Medicine and Health Sciences Commons^™

Evaluation Of Medication Risks For Falls On An Inpatient Medical/Surgical Unit, Joseph Zegar

Undergraduate Honors Thesis Collection

Purpose: Patient falls during hospitalization can delay discharge and decrease quality of life. Medications are one factor that can impact fall risk. This study examines patients who fell while admitted to a cardiac surgery unit to identify which high-risk medications are most prevalent to promote patient safety.

Methods: This was a retrospective case control study. Adult patients over the age of 18 were included. Exclusion criteria included pediatric patients and those with an intentional fall event. A total of 39 falls and 78 controls were analyzed in the study. The primary outcome was a fall event during hospitalization. Other variables …

Determining The Role Played By Aryl Hydrocarbon Receptor (Ahr) In The Colon Carcinoma Tumor Model, Poonam Yakkundi

University of the Pacific Theses and Dissertations

Aryl hydrocarbon receptor (AHR), commonly known as an environmental sensor involved in the metabolism and elimination of xenobiotic substances, is also an important modulator in the development and functioning of the immune system. AHR expression is varied in the T cell subsets with the highest expression in T-helper 17 and T regulatory cells. Work from many researchers has suggested that AHR can act as a tumor promoter or a tumor suppressor depending on the tumor type. Our goal is to understand the role played by AHR in MC38 syngeneic colon carcinoma tumor model. In the absence of AHR, MC38 tumor …

Influence Of The Estrous Cycle And Female Sex Hormones On Ghb Toxicokinetics, Hao Wei

University of the Pacific Theses and Dissertations

Gamma-Hydroxybutyrate (GHB) is an endogenous short-chain fatty acid formed from Gamma-aminobutyric acid (GABA). Clinically, GHB is marketed in the United States as Xyrem to treat narcolepsy with cataplexy and in Europe for the treatment of alcohol withdrawal and narcolepsy. However, the illicit use and abuse of GHB occurs due to its sedative/hypnotic and euphoric effects. Monocarboxylate transporters (MCTs and SMCTs) are integral membrane proteins that control the bidirectional transport of endogenous substrates including lactate, acetate and pyruvate. They have also been found to transport and mediate the clearance and distribution of GHB. MCTs demonstrate a wide tissue distribution, including brain, …

A Comprehensive Examination Of The Pharmacist's Role In Mental Illness, Kaleb D. Barnes

Honors Theses

The number of people receiving mental illness diagnoses has increased in the last two decades. As one of the most accessible healthcare professionals, pharmacists need to be prepared to assist in the management of patients with mental illness. In this study, the objective was to see how pharmacists' mental illness knowledge, acceptable social distance, familiarity, and perceived barriers may predict pharmacists' attitude toward patients with mental illness and also their willingness to provide care to patients with mental illness. The secondary objectives of this study were to test for differences in knowledge, attitude, perceived barriers, and willingness to provide care …

An Evaluation Of Mobile Apps For The Collation Of Materials To Propose An App For Type-2 Diabetes Self-Management, Sydney Watson

Honors Theses

This study is an evaluation of mobile application (apps) with the intention to collate materials appropriate for the proposal of a mobile app for type 2 diabetes self-management. In order to decipher the most vital aspects to be included in the app, an evaluation of mobile apps pertaining to nutrition and diabetes management were investigated. It was found that there is a lack of mobile apps that have all-encompassing features regarding the management of the disease. Future app developers looking to develop a mobile app that is efficient in type 2 diabetes self-management should include each feature as follows: blood …

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 …

เภสัชจลนศาสตร์ประชากรของยาแวนโคมัยซินในผู้ป่วยเด็กชาวไทย, ชนิกา ชูพันธ์

Chulalongkorn University Theses and Dissertations (Chula ETD)

