The Future of Clinical Trial Design: The Transition from Hard Endpoints to Value-Based Endpoints.

Clinical trials have been conducted since 500 BC. Currently, the methodological gold standard is the randomized controlled clinical trial, introduced by Austin Bradford Hill. This standard has produced enormous amounts of high-quality evidence, resulting in evidence-based clinical guidelines for physicians.

IgG Fc glycosylation as an axis of humoral immunity in childhood.

IgG Fc glycans were characterized in 225 healthy children and 40 children with unexplained recurrent respiratory infections, revealing age-dependent variation and suggesting a role for IgG glycosylation in immunocompetence.

Repertoire Sequencing of B Cells Elucidates the Role of UNG and Mismatch Repair Proteins in Somatic Hypermutation in Humans.

The generation of high-affinity antibodies depends on somatic hypermutation (SHM). SHM is initiated by the activation-induced cytidine deaminase (AID), which generates uracil (U) lesions in the B-cell receptor (BCR) encoding genes. Error-prone processing of U lesions creates a typical spectrum of point mutations during SHM.

No radiographic wrist damage after treatment to target in recent-onset juvenile idiopathic arthritis.

Background: To evaluate radiographic progression of patients with new-onset juvenile idiopathic arthritis (JIA) in response to an early, tightly-controlled, treatment-to-target.

Methods: Patients with JIA participating in the BeSt-for-Kids-study, randomized to 3 treatment strategy arms, were eligible if at least 1 conventional wrist-radiograph was available. Bone damage as reflected by carpal length was assessed using the Poznanski-score.

Association of Use of the Neonatal Early-Onset Sepsis Calculator With Reduction in Antibiotic Therapy and Safety: A Systematic Review and Meta-analysis.

Importance: The neonatal early-onset sepsis (EOS) calculator is a clinical risk stratification tool increasingly used to guide the use of empirical antibiotics for newborns. Evidence on the effectiveness and safety of the EOS calculator is essential to inform clinicians considering implementation.

Objective: To assess the association between management of neonatal EOS guided by the neonatal EOS calculator (compared with conventional management strategies) and reduction in antibiotic therapy for newborns.

IL-10 signaling in dendritic cells controls IL-1β-mediated IFNγ secretion by human CD4 T cells: relevance to inflammatory bowel disease.

Uncontrolled interferon γ (IFNγ)-mediated T-cell responses to commensal microbiota are a driver of inflammatory bowel disease (IBD). Interleukin-10 (IL-10) is crucial for controlling these T-cell responses, but the precise mechanism of inhibition remains unclear. A better understanding of how IL-10 exerts its suppressive function may allow identification of individuals with suboptimal IL-10 function among the heterogeneous population of IBD patients.

De novo variants in CNOT3 cause a variable neurodevelopmental disorder.

As a result of exome-based sequencing work performed by the DDD study, de novo variants in CNOT3 have emerged as a newly recognised cause of a developmental disorder. This paper describes molecular and clinical details of 16 probands with developmental disorders and de novo CNOT3 variants. It is the first such description of the developmental phenotype associated with CNOT3 variants.

Pharmacokinetics and safety of tobramycin nebulization with the I-neb and PARI-LC Plus in children with cystic fibrosis: A randomized, crossover study.

Aims: We aimed to compare the pharmacokinetics (PK) and safety profile of tobramycin inhalation solution (TIS) using the I-neb device to the standard PARI-LC Plus nebulizer in children with cystic fibrosis.

Methods: A randomized, open-label, crossover study was performed. In 2 separate study visits, blood samples from 22 children were collected following TIS nebulization with I-neb (75 mg) and PARI-LC Plus (300 mg).

Effect of Cognitive Behavioral Therapy on Clinical Disease Course in Adolescents and Young Adults With Inflammatory Bowel Disease and Subclinical Anxiety and/or Depression: Results of a Randomized Trial.

Background: Anxiety and depressive symptoms are prevalent in patients with inflammatory bowel disease (IBD) and may negatively influence disease course. Disease activity could be affected positively by treatment of psychological symptoms. We investigated the effect of cognitive behavioral therapy (CBT) on clinical disease course in 10-25-year-old IBD patients experiencing subclinical anxiety and/or depression.

Childhood epilepsy with a small number of seizures may be left untreated: an international prospective study.

It is unknown whether treatment with antiepileptic drugs in children with epilepsy with a presumed good prognosis is always necessary. We aimed to study the course of newly diagnosed epilepsy in children with a presumed good prognosis who are managed without AED treatment. A total of 151 children (one month to 12 years of age) with two to five lifetime unprovoked seizures (excluding febrile convulsions), were followed for three years.

Target attainment of cefotaxime in critically ill children with meningococcal septic shock as a model for cefotaxime dosing in severe pediatric sepsis.

Reduced target attainment of β-lactam antibiotics is reported in critically ill patients. However, as target attainment of cefotaxime in severely ill pediatric sepsis patients may differ from adults due to age-related variation in pharmacokinetics, we aimed to assess target attainment of cefotaxime in this pilot study using meningococcal septic shock patients as a model for severe sepsis. Secondary analysis of prospectively collected data from a randomized controlled trial.

