Background and ObjectivesDisorders of gut-brain interaction are highly prevalent and burdensome conditions for both patients and healthcare systems. Given the limited effectiveness of pharmacotherapy in treating disorders of gut-brain interaction, non-pharmacological interventions are increasingly used; however, the value for money of non-pharmacological treatments is uncertain. This is the first review to assess the economic evaluation evidence of non-pharmacological interventions for disorders of gut-brain interaction.MethodsA scoping review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Reporting adhered to ISPOR's good practices for systematic reviews with cost and cost-effectiveness outcomes. Comprehensive searches were performed on 24 October, 2023, and an updated search was run on 18 May, 2024 in PubMed/MEDLINE, Embase, Web of Science, Scopus and the International HTA database, with two reviewers screening studies in parallel. The novel Criteria for Health Economic Quality Evaluation (CHEQUE) framework was used to assess methodological and reporting quality. Reporting quality was further assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022.ResultsFifteen studies were included. Most studies examined treatments for irritable bowel syndrome. Cognitive behavioural therapy, dietary interventions and sacral neuromodulation were cost effective. Acupuncture and physiotherapy were not. CHEQUE assessment showed 12 studies met at least 70% of the methodological criteria, and 14 studies achieved 70% or more for reporting quality.ConclusionsThis review highlights gaps in the current evidence base, particularly in the robustness and generalisability of results due to methodological inconsistencies. Future research should incorporate longer follow-ups, comprehensive cost assessments, subgroup analyses, equity considerations and clearer justifications for modelling assumptions.

Hepatocellular carcinoma is one of the leading causes of cancer deaths globally and a key hindrance to extending life expectancy. Celastrol (CEL) demonstrates excellent antitumor activity, but faces challenges like low solubility and a narrow therapeutic window, limiting its clinical application. To address these limitations, drug combinations and nano-delivery systems have emerged as effective solutions. Curcumin (CUR), known for its antitumor and hepatoprotective effects, also exhibits good biocompatibility and the ability to mitigate drug-induced liver injury. Considering the complementary properties of CEL and CUR, including CEL's potent antitumor activity and CUR's hepatoprotective effects, we developed a novel self-assembling nanodrug delivery system (CCPN) for the co-loading of both compounds. CCPN nanoparticles were constructed through non-covalent interactions, including hydrogen bonding, π-π stacking, and electrostatic forces, which confer good stability and significantly enhance the solubility and bioavailability of CEL and CUR. Extensive in vitro and in vivo experiments demonstrated that CCPN effectively reduced CEL-induced hepatotoxicity in zebrafish and mouse models, exhibiting good biosafety. Additionally, CUR's fluorescence provides a unique advantage for real-time monitoring of drug distribution and release, facilitating the tracking of therapeutic progress. Furthermore, CCPN nanoparticles enhanced delivery efficiency in HepG2 cells, exhibiting superior anti-liver tumor outcomes, which are associated with the promotion of apoptosis in tumor cells. This study presents CCPN as a promising therapeutic strategy for hepatocellular carcinoma, integrating reduced hepatotoxicity, self-monitoring capabilities, and superior therapeutic efficacy.

Background: The economic and public health benefits of adult pneumococcal vaccines vary across countries due to different epidemiology and costs. We systematically reviewed and summarized findings and assumptions of cost-effectiveness analyses (CEA) of the recently introduced 15- and 20-valent pneumococcal conjugate vaccines (PCV15 and PCV20) in adults. Methods: We performed a systematic search for CEA studies of PCV15 and/or PCV20 versus existing strategies via PubMed, EMBASE, CEA Registry, EconLit, HTA Database, and NITAG resource center through April 23, 2024. Study characteristics, methods, assumptions, and findings were extracted independently by two reviewers; quality was assessed using ECOBIAS. Results were synthesized qualitatively to summarize key attributes and conclusions. Results: Of 137 identified records, 26 studies were included; the majority (24/26) concerned high-income countries. All employed static Markov-type models comparing higher-valent PCVs used alone or in combination with 23-valent pneumococcal polysaccharide vaccine (PPSV23) to current recommendations (PPSV23 alone, PCV13 alone, PCV13 + PPSV23, no vaccination). Most studies (22/26) concluded PCV20 used alone was cost-saving (dominant) or cost-effective compared to other adult pneumococcal strategies (PPSV23 alone, PCV13 ± PPSV23, PCV15 ± PPSV23, or no vaccination). PCVs were generally assumed to have serotype-specific effectiveness equal to PCV13 efficacy in the pivotal trial, though four studies used estimates from a Delphi panel; protection was assumed to last between 10 and 20 years. PPSV23 was assumed to have lower effectiveness against non-bacteremic pneumonia and shorter duration of protection. Herd effects from higher-valent PCVs in childhood (12/26), serotype replacement (2/26), or both (1/26) were included in half (13/26) of studies, which attenuated adult vaccine impact. Most studies were assessed as low risk of bias; five abstracts did not provide sufficient information for assessment. Conclusion: Current evidence indicates that 20-valent PCV used alone is likely to be cost-effective or dominate other adult pneumococcal strategies. Future research is needed to address remaining uncertainties in assumptions and to support evidence-based policymaking.

