Genetic testing and personalized ovarian cancer screening: a survey of public attitudes

Background Advances in genetic technologies are expected to make population-wide genetic testing feasible. This could provide a basis for risk stratified cancer screening; but acceptability in the target populations has not been explored. Methods We assessed attitudes to risk-stratified ovarian cancer (OC) screening based on prior genetic risk assessment using a survey design. Home-based interviews were carried out by the UK Office of National Statistics in a population-based sample of 1095 women aged 18–74. Demographic and personal correlates of attitudes to risk-stratified OC screening based on prior genetic risk assessment were determined using univariate analyses and adjusted logistic regression models. Results Full data on the key analytic questions were available for 829 respondents (mean age 46 years; 27 % ‘university educated’; 93 % ‘White’). Relatively few respondents felt they were at ‘higher’ or ‘much higher’ risk of OC than other women of their age group (7.4 %, n = 61). Most women (85 %) said they would ‘probably’ or ‘definitely’ take up OC genetic testing; which increased to 88 % if the test also informed about breast cancer risk. Almost all women (92 %) thought they would ‘probably’ or ‘definitely’ participate in risk-stratified OC screening. In multivariate logistic regression models, university level education was associated with lower anticipated uptake of genetic testing (p = 0.009), but with more positive attitudes toward risk-stratified screening (p <0.001). Perceived risk was not significantly associated with any of the outcome variables. Conclusions These findings give confidence in taking forward research on integration of novel genomic technologies into mainstream healthcare

Attitudes towards a programme of risk assessment and stratified management for ovarian cancer: a focus group study of UK South Asians' perspectives

A crucial first step to enable implementation of population-based genetic risk assessment and management in OC is to raise awareness of OC within SA communities. It will be important to engage with the SA community early on in programme implementation to address their specific concerns and to ensure culturally tailored decision support. Population-based risk assessment, using genetic testing and the provision of appropriate risk management, could lead to prevention, early detection and improved clinical management of ovarian cancer (OC). Previous research with mostly white British participants found positive attitudes towards such a programme. The current study aimed to explore the attitudes of South Asian (SA) women and men in the UK with the aim of identifying how best to implement such a programme to minimise distress and maximise uptake. Semistructured qualitative focus group discussions. Community centres across North London and Luton. 49 women and 13 men who identified as SA (Indian, Pakistani or Bangladeshi), which constitutes the largest non-European ethnic minority group in the UK. Seven community-based focus groups were held. Group discussions were transcribed verbatim, coded and analysed thematically. Awareness and knowledge of OC symptoms and specific risk factors was low. The programme was acceptable to most participants and attitudes to it were generally positive. Participants' main concerns related to receiving a high-risk result following the genetic test. Younger women may be more cautious of genetic testing, screening or risk-reducing surgery due to the importance of marriage and childbearing in their SA cultures. CONCLUSIONS OBJECTIVE DESIGN SETTING PARTICIPANTS METHODS RESULT

Impact of weather cues and resource dynamics on mast occurrence in the main forest tree species in Europe

Mast seeding, the synchronised occurrence of large amounts of fruits and seeds at irregular intervals, is a reproductive strategy in many wind-pollinated species. Although a series of studies have investigated mast year (MY) patterns in European forest tree species at the regional scale, there are few recent evaluations at a European scale on the impact of weather variables (weather cues) and resource dynamics on mast behaviour. Thus the main objective of this study is to investigate the impact of specific weather conditions, as environmental drivers for MYs, on resources in Fagus sylvatica L., Quercus petraea (Matt.)Liebl., Quercus robur L., Picea abies (L.) Karst. and Pinus sylvestris L. at a European level and to explore the robustness of the relationships in smaller regions within Europe. Data on seed production originating from the International Co-operative Programme on Assessment and Monitoring of Air Pollution Effects on Forests (ICP Forests) were analysed. Three beta regression models were applied to investigate the impact of seasonal weather variables on MY occurrence, as well as the influence of fruiting intensity levels in the years prior to MYs. Resource dynamics are analysed at three different spatial scales (continent, countries and ecoregions). At a European scale, important weather cues for beech MYs were a cold and wet summer two years before a MY, a dry and warm summer one year before a MY and a warm spring in the MY. For spruce, a cold and dry summer two years prior to a MY and a warm and dry summer in the year before the MY showed the strongest associations with the MY. For oak, high spring temperature in the MY was the most important weather cue. For beech and spruce, and to some extent also for oak species, the best fitting models at European scale were well reflected by those found at smaller scales. For pine, best fitting models were highly diverse concerning weather cues. Fruiting levels were high in all species two years before the MY and also high one year before the MY in the oak species and in pine. In beech, fruiting levels one year before the MY were not important and in spruce, they were inconsistent depending on the region. As a consequence, evidence of resource depletion could only be seen in some regions for spruce.publishedVersio

