Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype

Purpose: Wolfram syndrome is a degenerative, recessive rare disease with an onset in childhood. It is caused by mutations in WFS1 or CISD2 genes. More than 200 different variations in WFS1 have been described in patients with Wolfram syndrome, which complicates the establishment of clear genotype-phenotype correlation. The purpose of this study was to elucidate the role of WFS1 mutations and update the natural history of the disease. Methods: This study analyzed clinical and genetic data of 412 patients with Wolfram syndrome published in the last 15 years. Results: (i) 15% of published patients do not fulfill the current ­inclusion criterion; (ii) genotypic prevalence differences may exist among countries; (iii) diabetes mellitus and optic atrophy might not be the first two clinical features in some patients; (iv) mutations are nonuniformly distributed in WFS1; (v) age at onset of diabetes mellitus, hearing defects, and diabetes insipidus may depend on the patient"s genotypic class; and (vi) disease progression rate might depend on genotypic class. Conclusion: New genotype-phenotype correlations were established, disease progression rate for the general population and for the genotypic classes has been calculated, and new diagnostic criteria have been proposed. The conclusions raised could be important for patient management and counseling as well as for the development of treatments for Wolfram syndrome

Availability and use of rapid diagnostic tests for the management of acute childhood infections in Europe : A cross-sectional survey of paediatricians

Background Point-of-care-tests (POCTs) have been advocated to optimise care in patients with infections but their actual use varies. This study aimed to estimate the variability in the adoption of current POCTs by paediatricians across Europe, and to explore the determinants of variability.Methods and findings A cross-sectional survey was conducted of hospital and primary care paediatricians, recruited through professional networks. Questions focused on the availability and use of currently available POCTs. Data were analysed descriptively and using Median Odds Ratio (MOR) to measure variation between countries. Multilevel regression modelling using changes in the area under the receiver operating characteristic curve of models were used to assess the contribution of individual or workplace versus country level factors, to the observed variation. The commonest POCT was urine dipsticks (UD) which were available to >80% of primary care and hospital paediatricians in 68% (13/19) and 79% (23/29) countries, respectively. Availability of all POCTs varied between countries. In primary care, the country (MOR) varied from 1.61 (95%CI: 1.04-2.58) for lactate to 7.28 (95%CI: 3.04-24.35) for UD. In hospitals, the country MOR varied from 1.37 (95%CI:1.04-1.80) for lactate to 11.93 (95%CI:3.35-72.23) for UD. Most paediatricians in primary care (69%, 795/1154) and hospital (81%, 962/1188) would use a diagnostic test in the case scenario of an infant with undifferentiated fever. Multilevel regression modelling showed that the country of work was more important in predicting both the availability and use of POCTs than individual or workplace characteristics.Conclusion There is substantial variability in the adoption of POCTs for the management of acute infections in children across Europe. To inform future implementation of both existing and innovative tests, further research is needed to understand what drives the variation between countries, the needs of frontline clinicians, and the role of diagnostic tests in the management of acute childhood infections.Peer reviewe

Rapid Influenza Testing in Infants and Children Younger than 6 Years in Primary Care : Impact on Antibiotic Treatment and Use of Health Services

This study was partially financed by an unrestricted grant from AstraZeneca Pharmaceutical Spain. The funders had no role in the study design, data col-lection and analysis, decision to publish or preparation of the manuscript.Influenza is often misdiagnosed in children because of the low sensitivity of clinical diagnosis because of nonspecific signs and symptoms. This can be overcome by using digital immunoassays or rapid molecular diagnostic tests with adequate sensitivity and specificity. When using these tests at the patient care site, antibiotic consumption and number of healthcare consultations were reduced

Current primary care management of children aged 1-36 months with urinary tract infections in Europe : large scale survey of paediatric practice

OBJECTIVE: To describe current practice among European paediatricians regarding diagnosis and management of urinary tract infections in children aged 1-36\u2005months and to compare these practices with recently published guidelines. DESIGN: Web-based large scale survey evaluating knowledge of, attitudes towards and the methods for diagnosing, treating and managing urinary tract infections in children. SETTING: Primary and secondary care practices in Europe. SAMPLE: 1129 paediatricians. RESULTS: A diagnosis of urinary tract infection is considered by 62% of the respondents in children aged 1-36\u2005months with unexplained fever. The preferred method of urine collection is use of a bag (53% for infants <3\u2005months and 59% for children 4-36\u2005months of age). 60% of paediatricians agree that oral and parenteral antibiotics have equal efficacy. Co-amoxiclav is the antibiotic of choice for 41% of participants, while 9% prescribe amoxicillin. 80% of respondents prescribe ultrasound in all children with a confirmed urinary tract infection. 63% of respondents prescribe a cystography when abnormalities are revealed during ultrasound evaluation. A quarter of respondents recommend antibiotic prophylaxis for all children with any vesicoureteral reflux. The data among European countries are very heterogeneous. The three most recent urinary tract infection guidelines (the National Institute for Health and Care Excellence (NICE), the American Academy of Paediatrics and the Italian Society of Paediatric Nephrology) are not followed properly. CONCLUSIONS: Management of febrile urinary tract infections remains controversial and heterogeneous in Europe. Simple, short, practical and easy-to-remember guidelines and educational strategies to ensure their implementation should be developed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions