Medicine and Health Sciences Commons^™

Heart Failure Transition Of Care Program: The Pharmacist’S Role In Reducing Readmissions, Joseph Favatella, Pharmd Candidate 2013, Joanne Heil, Pharmd, Bcps

College of Pharmacy Faculty Papers

Presented at: ASHP Mid-Year Clinical Meeting in Las Vegas.

Introduction & Background

Current Trends¹

•Approximately 19.6% of Medicare patients are readmitted to the hospital within 30 days

•These readmissions accounted for $15 billion of Medicare spending in 2009

Changes Coming

•As part of the Affordable Care Act, Medicare will not be reimbursing hospitals for patients readmitted within 30 days of discharge

•Hospitals have already begun improving discharge protocols to provide a greater continuity of care and minimize the financial loss of future readmissions

A Model²

•Boston University Medical Center's Re-Engineered Discharge (RED) was the first program to improve …

The Use Of Glucarpidase In An Open-Label Treatment Protocol As Adjunctive Treatment For A Patient With Delayed Methotrexate Elimination, Cheryl A. Abbas, Pharmd, Anne Marie Valorie-Oberle, Bs, Pharmd, Bcop

College of Pharmacy Faculty Papers

Presented at: ASHP Clinical MidYear Meeting in Las Vegas.

Background

Methotrexate (MTX)

• Cytotoxic agent that competitively inhibits dihydrofolate reductase (DHFR), the intracellular enzyme responsible for converting folic acid to reduced folate inhibitors, necessary for DNA synthesis
• Used since 1948 in the treatment of various malignancies and as a disease-modifying agent in rheumatoid arthritis and psoriasis
• High-dose mexthotrexate (HDMTX) began in 1960s solely or in combination with other chemotherapeutic agents

Methotrexate Toxicity

• Almost exclusively cleared through the kidneys
  • Precipitation of drug occurs in the renal tubules
  • Prolonged elevations of systemic MTX concentrations results in potential serious toxicity
• Increased use of HDMTX …

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 …

Dysregulation Of Mir-31 And Mir-21 Induced By Zinc Deficiency Promotes Esophageal Cancer, Hansjuerg Alder, Cristian Taccioli, Hongping Chen, Yubao Jiang, Karl Smalley, Paolo Fadda, Hatice G. Ozer, Kay Huebner, John Farber, Carlo M. Croce, Louise Fong

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Presented at: Hallmarks and Cancer Conference, October 29-31 in San Francisco.

And AICR Annual Meeting, November 1-2, 2012.

Dietary zinc (Zn) deficiency (ZD) in rats induces an inflammatory gene signature that fuels esophageal squamous cell cancer (ESCC). Using nanoStringTM technology, we show that the inflammation is accompanied by altered expression of specific microRNAs in esophagus, as well as skin, lung, pancreas, liver, prostate, and PBMC, predictive of disease development. Particularly, the ZD esophagus has a microRNA signature resembling human ESCC/tongue SCC miRNAomes with overexpression of miR-31 and miR-21 and downregulation of their respective tumor suppressor targets PPP2R2A and …

Mk-0448, A Specific Kv1.5 Inhibitor: Safety, Pharmacokinetics And Pharmacodynamic Electrophysiology In Experimental Animal Models And In Humans., Behzad B. Pavri, Howard E Greenberg, Walter K. Kraft, Nicole Lazarus, Joseph J Lynch, Joseph J Salata, Mark T Bilodeau, Christopher P Regan, Gary Stump, Li Fan, Anish Mehta, John A Wagner, David E Gutstein, Daniel Bloomfield

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: -We evaluated the viability of I(Kur) as a target for maintenance of sinus rhythm in patients with a history of atrial fibrillation through the testing of MK-0448, a novel I(Kur) inhibitor. METHODS AND RESULTS: -In vitro MK-0448 studies demonstrated strong inhibition of I(Kur) with minimal off-target activity. In vivo MK-0448 studies in normal anesthetized dogs demonstrated significant prolongation of the atrial refractory period compared with vehicle controls without affecting the ventricular refractory period. In studies of a conscious dog heart failure model, sustained AF was terminated with bolus intravenous MK-0448 doses of 0.03 and 0.1 mg/kg. These data led …

Interprofessional Education In Didactic And Experiential Settings At The Jefferson School Of Pharmacy, Elena M. Umland, Cynthia A. Sanoski, Emily R. Hajjar, Bhavik Shah

College of Pharmacy Faculty Papers

Presented at: 2012 Annual Meeting of the American Association of Colleges of Pharmacy in Kissimmee, Florida.

Objective:

To evaluate the various IPE offerings at a new school of pharmacy at a large academic medical center.