Population Testing for Cancer Predisposing BRCA1/BRCA2 Mutations in the Ashkenazi-Jewish Community: A Randomized Controlled Trial

Technological advances raise the possibility of systematic population-based genetic testing for cancer-predisposing mutations, but it is uncertain whether benefits outweigh disadvantages. We directly compared the psychological/quality-of-life consequences of such an approach to family history (FH)-based testing

Annual outpatient hysteroscopy and endometrial sampling (OHES) in HNPCC/Lynch syndrome (LS)

Background: LS women have a 40-60 % lifetime risk of endometrial cancer (EC). Most international guidelines recommend screening. However, data on efficacy are limited. Purpose: To assess the performance of OHES for EC screening in LS and compare it with transvaginal ultrasound (TVS) alone. Methods: A prospective observational cohort study of LS women attending a tertiary high-risk familial gynaecological cancer clinic was conducted. LS women opting for EC screening underwent annual OHES and TVS. Histopathological specimens were processed using a strict protocol. Data of women screened between October 2007 and March 2010 were analysed from a bespoke database. Histology was used as the gold standard. Diagnostic accuracy of OHES was compared with TVS using specificity, and positive (PLR) and negative (NLR) likelihood ratios. Results: Forty-one LS women underwent 69 screens (41 prevalent, 28 incident). Four (three prevalent, one incident) women were detected to have EC/atypical endometrial hyperplasia (AEH), five had endometrial polyps and two had endometrial hyperplasia (EH) on OHES. TVS detected two of four EC/AEH. OHES had similar specificity of 89.8 % (CI 79.2, 96.2 %), but higher PLR 9.8 (CI 4.6, 21) and lower NLR (zero) compared to TVS: specificity 84.75 %(CI 73, 92.8 %), PLR 3.28 (CI 1.04, 10.35) and NLR 0.59 (CI 0.22, 1.58). No interval cancers occurred over a median follow-up of 22 months. The annual incidence was 3.57 % (CI 0.09, 18.35) for EC, 10.71 % (CI 2.27, 28.23) for polyps and 21.4 % (CI 8.3, 40.1) for any endometrial pathology. Conclusions: Our findings suggest that in LS, annual OHES is acceptable and has high diagnostic accuracy for EC/AEH screening. Larger international studies are needed for confirmation, given the relatively small numbers of LS women at individual centres. It reinforces the current recommendation that endometrial sampling is crucial when screening these women. © 2012 Springer-Verlag

Cost-effectiveness of Population Screening for BRCA Mutations in Ashkenazi Jewish Women Compared With Family History-Based Testing

BACKGROUND: Population-based testing for BRCA1/2 mutations detects the high proportion of carriers not identified by cancer family history (FH)-based testing. We compared the cost-effectiveness of population-based BRCA testing with the standard FH-based approach in Ashkenazi Jewish (AJ) women. METHODS: A decision-analytic model was developed to compare lifetime costs and effects amongst AJ women in the UK of BRCA founder-mutation testing amongst: 1) all women in the population age 30 years or older and 2) just those with a strong FH (≥10% mutation risk). The model assumes that BRCA carriers are offered risk-reducing salpingo-oophorectomy and annual MRI/mammography screening or risk-reducing mastectomy. Model probabilities utilize the Genetic Cancer Prediction through Population Screening trial/published literature to estimate total costs, effects in terms of quality-adjusted life-years (QALYs), cancer incidence, incremental cost-effectiveness ratio (ICER), and population impact. Costs are reported at 2010 prices. Costs/outcomes were discounted at 3.5%. We used deterministic/probabilistic sensitivity analysis (PSA) to evaluate model uncertainty. RESULTS: Compared with FH-based testing, population-screening saved 0.090 more life-years and 0.101 more QALYs resulting in 33 days' gain in life expectancy. Population screening was found to be cost saving with a baseline-discounted ICER of -£2079/QALY. Population-based screening lowered ovarian and breast cancer incidence by 0.34% and 0.62%. Assuming 71% testing uptake, this leads to 276 fewer ovarian and 508 fewer breast cancer cases. Overall, reduction in treatment costs led to a discounted cost savings of £3.7 million. Deterministic sensitivity analysis and 94% of simulations on PSA (threshold £20000) indicated that population screening is cost-effective, compared with current NHS policy. CONCLUSION: Population-based screening for BRCA mutations is highly cost-effective compared with an FH-based approach in AJ women age 30 years and older