การศึกษาแบบเก็บข้อมูลย้อนหลังนี้มีวัตถุประสงค์เพื่อสร้างแบบจำลองทางเภสัชจลนศาสตร์และหาปัจจัยที่มีผลต่อค่าพารามิเตอร์ทางเภสัชจลนศาสตร์ของยาแวนโคมัยซินในผู้ป่วยเด็กชาวไทย ค่าความเข้มข้นของ ยาแวนโคมัยซินในซีรั่มจานวน 348 ตัวอย่าง จากผู้ป่วยเด็กอายุระหว่าง 1 เดือน ถึง 18 ปี ที่เข้ารับการรักษา ณ โรงพยาบาลจุฬาลงกรณ์ สภากาชาดไทย ระหว่างปี พ.ศ. 2555-2560 จานวน 212 คน วิเคราะห์ข้อมูลเภสัช จลนศาสตร์ประชากรด้วยโปรแกรม NONMEM® โดยวิธี first-order conditional estimation with interaction ลักษณะทางเภสัชศาสตร์ของยาแวนโคมัยซินอธิบายได้ด้วยแบบจำลองชนิดหนึ่งห้องที่มีการกำจัดยา แบบปฏิกิริยาอันดับหนึ่ง ค่าเฉลี่ยอัตราการกำจัดยาแวนโคมัยซิน (CL) มีค่า 0.13 ลิตร/ชั่วโมง/กิโลกรัม และ ค่าเฉลี่ยปริมาตรการกระจายยา (Vd) มีค่า 0.88 ลิตร/กิโลกรัม ปัจจัยที่มีผลต่อค่าพารามิเตอร์ทางเภสัชศาสตร์ ได้แก่ น้ำหนัก (กิโลกรัม) และอัตราการกรองของไต (มิลลิลิตร/นาที/1.73 ตารางเมตร) ดังแสดงในสมการ CL (ลิตร/ชั่วโมง) = 1.66*(น้ำหนัก/14)[superscript 0.75]*(อัตราการกรองของไต/108.9) และ V (ลิตร) = 12.7*(น้ำหนัก/14) ค่า ความผันแปรระหว่างบุคคลของ CL เท่ากับร้อยละ 34.8 ค่าความผันแปรระหว่างบุคคลของ V เท่ากับร้อยละ 39.6 และแบบจำลองสุดท้ายถูกตรวจสอบความสมเหตุสมผลด้วยวิธี bootstrap และ visual predictive check (VPC) ค่าพารามิเตอร์จากแบบจำลองสุดท้ายมีค่าใกล้เคียงกับค่าพารามิเตอร์ที่ได้จากการทำ bootstrap 1,000 ครั้ง และอยู่ในช่วงความเชื่อมั่นที่ร้อยละ 95 ผลการจำลองข้อมูลด้วยวิธี VPC 1,000 ครั้ง พบค่าความเข้มข้นของ ยาแวนโคมัยซินร้อยละ 6 ที่อยู่นอกช่วงความเชื่อมั่นที่ร้อยละ 90 แสดงถึงความเหมาะสมของแบบจำลองดังกล่าว ในการอธิบายเภสัชจลนศาสตร์ของยาแวนโคมัยซิน

Development Of Novel Phenanthroline And Thiazole Orange Derived G-Quadruplex Ligands And Telomerase Inhibitors, Siwen Wang

University of the Pacific Theses and Dissertations

The end of the human chromosome is protected by telomeres which contain a special tandem guanine-rich DNA sequence, 5’-TTAGGG. The length of telomeres is shortened during cell replications, and its length limits the replication capacity of cells. Telomerase is over-expressed in 85–90% of cancer cells, responsible for extending the telomere length in cancer cells. Guanine-rich DNA sequence can self-assemble into unique G-quadruplex structures that interfere with the extension of telomeres by telomerase. Therefore, DNA G-quadruplex has recently received much attention because of its important regulatory functions in telomerase-mediated cancerization. The formation of G-quadruplex requires monovalent cations (Na+ and K+) or …

Scalable Feature Selection And Extraction With Applications In Kinase Polypharmacology, Derek Jones

Theses and Dissertations--Computer Science

In order to reduce the time associated with and the costs of drug discovery, machine learning is being used to automate much of the work in this process. However the size and complex nature of molecular data makes the application of machine learning especially challenging. Much work must go into the process of engineering features that are then used to train machine learning models, costing considerable amounts of time and requiring the knowledge of domain experts to be most effective. The purpose of this work is to demonstrate data driven approaches to perform the feature selection and extraction steps in …

Alpha-Glucosidase Inhibitors From Dendrobium Scabrilingue, Chalermporn Sarakulwattana

Chulalongkorn University Theses and Dissertations (Chula ETD)

Phytochemical study of the methanol extract of the whole plant of Dendrobium scabrilingue Lindl. (Orchidaceae) resulted in the isolation of a new phenanthrene and a new bisbibenzyl namely dendroscabrols A and B, respectively, along with eight known compounds, identified as (Z)-ferulic acid tetracosyl ester, (E)-ferulic acid tetracosyl ester, gigantol, batatasin III, coelonin, aloifol I, lusianthridin and RF-3192C. The structures of these isolated compounds were determined mainly by spectroscopic data. All isolates were examined for alpha-glucosidase inhibitory activity. Dendroscabrol B and RF-3192C exhibited the most potent activity. In addition, dendroscabrol A, gigantol, coelonin and lusianthridin displayed strong activity compared with the …

Novel Regulatory Mechanisms Of Protein Kinase B On Apoptosis Susceptibility And Cancer Dedifferentiation, Arnatchai Maiuthed

Chulalongkorn University Theses and Dissertations (Chula ETD)

No abstract provided.

Dysregulation Of Human Phase I Enzymes In Apap Overdose Subjects With Low Alt Levels, Aaron Woodall

Honors Theses

Background: Acetaminophen (APAP) is a common analgesic that can cause liver injury and death in high doses. Changes in gene expression following APAP overdose may be more sensitive indicators of liver injury than the current clinical indicator, alanine aminotransferase (ALT). The aim of this study was to examine gene expression of Phase I enzymes in pediatric APAP overdose patients with low ALT levels (<75 lU/L), in order to understand the mechanism of APAP toxicity.

