Vector-borne diseases are a resurgent focus in public health. As concern about climate change mounts, the close relationship between these diseases and the environment has garnered growing attention. This dissertation examines the relationship between environment and vector-borne disease in both human and veterinary medical contexts and on both a local and national scale. The first study investigated using a novel Internet-based surveillance system for risk mapping of West Nile Virus (WNV) in the contiguous United States from 2007-2014, with meteorological, demographic, and land use variables as predictors. The study found that annual average temperature, minimum temperature, precipitation, and human population density were predictive of WNV reports, but that the novel surveillance data appeared to have systematic gaps that impair the utility of the model. However, the results may help to guide improvements in novel surveillance systems. The second study used the logistic regression model developed in the first study to predict the risk of WNV in the contiguous United States in 2050 and 2070 under four projected climate scenarios. The study found that Southern California is likely to remain the area of greatest risk under all scenarios and that risk would be expected to increase across much of the West under the scenario of uncontrolled carbon dioxide emissions. The results of this study may inform development of more sophisticated models and may help to direct public health resources to areas of greatest impact. The third study investigated the relationship between cases of canine Lyme nephritis and precipitation in the months prior to diagnosis. Precipitation three months prior to diagnosis was found to be associated with the development of Lyme nephritis (hazard ratio for 1 inch/month 1.125, 95% confidence interval 1.009 – 1.254). This finding may improve diagnostic accuracy for dogs with protein-losing nephropathies and may guide studies of additional risk factors.

Maltreated youth have higher rates of school dropout than their non-maltreated peers. School connectedness is a modifiable predictor of school success. We hypothesized maltreated youth’s school connectedness (supportive relationships with adults at school and participation in school clubs) would be positively associated with high school graduation. We included youth with at least one Child Protective Services (CPS) report by age twelve from Longitudinal Studies of Child Abuse and Neglect, a prospective cohort study. Participation in extracurricular activities and adult relationships reported at age 16, high school graduation/General Education Development (GED) status reported at age 18, and demographics were provided by youth and caregivers. Maltreatment data were coded from CPS records. The outcome was graduation/receipt of GED. Multivariable logistic regressions examined the association between school connectedness and graduation/receipt of GED, controlling for confounders. In our sample of 318 maltreated youth, 73.3% graduated. School club was the only activity with a statistically significant association with graduation in bivariate analysis. Supportive relationships were not significantly associated with graduation, though only 10.7% of maltreated youth identified supportive relationships with adults at school. Maltreated youth who participated in school clubs had 2.54 times the odds of graduating, adjusted for study site, gender, poverty status, caregiver high school graduation status, and age at first CPS report (95% CI: [1.02, 6.33]). Few maltreated youth reported relationships with adults at school, and additional efforts may be needed to support these vulnerable youth. School club participation may represent an opportunity to modify maltreated youth’s risk for school dropout. / 2019-06-09T00:00:00Z

Streptococcus pneumoniae colonization is the nasopharynx is common in young children. Colonization of S. pneumoniae is a necessary precursor for invasive pneumococcal disease (IPD), which is a major cause of morbidity and mortality among children less than five years of age globally. Co-morbidities such as asthma have been identified as risk factors for IPD but little is known about why. Children with co-morbidities have a higher likelihood of progressing to IPD because they are colonized at higher rates or because their immune systems respond differently than children without co-morbidities. In addition, vaccination was introduced in 2010 to help decrease pneumococcal colonization rates from the 13 most common serotypes. We used data from the pediatric primary care clinic at Boston Medical Center to study the relationship between asthma/wheeze and S. pneumoniae colonization among children under the age of five years. Information about colonization serotype distribution was also assessed in this study. Data was accessed from 3098 children from 4–59 months old visiting the pediatric primary care clinic at Boston Medical Center from July 2010 to March 2014. In multivariable logistic regression models, the odds of colonization increased 80% (OR 1.80, 95% CI 1.2, 2.6) in children with asthma/wheeze under 24 months old. Adjustment for presence of URTI or recent exposure to antibiotics slightly mitigates this relationship. Children with clinically diagnosed asthma/wheeze have 80% increased odds of being colonized than children without asthma/wheeze.

BACKGROUND: Urine drug testing (UDT) is recommended to monitor primary care patients treated for opioid use disorder with buprenorphine. Whether UDT data contributes clinically useful information beyond patient self-report of drug use has received minimal attention. It is unclear whether differences between patient self-report and UDT results varies with time in treatment. OBJECTIVES: To estimate concordance between self-report and UDT results and evaluate if discordant results are associated with time in treatment. METHODS: Retrospective review of electronic medical records of patients enrolled in the Office Based Opioid Treatment program at Boston Medical Center between January 2011–April 2013. Typically, patients submit a urine sample for UDT at the beginning of a clinical visit and are subsequently asked about recent cocaine and opioid use which is documented in the electronic medical record. We compared UDT results to patient self-report of cocaine and opioid use. RESULTS: Of 1,755 UDT from 130 patients, 4% (78/1755) were positive for cocaine and 10% (157/1563) for opioids other than buprenorphine. At visits with a cocaine positive UDT, 76% of patients (59/78) did not disclose cocaine use. At visits with an opioid positive UDT, 57% of patients (89/157) did not disclose opioid use. The odds of having a positive UDT for either cocaine or opioids with no disclosure of use decreased over a year of treatment. CONCLUSION: In a sample of primary care patients with opioid use disorder treated with buprenorphine, fewer than 10% of UDTs were positive for cocaine or opioids, and in these instances patient self-reported use of cocaine or opioids less than half the time. As duration of treatment increased, patients were more likely to disclose use. Urine drug testing contributes new and useful information for clinical consideration of the optimal care of patients with drug use disorders; how best to collect and utilize this information merits further study.

<p> Vaccinations are among the greatest accomplishments of public health. However, many parents are choosing not to vaccinate. The purpose of this study was to explore the association between social media influence and parents&rsquo; decisions to vaccinate their children. The health belief model indicates that individuals&rsquo; likelihood of engaging in a health-related behavior is determined by their perceptions of susceptibility, severity, benefits, and barriers. The research questions addressed whether there is an association between parents&rsquo; perception of their children&rsquo;s disease susceptibility and their decisions about vaccination, and whether there is an association between exposure to messaging from social media and parents&rsquo; decision to vaccinate. A quantitative, cross-sectional research design was used. The primary dependent variable was vaccination choices, and the primary independent variable was exposure to information about vaccination through social media. Data were gathered through a questionnaire administered to 269 White parents residing in Illinois with their own children between the ages of 0 and 18 years living with them. Binomial logistic regression showed that there was not a statistically significant relationship between parents&rsquo; perception of disease susceptibility and vaccination choice or between parents&rsquo; vaccination choice and exposure to online antivaccine advertisements. These study findings help in defining an overall picture of vaccine hesitancy in the United States. By focusing on the predictors of this behavior, it may be possible to implement interventions to combat the antivaccine movement with the goal of increasing vaccine compliance among parents.</p><p>

<p> Tocilizumab is a humanized monoclonal anti-body against the interleukin-6 receptor and is effective in the treatment of rheumatoid arthritis (RA). Multiple studies have observed unfavorable changes in the lipid profile of tocilizumab-treated RA patients. Few studies have compared the cardiovascular disease (CVD) risk associated with tocilizumab to other biologic disease-modifying antirheumatic drugs (bDMARDS). Due to limitations in existing studies, the real-world association of tocilizumab with CVD risk remains uncertain. </p><p> We conducted a retrospective cohort study using 2006&ndash;2015 Medicare and MarketScan claims data to assess the comparative effect of tocilizumab on CVD risk. Medicare claims data provide a unique opportunity to estimate disease burden and conduct comparative effectiveness studies with much larger sample sizes than cohorts, which require primary data collection. However, Medicare claims data lack information on cause of death. To address this limitation, we developed claims-based algorithms for identifying fatal CVD in Medicare claims data using The Reasons for Geographic and Racial Difference in Stroke (REGARDS) data linked to Medicare claims. CVD events iv and cause of death in the REGARDS study were adjudicated by two experts. Our algorithm can identify fatal CVD events with high sensitivity and specificity. </p><p> Our study confirmed that tocilizumab was not associated with increased or decreased CVD risk compared to etanercept: the hazard ratio for tocilizumab compared to etanercept was 0.91 (95%CI: 0.66, 1.25). However, unlike the clinical trial, which enrolled only high-risk patients, we extended this finding to &ldquo;low CVD risk&rdquo; RA patients. We also showed that tocilizumab was not associated with increased or decreased CVD risk compared to abatacept or rituximab. We further showed that tocilizumab was associated with reduced CVD risk when compared to a pooled TNFi group. This is most likely due to slightly increased CVD risk associated with infliximab. </p><p> We also conducted a retrospective cohort study using Medicare claims data to assess the effect of methotrexate on CVD risk among bDMARDS users and found that methotrexate was associated with an overall 27% (95%CI: 18&ndash;35%) reduction in CVD risk. The hazard ratio for tocilizumab concomitantly with methotrexate compared to tocilizumab only was 0.66 (95%CI: 0.40&ndash;1.09). </p><p>

Although certain opioid analgesics have shown immunosuppressive properties in animal experiments, the clinical implications of prescription opioid use on the risk of serious infection among humans are unknown. We conducted a series of epidemiological studies to test the hypothesis that prescription opioid use is an independent risk factor for serious infections and that the association differs across opioid type and dose. In a nested-case control study conducted among subjects enrolled in Tennessee Medicaid (TennCare), we showed that opioid use was strongly and consistently associated with an increased risk of laboratory-confirmed invasive pneumococcal disease (IPD). The observed association was strongest for long-acting and high potency formulations, and for high dose opioids. As laboratory-confirmed IPDs are relatively rare, a separate study was conducted to assess the performance of coding algorithms for identifying hospitalizations for serious infections from TennCare administrative data. Using medical chart reviews as reference, we demonstrated that coded algorithms had a high positive predictive value for identifying true infections, supporting their use in epidemiological studies. Finally, we assembled a retrospective cohort of adults enrolled in TennCare who initiated use of long-acting opioids to compare the risk of serious infection among subjects initiating opioids with previously reported immunosuppressive properties compared to those initiating opioids without known immunosuppressive properties. Hospitalizations for serious infection were identified using our previously validated coding algorithms. The incidence of serious infections was significantly higher among users of opioids with previously described immunosuppressive properties, compared with users of opioids without immunosuppressive properties. These findings complement previous experimental evidence and support the hypothesis that opioid use is a novel, clinically important risk factor for serious infections.

Helicobacter pylori is the major causative agent of numerous gastric disorders including gastric cancer, the second leading cause of cancer mortality worldwide. While over half of the world’s population are infected with the bacterium, only a small fraction of these individuals develop severe health outcomes. This acknowledgement suggests other factors, including host and pathogen genetic variation, genetic interactions, and environmental factors are likely to play an important role in the development of gastric disease after H. pylori infection. Recent research has sought to fill these gaps in knowledge, with one such study concluding that coevolution between humans and H. pylori is a likely modifier of disease risk. To further explore the underlying contributors to gastric disorders, we examined the association between the severity of gastric lesions, quantified through histopathologic scores, and patterns of genomic variation in matched human and H. pylori samples. Analyzed data were obtained from a previous study, with study participants having been recruited from two distinct Colombian populations possessing significantly different incidences of gastric cancer but similar H. pylori infection prevalence. Estimates of human ancestry, polymorphisms in human immunogenes, H. pylori ancestry, and three Helicobacter virulence factors (CagA, VacAs, and VacAm) were utilized for study. Pairwise interactions between matched human polymorphisms and H. pylori ancestry, as well as H. pylori virulence factors and human ancestry, were examined for risk of increased gastric disease severity using multifactor dimensionality reduction (MDR). Though no statistically significant interactions between H. pylori virulence factors and human ancestry were found, this study identified potentially significant interactions between polymorphisms in human immunogenes and H. pylori ancestry. These interactions likely have biological relevance. The findings of this study have numerous potential implications. First, the approach used in this analysis was novel and may serve as a guide to researchers in other fields and for other topics. The research also furthers the knowledge and study of H. pylori infection and gastric outcomes. Importantly, this study analyzed genetic interactions, an often overlooked determinant of disease, in a novel way, with ancestry as a potential explanatory variable. The interactions found in this study will need further validation in larger studies. However, this study and the genetic interactions found have numerous potential benefits, including new knowledge of genetic risk factors of gastric disease severity. This knowledge can be used to develop better models for prediction of gastric disease which would have large implications for epidemiology, genetics, and the risk assessment or treatment of gastric conditions.

There are 8 commonly used algorithms for classifying the ovulatory status of menstrual cycles, however a gold standard algorithm has not been identified. Disagreement between algorithms may influence study results and interpretations. Excessive alcohol consumption and physical activity can have negative effects on menstrual cycle function, including ovulation. Less clear however are the effects of moderate alcohol consumption and moderate amounts of physical activity. The purpose of this dissertation was to evaluate different methods for classifying ovulation status, and to explore modifiable risk factors, including alcohol consumption and physical activity, for anovulation and menstrual cycle dysfunction. We used data from a large prospective cohort study, The BioCycle Study, which followed 259 healthy premenopausal women for 1-2 menstrual cycles. Estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone binding globulin (SHBG) were measured in serum up to 8 times per cycle, timed using fertility monitors to capture relevant cycle phase data. Fiber intake was assessed with multiple 24-h dietary recalls. Alcohol and physical activity were assessed with daily diaries and baseline questionnaires. We calculated the prevalence of anovulation and assessed the effect of fiber consumption on anovulation using each of the 8 algorithms and compared odds ratios (ORs) and 95% confidence intervals (CI). We used linear mixed models to determine the effect of alcohol and physical activity on menstrual cycle hormone values, and generalized linear mixed models to evaluate their effect on anovulation. The prevalence of anovulation ranged from 3.3% to 17.5% across the 8 algorithms. In multivariate analyses of fiber consumption and risk of anovulation, fiber intake was positively associated with anovulation across all algorithms, however precision varied widely; when comparing first to forth quartiles, odds ratios ranged from 3.39 (95% CI: 1.01-11.46) to 7.52 (95% CI: 0.77-73.25). Both physical activity and alcohol were associated with decreased levels of SHBG, but only in the follicular and luteal phases, and had no effect on other hormones or ovulation. The results of this study suggest that moderate levels of physical activity do not have substantial effects on reproductive hormone levels or ovulation status, aside from a slight decrease in SHBG levels.

Includes abstract. Includes bibliographical references.