bluuebunny/crossref_metadata_2025 huggingface dataset:
Tachyphylaxis Associated with Continuous Cisatracurium versus Pancuronium Therapy
Authors: Kanji Salmaan , Barletta Jeffrey F. , Janisse James J. , Kruse James A. , Devlin John W.
Published: June 2004

Study Objectives. To compare dosing requirements over time among patients receiving continuous cisatracurium versus pancuronium therapy, and to identify factors that may account for changes in pancuronium versus cisatracurium infusion requirements over time.

Design. Retrospective, comparative cohort analysis.

Setting. A tertiary level 1 trauma center.

Patients. Forty‐five consecutive adult patients who were admitted to intensive care units at our institution from January 1998–August 2000 and received continuous cisatracurium or pancuronium therapy for at least 48 hours.

Measurements and Main Results. Dosing requirements of patients treated with pancuronium or cisatracurium were recorded over time throughout the treatment period. Factors that could affect dosing requirements of a neuromuscular blocking agent (NMBA) were stratified as time invariant (admitting service, acute physiology and chronic health evaluation II score, duration of mechanical ventilation, pressure control ventilation, baseline hepatic or renal insufficiency, thermal injury, train‐of‐four assessment, and concurrent drug administration or disorders affecting neuromuscular transmission) or time variant (concurrent sedation and narcotic analgesia therapy; serum magnesium, potassium, and creatinine concentrations; arterial pH level; temperature; peak airway pressure; and partial pressure of oxygen:fraction of inspired oxygen ratio). Hierarchical linear modeling was used to compare the dosing requirements and to identify confounders affecting the relationship. The infusion rate escalation for the cisatracurium group was greater (0.39 μg/kg/min; 95% confidence interval [CI] 0.22–0.56; 23 patients) than for the pancuronium group (−0.06 μg/kg/min; 95% CI −0.24‐0.12; 22 patients; p<0.001) and was associated with an average daily cost/patient significantly higher (p<0.001) with cisatracurium ($258 ± $114) than pancuronium ($11 ± $5). Confounder analysis revealed that only the admitting service and the number of times the NMBA infusion was suspended because no twitch was detected differed between groups. Neither of these confounders significantly affected the temporal relationship between cisatracurium and pancuronium infusion rates.

Conclusion. Dosing requirements increase over time at a significantly greater rate for cisatracurium than pancuronium infusions. Tachyphylaxis with cisatracurium is associated with substantial drug‐related costs and is not accounted for by various disease‐, patient‐, and therapy‐related factors. Further investigation is required to elucidate the mechanisms and risk factors underlying this phenomenon.
Topiramate and Weight Loss in Patients with Neurodevelopmental Disabilities
Authors: Brown Rex O. , Orr Carla D. , Hanna Debra L. , Williams John E. , Dickerson Roland N.
Published: June 2004

Study Objective. To characterize weight changes in patients with neurodevelopmental disabilities who received topiramate.

Design. Retrospective, observational study.

Setting. State‐supported developmental center.

Patients. Fifteen patients with neurodevelopmental disabilities who received topiramate therapy.

Measurements and Main Results. Monthly weights for 1 year after the start of topiramate therapy were recorded. Mean body weight at drug initiation differed significantly compared with the nadir weight during the next 12 months (52.2 ± 7.5 vs 49.9 ± 7.2 kg, p<0.02). Twelve patients who were receiving ad libitum oral diets demonstrated a significant decrease in body weight (52.1 ± 7.5 vs 49.0 ± 7.3 kg, p<0.01), whereas the three patients who received enteral nutrition through enterostomy did not experience significant weight loss.

Conclusion. Weight loss is common in patients with neurodevelopmental disabilities who receive topiramate. Since patients who received oral diets lost weight whereas those receiving enteral nutrition did not, decreased nutrient intake is the likely cause of weight loss.
Nonsteroidal Antiinflammatory Drug Starter Packs for Chronic Musculoskeletal Pain
Authors: Voris John C. , Phillips Cynthia M. , Voris Cynthia T.
Published: June 2004

Study Objective. To determine whether prescribing a nonsteroidal antiinflammatory drug (NSAID) starter pack for chronic musculoskeletal pain expedites the process of finding an appropriate drug for a given patient.

Design. Prospective patient interviews.

Setting. Veterans Affairs Medical Center.

Patients. Sixty‐four patients with chronic musculoskeletal pain were prescribed NSAID starter packs. Of those, 42% were interviewed and their data evaluated.

Intervention. Between March and June 2001, patients received starter packs containing 1‐week supplies of the following NSAIDs: ibuprofen, salsalate, etodolac, naproxen, sulindac, and piroxicam. The patients took one drug each week, then returned to their providers to receive a prescription for the agent that was considered most effective and tolerable.

Measurements and Main Results. Patients assessed pain each day based on a numeric pain‐rating scale. During telephone interviews, seven patients reported better pain control when they were able to select a drug from the starter pack than when they were prescribed a specific drug by their providers. Providers rated the starter pack as easy to use by patients and generally effective for finding the best NSAID for a particular patient. Drugs prescribed after completing the starter pack were salsalate 25.9%, piroxicam 22.2%, etodolac 14.8%, ibuprofen 14.8%, naproxen 11.1%, celecoxib 7.4%, and an opiate 3.7%.

Conclusion. The NSAID starter pack appears to be a successful method for quickly and easily finding an NSAID that is effective and tolerated.
Olanzapine‐Associated Diabetes Mellitus
Authors: Koller Elizabeth A. , Doraiswamy P. Murali
Published: June 2004

Study Objective. To explore the clinical characteristics of hyperglycemia in patients treated with olanzapine.

