Purpose: Mobile health (mHealth) applications (apps) have emerged as powerful tools for enhancing clinical decision-making, knowledge dissemination, and proactive care in traumatic dental injuries (TDIs). This systematic review aims to collate and assess the available evidence on the usefulness of mobile apps in (1) diagnosis, (2) prevention, (3) management, and (4) education of TDIs. Methods: This review examined studies published between January 2012 and August 2024, focusing on randomised controlled trials (RCTs), clinical trials, cohort studies, and cross-sectional studies that assessed the effectiveness of mobile health apps in the management of TDI care. Study quality was assessed using the Cochrane Risk of Bias Tool 2.0 for RCTs and the modified Newcastle-Ottawa Scale for cross-sectional studies. The GRADE approach was used to assess the certainty of the evidence. Results: Sixteen studies met the inclusion criteria, including 12 cross-sectional studies and 4 RCTs. The cross-sectional studies primarily assessed knowledge improvement, while the RCTs focused on skill development and practical applications. Quality assessments indicated notable methodological concerns. All four RCTs were rated as high risk of bias due to inadequate randomisation, lack of blinding, and participant attrition. According to the GRADE approach, the overall certainty of the evidence was judged to be very low. Conclusion: While mobile health applications such as ToothSOS, Dental Trauma, and Injured Tooth show promise in improving knowledge and decision-making related to TDIs, the evidence is limited by high risk of bias and low quality. Future studies should focus on rigorous RCTs and explore AI integration to enhance effectiveness.

Background: The global push to scale up telemedicine services is challenged by complex, multilevel, multifaceted implementation and a lack of consensus on what the evidence-based essential building blocks of implementation are. Objective: We aimed to evaluate the evidence base supporting telemedicine implementation knowledge tools; identify shared conceptual constructs and outliers; and formulate recommendations to guide the design, development, and optimization of telemedicine services. Methods: We conducted implementation research using a rapid umbrella review, that is, an overview of systematic reviews, in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). In total, we searched 3 databases (PubMed, Web of Science, and Scopus) for studies focusing on telemedicine implementation frameworks, models, and tools, collectively referred to as "knowledge tools." Reviews meeting the operational definition of a systematically undertaken, secondary evidence synthesis, such as systematic and scoping reviews, and those published from January 2018 to May 2024 were considered. A meta-aggregative qualitative analysis was undertaken, comprising inductive thematic synthesis. Results: In total, 18 reviews were selected, encompassing 973 primary studies. Global perspectives were reflected in 61% (n=11) of the reviews, while 33% (n=6) focused on low- and middle-income country contexts. The primary research included in the reviews represented 63 countries, spanning the Americas, Europe, Africa, the Middle East, and Asia and the Pacific. Findings indicated substantial heterogeneity across the identified telemedicine implementation theories, models, and frameworks. However, following evidence synthesis, considerable convergence was observed, highlighting a state-of-the-art understanding of the essential requirements for a national telemedicine implementation ecosystem. These were categorized into "process" and "thematic" dimensions. Process dimensions included readiness and needs assessment, road map and planning, managing change, implementing telemedicine services, and continuous improvement and measuring performance. Thematic dimensions covered human and sociocultural aspects; organization, operations, management, and leadership; communication and coordination; policy, legal, and financial considerations; clinical health condition and quality of care; and the wider context. Conclusions: The findings of this study inform a pressing translational research knowledge gap in telemedicine implementation, hindering the implementation of high-quality, sustainable, and scalable telemedicine systems. The study contributes to building global consensus on the state of the art of key constructs in telemedicine implementation and recommends that future research focus on field-testing the evidence-based implementation tools to evaluate their usability and adaptability across diverse telemedicine contexts.

