Cost-Effectiveness of AI for Risk-Stratified Breast Cancer Screening.

Importance: Previous research has shown good discrimination of short-term risk using an artificial intelligence (AI) risk prediction model (Mirai). However, no studies have been undertaken to evaluate whether this might translate into economic gains. Objective: To assess the cost-effectiveness of incorporating risk-stratified screening using a breast cancer AI model into the United Kingdom (UK) National Breast Cancer Screening Program. Design, Setting, and Participants: This study, conducted from January 1, 2023, to January 31, 2024, involved the development of a decision analytical model to estimate health-related quality of life, cancer survival rates, and costs over the lifetime of the female population eligible for screening. The analysis took a UK payer perspective, and the simulated cohort consisted of women aged 50 to 70 years at screening. Exposures: Mammography screening at 1 to 6 yearly screening intervals based on breast cancer risk and standard care (screening every 3 years). Main Outcomes and Measures: Incremental net monetary benefit based on quality-adjusted life-years (QALYs) and National Health Service (NHS) costs (given in pounds sterling; to convert to US dollars, multiply by 1.28). Results: Artificial intelligence-based risk-stratified programs were estimated to be cost-saving and increase QALYs compared with the current screening program. A screening schedule of every 6 years for lowest-risk individuals, biannually and triennially for those below and above average risk, respectively, and annually for those at highest risk was estimated to give yearly net monetary benefits within the NHS of approximately £60.4 (US $77.3) million and £85.3 (US $109.2) million, with QALY values set at £20 000 (US $25 600) and £30 000 (US $38 400), respectively. Even in scenarios where decision-makers hesitate to allocate additional NHS resources toward screening, implementing the proposed strategies at a QALY value of £1 (US $1.28) was estimated to generate a yearly monetary benefit of approximately £10.6 (US $13.6) million. Conclusions and Relevance: In this decision analytical model study of integrating risk-stratified screening with a breast cancer AI model into the UK National Breast Cancer Screening Program, risk-stratified screening was likely to be cost-effective, yielding added health benefits at reduced costs. These results are particularly relevant for health care settings where resources are under pressure. New studies to prospectively evaluate AI-guided screening appear warranted.

Breast Cancer Screening Interval: Effect on Rate of Late-Stage Disease at Diagnosis and Overall Survival.

PURPOSE: Controversy continues regarding the effect of screening mammography on breast cancer outcomes. We evaluated late-stage cancer rate and overall survival (OS) for different screening intervals using a real-world institutional research data mart. METHODS: Patients having both a cancer registry record of new breast cancer diagnosis and prediagnosis screening history between 2004 and 2019 were identified from our institutional research breast data mart. Time interval between the two screening mammograms immediately preceding diagnosis and the time to cancer diagnosis were determined. Screening interval was deemed annual if ≤15 months, biennial if >15 and ≤27 months, intermittent if >27 months, and baseline if only one prediagnosis screen was known. The primary end point was late-stage cancer (TNM stage IIB or worse), and the secondary end point was OS. The association of screening interval and late-stage cancer was analyzed using multivariable logistic regression adjusting for prediagnosis characteristics. Proportional hazards regression was used for survival analysis. Potential lead time was analyzed using survival from a uniform fixed time point. RESULTS: In total, 8,145 patients with breast cancer had prediagnosis screening mammography in the timeframe. The percentage of late-stage cancers diagnosed increased significantly with screening interval with 9%, 14%, and 19% late stages for annual, biennial, and intermittent groups (P < .001), respectively. The trend persisted regardless of age, race, and menopausal status. Biennial and intermittent groups had substantially worse OS than the annual screened group, with relative hazards of 1.42 (95% CI, 1.11 to 1.82) and 2.69 (95% CI, 2.11 to 3.43), respectively, and 1.39 (95% CI, 1.08 to 1.78) and 2.01 (95% CI, 1.58 to 2.55) after adjustment for potential lead time. CONCLUSION: Annual mammographic screening was associated with lower risk of late-stage cancer and better OS across clinical and demographic subgroups. Our study suggests benefit of annual screening for women 40 years and older.

Evaluation of a Faith-Placed Health Education Service on Bowel Cancer Screening in Mosques in East London.

