Epidemiology Commons^™

An Appalachian Perspective On Suicide: A Focus On West Virginia’S Unique Context, Erin Delaney Caswell

Graduate Theses, Dissertations, and Problem Reports (ETD)

INTRODUCTION: The Appalachian region, spanning 13 states from New York to northern Mississippi, experiences the suicide rates in the United States (U.S.), underscoring a public health crisis exacerbated by persistent socioeconomic challenges. West Virginia (WV), the only state entirely within Appalachia, serves as a focal point for understanding the broader suicide crisis in the region, as WV has the highest suicide rates in the region. Moreover, the state has several unique socioeconomic factors, like increased poverty, lower educational attainment, limited access to healthcare, and a high prevalence of chronic pain and substance that may contribute to elevated rates of suicide. …

The Impact Of The Filmarray Meningitis/Encephalitis Panel On Empiric Antibiotic Prescriptions In Patients With Suspected Community-Acquired Meningitis, Aaron Pathak, Caitlynn Pham, Sabra Shay, Todd Lasco, Mayar Al Mohajer

Faculty, Staff and Students Publications

The BioFire® FilmArray® meningitis/encephalitis (FA/ME) panel provides rapid testing for common cerebrospinal fluid pathogens. We compared empiric antibiotic utilization between patients with suspected community-acquired meningitis with and without an FA/ME panel ordered. No significant differences in antibiotic use were found.

Understanding Primary Care Physician Perspectives On The Diagnosis And Management Of Non-Alcoholic Fatty Liver Disease: A Qualitative Study, Natalia I Heredia, Jemima C John, Sonia Singh, Jessica P Hwang, Larkin L Strong, Maya Balakrishnan, Lorna H Mcneill

Faculty, Staff and Students Publications

Primary care physicians (PCPs) are well suited to manage patients with non-alcoholic fatty liver disease (NAFLD), but the limited, existing research suggests inadequate knowledge about the natural history, diagnostic methods, and management of NAFLD. The purpose of this qualitative study is to further understand the knowledge and practices for the diagnosis and management of NAFLD among PCPs. We conducted in-depth interviews with PCPs in the Greater Houston area, addressing current clinical practices used for diagnosing and managing NAFLD, as well as the perceptions of the PCPs regarding the burden of NAFLD on patients. We recorded interviews, transcribed them, coded transcripts, …

A Comprehensive Meta-Analysis Of Tissue Resident Memory T Cells And Their Roles In Shaping Immune Microenvironment And Patient Prognosis In Non-Small Cell Lung Cancer, Aidan Shen, Aliesha Garrett, Cheng-Chi Chao, Dongliang Liu, Chao Cheng, Zhaohui Wang, Chen Qian, Yangzhi Zhu, Junhua Mai, Chongming Jiang

Faculty, Staff and Students Publications

Tissue-resident memory T cells (TRM) are a specialized subset of long-lived memory T cells that reside in peripheral tissues. However, the impact of TRM-related immunosurveillance on the tumor-immune microenvironment (TIME) and tumor progression across various non-small-cell lung cancer (NSCLC) patient populations is yet to be elucidated. Our comprehensive analysis of multiple independent single-cell and bulk RNA-seq datasets of patient NSCLC samples generated reliable, unique TRM signatures, through which we inferred the abundance of TRM in NSCLC. We discovered that TRM abundance is consistently positively correlated with CD4+ T helper 1 cells, M1 macrophages, and resting dendritic cells in the TIME. …

A Descriptive Analysis Of Depressive Symptoms And Body Image By Race/Ethnicity And Nativity Status Among Adolescents, Radhika Prasad

Electronic Theses & Dissertations (2024 - present)

Previous research on the immigrant health paradox among children and adolescents show a mental health advantage yet it is unclear if this applies in a similar magnitude to females (Fillion et al., 2018; Zarei et al., 2023). Immigrants may be exposed to stressors related to immigration and acculturation. Some research suggests that females respond more to stress through internalizing symptoms relative to males (Hall-Lande et al., 2007; Adkins et al., 2009). Given these gender differences in stress response, female immigrants may be particularly vulnerable to the psychological consequences of immigration related stressors. The immigrant health paradox has also overlooked subjective …

Cross-Sectional Analysis Of Primary Care Clinics' Policies, Practices, And Availability Of Patient Support Services During The Covid-19 Pandemic, Kendra Ratnapradipa, Runqiu Wang, Josiane Kabayundo, Walter Marquez Lavenant, Eleanore Nelson, Muskan Ahuja, Ying Zhang, Hongmei Wang

Journal Articles: Epidemiology

BACKGROUND: Healthcare accessibility and utilization are important social determinants of health. Lack of access to healthcare, including missed or no-show appointments, can have negative health effects and be costly to patients and providers. Various office-based approaches and community partnerships can address patient access barriers.