Background: Electrophysiology (EP) procedures, including cardiac implantable electronic devices (CIEDs) and ablations, are widely used to manage arrhythmias and heart failure. These interventions, though effective, require substantial resources, prompting the need for systematic economic evaluations to inform healthcare decision-making. Methods: A systematic review of studies from 2007 to 2024 was conducted in two phases. Phase one assessed trends in economic evaluations of EP procedures, analyzing 129 studies across regions and timeframes. Phase two focused on cost-effectiveness analyses of implantable cardioverter defibrillators (ICDs), cardiac resynchronization therapy defibrillators (CRT-Ds), and atrial fibrillation (AF) ablation, examining outcomes like quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs), while identifying factors influencing economic results. Results: EP procedures generally demonstrated favorable cost-effectiveness, particularly in high-income regions. Studies on ICDs and CRT-Ds consistently supported their economic value for patients with arrhythmias or heart failure, while AF ablation showed potential for long-term benefits, particularly when compared to medical therapies. However, results varied by region, reflecting differences in healthcare systems, costs, and patient populations. Conclusions: The review highlights the overall cost-effectiveness of EP procedures in many settings but underscores the need for tailored economic evaluations in low- and middle-income countries. Simplified methodologies and greater attention to regional contexts are recommended to guide resource allocation and policy development globally.

Background: Sickle cell disease (SCD) and Diamond-Blackfan anemia syndrome (DBAS) are two hereditary blood diseases that present significant challenges to patients, their caregivers, and the healthcare system. Both conditions cause severe health complications and have limited treatment options, leaving many individuals without access to curative therapies like hematopoietic stem cell transplantation. Recent advancements in gene and cell therapies offer the potential for a new curative option, marking a pivotal shift in the management of these debilitating diseases. However, the implementation of these therapies necessitates a nuanced understanding of the ethical and social implications. Methods: In this mixed methods systematic review, we explore the responsible development and implementation of gene and cell therapies for SCD and DBAS and aim to sketch a path toward ethically and socially sound implementation. Drawing upon principles of Responsible Research & Innovation and the 4A framework of availability, accessibility, acceptability, and affordability, we thematically analyze existing research to illuminate the ethical and social dimensions of these therapies. Following established PRISMA and JBI Manual guidelines, a search across multiple databases yielded 51 peer-reviewed studies with publication dates ranging from 1991 to 2023. Results: Our thematic analysis shows that the theme of acceptability is heavily shaped by interactions between patients, caregivers, healthcare professionals and researchers, influencing treatment decisions and shaping the development of curative gene and cell therapies. Despite the generally positive perspective on these therapies, factors like the limited treatment options, financial constraints, healthcare professional attitudes, and (historical) mistrust can impede stakeholder decision-making. While acceptability focuses on individual decisions, the themes of availability, accessibility, and affordability are interconnected and primarily driven by healthcare systems, where high research and development costs, commercialization and a lack of transparency challenge equitable access to these therapies. This diminishes the acceptability for patients, revealing a complex interdependence of the themes. Conclusions: The findings suggest the need for improved communication strategies in clinical practice to facilitate informed decision-making for patients and caregivers. Policy development should focus on addressing pricing disparities and promoting international collaboration to ensure equitable access to therapies. This review has been pre-registered in PROSPERO under registration number CRD42023474305.

Background: White light (conventional) colonoscopy (WLC) is widely used for colorectal cancer screening, diagnosis and surveillance but endoscopists may fail to detect adenomas. Our goal was to assess and synthesize overall and subgroup-specific adenoma miss rates (AMR) of WLC in daily practice. Methods: We conducted a systematic review in MEDLINE, EMBASE, Cochrane Library, and grey literature on studies evaluating diagnostic WLC accuracy in tandem studies with novel-colonoscopic technologies (NCT) in subjects undergoing screening, diagnostic or surveillance colonoscopy. Information on study design, AMR overall and specific for adenoma size, histology, location, morphology and further outcomes were extracted and reported in standardized evidence tables. Study quality was assessed using the QUADAS-2 tool. Random-effects meta-analyses and meta-regression were performed to estimate pooled estimates for AMR with 95% confidence intervals (95% CI) and to explain heterogeneity. Results: Out of 5,963 identified studies, we included sixteen studies with 4,101 individuals in our meta-analysis. One in three adenomas (34%; 95% CI: 30-38%) was missed by WLC in daily practice individuals. Subgroup analyses showed significant AMR differences by size (36%, adenomas 1-5 mm; 27%, adenomas 6-9 mm; 12%, adenomas ≥ 10 mm), histology (non-advanced: 42%, advanced: 21%), morphology (flat: 50%, polypoid: 27%), but not by location (distal: 36%, proximal: 36%). Conclusions: Based on our meta-analysis, one in three adenomas could be missed by WLC. This may significantly contribute to interval cancers. Our results should be considered in health technology assessment when interpreting sensitivity of fecal occult blood or other screening tests derived from studies using WLC as "gold standard".

