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BackgroundConsumer engagement is increasingly recognized as an instrumental component of health research, with many institutions and international bodies mandating it as part of the research and funding process. Given an increasing utilization of consumer engagement in health research, it is critical to identify the literature which support its value and tools that capture successful outcomes. To develop an overview of the literature, we conducted an umbrella scoping review exploring important outcomes of consumer engagement in health research combined with a scoping review of relevant frameworks. Specifically, we aimed to capture outcomes which reflect authentic and meaningful consumer engagement.MethodsFour databases (PubMed, Embase, CINAHL and Cochrane Library) were searched using key search terms. Records were included if they were review articles or frameworks that addressed outcomes of consumer engagement in health research. Data was analyzed using descriptive statistics and an inductive qualitative content analysis. Identified outcomes were sorted based on the three most relevant stakeholder groups (consumer, researcher, institution).ResultsA total of twenty articles that explored a variety of health disciplines were included. We identified fifteen measurable outcomes of consumer engagement in health research. Eight core outcomes were relevant to all stakeholder groups, and were considered fundamental to authentic consumer engagement including (1) trust, (2) empowerment, (3) respect, (4) confidence in the outcomes of the research, (5) transparency of the research process, (6) satisfaction with the consumer engagement program, (7) knowledge and experiences of consumers, and (8) degree of consumer engagement. Outcomes pertaining to specific stakeholder groups included representativeness and diversity of the consumer groups, research relevance to consumers, funding opportunities, quality/validity of the research, recruitment/retention rates, translation and dissemination of research, and interpretation of results.ConclusionThis review identified key measurable outcomes that could be captured when evaluating the impacts of consumer engagement on health research and the success of consumer engagement programs. All outcomes identified were relatively underexplored within the literature, and inadequately and/or inconsistently evaluated amongst studies. Future research should consult all stakeholder groups to identify outcomes perceived to be reflective of optimal consumer engagement.

Background: Melanoma genetic testing reportedly increases preventative behaviour without causing psychological harm. Genetic testing for familial melanoma risk is now available, yet little is known about dermatologists’ perceptions regarding the utility of testing and genetic testing ordering behaviours.Objectives: To survey Australasian Dermatologists on the perceived utility of genetic testing, current use in practice, as well as their confidence and preferences for the delivery of genomics education.Methods: A 37-item survey, based on previously validated instruments, was sent to accredited members of the Australasian College of Dermatologists in March 2021. Quantitative items were analysed statistically, with one open-ended question analysed qualitatively. Results: The response rate was 56% (256/461), with 60% (153/253) of respondents between 11 and 30 years post-graduation. While 44% (112/252) of respondents agreed, or strongly agreed, that genetic testing was relevant to their practice today, relevance to future practice was reported significantly higher at 84% (212/251) (t = -9.82, p < 0.001). Ninety three percent (235/254) of respondents reported rarely or never ordering genetic testing. Dermatologists who viewed genetic testing as relevant to current practice were more likely to have discussed (p < 0.001) and/or offered testing (p < 0.001). Respondents indicated high confidence in discussing family history of melanoma, but lower confidence in ordering genetic tests and interpreting results. Eighty four percent (207/247) believed that genetic testing could negatively impact life insurance, while only 26% (63/244) were aware of the moratorium on using genetic test results in underwriting in Australia. A minority (22%, 55/254) reported prior continuing education in genetics. Face-to-face courses were the preferred learning modality for upskilling.Conclusion: Australian Dermatologists widely recognise the relevance of genetic testing to future practice, yet few currently order genetic tests. Future educational interventions could focus on how to order appropriate genetic tests and interpret results, as well as potential implications on insurance.

Consumer and community engagement (CCE) in the implementation of genomics into health services and associated research is needed to ensure that changes benefit the affected patients. Queensland Genomics was a program to implement genomics into a public health service. We describe its Community Advisory Group’s (CAG) structure and function and provide recommendations based on the CAG members’ perspectives. The CAG provided advice to the Queensland Genomics program and its projects in an advisory capacity. The CAG was also resourced to develop and lead community-focused activities. Key enablers for CAG included; diversity of CAG members’ skills and experience, adequate resourcing, and the CAG’s ability to self-determine their direction. The CAG experienced limitations due to a lack of mechanisms to implement CCE in the Program’s projects. Here, we provide insights and commentary on this CAG, which will be useful for other initiatives seeking to undertake CCE in genomic research and health care.

