Associations between Multiple Health Indicators and Carotid Artery Intima-Media Thickness in A Healthy and Active Elderly Population.

The purpose of this study was to examine correlations between health indicators (age, BMI, blood pressure (BP), functional strength (FS), handgrip strength, and predicted VO2 max) and carotid intima-media thickness (cIMT) in an active 50 years+ population. Study participants' mean cIMT was also compared to the cIMT mean of the general population. Health screenings were conducted on 1818 participants at the Huntsman World Senior Games from 2016 to 2019. Pearson's correlations, Spearman's correlations, and ANOVA were performed using SPSS. Weak but significant correlations were evident between cIMT and age (r = 0.283, p < 0.001), systolic BP (r = 0.253, p = 0.001), diastolic BP (r = 0.074, p = 0.016), weight (r = 0.170, p < 0.001), height (r = 0.153, p < 0.001), handgrip L (r = 0.132, p < 0.001), handgrip R (r = 0.074, p < 0.029), and BMI (r = 0.07, p = 0.029); non-significant correlations were evident with predicted VO2 max (r = -0.035, p = 0.382), and FS (r = -0.025, p = 0.597). When controlling for age, systolic BP, and sex, only handgrip L (r = 0.225, p = 0.014) was significantly correlated with cIMT. Mean cIMT for this cohort was lower across all sexes and age-matched groups (cIMT = 0.6967 mm (±0.129)). Physical activity is linked to reduced cIMT. Most health-related indicators in this study were significantly but weakly correlated with cIMT. Additional research is needed before common indicators can be used as a surrogate for cIMT and CVD risk. Results from this study can provide clinicians with additional information to reduce CVD risk through modifiable risk factors. Classic CVD risk factors such as systolic BP and BMI should be considered in patients regardless of lifestyle.

The relationship between patient volume and mortality in NSW major trauma service hospitals.

INTRODUCTION: Conventional wisdom is that Major Trauma Services (MTS) treating larger volumes of severe trauma patients will have better outcomes than lower volume centres, but recent studies from Europe have questioned this relationship. We aimed to determine if there is a relationship between patient volume and outcome in New South Wales (NSW) MTS hospitals. MATERIALS AND METHODS: Retrospective observational study using data from the NSW State Trauma Registry from 2010 to 2019 inclusive. Adult patients with Injury Severity Score >15 transported directly to a NSW MTS were included. Outcome measures were mortality at hospital discharge, and intensive care unit and hospital length of stay. Generalised estimating equation models were created to determine the adjusted relationship between patient volume and the main outcome measures. RESULTS: The mean annual patient volume of the MTS ranged from 127.4 to 282.0 patients whilst the observed mortality rates p.a. ranged from 10.4 % to 17.19 %. Multivariate analysis, using low volume MTS as the reference, did not demonstrate a significant difference in mortality between high and low volume MTS (adjusted OR: 1.14 95 % CI: 0.98-1.25, P = 0.087). There was however a significant correlation between volume and length of hospital stay (adjusted ß; 0.024, 95 % CI, 0.182 - 1.089, P = 0.006). CONCLUSIONS: There was no mortality difference between high and low volume MTS demonstrated. Length of hospital stay significantly increased with increasing volume however.

Bidirectional association between breast cancer and meningioma: a systematic review and meta-analysis.

BACKGROUND: An association between breast cancer and meningioma has been suggested in cohort studies. We aimed to perform a systematic review and meta-analysis to determine whether there is an association between initial breast cancer and subsequent meningioma diagnosis and vice versa. METHODS: A systematic literature search was performed on Medline, Embase, Scopus and Google scholar from inception up to April 2023. A meta-analysis of selected studies was performed using Review Manager 5.4. RESULTS: There were eight studies included in the systematic review. Seven had reported Standardized Incidence Ratio (SIR) for female patients and were suitable for the meta-analysis. Only one study reported SIR for male patients. For the association between initial breast cancer and subsequent meningioma, in 795 000 female patients with follow-up ranging from 7 to 13 years, the SIR was 1.27 (95% CI: 1.20-1.34, P-value <0.00001). For the association between initial meningioma and subsequent breast cancer, in 28 000 female patients with follow-up ranging from 6 to 15 years, the SIR was 1.32 (95% CI: 1.21-1.45, P-value <0.00001). There were low heterogeneity and no significant publication bias. CONCLUSION: There was a small but significant association between initial breast cancer and subsequent meningioma as well as initial meningioma and subsequent breast cancer in female patients. The potential underlying mechanisms and risk factors were unclear from current literature and would be a potential area for future research.

Students' perceived research skills development and satisfaction after completion of a mandatory research project: results from five cohorts of the Sydney medical program.

BACKGROUND: Research activities undertaken during University studies contribute to preparation of medical students for practice of evidence-based medicine. This study aimed to understand medical students' experiences, perceived research skills development and satisfaction associated with completion of mandatory research projects. METHODS: An online survey was sent to five cohorts of students (n = 1375) from years 2017-2021 at the completion of their research projects. Univariate analysis was conducted to understand students' perception of research skills development, followed by linear regression modeling to explore factors influencing satisfaction with their research project. Manifest content analysis employing a framework approach was used to analyse qualitative data from responses to open ended questions. RESULTS: Response rate was 42%, with 513 (89%) returned surveys being complete and included in analysis. Whilst 37% of students felt they had requisite research skills before undertaking the research project, 84% reported they had these skills after completing the project (χ2 = 8.99, P = 0.02). Mean satisfaction score of the students was 5.0/10 (+/- 2.5, median = 6 (IQR = 3.0-7.0) with 59% of students reporting satisfaction scores higher than the average. Higher satisfaction scores were reported by those who perceived that: research methods and teaching was useful in preparing them for conducting research; the research project helped them acquire new skills; the project resulted in peer-reviewed publication; and, who felt supported by their supervisors. Responses to open ended questions offered important insights into student experience and emphasised the importance of supportive supervisors and the need for a dedicated research block in the busy medical program. CONCLUSIONS: The majority of students reported positive outcomes from the mandatory research project. Student satisfaction can be improved by ensuring supportive research environments and high-quality supervision, and inclusion of dedicated research time in the medical curriculum.

Cardiovascular Outcomes of Differentiated Thyroid Cancer Patients on Long Term TSH Suppression: A Systematic Review and Meta-Analysis.

We performed a systematic review and meta-analysis of the literature regarding cardiovascular outcomes of differentiated thyroid cancer (DTC) patients who are on long term thyroid stimulating hormone suppression. Searches were carried out using Prisma guidelines in Medline, Embase, CENTRAL, CINAHL and Scopus databases. Eligible papers were those which investigated discrete cardiovascular clinical outcomes in TSH suppressed patients and meta-analysis of selected studies was performed using Revman 5.4.1. We found a total of 195 879 DTC patients with median length to follow up of 8.6 years (range 5-18.8 years). Analysis showed DTC patients to be at higher risk of atrial fibrillation (HR 1.58, 95% CI 1.40, 1.77), stroke (HR 1.14, 95% CI 1.09, 1.20) and all-cause mortality (HR 2.04, 95% CI 1.02, 4.07). However, there was no difference in risk of heart failure, ischemic heart disease or cardiovascular mortality. These findings suggest that degree of TSH suppression must be titrated to accommodate risk of cancer recurrence and cardiovascular morbidity.

Rapid Rescoping and Adaptation: An Evaluation of the Impact of COVID-19 on Postgraduate Medical Student Research Projects.

The COVID-19 pandemic has adversely affected tertiary science and medical education, with significant impact on research-related activities. Research projects are a mandatory requirement of the Doctor of Medicine (MD) Program at the University of Sydney, and medical student projects are delivered across multiple sites in metropolitan and rural New South Wales, Australia. Several cohorts of medical students had projects that were affected by COVID-19. The aims of this study were to determine the impact of COVID-19 on medical student research projects and describe the measures taken to rescope projects, to support students in meeting the learning objectives of the program. Mandatory submission statements for all medical student research project scientific reports for 2020-2022 were examined for reports of the effect of COVID-19 on the project, including COVID-19 related delays, downsizing and the need to change research project types. During the study period, a total of 760 student reports were submitted, of which 217 (28.7%) were affected by COVID-19. About 50% were significantly delayed, 30% were downsized, and 6% required completely new projects. Rescoping arrangements implemented facilitated the successful completion of projects. Overall, the final student grades for the research projects were unaffected by COVID-19 or the related project rescoping. Whilst significantly impacted by COVID-19, medical student research projects were completed with provision of appropriate rescoping plans and academic support. Ensuring projects have a documented contingency plan secured projects as the pandemic progressed and will be a useful safeguard for all future project delivery.

Health professionals' role in the transfer of mosaic embryos after preimplantation genetic testing for aneuploidies.

RESEARCH QUESTION: What are health professionals' clinical practices, views and self-rated competencies regarding the transfer of mosaic embryos? DESIGN: This was a cross-sectional study using surveys. RESULTS: Data were collected from the Royal Australian and New Zealand College of Obstetricians and Gynaecologists and the Fertility Society of Australia and New Zealand. Ninety-five responses were analysed and reported. The results show that most health professionals (n = 62) discussed the transfer of mosaic embryos for different reasons and raised concerns regarding various risks. Although many health professionals were unsure whether mosaic embryos should be transferred, they were more inclined to encourage transfer if the scenario involved segmental losses compared with mosaicism involving duplication of the entire chromosome (i.e. trisomy 21) (e.g. OR = 0.21, P < 0.001; OR = 2.78, P = 0.04). The majority of health professionals would inform patients about the mosaicism to facilitate informed decision making. The factor that health professionals identified as most important when discussing the transfer of mosaic embryos was the specific chromosome involved. Different self-rated competencies were found among health professionals with different backgrounds. Geneticists and genetic counsellors had the highest self-rated competencies. CONCLUSIONS: Most health professionals were willing to discuss the mosaicism in the embryo with patients to facilitate informed decision making. However, health professionals' uncertainty towards the transfer of mosaic embryos indicated a lack of a standardized transfer policy. In addition, obstetricians, gynaecologists and those with multiprofessional backgrounds showed deficiencies in several self-rated competencies, suggesting that education targeted to these groups is needed to optimize the quality of care of women considering transfer of mosaic embryos.

Exploring the impact of the reclassification of a hereditary cancer syndrome gene variant: emerging themes from a qualitative study.

The complexity of genetic variant interpretation means that a proportion of individuals who undergo genetic testing for a hereditary cancer syndrome will have their test result reclassified over time. Such a reclassification may involve a clinically significant upgrade or downgrade in pathogenicity, which may have significant implications for medical management. To date, few studies have examined the psychosocial impact of a reclassification in a hereditary cancer syndrome context. To address this gap, semi-structured telephone interviews were performed with eighteen individuals who had a BRCA1, BRCA2 or Lynch syndrome-related (MLH1, MSH2, MSH6 or PMS2) gene variant reclassified. The interviews were analysed utilising an inductive, qualitative approach and emergent themes were identified by thematic analysis. Variable levels of recall amongst participants were found. Common motivations for initial testing included a significant personal and/or family history of cancer and a desire to "find an answer". No individual whose uncertain result was upgraded reported negative psychosocial outcomes; most reported adapting to their reclassified result and appraised their genetic testing experience positively. However, individuals whose likely pathogenic/pathogenic results were downgraded reported feelings of anger, shock and sadness post reclassification, highlighting that additional psychosocial support may be required for some. Genetic counselling issues and recommendations for clinical practice are outlined.

Population-based BRCA1/2 testing programmes are highly acceptable in the Jewish community: results of the JeneScreen Study.

