Biostatistics Commons^™

Dichotomous Scoring Of Tdp-43 Proteinopathy From Specific Brain Regions In 27 Academic Research Centers: Associations With Alzheimer's Disease And Cerebrovascular Disease Pathologies, Yuriko Katsumata, David W. Fardo, Walter A. Kukull, Peter T. Nelson

Biostatistics Faculty Publications

TAR-DNA binding protein 43 (TDP-43) proteinopathy is a common brain pathology in elderly persons, but much remains to be learned about this high-morbidity condition. Published stage-based systems for operationalizing disease severity rely on the involvement (presence/absence) of pathology in specific anatomic regions. To examine the comorbidities associated with TDP-43 pathology in aged individuals, we studied data from the National Alzheimer’s Coordinating Center (NACC) Neuropathology Data Set. Data were analyzed from 929 included subjects with available TDP-43 pathology information, sourced from 27 different American Alzheimer’s Disease Centers (ADCs). Cases with relatively unusual diseases including autopsy-proven frontotemporal lobar degeneration (FTLD-TDP or FTLD-tau) …

Large-Scale Genome-Wide Meta-Analysis Of Polycystic Ovary Syndrome Suggests Shared Genetic Architecture For Different Diagnosis Criteria, Felix Day, Tugce Karaderi, Michelle R. Jones, Cindy Meun, Chunyan He, Alex Drong, Peter Kraft, Nan Lin, Hongyan Huang, Linda Broer, Reedik Magi, Richa Saxena, Triin Laisk, Margrit Urbanek, M. Geoffrey Hayes, Gudmar Thorleifsson, Juan Fernandez-Tajes, Anubha Mahajan, Benjamin H. Mullin, Bronwyn G. A. Stuckey, Timothy D. Spector, Scott G. Wilson, Mark O. Goodarzi, Lea Davis, Barbara Obermayer-Pietsch, André G. Uitterlinden, Verneri Anttila, Benjamin M. Neale, Marjo-Riitta Jarvelin, Bart Fauser

Internal Medicine Faculty Publications

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related …

Serum Nutrient Levels And Aging Effects On Periodontitis, Jeffrey L Ebersole, Joshua Lambert, Heather Bush, Pinar Emecen Huja, Arpita Basu

Biostatistics Faculty Publications

Periodontal disease damages tissues as a result of dysregulated host responses against the chronic bacterial biofilm insult and approximately 50% of US adults > 30 years old exhibit periodontitis. The association of five blood nutrients and periodontitis were evaluated due to our previous findings regarding a potential protective effect for these nutrients in periodontal disease derived from the US population sampled as part of the National Health and Nutrition Examination Survey (1999–2004). Data from over 15,000 subjects was analyzed for blood levels of cis-β-carotene, β-cryptoxanthin, folate, vitamin D, and vitamin E, linked with analysis of the presence and severity of periodontitis. …

A Logitudinal Feature Selection Method Identifies Relevant Genes To Distinguish Complicated Injury And Uncomplicated Injury Over Time, Suyan Tian, Chi Wang, Howard H. Chang

Biostatistics Faculty Publications

Background: Feature selection and gene set analysis are of increasing interest in the field of bioinformatics. While these two approaches have been developed for different purposes, we describe how some gene set analysis methods can be utilized to conduct feature selection.

Methods: We adopted a gene set analysis method, the significance analysis of microarray gene set reduction (SAMGSR) algorithm, to carry out feature selection for longitudinal gene expression data.

Results: Using a real-world application and simulated data, it is demonstrated that the proposed SAMGSR extension outperforms other relevant methods. In this study, we illustrate that a gene’s expression profiles over …

Blood Transfusions In Preterm Infants: Changes On Perfusion Index And Intermittent Hypoxemia, Katrina T. Ibonia, Henrietta S. Bada, Philip M. Westgate, Enrique Gomez Pomar, Prasad Bhandary, Abhijit R. Patwardhan, Elie G. Abu Jawdeh

Pediatrics Faculty Publications

BACKGROUND

Red blood cell (RBC) transfusion decreases intermittent hypoxemia (IH) events beyond the first week of life. This benefit may be related to improved perfusion to the respiratory control network. Perfusion index (PI) is a perfusion measure provided by the pulse oximeter. We hypothesized that the benefit in IH after RBC transfusion is associated with an increase in PI. In addition, we assessed the value of PI and clinical measures in predicting the effect of RBC transfusion on IH.

