Biostatistics Commons^™

A Unification Of Mediation And Interaction: A Four-Way Decomposition, Tyler J. Vanderweele

Harvard University Biostatistics Working Paper Series

It is shown that the overall effect of an exposure on an outcome, in the presence of a mediator with which the exposure may interact, can be decomposed into four components: (i) the effect of the exposure in the absence of the mediator, (ii) the interactive effect when the mediator is left to what it would be in the absence of exposure, (iii) a mediated interaction, and (iv) a pure mediated effect. These four components, respectively, correspond to the portion of the effect that is due to neither mediation nor interaction, to just interaction (but not mediation), to both mediation …

New Malignancies After Squamous Cell Carcinoma And Melanomas: A Population-Based Study From Norway, Trude E. Robsahm, Margaret R. Karagas, Judy R. Rees, Astri Syse

Dartmouth Scholarship

Skin cancer survivors experience an increased risk for subsequent malignancies but the associated risk factors are poorly understood. This study examined the risk of a new primary cancer following an initial skin cancer and assessed risk factors associated with second primary cancers.

The Association Of Calcium Intake And Other Risk Factors With Cardiovascular Disease Among Obese Adults In Usa, Yang Chen, Sheryl Strasser, Katie Callahan, David Blackley, Yan Cao, Liang Wang, Shimin Zheng

ETSU Faculty Works

In this study, we used a cross-sectional study design to examine the relationship between the calcium intake and risk factors for CVD among obese adults by using continuous waves of National Health and Nutrition Examination Survey (NHANES) data 1999-2010. The association between calcium intake and risk factors of CVD (hypertension, total cholesterol, HDL, glycohemoglobin), CRP, albuminuria) is assessed among obese adults in USA. The incidence of Cardiovascular Disease (CVD) is high among obese people. The potential effects of inadequate calcium intake on CVD are receiving increased epidemiologic attention. Understanding the association between risk factors for CVD and calcium intake among …

Adaptive Pair-Matching In The Search Trial And Estimation Of The Intervention Effect, Laura Balzer, Maya L. Petersen, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

In randomized trials, pair-matching is an intuitive design strategy to protect study validity and to potentially increase study power. In a common design, candidate units are identified, and their baseline characteristics used to create the best n/2 matched pairs. Within the resulting pairs, the intervention is randomized, and the outcomes measured at the end of follow-up. We consider this design to be adaptive, because the construction of the matched pairs depends on the baseline covariates of all candidate units. As consequence, the observed data cannot be considered as n/2 independent, identically distributed (i.i.d.) pairs of units, as current practice assumes. …

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); …

Estimating Population Treatment Effects From A Survey Sub-Sample, Kara E. Rudolph, Ivan Diaz, Michael Rosenblum, Elizabeth A. Stuart

Johns Hopkins University, Dept. of Biostatistics Working Papers

We consider the problem of estimating an average treatment effect for a target population from a survey sub-sample. Our motivating example is generalizing a treatment effect estimated in a sub-sample of the National Comorbidity Survey Replication Adolescent Supplement to the population of U.S. adolescents. To address this problem, we evaluate easy-to-implement methods that account for both non-random treatment assignment and a non-random two-stage selection mechanism. We compare the performance of a Horvitz-Thompson estimator using inverse probability weighting (IPW) and two double robust estimators in a variety of scenarios. We demonstrate that the two double robust estimators generally outperform IPW in …

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 …

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) …

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 …

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 …

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. …

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% …

Primary Care-Based Educational Interventions To Decrease Risk Factors For Metabolic Syndrome For Adults With Major Psychotic And/Or Affective Disorders: A Systematic Review, Cynthia Nover, Sarah S. Jackson

Epidemiology Faculty Publications

Background

Individuals with major psychotic and/or affective disorders are at increased risk for developing metabolic syndrome due to lifestyle- and treatment-related factors. Numerous pharmacological and non-pharmacological interventions have been tested in inpatient and outpatient mental health settings to decrease these risk factors. This review focuses on primary care-based non-pharmacological (educational or behavioral) interventions to decrease metabolic syndrome risk factors in adults with major psychotic and/or affective disorders.

Methods

The authors conducted database searches of PsychINFO, MEDLINE and the Cochrane Database of Systematic Reviews, as well as manual searches and gray literature searches to identify included studies.