Abstract Background Clinical whole exome sequencing was introduced in an Australian centre in 2017, as an alternative to Sanger sequencing. We aimed to identify predictors of cancer physicians’ somatic mutation test ordering behaviour. Methods A validated instrument assessed somatic mutation test ordering, genomic confidence, perceived utility of tumour molecular profiling, and percent of patients eligible for targeted therapy. A cash incentive was included in 189/244 questionnaires which were mailed to all Queensland cancer specialists in November 2018. Results 110 participated (response rate 45%); 54.7% oncologists, and the remainder were surgeons, haematologists and pulmonologists. Oncologists were more likely to respond (p = 0.008), and cash incentive improved the response rate (p

Health Interpreters enable effective communication between health practitioners and patients with limited knowledge of the predominant language. This study developed and evaluated a training session introducing Health Interpreters to genetics. The online training was delivered multiple times as a single 2-h session comprising lectures and activities. Participants completed questionnaires (pre-, post-, and 6-months follow-up) to assess the impact of training on knowledge, attitude, self-efficacy, and self-reported practice behaviour. Questionnaires were analysed using descriptive statistics, Fisher’s Exact, or independent t-test. In total, 118 interpreters participated in the training sessions. Respondent knowledge improved, with gains maintained at 6-months (p < 0.01). There were no changes in self-efficacy, and attitudes. Training did not change self-reported practice behaviour, but there was notable pre-existing variability in participants’ methods of managing unknown genetic words. Most respondents agreed that training was useful (93%) and relevant (79%) to their work. More respondents reported learning more from the case study activity (86%) than the group activity (58%). Health Interpreters found the training acceptable and demonstrated sustained improvement in knowledge of genetic concepts. Increased delivery of this training and associated research is needed to assess findings in a larger cohort and to measure the impact on patients.

Introduction Genetic testing for hereditary cancers can improve long-term health outcomes through identifying high-risk individuals and facilitating targeted prevention and screening/surveillance. The rising demand for genetic testing exceeds the clinical genetic workforce capacity. Therefore, non-genetic specialists need to be empowered to offer genetic testing. However, it is unknown whether patient outcomes differ depending on whether genetic testing is offered by a genetics specialist or a trained non-genetics clinician. This paper describes a protocol for upskilling non-genetics clinicians to provide genetic testing, randomise high-risk individuals to receive testing from a trained clinician or a genetic counsellor, and then determine whether patient outcomes differed depending on provider-type. Methods An experiential training program to upskill dermatologically-trained clinicians to offer genetic testing for familial melanoma is being piloted on 10–15 clinicians, prior to wider implementation. Training involves a workshop, comprised of a didactic learning presentation, case studies, simulated sessions, and provision of supporting documentation. Clinicians later observe a genetic counsellor led consultation before being observed leading a consultation. Both sessions are followed by debriefing with a genetic counsellor. Thereafter, clinicians independently offer genetic testing in the clinical trial. Individuals with a strong personal and/or family history of melanoma are recruited to a parallel-group trial and allocated to receive pre- and post- genetic testing consultation from a genetic counsellor, or a dermatologically-trained clinician. A mixed method approach measures psychosocial and behavioural outcomes. Longitudinal online surveys are administered at five timepoints from baseline to one year post-test disclosure. Semi-structured interviews with both patients and clinicians are qualitatively analysed. Significance This is the first program to upskill dermatologically-trained clinicians to provide genetic testing for familial melanoma. This protocol describes the first clinical trial to compare patient-reported outcomes of genetic testing based on provider type (genetic counsellors vs trained non-genetic clinicians).

Precision prevention of advanced melanoma is fast becoming a realistic prospect, with personalized, holistic risk stratification allowing patients to be directed to an appropriate level of surveillance, ranging from skin self-examinations to regular total body photography with sequential digital dermoscopic imaging. This approach aims to address both underdiagnosis (a missed or delayed melanoma diagnosis) and overdiagnosis (the diagnosis and treatment of indolent lesions that would not have caused a problem). Holistic risk stratification considers several types of melanoma risk factors: clinical phenotype, comprehensive imaging-based phenotype, familial and polygenic risks. Artificial intelligence computer-aided diagnostics combines these risk factors to produce a personalized risk score, and can also assist in assessing the digital and molecular markers of individual lesions. However, to ensure uptake and efficient use of AI systems, researchers will need to carefully consider how best to incorporate privacy and standardization requirements, and above all address consumer trust concerns.

Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic disorders of impaired pancreatic β cell function. The mechanisms underlying MODY include β cell KATP channel dysfunction (e.g., KCNJ11 [MODY13] or ABCC8 [MODY12] mutations); however, no other β cell channelopathies have been associated with MODY to date. Here, we have identified a nonsynonymous coding variant in KCNK16 (NM_001135105: c.341T>C, p.Leu114Pro) segregating with MODY. KCNK16 is the most abundant and β cell–restricted K+ channel transcript, encoding the two-pore-domain K+ channel TALK-1. Whole-cell K+ currents demonstrated a large gain of function with TALK-1 Leu114Pro compared with TALK-1 WT, due to greater single-channel activity. Glucose-stimulated membrane potential depolarization and Ca2+ influx were inhibited in mouse islets expressing TALK-1 Leu114Pro with less endoplasmic reticulum Ca2+ storage. TALK-1 Leu114Pro significantly blunted glucose-stimulated insulin secretion compared with TALK-1 WT in mouse and human islets. These data suggest that KCNK16 is a previously unreported gene for MODY.

There have been two major eras in the history of gene discovery. The first was the era of linkage analysis, with approximately 1,300 disease-related genes identified by positional cloning by the turn of the millennium. The second era has been powered by two major breakthroughs: the publication of the human genome and the development of massively parallel sequencing (MPS). MPS has greatly accelerated disease gene identification, such that disease genes that would have taken years to map previously can now be determined in a matter of weeks. Additionally, the number of affected families needed to map a causative gene and the size of such families have fallen: de novo mutations, previously intractable by linkage analysis, can be identified through sequencing of the parent–child trio, and genes for recessive disease can be identified through MPS even of a single affected individual. MPS technologies include whole exome sequencing (WES), whole genome sequencing (WGS), and panel sequencing, each with their strengths. While WES has been responsible for most gene discoveries through MPS, WGS is superior in detecting copy number variants, chromosomal rearrangements, and repeat-rich regions. Panels are commonly used for diagnostic purposes as they are extremely cost-effective and generate manageable quantities of data, with no risk of unexpected findings. However, in instances of diagnostic uncertainty, it can be challenging to choose the right panel, and in these circumstances WES has a higher diagnostic yield. MPS has ethical, social, and legal implications, many of which are common to genetic testing generally but amplified due to the magnitude of data (e.g., relationship misattribution, identification of variants of uncertain significance, and genetic discrimination); others are unique to WES and WGS technologies (e.g., incidental or secondary findings). Nonetheless, MPS is rapidly translating into clinical practice as an extremely useful part of the clinical armamentarium.

As genetic testing becomes increasingly utilized in health care, consumer awareness and understanding is critical. Both are reported to be low in Australia, though there are limited studies to date. A consumer survey assessed perceived knowledge, awareness and attitudes toward genetic medicine, prior to consumers’ genomics forums in Queensland in 2018 and 2019. Data was analyzed using t-test and Mann-Whitney U tests analysis to detect any associations between sociodemographic factors and familiarity or attitudes. This highly educated and experienced health consumer cohort reported they were significantly more familiar with the healthcare system generally than genetic medicine specifically (p < 0.0001). Consumers perceived that genetic testing would be significantly more important in the future than it is currently (p < 0.00001). Consumers agreed that genetic testing should be promoted (91.4%), made available (100%), better funded (94.2%), and offered to all pregnant women (81.6%). The preferred learning modality about genetics was internet sites (62.7%) followed by talks/presentations (30.8%). Benefits of genetic testing, reported in qualitative responses, included the potential for additional information to promote personal control and improve healthcare. Perceived concerns included ethical implications (including privacy and discrimination), and current limitations of science, knowledge and/or practice. This study demonstrates that even knowledgeable consumers have little familiarity with genetic medicine but are optimistic about its potential benefits. Ethical concerns, particularly concerns regarding genetic discrimination should inform legislation and policy. Consumers are supportive of online resources in increasing genomic literacy.

