Sofia Cividini, Ian Sinha, Giovanna Culeddu, Sarah Donegan, Michelle Maden, Katie Rose, Olivia Fulton, Dyfrig Hughes, Stephen Turner, Catrin Tudur Smith
<p><strong>Background: </strong>There is no clear preferential option for initial step-up of treatment for children with uncontrolled asthma on inhaled corticosteroid.</p><p><strong>Objectives: </strong>Evaluate the clinical effectiveness of pharmacological treatments to use in children with uncontrolled asthma on inhaled corticosteroid; identify and evaluate the potential for treatment effect modification to optimise treatment delivery; assess the cost-effectiveness of treatments.</p><p><strong>Methods: </strong>Systematic review and individual participant data network meta-analysis. Studies were eligible if they were parallel or crossover randomised controlled trials comparing at least one of the pharmacological treatments of interest in participants aged < 18 years with uncontrolled asthma on any dose inhaled corticosteroid alone. We searched MEDLINE<sup>®</sup>, Cochrane Library, Cochrane Central Register of Controlled Trials, EMBASE, National Institute for Health and Care Excellence Technology Appraisals, and the National Institute for Health and Care Research Health Technology Assessment series. Primary outcomes: exacerbation and asthma control. Secondary outcomes: health-related quality of life, mortality, forced expiratory volume in 1 second, adverse events, hospital admissions, symptoms (not analysed). We assessed the Risk Of Bias using the Cochrane Risk Of Bias tool and carried out Bayesian meta-analyses, network meta-analysis and network meta-regression, including treatment by covariate (age, sex, ethnicity, eczema, eosinophilia, asthma severity) interactions. A Markov decision-analytic model with a 12-month time horizon, which adopted the perspective of the National Health Service and Personal Social Services in the United Kingdom, was developed to compare alternative treatments. Cost-effectiveness was based on incremental costs per quality-adjusted life-years gained, with uncertainty considered in one-way, structural and probabilistic sensitivity analyses.</p><p><strong>Results: </strong>We identified and screened 4708 publications from the search and confirmed 144 randomised controlled trials as eligible. We obtained individual participant data from 29 trials (5381 participants) and extracted limited aggregate data from a further 19 trials. The majority of trials had low risk of bias. The network meta-analysis suggests that medium-dose inhaled corticosteroid + long-acting <i>β</i><sub>2</sub>-agonist is the preferred treatment for reducing odds of exacerbation [odds ratio 95% credibility interval: 0.43 (0.20 to 0.92) vs. low-dose inhaled corticosteroid; 40 studies, 8168 patients] and increasing forced expiratory volume in 1 second [mean difference 95% credibility interval: 0.71 (0.35 to 1.06) vs. low-dose inhaled corticosteroid; 23 studies, 2518 patients] while leukotriene receptor antagonist alone is the least preferred. No clear differences were found for asthma control (16 studies, 3027 patients). Limited pairwise analyses sugges
{"title":"Establishing the best step-up treatments for children with uncontrolled asthma despite inhaled corticosteroids: the EINSTEIN systematic review, network meta-analysis and cost-effectiveness analysis using individual participant data.","authors":"Sofia Cividini, Ian Sinha, Giovanna Culeddu, Sarah Donegan, Michelle Maden, Katie Rose, Olivia Fulton, Dyfrig Hughes, Stephen Turner, Catrin Tudur Smith","doi":"10.3310/HGWT3617","DOIUrl":"10.3310/HGWT3617","url":null,"abstract":"<p><strong>Background: </strong>There is no clear preferential option for initial step-up of treatment for children with uncontrolled asthma on inhaled corticosteroid.</p><p><strong>Objectives: </strong>Evaluate the clinical effectiveness of pharmacological treatments to use in children with uncontrolled asthma on inhaled corticosteroid; identify and evaluate the potential for treatment effect modification to optimise treatment delivery; assess the cost-effectiveness of treatments.</p><p><strong>Methods: </strong>Systematic review and individual participant data network meta-analysis. Studies were eligible if they were parallel or crossover randomised controlled trials comparing at least one of the pharmacological treatments of interest in participants aged < 18 years with uncontrolled asthma on any dose inhaled corticosteroid alone. We searched MEDLINE<sup>®</sup>, Cochrane Library, Cochrane Central Register of Controlled Trials, EMBASE, National Institute for Health and Care Excellence Technology Appraisals, and the National Institute for Health and Care Research Health Technology Assessment series. Primary outcomes: exacerbation and asthma control. Secondary outcomes: health-related quality of life, mortality, forced expiratory volume in 1 second, adverse events, hospital admissions, symptoms (not analysed). We assessed the Risk Of Bias using the Cochrane Risk Of Bias tool and carried out Bayesian meta-analyses, network meta-analysis and network meta-regression, including treatment by covariate (age, sex, ethnicity, eczema, eosinophilia, asthma severity) interactions. A Markov decision-analytic model with a 12-month time horizon, which adopted the perspective of the National Health Service and Personal Social Services in the United Kingdom, was developed to compare alternative treatments. Cost-effectiveness was based on incremental costs per quality-adjusted life-years gained, with uncertainty considered in one-way, structural and probabilistic sensitivity analyses.</p><p><strong>Results: </strong>We identified and screened 4708 publications from the search and confirmed 144 randomised controlled trials as eligible. We obtained individual participant data from 29 trials (5381 participants) and extracted limited aggregate data from a further 19 trials. The majority of trials had low risk of bias. The network meta-analysis suggests that medium-dose inhaled corticosteroid + long-acting <i>β</i><sub>2</sub>-agonist is the preferred treatment for reducing odds of exacerbation [odds ratio 95% credibility interval: 0.43 (0.20 to 0.92) vs. low-dose inhaled corticosteroid; 40 studies, 8168 patients] and increasing forced expiratory volume in 1 second [mean difference 95% credibility interval: 0.71 (0.35 to 1.06) vs. low-dose inhaled corticosteroid; 23 studies, 2518 patients] while leukotriene receptor antagonist alone is the least preferred. No clear differences were found for asthma control (16 studies, 3027 patients). Limited pairwise analyses sugges","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 15","pages":"1-234"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Steven J Edwards, Benjamin G Farrar, Kate Ennis, Nicole Downes, Victoria Wakefield, Isaac Mackenzie, Archie Walters, Tracey Jhita
<p><strong>Background: </strong>Cystic fibrosis is a life-limiting genetic condition that affects over 9000 people in England. Cystic fibrosis is usually diagnosed through newborn screening and causes symptoms throughout the body, including the lungs and digestive system. Around 90% of individuals with cystic fibrosis have at least one copy of the <i>F508del</i> mutation on the cystic fibrosis transmembrane conductance regulator gene.</p><p><strong>Objectives: </strong>To appraise the clinical effectiveness and cost-effectiveness of elexacaftor-tezacaftor-ivacaftor, tezacaftor-ivacaftor and lumacaftor-ivacaftor within their expected marketing authorisations for treating people with cystic fibrosis and at least one <i>F508del</i> mutation, compared with each other and with established clinical management before these treatments.</p><p><strong>Methods: </strong>A de novo systematic literature review (search date February 2023) was conducted searching electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials), bibliographies of relevant systematic literature reviews, clinical trial registers, recent conferences and evidence provided by Vertex Pharmaceuticals (Boston, MA, USA). Data on the following outcomes were summarised: acute change in per cent predicted forced expiratory volume in 1 second (change in weight-for-age <i>z</i>-score; and change in pulmonary exacerbation frequency requiring intravenous antibiotics. Network meta-analyses were conducted where head-to-head data were not available. Data from clinical trials and real-world evidence were examined to assess long-term effectiveness. A patient-level simulation model was developed to assess the cost-effectiveness of the three modulator treatments. The model employed a lifetime horizon and was developed from the perspective of the National Health Service.</p><p><strong>Results: </strong>Data from 19 primary studies and 7 open-label extension studies were prioritised in the systematic literature review. Elexacaftor/tezacaftor/ivacaftor was associated with a statistically significant increase in predicted forced expiratory volume in 1 second and weight-for-age <i>z</i>-score and a reduction in pulmonary exacerbations compared with established clinical management, lumacaftor/ivacaftor and tezacaftor/ivacaftor, and also led to a reduction in the rate of predicted forced expiratory volume in 1 second decline relative to established clinical management, although the magnitude of this decrease was uncertain. Lumacaftor/ivacaftor and tezacaftor/ivacaftor were also associated with a statistically significant increase in predicted forced expiratory volume in 1 second and reduction in pulmonary exacerbations relative to established clinical management, but with a smaller effect size than elexacaftor/tezacaftor/ivacaftor. There was some evidence that tezacaftor/ivacaftor reduced the rate of predicted forced expiratory volume in 1 second decline relative to established clinical
{"title":"Ivacaftor-tezacaftor-elexacaftor, tezacaftor-ivacaftor and lumacaftor-ivacaftor for treating cystic fibrosis: a systematic review and economic evaluation.","authors":"Steven J Edwards, Benjamin G Farrar, Kate Ennis, Nicole Downes, Victoria Wakefield, Isaac Mackenzie, Archie Walters, Tracey Jhita","doi":"10.3310/CPLD8546","DOIUrl":"10.3310/CPLD8546","url":null,"abstract":"<p><strong>Background: </strong>Cystic fibrosis is a life-limiting genetic condition that affects over 9000 people in England. Cystic fibrosis is usually diagnosed through newborn screening and causes symptoms throughout the body, including the lungs and digestive system. Around 90% of individuals with cystic fibrosis have at least one copy of the <i>F508del</i> mutation on the cystic fibrosis transmembrane conductance regulator gene.</p><p><strong>Objectives: </strong>To appraise the clinical effectiveness and cost-effectiveness of elexacaftor-tezacaftor-ivacaftor, tezacaftor-ivacaftor and lumacaftor-ivacaftor within their expected marketing authorisations for treating people with cystic fibrosis and at least one <i>F508del</i> mutation, compared with each other and with established clinical management before these treatments.</p><p><strong>Methods: </strong>A de novo systematic literature review (search date February 2023) was conducted searching electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials), bibliographies of relevant systematic literature reviews, clinical trial registers, recent conferences and evidence provided by Vertex Pharmaceuticals (Boston, MA, USA). Data on the following outcomes were summarised: acute change in per cent predicted forced expiratory volume in 1 second (change in weight-for-age <i>z</i>-score; and change in pulmonary exacerbation frequency requiring intravenous antibiotics. Network meta-analyses were conducted where head-to-head data were not available. Data from clinical trials and real-world evidence were examined to assess long-term effectiveness. A patient-level simulation model was developed to assess the cost-effectiveness of the three modulator treatments. The model employed a lifetime horizon and was developed from the perspective of the National Health Service.</p><p><strong>Results: </strong>Data from 19 primary studies and 7 open-label extension studies were prioritised in the systematic literature review. Elexacaftor/tezacaftor/ivacaftor was associated with a statistically significant increase in predicted forced expiratory volume in 1 second and weight-for-age <i>z</i>-score and a reduction in pulmonary exacerbations compared with established clinical management, lumacaftor/ivacaftor and tezacaftor/ivacaftor, and also led to a reduction in the rate of predicted forced expiratory volume in 1 second decline relative to established clinical management, although the magnitude of this decrease was uncertain. Lumacaftor/ivacaftor and tezacaftor/ivacaftor were also associated with a statistically significant increase in predicted forced expiratory volume in 1 second and reduction in pulmonary exacerbations relative to established clinical management, but with a smaller effect size than elexacaftor/tezacaftor/ivacaftor. There was some evidence that tezacaftor/ivacaftor reduced the rate of predicted forced expiratory volume in 1 second decline relative to established clinical","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 19","pages":"1-111"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ukachukwu O Abaraogu, Philippa Dall, Chris Seenan, Sarah Rhodes, Trish Gorely, Joanna McParland, Julie Brittenden, Ebuka M Anieto, Lorna Booth, Cathy Gormal, Jeremy Dearling, Candida Fenton, Sarah Audsley, Kimberley Fairer, Lindsay Bearne, Dawn A Skelton
Background: People with intermittent claudication are significantly less active compared to their peers without intermittent claudication, worsening future health outcomes. Supervised exercise therapy is not commonly available, but behaviour change techniques in unsupervised interventions can improve physical activity. Specific behaviour change techniques, theoretical mechanisms and contextual features linked to effectiveness remain unclear.
Objectives: To conduct an integrative synthesis of: effectiveness of behaviour change technique-based interventions on daily physical activity and clinical-/patient-reported outcomes; behaviour change techniques and theoretical mechanisms within effective behaviour change technique-based interventions; feasibility and acceptability. Primary outcomes: short term (< 6 months) and maintenance (> 6 months) of daily physical activity. Secondary outcomes: clinical-/patient-reported outcomes.
Data sources: Seven primary studies databases; Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, Health Technology Assessment Database and Trial Registers to 31 August 2023.
Review methods: Systematic review 1: interventions incorporating ≥ 1 behaviour change technique (coded using Behaviour Change Technique Taxonomy version 1, and Theoretical Domains Framework). Systematic review 2: quantitative, qualitative, mixed-methods research on patient/provider experiences. Study quality assessed using revised Cochrane risk-of-bias tool for randomised trials; Risk Of Bias In Non-randomised Studies - of Interventions and Mixed Methods Appraisal Tool.
Results: Fifty-three articles (41 studies) were included in systematic review 1, and 28 articles (28 studies) in systematic review 2. Eleven randomised controlled trials demonstrated that behaviour change technique-based interventions increased daily physical activity in the short term [increase of 0.20 standardised mean difference (95% confidence interval 0.07 to 0.33), ~ 473 steps/day] with high certainty. Evidence of maintenance of daily physical activity is unclear (increase of 0.12 standardised mean difference; ~ 288 steps/day). Behaviour change techniques aimed at improving patients' intentions to engage in physical activity were most effective. Network analysis suggests that behaviour change technique-based interventions improved daily physical activity and may be better than supervised exercise therapy in maintaining daily physical activity. behaviour change technique-based interventions were acceptable and had short-medium-term benefits to initial/absolute claudication distance/time, walking impairment scores and disease-specific quality of life.
Conclusions: The behaviour change technique-based interventions are effective, targeting intention to engage in physical activity, in improving daily physical activity
{"title":"Behaviour change interventions to promote physical activity in people with intermittent claudication: the OPTIMA systematic review.","authors":"Ukachukwu O Abaraogu, Philippa Dall, Chris Seenan, Sarah Rhodes, Trish Gorely, Joanna McParland, Julie Brittenden, Ebuka M Anieto, Lorna Booth, Cathy Gormal, Jeremy Dearling, Candida Fenton, Sarah Audsley, Kimberley Fairer, Lindsay Bearne, Dawn A Skelton","doi":"10.3310/ZBNG5240","DOIUrl":"10.3310/ZBNG5240","url":null,"abstract":"<p><strong>Background: </strong>People with intermittent claudication are significantly less active compared to their peers without intermittent claudication, worsening future health outcomes. Supervised exercise therapy is not commonly available, but behaviour change techniques in unsupervised interventions can improve physical activity. Specific behaviour change techniques, theoretical mechanisms and contextual features linked to effectiveness remain unclear.</p><p><strong>Objectives: </strong>To conduct an integrative synthesis of: effectiveness of behaviour change technique-based interventions on daily physical activity and clinical-/patient-reported outcomes; behaviour change techniques and theoretical mechanisms within effective behaviour change technique-based interventions; feasibility and acceptability. Primary outcomes: short term (< 6 months) and maintenance (> 6 months) of daily physical activity. Secondary outcomes: clinical-/patient-reported outcomes.</p><p><strong>Data sources: </strong>Seven primary studies databases; Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, Health Technology Assessment Database and Trial Registers to 31 August 2023.</p><p><strong>Review methods: </strong>Systematic review 1: interventions incorporating ≥ 1 behaviour change technique (coded using Behaviour Change Technique Taxonomy version 1, and Theoretical Domains Framework). Systematic review 2: quantitative, qualitative, mixed-methods research on patient/provider experiences. Study quality assessed using revised Cochrane risk-of-bias tool for randomised trials; Risk Of Bias In Non-randomised Studies - of Interventions and Mixed Methods Appraisal Tool.</p><p><strong>Results: </strong>Fifty-three articles (41 studies) were included in systematic review 1, and 28 articles (28 studies) in systematic review 2. Eleven randomised controlled trials demonstrated that behaviour change technique-based interventions increased daily physical activity in the short term [increase of 0.20 standardised mean difference (95% confidence interval 0.07 to 0.33), ~ 473 steps/day] with high certainty. Evidence of maintenance of daily physical activity is unclear (increase of 0.12 standardised mean difference; ~ 288 steps/day). Behaviour change techniques aimed at improving patients' intentions to engage in physical activity were most effective. Network analysis suggests that behaviour change technique-based interventions improved daily physical activity and may be better than supervised exercise therapy in maintaining daily physical activity. behaviour change technique-based interventions were acceptable and had short-medium-term benefits to initial/absolute claudication distance/time, walking impairment scores and disease-specific quality of life.</p><p><strong>Conclusions: </strong>The behaviour change technique-based interventions are effective, targeting intention to engage in physical activity, in improving daily physical activity","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 18","pages":"1-142"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eleni Gkini, Rachel L Adams, Daniella Spittle, Paul Ellis, Katherine Allsopp, Sanya Saleem, Matthew McKenna, Nick le Mesurier, Nicola Gale, Sarah Tearne, Peymane Adab, Rachel E Jordan, Nawar Diar Bakerly, Alice M Turner
Background: Chronic obstructive pulmonary disease exacerbations (acute exacerbation of chronic obstructive pulmonary disease) are characterised by increased sputum volume, purulence and breathlessness. Patients are encouraged to recognise and treat acute exacerbation of chronic obstructive pulmonary disease as part of a self-management plan. Only half of acute exacerbation of chronic obstructive pulmonary disease are caused by bacterial infection, but self-management plans generally advocate use of antibiotics and steroids for all events, hence antibiotics may be overused. Sputum colour relates closely to bacterial load; thus it could determine whether antibiotics are appropriate. This pragmatic randomised controlled trial tested whether use of a sputum colour chart is safe and effective in United Kingdom primary care.
