Kurinchi Gurusamy, Jeffrey Leung, Claire Vale, Danielle Roberts, Audrey Linden, Xiao Wei Tan, Priyal Taribagil, Sonam Patel, Elena Pizzo, Brian Davidson, Tim Mould, Mark Saunders, Omer Aziz, Sarah O'Dwyer
<p><strong>Background: </strong>We compared the relative benefits, harms and cost-effectiveness of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery ± systemic chemotherapy versus cytoreductive surgery ± systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric or ovarian cancers by a systematic review, meta-analysis and model-based cost-utility analysis.</p><p><strong>Methods: </strong>We searched MEDLINE, EMBASE, Cochrane Library and the Science Citation Index, ClinicalTrials.gov and WHO ICTRP trial registers until 14 April 2022. We included only randomised controlled trials addressing the research objectives. We used the Cochrane risk of bias tool version 2 to assess the risk of bias in randomised controlled trials. We used the random-effects model for data synthesis when applicable. For the cost-effectiveness analysis, we performed a model-based cost-utility analysis using methods recommended by The National Institute for Health and Care Excellence.</p><p><strong>Results: </strong>The systematic review included a total of eight randomised controlled trials (seven randomised controlled trials, 955 participants included in the quantitative analysis). All comparisons other than those for stage III or greater epithelial ovarian cancer contained only one trial, indicating the paucity of randomised controlled trials that provided data. For colorectal cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably results in little to no difference in all-cause mortality (60.6% vs. 60.6%; hazard ratio 1.00, 95% confidence interval 0.63 to 1.58) and may increase the serious adverse event proportions compared to cytoreductive surgery ± systemic chemotherapy (25.6% vs. 15.2%; risk ratio 1.69, 95% confidence interval 1.03 to 2.77). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone (40.8% vs. 60.8%; hazard ratio 0.55, 95% confidence interval 0.32 to 0.95). For gastric cancer, there is high uncertainty about the effects of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy versus cytoreductive surgery + systemic chemotherapy or systemic chemotherapy alone on all-cause mortality. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to cytoreductive surgery + systemic chemotherapy (46.3% vs. 57.4%; hazard ratio 0.73, 95% confidence interval 0.57 to 0.93). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy may not be cost-effective versus cytoreductive surgery + systemic chemotherapy for colorectal
背景：我们通过系统综述、荟萃分析和基于模型的成本效用分析，比较了在结直肠癌、胃癌或卵巢癌腹膜转移患者中，热疗术中腹膜化疗+细胞减灭术±全身化疗与细胞减灭术±全身化疗或单纯全身化疗的相对益处、危害和成本效用：截至 2022 年 4 月 14 日，我们检索了 MEDLINE、EMBASE、Cochrane 图书馆和科学引文索引、ClinicalTrials.gov 和 WHO ICTRP 试验登记。我们只纳入了针对研究目标的随机对照试验。我们使用 Cochrane 第 2 版偏倚风险工具来评估随机对照试验的偏倚风险。在适用的情况下，我们使用随机效应模型进行数据综合。在成本效益分析中，我们采用美国国家健康与护理卓越研究所推荐的方法进行了基于模型的成本效益分析：系统综述共包括 8 项随机对照试验（7 项随机对照试验，955 名参与者参与了定量分析）。除了针对 III 期或以上上皮性卵巢癌的比较外，其他所有比较都只包含一项试验，这表明提供数据的随机对照试验很少。对于结直肠癌，术中热腹膜化疗+细胞减灭术+全身化疗可能导致的全因死亡率几乎没有差异（60.6% vs. 60.6%；危险比 1.00，95% 置信区间 0.63 至 1.58），但与细胞减灭术+全身化疗相比，可能会增加严重不良事件的比例（25.6% vs. 15.2%；危险比 1.69，95% 置信区间 1.03 至 2.77）。与单纯氟尿嘧啶类全身化疗相比，术中腹膜热化疗+细胞切除手术+全身化疗可能会降低全因死亡率（40.8% 对 60.8%；危险比 0.55，95% 置信区间 0.32 至 0.95）。对于胃癌，术中腹膜热化疗+细胞切除手术+全身化疗与细胞切除手术+全身化疗或单纯全身化疗对全因死亡率的影响存在很大的不确定性。对于接受间歇性细胞减灭术的 III 期或以上上皮性卵巢癌患者，与细胞减灭术+全身化疗相比，术中腹腔热化疗+细胞减灭术+全身化疗可能会降低全因死亡率（46.3% 对 57.4%；危险比 0.73，95% 置信区间 0.57 至 0.93）。在结直肠癌方面，术中腹膜热化疗+细胞切除手术+全身化疗与细胞切除手术+全身化疗相比可能不具成本效益，但在其余比较中可能具有成本效益：我们无法按计划获得个体参与者的数据。每项比较的随机对照试验数量有限，健康相关生活质量方面的数据较少，这意味着随着新证据（来自偏倚风险较低的试验）的出现，建议可能会发生变化：结论：对于腹膜转移有限且可能承受大手术的结直肠癌腹膜转移患者，常规临床实践中不应采用腹腔内热化疗+细胞减灭术+全身化疗（强烈建议）。对于胃癌腹膜转移患者是否应进行术中腹腔热化疗+细胞减灭术+全身化疗或细胞减灭术+全身化疗，还存在很大的不确定性（不推荐）。对于Ⅲ期或Ⅲ期以上上皮性卵巢癌、转移灶局限于腹部、化疗后需要并可能耐受间歇性细胞减灭术的女性患者，应常规进行术中腹膜热化疗+细胞减灭术+全身化疗（强烈建议）：研究注册：研究注册：本研究注册为PROSPERO CRD42019130504：该奖项由美国国家健康与护理研究所（NIHR）健康技术评估项目资助（NIHR奖项编号：17/135/02），全文发表于《健康技术评估》第28卷第51期。如需了解更多奖项信息，请参阅 NIHR Funding and Awards 网站。
{"title":"Hyperthermic intraoperative peritoneal chemotherapy and cytoreductive surgery for people with peritoneal metastases: a systematic review and cost-effectiveness analysis.","authors":"Kurinchi Gurusamy, Jeffrey Leung, Claire Vale, Danielle Roberts, Audrey Linden, Xiao Wei Tan, Priyal Taribagil, Sonam Patel, Elena Pizzo, Brian Davidson, Tim Mould, Mark Saunders, Omer Aziz, Sarah O'Dwyer","doi":"10.3310/KWDG6338","DOIUrl":"10.3310/KWDG6338","url":null,"abstract":"<p><strong>Background: </strong>We compared the relative benefits, harms and cost-effectiveness of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery ± systemic chemotherapy versus cytoreductive surgery ± systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric or ovarian cancers by a systematic review, meta-analysis and model-based cost-utility analysis.</p><p><strong>Methods: </strong>We searched MEDLINE, EMBASE, Cochrane Library and the Science Citation Index, ClinicalTrials.gov and WHO ICTRP trial registers until 14 April 2022. We included only randomised controlled trials addressing the research objectives. We used the Cochrane risk of bias tool version 2 to assess the risk of bias in randomised controlled trials. We used the random-effects model for data synthesis when applicable. For the cost-effectiveness analysis, we performed a model-based cost-utility analysis using methods recommended by The National Institute for Health and Care Excellence.</p><p><strong>Results: </strong>The systematic review included a total of eight randomised controlled trials (seven randomised controlled trials, 955 participants included in the quantitative analysis). All comparisons other than those for stage III or greater epithelial ovarian cancer contained only one trial, indicating the paucity of randomised controlled trials that provided data. For colorectal cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably results in little to no difference in all-cause mortality (60.6% vs. 60.6%; hazard ratio 1.00, 95% confidence interval 0.63 to 1.58) and may increase the serious adverse event proportions compared to cytoreductive surgery ± systemic chemotherapy (25.6% vs. 15.2%; risk ratio 1.69, 95% confidence interval 1.03 to 2.77). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone (40.8% vs. 60.8%; hazard ratio 0.55, 95% confidence interval 0.32 to 0.95). For gastric cancer, there is high uncertainty about the effects of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy versus cytoreductive surgery + systemic chemotherapy or systemic chemotherapy alone on all-cause mortality. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to cytoreductive surgery + systemic chemotherapy (46.3% vs. 57.4%; hazard ratio 0.73, 95% confidence interval 0.57 to 0.93). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy may not be cost-effective versus cytoreductive surgery + systemic chemotherapy for colorectal","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 51","pages":"1-139"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142285845","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 Marshman, Hannah Ainsworth, Caroline Fairhurst, Katie Whiteside, Debbie Sykes, Anju Keetharuth, Sarab El Yousfi, Emma Turner, Peter F Day, Ivor G Chestnutt, Simon Dixon, Ian Kellar, Fiona Gilchrist, Mark Robertson, Sue Pavitt, Catherine Hewitt, Donna Dey, David Torgerson, Lesley Pollard, Emma Manser, Nassar Seifo, Mariana Araujo, Waraf Al-Yaseen, Claire Jones, Kate Hicks, Kathryn Rowles, Nicola Innes
<p><strong>Background: </strong>The presence of dental caries impacts on children's daily lives, particularly among those living in deprived areas. There are successful interventions across the United Kingdom for young children based on toothbrushing with fluoride toothpaste. However, evidence is lacking for oral health improvement programmes in secondary-school pupils to reduce dental caries and its sequelae.</p><p><strong>Objectives: </strong>To determine the clinical and cost effectiveness of a behaviour change intervention promoting toothbrushing for preventing dental caries in secondary-school pupils.</p><p><strong>Design: </strong>A multicentre, school-based, assessor-blinded, two-arm cluster randomised controlled trial with an internal pilot and embedded health economic and process evaluations.</p><p><strong>Setting: </strong>Secondary schools in Scotland, England and Wales with above-average proportion of pupils eligible for free school meals. Randomisation occurred within schools (year-group level), using block randomisation stratified by school.</p><p><strong>Participants: </strong>Pupils aged 11-13 years at recruitment, who have their own mobile telephone.</p><p><strong>Interventions: </strong>Two-component intervention based on behaviour change theory: (1) 50-minute lesson delivered by teachers, and (2) twice-daily text messages to pupils' mobile phones about toothbrushing, compared with routine education.</p><p><strong>Main outcome measures: </strong>Primary outcome: presence of at least one treated or untreated carious lesion using D<sub>ICDAS4-6</sub>MFT (Decayed, Missing and Filled Teeth) in any permanent tooth, measured at pupil level at 2.5 years. Secondary outcomes included: number of D<sub>ICDAS4-6</sub>MFT; presence and number of D<sub>ICDAS1-6</sub>MFT; plaque; bleeding; twice-daily toothbrushing; health-related quality of life (Child Health Utility 9D); and oral health-related quality of life (Caries Impacts and Experiences Questionnaire for Children).</p><p><strong>Results: </strong>Four thousand six hundred and eighty pupils (intervention, <i>n</i> = 2262; control, <i>n</i> = 2418) from 42 schools were randomised. The primary analysis on 2383 pupils (50.9%; intervention 1153, 51.0%; control 1230, 50.9%) with valid data at baseline and 2.5 years found 44.6% in the intervention group and 43.0% in control had obvious decay experience in at least one permanent tooth. There was no evidence of a difference (odds ratio 1.04, 95% confidence interval 0.85 to 1.26, <i>p</i> = 0.72) and no statistically significant differences in secondary outcomes except for twice-daily toothbrushing at 6 months (odds ratio 1.30, 95% confidence interval 1.03 to 1.63, <i>p</i> = 0.03) and gingival bleeding score (borderline) at 2.5 years (geometric mean difference 0.92, 95% confidence interval 0.85 to 1.00, <i>p</i> = 0.05). The intervention had higher incremental mean costs (£1.02, 95% confidence interval -1.29 to 3.23) and lower incremental mean q
{"title":"Behaviour change intervention (education and text) to prevent dental caries in secondary school pupils: BRIGHT RCT, process and economic evaluation.","authors":"Zoe Marshman, Hannah Ainsworth, Caroline Fairhurst, Katie Whiteside, Debbie Sykes, Anju Keetharuth, Sarab El Yousfi, Emma Turner, Peter F Day, Ivor G Chestnutt, Simon Dixon, Ian Kellar, Fiona Gilchrist, Mark Robertson, Sue Pavitt, Catherine Hewitt, Donna Dey, David Torgerson, Lesley Pollard, Emma Manser, Nassar Seifo, Mariana Araujo, Waraf Al-Yaseen, Claire Jones, Kate Hicks, Kathryn Rowles, Nicola Innes","doi":"10.3310/JQTA2103","DOIUrl":"10.3310/JQTA2103","url":null,"abstract":"<p><strong>Background: </strong>The presence of dental caries impacts on children's daily lives, particularly among those living in deprived areas. There are successful interventions across the United Kingdom for young children based on toothbrushing with fluoride toothpaste. However, evidence is lacking for oral health improvement programmes in secondary-school pupils to reduce dental caries and its sequelae.</p><p><strong>Objectives: </strong>To determine the clinical and cost effectiveness of a behaviour change intervention promoting toothbrushing for preventing dental caries in secondary-school pupils.</p><p><strong>Design: </strong>A multicentre, school-based, assessor-blinded, two-arm cluster randomised controlled trial with an internal pilot and embedded health economic and process evaluations.</p><p><strong>Setting: </strong>Secondary schools in Scotland, England and Wales with above-average proportion of pupils eligible for free school meals. Randomisation occurred within schools (year-group level), using block randomisation stratified by school.</p><p><strong>Participants: </strong>Pupils aged 11-13 years at recruitment, who have their own mobile telephone.</p><p><strong>Interventions: </strong>Two-component intervention based on behaviour change theory: (1) 50-minute lesson delivered by teachers, and (2) twice-daily text messages to pupils' mobile phones about toothbrushing, compared with routine education.</p><p><strong>Main outcome measures: </strong>Primary outcome: presence of at least one treated or untreated carious lesion using D<sub>ICDAS4-6</sub>MFT (Decayed, Missing and Filled Teeth) in any permanent tooth, measured at pupil level at 2.5 years. Secondary outcomes included: number of D<sub>ICDAS4-6</sub>MFT; presence and number of D<sub>ICDAS1-6</sub>MFT; plaque; bleeding; twice-daily toothbrushing; health-related quality of life (Child Health Utility 9D); and oral health-related quality of life (Caries Impacts and Experiences Questionnaire for Children).</p><p><strong>Results: </strong>Four thousand six hundred and eighty pupils (intervention, <i>n</i> = 2262; control, <i>n</i> = 2418) from 42 schools were randomised. The primary analysis on 2383 pupils (50.9%; intervention 1153, 51.0%; control 1230, 50.9%) with valid data at baseline and 2.5 years found 44.6% in the intervention group and 43.0% in control had obvious decay experience in at least one permanent tooth. There was no evidence of a difference (odds ratio 1.04, 95% confidence interval 0.85 to 1.26, <i>p</i> = 0.72) and no statistically significant differences in secondary outcomes except for twice-daily toothbrushing at 6 months (odds ratio 1.30, 95% confidence interval 1.03 to 1.63, <i>p</i> = 0.03) and gingival bleeding score (borderline) at 2.5 years (geometric mean difference 0.92, 95% confidence interval 0.85 to 1.00, <i>p</i> = 0.05). The intervention had higher incremental mean costs (£1.02, 95% confidence interval -1.29 to 3.23) and lower incremental mean q","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 52","pages":"1-142"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142285846","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}
Garry Alan Tew, Laura Wiley, Lesley Ward, Jessica Grace Hugill-Jones, Camila Sofia Maturana, Caroline Marie Fairhurst, Kerry Jane Bell, Laura Bissell, Alison Booth, Jenny Howsam, Valerie Mount, Tim Rapley, Sarah Jane Ronaldson, Fiona Rose, David John Torgerson, David Yates, Catherine Elizabeth Hewitt
Joe Carroll, Catalina Lopez Manzano, Eve Tomlinson, Ayman Sadek, Chris Cooper, Hayley E Jones, Lorraine Rowsell, John Knight, Andrew Mumford, Rachel Palmer, William Hollingworth, Nicky J Welton, Penny Whiting
