Medicine and Health Sciences Commons^™

Effects Of Off-Label Prescribing On Patient Decision Making, Douglas Paul

Electronic Theses and Dissertations

Objectives: Despite the comuse of off-label prescribing in the US, no research has been conducted to understand the impact of off-label prescribing on patient decision making. This study sought to measure the impact on trust in physicians, intentions of involvement in the decision making, beliefs about the drug, and initial compliance intentions in elderly and nonelderly populations. Methods. This study was designed to assess the effects of off-label prescribing using a 2 × 2 × 2 design. Using an online panel, 830 consumers were surveyed, 409 elderly and 421 nonelderly, using 8 different scenarios based on disease criticality, off-label use …

Functional Studies Of Novel Bioactives From Complex Host-Microbiomes As Drug Leads For Cancer, Infectious Disease, Depression And Pain, John Jason Bowling

Electronic Theses and Dissertations

The drug discovery process has become increasingly complex in comparison to early efforts particularly those involving diseases or conditions that affect large numbers of the human population. It is difficult to point directly to one factor leading evolution of the process but the definition of a mechanism of pharmacological action for a drug lead has noticeably become a higher priority. This evolution has helped diminish the stigma of natural products and compound supply issues. The issue of compound supply has also been addressed to some extent with the emergence of recombinant technologies and new synthetic methodology. With approximately 60 years …

The Effects Of A Multi-Component Wellness Program On Employee Biometrics, Jennifer Erin Patrick

Electronic Theses and Dissertations

Corporate wellness initiatives are gaining momentum as a critical indicator of business performance. Metabolic Syndrome is commonly used within corporations to assess the health of their employees and estimate potential healthcare costs. Using five risk factors (blood pressure, high density lipoprotein (HDL-C), triglycerides (TG), fasting blood glucose, and waist circumference) individuals with three or more risk factors are classified as having Metabolic Syndrome. Voluntary pre and post health screenings were conducted at a rural manufacturing plant. A multi-component wellness program was conducted over six months to determine if the program would have significant beneficial effects on employee biometrics and Metabolic …

An Evaluation Of Medicaid Programs Using Medication Use-Related Quality Measures, Vennela Thumula

Electronic Theses and Dissertations

Objective: To assess quality of care provided to Medicaid beneficiaries using medication use-related quality indicators. Methods: This study is a retrospective analysis of 2006 & 2007 Medicaid administrative claims data from 45 states and DC. Eleven medication use-related measures (adherence/persistence and standard of care) from the AHRQ initial core set were included. A composite measure of medication use-related quality was also created. Patient case-mix adjusted measure scores were computed using hierarchical logistic regression models. States were ranked on both case-mix adjusted and unadjusted scores and categorized into top (?20%), medium (60%) and bottom (?20%) performers. Agreement in rankings and groups …

The Effect Of Exercise On Mechanical Pressure Pain Threshold In The Presence And Absence Of Delayed-Onset Muscle Soreness, Brandon Tynes

Electronic Theses and Dissertations

Research has shown decreased pain sensitivity (hypoalgesia) during and following maximal and sub-maximal isometric exercise (Koltyn, 2002). Research on fibromyalgia patients however has shown the same exercises increase pain sensitivity (hyperalgesia) (Staud, Robinson, & Price, 2005; Kosek, Ekholm, & Hansson, 1996). The purpose of the present study was to examine the effects of exercise on pressure pain thresholds (PPT) in the presence and absence of delayed-onset muscle soreness (DOMS) within the ipsilateral (contracting) and contralateral quadriceps muscle and plurisegmental finger. Data were collected using twenty-five male participants (aged 18-29) over five testing days: two days of familiarization, one day of …

Isolation, Structure Elucidation And Biological Evaluation Of Natural Products From Plants And Fungi, Xiaoning Wang

Electronic Theses and Dissertations

Natural products have provided considerable value for drug discovery over the past half-century. Nearly four fifth of drugs were natural products or inspired by natural compounds. Bioactive secondary metabolites isolated from natural source, either fungal or terrestrial, are relatively safer for human health and the environment and can serve as drug or as drug leads for the development of synthetic or semi-synthetic analogs. Natural products have also been successfully used in agriculture as plant growth regulators, signal transductions, fungicides, herbicides and tranquilizers. In our continued efforts to identify bioactive compounds, seventy-seven plant and fungal extracts were evaluated using a direct-bioautography …

Antileishmania Compounds From An Unidentified Endophytic Fungus And Biotransformation Of 5,7,2`,4`,5`-Pentahydroxyflavonol, Ahmed Idris