BACKGROUND: Bowel cancer screening using faecal immunochemical testing is provided in the United Kingdom with the aim of reducing mortality from colorectal cancer. However, there are low participant rates among ethnic minorities across the United Kingdom. Faith-placed interventions have the potential to improve screening rates among such populations, but studies examining their effectiveness are scarce. METHODS: We delivered a presentation on bowel cancer screening to 204 Muslims in seven mosques in East London (intervention group). All participants completed a questionnaire regarding attitudes, perceptions and knowledge of bowel cancer screening before and after the presentation. Concurrently, we administered the questionnaire to 72 subjects attending a mosque that did not receive the presentation (comparison group). RESULTS: The intervention group showed a greater willingness to do the test (90% vs. 67%, p < 0.001) and to recommend it to others (96% vs. 74%, p < 0.001), ability to complete the test by themselves (94% vs. 56%, p < 0.001) and confidence in noticing symptoms (78% vs. 32%, p < 0.001) after the presentation compared to before. There was a significant difference between the intervention group post-presentation and the comparison group on intention to do the test (90% vs. 79%, p = 0.02), recommending it to others (96% vs. 83%, p < 0.001), and confidence in their ability to complete the test by themselves (94% vs. 63%, p < 0.001). CONCLUSION: A culture-sensitive, faith-placed health education intervention delivered in mosques can substantially improve knowledge of bowel cancer screening and increase the intention to participate in the screening programme. PATIENT OR PUBLIC CONTRIBUTION: The intervention presentation was developed using insights from four public involvement sessions with four to six members representative of the East London Muslim community. The sessions sought attendees' thoughts on appropriate ways to approach the intervention design for their community and asked for their views on the acceptability, appropriateness of messaging, format/design and likely impact of the presentation. Their views were then utilised to improve the presentation.

Associations Between Dual Antiplatelet Therapy Score and Long-Term Mortality After Percutaneous Coronary Intervention: Analysis of More Than 27,000 Patients.

BACKGROUND: The dual antiplatelet therapy (DAPT) score was developed to identify patients undergoing percutaneous coronary intervention (PCI) who are likely to derive benefit (score ≥ 2) or harm (score < 2) from extended DAPT beyond 1 year after PCI in terms of ischemic and bleeding outcomes. We examined the associations between DAPT score at index PCI and long-term mortality from an all-comers PCI registry in patients receiving DAPT according to the standard of care. METHODS: We retrospectively examined prospectively collected data from the Melbourne Interventional Group PCI database (2005-2018) and grouped patients as having DAPT score ≥ 2 or < 2. Long-term mortality was assessed from the Australian National Death Index linkage. The primary end point was long-term mortality as determined using survival analysis. Secondary end points included in-hospital events and 30-day major adverse cardiac events (MACE), a composite of death, myocardial infarction, or target vessel revascularisation. RESULTS: Of 27,740 study patients, 9402 (33.9%) had DAPT score ≥ 2. Patients with DAPT score ≥ 2 were younger, included more women, and had a higher prevalence of cardiovascular risk factors. Patients with DAPT score ≥ 2 had higher in-hospital mortality (3.0% vs 1.0%), major bleeding (2.3% vs 1.6%), 30-day MACE (7.1% vs 3.1%), and long-term mortality at a median follow-up of 5.17 years (21.9% vs 16.5%) P < 0.001 for all. CONCLUSIONS: One-third of all-comer patients undergoing PCI had a DAPT score ≥ 2 with greater short-term ischemic and bleeding risk, and higher long-term mortality. Risk assessment with the DAPT score may guide the duration and intensity of DAPT beyond the early post-PCI period.

Long-term effects of once-only flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: 21-year follow-up of the UK Flexible Sigmoidoscopy Screening randomised controlled trial.