<p><strong>Background: </strong>Stroke or transient ischaemic attack patients are at increased risk of secondary vascular events. Antiplatelet medications, most commonly clopidogrel, are prescribed to reduce this risk. Factors including <i>CYP2C19</i> genetic variants can hinder clopidogrel metabolism. Laboratory-based or point-of-care tests can detect these variants, enabling targeted treatment.</p><p><strong>Objective: </strong>To assess the effectiveness of genetic testing to identify clopidogrel resistance in people with ischaemic stroke or transient ischaemic attack. Specific objectives: Do people tested for clopidogrel resistance, and treated accordingly, have a reduced risk of secondary vascular events? Do people with loss-of-function alleles associated with clopidogrel resistance have a reduced risk of secondary vascular events if treated with alternative interventions compared to clopidogrel? Do people with loss-of-function alleles associated with clopidogrel resistance have an increased risk of secondary vascular events when treated with clopidogrel? What is the accuracy of point-of-care tests for detecting variants associated with clopidogrel resistance? What is the technical performance and cost of <i>CYP2C19</i> genetic tests? Is genetic testing for clopidogrel resistance cost-effective compared with no testing?</p><p><strong>Design: </strong>Systematic review and economic model.</p><p><strong>Results: </strong>Objective 1: Two studies assessed secondary vascular events in patients tested for loss-of-function alleles and treated accordingly. They found a reduced risk, but confidence intervals were wide (hazard ratio 0.50, 95% confidence interval 0.09 to 2.74 and hazard ratio 0.53, 95% confidence interval 0.24 to 1.18). Objective 2: Seven randomised controlled trials compared clopidogrel with alternative treatment in people with genetic variants. Ticagrelor was associated with a lower risk of secondary vascular events than clopidogrel (summary hazard ratio 0.76, 95% confidence interval 0.65 to 0.90; two studies). Objective 3: Twenty-five studies compared outcomes in people with and without genetic variants treated with clopidogrel. People with genetic variants were at an increased risk of secondary vascular events (hazard ratio 1.72, 95% confidence interval 1.43 to 2.08; 18 studies). There was no difference in bleeding risk (hazard ratio 0.98, 95% confidence interval 0.68 to 1.40; five studies). Objective 4: Eleven studies evaluated Genomadix Cube accuracy; no studies evaluated Genedrive. Summary sensitivity and specificity against laboratory reference standards were both 100% (95% confidence interval 94% to 100% and 99% to 100%). Objective 5: Seventeen studies evaluated technical performance of point-of-care tests. Test failure rate ranged from 0.4% to 19% for Genomadix Cube. A survey of 8/10 genomic laboratory hubs revealed variation in preferred technologies for testing, and cost per test ranging from £15 to £250. Most laboratories
{"title":"Clinical and cost-effectiveness of clopidogrel resistance genotype testing after ischaemic stroke or transient ischaemic attack: a systematic review and economic model.","authors":"Joe Carroll, Catalina Lopez Manzano, Eve Tomlinson, Ayman Sadek, Chris Cooper, Hayley E Jones, Lorraine Rowsell, John Knight, Andrew Mumford, Rachel Palmer, William Hollingworth, Nicky J Welton, Penny Whiting","doi":"10.3310/PWCB4016","DOIUrl":"10.3310/PWCB4016","url":null,"abstract":"<p><strong>Background: </strong>Stroke or transient ischaemic attack patients are at increased risk of secondary vascular events. Antiplatelet medications, most commonly clopidogrel, are prescribed to reduce this risk. Factors including <i>CYP2C19</i> genetic variants can hinder clopidogrel metabolism. Laboratory-based or point-of-care tests can detect these variants, enabling targeted treatment.</p><p><strong>Objective: </strong>To assess the effectiveness of genetic testing to identify clopidogrel resistance in people with ischaemic stroke or transient ischaemic attack. Specific objectives: Do people tested for clopidogrel resistance, and treated accordingly, have a reduced risk of secondary vascular events? Do people with loss-of-function alleles associated with clopidogrel resistance have a reduced risk of secondary vascular events if treated with alternative interventions compared to clopidogrel? Do people with loss-of-function alleles associated with clopidogrel resistance have an increased risk of secondary vascular events when treated with clopidogrel? What is the accuracy of point-of-care tests for detecting variants associated with clopidogrel resistance? What is the technical performance and cost of <i>CYP2C19</i> genetic tests? Is genetic testing for clopidogrel resistance cost-effective compared with no testing?</p><p><strong>Design: </strong>Systematic review and economic model.</p><p><strong>Results: </strong>Objective 1: Two studies assessed secondary vascular events in patients tested for loss-of-function alleles and treated accordingly. They found a reduced risk, but confidence intervals were wide (hazard ratio 0.50, 95% confidence interval 0.09 to 2.74 and hazard ratio 0.53, 95% confidence interval 0.24 to 1.18). Objective 2: Seven randomised controlled trials compared clopidogrel with alternative treatment in people with genetic variants. Ticagrelor was associated with a lower risk of secondary vascular events than clopidogrel (summary hazard ratio 0.76, 95% confidence interval 0.65 to 0.90; two studies). Objective 3: Twenty-five studies compared outcomes in people with and without genetic variants treated with clopidogrel. People with genetic variants were at an increased risk of secondary vascular events (hazard ratio 1.72, 95% confidence interval 1.43 to 2.08; 18 studies). There was no difference in bleeding risk (hazard ratio 0.98, 95% confidence interval 0.68 to 1.40; five studies). Objective 4: Eleven studies evaluated Genomadix Cube accuracy; no studies evaluated Genedrive. Summary sensitivity and specificity against laboratory reference standards were both 100% (95% confidence interval 94% to 100% and 99% to 100%). Objective 5: Seventeen studies evaluated technical performance of point-of-care tests. Test failure rate ranged from 0.4% to 19% for Genomadix Cube. A survey of 8/10 genomic laboratory hubs revealed variation in preferred technologies for testing, and cost per test ranging from £15 to £250. Most laboratories","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 57","pages":"1-194"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142285851","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}
Jan O Jansen, Jemma Hudson, Charlotte Kennedy, Claire Cochran, Graeme MacLennan, Katie Gillies, Robbie Lendrum, Samy Sadek, Dwayne Boyers, Gillian Ferry, Louisa Lawrie, Mintu Nath, Seonaidh Cotton, Samantha Wileman, Mark Forrest, Karim Brohi, Tim Harris, Fiona Lecky, Chris Moran, Jonathan J Morrison, John Norrie, Alan Paterson, Nigel Tai, Nick Welch, Marion K Campbell
<p><strong>Background: </strong>The most common cause of preventable death after injury is haemorrhage. Resuscitative endovascular balloon occlusion of the aorta is intended to provide earlier, temporary haemorrhage control, to facilitate transfer to an operating theatre or interventional radiology suite for definitive haemostasis.</p><p><strong>Objective: </strong>To compare standard care plus resuscitative endovascular balloon occlusion of the aorta versus standard care in patients with exsanguinating haemorrhage in the emergency department.</p><p><strong>Design: </strong>Pragmatic, multicentre, Bayesian, group-sequential, registry-enabled, open-label, parallel-group randomised controlled trial to determine the clinical and cost-effectiveness of standard care plus resuscitative endovascular balloon occlusion of the aorta, compared to standard care alone.</p><p><strong>Setting: </strong>United Kingdom Major Trauma Centres.</p><p><strong>Participants: </strong>Trauma patients aged 16 years or older with confirmed or suspected life-threatening torso haemorrhage deemed amenable to adjunctive treatment with resuscitative endovascular balloon occlusion of the aorta.</p><p><strong>Interventions: </strong>Participants were randomly assigned 1 : 1 to: standard care, as expected in a major trauma centre standard care plus resuscitative endovascular balloon occlusion of the aorta.</p><p><strong>Main outcome measures: </strong><i>Primary:</i> Mortality at 90 days. <i>Secondary:</i> Mortality at 6 months, while in hospital, and within 24, 6 and 3 hours; need for haemorrhage control procedures, time to commencement of haemorrhage procedure, complications, length of stay (hospital and intensive care unit-free days), blood product use. <i>Health economic:</i> Expected United Kingdom National Health Service perspective costs, life-years and quality-adjusted life-years, modelled over a lifetime horizon.