Biostatistics Commons^™

Correlation Of Positron Emission Tomography/Computed Tomography Scan With Smoking, Tumor Size, Stage And Differentiation In Head And Neck Cancer Patients, Jordan L. Pleitz, Partha Sinha, Emily V. Dressler, Rony K. Aouad

Otolaryngology--Head & Neck Surgery Faculty Publications

The goal of this study was to identify associations between positron emission tomography/computed tomography (PET/CT) maximum standardized uptake value (SUVmax) in patients presenting with head and neck squamous cell carcinoma (SCC) with tumor site, size, histologic differentiation, smoking, and diabetes. Charts of patients with oropharyngeal and laryngeal SCC who underwent ¹⁸F-fluorodeoxyglucose PET/CT scans were reviewed between May 2007 and August 2013. Statistical analyses included modeling log-transformed SUVmax values by tumor site, size, histologic differentiation, smoking status, and diabetes using unadjusted linear regressions. Differences were considered statistically significant for P< 0.05. A total of 111 patients (54 with oropharynx and 57 with larynx cancers) were included, 83 men and 28 women with an average age of 57.5 years old. There was a significantly higher pack-year smoking history (P = 0.005) in the larynx cancer group. While tumor …

Quantifying The Totality Of Treatment Effect With Multiple Event-Time Observations In The Presence Of A Terminal Event From A Comparative Clinical Study, Brian Claggett, Lu Tian, Haoda Fu, Scott D. Solomon, L. J. Wei

Harvard University Biostatistics Working Paper Series

To evaluate the totality of one treatment's benefit/risk profile relative to an alternative treatment via a longitudinal comparative clinical study, the timing and occurrence of multiple clinical events are typically collected during the patient's followup. These multiple observations reflect the patient's disease progression/burden over time. The standard practice is to create a composite endpoint from the multiple outcomes, the timing of the occurrence of the first clinical event, to evaluate the treatment via the standard survival analysis techniques. By ignoring all events after the composite outcome, this type of assessment may not be ideal. Various parametric or semi-parametric procedures have …

Tuning Parameter Selection In Cox Proportional Hazards Model With A Diverging Number Of Parameters, Andy Ni, Jianwen Cai

Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series

Regularized variable selection is a powerful tool for identifying the true regression model from a large number of candidates by applying penalties to the objective functions. The penalty functions typically involve a tuning parameter that control the complexity of the selected model. The ability of the regularized variable selection methods to identify the true model critically depends on the correct choice of the tuning parameter. In this study we develop a consistent tuning parameter selection method for regularized Cox's proportional hazards model with a diverging number of parameters. The tuning parameter is selected by minimizing the generalized information criterion. We …

Variance Prior Specification For A Basket Trial Design Using Bayesian Hierarchical Modeling, Kristen Cunanan, Alexia Iasonos, Ronglai Shen, Mithat Gonen

Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series

Background: In the era of targeted therapies, clinical trials in oncology are rapidly evolving, wherein patients from multiple diseases are now enrolled and treated according to their genomic mutation(s). In such trials, known as basket trials, the different disease cohorts form the different baskets for inference. Several approaches have been proposed in the literature to efficiently use information from all baskets while simultaneously screening to find individual baskets where the drug works. Most proposed methods are developed in a Bayesian paradigm that requires specifying a prior distribution for a variance parameter, which controls the degree to which information is shared …

Optimized Variable Selection Via Repeated Data Splitting, Marinela Capanu, Colin B. Begg, Mithat Gonen

Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series

We introduce a new variable selection procedure that repeatedly splits the data into two sets, one for estimation and one for validation, to obtain an empirically optimized threshold which is then used to screen for variables to include in the final model. Simulation results show that the proposed variable selection technique enjoys superior performance compared to candidate methods, being amongst those with the lowest inclusion of noisy predictors while having the highest power to detect the correct model and being unaffected by correlations among the predictors. We illustrate the methods by applying them to a cohort of patients undergoing hepatectomy …

Mediation Analysis For Censored Survival Data Under An Accelerated Failure Time Model, Isabel Fulcher, Eric J. Tchetgen Tchetgen, Paige Williams

Harvard University Biostatistics Working Paper Series

Recent advances in causal mediation analysis have formalized conditions for estimating direct and indirect effects in various contexts. These approaches have been extended to a number of models for survival outcomes including accelerated failure time (AFT) models which are widely used in a broad range of health applications given their intuitive interpretation. In this setting, it has been suggested that under standard assumptions, the “difference” and “product” methods produce equivalent estimates of the indirect effect of exposure on the survival outcome. We formally show that these two methods may produce substantially different estimates in the presence of censoring or truncation, …

Studying The Optimal Scheduling For Controlling Prostate Cancer Under Intermittent Androgen Suppression, Sunil K. Dhar, Hans R. Chaudhry, Bruce G. Bukiet, Zhiming Ji, Nan Gao, Thomas W. Findley

Harvard University Biostatistics Working Paper Series

This retrospective study shows that the majority of patients’ correlations between PSA and Testosterone during the on-treatment period is at least 0.90. Model-based duration calculations to control PSA levels during off-treatment are provided. There are two pairs of models. In one pair, the Generalized Linear Model and Mixed Model are both used to analyze the variability of PSA at the individual patient level by using the variable “Patient ID” as a repeated measure. In the second pair, Patient ID is not used as a repeated measure but additional baseline variables are included to analyze the variability of PSA.

Gender Differences In Hiv Care Among Criminal Justice-Involved Persons: Baseline Data From The Care+ Corrections Study., Curt Beckwith, Breana Uhrig Castonguay, Claudia Trezza, Lauri Bazerman, Rudy Patrick, Alice Cates, Halli Olsen, Ann Kurth, Tao Liu, James Peterson, Irene Kuo

Epidemiology Faculty Publications

BACKGROUND: HIV-infected individuals recently released from incarceration have suboptimal linkage and engagement in community HIV care. We conducted a study to evaluate an information and communication technology intervention to increase linkage to community care among HIV-infected persons recently involved in the criminal justice (CJ) system. Baseline characteristics including risk behaviors and HIV care indicators are reported and stratified by gender.

METHODS: We recruited HIV-infected individuals in the District of Columbia jail and persons with a recent history of incarceration through community and street outreach. Participants completed a baseline computer-assisted personal interview regarding HIV care and antiretroviral treatment (ART) adherence, substance …

Use Of National Standards To Monitor Hiv Care And Treatment In A High Prevalence City-Washington, Dc., Amanda D Castel, Arpi Terzian, Rachel Hart, Nabil Rayeed, Mariah M Kalmin, Heather Young, Alan E Greenberg

Epidemiology Faculty Publications

We sought to benchmark the quality of HIV care being received by persons living with HIV in care in Washington, DC and identify individual-level and structural-level differences. Data from the DC Cohort, an observational HIV cohort of persons receiving outpatient care in DC, were used to estimate the Institute of Medicine (IOM) and Department of Health and Human Services (HHS) quality of care measures. Differences in care by demographics and clinic type were assessed using χ2 tests and multivariable regression models. Among 8,047 participants, by HHS standards, 69% of participants were retained in care (RIC), 95% were prescribed antiretroviral therapy …

Conventional Early Infant Diagnosis In Lesotho From Specimen Collection To Results Usage To Manage Patients: Where Are The Bottlenecks?, Appolinaire Tiam, Michelle M Gill, Heather J Hoffman, Anthony Isavwa, Mafusi Mokone, Matokelo Foso, Jeffrey T Safrit, Lynne M Mofenson, Thorkild Tylleskär, Laura Guay

Epidemiology Faculty Publications

INTRODUCTION: Early infant diagnosis is an important step in identifying children infected with HIV during the perinatal period or in utero. Multiple factors contribute to delayed antiretroviral treatment initiation for HIV-infected children, including delays in the early infant HIV diagnosis cascade.

METHODS: We conducted a retrospective study to evaluate early infant diagnosis turnaround times in Lesotho. Trained staff reviewed records of HIV-exposed infants (aged-6-8 weeks) who received an HIV test during 2011. Study sites were drawn from Highlands, Foothills and Lowlands regions of Lesotho. Central laboratory database data were linked to facility and laboratory register information. Turnaround time geometric means …

Conventional Early Infant Diagnosis In Lesotho From Specimen Collection To Results Usage To Manage Patients: Where Are The Bottlenecks?, Appolinaire Tiam, Michelle M Gill, Heather J Hoffman, Anthony Isavwa, Mafusi Mokone, Matokelo Foso, Jeffrey T Safrit, Lynne M Mofenson, Thorkild Tylleskär, Laura Guay

Epidemiology Faculty Publications

Introduction

Early infant diagnosis is an important step in identifying children infected with HIV during the perinatal period or in utero. Multiple factors contribute to delayed antiretroviral treatment initiation for HIV-infected children, including delays in the early infant HIV diagnosis cascade.