Electronic Theses and Dissertations

Leishmaniasis is a parasitic disease remaining a major public health problem. It causes illness and death especially in developing countries. Comchemotherapeutic agents currently used are often inadequate, requiring long courses of parenteral administration, having toxic side effects or becoming less effective due to the emergence of resistant strains. Thus, there is an urgent need for new, effective, and inexpensive drugs. In the fight against leishmaniasis, natural products are important sources of novel therapeutic agents. The goal of our research is to study secondary metabolites from endophytic fungi as a source of effective antileishmanial agents. Many crude extracts from endophytic fungi …

Dynamic Informed Consent Processes Vital For Treatment With Antidepressants, Abilash A. Gopal, Lisa Cosgrove, Itay Shuv-Ami, Emily E. Wheeler, Melissa J. Yerganian, Harold J. Bursztajn

Counseling, School Psychology & Sport Faculty Publication Series

Advances in technology and transparency have greatly accelerated the ability of clinicians to remain current with regards to being informed and informing patients about the risk/benefit ratio when considering antidepressant medication. In spite of this, the current climate of pharmaceutical industry influence on medical practice does much to hinder informed consent processes. Recent findings of previously unknown and potentially dangerous adverse effects of the second- and third-generation classes of antidepressants underscore the importance of enhancing the practice of informed consent. After considering the concept of informed consent as it has evolved over time, the authors summarize some of the newer …

Discovery Of Novel Glycogen Synthase Kinase-3beta Inhibitors: Molecular Modeling, Virtual Screening, And Biological Evaluation, Gang Fu

Electronic Theses and Dissertations

Glycogen synthase kinase-3 (GSK-3) is a multifunctional serine/threonine protein kinase which is engaged in a variety of signaling pathways, regulating a wide range of cellular processes. Due to its distinct regulation mechanism and unique substrate specificity in the molecular pathogenesis of human diseases, GSK-3 is one of the most attractive therapeutic targets for the unmet treatment of pathologies, including type-II diabetes, cancers, inflammation, and neurodegenerative disease. Recent advances in drug discovery targeting GSK-3 involved extensive computational modeling techniques. Both ligand/structure-based approaches have been well explored to design ATP-competitive inhibitors. Molecular modeling plus dynamics simulations can provide insight into the protein-substrate …

Geographic And Host-Microbe Symbiotic Influence On Secondary Metabolism, Samuel Hamed Abbas

Electronic Theses and Dissertations

This thesis is composed of studies that regard the advancement to the Arctic region and the importance of host-microbe interactions in natural product discovery. Bioactive metabolites have been reported from a myriad of marine and terrestrial organisms around the world including plants, insects, sponges, tunicates, bacteria, and fungi among others. Many macroorganisms, of which the metabolites are found, depend on the symbiotic relationship of microorganisms for metabolite production. The scope of this work is to investigate secondary metabolism of both marine and terrestrial organisms from different areas of the world as well as search for the importance of host-microbe symbiosis …

Development And Comparative Predictive Validity Of An Outpatient Medication Exposure Measure For Risk Adjustment Using Retrospective Claims Data, Kyle Dennis Null

Electronic Theses and Dissertations

The purpose of this study was to develop and test a measure of outpatient prescription utilization (medication exposure measure, or MEM) that may be coupled with the CMS-HCC and CMS-RxHCC methodologies to improve risk-adjusted payments to Medicare Part C and Part D plans. Studies have identified prescription measures that predict future expenditures; however, many are easily manipulable by health plans or practitioners, thus limiting their utility as risk-adjusters. The addition of a non-manipulable prescription utilization measure to existing risk-adjustment models may improve prediction, reducing adverse risk selection incentives by health plans. A secondary objective of this study was to evaluate …

Student Success Tracking Pilot Program, Jane M. Souza, Richard O'Brocta

Pharmacy Faculty/Staff Publications

Objective: The purpose of study is to pilot a program in which all P1 students input their exam grades for each course in the fall semester into E*Value. Alongside their grades they record reflections on their performance. This information, visible only to the individual students and their advisors, is used to promote meaningful dialog during advising sessions.