Background: Population-wide newborn blood spot screening programmes are a successful public health intervention used to detect whether the baby is at risk of certain rare conditions, with the aim of earlier diagnosis and provision of optimal care and treatment. Evaluating candidate conditions to include in newborn blood spot and genetic sequencing raises questions regarding acceptability to parents/carers. Methods: In the context of the possible expansion of the newborn blood spot screening programme in the United Kingdom, this review aimed to systematically review research on the acceptability to parents of newborn blood spot screening and genetic sequencing. A protocol was developed prior to commencing the review and was registered on the PROSPERO database. A team of researchers carried out the review, with checking at all stages carried out by at least two individuals. We included research published after 2013 with participants who were pregnant or a recent parent of a newborn and were resident in a high-income country. We included quantitative and qualitative studies that investigated the acceptability to parents/carers of newborn blood spot screening or genetic sequencing. Quantitative studies were narratively synthesised, and theories/frameworks identified and evaluated. Qualitative studies were analysed for recurring themes, and a meta-synthesis was carried out to compare and contrast these two types of data. We quality appraised included articles using tools appropriate for their study design. Results: Searches were carried out in September to November 2023 and screening identified 25 relevant research articles. Just over half were from North America, with four existing reviews and nine qualitative studies. Domains of acceptability described in the literature were: support for screening; level of anxiety, information and knowledge; consent; views of the procedure; and support after screening. The research indicated consensus support for blood spot screening, and for expanding to some other conditions, although some parental anxiety was reported. Parents/carers mostly perceived that they had received sufficient information, but the timing of this could be improved. While parents indicated interest in genomic screening, studies highlighted the need for clearer consent procedures and greater support for parents following genomic screening than for blood spot screening. Only three included studies reported using any kind of theoretical framework. Discussion: Most parents/carers found newborn blood spot screening programmes to be acceptable and favoured their large-scale implementation. A minority of parents/carers expressed concerns regarding the acceptability of processes underpinning newborn blood spot screening, such as consent, the timing of receiving information and support available after testing. More research is needed regarding the acceptability of newborn genomic sequencing screening programmes, which are less established compared with newborn blood spot screening programmes. Limitations: The over-representation of studies conducted in the United States has implications for the applicability of findings to other countries where testing is not typically mandatory and health systems differ considerably. Most studies were of cross-sectional design and there was limited representation of people from lower incomes and non-white ethnicity. While the inclusion of studies only in populations of future or very recent parents provided coherence to the findings, unclear reporting of participants may have resulted in under- or overinclusion of some studies. Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR159927.

