Medicine and Health Sciences Commons^™

Development Of An Engineered Extracellular Vesicles-Based Vaccine Platform For Combined Delivery Of Mrna And Protein To Induce Functional Immunity, Xin Luo, Kathleen M Mcandrews, Kent A Arian, Sami J Morse, Viktoria Boeker, Shreyasee V Kumbhar, Yingying Hu, Krishnan K Mahadevan, Kaira A Church, Sriram Chitta, Nicolas T Ryujin, Janine Hensel, Jianli Dai, Dara P Dowlatshahi, Hikaru Sugimoto, Michelle L Kirtley, Valerie S Lebleu, Shabnam Shalapour, Joe H Simmons, Raghu Kalluri

Faculty, Staff and Student Publications

mRNA incorporated in lipid nanoparticles (LNPs) became a new class of vaccine modality for induction of immunity against COVID-19 and ushered in a new era in vaccine development. Here, we report a novel, easy-to-execute, and cost effective engineered extracellular vesicles (EVs)-based combined mRNA and protein vaccine platform (EVX-M+P vaccine) and explore its utility in proof-of-concept immunity studies in the settings of cancer and infectious disease. As a first example, we engineered EVs, natural nanoparticle carriers shed by all cells, to contain ovalbumin mRNA and protein (EVOvaM+P vaccine) to serve as cancer vaccine against ovalbumin-expressing melanoma tumors. EVOvaM+P administration to mice …

High Throughput And Rapid Isolation Of Extracellular Vesicles And Exosomes With Purity Using Size Exclusion Liquid Chromatography, Kshipra S Kapoor, Kristen Harris, Kent A Arian, Lihua Ma, Beatriz Schueng Zancanela, Kaira A Church, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) have emerged as potential biomarkers for diagnosing a range of diseases without invasive procedures. Extracellular vesicles also offer advantages compared to synthetic vesicles for delivery of various drugs; however, limitations in segregating EVs from other particles and soluble proteins have led to inconsistent EV retrieval rates with low levels of purity. Here, we report a new high-yield (88.47 %) and rapid (< 20 min) EV isolation method termed size exclusion - fast protein liquid chromatography (SE-FPLC). We show SE-FPLC can effectively isolate EVs from multiple sources including EVs derived from human and mouse cells and serum samples. The results indicate that SE-FPLC can successfully remove highly abundant protein contaminants such as albumin and lipoprotein complexes, which can represent a major hurdle in large scale isolation of EVs. The high-yield nature of SE-FPLC allows for easy industrial scaling up of EV production for various clinical utilities. SE-FPLC also enables analysis of small volumes of blood for use in point-of-care diagnostics in the clinic. Collectively, SE-FPLC offers many advantages over current EV isolation methods and offers rapid clinical translation.

Oculomics Analysis In Multiple Sclerosis: Current Ophthalmic Clinical And Imaging Biomarkers, Alex Suh, Gilad Hampel, Aditya Vinjamuri, Joshua Ong, Sharif Amit Kamran, Ethan Waisberg, Phani Paladugu, Nasif Zaman, Prithul Sarker, Alireza Tavakkoli, Andrew G Lee

Faculty, Staff and Student Publications

Multiple Sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal damage. Early recognition and treatment are important for preventing or minimizing the long-term effects of the disease. Current gold standard modalities of diagnosis (e.g., CSF and MRI) are invasive and expensive in nature, warranting alternative methods of detection and screening. Oculomics, the interdisciplinary combination of ophthalmology, genetics, and bioinformatics to study the molecular basis of eye diseases, has seen rapid development through various technologies that detect structural, functional, and visual changes in the eye. Ophthalmic biomarkers (e.g., tear composition, …

Social Determinants Of Health And Surgical Desirability Of Outcome Ranking In Older Veterans, Michael A Jacobs, Yubo Gao, Susanne Schmidt, Paula K Shireman, Michael Mader, Carly A Duncan, Leslie R M Hausmann, Karyn B Stitzenberg, Lillian S Kao, Mary Vaughan Sarrazin, Daniel E Hall

Faculty, Staff and Student Publications

Importance: Evaluating how social determinants of health (SDOH) influence veteran outcomes is crucial, particularly for quality improvement.

