BACKGROUND:There is conflicting evidence regarding the merits of patellar resurfacing during total knee replacement (TKR), as previous randomised controlled trials (RCTs) have been under-powered and with follow-up of ten years or less. METHODS:A pragmatic, multicentre, open-label RCT was initiated in 1999 in the UK. Within a partial-factorial design, participants were randomly allocated to receive or not receive patellar resurfacing during primary TKR and were followed up for 20 years. Adult (aged ≥18 years) patients due to have a primary TKR under the care of a collaborating surgeon were eligible. Participants were allocated (1:1) using an automated telephone service stratified by surgeon, with minimisation according to the patients' age (<60 years, 60-79 years, ≥80 years), sex, and location of d isease. The primary outcome measure was the Oxford Knee Score (OKS), analysed using repeated measures mixed-effects linear regression analysis with marginal differences reported. Secondary measures included the 12-Item Short Form Health Survey (SF-12), the European Quality of Life 5-Dimensions 3-Levels (EQ-5D-3L), costs, cost-effectiveness, and subsequent knee surgery. This trial is registered with ISRCTN Registry, ISRCTN45837371. FINDINGS:Between April 8, 1999, and Jan 13, 2003, 1715 participants (955 female and 760 male; mean age 70 years [SD 8], mean BMI 29·7 kg/m2) were randomly assigned: 861 to patellar resurfacing and 854 to no resurfacing. At the 20-year follow-up, 132 participants in the patellar resurfacing group and 110 participants in the non-resurfacing group provided outcome data, although marginal differences included earlier data for participants who died or had missing 20-year data. The marginal difference in OKS over the whole 20-year follow-up was 0·76 (95% CI -0·08 to 1·59; p=0·076) in favour of patellar resurfacing. During the 20-year follow-up period, although not significant, differences in OKS, SF-12, and EQ-5D-3L, readmissions, minor or intermediate operations, patella-related operations, major operations, and complications all favoured patellar resurfacing. At 20 years, the resurfaced group accrued significantly more quality-adjusted life-years (QALYs) than the non-resurfaced group (7·295 vs 6·884; difference 0·380, 95% CI 0·061 to 0·700; p=0·020). However, QALY differences were smaller in a sensitivity analysis assuming no difference in mortality (7·209 vs 6·964; difference 0·183, 95% CI -0·034 to 0·400; p=0·10). The cost of readmissions was non-significantly lower in the resurfaced group and offset the higher cost of primary TKR; therefore, overall 20-year health-care costs per participant were similar (£10 825 vs £10 889; difference -£6, 95% CI -£721 to £708; p=0·99). INTERPRETATION:There was no significant difference in primary outcome (OKS) or other clinical endpoints. However, as clinical differences tend to support patellar resurfacing, the resurfacing group had significantly higher QALYs. There was no difference in costs over the 20-year period, and patellar resurfacing had a 99% probability of being cost-effective at any threshold above £10 000 per QALY gained. The evidence is therefore weighted towards resurfacing being the approach of first choice. FUNDING:UK National Institute for Health and Care Research Health Technology Assessment Programme.

Background and Purpose Mechanical thrombectomy (MT) is a cost-effective treatment for large-vessel occlusion stroke. However, existing economic evaluations rely on restrictive assumptions regarding care pathways and resource use, limiting their applicability to real-world implementation. We evaluated the cost and cost-effectiveness implications of implementing MT across alternative, empirically observed clinical pathways in England to address this source of decision uncertainty. Methods A state-transition Markov model was populated with detailed United Kingdom clinical, outcome, and micro-costing data from five thrombectomy centres in England to compare MT with standard care. Alternative implementation scenarios reflected real-world variation in treatment pathways, including intervention-centre type, anaesthesia use, intensive care unit setting, and models of care. Scenarios were characterised using detailed pathway and cost data. Costs and quality-adjusted life-years were evaluated over a 5-year time horizon from National Health Service and societal perspectives. Results Mean procedural costs for MT were £6,135 (95% CI, £5,961-£6,318) per patient in the primary analysis, compared with £7,283 in the earlier protocol-based model. Over 5 years, MT was a dominant intervention, associated with both lower costs and improved health outcomes compared with standard care. Mean cost savings were £2,297 per patient, corresponding to an estimated annual saving of £52.6 million if all 22,908 potentially eligible patients were treated. Across all five centres and implementation scenarios, incremental cost-effectiveness ratios consistently remained below currently accepted willingness-to-pay thresholds per quality-adjusted life-year gained. Conclusions Across a range of real-world clinical pathways, MT is highly likely to be a cost-saving alternative to current practice and cost-effective at current health opportunity-cost thresholds. These findings suggest that cost-effectiveness is robust to local variation in service delivery and support broader implementation of MT within the English stroke-care system.

