Biostatistics Commons^™

Correction Of Verication Bias Using Log-Linear Models For A Single Binaryscale Diagnostic Tests, Haresh Rochani, Hani M. Samawi, Robert L. Vogel, Jingjing Yin

Biostatistics Faculty Publications

In diagnostic medicine, the test that determines the true disease status without an error is referred to as the gold standard. Even when a gold standard exists, it is extremely difficult to verify each patient due to the issues of costeffectiveness and invasive nature of the procedures. In practice some of the patients with test results are not selected for verification of the disease status which results in verification bias for diagnostic tests. The ability of the diagnostic test to correctly identify the patients with and without the disease can be evaluated by measures such as sensitivity, specificity and predictive …

Effects Of Cost Sharing On Seeking Care For Serious And Minor Symptoms. Results Of A Randomized Controlled Trial, Martin Shapiro, John Ware, Cathy Sherbourne

Martin Shapiro

To estimate the effect of cost sharing on seeking care for serious and minor symptoms, we analyzed data for 3539 persons aged 17 to 61 from the Rand Health Insurance Experiment. Participants were randomly assigned to a free-care group or to insurance plans requiring them to pay part of the costs (cost-sharing group). Annual surveys were administered to determine if participants had serious and minor symptoms during the preceding month and whether they saw a physician. Serious symptoms were judged by a panel of physicians to warrant care in most instances; minor symptoms were judged neither to be severe nor …

Estimated Probability Of Becoming Alcohol Dependent: Extending A Multiparametric Approach, Olga A. Vsevolozhskaya, James C. Anthony

Biostatistics Presentations

Background: United States (US) epidemiological studies suggest that for every 5-8 who start drinking alcoholic beverages, at least one drinker will develop an alcohol dependence (AD) syndrome within the first 10 years after onset of drinking (Lopez-Quintero et al., 2011; Wagner & Anthony, 2002). Recently, we described a multiparametric functional analysis approach for new research to estimate these transition probabilities with a one-dimensional function (1D; Vsevolozhskaya & Anthony, 2015). Here, we demonstrate extension of this analysis to two-dimensional (2D) functions that combine information about number of recent drinking days and number of drinks on the typical drinking day.

Methods: Data …

Factors Impacting Transgender Patients’ Discomfort With Their Family Physicians: A Respondent-Driven Sampling Survey, Greta R. Bauer, Xuchen Zong, Ayden I. Scheim, Rebecca Hammond, Amardeep Thind

Epidemiology and Biostatistics Publications

BACKGROUND: Representing approximately 0.5% of the population, transgender (trans) persons in Canada depend on family physicians for both general and transition-related care. However, physicians receive little to no training on this patient population, and trans patients are often profoundly uncomfortable and may avoid health care. This study examined factors associated with patient discomfort discussing trans health issues with a family physician in Ontario, Canada.

METHODS: 433 trans people age 16 and over were surveyed using respondent-driven sampling for the Trans PULSE Project; 356 had a family physician. Weighted logistic regression models were fit to produce prevalence risk ratios (PRRs) via …

Monitoring For Adverse Events Post Marketing Approval Of Drugs, Karl E. Peace, Macaulay Okwuokenye

Biostatistics Faculty Publications

This brief communication provides information to those developing monitoring plans for serious adverse events (SAE’s) following regulatory approval of a new drug. In addition, we (1) illustrate how many patients would need to be treated in order to have high confidence of seeing at least 1 pre-specified SAE, (2) show that absence of proof of a SAE is not proof of absence of that SAE, and (3) identify statistical methodology that could be used for formal statistical monitoring of SAE’s.

Nested Partially-Latent, Class Models For Dependent Binary Data, Estimating Disease Etiology, Zhenke Wu, Maria Deloria-Knoll, Scott L. Zeger

Johns Hopkins University, Dept. of Biostatistics Working Papers

The Pneumonia Etiology Research for Child Health (PERCH) study seeks to use modern measurement technology to infer the causes of pneumonia for which gold-standard evidence is unavailable. The paper describes a latent variable model designed to infer from case-control data the etiology distribution for the population of cases, and for an individual case given his or her measurements. We assume each observation is drawn from a mixture model for which each component represents one cause or disease class. The model addresses a major limitation of the traditional latent class approach by taking account of residual dependence among multivariate binary outcome …

Abcc9/Sur2 In The Brain: Implications For Hippocampal Sclerosis Of Aging And A Potential Therapeutic Target, Peter T. Nelson, Gregory A. Jicha, Wang-Xia Wang, Eseosa T. Ighodaro, Sergey C. Artiushin, Colin G. Nichols, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“K _ATP ”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The K _ATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is …

Identification And Survival Outcomes Of A Cohort Of Patients With Cancer Of Unknown Primary In Ontario, Canada., Chong S Kim, Malek B Hannouf, Sisira Sarma, George B Rodrigues, Peter K Rogan, Salaheddin M Mahmud, Eric Winquist, Muriel Brackstone, Gregory S Zaric

Epidemiology and Biostatistics Publications

BACKGROUND: Cancer of unknown primary origin (CUP) is defined by the presence of pathologically identified metastatic disease without clinical or radiological evidence of a primary tumour. Our objective was to identify incident cases of CUP in Ontario, Canada, and determine the influence of histology and sites of metastases on overall survival (OS).

MATERIAL AND METHODS: We used the Ontario Cancer Registry (OCR) and the Same-Day Surgery and Discharge Abstract Database (SDS/DAD) to identify patients diagnosed with CUP in Ontario between 1 January 2000, and 31 December 2005. Patient diagnostic information, including histology and survival data, was obtained from the OCR. …

Integrated Bioinformatics, Environmental Epidemiologic And Genomic Approaches To Identify Environmental And Molecular Links Between Endometriosis And Breast Cancer, Deodutta Roy, Marisa L. Morgan, Changwon Yoo, Alok Deoraj, Sandhya Roy, Vijay Kumar Yadav, Mohannad Garoub, Hamza Assaggaf, Mayur Doke

Department of Biostatistics Faculty Publications

We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC) and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs), bisphenols (BPs), and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA) and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by …

Validation Of A New Predictive Risk Model: Measuring The Impact Of The Major Modifiable Risks Of Death For Patients And Populations, Stephen S. Lim, Emily Carnahan, Eugene C. Nelson, Catherine W. Gillespie, Ali H. Mokdad, Christopher J. L. Murray, Elliott S. Fisher

Dartmouth Scholarship

Background: Modifiable risks account for a large fraction of disease and death, but clinicians and patients lack tools to identify high risk populations or compare the possible benefit of different interventions.

Methods: We used data on the distribution of exposure to 12 major behavioral and biometric risk factors inthe US population, mortality rates by cause, and estimates of the proportional hazards of risk factor exposure from published systematic reviews to develop a risk prediction model that estimates an adult's 10 year mortality risk compared to a population with optimum risk factors. We compared predicted risk to observed mortality in 8,241 …

Functional Linear Models Extensions Uncover Pleiotropic Effects Of Chronic Pain Phenotypes, Dmitri V. Zaykin, L. Qing, G. D. Slade, R. Dubner, R. B. Fillingim, J. D. Greenspan, R. Ohrbach, W. Maixner, L. B. Diatchenko, Olga A. Vsevolozhskaya

Biostatistics Presentations

Growing scientific evidence suggests that intricate interactions of genetic risk factors with environmental exposures play a major role in the development of chronic pain conditions. In studies of relative contribution of an individual’s genetic composition to the perception of pain, the general characteristics of pain sensitivity are typically measured by a wide range of different, yet possibly etiologically related pain phenotypes. Testing each of these pain-perception traits individually is subject to problems of multiple testing and low statistical power. Furthermore, pain-related traits may share common etiology and comprise binary, categorical, and quantitative measurements. In the current study, we propose a …

Preparedness Of Hospitals In The Republic Of Ireland For An Influenza Pandemic, An Infection Control Perspective, Mary Reidy, Fiona Ryan, Dervla Hogan, Seán Lacey, Claire Buckley

Department of Mathematics Publications

When an influenza pandemic occurs most of the population is susceptible and attack rates can range as high as 40–50 %. The most important failure in pandemic planning is the lack of standards or guidelines regarding what it means to be ‘prepared’. The aim of this study was to assess the preparedness of acute hospitals in the Republic of Ireland for an influenza pandemic from an infection control perspective.

