bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Economic Analysis of Amiodarone versus Placebo for the Prevention of Atrial Fibrillation After Open Heart Surgery
Authors: Reddy Prabashni , Dunn Alisha B. , White C. Michael , Tsikouris James P. , Giri Satyendra , Kluger Jeffrey 
Published: May 2004

Study Objective. To determine if the additional costs of oral amiodarone in patients undergoing open heart surgery would be offset by reductions in the frequency of atrial fibrillation.Design. Piggyback cost analysis of the data from a randomized, double‐blind, placebo‐controlled trial.Setting. Urban academic hospital.Patients. Two hundred twenty elderly patients (≥ 60 yrs old) undergoing open heart surgery.Intervention. Hospital costs of open heart surgery in patients given amiodarone for the prevention of atrial fibrillation and in prespecified subgroups were compared with those for patients given placebo (i.e., standard care with β‐blockers alone).Measurements and Main Results. Total hospital costs incurred were $15,565 ± $9832 and $16,126 ± $8043 in the amiodarone and placebo groups, respectively (p=0.12). General ward, intensive care unit, operating room, pharmacy, and costs in all other departments were similar between the groups (p>0.05 for all comparisons). Because costs were similar but amiodarone was more effective than placebo, amiodarone was cost‐effective compared with placebo. Amiodarone remained cost‐effective compared with placebo regardless of the following subgroup characteristics: rapid or slow loading strategy, no history of atrial fibrillation or heart failure, age older than 70 years, and no tolerance to preoperative β‐blockers. Moreover, in the one‐way sensitivity analysis, the findings remained robust to changes in effectiveness and cost of amiodarone.
Use of Potentially Inappropriate Drugs in Nursing Homes
Authors: Dhall Jyotsna , Larrat E. Paul , Lapane Kate L. 
Published: May 2004

Study Objectives. To examine patterns and determine predictors of inappropriate drug use in nursing homes.Design. Retrospective study.Setting. One thousand four hundred ninety‐two nursing homes in five states.Patients. A total of 44,562 residents admitted to nursing homes over 1 year.Methods. Frequency of discontinuation and initiation of potentially inappropriate drugs over the first 90 days after admission to a nursing home was calculated. Data were collected using the minimum data set.Results. On admission, 33% of residents were receiving at least one potentially inappropriate drug. After 90 days, the drug was discontinued in 16% of these residents. Of those not receiving a potentially inappropriate drug on admission, one was begun in 18%. Demographic factors and number of drugs taken by patients were associated with the use of potentially inappropriate drugs.Conclusions. Use of potentially inappropriate drugs was prevalent on admission and at 90 days after admission. Discontinuation was highest among patients with conditions for which potentially safer therapeutic alternatives existed.
Evaluation of Four Once‐Daily Aminoglycoside Dosing Nomograms
Authors: Wallace Allison Wood , Jones Matthew , Bertino Joseph S. 
Published: May 2004

Study Objective. To evaluate the accuracy of four once‐daily aminoglycoside dosing nomograms in producing the desired gentamicin peak concentration (Cmax) target of 20 μg/ml in patients with varying degrees of renal function.Design. Retrospective analysis using prospectively collected pharmacokinetic data.Setting. Rural teaching hospital.Patients. Ninety patients receiving intravenous gentamicin divided into three groups (30 patients each) determined by estimated renal function: group 1, creatinine clearance (Clcr) 60 ml/minute or greater; group 2, Clcr 40–59 ml/minute; group 3, Clcr) 20–39 ml/minute.Intervention. Serum gentamicin concentrations were collected for a 2–point (two consecutive infusions and one predose and one postdose concentration sampled during steady state) or 3–point (single infusion and one predose and two postdose concentrations at least 1.5 estimated half‐lives apart) pharmacokinetic study for determination of patient‐specific pharmacokinetic parameters (elimination rate constant, volume of distribution at steady state, and clearance) after 30–minute infusions of gentamicin 2.8 ± 1.6 mg/kg.Measurements and Results. The four nomograms evaluated were from Hartford Hospital, Barnes‐Jewish Hospital, University of Rochester, and the Sanford Guide. With a pharmacokinetic analysis program and the patient‐specific pharmacokinetic parameters, CMmax and minimum concentration (Cmin) were determined with use of the recommended doses and dosing intervals of the four nomograms. Also, the gentamicin dose and interval needed to achieve a Cmax) and Cmin) of 20 μg/ml and 0.2 μg/ml, respectively, were determined. Dosing was based on total body weight unless that weight was more than 25% of ideal body weight, in which case, an adjusted body weight was used. In general, the recommended dosages and resultant Cmax) produced by the nomograms were significantly less (p<0.05) than the dosage and Cmax) actually needed to achieve a Cmax): minimum inhibitory concentration (MIC) ratio of 10 or greater for bacteria with an MIC of 2 μg/ml.Conclusion. Once‐daily aminoglycoside dosing using the four nomograms resulted in inaccurate dosing, and because of the large variability in human pharmacokinetics, dosing nomograms such as these should be abandoned in favor of individualizing dosages with therapeutic drug monitoring.
Risk of Acute Liver Injury in Patients with Diabetes
Authors: Huerta Consuelo , Zhao Sean Z. , Rodríguez Luis Alberto García 
Published: May 2004

Study Objectives. To estimate the incidence of acute liver injury in patients with diabetes and compare it with the corresponding incidence in the general population, and to examine the association between occurrence of acute liver injury and administration of antidiabetic drugs in patients with diabetes.Design. Retrospective cohort study.Setting. United Kingdom General Practice Research Database.Patients. A total of 34,328 patients with adult‐onset (type 2) diabetes and a random sample of 50,000 patients with no recorded diagnosis of diabetes; all were aged 20–79 years from 1994–1998 and free of risk factors for hepatic disease.Intervention. Using the United Kingdom General Practice Research Database as our resource, we followed the two cohorts to identify patients with a recorded diagnosis compatible with acute liver injury. Medical records of all patients identified as potentially having liver injury were requested from the general practitioners to validate the diagnosis.Measurement and Main Results. After validation, 27 patients met our definition for having acute liver injury: 14 in the diabetes cohort and 13 in the general population cohort. Overall annual incidence was 14.2 and 8.8/100,000 patient‐years in the diabetes and general population cohorts, respectively. The adjusted relative risk of acute liver injury in the diabetes cohort compared with that of the general population cohort was 1.0 (95% confidence interval [CI] 0.2–3.7). Patients with diabetes taking antidiabetic drugs had a relative risk of 2.8 (95% CI 0.6–12.5) compared with those not taking these drugs.Conclusion. Our findings suggest that diabetes itself does not constitute a major risk for acute liver injury and that a small increased risk could be associated with use of antidiabetic drugs. However, due to the low number of cases detected, the estimates of risk with individual drugs are not conclusive.
Differences in Antimicrobial Drug Exposure in Patients with Various Degrees of Renal Function Based on Recommendations from Dosing References
Authors: Bonapace Charles R. , White Roger L. , Friedrich Lawrence V. , Bosso John A. 
Published: May 2004

Study Objective. To calculate and compare 24–hour area under the unbound drug concentration‐time curves (AUC0.24) of antimicrobials with dosing recommendations from six commonly used dosing references.Intervention. Unbound plasma concentration‐time profiles of 13 antimicrobial agents (4 penicillins, 3 cephalosporins, 2 carbapenems, aztreonam, 3 fluoroquinolones) were simulated at steady state using a one‐compartment open model for a 70–kg adult based on pharmacokinetic parameters obtained from peer‐reviewed literature. Simulations were performed at five levels of creatinine clearance (Clcr).Measurements and Main Results. Differences in AUC0–24 for each antimicrobial agent were noted among the six references at each level of Clcr as well as within references across the range of Clcr. In addition, up to 16–fold and 3–fold ranges in AUC0–24 values were observed for β‐lactams and fluoroquinolones, respectively, in one reference based on dosing recommendations at a single level of Clcr (due to more than one dose and/or dosing interval).Conclusion. Clinicians should be aware of differences among common references when selecting dosages of antimicrobial agents, especially for patients with moderate‐to‐severe renal impairment. (Pharmacotherapy 2002;22(9):1097–1104)
A Review of Methotrexate‐Induced Accelerated Nodulosis
Authors: Patatanian Edna , Thompson Dennis F. 
Published: May 2004

Objective. To review the English‐language literature on methotrexate‐induced accelerated nodulosis, compile case reports of its occurrences, and make recommendations on the clinical management of patients.Methods. A comprehensive search of MEDLINE, TOXLINE, and EMBASE databases was performed, along with a bibliographic search of key articles. Case reports were compiled separately. The Naranjo adverse drug reaction probability scale was used to assess causality.Results. Twenty‐seven case reports of patients with methotrexate‐induced accelerated nodulosis were identified along with one series of 10 patients and one series of 21 patients. Probability assessment for most of the case reports was weak and left room for doubt regarding causality. Most patients were older than 50 years, were positive for rheumatoid factor, and had nodules on their fingers but did not have concurrent vasculitis. Some unusual sites of nodulosis were the larynx, lungs, Achilles tendon, and heart. Of 19 patients given hydroxychloroquine, colchicine, sulfasalazine, azathioprine, or D‐penicillamine, all except two showed regression of the nodules; the response was unknown for one patient.Conclusion. Controversy surrounds the management of patients who develop accelerated nodulosis while receiving methotrexate therapy for rheumatoid arthritis. Our review of these data does not allow definitive conclusions because the available case reports and clinical trials are fragmented and incomplete.
Development and Validation of a Survey to Assess Barriers to Drug Use in Patients with Chronic Heart Failure
Authors: Simpson Scot H. , Johnson Jeffrey A. , Farris Karen B. , Tsuyuki Ross T. 
Published: May 2004

Objective. To report the development of and initial experience with a survey designed to assess patient‐perceived barriers to drug use in ambulatory patients with heart failure.Methods. The Barriers to Medication Use (BMU) survey, developed from previous qualitative work by our group, was administered to 128 consecutive patients attending an outpatient heart failure clinic. The first 42 patients to return the survey were mailed a second survey to evaluate response stability over time. The survey contained 31 questions in five barrier domains (knowledge, previous drug therapy experiences, social support, communication, and relationship with health care professionals). Patients also completed the Minnesota Living with Heart Failure (MLHF) questionnaire and a self‐reported drug use scale. Frequency of drug refills was used to estimate adherence. Reliability and construct validity of the BMU survey were assessed using correlation coefficients.Results. Response rates were 89% and 93% for the first and retest surveys, respectively. The BMU survey showed modest internal consistency in the overall survey and in two of the five barrier domains. Responses to the first and retest surveys showed good stability over time in the overall survey and in four of the five barrier domains. Patients with good adherence reported few barriers; however, the association was not strong (Pearson correlation coefficient r = −0.14, p=0.14). Patients who reported few barriers also reported better MLHF scores (r = 0.42, p<0.001), with the strongest association in the social support domain (r = 0.53; p<0.001). All respondents reported having a good relationship with health care professionals. The most common barriers to drug use were poor support networks and previous adverse reactions.Conclusion. The BMU survey demonstrated reasonable reliability and validity characteristics in this first clinical experience. Despite high adherence, patients still reported barriers that may hinder optimal drug use.
Combination Antiplatelet Therapy: Implications for Pharmacists
Authors: Talbert Robert L. , Spinier Sarah A. , Nappi Jean M. , Bottorff Michael B. 
Published: May 2004

Objectives. To present two case reports of patients who received suboptimal oral antiplatelet therapy and to review recent changes in national guidelines for management of acute coronary syndromes.Data Sources. Personal observation by the authors, and clinical practice guidelines and related clinical trials of the American Heart Association and the American College of Cardiology.Summary. The American College of Cardiology and the American Heart Association revised the guidelines for administration of antiplatelet and anticoagulant therapy in patients with unstable angina and non‐ST‐segment elevation myocardial infarction in March 2002. Two cases observed by the authors illustrate the consequences of suboptimal antiplatelet therapy when a combination of two antiplatelet drugs should have been administered.Conclusion. Evidence from recent randomized controlled trials led to changes in the national guidelines for administration of oral antiplatelet therapy in patients with acute coronary syndromes. Pharmacists should be aware of these changes and counsel patients about appropriate administration of antiplatelet drugs.
Pharmacokinetics of Intravenous and Oral Levofloxacin in Critically Ill Adults in a Medical Intensive Care Unit
Authors: Rebuck Jill A. , Fish Douglas N. , Abraham Edward 
Published: May 2004

Study Objective. To characterize the pharmacokinetic disposition of intravenous and oral levofloxacin in critically ill adults.Design. Prospective, open‐label study.Setting. University teaching hospital.Patients. Thirty critically ill patients in a medical intensive care unit (ICU).Interventions. All patients received levofloxacin as part of their routine medical care. Pharmacokinetic evaluations were performed in 28 patients receiving intravenous levofloxacin. Ten of these patients subsequently were switched to oral levofloxacin and underwent a second pharmacokinetic evaluation during oral therapy.Measurements and Main Results. Mean ± SD levofloxacin half‐life, clearance at steady state, and volume of distribution in all 28 patients were 8.0 ± 1.7 hours, 134 ± 35 ml/minute, and 1.2 ± 0.3 L/kg, respectively. Maximum and minimum serum concentrations (Cmax and Cmin) and area under the serum concentration‐time curve from 0–24 hours (AUC0‐24) in patients receiving levofloxacin 500 mg intravenously were 7.5 ± 0.8 mg/L, 1.0 ± 0.5 mg/L, and 66.1 ± 15.7 mg · hour/L, respectively. Observed Cmax, Cmin, and time at which maximum concentration was achieved after oral doses of levofloxacin 500 mg were 5.5 ± 1.1 mg/L, 0.8 ± 0.4 mg/L, and 1.3 ± 0.4 hours, respectively These values were significantly different (p<0.05) from those observed after intravenous dosing in the same patients; other pharmacokinetic parameters were similar. Statistically significant increases (p<0.05) in Cmax, Cmin, half‐life, and AUC0–24 were found in critically ill patients administered multiple doses of intravenous levofloxacin compared with historical data from healthy volunteers.Conclusions. The dosage regimen of intravenous levofloxacin 500 mg once/day appears adequate for most pathogens found in critically ill patients with normal renal function. Less susceptible pathogens may require an increased daily dose for more optimal therapy. Orally administered levofloxacin appears to be well absorbed in selected ICU patients and has pharmacokinetics similar to those of intravenously administered levofloxacin.
Imatinib Mesylate, the First Molecularly Targeted Gene Suppressor
Authors: Pindolia Vanita K. , Zarowitz Barbara J. 
Published: May 2004

Objective. To review the pharmacology, pharmacokinetics, efficacy, safety and drug‐drug and drug‐food interactions of imatinib and the economic considerations of imatinib in the treatment of chronic myeloid leukemia (CML).Data Sources. Literature accessed through MEDLINE (January 1970‐January 2002), abstracts from the 2001 annual meetings of the American Society of Clinical Oncology and the American Society of Hematology, imatinib product labeling, and additional studies or abstracts identified from the bibliographies of the reviewed literature were used to compile data. Key search terms were allogeneic bone marrow transplant and stem cell transplant, chronic myeloid leukemia, imatinib, interferon, Gleevec, leukemia, gastrointestinal stromal tumors, STI‐571, and tyrosine kinase inhibitors.Findings. Imatinib is a distinctively characteristic drug targeted toward inhibition of tyrosine kinase activity. Imatinib is indicated for the treatment of patients with CML who failed interferon (IFN)‐a therapy and for the treatment of patients with gastrointestinal stromal tumors (GISTs) expressing the tyrosine kinase receptor c‐kit. Imatinib produces positive short‐term hematologic and cytogenetic responses in patients with CML; short‐term positive objective responses have been shown for patients with GISTs. To our knowledge, there are no controlled trials demonstrating long‐term safety, improvement in disease‐related symptoms, or increased survival with imatinib. Serious adverse effects requiring dosage decreases and/or therapy termination are edema, hepatotoxicity, and hematologic toxicity. Imatinib also has been found to inhibit tyrosine kinases involved in the growth of other malignancies. The role of imatinib in tumors that express a tyrosine kinase is constantly evolving with new research results.Conclusions. Imatinib therapy should be limited to patients whose tumor growth is related to a genetically defective tyrosine kinase. In cases of CML, imatinib should be further limited to patients who have tried and failed IFN‐a therapy or who are not candidates for an allogeneic stem cell transplant.
Effect of Renal Impairment on the Pharmacokinetics of a Single Oral Dose of Tibolone 2.5 mg in Early Postmenopausal Women
Authors: Timmer Cees J. , Doorstam Dennis P. 
Published: May 2004

Study Objective. To determine the influence of renal function on the pharmacokinetics of tibolone and its primary metabolites, Δ4‐tibolone, 3α‐hydroxytibolone, and 3β‐hydroxytibolone.Design. Open‐label, single‐center, single‐dose study.Setting. Drug research center, Balatonfüred, Hungary.Subjects. Twenty‐four postmenopausal women aged 45–65 years.Intervention. Subjects were assigned to one of four groups based on their renal function, as assessed by glomerular filtration rate (normal to severely impaired), and received a single dose of tibolone 2.5 mg. Pharmacokinetic parameters of tibolone and its primary metabolites were derived from blood samples taken at predefined intervals for up to 48 hours after tibolone administration. Pharmacokinetic parameters were calculated using standard noncompartmental methods and compared by analysis of covariance.Measurements and Main Results. Pharmacokinetic parameters of tibolone and its primary metabolites were similar in subjects with normal to severely impaired renal function. Pharmacokinetic profiles of tibolone and its metabolites were independent of the degree of renal impairment.Conclusion. Pharmacokinetic parameters of tibolone were not affected by varying degrees of renal function
Effect of a High‐Fat Meal on the Pharmacokinetics of the Des‐F(6)‐Quinolone BMS‐284756
Authors: Gajjar Diptee A. , Sukoneck Samuel C. , Bello Akintunde , Ge Zhiyu , Christopher Lisa , Grasela Dennis M. 
Published: May 2004

Study Objective. To evaluate the effects of a high‐fat meal on the systemic exposure of oral BMS‐284756.Design. Open‐label, randomized, two‐way crossover study.Setting. Clinical research facility.Subjects. Fourteen healthy individuals.Interventions. Participants received two single 400‐mg doses of BMS‐284756, separated by at least 1 week. One dose was given while participants were fasting, and one dose was given within 5 minutes of consumption of a high‐fat meal.Measurements and Main Results. Serial blood samples were collected, and plasma samples were analyzed for BMS‐284756 using a validated liquid chromatography with tandem mass spectrometry detection method. Maximum plasma concentration and area under the plasma concentration‐time curve (AUC) after the high‐fat meal were 19% and 11% lower, respectively, than those in the fasted state. The 90% confidence intervals for the ratios of means (0.71‐0.94 and 0.85‐0.93, respectively) satisfied predefined equivalence criteria. Equivalence of the AUC values for BMS‐284756 in fed and fasted individuals indicates that the presence of food should not affect the efficacy of this drug.Conclusion. Single doses of BMS‐284756 were safe and well tolerated and may be taken without regard to meals.
Hemorrhagic Complications of Enoxaparin and Aspirin in Patients with Kidney Transplants
Authors: Shullo Michael A. , Rose Meredith L. , Vivas Carlos , Jordan Mark L. , Scantlebury Velma P. , Jain Ashok , Corry Robert J. , Fung John J. , McCauley Jerry , Johnston James , Shapiro Ron 
Published: May 2004

Study Objective. To evaluate the frequency of early posttransplant hemorrhagic complications in patients with kidney and kidney‐pancreas transplants who received thromboprophylaxis with enoxaparin and aspirin.Design. Retrospective chart review.Setting. University‐based tertiary care center.Patients. Thirteen patients who had received enoxaparin within 10 days of kidney or kidney‐pancreas transplantation.Intervention. Medical records were reviewed, and data from patients who had received low‐dose aspirin 81 mg once/day and enoxaparin within 10 days of transplantation were collected.Measurements and Main Results. Major bleeding events were defined as intracranial or retroperitoneal bleeding, or a decrease in hemoglobin of greater than 2 g/dl that was confirmed on repeat evaluation. Nine (69%) of the 13 patients had confirmed major bleeding events and required blood transfusions. Six of the nine patients had elevated serum creatinine levels.Conclusion. The combination of enoxaparin and low‐dose aspirin early after kidney or kidney‐pancreas transplantation was associated with a high frequency of hemorrhagic events. Further evaluation is needed to determine the safety of enoxaparin in combination with aspirin after transplantation.