Biostatistics Commons^™

Generalized Confidence Intervals And Fiducial Intervals For Some Epidemiological Measures., Ionut Bebu, G. Luta, T. Mathew, B. K. Agan

GW Biostatistics Center

For binary outcome data from epidemiological studies, this article investigates the interval estimation of several measures of interest in the absence or presence of categorical covariates. When covariates are present, the logistic regression model as well as the log-binomial model are investigated. The measures considered include the common odds ratio (OR) from several studies, the number needed to treat (NNT), and the prevalence ratio. For each parameter, confidence intervals are constructed using the concepts of generalized pivotal quantities and fiducial quantities. Numerical results show that the confidence intervals so obtained exhibit satisfactory performance in terms of maintaining the coverage probabilities …

Significance Of Epicardial And Intrathoracic Adipose Tissue Volume Among Type 1 Diabetes Patients In The Dcct/Edic: A Pilot Study., Sirous Darabian, Jye-Yu C Backlund, Patricia A Cleary, Nasim Sheidaee, Ionut Bebu, John M. Lachin, Matthew J Budoff, Dcct/Edic Research Group

GW Biostatistics Center

Introduction

Type 1 diabetes (T1DM) patients are at increased risk of coronary artery disease (CAD). This pilot study sought to evaluate the relationship between epicardial adipose tissue (EAT) and intra-thoracic adipose tissue (IAT) volumes and cardio-metabolic risk factors in T1DM.

Method

EAT/IAT volumes in 100 patients, underwent non-contrast cardiac computed tomography in the Diabetes Control and Complications Trial /Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study were measured by a certified reader. Fat was defined as pixels’ density of -30 to -190 Hounsfield Unit. The associations were assessed using–Pearson partial correlation and linear regression models adjusted for gender and age …

Lymphoblastoid Cell Lines As A Tool To Study Inter-Individual Differences In The Response To Glucose., Michael A Grassi, Vidhya R Rao, Siquan Chen, Dingcai Cao, Xiaoyu Gao, Patricia A. Cleary, R Stephanie Huang, Andrew D Paterson, Rama Natarajan, Jalees Rehman, Timothy S Kern

GW Biostatistics Center

BACKGROUND: White blood cells have been shown in animal studies to play a central role in the pathogenesis of diabetic retinopathy. Lymphoblastoid cells are immortalized EBV-transformed primary B-cell leukocytes that have been extensively used as a model for conditions in which white blood cells play a primary role. The purpose of this study was to investigate whether lymphoblastoid cell lines, by retaining many of the key features of primary leukocytes, can be induced with glucose to demonstrate relevant biological responses to those found in diabetic retinopathy.

METHODS: Lymphoblastoid cell lines were obtained from twenty-three human subjects. Differences between high and …

Importance Of Hereditary And Selected Environmental Risk Factors In The Etiology Of Inflammatory Breast Cancer: A Case-Comparison Study., Roxana Moslehi, Elizabeth Freedman, Nur Zeinomar, Carmela Veneroso, Paul H. Levine

Epidemiology Faculty Publications

BACKGROUND: To assess the importance of heredity in the etiology of inflammatory breast cancer (IBC), we compared IBC patients to several carefully chosen comparison groups with respect to the prevalence of first-degree family history of breast cancer.

METHODS: IBC cases (n = 141) were compared to non-inflammatory breast cancer cases (n = 178) ascertained through George Washington University (GWU) with respect to the prevalence of first-degree family history of breast cancer and selected environmental/lifestyle risk factors for breast cancer. Similar comparisons were conducted with subjects from three case-control studies: breast cancer cases (n = 1145) and unaffected controls (n = …

Importance Of Hereditary And Selected Environmental Risk Factors In The Etiology Of Inflammatory Breast Cancer: A Case-Comparison Study., Roxana Moslehi, Elizabeth Freedman, Nur Zeinomar, Carmela Veneroso, Paul H. Levine

Epidemiology Faculty Publications

BACKGROUND: To assess the importance of heredity in the etiology of inflammatory breast cancer (IBC), we compared IBC patients to several carefully chosen comparison groups with respect to the prevalence of first-degree family history of breast cancer.

