Physical Sciences and Mathematics 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) …

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 …

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 …

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% …

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.

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 …

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 …

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 …

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% …

Metabolic Syndrome Components And Their Response To Lifestyle And Metformin Interventions Are Associated With Differences In Diabetes Risk In Persons With Impaired Glucose Tolerance, H. Florez, M. Temprosa, Trevor J. Orchard, Kieren J. Mather, Santica M. Marcovina, Elizabeth Barrett-Connor, Edward Horton, C. D. Saudek, F. X. Pi-Sunyer, R. E. Ratner, R. B. Goldberg

GW Biostatistics Center

Aims

To determine the association of metabolic syndrome (MetS) and its components with diabetes risk in participants with impaired glucose tolerance (IGT), and whether intervention-related changes in MetS lead to differences in diabetes incidence.

Methods

We used the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) revised MetS definition at baseline and intervention-related changes of its components to predict incident diabetes using Cox models in 3234 Diabetes Prevention Program (DPP) participants with IGT over an average follow-up of 3.2 years.

Results

In an intention-to-treat analysis, the demographic-adjusted hazard ratios (95% confidence interval) for diabetes in those with MetS (vs. …

Venue-Based Recruitment Of Women At Elevated Risk For Hiv: An Hiv Prevention Trials Network Study, Danielle F. Haley, Carol E. Golin, Wafaa M. El-Sadr, James P. Hughes, Jing Wang, Irene Kuo, +13 Additional Authors

Epidemiology Faculty Publications

Background: The challenge of identifying and recruiting U.S. women at elevated risk for HIV acquisition impedes prevention studies and services. HIV Prevention Trials Network (HPTN) 064 was a U.S. multisite, longitudinal cohort study designed to estimate HIV incidence among women living in communities with prevalent HIV and poverty. Venue-based sampling (VBS) methodologies and participant and venue characteristics are described.

Methods: Eligible women were recruited from 10 U.S. communities with prevalent HIV and poverty using VBS. Participant eligibility criteria included age 18–44 years, residing in a designated census tract/zip code, and self-report of at least one high-risk personal and/or male sexual …

The Impact Of Salsalate Treatment On Serum Levels Of Advanced Glycation End Products In Type 2 Diabetes., Joshua I Barzilay, Kathleen A. Jablonski, Vivian Fonseca, Steven E Shoelson, Allison B Goldfine, Christopher Strauch, Vincent M Monnier, Tinsal-T2d Research Consortium.

GW Biostatistics Center

OBJECTIVE Salsalate is a nonacetylated salicylate that lowers glucose levels in people with type 2 diabetes (T2D). Here we examined whether salsalate also lowered serum-protein-bound levels of early and advanced glycation end products (AGEs) that have been implicated in diabetic vascular complications. RESEARCH DESIGN AND METHODS Participants were from the Targeting Inflammation Using Salsalate for Type 2 Diabetes (TINSAL-T2D) study, which examined the impact of salsalate treatment on hemoglobin A1c (HbA1c) and a wide variety of other parameters. One hundred eighteen participants received salsalate, 3.5 g/day for 48 weeks, and 109 received placebo. Early glycation product levels (HbA1c and fructoselysine …

Genetic Risk Of Progression To Type 2 Diabetes And Response To Intensive Lifestyle Or Metformin In Prediabetic Women With And Without A History Of Gestational Diabetes Mellitus., Shannon D Sullivan, Kathleen A. Jablonski, Jose C Florez, Dana Dabelea, Paul W Franks, Sam Dagogo-Jack, Catherine Kim, William C Knowler, Costas A Christophi, Robert Ratner, Diabetes Prevention Program Research Group.

GW Biostatistics Center

OBJECTIVE The Diabetes Prevention Program (DPP) trial investigated rates of progression to diabetes among adults with prediabetes randomized to treatment with placebo, metformin, or intensive lifestyle intervention. Among women in the DPP, diabetes risk reduction with metformin was greater in women with prior gestational diabetes mellitus (GDM) compared with women without GDM but with one or more previous live births.

RESEARCH DESIGN AND METHODS We asked if genetic variability could account for these differences by comparing β-cell function and genetic risk scores (GRS), calculated from 34 diabetes-associated loci, between women with and without histories of GDM.

RESULTS β-Cell function was …

Concomitant Socioeconomic, Behavioral, And Biological Factors Associated With The Disproportionate Hiv Infection Burden Among Black Men Who Have Sex With Men In 6 U.S. Cities, Kenneth H. Mayer, Lei Wang, Beryl A. Koblin, Sharon B. Mannheimer, Manya Magnus, +13 Additional Authors

Epidemiology Faculty Publications

Background

American Black men who have sex with men (MSM) are disproportionately affected by HIV, but the factors associated with this concentrated epidemic are not fully understood.