BACKGROUND:Screening for anxiety problems in primary schools and offering parent-led cognitive behavioural therapy (CBT) via online and telephone support for those who screen positive could address key barriers to effective early intervention for some of the most prevalent child mental disorders. We aimed to evaluate outcomes from a screening-to-intervention pathway for child anxiety problems alongside usual school provision compared with assessment and usual school provision only. METHODS:iCATSi2i was a pragmatic, parallel-group, superiority, cluster-randomised, controlled trial in 84 primary and junior schools in England with at least two year-4 classes. Children aged 8-9 years in participating classes who were not opted out by their parent were eligible to participate. After baseline assessments, schools (clusters) were randomly assigned (1:1) to screening, feedback, and intervention, alongside usual school practice (intervention group) or assessment and usual school practice only (control group), stratified by school-level deprivation. Before allocation, schools were ordered by the number of children who screened positive for anxiety problems at baseline (target population). Block randomisation was used with block sizes of two and four. Trial statisticians were masked to group allocation until datasets were ready for final analysis. In schools in the intervention group all parents in sampled classes were invited to complete a two-item screening questionnaire (iCATS-2) at baseline and received feedback on the screening outcome (after randomisation); parents of children who screened positive for anxiety problems (target population) were offered parent-led CBT delivered via online and telephone support, using the Online Support and Intervention for Child Anxiety (OSI) platform (and this was available for other families on request); a single whole-class session on identifying and managing fears and worries was also provided. In both groups, assessments (including the screening questionnaire) were completed and schools continued with usual provision. The primary outcome was screen-negative for anxiety problems (score 0-2 on the parent-reported iCATS-2) versus screen-positive (score 3-6) in the target population at 12 months. Primary analyses were conducted in the intention-to-treat population, with missing data imputed. Adverse events were monitored and recorded throughout. The trial was registered with the ISRCTN registry, ISRCTN76119074, and the study is complete. The study management group included individuals with relevant lived experience. FINDINGS:We recruited participants and collected baseline assessments between Jan 6, and Nov 30, 2022. Parents of 1459 children (27% of 5335 children in participating classes) completed the screening questionnaire, and 409 screened positive (target population). On the basis of parent report, 222 (54%) of 408 children who screened positive were female, 185 (45%) were male, and one (<1%) preferred not to report child gender. 325 (85%) of 384 children were reported by the school as White. The mean age was 8·8 years (SD 0·3). 42 schools were randomly assigned to the intervention group (target population: 205 children) and 42 to the control group (target population: 204 children). In the target population at 12 months, more children screened negative for anxiety problems in the intervention group (89 [61%] of 145 children) than the control group (62 [38%] of 163 children), with an adjusted odds ratio of 2·32 (95% CI 1·41-3·81; p=0·0009) in the primary analysis based on imputed data. No serious adverse events related to trial procedures or the intervention or adverse events related to the intervention were reported. INTERPRETATION:An integrated screening-to-intervention pathway for child anxiety problems in primary schools reduced parent-reported child anxiety problems compared with assessment and usual provision only, providing a promising way to improve access to effective early intervention. FUNDING:National Institute for Health and Care Research Programme Grants for Applied Research.

