Biostatistics Commons^™

Tests For Gene-Environment Interactions And Joint Effects With Exposure Misclassification, Philip S. Boonstra, Bhramar Mukherjee, Stephen B. Gruber, Jaeil Ahn, Stephanie L. Schmit, Nilanjan Chatterjee

The University of Michigan Department of Biostatistics Working Paper Series

The number of methods for genome-wide testing of gene-environment interactions (GEI) continues to increase with the hope of discovering new genetic risk factors and obtaining insight into the disease-gene-environment relationship. The relative performance of these methods based on family-wise type 1 error rate and power depends on underlying disease-gene-environment associations, estimates of which may be biased in the presence of exposure misclassification. This simulation study expands on a previously published simulation study of methods for detecting GEI by evaluating the impact of exposure misclassification. We consider seven single step and modular screening methods for identifying GEI at a genome-wide level …

A History Of Undergraduate Education For Public Health: From Behind The Scenes To Center Stage., Richard Kenneth Riegelman, Susan Albertine, Randy Wykoff

GW Biostatistics Center

No abstract provided.

Scaling Down To Scale Up: A Health Economic Analysis Of Integrating Point-Of-Care Syphilis Testing Into Antenatal Care In Zambia During Pilot And National Rollout Implementation., Katharine D. Shelley, Éimhín M. Ansbro, Alexander Tshaka Ncube, Sedona Sweeney, Colette Fleischer, Grace Tembo Mumba, Michelle M. Gill, Susan Strasser, Rosanna W. Peeling, Fern Terris-Prestholt

GW Biostatistics Center

Maternal syphilis results in an estimated 500,000 stillbirths and neonatal deaths annually in Sub-Saharan Africa. Despite the existence of national guidelines for antenatal syphilis screening, syphilis testing is often limited by inadequate laboratory and staff services. Recent availability of inexpensive rapid point-of-care syphilis tests (RST) can improve access to antenatal syphilis screening. A 2010 pilot in Zambia explored the feasibility of integrating RST within prevention of mother-to-child-transmission of HIV services. Following successful demonstration, the Zambian Ministry of Health adopted RSTs into national policy in 2011. Cost data from the pilot and 2012 preliminary national rollout were extracted from project records, …

Treatment-Induced Changes In Plasma Adiponectin Do Not Reduce Urinary Albumin Excretion In The Diabetes Prevention Program Cohort., Kieren J. Mather, Qing Pan, William C. Knowler, Tohru Funahashi, George A. Bray, Et Al.

GW Biostatistics Center

BACKGROUND AND OBJECTIVES: Molecular data suggests that adiponectin may directly regulate urinary albumin excretion. In the Diabetes Prevention Program (DPP) we measured adiponectin and albuminuria before and after intervention, and we previously reported increases in adiponectin with interventions. Here we have used the DPP dataset to test the hypothesis that treatment-related increases in adiponectin may reduce albuminuria in obesity.

DESIGN, SETTING, PARTICIPANTS AND METHODS: We evaluated cross-sectional correlations between plasma adiponectin and urinary albumin excretion at baseline, and the relationship of treatment-related changes in adiponectin and albuminuria. Baseline and follow-up urine albumin to creatinine ratios (ACR (albumin to creatinine ratio)) …

The Cost-Effectiveness Of Diabetes Prevention: Results From The Diabetes Prevention Program And The Diabetes Prevention Program Outcomes Study, William H. Herman

GW Biostatistics Center

Background

The Diabetes Prevention Program (DPP) was a randomized, controlled clinical trial. It demonstrated that among high-risk individuals with impaired glucose tolerance, diabetes incidence was reduced by 58 % with lifestyle intervention and 31 % with metformin compared to placebo. During the Diabetes Prevention Program Outcomes Study (DPPOS), all DPP participants were unmasked to their treatment assignments, the original lifestyle intervention group was offered additional lifestyle support, the metformin group continued metformin, and all three groups were offered a group-implemented lifestyle intervention. Over the 10 years of combined DPP/DPPOS follow-up, diabetes incidence was reduced by 34 % in the lifestyle …

