Safe, effective and cost-effective oxygen saturation targets for children and adolescents with respiratory distress: protocol for a randomised controlled trial (OxyKids study).

Introduction: Little is known about the effectiveness and safety of oxygen saturation (SpO2) thresholds in children admitted with respiratory distress. The current 90%-94% threshold could lead to prolonged administration of supplemental oxygen, increased duration of hospital admissions, distress for children and families, and healthcare costs. To balance reducing unnecessary oxygen administration and preventing hypoxia, a lower SpO2 threshold of 88% for oxygen supplementation in children has been suggested.

Conservative Pulmonary Arteriovenous Malformation Screening in Children: Re-Evaluation of Safety.

Introduction: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disease and screening to detect pulmonary arteriovenous malformations (PAVMs) is important to prevent complications. In adults, transthoracic contrast echocardiogram (TTCE) is used to screen PAVMs. In children, a conservative screening method seems to be sufficient to rule out major PAVMs and prevent them from PAVM-related complications.

A novel method to standardise serum IgA measurements shows an increased prevalence of IgA deficiency in young children with recurrent respiratory tract infections.

Objectives: While physicians are often confronted with immunoglobulin A (IgA) deficiency in children with recurrent infections, the clinical relevance of this finding is unclear. Large-scale studies examining the significance of IgA deficiency in children are hampered by differences in techniques for measuring IgA and the physiological increase of IgA with age. Both result in a variety of reference values used for diagnosing IgA deficiency.

Prevalence and Predictors of Uncontrolled Asthma in Children Referred for Asthma and Other Atopic Diseases.

Background: Uncontrolled asthma in children is still highly prevalent despite the availability of effective asthma treatment. We investigated 1) the prevalence of uncontrolled asthma among children referred for asthma and referred for atopic diseases other than asthma (ie food allergy, allergic rhinitis or atopic dermatitis) to secondary care; and 2) the predictors associated with uncontrolled asthma.

Methods: All children (4 to 18 years) referred for asthma or atopic diseases other than asthma to 8 secondary care centers in The Netherlands were invited to an electronic portal (EP).

Design, Synthesis, and Biological Evaluation of Novel Indoles Targeting the Influenza PB2 Cap Binding Region.

In the search for novel influenza inhibitors we evaluated 7-fluoro-substituted indoles as bioisosteric replacements for the 7-azaindole scaffold of Pimodivir, a PB2 (polymerase basic protein 2) inhibitor currently in clinical development. Specifically, a 5,7-difluoroindole derivative was identified as a potent and metabolically stable influenza inhibitor. demonstrated a favorable oral pharmacokinetic profile and in vivo efficacy in mice.

Episodic viral wheeze and multiple-trigger wheeze in preschool children are neither distinct nor constant patterns. A prospective multicenter cohort study in secondary care.

Objectives: To evaluate whether episodic viral wheeze (EVW) and multiple-trigger wheeze (MTW) are clinically distinguishable and stable preschool wheezing phenotypes.

Methods: Children of age 1 to 4 year with recurrent, pediatrician-confirmed wheeze were recruited from secondary care; 189 were included. Respiratory and viral upper respiratory tract infection (URTI) symptoms were recorded weekly by parents in an electronic diary during 12 months.

Asthma medication in children who are overweight/obese: justified treatment?

Background: The prevalence of asthma and obesity have increased over the last decades. A possible association between these two chronic illnesses has been suggested, since the prevalence of asthmatic symptoms rises with increasing Body Mass Index (BMI). However, asthma is only one of several possible causes of shortness of breath in obese children.

Point-of-care C-reactive protein to assist in primary care management of children with suspected non-serious lower respiratory tract infection: a randomised controlled trial.

Background: Overprescription of antibiotics for lower respiratory tract infections (LRTIs) in children is common, partly due to diagnostic uncertainty, in which case the addition of point-of-care (POC) C-reactive protein (CRP) testing can be of aid.

Aim: To assess whether use of POC CRP by the GP reduces antibiotic prescriptions in children with suspected non-serious LRTI.

Design & Setting: An open, pragmatic, randomised controlled trial in daytime general practice and out-of-hours services.

Screening children for pulmonary arteriovenous malformations: Evaluation of 18 years of experience.

Background: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disease with multi-systemic vascular dysplasia. Early diagnosis through screening is important to prevent serious complications. How best to screen children of affected parents for pulmonary arteriovenous malformations (PAVMs) is often subject to debate.

Sensitization predicts asthma development among wheezing toddlers in secondary healthcare.

Introduction: Some wheezing toddlers develop asthma later in childhood. Sensitization is known to predict asthma in birth cohorts. However, its predictive value in secondary healthcare is uncertain.

Clinical relevance and cost-effectiveness of HLA genotyping in children with Type 1 diabetes mellitus in screening for coeliac disease in the Netherlands.

Aims: To investigate the clinical relevance and cost-effectiveness of human leukocyte antigen (HLA)-genotyping in the Netherlands as a screening tool for the development of coeliac disease in children with Type 1 diabetes mellitus.

Methods: A retrospective analysis was performed in 110 children with Type 1 diabetes mellitus diagnosed between January 1996 and January 2013. All children were screened for coeliac disease using coeliac disease-specific antibodies and HLA genotyping was performed in all children.

Respiratory tract infections and asthma control in children.

Introduction: Asthma control is considered the major goal of asthma management, while many determinants of control are difficult to modify. We studied the association between respiratory infection episodes (RTIs) of various types and asthma control.

Methods: Cross-sectional data were used from children aged 4-18 years with physician-diagnosed asthma who participated in a web-based electronic portal for children with asthma, allergies or infections.

Diagnostic properties of C-reactive protein for detecting pneumonia in children.

