Children affected by genetic conditions often have multisystem disease, experience substantial morbidity and mortality, and have higher hospitalization rates with longer admissions compared with the general pediatric population.^1-3 The evaluation for a genetic condition in a child, the so-called diagnostic odyssey, typically involves clinical assessment and multiple investigations, many of which are invasive and costly. The diagnostic trajectory can be prolonged, and many children continue to have undiagnosed conditions. Each technological advance in genetic analysis offers an opportunity to improve diagnostic yield, as exemplified by chromosomal microarray over conventional karyotyping,⁴ but none has the diagnostic power of genomic sequencing. Whole-exome sequencing (WES), the analysis of the protein-coding exons of genes, has the potential to revolutionize the diagnosis in children suspected of having monogenic disorders.^5,6 Quiz Ref ID Large-scale studies^7-13 of WES in children with broad clinical presentations report diagnostic rates of 25% to 30%, applying WES after multiple genetic investigations, including single-gene or panel testing. Studies using WES as a last resort result in ascertainment bias toward diagnostically difficult cases because children with conditions diagnosed with an earlier gene test would be excluded. The application of WES to a clinically ascertained, sequencing-naive cohort is needed to understand the full impact of WES in the pediatric clinic and to assist clinicians in knowing when and for whom to consider singleton WES.

To systematically investigate the longer-term clinical and health economic impacts of genomic sequencing for rare-disease diagnoses. We collected information on continuing diagnostic investigation, changes in management, cascade testing, and parental reproductive outcomes in 80 infants who underwent singleton whole-exome sequencing (WES). The median duration of follow-up following result disclosure was 473 days. Changes in clinical management due to diagnostic WES results led to a cost saving of AU$1,578 per quality-adjusted life year gained, without increased hospital service use. Uninformative WES results contributed to the diagnosis of non-Mendelian conditions in seven infants. Further usual diagnostic investigations in those with ongoing suspicion of a genetic condition yielded no new diagnoses, while WES data reanalysis yielded four. Reanalysis at 18 months was more cost-effective than every 6 months. The parents of diagnosed children had eight more ongoing pregnancies than those without a diagnosis. Taking the costs and benefits of cascade testing and reproductive service use into account, there was an additional cost of AU$8,118 per quality-adjusted life year gained due to genomic sequencing. These data strengthen the case for the early use of genomic testing in the diagnostic trajectory, and can guide laboratory policy on periodic WES data reanalysis.

Objective: To examine the association between long‐term health conditions and being out of the labour force among older Australians. Design, setting and participants: Retrospective analysis of cross‐...

One group often identified as having low socioeconomic status, those living in remote or rural areas, are often recognised as bearing an unequal burden of illness in society. This paper aims to examine equity of utilisation of general practitioner services in Australia.