events Project(PEP). The overall objective is to develop, externally validate, and pilot test a predictive tool (that incorporatespremorbid risk factors) to identify older ICU patients at risk of worsening post-ICU disability and provide apersonal estimate of the increase in disability. The results will inform the design and conduct of a largerprospective cohort study to test the accuracy of the tool in predicting post-ICU disability as well as asubsequent clinical trial testing interventions to improve post-ICU functional outcomes among older adults.
 
4. Project Title: DEMENTIA AND DECISION-MAKING FOR OLDER ADULTS WITHOUT SURROGATES
  Leader(s): COHEN, ANDREW B
    YALE UNIVERSITY
    NIH K76AG059987 / ( 2018 - 2023 )
  Core(s):
  PROJECT SUMMARY / ABSTRACTA growing number of older adults with dementia are unbefriended : they have impaired capacity and no familyor friends to make decisions on their behalf. Because such persons must be represented by a stranger most often a guardian, selected by the court they may receive care that is discordant with their preferences.Work by the candidate, for example, suggests that individuals with dementia who are under guardianship aremuch more likely to receive aggressive end-of-life treatment than those with family members available to makedecisions. Given the substantial difficulties involved in making decisions for a person with dementia whosevalues and priorities are unknown, the current application seeks to lay the groundwork for an innovative upstream approach among persons who still have capacity but do not have a potential surrogate, so that theyare at risk for becoming unbefriended. The candidate envisions an intervention whereby such persons wouldbe identified ahead of time and health professionals would elucidate their values and priorities. The proposedwork will address the key knowledge gaps that stand in the way of such an intervention. Because little isknown about the population that would be targeted, Aim 1 will use a unique national dataset to describe theprevalence and risk factors associated with older adults who are unable to name a surrogate. Aims 2 and 3take up the broader challenge of generating an advance care planning model tailored to the unique challengesof dementia. Aim 2 will involve using qualitative methods to ascertain the core information that shapestreatment decisions when an ideal surrogate is exercising substituted judgment. Aim 3 involves thedevelopment and validation of a tool, capturing this information, that can be used in clinical practice.The candidate, Dr. Cohen, is a geriatrician at the Yale School of Medicine with a track record of early success,including several high-impact original reports and a GEMSSTAR award from the NIA. He has engaged anexceptional mentorship team. His primary mentor, Dr. Terri Fried, is an internationally-recognized authority ondecision-making for older adults with serious illness. He has recruited three co-mentors and an advisor whosediverse academic backgrounds will contribute a remarkable richness of perspectives and expertise both to theproposed research and to the career development plan. Dr. Cohen has outlined a rigorous program of trainingthat draws upon resources from across Yale University as well as national training opportunities in mixedmethods research and leadership development. The extraordinary resources available from the Yale Sectionof Geriatrics and Program on Aging provide an ideal environment for the execution of the proposed researchand for Dr. Cohen s emergence as an independent investigator at the forefront of geriatrics, medical decision-making, and ethics.
 
5. Project Title: NLRP3 Inflammasome Activation and Mitochondrial Function in the setting of Aging and HIV Infection
  Leader(s): ZAPATA, HEIDI J
    YALE UNIVERSITY
    NIH K76AG064548 / ( 2019 - 2024 )
  Core(s):
  Project Summary/Abstract: Both the aging and the aging HIV-infected population are characterized by increased rates of metabolic syndrome (defined by abdominal obesity, dyslipidemia, insulin resistance and hypertension). Notably, metabolic syndrome is associated with the dysregulated, age-associated pro-inflammatory environment termed Inflamm-aging characterized by elevated levels of cytokines, acute phase reactants, and clotting factors. Chronic stimulation of innate immune receptors by both pathogen-associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs) is thought to contribute to age-associated chronic inflammation, but the mechanisms underlying the pathogenesis of metabolic syndrome in the context of aging and HIV disease remain an incompletely understood knowledge gap in the field. The NLRP3 (NOD- like receptor pyrin domain-containing 3) inflammasome is an intracellular protein complex, that is part of the innate immune response and mediates the caspase-1-dependent cleavage of pro-IL-1b and pro-IL-18 to their activated forms. While the NLRP3 inflammasome is activated by PAMPs, there is increasing evidence for a role of NLRP3 as a sensor of host metabolism via DAMPs, as shown by NLRP3 activation by a wide range of metabolites. Moreover, NLRP3 inflammasome activation is dependent on mitochondrial function. The NLRP3 inflammasome has been linked to the development of insulin resistance and other metabolic syndromes in mouse models, and has been minimally explored in both older adults and HIV-infected adults. The purpose of this proposal is to determine the effects of age and HIV infection on the NLRP3 inflammasome, and its relationship with mitochondrial function by comparing the following groups of subjects, young adults (21-35), and older adults (= 60 yrs) with and without HIV-infection. Aim 1 seeks to characterize the NLRP3 inflammasome and its relationship with mitochondrial function, in myeloid cells from peripheral blood and adipose tissue. Aim 2 seeks to characterize the metabolic pathways that are induced with activation of the NLRP3 inflammasome through RNA sequencing and CyTOF in myeloid cells from peripheral blood and adipose tissue. Data from both aims will be collected in conjunction with clinical characteristics including the components of metabolic syndrome. Our hypothesis is that increased age and HIV infection will result in dysregulated NLRP3 inflammasome function at baseline and with activation that is linked to mitochondrial dysfunction ultimately contributing to the development of metabolic syndrome in older and HIV-infected adults. The candidate, Dr. Zapata is an Infectious Disease physician at the Yale school of medicine, who has put together an interdisciplinary mentorship committee with expertise in immunology, aging, and metabolism. This training proposal is coupled with a career development plan that includes mentorship and didactic training in Immuno-metabolism, with an additional focus on learning the analysis of sequencing data, thus providing the tools that will allow the PI to apply for an R01 award.
 
6. Project Title: Evaluating Sleep Deficiency in Aging Populations
  Leader(s): MINER, BRIENNE
    YALE UNIVERSITY
    NIH K76AG074905 / ( 2021 - 2026 )
  Core(s):
  PROJECT SUMMARY/ABSTRACT Candidate: My career goal is to become an independent clinician-investigator focused on improving sleep- wake disturbances and preventing their adverse outcomes in older persons. My clinical training as a Geriatrics and Sleep Medicine physician and research training in Geriatric Clinical Epidemiology form the foundation on which I will build to reach this goal. My track record of success is evidenced by the publication of high-impact original reports and the receipt of 3 grants. I have distinguished myself as a national leader and received awards for my research from the Sleep Research Society, the American Academy of Sleep Medicine (AASM), and the American Geriatrics Society (AGS), including the AGS New Investigator Award and a career development award from the AASM Foundation. Mentors and Environment: I have an outstanding team of mentors and advisors, including my primary mentor, Dr. Thomas Gill (Geriatrics), an internationally recognized thought leader in aging research, and co- mentor Dr. Klar Yaggi (Sleep Medicine), an expert in conducting epidemiologic studies aimed at understanding the health outcomes of sleep disorders. I also have a team of advisors, selected based on their expertise in aging, sleep, qualitative and mixed-methods research, circadian biology and analysis, and instrument development. I have outlined a rigorous program of training that draws upon the wealth of resources across Yale University, including the Program on Aging/Claude D. Pepper Older Americans Independence Center, as well as national training opportunities in mixed methods research and leadership development. These resources, and the support of the Sections of Geriatrics and Sleep Medicine at the Yale School of Medicine, provide an ideal environment for my career development and execution of the proposed research. Mentored Research Project: Sleep-wake disturbances are associated with important adverse outcomes in older persons, including cognitive and functional decline. Our prior work has demonstrated that these disturbances are under-diagnosed in older persons, which may be due to the poor sensitivity of existing sleep questionnaires, the frequent co-occurrence of multiple sleep-wake disturbances, and the burdensome nature of objective sleep testing. We propose to develop and test age-appropriate, comprehensive subjective and objective sleep assessment tools to facilitate identification of older persons with sleep-wake disturbances. To accomplish this, we will assess sleep-wake disturbances using a broader construct termed, sleep deficiency , which is a condition causing functional impairment as a result of a deficit in sleep quality, sleep duration, and/or sleep that is out-of-sync with the body's natural clock (i.e., non-circadian sleep). The overall objective is to develop and pilot test tools to identify sleep deficiency in older persons. Future work will validate these tools, which can be used to target interventions to improve sleep health and prevent adverse outcomes.
 
7. Project Title: THE IMPACT OF AGING AND HIV INFECTION ON IMMUNOLOGIC AND TRANSCRIPTOMIC SIGNATURES OF INFLUENZA VACCINE RESPONSE
  Leader(s): SHAW, ALBERT C; KANG, INSOO ;
    YALE UNIVERSITY
    NIH R01AG055362 / ( 2017 - 2022 )
  Core(s):
  It is estimated that approximately half of HIV-infected individuals in the United States are over 50 years of age.Aging of the HIV-infected population has linked alterations in immune responses associated with age and theimmunologic consequences of chronic HIV infection. This intersection of HIV and aging will influence hostdefense against infection and response to vaccines. As a result, understanding the nexus of HIV-associatedimmune activation and immunosenescence takes on particular urgency. We will leverage insights from ourpublished and ongoing studies on the effects of aging on dysregulated innate immune pattern recognitionreceptor (PRR) function, a novel population of pro-inflammatory IL-7 receptor alow effector memory (EM) CD8 Tcells that are expanded in HIV-negative older adults, and on expansion of EM CD8 T cells in older HIV-positiveadults. We have also elucidated gene expression and immunologic signatures of influenza vaccine responsein young and older HIV-negative adults. These findings position us to illuminate the effects of aging and HIVinfection on innate and adaptive immune function, particularly following influenza vaccination. To addressthese questions, we have assembled an interdisciplinary group of investigators with expertise in the study ofaging of the innate and adaptive human immune systems, and in HIV immunology, biology and clinical care.Our overarching hypothesis is that the pro-inflammatory environment associated with age and with suppressedHIV infection potentiates immunosenescence in older adults with HIV disease. To test this hypothesis, we willenroll young (age 21-35) and older (age over 65) adults with HIV infection receiving high-dose influenzavaccine. We will employ state of the art methods including multichannel mass cytometry on whole blood toassess development and activation of major populations (e.g. monocytes, dendritic cells, NK cells,lymphocytes, neutrophils), including novel studies of platelets pre- and post-vaccine. We will evaluate innateimmune PRR function (including Toll-like and NOD-like receptor family members), where we previously foundage-associated alterations in cytokine production and costimulatory protein expression that were related toinfluenza vaccine response. We will also study T cell responses to in vitro vaccine antigen stimulation,including the IL-7 receptor alow EM CD8 T cell subset. Statistical modeling will include clinical and functionalcovariates (e.g. CD4+ T cell count, estimated duration of HIV disease and of ART, medical co-morbidities,medication use, functional status). Finally, we will derive gene expression signatures of influenza vaccineresponse in young and older adults with HIV disease, and compare these to those we previously identified inHIV-negative adults. We will employ state of the art analytic methods to integrate gene expression andimmunologic data to obtain a comprehensive view of the human immune response in the context of age andimmune suppression. These studies ultimately are aimed at identifying pathways amenable to pharmacologictargeting to improve immune and vaccine responses in older (and young) adults with HIV disease.
 
