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ObjectiveTo evaluate the association of Jewish cultural and religious identity and denominational affiliation with interest in, intention to undertake and uptake of population-based BRCA (Breast Cancer Gene)-testing.DesignCohort-study set within recruitment to GCaPPS-trial (ISRCTN73338115).SettingLondon Ashkenazi-Jewish (AJ) population.Population or sampleAJ men and women, >18 years.MethodsParticipants were self-referred, and attended recruitment clinics (clusters) for pre-test counselling. Subsequently consenting individuals underwent BRCA testing. Participants self-identified to one Jewish denomination: Conservative/Liberal/Reform/Traditional/Orthodox/Unaffiliated. Validated scales measured Jewish Cultural-Identity (JI) and Jewish Religious-identity (JR). Four-item Likert-scales analysed initial 'interest' and 'intention to test' pre-counselling. Item-Response-Theory and graded-response models, modelled responses to JI and JR scales. Ordered/multinomial logistic regression modelling evaluated association of JI-scale, JR-scale and Jewish Denominational affiliation on interest, intention and uptake of BRCA testing.Main outcome measuresInterest, intention, uptake of BRCA testing.ResultsIn all, 935 AJ women/men of mean age = 53.8 (S.D = 15.02) years, received pre-test education and counselling through 256 recruitment clinic clusters (median cluster size = 3). Denominational affiliations included Conservative/Masorti = 91 (10.2%); Liberal = 82 (9.2%), Reform = 135 (15.1%), Traditional = 212 (23.7%), Orthodox = 239 (26.7%); and Unaffiliated/Non-practising = 135 (15.1%). Overall BRCA testing uptake was 88%. Pre-counselling, 96% expressed interest and 60% intention to test. JI and JR scores were highest for Orthodox, followed by Conservative/Masorti, Traditional, Reform, Liberal and Unaffiliated Jewish denominations. Regression modelling showed no significant association between overall Jewish Cultural or Religious Identity with either interest, intention or uptake of BRCA testing. Interest, intention and uptake of BRCA testing was not significantly associated with denominational affiliation.ConclusionsJewish religious/cultural identity and denominational affiliation do not appear to influence interest, intention or uptake of population-based BRCA testing. BRCA testing was robust across all Jewish denominations.Tweetable abstractJewish cultural/religious factors do not affect BRCA testing, with robust uptake seen across all denominational affiliations.

OBJECTIVE: To determine risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) acceptability and effect of surgical prevention on menopausal sequelae/satisfaction/regret in women at increased ovarian cancer (OC) risk. DESIGN: Multicentre, cohort, questionnaire study (IRSCTN:12310993). SETTING: United Kingdom (UK). POPULATION: UK women without OC ≥18 years, at increased OC risk, with/without previous RRSO, ascertained through specialist familial cancer/genetic clinics and BRCA support groups. METHODS: Participants completed a 39-item questionnaire. Baseline characteristics were described using descriptive statistics. Logistic/linear regression models analysed the impact of variables on RRESDO acceptability and health outcomes. MAIN OUTCOMES: RRESDO acceptability, menopausal sequelae, satisfaction/regret. RESULTS: In all, 346 of 683 participants underwent risk-reducing salpingo-oophorectomy (RRSO). Of premenopausal women who had not undergone RRSO, 69.1% (181/262) found it acceptable to participate in a research study offering RRESDO. Premenopausal women concerned about sexual dysfunction were more likely to find RRESDO acceptable (odds ratio [OR] = 2.9, 95% CI 1.2-7.7, P = 0.025). Women experiencing sexual dysfunction after premenopausal RRSO were more likely to find RRESDO acceptable in retrospect (OR = 5.3, 95% CI 1.2-27.5, P

