Mark Simmonds, Alexis Llewellyn, Ruth Walker, Helen Fulbright, Matthew Walton, Rob Hodgson, Laura Bojke, Lesley Stewart, Sofia Dias, Thomas Rush, John G Lawrenson, Tunde Peto, David Steel
<p><strong>Background: </strong>Diabetic retinopathy is a major cause of sight loss in people with diabetes. The most severe form, proliferative diabetic retinopathy, carries a high risk of vision loss, vitreous haemorrhage, macular oedema and other harms. Panretinal photocoagulation is the primary treatment for proliferative diabetic retinopathy. Anti-vascular endothelial growth factor drugs are used to treat various eye conditions and may be beneficial for people with diabetic retinopathy.</p><p><strong>Objective: </strong>To investigate the efficacy and safety of anti-vascular endothelial growth factor therapy for the treatment of diabetic retinopathy when compared to panretinal photocoagulation.</p><p><strong>Methods: </strong>A systematic review and network meta-analysis of all published randomised controlled trials comparing anti-vascular endothelial growth factor (alone or in combination with panretinal photocoagulation) to panretinal photocoagulation in people with diabetic retinopathy. The database searches were updated in May 2023. Trials where the primary focus was treatment of macular oedema or vitreous haemorrhage were excluded.</p><p><strong>Results: </strong>A total of 14 trials were included: 3 of aflibercept, 5 of bevacizumab and 6 of ranibizumab. Two trials were of patients with non-proliferative diabetic retinopathy; all others were in proliferative diabetic retinopathy. Overall, anti-vascular endothelial growth factor was slightly better than panretinal photocoagulation at preventing vision loss, measured as best corrected visual acuity, at up to 2 years follow-up [mean difference in the logarithm of the minimum angle of resolution -0.089 (or 3.6 Early Treatment Diabetic Retinopathy Study letters), 95% confidence interval -0.180 to -0.019]. There was no clear evidence of any difference between the anti-vascular endothelial growth factors, but the potential for bias complicated the comparison. One trial found no benefit of anti-vascular endothelial growth factor over panretinal photocoagulation after 5 years. Anti-vascular endothelial growth factor was superior to panretinal photocoagulation at preventing macular oedema (relative risk 0.29, 95% confidence interval 0.18 to 0.49) and vitreous haemorrhage (relative risk 0.77, 95% confidence interval 0.61 to 0.99). There was no clear evidence that the effectiveness of anti-vascular endothelial growth factor varied over time.</p><p><strong>Conclusions: </strong>Anti-vascular endothelial growth factor injections reduce vision loss when compared to panretinal photocoagulation, but the benefit is small and unlikely to be clinically meaningful. Anti-vascular endothelial growth factor may have greater benefits for preventing complications such as macular oedema. Observational studies extending follow-up beyond the 1-year duration of most trials are needed to investigate the longer-term effects of repeated anti-vascular endothelial growth factor injections.</p><p><strong>Funding: </strong
{"title":"Anti-VEGF drugs compared with laser photocoagulation for the treatment of diabetic retinopathy: a systematic review and meta-analysis.","authors":"Mark Simmonds, Alexis Llewellyn, Ruth Walker, Helen Fulbright, Matthew Walton, Rob Hodgson, Laura Bojke, Lesley Stewart, Sofia Dias, Thomas Rush, John G Lawrenson, Tunde Peto, David Steel","doi":"10.3310/PCGV5709","DOIUrl":"https://doi.org/10.3310/PCGV5709","url":null,"abstract":"<p><strong>Background: </strong>Diabetic retinopathy is a major cause of sight loss in people with diabetes. The most severe form, proliferative diabetic retinopathy, carries a high risk of vision loss, vitreous haemorrhage, macular oedema and other harms. Panretinal photocoagulation is the primary treatment for proliferative diabetic retinopathy. Anti-vascular endothelial growth factor drugs are used to treat various eye conditions and may be beneficial for people with diabetic retinopathy.</p><p><strong>Objective: </strong>To investigate the efficacy and safety of anti-vascular endothelial growth factor therapy for the treatment of diabetic retinopathy when compared to panretinal photocoagulation.</p><p><strong>Methods: </strong>A systematic review and network meta-analysis of all published randomised controlled trials comparing anti-vascular endothelial growth factor (alone or in combination with panretinal photocoagulation) to panretinal photocoagulation in people with diabetic retinopathy. The database searches were updated in May 2023. Trials where the primary focus was treatment of macular oedema or vitreous haemorrhage were excluded.</p><p><strong>Results: </strong>A total of 14 trials were included: 3 of aflibercept, 5 of bevacizumab and 6 of ranibizumab. Two trials were of patients with non-proliferative diabetic retinopathy; all others were in proliferative diabetic retinopathy. Overall, anti-vascular endothelial growth factor was slightly better than panretinal photocoagulation at preventing vision loss, measured as best corrected visual acuity, at up to 2 years follow-up [mean difference in the logarithm of the minimum angle of resolution -0.089 (or 3.6 Early Treatment Diabetic Retinopathy Study letters), 95% confidence interval -0.180 to -0.019]. There was no clear evidence of any difference between the anti-vascular endothelial growth factors, but the potential for bias complicated the comparison. One trial found no benefit of anti-vascular endothelial growth factor over panretinal photocoagulation after 5 years. Anti-vascular endothelial growth factor was superior to panretinal photocoagulation at preventing macular oedema (relative risk 0.29, 95% confidence interval 0.18 to 0.49) and vitreous haemorrhage (relative risk 0.77, 95% confidence interval 0.61 to 0.99). There was no clear evidence that the effectiveness of anti-vascular endothelial growth factor varied over time.</p><p><strong>Conclusions: </strong>Anti-vascular endothelial growth factor injections reduce vision loss when compared to panretinal photocoagulation, but the benefit is small and unlikely to be clinically meaningful. Anti-vascular endothelial growth factor may have greater benefits for preventing complications such as macular oedema. Observational studies extending follow-up beyond the 1-year duration of most trials are needed to investigate the longer-term effects of repeated anti-vascular endothelial growth factor injections.</p><p><strong>Funding: </strong","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-71"},"PeriodicalIF":3.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824064","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}
Joseph Dias, Puvan Tharmanathan, Catherine Arundel, Charlie Welch, Qi Wu, Paul Leighton, Maria Armaou, Belen Corbacho, Nick Johnson, Sophie James, John Cooke, Christopher Bainbridge, Michael Craigen, David Warwick, Samantha Brady, Lydia Flett, Judy Jones, Catherine Knowlson, Michelle Watson, Ada Keding, Catherine Hewitt, David Torgerson
<p><strong>Background: </strong>Dupuytren's contracture is caused by nodules and cords which pull the fingers towards the palm of the hand. Treatments include limited fasciectomy surgery, collagenase injection and needle fasciotomy. There is limited evidence comparing limited fasciectomy with collagenase injection.</p><p><strong>Objectives: </strong>To compare whether collagenase injection is not inferior to limited fasciectomy when treating Dupuytren's contracture.</p><p><strong>Design: </strong>Pragmatic, two-arm, unblinded, randomised controlled non-inferiority trial with a cost-effectiveness evaluation and nested qualitative and photographic substudies.</p><p><strong>Setting: </strong>Thirty-one National Health Service hospitals in England and Scotland.</p><p><strong>Participants: </strong>Patients with Dupuytren's contracture of ≥ 30 degrees who had not received previous treatment in the same digit.</p><p><strong>Interventions: </strong>Collagenase injection with manipulation 1-7 days later was compared with limited fasciectomy.</p><p><strong>Main outcome measures: </strong>The primary outcome was the Patient Evaluation Measure score, with 1 year after treatment serving as the primary end point. A difference of 6 points in the primary end point was used as the non-inferiority margin. Secondary outcomes included: Unité Rhumatologique des Affections de la Main scale; Michigan Hand Outcomes Questionnaire; recurrence; extension deficit and total active movement; further care/re-intervention; complications; quality-adjusted life-year; resource use; and time to function recovery.</p><p><strong>Randomisation and blinding: </strong>Online central randomisation, stratified by the most affected joint, and with variable block sizes allocates participants 1 : 1 to collagenase or limited fasciectomy. Participants and clinicians were not blind to treatment allocation.</p><p><strong>Results: </strong>Between 31 July 2017 and 28 September 2021, 672 participants were recruited (<i>n</i> = 336 per group), of which 599 participants contributed to the primary outcome analysis (<i>n</i> = 285 limited fasciectomy; <i>n</i> = 314 collagenase). At 1 year (primary end point) there was little evidence to support rejection of the hypothesis that collagenase is inferior to limited fasciectomy. The difference in Patient Evaluation Measure score at 1 year was 5.95 (95% confidence interval 3.12 to 8.77; <i>p</i> = 0.49), increasing to 7.18 (95% confidence interval 4.18 to 10.88) at 2 years. The collagenase group had more complications (<i>n</i> = 267, 0.82 per participant) than the limited fasciectomy group (<i>n</i> = 177, 0.60 per participant), but limited fasciectomy participants had a greater proportion of 'moderate'/'severe' complications (5% vs. 2%). At least 54 participants (15.7%) had contracture recurrence and there was weak evidence suggesting that collagenase participants recurred more often than limited fasciectomy participants (odds ratio 1.39, 95% confidence