8. Project Title: ATTACHMENT BEHAVIORS IN PARENT CHILD DYADS COPING WITH EARLY STAGE ALZHEIMER'S DISEASE AND RELATED DEMENTIAS
  Leader(s): MONIN, JOAN E
    YALE UNIVERSITY
    NIH R01AG058565 / ( 2019 - 2023 )
  Core(s):
  Roughly 4 million adult children provide unpaid care to their parents with Alzheimer's disease and relateddementias (ADRD). Caring for a parent with ADRD can be stressful and negatively impact caregivers' health.While research on spousal caregiving dyads shows that emotionally supportive communication betweenspouses in the early stages of ADRD can protect caregivers' health, little is known about such interpersonalprocesses in parent-child dyads. This needs to be addressed because adult child caregivers and their parentsface different interpersonal challenges (e.g., navigating a reversal of the parent-child role) than spousal dyads.We have shown in our spousal caregiving work that mutual emotional support behaviors, defined as caregiversand care-recipients providing and receiving communication of safety, feeling comfortable expressingvulnerability and empathy, and giving and receiving tangible aid, decrease caregiving burden and protectpsychological health. Mutual emotional support behaviors are amenable to change, making them appropriatetargets for interventions. Our research is informed by attachment theory, which stipulates that the need foremotional security is a fundamental need in the parent-child dyad across the lifespan, especially in times ofcrisis. Our overarching hypothesis is that mutual emotional support behaviors can protect the health of adultchild caregivers and parents by reducing caregiver stress and negative coping strategies. We integrate ourhypotheses about mutual support into an existing dyadic caregiving stress model that shows how caregiverand care-recipient characteristics, primary and secondary stressors, caregiver appraisals and coping allinfluence both dyad members' health and relational functioning. To test our innovative model, we propose aStage 0 dyadic, longitudinal, and observational study of 200 dyads: older adults aged 60 and older with earlystage ADRD and one primary adult child caregiver. Both dyad members will be interviewed, using valid andreliable self-report measures, and have videotaped discussions about dementia-related stressors at baselineand a one-year follow-up. Mutual emotional support behaviors will be measured with an observational codingsystem created by Co-I Feeney, and blood pressure will be monitored. Dyadic analysis will be performed withmixed models and structural equation modeling. Aim 1 will examine whether mutual emotional supportbehaviors are associated with lower caregiver demand appraisals, caregiver perceived stress, and caregivernegative coping longitudinally. Aim 2 will examine whether mutual emotional support behaviors protect bothdyad members' health and relational functioning longitudinally and whether this is mediated by lower caregiverdemand appraisals, caregiver perceived stress, and caregiver negative coping. Aim 3 will examine mutualemotional support behavior differences by sex as a biological variable and contextual factors (e.g., SES,caregiver depression, relationship history). This will lead to a Stage 1 application to create an attachment-based intervention tool to protect the health of parents with ADRD and their adult child primary caregivers.
 
9. Project Title: FEASIBILITY OF VIRTUAL COACHING IN MAKING INFORMED CHOICES ON ELDER MISTREATMENT SELF-DISCLOSURE (VOICES)
  Leader(s): ABUJARAD, FUAD
    YALE UNIVERSITY
    NIH R01AG060084 / ( 2018 - 2022 )
  Core(s):
  7. PROJECT SUMMARYElder mistreatment (EM) is a major public health problem with prevalence estimate ranges from 7.6% to 12.7%among older adults. EM causes serious adverse outcomes for its victims including injury, increased serviceutilization, mental distress and increased mortality. A major barrier in EM is the inability toaccurately identify EM victims. It is estimated that only 1 in 24 cases become known to authorities. This isproblematic as older adults are not likely to report that they are being mistreated. To improve the screening forEM and promote self-disclosure we will study the Feasibility of Virtual cOaching in making Informed Choicesovercomingon Elder Mistreatment Self-Disclosure (VOICES). The overarching aim of this project is to VOICES that runson tablets and used by older adults screen for EM. VOICES will be utilizing virtual coaching, interactivemultimedia libraries (e.g. graphics, video clips, animations, etc.), techniques form electronic screening forintimate partner violence, and brief motivational interviewing designed to enhance identifying EM among olderadults. This project includes developing new screening framework, as well as a study to examine the feasibilityof this complex interventions in real-world settings. Our aims are: 1) to develop and refine the interactiveVOICES tool, which will promote self-identification and self-disclosure to increase reporting of EM at point-of-care in the ED setting. 2) to conduct a feasibility study (N= 800) examining the use of VOICES in a busy ED,and 3) to perform a preliminary evaluation of the accuracy of VOICES as a screening tool in correctlyclassifying EM cases that were referred to Adult Protective Services (APS).
 
10. Project Title: PRAGMATIC TRIAL OF THE EFFECTIVENESS AND COST-EFFECTIVENESS OF DEMENTIA CARE
  Leader(s): REUBEN, DAVID B.
    UNIVERSITY OF CALIFORNIA LOS ANGELES
    NIH R01AG061078 / ( 2018 - 2023 )
  Core(s):
  PROJECT SUMMARYIn the United States, an estimated 5.5 million persons are affected by Alzheimer's disease, the most commontype of dementia. The clinical manifestations of dementia are devastating and often lead to caregiver stress,burnout, and medical illnesses. Dementia is a prototype of a disorder with complex needs that span both thepatient and caregiver, medical and social domains, and health system and community-based organizations.In response, several dementia care programs have been developed to more comprehensively meet the needsof patients and their caregivers, including those based within health care systems and those based in thecommunity. These programs have been implemented at either single sites or on a relatively small scale; nonehas been replicated widely because of unanswered questions about effectiveness and cost-effectiveness.In November 2017, the Patient Centered Outcomes Research Institute (PCORI) approved a 4-site pragmaticclinical trial to compare the effectiveness of health-systems-based care (based on the UCLA Alzheimer's andDementia Care program) with community-based care (based on the Benjamin Rose Institute Care Consultationprogram) on patient- and caregiver-reported outcome measures, including behavioral symptoms and caregiverdistress (co-primary outcomes), and secondary outcomes of caregiver strain, unmet needs, and depressionover 18-months. Because of PCORI's mandate, neither intervention will be compared to usual care (thus, onlyrelative effectiveness can be determined). Nor will cost-effectiveness of either intervention be evaluated.The proposed research will add a third usual care (UC) arm and expand outcomes to include costs and healthcare utilization. This expansion will permit comparison of each of the intervention arms to current usual care,thereby providing multisite pragmatic randomized clinical trial evidence for effectiveness of the two activetreatment arms. It will also allow evaluation of whether paying for such care will offset the costs anddetermination of which intervention is more cost effective. The study will also conduct exploratory analyses oftertiary outcomes of both interventions versus usual care including mortality, time spent at home, long-termnursing home placement, physician and patient/caregiver satisfaction and comparing all three groups onseveral types of utilization and out-of-pocket expenses.The study's questions are fundamental to planning for the clinical care of persons with dementia. Theyaddress both clinical effectiveness and cost-effectiveness. By answering these questions, clinicians, healthsystems, and insurers can make decisions about which programs to promote, scale and disseminate.
 
11. Project Title: REHABILITATION AT HOME USING MOBILE HEALTH IN OLDER ADULTS AFTER HOSPITALIZATION FOR ISCHEMIC HEART DISEASE (RESILIENT)
  Leader(s): DODSON, JOHN A
    NEW YORK UNIVERSITY SCHOOL OF MEDICINE
    NIH R01AG062520 / ( 2019 - 2024 )
  Core(s):
  Project SummaryParticipation in ambulatory cardiac rehabilitation (CR) by patients with ischemic heart disease (IHD) remainslow. By recent estimates, fewer than two thirds of eligible patients are referred, and fewer than half of thosereferred participate. Even among those referred, multiple barriers to participation include limited facilities,competing time demands, high out-of-pocket costs, and prolonged wait time. Barriers to CR are particularlyhigh in older adults (age =70), due to factors such as physical impairments or transportation barriers, althoughthese patients may simultaneously have the greatest potential to benefit. Mobile health-enabled CR (mHealth-CR) for IHD which involves delivery of CR via portable electronic devices has the potential to increaseengagement by reducing participation barriers, but it remains largely untested outside of small studies inrelatively healthy young persons. It is therefore unclear what proportion of older adults with IHD and barriers totraditional CR are able to engage with mHealth-CR, and whether mHealth-CR leads to better outcomes thanusual care. Therefore, we propose RESILIENT: Rehabilitation at home using mobile health in older adultsafter hospitalization for ischemic heart disease. This is a prospective, multicenter, non-blinded randomizedclinical trial (with blinded assessment of primary endpoint) to evaluate engagement and outcomes withmHealth-CR among older adults with IHD, identified at the time of acute myocardial infarction (AMI),percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG). The trial will be conductedat two academic medical centers: NYU School of Medicine and Yale School of Medicine, which collectivelyserve a diverse patient population and have a track record of successfully recruiting older adults in clinicalresearch studies. We will randomize 400 older adults with IHD to receive mHealth-CR (n=300) or usual care(n=100) for 3 months. Our intervention combines mHealth-CR software, delivered via a tablet device, withbaseline counseling and weekly phone calls by an exercise therapist over 3 months. Intervention and usualcare groups will also receive a standard referral to ambulatory CR in accordance with guidelines, as well asdynamic assessment of activities of daily living (ADLs). The primary efficacy endpoint is change in functionalcapacity, assessed by 6 minute walk distance. Secondary efficacy endpoints are goal attainment, healthstatus, ADLs, hospital readmission, and death. The engagement endpoint is defined by weekly completion ofmHealth-CR tasks. We hypothesize that mHealth-CR will improve a range of outcomes, and that distinctpatterns of engagement will be discerned. The PI for this project (Dr. Dodson) is an Early Stage Investigatorwith a focus on cardiovascular outcomes research among older adults; additional investigators have a widerange of expertise in geriatrics, biostatistics, behavioral science, cardiac rehabilitation, and computer science.The study results could lead to new sustainable and resource-efficient CR strategies among older adults withIHD, and lay the groundwork for a subsequent large multi-center clinical trial.
 
12. Project Title: Enhancing the Efficiency of Pragmatic Clinical Trials Using Administrative Data: Analysis of the STRIDE Study
  Leader(s): ESSERMAN, DENISE ; GANZ, DAVID ; LATHAM, NANCY K;
    YALE UNIVERSITY
    NIH R01AG071528 / ( 2022 - 2026 )
  Core(s):
  Project Summary & Abstract Pragmatic clinical trials aim to test interventions within typical healthcare settings to produce generalizable results. Successfully implementing pragmatic trials requires overcoming a number of challenges, including acquiring data as efficiently and non-intrusively as possible, so as to encourage maximum study participation at lowest cost. Administrative data are a potential solution for some pragmatic trials. These data derive from routine activities in the healthcare system, including clinical care (e.g., billing systems; use of electronic health records). With administrative data, participants can be passively followed over long time periods, potentially with decreased participant burden, decreased loss to follow-up from inability to contact a participant and decreased cost compared to alternatives (e.g., participant interview or review of medical records). All of these features could enhance both internal and external validity and reduce the overall cost of a trial. Limited empirical work exists on the comparative value of various data sources for ascertaining outcomes in pragmatic trials. We are in a unique position to the leverage the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial, a ten-site pragmatic, cluster-randomized trial focused on serious fall injury in community- dwelling older adults, to determine whether outcome ascertainment in pragmatic clinical trials could be simplified through automated data collection, without introducing significant imprecision or bias, thus reducing costs. STRIDE has multiple sources of data including multiple reference standards (adjudicated outcomes; self-reported outcomes) and two administrative data sources (fee-for-service Medicare data; administrative data from clinical trial sites). We will be able to couple currently available administrative data with newly available Medicare Advantage data to have a complete administrative picture of this almost universally Medicare eligible population. Complete data will give us the opportunity to achieve the overall goal of this research proposal, which is to develop a framework for determining whether administrative data can be used in pragmatic clinical trials in a Medicare eligible population to efficiently and accurately ascertain the primary outcome. To achieve this goal, our project has three aims: (1) develop and validate algorithms for detecting serious fall injuries from administrative data against the reference standards of STRIDE events; (2) determine the impact of the algorithms on trial findings; and (3) assess the cost efficiency (savings) of conducting the trial using administrative data.
 
13. Project Title: Circadian Rhythms and Innate Immune Response in Aging
  Leader(s): FIKRIG, EROL ; SHAW, ALBERT C;
    YALE UNIVERSITY
    NIH R01AI142624 / ( 2019 - 2024 )
  Core(s):
  Circadian rhythms play crucial roles in a wide range of physiologic and behavioral processes. In mammals, variations in light intensity and other environmental cues are integrated by a master pacemaker in the suprachiasmatic nuclei of the hypothalamus, which entrains multiple peripheral circadian clocks via neuroendocrine mechanisms. The clock at the molecular level consists of a network of transcription factors organized in a series of highly conserved transcription-translation feedback loops. While circadian rhythms in mammals are typically associated with sleep-wake, body temperature, cardiovascular, and metabolic regulation, circadian periodicity has also been reported for immunologic processes as well, including daily oscillation in levels of cell populations such as CD4 and CD8 T cells and cytokine expression. We were the first to report that Toll-like Receptor (TLR)-9, one of the pattern recognition receptors of the innate immune system, shows daily variation in expression and function that is modulated by circadian clock components in mice. We found that both response to a TLR9 adjuvanted vaccine and disease severity in a TLR9-dependent sepsis model were dependent on the timing of vaccination or sepsis induction, implicating circadian control as a novel mechanism of innate immune regulation. Our preliminary data also suggests circadian variation of TLR responses in humans as well. Several lines of evidence suggest that circadian rhythms are disrupted by aging in humans and mice, and knockout mice deficient in clock genes develop phenotypes associated with premature aging. However, there remains a knowledge gap as to whether aging influences circadian variation in TLR responses in mice and humans. We hypothesize that such variation will be attenuated by aging in both humans and mice, and have assembled in interdisciplinary group of investigators with expertise in human and mouse immunology, sleep research, chronobiology and aging research to test this hypothesis. We will focus on evaluating TLRs associated with response to viral infection (TLR3, 7, 9 in mice and TLR3, 7-9 in humans) for which our published and unpublished data in mice suggest circadian variation. We will assess circadian TLR gene expression in purified populations of B cells, monocytes, and dendritic cells, as well as in vivo and in vitro circadian variation in TLR-dependent cytokine production, costimulatory protein expression, and response to viral infection in young and aged (20-22 months of age) mice and young (21-30 years) and older (= 65 years) humans. The proposed human studies will integrate immunologic data with physiologic parameters of circadian cycling standard in chronobiology, such as polysomnography, and measurements of cortisol and core body temperature. The study of circadian innate immune function is likely to break new ground in considering temporal variation in susceptibility or outcomes of infection, or in response to treatment. These insights would have substantial impact in older adults, who are known to have increased morbidity and mortality from infectious diseases and impaired responses to vaccination.
 