OBJECTIVES: (1) To understand provider perceptions of patient barriers; (2) to describe the policies and practices used to address late or missed appointments, and (3) to evaluate access to patient support services, both in-clinic and with community partners.

METHODS: Mailed cross-sectional survey with online response option, sent to all Nebraska primary care clinics (n = 577) …

Feasibility Assessment Of A Novel Isolation Care Tent In Uganda During The 2022, M. Jana Broadhurst, Rodgers R. Ayebare, David Brett-Major, Sean M. Carroll, Jacob Lacore, Alexander D. Laskey, James V. Lawler, Patricia Lord, Ruben M. Vazquez, Peter Waitt, Mohammed Lamorde

Journal Articles: Epidemiology

This case study describes a feasibility assessment of a novel isolation care tent used in health facilities in Uganda during the 2022 Sudan ebolavirus outbreak. The Isolation System for Treatment and Agile Response to High-Risk Infections Model 1B (ISTARI 1B) is a single-occupancy, portable, negative-pressure isolation tent designed for the safe delivery of standard care to patients with a communicable disease, including Ebola disease (Sudan). At the request of the Uganda Ministry of Health, the Makerere University Infectious Diseases Institute and University of Nebraska Medical Center partnered to evaluate 7 health facilities across 4 districts in Uganda for infrastructure, case …

The Effect Of A Tailored Educational Flyer On Colorectal Cancer Screening Among Rural Residents: Lessons Learned From A Pilot Randomized Trial, Jungyoon Kim, Cheryl Beseler, Melissa Leypoldt, Roma Subramanian, Tamara Robinson, Karen Funkenbusch, Jason Foster, Susan Harris, Aaron Yoder, Emma Hymel, Shinobu Watanabe-Galloway

Journal Articles: Epidemiology

Background/Objectives: Stool-based tests, such as the fecal immunochemical test (FIT), have been widely used for increasing colorectal cancer (CRC) screening. Small media, such as printed materials or flyers, are known to be an effective intervention to increase CRC screening by fecal tests. However, more evidence is needed to determine whether such small media are effective in improving screening uptake of a mailed FIT intervention targeted at rural populations in the USA.

Methods: In this randomized study, 1230 FIT kits were mailed from July to December 2022 to rural Nebraskans aged 45-74 who were not up to date on …

Assessing De Novo Parasite Genomes Assembled Using Only Oxford Nanopore Technologies Minion Data, Kaylee Herzog, Rachel Wu, John M. Hawdon, Peter Nejsum, Joseph R. Fauver

Journal Articles: Epidemiology

In this study, we assessed the quality of de novo genome assemblies for three species of parasitic nematodes (Brugia malayi, Trichuris trichiura, and Ancylostoma caninum) generated using only Oxford Nanopore Technologies MinION data. Assemblies were compared to current reference genomes and against additional assemblies that were supplemented with short-read Illumina data through polishing or hybrid assembly approaches. For each species, assemblies generated using only MinION data had similar or superior measures of contiguity, completeness, and gene content. In terms of gene composition, depending on the species, between 88.9 and 97.6% of complete coding sequences predicted in MinION data only assemblies …

Redesigning Surveillance Through The Global Emerging Infections Surveillance Program, David Brett-Major

Journal Articles: Epidemiology

No abstract provided.