Introduction: There is no recent consensus on the effectiveness of teledentistry versus in-person examination in the diagnosis of dental caries, especially after the COVID-19 pandemic. Objective: To assess the diagnostic accuracy of teledentistry versus in-person examination for dental caries diagnosis (PROSPERO #CRD42023410962). Methods: This systematic review and meta-analysis compared the effectiveness of teledentistry versus in-person examination for dental caries diagnosis. The eligibility criteria were peer-reviewed studies published in English between January 2013 and December 2021 that reported diagnostic parameters (specificity and sensitivity) for caries detection in primary and permanent dentition. Articles were extracted using search strategies from PubMed and CINAHL databases and screened using PRISMA-DTA guidelines, following a review for quality assessment and risk of bias using the QUADAS-2 and JBI Critical Appraisal Checklists. Meta-analysis was conducted in R using the MADA package. A descriptive analysis of the sensitivity, specificity, diagnostic odds ratio, and confidence intervals was performed with respective forest plots. Heterogeneity was assessed using Cochrane and Higgins's 2 tests. Univariate measures of diagnostic accuracy were performed based on the DerSimonian-Laird random effect and reported summary diagnostic odds ratios. Results: Twelve studies met the inclusion criteria and were reviewed and included in the meta-analysis. The diagnostic parameters ranged from 45.6% to 88.3% for sensitivity, 55.2% to 98.3% for specificity, 79% to 92% for positive predictive value, 48% to 97% for negative predictive value, and 70% to 96% for accuracy. The κ scores ranged from 0.46 to 0.89 for teledentistry modalities. Tests for equality of sensitivities and specificities were significant ( < 0.001). The studies were not heterogeneous with Cochran's : 14.502 ( = 0.206) and Higgins's 2 of 24%. The multivariable analysis showed a diagnostic odds ratio based on the DerSimonian-Laird random effect of 35.14, which indicates that the odds of caries detection via teledentistry is 35 times more true positive (i.e., correctly identifying a positive condition) than false positive. Conclusions: Diagnosis of caries via teledentistry is effective and comparable to in-person diagnosis. Remote assessments are consistent in diagnostic accuracy for caries.Knowledge Transfer Statement:This systematic review and meta-analysis added to the evidence about using teledentistry assessment as a diagnostically accurate tool to detect dental caries. Using teledentistry dental practices could promote greater access to dental and oral health care in the absence of in-person assessment.

Hysterectomy, removal of the uterus, is a commonly performed surgery for gynaecological morbidities. Emerging evidence indicates that hysterectomy performed before age 45 (early hysterectomy), is associated with considerable risks to women's health. While most evidence on hysterectomy is from high-income settings, national surveys from India report high prevalence of early hysterectomy in specific regions, as well as higher prevalence amongst women in rural areas and with less education. The median age at hysterectomy in India is close to ten years before the onset of natural menopause. India has recently introduced national guidelines to address early hysterectomy, but large evidence gaps on the causes and consequences remain - which in turn limits the potential effectiveness of interventions at the clinical, health system and community level. Methods: SAHELI is a Team Science study that will examine: (i) individual, social and health system determinants of early hysterectomy; (ii) women's treatment pathways to hysterectomy and for gynaecological morbidity in general; and (iii) the consequences of undergoing hysterectomy on women's physical, mental, economic and social well-being across the life course. This mixed-methods study includes population surveys amongst women in ages 25-49 in three high-prevalence states; qualitative health systems research to trace treatment journeys with women, health care providers and other stakeholders; evidence syntheses; and knowledge translation activities to ensure findings inform co-produced strategies and interventions. The study is grounded in a feminist epidemiology approach, aiming to examine individual and structural causes of vulnerability and prioritising the views of women, particularly in knowledge translation. Conclusions: SAHELI, implemented by an all-women, multi-disciplinary team, is the first study in India to examine the causes and consequences of hysterectomy in a life course approach. We aim to influence interventions, policy and future research on women's health, particularly access to quality gynaecological care and comprehensive health services through the life course.

Purpose: To perform a scoping review of the literature investigating the use of telemedicine in retinoblastoma (RB) care, as well as its integration into broader health-care systems worldwide. Methods: A comprehensive search of academic databases, Medline and Embase, as well as public, web-based sources, was performed. Article references were also screened for inclusion within the review. Only English-language sources that presented evidence of dedicated frameworks incorporating telemedicine-based RB care were included. Results: The review identified 57 peer-reviewed studies, of which 19 were found potentially eligible for inclusion. Following exclusion criteria and a web-based search, 11 sources referencing 10 telemedicine frameworks, comprising four peer-reviewed articles, and seven publicly available initiatives, were included. Major themes leveraging telemedicine in RB care included knowledge exchange and capacity building, the establishment of direct partnerships incorporating teleconsultation, and the development of care coordination networks. Many telehealth platforms were effectively integrated into health-care systems; however, challenges included the absence of RB specific initiatives, the need for publicly available, measurable peer-reviewed outcomes and the complexities of multidimensional RB care. Conclusion: Tele-efforts have the potential to enhance delivery of RB care to remote, resource-limited communities. Future research should explore improved integration of policy-driven telemedicine within health-care systems, assess the economic feasibility of providing such care, and facilitate empirical evaluations, ultimately leading to increased sustainability, funding and investment of these models.

