Geriatrics Commons^™

Social Determinants Of Health And Disparate Disability Accumulation In A Cohort Of Black, Hispanic, And White Patients With Multiple Sclerosis, Michael C Robertson, Brian Downer, Paul E Schulz, Rafael Samper-Ternent, Elizabeth J Lyons, Sadaf Arefi Milani

Faculty, Staff and Student Publications

OBJECTIVES: Mexico has a rapidly aging population at risk for cognitive impairment. Social and leisure activities may protect against cognitive decline in older adults. The benefits of these behaviors may vary by patterns of cognitive impairment. The objectives of this study were to identify latent states of cognitive functioning, model the incidence of transitions between these states, and investigate how social and leisure activities were associated with state transitions over a 6-year period in Mexican adults aged 60 and older.

METHODS: We performed latent transition analyses to identify distinct cognitive statuses in the 2012 and 2018 waves of the Mexican …

Longitudinal Associations Between Cognitive Functioning And Depressive Symptoms Among Couples In The Mexican Health And Aging Study, Joan K Monin, Gail Mcavay, Katie Newkirk, Rafael Samper-Ternent

Faculty, Staff and Student Publications

OBJECTIVE: To examine the bidirectional associations between older adult spouses' cognitive functioning and depressive symptoms over time and replicate previous findings from the United States (US) in Mexico.

DESIGN: Longitudinal, dyadic path analysis with the actor-partner interdependence model.

SETTING: Data were from the three most recent interview waves (2012, 2015, and 2018) of the Mexican Health and Aging Study (MHAS), a longitudinal national study of adults aged 50+ years in Mexico.

PARTICIPANTS: Husbands and wives from 905 community-dwelling married couples (N = 1,810).

MEASUREMENTS: The MHAS cognitive battery measured cognitive function. Depressive symptoms were assessed using a modified nine-item Center …

Utilizing Speech Analysis To Differentiate Progressive Supranuclear Palsy From Parkinson’S Disease, Kyurim Kang, Adonay S Nunes, Mansi Sharma, A J Hall, Ram Kinker Mishra, Jose Casado, Rylee Cole, Marc Derhammer, Gregory Barchard, Bijan Najafi, Ashkan Vaziri, Anne-Marie Wills, Alexander Pantelyat

Center on Aging Staff Publications

Introduction: Distinguishing Parkinson's disease (PD) from Progressive supranuclear palsy (PSP) at early disease stages is important for clinical trial enrollment and clinical care/prognostication.

Methods: We recruited 21 participants with PSP(n = 11) or PD(n = 10) with reliable caregivers. Standardized passage reading, counting, and sustained phonation were recorded on the BioDigit Home tablet (BioSensics LLC, Newton, MA USA), and speech features from the assessments were analyzed using the BioDigit Speech platform (BioSensics LLC, Newton, MA USA). An independent t-test was performed to compare each speech feature between PSP and PD participants. We also performed Spearman's correlations to evaluate associations between …

Age-Related Differences In The Contribution Of Systolic Blood Pressure And Biomarkers To Cardiovascular Disease Risk Prediction: The Atherosclerosis Risk In Communities (Aric) Study, Mahmoud Al Rifai, George E Taffet, Kunihiro Matsushita, Salim S Virani, James De Lemos, Amit Khera, Jarrett Berry, Chiadi Ndumele, David Aguilar, Caroline Sun, Ron C Hoogeveen, Elizabeth Selvin, Christie M Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

We sought to determine how biomarkers known to be associated with hypertension-induced end-organ injury complement the use of systolic blood pressure (SBP) for cardiovascular disease (CVD) risk prediction at different ages. Using data from visits 2 (1990 to 1992) and 5 (2011 to 2013) of the Atherosclerosis Risk in Communities (ARIC) study, 3 models were used to predict CVD (composite of coronary heart disease, stroke, and heart failure). Model A included traditional risk factors (TRFs) except SBP, model B-TRF plus SBP, and model C-TRF plus biomarkers (high-sensitivity troponin T [hsTnT] and N-terminal pro-B-type natriuretic peptide [NT-proBNP]). Harrel's C-statistics were used …