Causal attributions are important determinants of how health threats are processed and affect health-related behaviors. To date, there has been no research on causal attributions in genetic conditions in Aboriginal Australians. Forty members of a large Aboriginal Australian family with Marfan syndrome (MFS) were invited to participate in an ethically approved study exploring causal attributions, including perceived causes of phenotypic variability within the family. Eighteen individuals consented to conduct semi-structured qualitative interviews, which were recorded, transcribed verbatim and analyzed thematically. Most participants knew that MFS was genetic, but there were diverse theories about inheritance, including beliefs that it skipped generations, was affected by birth order and/or gender, and that it co-occurred with inheritance of blue eyes within this family. The mutation was thought to have been inherited from British settlers and initially triggered by disease or diet. Factors believed to modify disease severity included other genes and lifestyle factors, particularly alcohol and substance abuse and stress. Generally, this family did not endorse “blaming” chance or a higher power for phenotypic variability, though some felt that the spirits or a deity may have played a role. In conclusion, although participants knew MFS was a genetic condition, many speculated about the role of non-genetic causes in initiating the original mutation; and the gene-environment interaction was thought to affect severity. This study demonstrates a successful approach for exploring causal attributions in other genetic conditions in First Australians.

Abstract Background Marfan syndrome (MFS) is a dominant monogenic disorder caused by mutations in fibrillin 1 (FBN1). Rarely, compound heterozygosity for FBN1 mutations has been described. Methods A large kindred with MFS was assessed clinically over decades, and genetically using exome and/or Sanger sequencing. Results A previously identified FBN1 missense variant (p.Tyr754Cys) was confirmed in all subjects with MFS. An additional variant (p.Met2273Thr), previously associated with incomplete MFS, was identified in three siblings. These three compound heterozygous individuals had aortic dilatation at early age (all 40 years but not requiring surgical intervention. Another heterozygous (p.Tyr754Cys) sibling did require aortic root repair (28 years). The heterozygous (p.Met2273Thr) mother had aortic dilatation diagnosed at age 68 years but has not required surgical repair. Conclusion Although compound heterozygosity or homozygosity is rare in MFS, it should be considered when there is an unusually severe phenotype in a subset of family members.

Introduction Primary ciliary dyskinesia (PCD) is a rare, progressive, inherited ciliopathic disorder, which is incurable and frequently complicated by the development of bronchiectasis. There are few randomised controlled trials (RCTs) involving children and adults with PCD and thus evidence of efficacy for interventions are usually extrapolated from people with cystic fibrosis. Our planned RCT seeks to address some of these unmet needs by employing a currently prescribed (but unapproved for long-term use in PCD) macrolide antibiotic (azithromycin) and a novel mucolytic agent (erdosteine). The primary aim of our RCT is to determine whether regular oral azithromycin and erdosteine over a 12-month period reduces acute respiratory exacerbations among children and adults with PCD. Our primary hypothesis is that: people with PCD who regularly use oral azithromycin and/or erdosteine will have fewer exacerbations than those receiving the corresponding placebo medications. Our secondary aims are to determine the effect of the trial medications on PCD-specific quality-of-life (QoL) and other clinical outcomes (lung function, time-to-next exacerbation, hospitalisations) and nasopharyngeal bacterial carriage and antimicrobial resistance.Methods and analysis We are currently undertaking a multicentre, double-blind, double-dummy RCT to evaluate whether 12 months of azithromycin and/or erdosteine is beneficial for children and adults with PCD. We plan to recruit 104 children and adults with PCD to a parallel, 2×2 partial factorial superiority RCT at five sites across Australia. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, lung function and nasopharyngeal carriage by respiratory bacterial pathogens and their associated azithromycin resistance.Ethics and dissemination Our RCT is conducted in accordance with Good Clinical Practice and the Australian legislation and National Health and Medical Research Council guidelines for ethical conduct of Research, including that for First Nations Australians.Trial registration number ACTRN12619000564156.

Introduction Melanoma is Australia’s fourth most common cancer. Early detection is fundamental in maximising health outcomes and minimising treatment costs. To date, population-based screening programmes have not been justified in health economic studies. However, a skin surveillance approach targeting high-risk individuals could improve the cost-benefit ratio.Methods and analysis This paper describes a 2-year longitudinal randomised controlled trial (RCT) to compare routine clinical care (control) with an intensive skin surveillance programme (intervention) consisting of novel three-dimensional (3D) total-body photography (TBP), sequential digital dermoscopy and melanoma-risk stratification, in a high-risk melanoma cohort. Primary outcomes will evaluate clinical, economic and consumer impact of the intervention. Clinical outcomes will evaluate differences in the rate of lesion excisions/biopsies per person, benign to malignant ratio for excisions and thickness of melanomas diagnosed. A health economic analysis using government data repositories will capture healthcare utilisation and costs relating to skin surveillance. Consumer questionnaires will examine intervention acceptability, the psychological impact, and attitudes towards melanoma risk and sun protective behaviour. Secondary outcomes include the development of a holistic risk algorithm incorporating clinical, phenotypic and genetic factors to facilitate the identification of those most likely to benefit from this surveillance approach. Furthermore, the feasibility of integrating the intervention with teledermatology to enhance specialist care in remote locations will be evaluated. This will be the first RCT to compare a targeted surveillance programme utilising new 3D TBP technology against current routine clinical care for individuals at high risk of melanoma.Ethics and dissemination This study has received Human Research Ethics Committee (HREC) approval from both Metro South Health HREC (HREC/17/QPAH/816) and The University of Queensland HREC (2018000074).Trial registration number ANZCTR12618000267257; Pre-results.

IntroductionGenetic testing for hereditary cancers can improve long-term health outcomes through identifying high-risk individuals and facilitating targeted prevention and screening/surveillance. The rising demand for genetic testing exceeds the clinical genetic workforce capacity. Therefore, non-genetic specialists need to be empowered to offer genetic testing. However, it is unknown whether patient outcomes differ depending on whether genetic testing is offered by a genetics specialist or a trained non-genetics clinician. This paper describes a protocol for upskilling non-genetics clinicians to provide genetic testing, randomise high-risk individuals to receive testing from a trained clinician or a genetic counsellor, and then determine whether patient outcomes differed depending on provider-type.MethodsAn experiential training program to upskill dermatologically-trained clinicians to offer genetic testing for familial melanoma is being piloted on 10-15 clinicians, prior to wider implementation. Training involves a workshop, comprised of a didactic learning presentation, case studies, simulated sessions, and provision of supporting documentation. Clinicians later observe a genetic counsellor led consultation before being observed leading a consultation. Both sessions are followed by debriefing with a genetic counsellor. Thereafter, clinicians independently offer genetic testing in the clinical trial. Individuals with a strong personal and/or family history of melanoma are recruited to a parallel-group trial and allocated to receive pre- and post- genetic testing consultation from a genetic counsellor, or a dermatologically-trained clinician. A mixed method approach measures psychosocial and behavioural outcomes. Longitudinal online surveys are administered at five timepoints from baseline to one year post-test disclosure. Semi-structured interviews with both patients and clinicians are qualitatively analysed.SignificanceThis is the first program to upskill dermatologically-trained clinicians to provide genetic testing for familial melanoma. This protocol describes the first clinical trial to compare patient-reported outcomes of genetic testing based on provider type (genetic counsellors vs trained non-genetic clinicians).

Amelanotic/hypomelanotic melanoma is a clinicopathologic subtype with absent or minimal melanin. This study assessed previously reported coding variants in albinism genes (TYR, OCA2, TYRP1, SLC45A2, SLC24A5, LRMDA) and common intronic, regulatory variants of OCA2 in individuals with amelanotic/hypomelanotic melanoma, pigmented melanoma cases and controls. Exome sequencing was available for 28 individuals with amelanotic/hypomelanotic melanoma and 303 individuals with pigmented melanoma, which were compared to whole exome data from 1144 Australian controls. Microarray genotyping was available for a further 17 amelanotic/hypomelanotic melanoma, 86 pigmented melanoma, 147 melanoma cases (pigmentation unknown) and 652 unaffected controls. Rare deleterious variants in TYR/OCA1 were more common in amelanotic/hypomelanotic melanoma cases than pigmented melanoma cases (set mixed model association tests P = 0.0088). The OCA2 hypomorphic allele p.V443I was more common in melanoma cases (1.8%) than controls (1.0%, X2 P = 0.02), and more so in amelanotic/hypomelanotic melanoma (4.4%, X2 P = 0.007). No amelanotic/hypomelanotic melanoma cases carried an eye and skin darkening haplotype of OCA2 (including rs7174027), present in 7.1% of pigmented melanoma cases (P = 0.0005) and 9.4% controls. Variants in TYR and OCA2 may play a role in amelanotic/hypomelanotic melanoma susceptibility. We suggest that somatic loss of function at these loci could contribute to the loss of tumor pigmentation, consistent with this we found a higher rate of somatic mutation in TYR/OCA2 in amelanotic/hypomelanotic melanoma vs pigmented melanoma samples (28.6% vs 3.0%; P = 0.021) from The Cancer Genome Atlas Skin Cutaneous Melanoma collection.