Objective: To measure associations between SDOH, care fragmentation, and surgical outcomes using a Desirability of Outcome Ranking (DOOR).

Design, setting, and participants: This was a cohort study of US veterans using data from the Veterans Affairs (VA) Surgical Quality Improvement Program (VASQIP; 2013-2019) limited to patients aged 65 years or older with inpatient stays between 2 and 30 days, merged with multiple data sources, including Medicare. Race and ethnicity data were retrieved from VASQIP, Medicare and Medicaid beneficiary summary files, the Veterans Health …

Targeting The Epidermal Growth Factor Receptor Pathway In Chemotherapy-Resistant Triple-Negative Breast Cancer: A Phase Ii Study, Clinton Yam, Miral Patel, Holly A Hill, Ryan Sun, Roland L Bassett, Elisabeth Kong, Senthil Damodaran, Kimberly B Koenig, Sausan Abouharb, Sadia Saleem, Ajit K Bisen, Rashmi K Murthy, David L Ramirez, Gaiane M Rauch, Beatriz E Adrada, Rosalind P Candelaria, Xiaoping Wang, Elizabeth A Mittendorf, Alastair M Thompson, Jason B White, Elizabeth E Ravenberg, Alyson R Clayborn, Qing-Qing Ding, Daniel J Booser, Oluchi Oke, Abenaa M Brewster, Gabriel N Hortobagyi, Nuhad K Ibrahim, Jennifer K Litton, Vicente Valero, Banu K Arun, Debu Tripathy, Jeffrey T Chang, Ken Chen, Anil Korkut, Stacy L Moulder, Lei Huo, Bora Lim, Naoto T Ueno

Faculty, Staff and Student Publications

Purpose: Epidermal growth factor receptor (EGFR) pathway activation causes chemotherapy resistance, and inhibition of the EGFR pathway sensitizes triple-negative breast cancer (TNBC) cells to chemotherapy in preclinical models. Given the high prevalence of EGFR overexpression in TNBC, we conducted a single-arm phase II study of panitumumab (anti-EGFR monoclonal antibody), carboplatin, and paclitaxel as the second phase of neoadjuvant therapy (NAT) in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02593175).

Patients and methods: Patients with early-stage, AC-resistant TNBC, defined as disease progression or ≤80% reduction in tumor volume after four cycles of AC, were eligible for this study and …

Severe Hypertension In Postpartum: How A Nurse Driven Protocol Can Be Used To Decrease A Delay In Treatment, Kayleigh Momme

All Doctor of Nursing Practice (DNP) Scholarly Projects

Problem: The problem at the practicum site is a delay in the treatment of severe range hypertension in postpartum patients due to IV push antihypertensives being administered by resident physicians who are clinically stationed in another building as opposed to the primary nurse.

Aim of the Project: The overall aim is to institute a protocol that will prevent a time delay for the treatment of severe range blood pressures in postpartum patients.

Review of Evidence: Hypertensive disorders during pregnancy and the immediate postpartum period are the leading cause of maternal morbidity and mortality. Obstetric related governing bodies have come to …

Implementation Of Barcode Medication Administration To Reduce Vaccine Errors, Elizabeth R. Schwarz

All Doctor of Nursing Practice (DNP) Scholarly Projects

Problem: In the project organization, a large ambulatory medical group, there have been high rates of vaccine administration errors, particularly within family practice locations, which have the most variety of vaccines given.

Aim of the Project: This project aimed to improve the safety of vaccine administration by implementing barcode medication administration (BCMA) in two family practice locations.

Review of the Evidence: BCMA is increasingly recommended for outpatient settings by patient safety groups like the Institute for Safe Medication Practices (2022). Studies show BCMA can save time, improve vaccine data capture and can decrease medication errors by up to 74% (Evanson …

Reducing 30-Day Post-Stroke Readmissions With A Discharge Checklist Tool, Monika Robinson

All Doctor of Nursing Practice (DNP) Scholarly Projects

Problem: The practice site, a nationally certified stroke care hospital, faced challenges with 30-day post-stroke readmission rates of 8.7%, below the national average of 12.44%. This quality improvement initiative aimed to reduce avoidable readmissions to below 4.7% by implementing a structured education process using a post-stroke checklist for all stroke admissions.