Multiancestry Analysis Of The Hla Locus In Alzheimer’S And Parkinson’S Diseases Uncovers A Shared Adaptive Immune Response Mediated By Hla-Drb1*04 Subtypes, Yann Le Guen, Guo Luo, Aditya Ambati, Vincent Damotte, Iris Jansen, Eric Yu, Aude Nicolas, Itziar De Rojas, Thiago Peixoto Leal, Akinori Miyashita, Céline Bellenguez, Michelle Mulan Lian, Kayenat Parveen, Takashi Morizono, Hyeonseul Park, Benjamin Grenier-Boley, Tatsuhiko Naito, Fahri Küçükali, Seth D Talyansky, Selina Maria Yogeshwar, Vicente Sempere, Wataru Satake, Victoria Alvarez, Beatrice Arosio, Michael E Belloy, Luisa Benussi, Anne Boland, Barbara Borroni, María J Bullido, Paolo Caffarra, Jordi Clarimon, Antonio Daniele, Daniel Darling, Stéphanie Debette, Jean-François Deleuze, Martin Dichgans, Carole Dufouil, Emmanuel During, Emrah Düzel, Daniela Galimberti, Guillermo Garcia-Ribas, José María García-Alberca, Pablo García-González, Vilmantas Giedraitis, Oliver Goldhardt, Caroline Graff, Edna Grünblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann-Heimbach, Henne Holstege, Jakub Hort, Yoo Jin Jung, Deckert Jürgen, Silke Kern, Teemu Kuulasmaa, Kun Ho Lee, Ling Lin, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre De Mendonça, Mercè Boada, Pablo Mir, Susanne Moebus, Fermin Moreno, Benedetta Nacmias, Gael Nicolas, Shumpei Niida, Børge G Nordestgaard, Goran Papenberg, Janne Papma, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Oliver Peters, Yolande A L Pijnenburg, Gerard Piñol-Ripoll, Julius Popp, Laura Molina Porcel, Raquel Puerta, Jordi Pérez-Tur, Innocenzo Rainero, Inez Ramakers, Luis M Real, Steffi Riedel-Heller, Eloy Rodriguez-Rodriguez, Owen A Ross, Luis Jose Royo, Dan Rujescu, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Ingmar Skoog, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John Van Swieten, Raquel Sánchez-Valle, Eng-King Tan, Thomas Tegos, Charlotte Teunissen, Jesper Qvist Thomassen, Lucio Tremolizzo, Martin Vyhnalek, Frans Verhey, Margda Waern, Jens Wiltfang, Jing Zhang, Eadb, Gr@Ace Study Group, Degesco Consortium, Demgene, Eadi, Gerad, Asian Parkinson’S Disease Genetics Consortium, Henrik Zetterberg, Kaj Blennow, Zihuai He, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick G Kehoe, Ole A Andreassen, Cornelia Van Duin, Magda Tsolaki, Pascual Sánchez-Juan, Ruth Frikke-Schmidt, Kristel Sleegers, Tatsushi Toda, Anna Zettergren, Martin Ingelsson, Yukinori Okada, Giacomina Rossi, Mikko Hiltunen, Jungsoo Gim, Kouichi Ozaki, Rebecca Sims, Jia Nee Foo, Wiesje Van Der Flier, Takeshi Ikeuchi, Alfredo Ramirez, Ignacio Mata, Agustín Ruiz, Ziv Gan-Or, Jean-Charles Lambert, Michael D Greicius, Emmanuel Mignot

Faculty, Staff and Students Publications

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. …

Patient-Reported Outcomes In Older Breast Cancer Survivors With And Without Prior Chemotherapy Treatment, Taiwo Adesoye, Kai-Ping Liao, Susan Peterson, Liang Li, Daria Zorzi, Holly M Holmes, Mariana Chavez-Macgregor, Sharon H Giordano

Faculty, Staff and Student Publications

BACKGROUND: Little is known about long-term treatment-related symptoms in older breast cancer survivors. We characterized long-term patient-reported symptoms and examined factors associated with the presence and severity of symptoms, and symptom interference with daily activities.

METHODS: Texas Cancer Registry (TCR) Medicare linkage data was used to identify breast cancer patients age 65 and older with local/regional stage disease diagnosed between 2012-2013. Symptom burden was assessed using breast-specific items from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™). Demographic and clinical data also were collected. Logistic regression models were used to assess the association between symptom …

Life’S Essential 8: Optimizing Health In Older Adults, Manish Kumar, Ariela Orkaby, Caitlan Tighe, Dennis T Villareal, Hayley Billingsley, Michael G Nanna, Min Ji Kwak, Namit Rohant, Shreya Patel, Parag Goyal, Scott Hummel, Christina Al-Malouf, Amie Kolimas, Ashok Krishnaswami, Mike W Rich, James Kirkpatrick, Abdulla A Damluji, George A Kuchel, Daniel E Forman, Karen P Alexander

Faculty, Staff and Student Publications

The population worldwide is getting older as a result of advances in public health, medicine, and technology. Older individuals are living longer with a higher prevalence of subclinical and clinical cardiovascular disease (CVD). In 2010, the American Heart Association introduced a list of key prevention targets, known as "Life's Simple 7" to increase CVD-free survival, longevity, and quality of life. In 2022, sleep health was added to expand the recommendations to "Life's Essential 8" (eat better, be more active, stop smoking, get adequate sleep, manage weight, manage cholesterol, manage blood pressure, and manage diabetes). These prevention targets are intended to …

Game-Based Intradialytic Non-Weight-Bearing Exercise Training On Gait Speed And Balance In Older Adults With Diabetes: A Single-Blind Randomized Controlled Trial, M G Finco, Bijan Najafi, He Zhou, Abdullah Hamad, Rania Ibrahim, Fadwa Al-Ali

Center on Aging Staff Publications

Older adults with diabetes receiving hemodialysis have impaired gait speed and balance compared to the general population, which have been associated with increased risks of falls and mortality. This study evaluated the effectiveness of a game-based intradialytic exercise training program (iExergame) on improving gait speed and balance. This was a single-blind randomized controlled trial. The intervention group (IG) received iExergame training using real-time audiovisual feedback with wearable inertial sensors. The control group (CG) received conventional training without any technology. Both trainings were intradialytic, non-weight-bearing, and used ankle range of motion. Gait and balance parameters were collected at baseline and 4-week …

Dynamics Of Anti-Influenza Mucosal Iga Over A Season In A Cohort Of Individuals Living Or Working In A Long-Term Care Facility, Matt D T Hitchings, Brooke A Borgert, Adam Shir, Bingyi Yang, Kyra H Grantz, Jacob Ball, Carlos A Moreno, Kenneth Rand, Parker A Small, Keith R Fowke, Derek A T Cummings

Faculty, Staff and Student Publications

BACKGROUND: Serological surveys are used to ascertain influenza infection and immunity, but evidence for the utility of mucosal immunoglobulin A (IgA) as a correlate of infection or protection is limited.

METHODS: We performed influenza-like illness (ILI) surveillance on 220 individuals living or working in a retirement community in Gainesville, Florida from January to May 2018, and took pre- and postseason nasal samples of 11 individuals with polymerase chain reaction (PCR)-confirmed influenza infection and 60 randomly selected controls. Mucosal IgA against 10 strains of influenza was measured from nasal samples.

RESULTS: Overall, 28.2% and 11.3% of individuals experienced a 2-fold and …

Impact Of Geroscience On Therapeutic Strategies For Older Adults With Cardiovascular Disease: Jacc Scientific Statement, Daniel E Forman, George A Kuchel, John C Newman, James L Kirkland, Elena Volpi, George E Taffet, Nir Barzilai, Ambarish Pandey, Dalane W Kitzman, Peter Libby, Luigi Ferrucci