Results

The authors were …

Multiple Hypotheses Testing Procedures In Clinical Trials And Genomic Studies, Qing Pan

Epidemiology Faculty Publications

We review and compare multiple hypothesis testing procedures used in clinical trials and those in genomic studies. Clinical trials often employ global tests, which draw an overall conclusion for all the hypotheses, such as SUM test, Two-Step test, Approximate Likelihood Ratio test (ALRT), Intersection-Union Test (IUT), and MAX test. The SUM and Two-Step tests are most powerful under homogeneous treatment effects, while the ALRT and MAX test are robust in cases with non-homogeneous treatment effects. Furthermore, the ALRT is robust to unequal sample sizes in testing different hypotheses. In genomic studies, stepwise procedures are used to draw marker-specific conclusions and …

Targeting Inflammation Using Salsalate In Patients With Type 2 Diabetes: Effects On Flow-Mediated Dilation (Tinsal-Fmd)., Allison B Goldfine, J Stewart Buck, Cyrus Desouza, Vivian Fonseca, Yii-Der Ida Chen, Steven E Shoelson, Kathleen A. Jablonski, Mark A Creager, The Tinsal-Fmd Team

GW Biostatistics Center

OBJECTIVE: To test whether inhibiting inflammation with salsalate improves endothelial function in patients with type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS: We conducted an ancillary study to the National Institutes of Health-sponsored, multicenter, randomized, double-masked, placebo-controlled trial evaluating the safety and efficacy of salsalate in targeting inflammation to improve glycemia in patients with T2D. Flow-mediated, endothelium-dependent dilation (FMD) and endothelium-independent, nitroglycerin-mediated dilation (NMD) of the brachial artery were assessed at baseline and 3 and 6 months following randomization to either salsalate 3.5 g/day or placebo. The primary end point was change in FMD at 6 months.

RESULTS: A total …

Factors Associated With Parental Decision Making And Childhood Vaccination, Zuwen Qiu-Shultz

UNLV Theses, Dissertations, Professional Papers, and Capstones

In order to better understand factors affecting immunization status, logistic regression was used to assess the association of various socio-demographic factors and whether parents would have their child immunized if not a state mandate. Factors included in the study were race, household income, number of children in the household, number of adults in the household, if the child had a primary provider, if the child had a health check-up in the last twelve months, and medical insurance status of the child. The combined Nevada Kindergarten Health Survey Result of 2009-2010 (Year Two) and 2010-2011 (Year Three) conducted by the Nevada …

Molecular Detection Of Culture-Confirmed Bacterial Bloodstream Infections With Limited Enrichment Time, Miranda S. Moore, Chase D. Mccann, Jeanne Jordan

Epidemiology Faculty Publications

Conventional blood culturing using automated instrumentation with phenotypic identification requires a significant amount of time to generate results. This study investigated the speed and accuracy of results generated using PCR and pyrosequencing compared to the time required to obtain Gram stain results and final culture identification for cases of culture-confirmed bloodstream infections. Research and physician-ordered blood cultures were drawn concurrently. Aliquots of the incubating research blood culture fluid were removed hourly between 5 and 8 h, at 24 h, and again at 5 days. DNA was extracted from these 6 time point aliquots and analyzed by PCR and pyrosequencing for …

Associations Of Smoking Status And Serious Psychological Distress With Chronic Obstructive Pulmonary Disease, Ke-Sheng Wang, Liang Wang, Shimin Zheng, Long-Yang Wu

ETSU Faculty Works

Background: Chronic obstructive pulmonary disease (COPD) has been a major public health problem due to its high prevalence, morbidity, and mortality. Smoking is a major risk factor for COPD, while serious psychological distress (SPD) is prevalent among COPD patients. However, no study focusing on the effect of SPD on COPD has been so far conducted, while few studies have focused on the associations of SPD and behavioral factors with COPD by smoking status.

Objectives: This study aimed to examine the associations of SPD and behavioral factors (such as smoking and physical activity) with COPD.

Materials and Methods: Weighted logistic regression …

Never Smokers -- Are They More Sensitive To The Respiratory Health Effects Of Ambient Air Pollution?, Zuhair Saleh Natto

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Several studies show an association between ambient particulate matter (PM) and all-cause mortality. The Adventist Health and Smog 1 (AHSMOG-1) study (N=6,338) has previously found associations between ambient air pollution and incident chronic obstructive pulmonary disease (COPD) using the spatial interpolation method from the three nearest fixed monitoring stations to residence and workplace. However, few studies have assessed the risk of death among disease specific subgroups such as those with COPD.