STUDY DESIGN AND METHODS

We prospectively enrolled infants less than 30 weeks' gestation age. PI and oxygen saturation (SpO₂) …

Interrupted Time Series Design To Evaluate The Effect Of The Icd-9-Cm To Icd-10-Cm Coding Transition On Injury Hospitalization Trends, Svetla Slavova, Julia F. Costich, Huong Luu, Judith Fields, Barbara A. Gabella, Sergey Tarima, Terry L. Bunn

Biostatistics Faculty Publications

Background: Implementation of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) in the U.S. on October 1, 2015 was a significant policy change with the potential to affect established injury morbidity trends. This study used data from a single state to demonstrate 1) the use of a statistical method to estimate the effect of this coding transition on injury hospitalization trends, and 2) interpretation of significant changes in injury trends in the context of the structural and conceptual differences between ICD-9-CM and ICD-10-CM, the new ICD-10-CM-specific coding guidelines, and proposed ICD-10-CM-based framework for reporting of injuries by intent …

Association Analyses Of Repeated Measures On Triglyceride And High-Density Lipoprotein Levels: Insights From Gaw20, Saurabh Ghosh, David W. Fardo

Biostatistics Faculty Publications

Background: The GAW20 group formed on the theme of methods for association analyses of repeated measures comprised 4sets of investigators. The provided “real” data set included genotypes obtained from a human whole-genome association study based on longitudinal measurements of triglycerides (TGs) and high-density lipoprotein in addition to methylation levels before and after administration of fenofibrate. The simulated data set contained 200 replications of methylation levels and posttreatment TGs, mimicking the real data set.

Results: The different investigators in the group focused on the statistical challenges unique to family-based association analyses of phenotypes measured longitudinally and applied a wide spectrum of …

Gaw20: Methods And Strategies For The New Frontiers Of Epigenetics And Pharmacogenomics, Nathan L. Tintle, David W. Fardo, Marzia De Andrade, Stella Aslibekyan, Julia N. Bailey, Justo Lorenzo Bermejo, Rita M. Cantor, Saurabh Ghosh, Philip Melton, Xuexua Wang, Jean W. Maccluer, Laura Almasy

Biostatistics Faculty Publications

GAW20 provided a platform for developing and evaluating statistical methods to analyze human lipid-related phenotypes, DNA methylation, and single-nucleotide markers in a study involving a pharmaceutical intervention. In this article, we present an overview of the data sets and the contributions analyzing these data. The data, donated by the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) investigators, included data from 188 families (N = 1105) which included genome-wide DNA methylation data before and after a 3-week treatment with fenofibrate, single-nucleotide polymorphisms, metabolic syndrome components before and after treatment, and a variety of covariates. The contributions from individual …

Latent Tuberculosis Infection Is Associated With Increased Unstimulated Levels Of Interferon-Gamma In Lima, Peru, Moises A. Huaman, David Henson, Paola L. Rondan, Eduardo Ticona, Gustavo Miranda, Richard J. Kryscio, Raquel Mugruza, Ernesto Aranda, Cesar Ticona, Susan Abarca, Paula Heredia, Andres Aguirre, Timothy R. Sterling, Beth A. Garvy, Carl J. Fichtenbaum

Internal Medicine Faculty Publications

Background

We previously reported increased unstimulated blood levels of interferon-gamma in persons with latent tuberculosis infection (LTBI) in the United States, suggesting enhanced immune activation in LTBI. To investigate this further in a TB-endemic setting, we assessed interferon-gamma levels in persons with and without LTBI in Peru.

Methods

We analyzed data from patients with and without a recent type 1 (spontaneous) acute myocardial infarction (AMI) who were enrolled from two public hospital networks in Lima, Peru, and underwent LTBI testing using the QuantiFERON® TB Gold In-tube (QFT) assay. Participants with a positive QFT test were defined as having LTBI, whereas …

Neurotensin Receptor 3/Sortilin Contributes To Tumorigenesis Of Neuroendocrine Tumors Through Augmentation Of Cell Adhesion And Migration, Ji Tae Kim, Dana L. Napier, Heidi L. Weiss, Eun Y. Lee, Courtney M. Townsend, B. Mark Evers

Markey Cancer Center Faculty Publications

Neurotensin (NTS), a 13–amino acid peptide which is distributed predominantly along gastrointestinal tract, has multiple physiologic and pathologic functions, and its effects are mediated by three distinct NTS receptors (NTSRs). Overexpression and activation of NTS signaling components, especially NTS and/or NTSR1, are closely linked with cancer progression and metastasis in various types of cancers including neuroendocrine tumors (NETs). Although deregulation of NTSR3/sortilin has been implicated in a variety of human diseases, the expression and role of NTSR3/sortilin in NETs have not been elucidated. In this study, we investigated the expression and oncogenic effect of NTSR3/sortilin in NETs. Increased protein levels …

Treatment And Outcomes Of Non-Small-Cell Lung Cancer Patients With High Comorbidity, Jorge Rios, Rahul Gosain, Bernardo H. L. Goulart, Bin Huang, Margaret N. Oechsli, Jaclyn K. Mcdowell, Quan Chen, Thomas Tucker, Goetz H. Kloecker

Biostatistics Faculty Publications

Background: The life expectancy of untreated non-small-cell lung cancer (NSCLC) is dismal, while treatment for NSCLC improves survival. The presence of comorbidities is thought to play a significant role in the decision to treat or not treat a given patient. We aim to evaluate the association of comorbidities with the survival of patients treated for NSCLC.

Methods: We performed a retrospective study of patients aged ≥66 years with invasive NSCLC between the years 2007 and 2011 in the Surveillance, Epidemiology, and End Results Kentucky Cancer Registry. Comorbidity was measured using the Klabunde Comorbidity Index (KCI), and univariate and multivariate logistic …

Aggressive Diuresis And Severity-Adjusted Length Of Hospital Stay In Acute Congestive Heart Failure Patients, Muhammad U. Butt

Theses and Dissertations--Clinical Research Design

To see if aggressive diuresis in first twenty four hours is associated with a comparable number of total days in the hospital as compared to non-aggressive diuresis. In this retrospective cohort study, we compared the length of hospital stay of consecutive patients admitted in one year based on their diuresis during the first twenty-four hours of hospitalization: aggressive diuresis (group 1) i.e. > 2400mL versus non-aggressive diuresis (group 2) i.e. ≤ 2400mL urine output. Patients were excluded if in cardiogenic shock, had creatinine level above 3 mg/dL on admission, or on dialysis. A total of 194 patients were enrolled (29 in …

Bivariate Generalization Of The Time-To-Event Conditional Reassessment Method With A Novel Adaptive Randomization Method, Donglin Yan

Theses and Dissertations--Epidemiology and Biostatistics

Phase I clinical trials in oncology aim to evaluate the toxicity risk of new therapies and identify a safe but also effective dose for future studies. Traditional Phase I trials of chemotherapies focus on estimating the maximum tolerated dose (MTD). The rationale for finding the MTD is that better therapeutic effects are expected at higher dose levels as long as the risk of severe toxicity is acceptable. With the advent of a new generation of cancer treatments such as the molecularly targeted agents (MTAs) and immunotherapies, higher dose levels no longer guarantee increased therapeutic effects, and the focus has shifted …

Improved Methods And Selecting Classification Types For Time-Dependent Covariates In The Marginal Analysis Of Longitudinal Data, I-Chen Chen

Theses and Dissertations--Epidemiology and Biostatistics

Generalized estimating equations (GEE) are popularly utilized for the marginal analysis of longitudinal data. In order to obtain consistent regression parameter estimates, these estimating equations must be unbiased. However, when certain types of time-dependent covariates are presented, these equations can be biased unless an independence working correlation structure is employed. Moreover, in this case regression parameter estimation can be very inefficient because not all valid moment conditions are incorporated within the corresponding estimating equations. Therefore, approaches using the generalized method of moments or quadratic inference functions have been proposed for utilizing all valid moment conditions. However, we have found that …

Using Prescription Drug Monitoring Data To Inform Population Level Analysis Of Opioid Analgesic Utilization, Huong T. T. Luu

Theses and Dissertations--Epidemiology and Biostatistics

Increased opioid analgesic (OA) prescribing has been associated with increased risk of prescription opioid diversion, misuse, and abuse. States established prescription drug monitoring programs (PDMPs) to collect and analyze electronic records for dispensed controlled substances to reduce prescription drug abuse and diversion. PDMP data can be used by prescribers for tracking patient’s history of controlled substance prescribing to inform clinical decisions.

The studies in this dissertation are focused on the less utilized potential of the PDMP data to enhance public health surveillance to monitor OA prescribing and co-prescribing and association with opioid overdose mortality and morbidity. Longitudinal analysis of OA …

Improved Standard Error Estimation For Maintaining The Validities Of Inference In Small-Sample Cluster Randomized Trials And Longitudinal Studies, Whitney Ford Tanner

Theses and Dissertations--Epidemiology and Biostatistics

Data arising from Cluster Randomized Trials (CRTs) and longitudinal studies are correlated and generalized estimating equations (GEE) are a popular analysis method for correlated data. Previous research has shown that analyses using GEE could result in liberal inference due to the use of the empirical sandwich covariance matrix estimator, which can yield negatively biased standard error estimates when the number of clusters or subjects is not large. Many techniques have been presented to correct this negative bias; However, use of these corrections can still result in biased standard error estimates and thus test sizes that are not consistently at their …