Methods: Colour chronic obstructive pulmonary disease was a multicentre, randomised controlled trial in adults with chronic obstructive pulmonary disease who had ≥ 2 acute exacerbations of chronic obstructive pulmonary disease or ≥ 1 hospital admission for acute exacerbation of chronic obstructive pulmonary disease in the preceding year. The primary objective was to demonstrate that the Bronkotest® (London) sputum colour chart is non-inferior to usual care (safe). The primary outcome was rate of hospital admission for acute exacerbation of chronic obstructive pulmonary disease at 12 months; secondary outcomes included requirement for second courses of treatment and quality of life (chronic obstructive pulmonary disease assessment test score). Nested substudies examining daily symptoms via an e-diary and sputum culture assessed untreated acute exacerbation of chronic obstructive pulmonary disease rate and antibiotic resistance, respectively. A process evaluation examined trial fidelity and acceptability of the intervention, employing qualitative research methods incorporating patients as co-researchers.
Limitations: The study was terminated early due to low recruitment (115/2954 planned sample size).
Results: One hundred and fifteen patients were recruited and randomised 1 : 1 to colour chart use or usual care; they generally had severe Global Initiative for Chronic Obstructive Lung Disease D chronic obstructive pulmonary disease, with significant breathlessness (54% Medical Research Council score of 4 or 5) and poor quality of life (chronic obstructive pulmonary disease assessment test score at baseline 24). Comorbid respiratory and systemic disease was common. Self-management was delivered well in both arms, and the colour chart acceptable to patients and staff; no specific issues for patients with multiple long-term conditions were identified. Hospital admissions for acute exacerbation of chronic obstructive pulmonary disease tended to occur more in colour chart users [32 vs. 16%, relative risk 1.95 (0.92 to 4.18)], and antibiotic
背景：慢性阻塞性肺疾病急性加重（慢性阻塞性肺疾病急性加重）的特征是痰量增加、化脓和呼吸困难。作为自我管理计划的一部分，鼓励患者认识和治疗慢性阻塞性肺疾病的急性加重。慢性阻塞性肺疾病急性加重中只有一半是由细菌感染引起的，但自我管理计划通常主张对所有事件使用抗生素和类固醇，因此抗生素可能被过度使用。痰液颜色与细菌负荷密切相关；因此，它可以确定抗生素是否合适。这项实用的随机对照试验测试了在英国初级保健中使用痰液颜色表是否安全有效。方法：彩色慢性阻塞性肺疾病是一项多中心、随机对照试验，研究对象为成人慢性阻塞性肺疾病患者，这些患者在前一年有≥2次慢性阻塞性肺疾病急性加重或≥1次慢性阻塞性肺疾病急性加重住院。主要目的是证明Bronkotest®（London）痰液颜色图不逊于常规护理（安全）。主要终点为慢性阻塞性肺疾病急性加重12个月住院率；次要结局包括对第二疗程的要求和生活质量（慢性阻塞性肺疾病评估测试得分）。巢式亚研究通过电子日记和痰培养检查每日症状，分别评估未经治疗的慢性阻塞性肺疾病急性加重率和抗生素耐药性。过程评估检查了试验的保真度和干预的可接受性，采用定性研究方法，将患者作为共同研究人员。局限性：由于招募人数少（115/2954计划样本量），研究提前终止。结果：115例患者被招募并随机分为1∶1组，使用彩色图表或常规护理；他们通常患有严重的慢性阻塞性肺疾病全球倡议D慢性阻塞性肺疾病，伴有明显的呼吸困难（54%的医学研究委员会评分为4或5）和生活质量差（慢性阻塞性肺疾病评估测试基线评分为24）。呼吸道和全身性疾病合并症很常见。两组的自我管理都很好，患者和工作人员都能接受彩色图表；没有发现患有多种长期疾病的患者的具体问题。慢性阻塞性肺疾病急性加重住院在彩色图表使用者中更容易发生[32比16%，相对危险度1.95(0.92至4.18)]，慢性阻塞性肺疾病首次急性加重治疗后14天内的抗生素疗程也更常见[34比18%，调整相对危险度1.80(0.85至3.79)]。尽管如此，彩色图表使用者在12个月时的生活质量更好[慢性阻塞性肺疾病评估测试19.9 vs. -24.5，调整后平均差-2.95(-5.93至-0.04)]。38名患者同意痰液亚组研究，接受了57份样本（42份处于稳定状态，15份处于慢性阻塞性肺疾病急性加重期），其中30%含有潜在致病菌。支气管扩张受试者的痰更有可能是化脓的，与疾病状态（稳定还是恶化）或样本是否对潜在致病菌呈阳性无关，这表明仅凭颜色不能用于指导抗生素的使用。11名患者完成了电子日记研究，并捕获了42例症状定义的慢性阻塞性肺疾病急性加重事件，其中许多未经治疗，慢性肺病工具评分低于接受治疗的患者。未处理的事件解决得较慢。由于数量少，研究组之间的差异没有意义。结论和未来的工作：我们的结果表明Bronkotest痰色图不太可能成为初级保健中慢性阻塞性肺疾病患者自我管理的有用补充，但需要进一步的工作来证实这一点。资助：本摘要介绍了由国家卫生与保健研究所（NIHR）卫生技术评估项目资助的独立研究，奖励号为17/128/04。
{"title":"Sputum colour charts to guide antibiotic self-treatment of acute exacerbation of chronic obstructive pulmonary disease: the Colour-COPD RCT.","authors":"Eleni Gkini, Rachel L Adams, Daniella Spittle, Paul Ellis, Katherine Allsopp, Sanya Saleem, Matthew McKenna, Nick le Mesurier, Nicola Gale, Sarah Tearne, Peymane Adab, Rachel E Jordan, Nawar Diar Bakerly, Alice M Turner","doi":"10.3310/KPFD5558","DOIUrl":"10.3310/KPFD5558","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease exacerbations (acute exacerbation of chronic obstructive pulmonary disease) are characterised by increased sputum volume, purulence and breathlessness. Patients are encouraged to recognise and treat acute exacerbation of chronic obstructive pulmonary disease as part of a self-management plan. Only half of acute exacerbation of chronic obstructive pulmonary disease are caused by bacterial infection, but self-management plans generally advocate use of antibiotics and steroids for all events, hence antibiotics may be overused. Sputum colour relates closely to bacterial load; thus it could determine whether antibiotics are appropriate. This pragmatic randomised controlled trial tested whether use of a sputum colour chart is safe and effective in United Kingdom primary care.</p><p><strong>Methods: </strong>Colour chronic obstructive pulmonary disease was a multicentre, randomised controlled trial in adults with chronic obstructive pulmonary disease who had ≥ 2 acute exacerbations of chronic obstructive pulmonary disease or ≥ 1 hospital admission for acute exacerbation of chronic obstructive pulmonary disease in the preceding year. The primary objective was to demonstrate that the Bronkotest<sup>®</sup> (London) sputum colour chart is non-inferior to usual care (safe). The primary outcome was rate of hospital admission for acute exacerbation of chronic obstructive pulmonary disease at 12 months; secondary outcomes included requirement for second courses of treatment and quality of life (chronic obstructive pulmonary disease assessment test score). Nested substudies examining daily symptoms via an e-diary and sputum culture assessed untreated acute exacerbation of chronic obstructive pulmonary disease rate and antibiotic resistance, respectively. A process evaluation examined trial fidelity and acceptability of the intervention, employing qualitative research methods incorporating patients as co-researchers.</p><p><strong>Limitations: </strong>The study was terminated early due to low recruitment (115/2954 planned sample size).</p><p><strong>Results: </strong>One hundred and fifteen patients were recruited and randomised 1 : 1 to colour chart use or usual care; they generally had severe Global Initiative for Chronic Obstructive Lung Disease D chronic obstructive pulmonary disease, with significant breathlessness (54% Medical Research Council score of 4 or 5) and poor quality of life (chronic obstructive pulmonary disease assessment test score at baseline 24). Comorbid respiratory and systemic disease was common. Self-management was delivered well in both arms, and the colour chart acceptable to patients and staff; no specific issues for patients with multiple long-term conditions were identified. Hospital admissions for acute exacerbation of chronic obstructive pulmonary disease tended to occur more in colour chart users [32 vs. 16%, relative risk 1.95 (0.92 to 4.18)], and antibiotic ","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-42"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Graham Devereux, Seonaidh Cotton, Mintu Nath, Nicola McMeekin, Karen Campbell, Rekha Chaudhuri, Gourab Choudhury, Anthony De Soyza, Shona Fielding, Simon Gompertz, John Haughney, Amanda Lee, Graeme MacLennan, Alyn Morice, John Norrie, David Price, Philip Short, Jorgen Vestbo, Paul Walker, Jadwiga Wedzicha, Andrew Wilson, Olivia Wu, Brian Lipworth
Background: Observational studies of people with chronic obstructive pulmonary disease using beta-blockers for cardiovascular disease indicate that beta-blocker use is associated with reduced risk of chronic obstructive pulmonary disease exacerbation. However, at the time this study was initiated, there had been no randomised controlled trials confirming or refuting this.
