What methods are currently available for incorporating implementation considerations within the economic evaluation of health technologies? A scoping review.

BACKGROUND: When clinically effective, cost-effective health interventions are not fully implemented in clinical practice, population health suffers. Economic factors are among the most commonly cited reasons for suboptimal implementation. Despite this, implementation and economic evaluation are not routinely performed in conjunction with one another. This review sought to identify and describe what methods are available for researchers to incorporate implementation within economic evaluation, how these methods differ, when they should be used, and where gaps remain. METHODS: We conducted a scoping review using systematic methods. A pearl-growing approach was used to identify studies. References and citations were identified using Web of Science and Scopus. We included for review any study that contained terms relating to economic evaluation and a series of implementation-related terms in the title or abstract. The search was conducted and validated using two independent researchers. RESULTS: Our review identified 42 unique studies that included a methodology for combining implementation and economic evaluation. The methods identified could be categorized into four broad themes: (i) policy cost-effectiveness approach (11 studies), (ii) value of information and value of implementation approach (16 studies), (iii) mixed methods approach (6 studies), and (iv) costing approach (9 studies). We identified a trend over time from methods that adopted the policy cost-effectiveness approach to methods that considered the trade-off between the value of information and value of implementation. More recently, mixed methods approaches to incorporate economic evaluation and implementation have been developed, alongside methods to define, measure and cost individual components of the implementation process for use in economic evaluation. CONCLUSION: Our review identified a range of methods currently available for researchers considering implementation alongside economic evaluation. There is no single method or tool that can incorporate all the relevant issues to fully incorporate implementation within an economic evaluation. Instead, there are a suite of tools available, each of which can be used to answer a specific question relating to implementation. Researchers, reimbursement agencies and national and local decision-makers need to consider how best to utilize these tools to improve implementation.

Economic evaluation of diagnosis and treatment for latent tuberculosis infection among contacts of pulmonary tuberculosis patients in Thailand.

Currently, interferon-gamma release assay (IGRA) is costly and not included as latent tuberculosis infection (LTBI) screening test strategy in Thailand's Universal Coverage Scheme (UCS) benefit package. The objective of this study was to assess the cost-utility of LTBI screening strategies among tuberculosis (TB) contacts in Thailand. A hybrid decision tree and Markov model was developed to compare the lifetime costs and health outcomes of tuberculin skin test (TST) and IGRA, in comparison to no screening, based on a societal perspective. Health outcomes were the total number of TB cases averted and quality-adjusted life years (QALYs), with results presented as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to explore uncertainties in all parameters. The ICER of TST compared with no screening was 27,645 baht per QALY gained, while that of IGRA compared to TST was 851,030 baht per QALY gained. In a cohort of 1000 TB contacts, both TST and IGRA strategies could avert 282 and 283 TB cases, respectively. At the Thai societal willingness-to-pay threshold of 160,000 baht per QALY gained, TST was deemed cost-effective, whereas IGRA would not be cost-effective, unless the cost of IGRA was reduced to 1,434 baht per test.

Bisoprolol in Patients With Chronic Obstructive Pulmonary Disease at High Risk of Exacerbation: The BICS Randomized Clinical Trial.

Importance: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Observational studies report that ß-blocker use may be associated with reduced risk of COPD exacerbations. However, a recent trial reported that metoprolol did not reduce COPD exacerbations and increased COPD exacerbations requiring hospital admission. Objective: To test whether bisoprolol decreased COPD exacerbations in people with COPD at high risk of exacerbations. Design, Setting, and Participants: The Bisoprolol in COPD Study (BICS) was a double-blind placebo-controlled randomized clinical trial conducted in 76 UK sites (45 primary care clinics and 31 secondary clinics). Patients with COPD who had at least moderate airflow obstruction on spirometry (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity <0.7; FEV1 <80% predicted) and at least 2 COPD exacerbations treated with oral corticosteroids, antibiotics, or both in the prior 12 months were enrolled from October 17, 2018, to May 31, 2022. Follow-up concluded on April 18, 2023. Interventions: Patients were randomly assigned to bisoprolol (n = 261) or placebo (n = 258). Bisoprolol was started at 1.25 mg orally daily and was titrated as tolerated during 4 sessions to a maximum dose of 5 mg/d, using a standardized protocol. Main Outcomes and Measures: The primary clinical outcome was the number of patient-reported COPD exacerbations treated with oral corticosteroids, antibiotics, or both during the 1-year treatment period. Safety outcomes included serious adverse events and adverse reactions. Results: Although the trial planned to enroll 1574 patients, recruitment was suspended from March 16, 2020, to July 31, 2021, due to the COVID-19 pandemic. Two patients in each group were excluded postrandomization. Among the 515 patients (mean [SD] age, 68 [7.9] years; 274 men [53%]; mean FEV1, 50.1%), primary outcome data were available for 514 patients (99.8%) and 371 (72.0%) continued taking the study drug. The primary outcome of patient-reported COPD exacerbations treated with oral corticosteroids, antibiotics, or both was 526 in the bisoprolol group, with a mean exacerbation rate of 2.03/y, vs 513 exacerbations in the placebo group, with a mean exacerbation rate of 2.01/y. The adjusted incidence rate ratio was 0.97 (95% CI, 0.84-1.13; P = .72). Serious adverse events occurred in 37 of 255 patients in the bisoprolol group (14.5%) vs 36 of 251 in the placebo group (14.3%; relative risk, 1.01; 95% CI, 0.62-1.66; P = .96). Conclusions and Relevance: Among people with COPD at high risk of exacerbation, treatment with bisoprolol did not reduce the number of self-reported COPD exacerbations requiring treatment with oral corticosteroids, antibiotics, or both. Trial Registration: isrctn.org Identifier: ISRCTN10497306.

Central Venous Access Devices for the Delivery of Systemic Anticancer Therapy: An Economic Evaluation.

OBJECTIVES: Patients undergoing long-term anticancer therapy typically require one of 3 venous access devices: Hickman-type device (HICK), peripherally inserted central catheter (PICC), or implantable chest wall port (PORT). Recent evidence has shown PORT is safer and improves patient satisfaction. However, PORT did not show improvement in quality-adjusted life-years and was more expensive. Decisions regarding cost-effectiveness in the United Kingdom are typically informed by a cost-per-quality-adjusted life-year metric. However, this approach is limited in its ability to capture the full range of relevant outcomes, especially in the context of medical devices. This study assessed the potential cost-effectiveness of HICK, PICC, and PORT in routine clinical practice. METHODS: This is a cost-consequence analysis to determine the trade-offs between the following outcomes: complication, infection, noninfection, chemotherapy interruption, unplanned device removals, health utilities, device insertion cost, follow-up cost, and total cost, using data from the Cancer and Venous Access clinical trial. We conducted value of implementation analysis of a PORT service. RESULTS: PORT was superior in terms of overall complication rate compared with both HICK (incidence rate ratio 0.422; 95% CI 0.286-0.622) and PICC (incidence rate ratio 0.295; 95% CI 0.189-0.458) and less likely to lead to an unplanned device removal. There was no difference in chemotherapy interruption or health utilities. Total cost with device in situ was lower on PORT than HICK (-£98.86; 95% CI -189.20 to -8.53) and comparable with PICC -£48.57 (95% CI -164.99 to 67.86). Value of implementation analysis found that PORT was likely to be considered cost-effective within the National Health Service. CONCLUSION: Decision makers should consider including PORT within the suite of venous access devices available within in the National Health Service.

Invasive Endotyping in Patients With Angina and No Obstructive Coronary Artery Disease: A Randomized Controlled Trial.

