The Role Of Psychosocial Factors On Pre And Postoperative Pain In Patients With Femoral Acetabular Impingement, Kate N. Jochimsen

Theses and Dissertations--Rehabilitation Sciences

Femoral acetabular impingement (FAI) is a bony hip condition that often results in tears to the acetabular labrum. Patients with FAI experience pain, decreased function, and quality of life. FAI and its’ sequela are treated definitively with hip arthroscopy. Hip arthroscopy is being performed with increasing frequency, and while most patients respond favorably, a subset of 10-20% of patients have suboptimal outcomes.

Previous research suggests that mental status may be a primary driver in the way patients with FAI respond to and feel pain. Measures of mental status include the presence of mood disorders and psychosocial patient reported outcomes (PROs). …

Role Of Sex Chromosomes In Sexual Dimorphism Of Angii-Induced Abdominal Aortic Aneurysms, Yasir Alsiraj

Theses and Dissertations--Pharmacology and Nutritional Sciences

Abdominal aortic aneurysms (AAAs), a permanent dilation in the abdominal region of the aorta, is a highly sexually dimorphic disease. AAAs prevalence is ranging from 4-10 fold higher in males than females. Defining the mechanistic basis for reduced (in females) or increased (in males) AAA formation and progression may uncover potential therapeutic targets. The majority of studies examining sexual dimorphism focus on the role of sex hormones. However, genes residing on sex chromosomes, in addition to sex hormones, may contribute to sexual dimorphism of AAAs. For example, the X chromosome contains about 5% of the whole genome, but the role …

Healthcare Providers’ Perceptions Of Pregnant Women, Allison Goderwis

Theses and Dissertations--Family Sciences

Health care providers’ (N = 421) implicit perceptions of pregnant women based on age, race or ethnicity, marital status, and socioeconomic status are assessed through a true-experiment design. Ordinal and binary regression analyses revealed that respondents felt more pity for an unmarried than married pregnant woman and more anger toward an unemployed pregnant woman without health insurance compared to a pregnant woman who was employed with health insurance. Male, Asian, and Hispanic respondents were less likely to help the pregnant woman, Black and protestant respondents were more likely to express some degree of anger toward the pregnant woman, and …

Impact Of Advanced Practice Providers (App) Care Models And Outcomes In Primary Care, Kathleen Exline

DNP Projects

Background: The Affordable Care Act, an aging population, and the increased burden of caring for the chronically ill are factors that have resulted in a significantly increased demand on primary care. This has prompted the strategy to utilize advanced practice providers (APPs) to supplement primary care physicians. Due to the inconsistency of a defined national model and measurement system, the impact of APP utilization in healthcare is not clear.

Purpose: The purpose of this project was to examine the use of APPs in primary care. The study involved a review of the current utilization of APPs, an evaluation of the …

Down Syndrome, Beta-Amyloid And Neuroimaging, Elizabeth Head, Alex M. Helman, David K. Powell, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

This review focuses on the role of Aβ in AD pathogenesis in Down syndrome and current approaches for imaging Aβ in vivo. We will describe how Aβ deposits with age, the posttranslational modifications that can occur, and detection in biofluids. Three unique case studies describing partial trisomy 21 cases without APP triplication, and the occurrences of low level mosaic trisomy 21 in an early onset AD patient are presented. Brain imaging for Aβ includes those by positron emission tomography and ligands (Pittsburgh Compound B, Florbetapir, and FDDNP) that bind Aβ have been published and are summarized here. In combination, we …

Tumor Microvessel Density As A Prognostic Marker In High-Risk Renal Cell Carcinoma Patients Treated On Ecog-Acrin E2805, Lucia B. Jilaveanu, Maneka Puligandla, Sarah A. Weiss, Xin Victoria Wang, Christopher Zito, Keith T Flaherty, Marta Boeke, Veronique Neumeister, Robert L. Camp, Adebowale Adeniran, Michael Pins, Judith Manola, Robert S. Dipaola, Naomi B. Haas, Harriet M. Kluger

Internal Medicine Faculty Publications

Purpose—Increased vascularity is a hallmark of renal cell carcinoma (RCC). Microvessel density (MVD) is one measurement of tumor angiogenesis; however, its utility as a biomarker of outcome is unknown. ECOG-ACRIN 2805 (E2805) enrolled 1,943 resected high-risk RCC patients randomized to adjuvant sunitinib, sorafenib, or placebo. We aimed to determine the prognostic and predictive role of MVD in RCC.

Experimental Design—We obtained pretreatment primary RCC nephrectomy tissues from 822 patients on E2805 and constructed tissue microarrays. Using quantitative immunofluorescence, we measured tumor MVD as the area of CD34-expressing cells. We determined the association with disease-free survival (DFS), overall survival …

Improvement In Diagnosis Of Histoplasma Meningitis By Combined Testing For Histoplasma Antigen And Immunoglobulin G And Immunoglobulin M Anti-Histoplasma Antibody In Cerebrospinal Fluid, Karen C. Bloch, Thein Myint, Luke Raymond-Guillen, Chadi A. Hage, Thomas E. Davis, Patty W. Wright, Felicia C. Chow, Laila Woc-Colburn, Raed N. Khairy, Alan C. Street, Tomotaka Yamamoto, Amanda Albers, L Joseph Wheat

Internal Medicine Faculty Publications

Background. Central nervous system (CNS) histoplasmosis is a life-threatening condition and represents a diagnostic and therapeutic challenge. Isolation of Histoplasma capsulatum from cerebrospinal fluid (CSF) or brain tissue is diagnostic; however, culture is insensitive and slow growth may result in significant treatment delay. We performed a retrospective multicenter study to evaluate the sensitivity and specificity of a new anti-Histoplasma antibody enzyme immunoassay (EIA) for the detection of IgG and IgM antibody in the CSF for diagnosis of CNS histoplasmosis, the primary objective of the study. The secondary objective was to determine the effect of improvements in the Histoplasma galactomannan …

Mechanisms And Potential Therapy On Disrupted Blood Pressure Circadian Rhythm In Diabetes, Tianfei Hou

Theses and Dissertations--Pharmacology and Nutritional Sciences

Arterial blood pressure (BP) undergoes a 24-hour oscillation that peaks in the active day and reaches a nadir at night during sleep in humans. Reduced nocturnal BP fall (also known as non-dipper) is the most common disruption of BP circadian rhythm and is associated with increased risk of untoward cardiovascular events and target organ injury. Up to 75% of diabetic patients are non-dippers. However, the mechanisms underlying diabetes associated non-dipping BP are largely unknown. To address this important question, we generated a novel diabetic db/db-mPer2^Luc mouse model (db/db-mPer2^Luc) that allows quantitatively measuring of mPER2 protein oscillation …

The Effect Of A Single-Session Group Songwriting Intervention On Grief Processing In Hospice Clinicians, Melissa Deaton

Theses and Dissertations--Music

The purpose of this study was to determine the effect of a single-session group music therapy songwriting session on grief processing in hospice clinicians. The study design was quasi-experimental. Participants were cluster randomized into a control group and a treatment group. The researcher led a 50-minute songwriting session focused on sharing and processing experiences of grief-related stress and burnout in hospice work. Grief processing was measured using a self-report survey for n=25. Overall differences between control and treatment groups were not found to be statistically significant. Significant differences were also not found in treatment score differences for type of …

Intra-Arterial Nitroglycerin As Directed Acute Treatment In Experimental Ischemic Stroke, Michael E. Maniskas, Jill M. Roberts, Rebecca Trueman, Annastazia E. Learoyd, Amanda A. Gorman, Justin F. Fraser, Gregory J. Bix

Neuroscience Faculty Publications

BACKGROUND: Nitroglycerin (also known as glyceryl trinitrate (GTN)), a vasodilator best known for treatment of ischemic heart disease, has also been investigated for its potential therapeutic benefit in ischemic stroke. The completed Efficacy of Nitric Oxide in Stroke trial suggested that GTN has therapeutic benefit with acute (within 6 hours) transdermal systemic sustained release therapy.

OBJECTIVE: To examine an alternative use of GTN as an acute therapy for ischemic stroke following successful recanalization.

METHODS: We administered GTN IA following transient middle cerebral artery occlusion in mice. Because no standard dose of GTN is available following emergent large vessel occlusion, we …

Genotype-Phenotype Study In Patients With Valosin-Containing Protein Mutations Associated With Multisystem Proteinopathy, Ebaa Al-Obeidi, Sejad Al-Tahan, Abhilasha Surampalli, Namita Goyal, Annabel K. Wang, Andreas Hermann, Molly Omizo, Charles D. Smith, Tahseen Mozaffar, Virginia Kimonis

Neurology Faculty Publications

Mutations in valosin‐containing protein (VCP), an ATPase involved in protein degradation and autophagy, cause VCP disease, a progressive autosomal dominant adult onset multisystem proteinopathy. The goal of this study is to examine if phenotypic differences in this disorder could be explained by the specific gene mutations. We therefore studied 231 individuals (118 males and 113 females) from 36 families carrying 15 different VCP mutations. We analyzed the correlation between the different mutations and prevalence, age of onset and severity of myopathy, Paget's disease of bone (PDB), and frontotemporal dementia (FTD), and other comorbidities. Myopathy, PDB and FTD was present in …

Serum Tumor Necrosis Factor-Alpha Associates With Myocardial Oxygen Demand And Exercise Tolerance In Postmenopausal Women, Stephen J. Carter, David R. Bryan, William H. Neumeier, Stephen P. Glasser, Gary R. Hunter

Internal Medicine Faculty Publications

The functional implications of serum tumor necrosis factor-alpha (TNF-α), a marker of oxidative stress, on hemodynamic parameters at rest and during physical exertion are unclear. The aims of this investigation were to examine the independent associations of TNF-α on myocardial oxygen demand at rest and during submaximal exercise, while also evaluating the association of TNF-α on exercise tolerance. Forty, postmenopausal women, provided blood samples and completed a modified-Balke protocol to measure maximal oxygen uptake (VO_2max). Large artery compliance was measured by pulse contour analyses while rate-pressure product (RPP), an index of myocardial oxygen demand, was measured at rest …

Cetuximab Plus Carboplatin And Paclitaxel With Or Without Bevacizumab Versus Carboplatin And Paclitaxel With Or Without Bevacizumab In Advanced Nsclc (Swog S0819): A Randomised, Phase 3 Study, Roy S. Herbst, Mary W. Redman, Edward S. Kim, Thomas J. Semrad, Lyudmila Bazhenova, Gregory Masters, Kurt Oettel, Perry Guaglianone, Christopher Reynolds, Anand Karnad, Susanne M. Arnold, Marileila Varella-Garcia, James Moon, Philip C. Mack, Charles D. Blanke, Fred R. Hirsch, Karen Kelly, David R. Gandara

Markey Cancer Center Faculty Publications

Background

EGFR antibodies have shown promise in patients with advanced non-small-cell lung cancer (NSCLC), particularly with squamous cell histology. We hypothesised that EGFR copy number by fluorescence in-situ hybridisation (FISH) can identify patients most likely to benefit from these drugs combined with chemotherapy and we aimed to explore the activity of cetuximab with chemotherapy in patients with advanced NSCLC who are EGFR FISH-positive.

Methods

We did this open-label, phase 3 study (SWOG S0819) at 277 sites in the USA and Mexico. We randomly assigned (1:1) eligible patients with treatment-naive stage IV NSCLC to receive paclitaxel (200 mg/m ²; every …

Nanoparticle Orientation To Control Rna Loading And Ligand Display On Extracellular Vesicles For Cancer Regression, Fengmei Pi, Daniel W. Binzel, Tae Jin Lee, Zhefeng Li, Meiyan Sun, Piotr G. Rychahou, Hui Li, Farzin Haque, Shaoying Wang, Carlo M. Croce, Bin Guo, B. Mark Evers, Peixuan Guo

Markey Cancer Center Faculty Publications

Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the extracellular vesicles. Taking advantage of the RNA ligand for …

Evaluating The Effectiveness Of Norton Cancer Institute’S Prompt Care Clinics, Stephanie L. Fred

DNP Projects

Purpose: The purpose of this project was to evaluate outcomes of implementation of the Norton Cancer Institute (NCI) Prompt Care Clinics (PCCs), to include number of emergency room (ER) visits and number of inpatient admissions. A second purpose of the study was to identify presenting symptoms for patients seen in the NCI PCCs and compare the average charge per case for patients seen in the ER or NCI PCCs with the same diagnosis.

Methods: This study employed a pre-post implementation retrospective review of NCI patient electronic medical records (EPIC) to examine the effectiveness of the NCI PCCs on …

Evaluation Outcomes Of A Modified Early Warning System For Early Identification Of Sepsis In The Adult Population Requiring Acute Care, Gavin M. Turpin

DNP Projects

Objectives: To examine the use of a Modified Early Warning System (MEWS) for sepsis identification and evaluate its effects on treatment and outcomes for those patients diagnosed with sepsis after admission, during their stay at an acute care facility.

Design: A retrospective chart audit was conducted on the electronic medical records (EMRs) of patients who developed, and were diagnosed with, sepsis post admission. Specifically, a retrospective separate sample pretest posttest design was used to examine the accuracy of the MEWS, differences in outcomes (ICU days, length of hospital stay, qSOFA Score and mortality rates), and treatment initiation time (fluid resuscitation, …

Assessment Of The Need For Provider Education On Screening For Depression In Patients With Select Dermatologic Problems, Sarah B. Zerhusen

DNP Projects

PURPOSE: The purpose of this project is to evaluate the knowledge, attitudes, perceptions, skills, and self-efficacy of dermatology providers’ assessment of depression in patients with chronic skin disease to determine the need for continuing education programs.

METHODS: This is a single practice, multi site, quantitative correlational design study to assess provider use, comfort, and proficiency of screening and discussion of depression in patients suffering from plaque psoriasis and atopic dermatitis. Data was collected through the use of a questionnaire dispensed in January of 2018. The sample consisted of 23 dermatology providers in a dermatology practice with clinics in Louisville, Lebanon, …

The Effect Of A School-Based Health Center On Access To Care In A Rural Community, Macey Cornwell

DNP Projects

BACKGROUND: Lack of access to healthcare is a nationwide issue that affects underserved, minority, and rural populations. School-Based Health Centers (SBHCs) is one way to help increase access to care for students, staff, and family members.

PURPOSE: The purpose of this project was to provide preliminary data on the impact of a SBHC in a rural Kentucky community on access to care and school attendance.

METHODS: A univariate descriptive analysis was conducted to evaluate the perceived impact of the SBHC on access to care and demographic factors. Data was analyzed using Pearson’s Product Moment Correlation, two-sample t-tests, and The Wilcoxon …

An Assessment To Determine The Need For A Palliative Care Team To Improve Patient Satisfaction And Decrease Healthcare Costs, Nathalie Weis

DNP Projects

Abstract

Objective: The purpose of this project was to determine if there is a need for a palliative care team (PCT) to which primary care medical professionals can refer patients. The specific objectives of this project were: 1. To assess the knowledge of primary care providers regarding palliative care. 2. To assess the value and need for palliative care from the PCPs’ perspective. 3. To evaluate the current ED utilization data for adults with serious chronic illness.

Methods: This was a descriptive study that involved an analysis of ED visit data for chronic illness, and a survey all …

The Impact Of The Nurse Practitioner In Pre-Admission Testing: A Comparative Review, Laurel A. Robinson

DNP Projects

Abstract

PURPOSE: The purpose of this study was to compare the efficiency of pre-admission testing (PAT) surgical clinic pre and post implementation of the APRN for patient assessment. Cancellation and delay occurrences for scheduled surgeries will be compared during two time periods on patients on the surgical schedule at Norton Women and Children’s Hospital (NWC).

METHODS: This study was a single-center, pre and post implementation retrospective comparative study of the impact of the NP led PAT unit at Norton Women and Children’s Hospital (NWC) in terms of delay and cancellation rates for day-of-surgery. The sample consisted of 411 patients for …

Diabetes-Related Distress Screening: A Survey Of Primary Care Providers' Knowledge, Attitudes, And Practices In Treating Patients With Difficulty Meeting Glycemic Goals., Michele Patrice Paxton

DNP Projects

A patient with diabetes is two to three times more likely to be depressed than the general population. Furthermore, the combination of diabetes and depression is associated with increased morbidity and mortality. However, research has shown that treatment for depression does not correlate with lower HbA1c levels or a decrease in morbidity and mortality. Recently, a body of evidence has shown that increased HbA1c levels and depression are associated with the emotional burden of managing diabetes. The emotional burden is caused by the constant behavioral and mental demands of managing the disease and the worry and fear of the impending …

A Breast Prosthesis Infection Update: Two-Year Incidence, Risk Factors And Management At Single Institution, Ashley Nadia Boustany, Shady Elmaraghi, Nneamaka Agochukwu, Benjamin Cloyd, Adam J. Dugan, Brian Rinker

Surgery Faculty Publications

Background: Infection following augmentation and prosthetic-based breast reconstruction can cause significant physical and psychological distress for patients. It may delay adjuvant therapies and compromise aesthetic outcomes. The aim of this study is to identify modifiable risk factors for infection and identify common bacterial isolates to achieve optimal outcomes for patients.

Methods: A retrospective cohort study was performed for patients undergoing implant-based breast reconstruction over a 2-year period. In each case, we documented demographics, co-morbidities, complications and antibiotic use. We reviewed treatments, infectious species cultured where applicable and all outcomes.

Results: A total of 292 patients met the inclusion criteria. Fifty-five …

Discovery Of Novel, Orally Bioavailable, Antileishmanial Compounds Using Phenotypic Screening, Diana Ortiz, W. Armand Guiguemde, Jared T. Hammill, Angela K. Carrillo, Yizhe Chen, Michele Connelly, Kayla Stalheim, Carolyn Elya, Alex Johnson, Jaeki Min, Anang Shelat, David C. Smithson, Lei Yang, Fangyi Zhu, R. Kiplin Guy, Scott M. Landfear

Pharmaceutical Sciences Faculty Publications

Leishmaniasis is a parasitic infection that afflicts approximately 12 million people worldwide. There are several limitations to the approved drug therapies for leishmaniasis, including moderate to severe toxicity, growing drug resistance, and the need for extended dosing. Moreover, miltefosine is currently the only orally available drug therapy for this infection. We addressed the pressing need for new therapies by pursuing a two-step phenotypic screen to discover novel, potent, and orally bioavailable antileishmanials. First, we conducted a high-throughput screen (HTS) of roughly 600,000 small molecules for growth inhibition against the promastigote form of the parasite life cycle using the nucleic acid …

Ovarian Cancer Screening: Lessons About Effectiveness, Edward J. Pavlik

Obstetrics and Gynecology Faculty Publications

No abstract provided.

Immune Checkpoint Inhibitors In Neuroendocrine Tumors: A Single Institution Experience With Review Of Literature, Aman Chauhan, Millicent Horn, Gray Magee, Kurt Hodges, B. Mark Evers, Susanne Arnold, Lowell B. Anthony

Markey Cancer Center Faculty Publications

This unique case series and review of literature suggests that immune checkpoint inhibitors may have clinical activity in neuroendocrine tumors.

Objective: Summarize advances of immuno-oncology in neuroendocrine tumors with the help of a case series.

Design: Case series and review of literature.

Intervention or Exposure: The patients were treated with immune checkpoint inhibitors (pembrolizumab or nivolumab).

Main Outcome(s) and Measures(s): Life expectancy, quality of life, disease progression.

Results: Maximum durable response of 16 months in one of the patients so far. All patients showed improvement in quality of life before disease progression. Two out of four are still on therapy. …

An Investigation Of Factors Predicting The Type Of Bladder Antimuscarinics Initiated In Medicare Nursing Homes Residents, Daniela C. Moga, Qishan Wu, Pratik Doshi, Amie J. Goodin

Pharmacy Practice and Science Faculty Publications

Background: To examine factors predicting type of bladder antimuscarinics (BAM) initiated in nursing home (NH) residents.

Methods: Incident BAM initiators following NH admission were identified by constructing a retrospective cohort from Medicare files and Minimum Data Set (MDS). Participants included all residents 65 years and older admitted in Medicare-certified NH between January 1, 2007 and December 31, 2008 who were prescribed BAM and had continuous Medicare (Part A, B, and D) enrollment. Patient characteristics, medications, and comorbidities were derived from Medicare enrollment and claims. NH characteristics and health status were derived from MDS assessments. The outcome was defined as type …

Nuclear Spindles Pave The Way To Metastasis, Patrick J. Hensley, Natasha Kyprianou

Urology Faculty Publications

No abstract provided.

Tfpiα Interacts With Fva And Fxa To Inhibit Prothrombinase During The Initiation Of Coagulation, Jeremy P. Wood, Helle H. Petersen, Bingke Yu, Xiaoai Wu, Ida Hilden, Alan E. Mast

Gill Heart & Vascular Institute Faculty Publications

Tissue factor pathway inhibitor α (TFPIα) inhibits prothrombinase, the thrombin-generating complex of factor Xa (FXa) and factor Va (FVa), during the initiation of coagulation. This inhibition requires binding of a conserved basic region within TFPIα to a conserved acidic region in FXa-activated and platelet-released FVa. In this study, the contribution of interactions between TFPIα and the FXa active site and FVa heavy chain to prothrombinase inhibition were examined to further define the inhibitory biochemistry. Removal of FXa active site binding by mutation or by deletion of the second Kunitz domain (K2) of TFPIα produced 17- or 34-fold weaker prothrombinase inhibition, …

Cdc Grand Rounds: National Amyotrophic Lateral Sclerosis (Als) Registry Impact, Challenges, And Future Directions, Paul Mehta, D. Kevin Horton, Edward J. Kasarskis, Ed Tessaro, M. Shira Eisenberg, Susan Laird, John Iskander

Neurology Faculty Publications

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease, is a rapidly progressive fatal neurologic disease. Currently, there is no cure for ALS and the available treatments only extend life by an average of a few months. The majority of ALS patients die within 2–5 years of diagnosis, though survival time varies depending on disease progression (1,2). For approximately 10% of patients, ALS is familial, meaning it and has a genetic component; the remaining 90% have sporadic ALS, where etiology is unknown, but might be linked to environmental factors such as chemical exposures (e.g., heavy …

Development And Validation Of Nomograms Predictive Of Overall And Progression-Free Survival In Patients With Oropharyngeal Cancer, Carol Fakhry, Qiang Zhang, Phuc Felix Nguyen-Tân, David I. Rosenthal, Randal S. Weber, Louise Lambert, Andy M. Trotti Iii, William L. Barrett, Wade L. Thorstad, Christopher U. Jones, Sue S. Yom, Stuart J. Wong, John A. Ridge, Shyam S. D. Rao, James A. Bonner, Eric Vigneault, David Raben, Mahesh R. Kudrimoti, Jonathan Harris, Quynh-Thu Le, Maura L. Gillison

Radiation Medicine Faculty Publications

Purpose

Treatment of oropharyngeal squamous cell carcinoma (OPSCC) is evolving toward risk-based modification of therapeutic intensity, which requires patient-specific estimates of overall survival (OS) and progression-free survival (PFS).

Methods

To develop and validate nomograms for OS and PFS, we used a derivation cohort of 493 patients with OPSCC with known p16 tumor status (surrogate of human papillomavirus) and cigarette smoking history (pack-years) randomly assigned to clinical trials using platinum-based chemoradiotherapy (NRG Oncology Radiation Therapy Oncology Group [RTOG] 0129 and 0522). Nomograms were created from Cox models and internally validated by use of bootstrap and cross-validation. Model discrimination was measured by …