Investigating Fit Kit Completion For Crc Screening In Younger Adults In Rural Areas, Cheryl Beseler, Jungyoon Kim, Melissa Leypoldt, Roma Subramanian, Tamara Robinson, Karen Funkenbusch, Jason M. Foster, Susan Harris, Aaron Yoder, Emma Hymel, Shinobu Watanabe-Galloway

Journal Articles: Epidemiology

Rural regions have higher incidence rates of colorectal cancer (CRC) than urban regions, while screening is lower in rural residents than in urban residents. Rural residents experience barriers to CRC screening due to a lack of access to healthcare, perceived lack of privacy, and other cultural factors. The fecal immunochemical tests (FITs) may provide an inexpensive and convenient alternative for those lacking access to a colonoscopy or sigmoidoscopy. In a clinical trial, we investigated factors that influenced the return of a FIT kit for CRC screening among 1,230 rural residents in a midwestern U.S. state. Participants were selected from two …

Dna Mismatch Repair Defect And Intratumor Heterogeneous Deficiency Differently Impact Immune Responses In Diffuse Large B-Cell Lymphoma, Zijun Y Xu-Monette, Cancan Luo, Li Yu, Yong Li, Govind Bhagat, Alexandar Tzankov, Carlo Visco, Xiangshan Fan, Karen Dybkaer, Ali Sakhdari, Nicholas T Wang, Alyssa F Yuan, April Chiu, Wayne Tam, Youli Zu, Eric D Hsi, Anamarija M Perry, Wenting Song, Dennis O'Malley, Qingyan Au, Harry Nunns, Heounjeong Go, Michael B Møller, Benjamin M Parsons, Santiago Montes-Moreno, Maurilio Ponzoni, Andrés J M Ferreri, Aliyah R Sohani, Jeremy S Abramson, Bing Xu, Ken H Young

Faculty, Staff and Students Publications

Deficient (d) DNA mismatch repair (MMR) is a biomarker predictive of better response to PD-1 blockade immunotherapy in solid tumors. dMMR can be caused by mutations in MMR genes or by protein inactivation, which can be detected by sequencing and immunohistochemistry, respectively. To investigate the role of dMMR in diffuse large B-cell lymphoma (DLBCL), MMR gene mutations and expression of MSH6, MSH2, MLH1, and PMS2 proteins were evaluated by targeted next-generation sequencing and immunohistochemistry in a large cohort of DLBCL patients treated with standard chemoimmunotherapy, and correlated with the tumor immune microenvironment characteristics quantified by fluorescent multiplex immunohistochemistry and gene-expression …

Applying Market Basket Analysis To Determine Complex Coassociations Among Food Allergens In Children With Food Protein-Induced Enterocolitis Syndrome (Fpies), Ankona Banerjee, Kenneth Nobleza, Cynthia Haddad, Joshua Eubanks, Ruchit Rana, Nicholas L Rider, Lisa Pompeii, Duc Nguyen, Sara Anvari

Faculty, Staff and Students Publications

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy, characterized by delayed onset of repetitive vomiting occurring 1 to 4 h following ingestion of a food allergen. Managing FPIES requires strict avoidance of the food trigger. The concern with FPIES is determining the risk of another FPIES food trigger reaction due to potential coassociations with other foods or food groups. An effective statistical approach for analyzing FPIES-related data is essential to identify common coallergens and their associations.

METHODS: This study employed Market Basket Analysis, a data-mining technique, to examine correlations and patterns among allergens in FPIES patients at …

The Next-Generation Dna Vaccine Platforms And Delivery Systems: Advances, Challenges And Prospects, Bowen Lu, Jing Ming Lim, Boyue Yu, Siyuan Song, Praveen Neeli, Navid Sobhani, Pavithra K, Srinivasa Reddy Bonam, Rajendra Kurapati, Junnian Zheng, Dafei Chai

Faculty, Staff and Students Publications

Vaccines have proven effective in the treatment and prevention of numerous diseases. However, traditional attenuated and inactivated vaccines suffer from certain drawbacks such as complex preparation, limited efficacy, potential risks and others. These limitations restrict their widespread use, especially in the face of an increasingly diverse range of diseases. With the ongoing advancements in genetic engineering vaccines, DNA vaccines have emerged as a highly promising approach in the treatment of both genetic diseases and acquired diseases. While several DNA vaccines have demonstrated substantial success in animal models of diseases, certain challenges need to be addressed before application in human subjects. …

A Comprehensive Analysis Of Neuroblastoma Incidence, Survival, And Racial And Ethnic Disparities From 2001 To 2019, Kevin Campbell, David A Siegel, Puja J Umaretiya, Shifan Dai, Andras Heczey, Philip J Lupo, Jeremy M Schraw, Trevor D Thompson, Michael E Scheurer, Jennifer H Foster

Faculty, Staff and Students Publications

BACKGROUND: We characterize the incidence and 5-year survival of children and adolescents with neuroblastoma stratified by demographic and clinical factors based on the comprehensive data from United States Cancer Statistics (USCS) and the National Program of Cancer Registries (NPCR).

METHODS: We analyzed the incidence of neuroblastoma from USCS (2003-2019) and survival data from NPCR (2001-2018) for patients less than 20 years old. Incidence trends were calculated by average annual percent change (AAPC) using joinpoint regression. Differences in relative survival were estimated comparing non-overlapping confidence intervals (CI).

RESULTS: We identified 11,543 primary neuroblastoma cases in USCS. Age-adjusted incidence was 8.3 per …

Prevalence Of Congenital Anomalies According To Maternal Race And Ethnicity, Texas, 1999–2018, Jeremy M Schraw, Elwin Jaime, Charles J Shumate, Mark A Canfield, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: Few studies of congenital anomalies provide prevalence estimates stratified by maternal race/ethnicity. We sought to determine whether the prevalence of a broad spectrum of anomalies varies among offspring of women from different race/ethnic groups.

METHODS: We obtained information on cases with anomalies from the population-based Texas Birth Defects Registry, and denominator data on livebirths among Texas residents during 1999-2018 from the Texas Center for Health Statistics. We estimated the prevalence ratio (PR) and 95% confidence interval (CI) of N = 145 anomalies among offspring of Hispanic and non-Hispanic Black relative to non-Hispanic White women using Poisson regression, adjusting for …

Changes In Patterns Of Referral For Inpatient Rehabilitation Cancer Patients Due To Covid-19: A Retrospective Study, Ekta Gupta, Amy H Ng, Aline Rozman De Moraes, Jack B Fu, Jegy M Tennison, Maaheen Ahmed, Bryan M Fellman, Eduardo Bruera

Faculty, Staff and Students Publications

There is a paucity of literature on the effect of COVID-19 on hospital processes. We hypothesized that COVID-19 was associated with decreased cancer physiatry referrals in 2020. This is a retrospective cohort study of consecutive patients from April to July 2019 and 2020 admitted at an academic quaternary cancer center. The main outcomes were number of hospital admissions, rate, and characteristics of inpatient rehabilitation admissions and change in percentage of physiatry referrals as the primary endpoint. Results showed that in 2019, there were 387 referrals from 10,274 inpatient admissions (3.8%; 95% confidence interval, 2.4-4.2), compared with 337 referrals from 7051 …

Artificial Intelligence-Powered Discovery Of Small Molecules Inhibiting Ctla-4 In Cancer, Navid Sobhani, Dana Rae Tardiel-Cyril, Dafei Chai, Daniele Generali, Jian-Rong Li, Jonathan Vazquez-Perez, Jing Ming Lim, Rachel Morris, Zaniqua N Bullock, Aram Davtyan, Chao Cheng, William K Decker, Yong Li

Faculty, Staff and Students Publications

BACKGROUND/OBJECTIVES: Checkpoint inhibitors, which generate durable responses in many cancer patients, have revolutionized cancer immunotherapy. However, their therapeutic efficacy is limited, and immune-related adverse events are severe, especially for monoclonal antibody treatment directed against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which plays a pivotal role in preventing autoimmunity and fostering anticancer immunity by interacting with the B7 proteins CD80 and CD86. Small molecules impairing the CTLA-4/CD80 interaction have been developed; however, they directly target CD80, not CTLA-4.

SUBJECTS/METHODS: In this study, we performed artificial intelligence (AI)-powered virtual screening of approximately ten million compounds to identify those targeting CTLA-4. We validated the …

Associations Between Flavonoid Intake And Subclinical Atherosclerosis: The Mesa, Nicola P. Bondonno, Benjamin H. Parmenter, Kevin Murray, Catherine P. Bondonno, Lauren C. Blekkenhorst, Alexis C. Wood, Wendy S. Post, Matthew Allison, Michael H. Criqui, Joshua R. Lewis, Jonathan M. Hodgson