Design. Retrospective, epidemiologic survey of spontaneously reported adverse events related to olanzapine therapy.

Setting. Government‐affiliated drug evaluation center.

Patients. Two hundred thirty‐seven patients with olanzapine‐associated diabetes or hyperglycemia.

Intervention. One hundred ninety‐six cases from January 1994‐May 15, 2001, were identified with the United States Food and Drug Administration's MedWatch Drug Surveillance System, and 41 cases published through May 15, 2001, were identified with MEDLINE or through meeting abstracts.

Measurements and Main Results. Of the 237 cases, 188 were new‐onset diabetes, 44 were exacerbations of preexistent disease, and 5 could not be classified. Mean patient age for newly diagnosed cases was 40.7 ± 12.9 years and male:female ratio was 1.8. Seventy‐three percent of all cases of hyperglycemia appeared within 6 months of start of olanzapine therapy. Eighty patients had metabolic acidosis or ketosis, 41 had glucose levels of 1000 mg/dl or greater, and 15 patients died. When olanzapine was discontinued or the dosage decreased, 78% of patients had improved glycemic control. Hyperglycemia recurred in 8 of 10 cases with rechallenge.

Conclusions. Number of reports, temporal relationship to start of olanzapine therapy, relatively young age, and improvement on drug withdrawal suggest that olanzapine may precipitate or unmask diabetes in susceptible patients.
New Cholesterol Guidelines, New Treatment Challenges
Authors: McKenney James M.
Published: June 2004

Coronary heart disease (CHD) is the largest single killer of Americans. Epidemiologic trials have indicted low‐density lipoprotein cholesterol (LDL) as directly correlating with CHD events, and clinical trials confirmed that lipid‐lowering therapy decreases the risk of CHD events. The literature also indicates that only about 18% of these patients are treated to their goal LDL levels. New guidelines from the National Cholesterol Education Program extend the LDL‐lowering recommendations, add a new non‐high‐density lipoprotein cholesterol (non‐HDL) goal for patients with hyper‐triglyceridemia, and increase the number of drug‐eligible patients from about 15 to 36 million. Most of those who are eligible for lipid‐altering drug therapy have the highest CHD risk and require the most aggressive treatment to achieve goals. This presents a challenge to clinicians: how best to achieve LDL and non‐HDL goals. Statins are the most effective agents for lowering LDL and one of the most effective for lowering non‐HDL. This efficacy and the ability to reduce CHD risk were well documented in a number of randomized clinical trials. When statin monotherapy fails to achieve goals, a bile acid resin, niacin, or both may be added to lower LDL further, or a fibrate, niacin, or fish oils may be added to lower non‐HDL further. Drugs are under development that may enhance our ability to reach LDL and non‐HDL goals. Included are a group of so‐called super statins, rosuvastatin and pitavastatin; agents that interfere with cholesterol or bile acid transport in the gut, such as ezetimibe; and dual peroxisome proliferator‐activated receptor agonists that have both fibrate and thiazolidinedione‐like effects.
Administration of Glycoprotein IIb‐IIIa Inhibitors in Patients with ST‐Segment Elevation Myocardial Infarction
Authors: Dobesh Paul P. , Kasiar Jennifer B.
Published: June 2004

Patients with ST‐segment elevation acute myocardial infarction require immediate reperfusion therapy. Reperfusion therapy can be provided by either pharmacologic or mechanical means. Pharmacologic reperfusion therapy consists of administering fibrinolytics, whereas mechanical reperfusion consists of performing percutaneous intervention, usually with stent placement. Each approach has been shown to decrease mortality, but each has disadvantages in establishing flow in the infarct‐related artery. Regardless of the approach, during an acute myocardial infarction, activation and externalization of glycoprotein (GP) IIb‐IIIa receptors occur on the surface of platelets. The GP IIb‐IIIa inhibitors block the binding of fibrinogen to these platelet receptors. These inhibitors have been investigated in combination with both reperfusion strategies. The goal of adding GP IIb‐IIIa inhibitor therapy to either reperfusion approach is to obtain better early, complete, and sustained reperfusion. Subsequently, this should lead to better clinical outcomes for patients with ST‐segment elevation acute myocardial infarction. Although no mortality benefit has been seen with the addition of GP IIb‐IIIa inhibitor therapy, ischemic complications have been reduced significantly.
Darbepoetin‐α: A Review of the Literature
Authors: Overbay Debra K. , Manley Harold J.
Published: June 2004

Anemia is a chronic condition that affects many patients with chronic kidney disease (CKD). These patients often require recombinant human erythropoietin (rHuEPO) to stimulate bone marrow to produce red blood cells. The agent often has to be administered 2–3 times/week for maximum efficacy. A new product, darbepoetin‐α, is a hyperglycosylated erythropoiesis‐stimulating protein that has a longer terminal half‐life than rHuEPO (25.3 vs 8.5 hrs), which allows for less frequent dosing. At an equivalent dosage as rHuEPO, darbepoetin‐α maintains hemoglobin values within target range and has a similar adverse effect profile. It is safe and effective for treatment of anemia of CKD. Pharmacoeconomic and quality‐of‐life studies are warranted to determine the compound's overall benefit.
Safety and Efficacy of Controlled‐Release Oxycodone: A Systematic Literature Review
Authors: Rischitelli D. Gary , Karbowicz Sean H.
Published: June 2004

Prescriptions for controlled‐release oxycodone, a narcotic analgesic, recently contributed to a dramatic increase in pharmacy costs for a large private insurance company. To determine whether this agent offered clinical benefits over other available drugs that would justify its significantly greater cost, a systematic review of 16 clinical trials was undertaken. The review suggested that immediate‐release and controlled‐release preparations of oxycodone have similar efficacy and comparable side effect profiles. Controlled‐release oxycodone has the advantage of less frequent dosing than immediate‐release oxycodone; however, other agents may be dosed infrequently at much lower costs. For patients requiring a controlled‐release opioid treatment, controlled‐release morphine and methadone should be considered because they appear to be as effective as oxycodone and cost considerably less. Controlled‐release oxycodone may be appropriate for some patients, particularly if they cannot tolerate other controlled‐release or long‐acting opioid analgesics.
Secretin Treatment for Autistic Disorder: A Critical Analysis
Authors: Patel Nick C. , Yeh Jun Y. , Shepherd Marvin D. , Crismon M. Lynn
Published: June 2004

We assessed evidence of the effects of secretin on behavior in individuals with autistic disorder. Articles were obtained through a MEDLINE search of the English‐language literature from January 1966–November 2001; all investigations and case reports on the topic were included. Press releases obtained from the World Wide Web also were included. Secretin, a gastrointestinal hormone, is suggested to improve autistic symptoms, particularly social function and communication. Two formulations, porcine and synthetic human secretin, were evaluated in humans. A small body of literature and popular belief in autistic disorder communities supported the agent's efficacy. A number of controlled clinical trials did not show improvement in autistic symptoms with secretin compared with placebo, possibly indicating no role for the drug in autistic disorder.
Drug‐Related Visits to the Emergency Department: How Big Is the Problem?
Authors: Patel Payal , Zed Peter J.
Published: June 2004

Objectives. To review the literature concerning drug‐related problems that result in emergency department visits, estimate the frequency of these problems and the rates of hospital admissions, and identify patient risk factors and drugs that are associated with the greatest risk.

Methods. A systematic search of MEDLINE (January 1966–December 2001), EMBASE (January 1980–December 2001), and PubMed (January 1966–December 2001) databases for full reports published in English was performed. The Ottawa Valley Regional Drug Information Service database of nonindexed pharmacy journals also was searched.

Results. Data from eight retrospective and four prospective trials retrieved indicated that as many as 28% of all emergency department visits were drug related. Of these, 70% were preventable, and as many as 24% resulted in hospital admission. Drug classes often implicated in drug‐related visits to an emergency department were nonsteroidal antiinflammatory drugs, anticonvulsants, antidiabetic drugs, antibiotics, respiratory drugs, hormones, central nervous system drugs, and cardiovascular drugs. Common drug‐related problems resulting in emergency department visits were adverse drug reactions, noncompliance, and inappropriate prescribing.

Conclusion. Drug‐related problems are a significant cause of emergency department visits and subsequent resource use. Primary caregivers, such as family physicians and pharmacists, should collaborate more closely to provide and reinforce care plans and monitor patients to prevent drug‐related visits to the emergency department and subsequent morbidity and mortality.
Thiazolidinedione‐Induced Edema
Authors: Niemeyer Nancee V. , Janney Laurel M.
Published: June 2004

Edema is an adverse event associated with thiazolidinedione therapy. The potential for mild‐to‐moderate peripheral edema with thiazolidinedione is known, especially in patients who have heart failure or use insulin. Our experience reveals that patients who do not have heart failure or do not use insulin also can develop moderate‐to‐severe edema that necessitates discontinuation of the thiazolidinedione. A 77‐year‐old man developed ankle, hand, and facial swelling 2 weeks after starting rosiglitazone. After discontinuing the drug, his edema resolved. A 75‐year‐old man developed bilateral lower leg edema 6 months after switching from troglitazone to pioglitazone. He was hospitalized for 51 days and, after aggressive diuresis and discontinuation of pioglitazone, was discharged with a weight loss of 30 pounds. A 53‐year‐old man developed lower leg edema 4 weeks after rosiglitazone was increased from 4 mg once/day to 4 mg twice/day. Rosiglitazone was discontinued and the edema resolved. Until the mechanism of action responsible for fluid overload is known, we suggest that thiazolidinediones be administered with caution in all patients.
Central Nervous System Adverse Effects with Efavirenz: Case Report and Review
Authors: Puzantian Talia
Published: June 2004

Efavirenz is a nonnucleoside reverse transcriptase inhibitor that can be given with other antiretroviral agents for the treatment of human immunodeficiency virus infection. A 47‐year‐old man with acquired immunodeficiency syndrome developed severe depression and suicidal ideation necessitating psychiatric hospitalization and antidepressant therapy. The symptoms occurred in temporal relation to the introduction of efavirenz into his highly active antiretroviral therapy regimen. Similar serious psychiatric adverse effects have been associated with this agent. Clinicians should monitor for central nervous system adverse effects in all patients taking efavirenz.
CYP2D6 Inhibition by Selective Serotonin Reuptake Inhibitors: Analysis of Achievable Steady‐State Plasma Concentrations and the Effect of Ultrarapid Metabolism at CYP2D6
Authors: Lam Y. W. Francis , Gaedigk Andrea , Ereshefsky Larry , Alfaro Cara L. , Simpson Joe
Published: June 2004

Study Objective. To assess the correlation between plasma concentrations of four commonly administered selective serotonin reuptake inhibitors (SSRIs) and the magnitude of cytochrome P450 (CYP) 2D6 inhibition.

Design. Prospective analysis.

Setting. University‐affiliated research laboratory.

Patients. Thirty‐two healthy, drug‐free volunteers.

Intervention. Subjects were randomized to four groups and received daily administration of either fluoxetine 60 mg (as a loading dose), fluvoxamine 100 mg, paroxetine 20 mg, or sertraline 100 mg for 8 days.

Measurements and Main Results. The urinary concentration ratio of dextromethorphan:dextrorphan (interpreted as an in vivo index of CYP2D6 activity) was determined for each subject before and after the 8 days of receiving SSRIs. Plasma SSRI trough concentrations were measured on days 6–9. The CYP2D6 genotype was determined in a subject with an undetectable paroxetine concentration. Inhibition of CYP2D6 correlated significantly with plasma concentrations of paroxetine and fluoxetine. In contrast, no significant correlations emerged between CYP2D6 inhibition and plasma concentrations of sertraline or fluvoxamine. The subject with an undetectable paroxetine concentration was found to carry at least three functional CYP2D6 genes.

Conclusions. For paroxetine and fluoxetine, plasma concentrations and dosage strongly influence the magnitude of enzyme inhibition. The potential of paroxetine (a CYP2D6 substrate) as an inhibitor may be affected by the genotypes and metabolic capacities of individual subjects.
Bivalirudin: A Direct Thrombin Inhibitor for Percutaneous Transluminal Coronary Angioplasty
Authors: Wiggins Barbara S. , Spinler Sarah , Wittkowsky Ann K. , Stringer Kathleen A.
Published: June 2004

The treatment of patients with acute coronary syndromes has changed dramatically over the last several years. Most patients now undergo some form of percutaneous coronary intervention (PCI), which includes either stent placement or percutaneous transluminal coronary angioplasty (PTCA). Along with new medical interventions for acute coronary syndromes comes the need for new antithrombotic therapies. Combination therapy with antiplatelet agents (aspirin, adenosine diphosphate inhibitors), glycoprotein (GP) IIb‐IIIa receptor inhibitors, and anticoagulants (unfractionated heparin or low‐molecular‐weight heparins) is administered, depending on the type of intervention and severity of the coronary lesion. Bivalirudin is a direct thrombin inhibitor that recently was approved as an alternative to heparin in patients undergoing PTCA. Compared with unfractionated heparin, bivalirudin reduces the rate of death, myocardial infarction, or revascularization, with a concurrent reduction in bleeding. This agent offers promise as a replacement for unfractionated heparin in PCI and is being studied in comparison with unfractionated heparin plus GP IIb‐IIIa receptor inhibitors in patients undergoing intracoronary stent placement.
Thalidomide for the Treatment of Relapsed and Refractory Multiple Myeloma
Authors: Cool Rita M. , Herrington Jon D.
Published: June 2004

Thalidomide is the first drug in over 20 years to demonstrate clinically significant activity in patients with multiple myeloma. Although the survival rate has not improved with conventional chemotherapy over the last 30 years, thalidomide has produced favorable responses in patients for whom most available therapies have failed, such as those whose disease was resistant or relapsed after standard and high‐dose treatments. Despite the risk of adverse effects such as sedation and constipation, thalidomide has become an alternative therapy for patients with relapsed or refractory disease. New trials with thalidomide administered alone and in combination with other agents seem to show promise in patients with multiple myeloma, as do preliminary studies with thalidomide derivatives.
Do Butalbital‐Containing Products Have a Role in the Management of Migraine?
Authors: Wenzel Richard G. , Sarvis Carrie A.
Published: June 2004

Study Objective. To evaluate the role of butalbital‐containing products in the management of migraine.

Methods. Qualitative systematic search using MEDLINE (January 1966–November 2001), review of the United States Headache Consortium's evidence‐based guidelines for migraine treatment, and review of other pertinent literature.

Results. Over 28 million people suffer with migraine, yet this illness is less than optimally diagnosed and managed. Between 14% and 36% of diagnosed migraineurs are prescribed butalbital‐containing products, often as initial therapy. However, the only identified controlled trial of these drugs for migraine treatment showed that butalbital‐containing products were inferior to butorphanol. The consortium's guidelines specifically discourage administration of butalbital‐containing products for migraine. In addition, other published literature highlights the frequent adverse consequences of butalbital‐containing products for migraineurs, such as poor migraine control, disability, drug‐induced headaches, and withdrawal symptoms.

Conclusion. Although butalbital‐containing products commonly are prescribed for migraine, no evidence in the literature demonstrates their benefit over other agents or placebo. Drugs with proven migraine efficacy, as listed in the consortium's evidence‐based guidelines, should be prescribed instead.
Drug‐Information Software for Palm Operating System Personal Digital Assistants: Breadth, Clinical Dependability, and Ease of Use
Authors: Enders Shelly J. , Enders Jason M. , Holstad Sheldon G.
Published: June 2004

Study Objective. To examine the breadth, clinical dependability, and ease of use of drug‐information software programs for personal digital assistants that incorporate the Palm operating system.

Design. Prospective evaluation with descriptive analysis.

Methods. Nine drug‐information software programs were evaluated for breadth, clinical dependability, and ease of use, based on responses to 56 questions.

Results. Breadth of information (percentage of questions that could be answered) was 32–75%; LexiComp Platinum was the leader in this category. Clinical dependability (factual completeness) of information was 66.7–100%; LexiComp Platinum led this category as well. MobileMicromedex provided the narrowest breadth of information and the least clinically dependable information. Time to locate an answer to posed questions averaged 17.5 ± 4.98 seconds. The fastest retrieval time was achieved by Davis's Drug Guide for Physicians (12.1 sec). Tarascon's Pharmacopoeia required the fewest viewed PDA screens to locate the requested information (3.3 screens). Cost of programs ranged from free to $129.95. Cost was not related to breadth or clinical dependability.

Conclusions. LexiComp Platinum offered the greatest breadth of information and the most clinically dependable content. MobileMicromedex was the least helpful of these products for answering straightforward drug‐information questions.
Practitioner Acceptance of the Dofetilide Risk‐Management Program
Authors: LaPointe Nancy M. Allen , Kramer Judith M. , Weinfurt Kevin P. , Califf Robert M.
Published: June 2004

Study Objective. To assess the opinions and knowledge retention of practitioners after participation in the dofetilide risk‐management program.

Design. A 21‐item questionnaire.

Setting. A large academic medical center.

Participants. One hundred forty‐six practitioners were given the questionnaire; 91 (62%) completed it.

Measurements and Results. The questionnaire assessed practitioners' opinions of the program and guidelines, preparation time for implementing dofetilide treatment, and retention of facts from the program. Responses were graded on a 5–point Likert scale. Practitioners took a mean of 0.86 ± 0.44 hours to complete the program; physicians took the least time, pharmacists the most. Practitioners agreed the program was necessary but were undecided about whether the guidelines were easily understood or implemented. Nurses answered one of the two knowledge‐retention questions incorrectly significantly more often than physicians or pharmacists. Identification of seven drugs that should not be taken with dofetilide differed significantly (p<0.0001) across groups (mean accuracy score was 41% for nurses, 80% for pharmacists, and 86% for physicians).

Conclusion. This risk‐management program has been well received by practitioners at our institution. We are gathering data to determine whether the program is effective in reducing inappropriate administration of dofetilide.
Asian and Asian‐American College Students' Awareness of Osteoporosis
Authors: Nguyen Diem N. , O'Connell Mary Beth
Published: June 2004

Study Objective. To quantify Asian and Asian‐American college students' knowledge of osteoporosis and preventive health behaviors.

Design. Sixty‐four‐question survey.

Setting. University of Minnesota.

Subjects. One hundred sixty‐eight male and female Asian and Asian‐American students, mean age 21 ± 3.4 years.

Main Results. About half of the students consumed 0–1 servings/day of dietary calcium, 42% consumed 2 cups/day or more of caffeinated beverages, 8% smoked cigarettes, and 61% exercised 2.5 hours/week or less. At least 1 serving/day of phytoestrogen was consumed by 80% of the students. Only 11% of students answered at least 75% of osteoporosis fact questions correctly. Women (p=0.011) and the United States‐born participants (p=0.006) were more apt to change their health behaviors to prevent or treat osteoporosis than men and Asia‐born participants. Thirty‐eight percent of Hmong participants attributed osteoporosis to fate, chance, or luck whereas Vietnamese participants were more likely to attribute osteoporosis to diet. Most participants (63%) did not know whether their culture objected to estrogen replacement therapy, and 42% said menopause was a natural occurrence for which pharmacologic treatment should not be administered.

Conclusions. Many Asian and Asian‐American college students did not practice health behaviors to prevent osteoporosis, and most lacked sufficient knowledge about the condition.
Impact of an Asthma Program on the Quality of Life of Children in an Urban Setting
Authors: Munzenberger Paul J. , Vinuya Ricardo Z.
Published: June 2004

A comprehensive asthma program involving a pharmacist and physician evaluated quality of life (QOL) for children with asthma and the relationship between changes in QOL and traditional outcomes. The program consisted of aggressive medical management and a comprehensive education program. Children were from an inner‐city population who had been referred to a specialist. Twenty of the 29 children enrolled in the program were available for 1‐year follow‐up. Significant improvements were seen in overall QOL scores and in each domain in the instrument, which exceeded the minimal important difference. A strong relationship was not found between changes in QOL total score and changes in asthma questionnaire score, frequency of nocturnal asthma, symptomatic days, and exercise tolerance. Further research is necessary to support these findings.
Severe Prolonged Tacrolimus Overdose with Minimal Consequences
Authors: Hardwick Laura L. , Batiuk Thomas D.
Published: June 2004

A 59‐year‐old man inadvertently received a 10‐fold increase in his twice‐daily oral dose of tacrolimus 1 mg that resulted in trough blood levels above 90 ng/ml for over a week. The patient had end‐stage renal disease secondary to diabetes mellitus and had received a kidney transplant from his daughter 3 months earlier. Despite the numerous adverse effects commonly reported with tacrolimus, such as mild nephrotoxicity, nausea, tremors, and elevated liver enzyme levels, our patient's acute but prolonged overdose resulted in minimal signs and symptoms of toxicity. Nevertheless, education regarding the importance of accurate dosing, close monitoring, potential drug interactions, and the various capsule colors should be provided to all patients who receive tacrolimus, as well as their physicians, nurses, and pharmacists, in order to prevent as many errors as possible.
Inhibition of Warfarin Anticoagulation Associated with Chelation Therapy
Authors: Grebe Heidi Braun , Gregory Philip J.
Published: June 2004

