Empowering Patients and Health Professionals to Address Sexual Health in the Context of Anorectal Malformations and Hirschsprung's Disease.

The aim of this study is to develop a tool that is aligned with patients' and health professionals' needs to address sexual health in the context of anorectal malformations and Hirschsprung's disease. A multiphased participatory action-research was conducted. First, an inventory of needs was made through interviews (11 patients, 11 professionals), three online focus groups (4 patients, 20 professionals), and a questionnaire (38 patients).

Exploring copy number variants in deceased fetuses and neonates with abnormal vertebral patterns and cervical ribs.

Background: Cervical patterning abnormalities are rare in the general population, but one variant, cervical ribs, is particularly common in deceased fetuses and neonates. The discrepancy between the incidence in the general population and early mortality is likely due to indirect selection against cervical ribs. The cause for the co-occurrence of cervical ribs and adverse outcome remains unidentified.

An international survey on anastomotic stricture management after esophageal atresia repair: considerations and advisory statements.

Background: Endoscopic dilatation is the first-line treatment of stricture formation after esophageal atresia (EA) repair. However, there is no consensus on how to perform these dilatation procedures which may lead to a large variation between centers, countries and doctor's experience. This is the first cross-sectional study to provide an overview on differences in endoscopic dilatation treatment of pediatric anastomotic strictures worldwide.

Early KRAS oncogenic driver mutations in nonmucinous tissue of congenital pulmonary airway malformations as an indicator of potential malignant behavior.

The potential for malignant degeneration is the most common reason for some practitioners to resect asymptomatic congenital pulmonary airway malformations (CPAMs). We aimed to investigate the potential of various immunohistochemical (IHC) and genomic biomarkers to predict the presence of mucinous proliferations (MPs) in CPAM. Archival CPAM tissue samples were re-assessed and underwent IHC analysis using a panel of differentiating markers (TTF1/CDX2/CC10/MUC2/MUC5AC/p16/p53/DICER1).

Cost of health care for paediatric patients with sickle cell disease: An analysis of resource use and costs in a European country.

Background: While multiple studies have examined the cost of health care for one aspect of sickle cell disease care, few have focussed on the overall cost of comprehensive care for sickle cell disease.

Methods: We conducted a retrospective cohort study of children with sickle cell disease treated in a comprehensive care centre from 1 January 2015 to 31 December 2016. Health care utilisation of included patients was based upon data from two main sources.

International prospective observational study investigating the disease course and heterogeneity of paediatric-onset inflammatory bowel disease: the protocol of the PIBD-SETQuality inception cohort study.

Introduction: Patients with paediatric-onset inflammatory bowel disease (PIBD) may develop a complicated disease course, including growth failure, bowel resection at young age and treatment-related adverse events, all of which can have significant and lasting effects on the patient's development and quality of life. Unfortunately, we are still not able to fully explain the heterogeneity between patients and their disease course and predict which patients will respond to certain therapies or are most at risk of developing a more complicated disease course. To investigate this, large prospective studies with long-term follow-up are needed.

Three years of growth hormone treatment in young adults with Prader-Willi Syndrome previously treated with growth hormone in childhood: Effects on glucose homeostasis and metabolic syndrome.

Context: Growth hormone (GH) has been approved for children with Prader-Willi syndrome (PWS) and significantly improves body composition in adults with PWS. Adults with PWS are predisposed to develop impaired glucose tolerance (IGT) and diabetes mellitus type 2 (DMT2). Continuation of GH maintains body composition, but GH is known to induce insulin resistance, which might affect glucose homeostasis.

Three years of growth hormone treatment in young adults with Prader-Willi syndrome: sustained positive effects on body composition.

Background: In children with Prader-Willi syndrome (PWS), the benefits of growth hormone treatment are well established. Several one-year studies have shown that growth hormone is also beneficial for adults with PWS, improving body composition. However, little is known about the longer-term effects.

von Willebrand Factor and Factor VIII Clearance in Perioperative Hemophilia A Patients.

Background:  von Willebrand factor (VWF) is crucial for optimal dosing of factor VIII (FVIII) concentrate in hemophilia A patients as it protects FVIII from premature clearance. To date, it is unknown how VWF behaves and what its impact is on FVIII clearance in the perioperative setting.

