Diclofenac pharmacokinetic meta-analysis and dose recommendations for surgical pain in children aged 1-12 years.

Background: Diclofenac is an effective, opiate-sparing analgesic for acute pain in children, which is commonly used in pediatric surgical units. Recently, a Cochrane review concluded the major knowledge gap in diclofenac use is dosing information. A pharmacokinetic meta-analysis has been undertaken with the aim of recommending a dose for children aged 1-12 years.

Acute liver failure after recommended doses of acetaminophen in patients with myopathies.

Objective: To determine the likelihood that recommended doses of acetaminophen are associated with acute liver failure in patients with myopathies.

Design: Retrospective analysis.

Setting: Level III pediatric intensive care unit.

Invasive ventilation modes in children: a systematic review and meta-analysis.

Introduction: The purpose of the present study was to critically review the existing body of evidence on ventilation modes for infants and children up to the age of 18 years.

Methods: The PubMed and EMBASE databases were searched using the search terms 'artificial respiration', 'instrumentation', 'device', 'devices', 'mode', and 'modes'. The review included only studies comparing two ventilation modes in a randomized controlled study and reporting one of the following outcome measures: length of ventilation (LOV), oxygenation, mortality, chronic lung disease and weaning.

Does minimal access major surgery in the newborn hurt less? An evaluation of cumulative opioid doses.

Background: Minimal access surgery (MAS) in adults is associated with less postoperative pain in comparison to conventional 'open' surgery. It is not known whether this holds true for neonates as well. Less pain would imply that opioid consumption can be reduced, which has a beneficial effect on morbidity.

Predictive Performance of a Recently Developed Population Pharmacokinetic Model for Morphine and its Metabolites in New Datasets of (Preterm) Neonates, Infants and Children.

Background And Objective: Model validation procedures are crucial when models are to be used to develop new dosing algorithms. In this study, the predictive performance of a previously published paediatric population pharmacokinetic model for morphine and its metabolites in children younger than 3 years (original model) is studied in new datasets that were not used to develop the original model.

Methods: Six external datasets including neonates and infants up to 1 year were obtained from four different research centres.

Early developmental assessment of children with major non-cardiac congenital anomalies predicts development at the age of 5 years.

Aim: the aim of this study was to evaluate cognitive and motor development in children with major congenital anomalies and the predictability of development at age 5 years.

Method: a prospective, longitudinal follow-up study was undertaken. The Dutch version of the Bayley Scales of Infant Development - Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) - were administered at the ages of 6, 12, and 24 months.

Systematic evaluation of the descriptive and predictive performance of paediatric morphine population models.

Purpose: A framework for the evaluation of paediatric population models is proposed and applied to two different paediatric population pharmacokinetic models for morphine. One covariate model was based on a systematic covariate analysis, the other on fixed allometric scaling principles.

Methods: The six evaluation criteria in the framework were 1) number of parameters and condition number, 2) numerical diagnostics, 3) prediction-based diagnostics, 4) η-shrinkage, 5) simulation-based diagnostics, 6) diagnostics of individual and population parameter estimates versus covariates, including measurements of bias and precision of the population values compared to the observed individual values.

Predictive performance of a recently developed population pharmacokinetic model for morphine and its metabolites in new datasets of (preterm) neonates, infants and children.

Background And Objective: Model validation procedures are crucial when models are to be used to develop new dosing algorithms. In this study, the predictive performance of a previously published paediatric population pharmacokinetic model for morphine and its metabolites in children younger than 3 years (original model) is studied in new datasets that were not used to develop the original model.

Methods: Six external datasets including neonates and infants up to 1 year were obtained from four different research centres.

Endpoints in pediatric pain studies.

Assessing pain intensity in (preverbal) children is more difficult than in adults. Tools to measure pain are being used as primary endpoints [e.g.

Persistent low microcirculatory vessel density in nonsurvivors of sepsis in pediatric intensive care.

Objective: To investigate the time course and predictive value of microvascular alterations in children with severe sepsis.

Design: Single-center, prospective observational study.

Setting: Intensive care unit of a level III university children's hospital.

The effect of critical illness and inflammation on midazolam therapy in children.

Objective: To determine the effect of inflammation and disease severity on midazolam pharmacokinetics (as surrogate marker of cytochrome 3A activity) and pharmacodynamics in critically ill children.