Chelation therapy originally was administered exclusively to patients with heavy metal poisoning. Now some physicians are administering this therapy for numerous conditions, most commonly coronary heart disease. A 64–year‐old man experienced impaired warfarin anticoagulation after undergoing chelation therapy. His international normalized ratio (INR) fell from 2.6 the day before to 1.6 the day after therapy was administered. Whether chelation therapy decreases the effectiveness of warfarin anticoagulation is uncertain. However, because of this potential interaction, clinicians should consider increased INR monitoring in patients undergoing chelation therapy.
Priapism Associated with Two Atypical Antipsychotic Agents
Authors: Reeves Roy R. , Mack James E.
Published: June 2004

Priapism has been associated with many antipsychotic agents, including clozapine, risperidone, and olanzapine. This prolonged, usually painful, penile erection rarely results from the a‐adrenergic blocking action of antipsychotics. A 22‐year‐old African‐American man developed priapism during treatment with risperidone and, on a later occasion, during treatment with ziprasidone. The problem resolved only with substitution of other drugs for these antipsychotics. Certain patients may be more vulnerable than others to this adverse effect. Clinicians must be aware of such complications and use caution when prescribing these drugs.
Promising Microbicide Approach for Prevention of Human Immunodeficiency Virus Transmission Needs More Support
Authors: Idemyor Vincent
Published: June 2004

The human immunodeficiency virus (HIV) is the number one killer worldwide among infectious disease‐causing agents. Because of the speed at which the epidemic has spread, it is crucial for the global community to expand female‐controlled preventive options such as the use of microbicides. Much of microbicide research explores how HIV crosses the mucous membranes of the female genital tract and how the virus can be blocked at that point. The field of microbicides has reached a point where increased political will and expanded investment are required to get products to market in the near future.
Dobutamine Pharmacodynamics During Dobutamine Stress Echocardiography and the Impact of β‐Blocker Withdrawal: A Report from the Women's Ischemic Syndrome Evaluation Study
Authors: Humma Larisa M. , Richardson Heather E. , Lewis Jannet F. , McGorray Susan P. , Pepine Carl J. , Johnson Julie A.
Published: June 2004

Dobutamine Pharmacodynamics During Dobutamine Stress Echocardiography and the Impact of β‐Blocker Withdrawal: A Report from the Women's Ischemic Syndrome Evaluation Study

Study Objectives. To determine the pharmacodynamic parameters of dobutamine during dobutamine stress echocardiography (DSE) and to determine how β‐blocker withdrawal the evening before DSE affects responses to dobutamine during DSE.

Design. Retrospective analysis.

Setting. University medical center.

Patients. One hundred thirty‐six women who had chest pain or other symptoms suggestive of myocardial ischemia and were considered to have a clinical indication for coronary angiography.

Measurements and Main Results. Patients underwent DSE with dobutamine dosages titrated from 5 to 40 μ/kg/minute. The infusion was terminated if the patient reached target heart rate or symptoms developed. Those taking β‐blockers withheld their doses the evening before DSE. Traditional pharmacodynamic modeling revealed a wide range in responses to dobutamine. Data for 62% of patients not taking β‐blockers were described by the Emax (maximum heart rate response to dobutamine) model, whereas data for only 39% of patients taking β‐blockers were best described by this model (p=0.01). Patients taking β‐blockers also had a smaller mean increment in left ventricular ejection fraction (10.8% ± 4.2% vs 14.1% ± 9.3%, p<0.01), a trend toward a higher ED50 (dobutamine dosage rate causing half the maximum heart‐rate response; median 16.8 μg/kg/min, p=0.12) and a lower sigmoidicity factor determining the shape of the curve (median 2.1, p=0.03).

Conclusion. The response to dobutamine exhibits wide interpatient variability, even in the absence of β‐blockade. Nonetheless, in the absence of β‐blockers, in most patients the dobutamine response reaches a plateau by the time the maximum infusion rate (40 μg/kg/min) is reached. Withdrawal of β‐blockers the evening before DSE may be inadequate time for elimination of β‐blocker effect, requiring the addition of atropine to achieve the desired response during DSE.
Differences in Inhaled Fluticasone Bioavailability Between Holding Chambers in Children with Asthma
Authors: Liang Judy , Asmus Michael J. , Hochhaus Günther , Chesrown Sarah , Hendeles Leslie
Published: June 2004

Study Objective. To determine if differences between holding chambers in previous in vitro aerosol studies would agree with the bioavailability of inhaled fluticasone propionate between the same holding chambers in children with asthma.

Design. Double‐blind, randomized, crossover study.

Setting. University of Florida Clinical Research Center.

Patients. Eight children (aged 5–9 yrs) with stable asthma.

Intervention. Under observation, the children inhaled two 110‐μg puffs of fluticasone twice/day through the InspirEase or E‐Z Spacer holding chamber.

Measurements and Main Results. Blood samples were collected at baseline and then at 0.5, 1, 1.5, 2, 4, and 6 hours after the last dose of fluticasone. Primary outcome measures were peak fluticasone steady‐state plasma concentration (Cmax) and area under the fluticasone plasma concentration‐time curve from 0–6 hours (AUC0–6). The fluticasone plasma concentrations were determined by high‐performance liquid chromatography‐mass spectrometric assay. Mean ± SD Cmax from InspirEase (245 ± 77 pg/ml) was 18% higher than that after E‐Z Spacer (199 ± 58 pg/ml, p<0.05). Mean ± SD AUC0–6 from InspirEase (1103 ± 305 pg ·hr−1· ml−1) was 22% higher than that delivered from E‐Z Spacer (863 ± 258 pg · hr−1 · ml−1, p=0.06).

