Biostatistics Commons^™

Causal Mediation In A Survival Setting With Time-Dependent Mediators, Wenjing Zheng, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

The effect of an expsore on an outcome of interest is often mediated by intermediate variables. The goal of causal mediation analysis is to evaluate the role of these intermediate variables (mediators) in the causal effect of the exposure on the outcome. In this paper, we consider causal mediation of a baseline exposure on a survival (or time-to-event) outcome, when the mediator is time-dependent. The challenge in this setting lies in that the event process takes places jointly with the mediator process; in particular, the length of the mediator history depends on the survival time. As a result, we argue …

On Identification Of Natural Direct Effects When A Confounder Of The Mediator Is Directly Affected By Exposure, Eric J. Tchetgen Tchetgen, Tyler J. Vanderweele

COBRA Preprint Series

Natural direct and indirect effects formalize traditional notions of mediation analysis into a rigorous causal framework and have recently received considerable attention in epidemiology and in the social sciences. Sufficient conditions for identification of natural direct effects were formulated by Judea Pearl under a nonparametric structural equations model, which assumes certain independencies between potential outcomes. A common situation in epidemiology is that a confounder of the mediator is affected by the exposure, in which case, natural direct effects fail to be nonparametrically identified without additional assumptions, even under Pearl's nonparametric structural equations model. In this paper, the authors show that …

Selective Impact Of Hiv Disease Progression On The Innate Immune System In The Human Female Reproductive Tract., Timothy Lahey, Mimi Ghosh, John V. Fahey, Zheng Sheng, Lucy R. Mukura, Yan Song, Susan Cu-Uvin, Kenneth H. Mayer, Peter F. Wright, John C. Kappes, Christina Ochsenbauer, Charles R. Wira

Epidemiology Faculty Publications

Background

We have previously demonstrated intrinsic anti-HIV activity in cervicovaginal lavage (CVL) from HIV-infected women with high CD4 counts and not on antiretroviral therapy. However, the impact of HIV disease progression on CVL innate immune responses has not been delineated.

Methods

CVL from 57 HIV-infected women not on antiretroviral therapy were collected by washing the cervicovaginal area with 10 ml of sterile normal saline. We characterized subject HIV disease progression by CD4 count strata: >500 cells/µl, 200–500 cells/µl, or <200 cells/µl of blood. To assess CVL anti-HIV activity, we incubated TZM-bl cells with HIV plus or minus CVL. Antimicrobials, cytokines, chemokines and anti-gp160 HIV IgG antibodies were measured by ELISA and Luminex.

Results

CVL exhibited broad anti-HIV activity against multiple laboratory-adapted and transmitted/founder (T/F) viruses, with anti-HIV activity ranging from 0 to 100% …

Adaptive Randomization Designs, Jenna Colavincenzo

Statistics

Adaptive design methodologies use prior information to develop a clinical trial design. The goal of an adaptive design is to maintain the integrity and validity of the study while giving the researcher flexibility in identifying the optimal treatment. An example of an adaptive design can be seen in a basic pharmaceutical trial. There are three phases of the overall trial to compare treatments and experimenters use the information from the previous phase to make changes to the subsequent phase before it begins.

Adaptive design methods have been in practice since the 1970s, but have become increasingly complex ever since. One …

Predictors Of Hypertension And Prehypertension In Cal Poly Students, Toria Mock

Statistics

This study analyzed predictors of hypertension and prehypertension in Cal Poly students. Hypertension and prehypertension are known to increase the risk of blood clots, plaque buildup, and tissue/organ damage from blocked arteries. Researching predictors of hypertension and prehypertension can help to determine methods of minimizing the probability of hypertension and prehypertension in a patient. Data from the FLASH study was used to analyze associations between possible predictor variables, such as stress and physical activity, and hypertension/prehypertension. BMI, bodyfat, and the interaction between videogames per weekend day and gender were found to be significantly associated with hypertension and prehypertension in Cal …

Change-Point Analysis Of Paired Allele-Specific Copy Number Variation Data, Yinglei Lai

GW Biostatistics Center

The recent genome-wide allele-specific copy number variation data enable us to explore two types of genomic information including chromosomal genotype variations as well as DNA copy number variations. For a cancer study, it is common to collect data for paired normal and tumor samples. Then, two types of paired data can be obtained to study a disease subject. However, there is a lack of methods for a simultaneous analysis of these four sequences of data. In this study, we propose a statistical framework based on the change-point analysis approach. The validity and usefulness of our proposed statistical framework are demonstrated …

Characteristics Of Children With Type 1 Diabetes And Persistent Suboptimal Glycemic Control., Hyuntae Kim, Angelo Elmi, Celia L. Henderson, Fran R. Cogen, Paul B. Kaplowitz

Epidemiology Faculty Publications

Objective: This study aims to determine the relationship between the duration of persistent poor glycemic control in type 1 diabetes mellitus (T1DM) children and the likelihood of subsequent improvement.

