Epidemiology & Biostatistics
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Item CLIMATE CHANGE RELATED EXTREME EVENTS AND ADVERSE HEALTH OUTCOMES AMONG HEMODIALYSIS PATIENTS(2024) Song, Hyeonjin; Sapkota, Amir AS; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The increased frequency and intensity of extreme heat events (EHEs) and wildfires due to climate change are posing significant threats to vulnerable communicates including end-stage kidney disease (ESKD) patients. The specific aims of this dissertation are to Aim 1) Examine the association between EHEs exposure and serum concentrations of sodium and potassium among hemodialysis patients in the Western U.S. (2008-2018), Aim 2) Quantify the mortality and hospitalization risk associated with exposure to 2023 Canadian wildfire-related air pollution in the Eastern U.S., and Aim 3) Investigate how EHEs modify the association between wildfire-related air pollution exposure and the risk of mortality and hospitalization among hemodialysis patients in the Western U.S. (2010-2018). We analyzed health records of patients who receiving hemodialysis treatment at Fresenius Kidney Care clinics. We used the 10°C increase in daily average temperature and daily extreme heat events (EHEs) of each county as the primary exposures. The presence of wildfire smoke plume and wildfire fine particulate matter (PM2.5) concentrations for each clinic were measured using satellite-derived smoke polygons (Hazard Mapping System) and ground-based PM2.5 monitors (Air Quality System). We estimated mean serum sodium and potassium change per 10 °C increase in daily average ambient temperature using random intercepts linear mixed-effects models. We employed a time-stratified case-crossover analysis with conditional quasi-Poisson model to investigate the risks of mortality and hospitalization associated with exposure to wildfire-related air pollution and EHEs. In the first study, a 10°C increase in daily average temperature was associated with 0.43 mEq/L (95% Confidence Interval [CI]: 0.47, 0.59) increase in serum sodium during July-August. The serum sodium was 0.15 mEq/L (95% CI: 0.10, 0.20) higher during EHE days compared to non-EHE days. The serum potassium level did not show a significant change. In the second study, during June-July 2023, the presence of wildfire smoke plume was associated with an 18% increase in all-cause mortality risk (Rate Ratio [RR]:1.18; 95% CI: 1.13, 1.24) and a 3% increase in all-cause hospitalization risk (RR:1.03; 95% CI: 1.00, 1.07). A 10-μg/m3 increase in wildfire-related PM2.5 was associated with a 139% increase in all-cause mortality (RR: 2.39; 95% CI: 1.79, 3.18) and a 33% increase in all-cause hospitalization (RR:1.33; 95% CI: 1.10, 1.62). In the third study, we observed significant interactions between EHEs and wildfire smoke plume for mortality RRs among the hemodialysis patients in the Western U.S. Mortality risk was considerably higher when hemodialysis patients were simultaneously exposed to wildfire smoke plume and EHE compared to wildfire smoke plume alone (RR: 1.52; 95% CI: 1.25, 1.86 vs. RR: 1.15; 95% CI: 1.08, 1.23). We did not observe a significant interaction for all-cause hospitalization. Our findings underscore the need to revise operational and care protocols to prepare for such potential join exposures to extreme events that are exacerbated by ongoing climate change. Future work should focus on developing early warning systems to enhance resilience against such threats.Item COVID-19 Vaccine Hesitancy and Uptake in the United States Considered Through the Lens of Health Behavior Theory(2024) Kauffman, Lauren Emily; Nguyen, Quynh; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Given the low COVID-19 vaccine uptake rates in many areas of the United States despite their demonstrated safety and effectiveness, COVID-19 vaccine hesitancy and vaccination barriers continue to be critical areas of research in epidemiology and behavioral health science. This series of studies focuses on COVID-19 vaccine hesitancy and vaccination barriers, as they relate to vaccination intention and vaccine uptake, considered in the context of established health behavior theories. The first study is a systematic review of existing research on COVID-19 vaccine hesitancy using one or more health behavior theories as key components of the design or analysis. This