Theoretical Performance of Nonlinear Mixed-Effect Models Incorporating Saliva as an Alternative Sampling Matrix for Therapeutic Drug Monitoring in Pediatrics: A Simulation Study.

Background: Historically, pharmacokinetic (PK) studies and therapeutic drug monitoring (TDM) have relied on plasma as a sampling matrix. Noninvasive sampling matrices, such as saliva, can reduce the burden on pediatric patients. The variable plasma-saliva relationship can be quantified using population PK models (nonlinear mixed-effect models).

Diagnostic accuracy of the response to the brief tachycardia provoked by standing in children suspected for long QT syndrome.

Background: Adult long QT syndrome (LQTS) patients have inadequate corrected QT interval (QTc) shortening and an abnormal T-wave response to the sudden heart rate acceleration provoked by standing. In adults, this knowledge can be used to aid an LQTS diagnosis and, possibly, for risk stratification. However, data on the diagnostic value of the standing test in children are currently limited.

Postdischarge Recovery after Acute Pediatric Lung Disease Can Be Quantified with Digital Biomarkers.

Background: Pediatric patients admitted for acute lung disease are treated and monitored in the hospital, after which full recovery is achieved at home. Many studies report in-hospital recovery, but little is known regarding the time to full recovery after hospital discharge. Technological innovations have led to increased interest in home-monitoring and digital biomarkers.

Development and Technical Validation of a Smartphone-Based Cry Detection Algorithm.

The duration and frequency of crying of an infant can be indicative of its health. Manual tracking and labeling of crying is laborious, subjective, and sometimes inaccurate. The aim of this study was to develop and technically validate a smartphone-based algorithm able to automatically detect crying.

The influence of chest X-ray results on antibiotic prescription for childhood pneumonia in the emergency department.

The aim of this study is to evaluate the influence of chest X-ray (CXR) results on antibiotic prescription in children suspected of lower respiratory tract infections (RTI) in the emergency department (ED). We performed a secondary analysis of a stepped-wedge, cluster randomized trial of children aged 1 month to 5 years with fever and cough/dyspnoea in 8 EDs in the Netherlands (2016-2018), including a 1-week follow-up. We analysed the observational data of the pre-intervention period, using multivariable logistic regression to evaluate the influence of CXR result on antibiotic prescription.

The impact of lockdown on pediatric ED visits and hospital admissions during the COVID19 pandemic: a multicenter analysis and review of the literature.

The coronavirus disease 2019 pandemic has enormous impact on society and healthcare. Countries imposed lockdowns, which were followed by a reduction in care utilization. The aims of this study were to quantify the effects of lockdown on pediatric care in the Netherlands, to elucidate the cause of the observed reduction in pediatric emergency department (ED) visits and hospital admissions, and to summarize the literature regarding the effects of lockdown on pediatric care worldwide.

Parental assessment of disease severity in febrile children under 5 years of age: a qualitative study.

Objective: To explore how parents judge disease severity of their febrile child and to identify symptoms they associate with serious illness, minor illness or health.

Design: Semistructured interviews were conducted. Interviews were audio taped, transcribed verbatim and analysed thematically.

Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL), defined primarily by developmental delay/intellectual disability, speech delay, postnatal microcephaly, and dysmorphic features, is a syndrome resulting from heterozygous variants in the dosage-sensitive bromodomain PHD finger chromatin remodeler transcription factor BPTF gene. To date, only 11 individuals with NEDDFL due to de novo BPTF variants have been described. To expand the NEDDFL phenotypic spectrum, we describe the clinical features in 25 novel individuals with 20 distinct, clinically relevant variants in BPTF, including four individuals with inherited changes in BPTF.

The Efficacy of Anti-Arrhythmic Drugs in Children With Idiopathic Frequent Symptomatic or Asymptomatic Premature Ventricular Complexes With or Without Asymptomatic Ventricular Tachycardia: a Retrospective Multi-Center Study.

The aim of the study is to compare the efficacy of flecainide, beta-blockers, sotalol, and verapamil in children with frequent PVCs, with or without asymptomatic VT. Frequent premature ventricular complexes (PVCs) and asymptomatic ventricular tachycardia (VT) in children with structurally normal hearts require anti-arrhythmic drug (AAD) therapy depending on the severity of symptoms or ventricular dysfunction; however, data on efficacy in children are scarce. Both symptomatic and asymptomatic children (≥ 1 year and < 18 years of age) with a PVC burden of 5% or more, with or without asymptomatic runs of VT, who had consecutive Holter recordings, were included in this retrospective multi-center study.

Towards remote monitoring in pediatric care and clinical trials-Tolerability, repeatability and reference values of candidate digital endpoints derived from physical activity, heart rate and sleep in healthy children.

Background: Digital devices and wearables allow for the measurement of a wide range of health-related parameters in a non-invasive manner, which may be particularly valuable in pediatrics. Incorporation of such parameters in clinical trials or care as digital endpoint could reduce the burden for children and their parents but requires clinical validation in the target population. This study aims to determine the tolerability, repeatability, and reference values of novel digital endpoints in healthy children.

The Dutch Incidence of Infantile Hypertrophic Pyloric Stenosis and the Influence of Seasons.

Introduction:  Studies report contradicting results on the incidence of infantile hypertrophic pyloric stenosis (IHPS) and its association with seasons. We aim to assess the IHPS incidence in the Netherlands and to determine whether seasonal variation is present in a nationwide cohort.

Materials And Methods:  All infants with IHPS hospitalized in the Netherlands between 2007 and 2017 were included in this retrospective cohort study.