Faculty, Staff and Students Publications

Geroscience posits that cardiovascular disease (CVD) and other chronic diseases result from progressive erosion of the effectiveness of homeostatic mechanisms that oppose age-related accumulation of molecular damage. This hypothetical common root to chronic diseases explains why patients with CVD are often affected by multimorbidity and frailty and why older age negatively affects CVD prognosis and treatment response. Gerotherapeutics enhance resilience mechanisms that counter age-related molecular damage to prevent chronic diseases, frailty, and disability, thereby extending healthspan. Here, we describe the main resilience mechanisms of mammalian aging, with a focus on how they can affect CVD pathophysiology. We next present novel …

Oleoylethanolamide Facilitates Pparα And Tfeb Signaling And Attenuates Aβ Pathology In A Mouse Model Of Alzheimer’S Disease, Michele M Comerota, Manasee Gedam, Wen Xiong, Feng Jin, Lisheng Deng, Meng C Wang, Jin Wang, Hui Zheng

Faculty, Staff and Students Publications

BACKGROUND: Age is the strongest risk factor for the development of Alzheimer's disease (AD). Besides the pathological hallmarks of β-amyloid (Aβ) plaques and neurofibrillary tangles, emerging evidence demonstrates a critical role of microglia and neuroinflammation in AD pathogenesis. Oleoylethanolamide (OEA) is an endogenous lipid amide that has been shown to promote lifespan and healthspan in C. elegans through regulation of lysosome-to-nucleus signaling and cellular metabolism. The goal of our study was to determine the role of OEA in the mediation of microglial activity and AD pathology using its stable analog, KDS-5104.

METHODS: We used primary microglial cultures and genetic and …

Effectiveness Of An Emergency Department-Based Machine Learning Clinical Decision Support Tool To Prevent Outpatient Falls Among Older Adults: Protocol For A Quasi-Experimental Study, Daniel J Hekman, Amy L Cochran, Apoorva P Maru, Hanna J Barton, Manish N Shah, Douglas Wiegmann, Maureen A Smith, Frank Liao, Brian W Patterson

Faculty, Staff and Student Publications

Background

Emergency department (ED) providers are important collaborators in preventing falls for older adults because they are often the first health care providers to see a patient after a fall and because at-home falls are often preceded by previous ED visits. Previous work has shown that ED referrals to falls interventions can reduce the risk of an at-home fall by 38%. Screening patients at risk for a fall can be time-consuming and difficult to implement in the ED setting. Machine learning (ML) and clinical decision support (CDS) offer the potential of automating the screening process. However, it remains unclear whether …

Accelerated Epigenetic Aging In Older Adults With Hiv Disease: Associations With Serostatus, Hiv Clinical Factors, And Health Literacy, Steven Paul Woods, Antonio L Teixeira, Lais B Martins, Gabriel R Fries, Gabriela D Colpo, Natalia P Rocha

Faculty, Staff and Student Publications

The prevalence of older persons with HIV (PWH) disease has increased considerably in the last 20 years, but our understanding of biological factors of aging and their clinical correlates among PWH remains limited. Study participants were 149 persons aged 50 and older, including 107 PWH and 42 seronegatives. All participants completed a blood draw, research medical evaluation, structured psychiatric interview, neurocognitive assessment, questionnaires, and measures of health literacy. Four epigenetic clocks were generated from stored blood samples using standardized laboratory methods. In regression models adjusting for sex and smoking status, PWH had significantly higher epigenetic aging acceleration values than seronegatives …

The Association Of Race And Ethnicity With Severe Maternal Morbidity Among Individuals Diagnosed With Hypertensive Disorders Of Pregnancy, Ashok Krishnaswami, Michael W Rich, Min Ji Kwak, Parag Goyal, Daniel E Forman, Abdulla A Damluji, Matthew Solomon, Jamal S Rana, Deborah M Kado, Michelle C Odden

Faculty, Staff and Student Publications

AIMS: Randomized clinical trials of hypertension treatment intensity evaluate the effects on incident major adverse cardiovascular events (MACEs) and serious adverse events (SAEs). Occurrences after a non-fatal index event have not been rigorously evaluated. The aim of this study was to evaluate the association of intensive (<120 >mmHg) to standard (<140 >mmHg) blood pressure (BP) treatment with mortality mediated through a non-fatal MACE or non-fatal SAE in 9361 participants in the Systolic Blood Pressure Intervention Trial.

METHODS AND RESULTS: Logistic regression and causal mediation modelling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality …

Associations Between Cancer Predisposition Mutations And Clonal Hematopoiesis In Patients With Solid Tumors, Sebastià Franch-Expósito, Miika Mehine, Ryan N Ptashkin, Kelly L Bolton, Chaitanya Bandlamudi, Preethi Srinivasan, Linda Zhang, Margaret A Goodell, Erika Gedvilaite, Kamal Menghrajani, Pablo Sánchez-Vela, Diana Mandelker, Elizabeth Comen, Larry Norton, Ryma Benayed, Teng Gao, Elli Papaemmanuil, Barry Taylor, Ross Levine, Kenneth Offit, Zsofia Stadler, Michael F Berger, Ahmet Zehir

Center on Aging Staff Publications

Purpose: Clonal hematopoiesis (CH), the expansion of clones in the hematopoietic system, has been linked to different internal and external features such as aging, genetic ancestry, smoking, and oncologic treatment. However, the interplay between mutations in known cancer predisposition genes and CH has not been thoroughly examined in patients with solid tumors.

Methods: We used prospective tumor-blood paired sequencing data from 46,906 patients who underwent Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) testing to interrogate the associations between CH and rare pathogenic or likely pathogenic (P/LP) germline variants.

Results: We observed an enrichment of CH-positive patients among …

Mechanical And Contact Characteristics Of Foam Materials Within Wound Dressings: Theoretical And Practical Considerations In Treatment, Amit Gefen, Paulo Alves, Dimitri Beeckman, José Luis Lázaro-Martínez, Hadar Lev-Tov, Bijan Najafi, Terry Swanson, Kevin Woo

Center on Aging Staff Publications

In the treatment of acute and chronic wounds, the clinical performance of a given foam‐based dressing, and, ultimately, the wound healing and cost of care outcomes are strongly influenced by the mechanical performance of the foam material/s within that dressing. Most aspects of the mechanical performance of foam materials, for example, their stiffness, frictional properties, conformability, swelling characteristics and durability, and the overall mechanical protection provided by a foam‐based dressing to a wound strongly depend on the microstructure of the foam components, particularly on their microtopography, density and porosity. This article, therefore, provides, for the first time, a comprehensive, self‐inclusive …

Prescribing Patterns Of Fall Risk-Increasing Drugs In Older Adults Hospitalized For Heart Failure, Esther Liu, Musarrat Nahid, Mahad Musse, Ligong Chen, Sarah N Hilmer, Andrew Zullo, Min Ji Kwak, Mark Lachs, Emily B Levitan, Monika M Safford, Parag Goyal

Faculty, Staff and Student Publications

BACKGROUND: Older adults hospitalized for heart failure (HF) are at risk for falls after discharge. One modifiable contributor to falls is fall risk-increasing drugs (FRIDs). However, the prevalence of FRIDs among older adults hospitalized for HF is unknown. We describe patterns of FRIDs use and examine predictors of a high FRID burden.

METHODS: We used the national biracial REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a prospective cohort recruited from 2003-2007. We included REGARDS participants aged ≥ 65 years discharged alive after a HF hospitalization from 2003-2017. We determined FRIDs -cardiovascular (CV) and non-cardiovascular (non-CV) medications - …

Guiding Post-Hospital Recovery By 'What Matters:' Implementation Of Patient Priorities Identification In A Va Community Living Center, Katherine C Ritchey, Laurence M Solberg, Sandra Wolfe Citty, Lea Kiefer, Erica Martinez, Caroline Gray, Aanand D Naik

Faculty, Staff and Student Publications

BACKGROUND: Patient priorities care (PPC) is an effective age-friendly health systems (AFHS) approach to aligning care with goals derived from 'what matters'. The purpose of this quality improvement program was to evaluate the fidelity and feasibility of the health priorities identification (HPI) process in VA Community Living Centers (CLC).

METHODS: PPC experts worked with local CLC staff to guide the integration of HPI into the CLC and utilized a Plan-Do-Study-Act (PDSA) model for this quality improvement project. PPC experts reviewed health priorities identification (HPI) encounters and interdisciplinary team (IDT) meetings for fidelity to the HPI process of PPC. Qualitative interviews …

Satisfaction Of Older Patients With Emergency Department Care: Psychometric Properties And Construct Validity Of The Consumer Emergency Care Satisfaction Scale, Peter L T Hoonakker, Pascale Carayon, Roger L Brown, Rebecca Schwei, Rebecca K Green, Mackenzie Rabas, Ly Hoang, Kathryn L Wust, Rachel Rutkowski, Megan E Salwei, Hanna J Barton, Manish N Shah, Michael S Pulia, Brian W Patterson, Paula V W Dail, Sheryl Krause, Denise Buckley, Jennifer Hankwitz, Nicole E Werner

Faculty, Staff and Student Publications

BACKGROUND: Patient satisfaction is an important indicator of quality of care, but its measurement remains challenging. The Consumer Emergency Care Satisfaction Scale (CECSS) was developed to measure patient satisfaction in the emergency department (ED). Although this is a valid and reliable tool, several aspects of the CECSS need to be improved, including the definition, dimension, and scoring of scales.

PURPOSE: The purpose of this study was to examine the construct validity of the CECSS and make suggestions on how to improve the tool to measure overall satisfaction with ED care.

METHODS: We administered 2 surveys to older adults who presented …

Sex- And Ethnic-Specific Patterns In The Incidence Of Hip Fracture Among Older Us Asian And Non-Hispanic White Adults, Joan C Lo, Malini Chandra, David R Lee, Jeanne A Darbinian, Nancy P Gordon, David W Zeltser, Christopher D Grimsrud, Catherine Lee

Faculty, Staff and Student Publications

BACKGROUND: Asian and Pacific Islander (Asian/PI) adults have lower hip fracture incidence than non-Hispanic White (NHW) adults, but data regarding Asian/PI subgroups are limited. We compared hip fracture incidence among older US Asian/PI and NHW populations, including ethnic subgroup differences.

METHODS: Using observational data from a California healthcare system, we identified Asian/PI and NHW adults aged ≥50 years (2000-2019) and followed subjects to 2021 for hip fracture determined by principal/primary hospital diagnosis or by secondary hospital diagnosis with hip/femur procedure codes. Age-adjusted hip fracture incidence was calculated with 95% confidence intervals (CIs). Log-Poisson regression was used to determine fracture incidence …

Differential Effects Of An Ed-To-Home Care Transitions Intervention In An Older Adult Population: A Latent Class Analysis, Rebecca K Green, Kenneth J Nieser, Gwen C Jacobsohn, Amy L Cochran, Thomas V Caprio, Jeremy T Cushman, Amy J H Kind, Michael Lohmeier, Manish N Shah

Faculty, Staff and Student Publications

BACKGROUND: Older adults frequently return to the emergency department (ED) within 30 days of a visit. High-risk patients can differentially benefit from transitional care interventions. Latent class analysis (LCA) is a model-based method used to segment the population and test intervention effects by subgroup.

OBJECTIVES: We aimed to identify latent classes within an older adult population from a randomized controlled trial evaluating the effectiveness of an ED-to-home transitional care program and test whether class membership modified the intervention effect.

RESEARCH DESIGN: Participants were randomized to receive the Care Transitions Intervention or usual care. Study staff collected outcomes data through medical …

Real-World Safety Of Neurohormonal Antagonist Initiation Among Older Adults Following A Heart Failure Hospitalization, Parag Goyal, Andrew R Zullo, Barbara Gladders, Chukwuma Onyebeke, Min Ji Kwak, Larry A Allen, Emily B Levitan, Monika M Safford, Lauren Gilstrap

Faculty, Staff and Student Publications

AIMS: To optimize guideline-directed medical therapy for heart failure, patients may require the initiation of multiple neurohormonal antagonists (NHAs) during and following hospitalization. The safety of this approach for older adults is not well established.

