www.coronabambini.ch: Development and usage of an online decision support tool for paediatric COVID-19-testing in Switzerland: a cross-sectional analysis.

OBJECTIVES: To describe the development and usage of www.coronabambini.ch as an example of a paediatric electronic public health application and to explore its potential and limitations in providing information on disease epidemiology and public health policy implementation. DESIGN: We developed and maintained a non-commercial online decision support tool, www.coronabambini.ch, to translate the Swiss Federal Office of Public Health (FOPH) paediatric (age 0-18 years) COVID-19 guidelines around testing and school/daycare attendance for caregivers, teachers and healthcare personnel. We analysed the online decision tool as well as a voluntary follow-up survey from October 2020 to September 2021 to explore its potential as a surveillance tool for public health policy and epidemiology. PARTICIPANTS: 68 269 users accessed and 52 726 filled out the complete online decision tool. 3% (1399/52 726) filled out a voluntary follow-up. 92% (18 797/20 330) of users were parents. RESULTS: Certain dynamics of the pandemic and changes in testing strategies were reflected in the data captured by www.coronabambini.ch, for example, in terms of disease epidemiology, gastrointestinal symptoms were reported more frequently in younger age groups (13% (3308/26 180) in children 0-5 years vs 9% (3934/42 089) in children ≥6 years, χ2=184, p≤0.001). As a reflection of public health policy, the proportion of users consulting the tool for a positive contact without symptoms in children 6-12 years increased from 4% (1415/32 215) to 6% (636/9872) after the FOPH loosened testing criteria in this age group, χ2=69, p≤0.001. Adherence to the recommendation was generally high (84% (1131/1352)) but differed by the type of recommendation: 89% (344/385) for 'stay at home and observe', 75% (232/310) for 'school attendance'. CONCLUSIONS: Usage of www.coronabambini.ch was generally high in areas where it was developed and promoted. Certain patterns in epidemiology and adherence to public health policy could be depicted but selection bias was difficult to measure showing the potential and challenges of digital decision support as public health tools.

[Blended Learning With Virtual Pediatric Emergency Patients for Medical Students]. / Blended Learning mit Virtuellen Kindernotfallpatientinnen und -patienten für Studierende.

Blended Learning With Virtual Pediatric Emergency Patients for Medical Students Abstract. Treating critically ill children is a major challenge for learners. Medical Students often feel inadequately prepared for their later role as physicians. This article describes the implementation and evaluation of blended learning using virtual patients (VP) during the student rotation at the pediatric emergency department Inselspital Bern. Students rated the project as highly beneficial and recommended its integration into the entire clinical curriculum.

Innovating Pediatric Emergency Care and Learning Through Interprofessional Briefing and Workplace-Based Assessment: A Qualitative Study.

BACKGROUND: Managing pediatric emergencies can be both clinically and educationally challenging with little existing research on how to improve resident involvement. Moreover, nursing input is frequently ignored. We report here on an innovation using interprofessional briefing (iB) and workplace-based assessment (iWBA) to improve the delivery of care, the involvement of residents, and their assessment. METHODS: Over a period of 3 months, we implement an innovation using iB and iWBA for residents providing emergency pediatric care. A constructivist thematic analysis approach was used to collect and analyze data from 4 focus groups (N = 18) with nurses (4), supervisors (5), and 2 groups of residents (4 + 5). RESULTS: Residents, supervisors, and nurses all felt that iB had positive impacts on learning, teamwork, and patient care. Moreover, when used, iB seemed to play an important role in enhancing the impact of iWBA. Although iB and iWBA seemed to be accepted and participants described important impacts on emergency department culture, conducting of both iB and iWBA could be sometimes challenging as opposed to iB alone mainly because of time constraints. CONCLUSIONS: Interprofessional briefing and iWBA are promising approaches for not only resident involvement and learning during pediatric emergencies but also enhancing team function and patient care. Nursing involvement was pivotal in the success of the innovation enhancing both care and resident learning.

GRIN2B mutations in West syndrome and intellectual disability with focal epilepsy.

OBJECTIVE: To identify novel epilepsy genes using a panel approach and describe the functional consequences of mutations. METHODS: Using a panel approach, we screened 357 patients comprising a vast spectrum of epileptic disorders for defects in genes known to contribute to epilepsy and/or intellectual disability (ID). After detection of mutations in a novel epilepsy gene, we investigated functional effects in Xenopus laevis oocytes and screened a follow-up cohort. RESULTS: We revealed de novo mutations in GRIN2B encoding the NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor in 2 individuals with West syndrome and severe developmental delay as well as 1 individual with ID and focal epilepsy. The patient with ID and focal epilepsy had a missense mutation in the extracellular glutamate-binding domain (p.Arg540His), whereas both West syndrome patients carried missense mutations within the NR2B ion channel-forming re-entrant loop (p.Asn615Ile, p.Val618Gly). Subsequent screening of 47 patients with unexplained infantile spasms did not reveal additional de novo mutations, but detected a carrier of a novel inherited GRIN2B splice site variant in close proximity (c.2011-5_2011-4delTC). Mutations p.Asn615Ile and p.Val618Gly cause a significantly reduced Mg(2+) block and higher Ca(2+) permeability, leading to a dramatically increased Ca(2+) influx, whereas p.Arg540His caused less severe disturbance of channel function, corresponding to the milder patient phenotype. INTERPRETATION: We identified GRIN2B gain-of-function mutations as a cause of West syndrome with severe developmental delay as well as of ID with childhood onset focal epilepsy. Severely disturbed channel function corresponded to severe clinical phenotypes, underlining the important role of facilitated NMDA receptor signaling in epileptogenesis.

Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes.

Idiopathic focal epilepsy (IFE) with rolandic spikes is the most common childhood epilepsy, comprising a phenotypic spectrum from rolandic epilepsy (also benign epilepsy with centrotemporal spikes, BECTS) to atypical benign partial epilepsy (ABPE), Landau-Kleffner syndrome (LKS) and epileptic encephalopathy with continuous spike and waves during slow-wave sleep (CSWS). The genetic basis is largely unknown. We detected new heterozygous mutations in GRIN2A in 27 of 359 affected individuals from 2 independent cohorts with IFE (7.5%; P = 4.83 × 10(-18), Fisher's exact test). Mutations occurred significantly more frequently in the more severe phenotypes, with mutation detection rates ranging from 12/245 (4.9%) in individuals with BECTS to 9/51 (17.6%) in individuals with CSWS (P = 0.009, Cochran-Armitage test for trend). In addition, exon-disrupting microdeletions were found in 3 of 286 individuals (1.0%; P = 0.004, Fisher's exact test). These results establish alterations of the gene encoding the NMDA receptor NR2A subunit as a major genetic risk factor for IFE.

Targeted next generation sequencing as a diagnostic tool in epileptic disorders.

PURPOSE: Epilepsies have a highly heterogeneous background with a strong genetic contribution. The variety of unspecific and overlapping syndromic and nonsyndromic phenotypes often hampers a clear clinical diagnosis and prevents straightforward genetic testing. Knowing the genetic basis of a patient's epilepsy can be valuable not only for diagnosis but also for guiding treatment and estimating recurrence risks. METHODS: To overcome these diagnostic restrictions, we composed a panel of genes for Next Generation Sequencing containing the most relevant epilepsy genes and covering the most relevant epilepsy phenotypes known so far. With this method, 265 genes were analyzed per patient in a single step. We evaluated this panel on a pilot cohort of 33 index patients with concise epilepsy phenotypes or with a severe but unspecific seizure disorder covering both sporadic and familial cases. KEY FINDINGS: We identified presumed disease-causing mutations in 16 of 33 patients comprising sequence alterations in frequently as well as in less commonly affected genes. The detected aberrations encompassed known and unknown point mutations (SCN1A p.R222X, p. E289V, p.379R, p.R393H; SCN2A p.V208E; STXBP1 p.R122X; KCNJ10 p.L68P, p.I129V; KCTD7 p.L108M; KCNQ3 p.P574S; ARHGEF9 p.R290H; SMS p.F58L; TPP1 p.Q278R, p.Q422H; MFSD8 p.T294K), a putative splice site mutation (SCN1A c.693A> p.T/P231P) and small deletions (SCN1A p.F1330Lfs3X [1 bp]; MFSD8 p.A138Dfs10X [7 bp]). All mutations have been confirmed by conventional Sanger sequencing and, where possible, validated by parental testing and segregation analysis. In three patients with either Dravet syndrome or myoclonic epilepsy, we detected SCN1A mutations (p.R222X, p.P231P, p.R393H), even though other laboratories had previously excluded aberrations of this gene by Sanger sequencing or high-resolution melting analysis. SIGNIFICANCE: We have developed a fast and cost-efficient diagnostic screening method to analyze the genetic basis of epilepsies. We were able to detect mutations in patients with clear and with unspecific epilepsy phenotypes, to uncover the genetic basis of many so far unresolved cases with epilepsy including mutation detection in cases in which previous conventional methods yielded falsely negative results. Our approach thus proved to be a powerful diagnostic tool that may contribute to collecting information on both common and unknown epileptic disorders and in delineating associated phenotypes of less frequently mutated genes.

Fatal adenovirus hepatitis during maintenance therapy for childhood acute lymphoblastic leukemia.

Disseminated adenoviral infection with hepatitis is rare in children undergoing standard chemotherapy. We report on a 3(1/2)-year-old male with fatal adenovirus hepatitis receiving maintenance chemotherapy for acute lymphoblastic leukemia (ALL). Adenoviral hepatitis was proven by histology, viral culture, and PCR in a liver biopsy. Quantitative real-time PCR in the peripheral blood showed adenoviral DNA copy number >10(9)/ml. Despite aggressive supportive care and antiviral treatment with cidofovir, the patient died rapidly due to fulminant liver failure. Diagnostic and treatment options for adenovirus infection remain unsatisfactory for these patients. We propose suggestions for diagnosis and therapy.