Biostatistics Commons^™

Genetic Contributors Of Incident Stroke In 10,700 African Americans With Hypertension: A Meta-Analysis From The Genetics Of Hypertension Associated Treatments And Reasons For Geographic And Racial Differences In Stroke Studies, Nicole D. Armstrong, Vinodh Srinivasasainagendra, Amit Patki, Rikki M. Tanner, Bertha A. Hidalgo, Hemant K. Tiwari, Nita A. Limdi, Ethan M. Lange, Leslie A. Lange, Donna K. Arnett, Marguerite R. Irvin

Epidemiology and Environmental Health Faculty Publications

Background: African Americans (AAs) suffer a higher stroke burden due to hypertension. Identifying genetic contributors to stroke among AAs with hypertension is critical to understanding the genetic basis of the disease, as well as detecting at-risk individuals.

Methods: In a population comprising over 10,700 AAs treated for hypertension from the Genetics of Hypertension Associated Treatments (GenHAT) and Reasons for Geographic and Racial Differences in Stroke (REGARDS) studies, we performed an inverse variance-weighted meta-analysis of incident stroke. Additionally, we tested the predictive accuracy of a polygenic risk score (PRS) derived from a European ancestral population in both GenHAT and REGARDS AAs …

The Efficacy Of Plant-Based Dietary Program In Patients With Diabetes: A Pilot Study, Reuben Adatorwovor, Nisha Sharma, Dakota Mccoy, Sharon Wasserstrom, Matthew Robinson, Jacquelyn Nyenhuis, Sowmya Suryanarayanan

Biostatistics Faculty Publications

Dietary choices play a key role in insulin sensitivity among diabetes patients. An 8-week pilot study was conducted to evaluate whether a mostly plant-based dietary program will lead to improvement in biochemical markers in adults with diabetes. The dietary program included educational presentations, weekly cooking demonstrations and small group discussions. A sample of thirty-two adults with diabetes (types 1 and 2) were recruited and seventeen (53%) completed the study. Matched-pair tests and Fishers exact tests were used to compare the changes in means and proportion of the participants’ responses. There were changes in HbA1c, lipids, CRP (mg/L), cholesterol (mg/dL), HDL …

Characterizing Long Covid: Deep Phenotype Of A Complex Condition, Rachel R. Deer, Madeline A. Rock, Nicole Vasilevsky, Leigh Carmody, Halie Rando, Alfred J. Anzalone, Marc D. Basson, Tellen D. Bennett, Timothy Bergquist, Eilis A. Boudreau, Carolyn T. Bramante, James Brian Byrd, Tiffany J. Callahan, Lauren E. Chan, Haitao Chu, Christopher G. Chute, Ben D. Coleman, Hannah E. Davis, Joel Gagnier, Casey S. Greene, Ramakanth Kavuluru

Institute for Biomedical Informatics Faculty Publications

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies.

METHODS: The Human Phenotype Ontology …

Ovarian Cancer Epidemiology, Healthcare Access And Disparities (Orchid): Methodology For A Population-Based Study Of Black, Hispanic And White Patients With Ovarian Cancer, Tomi Akinyemiju, April Deveaux, Lauren Wilson, Anjali Gupta, Ashwini Joshi, Malcolm Bevel, Chioma Omeogu, Onyinye Ohamadike, Bin Huang, Maria Pisu, Margaret Liang, Molly Mcfatrich, Erin Daniell, Laura Jane Fish, Kevin Ward, Maria Schymura, Andrew Berchuck, Arnold L. Potosky

Biostatistics Faculty Publications

INTRODUCTION: Less than 40% of patients with ovarian cancer (OC) in the USA receive stage-appropriate guideline-adherent surgery and chemotherapy. Black patients with cancer report greater depression, pain and fatigue than white patients. Lack of access to healthcare likely contributes to low treatment rates and racial differences in outcomes. The Ovarian Cancer Epidemiology, Healthcare Access and Disparities study aims to characterise healthcare access (HCA) across five specific dimensions-Availability, Affordability, Accessibility, Accommodation and Acceptability-among black, Hispanic and white patients with OC, evaluate the impact of HCA on quality of treatment, supportive care and survival, and explore biological mechanisms that may contribute to …