Aim of the Project: The primary goal was to ensure that all stroke patients received consistent discharge education. This was achieved by introducing the American Heart/Stroke Association Post-Stroke Discharge Checklist, aligning with best practices to standardize patient education.

Review of Evidence: Evidence shows inconsistencies in the discharge process, particularly …

Towards Understanding The Relationship Between Hearing Loss And Cognition In Healthy Aging, Samaneh Nemati

Theses and Dissertations

Age-related hearing loss (ARHL) has been increasingly linked to cognitive decline, both directly and through structural brain changes. This study utilized data from the Aging Brain Cohort project at the University of South Carolina (ABC@UofSC) to investigate the relationships between hearing impairments, cognitive performance, and gray matter volume across key brain regions. Specifically, the study aimed to: (i) examine the mediating role of gray matter volume in the relationship between ARHL and cognitive impairments; (ii) investigate the role of regional brain age gap in mediating the relationship between ARHL and cognitive decline; and (iii) delineate the distinctive impact of ARHL …

Factors Affecting The Transition From Pediatric To Adult Care Among Culturally Deaf Young Adults And Young Adults Who Are Deaf Or Hard Of Hearing, Anna Strickland Kell

Theses and Dissertations

Introduction: Adolescence to adulthood is marked by many transitions, including the transition from a pediatric to an adult medical home, also referred to as a health home. For young adults who are culturally Deaf, deaf, or hard of hearing, this transition may be complicated by population-specific needs related to language, literacy, and accessibility. Prior research with transition-age adolescents and young adults who are culturally Deaf, deaf, or hard of hearing has primarily focused on education or hearing health exclusively. The purpose of this research was to investigate the transition of health care from pediatric to adult services among culturally Deaf …

Information Exchange Through Social Networks Links To Adoption Of Child Feeding Practices In Nepal, Mohammad Masudur Rahman

Theses and Dissertations

While there have been notable decreases in child undernutrition (i.e., stunting) over the past few decades, it remains a major concern in Nepal, with 25% of children under the age of five experiencing chronic undernourishment. There is considerable scope for improving nutrition-related behaviors to address this ongoing issue. In Nepal, knowledge regarding appropriate child feeding practices is often inadequate, and thus additional sources of accurate information are required. Information through multiple sources (i.e., interpersonal communication, mass media, and mobile SMS) provides opportunity to reach households who inadequately practice childcare. Information improves knowledge and information exchange (i.e., receiving or sharing) usually …

The Role Of The Physical Therapist In Managing Type 2 Diabetes: Systematic And Qualitative Perspectives, Garrett Matthew Hainline

Theses and Dissertations

Introduction: Physical activity (PA) is an effective tool in the management of Type 2 Diabetes (T2D). PA recommendations for people with T2D are to achieve at least 150 minutes per week of moderate intensity PA. This assists to maintain blood glucose control and reduce cardiovascular disease risk factors. Unfortunately, people with T2D are less likely than their normoglycemic peers to meet PA recommendations.

Veterans of the armed forces experience T2D at even greater levels than the general population, with prevalence at about 20%. In addition, T2D and pre-diabetes are elevated among younger veterans, including those of recent conflicts. Reducing rates …

Demographic Characteristics As Moderators For The Association Between Cigarette Smoking And Type 2 Diabetes Mellitus, Aregash Tewoldeberhan Kidane

Walden Dissertations and Doctoral Studies

Diabetes mellitus is a major public health problem and is associated with increased morbidity, mortality, and healthcare expenditure in the United States. Several studies have been conducted that showed cigarette smoking is associated with an increased incidence and prevalence of diabetes mellitus (DM); however, there is no published information in the literature on the moderating effects of gender/sex and race/ethnicity on this association. The purpose of this quantitative, cross-sectional study was to address this gap in the literature and examine the association between cigarette smoking and DM and the moderating effect of sex and race/ethnicity on the association between cigarette …

The Danger Online Pharmacies Pose On Clients With Eating Disorders In The Prescription Of Glp-1 Agonists For Weight Loss, Madyson R. Frisbie

