Physical Sciences and Mathematics Commons^™

The Performance Of Marginal Modeling Methods For Rare Events With Application To Opioid Overdose Mortality And Morbidity, Shawn Nigam

Theses and Dissertations--Epidemiology and Biostatistics

Opioid misuse is a nationwide epidemic, with Kentucky having one of the highest opioid overdose-related fatality rates across all US states. These rates have increased significantly over the past decade, with particularly large increases during the COVID-19 pandemic. This dissertation aims to study the behavior of these increases and the methods for the marginal modeling of count outcomes related to opioid overdose.

Opioid overdose-related fatality rates in Kentucky increased significantly during the COVID-19 pandemic. In this chapter, we characterize the changes in opioid overdose fatality rates in Kentucky and identify associations between potential factors and fatality rates. County-level opioid overdose …

Potential Alzheimer's Disease Plasma Biomarkers, Taylor Estepp

Theses and Dissertations--Epidemiology and Biostatistics

In this series of studies, we examined the potential of a variety of blood-based plasma biomarkers for the identification of Alzheimer's disease (AD) progression and cognitive decline. With the end goal of studying these biomarkers via mixture modeling, we began with a literature review of the methodology. An examination of the biomarkers with demographics and other health factors found evidence of minimal risk of confounding along the causal pathway from biomarkers to cognitive performance. Further study examined the usefulness of linear combinations of biomarkers, achieved via partial least squares (PLS) analysis, as predictors of various cognitive assessment scores and clinical …

A Novel Nonparametric Test For Heterogeneity Detection And Assessment Of Fluid Removal Among Crrt Patients In Icu, Shaowli Kabir

Theses and Dissertations--Epidemiology and Biostatistics

Over the past decade acute kidney injury (AKI) has been occurring among 20%-50% of patients admitted to the intensive care unit (ICU) in United States. Continuous renal replacement therapy (CRRT) has become a popular treatment method among these critically ill patients. But there are multiple complications in implementing this treatment, including discrepancies in practiced and prescribed fluid removal, possibly related to the heterogeneity among these patients. With mixture modeling there have been several techniques in detecting heterogeneity with their specific limitations. In this dissertation a novel nonparametric ‘d test’ will be used to detect heterogeneity among CRRT patients in ICU. …

Opioid Use Disorder Treatment With Buprenorphine: Analysis Of Treatment Utilization And Associated Outcomes In Kentucky, Feitong Lei

Theses and Dissertations--Epidemiology and Biostatistics

Opioid use disorder (OUD) is chronic opioid use that results in clinically significant suffering, impairment, or even death. The opioid epidemic in the United States has become a public health and economic crisis, affecting patients' well-being and the nation's overall health and welfare. Eastern Kentucky was among the first regions affected by the opioid crisis, and Kentucky has historically ranked among the top five states for age-adjusted drug overdose mortality rate.

There are three medications (buprenorphine, methadone, naltrexone) approved by the U.S. Food and Drug Administration to treat OUD. As a partial opioid agonist, buprenorphine is a safe medication for …

Addressing Ascertainment Bias In The Study Of Cardiovascular Disease Burden In Opioid Use Disorders - Application Of Natural Language Processing Of Electronic Health Records, Jade Huang Singleton

Theses and Dissertations--Epidemiology and Biostatistics

In the United States, the prevalence of long-term exposure to opioid drugs, for both medically and nonmedically indicated purposes, has increased considerably since the mid-1990’s. Concerns have emerged about the potential health effects of opioid use. There is also growing interest in other possible connections with opioid use including cardiovascular disease. Electronic health records (EHR) contain information about patient care in the form of structured codes and unstructured notes. Natural language processing (NLP) provides a tool for processing unstructured textual data in EHR clinical notes and extracts useful information for research with structured formats. The purpose of this dissertation was …

Investigations Into The Genetics Of Mixed Pathologies In Dementia, Adam Dugan

Theses and Dissertations--Epidemiology and Biostatistics

Alzheimer’s disease (AD) is an irreversible, progressive brain disorder that leads to a loss of memory and thinking skills. While tremendous progress has been made in our understanding of the genetics underlying AD, currently known genetic variants explain only approximately 30% of the heritable risk of developing AD. One hurdle to AD research is that it can only be definitively diagnosed at autopsy, making cruder, clinic-based diagnoses more common. In recent years, several brain pathologies that mimic AD’s clinical presentation have been identified including brain arteriolosclerosis, hippocampal sclerosis (HS), and, most recently, limbic-predominant age-related TDP-43 encephalopathy (LATE). It has become …

Evaluating The Incidence Of Melanoma And Lung Cancer Of Current And Former Active-Duty U.S. Military Who Were Deployed In Support Of Operation Enduring Freedom And Operation Iraqi Freedom, Brian Kovacic

Theses and Dissertations--Epidemiology and Biostatistics

The incidence of melanoma and lung cancer has been gradually increasing in the United States over the past three decades with the reputed causes due to etiological and environmental exposures, and tobacco usage. There has been concern that melanoma and lung cancer incidence among military personnel may be associated with deployment to environments with intense sun exposure and increased smoking rates due to post-traumatic stress disorder. The aim of this study was to examine associations between deployment in support of Operation Enduring Freedom (OEF) or Operation Iraqi Freedom (OIF), from 2001 through 2015, with subsequent melanoma and lung cancer incidence. …

Design And Analyses Of School-Based Violence Prevention Cluster Randomized Trials, Md. Tofial Azam

Theses and Dissertations--Epidemiology and Biostatistics

Interpersonal violence such as teen dating violence is a severe public health problem. Teen dating violence, including sexual violence (unwanted sexual contacts or activities), physical and psychological dating violence, sexual harassment, and stalking, affects high school students' physical and mental health and academic achievement in the United States. Dating violence is linked to psychological abuse perpetration in the future, depression, anxiety, and hostility. The teen dating violence victimization experience was related to antisocial behavior, drug abuse, increased heavy drinking, depression, suicidal ideation, smoking, and adult interpersonal violence victimization during adolescence. The detrimental effects of interpersonal violence demonstrate the critical importance …

Sexual Behaviors Associated With Online Partner-Seeking Among Men Who Have Sex With Men From Small/Midsized Towns Or Rural Areas In Kentucky, Vira Pravosud

Theses and Dissertations--Epidemiology and Biostatistics

The HIV epidemic remains one of the most significant public health issues in the United States, particularly among men who have sex with men (MSM). New avenues for partner-seeking have emerged over the past three decades, including through the Internet, social media, and geosocial networking applications. Consisting of three cross-sectional studies, this dissertation research aimed to determine associations between the use of various online tools for partner-seeking (hereafter collectively referred to as “apps”) and HIV-related sexual behaviors among 252 young adult MSM residing in small/midsized towns or rural areas in Central Kentucky, a group that has been under-represented in the …

Evaluating The Impacts Of Antidepressant Use On The Risk Of Dementia, Ran Duan

Theses and Dissertations--Epidemiology and Biostatistics

Dementia is a clinical syndrome caused by neurodegeneration or cerebrovascular injury. Patients with dementia suffer from deterioration in memory, thinking, behavior and the ability to perform everyday activities. Since there are no cures or disease-modifying therapies for dementia, there is much interest in identifying modifiable risk factors that may help prevent or slow the progression of cognitive decline. Medications are a common focus of this type of research.

Importantly, according to a report from the Centers for Disease Control and Prevention (CDC), 19.1% of the population aged 60 and over report taking antidepressants during 2011-2014, and this number tends to …

Bivariate Generalization Of The Time-To-Event Conditional Reassessment Method With A Novel Adaptive Randomization Method, Donglin Yan

Theses and Dissertations--Epidemiology and Biostatistics

Phase I clinical trials in oncology aim to evaluate the toxicity risk of new therapies and identify a safe but also effective dose for future studies. Traditional Phase I trials of chemotherapies focus on estimating the maximum tolerated dose (MTD). The rationale for finding the MTD is that better therapeutic effects are expected at higher dose levels as long as the risk of severe toxicity is acceptable. With the advent of a new generation of cancer treatments such as the molecularly targeted agents (MTAs) and immunotherapies, higher dose levels no longer guarantee increased therapeutic effects, and the focus has shifted …

Improved Methods And Selecting Classification Types For Time-Dependent Covariates In The Marginal Analysis Of Longitudinal Data, I-Chen Chen