14. Project Title: Effectiveness of Strategies to Improve Outcomes after Hospitalization for Acute Myocardial Infarction in Older Adults
  Leader(s): CHAUDHRY, SARWAT I
    YALE UNIVERSITY
    NIH R01HL160822 / ( 2022 - 2025 )
  Core(s):
  Acute myocardial infarction (AMI) is consistently ranked as one of the top five most expensive conditions billed to Medicare and has been the target of several cost containment measures, including Medicare s Hospital Readmissions Reduction Program. To improve outcomes after AMI hospitalizations, payers have implemented public reporting, financial penalties, and alternative payment models that incentivize the assumption of financial risk such as capitation. These measures have not been accompanied by evidence-based guidelines on how health systems can improve outcomes after hospitalization. An impediment to such guidance has been an incomplete understanding of patient-level factors that may influence the effectiveness of strategies to improve post-AMI hospitalization outcomes as applied in real-world settings. Notably, 30% of patients hospitalized for AMI are age = 75. These patients have lower physiologic reserve and more functional impairments, including those in cognition and physical capabilities, than younger patients. In the SILVER-AMI study, we enrolled 3041 patients age = 75 hospitalized for AMI at 94 hospitals. The primary objective was to evaluate the contribution of functional impairments and geriatric conditions to improving risk prediction for mortality within 6 months of hospital discharge. The premise of the SILVER-AMI study was that risk prediction at the time of discharge could identify high-risk patients who might benefit from more intensive post-hospital care. Findings from SILVER-AMI have demonstrated that functional impairments substantially improve risk prediction for important outcomes. We did not obtain Medicare data in this study so could not examine strategies being deployed in an effort to improve post-AMI outcomes. The overall objective of this proposal is to refine our understanding of the impacts of home health care (HHC) (Aim 1), early outpatient care (Aim 2), and Medicare Advantage (MA) (Aim 3) after AMI hospitalization by examining their effects in the context of functional impairments and illness severity. We will focus on outcomes of primary importance to older patients, including home days (days alive out of the hospital and other inpatient facilities) and health status, as well as disease-specific outcomes of relevance post-AMI. We will merge data from the SILVER-AMI study with Medicare data to achieve our aims. Combining these data sources will afford us the unique opportunity of accounting for an array of rigorously assessed covariates that are not generally available in studies using only administrative data and to identify patients who may benefit most from post-discharge services. In addition to accounting for a rich array of measured confounders, we will employ advanced statistical techniques to address bias from unmeasured confounding. We have assembled a team with a track record of collaboration and expertise in cardiovascular outcomes, home health care, outpatient care delivery, epidemiology, and biostatistics. This hypothesis-driven research will leverage the most comprehensive set of data on functional impairments and geriatric conditions collected during AMI hospitalization on a large, national cohort to inform strategies to improve outcomes of importance to older patients.
 
15. Project Title: A Multifactorial Approach to Evaluating Disparities in Outcomes after Major Surgery in Disadvantaged Older Persons
  Leader(s): GILL, THOMAS MICHAEL; BECHER, ROBERT DAVID;
    YALE UNIVERSITY
    NIH R01MD017298 / ( 2022 - 2026 )
  Core(s):
  Major surgery is a common event in the lives of community-living older persons, with a 5-year cumulative inci- dence of 13.8%, representing nearly 5 million persons aged 65 years or older in the US. This value will in- crease substantially in the coming years based on the projected doubling of this age group to 98 million by 2060. As our society ages, it is also becoming increasingly diverse, with growing proportions of racial/ethnic minorities and other disadvantaged groups. Yet, despite the public health imperative, disparities in outcomes after major surgery in disadvantaged older persons are poorly understood. Prior research has generally relied on large administrative datasets and, hence, has usually been restricted to disadvantaged populations defined only by individual-level demographic characteristics, a small number of short-term outcomes, and a limited set of explanatory variables. To address current gaps in knowledge, and build the evidence for action, a more ro- bust approach is needed that focuses on multiple disadvantaged populations of older persons, emphasizes the importance of social contextual factors in defining the scope and complexity of disadvantage, includes a larger array of geriatric-specific outcomes that are clinically meaningful, evaluates a comprehensive set of explana- tory variables that include modifiable patient-centered variables, and assesses the use of post-surgical pallia- tive treatments such as hospice. The overarching objective of this proposal is to identify and elucidate sources of potential disparities in outcomes after major surgery in disadvantaged older populations, defined on the ba- sis of individual-level and social contextual factors. Building on our prior work, we will use high-quality data from the National Health and Aging and Trends Study (NHATS), an ongoing nationally representative longitudi- nal study that includes 7,600+ community-living persons aged 65+ years with oversampling of Blacks, compre- hensive annual assessments with patient-centered phenotypic data that are not available in administrative da- tasets, cohort replenishment at 5-year intervals, and linkages to Medicare and geographic data. This unique resource will permit a series of innovative longitudinal analyses at the patient level that will complement sys- tems-based research on the quality of surgical care. We will rigorously test three distinct but related hypothe- ses: (1) disparities after major surgery in older persons will be observed consistently for multiple outcomes across multiple disadvantaged populations; (2) for each disadvantaged population, these disparities in out- comes will be largely attributable to a set of patient-centered variables, including several that are potentially modifiable; and (3) similar disparities will be observed in the use of hospice but will not be as easily explained. By taking a comprehensive, multifactorial, and multilevel approach that emphasizes the importance of social contextual factors, the proposed research will build the evidence that is essential to understanding the mecha- nisms of potential disparities in outcomes after major surgery. These actionable results will inform novel inter- ventions, collaborations, and policies designed to improve these outcomes in disadvantaged older persons.
 
16. Project Title: Evaluating Sleep Deficiency in Older Persons
  Leader(s): MINER, BRIENNE
    YALE UNIVERSITY
    NIH R03AG073991 / ( 2021 - 2023 )
  Core(s):
  PROJECT SUMMARY Sleep complaints occur in nearly half of older persons and are associated with cognitive decline, disability, and many other adverse outcomes. Accurate and feasible evaluation is needed to identify persons at risk for these adverse outcomes. However, the traditional approach to evaluating sleep complaints in older persons is limited for several reasons. First, because the underlying etiology is likely to be multifactorial in older persons, a comprehensive strategy that considers the multiple domains contributing to sleep complaints is needed. Second, reliance on self-report alone may miss severe sleep problems or specific sleep disorders in older persons. Third, polysomnography is the gold standard for evaluation of sleep apnea and sleep architecture (i.e., arousals from sleep and deeper, more restorative sleep stages), but it is costly, burdensome, and may not be feasible or reflect habitual sleep patterns. To address these limitations, we propose to evaluate sleep deficiency, a comprehensive construct aimed at identifying factors contributing to sleep complaints in three domains: 1) poor sleep quality, including sleep disorders; 2) insufficient sleep duration; and 3) non-circadian sleep (abnormalities of sleep timing, sleep regularity, and daytime alertness). Novel, home-based measures from sleep headbands and actigraphy will objectively evaluate sleep architecture and duration, detect sleep apnea, and assess non- circadian sleep. Measures of sleep quality, duration, and non-circadian sleep from the headbands and actigraphy can be performed over multiple nights in the home. They may be more feasible than laboratory- based measures and more reliable than self-reported measures. We will enroll 50 community dwelling persons 65 years with sleep complaints (insomnia or daytime sleepiness) to undergo evaluation of sleep deficiency using validated self-reported measures, single-night home-based polysomnography, 7 nights of the headband, and 7 days and nights of actigraphy. The aims of this study are to compare self-reported versus objective measures of sleep deficiency. We hypothesize that the headband measures will have stronger concordance with polysomnography than self-report and that concordance between self-reported and actigraphy measures of non-circadian sleep will be low. Collectively, such results would suggest the need for objective measures of sleep deficiency in older persons. The proposed work will develop robust objective measures of sleep deficiency that are feasible in this vulnerable and understudied population. These measures may advance the management of sleep deficiency in future work through enhanced identification of underlying sleep problems, improved targeting and monitoring of future interventions, and reduction of the risk of adverse health outcomes.
 
17. Project Title: Generating novel predictive models to estimate the risk of future ASCVD & Dementia in older adults
  Leader(s): NANNA, MICHAEL
    YALE UNIVERSITY
    NIH R03AG074067 / ( 2021 - 2023 )
  Core(s):
  Response to Grants for Early Medical/Surgical Specialists' Transition to Aging Research (GEMSSTAR) Competition Title: Generating novel predictive models to estimate the risk of future ASCVD & Dementia in older adults Project Summary/Abstract: A person s baseline risk determines to a large extent their anticipated benefit from many preventive treatments. Older patients desire to live longer while maintaining cognitive function and freedom from dementia, including Alzheimer s disease, the #1 cause of morbidity and disability in older adults. Older adults also prioritize avoiding atherosclerotic cardiovascular disease (ASCVD), the #1 killer of older adults. Importantly, many risk factors for Alzheimer s disease and dementia also increase risk for ASCVD. Alzheimer s disease is the most common etiologic basis for incident mild cognitive impairment and dementia in older adults and can be identified as the cause in 70-75% of cases. Thus, providing older patients with personalized risk estimates for both dementia, including Alzheimer s disease, and ASCVD could facilitate a comprehensive, evidence-based and patient-centered approach to therapeutic decision making in older adults. Unfortunately, current risk models were derived in younger adults, and fail to accurately predict risk in older adults. Second it remains unclear whether existing ASCVD risk models can also predict dementia risk and vice versa. Finally, to date, no one has evaluated whether these risk estimates help stratify therapeutic benefits of intervention in older adults. Leveraging a mentorship team of world experts in geriatrics, cardiology, and epidemiology, I will utilize data from subjects =75 years old from the National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts in order to develop a clinical risk model to estimate risk of dementia, including Alzheimer s disease, at 5 years from the selected baseline visit (Aim 1). In parallel, we will develop a clinical risk model to estimate the risk of ASCVD over the same time period in the same population of individuals =75 years old. In addition to traditional risk factors, we will derive these models using a novel set of candidate predictors not previously included in prior risk models including baseline cognition, functional status, depression, and mobility. Both models will then be externally validated using data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort (Aim 2). Finally, we will apply our model to patients =75 years old from the Systolic Blood Pressure Intervention Trial (SPRINT) in order to determine whether therapeutic benefit from intensive vs. conservative anti-hypertensive therapy in older adults differs across levels of predicted risk (Aim 3). Once developed and validated, we will develop an electronic health record-based version of the model for widespread dissemination and use in clinical care. The training I will receive through this work will give me expertise in model building and deployment and broaden my research interest in dementia including Alzheimer s disease. It will also lay the groundwork for a future application for the Paul B. Beeson Emerging Leaders Career Development Award and other independent funding, with the ultimate goal of becoming an independent clinician-researcher focused on the care of older adults.
 
