Health technology assessment最新文献

{"title":"Newborn screening for severe combined immunodeficiency in the NHS newborn blood spot screening programme: a systematic review.","authors":"Marie Westwood, Jonathan Emerson, Nigel Armstrong, Lisa Stirk","doi":"10.3310/GJMW5701","DOIUrl":"10.3310/GJMW5701","url":null,"abstract":"<p><strong>Background: </strong>Severe combined immunodeficiency is an inherited condition arising from mutations in at least 19 known genes. Severe combined immunodeficiency can be identified through screening, family history or clinical presentation. Severe combined immunodeficiency is usually asymptomatic at birth and presents, in infancy, as recurrent and frequently severe infections. Without treatment, severe combined immunodeficiency is usually fatal in the first year of life.</p><p><strong>Objectives: </strong>To summarise the available evidence relevant to newborn screening for severe combined immunodeficiency in the UK NHS newborn blood spot screening programme. Three research questions, concerning the accuracy of screening tests, the efficacy of early treatment and the acceptability of screening, were developed to address this objective.</p><p><strong>Methods: </strong>Eleven bibliographic databases were searched for relevant studies from 2011 to April 2024. Separate inclusion criteria were specified for each research question. Study selection, data extraction and assessment of methodological quality followed standard systematic review methods. A narrative synthesis of results is presented, structured by research question. No meta-analyses were conducted.</p><p><strong>Results: </strong>Most positive predictive values, calculated from reports of newborn blood spot screening programme experience, were between 3.6% and 26%. Screening algorithms incorporating repeat sampling in preterm babies appeared to reduce false positives due to prematurity. However, the large number of other conditions that can give rise to a positive screening result mean that the positive predictive value for severe combined immunodeficiency remains consistently poor. Two small studies reported that early diagnosis of severe combined immunodeficiency, via newborn blood spot screening or family history and following the introduction of newborn blood spot screening, respectively, was associated with non-statistically significant improvements in post-transplant survival. A third study analysed data on <i>n</i> = 902 United States patients with severe combined immunodeficiency collected over a 28-year period and reported the results of multivariable Cox regression analyses, adjusted for demographic disease-related and transplant-related variables found to be significant on univariate analysis, showing that diagnosis of severe combined immunodeficiency via newborn blood spot screening significantly improved survival compared to diagnosis via clinical presentation. Qualitative data from the publications included in this evidence summary were generally indicative of parental support for newborn blood spot screening for severe combined immunodeficiency, but was mainly derived from parents of healthy newborns.</p><p><strong>Limitations: </strong>The systematic review component of this evidence summary was limited by a restriction to full publications in the English language","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 45","pages":"1-118"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13284761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258033","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}

{"title":"Effectiveness of non-pharmacological interventions for fatigue in adults with long-term conditions: a synopsis of the EIFFEL mixed-methods evidence synthesis.","authors":"Joanna Leaviss, Andrew Booth, David Coyle, George Daly, Sarah Davis, Helen Dawes, Vincent Deary, Kritica Dwivedi, Jessica E Forsyth, Kate Fryer, Samantha McCormick, Marissa Martyn-St James, Julia Newton, Shijie Ren, Gillian Rooney, Anthea Sutton, Mon Mon-Yee, Christopher Burton","doi":"10.3310/GJCB1006","DOIUrl":"10.3310/GJCB1006","url":null,"abstract":"<p><strong>Background: </strong>Fatigue is common in many long-term medical conditions. Interventions to date have largely been in single conditions.</p><p><strong>Objective: </strong>To conduct a mixed-methods evidence synthesis of the clinical and cost-effectiveness and acceptability of non-pharmacological interventions for fatigue in adults with long-term medical conditions.