Background:Young people's mental health worsened during and since the coronavirus disease discovered in 2019 pandemic. School environments play a key role in young people's mental health. Learning Together for Mental Health is a whole-school intervention aiming to promote mental health in secondary schools, adapted from the previous Learning Together intervention which was found effective in reducing bullying and promoting mental health. Objective:To adapt Learning Together to increase focus on mental health so producing the Learning Together for Mental Health intervention and evaluate the appropriateness of conducting a Phase III trial of the Learning Together for Mental Health intervention regarding pre-defined progression criteria relating to the intervention and trial methods, and assessing intervention feasibility, reach and acceptability, feasibility of trial measures and procedures, potential mechanisms and possible harms. Design and methods:We conducted a feasibility study with baseline and follow-up surveys, process evaluation and economic-evaluation feasibility-testing. Setting and participants:One school participated in intervention adaptation. Our feasibility study included four state, mixed-sex secondary schools in southern England (one of which dropped out after baselines and was replaced with another). We recruited 640 year-7 (age 11-12) students at baseline survey and 566 year-10 (age 14-15) students at 12-month follow-up. Baseline and follow-up participants were different groups, as the focus was assessing feasibility for the age groups to be surveyed at baseline and follow-up in a Phase III randomised controlled trial. Twenty staff, 27 year-8 (age 12-13) students and 22 year-10 students participated in qualitative research as did two trainers and one external facilitator. Interventions:As part of our feasibility study, all schools received the Learning Together for Mental Health intervention for one academic school year. Main outcome measures:Pre-defined criteria for progression to a Phase III trial. Results:The intervention was successfully adapted from the previous intervention using public involvement. The trial met all criteria for progression to Phase III. The all-staff and in-depth restorative practice training were implemented with fidelity in all schools and all schools had at least two staff trained in-depth in restorative practice. Curriculum training was delivered with fidelity in three of four schools. The response rate to the baseline (needs) survey across the three participating schools was 79%. Progression required at least two schools to have delivered the curriculum with at least 50% fidelity, which was achieved; one of the two schools which delivered the curriculum reported over 80% fidelity and the other school reported over 75% fidelity. All students and staff across all four schools who completed the action group survey and 93% of senior leadership team members who completed the senior leadership team survey reported that Learning Together for mental health was a good way to promote student Mental Health. Potential mechanisms of action involve promoting student sense of school belonging and practical reasoning and skills. No harms were reported. Trial measures and procedures were feasible and acceptable to implement. Intervention and trial refinement are suggested. Limitations:Our study involved a small, purposive sample of schools and students which are not representative of those in England. Conclusions:With some minor amendments, Learning Together for Mental Health should be subject to a future Phase III trial of effectiveness. Future work:The intervention should be refined by making the curriculum optional and improving materials. Funding:This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme as award number NIHR131594.

In the North Thames Mainstreaming of Breast Cancer Genetic Testing (NT-MBGT) programme, we piloted testing for breast cancer susceptibility genes (BCSGs) in unselected breast cancer (BC) patients, deploying a clinician-light ‘BRCA-DIRECT’ mainstreaming pathway; this included home saliva-testing and consent with postal return, written and digital materials, with full access to a Genetic Counsellor Telephone helpline. Across 14 National Health Service (NHS) breast oncology units, we successfully tested 3515 newly-diagnosed BC patients with high levels of patient and breast healthcare professional (HCP) satisfaction and genetics HCPs reporting decreases in service referrals. The pick-up rate of gPVs was 4.7% (166 germline Pathogenic Variants (gPVs) across seven BCSGs). Examining application of current NHS eligibility criteria to the unselected cohort, testing would have been offered to 20.6% of patients with identification of 49.2% of gPVs in high penetrance (HP)-BCSGs (BRCA1/BRCA2/PALB2) and 18.2% of gPVs in intermediate penetrance-BCSGs (CHEK2/ATM/RAD51C/RAD51D). Designing ‘Ultra-simple’ eligibility criteria suitable for mainstreaming, detection (sensitivity) could be improved to 81.1% and 70.4% respectively, whilst increasing testing to 49.7% of BC cases. Evidence from the NT-MBGT programme demonstrates that expanding BCSG-testing via a clinician-light pathway is acceptable and feasible, without increasing the burden on limited breast and genetics workforce, and has high satisfaction.

BACKGROUND:Risk-reducing hysterectomy (RRH) is the most effective endometrial cancer preventive strategy. Understanding health-related quality-of-life using health-related utility-scores (HRUS) is essential for counselling, shared decision-making, and informing health-economic evaluations of endometrial cancer prevention. This study aimed to determine HRUS for premenopausal RRH, with and without bilateral salpingo-oophorectomy (BSO). METHODS:Preventing Endometrial-Cancers: Comparing Risk-Reducing Strategies (PRESCORES) (ISRCTN17432105) part-2 is a UK-based randomised vignette study. Following a robust development process, vignettes described four postoperative health-states for a 40-year-old otherwise-healthy woman: "RRH at 1-month", "RRH at 1-year", "RRH-BSO at 1-month", "RRH-BSO at 1-year". These were valued using EQ-5D by participants recruited from the UK general-population and HRUS calculated. Utilities were subsequently adjusted by age-and sex-matched general-population reference values. Association of variables was explored with ordinary-least-squares regression with non-parametric bootstrapping. FINDINGS:Overall, 1001 women were included and randomised to 1-of-4 groups. The mean-age(±SD) was 53.6 (±11.4) years. Mean(±SD) HRUS were 0.942 (±0.072) for "RRH at 1-year", 0.841 (±0.137) for "RRH-BSO at 1-year", 0.670 (±0.149) for "RRH at 1-month", and 0.733 (±0.190) for "RRH-BSO at 1-month", with significant difference between each group (p < 0.001). Adjusting for age-sex-matched population reference utilities, HRUS were 1.000(95% CI:1.00-1.00), 0.994(95% CI:0.97-1.00), 0.866(95% CI:0.84-0.90) and 0.791(95% CI:0.77-0.81), respectively. Participant factors associated with vignette valuations included age, obesity, heavy menstrual-bleeding, higher income and mixed/other ethnicity. CONCLUSION:This randomised study provides HRUS following premenopausal RRH with and without BSO at two postoperative time-points, with adjustment against the age-and sex-matched general reference-population. These values are of relevance for informing counselling of women at increased endometrial cancer-risk regarding RRH and for health-economic evaluations.

Background:Understanding the impact of risk-reducing hysterectomy (RRH) on health-related quality-of-life is essential for informed decision-making around endometrial cancer prevention and has not been previously investigated. This study aimed to estimate health-related utilities in women who received RRH. Methods:PRESCORES was a multicentre cross-sectional study (ISRCTN17432105). We invited 4031 UK women ≥18 years with confirmed Lynch Syndrome, without prior gynaecological cancer, to participate between May 2023 and November 2024. The main outcome was a complete-case adjusted mean-difference in EQ-5D utility scores between participants who had undergone RRH or not, and by pre/post-menopausal age groups. Quality-of-life was measured at the time of survey completion, and retrospectively 4 months after surgery in the RRH-group. The Cancer-Worry Scale instrument was also evaluated by RRH group. Sensitivity analysis considered alternative statistical methods, multiple imputation, and restricting analysis to people 35-80 years. Findings:Analysis included 1120 participants: 529 had undergone RRH with a median age of 55 years (IQR 48-62), compared with 39 years (33-52) without RRH. The RRH-group was significantly more likely to have had cancer, physical co-morbidities, be parous and used aspirin. Adjusted mean utilities were slightly lower in the RRH than no-RRH group (difference -0.020, 95% CI -0.045 to 0.004; p = 0.11), much lower for premenopausal women (-0.041, -0.074 to -0.008), but similar for postmenopausal women (0.003, -0.036 to 0.042). Cancer-Worry-Scale scores were lower in the RRH group (mean-difference 0.48, 95% CI -0.807 to -0.157; p = 0.0037). Interpretation was robust to sensitivity analyses. Interpretation:Health-related quality-of-life in women with Lynch Syndrome is likely to be lower following RRH in younger, pre-menopausal women. This is relevant for counselling, RRH decision making, and economic evaluations of women with Lynch Syndrome, with increased endometrial cancer risk. Funding:Rosetrees Trust (CF1\100001) and Barts Charity (G-002286 and MRC0167).