Objectives: The aims of this study were 1) to assess the effect of chronic exposure to ambient air pollutants on risk of all-cause mortality among persons with COPD …

Overcoming Shortage Of Pharmacists To Provide Pharmaceutical Services In Public Health Centers In Indonesia, Yuyun Yuniar, Max Joseph Herman

Kesmas

Indonesia masih menghadapi keterbatasan jumlah apoteker di puskesmas, sehingga pihak pemerintah daerah dan puskesmas harus berupaya mengatasi permasalahan tersebut. Penelitian ini bertujuan untuk menggambarkan ketersediaan dan distribusi tenaga pelayanan kefarmasian di puskesmas serta permasalahan dan alternatif pemecahannya. Data diambil dari hasil Riset Fasilitas Kesehatan (Rifaskes) tahun 2011I. Data kuantitatif tentang tenaga pelayanan kefarmasian di puskesmas dianalisis secara deskriptif berdasarkan regional. Data kualitatif sebagai pendukung diperoleh melalui wawancara mendalam dengan bagian kepegawaian dinas kesehatan dan apoteker empat puskesmas di Kota Bogor dan Bekasi, 3 kemudian dianalisis dengan metode analisis tema. Hasil analisis menunjukkan bahwa Sulawesi memiliki persentase puskesmas dengan tenaga apoteker …

Plasma S-Adenosylmethionine, Dnmt Polymorphisms, And Peripheral Blood Line-1 Methylation Among Healthy Chinese Adults In Singapore, Maki Inoue-Choi, Heather H. Nelson, Kim Robien, Erland Arning, Teodoro Bottiglieri, Woon-Puay Koh, Jian-Min Yuan

Epidemiology Faculty Publications

Background

Global hypomethylation of repetitive DNA sequences is believed to occur early in tumorigenesis. There is a great interest in identifying factors that contribute to global DNA hypomethylation and associated cancer risk. We tested the hypothesis that plasma S-adenosylmethionine (SAM) level alone or in combination with genetic variation in DNA methyltransferases (DNMT1, DNMT3A andDNMT3B) was associated with global DNA methylation extent at long interspersed nucleotide element-1 (LINE-1) sequences.

Methods

Plasma SAM level and LINE-1 DNA methylation index were measured using stored blood samples collected from 440 healthy Singaporean Chinese adults during 1994-1999. Genetic polymorphisms of …

Correlates Of Hiv Acquisition In A Cohort Of Black Men Who Have Sex With Men In The United States: Hiv Prevention Trials Network (Hptn) 061, Beryl A. Koblin, Kenneth H. Mayer, Susan H. Eshleman, Lei Wang, Sharon B. Mannheimer, Carlos Del Rio, Steve Shoptaw, Manya Magnus, Susan Buchbinder, Leo Wilton, Ting-Yuan Liu, Vanessa Cummings, Estelle Piwowar-Manning, Sheldon D. Fields, Sam Griffith, Vanessa Elharrar, Darrell Wheeler

Epidemiology Faculty Publications

Background

Black men who have sex with men (MSM) in the United States (US) are affected by HIV at disproportionate rates compared to MSM of other race/ethnicities. Current HIV incidence estimates in this group are needed to appropriately target prevention efforts.

Methods

From July 2009 to October 2010, Black MSM reporting unprotected anal intercourse with a man in the past six months were enrolled and followed for one year in six US cities for a feasibility study of a multi-component intervention to reduce HIV infection. HIV incidence based on HIV seroconversion was calculated as number of events/100 person-years. Multivariate proportional …

Attributing Effects To Interactions, Tyler J. Vanderweele, Eric J. Tchetgen Tchetgen

Harvard University Biostatistics Working Paper Series

A framework is presented which allows an investigator to estimate the portion of the effect of one exposure that is attributable to an interaction with a second exposure. We show that when the two exposures are independent, the total effect of one exposure can be decomposed into a conditional effect of that exposure and a component due to interaction. The decomposition applies on difference or ratio scales. We discuss how the components can be estimated using standard regression models, and how these components can be used to evaluate the proportion of the total effect of the primary exposure attributable to …

Cardiovascular Outcome Trials In Type 2 Diabetes And The Sulphonylurea Controversy: Rationale For The Active-Comparator Carolina Trial, Julio Rosenstock, Nikolaus Marx, Steven E. Kahn, Bernard Zinman, John J. Kastelein, John M. Lachin, Erich Bluhmki, Sanjay Patel, Odd-Erik Johansen, Hans-Jurgen Woerle