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.

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: Sputum-based diagnostic methods for pulmonary tuberculosis (PTB) are challenging for patients who cannot produce sputum. Non-sputum-based approaches, such as tongue swab (TS), can address this gap. This study conducts an early Health Technology Assessment (HTA) of TS for PTB diagnosis in Thailand. Methods: We conducted a landscape review, stakeholder consultation, early health economic modeling, and established a Target Product Profile (TPP). The landscape review included a comprehensive literature analysis to identify gaps and unmet needs in PTB diagnosis in Thailand. Stakeholder consultations gathered insights from TB experts to validate the information. An early health economic model evaluated the cost-effectiveness of two innovative strategies: tongue swab with Loop-Mediated Isothermal Amplification (LAMP) and tongue swab with real-time polymerase chain reaction (RTPCR). The TPP outlines three target levels to guide innovators in designing effective clinical studies. Findings: The landscape review identified the clinical workflow and reimbursement process of all PTB diagnostic tests in Thailand. The gap of tuberculosis management was around diagnosis and treatment. Stakeholders indicated that PTB detection remains inefficient due to issues such as low-test accuracy, costs, delays, drug-resistance testing, and the need for specialized laboratory techniques and personnel. TS RTPCR is the best-performing strategy, outperforming other strategies for the targeted population from the modelling analysis. Interpretation: TS may serve as a viable alternative worth further exploration and development. An ongoing collaboration between early HTA researchers and innovators has identified valuable information for innovation development. Funding: This work was supported by Thailand Science Research and Innovation (TSRI), Thailand, Grant Number FFB670043/0401 and Wellcome Trust grant, Grant Number 223800/Z/21/Z.

The Arctic region, characterised by its remote and geographically challenging environment, is home to predominantly Indigenous populations who experience significant healthcare disparities compared to urban counterparts. This paper synthesises evidence on the persistent challenges in delivering healthcare in the Arctic, including geographical remoteness, healthcare personnel shortages, and cultural and language barriers. Telehealth emerges as a crucial solution, offering a nuanced approach to overcoming physical and systemic barriers. We review current implementations of telehealth in the Arctic, highlighting successful adaptations to local cultural contexts and technological limitations. By integrating a patient-centred approach, infrastructure readiness, and relevant telehealth services, a holistic healthcare delivery model tailored for the Arctic environment is proposed. New type of technologies is also proposed to enhance remote care possibilities. This paper underscores the need for collaborative efforts in research, policy making, and healthcare provision to ensure the sustainability and effectiveness of health services in the Arctic, aiming to close the gap in health equity. Key references from seminal works and recent studies provide a foundation for the discussions and recommendations presented.

Background: Kidney transplantation is the preferred treatment for end-stage kidney disease (ESKD) in the United States, yet access and outcomes vary by insurance type, race, and socioeconomic status. This systematic review synthesizes U.S.-based evidence on how insurance coverage influences transplant waitlisting, access, and outcomes. AI-assisted analysis was used to quantify disparities and propose policy recommendations. Methods: A systematic review of MEDLINE, EMBASE, and the Cochrane Database (through November 2024) was conducted to identify studies on insurance-related disparities in U.S. kidney transplantation (PROSPERO: CRD42023484733). AI-assisted synthesis using o3-mini-high (2025) was employed to identify patterns and guide policy development. Results: Among 2,163 records, 14 studies met inclusion criteria. Patients with Medicare or Medicaid-particularly racial and ethnic minorities-had lower referral rates and higher transplant waitlist rejection compared to those with private insurance. Socioeconomic barriers such as low income and limited education further impaired access and worsened post-transplant outcomes. Publicly insured recipients had higher post-transplant mortality and graft failure rates. Loss of Medicare after 36 months was associated with reduced immunosuppressant adherence and increased rejection. Disparities were amplified by Medicaid expansion variability and inconsistent transplant center policies. AI-assisted analysis confirmed these disparities and generated policy proposals including standardized referral guidelines, lifelong immunosuppressant coverage, targeted financial aid, equity-linked incentives for transplant centers, and scalable digital health solutions. Conclusion: Insurance type, race, and socioeconomic status significantly influence kidney transplant access and outcomes. AI-assisted analysis identified structural inequities and informed targeted policy strategies to advance transplant equity and support broader healthcare reform.