Background and objective: Robotic-assisted radical prostatectomy (RARP) is a surgical option for localized prostate cancer. Cost-effectiveness analysis (CEA) findings are inconsistent when comparing it with open (ORP) and laparoscopic (LRP) radical prostatectomy approaches. We performed a systematic review and meta-analysis to pool the incremental net benefit (INB) of these approaches. Methods: Relevant CEA studies of RARP were identified by searching the PubMed, Embase, Scopus, International Health Technology Assessment database, Tufts CEA Registry, and Centre for Reviews and Dissemination databases from January 2005 to October 2023. To be included, studies must compare costs, and quality- adjusted life years (QALYs) of RARP versus ORP or LRP, and report the incremental cost per QALY gained. Study characteristics, economic model, costs, and outcomes were extracted. INBs were calculated in 2022 US dollars adjusted for purchasing power parity. A pooled analysis was performed using a random-effect model stratified by country income level. Heterogeneity was assessed using the Q test and I2 statistic. Key findings and limitations: Thirteen studies with 17 comparisons, ten from high- income (HICs) and three from middle-income (MICs) countries, were included. Ten and five studies compared RARP with ORP and LRP, respectively. From a payer perspective, RARP was cost effective but not statistically significant compared with LRP in HICs (pooled INB: $7507.83 [-$1193.03 to $16 208.69], I2 = 81.15%) and not cost effective in MICs (%; -$4499.39 [-$16 500 to $7526.87], I2 = 17.15%). RARP showed no statistically significant cost effectiveness over ORP in both HICs ($3322.38 [-$1864.39 to $8509.15], I2 = 90.89%) and MICs ($2222.60 [-$2960.64 to $7405.83], I2 = 58.92%). Conclusions and clinical implications: RARP is cost effective compared with LRP in HICs but lacks statistical significance. When compared with ORP, RARP is not cost effective in HICs and MICs. Our findings may support decision-making for prostate cancer treatment options in countries with different health care systems, especially those with limited resources. Patient summary: Our systematic review and meta-analysis provide important information regarding robotic-assisted radical prostatectomy (RARP) compared with open (ORP) and laparoscopic (LRP) radical prostatectomy. In high-income countries, RARP is generally cost effective compared with LRP, but not with ORP, while in middle-income countries, RARP is not cost effective compared with LRP or ORP. The findings of this review can support decision-making for prostate cancer treatment options. (c) 2025 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background: Lifestyle interventions have been acknowledged as effective strategies for preventing type 2 diabetes mellitus (T2DM). However, the accessibility of conventional face-to-face interventions is often limited. Digital health intervention has been suggested as a potential solution to overcome the limitation. Despite this, there remains a significant gap in understanding the effectiveness of digital health for individuals with prediabetes, particularly in reducing T2DM incidence and reverting to normoglycemia. Objective: This study aimed to assess the effectiveness of different intervention modes of digital health, face-to-face, and blended interventions, particularly the benefits of digital health intervention, in reducing T2DM incidence and facilitating the reversion to normoglycemia in adults with prediabetes compared to the usual care. Methods: We conducted a comprehensive search in 9 electronic databases, namely MEDLINE, Embase, ACP Journal Club, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Cochrane Clinical Answers, Cochrane Methodology Register, Health Technology Assessment, and NHS Economic Evaluation Database through Ovid, from the inception to October 2024. This review included randomized controlled trials (RCTs) that studied the effectiveness of lifestyle interventions in adults with prediabetes. The overall intervention effect was synthesized using a random-effects model. The I² statistic was used to assess heterogeneity across the RCTs. We performed a subgroup analysis to explore the effectiveness of digital health, face-to-face, and blended interventions compared with the control group, which received usual care. Results: From an initial 7868 records retrieved from 9 databases, we identified 54 articles from 31 RCTs. Our analysis showed that face-to-face interventions demonstrated a significant 46% risk reduction in T2DM incidence (risk ratio [RR] 0.54, 95% CI 0.47-0.63; I²=43%; P<.001), and a 46% increase in the reversion to normoglycemia (RR 1.46, 95% CI 1.11-1.91; I²=82%; P=.006), when compared with the control group. On the other hand, digital health interventions, compared with the control group, were associated with a 12% risk reduction in T2DM incidence (RR 0.88, 95% CI 0.77-1.01; I²=0.6%; P=.06). Moreover, the blended interventions combining digital and face-to-face interventions suggested a 37% risk reduction in T2DM incidence (RR 0.63, 95% CI 0.49-0.81;I²<0.01%; P<.001) and an 87% increase in the reversion to normoglycemia (RR 1.87, 95% CI 1.30-2.69; I²=23%; P=.001). However, no significant effect on the reversal of prediabetes to normoglycemia was observed from the digital health interventions. Conclusions: Face-to-face interventions have consistently demonstrated promising effectiveness in both reductions in T2DM incidence and reversion to normoglycemia in adults with prediabetes. However, the effectiveness of digital health interventions in these areas has not been sufficiently proven. Given these results, further research is required to provide more definitive evidence of digital health and blended interventions in T2DM prevention in the future. Trial registration: PROSPERO CRD42023414313; https://tinyurl.com/55ac4j4n.

Background: Non-proliferative and proliferative diabetic retinopathy are common complications of diabetes and a major cause of sight loss. Anti-vascular endothelial growth factor drugs represent a treatment option for people with diabetic retinopathy and are routinely used to treat various other eye conditions. However, anti-vascular endothelial growth factor drugs are expensive relative to current care options, and it is unclear whether this additional cost is justified when the immediate risk of vision loss is lower compared to patients with more aggressive ophthalmological conditions. Objective: To systematically review the evidence supporting the cost-effectiveness of alternative treatments for diabetic retinopathy. Methods: A systematic review of all comparative cost-effectiveness studies evaluating any treatment for diabetic retinopathy was conducted. Bibliographic searches were carried out to identify studies reporting on the cost-effectiveness of treatments for diabetic retinopathy; the latest searches were conducted on 28 April 2023. Included studies were synthesised narratively and evaluated with reference to UK decision-making. Studies were grouped by population into non-proliferative diabetic retinopathy and proliferative diabetic retinopathy. Results: The review identified five studies in the proliferative diabetic retinopathy population, all of which examined the cost-effectiveness of anti-vascular endothelial growth factor treatments compared to pan-retinal photocoagulation. Results of these studies suggest that anti-vascular endothelial growth factor treatments offer some additional benefits in terms of preserved visual acuity but also incur substantial additional costs relative to pan-retinal photocoagulation. Most authors agreed that the additional costs outweigh the limited benefits, especially in certain patient subgroups without pre-existing oedema. As most of the identified evidence considered a US perspective, it is unclear how these results would translate to a UK setting. Two studies were identified in the non-proliferative diabetic retinopathy population. There was limited evidence to support the early use of anti-vascular endothelial growth factor treatment. However, one UK study suggested that early treatment of non-proliferative diabetic retinopathy with pan-retinal photocoagulation is cost-effective compared to delayed pan-retinal photocoagulation. Conclusions: Overall, there is a dearth of cost-effectiveness evidence considering the UK context. The identified studies raised doubts about the cost-effectiveness of anti-vascular endothelial growth factor treatments for proliferative diabetic retinopathy. No conclusions can be made regarding the cost-effectiveness of anti-vascular endothelial growth factor treatments for non-proliferative diabetic retinopathy. Future research should focus on developing rigorous model-based cost-effectiveness analyses integrating all available evidence. Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR132948.

Background: Mobile health interventions that utilize artificial intelligence may provide way for underserved populations to engage with healthcare. Purpose: Examine the policy considerations that must be deliberated when developing, regulating, implementing, and sustaining mHealth apps among historically underserved individuals. Methods: Reproductive Justice was used to investigate policy considerations for those with criminal legal system supervision who engage with mHealth apps. Three policy considerations resulted: 1) improving the legislative and regulatory landscape of digital technology, 2) enhancing comprehensive data protection legislation, 3) heightening privacy protections. Discussion: The need to bring awareness to policy protections on the local, institutional, state, federal, and global levels specific to mHealth apps among underserved groups with criminal legal supervision is required. Conclusion: These emerging advances in technology serve as an avenue for direct healthcare services to collaborate with other professions and organizations to implement ethical interventions that respect human rights and improve reproductive health equity.

Polymeric nanoparticles are among the most widely used nanocarriers for delivering therapeutic molecules. However, their synthesis processes often generate undesirable impurities that could be toxic and challenging to eliminate. In this study, we compared three purification techniques - centrifugation, dialysis, and tangential flow filtration (TFF) - to evaluate their efficacy in removing residual drug, surfactant, and solvent while preserving the nanoparticles' physicochemical features (hydrodynamic size, zeta potential, polydispersity index). Centrifugation excels in eliminating unencapsulated drug and residual surfactant but significantly affects the nanoparticles' physicochemical properties, such as colloidal stability and size homogeneity. On the other hand, dialysis is a gentler technique effective in removing residual solvent but less so for residual surfactant and unencapsulated drug. TFF emerges as a balanced approach, offering a compromise between the two but none of these techniques achieves satisfactory purification at lab-scale alone. While each technique has its merits, none can meet all requirements independently. The optimal purification strategy often involves a combination of techniques, determined on a case-by-case basis considering factors like purity levels, time, costs, and the preservation of critical properties such as drug loading and colloidal stability. This study underscores the need for a nuanced approach in selecting purification strategies for polymeric nanoparticles in drug delivery applications.

Background Obinutuzumab was approved in China in June 2021 used in combination with chemotherapy (followed by obinutuzumab maintenance) for the treatment of adult patients with previously untreated stage II bulky, III, or IV follicular lymphoma (FL). The clinical application of obinutuzumab has recently begun in China, but there is a lack of evidence to determine under which circumstances it should be considered the treatment of choice. A comprehensive assessment is necessary to evaluate the efficacy, safety, and cost-effectiveness of obinutuzumab in adult patients with FL.Objective To summarize the evidence on the efficacy, safety, and cost-effectiveness of obinutuzumab in adult patients with FL, aiming to provide medical professionals with evidence for informed choices in clinical practice.Methods The approach to this evidence synthesis was a rapid review of systematic reviews/meta-analyses (SR/meta-analyses), health technology assessment (HTA) reports, and pharmacoeconomic studies that brings together and summarizes the efficacy, safety, and cost-effectiveness of obinutuzumab in adult patients with FL. A literature search was conducted across multiple databases, including PubMed, Embase, Wanfang, CNKI, Weipu database, the Cochrane Library, the Centre for Reviews and Dissemination (CRD) database, International Network of Agencies for Health Technology Assessment (INAHTA) and Canada's Drug Agency (CDA-AMC), International Society for Pharmacoeconomics and Outcomes Research (ISPOR), National Institute For Health and Care Excellence (NICE), Institute For Clinical And Economic Review (ICER), Grey Literature Database and Grey Net International. The studies on obinutuzumab for FL were searched in full text with obinutuzumab, systematic review, meta-analysis, economics, cost, and health technology assessment as keywords, with a search time frame from the date of database creation to 29 November 2024. The literature was screened based on predefined inclusion and exclusion criteria, and data were meticulously extracted and synthesized by two authors. Simultaneously, the quality of the literature was thoroughly assessed.Results Obinutuzumab based chemotherapy (the chemotherapy regimen-cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); cyclophosphamide, vincristine, and prednisone (CVP); or bendamustine) significantly prolonged progression free survival (PFS) compared to other chemotherapy regimen at primary and updated analyses. The incidence of grade 3-5 AEs, infusion-related reactions (IRRs), and infection were higher in the obinutuzumab based chemotherapy group compared to other chemotherapies. The economic researches conducted in China, United States, Japan, Italy and Norway had demonstrated that obinutuzumab-based chemothrepy was cost-effective compared to other chemothrepies. Although obinutuzumab significantly prolonged PFS and was cost-effective, its safety profile was considered lower.Conclusion Compared with other chemothrapy regimen, obinutuzumab based chemotherapy significantly prolonged PFS and was cost-effective, while its safety profile was considered lower. Therefore, medical professionals should be caution when using or introducing obinutuzumab treatment for FL patients.

Introduction: Vedolizumab is a gut-selective anti-lymphocyte trafficking biologic indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD) in Canada. Objective: The objective of this study was to evaluate the cost effectiveness of treatment sequencing for UC and CD from a public healthcare payer perspective, leveraging new real-world evidence from the literature and the EVOLVE study, a retrospective chart review. Methods: Using separate decision tree/Markov models to assess cost effectiveness for UC and CD, two sequencing approaches were estimated for adult patients (≥ 18 years) diagnosed with UC or CD who were biologic-naïve: vedolizumab as first-line biologic followed by anti-tumor necrosis factor (TNF)-α versus first-line anti-TNFα followed by vedolizumab. Treatment effectiveness (response and remission), surgery rates, dose escalation and regain of response and safety inputs were estimated from EVOLVE, a retrospective chart review of real-world data, and evidence synthesis from the literature, whereas costs and utilities were estimated from health technology assessment reports, clinical trials, and the literature. Biosimilar costs were used for anti-TNFα. Both models simulated a 5-year time horizon and discounted costs and outcomes at 1.5%. Probabilistic base-case analyses (n = 10,000) reported total costs (2023 Canadian dollars) and quality-adjusted life-years (QALYs). Several scenario analyses were conducted to explore robustness of results. Results: In UC, vedolizumab as a first-line biologic followed by anti-TNFα resulted in an incremental gain of 0.09 QALYs (2.46 vs. 2.55) and saved $7179 ($134,028 vs. $126,848), making this a dominant strategy compared with first-line anti-TNFα followed by vedolizumab. In CD, use of vedolizumab as a first-line biologic resulted in an incremental gain of 0.04 QALYs (3.35 vs. 3.39) at an incremental cost of $50,631 ($89,850 vs. $140,381) versus first-line anti-TNFα followed by vedolizumab (incremental cost-effectiveness ratio of $1,265,775 per QALY). Conclusions: Based on this analysis, sequencing vedolizumab as a first-line biologic prior to anti-TNFα in UC and CD provided additional clinical benefit to patients. In UC, vedolizumab as a first-line biologic also saved healthcare system costs compared with anti-TNFα, whereas in CD, vedolizumab provided incremental benefit at an incremental cost, which was not considered cost effective at a threshold of $50,000/QALY.