INTRODUCTION:Anxiety problems are prevalent in childhood and, without intervention, can persist into adulthood. Effective evidence-based interventions for childhood anxiety disorders exist, specifically cognitive-behavioural therapy (CBT) in a range of formats. However, only a small proportion of children successfully access and receive treatment. Conducting mental health screening in schools and integrating evidence-based interventions for childhood anxiety problems may be an effective way to ensure support reaches children in need. The Identifying Child Anxiety Through Schools-Identification to Intervention (iCATS i2i) trial involves screening for childhood anxiety problems and offering a brief online parent-led CBT intervention. This paper presents the protocol for the process evaluation of the iCATS i2i trial, which aims to examine the implementation and acceptability of the study procedures, the mechanisms of change and whether any external factors had an impact on procedure engagement or delivery. METHODS AND ANALYSIS:This process evaluation will use both quantitative and qualitative methods to evaluate the implementation and acceptability of and barriers/facilitators to engagement and delivery of the iCATS screening/intervention procedures. Quantitative data sources will include opt-out and completion rates of baseline measures and usage analytics extracted from the online intervention platform. Qualitative interviews will be conducted with children, parents, school staff, iCATS i2i clinicians and researchers delivering study procedures. The Medical Research Council framework for process evaluations will guide study design and analysis. ETHICS AND DISSEMINATION:This study has received ethical approval from the University of Oxford Research Ethics Committee (R66068_RE003). Findings from the study will be disseminated via peer-reviewed publications in academic journals, conferences, digital and social media platforms and stakeholder meetings. TRIAL REGISTRATION:ISRCTN76119074.

Timely diagnosis of dementia is a public health priority to enable risk modification and treatment access. This study systematically identifies and critically appraises health economic models of dementia assessment and diagnosis. Inclusion criteria were: any dementia stage; evaluated strategy(ies) for initial assessment/diagnosis of dementia; health economic evaluation using decision modeling. Ten databases were searched for 2000–2024. Philips checklist was applied for quality assessment. Narrative synthesis appraised methodological features and issued decision-making recommendations. Thirty-two studies were included. Six evaluated cerebrospinal fluid (CSF); 11 neuroimaging including amyloid-targeting positron emission tomography; three blood-based biomarkers; two genetic testing; and 10 early assessment/diagnosis strategies. Methodological limitations included non-consideration of capacity constraints. Decision-making recommendations generally affirmed current clinical guidelines: for example, CSF to confirm Alzheimer's disease is cost-effective (incremental cost-effectiveness ratio of £10,150 per quality-adjusted life-year gained vs. no use). Methodological appraisal and decision-making recommendations should assist model development and evidence-based dementia diagnosis.

Objective/purpose: This study reports on a case series of clients using individualized homeopathy on a wide variety of health complaints seen in cases from a supervised teaching clinical setting between 2017 and 2020 at the Academy of Homeopathy Education. This teaching clinic sees self-selecting clients of all ages, and cases were taken by faculty or advanced students and subsequently managed by advanced students under supervision. Methods: The cohort study evaluated n = 85 cases using the patient-generated outcome measure, the Measure Yourself Medical Outcome Profile (MYMOP). Average MYMOP values for initial and final consultations were analyzed for degree of change across the intervention period. Principle Results: Scores from initial consultation to last follow up showed a positive change in 80.23 % of cases. Clinically significant improvements were seen in all profile areas. The average profile score at last reported follow up of all cases showed a reduction in symptom severity of.56, and the greatest change between first and last average MYMOP scores showed a reduction of 1.2 after the homeopathic intervention. The greatest positive change was seen in Skin (1.88) followed by Respiratory (1.83) and Digestive-related (1.71) complaints. Conclusions: Clinically significant improvement in physical and psychological health is found across a diverse population of people with a wide variety of long-term conditions. These results suggest that individualized homeopathic care in a teaching clinic setting proved to be valuable for complex chronic health problems, and that further similar, confirmatory research is warranted.