Aim:  To investigate VWF kinetics (VWF antigen [VWF:Ag]), VWF glycoprotein Ib binding (VWF:GPIbM), and VWF propeptide (VWFpp) in severe and moderate perioperative hemophilia A patients included in the randomized controlled perioperative OPTI-CLOT trial.

Precision Dosing of Doxapram in Preterm Infants Using Continuous Pharmacodynamic Data and Model-Based Pharmacokinetics: An Illustrative Case Series.

Introduction: Current drug dosing in preterm infants is standardized, mostly based on bodyweight. Still, covariates such as gestational and postnatal age may importantly alter pharmacokinetics and pharmacodynamics. Evaluation of drug therapy in these patients is very difficult because objective pharmacodynamic parameters are generally lacking.

Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Infliximab in Pediatric Inflammatory Bowel Disease: A Systematic Review and Revised Dosing Considerations.

Objectives: Infliximab (IFX), a monoclonal antibody directed against tumor necrosis factor alpha is a potent treatment option for inflammatory bowel disease (IBD). Dosing regimens in children are extrapolated from adult data using a fixed, weight-based dose, which is often not adequate. While clinical trials have focused on safety and efficacy, there is limited data on pharmacokinetic characteristics and immunogenicity of IFX in children.

Exploring the Relationship Between Morphine Concentration and Oversedation in Children After Cardiac Surgery.

Titrating analgesic and sedative drugs in pediatric intensive care remains a challenge for caregivers due to the lack of pharmacodynamic knowledge in this population. The aim of the current study is to explore the concentration-effect relationship for morphine-associated oversedation after cardiac surgery in children aged 3 months to 3 years. Data on morphine dosing, as well as morphine plasma concentrations, were available from a previous study on the pharmacokinetics of morphine after cardiac surgery in children.

Towards integrative neuromonitoring of the surgical newborn: A systematic review.

Background: The altered neurodevelopment of children operated on during the neonatal period might be due to peri-operative changes in the homeostasis of brain perfusion. Monitoring of vital signs is a standard of care, but it does not usually include monitoring of the brain.

Objectives: To evaluate methods of monitoring the brain that might be of value.

A Novel, Enriched Population Pharmacokinetic Model for Recombinant Factor VIII-Fc Fusion Protein Concentrate in Hemophilia A Patients.

Background:  The currently published population pharmacokinetic (PK) models used for PK-guided dosing in hemophilia patients are based on clinical trial data and usually not externally validated in clinical practice. The aim of this study was to validate a published model for recombinant factor VIII-Fc fusion protein (rFVIII-Fc) concentrate and to develop an enriched model using independently collected clinical data if required.

Methods:  Clinical data from hemophilia A patients treated with rFVIII-Fc concentrate (Elocta) participating in the United Kingdom Extended Half-Life Outcomes Registry were collected.

Effect of biologicals and JAK inhibitors during pregnancy on health-related outcomes in children of women with inflammatory bowel disease.

Current guidelines advise to maintain immunomodulators and biologicals in pregnant patients because relapse of inflammatory bowel is associated with unfavourable pregnancy outcome. With the exception of Methotrexate, IBD therapy seems not to be related to an increase of congenital malformations or infections requiring hospitalisation of the babies, although the effect the on the developing immune system of the exposed infants remains unknown. In this review we will focus on the effect of IBD drugs on health-related outcomes in children taking into account possible long-term effects of biologicals and immunomodulators, which are transferred across the placenta.

Evaluation of thromboelastometry, thrombin generation and plasma clot lysis time in patients with bleeding of unknown cause: A prospective cohort study.

Introduction: Diagnostic evaluation of patients with a bleeding tendency remains challenging, as no disorder is identified in approximately 50% of patients. An impaired interplay of several haemostatic factors might explain bleeding phenotype in these patients.

Objective: To investigate whether global haemostasis assays are able to identify haemostatic abnormalities in patients with a bleeding tendency unexplained by current diagnostic laboratory tests.

Infantile hypertrophic pyloric stenosis in patients with esophageal atresia.