Epidemiology Faculty Publications

Sulphonylureas (SUs) are widely used glucose-lowering agents in type 2 diabetes mellitus (T2DM) with apparent declining efficacy over time. Concerns have been raised from observational retrospective studies on the cardiovascular (CV) safety of SUs but there are few long-term data on CV outcomes from randomized controlled trials (RCTs) involving the use of this class of agents. Most of the observational studies and registry data are conflicting and vary with study population and methodology used for analyses. To address the SU controversy, we reviewed the recently published literature (until end of the year 2011) to evaluate the impact of SUs on …

When To Start Antiretroviral Therapy: The Need For An Evidence Base During Early Hiv Infection, James D. Lundgren, Abdel G. Babiker, Fred M. Gordin, Alvaro H. Borges, James D. Neaton

Epidemiology Faculty Publications

Background

Strategies for use of antiretroviral therapy (ART) have traditionally focused on providing treatment to persons who stand to benefit immediately from initiating the therapy. There is global consensus that any HIV+ person with CD4 counts less than 350 cells/μl should initiate ART. However, it remains controversial whether ART is indicated in asymptomatic HIV-infected persons with CD4 counts above 350 cells/μl, or whether it is more advisable to defer initiation until the CD4 count has dropped to 350 cells/μl. The question of when the best time is to initiate ART during early HIV infection has always been vigorously debated. The …

Association Between Adverse Childhood Experiences And Diagnosis Of Cancer, Monique J. Brown, Leroy R. Thacker, Steven A. Cohen

Faculty Publications

Objective: Adverse childhood experiences (ACEs) are linked to multiple adverse health outcomes. This study examined the association between ACEs and cancer diagnosis.

Methods: Data from the 2010 Behavioral Risk Factor Surveillance System (BRFSS) survey were used. The BRFSS is the largest ongoing telephone health survey, conducted in all US states, the District of Columbia, Puerto Rico, Guam and the U.S. Virgin Islands, and provides data on a variety of health issues among the non-institutionalized adult population. Principal component analysis (PCA) was used to derive components for ACEs. Multivariable logistic regression models were used to provide adjusted odds ratios (OR) and …

Estimating Effects On Rare Outcomes: Knowledge Is Power, Laura B. Balzer, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Many of the secondary outcomes in observational studies and randomized trials are rare. Methods for estimating causal effects and associations with rare outcomes, however, are limited, and this represents a missed opportunity for investigation. In this article, we construct a new targeted minimum loss-based estimator (TMLE) for the effect of an exposure or treatment on a rare outcome. We focus on the causal risk difference and statistical models incorporating bounds on the conditional risk of the outcome, given the exposure and covariates. By construction, the proposed estimator constrains the predicted outcomes to respect this model knowledge. Theoretically, this bounding provides …

Linking And Retaining Hiv Patients In Care: The Importance Of Provider Attitudes And Behaviors, Manya Magnus, Jane Herwehe, Michelli Murtaza-Rossini, Petera Reine, Damien Cuffie, Deann Gruber, Michael Kaiser

Epidemiology Faculty Publications

Retention in HIV treatment may reduce morbidity and mortality, as well as slow the epidemic. Myriad barriers to retention include stigma, homophobia, structural barriers, transportation, and insurance. The purpose of this study was to evaluate patient perceptions of provider attitudes among HIV-infected persons within a state-wide public hospital system in Louisiana. A convenience sample of patients attending HIV clinics throughout the state participated in an anonymous interview. Factors associated with negative perceptions of care were evaluated in conjunction with a validated stigma measure. Factors associated with having a delayed entry into or break in care were evaluated in conjunction with …

Progress Realized: Trends In Hiv-1 Viral Load And Cd4 Cell Count In A Tertiary-Care Center From 1999 Through 2011, Howard B. Gale, Manuel D. Rodriguez, Heather J. Hoffman, Debra A. Benator, Fred M. Gordin, Ann M. Labriola, Virginia L. Kan

Epidemiology Faculty Publications

Abstract

Accumulating evidence suggests that alterations in immune function may be important in the etiology of papillary thyroid cancer (PTC). To identify genetic markers in immune-related pathways, we evaluated 3,985 tag single nucleotide polymorphisms (SNPs) in 230 candidate gene regions (adhesion-extravasation-migration, arachidonic acid metabolism/eicosanoid signaling, complement and coagulation cascade, cytokine signaling, innate pathogen detection and antimicrobials, leukocyte signaling, TNF/NF-kB pathway or other) in a case-control study of 344 PTC cases and 452 controls. We used logistic regression models to estimate odds ratios (OR) and calculate one degree of freedom P values of linear trend (PSNP-trend) for the association …