{"title":"Collagenase injection versus limited fasciectomy surgery to treat Dupuytren's contracture in adult patients in the UK: DISC, a non-inferiority RCT and economic evaluation.","authors":"Joseph Dias, Puvan Tharmanathan, Catherine Arundel, Charlie Welch, Qi Wu, Paul Leighton, Maria Armaou, Belen Corbacho, Nick Johnson, Sophie James, John Cooke, Christopher Bainbridge, Michael Craigen, David Warwick, Samantha Brady, Lydia Flett, Judy Jones, Catherine Knowlson, Michelle Watson, Ada Keding, Catherine Hewitt, David Torgerson","doi":"10.3310/KGXD8528","DOIUrl":"10.3310/KGXD8528","url":null,"abstract":"<p><strong>Background: </strong>Dupuytren's contracture is caused by nodules and cords which pull the fingers towards the palm of the hand. Treatments include limited fasciectomy surgery, collagenase injection and needle fasciotomy. There is limited evidence comparing limited fasciectomy with collagenase injection.</p><p><strong>Objectives: </strong>To compare whether collagenase injection is not inferior to limited fasciectomy when treating Dupuytren's contracture.</p><p><strong>Design: </strong>Pragmatic, two-arm, unblinded, randomised controlled non-inferiority trial with a cost-effectiveness evaluation and nested qualitative and photographic substudies.</p><p><strong>Setting: </strong>Thirty-one National Health Service hospitals in England and Scotland.</p><p><strong>Participants: </strong>Patients with Dupuytren's contracture of ≥ 30 degrees who had not received previous treatment in the same digit.</p><p><strong>Interventions: </strong>Collagenase injection with manipulation 1-7 days later was compared with limited fasciectomy.</p><p><strong>Main outcome measures: </strong>The primary outcome was the Patient Evaluation Measure score, with 1 year after treatment serving as the primary end point. A difference of 6 points in the primary end point was used as the non-inferiority margin. Secondary outcomes included: Unité Rhumatologique des Affections de la Main scale; Michigan Hand Outcomes Questionnaire; recurrence; extension deficit and total active movement; further care/re-intervention; complications; quality-adjusted life-year; resource use; and time to function recovery.</p><p><strong>Randomisation and blinding: </strong>Online central randomisation, stratified by the most affected joint, and with variable block sizes allocates participants 1 : 1 to collagenase or limited fasciectomy. Participants and clinicians were not blind to treatment allocation.</p><p><strong>Results: </strong>Between 31 July 2017 and 28 September 2021, 672 participants were recruited (<i>n</i> = 336 per group), of which 599 participants contributed to the primary outcome analysis (<i>n</i> = 285 limited fasciectomy; <i>n</i> = 314 collagenase). At 1 year (primary end point) there was little evidence to support rejection of the hypothesis that collagenase is inferior to limited fasciectomy. The difference in Patient Evaluation Measure score at 1 year was 5.95 (95% confidence interval 3.12 to 8.77; <i>p</i> = 0.49), increasing to 7.18 (95% confidence interval 4.18 to 10.88) at 2 years. The collagenase group had more complications (<i>n</i> = 267, 0.82 per participant) than the limited fasciectomy group (<i>n</i> = 177, 0.60 per participant), but limited fasciectomy participants had a greater proportion of 'moderate'/'severe' complications (5% vs. 2%). At least 54 participants (15.7%) had contracture recurrence and there was weak evidence suggesting that collagenase participants recurred more often than limited fasciectomy participants (odds ratio 1.39, 95% confidence","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 78","pages":"1-262"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791513","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}
Asra Asgharzadeh, Mubarak Patel, Martin Connock, Sara Damery, Iman Ghosh, Mary Jordan, Karoline Freeman, Anna Brown, Rachel Court, Sharin Baldwin, Fatai Ogunlayi, Chris Stinton, Ewen Cummins, Lena Al-Khudairy
<p><strong>Background: </strong>Hybrid closed-loop systems are a new class of technology to manage type 1 diabetes mellitus. The system includes a combination of real-time continuous glucose monitoring from a continuous glucose monitoring device and a control algorithm to direct insulin delivery through an insulin pump. Evidence suggests that such technologies have the potential to improve the lives of people with type 1 diabetes mellitus and their families.</p><p><strong>Aim: </strong>The aim of this appraisal was to assess the clinical effectiveness and cost-effectiveness of hybrid closed-loop systems for managing glucose in people who have type 1 diabetes mellitus and are having difficulty managing their condition despite prior use of at least one of the following technologies: continuous subcutaneous insulin infusion, real-time continuous glucose monitoring or flash glucose monitoring (intermittently scanned continuous glucose monitoring).</p><p><strong>Methods: </strong>A systematic review of clinical effectiveness and cost-effectiveness evidence following predefined inclusion criteria informed by the aim of this review. An independent economic assessment using iQVIA CDM to model cost-effectiveness.</p><p><strong>Results: </strong>The clinical evidence identified 12 randomised controlled trials that compared hybrid closed loop with continuous subcutaneous insulin infusion + continuous glucose monitoring. Hybrid closed-loop arm of randomised controlled trials achieved improvement in glycated haemoglobin per cent [hybrid closed loop decreased glycated haemoglobin per cent by 0.28 (95% confidence interval -0.34 to -0.21), increased per cent of time in range (between 3.9 and 10.0 mmol/l) with a MD of 8.6 (95% confidence interval 7.03 to 10.22), and significantly decreased time in range (per cent above 10.0 mmol/l) with a MD of -7.2 (95% confidence interval -8.89 to -5.51), but did not significantly affect per cent of time below range (< 3.9 mmol/l)]. Comparator arms showed improvements, but these were smaller than in the hybrid closed-loop arm. Outcomes were superior in the hybrid closed-loop arm compared with the comparator arm. The cost-effectiveness search identified six studies that were included in the systematic review. Studies reported subjective cost-effectiveness that was influenced by the willingness-to-pay thresholds. Economic evaluation showed that the published model validation papers suggest that an earlier version of the iQVIA CDM tended to overestimate the incidences of the complications of diabetes, this being particularly important for severe visual loss and end-stage renal disease. Overall survival's medium-term modelling appeared good, but there was uncertainty about its longer-term modelling. Costs provided by the National Health Service Supply Chain suggest that hybrid closed loop is around an annual average of £1500 more expensive than continuous subcutaneous insulin infusion + continuous glucose monitoring, this being a