study examined the types of theories that are most often used, how they are used, and where research gaps exist. The remaining two studies use data from the U.S. COVID-19 Trends and Impact Survey, a national cross-sectional survey. The second study investigates the association between recent feelings of anxiety or depression and vaccination intention, as well as between these feelings and identifying with specific vaccine hesitancy reasons. The third study examines vaccine hesitancy and barriers among those with chronic illness or disease, a particularly vulnerable population. Factor analysis was conducted using constructs from the Theory of Planned Behavior as a framework, and the results were used in a regression model to investigate the association between these underlying factors and vaccination intention. This research demonstrated the usefulness of the Theory of Planned Behavior, the Health Belief Model, and the 3 Cs Model in existing and future COVID-19 vaccine hesitancy research, as well as identified Protection Motivation Theory as a promising area for future research. Additionally, psychological states were demonstrated to be significantly associated with vaccine hesitancy, adjusting for demographic, socioeconomic, and time factors. Lastly, the Theory of Planned Behavior was found to be applicable to those unvaccinated and with chronic illness, as the construct factor scores developed were significantly associated with vaccine hesitancy (adjusting for the presence of specific chronic conditions and demographic, socioeconomic, and time factors). These associations were also consistently demonstrated in subgroup analyses of participants with specific chronic conditions.Item Social Determinants of Cardiovascular Disease Across the Life Course(2023) Ng, Amanda Erin; Dyer, Typhanye; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)According to data from the National Center for Health Statistics, cardiovascular disease is one of the leading causes of death in the United States, contributing to about 697,000 (or 1 in 5) deaths in 2020 alone. Given the public health burden of this disease, it is imperative that research identifies and continues to investigate population factors that may contribute to or alleviate this burden in the United States. The proposed study aimed to analyze such factors across the life course. Study 1 examined associations between an expanded set of Adverse Childhood Experiences (ACEs) and childhood obesity among 10-17 year olds using the National Survey of Children’s Health, as well as sex and age differences within these associations. Study 2 investigated high optimism as a modifier and mediator of the association between childhood socioeconomic disadvantage and CVD in midlife, using the Midlife in the United States Study, a U.S. prospective cohort. Study 3 examined temporal trends in the associations between adult socioeconomic status and CVD mortality using nationally-representative data from the 1997-2018 National Health Interview Survey.Item EXHALED BREATH AEROSOL TRANSMISSION OF ACUTE RESPIRATORY INFECTIONS(2023) Lai, Jianyu; Milton, Donald K; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Acute respiratory infections (ARIs), which usually appear in the form of common colds and influenza, as well as outbreak brought on by emerging viruses such as SARS-CoV-2, result in millions of deaths and hospitalizations each year. Aerosols being exhaled by infected population and inhaled by susceptible population has been identified as an important transmission route for ARIs; yet few studies have compared the viral load in exhaled breath aerosol (EBA) in naturally and experimentally infected cases, as well as among various infections. The specific aims of this dissertation were: 1) examine the comparability of EBA viral shedding between experimentally and a full range of natural ambulatory influenza cases; 2) compare seasonal coronavirus, influenza, SARS-CoV-2 Omicron, and other SARS-CoV-2 variants in terms of viral loads in exhaled breath aerosols; and 3) examine the relative efficacy of face masks, KN95, and N95 respirators as source control for SARS-CoV-2. We analyzed data from four studies that collected 30-minute fine (≤5 μm) and coarse (>5 μm) EBA samples using a Gesundheit-II sampler. Viral RNA load in EBA was quantified using real-time RT-PCR. Nasal inoculation of influenza virus