Novel Human Abcc9/Sur2 Brain-Expressed Transcripts And An Eqtl Relevant To Hippocampal Sclerosis Of Aging, Peter T. Nelson, Wang-Xia Wang, Bernard R. Wilfred, Angela Wei, James Dimayuga, Qingwei Huang, Eseosa T. Ighodaro, Sergey C. Artiushin, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

ABCC9 genetic polymorphisms are associated with increased risk for various human diseases including hippocampal sclerosis of aging. The main goals of this study were 1 > to detect the ABCC9 variants and define the specific 3′ untranslated region (3′UTR) for each variant in human brain, and 2 > to determine whether a polymorphism (rs704180) associated with risk for hippocampal sclerosis of aging pathology is also associated with variation in ABCC9 transcript expression and/or splicing. Rapid amplification of ABCC9 cDNA ends (3′RACE) provided evidence of novel 3′ UTR portions of ABCC9 in human brain. In silico and experimental studies were performed focusing on …

Extended Followup Of A Cohort Of Chromium Production Workers, Herman Jones Gibb, Peter St. John Lees, Jing Wang, Keri O'Leary

Epidemiology Faculty Publications

Background

The current study evaluates the mortality of 2,354 workers first employed at a Baltimore chromate production plant between 1950 and 1974.

Methods

The National Death Index (NDI Plus) was used to determine vital status and cause of death. Cumulative chromium (VI) exposure and nasal and skin irritation were evaluated as risk factors for lung cancer mortality.

Results

There are 91,186 person-years of observation and 217 lung cancer deaths. Cumulative chromium (VI) exposure, nasal irritation, nasal perforation, nasal ulceration, and other forms of irritation (e.g., skin irritation) were associated with lung cancer mortality.

Conclusion

Cumulative chromium (VI) exposure was a …

Sexual Networks And Hiv Risk Among Black Men Who Have Sex With Men In 6 U.S. Cities, Hong-Van Tieu, Ting-Yuan Liu, Sophia Hussen, Matthew Connor, Lei Wang, Gregory Phillips Ii, + 11 More

Epidemiology Faculty Publications

Background

Sexual networks may place U.S. Black men who have sex with men (MSM) at increased HIV risk.

Methods

Self-reported egocentric sexual network data from the prior six months were collected from 1,349 community-recruited Black MSM in HPTN 061, a multi-component HIV prevention intervention feasibility study. Sexual network composition, size, and density (extent to which members are having sex with one another) were compared by self-reported HIV serostatus and age of the men. GEE models assessed network and other factors associated with having a Black sex partner, having a partner with at least two age category difference (age difference between …

Caffeine Consumption Contributes To Skin Intrinsic Fluorescence In Type 1 Diabetes., Karen M Eny, Trevor J Orchard, Rachel Grace Miller, John Maynard, Denis M Grant, Tina Costacou, Patricia A. Cleary, Barbara H Braffett, Andrew D Paterson, Dcct/Edic Research Group

GW Biostatistics Center

Background: A variant (rs1495741) in the gene for the N-acetyltransferase 2 (NAT2) protein is associated with skin intrinsic fluorescence (SIF), a noninvasive measure of advanced glycation end products and other fluorophores in the skin. Because NAT2 is involved in caffeine metabolism, we aimed to determine whether caffeine consumption is associated with SIF and whether rs1495741 is associated with SIF independently of caffeine.

Materials and Methods: SIF was measured in 1,181 participants with type 1 diabetes from the Epidemiology of Diabetes Interventions and Complications study. Two measures of SIF were used: SIF1, using a 375-nm excitation light-emitting diode (LED), and …

Neoadjuvant Or Adjuvant Therapy For Resectable Esophageal Cancer: A Systematic Review And Meta-Analysis, Richard Malthaner, Rebecca Wong, R. Rumble, Lisa Zuraw

Richard A. Malthaner

Background: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis.