{"title":"Hybrid closed-loop systems for managing blood glucose levels in type 1 diabetes: a systematic review and economic modelling.","authors":"Asra Asgharzadeh, Mubarak Patel, Martin Connock, Sara Damery, Iman Ghosh, Mary Jordan, Karoline Freeman, Anna Brown, Rachel Court, Sharin Baldwin, Fatai Ogunlayi, Chris Stinton, Ewen Cummins, Lena Al-Khudairy","doi":"10.3310/JYPL3536","DOIUrl":"10.3310/JYPL3536","url":null,"abstract":"<p><strong>Background: </strong>Hybrid closed-loop systems are a new class of technology to manage type 1 diabetes mellitus. The system includes a combination of real-time continuous glucose monitoring from a continuous glucose monitoring device and a control algorithm to direct insulin delivery through an insulin pump. Evidence suggests that such technologies have the potential to improve the lives of people with type 1 diabetes mellitus and their families.</p><p><strong>Aim: </strong>The aim of this appraisal was to assess the clinical effectiveness and cost-effectiveness of hybrid closed-loop systems for managing glucose in people who have type 1 diabetes mellitus and are having difficulty managing their condition despite prior use of at least one of the following technologies: continuous subcutaneous insulin infusion, real-time continuous glucose monitoring or flash glucose monitoring (intermittently scanned continuous glucose monitoring).</p><p><strong>Methods: </strong>A systematic review of clinical effectiveness and cost-effectiveness evidence following predefined inclusion criteria informed by the aim of this review. An independent economic assessment using iQVIA CDM to model cost-effectiveness.</p><p><strong>Results: </strong>The clinical evidence identified 12 randomised controlled trials that compared hybrid closed loop with continuous subcutaneous insulin infusion + continuous glucose monitoring. Hybrid closed-loop arm of randomised controlled trials achieved improvement in glycated haemoglobin per cent [hybrid closed loop decreased glycated haemoglobin per cent by 0.28 (95% confidence interval -0.34 to -0.21), increased per cent of time in range (between 3.9 and 10.0 mmol/l) with a MD of 8.6 (95% confidence interval 7.03 to 10.22), and significantly decreased time in range (per cent above 10.0 mmol/l) with a MD of -7.2 (95% confidence interval -8.89 to -5.51), but did not significantly affect per cent of time below range (< 3.9 mmol/l)]. Comparator arms showed improvements, but these were smaller than in the hybrid closed-loop arm. Outcomes were superior in the hybrid closed-loop arm compared with the comparator arm. The cost-effectiveness search identified six studies that were included in the systematic review. Studies reported subjective cost-effectiveness that was influenced by the willingness-to-pay thresholds. Economic evaluation showed that the published model validation papers suggest that an earlier version of the iQVIA CDM tended to overestimate the incidences of the complications of diabetes, this being particularly important for severe visual loss and end-stage renal disease. Overall survival's medium-term modelling appeared good, but there was uncertainty about its longer-term modelling. Costs provided by the National Health Service Supply Chain suggest that hybrid closed loop is around an annual average of £1500 more expensive than continuous subcutaneous insulin infusion + continuous glucose monitoring, this being a ","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 80","pages":"1-190"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824073","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}
Borislava Mihaylova, Runguo Wu, Junwen Zhou, Claire Williams, Iryna Schlackow, Jonathan Emberson, Christina Reith, Anthony Keech, John Robson, Richard Parnell, Jane Armitage, Alastair Gray, John Simes, Colin Baigent
<p><strong>Background: </strong>Cardiovascular disease has declined but remains a major disease burden across developed countries.</p><p><strong>Objective: </strong>To assess the effectiveness and cost-effectiveness of statin therapy across United Kingdom population categories.</p><p><strong>Design: </strong>The cardiovascular disease microsimulation model, developed using Cholesterol Treatment Trialists' Collaboration data and the United Kingdom Biobank cohort, projected cardiovascular events, mortality, quality of life and healthcare costs using participant characteristics.</p><p><strong>Setting: </strong>United Kingdom primary health care.</p><p><strong>Participants: </strong>A total of 117,896 participants in 16 statin trials in the Cholesterol Treatment Trialists' Collaboration; 501,854 United Kingdom Biobank participants by previous cardiovascular disease status, sex, age (40-49, 50-59 and 60-70 years), 10-year cardiovascular disease risk [QRISK<sup>®</sup>3 (%): < 5, 5-10, 10-15, 15-20 and ≥ 20] and low-density lipoprotein cholesterol level (< 3.4, 3.4-4.1 and ≥ 4.1 mmol/l); 20,122 United Kingdom Biobank and Whitehall II participants aged ≥ 70 years by previous cardiovascular disease status, sex and low-density lipoprotein cholesterol (< 3.4, 3.4-4.1 and ≥ 4.1 mmol/l).</p><p><strong>Interventions: </strong>Lifetime standard (35-45% low-density lipoprotein cholesterol reduction) or higher-intensity (≥ 45% reduction) statin.</p><p><strong>Main outcome measures: </strong>Quality-adjusted life-years and incremental cost per quality-adjusted life-year gained from the United Kingdom healthcare perspective.</p><p><strong>Data sources: </strong>Cholesterol Treatment Trialists' Collaboration and United Kingdom Biobank data informed risk equations. United Kingdom primary and hospital care data informed healthcare costs (2020-1 Great British pounds); £1.10 standard or £1.68 higher-intensity generic statin therapy per 28 tablets; and Health Survey for England data informed health-related quality of life. Meta-analyses of trials and cohort studies informed the effects of statin therapies on cardiovascular events, incident diabetes, myopathy and rhabdomyolysis.</p><p><strong>Results: </strong>Across categories of participants 40-70 years old, lifetime use of standard statin therapy resulted in undiscounted 0.20-1.09 quality-adjusted life-years gained per person, and higher-intensity statin therapy added a further 0.03-0.20 quality-adjusted life-years per person. Among participants aged ≥ 70 years, lifetime standard statin was estimated to increase quality-adjusted life-years by 0.24-0.70 and higher-intensity statin by a further 0.04-0.13 quality-adjusted life-years per person. Benefits were larger among participants at higher cardiovascular disease risk or with higher low-density lipoprotein cholesterol. Standard statin therapy was cost-effective across all categories of people 40-70 years old, with incremental costs per quality-adjusted life-year gaine
{"title":"Assessing long-term effectiveness and cost-effectiveness of statin therapy in the UK: a modelling study using individual participant data sets.","authors":"Borislava Mihaylova, Runguo Wu, Junwen Zhou, Claire Williams, Iryna Schlackow, Jonathan Emberson, Christina Reith, Anthony Keech, John Robson, Richard Parnell, Jane Armitage, Alastair Gray, John Simes, Colin Baigent","doi":"10.3310/KDAP7034","DOIUrl":"10.3310/KDAP7034","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease has declined but remains a major disease burden across developed countries.</p><p><strong>Objective: </strong>To assess the effectiveness and cost-effectiveness of statin therapy across United Kingdom population categories.</p><p><strong>Design: </strong>The cardiovascular disease microsimulation model, developed using Cholesterol Treatment Trialists' Collaboration data and the United Kingdom Biobank cohort, projected cardiovascular events, mortality, quality of life and healthcare costs using participant characteristics.</p><p><strong>Setting: </strong>United Kingdom primary health care.</p><p><strong>Participants: </strong>A total of 117,896 participants in 16 statin trials in the Cholesterol Treatment Trialists' Collaboration; 501,854 United Kingdom Biobank participants by previous cardiovascular disease status, sex, age (40-49, 50-59 and 60-70 years), 10-year cardiovascular disease risk [QRISK<sup>®</sup>3 (%): < 5, 5-10, 10-15, 15-20 and ≥ 20] and low-density lipoprotein cholesterol level (< 3.4, 3.4-4.1 and ≥ 4.1 mmol/l); 20,122 United Kingdom Biobank and Whitehall II participants aged ≥ 70 years by previous cardiovascular disease status, sex and low-density lipoprotein cholesterol (< 3.4, 3.4-4.1 and ≥ 4.1 mmol/l).</p><p><strong>Interventions: </strong>Lifetime standard (35-45% low-density lipoprotein cholesterol reduction) or higher-intensity (≥ 45% reduction) statin.</p><p><strong>Main outcome measures: </strong>Quality-adjusted life-years and incremental cost per quality-adjusted life-year gained from the United Kingdom healthcare perspective.</p><p><strong>Data sources: </strong>Cholesterol Treatment Trialists' Collaboration and United Kingdom Biobank data informed risk equations. United Kingdom primary and hospital care data informed healthcare costs (2020-1 Great British pounds); £1.10 standard or £1.68 higher-intensity generic statin therapy per 28 tablets; and Health Survey for England data informed health-related quality of life. Meta-analyses of trials and cohort studies informed the effects of statin therapies on cardiovascular events, incident diabetes, myopathy and rhabdomyolysis.</p><p><strong>Results: </strong>Across categories of participants 40-70 years old, lifetime use of standard statin therapy resulted in undiscounted 0.20-1.09 quality-adjusted life-years gained per person, and higher-intensity statin therapy added a further 0.03-0.20 quality-adjusted life-years per person. Among participants aged ≥ 70 years, lifetime standard statin was estimated to increase quality-adjusted life-years by 0.24-0.70 and higher-intensity statin by a further 0.04-0.13 quality-adjusted life-years per person. Benefits were larger among participants at higher cardiovascular disease risk or with higher low-density lipoprotein cholesterol. Standard statin therapy was cost-effective across all categories of people 40-70 years old, with incremental costs per quality-adjusted life-year gaine","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 79","pages":"1-134"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791515","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}
Mairead Black, Cassandra Yuill, Mairi Harkness, Sayem Ahmed, Linda Williams, Kathleen A Boyd, Maggie Reid, Amar Bhide, Neelam Heera, Jane Huddleston, Neena Modi, John Norrie, Dharmintra Pasupathy, Julia Sanders, Gordon C S Smith, Rosemary Townsend, Helen Cheyne, Christine McCourt, Sarah Stock
<p><strong>Background: </strong>Around one in three pregnant women undergoes induction of labour in the United Kingdom, usually preceded by in-hospital cervical ripening to soften and open the cervix.</p><p><strong>Objectives: </strong>This study set out to determine whether cervical ripening at home is within an acceptable safety margin of cervical ripening in hospital, is effective, acceptable and cost-effective from both National Health Service and service user perspectives.</p><p><strong>Design: </strong>The CHOICE study comprised a prospective multicentre observational cohort study using routinely collected data (CHOICE cohort), a process evaluation comprising a survey and nested case studies (qCHOICE) and a cost-effectiveness analysis. The CHOICE cohort set out to compare outcomes of cervical ripening using dinoprostone (a prostaglandin) at home with in-hospital cervical ripening from 39 weeks of gestation. Electronic maternity record data were collected from 26 maternity units. Following pilot analysis, the primary comparison was changed to ensure feasibility and to reflect current practice, comparing home cervical ripening using a balloon catheter with in-hospital cervical ripening using any prostaglandin from 37 weeks of gestation. Analysis involved multiple logistic regression for the primary outcome and descriptive statistics for all other outcomes. The qCHOICE study reported descriptive statistics of quantitative survey data and thematic analysis of focus group and interview data. The economic analysis involved a decision-analytic model from a National Health Service and Personal Social Services perspective, populated with CHOICE cohort and published data. Secondary analysis explored the patient perspective utilising cost estimates from qCHOICE data.</p><p><strong>Setting: </strong>Twenty-six United Kingdom maternity units.</p><p><strong>Participants: </strong>Women with singleton pregnancies at or beyond 37 weeks of gestation having induction with details of cervical ripening method and location recorded.</p><p><strong>Main outcome measures: </strong>Neonatal unit admission within 48 hours of birth for 48 hours or more.</p><p><strong>Qchoice: </strong>Maternal and staff experience of cervical ripening.</p><p><strong>Economic analysis: </strong>Incremental cost per neonatal unit admission within 48 hours of birth avoided.</p><p><strong>Data sources: </strong>Electronic maternity records from 26 maternity units; survey and interviews with service users/maternity staff; focus groups with maternity staff; published literature on economic aspects.</p><p><strong>Results: </strong>CHOICE cohort: A total of 515 women underwent balloon cervical ripening at home and 4332 underwent in-hospital cervical ripening using prostaglandin in hospitals that did not offer home cervical ripening. Neonatal unit admission within 48 hours of birth for 48 hours or more following home cervical ripening with balloon was not increased compared with in-hospital c
{"title":"Cervical ripening at home or in hospital during induction of labour: the CHOICE prospective cohort study, process evaluation and economic analysis.","authors":"Mairead Black, Cassandra Yuill, Mairi Harkness, Sayem Ahmed, Linda Williams, Kathleen A Boyd, Maggie Reid, Amar Bhide, Neelam Heera, Jane Huddleston, Neena Modi, John Norrie, Dharmintra Pasupathy, Julia Sanders, Gordon C S Smith, Rosemary Townsend, Helen Cheyne, Christine McCourt, Sarah Stock","doi":"10.3310/LPYT7894","DOIUrl":"10.3310/LPYT7894","url":null,"abstract":"<p><strong>Background: </strong>Around one in three pregnant women undergoes induction of labour in the United Kingdom, usually preceded by in-hospital cervical ripening to soften and open the cervix.</p><p><strong>Objectives: </strong>This study set out to determine whether cervical ripening at home is within an acceptable safety margin of cervical ripening in hospital, is effective, acceptable and cost-effective from both National Health Service and service user perspectives.</p><p><strong>Design: </strong>The CHOICE study comprised a prospective multicentre observational cohort study using routinely collected data (CHOICE cohort), a process evaluation comprising a survey and nested case studies (qCHOICE) and a cost-effectiveness analysis. The CHOICE cohort set out to compare outcomes of cervical ripening using dinoprostone (a prostaglandin) at home with in-hospital cervical ripening from 39 weeks of gestation. Electronic maternity record data were collected from 26 maternity units. Following pilot analysis, the primary comparison was changed to ensure feasibility and to reflect current practice, comparing home cervical ripening using a balloon catheter with in-hospital cervical ripening using any prostaglandin from 37 weeks of gestation. Analysis involved multiple logistic regression for the primary outcome and descriptive statistics for all other outcomes. The qCHOICE study reported descriptive statistics of quantitative survey data and thematic analysis of focus group and interview data. The economic analysis involved a decision-analytic model from a National Health Service and Personal Social Services perspective, populated with CHOICE cohort and published data. Secondary analysis explored the patient perspective utilising cost estimates from qCHOICE data.</p><p><strong>Setting: </strong>Twenty-six United Kingdom maternity units.</p><p><strong>Participants: </strong>Women with singleton pregnancies at or beyond 37 weeks of gestation having induction with details of cervical ripening method and location recorded.</p><p><strong>Main outcome measures: </strong>Neonatal unit admission within 48 hours of birth for 48 hours or more.</p><p><strong>Qchoice: </strong>Maternal and staff experience of cervical ripening.</p><p><strong>Economic analysis: </strong>Incremental cost per neonatal unit admission within 48 hours of birth avoided.</p><p><strong>Data sources: </strong>Electronic maternity records from 26 maternity units; survey and interviews with service users/maternity staff; focus groups with maternity staff; published literature on economic aspects.</p><p><strong>Results: </strong>CHOICE cohort: A total of 515 women underwent balloon cervical ripening at home and 4332 underwent in-hospital cervical ripening using prostaglandin in hospitals that did not offer home cervical ripening. Neonatal unit admission within 48 hours of birth for 48 hours or more following home cervical ripening with balloon was not increased compared with in-hospital c","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 81","pages":"1-142"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871914","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}
Nicola Curry, Ross Davenport, Helen Thomas, Erin Fox, Joanne Lucas, Amy Evans, Efthalia Massou, Rupa Sharma, Shaminie Shanmugaranjan, Claire Rourke, Alice Newton, Alison Deary, Nikki Dallas, Chloe Fitzpatrick-Creamer, Jeanette M Podbielski, Charles E Wade, Antoinette Edwards, Jonathan Benger, Stephen Morris, Bryan A Cotton, James Piercy, Laura Green, Karim Brohi, Simon Stanworth