Importance:Risk-reducing early-salpingectomy (RRES) and delayed oophorectomy (DO) is a novel 2-stage alternative prevention strategy to risk-reducing salpingo-oophorectomy (RRSO) that avoids detrimental consequences of premature menopause. However, direct data on the clinical effectiveness for ovarian cancer (OC) risk reduction are lacking. Objective:To explore how to define clinical effectiveness from prospective cohort studies using the estimand framework and sample size requirements. Design, Setting, and Participants:In this comparative effectiveness research study, estimand and analysis options were considered to evaluate the clinical effectiveness of RRES with DO by extending the UK PROTECTOR cohort study, a multicenter, prospective, observational, national cohort study (N = 1250 recruited from January 1, 2019, to December 31, 2024) evaluating RRES and DO for OC surgical prevention. Participants were premenopausal women 30 years or older at increased OC risk due to BRCA1/BRCA2 pathogenic variants. Participants could choose RRES, RRSO, or no surgery at entry. Sample size requirements used initial data (eg, age and BRCA1/2 distribution) from PROTECTOR (analysis undertaken from January 1, 2024, to December 31, 2025). Main Outcomes and Measures:Incidence of OC after (not at) RRES and before or at DO in women with normal histologic analysis findings at surgery. The proportion of cancers prevented was estimated as the completement of the observed (O) to expected (E; assuming no preventive effect of surgery) number of cancers detected (1 - O/E). Results:Initial data were obtained from 889 women in PROTECTOR (overall mean [SD] age, 39 [5] years), with 255 (28.7%) choosing RRSO (mean [SD] age, 42 [4] years), 405 (45.5%) choosing RRES (mean [SD] age, 38 [4] years), and 229 (25.7%) choosing no surgery (mean [SD], 38 [5] years). The preferred estimand outcome was OC incidence after surgery (RRES or RRSO) with a "while on intervention" strategy to account for intercurrent events. The primary target measure was the proportion of cancers prevented for RRES vs no surgery with superiority testing. The secondary target measure was noninferiority of RRES vs RRSO. An estimated 1150 RRES participants with 8 to 10 years of follow-up would provide approximately 92% power to show that 20% or more of cancers are prevented using a 1-sample binomial test of the O:E risk (external reference) at the 5% level under a range of assumptions and at least the same power for a noninferiority margin for the proportion of cancers prevented by RRES of those prevented by RRSO. Estimands based on incidence ratios had an infeasible sample size. Conclusions and Relevance:In this comparative effectiveness study of UK BRCA carriers, the estimand differed from other ongoing clinical effectiveness studies of RRES and DO. Advantages include direct use of expected risk at baseline (unknown at design stage), easier interpretation across cohorts than absolute risk differences, and providing a feasible recruitment target for PROTECTOR to evaluate clinical effectiveness.

Importance:Expanding access to genetic testing and availability of validated breast cancer (BC) risk prediction models are increasingly identifying women at elevated BC risk who do not carry high-penetrance BRCA1/BRCA2/PALB2 pathogenic variants. The precise BC risk threshold for offering risk-reducing mastectomy (RRM) for BC prevention is unknown. Objective:To define the lifetime BC risk thresholds for RRM to be cost-effective compared with nonsurgical alternatives for BC prevention. Design, Setting, and Participants:This economic evaluation used a decision-analytic Markov model to compare the cost-effectiveness of RRM with BC screening and medical prevention in a simulated cohort. Extensive sensitivity analyses were performed. The study setting was from a UK payer perspective over a lifetime horizon until age 80 years. The simulated cohort included women aged 30 to 60 years at varying lifetime BC risks from 17% to 50%. The study was conducted between September 2022 and September 2024. Exposures:Undergoing RRM or receiving risk-stratified BC screening with medical prevention (tamoxifen or anastrozole). Main Outcomes and Measures:The incremental cost-effectiveness ratio was calculated as incremental cost per quality-adjusted life-year (QALY) gained and compared with the UK willingness-to-pay (WTP) threshold of £20 000 (US $27 037) to £30 000 (US $40 555) per QALY. BC cases prevented were estimated at the population level. Results:In the simulated cohort of 100 000 thirty-year-old women in the UK, undergoing RRM became cost-effective at a 34% lifetime BC risk using the £30 000 (US $40 555) per