Bayesian Modeling of Latent Heterogeneity in Complex Survey Data and Electronic Health Records

In population health, the study of unobserved, or latent, heterogeneity in longitudinal data may help inform public health interventions. Growth mixture modeling is a flexible tool for modeling latent heterogeneity in longitudinal data. However, the application of growth mixture models to certain data types, namely, complex survey data and electronic health records, is underdeveloped. For valid statistical inferences in complex survey data, features of the sample design must be incorporated into statistical analysis. In electronic health records, the application of growth mixture modeling is challenged by high levels of missing values. In this dissertation, I have three goals: First, I propose a Bayesian growth mixture model for complex survey data in which I directly incorporate features of the complex sample design. Second, I extend a Bayesian growth mixture model of multiple longitudinal health outcomes collected in electronic health records to a shared parameter model that can account for dierent missing data assumptions. Third, I develop open-source software packages in R for each method that can be used for model tting, selection, and checking

Association of Autism With Induced or Augmented Childbirth in North Carolina Birth Record (1990-1998) and Education Research

IMPORTANCE One in 88 children in the United States is diagnosed as having autism spectrum disorder. Significant interest centers on understanding the environmental factors that may contribute to autism risk. OBJECTIVE To examine whether induced (stimulating uterine contractions prior to the onset of spontaneous labor) and/or augmented (increasing the strength, duration, or frequency of uterine contractions with spontaneous onset of labor) births are associated with increased odds of autism. DESIGN, SETTING, AND PARTICIPANTS We performed an epidemiological analysis using multivariable logistic regression modeling involving the North Carolina Detailed Birth Record and Education Research databases. The study featured 625 042 live births linked with school records, including more than 5500 children with a documented exceptionality designation for autism. EXPOSURES Induced or augmented births. MAIN OUTCOMES AND MEASURES Autism as assessed by exceptionality designations in child educational records. RESULTS Compared with children born to mothers who received neither labor induction nor augmentation, children born to mothers who were induced and augmented, induced only, or augmented only experienced increased odds of autism after controlling for potential confounders related to socioeconomic status, maternal health, pregnancy-related events and conditions, and birth year. The observed associations between labor induction/augmentation were particularly pronounced in male children. CONCLUSIONS AND RELEVANCE Our work suggests that induction/augmentation during childbirth is associated with increased odds of autism diagnosis in childhood. While these results are interesting, further investigation is needed to differentiate among potential explanations of the association including underlying pregnancy conditions requiring the eventual need to induce/augment, the events of labor and delivery associated with induction/augmentation, and the specific treatments and dosing used to induce/augment labor (eg, exogenous oxytocin and prostaglandins)

Natural History of Patients with Ischemia and No Obstructive Coronary Artery Disease: The CIAO-ISCHEMIA Study

Background: Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA. Methods: CIAO-ISCHEMIA (Changes in Ischemia and Angina over One year in ISCHEMIA trial screen failures with INOCA) was an international cohort study conducted from 2014-2019 involving angina assessments (Seattle Angina Questionnaire [SAQ]) and stress echocardiograms 1-year apart. This was an ancillary study that included patients with history of angina who were not randomized in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease (CAD) status and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between changes in SAQ Angina Frequency score and change in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and compared CIAO participants with ISCHEMIA participants with obstructive CAD who had stress echocardiography before enrollment, as CIAO participants did. Results: INOCA participants in CIAO were more often female (66% of 208 vs. 26% of 865 ISCHEMIA participants with obstructive CAD, p\u3c0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [IQR 3-5] both groups). Ischemia and angina were not significantly correlated at enrollment in CIAO (p=0.46) or ISCHEMIA stress echocardiography participants (p=0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over one year was not significantly correlated with change in angina (rho=0.029). Conclusions: Improvement in ischemia and improvement in angina were common in INOCA, but not correlated. Our INOCA cohort had a similar degree of inducible wall motion abnormalities to concurrently enrolled ISCHEMIA participants with obstructive CAD. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina

Global Infant Mortality: Correcting for Undercounting

Summary The UN Millennium Development Goals highlight the infant mortality rate (IMR) as a measure of progress in improving neonatal health and more broadly as an indicator of basic health care. However, prior research has shown that IMRs (and in particular perinatal mortality) can be underestimated dramatically, depending on a particular country's live birth criterion, vital registration system, and reporting practices. This study assesses infant mortality undercounting for a global dataset using an approach popularized in productivity economics. Using a one-sided error, frontier estimation technique, we recalculate rates and concurrently derive a measure of likely undercount for each country.infant mortality frontier regression millennium development goals

Implications of construction method and spatial scale on measures of the built environment

Abstract Background Research surrounding the built environment (BE) and health has resulted in inconsistent findings. Experts have identified the need to examine methodological choices, such as development and testing of BE indices at varying spatial scales. We sought to examine the impact of construction method and spatial scale on seven measures of the BE using data collected at two time points. Methods The Children’s Environmental Health Initiative conducted parcel-level assessments of 57 BE variables in Durham, NC (parcel N = 30,319). Based on a priori defined variable groupings, we constructed seven mutually exclusive BE domains (housing damage, property disorder, territoriality, vacancy, public nuisances, crime, and tenancy). Domain-based indices were developed according to four different index construction methods that differentially account for number of parcels and parcel area. Indices were constructed at the census block level and two alternative spatial scales that better depict the larger neighborhood context experienced by local residents: the primary adjacency community and secondary adjacency community. Spearman’s rank correlation was used to assess if indices and relationships among indices were preserved across methods. Results Territoriality, public nuisances, and tenancy were weakly to moderately preserved across methods at the block level while all other indices were well preserved. Except for the relationships between public nuisances and crime or tenancy, and crime and housing damage or territoriality, relationships among indices were poorly preserved across methods. The number of indices affected by construction method increased as spatial scale increased, while the impact of construction method on relationships among indices varied according to spatial scale. Conclusions We found that the impact of construction method on BE measures was index and spatial scale specific. Operationalizing and developing BE measures using alternative methods at varying spatial scales before connecting to health outcomes allows researchers to better understand how methodological decisions may affect associations between health outcomes and BE measures. To ensure that associations between the BE and health outcomes are not artifacts of methodological decisions, researchers would be well-advised to conduct sensitivity analysis using different construction methods. This approach may lead to more robust results regarding the BE and health outcomes

Induction or Augmentation of Labor and Autism-Reply

We recently published a study demonstrating an association between labor induction/augmentation and later diagnosis of autism.1 Letter writers expressed concern about overinterpretation of study findings that may inappropriately influence delivery room practice. In the article, the associated press release, and all media interviews, we relayed a very conservative message emphasizing the distinction between association and causation and clearly stated that the work did not call for any change in obstetric practice. The potential for overinterpretation of scientific research by the press and lay public should not preclude publication of thoughtful scientific investigation. Research is an iterative process. Initial studies highlight directions for future research, the body of evidence grows, and health drivers are clarified

Association of autism with induced or augmented childbirth

Vintzileos and Ananth recently expressed concerns about overinterpretation of findings from our recent study that may inappropriately influence delivery room practice and the potential role of misclassification bias concerning the indicator for autism diagnosis used in our study

Associations of birth outcomes with maternal polybrominated diphenyl ethers and thyroid hormones during pregnancy

Background - Previous research has linked polybrominated diphenyl ether (PBDE) exposure to poor birth outcomes and altered thyroid hormone levels. Objectives - We examined whether maternal PBDE serum levels were associated with infant birth weight (g), head circumference (cm), birth length (cm), and birth weight percentile for gestational age. We explored the potential for a mediating role of thyroid hormone levels. Methods - During 2008–2010, we recruited 140 pregnant women in their third trimester as part of a larger clinical obstetrics study known as Healthy Pregnancy, Healthy Baby. Blood samples were collected during a routine prenatal clinic visit. Serum was analyzed for PBDEs, phenolic metabolites, and thyroid hormones. Birth outcome information was abstracted from medical records. Results - In unadjusted models, a two-fold increase in maternal BDE 153 was associated with an average decrease in head circumference of 0.32 cm (95% CI: − 0.53, − 0.12); however, this association was attenuated after control for maternal risk factors. BDE 47 and 99 were similarly negatively associated but with 95% confidence intervals crossing the null. Associations were unchanged in the presence of thyroid hormones. Conclusions - Our data suggest a potential deleterious association between maternal PBDE levels and infant head circumference; however, confirmatory studies are needed in larger sample sizes. A mediating role of thyroid hormones was not apparent