Research outputs 2022 to 2026

Background: Flavonoids may play a role in mitigating atherosclerotic cardiovascular diseases, with evidence suggesting effects may differ between vascular beds. Studies examining associations with subclinical markers of atherosclerosis between subpopulations with different underlying risks of atherosclerosis are lacking. METHODS: Among 5599 participants from the MESA (Multi-Ethnic Study of Atherosclerosis), associations between dietary flavonoid intakes (estimated from a food frequency questionnaire) and subclinical measures of atherosclerosis (ankle-brachial index, carotid plaques and intima-media thickness, and coronary artery calcification) were examined using repeated measures models. Exposures and outcomes were measured at exam 1 (2000-2002) and exam 5 (2010-2011). Stratified analyses and interaction terms …

Flavonoid Intakes, Chronic Obstructive Pulmonary Disease, Adult Asthma, And Lung Function: A Cohort Study In The Uk Biobank, Nicola P. Bondonno, Benjamin H. Parmenter, Alysha S. Thompson, Amy Jennings, Kevin Murray, Daniel Bech Rasmussen, Anna Tresserra-Rimbau, Tilman Kühn, Aedín Cassidy

Research outputs 2022 to 2026

Background: Given their antioxidative stress, anti-allergic, anti-inflammatory, and immune-modulating effects, flavonoids are hypothesized to play a role in preventing chronic obstructive pulmonary disease (COPD) and asthma. Objectives: This cohort study aimed to examine associations between flavonoid intake and COPD, asthma, and lung function. Methods: Among 119,466 participants of the UK Biobank, median [interquartile range] age of 60 [53, 65] y, we estimated intakes of flavonoids, flavonoid-rich foods, and a flavodiet score from 24-h diet assessments. Prospective associations with both incident COPD and asthma and cross-sectional associations with measures of lung function [%predicted forced expiratory volume in 1s (FEV1); and FEV1/forced …

Plant But Not Animal Sourced Nitrate Intake Is Associated With Lower Dementia-Related Mortality In The Australian Diabetes, Obesity, And Lifestyle Study, Anjana Rajendra, Nicola P. Bondonno, Liezhou Zhong, Simone Radavelli-Bagatini, Kevin Murray, Stephanie R. Rainey-Smith, Samantha L. Gardener, Lauren C. Blekkenhorst, Dianna J. Magliano, Jonathan E. Shaw, Robin M. Daly, Kaarin J. Anstey, Joshua R. Lewis, Jonathan M. Hodgson, Catherine P. Bondonno

Research outputs 2022 to 2026

Introduction: Dietary nitrate is potentially beneficial for cardiovascular, cerebrovascular, and nervous systems due to its role as a nitric oxide (NO) precursor. Increased nitrate intake improves cardiovascular health and therefore could protect against dementia, given the cardiovascular-dementia link. Objective: To investigate the association between source-dependent nitrate intake and dementia-related mortality. As individuals with diabetes are at higher risk of dementia, a secondary aim was to investigate if the associations between nitrate and dementia varied by diabetes mellitus (DM) and pre-diabetes status. Methods: This study involved 9,149 participants aged ≥25 years from the well-characterised Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study …

Risk Factors Of Under-Five And Infant Mortality: An Umbrella Review Of Systematic Reviews And Meta-Analyses, Bereket Kefale, Jonine Jancey, Amanuel T. Gebremedhin, Sylvester Dodzi Nyadanu, Daniel G. Belay, Gavin Pereira, Gizachew A. Tessema

Research outputs 2022 to 2026

Background: Ensuring child survival is a critical global challenge, requiring a robust and comprehensive understanding of the risk factors contributing to under-five mortality (U5M). We aimed to synthesise and summarise the current available evidence on risk factors of U5M and infant mortality worldwide to inform global child health programmes.

Methods: We searched six major databases (Embase, Medline, Scopus, CINAHL, Web of Science, and Global Health) and repositories of systematic reviews, as well as grey literature sources to identify systematic reviews and meta-analyses that examined the associations between risk factors of U5M and infant mortality between 1 January 1990 and 4 …

Source-Specific Nitrate Intake And All-Cause Mortality In The Danish Diet, Cancer, And Health Study, Nicola P. Bondonno, Pratik Pokharel, Catherine P. Bondonno, Dorit W. Erichsen, Liezhou Zhong, Jörg Schullehner, Kirsten Frederiksen, Cecilie Kyrø, Peter Fjeldstad Hendriksen, Jonathan M. Hodgson, Frederik Dalgaard, Lauren C. Blekkenhorst, Ole Raaschou-Nielsen, Torben Sigsgaard, Christina C. Dahm, Anne Tjønneland, Anja Olsen

Research outputs 2022 to 2026

Introduction: Nitrate and nitrite are naturally occurring in both plant- and animal-sourced foods, are used as additives in the processing of meat, and are found in water. There is growing evidence that they exhibit a spectrum of health effects, depending on the dietary source. The aim of the study was to examine source-dependent associations between dietary intakes of nitrate/nitrite and both all-cause and cause-specific mortality. Methods: In 52,247 participants of the Danish Diet, Cancer and Health Study, associations between source-dependent nitrate and nitrite intakes––calculated using comprehensive food composition and national drinking water quality monitoring databases––and all-cause, cardiovascular disease (CVD)-related, and …

Pulmonary Embolism Response Teams. A Description Of The First 36-Month Australian Experience, Bapti Roy, Jin Gun Cho, Luke Baker, Liza Thomas, Jennifer Curnow, John J. Harvey, Paul Geenty, Ashoke Banerjee, Kevin Lai, Mauro Vicaretti, Odette Erksine, Jane Li, Rafid Alasady, Vanessa Wong, Jian E. Tai, Caitlin Thirunavukarasu, Imran Haque, Jimmy Chien

Research outputs 2022 to 2026

Background: High/intermediate-risk pulmonary embolism (PE) confers increased risk of cardiovascular morbidity and mortality. International guidelines recommend the formation of a PE response team (PERT) for PE management because of the complexity of risk stratification and emerging treatment options. However, there are currently no available Australian data regarding outcomes of PE managed through a PERT. Aims: To analyse the clinical and outcome data of patients from an Australian centre with high/intermediate-risk PE requiring PERT-guided management. Methods: We performed a retrospective observational study of 75 consecutive patients with high/intermediate-risk PE who had PERT involvement, between August 2018 and July 2021. We recorded …

Lessons Learned: Drive-Through Covid-19 Clinic Testing During An Adaptive Epidemic Response And A Point-Of-Care Test Assessment Of A Computer-Read Rapid Lateral Flow Immunoassay With Fluorescence-Based Detection, Leah Rankine-Wilson, Teresa Oncken, Irshan Basrewan, Courtney Jeffery, Todd M. Pryce, Rebecca Wake, Aus A.L. Molan, T. F. Paton, Tim J.J. Inglis

Research outputs 2022 to 2026

Background. The COVID-19 pandemic demonstrated a need for robust SARS-CoV-2 test evaluation infrastructure to underpin biosecurity and protect the population during a pandemic health emergency. Gap statement. The first generation of rapid antigen tests was less accurate than molecular methods due to their inherent sensitivity and specificity shortfalls, compounded by the consequences of self-testing. This created a need for more accurate point-of-care SARS-CoV-2 detection methods. Aim. Here we present the lessons-learned during the COVID-19 emergency response in Western Australia including the detailed set-up, evaluation and operation of rapid antigen test in a state-run drive-through sample collection service during the COVID-19 …

Specific Vegetable Types Are Associated With Lower Long-Term Risk For Late-Life Dementia: The Perth Longitudinal Study Of Aging Women, Negar Ghasemifard, Simone Radavelli-Bagatini, Simon M. Laws, Helen Macpherson, Emma Stevenson, Jonathan M. Hodgson, Richard L. Prince, Joshua R. Lewis, Marc Sim

Research outputs 2022 to 2026

This study examined the relationship between total vegetable intake, including specific vegetable types with long-term late-life dementia (LLD) risk in older Australian women. 1206 community-dwelling older women aged ≥70 years were included. Consumption of total vegetable intake and vegetable types (yellow/orange/red [YOR], cruciferous, allium, green leafy vegetables [GLV], and legumes) were estimated using a validated food frequency questionnaire at baseline (1998). LLD was considered any form of dementia occurring after 80 years of age. LLD events (comprising hospitalisation and/or death) were obtained from linked health records. Associations were examined using restricted cubic splines within multivariable-adjusted (including APOE4 genotype) Cox proportional …