Translation and linguistic validation of a disease-specific quality of life measure for cystic fibrosis.

OBJECTIVE: To develop a conceptually and semantically valid English version of a French disease-specific measure of quality of life for children, adolescents, and adults with cystic fibrosis (CF). METHODS: Following a backward and forward translation of the measure, 60 participants, including 20 children, 20 parents, and 20 adolescents/young adults completed the Cystic Fibrosis Questionnaire (CFQ) and a series of cognitive probes evaluating their understanding of the items and response choices. RESULTS: Semantic and conceptual problems with the items were identified and modified for the second set of cognitive interviews. Response distributions across items and ages were adequate, and the predicted associations between disease severity and quality of life were obtained. CONCLUSIONS: The English version of the CFQ appears to be a linguistically valid measure of quality of life for patients with CF. A national validation study is now under way to test the psychometric properties of the measure.

Quality of life as a treatment outcome in patients with cystic fibrosis.

We attempted to determine the responsiveness and validity of the Quality of Well-Being (QWB) scale in 20 consecutive children and adolescents with cystic fibrosis. The QWB score was determined for 6-day periods immediately before and after hospital admission, and at 6- and 12-month follow-up. With the instrument's scale of zero-1, responsiveness was indicated by significant changes in QWB score (0.09), physical (0.019), social (0.021), and symptom-problem complexes (0.04) domains, and all pulmonary function tests from before to after treatment of an acute exacerbation. Only the symptom-problem complex domain significantly changed from after treatment to 6- and 12-month follow-up. Validity was shown by significant correlations between before and after QWB scores and forced vital capacity (r=0.476), residual volume total lung capacity ratio (r=0.452), forced expiratory volume in 1 second (r=0.358), and forced expiratory flow between 25% and 75% of vital capacity (r=0.35).

Severe withdrawal syndrome possibly associated with cessation of a midazolam and fentanyl infusion.

A 40-month-old child was sedated with a fentanyl and midazolam infusion for 7 days. After the drugs were discontinued he became unresponsive and globally aphasic, and had marked thrombocytosis. He was hospitalized for 4 weeks, during which time his motor and cognitive status slowly improved, and had almost returned to baseline at time of discharge. Severe neurologic abnormalities have been reported with midazolam and fentanyl, administered separately or together, and seem to be a consequence of a withdrawal syndrome. Of interest, this patient had a reactive thrombocytosis at the time of onset of the withdrawal syndrome, and his decreased platelet count coincided with the return to normal cognitive and motor status. Based on this experience and other reports, we believe midazolam-fentanyl combination should be administered with caution.

Relationship of ceftazidime pharmacokinetic indices with therapeutic outcome in patients with cystic fibrosis.

In this study we investigated the relationships between ceftazidime pharmacokinetic indices and clinical outcome measurements during acute pulmonary exacerbations in patients with cystic fibrosis. Twenty patients received ceftazidime during the study period. On Days 2, 7 and 14 outcome measurements were assessed. Ceftazidime peaks and troughs were calculated as was the percentage of time of the dosing interval the serum concentration/minimum inhibitory concentration ratio exceeded 8, 4 and 1. There were significant differences between Days 2 and 7 and between Days 2 and 14 for the outcome measurements. There were no significant between-day differences for the pharmacokinetic indices. Significant correlations, involving both within and between study days, existed between the ceftazidime pharmacokinetic indices and the clinical outcome measurements. Further investigation of these relationships is warranted.

Home parenteral antibiotic therapy for patients with cystic fibrosis.

Cystic fibrosis is a genetic disease that affects multiple organ systems. Pulmonary complications associated with it frequently require intense intravenous antibiotic therapy. Home care allows patients to be treated at home, reducing the disruption of family life. New drug administration devices allow the patient increased mobility and independence. With adequate family and nursing support, patients may be able to attend work or school. Reduced hospital stays are good for the patient and cost effective for the hospital. The success of home antibiotic therapy depends on careful selection of the candidate, antibiotic regimen, nursing agency, and home care company. Many patients and families, though motivated, cannot manage the additional stress and time commitment required for home intravenous antibiotic and chest physical therapy. This time commitment may be reduced somewhat by limiting the number of antibiotics and the frequency of their administration.

Pharmacokinetics of gentamicin in neonatal patients supported with extracorporeal membrane oxygenation.

This analysis of gentamicin pharmacokinetics involved 15 neonates supported by extracorporeal membrane oxygenation (ECMO). Two sets of blood samples were obtained from each neonate while supported by ECMO. The mean volume of distribution, elimination half-life, and clearance calculated from the first set of samples were 0.62 liters/kg, 7.6 hours, and 1.17 ml/kg/minute, respectively. Mean values from the second set of samples were 0.61 liters/kg, 7.9 hours and 0.99 ml/kg/minute, respectively. There were no statistical differences (p greater than 0.05) between the pharmacokinetics calculated from the first and second set of samples. A comparison of our results with those of others involving neonates not supported by ECMO failed to demonstrate any major impact of ECMO on the pharmacokinetics of gentamicin.

Evaluation of Ames Seralyzer for the therapeutic drug monitoring of phenobarbital and phenytoin.

Comparison of a reflective photometry assay (Ames Seralyzer) and a fluorescence polarization immunoassay (Abbott TDx) for measuring phenobarbital and phenytoin serum concentration was performed. Routine phenobarbital and phenytoin plasma levels drawn from patients in the pediatric neurology clinic and pediatric intensive care unit were determined in duplicate by the Abbott TDx and Ames Seralyzer systems. A total of 40 samples were assayed. The interday and intraday variability of the Ames system was determined using calibrators of known concentrations (5-25 micrograms/ml). There was significant correlation between the serum phenobarbital or phenytoin concentrations when determined by the Seralyzer and TDx systems. The intraday variability for the measurement of phenytoin when determined by the Seralyzer had coefficients of variation ranging from 2.2 to 8.9%. The interday variability for phenytoin when measured by both the TDx and the Seralyzer correlated well with known calibrators. The utility of the Ames Seralyzer for acute-care facilities, physician offices, and pharmacy satellites is apparent. Based on statistical analysis, the Seralyzer provides accurate phenobarbital and phenytoin serum measurements for clinical use in therapeutic drug monitoring.

A clinical comparison of terbutaline with albuterol administered by metered-dose inhaler.

The effects of albuterol and terbutaline administered by metered-dose inhaler were compared via a randomized crossover design. For 20 previously diagnosed asthmatics, spirometric measurements were determined prior to and at nine times post-dose up to six hours. Patients used each drug for a 7-day test period and recorded the occurrence of side effects. As measured by FEV1 and FEF25-75, both drugs caused a rapid and significant bronchodilation of approximately 4-hour duration. For both drugs, there was little effect on blood pressure and heart rate and reported side effects were minimal. There was no statistically significant difference between drugs in pulmonary response nor in any reported side effect.

Variability of tobramycin pharmacokinetics in cystic fibrosis.

This study determined the extent and impact of tobramycin pharmacokinetic variability in cystic fibrosis patients. Twenty patients were hospitalized twice and the tobramycin half-life, volume of distribution and clearance were determined during Weeks 1 and 2 of both admissions. A difference (P less than 0.05) existed between Weeks 1 and 2 of each admission, but not between admissions, for the clearance and half-life. No difference existed between weeks or admissions for the volume of distribution. No significant correlations existed between weeks within an admission for the half-life and clearance. There was a significant correlation for the volume of distribution between Weeks 1 and 2 of the second admission but not for the first admission. The percents of coefficient of variation and ranges were large. With dosing regimens derived from previously determined factors, "within admission" predicted peaks and troughs would result in 60 and 35% of patients outside the therapeutic range for Admissions 1 and 2, respectively. "Between admission" predictions would result in 65 and 75% of patients outside the therapeutic range. We conclude that considerable variability exists and recommend weekly determinations of serum concentrations and dosing adjustments.

The use of a rapid theophylline assay in the ambulatory setting.

The Seralyzer reflectance photometer was evaluated in three ambulatory settings. Of the total 99 assays in the pediatric general medicine clinic, 47 were below the therapeutic range, and 20 patients were noncompliant. There were 13 low and nine high levels along with 22 noncompliant patients detected from a total of 109 in the allergy clinic. The physician's office documented 43 low and four high levels along with 10 noncompliant patients from 105 assays. The mean time required for Seralyzer results in both the allergy and pediatric general medicine clinic was 13 minutes. Regression analysis of both finger-stick and venipuncture split samples indicated a strong correlation between Seralyzer results and traditional methods of assay (r = 0.94 and 0.99, respectively). The Seralyzer proved accurate, timely, and simple to operate.

Comparison of the Seralyzer and EMIT systems for determination of theophylline concentrations.

A reflectance photometry assay for measurement of serum theophylline concentration was evaluated by comparison with an enzyme-multiplied immunoassay technique (EMIT). The concentration of theophylline in blood samples obtained from patients receiving intravenous theophylline therapy in the pediatric intensive-care unit was measured by both the Seralyzer and the EMIT systems. The interday and intraday variability of each method were also determined by means of calibrators of known concentration (5 to 40 micrograms/mL). There was significant correlation between the serum theophylline concentrations determined by the Seralyzer system and the EMIT system. The overall standard error of the estimate was 2.3 micrograms/mL, but with operator experience this improved to 1.3 micrograms/mL. Intraday variability was 1.2 micrograms/mL for the Seralyzer and 0.7 micrograms/mL for EMIT; the respective values for interday variability were 1.4 micrograms/mL and 0.8 micrograms/mL. The Seralyzer method measures theophylline concentrations with reliability, convenience, and speed. It could be potentially useful in a satellite, clinic, or acute-care pharmacy area.

Individualization of tobramycin dosage in patients with cystic fibrosis.

Tobramycin was administered to 52 patients, ages 2 months to 27 years, with cystic fibrosis during acute exacerbation of Pseudomonas-related pulmonary infection. Elimination pharmacokinetics of tobramycin was characterized for each patient after intravenous administration using a standardized infusion technique. The minimal inhibitory concentration was determined for Pseudomonas strains isolated from 26 of the 52 patients. The pharmacokinetic parameters of individual patient were used to adjust the dose and dosing interval to maintain the serum concentration of tobramycin above the minimal inhibitory concentration for the infecting organism for at least 75% of the dosing interval without exceeding the maximum concentration of 12 micrograms/ml or a minimum concentration of 2.0 micrograms/ml. This resulted in an increase of the mean daily dose of tobramycin to 12 mg/kg from an initial mean dose of 5.5 mg/kg and a reduction of the dosing interval from 8 hours to 4 or 6 hours for patients greater than 1 year of age. Significant differences between the pharmacokinetic profiles of the infants and older patients were observed.

Effect of antipyretics on the length of hospital stay of pediatric patients with bacterial infections.

Antipyretic use in pediatric patients with uncomplicated bacterial infections was characterized, and the effect of such therapy on the length of hospital stay of these patients was studied. Study patients were divided into six groups of 30 patients. Patients with pneumococcal pneumonia, staphylococcal cellulitis, or H. influenzae meningitis receiving at least two antipyretic doses were compared with their counterparts receiving one or no antipyretic doses. Of the total 299 antipyretic doses administered, 284 were acetaminophen. Patients with H. influenzae meningitis received a mean of 4.57 doses per patient, which was significantly greater than the other study groups (p less than 0.05). In contrast, patients with staphylococcal cellulitis received the highest mean dose of 12.51 mg/kg of acetaminophen. There appeared to be a relationship between the admitting temperature and the mean length of hospital stay; higher admitting temperatures were correlated with increased length of stay. Analysis of covariance for the different study groups indicated no significant difference in length of hospital stay (p greater than 0.05).

Pediatric dosing--the pharmacist's dilemma.

Several pediatric dosing rules commonly are published in medical and pharmaceutical texts. However, most authorities do not regard these published dosing rules (e.g., Clark's weight rule) to be responsible approaches to pediatric dosing. This study compares the actual doses administered to patients in a 310-bed, university-affiliated, pediatric hospital with the dose calculated for each patient using Clark's weight rule, Clark's surface area rule, Young's age rule, and Shirkey's dosing recommendations. A t test analysis for paired comparisons revealed that the actual dose administered differed significantly from doses calculated, except for doses calculated using Clark's surface area rule. The dosage deviation range was greatest for Clark's surface area rule. This suggests that Clark's surface area rule is also unreliable. Responsible dosing must involve more than the application of commonly published, pediatric dosing calculation rules. Shirkey's recommendations provided the most reasonable approach to pediatric dosing. However, pharmacists should monitor these patients carefully and recommend dosage adjustments whenever necessary.