Objective(s): To determine the clinical and cost-effectiveness of adding bisoprolol (maximal dose 5 mg once daily) to usual chronic obstructive pulmonary disease therapies in patients with chronic obstructive pulmonary disease at high risk of exacerbation.
Design: A multicentre, pragmatic, double-blind, randomised, placebo-controlled clinical trial.
Setting: Seventy-six United Kingdom primary and secondary care sites.
Participants: People aged ≥ 40 years with a diagnosis of at least moderately severe chronic obstructive pulmonary disease with a history of at least two exacerbations in the previous year.
Interventions: Participants were randomised (1 : 1) to receive either bisoprolol or placebo for 1 year. During a 4- to 7-week titration period, the maximum tolerated dose was established (1.25 mg, 2.5 mg, 3.75 mg, 5 mg once daily).
Primary outcome: A number of participant-reported exacerbations during the 1-year treatment period.
Results: In total, 519 participants were recruited and randomised. Four post-randomisation exclusions left 259 in the bisoprolol group and 256 in the placebo group. Treatment groups were balanced at baseline: mean (standard deviation) age 68 (7.9) years; 53% men; mean (standard deviation) pack year smoking history 45 (25.2); mean (standard deviation) 3.5 (1.9) exacerbations in previous year. Primary outcome data were available for 99.8% of participants (bisoprolol 259, placebo 255). The mean (standard deviation) number of exacerbations was 2.03 (1.91) in the bisoprolol group and 2.01 (1.75) in the placebo group (adjusted incidence rate ratio 0.97, 95% confidence interval 0.84 to 1.13), p = 0.72. The number of participants with serious adverse events was similar between the two groups (bisoprolol 37, placebo 36). The total number of adverse reactions was also similar between the two groups. As expected, bisoprolol was associated with a higher proportion of vascular adverse reactions (e.g. hypotension, cold peripheries) than placebo, but was not associated with an excess of other adverse reactions, including those classified as respiratory. Adding bisoprolol resulted in a statistically insignificant trend towards higher costs (£636, 95% confidence interval £118 to £1391) and fewer quality-adjusted life-years (0.035, 95% confidence interval 0.059 to 0.010) compared to placebo.
Limitations: The study findings should be interpreted with caution as the
{"title":"Bisoprolol for patients with chronic obstructive pulmonary disease at high risk of exacerbation: the BICS RCT.","authors":"Graham Devereux, Seonaidh Cotton, Mintu Nath, Nicola McMeekin, Karen Campbell, Rekha Chaudhuri, Gourab Choudhury, Anthony De Soyza, Shona Fielding, Simon Gompertz, John Haughney, Amanda Lee, Graeme MacLennan, Alyn Morice, John Norrie, David Price, Philip Short, Jorgen Vestbo, Paul Walker, Jadwiga Wedzicha, Andrew Wilson, Olivia Wu, Brian Lipworth","doi":"10.3310/TNDG8641","DOIUrl":"10.3310/TNDG8641","url":null,"abstract":"<p><strong>Background: </strong>Observational studies of people with chronic obstructive pulmonary disease using beta-blockers for cardiovascular disease indicate that beta-blocker use is associated with reduced risk of chronic obstructive pulmonary disease exacerbation. However, at the time this study was initiated, there had been no randomised controlled trials confirming or refuting this.</p><p><strong>Objective(s): </strong>To determine the clinical and cost-effectiveness of adding bisoprolol (maximal dose 5 mg once daily) to usual chronic obstructive pulmonary disease therapies in patients with chronic obstructive pulmonary disease at high risk of exacerbation.</p><p><strong>Design: </strong>A multicentre, pragmatic, double-blind, randomised, placebo-controlled clinical trial.</p><p><strong>Setting: </strong>Seventy-six United Kingdom primary and secondary care sites.</p><p><strong>Participants: </strong>People aged ≥ 40 years with a diagnosis of at least moderately severe chronic obstructive pulmonary disease with a history of at least two exacerbations in the previous year.</p><p><strong>Interventions: </strong>Participants were randomised (1 : 1) to receive either bisoprolol or placebo for 1 year. During a 4- to 7-week titration period, the maximum tolerated dose was established (1.25 mg, 2.5 mg, 3.75 mg, 5 mg once daily).</p><p><strong>Primary outcome: </strong>A number of participant-reported exacerbations during the 1-year treatment period.</p><p><strong>Results: </strong>In total, 519 participants were recruited and randomised. Four post-randomisation exclusions left 259 in the bisoprolol group and 256 in the placebo group. Treatment groups were balanced at baseline: mean (standard deviation) age 68 (7.9) years; 53% men; mean (standard deviation) pack year smoking history 45 (25.2); mean (standard deviation) 3.5 (1.9) exacerbations in previous year. Primary outcome data were available for 99.8% of participants (bisoprolol 259, placebo 255). The mean (standard deviation) number of exacerbations was 2.03 (1.91) in the bisoprolol group and 2.01 (1.75) in the placebo group (adjusted incidence rate ratio 0.97, 95% confidence interval 0.84 to 1.13), <i>p</i> = 0.72. The number of participants with serious adverse events was similar between the two groups (bisoprolol 37, placebo 36). The total number of adverse reactions was also similar between the two groups. As expected, bisoprolol was associated with a higher proportion of vascular adverse reactions (e.g. hypotension, cold peripheries) than placebo, but was not associated with an excess of other adverse reactions, including those classified as respiratory. Adding bisoprolol resulted in a statistically insignificant trend towards higher costs (£636, 95% confidence interval £118 to £1391) and fewer quality-adjusted life-years (0.035, 95% confidence interval 0.059 to 0.010) compared to placebo.</p><p><strong>Limitations: </strong>The study findings should be interpreted with caution as the ","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 17","pages":"1-97"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hamish McAllister-Williams, Nicola Goudie, Lumbini Azim, Victoria Bartle, Michael Berger, Chrissie Butcher, Thomas Chadwick, Emily Clare, Paul Courtney, Lyndsey Dixon, Nichola Duffelen, Tony Fouweather, William Gann, John Geddes, Sumeet Gupta, Beth Hall, Timea Helter, Paul Hindmarch, Eva-Maria Holstein, Ward Lawrence, Phil Mawson, Iain McKinnon, Adam Milne, Aisling Molloy, Abigail Moore, Richard Morriss, Anisha Nakulan, Judit Simon, Daniel Smith, Bryony Stokes-Crossley, Paul Stokes, Andrew Swain, Zoë Walmsley, Christopher Weetman, Allan H Young, Stuart Watson
<p><strong>Background: </strong>There are limited options currently recommended in National Institute for Health and Care Excellence guidelines for the treatment of bipolar depression. Pramipexole has been shown to improve mood symptoms in two small pilot studies in such patients.</p><p><strong>Objectives: </strong>Primary: to evaluate the clinical effectiveness of pramipexole versus placebo alongside routine mood-stabilising medications over 12 weeks in patients with treatment-resistant bipolar depression. Secondary: evaluate the impact of pramipexole on mood and anxiety, psychosocial function, cost-effectiveness, and safety and tolerability over 48 weeks.</p><p><strong>Design: </strong>Multicentre, randomised, placebo-controlled trial of pramipexole versus placebo in addition to standard-of-care mood stabilisers. Clinicians, researchers and participants were blinded throughout the duration of the study. Pre-randomisation stage (to adjust antipsychotics or commence mood stabilisers where required) before randomisation. Weekly online assessments of mood and anxiety from randomisation to week 52, with psychosocial function, quality of life and healthcare resource utilisation assessments conducted at regular intervals.</p><p><strong>Setting: </strong>Twenty-one National Health Service trusts and Health Boards across England and Scotland.</p><p><strong>Participants: </strong>Patients aged 18 years and over with a diagnosis of treatment-resistant bipolar depression currently under secondary care mental health services. Aim to randomise 290 participants.</p><p><strong>Interventions: </strong>Pramipexole or matched placebo orally once daily, titrated from 0.25 mg to maximum of 2.5 mg (salt weight) depending on efficacy and tolerability.</p><p><strong>Main outcome measures: </strong>Depression - Quick Inventory for Depressive Symptomology; anxiety - Generalised Anxiety Disorder-7-item scale; psychosocial functioning - Work and Social Adjustment Scale; hypomania/mania - Altman Self-rating Scale of Mania; tolerability - Treatment Satisfaction Questionnaire for Medication; well-being and quality of life - EuroQol-5 Dimensions, five-level version, ICEpop CAPability measure for Adults and Oxford CAPabilities questionnaire-Mental Health tools.</p><p><strong>Results: </strong>Thirty-nine participants randomised (18 to pramipexole and 21 to placebo) with 36 providing data for the primary analysis. Pramipexole led to greater reductions in depressive symptoms at 12 weeks compared to placebo [4.4 (4.8) vs. 2.1 (5.1)]: a medium-sized (<i>d</i> = -0.72) but not statistically significant difference (95% confidence interval -0.4 to 6.3; <i>p</i> = 0.087). There were some statistically significant positive effects of pramipexole on secondary outcomes (reduction in depressive symptoms at 36 weeks, response and remission rates at trial exit, psychosocial function). Pramipexole was associated with an increased rate of hypomania/manic symptoms, but this appeared to be redu
{"title":"Pramipexole in addition to mood stabilisers for treatment-resistant bipolar depression: the PAX-BD randomised double-blind placebo-controlled trial.","authors":"Hamish McAllister-Williams, Nicola Goudie, Lumbini Azim, Victoria Bartle, Michael Berger, Chrissie Butcher, Thomas Chadwick, Emily Clare, Paul Courtney, Lyndsey Dixon, Nichola Duffelen, Tony Fouweather, William Gann, John Geddes, Sumeet Gupta, Beth Hall, Timea Helter, Paul Hindmarch, Eva-Maria Holstein, Ward Lawrence, Phil Mawson, Iain McKinnon, Adam Milne, Aisling Molloy, Abigail Moore, Richard Morriss, Anisha Nakulan, Judit Simon, Daniel Smith, Bryony Stokes-Crossley, Paul Stokes, Andrew Swain, Zoë Walmsley, Christopher Weetman, Allan H Young, Stuart Watson","doi":"10.3310/HBFC1953","DOIUrl":"10.3310/HBFC1953","url":null,"abstract":"<p><strong>Background: </strong>There are limited options currently recommended in National Institute for Health and Care Excellence guidelines for the treatment of bipolar depression. Pramipexole has been shown to improve mood symptoms in two small pilot studies in such patients.</p><p><strong>Objectives: </strong>Primary: to evaluate the clinical effectiveness of pramipexole versus placebo alongside routine mood-stabilising medications over 12 weeks in patients with treatment-resistant bipolar depression. Secondary: evaluate the impact of pramipexole on mood and anxiety, psychosocial function, cost-effectiveness, and safety and tolerability over 48 weeks.</p><p><strong>Design: </strong>Multicentre, randomised, placebo-controlled trial of pramipexole versus placebo in addition to standard-of-care mood stabilisers. Clinicians, researchers and participants were blinded throughout the duration of the study. Pre-randomisation stage (to adjust antipsychotics or commence mood stabilisers where required) before randomisation. Weekly online assessments of mood and anxiety from randomisation to week 52, with psychosocial function, quality of life and healthcare resource utilisation assessments conducted at regular intervals.</p><p><strong>Setting: </strong>Twenty-one National Health Service trusts and Health Boards across England and Scotland.</p><p><strong>Participants: </strong>Patients aged 18 years and over with a diagnosis of treatment-resistant bipolar depression currently under secondary care mental health services. Aim to randomise 290 participants.</p><p><strong>Interventions: </strong>Pramipexole or matched placebo orally once daily, titrated from 0.25 mg to maximum of 2.5 mg (salt weight) depending on efficacy and tolerability.</p><p><strong>Main outcome measures: </strong>Depression - Quick Inventory for Depressive Symptomology; anxiety - Generalised Anxiety Disorder-7-item scale; psychosocial functioning - Work and Social Adjustment Scale; hypomania/mania - Altman Self-rating Scale of Mania; tolerability - Treatment Satisfaction Questionnaire for Medication; well-being and quality of life - EuroQol-5 Dimensions, five-level version, ICEpop CAPability measure for Adults and Oxford CAPabilities questionnaire-Mental Health tools.</p><p><strong>Results: </strong>Thirty-nine participants randomised (18 to pramipexole and 21 to placebo) with 36 providing data for the primary analysis. Pramipexole led to greater reductions in depressive symptoms at 12 weeks compared to placebo [4.4 (4.8) vs. 2.1 (5.1)]: a medium-sized (<i>d</i> = -0.72) but not statistically significant difference (95% confidence interval -0.4 to 6.3; <i>p</i> = 0.087). There were some statistically significant positive effects of pramipexole on secondary outcomes (reduction in depressive symptoms at 36 weeks, response and remission rates at trial exit, psychosocial function). Pramipexole was associated with an increased rate of hypomania/manic symptoms, but this appeared to be redu","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 21","pages":"1-216"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mark Simmonds, Matthew Walton, Rob Hodgson, Alexis Llewellyn, Ruth Walker, Helen Fulbright, Laura Bojke, Lesley Stewart, Sofia Dias, Thomas Rush, John Lawrenson, Tunde Peto, David Steel
<p><strong>Background: </strong>Diabetic retinopathy is a major cause of sight loss in people with diabetes, with a high risk of macular oedema, vitreous haemorrhage or other complications. Panretinal photocoagulation is the primary treatment for proliferative retinopathy. Anti-vascular endothelial growth factor drugs are used to treat various eye conditions and may be beneficial for people with proliferative or non-proliferative retinopathy.</p><p><strong>Methods: </strong>The Anti-VEGF In Diabetes project sought to investigate the clinical and cost-effectiveness of using anti-vascular endothelial growth factor to prevent retinopathy progression when compared to panretinal photocoagulation or no treatment. A systematic review with network meta-analysis of randomised controlled trials of anti-vascular endothelial growth factor (alone or in combination with panretinal photocoagulation) to treat retinopathy was conducted. The database searches were updated in May 2023. Individual participant data from larger trials were sought. A systematic review of non-randomised studies was performed. Existing cost-effectiveness analyses were reviewed, and a new economic model was developed, informed by the individual participant data meta-analysis. The model also estimated the value of undertaking further research to resolve decision uncertainty.</p><p><strong>Results: </strong>The review found that anti-vascular endothelial growth factors produced a slight, and not clinically meaningful, benefit over panretinal photocoagulation in best corrected visual acuity, after 1 year of follow-up in people with proliferative retinopathy (mean difference of 4.5 ETDRS letters; 95% credible interval -0.7 to 8.2). There was no evidence of a difference in effectiveness among the different anti-vascular endothelial growth factors. The benefit of anti-vascular endothelial growth factor appears to decline over time. Anti-vascular endothelial growth factor therapy may be more effective in people with poorer initial visual acuity. Anti-vascular endothelial growth factor had no impact on vision in people with non-proliferative retinopathy. Anti-vascular endothelial growth factor reduces rates of macular oedema and vitreous haemorrhage and may slow down the progression of retinopathy. Anti-vascular endothelial growth factors were predicted to be more costly but similarly effective to panretinal photocoagulation, with a net health benefit of -0.214 quality-adjusted life-years at a £20,000 willingness-to-pay threshold. Only under very select conditions might anti-vascular endothelial growth factors have the potential for cost-effectiveness to treat proliferative retinopathy. There is potentially significant value in reducing uncertainty through further primary research.</p><p><strong>Conclusions: </strong>Anti-vascular endothelial growth factor has no clinically meaningful benefit over panretinal photocoagulation for preserving visual acuity, but it may delay or prevent progression to
{"title":"Anti-VEGF drugs compared with laser photocoagulation for the treatment of diabetic retinopathy: a systematic review and economic analysis.","authors":"Mark Simmonds, Matthew Walton, Rob Hodgson, Alexis Llewellyn, Ruth Walker, Helen Fulbright, Laura Bojke, Lesley Stewart, Sofia Dias, Thomas Rush, John Lawrenson, Tunde Peto, David Steel","doi":"10.3310/KRWP1264","DOIUrl":"10.3310/KRWP1264","url":null,"abstract":"<p><strong>Background: </strong>Diabetic retinopathy is a major cause of sight loss in people with diabetes, with a high risk of macular oedema, vitreous haemorrhage or other complications. Panretinal photocoagulation is the primary treatment for proliferative retinopathy. Anti-vascular endothelial growth factor drugs are used to treat various eye conditions and may be beneficial for people with proliferative or non-proliferative retinopathy.</p><p><strong>Methods: </strong>The Anti-VEGF In Diabetes project sought to investigate the clinical and cost-effectiveness of using anti-vascular endothelial growth factor to prevent retinopathy progression when compared to panretinal photocoagulation or no treatment. A systematic review with network meta-analysis of randomised controlled trials of anti-vascular endothelial growth factor (alone or in combination with panretinal photocoagulation) to treat retinopathy was conducted. The database searches were updated in May 2023. Individual participant data from larger trials were sought. A systematic review of non-randomised studies was performed. Existing cost-effectiveness analyses were reviewed, and a new economic model was developed, informed by the individual participant data meta-analysis. The model also estimated the value of undertaking further research to resolve decision uncertainty.</p><p><strong>Results: </strong>The review found that anti-vascular endothelial growth factors produced a slight, and not clinically meaningful, benefit over panretinal photocoagulation in best corrected visual acuity, after 1 year of follow-up in people with proliferative retinopathy (mean difference of 4.5 ETDRS letters; 95% credible interval -0.7 to 8.2). There was no evidence of a difference in effectiveness among the different anti-vascular endothelial growth factors. The benefit of anti-vascular endothelial growth factor appears to decline over time. Anti-vascular endothelial growth factor therapy may be more effective in people with poorer initial visual acuity. Anti-vascular endothelial growth factor had no impact on vision in people with non-proliferative retinopathy. Anti-vascular endothelial growth factor reduces rates of macular oedema and vitreous haemorrhage and may slow down the progression of retinopathy. Anti-vascular endothelial growth factors were predicted to be more costly but similarly effective to panretinal photocoagulation, with a net health benefit of -0.214 quality-adjusted life-years at a £20,000 willingness-to-pay threshold. Only under very select conditions might anti-vascular endothelial growth factors have the potential for cost-effectiveness to treat proliferative retinopathy. There is potentially significant value in reducing uncertainty through further primary research.</p><p><strong>Conclusions: </strong>Anti-vascular endothelial growth factor has no clinically meaningful benefit over panretinal photocoagulation for preserving visual acuity, but it may delay or prevent progression to","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-16"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jehan N Karim, Helen Campbell, Pranav Pandya, Edward C F Wilson, Zarko Alfirevic, Trish Chudleigh, Elizabeth Duff, Jane Fisher, Hilary Goodman, Lisa Hinton, Christos Ioannou, Edmund Juszczak, Louise Linsell, Heather L Longworth, Kypros H Nicolaides, Anne Rhodes, Gordon Smith, Basky Thilaganathan, Jim Thornton, Gillian Yaz, Oliver Rivero-Arias, Aris T Papageorghiou
<p><strong>Background: </strong>In the United Kingdom, pregnant women are offered two scans: at 11-14 and 18-20 weeks' gestation. Current guidance supports fetal anatomical screening at the second scan, but evidence suggests earlier detection is possible.</p><p><strong>Objectives: </strong>To determine clinical and cost-effectiveness of a detailed two-dimensional ultrasound scan in the first trimester for detection of fetal anomalies, in addition to usual practice.</p><p><strong>Design: </strong>Systematic review and meta-analysis. Nationwide survey. Analysis of National Congenital Anomaly Disease Registry data. Consensus procedure. Prospective survey of parental opinions. Probabilistic decision-analytic model for cost-effectiveness. Value-of-information analysis.</p><p><strong>Setting: </strong>United Kingdom National Health Service.</p><p><strong>Participants: </strong>Pregnant women and partners.</p><p><strong>Interventions: </strong>Detailed anomaly ultrasound at 11-14 weeks' gestation, in addition to usual practice.</p><p><strong>Main outcome measures: </strong>Diagnostic accuracy, protocol development, health economic modelling and value-of-information analysis.</p><p><strong>Data sources: </strong>MEDLINE (OvidSP), EMBASE (OvidSP), Science Citation Index and Conference Proceedings Citation Index-Science (Web of Science Core Collection); National Congenital Anomaly Disease Registry; European Congenital Anomalies Registry; Surveys of National Health Service Trusts; screening sonographers, midwives and doctors; and parents; National Schedule of National Health Service Costs (2019-20).</p><p><strong>Review methods: </strong>Systematic review and meta-analysis for diagnostic accuracy.</p><p><strong>Results: </strong>First-trimester ultrasound detects 93.3% (95% confidence interval 90.4% to 95.7%) of a pre-selected group of eight major anomalies with specificity of 99.99% (95% confidence interval 99.98% to 99.99%) and positive predictive value of 96.5% (95% confidence interval 93.3 to 98.8, 416,877 fetuses, 40 studies). For major cardiac anomalies, the respective data are 55.8% (95% confidence interval 45.9% to 65.5%), 99.98% (95% confidence interval 99.97% to 99.99%) and 94.85% (95% confidence interval 91.63% to 97.32%, 306,872 fetuses, 45 studies). Of NHS trusts surveyed, 77% currently perform first-trimester anatomy assessment, with evidence of inequity of care; earlier screening resulted in more diagnoses before 16 weeks' gestation. A consensus procedure (<i>n</i> = 172) developed an anatomical protocol and minimum targets for diagnosis. Parental survey (<i>n</i> = 1374) indicated that over 90% would opt for such screening. Modelling of singleton pregnancies undergoing earlier anomaly screening using two-dimensional ultrasound was associated with increased mean healthcare costs per woman (£11, 95% confidence interval £1 to £29) and maternal quality-adjusted life-years (0.002065, 95% confidence interval 0.000565 to 0.00358), an incremental co
{"title":"Clinical and cost-effectiveness of detailed anomaly ultrasound screening in the first trimester: a mixed-methods study.","authors":"Jehan N Karim, Helen Campbell, Pranav Pandya, Edward C F Wilson, Zarko Alfirevic, Trish Chudleigh, Elizabeth Duff, Jane Fisher, Hilary Goodman, Lisa Hinton, Christos Ioannou, Edmund Juszczak, Louise Linsell, Heather L Longworth, Kypros H Nicolaides, Anne Rhodes, Gordon Smith, Basky Thilaganathan, Jim Thornton, Gillian Yaz, Oliver Rivero-Arias, Aris T Papageorghiou","doi":"10.3310/NLTP7102","DOIUrl":"10.3310/NLTP7102","url":null,"abstract":"<p><strong>Background: </strong>In the United Kingdom, pregnant women are offered two scans: at 11-14 and 18-20 weeks' gestation. Current guidance supports fetal anatomical screening at the second scan, but evidence suggests earlier detection is possible.</p><p><strong>Objectives: </strong>To determine clinical and cost-effectiveness of a detailed two-dimensional ultrasound scan in the first trimester for detection of fetal anomalies, in addition to usual practice.</p><p><strong>Design: </strong>Systematic review and meta-analysis. Nationwide survey. Analysis of National Congenital Anomaly Disease Registry data. Consensus procedure. Prospective survey of parental opinions. Probabilistic decision-analytic model for cost-effectiveness. Value-of-information analysis.</p><p><strong>Setting: </strong>United Kingdom National Health Service.</p><p><strong>Participants: </strong>Pregnant women and partners.</p><p><strong>Interventions: </strong>Detailed anomaly ultrasound at 11-14 weeks' gestation, in addition to usual practice.</p><p><strong>Main outcome measures: </strong>Diagnostic accuracy, protocol development, health economic modelling and value-of-information analysis.</p><p><strong>Data sources: </strong>MEDLINE (OvidSP), EMBASE (OvidSP), Science Citation Index and Conference Proceedings Citation Index-Science (Web of Science Core Collection); National Congenital Anomaly Disease Registry; European Congenital Anomalies Registry; Surveys of National Health Service Trusts; screening sonographers, midwives and doctors; and parents; National Schedule of National Health Service Costs (2019-20).</p><p><strong>Review methods: </strong>Systematic review and meta-analysis for diagnostic accuracy.</p><p><strong>Results: </strong>First-trimester ultrasound detects 93.3% (95% confidence interval 90.4% to 95.7%) of a pre-selected group of eight major anomalies with specificity of 99.99% (95% confidence interval 99.98% to 99.99%) and positive predictive value of 96.5% (95% confidence interval 93.3 to 98.8, 416,877 fetuses, 40 studies). For major cardiac anomalies, the respective data are 55.8% (95% confidence interval 45.9% to 65.5%), 99.98% (95% confidence interval 99.97% to 99.99%) and 94.85% (95% confidence interval 91.63% to 97.32%, 306,872 fetuses, 45 studies). Of NHS trusts surveyed, 77% currently perform first-trimester anatomy assessment, with evidence of inequity of care; earlier screening resulted in more diagnoses before 16 weeks' gestation. A consensus procedure (<i>n</i> = 172) developed an anatomical protocol and minimum targets for diagnosis. Parental survey (<i>n</i> = 1374) indicated that over 90% would opt for such screening. Modelling of singleton pregnancies undergoing earlier anomaly screening using two-dimensional ultrasound was associated with increased mean healthcare costs per woman (£11, 95% confidence interval £1 to £29) and maternal quality-adjusted life-years (0.002065, 95% confidence interval 0.000565 to 0.00358), an incremental co","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 22","pages":"1-250"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julia Geppert, Peter Auguste, Asra Asgharzadeh, Hesam Ghiasvand, Mubarak Patel, Anna Brown, Surangi Jayakody, Emma Helm, Dan Todkill, Jason Madan, Chris Stinton, Daniel Gallacher, Sian Taylor-Phillips, Yen-Fu Chen
<p><strong>Background: </strong>Lung cancer is one of the most common types of cancer and the leading cause of cancer death in the United Kingdom. Artificial intelligence-based software has been developed to reduce the number of missed or misdiagnosed lung nodules on computed tomography images.</p><p><strong>Objective: </strong> To assess the accuracy, clinical effectiveness and cost-effectiveness of using software with artificial intelligence-derived algorithms to assist in the detection and analysis of lung nodules in computed tomography scans of the chest compared with unassisted reading.</p><p><strong>Design: </strong>Systematic review and de novo cost-effectiveness analysis.</p><p><strong>Methods: </strong>Searches were undertaken from 2012 to January 2022. Company submissions were accepted until 31 August 2022. Study quality was assessed using the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2), the extension to QUADAS-2 for assessing risk of bias in comparative accuracy studies (QUADAS-C) and the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist. Outcomes were synthesised narratively. Two decision trees were used for cost-effectiveness: (1) a simple decision tree for the detection of actionable nodules and (2) a decision tree reflecting the full clinical pathways for people undergoing chest computed tomography scans. Models estimated incremental cost-effectiveness ratios, cost per correct detection of an actionable nodule, and cost per cancer detected and treated. We undertook scenario and sensitivity analyses.</p><p><strong>Results: </strong>Twenty-seven studies were included. All were rated as being at high risk of bias. Twenty-four of the included studies used retrospective data sets. Seventeen compared readers with and without artificial intelligence software. One reported prospective screening experiences before and after artificial intelligence software implementation. The remaining studies either evaluated stand-alone artificial intelligence or provided only non-comparative evidence. (1) Artificial intelligence assistance generally improved the detection of any nodules compared with unaided reading (three studies; average per-person sensitivity 0.43-0.68 for unaided and 0.79-0.99 for artificial intelligence-assisted reading), with similar or lower specificity (three studies; 0.77-1.00 for unaided and 0.81-0.97 for artificial intelligence-assisted reading). Nodule diameters were similar or significantly larger with semiautomatic measurements than with manual measurements. Intra-reader and inter-reader agreement in nodule size measurement and in risk classification generally improved with artificial intelligence assistance or were comparable to those with unaided reading. However, the effect on measurement accuracy is unclear. (2) Radiologist reading time generally decreased with artificial intelligence assistance in research settings. (3) Artific
{"title":"Software with artificial intelligence-derived algorithms for detecting and analysing lung nodules in CT scans: systematic review and economic evaluation.","authors":"Julia Geppert, Peter Auguste, Asra Asgharzadeh, Hesam Ghiasvand, Mubarak Patel, Anna Brown, Surangi Jayakody, Emma Helm, Dan Todkill, Jason Madan, Chris Stinton, Daniel Gallacher, Sian Taylor-Phillips, Yen-Fu Chen","doi":"10.3310/JYTW8921","DOIUrl":"10.3310/JYTW8921","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is one of the most common types of cancer and the leading cause of cancer death in the United Kingdom. Artificial intelligence-based software has been developed to reduce the number of missed or misdiagnosed lung nodules on computed tomography images.</p><p><strong>Objective: </strong> To assess the accuracy, clinical effectiveness and cost-effectiveness of using software with artificial intelligence-derived algorithms to assist in the detection and analysis of lung nodules in computed tomography scans of the chest compared with unassisted reading.</p><p><strong>Design: </strong>Systematic review and de novo cost-effectiveness analysis.</p><p><strong>Methods: </strong>Searches were undertaken from 2012 to January 2022. Company submissions were accepted until 31 August 2022. Study quality was assessed using the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2), the extension to QUADAS-2 for assessing risk of bias in comparative accuracy studies (QUADAS-C) and the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist. Outcomes were synthesised narratively. Two decision trees were used for cost-effectiveness: (1) a simple decision tree for the detection of actionable nodules and (2) a decision tree reflecting the full clinical pathways for people undergoing chest computed tomography scans. Models estimated incremental cost-effectiveness ratios, cost per correct detection of an actionable nodule, and cost per cancer detected and treated. We undertook scenario and sensitivity analyses.</p><p><strong>Results: </strong>Twenty-seven studies were included. All were rated as being at high risk of bias. Twenty-four of the included studies used retrospective data sets. Seventeen compared readers with and without artificial intelligence software. One reported prospective screening experiences before and after artificial intelligence software implementation. The remaining studies either evaluated stand-alone artificial intelligence or provided only non-comparative evidence. (1) Artificial intelligence assistance generally improved the detection of any nodules compared with unaided reading (three studies; average per-person sensitivity 0.43-0.68 for unaided and 0.79-0.99 for artificial intelligence-assisted reading), with similar or lower specificity (three studies; 0.77-1.00 for unaided and 0.81-0.97 for artificial intelligence-assisted reading). Nodule diameters were similar or significantly larger with semiautomatic measurements than with manual measurements. Intra-reader and inter-reader agreement in nodule size measurement and in risk classification generally improved with artificial intelligence assistance or were comparable to those with unaided reading. However, the effect on measurement accuracy is unclear. (2) Radiologist reading time generally decreased with artificial intelligence assistance in research settings. (3) Artific","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 14","pages":"1-234"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katie Scandrett, Jill Colquitt, Rachel Court, Fiona Whiter, Bethany Shinkins, Yemisi Takwoingi, Emma Loveman, Daniel Todkill, Paramjit Gill, Daniel Lasserson, Lena Al-Khudairy, Amy Grove, Yen-Fu Chen
Background: This review assessed the clinical- and cost-effectiveness of point-of-care tests to guide the initial management of people presenting with suspected acute respiratory infection.
Methods: Searches for systematic reviews, randomised controlled trials and cost-utility studies were conducted in May 2023. Sources included MEDLINE, Epistemonikos, EMBASE, Cochrane Central Register of Controlled Trials, the Cost-effectiveness Analysis Registry and reference checking. Eligible studies included people (≥ 16 years) making initial contact with the health system with symptoms suggestive of acute respiratory infection. Risk of bias in randomised controlled trials was assessed using the Cochrane risk-of-bias tool. The Drummond checklist was used for cost-utility studies. Meta-analyses of clinical outcomes were conducted to estimate summary risk ratios with 95% confidence intervals. Study characteristics and main results were summarised narratively and tabulated.
Results: Fourteen randomised controlled trials were included; all had a high risk of bias. Ten randomised controlled trials analysed point-of-care tests for C-reactive protein. Compared with usual care, the effects on hospital admissions and mortality were highly uncertain due to sparse data. Three randomised controlled trials had heterogeneous findings on the resolution of symptoms/time to full recovery. The risk of re-consultations increased in patients receiving C-reactive protein point-of-care tests (pooled risk ratio 1.61, 95% confidence interval 1.07 to 2.41; four studies). There was a reduction in antibiotics initially prescribed (C-reactive protein point-of-care tests vs. usual care: pooled risk ratio 0.75, 95% confidence interval 0.68 to 0.84; nine studies). The effects of procalcitonin point-of-care tests compared with usual care on hospital admission, escalation of care, and duration of symptoms were very uncertain as only one randomised controlled trial was included. The study found a large reduction in antibiotic prescriptions within 7 days. Two studies revealed a large reduction in initial antibiotic prescriptions for Group A streptococcus point-of-care tests versus usual care. Only one study compared an influenza point-of-care test with usual care. The effect of the antibiotics prescribed was very uncertain. No deaths occurred in either treatment group.
Cost-effectiveness: Six of the 17 included cost-utility studies were judged to be directly applicable to our review, 4 of which focused on the C-reactive protein point-of-care test. The results suggested that the C-reactive protein point-of-care test is potentially cost-effective; these studies were generally limited to capturing only short-term costs and consequences. One study evaluated 14 different point-of-care tests for Group A streptococcus; none were cost-effective compared with usual care. A further study evaluated two rapid tests (
背景：本综述评估了用于指导疑似急性呼吸道感染患者初始管理的即时检测的临床和成本效益。方法：检索于2023年5月进行的系统评价、随机对照试验和成本-效用研究。来源包括MEDLINE、Epistemonikos、EMBASE、Cochrane Central Register of Controlled Trials、Cost-effectiveness Analysis Registry和参考文献检查。符合条件的研究包括最初与卫生系统接触并有提示急性呼吸道感染症状的人群（≥16岁）。随机对照试验的偏倚风险使用Cochrane偏倚风险工具进行评估。德拉蒙德清单用于成本效用研究。对临床结果进行荟萃分析，以95%的置信区间估计总风险比。对研究特点和主要结果进行叙述总结并制成表格。结果：纳入14项随机对照试验；所有的研究都有很高的偏倚风险。10个随机对照试验分析了c反应蛋白的即时检测。与常规护理相比，由于数据稀疏，对住院率和死亡率的影响高度不确定。三个随机对照试验在症状缓解/完全恢复时间方面有不同的发现。接受c反应蛋白即时检测的患者再次就诊的风险增加(合并风险比1.61,95%可信区间1.07 ~ 2.41；四个研究)。最初处方的抗生素减少(c反应蛋白即时检测与常规治疗相比：合并风险比0.75,95%可信区间0.68至0.84；九个研究)。与常规治疗相比，降钙素原即时检测对入院、治疗升级和症状持续时间的影响非常不确定，因为只纳入了一项随机对照试验。研究发现，抗生素处方在7天内大幅减少。两项研究显示，与常规护理相比，a组链球菌即时检测的初始抗生素处方大幅减少。只有一项研究将流感即时检测与常规护理进行了比较。所开抗生素的效果非常不确定。两组均无死亡病例发生。成本-效果：17项纳入的成本-效用研究中有6项被认为直接适用于我们的综述，其中4项集中于c反应蛋白即时检测。结果表明，c反应蛋白即时检测具有潜在的成本效益；这些研究通常仅限于捕捉短期成本和后果。一项研究评估了14种不同的A群链球菌护理点检测；与常规护理相比，没有一项具有成本效益。进一步的研究评估了两种快速检测方法（Quidel检测流感[Quidel Corp， San Diego， CA， USA]和BinaxNOW [Binax， Inc., Portland， ME, USA]）与培养/血清学相比较，发现它们不具有成本效益。局限性：采用快速合成方法，可能遗漏相关研究。有几个复习问题没有找到证据。结论：c反应蛋白即时检测可减少使用抗生素处方的患者数量，但可增加复诊率。c反应蛋白即时检测可能具有潜在的成本效益，但现有的估计是基于非常小的和不确定的质量调整生命年的收益，并且只考虑了短期成本和后果。其他即时检测的证据非常有限或缺乏。未来的工作：需要进行研究，以探索护理点测试对不同临床环境中分诊决策的影响，并量化其长期健康和成本后果。研究注册：本研究注册号为PROSPERO CRD42023429515。资助：该奖项由美国国家卫生与保健研究所（NIHR）证据综合计划（NIHR奖励编号：NIHR159946）资助，全文发表在《卫生技术评估》上；第29卷第13期有关进一步的奖励信息，请参阅美国国立卫生研究院资助和奖励网站。
{"title":"Rapid tests to inform triage and antibiotic prescribing decisions for adults presenting with suspected acute respiratory infection: a rapid evidence synthesis of clinical effectiveness and cost-utility studies.","authors":"Katie Scandrett, Jill Colquitt, Rachel Court, Fiona Whiter, Bethany Shinkins, Yemisi Takwoingi, Emma Loveman, Daniel Todkill, Paramjit Gill, Daniel Lasserson, Lena Al-Khudairy, Amy Grove, Yen-Fu Chen","doi":"10.3310/KHGP7129","DOIUrl":"10.3310/KHGP7129","url":null,"abstract":"<p><strong>Background: </strong>This review assessed the clinical- and cost-effectiveness of point-of-care tests to guide the initial management of people presenting with suspected acute respiratory infection.</p><p><strong>Methods: </strong>Searches for systematic reviews, randomised controlled trials and cost-utility studies were conducted in May 2023. Sources included MEDLINE, Epistemonikos, EMBASE, Cochrane Central Register of Controlled Trials, the Cost-effectiveness Analysis Registry and reference checking. Eligible studies included people (≥ 16 years) making initial contact with the health system with symptoms suggestive of acute respiratory infection. Risk of bias in randomised controlled trials was assessed using the Cochrane risk-of-bias tool. The Drummond checklist was used for cost-utility studies. Meta-analyses of clinical outcomes were conducted to estimate summary risk ratios with 95% confidence intervals. Study characteristics and main results were summarised narratively and tabulated.</p><p><strong>Results: </strong>Fourteen randomised controlled trials were included; all had a high risk of bias. Ten randomised controlled trials analysed point-of-care tests for C-reactive protein. Compared with usual care, the effects on hospital admissions and mortality were highly uncertain due to sparse data. Three randomised controlled trials had heterogeneous findings on the resolution of symptoms/time to full recovery. The risk of re-consultations increased in patients receiving C-reactive protein point-of-care tests (pooled risk ratio 1.61, 95% confidence interval 1.07 to 2.41; four studies). There was a reduction in antibiotics initially prescribed (C-reactive protein point-of-care tests vs. usual care: pooled risk ratio 0.75, 95% confidence interval 0.68 to 0.84; nine studies). The effects of procalcitonin point-of-care tests compared with usual care on hospital admission, escalation of care, and duration of symptoms were very uncertain as only one randomised controlled trial was included. The study found a large reduction in antibiotic prescriptions within 7 days. Two studies revealed a large reduction in initial antibiotic prescriptions for Group A streptococcus point-of-care tests versus usual care. Only one study compared an influenza point-of-care test with usual care. The effect of the antibiotics prescribed was very uncertain. No deaths occurred in either treatment group.</p><p><strong>Cost-effectiveness: </strong>Six of the 17 included cost-utility studies were judged to be directly applicable to our review, 4 of which focused on the C-reactive protein point-of-care test. The results suggested that the C-reactive protein point-of-care test is potentially cost-effective; these studies were generally limited to capturing only short-term costs and consequences. One study evaluated 14 different point-of-care tests for Group A streptococcus; none were cost-effective compared with usual care. A further study evaluated two rapid tests (","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 13","pages":"1-114"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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