Pharmacy and Pharmaceutical Sciences Commons^™

Linezolid-Associated Thrombocytopenia In Children With Renal Impairment, Chad A. Knoderer, Kristen R. Nichols, Heather L. Deyoung, Sara J. Jones, Elaine G. Cox

Scholarship and Professional Work – COPHS

Poster presented at ID Week, October 2013, San Francisco, California.

Vancomycin And Gentamicin Pharmacokinetic Alterations In An Adolescent Amputee, Kristen R. Nichols, Kari M. Edison, Michelle D. Rosenbaum, Chad A. Knoderer

Scholarship and Professional Work – COPHS

A 14-year-old male with bilateral above-the-knee amputations presented to our hospital for treatment of a skin and soft-tissue infection. We report the experience of vancomycin and gentamicin therapy in this patient. Because these medications require weight-based dosages and pharmacokinetic monitoring of serum levels, it was necessary to obtain peak and trough levels of the two drugs in order to determine the pharmacokinetic differences in this patient compared to those in an adolescent male without amputations. To our knowledge, this is the first report describing pharmacokinetic differences in an adolescent amputee.

Geriatric Medication Therapy: Weighing The Evidence Versus Best Practice, Lindsay M. Saum, Cathy Ramey

Scholarship and Professional Work – COPHS

Goals: The goal of this article is to provide a review of available evidence for safe prescribing in older adults and recommend medication therapies based on anticipated pharmacokinetic/physiologic changes in this population.

Corneal Gene Therapy: Basic Science And Translational Perspective, Rajiv R. Mohan, Jason T. Rodier, Ajay Sharma

Pharmacy Faculty Articles and Research

Corneal blindness is the third leading cause of blindness worldwide. Gene therapy is an emerging technology for corneal blindness due to the accessibility and immune-privileged nature of the cornea, ease of vector administration and visual monitoring, and ability to perform frequent noninvasive corneal assessment. Vision restoration by gene therapy is contingent upon vector and mode of therapeutic gene introduction into targeted cells/tissues. Numerous efficacious vectors, delivery techniques, and approaches have evolved in last decade for developing gene-based interventions for corneal diseases. Maximizing the potential benefits of gene therapy requires efficient and sustained therapeutic gene expression in target cells, low toxicity, …

Bmp7 Gene Transfer Via Gold Nanoparticles Into Stroma Inhibits Corneal Fibrosis In Vivo, Ashish Tandon, Ajay Sharma, Jason T. Rodier, Alexander M. Klibanov, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

This study examined the effects of BMP7 gene transfer on corneal wound healing and fibrosis inhibition in vivo using a rabbit model. Corneal haze in rabbits was produced with the excimer laser performing -9 diopters photorefractive keratectomy. BMP7 gene was introduced into rabbit keratocytes by polyethylimine-conjugated gold nanoparticles (PEI2- GNPs) transfection solution single 5-minute topical application on the eye. Corneal haze and ocular health in live animals was gauged with stereo- and slit-lamp biomicroscopy. The levels of fibrosis [a-smooth muscle actin (aSMA), F-actin and fibronectin], immune reaction (CD11b and F4/80), keratocyte apoptosis (TUNEL), calcification (alizarin red, vonKossa and osteocalcin), and …

Limited Sampling Estimates Of Epigallocatechin Gallate Exposures In Cirrhotic And Noncirrhotic Patients With Hepatitis C After Single Oral Doses Of Green Tea Extract., Dina Halegoua-De Marzio, Walter K. Kraft, Constantine Daskalakis, Xie Ying, Roy L Hawke, Victor J. Navarro

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Epigallocatechin-3-gallate (EGCG) has antiangiogenic, antioxidant, and antifibrotic properties that may have therapeutic potential for the treatment of cirrhosis induced by hepatitis C virus (HCV). However, cirrhosis might affect EGCG disposition and augment its reported dose-dependent hepatotoxic potential.

OBJECTIVE: The safety, tolerability, and disposition of a single oral dose of EGCG in cirrhotic patients with HCV were examined in an exploratory fashion.

METHODS: Eleven patients with hepatitis C and detectable viremia were enrolled. Four had Child-Pugh (CP) class A cirrhosis, 4 had Child-Pugh class B cirrhosis, and 3 were noncirrhotic. After a single oral dose of green tea extract 400 …

Activation Of Amp-Activated Protein Kinase By 3,39-Diindolylmethane (Dim) Is Associated With Human Prostate Cancer Cell Death In Vitro And In Vivo, Di Chen, Sanjeev Banerjee, Qiuzhi C. Cui, Dejuan Kong, Fazlul H. Sarkar, Q. Ping Dou

Oncology Faculty Publications

There is a large body of scientific evidence suggesting that 3,39-Diindolylmethane (DIM), a compound derived from the digestion of indole-3-carbinol, which is abundant in cruciferous vegetables, harbors anti-tumor activity in vitro and in vivo. Accumulating evidence suggests that AMP-activated protein kinase (AMPK) plays an essential role in cellular energy homeostasis and tumor development and that targeting AMPK may be a promising therapeutic option for cancer treatment in the clinic. We previously reported that a formulated DIM (BR-DIM; hereafter referred as B-DIM) with higher bioavailability was able to induce apoptosis and inhibit cell growth, angiogenesis, and invasion of prostate cancer cells. …

Psychometrics Of The Scale Of Attitudes Toward Physician-Pharmacist Collaboration: A Study With Medical Students., Mohammadreza Hojat, John Spandorfer, Gerald A. Isenberg, Michael J. Vergare, Reza Fassihi, Joseph S. Gonnella

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND: Despite the emphasis placed on interdisciplinary education and interprofessional collaboration between physicians and pharmacologists, no psychometrically sound instrument is available to measure attitudes toward collaborative relationships.

AIM: This study was designed to examine psychometrics of an instrument for measuring attitudes toward physician-pharmacist collaborative relationships for administration to students in medical and pharmacy schools and to physicians and pharmacists.

METHODS: The Scale of Attitudes Toward Physician-Pharmacist Collaboration was completed by 210 students at Jefferson Medical College. Factor analysis and correlational methods were used to examine psychometrics of the instrument.

RESULTS: Consistent with the conceptual framework of interprofessional collaboration, three underlying …

Pharmacokinetic/Pharmacodynamic (Pk/Pd) Modeling Of Anti-Neoplastic Agents, Daniel Lexcen, Ahmed H. Salem, Walid F. Elkhatib, Virginia Haynes, Ayman Noreddin

Pharmacy Faculty Books and Book Chapters

"Development of tumor resistance to chemotherapeutics is related to inherent tumor variations regarding sensitivity to chemotherapeutics and to sub-optimal dosing regimens, including variation in patient pharmacokinetics that result in suboptimal exposure of tumor cells to anti-neoplastic drugs [1, 2]. The rate and extent of drug efficacy depends on the extent of drug exposure at the tumor site and the time above the effective concentration [3]. In vitro models that incorporate these pharmacokinetic and pharmacodynamic (PK/PD) principles to optimize therapeutic response may be considered the method of choice for optimizing dosing schedules before translating data from static assays to animals and …

Inhibition Of Adhesion And Invasion Of Pseudomonas Aeruginosa To Lung Epithelial Cells: A Model Of Cystic Fibrosis Infection, Ayman Noreddin, Ghada Sawy, Walid Elkhatib, Ehab Noreddin, Atef Shibl

Pharmacy Faculty Books and Book Chapters

"Over their life time, CF patients experience multiple infections by various pneumoniacausing bacteria [6]. With more patients surviving to adulthood, chronic infections with Pseudomonas aeruginosa are coming to the forefront as a leading cause of death [7]. Problems presented by infected CF lung are multi-dimensional; the electrolyte balance and pH of the fluids are abnormal. The mucus is thick and of an alternative composition compared to normal lung and may contribute to colonization with Pseudomonas aeruginosa [2, 3, 5]. As such, research is multi-pronged and includes gene therapy to correct the defective protein, amelioration of inflammatory response and thinning of …

Retrospective Comparison Of The Incidence Of Acute Kidney Injury In Patients Treated With Intravenous Polymyxin B Or Intravenous Colistimethate Sodium, Rebecca A. Sumner Pharmd, Jarrod W. Kile Rph, Bcps

Department of Pharmacy

No abstract provided.

Retrospective Evaluation Of Admissions For Chemotherapy-Inducednausea, Vomiting, And Dehydration, Katelin Van Leer Pharmad, Janine Barnaby Rph, Bcop

Department of Pharmacy

No abstract provided.

Nonsteroidal Anti-Inflammatory Drugs Are An Important Cause Of Acute Kidney Injury In Children, Jason M. Misurac, Chad A. Knoderer, Jeffrey D. Leiser, Corina Nilescu, Amy C. Wilson, Sharon P. Andreoli

Scholarship and Professional Work – COPHS

Objective

To characterize nonsteroidal anti-inflammatory drug (NSAID)-associated acute kidney injury (AKI) in children.

Study design

We conducted a retrospective chart review of children diagnosed with AKI through the use of International Classification of Diseases, Ninth Revision diagnosis code 584.5 or 584.9 from January 1999 to June 2010. Medical records were reviewed to confirm the diagnosis of AKI and to quantify NSAID administration. Pediatric RIFLE criteria were used to codify AKI. Patients were not classified as having NSAID-associated AKI if they had a diagnosis explaining AKI or comorbid clinical conditions predisposing to AKI development.

Results

Patients (N = 1015) were identified …

Tissue-Specific Alterations Of Prl-1 And Prl-2 Expression In Cancer, Carmen M. Dumaual, George E. Sandusky, Han Weng Soo, Sean R. Werner, Pamela L. Crowell, Stephen K. Randall

Scholarship and Professional Work – COPHS

The PRL-1 and PRL-2 phosphatases have been implicated as oncogenic, however the involvement of these molecules in human neoplasms is not well understood. To increase understanding of the role PRL-1 and PRL-2 play in the neoplastic process, in situ hybridization was used to examine PRL-1 and PRL-2 mRNA expression in 285 normal, benign, and malignant human tissues of diverse origin. Immunohistochemical analysis was performed on a subset of these. PRL-1 and PRL-2 mRNA expression was also assessed in a small set of samples from a variety of diseases other than cancer. Where possible, associations with clinicopathological characteristics were evaluated. Alterations …

Bone Health Management In Prostate Cancer Patients Receiving Androgen Deprivation Therapy, Vishnuprabha Dhanapal, David J. Reeves

Scholarship and Professional Work – COPHS

Purpose. Patients receiving androgen deprivation therapy undergo a rapid decline in bone mineral density during the first 6 to 12 months of initiating therapy. The World Health Organization has developed and implemented the Fracture Risk Assessment Tool (FRAX) to predict the ten year risk of a major fracture & hip fracture. Additionally, the National Comprehensive Cancer Network and the National Osteoporosis Foundation have developed osteoporosis guidelines. This study aims to characterize the fracture risk (based on the FRAX tool) and the current management of bone health based on national guidelines compliance.

Methods. A retrospective chart review of patients receiving a …

The Fit-Hansa Demonstrates Reliability And Convergent Validity Of Functional Performance In Patients With Shoulder Disorders, Prajyot Kumta, Joy C. Macdermid, Saurabh Mehta, Paul W. Stratford

Physical Therapy Faculty Research

Study

DesignPsychometric study design.

Objectives

To assess the test-retest reliability and convergent validity of the Functional Impairment Test-Hand and Neck/Shoulder/Arm (FIT-HaNSA) in patients with shoulder disorders.

Background

Performance tests that assess functional ability of patients with shoulder disorders can provide useful information for making clinical or return-to-activity decisions. No performance-based shoulder test has yet demonstrated sufficient relevance or clinical measurement properties. The FIT-HaNSA examines upper extremity performance during repetitive tasks that emphasize shoulder reaching and static postures and, therefore, has greater relevance for assessing performance.

Methods

Thirty-six patients with shoulder disorders and 65 healthy controls were recruited for the study. …

Chemotherapy: The Physiological Cost Of A Cure, Megan Ellis

A with Honors Projects

This project focuses on the common long term side effects of cancer treatments, apart from cure. In addition to physiological function changes, it focuses on the chemical composition of chemotherapy drugs.

Vorinostat: A Potent Agent To Prevent And Treat Laser-Induced Corneal Haze, Ashish Tandon, Jonathan C. K. Tovey, Michael R. Waggoner, Ajay Sharma, John W. Cowden, Daniel J. Gibson, Yuanjing Liu, Gregory S. Schultz, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE—This study investigated the efficacy and safety of vorinostat, a deacetylase (HDAC) inhibitor, in the treatment of laser-induced corneal haze following photorefractive keratectomy (PRK) in rabbits in vivo and transforming growth factor beta 1 (TGFβ1) -induced corneal fibrosis in vitro.

METHODS—Corneal haze in rabbits was produced with −9.00 diopters (D) PRK. Fibrosis in cultured human and rabbit corneal fibroblasts was activated with TGFβ1. Vorinostat (25 μm) was topically applied once for 5 minutes on rabbit cornea immediately after PRK for in vivo studies. Vorinostat (0 to 25 μm) was given to human/rabbit corneal fibroblasts for 5 minutes or 48 …

Attitudes, Beliefs, And Practices Of Providers And Key Opinion Leaders On Emergency Contraception In India, M.E. Khan, Deepthi S. Varma, Isha Bhatnagar, Anvita Dixit, Martha Brady

Reproductive Health

The Population Council undertook this study to assess the knowledge, attitudes, and practices regarding emergency contraception (ECP) among providers in public and private facilities and pharmacies in India. The objectives of the study were to: assess providers' knowledge of ECP's biological mechanism; understand providers' knowledge and attitudes about ECP's safety, effectiveness, and availability as an OTC drug; and identify providers' definitions of “repeated use” and profiling women who are “repeated users” of ECP. This study's findings show that most providers, including doctors and some KOLs, were incorrectly informed about ECP's mechanism of action. Service guidelines are necessary for accurate and …

Providers' And Key Opinion Leaders' Attitudes, Beliefs, And Practices Regarding Emergency Contraception In Nigeria, Babatunde A.O. Ahonsi, Salisu Mohammed Ishaku, Araoyinbo Idowu, Ayodeji Oginni

Reproductive Health

Despite significant progress in product development, procurement, and distribution in the past few decades, emergency contraception’s (EC) capacity to benefit many women in countries such as Nigeria is hampered by a number of potential barriers, that are not well understood. The Population Council, with support from the International Consortium for Emergency Contraception, documented EC-related knowledge, attitudes, and practices among providers in Nigeria as well as perceptions of key opinion leaders who help shape the policy environment for EC and family planning in general. Findings suggest significant gaps in Nigeria, potentially necessitating continuous training and re-training to help dispel misperceptions and …

Gene Therapy In The Cornea: 2005--Present, Rajiv R. Mohan, Jonathan C. K. Tovey, Ajay Sharma, Ashish Tandon

Pharmacy Faculty Articles and Research

Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders. The efficacy of gene therapy is contingent upon vector and mode of therapeutic DNA introduction into targeted cells/tissues. The cornea is an ideal tissue for gene therapy due to its ease of access and relative immune-privilege. Considerable progress has been made in the field of corneal gene therapy in last 5 years. Several new gene transfer vectors, techniques and approaches have evolved. Although corneal gene therapy is still in its early stages of development, the potential of gene-based interventions to treat …

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 …

Attenuation Of Corneal Myofibroblast Development Through Nanoparticle-Mediated Soluble Transforming Growth Factor-Β Type Ii Receptor (Stgfβrii) Gene Transfer, Ajay Sharma, Jason T. Rodier, Ashish Tandon, Alexander M. Klibanov, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: To explore (i) the potential of polyethylenimine (PEI)-DNA nanoparticles as a vector for delivering genes into human corneal fibroblasts, and (ii) whether the nanoparticle-mediated soluble extracellular domain of the transforming growth factor–β type II receptor (sTGFβRII) gene therapy could be used to reduce myofibroblasts and fibrosis in the cornea using an in vitro model.

Methods: PEI-DNA nanoparticles were prepared at a nitrogen-to-phosphate ratio of 30 by mixing linear PEI and a plasmid encoding sTGFβRII conjugated to the fragment crystallizable (Fc) portion of human immunoglobulin. The PEI-DNA polyplex formation was confirmed through gel retardation assay. Human corneal fibroblasts (HCFs) were …

Key Opinion Leaders' Views Regarding Emergency Contraception In India, M.E. Khan, Isha Bhatnagar, Deepthi S. Varma, Anvita Dixit

Reproductive Health

This policy brief explores the views of key opinion leaders (KOLs) in the field of reproductive health and family welfare on provision of emergency contraception (ECPs). The study’s objective was to gain a better understanding of how the attitudes and beliefs of KOLs might influence policy and program implementation, either encouraging or opposing ECP promotion and service delivery. Results suggest strong support by the majority of KOLs to continue the sale of ECP as an over-the-counter drug. KOLs also emphasized the importance of comprehending and addressing the main barriers to ECP provision and use: poor knowledge, lack of training, moral …

Providers' Attitudes And Practices Regarding Emergency Contraception In India: Key Findings, M.E. Khan, Isha Bhatnagar, Deepthi S. Varma, Anvita Dixit

Reproductive Health

This policy brief reports key findings of a study in India that explored providers’ knowledge of how emergency contraception (ECP) works and its safety and effectiveness, their perceptions of the frequency of repeat use, their provision of ECP, and their attitudes toward women who seek it. Many of the findings of this study are encouraging. Most providers believed that ECP is an effective and safe method to prevent pregnancy and that it cannot induce abortion, and half supported the over-the-counter provision of ECP. Nevertheless, the study revealed many biases and gaps in knowledge. Recommendations include a number of ways to …

