Explore the vast range of titles available.

The defined daily dose (DDD) as defined by the World Health Organization (WHO) has been the most frequently used unit of measurement to measure antibiotic use. However, measuring antibiotic use in paediatrics is a problem as the WHO DDD methodology is not applicable in children (aged >1 month) due to the large variation in body weight within this population. Based on the narrow range of body weights in the neonatal population, we therefore aimed to develop a set of neonatal DDDs for antibiotics. Eight well-respected (inter)national sources for dosage recommendations of antibiotics in children and neonates were consulted for the assumed maintenance dose of the ten most frequently used antibiotics in neonatal intensive care units in its main indication for neonates. A set of neonatal DDDs for ten commonly used antibiotics in neonates based on an assumed neonatal weight of 2 kg was proposed. Primarily in children DDDs are not applicable to quantify antibiotic use since there is large variation in body weight. In the neonatal population, however, based on its narrow range of body weights and when access to patient level data is not available, neonatal DDDs can be used as a unit of measurement.

Background and Objectives Therapeutic hypothermia can influence the pharmacokinetics and pharmacodynamics of drugs, the discipline which is called thermopharmacology. We studied the effect of therapeutic hypothermia on the pharmacokinetics of phenobarbital in asphyxiated neonates, and the clinical efficacy and the effect of phenobarbital on the continuous amplitude-integrated electroencephalography (aEEG) in a prospective study. Patients and Methods Data were obtained from the prospective SHIVER study, performed in two of the ten Dutch level III neonatal intensive care units. Phenobarbital data were collected between 2008 and 2010. Newborns were eligible for inclusion if they had a gestational age of at least 36 weeks and presented with perinatal asphyxia and encephalopathy. According to protocol in both hospitals an intravenous (repeated) loading dose of phenobarbital 20 mg/kg divided in 1–2 doses was administered if seizures occurred or were suspected before or during the hypothermic phase. Phenobarbital plasma concentrations were measured in plasma using a fluorescence polarization immunoassay. aEEG was monitored continuously. Results and Conclusion A one-compartmental population pharmacokinetic/pharmacodynamic model was developed using a multi-level Markov transition model. No (clinically relevant) effect of moderate therapeutic hypothermia on phenobarbital pharmacokinetics could be identified. The observed responsiveness was 66 %. While we still advise an initial loading dose of 20 mg/kg, clinicians should not be reluctant to administer an additional dose of 10–20 mg/kg. An additional dose should be given before switching to a second-line anticonvulsant drug. Based on our pharmacokinetic/pharmacodynamic model, administration of phenobarbital under hypothermia seems to reduce the transition rate from a continuous normal voltage (CNV) to discontinuous normal voltage aEEG background level in hypothermic asphyxiated newborns, which may be attributed to the additional neuroprotection of phenobarbital in infants with a CNV pattern.

Objective Liquid medicines are easy to swallow. However, they may have disadvantages, such as a bad taste or refrigerated storage conditions. These disadvantages may be avoided by the use of oral solid medicines, such as powders or tablets. The aim of this study was to investigate the acceptability of and preference among four oral formulations in domiciliary infants and preschool children in The Netherlands. Methods Parents administered four oral placebo dosage forms that were aimed at a neutral taste, at home, to their child (1–4 years of age) twice on one day following a randomised cross-over design: small (4 mm) tablet, powder, suspension and syrup. They were asked to report the child's acceptability by a score on a 10 cm visual analogue scale (VAS score) and by the result of the intake. At the end of the study, they were asked to report the preference of the child and themselves. Results 183 children were included and 148 children were evaluated. The data revealed a period/cross-over effect. The estimate of the mean VAS score was significantly higher for the tablet than for the suspension (tablet 9.39/9.01; powder 8.84/8.20, suspension 8.26/7.90, syrup 8.35/8.19; data day 1/all days). The estimate of the mean number of intakes fully swallowed was significantly higher for the tablet than for the other formulations (all p values <0.05). Children and parents preferred the tablet and syrup over the suspension and the suspension over the powder (all p values <0.05). Conclusions All formulations were well accepted. The tablets were the best accepted formulation; the tablets and syrup the most preferred. Trial Registration number ISRCTN63138435.

Objective Perinatal hypoxia-induced free radical formation is an important cause of hypoxic-ischaemic encephalopathy and subsequent neurodevelopmental disabilities. Allopurinol reduces the formation of free radicals, which potentially limits hypoxia-induced brain damage. We investigated placental transfer and safety of allopurinol after maternal allopurinol treatment during labour to evaluate its potential role as a neuroprotective agent in suspected fetal hypoxia. Design We used data from a randomised, double-blind multicentre trial comparing maternal allopurinol versus placebo in case of imminent fetal hypoxia (NCT00189007). Patients We studied 58 women in labour at term, with suspected fetal hypoxia prompting immediate delivery, in the intervention arm of the study. Setting Delivery rooms of 11 Dutch hospitals. Intervention 500 mg allopurinol, intravenously to the mother, immediately prior to delivery. Main outcome measures Drug disposition (maternal plasma concentrations, cord blood concentrations) and drug safety (maternal and fetal adverse events). Results Within 5 min after the end of maternal allopurinol infusion, target plasma concentrations of allopurinol of ≥2 mg/L were present in cord blood. Of all analysed cord blood samples, 95% (52/55) had a target allopurinol plasma concentration at the moment of delivery. No adverse events were observed in the neonates. Two mothers had a red and/or painful arm during infusion. Conclusions A dose of 500 mg intravenous allopurinol rapidly crosses the placenta and provides target concentrations in 95% of the fetuses at the moment of delivery, which makes it potentially useful as a neuroprotective agent in perinatology with very little side effects. Trial registration The study is registered in the Dutch Trial Register (NTR1383) and the Clinical Trials protocol registration system (NCT00189007).

Background Incorrect dosing is the most frequent prescribing error in neonatology, with antibiotics being the most frequently prescribed medicines. Computer physician order entry and clinical decision support systems can create consistency contributing to a reduction of medication errors. Although evidence-based dosing recommendations should be included in such systems, the evidence is not always available and subsequently, dosing recommendations mentioned in guidelines and textbooks are often based on expert opinion. Objective To compare dosage recommendations for antibiotics in neonates with sepsis provided by eight commonly used and well-established international reference sources. Setting An expert team from our Dutch tertiary care neonatal intensive care unit selected eight well-established international reference sources. Method Daily doses of the seven most frequently used antibiotics in the treatment of neonatal sepsis, classified by categories for birth weight and gestational age, were identified from eight well-respected reference sources in neonatology/pediatric infectious diseases. Main outcome measure Standardized average daily dosage. Results A substantial variation in dosage recommendations of antibiotics for neonatal sepsis between the reference sources was shown. Dosage recommendations of ampicillin, ceftazidime, meropenem and vancomycin varied more than recommendations for benzylpenicillin, cefotaxime and gentamicin. One reference source showed a larger variation in dosage recommendations in comparison to the average recommended daily dosage, compared to the other reference sources. Conclusion Antibiotic dosage recommendations for neonates with sepsis can be derived from important reference sources and guidelines. Further exploration to overcome variation in dosage recommendations is necessary to obtain standardized dosage regimens.

Objective To examine the frequency, nature and determinants of clinical pharmacy interventions in paediatric electronic prescriptions. Design Prospective cohort with nested case–control study. Setting Tertiary children's hospital, The Netherlands. Patients Patients 0–18 years with at least one drug prescription admitted to hospital between 1 March 2004 and 1 January 2008, excluding patients receiving intensive care. Interventions Electronic medication prescriptions for paediatric inpatients were verified and if necessary interventions were made by the paediatric clinical pharmacy. Prescriptions requiring intervention (cases) were compared with prescriptions not requiring interventions (controls). Main outcome measures Frequency of clinical pharmacy interventions, per 10 000 paediatric electronic prescriptions, and the determinants thereof. Results Interventions were made for 1577 (1.1%) of 138 449 prescriptions. 81% of the interventions concerned correction of a prescription that might have had adverse clinical consequences. Interventions in prescriptions for antibacterial agents for systemic use were made most often. Most corrections concerned wrong doses (45%). 1577 cases were compared with 1983 controls. The risk of interventions was higher for children aged 1 month to 2 years than for 12–18-year-olds (OR=1.97 (95% CI 1.63 to 2.38)). The risk for ‘free-text’ prescriptions was five times higher than for ‘standardised structured template’ prescriptions. No differences were found between day, evening and night shift prescriptions. Significantly more interventions were made in the oral dosage form (OR=1.63 (95% CI 1.41 to 1.88)) and administration route (OR=1.80 (95% CI 1.55 to 2.09)) than for other reasons. Conclusions Paediatric prescribing errors occur frequently and are not completely prevented by electronic prescribing systems. This study provides information for improvements in electronic prescribing for paediatric patients. Incorporating tailored solutions, such as minimised free-text entry, certain obligatory fields and integrated dose checking and indications, can improve the quality and efficiency of electronic prescribing in paediatrics.

Objective: To investigate whether postnatal allopurinol would reduce free radical induced reperfusion/reoxygenation injury of the brain in severely asphyxiated neonates. Method: In an interim analysis of a randomised, double blind, placebo controlled study, 32 severely asphyxiated infants were given allopurinol or a vehicle within four hours of birth. Results: The analysis showed an unaltered (high) mortality and morbidity in the infants treated with allopurinol. Conclusion: Allopurinol treatment started postnatally was too late to reduce the early reperfusion induced free radical surge. Allopurinol administration to the fetus with (imminent) hypoxia via the mother during labour may be more effective in reducing free radical induced post-asphyxial brain damage.

Objective: To investigate whether postnatal allopurinol would reduce free radical induced reperfusion/reoxygenation injury of the brain in severely asphyxiated neonates. Method: In an interim analysis of a randomised, double blind, placebo controlled study, 32 severely asphyxiated infants were given allopurinol or a vehicle within four hours of birth. Results: The analysis showed an unaltered (high) mortality and morbidity in the infants treated with allopurinol. Conclusion: Allopurinol treatment started postnatally was too late to reduce the early reperfusion induced free radical surge. Allopurinol administration to the fetus with (imminent) hypoxia via the mother during labour may be more effective in reducing free radical induced post-asphyxial brain damage.

Background: Pediatric inpatient settings are known for their high medication error rate. The aim of this study was to investigate whether the Health Care Failure Mode and Effect Analysis (HFMEA) is a valid proactive method to evaluate circumscribed health care processes like prescription up to and including administration of chemotherapy (vincristine) in the pediatric oncology inpatient setting. Methods: A multidisciplinary team consisting of a team leader, pharmacy, nursing and medical staff and a patient’s parent was assembled in a pediatric oncology ward with a computerized physician order entry system. A flow diagram of the process was made and potential failure modes were identified and evaluated using a hazard scoring matrix. Using a decision tree, it was determined for which failure mode recommendations had to be made. Results: The process was divided into three main parts: prescription, processing by the pharmacy, and administration. Fourteen out of 61 failure modes were classified as high risk, 10 of which were sufficiently covered by current protocols. For the other four failure modes, five recommendations were made. Four additional recommendations were made concerning non-high risk failure modes. Most of them were implemented by the hospital management. The whole process took seven meetings and a total of 140 man-hours. Conclusions: The systematic approach of HFMEA by a multidisciplinary team is a useful method for detecting failure modes. A patient or a parent of a patient contributes to the multidisciplinarity of the team.