Enoch F Akowuah, Rebecca H Maier, Helen C Hancock, Janelle Wagnild, Luke Vale, Cristina Fernandez-Garcia, Ehsan Kharati, Emmanuel Ogundimu, Ayesha Mathias, Zoe Walmsley, Nicola Howe, Richard Graham, Karen Ainsworth, Joseph Zacharias
<p><strong>Background: </strong>The safety, effectiveness and cost-effectiveness of mitral valve repair via thoracoscopically guided minithoracotomy compared with conventional median sternotomy (Sternotomy) in patients with degenerative mitral valve regurgitation is uncertain and widely debated.</p><p><strong>Objectives: </strong>To determine if Mini was more effective than Sternotomy in terms of physical functioning and associated return to usual activities and was cost-effective compared with Sternotomy.</p><p><strong>Design: </strong>A pragmatic, multicentre, expertise-based, superiority, randomised trial.</p><p><strong>Participants: </strong>Adults with degenerative mitral valve regurgitation undergoing mitral valve repair surgery.</p><p><strong>Setting: </strong>Ten tertiary care institutions in the United Kingdom.</p><p><strong>Intervention: </strong>Mini or Sternotomy mitral valve repair performed by an expert surgeon.</p><p><strong>Blinding: </strong>Primary outcome measure [Short Form 36-item Health Survey, version 2 (SF-36v2) physical functioning score] was measured by an independent assessor, blinded to allocation. Echocardiographic findings were measured in a core laboratory, blinded to allocation.</p><p><strong>Outcome measures: </strong>Primary outcomes were physical functioning and associated return to usual activities measured by change from baseline in SF-36v2 physical function domain at 12 weeks following index surgery. The primary economic measure was incremental cost per quality-adjusted life-year over the year following surgery. Secondary outcomes included recurrent mitral regurgitation grade, physical activity and quality of life measured at time points to 1 year. Safety outcomes included death, repeat mitral valve surgery or heart failure hospitalisation up to 1 year.</p><p><strong>Results: </strong>Between November 2016 and January 2021, 330 participants were randomised; 166 to Mini and 164 to Sternotomy. Of these, 309 underwent surgery and 294 reported the primary outcome. Thirty per cent were female. At 12 weeks, mean difference between groups in the change in SF-36v2 physical function <i>T</i>-scores was 0.68 (95% confidence interval -1.89 to 3.26). Valve repair rates (96%) were similar in both groups. Echocardiography demonstrated mitral regurgitation severity as none or mild for 92% of participants at 1 year in both groups. The composite safety outcome occurred in 5.4% (9/166) of Mini and 6.1% (10/163) of Sternotomy participants at 1 year. On average, Mini was more costly £29,424 (95% confidence interval 26,909 to 31,940) versus £27,397 (95% confidence interval 25,172 to 29,620) and more effective 0.81 quality-adjusted life-years (95% confidence interval 0.78 to 0.84) versus 0.78 (95% confidence interval 0.75 to 0.81) than Sternotomy. The adjusted incremental cost-effectiveness ratio was £74,863 per quality-adjusted life-year for the comparison between Mini and Sternotomy. Mini has a probability of < 50% of being cost
{"title":"Minimally invasive thoracoscopically-guided right minithoracotomy versus conventional sternotomy for mitral valve repair: the UK Mini Mitral multicentre RCT.","authors":"Enoch F Akowuah, Rebecca H Maier, Helen C Hancock, Janelle Wagnild, Luke Vale, Cristina Fernandez-Garcia, Ehsan Kharati, Emmanuel Ogundimu, Ayesha Mathias, Zoe Walmsley, Nicola Howe, Richard Graham, Karen Ainsworth, Joseph Zacharias","doi":"10.3310/PKOT2391","DOIUrl":"10.3310/PKOT2391","url":null,"abstract":"<p><strong>Background: </strong>The safety, effectiveness and cost-effectiveness of mitral valve repair via thoracoscopically guided minithoracotomy compared with conventional median sternotomy (Sternotomy) in patients with degenerative mitral valve regurgitation is uncertain and widely debated.</p><p><strong>Objectives: </strong>To determine if Mini was more effective than Sternotomy in terms of physical functioning and associated return to usual activities and was cost-effective compared with Sternotomy.</p><p><strong>Design: </strong>A pragmatic, multicentre, expertise-based, superiority, randomised trial.</p><p><strong>Participants: </strong>Adults with degenerative mitral valve regurgitation undergoing mitral valve repair surgery.</p><p><strong>Setting: </strong>Ten tertiary care institutions in the United Kingdom.</p><p><strong>Intervention: </strong>Mini or Sternotomy mitral valve repair performed by an expert surgeon.</p><p><strong>Blinding: </strong>Primary outcome measure [Short Form 36-item Health Survey, version 2 (SF-36v2) physical functioning score] was measured by an independent assessor, blinded to allocation. Echocardiographic findings were measured in a core laboratory, blinded to allocation.</p><p><strong>Outcome measures: </strong>Primary outcomes were physical functioning and associated return to usual activities measured by change from baseline in SF-36v2 physical function domain at 12 weeks following index surgery. The primary economic measure was incremental cost per quality-adjusted life-year over the year following surgery. Secondary outcomes included recurrent mitral regurgitation grade, physical activity and quality of life measured at time points to 1 year. Safety outcomes included death, repeat mitral valve surgery or heart failure hospitalisation up to 1 year.</p><p><strong>Results: </strong>Between November 2016 and January 2021, 330 participants were randomised; 166 to Mini and 164 to Sternotomy. Of these, 309 underwent surgery and 294 reported the primary outcome. Thirty per cent were female. At 12 weeks, mean difference between groups in the change in SF-36v2 physical function <i>T</i>-scores was 0.68 (95% confidence interval -1.89 to 3.26). Valve repair rates (96%) were similar in both groups. Echocardiography demonstrated mitral regurgitation severity as none or mild for 92% of participants at 1 year in both groups. The composite safety outcome occurred in 5.4% (9/166) of Mini and 6.1% (10/163) of Sternotomy participants at 1 year. On average, Mini was more costly £29,424 (95% confidence interval 26,909 to 31,940) versus £27,397 (95% confidence interval 25,172 to 29,620) and more effective 0.81 quality-adjusted life-years (95% confidence interval 0.78 to 0.84) versus 0.78 (95% confidence interval 0.75 to 0.81) than Sternotomy. The adjusted incremental cost-effectiveness ratio was £74,863 per quality-adjusted life-year for the comparison between Mini and Sternotomy. Mini has a probability of < 50% of being cost","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 55","pages":"1-121"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12666603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488547","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}
E Andrea Nelson, Colin C Everett, Henrietta Konwea, Angela Oates, Sarah T Brown, Chris Bojke, Michael Backhouse, Howard Collier, Joanna Dennett, Rachael Gilberts, Benjamin A Lipsky, Michelle M Lister, Jane Nixon, David Russell, Tim Sloan, Fran Game
<p><strong>Background: </strong>Foot ulcers affecting people with diabetes (diabetic foot ulcers) often become infected, potentially leading to amputation. Suspected diabetic foot ulcer infection is treated with immediate empiric antimicrobials, with wound samples for culture and sensitivity collected to optimise antibiotic therapy. Collecting samples with swabs is easier than obtaining tissue, but this reports fewer pathogens and more contaminants. Compared with standard culture and sensitivity laboratory methods, molecular microbiology identifies more organisms. How these differences affect clinical decisions or outcomes is currently unknown. To determine if taking tissue samples versus swabs from suspected infected diabetic foot ulcer affects ulcer healing, antibiotic prescribing, costs of care and patient safety.</p><p><strong>Substudy 1: </strong>To determine the agreement between microbiology results from culture and sensitivity versus molecular techniques and to assess whether intention of prescribers to change antimicrobials differs based on sampling methods.</p><p><strong>Substudy 2: </strong>A health-economic perspective of the expected application of empiric and/or targeted treatment regimens and the cost consequences of treatment decisions based on substudy 1.</p><p><strong>Substudy 3: </strong>To compare questionnaire response rates for theoretically informed versus standard participant letters.</p><p><strong>Substudy 4: </strong>To explore clinician perspectives on diabetic foot ulcer sampling and processing techniques.</p><p><strong>Design: </strong>Randomised controlled trial of results of performing tissue sampling versus swabbing of wounds in people with suspected mild or moderate infected diabetic foot ulcer. Individually randomised (allocation concealed), 1 : 1, tissue or swab sampling for suspected diabetic foot ulcer infection. Follow-up is 12-24 months. A priori sample size estimate is 730.</p><p><strong>Substudy 1: </strong>Cross-sectional agreement study of microbiology results from molecular versus culture and sensitivity techniques and virtual clinic. Diabetic foot ulcers sampled for standard microbiology and central laboratory analysis (molecular).</p><p><strong>Substudy 2: </strong>Exploratory cost-consequence analysis of molecular processing and the likelihood of empiric and targeted treatment based on treatment decisions from substudy 1.</p><p><strong>Substudy 3: </strong>Randomised trial of theoretically informed versus standard participant letters.</p><p><strong>Substudy 4: </strong>Qualitative study explored clinicians' perspectives regarding sampling and processing techniques.</p><p><strong>Setting and participants: </strong>Twenty-one United Kingdom diabetic foot ulcer clinics. Participants with suspected mild or moderate infected diabetic foot ulcers. Time to ulcer healing (primary outcome blinded assessment), proportion of ulcers healed, antibiotic usage, ulcer area reduction at 4 weeks, hospitalisation durat
{"title":"Swabs versus tissue samples for infected diabetic foot ulcers: the CODIFI2 RCT.","authors":"E Andrea Nelson, Colin C Everett, Henrietta Konwea, Angela Oates, Sarah T Brown, Chris Bojke, Michael Backhouse, Howard Collier, Joanna Dennett, Rachael Gilberts, Benjamin A Lipsky, Michelle M Lister, Jane Nixon, David Russell, Tim Sloan, Fran Game","doi":"10.3310/KKPP0404","DOIUrl":"10.3310/KKPP0404","url":null,"abstract":"<p><strong>Background: </strong>Foot ulcers affecting people with diabetes (diabetic foot ulcers) often become infected, potentially leading to amputation. Suspected diabetic foot ulcer infection is treated with immediate empiric antimicrobials, with wound samples for culture and sensitivity collected to optimise antibiotic therapy. Collecting samples with swabs is easier than obtaining tissue, but this reports fewer pathogens and more contaminants. Compared with standard culture and sensitivity laboratory methods, molecular microbiology identifies more organisms. How these differences affect clinical decisions or outcomes is currently unknown. To determine if taking tissue samples versus swabs from suspected infected diabetic foot ulcer affects ulcer healing, antibiotic prescribing, costs of care and patient safety.</p><p><strong>Substudy 1: </strong>To determine the agreement between microbiology results from culture and sensitivity versus molecular techniques and to assess whether intention of prescribers to change antimicrobials differs based on sampling methods.</p><p><strong>Substudy 2: </strong>A health-economic perspective of the expected application of empiric and/or targeted treatment regimens and the cost consequences of treatment decisions based on substudy 1.</p><p><strong>Substudy 3: </strong>To compare questionnaire response rates for theoretically informed versus standard participant letters.</p><p><strong>Substudy 4: </strong>To explore clinician perspectives on diabetic foot ulcer sampling and processing techniques.</p><p><strong>Design: </strong>Randomised controlled trial of results of performing tissue sampling versus swabbing of wounds in people with suspected mild or moderate infected diabetic foot ulcer. Individually randomised (allocation concealed), 1 : 1, tissue or swab sampling for suspected diabetic foot ulcer infection. Follow-up is 12-24 months. A priori sample size estimate is 730.</p><p><strong>Substudy 1: </strong>Cross-sectional agreement study of microbiology results from molecular versus culture and sensitivity techniques and virtual clinic. Diabetic foot ulcers sampled for standard microbiology and central laboratory analysis (molecular).</p><p><strong>Substudy 2: </strong>Exploratory cost-consequence analysis of molecular processing and the likelihood of empiric and targeted treatment based on treatment decisions from substudy 1.</p><p><strong>Substudy 3: </strong>Randomised trial of theoretically informed versus standard participant letters.</p><p><strong>Substudy 4: </strong>Qualitative study explored clinicians' perspectives regarding sampling and processing techniques.</p><p><strong>Setting and participants: </strong>Twenty-one United Kingdom diabetic foot ulcer clinics. Participants with suspected mild or moderate infected diabetic foot ulcers. Time to ulcer healing (primary outcome blinded assessment), proportion of ulcers healed, antibiotic usage, ulcer area reduction at 4 weeks, hospitalisation durat","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 59","pages":"1-53"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12668260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488649","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}
Helen Mossop, Sarah Al Ashmori, Tumi Sotire, Emma Clark, Gillian Watson, Miles Witham, Luke Vale, Naomi McGregor, Julia Phillipson, James Ms Wason, Alison J Yarnall, Helen Hancock, Rose Anne Kenny, James Frith
<p><strong>Background: </strong>Orthostatic hypotension is a significant drop in blood pressure upon standing upright. It is very common and can result in symptoms such as postural dizziness, fainting and falls. Within the United Kingdom National Health Service, there are three principal treatments: non-drug therapies, and two medications - fludrocortisone or midodrine. Despite this we do not know which treatments are the most effective, nor whether they are cost-effective.</p><p><strong>Objective: </strong>Evaluate the feasibility of a randomised trial to evaluate the clinical and cost-effectiveness of fludrocortisone and midodrine in comparison to non-drug therapies for the treatment of orthostatic hypotension.</p><p><strong>Design: </strong>A 10-month pilot of a pragmatic, open-label, randomised, prospective, superiority, multiarm, multistage clinical trial. The pilot evaluated recruitment, attrition, crossover and quality of outcomes.</p><p><strong>Setting: </strong>Falls and Syncope, Movement Disorder, Geriatrics, and Cardiology clinics in United Kingdom National Health Service secondary care.</p><p><strong>Participants: </strong>Adults with symptomatic orthostatic hypotension.</p><p><strong>Interventions: </strong>Control: Non-drug therapies (conservative management). Interventions: Conservative management plus fludrocortisone (50-400 mcg daily) or conservative management plus midodrine (5-30 mg daily).</p><p><strong>Main outcome measures: </strong>Recruitment: Target was 40-64 participants from 14 sites. Attrition target: ≤ 15% participants withdraw before the primary end point. Crossover: To determine the rates of crossover between intervention arms. Outcome data: Assess the quality and completeness of outcomes. Other important outcomes included feedback via questionnaire and interview from sites and participants.</p><p><strong>Results: </strong>Two hundred and eighty-two patients were screened for eligibility during the pilot; of these, 13 were recruited from 4 of 9 open sites. Current or recent use of one of the study medications accounted for 120 (52%) exclusions due to ineligibility. At the primary end point of 6 months, 10 of the 13 participants (77%) remained in the study. Of those, completion rates for primary and secondary outcomes were 100%, except for the falls diaries, which was 60%. Feedback from sites revealed that redeployment of clinical and research staff due to COVID-19 negatively impacted on site opening and screening for eligible participants. Adapting the protocol to make it more flexible for remote clinics and more pragmatic for clinical use did not improve recruitment.</p><p><strong>Limitations: </strong>The sample size is too small to provide a reliable estimate of attrition and crossover rates for future studies.</p><p><strong>Conclusions: </strong>This study was not feasible in its current design. COVID-19 had an impact on staffing and site opening, while the exclusion criteria limited recruitment.</p><p><strong>F
{"title":"Control, Fludrocortisone or Midodrine for the treatment of Orthostatic Hypotension: CONFORM-OH pilot RCT and economic evaluation.","authors":"Helen Mossop, Sarah Al Ashmori, Tumi Sotire, Emma Clark, Gillian Watson, Miles Witham, Luke Vale, Naomi McGregor, Julia Phillipson, James Ms Wason, Alison J Yarnall, Helen Hancock, Rose Anne Kenny, James Frith","doi":"10.3310/HGRW7249","DOIUrl":"10.3310/HGRW7249","url":null,"abstract":"<p><strong>Background: </strong>Orthostatic hypotension is a significant drop in blood pressure upon standing upright. It is very common and can result in symptoms such as postural dizziness, fainting and falls. Within the United Kingdom National Health Service, there are three principal treatments: non-drug therapies, and two medications - fludrocortisone or midodrine. Despite this we do not know which treatments are the most effective, nor whether they are cost-effective.</p><p><strong>Objective: </strong>Evaluate the feasibility of a randomised trial to evaluate the clinical and cost-effectiveness of fludrocortisone and midodrine in comparison to non-drug therapies for the treatment of orthostatic hypotension.</p><p><strong>Design: </strong>A 10-month pilot of a pragmatic, open-label, randomised, prospective, superiority, multiarm, multistage clinical trial. The pilot evaluated recruitment, attrition, crossover and quality of outcomes.</p><p><strong>Setting: </strong>Falls and Syncope, Movement Disorder, Geriatrics, and Cardiology clinics in United Kingdom National Health Service secondary care.</p><p><strong>Participants: </strong>Adults with symptomatic orthostatic hypotension.</p><p><strong>Interventions: </strong>Control: Non-drug therapies (conservative management). Interventions: Conservative management plus fludrocortisone (50-400 mcg daily) or conservative management plus midodrine (5-30 mg daily).</p><p><strong>Main outcome measures: </strong>Recruitment: Target was 40-64 participants from 14 sites. Attrition target: ≤ 15% participants withdraw before the primary end point. Crossover: To determine the rates of crossover between intervention arms. Outcome data: Assess the quality and completeness of outcomes. Other important outcomes included feedback via questionnaire and interview from sites and participants.</p><p><strong>Results: </strong>Two hundred and eighty-two patients were screened for eligibility during the pilot; of these, 13 were recruited from 4 of 9 open sites. Current or recent use of one of the study medications accounted for 120 (52%) exclusions due to ineligibility. At the primary end point of 6 months, 10 of the 13 participants (77%) remained in the study. Of those, completion rates for primary and secondary outcomes were 100%, except for the falls diaries, which was 60%. Feedback from sites revealed that redeployment of clinical and research staff due to COVID-19 negatively impacted on site opening and screening for eligible participants. Adapting the protocol to make it more flexible for remote clinics and more pragmatic for clinical use did not improve recruitment.</p><p><strong>Limitations: </strong>The sample size is too small to provide a reliable estimate of attrition and crossover rates for future studies.</p><p><strong>Conclusions: </strong>This study was not feasible in its current design. COVID-19 had an impact on staffing and site opening, while the exclusion criteria limited recruitment.</p><p><strong>F","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 54","pages":"1-21"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12666604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488626","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}
Kapil Sayal, Laura Wyatt, Louise Thomson, Grace Holt, Colleen Ewart, Anupam Bhardwaj, Bernadka Dubicka, Tamsin Marshall, Julia Gledhill, Alexandra Lang, Kirsty Sprange, Christopher Partlett, Kristina Newman, Sebastian Moody, Helen Bould, Clare Upton, Matthew Keane, Edward Cox, Marilyn James, Alan Montgomery
<p><strong>Background: </strong>Emotional disorders are common in children and young people and can significantly impair their quality of life. Evidence-based treatments require a timely and appropriate diagnosis. The utility of standardised diagnostic assessment tools may aid the detection of emotional disorders, but there is limited evidence of their clinical value.</p><p><strong>Objectives: </strong>To assess the clinical effectiveness and cost effectiveness of a standardised diagnostic assessment for children and young people with emotional difficulties referred to Child and Adolescent Mental Health Services. A nested qualitative process evaluation aimed to identify the barriers and facilitators to using a standardised diagnostic assessment tool in Child and Adolescent Mental Health Services.</p><p><strong>Design: </strong>A United Kingdom, multicentre, two-arm, parallel-group randomised controlled trial with a nested qualitative process evaluation.</p><p><strong>Setting: </strong>Eight National Health Service Trusts providing multidisciplinary specialist Child and Adolescent Mental Health Services.</p><p><strong>Participants: </strong>Children and young people aged 5-17 years with emotional difficulties referred to Child and Adolescent Mental Health Services, excluding emergency/urgent referrals that required an expedited assessment. In the qualitative process evaluation, 15 young people aged 16-17 years, 38 parents/carers and 56 healthcare professionals participated in semistructured interviews.</p><p><strong>Interventions: </strong>Participants were randomly assigned (1 : 1) following referral receipt to intervention (the development and well-being assessment) and usual care, or usual care only.</p><p><strong>Main outcome measures: </strong>Primary outcome was a clinician-made diagnosis decision about the presence of an emotional disorder within 12 months of randomisation, collected from Child and Adolescent Mental Health Services clinical records. Secondary outcomes collected from clinical records included referral acceptance, time to offer and start treatment/interventions and discharge. Data were also self-reported from participants through online questionnaires at baseline, 6 and 12 months post randomisation, and the cost effectiveness of the intervention was investigated.</p><p><strong>Results: </strong>One thousand two hundred and twenty-five (1225) children and young people were randomly assigned (1 : 1) to study groups between 27 August 2019 and 17 October 2021; 615 were assigned to the intervention and 610 were assigned to the control group. Adherence to the intervention (full/partial completion of the development and well-being assessment) was 80% (494/615). At 12 months, 68 (11%) participants in the intervention group received an emotional disorder diagnosis versus 72 (12%) in the control group [adjusted risk ratio 0.94 (95% confidence interval 0.70 to 1.28); <i>p</i> = 0.71]. Child and Adolescent Mental Health Services acceptan
{"title":"Clinical and cost-effectiveness of a standardised diagnostic assessment for children and adolescents with emotional difficulties: the STADIA multi-centre RCT.","authors":"Kapil Sayal, Laura Wyatt, Louise Thomson, Grace Holt, Colleen Ewart, Anupam Bhardwaj, Bernadka Dubicka, Tamsin Marshall, Julia Gledhill, Alexandra Lang, Kirsty Sprange, Christopher Partlett, Kristina Newman, Sebastian Moody, Helen Bould, Clare Upton, Matthew Keane, Edward Cox, Marilyn James, Alan Montgomery","doi":"10.3310/GJKS0519","DOIUrl":"10.3310/GJKS0519","url":null,"abstract":"<p><strong>Background: </strong>Emotional disorders are common in children and young people and can significantly impair their quality of life. Evidence-based treatments require a timely and appropriate diagnosis. The utility of standardised diagnostic assessment tools may aid the detection of emotional disorders, but there is limited evidence of their clinical value.</p><p><strong>Objectives: </strong>To assess the clinical effectiveness and cost effectiveness of a standardised diagnostic assessment for children and young people with emotional difficulties referred to Child and Adolescent Mental Health Services. A nested qualitative process evaluation aimed to identify the barriers and facilitators to using a standardised diagnostic assessment tool in Child and Adolescent Mental Health Services.</p><p><strong>Design: </strong>A United Kingdom, multicentre, two-arm, parallel-group randomised controlled trial with a nested qualitative process evaluation.</p><p><strong>Setting: </strong>Eight National Health Service Trusts providing multidisciplinary specialist Child and Adolescent Mental Health Services.</p><p><strong>Participants: </strong>Children and young people aged 5-17 years with emotional difficulties referred to Child and Adolescent Mental Health Services, excluding emergency/urgent referrals that required an expedited assessment. In the qualitative process evaluation, 15 young people aged 16-17 years, 38 parents/carers and 56 healthcare professionals participated in semistructured interviews.</p><p><strong>Interventions: </strong>Participants were randomly assigned (1 : 1) following referral receipt to intervention (the development and well-being assessment) and usual care, or usual care only.</p><p><strong>Main outcome measures: </strong>Primary outcome was a clinician-made diagnosis decision about the presence of an emotional disorder within 12 months of randomisation, collected from Child and Adolescent Mental Health Services clinical records. Secondary outcomes collected from clinical records included referral acceptance, time to offer and start treatment/interventions and discharge. Data were also self-reported from participants through online questionnaires at baseline, 6 and 12 months post randomisation, and the cost effectiveness of the intervention was investigated.</p><p><strong>Results: </strong>One thousand two hundred and twenty-five (1225) children and young people were randomly assigned (1 : 1) to study groups between 27 August 2019 and 17 October 2021; 615 were assigned to the intervention and 610 were assigned to the control group. Adherence to the intervention (full/partial completion of the development and well-being assessment) was 80% (494/615). At 12 months, 68 (11%) participants in the intervention group received an emotional disorder diagnosis versus 72 (12%) in the control group [adjusted risk ratio 0.94 (95% confidence interval 0.70 to 1.28); <i>p</i> = 0.71]. Child and Adolescent Mental Health Services acceptan","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 61","pages":"1-34"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12641346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523328","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}
Michael Richard Whitehouse, Andrew Judge, Samuel Hawley, Albert Prats Uribe, Antonella Delmestri, Gulraj Matharu, Andrew Moore, Cecily Palmer, Vikki Wylde, Edith Anderson, Richard Donovan, Catherine Jameson, Nick Snelling, Ashley W Blom, Rachael Gooberman-Hill, Karen Barker, Daniel Prieto-Alhambra
<p><strong>Background: </strong>Intra-articular corticosteroid injections are an adjunct to core treatments for osteoarthritis. The National Institute for Health and Care Research Health Technology Assessment programme commissioned this research to address uncertainty around the long-term benefits and potential risks associated with recurrent intra-articular corticosteroid injections.</p><p><strong>Objectives: </strong>Characterise current intra-articular corticosteroid injection practice. Establish longer-term effects and safety of single and recurrent intra-articular corticosteroid injections. Explore views and experiences of patients and clinicians. Assess the priorities/feasibility for future research.</p><p><strong>Methods: </strong>A cohort study of incident osteoarthritis patients (2005-20) was performed using United Kingdom primary care data (Clinical Practice Research Datalink) linked to hospital data (Hospital Episode Statistics). Incidence of first intra-articular corticosteroid injection was stratified by age, calendar year, gender and geographical region. Longer-term outcomes included incident pain medication and joint replacement. Instrumental variables based on practice preference for intra-articular corticosteroid injection were used in primary analyses. Safety was assessed with propensity score matching and a self-controlled cohort, with outcomes (mortality, bleeding, hemarthrosis, wound infection, diabetes, stroke, ischaemic heart disease, myocardial infarction) assessed at 6 months. Semistructured telephone/videocall interviews were conducted (patients = 38, primary care clinicians = 19), with inductive thematic analysis used to investigate views and experiences of intra-articular corticosteroid injections. A three-round modified Delphi study with patients (<i>n</i> = 41), healthcare professionals (<i>n</i> = 25) and academics/researchers (<i>n</i> = 25) was performed to identify future primary research priorities and feasibility.</p><p><strong>Results: </strong>There were 23,899 (10.8%) osteoarthritis patients receiving intra-articular corticosteroid injections (40% received > 1 injection). Incidence of intra-articular corticosteroid injection at 5-year follow-up was lowest for elbow (5.2%) and highest for shoulder (13.6%). Incidences remained stable for all joints between 2005 and 2019 but varied between regions {3.8 [95% confidence interval 3.4 to 4.1] to 1.4 [95% confidence interval 1.3 to 1.5] injections per 100 patient-years}. Intra-articular corticosteroid injection for knee osteoarthritis was associated with lower incident use of several pain medications at 5-year follow-up; recurrent knee intra-articular corticosteroid injections were associated with greater risk reduction. In primary analyses intra-articular corticosteroid injection was associated with a lower 5-year cumulative incidence of knee replacement (number needed to treat 17, 95% confidence interval 12 to 40), but not hip replacement. In certain analyses, inc
{"title":"RecUrrent Intra-articular Corticosteroid injections in Osteoarthritis: the RUbICOn mixed-methods study.","authors":"Michael Richard Whitehouse, Andrew Judge, Samuel Hawley, Albert Prats Uribe, Antonella Delmestri, Gulraj Matharu, Andrew Moore, Cecily Palmer, Vikki Wylde, Edith Anderson, Richard Donovan, Catherine Jameson, Nick Snelling, Ashley W Blom, Rachael Gooberman-Hill, Karen Barker, Daniel Prieto-Alhambra","doi":"10.3310/LFAJ9337","DOIUrl":"10.3310/LFAJ9337","url":null,"abstract":"<p><strong>Background: </strong>Intra-articular corticosteroid injections are an adjunct to core treatments for osteoarthritis. The National Institute for Health and Care Research Health Technology Assessment programme commissioned this research to address uncertainty around the long-term benefits and potential risks associated with recurrent intra-articular corticosteroid injections.</p><p><strong>Objectives: </strong>Characterise current intra-articular corticosteroid injection practice. Establish longer-term effects and safety of single and recurrent intra-articular corticosteroid injections. Explore views and experiences of patients and clinicians. Assess the priorities/feasibility for future research.</p><p><strong>Methods: </strong>A cohort study of incident osteoarthritis patients (2005-20) was performed using United Kingdom primary care data (Clinical Practice Research Datalink) linked to hospital data (Hospital Episode Statistics). Incidence of first intra-articular corticosteroid injection was stratified by age, calendar year, gender and geographical region. Longer-term outcomes included incident pain medication and joint replacement. Instrumental variables based on practice preference for intra-articular corticosteroid injection were used in primary analyses. Safety was assessed with propensity score matching and a self-controlled cohort, with outcomes (mortality, bleeding, hemarthrosis, wound infection, diabetes, stroke, ischaemic heart disease, myocardial infarction) assessed at 6 months. Semistructured telephone/videocall interviews were conducted (patients = 38, primary care clinicians = 19), with inductive thematic analysis used to investigate views and experiences of intra-articular corticosteroid injections. A three-round modified Delphi study with patients (<i>n</i> = 41), healthcare professionals (<i>n</i> = 25) and academics/researchers (<i>n</i> = 25) was performed to identify future primary research priorities and feasibility.</p><p><strong>Results: </strong>There were 23,899 (10.8%) osteoarthritis patients receiving intra-articular corticosteroid injections (40% received > 1 injection). Incidence of intra-articular corticosteroid injection at 5-year follow-up was lowest for elbow (5.2%) and highest for shoulder (13.6%). Incidences remained stable for all joints between 2005 and 2019 but varied between regions {3.8 [95% confidence interval 3.4 to 4.1] to 1.4 [95% confidence interval 1.3 to 1.5] injections per 100 patient-years}. Intra-articular corticosteroid injection for knee osteoarthritis was associated with lower incident use of several pain medications at 5-year follow-up; recurrent knee intra-articular corticosteroid injections were associated with greater risk reduction. In primary analyses intra-articular corticosteroid injection was associated with a lower 5-year cumulative incidence of knee replacement (number needed to treat 17, 95% confidence interval 12 to 40), but not hip replacement. In certain analyses, inc","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 56","pages":"1-167"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12668259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488616","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}
Filippo Varese, Maria Sudell, Anthony P Morrison, Eleanor Longden, Catrin Tudur Smith
<p><strong>Background: </strong>Cognitive-behavioural therapy is a recommended intervention for the treatment of schizophrenia and related psychoses, but there is considerable uncertainty on whether its effectiveness is moderated by patient characteristics and/or intervention characteristics.</p><p><strong>Objective(s): </strong>To identify treatment effect modifiers of cognitive-behavioural therapy in people with schizophrenia spectrum diagnoses.</p><p><strong>Design: </strong>An individual participant data meta-analysis of randomised controlled trials comparing cognitive-behavioural therapy to treatment as usual or control active psychosocial control interventions.</p><p><strong>Setting: </strong>Community and inpatient settings.</p><p><strong>Participants: </strong>Individuals with schizophrenia spectrum diagnoses.</p><p><strong>Interventions: </strong>Cognitive-behavioural therapy, as defined by the criteria outlined in the National Institute for Health and Care Excellence guideline on treatment and management of schizophrenia in adults.</p><p><strong>Main outcome measures: </strong>Overall symptom change as measured by assessments of overall psychotic symptom severity (e.g. the Positive and Negative Syndrome Scales).</p><p><strong>Data sources: </strong>Corresponding authors of 110 trials identified from the database searches conducted as part of a related aggregate data meta-analysis in February 2018 (later updated in January 2019) were invited to share their trials' individual participant data, and additional trial documentation, when available, pertaining to relevant individual participant data metadata, statistical analyses plans and characteristics of the cognitive-behavioural therapy interventions evaluated in their eligible trials.</p><p><strong>Review methods: </strong>Reports of retrieved and unretrieved trials were assessed using the Cochrane Risk of Bias tool. Data were cleaned and standardised to allow pooling and analysis. We conducted a series of two-stage individual participant data random-effect meta-analyses across four treatment comparisons: cognitive-behavioural therapy versus treatment as usual; cognitive-behavioural therapy versus other psychosocial interventions/active comparisons (active control psychosocial interventions); cognitive-behavioural therapy integrating additional elements from other therapies ('cognitive-behavioural therapy+') versus treatment as usual; and cognitive-behavioural therapy+ versus active control psychosocial interventions. Treatment by covariate interaction analyses were carried out to examine potential treatment effect modifiers, including participants' demographic characteristics (age, gender, ethnicity), clinical characteristics (illness duration, phase of illness, duration of untreated psychosis, initial severity of psychotic symptoms and affective symptoms), and specific intervention characteristics (treatment duration, number of therapy sessions, level of therapists' training/competence
{"title":"Treatment effect modifiers of cognitive behaviour therapy in people with psychosis: an individual participant data meta-analysis of RCTs.","authors":"Filippo Varese, Maria Sudell, Anthony P Morrison, Eleanor Longden, Catrin Tudur Smith","doi":"10.3310/NCFR5074","DOIUrl":"10.3310/NCFR5074","url":null,"abstract":"<p><strong>Background: </strong>Cognitive-behavioural therapy is a recommended intervention for the treatment of schizophrenia and related psychoses, but there is considerable uncertainty on whether its effectiveness is moderated by patient characteristics and/or intervention characteristics.</p><p><strong>Objective(s): </strong>To identify treatment effect modifiers of cognitive-behavioural therapy in people with schizophrenia spectrum diagnoses.</p><p><strong>Design: </strong>An individual participant data meta-analysis of randomised controlled trials comparing cognitive-behavioural therapy to treatment as usual or control active psychosocial control interventions.</p><p><strong>Setting: </strong>Community and inpatient settings.</p><p><strong>Participants: </strong>Individuals with schizophrenia spectrum diagnoses.</p><p><strong>Interventions: </strong>Cognitive-behavioural therapy, as defined by the criteria outlined in the National Institute for Health and Care Excellence guideline on treatment and management of schizophrenia in adults.</p><p><strong>Main outcome measures: </strong>Overall symptom change as measured by assessments of overall psychotic symptom severity (e.g. the Positive and Negative Syndrome Scales).</p><p><strong>Data sources: </strong>Corresponding authors of 110 trials identified from the database searches conducted as part of a related aggregate data meta-analysis in February 2018 (later updated in January 2019) were invited to share their trials' individual participant data, and additional trial documentation, when available, pertaining to relevant individual participant data metadata, statistical analyses plans and characteristics of the cognitive-behavioural therapy interventions evaluated in their eligible trials.</p><p><strong>Review methods: </strong>Reports of retrieved and unretrieved trials were assessed using the Cochrane Risk of Bias tool. Data were cleaned and standardised to allow pooling and analysis. We conducted a series of two-stage individual participant data random-effect meta-analyses across four treatment comparisons: cognitive-behavioural therapy versus treatment as usual; cognitive-behavioural therapy versus other psychosocial interventions/active comparisons (active control psychosocial interventions); cognitive-behavioural therapy integrating additional elements from other therapies ('cognitive-behavioural therapy+') versus treatment as usual; and cognitive-behavioural therapy+ versus active control psychosocial interventions. Treatment by covariate interaction analyses were carried out to examine potential treatment effect modifiers, including participants' demographic characteristics (age, gender, ethnicity), clinical characteristics (illness duration, phase of illness, duration of untreated psychosis, initial severity of psychotic symptoms and affective symptoms), and specific intervention characteristics (treatment duration, number of therapy sessions, level of therapists' training/competence","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 53","pages":"1-115"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12666601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488568","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}
Hemant Pandit, Beth Lineham, Annah Muli, Rachel Kelly, Howard Collier, Ruben Mujica-Mota, Andrew Metcalfe, Hamish Simpson, David Murray, Hemant Sharma, Dennis McGonagle, David R Ellard, Julie Croft, Jamie Stokes, Paul Harwood, Thomas Hamilton, Deborah Stocken
<p><strong>Background: </strong>Patients with symptoms of pain and restricted function related to knee osteoarthritis are typically offered a knee replacement. However, a proportion remain dissatisfied with their outcomes, and the failure risk is disproportionately higher in the young. Knee joint distraction may be an intervention to postpone the time to knee replacement in this patient population.</p><p><strong>Objective and main outcome measure: </strong>The primary objective of the Knee Arthroplasty versus Joint Distraction Study for Osteoarthritis (KARDS) was to evaluate the effectiveness of knee joint distraction compared to knee replacement based on patient-reported pain 12 months post surgery using the Knee Injury and Osteoarthritis Outcomes Score pain score as the primary outcome.</p><p><strong>Design and methods: </strong>KARDS was an open-label, two-arm individually randomised controlled non-inferiority trial with an embedded 12-month internal pilot phase and process evaluation to evaluate recruitment feasibility. A hybrid expertise design was used to account for surgeon expertise and potential lack of individual equipoise. The trial was closed to recruitment early following cessation of elective orthopaedic surgery secondary to COVID-19 pandemic. Descriptive statistics are reported.</p><p><strong>Setting: </strong>United Kingdom National Health Service Trusts.</p><p><strong>Participants: </strong>Adult patients aged < 65 years with symptoms severe enough to warrant knee replacement, in the opinion of the treating clinician.</p><p><strong>Interventions: </strong>Participants were randomised to receive either knee joint distraction (static distraction of 5 mm, using external fixator for 6 weeks) or knee replacement.</p><p><strong>Results: </strong>Twenty-four participants were randomised from a single centre between March 2021 and October 2022 with minimum 3-month safety follow-up post surgery. Eleven participants were randomised to knee joint distraction and 13 to knee replacement. Seventeen patients were male (71%), median age 60 (47-65) years. One patient withdrew due to being medically unfit for surgery and two received a different treatment than which they were randomised (one crossover from each arm). The median Knee Injury and Osteoarthritis Outcomes Score pain score in the knee joint distraction group improved from 38.9 (22-50) at baseline to 55.6 (0-100) at 12 months, corresponding scores in the knee replacement improved from 30.6 (6-36) to 75.0 (50-100). Adverse events were more common with knee joint distraction, pin site infection being the commonest complications (<i>n</i> = 4, 58%). As part of process evaluation, we conducted semistructured qualitative interviews with staff in secondary care and with study participants. Data were analysed using thematic content analysis. One overarching theme emerged: 'An unexpected journey', which encapsulates staff and participants' experiences.</p><p><strong>Conclusion: </strong>Reduced
{"title":"The Knee Arthroplasty versus Joint Distraction Study for Osteoarthritis (KARDS): lessons learnt from an internal pilot trial.","authors":"Hemant Pandit, Beth Lineham, Annah Muli, Rachel Kelly, Howard Collier, Ruben Mujica-Mota, Andrew Metcalfe, Hamish Simpson, David Murray, Hemant Sharma, Dennis McGonagle, David R Ellard, Julie Croft, Jamie Stokes, Paul Harwood, Thomas Hamilton, Deborah Stocken","doi":"10.3310/ANDK1124","DOIUrl":"10.3310/ANDK1124","url":null,"abstract":"<p><strong>Background: </strong>Patients with symptoms of pain and restricted function related to knee osteoarthritis are typically offered a knee replacement. However, a proportion remain dissatisfied with their outcomes, and the failure risk is disproportionately higher in the young. Knee joint distraction may be an intervention to postpone the time to knee replacement in this patient population.</p><p><strong>Objective and main outcome measure: </strong>The primary objective of the Knee Arthroplasty versus Joint Distraction Study for Osteoarthritis (KARDS) was to evaluate the effectiveness of knee joint distraction compared to knee replacement based on patient-reported pain 12 months post surgery using the Knee Injury and Osteoarthritis Outcomes Score pain score as the primary outcome.</p><p><strong>Design and methods: </strong>KARDS was an open-label, two-arm individually randomised controlled non-inferiority trial with an embedded 12-month internal pilot phase and process evaluation to evaluate recruitment feasibility. A hybrid expertise design was used to account for surgeon expertise and potential lack of individual equipoise. The trial was closed to recruitment early following cessation of elective orthopaedic surgery secondary to COVID-19 pandemic. Descriptive statistics are reported.</p><p><strong>Setting: </strong>United Kingdom National Health Service Trusts.</p><p><strong>Participants: </strong>Adult patients aged < 65 years with symptoms severe enough to warrant knee replacement, in the opinion of the treating clinician.</p><p><strong>Interventions: </strong>Participants were randomised to receive either knee joint distraction (static distraction of 5 mm, using external fixator for 6 weeks) or knee replacement.</p><p><strong>Results: </strong>Twenty-four participants were randomised from a single centre between March 2021 and October 2022 with minimum 3-month safety follow-up post surgery. Eleven participants were randomised to knee joint distraction and 13 to knee replacement. Seventeen patients were male (71%), median age 60 (47-65) years. One patient withdrew due to being medically unfit for surgery and two received a different treatment than which they were randomised (one crossover from each arm). The median Knee Injury and Osteoarthritis Outcomes Score pain score in the knee joint distraction group improved from 38.9 (22-50) at baseline to 55.6 (0-100) at 12 months, corresponding scores in the knee replacement improved from 30.6 (6-36) to 75.0 (50-100). Adverse events were more common with knee joint distraction, pin site infection being the commonest complications (<i>n</i> = 4, 58%). As part of process evaluation, we conducted semistructured qualitative interviews with staff in secondary care and with study participants. Data were analysed using thematic content analysis. One overarching theme emerged: 'An unexpected journey', which encapsulates staff and participants' experiences.</p><p><strong>Conclusion: </strong>Reduced ","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 60","pages":"1-29"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523415","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}
Michael R Whitehouse, Nicholas Howells, Lucy Dabner, Russell Thirard, Lucy Culliford, Elsa Marques, Petra Baji, Andrew Judge, Ashley W Blom, Amanda Burston, Catherine Jameson, Chris A Rogers
<p><strong>Background: </strong>Around 10,000 symptomatic knee articular cartilage injuries requiring repair occur annually in the United Kingdom, mostly in people under 35 years of age. Microfracture surgery aims to restore cartilage. Adding microstructural scaffolds made of collagen may further improve outcomes.</p><p><strong>Objectives: </strong>To evaluate the clinical and cost-effectiveness of microstructural scaffold in patients undergoing microfracture for a symptomatic chondral or osteochondral defect of the knee.</p><p><strong>Design: </strong>Multicentre, parallel two-group, superiority randomised controlled trial with blinding of participants, research staff and clinical care teams not involved in the surgery.</p><p><strong>Setting: </strong>National Health Service hospitals offering arthroscopic chondral surgery.</p><p><strong>Participants: </strong>Adults aged 18 years or older with symptomatic chondral or osteochondral defects of the knee on the medial or lateral femoral condyles, trochlea or patella and a chondral or osteochondral lesion measuring no more than 4 cm<sup>2</sup>. Exclusions were: unstable ligamentous injuries or meniscal tears that would not be treated; a knee with defects on the tibial chondral surface, < 50% native meniscal volume or requiring realignment surgery/osteotomy; and a lesion previously treated with microfracture.</p><p><strong>Interventions: </strong>Lesions were debrided, and microfracture was performed on the exposed subchondral bone. Intervention: microfracture of the chondral or osteochondral lesion with insertion of a bilayer collagen matrix microstructural scaffold, fixed with stiches or fibrin glue. Comparator: microfracture alone. Postoperative physiotherapy was standardised. Participants were randomised 1 : 1 between intervention and control.</p><p><strong>Main outcome measures: </strong>Primary outcome was the Knee Injury and Osteoarthritis Outcome Score at 24 months post randomisation. Secondary outcomes included International Knee Documentation Committee knee evaluation score; Tegner-Lysholm activity grading scale; EuroQol-5 Dimensions, five-level version; Work Productivity and Activity Impairment; complications and resource use measured at 3, 6, 12 and 24 months.</p><p><strong>Results: </strong>Twenty-two patients were screened across 8 sites, 20 of whom were eligible on screening. Of the 20 patients considered initially eligible, 2 patients were not interested and 1 opted for chondroplasty; the remaining 17 all consented to participate. Between November 2021 and October 2022, 10 participants were randomised, 5 to microfracture and 5 to microfracture with scaffold. Three patients failed the final in-surgery eligibility check (lesions had healed), one decided not to have surgery and three were still waiting when the study was closed. The median age was 38 years, and four participants were female. Most participants (seven) had damage to the lateral femoral condyle, and six had a medial and/or
{"title":"Microfracture with or without collagen scaffold insertion for adults with chondral or osteochondral defects of the knee: the SISMIC RCT and its challenges during and after the COVID-19 pandemic.","authors":"Michael R Whitehouse, Nicholas Howells, Lucy Dabner, Russell Thirard, Lucy Culliford, Elsa Marques, Petra Baji, Andrew Judge, Ashley W Blom, Amanda Burston, Catherine Jameson, Chris A Rogers","doi":"10.3310/BRTS2415","DOIUrl":"10.3310/BRTS2415","url":null,"abstract":"<p><strong>Background: </strong>Around 10,000 symptomatic knee articular cartilage injuries requiring repair occur annually in the United Kingdom, mostly in people under 35 years of age. Microfracture surgery aims to restore cartilage. Adding microstructural scaffolds made of collagen may further improve outcomes.</p><p><strong>Objectives: </strong>To evaluate the clinical and cost-effectiveness of microstructural scaffold in patients undergoing microfracture for a symptomatic chondral or osteochondral defect of the knee.</p><p><strong>Design: </strong>Multicentre, parallel two-group, superiority randomised controlled trial with blinding of participants, research staff and clinical care teams not involved in the surgery.</p><p><strong>Setting: </strong>National Health Service hospitals offering arthroscopic chondral surgery.</p><p><strong>Participants: </strong>Adults aged 18 years or older with symptomatic chondral or osteochondral defects of the knee on the medial or lateral femoral condyles, trochlea or patella and a chondral or osteochondral lesion measuring no more than 4 cm<sup>2</sup>. Exclusions were: unstable ligamentous injuries or meniscal tears that would not be treated; a knee with defects on the tibial chondral surface, < 50% native meniscal volume or requiring realignment surgery/osteotomy; and a lesion previously treated with microfracture.</p><p><strong>Interventions: </strong>Lesions were debrided, and microfracture was performed on the exposed subchondral bone. Intervention: microfracture of the chondral or osteochondral lesion with insertion of a bilayer collagen matrix microstructural scaffold, fixed with stiches or fibrin glue. Comparator: microfracture alone. Postoperative physiotherapy was standardised. Participants were randomised 1 : 1 between intervention and control.</p><p><strong>Main outcome measures: </strong>Primary outcome was the Knee Injury and Osteoarthritis Outcome Score at 24 months post randomisation. Secondary outcomes included International Knee Documentation Committee knee evaluation score; Tegner-Lysholm activity grading scale; EuroQol-5 Dimensions, five-level version; Work Productivity and Activity Impairment; complications and resource use measured at 3, 6, 12 and 24 months.</p><p><strong>Results: </strong>Twenty-two patients were screened across 8 sites, 20 of whom were eligible on screening. Of the 20 patients considered initially eligible, 2 patients were not interested and 1 opted for chondroplasty; the remaining 17 all consented to participate. Between November 2021 and October 2022, 10 participants were randomised, 5 to microfracture and 5 to microfracture with scaffold. Three patients failed the final in-surgery eligibility check (lesions had healed), one decided not to have surgery and three were still waiting when the study was closed. The median age was 38 years, and four participants were female. Most participants (seven) had damage to the lateral femoral condyle, and six had a medial and/or","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-25"},"PeriodicalIF":4.0,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12666602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145431262","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}
Chikomborero Cynthia Mutepfa, Jana Suklan, Jennifer Bell, Mary Guiney, William Jones, John Simpson, Ronan McMullan
<p><strong>Background: </strong>Invasive candidiasis is a fungal infection of the blood or organs that is associated with high morbidity and mortality in critically ill patients. Current diagnosis is based on blood culture, which typically takes 2 days to confirm the presence of <i>Candida</i>, and longer for differentiating the species and sensitivities to antifungal drugs. Administration of antifungal treatment is time-critical, hence critically ill patients considered 'at-risk' of <i>Candida</i> infection are often started on antifungal treatment pending test results. However, many of these patients may not have empirical treatment stopped when test results become available because of concerns about the sensitivity of blood culture. The Antifungal STewardship Opportunities study is a multisite national diagnostic test accuracy study investigating the use of rapid tests in the intensive care unit that have the potential to influence decision-making.</p><p><strong>Objective(s), study design, settings and participants: </strong>Our aim is to understand patient and physician risk preferences for using the Antifungal STewardship Opportunities testing strategy to discontinue empirical antifungal therapy using semi-structured interviews. An a priori sample size of 30 National Health Service staff and 10 patient interviews was selected to elicit information relating to the aims. Interview schedules were developed, and all interviews were conducted via video or teleconferencing between December 2021 and December 2022 and lasted between 10 and 60 minutes. Interviews were recorded, transcribed and subjected to thematic analysis.</p><p><strong>Findings: </strong>Semi-structured interviews were conducted with 21 National Health Service clinicians and seven patients and legal representatives. National Health Service staff were risk-averse to stopping empirical antifungal therapy, especially if the patient was improving, while patients were risk-neutral. Although there is a clear unmet need for new rapid testing strategy, clinical confidence in its accuracy, clinical utility, cost-effectiveness and usability were strong factors for its consideration for use in decision-making and adoption. Patients did not exhibit strong feelings towards stopping empirical antifungal treatment as they expressed reliance on clinical judgement.</p><p><strong>Limitations: </strong>There was a potential for selection bias as interview participants being from participating sites. The target recruitment numbers of patients and their legal representatives was not achieved due to low retention rates.</p><p><strong>Conclusions: </strong>If found to have high accuracy and cost-effectiveness, the potential of the Antifungal STewardship Opportunities diagnostic strategy to aid decision-making on antifungal prescribing could change intensive care unit clinicians practice, as they are risk-averse to stopping empirical antifungal treatment. However, consideration of the resources needed in
{"title":"Rapid diagnostic tests to inform clinical decision-making for antifungal stewardship in the ICU: a qualitative study with NHS staff, patients, and their legal representatives.","authors":"Chikomborero Cynthia Mutepfa, Jana Suklan, Jennifer Bell, Mary Guiney, William Jones, John Simpson, Ronan McMullan","doi":"10.3310/GJRM3321","DOIUrl":"10.3310/GJRM3321","url":null,"abstract":"<p><strong>Background: </strong>Invasive candidiasis is a fungal infection of the blood or organs that is associated with high morbidity and mortality in critically ill patients. Current diagnosis is based on blood culture, which typically takes 2 days to confirm the presence of <i>Candida</i>, and longer for differentiating the species and sensitivities to antifungal drugs. Administration of antifungal treatment is time-critical, hence critically ill patients considered 'at-risk' of <i>Candida</i> infection are often started on antifungal treatment pending test results. However, many of these patients may not have empirical treatment stopped when test results become available because of concerns about the sensitivity of blood culture. The Antifungal STewardship Opportunities study is a multisite national diagnostic test accuracy study investigating the use of rapid tests in the intensive care unit that have the potential to influence decision-making.</p><p><strong>Objective(s), study design, settings and participants: </strong>Our aim is to understand patient and physician risk preferences for using the Antifungal STewardship Opportunities testing strategy to discontinue empirical antifungal therapy using semi-structured interviews. An a priori sample size of 30 National Health Service staff and 10 patient interviews was selected to elicit information relating to the aims. Interview schedules were developed, and all interviews were conducted via video or teleconferencing between December 2021 and December 2022 and lasted between 10 and 60 minutes. Interviews were recorded, transcribed and subjected to thematic analysis.</p><p><strong>Findings: </strong>Semi-structured interviews were conducted with 21 National Health Service clinicians and seven patients and legal representatives. National Health Service staff were risk-averse to stopping empirical antifungal therapy, especially if the patient was improving, while patients were risk-neutral. Although there is a clear unmet need for new rapid testing strategy, clinical confidence in its accuracy, clinical utility, cost-effectiveness and usability were strong factors for its consideration for use in decision-making and adoption. Patients did not exhibit strong feelings towards stopping empirical antifungal treatment as they expressed reliance on clinical judgement.</p><p><strong>Limitations: </strong>There was a potential for selection bias as interview participants being from participating sites. The target recruitment numbers of patients and their legal representatives was not achieved due to low retention rates.</p><p><strong>Conclusions: </strong>If found to have high accuracy and cost-effectiveness, the potential of the Antifungal STewardship Opportunities diagnostic strategy to aid decision-making on antifungal prescribing could change intensive care unit clinicians practice, as they are risk-averse to stopping empirical antifungal treatment. However, consideration of the resources needed in","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-19"},"PeriodicalIF":4.0,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><strong>Background: </strong>Breast cancer is the most commonly diagnosed cancer in women in England. Breast cancer and chemotherapy treatment can impact upon patients' quality of life and survival. Tumour profiling tests can help to identify whether patients will benefit from chemotherapy.</p><p><strong>Objectives: </strong>To evaluate the effectiveness and cost-effectiveness of four tumour profiling tests (Oncotype DX, Prosigna, EPclin and MammaPrint), compared with current decision-making (no testing), to guide use of adjuvant chemotherapy in people with hormone-receptor positive, human epidermal growth factor receptor 2 negative, early-stage breast cancer with one to three positive lymph nodes.</p><p><strong>Methods and data sources: </strong>A systematic review identified studies via a literature search in April 2023 and from our previous review. The economic analysis included a review of existing models and development of an independent model.</p><p><strong>Results: </strong>Fifty-five articles were included, 42 for prognostic and predictive ability and 13 for impact on chemotherapy decisions. All four tests showed prognostic ability for determining risk of relapse. The RxPONDER randomised controlled trial of Oncotype DX indicated no chemotherapy benefit in post-menopausal lymph node-positive patients with a recurrence score of 0-25, but a statistically significant benefit in pre-menopausal patients with a recurrence score of 0-25. An older randomised controlled trial reanalysis (Southwest Oncology Group-8814) indicated lower relative chemotherapy benefit with lower recurrence score, with statistically significant interactions between recurrence score and chemotherapy benefit in some but not all analyses. There was no clear evidence of prediction of relative chemotherapy benefit for Prosigna, EPclin or MammaPrint. Decision impact studies in lymph node-positive populations in the United Kingdom and Europe were only available for Oncotype DX, and they reported a reduction of 12-75% in chemotherapy recommendations following testing. Based on the list prices of the tests and downstream treatments, the independent model suggests the following.</p><p><strong>Oncotype dx: </strong>This test dominates current decision-making in post-menopausal lymph node-positive women, provided an assumption of predictive benefit holds, but the test is dominated if this assumption does not hold. The test is dominated by current decision-making in pre-menopausal lymph node-positive women.</p><p><strong>Prosigna: </strong>The probabilistic incremental cost-effectiveness ratio for Prosigna versus current decision-making in post-menopausal lymph node-positive women is £39,357 per quality-adjusted life-year gained.</p><p><strong>Epclin: </strong>The probabilistic incremental cost-effectiveness ratio for EPclin versus current decision-making in post-menopausal lymph node-positive women is £4113 per quality-adjusted life-year gained.</p><p><strong>Mammaprint: </strong
{"title":"Tumour profiling tests to guide adjuvant chemotherapy decisions in lymph node-positive early breast cancer: a systematic review and economic evaluation.","authors":"Paul Tappenden, Katy Cooper, Jean Hamilton, Gamze Nalbant, Munira Essat, Annabel Rayner, Ruth Wong, Nicolò Matteo Luca Battisti, Lynda Wyld, Uzma Asghar","doi":"10.3310/KGFD4040","DOIUrl":"10.3310/KGFD4040","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the most commonly diagnosed cancer in women in England. Breast cancer and chemotherapy treatment can impact upon patients' quality of life and survival. Tumour profiling tests can help to identify whether patients will benefit from chemotherapy.</p><p><strong>Objectives: </strong>To evaluate the effectiveness and cost-effectiveness of four tumour profiling tests (Oncotype DX, Prosigna, EPclin and MammaPrint), compared with current decision-making (no testing), to guide use of adjuvant chemotherapy in people with hormone-receptor positive, human epidermal growth factor receptor 2 negative, early-stage breast cancer with one to three positive lymph nodes.</p><p><strong>Methods and data sources: </strong>A systematic review identified studies via a literature search in April 2023 and from our previous review. The economic analysis included a review of existing models and development of an independent model.</p><p><strong>Results: </strong>Fifty-five articles were included, 42 for prognostic and predictive ability and 13 for impact on chemotherapy decisions. All four tests showed prognostic ability for determining risk of relapse. The RxPONDER randomised controlled trial of Oncotype DX indicated no chemotherapy benefit in post-menopausal lymph node-positive patients with a recurrence score of 0-25, but a statistically significant benefit in pre-menopausal patients with a recurrence score of 0-25. An older randomised controlled trial reanalysis (Southwest Oncology Group-8814) indicated lower relative chemotherapy benefit with lower recurrence score, with statistically significant interactions between recurrence score and chemotherapy benefit in some but not all analyses. There was no clear evidence of prediction of relative chemotherapy benefit for Prosigna, EPclin or MammaPrint. Decision impact studies in lymph node-positive populations in the United Kingdom and Europe were only available for Oncotype DX, and they reported a reduction of 12-75% in chemotherapy recommendations following testing. Based on the list prices of the tests and downstream treatments, the independent model suggests the following.</p><p><strong>Oncotype dx: </strong>This test dominates current decision-making in post-menopausal lymph node-positive women, provided an assumption of predictive benefit holds, but the test is dominated if this assumption does not hold. The test is dominated by current decision-making in pre-menopausal lymph node-positive women.</p><p><strong>Prosigna: </strong>The probabilistic incremental cost-effectiveness ratio for Prosigna versus current decision-making in post-menopausal lymph node-positive women is £39,357 per quality-adjusted life-year gained.</p><p><strong>Epclin: </strong>The probabilistic incremental cost-effectiveness ratio for EPclin versus current decision-making in post-menopausal lymph node-positive women is £4113 per quality-adjusted life-year gained.</p><p><strong>Mammaprint: </strong","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 49","pages":"1-158"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274603","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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