卫生技术评估 (HTA) 为在 NHS 中使用、管理和提供护理的人发布有关卫生技术的有效性、成本和更广泛影响的研究信息。

The Health Technology Assessment journal publishes research information on the effectiveness, cost, and broader impacts of health technologies used, managed, and provided in the National Health Service (NHS), aiming to provide scientific evidence for professionals involved in care delivery.

卫生技术评估 (Health Technology Assessment) 期刊发布有关卫生技术在英国国家卫生服务体系 (NHS) 中的有效性、成本及其更广泛影响的研究信息，旨在为使用、管理和提供护理的专业人士提供科学依据。

Health Technology Assessment

Background Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow’s milk, prevents infections and associated complications. Objective To determine whether or not enteral supplementation with bovine lactoferrin (The Tatua Cooperative Dairy Company Ltd, Morrinsville, New Zealand) reduces the risk of late-onset infection (acquired &gt; 72 hours after birth) and other morbidity and mortality in very preterm infants. Design Randomised, placebo-controlled, parallel-group trial. Randomisation was via a web-based portal and used an algorithm that minimised for recruitment site, weeks of gestation, sex and single versus multiple births. Setting UK neonatal units between May 2014 and September 2017. Participants Infants born at &lt; 32 weeks’ gestation and aged &lt; 72 hours at trial enrolment. Interventions Eligible infants were allocated individually (1 : 1 ratio) to receive enteral bovine lactoferrin (150 mg/kg/day; maximum 300 mg/day) or sucrose (British Sugar, Peterborough, UK) placebo (same dose) once daily from trial entry until a postmenstrual age of 34 weeks. Parents, caregivers and outcome assessors were unaware of group assignment. Outcomes Primary outcome – microbiologically confirmed or clinically suspected late-onset infection. Secondary outcomes – microbiologically confirmed infection; all-cause mortality; severe necrotising enterocolitis (NEC); retinopathy of prematurity (ROP); bronchopulmonary dysplasia (BPD); a composite of infection, NEC, ROP, BPD and mortality; days of receipt of antimicrobials until 34 weeks’ postmenstrual age; length of stay in hospital; and length of stay in intensive care, high-dependency and special-care settings. Results Of 2203 enrolled infants, primary outcome data were available for 2182 infants (99%). In the intervention group, 316 out of 1093 (28.9%) infants acquired a late-onset infection versus 334 out of 1089 (30.7%) infants in the control group [adjusted risk ratio (RR) 0.95, 95% confidence interval (CI) 0.86 to 1.04]. There were no significant differences in any secondary outcomes: microbiologically confirmed infection (RR 1.05, 99% CI 0.87 to 1.26), mortality (RR 1.05, 99% CI 0.66 to 1.68), NEC (RR 1.13, 99% CI 0.68 to 1.89), ROP (RR 0.89, 99% CI 0.62 to 1.28), BPD (RR 1.01, 99% CI 0.90 to 1.13), or a composite of infection, NEC, ROP, BPD and mortality (RR 1.01, 99% CI 0.94 to 1.08). There were no differences in the number of days of receipt of antimicrobials, length of stay in hospital, or length of stay in intensive care, high-dependency or special-care settings. There were 16 reports of serious adverse events for infants in the lactoferrin group and 10 for infants in the sucrose group. Conclusions Enteral supplementation with bovine lactoferrin does not reduce the incidence of infection, mortality or other morbidity in very preterm infants. Future work Increase the precision of the estimates of effect on rarer secondary outcomes by combining the data in a meta-analysis with data from other trials. A mechanistic study is being conducted in a subgroup of trial participants to explore whether or not lactoferrin supplementation affects the intestinal microbiome and metabolite profile of very preterm infants. Trial registration Current Controlled Trials ISRCTN88261002. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 22, No. 74. See the NIHR Journals Library website for further project information. This trial was also sponsored by the University of Oxford, Oxford, UK. The funder provided advice and support and monitored study progress but did not have a role in study design or data collection, analysis and interpretation.

