Medicine and Health Sciences Commons^™

Housing Status, Patient Characteristics, And Ed Utilization Associated With Medication Prescribing At Ed Discharge Among Homeless And Nonhomeless Adults In Urban Hospitals In The United States, Lauren Cox

Theses and Dissertations

This cross-sectional study used a weighted sample of ED visits contained in the 2010-2015 years of the National Hospital Ambulatory Care Survey-Emergency Department (NHAMCS-ED) dataset. The purpose of this study was to: 1) identify differences in predisposing, enabling, and need characteristics, and ED use and medication prescribing characteristics between homeless and nonhomeless ED users; 2) assess the association between housing status and medication prescribing at ED discharge, and identify variables contributing to the disparity in medication prescribing between homeless and nonhomeless ED users; and 3) assess the predisposing, enabling, need, and ED use characteristics that predict medication prescribing at ED …

Effects Of Hiv-1 Tat And Drugs Of Abuse On Antiretroviral Penetration Inside Different Cns Cell Types, Sulay H. Patel

Theses and Dissertations

Human immunodeficiency (HIV) infection can result in neurocognitive deficits in about one-half of infected individuals. Despite excellent systemic effectiveness, restricted antiretroviral penetration across the blood-brain barrier (BBB) is a major limitation in fighting HIV infection within the central nervous system (CNS). Drug abuse exacerbates cognitive impairment and pathologic CNS changes in HIV-infected individuals. This work investigates the effects of the HIV-1 protein, Tat, and drugs of abuse on factors affecting drug penetration into the brain.

Firstly, an in vitro model of the blood-brain barrier was built to study effects of HIV-1 Tat and methamphetamine (Meth) on integrity and function of …

Economic Burden Of Renal Cell Carcinoma (Rcc) And Treatment Patterns, Overall Survival And Healthcare Costs Among Older Metastatic Rcc Patients, Hrishikesh P. Kale

Theses and Dissertations

Background

Renal cell carcinoma (RCC) is the most common type of kidney cancer. Patients diagnosed with metastatic RCC (mRCC) have shorter overall survival compared to those diagnosed at earlier stages. Several targeted therapies, which cost from $7,000 - $16,000 per month have been approved since 2005 to treat mRCC. In addition, there is a growing interest in the use of cytoreductive nephrectomy (CN) with targeted therapies among mRCC patients. However, little is known regarding the economic burden of RCC and role of CN and prescribing patterns of targeted therapies among older mRCC patients.

Objectives

1) To assess the economic burden …

Glycosaminoglycan Lyases In The Preparation Of Oligosaccharides, Alhumaidi B. Alabbas

Theses and Dissertations

Glycosaminoglycans are heterogeneous polysaccharides that mediate important biological functions. There has been considerable interest in deciphering the precise GAG sequences that are responsible for protein interactions. In fact, several GAG oligosaccharides have been discovered to date as targeting proteins with higher level of specificity. Yet, it has been difficult to develop GAG oligosaccharides as drugs. One of the key reasons for this state of art is that GAG synthesis is extremely challenging and is highly structure-specific. Thus, much of the biology and pharmacology of GAG remains unknown and unexploited to date.

An alternative approach is to prepare GAG oligosaccharides using …

Development Of Small Molecule Neuroprotectants, Ashley Boice

Theses and Dissertations

Neurodegenerative diseases are a class of conditions that lead to progressive atrophy of different parts of the central nervous system (CNS). These diseases lead to devastating clinical outcomes to patients and give rise to an enormous socio-economical burden on society.¹ One commonality among some of the most well-known neurodegenerative disorders, e.g. Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS), is neuroinflammation.^2-4 Neuroinflammation stems from interactions of the innate immune system with toxins and insults to the central nervous system. In the case of irremovable or chronic insults and toxins, this leads to chronic damaging …

Elucidation Of Substrate Binding Interactions For Human Organic Cation Transporters 1 (Slc22a1) And 2 (Slc22a2) Using In Silico Homology Modeling In Conjunction With In Vitro Site-Directed Mutagenesis And Kinetic Analysis, Raymond E. Lai

Theses and Dissertations

The organic cation transporters (OCTs) play a critical role in the absorption, distribution and elimination of many drugs, hormones, herbal medicines, and environmental toxins. Given the broad substrate specificity of OCTs, they fall victim to the high susceptibility for contributing to harmful drug-drug interactions. Further defining how human (h)OCTs mechanistically bind to its broad array of substrates will provide significant insight to the understanding and prediction of drug-drug interactions in polypharmacy patients and the advancement of future rational drug design for therapeutics targeting OCTs. The goal of the current study was to elucidate the critical amino acid residues for transporter-substrate …

Rational Design Of Allosteric Modulators Of Hemoglobin As Dual Acting Antisickling Agents, Piyusha P. Pagare

Theses and Dissertations

Intracellular polymerization of deoxygenated sickle hemoglobin (Hb S) remains the principal cause of the pathophysiology associated with sickle cell disease (SCD). Naturally occurring and synthetic allosteric effectors of hemoglobin (AEH) have been investigated as potential therapeutic agents for the treatment of SCD. Several aromatic aldehydes, including vanillin, have been studied previously as AEHs for their antisickling activities. Specifically, these compounds form Schiff- base adduct with Hb to stabilize the oxygenated (R) state, increase Hb affinity for O2 and concomitantly prevent the hypoxia-induced primary pathophysiology of Hb S polymerization and RBC sickling, in turn, ameliorating several of the cascading secondary adverse …

Galantamine's Deconstruction In The Quest Of A Pam Pharmacophore, Malaika Argade

Theses and Dissertations

Alzheimer’s disease is a progressive neurodegenerative disorder generally affecting people above the age of 65 years. Even though the pathophysiological hallmarks of AD were established more than a hundred years ago, there is yet to be a drug that can stop its characteristic neuronal damage. Of the five currently FDA-approved drugs, galantamine has a unique mechanism of action. Apart from being an AChE inhibitor, galantamine can effectively potentiate (positive allosteric modulator) the effect of agonists at nAChRs at concentrations lower than those required for its action as an AChE inhibitor. Perhaps the clinical benefits observed with galantamine are associated mainly …

Development And Validation Of A Semi-Physiological Pharmacokinetic (Pbpk) Model To Predict Systemic And Pulmonary Exposures After Intravenous, Oral Administration And Pulmonary Inhalation Of Selected Drugs, Budesonide, Tobramycin And Ciprofloxacin, In Humans, Bishoy Hanna

Theses and Dissertations

Using a semi-PBPK modeling/quantitative meta-analysis approach, this project investigated what factors affect pulmonary and systemic exposures of Budesonide (BUD), Tobramycin (TOB), and Ciprofloxacin (CIP) after inhalation:

Three structurally different pulmonary disposition models were developed for each drug, including pulmonary absorption (all three), excretion (TOB and CIP) and sequestration (TOB) in a peripheral and central lung compartment. Systemic disposition parameters were estimated using available human mean plasma (c_p(t)) and sputum (c_s(t)) concentration profiles after IV administration, and GI absorption parameters were estimated from these profiles after oral administration. Pulmonary disposition parameters were estimated from c_p(t) …

Prescription Drug Monitoring Programs And Opioid Poisoning: Evaluating The Impact Of Prescriber Use Mandates On Prescription Opioid Poisoning Emergency Department Visits, Sarah Almanie

Theses and Dissertations

Introduction: Prescription drug monitoring programs (PDMPs) are one strategy established to curb the prescription opioid abuse epidemic. Prescriber use mandates has emerged as a promising practice to increase PDMPs impact on prescription opioid abuse; however, evidence of its effectiveness has not yet been established. Kentucky was the first state to implement comprehensive prescriber use mandates in July 2012.

Objective: To assess the relationship between prescriber use mandates policy and emergency department (ED) visits related to prescription opioid poisoning among adults in Kentucky and

North Carolina. Secondary aim: to evaluate the economic impact of prescriber use mandates in Kentucky.

Methods: A …

Association Between Warfarin Adherence Trajectories, Hospitalization Risk, And Healthcare Utilization Among Medicare Patients With Atrial Fibrillation: A Group-Based Trajectory Modelling Approach, Mai Alhazami

Theses and Dissertations

Introduction: Warfarin is the most commonly prescribed drug for stroke prevention among Atrial Fibrillation (AF) patients, especially in older adult populations, but medication nonadherence reduces its effectiveness in clinical practice. Group Based Trajectory Models (GBTM) have been used to identify distinct patterns of adherence behavior related to various medications and understand the patient characteristics associated with each trajectory. The objectives of the study were: 1) Describe trajectories of warfarin adherence among Medicare AF patients, 2) Assess impact of adherence trajectories on AF-related hospitalization, 3) Estimate the AF-related direct costs for each adherence trajectory group.

Methods: We identified elderly AF patients …

Mass Spectrometry-Based Proteomics Analysis Of Secreted Proteins, Emmanuel K. Cudjoe Jr

Theses and Dissertations

Secreted proteins play important roles in many cellular functions and molecular processes. Because secreted proteins potentially enter the blood stream, they can serve as valuable measures of health and disease useful for disease diagnosis and prognosis, therapeutic target identification, and patient stratification in personalized medicine. Consequently, significant interest exists in secreted protein analysis within complex biospecimens, particularly blood but significant bioanalytical challenges including the wide protein dynamic range >10 orders of magnitude remain. The cellular secretome therefore represents a viable alternative to direct biomarker discovery in biofluids. Finally, cellular systems are amenable to labeling for the production of intact stable …

Aerosolized Surfactants: Formulation Development And Evaluation Of Aerosol Drug Delivery To The Lungs Of Infants, Susan Boc

Theses and Dissertations

The overall aim of this research project was to develop surfactant dry powder formulations and devices for efficient delivery of aerosol formulations to infants using the excipient enhanced growth (EEG) approach. Use of novel formulations and inline delivery devices would allow for more efficient treatment of infants suffering from neonatal respiratory distress syndrome and bronchiolitis.

A dry powder aerosol formulation has been developed using the commercial product, Survanta ® (beractant) and EEG technology to produce micrometer-sized hygroscopic particles. Spray drying and formulation parameters were initially determined with dipalmitoylphosphatidylcholine (DPPC, the dominant phospholipid in pulmonary surfactant), which produced primary particles 1 …