Biostatistics Commons^™

Vitamin D Status And Demographic And Lifestyle Determinants Among Adults In The United States (Nhanes 2001-2006), Yan Cao, Katie L. Callahan, Sreenivas P. Veeranki, Yang Chen, Ying Liu, Shimin Zheng

ETSU Faculty Works

This study looked at risk factors associated with vitamin D levels in the body among a representative sample of adults in the U.S., NHANES III (2001-2006) data were used to assess the relationship between several demographic and health risk factors and vitamin D levels in the body. The Baseline-Category Logit Model was used to test the association between vitamin D level and the potential risk factors age, education, ethnicity, poverty status, physical activity, smoking, alcohol, obesity, diabetes and total cholesterol with both genders. Vitamin D insufficiency and deficiency were significantly associated with age, race, education, physical activity, obesity, diabetes and …

Methods For Exploring Treatment Effect Heterogeneity In Subgroup Analysis: An Application To Global Clinical Trials, I. Manjula Schou, Ian C. Marschner

COBRA Preprint Series

Multi-country randomised clinical trials (MRCTs) are common in the medical literature and their interpretation has been the subject of extensive recent discussion. In many MRCTs, an evaluation of treatment effect homogeneity across countries or regions is conducted. Subgroup analysis principles require a significant test of interaction in order to claim heterogeneity of treatment effect across subgroups, such as countries in a MRCT. As clinical trials are typically underpowered for tests of interaction, overly optimistic expectations of treatment effect homogeneity can lead researchers, regulators and other stakeholders to over-interpret apparent differences between subgroups even when heterogeneity tests are insignificant. In this …

Pgs: A Tool For Association Study Of High-Dimensional Microrna Expression Data With Repeated Measures, Yinan Zheng, Zhe Fei, Wei Zhang, Justin Starren, Lei Liu, Andrea Baccarelli, Yi Li, Lifang Hou

The University of Michigan Department of Biostatistics Working Paper Series

Motivation: MicroRNAs (miRNAs) are short single-stranded non-coding molecules that usually function as negative regulators to silence or suppress gene expression. Due to interested in the dynamic nature of the miRNA and reduced microarray and sequencing costs, a growing number of researchers are now measuring high-dimensional miRNAs expression data using repeated or multiple measures in which each individual has more than one sample collected and measured over time. However, the commonly used site-by-site multiple testing may impair the value of repeated or multiple measures data by ignoring the inherent dependent structure, which lead to problems including underpowered results after multiple comparison …

Targeted Maximum Likelihood Estimation Using Exponential Families, Iván Díaz, Michael Rosenblum

Johns Hopkins University, Dept. of Biostatistics Working Papers

Targeted maximum likelihood estimation (TMLE) is a general method for estimating parameters in semiparametric and nonparametric models. Each iteration of TMLE involves fitting a parametric submodel that targets the parameter of interest. We investigate the use of exponential families to define the parametric submodel. This implementation of TMLE gives a general approach for estimating any smooth parameter in the nonparametric model. A computational advantage of this approach is that each iteration of TMLE involves estimation of a parameter in an exponential family, which is a convex optimization problem for which software implementing reliable and computationally efficient methods exists. We illustrate …

Gwas Identifies An Nat2 Acetylator Status Tag Single Nucleotide Polymorphism To Be A Major Locus For Skin Fluorescence, Karen M. Eny, Helen L. Lutgers, John Maynard, Barbara E.K. Klein, Kristine E. Lee, Patricia A. Cleary, +20 Additional Authors

Epidemiology Faculty Publications

Aims/hypothesis

Skin fluorescence (SF) is a non-invasive marker of AGEs and is associated with the long-term complications of diabetes. SF increases with age and is also greater among individuals with diabetes. A familial correlation of SF suggests that genetics may play a role. We therefore performed parallel genome-wide association studies of SF in two cohorts.

Methods

Cohort 1 included 1,082 participants, 35–67 years of age with type 1 diabetes. Cohort 2 included 8,721 participants without diabetes, aged 18–90 years.