Cost Study of a Cluster Randomized Trial on a Clinical Decision Rule Guiding Antibiotic Treatment in Children With Suspected Lower Respiratory Tract Infections in the Emergency Department.

Background: Children with fever and respiratory symptoms represent a large patient group at the emergency department (ED). A decision rule-based treatment strategy improved targeting of antibiotics in these children in a recent clinical trial. This study aims to evaluate the impact of the decision rule on healthcare and societal costs, and to describe costs of children with suspected lower respiratory tract infections (RTIs) in the ED in general.

Serum hepcidin concentrations in relation to iron status in children with type 1 diabetes.

Chronic low-grade inflammation in type 1 diabetes (T1D) might increase hepcidin synthesis, possibly resulting in functional iron deficiency (FID). We hypothesized that in T1D children with FID, hepcidin concentrations are increased compared to those with normal iron status and those with absolute iron deficiency (AID). We evaluated hepcidin concentrations in T1D children in relation to iron status, and investigated whether hepcidin is useful in assessing FID.

Development of Novel, Value-Based, Digital Endpoints for Clinical Trials: A Structured Approach Toward Fit-for-Purpose Validation.

Novel digital endpoints gathered via wearables, small devices, or algorithms hold great promise for clinical trials. However, implementation has been slow because of a lack of guidelines regarding the validation process of these new measurements. In this paper, we propose a pragmatic approach toward selection and fit-for-purpose validation of digital endpoints.

Interventions with Music in PECTus excavatum treatment (IMPECT trial): a study protocol for a randomised controlled trial investigating the clinical effects of perioperative music interventions.

Introduction: Pectus excavatum repair is associated with substantial postoperative pain, despite the use of epidural analgesia and other analgesic regimens. Perioperative recorded music interventions have been shown to alleviate pain and anxiety in adults, but evidence for children and adolescents is still lacking. This study protocol describes a randomised controlled trial that evaluates the effects of recorded music interventions on postoperative pain relief in children and adolescents after pectus excavatum repair.

Technical validity and usability of a novel smartphone-connected spirometry device for pediatric patients with asthma and cystic fibrosis.

Background: Diagnosis and follow-up of respiratory diseases traditionally rely on pulmonary function tests (PFTs), which are currently performed in hospitals and require trained personnel. Smartphone-connected spirometers, like the Air Next spirometer, have been developed to aid in the home monitoring of patients with pulmonary disease. The aim of this study was to investigate the technical validity and usability of the Air Next spirometer in pediatric patients.

Effect of treatment on cognitive and attention problems in children with narcolepsy type 1.

Study Objectives: To ascertain the presence of cognitive and attention problems in treatment naïve children with narcolepsy type 1 (NT1) and to explore whether children recently diagnosed with NT1 improve with respect to cognition and attention problems 1 year after regular treatment for NT1.

Methods: A total of 15 treatment naïve children (7-15 years) with recently diagnosed NT1 were recruited from three sleep medicine centers in the Netherlands. The control group consisted of 15 healthy children, being frequency matched on age and gender.

Finding Suitable Clinical Endpoints for a Potential Treatment of a Rare Genetic Disease: the Case of ARID1B.

There is a lack of reliable, repeatable, and non-invasive clinical endpoints when investigating treatments for intellectual disability (ID). The aim of this study is to explore a novel approach towards developing new endpoints for neurodevelopmental disorders, in this case for ARID1B-related ID. In this study, twelve subjects with ARID1B-related ID and twelve age-matched controls were included in this observational case-control study.

Raising the Cut-Off Level of Anti-Tissue Transglutaminase Antibodies to Detect Celiac Disease Reduces the Number of Small Bowel Biopsies in Children with Type 1 Diabetes: A Retrospective Study.

Objective: To study the optimal cut-off value for anti-tissue transglutaminase type 2 IgA antibodies (TG2A) in serum to select for diagnostic small bowel biopsies for celiac disease in children with type 1 diabetes mellitus.

Study Design: Children with type 1 diabetes mellitus with elevated TG2A titers and duodenal biopsies performed during the course of their diabetes treatment were included. Anti-endomysial antibodies were recorded if present.

Functional and early weight-bearing protocol for achilles tendon ruptures: a retrospective study.

Purpose: Conservative treatment of achilles tendon rupture (ATR) might be favoured in centres with an early weight-bearing protocol, but no consensus exists on the clear definition of an early weight-bearing protocol. The aim of this study is to evaluate the introduction of an early weight-bearing conservative treatment protocol in patients with ATR compared to patients without this protocol.

Methods: A single-centre retrospective study was performed.

An Activating Deletion Variant in the Submembrane Region of Natriuretic Peptide Receptor-B Causes Tall Stature.

Context: C-type natriuretic peptide (CNP) is critically involved in endochondral bone growth. Variants in the genes encoding CNP or its cyclic guanosine monophosphate (cGMP)-forming receptor (natriuretic peptide receptor-B [NPR-B], gene NPR2) cause monogenic growth disorders. Here we describe a novel gain-of-function variant of NPR-B associated with tall stature and macrodactyly of the great toes (epiphyseal chondrodysplasia, Miura type).

Evaluation of a clinical decision rule to guide antibiotic prescription in children with suspected lower respiratory tract infection in The Netherlands: A stepped-wedge cluster randomised trial.

Background: Optimising the use of antibiotics is a key component of antibiotic stewardship. Respiratory tract infections (RTIs) are the most common reason for antibiotic prescription in children, even though most of these infections in children under 5 years are viral. This study aims to safely reduce antibiotic prescriptions in children under 5 years with suspected lower RTI at the emergency department (ED), by implementing a clinical decision rule.