Alexis Llewellyn, Thai Han Phung, Marta O Soares, Lucy Shepherd, David Glynn, Melissa Harden, Ruth Walker, Ana Duarte, Sofia Dias
<p><strong>Background: </strong>Magnetic resonance imaging localises cancer in the prostate, allowing for a targeted biopsy with or without transrectal ultrasound-guided systematic biopsy. Targeted biopsy methods include cognitive fusion, where prostate lesions suspicious on magnetic resonance imaging are targeted visually during live ultrasound, and software fusion, where computer software overlays the magnetic resonance imaging image onto the ultrasound in real time. The effectiveness and cost-effectiveness of software fusion technologies compared with cognitive fusion biopsy are uncertain.</p><p><strong>Objectives: </strong>To assess the clinical and cost-effectiveness of software fusion biopsy technologies in people with suspected localised and locally advanced prostate cancer. A systematic review was conducted to evaluate the diagnostic accuracy, clinical efficacy and practical implementation of nine software fusion devices compared to cognitive fusion biopsies, and with each other, in people with suspected prostate cancer. Comprehensive searches including MEDLINE, and Embase were conducted up to August 2022 to identify studies which compared software fusion and cognitive fusion biopsies in people with suspected prostate cancer. Risk of bias was assessed with quality assessment of diagnostic accuracy studies-comparative tool. A network meta-analysis comparing software and cognitive fusion with or without concomitant systematic biopsy, and systematic biopsy alone was conducted. Additional outcomes, including safety and usability, were synthesised narratively. A de novo decision model was developed to estimate the cost-effectiveness of targeted software fusion biopsy relative to cognitive fusion biopsy with or without concomitant systematic biopsy for prostate cancer identification in biopsy-naive people. Scenario analyses were undertaken to explore the robustness of the results to variation in the model data sources and alternative assumptions.</p><p><strong>Results: </strong>Twenty-three studies (3773 patients with software fusion, 2154 cognitive fusion) were included, of which 13 informed the main meta-analyses. Evidence was available for seven of the nine fusion devices specified in the protocol and at high risk of bias. The meta-analyses show that patients undergoing software fusion biopsy may have: (1) a lower probability of being classified as not having cancer, (2) similar probability of being classified as having non-clinically significant cancer (International Society of Urological Pathology grade 1) and (3) higher probability of being classified at higher International Society of Urological Pathology grades, particularly International Society of Urological Pathology 2. Similar results were obtained when comparing between same biopsy methods where both were combined with systematic biopsy. Evidence was insufficient to conclude whether any individual devices were superior to cognitive fusion, or whether some software fusion technologi
{"title":"MRI software and cognitive fusion biopsies in people with suspected prostate cancer: a systematic review, network meta-analysis and cost-effectiveness analysis.","authors":"Alexis Llewellyn, Thai Han Phung, Marta O Soares, Lucy Shepherd, David Glynn, Melissa Harden, Ruth Walker, Ana Duarte, Sofia Dias","doi":"10.3310/PLFG4210","DOIUrl":"10.3310/PLFG4210","url":null,"abstract":"<p><strong>Background: </strong>Magnetic resonance imaging localises cancer in the prostate, allowing for a targeted biopsy with or without transrectal ultrasound-guided systematic biopsy. Targeted biopsy methods include cognitive fusion, where prostate lesions suspicious on magnetic resonance imaging are targeted visually during live ultrasound, and software fusion, where computer software overlays the magnetic resonance imaging image onto the ultrasound in real time. The effectiveness and cost-effectiveness of software fusion technologies compared with cognitive fusion biopsy are uncertain.</p><p><strong>Objectives: </strong>To assess the clinical and cost-effectiveness of software fusion biopsy technologies in people with suspected localised and locally advanced prostate cancer. A systematic review was conducted to evaluate the diagnostic accuracy, clinical efficacy and practical implementation of nine software fusion devices compared to cognitive fusion biopsies, and with each other, in people with suspected prostate cancer. Comprehensive searches including MEDLINE, and Embase were conducted up to August 2022 to identify studies which compared software fusion and cognitive fusion biopsies in people with suspected prostate cancer. Risk of bias was assessed with quality assessment of diagnostic accuracy studies-comparative tool. A network meta-analysis comparing software and cognitive fusion with or without concomitant systematic biopsy, and systematic biopsy alone was conducted. Additional outcomes, including safety and usability, were synthesised narratively. A de novo decision model was developed to estimate the cost-effectiveness of targeted software fusion biopsy relative to cognitive fusion biopsy with or without concomitant systematic biopsy for prostate cancer identification in biopsy-naive people. Scenario analyses were undertaken to explore the robustness of the results to variation in the model data sources and alternative assumptions.</p><p><strong>Results: </strong>Twenty-three studies (3773 patients with software fusion, 2154 cognitive fusion) were included, of which 13 informed the main meta-analyses. Evidence was available for seven of the nine fusion devices specified in the protocol and at high risk of bias. The meta-analyses show that patients undergoing software fusion biopsy may have: (1) a lower probability of being classified as not having cancer, (2) similar probability of being classified as having non-clinically significant cancer (International Society of Urological Pathology grade 1) and (3) higher probability of being classified at higher International Society of Urological Pathology grades, particularly International Society of Urological Pathology 2. Similar results were obtained when comparing between same biopsy methods where both were combined with systematic biopsy. Evidence was insufficient to conclude whether any individual devices were superior to cognitive fusion, or whether some software fusion technologi","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 61","pages":"1-310"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377785","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}
Hollie Birkinshaw, Claire Friedrich, Peter Cole, Christopher Eccleston, Marc Serfaty, Gavin Stewart, Simon White, Andrew Moore, David Phillippo, Tamar Pincus
<p><strong>Background: </strong>Chronic pain is common and costly. Antidepressants are prescribed to reduce pain. However, there has not been a network meta-analysis examining all antidepressants across all chronic pain conditions, so effectiveness and safety for most antidepressants for pain conditions remain unknown.</p><p><strong>Objective: </strong>To assess the efficacy and safety of antidepressants for chronic pain (except headache) in adults. Our primary outcomes were as follows: substantial pain relief (50%), pain intensity, mood and adverse events. Our secondary outcomes were as follows: moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change, serious adverse events and withdrawal.</p><p><strong>Design: </strong>This was a systematic review with a network meta-analysis. We searched CENTRAL, MEDLINE, EMBASE, CINAHL, LILACS, AMED and PsycINFO databases for randomised controlled trials of antidepressants for chronic pain conditions up until 4 January 2022. The review was registered in PROSPERO (CRD42020171855), and the protocol was published in the Cochrane Library (https://doi.org/10.1002/14651858.CD014682).</p><p><strong>Setting: </strong>We analysed trials from all settings.</p><p><strong>Participants: </strong>We included trials in which participants had chronic pain, defined as longer than 3 months, from any condition excluding headache.</p><p><strong>Interventions: </strong>We included all antidepressants.</p><p><strong>Main outcome measures: </strong>Our primary outcome was substantial pain relief, defined as a reduction ˃ 50%. We also measured pain intensity, mood and adverse events. Secondary measures included moderate pain relief (above 30% reduction), physical function, sleep, quality of life, Global Impression of Change, serious adverse events, and withdrawal from trial.</p><p><strong>Results: </strong>We identified 176 studies with a total of 28,664 participants. Most studies were placebo-controlled (<i>n</i> = 83) and parallel armed (<i>n</i> = 141). The most common pain conditions examined were fibromyalgia (59 studies), neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of randomised controlled trials was 10 weeks. Most studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. Standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that for duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain.</p><p><strong>Limitations: </strong>The evidence for antidepressants other than duloxetine is poor. For duloxetine, it is not clea
{"title":"Antidepressants for pain management in adults with chronic pain: a network meta-analysis.","authors":"Hollie Birkinshaw, Claire Friedrich, Peter Cole, Christopher Eccleston, Marc Serfaty, Gavin Stewart, Simon White, Andrew Moore, David Phillippo, Tamar Pincus","doi":"10.3310/MKRT2948","DOIUrl":"10.3310/MKRT2948","url":null,"abstract":"<p><strong>Background: </strong>Chronic pain is common and costly. Antidepressants are prescribed to reduce pain. However, there has not been a network meta-analysis examining all antidepressants across all chronic pain conditions, so effectiveness and safety for most antidepressants for pain conditions remain unknown.</p><p><strong>Objective: </strong>To assess the efficacy and safety of antidepressants for chronic pain (except headache) in adults. Our primary outcomes were as follows: substantial pain relief (50%), pain intensity, mood and adverse events. Our secondary outcomes were as follows: moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change, serious adverse events and withdrawal.</p><p><strong>Design: </strong>This was a systematic review with a network meta-analysis. We searched CENTRAL, MEDLINE, EMBASE, CINAHL, LILACS, AMED and PsycINFO databases for randomised controlled trials of antidepressants for chronic pain conditions up until 4 January 2022. The review was registered in PROSPERO (CRD42020171855), and the protocol was published in the Cochrane Library (https://doi.org/10.1002/14651858.CD014682).</p><p><strong>Setting: </strong>We analysed trials from all settings.</p><p><strong>Participants: </strong>We included trials in which participants had chronic pain, defined as longer than 3 months, from any condition excluding headache.</p><p><strong>Interventions: </strong>We included all antidepressants.</p><p><strong>Main outcome measures: </strong>Our primary outcome was substantial pain relief, defined as a reduction ˃ 50%. We also measured pain intensity, mood and adverse events. Secondary measures included moderate pain relief (above 30% reduction), physical function, sleep, quality of life, Global Impression of Change, serious adverse events, and withdrawal from trial.</p><p><strong>Results: </strong>We identified 176 studies with a total of 28,664 participants. Most studies were placebo-controlled (<i>n</i> = 83) and parallel armed (<i>n</i> = 141). The most common pain conditions examined were fibromyalgia (59 studies), neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of randomised controlled trials was 10 weeks. Most studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. Standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that for duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain.</p><p><strong>Limitations: </strong>The evidence for antidepressants other than duloxetine is poor. For duloxetine, it is not clea","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 62","pages":"1-155"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11474957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377786","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}
Kylie M Gray, Magdalena M Apanasionok, Emma Scripps, Karen Bunning, Christine Burke, Malwina Filipczuk, Richard P Hastings, Ashley Liew, Rachel McNamara, Atiyya Nisar, Rebecca Playle, Tim Williams, Peter E Langdon
<p><strong>Background: </strong>There is a lack of interventions for specific phobia in children and adolescents with moderate to severe intellectual disabilities.</p><p><strong>Objectives: </strong>The objectives were to: (a) develop an intervention for specific phobia, together with an intervention fidelity checklist and logic model, and evaluate candidate outcome measures, together with parents/carers and clinicians; (b) describe treatment as usual; (c) model the intervention to determine the acceptability and feasibility for all stakeholders, judge the appropriateness of outcome measures, explore recruitment pathways, and examine the feasibility and acceptability of consent and associated processes; and (d) describe factors that facilitate or challenge the intervention.</p><p><strong>Design: </strong>Phase 1a: using consensus methods, an Intervention Development Group was established who met to develop the intervention, review candidate outcome measures and contribute to the development of the intervention fidelity checklists and logic model. Phase 1b: a national online survey was conducted with parents and professionals to describe treatment as usual. Phase 2: a single-group non-randomised feasibility study was designed to model the intervention and to test intervention feasibility and acceptability, outcome measures and aspects of the research process.</p><p><strong>Setting: </strong>Phase 2: participants were recruited from National Health Service community child learning disabilities teams and special schools in England. Treatment was delivered in the child learning disabilities teams.</p><p><strong>Participants: </strong>Children aged 5-15 years with moderate to severe learning disability and specific phobia, and their parents/carers.</p><p><strong>Interventions: </strong>The SPIRIT intervention comprised two half-day workshops and eight support sessions plus treatment as usual.</p><p><strong>Main outcomes: </strong>The feasibility and acceptability of the intervention and research processes, recruitment, outcome measure completion rates and acceptability, and intervention adherence. Parents completed all of the outcome measures, with very low rates of missing data. The recruitment of sites and participants was impacted by the COVID-19 pandemic.</p><p><strong>Results: </strong>The intervention was successfully developed and modelled with 15 participants with moderate to severe learning disabilities and their parents. The intervention was judged to be feasible and acceptable by parents/carers and therapists. Parents/carers and therapists suggested minor intervention revisions.</p><p><strong>Limitations: </strong>Randomisation was not modelled within this feasibility study, although the majority of parents and therapists indicated that this would be acceptable.</p><p><strong>Conclusions: </strong>The SPIRIT intervention and associated study processes were judged to be feasible and acceptable. The intervention requires minor revisions.</p><
{"title":"Specific phobias in children with moderate to severe intellectual disabilities: SPIRIT, an adaptation and feasibility study.","authors":"Kylie M Gray, Magdalena M Apanasionok, Emma Scripps, Karen Bunning, Christine Burke, Malwina Filipczuk, Richard P Hastings, Ashley Liew, Rachel McNamara, Atiyya Nisar, Rebecca Playle, Tim Williams, Peter E Langdon","doi":"10.3310/LRWD7852","DOIUrl":"10.3310/LRWD7852","url":null,"abstract":"<p><strong>Background: </strong>There is a lack of interventions for specific phobia in children and adolescents with moderate to severe intellectual disabilities.</p><p><strong>Objectives: </strong>The objectives were to: (a) develop an intervention for specific phobia, together with an intervention fidelity checklist and logic model, and evaluate candidate outcome measures, together with parents/carers and clinicians; (b) describe treatment as usual; (c) model the intervention to determine the acceptability and feasibility for all stakeholders, judge the appropriateness of outcome measures, explore recruitment pathways, and examine the feasibility and acceptability of consent and associated processes; and (d) describe factors that facilitate or challenge the intervention.</p><p><strong>Design: </strong>Phase 1a: using consensus methods, an Intervention Development Group was established who met to develop the intervention, review candidate outcome measures and contribute to the development of the intervention fidelity checklists and logic model. Phase 1b: a national online survey was conducted with parents and professionals to describe treatment as usual. Phase 2: a single-group non-randomised feasibility study was designed to model the intervention and to test intervention feasibility and acceptability, outcome measures and aspects of the research process.</p><p><strong>Setting: </strong>Phase 2: participants were recruited from National Health Service community child learning disabilities teams and special schools in England. Treatment was delivered in the child learning disabilities teams.</p><p><strong>Participants: </strong>Children aged 5-15 years with moderate to severe learning disability and specific phobia, and their parents/carers.</p><p><strong>Interventions: </strong>The SPIRIT intervention comprised two half-day workshops and eight support sessions plus treatment as usual.</p><p><strong>Main outcomes: </strong>The feasibility and acceptability of the intervention and research processes, recruitment, outcome measure completion rates and acceptability, and intervention adherence. Parents completed all of the outcome measures, with very low rates of missing data. The recruitment of sites and participants was impacted by the COVID-19 pandemic.</p><p><strong>Results: </strong>The intervention was successfully developed and modelled with 15 participants with moderate to severe learning disabilities and their parents. The intervention was judged to be feasible and acceptable by parents/carers and therapists. Parents/carers and therapists suggested minor intervention revisions.</p><p><strong>Limitations: </strong>Randomisation was not modelled within this feasibility study, although the majority of parents and therapists indicated that this would be acceptable.</p><p><strong>Conclusions: </strong>The SPIRIT intervention and associated study processes were judged to be feasible and acceptable. The intervention requires minor revisions.</p><","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 64","pages":"1-118"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377787","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}
Sue Harnan, Ben Kearns, Alison Scope, Laetitia Schmitt, Dina Jankovic, Jean Hamilton, Tushar Srivastava, Harry Hill, Chu Chang Ku, Shijie Ren, Claire Rothery, Laura Bojke, Mark Sculpher, Beth Woods
<p><strong>Background: </strong>To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of ceftazidime-avibactam in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England.</p><p><strong>Methods: </strong>The health benefit of ceftazidime-avibactam was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients' mortality risks and health-related quality of life. Patient-level costs and health-related quality of life of ceftazidime-avibactam under various usage scenarios compared with alternative management strategies in the high-value clinical scenarios were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population in quality-adjusted life-years using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for ceftazidime-avibactam.</p><p><strong>Results: </strong>The clinical effectiveness of ceftazidime-avibactam relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. In the base case, ceftazidime-avibactam was associated with a statistically significantly higher susceptibility relative to colistin (odds ratio 7.24, 95% credible interval 2.58 to 20.94). The remainder of the treatments were associated with lower susceptibility than colistin (odds ratio < 1). The results were sensitive to the definition of resistance and the studies included in the analysis. In the base case, patient-level benefit of ceftazidime-avibactam was between 0.08 and 0.16 quality-adjusted life-years, depending on the site of infection and the usage scenario. There was a high degree of uncertainty surrounding the benefits of ceftazidime-avibactam across all subgroups, and the results were sensitive to assumptions in the meta-analysis used to estimate susceptibility. There was substantial uncertainty in the number of infections that are suitable for treatment with ceftazidime-avibactam, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time, and rates of emergence of resistance. The population-level benefit varied substantially across
背景：为了限制抗菌药物的使用，同时又不抑制新型抗菌药物的开发，人们有兴趣建立创新模式，根据抗菌药物的价值评估而不是使用量来资助抗菌药物。该项目的目的是评估头孢唑肟-阿维巴坦在英格兰国家医疗服务体系中用于治疗严重需氧革兰阴性菌感染时，在其许可适应症范围内的人群健康效益。研究结果为英国国家健康与护理卓越研究所（National Institute for Health and Care Excellence）提供了指导，以支持生产商与英国国家医疗服务体系（NHS England）就合同价值进行商业讨论：方法：首先针对一系列高价值临床方案得出头孢唑肟-阿维巴坦的健康效益。这些方案代表了预计会对患者死亡率风险和健康相关生活质量产生重大影响的用途。使用决策模型对头孢他啶-阿维巴坦在不同使用情况下的患者层面成本和健康相关生活质量进行量化，并与高价值临床方案中的替代管理策略进行比较。结果以质量调整生命年表示的增量净健康效应进行报告，并根据英格兰公共卫生部门的数据进行感染人数预测，以质量调整生命年表示的增量净健康效应按20年人口进行缩放。高价值临床方案的估计结果被外推至头孢他啶-阿维巴坦的其他预期用途：通过网络荟萃分析，综合相关病原体对抗菌药物敏感性的证据，估算出头孢他啶-阿维巴坦相对于同类药物的临床疗效。在基础病例中，头孢唑肟-阿维巴坦相对于可乐定的敏感性在统计学上明显更高（几率比 7.24，95% 可信区间 2.58 至 20.94）。其余治疗方法的敏感性均低于可乐定（几率比小于 1）。结果对耐药性的定义和纳入分析的研究很敏感。在基础病例中，头孢他啶-阿维巴坦在患者层面的获益为0.08至0.16质量调整生命年，具体取决于感染部位和使用方案。头孢他啶-阿维巴坦在所有亚组中的获益具有高度不确定性，其结果对用于估计易感性的荟萃分析中的假设非常敏感。适合使用头孢他啶-阿维巴坦治疗的感染病例数存在很大的不确定性，因此，本文针对当前感染病例数、随着时间推移感染病例数的预期增长以及耐药性的出现率等一系列假设，给出了人群水平的结果。不同情景下的人群获益差异很大，20 年间质量调整生命年从 531 年到 2342 年不等：这项研究对头孢他啶-阿维巴坦在国民保健服务体系中的预期使用范围内的价值进行了量化估算：局限性：鉴于现有证据，头孢他啶-阿维巴坦的价值估算具有高度不确定性：今后的工作：改进 NHS 数据链接、研究支持药敏性研究的适当综合、应用常规数据和决策建模评估启用价值，都将有利于今后的抗菌药物评估工作：本研究未进行注册：本奖项由国家健康与护理研究所（NIHR）政策研究计划（NIHR奖项编号：NIHR135592）资助，通过健康与社会护理干预措施经济评估方法政策研究组（PR-PRU-1217-20401）进行，全文发表于《健康技术评估》（Health Technology Assessment）；第28卷，第73期。欲了解更多奖项信息，请访问 NIHR Funding and Awards 网站。
{"title":"Ceftazidime with avibactam for treating severe aerobic Gram-negative bacterial infections: technology evaluation to inform a novel subscription-style payment model.","authors":"Sue Harnan, Ben Kearns, Alison Scope, Laetitia Schmitt, Dina Jankovic, Jean Hamilton, Tushar Srivastava, Harry Hill, Chu Chang Ku, Shijie Ren, Claire Rothery, Laura Bojke, Mark Sculpher, Beth Woods","doi":"10.3310/YAPL9347","DOIUrl":"https://doi.org/10.3310/YAPL9347","url":null,"abstract":"<p><strong>Background: </strong>To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of ceftazidime-avibactam in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England.</p><p><strong>Methods: </strong>The health benefit of ceftazidime-avibactam was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients' mortality risks and health-related quality of life. Patient-level costs and health-related quality of life of ceftazidime-avibactam under various usage scenarios compared with alternative management strategies in the high-value clinical scenarios were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population in quality-adjusted life-years using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for ceftazidime-avibactam.</p><p><strong>Results: </strong>The clinical effectiveness of ceftazidime-avibactam relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. In the base case, ceftazidime-avibactam was associated with a statistically significantly higher susceptibility relative to colistin (odds ratio 7.24, 95% credible interval 2.58 to 20.94). The remainder of the treatments were associated with lower susceptibility than colistin (odds ratio < 1). The results were sensitive to the definition of resistance and the studies included in the analysis. In the base case, patient-level benefit of ceftazidime-avibactam was between 0.08 and 0.16 quality-adjusted life-years, depending on the site of infection and the usage scenario. There was a high degree of uncertainty surrounding the benefits of ceftazidime-avibactam across all subgroups, and the results were sensitive to assumptions in the meta-analysis used to estimate susceptibility. There was substantial uncertainty in the number of infections that are suitable for treatment with ceftazidime-avibactam, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time, and rates of emergence of resistance. The population-level benefit varied substantially across","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 73","pages":"1-230"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hosein Shabaninejad, Ryan Pw Kenny, Tomos Robinson, Akvile Stoniute, Hannah O'Keefe, Madeleine Still, Christopher Thornton, Fiona Pearson, Fiona Beyer, Nick Meader
<p><strong>Background: </strong>Neonates with suspected sepsis are commonly treated with gentamicin, an aminoglycoside. These antibiotics are associated with high risk of ototoxicity, including profound bilateral deafness, in people with the m.1555A>G mitochondrial genetic variant.</p><p><strong>Objective: </strong>This early value assessment summarised and critically assessed the clinical effectiveness and cost-effectiveness of the Genedrive MT-RNR1 ID Kit for identifying the gene m.1555A>G variant in neonates and mothers of neonates needing antibiotics or anticipated to need antibiotics. Following feedback from the scoping workshop and specialist assessment subgroup meeting, we also considered the Genedrive MT-RNR1 ID Kit for identifying the m.1555A>G variant in mothers prior to giving birth.</p><p><strong>Data sources: </strong>For clinical effectiveness, we searched three major databases in October 2022: MEDLINE, EMBASE and CINAHL (Cumulative Index to Nursing and Allied Health Literature). For cost-effectiveness, in addition to the three mentioned databases we searched Cochrane and RePEc-IDEAS.</p><p><strong>Study selection: </strong>Study selection and risk-of-bias assessment were conducted by two independent reviewers (Ryan PW Kenny and Akvile Stoniute for clinical effectiveness and Hosein Shabaninejad and Tomos Robinson for cost-effectiveness). Any differences were resolved through discussion, or by a third reviewer (Nick Meader).</p><p><strong>Study appraisal: </strong>Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. One study (<i>n</i> = 751 neonates recruited) was included in the clinical effectiveness review and no studies were included in the cost-effectiveness review. All except one outcome (test failure rate: low risk of bias) were rated as being at moderate risk of bias. The study reported accuracy of the test (sensitivity 100%, 95% confidence interval 29.2% to 100%; specificity 99.2%, 95% confidence interval 98% to 99.7%), number of neonates successfully tested (<i>n</i> = 424/526 admissions), test failure rate (17.1%, although this was reduced to 5.7%), impact on antibiotic use (all those with a m.1555A>G genotype avoided aminoglycosides), time taken to obtain a sample (6 minutes), time to genotyping (26 minutes), time to antibiotic treatment (55.18 minutes) and the number of neonates with m.1555A>G (<i>n</i> = 3).</p><p><strong>Limitations: </strong>The economic component of this work identified key evidence gaps for which further data are required before a robust economic evaluation can be conducted. These include the sensitivity of the Genedrive MT-RNR1 ID Kit for identifying the gene m.1555A>G variant in neonates, the magnitude of risk for aminoglycoside-induced hearing loss in neonates with m.1555A>G, and the prevalence of the m.1555A>G variant. Other potentially important gaps include how data regarding maternal inheritance may potentially be used in the clinical pathway.</p><p><strong>Co
{"title":"Genedrive kit for detecting single nucleotide polymorphism m.1555A>G in neonates and their mothers: a systematic review and cost-effectiveness analysis.","authors":"Hosein Shabaninejad, Ryan Pw Kenny, Tomos Robinson, Akvile Stoniute, Hannah O'Keefe, Madeleine Still, Christopher Thornton, Fiona Pearson, Fiona Beyer, Nick Meader","doi":"10.3310/TGAC4201","DOIUrl":"https://doi.org/10.3310/TGAC4201","url":null,"abstract":"<p><strong>Background: </strong>Neonates with suspected sepsis are commonly treated with gentamicin, an aminoglycoside. These antibiotics are associated with high risk of ototoxicity, including profound bilateral deafness, in people with the m.1555A>G mitochondrial genetic variant.</p><p><strong>Objective: </strong>This early value assessment summarised and critically assessed the clinical effectiveness and cost-effectiveness of the Genedrive MT-RNR1 ID Kit for identifying the gene m.1555A>G variant in neonates and mothers of neonates needing antibiotics or anticipated to need antibiotics. Following feedback from the scoping workshop and specialist assessment subgroup meeting, we also considered the Genedrive MT-RNR1 ID Kit for identifying the m.1555A>G variant in mothers prior to giving birth.</p><p><strong>Data sources: </strong>For clinical effectiveness, we searched three major databases in October 2022: MEDLINE, EMBASE and CINAHL (Cumulative Index to Nursing and Allied Health Literature). For cost-effectiveness, in addition to the three mentioned databases we searched Cochrane and RePEc-IDEAS.</p><p><strong>Study selection: </strong>Study selection and risk-of-bias assessment were conducted by two independent reviewers (Ryan PW Kenny and Akvile Stoniute for clinical effectiveness and Hosein Shabaninejad and Tomos Robinson for cost-effectiveness). Any differences were resolved through discussion, or by a third reviewer (Nick Meader).</p><p><strong>Study appraisal: </strong>Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. One study (<i>n</i> = 751 neonates recruited) was included in the clinical effectiveness review and no studies were included in the cost-effectiveness review. All except one outcome (test failure rate: low risk of bias) were rated as being at moderate risk of bias. The study reported accuracy of the test (sensitivity 100%, 95% confidence interval 29.2% to 100%; specificity 99.2%, 95% confidence interval 98% to 99.7%), number of neonates successfully tested (<i>n</i> = 424/526 admissions), test failure rate (17.1%, although this was reduced to 5.7%), impact on antibiotic use (all those with a m.1555A>G genotype avoided aminoglycosides), time taken to obtain a sample (6 minutes), time to genotyping (26 minutes), time to antibiotic treatment (55.18 minutes) and the number of neonates with m.1555A>G (<i>n</i> = 3).</p><p><strong>Limitations: </strong>The economic component of this work identified key evidence gaps for which further data are required before a robust economic evaluation can be conducted. These include the sensitivity of the Genedrive MT-RNR1 ID Kit for identifying the gene m.1555A>G variant in neonates, the magnitude of risk for aminoglycoside-induced hearing loss in neonates with m.1555A>G, and the prevalence of the m.1555A>G variant. Other potentially important gaps include how data regarding maternal inheritance may potentially be used in the clinical pathway.</p><p><strong>Co","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 75","pages":"1-75"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nick Lansdale, Kerry Woolfall, Elizabeth Deja, Tracy Mitchell, Graciaa Singhal, Raphael Goldacre, Rema Ramakrishnan, Nigel Hall, Cheryl Battersby, Chris Gale, Gareth Penman, Marian Knight, Kayleigh Stanbury, Madeleine Hurd, David Murray, Louise Linsell, Pollyanna Hardy
<p><strong>Background: </strong>Neonates undergoing emergency abdominal surgery frequently require a stoma; closing this stoma with a second operation is an essential part of recovery. Timing of closure varies. Optimal timing is unclear and would be best resolved through a randomised controlled trial; such a trial is likely to be challenging.</p><p><strong>Aim: </strong>To determine if it is feasible to conduct a clinical trial comparing 'early' versus 'late' stoma closure in neonates.</p><p><strong>Design: </strong>Mixed methods comprising three parallel workstreams incorporating: a clinician survey, prospective observational cohort study, parent interviews, focus groups, database analyses and consensus meeting.</p><p><strong>Setting: </strong>Specialist neonatal surgical centres across the United Kingdom.</p><p><strong>Participants and data sources: </strong>Neonatologists, neonatal surgeons, neonatal dietitians and neonatal nurses who care for neonates with stomas. Neonates with recent stoma, their parents and the clinicians looking after them. Three existing, overlapping clinical databases.</p><p><strong>Results: </strong>One hundred and sixty-six professionals from all 27 neonatal surgical centres completed the survey: 6 weeks was the most common target time for stoma closure across clinical scenarios, although there was wide variation. Timing of closure was influenced by nutrition, growth and stoma complications. The prospective cohort study enrolled 56 infants from 8 centres. Infants were mostly preterm with necrotising enterocolitis or intestinal perforation. Clinicians identified extreme preterm gestation and clinical conditions as reasons for not randomising babies into a hypothetical trial comparing early and late stoma closure. Parents and healthcare professionals identified that comparator arms needed more clinical flexibility in relation to timing of stoma closure. Analysis of existing databases revealed wide variation in current timing of stoma closure in neonates and identified approximately 300 eligible infants for a trial per annum in the United Kingdom.</p><p><strong>Conclusions: </strong>A trial of 'early' compared to 'late' stoma closure in neonates is feasible and is important to families and health professionals. The population of eligible babies in the United Kingdom is sufficient for such a trial. Challenges centre around lack of equipoise in certain scenarios, specifically: extremely preterm infants; infants waiting too long for stoma closure in the 'late' comparator; and logistical issues in closing a stoma at a trial-allocated time. These challenges are addressable by incorporating flexibility based on gestation at birth, communicating that both trial arms are standard practice and valid treatment options, and providing resources, for example, for operating lists.</p><p><strong>Future work: </strong>We recommend the following population, intervention, comparator and outcome as a starting point to inform future trial de
{"title":"Timing of Stoma Closure in Neonates: the ToSCiN mixed-methods study.","authors":"Nick Lansdale, Kerry Woolfall, Elizabeth Deja, Tracy Mitchell, Graciaa Singhal, Raphael Goldacre, Rema Ramakrishnan, Nigel Hall, Cheryl Battersby, Chris Gale, Gareth Penman, Marian Knight, Kayleigh Stanbury, Madeleine Hurd, David Murray, Louise Linsell, Pollyanna Hardy","doi":"10.3310/JFBC1893","DOIUrl":"https://doi.org/10.3310/JFBC1893","url":null,"abstract":"<p><strong>Background: </strong>Neonates undergoing emergency abdominal surgery frequently require a stoma; closing this stoma with a second operation is an essential part of recovery. Timing of closure varies. Optimal timing is unclear and would be best resolved through a randomised controlled trial; such a trial is likely to be challenging.</p><p><strong>Aim: </strong>To determine if it is feasible to conduct a clinical trial comparing 'early' versus 'late' stoma closure in neonates.</p><p><strong>Design: </strong>Mixed methods comprising three parallel workstreams incorporating: a clinician survey, prospective observational cohort study, parent interviews, focus groups, database analyses and consensus meeting.</p><p><strong>Setting: </strong>Specialist neonatal surgical centres across the United Kingdom.</p><p><strong>Participants and data sources: </strong>Neonatologists, neonatal surgeons, neonatal dietitians and neonatal nurses who care for neonates with stomas. Neonates with recent stoma, their parents and the clinicians looking after them. Three existing, overlapping clinical databases.</p><p><strong>Results: </strong>One hundred and sixty-six professionals from all 27 neonatal surgical centres completed the survey: 6 weeks was the most common target time for stoma closure across clinical scenarios, although there was wide variation. Timing of closure was influenced by nutrition, growth and stoma complications. The prospective cohort study enrolled 56 infants from 8 centres. Infants were mostly preterm with necrotising enterocolitis or intestinal perforation. Clinicians identified extreme preterm gestation and clinical conditions as reasons for not randomising babies into a hypothetical trial comparing early and late stoma closure. Parents and healthcare professionals identified that comparator arms needed more clinical flexibility in relation to timing of stoma closure. Analysis of existing databases revealed wide variation in current timing of stoma closure in neonates and identified approximately 300 eligible infants for a trial per annum in the United Kingdom.</p><p><strong>Conclusions: </strong>A trial of 'early' compared to 'late' stoma closure in neonates is feasible and is important to families and health professionals. The population of eligible babies in the United Kingdom is sufficient for such a trial. Challenges centre around lack of equipoise in certain scenarios, specifically: extremely preterm infants; infants waiting too long for stoma closure in the 'late' comparator; and logistical issues in closing a stoma at a trial-allocated time. These challenges are addressable by incorporating flexibility based on gestation at birth, communicating that both trial arms are standard practice and valid treatment options, and providing resources, for example, for operating lists.</p><p><strong>Future work: </strong>We recommend the following population, intervention, comparator and outcome as a starting point to inform future trial de","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 71","pages":"1-130"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peter E Langdon, Magdalena M Apanasionok, Emma Scripps, Karen Bunning, Malwina Filipczuk, David Gillespie, Richard P Hastings, Andrew Jahoda, Rachel McNamara, Dheeraj Rai, Kylie M Gray
<p><strong>Background: </strong>Interventions for anxiety need to be adapted to meet the needs of autistic people with moderate to severe learning disabilities and successfully modelled before evidence about efficacy can be generated from clinical trials.</p><p><strong>Objectives: </strong>The objectives were to: (1) adapt a behavioural intervention for anxiety, develop an intervention fidelity checklist and logic model, and appraise candidate outcome measures, together with carers, autistic people, and clinicians, (2) characterise treatment-as-usual, (3) model the adapted intervention to determine the acceptability and feasibility for all stakeholders, judge the appropriateness of outcome measures, examine the feasibility and acceptability of consent and associated processes and (4) describe factors that facilitate or challenge intervention delivery.</p><p><strong>Design: </strong>This study had two phases. Phase 1a: using consensus methods, an intervention adaptation group was formed who met to adapt the intervention, appraise candidate outcome measures, and contribute to the development of the intervention fidelity checklists and logic model. Phase 1b: a national online survey was conducted with professionals to characterise treatment-as-usual. Phase 2: this was a single-group non-randomised feasibility study designed to model the intervention to test intervention feasibility and acceptability, outcome measures, and aspects of the research process.</p><p><strong>Setting: </strong>Participants were recruited from National Health Service community adult learning disabilities teams in England.</p><p><strong>Participants: </strong>Participants aged 16 and over with a diagnosis of autism, moderate to severe learning disabilities, an anxiety disorder, and a carer who was available to take part in the intervention. For those who lacked capacity to make a decision about taking part, a consultee had to provide advice that the participant should be included in the study.</p><p><strong>Interventions: </strong>The intervention comprised 12 sessions alongside treatment-as-usual.</p><p><strong>Main outcome measures: </strong>The feasibility and acceptability of the intervention and research processes, outcome measure completion rates, and intervention adherence.</p><p><strong>Results: </strong>The intervention was successfully adapted and modelled with 28 autistic participants with moderate to severe learning disabilities. The intervention was judged to be feasible and acceptable by autistic adults with learning disabilities, carers, and therapists. Carers and therapists suggested minor intervention revisions. Carers completed 100% of outcome measures and the missing data rate was low; however, they indicated that some of the questions were repetitive and said they had difficulty responding to some items. The use of the Mental Capacity Act, 2005, led to an average 5-week delay to participant enrolment. The accrual rate was affected by the COVID-19 pandemic
{"title":"Behavioural interventions to treat anxiety in adults with autism and moderate to severe intellectual disabilities: the BEAMS-ID feasibility study.","authors":"Peter E Langdon, Magdalena M Apanasionok, Emma Scripps, Karen Bunning, Malwina Filipczuk, David Gillespie, Richard P Hastings, Andrew Jahoda, Rachel McNamara, Dheeraj Rai, Kylie M Gray","doi":"10.3310/MWTQ5721","DOIUrl":"https://doi.org/10.3310/MWTQ5721","url":null,"abstract":"<p><strong>Background: </strong>Interventions for anxiety need to be adapted to meet the needs of autistic people with moderate to severe learning disabilities and successfully modelled before evidence about efficacy can be generated from clinical trials.</p><p><strong>Objectives: </strong>The objectives were to: (1) adapt a behavioural intervention for anxiety, develop an intervention fidelity checklist and logic model, and appraise candidate outcome measures, together with carers, autistic people, and clinicians, (2) characterise treatment-as-usual, (3) model the adapted intervention to determine the acceptability and feasibility for all stakeholders, judge the appropriateness of outcome measures, examine the feasibility and acceptability of consent and associated processes and (4) describe factors that facilitate or challenge intervention delivery.</p><p><strong>Design: </strong>This study had two phases. Phase 1a: using consensus methods, an intervention adaptation group was formed who met to adapt the intervention, appraise candidate outcome measures, and contribute to the development of the intervention fidelity checklists and logic model. Phase 1b: a national online survey was conducted with professionals to characterise treatment-as-usual. Phase 2: this was a single-group non-randomised feasibility study designed to model the intervention to test intervention feasibility and acceptability, outcome measures, and aspects of the research process.</p><p><strong>Setting: </strong>Participants were recruited from National Health Service community adult learning disabilities teams in England.</p><p><strong>Participants: </strong>Participants aged 16 and over with a diagnosis of autism, moderate to severe learning disabilities, an anxiety disorder, and a carer who was available to take part in the intervention. For those who lacked capacity to make a decision about taking part, a consultee had to provide advice that the participant should be included in the study.</p><p><strong>Interventions: </strong>The intervention comprised 12 sessions alongside treatment-as-usual.</p><p><strong>Main outcome measures: </strong>The feasibility and acceptability of the intervention and research processes, outcome measure completion rates, and intervention adherence.</p><p><strong>Results: </strong>The intervention was successfully adapted and modelled with 28 autistic participants with moderate to severe learning disabilities. The intervention was judged to be feasible and acceptable by autistic adults with learning disabilities, carers, and therapists. Carers and therapists suggested minor intervention revisions. Carers completed 100% of outcome measures and the missing data rate was low; however, they indicated that some of the questions were repetitive and said they had difficulty responding to some items. The use of the Mental Capacity Act, 2005, led to an average 5-week delay to participant enrolment. The accrual rate was affected by the COVID-19 pandemic ","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 72","pages":"1-147"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Esther Crawley, Emma Anderson, Madeleine Cochrane, Beverly A Shirkey, Roxanne Parslow, William Hollingworth, Nicola Mills, Daisy Gaunt, Georgia Treneman-Evans, Manmita Rai, John Macleod, David Kessler, Kieren Pitts, Serena Cooper, Maria Loades, Ammar Annaw, Paul Stallard, Hans Knoop, Elise Van de Putte, Sanne Nijhof, Gijs Bleijenberg, Chris Metcalfe
<p><strong>Design: </strong>Parallel-group randomised controlled trial.</p><p><strong>Methods: </strong>Adolescents aged 11-17 years, diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome and with no local specialist treatment centre, were referred to a specialist service in South West England.</p><p><strong>Interventions: </strong>Fatigue In Teenagers on the interNET in the National Health Service is a web-based myalgic encephalomyelitis/chronic fatigue syndrome-focused cognitive-behavioural therapy programme for adolescents, supported by individualised written, asynchronous electronic consultations with a clinical psychologist/cognitive-behavioural therapy practitioner. The comparator was videocall-delivered activity management with a myalgic encephalomyelitis/chronic fatigue syndrome clinician. Both treatments were intended to last 6 months.</p><p><strong>Objectives: </strong>Estimate the effectiveness of Fatigue In Teenagers on the interNET in the National Health Service compared to Activity Management for paediatric myalgic encephalomyelitis/chronic fatigue syndrome. Estimate the effectiveness of Fatigue In Teenagers on the interNET in the National Health Service compared to Activity Management for those with mild/moderate comorbid mood disorders. From a National Health Service perspective, estimate the cost-effectiveness of Fatigue In Teenagers on the interNET in the National Health Service compared to Activity Management over a 12-month horizon.</p><p><strong>Primary outcome: </strong>36-item Short Form Health Survey Physical Function subscale at 6 months post randomisation.</p><p><strong>Randomisation: </strong>Web-based, using minimisation with a random component to balance allocated groups by age and gender.</p><p><strong>Blinding: </strong>While the investigators were blinded to group assignment, this was not possible for participants, parents/carers and therapists.</p><p><strong>Results: </strong>The treatment of 314 adolescents was randomly allocated, 155 to Fatigue In Teenagers on the interNET in the National Health Service. Mean age was 14 years old and 63% were female.</p><p><strong>Primary outcome: </strong>At 6 months, participants allocated to Fatigue In Teenagers on the interNET in the National Health Service were more likely to have improved physical function (mean 60.5, standard deviation 29.5, <i>n</i> = 127) compared to Activity Management (mean 50.3, standard deviation 26.5, <i>n</i> = 138). The mean difference was 8.2 (95% confidence interval 2.7 to 13.6, <i>p</i> = 0.003). The result was similar for participants meeting the National Institute for Health and Care Excellence 2021 diagnostic criteria.</p><p><strong>Secondary outcomes: </strong>Fatigue In Teenagers on the interNET in the National Health Service participants attended, on average, half a day more school per week at 6 months than those allocated Activity Management, and this difference was maintained at 12 months. There was no strong evidence that
{"title":"Comparison of cognitive behaviour therapy versus activity management, both delivered remotely, to treat paediatric chronic fatigue syndrome/myalgic encephalomyelitis: the UK FITNET-NHS RCT.","authors":"Esther Crawley, Emma Anderson, Madeleine Cochrane, Beverly A Shirkey, Roxanne Parslow, William Hollingworth, Nicola Mills, Daisy Gaunt, Georgia Treneman-Evans, Manmita Rai, John Macleod, David Kessler, Kieren Pitts, Serena Cooper, Maria Loades, Ammar Annaw, Paul Stallard, Hans Knoop, Elise Van de Putte, Sanne Nijhof, Gijs Bleijenberg, Chris Metcalfe","doi":"10.3310/VLRW6701","DOIUrl":"10.3310/VLRW6701","url":null,"abstract":"<p><strong>Design: </strong>Parallel-group randomised controlled trial.</p><p><strong>Methods: </strong>Adolescents aged 11-17 years, diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome and with no local specialist treatment centre, were referred to a specialist service in South West England.</p><p><strong>Interventions: </strong>Fatigue In Teenagers on the interNET in the National Health Service is a web-based myalgic encephalomyelitis/chronic fatigue syndrome-focused cognitive-behavioural therapy programme for adolescents, supported by individualised written, asynchronous electronic consultations with a clinical psychologist/cognitive-behavioural therapy practitioner. The comparator was videocall-delivered activity management with a myalgic encephalomyelitis/chronic fatigue syndrome clinician. Both treatments were intended to last 6 months.</p><p><strong>Objectives: </strong>Estimate the effectiveness of Fatigue In Teenagers on the interNET in the National Health Service compared to Activity Management for paediatric myalgic encephalomyelitis/chronic fatigue syndrome. Estimate the effectiveness of Fatigue In Teenagers on the interNET in the National Health Service compared to Activity Management for those with mild/moderate comorbid mood disorders. From a National Health Service perspective, estimate the cost-effectiveness of Fatigue In Teenagers on the interNET in the National Health Service compared to Activity Management over a 12-month horizon.</p><p><strong>Primary outcome: </strong>36-item Short Form Health Survey Physical Function subscale at 6 months post randomisation.</p><p><strong>Randomisation: </strong>Web-based, using minimisation with a random component to balance allocated groups by age and gender.</p><p><strong>Blinding: </strong>While the investigators were blinded to group assignment, this was not possible for participants, parents/carers and therapists.</p><p><strong>Results: </strong>The treatment of 314 adolescents was randomly allocated, 155 to Fatigue In Teenagers on the interNET in the National Health Service. Mean age was 14 years old and 63% were female.</p><p><strong>Primary outcome: </strong>At 6 months, participants allocated to Fatigue In Teenagers on the interNET in the National Health Service were more likely to have improved physical function (mean 60.5, standard deviation 29.5, <i>n</i> = 127) compared to Activity Management (mean 50.3, standard deviation 26.5, <i>n</i> = 138). The mean difference was 8.2 (95% confidence interval 2.7 to 13.6, <i>p</i> = 0.003). The result was similar for participants meeting the National Institute for Health and Care Excellence 2021 diagnostic criteria.</p><p><strong>Secondary outcomes: </strong>Fatigue In Teenagers on the interNET in the National Health Service participants attended, on average, half a day more school per week at 6 months than those allocated Activity Management, and this difference was maintained at 12 months. There was no strong evidence that ","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 70","pages":"1-134"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Inês Souto-Ribeiro, Lois Woods, Emma Maund, David Alexander Scott, Joanne Lord, Joanna Picot, Jonathan Shepherd
<p><strong>Background: </strong>People with suspected prostate cancer are usually offered either a local anaesthetic transrectal ultrasound-guided prostate biopsy or a general anaesthetic transperineal prostate biopsy. Transperineal prostate biopsy is often carried out under general anaesthetic due to pain caused by the procedure. However, recent studies suggest that performing local anaesthetic transperineal prostate biopsy may better identify cancer in particular regions of the prostate and reduce infection rates, while being carried out in an outpatient setting. Devices to assist with freehand methods of local anaesthetic transperineal prostate may also help practitioners performing prostate biopsies.</p><p><strong>Objectives: </strong>To evaluate the clinical effectiveness and cost-effectiveness of local anaesthetic transperineal prostate compared to local anaesthetic transrectal ultrasound-guided prostate and general anaesthetic transperineal prostate biopsy for people with suspected prostate cancer, and local anaesthetic transperineal prostate with specific freehand devices in comparison with local anaesthetic transrectal ultrasound-guided prostate and transperineal prostate biopsy conducted with a grid and stepping device conducted under local or general anaesthetic.</p><p><strong>Data sources and methods: </strong>We conducted a systematic review of studies comparing the diagnostic yield and clinical effectiveness of different methods for performing prostate biopsies. We used pairwise and network meta-analyses to pool evidence on cancer detection rates and structured narrative synthesis for other outcomes. For the economic evaluation, we reviewed published and submitted evidence and developed a model to assess the cost-effectiveness of the different biopsy methods.</p><p><strong>Results: </strong>We included 19 comparative studies (6 randomised controlled trials and 13 observational comparative studies) and 4 single-arm studies of freehand devices. There were no statistically significant differences in cancer detection rates for local anaesthetic transperineal prostate (any method) compared to local anaesthetic transrectal ultrasound-guided prostate (relative risk 1.00, 95% confidence interval 0.85 to 1.18) (<i>n</i> = 5 randomised controlled trials), as was the case for local anaesthetic transperineal prostate with a freehand device compared to local anaesthetic transrectal ultrasound-guided prostate (relative risk 1.40, 95% confidence interval 0.96 to 2.04) (<i>n</i> = 1 randomised controlled trial). Results of meta-analyses of observational studies were similar. The economic analysis indicated that local anaesthetic transperineal prostate is likely to be cost-effective compared with local anaesthetic transrectal ultrasound-guided prostate (incremental cost below £20,000 per quality-adjusted life-year gained) and less costly and no less effective than general anaesthetic transperineal prostate. local anaesthetic transperineal prostate w
{"title":"Transperineal biopsy devices in people with suspected prostate cancer - a systematic review and economic evaluation.","authors":"Inês Souto-Ribeiro, Lois Woods, Emma Maund, David Alexander Scott, Joanne Lord, Joanna Picot, Jonathan Shepherd","doi":"10.3310/ZKTW8214","DOIUrl":"10.3310/ZKTW8214","url":null,"abstract":"<p><strong>Background: </strong>People with suspected prostate cancer are usually offered either a local anaesthetic transrectal ultrasound-guided prostate biopsy or a general anaesthetic transperineal prostate biopsy. Transperineal prostate biopsy is often carried out under general anaesthetic due to pain caused by the procedure. However, recent studies suggest that performing local anaesthetic transperineal prostate biopsy may better identify cancer in particular regions of the prostate and reduce infection rates, while being carried out in an outpatient setting. Devices to assist with freehand methods of local anaesthetic transperineal prostate may also help practitioners performing prostate biopsies.</p><p><strong>Objectives: </strong>To evaluate the clinical effectiveness and cost-effectiveness of local anaesthetic transperineal prostate compared to local anaesthetic transrectal ultrasound-guided prostate and general anaesthetic transperineal prostate biopsy for people with suspected prostate cancer, and local anaesthetic transperineal prostate with specific freehand devices in comparison with local anaesthetic transrectal ultrasound-guided prostate and transperineal prostate biopsy conducted with a grid and stepping device conducted under local or general anaesthetic.</p><p><strong>Data sources and methods: </strong>We conducted a systematic review of studies comparing the diagnostic yield and clinical effectiveness of different methods for performing prostate biopsies. We used pairwise and network meta-analyses to pool evidence on cancer detection rates and structured narrative synthesis for other outcomes. For the economic evaluation, we reviewed published and submitted evidence and developed a model to assess the cost-effectiveness of the different biopsy methods.</p><p><strong>Results: </strong>We included 19 comparative studies (6 randomised controlled trials and 13 observational comparative studies) and 4 single-arm studies of freehand devices. There were no statistically significant differences in cancer detection rates for local anaesthetic transperineal prostate (any method) compared to local anaesthetic transrectal ultrasound-guided prostate (relative risk 1.00, 95% confidence interval 0.85 to 1.18) (<i>n</i> = 5 randomised controlled trials), as was the case for local anaesthetic transperineal prostate with a freehand device compared to local anaesthetic transrectal ultrasound-guided prostate (relative risk 1.40, 95% confidence interval 0.96 to 2.04) (<i>n</i> = 1 randomised controlled trial). Results of meta-analyses of observational studies were similar. The economic analysis indicated that local anaesthetic transperineal prostate is likely to be cost-effective compared with local anaesthetic transrectal ultrasound-guided prostate (incremental cost below £20,000 per quality-adjusted life-year gained) and less costly and no less effective than general anaesthetic transperineal prostate. local anaesthetic transperineal prostate w","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 60","pages":"1-213"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371697","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}
Alexandra Wright-Hughes, Alexander C Ford, Sarah L Alderson, Pei Loo Ow, Matthew J Ridd, Robbie Foy, Felicity L Bishop, Matthew Chaddock, Heather Cook, Deborah Cooper, Catherine Fernandez, Elspeth A Guthrie, Suzanne Hartley, Amy Herbert, Daniel Howdon, Delia P Muir, Sonia Newman, Christopher A Taylor, Emma J Teasdale, Ruth Thornton, Hazel A Everitt, Amanda J Farrin
<p><strong>Background: </strong>Irritable bowel syndrome, characterised by abdominal pain and a change in stool form or frequency, is most often managed in primary care. When first-line therapies are ineffective, National Institute for Health and Care Excellence guidelines suggest considering low-dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown and they are infrequently prescribed by general practitioners.</p><p><strong>Objective: </strong>To evaluate the clinical and cost-effectiveness of low-dose titrated amitriptyline as a second-line treatment for irritable bowel syndrome in primary care.</p><p><strong>Design: </strong>A pragmatic, randomised, multicentre, two-arm, double-blind, placebo-controlled trial. A nested, qualitative study explored participant and general practitioner experiences of treatments and trial participation, and implications for wider use of amitriptyline for irritable bowel syndrome in primary care. Participants, clinicians, investigators and analysts were masked to allocation.</p><p><strong>Setting: </strong>Fifty-five general practices in three regions in England (Wessex, West of England, West Yorkshire).</p><p><strong>Participants: </strong>Patients aged ≥ 18 years meeting Rome IV criteria for irritable bowel syndrome with ongoing symptoms after trying first-line treatments and no contraindications to TCAs.</p><p><strong>Intervention: </strong>Amitriptyline 10 mg once-daily, self-titrated by participants to a maximum of 30 mg once-daily or matched placebo for 6 months. Participants randomised 1 : 1 with most having the option to continue blinded treatment for a further 6 months.</p><p><strong>Main outcome measures: </strong>The primary participant-reported outcome was the effect of amitriptyline on global irritable bowel syndrome symptoms at 6 months, measured using the irritable bowel syndrome Severity Scoring System, with a 35-point between-group difference defined as the minimum clinically important difference. The key secondary outcome was the proportion of participants reporting subjective global assessment of relief at 6 months, defined as somewhat, considerable, or complete relief of symptoms. Other secondary outcomes included: effect on global symptoms, via the irritable bowel syndrome Severity Scoring System, and subjective global assessment of relief of irritable bowel syndrome symptoms at 3 and 12 months; effect on somatic symptom-reporting at 6 months; anxiety an-d depression scores; ability to work and participate in other activities at 3, 6 and 12 months; acceptability, tolerability and adherence to trial medication.</p><p><strong>Results: </strong>Four hundred and sixty-three participants were randomised to amitriptyline (232) or placebo (231). An intention-to-treat analysis of the primary outcome showed a significant difference in favour of amitriptyline for irritable bowel syndrome Severity Scoring System score between arms at 6 months [-27.0, 9
{"title":"Low-dose titrated amitriptyline as second-line treatment for adults with irritable bowel syndrome in primary care: the ATLANTIS RCT.","authors":"Alexandra Wright-Hughes, Alexander C Ford, Sarah L Alderson, Pei Loo Ow, Matthew J Ridd, Robbie Foy, Felicity L Bishop, Matthew Chaddock, Heather Cook, Deborah Cooper, Catherine Fernandez, Elspeth A Guthrie, Suzanne Hartley, Amy Herbert, Daniel Howdon, Delia P Muir, Sonia Newman, Christopher A Taylor, Emma J Teasdale, Ruth Thornton, Hazel A Everitt, Amanda J Farrin","doi":"10.3310/BFCR7986","DOIUrl":"10.3310/BFCR7986","url":null,"abstract":"<p><strong>Background: </strong>Irritable bowel syndrome, characterised by abdominal pain and a change in stool form or frequency, is most often managed in primary care. When first-line therapies are ineffective, National Institute for Health and Care Excellence guidelines suggest considering low-dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown and they are infrequently prescribed by general practitioners.</p><p><strong>Objective: </strong>To evaluate the clinical and cost-effectiveness of low-dose titrated amitriptyline as a second-line treatment for irritable bowel syndrome in primary care.</p><p><strong>Design: </strong>A pragmatic, randomised, multicentre, two-arm, double-blind, placebo-controlled trial. A nested, qualitative study explored participant and general practitioner experiences of treatments and trial participation, and implications for wider use of amitriptyline for irritable bowel syndrome in primary care. Participants, clinicians, investigators and analysts were masked to allocation.</p><p><strong>Setting: </strong>Fifty-five general practices in three regions in England (Wessex, West of England, West Yorkshire).</p><p><strong>Participants: </strong>Patients aged ≥ 18 years meeting Rome IV criteria for irritable bowel syndrome with ongoing symptoms after trying first-line treatments and no contraindications to TCAs.</p><p><strong>Intervention: </strong>Amitriptyline 10 mg once-daily, self-titrated by participants to a maximum of 30 mg once-daily or matched placebo for 6 months. Participants randomised 1 : 1 with most having the option to continue blinded treatment for a further 6 months.</p><p><strong>Main outcome measures: </strong>The primary participant-reported outcome was the effect of amitriptyline on global irritable bowel syndrome symptoms at 6 months, measured using the irritable bowel syndrome Severity Scoring System, with a 35-point between-group difference defined as the minimum clinically important difference. The key secondary outcome was the proportion of participants reporting subjective global assessment of relief at 6 months, defined as somewhat, considerable, or complete relief of symptoms. Other secondary outcomes included: effect on global symptoms, via the irritable bowel syndrome Severity Scoring System, and subjective global assessment of relief of irritable bowel syndrome symptoms at 3 and 12 months; effect on somatic symptom-reporting at 6 months; anxiety an-d depression scores; ability to work and participate in other activities at 3, 6 and 12 months; acceptability, tolerability and adherence to trial medication.</p><p><strong>Results: </strong>Four hundred and sixty-three participants were randomised to amitriptyline (232) or placebo (231). An intention-to-treat analysis of the primary outcome showed a significant difference in favour of amitriptyline for irritable bowel syndrome Severity Scoring System score between arms at 6 months [-27.0, 9","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 66","pages":"1-161"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463898","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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