Kevin Cooper, Lynda Constable, Thenmalar Vadiveloo, Ayodeji Matuluko, Christine Kennedy, Sharon McCann, Seonaidh Cotton, Katie Gillies, Rebecca Bruce, Paul Smith, Graeme MacLennan, T Justin Clark
<p><strong>Background: </strong>Deep endometriosis causes significant pain which adversely affects quality of life and utilises healthcare and wider societal resources. Laparoscopic excision of endometriosis has shown to improve pain symptoms in observational series but 1 in 14 patients experience serious surgical complications. Medical management centres around hormonal treatment, which is less risky and has been shown to be efficacious but can cause troublesome side effects and is incompatible with conception. There are no randomised controlled trials providing conclusive comparative evidence on clinical and cost-effectiveness of these treatments.</p><p><strong>Objective(s): </strong>To compare the clinical and cost-effectiveness of laparoscopic surgery versus optimised medical treatment for managing deep endometriosis.</p><p><strong>Design and methods: </strong>A multicentre randomised controlled trial, with an internal pilot phase, and economic evaluation, to compare early planned laparoscopic surgery (first attempt at definitive surgery) with or without adjuvant medical treatment versus optimised medical management alone in women with deep endometriosis.</p><p><strong>Setting and participants: </strong>Women presenting with pelvic pain associated with surgically or radiologically confirmed deep endometriosis, suitable for either surgical or medical management, recruited and managed at accredited British Society for Gynaecological Endoscopy Endometriosis Centres.</p><p><strong>Interventions: </strong>Early planned laparoscopic surgery to excise deep endometriosis (with or without medical treatment) or medical management alone.</p><p><strong>Main outcome measures: </strong>The primary outcome was condition-specific quality of life measured using the pain domain of the Endometriosis Health Profile-30 at 18 months post randomisation. The primary health economic outcome was to be incremental cost per quality-adjusted life-year gained at 18 months. Secondary outcomes included quality of life (Endometriosis Health Profile-30), pain, complications, occupational and reproductive outcomes.</p><p><strong>Results: </strong>Three hundred and seventy-seven patients were screened, 103 were eligible and 18 were randomised. Of the eight patients allocated surgery, only one had had their surgery by the time of trial closure and six participants (2/4, 50% allocated surgery and 4/8, 50% allocated medical treatment) had reached the first trial end point at 3 months. No participant reached the primary outcome at 18 months post randomisation.</p><p><strong>Limitations: </strong>The overriding limitation was failure to recruit participants at a satisfactory rate resulting in a final sample of only 18 patients with a target of 320 (inflated to 400 to account for a projected 20% attrition rate). Given the nature of the intervention, it was not possible to blind either the care providers, investigators or participants to their allocated group.</p><p><strong>Conclusion
{"title":"Clinical and cost-effectiveness of medical management versus surgery for deep infiltrating endometriosis: synopsis from the DIAMOND RCT.","authors":"Kevin Cooper, Lynda Constable, Thenmalar Vadiveloo, Ayodeji Matuluko, Christine Kennedy, Sharon McCann, Seonaidh Cotton, Katie Gillies, Rebecca Bruce, Paul Smith, Graeme MacLennan, T Justin Clark","doi":"10.3310/GJKC5715","DOIUrl":"10.3310/GJKC5715","url":null,"abstract":"<p><strong>Background: </strong>Deep endometriosis causes significant pain which adversely affects quality of life and utilises healthcare and wider societal resources. Laparoscopic excision of endometriosis has shown to improve pain symptoms in observational series but 1 in 14 patients experience serious surgical complications. Medical management centres around hormonal treatment, which is less risky and has been shown to be efficacious but can cause troublesome side effects and is incompatible with conception. There are no randomised controlled trials providing conclusive comparative evidence on clinical and cost-effectiveness of these treatments.</p><p><strong>Objective(s): </strong>To compare the clinical and cost-effectiveness of laparoscopic surgery versus optimised medical treatment for managing deep endometriosis.</p><p><strong>Design and methods: </strong>A multicentre randomised controlled trial, with an internal pilot phase, and economic evaluation, to compare early planned laparoscopic surgery (first attempt at definitive surgery) with or without adjuvant medical treatment versus optimised medical management alone in women with deep endometriosis.</p><p><strong>Setting and participants: </strong>Women presenting with pelvic pain associated with surgically or radiologically confirmed deep endometriosis, suitable for either surgical or medical management, recruited and managed at accredited British Society for Gynaecological Endoscopy Endometriosis Centres.</p><p><strong>Interventions: </strong>Early planned laparoscopic surgery to excise deep endometriosis (with or without medical treatment) or medical management alone.</p><p><strong>Main outcome measures: </strong>The primary outcome was condition-specific quality of life measured using the pain domain of the Endometriosis Health Profile-30 at 18 months post randomisation. The primary health economic outcome was to be incremental cost per quality-adjusted life-year gained at 18 months. Secondary outcomes included quality of life (Endometriosis Health Profile-30), pain, complications, occupational and reproductive outcomes.</p><p><strong>Results: </strong>Three hundred and seventy-seven patients were screened, 103 were eligible and 18 were randomised. Of the eight patients allocated surgery, only one had had their surgery by the time of trial closure and six participants (2/4, 50% allocated surgery and 4/8, 50% allocated medical treatment) had reached the first trial end point at 3 months. No participant reached the primary outcome at 18 months post randomisation.</p><p><strong>Limitations: </strong>The overriding limitation was failure to recruit participants at a satisfactory rate resulting in a final sample of only 18 patients with a target of 320 (inflated to 400 to account for a projected 20% attrition rate). Given the nature of the intervention, it was not possible to blind either the care providers, investigators or participants to their allocated group.</p><p><strong>Conclusion","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-27"},"PeriodicalIF":4.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099599","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}
Gwenllian Wynne-Jones, Martyn Lewis, Gail Sowden, Ira Madan, Karen Walker-Bone, Carolyn A Chew-Graham, Kieran Bromley, Sue Jowett, Vaughan Parsons, Gemma Mansell, Kendra Cooke, Benjamin Saunders, Rosie Harrison, Sarah A Lawton, Simon Wathall, John Pemberton, Julia Hammond, Cyrus Cooper, And Nadine E Foster
Background and objectives: To describe exploratory findings and lessons learned from the discontinued WAVE trial, which sought to determine the effectiveness and costs of adding an early vocational advice intervention to usual primary care on number of days of sickness absence over 6 months.
Methods: Pragmatic, multicentre, two-parallel arm, superiority, randomised controlled trial with health economic analysis in 10 general practices in England, with nested qualitative interviews. Population: Adults with fit notes for any health condition, absent from work ≥ 2 weeks and ≤ 6 months were invited to participate. Intervention and comparator: Participants were randomised (1 : 1) to usual primary care with/without vocational advice delivered by trained Vocational Support Workers. The planned sample size was 720, the first 4 months of recruitment served as an internal pilot phase and the primary outcome was self-reported days of work absence over 6 months.
Results: One hundred and thirty participants were recruited from 7955 invitations (May 2022-May 2023) before trial closure (64 usual care, 66 usual care plus vocational advice). Exploratory analysis of 125 participants (with outcome data) indicated small additional benefits of the vocational advice intervention over usual care [mean days absence = 37.86 (standard deviation = 48.76) vs. usual care = 42.66 (standard deviation = 57.67), incidence rate ratio = 0.913, 80% confidence interval (0.653 to 1.276)]. The vocational advice intervention was delivered remotely [mean = 4.8 contacts (range 1-12)]. Partial health economic evaluation found lower work productivity losses at 6 months after vocational advice intervention (£5513.84, standard deviation = £7101.43) compared to usual care (£6146.21, standard deviation = £8431.88).
Conclusions, limitations and future work: Exploratory analysis indicated a signal of effect, with differences in the number of days absent from work, costs and secondary outcomes. Key lessons learned included the need for closer working with primary care teams and more flexible recruitment methods. A future fully powered randomised controlled trial of vocational advice intervention added to usual primary care is needed to determine the effectiveness and cost-effectiveness.
Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/94/49.
{"title":"Addition of early vocational advice to usual primary care on sickness absence in employed adults: exploratory findings from the discontinued WAVE Randomised Controlled Trial.","authors":"Gwenllian Wynne-Jones, Martyn Lewis, Gail Sowden, Ira Madan, Karen Walker-Bone, Carolyn A Chew-Graham, Kieran Bromley, Sue Jowett, Vaughan Parsons, Gemma Mansell, Kendra Cooke, Benjamin Saunders, Rosie Harrison, Sarah A Lawton, Simon Wathall, John Pemberton, Julia Hammond, Cyrus Cooper, And Nadine E Foster","doi":"10.3310/SVEG8456","DOIUrl":"10.3310/SVEG8456","url":null,"abstract":"<p><strong>Background and objectives: </strong>To describe exploratory findings and lessons learned from the discontinued WAVE trial, which sought to determine the effectiveness and costs of adding an early vocational advice intervention to usual primary care on number of days of sickness absence over 6 months.</p><p><strong>Methods: </strong>Pragmatic, multicentre, two-parallel arm, superiority, randomised controlled trial with health economic analysis in 10 general practices in England, with nested qualitative interviews. Population: Adults with fit notes for any health condition, absent from work ≥ 2 weeks and ≤ 6 months were invited to participate. Intervention and comparator: Participants were randomised (1 : 1) to usual primary care with/without vocational advice delivered by trained Vocational Support Workers. The planned sample size was 720, the first 4 months of recruitment served as an internal pilot phase and the primary outcome was self-reported days of work absence over 6 months.</p><p><strong>Results: </strong>One hundred and thirty participants were recruited from 7955 invitations (May 2022-May 2023) before trial closure (64 usual care, 66 usual care plus vocational advice). Exploratory analysis of 125 participants (with outcome data) indicated small additional benefits of the vocational advice intervention over usual care [mean days absence = 37.86 (standard deviation = 48.76) vs. usual care = 42.66 (standard deviation = 57.67), incidence rate ratio = 0.913, 80% confidence interval (0.653 to 1.276)]. The vocational advice intervention was delivered remotely [mean = 4.8 contacts (range 1-12)]. Partial health economic evaluation found lower work productivity losses at 6 months after vocational advice intervention (£5513.84, standard deviation = £7101.43) compared to usual care (£6146.21, standard deviation = £8431.88).</p><p><strong>Conclusions, limitations and future work: </strong>Exploratory analysis indicated a signal of effect, with differences in the number of days absent from work, costs and secondary outcomes. Key lessons learned included the need for closer working with primary care teams and more flexible recruitment methods. A future fully powered randomised controlled trial of vocational advice intervention added to usual primary care is needed to determine the effectiveness and cost-effectiveness.</p><p><strong>Funding: </strong>This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/94/49.</p>","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-32"},"PeriodicalIF":4.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100155","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, Jacqueline Dinnes, Breanna Morrison, April Coombe, Ridhi Agarwal, Isaac Adu Asare, Phoebe Mead, Andy De Souza, David Elliman, Silvia Lombardo, John Marshall, Sian Taylor-Phillips, Yemisi Takwoingi
<p><strong>Background: </strong>Newborn bloodspot screening offers the potential to detect rare diseases early, enabling timely treatment that can reduce mortality and morbidity. Generating evidence for rare diseases often depends on observational data, making it challenging to formulate recommendations for new screening programmes and evaluate the effectiveness of existing ones.</p><p><strong>Objective(s): </strong>To identify the range of methods and mechanisms used to measure and monitor outcomes from newborn screening programmes using a scoping review.</p><p><strong>Methods: </strong>We included studies published between 2019 and 2024, which evaluated a current or candidate newborn screening programme, or which reported outcomes in screen-detected cases. Studies were categorised into four groups: group 1 reported a comparison and follow-up; group 2 reported a comparison but no follow-up; group 3 reported no comparison with follow-up; and group 4 reported no comparison or follow-up. Data were extracted from a random sample of studies within each group; studies in group 1 were prioritised. Results were reported narratively according to study group. The review was conducted and reported according to current guidance for scoping reviews.</p><p><strong>Data sources: </strong>EMBASE (Ovid), MEDLINE (Ovid) and Science Citation Index (Web of Science - Clarivate).</p><p><strong>Results: </strong>We included 574 primary studies and extracted data from 178. Of the 75 studies in group 1, most compared screen-detected cases with controls (74%). Studies in this group used newborn bloodspot programme databases, registries or record review to identify participants and outcomes; only six (8%) reported use of record linkage. Studies in group 2 (<i>n</i> = 31) mostly reported comparisons of screening tests (25, 81%). Over half of studies in group 3 (<i>n</i> = 34) used newborn bloodspot programme databases to identify participants (53%) and outcomes (65%). A similar pattern was seen in the group 4 (<i>n</i> = 38). Studies reporting follow-up typically relied on retrospective record review or were not well reported. Across all study groups, data on accuracy, epidemiology and genetic variants were common. Studies in group 1 also reported on the effectiveness of newborn bloodspot screening (32/75, 43%), treatment effectiveness (20%) or harms of newborn bloodspot screening (3%).</p><p><strong>Limitations: </strong>Restricting data extraction to a random sample of studies risks missing novel methods or mechanisms.</p><p><strong>Conclusions: </strong>Many studies reported test accuracy metrics and genetic variants in newborn screening. Some data on programme effectiveness were identified, but assessment of potential harms remains limited, and methods for follow-up were poorly reported. Assessment of harms, including overdiagnosis and psychological impact, is crucial to ensuring a net benefit at the population level.</p><p><strong>Future work: </strong>In a second pha
背景：新生儿血斑筛查提供了早期发现罕见疾病的潜力，使及时治疗能够降低死亡率和发病率。为罕见病提供证据往往依赖于观察数据，因此很难为新的筛查方案提出建议，也很难评估现有方案的有效性。目的：通过范围审查确定用于测量和监测新生儿筛查项目结果的方法和机制的范围。方法：我们纳入了2019年至2024年间发表的研究，这些研究评估了当前或候选的新生儿筛查项目，或报告了筛查检测病例的结果。研究分为四组：第一组报告了比较和随访；第二组报告了比较，但没有随访；第三组无随访比较；第4组没有进行比较或随访。数据从每组的随机研究样本中提取；第一组的研究被优先考虑。结果按研究组分组记叙。审查是根据当前范围审查指南进行和报告的。数据来源：EMBASE (Ovid), MEDLINE （Ovid）和Science Citation Index （Web of Science - Clarivate）。结果：我们纳入了574项初步研究，提取了178项数据。在第一组的75项研究中，大多数将筛查检测到的病例与对照组进行比较（74%）。该组研究使用新生儿血斑规划数据库、登记处或记录审查来确定参与者和结果；只有6个（8%）报告使用了记录链接。第2组（n = 31）的研究大多报告了筛查试验的比较（25.81%）。第3组中超过一半的研究（n = 34）使用新生儿血斑规划数据库来确定参与者（53%）和结果（65%）。第4组（n = 38）也出现了类似的情况。报告随访的研究通常依赖于回顾性记录审查或没有得到很好的报道。在所有研究组中，准确性、流行病学和遗传变异的数据都很常见。第1组的研究还报告了新生儿血斑筛查的有效性（32/ 75,43 %）、治疗有效性（20%）或新生儿血斑筛查的危害（3%）。局限性：将数据提取限制在随机的研究样本中，可能会错过新的方法或机制。结论：许多研究报告了新生儿筛查的测试准确性指标和遗传变异。确定了一些关于方案有效性的数据，但对潜在危害的评估仍然有限，后续行动的方法报告也很差。评估危害，包括过度诊断和心理影响，对于确保在人口层面上获得净效益至关重要。未来的工作：在第二阶段的工作中，将对使用不同方法和机制的研究进行深入评估，以确定它们可以提供结果数据的程度，从而为正在进行的和候选筛选计划的评估提供信息。资助：本文介绍了由国家卫生与保健研究所（NIHR）卫生技术评估计划资助的独立研究，奖励号为NIHR167910。
{"title":"Methods and mechanisms for measuring and monitoring outcomes from newborn bloodspot screening: a scoping review.","authors":"Katie Scandrett, Jacqueline Dinnes, Breanna Morrison, April Coombe, Ridhi Agarwal, Isaac Adu Asare, Phoebe Mead, Andy De Souza, David Elliman, Silvia Lombardo, John Marshall, Sian Taylor-Phillips, Yemisi Takwoingi","doi":"10.3310/GJJD1717","DOIUrl":"10.3310/GJJD1717","url":null,"abstract":"<p><strong>Background: </strong>Newborn bloodspot screening offers the potential to detect rare diseases early, enabling timely treatment that can reduce mortality and morbidity. Generating evidence for rare diseases often depends on observational data, making it challenging to formulate recommendations for new screening programmes and evaluate the effectiveness of existing ones.</p><p><strong>Objective(s): </strong>To identify the range of methods and mechanisms used to measure and monitor outcomes from newborn screening programmes using a scoping review.</p><p><strong>Methods: </strong>We included studies published between 2019 and 2024, which evaluated a current or candidate newborn screening programme, or which reported outcomes in screen-detected cases. Studies were categorised into four groups: group 1 reported a comparison and follow-up; group 2 reported a comparison but no follow-up; group 3 reported no comparison with follow-up; and group 4 reported no comparison or follow-up. Data were extracted from a random sample of studies within each group; studies in group 1 were prioritised. Results were reported narratively according to study group. The review was conducted and reported according to current guidance for scoping reviews.</p><p><strong>Data sources: </strong>EMBASE (Ovid), MEDLINE (Ovid) and Science Citation Index (Web of Science - Clarivate).</p><p><strong>Results: </strong>We included 574 primary studies and extracted data from 178. Of the 75 studies in group 1, most compared screen-detected cases with controls (74%). Studies in this group used newborn bloodspot programme databases, registries or record review to identify participants and outcomes; only six (8%) reported use of record linkage. Studies in group 2 (<i>n</i> = 31) mostly reported comparisons of screening tests (25, 81%). Over half of studies in group 3 (<i>n</i> = 34) used newborn bloodspot programme databases to identify participants (53%) and outcomes (65%). A similar pattern was seen in the group 4 (<i>n</i> = 38). Studies reporting follow-up typically relied on retrospective record review or were not well reported. Across all study groups, data on accuracy, epidemiology and genetic variants were common. Studies in group 1 also reported on the effectiveness of newborn bloodspot screening (32/75, 43%), treatment effectiveness (20%) or harms of newborn bloodspot screening (3%).</p><p><strong>Limitations: </strong>Restricting data extraction to a random sample of studies risks missing novel methods or mechanisms.</p><p><strong>Conclusions: </strong>Many studies reported test accuracy metrics and genetic variants in newborn screening. Some data on programme effectiveness were identified, but assessment of potential harms remains limited, and methods for follow-up were poorly reported. Assessment of harms, including overdiagnosis and psychological impact, is crucial to ensuring a net benefit at the population level.</p><p><strong>Future work: </strong>In a second pha","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-48"},"PeriodicalIF":4.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12862532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046461","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}
Timothy S Walsh, Richard A Parker, Leanne M Aitken, Cathrine A McKenzie, Robert Glen, Christopher J Weir
<p><strong>Background: </strong>Optimising comfort and ability to communicate for mechanically ventilated intensive care unit patients is a priority for clinicians, intensive care unit patients and their relatives. Current usual care is propofol-based sedation plus an opioid analgesic. The alpha2-agonists dexmedetomidine and clonidine are potential alternative sedatives.</p><p><strong>Objective(s): </strong>To explore whether nurses and relatives perceive patients sedated with dexmedetomidine and/or clonidine appear more awake, comfortable and co-operative than patients receiving only propofol-based sedation.</p><p><strong>Design and methods: </strong>Substudy within an open-label, three-arm trial.</p><p><strong>Setting and participants: </strong>Forty-one intensive care units in the United Kingdom. One thousand four hundred and thirty-seven adults receiving propofol ± opioid for sedation-analgesia within 48 hours of starting mechanical ventilation, expected to require ≥ 48 total hours of mechanical ventilation.</p><p><strong>Interventions: </strong>Light sedation was targeted in all patients unless clinicians requested deeper sedation. In intervention groups, algorithms promoted alpha2-agonist up-titration and propofol down-titration, followed by sedation primarily with allocated alpha2-agonist. Usual care was propofol-based sedation. Intervention continued until patients were successfully extubated (primary outcome), or other pre-defined end points.</p><p><strong>Outcomes: </strong>For each 12-hour care period, nurses responded to two 'yes/no' questions: <i>is the patient able to communicate pain? Is the patient able to co-operate with care?</i> When the patients' personal legal representative visited, they were asked for 'yes/no' responses to three questions: <i>does the patient appear awake? Does the patient appear comfortable? Does the visitor feel they can communicate with the patient?</i> Intervention versus propofol group responses were compared fitting a generalised linear mixed model, with results expressed as odds ratios (95% confidence intervals); odds ratios > 1 indicated greater probability of a 'yes' response.</p><p><strong>Results: </strong>Nurse responses were available for > 90% of trial patients [mean (standard deviation) 12 (12) care periods per patient]. Comparing dexmedetomidine versus propofol groups, the odds ratio for a 'yes' response to '<i>communicate pain</i>' was 1.38 (95% confidence interval 1.08 to 1.75), and for clonidine versus propofol, it was 1.13 (0.89 to 1.43). For '<i>co-operate with care</i>' comparing dexmedetomidine versus propofol groups, the odds ratio was 1.14 (95% confidence interval 0.98 to 1.32), and for clonidine versus propofol, it was 0.96 (95% confidence interval 0.83 to 1.12). Relative responses were available for 32-34% of trial patients across groups [mean (standard deviation) 3 (3) days per patient]. For the '<i>appear awake</i>' question, the dexmedetomidine versus propofol group odds ratio
{"title":"Relative and bedside nurse assessment of comfort and communication during propofol, dexmedetomidine, or clonidine-based sedation: pre-planned analysis within the A2B RCT.","authors":"Timothy S Walsh, Richard A Parker, Leanne M Aitken, Cathrine A McKenzie, Robert Glen, Christopher J Weir","doi":"10.3310/GJTW2718","DOIUrl":"10.3310/GJTW2718","url":null,"abstract":"<p><strong>Background: </strong>Optimising comfort and ability to communicate for mechanically ventilated intensive care unit patients is a priority for clinicians, intensive care unit patients and their relatives. Current usual care is propofol-based sedation plus an opioid analgesic. The alpha2-agonists dexmedetomidine and clonidine are potential alternative sedatives.</p><p><strong>Objective(s): </strong>To explore whether nurses and relatives perceive patients sedated with dexmedetomidine and/or clonidine appear more awake, comfortable and co-operative than patients receiving only propofol-based sedation.</p><p><strong>Design and methods: </strong>Substudy within an open-label, three-arm trial.</p><p><strong>Setting and participants: </strong>Forty-one intensive care units in the United Kingdom. One thousand four hundred and thirty-seven adults receiving propofol ± opioid for sedation-analgesia within 48 hours of starting mechanical ventilation, expected to require ≥ 48 total hours of mechanical ventilation.</p><p><strong>Interventions: </strong>Light sedation was targeted in all patients unless clinicians requested deeper sedation. In intervention groups, algorithms promoted alpha2-agonist up-titration and propofol down-titration, followed by sedation primarily with allocated alpha2-agonist. Usual care was propofol-based sedation. Intervention continued until patients were successfully extubated (primary outcome), or other pre-defined end points.</p><p><strong>Outcomes: </strong>For each 12-hour care period, nurses responded to two 'yes/no' questions: <i>is the patient able to communicate pain? Is the patient able to co-operate with care?</i> When the patients' personal legal representative visited, they were asked for 'yes/no' responses to three questions: <i>does the patient appear awake? Does the patient appear comfortable? Does the visitor feel they can communicate with the patient?</i> Intervention versus propofol group responses were compared fitting a generalised linear mixed model, with results expressed as odds ratios (95% confidence intervals); odds ratios > 1 indicated greater probability of a 'yes' response.</p><p><strong>Results: </strong>Nurse responses were available for > 90% of trial patients [mean (standard deviation) 12 (12) care periods per patient]. Comparing dexmedetomidine versus propofol groups, the odds ratio for a 'yes' response to '<i>communicate pain</i>' was 1.38 (95% confidence interval 1.08 to 1.75), and for clonidine versus propofol, it was 1.13 (0.89 to 1.43). For '<i>co-operate with care</i>' comparing dexmedetomidine versus propofol groups, the odds ratio was 1.14 (95% confidence interval 0.98 to 1.32), and for clonidine versus propofol, it was 0.96 (95% confidence interval 0.83 to 1.12). Relative responses were available for 32-34% of trial patients across groups [mean (standard deviation) 3 (3) days per patient]. For the '<i>appear awake</i>' question, the dexmedetomidine versus propofol group odds ratio ","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-18"},"PeriodicalIF":4.0,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12862536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997903","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}
Dawn Lee, Madhusubramanian Muthukumar, Alan Lovell, Caroline Farmer, Darren Burns, Justin Matthews, Helen Coelho, Brian O'Toole, Laura A Trigg, Tristan M Snowsill, Maxwell S Barnish, Thalia Nikoglou, Amanda Brand, Zain Ahmad, Ahmed Abdelsabour, Louise Crathorne, Sophie Robinson, Edward Cf Wilson, G J Melendez-Torres
<p><strong>Background: </strong>The National Institute for Health and Care Excellence is piloting a new approach to evaluating health technologies, which takes into consideration the full treatment pathway for a condition. This report describes the first pilot topic for the pathways process, which evaluated systemic treatments for advanced renal cell carcinoma.</p><p><strong>Objectives: </strong>This pilot aimed to develop a decision model representing the treatment pathway that will be used to evaluate new technologies for advanced renal cell carcinoma. The pilot also evaluated a new treatment for renal cell carcinoma: cabozantinib (Cabometyx®; Ipsen, Slough, UK) plus nivolumab (Opdivo®; Bristol Myers Squibb, Princeton, NJ, USA).</p><p><strong>Review methods: </strong>A systematic literature review was conducted to identify evidence to inform effectiveness, safety and economic model development, including systematic literature reviews, randomised controlled trials, economic evaluations, utility studies and cost and resource use data. Real-world evidence was sought following the recommendations of the National Institute for Health and Care Excellence real-world evidence framework. Structured expert elicitation informed assumptions about overall survival and progression-free survival. Network meta-analyses were conducted to evaluate the clinical effectiveness of treatments. A de novo state transition model that was constructed with a partitioned survival analysis structure was also presented. The cost perspective of the model was that of the National Health Service and Personal Social Services; the time horizon was 40 years, costs and outcomes were discounted at 3.5% per annum and a 2022 price year was used. The model allowed sequences of up to four active lines of treatment.</p><p><strong>Information sources: </strong>The review included 118 systematic literature reviews, 30 randomised controlled trials, 122 economic evaluations, 82 studies reporting utility data and 13 studies reporting cost and/or resource use data. A total of 21 real-world evidence sources were identified. Unpublished data were provided by the manufacturer and other stakeholders (competitor companies, patient and clinical organisations). The expert elicitation recruited nine United Kingdom-based oncologists.</p><p><strong>Results: </strong>Cabozantinib plus nivolumab was associated with better progression-free survival and overall survival than existing tyrosine kinase inhibitors as first-line treatment in the all-risk group. Using the list price of the evaluated interventions, the incremental cost-effectiveness ratio for cabozantinib plus nivolumab compared to the next non-dominated tyrosine kinase inhibitor monotherapy (pazopanib [Votrient®; Novartis, Slough, UK]) was £275,106 per quality-adjusted life-year in the all-risk population and was £379,222 in the favourable-risk population. Incremental cost-effectiveness ratios were relatively consistent across the base-case and s
{"title":"Treatments for renal cell carcinoma: NICE Pilot Treatment Pathways Appraisal.","authors":"Dawn Lee, Madhusubramanian Muthukumar, Alan Lovell, Caroline Farmer, Darren Burns, Justin Matthews, Helen Coelho, Brian O'Toole, Laura A Trigg, Tristan M Snowsill, Maxwell S Barnish, Thalia Nikoglou, Amanda Brand, Zain Ahmad, Ahmed Abdelsabour, Louise Crathorne, Sophie Robinson, Edward Cf Wilson, G J Melendez-Torres","doi":"10.3310/GJDL0327","DOIUrl":"10.3310/GJDL0327","url":null,"abstract":"<p><strong>Background: </strong>The National Institute for Health and Care Excellence is piloting a new approach to evaluating health technologies, which takes into consideration the full treatment pathway for a condition. This report describes the first pilot topic for the pathways process, which evaluated systemic treatments for advanced renal cell carcinoma.</p><p><strong>Objectives: </strong>This pilot aimed to develop a decision model representing the treatment pathway that will be used to evaluate new technologies for advanced renal cell carcinoma. The pilot also evaluated a new treatment for renal cell carcinoma: cabozantinib (Cabometyx®; Ipsen, Slough, UK) plus nivolumab (Opdivo®; Bristol Myers Squibb, Princeton, NJ, USA).</p><p><strong>Review methods: </strong>A systematic literature review was conducted to identify evidence to inform effectiveness, safety and economic model development, including systematic literature reviews, randomised controlled trials, economic evaluations, utility studies and cost and resource use data. Real-world evidence was sought following the recommendations of the National Institute for Health and Care Excellence real-world evidence framework. Structured expert elicitation informed assumptions about overall survival and progression-free survival. Network meta-analyses were conducted to evaluate the clinical effectiveness of treatments. A de novo state transition model that was constructed with a partitioned survival analysis structure was also presented. The cost perspective of the model was that of the National Health Service and Personal Social Services; the time horizon was 40 years, costs and outcomes were discounted at 3.5% per annum and a 2022 price year was used. The model allowed sequences of up to four active lines of treatment.</p><p><strong>Information sources: </strong>The review included 118 systematic literature reviews, 30 randomised controlled trials, 122 economic evaluations, 82 studies reporting utility data and 13 studies reporting cost and/or resource use data. A total of 21 real-world evidence sources were identified. Unpublished data were provided by the manufacturer and other stakeholders (competitor companies, patient and clinical organisations). The expert elicitation recruited nine United Kingdom-based oncologists.</p><p><strong>Results: </strong>Cabozantinib plus nivolumab was associated with better progression-free survival and overall survival than existing tyrosine kinase inhibitors as first-line treatment in the all-risk group. Using the list price of the evaluated interventions, the incremental cost-effectiveness ratio for cabozantinib plus nivolumab compared to the next non-dominated tyrosine kinase inhibitor monotherapy (pazopanib [Votrient®; Novartis, Slough, UK]) was £275,106 per quality-adjusted life-year in the all-risk population and was £379,222 in the favourable-risk population. Incremental cost-effectiveness ratios were relatively consistent across the base-case and s","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 1","pages":"1-221"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12833715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003346","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}
Matthew Prescott, Michelle Collinson, Abi J Hall, Rebecca Bestwick, Victoria A Goodwin, Ellen Thompson, Chris Bojke, David Clarke, Florence Day, Anne Forster, Claire Hulme, Julie Peacock, Friederike Ziegler, Amanda J Farrin, Andrew Clegg
