Medicine and Health Sciences Commons^™

Cross-Sector Review Of Drivers And Available 3rs Approaches For Acute Systemic Toxicity Testing, Troy Seidle, Sally Robinson, Tom Holmes, Stuart Creton, Pilar Prieto, Julia Scheel, Magda Chlebus

Troy Seidle, PhD

Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or …

Humane Society International’S Global Campaign To End Animal Testing, Troy Seidle

Troy Seidle, PhD

The Research & Toxicology Department of Humane Society International (HSI) operates a multifaceted and science-driven global programme aimed at ending the use of animals in toxicity testing and research. The key strategic objectives include: a) ending cosmetics animal testing worldwide, via the multinational Be Cruelty-Free campaign; b) achieving near-term reductions in animal testing requirements through revision of product sector regulations; and c) advancing humane science by exposing failing animal models of human disease and shifting science funding toward human biology-based research and testing tools fit for the 21st century. HSI was instrumental in ensuring the implementation of the March 2013 …

Evaluation And Revision Of An Introduction To Experiential Rotations Course, Eliza A. Dy, Sarah Nisly

Sarah A. Nisly

The objectives of this study were to evaluate the perceived student value of topics taught in Butler University’s Introduction to Experiential Rotations (RX500) course, implement course revisions to address any perceived weaknesses, and to reassess the course following implementation of those course revisions. Advanced Pharmacy Practice Experience (APPE) students from Butler University’s 2012 doctorate of pharmacy class were initially surveyed to assess the perceived usefulness and design of RX500. Based on the findings of the initial data, course revisions were developed and implemented for the following semester’s RX500 course. In order to assess for potential changes in the perceived value …

Distribution Of Propranolol In Periocular Tissues: A Comparison Of Topical And Systemic Administration, Jinsong Hao, Michael B. Yang, Hongzhou Liu, S. Kevin Li

Jinsong Hao

Purpose: Oral propranolol has become a promising treatment of capillary hemangiomas (CHs) despite concerns of side effects associated with systemic beta-blockers. The objective of this study was to investigate the distribution of propranolol in periocular tissues and in plasma after topical application of propranolol as compared with intravenous and oral administration of propranolol. Methods: Each rabbit received propranolol as ophthalmic solution (1%) in one eye (1.5 mg dose), intravenous injection (1.5 mg dose), or commercially available propranolol oral solution (5 mg dose). The periocular tissues (e.g., eyelids and extraocular muscles) and blood were collected and assayed for propranolol. Results:After topical …

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

Saurabh Mehta

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. …

Concurrent Validation Of The Dash And The Quickdash In Comparison To Neck-Specific Scales In Patients With Neck Pain, Saurabh Mehta, Joy Macdermid, Lisa Carlesso, Colleen Mcphee

Saurabh Mehta

Study Design. Concurrent validity study. Objective. To examine the validity of the Disabilities of Arm, Shoulder, and Hand (DASH) and the QuickDASH in patients with neck pain in comparison with the Neck Disability Index (NDI), the Cervical Spine Outcome Questionnaire (CSOQ), and the Visual Analogue Scale (VAS) for pain. To examine the agreement between the DASH and the QuickDASH and assess whether the QuickDASH can be used instead of full DASH in patients with neck pain. Summary of Background Data. NDI is commonly used for measuring neck-related disability in patients with neck pain; but it does not offer to assess …

Considering A New Paradigm For Alzheimer’S Disease Research, Gillian R. Langley

Gill Langley, PhD

Using Alzheimer’s disease as a case study, this review argues that it might be time to consider a new paradigm in medical research and drug discovery. The existing framework is overly dependent on often unvalidated animal models, particularly transgenic mice. Translational success remains elusive and costly late-stage drug failure is common. The conventional paradigm tends to overlook species differences and assumes that animal-based findings are generally applicable to humans. Could pathways-based research using advanced human-specific models probed with new tools, including those of systems biology, take centre stage? The current transition in chemical toxicology to a 21st-century paradigm could be …

Analysis Of Anti-Xa Concentrations In Patients On Treatment Dose Enoxaparin: A Retrospective Chart Review, Lauren Levine, Nicole Pallme, Erik Angelotti, Dane L. Shiltz

Dane L. Shiltz

The purpose of this retrospective chart review was to determine the correlation between full weight-based enoxaparin use and the frequency of anti-Xa concentrations within the defined therapeutic range; to ascertain if anti-Xa monitoring is being appropriately ordered in relation to the timing of enoxaparin dose (after 3 consistent therapeutic doses and 3-5 hours post-dose); to establish if the evidence-based recommended dose adjustment protocol that was studied in the pediatric population was utilized; and if this yielded anti-Xa concentrations within the target range (0.6 – 1.1 IU/mL) for an adult population. The data may suggest a lack of correlation between BMI …

Correlation Of Treatment Dose Enoxaparin With Anti-Xa Concentrations In Adult Hemodialysis Inpatients, Paul E. Brumley, Miroslav A. Anguelov, Jason P. Hecht, Dane L. Shiltz

Dane L. Shiltz

Enoxaparin, a low-molecular-weight-heparin, is being used in hemodialysis patients despite a lack of guideline or manufacturer dose recommendations. Due to enoxaparin’s renal excretion, the possibility of accumulating anti-Xa concentrations in hemodialysis patients using enoxaparin creates a hemorrhagic risk, calling for more research. The objectives of this study are to determine the correlation between treatment dose enoxaparin use and anti-Xa concentrations within the defined therapeutic range in patients receiving chronic, scheduled hemodialysis to determine the degree of change in anti-Xa concentrations in those cases where a concentration was obtained before and after a specific hemodialysis session, and to determine if there …

Hemopericardium And Cardiac Tamponade Associated With Dabigatran Use, Eliza Dy, Dane Shiltz

Dane L. Shiltz

OBJECTIVE: To describe 2 cases of hemopericardium following treatment with dabigatran. CASE SUMMARIES: A 70-year-old male with a history of dabigatran use presented with cough, fatigue, and bloody stools. The patient had a large hyperdense pericardial effusion caused by accumulation of bloody fluid, leading to hypotension and shock. Approximately 1000 mL of hemorrhagic fluid was drained from the pericardial space. A 77-year-old female was admitted for treatment of pneumonia and atrial fibrillation. Dabigatran was initiated and, after 6 doses, the patient developed abdominal pain, respiratory distress, and shock. She was diagnosed with pericardial effusion leading to cardiac tamponade. Pericardiocentesis and …

Use Of Cilostazol For Secondary Stroke Prevention: An Old Dog With New Tricks?, Alex J. Ansara, Dane L. Shiltz, Jennifer B. Slavens

Dane L. Shiltz

OBJECTIVE: To evaluate the safety and efficacy of cilostazol for secondary prevention of non-cardioembolic ischemic stroke. DATA SOURCES: PubMed and MEDLINE searches were performed (January 1970-September 2011) using the key words cilostazol, antiplatelet, aspirin, acetylsalicylic acid, secondary stroke prevention, ischemic stroke, intracerebral hemorrhage, intracranial, cerebrovascular accident, and transient ischemic attack. Additionally, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: Articles published in English and relevant primary literature evaluating the efficacy and safety of cilostazol in the secondary prevention of atherosclerotic ischemic stroke were included. DATA SYNTHESIS: Antiplatelet therapy plays a vital role in the multifaceted approach …

Back Talk: The Medicine Cabinet, Dane Shiltz

Dane L. Shiltz

Presenation to pharmacists at Butler CE Symposium, June 2012, Indianapolis, Indiana.

Appropriate Management Of Migraines, Dane L. Shiltz

Dane L. Shiltz

Presenation to pharmacists at Butler CE Symposium, June 2012, Indianapolis, Indiana.