Theses and Dissertations--Epidemiology and Biostatistics

Generalized estimating equations (GEE) are popularly utilized for the marginal analysis of longitudinal data. In order to obtain consistent regression parameter estimates, these estimating equations must be unbiased. However, when certain types of time-dependent covariates are presented, these equations can be biased unless an independence working correlation structure is employed. Moreover, in this case regression parameter estimation can be very inefficient because not all valid moment conditions are incorporated within the corresponding estimating equations. Therefore, approaches using the generalized method of moments or quadratic inference functions have been proposed for utilizing all valid moment conditions. However, we have found that …

Using Prescription Drug Monitoring Data To Inform Population Level Analysis Of Opioid Analgesic Utilization, Huong T. T. Luu

Theses and Dissertations--Epidemiology and Biostatistics

Increased opioid analgesic (OA) prescribing has been associated with increased risk of prescription opioid diversion, misuse, and abuse. States established prescription drug monitoring programs (PDMPs) to collect and analyze electronic records for dispensed controlled substances to reduce prescription drug abuse and diversion. PDMP data can be used by prescribers for tracking patient’s history of controlled substance prescribing to inform clinical decisions.

The studies in this dissertation are focused on the less utilized potential of the PDMP data to enhance public health surveillance to monitor OA prescribing and co-prescribing and association with opioid overdose mortality and morbidity. Longitudinal analysis of OA …

Improved Standard Error Estimation For Maintaining The Validities Of Inference In Small-Sample Cluster Randomized Trials And Longitudinal Studies, Whitney Ford Tanner

Theses and Dissertations--Epidemiology and Biostatistics

Data arising from Cluster Randomized Trials (CRTs) and longitudinal studies are correlated and generalized estimating equations (GEE) are a popular analysis method for correlated data. Previous research has shown that analyses using GEE could result in liberal inference due to the use of the empirical sandwich covariance matrix estimator, which can yield negatively biased standard error estimates when the number of clusters or subjects is not large. Many techniques have been presented to correct this negative bias; However, use of these corrections can still result in biased standard error estimates and thus test sizes that are not consistently at their …

A Predictive Probability Interim Design For Phase Ii Clinical Trials With Continuous Endpoints, Meng Liu

Theses and Dissertations--Epidemiology and Biostatistics

Phase II clinical trials aim to potentially screen out ineffective and identify effective therapies to move forward to randomized phase III trials. Single-arm studies remain the most utilized design in phase II oncology trials, especially in scenarios where a randomized design is simply not practical. Due to concerns regarding excessive toxicity or ineffective new treatment strategies, interim analyses are typically incorporated in the trial, and the choice of statistical methods mainly depends on the type of primary endpoints. For oncology trials, the most common primary objectives in phase II trials include tumor response rate (binary endpoint) and progression disease-free survival …

Statistical Analyses To Detect And Refine Genetic Associations With Neurodegenerative Diseases, Yuriko Katsumata

Theses and Dissertations--Epidemiology and Biostatistics

Dementia is a clinical state caused by neurodegeneration and characterized by a loss of function in cognitive domains and behavior. Alzheimer’s disease (AD) is the most common form of dementia. Although the amyloid β (Aβ) protein and hyperphosphorylated tau aggregates in the brain are considered to be the key pathological hallmarks of AD, the exact cause of AD is yet to be identified. In addition, clinical diagnoses of AD can be error prone. Many previous studies have compared the clinical diagnosis of AD against the gold standard of autopsy confirmation and shown substantial AD misdiagnosis Hippocampal sclerosis of aging (HS-Aging) …

Mixture Modeling With Applications In Alzheimer's Disease, Frank Appiah

Theses and Dissertations--Epidemiology and Biostatistics

This dissertation involves an application of mixture of regression models to 114 individuals who are cognitively intact (from the Alzheimer's Disease and Neuroimaging Initiative-ADNI, data). The correct number of components in the model were estimated with the Singular BIC (SBIC), marking the first time it has been applied to such a problem. The smallest true model in conjunction with the approximation of SBIC was fixed at 1. The resulting posterior probabilities from the model were used to estimate the probability of a person transitioning and risk plots were obtained that could in principle be used by clinicians to identify patients …

Examining The Activities, Effectiveness, And Contribution Of Local Health Departments Using A National Longitudinal Survey Of Public Health Systems, Lava R. Timsina

Theses and Dissertations--Epidemiology and Biostatistics

Health services research and public health services and systems research in the past have contributed to a strong foundation of evidence-based progress in organizing, financing, and delivering medical care and public health strategies across the United States. The purpose of this dissertation was to examine disparities in public health systems and in the delivery of population health services in communities served by these systems using nationally representative data from the National Longitudinal Survey of Local Public Health Systems (1998, 2006, 2012, and 2014).