18. Project Title: Linked Lives, Linked Health: Health Trajectories of Persons with Cognitive Impairment and Their Caregivers' Health
  Leader(s): ZANG, EMMA XIAOLU
    YALE UNIVERSITY
    NIH R21AG074238 / ( 2021 - 2023 )
  Core(s):
  Project Summary More than 20% of people =65 years old living in the US are cognitively impaired, with diagnoses ranging from mild cognitive impairment (MCI) to dementia. Because of its progressive nature, as persons with cognitive impairment (hereafter PCIs ) experience decline in cognitive function and other health outcomes, the health of their caregivers or care partners (CG) may also be negatively impacted due to factors such as increased caregiving burden and stress. Determining how the health trajectories of all PCIs affect CG health outcomes over the course of cognitive decline will build a scientific foundation to design effective policies to reduce caregiving cost and improve care quality. The proposed study will investigate the health trajectory patterns of PCIs and their relationships with CG health in the US. Data will be drawn from the annual National Health and Aging Trends Study in 2011 2019 coupled with data from the National Study of Caregiving in 2011, 2015, 2017, and potentially 2021 if available. We will consider general health status, physical health, and psychological well-being for both PCIs and CGs. Our unique contribution to the field of dementia research is threefold: 1) our proposed study is the first to examine both PCI and CG health using a trajectory approach; 2) we will use high-quality population data; 3) we will study the full spectrum of cognitive impairment, rather than only the most severe scenarios. We will first describe health trajectories among PCIs and examine how their trajectories predict CG health across time. For each health outcome, we will apply the single-trajectory Bayesian group-based trajectory model (BGBTM) to identify distinct trajectory groups for PCIs and apply linear regression models to predict CG health. We will also determine how PCI health trajectories are related to CG health trajectories. Applying the dual-trajectory BGBTM, we will visually demonstrate how PCI and CG health trajectories are parallel in time and estimate the probability of one trajectory pattern among CGs conditional upon one pattern among PCIs. Second, we will determine how the relationships examined above are moderated by caregiving and sociodemographic characteristics of CGs. We hypothesize that a distant relationship with PCIs, high-intensity caregiving, a heavy caregiving burden, and social disadvantage are associated with adverse health outcomes and trajectories among CGs, and that these characteristics moderate the association between PCI health trajectories and CG health outcomes and trajectories. Finally, we will determine joint trajectories in PCI cognition and other health outcomes, as well as the impact of PCI cognitive trajectories on CG health. Findings of this study will assist policymakers in understanding the health consequences of caregiving for PCIs, which will build a scientific foundation for the development of effective interventions to improve the quality of care and reduce long-term care cost. Further, understanding the prognosis for various types of PCI and CG health trajectories may enable better preparation of caregiving and ultimately higher quality care.
 
19. Project Title: Priorities Aligned Deprescribing for Persons Living with Dementia and their Caregivers
  Leader(s): STEINMAN, MICHAEL A.; BOYD, CYNTHIA MELINDA;
    NORTHERN CALIFORNIA INSTITUTE/RES/EDU
    NIH R24AG064025 / ( 2019 - 2024 )
  Core(s):
  Project Summary Title: Priorities Aligned Deprescribing for Persons Living with Dementia and their Caregivers Persons living with dementia (PlwD) have a significant burden from multiple chronic conditions and overmedication, and particularly benefit from deprescribing to reduce polypharmacy. Deprescribing is a systematic process to reduce medications with unacceptable harms or lack ofbenefit in the context of a patient s overall status and goals and preferences for care. Patient Priorities Care (PPC) is an evidence- based approach to identify outcome goals and care preferences (health priorities) and align care to meet those priorities. Deprescribing is targeted towards therapies that are misaligned with priorities. Less is known about how PPC works in thecontext of clinician, caregiver, and persons living with dementia (PlwD). Aligning all three goals could be crucial for successful, safe deprescribing in the setting of dementia. To facilitate the adaptation of the PPC approach to the context of deprescribing for PlwD, we will address the following research questions: Q1) How does the identification of patient priorities facilitate deprescribing for PlwD and their caregivers Q2) How are blended (PlwD and caregiver) outcome goals and caregivers care preferences interpreted and used by clinicians Q3) How do clinicians make treatment decisions to reduce or stop medications based on the misalignment of drugs with priorities that include blended outcome goals and caregiver preferences Q4) What are the adverse drug withdrawal events (ADWEs) that occur from deprescribing medications based on patient priorities aligned care decisions To answer these questions, we propose the following study aims: Aim 1: Conduct a pilot randomized clinical trialwith 50 PlwD and caregiver dyads and their clinicians to compare the PPC approach and usual care to identify differences in post-encounter medication changes, treatment burden, and shared decision making. We will also compare differences in medication changes based on documentation of care preferences and goals by patients, caregivers, or both. (Q1) Aim 2: For PPC participants, we will conduct cognitive-task-analyses with primary providers to understandtheir sense-making and communication approaches related to deprescribing decisions in relation to the identified health priorities. (Q2, Q3) Aim 3: For all participants, we will conduct a post-encounter follow up televisit to identify and categorize ADWEs. (Q4) The study results willinform the processes of how clinicians make decisions about medication misalignment with priorities and the extent to which those decisions result in ADWE. Findings will also provide feasibility and effect size data to inform a larger clinical trial of Patient Priorities Care, testing itseffectiveness and safety for deprescribing for PlwD and their caregivers.
 
20. Project Title: UNINTENDED PROLONGED OPIOID USE
  Leader(s): HOOTEN, W. MICHAEL
    MAYO CLINIC
    NIH U01TR002743 / ( 2019 - 2023 )
  Core(s):
  PROJECT SUMMARYMisuse of prescription opioids remains a public health crisis. Appropriate short-term use of these medicationsin opioid-na ve patients is indicated in select health care settings, but intentional short-term use is emerging asa previously under-recognized segue to unintended prolonged opioid use (UPOU). Clinical strategies aimed atpreventing UPOU in health care settings are lacking due, in part, to absence of information about how thispoorly-understood clinical phenomenon develops.Investigators at Mayo Clinic recently organized a group of thought leaders to develop a conceptual frameworkto explain UPOU. Such a framework is essential both to guide the study of this problem and to identify potentialtargets for interventions to reduce UPOU. The framework is comprised of three domains, including (1) patientcharacteristics; (2) practice environment characteristics; and (3) opioid prescriber characteristics that interact toeither facilitate or impede UPOU. Within each domain, potential factors, drawn from the relevant literature,moderate or mediate the influence of each domain. However, much of the information needed to evaluate thisframework does not currently exist. The widespread adoption of electronic health records (EHR) providesunique potential opportunities for translational research, including identifying subjects eligible for studyparticipation and serving as a data sources for retrospective or prospective studies. However, interoperabilitybetween EHRs poses a considerable challenge to taking advantage of these opportunities.Researchers at the Yale School of Medicine recently launched Hugo, a secure mobile personal health(mHealth) platform that enables patients to access their information from multiple EHRs and other healthcareinformation sources, including commercial pharmacy records. The Hugo platform has tremendous potential tofacilitate clinical research, especially research conducted across multiple centers as information from diversesource systems at each institution can be easily integrated into a common dataset.In this application, four CTSA hubs (Mayo Clinic, University of Minnesota, University of Michigan, and Yale) willexplore the Hugo platform's potential to facilitate clinical research, with the UPOU study as a use case. We willuse the Hugo platform to identify incident cases of UPOU and prospectively recruit patients and opioidprescribers for assessments, as well as to evaluate the proposed conceptual framework using structuralequation models. At this study's conclusion, we will have successfully deployed a highly innovative mHealthplatform across multiple centers and this platform will be immediately available for widespread disseminationacross the entire CTSA consortium and other clinical research sites. The information gained about UPOU willsignificantly advance core knowledge about this poorly understood clinical phenomenon. This newly acquiredinformation will be used design, test, and deploy prevention strategies aimed at mitigating the risks of UPOU.
 
21. Project Title: PAIN MANAGEMENT COLLABORATORY COORDINATING CENTER (PMC3)
  Leader(s): KERNS, ROBERT D; BRANDT, CYNTHIA A. ; PEDUZZI, PETER NATALE ;
    YALE UNIVERSITY
    NIH U24AT009769 / ( 2017 - 2023 )
  Core(s):
  Project Summary / AbstractThe Pain Management Collaboratory Coordinating Center (PMC3) will (1) provide national leadership andtechnical expertise in all aspects of research supporting the design and execution of high impactDemonstration Projects that conduct cost-effective, large-scale, pragmatic clinical trials on non-pharmacological approaches for pain management and other comorbid conditions in veteran or military healthcare systems, and (2) make data, tools, best practices, and resources from these and other projects availableto facilitate research partnerships in VA and DoD health systems. The PMC3 will leverage the expertise of thePain Research, Informatics, Multimorbidities and Education (PRIME) Center of Innovation based at the VAConnecticut Healthcare System (VACHS) and its partners at VACHS and Yale, including the VA CooperativeStudies Program Coordinating Center/Clinical Epidemiology Research Center and the Yale Center forAnalytical Sciences and Yale Center for Medical Informatics, enhanced by a strong partnership with colleaguesat the Uniformed Services University for the Health Sciences Center for Rehabilitation Sciences Research anda novel Military Treatment Facility Engagement Committee comprised of collaborating DoD and universityaffiliated investigators, clinicians and educators devoted to facilitating successful pragmatic trials in DoDsettings. We will use our expertise in pain management, electronic health records (EHR), data systems and thedesign and coordination of multi-site pragmatic trials to accomplish these objectives in collaboration with ourVA, DoD and Yale partners. To achieve these objectives, three specific sims will be addressed: Aim 1: Todevelop, adapt and adopt technical policy guidelines and best practices for the effective design and conduct ofpragmatic trials; Aim 2: To work collaboratively with and provide operational, technical, design and othersupport to Demonstration Project teams to develop, initiate and implement a research protocol; and Aim 3:Towidely disseminate NIH-DoD-VA Pain Management Collaboratory endorsed policies and best practices andlessons learned within military and veteran health care systems. Achievement of these objectives and SpecificAims promise to significantly accelerate the integration of evidence-based non-pharmacological approaches forthe management of pain into routine clinical care in military and veteran health care systems consistent withkey recommendations from the National Pain Strategy.
 
22. Project Title: NIA AD/ADRD HEALTH CARE SYSTEMS RESEARCH COLLABORATORY
  Leader(s): MOR, VINCENT; MITCHELL, SUSAN L ;
    BROWN UNIVERSITY
    NIH U54AG063546 / ( 2019 - 2024 )
  Core(s):
  PROJECT SUMMARYOver five million Americans have Alzheimer's disease (AD) or an AD-related dementia (AD/ADRD). These high-need, high-cost patients are vulnerable to receiving poor quality, uncoordinated care, ultimately leading toadverse health outcomes, poor quality of life, and misuse of resources. As recently concluded by the federally-funded Research Summit on Dementia Care, improving the care of PWD and their CGs is an urgent public healthchallenge that must be met and informed by high quality evidence. While prior research has elucidatedopportunities to improve the care of PWD and their CGs, the adoption of promising interventions has beenstymied by the lack of research evaluating their effectiveness when implemented under real-world conditions.Pragmatic clinical trials embedded (ePCTs) in healthcare systems (HCS) have the potential to accelerate thetranslation of evidence-based interventions into clinical practice. Since its inception in 2012, the NIH CommonFund HCS Research Collaboratory has made pivotal contributions towards advancing the conduct of ePCTs.However, as concluded in a 2017 NIA-sponsored conference, ePCTs conducted with PWD and their CGs haveunique considerations that merit specific focus. Thus, the overarching objective of this proposal is to build on themodel of the NIH Collaboratory to establish the National Institute on Aging (NIA) AD/ADRD ResearchCollaboratory, co-led by the multiple principal investigators (MPIs), Drs. Vince Mor (Brown University) and SusanMitchell (Hebrew SeniorLife (HSL)) and co-administered by their respective institutions. The Aims are: 1. Toestablish the infrastructure of the AD/ADRD Collaboratory, 2. To develop and disseminate guidelines for theconduct of all aspects of ePCTs among PWD and their CGs in partnership with HCS, 3. Enhance researchdevelopment and investigator capacity to conduct ePCTs in PWD and their CGs within HCS, and 4. Todisseminate knowledge and best practices to engage stakeholders in this research. Accomplished investigatorsfrom across the nation will lead the following Working Group Cores: 1. Technical and Data (B), J. Bynum, MD,MPH; 2. Regulation and Ethics (C), J. Karlawish, MD; 3. Design and Statistics (D), H. Allore, PhD; 4. Pilot Studies(E), A. Brody, PhD, RN; 5. Patient and CG Reported Outcomes (F), L. Hanson, MD, MPH; 6. Dissemination andImplementation (G), L. Gitlin, PhD/J. Gaugler, PhD; 7. HCS (H): E. Larson, MD, MPH, and Training (I): C.Callahan MD/A. Torke MD. An Administration Core (A) will integrate all critical functions across the Collaboratory.IMPACT: There is an urgent need to improve care provided by HCS for PWD and their CGs. ePCTs conductedare ideally-suited to test the effectiveness of interventions aimed at improving their health outcomes but requirespecific expertise, methodology, data sources, and industry partnerships. The knowledge, investigativeexperience, collaborations, and evidence generated by an AD/ADRD Collaboratory has the potential to transformthe delivery, quality, and outcomes of care for Americans from all backgrounds with AD/ADRD and their CGs.
 