A/Wisconsin/67/2005 showed lower EBA viral shedding compared to the natural influenza A H3 infections. Among the viruses studied, SARS-CoV-2 Omicron variants demonstrated the highest viral RNA loads in both EBA size fractions, emphasizing its superior spread capability via inhalation. Furthermore, while all masks and respirators showed significant reductions in viral RNA load in exhaled aerosols, the duckbill N95 respirators stood out, providing reductions of up to 99% and outperforming both surgical and cloth masks, and KN95 respirators. Given the evident transmission risk via inhalation for the studied viruses, measures such as masking and indoor air hygiene are crucial. The pronounced efficacy of N95 respirators highlights their importance in healthcare settings and places with vulnerable populations, especially during periods of heightened respiratory viral infections.Item RACIAL AND ETHNIC DISPARITIES OF BREAST CANCER RISK: THE ROLE OF INDIVIDUAL AND NEIGHBORHOOD-LEVEL CARDIOMETABOLIC FACTORS(2023) Ogbenna, Bethany Townsend; Dallal, Cher; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Background: Observed racial and ethnic disparities in breast cancer are complex, in part, due to biological and behavioral factors at the individual and neighborhood level. Cardiometabolic factors such as the use of cholesterol-lowering drugs and engaging in healthy lifestyle behaviors may reduce breast cancer risk, however, the current understanding of these factors among diverse racial and ethnic populations remains limited. Moreover, at the neighborhood-level, the extent to which neighborhood socioeconomic status (nSES) influences inflammatory profiles among racially and ethnically diverse populations remains unclear. Using data from the Multiethnic Cohort Study (MEC), this dissertation investigates cholesterol-lowering drug use (Aim I) and a Healthy Lifestyle Index (HLI) (Aim II) in relation to postmenopausal breast cancer risk by race and ethnicity; and, assesses associations between nSES and inflammatory biomarkers among adults (Aim III). Methods: Prospective cohort analyses were conducted among postmenopausal women who completed the third MEC follow-up questionnaire in 2003 (Aim 1, n=41,394) or the baseline questionnaire in 1993-1996 (Aim 2, n=65,561) and were followed until 2017 for invasive breast cancer diagnoses (n=1,681 and 4,555 cases, respectively). Multivariable adjusted hazard ratios [HR] and 95% confidence intervals [95% CI] were estimated using Cox proportional hazards regression. For Aim III, multivariable linear regression assessed cross-sectional associations between nSES and inflammatory serum biomarkers (adiponectin, leptin and C-reactive protein) among adults residing in California (n=6,919) and Hawaii (n=6,899) (2000-2017). Results: Cholesterol-lowering drug use (Aim 1) and duration was not associated with breast cancer risk among all women with no statistically significant heterogeneity in associations by race and ethnicity (p-interaction >0.05). In Aim 2 analyses, women with a higher HLI score (Tertile (T)) had a reduced risk of breast cancer (HRT3 vs T1: 0.76; 95% CI: 0.69, 0.84; HRT2 vs T1: 0.88; 95% CI: 0.79, 0.97) compared to women in the lowest HLI tertile with a significant dose-response observed (p-trend <0.01). Similar patterns were observed across all racial and ethnic groups of women. In California and Hawaii, individuals living in low nSES neighborhoods had higher serum levels of CRP (p-trend <0.001; p-trend = 0.02, respectively) and leptin (p-trend <0.001) while adiponectin levels were lower (p-trend <0.01; p-trend = 0.03, respectively) compared to individuals living in neighborhoods with high nSES. Additional adjustment for body mass index attenuated these associations (p-trend >0.05) (Aim III). Public Health Impact: Findings from this dissertation further support engaging in healthy lifestyle behaviors as a preventative strategy for breast cancer reduction among multiethnic populations of postmenopausal women whereas cholesterol-lowering drug use was not associated with reductions in risk. In addition, residing in low nSES neighborhoods was associated with less favorable inflammatory biomarkers levels.Item UNCOVERING THE HIDDEN POPULATION IN THE TRANSMISSION OF COVID-19: ASYMPTOMATIC CASES(2023) Yu, Weijun; Nguyen, Quynh C.; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This dissertation investigates the impact of international and local mobility of asymptomatic versus symptomatic COVID-19 cases on the pandemic in Hong Kong.The first manuscript analyzed empirical data from 11,775 confirmed COVID-19 cases in Hong Kong from January 2020 to April 2021, building a retrospective cohort. The results indicated that COVID-19 asymptomatic airport or flight crew were ten times more likely to have inbound air travel history than symptomatic airport or flight crew (adjusted RR=10.00, 95% CI: 4.00–25.00), and the median flight duration of asymptomatic cases was 4.6 person-hours shorter than that of symptomatic cases (p<0.01). The second manuscript presented a social network analysis study that build networks for the three peaks of COVID-19 diagnosis in Hong Kong. The results showed that asymptomatic cases were 1.33 times more likely to be presented in the inbound flight cabin or airport with other COVID-19 cases simultaneously than symptomatic cases (95%CI: 1.21-1.45) at the early stage of the pandemic. Additionally, the study found that network percolation simulation targeted attacks were more efficient than random failures in dismantling networks with a low level of connectedness. The third manuscript used geocoded COVID-19 cases’ travel records in Hong Kong to conduct a spatial analysis study. The findings indicated that asymptomatic cases visited locations mostly clustered in the southern part of Hong Kong, while symptomatic cases visited locations mostly clustered in the middle and southern parts of Hong Kong. This study also found that Geographically Weighted Regression models performed better among symptomatic cases than asymptomatic cases, and median local travel time was higher (p<0.01) among asymptomatic (68.09 person-minutes) than symptomatic cases (59.46 person-minutes) based on 19,568 Origin-Destination Cost Matrix least-cost paths. Overall, this dissertation highlights the importance of promoting public health prevention strategies to contain future infectious disease pandemics at the early stage, regardless of the presence of symptoms. Moreover, it suggests that travel restriction may not be effective in dismantling networks with a low-level of connectedness. Local health authorities and policymakers should tailor detection and containment strategies based on spatial variability in different areas.Item Understanding the Risk of Drug Overdose and Alcohol-Induced Deaths Among Adults with Different Types of Disabilities(2023) Aram, Jonathan; Dallal, Cher M; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Background: Disability is associated with drug and alcohol morbidity and mortality, which have reached high levels in recent years. Previous disability studies often combine all disabilities into a single category or focus on a single type of limitation. This dissertation characterizes different types of disabilities among U.S. adults and assesses associations with drug and alcohol morbidity and mortality. Methods: Using the 2018-2019 National Survey on Drug Use and Health (NSDUH, Aim 1), a nationally representative cross-sectional survey (n=83,485), different individual disabilities and co-occurring disabilities were identified. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations between disability type and prevalence of drug and alcohol use disorders. Disabilities were also characterized within the Mortality Disparities in American Communities Study (Aims 2 and 3), a nationally-representative prospective cohort with baseline data collected in 2008 and mortality follow-up through 2019 (n=3,324,000). Multivariable Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHRs) and CIs for associations between disability type and drug overdose death (OD, Aim 2) and alcohol-induced death (AID, Aim 3). Results: Within the NSDUH analysis, adults with cognitive disability had increased odds of drug (aOR=3.3; 95% CI=2.9–3.8), and alcohol use disorder (aOR=2.3; 95% CI=2.0–2.6), compared to adults without disability. Positive associations of lesser magnitude were observed between hearing/seeing and ambulatory disabilities and drug use disorder. In MDAC analyses, OD risk was elevated among adults with cognitive (aHR=2.6; 95% CI=2.4–2.9), ambulatory (aHR=2.8; 95% CI=2.6–3.1), ambulatory and hearing/seeing (aHR=2.5; 95% CI=2.0–3.1), and hearing/seeing disability (aHR=1.6; 95% CI=1.4–1.9), compared to adults without disability. The risk of AID was elevated for adults with co-occurring ambulatory and hearing/seeing disability (aHR=1.8; 95% CI=1.5–2.2), ambulatory disability only (aHR=1.5; 95% CI=1.3–1.7), and hearing/seeing disability only (aHR=1.2; 95% CI=1.0–1.4). Conclusions: The examination of specific disability categories reveals unique associations that are not apparent when all disabilities are combined. These findings can be used to improve access to recovery support services. Expansion of educational and occupational opportunities for adults with disabilities should be considered as strategies to reduce drug and alcohol morbidity and mortality.Item Effects of Tamoxifen Therapy on Breast Carcinogenesis: Epidemiological Associations and Biomechanisms of Action(2022) Ghosh, Rajrupa; Dallal, Cher; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Background: Tamoxifen, a key chemopreventive and adjuvant endocrine therapy (ET) for breast cancer, is suggested to alter breast cancer risk factors including circulating hormones (estrogen and insulin-like growth factors (IGFs)) and breast density. However, the biological underpinnings of tamoxifen’s effect on these factors remain unclear. This dissertation evaluated effects of tamoxifen on estrogen metabolites (EMs), explored associations between circulating IGFs (IGF-I and IGFBP-3) and volume average sound speed measures (VASS) of breast density, and synthesized evidence from real-world studies to meta-analyze adjuvant ET in relation to contralateral breast cancer (CBC) risk. Methods: Within the Ultrasound Study of Tamoxifen, serial serum samples collected prior to and 12 months after tamoxifen treatment were used to assess longitudinal changes (paired t-tests) in 15 circulating EMs among postmenopausal women (n=23) (Aim 1), and changes in IGFs and VASS (n=53) (Aim 2). Multivariable linear regression examined associations between metabolites of tamoxifen and estrogen among pre- (n=33) and postmenopausal women (n=27) (Aim 1) and concomitant changes in IGFs and VASS (n=53) (Aim 2), 12 months after treatment initiation. In Aim 3, a random effects meta-analysis of observational studies (n=17, 287,576 participants) estimated relative risks (RR) and 95% confidence intervals (CI) for associations between ET and CBC risk among primary breast cancer patients overall, by menopausal status and CBC estrogen receptor (ER)-subtype. Results: Circulating 2-OH and 16-OH pathway EMs, IGF-I, and IGF-I:IGFBP-3 decreased 12 months after tamoxifen initiation (p <0.05; Aims 1 and 2). No associations were observed between concomitant changes in IGFs and VASS among tamoxifen-treated patients (Aim 2). In meta-analyses (Aim 3), endocrine therapy was associated with reduced CBC risk (RR: 0.62, 95% CI: 0.53, 0.73), with a greater reduction observed among premenopausal (RR: 0.58, 95% CI: 0.43, 0.78) versus postmenopausal women (RR: 0.72, 95% CI: 0.60, 0.87). Endocrine therapy reduced the risk of ER-positive (RR: 0.55, 95% CI: 0.43, 0.70) but not ER-negative CBC. Conclusion: The tamoxifen mediated decline of circulating 2-OH, 16-OH and IGF-I provides etiologic insight into the biomechanisms of tamoxifen on breast carcinogenesis. Meta-analyses of observational studies further support a chemopreventive role of endocrine therapy on CBC risk, particularly, ER-positive CBC.Item Intersectional stigma, self-efficacy, depression, and resilience: a Rasch analysis(2022) Reuben, Jacqueline; Liu, Hongjie; Turpin, Rodman; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Background: Black men who have sex with men (BMSM) are disproportionally affected by negative health outcomes associated with stigma related to both their racial and sexual minority status. Foundational to understanding stigma is the ability to correctly measure this latent construct. The Rasch model is a probabilistic model for analyzing categorical data that was developed to improve the measurement of latent traits. This study, grounded in intersectional minority stress theory, reviewed the application of Rasch analysis in the HIV/AIDS literature (Aim 1) and used the Rasch model to calibrate person measures to assess the interrelationships among internalized stigma, resilience, self-efficacy, and psychologic well-being among BMSM (Aims 2 and 3). Methods: For Aim 1, we conducted a systematic review of the literature following PRISMA