Results

rs1495741 was significantly associated with SF in Cohort 1 (p < 6 × 10−10), which is known to tag theNAT2 acetylator phenotype. The fast acetylator genotype was associated …

Abcc9 Gene Polymorphism Is Associated With Hippocampal Sclerosis Of Aging Pathology, Peter T. Nelson, Steven Estus, Erin L. Abner, Ishita Parikh, Manasi Malik, Janna H. Neltner, Eseosa Ighodaro, Wang-Xia Wang, Bernard R. Wilfred, Li-San Wang, Walter A. Kukull, Kannabiran Nandakumar, Mark L. Farman, Wayne W. Poon, Maria M. Corrada, Claudia H. Kawas, David H. Cribbs, David A. Bennett, Julie A. Schneider, Eric B. Larson, Paul K. Crane, Otto Valladares, Frederick A. Schmitt, Richard J. Kryscio, Gregory A. Jicha, Charles D. Smith, Stephen W. Scheff, Joshua A. Sonnen, Jonathan L. Haines, Margaret A. Pericak-Vance, Richard Mayeux, Lindsay A. Farrer, Linda J. Van Eldik, Craig Horbinski, Robert C. Green, Marla Gearing, Leonard W. Poon, Patricia L. Kramer, Randall L. Woltjer, Thomas J. Montine, Amanda B. Partch, Alexander J. Rajic, Katierose Richmire, Sarah E. Monsell, Gerard D. Schellenberg, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

Hippocampal sclerosis of aging (HS-Aging) is a high-morbidity brain disease in the elderly but risk factors are largely unknown. We report the first genome-wide association study (GWAS) with HS-Aging pathology as an endophenotype. In collaboration with the Alzheimer's Disease Genetics Consortium, data were analyzed from large autopsy cohorts: (#1) National Alzheimer's Coordinating Center (NACC); (#2) Rush University Religious Orders Study and Memory and Aging Project; (#3) Group Health Research Institute Adult Changes in Thought study; (#4) University of California at Irvine 90+ Study; and (#5) University of Kentucky Alzheimer's Disease Center. Altogether, 363 HS-Aging cases and 2,303 controls, all pathologically …

Partially-Latent Class Models (Plcm) For Case-Control Studies Of Childhood Pneumonia Etiology, Zhenke Wu, Maria Deloria-Knoll, Laura L. Hammitt, Scott L. Zeger

Johns Hopkins University, Dept. of Biostatistics Working Papers

In population studies on the etiology of disease, one goal is the estimation of the fraction of cases attributable to each of several causes. For example, pneumonia is a clinical diagnosis of lung infection that may be caused by viral, bacterial, fungal, or other pathogens. The study of pneumonia etiology is challenging because directly sampling from the lung to identify the etiologic pathogen is not standard clinical practice in most settings. Instead, measurements from multiple peripheral specimens are made. This paper considers the problem of estimating the population etiology distribution and the individual etiology probabilities. We formulate the scientific …

Deductive Derivation And Computerization Of Compatible Semiparametric Efficient Estimation, Constantine E. Frangakis, Tianchen Qian, Zhenke Wu, Ivan Diaz

U.C. Berkeley Division of Biostatistics Working Paper Series

Researchers often seek robust inference for a parameter through semiparametric estimation. Efficient semiparametric estimation currently requires theoretical derivation of the efficient influence function (EIF), which can be a challenging and time-consuming task. If this task can be computerized, it can save dramatic human effort, which can be transferred, for example, to the design of new studies. Although the EIF is, in principle, a derivative, simple numerical differentiation to calculate the EIF by a computer masks the EIF's functional dependence on the parameter of interest. For this reason, the standard approach to obtaining the EIF has been the theoretical construction of …