Methods: A systematic review and meta-analysis investigating the impact of neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer to inform evidence-based practice was produced.MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the American Society of Clinical Oncology and the …

Neoadjuvant Or Adjuvant Therapy For Resectable Esophageal Cancer: A Clinical Practice Guideline, Richard Malthaner, Rebecca Wong, R. Rumble, Lisa Zuraw

Richard A. Malthaner

Background: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. A clinical practice guideline was developed based on a systematic review investigating neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer. Methods: A systematic review with meta-analysis was developed and clinical recommendations were drafted. External review of the practice guideline report by practitioners in Ontario, Canada was obtained through a mailed survey, and incorporated. Final approval of the practice guideline was obtained from the Practice Guidelines Coordinating Committee. Results: The systematic review …

Neoadjuvant Or Adjuvant Therapy For Resectable Esophageal Cancer: A Systematic Review And Meta-Analysis, Richard Malthaner, Rebecca Wong, R. Rumble, Lisa Zuraw

Richard A. Malthaner

Background: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis.

Methods: A systematic review and meta-analysis investigating the impact of neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer to inform evidence-based practice was produced.MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the American Society of Clinical Oncology and the …

Neoadjuvant Or Adjuvant Therapy For Resectable Esophageal Cancer: A Clinical Practice Guideline, Richard Malthaner, Rebecca Wong, R. Rumble, Lisa Zuraw

Richard A. Malthaner

Background: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. A clinical practice guideline was developed based on a systematic review investigating neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer.

Methods: A systematic review with meta-analysis was developed and clinical recommendations were drafted. External review of the practice guideline report by practitioners in Ontario, Canada was obtained through a mailed survey, and incorporated. Final approval of the practice guideline was obtained from the Practice Guidelines Coordinating Committee.

Results: The systematic review …

Nitrate And Nitrite Ingestion And Risk Of Ovarian Cancer Among Postmenopausal Women In Iowa, Maki Inoue-Choi, Rena R. Jones, Kristin E. Anderson, Kenneth P. Cantor, James R. Cerhan, Stuart Krasner, Kimberly Robien, Peter J. Weyer, Mary H. Ward

Epidemiology Faculty Publications

Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOC), potential human carcinogens. We evaluated the association of nitrate and nitrite ingestion with postmenopausal ovarian cancer risk in the Iowa Women's Health Study. Among 28,555 postmenopausal women, we identified 315 incident epithelial ovarian cancers from 1986 to 2010. Dietary nitrate and nitrite intakes were assessed at baseline using food frequency questionnaire data. Drinking water source at home was obtained in a 1989 follow-up survey. Nitrate-nitrogen (NO₃-N) and total trihalomethane (TTHM) levels for Iowa public water utilities were linked to residences and average levels were …

Size And Power Of Tests Of Hypotheses On Survival Parameters From The Lindley Distribution With Covariates, Macaulay Okwuokenye, Karl E. Peace

Biostatistics Faculty Publications

The Lindley model is considered as an alternative model facilitating analyses of time-to-event data with covariates. Covariate information is incorporated using the Cox’s proportional hazard model with the Lindley model at the timedependent component. Simulation studies are performed to assess the size and power of tests of hypotheses on parameters arising from maximum likelihood estimators of parameters in the Lindley model. Results are contrasted with that arising from Cox’s partial maximum likelihood estimator. The Linley model is used to analyze a publicly available data set and contrasted with other models.

Joint Modeling Of Treatment Effect On Time-To-Event Endpoint And Safety Covariates In Control Clinical Trial Data Analysis, Kao-Tai Tsai, Karl E. Peace

Biostatistics Faculty Publications

It is a common practice to perform a separate analysis of efficacy and safety data from clinical trials to estimate the benefit and risk aspects of a particular treatment regimen. However, by doing so, one is likely to miss the complete picture of the treatment effect given that these data are generated from the same study subjects and therefore most likely will be correlated. Therefore, it is desirable to analyze these data jointly to obtain a more complete profile of the treatment regimen. A substantial number of statistical methodologies have been proposed in the last decade to model the time-to-event …

Estimated Probability Of Becoming A Case Of Drug Dependence In Relation To Duration Of Drug-Taking Experience: A Function Approach, Olga A. Vsevolozhskaya, James C. Anthony

Olga A. Vsevolozhskaya

Measured as elapsed time from first use to dependence syndrome onset, the estimated 'induction interval' for cocaine clearly is short relative to the cannabis interval, but little is known about risk of becoming dependent when use persists. Published estimates for this facet of drug dependence epidemiology are from life histories elicited years after first use. To improve estimation, we turn to new data from nationally representative samples of newly incident drug users identified via probability sampling and confidential computer-assisted self-interviews for the National Surveys on Drug Use and Health, 2004-2013. Standardized modules assess first and most recent use, and dependence …

A General Framework For Diagnosing Confounding Of Time-Varying And Other Joint Exposures, John W. Jackson

Harvard University Biostatistics Working Paper Series

No abstract provided.

Genetics Of Obesity In Starr County, Texas Mexican Americans, Heather M. Highland

Dissertations & Theses (Open Access)

Currently, over two-thirds of Americans are classified as over-weight or obese. Obesity increases risk for many other diseases including type 2 diabetes, heart disease, stroke, and cancer, making obesity the largest public health problem in America and most other Westernized nations. Hispanics have a higher rate of both obesity and type 2 diabetes, making them a particularly interesting population in which to study obesity. For the last 33 years, the Starr County Health Studies has collected an array of phenotypes and biological samples from residents of Starr County, along Texas-Mexico border. This study includes 825 subjects who were not known …

Association Between Nutritional Awareness And Diet Quality: Evidence From The Observation Of Cardiovascular Risk Factors In Luxembourg (Oriscav-Lux) Study, Ala'a Alkerwi, Nicolas Sauvageot, Leoné Malan, Nitin Shivappa, James R. Hébert

Faculty Publications

This study examined the association between nutritional awareness and diet quality, as indicated by energy density, dietary diversity and adequacy to achieve dietary recommendations, while considering the potentially important role of socioeconomic status (SES). Data were derived from 1351 subjects, aged 18–69 years and enrolled in the ORISCAV-LUX study. Energy density score (EDS), dietary diversity score (DDS) and Recommendation Compliance Index (RCI) were calculated based on data derived from a food frequency questionnaire. Nutritional awareness was defined as self-perception of the importance assigned to eating balanced meals, and classified as high, moderate, or of little importance. Initially, a General Linear …

Leukoaraiosis Predicts Poor 90-Day Outcome After Acute Large Cerebral Artery Occlusion, Nils Henninger, Eugene Lin, Stephen Baker, Ajay Wakhloo, Deepak Takhtani, Majaz Moonis

Nils Henninger

BACKGROUND: To date limited information regarding outcome-modifying factors in patients with acute intracranial large artery occlusion (ILAO) in the anterior circulation is available. Leukoaraiosis (LA) is a common finding among patients with ischemic stroke and has been associated with poor post-stroke outcomes but its association with ILAO remains poorly characterized. This study sought to clarify the contribution of baseline LA and other common risk factors to 90-day outcome (modified Rankin Scale, mRS) after stroke due to acute anterior circulation ILAO. METHODS: We retrospectively analyzed 1,153 consecutive patients with imaging-confirmed ischemic stroke during a 4-year period (2007-2010) at a single academic …

Genetic Associations Of Ppargc1a With Type 2 Diabetes: Differences Among Populations With African Origins, Amanpreet K. Cheema, Tan Li, Juan P. Liuzzi, Gustavo G. Zarini, Mehmet T. Dorak, Fatma G. Huffman

Department of Biostatistics Faculty Publications

The aim of this study was to assess the differences in correlation of PPARGC1A polymorphisms with type 2 diabetes (T2D) risk in adults of African origins: African Americans and Haitian Americans. The case-control study consisted of >30 years old, self-identified Haitian Americans (n = 110 cases and n = 116 controls) and African Americans (n = 124 cases and n = 122 controls) living in South Florida with and without T2D. Adjusted logistic regression indicated that both SNP rs7656250 (OR = 0.22, P = 0.005) and rs4235308 (OR = 0.42, P = 0.026) showed protective association with T2D in Haitian …

Teaching Of Biostatistics And Epidemiology In Medical Schools: How Do We Fare Compared With Developed Countries, Vijay Tiwari, Kuldeep Kumar, Sherin Raj

Kuldeep Kumar

Background Biostatistics is taught in almost all medical schools at the undergraduate and the postgraduate levels as a core course and is a prerequisite to epidemiology, public health and evidence-based medicine. However, it has to be taught in a different way in medical schools as compared with how it is taught to the students studying MSc (Biostatistics) or in the Statistics Department in universities. Objectives (1) To review the experience of teaching biostatistics in medical schools in India and compares the same with abroad (2) How best the curriculum can be designed as per the need of the medical students …