BACKGROUND:UK cardiovascular disease (CVD) incidence and mortality have declined in recent decades but socioeconomic inequalities persist. AIM:To present a new CVD model, and project health outcomes and the impact of guideline-recommended statin treatment across quintiles of socioeconomic deprivation in the UK. DESIGN AND SETTING:A lifetime microsimulation model was developed using 117 896 participants in 16 statin trials, 501 854 UK Biobank (UKB) participants, and quality-of-life data from national health surveys. METHOD:A CVD microsimulation model was developed using risk equations for myocardial infarction, stroke, coronary revascularisation, cancer, and vascular and non-vascular death, estimated using trial data. The authors calibrated and further developed this model in the UKB cohort, including further characteristics and a diabetes risk equation, and validated the model in UKB and Whitehall II cohorts. The model was used to predict CVD incidence, life expectancy, quality-adjusted life years (QALYs), and the impact of UK guideline-recommended statin treatment across socioeconomic deprivation quintiles. RESULTS:Age, sex, socioeconomic deprivation, smoking, hypertension, diabetes, and cardiovascular events were key CVD risk determinants. Model-predicted event rates corresponded well to observed rates across participant categories. The model projected strong gradients in remaining life expectancy, with 4-5-year (5-8 QALYs) gaps between the least and most socioeconomically deprived quintiles. Guideline-recommended statin treatment was projected to increase QALYs, with larger gains in quintiles of higher deprivation. CONCLUSION:The study demonstrated the potential of guideline-recommended statin treatment to reduce socioeconomic inequalities. This CVD model is a novel resource for individualised long-term projections of health outcomes of CVD treatments.

AbstractBackgroundDifficulties identifying anxiety disorders in primary‐school aged children present significant barriers to timely access to support and intervention. This study aimed to develop a brief assessment tool that can identify children with anxiety disorders in community settings, with a high level of sensitivity and specificity.MethodsChildren (aged 8–11 years), and their parents/carers and teachers from 19 primary/junior schools in England each completed a pool of questionnaire items that assessed child anxiety symptoms and associated impact. Diagnostic assessments (Anxiety Disorder Interview Schedule for Children: Child and Parent interviews) were administered by independent assessors to determine the presence/absence of anxiety disorders in children. We created alternative candidate brief child‐, parent‐, teacher‐report questionnaires consisting of the ‘best’ items selected from the wider pool of completed items. We used exploratory factor analysis to reduce the item pool, and multivariable backward elimination logistic regression to identify items that were the strongest predictors of the presence/absence of an anxiety disorder.ResultsParents/carers of 646 children provided consent; child/parent/teacher‐report questionnaires were collected for 582/646/565 children respectively; and diagnostic outcome data were collected for 463 children. None of the brief child‐ nor teacher‐report questionnaires achieved acceptable sensitivity/specificity (<75%). Parent‐report questionnaires including between 2 and 9 items that assess anxiety symptoms and/or associated impact achieved acceptable sensitivity and specificity (≥75%).ConclusionsThe two‐item parent‐report measure that assesses distress and impairment associated with anxiety brings the advantage of brevity and has the potential to be used in community settings to improve identification of children with anxiety disorders.

AbstractAimsTransthyretin amyloid cardiomyopathy (ATTR‐CM) is an increasinglyrecognized cause of heart failure with preserved ejection fraction (HFpEF), which may be diagnosed non‐invasively using 99mTc 3,3‐diphosphono‐1,2‐propanodicarboxylic acid (DPD) scintigraphy‐based diagnostic criteria. Our aim was to determine the prevalence of ATTR‐CM in an undifferentiated HFpEF cohort with a DPD scintigraphy‐based screening protocol.MethodsPatients with HFpEF [ejection fraction (EF) ≥50%] aged ≥60 years and no prior evaluation for cardiac amyloidosis or known monoclonal gammopathy attending a regional cardiology network were screened with DPD scintigraphy. Patients with positive myocardial uptake (Perugini grade 2 or 3) were tested for a monoclonal protein and transthyretin gene variant.ResultsEighty‐six subjects were prospectively enrolled: 56% female, mean age 77 ± 8 years, 63% New York Heart Association (NYHA) Class III and median N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) 1766 ng/L [inter‐quartile range (IQR) 731–3703]. DPD scintigraphy was positive in seven patients (8%). Monoclonal gammopathy of undetermined significance was present in one out of seven patients, and no pathogenic TTR gene variant was identified. The prevalence of wild‐type ATTR‐CM was 8% of this cohort. Compared with the HFpEF DPD scintigraphy‐negative cohort, DPD scintigraphy‐positive patients were older (86 ± 3 vs. 76 ± 8 years), more frequently male (16% vs. 2%, P = 0.02), and had significantly greater left ventricular (LV) wall thickness (16 vs. 12 mm; P = 0.002) and higher high‐sensitivity troponin levels at diagnosis [78 ng/L (IQR 21–116) vs. 11 ng/L (IQR 9–17); P < 0.001].ConclusionsIn an undifferentiated HFpEF cohort, 8% were found to have wild‐type ATTR‐CM using a DPD scintigraphy‐based screening protocol. Screening undifferentiated HFpEF patients is associated with a significant diagnostic yield, which can be further increased by targeting older males with increased LV wall thickness and elevated high‐sensitivity troponin levels.