Background and objectives: Disorders of gut-brain interaction are highly prevalent and burdensome conditions for both patients and healthcare systems. Given the limited effectiveness of pharmacotherapy in treating disorders of gut-brain interaction, non-pharmacological interventions are increasingly used; however, the value for money of non-pharmacological treatments is uncertain. This is the first review to assess the economic evaluation evidence of non-pharmacological interventions for disorders of gut-brain interaction. Methods: A scoping review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Reporting adhered to ISPOR's good practices for systematic reviews with cost and cost-effectiveness outcomes. Comprehensive searches were performed on 24 October, 2023, and an updated search was run on 18 May, 2024 in PubMed/MEDLINE, Embase, Web of Science, Scopus and the International HTA database, with two reviewers screening studies in parallel. The novel Criteria for Health Economic Quality Evaluation (CHEQUE) framework was used to assess methodological and reporting quality. Reporting quality was further assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022. Results: Fifteen studies were included. Most studies examined treatments for irritable bowel syndrome. Cognitive behavioural therapy, dietary interventions and sacral neuromodulation were cost effective. Acupuncture and physiotherapy were not. CHEQUE assessment showed 12 studies met at least 70% of the methodological criteria, and 14 studies achieved 70% or more for reporting quality. Conclusions: This review highlights gaps in the current evidence base, particularly in the robustness and generalisability of results due to methodological inconsistencies. Future research should incorporate longer follow-ups, comprehensive cost assessments, subgroup analyses, equity considerations and clearer justifications for modelling assumptions.

Background and objective: This systematic literature review addresses model-based cost-effectiveness studies for therapy response monitoring with positron emission tomography (PET) generally combined with low-dose computed tomography (CT) for various cancer types. Given the known heterogeneity in therapy response events, studies should consider patient-level modelling rather than cohort-based modelling because of its flexibility in handling these events and the time to events. This review aims to identify the modelling methods used and includes a systematic assessment of the assumptions made in the current literature. Methods: This study was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Information sources included electronic bibliographic databases, reference lists of review articles and contact with experts in the fields of nuclear medicine, health technology assessment and health economics. Eligibility criteria included peer-reviewed scientific publications and published grey literature. Literature searches, screening and critical appraisal were conducted by two reviewers independently. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) were used to assess the methodological quality. The Bias in Economic Evaluation (ECOBIAS) checklist was used to determine the risk of bias in the included publications. Results: The search results included 2959 publications. The number of publications included for data extraction and synthesis was ten, representing eight unique studies. These studies addressed patients with lymphoma, advanced head and neck cancers, brain tumours, non-small cell lung cancer and cervical cancer. All studies addressed response to chemotherapy. No study evaluated response to immunotherapy. Most studies positioned PET/CT as an add-on modality and one study positioned PET/CT as a replacement for conventional imaging (X-ray and contrast-enhanced CT). Three studies reported decision-tree structures, four studies reported cohort-level state-transition models and one study reported a partitioned survival model. No patient-level models were reported. The simulation horizons adopted ranged from 1 year to lifetime. Most studies reported a probabilistic analysis, whereas two studies reported a deterministic analysis only. Two studies conducted a value of information analysis. Multiple studies did not adequately discuss model-specific aspects of bias. Most importantly and regularly observed were a high risk of structural assumptions bias, limited simulation horizon bias and wrong model bias. Conclusions: Model-based cost-effectiveness analysis for therapy response monitoring with PET/CT was based on cohorts of patients instead of individual patients in the current literature. Therefore, the heterogeneity in therapy response events was commonly not addressed appropriately. Further research should include more advanced and patient-level modelling approaches to accurately represent the complex context of clinical practice and, therefore, to be meaningful to support decision making. Registration: This review is registered in PROSPERO, the international prospective register of systematic reviews funded by the National Institute for Health Research, with CRD42023402581.