Conclusion. Differences in inhaled fluticasone bioavailability between these holding chambers in children with asthma corroborate differences reported in earlier in vitro aerosol studies.
Collection of Genomic DNA by the Noninvasive Mouthwash Method for Use in Pharmacogenetic Studies
Authors: Andrisin Tara Engeman , Humma Larisa M. , Johnson Julie A.
Published: June 2004

Study Objective. To determine long‐term stability, quantity, and quality of genomic DNA samples collected in buccal cells by the mouthwash method, for use in pharmacogenetic studies.

Design. Prospective analysis.

Setting. University pharmacogenomics center in Florida and medical centers in Puerto Rico and the United States participating in a multicenter international trial.

Subjects. Ten volunteers at the pharmacogenomics center and 201 participants in the ongoing multicenter clinical trial.

Intervention. Stability of genomic DNA was determined by measuring DNA yield from mouthwash samples obtained from six volunteers and stored at room temperature over 90 days and from 201 clinical trial samples that were stored and shipped at room temperature. Whether DNA yield was higher with three 5–ml mouthwash rinses versus one 10–ml rinse was evaluated in four volunteers. Quality of genomic DNA was assessed on 32 randomly selected samples from the six volunteers in the stability study, by determining the success rate of DNA amplification with polymerase chain reaction (PCR) testing and by genotyping.

Measurements and Main Results. For the stability studies, the quantity of genomic DNA decreased over time with storage at room temperature (overall p<0.01), with the largest declines occurring at 60 and 90 days. Median DNA recovery at 30 and 90 days was 59% and 28% of that at baseline, respectively. Mean ± standard deviation, median, and range for recovery of genomic DNA from the 201 samples were 45.2 ± 55 μg, 25.2 μg, and 1–330 μg, respectively. Median recoveries of DNA from the one‐rinse and three‐rinse methods were not statistically significantly different (9.1 vs 10.5 μg). All samples were amplified successfully by PCR and genotyped, indicating quality of the DNA samples.

Conclusion. The mouthwash method for collection of genomic DNA is a simple, inexpensive, and noninvasive method that poses less risk than venipuncture and may be used in a variety of settings. Genomic DNA in mouthwash is stable for prolonged periods at room temperature, and the quantity of DNA recovered from this method is more than sufficient for pharmacogenetic studies. Such an approach should be valuable to pharmacogenetic researchers and others who are conducting genetic research.
Characterizing and Predicting Amphotericin B‐Associated Nephrotoxicity in Bone Marrow or Peripheral Blood Stem Cell Transplant Recipients
Authors: Gubbins Paul O. , Penzak Scott R. , Polston Sabrena , McConnell Scott A. , Anaissie Elias
Published: June 2004

Study Objective. To characterize amphotericin B‐associated nephrotoxicity and to determine the variables associated with it that can be used to identify, a priori, at‐risk patients.

Design. Retrospective analysis.

Setting. University hospital.

Patients. A homogeneous population of 69 recipients of a bone marrow (BMT) or peripheral blood stem cell transplant (PBSCT) with multiple myeloma and who received at least two doses of amphotericin B deoxycholate from January 1, 1992–January 1, 1995.

Intervention. Data on demographics, prior and concomitant nephrotoxic drug therapy, daily laboratory values, and amphotericin B dosing were collected serially from medical and pharmacy records.

Measurements and Main Results. Forward stepwise logistic regression analysis was performed on the data from the first day of therapy to characterize and determine variables related to amphotericin B‐associated nephrotoxicity. Nephrotoxicity occurred in 30 patients (43%) and developed rapidly. Patients who developed nephrotoxicity were similar to those who did not in many aspects associated with their treatment. However, baseline estimated creatinine clearance, cyclosporine therapy, nephrotoxic drug therapy within 30 days of starting amphotericin B, and the number of concomitant nephrotoxic drugs were significant predictors of amphotericin B‐associated nephrotoxicity.

Conclusion. Recipients of a BMT or PBSCT who have multiple myeloma and are receiving cyclosporine or multiple nephrotoxic drugs at the start of amphotericin B therapy should be considered at high risk for developing amphotericin B‐associated nephrotoxicity. Also, because amphotericin B‐associated nephrotoxicity develops rapidly, clinicians should be aware of the rapid changes in serum creatinine and electrolyte levels that can occur.
Aerosolized Ceftazidime for Prevention of Ventilator‐Associated Pneumonia and Drug Effects on the Proinflammatory Response in Critically Ill Trauma Patients
Authors: Wood G. Christopher , Boucher Bradley A. , Croce Martin A. , Hanes Scott D. , Herring Vanessa L. , Fabian Timothy C.
Published: June 2004

Study Objectives. To evaluate the safety and efficacy of aerosolized ceftazidime for prevention of ventilator‐associated pneumonia (VAP) and to evaluate the effects of the drug on the proinflammatory response.

Design. Prospective, randomized, double‐blind, placebo‐controlled clinical trial.

Setting. University teaching hospital.

Patients. Forty critically ill trauma patients at high risk for VAP.

Intervention. Within 48 hours of admission to the intensive care unit (ICU), patients were randomly assigned to receive aerosolized ceftazidime 250 mg every 12 hours or placebo (normal saline) for up to 7 days. Bronchoalveolar concentrations of tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β, IL‐6, and IL‐8 were determined at baseline and the end of therapy (days 4–7).