Skin Collagen Advanced Glycation Endproducts (Ages) And The Long-Term Progression Of Sub-Clinical Cardiovascular Disease In Type 1 Diabetes, Vincent M. Monnier, Wanjie Sun, Xiaoyu Gao, David R. Sell, Patricia Cleary, John M. Lachin, Saul Genuth, The Dcct/Edic Research Group

GW Biostatistics Center

BACKGROUND:

We recently reported strong associations between eight skin collagen AGEs and two solubility markers from skin biopsies obtained at DCCT study closeout and the long-term progression of microvascular disease in EDIC, despite adjustment for mean glycemia. Herein we investigated the hypothesis that some of these AGEs (fluorescence to be reported elsewhere) correlate with long-term subclinical cardiovascular disease (CVD) measurements, i.e. coronary artery calcium score (CAC) at EDIC year 7-9 (n = 187), change of carotid intima-media thickness (IMT) from EDIC year 1 to year 6 and 12 (n = 127), and cardiac MRI outcomes at EDIC year 15-16 (n …

Quality Control Measures Over 30 Years In A Multicenter Clinical Study: Results From The Diabetes Control And Complications Trial / Epidemiology Of Diabetes Interventions And Complications (Dcct/Edic) Study., Gayle M Lorenzi, Barbara H Braffett, Valerie L Arends, Ronald P Danis, Lisa Diminick, Kandace A Klumpp, Anthony D Morrison, Elsayed Z Soliman, Michael W Steffes, Patricia A Cleary

GW Biostatistics Center

No abstract provided.

The Cost-Effectiveness Of Diabetes Prevention: Results From The Diabetes Prevention Program And The Diabetes Prevention Program Outcomes Study, William Herman

GW Biostatistics Center

Background

The Diabetes Prevention Program (DPP) was a randomized, controlled clinical trial. It demonstrated that among high-risk individuals with impaired glucose tolerance, diabetes incidence was reduced by 58 % with lifestyle intervention and 31 % with metformin compared to placebo. During the Diabetes Prevention Program Outcomes Study (DPPOS), all DPP participants were unmasked to their treatment assignments, the original lifestyle intervention group was offered additional lifestyle support, the metformin group continued metformin, and all three groups were offered a group-implemented lifestyle intervention. Over the 10 years of combined DPP/DPPOS follow-up, diabetes incidence was reduced by 34 % in the lifestyle …

Pregnant And Postpartum Women’S Experiences And Perspectives On The Acceptability And Feasibility Of Copackaged Medicine For Antenatal Care And Pmtct In Lesotho, Michelle M. Gill, Heather J. Hoffman, Appolinaire Tiam, Florence M. Mohai, Mokone Majoalane, Anthony Isavwa, Laura Guay, +4 Additional Authors

Epidemiology Faculty Publications

Objective. To improve PMTCT and antenatal care-related service delivery, a pack with centrally prepackaged medicine was rolled out to all pregnant women in Lesotho in 2011. This study assessed acceptability and feasibility of this copackaging mechanism for drug delivery among pregnant and postpartum women.

Methods. Acceptability and feasibility were assessed in a mixed method, cross-sectional study through structured interviews (SI) and semistructured interviews (SSI) conducted in 2012 and 2013.

Results. 290 HIV-negative women and 437 HIV-positive women (n=727) participated. Nearly all SI participants found prepackaged medicines acceptable, though modifications such as size reduction of the pack were …

Clinical Significance Of Left Atrial Anatomic Abnormalities Identified By Cardiac Computed Tomography, Ara V. Vehian, Brian G. Choi, Satinder Rekhi, Heather A. Young, Raman S. Dusaj, Robert K. Zeman

Epidemiology Faculty Publications

Purpose: The clinical significance of newly identified left atrial anatomic abnormalities (LAAA)— accessory appendages, diverticula, septal pouches—by multidetector CT (MDCT) remains unclear. Similar anatomical outpouchings, i.e., the left atrial appendage, have been associated with cardioembolisms and arrhythmia. To test the hypothesis that LAAA are also associated with increased risk of these events, we performed a retrospective analysis to examine the association of LAAA in patients undergoing CT with embolic events and arrhythmia.

