Alexander Thompson

Background: The economic burden of gonorrhoea extends beyond immediate treatment costs to include long-term sequelae, particularly in women. We estimated the economic burden for women, men who have sex with women (MSW), and men who have sex with men (MSM).Methods: We constructed sex-specific decision-analytic models capturing diagnostic pathways and sequelae. For women, we modelled pelvic inflammatory disease (PID), chronic pelvic pain, ectopic pregnancy, and tubal factor infertility. For men, we modelled epididymitis. We calculated lifetime costs and quality-adjusted life-year (QALY) losses.Findings: Probabilistic analysis showed mean total economic burden per infection was £1,769 (95% UI £1,085–2,835) for women, £201 (£180–225) for MSW, £269 (£233–314) for low-risk MSM, and £319 (£283–364) for high-risk MSM. Women experienced 0·076 QALYs lost per infection (95% UI 0·045–0·126), monetised as £1,529 at £20,000 per QALY, compared with 0·0034 (0·0026–0·0044) for MSW and 0·0057 (0·0039–0·0078) for MSM. In the deterministic base case, 89% of women’s QALY losses arose from chronic sequelae following PID. At the population level, 80,749 diagnoses across the United Kingdom in 2024 generated £47·51 million economic burden and 1,655 QALYs lost. In England, women were 20·7% of cases but had 79·6% of QALY losses. Sensitivity analysis showed a fixed 5-year chronic pelvic pain duration instead of lifetime to menopause reduced women’s burden by 37%.Interpretation: Lifetime burden per infection in women was about nine times that in MSW and about six times that in MSM due to reproductive sequelae. These findings support targeted prevention for asymptomatic infections in women.

Introduction: Distressing sensory experiences (DSEs) are commonly reported by children and young people accessing Child and Adolescent Mental Health Services (CAMHS) in the UK. Despite their prevalence, evidence-based tailored interventions for this population are scarce. The ChUSE trial aims to address this gap by evaluating the feasibility and acceptability of a novel brief talking therapy for children aged 8–16 years and an accompanying parent coaching programme. Methods and analysis: A single-blind, two-arm randomised controlled feasibility trial will be conducted across three National Health Service trusts in Greater Manchester, UK. Sixty young people under the care of CAMHS experiencing DSEs and their parents/caregivers will be randomised 1:1 to receive either treatment as usual (TAU) or TAU plus the ChUSE intervention. The intervention involves four child therapy sessions and three optional parent sessions. Primary feasibility outcomes include recruitment and retention rates, treatment adherence and intervention safety. Secondary objectives assess the feasibility of data collection procedures and gather qualitative insights into trial acceptability and the influence of the intervention on young people’s well-being. Ethics and dissemination: The ChUSE Trial has received ethical approval through the Health Research Authority following review by the West Midlands – South Birmingham Research Ethics Committee specialising in paediatric research (ID 327343). The feasibility trial addresses a significant clinical gap in CAMHS provision and will also capture information as to current TAU practices, contributing novel data to guide future service provision as TAU is currently understood to be heterogeneous. The information gathered through this trial will inform the design of a definitive trial evaluating the clinical effectiveness and cost-consequences of an early, age-appropriate intervention for DSEs. Findings and translational outputs will be shared through scientific and public forums to reach a variety of audiences. Trial registration number: ISRCTN12245618 .

Introduction: Although temporal variation is the hallmark of asthma, recommended diagnostic approaches largely rely on single clinic-based measurements. Ambulatory monitoring captures diurnal and day-to-day variability and may therefore enhance diagnostic accuracy. We evaluated the clinical feasibility and potential utility of home spirometry and fractional exhaled nitric oxide (FeNO) monitoring in asthma diagnosis. Methods: Symptomatic, untreated adults with GP-suspected asthma underwent diagnostic tests including bronchodilator reversibility, in-clinic FeNO, blood eosinophil counts and bronchial challenge. Participants measured spirometry and FeNO four times daily over one week; during the second week spirometry were measured twice daily. The reference standard was provided (asthma/not-asthma) by an expert panel of at least two asthma specialists based on clinical history and the results of all in-clinic testing; home spirometry (except for peak expiratory flow) and FeNO measurements were blinded to the panel. Results: Of 67 eligible participants, 51(76%) were recruited, and 38 had asthma confirmed or excluded by the panel. 1058 home spirometry measurements were obtained from 37(73%) participants; 848 home FeNO readings were obtained from 39(76%) participants. Among those completing at least one home measurement, median (IQR) adherence was 66.7(58.6-97.6)% for spirometry and 78.5(51.8-103.6)% for FeNO. Collection of health impact data for economic evaluation was feasible. In participants with a confirmed diagnostic outcome who completed home measurements (FeNO: n=32; spirometry: n=28), the putative home-testing metrics demonstrated high sensitivities at ≥90% specificity, and outperformed peak expiratory flow diurnal variability. Incorporating home testing into the BTS/NICE/SIGN 2024 diagnostic pathway had the potential to reduce reliance on bronchial challenge testing by 65%. Conclusions: Home spirometry and FeNO testing and the prospective collection of health-economic data in the diagnostic setting were feasible. Home-based testing strategy showed early potential to improve asthma diagnosis and pathway efficiency. These findings support further evaluation through an adequately powered diagnostic accuracy study and health-economic assessment. Key messages: What is already known on this topic: Asthma can be difficult to diagnose, as objective tests may be normal when assessments are performed during periods of minimal or intermittent symptoms. What this study adds: Our data suggest that home spirometry and FeNO monitoring could be successfully implemented within a diagnostic accuracy trial. Participants were able to perform these tests reliably in the home environment. How this study might affect research, practice or policy: The early findings suggest that home-based physiological monitoring may offer additive diagnostic value beyond standard clinic-based assessments and could reduce reliance on bronchial challenge testing. These results provide a clear rationale for larger diagnostic accuracy trials and for undertaking early health-economic modelling to assess the potential impact on clinical pathways and resource utilisation.

Background: Falls are the primary cause of fatal and nonfatal accidental injuries in older adults. The World Falls Prevention Guidelines recommend balance-challenging, functional exercise programs as a key strategy for falls prevention, but access, uptake, and adherence to these programs in community settings remain suboptimal. Keep-On-Keep-Up (KOKU), a digital, National Health Service–approved program, was codeveloped with older adults and therapists to provide progressive, evidence-based exercises and to raise awareness of falls prevention strategies. Objective: This trial aims to investigate the effectiveness and cost-effectiveness of the KOKU digital strength and balance program for improving balance, enhancing physical function, and reducing falls risk among community-dwelling older adults. Methods: This is a 2-arm, parallel-group randomized controlled trial. A total of 196 community-dwelling older adults 60 years and older will be randomized to either the intervention group, comprising a digital strength and balance program (KOKU) alongside standard care (strength and balance exercise advice and a falls prevention leaflet), or to a control group, receiving standard care only. Participants receiving the intervention will be asked to exercise 3 times per week following the tailored and progressive program. Randomization will take place after recruitment and baseline data collection. The trial’s primary outcome measure is balance function (Berg Balance Score) at 12 weeks post randomization. Secondary trial outcomes include lower limb strength, health care utilization and health-related quality of life, self-reported concerns about falling, self-reported physical activity, falls risk, pain, mood, fatigue, self-reported falls, and acceptability and usability of the KOKU program. Intention-to-treat analysis and a cost-effectiveness analysis will be employed for trial data analysis. Qualitative interviews and focus groups will be undertaken with around 10 care providers and 13 participants to further understand views of the intervention and trial processes. Results: This study began recruitment in July 2024 and concluded in March 2025, recruiting a total of 202 participants (102 intervention group and 100 control group). Following protocol publication, data compilation and analysis will be conducted, with results anticipated to be published in 2027. Conclusions: This trial will provide important evidence on whether a digital strength and balance program can improve balance and related outcomes in older adults compared with usual care.

The general impression from published economic evaluations is that the majority focus on quantifying the costs and benefits of ‘simple’ interventions. In practice, there are many examples of complex interventions. Indeed, by definition, all healthcare interventions are complex to some extent, but some can be viewed as being more ‘complex’ than others. Such different levels of complexity need to be acknowledged when applying methods of economic evaluation to inform the allocation of scarce healthcare resources. This chapter focuses on the underlying concepts that inform the economic evaluation framework, the different types of economic evaluation, key principles in the design and analysis methods for economic evaluations of complex interventions, together with key challenges for the design, conduct, and use of studies to evaluate the incremental costs and benefits of complex interventions in practice.

Objective: To evaluate the diagnostic accuracy of a novel point of care (POC) high‐sensitivity troponin (hs‐cTn) assay, used alone or incorporated within validated decision aids, for acute myocardial infarction (AMI) in the prehospital setting. Methods: A pre‐specified secondary analysis of the Prehospital Evaluation of Sensitive Troponin (PRESTO) prospective diagnostic accuracy study, conducted in four ambulance services and 12 Emergency Departments (EDs; February 2019–March 2020). Paramedics included consenting adults with suspected AMI and no other reason for conveyance. Clinical data and venous blood were collected at the scene, and samples conveyed to hospital with participants. Plasma samples were later analyzed for hs‐cTn using a novel POC hs‐cTn assay (Abbott Point of Care i‐STAT hs‐TnI). The target condition was an adjudicated index diagnosis of type 1 AMI. Results: Of 817 consenting participants, 704 were eligible for inclusion in this analysis, with type 1 AMI occurring in 89 (12.6%). At the limit of detection (< 2 ng/L), POC hs‐cTn had 100.0% sensitivity (95% CI 95 9%–100.0%) but only 4.6% specificity (95% CI 3.1%–6.5%). A Troponin‐only Manchester Acute Coronary Syndromes (T‐MACS) very‐low risk outcome identified 134 (19.7%) patients for non‐conveyance with 98.9% sensitivity (95% CI 94.9%–100.0%), 99.3% negative predictive value (NPV, 95% CI 95.0%–99.9%), and 22.5% specificity (95% CI 19.2%–26.1%). A low‐risk modified HEART score identified 150 (22.0%) patients with 93.2% sensitivity (95% CI 85.8%–97.5%), 96.0% NPV (91.6%–98.1%), and 24.3% specificity (95% CI 20.9%–27.9%). In an exploratory analysis, hs‐cTn < 5 ng/L identified 295 (41.9%) patients with 98.9% sensitivity (93.9%–100.0%), 99.7% NPV (97.7%–100.0%), and 47.8% specificity (95% CI 43.8%–51.8%). Conclusions: This novel POC hs‐cTn assay achieves high sensitivity and NPV when used alongside the T‐MACS decision aid, but efficiency may be greater at a 5 ng/L threshold without requiring any decision aid. Trial Registration: ClinicalTrials.gov identifier: NCT03561051