PUBLICATIONS
2022
  1. Analysis of Clinical Traits Associated With Cardiovascular Health, Genomic Profiles, and Neuroimaging Markers of Brain Health in Adults Without Stroke or Dementia.
    Acosta JN, Both CP, Rivier C, Szejko N, Leasure AC, Gill TM, Payabvash S, Sheth KN, Falcone GJ
    JAMA Netw Open, 2022 May 2, 5(5): e2215328
    https://doi.org/10.1001/jamanetworkopen.2022.15328 | PMID: 35622359 | PMCID: PMC9142873
    Citations: | AltScore: 25.732
  2. Genetically Determined Low-Density Lipoprotein Cholesterol and Risk of Subarachnoid Hemorrhage.
    Acosta JN, Both CP, Szejko N, Leasure AC, Abdelhakim S, Torres-Lopez VM, Brown SC, Matouk CC, Gunel M, Sheth KN, Falcone GJ
    Ann Neurol, 2022 Jan, 91(1): 145-149
    https://doi.org/10.1002/ana.26250 | PMID: 34709661
    Citations: | AltScore: 11.25
  3. Patterns of Caregiving Among Older Adults With and Without Dementia: A Latent Class Analysis.
    Ali T, McAvay GJ, Monin JK, Gill TM
    J Gerontol B Psychol Sci Soc Sci, 2022 May 20, 77(Suppl_1): S74-S85
    https://doi.org/10.1093/geronb/gbab237 | PMID: 35032392 | PMCID: PMC9122635
    Citations: 1 | AltScore: 4.8
  4. CT angiographic radiomics signature for risk stratification in anterior large vessel occlusion stroke.
    Avery EW, Behland J, Mak A, Haider SP, Zeevi T, Sanelli PC, Filippi CG, Malhotra A, Matouk CC, Griessenauer CJ, Zand R, Hendrix P, Abedi V, Falcone GJ, Petersen N, Sansing LH, Sheth KN, Payabvash S
    Neuroimage Clin, 2022, 34: 103034
    https://doi.org/10.1016/j.nicl.2022.103034 | PMID: 35550243 | PMCID: PMC9108990
    Citations: | AltScore: 10.1
  5. Sex Differences in Symptom Phenotypes Among Older Patients with Acute Myocardial Infarction.
    Brush JE Jr, Hajduk AM, Greene EJ, Dreyer RP, Krumholz HM, Chaudhry SI
    Am J Med, 2022 Mar, 135(3): 342-349
    https://doi.org/10.1016/j.amjmed.2021.09.022 | PMID: 34715061 | PMCID: PMC8901454
    Citations: 1 | AltScore: 4
  6. Life course traumas and cardiovascular disease-The mediating role of accelerated aging.
    Cao X, Zhang J, Ma C, Li X, Kuo CL, Levine ME, Hu G, Allore H, Chen X, Wu X, Liu Z
    Ann N Y Acad Sci, 2022 Jun 20
    https://doi.org/10.1111/nyas.14843 | PMID: 35725988
    Citations: | AltScore: 9.5
  7. Risk Factors of Skilled Nursing Facility Admissions and the Interrelation With Hospitalization and Amount of Informal Caregiving Received.
    Cao Y, Allore H, Gutman R, Vander Wyk B, J?rgensen TSH
    Med Care, 2022 Apr 1, 60(4): 294-301
    https://doi.org/10.1097/MLR.0000000000001697 | PMID: 35149662 | PMCID: PMC8916995
    Citations: | AltScore: 6.1
  8. Difficulty and help with activities of daily living among older adults living alone during the COVID-19 pandemic: a multi-country population-based study.
    Chen S, Jones LA, Jiang S, Jin H, Dong D, Chen X, Wang D, Zhang Y, Xiang L, Zhu A, Cardinal RN
    BMC Geriatr, 2022 Mar 4, 22(1): 181
    https://doi.org/10.1186/s12877-022-02799-w | PMID: 35246064 | PMCID: PMC8894568
    Citations: 2 | AltScore: 4.3
  9. Key links in network interactions: Assessing route-specific travel restrictions in China during the Covid-19 pandemic.
    Chen X, Qiu Y, Shi W, Yu P
    China Econ Rev, 2022 Apr 20, 73: 101800
    https://doi.org/10.1016/j.chieco.2022.101800 | PMID: 35469340 | PMCID: PMC9020714
    Citations: | AltScore: 3.7
  10. Childhood Circumstances and Health Inequality in Old Age: Comparative Evidence from China and the USA.
    Chen X, Yan B, Gill TM
    Soc Indic Res, 2022 Apr, 160(2-3): 689-716
    https://doi.org/10.1007/s11205-020-02436-2 | PMID: 35359349 | PMCID: PMC8963775
    Citations: | AltScore: 6.15
  11. New horizons in evidence-based care for older people: individual participant data meta-analysis.
    Clegg A, Bandeen-Roche K, Farrin A, Forster A, Gill TM, Gladman J, Kerse N, Lindley R, McManus RJ, Melis R, Mujica-Mota R, Raina P, Rockwood K, Teh R, van der Windt D, Witham M
    Age Ageing, 2022 Apr 1, 51(4):
    pii: afac090. https://doi.org/10.1093/ageing/afac090 | PMID: 35460409 | PMCID: PMC9034697
    Citations: | AltScore: 49.93
  12. Trends in Geriatric Conditions Among Older Adults Admitted to US ICUs Between 1998 and 2015.
    Cobert J, Jeon SY, Boscardin J, Chapman AC, Ferrante LE, Lee S, Smith AK
    Chest, 2022 Jan 11, 161(6): 1555-1565
    pii: S0012-3692(22)00020-4. https://doi.org/10.1016/j.chest.2021.12.658 | PMID: 35026299 | PMCID: PMC9248079
    Citations: 1 | AltScore: 30.04
  13. Rehabilitation Using Mobile Health for Older Adults With Ischemic Heart Disease in the Home Setting (RESILIENT): Protocol for a Randomized Controlled Trial.
    Dodson JA, Schoenthaler A, Sweeney G, Fonceva A, Pierre A, Whiteson J, George B, Marzo K, Drewes W, Rerisi E, Mathew R, Aljayyousi H, Chaudhry SI, Hajduk AM, Gill TM, Estrin D, Kovell L, Jennings LA, Adhikari S
    JMIR Res Protoc, 2022 Mar 3, 11(3): e32163
    https://doi.org/10.2196/32163 | PMID: 35238793 | PMCID: PMC8931649
    Citations: | AltScore: 2.25
  14. Enhancing cosinor analysis of circadian phase markers using the gamma distribution.
    Doyle MM, Murphy TE, Miner B, Pisani MA, Lusczek ER, Knauert MP
    Sleep Med, 2022 Apr, 92: 1-3
    https://doi.org/10.1016/j.sleep.2022.01.015 | PMID: 35306404
    Citations: | AltScore: 4.5
  15. Association of Financial Strain With Mortality Among Older US Adults Recovering From an Acute Myocardial Infarction.
    Falvey JR, Hajduk AM, Keys CR, Chaudhry SI
    JAMA Intern Med, 2022 Apr 1, 182(4): 445-448
    https://doi.org/10.1001/jamainternmed.2021.8569 | PMID: 35188537 | PMCID: PMC8861896
    Citations: | AltScore: 194.25
  16. Neighborhood Socioeconomic Disadvantage and Disability After Critical Illness.
    Falvey JR, Murphy TE, Leo-Summers L, Gill TM, Ferrante LE
    Crit Care Med, 2022 May 1, 50(5): 733-741
    https://doi.org/10.1097/CCM.0000000000005364 | PMID: 34636807 | PMCID: PMC9001742
    Citations: 1 | AltScore: 32.95
  17. Long-term ozone exposure and cognitive impairment among Chinese older adults: A cohort study.
    Gao Q, Zang E, Bi J, Dubrow R, Lowe SR, Chen H, Zeng Y, Shi L, Chen K
    Environ Int, 2022 Feb, 160: 107072
    https://doi.org/10.1016/j.envint.2021.107072 | PMID: 34979350 | PMCID: PMC8821373
    Citations: | AltScore: 29.5
  18. Emergency department-to-community care transition barriers: A qualitative study of older adults.
    Gettel CJ, Serina PT, Uzamere I, Hernandez-Bigos K, Venkatesh AK, Rising KL, Goldberg EM, Feder SL, Cohen AB, Hwang U
    J Am Geriatr Soc, 2022 Jul 2
    https://doi.org/10.1111/jgs.17950 | PMID: 35779278
    Citations: | AltScore: 24.7
  19. Pragmatic clinical trial design in emergency medicine: Study considerations and design types.
    Gettel CJ, Yiadom MYAB, Bernstein SL, Grudzen CR, Nath B, Li F, Hwang U, Hess EP, Melnick ER
    Acad Emerg Med, 2022 Apr 27
    https://doi.org/10.1111/acem.14513 | PMID: 35475533
    Citations: | AltScore: 14.95
  20. Geriatric vulnerability and the burden of disability after major surgery.
    Gill TM, Murphy TE, Gahbauer EA, Leo-Summers L, Becher RD
    J Am Geriatr Soc, 2022 May, 70(5): 1471-1480
    https://doi.org/10.1111/jgs.17693 | PMID: 35199332 | PMCID: PMC9106872
    Citations: | AltScore: 100.4
  21. Factors Associated With Cardiac Rehabilitation Participation in Older Adults After Myocardial Infarction: THE SILVER-AMI STUDY.
    Goldstein DW, Hajduk AM, Song X, Tsang S, Geda M, Dodson JA, Forman DE, Krumholz H, Chaudhry SI
    J Cardiopulm Rehabil Prev, 2022 Mar 1, 42(2): 109-114
    https://doi.org/10.1097/HCR.0000000000000627 | PMID: 34799530 | PMCID: PMC8881286
    Citations: | AltScore: 4.6
  22. Reply to: \Comment on: Falls in older adults after hospitalization for acute myocardial infarction\.
    Goldstein DW, Hajduk AM, Song X, Tsang S, Geda M, McClurken JB, Tinetti ME, Krumholz HM, Chaudhry SI
    J Am Geriatr Soc, 2022 Mar 24, 70(6): 1880-1881
    https://doi.org/10.1111/jgs.17742 | PMID: 35332528 | PMCID: PMC9177624
    Citations: | AltScore: NA
  23. The importance of chronic conditions for potentially avoidable hospitalizations among non-Hispanic Black and non-Hispanic White older adults in the US: a cross-sectional observational study.
    J?rgensen TSH, Allore H, Elman MR, Nagel C, Qui?ones AR
    BMC Health Serv Res, 2022 Apr 9, 22(1): 468
    https://doi.org/10.1186/s12913-022-07849-y | PMID: 35397539 | PMCID: PMC8994911
    Citations: | AltScore: 1
  24. Association Between Socioeconomic Disadvantage and Decline in Function, Cognition, and Mental Health After Critical Illness Among Older Adults : A Cohort Study.
    Jain S, Murphy TE, O'Leary JR, Leo-Summers L, Ferrante LE
    Ann Intern Med, 2022 May, 175(5): 644-655
    https://doi.org/10.7326/M21-3086 | PMID: 35254879 | PMCID: PMC9316386
    Citations: | AltScore: 172.63
  25. Association between Residential Segregation and Long-Term Acute Care Hospital Performance on Improvement in Function among Ventilated Patients.
    Jain S, Walkey AJ, Law AC, Ferrante LE, Lindenauer PK, Krumholz HM
    Ann Am Thorac Soc, 2022 Jan, 19(1): 147-150
    https://doi.org/10.1513/AnnalsATS.202107-796RL | PMID: 34644244 | PMCID: PMC8787797
    Citations: | AltScore: 18.9
  26. Modeling success: How to work effectively with your biostatistician.
    Lee J, Kamdar BB, Bergstrom J, Murphy TE, Gill TM
    J Am Geriatr Soc, 2022 May 24
    https://doi.org/10.1111/jgs.17888 | PMID: 35608207
    Citations: | AltScore: 31.95
  27. Perceived dementia risk and advance care planning among older adults.
    Lee YK, Fried TR, Costello DM, Hajduk AM, O'Leary JR, Cohen AB
    J Am Geriatr Soc, 2022 May, 70(5): 1481-1486
    https://doi.org/10.1111/jgs.17721 | PMID: 35274737 | PMCID: PMC9106856
    Citations: | AltScore: 13.25
  28. Occupations and Sickness-Related Absences during the COVID-19 Pandemic.
    Lyttelton T, Zang E
    J Health Soc Behav, 2022 Mar, 63(1): 19-36
    https://doi.org/10.1177/00221465211053615 | PMID: 35100514 | PMCID: PMC9013443
    Citations: | AltScore: 32.2
  29. Preclinical frailty assessments: Phenotype and frailty index identify frailty in different mice and are variably affected by chronic medications.
    Mach J, Allore H, Gnjidic D, Gemikonakli G, Kane AE, Howlett SE, de Cabo R, Le Couteur D, Hilmer SN
    Exp Gerontol, 2022 May, 161: 111700
    https://doi.org/10.1016/j.exger.2022.111700 | PMID: 35032570
    Citations: | AltScore: 4.25
  30. Cerebral Microbleeds and Acute Hematoma Characteristics in the ATACH-2 and MISTIE III Trials.
    Magid-Bernstein JR, Li Y, Cho SM, Piran PJ, Roh DJ, Gupta A, Shoamanesh A, Merkler A, Zhang C, Avadhani R, Montano N, Iadecola C, Falcone GJ, Sheth KN, Qureshi AI, Rosand J, Goldstein J, Awad I, Hanley DF, Kamel H, Ziai WC, Murthy SB
    Neurology, 2022 Mar 8, 98(10): e1013-e1020
    https://doi.org/10.1212/WNL.0000000000013247 | PMID: 34937780 | PMCID: PMC8967392
    Citations: | AltScore: 8.3
  31. Association of entorhinal cortical tau deposition and hippocampal synaptic density in older individuals with normal cognition and early Alzheimer's disease.
    Mecca AP, Chen MK, O'Dell RS, Naganawa M, Toyonaga T, Godek TA, Harris JE, Bartlett HH, Zhao W, Banks ER, Ni GS, Rogers K, Gallezot JD, Ropchan J, Emery PR, Nabulsi NB, Vander Wyk BC, Arnsten AFT, Huang Y, Carson RE, van Dyck CH
    Neurobiol Aging, 2022 Mar, 111: 44-53
    https://doi.org/10.1016/j.neurobiolaging.2021.11.004 | PMID: 34963063 | PMCID: PMC8761170
    Citations: 1 | AltScore: 10
  32. Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [11 C]UCB-J.
    Mecca AP, O'Dell RS, Sharp ES, Banks ER, Bartlett HH, Zhao W, Lipior S, Diepenbrock NG, Chen MK, Naganawa M, Toyonaga T, Nabulsi NB, Vander Wyk BC, Arnsten AFT, Huang Y, Carson RE, van Dyck CH
    Alzheimers Dement, 2022 Feb 17
    https://doi.org/10.1002/alz.12582 | PMID: 35174954
    Citations: 2 | AltScore: 65.506
  33. Self-reported and actigraphic short sleep duration in older adults.
    Miner B, Stone KL, Zeitzer JM, Han L, Doyle M, Blackwell T, Gill TM, Redeker NS, Hajduk A, Yaggi HK
    J Clin Sleep Med, 2022 Feb 1, 18(2): 403-413
    https://doi.org/10.5664/jcsm.9584 | PMID: 34338629 | PMCID: PMC8804982
    Citations: 2 | AltScore: 7.9
  34. Clin-Star corner: A new series featuring practice-changing articles in medical, surgical, and related specialties.
    Mody L, Gill TM, Zieman SJ
    J Am Geriatr Soc, 2022 Jun 15
    https://doi.org/10.1111/jgs.17908 | PMID: 35704905
    Citations: | AltScore: 14.45
  35. A Controlled Pilot Study of the Wish Outcome Obstacle Plan Strategy for Spouses of Persons With Early-Stage Dementia.
    Monin JK, Oettingen G, Laws H, David D, DeMatteo L, Marottoli R
    J Gerontol B Psychol Sci Soc Sci, 2022 Mar 3, 77(3): 513-524
    https://doi.org/10.1093/geronb/gbab115 | PMID: 34171086 | PMCID: PMC8893137
    Citations: | AltScore: 11.85
  36. Sleep Deficiency in the Elderly.
    Pappas JA, Miner B
    Clin Chest Med, 2022 Jun, 43(2): 273-286
    https://doi.org/10.1016/j.ccm.2022.02.005 | PMID: 35659025
    Citations: | AltScore: 0.75
  37. Risk of Mortality After an Arterial Ischemic Event Among Intracerebral Hemorrhage Survivors.
    Parasram M, Parikh NS, Merkler AE, Falcone GJ, Sheth KN, Navi BB, Kamel H, Zhang C, Murthy SB
    Neurohospitalist, 2022 Jan, 12(1): 19-23
    https://doi.org/10.1177/19418744211026709 | PMID: 34950382 | PMCID: PMC8689534
    Citations: 1 | AltScore: 5.75
  38. Trajectories of cognitive functioning in later life: Disparities by race/ethnicity, educational attainment, sex, and multimorbidity combinations.
    Qui?ones AR, Chen S, Nagel CL, Botoseneanu A, Allore HG, Newsom JT, Thielke S, Kaye J
    SSM Popul Health, 2022 Jun, 18: 101084
    https://doi.org/10.1016/j.ssmph.2022.101084 | PMID: 35402685 | PMCID: PMC8987641
    Citations: | AltScore: 3.1
  39. Compromised Cardiopulmonary Function in Fibulin-5 Deficient Mice.
    Ramachandra AB, Mikush N, Sauler M, Humphrey JD, Manning EP
    J Biomech Eng, 2022 Aug 1, 144(8):
    pii: 081008. https://doi.org/10.1115/1.4053873 | PMID: 35171214 | PMCID: PMC8990734
    Citations: | AltScore: 2.35
  40. Characterization of the COPD alveolar niche using single-cell RNA sequencing.
    Sauler M, McDonough JE, Adams TS, Kothapalli N, Barnthaler T, Werder RB, Schupp JC, Nouws J, Robertson MJ, Coarfa C, Yang T, Chioccioli M, Omote N, Cosme C Jr, Poli S, Ayaub EA, Chu SG, Jensen KH, Gomez JL, Britto CJ, Raredon MSB, Niklason LE, Wilson AA, Timshel PN, Kaminski N, Rosas IO
    Nat Commun, 2022 Jan 25, 13(1): 494
    https://doi.org/10.1038/s41467-022-28062-9 | PMID: 35078977 | PMCID: PMC8789871
    Citations: 4 | AltScore: 168.156
  41. Polypharmacy in older adults with HIV infection: Effects on the brain.
    Smith L, Letendre S, Erlandson KM, Ma Q, Ellis RJ, Farhadian SF
    J Am Geriatr Soc, 2022 Mar, 70(3): 924-927
    https://doi.org/10.1111/jgs.17569 | PMID: 34855982 | PMCID: PMC8904273
    Citations: | AltScore: 5.05
  42. Intrinsic Capacity Predicts Negative Health Outcomes in Older Adults.
    Stolz E, Mayerl H, Freidl W, Roller-Wirnsberger R, Gill TM
    J Gerontol A Biol Sci Med Sci, 2022 Jan 7, 77(1): 101-105
    https://doi.org/10.1093/gerona/glab279 | PMID: 34569602 | PMCID: PMC8751795
    Citations: 1 | AltScore: 17.4
  43. Genetically-Proxied Levels of Vitamin D and Risk of Intracerebral Hemorrhage.
    Szejko N, Acosta JN, Both CP, Leasure A, Matouk C, Sansing L, Gill TM, Hongyu Z, Sheth K, Falcone GJ
    J Am Heart Assoc, 2022 Jul 5, 11(13): e024141
    https://doi.org/10.1161/JAHA.121.024141 | PMID: 35730641 | PMCID: PMC9333362
    Citations: | AltScore: 1.25
  44. The geriatrics research instrument library: A resource for guiding instrument selection for researchers studying older adults with multiple chronic conditions.
    Tisminetzky M, Delude C, Allore HG, Anzuoni K, Bloomstone S, Charpentier P, Hepler JP, Kitzman DW, McAvay GJ, Miller M, Pajewski NM, Gurwitz J
    J Multimorb Comorb, 2022, 12: 26335565221081200
    https://doi.org/10.1177/26335565221081200 | PMID: 35586036 | PMCID: PMC9106318
    Citations: | AltScore: 2
  45. Trajectories of General Health Status and Depressive Symptoms Among Persons With Cognitive Impairment in the United States.
    Zang E, Guo A, Pao C, Lu N, Wu B, Fried TR
    J Aging Health, 2022 Jan 18 8982643211060948
    https://doi.org/10.1177/08982643211060948 | PMID: 35040695 | PMCID: PMC9289075
    Citations: | AltScore: 19.4
  46. Trajectories of physical functioning among US adults with cognitive impairment.
    Zang E, Shi Y, Wang X, Wu B, Fried TR
    Age Ageing, 2022 Jun 1, 51(6):
    pii: afac139. https://doi.org/10.1093/ageing/afac139 | PMID: 35751871 | PMCID: PMC9233517
    Citations: | AltScore: 9
  47. Bayesian network mediation analysis with application to the brain functional connectome.
    Zhao Y, Chen T, Cai J, Lichenstein S, Potenza M, Yip S
    Stat Med, 2022 Jul 6
    https://doi.org/10.1002/sim.9488 | PMID: 35795965
    Citations: | AltScore: NA
 
