Pharmacokinetics of morphine in encephalopathic neonates treated with therapeutic hypothermia

Objective Morphine is a commonly used drug in encephalopathic neonates treated with therapeutic hypothermia after perinatal asphyxia. Pharmacokinetics and optimal dosing of morphine in thi

Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO): Study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)

Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age 65 36 weeks and a birth weight 65 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration: NCT03162653, www.ClinicalTrials.gov, May 22, 2017

Evaluation of a system-specific function to describe the pharmacokinetics of benzylpenicillin in term neonates undergoing moderate hypothermia

The pharmacokinetic (PK) properties of intravenous (i.v.) benzylpenicillin in term neonates undergoing moderate hypothermia after perinatal asphyxia were evaluated, as they have been unknown until now. A system-specific modeling approach was applied, in which our recently developed covariate model describing developmental and temperature-induced changes in amoxicillin clearance (CL) in the same patient study population was incorporated into a population PK model of benzylpenicillin with a priori birthweight (BW)-based allometric scaling. Pediatric population covariate models describing the developmental changes in drug elimination may constitute system-specific information and may therefore be incorporated into PK models of drugs cleared through the same pathway. The performance of this system-specific model was compared to that of a reference model. Furthermore, Monte-Carlo simulations were performed to evaluate the optimal dose. The systemspecific model performed as well as the reference model. Significant correlations were found between CL and postnatal age (PNA), gestational age (GA), body temperature (TEMP), urine output (UO; system-specific model), and multiorgan failure (reference model). For a typical patient with a GA of 40 weeks, BW of 3, 000 g, PNA of 2 days (TEMP, 33.5°C), and normal UO (2 ml/kg/h), benzylpenicillin CL was 0.48 liter/h (interindividual variability [IIV] of 49%) and the volume of distribution of the central compartment was 0.62 liter/kg (IIV of 53%) in the system-specific model. Based on simulations, we advise a benzylpenicillin i.v. dose regimen of 75, 000 IU/kg/day every 8 h (q8h), 150, 000 IU/kg/day q8h, and 200, 000 IU/kg/day q6h for patients with GAs of 36 to 37 weeks, 38 to 41 weeks, and ≥42 weeks, respectively. Thesystem-specific model may be used for other drugs cleared through the same pathway accelerating model development

No association between glucocorticoid receptor polymorphisms and long-term respiratory outcome after very preterm birth

Developmen

Gender differences in respiratory symptoms in 19-year-old adults born preterm

Objective: To study the prevalence of respiratory and atopic symptoms in (young) adults born prematurely, differences between those who did and did not develop Bronchopulmonary Disease (BPD) at neonatal age and differences in respiratory health between males and females. Methods: Design: Prospective cohort study. Setting: Nation wide follow-up study, the Netherlands. Participants: 690 adults (19 year old) born with a gestational age below 32 completed weeks and/or with a birth weight less than 1500g. Controls were Dutch participants of the European Community Respiratory Health Survey (ECRHS). Main outcome measures: Presence of wheeze, shortness of breath, asthma, hay fever and eczema using the ECRHS-questionnaire

Ten-year quality assurance of the nationwide hearing screening programme in Dutch neonatal intensive care units

Aim: To evaluate 10-year quality assurance of newborn hearing screening (NHS) in Dutch neonatal intensive care units (NICU). Methods: Results of the two-stage automated auditory brainstem response (AABR) screening and diagnostic examination in NICU graduates were centrally registered between October 1998 and December 2008. This registration facilitates screening, tracking and follow-up after abnormal screening results. Outcome measures are referral rates, prevalence rate of hearing loss and (trends of) coverage rates and timeliness of follow-up. Results: Thirty-two thousand one hundred and two infants have been screened. Referral rates were 9.2% at the first and 26.3% at the second stage. Hearing loss was diagnosed in 728 infants (2.2%). Coverage rates were 98.7% at the first, 92.1% at the second stage, 92.3% for the diagnostic examination and 97.9% for the complete programme. After correction for gestational age, 95.8% of the infants had their first AABR <1 month, 81.8% of the referred infants had their second AABR <6 weeks and 67.1% were diagnosed <3 months. There was a positive trend in referred infants that had their second AABR <6 weeks (p = 0.004) as well as in infants diagnosed <3 months (p < 0.001). Conclusion: The NHS in Dutch NICUs is effective. Timely identification of hearing loss is improving over time. © 2011 The Author(s)/Acta Pædiatrica

Crowdsourcing and digitalization of electoral integrity:a comparative analysis of Kenya, Tanzania and Uganda

Die Mehrzahl der Staaten zählt heute zu den Unterzeichnern globaler Normen zur Durchführung von nationalen Wahlen. Während digitale Partizipationsmöglichkeiten, insbesondere Crowdsourcing, zur Wahlbeobachtung eine zunehmende Vebreitung finden, bestehen noch immer Zweifel bezüglich der angewendeten Formen und Verfahren und ihrer Rolle bei der Beobachtung von Wahlen. Diese Studie analysiert die neuen digitalen Crowdsourcing-Verfahren die bei den Wahlen in Uganda 2011, Kenia 2013 und Tansania 2015 genutzt wurden. Die Studie basiert auf einer most-similar Fallauswahl, primären und sekundären Quellen und halb-strukturierten Interviews sowie Dokumentanalyse. Als analytisches Rahmenwerk dienen die Konzepte des invented und des invited space, der hybriden Wahlbeobachtung und des elektoralen Zyklus. In the contemporary world, most countries are signatories of global norms governing democratic conduct of elections. While digital participatory methods, especially crowdsourcing, are becoming more common in monitoring electoral procedures, there are uncertainties in terms of the modes and methods employed, and its role on mapping electoral incidents. This study analyses emerging digital crowdsourced method and citizen-generated voices in the Ugandan 2011, Kenyan 2013 and Tanzanian 2015 general elections. The study uses most similar systems design, primary and secondary data sources such as semi-structured face-to-face interviews, datasets and document analysis. The concepts of invented and invited spaces, hybrid monitoring and electoral cycle serve as analytical framework in this research.<br