Methods: Blood samples were collected from control patients (no APAP exposure; N=5) and APAP overdose patients (N=S). Using the PAXgene system, RNA was extracted from the blood samples and cDNA was synthesized. Quantitative polymerase chain reaction …

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 …

The Development Of Novel Non-Peptide Proteasome Inhibitors For The Treatment Of Solid Tumors, Zachary C. Miller

Theses and Dissertations--Pharmacy

The proteasome is a large protein complex which is responsible for the majority of protein degradation in eukaryotes. Following FDA approval of the first proteasome inhibitor bortezomib for the treatment of multiple myeloma (MM) in 2003, there has been an increasing awareness of the significant therapeutic potential of proteasome inhibitors in the treatment of cancer. As of 2017, three proteasome inhibitors are approved for the treatment of MM but in clinical trials with patients bearing solid tumors these existing proteasome inhibitors have demonstrated poor results. Notably, all three FDA-approved proteasome inhibitors rely on the combination a peptide backbone and reactive …

Discovery Of Novel Muraymycin Antibiotics And Insight Into The Biosynthetic Pathway, Zheng Cui

Theses and Dissertations--Pharmacy

New antibiotics with novel targets or mechanisms of action are needed to counter the steady emergence of bacterial pathogens that are resistant to antibiotics used in the clinic. MraY, a promising novel target for antibiotic development, initiates the lipid cycle for the biosynthesis of peptidoglycan cell wall, which is essential for the survival of most, if-not-all, bacteria. MraY is an enzyme that catalyzes the transfer and attachment of phospho-MurNAc-pentapeptide to a lipid carrier, undecaprenylphosphate. Muraymycins are recently discovered lipopeptidyl nucleoside antibiotics that exhibit remarkable antibiotic activity against Gram-positive as well as Gram-negative bacteria by inhibiting MraY. We conducted a thorough …

Discovery Of Natural Product Analogs Against Ethanol-Induced Cytotoxicity In Hippocampal Slice Cultures, Meredith A. Saunders-Mattingly

Theses and Dissertations--Psychology

An estimated 13.9% of Americans currently meet criteria for an alcohol (ethanol; EtOH) use disorder (AUD). While there are 4 medications approved by the Food and Drug Administration (FDA) to treat AUD, these treatments have demonstrated poor clinical efficacy. Our ongoing research program encompasses a multi-tiered screening of a natural product library and validation process to provide novel information about the mechanisms underlying EtOH-induced changes in neurobiology and to identify novel chemical scaffolds to be exploited in the development of pharmacological treatments for AUD in a rodent organotypic hippocampal slice culture model. Initial screens of several natural product compounds identified …

The Effects Of Stand-Alone Prescription Drug Plans On Health Care Utilizations, Expenditures And Medication Adherence Among Elderly Medicare Beneficiaries, Jing Yuan

Theses and Dissertations

Since the implementation of Medicare Part D in 2006, a growing body of evidence has shown that Medicare Part D might offset the total healthcare spending by improving the use of prescription drugs. However, little is known about the impact of different types of Part D plans – Stand-alone Prescription Drug Plan (PDPs) and Medicare Advantage Prescription Drug Plan (MA-PDs) – on health care utilizations and expenditures. This dissertation examined the association between the effect in PDPs on health care utilizations as well as expenditures, and medication adherence among elderly Medicare beneficiaries, compared to MA-PDs. Data was pooled from 2006-2010 …

Mechanisms Of Rad51d-Dependent Repair Of Dna And Telomere Damage Induced By Interstrand Crosslinking Agents And Thiopurines, Nicole M. Reilly

Theses and Dissertations

Mutations in homologous recombination (HR) genes increase genomic instability, an enabling characteristic of cancer. However, the status of these same genes can also determine chemotherapy outcomes. RAD51D is a breast and ovarian cancer susceptibility gene that is an important component of HR. Mammalian cells defective for RAD51D have extensive chromosomal aberrations and are more sensitive to the interstrand crosslink-inducing agent mitomycin C (MMC) and the thiopurine 6-thioguanine (6TG). Previously, the RNF138 E3 ubiquitin ligase was identified to promote RAD51D ubiquitination, and loss of RNF138 also increased cellular sensitivity to MMC. Ubiquitination assays were used to show that a 3-ubiquitin modification …

Kv7 Channels Of The Urinary Bladder Smooth Muscle: Functional Roles And Therapeutic Potential, Aaron Provence

Theses and Dissertations

Overactive bladder (OAB) is a pervasive and debilitating condition for which effective therapeutic modalities are lacking. As potential novel pharmacological targets for lower urinary tract dysfunction, our recent studies have demonstrated voltage-gated KV7 channels (KV7.1-KV7.5) to be functionally expressed in detrusor smooth muscle (DSM) of the urinary bladder. Nonetheless, the specific roles of individual KV7 channel subtypes remains poorly understood. Using Western blot, immunocytochemistry, isometric DSM tension recordings, ratiometric fluorescence Ca2+ imaging, and patch-clamp electrophysiology, we demonstrated expression and key physiologic roles for the KV7.2/KV7.3 channels in guinea pig DSM using the novel and selective KV7.2/KV7.3 channel opener N-(2-Chloro-5-pyrimidinyl)-3,4-difluorobenzamide (ICA-069673). …

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 …

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 …

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 …