METHODS AND RESULTS: We conducted an observational cohort study of 207 223 Medicare beneficiaries discharged home following a hospitalization for heart failure with reduced ejection fraction (HFrEF) (2008-2015). We performed Cox proportional hazards regression to examine the association between the count of NHAs initiated within 90 days of hospital discharge (as a time-varying exposure) and all-cause mortality, all-cause rehospitalization, and fall-related adverse events over the …

Assessing The Contributions Of Modifiable Risk Factors To Serious Falls And Fragility Fractures Among Older Persons Living With Hiv, Julie A Womack, Terrence E Murphy, Linda Leo-Summers, Jonathan Bates, Samah Jarad, Thomas M Gill, Evelyn Hsieh, Maria C Rodriguez-Barradas, Phyllis C Tien, Michael T Yin, Cynthia A Brandt, Amy C Justice

Faculty, Staff and Students Publications

BACKGROUND: Although 50 years represents middle age among uninfected individuals, studies have shown that persons living with HIV (PWH) begin to demonstrate elevated risk for serious falls and fragility fractures in the sixth decade; the proportions of these outcomes attributable to modifiable factors are unknown.

METHODS: We analyzed 21,041 older PWH on antiretroviral therapy (ART) from the Veterans Aging Cohort Study from 01/01/2010 through 09/30/2015. Serious falls were identified by Ecodes and a machine-learning algorithm applied to radiology reports. Fragility fractures (hip, vertebral, and upper arm) were identified using ICD9 codes. Predictors for both models included a serious fall within …

Cellular Senescence And Frailty In Transplantation, Elizabeth C Lorenz, Latonya J Hickson, Pascale Khairallah, Bijan Najafi, Cassie C Kennedy

Center on Aging Staff Publications

Purpose of review: To summarizes the literature on cellular senescence and frailty in solid-organ transplantation and highlight the emerging role of senotherapeutics as a treatment for cellular senescence.

Recent findings: Solid-organ transplant patients are aging. Many factors contribute to aging acceleration in this population, including cellular senescence. Senescent cells accumulate in tissues and secrete proinflammatory and profibrotic proteins which result in tissue damage. Cellular senescence contributes to age-related diseases and frailty. Our understanding of the role cellular senescence plays in transplant-specific complications such as allograft immunogenicity and infections is expanding. Promising treatments, including senolytics, senomorphics, cell-based regenerative therapies, and behavioral …

Association Of Type 2 Diabetes Subgroups With Cognitive Status Without Modification From Lifestyle Intervention, Michael P Bancks, James Lovato, Ashok Balasubramanyam, Mace Coday, Karen C Johnson, Medha Munshi, Candida Rebello, Lynne E Wagenknecht, Mark A Espeland

Faculty, Staff and Students Publications

CONTEXT: Type 2 diabetes is a risk factor for incident dementia but whether risk and treatment/prevention strategies differ by diabetes subgroup is unknown.

OBJECTIVE: We assessed (1) whether specific type 2 diabetes (T2D) subgroups are associated with mild cognitive impairment (MCI) or probable dementia (PD), and (2) whether T2D subgroups modified the association of the Action for Health in Diabetes (Look AHEAD) multidomain intensive lifestyle intervention (ILI) with MCI/PD.

METHODS: We included 3760 Look AHEAD participants with T2D and overweight or obesity randomly assigned to 10 years of ILI or diabetes support and education. We used k-means clustering techniques with …

Clinical Outcomes Of Immunotherapy Continued Beyond Radiographic Disease Progression In Older Adult Patients With Advanced Non-Small Cell Lung Cancer, Eric K Singhi, Frank Mott, Michelle Worst, Cheuk Hong Leung, J Jack Lee, Brett Carter, Carolyn J Presley, John V Heymach, Mehmet Altan

Faculty, Staff and Student Publications

Immunotherapy is an effective and generally well-tolerated treatment strategy for older adult patients (aged ≥70 years) with advanced non-small cell lung cancer (NSCLC). Unfortunately, most patients who receive immunotherapy eventually exhibit disease progression during treatment. The present study reports on a subset of older adult patients with advanced NSCLC who could effectively continue immunotherapy beyond radiographic disease progression due to perceived clinical benefit. Local consolidative radiotherapy may be used in select older adult patients to prolong the duration of immunotherapy they receive, with a particular consideration of their preexisting co-morbidities, performance status and tolerance of potential toxicities associated with combined …

Leveraging The Electronic Health Record To Implement Emergency Department Delirium Screening, Anita N Chary, Elise Brickhouse, Beatrice Torres, Ilianna Santangelo, Christopher R Carpenter, Shan W Liu, Kyler M Godwin, Aanand D Naik, Hardeep Singh, Maura Kennedy

Faculty, Staff and Students Publications

OBJECTIVE: The aim of this study is to understand how emergency departments (EDs) use health information technology (HIT), and specifically the electronic health record (EHR), to support implementation of delirium screening.

METHODS: We conducted semi-structured interviews with 23 ED clinician-administrators, representing 20 EDs, about how they used HIT resources to implement delirium screening. Interviews focused on challenges participants experienced when implementing ED delirium screening and EHR-based strategies they used to overcome them. We coded interview transcripts using dimensions from the Singh and Sittig sociotechnical model, which addresses use of HIT in complex adaptive health care systems. Subsequently, we analyzed data …

Giant Cell Arteritis In An Elderly Female With Pulmonary Tuberculosis, Ashwin Parchani, Ashish Baweja, Harnoor Singh, Yatharth Malik, Vinod Gupta, Minakshi Dhar, Monika Pathania

Faculty, Staff and Student Publications

Giant cell arteritis (GCA) is a type of systemic vasculitis that primarily affects people over the age of 50 and affects the medium to large arteries. GCA's clinical manifestations can be varied and non-specific, similar to those observed in atherosclerosis. Here, the authors present a case of an elderly woman with pulmonary tuberculosis with GCA masquerading as atherosclerosis.

Naive T Cells Inhibit The Outgrowth Of Intractable Antigen-Activated Memory T Cells: Implications For T-Cell Immunotherapy, Sandhya Sharma, Mae Woods, Naren U Mehta, Tim Sauer, Kathan S Parikh, Michael Schmuck-Henneresse, Huimin Zhang, Birju Mehta, Malcolm K Brenner, Helen E Heslop, Cliona M Rooney

Faculty, Staff and Students Publications

BACKGROUND: The wider application of T cells targeting viral tumor-antigens via their native receptors is hampered by the failure to expand potent tumor-specific T cells from patients. Here, we examine reasons for and solutions to this failure, taking as our model the preparation of Epstein-Barr virus (EBV)-specific T cells (EBVSTs) for the treatment of EBV-positive lymphoma. EBVSTs could not be manufactured from almost one-third of patients, either because they failed to expand, or they expanded, but lacked EBV specificity. We identified an underlying cause of this problem and established a clinically feasible approach to overcome it.

METHODS: CD45RO+CD45RA- memory compartment …

Ultralow-Dose Binary Oncolytic/Helper-Dependent Adenovirus Promotes Antitumor Activity In Preclinical And Clinical Studies, Daniel Wang, Caroline E Porter, Bora Lim, Amanda Rosewell Shaw, Catherine S Robertson, Mae L Woods, Ya Xu, Greyson G W Biegert, Daisuke Morita, Tao Wang, Bambi J Grilley, Helen Heslop, Malcolm K Brenner, Masataka Suzuki

Faculty, Staff and Students Publications

We show that a binary oncolytic/helper-dependent adenovirus (CAdVEC) that both lyses tumor cells and locally expresses the proinflammatory cytokine IL-12 and PD-L1 blocking antibody has potent antitumor activity in humanized mouse models. On the basis of these preclinical studies, we treated four patients with a single intratumoral injection of an ultralow dose of CAdVEC (NCT03740256), representing a dose of oncolytic adenovirus more than 100-fold lower than used in previous trials. While CAdVEC caused no significant toxicities, it repolarized the tumor microenvironment with increased infiltration of CD8 T cells. A single administration of CAdVEC was associated with both locoregional and abscopal …