<p><strong>Background: </strong>Half of older people in hospital have frailty and are at increased risk of re-admission or death following discharge. Although short-term rehabilitation can reduce early re-admissions, benefits are attenuated over time. It is unknown whether extended rehabilitation for older people with frailty can improve outcomes.</p><p><strong>Trial design: </strong>Pragmatic, multicentre, individually randomised controlled parallel-group superiority trial with economic evaluation and embedded process evaluation.</p><p><strong>Methods: </strong>Participants: Eligible participants were 65 years or older with mild/moderate/severe frailty (score of 5-7 on Clinical Frailty Scale) admitted to hospital with acute illness or injury, then discharged home directly or from intermediate care (post-acute care) rehabilitation services. People with significant cognitive impairment and care home residents were among those ineligible. Recruitment took place from December 2017 to August 2021, with follow-up till August 2022. Interventions: Participants were randomly assigned (1.28 : 1) to the Home-based Older People's Exercise programme - a 24-week home-based manualised, progressive exercise intervention delivered by National Health Service therapists as extended rehabilitation, or usual care (control). Randomisation occurred after the participant had been discharged from hospital or intermediate care. Participants were not masked to allocation. Main outcome measures: The primary outcome was physical health-related quality of life, measured using the physical component score of the modified Short Form 36-item health questionnaire at 12 months. Secondary outcomes at 6 and 12 months included physical and mental health-related quality of life, functional independence, death, hospitalisations and care home admissions. Researchers involved in data collection were masked to allocation. Data sources: Primary and secondary outcomes were obtained via self-report questionnaire at 6 and 12 months. Hospitalisations and deaths were collected from routine healthcare data.</p><p><strong>Results: </strong>We randomised 740 participants (410 Home-based Older People's Exercise, 330 control) across 15 sites. Four hundred and seventy-nine (64.7%) participants completed 12-month follow-up. One hundred and eighty-eight Home-based Older People's Exercise participants (45.9%) completed 24 weeks of intervention delivery. Over half of participants completed more than 75% of prescribed exercises. Intention-to-treat analyses (258 Home-based Older People's Exercise participants, 208 control participants for primary outcome) showed no evidence that Home-based Older People's Exercise was superior to control for 12-month physical component score (adjusted mean difference -0.22, 95% confidence interval -1.47 to 1.03; <i>p</i> = 0.73). There was some evidence of a higher rate of all-cause hospitalisations in the control arm (incidence rate ratio 1.12, 95% confidence interval 1.0
{"title":"Home-based extended rehabilitation for older people with frailty (HERO): a multicentre randomised controlled trial with health economic analysis and process evaluation.","authors":"Matthew Prescott, Michelle Collinson, Abi J Hall, Rebecca Bestwick, Victoria A Goodwin, Ellen Thompson, Chris Bojke, David Clarke, Florence Day, Anne Forster, Claire Hulme, Julie Peacock, Friederike Ziegler, Amanda J Farrin, Andrew Clegg","doi":"10.3310/GJAC1602","DOIUrl":"10.3310/GJAC1602","url":null,"abstract":"<p><strong>Background: </strong>Half of older people in hospital have frailty and are at increased risk of re-admission or death following discharge. Although short-term rehabilitation can reduce early re-admissions, benefits are attenuated over time. It is unknown whether extended rehabilitation for older people with frailty can improve outcomes.</p><p><strong>Trial design: </strong>Pragmatic, multicentre, individually randomised controlled parallel-group superiority trial with economic evaluation and embedded process evaluation.</p><p><strong>Methods: </strong>Participants: Eligible participants were 65 years or older with mild/moderate/severe frailty (score of 5-7 on Clinical Frailty Scale) admitted to hospital with acute illness or injury, then discharged home directly or from intermediate care (post-acute care) rehabilitation services. People with significant cognitive impairment and care home residents were among those ineligible. Recruitment took place from December 2017 to August 2021, with follow-up till August 2022. Interventions: Participants were randomly assigned (1.28 : 1) to the Home-based Older People's Exercise programme - a 24-week home-based manualised, progressive exercise intervention delivered by National Health Service therapists as extended rehabilitation, or usual care (control). Randomisation occurred after the participant had been discharged from hospital or intermediate care. Participants were not masked to allocation. Main outcome measures: The primary outcome was physical health-related quality of life, measured using the physical component score of the modified Short Form 36-item health questionnaire at 12 months. Secondary outcomes at 6 and 12 months included physical and mental health-related quality of life, functional independence, death, hospitalisations and care home admissions. Researchers involved in data collection were masked to allocation. Data sources: Primary and secondary outcomes were obtained via self-report questionnaire at 6 and 12 months. Hospitalisations and deaths were collected from routine healthcare data.</p><p><strong>Results: </strong>We randomised 740 participants (410 Home-based Older People's Exercise, 330 control) across 15 sites. Four hundred and seventy-nine (64.7%) participants completed 12-month follow-up. One hundred and eighty-eight Home-based Older People's Exercise participants (45.9%) completed 24 weeks of intervention delivery. Over half of participants completed more than 75% of prescribed exercises. Intention-to-treat analyses (258 Home-based Older People's Exercise participants, 208 control participants for primary outcome) showed no evidence that Home-based Older People's Exercise was superior to control for 12-month physical component score (adjusted mean difference -0.22, 95% confidence interval -1.47 to 1.03; <i>p</i> = 0.73). There was some evidence of a higher rate of all-cause hospitalisations in the control arm (incidence rate ratio 1.12, 95% confidence interval 1.0","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 4","pages":"1-40"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12833716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010043","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}
<p><strong>Background: </strong>Bariatric surgery can improve health outcomes but high-quality comparative evidence about different procedures is limited.</p><p><strong>Objective: </strong>To compare the effectiveness and cost-effectiveness of Roux-en-Y gastric bypass (Bypass), adjustable gastric banding (Band) and sleeve gastrectomy (Sleeve) for people living with severe obesity.</p><p><strong>Design, setting and participants: </strong>Multicentre, parallel-group, randomised controlled trial conducted in 12 National Health Service hospitals. Adults with a body mass index ≥ 35 kg/m<sup>2</sup> with comorbidity or body mass index ≥ 40 kg/m<sup>2</sup> without comorbidity were eligible. Participants were initially randomised 1 : 1 to Bypass or Band. After 32 months of recruitment, the trial was adapted to include Sleeve, and participants were randomised to Bypass, Band or Sleeve thereafter. Participants were followed up for 3 years.</p><p><strong>Interventions: </strong>Bypass, Band and Sleeve surgery.</p><p><strong>Main outcome measures: </strong>Primary outcomes were self-reported quality of life (EQ-5D-5L utility score) and weight (at least 50% excess weight lost) at 3 years. Sleeve and Bypass were each considered superior to Band if there was non-inferior excess weight loss (< 12% difference between groups) and superior quality of life. Sleeve was considered superior to Bypass by the same criteria. Secondary outcomes included comorbidities, adverse health events, generic and disease-specific quality of life at 6, 12, 24 and 36 months post randomisation, dietary intake, binge eating behaviour and cost-effectiveness.</p><p><strong>Results: </strong>One thousand three hundred and fifty-one participants were randomised between December 2012 and September 2019. Five participants withdrew consent to use their data, leaving 1346 (462 Bypass, 464 Band, 420 Sleeve). The mean age was 47.3 years, 1020 (75.9%) were women and the mean weight and body mass index was 129.7 kg and 46.4 kg/m<sup>2</sup>, respectively. Overall, 1183 (87.5%) of participants underwent surgery within 3 years, with a median waiting time of 5 months (interquartile range 2.5-10.1 months). At least 50% excess weight loss at 3 years was achieved for 276/405 (68.1%) participants randomised to Bypass, 97/383 (25.3%) randomised to Band and 142/342 (41.5%) randomised to Sleeve [adjusted risk difference (Bypass-Band) + 40.7%, 98% confidence interval (+ 33.9% to + 47.5%); (Sleeve-Band) + 14.7% (+ 5.2% to + 24.2%), (Sleeve-Bypass) -26.0% (-35.8% to -16.3%)]. Mean EQ-5D scores at 3 years were 0.72 (standard deviation 0.29), 0.62 (0.33) and 0.68 (0.30) for participants randomised to Bypass, Band and Sleeve, respectively [adjusted mean difference (Bypass-Band) + 0.079 (+ 0.040 to + 0.117), (Sleeve-Band) + 0.045 (+ 0.006 to + 0.085), (Sleeve-Bypass) -0.033 (-0.072 to + 0.006)]. Secondary outcomes showed similar trends. The adverse event rate was highest in the Band group and lowest with Sleeve. By
{"title":"Roux-en-Y gastric bypass, adjustable gastric banding or sleeve gastrectomy for severe obesity: The By-Band-Sleeve randomised controlled trial.","authors":"","doi":"10.3310/CXSE2951","DOIUrl":"10.3310/CXSE2951","url":null,"abstract":"<p><strong>Background: </strong>Bariatric surgery can improve health outcomes but high-quality comparative evidence about different procedures is limited.</p><p><strong>Objective: </strong>To compare the effectiveness and cost-effectiveness of Roux-en-Y gastric bypass (Bypass), adjustable gastric banding (Band) and sleeve gastrectomy (Sleeve) for people living with severe obesity.</p><p><strong>Design, setting and participants: </strong>Multicentre, parallel-group, randomised controlled trial conducted in 12 National Health Service hospitals. Adults with a body mass index ≥ 35 kg/m<sup>2</sup> with comorbidity or body mass index ≥ 40 kg/m<sup>2</sup> without comorbidity were eligible. Participants were initially randomised 1 : 1 to Bypass or Band. After 32 months of recruitment, the trial was adapted to include Sleeve, and participants were randomised to Bypass, Band or Sleeve thereafter. Participants were followed up for 3 years.</p><p><strong>Interventions: </strong>Bypass, Band and Sleeve surgery.</p><p><strong>Main outcome measures: </strong>Primary outcomes were self-reported quality of life (EQ-5D-5L utility score) and weight (at least 50% excess weight lost) at 3 years. Sleeve and Bypass were each considered superior to Band if there was non-inferior excess weight loss (< 12% difference between groups) and superior quality of life. Sleeve was considered superior to Bypass by the same criteria. Secondary outcomes included comorbidities, adverse health events, generic and disease-specific quality of life at 6, 12, 24 and 36 months post randomisation, dietary intake, binge eating behaviour and cost-effectiveness.</p><p><strong>Results: </strong>One thousand three hundred and fifty-one participants were randomised between December 2012 and September 2019. Five participants withdrew consent to use their data, leaving 1346 (462 Bypass, 464 Band, 420 Sleeve). The mean age was 47.3 years, 1020 (75.9%) were women and the mean weight and body mass index was 129.7 kg and 46.4 kg/m<sup>2</sup>, respectively. Overall, 1183 (87.5%) of participants underwent surgery within 3 years, with a median waiting time of 5 months (interquartile range 2.5-10.1 months). At least 50% excess weight loss at 3 years was achieved for 276/405 (68.1%) participants randomised to Bypass, 97/383 (25.3%) randomised to Band and 142/342 (41.5%) randomised to Sleeve [adjusted risk difference (Bypass-Band) + 40.7%, 98% confidence interval (+ 33.9% to + 47.5%); (Sleeve-Band) + 14.7% (+ 5.2% to + 24.2%), (Sleeve-Bypass) -26.0% (-35.8% to -16.3%)]. Mean EQ-5D scores at 3 years were 0.72 (standard deviation 0.29), 0.62 (0.33) and 0.68 (0.30) for participants randomised to Bypass, Band and Sleeve, respectively [adjusted mean difference (Bypass-Band) + 0.079 (+ 0.040 to + 0.117), (Sleeve-Band) + 0.045 (+ 0.006 to + 0.085), (Sleeve-Bypass) -0.033 (-0.072 to + 0.006)]. Secondary outcomes showed similar trends. The adverse event rate was highest in the Band group and lowest with Sleeve. By","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 6","pages":"1-224"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113041","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}
Dwayne Boyers, Moira Cruickshank, Mohammad Azharuddin, Paul Manson, Diane Swallow, Carl Counsell, Miriam Brazzelli
<p><strong>Background: </strong>Chronic tic disorders and Tourette syndrome typically present around age 5, with peak severity between ages 10 and 12. Treatment approaches vary by country and service availability and include psychoeducation, behavioural therapy, pharmacological therapies and deep brain stimulation. Digitally enabled interventions may improve outcomes.</p><p><strong>Objectives: </strong>We evaluate the clinical and cost-effectiveness of two digital technologies, Online Remote Behavioural Treatment for Tics and Neupulse and identify evidence gaps for future research.</p><p><strong>Methods: </strong>We searched major electronic databases (MEDLINE, EMBASE, Cochrane Library, Web of Science, and Cumulative Index to Nursing and Allied Health Literature) for published studies on clinical and cost-effectiveness. Data were extracted, assessed for bias using Cochrane risk-of-bias tool (version 2), and pooled using random-effects meta-analysis where appropriate. Cost-effectiveness was evaluated using a Markov cohort model with five tic severity states based on the Yale Global Tic Severity Scale - Total Tic Severity Score scale, from a United Kingdom National Health Service perspective. Model inputs were obtained from the Online Remote Behavioural Treatment for Tics study, company data, expert opinion and additional literature.</p><p><strong>Results: </strong>We identified three trials reported across 14 publications: 2 comparing Online Remote Behavioural Treatment for Tics with online psychoeducation, and 1 comparing Neupulse with sham stimulation and a waitlist control. All were assessed as low risk of bias. Meta-analysis of the 2 Online Remote Behavioural Treatment for Tics studies (445 participants) showed significantly lower Yale Global Tic Severity Scale - Total Tic Severity Score at 3 and 12 months compared to online psychoeducation. Results of secondary outcomes were mixed. Neupulse showed significantly lower Yale Global Tic Severity Scale - Total Tic Severity Score, and improvements in motor and phonic tic scores at 4 weeks compared to sham, but no differences in Yale Global Tic Severity Scale-Impairment or Premonitory Urge for Tics Scale - Revised scores. A definitive base-case incremental cost-effectiveness ratio could not be determined due to limited long-term data and uncertainty around long-term combinations of effectiveness and intervention costs in United Kingdom National Health Service practice. Probabilistic incremental cost-effectiveness ratios ranged from £642 per quality-adjusted life-year gained to Online Remote Behavioural Treatment for Tics being dominated. The probability of Online Remote Behavioural Treatment for Tics being cost-effective at a threshold value of £20,000 per quality-adjusted life-year ranged from 52% to 89% across a range of scenarios. Cost-effectiveness results for Neupulse were even more uncertain due to a lack of published data, only a 4-week follow-up and uncertainty surrounding the intervention c
背景：慢性抽动障碍和抽动秽语综合征通常出现在5岁左右，严重程度在10 - 12岁之间达到高峰。治疗方法因国家和服务的可得性而异，包括心理教育、行为治疗、药物治疗和深部脑刺激。数字化干预可以改善结果。目的：我们评估两种数字技术的临床和成本效益，抽搐和神经脉冲的在线远程行为治疗，并为未来的研究确定证据差距。方法：我们检索了主要的电子数据库（MEDLINE， EMBASE, Cochrane Library, Web of Science, and Cumulative Index to Nursing and Allied Health Literature），以获取已发表的临床和成本效益方面的研究。提取数据，使用Cochrane风险-偏倚工具（版本2）评估偏倚，并在适当情况下使用随机效应荟萃分析进行汇总。成本-效果评估采用基于耶鲁全球抽动严重程度量表-总抽动严重程度评分量表的马尔可夫队列模型，从英国国家卫生服务的角度出发。模型输入来自tic在线远程行为治疗研究、公司数据、专家意见和其他文献。结果：我们确定了14份出版物中报道的3项试验：2项比较抽搐症的在线远程行为治疗与在线心理教育，1项比较神经脉冲与假刺激和候补对照。所有被评估为低偏倚风险。对两项抽动症在线远程行为治疗研究（445名参与者）的荟萃分析显示，与在线心理教育相比，3个月和12个月的耶鲁全球抽动症严重程度量表-总抽动症严重程度评分显着降低。次要结局的结果是混合的。与假手术相比，新脉冲手术在4周时的运动和语音抽动评分明显降低，但在耶鲁全球抽动严重程度量表-缺陷或抽动先兆冲动量表-修订评分方面没有差异。由于长期数据有限以及联合王国国民保健服务实践中有效性和干预成本长期组合的不确定性，无法确定确定的基本情况增量成本效益比。概率增量成本效益比从每质量调整生命年获得642英镑到抽动症的在线远程行为治疗占主导地位。在各种情况下，抽搐症在线远程行为治疗在每个质量调整生命年2万英镑的阈值下具有成本效益的可能性在52%到89%之间。由于缺乏公开的数据，只有4周的随访，以及干预成本的不确定性，nepulse的成本效益结果更加不确定。局限性：抽搐和神经性搏动的在线远程行为治疗证据有限，评估结果不一致。比较方法不包括面对面的行为治疗，也不可能区分在线提供的效果与接触和反应预防的效果。由于缺乏长期数据，成本效益结果不确定。结论：抽动症的在线远程行为治疗和神经脉冲治疗似乎都能显著降低耶鲁全球抽动严重程度量表-总抽动严重程度评分，但耶鲁全球抽动严重程度量表-损伤评分没有改善，其他次要结局的结果也不一致，这意味着抽动严重程度评分的改善在多大程度上可以转化为生活质量的改善尚不清楚。由于缺乏长期证据，成本效益估计极不确定。未来研究：需要进行重复性研究来证实研究结果。长期随访——特别是对nepulse的随访——对于了解持续效果和长期成本效益至关重要。更多关于抽动症严重程度的自然过程和治疗效果的可持续性的数据将减少经济模型中的不确定性。未来的研究还应优先考虑反映现实生活对人们日常功能影响的结果。研究注册：本研究注册号为PROSPERO CRD42024508045。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：NIHR136022）资助，全文发表在《卫生技术评估》上；第30卷第8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":"Digitally enabled therapy for chronic tic disorders and Tourette Syndrome: a systematic review and economic evaluation.","authors":"Dwayne Boyers, Moira Cruickshank, Mohammad Azharuddin, Paul Manson, Diane Swallow, Carl Counsell, Miriam Brazzelli","doi":"10.3310/QLAS8524","DOIUrl":"10.3310/QLAS8524","url":null,"abstract":"<p><strong>Background: </strong>Chronic tic disorders and Tourette syndrome typically present around age 5, with peak severity between ages 10 and 12. Treatment approaches vary by country and service availability and include psychoeducation, behavioural therapy, pharmacological therapies and deep brain stimulation. Digitally enabled interventions may improve outcomes.