© 2019 Royal College of Obstetricians and Gynaecologists Objective: Unselected population-based BRCA testing provides the opportunity to apply genomics on a population-scale to maximise primary prevention for breast-and-ovarian cancer. We compare long-term outcomes of population-based and family-history (FH)/clinical-criteria-based BRCA testing on psychological health and quality of life. Design: Randomised controlled trial (RCT) (ISRCTN73338115) GCaPPS, with two-arms: (i) population-screening (PS); (ii) FH/clinical-criteria-based testing. Setting: North London Ashkenazi-Jewish (AJ) population. Population/Sample: AJ women/men. Methods: Population-based RCT (1:1). Participants were recruited through self-referral, following pre-test genetic counselling from the North London AJ population. Inclusion criteria: AJ women/men >18 years old; exclusion-criteria: prior BRCA testing or first-degree relatives of BRCA-carriers. Interventions: Genetic testing for three Jewish BRCA founder-mutations: 185delAG (c.68_69delAG), 5382insC (c.5266dupC) and 6174delT (c.5946delT), for (i) all participants in PS arm; (ii) those fulfilling FH/clinical criteria in FH arm. Linear mixed models and appropriate contrast tests were used to analyse the impact of BRCA testing on psychological and quality-of-life outcomes over 3 years. Main outcome measures: Validated questionnaires (HADS/MICRA/HAI/SF12) used to analyse psychological wellbeing/quality-of-life outcomes at baseline/1-year/2-year/3-year follow up. Results: In all, 1034 individuals (691 women, 343 men) were randomised to PS (n = 530) or FH (n = 504) arms. There was a statistically significant decrease in anxiety (P = 0.046) and total anxiety-&-depression scores (P = 0.0.012) in the PS arm compared with the FH arm over 3 years. No significant difference was observed between the FH and PS arms for depression, health-anxiety, distress, uncertainty, quality-of-life or experience scores associated with BRCA testing. Contrast tests showed a decrease in anxiety (P = 0.018), health-anxiety (P

The cost-effectiveness of population-based panel testing for high- and moderate-penetrance ovarian cancer (OC)/breast cancer (BC) gene mutations is unknown. We evaluate the cost-effectiveness of population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutation testing compared with clinical criteria/family history (FH) testing in unselected general population women. A decision-analytic model comparing lifetime costs and effects of criteria/FH-based BRCA1/BRCA2 testing is compared with BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing in those fulfilling clinical criteria/strong FH of cancer (≥10% BRCA1/BRCA2 probability) and all women age 30 years or older. Analyses are presented for UK and US populations. Identified carriers undergo risk-reducing salpingo-oophorectomy. BRCA1/BRCA2/PALB2 carriers can opt for magnetic resonance imaging/mammography, chemoprevention, or risk-reducing mastectomy. One-way and probabilistic sensitivity analysis (PSA) enabled model uncertainty evaluation. Outcomes include OC, BC, and additional heart disease deaths. Quality-adjusted life-years (QALYs), OC incidence, BC incidence, and incremental cost-effectiveness ratio (ICER) were calculated. The time horizon is lifetime and perspective is payer. Compared with clinical criteria/FH-based BRCA1/BRCA2 testing, clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is cost-effective (ICER = £7629.65/QALY or $49 282.19/QALY; 0.04 days' life-expectancy gained). Population-based testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutations is the most cost-effective strategy compared with current policy: ICER = £21 599.96/QALY or $54 769.78/QALY (9.34 or 7.57 days' life-expectancy gained). At £30 000/QALY and $100 000/QALY willingness-to-pay thresholds, population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 panel testing is the preferred strategy in 83.7% and 92.7% of PSA simulations; criteria/FH-based panel testing is preferred in 16.2% and 5.8% of simulations, respectively. Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing can prevent 1.86%/1.91% of BC and 3.2%/4.88% of OC in UK/US women: 657/655 OC cases and 2420/2386 BC cases prevented per million. Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than any clinical criteria/FH-based strategy. Clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than BRCA1/BRCA2 testing alone.

Ovarian cancer (OC) remains a lethal disease and a major cause of deaths from gynaecological cancer particularly in western countries. Despite advances in treatment, there have been only marginal improvements in survival rates over the last 30years. Additionally, the number of OC cases in the UK is estimated to increase by 27-45%, which translates to a 15% rise in the incidence rate by 2035.(1) A national OC screening programme is unavailable as this has not yet shown a conclusive mortality benefit.(2) Hence, primary prevention continues to be the cornerstone in reducing the burden of OC and improving health outcomes. This is essential to achieve long term transformational change and cost-efficiencies in our health-system. Its importance is amplified by current economic restraints, with a ~2.4% funding shortfall reported in the UK National-Health-Service (NHS). This article is protected by copyright. All rights reserved.

BACKGROUND: Population-based BRCA1/BRCA2 testing has been found to be cost-effective compared with family history-based testing in Ashkenazi-Jewish women were >30 years old with 4 Ashkenazi-Jewish grandparents. However, individuals may have 1, 2, or 3 Ashkenazi-Jewish grandparents, and cost-effectiveness data are lacking at these lower BRCA prevalence estimates. We present an updated cost-effectiveness analysis of population BRCA1/BRCA2 testing for women with 1, 2, and 3 Ashkenazi-Jewish grandparents. STUDY DESIGN: Decision analysis model. METHODS: Lifetime costs and effects of population and family history-based testing were compared with the use of a decision analysis model. 56% BRCA carriers are missed by family history criteria alone. Analyses were conducted for United Kingdom and United States populations. Model parameters were obtained from the Genetic Cancer Prediction through Population Screening trial and published literature. Model parameters and BRCA population prevalence for individuals with 3, 2, or 1 Ashkenazi-Jewish grandparent were adjusted for the relative frequency of BRCA mutations in the Ashkenazi-Jewish and general populations. Incremental cost-effectiveness ratios were calculated for all Ashkenazi-Jewish grandparent scenarios. Costs, along with outcomes, were discounted at 3.5%. The time horizon of the analysis is "life-time," and perspective is "payer." Probabilistic sensitivity analysis evaluated model uncertainty. RESULTS: Population testing for BRCA mutations is cost-saving in Ashkenazi-Jewish women with 2, 3, or 4 grandparents (22-33 days life-gained) in the United Kingdom and 1, 2, 3, or 4 grandparents (12-26 days life-gained) in the United States populations, respectively. It is also extremely cost-effective in women in the United Kingdom with just 1 Ashkenazi-Jewish grandparent with an incremental cost-effectiveness ratio of £863 per quality-adjusted life-years and 15 days life gained. Results show that population-testing remains cost-effective at the £20,000-30000 per quality-adjusted life-years and $100,000 per quality-adjusted life-years willingness-to-pay thresholds for all 4 Ashkenazi-Jewish grandparent scenarios, with ≥95% simulations found to be cost-effective on probabilistic sensitivity analysis. Population-testing remains cost-effective in the absence of reduction in breast cancer risk from oophorectomy and at lower risk-reducing mastectomy (13%) or risk-reducing salpingo-oophorectomy (20%) rates. CONCLUSION: Population testing for BRCA mutations with varying levels of Ashkenazi-Jewish ancestry is cost-effective in the United Kingdom and the United States. These results support population testing in Ashkenazi-Jewish women with 1-4 Ashkenazi-Jewish grandparent ancestry.

Associations between adolescent health-related quality of life (HRQoL), bullying, and aggression are not well understood. We used baseline data from a large-cluster randomized school trial to study the relationship between HRQoL, bullying experience, and other demographic factors. Cross-sectional self-reported questionnaires collected pre-randomization from the on-going INCLUSIVE trial. The questionnaires were completed in the classroom. The Gatehouse Bullying Scale measured bullying victimization and the Edinburgh Study of Youth Transitions and Crime school misbehavior subscale (ESYTC) measured aggressive behaviors. HRQoL was assessed using the Child Health Utility 9 Dimensions (CHU-9D) and general quality of life using the Pediatric Quality of Life Inventory (PedsQL). Participants were a cohort of year 7 students (age 11-12 years) from 40 state secondary schools in England. Descriptive statistics for the CHU-9D and PedsQL were calculated using standard methods with tests for differences in median scores by sex assessed using quantile regression. Correlation between HRQoL measures was conducted using Spearman's rank correlation coefficients. Predictors of HRQoL were identified using univariate and multiple regressions. A total of 6667 students filled out the questionnaire. The CHU-9D was correlated with the PedsQL (0.63, p

Ovarian cancer (OC) remains a lethal disease and a major cause of deaths from gynaecological cancer particularly in western countries. Despite advances in treatment, there have been only marginal improvements in survival rates over the last 30years. Additionally, the number of OC cases in the UK is estimated to increase by 27-45%, which translates to a 15% rise in the incidence rate by 2035.(1) A national OC screening programme is unavailable as this has not yet shown a conclusive mortality benefit.(2) Hence, primary prevention continues to be the cornerstone in reducing the burden of OC and improving health outcomes. This is essential to achieve long term transformational change and cost-efficiencies in our health-system. Its importance is amplified by current economic restraints, with a ~2.4% funding shortfall reported in the UK National-Health-Service (NHS). This article is protected by copyright. All rights reserved.

BACKGROUND: A new lower-cost rapid-throughput human papillomavirus (HPV) test (careHPV, Qiagen, Gaithersburg, USA) has been shown to have high sensitivity for the detection of high grade cervical intraepithelial neoplasia. METHODS: We assessed the outcomes and cost-effectiveness of careHPV screening in rural China, compared to visual inspection with acetic acid, when used alone (VIA) or in combination with Lugol's iodine (VIA/VILI). Using data on sexual behaviour, test accuracy, diagnostic practices and costs from studies performed in rural China, we estimated the cost-effectiveness ratio (CER) and associated lifetime outcomes for once-lifetime and twice-lifetime screening strategies, and for routine screening at 5-yearly, 10-yearly and IARC-recommended intervals. The optimal age range for once-lifetime screening was also assessed. RESULTS: For all strategies, the relative ordering of test technologies in reducing cervical cancer incidence and mortality was VIA (least effective); VIA/VILI; careHPV@1.0pg/ml and careHPV@0.5pg/ml (most effective). For once-lifetime strategies, maximum effectiveness was achieved if screening occurred between 35-50 years. Assuming a participation rate of ~70%, once-lifetime screening at age 35 years would reduce cancer mortality by 8% (for VIA) to 12% (for careHPV@0.5) over the long term, with a CER of US$557 (for VIA) to $959 (for careHPV@1.0) per life year saved (LYS) compared to no intervention; referenced to a 2008 GDP per capita in Shanxi Province of $2,975. Correspondingly, regular screening with an age-standardised participation rate of 62% (which has been shown to be achievable in this setting) would reduce cervical cancer mortality by 19-28% (for 10-yearly screening) to 43-54% (using IARC-recommended intervals), with corresponding CERs ranging from $665 (for 10-yearly VIA) to $2,269 (for IARC-recommended intervals using careHPV@1.0) per LYS. CONCLUSIONS: This modelled analysis suggests that primary careHPV screening compares favourably to visual inspection screening methodologies in rural China, particularly if used as part of a regular screening program

OBJECTIVES: The principal objective was to compare automation-assisted reading of cervical cytology with manual reading using the histological end point of cervical intraepithelial neoplasia grade II (CIN2) or worse (CIN2+). Secondary objectives included (i) an assessment of the slide ranking facility of the Becton Dickinson (BD) FocalPoint™ Slide Profiler (Becton Dickinson, Franklin Lakes, NJ, USA), especially 'No Further Review', (ii) a comparison of the two approved automated systems, the ThinPrep® Imaging System (Hologic, Bedford, MA, USA) and the BD FocalPoint Guided Screener Imaging System, and (iii) automated versus manual in terms of productivity and cost-effectiveness. DESIGN: A 1 : 2 randomised allocation of slides to either manual reading or automation-assisted paired with manual reading. Cytoscreeners were blinded to whether samples would be read only manually or manually paired with automated. Slide reading procedures followed real-life laboratory protocol to produce a final result and, for paired readings, the worse result determined the management. Costs per event were estimated and combined with productivity to produce a cost per slide, per woman and per CIN2+ and cervical intraepithelial neoplasia grade III (CIN3) or worse (CIN3+) lesion detected. Cost-effectiveness was estimated using cost per CIN2+ detected. Lifetime cost-effectiveness in terms of life-years and quality-adjusted life-years was estimated using a mathematical model. SETTING: Liquid-based cytology samples were obtained in primary care, and a small number of abnormal samples were obtained from local colposcopy clinics, from different women, in order to enrich the proportion of abnormals. All of the samples were read in a single large service laboratory. Liquid residues used for human papillomavirus (HPV) triage were tested (with Hybrid Capture 2, Qiagen, Crawley, UK) in a specialist virology laboratory in Edinburgh, UK. Histopathology was read by a specialist gynaecological pathology team blinded to HPV results and type of reading. PARTICIPANTS: Samples were obtained from women aged 25-64 years undergoing primary cervical screening in Greater Manchester, UK, with small proportions from women outside this age range and from women undergoing colposcopy. INTERVENTIONS: The principal intervention was automation-assisted reading of cervical cytology slides which was paired with a manual reading of the same slide. Low-grade cytological abnormalities (borderline and mild dyskaryosis) were triaged with HPV testing to direct colposcopy referral. Women with high-grade cytology were referred for colposcopy and those with negative cytology were returned to recall. MAIN OUTCOME MEASURES: The principal outcome measure was the sensitivity of automation-assisted reading relative to manual for the detection of CIN2+. A secondary outcome measure was cost-effectiveness of each type of reading to detect CIN2+. The study was powered to detect a relative sensitivity difference equivalent to an absolute difference of 5%. RESULTS: The principal finding was that automated reading was 8% less sensitive relative to manual, 6.3% in absolute terms. 'No further review' was very reliable and, if restricted to routine screening samples, < 1% of CIN2+ would have been missed. Automated and manual were very similar in terms of cost-effectiveness despite a 60%-80% increase in productivity for automation-assisted reading. CONCLUSIONS: The significantly reduced sensitivity of automated reading, combined with uncertainty over cost-effectiveness, suggests no justification at present to recommend its introduction. The reliability of 'no further review' warrants further consideration as a means of saving staff time. TRIAL REGISTRATION: Current Controlled Trials ISRCTN66377374. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 3. See the HTA programme website for further project information.