Methods

Black MSM were enrolled in 6 US cities to evaluate a multi-component prevention intervention, with the current analysis focusing on the correlates of being newly diagnosed with HIV compared to being HIV-uninfected or previously diagnosed with HIV.

Results

HPTN 061 enrolled 1553 Black MSM whose median age was 40; 30% self-identified exclusively as gay or homosexual, 29% exclusively as bisexual, and 3% as transgender. About 1/6th(16.2%) were previously diagnosed with HIV (PD); …

Analysis Of Schizophrenia Data Using A Nonlinear Threshold Index Logistic Model., Zhenyu Jiang, Chengan Du, Assen Jablensky, Hua Liang, Zudi Lu, Yang Ma, Kok Lay Teo

GW Biostatistics Center

Genetic information, such as single nucleotide polymorphism (SNP) data, has been widely recognized as useful in prediction of disease risk. However, how to model the genetic data that is often categorical in disease class prediction is complex and challenging. In this paper, we propose a novel class of nonlinear threshold index logistic models to deal with the complex, nonlinear effects of categorical/discrete SNP covariates for Schizophrenia class prediction. A maximum likelihood methodology is suggested to estimate the unknown parameters in the models. Simulation studies demonstrate that the proposed methodology works viably well for moderate-size samples. The suggested approach is therefore …

Community Colleges And Public Health: An Integral Part Of The Continuum Of Education For Public Health, Richard Riegelman, Cynthia Wilson

Epidemiology Faculty Publications

No abstract provided.

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% …

Short And Long-Term Lifestyle Coaching Approaches Used To Address Diverse Participant Barriers To Weight Loss And Physical Activity Adherence, Elizabeth M. Venditti, Judith Wylie-Rosett, Linda M. Delahanty, Lisa L. Mele, Mary A. Hoskin, Sharon Edelstein

GW Biostatistics Center

Background

Individual barriers to weight loss and physical activity goals in the Diabetes Prevention Program, a randomized trial with 3.2 years average treatment duration, have not been previously reported. Evaluating barriers and the lifestyle coaching approaches used to improve adherence in a large, diverse participant cohort can inform dissemination efforts.

Methods

Lifestyle coaches documented barriers and approaches after each session (mean session attendance = 50.3 +/- 21.8). Subjects were 1076 intensive lifestyle participants (mean age = 50.6 years; mean BMI = 33.9 kg/m2; 68% female, 48% non-Caucasian). Barriers and approaches used to improve adherence were ranked by the percentage of …

Engagement With Care, Substance Use, And Adherence To Therapy In Hiv/Aids, Patrice K. Nicholas, Suzanne Willard, Clinton J. Thompson, Carol Dawson-Rose, Inge B. Corless, +20 Additional Authors

GW Biostatistics Center

Engagement with care for those living with HIV is aimed at establishing a strong relationship between patients and their health care provider and is often associated with greater adherence to therapy and treatment (Flickinger, Saha, Moore, and Beach, 2013). Substance use behaviors are linked with lower rates of engagement with care and medication adherence (Horvath, Carrico, Simoni, Boyer, Amico, and Petroli, 2013). This study is a secondary data analysis using a cross-sectional design from a larger randomized controlled trial (n = 775) that investigated the efficacy of a self-care symptom management manual for participants living with HIV. Participants were …

Cardiometabolic Risk Assessments By Body Mass Index Z-Score Or Waist-To-Height Ratio In A Multiethnic Sample Of Sixth-Graders, Henry S. Kahn, Laure El Ghormli, Russell Jago, Gary D. Foster, Robert G. Mcmurray, John B. Buse, Diane D. Stadler, Roberto P. Trevino, Tom Baranowski, Healthy Study Group

GW Biostatistics Center

Convention defines pediatric adiposity by the body mass index -score (BMIz) referenced to normative growth charts. Waist-to-height ratio (WHtR) does not depend on sex-and-age references. In the HEALTHY Study enrollment sample, we compared BMIz with WHtR for ability to identify adverse cardiometabolic risk. Among 5,482 sixth-grade students from 42 middle schools, we estimated explanatory variations (R²) and standardized beta coefficients of BMIz or WHtR for cardiometabolic risk factors: insulin resistance (HOMA-IR), lipids, blood pressures, and glucose. For each risk outcome variable, we prepared adjusted regression models for four subpopulations stratified by sex and high versus lower fatness. …

Mediation Analysis Of Gestational Age, Congenital Heart Defects, And Infant Birth-Weight, Adane Wogu, Christopher 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) …