Indigenous Genetics and Rare Diseases: Harmony, Diversity and Equity.

Advances in our understanding of genetic and rare diseases are changing the face of healthcare. Crucially, the global community must implement these advances equitably to reduce health disparities, including between Indigenous and non-Indigenous peoples. We take an Australian perspective to illustrate some key areas that are fundamental to the equitable translation of new knowledge for the improved diagnosis of genetic and rare diseases for Indigenous people. Specifically, we focus on inequalities in access to clinical genetics services and the lack of genetic and phenomic reference data to inform diagnoses. We provide examples of ways in which these inequities are being addressed through Australian partnerships to support a harmonious and inclusive approach to ensure that benefits from traditional wisdom, community knowledge and shared experiences are interwoven to support and inform implementation of new knowledge from genomics and precision public health. This will serve to deliver benefits to all of our diverse citizens, including Indigenous populations.

The diagnostic odyssey: insights from parents of children living with an undiagnosed condition.

BACKGROUND: People living with rare disease often have protracted journeys towards diagnosis. In the last decade, programs have arisen around the world that are dedicated to ending this 'diagnostic odyssey', including the Undiagnosed Diseases Program Western Australia (UDP-WA), which has a focus on finding diagnoses for children and young adults. To explore the lived experience of the diagnostic journey semi-structured interviews were conducted with parents of 11 children at commencement of their involvement in the UDP-WA. RESULTS: Thematic analysis revealed three main themes that captured parents' experiences and perspectives. Parents reported (i) the need to respond to significant care needs of their children, which span not only the health system but other systems such as education and disability services. In doing so, parents become the navigator, expert and advocate for their children. Meanwhile, parents are on (ii) the diagnostic odyssey-the rollercoaster of their journey towards diagnosis, which includes various names applied to their child's condition, and the impact of no diagnosis. Parents described their views on (iii) the value of a diagnosis and the outcomes they expect to be associated with a diagnosis. CONCLUSION: Analysis showed an overall significant perceived value of a diagnosis. Our study provides new perspectives on the concept of diagnosis and indicates that parents may benefit from supports for their child's care needs that are beyond the scope of the UDP-WA.

SMART Work Design: Accelerating the Diagnosis of Rare Diseases in the Western Australian Undiagnosed Diseases Program.

The accurate and efficient diagnosis of rare diseases, many of which include congenital anomalies, depends largely on the specialists who diagnose them - including their ability to work alongside specialists from other fields and to take full advantage of cutting-edge precision medicine technologies and precision public health approaches. However, highly specialized clinicians operating within a historically-siloed healthcare system is antithetical to the multi-disciplinary, collaborative, and creative approach that facilitates the diagnosis of rare diseases. The Western Australian Undiagnosed Diseases Program (UDP-WA) successfully re-designed the work of the involved clinicians to facilitate teamworking across silos. To understand the effectiveness of the Western Australian program, we draw on a SMART work design perspective (i.e., work that involves Stimulation, Mastery, Agency, Relations, and Tolerable demands). We propose that the redesign was successful in part because it improved crucial psychosocial work characteristics that are less prevalent in the broader work system, as identified in the SMART model. Based on the effectiveness of UDP-WA and its SMART design, we provide a framework that clinicians, healthcare managers, and policymakers can consider when they re-design work so that they can create SMART jobs within healthcare.

Identifying Perceptions and Preferences of the General Public Concerning Universal Screening of Children for Familial Hypercholesterolaemia.

BACKGROUND/AIMS: Familial hypercholesterolaemia (FH) is a common genetic disorder that, if untreated, predisposes individuals to premature coronary heart disease. As most individuals with FH remain undiagnosed, new approaches to detection are needed and should be considered a priority in public health genomics. Universal screening of children for FH has been proposed, and this study explores public perspectives on the acceptability of this approach. METHODS: A one-day deliberative public forum was held in Perth, WA, Australia. Thirty randomly selected individuals were recruited, with self-reported sociodemographic characteristics used to obtain discursive representation. Participants were presented with information from a variety of perspectives and asked to discuss the information provided to identify points of consensus and disagreement. The data collected were analysed using thematic analysis. RESULTS: Of the 17 participants at the forum, 16 deemed universal screening of children for FH to be acceptable. Fifteen of these 16 believed this was best performed at the time of an immunisation. Participants proposed a number of conditions that should be met to reduce the likelihood of unintended harm resulting from the screening process. DISCUSSION/CONCLUSION: The outcomes of the forum suggest that establishing a universal screening programme for FH in childhood is acceptable to the general public in WA.

3-Dimensional Facial Analysis-Facing Precision Public Health.

Precision public health is a new field driven by technological advances that enable more precise descriptions and analyses of individuals and population groups, with a view to improving the overall health of populations. This promises to lead to more precise clinical and public health practices, across the continuum of prevention, screening, diagnosis, and treatment. A phenotype is the set of observable characteristics of an individual resulting from the interaction of a genotype with the environment. Precision (deep) phenotyping applies innovative technologies to exhaustively and more precisely examine the discrete components of a phenotype and goes beyond the information usually included in medical charts. This form of phenotyping is a critical component of more precise diagnostic capability and 3-dimensional facial analysis (3DFA) is a key technological enabler in this domain. In this paper, we examine the potential of 3DFA as a public health tool, by viewing it against the 10 essential public health services of the "public health wheel," developed by the US Centers for Disease Control. This provides an illustrative framework to gage current and emergent applications of genomic technologies for implementing precision public health.

Initiating an undiagnosed diseases program in the Western Australian public health system.

BACKGROUND: New approaches are required to address the needs of complex undiagnosed diseases patients. These approaches include clinical genomic diagnostic pipelines, utilizing intra- and multi-disciplinary platforms, as well as specialty-specific genomic clinics. Both are advancing diagnostic rates. However, complementary cross-disciplinary approaches are also critical to address those patients with multisystem disorders who traverse the bounds of multiple specialties and remain undiagnosed despite existing intra-specialty and genomic-focused approaches. The diagnostic possibilities of undiagnosed diseases include genetic and non-genetic conditions. The focus on genetic diseases addresses some of these disorders, however a cross-disciplinary approach is needed that also simultaneously addresses other disorder types. Herein, we describe the initiation and summary outcomes of a public health system approach for complex undiagnosed patients - the Undiagnosed Diseases Program-Western Australia (UDP-WA). RESULTS: Briefly the UDP-WA is: i) one of a complementary suite of approaches that is being delivered within health service, and with community engagement, to address the needs of those with severe undiagnosed diseases; ii) delivered within a public health system to support equitable access to health care, including for those from remote and regional areas; iii) providing diagnoses and improved patient care; iv) delivering a platform for in-service and real time genomic and phenomic education for clinicians that traverses a diverse range of specialties; v) retaining and recapturing clinical expertise; vi) supporting the education of junior and more senior medical staff; vii) designed to integrate with clinical translational research; and viii) is supporting greater connectedness for patients, families and medical staff. CONCLUSION: The UDP-WA has been initiated in the public health system to complement existing clinical genomic approaches; it has been targeted to those with a specific diagnostic need, and initiated by redirecting existing clinical and financial resources. The UDP-WA supports the provision of equitable and sustainable diagnostics and simultaneously supports capacity building in clinical care and translational research, for those with undiagnosed, typically rare, conditions.