Novel Amino Acid Transporter-Targeted Radiotracers For Breast Cancer Imaging, Fanlin Kong

Dissertations and Theses (Open Access)

Breast cancer is the most common malignancy among women in the world. Its 5-year survival rate ranges from 23.4% in patients with stage IV to 98% in stage I disease, highlighting the importance of early detection and diagnosis. ¹⁸F-2-Fluoro-2-deoxy-glucose (¹⁸F-FDG), using positron emission tomography (PET), is the most common functional imaging tool for breast cancer diagnosis currently. Unfortunately, ¹⁸F-FDG-PET has several limitations such as poorly differentiating tumor tissues from inflammatory and normal brain tissues. Therefore, ¹⁸F-labeled amino acid-based radiotracers have been reported as an alternative, which is based on the fact that tumor cells uptake …

Effect Of Preventive Zinc Supplementation On Linear Growth In Children Under 5 Years Of Age In Developing Countries: A Meta-Analysis Of Studies For Input To The Lives Saved Tool, Aamer Imdad, Zulfiqar Ahmed Bhutta

Woman and Child Health

Introduction:Zinc plays an important role in cellular growth, cellular differentiation and metabolism. The results of previous meta-analyses evaluating effect of zinc supplementation on linear growth are inconsistent. We have updated and evaluated the available evidence according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria and tried to explain the difference in results of the previous reviews.

Methods:

A literature search was done on PubMed, Cochrane Library, IZiNCG database and WHO regional data bases using different terms for zinc and linear growth (height). Data were abstracted in a standardized form. Data were analyzed in two ways i.e. weighted …

Efficacy Of Limited Cefuroxime Prophylaxis In Pediatric Patients After Cardiovascular Surgery, Chad A. Knoderer, Elaine G. Cox, Michelle D. Berg, Andrea H. Webster, Mark W. Turrentine

Scholarship and Professional Work – COPHS

Purpose The efficacy of limited cefuroxime prophylaxis in pediatric patients after cardiovascular surgery was evaluated.

Methods All patients age 18 years or younger who underwent cardiovascular surgery and received postoperative care from the cardiovascular surgery team between February and July 2006 (preintervention group) and between August 2006 and January 2007 (postintervention group) were eligible for study inclusion. Patients were excluded if they did not receive cefuroxime as postoperative prophylaxis, had a preexisting infection, underwent cardiac transplantation or extracorporeal membrane oxygenation, or underwent delayed sternal closure. The preintervention group received prolonged cefuroxime prophylaxis, and the postintervention group received 24 hours of …

Cefuroxime Pharmacokinetics In Pediatric Cardiovascular Surgery Patients Undergoing Cardiopulmonary Bypass, Chad A. Knoderer, Sarah A. Saft, Scott G. Walker, Markl D. Rodefeld, Mark W. Turrentine, John W. Brown, Daniel P. Healy, Kevin M. Sowinski

Scholarship and Professional Work – COPHS

Objectives

The objective of this study was to determine the pharmacokinetics of cefuroxime in children undergoing cardiopulmonary bypass (CPB) for cardiovascular surgery.

Design

A prospective study.

Setting

A tertiary pediatric teaching hospital.

Participants

Infants and children undergoing CPB were enrolled in the study.

Intervention

An initial dose (mean, 24.2 ± 1.6 mg/kg) of cefuroxime was administered before surgical incision, and a second dose (mean, 14.4 ± 7.9 mg/kg) was administered in the CPB prime solution. Serial blood samples were obtained before, during, and after the CPB process. Samples were shipped on dry ice to the analytic laboratory and concentrations determined …

Assessment Of The Validity Of Reported Antibiotic Allergic Reactions In Pediatric Patients, Lauren E. Miller, Chad A. Knoderer, Elaine G. Cox, Martin B. Kleinman

Scholarship and Professional Work – COPHS

Study Objective. To determine whether a reported antibiotic allergy was likely to have been immunologically mediated.

Design. Questionnaire-based study.

Setting. Tertiary care, freestanding children's hospital.

Patients. One hundred patients aged 1 month-18 years for whom guardians reported an allergy to an antibiotic at the time of hospital admission between October 2009 and March 2010.

Intervention. Guardians of the patients were interviewed by using a standardized allergy assessment questionnaire.

Measurements and Main Results. Based on answers to the questionnaire, the reported allergic reactions were categorized to determine if they were true allergies or adverse reactions. Among the 100 patients, reported allergies …