- ItemRACIAL 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.
- ItemUNCOVERING 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.
- ItemUnderstanding 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.
- ItemEffects 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.
- ItemIntersectional 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.