QALY WTP threshold. This increased to a 42% lifetime BC risk using the £20 000 (US $27 037) per QALY WTP threshold. The identified lifetime BC risk thresholds for RRM to be cost-effective among women aged 35, 40, 45, 50, 55, and 60 years were 31%, 29%, 29%, 32%, 36%, and 42%, respectively, using the £30 000 (US $40 555) per QALY WTP threshold. Overall, undergoing RRM was deemed cost-effective for women aged 30 to 55 years with a lifetime BC risk of at least 35%, with more than 50% of simulations being cost-effective in probabilistic sensitivity analysis. Offering RRM for women with a lifetime BC risk of 35% or higher could potentially prevent approximately 6538 (95% CI, 4454-7041), or approximately 11% (95% CI, 8%-12%), of the 58 756 BC cases occurring annually in women in the UK. In the probabilistic sensitivity analysis, 20.71% to 59.96%, 44.04% to 81.29%, and 97.26% to 99.35% of simulations were cost-effective for women with 35%, 40%, and 50% lifetime BC-risk undergoing RRM at age 30 under the £20 000 to £30 000 per QALY WTP threshold, respectively. Conclusions and Relevance:In this economic evaluation, undergoing RRM appears cost-effective for women aged 30 to 55 years with a lifetime BC risk of 35% or higher. These results could have significant clinical implications to expand access to RRM beyond BRCA1/BRCA2/PALB2 pathogenic variant carriers. Future studies evaluating the acceptability, uptake, and long-term outcomes of RRM among these women are warranted.

Background:Despite high rates of adolescent mental health problems, there are few effective school-based interventions to address this. Whole-school interventions offer a feasible and sustainable means of promoting mental health, but to date, few have been evaluated. Previously we trialled the Learning Together intervention comprising local needs assessment, student and staff participation in decision-making, restorative practice, and a social and emotional skills curriculum. This was effective not only in preventing bullying (primary outcome) but also in promoting mental well-being and psychological functioning (secondary outcomes). We adapted Learning Together to develop Learning Together for Mental Health, focused on promoting mental health. Objective:This paper reports on quantitative data on intervention implementation fidelity, reach and acceptability to assess progression to a Phase III trial. Design:We drew on student baseline and follow-up surveys and an integral process evaluation from a non-randomised feasibility study involving four secondary schools. Setting:Southern England. Participants:Students in year 8 (age 12/13) at baseline and year 10 (age 14/15) at follow-up and school staff and students and intervention trainers and facilitators completing process evaluation tools. Interventions:Whole-school intervention featuring student needs assessment, action groups involving staff and students which selected actions from an evidence-based menu, restorative practice to improve relationships and address student behaviour and a social and emotional skills curriculum. Results:Restorative practice training was implemented with fidelity in all schools. Curriculum training was implemented with fidelity in three of four schools. The response rate to the needs survey across the three schools that participated was 79%. Action groups were implemented with fidelity. Action groups at all four schools completed at least one locally decided action and chose at least one action from the menu of evidence-based options. Restorative practice was implemented across all schools. Of lessons that were observed and lessons for which teachers returned logbooks, curriculum delivery was implemented with fidelity. However, two schools delivered 50% or less of the recommended lessons, and not all teachers completed logbooks. All students and staff completing surveys reported finding the Learning Together for Mental Health intervention a good way to promote student mental health. Over a third of students reported definite awareness of actions being undertaken by their schools to improve student mental health. All pre-defined progression criteria to proceed to a Phase III trial were met. The intervention was delivered with good fidelity and had strong acceptability. Limitations:The schools involved may not be representative of those which we would recruit to a Phase III trial. Conclusions:The study met all pre-determined progression criteria, and the intervention is ready for a Phase III trial with minor adaptations. Future work:A Phase III trial of effectiveness is justified. Funding:This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme as award number NIHR131594.