</p><p><strong>Methods: </strong>Randomised controlled trials, cost-effectiveness studies, or qualitative studies of non-pharmacological interventions for fatigue in long-term medical conditions where fatigue was either a criterion for inclusion, the primary target of the intervention, or the primary or coprimary outcome. Studies of post-infectious, post-traumatic, cancer-related or idiopathic fatigue were excluded.</p><p><strong>Information sources: </strong>Searches used the MEDical Literature Analysis and Retrieval System, Excerpta Medica dataBASE, Cumulative Index to Nursing and Allied Health Literature, and American Psychological Association PsycInfo<sup>®</sup> (American Psychological Association, Washington, DC, USA) databases. We used systematic CLUSTER searching for qualitative studies and Epistemonikos for systematic reviews.</p><p><strong>Involvement of patients: </strong>We held three rounds of five focus groups involving people with fatigue in long-term conditions to ensure that assumptions in, and reporting of, the research had validity with the patient population.</p><p><strong>Risk of bias: </strong>Risk-of-bias assessment of all studies included in the network meta-analysis was undertaken using an adapted version 2 of the Cochrane risk-of-bias tool for randomised controlled trials.</p><p><strong>Synthesis of results: </strong>Clinical effectiveness evaluation used random effects network meta-analyses at three time points. The cost-effectiveness analysis involved a de novo analysis of interventions identified as clinically effective. The qualitative synthesis involved a thematic synthesis of primary studies of interventions and a mega-synthesis of reviews of patient experience of fatigue across different conditions. Focus groups were analysed by thematic analysis, and findings from all work packages were integrated in a final synthesis by the research team.</p><p><strong>Results: </strong>The clinical effectiveness review included 88 randomised controlled trials, involving 27 interventions, with 6636 participants included at end of treatment, 1849 in the short term and 2322 in the long term.</p><p><strong>Synthesis of results: </strong>Compared to usual care at long-term follow-up, cognitive-behavioural therapy-based interventions and physical activity promotion showed statistically significant reductions in fatigue (standardised mean difference -0.4, 95% credible interval -0.63 to -0.21, 9 studies; and -0.52, -0.86 to -0.18, 2 studies), respectively. Effective interventions provided positive net monetary benefit versus usual care, particularly when delivere","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 53","pages":"1-34"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345115","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}

{"title":"Plain balloon angioplasty +/- bare metal stenting versus drug-coated balloon angioplasty +/- bare metal stenting versus primary drug-eluting stenting in patients with chronic limb-threatening ischaemia: BASIL-3, an open-label, three-arm, randomised, multi-centre, phase 3 trial.","authors":"Matthew A Popplewell, Jack A Hall, Jesse Kigozi, Mishal Javed, Lewis Meecham, Gareth R Bate, Lisa Kelly, Jonathan J Deeks, Catherine A Moakes, Andrew W Bradbury","doi":"10.3310/GJAB0915","DOIUrl":"10.3310/GJAB0915","url":null,"abstract":"<p><strong>Objectives: </strong>To determine which primary endovascular revascularisation strategy represents the most clinical and cost-effective treatment for patients with chronic limb threatening ischaemia who require an endovascular femoro-popliteal, with or without an infra-popliteal revascularisation.</p><p><strong>Design: </strong>Three-arm open-label pragmatic multicentre randomised phase 3 superiority trial.</p><p><strong>Setting: </strong>Thirty-five UK NHS vascular units.</p><p><strong>Participants: </strong>Patients with chronic limb threatening ischaemia who required an endovascular femoro-popliteal with or without an infra-popliteal revascularisation.</p><p><strong>Interventions: </strong>Participants were randomly assigned (1 : 1 : 1) to either a femoro-popliteal plain balloon angioplasty with or without bare metal stenting (considered as control or reference), or a drug-coated balloon angioplasty with or without bare metal stenting, or a drug-eluting stenting first revascularisation strategy.</p><p><strong>Methods: </strong>The primary outcome was amputation-free survival defined as time to first major amputation or death from any cause. Secondary outcomes included overall survival, limb salvage, major adverse limb events, major adverse cardiac events and other pre-specified clinical and patient reported outcome measures. Serious adverse events were collected up to 30 days following the first revascularisation procedure.</p><p><strong>Results: </strong>Between 29 January 2016 and 31 August 2021, 481 participants [167 (35%) women] of mean age 71.8 years (standard deviation 10.8) were randomised. Major amputation or death occurred in 106 of 160 (66%) participants in the plain balloon angioplasty ± bare metal stenting group, 97 of 161 (60%) participants in the drug-coated balloon angioplasty ± bare metal stenting, and 93 of 159 (58%) participants in the drug-eluting stenting group [adjusted hazard ratios: plain balloon angioplasty ± bare metal stenting vs. drug-coated balloon angioplasty ± bare metal stenting: 0.84 (97.5% confidence interval 0.61 to 1.16), <i>p</i> = 0.22; plain balloon angioplasty ± bare metal stenting vs. drug-eluting stenting: 0.83 (97.5% confidence interval 0.60 to 1.15), <i>p</i> = 0.20]. There were no differences in serious adverse events between the groups. There were no differences in mortality when drug technology arms were pooled versus plain balloon angioplasty ± bare metal stenting. When compared to plain balloon angioplasty, drug-eluting stenting was less costly [-£724 (95% confidence interval -£4975 to £2631)] and resulted in additional 0.048 quality-adjusted life-years (95% confidence interval -0.060 to 0.148). Drug-coated balloon angioplasty was unlikely to be a cost-effective option (probability 52% of being cost-effective at £20,000 per quality-adjusted life-year) while drug-eluting stenting was potentially cost-effective (probability 76% of being cost-effective at £20,000 per quality-adjusted life","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 50","pages":"1-18"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360516","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}

{"title":"Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis: a synopsis of MS-STAT2, a multicentre, randomised controlled, double-blind, phase 3 clinical trial.","authors":"Thomas Williams, James Blackstone, Nevin John, Marie Braisher, Floriana De Angelis, Alessa Bianchi, Alberto Calvi, Anisha Doshi, Sean Apap Mangion, Charles Wade, Ekaterina Bordea, Rachel Merry, Gil Barton, Dawn Lyle, Elisabeth Jarman, Don Mahad, Abdullah Shehu, Tarunya Arun, Gavin McDonnell, Ruth Geraldes, Matthew Craner, Charles Hillier, Jeban Ganesalingam, Leonora Fisniku, Jeremy Hobart, Cord Spilker, Neil P Robertson, Seema Kalra, Stefano Pluchino, Sreedharan Harikrishnan, Miriam Mattoscio, Timothy Harrower, Carolyn Young, Martin Lee, Suresh Kumar Chhetri, Fayyaz Ahmed, David Rog, Eli Silber, Paul Gallagher, Martin Duddy, Agne Straukiene, Richard Nicholas, Claire Rice, Susan Tebbs, Annie Hawton, Rachael Hunter, Gavin Giovannoni, Olga Ciccarelli, Judy Beveridge, Stuart Nixon, Alan J Thompson, John Greenwood, Owen Pearson, Nikos Evangelou, Basil Sharrack, Ian Galea, Sue Pavitt, Siddharthan Chandran, Helen L Ford, Jennifer M Nicholas, Jeremy Chataway","doi":"10.3310/GJJC5820","DOIUrl":"10.3310/GJJC5820","url":null,"abstract":"<p><strong>Background: </strong>Despite the relative success of immuno-modulatory disease-modifying therapy in relapsing remitting multiple sclerosis, progressive worsening of disability remains a major problem, particularly for those with secondary progressive multiple sclerosis. Various underlying mechanisms are likely to contribute, augmented by comorbidities (such as vascular risk) and ageing. In the phase 2b MS-STAT trial, simvastatin (80 mg) (Sandoz Ltd, Camberley, UK) reduced the mean annualised whole brain atrophy rate by 43% compared to placebo in patients with secondary progressive multiple sclerosis (<i>p</i> = 0.003). We now report the phase 3, MS-STAT2 trial, with confirmed progression of disability as the primary outcome.</p><p><strong>Methods: </strong>A multicentre, phase 3, randomised, double-blind, placebo-controlled clinical trial was conducted at 31 UK neuroscience centres and district general hospitals. Secondary progressive multiple sclerosis participants aged 18-65 years were randomised 1 : 1 to oral simvastatin (80 mg), or matched placebo, based on a minimisation algorithm that incorporated the following factors: sex (male/female); age (< or ≥ 45 years); Expanded Disability Status Scale baseline score (≤ 5.5 or ≥ 6); whether participants were taking newly licensed (2017 onward) disease-modifying treatments for secondary progressive multiple sclerosis; and trial site. An independent and secure online randomisation service was used. All participants, site investigators and the trial co-ordinating team were blinded to treatment allocation. The Expanded Disability Status Scale was measured every 6 months and was compared to baseline scores, with remote data collection used