Impact of a decision aid about stratified ovarian cancer risk-management on women's knowledge and intentions: a randomised online experimental survey study.

BACKGROUND: Risk stratification using genetic and other types of personal information could improve current best available approaches to ovarian cancer risk reduction, improving identification of women at increased risk of ovarian cancer and reducing unnecessary interventions for women at lower risk. Amounts of information given to women may influence key informed decision-related outcomes, e.g. knowledge. The primary aim of this study was to compare informed decision-related outcomes between women given one of two versions (gist vs. extended) of a decision aid about stratified ovarian cancer risk-management. METHODS: This was an experimental survey study comparing the effects of brief (gist) information with lengthier, more detailed (extended) information on cognitions relevant to informed decision-making about participating in risk-stratified ovarian cancer screening. Women with no personal history of ovarian cancer were recruited through an online survey company and randomised to view the gist (n = 512) or extended (n = 519) version of a website-based decision aid and completed an online survey. Primary outcomes were knowledge and intentions. Secondary outcomes included attitudes (values) and decisional conflict. RESULTS: There were no significant differences between the gist and extended conditions in knowledge about ovarian cancer (time*group interaction: F = 0.20, p = 0.66) or intention to participate in ovarian cancer screening based on genetic risk assessment (t(1029) = 0.43, p = 0.67). There were also no between-groups differences in secondary outcomes. In the sample overall (n = 1031), knowledge about ovarian cancer increased from before to after exposure to the decision aid (from 5.71 to 6.77 out of a possible 10: t = 19.04, p < 0.001), and 74% of participants said that they would participate in ovarian cancer screening based on genetic risk assessment. CONCLUSIONS: No differences in knowledge or intentions were found between women who viewed the gist version and women who viewed the extended version of a decision aid about risk-stratified ovarian cancer screening. Knowledge increased for women in both decision aid groups. Further research is needed to determine the ideal volume and type of content for decision aids about stratified ovarian cancer risk-management. TRIAL REGISTRATIONS: This study was registered with the ISRCTN registry; registration number: ISRCTN48627877 .This work was funded by Cancer Research UK (Grant Code: C1005/A12677) and The Eve Appeal Gynaecological Cancer Charity

Population-based genetic risk prediction and stratification for ovarian cancer: views from women at high risk

There is an opportunity to improve outcomes for ovarian cancer (OC) through advances in risk stratification, early detection and diagnosis. A population-based OC genetic risk prediction and stratification program is being developed. A previous focus group study with individuals from the general population showed support for the proposed program. This qualitative interview study explores the attitudes of women at high risk of OC. Eight women participated in one-on-one, in-depth, semi-structured interviews to explore: experiences of learning of OC risk, risk perceptions, OC knowledge and awareness, and opinions on risk stratification approach. There was evidence of strong support for the proposed program. Benefits were seen as providing reassurance to women at low risk, and reducing worry in women at high risk through appropriate clinical management. Stratification into ‘low’ and ‘high’ risk groups was well-received. Participants were more hesitant about stratification to the ‘intermediate’ risk group. The data suggest formats to effectively communicate OC risk estimates will require careful thought. Interactions with GPs were highlighted as a barrier to OC risk assessment and diagnosis. These results are encouraging for the possible introduction and uptake of a risk prediction and stratification program for OC in the general population

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries