Since its first identification in Scotland, over 1000 cases of unexplained pediatric hepatitis in children have been reported worldwide, including 278 cases in the UK 1 . Here we report investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator subjects, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in liver, blood, plasma or stool from 27/28 cases. We found low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), in 23/31 and 16/23 respectively of the cases tested. In contrast, AAV2 was infrequently detected at low titre in blood or liver from control children with HAdV, even when profoundly immunosuppressed.AAV2, HAdV and HHV-6 phylogeny excluded emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T-cells and B-lineage cells.Proteomic comparison of liver tissue from cases and healthy controls, identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins.HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and in severe cases HHV-6B, may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.
BackgroundThe benefits of using simulation to improve skills and competence in clinical education is well established. A learning need was identified in managing out-of-hours CAMHS (Children and Adolescent Mental Health Service) emergencies, for junior medical trainees. It was recognised that learning could be augmented by widening participation across disciplines and professions. A pilot simulation delivered six months earlier to junior doctors on psychiatric rotation was well received and showed improved confidence.MethodsThe session, comprised an introductory talk and two simulated scenarios, designed to address issues such as capacity, safeguarding, confidentiality and agitation.The training was delivered by a Consultant Paediatrician, Consultant Psychiatrist, a Fellow in Medical Education, Paediatric Registrar and two external actors. A pre-session focus group with psychiatry and paediatric teams identified concerns with assessing paediatric mental health patients after hours and the logistics of referral pathways and resources. Simulation scenarios were formulated to address these concerns and mapped to the Royal College of Psychiatry and Royal College of Paediatrics and Child Health training curriculum. Pre and post session questionnaires were also completed.ResultsSeven participants attended the first session that was delivered; five psychiatry trainees and two paediatric trainees. 15 participants attended the second session; nine psychiatry trainees, four paediatric nurses, one foundation trainee and one GP trainee. Individuals participated in each section of the two scenarios, increasing candidates’ direct experience of the simulation.100% of participants reported feeling confident in all the outcomes assessed, which was an improvement in all domains. 73% of all participants stated they would recommend the course to a colleague, and that it met their learning needs. Free text qualitative feedback indicated a wider range of paediatric mental health topics to be covered.ConclusionsIn future sessions more equal representation amongst the multidisciplinary and inter-professional teams will be sought. The evidence from these sessions and the previous pilot demonstrates that this is an effective, and stimulating way to improve skills in this area. Participants also benefit from sharing knowledge across disciplines and professions whilst developing collaborative working relationships.
RadPaed cross-specialty integrated training was useful, enjoyable and improved confidence. Trainees would like more integrated training across specialities, although it is difficult to know how generalizable this model will be. The RadPaeds event continues to be delivered to trainees including virtually in response to the COVID-19 pandemic and there are aims to expand this to cover other sub-specialities (for example, Neonates).
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