Background Ataxia-telangiectasia is an autosomal recessive, multi-system, and life-shortening disease caused by mutations in the ataxia-telangiectasia mutated gene. Although widely reported, there are no studies that give a comprehensive picture of this intriguing condition. Objectives Understand the natural history of ataxia-telangiectasia (A-T), as reported in scientific literature. Search methods 107 search terms were identified and divided into 17 searches. Each search was performed in PubMed, Ovid SP (MEDLINE) 1946-present, OVID EMBASE 1980 –present, Web of Science core collection, Elsevier Scopus, and Cochrane Library. Selection criteria All human studies that report any aspect of A-T. Data collection and analysis Search results were de-duplicated, data extracted (including author, publication year, country of origin, study design, population, participant characteristics, and clinical features). Quality of case-control and cohort studies was assessed by the Newcastle-Ottawa tool. Findings are reported descriptively and where possible data collated to report median (interquartile range, range) of outcomes of interest. Main results 1314 cases reported 2134 presenting symptoms. The most common presenting symptom was abnormal gait (1160 cases; 188 studies) followed by recurrent infections in classical ataxia-telangiectasia and movement disorders in variant ataxia-telangiectasia. 687 cases reported 752 causes of death among which malignancy was the most frequently reported cause. Median (IQR, range) age of death (n = 294) was 14 years 0 months (10 years 0 months to 23 years 3 months, 1 year 3 months to 76 years 0 months). Conclusions This review demonstrates the multi-system involvement in A-T, confirms that neurological symptoms are the most frequent presenting features in classical A-T but variants have diverse manifestations. We found that most individuals with A-T have life limited to teenage or early adulthood. Predominance of case reports, and case series demonstrate the lack of robust evidence to determine the natural history of A-T. We recommend population-based studies to fill this evidence gap.

Ataxia is a common presentation to an acute paediatric unit and it can often be difficult to determine the cause. It is important to distinguish between serious causes, for example, brain tumours and encephalitis, and more benign causes in order to guide investigations and treatment. In this review, we describe the different types of ataxia, the causes associated with them, the examination findings and what investigations to perform in order to make a diagnosis.

Background Many factors have been related to the development of childhood asthma but there is inconsistency between studies. Objective To understand how early life factors are linked to the development of the various asthma phenotypes at age 6 years in the Southampton Women's Survey (SWS) children's cohort. Methods Data was collected from 940 children and their parents, primarily through questionnaires during pregnancy and at 6m, 1, 3 and 6 years. Prevalent asthma was defined by a doctor's diagnosis and a wheezing episode in the last year. Data was analysed using STATA v9. A relative risk analysis using a univariate approach was undertaken, followed by a multivariate analysis. Results Both maternal (RR=1.61, p=0.041) and paternal (RR=2.05, p=0.002) atopic disease increased the risk of asthma at age 6 years. The risk increased with atopy, defined as a positive skin prick test, at 3 years (RR=3.05, p<0.001) and with wheeze in the first 3 years (RR=8.79, p<0.001). Episodes of bronchiolitis and chest infections were associated, in a dose-dependent manner, with the risk of asthma (RR=1.50, p=0.022). Predictors in the multivariate model were wheeze in the first 3 years (RR=10.74, p<0.001), atopy (RR=2.87, p<0.001) and maternal atopy (RR=2.22, p=0.011).When asthma at age 6 years was split into atopic and non-atopic asthma, the predictors were very different. Atopic asthma was associated with paternal atopy (RR=4.13, p=0.002), male sex (RR=2.56, p=0.030), atopy at 3 years (RR=10.31, p<0.001) and wheeze in the first 3 years (RR=5.91, p=0.004). In the multivariate analysis, the following were predictive: wheeze in the first 3 years (RR=13.55, p=0.012), atopy at 3 years (RR=10.13,<0.001), paternal atopy (RR=2.97, p=0.017) and a 12 month infant dietary pattern that follows current guidelines (RR=1.79, p=0.016). For non-atopic asthma, bronchiolitis or chest infections (RR=1.76, p=0.047), wheeze in the first 3 years (RR=20.69, p=0.003) and tobacco smoke exposure at 6 years (RR=2.16, p=0.035) increased the risk. Only wheeze in the first 3 years remained in the multivariate model. Conclusions Different hereditary and early life factors modify the risk of atopic and non-atopic asthma at 6 years of age. This suggests that these two asthma phenotypes have different pathophysiologies. The p38 MAPK pathway is increasingly recognised as important in inflammation leading to systemic vascular disease but its role in pulmonary vascular disease is unclear. Our group has previously identified the p38MAPKα isoform to be critical in hypoxic-induced proliferation of pulmonary artery fibroblasts, a key step in the pathogenesis of pulmonary vascular remodelling. This study sought to investigate the role of p38MAPK in animal models of pulmonary hypertension and in human disease. Methods Sprague Dawley rats were exposed to chronic hypoxia for 14 days and received a selective p38 MAPKα inhibitor from day 1 Pathophysiology of pulmonary vascular remodelling S36Abstract S34 Table 1 DIFFERENT EARLY LIFE FACTORS ARE IMPORTANT IN THE DEVELOPMENT OF AT...

The highest incidence of burns during the summer of 2020 was in the 6-11 years olds which may reflect increased BBQ usage in the summer weather and potentially reduced supervision. Conclusions Gloucestershire ED and PAU has seen upwards trends in burns and dog bites during the pandemic indicative of the burden and stressors placed on households. However, these injuries suggest a lack of supervision and safety in the home and are a safe-guarding concern. Injuries are a preventable cause of morbidity in the paediatric population.This data collection highlights the needs not only in strengthening our public health measures but also in strengthening the services responsible for investigating judiciously safeguarding concerns, detecting vulnerable families, protect children from maltreatment and promoting their overall welfare.

Although there were no significant differences in mortality between OP and controls, OP mortality was high at 25.0% compared to 8.3%. However, the deaths among the OP cohort were not directly related to OP itself. Patients with OP had higher risk of having moderate to severe intraventricular haemorrhage (IVH grades 2-3 by Volpe classification) OR 5.00 (p<0.05) and combined moderate-severe IVH with mortality, OR 5.86, p<0.01. Conclusions OP is a rare complication among smaller VLBW infants. There was a high incidence of mortality of 25.0%, air leak syndrome and moderate to severe IVH.

highlighting the pandemic's disruption to the care of patients with long-term conditions. Contrary to guidance, 14.73% of patients were not tested in the nine months post-lockdown, potentially reflecting reluctance to attend hospital during the pandemic. Nevertheless, where results were available, lockdown seemed to have a positive impact on HbA1c despite the enforced use of telemedicine, unless the patient was already close to target. It is possible that lockdown provided more routine and parental supervision for those with initially high HbA1c but disrupted the successful routine and sporting activities of those initially closer to target.

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