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 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: 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: Chronic neuropathic pain is a major health problem that adversely affects people's physical and mental well-being, as well as their quality of life. Percutaneous peripheral nerve stimulation (PNS) may offer a minimally invasive option earlier in the treatment continuum for adults with chronic neuropathic pain that is refractory to conventional medical management. We conducted a health technology assessment of PNS for adults with chronic neuropathic pain, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding PNS, and patient preferences and values. Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Cochrane risk-of-bias tool for randomized controlled trials and the Risk of Bias in Non-randomized Studies - of Interventions for observational studies, and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted a cost-utility analysis with a 3-year horizon from a public payer perspective. We also analyzed the budget impact of publicly funding PNS in adults with chronic neuropathic pain in Ontario. To contextualize the potential value of PNS, we spoke to people with chronic pain, and to care partners of patients with chronic pain. Results: We included 17 publications (2 randomized controlled trials and 12 nonrandomized studies) in the clinical evidence review. These studies included chronic neuropathic pain in the trunk and the upper and lower extremities. Compared with placebo controls in adults with chronic neuropathic pain that is refractory to conventional medical management, permanent PNS likely decreases pain scores, likely improves functional outcomes, and likely improves health-related quality of life, but it has little to no effect on the use of pain medications (all GRADEs: Moderate). Compared with before implantation in adults with chronic neuropathic pain, permanent PNS may decrease pain scores, may decrease the use of pain medications, may improve functional outcomes, and may improve health-related quality of life (all GRADEs: Low). Compared with placebo controls in adults with chronic postamputation pain, temporary PNS may decrease pain scores, may decrease use of pain medications, may improve functional outcomes, and may improve health-related quality of life (all GRADEs: Low). Compared with before implantation in adults with chronic postamputation pain, temporary PNS may decrease pain scores, may decrease the use of pain medications, may improve functional outcomes, and may improve health-related quality of life (all GRADEs: Low). We did not find any studies that compared permanent PNS to temporary PNS. Implantation of a PNS system is a reasonably safe procedure; most adverse events were localized and mild in intensity (GRADEs: Moderate to Low).The incremental cost-effectiveness ratio of PNS in addition to standard care compared with standard care alone is $87,211 per quality-adjusted life-year (QALY) gained. The probability of PNS in addition to standard care being cost-effective versus standard care alone is 1.02% at a willingness-to-pay of $50,000 per QALY gained and 64.88% at a willingness-to-pay of $100,000 per QALY gained. The annual budget impact of publicly funding PNS in Ontario over the next 5 years ranges from an additional $0.97 million in year 1, increasing to $3.15 million in year 5, for a total of $10.09 million over 5 years. People with chronic pain and their family members and care partners viewed PNS favourably. Those who had direct experience with permanent PNS perceived it to be effective in reducing their pain levels, leading to a positive impact on their quality of life and mental health. Current barriers to accessing PNS include lack of awareness, cost, and geography. Conclusions: In adults with chronic neuropathic pain that is refractory to conventional medical management, permanent PNS likely improves pain outcomes, functional outcomes, and health-related quality of life but has little to no effect on the use of pain medications compared with placebo controls. Temporary PNS may improve pain outcomes, functional outcomes, and health-related quality of life, and it may reduce the use of pain medications. Implantation of a permanent or temporary PNS system is reasonably safe. The incremental cost-effectiveness ratio of PNS in addition to standard care compared with standard care alone is $87,211 per QALY gained. We estimate that publicly funding PNS in Ontario would result in additional costs of $10.09 million over the next 5 years. People who had direct experience with permanent PNS spoke of its effectiveness in reducing their pain levels and its positive impact on their quality of life and mental health. Barriers to accessing PNS include lack of awareness, cost, and geography.