METHODS: IBC cases (n = 141) were compared to non-inflammatory breast cancer cases (n = 178) ascertained through George Washington University (GWU) with respect to the prevalence of first-degree family history of breast cancer and selected environmental/lifestyle risk factors for breast cancer. Similar comparisons were conducted with subjects from three case-control studies: breast cancer cases (n = 1145) and unaffected controls (n = …

Interruptions Of Antiretroviral Therapy In Children And Adolescents With Hiv Infection In Clinical Practice: A Retrospective Cohort Study In The Usa., Natella Rakhmanina, Kam S Lam, Jaclyn Hern, Heather A. Young, Alex Walters, Amanda D. Castel

Epidemiology Faculty Publications

INTRODUCTION: Changes in combination antiretroviral therapy (cART) throughout childhood challenge the continuity of paediatric HIV treatment. This study aimed to evaluate the prevalence of treatment interruption (TI), including lamivudine (3TC) monotherapy, and the relationship of TI to virologic and immunologic parameters in HIV-infected paediatric patients.

METHODS: Nested within a prospective observational study of a city-wide cohort of HIV-infected persons in the District of Columbia, this sub-study collected retrospective data on antiretroviral therapy, enrolment (endpoint) and historic (lifelong) CD4 counts and HIV RNA viral load (VL) of the paediatric cohort. TI was defined as interruption of cART ≥4 consecutive weeks. Data …

Arsenic In Drinking Water And Lung Cancer Mortality In The United States: An Analysis Based On Us Counties And 30 Years Of Observation (1950-1979)., Hamid Ferdosi, Elisabeth K Dissen, Nana Ama Afari-Dwamena, Ji Li, Rusan Chen, Manning Feinleib, Steven H Lamm

Epidemiology Faculty Publications

Background. To examine whether the US EPA (2010) lung cancer risk estimate derived from the high arsenic exposures (10-934 µg/L) in southwest Taiwan accurately predicts the US experience from low arsenic exposures (3-59 µg/L). Methods. Analyses have been limited to US counties solely dependent on underground sources for their drinking water supply with median arsenic levels of ≥3 µg/L. Results. Cancer risks (slopes) were found to be indistinguishable from zero for males and females. The addition of arsenic level did not significantly increase the explanatory power of the models. Stratified, or categorical, analysis yielded relative risks that hover about 1.00. …

Sample Size Estimation For Genomics Experiments With Dependent End Points, Desmond Koomson

Open Access Theses & Dissertations

In typical genomics studies involving numerous association tests of gene mutations with a disease, error rate control via multiplicity adjustment is paramount because even if all genes were to be non-differentially associated, we would still make some false positives. Many methods exist that incorporate the control of multiplicity for normally distributed endpoints in sample size estimation, but none addresses the issue for non-normally correlated endpoints.

One common practice in the literature is to assume an equal correlation among all differentially associated or expressed genes, thereby using the generalized binomial or beta-binomial model to compute the comparison-wise power of detecting these …

Salvage Brachytherapy For Biochemically Recurrent Prostate Cancer Following Primary Brachytherapy, John M. Lacy, William A. Wilson, Raevti Bole, Li Chen, Ali S. Meigooni, Randall G. Rowland, William H. St. Clair

Urology Faculty Publications

Purpose. In this study, we evaluated our experience with salvage brachytherapy after discovery of biochemical recurrence after a prior brachytherapy procedure. Methods and Materials. From 2001 through 2012 twenty-one patients treated by brachytherapy within University of Kentucky or from outside centers developed biochemical failure and had no evidence of metastases. Computed tomography (CT) scans were evaluated; patients who had an underseeded portion of their prostate were considered for reimplantation. Results. The majority of the patients in this study (61.9%) were low risk and median presalvage PSA was 3.49 (range 17.41–1.68). Mean follow-up was 61 months. At last follow-up after reseeding, …

Causal Inference In Observational Studies With Clustered Data, Meng Wu

Legacy Theses & Dissertations (2009 - 2024)

In this thesis, we study causal inference in observational studies with clustered data.

Estimating Survival Distributions, Important Covariates And Time-Varying Associations, Yan Wu

Legacy Theses & Dissertations (2009 - 2024)

There are three papers each on a different topic in this thesis. The first paper proposes a new objective methodology to estimate any subject specific survival distribution with potential time-varying effect by adjusting approximated polynomial censored survival function with estimated censoring distribution under three different assumptions: uniform censoring, independent censoring and non-informative censoring. The coefficients of the polynomial censored survival function and underlying censoring probability are estimated at each event or censoring time point across the study time frame, which naturally accommodates potential non-proportional hazards along with time-varying effect. An extensive simulation study indicates that the proposed methods usually perform …

Semi-Parametrics Dose Finding Methods, Matthieu Clertant, John O'Quigley

COBRA Preprint Series

We describe a new class of dose finding methods to be used in early phase clinical trials. Under some added parametric conditions the class reduces to the family of continual reassessment method (CRM) designs. Under some relaxation of the underlying structure the method is equivalent to the CCD, mTPI or BOIN classes of designs. These latter designs are non-parametric in nature whereas the CRM class can be viewed as being strongly parametric. The proposed class is characterized as being semi-parametric since it corresponds to CRM with a nuisance parameter. Performance is good, matching that of the CRM class and improving …

Statistical Methods For Environmental Exposure Data Subject To Detection Limits, Yuchen Yang

Theses and Dissertations--Statistics

In this dissertation, we develop unified and efficient nonparametric statistical methods for estimating and comparing environmental exposure distributions in presence of detection limits. In the first part, we propose a kernel-smoothed nonparametric estimator for the exposure distribution without imposing any independence assumption between the exposure level and detection limit. We show that the proposed estimator is consistent and asymptotically normal. Simulation studies demonstrate that the proposed estimator performs well in practical situations. A colon cancer study is provided for illustration. In the second part, we develop a class of test statistics to compare exposure distributions between two groups by using …

Improved Models For Differential Analysis For Genomic Data, Hong Wang

Theses and Dissertations--Statistics

This paper intend to develop novel statistical methods to improve genomic data analysis, especially for differential analysis. We considered two different data type: NanoString nCounter data and somatic mutation data. For NanoString nCounter data, we develop a novel differential expression detection method. The method considers a generalized linear model of the negative binomial family to characterize count data and allows for multi-factor design. Data normalization is incorporated in the model framework through data normalization parameters, which are estimated from control genes embedded in the nCounter system. For somatic mutation data, we develop beta-binomial model-based approaches to identify highly or lowly …

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 …

The Reflected-Shifted-Truncated-Gamma Distribution For Negatively Skewed Survival Data With Application To Pediatric Nephrotic Syndrome, Sophia D. Waymyers

Theses and Dissertations

Negatively skewed survival data arise occasionally in public health fields and in statistical research. Standard distributions such as the exponential, generalized F, generalized gamma, Gompertz, log-logistic, lognormal, Rayleigh, and Weibull distributions are not always well suited to this data. The primary goal of this dissertation is to find a viable alternative for modeling negatively skewed survival data such as the time to first remission for pediatric patients with frequently relapsing or steroid dependent nephrotic syndrome.

We begin with a brief introduction of survival analysis and the nature of pediatric nephrotic syndrome. A meta-analysis on atopy and pediatric nephrotic syndrome using …

Aggregated Quantitative Multifactor Dimensionality Reduction, Rebecca E. Crouch

Theses and Dissertations--Statistics

We consider the problem of making predictions for quantitative phenotypes based on gene-to-gene interactions among selected Single Nucleotide Polymorphisms (SNPs). Previously, Quantitative Multifactor Dimensionality Reduction (QMDR) has been applied to detect gene-to-gene interactions associated with elevated quantitative phenotypes, by creating a dichotomous predictor from one interaction which has been deemed optimal. We propose an Aggregated Quantitative Multifactor Dimensionality Reduction (AQMDR), which exhaustively considers all k-way interactions among a set of SNPs and replaces the dichotomous predictor from QMDR with a continuous aggregated score. We evaluate this new AQMDR method in a series of simulations for two-way and three-way interactions, …

Finding The Cutpoint Of A Continuous Covariate In A Parametric Survival Analysis Model, Kabita Joshi