when enforced by the COVID-19 pandemic. The primary outcome was time to Expanded Disability Status Scale-confirmed disability progression. Progression of disability was defined as an increase of at least one point on the Expanded Disability Status Scale if the baseline score was < 6, or an increase of 0.5 point if the baseline score was ≥ 6. The initial disability progression event was finalised as confirmed if the increase in Expanded Disability Status Scale score persisted at the next assessments ≥ 6 months later. Follow-up was for 36 months, or 54 months, for those without confirmed disability progression at 36 months who agreed to enter an optional blinded extension. An intention-to-treat analysis was carried out.</p><p><strong>Findings: </strong>The study was conducted between 10 May 2018 and 26 July 2024. There were 964 participants randomised, with 482 in the placebo group and 482 in the simvastatin group. 173 (35.9%) participants in the placebo group and 192 (39.8%) participants in the simvastatin group experienced Expanded Disability Status Scale-confirmed disability progression (adjusted hazard ratio = 1.13, 95% confidence interval 0.91 to 1.39, <i>p</i> = 0.263). No material differences in the secondary outcomes were observed. No major safety issu","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 55","pages":"1-41"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345177","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}

{"title":"PERsonalised Medicine for Intensification of Treatment (PERMIT) in type 2 diabetes mellitus: a target trial emulation from routine data.","authors":"David G Lugo-Palacios, Patrick Bidulka, Paul Charlton, Bill Huston, Anna Carnegie, Orlagh Carroll, Stephen O'Neill, Amanda I Adler, Anirban Basu, Richard J Silverwood, Andrew H Briggs, Liam Smeeth, Ian J Douglas, Kamlesh Khunti, Richard Grieve","doi":"10.3310/ASDB8011","DOIUrl":"10.3310/ASDB8011","url":null,"abstract":"<p><strong>Background: </strong>Evidence is required on the relative effectiveness of sulphonylureas, dipeptidyl peptidase-4 inhibitors or sodium-glucose cotransporter 2 inhibitors added to metformin for people with type 2 diabetes mellitus.</p><p><strong>Objectives: </strong>To assess disparities in the initiation of second-line antidiabetic treatments prescribed among people with type 2 diabetes mellitus in England according to ethnicity and social deprivation. To compare the effectiveness of sulphonylureas, dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter 2 inhibitors added to metformin for people with type 2 diabetes mellitus who require second-line treatment in routine clinical practice. To examine heterogeneity in the comparative short-term (12 months) effectiveness of sulphonylureas versus dipeptidyl peptidase-4 inhibitors combined with metformin on levels of glycated haemoglobin across the entire target population and subpopulations of decision-making relevance. To assess the comparative effectiveness of sulphonylureas, dipeptidyl peptidase-4 inhibitors or sodium-glucose cotransporter 2 inhibitors added to metformin according to individual risk-factor profiles of multiple long-term conditions. To calibrate the RAPIDS microsimulation model to UK data and then use the resultant RAPIDS-UK model to predict probabilities of long-term complications for people with type 2 diabetes mellitus in England after second-line treatment with sulphonylureas, dipeptidyl peptidase-4 inhibitors or sodium-glucose cotransporter 2 inhibitors added to metformin.</p><p><strong>Methods: </strong>We included adults with type 2 diabetes mellitus who initiated second-line antidiabetic treatment with sulphonylureas, dipeptidyl peptidase-4 inhibitors or sodium-glucose cotransporter 2 inhibitors added to metformin monotherapy. We used data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics and the Office of National Statistics. We applied target trial emulation and instrumental variable analyses to reduce the risks of biases, including confounding. The primary outcome was change in mean glycated haemoglobin (mmol/mol) at 1-year follow-up. Secondary outcomes: change in mean body mass index, systolic blood pressure, estimated glomerular filtration rate and time to major adverse kidney event, major adverse cardiovascular event, heart failure hospitalisation, eye disease, amputation and all-cause mortality. We assessed treatment effect heterogeneity according to multiple long-term conditions. We used a microsimulation model to report the impact on long-term complications.</p><p><strong>Results: </strong>After the instrumental variable analysis, the mean 95% confidence interval differences in glycated haemoglobin change between baseline and 1 year were: -2.5 mmol/mol (-3.7 to -1.3) for sodium-glucose cotransporter 2 inhibitors versus sulphonylureas, and -3.2 mmol/mol (-4.6 to -1.8) for sodium-glucose cotransporter 2 inhibitor","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 47","pages":"1-28"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13266498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148175834","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}

{"title":"Treatments for metastatic non-small cell lung cancer: a pathways pilot with systematic review, evidence synthesis and economic model.","authors":"Hugo Pedder, Catalina Lopez Manzano, Lindsay Claxton, Penny Whiting, Lucy Beggs, Ayman Sadek, Kusal Lokuge, Eve Tomlinson, Chris Cooper, Rachel James, Yuanyuan Zhang, Robert Willans, Laura Webster, Joe Carroll, David Phillippo, David Wonderling, Adam Dangoor, Dharmisha Chauhan, Stella O'Brien, Nicky J Welton","doi":"10.3310/GJNW3422","DOIUrl":"10.3310/GJNW3422","url":null,"abstract":"<p><strong>Background: </strong>National Institute for Health and Care Excellence technology appraisals assess the effectiveness and cost-effectiveness of medicines at a single point in the treatment pathway. However, for some disease areas, such as non-small cell lung cancer, there are many recommendations, making it difficult to use National Institute for Health and Care Excellence guidance. The treatment pathway for metastatic stage 4 non-small cell lung cancer can be divided into decision points (nodes) based on histology (squamous or non-squamous), programmed death-ligand 1 expression, presence of tumour mutations and line of therapy. The National Institute for Health and Care Excellence commissioned this pilot to assess the potential of taking a 'pathways approach' to technology appraisals. The aim was to build a single disease-specific cost-effectiveness model for metastatic stage 4 non-small cell lung cancer patients not eligible for targeted therapies at first line, that can be updated with economic and clinical data as required.</p><p><strong>Methods: </strong>We conducted a systematic review (searches last updated 11 July 2025) and network meta-analysis of treatment efficacy and safety at each decision node in the pathway. We used flexible fractional polynomial models for primary outcome progression-free survival, required for a model of treatment sequences. We built a novel cost-effectiveness model that compared sequences of treatments, and was populated using network meta-analyses for progression-free survival, data on overall survival after last-line therapy, evidence on treatment sequences from an analysis of systemic anticancer therapy data, and quality of life, cost and resource use estimates from previous technology appraisals. Drug list prices were used, but confidential discounts are available.</p><p><strong>Results: </strong>We included 15 randomised controlled trials and 1 single-arm study in the review, judged as some concerns or low risk of bias. Immunotherapies, in combination with doublet platinum chemotherapy, were most effective first-line treatments, although with higher adverse event rates. Immunotherapy monotherapies were most effective at second line, unless patients were suitable for targeted therapies. Sequences starting with atezolizumab + bevacizumab + doublet platinum chemotherapy had similar costs and quality-adjusted life-years to sequences starting with pembrolizumab + doublet platinum chemotherapy. Sequences starting with pemetrexed + platinum chemotherapy had the lowest costs but also the lowest total quality-adjusted life-years.</p><p><strong>Sequences for non-squamous non-small cell lung cancer, programmed death-ligand 1 ≥ 50%: </strong>Sequences starting with pembrolizumab + doublet platinum chemotherapy had highest quality-adjusted life-years, but higher costs compared to other sequences. Sequences starting with pemetrexed + platinum chemotherapy had the lowest cost and the lowest number of quality-ad","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 46","pages":"1-319"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13266499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148162773","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}