2021
  1. Risk factors for injuries in New Zealand older adults with complex needs: a national population retrospective study.
    Abey-Nesbit R, Schluter PJ, Wilkinson TJ, Thwaites JH, Berry SD, Allore H, Jamieson HA
    BMC Geriatr, 2021 Nov 4, 21(1): 630
    https://doi.org/10.1186/s12877-021-02576-1 | PMID: 34736406 | PMCID: PMC8567659
    Citations: | AltScore: 2
  2. Factors associated with caregiver distress among home care clients in New Zealand: Evidence based on data from interRAI Home Care assessment.
    Abey-Nesbit R, Van Doren S, Ahn S, Iheme L, Peel NM, Declercq A, Hirdes J, Allore H, Jamieson HA
    Australas J Ageing, 2021 Nov 27, 41(2): 237-246
    https://doi.org/10.1111/ajag.13011 | PMID: 34837288
    Citations: | AltScore: 1
  3. Development and usability evaluation of VOICES: A digital health tool to identify elder mistreatment.
    Abujarad F, Ulrich D, Edwards C, Choo E, Pantalon MV, Jubanyik K, Dziura J, D'Onofrio G, Gill TM
    J Am Geriatr Soc, 2021 Jun, 69(6): 1469-1478
    https://doi.org/10.1111/jgs.17068 | PMID: 33615433 | PMCID: PMC8192463
    Citations: 1 | AltScore: 33.4
  4. Cardiovascular Health Disparities in Racial and Other Underrepresented Groups: Initial Results From the All of Us Research Program.
    Acosta JN, Leasure AC, Both CP, Szejko N, Brown S, Torres-Lopez V, Abdelhakim S, Schindler J, Petersen N, Sansing L, Gill TM, Sheth KN, Falcone GJ
    J Am Heart Assoc, 2021 Sep 7, 10(17): e021724
    https://doi.org/10.1161/JAHA.121.021724 | PMID: 34431358 | PMCID: PMC8649271
    Citations: 2 | AltScore: 17.55
  5. Admission Hemoglobin Levels Are Associated With Functional Outcome in Spontaneous Intracerebral Hemorrhage.
    Acosta JN, Leasure AC, Kuohn LR, Both CP, Petersen NH, Sansing LH, Matouk CC, Testai F, Langefeld CD, Woo D, Kamel H, Murthy SB, Qureshi A, Mayer SA, Sheth KN, Falcone GJ
    Crit Care Med, 2021 May 1, 49(5): 828-837
    https://doi.org/10.1097/CCM.0000000000004891 | PMID: 33591003 | PMCID: PMC8611893
    Citations: 3 | AltScore: 13.6
  6. Genetically Determined Smoking Behavior and Risk of Nontraumatic Subarachnoid Hemorrhage.
    Acosta JN, Szejko N, Both CP, Vanent K, Noche RB, Gill TM, Matouk CC, Sheth KN, Gunel M, Falcone GJ
    Stroke, 2021 Jan, 52(2): 582-587
    https://doi.org/10.1161/STROKEAHA.120.031622 | PMID: 33440997 | PMCID: PMC7856108
    Citations: 2 | AltScore: 114.35
  7. Association Between Potentially Inappropriate Medications and 30-Day Post-Hospital Discharge Outcomes in US Veterans.
    Allore HG, Gnjidic D, Skanderson M, Han L
    Ann Pharmacother, 2021 Jul 20, 56(3): 256-263
    https://doi.org/10.1177/10600280211032072 | PMID: 34282638 | PMCID: PMC8770754
    Citations: | AltScore: 3.1
  8. Andexanet Alfa Versus 4-Factor Prothrombin Complex Concentrate for Reversal of Factor Xa Inhibitors in Intracranial Hemorrhage.
    Ammar AA, Ammar MA, Owusu KA, Brown SC, Kaddouh F, Elsamadicy AA, Acosta JN, Falcone GJ
    Neurocrit Care, 2021 Aug, 35(1): 255-261
    https://doi.org/10.1007/s12028-020-01161-5 | PMID: 33403588
    Citations: 5 | AltScore: 51.8
  9. Elevated IL-6 and CRP Levels Are Associated With Incident Self-Reported Major Mobility Disability: A Pooled Analysis of Older Adults With Slow Gait Speed.
    Beavers DP, Kritchevsky SB, Gill TM, Ambrosius WT, Anton SD, Fielding RA, King AC, Rejeski WJ, Lovato L, McDermott MM, Newman AB, Pahor M, Walkup MP, Tracy RP, Manini TM
    J Gerontol A Biol Sci Med Sci, 2021 Nov 15, 76(12): 2293-2299
    https://doi.org/10.1093/gerona/glab093 | PMID: 33822946 | PMCID: PMC8598983
    Citations: | AltScore: 4.5
  10. The Incidence and Cumulative Risk of Major Surgery in Older Persons in the United States.
    Becher RD, Wyk BV, Leo-Summers L, Desai MM, Gill TM
    Ann Surg, 2021 Jul 14
    https://doi.org/10.1097/SLA.0000000000005077 | PMID: 34261884 | PMCID: PMC8758792
    Citations: 1 | AltScore: 10.25
  11. Metabolic syndrome and the benefit of a physical activity intervention on lower-extremity function: Results from a randomized clinical trial.
    Botoseneanu A, Chen H, Ambrosius WT, Allore HG, Anton S, Folta SC, King AC, Nicklas BJ, Spring B, Strotmeyer ES, Gill TM
    Exp Gerontol, 2021 Jul 15, 150: 111343
    https://doi.org/10.1016/j.exger.2021.111343 | PMID: 33848565 | PMCID: PMC8388825
    Citations: 2 | AltScore: 5.45
  12. Ratings of Perceived Exertion During Walking: Predicting Major Mobility Disability and Effect of Structured Physical Activity in Mobility-Limited Older Adults.
    Cenko E, Chen H, Gill TM, Glynn NW, Henderson RM, King AC, Pahor M, Qiu P, Rego A, Reid KF, Tudor-Locke C, Valiani V, You L, Manini TM
    J Gerontol A Biol Sci Med Sci, 2021 Sep 13, 76(10): e264-e271
    https://doi.org/10.1093/gerona/glab036 | PMID: 33585918 | PMCID: PMC8436976
    Citations: | AltScore: 3.25
  13. Failure Mode and Effect Analysis: Engineering Safer Neurocritical Care Transitions.
    Chilakamarri P, Finn EB, Sather J, Sheth KN, Matouk C, Parwani V, Ulrich A, Davis M, Pham L, Chaudhry SI, Venkatesh AK
    Neurocrit Care, 2021 Jan 5, 35(1): 232-240
    https://doi.org/10.1007/s12028-020-01160-6 | PMID: 33403581 | PMCID: PMC8255326
    Citations: | AltScore: 3.35
  14. How should advance care planning be done when a surrogate is making decisions?
    Cohen AB, DeMartino ES
    J Am Geriatr Soc, 2021 Aug, 69(8): 2103-2105
    https://doi.org/10.1111/jgs.17222 | PMID: 34002373 | PMCID: PMC8373712
    Citations: | AltScore: 3.25
  15. Guardianship and End-of-Life Care for Veterans with Dementia in Nursing Homes.
    Cohen AB, Han L, O'Leary JR, Fried TR
    J Am Geriatr Soc, 2021 Feb, 69(2): 342-348
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  16. Characteristics of Older Adults Who Cannot Identify a Healthcare Agent.
    Cohen AB, Paiva AL, Redding CA, Fried TR
    J Gen Intern Med, 2021 Apr 26, 37(5): 1313-1314
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  17. Education needed to improve antimicrobial use during end-of-life care of older adults with advanced cancer: A cross-sectional survey.
    Datta R, Topal J, McManus D, Sanft T, Dembry LM, Morrison LJ, Quagliarello V, Juthani-Mehta M
    Palliat Med, 2021 Jan, 35(1): 236-241
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  18. 180-day readmission risk model for older adults with acute myocardial infarction: the SILVER-AMI study.
    Dodson JA, Hajduk AM, Murphy TE, Geda M, Krumholz HM, Tsang S, Nanna MG, Tinetti ME, Ouellet G, Sybrant D, Gill TM, Chaudhry SI
    Open Heart, 2021 Jan, 8(1):
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  19. A SAS macro for modelling periodic data using cosinor analysis.
    Doyle MM, Murphy TE, Pisani MA, Yaggi HK, Jeon S, Redeker NS, Knauert MP
    Comput Methods Programs Biomed, 2021 Sep, 209: 106292
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  20. Development and Validation of a Risk Prediction Model for 1-Year Readmission Among Young Adults Hospitalized for Acute Myocardial Infarction.
    Dreyer RP, Raparelli V, Tsang SW, D'Onofrio G, Lorenze N, Xie CF, Geda M, Pilote L, Murphy TE
    J Am Heart Assoc, 2021 Sep 21, 10(18): e021047
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  21. A case study of ascertainment bias for the primary outcome in the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial.
    Esserman DA, Gill TM, Miller ME, Greene EJ, Dziura JD, Travison TG, Meng C, Peduzzi PN
    Clin Trials, 2021 Apr, 18(2): 207-214
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  22. A New Tool to Assess Clinician Experience With Patient Care Transitions.
    Fekieta R, Rosenberg A, Jenq GY, Emerson BL
    Qual Manag Health Care, 2021 Apr-Jun 01, 30(2): 87-96
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  23. Cognitively Impaired Older Persons' and Caregivers' Perspectives on Dementia-Specific Advance Care Planning.
    Fried TR, Cohen AB, Harris JE, Moreines L
    J Am Geriatr Soc, 2021 Apr, 69(4): 932-937
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    Citations: 7 | AltScore: 5.85
  24. Effect of the STAMP (Sharing and Talking About My Preferences) Intervention on Completing Multiple Advance Care Planning Activities in Ambulatory Care : A Cluster Randomized Controlled Trial.
    Fried TR, Paiva AL, Redding CA, Iannone L, O'Leary JR, Zenoni M, Risi MM, Mejnartowicz S, Rossi JS
    Ann Intern Med, 2021 Nov, 174(11): 1519-1527
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  25. THE USES AND ABUSES OF AN AGE-PERIOD-COHORT METHOD: ON THE LINEAR ALGEBRA AND STATISTICAL PROPERTIES OF INTRINSIC AND RELATED ESTIMATORS.
    Fu Q, Guo X, Jeon SY, Reither EN, Zang E, Land KC
    Math Found Comput, 2021 Feb, 4(1): 45-59
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  26. Lung-Protective Ventilation Over 6 Years at a Large Academic Medical Center: An Evaluation of Trends, Adherence, and Perceptions of Benefit.
    Gao CA, Howard FM, Siner JM, Candido TD, Ferrante LE
    Crit Care Explor, 2021 Jan, 3(1): e0325
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  27. Geriatric conditions and treatment burden following diagnosis of non-muscle- invasive bladder Cancer in older adults: A population-based analysis.
    Garg T, Johns A, Young AJ, Nielsen ME, Tan HJ, McMullen CK, Kirchner HL, Cohen HJ, Murphy TE
    J Geriatr Oncol, 2021 May 7, 12(7): 1022-1030
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  28. A Longitudinal Analysis of Functional Disability, Recovery, and Nursing Home Utilization After Hospitalization for Ambulatory Care Sensitive Conditions Among Community-Living Older Persons.
    Gettel CJ, Venkatesh AK, Leo-Summers LS, Murphy TE, Gahbauer EA, Hwang U, Gill TM
    J Hosp Med, 2021 Aug, 16(8): 469-475
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  29. Setting realistic expectations for an innovative program of home-based care for vulnerable older persons.
    Gill TM
    J Am Geriatr Soc, 2021 Dec, 69(12): 3413-3415
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  30. Trends in Restricting Symptoms at the End of Life from 1998 to 2019: A Cohort Study of Older Persons.
    Gill TM, Gahbauer EA, Leo-Summers L, Murphy TE
    J Am Geriatr Soc, 2021 Feb, 69(2): 450-458
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  31. Functional Effects of Intervening Illnesses and Injuries After Hospitalization for Major Surgery in Community-living Older Persons.
    Gill TM, Han L, Gahbauer EA, Leo-Summers L, Murphy TE, Becher RD
    Ann Surg, 2021 May 1, 273(5): 834-841
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  32. Functional Effects of Intervening Illnesses and Injuries After Critical Illness in Older Persons.
    Gill TM, Han L, Gahbauer EA, Leo-Summers L, Murphy TE, Ferrante LE
    Crit Care Med, 2021 Jun 1, 49(6): 956-966
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  33. Falls in older adults after hospitalization for acute myocardial infarction.
    Goldstein DW, Hajduk AM, Song X, Tsang S, Geda M, McClurken JB, Tinetti ME, Krumholz HM, Chaudhry SI
    J Am Geriatr Soc, 2021 Dec, 69(12): 3476-3485
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  34. Defining the Neuropathological Aggresome across in Silico, in Vitro, and ex Vivo Experiments.
    Gomes GN, Levine ZA
    J Phys Chem B, 2021 Mar 4, 125(8): 1974-1996
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  35. Presentation, Treatment, and Outcomes of the Oldest-Old Patients with Acute Myocardial Infarction: The SILVER-AMI Study.
    Gupta A, Tsang S, Hajduk A, Krumholz HM, Nanna MG, Green P, Dodson JA, Chaudhry SI
    Am J Med, 2021 Jan, 134(1): 95-103
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  36. The coronal plane maximum diameter of deep intracerebral hemorrhage predicts functional outcome more accurately than hematoma volume.
    Haider SP, Qureshi AI, Jain A, Tharmaseelan H, Berson ER, Majidi S, Filippi CG, Mak A, Werring DJ, Acosta JN, Malhotra A, Kim JA, Sansing LH, Falcone GJ, Sheth KN, Payabvash S
    Int J Stroke, 2021 Oct 13 17474930211050749
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  37. Admission computed tomography radiomic signatures outperform hematoma volume in predicting baseline clinical severity and functional outcome in the ATACH-2 trial intracerebral hemorrhage population.
    Haider SP, Qureshi AI, Jain A, Tharmaseelan H, Berson ER, Zeevi T, Majidi S, Filippi CG, Iseke S, Gross M, Acosta JN, Malhotra A, Kim JA, Sansing LH, Falcone GJ, Sheth KN, Payabvash S