Data from the 1998 cohort of 497 local health jurisdictions serving at least 100,000 residents, and from …

Evaluating A Bystander Intervention Program On Reproductive Coercion: Using Quasi-Experimental Design Strategies To Address Methodologic Issues In Randomized Community Prevention Trials, Catherine P. Starnes

Theses and Dissertations--Epidemiology and Biostatistics

Community (or cluster) randomized trials are trials in which communities or groups of individuals (clusters) are randomized to receive the intervention of interest. Community randomized trials frequently more closely resemble a natural experiment than a randomized controlled trial (RCT) following intervention allocation. In particular, the effects of non-compliance can pose methodologic challenges in estimating the intervention effect which may require a quasiexperimental approach in order to minimize bias.

The motivating example to illustrate these issues is the Green Dot High School (GDHS) study. The GDHS study was a longitudinal, cluster-randomized controlled trial designed to assess the effectiveness of a bystander …

Developments In Nonparametric Regression Methods With Application To Raman Spectroscopy Analysis, Jing Guo

Theses and Dissertations--Epidemiology and Biostatistics

Raman spectroscopy has been successfully employed in the classification of breast pathologies involving basis spectra for chemical constituents of breast tissue and resulted in high sensitivity (94%) and specificity (96%) (Haka et al, 2005). Motivated by recent developments in nonparametric regression, in this work, we adapt stacking, boosting, and dynamic ensemble learning into a nonparametric regression framework with application to Raman spectroscopy analysis for breast cancer diagnosis. In Chapter 2, we apply compound estimation (Charnigo and Srinivasan, 2011) in Raman spectra analysis to classify normal, benign, and malignant breast tissue. We explore both the spectra profiles and their derivatives to …

Nonlinear Hierarchical Models For Longitudinal Experimental Infection Studies, Michael David Singleton

Theses and Dissertations--Epidemiology and Biostatistics

Experimental infection (EI) studies, involving the intentional inoculation of animal or human subjects with an infectious agent under controlled conditions, have a long history in infectious disease research. Longitudinal infection response data often arise in EI studies designed to demonstrate vaccine efficacy, explore disease etiology, pathogenesis and transmission, or understand the host immune response to infection. Viral loads, antibody titers, symptom scores and body temperature are a few of the outcome variables commonly studied. Longitudinal EI data are inherently nonlinear, often with single-peaked response trajectories with a common pre- and post-infection baseline. Such data are frequently analyzed with statistical methods …

Data Mining And Pattern Discovery Using Exploratory And Visualization Methods For Large Multidimensional Datasets, Hsin-Fang Li

Theses and Dissertations--Epidemiology and Biostatistics

Oral health problems have been a major public health concern profoundly affecting people’s general health and quality of life. Given that oral health data is composed of several measurable dimensions including clinical measurements, socio-behavioral factors, genetic predispositions, self-reported assessments, and quality of life measures, strategies for analyzing multidimensional data are neither computationally straightforward nor efficient. Researchers face major challenges to identify tools that circumvent the processes of manually probing the data.

The purpose of this dissertation is to provide applications of the proposed methodology on oral health-related data that go beyond identifying risk factors from a single dimension, and to …

Evaluating Retention In Medical Care And Its Impact On The Health Outcomes Of Individuals Living With Human Inmmunodeficiency Virus, Timothy N. Crawford

Theses and Dissertations--Epidemiology and Biostatistics

In the last few years, engagement in medical care among individuals living with HIV has become a major priority among HIV medical providers and public health researchers. Engagement in medical care is an important concept as it involves the process of linking newly diagnosed individuals into medical care and retaining those individuals in care throughout the course of their infection. Although there have been major advances in the management of HIV, like the advent of Highly Active Antiretroviral Therapy, morbidity and mortality due to HIV cannot be fully reduced if the individual does not optimally retain in care. Retention in …