James Griffiths

Paula Jenkins

Monika Vargova

Ursula Bowler

Edmund Juszczak

Andrew King

Louise Linsell

David Murray

Christopher Partlett

Mehali Patel

Janet Berrington

Nicholas Embleton

Jon Dorling

Paul T Heath

William McGuire

Sam Oddie

Enteral lactoferrin to prevent infection for very preterm infants: the ELFIN RCT

肠乳铁蛋白预防极早产儿感染：ELFIN随机对照试验

Background NHS Stop Smoking Services (SSSs) provide free at the point of use treatment for smokers who would like to stop. Since their inception in 1999 they have evolved to offer a variety of support options. Given the changes that have happened in the provision of services and the ongoing need for evidence on effectiveness, the Evaluating Long-term Outcomes for NHS Stop Smoking Services (ELONS) study was commissioned. Objectives The main aim of the study was to explore the factors that determine longer-term abstinence from smoking following intervention by SSSs. There were also a number of additional objectives. Design The ELONS study was an observational study with two main stages: secondary analysis of routine data collected by SSSs and a prospective cohort study of service clients. The prospective study had additional elements on client satisfaction, well-being and longer-term nicotine replacement therapy (NRT) use. Setting The setting for the study was SSSs in England. For the secondary analysis, routine data from 49 services were obtained. For the prospective study and its added elements, nine services were involved. The target population was clients of these services. Participants There were 202,804 cases included in secondary analysis and 3075 in the prospective study. Interventions A combination of behavioural support and stop smoking medication delivered by SSS practitioners. Main outcome measures Abstinence from smoking at 4 and 52 weeks after setting a quit date, validated by a carbon monoxide (CO) breath test. Results Just over 4 in 10 smokers (41%) recruited to the prospective study were biochemically validated as abstinent from smoking at 4 weeks (which was broadly comparable with findings from the secondary analysis of routine service data, where self-reported 4-week quit rates were 48%, falling to 34% when biochemical validation had occurred). At the 1-year follow-up, 8% of prospective study clients were CO validated as abstinent from smoking. Clients who received specialist one-to-one behavioural support were twice as likely to have remained abstinent than those who were seen by a general practitioner (GP) practice and pharmacy providers [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.2 to 4.6]. Clients who received group behavioural support (either closed or rolling groups) were three times more likely to stop smoking than those who were seen by a GP practice or pharmacy providers (OR 3.4, 95% CI 1.7 to 6.7). Satisfaction with services was high and well-being at baseline was found to be a predictor of abstinence from smoking at longer-term follow-up. Continued use of NRT at 1 year was rare, but no evidence of harm from longer-term use was identified from the data collected. Conclusions Stop Smoking Services in England are effective in helping smokers to move away from tobacco use. Using the 52-week CO-validated quit rate of 8% found in this study, we estimate that in the year 2012–13 the services supported 36,249 clients to become non-smokers for the remainder of their lives. This is a substantial figure and provides one indicator of the ongoing value of the treatment that the services provide. The study raises a number of issues for future research including (1) examining the role of electronic cigarettes (e-cigarettes) in smoking cessation for service clients [this study did not look at e-cigarette use (except briefly in the longer-term NRT study) but this is a priority for future studies]; (2) more detailed comparisons of rolling groups with other forms of behavioural support; (3) further exploration of the role of practitioner knowledge, skills and use of effective behaviour change techniques in supporting service clients to stop smoking; (4) surveillance of the impact of structural and funding changes on the future development and sustainability of SSSs; and (5) more detailed analysis of well-being over time between those who successfully stop smoking and those who relapse. Further research on longer-term use of non-combustible nicotine products that measures a wider array of biomarkers of smoking-related harm such as lung function tests or carcinogen metabolites. Funding The National Institute for Health Research Health Technology Assessment programme. The UK Centre for Tobacco and Alcohol Studies provided funding for the longer-term NRT study.

Fiona Dobbie

Rosemary Hiscock

Jo Leonardi-Bee

Susan Murray

Lion Shahab

Paul Aveyard

Tim Coleman

Andy McEwen

Hayden McRobbie

Richard Purves

Linda Bauld

Evaluating Long-term Outcomes of NHS Stop Smoking Services (ELONS): a prospective cohort study