Method: A form was created in E*Value for students to input their exam grades and reflections on those grades. Faculty advisors were asked to use this data during advising sessions. Feedback was collected through Qualtrics surveys for faculty and students as well as …

Cilostazol Prevents Endothelin-Induced Smooth Muscle Constriction And Proliferation, Yoshifumi Kawanabe, Maki Takahashi, Xingjian Jin, Shakila Abdul-Majeed, Andromeda M. Nauli, Youssef Sari, Surya M. Nauli

Pharmacy Faculty Articles and Research

Cilostazol is a phosphodiesterase inhibitor that has been shown to inhibit platelet activation. Endothelin is known to be the most potent endogenous growth promoting and vasoactive peptide. In patients and animal models with stroke, the level of circulating endothelin increases and complicates the recovery progress contributed by vascular constriction (an immediate pathology) and vascular proliferation (a long-term pathology). However, the effects of cilostazol on endothelin have not been explored. To demonstrate the dual-antagonizing effects of cilostazol on vasoconstriction and cell proliferation induced by endothelin, we used primary culture of mouse vascular smooth muscle cells in vitro, mouse femoral artery ex …

Confounding Issues In Estimation Of Patient-Specific Pharmacokinetic Parameters And Dosage Individualization Of Aminoglycosides, Reza Mehvar

Pharmacy Faculty Articles and Research

Aminoglycoside antibiotics are usually administered by multiple short intravenous infusions at fixed intervals. Today, equations reported 35 years ago by Sawchuk and Zaske are still the cornerstone of methods used for determination of patient-specific pharmacokinetic parameters of aminoglycosides and individualization of drug dosage regimens in many clinical settings. Additionally, these methods are included in many clinical pharmacology curricula in pharmacy and other related fields. However, there are a few issues with regard to the application and/or modification of this method in clinical settings, which may result in some confusion among novice clinicians. For example, serum samples collected from different intervals …

What Evidence Is Available On Apixaban For The Primary Prevention Of Stroke In Patients With Atrial Fibrillation?, Justin Dang, Laura Tsu

Pharmacy Faculty Articles and Research

This drug information question and answer sheet discusses the use of apixaban (Eliquis) for the primary prevention of stroke in patients with atrial fibrillation.

Anti-Platelet Therapy In Acute Coronary Syndromes: Updates In Therapy After Stent Implantation, Ryan Mckenzie, Andrew Park, Laura Tsu

Pharmacy Faculty Articles and Research

This home-study CPE activity has been developed to educate pharmacists on updates in anti-platelet therapy after stent implantation.

The Importance Of Active Learning And Practice On The Students' Mastery Of Pharmacokinetic Calculations For The Intermittent Intravenous Infusion Dosing Of Antibiotics, Reza Mehvar

Pharmacy Faculty Articles and Research

Estimation of pharmacokinetic parameters after intermittent intravenous infusion (III) of antibiotics, such as aminoglycosides or vancomycin, has traditionally been a difficult subject for students in clinical pharmacology or pharmacokinetic courses. Additionally, samples taken at different intervals during repeated dose therapy require manipulation of sampling times before accurate calculation of the patient-specific pharmacokinetic parameters. The main goal of this study was to evaluate the effectiveness of active learning tools and practice opportunities on the ability of students to estimate pharmacokinetic parameters from the plasma samples obtained at different intervals following intermittent intravenous infusion.

Choreographing The Adenylyl Cyclase Signalosome: Sorting Out The Partners And The Steps, Rennolds S. Ostrom, Amy S. Bogard, Robert Gros

Pharmacy Faculty Articles and Research

Adenylyl cyclases are a ubiquitous family of enzymes and are critical regulators of metabolic and cardiovascular function. Multiple isoforms of the enzyme are expressed in a range of tissues. However, for many processes, the adenylyl cyclase isoforms have been thought of as essentially interchangeable, with their impact more dependent on their common actions to increase intracellular cyclic adenosine monophosphate content regardless of the isoform involved. It has long been appreciated that each subfamily of isoforms demonstrate a specific pattern of “upstream” regulation, i.e., specific patterns of ion dependence (e.g., calcium-dependence) and specific patterns of regulation by kinases (protein kinase A …

Kshv Infection Of Endothelial Cells Manipulates Cxcr7-Mediated Signaling: Implications For Kaposi’S Sarcoma Progression And Intervention, Jennifer Totonchy, Lisa Clepper, Janet Douglas, Liron Pantanowitz, Klaus Fruh, Ashlee V. Moses

Pharmacy Faculty Articles and Research

"CXCR7 was recently characterized as an alternative receptor for the chemokine CXCL12/SDF-1, previously thought to bind and signal exclusively through CXCR4.We recently identified CXCR7 as a key cellular factor in the endothelial cell (EC) dysfunction associated with KSHV infection. CXCL12 signaling is critically associated with tumor growth, angiogenesis and metastasis in several diverse tumors and is one of the most studied chemokine/chemokine receptor interactions in cancer systems. The tumorigenic activity of the CXCL12 signaling axis offers an attractive target for therapeutic intervention in multiple cancers including Kaposi’s Sarcoma (KS). However, most of the research to date was based on the …

Structural Properties Of Thermoresponsive Poly(N-Isopropylacrylamide)-Poly(Ethyleneglycol) Microgels, J. Clara-Rahola, A. Fernandez-Nieves, B. Sierra-Martin, A. B. South, L. Andrew Lyon, J. Kohlbrecher, A. F. Barbero

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The application of RNA interference to treat disease is an important yet challenging concept in modern medicine. In particular, small interfering RNA (siRNA) have shown tremendous promise in the treatment of cancer. However, siRNA show poor pharmacological properties, which presents a major hurdle for effective disease treatment especially through intravenous delivery routes. In response to these shortcomings, a variety of nanoparticle carriers have emerged, which are designed to encapsulate, protect, and transport siRNA into diseased cells. To be effective as carrier vehicles, nanoparticles must overcome a series of biological hurdles throughout the course of delivery. As a result, one promising …

Mechanism Of Action Of A Novel Antifungal Compound, Amber Ward

Honors Theses

Opportunistic fungal infections have become problematic in recent years. There has been an emergence of new fungal pathogens, development of antifungal resistance, and increasing prevalence. In addition, toxicity, resistance, and lack of efficacy as a single agent limit the effectiveness of current antifungal drugs. Therefore, new drugs targeting new pathways are greatly needed. An analog derived from the marine natural product phloeodictine, analog PHL5-34A, was identified as having strong in vitro antifungal activity. In this study, its mechanism of action (MOA) was investigated in the model yeast, Saccharomyces cerevisiae. This study made use of a collection of 166 yeast mutants …

Hepatic Immunosuppressive Effects Of Systemically- Administered Novel Dextran-Methylprednisolone Prodrugs With Peptide Linkers In Rats, Imam H. Shaik, Hitesh K. Agarwal, Keykavous Parang, Reza Mehvar

Pharmacy Faculty Articles and Research

The hepatic immunosuppressive activities of two novel dextran prodrugs of methylprednisolone (MP) containing one (DMP1) or five (DMP5) amino acids as linkers were studied in rats. At various times (02 weeks) after intravenous administration of single 5 mg/kg (MP equivalent) doses of each prodrug or MP succinate (MPS), livers were isolated and immunologically stimulated ex vivo with lipopolysaccharide. The concentrations of tumor necrosis factor (TNF)-a in the outlet perfusate were then quantitated to assess immune response. Additionally, the concentrations of DMP1, DMP5, and/or MP were measured in the liver. MPS, DMP5, or DMP1 injections caused a maximum of 48.9%, 63.5%, …

A Survey Of Top 200 Drugs—Inconsistent Practice Of Drug Strength Expression For Drugs Containing Salt Forms, Daniel Prohotsky, Fang Zhao

Doctoral External Publications

Many ionizable drugs are developed and marketed as salt forms. However, there are no clear US regulatory guidelines on drug strength labeling for salts. The strengths of some drugs are expressed as salts and some as free acids/bases. This study surveyed the top 200 US drugs to assess the common practice in industry. The top 200 drugs prescribed in the United States were included in this survey. The drugs containing active pharmaceutical ingredient (API) salts were selected for analysis. Generic or combination products with redundant API salts were excluded. The package insert of each selected drug was reviewed, and the …

Chronic Opioid Use In Fibromyalgia Syndrome: Characteristics And Outcomes, Jacob T. Painter

Theses and Dissertations--Pharmacy

Fibromyalgia syndrome (FMS) is a chronic pain condition with significant societal and personal burdens of illness. Chronic opioid therapy in the treatment of chronic nonmalignant pain has increased drastically over the past decade. This is a worrisome trend in general, but specifically, given the pathophysiologic characteristics seen in fibromyalgia syndrome patients, the use of this class of medication deserves special scrutiny. Although the theoretical case against this therapy choice is strong, little empirical evidence exists. In order to supplement this literature, retrospective analysis methods are utilized to examine the association of state-, provider-, and patient level characteristics with the prevalence …

Discovery Of Gz-793a, A Novel Vmat2 Inhibitor And Potential Pharmacotherapy For Methamphetamine Abuse, David B. Horton

Theses and Dissertations--Pharmacy

Methamphetamine abuse is a serious public health concern affecting millions of people worldwide, and there are currently no viable pharmacotherapies to treat methamphetamine abuse. Methamphetamine increases extracellular dopamine (DA) concentrations through an interaction with the DA transporter (DAT) and the vesicular monoamine transporter-2 (VMAT2), leading to reward and abuse. While numerous studies have focused on DAT as a target for the discovery of pharmacotherapies to treat psychostimulant abuse, these efforts have been met with limited success. Taking into account the fact that methamphetamine interacts with VMAT2 to increase DA extracellular concentrations; the focus of the current work was to develop …

Molecular Mechanisms Of Thromboxane A2 Receptor-Mediated Invasion In Lung Cancer Cells, Xiuling Li

Theses and Dissertations--Pharmacy

Thromboxane A2 receptor (TP) has been shown to play important roles in multiple aspects of cancer development including regulation of tumor growth, survival and metastasis. Molecular mechanisms of TP mediated cancer cell invasion remain to be identified. TP agonist, I-BOP, significantly elevated several matrix metalloproteinases (MMPs) including MMP-1, MMP-3, MMP-9 and MMP-10 in A549 human lung adenocarcinoma cells overexpressing TPα (A549-TPα) or TPβ (A549-TPβ). Signaling pathways of I-BOP-induced MMP-1 expression were examined in further detail as a model system for MMPs induction. Signaling molecules involved in I-BOP-induced MMP-1 expression were identified by using specific inhibitors including small interfering (si)-RNAs of …

Localization And Functional Characterization Of Oatp4c1 Transporter In In Vitro Cell Systems And Human/Rat Tissues, Kuei-Ling Kuo

Theses and Dissertations--Pharmacy

The organic anion transporting polypeptide 4c1 (Oatp4c1) was previously identified as a novel uptake transporter predominantly expressed at the basolateral membrane in the rat kidney proximal tubules. Its functional role was suggested to be a vectorial transport partner of an apically-expressed efflux transporter for the efficient translocation of physiological substrates into urine, some of which were suggested to be uremic toxins. In vitro studies in polarized cell lines showed that upon transfection rat Oatp4c1 localizes at the apical membrane. The objectives of this project were to further validate the subcellular localization of Oatp4c1/OATP4C1 in rat and human tissues as well …

Influence Of Oncotype Dx® On Chemotherapy Prescribing In Early Stage Breast Cancer Patients: A Claims-Based Evaluation Of Utilization In The Real World, Kenneth Neil Kennedy

Theses and Dissertations--Pharmacy

The decision for adjuvant therapy in women with early stage breast cancer (ESBC) has historically been guided by the presence or absence of specific biological markers (hormone and HER2 receptors), age, and extent of nodal involvement. Oncotype DX® is a validated assay that quantifies protein expression that can predict the risk of cancer recurrence. This study evaluates if the use of Oncotype DX® impacts chemotherapy prescribing in ESBC. This retrospective, cohort study identified patients with ESBC from a large commercially insured population from January 2007 through June 2009. Patients were identified as having ESBC by utilizing procedure and diagnosis codes …

Role Of Alternative Macrophage Activation In Mediating Fibrosis In Pseudomonas Aeruginosa Pneumonia, Susan Elizabeth Birket

Theses and Dissertations--Pharmacy

Patients with cystic fibrosis who are infected with the pathogen Pseudomonas aeruginosa have shown favorable responses to the drug azithromycin (AZM). This drug works in an anti-inflammatory capacity, improving clinical outcomes and improving quality of life in this population. The drug has also been shown to affect macrophage polarization by shifting these cells away from an inflammatory phenotype toward an alternatively activated anti-inflammatory phenotype. The full impact of this phenotypic change is not well understood in the context of the response to P. aeruginosa infection, or the overall immune response in cystic fibrosis.

To understand how the AZM-polarized macrophage affects …

Nanocrystals Of Chemotherapeutic Agents For Cancer Theranostics: Development And In Vitro And In Vivo Evaluation, Christin P. Hollis

Theses and Dissertations--Pharmacy

The majority of pharmacologically active chemotherapeutics are poorly water soluble. Solubilization enhancement by the utilization of organic solvents often leads to adverse side effects. Nanoparticle-based cancer therapy, which is passively targeted to the tumor tissue via the enhanced permeation and retention effect, has been vastly developed in recent years. Nanocrystals, which exist as crystalline and carry nearly 100% drug loading, has been explored for delivering antineoplastic agents. Additionally, the hybrid nanocrystal concept offers a novel and simple way to integrate imaging agents into the drug crystals, enabling the achievement of theranostics. The overall objective of this dissertation is to formulate …