Background: Adults with learning disabilities face increased risks of unhealthy lifestyle behaviours, including alcohol consumption, smoking, low physical activity, sedentary behaviour and poor diet. Lifestyle modification interventions that target health-risk behaviours can prevent or reduce their negative effects. The goal of this project was to investigate the effectiveness and underlying mechanisms of lifestyle modification interventions in adults with learning disabilities. Methods: A systematic review and meta-analysis were conducted to determine the effectiveness of lifestyle modification interventions and their components in targeting health risk behaviours in adults with learning disabilities. Major electronic databases, clinical trial registries, grey literature, and citations of systematic reviews and included studies were searched in January 2021 (updated in February 2022). We included randomised and non-randomised controlled trials targeting alcohol consumption, smoking, low physical activity only, sedentary behaviour and poor diet in adults (aged ≥ 18 years) with learning disabilities. Studies were also coded based on the extent of use of theories and behaviour change techniques in interventions. Risk of bias in studies was assessed using appropriate tools. A realist synthesis of qualitative, quantitative and mixed-methods literature was conducted to complement the systematic review findings by identifying key intervention mechanisms that are likely to improve the health of adults with learning disabilities. Data were synthesised in the form of a programme theory regarding complex causal mechanisms and how these interact with social context to produce outcomes. All findings were integrated into a logic model. A patient and public involvement group provided input and insights throughout the project. Results: A total of 80 studies with 4805 participants were included in the systematic review. The complexity of lifestyle modification interventions was dismantled by identifying six core components that influenced outcomes. These components could be present in interventions targeting single or multiple health risk behaviors, either as individual elements or in various combinations. Interventions on alcohol and smoking behaviours were found to be effective, but this was based on limited evidence. The effectiveness of interventions targeting low physical activity only or multiple behaviours (low physical activity only, sedentary behaviours and poor diet) was mixed. All interventions had a varying level of statistical significance. The intervention-level network meta-analysis for weight management outcomes showed none of the interventions was associated with a statistically significant change in outcomes when compared to treatment as usual and each other. Similar findings were observed in the component network meta-analysis. A variety of theories and behaviour change techniques were employed in the development and adaptation of interventions. Most studies had a high and moderate risk of bias. A total of 79 studies, reporting the experiences of more than 3604 adults with intellectual disabilities and over 490 caregivers, were included in the realist synthesis. The resulting programme theory highlighted the contexts and mechanisms relating to support involvement, negotiating the balance between autonomy and behaviour change, fostering social connectedness and fun, the accessibility and suitability of intervention strategies and delivery, along with the broader behavioural pathways to lifestyle change. It also brought out the importance of working with people with lived experiences when developing and evaluating interventions. Our logic model, bringing together the findings of both syntheses, provides guidance on the design of future interventions. Discussion: This study was the first comprehensive mixed-methods evidence synthesis to explore lifestyle modification interventions targeting multiple unhealthy lifestyle behaviours in adults with learning disabilities. We conclude that future research could benefit from codeveloping interventions and population-specific assessment frameworks with people with lived experiences. There is a need for more high-quality research with appropriate outcomes and a focus on qualitative and mixed-methods research to better understand what works for whom and why. Trial registration: This trial is registered as PROSPERO CRD 42020223290. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR128755) and is published in full in Health Technology Assessment; Vol. 29, No. 4. See the NIHR Funding and Awards website for further award information.

Spinal muscular atrophy (SMA) is a rare inherited autosomal recessive progressive disease of a varying phenotype, with varying clinical symptoms, and as a result the patients suffering from it require multiple types of care. It was deemed useful to conduct a systematic literature review on the pharmacoeconomic evaluations of all currently registered disease-modifying therapies in order to inform policy and highlight research gaps. Pharmacoeconomic analyses written in English and published after 2016 were considered for inclusion. PubMed/Medline, Global Health and Embase were systematically and separately searched between 16 October and 23 October 2023. Hand-searching was also conducted on PubMed based on reference lists of published literature. After the exclusion criteria were applied, 14 studies were included. BMJ checklist was used for quality assessment and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to assess the quality of reporting of all included studies. Data extraction was performed manually. Regarding evidence synthesis, data were heterogeneous and are thus presented based on comparison. This study confirms the need for pharmacoeconomic analyses (cost-effectiveness or cost-utility) also in cases when the cost of treatment is very high and the incremental cost-effectiveness ratio values exceed the usual, acceptable values for standard therapy. Specific willingness to pay thresholds for orphan medicines are of the utmost importance, to allow patients with SMA to have access to safe and effective treatments. With such economic evaluations, it is possible to compare the value of medications with the same indication, but it should be emphasized that in the interpretation of data and in making decisions about the use of medicines, the impact of new knowledge should be considered.

Introduction: This systematic review aims to explore the existing evidence on the cost-effectiveness of brexu-cel across different international jurisdictions. Methods: A systematic search of articles on Embase, Medline, Econlit, Web of Science, Scopus, gray literature, and a manual search of HTA reports was done until 24 June 2024. Original English articles and reports from different countries assessing the cost-effectiveness of brexu-cel in relapsed/refractory acute lymphoblastic leukemia (R/R ALL) and mantle cell lymphoma (R/R MCL) were included. This review was registered in the Open Science Framework (OSF) registry. Results: Of the 149 records, 22 articles underwent full-text review after the title and abstract screening, five met the inclusion criteria along with seven HTA reports from Australia, Canada, Scotland, and England. The CEA studies were from the US, England, Canada, and Italy, with varying perspectives, mainly adopting a partitioned survival model and lifetime horizons. The model input data from the ZUMA-2 and ZUMA-3 trials were used for brexu-cel, with comparisons from their respective trials or literature. Conclusion: Brexu-cel was found cost-effective in all the CEA studies and an HTA report from Scotland, but the other HTA agencies reported uncertainties around the cost-effectiveness of brexu-cel for R/R ALL and R/R MCL. Registration: Open Science Framework. (Reg doi: https://doi.org/10.17605/OSF.IO/JZU6Y).

