Unselected population-based personalised ovarian cancer (OC) risk assessment combining genetic/epidemiology/hormonal data has not previously been undertaken. We aimed to perform a feasibility study of OC risk stratification of general population women using a personalised OC risk tool followed by risk management. Volunteers were recruited through London primary care networks. Inclusion criteria: women ≥18 years. Exclusion criteria: prior ovarian/tubal/peritoneal cancer, previous genetic testing for OC genes. Participants accessed an online/web-based decision aid along with optional telephone helpline use. Consenting individuals completed risk assessment and underwent genetic testing (BRCA1/BRCA2/RAD51C/RAD51D/BRIP1, OC susceptibility single-nucleotide polymorphisms). A validated OC risk prediction algorithm provided a personalised OC risk estimate using genetic/lifestyle/hormonal OC risk factors. Population genetic testing (PGT)/OC risk stratification uptake/acceptability, satisfaction, decision aid/telephone helpline use, psychological health and quality of life were assessed using validated/customised questionnaires over six months. Linear-mixed models/contrast tests analysed impact on study outcomes. Main outcomes: feasibility/acceptability, uptake, decision aid/telephone helpline use, satisfaction/regret, and impact on psychological health/quality of life. In total, 123 volunteers (mean age = 48.5 (SD = 15.4) years) used the decision aid, 105 (85%) consented. None fulfilled NHS genetic testing clinical criteria. OC risk stratification revealed 1/103 at ≥10% (high), 0/103 at ≥5%–<10% (intermediate), and 100/103 at <5% (low) lifetime OC risk. Decision aid satisfaction was 92.2%. The telephone helpline use rate was 13% and the questionnaire response rate at six months was 75%. Contrast tests indicated that overall depression (p = 0.30), anxiety (p = 0.10), quality-of-life (p = 0.99), and distress (p = 0.25) levels did not jointly change, while OC worry (p = 0.021) and general cancer risk perception (p = 0.015) decreased over six months. In total, 85.5–98.7% were satisfied with their decision. Findings suggest population-based personalised OC risk stratification is feasible and acceptable, has high satisfaction, reduces cancer worry/risk perception, and does not negatively impact psychological health/quality of life.

Unselected population-based personalised ovarian cancer (OC) risk assessments combining genetic, epidemiological and hormonal data have not previously been undertaken. We aimed to understand the attitudes, experiences and impact on the emotional well-being of women from the general population who underwent unselected population genetic testing (PGT) for personalised OC risk prediction and who received low-risk (<5% lifetime risk) results. This qualitative study was set within recruitment to a pilot PGT study using an OC risk tool and telephone helpline. OC-unaffected women ≥ 18 years and with no prior OC gene testing were ascertained through primary care in London. In-depth, semi-structured and 1:1 interviews were conducted until informational saturation was reached following nine interviews. Six interconnected themes emerged: health beliefs; decision making; factors influencing acceptability; effect on well-being; results communication; satisfaction. Satisfaction with testing was high and none expressed regret. All felt the telephone helpline was helpful and should remain optional. Delivery of low-risk results reduced anxiety. However, care must be taken to emphasise that low risk does not equal no risk. The main facilitators were ease of testing, learning about children’s risk and a desire to prevent disease. Barriers included change in family dynamics, insurance, stigmatisation and personality traits associated with stress/worry. PGT for personalised OC risk prediction in women in the general population had high acceptability/satisfaction and reduced anxiety in low-risk individuals. Facilitators/barriers observed were similar to those reported with genetic testing from high-risk cancer clinics and unselected PGT in the Jewish population.

Introduction: A novel referral pathway for exhibited breast symptom (EBS) referrals to manage increasing referrals of urgent suspected cancer (USC) was implemented in our trust. We report on the safety and effect on compliance with the 2-week-wait rule (2WW). Methods: A single-centre longitudinal observational study included all patients referred to a UK breast unit during 13 May 2019 to 27 March 2020 (period 1) and 8 February 2021 to 31 January 2022 (period 2). USC referrals were assessed in a one-stop clinic (red flag clinic [RFC]); EBS referrals were assessed in a new clinic in which clinical evaluation was performed and imaging occurred subsequently (blue flag clinic [BFC]). Patients were followed up to determine the symptomatic interval cancer rate. Results: There were 9,695 referrals; 1,655 referrals (17%) were assessed in the BFC after 63 exclusions. Some 95.9% of patients had a benign clinical examination (P1/P2), 80.1% had imaging (mammogram or ultrasound) and 4% had a tissue biopsy. In total, 16/1,655 (0.97%) BFC patients and 510/7,977 (8.2%) RFC patients were diagnosed with breast cancer (breast cancer detection rate). Some 1,631 patients (with 1,639 referrals) were discharged and followed up for a median of 17 months (interquartile range 12–32) with one subsequent cancer diagnosis (symptomatic interval cancer rate, 0.06%). Implementation of the BFC pathway increased 3-month average trust performance of USC referrals with 2WW standard from 8.5% to 98.7% (period 1) and from 30% to 66% (period 2). Conclusions: The BFC pathway for EBS patients is safe and implementation led to improvement against the 2WW target for USC referrals, ensuring resources are prioritised to patients with the highest likelihood of breast cancer.

Background and objectives: Implantable cardioverter defibrillator (ICD) therapy is indicated following a myocardial infarction (MI) to curtail the risk of sudden cardiac death (SCD) in patients who are classified as high-risk, defined by a left ventricular ejection fraction (LVEF) ≤35%. The understanding of risk in patients with ischaemic injury who do not meet these criteria is limited. This study aims to assess the burden of SCD in patients’ post-MI with LVEF 36–50%. Methods: Articles reporting mortality and SCD outcomes for participants with LVEF 36–50% post-MI without additional risk stratification or intervention were included. Medline, Embase and Cochrane databases were searched from index entries until the present. Data were synthesised using a random-effects model. Competing risk adjusted number needed to treat (NNT) for ICD implantation was calculated. This study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: 7435 records were identified, five studies with 9345 patients were included. The pooled annual rate of SCD in patients with LVEF 36–50% post-MI was 1.74% (95% CI 1.02 to 2.95); a higher annual rate of 6.34% was observed for LVEF≤35% (p=0.03) while a lower yearly rate of 0.55% was observed for LVEF >50% (p=0.02). The proportion of mortality due to SCD was similar across all LVEF strata (p=0.79). Very high between-study heterogeneity was observed (I ² =89.9% for SCD and I ² =96.8% for all-cause mortality). During exploratory modelling, the primary prevention ICD NNT for patients with LVEF 36–50% was 19 when applying the MADIT-II ICD treatment effect (HR 0.33, 95% CI 0.20 to 0.53) and extrapolation to a 5-year device lifespan. Conclusion: This is the first meta-analysis reviewing post-MI patients with LVEF 36–50%. These findings highlight a clinically relevant unmet need for patients who carry a substantial burden of SCD despite being outside current ICD eligibility criteria. Further study is needed to improve risk stratification within this population and determine whether suitable intervention is beneficial. PROSPERO registration number: CRD42024551830.