</p><p><strong>Data sources: </strong>Case report forms, Trauma Audit and Research Network registry, NHS Digital (Hospital Episode Statistics and Office of National Statistics data).</p><p><strong>Results: </strong>Ninety patients were enrolled: 46 were randomised to standard care plus resuscitative endovascular balloon occlusion of the aorta and 44 to standard care. Mortality at 90 days was higher in the standard care plus resuscitative endovascular balloon occlusion of the aorta group (54%) compared to the standard care group (42%). The odds ratio was 1.58 (95% credible interval 0.72 to 3.52). The posterior probability of an odds ratio > 1 (indicating increased odds of death with resuscitative endovascular balloon occlusion of the aorta) was 86.9%. The overall effect did not change when an enthusiastic prior was used or when the estimate was adjusted for baseline characteristics. For the secondary outcomes (3, 6 and 24 hours mortality), the posterior probability that standard care plus resuscitative endovascular balloon occlusion of the aorta was harmful was hig
{"title":"The UK resuscitative endovascular balloon occlusion of the aorta in trauma patients with life-threatening torso haemorrhage: the (UK-REBOA) multicentre RCT.","authors":"Jan O Jansen, Jemma Hudson, Charlotte Kennedy, Claire Cochran, Graeme MacLennan, Katie Gillies, Robbie Lendrum, Samy Sadek, Dwayne Boyers, Gillian Ferry, Louisa Lawrie, Mintu Nath, Seonaidh Cotton, Samantha Wileman, Mark Forrest, Karim Brohi, Tim Harris, Fiona Lecky, Chris Moran, Jonathan J Morrison, John Norrie, Alan Paterson, Nigel Tai, Nick Welch, Marion K Campbell","doi":"10.3310/LTYV4082","DOIUrl":"10.3310/LTYV4082","url":null,"abstract":"<p><strong>Background: </strong>The most common cause of preventable death after injury is haemorrhage. Resuscitative endovascular balloon occlusion of the aorta is intended to provide earlier, temporary haemorrhage control, to facilitate transfer to an operating theatre or interventional radiology suite for definitive haemostasis.</p><p><strong>Objective: </strong>To compare standard care plus resuscitative endovascular balloon occlusion of the aorta versus standard care in patients with exsanguinating haemorrhage in the emergency department.</p><p><strong>Design: </strong>Pragmatic, multicentre, Bayesian, group-sequential, registry-enabled, open-label, parallel-group randomised controlled trial to determine the clinical and cost-effectiveness of standard care plus resuscitative endovascular balloon occlusion of the aorta, compared to standard care alone.</p><p><strong>Setting: </strong>United Kingdom Major Trauma Centres.</p><p><strong>Participants: </strong>Trauma patients aged 16 years or older with confirmed or suspected life-threatening torso haemorrhage deemed amenable to adjunctive treatment with resuscitative endovascular balloon occlusion of the aorta.</p><p><strong>Interventions: </strong>Participants were randomly assigned 1 : 1 to: standard care, as expected in a major trauma centre standard care plus resuscitative endovascular balloon occlusion of the aorta.</p><p><strong>Main outcome measures: </strong><i>Primary:</i> Mortality at 90 days. <i>Secondary:</i> Mortality at 6 months, while in hospital, and within 24, 6 and 3 hours; need for haemorrhage control procedures, time to commencement of haemorrhage procedure, complications, length of stay (hospital and intensive care unit-free days), blood product use. <i>Health economic:</i> Expected United Kingdom National Health Service perspective costs, life-years and quality-adjusted life-years, modelled over a lifetime horizon.</p><p><strong>Data sources: </strong>Case report forms, Trauma Audit and Research Network registry, NHS Digital (Hospital Episode Statistics and Office of National Statistics data).</p><p><strong>Results: </strong>Ninety patients were enrolled: 46 were randomised to standard care plus resuscitative endovascular balloon occlusion of the aorta and 44 to standard care. Mortality at 90 days was higher in the standard care plus resuscitative endovascular balloon occlusion of the aorta group (54%) compared to the standard care group (42%). The odds ratio was 1.58 (95% credible interval 0.72 to 3.52). The posterior probability of an odds ratio > 1 (indicating increased odds of death with resuscitative endovascular balloon occlusion of the aorta) was 86.9%. The overall effect did not change when an enthusiastic prior was used or when the estimate was adjusted for baseline characteristics. For the secondary outcomes (3, 6 and 24 hours mortality), the posterior probability that standard care plus resuscitative endovascular balloon occlusion of the aorta was harmful was hig","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 54","pages":"1-122"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142285848","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}
Tristan M Snowsill, Helen Coelho, Nia G Morrish, Simon Briscoe, Kate Boddy, Tracy Smith, Emma J Crosbie, Neil Aj Ryan, Fiona Lalloo, Claire T Hulme
<p><strong>Background: </strong>Lynch syndrome is an inherited condition which leads to an increased risk of colorectal, endometrial and ovarian cancer. Risk-reducing surgery is generally recommended to manage the risk of gynaecological cancer once childbearing is completed. The value of gynaecological colonoscopic surveillance as an interim measure or instead of risk-reducing surgery is uncertain. We aimed to determine whether gynaecological surveillance was effective and cost-effective in Lynch syndrome.</p><p><strong>Methods: </strong>We conducted systematic reviews of the effectiveness and cost-effectiveness of gynaecological cancer surveillance in Lynch syndrome, as well as a systematic review of health utility values relating to cancer and gynaecological risk reduction. Study identification included bibliographic database searching and citation chasing (searches updated 3 August 2021). Screening and assessment of eligibility for inclusion were conducted by independent researchers. Outcomes were prespecified and were informed by clinical experts and patient involvement. Data extraction and quality appraisal were conducted and results were synthesised narratively. We also developed a whole-disease economic model for Lynch syndrome using discrete event simulation methodology, including natural history components for colorectal, endometrial and ovarian cancer, and we used this model to conduct a cost-utility analysis of gynaecological risk management strategies, including surveillance, risk-reducing surgery and doing nothing.</p><p><strong>Results: </strong>We found 30 studies in the review of clinical effectiveness, of which 20 were non-comparative (single-arm) studies. There were no high-quality studies providing precise outcome estimates at low risk of bias. There is some evidence that mortality rate is higher for surveillance than for risk-reducing surgery but mortality is also higher for no surveillance than for surveillance. Some asymptomatic cancers were detected through surveillance but some cancers were also missed. There was a wide range of pain experiences, including some individuals feeling no pain and some feeling severe pain. The use of pain relief (e.g. ibuprofen) was common, and some women underwent general anaesthetic for surveillance. Existing economic evaluations clearly found that risk-reducing surgery leads to the best lifetime health (measured using quality-adjusted life-years) and is cost-effective, while surveillance is not cost-effective in comparison. Our economic evaluation found that a strategy of surveillance alone or offering surveillance and risk-reducing surgery was cost-effective, except for <i>path_PMS2</i> Lynch syndrome. Offering only risk-reducing surgery was less effective than offering surveillance with or without surgery.</p><p><strong>Limitations: </strong>Firm conclusions about clinical effectiveness could not be reached because of the lack of high-quality research. We did not assume that women would im