BACKGROUND: Flexible sigmoidoscopy screening reduces colorectal cancer incidence and mortality; however, uncertainty exists about the duration of protection and differences by sex and age. We assessed effects of once-only flexible sigmoidoscopy screening after 21 years' follow-up. METHODS: The UK Flexible Sigmoidoscopy Screening Trial is a multicentre randomised controlled trial that recruited men and women aged 55-64 years from general practices serving 14 hospitals. Among participants indicating that they would attend flexible sigmoidoscopy screening if invited, randomisation (2:1) to the control (no further contact) or intervention (invited to once-only flexible sigmoidoscopy screening) group was performed centrally in blocks of 12, stratified by centre, general practice, and household type. Masking of intervention was infeasible. Primary outcomes were colorectal cancer incidence and mortality. The Kaplan-Meier method estimated cumulative incidence. Primary analyses estimated intention-to-treat hazard ratios (HRs) and risk differences, overall and stratified by subsite, sex, and age. The trial is registered with ISRCTN, number 28352761. FINDINGS: Among participants recruited between Nov 14, 1994, and March 30, 1999, 170 432 were eligible and 113 195 were randomly assigned to the control group and 57 237 were randomly assigned to the intervention group. 406 participants were excluded from analyses (268 in the control group and 138 in the intervention group), leaving 112 927 participants in the control group (55 336 [49%] men and 57 591 [51%] women) and 57 099 in the intervention group (27 966 [49%] men and 29 103 [51%] women). Of participants who were invited to be screened, 40 624 (71%) attended screening. Median follow-up was 21·3 years (IQR 18·0-22·2). In the invited-to-screening group, colorectal cancer incidence was reduced compared with the control group (1631 vs 4201 cases; cumulative incidence at 21 years was 3·18% [95% CI 3·03 to 3·34] vs 4·16% [4·04 to 4·29]; HR 0·76 [95% CI 0·72 to 0·81]) with 47 fewer cases per 100 000 person-years (95% CI -56 to -37). Colorectal cancer mortality was also reduced in the invited-to-screening group compared with the control group (502 vs 1329 deaths; cumulative incidence at 21 years was 0·97% [0·88 to 1·06] vs 1·33% [1·26 to 1·40]; HR 0·75 [0·67 to 0·83]) with 16 fewer deaths per 100 000 person-years (-21 to -11). Effects were particularly evident in the distal colorectum (726 incident cancer cases in the invited-to-screening group vs 2434 cases in the control group; HR 0·59 [0·54 to 0·64]; 47 fewer cases per 100 000 person-years [-54 to -41]; 196 cancer deaths in the invited-to-screening group vs 708 deaths in the control group; HR 0·55 [0·47 to 0·64]; 15 fewer deaths per 100 000 person-years [-19 to -12]) and not the proximal colon (871 incident cancer cases in the invited-to-screening group vs 1749 cases in the control group; HR 0·98 [0·91 to 1·07]; one fewer case per 100 000 person-years [-8 to 5]; 277 cancer deaths in the invited-to-screening group vs 547 deaths in the control group; HR 1·00 [0·86 to 1·15]; zero fewer deaths per 100 000 person-years [-4 to 4]). The HR for colorectal cancer incidence was lower in men (0·70 [0·65-0·76]) than women (0·86 [0·79 to 0·93]; pinteraction=0·0007) but there was no difference by age. INTERPRETATION: We show that once-only flexible sigmoidoscopy screening reduces colorectal cancer incidence and mortality for two decades and provide important data to inform colorectal cancer screening guidelines. FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme and the Medical Research Council.

Comparing the effectiveness and cost-effectiveness of text-message reminders and telephone patient navigation to improve the uptake of faecal immunochemical test screening among non-responders in London: a randomised controlled trial protocol.

INTRODUCTION: Participation in bowel cancer screening is lower in regions where there is high ethnic diversity and/or socioeconomic deprivation. Interventions, such as text message reminders and patient navigation (PN), have the potential to increase participation in these areas. As such, there is interest in the comparative effectiveness of these interventions to increase bowel cancer screening participation, as well as their relative cost-effectiveness. METHODS AND ANALYSIS: This study will use a three-arm randomised controlled trial design to compare the effectiveness and cost-effectiveness of text message reminders and PN to increase the uptake of bowel cancer screening in London. Participants will be individuals who have not returned a completed faecal immunochemical test kit within 13 weeks of receiving a routine invitation from the London bowel cancer screening hub. Participants will be randomised (in a 1:1:1 ratio) to receive either (1) usual care (ie, 'no intervention'), (2) a text message reminder at 13 weeks, followed by repeated text message reminders at 15, 17 and 19 weeks (in the event of non-response) or (3) a text message reminder at 13 weeks, followed by PN telephone calls at 15, 17 and 19 weeks in the event of non-response. The primary endpoint will be participation in bowel cancer screening, defined as 'the return of a completed kit by week 24'. Statistical analysis will use multivariate logistic regression and will incorporate pairwise comparisons of all three groups, adjusted for multiple testing. ETHICS AND DISSEMINATION: Approvals to conduct the research have been obtained from University College London's Joint Research Office (Ref: 150666), the Screening Research, Innovation and Development Advisory Committee ('RIDAC', Ref: 2223 014 BCSP Kerrison), the Health Research Authority (Ref: 22/WM/0212) and the Confidentiality Advisory Group (Ref: 22/CAG/0140). Results will be conveyed to stakeholders, notably those managing the screening programme and published in peer-reviewed journals/presented at academic conferences. TRIAL REGISTRATION NUMBER: ISRCTN17245519.

Strong association between reduction of late-stage cancers and reduction of cancer-specific mortality in meta-regression of randomized screening trials across multiple cancer types.

BACKGROUND: Late-stage cancer incidence has been proposed as an early surrogate for mortality in randomized controlled trials (RCTs) of cancer screening; however, its validity has not been systematically evaluated across screening RCTs of different cancers. METHODS: We conducted a meta-regression analysis of cancer screening RCTs that reported both late-stage cancer incidence and cancer mortality. Based on a systematic literature review, we included 33 RCTs of screening programs targeting seven cancer types, including lung (n = 12), colorectal (n = 8), breast (n = 5), and prostate (n = 4), among others. We regressed the relative reduction of cancer mortality on the relative reduction of late-stage cancer incidence, inversely weighted for each RCT by the variance of estimated mortality reduction. RESULTS: Across cancer types, the relative reduction of late-stage cancer incidence was linearly associated with the relative reduction of cancer mortality. Specifically, we observed this association for lung (R2 = 0.79 and 0.996 in three recent large trials), breast (R2 = 0.94), prostate (R2 = 0.98), and colorectal cancer (R2 = 0.75 for stage III/IV cancers and 0.93 for stage IV cancers). Trials with a 20% or greater reduction in late-stage cancers were more likely to achieve a significant reduction in cancer mortality. Our results also showed that no reduction of late-stage cancer incidence was associated with no or minimal reduction in cancer mortality. CONCLUSIONS: Meta-regression of historical screening RCTs showed a strong linear association between reductions in late-stage cancer incidence and cancer mortality.

Impact of single round of low dose CT lung cancer screening on cause of mortality in different socio-economic groups: a post-hoc analysis of long-term follow-up of the UKLS trial.

Background: Lower socioeconomic status, as measured by the Index of Multiple Deprivation (IMD), is associated with higher rates of smoking-related disease mortality, and with poor uptake of cancer screening. Here we explore whether socioeconomic status impacts the effectiveness of a single round of low-dose-CT screening, or impacts other causes of death, in the UKLS LDCT screening trial. Methods: IMD quintiles were defined according to UK-wide data, with the deprived group defined as the lower two quintiles (Q1-2) and the less deprived as Q3-5. Follow-up data was obtained for lung cancer diagnosis (median follow-up 9.1 years) and cause of death (median follow-up 9.9 years). Outcomes were compared based on IMD group and trial arm (CT or control). Findings: More deprived quintiles were less likely to respond to the questionnaire, but this population was more likely to be selected for screening by the LLP risk model. Lower IMD quintiles benefitted from low-dose-CT screening in terms of lung cancer survival (HR 1.89, 95% CI 1.16-3.08) to the same extent as upper quintiles (HR 1.87, 95% CI 1.07-3.26). However, there was a bigger impact on deaths due to COPD and emphysema in more deprived quintiles. Interpretation: Whilst LDCT screening benefit for lung cancer was similar, significant impact on the rates of death from other smoking-related diseases, notably COPD and emphysema, was seen primarily in lower socioeconomic groups. Future research is required to confirm how lung cancer screening benefits other disease outcomes. Funding: NIHR Health Technology Assessment Programme; NIHR Policy Research programme; Roy Castle Lung Cancer Foundation.

Associations Between Metabolic Syndrome and Long-Term Mortality in Patients who underwent Percutaneous Coronary Intervention: An Australian Cohort Analysis.

Metabolic syndrome (MetS) provides significant risk for coronary disease, however long-term prognosis after percutaneous coronary intervention (PCI) has been understudied. We assessed the prevalence and outcomes of patients with MetS from an Australian PCI cohort. We retrospectively examined data from the Melbourne Interventional Group multicenter PCI registry using a modified definition for MetS including ≥3 of the following: hypertension, diabetes mellitus, dyslipidemia, and body mass index ≥30 kg/m2. Thirty-day outcomes and long-term mortality were compared with patients without MetS. Cox regression methods were used to assess the multivariable effect of MetS on long-term mortality. Of 41,146 patients, 12,228 (34%) had MetS. Patients with MetS experienced greater 30-day myocardial infarction (2.2% vs 1.8%, p = 0.013), whereas patients without MetS had a trend for greater 30-day mortality (3.0% vs 3.4%, p = 0.051) and greater in-hospital major bleeding (1.7% vs 2.4%, p <0.001). After a median follow-up of 5.62 years (Q1 2.03, Q3 8.89), patients with MetS experienced greater mortality (24% vs 19%, p <0.001). After adjustment, MetS was not an independent predictor of long-term mortality (hazard ratio 0.95 confidence interval 0.86 to 1.05, p = 0.35). In sensitivity analyses, MetS-Diabetic patients had the highest, and MetS-NonDiabetic obese patients had the lowest long-term mortality. One in 3 patients who underwent all-comer PCI presented with MetS and experienced greater long-term mortality compared with others. However, this association was lost after adjustment for baseline confounders, highlighting that MetS is a marker of risk after PCI. Our findings support the obesity paradox and confirm robust associations between diabetes mellitus and long-term mortality.

Cost-Effectiveness of Gene-Specific Prevention Strategies for Ovarian and Breast Cancer.

Importance: Pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 cancer susceptibility genes (CSGs) confer an increased ovarian cancer (OC) risk, with BRCA1, BRCA2, PALB2, RAD51C, and RAD51D PVs also conferring an elevated breast cancer (BC) risk. Risk-reducing surgery, medical prevention, and BC surveillance offer the opportunity to prevent cancers and deaths, but their cost-effectiveness for individual CSGs remains poorly addressed. Objective: To estimate the cost-effectiveness of prevention strategies for OC and BC among individuals carrying PVs in the previously listed CSGs. Design, Setting, and Participants: In this economic evaluation, a decision-analytic Markov model evaluated the cost-effectiveness of risk-reducing salpingo-oophorectomy (RRSO) and, where relevant, risk-reducing mastectomy (RRM) compared with nonsurgical interventions (including BC surveillance and medical prevention for increased BC risk) from December 1, 2022, to August 31, 2023. The analysis took a UK payer perspective with a lifetime horizon. The simulated cohort consisted of women aged 30 years who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. Appropriate sensitivity and scenario analyses were performed. Exposures: CSG-specific interventions, including RRSO at age 35 to 50 years with or without BC surveillance and medical prevention (ie, tamoxifen or anastrozole) from age 30 or 40 years, RRM at age 30 to 40 years, both RRSO and RRM, BC surveillance and medical prevention, or no intervention. Main Outcomes and Measures: The incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained. OC and BC cases and deaths were estimated. Results: In the simulated cohort of women aged 30 years with no cancer, undergoing both RRSO and RRM was most cost-effective for individuals carrying BRCA1 (RRM at age 30 years; RRSO at age 35 years), BRCA2 (RRM at age 35 years; RRSO at age 40 years), and PALB2 (RRM at age 40 years; RRSO at age 45 years) PVs. The corresponding ICERs were -£1942/QALY (-$2680/QALY), -£89/QALY (-$123/QALY), and £2381/QALY ($3286/QALY), respectively. RRSO at age 45 years was cost-effective for RAD51C, RAD51D, and BRIP1 PV carriers compared with nonsurgical strategies. The corresponding ICERs were £962/QALY ($1328/QALY), £771/QALY ($1064/QALY), and £2355/QALY ($3250/QALY), respectively. The most cost-effective preventive strategy per 1000 PV carriers could prevent 923 OC and BC cases and 302 deaths among those carrying BRCA1; 686 OC and BC cases and 170 deaths for BRCA2; 464 OC and BC cases and 130 deaths for PALB2; 102 OC cases and 64 deaths for RAD51C; 118 OC cases and 76 deaths for RAD51D; and 55 OC cases and 37 deaths for BRIP1. Probabilistic sensitivity analysis indicated both RRSO and RRM were most cost-effective in 96.5%, 89.2%, and 84.8% of simulations for BRCA1, BRCA2, and PALB2 PVs, respectively, while RRSO was cost-effective in approximately 100% of simulations for RAD51C, RAD51D, and BRIP1 PVs. Conclusions and Relevance: In this cost-effectiveness study, RRSO with or without RRM at varying optimal ages was cost-effective compared with nonsurgical strategies for individuals who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. These findings support personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC risk management.

Comparing accuracy of tomosynthesis plus digital mammography or synthetic 2D mammography in breast cancer screening: baseline results of the MAITA RCT consortium.

AIM: The analyses here reported aim to compare the screening performance of digital tomosynthesis (DBT) versus mammography (DM). METHODS: MAITA is a consortium of four Italian trials, REtomo, Proteus, Impeto, and MAITA trial. The trials adopted a two-arm randomised design comparing DBT plus DM (REtomo and Proteus) or synthetic-2D (Impeto and MAITA trial) versus DM; multiple vendors were included. Women aged 45 to 69 years were individually randomised to one round of DBT or DM. FINDINGS: From March 2014 to February 2022, 50,856 and 63,295 women were randomised to the DBT and DM arm, respectively. In the DBT arm, 6656 women were screened with DBT plus synthetic-2D. Recall was higher in the DBT arm (5·84% versus 4·96%), with differences between centres. With DBT, 0·8/1000 (95% CI 0·3 to 1·3) more women received surgical treatment for a benign lesion. The detection rate was 51% higher with DBT, ie. 2·6/1000 (95% CI 1·7 to 3·6) more cancers detected, with a similar relative increase for invasive cancers and ductal carcinoma in situ. The results were similar below and over the age of 50, at first and subsequent rounds, and with DBT plus DM and DBT plus synthetic-2D. No learning curve was appreciable. Detection of cancers >= 20 mm, with 2 or more positive lymph nodes, grade III, HER2-positive, or triple-negative was similar in the two arms. INTERPRETATION: Results from MAITA confirm that DBT is superior to DM for the detection of cancers, with a possible increase in recall rate. DBT performance in screening should be assessed locally while waiting for long-term follow-up results on the impact of advanced cancer incidence.

Effects on Cancer Prevention from the COVID-19 Pandemic.

The COVID-19 pandemic led to disruption of health services around the world, including cancer services. We carried out a narrative review of the effect of the pandemic on cancer prevention services, including screening. Services were severely affected in the early months of the pandemic, and in some areas are still recovering. Large numbers of additional cancers or additional late-stage cancers have been predicted to arise over the coming years as a result of this disruption. To minimize the effects on cancer outcomes, it is necessary to return as quickly as possible to prepandemic levels of screening and prevention activity or indeed to exceed these levels. The recovery of services should address health inequalities.

Beneficial effect of repeated participation in breast cancer screening upon survival.

OBJECTIVES: The benefit of mammography screening in reducing population mortality from breast cancer is well established. In this paper, we estimate the effect of repeated participation at scheduled screens on case survival. METHODS: We analysed incidence and survival data on 37,079 women from nine Swedish counties who had at least one to five invitation(s) to screening prior to diagnosis, and were diagnosed with breast cancer between 1992 and 2016. Of these, 4564 subsequently died of breast cancer. We estimated the association of survival with participation in up to the most recent five screens before diagnosis. We used proportional hazards regression to estimate the effect on survival of the number of scheduled screens in which subjects participated prior to the diagnosis of breast cancer. RESULTS: There was successively better survival with an increasing number of screens in which the subject participated. For a woman with five previous screening invitations who participated in all five, the hazard ratio was 0.28 (95% confidence interval (CI) 0.25-0.33, p < 0.0001) compared to a woman attending none (86.9% vs 68.9% 20-year survival). Following a conservative adjustment for potential self-selection factors, the hazard ratio was 0.34 (95% CI 0.26-0.43, p < 0.0001), an approximate three-fold reduction in the hazard of dying from breast cancer. CONCLUSION: For those women who develop breast cancer, regular prior participation in mammography screening confers significantly better survival.

An optimization framework to guide the choice of thresholds for risk-based cancer screening.

It is uncommon for risk groups defined by statistical or artificial intelligence (AI) models to be chosen by jointly considering model performance and potential interventions available. We develop a framework to rapidly guide choice of risk groups in this manner, and apply it to guide breast cancer screening intervals using an AI model. Linear programming is used to define risk groups that minimize expected advanced cancer incidence subject to resource constraints. In the application risk stratification performance is estimated from a case-control study (2044 cases, 1:1 matching), and other parameters are taken from screening trials and the screening programme in England. Under the model, re-screening in 1 year for the highest 4% AI model risk, in 3 years for the middle 64%, and in 4 years for 32% of the population at lowest risk, was expected to reduce the number of advanced cancers diagnosed by approximately 18 advanced cancers per 1000 diagnosed with triennial screening, for the same average number of screens in the population as triennial screening for all. Sensitivity analyses found the choice of thresholds was robust to model parameters, but the estimated reduction in advanced cancers was not precise and requires further evaluation. Our framework helps define thresholds with the greatest chance of success for reducing the population health burden of cancer when used in risk-adapted screening, which should be further evaluated such as in health-economic modelling based on computer simulation models, and real-world evaluations.

A plea for more careful scholarship in reviewing evidence: the case of mammographic screening.

Objectives: To identify issues of principle and practice giving rise to misunderstandings in reviewing evidence, to illustrate these by reference to the Nordic Cochrane Review (NCR) and its interpretation of two trials of mammographic screening, and to draw lessons for future reviewing of published results. Methods: A narrative review of the publications of the Nordic Cochrane Review of mammographic screening (NCR), the Swedish Two-County Trial (S2C) and the Canadian National Breast Screening Study 1 and 2 (CNBSS-1 and CNBSS-2). Results: The NCR concluded that the S2C was unreliable, despite the review's complaints being shown to be mistaken, by direct reference to the original primary publications of the S2C. Repeated concerns were expressed by others about potential subversion of randomisation in CNBSS-1 and CNBSS-2; however, the NCR continued to rely heavily on the results of these trials. Since 2022, however, eyewitness evidence of such subversion has been in the public domain. Conclusions: An over-reliance on nominal satisfaction of checklists of criteria in systematic reviewing can lead to erroneous conclusions. This occurred in the case of the NCR, which concluded that mammographic screening was ineffective or minimally effective. Broader and more even-handed reviews of the evidence show that screening confers a substantial reduction in breast cancer mortality. Advances in knowledge: Those carrying out systematic reviews should be aware of the dangers of over-reliance on checklists and guidelines. Readers of systematic reviews should be aware that a systematic review is just another study, with the capability that all studies have of coming to incorrect conclusions. When a review seems to overturn the current position, it is essential to revisit the publications of the primary research.

Sex Differences in Pharmacotherapy and Long-Term Outcomes in Patients With Ischaemic Heart Disease and Comorbid Left Ventricular Dysfunction.

BACKGROUND: Left ventricular (LV) dysfunction and ischaemic heart disease (IHD) are common among women. However, women tend to present later and are less likely to receive guideline-directed medical therapy (GDMT) compared with men. METHODS: We analysed prospectively collected data (2005-2018) from a multicentre registry on GDMT 30 days after percutaneous coronary intervention in 13,015 patients with LV ejection fraction <50%. Guideline-directed medical therapy was defined as beta blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker±mineralocorticoid receptor antagonist. Long-term mortality was determined by linkage with the Australian National Death Index. RESULTS: Women represented 20% (2,634) of the total cohort. Mean age was 65±12 years. Women were on average >5 years, with higher body mass index and higher rates of hypertension, diabetes, renal dysfunction, prior stroke, and rheumatoid arthritis. Guideline-directed medical therapy was similar between sexes (73% vs 72%; p=0.58), although women were less likely to be on an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (80% vs 82%; p=0.02). Women were less likely to be on statin therapy (p<0.001) or a second antiplatelet agent (p=0.007). Women had higher unadjusted long-term mortality (25% vs 19%; p<0.001); however, there were no differences in long-term mortality between sexes on adjusted analysis (hazard ratio 0.99; 95% confidence interval 0.87-1.14; p=0.94). CONCLUSIONS: Rates of GDMT for LV dysfunction were high and similar between sexes; however, women were less likely to be on appropriate IHD secondary prevention. The increased unadjusted long-term mortality in women was attenuated in adjusted analysis, which highlights the need for optimisation of baseline risk to improve long-term outcomes of women with IHD and comorbid LV dysfunction.

The cost-effectiveness of risk-stratified breast cancer screening in the UK.

BACKGROUND: There has been growing interest in the UK and internationally of risk-stratified breast screening whereby individualised risk assessment may inform screening frequency, starting age, screening instrument used, or even decisions not to screen. This study evaluates the cost-effectiveness of eight proposals for risk-stratified screening regimens compared to both the current UK screening programme and no national screening. METHODS: A person-level microsimulation model was developed to estimate health-related quality of life, cancer survival and NHS costs over the lifetime of the female population eligible for screening in the UK. RESULTS: Compared with both the current screening programme and no screening, risk-stratified regimens generated additional costs and QALYs, and had a larger net health benefit. The likelihood of the current screening programme being the optimal scenario was less than 1%. No screening amongst the lowest risk group, and triannual, biennial and annual screening amongst the three higher risk groups was the optimal screening strategy from those evaluated. CONCLUSIONS: We found that risk-stratified breast cancer screening has the potential to be beneficial for women at the population level, but the net health benefit will depend on the particular risk-based strategy.

Impact of Preprocedural Diastolic Blood Pressure on Outcomes in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Recent US guidelines recommend lower blood pressure (BP) targets in hypertension, but aggressive lowering of diastolic BP (DBP) can occur at the expense of myocardial perfusion, particularly in the presence of coronary artery disease. We sought to establish the long-term impact of low DBP on mortality among patients undergoing percutaneous coronary intervention with well-controlled systolic BP. METHODS: We analyzed data from 12 965 patients undergoing percutaneous coronary intervention between 2009 and 2018 from the Melbourne Interventional Group registry who had a preprocedural systolic BP of ≤140 mm Hg. Patients with ST-elevation myocardial infarction, cardiogenic shock, and out-of-hospital arrest were excluded. Patients were stratified into 5 groups according to preprocedural DBP: <50, 50 to 59, 60 to 69, 70 to 79, and ≥80 mm Hg. The primary outcome was long-term, all-cause mortality. Mortality data were derived from the Australian National Death Index. RESULTS: Patients with DBP<50 mm Hg were older with higher rates of diabetes, renal impairment, prior myocardial infarction, left ventricular dysfunction, peripheral and cerebrovascular disease (all P<0.001). Patients with DBP<50 mm Hg had higher 30-day (2.5% versus 0.7% for the other 4 quintiles; P<0.0001) and long-term mortality (median, 3.6 years; follow-up, 29% versus 11%; P<0.0001). Cox-regression analysis revealed that DBP<50 mm Hg was an independent predictor of long-term mortality (hazard ratio [HR], 1.55 [95% CI, 1.20-2.00]; P=0.001). CONCLUSIONS: In patients with well-controlled systolic BP undergoing percutaneous coronary intervention, low DBP (<50 mm Hg) is an independent predictor of long-term mortality.

Reply to Yaffe, M.J. Correction for Self-Selection in Breast Cancer Screening. Comment on "Dibden et al. Worldwide Review and Meta-Analysis of Cohort Studies Measuring the Effect of Mammography Screening Programmes on Incidence-Based Breast Cancer Mortality. Cancers 2020, 12, 976".

In his Comment [...].