Methods: 242 patients (mean age 56 SD 12 years, 41% female) were selected who had CT coronary angiography performed with 64-row MDCT between 2007 and 2012 if complete …

Parity And Diabetes Risk Among Hispanic Women From Colombia: Cross-Sectional Evidence, Pablo Cure, Heather J. Hoffman, Carlos Cure-Cure

Epidemiology Faculty Publications

Objective

The association between parity and type 2 diabetes has been studied in developed countries and in Singapore and Chinese women but not in Hispanics. Herein we evaluated the association between parity (number of live births) with diabetes in a group of Hispanic postmenopausal women from Colombia.

Research design and methods

Herein we evaluated the association between parity and diabetes in a population of 1,795 women from Colombia. Women were divided in birth categories (0 [referent], 1 or 2, 3–5, 6 or > births). Medical history of diabetes and anthropometric characteristics were recorded. Logistic regressions were performed in order to find …

Implementation Of Point-Of-Care Diagnostics Leads To Variable Uptake Of Syphilis, Anemia And Cd4+ T-Cell Count Testing In Rural Maternal And Child Health Clinics., Caroline De Schacht, Carlota Lucas, Nádia Sitoe, Rhoderick Machekano, Patrina Chongo, Laura Guay, Et Al.

Epidemiology Faculty Publications

INTRODUCTION: Anemia, syphilis and HIV are high burden diseases among pregnant women in sub-Saharan Africa. A quasi-experimental study was conducted in four health facilities in Southern Mozambique to evaluate the effect of point-of-care technologies for hemoglobin quantification, syphilis testing and CD4+ T-cell enumeration performed within maternal and child health services on testing and treatment coverage, and assessing acceptability by health workers.

METHODS: Demographic and testing data on women attending first antenatal care services were extracted from existing records, before (2011; n = 865) and after (2012; n = 808) introduction of point-of-care testing. Study outcomes per health facility were compared …

A Systematic Review And Meta-Regression Analysis Of Lung Cancer Risk And Inorganic Arsenic In Drinking Water., Steven H. Lamm, Hamid Ferdosi, Elisabeth K. Dissen, Ji Li, Jaeil Ahn

Epidemiology Faculty Publications

High levels (> 200 µg/L) of inorganic arsenic in drinking water are known to be a cause of human lung cancer, but the evidence at lower levels is uncertain. We have sought the epidemiological studies that have examined the dose-response relationship between arsenic levels in drinking water and the risk of lung cancer over a range that includes both high and low levels of arsenic. Regression analysis, based on six studies identified from an electronic search, examined the relationship between the log of the relative risk and the log of the arsenic exposure over a range of 1-1000 µg/L. The …

Reassessment Of Risk Genotypes (Grn, Tmem106b, And Abcc9 Variants) Associated With Hippocampal Sclerosis Of Aging Pathology, Peter T. Nelson, Wang-Xia Wang, Amanda B. Partch, Sarah E. Monsell, Otto Valladares, Sally R. Ellingson, Bernard R. Wilfred, Adam C. Naj, Li-San Wang, Walter A. Kukull, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

Hippocampal sclerosis of aging (HS-Aging) is a common high-morbidity neurodegenerative condition in elderly persons. To understand the risk factors for HS-Aging, we analyzed data from the Alzheimer’s Disease Genetics Consortium and correlated the data with clinical and pathologic information from the National Alzheimer’s Coordinating Center database. Overall, 268 research volunteers with HS-Aging and 2,957 controls were included; detailed neuropathologic data were available for all. The study focused on single-nucleotide polymorphisms previously associated with HS-Aging risk: rs5848 ( GRN ), rs1990622 ( TMEM106B ), and rs704180 ( ABCC9 ). Analyses of a subsample that was not previously evaluated (51 HS-Aging cases …

Developing A Weibull Model Extension To Estimate Cancer Latency Times, Diana L. Nadler

Legacy Theses & Dissertations (2009 - 2024)

More than one-third of all Americans will be diagnosed with cancer sometime in their lives. Though their illness may be invisible now, it presents a great, and largely unexamined, opportunity to find and treat their cancers early. Early detection represents one of the most promising approaches to reduce the growing cancer burden by identifying cancer while it is localized and curable, preventing not only mortality, but also reducing morbidity and costs.

Two Step Parsimonious Variable Selection For Right Censored Continuous Survival Time Models, Anju Menon

Legacy Theses & Dissertations (2009 - 2024)

Variable selection is fundamental in any kind of statistical modeling. There has been ex- tensive research by different authors on methods of variable selection from linear regression models to more complex non-linear applications. Modeling survival data especially poses challenges because of a more complicated data structure as the time variable T is usually subject to censoring. This thesis presents a two step objective approach to choose between several candidate models based on the the ability of the model to predict survival times using loss functions. Once potentially important variables are selected using a screening method called Iterative Sure Independence Screening(ISIS) …

Diffuse Optical Measurements Of Head And Neck Tumor Hemodynamics For Early Prediction Of Chemo-Radiation Therapy Outcomes, Lixin Dong

Theses and Dissertations--Biomedical Engineering

Chemo-radiation therapy is a principal modality for the treatment of head and neck cancers, and its efficacy depends on the interaction of tumor oxygen with free radicals. In this study, we adopted a novel hybrid diffuse optical instrument combining a commercial frequency-domain tissue oximeter (Imagent) and a custom-made diffuse correlation spectroscopy (DCS) flowmeter, which allowed for simultaneous measurements of tumor blood flow and blood oxygenation. Using this hybrid instrument we continually measured tumor hemodynamic responses to chemo-radiation therapy over the treatment period of 7 weeks. We also explored monitoring dynamic tumor hemodynamic changes during radiation delivery. Blood flow data analysis …

Multi-State Models For Interval Censored Data With Competing Risk, Shaoceng Wei

Theses and Dissertations--Statistics

Multi-state models are often used to evaluate the effect of death as a competing event to the development of dementia in a longitudinal study of the cognitive status of elderly subjects. In this dissertation, both multi-state Markov model and semi-Markov model are used to characterize the flow of subjects from intact cognition to dementia with mild cognitive impairment and global impairment as intervening transient, cognitive states and death as a competing risk.

Firstly, a multi-state Markov model with three transient states: intact cognition, mild cognitive impairment (M.C.I.) and global impairment (G.I.) and one absorbing state: dementia is used to model …

Developments In Nonparametric Regression Methods With Application To Raman Spectroscopy Analysis, Jing Guo

Theses and Dissertations--Epidemiology and Biostatistics

Raman spectroscopy has been successfully employed in the classification of breast pathologies involving basis spectra for chemical constituents of breast tissue and resulted in high sensitivity (94%) and specificity (96%) (Haka et al, 2005). Motivated by recent developments in nonparametric regression, in this work, we adapt stacking, boosting, and dynamic ensemble learning into a nonparametric regression framework with application to Raman spectroscopy analysis for breast cancer diagnosis. In Chapter 2, we apply compound estimation (Charnigo and Srinivasan, 2011) in Raman spectra analysis to classify normal, benign, and malignant breast tissue. We explore both the spectra profiles and their derivatives to …

Nonlinear Hierarchical Models For Longitudinal Experimental Infection Studies, Michael David Singleton

Theses and Dissertations--Epidemiology and Biostatistics

Experimental infection (EI) studies, involving the intentional inoculation of animal or human subjects with an infectious agent under controlled conditions, have a long history in infectious disease research. Longitudinal infection response data often arise in EI studies designed to demonstrate vaccine efficacy, explore disease etiology, pathogenesis and transmission, or understand the host immune response to infection. Viral loads, antibody titers, symptom scores and body temperature are a few of the outcome variables commonly studied. Longitudinal EI data are inherently nonlinear, often with single-peaked response trajectories with a common pre- and post-infection baseline. Such data are frequently analyzed with statistical methods …