Background: Many people infected with the Mycobacterium tuberculosis complex (the bacteria that cause tuberculosis [TB]) have an inactive stage of infection known as latent tuberculosis infection (LTBI). A person with LTBI is at risk of developing active TB. Screening for, and treating people with, LTBI is an important part of preventing adverse health outcomes, reducing the risk of reactivation and the further spread of tuberculosis in a community. We conducted a health technology assessment of interferon-gamma release assay (IGRA) for the detection of LTBI, compared to the standard tuberculin skin test (TST) to evaluate the diagnostic accuracy, cost-effectiveness, the budget impact of publicly funding, and health care provider preferences and values. Methods: We performed a systematic literature search of the clinical evidence as an overview of systematic reviews. We reported the findings of the identified reviews, including their quality assessment of the body of evidence. We performed a systematic literature search of the economic evidence and included published Canadian cost-effectiveness studies. We assessed the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We developed a probabilistic decision-tree model to estimate the incremental costs of IGRA strategies versus TST alone over 1 year in eligible population subgroups. IGRA was examined as a single test and in a sequential pathway with tuberculin skin test (TST; the test order depended on the type of population). We considered subpopulations at high risk of LTBI for whom IGRA would be preferred, as indicated by the Canadian TB Standards published in 2022 (hereinafter, the Standards); e.g., people who received a Bacille Calmette-Guérin (BCG) vaccine, such as BCG-vaccinated immigrants and people identified in contact investigations. We also considered people with comorbid conditions or who were undergoing treatments that may cause low immune function and, hence, may test incorrectly negative. We estimated the total 5-year budget impact (in 2024 CAD) for publicly funding IGRA testing in Ontario. To contextualize the potential value of IGRA, we spoke with health care providers about people requiring TB testing for LTBI. We attempted to reach out to people who had experience with IGRA or TST but did not receive any feedback. Results: We included 12 systematic reviews that included over 500 unique primary studies in the clinical evidence overview of reviews and found good evidence aligned with the uses of IGRA outlined in the Standards. This overview of reviews summarizes the existing evidence on diagnostic accuracy and the clinical utility of IGRA for LTBI. Interferon-gamma release assay was found to have good evidence as a rule-in test for LTBI due to consistently high specificity. The reviews reported slightly lower sensitivity among people who have underlying immunosuppression conditions (e.g., people who are HIV positive or have received an organ transplant, or are on cancer treatment or dialysis) compared to a more general population. However, compared to TST (the standard test for TB), IGRA appears to have fewer false-positive results, as signaled by a lower risk difference of developing active TB among those who tested positive on both LTBI tests in head-to-head comparisons. This was particularly notable in immunocompromised populations and was also observed in children and the elderly (e.g., people in nursing homes) and those who have received an anti-tuberculin vaccination known as the BCG vaccine.Additionally, IGRA may be informative for people with immunocompromising conditions who are at risk of a false-negative result from a TST, as it yields indeterminate findings, signaling that further clinical investigation may be needed.We included 5 economic studies from Canada (using a public payer perspective), which found that IGRA, either as a sequential test following TST or as a standalone test, was cost-effective or cost-saving compared with TST alone for LTBI in high-risk populations as identified in the Standards. All reviewed studies were of good quality and 3 studies were directly applicable to the Ontario context (GRADE: High). Therefore, we did not conduct a primary economic evaluation for Ontario.Our reference case budget impact analysis showed that publicly funding IGRA in Ontario in all examined subpopulations over the next 5 years was associated with additional costs ranging from $2.99 million (IGRA alone) to $18.80 million (IGRA in sequential pathways with TST). These overall estimates include potential savings in some subpopulations and additional costs in others. In the population-specific analyses, we estimated cost savings of $1.63 million or higher over 5 years with publicly funded IGRA testing in BCG-vaccinated immigrants or BCG-vaccinated people identified via contact investigations (who are susceptible to a false positive result with the TST alone). These cost-savings resulted from reductions in costs of follow-up evaluation and treatment (due to prevention of reactivated LTBI). We found additional costs of about $6.26 million or higher over 5 years with publicly funded IGRA testing in immunocompromised people due to increased appropriate medical evaluations for those who were previously incorrectly identified as negative. In sensitivity analyses, if we assumed a high chance of reactivation of LTBI into active TB in immunocompromised populations, then IGRA testing resulted in cost savings.Health care providers who we surveyed had positive comments about IGRA, and expressed it as patients' preferred test for LTBI, partly because this test requires only 1 office visit (compared to the multiple visits needed for TST), thus reducing the effect of barriers such as transportation, language, childcare and employment arrangements. Conclusions: Interferon-gamma release assay testing was found to have good diagnostic accuracy and to be cost-effective or cost-saving for LTBI in populations aligned with the recommended uses of the Standards. We estimate that publicly funding IGRA in Ontario for all examined population subgroups would result in additional costs of between $2.99 million and $18.80 million over 5 years, depending on how the test is used. In the population-specific analyses, we estimate a cost savings of $1.63 million or higher with IGRA testing in eligible BCG-vaccinated immigrant populations or BCG-vaccinated people identified via contact investigations. There was a preference for IGRA among health care practitioners, particularly to support people who may have challenges with the available alternative tests (e.g., TST).

Background: 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. Objective: To investigate the efficacy and safety of anti-vascular endothelial growth factor therapy for the treatment of diabetic retinopathy when compared to panretinal photocoagulation. Methods: 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. Results: 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. Conclusions: 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. Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR132948.

Background: The assessment of technology in hospital settings is a crucial step towards ensuring the delivery of efficient, effective, and safe healthcare. Objective: This study conducts a Hospital-Based Health Technology Assessment to evaluate the efficacy of a screening rapid test for mild Traumatic Brain Injury (mild TBI) utilizing blood biomarkers, specifically Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-terminal Hydrolase L1 (UCH-L1). The assessment focuses on the clinical utility and performance characteristics of the proposed rapid test within a hospital setting. Methods: The screening model was meticulously examined for its ability to accurately detect mild TBI, considering the sensitivity and specificity of GFAP and UCH-L1 as blood biomarkers. The study involved a thorough evaluation of the test's diagnostic accuracy, comparing its outcomes with established standards for mild TBI diagnosis.Results from the Hospital-Based Health Technology Assessment highlight the potential of the GFAP and UCH-L1 blood biomarker-based rapid test as an efficient screening tool for mild TBI within a hospital environment. The evidence results show that the test is highly sensitive (91 percent to 100 percent) for the prediction of acute traumatic intracranial lesions, which helps rule out injury when the result is negative. When used within 12 hours of injury in adult patients with mild TBI, this test holds promise in reducing the utilization of CT. Conclusion: The findings contribute valuable insights into the feasibility and reliability of implementing this technology for timely and accurate identification of mild TBI, enhancing clinical decision making and patient care in hospital settings.

Background The assessment of technology in hospital settings is a crucial step towards ensuring the delivery of efficient, effective, and safe healthcare.Objective This study conducts a Hospital-Based Health Technology Assessment to evaluate the efficacy of a screening rapid test for mild Traumatic Brain Injury (mild TBI) utilizing blood biomarkers, specifically Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-terminal Hydrolase L1 (UCH-L1). The assessment focuses on the clinical utility and performance characteristics of the proposed rapid test within a hospital setting.Methods The screening model was meticulously examined for its ability to accurately detect mild TBI, considering the sensitivity and specificity of GFAP and UCH-L1 as blood biomarkers. The study involved a thorough evaluation of the test's diagnostic accuracy, comparing its outcomes with established standards for mild TBI diagnosis. Results from the Hospital-Based Health Technology Assessment highlight the potential of the GFAP and UCH-L1 blood biomarker-based rapid test as an efficient screening tool for mild TBI within a hospital environment. The evidence results show that the test is highly sensitive (91 percent to 100 percent) for the prediction of acute traumatic intracranial lesions, which helps rule out injury when the result is negative. When used within 12 hours of injury in adult patients with mild TBI, this test holds promise in reducing the utilization of CT.Methods The screening model was meticulously examined for its ability to accurately detect mild TBI, considering the sensitivity and specificity of GFAP and UCH-L1 as blood biomarkers. The study involved a thorough evaluation of the test's diagnostic accuracy, comparing its outcomes with established standards for mild TBI diagnosis. Results from the Hospital-Based Health Technology Assessment highlight the potential of the GFAP and UCH-L1 blood biomarker-based rapid test as an efficient screening tool for mild TBI within a hospital environment. The evidence results show that the test is highly sensitive (91 percent to 100 percent) for the prediction of acute traumatic intracranial lesions, which helps rule out injury when the result is negative. When used within 12 hours of injury in adult patients with mild TBI, this test holds promise in reducing the utilization of CT.Conclusion The findings contribute valuable insights into the feasibility and reliability of implementing this technology for timely and accurate identification of mild TBI, enhancing clinical decision making and patient care in hospital settings.

Background: The cost-effectiveness of interventions is a key issue owing to the limited resources of healthcare services. Objective: To conduct a systematic review of economic evaluations of technology-based healthcare interventions in care support for people with dementia or mild cognitive impairment (MCI) and their caregivers, and of the tools used to assess effectiveness and costs. Methods: The following databases were used: PubMed, National Health Service Economic Evaluation Database, and Health Technology Assessment. A total of 207 articles from 2012 to 2024 were identified and then screened. Results: Seventeen studies were included, of which nine were study protocols. Almost half (n = 8) the interventions were multicomponent. The most common components used in the interventions were cognitive stimulation, physical functioning and continuing support. Regarding the efficiency results of these interventions, only three studies provided a full economic evaluation. The most frequent tools in the economic evaluations used to measure effectiveness (measured in quality-adjusted life years) and costs were the European Quality of Life-5 Dimensions and Resource Utilization in Dementia instruments, respectively. Conclusions: Most of the interventions evaluated were cost-effective. However, these results should be interpreted with caution, given the scarcity of the literature, and further economic evaluations of technology-based healthcare interventions for people with mild dementia or MCI care support and their caregivers are therefore needed. Additionally, a meta-analysis could not be performed due to the heterogeneity of the data.