Abstract Background Comprehensive stroke centres across England have developed investment proposals, showing the estimated increases in mechanical thrombectomy (MT) treatment volume that would justify extending the standard hours to a 24/7 service provision. These investment proposals have been developed taking a financial accounting perspective, that is by considering the financial revenues from tariff income. However, given the pressure put on local health authorities to provide value for money services, an affordability question emerges. That is, at what additional MT treatment volume the additional treatment costs are offset by the additional health economic benefits, that is quality-adjusted life years (QALYs) and societal cost savings, generated by administering MT compared to standard care. Methods A break-even analysis was conducted to identify the additional MT treatment volume required. The incremental hospital-related costs associated with the 24/7 MT extension were estimated using information and parameters from four relevant business cases. The additional societal cost savings and health benefits were estimated by adapting a previously developed Markov chain-based model. Results The additional hospital-related annual costs for extending MT to a 24/7 service were estimated at a mean of £3,756,818 (range £1,847,387 to £5,092,788). On average, 750 (range 246 to 1,571) additional eligible stroke patients are required to be treated with MT yearly for the proposed 24/7 service extension to be affordable from a health economic perspective. Overall, the additional facility and equipment costs associated with the 24/7 extension would affect this estimate by 20%. Conclusions These findings support the ongoing debate regarding the optimal levels of MT treatment required for a 24/7 extension and respective changes in hospital organisational activities. They also highlight a need for a regional-level coordination between local authorities and hospital administrations to ensure equity provision in that stroke patients can benefit from MT and that the optimal MT treatment volume is reached. Future studies should contemplate reproducing the presented analysis for different health service provision settings and decision making contexts.

Background:Cardiovascular disease has declined but remains a major disease burden across developed countries. Objective:To assess the effectiveness and cost-effectiveness of statin therapy across United Kingdom population categories. Design:The cardiovascular disease microsimulation model, developed using Cholesterol Treatment Trialists' Collaboration data and the United Kingdom Biobank cohort, projected cardiovascular events, mortality, quality of life and healthcare costs using participant characteristics. Setting:United Kingdom primary health care. Participants:A total of 117,896 participants in 16 statin trials in the Cholesterol Treatment Trialists' Collaboration; 501,854 United Kingdom Biobank participants by previous cardiovascular disease status, sex, age (40-49, 50-59 and 60-70 years), 10-year cardiovascular disease risk [QRISK®3 (%): < 5, 5-10, 10-15, 15-20 and ≥ 20] and low-density lipoprotein cholesterol level (< 3.4, 3.4-4.1 and ≥ 4.1 mmol/l); 20,122 United Kingdom Biobank and Whitehall II participants aged ≥ 70 years by previous cardiovascular disease status, sex and low-density lipoprotein cholesterol (< 3.4, 3.4-4.1 and ≥ 4.1 mmol/l). Interventions:Lifetime standard (35-45% low-density lipoprotein cholesterol reduction) or higher-intensity (≥ 45% reduction) statin. Main outcome measures:Quality-adjusted life-years and incremental cost per quality-adjusted life-year gained from the United Kingdom healthcare perspective. Data sources:Cholesterol Treatment Trialists' Collaboration and United Kingdom Biobank data informed risk equations. United Kingdom primary and hospital care data informed healthcare costs (2020-1 Great British pounds); £1.10 standard or £1.68 higher-intensity generic statin therapy per 28 tablets; and Health Survey for England data informed health-related quality of life. Meta-analyses of trials and cohort studies informed the effects of statin therapies on cardiovascular events, incident diabetes, myopathy and rhabdomyolysis. Results:Across categories of participants 40-70 years old, lifetime use of standard statin therapy resulted in undiscounted 0.20-1.09 quality-adjusted life-years gained per person, and higher-intensity statin therapy added a further 0.03-0.20 quality-adjusted life-years per person. Among participants aged ≥ 70 years, lifetime standard statin was estimated to increase quality-adjusted life-years by 0.24-0.70 and higher-intensity statin by a further 0.04-0.13 quality-adjusted life-years per person. Benefits were larger among participants at higher cardiovascular disease risk or with higher low-density lipoprotein cholesterol. Standard statin therapy was cost-effective across all categories of people 40-70 years old, with incremental costs per quality-adjusted life-year gained from £280 to £8530. Higher-intensity statin therapy was cost-effective at higher cardiovascular disease risk or higher low-density lipoprotein cholesterol. Both standard and higher-intensity statin therapies appeared to be cost-effective for people aged ≥ 70 years, with an incremental cost per quality-adjusted life-year gained of under £3500 for standard and under £11,780 for higher-intensity statin. Standard or higher-intensity statin therapy was certain to be cost effective in the base-case analysis at a threshold of £20,000 per quality-adjusted life-year. Statins remained cost-effective in sensitivity analyses. Limitations:The randomised evidence for effects of statin therapy is for about 5 years of treatment. There is limited randomised evidence of the effects of statin therapy in older people without previous cardiovascular disease. Conclusions:Based on the current evidence of the effects of statin therapy and modelled contemporary disease risks, low-cost statin therapy is cost-effective across all categories of men and women aged ≥ 40 years in the United Kingdom, with higher-intensity statin therapy cost-effective at higher cardiovascular disease risk or higher low-density lipoprotein cholesterol. Future work:Cholesterol Treatment Trialists' Collaboration has ongoing studies of effects of statin therapy using individual participant data from randomised statin trials. Ongoing large randomised controlled trials are studying the effects of statin therapy in people ≥ 70 years old. Future economic analyses should integrate the emerging new evidence. Funding:This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/140/02) and is published in full in Health Technology Assessment; Vol. 28, No. 79. See the NIHR Funding and Awards website for further award information.

Objective Cardiovascular disease (CVD) is the leading cause of death across Europe. We estimated lost earnings (productivity losses) associated with premature mortality due to CVD, and separately for its main sub-categories of coronary heart disease and cerebrovascular disease, across 54 country members of the European Society of Cardiology (ESC). Methods and results We used a standardized approach to estimate working years and earnings lost due to premature death resulting from CVD across the 54 ESC member countries in 2018. Our population-based approach was based on national data on the number of deaths, employment rates, and earnings by age group and sex. We discounted future working years and earnings lost to present values using a 3.5% annual rate. In 2018, there were 4.4 million deaths due to CVD across the 54 countries, with 7.1 million working years lost. This represented productivity losses due to premature death of _62 billion in 2018. Deaths due to coronary heart disease accounted for 47% (_29 billion) of all CVD costs, and cerebrovascular disease accounted for 18% (_11 billion). Approximately 60% (_37 billion) of all productivity losses occurred in the 28 European Union member states, despite accounting for only 42% (1.8 million) of deaths and 21% (1.5 million) of working years lost across the 54 countries. Conclusion Our study provides a snapshot of the economic consequences posed by premature mortality due to CVD across 54 countries in 2018. The considerable variation across countries highlights the potential gains from policies targeting prevention and care of cardiovascular diseases. [GRAPHICS]

OBJECTIVES:This article identifies minimal clinically important differences (MCIDs) in quality of life (QoL) measures among patients who had coronary artery bypass grafting (CABG) and were enrolled in the arterial revascularization trial (ART). METHODS AND RESULTS:The European Quality of Life-5 Dimensions (EQ-5D) and the Short Form Health Survey 36-Item (SF-36) physical component (PC) and mental component (MC) scores were recorded at baseline, 5 years and 10 years in ART. The MCIDs were calculated as changes in QoL scores anchored to 1-class improvement in the New York Heart Association functional class and Canadian Cardiovascular Society scale at 5 years. Cox proportional hazard models were used to evaluate associations between MCIDs and mortality. Patient cohorts were examined for the SF-36 PC (N = 2671), SF-36 MC (N = 2815) and EQ-5D (N = 2943) measures, respectively. All QoL scores significantly improved after CABG compared to baseline. When anchored to the New York Heart Association, the MCID at 5 years was 17 (95% confidence interval: 17-20) for SF-36 PC, 14 (14-17) for the SF-36 MC and 0.12 (0.12-0.15) for EQ-5D. Using the Canadian Cardiovascular Society scale as an anchor, the MCID at 5 years was 15 (15-17) for the SF-36 PC, 12 (13-15) for the SF-36 MC and 0.12 (0.11-0.14) for the EQ-5D. The MCIDs for SF-36 PC and EQ-5D at 5 years were associated with a lower risk of mortality at the 10-year follow-up point after surgery. CONCLUSIONS:MCIDs for CABG patients have been identified. These thresholds may have direct clinical applications in monitoring patients during follow-up and in designing new trials that include QoL as a primary study outcome. CLINICAL TRIAL REGISTRATION NUMBER:ISRCTN46552265.

Background Cardiovascular disease incidence and mortality have declined across developed economies and granular up-to-date cost-effectiveness evidence is required for treatments targeting large populations. To assess the health bene fi ts and cost-effectiveness of standard and higher intensity statin therapy in the contemporary UK population 40 - 70 years old. Methods A cardiovascular disease microsimulation model, developed using the Cholesterol Treatment Trialists ' Collaboration data (117,896 participants; 5 years follow-up), and calibrated in the UK Biobank cohort (501,854 participants; 9 years follow-up), projected risks of myocardial infarction, stroke, coronary revascularization, diabetes, cancer and vascular and nonvascular death for all UK Biobank participants without and with statin treatment. Meta -analyses of trials and cohort studies informed statins ' relative effects on cardiovascular events, incident diabetes, myopathy and rhabdomyolysis. UK healthcare perspective was taken (2020/2021 UKL) with costs per 28 tablets of L1.10 for standard (35% - 45% LDL cholesterol (LDL-C) reduction) and L1.68 for higher intensity ( >= 45% LDL-C reduction) generic statin. Findings Across categories by sex, age, LDL-C, and cardiovascular disease history/10-year cardiovascular risk, lifetime standard statin increased survival by 0.28 - 1.85 years (0.20 - 1.09 quality -adjusted life years (QALYs)), and higher intensity statin by further 0.06 - 0.40 years (0.03 - 0.20 QALYs) per person. Standard statin was costeffective across all categories with incremental cost per QALY from L280 to L8530, with higher intensity statin cost-effective at higher cardiovascular risks and higher LDL-C levels. Stopping statin early reduced bene fi ts and was not cost-effective. Interpretation Lifetime low-cost statin therapy is cost-effective across all 40 - 70 years old in UK. Strengthening and widening statin treatment could cost-effectively improve population health. Funding UK NIHR Health Technology Assessment Programme (17/140/02). Copyright (c) 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Aims We examine the effects of symptoms and cardiovascular disease (CVD) events on health-related quality of life (HRQOL) and healthcare costs in a European population with atrial fibrillation (AF).Methods and results In the EURObservational Research Programme on AF long-term general registry, AF patients from 250 centres in 27 European countries were enrolled and followed for 2 years. We used fixed effects models to estimate the association of symptoms and CVD events on HRQOL and annual healthcare costs. We found significant decrements in HRQOL in AF patients in whom ST-segment elevation myocardial infarction (STEMI) [-0.075 (95% confidence interval -0.144, -0.006)], angina or non-ST-elevation myocardial infarction (NSTEMI) [-0.037 (-0.071, -0.003)], new-onset/worsening heart failure [-0.064 (-0.088, -0.039)], bleeding events [-0.031 (-0.059, -0.003)], thromboembolic events [-0.071 (-0.115, -0.027)], mild symptoms [0.037 (-0.048, -0.026)], or severe/disabling symptoms [-0.090 (-0.108, -0.072)] occurred during the follow-up. During follow-up, annual healthcare costs were associated with an increase of 11 718 (8497, 14 939) in patients with STEMI, 5823 (4757, 6889) in patients with angina/NSTEMI, 3689 (3219, 4158) in patients with new-onset or worsening heart failure, 3792 (3315, 4270) in patients with bleeding events, and 3182 (2483, 3881) in patients with thromboembolic events, compared with AF patients without these events. Healthcare costs were primarily driven by inpatient costs. There were no significant differences in HRQOL or healthcare resource use between EU regions or by sex.Conclusion Symptoms and CVD events are associated with a high burden on AF patients and healthcare systems throughout Europe. Graphical Abstract

BackgroundAntiplatelet therapy (APT) can substantially reduce the risk of further vascular events in individuals with established atherosclerotic cardiovascular disease (ASCVD). However, knowledge regarding the extent and determinants of APT use is limited.ObjectivesEstimate the extent and identify patient groups at risk of suboptimal APT use at different stages of the treatment pathway.MethodsRetrospective cohort study using linked NHS Scotland administrative data of all adults hospitalised for an acute ASCVD event (n=150 728) from 2009 to 2017. Proportions of patients initiating, adhering to, discontinuing and re-initiating APT were calculated overall and separately for myocardial infarction (MI), ischaemic stroke and peripheral arterial disease (PAD). Multivariable logistic regression and Cox proportional hazards models were used to assess the contribution of patient characteristics in initiating and discontinuing APT.ResultsOf patients hospitalised with ASCVD, 84% initiated APT: 94% following an MI, 83% following an ischaemic stroke and 68% following a PAD event. Characteristics associated with lower odds of initiation included female sex (22% less likely than men), age below 50 years or above 70 years (aged <50 years 26% less likely, and aged 70–79, 80–89 and ≥90 years 21%, 39% and 51% less likely, respectively, than those aged 60–69 years) and history of mental health-related hospitalisation (45% less likely). Of all APT-treated individuals, 22% discontinued treatment. Characteristics associated with discontinuation were similar to those related to non-initiation.ConclusionsAPT use remains suboptimal for the secondary prevention of ASCVD, particularly among women and older patients, and following ischaemic stroke and PAD hospitalisations.

BackgroundCardiovascular disease (CVD) risk increases with age. Statins reduce cardiovascular risk but their effects are less certain at older ages. We assessed the long-term effects and cost-effectiveness of statin therapy for older people in the contemporary UK population using a recent meta-analysis of randomised evidence of statin effects in older people and a new validated CVD model.MethodsThe performance of the CVD microsimulation model, developed using the Cholesterol Treatment Trialists’ Collaboration (CTTC) and UK Biobank cohort, was assessed among participants ≥70 years old at (re)surveys in UK Biobank and the Whitehall II studies. The model projected participants’ cardiovascular risks, survival, quality-adjusted life years (QALYs) and healthcare costs (2021 UK£) with and without lifetime standard (35%–45% low-density lipoprotein cholesterol reduction) or higher intensity (≥45% reduction) statin therapy. CTTC individual participant data and other meta-analyses informed statins’ effects on cardiovascular risks, incident diabetes, myopathy and rhabdomyolysis. Sensitivity of findings to smaller CVD risk reductions and to hypothetical further adverse effects with statins were assessed.ResultsIn categories of men and women ≥70 years old without (15,019) and with (5,103) prior CVD, lifetime use of a standard statin increased QALYs by 0.24–0.70 and a higher intensity statin by a further 0.04–0.13 QALYs per person. Statin therapies were cost-effective with an incremental cost per QALY gained below £3502/QALY for standard and below £11778/QALY for higher intensity therapy and with high probability of being cost-effective. In sensitivity analyses, statins remained cost-effective although with larger uncertainty in cost-effectiveness among older people without prior CVD.ConclusionsBased on current evidence for the effects of statin therapy and modelling analysis, statin therapy improved health outcomes cost-effectively for men and women ≥70 years old.

Diabetes and obesity are common conditions which can influence outcomes after coronary artery bypass graft (CABG) surgery. The aim of this study was to evaluate the influence of diabetes and obesity, and their interactions, on ten-year outcomes following CABG. Patients enrolled in the Arterial Revascularisation Trial (ART) were stratified by diabetes and obesity at baseline. Diabetes was further stratified into insulin and non-insulin dependent. The primary outcome was all-cause mortality at 10 years of follow-up. Secondary outcomes were the composite of all-cause mortality, myocardial infarction or stroke at 10 years, and sternal wound complications at 6 months follow-up. A total of 3096 patients were included in the analysis (24