Dose Expansion Cohorts In Phase I Trials, Alexia Iasonos, John O'Quigley

Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series

A rapidly increasing number of Phase I dose-finding studies, and in particular those based on the standard 3+3 design, frequently prolong the study and include dose expansion cohorts (DEC) with the goal to better characterize the toxicity profiles of experimental agents and to study disease specific cohorts. These trials consist of two phases: the usual dose escalation phase that aims to establish the maximum tolerated dose (MTD) and the dose expansion phase that accrues additional patients, often with different eligibility criteria, and where additional information is being collected. Current protocols typically do not specify whether the MTD will be updated …

Variable Selection For Zero-Inflated And Overdispersed Data With Application To Health Care Demand In Germany, Zhu Wang, Shuangge Ma, Ching-Yun Wang

COBRA Preprint Series

In health services and outcome research, count outcomes are frequently encountered and often have a large proportion of zeros. The zero-inflated negative binomial (ZINB) regression model has important applications for this type of data. With many possible candidate risk factors, this paper proposes new variable selection methods for the ZINB model. We consider maximum likelihood function plus a penalty including the least absolute shrinkage and selection operator (LASSO), smoothly clipped absolute deviation (SCAD) and minimax concave penalty (MCP). An EM (expectation-maximization) algorithm is proposed for estimating the model parameters and conducting variable selection simultaneously. This algorithm consists of estimating penalized …

Targeted Covariate-Adjusted Response-Adaptive Lasso-Based Randomized Controlled Trials, Antoine Chambaz, Wenjing Zheng, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

We present a new covariate-adjusted response-adaptive randomized controlled trial design and inferential procedure built on top of it. The procedure is targeted in the sense that (i) the sequence of randomization schemes is group-sequentially determined by targeting a user-specified optimal randomization design based on accruing data and, (ii) our estimator of the user-specified parameter of interest, seen as the value of a functional evaluated at the true, unknown distribution of the data, is targeted toward it by following the paradigm of targeted minimum loss estimation. We focus for clarity on the case that the parameter of interest is the marginal …

Variable-Domain Functional Regression For Modeling Icu Data, Jonathan E. Gellar, Elizabeth Colantuoni, Dale M. Needham, Ciprian M. Crainiceanu

Johns Hopkins University, Dept. of Biostatistics Working Papers

We introduce a class of scalar-on-function regression models with subject-specific functional predictor domains. The fundamental idea is to consider a bivariate functional parameter that depends both on the functional argument and on the width of the functional predictor domain. Both parametric and nonparametric models are introduced to fit the functional coefficient. The nonparametric model is theoretically and practically invariant to functional support transformation, or support registration. Methods were motivated by and applied to a study of association between daily measures of the Intensive Care Unit (ICU) Sequential Organ Failure Assessment (SOFA) score and two outcomes: in-hospital mortality, and physical impairment …

Sieve Plateau Variance Estimators: A New Approach To Confidence Interval Estimation For Dependent Data, Molly M. Davies, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Suppose we have a data set of n-observations where the extent of dependence between them is poorly understood. We assume we have an estimator that is squareroot-consistent for a particular estimand, and the dependence structure is weak enough so that the standardized estimator is asymptotically normally distributed. Our goal is to estimate the asymptotic variance of the standardized estimator so that we can construct a Wald-type confidence interval for the estimate. In this paper we present an approach that allows us to learn this asymptotic variance from a sequence of influence function based candidate variance estimators. We focus on time …

Patient Rule Induction Method For Subgroup Identification Given Censored Data., Patrick James Trainor

Electronic Theses and Dissertations

The identification of subgroups in clinical studies is an important aspect of personalized medicine. In order to develop tailored therapeutics, the factors that characterize subgroups with differential prognosis, response to treatment, and incidence of adverse events or toxicities must be elucidated. We present a generalization of a statistical learning algorithm, Patient Rule Induction Method (PRIM), that is well suited for this task given a right-censored time-to-event outcome measure. This algorithm works to recursively partition a covariate space into mutually exclusive boxes that can be utilized to define subgroups. Conceptually the algorithm is similar to classification and regression trees but rather …

Statistical Methods For Assessing Treatment Effects For Observational Studies., Kristopher C. Gardner 1984-