Background: The diagnostic value of C-reactive protein (CRP) level for pneumonia in children is unknown. As a first step in the assessment of the value of CRP, a diagnostic study was performed in children at an emergency department (ED).

Methods: In this cross-sectional study, data were retrospectively collected from children presenting with suspected pneumonia at the ED of Antonius Hospital Nieuwegein in The Netherlands between January 2007 and January 2012.

The expert network and electronic portal for children with respiratory and allergic symptoms: rationale and design.

Data on baseline characteristics of children with asthma to predict individual treatment responses are lacking. We aimed to set up a data-collection system which can easily fill this gap in clinical practice.A web-based application was developed, named 'Portal for children with respiratory and allergic symptoms', hereafter called Electronic Portal (EP).

Novel antibiotics targeting respiratory ATP synthesis in Gram-positive pathogenic bacteria.

Emergence of drug-resistant bacteria represents a high, unmet medical need, and discovery of new antibacterials acting on new bacterial targets is strongly needed. ATP synthase has been validated as an antibacterial target in Mycobacterium tuberculosis, where its activity can be specifically blocked by the diarylquinoline TMC207. However, potency of TMC207 is restricted to mycobacteria with little or no effect on the growth of other Gram-positive or Gram-negative bacteria.

[Diagnosis of fetal alcohol spectrum disorders].

Prenatal alcohol exposure may cause decreased growth of the child, congenital abnormalities, specific facial characteristics, and, most importantly, mental retardation and behavioural disorders, all known as fetal alcohol spectrum disorders (FASD). A significant number of pregnant women in the Netherlands drink alcohol, but the prevalence of FASD in our country is unknown. Repeated and high peak blood alcohol concentrations, for example in the case of binge drinking by the mother, result in more severe abnormalities; a safe limit for alcohol consumption in pregnancy cannot be defined.

Common genetic variation in the DKK1 gene is associated with hip axis length but not with bone mineral density and bone turnover markers in young adult men: results from the Odense Androgen Study.

LRP5 was recently confirmed as an important susceptibility gene for osteoporosis. Our objective was to evaluate the effect of DKK1 polymorphisms on bone mineral density (BMD), hip geometry, and bone turnover. DKK1 is a secreted protein that binds to LRP5/6 receptors and inhibits canonical Wnt signaling.

Essentiality of FASII pathway for Staphylococcus aureus.

Recently, Brinster et al. suggested that type II fatty-acid biosynthesis (FASII) is not a suitable antibacterial target for Gram-positive pathogens because they use fatty acids directly from host serum rather than de novo synthesis. Their findings, if confirmed, are relevant for further scientific and financial investments in the development of new drugs targeting FASII.

Sclerostin in mineralized matrices and van Buchem disease.

Sclerostin is an inhibitor of bone formation expressed by osteocytes. We hypothesized that sclerostin is expressed by cells of the same origin and also embedded within mineralized matrices. In this study, we analyzed (a) sclerostin expression using immunohistochemistry, (b) whether the genomic defect in individuals with van Buchem disease (VBD) was associated with the absence of sclerostin expression, and (c) whether this was associated with hypercementosis.

A known SOST gene mutation causes sclerosteosis in a familial and an isolated case from Brazilian origin.

Sclerosteosis is a severe, rare, autosomal recessive bone condition that is characterized by a progressive craniotubular hyperostosis. The main features are a significant sclerosis of the long bones, ribs, pelvis, and skull, leading to facial distortion and entrapment of cranial nerves. Clinical features include a tall stature, nail dysplasia, cutaneous syndactyly of some fingers, and raised intracranial pressure.

Diarylquinolines are bactericidal for dormant mycobacteria as a result of disturbed ATP homeostasis.

An estimated one-third of the world population is latently infected with Mycobacterium tuberculosis. These nonreplicating, dormant bacilli are tolerant to conventional anti-tuberculosis drugs, such as isoniazid. We recently identified diarylquinoline R207910 (also called TMC207) as an inhibitor of ATP synthase with a remarkable activity against replicating mycobacteria.

Genetic analysis and effect of triiodothyronine and prednisone trial on bone turnover in a patient with craniotubular hyperostosis.

Craniotubular hyperostosis are a group of high bone mass disorders related to mutations in the LRP5 and SOST genes, although other causative genes remain to be identified. Little is known about the bone turnover and the response to T3 or glucocorticoids in these patients. We describe a patient with craniotubular hyperostosis, including mutation analyses of the LRP5, SOST, DKK1 and KRM1 genes.

The binding between sclerostin and LRP5 is altered by DKK1 and by high-bone mass LRP5 mutations.

Low-density lipoprotein receptor-related protein 5 (LRP5), a Wnt coreceptor, plays an important role in bone metabolism as loss-of-function and gain-of-function mutations in LRP5 result in the autosomal recessive osteoporosis-pseudoglioma syndrome and autosomal dominant high-bone mass (HBM) phenotypes, respectively. Prior studies suggested that the presence of HBM-associated LRP5 mutations results in decreased antagonism of LRP5-mediated Wnt signaling. In the present study, we investigated six different HBM-LRP5 mutations and confirm that neither Dickkopf1 (DKK1) nor sclerostin efficiently inhibits HBM-LRP5 signaling.

Atopic disease and exhaled nitric oxide in an unselected population of young adults.

Background: Several studies have reported elevated levels of fractional exhaled nitric oxide (FeNO) in atopic patients, particularly in asthmatic patients, suggesting that FeNO is a marker of bronchial inflammation. However, the independent influence of different atopic entities (eczema, allergic rhinitis, and asthma) on FeNO has never been studied in the general population.

Objective: To study the influence of a questionnaire-based diagnosis of atopic diseases and IgE and lung function measurements on FeNO levels.