Theses and Dissertations

In many clinical studies, continuous variables such as age, blood pressure and cholesterol are measured and analyzed. Often clinicians prefer to categorize these continuous variables into different groups, such as low and high risk groups. The goal of this work is to find the cutpoint of a continuous variable where the transition occurs from low to high risk group. Different methods have been published in literature to find such a cutpoint. We extended the methods of Contal and O’Quigley (1999) which was based on the log-rank test and the methods of Klein and Wu (2004) which was based on the …

Sample Size Calculation For Ph Mixture Cure Model, Yihong Zhan

Theses and Dissertations

With the development of advanced medical technology, a significant proportion of patients can be cured of many chronic diseases. Because a substantial fraction of patients have censored information, the standard survival model, such as the proportional hazards (PH) model cannot capture the cured information of patients. Thus PH mixture cure model is developed to handle the survival data with potential cured information. A corresponding sample size formula based on log rank test has been proposed by Wang et al. (2012) and the probability of death in their formula is only contributed by the control arm. However, to calculate the sample …

Parametric Reversed Hazards Model For Left Censored Data With Application To Hiv, Farahnaz Islam

Theses and Dissertations

Left censoring is generally a rare type of censoring in time-to-event data, however there are some fields such as HIV related studies where it commonly occurs. Currently, there is no clear recommendation in the literature on the optimal model and distribution to analyze left-censored data. Recommendations can help researchers apply more accurate models for this type of censoring. This study derives the Parametric Reversed Hazards (PRH) Model for a variety of distributions which may be appropriate for left censored data. The performance of these derived PRH models to analyze HIV viral load data are compared using extensive simulations and a …

Missing Data In Clinical Trial: A Critical Look At The Proportionality Of Mnar And Mar Assumptions For Multiple Imputation, Theophile B. Dipita

College of Graduate Studies: Theses & Dissertations

Randomized control trial is a gold standard of research studies. Randomization helps reduce bias and infer causality. One constraint of these studies is that it depends on participants to obtain the desired data. Whatever the researcher can do, there is a possibility to end up with incomplete data. The problem is more relevant in clinical trials when missing data can be related to the condition under study. The benefits of randomization is compromised by missing data. Multiple imputation is a valid method of treating missing data under the assumption of MAR. Unfortunately this is an unverified assumptions. Current practice advise …

Modeling Spatially Varying Effects Of Chemical Mixtures, Jenna Czarnota

Theses and Dissertations

Cancer incidence is associated with exposures to multiple environmental chemicals, and geographic variation in cancer rates suggests the importance of accommodating spatially varying effects in the analysis of environmental chemical mixtures and disease risk. Traditional regression methods are challenged by the complex correlation patterns inherent among co-occurring chemicals, and the applicability of geographically weighted regression models is limited in the setting of environmental chemical risk analysis. In comparison to traditional methods, weighted quantile sum (WQS) regression performs well in the identification of important environmental exposures, but is limited by the assumption that effects are fixed over space. We present an …

The Association Between Osteoporosis And Early Menopause Following Hysterectomy, Mia Meeyaong-Won Botkin

Walden Dissertations and Doctoral Studies

Osteoporosis is considered to be the most adverse public health disease associated with substantial mortality among postmenopausal women. Hysterectomy, surgically induced menopause, contributes to the early onset of menopause. However, there was no evidence of an association between early menopause following hysterectomy and osteoporosis among postmenopausal women. The purpose of this quantitative study was to examine the association between demographic and behavioral factors and the prevalence of osteoporosis among hysterectomized postmenopausal women. The integrated theory of health behavior change theoretical framework guided study. Cross-sectional secondary data from the 2009-2010 National Health and Nutrition Examination Survey were used. Multiple logistic regression …

Early Sex Work Initiation And Condom Use Among Alcohol-Using Female Sex Workers In Mombasa, Kenya: A Cross-Sectional Analysis, A. M. Parcesepe, Kelly L'Engle, S. L. Martin, S. Green, C. Suchindran, P. Mwarogo

Nursing and Health Professions Faculty Research and Publications

Objectives Early initiation of sex work is prevalent among female sex workers (FSWs) worldwide. The objectives of this study were to investigate if early initiation of sex work was associated with: (1) consistent condom use, (2) condom negotiation self-efficacy or (3) condom use norms among alcohol-using FSWs in Mombasa, Kenya.

