Pharmacy and Pharmaceutical Sciences Commons^™

Structure Activity Relationship Studies Of Novel Diarylpentanoid Analogs Targeting The Androgen Receptor In Prostate Cancer Cells, Haili Coffin, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

The development of prostate cancer (PCa) relies strongly on the activation of the androgen receptor (AR) signaling pathway by its natural ligand dihydrotestosterone. Furthermore, PCa progression to metastatic disease represents oncogene addiction to AR activity. Androgen ablation therapy is thus a mainstay therapy against this disease, but the development of ligand-independent AR activation and persisting AR expression eventually leads to castration resistant PCa (CRPC). Therefore, down-regulation of AR expression in PCa cells may be an effective therapeutic modality. The diarylpentanoid ca27 has previously been shown to down-regulate AR expression by an unknown mechanism of action. The present work represents a …

Toxic And Essential Trace Element Content Of Commonly Administered Pediatric Oral Medications, Robert A. Yokel, Sarah E. Seger, Jason M. Unrine

Pharmaceutical Sciences Faculty Publications

OBJECTIVES: The aim of this study was to test the hypothesis that commonly administered pediatric oral medications are a significant source of toxic elements. The concentrations of 16 elements were determined in 14 frequently used pediatric oral medications.

METHODS: Samples were prepared for analysis by dilution or nitric acid microwave-assisted digestion and analyzed by inductively coupled plasma mass spectrometry. The intake of each element from administration for 1 week of the medication's maximum recommended daily dose to 6-month-olds was calculated and compared to an exposure guideline for that element. Exposure guidelines used for adverse effects were minimal risk levels, oral …

Activity Of Distinct Growth Factor Receptor Network Components In Breast Tumors Uncovers Two Biologically Relevant Subtypes, Moom Roosan, Shelley M. Macneil, David F. Jenkins, Gajendra Shrestha, Sydney R. Wyatt, Jasmine A. Mcquerry, Stephen R. Piccolo, Laura M. Heiser, Joe W. Gray, W. Evan Johnson, Andrea H. Bild

Pharmacy Faculty Articles and Research

Background
The growth factor receptor network (GFRN) plays a significant role in driving key oncogenic processes. However, assessment of global GFRN activity is challenging due to complex crosstalk among GFRN components, or pathways, and the inability to study complex signaling networks in patient tumors. Here, pathway-specific genomic signatures were used to interrogate GFRN activity in breast tumors and the consequent phenotypic impact of GRFN activity patterns.

Methods
Novel pathway signatures were generated in human primary mammary epithelial cells by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS (G12V), RAF1, BAD). The pathway analysis toolkit Adaptive Signature Selection …

Chronic Neuropsychological Sequelae In A Patient With Nontumorous Anti-Nmda-Receptor Encephalitis, Dong Y. Han, Lisa M. Mason, Aarti Patel, Zhengqiu Zhou, Sarah Phillips, Siddharth Kapoor

Neurology Faculty Publications

Anti-N-methyl-D-aspartate receptor encephalitis is a neurological, autoimmune disorder tightly conceptualized only as recently as the mid-2000s. It presents itself in a combination of psychiatric, neurological, and autonomic features. We observe a unique case with probable earlier episode (prior to the mid-2000s conceptualization of the disease) and a later relapse, accompanying a comprehensive neuropsychological profile tracked after the relapse and subsequent improvement. Neurocognitive findings revealed residual frontal deficits with mood changes even in the state after plasmapheresis. This case is the first to describe posttreatment cognition in anti-NMDAR encephalitis after probable serial autoimmune episodes.

Targeting The Pd-1 Pathway In Pediatric Solid Tumors And Brain Tumors, Lars M. Wagner, Val R. Adams

Pediatrics Faculty Publications

While remarkable advances have been made in the treatment of pediatric leukemia over the past decades, new therapies are needed for children with advanced solid tumors and high-grade brain tumors who fail standard chemotherapy regimens. Immunotherapy with immune checkpoint inhibitors acting through the programmed cell death-1 (PD-1) pathway has shown efficacy in some chemotherapy-resistant adult cancers, generating interest that these agents may also be helpful to treat certain refractory pediatric malignancies. In this manuscript we review current strategies for targeting the PD-1 pathway, highlighting putative biomarkers and the rationale for investigation of these drugs to treat common pediatric tumors such …

Latanoprost And Timolol In Hydrogel Soft Drug-Dispensing Contact Lenses: A Comparative Analysis, Neha Potdar

Virginias Collegiate Honors Council Conference

Glaucoma patients only can instill glaucoma eye drops. This results in 1-7% absorption of the medication. Surveys show that patients forget to take their medication and have difficulty inserting their eye drops. Researchers at the Massachusetts Eye and Ear Infirmary have developed latanoprost drug-dispensing hydrogel soft contact lenses that dispense the drug to help facilitate the process. However, some glaucoma patients do not respond to latanoprost because they have uveitic glaucoma or do not want to experience latanoprost’s ocular side effects. Patients need an alternative which can be inserted into these contact lenses. Another commonly used glaucoma drug is timolol …

Outcomes After Diagnosis Of Mild Cognitive Impairment In A Large Autopsy Series, Erin L. Abner, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Daniela C. Moga, Eseosa T. Ighodaro, Gregory A. Jicha, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Randall L. Woltjer, Julie A. Schneider, Nigel J. Cairns, David A. Bennett, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

OBJECTIVE: To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI).

METHODS: Data were drawn from a large autopsy series (N = 1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States.

RESULTS: Mean follow‐up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group had pathological features resembling those with a final clinical …

Adverse Reactions Of Biological Therapies In Patients With Psoriasis, Maria I. Sârbu, Mircea Tampa, Mădălina I. Mitran, Cristina I. Mitran, Alexandra M. Limbău, Simona R. Georgescu

Journal of Mind and Medical Sciences

Psoriasis is a chronic, immune-mediated disorder characterized by well demarcated, erythematous plaques covered by thick, silvery-white scales, most often located on the knees, elbows, sacral area and scalp. It has a significant impact on the patient's quality of life.

Biological therapies revolutionized the treatment of psoriasis vulgaris but there has been concern regarding the use of those agents due to severe adverse reactions reported in patients receiving TNF-α inhibitors for various inflammatory diseases.

The aim of this paper is to review the most important adverse reactions reported in patients receiving biological treatments. The most common and severe side effects associated …

Journal Of Mind And Medical Sciences: Translational And Integrative Mission, David L. Rowland, Ion G. Motofei

Journal of Mind and Medical Sciences

Initiated four years ago, Journal of Mind and Medical Sciences (J Mind Med Sci.) established the mission to publish papers on mental and medical topics in distinct but closely interrelated domains. The editorial policy especially encourages interdisciplinary and integrative perspectives, being equally focused on basic research and clinical investigations and short reports.

The journal adheres to the philosophy that high quality, original ideas and information should be readily accessible and freely shared within and amongst the scientific community. Accordingly, J Mind Med Sci. is an online, open access, non-for-profit journal which, because of individual/ private support, has levied no charges …

Neurofeedback Or Neuroplacebo?, Robert T. Thibault, Michael Lifshitz, Amir Raz

Psychology Faculty Articles and Research

This scientific commentary refers to ‘Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia’, by Schabus et al.. (doi:10.1093/brain/awx011).

Adverse Events And Treatment Discontinuations Of Antimuscarinics For The Treatment Of Overactive Bladder In Older Adults: A Systematic Review And Meta-Analysis, Scott Martin Vouri, Clark D. Kebodeaux, Paul M. Stranges, Besu F. Teshome

Pharmacy Practice and Science Faculty Publications

Introduction

Antimuscarinics should be used with caution in older adults with overactive bladder (OAB) due to anticholinergic adverse events (AEs). Systematic reviews and meta-analyses (SRMAs) have analyzed safety-related outcomes but have not specified risk in the elderly, the population at highest risk for AEs. The aim of this review is to explore and evaluate AEs and treatment discontinuations in adults 65 or older taking antimuscarinics for OAB.

