Public Health Commons^™

Mediation Analysis Of Gestational Age, Congenital Heart Defects, And Infant Birth-Weight, Adane F. Wogu, Christopher A. Loffredo, Ionut Bebu, George Luta

GW Biostatistics Center

Background

In this study we assessed the mediation role of the gestational age on the effect of the infant’s congenital heart defects (CHD) on birth-weight.

Methods

We used secondary data from the Baltimore-Washington Infant Study (1981–1989). Mediation analysis was employed to investigate whether gestational age acted as a mediator of the association between CHD and reduced birth-weight. We estimated the mediated effect, the mediation proportion, and their corresponding 95% confidence intervals (CI) using several methods.

Results

There were 3362 CHD cases and 3564 controls in the dataset with mean birth-weight of 3071 (SD = 729) and 3353 (SD = 603) …

A More Efficient Nonparametric Test Of Symmetry Based On Overlapping Coefficient, Hani M. Samawi, Robert L. Vogel

Biostatistics Faculty Publications

In this paper we provide a more efficient nonparametric test of symmetry based on the empirical overlap coefficient using kernel density estimation applied to an extreme order statistics, namely extreme ranked set sampling. Our simulation investigation reveals that our proposed test of symmetry is at least as powerful as currently available tests of symmetry. Intensive simulation is conducted to examine the power of the proposed test. An illustration is provided using cardiac output and body weight of neonates in a neonatal intensive care unit.

Simulation Based Evaluation Of Multiscale Small Area Health Models, Purbasha Dasgupta

Theses and Dissertations

The effects of scale on the analysis of spatial data, often referred to as the modifiable areal unit problem in spatial studies, is one of the issues often encountered in small area health models. These spatial effects of scale are also seen in the areas of disease mapping where data are usually available in counts. Often there is a need to consider the different scales of aggregation that exist within count data, since inferences based on analyses can vary if we change the definition of the unit of analysis. This thesis provides a framework that describes the distribution of relative …

Access To Hiv Prevention And Care For Hiv-Exposed And Hiv-Infected Children: A Qualitative Study In Rural And Urban Mozambique, Caroline De Schacht, Carlota Lucas, Caterina Mboa, Michelle Gill, Eugenia Macasse, Stelio A. Dimande, Emily A. Bobrow, Laura Guay

Epidemiology Faculty Publications

Background Follow-up of HIV-exposed children for the delivery of prevention of mother-to-child transmission services and for early diagnosis and treatment of HIV infection is critical to their survival. Despite efforts, uptake of postnatal care for these children remains low in many subSaharan African countries. Methods A qualitative study was conducted in three provinces in Mozambique to identify motivators and barriers to improve uptake of and retention in HIV prevention, care and treatment services for HIV-exposed and HIV-infected children. Participant recommendations were also gathered. Individual interviews (n=79) and focus group discussions (n=32) were conducted with parents/caregivers, grandmothers, community leaders and health …

Prognostic Value Of Lymphocyte Vascular Density And E-Cadherin In Inflammatory Breast Cancer, Paul H. Levine, Heather J. Hoffman, Audra Macneil, Salman Hashmi, Sherry X. Yang, Stephen Hewitt, Kenneth L. Van Golen, Sandra M. Swain

Epidemiology Faculty Publications

Background: We recently evaluated four laboratory assays, vascular endothelial growth factor D (VEGF-D), E-cadherin, lymphatic vessel density (LVD) measured by podoplanin, and intra-lymphatic tumor emboli (ILTE), which showed notable differences between inflammatory breast cancer (IBC) and non-inflammatory locally advanced breast cancer (LABC). In this study we investigated the potential of the three most quantitatively measured markers, E-cadherin, LVD and VEGF-D, to predict survival in the IBC patients.

Materials and Methods: This study involved the 100 cases identified in the Inflammatory Breast Cancer Registry (IBCR) whose tumors were previously evaluated for the four assays noted above. Living patients were recontacted and …

Identifying Change Points In A Covariate Effect On Time-To-Event Analysis With Reduced Isotonic Regression, Yong Ma, Yinglei Lai, John M. Lachin

GW Biostatistics Center

Isotonic regression is a useful tool to investigate the relationship between a quantitative covariate and a time-to-event outcome. The resulting non-parametric model is a monotonic step function of a covariate X and the steps can be viewed as change points in the underlying hazard function. However, when there are too many steps, over-fitting can occur and further reduction is desirable. We propose a reduced isotonic regression approach to allow combination of small neighboring steps that are not statistically significantly different. In this approach, a second stage, the reduction stage, is integrated into the usual monotonic step building algorithm by comparing …

The Effectiveness Of Teleglaucoma Versus In-Patient Examination For Glaucoma Screening: A Systematic Review And Meta-Analysis, Sera-Melisa Thomas, Maya M Jeyaraman, Maya Jeyaraman, William G Hodge, Cindy Hutnik, John Costella, Monali S Malvankar-Mehta

Epidemiology and Biostatistics Publications

BACKGROUND: Glaucoma is the leading cause of irreversible visual impairment in the world affecting 60.5 million people worldwide in 2010, which is expected to increase to approximately 79.6 million by 2020. Therefore, glaucoma screening is important to detect, diagnose, and treat patients at the earlier stages to prevent disease progression and vision loss. Teleglaucoma uses stereoscopic digital imaging to take ocular images, which are transmitted electronically to an ocular specialist. The purpose is to synthesize literature to evaluate teleglaucoma, its diagnostic accuracy, healthcare system benefits, and cost-effectiveness.

METHODS: A systematic search was conducted to help locate published and unpublished studies. …

Assessing The Social And Ecological Factors That Influence Childhood Overweight And Obesity, Katie Callahan

Electronic Theses and Dissertations

The prevalence of childhood overweight and obesity is increasing at an alarming rate in the United States. Currently more than 1 in 3 children aged 2-19 are overweight or obese. This is of major concern because childhood overweight and obesity leads to chronic conditions such as type II diabetes and tracks into adulthood, where more severe adverse health outcomes arise. In this study I used the premise of the social ecological model (SEM) to analyze the common levels that a child is exposed to daily; the intrapersonal level, the interpersonal level, the school level, and the community level to better …

Overview Of Inference About Roc Curve In Medical Diagnosis, Jingjing Yin

Biostatistics Faculty Publications

Medical diagnosis aims to identify diseased individuals through the evaluation of the measurements of some biomarkers by performing a diagnostic test based on some biomarker measurements. Biomarkers are measured on either discrete or continuous scale and continuous biomarkers are utilized more often in medical practice. This article introduces the most popular tool for evaluating continuous biomarkers: the Receiver Operating Characteristic (ROC) curve.

A Review Of Software For Analyzing Molecular Sequences, Haema Nilakanta, Kimberly L. Drews, Suzanne Firrell, Mary A. Foulkes, Kathleen A. Jablonski

GW Biostatistics Center

Background Over the past ten years, there has been an explosion of microbiome research. Many software packages for analyzing microbial sequences such as the 16S gene from 454 sequencers and Illumina platforms are available. But for a new researcher, it is difficult to know which package to choose. We present a systematic review of packages for the analysis of molecular sequences used to describe and compare microbial communities. This review gives students and researchers information to help choose the best analytic pipeline for their project. To the best of our knowledge, this is the first review of such software.

Findings …

Trends In The Prevalence And Mortality Of Cognitive Impairment In The United States: Is There Evidence Of A Compression Of Cognitive Morbidity, Kenneth Langa, Eric Larson, Jason Karlawish, David Cutler, Mohammed Kabeto, Scott Kim, Allison Rosen

Jason Karlawish

BACKGROUND: Recent medical, demographic, and social trends might have had an important impact on the cognitive health of older adults. To assess the impact of these multiple trends, we compared the prevalence and 2-year mortality of cognitive impairment (CI) consistent with dementia in the United States in 1993 to 1995 and 2002 to 2004. METHODS: We used data from the Health and Retirement Study (HRS), a nationally representative population-based longitudinal survey of U.S. adults. Individuals aged 70 years or older from the 1993 (N = 7,406) and 2002 (N = 7,104) waves of the HRS were included. CI was determined …

Enhanced Precision In The Analysis Of Randomized Trials With Ordinal Outcomes, Iván Díaz, Elizabeth Colantuoni, Michael Rosenblum

Johns Hopkins University, Dept. of Biostatistics Working Papers

We present a general method for estimating the effect of a treatment on an ordinal outcome in randomized trials. The method is robust in that it does not rely on the proportional odds assumption. Our estimator leverages information in prognostic baseline variables, and has all of the following properties: (i) it is consistent; (ii) it is locally efficient; (iii) it is guaranteed to match or improve the precision of the standard, unadjusted estimator. To the best of our knowledge, this is the first estimator of the causal relation between a treatment and an ordinal outcome to satisfy these properties. We …

Applications Of The Wei-Lachin Multivariate One-Sided Test For Multiple Outcomes On Possibly Different Scales, John M. Lachin

GW Biostatistics Center

Many studies aim to assess whether a therapy has a beneficial effect on multiple outcomes simultaneously relative to a control. Often the joint null hypothesis of no difference for the set of outcomes is tested using separate tests with a correction for multiple tests, or using a multivariate T2-like MANOVA or global test. However, a more powerful test in this case is a multivariate one-sided or one-directional test directed at detecting a simultaneous beneficial treatment effect on each outcome, though not necessarily of the same magnitude. The Wei-Lachin test is a simple 1 df test obtained from a simple …

Hiv Testing Implementation In Two Urban Cities: Practice, Policy And Perceived Barriers, Camden J. Hallmark, Jennifer Skillicorn, Thomas P. Giordano, Jessica A. Davila, Marlene Mcneese, Nestor Rocha, Avemaria Smith, Stacey Cooper, Amanda D. Castel

Epidemiology Faculty Publications

Background

Although funding has supported the scale up of routine, opt-out HIV testing in the US, variance in implementation mechanisms and barriers in high-burden jurisdictions remains unknown.

Methods

We conducted a survey of health care organizations in Washington, DC and Houston/Harris County to determine number of HIV tests completed in 2011, policy and practices associated with HIV testing, funding mechanisms, and reported barriers to testing in each jurisdiction and to compare results between jurisdictions.

Results

In 2012, 43 Houston and 35 DC HIV-testing organizations participated in the survey. Participants represented 85% of Department of Health-supported testers in DC and 90% …

Stratified Meta-Analysis To Examine Data Biases In Lung Cancer Studies Of Refinery Workers, Sherman Selix

Yale Day of Data

Petroleum refineries employ a variety of workers who historically experienced different potentials for asbestos exposure depending on job tasks. Associations between petroleum refinery work and lung cancer related to occupational asbestos exposure have been quantified among various locations, corporations, and time periods. To combine the data from several individual refinery studies and examine an overall effect, a systematic review and stratified meta-analysis was employed. Using set search terms among four databases, 112 potential publications were identified, of which 29 qualified for meta-analysis. Risk estimates and confidence intervals were extracted from these publications to construct four separate datasets. Inverse variance weighting …

Lung Flute Improves Symptoms And Health Status In Copd With Chronic Bronchitis: A 26 Week Randomized Controlled Trial, Sanjay Sethi, Jingjing Yin, Pamela K. Anderson

Biostatistics Faculty Publications

Background: Chronic obstructive pulmonary disease (COPD) is characterized by mucus hypersecretion that contributes to disease related morbidity and is associated with increased mortality. The Lung Flute® is a new respiratory device that produces a low frequency acoustic wave with moderately vigorous exhalation to increase mucus clearance. We hypothesized that the Lung Flute, used on a twice daily basis will provide clinical benefit to patients with COPD with chronic bronchitis.

Methods: We performed a 26 week randomized, non-intervention controlled, single center, open label trial in 69 patients with COPD and Chronic Bronchitis. The primary endpoint was change in respiratory symptoms measured …

Cluster Randomized Trials And Statistical Power, Stephen A. Lauer, Nicholas G. Reich

Nicholas G Reich

The cluster-randomized trial (CRT) is a common study design in public health research. In situations where dividing a group of individuals into treatment and controls is unethical or impossible, a CRT design maintains the strengths of a randomized study design. By comparing the outcomes of small populations (clusters), we can observe the impacts of interventions on the community as a whole. Public health researchers around the world have utilized CRTs to measure the effect of, for example, de-worming medication on school attendance, financial incentives on doctor absenteeism, and providing chlorine to waterholes. The CRT can be a potent tool, however …

Evaluating Predictors Of An Individual’S Dietary Intake Latent Value Under Different Mixed Models, Shuli Yu

Doctoral Dissertations

The accurate estimation of an individual’s usual dietary intake is important since the estimates are essential to uncover the diet-disease relationships. This study explores a more accurate method to estimate an individual’s latent value of usual dietary intake when it is repeatedly measured using a 24-hour dietary recall (24HR) and seven day dietary recall (7DDR), accounting for random measurement error and bias. The performance of the (empirical) predictor of subject’s latent value obtained under the finite population mixed model (FPMM) framework is compared with those obtained under the usual mixed model and the measurement error model through a simulation study. …

Depicting Estimates Using The Intercept In Meta-Regression Models: The Moving Constant Technique, Blair T. Johnson Dr., Tania B. Huedo-Medina Dr.

Blair T. Johnson

In any scientific discipline, the ability to portray research patterns graphically often aids greatly in interpreting a phenomenon. In part to depict phenomena, the statistics and capabilities of meta-analytic models have grown increasingly sophisticated. Accordingly, this article details how to move the constant in weighted meta-analysis regression models (viz. “meta-regression”) to illuminate the patterns in such models across a range of complexities. Although it is commonly ignored in practice, the constant (or intercept) in such models can be indispensible when it is not relegated to its usual static role. The moving constant technique makes possible estimates and confidence intervals at …

Incidence And Trends Of Blastomycosis-Associated Hospitalizations In The United States, Amy E. Seitz, Naji Younes, Claudia A. Steiner, Rebecca Prevots

Epidemiology Faculty Publications

We used the State Inpatient Databases from the United States Agency for Healthcare Research and Quality to provide state-specific age-adjusted blastomycosis-associated hospitalization incidence throughout the entire United States. Among the 46 states studied, states within the Mississippi and Ohio River valleys had the highest age-adjusted hospitalization incidence. Specifically, Wisconsin had the highest age-adjusted hospitalization incidence (2.9 hospitalizations per 100,000 person-years). Trends were studied in the five highest hospitalization incidence states. From 2000 to 2011, blastomycosis-associated hospitalizations increased significantly in Illinois and Kentucky with an average annual increase of 4.4% and 8.4%, respectively. Trends varied significantly by state. Overall, 64% of …

Lifestyle And Metformin Interventions Have A Durable Effect To Lower Crp And Tpa Levels In The Diabetes Prevention Program Except In Those Who Develop Diabetes., Ronald B Goldberg, Marinella G Temprosa, Kieren J Mather, Trevor J Orchard, Abbas E Kitabchi, Karol E Watson

GW Biostatistics Center

OBJECTIVE: We evaluate whether lifestyle and metformin interventions used to prevent diabetes have durable effects on markers of inflammation and coagulation and whether the effects are influenced by the development of diabetes.

