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IMPORTANCE: Widespread adoption of rapid genomic testing in pediatric critical care requires robust clinical and laboratory pathways that provide equitable and consistent service across health care systems.OBJECTIVE: To prospectively evaluate the performance of a multicenter network for ultra-rapid genomic diagnosis in a public health care system.DESIGN, SETTING, AND PARTICIPANTS: Descriptive feasibility study of critically ill pediatric patients with suspected monogenic conditions treated at 12 Australian hospitals between March 2018 and February 2019, with data collected to May 2019. A formal implementation strategy emphasizing communication and feedback, standardized processes, coordination,distributed leadership, and collective learning was used to facilitate adoption.EXPOSURES Ultra-rapid exome sequencing.MAIN OUTCOMES AND MEASURES: The primary outcome was time from sample receipt to ultra-rapid exome sequencing report. The secondary outcomes were the molecular diagnostic yield, the change in clinical management after the ultra-rapid exome sequencing report, the time from hospital admission to the laboratory report, and the proportion of laboratory reports returned prior to death or hospital discharge RESULTS: The study population included 108 patients with a median age of 28 days (range, 0 days to 17 years); 34% were female; and 57% were from neonatal intensive care units, 33% were from pediatric intensive care units, and 9% were from other hospital wards. The meantime from sample receipt to ultra-rapid exome sequencing report was 3.3 days (95% CI,3.2-3.5 days) and the median time was 3 days (range, 2-7 days). The mean time from hospital admission to ultra-rapid exome sequencing report was 17.5 days (95% CI, 14.6-21.1 days) and 93 reports (86%) were issued prior to death or hospital discharge. A molecular diagnosis was established in 55 patients (51%). Eleven diagnoses (20%) resulted from using the following approaches to augment standard exome sequencing analysis: mitochondrial genome sequencing analysis, exome sequencing–based copy number analysis, use of international databases to identify novel gene–disease associations, and additional phenotyping and RNA analysis. In 42 of 55 patients (76%) with a molecular diagnosis and 6 of 53 patients (11%)without a molecular diagnosis, the ultra-rapid exome sequencing result was considered as having influenced clinical management. Targeted treatments were initiated in 12 patients(11%), treatment was redirected toward palliative care in 14 patients (13%), and surveillance for specific complications was initiated in 19 patients (18%).CONCLUSIONS AND RELEVANCE: This study suggests feasibility of ultra-rapid genomic testing in critically ill pediatric patients with suspected monogenic conditions in the Australian public health care system. However, further research is needed to understand the clinical value of such testing, and the generalizability of the findings to other health care settings. Refereed/Peer-reviewed

Objective: Anecdotally, lower leg skin changes in morbidly obese people appear much improved with weight loss following bariatric surgery. The objective of this study was to compare prevalence of lower leg symptoms in obese patients awaiting, and those who have had, bariatric surgery. Methods: An audit was undertaken, utilising questionnaires, to identify obesity-associated lower leg symptoms: swelling, itchiness, colour changes, hot/burning feeling, eczema and ulcers. There were three groups: those awaiting surgery (‘Obesity Clinic’), those who had surgery (‘Post-Surgery’), and those in ‘Post-Surgery’ recalling pre-operative symptoms (‘Pre-Surgery Recall’). Results: Participants totalled 117; 62 in ‘Obesity Clinic’ and 55 in ‘Post-Surgery’ (81.8% response rate). Overall prevalence of symptoms was significantly lower in ‘Post-Surgery’ (36.4%) compared to ‘Obesity Clinic’ (80.6%) and ‘Pre-Surgery Recall’ (74.5%) (p

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition that forms part of the spectrum of motor neurone disease, which results in progressive weakness and has a poor prognosis. Over the last twenty years, mutations in the SOD1 gene were thought to be the most common cause of the familial form of ALS, accounting for 20% of cases. However, in the last couple of years, hexanucleotide repeat expansions within the C9orf72 gene have been discovered to account for up to 40% of familial ALS, and are now recognised to be the most common known cause. We have recently developed a new assay to analyse C9orf72 expansions, and sought to investigate this in samples that had previously been investigated for SOD1 mutations and found to be negative, over the period of 2003 to 2014. A total of 32.9% (23/70) samples were found to carry pathogenic C9orf72 expansions (>30 repeats), while 2.9% (2/70) were borderline (20–30 repeats) and 50.0% (35/70) were normal (