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 (BDAC)
Leader 1:    Terrence E. Murphy, PhD   terrence.murphy@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
 
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)
 
Brienne Miner
Assistant Professor of Medicine (Geriatrics) / Yale University
Insomnia Symptoms as a Multifactorial Geriatric Health Condition
2019-2021 /
4 (total)
2 (1st/Sr)
 
Maor Sauler
Assistant Professor of Medicine (Pulmonary) / Yale University
Assessing Multiple Pathways of DNA Damage Responses in Normal Lung Aging and in Chronic Obstructive Pulmonary Disease (COPD)
2019-2021 /
1 (total)
0 (1st/Sr)
 

Past Scholars
Xi Chen, Yale University (2016-2020)
Guido Falcone, Yale University (2017-2020)
Janice Hwang, Yale University (2018-2020)
Morgan Levine, Yale University (2018-2020)
Joan Monin, Yale University (2018-2020)

PILOT/EXPLORATORY PROJECTS (7 Pilot Projects Listed)
1. Project Title: Assessing Multiple Pathways of DNA Damage Responses in Normal Lung Aging and in Chronic Obstructive Pulmonary Disease (COPD): REC (2019-2021)
  Leader: Maor Sauler
  The aging lung is characterized by a physiologic decline in lung function and increased susceptibility to disease. Many parallels have been identified between normal lung aging and the leading cause of respiratory disease amongst older adults, Chronic Obstructive Pulmonary Disease (COPD). Although advanced age and cigarette smoke exposure are leading COPD risk factors, not all at-risk individuals develop disease, and the pathologic and clinical manifestations amongst susceptible individuals vary widely. This is because COPD is a multifactorial syndrome in which multiple poorly understood cellular and molecular interactions contribute to disease susceptibility and pathobiology. Our goal is to translate advances in aging biology into a better understanding of the cellular and molecular interactions that underlie differences between normal lung aging and COPD in order to develop more effective approaches to diagnose, prevent, and treat this disease of the elderly. DNA damage responses are important in the biology of aging and COPD. DNA damage occurs in all cells with age, a process that is accelerated by cigarette smoke. In response to DNA damage, cells can activate multiple DNA damage responses (DDRs). Certain DDRs are protective such as DNA repair pathways. Others are implicated in COPD pathogenesis, such as cell senescence and apoptosis. We do not fully understand how the cellular capacity for DNA repair changes in COPD, or if COPD airway cells are more likely to activate certain deleterious DDRs in response to injury. We hypothesize that we can identify critical differences between normal lung aging and COPD by characterizing multiple DDRs in epithelial cells using novel molecular approaches. Understanding similarities in DDRs between normal lung aging and COPD may improve our ability to understand disease heterogeneity. Additionally, it may lead to the identification of novel DDR regulatory factors that contribute to disease susceptibility
 
2. Project Title: Insomnia Symptoms as a Multifactorial Geriatric Health Condition: REC (2019-2021)
  Leader: Brienne Miner
  Insomnia symptoms are reported by up to 50% of persons aged 65 and older. These symptoms, which include difficulties with sleep onset or maintenance, early morning awakening, or perceived non-restorative sleep, are associated with multiple adverse outcomes including cognitive decline, depression, falls, and high healthcare costs. The traditional treatment approach for insomnia symptoms targets primary sleep disorders (obstructive sleep apnea, restless legs syndrome or periodic limb movement disorder), and/or cognitive behavioral therapy for insomnia, but the effectiveness of these strategies may be limited because of the multifactorial etiology of insomnia symptoms in older persons. Understanding how aging-related, “gerocentric” risk factors contribute, above and beyond primary sleep disorders, to insomnia may yield a more comprehensive approach and allow us to tailor treatments specifically to older persons. Gerocentric factors (e.g., multimorbidity, symptom burden, medication effects, geriatric health conditions [e.g., cognitive or vision impairments], physical inactivity, psychosocial/behavioral factors, and systemic inflammation) may disrupt sleep through multiple mechanisms. These factors are prevalent and potentially modifiable. In addition, many gerocentric factors may occur simultaneously within the same person, and determining how these factors cluster together within older persons has the potential to impact both the diagnosis and treatment of insomnia. Insomnia diagnosis in older persons may be better evaluated by measures that incorporate both patient reported symptoms and short total sleep time (TST). Insomnia diagnosis is traditionally based on patient reported insomnia symptoms and daytime dysfunction, which are elements captured by the Pittsburgh Sleep Quality Index (PSQI). However, a growing body of research has shown the importance of evaluating short TST, as persons with both insomnia symptoms and short TST may represent a group at high risk for adverse outcomes. Thus, we propose a new definition for insomnia that is based on both PSQI-measured poor sleep quality and short TST. We further propose that TST should be defined objectively using actigraphy. This is supported by evidence of a poor correlation between subjective and objective measures of TST in older persons, as well as research demonstrating that older persons may be less likely to report or perceive the severity of symptoms in the setting of objective disease. As a result, actigraphy-confirmed insomnia (poor sleep quality and actigraphy-confirmed short TST) rather than patient-reported insomnia (poor sleep quality and self-reported short TST) may better assess insomnia severity in older persons. This research will bring an aging perspective to the management of insomnia by evaluating a new diagnostic approach that incorporates the contribution of gerocentric risk factors. In particular, we will identify aging-related mechanisms underlying insomnia, thus informing its immediate management, and quantify the risk of adverse health outcomes, informing the need for proactive, preventive interventions. This work will inform a future K award application targeted toward vulnerable older adults with cognitive impairment, building a multifactorial intervention for insomnia based on modifiable risk factors and an improved diagnostic strategy. Our results may inform multifactorial treatment strategies that will have broad benefits in older persons.
 
3. Project Title: What Matters in the ED: older adults’ desires and providers’ beliefs: Small REC (2019-2020)
  Leader: Cameron Gettel
  The overall objective of this proposal is to identify the fears, concerns, and desired outcomes of older adults regarding their healthcare in the ED, and descriptively understand if ED providers are prioritizing patient-centered outcomes during their care. The proposed investigation adheres to the Pepper Center theme of investigating multifactorial geriatric health conditions by embracing methods of multiple chronic conditions research. A key feature of multiple chronic conditions research is attention to multilevel contextual factors that impact patient outcomes. In the brief interviews, patient fears and desired outcomes will elicit the predisposing factors (physiologic, impairment, disease, sociodemographic) and precipitating factors (behavioral, environmental, social, medical, psychological) for seeking care. By assessing underlying comorbidities, the proposed investigation will integrate multilevel contextual factors and provide meaningful baseline descriptive information on the level to which patient priorities and desired outcomes are being addressed in the ED. Through the use of interviews aimed at identifying patient-centered clinical outcomes, the proposed investigation recognizes some of the many factors that impact health in older persons. Furthermore, assessment of ED providers’ priorities and their interpretation of what outcomes they believe patients prefer will advance clinical decision-making, particularly identifying older person’s health outcome priorities.
 
4. Project Title: Leveraging Machine Learning Methods and Life Course Approach to Understand Dementia Risk and Its Racial/Ethnic Disparities (PESC: 2020- 2021)
  Leader: Xi Chen
  There are marked differences in rates of dementia among US older adults, the fastestgrowing segment of the population. For example, the prevalence rate of dementia for non- Hispanic Blacks (Blacks) and Hispanics are much higher than that of non-Hispanic Whites (Whites), after accounting for age, sex, education, and late-life comorbidities. Despite growing evidence of racial disparities in cognitive health and dementia risk, specific life course causes remain largely unclear and underexplored. The extent to which these differences exacerbate or mitigate dementia risk and its racial/ethnic disparities is unknown. Latest studies suggest that the root of dementia risk may be traced back to early life, and interventions can be most successful if applied early in life, prior to the onset of dementia. The rising share of U.S older population who are Hispanics or Blacks may lead to a considerable rise in socioeconomic burden associated with dementia, making it imperative to improve our understanding of these issues. We utilize a nationally representative Health and Retirement Study (HRS) sample of over 10,000 Black, Hispanic and White individuals age 65 and older, who are linked to extremely rich information during their childhood and adulthood collected by the HRS Life History Survey. Dementia is identified using a validated method based on a probability model developed using a sub-study of HRS, the Aging, Demographics, and Memory Study (ADAMS), that assigned dementia diagnosis among a subsample of HRS respondents via a comprehensive in-home clinical and neuropsychological assessment to determine a diagnosis of normal, cognitively impaired without dementia (CIND), or dementia. Therefore, rich multi-factorial life course factors at the individual level, the family level, and the community level and the reliable assessment of the whole spectrum of dementia risk provide us ideal database for this pilot/exploratory study. This study aims to explore machine learning (ML) methods to deepen our understanding of life course determinants of dementia risk and racial/ethnic disparities and select most appropriate models for dementia risk prediction for older Americans. ML has demonstrated enormous potential for early detection of diseases and lowering costs. The applications of ML to prediction models circumvents key statistical problems that plague the literature, including arbitrary selection of variables/models, overfitting, insufficient use of information in the data. ML methods enable us to identify models with greatly improved out-of-sample prediction accuracy. We identify key modifiable life course factors that contribute to dementia risk and its racial/ethnic differences, including early life and mid-life circumstances and behavior and lifestyle choices, focusing in particular on factors that may be modifiable. These findings will inform development of well-targeted interventions prior to the onset of dementia, both preventive and service-driven, to slow the process of cognitive impairment and help narrow and address dementia-related disparities across racial/ethnic groups.
 
5. Project Title: Feasibility, Acceptability, and Barriers to Implementation of a Geriatrics Bundle in the ICU: a Pilot Study: PESC (2020-2021)
  Leader: Lauren Ferrante
  Millions of older adults are admitted to an intensive care unit (ICU) every year, and most will present with one or more preexisting vulnerability factors (e.g. frailty or sensory impairment) that increase the likelihood of adverse outcomes, such as delirium and functional decline. The critical illness itself, coupled with insults from the ICU environment (e.g. immobility and polypharmacy), culminate in a “perfect storm” that makes these adverse outcomes more likely. Despite the known benefits of geriatric care models among hospitalized older adults outside the ICU, few studies have addressed the needs of older adults in the ICU; for example, sensory impairment, functional decline, and deprescribing of potentially inappropriate medications (PIMs) are rarely addressed in routine ICU practice. Before the effectiveness of these interventions can be evaluated in a largescale study, however, it is essential to evaluate the feasibility, acceptability, and barriers and facilitators to implementing these interventions in the fast-paced ICU setting. In considering the best method of effecting change in the ICU, it is helpful to consider what implementation strategies have been most effective in the past. Without question, high-quality ICU practices have been most effectively implemented through the use of bundles and checklists. The ABCDEF bundle, which incorporates several evidence-based components, is widely considered the standard for modern-day quality ICU practice. The ABCDEF bundle components are (A)ssess/manage pain, (B)oth spontaneous awakening and spontaneous breathing trials, (C)hoice of analgesia/sedation, (D)elirium assessment, prevention, and management, (E)arly Mobilization, and (F)amily engagement. Checklists, which are used daily on rounds on every patient in ICUs across the country, complement the use of ICU bundles by providing helpful “nudges” for the individual bundle components. We have developed a geriatrics bundle for the ICU that complements the existing ABCDEF bundle while incorporating evidence-based interventions from geriatric models of care. By delivering these interventions as a bundle, and reinforcing the individual components using the ICU checklist, we are leveraging strategies that have demonstrated success in the ICU setting. The geriatrics bundle includes 3 components: occupational therapy to deliver function-focused rehabilitation (in addition to mobilization delivered by physical therapy), the assessment and treatment of hearing impairment, and a routine deprescribing intervention upon ICU-to-floor transfer to eliminate PIMs initiated in the ICU. The bundle components are supported by evidence in hospitalized older adults: occupational therapy (Component 1) improves function in activities of daily living (ADLs), with early studies supporting its use in the ICU; the treatment of hearing impairment (Component 2) reduces incident delirium and improves functional outcomes; and deprescribing of PIMs initiated in the ICU upon ICU-to-floor transfer (Component 3) helps reduce inappropriate prescribing and polypharmacy. The overall objective of this proposal is to evaluate the feasibility, acceptability, and barriers to implementation of the geriatrics bundle in the ICU. This pilot work will provide invaluable preliminary data for a future hybrid effectiveness-implementation study of the geriatrics bundle in the ICU, with a long-term goal of adding the geriatrics bundle as the “G” component of the ABCDEF bundle to facilitate widespread implementation.
 
6. 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.

 
7. 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.
 
DEVELOPMENT PROJECTS (2 Development Projects Listed)
1. Project Title: Quality of Life Among Older Spousal Dementia Caregivers: A Multifactorial Approach (2020-2021)
  Leader: Emma Zang
  Core(s):
  Emma Zang, PhD, Assistant Professor (Sociology) was provided with a joint Biostatistics-REC small award to apply sophisticated Bayesian trajectory modeling and multi-state life tables techniques in order to understand longitudinal patterns in the health of older persons with dementia and their caregivers. The structure of Dr. Zang’s position as a member of the Faculty of Arts and Sciences was not a good fit with the Pepper Scholar funding mechanism. The small REC funding has allowed Dr. Zang to develop collaborative relationships with members of the Pepper Center, which has culminated in the submission of an R03 that is currently under consideration for funding.
 
2. Project Title: “Expanding the capacity for OAIC digital phenotyping using Real-time, Online Assessment and Mobility Monitoring (ROAMM) of falls in older adults" (2020-2021)
  Leader: Alexandra Hajduk
  Core(s):
  Dr. Hajduk is obtaining qualitative accounts from enrolled participants to understand the perceived benefits, facilitators, and barriers on the data collection components of the ROAMM platform. At the end of the data collection period for the parent project, a short semi-structured interview consisting of open-ended questions regarding ROAMM. Dr. Hajduk is obtaining qualitative accounts from enrolled participants to understand the perceived benefits, facilitators, and barriers on the data collection components of the ROAMM platform. Interviews are being conducted in a convenience sample of consecutively enrolled participants until thematic saturation is reached, with a final projected sample size of 20 to 25 participants. We are obtaining perspectives of participants of different ages, sexes, education levels, and functional levels. All 11 participants who completed the quantitative ROAMM study at Yale also participated in the qualitative study funded by the Development Project. Participants were asked open-ended questions about comfort, usability, and acceptability of the Smartwatch and ROAMM application.
 
RESEARCH (20 Projects Listed)
1. Project Title: PROMOTING ADVANCE CARE PLANNING AS A HEALTHY BEHAVIOR
  Leader(s): FRIED, TERRI R.
    VA CONNECTICUT HEALTHCARE SYSTEM
    VA I01HX002062 / ( 2017 - 2021 )
  Core(s):
  The recent Institute of Medicine report Dying in America: Improving Quality and Honoring IndividualPreferences near the End of Life endorses advance care planning (ACP) as a key component of qualityhealthcare. In contrast to the prevailing model of engaging only individuals with serious illness in ACP, itproposes a continuous process, starting earlier in the lifespan with individuals in good health. Such anapproach helps to prepare the individual for more in-depth discussions and treatment decision making as moreserious illness develops. This project is responsive to this call. It builds upon earlier work of the PrincipalInvestigator (PI) providing two key insights for improving the process of ACP. The first of these is shifting thepurpose of ACP away from the pre-specification of treatment preferences to preparation for making the bestpossible in-the-moment healthcare decisions. This is accomplished by conceptualizing ACP as acts ofcommunication among patients, surrogates, and clinicians. The second is explicitly addressing the manyattitudinal, cognitive, and behavioral barriers to engagement in ACP. This is accomplished by treating ACP asa health behavior and intervening using validated models for health behavior change. The PI has developedand pilot-tested an intervention based on the Trans-Theoretical Model. This intervention consists of an expertsystem that assesses an individual's readiness to engage in ACP along with the attitudes and beliefsinfluencing the desire, motivation, and ability to engage. It then provides individually tailored feedbackmaterials providing information, motivation, and/or behavior change strategies (computer-tailored informationor CTI). This project will also utilize a form of motivational interviewing called motivational enhancementtherapy (MET), which, while also including the concept of readiness for behavior change, is distinct from CTI. Itconsists of brief counseling exploring an individual's readiness to engage in behavior change and helping theindividual to identify motivators for change. The objective of the project is to examine the effects of CTI and MET on Veteran engagement in ACP. Thespecific aim is: To conduct a randomized controlled trial examining the effects of: a) usual care; b) CTI; c)MET; d) CTI + MET on the proportion of middle-age and older Veterans receiving primary care at the VA whocomplete the process of ACP. Broad eligibility criteria will be used to identify Veterans age 55 years and olderwho are receiving primary care within VA Connecticut Healthcare System and who have not completed all ofthe 4 key ACP behaviors: health care proxy assignment, living will completion, communication with the healthcare proxy about views on quality vs. quantity of life, communication with the clinician about these views. Theintervention(s) will be delivered over the phone. For Veterans receiving CTI, an individually tailored feedbackreport, a stage-matched brochure, and a pamphlet for the surrogate will be mailed. This will be repeated at 2and 4 months. For Veterans receiving MI, the Veteran and surrogate will participate in a dyadic interview.Follow-up interviews will occur at 2 and 4 months. For Veterans receiving CTI + MI, the printed materials willbe mailed, and the interview will be conducted within 2 weeks. Baseline measures, including stage of changefor the 4 key ACP behaviors, pros and cons of behavior change, and health status and sociodemographicvariables, will be obtained for all participants. The outcome measure, obtained at 6 months, will be theproportion of participants who have completed the 4 ACP behaviors. The proposal will also lay the groundworkfor more widespread implementation by collecting implementation data on the time and effort required todeliver the interventions, success of and barriers to delivering the interventions, and spill-over effects on otherclinical services. Additional work will be done to strategize about the most efficient ways to embed theinterventions into existing clinical services.
 
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: EPIDEMIOLOGY OF DISABILITY AND RECOVERY IN OLDER PERSONS
  Leader(s): GILL, THOMAS MICHAEL
    YALE UNIVERSITY
    NIH R01AG017560 / ( 2000 - 2021 )
  Core(s):
  DESCRIPTION (provided by applicant): The causes and consequences of disability are of fundamental concern to a US population whose age structure is shifting dramatically. An important impediment to the development of interventions to prevent disability and restore independent function has been an incomplete understanding of the disabling process. This application is a competing renewal of an NIA MERIT award, which provides support for the PEP Study, a unique and highly innovative, ongoing study of 754 community-living persons, aged = 70. Over the past 17+ years, participants have completed comprehensive assessments at 18-month intervals and have been interviewed monthly to reassess their functional status and ascertain intervening events, other health care utilization, and deaths. Findings from the PEP Study have greatly enhanced our understanding of the disabling process. To date, 90 original reports have been published, including 76 since the start of the award. Recent linkages with Medicare claims and Connecticut Tumor Registry have further enriched PEP as an unparalleled platform for disability research. Building on our earlier work, this 5-year renewal will rigorouslyevaluate the role of common, but relatively neglected intervening events on the disabling process, investigate the functional antecedents, outcomes, and prognostic determinants of a new cancer diagnosis, elucidate the public health importance of multiple modifiable patient-centered factors on functional outcomes, and determine whether hospice services are being targeted appropriately at the end of life. The Specific Aims are: (1) to identify modifiable factor, from multiple patient-centered domains, that are associated with disability burden and poor functional recovery after a major surgical procedure; (2a) to determine the functional outcomes among older persons who are admitted to an emergency department (ED) but not hospitalized, relative to those who are admitted to an ED and hospitalized and to those who were not admitted to an ED; (2b) to identify modifiable factors, from multiple patient-centered domains, that are associated with poor functional outcomes after an ED admission; (3a) to identify distinct sets of functional trajectories in the year immediately before and after a new cancer diagnosis, evaluate the relationship between the pre- and post-cancer trajectories and determine whether these results differ based on the cancer-specific prognosis; (3b) to identify the patient-centered and cancer-specific factors that are associated with functional decline after a new cancer diagnosis; and (4) among decedents, to evaluate the relationship between the presence and burden of restricting symptoms and disability, respectively, and subsequent enrollment in hospice. This hypothesis-driven research will take advantage of the most comprehensive set of functional data on such a large cohort of older persons, with an excellent participation rate, remarkably low attrition, and little missing data. By further elucidating the epidemiology of disability and recovery, the proposed research will help to inform the development of effective and efficient interventions directed at maintaining and restoring independent function among older persons.
 
6. Project Title: PET IMAGING OF SYNAPTIC DENSITY IN ALZHEIMERS DISEASE
  Leader(s): CARSON, RICHARD E.; VAN DYCK, CHRISTOPHER H ;
    YALE UNIVERSITY
    NIH R01AG052560 / ( 2017 - 2021 )
  Core(s):
  Project Summary/Abstract Alzheimer's disease (AD) afflicts 6 million people in the USA, and the number of AD patients will double by2050 if no cure is identified. The clinical dementia of AD is coupled to a distinct pathology, with -amyloidplaques, neurofibrillary tangles, and synaptic loss. Synapses are essential for cognitive function, and their lossis well established as the major structural correlate of cognitive impairment in AD. An early event in ADpathogenesis, synaptic failure is detectable in individuals with the prodromal stage of MCI. Positron EmissionTomography (PET) imaging is increasingly employed in studies of AD, using tracers for glucose metabolism, -amyloid, and neurofibrillary tangles. However, currently, there are no PET radioligands that directly imagesynaptic density in vivo, which would be of high utility in studies of AD as well as in monitoring potentialtherapies. One suitable molecular target for a synaptic density imaging agent is the synaptic vesicleglycoprotein 2 (SV2), an essential vesicle membrane protein, with one of its isoforms, SV2A, ubiquitouslyexpressed in virtually all synapses. We recently developed 11C-UCB-J as a promising radioligand forquantitative measurement of SV2A with PET. In our pilot first-in-human SV2A PET studies in healthy subjects,we found that 11C-UCB-J has the potential to be an excellent PET tracer for quantitative imaging of SV2A in thehuman brain, and can act as a general-purpose tool for measuring synaptic vesicle density. We propose toapply 11C-UCB-J with human imaging studies in AD. In Aim 1, we will quantify SV2A using bolus/infusiondelivery on the High Resolution Research Tomography (HRRT) and examine SV2A density in AD compared tohealthy controls (HC). We hypothesize that 11C-UCB-J will reveal decreased SV2A binding in the AD brain witha pattern that may differ from the cortical regions previously validated for 18F-FDG. All subjects will also beevaluated for amyloid status and the effect of overall amyloid status on SV2A binding will be determined. InAim 2, we will compare group and individual differences in SV2A density to differences in glucose metabolismmeasured with 18F-FDG. Regional patterns of deficits will be compared to HC for the 2 tracers. We hypothesizethat the magnitude of reduction in specific binding of 11C-UCB-J in AD compared to HC will be greater than thatfound with 18F-FDG. Further, we will correlate the magnitude of reduction in synaptic density and glucosemetabolism with neuropsychological test performance. Aim 3 compares the group and individual differences inamyloid distribution from 11C-PIB to SV2A-PET as well as FDG-PET, with the expectation that patterns ofsynaptic loss produced by 11C-UCB-J will differ from that of amyloid PET, particularly in the earlier phases ofthe AD spectrum. In summary, this project will take the first critical steps to validating a novel imagingbiomarker of synaptic density for studies in AD and other neuropsychiatric disorders.
 
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: THE IMPACT OF HIV INFECTION ON IMMUNOLOGIC, TRANSCRIPTOMIC, AND METABOLOMIC SIGNATURES OF MEDICATION-ASSISTED THERAPY FOR OPIOID ADDICTION
  Leader(s): SPRINGER, SANDRA ANN; SHAW, ALBERT C ;
    YALE UNIVERSITY
    NIH R01DA043337 / ( 2016 - 2021 )
  Core(s):
  The prevalence of HIV infection is 28 to at least 50 times higher among people who inject drugs (PWID)compared to the general population. In North America, there were an estimated 267,000 persons living withHIV infection (PLHs) among 2 million PWIDs in 2012. Opioids represent the dominant class of injected agent,and in 2013 517,000 adults reported heroin use within the past year, representing an approximately 150%increase compared to 2007. Medication-assisted treatment (MAT) for opiate addiction, combined with needleand syringe exchange programs (NESP) have substantially reduced the risk of HIV transmission in PWIDs.Moreover, MAT reduces mortality among HIV-positive PWIDs (which is otherwise 3-fold higher than in PWIDswho are HIV-negative). MAT is predominantly available in the form of opioid agonist treatment with methadoneor buprenorphine, with emerging use of opioid antagonist treatments (e.g. extended-release naltrexone).However, there are no recommendations currently available to guide the selection of MAT agent. Moreover,despite substantial evidence for immunomodulatory effects of opioids on immune responses, to our knowledgeno studies have employed systems biology methods to evaluate MAT agents for their effects on parameterssuch as chronic inflammation particularly important for HIV disease progression and present even in elitecontrollers or individuals who have achieved virologic control without antiretroviral therapy (ART). To addressthese questions, we have assembled an interdisciplinary group of investigators with expertise in HIV disease,the epidemiology of injection drug use and MAT intervention studies for PWID, innate immunity andinflammation, and computational biology. Using methods familiar to our research groups, we will carry out aprospective, longitudinal study of HIV-positive (on ART) vs. HIV-negative PWIDs starting MAT, recruited fromthe largest drug treatment center in New Haven, Connecticut. We will obtain samples of blood at baseline (day0), and at day 3, 14, and at 1, 3, and 6 months after the start of MAT. Freshly collected samples of wholeblood will be analyzed using multidimensional mass cytometry to evaluate the activation and differentiationstate of cells of the innate and adaptive immune system, including novel analyses of platelet activation andfunction as an understudied contributor to chronic inflammation. In addition, we will carry out an unbiasedanalysis of innate immune pattern recognition receptor (PRR) function in monocytes and dendritic cells toassess potential alterations in PRR function that may contribute to dysregulated inflammatory responses.RNA-seq analyses of whole blood, together with metabolomic analyses of serum samples, will also beperformed at these timepoints. We believe the integration of these cellular, immunologic, transcriptomic andmetabolomic signatures will advance the biology of MAT in the context of HIV infection. Moreover, our designof a prospective study and the analysis of freshly isolated cells will facilitate insights that cannot be achievedwith cryopreserved samples and should provide information to guide the selection of MAT agents.
 
13. Project Title: TLR4-MEDIATED EPIGENETIC AND SENESCENCE MECHANISMS IN EMPHYSEMA
  Leader(s): LEE, PATTY J
    DUKE UNIVERSITY
    NIH R01HL138396 / ( 2017 - 2021 )
  Core(s):
  PROJECT SUMMARYCOPD is now the 3rd leading cause of death worldwide. Emphysema, characterized by airspace enlargementand impaired gas exchange, is a major subtype of COPD. The cumulative effects of cigarette smoke exposure(CS) and environmental toxins across the lifespan are important contributing factors to the development ofemphysema. Yet very little is known about the underlying mechanisms, which limits therapies. Our overallgoals are to understand the molecular mechanisms of how our lungs maintain normal structural integrity andhow they protect against inhaled toxins, such as CS. We identified a critical role for an innate immune receptor,Toll-like receptor 4 (TLR4), in lung maintenance and in preventing inappropriate activation of aging and injurypathways. Unfortunately, age and CS, two of the most common risk factors for COPD, result in inadequatelevels of TLR4, thus predisposing to emphysema. Our studies will fill current gaps in our understanding of howthe immune system, in specific lung cells, can impact lung-protective responses even in the absence ofinfection, thereby offering potential new therapeutic targets. Using TLR4-deficiency and CS as clinicallyrelevant experimental models of emphysema, we identified mechanistic roles for the senescence molecule,p16INK4A, and DNA-modifying enzymes, HDAC2, Dnmt3a and Tet2, in emphysema. In addition, we offer thefirst in vivo evidence that increased p16INK4A contributes to emphysema. Our overall hypothesis is thatstructural cell TLR4 is required to maintain normal lung integrity, at baseline and after CS, by inhibitingp16INK4A via HDAC2-Dnmt3a-Tet2-mediated mechanisms. We will use a combination of age- and CS-exposed human and mouse lungs/cells as well as innovative gene manipulations to test this hypothesis in thefollowing Aims: 1) Identify mechanisms of decreased TLR4 expression with aging and CS and thecontribution of TLR4 in specific structural cells to emphysema. 2) Determine the mechanisms of decreasedHDAC2 in TLR4-deficient and CS-exposed cells. 3) Identify HDAC2 and Dnmt3a / Tet2 -mediated mechanismsof p16INK4A induction and the contribution of p16INK4A in specific structural cells to emphysema. Our studies willexpand our basic understanding of the molecular drivers of emphysema, establish previously unrecognizedinteractions amongst innate immunity, senescence and DNA modifications and inform future preventative ortherapeutic approaches to a range of age- and CS-related lung diseases.
 
14. Project Title: UNDERSTANDING DECISIONS ABOUT ANTICOAGULATION IN PATIENTS WITH ATRIAL FIBRILLATION AND DEMENTIA
  Leader(s): OUELLET, GREGORY MICHAEL
    YALE UNIVERSITY
    NIH R03AG064255 / ( 2019 - 2021 )
  Core(s):
  Over 5.5 million Americans over 65 have Alzheimer s Disease (AD) and Alzheimer s Disease-related dementias (ADRD), and many of them have multiple coexisting chronic conditions. Decision-making for chronic conditions often defaults to disease-specific guidelines, which may be inappropriate in the setting of AD/ADRD. Clinical trials often exclude older adults with AD/ADRD, and the benefits and harms of treatments may be quite different than in younger, healthier individuals due to declines in life expectancy, cognition and function. Importantly, guidelines may not address the variable outcomes that patients value most. The decision regarding whether or not to prescribe anticoagulation for a patient with atrial fibrillation is an exemplar of a complex clinical decision often made in the context of coexisting AD/ADRD. Atrial fibrillation is the most common arrhythmia in older adults, and places those affected at significantly increased stroke risk. The current decisional paradigm regarding anticoagulation relies on weighing the risk of stroke versus the risk of bleeding. By virtue of their age, nearly all patients with atrial fibrillation and AD/ADRD have stroke risk scores that meet the threshold for prescription of an oral anticoagulant. However, the appropriateness of anticoagulation may change with shifting benefits and harms and goals of care over the course of AD/ADRD.Little is currently known about the factors involved in clinical decision-making about anticoagulation for atrial fibrillation in the context of comorbid AD/ADRD. Although a few studies have demonstrated that an AD/ADRD diagnosis is associated with lower levels of anticoagulation, there is a paucity of evidence about how dementia progression influences decisions to continue or discontinue anticoagulant prescription. There has also been little work to understand how clinicians ultimately make these decisions. The proposed work will redress these gaps with a mixed-methods approach to understand the decisions made by clinicians regarding anticoagulation for patients with atrial fibrillation and comorbid AD/ADRD, and how they arrived at these decisions. Contemporary data from the electronic medical record (EMR) of a large dementia care practice will be leveraged to understand functional, clinical, and sociodemographic factors associated with anticoagulant use and discontinuation over the course of AD/ADRD progression. This work will also employ rigorous qualitative methods to capture the range of factors physicians consider and how they integrate these factors when making decisions about anticoagulation for this vulnerable population. This work represents a first step in a research career devoted to promoting optimal decision-making about comorbid chronic conditions for patients with Alzheimer s Disease and Alzheimer s Disease-related dementias. This GEMSSTAR Award would allow the candidate, a geriatrician, to obtain the training and mentorship to further his quantitative and qualitative analysis skills and develop expertise in using EMR data to pursue research at the forefront of clinical geriatrics.
 
15. Project Title: RESEARCH TRAINING IN GERIATRIC CLINICAL EPIDEMIOLOGY
  Leader(s): GILL, THOMAS MICHAEL
    YALE UNIVERSITY
    NIH T32AG019134 / ( 2001 - 2021 )
  Core(s):
  DESCRIPTION (provided by applicant): This is the third competing renewal of the Yale Training Program in Geriatric Clinical Epidemiology and Aging- Related Research. The objective of the Yale Program is to develop a cadre of physician scientists and PhD investigators with expertise in geriatric clinical epidemiology and/or translational aging research who will be equipped to address the myriad of unanswered questions concerning the diagnosis, etiology, treatment, prevention, and prognosis of the health problems experienced by the ever-increasing number of older persons. We will accomplish this objective by providing highly qualified physicians, who are already well trained in geriatrics and/or subspecialties with age-related relevance, and outstanding PhD-trained investigators with 2 to 3 years of rigorous research training. Our trainees will develop skills in each of 10 essential areas: 1) formulation of significant and focused research questions and hypotheses; 2) design of observational, mechanistic and/or experimental studies to address focused research questions; 3) techniques for successful execution of specific study designs; 4) project and/or laboratory management; 5) critical analysis of the scientific literature, including research methods and data quality; 6) interpretation of findings; 7) oral and written communication of scientific methods and findings; 8) development and implementation of strategies for research support; 9) research team approaches and leadership; and 10) budget management. These skills will be developed through a training experience that includes both didactic and experiential components. The didactic curriculum includes courses offered through the Clinical Scholars Program, Investigative Medicine Program and School of Public Health, coupled with several high quality aging-specific training venues at Yale and 'offsite'. The central component of the Yale Program is a mentored research experience, which includes structured meetings with Program Faculty in geriatrics/gerontology and at least one supervised research project tailored to the trainee's experiences and interests, with the goal of producing one or more first- authored, peer-reviewed publications and a grant application to support further research. The Yale Program has successfully recruited and retained a full complement of outstanding trainees during each of the first 14 years, and has successfully placed many of its graduates in tenure-track, research-intensive positions at top- tier academic institutions. For the next five years, we request continued funding for four postdoctoral positions.
 
16. 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.
 
17. Project Title: SYSTEMS IMMUNE PROFILING OF DIVERGENT RESPONSES TO INFECTION
  Leader(s): HAFLER, DAVID A.; MONTGOMERY, RUTH R ;
    YALE UNIVERSITY
    NIH U19AI089992 / ( 2010 - 2021 )
  Core(s):
  The overall goal of the Human Immunology Project Consortium (HIPC) program is to capitalize on recentadvances in immune profiling methods in order to create a novel public resource that characterizes diversestates of the human immune system. We propose to contribute to this program through deepinterrogation and a broad systems approach that will identify molecular signatures of divergenthuman immune responses to infections. The three projects that comprise our U19 each leverage acommon experimental infrastructure to focus on a different infectious diseases: the Lyme diseasespirochete Borrelia burgdorferi, emerging arthropod-borne West Nile virus, and effects of aging onvaccination against influenza. Our goal is to delineate human immune signatures that are associated withthe divergent manifestations in the population, using well-defined patient cohorts and a multidimensionalanalytical approach to quantitatively assess primary human immune cell function. Our program employscutting-edge immune profiling such as multidimensional profiling by CyTOF, metabolomics, nanoscaletechnologies such as MuSIC (MultiSpectral Imaging Cytometry), and RNA-seq on single cells that willinform a systems approach to elucidate the biologic signatures defining immune responsiveness.Commonalities between the responses in different tissues, and to the different infection types, will bedetermined by quantifying signature enrichments, and by identifying conserved active sub-networks in thisimmune-specific functional network.This collaborative U19 takes advantage of enormous strengths across our institutions to tackle achallenging issue in human immunology. The investigators in this proposal have established collaborations,regular interactions, and a track record of shared success. Our three research projects are supported byshared cores for Administration, Data Management and Analysis, Single Cell Immunophenotyping, andClinical Recruitment. The united goal of these varied approaches is to define elements of the immuneresponse that contribute to divergent infection outcomes. This multifactorial, wide-angle view of the immuneresponse will be compiled employing the expertise of each individual approach for Systems Modeling fromdeep interrogation of three sets of stratified patient cohorts. The output of this functional systemsimmunology approach will be definitions of human immune signatures following multiple forms of infectiouschallenges with the ultimate goal of defining future targets for intervention and predicting susceptibility orresistance.
 