{"title":"Gynaecological cancer surveillance for women with Lynch syndrome: systematic review and cost-effectiveness evaluation.","authors":"Tristan M Snowsill, Helen Coelho, Nia G Morrish, Simon Briscoe, Kate Boddy, Tracy Smith, Emma J Crosbie, Neil Aj Ryan, Fiona Lalloo, Claire T Hulme","doi":"10.3310/VBXX6307","DOIUrl":"10.3310/VBXX6307","url":null,"abstract":"<p><strong>Background: </strong>Lynch syndrome is an inherited condition which leads to an increased risk of colorectal, endometrial and ovarian cancer. Risk-reducing surgery is generally recommended to manage the risk of gynaecological cancer once childbearing is completed. The value of gynaecological colonoscopic surveillance as an interim measure or instead of risk-reducing surgery is uncertain. We aimed to determine whether gynaecological surveillance was effective and cost-effective in Lynch syndrome.</p><p><strong>Methods: </strong>We conducted systematic reviews of the effectiveness and cost-effectiveness of gynaecological cancer surveillance in Lynch syndrome, as well as a systematic review of health utility values relating to cancer and gynaecological risk reduction. Study identification included bibliographic database searching and citation chasing (searches updated 3 August 2021). Screening and assessment of eligibility for inclusion were conducted by independent researchers. Outcomes were prespecified and were informed by clinical experts and patient involvement. Data extraction and quality appraisal were conducted and results were synthesised narratively. We also developed a whole-disease economic model for Lynch syndrome using discrete event simulation methodology, including natural history components for colorectal, endometrial and ovarian cancer, and we used this model to conduct a cost-utility analysis of gynaecological risk management strategies, including surveillance, risk-reducing surgery and doing nothing.</p><p><strong>Results: </strong>We found 30 studies in the review of clinical effectiveness, of which 20 were non-comparative (single-arm) studies. There were no high-quality studies providing precise outcome estimates at low risk of bias. There is some evidence that mortality rate is higher for surveillance than for risk-reducing surgery but mortality is also higher for no surveillance than for surveillance. Some asymptomatic cancers were detected through surveillance but some cancers were also missed. There was a wide range of pain experiences, including some individuals feeling no pain and some feeling severe pain. The use of pain relief (e.g. ibuprofen) was common, and some women underwent general anaesthetic for surveillance. Existing economic evaluations clearly found that risk-reducing surgery leads to the best lifetime health (measured using quality-adjusted life-years) and is cost-effective, while surveillance is not cost-effective in comparison. Our economic evaluation found that a strategy of surveillance alone or offering surveillance and risk-reducing surgery was cost-effective, except for <i>path_PMS2</i> Lynch syndrome. Offering only risk-reducing surgery was less effective than offering surveillance with or without surgery.</p><p><strong>Limitations: </strong>Firm conclusions about clinical effectiveness could not be reached because of the lack of high-quality research. We did not assume that women would im","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 41","pages":"1-228"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11403379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153872","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}
Victoria Hodgetts Morton, Catherine A Moakes, Jane Daniels, Lee Middleton, Andrew Shennan, Peter Brocklehurst, Fidan Israfil-Bayli, Andrew K Ewer, James Gray, Nigel Ab Simpson, Jane E Norman, Christoph Lees, Konstantinos Tryposkiadis, Clive Stubbs, Max Hughes, R Katie Morris, Philip Toozs-Hobson
<p><strong>Background: </strong>Second trimester miscarriage and preterm birth is a significant global problem. Surgical cervical cerclage is performed to prevent pregnancy loss and preterm birth. It utilises either a monofilament or braided suture. It is hypothesised that a braided material becomes colonised with pathogenic bacteria that causes vaginal dysbiosis, infection and cerclage failure.</p><p><strong>Objectives: </strong>The primary objective of the study was to examine the effectiveness of using a monofilament suture material as opposed to a braided suture material on pregnancy loss in women requiring a vaginal cervical cerclage.</p><p><strong>Design: </strong>Superiority open randomised controlled trial.</p><p><strong>Setting: </strong>Seventy-five maternity sites across the UK.</p><p><strong>Participants: </strong>Women experiencing a singleton pregnancy requiring a cervical cerclage.</p><p><strong>Interventions: </strong>Monofilament suture or braided suture.</p><p><strong>Main outcome measures: </strong>The primary outcome was pregnancy loss (miscarriage and perinatal mortality, including any stillbirth or neonatal death in the first week of life). Secondary outcomes included the core outcome set for preterm birth.</p><p><strong>Methods: </strong>Women were randomised on a 1 : 1 basis to monofilament or braided cerclage utilising a bespoke randomisation service with minimisation dependent on the site, indication for cerclage, intention to use progesterone and planned surgical technique. The inclusion criteria were three or more previous mid-trimester losses or preterm births, insertion of a cerclage in a previous pregnancy, a history of a mid-trimester loss or preterm birth with a shortened cervical length in the current pregnancy or in women who clinicians deemed at risk of preterm birth. The exclusion criteria were an emergency or rescue cerclage, age of < 18 years, being unable to give informed consent or the cerclage having to be placed abdominally. The original sample size was calculated based on a relative risk reduction of 41% from a pregnancy loss rate of 19% in the braided group to 11% in the monofilament group with 90% power and alpha at <i>p</i> = 0.05. The independent data monitoring committee noted a lower-than-anticipated pooled event rate within the trial and recommended an increase in sample size to 2050. The outcome data were collected using clinical record forms from the maternal and neonatal medical records and reported to Birmingham Clinical Trials Unit.</p><p><strong>Results: </strong>A total of 2049 women were randomised, after withdrawals and loss to follow-up, data on 1005 women in the monofilament group and 993 women in the braided group were included. The baseline demographics between the groups were similar. There was no evidence of a difference in pregnancy loss rates between the monofilament and braided groups (80/1003 vs. 75/993; adjusted risk ratio: 1.05, 95% confidence interval: 0.79 to 1.40; adjusted