<p><strong>Background: </strong>Traumatic haemorrhage is common after severe injury, leading to disability and death. Cryoprecipitate, a source of fibrinogen, may improve outcomes for patients with traumatic haemorrhage.</p><p><strong>Objective: </strong>To investigate the effects of early fibrinogen supplementation in the form of 3 pools (15 units, approximately 6 g of fibrinogen) of cryoprecipitate on 28-day mortality.</p><p><strong>Design: </strong>A randomised, parallel-group, unblinded, multicentre, international trial and economic evaluation. Patients were randomised to either the intervention (early cryoprecipitate) or the comparator (standard major haemorrhage protocol) arm via opaque, sealed envelopes in the emergency department or the transfusion laboratory/blood bank. All analyses were performed on an intention-to-treat basis. A cost-effectiveness analysis was undertaken.</p><p><strong>Setting: </strong>Twenty-five major trauma centres in the UK and one level 1 trauma centre in the USA.</p><p><strong>Participants: </strong>Adults who had traumatic haemorrhage following severe injury requiring activation of the major haemorrhage protocol and had received a blood transfusion.</p><p><strong>Intervention: </strong>Early cryoprecipitate - 3 pools (equivalent to 15 single units of cryoprecipitate or 6 g of fibrinogen supplementation), infused as rapidly as possible, within 90 minutes of arrival at hospital in addition to standard major haemorrhage protocol or standard major haemorrhage protocol only.</p><p><strong>Main outcome measures: </strong>The primary outcome was all-cause mortality at 28 days. The secondary outcomes were all-cause mortality at 6 hours, 24 hours, 6 months and 12 months from admission; death from bleeding at 6 hours and 24 hours; transfusion requirements at 24 hours from admission; destination of participant at discharge; quality-of-life measurements (EuroQol-5 Dimensions, five-level version and Glasgow Outcome Scale) at discharge/day 28 and 6 months after injury; and hospital resource use up to discharge or day 28 (including ventilator-days, hours spent in critical care and inpatient stays).</p><p><strong>Results: </strong>Eight hundred and five patients were randomised to receive the standard major haemorrhage protocol (control arm). Seven hundred and ninety-nine patients were randomised to receive an additional three pools of cryoprecipitate in addition to standard care (intervention arm). Baseline characteristics appeared well matched. Patients had a median age of 39 (interquartile range 26-55) years, and the majority (79%) were male. All-cause 28-day mortality (<i>n</i> = 1531 patients; intention to treat) was 25.3% in the intervention arm compared with 26.1% in the control arm (odds ratio 0.96; <i>p</i> = 0.74).</p><p><strong>Limitations: </strong>There was variability in the timing of cryoprecipitate administration, with overlap between the treatment arms, limiting the degree of intervention separation.</p><p><st
{"title":"Early high-dose cryoprecipitate to reduce mortality in adult patients with traumatic haemorrhage: the CRYOSTAT-2 RCT with cost-effectiveness analysis.","authors":"Nicola Curry, Ross Davenport, Helen Thomas, Erin Fox, Joanne Lucas, Amy Evans, Efthalia Massou, Rupa Sharma, Shaminie Shanmugaranjan, Claire Rourke, Alice Newton, Alison Deary, Nikki Dallas, Chloe Fitzpatrick-Creamer, Jeanette M Podbielski, Charles E Wade, Antoinette Edwards, Jonathan Benger, Stephen Morris, Bryan A Cotton, James Piercy, Laura Green, Karim Brohi, Simon Stanworth","doi":"10.3310/JYTR6938","DOIUrl":"10.3310/JYTR6938","url":null,"abstract":"<p><strong>Background: </strong>Traumatic haemorrhage is common after severe injury, leading to disability and death. Cryoprecipitate, a source of fibrinogen, may improve outcomes for patients with traumatic haemorrhage.</p><p><strong>Objective: </strong>To investigate the effects of early fibrinogen supplementation in the form of 3 pools (15 units, approximately 6 g of fibrinogen) of cryoprecipitate on 28-day mortality.</p><p><strong>Design: </strong>A randomised, parallel-group, unblinded, multicentre, international trial and economic evaluation. Patients were randomised to either the intervention (early cryoprecipitate) or the comparator (standard major haemorrhage protocol) arm via opaque, sealed envelopes in the emergency department or the transfusion laboratory/blood bank. All analyses were performed on an intention-to-treat basis. A cost-effectiveness analysis was undertaken.</p><p><strong>Setting: </strong>Twenty-five major trauma centres in the UK and one level 1 trauma centre in the USA.</p><p><strong>Participants: </strong>Adults who had traumatic haemorrhage following severe injury requiring activation of the major haemorrhage protocol and had received a blood transfusion.</p><p><strong>Intervention: </strong>Early cryoprecipitate - 3 pools (equivalent to 15 single units of cryoprecipitate or 6 g of fibrinogen supplementation), infused as rapidly as possible, within 90 minutes of arrival at hospital in addition to standard major haemorrhage protocol or standard major haemorrhage protocol only.</p><p><strong>Main outcome measures: </strong>The primary outcome was all-cause mortality at 28 days. The secondary outcomes were all-cause mortality at 6 hours, 24 hours, 6 months and 12 months from admission; death from bleeding at 6 hours and 24 hours; transfusion requirements at 24 hours from admission; destination of participant at discharge; quality-of-life measurements (EuroQol-5 Dimensions, five-level version and Glasgow Outcome Scale) at discharge/day 28 and 6 months after injury; and hospital resource use up to discharge or day 28 (including ventilator-days, hours spent in critical care and inpatient stays).</p><p><strong>Results: </strong>Eight hundred and five patients were randomised to receive the standard major haemorrhage protocol (control arm). Seven hundred and ninety-nine patients were randomised to receive an additional three pools of cryoprecipitate in addition to standard care (intervention arm). Baseline characteristics appeared well matched. Patients had a median age of 39 (interquartile range 26-55) years, and the majority (79%) were male. All-cause 28-day mortality (<i>n</i> = 1531 patients; intention to treat) was 25.3% in the intervention arm compared with 26.1% in the control arm (odds ratio 0.96; <i>p</i> = 0.74).</p><p><strong>Limitations: </strong>There was variability in the timing of cryoprecipitate administration, with overlap between the treatment arms, limiting the degree of intervention separation.</p><p><st","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 76","pages":"1-69"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638748","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}
Eve Tomlinson, Mary Ward, Chris Cooper, Rachel James, Christina Stokes, Samina Begum, Jessica Watson, Alastair D Hay, Hayley E Jones, Howard Thom, Penny Whiting
<p><strong>Background: </strong>Urinary tract infections are diagnosed by general practitioners based on symptoms, dipstick tests in some and laboratory urine culture. Patients may be given inappropriate antibiotics. Point-of-care tests can diagnose urinary tract infection in near-patient settings quicker than standard culture. Some can identify the causative pathogen or antimicrobial sensitivity.</p><p><strong>Objective: </strong>To assess whether point-of-care tests for people with suspected urinary tract infection have the potential to be clinically effective and cost-effective to the NHS.</p><p><strong>Design: </strong>Systematic review and conceptual economic model.</p><p><strong>Results: </strong>Two randomised controlled trials evaluated Flexicult Human (one against standard care; one against ID Flexicult). One trial found no evidence of a difference between groups in concordant antibiotic use (odds ratio 0.84, 95% confidence interval 0.58 to 1.20), and the other found no difference in appropriate antibiotic prescribing (odds ratio 1.44, 95% confidence interval 1.03 to 1.99). Compared with standard care, Flexicult was associated with reduced antibiotic prescribing at initial consultation (odds ratio 0.56, 95% confidence interval 0.35 to 0.88). No difference was found for other outcomes. Sixteen studies reported test accuracy data. Most were rated as being at unclear or high risk of bias. We identified data on three rapid tests (results < 40 minutes). Lodestar DX (<i>n</i> = 1) had good sensitivity (86%, 95% confidence interval 74% to 99%) and specificity (88%, 95% confidence interval 83% to 94%) for detecting <i>Escherichia coli.</i> Uriscreen (<i>n</i> = 4) had modest summary sensitivity (74%, 95% confidence interval 59% to 84%) and specificity (64%, 95% confidence interval 41% to 82%). UTRiPLEX (<i>n</i> = 1) had poor sensitivity (21%) and good specificity (94%). Twelve studies evaluated culture-based tests (results 24 hours). Laboratory-based studies found Dipstreak (<i>n</i> = 2) and Uricult (<i>n</i> = 1) to be highly accurate, but there were limitations with these studies. Uricult Trio (<i>n</i> = 3) had more modest summary sensitivity (73%, 95% confidence interval 63% to 82%) and specificity (70%, 95% confidence interval 52% to 84%). Summary sensitivity for Flexicult Human (<i>n</i> = 4) and ID Flexicult (<i>n</i> = 2) was 79% (95% confidence interval 72% to 85%) and 89% (95% confidence interval 84% to 93%). Summary specificity was 67% (95% confidence interval 30% to 90%) and 70% (95% confidence interval 52% to 84%). Caution is needed in interpreting findings because of heterogeneity and limited data. Five studies evaluated technical performance (Flexicult Human, <i>n</i> = 3; Uricult Trio, <i>n</i> = 2). Limited data suggested that they are easier to use and interpret than standard culture. A conceptual economic model estimated the cost-effectiveness of point-of-care tests for urinary tract infection diagnosis, pathogen identificat
背景：尿路感染由全科医生根据症状、部分患者的试纸试验和实验室尿培养来诊断。患者可能被给予不适当的抗生素。即时检测可以比标准培养更快地在近病人环境中诊断尿路感染。有些可以识别致病病原体或抗菌素敏感性。目的：评估对疑似尿路感染患者的即时检测是否具有临床有效性和成本效益的潜力。设计：系统回顾和概念经济模型。结果：两项随机对照试验评估了Flexicult Human(一项与标准治疗对照；一个反对ID Flexicult)。一项试验未发现两组在一致抗生素使用方面存在差异（优势比0.84,95%可信区间0.58至1.20），另一项试验未发现适当抗生素处方方面存在差异（优势比1.44,95%可信区间1.03至1.99）。与标准护理相比，Flexicult与初次会诊时抗生素处方减少相关（优势比0.56,95%可信区间0.35 ~ 0.88）。其他结果没有发现差异。16项研究报告了测试准确性数据。大多数被评为不明确或高偏倚风险。我们发现三种快速检测方法（结果n = 1）对检测大肠杆菌具有良好的灵敏度（86%，95%置信区间74% ~ 99%）和特异性（88%，95%置信区间83% ~ 94%）。Uriscreen （n = 4）具有中等的总敏感性（74%，95%可信区间59%至84%）和特异性（64%，95%可信区间41%至82%）。UTRiPLEX （n = 1）敏感性较差（21%），特异性较好（94%）。12项研究评估了基于培养的测试（结果24小时）。基于实验室的研究发现Dipstreak （n = 2）和Uricult （n = 1）非常准确，但这些研究存在局限性。Uricult Trio （n = 3）的总体敏感性（73%，95%可信区间为63% ~ 82%）和特异性（70%，95%可信区间为52% ~ 84%）较中等。Flexicult Human （n = 4）和ID Flexicult （n = 2）的总敏感性分别为79%（95%可信区间72% ~ 85%）和89%（95%可信区间84% ~ 93%）。总结特异性为67%（95%置信区间为30% ~ 90%）和70%（95%置信区间为52% ~ 84%）。由于异质性和有限的数据，在解释研究结果时需要谨慎。5项研究评估了技术性能(Flexicult Human, n = 3；Uricult Trio, n = 2)。有限的数据表明，它们比标准文化更容易使用和解释。一个概念经济模型估计了尿路感染诊断、病原体鉴定和抗菌药物敏感性测试的护理点测试的成本效益。试验的敏感性和特异性由临床疗效评价告知。对审查确定的研究进行了筛选，以获得有关治疗效果、成本和效用数据的证据；只有两项研究提供了相关证据。一项务实的研究确定了八项成本效益研究，提供了进一步的证据。采用决策树比较混合人群（Lodestar DX vs Flexicult Human）和无并发症尿路感染女性（Lodestar DX vs Flexicult Human vs ID Flexicult）的护理点检测。可用的输入数据太有限，结果没有意义。结论和未来的工作：需要更多的研究来确定尿路感染的即时检测是否对NHS具有临床有效性和成本效益的潜力。Astrego PA-100系统和Lodestar DX等快速测试看起来很有希望，但数据非常有限。研究注册：本研究注册号为PROSPERO CRD42022383889。资助：该奖项由美国国家卫生与保健研究所（NIHR）证据综合计划（NIHR奖励编号：NIHR135710）资助，全文发表在《卫生技术评估》上；第28卷，第77号。有关进一步的奖励信息，请参阅美国国立卫生研究院资助和奖励网站。
{"title":"Point-of-care tests for urinary tract infections to reduce antimicrobial resistance: a systematic review and conceptual economic model.","authors":"Eve Tomlinson, Mary Ward, Chris Cooper, Rachel James, Christina Stokes, Samina Begum, Jessica Watson, Alastair D Hay, Hayley E Jones, Howard Thom, Penny Whiting","doi":"10.3310/PTMV8524","DOIUrl":"10.3310/PTMV8524","url":null,"abstract":"<p><strong>Background: </strong>Urinary tract infections are diagnosed by general practitioners based on symptoms, dipstick tests in some and laboratory urine culture. Patients may be given inappropriate antibiotics. Point-of-care tests can diagnose urinary tract infection in near-patient settings quicker than standard culture. Some can identify the causative pathogen or antimicrobial sensitivity.</p><p><strong>Objective: </strong>To assess whether point-of-care tests for people with suspected urinary tract infection have the potential to be clinically effective and cost-effective to the NHS.</p><p><strong>Design: </strong>Systematic review and conceptual economic model.</p><p><strong>Results: </strong>Two randomised controlled trials evaluated Flexicult Human (one against standard care; one against ID Flexicult). One trial found no evidence of a difference between groups in concordant antibiotic use (odds ratio 0.84, 95% confidence interval 0.58 to 1.20), and the other found no difference in appropriate antibiotic prescribing (odds ratio 1.44, 95% confidence interval 1.03 to 1.99). Compared with standard care, Flexicult was associated with reduced antibiotic prescribing at initial consultation (odds ratio 0.56, 95% confidence interval 0.35 to 0.88). No difference was found for other outcomes. Sixteen studies reported test accuracy data. Most were rated as being at unclear or high risk of bias. We identified data on three rapid tests (results < 40 minutes). Lodestar DX (<i>n</i> = 1) had good sensitivity (86%, 95% confidence interval 74% to 99%) and specificity (88%, 95% confidence interval 83% to 94%) for detecting <i>Escherichia coli.</i> Uriscreen (<i>n</i> = 4) had modest summary sensitivity (74%, 95% confidence interval 59% to 84%) and specificity (64%, 95% confidence interval 41% to 82%). UTRiPLEX (<i>n</i> = 1) had poor sensitivity (21%) and good specificity (94%). Twelve studies evaluated culture-based tests (results 24 hours). Laboratory-based studies found Dipstreak (<i>n</i> = 2) and Uricult (<i>n</i> = 1) to be highly accurate, but there were limitations with these studies. Uricult Trio (<i>n</i> = 3) had more modest summary sensitivity (73%, 95% confidence interval 63% to 82%) and specificity (70%, 95% confidence interval 52% to 84%). Summary sensitivity for Flexicult Human (<i>n</i> = 4) and ID Flexicult (<i>n</i> = 2) was 79% (95% confidence interval 72% to 85%) and 89% (95% confidence interval 84% to 93%). Summary specificity was 67% (95% confidence interval 30% to 90%) and 70% (95% confidence interval 52% to 84%). Caution is needed in interpreting findings because of heterogeneity and limited data. Five studies evaluated technical performance (Flexicult Human, <i>n</i> = 3; Uricult Trio, <i>n</i> = 2). Limited data suggested that they are easier to use and interpret than standard culture. A conceptual economic model estimated the cost-effectiveness of point-of-care tests for urinary tract infection diagnosis, pathogen identificat","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 77","pages":"1-109"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katie E Webster, Tom Parkhouse, Sarah Dawson, Hayley E Jones, Emily L Brown, Alastair D Hay, Penny Whiting, Christie Cabral, Deborah M Caldwell, Julian Pt Higgins
<p><strong>Background: </strong>Acute respiratory infections are a common reason for consultation with primary and emergency healthcare services. Identifying individuals with a bacterial infection is crucial to ensure appropriate treatment. However, it is also important to avoid overprescription of antibiotics, to prevent unnecessary side effects and antimicrobial resistance. We conducted a systematic review to summarise evidence on the diagnostic accuracy of symptoms, signs and point-of-care tests to diagnose bacterial respiratory tract infection in adults, and to diagnose two common respiratory viruses, influenza and respiratory syncytial virus.</p><p><strong>Methods: </strong>The primary approach was an overview of existing systematic reviews. We conducted literature searches (22 May 2023) to identify systematic reviews of the diagnostic accuracy of point-of-care tests. Where multiple reviews were identified, we selected the most recent and comprehensive review, with the greatest overlap in scope with our review question. Methodological quality was assessed using the Risk of Bias in Systematic Reviews tool. Summary estimates of diagnostic accuracy (sensitivity, specificity or area under the curve) were extracted. Where no systematic review was identified, we searched for primary studies. We extracted sufficient data to construct a 2 × 2 table of diagnostic accuracy, to calculate sensitivity and specificity. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies version 2 tool. Where possible, meta-analyses were conducted. We used GRADE to assess the certainty of the evidence from existing reviews and new analyses.</p><p><strong>Results: </strong>We identified 23 reviews which addressed our review question; 6 were selected as the most comprehensive and similar in scope to our review protocol. These systematic reviews considered the following tests for bacterial respiratory infection: individual symptoms and signs; combinations of symptoms and signs (in clinical prediction models); clinical prediction models incorporating C-reactive protein; and biological markers related to infection (including C-reactive protein, procalcitonin and others). We also identified systematic reviews that reported the accuracy of specific tests for influenza and respiratory syncytial virus. No reviews were found that assessed the diagnostic accuracy of white cell count for bacterial respiratory infection, or multiplex tests for influenza and respiratory syncytial virus. We therefore conducted searches for primary studies, and carried out meta-analyses for these index tests. Overall, we found that symptoms and signs have poor diagnostic accuracy for bacterial respiratory infection (sensitivity ranging from 9.6% to 89.1%; specificity ranging from 13.4% to 95%). Accuracy of biomarkers was slightly better, particularly when combinations of biomarkers were used (sensitivity 80-90%, specificity 82-93%). The sensitivity and specifici
背景：急性呼吸道感染是初级和急诊医疗服务中常见的就诊原因。识别细菌感染患者对于确保适当治疗至关重要。然而，避免过度处方抗生素以防止不必要的副作用和抗菌药耐药性也很重要。我们进行了一项系统性综述，总结了诊断成人细菌性呼吸道感染以及诊断两种常见呼吸道病毒（流感和呼吸道合胞病毒）的症状、体征和护理点检测诊断准确性的证据：主要方法是概述现有的系统综述。我们进行了文献检索（2023 年 5 月 22 日），以确定有关护理点检测诊断准确性的系统综述。在发现多篇综述的情况下，我们选择了最新、最全面的综述，其范围与我们的综述问题重合度最高。我们使用 "系统综述偏倚风险"（Risk of Bias in Systematic Reviews）工具对方法学质量进行了评估。提取诊断准确性（灵敏度、特异性或曲线下面积）的简要估计值。在未发现系统综述的情况下，我们搜索了主要研究。我们提取了足够的数据来构建诊断准确性的 2 × 2 表，以计算灵敏度和特异性。方法学质量采用诊断准确性研究质量评估第 2 版工具进行评估。在可能的情况下，我们进行了荟萃分析。我们使用 GRADE 评估现有综述和新分析中证据的确定性：我们确定了 23 篇综述涉及我们的综述问题；其中 6 篇被选为最全面且与我们的综述方案范围相似的综述。这些系统性综述考虑了细菌性呼吸道感染的以下检测方法：单个症状和体征；症状和体征组合（在临床预测模型中）；包含 C 反应蛋白的临床预测模型；以及与感染相关的生物标记物（包括 C 反应蛋白、降钙素原等）。我们还发现了报告流感和呼吸道合胞病毒特定检测准确性的系统性综述。我们没有发现评估细菌性呼吸道感染白细胞计数诊断准确性的综述，也没有发现评估流感和呼吸道合胞病毒多重检测准确性的综述。因此，我们检索了主要研究，并对这些指标检测进行了荟萃分析。总体而言，我们发现症状和体征对细菌性呼吸道感染的诊断准确性较低（敏感性从 9.6% 到 89.1%；特异性从 13.4% 到 95%）。生物标志物的准确性稍好，尤其是在使用生物标志物组合时（灵敏度为 80-90%，特异性为 82-93%）。不同类型检测对流感或呼吸道合胞病毒的敏感性和特异性差异很大。涉及核酸扩增技术的检测（单一病原体或多重检测）对流感的诊断准确率最高（灵敏度 91-99.8%，特异性 96.8-99.4%）：在使用 GRADE 进行评估时，大多数证据被认为确定性较低或非常低，原因包括效果估计不精确、可能存在偏差以及纳入了本综述范围之外的参与者（儿童或住院患者）：目前的证据不足以支持在初级和急诊护理中常规使用护理点检测。进一步的工作必须确定引入护理点检测是增加了价值，还是仅仅增加了医疗成本：本文是由美国国家健康与护理研究所（NIHR）健康技术评估项目资助的独立研究，获奖编号为NIHR159948。
{"title":"Diagnostic accuracy of point-of-care tests for acute respiratory infection: a systematic review of reviews.","authors":"Katie E Webster, Tom Parkhouse, Sarah Dawson, Hayley E Jones, Emily L Brown, Alastair D Hay, Penny Whiting, Christie Cabral, Deborah M Caldwell, Julian Pt Higgins","doi":"10.3310/JLCP4570","DOIUrl":"https://doi.org/10.3310/JLCP4570","url":null,"abstract":"<p><strong>Background: </strong>Acute respiratory infections are a common reason for consultation with primary and emergency healthcare services. Identifying individuals with a bacterial infection is crucial to ensure appropriate treatment. However, it is also important to avoid overprescription of antibiotics, to prevent unnecessary side effects and antimicrobial resistance. We conducted a systematic review to summarise evidence on the diagnostic accuracy of symptoms, signs and point-of-care tests to diagnose bacterial respiratory tract infection in adults, and to diagnose two common respiratory viruses, influenza and respiratory syncytial virus.</p><p><strong>Methods: </strong>The primary approach was an overview of existing systematic reviews. We conducted literature searches (22 May 2023) to identify systematic reviews of the diagnostic accuracy of point-of-care tests. Where multiple reviews were identified, we selected the most recent and comprehensive review, with the greatest overlap in scope with our review question. Methodological quality was assessed using the Risk of Bias in Systematic Reviews tool. Summary estimates of diagnostic accuracy (sensitivity, specificity or area under the curve) were extracted. Where no systematic review was identified, we searched for primary studies. We extracted sufficient data to construct a 2 × 2 table of diagnostic accuracy, to calculate sensitivity and specificity. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies version 2 tool. Where possible, meta-analyses were conducted. We used GRADE to assess the certainty of the evidence from existing reviews and new analyses.</p><p><strong>Results: </strong>We identified 23 reviews which addressed our review question; 6 were selected as the most comprehensive and similar in scope to our review protocol. These systematic reviews considered the following tests for bacterial respiratory infection: individual symptoms and signs; combinations of symptoms and signs (in clinical prediction models); clinical prediction models incorporating C-reactive protein; and biological markers related to infection (including C-reactive protein, procalcitonin and others). We also identified systematic reviews that reported the accuracy of specific tests for influenza and respiratory syncytial virus. No reviews were found that assessed the diagnostic accuracy of white cell count for bacterial respiratory infection, or multiplex tests for influenza and respiratory syncytial virus. We therefore conducted searches for primary studies, and carried out meta-analyses for these index tests. Overall, we found that symptoms and signs have poor diagnostic accuracy for bacterial respiratory infection (sensitivity ranging from 9.6% to 89.1%; specificity ranging from 13.4% to 95%). Accuracy of biomarkers was slightly better, particularly when combinations of biomarkers were used (sensitivity 80-90%, specificity 82-93%). The sensitivity and specifici","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-75"},"PeriodicalIF":3.5,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365067","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}
Jacqui Prieto, Jennie Wilson, Alison Tingle, Emily Cooper, Melanie Handley, Jo Rycroft-Malone, Jennifer Bostock, Lynne Williams, Heather Loveday
<p><strong>Background: </strong>Urinary tract infection is the most diagnosed infection in older people. It accounts for more than 50% of antibiotic prescriptions in care homes and is a frequent reason for care home residents being hospitalised.</p><p><strong>Objective: </strong>This realist review developed and refined programme theories for preventing and recognising urinary tract infection, exploring what works, for whom and in what circumstances.</p><p><strong>Design: </strong>The review used realist synthesis to explore existing literature on the detection and prevention of urinary tract infection, complemented by stakeholder consultation. It applies to the UK context, although other healthcare systems may identify synergies in our findings.</p><p><strong>Data sources: </strong>Bibliographic databases searched included MEDLINE, CINAHL, EMBASE, Cochrane Library, Web of Science Core Collection (including the Social Sciences Citation Index), Sociological Abstracts, Bibliomap and National Institute for Health and Care Research Journals Library.</p><p><strong>Data selection and extraction: </strong>Title and abstract screening were undertaken by two researchers independently of each other. Selection and assessment were based on relevance and rigour and cross-checked by a second researcher. Data extracted from the included studies were explored for explanations about how the interventions were considered to work (or not). Evidence tables were constructed to enable identification of patterns across studies that offered insight about the features of successful interventions.</p><p><strong>Data analysis and synthesis: </strong>Programme theories were constructed through a four-stage process involving scoping workshops, examination of relevant extant theory, analysis and synthesis of primary research, teacher-learner interviews and a cross-system stakeholder event. A process of abductive and retroductive reasoning was used to construct context-mechanism-outcome configurations to inform programme theory.</p><p><strong>Results: </strong>The scoping review and stakeholder engagement identified three theory areas that address the prevention and recognition of urinary tract infection and show what is needed to implement best practice. Nine context-mechanism-outcome configurations provided an explanation of how interventions to prevent and recognise urinary tract infection might work in care homes. These were (1) recognition of urinary tract infection is informed by skills in clinical reasoning, (2) decision-support tools enable a whole care team approach to communication, (3) active monitoring is recognised as a legitimate care routine, (4) hydration is recognised as a care priority for all residents, (5) systems are in place to drive action that helps residents to drink more, (6) good infection prevention practice is applied to indwelling urinary catheters, (7) proactive strategies are in place to prevent recurrent urinary tract infection, (8) care home l
资助：该奖项由国家健康与护理研究所（NIHR）健康技术评估计划（NIHR奖项编号：NIHR130396）资助，全文发表于《健康技术评估》第28卷第68期。如需了解更多奖项信息，请访问 NIHR Funding and Awards 网站。
{"title":"Strategies for older people living in care homes to prevent urinary tract infection: the StOP UTI realist synthesis.","authors":"Jacqui Prieto, Jennie Wilson, Alison Tingle, Emily Cooper, Melanie Handley, Jo Rycroft-Malone, Jennifer Bostock, Lynne Williams, Heather Loveday","doi":"10.3310/DADT3410","DOIUrl":"10.3310/DADT3410","url":null,"abstract":"<p><strong>Background: </strong>Urinary tract infection is the most diagnosed infection in older people. It accounts for more than 50% of antibiotic prescriptions in care homes and is a frequent reason for care home residents being hospitalised.</p><p><strong>Objective: </strong>This realist review developed and refined programme theories for preventing and recognising urinary tract infection, exploring what works, for whom and in what circumstances.</p><p><strong>Design: </strong>The review used realist synthesis to explore existing literature on the detection and prevention of urinary tract infection, complemented by stakeholder consultation. It applies to the UK context, although other healthcare systems may identify synergies in our findings.</p><p><strong>Data sources: </strong>Bibliographic databases searched included MEDLINE, CINAHL, EMBASE, Cochrane Library, Web of Science Core Collection (including the Social Sciences Citation Index), Sociological Abstracts, Bibliomap and National Institute for Health and Care Research Journals Library.</p><p><strong>Data selection and extraction: </strong>Title and abstract screening were undertaken by two researchers independently of each other. Selection and assessment were based on relevance and rigour and cross-checked by a second researcher. Data extracted from the included studies were explored for explanations about how the interventions were considered to work (or not). Evidence tables were constructed to enable identification of patterns across studies that offered insight about the features of successful interventions.</p><p><strong>Data analysis and synthesis: </strong>Programme theories were constructed through a four-stage process involving scoping workshops, examination of relevant extant theory, analysis and synthesis of primary research, teacher-learner interviews and a cross-system stakeholder event. A process of abductive and retroductive reasoning was used to construct context-mechanism-outcome configurations to inform programme theory.</p><p><strong>Results: </strong>The scoping review and stakeholder engagement identified three theory areas that address the prevention and recognition of urinary tract infection and show what is needed to implement best practice. Nine context-mechanism-outcome configurations provided an explanation of how interventions to prevent and recognise urinary tract infection might work in care homes. These were (1) recognition of urinary tract infection is informed by skills in clinical reasoning, (2) decision-support tools enable a whole care team approach to communication, (3) active monitoring is recognised as a legitimate care routine, (4) hydration is recognised as a care priority for all residents, (5) systems are in place to drive action that helps residents to drink more, (6) good infection prevention practice is applied to indwelling urinary catheters, (7) proactive strategies are in place to prevent recurrent urinary tract infection, (8) care home l","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 68","pages":"1-139"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463900","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}
Catherine A Moakes, Andrew W Bradbury, Zainab Abdali, Gareth R Bate, Jack Hall, Hugh Jarrett, Lisa Kelly, Jesse Kigozi, Suzanne Lockyer, Lewis Meecham, Smitaa Patel, Matthew Popplewell, Gemma Slinn, Jonathan J Deeks
<p><strong>Background: </strong>Chronic limb-threatening ischaemia with ischaemic pain and/or tissue loss.</p><p><strong>Objective: </strong>To examine the clinical and cost-effectiveness of a vein bypass-first compared to a best endovascular treatment-first revascularisation strategy in preventing major amputation or death.</p><p><strong>Design: </strong>Superiority, open, pragmatic, multicentre, phase III randomised trial.</p><p><strong>Setting: </strong>Thirty-nine vascular surgery units in the United Kingdom, and one each in Sweden and Denmark.</p><p><strong>Participants: </strong>Patients with chronic limb-threatening ischaemia due to atherosclerotic peripheral arterial disease who required an infra-popliteal revascularisation, with or without an additional more proximal infra-inguinal revascularisation procedure, to restore limb perfusion.</p><p><strong>Interventions: </strong>A vein bypass-first or a best endovascular treatment-first infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation strategy.</p><p><strong>Main outcome measures: </strong>The primary outcome was amputation-free survival. Secondary outcomes included overall survival, major amputation, further revascularisation interventions, major adverse limb event, health-related quality of life and serious adverse events.</p><p><strong>Methods: </strong>Participants were randomised to a vein bypass-first or a best endovascular treatment-first revascularisation strategy. The original sample size of 600 participants (247 events) was based on a hazard ratio of 0.66 with amputation-free survival rates of 0.72, 0.62, 0.53, 0.47 and 0.35 in years 1-5 in the best endovascular treatment-first group with 90% power and alpha at <i>p</i> = 0.05. The sample size was revised to an event-based approach as a result of increased follow-up time due to slower than anticipated recruitment rates. Participants were followed up for a minimum of 2 years. A cost-effectiveness analysis was employed to estimate differences in total hospital costs and amputation-free survival between the groups. Additionally, a cost-utility analysis was carried out and the total cost and quality-adjusted life-years, 2 and 3 years after randomisation were used.</p><p><strong>Results: </strong>Between 22 July 2014 and 30 November 2020, 345 participants were randomised, 172 to vein bypass-first and 173 to best endovascular treatment-first. Non-amputation-free survival occurred in 108 (63%) of 172 patients in the vein bypass-first group and 92 (53%) of 173 patients in the best endovascular treatment-first group [adjusted hazard ratio 1.35 (95% confidence interval 1.02 to 1.80); <i>p</i> = 0.037]. Ninety-one (53%) of 172 patients in the vein bypass-first group and 77 (45%) of 173 patients in the best endovascular treatment-first group died [adjusted hazard ratio 1.37 (95% confidence interval 1.00 to 1.87)]. Over follow-up, the economic evaluation discounted results showed that best endovascula
{"title":"Vein bypass first vs. best endovascular treatment first revascularisation strategy for chronic limb-threatening ischaemia due to infra-popliteal disease: the BASIL-2 RCT.","authors":"Catherine A Moakes, Andrew W Bradbury, Zainab Abdali, Gareth R Bate, Jack Hall, Hugh Jarrett, Lisa Kelly, Jesse Kigozi, Suzanne Lockyer, Lewis Meecham, Smitaa Patel, Matthew Popplewell, Gemma Slinn, Jonathan J Deeks","doi":"10.3310/YTFV4524","DOIUrl":"10.3310/YTFV4524","url":null,"abstract":"<p><strong>Background: </strong>Chronic limb-threatening ischaemia with ischaemic pain and/or tissue loss.</p><p><strong>Objective: </strong>To examine the clinical and cost-effectiveness of a vein bypass-first compared to a best endovascular treatment-first revascularisation strategy in preventing major amputation or death.</p><p><strong>Design: </strong>Superiority, open, pragmatic, multicentre, phase III randomised trial.</p><p><strong>Setting: </strong>Thirty-nine vascular surgery units in the United Kingdom, and one each in Sweden and Denmark.</p><p><strong>Participants: </strong>Patients with chronic limb-threatening ischaemia due to atherosclerotic peripheral arterial disease who required an infra-popliteal revascularisation, with or without an additional more proximal infra-inguinal revascularisation procedure, to restore limb perfusion.</p><p><strong>Interventions: </strong>A vein bypass-first or a best endovascular treatment-first infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation strategy.</p><p><strong>Main outcome measures: </strong>The primary outcome was amputation-free survival. Secondary outcomes included overall survival, major amputation, further revascularisation interventions, major adverse limb event, health-related quality of life and serious adverse events.</p><p><strong>Methods: </strong>Participants were randomised to a vein bypass-first or a best endovascular treatment-first revascularisation strategy. The original sample size of 600 participants (247 events) was based on a hazard ratio of 0.66 with amputation-free survival rates of 0.72, 0.62, 0.53, 0.47 and 0.35 in years 1-5 in the best endovascular treatment-first group with 90% power and alpha at <i>p</i> = 0.05. The sample size was revised to an event-based approach as a result of increased follow-up time due to slower than anticipated recruitment rates. Participants were followed up for a minimum of 2 years. A cost-effectiveness analysis was employed to estimate differences in total hospital costs and amputation-free survival between the groups. Additionally, a cost-utility analysis was carried out and the total cost and quality-adjusted life-years, 2 and 3 years after randomisation were used.</p><p><strong>Results: </strong>Between 22 July 2014 and 30 November 2020, 345 participants were randomised, 172 to vein bypass-first and 173 to best endovascular treatment-first. Non-amputation-free survival occurred in 108 (63%) of 172 patients in the vein bypass-first group and 92 (53%) of 173 patients in the best endovascular treatment-first group [adjusted hazard ratio 1.35 (95% confidence interval 1.02 to 1.80); <i>p</i> = 0.037]. Ninety-one (53%) of 172 patients in the vein bypass-first group and 77 (45%) of 173 patients in the best endovascular treatment-first group died [adjusted hazard ratio 1.37 (95% confidence interval 1.00 to 1.87)]. Over follow-up, the economic evaluation discounted results showed that best endovascula","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"28 65","pages":"1-72"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463897","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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