    Eur J Neurol, 2021 Sep, 28(9): 2989-3000
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  38. Presentation, Treatment, and Outcomes of Older Adults Hospitalized for Acute Myocardial Infarction According to Cognitive Status: The SILVER-AMI Study.
    Hajduk AM, Saczynski JS, Tsang S, Geda ME, Dodson JA, Ouellet GM, Goldberg RJ, Chaudhry SI
    Am J Med, 2021 Jul, 134(7): 910-917
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  39. Pain, Complex Chronic Conditions and Potential Inappropriate Medication in People with Dementia. Lessons Learnt for Pain Treatment Plans Utilizing Data from the Veteran Health Administration.
    Husebo BS, Kerns RD, Han L, Skanderson M, Gnjidic D, Allore HG
    Brain Sci, 2021 Jan 11, 11(1):
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  40. Emergency department visits for emergent conditions among older adults during the COVID-19 pandemic.
    Janke AT, Jain S, Hwang U, Rosenberg M, Biese K, Schneider S, Goyal P, Venkatesh AK
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  41. Utility of a short, telephone-administered version of the Montreal Cognitive Assessment.
    Jennings LA, Araujo KLB, Meng C, Peduzzi P, Charpentier P, Reuben DB
    J Am Geriatr Soc, 2021 Jun 9, 69(10): 2741-2744
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  42. Statin treatment and cerebral microbleeds: A systematic review and meta-analysis.
    Katsanos AH, Lioutas VA, Charidimou A, Catanese L, Ng KKH, Perera K, de Sa Boasquevisque D, Falcone GJ, Sheth KN, Romero JR, Tsivgoulis G, Smith EE, Sharma M, Selim MH, Shoamanesh A, International META-MICROBLEEDS Initiative.
    J Neurol Sci, 2021 Jan 15, 420: 117224
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  43. Stroke Disparities Among Nonracial Minorities in the All of Us Research Program.
    Leasure AC, Acosta JN, Both C, Szejko N, Brown SC, Sheth KN, Falcone GJ
    Stroke, 2021 Aug, 52(8): e488-e490
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  44. Association of Serum IL-6 (Interleukin 6) With Functional Outcome After Intracerebral Hemorrhage.
    Leasure AC, Kuohn LR, Vanent KN, Bevers MB, Kimberly WT, Steiner T, Mayer SA, Matouk CC, Sansing LH, Falcone GJ, Sheth KN
    Stroke, 2021 May, 52(5): 1733-1740
    https://doi.org/10.1161/STROKEAHA.120.032888 | PMID: 33682454 | PMCID: PMC8085132
    Citations: 1 | AltScore: 30.95
  45. Adverse childhood circumstances and cognitive function in middle-aged and older Chinese adults: Lower level or faster decline?
    Lin Z, Chen X
    SSM Popul Health, 2021 Jun, 14: 100767
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  46. Association between emergency department chief complaint and adverse hospitalization outcomes: A simple early warning system?
    Lord K, Rothenberg C, Parwani V, Finn E, Khan A, Sather J, Ulrich A, Chaudhry S, Venkatesh A
    Am J Emerg Med, 2021 Jul, 45: 548-550
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  47. Telecommuting and gender inequalities in parents' paid and unpaid work before and during the COVID-19 pandemic.
    Lyttelton T, Zang E, Musick K
    J Marriage Fam, 2021 Nov 10, 84(1): 230-249
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  48. Mechanisms of Hypoxia-Induced Pulmonary Arterial Stiffening in Mice Revealed by a Functional Genetics Assay of Structural, Functional, and Transcriptomic Data.
    Manning EP, Ramachandra AB, Schupp JC, Cavinato C, Raredon MSB, B?rnthaler T, Cosme C Jr, Singh I, Tellides G, Kaminski N, Humphrey JD
    Front Physiol, 2021, 12: 726253
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  49. Individual Heterogeneity in the Probability of Hospitalization, Skilled Nursing Facility Admission, and Mortality.
    McAvay GJ, Vander Wyk B, Allore H
    J Gerontol A Biol Sci Med Sci, 2021 Aug 13, 76(9): 1668-1677
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  50. Spousal Influences on Monthly Disability in Late-Life Marriage in the Precipitating Events Project.
    Monin JK, Laws H, Gahbauer E, Murphy TE, Gill TM
    J Gerontol B Psychol Sci Soc Sci, 2021 Jan 18, 76(2): 283-288
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  51. Changes in Functional Status and Health-Related Quality of Life in Older Adults After Surgical, Interventional, or Medical Management of Acute Myocardial Infarction.
    Mori M, Djulbegovic M, Hajduk AM, Holland ML, Krumholz HM, Chaudhry SI
    Semin Thorac Cardiovasc Surg, 2021 Spring, 33(1): 72-81
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  52. Diffusion-Weighted Imaging Lesions After Intracerebral Hemorrhage and Risk of Stroke: A MISTIE III and ATACH-2 Analysis.
    Murthy SB, Zhang C, Gupta A, Cho SM, Rivera-Lara L, Avadhani R, Gruber J, Iadecola C, Falcone GJ, Sheth KN, Qureshi AI, Goldstein JN, Hanley DF, Kamel H, Ziai WC
    Stroke, 2021 Jan, 52(2): 595-602
    https://doi.org/10.1161/STROKEAHA.120.031628 | PMID: 33467877 | PMCID: PMC8340082
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  53. Contemporary National Patterns of Eligibility and Use of Novel Cardioprotective Antihyperglycemic Agents in Type 2 Diabetes Mellitus.
    Nargesi AA, Jeyashanmugaraja GP, Desai N, Lipska K, Krumholz H, Khera R
    J Am Heart Assoc, 2021 Jul 6, 10(13): e021084
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  54. Prevalence, Correlates, and Treatment of Suicidal Behavior in US Military Veterans: Results From the 2019-2020 National Health and Resilience in Veterans Study.
    Nichter B, Stein MB, Norman SB, Hill ML, Straus E, Haller M, Pietrzak RH
    J Clin Psychiatry, 2021 Aug 10, 82(5):
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  55. MicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease.
    Nouws J, Wan F, Finnemore E, Roque W, Kim SJ, Bazan I, Li CX, Skold CM, Dai Q, Yan X, Chioccioli M, Neumeister V, Britto CJ, Sweasy J, Bindra R, Wheelock ?M, Gomez JL, Kaminski N, Lee PJ, Sauler M
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  56. Anticoagulant Use for Atrial Fibrillation Among Persons With Advanced Dementia at the End of Life.
    Ouellet GM, Fried TR, Gilstrap LG, O'Leary JR, Austin AM, Skinner JS, Cohen AB
    JAMA Intern Med, 2021 Aug 1, 181(8): 1121-1123
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  57. Functional Disability Among Older Versus Younger Adults With Advanced Non-Small-Cell Lung Cancer.
    Presley CJ, Arrato NA, Janse S, Shields PG, Carbone DP, Wong ML, Han L, Gill TM, Allore HG, Andersen BL
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  58. Prevalence of Memory-Related Diagnoses Among U.S. Older Adults With Early Symptoms of Cognitive Impairment.
    Qian Y, Chen X, Tang D, Kelley AS, Li J
    J Gerontol A Biol Sci Med Sci, 2021 Sep 13, 76(10): 1846-1853
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  59. Racial and Ethnic Differences in Multimorbidity Changes Over Time.
    Qui?ones AR, Newsom JT, Elman MR, Markwardt S, Nagel CL, Dorr DA, Allore HG, Botoseneanu A
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  60. Barriers to implementation of STRIDE, a national study to prevent fall-related injuries.
    Reckrey JM, Gazarian P, Reuben DB, Latham NK, McMahon SK, Siu AL, Ko FC
    J Am Geriatr Soc, 2021 Feb 13, 69(5): 1334-1342
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  61. Medicare Beneficiaries With Self-Reported Functional Hearing Difficulty Have Unmet Health Care Needs.
    Reed NS, Assi L, Horiuchi W, Hoover-Fong JE, Lin FR, Ferrante LE, Inouye SK, Miller Iii ER, Boss EF, Oh ES, Willink A
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  62. A Multimodal Intervention to Improve the Quality and Safety of Interhospital Care Transitions for Nontraumatic Intracerebral and Subarachnoid Hemorrhage.
    Sather J, Littauer R, Finn E, Matouk C, Sheth K, Parwani V, Pham L, Ulrich A, Rothenberg C, Venkatesh AK
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  63. Trajectories of Late-Life Disability Vary by the Condition Leading to Death.
    Stolz E, Gill TM, Mayerl H, R?sky ?, Freidl W
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  64. Genetic determinants of LDL cholesterol and risk of intracerebral haemorrhage.
    Szejko N, Kirsch E, Falcone GJ
    Curr Opin Lipidol, 2021 Aug 1, 32(4): 244-248
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  65. Prognosis as Health Trajectory: Educating Patients and Informing the Plan of Care.
    Thomas JM, Cooney LM Jr, Fried TR
    J Gen Intern Med, 2021 Jul, 36(7): 2125-2126
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  66. Outcome Goals and Health Care Preferences of Older Adults With Multiple Chronic Conditions.
    Tinetti ME, Costello DM, Naik AD, Davenport C, Hernandez-Bigos K, Van Liew JR, Esterson J, Kiwak E, Dindo L
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  67. Demographic Characteristics Driving Disparities in Receipt of Long-term Services and Supports in the Community Setting.
    Travers JL, Naylor MD, Coe NB, Meng C, Li F, Cohen AB
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  68. Engagement in Non-Medical End-of-Life Planning by Older Adults.
    Tu SS, O'Leary JR, Fried TR
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  69. Trajectories of Cognitive and Motor Function Between Ages 45 and 90 Years: A Population-Based Study.
    van der Willik KD, Licher S, Vinke EJ, Knol MJ, Darweesh SKL, van der Geest JN, Schagen SB, Ikram MK, Luik AI, Ikram MA
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  70. Prognostic information, goals of care, and code status decision-making among older patients.
    van Dyck LI, Fried TR
    J Am Geriatr Soc, 2021 Jul, 69(7): 2025-2028
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  71. Understanding the Role of Knowledge in Advance Care Planning Engagement.
    van Dyck LI, Paiva A, Redding CA, Fried TR
    J Pain Symptom Manage, 2021 Oct, 62(4): 778-784
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  72. Brief Report: Are Serious Falls Associated With Subsequent Fragility Fractures Among Veterans Living With HIV?
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  73. Polypharmacy Results in Functional Impairment in Mice: Novel Insights Into Age and Sex Interactions.
    Wu H, Mach J, Gemikonakli G, Tran T, Allore H, Gnjidic D, Howlett SE, de Cabo R, Le Couteur DG, Hilmer SN
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  74. Assessing elderly's functional balance and mobility via analyzing data from waist-mounted tri-axial wearable accelerometers in timed up and go tests.
    Yu L, Zhao Y, Wang H, Sun TL, Murphy TE, Tsui KL
    BMC Med Inform Decis Mak, 2021 Mar 25, 21(1): 108
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  75. Intergenerational upward mobility and racial differences in mortality among young adults: Evidence from county-level analyses.
    Zang E, Kim N
    Health Place, 2021 Jul, 70: 102628
    https://doi.org/10.1016/j.healthplace.2021.102628 | PMID: 34280713 | PMCID: PMC8328956
    Citations: 3 | AltScore: 38.78
  76. Regional differences in the impact of diabetes on population health in the USA.
    Zang E, Lynch SM, West J
    J Epidemiol Community Health, 2021 Jan, 75(1): 56-61
    https://doi.org/10.1136/jech-2020-214267 | PMID: 32855262 | PMCID: PMC8128513
    Citations: 2 | AltScore: 28.998
  77. U.S. regional differences in physical distancing: Evaluating racial and socioeconomic divides during the COVID-19 pandemic.
    Zang E, West J, Kim N, Pao C
    PLoS One, 2021, 16(11): e0259665
    https://doi.org/10.1371/journal.pone.0259665 | PMID: 34847174 | PMCID: PMC8631641
    Citations: 2 | AltScore: 39.45
  78. Modeling SARS-CoV-2 propagation using rat coronavirus-associated shedding and transmission.
    Zeiss CJ, Asher JL, Vander Wyk B, Allore HG, Compton SR
    PLoS One, 2021, 16(11): e0260038
    https://doi.org/10.1371/journal.pone.0260038 | PMID: 34813610 | PMCID: PMC8610237
    Citations: 1 | AltScore: 0.75
  79. SUPERGNOVA: local genetic correlation analysis reveals heterogeneous etiologic sharing of complex traits.
    Zhang Y, Lu Q, Ye Y, Huang K, Liu W, Wu Y, Zhong X, Li B, Yu Z, Travers BG, Werling DM, Li JJ, Zhao H
    Genome Biol, 2021 Sep 7, 22(1): 262
    https://doi.org/10.1186/s13059-021-02478-w | PMID: 34493297 | PMCID: PMC8422619
    Citations: 7 | AltScore: 15.88