Design: Analysis of prospectively collected pharmacokinetic and pharmacodynamic data from a midazolam study in critically ill children.

Setting: Pediatric intensive care unit of a university hospital.

Risk factors for chronic lung disease and mortality in newborns with congenital diaphragmatic hernia.

Background: Congenital diaphragmatic hernia (CDH) is associated with a mortality rate of 10-35% in live-born infants. Moreover, CDH survivors have a substantial risk of developing long-term pulmonary sequelae, such as bronchopulmonary dysplasia (BPD).

Objectives: This study aims to evaluate risk factors associated with BPD and mortality in neonates with CDH, with particular focus on the initial ventilation mode.

Pain management in intellectually disabled children: Assessment, treatment, and translational research.

The primary focus of pain research in intellectually disabled individuals is still on pain assessment. Several observational pain assessment scales are available, each with its own characteristics, its own target group and its own validated use. Observational studies report differences in the treatment of intra- and postoperative pain of intellectually disabled children and almost all children with intellectual disability have comorbidities that need to be addressed.

Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe: the CDH EURO Consortium consensus.

Congenital diaphragmatic hernia (CDH) is associated with high mortality and morbidity. To date, there are no standardized protocols for the treatment of infants with this anomaly. However, protocols based on the literature and expert opinion might improve outcome.

Determinants of drug absorption in different ECMO circuits.

Purpose: The aim of this in vitro study was to evaluate potential determinants of drug loss in different ECMO circuits.

Methods: Midazolam, morphine, fentanyl, paracetamol, cefazolin, meropenem and vancomycin were injected into three neonatal roller pump, two paediatric roller pump and two clinically used neonatal roller pump circuits, all with a silicone membrane, and two neonatal centrifugal pump circuits with polypropylene hollow-fibre membranes. Serial blood samples were taken from a post-oxygenator site.

Retinol status of newborn infants is associated with congenital diaphragmatic hernia.

Objective: Genetic analyses in humans suggest a role for retinoid-related genes in the pathogenesis of congenital diaphragmatic hernia (CDH). The goal of this study was to investigate the vitamin A status of mothers and their newborns in association with CDH.

Methods: We conducted a hospital-based, case-control study with 22 case and 34 control mothers and their newborns.

Functional capillary density decreases after the first week of life in term neonates.

Background: Changes in the microcirculation have been recognized to play a crucial role in many disease processes. In premature neonates, functional capillary density (FCD) decreases during the first months of life.

Objectives: The aims of this study were to obtain microcirculatory parameters in term neonates and older children who did not present with compromised respiration or circulation and to determine developmental changes in the microcirculation in young children.

Motor-function and exercise capacity in children with major anatomical congenital anomalies: an evaluation at 5 years of age.

Background: Children with major anatomical congenital anomalies (CA) often need prolonged hospitalization with surgical interventions in the neonatal period and thereafter. Better intensive care treatment has reduced mortality rates, but at the cost of more morbidity.

Aim: To study motor-function and exercise capacity in five-year-old children born with CA, and to determine whether motor-function and exercise capacity differ according to primary diagnosis.

['Acute respiratory distress syndrome' (ARDS) as a serious complication of influenza].

'Acute respiratory distress syndrome' (ARDS) developed as a serious complication of an infection with the influenza virus A (H1N1) ('swine flu') in 3 children: a 15-year-old girl, a 6-year-old boy and a 14-year-old girl. The latter two patients also suffered from septic shock. Intensive ICU treatment, including mechanical ventilation, did not lead to recovery.

Genetics.

For many years karyotyping has been a successful tool to identify chromosome aberrations in congenital malformations. It has proven to be a highly reliable technique for identifying numerical chromosome changes and structural chromosomal rearrangements, such as deletions, duplications, translocations, or inversions. However, karyotyping has limited resolution of 5-10 Mb and depends on the availability of metaphases.

Morphologic changes and methodological issues in the rabbit experimental model for diaphragmatic hernia.

Fetal lung development may be impaired by some congenital anomalies or in utero events. Animal models are used to understand the pathophysiology of these diseases and explore therapeutic strategies. Our group has an interest in the prenatal management of congenital diaphragmatic hernia (CDH).

Prospective longitudinal evaluation of lung function during the first year of life after extracorporeal membrane oxygenation.

Objective: To collect longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation and to evaluate relationships between lung function and perinatal factors. Longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation are lacking.

Design: Prospective longitudinal cohort study.