Population Pharmacokinetic Modeling in the Presence of Missing Time-Dependent Covariates: Impact of Body Weight on Pharmacokinetics of Paracetamol in Neonates.

Body weight is the primary covariate in pharmacokinetics of many drugs and dramatically changes during the first weeks of life of neonates. The objective of this study is to determine if missing body weights in preterm and term neonates affect estimates of model parameters and which methods can be used to improve performance of a population pharmacokinetic model of paracetamol. Data for our analysis were obtained from previously published studies on the pharmacokinetics of intravenous paracetamol in neonates.

Extracorporeal Irradiation and Reimplantation of Tumor-bearing Bone Segments Following Diaphyseal Sarcoma Resection at the Tibia.

Background/aim: Reconstruction of diaphyseal tibial sarcomas with extracorporeal irradiated autograft is a rarely applied technique and is analyzed in this study.

Patients And Methods: Eight patients with malignant sarcomas received local treatment by means of a wide resection and reimplantation of an extracorporeally-irradiated autograft. The graft was combined with an ipsilateral vascularized fibula when a full-thickness segment of the tibia had to be resected and no cortex could be preserved (n=5).

Enhanced early prediction of clinically relevant neonatal hyperbilirubinemia with machine learning.

Background: Machine learning models may enhance the early detection of clinically relevant hyperbilirubinemia based on patient information available in every hospital.

Methods: We conducted a longitudinal study on preterm and term born neonates with serial measurements of total serum bilirubin in the first two weeks of life. An ensemble, that combines a logistic regression with a random forest classifier, was trained to discriminate between the two classes phototherapy treatment vs.

Virtual Periacetabular Osteotomy and Anatomical Measurements.

Objective: To report on a CT scan virtual periacetabular osteotomy (PAO) process to evaluate the potential risk of different PAO cutting planes.

Methods: A total of 123 patients (64 men and 59 women) underwent virtual PAO. We defined two retroacetabular cutting (RC) planes: the RC plane and the RC plane (10 mm posteriorly as compared to the RC plane).

Association between perinatal interventional activity and 2-year outcome of Swiss extremely preterm born infants: a population-based cohort study.

Objectives: To investigate if centre-specific levels of perinatal interventional activity were associated with neonatal and neurodevelopmental outcome at 2 years of age in two separately analysed cohorts of infants: cohort A born at 22-25 and cohort B born at 26-27 gestational weeks, respectively.

Design: Geographically defined, retrospective cohort study.

Setting: All nine level III perinatal centres (neonatal intensive care units and affiliated obstetrical services) in Switzerland.

Exposure to moderate air pollution and associations with lung function at school-age: A birth cohort study.

Background: Adverse effects of higher air pollution levels before and after birth on subsequent lung function are often reported in the literature. We assessed whether low-to-moderate levels of air pollution during preschool-age impact upon lung function at school-age.

Methods: In a prospective birth cohort of 304 healthy term-born infants, 232 (79%) completed lung function at follow-up at six years.

Birth experience in newborn infants is associated with changes in nociceptive sensitivity.

Vaginal birth prepares the fetus for postnatal life. It confers respiratory, cardiovascular and homeostatic advantages to the newborn infant compared with elective cesarean section, and is reported to provide neonatal analgesia. We hypothesize that infants born by vaginal delivery will show lower noxious-evoked brain activity a few hours after birth compared to those born by elective cesarean section.

Biallelic pathogenic variants in the lanosterol synthase gene LSS involved in the cholesterol biosynthesis cause alopecia with intellectual disability, a rare recessive neuroectodermal syndrome.

Purpose: Lanosterol synthase (LSS) gene was initially described in families with extensive congenital cataracts. Recently, a study has highlighted LSS associated with hypotrichosis simplex. We expanded the phenotypic spectrum of LSS to a recessive neuroectodermal syndrome formerly named alopecia with mental retardation (APMR) syndrome.

Association of long-term exposure to traffic-related PM with heart rate variability and heart rate dynamics in healthy subjects.

Background: Epidemiological evidence on the influence of long-term exposure to traffic-related particulate matter (TPM) on heart rate variability (HRV) is weak.

Objective: To evaluate the association of long-term exposure (10 years) with TPM on the regulation of the autonomic cardiovascular system and heart rate dynamics (HRD) in an aging general population, as well as potential modifying effects by the a priori selected factors sex, smoking status, obesity, and gene variation in selected glutathione S-transferases (GSTs).

Methods: We analyzed data from 1593 SAPALDIA cohort participants aged ≥ 50 years.

The influence of gestational age in the psychometric testing of the Bernese Pain Scale for Neonates.

Background: Assessing pain in neonates is challenging because full-term and preterm neonates of different gestational ages (GAs) have widely varied reactions to pain. We validated the Bernese Pain Scale for Neonates (BPSN) by testing its use among a large sample of neonates that represented all GAs.

Methods: In this prospective multisite validation study, we assessed 154 neonates between 24 2/7 and 41 4/7 weeks GA, based on the results of 1-5 capillary heel sticks in their first 14 days of life.

Target-Mediated Drug Disposition Model for Bispecific Antibodies: Properties, Approximation, and Optimal Dosing Strategy.

Bispecific antibodies (BsAbs) bind to two different targets, and create two binary and one ternary complex (TC). These molecules have shown promise as immuno-oncology drugs, and the TC is considered the pharmacologically active species that drives their pharmacodynamic effect. Here, we have presented a general target-mediated drug disposition (TMDD) model for these BsAbs, which bind to two different targets on different cell membranes.

Reliability and predictive validity of the Standardized Infant NeuroDevelopmental Assessment neurological scale.

Aim: To assess reliability and predictive validity of the neurological scale of the Standardized Infant NeuroDevelopmental Assessment (SINDA), a recently developed assessment for infants aged 6 weeks to 12 months.

Method: To assess reliability, three assessors independently rated video-recorded neurological assessments of 24 infants twice. Item difficulty and discrimination were determined.

Aggressive leukemia driven by MLL-AF9.

We recently showed that cellular origin impacts the aggressiveness and the phenotype of acute myeloid leukemia (AML). Direct induction of the MLL-AF9 fusion in various hematopoietic compartments using a doxycycline (DOX) regulated mouse model (iMLL-AF9) led to an invasive chemoresistant AML expressing several genes known to be involved in epithelial to mesenchymal transition (EMT) in solid cancers. Many of these genes play important roles in migration and invasion and are significantly associated with poor overall survival in AML patients.

Neighbourhood child population density as a proxy measure for exposure to respiratory infections in the first year of life: A validation study.

Background: Assessing exposure to infections in early childhood is of interest in many epidemiological investigations. Because exposure to infections is difficult to measure directly, epidemiological studies have used surrogate measures available from routine data such as birth order and population density. However, the association between population density and exposure to infections is unclear.

Respiratory rate in infants with cystic fibrosis throughout the first year of life and association with lung clearance index measured shortly after birth.

Background: Lung impairment in cystic fibrosis (CF) starts in infancy. However, tools to monitor early lung disease are limited. Respiratory rate (RR) as a key vital sign is easy to assess during sleep and is elevated during acute respiratory disease.

Burden of treatment in the face of childhood cancer: A quantitative study using medical records of deceased children.

Lived experiences of childhood cancer patients and their families have been described as interrupted and as a loss of normal life. Apart from symptoms due to the cancer disease, families continuously experience burden of treatment. Since coping capacities are unique to each individual, we captured variables that offer objective measures of treatment burden, with a particular focus on the disruptive effects of treatment on families' lives.

CPAP to diagnose laryngeal clefts by flexible endoscopy in infants.

Background: Laryngeal clefts (LC) are uncommon but important causes of stridor in infants. Direct laryngoscopy is the recommended method for the detection of LC because LC may be missed by flexible endoscopy. As laryngomalacia by far outnumbers any other cause of stridor in this age group flexible bronchoscopy is usually the preferred method for the evaluation of significant infantile stridor.

Personalized weight change prediction in the first week of life.

Background & Aims: Almost all neonates show physiological weight loss and consecutive weight gain after birth. The resulting weight change profiles are highly variable as they depend on multiple neonatal and maternal factors. This limits the value of weight nomograms for the early identification of neonates at risk for excessive weight loss and related morbidities.

Neurofilament as Neuronal Injury Blood Marker in Preeclampsia.

Preeclampsia has been shown to be associated with changes in cerebral structure and cognitive function later in life. Nf (neurofilaments) are specific scaffolding proteins of neurons, and their quantification in serum has been proposed as a biomarker for neuroaxonal injury. We performed a prospective, longitudinal, single-center study at the University Hospital of Basel to determine serum Nf concentrations in pregnant women with singleton pregnancies and with high risk of preeclampsia or with early signs of preeclampsia.

Beta-blockers for prevention and treatment of retinopathy of prematurity in preterm infants.

Background: Retinopathy of prematurity (ROP) is a vision-threatening disease of preterm neonates. The use of beta-adrenergic blocking agents (beta-blockers), which modulate the vasoproliferative retinal process, may reduce the progression of ROP or even reverse established ROP.

Objectives: To determine the effect of beta-blockers on short-term structural outcomes, long-term functional outcomes, and the need for additional treatment, when used either as prophylaxis in preterm infants without ROP, stage 1 ROP (zone I), or stage 2 ROP (zone II) without plus disease or as treatment in preterm infants with at least prethreshold ROP.

Controlling pertussis: how can we do it? A focus on immunization.

Pertussis is a highly contagious disease of the respiratory tract which is caused by the bacterium Bordetella pertussis and is most severe in those <1 year of age. A vaccine against pertussis, introduced in the 1950's, led to a significant decrease in incidence of the disease, but recent increases in outbreaks have been attributed to insufficient vaccine uptake, suboptimal protection conferred by vaccines, and waning immunity after immunization. Areas covered: In this review we discuss the major challenges for controlling pertussis, and what we believe the best strategies are to overcome these challenges, focusing on immunization against pertussis in Europe, but with recommendations that are relevant worldwide.

Palliative care in Swiss pediatric oncology settings: a retrospective analysis of medical records.

Purpose: This study examined the provision of palliative care and related decision-making in Swiss pediatric oncology settings. The aim was to determine if and when children who died from cancer received palliative care, whether there were differences by cancer diagnosis, and inclusion of children in decision-making regarding palliative care.

Methods: Using a standardized data extraction form, a retrospective review of medical records of deceased pediatric patients was conducted.