Methods

Keywords were searched in MEDLINE, EMBASE, SCOPUS, and Cochrane Central Register for Controlled Trials. Randomized controlled trials (RCTs) along with sub-analyses and pooled analyses that compared antimuscarinics to placebo or another antimuscarinic …

Efficacy And Tolerability Of Adjunctive Brivaracetam In Patients With Prior Antiepileptic Drug Exposure: A Post-Hoc Study., Ali A. Asadi-Pooya, Michael R. Sperling, Steve Chung, Pavel Klein, Anyzeila Diaz, Sami Elmoufti, Jimmy Schiemann, John Whitesides

Department of Neurology Faculty Papers

Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) for adjunctive treatment of focal (partial-onset) seizures in adults with epilepsy. This post-hoc analysis was conducted to explore the efficacy of adjunctive BRV in patients with prior levetiracetam (LEV) exposure and whether changes in efficacy were related to the similar mechanism of action of these two drugs. Data were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1-2 AEDs who received placebo or BRV 50-200mg/day without titration over a 12-week treatment period. Patients taking concomitant LEV …

Prospect Of The Use Of Checkpoint Inhibitors In Hepatocellular Cancer Treatments, Ali Raufi

Internal Medicine

Hepatocellular cancer (HCC) is a very fatal disease due to limited therapeutic options as well as due to its association with underlying chronic liver disease in the majority of cases. The immune evasion in HCC signifies a major barrier to the delivery of effective immunotherapy. Sorafenib is the only Food and Drug Administration-approved drug available with an overall response rate of 2%–3% and overall survival of 2.8 months. Chemotherapy has not been used routinely because of the relative refractoriness of advanced HCC. The introduction of immune checkpoint inhibitors (cytotoxic T-lymphocyte antigen 4, programmed death 1, and programmed death-ligand 1) has …

Caphosol For Prevention Of Oral Mucositis In Pediatric Myeloablative Haematopoietic Cell Transplantation., Nathaniel Treister, Michael Nieder, Christina Baggott, Ellen Olson, Lu Chen, Ha Dang, Mark Krailo, Amanda August, Lillian Sung

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The primary objective was to determine whether topically administered Caphosol, rinsed orally four times daily at the initiation of conditioning, reduces the duration of severe oral mucositis (OM) compared with placebo among children and adolescents undergoing haematopoietic cell transplantation (HCT).

METHODS: This was a Children's Oncology Group multicentre randomised double-blinded placebo-controlled clinical trial. Patients between the ages of 4 and 21 years who were scheduled to undergo myeloablative HCT for any indication were randomised to Caphosol or placebo saline rinses four times daily from initiation of conditioning through day +20. Subjects were assessed daily for OM using the World …

Doxorubicin Cytotoxicity In A Human Proximal Tubular Epithelial Cell Line Was Attenuated By The Natural Product Resveratrol, Morghan Schuyler Getty

Theses, Dissertations and Capstones

The cancer chemotherapeutic agent doxorubicin (DOX), Adriamycin, is part of the treatment regimen for breast, ovarian, small cell lung cancer and acute/chronic lymphoid leukemia. Adverse effects associated with DOX are cardiotoxicity and nephrotoxicity. Interventions are needed to reduce DOX nephrotoxicity. Resveratrol (RES) is a phytochemical contained in grapes, berries and nuts, which possesses antioxidant and anticancer properties. This study tested the hypothesis that RES will attenuate DOX renal cytotoxicity in human noncancerous renal proximal tubular epithelial (HK-2) cells and that RES will reduce DOX mediated changes in mitochondrial function. HK-2 cells were plated and grown for 48 hours (h). Cells …

Actionable Patient Safety Solution (Apss) #3c: Improve Prevention Of Severe Hypoglycemia, Jerika Lam, Steven Barker, Michael Ramsay, Ariana Longley, Joe Kiani

Pharmacy Faculty Articles and Research

This report presents a plan of action for introducing a "program to reduce errors in the recognition and treatment of [severe hypoglycemia]".

Actionable Patient Safety Solution (Apss) #3d: Pediatric Adverse Drug Events, Ron Jordan, Jerika Lam, Nathaniel Sims, Anne Lyren, Coco Yang

Pharmacy Faculty Articles and Research

This report presents a plan of action for introducing a "program to reduce the incidence of pediatric adverse drug events (pADEs) and harm ... [that] combine[s] leadership strategies, software (healthcare IT), hardware (drug compounding systems, drug delivery technology, and physiological monitoring systems), and most importantly people (changes in clinical practice, protocols and education)" to protect pediatric patients.

A Comparison Of Sex Differences In Psychotropic Medication Use In Older People With Alzheimer's Disease In The Us And Finland, Daniela C. Moga, Heidi Taipale, Anna-Maija Tolppanen, Antti Tanskanen, Jari Tiihonen, Sirpa Hartikainen, Qishan Wu, Gregory A. Jicha, Danijela Gnjidic

Pharmacy Practice and Science Faculty Publications

Aims—Given the high prevalence of psychotropic medication use in people with dementia and the potential for different prescribing practices in men and women, our study aimed to investigate sex differences in psychotropic medication use in older adults with Alzheimer’s disease (AD) living in the US and Finland.

Methods—We used data collected between 2005 and 2011 as part of the National Alzheimer’s Coordinating Center (NACC) in the US, and Medication use and Alzheimer’s disease (MEDALZ) cohorts in Finland. We evaluated psychotropic medication use (antidepressant, antipsychotic, anxiolytic, sedative, or hypnotic) in participants aged 65 years or older. We employed multivariable …

Gastrointestinal Bleeding Events And Statin Use: A Large Propensity Score-Matched Retrospective Cohort Study, Ashley I. Martinez

Theses and Dissertations--Pharmacy

Literature is conflicting regarding the association between statin use and gastrointestinal (GI) bleeding. This study sought to determine whether there is an association between statin use and GI bleeding by comparing incidence of gastrointestinal events between statin users and an active comparator group.

Data was obtained from a large administrative claims database composed of subjects enrolled in a selection of insurance plans throughout the United States from 2009-2014. New statin users (exposed) and thyroid medication users (active comparator, unexposed) were followed from the baseline period (one year prior to medication initiation) until first event, discontinuation, or disenrollment. Subjects were matched …

The Development Of Bsn272 From Prevention Of Diet-Induced Hyperlipidemia In Mice To A Potential Therapy For Prader-Willi Syndrome In Humans, Jarrod B. Williams

Theses and Dissertations--Pharmacy

While type 2 diabetes mellitus (T2DM) is distinguished as a disorder of blood glucose homeostasis, the vast majority of patients afflicted with this disease in the US present with the entire complement of the metabolic syndrome: abdominal obesity, hypertriglyceridemia, low HDL levels, elevated blood pressure, and elevated fasting plasma glucose. Current guidelines aim to treat each of these disorders, but do so individually even though they are manifestations of common pathologies. In other words, a patient will be prescribed different medications for diabetes, blood pressure, CVD prevention, etc., while the only single treatment aimed at the myriad of disorders together …

Impact Of Time-Varying Treatment Exposures On The Risk Of Venous Thromboembolism In Multiple Myeloma, Joshua D. Brown, Val R. Adams, Daniela C. Moga

Pharmacy Practice and Science Faculty Publications

Multiple myeloma (MM) has one of the highest risks of venous thromboembolism (VTE) of all cancers due to pathologic changes and treatment-related exposures. This study assessed the one-year incidence of VTE in newly diagnosed MM and to determine the baseline and time-varying treatment-related factors associated with VTE risk in a U.S.-based cohort. MM patients were identified and age, gender, and baseline comorbidities were determined. Treatment-related exposures included thalidomide derivatives (IMIDs), proteasome inhibitors, cytotoxic chemotherapy, steroids, erythropoietin-stimulating agents (ESAs), stem cell transplants (SCT), hospitalizations, infection, and central venous catheters (CVC). Multiple statistical models were used including a baseline competing risks model, …

Advances And Perspectives In Genetics Of Congenital Thyroid Disorders Associated With Thyroglobulin Gene Mutations, Héctor M. Targovnik, Cintia E. Citterio, Sofi Siffo, Carina M. Rivolta

Pharmacy Faculty Articles and Research

Dyshormonogenesis due to thyroglobulin (TG) gene mutations is a rare cause of congenital hypothyroidism with an estimated incidence of approximately 1 in 100,000 newborns. The TG gene is organized in 48 exons, spanning over 270 kb on human chromosome 8q24. The human TG mRNA is 8.5 Kb long and the preprotein monomer is composed of a 19 amino acids signal peptide followed by a 2749 residues polypeptide. Until now, one hundred seventeen deleterious mutations in the human TG gene have been identified and characterized, originating structural changes in the protein that alter the normal protein folding, assembly and …

Adoption Of Perioperative Lidocaine Infusion For The Reduction Of Postoperative Pain, Brandon Scott Figueiredo

Doctoral Projects

Laparoscopic capability provides numerous benefits to patients requiring abdominal surgical procedures. However, the use of these techniques has presented the anesthesia provider with a unique set of challenges in terms of perioperative management and postoperative pain reduction. No standardized method has existed to reduce postoperative pain and improve recovery following these procedures. There were three primary goals of this project. The first goal was to conduct a meta-analysis of randomized controlled trials to determine the benefit of the use of intravenous lidocaine infusions to reduce postoperative pain in laparoscopic abdominal surgery. Twelve articles were included in the meta-analysis that pertained …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

Decreasing Cost Associated Medication Nonadherence, Shawn E. Raymond

Doctor of Nursing Practice Scholarly Project

An Abstract of the Scholarly Project by

Shawn E. Raymond

Medication cost is a major contributor for patient medication nonadherence. Take in the fact that a large population lives in poverty, many cannot afford to pay the retail prices associated with purchasing their medications. By incorporating wholesale medications into a charitable health clinic, the reduced cost of medications for treatment of both acute and chronic illnesses could be passed on to those in need thereby decreasing cost associated medication nonadherence. Nurse Practitioners in the state of Kansas are not afforded the privilege to purchase, repackage and distribute or resell wholesale …

Prevalence Of Prescription Opioid Abuse In Patients With Pain, Samuel Godana, Ankoor Biswas, Nebiyu Biru, Abraham Getenet, Biana Leybishkis

Journal of Patient-Centered Research and Reviews

Background: Studies showed that 20% to 30% of opioid analgesic drugs prescribed for chronic pain in the United States are misused, while the rate of opioid addiction is approximately 10%. The study describes methods to identify high-risk behavior and forward recommendations to decrease opioid abuse.

Purpose: To assess prevalence and correlate multiple variables with opioid abuse and to forward appropriate recommendation to decrease the prevalence of opioid abuse in the primary care setting.

Methods: A prospective study was conducted at a primary health care clinic, Aurora Sinai Medical Center (Milwaukee, WI). Over 6 months, a total of 49 consecutive patients …

An Interdisciplinary Process Change: Conversion Of Picc Line Capping Solution From Heparin To Normal Saline, Angela Colella, Brandon Bodager, Frank Spexarth, Natalie Mcdonough, Deb Kastenholz, Paul Grebe

Journal of Patient-Centered Research and Reviews

Background: Heparin-induced thrombocytopenia (HIT) and HIT with thrombosis syndrome (HITTS) are serious conditions. Patients are at increased risk for developing HIT/HITTS with any exposure to heparin, even intravenous line flushes. Patients may be exposed to heparin multiple times each day when they have a peripherally inserted central catheter (PICC) that is flushed and capped with heparin. At Aurora Health Care, heparin is the standard capping solution for PICCs, but with a recent switch to positive pressurized caps, normal saline may be a capping option that reduces patient exposure to heparin.

Purpose: To reduce heparin exposure at a single hospital by …

An Interprofessional Clinical Integrations Pilot Program: Integrating Third-Year Pharmd Students Into Family Medicine Clinics, Eric Gilliam, Pharmd, Arian Hilsendager, Fnp, Erin Hagerman, Pa, Benjamin Kirkley, Md, Benjamin Chavez, Pharmd, Kari Franson, Pharmd

JCIPE Conference

Purpose: Pilot an interprofessional student placement model by entrusting Doctor of Pharmacy students to deliver value-added patient engagement within interprofessional clinical environments.

Background: Beginning in January 2016, pharmacy education standards mandate students actively engage in early patient care experiences with interprofessional teams, thus necessitating new models by which students collaborate with providers in the provision of patient care.

Intervention: Between May and August 2016, two family medicine clinics are incorporating 65 third-year pharmacy students into shared medical patient care visits during an interprofessional-provider introductory pharmacy practice experience (IP Provider IPPE) pilot program. Students engage with patients and …

Olanzapine For Chemotherapy-Induced Nausea And Vomiting, John B. Bossaer

ETSU Faculty Works

Excerpt: Navari and colleagues (July 14 issue)1 report on the use of olanzapine for the prevention of chemotherapy-induced nausea and vomiting.

Selective Anticancer Activity Of Hydroxyapatite/Chitosan-Poly(D,L)-Lactide-Co-Glycolide Particles Loaded With An Androstane-Based Cancer Inhibitor, Nenad Ignjatović, Katarina M. Penov-Gaši, Victoria M. Wu, Jovana J. Ajduković, Vesna V. Kojić, Dana Vasiljević-Radović, Maja Kuzmanović, Vuk Uskoković, Dragab Uskoković

Pharmacy Faculty Articles and Research

In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. ¹H NMR and ¹³C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the …