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.
We conducted a survey of Australian and New Zealand anaesthetists designed to quantify self-reported use of cricoid pressure (CP) in patients presumed to be at risk of gastric regurgitation, and to ascertain the underlying justifications used to support individual practice. We aimed to identify the perceived benefits and harms associated with the use of CP and to explore the potential impact of medicolegal concerns on clinical decision-making. We also sought to ascertain the views of Australian and New Zealand anaesthetists on whether recommendations relating to CP should be included in airway management guidelines. We designed an electronic survey comprised of 15 questions that was emailed to 981 randomly selected Fellows of the Australian and New Zealand College of Anaesthetists (ANZCA) by the ANZCA Clinical Trials Network on behalf of the investigators. We received responses from 348 invitees (response rate 35.5%). Of the 348 respondents, 267 (76.9%) indicated that they would routinely use CP for patients determined to be at increased risk of gastric regurgitation. When asked whether participants believed the use of CP reduces the risk of gastric regurgitation, 39.8% indicated yes, 23.8% believed no and 36.3% were unsure. Of the respondents who indicated that they routinely performed CP, 159/267 (60%) indicated that concerns over the potential medicolegal consequences of omitting CP in a patient who subsequently aspirates was one of the main reasons for using CP. The majority (224/337; 66%) of respondents believed that recommendations about the use of CP in airway management guidelines should include individual practitioner judgement, while only 55/337 (16%) respondents believed that routine CP should be advocated in contemporary emergency airway management guidelines.
In contrast to peer-assisted learning (PAL) in clinical training, there is scant literature on the efficacy of PAL during basic medical sciences teaching for preclinical students. A group of senior medical students aimed to design and deliver clinically oriented small-group tutorials after every module in the preclinical curriculum at a United Kingdom medical school. Twenty tutorials were delivered by senior students throughout the year to first- and second-year students. A baseline questionnaire was delivered to inform the development of the program followed by an end-point questionnaire the next year (n = 122). Quizzes were administered before and after five separate tutorials to assess changes in mean student scores. Additionally, each tutorial was evaluated via a questionnaire for participants (n = 949). All five posttutorial quizzes showed a significant improvement in mean student score (P < 0.05). Questionnaires showed students found the program to be relevant and useful for revision purposes and appreciated how tutorials contextualized basic science to clinical medicine. Students appreciated the interactive nature of the sessions and found receiving personalized feedback about their learning and consolidating information with someone familiar with the material to be useful. With the inclusion of the program, students felt there were now an adequate number of tutorials during the year. In conclusion, this study shows that senior medical students can design and deliver a program that adds value to the mostly lecture-based formal preclinical curriculum. We hope that our study can prompt further work to explore the effect of PAL on the teaching of basic sciences during preclinical studies.
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