评估英国国民健康服务戒烟服务的长期结果（ELONS）：一项前瞻性队列研究

People with advanced dementia who live and die in nursing homes experience variable quality of life, care and dying. There is a need to identify appropriate, cost-effective interventions that facilitate high-quality end-of-life care provision.To establish the feasibility and acceptability to staff and family of conducting a cluster randomised controlled trial of the Namaste Care intervention for people with advanced dementia in nursing homes.The study had three phases: (1) realist review and (2) intervention refinement to inform the design of (3) a feasibility cluster randomised controlled trial with a process evaluation and economic analysis. Clusters (nursing homes) were randomised in a 3 : 1 ratio to intervention or control (usual care). The nature of the intervention meant that blinding was not possible.Nursing homes in England providing care for people with dementia.Residents with advanced dementia (assessed as having a Functional Assessment Staging Test score of 6 or 7), their informal carers and nursing home staff.Namaste Care is a complex group intervention that provides structured personalised care in a dedicated space, focusing on enhancements to the physical environment, comfort management and sensory engagement.The two contender primary outcome measures were Comfort Assessment in Dying - End of Life Care in Dementia for quality of dying (dementia) and Quality of Life in Late Stage Dementia for quality of life. The secondary outcomes were as follows: person with dementia, sleep/activity (actigraphy), neuropsychiatric symptoms, agitation and pain; informal carers, satisfaction with care at the end of life; staff members, person-centred care assessment, satisfaction with care at the end of life and readiness for change; and other data - health economic outcomes, medication/service use and intervention activity.Phase 1 (realist review; 86 papers) identified that a key intervention component was the activities enabling the development of moments of connection. In phase 2, refinement of the intervention enabled the production of a user-friendly 16-page A4 booklet. In phase 3, eight nursing homes were recruited. Two homes withdrew before the intervention commenced; four intervention and two control homes completed the study. Residents with advanced dementia (n = 32) were recruited in intervention (n = 18) and control (n = 14) homes. Informal carers (total, n = 12: intervention, n = 5; control, n = 7) and 97 staff from eight sites (intervention, n = 75; control, n = 22) were recruited over a 6-month period. Recruitment is feasible. Completion rates of the primary outcome questionnaires were high at baseline (100%) and at 4 weeks (96.8%). The Quality of Life in Late Stage Dementia was more responsive to change over 24 weeks. Even where economic data were missing, these could be collected in a full trial. The intervention was acceptable; the dose varied depending on the staffing and physical environment of each care home. Staff and informal carers reported changes for the person with dementia in two ways: increased social engagement and greater calm. No adverse events related to the intervention were reported.A subsequent definitive trial is feasible if there are amendments to the recruitment process, outcome measure choice and intervention specification.In a full trial, consideration is needed of the appropriate outcome measure that is sensitive to different participant responses, and of clear implementation principles for this person-centred intervention in a nursing home context.Current Controlled Trials ISRCTN14948133.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 6. See the NIHR Journals Library website for further project information.Namaste Care is a programme of respectful stimulation for nursing home residents who have advanced dementia. It is person-focused and reflects residents’ individual likes and interests. It is claimed that Namaste Care improves quality of life for residents, family and staff, and quality of dying for residents, and can be provided without additional cost. This study explored how feasible it would be to conduct a large study in the future to understand the effects of Namaste Care on people with advanced dementia. Our literature review showed that Namaste Care enables people with advanced dementia to have moments of connection with others. We refined some Namaste Care resources through working with care home staff, family and volunteers to create a user-friendly booklet. Eight care homes were recruited to our 6-month trial; four homes were supported to introduce Namaste Care, two continued as usual and two withdrew. In the four intervention homes, residents with advanced dementia received Namaste Care. Staff used standard measures to assess (1) residents’ responses and (2) the economic costs and benefits of Namaste Care. Researchers made observation visits. Records of activity in Namaste Care sessions were completed, and interviews were held with staff and family. Residents wore an ActiGraph (Activinsights Ltd, Kimbolton, UK) device that recorded their levels of sleep and activity. The length and frequency of Namaste Care sessions varied. Nursing homes incurred additional costs but could see ways to reduce those. All residents accepted wearing an ActiGraph device. Staff completed the data collection tools; some measures were more informative than others. Data from interviews showed that most people had positive experiences of Namaste Care. The findings support the view that Namaste Care has benefits for people with advanced dementia in nursing homes. We consider that, with some changes, this trial offers a model for a large study to show whether or not Namaste Care could be promoted more widely.

