Pharmacy and Pharmaceutical Sciences Commons^™

Retrospective Study To Identify Predictors Of Withdrawal In Pediatric Intensive Care Patients On Long-Term Sedation, Lindsay Fakete Pharmd, Jenny Boucher Pharmd, Jd, Bcps, Scott Wheatley Md

Department of Pharmacy

No abstract provided.

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. …

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 …

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 …

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.

Chronic Outpatient Sildenafil Therapy For Pulmonary Hypertension In A Child After Cardiac Surgery, Chad A. Knoderer, E. S. Ebenroth, J. W. Brown

Chad A. Knoderer

We report the case of a 14-month-old male with d-transposition of the great arteries, ventricular septal defect, and pulmonary hypertension successfully treated with long-term sildenafil following cardiac surgery. To our knowledge, this is the first published report of long-term sildenafil treatment in a child after corrective cardiac surgery.

Survey Of Congenital Heart Surgeons’ Preferences For Antimicrobial Prophylaxis For Pediatric Cardiac Surgery Patients, Chad A. Knoderer, Emily M. Anderson, Elaine G. Cox

Chad A. Knoderer

Patients with congenital heart defects are a unique population with generally immature immune systems. Fragility in the postoperative period may contribute to surgical site infections (SSIs), a life threatening complication for this population. The need for postoperative antimicrobial prophylaxis for these patients is a standard of care that is indisputable. When choosing an antimicrobial regimen for surgical prophylaxis, consideration should be given to balancing the prevention of nosocomial infections, avoiding emergence of bacterial resistance, and minimizing drug toxicities and cost.

Fenoldapam For Acute Kidney Injury In Children, Chad A. Knoderer, Jeffrey D. Leiser, Corina Nailescu, Mark W. Turrentine, Sharon P. Andreoli

Chad A. Knoderer

We report two cases of children with severe cardiomyopathy requiring treatment with ventricular assist devices who developed acute kidney injury and were treated with fenoldopam. Therapy with fenoldopam appeared successful in one case in that renal replacement therapy was avoided with improvement in urine output and renal function. These are the first reported cases of fenoldopam use in children with acute kidney injury receiving mechanical circulatory support.

Systematic Review Of Potential Health Risks Posed By Pharmaceutical, Occupational And Consumer Exposures To Metallic And Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide And Its Soluble Salts, Calvin C. Willhite, Nataliya A. Karyakina, Robert A. Yokel, Nagarajkumar Yenugadhati, Thomas M. Wisniewski, Ian M. F. Arnold, Franco Momoli, Daniel Krewski

Pharmaceutical Sciences Faculty Publications

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007).

Challenges encountered in carrying out the present review reflected the experimental use of different physical …

The Role Of Ape/Ref-1 In Hepatocellular Carcinoma Progression, Zhen Yang, Sun Yang, Bobbye J. Misner, Feng Liu-Smith, Frank L. Meyskens

Pharmacy Faculty Articles and Research

Hepatocellular carcinoma (HCC) is responsible for a third of the estimated cancer-caused deaths worldwide. To deeply understand the mechanisms controlling HCC progression is of primary importance to develop new approaches for treatment. Apurinic/apyrimidinic endonuclease-1/redox effector factor 1 (APE/Ref-1) has been uncovered elevated in various types of cancer, including HCC. Additionally, HCC progression is always correlated with elevated copper (Cu). Our previous data demonstrated that Cu treatment initiated APE/Ref-1 expression and its downstream targets. Therefore, we hypothesized that APE/Ref-1 may be involved in HCC progression through mediating the effect of Cu to its signaling cascades. Following different treatments, human HCC cell …

Production Of Recombinant Human Coagulation Factor Ix By Transgenic Pig, Weijie Xu

Department of Chemical and Biomolecular Engineering: Theses and Student Research

Hemophilia B is the congenital bleeding disorder caused by deficiency in functional coagulation factor IX (FIX) and about 28,000 patients worldwide in 2012. And current treatment is restricted to protein-replacement therapy, which required FIX concentrates for patients’ life-time. Approximately 1 billion units FIX were consumed in 2012. However, still about 70-80% patients, mostly in developing countries, received inadequate or no treatment because of the unavailable and/or unaffordable FIX concentrates. Considering safety reasons, e.g. transmission of blood-borne diseases, the recombinant human FIX (rFIX) is recommended other than the plasma-derived FIX. However, only one rFIX is currently available on the market. The …

