bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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 StudyStudy 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.
SLI381 (Adderall XR), a Two‐Component, Extended‐Release Formulation of Mixed Amphetamine Salts: Bioavailability of Three Test Formulations and Comparison of Fasted, Fed, and Sprinkled Administration
Authors: Tulloch Simon J. , Zhang Yuxin , McLean Angus , Wolf Kathleen N. , Mays David A. 
Published: June 2004

Study Objectives. To assess the bioavailability of three test formulations of a single dose of extended‐release Adderall 20‐mg capsules compared with two doses of immediate‐release Adderall 10‐mg tablets, and to assess the bioequivalence of a single 30‐mg dose of the chosen extended‐release Adderall formulation (designated as SLI381) administered in applesauce (sprinkled) and the same dose administered as an intact capsule with or without food.Design. Randomized, open‐label, crossover study.Setting. Clinical research unit.Patients. Forty‐one healthy adults.Interventions. Study A had four treatment sequences: three test formulations (A, B, and C) of a single dose of extended‐release Adderall 20 mg, and two 10‐mg doses of Adderall given 4 hours apart. Study B had three treatment sequences: a single dose of SLI381 30 mg as an intact capsule after overnight fast, an intact capsule after a high‐fat breakfast, and the contents of a capsule sprinkled in 1 tablespoon of applesauce.Measurements and Main Results. The 20‐mg test formulation A had comparable pharmacokinetic profiles and bioequivalence in rate and extent of drug absorption to Adderall 10 mg twice/day for both d‐ and l‐amphetamine. Formulations B and C had statistically significant differences from the reference drug in some pharmacokinetic parameters. A 30‐mg dose of SLI381 showed no significant differences in rate and extent of absorption of d‐ and l‐amphetamine for fasted or sprinkled conditions compared with the high‐fat meal condition.Conclusion. SLI381 20 mg/day is bioequivalent to Adderall 10 mg twice/day. SLI381 30 mg administered in applesauce is bioequivalent in terms of both rate and extent of absorption to the same dose administered as an intact capsule in both fasted and fed states.
Abnormal Movements and Tardive Dyskinesia in Smokers and Nonsmokers with Schizophrenia Genotyped for Cytochrome P450 2D6
Authors: Ellingrod Vicki L. , Schultz Susan K. , Arndt Stephan 
Published: June 2004

Study Objective. To investigate the relationships between cytochrome P450 (CYP) 2D6 genotype, antipsychotic drug exposure, abnormal movements and tardive dyskinesia, and cigarette smoking.Design. Prospective, longitudinal study.Setting. University mental health research center.Patients. Thirty‐seven patients with schizophrenia.Intervention. Patients were genotyped for CYP2D6*1, *3, and *4 alleles, and data were collected on their psychiatric symptoms, cigarette smoking status, and antipsychotic drug exposure. Abnormal movements were measured using the Abnormal Involuntary Movement Scale (AIMS). Presence of tardive dyskinesia was also evaluated.Measurements and Main Results. A linear regression model used the AIMS scores as the dependent variable, and genotype, sex, smoking status, and antipsychotic drug exposure as independent variables. Antipsychotic drug exposure, genotype, and cigarette smoking interaction was significant (p<0.0212) for patients with the CYP2D6*1/*3, *4 genotype. Seventy‐eight percent of smokers with the CYP2D6*1/*3, *4 genotype had tardive dyskinesia compared with 20–33% of patients in other groups.Conclusion. Patients with a CYP2D6*3 or *4 allele may shunt antipsychotic metabolism through other pathways that are induced by cigarette smoke. This induction may result in formation of neurotoxic metabolites, leading to increased AIMS scores and a higher frequency of tardive dyskinesia compared with patients without these alleles.