The Mediating/Moderating Role Of Cultural Context Factors On Self-Care Practices Among Those Living With Diabetes In Rural Appalachia, Brittany L. Smalls, Adebola Adegboyega, Ellen Combs, Matthew Rutledge, Philip M. Westgate, Md. Tofial Azam, Felipe De La Barra, Lovoria B. Williams, Nancy E. Schoenberg

Family and Community Medicine Faculty Publications

Background

The aim of this study was to examine whether cultural factors, such as religiosity and social support, mediate/moderate the relationship between personal/psychosocial factors and T2DM self-care in a rural Appalachian community.

Methods

Regression models were utilized to assess for mediation and moderation. Multilevel linear mixed effects models and GEE-type logistic regression models were fit for continuous (social support, self-care) and binary (religiosity) outcomes, respectively.

Results

The results indicated that cultural context factors (religiosity and social support) can mediate/moderate the relationship between psychosocial factors and T2DM self-care. Specifically, after adjusting for demographic variables, the findings suggested that social support may …

Analysis Of Genes (Tmem106b, Grn, Abcc9, Kcnmb2, And Apoe) Implicated In Risk For Late-Nc And Hippocampal Sclerosis Provides Pathogenetic Insights: A Retrospective Genetic Association Study, Adam J. Dugan, Peter T. Nelson, Yuriko Katsumata, Lincoln M. P. Shade, Kevin L. Boehme, Merilee A. Teylan, Matthew D. Cykowski, Shubhabrata Mukherjee, John S. K. Kauwe, Timothy J. Hohman, Julie A. Schneider, Alzheimer’S Disease Genetics Consortium, David W. Fardo

Biostatistics Faculty Publications

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is the most prevalent subtype of TDP-43 proteinopathy, affecting up to 1/3rd of aged persons. LATE-NC often co-occurs with hippocampal sclerosis (HS) pathology. It is currently unknown why some individuals with LATE-NC develop HS while others do not, but genetics may play a role. Previous studies found associations between LATE-NC phenotypes and specific genes: TMEM106B, GRN, ABCC9, KCNMB2, and APOE. Data from research participants with genomic and autopsy measures from the National Alzheimer’s Coordinating Center (NACC; n = 631 subjects included) and the Religious Orders Study and Memory …

Hiv Infection And The Risk Of World Health Organization-Defined Sudden Cardiac Death, Matthew S. Freiberg, Meredith S. Duncan, Charles Alcorn, Chung-Chou H. Chang, Suman Kundu, Asri Mumpuni, Emily K. Smith, Sarah Loch, Annie Bedigian, Eric Vittinghoff, Kaku So-Armah, Priscilla Y. Hsue, Amy C. Justice, Zian H. Tseng

Biostatistics Faculty Publications

Background

People living with HIV have higher sudden cardiac death (SCD) rates compared with the general population. Whether HIV infection is an independent SCD risk factor is unclear.

Methods and Results

This study evaluated participants from the Veterans Aging Cohort Study, an observational, longitudinal cohort of veterans with and without HIV infection matched 1:2 on age, sex, race/ethnicity, and clinical site. Baseline for this study was a participant's first clinical visit on or after April 1, 2003. Participants were followed through December 31, 2014. Using Cox proportional hazards regression, we assessed whether HIV infection, CD4 cell counts, and/or HIV viral …

A Randomized Controlled Trial To Determine Whether Beta-Hydroxy-Beta-Methylbutyrate And/Or Eicosapentaenoic Acid Improves Diaphragm And Quadriceps Strength In Critically Ill Mechanically Ventilated Patients, Gerald S. Supinski, Paul F. Netzel, Philip M. Westgate, Elizabeth A. Schroder, Lin Wang, Leigh Ann Callahan

Internal Medicine Faculty Publications

BACKGROUND: Intensive care unit acquired weakness is a serious problem, contributing to respiratory failure and reductions in ambulation. Currently, there is no pharmacological therapy for this condition. Studies indicate, however, that both beta-hydroxy-beta-methylbutyrate (HMB) and eicosapentaenoic acid (EPA) increase muscle function in patients with cancer and in older adults. The purpose of this study was to determine whether HMB and/or EPA administration would increase diaphragm and quadriceps strength in mechanically ventilated patients.

METHODS: Studies were performed on 83 mechanically ventilated patients who were recruited from the Medical Intensive Care Units at the University of Kentucky. Diaphragm strength was assessed as …

Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids To Predict Carboplatin Resistance, Justin W. Gorski, Zhuwei Zhang, J. Robert Mccorkle, Jodi M. Dejohn, Chi Wang, Rachel W. Miller, Holly H. Gallion, Charles S. Dietrich Iii, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

The development of patient-derived tumor organoids (TOs) from an epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine. Here, we utilized TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high-grade, serous epithelial ovarian cancer tumor organoid lines from tissue obtained during debulking surgery (two neoadjuvant-carboplatin-exposed and four chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1, and 0.1 µM). Cell viability curves and resultant EC₅₀ values …

Lapatinib And Poziotinib Overcome Abcb1-Mediated Paclitaxel Resistance In Ovarian Cancer, J. Robert Mccorkle, Justin W. Gorski, Jinpeng Liu, Mckayla J. Riggs, Anthony B. Mcdowell Jr., Nan Lin, Chi Wang, Frederick R. Ueland, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Conventional frontline treatment for ovarian cancer consists of successive chemotherapy cycles of paclitaxel and platinum. Despite the initial favorable responses for most patients, chemotherapy resistance frequently leads to recurrent or refractory disease. New treatment strategies that circumvent or prevent mechanisms of resistance are needed to improve ovarian cancer therapy. We established in vitro paclitaxel-resistant ovarian cancer cell line and organoid models. Gene expression differences in resistant and sensitive lines were analyzed by RNA sequencing. We manipulated candidate genes associated with paclitaxel resistance using siRNA or small molecule inhibitors, and then screened the cells for paclitaxel sensitivity using cell viability assays. …

Clinical Outcomes Of Molecular Tumor Boards: A Systematic Review, Kara L. Larson, Bin Huang, Heidi L. Weiss, Pamela C. Hull, Philip M. Westgate, Rachel W. Miller, Susanne M. Arnold, Jill M. Kolesar

Markey Cancer Center Faculty Publications

PURPOSE: We conducted this systematic review to evaluate the clinical outcomes associated with molecular tumor board (MTB) review in patients with cancer.

METHODS: A systematic search of PubMed was performed to identify studies reporting clinical outcomes in patients with cancer who were reviewed by an MTB. To be included, studies had to report clinical outcomes, including clinical benefit, response, progression-free survival, or overall survival. Two reviewers independently selected studies and assessed quality with the Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group or the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies depending on the type …

Covid-19 And The Impact On Rural And Black Church Congregants: Results Of The C-M-C Project, Lovoria B. Williams, Anita F. Fernander, Tofial Azam, Maria L. Gomez, Junghee Kang, Cassidy L. Moody, Hannah Bowman, Nancy E. Schoenberg

Nursing Faculty Publications

The COVID-19 pandemic has had devastating effects on Black and rural populations with a mortality rate among Blacks three times that of Whites and both rural and Black populations experiencing limited access to COVID-19 resources. The primary purpose of this study was to explore the health, financial, and psychological impact of COVID-19 among rural White Appalachian and Black nonrural central Kentucky church congregants. Secondarily we sought to examine the association between sociodemographics and behaviors, attitudes, and beliefs regarding COVID-19 and intent to vaccinate. We used a cross sectional survey design developed with the constructs of the Health Belief and Theory …

Analysis Of Genetic Variants Associated With Levels Of Immune Modulating Proteins For Impact On Alzheimer’S Disease Risk Reveal A Potential Role For Siglec14, Benjamin C. Shaw, Yuriko Katsumata, James F. Simpson, David W. Fardo, Steven Estus

Biostatistics Faculty Publications

Genome-wide association studies (GWAS) have identified immune-related genes as risk factors for Alzheimer’s disease (AD), including TREM2 and CD33, frequently passing a stringent false-discovery rate. These genes either encode or signal through immunomodulatory tyrosine-phosphorylated inhibitory motifs (ITIMs) or activation motifs (ITAMs) and govern processes critical to AD pathology, such as inflammation and amyloid phagocytosis. To investigate whether additional ITIM and ITAM-containing family members may contribute to AD risk and be overlooked due to the stringent multiple testing in GWAS, we combined protein quantitative trait loci (pQTL) data from a recent plasma proteomics study with AD associations in a recent …

A Highly Predictive Microrna Panel For Determining Delayed Cerebral Vasospasm Risk Following Aneurysmal Subarachnoid Hemorrhage, Wang-Xia Wang, Joe E. Springer, Kevin Xie, David W. Fardo, Kevin W. Hatton

Sanders-Brown Center on Aging Faculty Publications

Approximately one-third of aneurysmal subarachnoid hemorrhage (aSAH) patients develop delayed cerebral vasospasm (DCV) 3–10 days after aneurysm rupture resulting in additional, permanent neurologic disability. Currently, no validated biomarker is available to determine the risk of DCV in aSAH patients. MicroRNAs (miRNAs) have been implicated in virtually all human diseases, including aSAH, and are found in extracellular biofluids including plasma and cerebrospinal fluid (CSF). We used a custom designed TaqMan Low Density Array miRNA panel to examine the levels of 47 selected brain and vasculature injury related miRNAs in CSF and plasma specimens collected from 31 patients with or without DCV …

An Ensemble Of The Icluster Method To Analyze Longitudinal Lncrna Expression Data For Psoriasis Patients, Suyan Tian, Chi Wang

Internal Medicine Faculty Publications

BACKGROUND: Psoriasis is an immune-mediated, inflammatory disorder of the skin with chronic inflammation and hyper-proliferation of the epidermis. Since psoriasis has genetic components and the diseased tissue of psoriasis is very easily accessible, it is natural to use high-throughput technologies to characterize psoriasis and thus seek targeted therapies. Transcriptional profiles change correspondingly after an intervention. Unlike cross-sectional gene expression data, longitudinal gene expression data can capture the dynamic changes and thus facilitate causal inference.

METHODS: Using the iCluster method as a building block, an ensemble method was proposed and applied to a longitudinal gene expression dataset for psoriasis, with the …

Validation Of Icd-10-Cm Codes For Injuries Complicating Pregnancy, Childbirth And The Puerperium: A Medical Record Review, Anna Hansen, Dana Quesinberry, Peter Akpunonu, Julia Martin, Svetla Slavova

Kentucky Injury Prevention and Research Center Faculty Publications

INTRODUCTION: The purpose of this study was to estimate the positive predictive value (PPV) of International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes for injury, poisoning, physical or sexual assault complicating pregnancy, childbirth and the puerperium (PCP) to capture injury encounters within both hospital and emergency department claims data.

METHODS: A medical record review was conducted on a sample (n=157) of inpatient and emergency department claims from one Kentucky healthcare system from 2015 to 2017, with any diagnosis in the ICD-10-CM range O9A.2-O9A.4. Study clinicians reviewed medical records for the sampled cases and used an abstraction form to …

Real World Clinicopathologic Observations Of Patients With Metastatic Solid Tumors Receiving Immune Checkpoint Inhibitor Therapy: Analysis From Kentucky Cancer Registry, Aasems Jacob, Jianrong Wu, Jill M. Kolesar, Eric B. Durbin, Aju Mathew, Susanne Arnold, Aman Chauhan

Biostatistics Faculty Publications

The state of Kentucky has the highest cancer incidence and mortality in the United States. High‐risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution.

Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure …