Exome and genome sequencing in adults with undiagnosed disease: a prospective cohort study.

BACKGROUND: Exome and genome sequencing have been demonstrated to increase diagnostic yield in paediatric populations, improving treatment options and providing risk information for relatives. There are limited studies examining the clinical utility of these tests in adults, who currently have limited access to this technology. METHODS: Patients from adult and cancer genetics clinics across Toronto, Ontario, Canada were recruited into a prospective cohort study evaluating the diagnostic utility of exome and genome sequencing in adults. Eligible patients were ≥18 years of age and suspected of having a hereditary disorder but had received previous uninformative genetic test results. In total, we examined the diagnostic utility of exome and genome sequencing in 47 probands and 34 of their relatives who consented to participate and underwent exome or genome sequencing. RESULTS: Overall, 17% (8/47) of probands had a pathogenic or likely pathogenic variant identified in a gene associated with their primary indication for testing. The diagnostic yield for patients with a cancer history was similar to the yield for patients with a non-cancer history (4/18 (22%) vs 4/29 (14%)). An additional 24 probands (51%) had an inconclusive result. Secondary findings were identified in 10 patients (21%); three had medically actionable results. CONCLUSIONS: This study lends evidence to the diagnostic utility of exome or genome sequencing in an undiagnosed adult population. The significant increase in diagnostic yield warrants the use of this technology. The identification and communication of secondary findings may provide added value when using this testing modality as a first-line test.

Thematic description of factors linked with extended-spectrum beta-lactamase-producing Enterobacteriaceae in humans.

Background: Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are associated with serious antimicrobial-resistant infections in Canadians. Humans are exposed to ESBL-producing Enterobacteriaceae through many interconnected pathways. To better protect Canadians, it is important to generate an understanding of which sources and activities contribute most to ESBL exposure and infection pathways in Canada. Objective: The aims of this scoping review were to thematically describe factors potentially associated with ESBL-producing Enterobacteriaceae colonization, carriage and/or infection in humans from countries with a very high human development index and describe the study characteristics. Methods: Four databases (PubMed, CAB Direct, Web of Science, EBSCOhost) were searched to retrieve potentially relevant studies. Articles were screened for inclusion, and factors were identified, grouped thematically and described. Results: The review identified 381 relevant articles. Factors were grouped into 13 themes: antimicrobial use, animals, comorbidities and symptoms, community, demographics, diet and substance use, health care, household, occupation, prior ESBL colonization/carriage/infection, residential care, travel, and other. The most common themes reported were demographics, health care, antibiotic use and comorbidities and symptoms. Most articles reported factors in hospital settings (86%) and evaluated factors for ESBL-producing Enterobacteriaceae infections (52%). Conclusion: This scoping review provided valuable information about which factor themes have been well described (e.g., health care) and which have been explored less frequently (e.g., diet or animal contact). Themes identified spanned human, animal and environmental contexts and settings, supporting the need for a diversity of perspectives and a multisectoral approach to mitigating exposure to antimicrobial resistance.