A Retrospective Comparison Of Daptomycin Thrice-Weekly Versus Q48h Dosing In Hemodialysis Patients With Vancomycin-Resistant Enterococcus (Vre) Or Methicillin-Resistant Staphylococcus Aureus (Mrsa) Bacteremia, Katie L. Axford, Dane L. Shiltz

Dane L. Shiltz

Background. Multi-drug resistant bacteria are a growing concern in healthcare. Daptomycin is being used with increasing frequency in the treatment of vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) bacteremias in hemodialysis (HD) patients. Thrice-weekly dosing of daptomycin in this population would allow for coordination of dosing with common outpatient HD schedules. The aim of this study is to determine if thrice-weekly dosing of daptomycin is equivalent to dosing every 48 hours in patients receiving chronic intermittent hemodialysis. Equivalence will be assessed with regard to microbiological cure, clinical cure, hospital length of stay, and mortality. Methods. All patients with positive …

System-Wide Implementation Of The Use Of An Extended-Infusion Piperacillin/Tazobactam Dosing Strategy: Feasibility Of Utilization From A Children's Hospital Perspective, Kristen Nichols, Chad Knoderer, Elaine Cox

Chad A. Knoderer

Background

Use of extended infusions of piperacillin/tazobactam (PT) in adult patients has been described, but data in children are limited.

Objective

The goal of this study was to determine the feasibility of using an extended-infusion PT dosing strategy as the standard of care in a children's hospital.

Methods

This was a prospective observational study of patients aged >30 days who received PT after admission to a freestanding, tertiary care children's hospital. After institution of an extended-infusion PT dosing protocol as the standard dosing option, patients receiving PT were prospectively assessed for presence of and reasons for changes in dosing regimen. …

Use Of Sildenafil To Facilitate Weaning From Inhaled Nitric Oxide In Children With Pulmonary Hypertension Following Surgery For Congenital Heart Disease, Jaclyn E. Lee, Simon C. Hillier, Chad A. Knoderer

Chad A. Knoderer

Pulmonary hypertension frequently complicates the postoperative management of patients after congenital cardiac surgery. Inhaled nitric oxide is an effective treatment option, but rebound pulmonary hypertension can occur upon its withdrawal. Sildenafil may facilitate its withdrawal by restoring cyclic guanosine monophosphate availability via phosphodiesterase-5 inhibition. The purpose of this study was to evaluate the use of sildenafil in facilitating weaning from inhaled nitric oxide after congenital cardiac surgery in patients who had previously failed weaning, and to compare the effects of sildenafil on pulmonary and systemic hemodynamics. Children who received sildenafil after cardiovascular surgery during a 23-month period at Riley Hospital …

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

Chad A. Knoderer

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

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

Chad A. Knoderer

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 …

Cefepime Neurotoxicity In An Adolescent Cystic Fibrosis Patient With Aminoglycoside-Induced Acute Kidney Injury, Kristen R. Nichols, Danielle M. Brown, Chad A. Knoderer, Sharon P. Andreoli

Chad A. Knoderer

Objective: To describe a case of cefepime neurotoxicity in an adolescent with cystic fibrosis and aminoglycoside-associated acute kidney injury (AKI). Case Summary: A 15-year-old, 46-kg male with cystic fibrosis (CF) and chronic sinusitis was admitted to the hospital for CF exacerbation. The patient was subsequently discharged to complete home antibiotic therapy with intravenous gentamicin and cefepime. Thirteen days after discharge, while still receiving intravenous antibiotics, the patient presented to an outside hospital complaining of vomiting, fatigue, decreased appetite, and decreased urine output. The patient was diagnosed with AKI and was transferred to our institution, where he displayed signs and symptoms …

Evaluating The Duration Of Post-Operative Cefuroxime Prophylaxis On Infectious Outcomes In Pediatric Cardiovascular Surgery Patients., Chad A. Knoderer, Michelle D. Berg, Andrea H. Webster, Elaine G. Cox

Chad A. Knoderer

Abstract of poster presented at: Pediatric Academic Societies Annual Meeting; May 2010; Vancouver, British Columbia.

Outcomes Of Extended-Infusion Piperacillin/Tazobactam In Pediatric Patients., Kristen Nichols, Katie Andricopulos, Ashley Crumby, Elaine Cox, Chad Knoderer

Chad A. Knoderer

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

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

Chad A. Knoderer

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 …

A Randomized, Controlled Trial Of Catheter-Related Infectious Event Rates Using Antibiotic-Impregnated Catheters Versus Conventional Catheters In Pediatric Cardiovascular Surgery Patients, Elaine G. Cox, Chad A. Knoderer, Aimee Jennings, John W. Brown, Mark D. Rodefeld, Scott G. Walker, Mark W. Turrentine

Chad A. Knoderer

We conducted a randomized, controlled clinical trial to determine whether a difference in catheter-associated blood stream infection (CABSI) incidence existed between children who underwent cardiac surgery and had a central venous catheter impregnated with minocycline and rifampin versus those who had a conventional, nonimpregnated catheter after cardiac surgery. Due to a lower number of infections than expected, the study was terminated early. Among 288 evaluable patients, the rates of CABSI and line-related complications were similar between the 2 groups.

Sildenafil For The Treatment Of Pulmonary Hypertension In Pediatric Patients, Alice Huddleston, Chad Knoderer, Jennifer Morris, Eric Ebenroth

Chad A. Knoderer

Sildenafil is a phosphodiesterase 5 inhibitor widely used for the treatment of pulmonary hypertension in children. Despite limited available safety and efficacy evidence, use of sildenafil continues to increase. To date, sildenafil use for pediatric pulmonary hypertension has been characterized for 193 children through 16 studies and 28 case series and reports. The primary efficacy data suggest that sildenafil is beneficial for facilitating the weaning of inhaled nitric oxide in children after cardiac surgery. Compiled safety data suggest that sildenafil is well tolerated among children with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease. This …

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

Chad A. Knoderer

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 …

Impact Of Decmedetomidine On Opioid And Benzodiazepine Dosing Requirements In Children., Amy E. Helvie, Chad A. Knoderer, Iftekhar D. Kalsekar, Brandon T. Kibby, Michael S. Mazurek

Chad A. Knoderer

Poster presented at: Annual Update on Pediatric Cardiovascular Disease; February 2008; Scottsdale Arizona.

Pharmacokinetics Of Cefuroxime Are Not Significantly Altered By Cardiopulmonary Bypass In Children, Chad Knoderer, Sarah Saft, Scott Walker, Daniel Healy, Kevin Sowinski

Chad A. Knoderer

Poster presented at: SPA/AAP PEDIATRIC ANESTHESIOLOGY 2010 - Winter Meeting; April 2010; San Antonio, TX.

Efficacy Of Limited Cefuroxime Prophylaxis In Pediatric Patients After Cardiovascular Surgery, Chad Knoderer, Elaine Cox, Michelle Berg, Andrea Webster, Mark Turrentine

Chad A. Knoderer

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 …

Are Elevated Vancomycin Serum Trough Concentrations Achieved Within The First 7 Days Of Therapy Associated With Acute Kidney Injury In Children?, Chad A. Knoderer, Kristen R. Nichols, Kelsey C. Lyon, Megan M. Veverka, Amy C. Wilson

Chad A. Knoderer

Background In 2008, the empiric vancomycin dosing recommendation in children at our institution was changed from 40 to 60 mg/kg per day. Subsequently, an increased incidence of acute kidney injury (AKI) in patients receiving vancomycin was suspected. The objective of this study was to evaluate AKI in children receiving vancomycin and to determine risk factors for AKI development. Methods Medical records of patients aged 30 days through 17 years who received vancomycin for at least 72 hours between January and December 2007 (40 mg/kg per day) and January and December 2010 (60 mg/kg per day) were reviewed. Patients with cystic …

Clinical Issues Surrounding Once-Daily Aminoglycoside Dosing In Children, Chad A. Knoderer, Julie A. Everett, William F. Buss

Chad A. Knoderer

Aminoglycoside antibiotics are first-line treatment for many infectious diseases in the pediatric population and are effective in adults. The traditional dosing interval in children is every 8–12 hours. Studies in adults reported equivalent efficacy and equal or less toxicity with once-daily regimens. Despite many studies in the adult population, this approach has yet to become standard practice in most pediatric hospitals. Reasons for lack of acceptance of this strategy in children include rapid aminoglycoside clearance, unknown duration of postantibiotic effect, safety concerns, and limited clinical and efficacy data.