Background: In 2022, there were approximately 19.96 million new cancer cases globally according to GLOBOCAN, with breast cancer emerging as the most commonly diagnosed female cancer. In China, there were 0.36 million new cases and 75,000 deaths due to breast cancer of women in 2022. However, studies focusing on the cost of treatment and the economic burden of female breast cancer patients in China were conducted within specific provinces, cities, or hospitals, and there lacks a comprehensive analysis of total treatment cost. This study aimed to analyze the costs associated with female breast cancer patients in China using data from the China Health Insurance Research Association (CHIRA) and to explore the factors influencing costs. Methods: Female breast cancer patients aged over 16 years were included in the CHIRA database between 2016 and 2018. Patients were identified according to ICD-10 code. Descriptive analysis and log-linear analysis were conducted to examine the treatments of breast cancer. The project was commissioned with an ethical exemption. Findings: A total of 28,464 breast cancer patients aged 16 years and older who were diagnosed with breast cancer in China between January 2016 and December 2018 were included in this study. The mean age of 54.49 years, and the highest proportion of breast cancer patients were aged 50-60 years (30.66%). Approximately 72.54% of patients were covered by Urban Employee Basic Medical Insurance (EBMI). In this study, 73.56% of breast cancer patients utilized inpatient services, although, this study found the proportion of patients seeking medical treatment in lower-level hospitals increased over time, over 82.07% of the study population still seek care at tertiary hospitals in China. The cost of treatment decreased with increasing age and increased among patients treated at higher-level hospitals. Age, health insurance type, region, and hospital level were found to be associated with both total medical costs and out-of-pocket expenses for breast cancer patients. The annual total medical cost per capita decreased for outpatients and increased for inpatients over the three years. Inequities have been identified in financial protection for patients covered by different health insurance schemes and in different regions. Interpretation: The costs of breast cancer patients in China exhibit significant regional and demographic differences, with Chinese patients being significantly younger compared to those in other countries. Efforts in expanding breast cancer screening are necessary to reduce the disease severity and financial burden. Considering the variance in quality of care across different levels of hospitals, efforts should also be made to enhance the quality of care for cancer treatment in lower-level hospitals, and to ensure favorable health outcomes for patients. Funding: This study was funded by National Key Research and Development Program of China, National Natural Science Foundation of China, China Medical Board, the Royal Society.

OBJECTIVE:Mainstreaming genetic testing refers to genetic testing for cancer susceptibility genes following cancer diagnosis, which is provided by nongenetic health professionals of the cancer-treating team. Mainstreaming can be used to guide cancer treatment and secondary cancer prevention in the patient and to identify carriers in the family members of patients who test positive through cascade testing. We aimed to assess uptake and patient-reported outcomes of mainstreaming genetic testing. DATA SOURCES:We searched PubMed and the Cochrane Library from inception to June 2024. STUDY ELIGIBILITY CRITERIA:Our population included adult patients offered mainstreaming genetic testing (intervention). Outcomes included testing uptake, satisfaction, decisional conflict/regret, anxiety, depression, and cancer-related distress. STUDY APPRAISAL AND SYNTHESIS METHODS:We followed a prospective protocol according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines (International Prospective Register of Systematic Reviews: CRD42023467312). Qualitative synthesis and random effects meta-analyses were performed. Quality assessment was performed using the Methodological Index for Non-Randomized Studies. RESULTS:Searches yielded 5314 studies; 29 studies (n=13,219) were included, of which 14 were on ovarian cancer (n=6039), 6 on breast cancer (n=4354), 3 on prostate cancer (n=772), 1 on endometrial cancer (n=302), and 5 on multiple cancers (n=1752). There were no studies for colorectal cancer. Pooled genetic testing uptake was 91% (95% confidence interval=86-96, I2=99.6%, n=5942) across all cancers. Unselected testing uptake was 95% (95% confidence interval=92-98, I2=98.4%, n=3946), while family history/clinical criteria-based testing uptake was 80% (95% confidence interval=63-97, I2=99.0%, n=1996). Uptake for ovarian cancer cases was 93% (95% confidence interval=88-98, I2=98.6%, n=2801), for breast cancer 95% (95% confidence interval=90-99, I2=94.78%, n=981), for endometrial cancer 99% (95% confidence interval=98-100, I2=0.0%, n=304), and for prostate cancer 73% (95% confidence interval=47-99, I2=98.8%, n=772). Pooled pretest 24.24 (95% confidence interval: 23.34-24.14, I2=93.0%) and post-test 16.11 (95% confidence interval: 15.27-16.96, I2=80.3%). Decisional Conflict Scale scores were low (3 studies, n=681), decreasing from pretest to post-test (P=.03). On qualitative synthesis, pretest and post-test satisfaction scores were high (14 studies, n=3093). Decisional regret (4 studies, n=393), pretest and post-test depression scales (2 studies, n=252), and post-test distress (5 studies, n=773) were low. There was variability in reported pretest (low to high, 4 studies, n=1079) and post-test anxiety (low to moderate, 5 studies, n=1231) and pretest distress (low to moderate, 2 studies, n=594). CONCLUSION:Mainstreaming genetic testing uptake is associated with high uptake and satisfaction and low decision conflict, regret, and post-test distress. Quality and quantity of evidence across different types of cancers vary significantly.