{"title":"Cerclage suture type to prevent pregnancy loss in women requiring a vaginal cervical cerclage: the C-STICH RCT.","authors":"Victoria Hodgetts Morton, Catherine A Moakes, Jane Daniels, Lee Middleton, Andrew Shennan, Peter Brocklehurst, Fidan Israfil-Bayli, Andrew K Ewer, James Gray, Nigel Ab Simpson, Jane E Norman, Christoph Lees, Konstantinos Tryposkiadis, Clive Stubbs, Max Hughes, R Katie Morris, Philip Toozs-Hobson","doi":"10.3310/YKTW8402","DOIUrl":"10.3310/YKTW8402","url":null,"abstract":"<p><strong>Background: </strong>Second trimester miscarriage and preterm birth is a significant global problem. Surgical cervical cerclage is performed to prevent pregnancy loss and preterm birth. It utilises either a monofilament or braided suture. It is hypothesised that a braided material becomes colonised with pathogenic bacteria that causes vaginal dysbiosis, infection and cerclage failure.</p><p><strong>Objectives: </strong>The primary objective of the study was to examine the effectiveness of using a monofilament suture material as opposed to a braided suture material on pregnancy loss in women requiring a vaginal cervical cerclage.</p><p><strong>Design: </strong>Superiority open randomised controlled trial.</p><p><strong>Setting: </strong>Seventy-five maternity sites across the UK.</p><p><strong>Participants: </strong>Women experiencing a singleton pregnancy requiring a cervical cerclage.</p><p><strong>Interventions: </strong>Monofilament suture or braided suture.</p><p><strong>Main outcome measures: </strong>The primary outcome was pregnancy loss (miscarriage and perinatal mortality, including any stillbirth or neonatal death in the first week of life). Secondary outcomes included the core outcome set for preterm birth.</p><p><strong>Methods: </strong>Women were randomised on a 1 : 1 basis to monofilament or braided cerclage utilising a bespoke randomisation service with minimisation dependent on the site, indication for cerclage, intention to use progesterone and planned surgical technique. The inclusion criteria were three or more previous mid-trimester losses or preterm births, insertion of a cerclage in a previous pregnancy, a history of a mid-trimester loss or preterm birth with a shortened cervical length in the current pregnancy or in women who clinicians deemed at risk of preterm birth. The exclusion criteria were an emergency or rescue cerclage, age of < 18 years, being unable to give informed consent or the cerclage having to be placed abdominally. The original sample size was calculated based on a relative risk reduction of 41% from a pregnancy loss rate of 19% in the braided group to 11% in the monofilament group with 90% power and alpha at <i>p</i> = 0.05. The independent data monitoring committee noted a lower-than-anticipated pooled event rate within the trial and recommended an increase in sample size to 2050. The outcome data were collected using clinical record forms from the maternal and neonatal medical records and reported to Birmingham Clinical Trials Unit.</p><p><strong>Results: </strong>A total of 2049 women were randomised, after withdrawals and loss to follow-up, data on 1005 women in the monofilament group and 993 women in the braided group were included. The baseline demographics between the groups were similar. There was no evidence of a difference in pregnancy loss rates between the monofilament and braided groups (80/1003 vs. 75/993; adjusted risk ratio: 1.05, 95% confidence interval: 0.79 to 1.40; adjusted","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 40","pages":"1-44"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11403380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139881","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}
Moira Cruickshank, Jemma Hudson, Rodolfo Hernández, Magaly Aceves-Martins, Richard Quinton, Katie Gillies, Lorna S Aucott, Charlotte Kennedy, Paul Manson, Nicholas Oliver, Frederick Wu, Siladitya Bhattacharya, Waljit S Dhillo, Channa N Jayasena, Miriam Brazzelli
<p><strong>Background: </strong>Low levels of testosterone cause male hypogonadism, which is associated with sexual dysfunction, tiredness and reduced muscle strength and quality of life. Testosterone replacement therapy is commonly used for ameliorating symptoms of male hypogonadism, but there is uncertainty about the magnitude of its effects and its cardiovascular and cerebrovascular safety.</p><p><strong>Aims of the research: </strong>The primary aim was to evaluate the safety of testosterone replacement therapy. We also assessed the clinical and cost-effectiveness of testosterone replacement therapy for men with male hypogonadism, and the existing qualitative evidence on men's experience and acceptability of testosterone replacement therapy.</p><p><strong>Design: </strong>Evidence synthesis and individual participant data meta-analysis of effectiveness and safety, qualitative evidence synthesis and model-based cost-utility analysis.</p><p><strong>Data sources: </strong>Major electronic databases were searched from 1992 to February 2021 and were restricted to English-language publications.</p><p><strong>Methods: </strong>We conducted a systematic review with meta-analysis of individual participant data according to current methodological standards. Evidence was considered from placebo-controlled randomised controlled trials assessing the effects of any formulation of testosterone replacement therapy in men with male hypogonadism. Primary outcomes were mortality and cardiovascular and cerebrovascular events. Data were extracted by one reviewer and cross-checked by a second reviewer. The risk of bias was assessed using the Cochrane Risk of Bias tool. We performed one-stage meta-analyses using the acquired individual participant data and two-stage meta-analyses to integrate the individual participant data with data extracted from eligible studies that did not provide individual participant data. A decision-analytic Markov model was developed to evaluate the cost per quality-adjusted life-years of the use of testosterone replacement therapy in cohorts of patients of different starting ages.</p><p><strong>Results: </strong>We identified 35 trials (5601 randomised participants). Of these, 17 trials (3431 participants) provided individual participant data. There were too few deaths to assess mortality. There was no difference between the testosterone replacement therapy group (120/1601, 7.5%) and placebo group (110/1519, 7.2%) in the incidence of cardiovascular and/or cerebrovascular events (13 studies, odds ratio 1.07, 95% confidence interval 0.81 to 1.42; <i>p</i> = 0.62). Testosterone replacement therapy improved quality of life and sexual function in almost all patient subgroups. In the testosterone replacement therapy group, serum testosterone was higher while serum cholesterol, triglycerides, haemoglobin and haematocrit were all lower. We identified several themes from five qualitative studies showing how symptoms of low testosterone affect men
{"title":"The effects and safety of testosterone replacement therapy for men with hypogonadism: the TestES evidence synthesis and economic evaluation.","authors":"Moira Cruickshank, Jemma Hudson, Rodolfo Hernández, Magaly Aceves-Martins, Richard Quinton, Katie Gillies, Lorna S Aucott, Charlotte Kennedy, Paul Manson, Nicholas Oliver, Frederick Wu, Siladitya Bhattacharya, Waljit S Dhillo, Channa N Jayasena, Miriam Brazzelli","doi":"10.3310/JRYT3981","DOIUrl":"10.3310/JRYT3981","url":null,"abstract":"<p><strong>Background: </strong>Low levels of testosterone cause male hypogonadism, which is associated with sexual dysfunction, tiredness and reduced muscle strength and quality of life. Testosterone replacement therapy is commonly used for ameliorating symptoms of male hypogonadism, but there is uncertainty about the magnitude of its effects and its cardiovascular and cerebrovascular safety.</p><p><strong>Aims of the research: </strong>The primary aim was to evaluate the safety of testosterone replacement therapy. We also assessed the clinical and cost-effectiveness of testosterone replacement therapy for men with male hypogonadism, and the existing qualitative evidence on men's experience and acceptability of testosterone replacement therapy.</p><p><strong>Design: </strong>Evidence synthesis and individual participant data meta-analysis of effectiveness and safety, qualitative evidence synthesis and model-based cost-utility analysis.