Methods In-person interviews were conducted with 816 FSWs in Mombasa, Kenya. Sample participants were: recruited from HIV prevention drop-in centres, 18 years or older and moderate risk drinkers. Early initiation was defined as first engaging in sex work at 17 years or younger. Logistic regression modelled outcomes as a function …

Spatio-Temporal Analysis Of The Occupational Fatal Victimization Of Law Enforcement Officers In The Us, Xueyi Xing

Theses and Dissertations

The models with constant coefficients of the covariates across space and time are commonly used in spatio-temporal analyses. However, the associations between risk factors and the outcome could have locally differential temporal trends in many cases. In this study, a Bayesian latent cluster modeling strategy is employed to identify potential spatial clusters in which locally specific sets of temporally varying coefficients of covariates are allowed. A state-level panel data of police officers occupational fatal victimization for the years 1979-2010 is used. To accommodate overdisperson and excess zeros, a negative binomial model and zero-inflated Poisson/negative binomial models are also utilized. A …

Regression Models For Count Data Based On The Double Poisson Distribution, Rebecca Wardrop

Theses and Dissertations

This paper explores the double Poisson distribution. The probability mass function and the difficulties associated with derivative-based optimization for this distribution are discussed. Stata software developed for estimation of double Poisson regression is detailed. Simulations are used to test the software. Data which are over-, under-, and equidispersed relative to the Poisson are generated and the software is utilized to estimate a regression model, a zero-inflated model, and a marginalized zero-inflated model all based on the double Poisson distribution. The estimated power of the test for φ = 1 for the double Poisson models are compared to the power of …

Score Test Derivations And Implementations For Bivariate Probability Mass And Density Functions With An Application To Copula Functions, Roy Bower

Theses and Dissertations

This dissertation is comprised and grounded in statistical theory with an application to solving real world problems. In particular, the development and implementation of multiple score tests under a variety of scenarios are derived, applied, and interpreted. In chapter 2, I propose a score test for independence of the marginals based on Lakshminarayana’s bivariate Poisson distribution. Each marginal distribution of the bivariate model is a univariate Poisson distribution, and the parameters of the bivariate distribution can be estimated using maximum likelihood methods. The simulation study shows that the score test maintains size close to the nominal level. To assess the …

Semiparametric Estimation Methods For Complex Accelerated Failure Time Model, Yinding Wang

Theses and Dissertations

The proportional hazards (PH) model and the accelerated failure time (AFT) model are the two most popular survival models in fitting the right-censored data. The AFT model is a useful alternative to the PH model, particularly when the PH assumption is not satisfied. Usually, the linear association is assumed with logarithm of survival time in the AFT model. However, the nonlinear association may exist in practice. The first project aims to handle the nonlinear component in the AFT model, which is called the semiparametric additive partial accelerated failure time (AP-AFT) model. Two estimation methods based on the rank-smooth method and …

A Weighted Gene Co-Expression Network Analysis For Streptococcus Sanguinis Microarray Experiments, Erik C. Dvergsten

Theses and Dissertations

Streptococcus sanguinis is a gram-positive, non-motile bacterium native to human mouths. It is the primary cause of endocarditis and is also responsible for tooth decay. Two-component systems (TCSs) are commonly found in bacteria. In response to environmental signals, TCSs may regulate the expression of virulence factor genes.

Gene co-expression networks are exploratory tools used to analyze system-level gene functionality. A gene co-expression network consists of gene expression profiles represented as nodes and gene connections, which occur if two genes are significantly co-expressed. An adjacency function transforms the similarity matrix containing co-expression similarities into the adjacency matrix containing connection strengths. Gene …

Selecting Spatial Scale Of Area-Level Covariates In Regression Models, Lauren Grant

Theses and Dissertations

Studies have found that the level of association between an area-level covariate and an outcome can vary depending on the spatial scale (SS) of a particular covariate. However, covariates used in regression models are customarily modeled at the same spatial unit. In this dissertation, we developed four SS model selection algorithms that select the best spatial scale for each area-level covariate. The SS forward stepwise, SS incremental forward stagewise, SS least angle regression (LARS), and SS lasso algorithms allow for the selection of different area-level covariates at different spatial scales, while constraining each covariate to enter at most one spatial …