Background: Patients born with esophageal atresia (EA) have a higher incidence of infantile hypertrophic pyloric stenosis (IHPS), suggestive of a relationship. A shared etiology makes sense from a developmental perspective as both affected structures are foregut derived. A genetic component has been described for both conditions as single entities and EA and IHPS are variable components in several monogenetic syndromes.

Maternal Prenatal Mood, Pregnancy-Specific Worries, and Early Child Psychopathology: Findings From the DREAM BIG Consortium.

Objective: Few studies have attempted to identify how distinct dimensions of maternal prenatal affective symptoms relate to offspring psychopathology. We defined latent dimensions of women's prenatal affective symptoms and pregnancy-specific worries to examine their association with early offspring psychopathology in three prenatal cohorts.

Method: Data were used from three cohorts of the DREAM-BIG consortium: Avon Longitudinal Study of Parents and Children (ALSPAC [N = 12,515]), Generation R (N = 6,803), and the Canadian prenatal cohort Maternal Adversity, Vulnerability, and Neurodevelopment (MAVAN [N = 578]).

Diurnal rhythmicity in breast-milk glucocorticoids, and infant behavior and sleep at age 3 months.

Purpose: In previous studies, associations between breast-milk cortisol levels obtained on one occasion and infant neurodevelopment were demonstrated. However, more recent evidence indicates that breast-milk cortisol and cortisone concentrations follow the diurnal rhythm of maternal hypothalamus-pituitary-adrenal axis, peaking in the early morning and with a nadir at midnight. We studied associations between breast-milk glucocorticoid (GC) rhythmicity, and infant behavior and sleep.

Longitudinal body composition assessment in healthy term-born infants until 2 years of age using ADP and DXA with vacuum cushion.

Objectives: Accelerated gain in fat mass (FM) in early life increases the risk for adult diseases. Longitudinal data on infant body composition are crucial for clinical and research use, but very difficult to obtain due to limited measurement tools and unsuccessful measurements between age 6-24 months. We compared FM% by dual-energy X-ray absorptiometry (DXA), with cushion to reduce movement artifacts, with FM% by air-displacement plethysmography (ADP) and evaluated the reliability of this cushion during DXA by comparing FM% with and without cushion.

Circulating Antibody-Secreting Cell Response During Mycoplasma pneumoniae Childhood Pneumonia.

Background: We recently demonstrated that the measurement of Mycoplasma pneumoniae (Mp)-specific immunoglobulin (Ig)M antibody-secreting cells (ASCs) improved diagnosis of Mp infection. Here, we aimed to describe Mp ASC kinetics and duration in comparison to conventional measures such as pharyngeal Mp deoxyribonucleic acid (DNA) and serum antibodies.

Methods: This is a prospective longitudinal study of 63 community-acquired pneumonia (CAP) patients and 21 healthy controls (HCs), 3-18 years of age, from 2016 to 2017.

Prenatal and childhood predictors of hair cortisol concentration in mid-childhood and early adolescence.

Background: Hair cortisol concentration (HCC) is an increasingly used measure of systemic cortisol concentration. However, determinants of HCC in children and adolescents are unclear because few prospective studies have been conducted to date.

Study Design: We followed 725 children in Project Viva, a pre-birth cohort study of mothers and children, who provided hair samples at mid-childhood (median age: 7.

Nontraumatic Myelopathy in Malawi: A Prospective Study in an Area with High HIV Prevalence.

Nontraumatic myelopathy causes severe morbidity and is not uncommon in Africa. Clinically, patients often present with paraplegia, and extrinsic cord compression and transverse myelitis are most common causes. Data on exact pathogenesis are scanty because of limitations in diagnostic methods.

von Willebrand factor and factor VIII levels after desmopressin are associated with bleeding phenotype in type 1 VWD.

The bleeding phenotype of patients with type 1 von Willebrand disease (VWD) is very heterogeneous. We hypothesized that this heterogeneity may partly be explained by variability in response of von Willebrand factor (VWF) and factor VIII (FVIII) levels to stress during hemostatic challenges. We therefore investigated whether VWF and FVIII levels after administration of desmopressin, which mimic in vivo hemostatic response during hemostatic challenges, explain the heterogeneity in bleeding phenotype of patients with type 1 VWD.