</p><p><strong>Objectives: </strong>We evaluate the clinical and cost-effectiveness of two digital technologies, Online Remote Behavioural Treatment for Tics and Neupulse and identify evidence gaps for future research.</p><p><strong>Methods: </strong>We searched major electronic databases (MEDLINE, EMBASE, Cochrane Library, Web of Science, and Cumulative Index to Nursing and Allied Health Literature) for published studies on clinical and cost-effectiveness. Data were extracted, assessed for bias using Cochrane risk-of-bias tool (version 2), and pooled using random-effects meta-analysis where appropriate. Cost-effectiveness was evaluated using a Markov cohort model with five tic severity states based on the Yale Global Tic Severity Scale - Total Tic Severity Score scale, from a United Kingdom National Health Service perspective. Model inputs were obtained from the Online Remote Behavioural Treatment for Tics study, company data, expert opinion and additional literature.</p><p><strong>Results: </strong>We identified three trials reported across 14 publications: 2 comparing Online Remote Behavioural Treatment for Tics with online psychoeducation, and 1 comparing Neupulse with sham stimulation and a waitlist control. All were assessed as low risk of bias. Meta-analysis of the 2 Online Remote Behavioural Treatment for Tics studies (445 participants) showed significantly lower Yale Global Tic Severity Scale - Total Tic Severity Score at 3 and 12 months compared to online psychoeducation. Results of secondary outcomes were mixed. Neupulse showed significantly lower Yale Global Tic Severity Scale - Total Tic Severity Score, and improvements in motor and phonic tic scores at 4 weeks compared to sham, but no differences in Yale Global Tic Severity Scale-Impairment or Premonitory Urge for Tics Scale - Revised scores. A definitive base-case incremental cost-effectiveness ratio could not be determined due to limited long-term data and uncertainty around long-term combinations of effectiveness and intervention costs in United Kingdom National Health Service practice. Probabilistic incremental cost-effectiveness ratios ranged from £642 per quality-adjusted life-year gained to Online Remote Behavioural Treatment for Tics being dominated. The probability of Online Remote Behavioural Treatment for Tics being cost-effective at a threshold value of £20,000 per quality-adjusted life-year ranged from 52% to 89% across a range of scenarios. Cost-effectiveness results for Neupulse were even more uncertain due to a lack of published data, only a 4-week follow-up and uncertainty surrounding the intervention c","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 8","pages":"1-67"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113089","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}
Zoe Ward, Ruth Simmons, Hannah Fraser, Adam Trickey, Joanna Kesten, Andrew Gibson, Leila Reid, Sean Cox, Fiona Gordon, Stuart McPherson, Stephen Ryder, Francisco Javier Vilar, Alec Miners, Jack Williams, Beatrice Emmanouil, Monica Desai, Laura Coughlan, Ross Harris, Graham R Foster, Matthew Hickman, Sema Mandal, Peter Vickerman
<p><strong>Background: </strong>People who inject drugs are disproportionately affected by hepatitis C virus. The emergence of direct-acting antiviral treatments for hepatitis C virus motivated England to achieve the World Health Organization's elimination target of decreasing hepatitis C virus incidence among people who inject drugs to < 2 per 100 person-years (/100 person-years) by 2030. We determined whether existing testing and treatment strategies will reach this target in England, or whether improved strategies are needed and whether they are cost-effective.</p><p><strong>Methods: </strong>A dynamic hepatitis C virus transmission model among people who inject drugs was developed for four English regions. The model included the pathway from testing to treatment in prisons, drug treatment centres and other settings. Each pathway was parameterised using region-specific data, with yearly bio-behavioural surveys among people who inject drugs being used to parameterise and calibrate the model in a Bayesian framework. The model projected whether each region will reach the hepatitis C virus incidence target or what improvements (in testing and linkage to treatment) are needed from 2024 to achieve it. Hepatitis C virus care pathway costs were collated through interviews with practitioners and the published literature. The mean incremental cost-effectiveness ratio (per quality-adjusted life-year saved) was estimated for any 'improved' strategy that reached the incidence target compared to the baseline strategy. Incremental cost-effectiveness ratios were compared to a willingness-to-pay threshold of £20,000/quality-adjusted life-year saved over a 50-year time horizon (3.5% annual discount rate).</p><p><strong>Results: </strong>Across the four regions over 2016-22, an estimated 8831-9689 treatments occurred among 37,230 people who inject drugs, with the annual number treated increasing in prisons (7.8 times) and drug treatment centres (3.6 times). Model projections suggest that hepatitis C virus incidence among people who inject drugs has decreased across the regions by 56.1-85.4% (range of medians) over 2015-22, with incidence decreasing by 79.7-98.6% to 0.2-2.2/100 person-years by 2030. The World Health Organization incidence target (< 2/100 person-years) will be reached with > 80% probability in three regions and 40% probability in the other region. The probability of reaching the incidence target increases to > 65% in this region if screening is increased in drug treatment centres (80% screened annually) or prisons (75% of people get tested during their prison stay), with these screening strategies being cost-effective.</p><p><strong>Conclusion: </strong>Numerous England regions may be on target to decrease hepatitis C virus incidence among people who inject drugs to < 2/100 person-years. In regions that are not on target, further scale-up of testing in drug treatment centre or prison from 2024 could enable them to reach the World Health Organizati
{"title":"The impact and cost-effectiveness of scaling up HCV treatment for achieving elimination among people who inject drugs in England: a synopsis including evidence synthesis and economic modelling.","authors":"Zoe Ward, Ruth Simmons, Hannah Fraser, Adam Trickey, Joanna Kesten, Andrew Gibson, Leila Reid, Sean Cox, Fiona Gordon, Stuart McPherson, Stephen Ryder, Francisco Javier Vilar, Alec Miners, Jack Williams, Beatrice Emmanouil, Monica Desai, Laura Coughlan, Ross Harris, Graham R Foster, Matthew Hickman, Sema Mandal, Peter Vickerman","doi":"10.3310/GJPV1707","DOIUrl":"10.3310/GJPV1707","url":null,"abstract":"<p><strong>Background: </strong>People who inject drugs are disproportionately affected by hepatitis C virus. The emergence of direct-acting antiviral treatments for hepatitis C virus motivated England to achieve the World Health Organization's elimination target of decreasing hepatitis C virus incidence among people who inject drugs to < 2 per 100 person-years (/100 person-years) by 2030. We determined whether existing testing and treatment strategies will reach this target in England, or whether improved strategies are needed and whether they are cost-effective.</p><p><strong>Methods: </strong>A dynamic hepatitis C virus transmission model among people who inject drugs was developed for four English regions. The model included the pathway from testing to treatment in prisons, drug treatment centres and other settings. Each pathway was parameterised using region-specific data, with yearly bio-behavioural surveys among people who inject drugs being used to parameterise and calibrate the model in a Bayesian framework. The model projected whether each region will reach the hepatitis C virus incidence target or what improvements (in testing and linkage to treatment) are needed from 2024 to achieve it. Hepatitis C virus care pathway costs were collated through interviews with practitioners and the published literature. The mean incremental cost-effectiveness ratio (per quality-adjusted life-year saved) was estimated for any 'improved' strategy that reached the incidence target compared to the baseline strategy. Incremental cost-effectiveness ratios were compared to a willingness-to-pay threshold of £20,000/quality-adjusted life-year saved over a 50-year time horizon (3.5% annual discount rate).</p><p><strong>Results: </strong>Across the four regions over 2016-22, an estimated 8831-9689 treatments occurred among 37,230 people who inject drugs, with the annual number treated increasing in prisons (7.8 times) and drug treatment centres (3.6 times). Model projections suggest that hepatitis C virus incidence among people who inject drugs has decreased across the regions by 56.1-85.4% (range of medians) over 2015-22, with incidence decreasing by 79.7-98.6% to 0.2-2.2/100 person-years by 2030. The World Health Organization incidence target (< 2/100 person-years) will be reached with > 80% probability in three regions and 40% probability in the other region. The probability of reaching the incidence target increases to > 65% in this region if screening is increased in drug treatment centres (80% screened annually) or prisons (75% of people get tested during their prison stay), with these screening strategies being cost-effective.</p><p><strong>Conclusion: </strong>Numerous England regions may be on target to decrease hepatitis C virus incidence among people who inject drugs to < 2/100 person-years. In regions that are not on target, further scale-up of testing in drug treatment centre or prison from 2024 could enable them to reach the World Health Organizati","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 7","pages":"1-14"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113131","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 Kirkham, Eleni Gkini, Catherine Moakes, Sue Tohill, Jennifer A Hutcheon, Joel Singer, Jon Dorling, Clive Stubbs, Marcus Green, Mishal Javed, Jesse Kigozi, Ben Mol, Pollyanna Hardy, Jim Thornton, Peter von Dadelszen, Laura A Magee
<p><strong>Background: </strong>For women with chronic or gestational hypertension who remain well, early term birth (at 37-38 weeks' gestation) may reduce maternal complications, caesareans and stillbirths, but it may increase neonatal morbidity compared with expectant care. Expectant care may increase costs. There are no high-quality data to guide care, which currently involves maternal-fetal surveillance and intervention for maternal or fetal compromise, which may be rapid or unexpected.</p><p><strong>Objective: </strong>To investigate optimal timing of birth for women with chronic or gestational hypertension who reach term and remain well.</p><p><strong>Design: </strong>Pragmatic, unmasked, multicentre randomised trial with a health economic analysis.</p><p><strong>Setting: </strong>Fifty United Kingdom hospitals.</p><p><strong>Participants: </strong>Inclusion: maternal age ≥ 16 years, chronic or gestational hypertension, singleton pregnancy, live fetus, 36<sup>+0</sup>-37<sup>+6</sup> weeks' gestation and able to give documented informed consent. Exclusion: contraindication to either trial arm (e.g. pre-eclampsia), blood pressure ≥ 160/110 mmHg until controlled, major fetal anomaly anticipated to require neonatal care unit admission or participation in another timed birth trial.</p><p><strong>Interventions: </strong>Planned early term birth at 38<sup>+0-3</sup> weeks' (intervention) or 'usual care at term' (control, revised from 'expectant care until at least 40<sup>+0</sup> weeks', August 2022).</p><p><strong>Main outcome measures: </strong>Maternal coprimary: composite of 'poor maternal outcome' (severe hypertension, maternal death or maternal morbidity and superiority hypothesis). Neonatal coprimary: neonatal care unit admission ≥ 4 hours (non-inferiority hypothesis). Each coprimary is measured until primary hospital discharge or 28 days post birth (whichever is earlier). Key secondary: caesarean birth.</p><p><strong>Randomisation: </strong>1 : 1 ratio, minimised for key prognostic variables: site, hypertension type and prior caesarean.</p><p><strong>Blinding: </strong>It was not possible to mask care providers or participants to the intervention. For the coprimary maternal outcome, there was local site principal investigator/delegate sign-off based on review, masked to allocated group, of primary case notes.</p><p><strong>Results: </strong>From 2019 to 2022, 403 participants were randomised (37% of target 1080) to intervention (<i>n</i> = 201) or control (<i>n</i> = 202). The funder stopped the trial during the coronavirus disease discovered in 2019 pandemic for delayed recruitment. In the intervention (vs. control) group, birth was a median of 0.9 weeks earlier (38.4, interquartile range 38.3-38.6 vs. 39.3, interquartile range 38.7-39.9 weeks). There was no evidence of a difference in 'poor maternal outcome' (13% vs. 12%, respectively; adjusted risk ratio 1.16, 95% confidence interval 0.72 to 1.87). For 'neonatal care unit admission ≥ 4
{"title":"Timing of birth to improve outcomes in chronic or gestational hypertension: the WILL RCT.","authors":"Katie Kirkham, Eleni Gkini, Catherine Moakes, Sue Tohill, Jennifer A Hutcheon, Joel Singer, Jon Dorling, Clive Stubbs, Marcus Green, Mishal Javed, Jesse Kigozi, Ben Mol, Pollyanna Hardy, Jim Thornton, Peter von Dadelszen, Laura A Magee","doi":"10.3310/AAVV3131","DOIUrl":"10.3310/AAVV3131","url":null,"abstract":"<p><strong>Background: </strong>For women with chronic or gestational hypertension who remain well, early term birth (at 37-38 weeks' gestation) may reduce maternal complications, caesareans and stillbirths, but it may increase neonatal morbidity compared with expectant care. Expectant care may increase costs. There are no high-quality data to guide care, which currently involves maternal-fetal surveillance and intervention for maternal or fetal compromise, which may be rapid or unexpected.</p><p><strong>Objective: </strong>To investigate optimal timing of birth for women with chronic or gestational hypertension who reach term and remain well.</p><p><strong>Design: </strong>Pragmatic, unmasked, multicentre randomised trial with a health economic analysis.</p><p><strong>Setting: </strong>Fifty United Kingdom hospitals.</p><p><strong>Participants: </strong>Inclusion: maternal age ≥ 16 years, chronic or gestational hypertension, singleton pregnancy, live fetus, 36<sup>+0</sup>-37<sup>+6</sup> weeks' gestation and able to give documented informed consent. Exclusion: contraindication to either trial arm (e.g. pre-eclampsia), blood pressure ≥ 160/110 mmHg until controlled, major fetal anomaly anticipated to require neonatal care unit admission or participation in another timed birth trial.</p><p><strong>Interventions: </strong>Planned early term birth at 38<sup>+0-3</sup> weeks' (intervention) or 'usual care at term' (control, revised from 'expectant care until at least 40<sup>+0</sup> weeks', August 2022).</p><p><strong>Main outcome measures: </strong>Maternal coprimary: composite of 'poor maternal outcome' (severe hypertension, maternal death or maternal morbidity and superiority hypothesis). Neonatal coprimary: neonatal care unit admission ≥ 4 hours (non-inferiority hypothesis). Each coprimary is measured until primary hospital discharge or 28 days post birth (whichever is earlier). Key secondary: caesarean birth.</p><p><strong>Randomisation: </strong>1 : 1 ratio, minimised for key prognostic variables: site, hypertension type and prior caesarean.</p><p><strong>Blinding: </strong>It was not possible to mask care providers or participants to the intervention. For the coprimary maternal outcome, there was local site principal investigator/delegate sign-off based on review, masked to allocated group, of primary case notes.</p><p><strong>Results: </strong>From 2019 to 2022, 403 participants were randomised (37% of target 1080) to intervention (<i>n</i> = 201) or control (<i>n</i> = 202). The funder stopped the trial during the coronavirus disease discovered in 2019 pandemic for delayed recruitment. In the intervention (vs. control) group, birth was a median of 0.9 weeks earlier (38.4, interquartile range 38.3-38.6 vs. 39.3, interquartile range 38.7-39.9 weeks). There was no evidence of a difference in 'poor maternal outcome' (13% vs. 12%, respectively; adjusted risk ratio 1.16, 95% confidence interval 0.72 to 1.87). For 'neonatal care unit admission ≥ 4","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 2","pages":"1-28"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12862530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003378","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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