{"title":"Placental growth factor (PLGF)-based testing to help diagnose suspected pre-eclampsia: a systematic review and economic evaluation.","authors":"Jonathan Shepherd, Geoff Frampton, Ben Kearns, Karen Pickett, Inês Souto-Ribeiro, Allan J Wailoo, Lois Woods, Keith Cooper, Lorna Hazell, Abdullah Pandor, David A Scott","doi":"10.3310/HDST9104","DOIUrl":"10.3310/HDST9104","url":null,"abstract":"<p><strong>Background: </strong>Predicting a diagnosis of pre-eclampsia is based on a combination of clinical assessment of blood pressure, presence of protein in the urine, symptoms and laboratory test abnormalities. Accurately detecting pre-eclampsia is important to avoid false-positive diagnoses which could lead to unnecessary antenatal admissions and/or preterm delivery. Four blood tests that measure the biomarkers of placental growth factor or the ratio of soluble fms-like tyrosine kinase-1 to placental growth factor are available (known as Triage, Elecsys, DELFIA Xpress, and BRAHMS Kryptor tests). Abnormal measurements of these biomarkers can be used as an aid to predict a diagnosis of pre-eclampsia and maternal and fetal outcomes.</p><p><strong>Objectives: </strong>To evaluate the test accuracy, clinical effectiveness and cost-effectiveness of placental growth factor -based tests used in conjunction with standard clinical assessment for predicting pre-eclampsia and maternal and fetal outcomes in pregnant women who are referred to secondary care with suspected pre-eclampsia in weeks 20-37 of pregnancy.</p><p><strong>Data sources and methods: </strong>A systematic review of the diagnostic/prognostic accuracy and clinical effectiveness of placental growth factor-based tests with standard clinical assessment. Database included MEDical Literature Analysis and Retrieval System, Excerpta Medica dataBASE and Cochrane Library. Other sources searched included relevant conference proceedings and websites, grey literature and research in progress. The most recent date of searching was 18 March 2021. An independent economic analysis was conducted using a decision tree model. The model includes short-term costs and quality-adjusted life-years for the management of women, maternal and neonatal outcomes and long-term outcomes for severe neonatal complications. The model compared the use of the test alongside standard clinical assessment to standard clinical assessment only. Two different estimates of standard clinical assessment were included, from the INSPIRE study and from National Institute of Health and Care Excellence Diagnostic Guidance 23.</p><p><strong>Results: </strong>Seventeen studies were included in the systematic review. Two large, randomised trials provided the best available evidence to inform the economic model: The PARROT trial (Triage test) and the INSPIRE trial (Elecsys test). When used as rule-out tests for pre-eclampsia (with neonatal outcomes included), all four tests produced higher quality-adjusted life-years and higher costs than both types of standard clinical assessment. The incremental cost per quality-adjusted life-year ranged from £637 (DELFIA test vs. standard clinical assessment from INSPIRE) to £47,393 (Triage test vs. standard clinical assessment from diagnostics guidance 23) per quality-adjusted life-year. Incremental costs and quality-adjusted life-years were always very small, with incremental costs always less than t","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 54","pages":"1-160"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345175","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}

{"title":"Effectiveness of psychosocial interventions for adults with substance use disorder that have a co-occurring mental health disorder: an umbrella review and illustrative cost-effectiveness analysis.","authors":"Emma Simpson, Sunhong Kwon, Munira Essat, Ruth Wong, Shijie Ren, Sarah Stacey, Edward Day, Matt Stevenson","doi":"10.3310/GJES1821","DOIUrl":"10.3310/GJES1821","url":null,"abstract":"<p><strong>Objectives: </strong>To systematically review evidence of the clinical effectiveness of psychosocial interventions for adults with substance use disorder that have a co-occurring common mental health disorder or borderline personality disorder. To identify papers that estimate the cost-effectiveness of interventions for patients with substance use disorder and common mental health disorder or borderline personality disorder.</p><p><strong>Methods: </strong>An umbrella review (a systematic review of systematic reviews) for clinical effectiveness was conducted. Systematic database searches [MEDLINE, EMBASE, PsycInfo<sup>®</sup> (American Psychological Association, Washington, DC, USA), Cochrane Database of Systematic Reviews, and Web of Science] were carried out in February 2024. Inclusion criteria: Adults with substance use disorder and common mental health disorder or borderline personality disorder; psychosocial interventions (with or without pharmacological therapies); comparators psychosocial treatments, treatment as usual, waitlist/no treatment; systematic reviews of randomised controlled trials. Data, including critical appraisal, were extracted into a standardised form by one reviewer, and checked by another. Data were discussed in a narrative review. A literature review of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and EconLit were undertaken to identify cost-effectiveness papers. An illustrative model was constructed to show how cost-effectiveness could be calculated if data were available.</p><p><strong>Results: </strong>Of 5420 unique records, 30 systematic reviews were included in the clinical review. The methodological quality of the reviews was generally good. Most of the interventions and many of the active comparators studied resulted in some improvement for patients. Most reviews focused on depression, anxiety or post-traumatic stress disorder; there were some looking at mixed common mental health disorder or borderline personality disorder. There was much heterogeneity both between reviews, and between the randomised controlled trials within the reviews. The results suggested integrated treatment for co-occurring diagnosis patients may be better for common mental health disorder outcomes than treatment as usual of parallel uncoordinated services. One study was identified that met the cost-effectiveness criteria. However, this reported results alongside a clinical study and was not a modelling paper. The illustrative model should aid future researchers.</p><p><strong>Limitations: </strong>Heterogeneity made it difficult to reach an overall conclusion about which therapies were best. Most reviews stated the results were not generalisable across all populations or settings. There were few reviews of borderline personality disorder; or of common mental health disorder other than anxiety/depression/post-traumatic stress disorder.</p><p><strong>Future works: </strong>Future research comparing integrated with p","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 49","pages":"1-141"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360432","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}

{"title":"An exploration of the factors influencing successful implementation, delivery and outcomes in an intensive care sedation study: process evaluation of the A2B RCT.","authors":"Leanne M Aitken, Lydia M Emerson, Kalliopi Kydonaki, Bronagh Blackwood, Ben Creagh-Brown, Nazir Lone, Cathrine McKenzie, Richard Parker, Michael C Reade, Christopher J Weir, Matt P Wise, Timothy S Walsh","doi":"10.3310/GJTW0620","DOIUrl":"10.3310/GJTW0620","url":null,"abstract":"<p><strong>Background: </strong>Choice of sedation of critically ill patients is a core element of intensive care practice. The alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B) trial tested the effectiveness of two alpha agonist sedatives versus propofol in reducing time on mechanical ventilation in 38 intensive care units in the United Kingdom. To evaluate both how this complex trial was implemented and how this may have influenced trial outcomes, an understanding of the contextual and practice variation across multiple sites was required.</p><p><strong>Aim and objectives: </strong>The aim of this process evaluation of the A2B trial was to determine how the intervention was delivered, the extent to which it was delivered as intended and the impact this had on outcomes. Specifically, we aimed to: Establish the degree to which the A2B intervention was delivered as intended, specifically in relation to fidelity, dose and reach across patients. Understand factors that impacted on successful delivery of both the A2B intervention and trial, in relation to attitudes and perceptions of staff, including context and standard care.</p><p><strong>Design and methods: </strong>A mixed-methods, multiphase design was used following extensive pre-trial exploration of current practice. Quantitative data were drawn from the main trial database covering 38 sites to assess the intervention's fidelity, dose and reach in each site. Data were analysed descriptively and provided a low-moderate-high rating. Qualitative data were collected by interviews mid trial (phase 1) and end of trial (phase 2). Participants were recruited from a random sample of 30 intensive care units active at the time of sampling and included the principal investigator, research nurses and clinical staff. Semistructured interviews, informed by the trial's logic model, lasted 45-60 minutes. Data collection focused on whether the intervention could be delivered as intended, factors that impacted upon successful delivery and understanding intervention adherence. Analysis used a framework approach based on the logic model. Data collection and qualitative analyses were completed prior to knowing the primary results of the trial.</p><p><strong>Results: </strong>Site intervention adherence ratings for fidelity, dose and reach were low (4), moderate (20) and high (14). Participants from 12 intensive care units in each of phase 1 (33 staff) and phase 2 (36 staff) provided qualitative data; participating intensive care units differed between phases. Factors identified in phase 1 focused on intervention delivery and trial conduct and incorporated both organisational and participant-related factors. In phase 2, participant-related factors included clinician preference, individual equipoise, clinician resistance and staff capability and capacity, while A2B trial-related factors included concerns relating to safety and side effects, overnight deep sedation practice, patient ","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"95-112"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523346","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}

{"title":"Digital front door technologies to pre-assess people before assessment for NHS Talking Therapies [HTE10055]: early value assessment.","authors":"Nigel Fleeman, James Mahon, Samuel Bryning, Sophie Beale, Angela Boland, Janette Greenhalgh, Yenal Dundar","doi":"10.3310/GJAB1822","DOIUrl":"10.3310/GJAB1822","url":null,"abstract":"<p><strong>Background: </strong>NHS Talking Therapies for anxiety and depression is a service that provides people in England with psychological support. There are several referral routes into the service, digital front door technologies being the most recent addition.</p><p><strong>Aim: </strong>The aim of this National Institute for Health and Care Excellence early value assessment was to map available evidence, assess potential benefits and costs of NHS Talking Therapies referral pathways with and without digital front door technologies, and identify evidence gaps to help direct future data collection and further research.</p><p><strong>Methods: </strong>The External Assessment Group carried out a systematic literature review (December 2024) to gather evidence relating to Limbic Access (Limbic), Wysa Digital Referral Assistant (Wysa), Censeo Digital (Psyomics) and AskFirst (Sensely). Information was collected across four broad outcome categories: accuracy and acceptability, resource and system impact, patient-reported outcomes, and costs. All study types were eligible for inclusion in the systematic literature review, along with evidence provided by the manufacturers of digital front door technologies (via requests for information). In addition, the External Assessment Group interviewed and sent questionnaires to stakeholders, including National Institute for Health and Care Excellence Specialist Committee Members, and carried out exploratory analyses of costs and benefits.</p><p><strong>Results: </strong>Evidence was only available for two digital front door technologies: Limbic Access and Wysa Digital Referral Assistant. Literature meeting the systematic literature review eligibility criteria comprised two published peer-reviewed studies, six unpublished studies and five requests for information responses. The strongest evidence related to accessibility and overall satisfaction with Limbic Access. Results from one peer-reviewed study showed that Limbic Access increased the number of referrals to NHS Talking Therapies versus services that did not implement the technology (odds ratio = 1.10, 95% confidence interval 1.075 to 1.131); this included an increase in access for some minority groups [Asian (odds ratio = 1.29; confidence interval 1.163 to 1.422), Black (odds ratio = 1.35, confidence interval 1.183 to 1.551) and non-binary (odds ratio = 2.95; confidence interval 2.065 to 4.206)]. Overall satisfaction reported by users who completed the Limbic Access referral process was high (≥ 89%). Resource impact evidence was provided by one peer-reviewed study; results showed that Limbic Access reduced clinical assessment duration by 12.7 minutes. No relevant information on quality and accuracy was identified.</p><p><strong>Interviews and questionnaires: </strong>Respondents were positive about digital front door technologies, suggesting that these tools could lead to better quality and more accurate (1) pre-referral practices and (2) initial clinic","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 52","pages":"1-138"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345194","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}