Correction to: Imaging of Bronchial Pathology in Antibody Deficiency: Data from the European Chest CT Group.

In the original version of this article unfortunately two authors were missing: Dr. Jürgen Weidemann and Dr. Daniel Berthold.

Effects of immunomodulation in classic infantile Pompe patients with high antibody titers.

Purpose: To evaluate whether immunomodulation can eliminate high sustained antibody levels, and thereby improve clinical outcome in classic infantile Pompe patients receiving enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA).

Methods: Three patients (two cross-reactive immunologic material (CRIM) negative) with high sustained antibodies received a three-week treatment protocol with Rituximab and Bortezomib, followed by daily Rapamycin and monthly IVIG. Patients received 40 mg/kg/week rhGAA.

The Outcome of the Single Step Questionnaire in Pectus Excavatum Patients is Phase Dependent.

Introduction:  Pectus excavatum (PE) is the most common chest wall deformity. Patients with PE may have cosmetic complaints, restricted physical capabilities, or both and may seek surgical correction. One method to assess satisfaction after surgery is the single step questionnaire (SSQ).

A 3-Year-Old Girl With a Mediastinal Mass.

A 3-year-old girl was referred to a pediatric pulmonologist for dyspnea and recurrent upper respiratory tract infections (RTIs). The patient was born full term to unrelated Dutch parents after an uneventful pregnancy and birth. The year before presentation, she had suffered from pneumonia and > 10 upper RTIs.

Sports activity in adolescents in the Netherlands with a pectus excavatum; the impact of surgery.

Purpose: Pectus excavatum (PE) is the most common chest wall deformity in adolescents. The main complaint is cosmetic, but many patients also complain about exertional dyspnea. This may lead to the patient seeking surgery of the thoracic wall deformity (TWD).

Youth With Type 1 Diabetes Taking Responsibility for Self-Management: The Importance of Executive Functioning in Achieving Glycemic Control: Results From the Longitudinal DINO Study.

Objective: Successful self-management of type 1 diabetes requires cognitive skills such as executive functioning (EF). In the transition to adolescence, youth take over responsibility for diabetes management. We set out to test: ) the association between EF and glycemic control over time and ) whether this association was moderated by: ) youth, shared, or parent responsibility for diabetes management and ) youth's age.

Imaging of Bronchial Pathology in Antibody Deficiency: Data from the European Chest CT Group.

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings.

Physical activity after mild traumatic brain injury: What are the relationships with fatigue and sleep quality?

Objectives: To determine self-reported physical activity (PA) levels and relationships with fatigue and sleep quality in adolescents and young adults after mild traumatic brain injury (mTBI).

Setting: Follow-up 6-18 months after visiting the emergency department of one of 2 general hospitals.

Participants: Forty-nine adolescents and young adults aged 12-25 years (mean 18.

Risk of Clinically Relevant Pericardial Effusion After Pediatric Cardiac Surgery.

Pericardial effusion (PE) after pediatric cardiac surgery is common. Because of the lack of a uniform classification of the presence and severity of PE, we evaluated PE altering clinical management: clinically relevant PE. Risk factors for clinically relevant PE were studied.

Impaired social functioning in children with narcolepsy.

Study Objectives: To explore impairments in social functioning in children with narcolepsy compared to healthy children.

Methods: Parents of 53 pediatric patients with narcolepsy type 1 and 64 matched healthy children completed the Social Responsiveness Scale (SRS) and the Child Behavior Checklist 6-18 (CBCL 6-18).

Results: Patients scored significantly higher on the total score of the SRS (median 56, interquartile range [IQR] 23.

Early cost-utility estimation of the surgical correction of pectus excavatum with the Nuss bar.

Objectives: The surgical correction of pectus excavatum (PE) with a Nuss bar provides satisfactory outcomes, but its cost-effectiveness is yet unproven. We prospectively analysed early outcomes and costs for Nuss bar placement.

Methods: Fifty-four patients aged 16 years or older (6 females and 48 males; mean age, 17.

Barriers and Facilitators When Implementing Web-Based Disease Monitoring and Management as a Substitution for Regular Outpatient Care in Pediatric Asthma: Qualitative Survey Study.

Background: Despite their potential benefits, many electronic health (eHealth) innovations evaluated in major studies fail to integrate into organizational routines, and the implementation of these innovations remains problematic.

Objective: The purpose of this study was to describe health care professionals' self-identified perceived barriers and facilitators for the implementation of a Web-based portal to monitor asthmatic children as a substitution for routine outpatient care. Also, we assessed patients' (or their parents) satisfaction with this eHealth innovation.

Translating Sepsis-3 Criteria in Children: Prognostic Accuracy of Age-Adjusted Quick SOFA Score in Children Visiting the Emergency Department With Suspected Bacterial Infection.

Recent attempts to translate Sepsis-3 criteria to children have been restricted to PICU patients and did not target children in emergency departments (ED). We assessed the prognostic accuracy of the age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) and compared the performance to SIRS and the quick Pediatric Logistic Organ Dysfunction-2 score (qPELOD-2). We studied whether the addition of lactate (qSOFA-L) would increase prognostic accuracy.