Electronic Theses and Dissertations

Though randomized clinical (RCTs) trials are the gold standard for comparing treatments, they are often infeasible or exclude clinically important subjects, or generally represent an idealized medical setting rather than real practice. Observational data provide an opportunity to study practice-based evidence, but also present challenges for analysis. Traditional statistical methods which are suitable for RCTs may be inadequate for the observational studies. In this project, four of the most popular statistical methods for observational studies: ANCOVA, propensity score matching, regression with the propensity score as a covariate, and instrumental variables (IV) are investigated through application to MarketScan insurance claims data. …

The Association Between The Il-1 Pathway, Isaac C. Wun

Dissertations and Theses (Open Access)

Cutaneous malignant melanoma (CMM) is a potentially lethal malignancy that warrants attention and further research, as it is known to that there is an increasing rate of incidence in theUnited States, and it is also known that exposure to UV light is its most crucial risk factor, and family history of melanoma is also an important risk factor. Melanoma is an aggressive and lethal cancer in humans. There are an estimated new 132,000 melanoma cases annually worldwide, and the trend has doubled in the past 20 years. However, attempts to treat melanoma have encountered considerable resistance and remained ineffective. The …

Assessing The Impact Of Misclassification When Comparing Prevalence Data: A Novel Sensitivity Analysis Approach, Ninet Sinaii, Sean D. Cleary, Pamela Stratton

Epidemiology Faculty Publications

Background: A simple sensitivity analysis technique was developed to assess the impact of misclassification and verify observed prevalence differences between distinct populations.

Methods: The prevalence of self-reported comorbid diseases in 4,331 women with surgically-diagnosed endometriosis was compared to published clinical and population-based prevalence estimates. Disease prevalence misclassification was assessed by assuming over-reporting in the study sample and under-reporting in the general (comparison) population. Over- and under-reporting by 10%, 25%, 50%, 75%, and 90% was used to create a 5×5 table for each disease. The new prevalences represented by each table cell were compared by p-values, prevalence odds ratios, and 95% …

Application And Extension Of Weighted Quantile Sum Regression For The Development Of A Clinical Risk Prediction Tool, Ghalib Bello

Theses and Dissertations

In clinical settings, the diagnosis of medical conditions is often aided by measurement of various serum biomarkers through the use of laboratory tests. These biomarkers provide information about different aspects of a patient’s health and the overall function of different organs. In this dissertation, we develop and validate a weighted composite index that aggregates the information from a variety of health biomarkers covering multiple organ systems. The index can be used for predicting all-cause mortality and could also be used as a holistic measure of overall physiological health status. We refer to it as the Health Status Metric (HSM). Validation …

A Study Of The Relationship Between Childhood Body Size And Adult Blood Pressure, Cardiovascular Structure And Function, Yangyang Deng

Theses and Dissertations

BACKGROUND: Little is known of the effects of obesity, body size and body composition, and blood pressure (BP) in childhood on hypertension (HBP) and cardiac structure and function in adulthood due to the lack of long-term serial data on these parameters from childhood into adulthood. In the present study, we are poised to analyze these serial data from the Fels Longitudinal Study (FLS) to evaluate the extent to which body size during childhood determines HBP and cardiac structure and function in the same individuals in adulthood through mathematical modeling. METHODS: The data were from 412 males and 403 females in …

Socioeconomic And Demographic Factors Modify The Association Between Informal Caregiving And Health In The Sandwich Generation, Elizabeth K. Do, Steven A. Cohen, Monique J. Brown Ph.D., Mph

Faculty Publications

Background

Nearly 50 million Americans provide informal care to an older relative or friend. Many are members of the “sandwich generation”, providing care for elderly parents and children simultaneously. Although evidence suggests that the negative health consequences of caregiving are more severe for sandwiched caregivers, little is known about how these associations vary by sociodemographic factors.

Methods

We abstracted data from the Behavioral Risk Factor Surveillance System to determine how the association between caregiving and health varies by sociodemographic factors, using ordinal logistic regression with interaction terms and stratification by number of children, income, and race/ethnicity.

Results

The association between …