INTRODUCTION: Cardiovascular disease (CVD) is a leading cause of death in the United States. It can lead to hospitalization, disability, mortality and decreased quality of life. Abnormal hemoglobin concentration (anemia or higher than normal level) has been proposed as a potential risk factor for CVD. However, it has not been tested in general postmenopausal women using large perspective study method. The overall objective of this dissertation is to examine the association between abnormal hemoglobin concentration, left ventricular hypertrophy (LVH), and cardiovascular outcomes in postmenopausal women. METHODS: This dissertation unitized data from the Women's Health Initiative (WHI) cohort. Hemoglobin concentrations were classified into several categories: normal (12g/dl ≤ hemoglobin ≤ 15g/dl), mild anemia (hemoglobin < 12g/dl), moderate anemia (hemoglobin < 11g/dl), severe anemia (hemoglobin < 10.5g/dl), and extremely high hemoglobin (EHH) (hemoglobin > 15g/dl). Three associations were assessed. Hemoglobin concentration and subsequent cardiovascular events were tested in the WHI participants without prior CVD (n=123,465). The association between hemoglobin concentration and cardiovascular death was tested in the WHI participants with prior CVD (n=26,929). The last study, testing the association between hemoglobin concentration and LVH, were assessed cross-sectionally in the WHI clinical trials which had electrocardiographic (ECG) data (n=57,551). RESULTS: In women without prior CVD, both anemia and EHH was associated with an increased risk of cardiovascular events. The association varied by age groups, and EHH associated cardiovascular risk decreased with age. In women with prior CVD, risk of cardiovascular death significantly increased by 48%, 90% and 32% in mild anemia, moderate/severe anemia, and EHH group respectively compared to normal group. In the WHI participants who had ECG data, odds ratios of LVH were 1.13 (95% CI: 0.90-1.41), 1.35 (95% CI: 0.76-2.40), and 1.32 (95% CI: 0.76-2.40) for mild anemia, moderate/severe anemia, and EHH group respectively compared to normal group. CONCLUSION: These studies constantly demonstrated a U-shaped association between hemoglobin concentration and cardiovascular risk in the postmenopausal women. It suggests that the association of hemoglobin concentration and incidence of CVD was modified by age. Additional research is needed to determine whether there is a cause-and-effect relationship between hemoglobin concentration and LVH.

Background: Although cigarette smoking is decreasing in the US and among college students, tobacco use remains a major public health problem. Specific socioecological gaps in the literature related to college tobacco use exist including: trends of tobacco use, combinations of polysubstance use, and availability of tobacco products around college campuses. Objectives: The main goal of this research was the understand interrelationships that exist within a socioecological framework of college tobacco use. Specifically, this project aims to: 1) examine trends of tobacco and polytobacco use by gender and associations of polytobacco use and perceived peer tobacco use, 2) examine specific combinations of polysubstance use and how the resulting profiles of use differ by gender, and 3) evaluate tobacco retailer density around college campuses and in neighborhoods of Richmond, VA. Methods: Two chapters of this project use data from the National College Health Assessment II from 2008-2015. The third chapter uses data collected from electronic cigarette brand websites to geospatially examine tobacco retailers in the Richmond Virginia Metropolitan Statistical Area. Various statistical analyses were utilized to complete each project including linear, logistic, and negative binomial regression, latent class and confirmatory factor analysis, and spatial analysis. Results: Trends of some tobacco products among US college students declined while others remained stable from 2008-2015. Nearly 1 in 4 college students used a tobacco product and nearly 1 in 10 were polytobacco users. Alcohol and marijuana use remained stable. Specific classes of polysubstance users were found to exist between males and females, in addition to sociodemographic and institutional associations with polysubstance use by gender. College campuses in the Richmond area were found to have a substantial number of tobacco retailers and retailer density was higher in low socioeconomic status neighborhoods. Conclusions: The findings from the three different studies fill extensive gaps in the literature related to trends of college tobacco use, differences in classes of polyuse by gender, and availability of tobacco around college campuses. Overall, while tobacco use is declining, there are still a substantial proportion of college students who use tobacco and other substances and products appear to be readily available.

It is plausible that calcium intake and the calcium: magnesium (Ca:Mg) intake ratio play an essential role in the development of colorectal cancer. The first project of this dissertation was to determine the role of calcium intake and its interaction with Ca:Mg intake ratio in risks of incident adenoma, metachronous adenoma, and colorectal cancer using the data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). The study included incident colorectal adenoma (1,147 cases), metachronous adenoma (855 cases) and incident colorectal cancer (697 and 578 cases in intervention and control arms, respectively) among 108,563 PLCO participants aged 55 to 74 years. Compared to low calcium intake (<600 mg/day), higher intakes of calcium were associated with suggestive reduced risk of advanced and/or synchronous adenomas and significantly reduced risk of colorectal cancer, especially for distal colorectal cancer. No such evidence was found for incident colorectal adenoma. The inverse association between calcium intake and advanced and/or synchronous adenoma, were primarily appeared in participants with Ca:Mg ratios ranging from 1.7 to 2.5. In addition, the significant association between calcium intake and risk of incident distal colorectal cancer appeared to be primarily in the control arm without regular endoscopy. The second and third projects of this dissertation were to examin whether reducing the Ca:Mg intake ratio through magnesium supplementation change levels of lipid biomarkers and uric acid among participants with Ca:Mg intake ratio ⥠2.6 in the Personalized Prevention of Colorectal Cancer Trial (PPCCT). Among 150 participants in the PPCCT study who finished the trial, overall, magnesium treatment did not significantly affect lipid profile including low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-c), triglycerides, total cholesterol, and uric acid. Among participants with long-term high Ca:Mg ratio, magnesium supplementation led to a statistically significant increase of HDL-c level by 5 mg/dl. This study provides additional evidence to understand the modifying effect of Ca:Mg intake ratios on the association between calcium intake and risk of colorectal cancer development at various stages.

The primary objective of this research project is to evaluate the protective efficacy, epidemiological and economic impacts of voluntary medical male circumcision (VMMC) as an intervention strategy to reduce HIV infection among men who have sex with men (MSM) population in China. Therefore, (1) we conducted a systematic review and meta-analysis to evaluate the protective efficacy of the association between male circumcision and HIV infection among MSM with a series of sensitivity analyses. Our findings suggested a statistically significant protective efficacy of VMMC among MSM (aOR=0.93, 95%=0.88,0.99), especially among MSM with moderate risk profiles; (2) we employed a transmission model to assess the epidemiological impact of VMMC by projecting numbers of new HIV cases for the next decade among MSM in Beijing, China. Our model suggested even at 15% VMMC annual uptake rate, the reduction in new infection is substantial; and (3) we assessed the economic impact of VMMC program in China by a series of âbudget-impactâ analyses. The VMMC would be an effective and economic intervention strategy to curb the HIV epidemic in China.

It has been widely shown that intravenous drug use (IVDU) is a major risk factor for Hepatitis C Virus (HCV), and Hepatitis C remains highly prevalent among homeless populations. More data is needed to demonstrate the effectiveness of linkage to care and treatment programs within these high risk populations. Determining the social and clinical risk factors associated with lower rates of positive HCV clinical outcomes such as linkage and treatment can have a significant impact on patient outcomes and public health program success. A prospective cohort of 1254 subjects was used for these analyses. Log binomial regression models were created for the analysis of both homelessness and whether the patient has ever injected drugs (ever-IVDU) separately for their associations with linkage to HCV care. The cohort was 68% male and 32% female, with median age of 44 years old (range 18-90 years old). Thirty-five percent of the study population was inside the “baby boomer” birth cohort (born 1945-1965) which is considered to be a particularly high risk population. Four percent of the population was co-infected with Hepatitis B Virus and 6% were co-infected with HIV. Sixty-two percent of the cohort reported homelessness, and 78% had ever used IV drugs. Homeless individuals had an adjusted RR of 0.82 (95% CI: 0.70-0.91) and patients having ever used IV drugs had an adjusted RR of 1.06 (95% CI: 0.94–1.19) for the outcome of HCV linkage to care. The results of this study showed that homeless individuals had an 18% decreased risk of becoming linked to care compared to those that are not homeless, while ever- IVDU showed no significant association with linkage to care after controlling for confounding. With Hepatitis C being so prevalent among homeless populations, these results are especially helpful in informing linkage to care programs. Understanding the major barriers to care that these patients face is crucial to designing linkage and navigation programs that will successfully engage and benefit these patients.

Numerous studies have linked inadequate gestational weight gain to preterm birth and small-for-gestational age births (SGA) and excessive gestational weight gain to large-for-gestational age births, but gaps remain in our understanding of these relationships. Study 1 evaluated predictors and outcomes associated with area under the gestational weight gain curve. Compared to the middle quintile, the highest quintile of accumulated pound-days was associated with a decreased hazard of spontaneous preterm birth [Hazard Ratio (HR): 0.54, 95% Confidence Interval (CI) 0.30, 0.96)] and small-for-gestational age (SGA) births (HR 0.52, 95% CI 0.36, 0.76) overall and an increased hazard of LGA births among normal and underweight women (HR 3.78, 95% CI 1.76, 8.13). Study 2 evaluated potential predictors of high and low gestational weight gain using the INTERGROWTH 21st standards among pregnant women in Dar es Salaam, Tanzania and examined the relationship between gestational weight gain and preterm birth, perinatal death, small-for-gestational age births, and large-for-gestational age births. Weight gain below the 3rd percentile was associated with increased hazards of perinatal death [Hazard Ratio (HR): 1.94, 95% Confidence Interval (CI) 1.01, 3.73)] and small-for-gestational age (SGA) births (HR 1.51, 95% CI 1.02, 2.24), and a decreased hazard of preterm birth (HR 0.65, 95% CI 0.48, 0.88). Weight gain above the 97th percentile showed a trend toward an increased hazard of large-for-gestational age births (HR 1.77, 95% CI 0.96, 3.25). Study 3 assessed the accuracy of interpolated weight values obtained from regression models when compared to measured weight values at 28 (n=764) and 40 (n=358) weeks of gestation using data from the LIFECODES cohort at Brigham and Women’s Hospital. Mean differences in pounds between observed and estimated weights derived from the 28-week linear model (0.18 (SD 6.92), Bland Altman limits of agreement = -13.66–14.01) and 40-week linear models (-0.40 (5.43), limits of agreement -11.26–10.23), while weight values derived from the 40-week spline model underestimated observed weights (mean difference -2.50 (SD 6.91), limits of agreement 16.31–11.30 and -3.38 (SD 5.44), limits of agreement -14.26–7.49, respectively). Estimated weights derived from all models showed near perfect correlation with observed values (r=0.97–0.99).

Throughout the past several years, there has been growing interest in folic acid as a crucial micronutrient that has several beneficial health outcomes. Given folic acid's crucial role in DNA synthesis and methylation, it is involved in several processes, especially during development. Although folic acid has been studied previously with several disease processes such as neural tube defects, different types of cancer and even Alzheimer's disease, specific attention has not been given to folic acid and reproductive health and other pregnancy outcomes such as implantation, embryogenesis and live birth. This thesis will examine the specific effects that folic acid could have in maintaining the reproductive health in women and men as well. The conclusion was reached that folic acid plays a critical role in several phases of reproductive health including maintenance of reproductive hormone levels in woman, protection against anovulation and spontaneous abortions as well improving sperm quality in males. Taken together, folic acid could be an inexpensive, convenient supplement for maintaining reproductive health as well as for couples who are attempting to begin and maintain a healthy pregnancy.

Women of African ancestry (AA) experience a greater burden from breast cancer and type 2 diabetes compared to women of European ancestry. Some of the racial disparities observed for these diseases may be explained by AA-specific genetic risk variants. The projects conducted here sought to discover risk variants in AA women for overall and subtype-specific breast cancer and for type 2 diabetes using pathway- and gene-based analytic approaches. Project 1 evaluated 170,812 mostly rare variants across the exome in 3629 breast cancer cases (1093 estrogen receptor negative (ER-), 1968 ER+, 568 ER unknown) and 4658 controls from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. Gene-based analyses found ER- associations with PDE4D (previously identified in GWAS) and FBXL22 (novel), based on very small counts at extremely rare SNPs. Project 2 evaluated common SNPs in 308 genes in hormone pathways using 3663 breast cancer cases (1098 ER-, 1983 ER+, 582 ER unknown) and 4687 controls from AMBER. Gene-based and single SNP analyses identified eight genes (CALM2, CETP, NR0B1, IGF2R, CYP1B1, PGR, MAPK3, and MAP3K1) that contained common variants associated with overall or subtype-specific breast cancer after gene-level correction for multiple testing. Project 3 evaluated common SNPs in 69 genes involved in the Wnt pathway using 2632 type 2 diabetes cases and 2596 controls from the Black Women’s Health Study. Gene-based and single SNP analyses were run, and an association was observed between the PSMD2 gene region and type 2 diabetes. Association data on a subset of the top PSMD2 SNPs were available from a large, independent AA sample; associations were in the same direction, but weak and not statistically significant. We also identified a TCF7L2 SNP that may represent a novel, independent association signal seen only in AA populations. Many of the SNPs identified in the present research are more common in AA populations, possibly explaining their lack of discovery by European ancestry genome-wide association studies. Replication of the associations we observed using independent AA samples is necessary. Future studies should consider the entire gene regions identified in our research rather than focusing solely on the specific variants highlighted.

The purpose of this study was to evaluate the proportion of women who reported perception of medications as a risk for birth defects, whether perceptions have changed over time, and identify socioeconomic and medical factors that are independent predictors of perception of medication risk. The information gained may be useful in developing strategies for the risk management of known teratogens and enhancing the appropriate use of medications known to be safe. From 1976 to 2015, 51,413 women from the Slone Epidemiology Center Birth Defect Study (Slone BDS) were interviewed about whether they were aware of any medication or other substance that might cause birth defects, and about sociodemographic and medical factors. This analysis focused on those participants who reported one or more medication (or vitamin) as a risk factor for birth defects. The results demonstrated a general trend towards fewer women perceiving medication risk over the past four decades. The proportions of women who reported perception were higher for the following variables: older maternal age, white race, higher educational levels, previous pregnancy of a child with reported birth defects, daily medication use during pregnancy, wanted pregnancy, and alcohol use during pregnancy. The study does not support the likelihood of recall bias in women who gave birth to a baby with a birth defect, an important concern in epidemiological studies of birth defects. Misconception of risk was identified; of the top ten medications reported as potentially teratogenic, only three (thalidomide, isotretinoin, and diethylstilbestrol) are established teratogens. Overestimation of risk could potentially impact a woman’s decision to continue a pregnancy or cause unnecessary anxiety when using a medication that is needed during pregnancy. It has previously been shown that counseling pregnant woman can decrease the misperception of teratogenic risk from medications used for nausea and vomiting of pregnancy. Other researchers have suggested that greater use of drug information centers, such as the Norwegian network of drug information centers (RELIS), may help guide pregnant women and prescribing providers to improve teratogenic risk management.

Healthcare-associated infections (HAI) caused by multi-drug resistant organisms (MDRO) are an important patient safety concern resulting in a substantial financial and clinical burden. This dissertation aims to contribute to the evidence base on institutional and patient level factors that predict multi-drug resistant infections in the hospital setting. In the first chapter, I review the evidence base on patient-level risk factors for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI), system-level factors associated with implementation of infection control policies and MDRO rates, and the current knowledge on the use of infection control policies on the national level. In the second chapter, I use data from a national cross-sectional study to describe the range of MDRO screening and infection control policies in U.S. hospitals and identify predictors of their presence and implementation. In the third chapter, using data from a cross-sectional study of California hospitals, I assess the association between the presence and implementation of infection control policies for MDRO infections and rates of BSI caused by MRSA or vancomycin-resistant Enterococcus and infections caused by Clostridium difficile. Next, I identify risk factors for healthcare-associated MRSA BSI in a nested case control study using two sets of controls. In the last chapter, I conclude by summarizing the findings of these three studies.