Pharmacologic Management Of The Opioid Neonatal Abstinence Syndrome., Walter K. Kraft, John N Van Den Anker

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Opioid use in pregnant women has increased over the last decade. Following birth, infants with in utero exposure demonstrate signs and symptoms of withdrawal known as the neonatal abstinence syndrome (NAS). Infants express a spectrum of disease, with most requiring the administration of pharmacologic therapy to ensure proper growth and development. Treatment often involves prolonged hospitalization. There is a general lack of high-quality clinical trial data to guide optimal therapy, and significant heterogeneity in treatment approaches. Emerging trends in the treatment of infants with NAS include the use of sublingual buprenorphine, transition to outpatient therapy, and pharmacogenetic risk stratification.

Effect Of Concomitant Medications Affecting Gastric Ph And Motility On Posaconazole Tablet Pharmacokinetics, Walter K. Kraft, P. Chang, Mlps Van Iersel, H. Waskin, G. Krishna, W. Kersemaekers

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Poster presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy (52^nd ICAAC) held in San Francisco 9/9-9/12

Background: Posaconazole (POS) oral suspension is an extended-spectrum triazole that should be taken with food to maximize absorption. A new POS tablet formulation has demonstrated improved bioavailability over oral suspension in healthy adults in the fasting state. This study evaluated the effect of concomitant medications altering gastric pH (antacid, ranitidine, and esomeprazole) and motility (metoclopramide) on the pharmacokinetics of POS tablet.

Methods: This was a prospective, open-label, 5-way crossover study in 20 healthy volunteers. In each treatment period, a single 400-mg (100 …

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 …

Creating A Model Antigen System To Test The Mechanism Of Gcc-Specific Tolerance, Patrick Ihejirika

Summer Training Program in Cancer Immunotherapy

Immunotherapeutics for colorectal cancer have been under investigation for decades. Unfortunately, a recent meta-analysis has revealed only a 1% response rate for all immunotherapeutic trials in colorectal cancer, highlighting the need for improved immunotherapeutic target antigens which are tumor-specific, immunogenic, and shared by patients. However, to produce immunological responses targeting tumor/self antigens, one has to overcome tolerance, which has constituted an obstacle to previous studies. Guanylyl cylcase C is the index cancer-mucosa antigen, an emerging class of tumor antigens in colorectal cancer. As a mucosa-restricted antigen, GCC is amenable to immunological targeting and uniquely suited for immunotherapy of colorectal cancers. …

Phosphorylation Of Vasodilator-Stimulated Phosphoprotein Ser239 Suppresses Filopodia And Invadopodia In Colon Cancer., David S Zuzga, Joshua Pelta-Heller, Peng Li, Alessandro Bombonati, Scott A Waldman, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

In colorectal cancer, the antitumorigenic guanylyl cyclase C (GCC) signalome is defective reflecting ligand deprivation from downregulation of endogenous hormone expression. Although the proximal intracellular mediators of that signal transduction system, including cyclic guanosine monophosphate (cGMP) and cGMP-dependent protein kinase (PKG), are well characterized, the functional significance of its distal effectors remain vague. Dysregulation of ligand-dependent GCC signaling through vasodilator-stimulated phosphoprotein (VASP), an actin-binding protein implicated in membrane protrusion dynamics, drastically reduced cGMP-dependent VASP phosphorylation levels in colorectal tumors from patients. Restoration of cGMP-dependent VASP phosphorylation by GCC agonists suppressed the number and length of locomotory (filopodia) and invasive (invadopodia) …

Molecular Staging Individualizing Cancer Management, Alex Mejia, Stephanie Schulz, Terry Hyslop, David S. Weinberg, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Although the most important prognostic and predictive marker in colorectal cancer is tumor cells in lymph nodes, ∼30% of patients who are node-negative die from occult metastases. Molecular staging employing specific markers and sensitive detection technologies has emerged as a powerful platform to assess prognosis in node-negative colon cancer. Integrating molecular staging into algorithms that individualize patient management will require validation and the definition of relationships between occult tumor cells, prognosis, and responses to chemotherapy. J. Surg. Oncol. 2012; 105:468-474. © 2012 Wiley Periodicals, Inc.

Copyright © 2012 Wiley Periodicals, Inc.

The Value Proposition Of Molecular Medicine., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Individualized patient management is rapidly evolving, driven by the emergence of insights in discovery, development, regulatory, and comparative effectiveness sciences.^1-4 The pace of discovery is accelerating, enabled by platforms, including “omics”, stem cell biology, network medicine, and medical and biological informatics that provide unanticipated insights into pathophysiology.^{2, 4-6} The integration of these paradigms has established a model for identifying the mechanistic underpinnings of disease, offering novel opportunities to individualize diagnostics that shape how modern therapies are deployed, including markers of disease prognosis, clinical predictors of therapeutic responses, and molecular determinants that optimize clinical management.^7-10 Importantly, deconvolution of …