A Filtration System That Greatly Reduces Aluminum In Calcium Gluconate Injection, Usp Used To Prepare Parenteral Nutrition Solutions, Robert A. Yokel, Wesley R. Harris, Christopher D. Spilling, Vasiliy P. Abramov, Jason M. Lone, Robert J. Kuhn

Pharmaceutical Sciences Faculty Publications

OBJECTIVE: The study objective was to reduce aluminum (Al) in Calcium Gluconate Injection, US Pharmacopeia (USP) used in the preparation of parenteral nutrition (PN) solutions.

METHODS: A flow-through filter containing an immobilized chelator that complexes Al from Calcium Gluconate Injection, USP as it flows through the filter was designed, refined by design modifications, and extensively tested. When a small-volume parenteral vial containing 100 mL of Calcium Gluconate Injection, USP is connected on the inlet side of the filter, and the outlet side is connected to an evacuated receiving vial, the filtered solution is drawn into the receiving vial. This constitutes …

Natural Products As Therapeutic Agents In Cancer Treatment, Trevor Stump, Lauren P. Williams, Brittany Santee, Chelsae Ward, Rachel Kunze, Denise S. Simpson, Samson Amos

The Research and Scholarship Symposium (2013-2019)

Cancer accounts for 25% of deaths in the United States, and brain tumors greatly contribute to this percentage. However, relative to other types of cancers, brain tumors prove difficult to treat because they are heterogeneous, highly proliferative, highly invasive, and resistant to the traditional cancer treatments of chemotherapy and radiotherapy. Past studies have shown that flavonoids and curcuminoids, two classes of compounds derived from natural sources, are effective in inhibiting the development and metastasis of breast and lung cancer cells. Research has also indicated that these compounds have potential for treating brain tumors.

The purpose of this research is to …

Tumor Radiation Therapy Creates Therapeutic Vaccine Responses To The Colorectal Cancer Antigen Gucy2c., Matthew Witek, Erik S Blomain, Michael Sullivan Magee, Bo Xiang, Scott A Waldman, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

PURPOSE: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined.

METHODS AND MATERIALS: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses …

Knowledge Of And Perceived Need For Evidence-Based Education About Antipsychotic Medications Among Nursing Home Leadership And Staff, Celeste Lemay, Kathleen Mazor, Terry Field, Jennifer Donovan, Abir Kanaan, Becky Briesacher, Sarah Foy, Leslie Harrold, Jerry Gurwitz, Jennifer Tjia

Jennifer Tjia

BACKGROUND/OBJECTIVES: Antipsychotic use is common in US nursing homes, despite evidence of increased risk of morbidity and mortality, and limited efficacy in older adults with dementia. Knowledge, attitudes, and beliefs regarding antipsychotic use among nursing home staff are unclear. The study aim was to describe nursing home leadership and direct care staff members' knowledge of antipsychotic risks, beliefs and attitudes about the effectiveness of antipsychotics and nonpharmacologic management of dementia-related behaviors, and perceived need for evidence-based training about antipsychotic medication safety. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Survey of leadership and direct care staff of nursing homes in Connecticut was conducted …

Influence Networks Based On Coexpression Improve Drug Target Discovery For The Development Of Novel Cancer Therapeutics, Nadia M. Penrod, Jason H. Moore

Dartmouth Scholarship

Background: Thedemandfornovelmolecularlytargeteddrugswillcontinuetoriseaswemoveforwardtowardthe goal of personalizing cancer treatment to the molecular signature of individual tumors. However, the identification of targets and combinations of targets that can be safely and effectively modulated is one of the greatest challenges facing the drug discovery process. A promising approach is to use biological networks to prioritize targets based on their relative positions to one another, a property that affects their ability to maintain network integrity and propagate information-flow. Here, we introduce influence networks and demonstrate how they can be used to generate influence scores as a network-based metric to rank genes as potential drug targets. …

Vaccine-Preventable Diseases In Travelers, Edith Mirzaian, Jeffery A. Goad, Ani Amloian, Fady Makar

Pharmacy Faculty Articles and Research

Travel to the developing world is increasing among those from developed countries, placing them at risk for vaccine preventable and non-vaccine preventable diseases. From 2007-2011, the GeoSentinel Network reported 737 returned travelers with a vaccine preventable disease. While it is essential that clinicians use vaccines when available for a disease of risk, they should also be aware that the vast majority of diseases acquired by travelers are non-vaccine preventable. The vaccine preventable diseases can be divided into routine travel vaccines, special travel vaccines and routine vaccines used for travel. The routine travel vaccines include Hepatitis A and B, typhoid; special …

Gold(Iii)-Dithiocarbamato Peptidomimetics In The Forefront Of The Targeted Anticancer Therapy: Preclinical Studies Against Human Breast Neoplasia, Chiara Nardon, Sara M. Schmitt, Huanjie Yang, Jian Zuo, Delores Fregona, Q. Ping Dou

Oncology Faculty Publications

Since the serendipitous discovery of cisplatin, platinum-based drugs have become well-established antitumor agents, despite the fact that their clinical use is limited by many severe side-effects. In order to both improve the chemotherapeutic index and broaden the therapeutic spectrum of current drugs, our most recent anti-neoplastic agents, Au(III) complexes, were designed as carrier-mediated delivery systems exploiting peptide transporters, which are up-regulated in some cancers. Among all, we focused on two compounds and tested them on human MDA-MB-231 (resistant to cisplatin) breast cancer cell cultures and xenografts, discovering the proteasome as a major target both in vitro and in vivo. …

Cinacalcet Administration By Gastrostomy Tube In A Child Receiving Peritoneal Dialysis, Kristen R. Nichols, Chad A. Knoderer, Bethanne Johnston, Amy C. Wilson

Scholarship and Professional Work – COPHS

A 2-year-old male with chronic kidney disease with secondary hyperparathyroidism developed hypercalcemia while receiving calcitriol, without achieving a serum parathyroid hormone concentration within the goal range. Cinacalcet 15 mg (1.2 mg/kg), crushed and administered via gastrostomy tube, was added to the patient’s therapy. This therapy was effective in achieving targeted laboratory parameters in our patient despite instructions in the prescribing information that cinacalcet should always be taken whole.

Optimized Antimicrobial Dosing Strategies: A Survey Of Pediatric Hospitals, Chad A. Knoderer, Kristen R. Nichols, Elaine G. Cox

Scholarship and Professional Work – COPHS

Background

Extended-interval aminoglycoside (EIAG) and extended- and continuous-infusion β-lactam (EIBL and CIBL) dosing strategies are increasingly used in adults, but pediatric literature is limited.

Objective

The objective of this study was to describe the use of EIAG, EIBL, and CIBL dosing in pediatric hospitals in the USA.

Study Design, Setting, and Participants

A national survey of children’s hospitals was conducted. A single practitioner from each target hospital was identified through the Children’s Hospital Association. Practice-based survey questions identified whether hospitals utilize EIAG, EIBL, and CIBL dosing.

Main Outcome Measure

The main outcome measure was the percentage utilization of the dosing …

Ceftriaxone Potentiates Warfarin Activity Greater Than Other Antibiotics In The Treatment Of Urinary Tract Infections, Lindsay M. Saum, Ryan P. Balmat

Scholarship and Professional Work – COPHS

Background: The cephalosporin class has been associated with an increased risk of bleeding among elderly patients receiving warfarin. Urinary tract infections (UTI) are the most prevalent infection in elderly patients.

Objective: To determine the extent of interaction between antibiotics used in the treatment of UTI, particularly specific cephalosporins and warfarin.

Methods: A retrospective chart review was conducted on chronic warfarin patients with a diagnosis of UTI treated with ceftriaxone, a first-generation cephalosporin, penicillin, or ciprofloxacin. The primary outcome was the comparison of the extent of international normalized ratio (INR) change from baseline between each antibiotic group.

Results: The ceftriaxone group …