Methods: A retrospective cohort study was conducted on T1DM patients aged 6-18 years, followed for at least six visits at Children’s National Medical Center (Washington, DC) with at least one hemoglobin A1c (HbA1c) ≥10% after the first year since the initial visit (n=151). Medical records of patients with subsequently improved glycemic control were reviewed (n=39).

Results: Patients aged 12-18 years, females, and Medicaid patients were twice as likely to be in …

Unbiased Estimation For The Contextual Effect Of Duration Of Adolescent Height Growth On Adulthood Obesity And Health Outcomes Via Hierarchical Linear And Nonlinear Models, Robert Carrico

Theses and Dissertations

This dissertation has multiple aims in studying hierarchical linear models in biomedical data analysis. In Chapter 1, the novel idea of studying the durations of adolescent growth spurts as a predictor of adulthood obesity is defined, established, and illustrated. The concept of contextual effects modeling is introduced in this first section as we study secular trend of adulthood obesity and how this trend is mitigated by the durations of individual adolescent growth spurts and the secular average length of adolescent growth spurts. It is found that individuals with longer periods of fast height growth in adolescence are more prone to …

Families Or Unrelated: The Evolving Debate In Genetic Association Studies, David W. Fardo, Richard Charnigo, Michael P. Epstein

Biostatistics Faculty Publications

To help uncover the genetic determinants of complex disease, a scientist often designs an association study using either unrelated subjects or family members within pedigrees. But which of these two subject recruitment paradigms is preferable? This editorial addresses the debate over the relative merits of family- and population-based genetic association studies. We begin by briefly recounting the evolution of genetic epidemiology and the rich crossroads of statistics and genetics. We then detail the arguments for the two aforementioned paradigms in recent and current applications. Finally, we speculate on how the debate may progress with the emergence of next-generation sequencing technologies.

Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit

Dartmouth Scholarship

There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls.

Why Odds Ratio Estimates Of Gwas Are Almost Always Close To 1.0, Yutaka Yasui

COBRA Preprint Series

“Missing heritability” in genome-wide association studies (GWAS) refers to the seeming inability for GWAS data to capture the great majority of genetic causes of a disease in comparison to the known degree of heritability for the disease, in spite of GWAS’ genome-wide measures of genetic variations. This paper presents a simple mathematical explanation for this phenomenon, assuming that the heritability information exists in GWAS data. Specifically, it focuses on the fact that the great majority of association measures (in the form of odds ratios) from GWAS are consistently close to the value that indicates no association, explains why this occurs, …

Analyzing Multiple Independent Spatial Point Processes, Neal Grantham

Statistics

No abstract provided.

Differential Patterns Of Interaction And Gaussian Graphical Models, Masanao Yajima, Donatello Telesca, Yuan Ji, Peter Muller

COBRA Preprint Series

We propose a methodological framework to assess heterogeneous patterns of association amongst components of a random vector expressed as a Gaussian directed acyclic graph. The proposed framework is likely to be useful when primary interest focuses on potential contrasts characterizing the association structure between known subgroups of a given sample. We provide inferential frameworks as well as an efficient computational algorithm to fit such a model and illustrate its validity through a simulation. We apply the model to Reverse Phase Protein Array data on Acute Myeloid Leukemia patients to show the contrast of association structure between refractory patients and relapsed …

Automated Diagnoses Of Attention Deficit Hyperactive Disorder Using Magnetic Resonance Imaging, Ani Eloyan, John Muschelli, Mary Beth Nebel, Han Liu, Fang Han, Tuo Zhao, Anita Barber, Suresh Joel, James J. Pekar, Stewart Mostofsky, Brian Caffo

Johns Hopkins University, Dept. of Biostatistics Working Papers

Successful automated diagnoses of attention de.cit hyperactive disorder (ADHD) using imaging and functional biomarkers would have fundamental consequences on the public health impact of the disease. In this work, we show results on the predictability of ADHD using imaging biomarkers and discuss the scienti.c and diagnostic impacts of the research. We created a prediction model using the land­mark ADHD 200 data set focusing on resting state functional connectivity (rs-fc) and structural brain imaging. We predicted ADHD status and subtype, obtained by behavioral examination, using imaging data, intelligence quotients and other co­variates. The novel contributions of this manuscript include a thorough …

Perbandingan Tingkat Kepuasan Kerja Perawat Dan Kepuasan Pasien, Jamilla Upik Noras, Ratu Ayu Dewi Sartika

Kesmas

Perawat adalah ujung tombak pemberi pelayanan langsung pada pasien selama 24 jam. Tujuan penelitian adalah untuk membandingkan tingkat kepuasan kerja perawat dengan kepuasan pasien terhadap pelayanan keperawatan kelas 3 di Rumah Sakit Umum Pusat (RSUP) X Jakarta. Penelitian ini bersifat deskriptif dengan desain studi cross sectional, pendekatan kuantitatif dan kualitatif. Populasi adalah seluruh perawat yang bertugas sebagai pelaksana keperawatan kelas 3 sebanyak 40 orang ser- ta pasien yang dirawat di ruang rawat inap kelas 3 sebanyak 120 orang. Pengambilan sampel dilakukan secara purposive sampling sesuai dengan kriteria inklusi dan ekslusi. Hasil pengukuran kuantitatif menunjukkan bah- wa tingkat kepuasan kerja perawat …

Demographics And Survival Of Aids Cases With Cancer, Washington, Dc, 1996-2006, Heather A. Young, Eric Engels, Anne-Marie Sufian-Kargbo, Alicia Vargas, Kathleen Rogers, Tiffany West, Amanda D. Castel

Epidemiology Faculty Publications

Background

Washington, DC (DC) has one of the highest HIV/AIDS rates in the U.S and cancer is the second leading cause of death among DC residents. This study sought to examine the demographic characteristics and survival of persons with AIDS defining cancers (ADCs) compared to those with non-AIDS defining cancers (NADCs) between the early HAART era (1996-2001) and the late HAART era (2002-2006) in DC.

Methods

Cases reported from 1996-2006 to the DC Cancer Registry and the AIDS Surveillance Registry were linked using a probabilistic matching algorithm. Cases were included if the cancer occurred from 4 months to 60 months …

High And Persistent Hiv Seroincidence In Men Who Have Sex With Men Across 47 U.S. Cities, Marta-Louise Ackers, Alan E. Greenberg, Carol Y. Lin, Bradford N. Bartholow, Adrian Hirsch Goodman, Michael Longhi, Marc Gurwith

Epidemiology Faculty Publications

Objective

To provide HIV seroincidence data among men who have sex with men (MSM) in the United States and to identify predictive factors for seroconversion.

Methods

From 1998–2002, 4684 high-risk MSM, age 18–60 years, participated in a randomized, placebo-controlled HIV vaccine efficacy trial at 56 U.S. clinical trial sites. Demographics, behavioral data, and HIV status were assessed at baseline and 6 month intervals. Since no overall vaccine efficacy was detected, data were combined from both trial arms to calculate HIV incidence based on person-years (py) of follow-up. Predictors of seroconversion, adjusted hazards ratio (aHR), were evaluated using a Cox proportional …

Genetic Association Studies Of Copy-Number Variation: Should Assignment Of Copy Number States Precede Testing?, Patrick Breheny, Prabhakar Chalise, Anthony Batzler, Liewei Wang, Brooke L. Fridley

Biostatistics Faculty Publications

Recently, structural variation in the genome has been implicated in many complex diseases. Using genomewide single nucleotide polymorphism (SNP) arrays, researchers are able to investigate the impact not only of SNP variation, but also of copy-number variants (CNVs) on the phenotype. The most common analytic approach involves estimating, at the level of the individual genome, the underlying number of copies present at each location. Once this is completed, tests are performed to determine the association between copy number state and phenotype. An alternative approach is to carry out association testing first, between phenotype and raw intensities from the SNP array …

Testing For Improvement In Prediction Model Performance, Margaret S. Pepe Phd, Kathleen F. Kerr, Gary M. Longton, Zheyu Wang

UW Biostatistics Working Paper Series

New methodology has been proposed in recent years for evaluating the improvement in prediction performance gained by adding a new predictor, Y, to a risk model containing a set of baseline predictors, X, for a binary outcome D. We prove theoretically that null hypotheses concerning no improvement in performance are equivalent to the simple null hypothesis that the coefficient for Y is zero in the risk model, P(D = 1|X, Y ). Therefore, testing for improvement in prediction performance is redundant if Y has already been shown to be a risk factor. We investigate properties of tests through simulation studies, …

Progestogens To Prevent Preterm Birth In Twin Pregnancies: An Individual Participant Data Meta-Analysis Of Randomized Trials., Ewoud Schuit, Sarah Stock, Rolf H.H. Groenwold, Kimberly Maurel, C. Andrew Combs, Thomas Garite, Catherine Y. Spong, Elizabeth A. Thom, Dwight J. Rouse, Steve N. Caritis, George Saade, Julia M. Zachary, Jane E. Norman, Line Rode, Katharina Klein, Ann Tabor, Elcin Cetingoz, John C. Morrison, Everett F. Magann, Christian M. Briery, Vicente Serra, Alfredo Perales, Juan Meseguer, Anwar Nassar, Arianne C. Lim, Karel G.M. Moons, Anneke Kwee, Ben W.J. Mol

Epidemiology Faculty Publications

Background

Preterm birth is the principal factor contributing to adverse outcomes in multiple pregnancies. Randomized controlled trials of progestogens to prevent preterm birth in twin pregnancies have shown no clear benefits. However, individual studies have not had sufficient power to evaluate potential benefits in women at particular high risk of early delivery (for example, women with a previous preterm birth or short cervix) or to determine adverse effects for rare outcomes such as intrauterine death.

Methods/design

We propose an individual participant data meta-analysis of high quality randomized, double-blind, placebo-controlled trials of progestogen treatment in women with a twin pregnancy. The …