Background: Clinical guidelines commonly recommend preventative treatments for people above a risk threshold. Therefore, decision-makers must have faith in risk prediction tools and model-based cost-effectiveness analyses for people at different levels of risk. Two problems that arise are inadequate handling of competing risks of death and failing to account for direct treatment disutility (i.e. the hassle of taking treatments). We explored these issues using two case studies: primary prevention of cardiovascular disease using statins and osteoporotic fracture using bisphosphonates. Objectives: Externally validate three risk prediction tools [QRISK®3, QRISK®-Lifetime, QFracture-2012 (ClinRisk Ltd, Leeds, UK)]; derive and internally validate new risk prediction tools for cardiovascular disease [competing mortality risk model with Charlson Comorbidity Index (CRISK-CCI)] and fracture (CFracture), accounting for competing-cause death; quantify direct treatment disutility for statins and bisphosphonates; and examine the effect of competing risks and direct treatment disutility on the cost-effectiveness of preventative treatments. Design, participants, main outcome measures, data sources: Discrimination and calibration of risk prediction models (Clinical Practice Research Datalink participants: aged 25–84 years for cardiovascular disease and aged 30–99 years for fractures); direct treatment disutility was elicited in online stated-preference surveys (people with/people without experience of statins/bisphosphonates); costs and quality-adjusted life-years were determined from decision-analytic modelling (updated models used in National Institute for Health and Care Excellence decision-making). Results: CRISK-CCI has excellent discrimination, similar to that of QRISK3 (Harrell’s c = 0.864 vs. 0.865, respectively, for women; and 0.819 vs. 0.834, respectively, for men). CRISK-CCI has systematically better calibration, although both models overpredict in high-risk subgroups. People recommended for treatment (10-year risk of ≥ 10%) are younger when using QRISK-Lifetime than when using QRISK3, and have fewer observed events in a 10-year follow-up (4.0% vs. 11.9%, respectively, for women; and 4.3% vs. 10.8%, respectively, for men). QFracture-2012 underpredicts fractures, owing to under-ascertainment of events in its derivation. However, there is major overprediction among people aged 85–99 years and/or with multiple long-term conditions. CFracture is better calibrated, although it also overpredicts among older people. In a time trade-off exercise (n = 879), statins exhibited direct treatment disutility of 0.034; for bisphosphonates, it was greater, at 0.067. Inconvenience also influenced preferences in best–worst scaling (n = 631). Updated cost-effectiveness analysis generates more quality-adjusted life-years among people with below-average cardiovascular risk and fewer among people with above-average risk. If people experience disutility when taking statins, the cardiovascular risk threshold at which benefits outweigh harms rises with age (≥ 8% 10-year risk at 40 years of age; ≥ 38% 10-year risk at 80 years of age). Assuming that everyone experiences population-average direct treatment disutility with oral bisphosphonates, treatment is net harmful at all levels of risk. Limitations: Treating data as missing at random is a strong assumption in risk prediction model derivation. Disentangling the effect of statins from secular trends in cardiovascular disease in the previous two decades is challenging. Validating lifetime risk prediction is impossible without using very historical data. Respondents to our stated-preference survey may not be representative of the population. There is no consensus on which direct treatment disutilities should be used for cost-effectiveness analyses. Not all the inputs to the cost-effectiveness models could be updated. Conclusions: Ignoring competing mortality in risk prediction overestimates the risk of cardiovascular events and fracture, especially among older people and those with multimorbidity. Adjustment for competing risk does not meaningfully alter cost-effectiveness of these preventative interventions, but direct treatment disutility is measurable and has the potential to alter the balance of benefits and harms. We argue that this is best addressed in individual-level shared decision-making. Study registration: This study is registered as PROSPERO CRD42021249959. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 15/12/22) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 4. See the NIHR Funding and Awards website for further award information.

Background: School-based universal social and emotional learning (SEL) interventions implemented during the transition to adolescence may be efficacious in preventing the development of mental health difficulties. This protocol describes a two-arm parallel cluster randomised controlled trial to investigate the impact of a universal SEL intervention (Passport, compared to usual provision) on internalising symptoms (primary outcome), emotion regulation, well-being, loneliness, social support, bullying, academic attainment, and health-related quality of life in English primary school pupils aged 9–11 years. A developer-led trial demonstrated the feasibility, acceptability, and utility of Passport; this will be the first independent trial. Methods: Sixty primary schools will be recruited across the Greater Manchester city region and surrounding areas, involving 2400 pupils aged 8–9 at baseline. Schools will be allocated to the intervention arm to implement Passport over 18 weekly sessions or to the control arm to implement the usual school curriculum. Random allocation will be at school level following completion of baseline measures, with minimisation to ensure balance across trial arms in school size and free school meal eligibility. Measures will be collected at baseline, post-intervention (12 months post-baseline), and at 12 months follow-up (24 months post-baseline). The primary outcome analysis (intervention effects on internalising symptoms at post-intervention) will comprise a two-level (school, child) hierarchical linear model, following the intention-to-treat principle. Additional analyses will be undertaken to assess intervention effects on secondary outcomes, maintenance effects for all outcomes, intervention compliance moderator effects, subgroup moderator effects, and mechanisms underpinning intervention effects on the primary outcome. A mixed-methods implementation and process evaluation will examine factors that influence implementation, and a health economic evaluation will assess the cost-effectiveness of the intervention. Discussion: Findings will provide educators with crucial knowledge of whether and how increasing emotion regulation through a universal intervention impacts internalising symptoms and a range of related outcomes. Findings will also inform policy related to the promotion of mental health among children and young people. If the intervention is found to be efficacious in reducing internalising symptoms and is also cost-effective, it may offer high potential as a preventative intervention for widespread implementation. Trial registration: ISRCTN12875599; registered on 24 November 2022