Katherine Froggatt

Ashley Best

Frances Bunn

Girvan Burnside

Joanna Coast

Lesley Dunleavy

Claire Goodman

Ben Hardwick

Clare Jackson

Julie Kinley

Anne Davidson Lund

Jennifer Lynch

Paul Mitchell

Gareth Myring

Shakil Patel

Guillermo Perez Algorta

Nancy Preston

David Scott

Kate Silvera

Catherine Walshe

A group intervention to improve quality of life for people with advanced dementia living in care homes: the Namaste feasibility cluster RCT

一项改善居住在护理院中的重度痴呆患者生活质量的团体干预：Namaste可行性集群随机对照试验

EOS is a biplane X-ray imaging system manufactured by EOS Imaging (formerly Biospace Med, Paris, France). It uses slot-scanning technology to produce a high-quality image with less irradiation than standard imaging techniques.To determine the clinical effectiveness and cost-effectiveness of EOS two-dimensional (2D)/three-dimensional (3D) X-ray imaging system for the evaluation and monitoring of scoliosis and other relevant orthopaedic conditions.For the systematic review of EOS, electronic databases (MEDLINE, Allied and Complementary Medicine Database, BIOSIS Previews, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library, EMBASE, Health Management Information Consortium, Inspec, ISI Science Citation Index and PASCAL), clinical trials registries and the manufacturer's website were searched from 1993 to November 2010.A systematic review of studies comparing EOS with standard X-ray [film, computed radiography (CR) or digital radiography] in any orthopaedic condition was performed. A narrative synthesis was undertaken. A decision-analytic model was developed to assess the cost-effectiveness of EOS in the relevant indications compared with standard X-ray and incorporated the clinical effectiveness of EOS and the adverse effects of radiation. The model incorporated a lifetime horizon to estimate outcomes in terms of quality-adjusted life-years (QALYs) and costs from the perspective of the NHS.Three studies met the inclusion criteria for the review. Two studies compared EOS with film X-ray and one study compared EOS with CR. The three included studies were small and of limited quality. One study used an earlier version of the technology, the Charpak system. Both studies comparing EOS with film X-ray found image quality to be comparable or better with EOS overall. Radiation dose was considerably lower with EOS: ratio of means for posteroanterior spine was 5.2 (13.1 for the study using the Charpak system); ratio of means for the lateral spine was 6.2 (15.1 for the study using the Charpak system). The study comparing EOS with CR found image quality to be comparable or better with EOS. Radiation dose was considerably lower with EOS than CR; ratio of means for the centre of the back was 5.9 and for the proximal lateral point 8.8. The lowest ratio of means was at the nape of the neck, which was 2.9. No other outcomes were assessed in the included studies, such as implications for patient management from the nature and quality of the image. Patient throughput is the major determinant of the cost-effectiveness of EOS. The average cost per procedure of EOS decreases with utilisation. Using estimates of patient throughput at national level from Hospital Episode Statistics data suggests that EOS is not cost-effective for the indications considered. Throughput in the region of 15,100 to 26,500 (corresponding to a workload of 60 to 106 patient appointments per working day) for EOS compared with a throughput of only 7530 for CR (30 patient appointments per working day) is needed to achieve an incremental cost-effectiveness ratio of £30,000 per QALY. EOS can be shown to be cost-effective only when compared with CR if the utilisation for EOS is about double the utilisation of CR.The main limitation of the systematic review of the clinical effectiveness of EOS was the limited number and quality of the data available. In particular, there were no studies assessing the potential health benefits arising from the quality and nature of the image, over and above those associated with reduced radiation exposure. Uncertainty in the model inputs was not fully explored owing to a lack of reporting of standard deviations or confidence intervals in the published literature for most of the parameters. As a result, uncertainty in the cost-effectiveness results was not presented.Radiation dose is considerably lower with EOS than standard X-ray, whereas image quality remains comparable or better with EOS. However, the long-term health benefits from reduced radiation exposure with EOS are very small and there was a lack of data on other potential patient health benefits. The implications of any changes in the quality and nature of the EOS image compared with standard X-ray, for patient health outcomes, needs to be assessed. Given the higher cost of an EOS machine, utilisation is the major determinant of cost-effectiveness. Estimates of patient throughput at national level suggest that EOS is not cost-effective.The National Institute for Health Research Health Technology Assessment programme.

C McKenna

R Wade

R Faria

H Yang

L Stirk

N Gummerson

M Sculpher

N Woolacott

EOS 2D/3D X-ray imaging system: a systematic review and economic evaluation

EOS 2D/3D X射线成像系统：系统综述与经济评估

Background Diabetic retinopathy is a major cause of sight loss in people with diabetes. The most severe form, proliferative diabetic retinopathy, carries a high risk of vision loss, vitreous haemorrhage, macular oedema and other harms. Panretinal photocoagulation is the primary treatment for proliferative diabetic retinopathy. Anti-vascular endothelial growth factor drugs are used to treat various eye conditions and may be beneficial for people with diabetic retinopathy. Objective To investigate the efficacy and safety of anti-vascular endothelial growth factor therapy for the treatment of diabetic retinopathy when compared to panretinal photocoagulation. Methods A systematic review and network meta-analysis of all published randomised controlled trials comparing anti-vascular endothelial growth factor (alone or in combination with panretinal photocoagulation) to panretinal photocoagulation in people with diabetic retinopathy. The database searches were updated in May 2023. Trials where the primary focus was treatment of macular oedema or vitreous haemorrhage were excluded. Results A total of 14 trials were included: 3 of aflibercept, 5 of bevacizumab and 6 of ranibizumab. Two trials were of patients with non-proliferative diabetic retinopathy; all others were in proliferative diabetic retinopathy. Overall, anti-vascular endothelial growth factor was slightly better than panretinal photocoagulation at preventing vision loss, measured as best corrected visual acuity, at up to 2 years follow-up [mean difference in the logarithm of the minimum angle of resolution −0.089 (or 3.6 Early Treatment Diabetic Retinopathy Study letters), 95% confidence interval −0.180 to −0.019]. There was no clear evidence of any difference between the anti-vascular endothelial growth factors, but the potential for bias complicated the comparison. One trial found no benefit of anti-vascular endothelial growth factor over panretinal photocoagulation after 5 years. Anti-vascular endothelial growth factor was superior to panretinal photocoagulation at preventing macular oedema (relative risk 0.29, 95% confidence interval 0.18 to 0.49) and vitreous haemorrhage (relative risk 0.77, 95% confidence interval 0.61 to 0.99). There was no clear evidence that the effectiveness of anti-vascular endothelial growth factor varied over time. Conclusions Anti-vascular endothelial growth factor injections reduce vision loss when compared to panretinal photocoagulation, but the benefit is small and unlikely to be clinically meaningful. Anti-vascular endothelial growth factor may have greater benefits for preventing complications such as macular oedema. Observational studies extending follow-up beyond the 1-year duration of most trials are needed to investigate the longer-term effects of repeated anti-vascular endothelial growth factor injections. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR132948.

Mark Simmonds

Alexis Llewellyn

Ruth Walker

Helen Fulbright

Matthew Walton

Rob Hodgson

Laura Bojke

Lesley Stewart

Sofia Dias

Thomas Rush

John G Lawrenson

Tunde Peto

David Steel

Anti-VEGF drugs compared with laser photocoagulation for the treatment of diabetic retinopathy: a systematic review and meta-analysis

抗VEGF药物与激光光凝治疗糖尿病视网膜病变的比较：一项系统评价和Meta分析

Background Hybrid closed-loop systems are a new class of technology to manage type 1 diabetes mellitus. The system includes a combination of real-time continuous glucose monitoring from a continuous glucose monitoring device and a control algorithm to direct insulin delivery through an insulin pump. Evidence suggests that such technologies have the potential to improve the lives of people with type 1 diabetes mellitus and their families. Aim The aim of this appraisal was to assess the clinical effectiveness and cost-effectiveness of hybrid closed-loop systems for managing glucose in people who have type 1 diabetes mellitus and are having difficulty managing their condition despite prior use of at least one of the following technologies: continuous subcutaneous insulin infusion, real-time continuous glucose monitoring or flash glucose monitoring (intermittently scanned continuous glucose monitoring). Methods A systematic review of clinical effectiveness and cost-effectiveness evidence following predefined inclusion criteria informed by the aim of this review. An independent economic assessment using iQVIA CDM to model cost-effectiveness. Results The clinical evidence identified 12 randomised controlled trials that compared hybrid closed loop with continuous subcutaneous insulin infusion + continuous glucose monitoring. Hybrid closed-loop arm of randomised controlled trials achieved improvement in glycated haemoglobin per cent [hybrid closed loop decreased glycated haemoglobin per cent by 0.28 (95% confidence interval −0.34 to −0.21), increased per cent of time in range (between 3.9 and 10.0 mmol/l) with a MD of 8.6 (95% confidence interval 7.03 to 10.22), and significantly decreased time in range (per cent above 10.0 mmol/l) with a MD of −7.2 (95% confidence interval −8.89 to −5.51), but did not significantly affect per cent of time below range (&lt; 3.9 mmol/l)]. Comparator arms showed improvements, but these were smaller than in the hybrid closed-loop arm. Outcomes were superior in the hybrid closed-loop arm compared with the comparator arm. The cost-effectiveness search identified six studies that were included in the systematic review. Studies reported subjective cost-effectiveness that was influenced by the willingness-to-pay thresholds. Economic evaluation showed that the published model validation papers suggest that an earlier version of the iQVIA CDM tended to overestimate the incidences of the complications of diabetes, this being particularly important for severe visual loss and end-stage renal disease. Overall survival’s medium-term modelling appeared good, but there was uncertainty about its longer-term modelling. Costs provided by the National Health Service Supply Chain suggest that hybrid closed loop is around an annual average of £1500 more expensive than continuous subcutaneous insulin infusion + continuous glucose monitoring, this being a pooled comparator of 90% continuous subcutaneous insulin infusion + intermittently scanned continuous glucose monitoring and 10% continuous subcutaneous insulin infusion + real-time continuous glucose monitoring due to clinical effectiveness estimates not being differentiated by continuous glucose monitoring type. This net cost may increase by around a further £500 for some systems. The Evidence Assessment Group base case applies the estimate of −0.29% glycated haemoglobin for hybrid closed loop relative to continuous subcutaneous insulin infusion + continuous glucose monitoring. There was no direct evidence of an effect on symptomatic or severe hypoglycaemia events, and therefore the Evidence Assessment Group does not include these in its base case. The change in glycated haemoglobin results in a gain in undiscounted life expectancy of 0.458 years and a gain of 0.160 quality-adjusted life-years. Net lifetime treatment costs are £31,185, with reduced complications leading to a net total cost of £28,628. The cost-effectiveness estimate is £179,000 per quality-adjusted life-year. Conclusions Randomised controlled trials of hybrid closed-loop interventions in comparison with continuous subcutaneous insulin infusion + continuous glucose monitoring achieved a statistically significant improvement in glycated haemoglobin per cent in time in range between 3.9 and 10 mmol/l, and in hyperglycaemic levels. Study registration This study is registered as PROSPERO CRD42021248512. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR133547) and is published in full in Health Technology Assessment ; Vol. 28, No. 80. See the NIHR Funding and Awards website for further award information.

Asra Asgharzadeh

Mubarak Patel

Martin Connock

Sara Damery

Iman Ghosh

Mary Jordan

Karoline Freeman

Anna Brown

Rachel Court

Sharin Baldwin

Fatai Ogunlayi

Chris Stinton

Ewen Cummins

Lena Al-Khudairy

Hybrid closed-loop systems for managing blood glucose levels in type 1 diabetes: a systematic review and economic modelling

1型糖尿病管理中的混合闭环系统：系统评价与经济模型

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 (%): &lt; 5, 5–10, 10–15, 15–20 and ≥ 20] and low-density lipoprotein cholesterol level (&lt; 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 (&lt; 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.

Borislava Mihaylova

Runguo Wu

Junwen Zhou

Claire Williams

Iryna Schlackow

Jonathan Emberson

Christina Reith

Anthony Keech

John Robson

Richard Parnell

Jane Armitage

Alastair Gray

John Simes

Colin Baigent

Assessing long-term effectiveness and cost-effectiveness of statin therapy in the UK: a modelling study using individual participant data sets

评估他汀类药物治疗在英国的长期疗效和成本效益：一项使用个体参与者数据集的建模研究

Background Urinary tract infections are diagnosed by general practitioners based on symptoms, dipstick tests in some and laboratory urine culture. Patients may be given inappropriate antibiotics. Point-of-care tests can diagnose urinary tract infection in near-patient settings quicker than standard culture. Some can identify the causative pathogen or antimicrobial sensitivity. Objective To assess whether point-of-care tests for people with suspected urinary tract infection have the potential to be clinically effective and cost-effective to the NHS. Design Systematic review and conceptual economic model. Results Two randomised controlled trials evaluated Flexicult Human (one against standard care; one against ID Flexicult). One trial found no evidence of a difference between groups in concordant antibiotic use (odds ratio 0.84, 95% confidence interval 0.58 to 1.20), and the other found no difference in appropriate antibiotic prescribing (odds ratio 1.44, 95% confidence interval 1.03 to 1.99). Compared with standard care, Flexicult was associated with reduced antibiotic prescribing at initial consultation (odds ratio 0.56, 95% confidence interval 0.35 to 0.88). No difference was found for other outcomes. Sixteen studies reported test accuracy data. Most were rated as being at unclear or high risk of bias. We identified data on three rapid tests (results &lt; 40 minutes). Lodestar DX ( n = 1) had good sensitivity (86%, 95% confidence interval 74% to 99%) and specificity (88%, 95% confidence interval 83% to 94%) for detecting Escherichia coli. Uriscreen ( n = 4) had modest summary sensitivity (74%, 95% confidence interval 59% to 84%) and specificity (64%, 95% confidence interval 41% to 82%). UTRiPLEX ( n = 1) had poor sensitivity (21%) and good specificity (94%). Twelve studies evaluated culture-based tests (results 24 hours). Laboratory-based studies found Dipstreak ( n = 2) and Uricult ( n = 1) to be highly accurate, but there were limitations with these studies. Uricult Trio ( n = 3) had more modest summary sensitivity (73%, 95% confidence interval 63% to 82%) and specificity (70%, 95% confidence interval 52% to 84%). Summary sensitivity for Flexicult Human ( n = 4) and ID Flexicult ( n = 2) was 79% (95% confidence interval 72% to 85%) and 89% (95% confidence interval 84% to 93%). Summary specificity was 67% (95% confidence interval 30% to 90%) and 70% (95% confidence interval 52% to 84%). Caution is needed in interpreting findings because of heterogeneity and limited data. Five studies evaluated technical performance (Flexicult Human, n = 3; Uricult Trio, n = 2). Limited data suggested that they are easier to use and interpret than standard culture. A conceptual economic model estimated the cost-effectiveness of point-of-care tests for urinary tract infection diagnosis, pathogen identification and antimicrobial sensitivity testing. Sensitivity and specificity of tests were informed by the clinical effectiveness review. Studies identified by the review were screened for evidence on treatment efficacy, costs and utility data; only two studies provided relevant evidence. A pragmatic search identified eight cost-effectiveness studies that provided further evidence. A decision tree comparing point-of-care tests in a mixed population (Lodestar DX vs. Flexicult Human) and in women with uncomplicated urinary tract infection (Lodestar DX vs. Flexicult Human vs. ID Flexicult) was implemented. The available input data were too limited for the results to be meaningful. Conclusion and future work More research is required to determine whether point-of-care tests for urinary tract infection have the potential to be clinically effective and cost-effective to the NHS. Rapid tests such as Astrego PA-100 system and Lodestar DX appear promising, but data are very limited. Study registration This study is registered as PROSPERO CRD42022383889. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR135710) and is published in full in Health Technology Assessment ; Vol. 28, No. 77. See the NIHR Funding and Awards website for further award information.

Eve Tomlinson

Mary Ward

Chris Cooper

Rachel James

Christina Stokes

Samina Begum

Jessica Watson

Alastair D Hay

Hayley E Jones

Howard Thom

Penny Whiting

Point-of-care tests for urinary tract infections to reduce antimicrobial resistance: a systematic review and conceptual economic model

用于减少抗生素耐药性的尿路感染即时检测：系统综述与概念性经济模型

Background Traumatic haemorrhage is common after severe injury, leading to disability and death. Cryoprecipitate, a source of fibrinogen, may improve outcomes for patients with traumatic haemorrhage. Objective To investigate the effects of early fibrinogen supplementation in the form of 3 pools (15 units, approximately 6 g of fibrinogen) of cryoprecipitate on 28-day mortality. Design A randomised, parallel-group, unblinded, multicentre, international trial and economic evaluation. Patients were randomised to either the intervention (early cryoprecipitate) or the comparator (standard major haemorrhage protocol) arm via opaque, sealed envelopes in the emergency department or the transfusion laboratory/blood bank. All analyses were performed on an intention-to-treat basis. A cost-effectiveness analysis was undertaken. Setting Twenty-five major trauma centres in the UK and one level 1 trauma centre in the USA. Participants Adults who had traumatic haemorrhage following severe injury requiring activation of the major haemorrhage protocol and had received a blood transfusion. Intervention Early cryoprecipitate – 3 pools (equivalent to 15 single units of cryoprecipitate or 6 g of fibrinogen supplementation), infused as rapidly as possible, within 90 minutes of arrival at hospital in addition to standard major haemorrhage protocol or standard major haemorrhage protocol only. Main outcome measures The primary outcome was all-cause mortality at 28 days. The secondary outcomes were all-cause mortality at 6 hours, 24 hours, 6 months and 12 months from admission; death from bleeding at 6 hours and 24 hours; transfusion requirements at 24 hours from admission; destination of participant at discharge; quality-of-life measurements (EuroQol-5 Dimensions, five-level version and Glasgow Outcome Scale) at discharge/day 28 and 6 months after injury; and hospital resource use up to discharge or day 28 (including ventilator-days, hours spent in critical care and inpatient stays). Results Eight hundred and five patients were randomised to receive the standard major haemorrhage protocol (control arm). Seven hundred and ninety-nine patients were randomised to receive an additional three pools of cryoprecipitate in addition to standard care (intervention arm). Baseline characteristics appeared well matched. Patients had a median age of 39 (interquartile range 26–55) years, and the majority (79%) were male. All-cause 28-day mortality ( n = 1531 patients; intention to treat) was 25.3% in the intervention arm compared with 26.1% in the control arm (odds ratio 0.96; p = 0.74). Limitations There was variability in the timing of cryoprecipitate administration, with overlap between the treatment arms, limiting the degree of intervention separation. Conclusions There was no evidence that early empiric administration of high-dose cryoprecipitate reduced the risk of death in unselected patients with traumatic haemorrhage. There was also no difference in adverse events. The cost-effectiveness of the intervention was similar to that of standard care. Future work Research to evaluate if fibrinogen replacement is more beneficial for selected patients, for example those with low fibrinogen blood levels, is needed, as is further exploration of whether there is a difference in outcome according to mechanism of injury. Trial registration This trial is registered as ISRCTN14998314. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/57/02) and is published in full in Health Technology Assessment ; Vol. 28, No. 76. See the NIHR Funding and Awards website for further award information.

Nicola Curry

Ross Davenport

Helen Thomas

Erin Fox

Joanne Lucas

Amy Evans

Efthalia Massou

Rupa Sharma

Shaminie Shanmugaranjan

Claire Rourke

Alice Newton

Alison Deary

Nikki Dallas

Chloe Fitzpatrick-Creamer

Jeanette M Podbielski

Charles E Wade

Antoinette Edwards

Jonathan Benger

Stephen Morris

Bryan A Cotton

James Piercy

Laura Green

Karim Brohi

Simon Stanworth

Early high-dose cryoprecipitate to reduce mortality in adult patients with traumatic haemorrhage: the CRYOSTAT-2 RCT with cost-effectiveness analysis

早期高剂量冷沉淀物减少创伤性出血成人患者死亡率：CRYOSTAT-2随机对照试验及成本效益分析

Abbreviation	Health Technol Assess
Journal Impact	3.62
Quartiles(Global)	HEALTH CARE SCIENCES & SERVICES(Q1)

ISSN	1366-5278, 2046-4924
h-index	141

Publication Information	Publisher: NIHR Journals Library，Publishing cycle: Irregular，Journal Type: journal，Open Access Journals: Yes
Basic data	Year of publication: 1994，Proportion of original research papers: 82.69%，Self Citation Rate:0.00%， Gold OA Rate: 96.91%
Average review cycle	网友分享经验：>12周，或约稿
Average recruitment ratio	网友分享经验：较难

Health Technology Assessment

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Assessing long-term effectiveness and cost-effectiveness of statin therapy in the UK: a modelling study using individual participant data sets

Point-of-care tests for urinary tract infections to reduce antimicrobial resistance: a systematic review and conceptual economic model

Early high-dose cryoprecipitate to reduce mortality in adult patients with traumatic haemorrhage: the CRYOSTAT-2 RCT with cost-effectiveness analysis