Measurements and Main Results. The frequency of VAP in patients receiving aerosolized ceftazidime was 73% lower than that in patients receiving placebo at ICU day 14 (15% vs 55%, p=0.021), and 54% lower for the entire ICU stay (30% vs 65%, p=0.022). No clinically significant changes in bacterial culture and sensitivity patterns were observed. No adverse events from aerosolized ceftazidime were reported. Pulmonary TNF‐α, IL‐1β, and IL‐8 concentrations were attenuated in the ceftazidime group compared with those in the placebo group (p<0.001, p=0.02, and p=0.003). The frequency of VAP was related directly to changes in TNF‐α and IL‐1β (p<0.001, p=0.02).

Conclusions. Aerosolized ceftazidime decreased the frequency of VAP in critically ill trauma patients, without adversely affecting ICU flora. Aerosolized ceftazidime also may attenuate the proinflammatory response in the lung.
Trimethoprim‐Sulfamethoxazole Activity and Pharmacodynamics against Glycopeptide‐Intermediate Staphylococcus aureus
Authors: Close Sandy J. , McBurney Christopher R. , Garvin Cory G. , Chen David C. , Martin Steven J.
Published: June 2004

Study Objective. To determine the activity of trimethoprim‐sulfamethoxazole (TMP‐SMX) against glycopeptide‐intermediate Staphylococcus aureus (GISA).

Design. In vitro study.

Setting. University laboratory.

Measurements and Main Results. Minimum inhibitory concentrations (MICs) of TMP‐SMX were determined for three GISA strains. Time‐kill assays were conducted at 1 x MIC and at simulated peak serum concentrations (Cmax). Two dosing regimens of TMP‐SMX were investigated: TMP‐SMX 8 mg (TMP)/kg/day and TMP‐SMX 15 mg/kg/day, each divided into two doses/day. Both dosages were studied against each strain in a two‐compartment in vitro model to determine concentration‐related activity. All isolates were susceptible to TMP‐SMX. In time‐kill studies at 1 x MIC, TMP‐SMX was bacteriostatic against all isolates and bactericidal against two of three strains at simulated Cmax. The 15–mg/kg/day (divided‐dose) regimen provided the best overall reduction in colony‐forming units/ml.

Conclusion. All GISA strains were susceptible to TMP‐SMX. In addition, it appears that TMP‐SMX may have concentration‐dependent antibacterial activity against these organisms. As an option in the management of GISA infection, TMP‐SMX merits further study.
Cost/Death Averted with Venous Thromboembolism Prophylaxis in Patients Undergoing Total Knee Replacement or Knee Arthroplasty
Authors: Nerurkar Ms. Jayanti , Wade William E. , Martin Bradley C.
Published: June 2004

Study Objective. To compare the cost‐effectiveness of warfarin or enoxaparin with no prophylaxis for prevention of venous thromboembolism in patients undergoing total knee replacement (TKR) or knee arthroplasty.

Design. Literature search and retrospective database analysis.

Patients. Cohort of 42,692 patients over 40 years old who underwent TKR or knee arthroplasty, with a subsequent length of stay of at least 1 day, and who did not die postoperatively.

Measurements and Main Results. Both warfarin and enoxaparin were superior to no prophylaxis with regard to costs and clinical outcomes. Enoxaparin was associated with medical charges of $26,455/patient and prevented 194 deaths/10,000 patients. Warfarin was associated with medical charges of $27,360/patient and prevented 124 deaths/10,000 patients.

Conclusions. A wide range of model estimates and assumptions identify enoxaparin as the prophylaxis modality of choice for preventing venous thromboembolism and subsequent clinical complications following total knee replacement surgery.
Differences in Warfarin Dosing Decisions Based on International Normalized Ratio Measurements with Two Point‐of‐Care Testing Devices and a Reference Laboratory Measurement
Authors: Shermock Kenneth M. , Bragg Lee , Connor Jason T. , Fink Jodie , Mazzoli Georgann , Kottke‐Marchant Kandice
Published: June 2004

Study Objectives. To assess the accuracy of warfarin dosing decisions and the degree of numeric bias between two point‐of‐care devices using a local reference laboratory's international normalized ratio (INR) as the standard measure, and to determine the relationship between dosing decisions and INR values obtained with the pointof‐care devices.

Design. Prospective study.

Setting. Outpatient anticoagulation clinic.

Subjects. Two hundred two patients taking oral warfarin and 10 control subjects.

Interventions. For the two point‐of‐care devices, AvoSure and ProTime, the finger‐stick method was used to collect capillary blood samples in each subject. At the same visit, one venous blood sample was collected from each subject for the laboratory analysis.

Measurements and Main Results. Dosing agreement was assessed as the proportion of agreement between each device and the laboratory in terms of maintenance dosage adjustments (increase, decrease, or no change). The level of agreement between each device and the laboratory was evaluated by dosing agreement analysis, bias analysis, and concordance coefficient analysis. In the dosing agreement analysis, 78% of INR values from the AvoSure device would have resulted in the same dosing decision as that with the laboratory INR values compared with 66% from the ProTime device (p<0.001). The mean bias for the ProTime device (0.5 ± 0.4 INR units) was significantly higher (p=0.005) than that for the AvoSure device (0.4 ± 0.5 INR units). The ProTime device overestimated low INR values to a greater extent than did the AvoSure device. Concordance between the laboratory measurement and each device was similar (pc = 0.82 for ProTime, pc = 0.76 for AvoSure).

Conclusions. Assessing dosing decisions yielded distinct, useful clinical information. The AvoSure device is associated with less systematic bias and a higher degree of clinical agreement with our reference laboratory measurement than those of the ProTime device.