Background:Population mental health in young people worsened during and since the COVID-19 pandemic. School environments can play a key role in improving young people's mental health. Learning Together for Mental Health is a whole-school intervention aiming to promote mental health and well-being among young people in secondary schools. Before progressing to a Phase III effectiveness evaluation of the intervention, it is critical to assess the feasibility of trial measures at baseline and follow-up. Objective:To evaluate the feasibility of trial measures and procedures within a feasibility study of a whole-school intervention aiming to promote mental health and well-being among young people in secondary schools, including whether we met our progression criterion of survey response rates of 60% or more in two or more schools at baseline and follow-up. Design and methods:We conducted a feasibility study which included assessment of the indicative primary and secondary outcomes measures and procedures to be used in a future Phase III trial. Setting and participants:Setting for our feasibility study included five state, mixed-sex secondary schools in southern England (one of which dropped out after baselines and one of which replaced this). We recruited year-7 students to participate in the baseline survey and year-10 students to participate in the follow-up survey at 12-month follow-up. Baseline and follow-up participants were different groups, as the focus was assessing feasibility of measures for the age groups that would be surveyed at baseline and follow-up in a Phase III randomised controlled trial. Our study was not powered or designed to estimate intervention effects. Interventions:As part of our feasibility study, all schools received the Learning Together for Mental Health intervention for one academic school year. Main outcome measures:The indicative primary outcome measure trialled was the total difficulties score of the Strengths and Difficulties Questionnaire. Indicative secondary outcomes measures trialled were the: Warwick-Edinburgh Mental Well-being Scale; Short Moods and Feelings Questionnaire; Generalised Anxiety Disorder-7 scale; Eating Disorders Examination - Questionnaire Short, self-harm (single item from the Health Behaviour in School-aged Children study); bullying victimisation (Gatehouse Bullying Scale); cyberbullying (two items adapted from the Dose Adjustment for Normal Eating II questionnaire); substance use (National Health Service measure); and Beyond Blue School Climate Questionnaire. Results:Trial measures and procedures were feasible to implement and were acceptable to year-7 and year-10 students, teachers and parents. At baseline, response rates ranged from 58% to 91% between schools. Only two students were opted out by parents, and no students opted out in advance. Students refusing consent on the day of survey was rare (7%). Twelve per cent of students were absent. The follow-up survey had an overall response rate of 66%, ranging from 44% to 91%. Only two students were opted out by parents, and three students opted out in advance. Overall, 12% opted out on the day. Twenty per cent of students were absent. Variation in response rate reflected specific problems at certain schools. Surveys took 40-45 minutes at baseline and 30 minutes at follow-up. The trial progression criterion concerning response rates was achieved, with three of four schools at baseline and two of four schools at follow-up having responses rates above 60%. Limitations:Our study involved a small, purposive sample of schools and students which are not representative of those in England. Conclusions:With some minor amendments, trial measures and procedures should be applied in a future Phase III effectiveness evaluation of the Learning Together for Mental Health intervention. Future work:Survey response rates could be improved if baseline and follow-up surveys are not scheduled in the last weeks of term, on Fridays or near mock General Certificate of Secondary Education exams. Completion of some measures (such as Eating Disorders Examination - Questionnaire Short) among year-7 students may be improved if question wording is tailored to be age-appropriate. Funding:This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme as award number NIHR131594.