18. Project Title: SYSTEMS BIOLOGY TO IDENTIFY BIOMARKERS OF NEONATAL VACCINE IMMUNOGENICITY
  Leader(s): LEVY, OFER
    CHILDREN'S HOSPITAL BOSTON
    NIH U19AI118608 / ( 2016 - 2021 )
  Core(s):
  PROJECT SUMMARYImprovement of early life immunization requires a better understanding of vaccine-induced molecularpathways that underlie protective immunogenicity as Correlates of Protection (CoP). Systems vaccinologyemploying technologies that measure molecular changes ( OMICs ) has provided critical insights into theadult immune response to vaccination, but has yet to be applied to the youngest, despite their need forimproved immunization. We will apply powerful OMIC tools to the neonatal immune response to Hepatitis Bvaccination (HBV). HBV is an ideal model to define mechanisms of successful neonatal immunizationbecause: a) HBV is highly effective (>90% protection) and has a well-characterized CoP (anti-hepatitis Bsurface antigen antibody (anti-HBs)); b) anti-HBs titres directly correlate with protection, i.e. the higher anti-HBs the better and more durable protection; c) anti-HBs titers after the fist (neonatal) dose correlate withtiters after the last; d) anti-HBs levels vary widely between subjects; such inter-subject variability enablespowerful systems vaccinology tools to extract meaningful correlations; e) the neonatal HBV response issensitive to co-administration of Bacille Calmette-Gu rin (BCG), which is routinely given together with HBV inthe Expanded Program of Immunization (EPI); this offers the unique opportunity to characterize this in vivoperturbation via OMICs. Our chosen clinical study sites in the Gambia and Papua New Guinea are amongstthe world's most experienced with respect to neonatal vaccinology. Here, newborns will be immunized withnothing (delayed), HBV, BCG or (HBV + BCG) and peripheral blood pre-/post-immunization collected fortranscriptomic and proteomic analysis as well as immune phenotyping. Project 1 will develop and employcutting edge, cross-platform bioinformatics tools to identify pathways associated with CoP. Project 2, willapply unbiased immune phenotyping analysis tools to the same samples and translate to host immuneparameters the in silico derived OMICs signatures. In Project 3 key molecular signals will be dissected invitro to establish cause and effect. We have optimized all assays to work with small blood volumes anddemonstrated feasibility in our pilot of rapid enrollment, stringently controlled sample collection andprocessing yielding cogent data that already hint at distinct vaccine-induced responses. Our cross-platformvalidation and correlation with CoP in a cohort containing training- and test-sets as well as a validationcohort, will identify biomarkers predicting neonatal vaccine immunogenicity i) pre-vaccination (Overall Aim 1)and ii) post-vaccination (Overall Aim 2). Delineation of the relevant mechanisms in vitro (Overall Aim 3)complements the output of this HIPC. Overall, our work will identify vaccine-induced molecular pathways keyfor successful vaccine-induced neonatal immune responses, thereby enhancing and accelerating vaccinedevelopment for those in greatest need.
 
19. 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.
 
20. 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
2021
  1. 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: | AltScore: 8.4
  2. 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: | AltScore: 114.35
  3. 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
    https://doi.org/10.1007/s12028-020-01160-6 | PMID: 33403581
    Citations: | AltScore: 3.35
  4. 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
    https://doi.org/10.1111/jgs.16900 | PMID: 33170957 | PMCID: PMC7902349
    Citations: 1 | AltScore: 22.22
  5. 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
    https://doi.org/10.1177/0269216320956811 | PMID: 32928066
    Citations: | AltScore: 15.3
  6. 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):
    pii: e001442. https://doi.org/10.1136/openhrt-2020-001442 | PMID: 33452007 | PMCID: PMC7813425
    Citations: 1 | AltScore: NA
  7. 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
    https://doi.org/10.1177/1740774520980070 | PMID: 33678038 | PMCID: PMC8009806
    Citations: | AltScore: NA
  8. 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
    https://doi.org/10.1097/QMH.0000000000000290 | PMID: 33783422
    Citations: | AltScore: 0.5
  9. 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
    https://doi.org/10.1097/CCE.0000000000000325 | PMID: 33458691 | PMCID: PMC7803935
    Citations: | AltScore: 19.25
  10. 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
    https://doi.org/10.1111/jgs.16871 | PMID: 33145752 | PMCID: PMC8186950
    Citations: | AltScore: 65.6
  11. 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
    https://doi.org/10.1097/SLA.0000000000004438 | PMID: 33074902
    Citations: | AltScore: 3.95
  12. 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
    https://doi.org/10.1097/CCM.0000000000004829 | PMID: 33497167 | PMCID: PMC8140984
    Citations: | AltScore: 8.05
  13. 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
    https://doi.org/10.1021/acs.jpcb.0c09193 | PMID: 33464098
    Citations: | AltScore: 7
  14. 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
    https://doi.org/10.1016/j.amjmed.2020.07.020 | PMID: 32805225 | PMCID: PMC7752813
    Citations: | AltScore: 5.7
  15. 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):
    pii: 86. https://doi.org/10.3390/brainsci11010086 | PMID: 33440668 | PMCID: PMC7827274
    Citations: | AltScore: NA
  16. 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
    https://doi.org/10.1016/j.jns.2020.117224 | PMID: 33183779
    Citations: | AltScore: NA
  17. 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
    https://doi.org/10.1016/j.ssmph.2021.100767 | PMID: 33855158 | PMCID: PMC8025052
    Citations: | AltScore: NA
  18. 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
    https://doi.org/10.1053/j.semtcvs.2020.05.001 | PMID: 32439546 | PMCID: PMC7983308
    Citations: 1 | AltScore: NA
  19. 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
    JCI Insight, 2021 Jan 25, 6(2):
    pii: 134218. https://doi.org/10.1172/jci.insight.134218 | PMID: 33290275 | PMCID: PMC7934877
    Citations: 1 | AltScore: 13.15
  20. 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
    Med Care, 2021 May 1, 59(5): 402-409
    https://doi.org/10.1097/MLR.0000000000001527 | PMID: 33821829 | PMCID: PMC8024615
    Citations: | AltScore: 4.2
  21. 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
    Health Aff (Millwood), 2021 May, 40(5): 786-794
    https://doi.org/10.1377/hlthaff.2020.02371 | PMID: 33939509
    Citations: | AltScore: 23.9
  22. 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
    Jt Comm J Qual Patient Saf, 2021 Feb, 47(2): 99-106
    https://doi.org/10.1016/j.jcjq.2020.10.003 | PMID: 33358659
    Citations: | AltScore: NA
  23. 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
    JAMA Netw Open, 2021 Mar 1, 4(3): e211271
    https://doi.org/10.1001/jamanetworkopen.2021.1271 | PMID: 33760091 | PMCID: PMC7991967
    Citations: | AltScore: 30.55
  24. 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
    https://doi.org/10.1186/s12911-021-01463-4 | PMID: 33766011 | PMCID: PMC7995592
    Citations: | AltScore: NA
  25. 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: | AltScore: 9.5
 
2020
  1. Genetic Variation and Response to Neurocritical Illness: a Powerful Approach to Identify Novel Pathophysiological Mechanisms and Therapeutic Targets.
    Acosta JN, Brown SC, Falcone GJ
    Neurotherapeutics, 2020 Jan 23, 17(2): 581-592
    https://doi.org/10.1007/s13311-020-00837-2 | PMID: 31975153 | PMCID: PMC7283396
    Citations: 2 | AltScore: 2.85
  2. Effects of Collateral Status on Infarct Distribution Following Endovascular Therapy in Large Vessel Occlusion Stroke.
    Al-Dasuqi K, Payabvash S, Torres-Flores GA, Strander SM, Nguyen CK, Peshwe KU, Kodali S, Silverman A, Malhotra A, Johnson MH, Matouk CC, Schindler JL, Sansing LH, Falcone GJ, Sheth KN, Petersen NH
    Stroke, 2020 Sep, 51(9): e193-e202
    https://doi.org/10.1161/STROKEAHA.120.029892 | PMID: 32781941 | PMCID: PMC7484023
    Citations: 2 | AltScore: 35.38
  3. Seasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults.
    Avey S, Mohanty S, Chawla DG, Meng H, Bandaranayake T, Ueda I, Zapata HJ, Park K, Blevins TP, Tsang S, Belshe RB, Kaech SM, Shaw AC, Kleinstein SH
    J Immunol, 2020 Mar 15, 204(6): 1661-1673
    https://doi.org/10.4049/jimmunol.1900922 | PMID: 32060136 | PMCID: PMC7755271
    Citations: 1 | AltScore: 9.05
  4. Association of Fish Oil and Physical Activity on Mobility Disability in Older Adults.
    Balachandran A, Gundermann DM, Walkup MP, King AC, Ambrosius WT, Kritchevsky SB, Pahor M, Newman AB, Manini TM
    Med Sci Sports Exerc, 2020 Apr, 52(4): 859-867
    https://doi.org/10.1249/MSS.0000000000002195 | PMID: 31688650 | PMCID: PMC7123515
    Citations: | AltScore: 5
  5. Midlife Study of the Louisville Twins: Connecting Cognitive Development to Biological and Cognitive Aging.
    Beam CR, Turkheimer E, Finkel D, Levine ME, Zandi E, Guterbock TM, Giangrande EJ, Ryan L, Pasquenza N, Davis DW
    Behav Genet, 2020 Mar, 50(2): 73-83
    https://doi.org/10.1007/s10519-019-09983-6 | PMID: 31820295 | PMCID: PMC7033012
    Citations: | AltScore: 0.75
  6. Hospital Volume and Operative Mortality for General Surgery Operations Performed Emergently in Adults.
    Becher RD, DeWane MP, Sukumar N, Stolar MJ, Gill TM, Maung AA, Schuster KM, Davis KA
    Ann Surg, 2020 Aug, 272(2): 288-303
    https://doi.org/10.1097/SLA.0000000000003232 | PMID: 32675542 | PMCID: PMC6803029
    Citations: 5 | AltScore: NA
  7. Geographic Variation in the Utilization of and Mortality After Emergency General Surgery Operations in the Northeastern and Southeastern United States.
    Becher RD, Jin L, Warren JL, Gill TM, DeWane MP, Davis KA, Zhang Y
    Ann Surg, 2020 Jun 9
    https://doi.org/10.1097/SLA.0000000000003939 | PMID: 32516232 | PMCID: PMC7726051
    Citations: | AltScore: NA
  8. Regionalization of emergency general surgery operations: A simulation study.
    Becher RD, Sukumar N, DeWane MP, Gill TM, Maung AA, Schuster KM, Stolar MJ, Davis KA
    J Trauma Acute Care Surg, 2020 Mar, 88(3): 366-371
    https://doi.org/10.1097/TA.0000000000002543 | PMID: 31804419 | PMCID: PMC7472889
    Citations: | AltScore: 12.35
  9. Hospital Variation in Geriatric Surgical Safety for Emergency Operation.
    Becher RD, Sukumar N, DeWane MP, Stolar MJ, Gill TM, Schuster KM, Maung AA, Zogg CK, Davis KA
    J Am Coll Surg, 2020 Jun, 230(6): 966-973.e10
    https://doi.org/10.1016/j.jamcollsurg.2019.10.018 | PMID: 32032720 | PMCID: PMC7409563
    Citations: | AltScore: 13.7
  10. Efficacy of a Self-Help Web-Based Recovery Training in Improving Sleep in Workers: Randomized Controlled Trial in the General Working Population.
    Behrendt D, Ebert DD, Spiegelhalder K, Lehr D
    J Med Internet Res, 2020 Jan 7, 22(1): e13346
    https://doi.org/10.2196/13346 | PMID: 31909725 | PMCID: PMC6996739
    Citations: 2 | AltScore: 4.25
  11. Comparative Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Response to a Physical Activity Intervention in Older Adults: Results From the Lifestyle Interventions and Independence for Elders Study.
    Brown JD, Smith SM, Strotmeyer ES, Kritchevsky SB, Gill TM, Blair SN, Fielding RA, Buford TW, Pahor M, Manini TM
    J Gerontol A Biol Sci Med Sci, 2020 Apr 17, 75(5): 1010-1016
    https://doi.org/10.1093/gerona/glz120 | PMID: 31070702 | PMCID: PMC7164526
    Citations: 2 | AltScore: 4.75
  12. Association of race and ethnicity to incident epilepsy, or epileptogenesis, after subdural hematoma.
    Brown SC, King ZA, Kuohn L, Kamel H, Gilmore EJ, Frontera JA, Murthy S, Kim JA, Omay SB, Falcone GJ, Sheth KN
    Neurology, 2020 Nov 24, 95(21): e2890-e2899
    https://doi.org/10.1212/WNL.0000000000010742 | PMID: 32907969 | PMCID: PMC7734738
    Citations: | AltScore: 3.35
  13. Anticoagulation after intracerebral hemorrhage: a perfect clinical scenario for genetics-based precision medicine.
    Brown SC, Sheth KN, Falcone GJ
    Pharmacogenomics, 2020 Apr, 21(5): 307-309
    https://doi.org/10.2217/pgs-2019-0181 | PMID: 32238090
    Citations: | AltScore: NA
  14. Prevalence and Course of Frailty in Survivors of Critical Illness.
    Brummel NE, Girard TD, Pandharipande PP, Thompson JL, Jarrett RT, Raman R, Hughes CG, Patel MB, Morandi A, Gill TM, Ely EW
    Crit Care Med, 2020 Oct, 48(10): 1419-1426
    https://doi.org/10.1097/CCM.0000000000004444 | PMID: 32618688 | PMCID: PMC7941759
    Citations: 4 | AltScore: 46.3
  15. Global reach of ageism on older persons' health: A systematic review.
    Chang ES, Kannoth S, Levy S, Wang SY, Lee JE, Levy BR
    PLoS One, 2020, 15(1): e0220857
    https://doi.org/10.1371/journal.pone.0220857 | PMID: 31940338 | PMCID: PMC6961830
    Citations: 9 | AltScore: 551.102
  16. Ophthalmic Medication Expenditures and Out-of-Pocket Spending: An Analysis of United States Prescriptions from 2007 through 2016.
    Chen EM, Kombo N, Teng CC, Mruthyunjaya P, Nwanyanwu K, Parikh R
    Ophthalmology, 2020 Oct, 127(10): 1292-1302
    https://doi.org/10.1016/j.ophtha.2020.04.037 | PMID: 32359935 | PMCID: PMC7508869
    Citations: | AltScore: 15.5
  17. Leaving Money on the Table? Suboptimal Enrollment in the New Social Pension Program in China.
    Chen X, Hu L, Sindelar J
    J Econ Ageing, 2020 Feb, 15:
    pii: 100233. https://doi.org/10.1016/j.jeoa.2019.100233 | PMID: 32864327 | PMCID: PMC7453761
    Citations: 1 | AltScore: NA
  18. Older Adults without Desired Surrogates in a Nationally Representative Sample.
    Cohen AB, Costello DM, O'Leary JR, Fried TR
    J Am Geriatr Soc, 2020 Sep 8, 69(1): 114-121
    https://doi.org/10.1111/jgs.16813 | PMID: 32898285 | PMCID: PMC7854949
    Citations: | AltScore: 6.1
  19. Reply to Comment on: End-of-Life Decision Making and Treatment for Patients With Professional Guardians.
    Cohen AB, Fried TR
    J Am Geriatr Soc, 2020 Apr, 68(4): 896-897
    https://doi.org/10.1111/jgs.16387 | PMID: 32112564
    Citations: | AltScore: NA
  20. Physician Practice Patterns for Performing Thoracentesis in Patients Taking Anticoagulant Medications.
    DeBiasi EM, Murphy TE, Araujo KLB, Pisani MA, Puchalski JT
    J Bronchology Interv Pulmonol, 2020 Jan, 27(1): 42-49
    https://doi.org/10.1097/LBR.0000000000000614 | PMID: 31436608 | PMCID: PMC6923589
    Citations: | AltScore: NA
  21. Deep Learning for Automated Measurement of Hemorrhage and Perihematomal Edema in Supratentorial Intracerebral Hemorrhage.
    Dhar R, Falcone GJ, Chen Y, Hamzehloo A, Kirsch EP, Noche RB, Roth K, Acosta J, Ruiz A, Phuah CL, Woo D, Gill TM, Sheth KN, Lee JM
    Stroke, 2020 Feb, 51(2): 648-651
    https://doi.org/10.1161/STROKEAHA.119.027657 | PMID: 31805845 | PMCID: PMC6993878
    Citations: 2 | AltScore: 46.4
  22. Disability and Recovery After Hospitalization for Medical Illness Among Community-Living Older Persons: A Prospective Cohort Study.
    Dharmarajan K, Han L, Gahbauer EA, Leo-Summers LS, Gill TM
    J Am Geriatr Soc, 2020 Mar, 68(3): 486-495
    https://doi.org/10.1111/jgs.16350 | PMID: 32083319 | PMCID: PMC7735402
    Citations: 2 | AltScore: 237.78
  23. Predicting 6-Month Mortality for Older Adults Hospitalized With Acute Myocardial Infarction: A Cohort Study.
    Dodson JA, Hajduk AM, Geda M, Krumholz HM, Murphy TE, Tsang S, Tinetti ME, Nanna MG, McNamara R, Gill TM, Chaudhry SI
    Ann Intern Med, 2020 Jan 7, 172(1): 12-21
    https://doi.org/10.7326/M19-0974 | PMID: 31816630 | PMCID: PMC7695040
    Citations: 3 | AltScore: 97.2
  24. From screening to ascertainment of the primary outcome using electronic health records: Challenges in the STRIDE trial.
    Esserman D
    Clin Trials, 2020 Aug, 17(4): 346-350
    https://doi.org/10.1177/1740774520920898 | PMID: 32408769 | PMCID: PMC7415626
    Citations: 1 | AltScore: NA
  25. Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage.
    Falcone GJ, Kirsch E, Acosta JN, Noche RB, Leasure A, Marini S, Chung J, Selim M, Meschia JF, Brown DL, Worrall BB, Tirschwell DL, Jagiella JM, Schmidt H, Jimenez-Conde J, Fernandez-Cadenas I, Lindgren A, Slowik A, Gill D, Holmes M, Phuah CL, Petersen NH, Matouk Md CN, Gunel M, Sansing L, Bennett D, Chen Z, Sun LL, Clarke R, Walters RG, Gill TM, Biffi A, Kathiresan S, Langefeld CD, Woo D, Rosand J, Sheth KN, Anderson CD, International Stroke Genetics Consortium.
    Ann Neurol, 2020 Apr 11, 88(1): 56-66
    https://doi.org/10.1002/ana.25740 | PMID: 32277781 | PMCID: PMC7523882
    Citations: | AltScore: 20.35
  26. Flattening the disability curve: Rehabilitation and recovery after COVID-19 infection.
    Falvey JR, Ferrante LE
    Heart Lung, 2020 Sep - Oct, 49(5): 440-441
    https://doi.org/10.1016/j.hrtlng.2020.05.001 | PMID: 32457005 | PMCID: PMC7211743
    Citations: 4 | AltScore: 29.95
  27. Home Health Rehabilitation Utilization Among Medicare Beneficiaries Following Critical Illness.
    Falvey JR, Murphy TE, Gill TM, Stevens-Lapsley JE, Ferrante LE
    J Am Geriatr Soc, 2020 Mar 18, 68(7): 1512-1519
    https://doi.org/10.1111/jgs.16412 | PMID: 32187664 | PMCID: PMC7712590
    Citations: 3 | AltScore: 213.15
  28. Functional Loss and Resilience in Intensive Care.
    Ferrante LE, Stevens RD
    Crit Care Med, 2020 Nov, 48(11): 1690-1692
    https://doi.org/10.1097/CCM.0000000000004603 | PMID: 33038158 | PMCID: PMC8091484
    Citations: | AltScore: 7.35
  29. Chronic Disease Decision Making and \What Matters Most\.
    Fried TR, Street RL Jr, Cohen AB
    J Am Geriatr Soc, 2020 Mar, 68(3): 474-477
    https://doi.org/10.1111/jgs.16371 | PMID: 32043559 | PMCID: PMC7197748
    Citations: 2 | AltScore: 15.6
  30. Association between metabolic syndrome and recurrence of nonmuscle-invasive bladder cancer in older adults.
    Garg T, Young AJ, O'Keeffe-Rosetti M, McMullen CK, Nielsen ME, Murphy TE, Kirchner HL
    Urol Oncol, 2020 Sep, 38(9): 737.e17-737.e23
    https://doi.org/10.1016/j.urolonc.2020.04.010 | PMID: 32409197 | PMCID: PMC7438276
    Citations: 2 | AltScore: 0.5
  31. Strategy for addressing research-site overlap in pragmatic clinical trials: lessons learned from the NIH-DOD-VA Pain Management Collaboratory (PMC).
    Geda M, George SZ, Burgess DJ, Scarton DV, Roddy WT, Gordon KS, Pasquina PF, Brandt CA, Kerns RD, Peduzzi P, NIH-DoD-VA Pain Management Collaboratory.
    Trials, 2020 Dec 11, 21(1): 1021
    https://doi.org/10.1186/s13063-020-04941-8 | PMID: 33308289 | PMCID: PMC7731473
    Citations: | AltScore: NA
  32. Plasma neurofilament light predicts mortality in patients with stroke.
    Gendron TF, Badi MK, Heckman MG, Jansen-West KR, Vilanilam GK, Johnson PW, Burch AR, Walton RL, Ross OA, Brott TG, Miller TM, Berry JD, Nicholson KA, Wszolek ZK, Oskarsson BE, Sheth KN, Sansing LH, Falcone GJ, Cucchiara BL, Meschia JF, Petrucelli L
    Sci Transl Med, 2020 Nov 11, 12(569):
    pii: eaay1913. https://doi.org/10.1126/scitranslmed.aay1913 | PMID: 33177179
    Citations: 2 | AltScore: 114.55
  33. Cooperation and conflict in intra-hospital transfers: A qualitative analysis.
    Germack HD, Fekieta R, Campbell Britton M, Feder SL, Rosenberg A, Chaudhry SI
    Nurs Open, 2020 Mar, 7(2): 634-641
    https://doi.org/10.1002/nop2.434 | PMID: 32089862 | PMCID: PMC7024622
    Citations: | AltScore: NA
  34. Effect of a Multifactorial Fall Injury Prevention Intervention on Patient Well-Being: The STRIDE Study.
    Gill TM, Bhasin S, Reuben DB, Latham NK, Araujo K, Ganz DA, Boult C, Wu AW, Magaziner J, Alexander N, Wallace RB, Miller ME, Travison TG, Greenspan SL, Gurwitz JH, Rich J, Volpi E, Waring SC, Manini TM, Min LC, Teresi J, Dykes PC, McMahon S, McGloin JM, Skokos EA, Charpentier P, Basaria S, Duncan PW, Storer TW, Gazarian P, Allore HG, Dziura J, Esserman D, Carnie MB, Hanson C, Ko F, Resnick NM, Wiggins J, Lu C, Meng C, Goehring L, Fagan M, Correa-de-Araujo R, Casteel C, Peduzzi P, Greene EJ
    J Am Geriatr Soc, 2020 Oct 9, 69(1): 173-179
    https://doi.org/10.1111/jgs.16854 | PMID: 33037632 | PMCID: PMC8178516
    Citations: | AltScore: 6.6
  35. Recovery from Severe Disability that Develops Progressively Versus Catastrophically: Incidence, Risk Factors, and Intervening Events.
    Gill TM, Gahbauer EA, Leo-Summers L, Murphy TE
    J Am Geriatr Soc, 2020 Jun 3, 68(9): 2067-2073
    https://doi.org/10.1111/jgs.16567 | PMID: 32495396 | PMCID: PMC7710614
    Citations: | AltScore: 5.05
  36. Cohort Profile: The Precipitating Events Project (PEP Study).
    Gill TM, Han L, Gahbauer EA, Leo-Summers L, Murphy TE
    J Nutr Health Aging, 2020, 24(4): 438-444
    https://doi.org/10.1007/s12603-020-1341-4 | PMID: 32242212 | PMCID: PMC7322244
    Citations: 1 | AltScore: 14.15
  37. Optimizing Retention in a Pragmatic Trial of Community-Living Older Persons: The STRIDE Study.
    Gill TM, McGloin JM, Shelton A, Bianco LM, Skokos EA, Latham NK, Ganz DA, Nyquist LV, Wallace RB, Carnie MB, Dykes PC, Goehring LA, Doyle M, Charpentier PA, Greene EJ, Araujo KL
    J Am Geriatr Soc, 2020 Mar 25, 68(6): 1242-1249
    https://doi.org/10.1111/jgs.16356 | PMID: 32212395 | PMCID: PMC7707554
    Citations: 2 | AltScore: 7.05
  38. Factors Associated With Insidious and Noninsidious Disability.
    Gill TM, Murphy TE, Gahbauer EA, Leo-Summers L, Han L
    J Gerontol A Biol Sci Med Sci, 2020 Oct 15, 75(11): 2125-2129
    https://doi.org/10.1093/gerona/glaa002 | PMID: 31907523 | PMCID: PMC7566549
    Citations: | AltScore: NA
  39. Impact of Baseline Fatigue on a Physical Activity Intervention to Prevent Mobility Disability.
    Glynn NW, Gmelin T, Santanasto AJ, Lovato LC, Lange-Maia BS, Nicklas BJ, Fielding RA, Manini TM, Myers VH, de Rekeneire N, Spring BJ, Pahor M, King AC, Rejeski WJ, Newman AB, Lifestyle Interventions and Independence for Elders Study Group.
    J Am Geriatr Soc, 2020 Mar, 68(3): 619-624
    https://doi.org/10.1111/jgs.16274 | PMID: 31867713 | PMCID: PMC8061638
    Citations: | AltScore: 22.45
  40. Patient Recommendations to Improve the Implementation of and Engagement With Portals in Acute Care: Hospital-Based Qualitative Study.
    Greysen SR, Magan Y, Rosenthal J, Jacolbia R, Auerbach AD, Harrison JD
    J Med Internet Res, 2020 Jan 14, 22(1): e13337
    https://doi.org/10.2196/13337 | PMID: 31934868 | PMCID: PMC6996719
    Citations: 3 | AltScore: 0.75
  41. Risk Model for Decline in Activities of Daily Living Among Older Adults Hospitalized With Acute Myocardial Infarction: The SILVER-AMI Study.
    Hajduk AM, Dodson JA, Murphy TE, Tsang S, Geda M, Ouellet GM, Gill TM, Brush JE, Chaudhry SI
    J Am Heart Assoc, 2020 Oct 20, 9(19): e015555
    https://doi.org/10.1161/JAHA.119.015555 | PMID: 33000681 | PMCID: PMC7792390
    Citations: 1 | AltScore: 10.15
  42. Schizophrenia and Epigenetic Aging Biomarkers: Increased Mortality, Reduced Cancer Risk, and Unique Clozapine Effects.
    Higgins-Chen AT, Boks MP, Vinkers CH, Kahn RS, Levine ME
    Biol Psychiatry, 2020 Aug 1, 88(3): 224-235
    https://doi.org/10.1016/j.biopsych.2020.01.025 | PMID: 32199607 | PMCID: PMC7368835
    Citations: 2 | AltScore: 22.4
  43. The CSF Diversion via Lumbar Drainage to Treat Dialysis Disequilibrium Syndrome in the Critically Ill Neurological Patient.
    Hong CS, Wang K, Falcone GJ
    Neurocrit Care, 2020 Aug, 33(1): 312-316
    https://doi.org/10.1007/s12028-020-00972-w | PMID: 32378129 | PMCID: PMC7223300
    Citations: | AltScore: 1.35
  44. Annual Wellness Visits and Influenza Vaccinations among Older Adults in the US.
    J?rgensen TSH, Allore H, Elman MR, Nagel C, Zhang M, Markwardt S, Qui?ones AR
    J Prim Care Community Health, 2020 Jan-Dec, 11: 2150132720962870
    https://doi.org/10.1177/2150132720962870 | PMID: 33016194 | PMCID: PMC7536477
    Citations: | AltScore: NA
  45. Predictors of Residential Care Admission in Community-Dwelling Older People With Dementia.
    Jamieson H, Abey-Nesbit R, Nishtala PS, Allore H, Han L, Deely JM, Pickering JW
    J Am Med Dir Assoc, 2020 Jul 6, 21(11): 1665-1670
    pii: S1525-8610(20)30351-0. https://doi.org/10.1016/j.jamda.2020.04.021 | PMID: 32646821 | PMCID: PMC7641960
    Citations: | AltScore: 3.2
  46. Genetic underpinnings of cerebral edema in acute brain injury: an opportunity for pathway discovery.
    Kirsch E, Szejko N, Falcone GJ
    Neurosci Lett, 2020 Jun 21, 730: 135046
    https://doi.org/10.1016/j.neulet.2020.135046 | PMID: 32464484 | PMCID: PMC7372633
    Citations: | AltScore: NA
  47. General practitioners' provision of end-of-life care and associations with dying at home: a registry-based longitudinal study.
    Kjellstadli C, Allore H, Husebo BS, Flo E, Sandvik H, Hunskaar S
    Fam Pract, 2020 Jul 23, 37(3): 340-347
    https://doi.org/10.1093/fampra/cmz059 | PMID: 31995182 | PMCID: PMC7377342
    Citations: 2 | AltScore: 1
  48. Pilot Observational Study to Detect Diurnal Variation and Misalignment in Heart Rate Among Critically Ill Patients.
    Knauert MP, Murphy TE, Doyle MM, Pisani MA, Redeker NS, Yaggi HK
    Front Neurol, 2020, 11: 637
    https://doi.org/10.3389/fneur.2020.00637 | PMID: 32760341 | PMCID: PMC7373742
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  49. Cause of death in spontaneous intracerebral hemorrhage survivors: Multistate longitudinal study.
    Kuohn LR, Leasure AC, Acosta JN, Vanent K, Murthy SB, Kamel H, Matouk CC, Sansing LH, Falcone GJ, Sheth KN
    Neurology, 2020 Nov 17, 95(20): e2736-e2745
    https://doi.org/10.1212/WNL.0000000000010736 | PMID: 32917797 | PMCID: PMC7734723
    Citations: | AltScore: 20.9
  50. A rat epigenetic clock recapitulates phenotypic aging and co-localizes with heterochromatin.
    Levine M, McDevitt RA, Meer M, Perdue K, Di Francesco A, Meade T, Farrell C, Thrush K, Wang M, Dunn C, Pellegrini M, de Cabo R, Ferrucci L
    Elife, 2020 Nov 12, 9:
    pii: e59201. https://doi.org/10.7554/eLife.59201 | PMID: 33179594 | PMCID: PMC7661040
    Citations: 1 | AltScore: 45.45
  51. Assessment of Epigenetic Clocks as Biomarkers of Aging in Basic and Population Research.
    Levine ME
    J Gerontol A Biol Sci Med Sci, 2020 Feb 14, 75(3): 463-465
    https://doi.org/10.1093/gerona/glaa021 | PMID: 31995162 | PMCID: PMC7328198
    Citations: 4 | AltScore: NA
  52. Ageism Amplifies Cost and Prevalence of Health Conditions.
    Levy BR, Slade MD, Chang ES, Kannoth S, Wang SY
    Gerontologist, 2020 Jan 24, 60(1): 174-181
    https://doi.org/10.1093/geront/gny131 | PMID: 30423119 | PMCID: PMC7182003
    Citations: 8 | AltScore: 452.992
  53. An Online Pain Education Program for Working Adults: Pilot Randomized Controlled Trial.
    Li Y, Tse MYM
    J Med Internet Res, 2020 Jan 14, 22(1): e15071
    https://doi.org/10.2196/15071 | PMID: 31934865 | PMCID: PMC6996734
    Citations: 4 | AltScore: 4.75
  54. Linking early life risk factors to frailty in old age: evidence from the China Health and Retirement Longitudinal Study.
    Li Y, Xue QL, Odden MC, Chen X, Wu C
    Age Ageing, 2020 Feb 27, 49(2): 208-217
    https://doi.org/10.1093/ageing/afz160 | PMID: 31957780 | PMCID: PMC7047816
    Citations: 3 | AltScore: 12.4
  55. Differences in Admission Blood Pressure Among Causes of Intracerebral Hemorrhage.
    Lin J, Piran P, Lerario MP, Ong H, Gupta A, Murthy SB, D?az I, Stieg PE, Knopman J, Falcone GJ, Sheth KN, Fink ME, Merkler AE, Kamel H
    Stroke, 2020 Feb, 51(2): 644-647
    https://doi.org/10.1161/STROKEAHA.119.028009 | PMID: 31818231
    Citations: 1 | AltScore: 15.35
  56. Leveraging functional annotation to identify genes associated with complex diseases.
    Liu W, Li M, Zhang W, Zhou G, Wu X, Wang J, Lu Q, Zhao H
    PLoS Comput Biol, 2020 Nov, 16(11): e1008315
    https://doi.org/10.1371/journal.pcbi.1008315 | PMID: 33137096 | PMCID: PMC7660930
    Citations: 1 | AltScore: 9.25
  57. Underlying features of epigenetic aging clocks in vivo and in vitro.
    Liu Z, Leung D, Thrush K, Zhao W, Ratliff S, Tanaka T, Schmitz LL, Smith JA, Ferrucci L, Levine ME
    Aging Cell, 2020 Oct, 19(10): e13229
    https://doi.org/10.1111/acel.13229 | PMID: 32930491 | PMCID: PMC7576259
    Citations: 4 | AltScore: 31.7
  58. A Clinic Blueprint for Post-Coronavirus Disease 2019 RECOVERY: Learning From the Past, Looking to the Future.
    Lutchmansingh DD, Knauert MP, Antin-Ozerkis DE, Chupp G, Cohn L, Dela Cruz CS, Ferrante LE, Herzog EL, Koff J, Rochester CL, Ryu C, Singh I, Tickoo M, Winks V, Gulati M, Possick JD
    Chest, 2020 Nov 4, 159(3): 949-958
    pii: S0012-3692(20)35125-4. https://doi.org/10.1016/j.chest.2020.10.067 | PMID: 33159907 | PMCID: PMC7641526
    Citations: 3 | AltScore: 24.4
  59. Chronic polypharmacy with increasing Drug Burden Index (DBI) exacerbates frailty and impairs physical function, with effects attenuated by deprescribing, in aged mice.
    Mach J, Gemikonakli G, Logan C, Vander Wyk B, Allore H, Ekambareshwar S, Kane AE, Howlett SE, de Cabo R, Le Couteur DG, Hilmer SN
    J Gerontol A Biol Sci Med Sci, 2020 Mar 9, 76(6): 1010-1018
    pii: glaa060. https://doi.org/10.1093/gerona/glaa060 | PMID: 32147704 | PMCID: PMC8140051
    Citations: 3 | AltScore: 33.15
  60. Health-care use and cost for multimorbid persons with dementia in the National Health and Aging Trends Study.
    MacNeil-Vroomen JL, Thompson M, Leo-Summers L, Marottoli RA, Tai-Seale M, Allore HG
    Alzheimers Dement, 2020 Jul 30, 16(9): 1224-1233
    https://doi.org/10.1002/alz.12094 | PMID: 32729984
    Citations: | AltScore: 2.75
  61. Development and evaluation of a patient-centered quality indicator for the appropriateness of type 2 diabetes management.
    McCoy RG, Lipska KJ, Van Houten HK, Shah ND
    BMJ Open Diabetes Res Care, 2020 Nov, 8(2):
    pii: e001878. https://doi.org/10.1136/bmjdrc-2020-001878 | PMID: 33234510 | PMCID: PMC7689069
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  62. Sleep in the Aging Population.
    Miner B, Kryger MH
    Sleep Med Clin, 2020 Jun, 15(2): 311-318
    https://doi.org/10.1016/j.jsmc.2020.02.016 | PMID: 32386704
    Citations: 2 | AltScore: 0.25
  63. Race/ethnicity influences outcomes in young adults with supratentorial intracerebral hemorrhage.
    Miyares LC, Falcone GJ, Leasure A, Adeoye O, Shi FD, Kittner SJ, Langefeld C, Vagal A, Sheth KN, Woo D
    Neurology, 2020 Mar 24, 94(12): e1271-e1280
    https://doi.org/10.1212/WNL.0000000000008930 | PMID: 31969467 | PMCID: PMC7274930
    Citations: 1 | AltScore: 36.5
  64. Family Communication in Long-Term Care During a Pandemic: Lessons for Enhancing Emotional Experiences.
    Monin JK, Ali T, Syed S, Piechota A, Lepore M, Mourgues C, Gaugler JE, Marottoli R, David D
    Am J Geriatr Psychiatry, 2020 Dec, 28(12): 1299-1307
    https://doi.org/10.1016/j.jagp.2020.09.008 | PMID: 33004262 | PMCID: PMC7486818
    Citations: 3 | AltScore: 24.8
  65. Mindfulnes-Based Stress Reduction for Older Couples with Metabolic Syndrome: a Pilot Randomized Controlled Trial.
    Monin JK, Sperduto CM, Manigault AW, Dutton A, Ali A, Clark MS, Jastreboff AM
    Mindfulness (N Y), 2020 Apr, 11(4): 917-927
    https://doi.org/10.1007/s12671-019-01301-9 | PMID: 33343762 | PMCID: PMC7748069
    Citations: | AltScore: NA
  66. Prior antiplatelet therapy and haematoma expansion after primary intracerebral haemorrhage: an individual patient-level analysis of CLEAR III, MISTIE III and VISTA-ICH.
    Murthy S, Roh DJ, Chatterjee A, McBee N, Parikh NS, Merkler AE, Navi BB, Falcone GJ, Sheth KN, Awad I, Hanley D, Kamel H, Ziai WC, CLEAR III, MISTIE III and VISTA-ICH Collaborators.
    J Neurol Neurosurg Psychiatry, 2020 Oct 26
    pii: jnnp-2020-323458. https://doi.org/10.1136/jnnp-2020-323458 | PMID: 33106367 | PMCID: PMC8071838
    Citations: | AltScore: 27.05
  67. Non-Traumatic Subdural Hemorrhage and Risk of Arterial Ischemic Events.
    Murthy SB, Wu X, Diaz I, Parasram M, Parikh NS, Iadecola C, Merkler AE, Falcone GJ, Brown S, Biffi A, Ch'ang J, Knopman J, Stieg PE, Navi BB, Sheth KN, Kamel H
    Stroke, 2020 May, 51(5): 1464-1469
    https://doi.org/10.1161/STROKEAHA.119.028510 | PMID: 32178587 | PMCID: PMC7188584
    Citations: 1 | AltScore: 1.95
  68. Risk Factors for Disability After Emergency Department Discharge in Older Adults.
    Nagurney JM, Han L, Leo-Summers L, Allore HG, Gill TM
    Acad Emerg Med, 2020 Dec, 27(12): 1270-1278
    https://doi.org/10.1111/acem.14088 | PMID: 32673434 | PMCID: PMC7749835
    Citations: | AltScore: 5.75
  69. Weight change in heart failure inpatients not associated with 30-day readmission.
    Nanna MG, Sullivan AE, Bazylevska V, L Wong R, Murphy TE, Bellumkonda L, McNamara RL
    Future Cardiol, 2020 Jul, 16(4): 289-296
    https://doi.org/10.2217/fca-2019-0047 | PMID: 32286858 | PMCID: PMC7607390
    Citations: | AltScore: 0.5
  70. Impact of Anticholinergic Burden on Cognitive Performance: A Cohort Study of Community-Dwelling Older Adults.
    Nishtala PS, Allore H, Han L, Jamieson HA, Hilmer SN, Chyou TY
    J Am Med Dir Assoc, 2020 May 8, 21(9): 1357-1358.e3
    pii: S1525-8610(20)30286-3. https://doi.org/10.1016/j.jamda.2020.03.027 | PMID: 32402780 | PMCID: PMC7971451
    Citations: | AltScore: NA
  71. Pathogen burden and leukocyte telomere length in the United States.
    Noppert GA, Feinstein L, Dowd JB, Stebbins RC, Zang E, Needham BL, Meier HCS, Simanek A, Aiello AE
    Immun Ageing, 2020 Nov 19, 17(1): 36
    https://doi.org/10.1186/s12979-020-00206-9 | PMID: 33292353 | PMCID: PMC7677839
    Citations: | AltScore: 2.25
  72. Cardiac rehabilitation in older adults: is it just lifestyle?
    Norekv?l TM, Allore HG
    Heart, 2020 Jul, 106(14): 1035-1037
    https://doi.org/10.1136/heartjnl-2019-316497 | PMID: 32299827 | PMCID: PMC7361003
    Citations: | AltScore: 15.6
  73. Rethinking rehabilitation after percutaneous coronary intervention: a protocol of a multicentre cohort study on continuity of care, health literacy, adherence and costs at all care levels (the CONCARD<sup>PCI</sup>).
    Norekv?l TM, Allore HG, Bendz B, Bjorvatn C, Borregaard B, Br?rs G, Deaton C, F?lun N, Hadjistavropoulos H, Hansen TB, Igland S, Larsen AI, Palm P, Pettersen TR, Rasmussen TB, Schj?tt J, S?gaard R, Valaker I, Zwisler AD, Rotevatn S, CONCARD Investigators.
    BMJ Open, 2020 Feb 12, 10(2): e031995
    https://doi.org/10.1136/bmjopen-2019-031995 | PMID: 32054625 | PMCID: PMC7045256
    Citations: 3 | AltScore: 8
  74. Non-coding RNAs as Regulators of Cellular Senescence in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease.
    Omote N, Sauler M
    Front Med (Lausanne), 2020, 7: 603047
    https://doi.org/10.3389/fmed.2020.603047 | PMID: 33425948 | PMCID: PMC7785852
    Citations: | AltScore: NA
  75. Clinician Perspectives on Incorporating Patients' Values-Based Health Priorities in Decision-Making.
    Ouellet GM, Kiwak E, Costello DM, Green AR, Geda M, Naik AD, Tinetti ME
    J Am Geriatr Soc, 2020 Nov 9, 69(1): 267-269
    https://doi.org/10.1111/jgs.16914 | PMID: 33165913 | PMCID: PMC7839399
    Citations: | AltScore: 7.75
  76. Impact and Lessons From the Lifestyle Interventions and Independence for Elders (LIFE) Clinical Trials of Physical Activity to Prevent Mobility Disability.
    Pahor M, Guralnik JM, Anton SD, Ambrosius WT, Blair SN, Church TS, Espeland MA, Fielding RA, Gill TM, Glynn NW, Groessl EJ, King AC, Kritchevsky SB, Manini TM, McDermott MM, Miller ME, Newman AB, Williamson JD
    J Am Geriatr Soc, 2020 Apr, 68(4): 872-881
    https://doi.org/10.1111/jgs.16365 | PMID: 32105353 | PMCID: PMC7187344
    Citations: 5 | AltScore: 13.35
  77. Liver Fibrosis Indices and Outcomes After Primary Intracerebral Hemorrhage.
    Parikh NS, Kamel H, Navi BB, Iadecola C, Merkler AE, Jesudian A, Dawson J, Falcone GJ, Sheth KN, Roh DJ, Elkind MSV, Hanley DF, Ziai WC, Murthy SB, VISTA-ICH Collaborators.
    Stroke, 2020 Mar, 51(3): 830-837
    https://doi.org/10.1161/STROKEAHA.119.028161 | PMID: 31906832 | PMCID: PMC7048169
    Citations: 4 | AltScore: 5.7
  78. Frailty modifies the intervention effect of chair yoga on pain among older adults with lower extremity osteoarthritis: Secondary analysis of a nonpharmacological intervention trial.
    Park J, Sherman DG, Agogo G, Hoogendijk EO, Liu Z
    Exp Gerontol, 2020 Feb 20, 134: 110886
    https://doi.org/10.1016/j.exger.2020.110886 | PMID: 32088398 | PMCID: PMC7438234
    Citations: | AltScore: NA
  79. Fixed Compared With Autoregulation-Oriented Blood Pressure Thresholds After Mechanical Thrombectomy for Ischemic Stroke.
    Petersen NH, Silverman A, Strander SM, Kodali S, Wang A, Sansing LH, Schindler JL, Falcone GJ, Gilmore EJ, Jasne AS, Cord B, Hebert RM, Johnson M, Matouk CC, Sheth KN
    Stroke, 2020 Mar, 51(3): 914-921
    https://doi.org/10.1161/STROKEAHA.119.026596 | PMID: 32078493 | PMCID: PMC7050651
    Citations: 7 | AltScore: 25.4
  80. Concurrent Hospice Care and Cancer-Directed Treatment for Advanced Lung Cancer and Receipt of Aggressive Care at the End of Life in the Veteran's Health Administration.
    Presley CJ, Han L, O'Leary JR, Zhu W, Corneau E, Chao H, Shamas T, Rose M, Lorenz K, Levy CR, Mor V, Gross CP
    J Palliat Med, 2020 Aug, 23(8): 1038-1044
    https://doi.org/10.1089/jpm.2019.0485 | PMID: 32119800 | PMCID: PMC7404822
    Citations: 2 | AltScore: 1.75
  81. Tracking Multimorbidity Changes in Diverse Racial/Ethnic Populations Over Time: Issues and Considerations.
    Qui?ones AR, Allore HG, Botoseneanu A, Newsom JT, Nagel CL, Dorr DA
    J Gerontol A Biol Sci Med Sci, 2020 Jan 20, 75(2): 297-300
    https://doi.org/10.1093/gerona/glz028 | PMID: 30721991 | PMCID: PMC7176055
    Citations: 2 | AltScore: 7
  82. An Agenda for Addressing Multimorbidity and Racial and Ethnic Disparities in Alzheimer's Disease and Related Dementia.
    Qui?ones AR, Kaye J, Allore HG, Botoseneanu A, Thielke SM
    Am J Alzheimers Dis Other Demen, 2020 Jan-Dec, 35: 1533317520960874
    https://doi.org/10.1177/1533317520960874 | PMID: 32969234 | PMCID: PMC7984095
    Citations: 1 | AltScore: 20.7
  83. Identification of Patients with Nontraumatic Intracranial Hemorrhage Using Administrative Claims Data.
    Sangal RB, Fodeh S, Taylor A, Rothenberg C, Finn EB, Sheth K, Matouk C, Ulrich A, Parwani V, Sather J, Venkatesh A
    J Stroke Cerebrovasc Dis, 2020 Oct 15, 29(12): 105306
    https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.105306 | PMID: 33070110 | PMCID: PMC7686163
    Citations: | AltScore: NA
  84. Deep Versus Lobar Intraparenchymal Hemorrhage: Seizures, Hyperexcitable Patterns, and Clinical Outcomes.
    Sheikh ZB, Stretz C, Maciel CB, Dhakar MB, Orgass H, Petroff OA, Hirsch LJ, Gilmore EJ
    Crit Care Med, 2020 Jun, 48(6): e505-e513
    https://doi.org/10.1097/CCM.0000000000004317 | PMID: 32301843
    Citations: | AltScore: 5.25
  85. Measuring spatial accessibility and within-province disparities in accessibility to county hospitals in Shaanxi Province of Western China based on web mapping navigation data.
    Shen C, Zhou Z, Lai S, Lu L, Dong W, Su M, Zhang J, Wang X, Deng Q, Chen Y, Chen X
    Int J Equity Health, 2020 Jun 18, 19(1): 99
    https://doi.org/10.1186/s12939-020-01217-0 | PMID: 32552715 | PMCID: PMC7302366
    Citations: | AltScore: NA
  86. Long-term Natural History of Atrophy in Eyes with Choroideremia-A Systematic Review and Meta-analysis of Individual-Level Data.
    Shen LL, Ahluwalia A, Sun M, Young BK, Grossetta Nardini HK, Del Priore LV
    Ophthalmol Retina, 2020 Aug, 4(8): 840-852
    https://doi.org/10.1016/j.oret.2020.03.003 | PMID: 32362554 | PMCID: PMC7415675
    Citations: 3 | AltScore: NA
  87. Progression of Unifocal versus Multifocal Geographic Atrophy in Age-Related Macular Degeneration: A Systematic Review and Meta-analysis.
    Shen LL, Sun M, Grossetta Nardini HK, Del Priore LV
    Ophthalmol Retina, 2020 Sep, 4(9): 899-910
    https://doi.org/10.1016/j.oret.2020.03.020 | PMID: 32423772 | PMCID: PMC7483721
    Citations: 1 | AltScore: 0.5
  88. IL-7 receptor alpha defines heterogeneity and signature of human effector memory CD8+ T cells in high dimensional analysis.
    Shin MS, Kim D, Yim K, Park HJ, You S, Dong X, Koumpouras F, Shaw AC, Fan R, Krishnaswamy S, Kang I
    Cell Immunol, 2020 Sep, 355: 104155
    https://doi.org/10.1016/j.cellimm.2020.104155 | PMID: 32619811 | PMCID: PMC7415611
    Citations: | AltScore: 1.75
  89. Dermal Adipocyte Lipolysis and Myofibroblast Conversion Are Required for Efficient Skin Repair.
    Shook BA, Wasko RR, Mano O, Rutenberg-Schoenberg M, Rudolph MC, Zirak B, Rivera-Gonzalez GC, L?pez-Gir?ldez F, Zarini S, Rezza A, Clark DA, Rendl M, Rosenblum MD, Gerstein MB, Horsley V
    Cell Stem Cell, 2020 Jun 4, 26(6): 880-895.e6
    https://doi.org/10.1016/j.stem.2020.03.013 | PMID: 32302523 | PMCID: PMC7853423
    Citations: 9 | AltScore: 34
  90. Comparison of health care utilization among patients affiliated and not affiliated with healthcare professionals in China.
    Si Y, Zhou Z, Su M, Hu H, Yang Z, Chen X
    BMC Health Serv Res, 2020 Dec 3, 20(1): 1118
    https://doi.org/10.1186/s12913-020-05895-y | PMID: 33272275 | PMCID: PMC7713311
    Citations: | AltScore: NA
  91. Leveraging effect size distributions to improve polygenic risk scores derived from summary statistics of genome-wide association studies.
    Song S, Jiang W, Hou L, Zhao H
    PLoS Comput Biol, 2020 Feb, 16(2): e1007565
    https://doi.org/10.1371/journal.pcbi.1007565 | PMID: 32045423 | PMCID: PMC7039528
    Citations: 1 | AltScore: 8.9
  92. Clinically Important Differences for Mobility Measures Derived from the Testosterone Trials.
    Stephens-Shields AJ, Farrar JT, Ellenberg SS, Storer TW, Gill TM, Basaria S, Pahor M, Cauley JA, Ensrud KE, Preston P, Cella D, Snyder PJ, Bhasin S
    J Am Geriatr Soc, 2020 Nov 18, 69(2): 517-523
    https://doi.org/10.1111/jgs.16942 | PMID: 33210287
    Citations: | AltScore: 1
  93. Vasomotor Symptoms and Accelerated Epigenetic Aging in the Women's Health Initiative (WHI).
    Thurston RC, Carroll JE, Levine M, Chang Y, Crandall C, Manson JE, Pal L, Hou L, Shadyab AH, Horvath S
    J Clin Endocrinol Metab, 2020 Apr 1, 105(4):
    pii: dgaa081. https://doi.org/10.1210/clinem/dgaa081 | PMID: 32080740 | PMCID: PMC7069347
    Citations: 4 | AltScore: 6.45
  94. Physician Orders for Life-Sustaining Treatment and Limiting Overtreatment at the End of Life.
    Truog RD, Fried TR
    JAMA, 2020 Feb 16, 323(10): 934-935
    https://doi.org/10.1001/jama.2019.22522 | PMID: 32062673 | PMCID: PMC7429267
    Citations: | AltScore: 160.45
  95. Re-evaluation of the Uplift Clinical Trial Using Age-Appropriate Spirometric Criteria.
    Vaz Fragoso CA, Leo-Summers LS, Gill TM, McAvay GJ
    Chest, 2020 Aug, 158(2): 539-549
    https://doi.org/10.1016/j.chest.2020.02.070 | PMID: 32278783 | PMCID: PMC7417373
    Citations: | AltScore: 1.1
  96. Antihypertensive medications and physical function in older persons.
    Vaz Fragoso CA, McAvay GJ
    Exp Gerontol, 2020 Sep, 138: 111009
    https://doi.org/10.1016/j.exger.2020.111009 | PMID: 32593771 | PMCID: PMC7395796
    Citations: | AltScore: 14.35
  97. Diffusing capacity in normal-for-age spirometry and spirometric impairments, using reference equations from the global lung function initiative.
    Vaz Fragoso CA, Rochester CL, McAvay GJ, Iannone L, Leo-Summers LS
    Respir Med, 2020 Aug - Sep, 170: 106037
    https://doi.org/10.1016/j.rmed.2020.106037 | PMID: 32843169 | PMCID: PMC7453093
    Citations: | AltScore: NA
  98. Comorbid vision and cognitive impairments in older adults hospitalized for acute myocardial infarction.
    Whitson HE, Hajduk AM, Song X, Geda M, Tsang S, Brush J, Chaudhry SI
    J Comorb, 2020 Jan-Dec, 10: 2235042X20940493
    https://doi.org/10.1177/2235042X20940493 | PMID: 32728552 | PMCID: PMC7366400
    Citations: | AltScore: 0.5
  99. The OATH Syndemic: opioids and other substances, aging, alcohol, tobacco, and HIV.
    Womack JA, Justice AC
    Curr Opin HIV AIDS, 2020 Jul, 15(4): 218-225
    https://doi.org/10.1097/COH.0000000000000635 | PMID: 32487817 | PMCID: PMC7422477
    Citations: 2 | AltScore: 0.5
  100. Serious Falls in Middle-Aged Veterans: Development and Validation of a Predictive Risk Model.
    Womack JA, Murphy TE, Bathulapalli H, Smith A, Bates J, Jarad S, Redeker NS, Luther SL, Gill TM, Brandt CA, Justice AC
    J Am Geriatr Soc, 2020 Aug 28, 68(12): 2847-2854
    https://doi.org/10.1111/jgs.16773 | PMID: 32860222 | PMCID: PMC7744431
    Citations: | AltScore: 6.45
  101. Health Inequality among Chinese Older Adults: The Role of Childhood Circumstances.
    Yan B, Chen X, Gill TM
    J Econ Ageing, 2020 Oct, 17:
    https://doi.org/10.1016/j.jeoa.2020.100237 | PMID: 32064224 | PMCID: PMC7021249
    Citations: 4 | AltScore: NA
  102. Bayesian estimation and model selection in group-based trajectory models.
    Zang E, Max JT
    Psychol Methods, 2020 Nov 5
    https://doi.org/10.1037/met0000359 | PMID: 33151722 | PMCID: PMC8109259
    Citations: | AltScore: NA
  103. Associations between prenatal sunshine exposure and birth outcomes in China.
    Zhang X, Wang Y, Chen X, Zhang X
    Sci Total Environ, 2020 Apr 15, 713: 136472
    https://doi.org/10.1016/j.scitotenv.2019.136472 | PMID: 31955080 | PMCID: PMC7047502
    Citations: 1 | AltScore: 6.65
  104. Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures.
    Zhao Y, Amodio M, Vander Wyk B, Gerritsen B, Kumar MM, van Dijk D, Moon K, Wang X, Malawista A, Richards MM, Cahill ME, Desai A, Sivadasan J, Venkataswamy MM, Ravi V, Fikrig E, Kumar P, Kleinstein SH, Krishnaswamy S, Montgomery RR
    PLoS Negl Trop Dis, 2020 Mar, 14(3): e0008112
    https://doi.org/10.1371/journal.pntd.0008112 | PMID: 32150565 | PMCID: PMC7082063
    Citations: 4 | AltScore: 21.25


EXTERNAL ADVISORY BOARD MEMBERS

Ana Maria Cuervo, M.D., Ph.D
Albert Einstein College of Medicine
Serving since 2012 (9 years)

Edward Marcantonio, MD, SM
Beth Israel Deaconess Medical Center
Serving since 2012 (9 years)

Heather Whitson, MD
Duke University School of Medicine & Durham VA Medical Center
Serving since 2016 (5 years)

Neil Alexander, M.D., M.S.
University of Michigan
Serving since 2016 (5 years)


RECOGNITION AND AWARDS (2020-2021)
Andrew Cohen (2020)
  • 2020 Outstanding Junior Investigator of the Year Award, American Geriatrics Society.
Guido Falcone (2020)
  • American Society for Clinical Investigation Young Physician-Scientist Award, Bernard J. Tyson Career Development Award 2020 International Stroke Conference; Robert G. Siekert New Investigator Award in Stroke, 2020 International Stroke Conference and the 2020 Paul Dudley White Scholar (highest ranking abstract), 2020 International Stroke Conference.

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), was appointed as the Director of the Operations Core, and Andrew Cohen, MD, DPhil, assistant professor of medicine (geriatrics) was appointed as the Associate Director of the Research Education Core. Each is now serving as a member of the Yale OAIC Executive Committee, which meets bimonthly.

Minority Grant(s):