EXTERNAL ADVISORY BOARD MEMBERS

Ana Maria Cuervo, M.D., Ph.D
Albert Einstein College of Medicine
Serving since 2012 (10 years)

Edward Marcantonio, MD, SM
Beth Israel Deaconess Medical Center
Serving since 2012 (10 years)

Heather Whitson, MD
Duke University School of Medicine & Durham VA Medical Center
Serving since 2016 (6 years)

Neil Alexander, M.D., M.S.
University of Michigan
Serving since 2016 (6 years)


RECOGNITION AND AWARDS (2021-2022)
Edward Manning (2021)
  • Butler-Williams Scholar: National Institute on Aging: Butler Williams Scholar
Lauren Ferrante (2021)
  • Outstanding Junior Investigator of the Year Award, American Geriatrics Society (AGS)
Lauren Ferrante (2022)
  • American Society for Clinical Investigation (ASCI) Young Physician-Scientist Award, 2022
Morgan Levine (2021)
  • Vincent Cristofalo Rising Star Award in Aging Research

MINORITY RESEARCH

General Brief Description of Minority Activities:
Not defined.


Minority Trainee(s):
  • Lauren Ferrante, Assistant Professor of Medicine (Pulmonary); Director, Operations Core, Yale Claude D. Pepper Older Americans Independence Center
    Lauren Ferrante, MD, MHS, assistant professor of medicine (pulmonary, critical care, & sleep medicine), is the Director of the Operations Core and serves as a member of the Yale OAIC Executive Committee, which meets bimonthly.

Minority Grant(s):