Methods

We conducted a retrospective study to evaluate early infant diagnosis turnaround times in Lesotho. Trained staff reviewed records of HIV-exposed infants (aged-6-8 weeks) who received an HIV test during 2011. Study sites were drawn from Highlands, Foothills and Lowlands regions of Lesotho. Central laboratory database data were linked to facility and laboratory register information. Turnaround time geometric means …

Assessing Very Early Infant Diagnosis Turnaround Times: Findings From A Birth Testing Pilot In Lesotho, Michelle Gill, Heather J. Hoffman, Majoalane Mokone, Vincent Tukei, Matsepeli Nchephe, +Several Additional Authors

Epidemiology Faculty Publications

Very early infant diagnosis (VEID) (testing within two weeks of life), combined with rapid treatment initiation, could reduce early infant mortality. Our study evaluated turnaround time (TAT) to receipt of infants’ HIV test results and ART initiation if HIV-infected, with and without birth testing availability. Data from facility records and national databases were collected for 12 facilities offering VEID, as part of an observational prospective cohort study, and 10 noncohort facilities. HIV-exposed infants born in January–June 2016 and any cohort infant diagnosed as HIV-infected at birth or six weeks were included. The median TAT from blood draw to caregiver result …

Risk Of Gastrointestinal Bleeding Among Dabigatran Users – A Self Controlled Case Series Analysis, Wenze Tang, Hsien-Yen Chang, Meijia Zhou, Sonal Singh

Epidemiology Faculty Publications

This article aims to evaluate the real world risk of gastrointestinal bleeding among users naïve to dabigatran. We adopted a self-controlled case series design. We sampled 1215 eligible adult participants who were continuous insured users between July 1, 2010 and March 31, 2012 with use of dabigatran and at least one gastrointestinal bleeding episode. We used a conditional Poisson regression to estimate incidence rate ratios. The population consisted of 64.69% of male and 60.25% patients equal to or greater than age 65 at start of observation. After adjustment for time-variant confounders, the incidence rate of gastrointestinal bleeding was similar during …

Post-Diagnosis Body Mass Index And Mortality Among Women Diagnosed With Endometrial Cancer: Results From The Women's Health Initiative., Hannah Arem, Ruth M Pfeiffer, Steven C Moore, Melinda L Irwin, Michael J Lamonte, Gloria E Sarto, Rami Nassir, Juhua Luo, Rowan T Chlebowski, Louise A Brinton, Charles E Matthews

Epidemiology Faculty Publications

Higher body mass index (BMI) measured before endometrial cancer diagnosis has been associated with greater risk of developing endometrial cancer and higher mortality, but the association between BMI measured after diagnosis and mortality risk is unclear. We identified 467 women (91 deaths) in the Women's Health Initiative (WHI) with information on BMI measured after diagnosis and used Cox proportional hazards regression to generate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality. Comparing BMI 35+ with/m2, we observed no association with all-cause mortality (HR = 1.02, 95% CI 0.55-1.91). Our study does not support the hypothesis that higher …

Statin Use And Risk Of Developing Diabetes: Results From The Diabetes Prevention Program, Diabetes Prevention Program(Dpp) Research Group, Marinella G. Temprosa

GW Biostatistics Center

Objective Several clinical trials of cardiovascular disease prevention with statins have reported increased risk of type 2 diabetes (T2DM) with statin therapy. However, participants in these studies were at relatively low risk for diabetes. Further, diabetes was often based on self-report and was not the primary outcome. It is unknown whether statins similarly modify diabetes risk in higher risk populations.

Research design and methods During the Diabetes Prevention Program Outcomes Study (n=3234), the long-term follow-up to a randomized clinical trial of interventions to prevent T2DM, incident diabetes was assessed by annual 75 g oral glucose tolerance testing and semiannual fasting …

Anti-Müllerian Hormone And Its Relationships With Subclinical Cardiovascular Disease And Renal Disease In A Longitudinal Cohort Study Of Women With Type 1 Diabetes, Catherine Kim, Yuanyuan Pan, Barbara Braffett, Valerie Arends, Michael Steffes, Hunter Wessells, Aruna V. Sarma

GW Biostatistics Center

Background

Reproductive age may be a risk factor for vascular disease. Anti-Müllerian hormone (AMH) is produced by viable ovarian follicles and reflects reproductive age. We examined whether AMH concentrations were associated with markers of subclinical cardiovascular disease (CVD) and kidney disease among women with type 1 diabetes.