</p><p><strong>Data sources: </strong>Major electronic databases were searched from 1992 to February 2021 and were restricted to English-language publications.</p><p><strong>Methods: </strong>We conducted a systematic review with meta-analysis of individual participant data according to current methodological standards. Evidence was considered from placebo-controlled randomised controlled trials assessing the effects of any formulation of testosterone replacement therapy in men with male hypogonadism. Primary outcomes were mortality and cardiovascular and cerebrovascular events. Data were extracted by one reviewer and cross-checked by a second reviewer. The risk of bias was assessed using the Cochrane Risk of Bias tool. We performed one-stage meta-analyses using the acquired individual participant data and two-stage meta-analyses to integrate the individual participant data with data extracted from eligible studies that did not provide individual participant data. A decision-analytic Markov model was developed to evaluate the cost per quality-adjusted life-years of the use of testosterone replacement therapy in cohorts of patients of different starting ages.</p><p><strong>Results: </strong>We identified 35 trials (5601 randomised participants). Of these, 17 trials (3431 participants) provided individual participant data. There were too few deaths to assess mortality. There was no difference between the testosterone replacement therapy group (120/1601, 7.5%) and placebo group (110/1519, 7.2%) in the incidence of cardiovascular and/or cerebrovascular events (13 studies, odds ratio 1.07, 95% confidence interval 0.81 to 1.42; <i>p</i> = 0.62). Testosterone replacement therapy improved quality of life and sexual function in almost all patient subgroups. In the testosterone replacement therapy group, serum testosterone was higher while serum cholesterol, triglycerides, haemoglobin and haematocrit were all lower. We identified several themes from five qualitative studies showing how symptoms of low testosterone affect men","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 43","pages":"1-210"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153874","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}
Carrie Stewart, Hangjian Wu, Uma Alagappan, Augusto Azuara-Blanco, Anthony J King, Andrew J Tatham, Rodolfo Hernández, Bruce Lowe, Darian Shotton, Nana Appiah, Taylor Coffey, Thenmalar Vadiveloo, Graeme MacLennan, Katie Gillies
<p><strong>Background: </strong>Glaucoma is a chronic disease of the optic nerve and a leading cause of severe visual loss in the UK. Once patients have been diagnosed, they need regular monitoring at hospital eye services. Recent advances in technology mean patients with glaucoma can now monitor their disease at home. This could be more convenient for patients and potentially reduce costs and increase capacity for the NHS. However, it is uncertain whether self-monitoring would be acceptable or possible for patients with glaucoma.</p><p><strong>Objectives: </strong>The objectives were to: identify which patients are most appropriate for home monitoring; understand views of key stakeholders (patients, clinicians, researchers) on whether home glaucoma monitoring is feasible and acceptable; develop a conceptual framework for the economic evaluation of home glaucoma monitoring; and explore the need for and provide evidence on the design of a future study to evaluate the clinical and cost-effectiveness of digital technologies for home monitoring of glaucoma.</p><p><strong>Design: </strong>In-home Tracking of glaucoma: Reliability, Acceptability, and Cost (I-TRAC) was a multiphase mixed-methods feasibility study with key components informed by theoretical and conceptual frameworks.</p><p><strong>Setting: </strong>Expert glaucoma specialists in the UK recruited through professional glaucoma societies; study site staff and patient participants recruited through three UK hospital eye services (England, Scotland, Northern Ireland); and UK research teams recruited though existing networks.</p><p><strong>Intervention: </strong>Home tonometer that measures intraocular pressure and a tablet computer with a visual function application. Patients were asked to use the technology weekly for 12 weeks.</p><p><strong>Results: </strong>Forty-two patients were recruited. Retention and completion of follow-up procedures was successful, with 95% (<i>n</i> = 40) completing the 3-month follow-up clinic visits. Adherence to the interventions was generally high [adherence to both devices (i.e. ≥ 80% adherence) was 55%]. Overall, patients and healthcare professionals were cautiously optimistic about the acceptability of digital technologies for home monitoring of patients with glaucoma. While most clinicians were supportive of the potential advantages glaucoma home monitoring could offer, concerns about the technologies (e.g. reliability and potential to miss disease progression) and how they would fit into routine care need to be addressed. Additionally, clarity is required on defining the ideal population for this intervention. Plans for how to evaluate value for money in a future study were also identified. However, the study also highlighted several unknowns relating to core components of a future evaluative study that require addressing before progression to a definitive effectiveness trial.</p><p><strong>Limitations: </strong>The main limitation relates to our sample an
{"title":"Feasibility of in-home monitoring for people with glaucoma: the I-TRAC mixed-methods study.","authors":"Carrie Stewart, Hangjian Wu, Uma Alagappan, Augusto Azuara-Blanco, Anthony J King, Andrew J Tatham, Rodolfo Hernández, Bruce Lowe, Darian Shotton, Nana Appiah, Taylor Coffey, Thenmalar Vadiveloo, Graeme MacLennan, Katie Gillies","doi":"10.3310/GTWD6802","DOIUrl":"10.3310/GTWD6802","url":null,"abstract":"<p><strong>Background: </strong>Glaucoma is a chronic disease of the optic nerve and a leading cause of severe visual loss in the UK. Once patients have been diagnosed, they need regular monitoring at hospital eye services. Recent advances in technology mean patients with glaucoma can now monitor their disease at home. This could be more convenient for patients and potentially reduce costs and increase capacity for the NHS. However, it is uncertain whether self-monitoring would be acceptable or possible for patients with glaucoma.</p><p><strong>Objectives: </strong>The objectives were to: identify which patients are most appropriate for home monitoring; understand views of key stakeholders (patients, clinicians, researchers) on whether home glaucoma monitoring is feasible and acceptable; develop a conceptual framework for the economic evaluation of home glaucoma monitoring; and explore the need for and provide evidence on the design of a future study to evaluate the clinical and cost-effectiveness of digital technologies for home monitoring of glaucoma.</p><p><strong>Design: </strong>In-home Tracking of glaucoma: Reliability, Acceptability, and Cost (I-TRAC) was a multiphase mixed-methods feasibility study with key components informed by theoretical and conceptual frameworks.</p><p><strong>Setting: </strong>Expert glaucoma specialists in the UK recruited through professional glaucoma societies; study site staff and patient participants recruited through three UK hospital eye services (England, Scotland, Northern Ireland); and UK research teams recruited though existing networks.</p><p><strong>Intervention: </strong>Home tonometer that measures intraocular pressure and a tablet computer with a visual function application. Patients were asked to use the technology weekly for 12 weeks.</p><p><strong>Results: </strong>Forty-two patients were recruited. Retention and completion of follow-up procedures was successful, with 95% (<i>n</i> = 40) completing the 3-month follow-up clinic visits. Adherence to the interventions was generally high [adherence to both devices (i.e. ≥ 80% adherence) was 55%]. Overall, patients and healthcare professionals were cautiously optimistic about the acceptability of digital technologies for home monitoring of patients with glaucoma. While most clinicians were supportive of the potential advantages glaucoma home monitoring could offer, concerns about the technologies (e.g. reliability and potential to miss disease progression) and how they would fit into routine care need to be addressed. Additionally, clarity is required on defining the ideal population for this intervention. Plans for how to evaluate value for money in a future study were also identified. However, the study also highlighted several unknowns relating to core components of a future evaluative study that require addressing before progression to a definitive effectiveness trial.</p><p><strong>Limitations: </strong>The main limitation relates to our sample an","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 44","pages":"1-163"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153875","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}
Sophie Beese, Tuba S Avşar, Malcolm Price, David Quinn, Hoong S Lim, Janine Dretzke, Chidubem O Ogwulu, Pelham Barton, Louise Jackson, David Moore
<p><strong>Background: </strong>Selected patients with advanced heart failure ineligible for heart transplantation could benefit from left ventricular assist device therapy as 'destination therapy'. There is evidence of the efficacy of destination therapy; however, it is not currently commissioned within the United Kingdom National Health Service due to the lack of economic evidence.</p><p><strong>Objective: </strong>What is the clinical and cost-effectiveness of a left ventricular assist device compared to medical management for patients with advanced heart failure ineligible for heart transplantation (destination therapy)?</p><p><strong>Methods: </strong>A systematic review of evidence on the clinical and cost-effectiveness of left ventricular assist devices as destination therapy was undertaken including, where feasible, a network meta-analysis to provide an indirect estimate of the relative effectiveness of currently available left ventricular assist devices compared to medical management. For the systematic reviews, data sources searched (up to 11 January 2022) were Cochrane CENTRAL, MEDLINE and EMBASE via Ovid for primary studies, and Epistemonikos and Cochrane Database of Systematic Reviews for relevant systematic reviews. Trial registers were also searched, along with data and reports from intervention-specific registries. Economic studies were identified in EconLit, CEA registry and the NHS Economic Evaluation Database (NHS EED). The searches were supplemented by checking reference lists of included studies. An economic model (Markov) was developed to estimate the cost-effectiveness of left ventricular assist devices compared to medical management from the United Kingdom National Health Service/personal social service perspective. Deterministic and probabilistic sensitivity analyses were conducted to explore uncertainties. Where possible, all analyses focused on the only currently available left ventricular assist device (HeartMate 3<sup>TM</sup>, Abbott, Chicago, IL, USA) in the United Kingdom.</p><p><strong>Results: </strong>The clinical effectiveness review included 134 studies (240 articles). There were no studies directly comparing HeartMate 3 and medical management (a randomised trial is ongoing). The currently available left ventricular assist device improves patient survival and reduces stroke rates and complications compared to earlier devices and relative to medical management. For example, survival at 24 months is 77% with the HeartMate 3 device compared to 59% with the HeartMate II (MOMENTUM 3 trial). An indirect comparison demonstrated a reduction in mortality compared to medical management [relative risk of death 0.25 (95% confidence interval 0.13 to 0.47); 24 months; this study]. The cost-effectiveness review included 5 cost analyses and 14 economic evaluations covering different generations of devices and with different perspectives. The reported incremental costs per quality-adjusted life-year gained compared to medical
{"title":"Clinical and cost-effectiveness of left ventricular assist devices as destination therapy for advanced heart failure: systematic review and economic evaluation.","authors":"Sophie Beese, Tuba S Avşar, Malcolm Price, David Quinn, Hoong S Lim, Janine Dretzke, Chidubem O Ogwulu, Pelham Barton, Louise Jackson, David Moore","doi":"10.3310/MLFA4009","DOIUrl":"10.3310/MLFA4009","url":null,"abstract":"<p><strong>Background: </strong>Selected patients with advanced heart failure ineligible for heart transplantation could benefit from left ventricular assist device therapy as 'destination therapy'. There is evidence of the efficacy of destination therapy; however, it is not currently commissioned within the United Kingdom National Health Service due to the lack of economic evidence.</p><p><strong>Objective: </strong>What is the clinical and cost-effectiveness of a left ventricular assist device compared to medical management for patients with advanced heart failure ineligible for heart transplantation (destination therapy)?</p><p><strong>Methods: </strong>A systematic review of evidence on the clinical and cost-effectiveness of left ventricular assist devices as destination therapy was undertaken including, where feasible, a network meta-analysis to provide an indirect estimate of the relative effectiveness of currently available left ventricular assist devices compared to medical management. For the systematic reviews, data sources searched (up to 11 January 2022) were Cochrane CENTRAL, MEDLINE and EMBASE via Ovid for primary studies, and Epistemonikos and Cochrane Database of Systematic Reviews for relevant systematic reviews. Trial registers were also searched, along with data and reports from intervention-specific registries. Economic studies were identified in EconLit, CEA registry and the NHS Economic Evaluation Database (NHS EED). The searches were supplemented by checking reference lists of included studies. An economic model (Markov) was developed to estimate the cost-effectiveness of left ventricular assist devices compared to medical management from the United Kingdom National Health Service/personal social service perspective. Deterministic and probabilistic sensitivity analyses were conducted to explore uncertainties. Where possible, all analyses focused on the only currently available left ventricular assist device (HeartMate 3<sup>TM</sup>, Abbott, Chicago, IL, USA) in the United Kingdom.</p><p><strong>Results: </strong>The clinical effectiveness review included 134 studies (240 articles). There were no studies directly comparing HeartMate 3 and medical management (a randomised trial is ongoing). The currently available left ventricular assist device improves patient survival and reduces stroke rates and complications compared to earlier devices and relative to medical management. For example, survival at 24 months is 77% with the HeartMate 3 device compared to 59% with the HeartMate II (MOMENTUM 3 trial). An indirect comparison demonstrated a reduction in mortality compared to medical management [relative risk of death 0.25 (95% confidence interval 0.13 to 0.47); 24 months; this study]. The cost-effectiveness review included 5 cost analyses and 14 economic evaluations covering different generations of devices and with different perspectives. The reported incremental costs per quality-adjusted life-year gained compared to medical ","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 38","pages":"1-237"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072626","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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