guidelines. Aims 2 and 3 used data from a cross-sectional online survey of 151 HIV-negative BMSM in 2020. For Aim 2, we conducted Rasch analysis to assess the psychometric properties of the internalized racism (IR), internalized homophobia (IH), self-efficacy, and resilience scales. For Aim 3, we used linear regression and path analysis of the Rasch-calibrated person measures to examine the mediating and modifying effects of self-efficacy and resilience on the relationship between intersectional stigma and depressive symptoms. Results: For Aim 1, after screening 183 articles, 45 articles were included in the analysis. Strengths and weaknesses of using the Rasch approach were summarized. For Aim 2, the final IR scale had a person reliability and separation of 0.91 and 3.13, respectively, and an item reliability and separation of 0.94 and 4.01, respectively. The final IH scale had a person reliability and separation of 0.88 and 2.72, respectively, and an item reliability and separation of 0.79 and 1.95, respectively. For Aim 3, IR (β=0.296, 95% CI [0.133, 0.458]) and IH (β=0.414, 95% CI [0.204,0.623]) were independently and positively associated with depression in multivariable models controlling for age, income, and relationship status. Resilience and self-efficacy modified the relationship between IH and depression (βIHxRES=-0.034, 95% CI [-0.060, -0.008] and βIHxSE=-.056, 95% CI [-0.113, 0.00], respectively), but there was no evidence of effect modification by resilience or self-efficacy on the association between IR and depression. Public health implications: Our findings suggest that interventions targeting multiply marginalized groups such as BMSM that address co-occurring forms of stigma and foster positive self-evaluation and coping skills may reduce the negative consequences of internalized stigma on mental health outcomes.Item The effects of HIV criminalization laws (and their enforcement) on HIV risk among Black and Hispanic populations(2022) Keralis, Jessica Maciel; Nguyen, Quynh C; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Background: In the U.S., 25 states have laws that explicitly criminalize the transmission or exposure of HIV. This study, grounded in Nancy Krieger's ecosocial theory, estimated the association between HIV criminalization laws and state- (Aim 1) and county-level (Aim 2) HIV incidence rates, as well as individual HIV testing history (Aim 3), and assessed effect modification by overpolicing, using incarceration rates as a proxy. Methods: The study uses data from state- and county-level HIV incidence data from AIDSVu (2010-2019), incarceration data from the Vera Institute of Justice (2010-2018), and HIV testing data from BRFSS (2016-2019). For Aim 1, a longitudinal analysis was conducted using multivariate marginal Poisson GEE models to estimate rate ratios. For Aim 2, count-rate hierarchical (multilevel) models were fitted to estimate rate ratios. For Aim 3, logistic regression models were fitted to estimate odds ratios. Results: The presence of a state HIV testing law was associated with a higher state HIV incidence in the general and Hispanic populations (aRR=1.48 and 1.68, respectively), but higher incarceration at the state level did not significantly modify the relationship between the law and HIV incidence. At the county level, being in a state with an HIV-specific criminalization statute was associated with a higher county-wide HIV incidence rate for all three populations (aRR=1.14, 1.30, and 1.32 for the general, Black, and Hispanic populations, respectively). Unlike the state-level analysis, this association was attenuated by a higher jailed population rate for the general and Black populations. The effect modification was statistically significant for the general population (p=0.01) and marginally significant for the Black population (p=0.06). Finally, the presence of a state HIV testing law (aOR=1.06) was associated with a greater likelihood of HIV testing history in the general population. However, in HIV criminalization states, heavier policing negatively modified the effect of the law on the likelihood of having ever received an HIV test (p<0.01). Public health implications: This study contributes to a gap in the literature by using recent data to estimate the association of HIV criminalization laws and their enforcement with HIV incidence rates and HIV testing behavior.