RESEARCH DESIGN AND METHODS: The Diabetes Prevention Program was a controlled clinical trial of 3,234 subjects at high risk for diabetes who were randomized to lifestyle, metformin, or placebo interventions for 3.4 years. Diabetes was diagnosed semiannually by fasting glucose and annually by oral glucose tolerance testing. In addition to baseline testing, anthropometry was performed every 6 months; fasting insulin yearly; and hs-CRP, tissue plasminogen activator (tPA), and …

Inflammatory Breast Cancer Clusters: A Hypothesis, Paul H. Levine, Salman Hashmi, Ashley A. Minaei, Carmela Veneroso

Epidemiology Faculty Publications

Reproduced with permission of Baishideng Publishing Group, World Journal of Clinical Oncology.

Genetic Predictors Of Metabolic Side Effects Of Diuretic Therapy, Jorge L. Del Aguila

Dissertations & Theses (Open Access)

Thiazide diuretics are a recommended first-line monotherapy for hypertension (i.e.SBP>140 mmHg or DBP>90 mmHg). Even so, diuretics are associated with adverse metabolic side effects, such as hyperlipidemia, hyperglycemia and hypokalemia which increase the risk of developing type II diabetes. This thesis used three analytical strategies to identify and quantify genetic factors that contribute to the development of adverse metabolic effects due to thiazide diuretic treatment. I performed a genome-wide association study (GWAS) and meta-analysis of the change in fasting plasma glucose and triglycerides in response to HCTZ from two different clinical trials: the Pharmacogenomic Evaluation of Antihypertensive Responses …

Association Between Class Iii Obesity (Bmi Of 40-59 Kg/M2) And Mortality: A Pooled Analysis Of 20 Prospective Studies, Cari M. Kitahara, Alan J. Flint, Amy Berrington De Gonzalez, Leslie Bernstein, Michelle Brotzman, Kim Robien, +30 Additional Authors

Epidemiology Faculty Publications

Background

The prevalence of class III obesity (body mass index [BMI]≥40 kg/m2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity.

Methods and Findings

In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per …

Trends And Determinants Of Up-To-Date Status With Colorectal Cancer Screening In Tennessee, 2002-2008, Sreenivas P. Veeranki, Shimin Zheng

ETSU Faculty Works

BACKGROUND:

Screening rates for colorectal cancer (CRC) are increasing nationwide including Tennessee (TN); however, their up-to-date status is unknown. The objective of this study is to determine the trends and characteristics of TN adults who are up-to-date status with CRC screening during 2002-2008.

METHODS:

We examined data from the TN Behavioral Risk Factor Surveillance System for 2002, 2004, 2006 and 2008 to estimate the proportion of respondents aged 50 years and above who were up-to-date status with CRC screening, defined as an annual home fecal occult blood test and/or sigmoidoscopy or colonoscopy in the past 5 years. We identified trends …

Rationale, Design, And Baseline Characteristics Of A Randomized, Placebo-Controlled Cardiovascular Outcome Trial Of Empagliflozin (Empa-Reg Outcometm), Bernard Zinman, Silvio E. Inzucchi, John M. Lachin, Christoph Wanner, Roberto Ferrari, David Fitchett, Erich Bluhmki, Stefan Hantel, Joan Kempthorne-Rawson, Jennifer Newman, Odd Erik Johansen, Hans Juergen Woerle, Uli C. Broedl

Epidemiology Faculty Publications

Background

Evidence concerning the importance of glucose lowering in the prevention of cardiovascular (CV) outcomes remains controversial. Given the multi-faceted pathogenesis of atherosclerosis in diabetes, it is likely that any intervention to mitigate this risk must address CV risk factors beyond glycemia alone. The SGLT-2 inhibitor empagliflozin improves glucose control, body weight and blood pressure when used as monotherapy or add-on to other antihyperglycemic agents in patients with type 2 diabetes. The aim of the ongoing EMPA-REG OUTCOMETM trial is to determine the long-term CV safety of empagliflozin, as well as investigating potential benefits on microvascular outcomes.

Methods

Patients who …

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 …

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 …

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 …

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% …