BACKGROUND: Ashkenazi Jewish (AJ) people have a higher incidence of BRCA1/2 pathogenic variants (PVs) than unselected populations. Three BRCA-Jewish founder mutations (B-JFMs) comprise >90% of BRCA1/2 PVs in AJ people. Personal/family cancer history-based testing misses ≥50% of people with B-JFM. METHODS: We compared two population-based B-JFM screening programmes in Australia-using (1) an online tool (Sydney) and (2) in-person group sessions (Melbourne). RESULTS: Of 2167 Jewish people tested (Sydney n=594; Melbourne n=1573), 1.3% (n=28) have a B-JFM, only 2 of whom had a significant cancer family history (Manchester score ≥12). Pretest anxiety scores were normal (mean 9.9±3.5 (6-24)), with no significant post-result change (9.5±3.3). Decisional regret (mean 7.4±13.0 (0-100)), test-related distress (mean 0.8+/2.2 (0-30)) and positive experiences (reverse-scored) (mean 3.4±4.5 (1-20)) scores were low, with no significant differences between Sydney and Melbourne participants. Post-education knowledge was good overall (mean 11.8/15 (±2.9)) and significantly higher in Melbourne than Sydney. Post-result knowledge was the same (mean 11.7 (±2.4) vs 11.2 (±2.4)). Participants with a B-JFM had higher post-result anxiety and test-related distress and lower positive experiences, than those without a B-JFM, but scores were within the normal range. Family cancer history did not significantly affect knowledge or anxiety, or pretest perception of B-JFM or cancer risks. Most participants (93%) were satisfied/very satisfied with the programme. CONCLUSION: Both B-JFM screening programmes are highly acceptable to Australian Jewish communities. The programme enabled identification of several individuals who were previously unaware they have a B-JFM, many of whom would have been ineligible for current criteria-based testing in Australia.

Exploration of decision-making regarding the transfer of mosaic embryos following preimplantation genetic testing: a qualitative study.

STUDY QUESTION: What are patients' reasoning and decisional needs in relation to the transfer of mosaic embryos following preimplantation genetic testing (PGT)? SUMMARY ANSWER: This study identified four themes, which were patients' reasoning behind decision-making, their decisional needs, the influence of the mosaic embryos on the decision-making and the role of health professionals. WHAT IS KNOWN ALREADY: To date, no study has investigated the reasoning of patients behind their decision-making and the influence of mosaic embryos. STUDY DESIGN SIZE DURATION: This is a cross-sectional study using a qualitative approach. Twenty participants were interviewed, and recruitment was ceased when no new information was identified in the data analysis. It ensured a sufficient sample size for a qualitative study. PARTICIPANTS/MATERIALS SETTING METHODS: Participants were females with mosaic embryos. Semi-structured in-depth interviews were conducted via telephone. MAIN RESULTS AND THE ROLE OF CHANCE: Four themes were identified: reasoning behind decision-making, decisional needs, influence of mosaic embryos on decision-making and the role of health professionals. Potential risks of transferring mosaic embryos and prioritization of euploid embryos were the main reasons for not transferring mosaic embryos. A lack of alternatives, perceived benefits and risk tolerance were main reasons for transferring mosaic embryos. Patients reported that information on mosaic embryos, amniocentesis and termination was important to support their decision-making. Unmet needs relating to healthcare services and social support were reported. In addition, having mosaic embryos affected the patients' emotional and behavioural responses, discussions about prenatal testing, attitudes to termination and further IVF cycles and attitudes towards PGT. Health professionals were found to influence the patients' decision-making. LIMITATIONS REASONS FOR CAUTION: Participants were recruited through one clinic, which may limit the transferability of results. Also, patients' experiences in relation to financial aspects of PGT may not be relevant to other jurisdictions due to different healthcare policies. WIDER IMPLICATIONS OF THE FINDINGS: The results may inform how clinicians provide healthcare services based on factors influencing patients' decision-making. Health professionals should be aware of the influence their attitudes can have on patients' decision-making and should present information accordingly. Also, providing all relevant information may help to facilitate informed decision-making. Provision of psychological support from professionals and support groups is also critical during the process of testing and transfer. Patients have educational needs regarding mosaic embryos, and educational resources including decision aids in plain language are needed. STUDY FUNDING/COMPETING INTERESTS: B.M. was funded through a Senior Research Fellowship Level B (ID 1078523) from the National Health and Medical Research Council of Australia. L.C. was supported by a University International Postgraduate Award under the Australian Government Research Training Program (RTP) scholarship. No other funding was received for this study. The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Factors influencing patients' decision-making about preimplantation genetic testing for monogenic disorders.

STUDY QUESTION: What are the roles of individual and interpersonal factors in couples' decision-making regarding preimplantation genetic testing for monogenic disorders (PGT-M)? SUMMARY ANSWER: Couples' decision-making regarding PGT-M was associated with individual and interpersonal factors, that is the perceived consistency of information received, satisfaction with information, self-efficacy (individuals' beliefs in their ability to make decisions), actual knowledge about PGT-M and social support from the partner. WHAT IS KNOWN ALREADY: Various factors have been shown to be associated with decision-making regarding PGT-M. However, PGT-M is experienced at an individual level, and to date, no studies have investigated the roles of the above-mentioned individual and interpersonal factors. STUDY DESIGN, SIZE, DURATION: This is a cross-sectional study with 279 participants. Participants were recruited through IVFAustralia, Sydney Children's Hospital and support groups from May 2020 to November 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were women who had undergone or were considering PGT-M and their partners. Participants were recruited through IVFAustralia, Sydney Children's Hospital and support groups to complete online questionnaires. Decisional regret, decisional satisfaction and decisional conflict were measured as outcome variables. Multiple linear regressions were performed to examine the association between factors and outcome variables. Mann-Whitney U tests were performed to test the differences between participants who had undergone PGT-M and those who were considering PGT-M. MAIN RESULTS AND THE ROLE OF CHANCE: For couples who had undergone PGT-M, decisional regret was significantly negatively associated with perceived consistency of information received (ß = -0.26, P < 0.01), self-efficacy (ß = -0.25, P < 0.01) and actual knowledge about PGT-M (ß = -0.30, P < 0.001), while decisional satisfaction had positive association with satisfaction with information received (ß = 0.37, P < 0.001) and self-efficacy (ß = 0.24, P < 0.05). For couples who were considering PGT-M, decisional conflict was negatively associated with satisfaction with information received (ß = -0.56, P < 0.001). For females who had undergone PGT-M, decisional regret was negatively associated with social support from the partner (ß = -0.35, P < 0.05) in addition to perceived consistency of information received (ß = -0.24, P < 0.05). In this group, decisional satisfaction was positively associated with women's satisfaction with the information received (ß = 0.34, P < 0.01), social support from the partner (ß = 0.26, P < 0.05) and self-efficacy (ß = 0.25, P < 0.05). For females who were considering PGT-M, decisional conflict was negatively associated with satisfaction with the information received (ß = -0.43, P < 0.01) and social support from the partner (ß = -0.30, P < 0.05). This study also identified those aspects of PGT-M that couples felt most concerned about in relation to their decision-making, in particular safety issues such as short- or long-term health problems for the baby and potential harms to the embryos and the mother's health. The likelihood of getting pregnant and having a baby with a genetic condition being tested for were also important in couples' decision-making. LIMITATIONS, REASONS FOR CAUTION: This study assessed the concerns of couples about having a baby with a variety of genetic conditions. However, condition-specific issues might not be covered. Furthermore, social support from the partner was assessed among females only. Male participants' perceived social support from their partner and the association between mutual support and decision-making were not assessed due to the absence of dyadic data. WIDER IMPLICATIONS OF THE FINDINGS: Results highlight the importance of effective patient education on PGT-M and the need to provide high-quality and consistent information in the context of patient-centred care. Patients are likely to benefit from information that addresses their specific concerns in relation to PGT-M. From females' perspective, support from partners is essential, and partners should, therefore, be encouraged to participate in all stages of the decision-making process. Suggestions for future studies were made. STUDY FUNDING/COMPETING INTEREST(S): B.M. was funded through a Senior Research Fellowship Level B (ID 1078523) from the National Health and Medical Research Council of Australia. L.C. was supported by a University International Postgraduate Award under the Australian Government Research Training Program (RTP) scholarship. No other funding was received for this study. The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Research supervisors' views of barriers and enablers for research projects undertaken by medical students; a mixed methods evaluation of a post-graduate medical degree research project program.

BACKGROUND: Medical degree programs use scholarly activities to support development of basic research skills, critical evaluation of medical information and promotion of medical research. The University of Sydney Doctor of Medicine Program includes a compulsory research project. Medical student projects are supervised by academic staff and affiliates, including biomedical science researchers and clinician-academics. This study investigated research supervisors' observations of the barriers to and enablers of successful medical student research projects. METHODS: Research supervisors (n = 130) completed an anonymous, online survey after the completion of the research project. Survey questions targeted the research supervisors' perceptions of barriers to successful completion of projects and sources of support for their supervision of the student project. Data were analysed by descriptive statistics and using manifest content analysis. Further quantitative investigation was made by cross-tabulation according to prior research supervision experience. RESULTS: Research supervisors reported that students needed both generic skills (75%) and research-based skills (71%) to successfully complete the project. The major barrier to successful research projects was the lack of protected time for research activities (61%). The assessment schedule with compulsory progress milestones enabled project completion (75%), and improved scientific presentation (90%) and writing (93%) skills. Supervisors requested further support for their students for statistics (75%), scientific writing (51%), and funding for projects (52%). Prior research supervision experience influenced the responses. Compared to novice supervisors, highly experienced supervisors were significantly more likely to want students to be allocated dedicated time for the project (P < 0.01) and reported higher rates of access to expert assistance in scientific writing, preparing ethics applications and research methodology. Novice supervisors reported higher rates of unexpected project delays and data acquisition problems (P < 0.05). Co-supervision was favoured by experienced supervisors but rejected by novice supervisors. CONCLUSIONS: Both generic and research-related skills were important for medical student research project success. Overall, protected research time, financial and other academic support were identified as factors that would improve the research project program. Prior research supervision experience influences perceptions of program barriers and enablers. These findings will inform future support needs for projects and research supervisor training for the research supervision role.

Perceptions of causal attribution and attitudes to genetic testing among people with schizophrenia and their first-degree relatives.

Rapid advances in the genetics of psychiatric disorders mean that diagnostic and predictive genetic testing for schizophrenia risk may one day be a reality. This study examined how causal attributions for schizophrenia contribute to interest in a hypothetical genetic test. People with schizophrenia and first-degree relatives of people with schizophrenia were recruited through a schizophrenia research bank and mental health organisation. Semi-structured telephone interviews were conducted with 13 individuals with schizophrenia and 8 first-degree relatives. Transcripts were subjected to a qualitative analysis using the thematic analysis framework. Five themes were developed: (i) "It is like a cocktail", with most participants aware that both genetic and environmental factors contributed to causation, and many mentioning the positive impact of genetic causal explanations; (ii) "Knowledge is power" (i.e., in favour of genetic testing); (iii) Genetic testing provides opportunities for early intervention and avoiding triggers, with participants citing a wide range of perceived benefits of genetic testing but few risks; (iv) Views on reproductive genetic testing for schizophrenia risk with a few participants viewing it as "playing God" but not necessarily being against it; and (v) "It snowballs", whereby participants' understanding of genetics was sophisticated with most believing that multiple rather than single genes contributed to schizophrenia. In conclusion, many individuals had a sound understanding of the role of genetic testing if it were to become available, with evidence of insight into the role of multiple genes and the contribution of other risk factors that may interact with any inherited genetic risk.

Decisional needs of patients considering preimplantation genetic testing: a systematic review.

This systematic review reports on the needs and sources of support in patients' decision-making regarding the uptake of preimplantation genetic testing (PGT). Five databases were searched systematically to capture qualitative and quantitative studies. A total of 2336 studies were screened by title and abstract. Twelve studies met the eligibility criteria and reported on 4047 participants. This systematic review shows that patients need information directly relevant to PGT treatment, and information on health care relating to treatment and alternative reproductive options. Information that is too detailed, excessive and contains a large volume of medical terminology can be a barrier to decision-making. Published research suggests that health professionals provide general information on PGT and discuss it in detail only when patients require more information about it. Additionally, studies have shown that patients receive decisional support through mass media, significant persons in their lives and health professionals, whereas referring obstetricians and gynaecologists provided relatively less help compared with other health professionals. This systematic review highlights the importance of developing decision aids that meet patients' decisional needs as indicated in previous studies and that use innovative formats to deliver information. Additionally, given rapid technical developments, a dearth of continuing professional education is available on PGT for clinicians to keep updated.

The Risk-Reducing Effect of Aspirin in Lynch Syndrome Carriers: Development and Evaluation of an Educational Leaflet.

Carriers of germline mutations in genes associated with Lynch syndrome are at increased risk for colorectal, endometrial, ovarian, and other cancers. There is evidence that daily consumption of aspirin may reduce cancer risk in these individuals. There is a need for educational resources to inform carriers of the risk-reducing effects of aspirin or to support decision-making. An educational leaflet describing the risks and benefits of using aspirin as risk-reducing medicine in carriers of Lynch-syndrome-related mutations is developed and pilot tested in 2017. Carriers are ascertained through a familial cancer clinic and surveyed using a mailed, self-administered questionnaire. The leaflet is highly rated for its content, clarity, length, relevance, and visual appeal by more than 70% of the participants. Most participants (91%) report "a lot" or "quite a bit" of improvement in perceived understanding in knowledge about who might benefit from taking aspirin, its benefits, how long to take it, the reduction in bowel cancer risk, and the optimal dosage. A few (14%) participants seek more information on the dosage of aspirin. This leaflet will be useful as an aid to facilitate discussion between patients and their health care professionals about the use of aspirin as a risk-reducing medication.

Stakeholder attitudes towards establishing a national genomics registry of inherited cancer predisposition: a qualitative study.

This study aimed to describe the acceptability and perceived barriers and enablers to establish a national registry targeting carriers of pathogenic variants in cancer susceptibility genes from stakeholders' perspectives. Such a registry may effectively target carriers to translate existing research findings into optimised clinical care and provide a population-level resource for further clinical research and new gene and therapy discovery. In-depth interviews were conducted with individuals from four stakeholder groups: carriers of pathogenic variants, healthcare professionals, data custodians from the field of familial cancer, and heads of molecular pathology laboratories. Interview data were subjected to a qualitative analysis guided by a thematic analysis framework using NVivo software. A total of 28 individuals were interviewed: 11 carriers, 8 healthcare professionals, 5 laboratory heads, and 4 data custodians. All carriers and healthcare professionals were enthusiastic about the potential research applications of the registry. Carriers described that altruistic motivations provided the foundation of their support of the planned registry. Some carriers felt comfortable with a broad consent (consenting once, prospectively), while others preferred a narrow consent approach (consenting each time data is accessed). Some carriers and data custodians and registry developers also expressed a reluctance to link family member data without appropriate consent. Participants' enthusiasm and support for a national registry herald a productive and responsive research partnership once the registry has been established. Participants' views can be used to inform the approaches to be taken to develop and manage such a registry as an implicit codesign approach.

Polygenic risk in familial breast cancer: Changing the dynamics of communicating genetic risk.

Hereditary breast cancer is associated with known genetic changes: either variants that affect function in a few rare genes or an ever-increasing number of common genomic risk variants, which combine to produce a cumulative effect, known as a polygenic risk (PR) score. While the clinical validity and utility of PR scores are still being determined, the communication of PR is a new challenge for genetic health professionals. This study investigated how PR scores are discussed in the familial cancer clinic compared with a previous study assessing the communication of monogenic risk (MR) for breast cancer. Sixty-five PR consultations between genetic health professionals and women at familial risk of breast cancer were audiotaped, transcribed, and coded using a methodology adapted from the MR study. Analysis of consultations shows that while there were similarities in communicating MR and PR, the complexity and novelty of the polygenic information influenced the style of counseling used by genetic health professionals toward a teaching model of genetic counseling, rather than a patient-centered approach. In particular, compared to MR consultations, in PR consultations significantly fewer counselees (a) were asked about their reasons for attending genetic counseling; or (b) had their information preferences, decision-making style, medical knowledge, understanding, or concerns checked. In conclusion, it is anticipated that PR scores will become part of standard clinical practice. Thus, it will be important for all genetic health professionals to be appropriately educated so that they can tailor their communication to meet patient needs.

Breast cancer polygenic risk scores: a 12-month prospective study of patient reported outcomes and risk management behavior.

PURPOSE: To prospectively assess patient reported outcomes and risk management behavior of women choosing to receive (receivers) or decline (decliners) their breast cancer polygenic risk score (PRS). METHODS: Women either unaffected or affected by breast cancer and from families with no identified pathogenic variant in a breast cancer risk gene were invited to receive their PRS. All participants completed a questionnaire at study enrollment. Receivers completed questionnaires at two weeks and 12 months after receiving their PRS, and decliners a second questionnaire at 12 months post study enrollment. RESULTS: Of the 208 participants, 165 (79%) received their PRS. Among receivers, there were no changes in anxiety or distress following testing. However, compared to women with a low PRS, those with a high PRS reported greater genetic testing-specific distress, perceived risk, decisional regret, and less genetic testing-positive response. At 12 months, breast screening and uptake of risk-reducing strategies were consistent with current Australian guidelines of breast cancer risk management. Reasons for declining PRS included being unable to attend the appointment in person and concerns over potential emotional response. CONCLUSION: The outcomes of the study provide insight into women's responses to receiving PRS and highlight the issues that need to be addressed in the associated model of genetic counseling.

Evaluation of two population screening programmes for BRCA1/2 founder mutations in the Australian Jewish community: a protocol paper.

INTRODUCTION: People of Ashkenazi Jewish (AJ) ancestry are more likely than unselected populations to have a BRCA1/2 pathogenic variant, which cause a significantly increased risk of breast, ovarian and prostate cancer. Three specific BRCA1/2 pathogenic variants, referred to as BRCA-Jewish founder mutations (B-JFM), account for >90% of BRCA1/2 pathogenic variants in people of AJ ancestry. Current practice of identifying eligible individuals for BRCA testing based on personal and/or family history has been shown to miss at least 50% of people who have one of these variants. Here we describe the protocol of the JeneScreen study-a study established to develop and evaluate two different population-based B-JFM screening programmes, offered to people of Jewish ancestry in Sydney and Melbourne, Australia. METHODS AND ANALYSIS: To rmeasure the acceptability of population-based B-JFM screening in Australia, two screening programmes using different methodologies have been developed. The Sydney JeneScreen programme provides information and obtains informed consent by way of an online tool. The Melbourne JeneScreen programme does this by way of community sessions attended in person. Participants complete questionnaires to measure clinical and psychosocial outcomes at baseline, and for those who have testing, 2 weeks postresult. Participants who decline testing are sent a questionnaire regarding reasons for declining. Participants with a B-JFM are sent questionnaires 12-month and 24-month post-testing. The questionnaires incorporate validated scales, which measure anxiety, decisional conflict and regret, and test-related distress and positive experiences, and other items specifically developed or adapted for the study. These measures will be assessed for each programme and the two population-based B-JFM screening methods will be compared. ETHICS AND DISSEMINATION: Institutional Human Research Ethics Committee approval was obtained from the South Eastern Area Health Service Human Research Ethics Committee: HREC Ref 16/125.Following the analysis of the study results, the findings will be disseminated widely through conferences and publications, and directly to participants in writing.

Oncologists' perspectives of telephone genetic counseling to facilitate germline BRCA1/2 testing for their patients with high-grade serous ovarian cancer.

Poly ADP ribose polymerase (PARP) inhibitors offer a survival advantage to women with high-grade serous ovarian cancer who have a germline BRCA1/2 pathogenic variant (PV). Yet, rates of genetic testing among this population have remained persistently low. A national, centralized telephone genetic counseling service was established in January 2016 in Australia to improve access to genetic services and facilitate BRCA1/2 testing for this population to inform treatment. Medical oncologists can refer their patients with high-grade serous ovarian cancer to this service for genetic testing. This study aimed to explore oncologists' experiences of using this telephone genetic counseling service for their patients with high-grade serous ovarian cancer. A qualitative approach using semi-structured telephone interviews was undertaken with Australian oncologists who had referred patients to the telephone genetic counseling service. Sixteen oncologists participated and described referring patients to the telephone genetic counseling service due to the timeliness of obtaining a genetic counseling appointment and BRCA1/2 test results. They also reported this service offered convenience for patients living in regional or rural areas who then did not have to travel for an appointment with a clinical genetics service. Many oncologists noted the importance of in-person genetic counseling for patients who received positive BRCA1/2 results. Areas for improvement identified by the oncologists related to communication issues between the service and the patient. Overall, findings suggest that oncologists perceived telephone genetic counseling as an acceptable and useful healthcare service for patients with high-grade serous ovarian cancer. Moreover, they perceived telephone genetic counseling to be efficient, delivering convenient genetic counseling to patients.