Methods

We performed a cross-sectional analysis of the Epidemiology of Diabetes Interventions and Complications Study. Participants included women with type 1 diabetes and ≥1 AMH measurement (n = 390). In multivariable regression models which adjusted for repeated measures, we examined the associations between AMH with CVD risk factors, estimated glomerular filtration rate, …

Biomarkers Of Tubulointerstitial Damage And Function In Type 1 Diabetes, Ian De Boer, Xiaoyu Gao, Ionut Bebu, Andrew Hoofnagle, John Lachin, Diabetes Control And Complications Trial/Epidemiology Of Diabetes Interventions And Complications (Dcct/Edic) Research Group.

Epidemiology Faculty Publications

Objective To evaluate biomarkers of renal tubulointerstitial damage and function in type 1 diabetes with and without diabetic kidney disease.

Research design and methods Cross-sectional case-control study of Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study participants. Cases (N=43) had incident persistent estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 with urinary albumin excretion >300 mg/24 hour. Controls (N=43) had persistent eGFR >90 mL/min/1.73 m2 and urinary albumin excretion <30 mg/24 hour. Urinary and plasma biomarkers reflecting tubular injury, inflammation, fibrosis, secretion, and synthetic function were measured from stored specimens collected at the first study visit with reduced eGFR (for case participants) or the corresponding study year (for control participants).

Results Mean (SD) age was 51 (9) and 50 (8) years for case and control participants, and mean (SD) duration of diabetes was 30 (6) and 30 (5) years, respectively. Mean (SD) eGFR was 39 …

Detecting Discordance Enrichment Among A Series Of Two-Sample Genome-Wide Expression Data Sets, Yinglei Lai, Fanni Zhang, Tapan Nayak, Reza Modarres, Norman H. Lee, Timothy A. Mccaffrey

Epidemiology Faculty Publications

Background

With the current microarray and RNA-seq technologies, two-sample genome-wide expression data have been widely collected in biological and medical studies. The related differential expression analysis and gene set enrichment analysis have been frequently conducted. Integrative analysis can be conducted when multiple data sets are available. In practice, discordant molecular behaviors among a series of data sets can be of biological and clinical interest.

Methods

In this study, a statistical method is proposed for detecting discordance gene set enrichment. Our method is based on a two-level multivariate normal mixture model. It is statistically efficient with linearly increased parameter space when …

Willingness Of Community-Recruited Men Who Have Sex With Men In Washington, Dc To Use Long-Acting Injectable Hiv Pre-Exposure Prophylaxis., Matthew E Levy, Rudy Patrick, Jonjelyn Gamble, Anthony Rawls, Jenevieve Opoku, Manya Magnus, Michael Kharfen, Alan E Greenberg, Irene Kuo

Epidemiology Faculty Publications

Objectives

Clinical trials are currently investigating the safety and efficacy of long-acting injectable (LAI) agents as HIV pre-exposure prophylaxis (PrEP). Using National HIV Behavioral Surveillance data, we assessed the self-reported willingness of men who have sex with men (MSM) to use LAI PrEP and their preference for LAI versus daily oral PrEP.

Methods

In 2014, venue-based sampling was used to recruit MSM aged ≥18 years in Washington, DC. Participants completed an interviewer-administered survey followed by voluntary HIV testing. This analysis included MSM who self-reported negative/unknown HIV status at study entry. Correlates of being “very likely” to use LAI PrEP and …

Examining The Activities, Effectiveness, And Contribution Of Local Health Departments Using A National Longitudinal Survey Of Public Health Systems, Lava R. Timsina

Theses and Dissertations--Epidemiology and Biostatistics

Health services research and public health services and systems research in the past have contributed to a strong foundation of evidence-based progress in organizing, financing, and delivering medical care and public health strategies across the United States. The purpose of this dissertation was to examine disparities in public health systems and in the delivery of population health services in communities served by these systems using nationally representative data from the National Longitudinal Survey of Local Public Health Systems (1998, 2006, 2012, and 2014).

Data from the 1998 cohort of 497 local health jurisdictions serving at least 100,000 residents, and from …