Selected Honors Theses

This literature review explores the prevalence of utilizing online pharmacies to obtain glucagon-like peptide 1 agonist, Semaglutide, for cosmetic weight loss and the danger that route of obtaining medication places on clients with eating disorders such as anorexia nervosa and bulimia nervosa. In addition, research was conducted to establish practice recommendations to eliminate the possibility of a client with an eating disorder from obtaining a GLP-1 agonist when it is inappropriate for their health status. Various articles were used to gain information about the drug in general, its mechanism of action, indications, positive outcomes, and adverse effects. Additional articles were …

Metastatic Prostate Adenocarcinoma To The Brain - A Clinicopathologic Analysis Of 21 Cases, Namra Ajmal, Yutao Deng, Lawrence C Kenyon, Mark T. Curtis, Mauro Dispagna, Joseph Izes, Li Li

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Brain metastasis from prostate adenocarcinoma (PCa) is rare, often leading to death within a year. Its infrequent occurrence and atypical histopathologic features contribute to lower consideration in the differential diagnosis of tumor brain metastasis. This study aims to assess the clinical characteristics and distinctive histopathologic features of metastatic PCa in the brain for timely and enhanced diagnostic accuracy.

DESIGN: A retrospective search spanning 20 years (2003-2022) was conducted on our archives and identified 21 cases diagnosed as "metastatic prostate adenocarcinoma (mPCa)" in brain biopsies and resections. All existing slides were thoroughly reviewed to evaluate the histopathology of the mPCa. …

Acceptance-Based Process Variables On Postpartum Well-Being And Distress (Database), Alexa Bonacquisti

PCOM Scholarly Works

Dataset for Bonacquisti A, Woodworth EC, Diaz M, Grunberg VA (2024) Acceptance-based process variables on postpartum well-being and distress: The mediating role of psychological flexibility. PLoS ONE 19(12): e0312454. https://doi.org/10.1371/journal.pone.0312454

Effectiveness Of Interventions In The Scope Of Occupational Therapy For Mental Health In Children And Adolescents: A Systematized Review, Shawn Macdonald, Jaden Siegle, Cheyney Loper, Simone Regnier, Danielle Westmark, Stacy Smallfield, Molly Whitlow

Student Systematized Reviews: Occupational Therapy

Importance: 1 in 5 children in the US have a mental health disorder (Larson et al., 2017) which affects health across the lifespan, including engagement in school and play (Rizvi et al., 2024).

Objective: This systemized review explored literature about the effectiveness of mental health interventions for children and adolescents within the occupational therapy (OT) scope of practice.

Data Sources: A medical librarian searched articles from 2019-2024 that were retrieved from PubMed, CINAHL, and PsycINFO.

Study Selection and Data Collection: Studies were included if the outcome measures addressed mental health, interventions were within the scope of OT, participants were children …

Behavioral Factors Associated With Patients' Non-Attendance: A Retrospective Study In An Outpatient Specialty Clinic At A Women's And Children's Hospital In Singapore, Yue Tang, Houyuan Jiang, Jingui Xie, Zhichao Zheng, Chui Yee Loke, Bee Keow Goh

Research Collection Lee Kong Chian School Of Business

Background: This study aimed to identify behavioral factors that affect patient attendance in outpatient clinics, especially those related to rescheduling. Methods: A retrospective study was conducted on 20,386 appointment records for 6,252 patients in an outpatient specialty clinic at a women’s and children’s hospital in Singapore over 34 months (January 2012–October 2014). Multivariate logistic regression was used to analyze the influence of independent variables on appointment no-shows. Results: The average no-show rate of the study population was 28.87%. Patient historical behaviors were significantly associated with appointment attendance. In particular, a larger number of previous visits, more historical no-shows, more historical …

A High-Tech Wreck: Hipaa Roadblocks To Texting Patients, Jonathan Fanaroff

Faculty Scholarship

Protecting the private and confidential information entrusted to health care professionals is a core principle dating back to the Hippocratic Oath. At the same time, effective health communication is essential to build trust and allow patients and families to understand and participate as true members of the team. Although it is not often discussed, there can be a tension between legal security regulations designed to protect confidentiality and the ability to effectively communicate with families. The main source of this tension in the United States is related to the Health Insurance Portability and Accountability Act (HIPAA). At the dawn of …

Prazosin As An Adjuvant To Increase Effectiveness Of Duloxetine In A Rat Model Of Oxaliplatin-Induced Peripheral Neuropathy, Monica A. Wagner, Naji Ayyash

Faculty Scholarship

Objectives: Duloxetine, the only American Society of Clinical Oncology (ASCO) treatment recommended for chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors, is not effective for 40% of survivors. This study examined the ability of a duloxetine-prazosin combination to prevent the development of allodynia and hyperalgesia in a rat model of oxaliplatin-induced peripheral neuropathy (OPIN). Methods: Female (n = 24) and male (n = 41) rats were started on duloxetine (15 mg), prazosin (2 mg), or a duloxetine-prazosin combination one week prior to administration of the chemotherapy drug, oxaliplatin, and continued the duloxetine-prazosin combination for 32 days. Behavioral testing for mechanical allodynia …

Motivating Physical Activity With Fitness Tracking And The Interpersonal Context, Sapphire H. Lin, Sonny Rosenthal, Rich Ling

Research Collection College of Integrative Studies

Many societies have aging populations. Getting older people to exercise can help them achieve a higher quality of life. Fitness tracking and social support can buttress that goal. This study tested the effects of fitness tracking and spousal influence on the physical activity of older adults. In a 2 (blinded vs. feedback) × 2 (individual vs. dyad) between-group experiment, 240 participants received a fitness tracker with a visible or blinded display. They participated in the three-month experiment either individually or with their spouses. Participants who received feedback met daily step counts of 7500 and 10,000 more frequently than those without …

J Mich Dent Assoc October 2024

The Journal of the Michigan Dental Association

Each month, The Journal of the Michigan Dental Association provides news, information, and features about Michigan dentistry to our state's oral health community and the MDA's 6,200+ members. It stands as the primary publication reaching Michigan dentists. The October issue's key content includes:

• Clinical Feature on Endodontics and Vital Pulp Therapy
• Practice Management Feature with Tips on Surviving the Death of a Partner
• An update on Advocacy

Trends And Patterns In Hypertension-Related Deaths: A Comprehensive Analysis Using Center For Disease Control And Prevention's Wide-Ranging Online Data For Epidemiologic Research (Cdc Wonder) Data, Oyinlola O. Fasehun, Joycelyn Adjei-Mensah, Wisdom S. Ugorji, Victoria O. Titus, Oluwatobi O. Asade, Damilola A. Adeyemo, Okelue E. Okobi

School of Medicine Publications

Hypertension (HTN) is a leading cause of cardiovascular morbidity and mortality worldwide. Despite advances in treatment, including the development and use of vasodilator-β-blocker combination and treatment with antihypertensive agents, HTN-related deaths have shown concerning trends. As such, the objective of this study is to examine the trends, disparities, and demographic variations in HTN-related mortality over a decade and to identify key factors contributing to these patterns, including genetics, dietary habits, structural discrimination in access to healthcare, lifestyle choices, and secondary hypertension, which is due to underlying conditions like kidney disease, hormonal disorders, or certain medications. To attain this objective, this …

Evaluating The Impact Of Spot Position Errors On Dose Distribution: A Comparison Between Spot-Scanning Arc Therapy (Sparc) And Intensity-Modulated Proton Therapy (Impt), Peilin Liu, Lewei Zhao, Gang Liu, Xiaoda Cong, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: To quantitatively investigate the impact of spot position error (PE) on the dose distribution in (Spot-scanning arc therapy) SPArc plans versus Intensity-Modulated Proton Therapy (IMPT).

Methods:

Four representative disease sites, including brain, lung, liver, and prostate cancers, were retrospectively selected. Spot position errors were simulated during dynamic SPArc treatment delivery. Two types of errors were generated, including randomized error and systematic error. For each random error scenario, they were further examined across four sub-scenarios (25%, 50%, 75%, and 100% of spots affected) at 1 mm and 2 mm deviations.The randomized errors used two categories with and without Gaussian distribution …

Response To Letter To The Editor Concerning The Article "The Clinical And Economic Impact Of Extended Battery Longevity Of A Substernal Extravascular Implantable Cardioverter Defibrillator"., Bradley P Knight, Nicolas Clémenty, Anish Amin, Ulrika Maria Birgersdotter-Green, Henri Roukoz, Reece Holbrook, Jaimie Manlucu

Heart and Vascular Articles

No abstract provided.

Impact Of Functional Recovery On Patients Having Heart Surgery., Richard J Snow, Lauren Mckown, Geoffrey Blossom, Karen Vogel, Amy Creighton, Jason Shriver, Linda Will, Katie Lentz, Elizabeth Snow, Teresa Caulin-Glaser

Heart and Vascular Articles

OBJECTIVE: To describe the results of a program developed to manage institutional postacute care (IPAC) (postacute skilled nursing, inpatient rehabilitation facility, and long-term acute care) in a CMS Bundled Payments for Care Improvement (BPCI) project for coronary artery bypass graft (CABG) surgery.

STUDY DESIGN: We compared pre- and postutilization patterns during a 3-year period by evaluating risk-adjusted national, state, and other BPCI participant comparisons using a difference-in-differences (DID) analysis in a large urban community tertiary center with a CABG surgery program. Included in the analysis were all Medicare patients receiving CABG surgery at the institution (n = 504), across the …

Exploring Conversations Between A Practitioner And A Person With Dementia, Kotaro Hara, Rosiana Natalie, Wei Soon Cheong, Jingjing Gu, Qianli Xu

Research Collection School Of Computing and Information Systems

In social service centers, practitioners engage in conversations with clients with dementia to facilitate their daily activities and provide support when they are distressed. However, the nature of the care demands the practitioner’s active engagement, which becomes difficult to deliver as the number of people who need care expands. Researchers have been investigating the efficacy of developing agents that assume conversational tasks to alleviate this work. To contribute to the future design of agents for caregiving, we collected and analyzed ten conversations between clients with mild dementia and practitioners who provide care. Our analyses of turn-taking dynamics and dialogue acts …

Reimagining Supportive Approaches At The Intersection Of Mandatory Reporting Policies For The Mother–Infant Dyad Affected By Substance Use, Kelly Mcglothen-Bell, Diana Cartagena, Kathryn J. Malin, Dorothy Vittner, Jacqueline M. Mcgrath, Rebecca Koerner, Ashlee J. Vance, Allison Crawford

College of Nursing Faculty Research and Publications

Background: As rates of substance use during pregnancy persist, the health and optimal development of infants with prenatal substance exposure remain a key priority. Nurses are tasked with identifying and reporting suspected cases of child maltreatment, including abuse and neglect, which is often assumed to be synonymous with substance use during pregnancy. While policies aimed at protecting infants from child abuse and neglect are well intentioned, literature regarding the short- and long-term social and legal implications of mandatory reporting policies is emerging.

Purpose: In this article, we explore the intersections between the condition of substance use in pregnancy and policies …

Left Bundle Branch Area Pacing For Lbbb: Will Left Ventricular Septal Pacing Do?, Daniel J Friedman, Mihail G Chelu

Faculty, Staff and Students Publications

No abstract provided.

Association Of Aortic Valve Calcium With Dementia And Stroke: The Multi-Ethnic Study Of Atherosclerosis, Natalie Marrero, Kunal Jha, Timothy M Hughes, Alexander C Razavi, Jelani K Grant, Ellen Boakye, Khalil Anchouche, Omar Dzaye, Matthew J Budoff, Jerome I Rotter, Xiuqing Guo, Jie Yao, Alexis C Wood, Roger S Blumenthal, Erin D Michos, George Thanassoulis, Wendy S Post, Michael J Blaha, Chinwe Ibeh, Seamus P Whelton

Faculty, Staff and Students Publications

Background and aims: Calcific aortic valve disease is associated with increased thrombin formation, platelet activation, decreased fibrinolysis, and subclinical brain infarcts. We examined the long-term association of aortic valve calcification (AVC) with newly diagnosed dementia and incident stroke in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: AVC was measured using non-contrast cardiac CT at Visit 1. We examined AVC as a continuous (log-transformed) and categorical variable (0, 1-99, 100-299, ≥300). Newly diagnosed dementia was adjudicated using International Classification of Disease codes. Stroke was adjudicated from medical records. We calculated absolute event rates (per 1000 person-years) and multivariable adjusted Cox proportional …