Evolution of a policy disallowing the use of alternative therapies in a health system.

The evolution of a policy disallowing patients' use of alternative therapies in a health system is described. The pharmacy and therapeutics (P&T) committee at Children's Hospital of Michigan, a part of the Detroit Medical Center (DMC), was asked to review the appropriateness of allowing inpatients to bring in and use alternative therapy products during their hospitalization. Recognizing the interest of consumers in alternative medicines and patients' growing involvement in their own care, the committee drafted a policy that allowed patients to continue taking dietary supplements after being admitted to the hospital. If the physician had no concerns about potential toxicities or drug interactions for a particular product, he or she would write a medication order allowing it to be used. Purchasing and administering the products were deemed the responsibility of the patient or the family. However, many issues concerning supplements remained unresolved, including questions about safety, efficacy, dosing, drug interactions, ethical conflicts, and liability. Ultimately, the P&T committee decided that the potential risks associated with alternative therapies outweighed potential benefits and adopted a policy disallowing the use of alternative therapies by hospitalized patients. The policy was eventually implemented at all eight DMC hospitals. A health system responded to patients' desire to continue their use of alternative therapies during hospitalization by drafting a policy allowing such use. However, concerns related to safety, efficacy, ethics, and liability led to the abandonment of the liberal policy and implementation of a highly restrictive one.

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).

Use of a bisphosphonate (pamidronate) to modulate fracture repair in ovine bone.

Bisphosphonates influence the morphology and mechanical properties of bones in growing rats, but their effects on fracture repair are not well documented. This study tests the hypothesis that bisphosphonates will modulate the remodelling phase of fracture repair, influencing the mechanical properties of healing bone. The effects of a bisphosphonate (pamidronate, Aredia) on the healing of a 3 mm osteotomy gap in the mid-diaphysis of the tibia, under rigid unilateral external fixation, were evaluated using 2 groups of 6 skeletally mature sheep. The repair process was evaluated weekly for 12 weeks using conventional radiographs, dual photon absorptiometry, and fracture stiffness measurements. The animals were then killed and the torsional stiffness and strength of the tibiae measured. More prolific callus formation, with an associated rise in the rate of bone mineral content, was observed in the treated group. There were no differences in in vivo fracture stiffness or postmortem torsional stiffness between the 2 groups, but torsional strength was greater in the treated group. Callus remodelling was reduced but not arrested in the treated group. Bisphosphonates act to reduce callus remodelling, leading to an increased amount of bridging callus and therefore strength. This study indicates that pamidronate has no adverse effects on the restoration of the mechanical integrity of a long bone after fracture.

The tale of a consortium.

Most articles about health service management report successes, but accounts of failure can be no less instructive. Paul Walker describes the failure of a consortium to develop a computer system for the administration of A&E departments and draws some general lessons.

Protein binding characteristics of bumetanide.

The association constants (k) and binding capacities (np) of bumetanide were determined in pooled venous blood obtained from adults, venous cord blood of healthy full-term infants, and critically ill neonates using ultrafiltration. Bumetanide was highly bound to plasma proteins (approximately 97%) in all three populations studied. Two classes of binding sites were identified, a high-affinity, low-capacity site with k and np in the order of 10(3) M-1 and 10(-3) M, respectively, and a low-affinity, high-capacity site with k and np in the order of 10(2) M-1 and 10(-2) M, respectively. Binding capacities were similar between the three groups studied and were larger than the 'presumed' therapeutic concentration following intravenous administration of the drug, which is on the order of 10(-6) M (less than or equal to 0.5 microgram/ml).

Computer-assisted TPN calculations: time savings and improved accuracy associated with use of a minicomputer.

A pediatric TPN computer program, written in Cobol 74 machine language, was developed for use on a minicomputer system. The program calculates the volume of each ingredient needed to prepare a pediatric TPN solution, generates a recipe work card and labels, calculates clinical monitoring information for each patient and develops a clinical monitoring profile for the pharmacist to use in monitoring parenteral nutrition therapy. Use of the program resulted in a significant reduction (71%) in the time needed ot complete TPN calculations. Significant decreases in calculation and labeling errors were also realized.

Evaluation of an empirical dosing schedule for gentamicin in neonates.

The standard gentamicin dosing recommendations for neonates appear to be inappropriate because they fail to consider the influence of neonatal development on gentamicin pharmacokinetics. Recent reports have emphasized that the standard regimens of 2.5 mg/kg q8-12h produce steady-state trough serum concentrations greater than 2 micrograms/ml in up to 91 percent of preterm infants of less than 35 weeks' gestation. A new dosing schedule based on postconceptional age (PCA) was developed to provide a better guideline for initiating and maintaining gentamicin therapy in neonates: PCA greater than 34 weeks, 2.5 mg/kg iv q12h; PCA 28-34 weeks, 2.5 mg/kg iv q16h; PCA less than 28 weeks, 2.5 mg/kg iv q24h. The new dosing schedule reduced the number of neonates with elevated trough concentrations (greater than 2 micrograms/ml) from 68.4 percent to 33-40 percent. Pharmacokinetic parameters for gentamicin in the various PCA groups were determined. Volume of distribution was constant across age groups (0.5 +/- 0.09 L/kg). Elimination rate constants (kel), half-lives, and clearance rates (Cl) ranged from 0.069 +/- 0.02 to 0.14 +/- 0.04 h-1, 10.71 +/- 2.92 to 6.04 +/- 1.24 h, and 0.58 +/- 0.25 to 0.93 +/- 0.24 ml/kg/min, respectively. Significant relationships were found between kel and Cl and patient age and weight; significant correlations were found between actual and estimated (based on PCA and weight) kel and Cl. Variability in kel and Cl estimated was considerable in spite of the correlations. The observed variability stresses again the need for pharmacokinetic monitoring of gentamicin therapy in neonates.

The bilirubin-displacing capacity of bumetanide in critically ill neonates.

Effects of bumetanide on in vitro bilirubin binding to albumin were studied in pooled sera of critically ill neonates using the hydroxybenzeneazobenzoic acid (HBABA) dye binding method and the horseradish peroxidase assay. Mean HBABA dye binding capacity decreased significantly from 63.75 +/- 5.9% in the absence of drug to 50.8 +/- 6.7% and 44.6 +/- 6.3% with concentrations of 0.25 and 50 micrograms/ml, respectively (p less than 0.005). Bumetanide caused an increase in unbound bilirubin concentration at drug concentrations of 0.5-50 micrograms/ml. Bumetanide is a potent displacer of bilirubin and should be used with caution in jaundiced neonates.

Neonatal bilirubin toxicity. A review of kernicterus and the implications of drug-induced bilirubin displacement.

Kernicterus, the primary manifestation of neonatal bilirubin toxicity, remains an important complication of unconjugated hyperbilirubinaemia despite advances made with phototherapy and exchange transfusions. It results from the penetration of bilirubin into neuronal tissues of the CNS with subsequent damage to the mitochondrion. A number of factors may modify or potentiate bilirubin toxicity, including drugs administered to the infant. The importance of drug-bilirubin interactions in the pathogenesis of kernicterus was first realised quite inadvertently in the 1950s, and the potential risk for significant drug-bilirubin interactions has since become an important consideration in neonatal drug therapy. All drugs intended for use in newborn infants should be evaluated for their capacity to displace bilirubin. A number of techniques have been developed which have facilitated investigation of the mechanisms mediating the bilirubin-displacing effects of drugs and the pharmacokinetics of drug-bilirubin interactions. Further, the clinical risk for inducing kernicterus has been investigated for many of the drugs to which neonates may be exposed by direct administration, transplacentally, or through breast milk. This review summarises the available knowledge concerning the physicochemical properties and toxicities of bilirubin, reviews the methodologies used in evaluating drug-bilirubin interactions, and focuses on the mechanisms, pharmacokinetics and clinical significance of the bilirubin displacing effects of antibiotics, anticonvulsants, diuretics, and other important drug classes used in the treatment of neonates.

Compatibility of cefazolin and gentamicin in peritoneal dialysis solutions.

The compatibility of cefazolin and gentamicin in fluid commonly used for continuous ambulatory peritoneal dialysis (CAPD) was studied. Five admixtures containing cefazolin (75 mg/L and 150 mg/L) and gentamicin (8 mg/L), alone and in combination, were prepared in 1.5% dextrose peritoneal dialysis solution. Solutions were stored for 48 hours at 4 degrees C, 26 degrees C, and 37 degrees C; aliquots for drug assay were obtained at 0, 4, 8, 24, and 48 hours. HPLC and immunofluorescent assays were used to determine cefazolin and gentamicin concentrations, respectively. The cefazolin and gentamicin concentration changes over the study period did not reach statistical significance. Maximal cefazolin and gentamicin losses (12 and 7 percent of the initial concentrations, respectively) were observed at 48 hours in solutions stored at 37 degrees C. No significant differences in concentration changes were observed between combination solutions and solutions containing either cefazolin or gentamicin alone. Cefazolin and gentamicin, alone or in combination, are compatible for at least 48 hours in CAPD solutions.

Comparative efficacy study of chewable aspirin and acetaminophen in the antipyresis of children.

Aspirin and acetaminophen are the most widely used antipyretics in pediatrics. Most clinicians believe the drugs to be equally effective, though clinical opinion often suggests that aspirin is more effective at higher temperatures. Fifty-nine outpatients (age range, 2-8 years), presenting with rectal temperatures of 38.8 to 40.5 degrees C, were enrolled in this double-blind trial. The children were stratified by weight and initial temperature. One dose of chewable aspirin or acetaminophen (10-15 mg/kg based on current recommendations for weight) was administered, and rectal temperatures were monitored for three hours. Of the 59 patients enrolled, 46 successfully completed the protocol. Both drugs significantly reduced temperatures in the groups studied. Age did not influence the response of the children to the antipyretic effects of either drug. Aspirin and acetaminophen appeared equally effective when initial temperatures were between 38.8 and 39.9 degrees C. However, when the initial temperature was between 40.0 and 40.5 degrees C, the duration of effect of acetaminophen was shorter than that for aspirin. This suggests that therapeutic differences in the antipyretic activities of aspirin and acetaminophen may exist at higher temperatures.

The prediction of choice in infant feeding: a study of primiparae.

A random sample of 617 white Caucasian primiparae was identified from notifications made to the Leeds Area Health Authority over a 12-month period. Of these, 534 were interviewed regarding personal characteristics, events during pregnancy, and their experience of infant feeding. Significant associations between these factors and the mode of infant feeding initially used are described.From discriminant analysis of two half-populations, weightings were derived for each significantly associated variable, and discriminant scores were calculated for each participant. The distributions of these scores were similar in both half-populations, suggesting that the weightings were stable and thus have potential predictive importance. Further analysis showed that, from all the significant variables, the choice of two (maternal age-group at confinement and age at leaving school) correctly predicted 79 per cent of mothers who will choose to bottle-feed. The potential clinical yield of using these two factors is discussed, and a simple predictive tool for use in everyday practice is presented.

Prediction of duration of breast feeding in primiparas.

A random sample of 617 primiparas was identified from birth notifications over a 12 month period and 534 of these were interviewed four weeks after confinement. Those breast feeding at the time of interview were contacted again at four months and those still breast feeding then were contacted at six and a half months. Duration of breast feeding was found to be significantly associated with five interassociated personal characteristics of the mother and with specific aspects of her knowledge and attitudes regarding breast feeding. In hospital the timing of the first breast feed and difficulties with subsequent feeds, were important indicators; while at home the use of additional formula feeds was associated with a reduced prevalence of breast feeding by 18 weeks. A combination of older maternal age at confinement and older age at leaving school showed a tenfold increase of prevalence rates in breast feeding at 16 weeks between groups of mothers. The use of these two factors alone may thus help doctors, midwives, and health visitors in assessing the risk of premature termination of breast feeding and in planning programmes of preventive care.

Localization of radiolabeled mouse alloantibody in a sarcoma induced by 3-methylcholanthrene.

The distribution of twice-purified I-125-labeled alloantibody, prepared from the serum of strain DBA/2J mice obtained after immunization with strain C3H/HeJ spleen cells, was studied in immunosuppressed DBA/2J mice bearing either an allogeneic C3H/HeJ MCA sarcoma (i.e., one induced by 3-methylcholanthrene) or a syngeneic MCA sarcoma. Radiolabeled antibody was isolated from labeled immune gamma globulin by adsorption onto C3H/HeJ red blood cells and elution from stroma prepared from these cells, followed by Sephadex G-200 gel filtration chromatography. This purified antibody bound specifically in vitro to C3H/HeJ red blood cells. In vivo this antibody localized preferentially in C3H/HeJ MCA sarcomas. An enrichment procedure was developed to increase the yield of radiolabeled alloantibody. The localization of I-131-labeled alloantibody in allogeneic tumor was visualized by external scintigraphy. Control I-131-labeled normal DBA/2J gamma globulin did not show such tumor localization.