BACKGROUND: We investigated the usefulness of invasive coronary function testing to diagnose the cause of angina in patients with no obstructive coronary arteries. METHODS: Outpatients referred for coronary computed tomography angiography in 3 hospitals in the United Kingdom were prospectively screened. After coronary computed tomography angiography, patients with unobstructed coronary arteries, and who consented, underwent invasive endotyping. The diagnostic assessments included coronary angiography, fractional flow reserve (patient excluded if ≤0.80), and, for those without obstructive coronary artery disease, coronary flow reserve (abnormal <2.0), index of microvascular resistance (abnormal ≥25), and intracoronary infusion of acetylcholine (0.182, 1.82, and 18.2 µg/mL; 2 mL/min for 2 minutes) to assess for microvascular and coronary spasm. Participants were randomly assigned to disclosure of the results of the coronary function tests to the invasive cardiologist (intervention group) or nondisclosure (control group, blinded). In the control group, a diagnosis of vasomotor angina was based on medical history, noninvasive tests, and coronary angiography. The primary outcome was the between-group difference in the reclassification rate of the initial diagnosis on the basis of coronary computed tomography angiography versus the final diagnosis after invasive endotyping. The Seattle Angina Questionnaire summary score and Treatment Satisfaction Questionnaire for Medication were secondary outcomes. RESULTS: Of 322 eligible patients, 250 (77.6%) underwent invasive endotyping; 19 (7.6%) had obstructive coronary disease, 127 (55.0%) had microvascular angina, 27 (11.7%) had vasospastic angina, 17 (7.4%) had both, and 60 (26.0%) had no abnormality. A total of 231 patients (mean age, 55.7 years; 64.5% women) were randomly assigned and followed up (median duration, 19.9 [12.6-26.9] months). The clinician diagnosed vasomotor angina in 51 (44.3%) patients in the intervention group and in 55 (47.4%) patients in the control group. After randomization, patients in the intervention group were 4-fold (odds ratio, 4.05 [95% CI, 2.32-7.24]; P<0.001) more likely to be diagnosed with a coronary vasomotor disorder; the frequency of this diagnosis increased to 76.5%. The frequency of normal coronary function (ie, no vasomotor disorder) was not different between the groups before randomization (51.3% versus 50.9%) but was reduced in the intervention group after randomization (23.5% versus 50.9%, P<0.001). At 6 and 12 months, the Seattle Angina Questionnaire summary score in the intervention versus control groups was 59.2±24.2 (2.3±16.2 change from baseline) versus 60.4±23.9 (4.6±16.4 change) and 63.7±23.5 (4.7±14.7 change) versus 66.0±19.3 (7.9±17.1 change), respectively, and not different between groups (global P=0.36). Compared with the control group, global treatment satisfaction was higher in the intervention group at 12 months (69.9±22.8 versus 61.7±26.9, P=0.013). CONCLUSIONS: For patients with angina and no obstructive coronary arteries, a diagnosis informed by invasive functional assessment had no effect on long-term angina burden, whereas treatment satisfaction improved. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03477890.

The coronary microvascular angina cardiovascular magnetic resonance imaging trial: Rationale and design.

BACKGROUND: Coronary microvascular dysfunction may cause myocardial ischemia with no obstructive coronary artery disease (INOCA). If functional testing is not performed INOCA may pass undetected. Stress perfusion cardiovascular MRI (CMR) quantifies myocardial blood flow (MBF) but the clinical utility of stress CMR in the management of patients with suspected angina with no obstructive coronary arteries (ANOCA) is uncertain. OBJECTIVES: First, to undertake a diagnostic study using stress CMR in patients with ANOCA following invasive coronary angiography and, second, in a nested, double-blind, randomized, controlled trial to assess the effect of disclosure on the final diagnosis and health status in the longer term. DESIGN: All-comers referred for clinically indicated coronary angiography for the investigation of suspected coronary artery disease will be screened in 3 regional centers in the United Kingdom. Following invasive coronary angiography, patients with ANOCA who provide informed consent will undergo noninvasive endotyping using stress CMR within 3 months of the angiogram. DIAGNOSTIC STUDY: Stress perfusion CMR imaging to assess the prevalence of coronary microvascular dysfunction and clinically significant incidental findings in patients with ANOCA. The primary outcome is the between-group difference in the reclassification rate of the initial diagnosis based on invasive angiography versus the final diagnosis after CMR imaging. RANDOMIZED, CONTROLLED TRIAL: Participants will be randomized to inclusion (intervention group) or exclusion (control group) of myocardial blood flow to inform the final diagnosis. The primary outcome of the clinical trial is the mean within-subject change in the Seattle Angina Questionnaire summary score (SAQSS) at 6 months. Secondary outcome assessments include the EUROQOL EQ-5D-5L questionnaire, the Brief Illness Perception Questionnaire (Brief-IPQ), the Treatment Satisfaction Questionnaire (TSQM-9), the Patient Health Questionnaire-4 (PHQ-4), the Duke Activity Status Index (DASI), the International Physical Activity Questionnaire- Short Form (IPAQ-SF), the Montreal Cognitive Assessment (MOCA) and the 8-item Productivity Cost Questionnaire (iPCQ). Health and economic outcomes will be assessed using electronic healthcare records. VALUE: To clarify if routine stress perfusion CMR imaging reclassifies the final diagnosis in patients with ANOCA and whether this strategy improves symptoms, health-related quality of life and health economic outcomes. CLINICALTRIALS: GOV: NCT04805814.

Health financing challenges in Southeast Asian countries for universal health coverage: a systematic review.

BACKGROUND: Universal Health Coverage (UHC) has received much attention and many countries are striving to achieve it. The Southeast Asian region, in particular, comprises many developing countries with limited resources, exacerbating challenges around attaining UHC. This paper aims to specifically explore the health financing challenges these countries face in achieving UHC via a systematic review approach and formulate recommendations that will be useful for policymakers. METHODS: The systematic review followed the guidelines as recommended by PRISMA. The narrative synthesis approach was used for data synthesis, followed by identifying common themes. RESULTS: The initial search returned 160 articles, and 32 articles were included after the screening process. The identified challenges in health financing towards achieving UHC in the Southeast Asian region are categorised into six main themes, namely (1) Unsustainability of revenue-raising methods, (2) Fragmented health insurance schemes, (3) Incongruity between insurance benefits and people's needs, (4) Political and legislative indifference, (5) Intractable and rapidly rising healthcare cost, (6) Morally reprehensible behaviours. CONCLUSIONS: The challenges identified are diverse and therefore require a multifaceted approach. Regional collaborative efforts between countries will play an essential role in the progress towards UHC and in narrowing the inequity gap. At the national level, individual countries must work towards sustainable health financing strategies by leveraging innovative digital technologies and constantly adapting to dynamic health trends. REGISTRATION: This study is registered with PROSPERO, under registration number CRD42022336624.

MED12 mutation activates the tryptophan/kynurenine/AHR pathway to promote growth of uterine leiomyomas.

Uterine leiomyomas cause heavy menstrual bleeding, anemia, and pregnancy loss in millions of women worldwide. Driver mutations in the transcriptional mediator complex subunit 12 (MED12) gene in uterine myometrial cells initiate 70% of leiomyomas that grow in a progesterone-dependent manner. We showed a distinct chromatin occupancy landscape of MED12 in mutant MED12 (mut-MED12) versus WT-MED12 leiomyomas. Integration of cistromic and transcriptomics data identified tryptophan 2,3-dioxygenase (TDO2) as the top mut-MED12 target gene that was significantly upregulated in mut-MED12 leiomyomas when compared with adjacent myometrium and WT-MED12 leiomyomas. TDO2 catalyzes the conversion of tryptophan to kynurenine, an aryl hydrocarbon receptor (AHR) ligand that we confirmed to be significantly elevated in mut-MED12 leiomyomas. Treatment of primary mut-MED12 leiomyoma cells with tryptophan or kynurenine stimulated AHR nuclear translocation, increased proliferation, inhibited apoptosis, and induced AHR-target gene expression, whereas blocking the TDO2/kynurenine/AHR pathway by siRNA or pharmacological treatment abolished these effects. Progesterone receptors regulated the expression of AHR and its target genes. In vivo, TDO2 expression positively correlated with the expression of genes crucial for leiomyoma growth. In summary, activation of the TDO2/kynurenine/AHR pathway selectively in mut-MED12 leiomyomas promoted tumor growth and may inform the future development of targeted treatments and precision medicine.

Evaluating the use of intraoperative magnetic resonance imaging in paediatric brain tumour resection surgeries: a literature review.

Brain tumours are the most common solid neoplasm in children, posing a significant challenge in oncology due to the limited range of treatment. Intraoperative magnetic resonance imaging (iMRI) has recently emerged to aid surgical intervention in neurosurgery resection with the potential to delineate tumour boundaries. This narrative literature review aimed to provide an updated evaluation of the clinical implementation of iMRI in paediatric neurosurgical resection, with an emphasis on the extent of brain tumour resection, patient outcomes and its drawbacks. Databases including MEDLINE, PubMed, Scopus and Web of Science were used to investigate this topic with key terms: paediatric, brain tumour, and iMRI. Exclusion criteria included literature comprised of adult populations and the use of iMRI in neurosurgery in the absence of brain tumours. The limited body of research evaluating the clinical implementation of iMRI in paediatric cohorts has been predominantly positive. Current evidence demonstrates the potential for iMRI use to increase rates of gross total resection (GTR), assess the extent of resection, and improve patient outcomes, such as progression-free survival. Limitations regarding the use of iMRI include prolonged operation times and complications associated with head immobilisation devices. iMRI has the potential to aid in the achievement of maximal brain tumour resection in paediatric patients. Future prospective randomised controlled trials are necessary to determine the clinical significance and benefits of using iMRI during neurosurgical resection for clinical management of brain neoplasms in children.

Effect of Medication Therapy Management by Pharmaceutical Care on Blood Pressure and Cardiovascular Risk in Hypertension: A Systematic Review, Meta-Analysis, and Meta-Regression.

Medication therapy management by pharmaceutical care (MTM-PC) has been shown to improve the effectiveness of antihypertensive treatments. The aim was to answer the question: what are the MTM-PC models and their impact on hypertensive patients' outcomes? This is a systematic review with meta-analysis. The search strategies were run on 27 September 2022 in the following databases: PubMed, EMBASE, Scopus, LILACs, Central Cochrane Library, Web of Science; and International Pharmaceutical Abstracts. The quality and bias risk was assessed by the Downs and Black instrument. Forty-one studies met the eligibility criteria and were included, Kappa = 0.86; 95% CI, 0.66-1.0; (p < 0.001). Twenty-seven studies (65.9%) had MTM-PC models outlined by the clinical team, showing as characteristics the mean of 10.0 ± 10.7 months of follow-up of hypertensive patients, with 7.7 ± 4.9 consultations. Instruments to assess the quality of life measured the enhancement by 13.4 ± 10.7% (p = 0.047). The findings of the meta-analysis show a mean reduction of -7.71 (95% CI, -10.93 to -4.48) and -3.66 (95% CI, -5.51 to -1.80), (p < 0.001) in mmHg systolic and diastolic pressures, respectively. Cardiovascular relative risk (RR) over ten years was 0.561 (95% CI, 0.422 to 0.742) and RR = 0.570 (95% CI, 0.431 to 0.750), considering homogeneous studies, I² = 0%. This study shows the prevalence of MTM-PC models outlined by the clinical team, in which there are differences according to the models in reducing blood pressure and cardiovascular risk over ten years with the improvement in quality of life.

Plasma levels of coagulation factors VIII and IX and risk of venous thromboembolism: Systematic review and meta-analysis.

INTRODUCTION: The associations of plasma factor VIII (FVIII) and factor IX (FIX) levels with risk of venous thromboembolism (VTE) are not well defined. We performed a systematic review and meta-analysis of these associations. METHODS: Random effects inverse-variance weighted meta-analysis was used to estimate pooled odds ratios for comparisons across equal quartiles of the distributions and 90 % thresholds (higher versus lower), and for testing linear trends. RESULTS: Among 15 studies (5327 cases) the pooled odds ratio of VTE for the fourth versus first quarter was 3.92 (95 % confidence interval 1.61, 5.29) for FVIII level; and among 7 studies (3498 cases) 1.57 (1.32, 1.87) for FIX level. Comparing factor levels above, versus below, the 90th percentile, the estimated pooled odds ratios were 3.00 (2.10, 4.30) for FVIII; 1.77 (1.22, 2.56) for FIX; and 4.56 (2.73, 7.63) for both FVIII and FIX considered jointly. CONCLUSIONS: We confirm increases in risk of VTE across population distributions of FVIII and FIX levels. Levels above the 90th percentile have almost twice the risk for FIX level compared to levels below; three-fold risk for FVIII level; and almost five-fold risk for both FVIII and FIX levels elevated.

Stroke resource utilisation and all-cause mortality in Thailand 2017-2020: A retrospective, cross-sectional study.

OBJECTIVE: To determine resource utilisation, costs and all-cause mortality related to stroke in Thailand. DESIGN: Retrospective, cross-sectional study. SETTING AND PARTICIPANTS: Patients with first-ever stroke in the Thai national claims database between 2017 and 2020 were included for analysis. No individuals were involved. METHODS: We estimated annual treatment costs using two-part models. Survival analysis for all-cause mortality was performed. RESULTS: We identified 386 484 patients with incident stroke of which 56% were men. Mean age was 65 years and ischaemic stroke was the most common subtype. Mean annual cost per patient was 37 179 Thai Baht (95% CI: 36 988 to 37 370). Haemorrhagic stroke was predominantly observed in the youngest age groups with the highest estimated mean annual cost. Patients with haemorrhagic stroke also had a longer length of stay (LOS) in hospital and an increased risk of mortality. Key cost drivers were identified to be age, LOS, comorbidity and thrombolysis. Costs were lower in patients who received rehabilitation; however, only 32% of patients received rehabilitation services. The 4-year survival rate of all stroke types was 66.5% (95% CI: 64.3% to 66.7%). Older age, high comorbidity score, long LOS and being treated outside the Bangkok area were factors associated with significantly increased mortality risk, while receiving thrombolysis or rehabilitation was associated with a decreased risk of death. CONCLUSION: The highest mean cost per patient was found in patients with haemorrhagic stroke. Receiving rehabilitation was associated with lower cost and mortality risk. Rehabilitation and disability outcomes should be improved to ensure an enhancement of health outcomes and efficient use of resources.

MetaBayesDTA: codeless Bayesian meta-analysis of test accuracy, with or without a gold standard.

BACKGROUND: The statistical models developed for meta-analysis of diagnostic test accuracy studies require specialised knowledge to implement. This is especially true since recent guidelines, such as those in Version 2 of the Cochrane Handbook of Systematic Reviews of Diagnostic Test Accuracy, advocate more sophisticated methods than previously. This paper describes a web-based application - MetaBayesDTA - that makes many advanced analysis methods in this area more accessible. RESULTS: We created the app using R, the Shiny package and Stan. It allows for a broad array of analyses based on the bivariate model including extensions for subgroup analysis, meta-regression and comparative test accuracy evaluation. It also conducts analyses not assuming a perfect reference standard, including allowing for the use of different reference tests. CONCLUSIONS: Due to its user-friendliness and broad array of features, MetaBayesDTA should appeal to researchers with varying levels of expertise. We anticipate that the application will encourage higher levels of uptake of more advanced methods, which ultimately should improve the quality of test accuracy reviews.

Effects on heavy menstrual bleeding and pregnancy of uterine artery embolization (UAE) or myomectomy for women with uterine fibroids wishing to avoid hysterectomy: The FEMME randomized controlled trial.

OBJECTIVE: To determine treatment options (myomectomy vs. uterine artery embolization (UAE)) for women wishing to avoid hysterectomy. METHODS: A multicenter randomized controlled trial was conducted on 254 women and data were collected on fibroid-specific quality of life (UFS-QOL), loss of menstrual blood, and pregnancy. RESULTS: At 4 years, the mean difference in the UFS-QOL was 5.0 points (95% confidence interval (CI) -1.4 to 11.5; P = 0.13) in favor of myomectomy. This was not statistically significant as it was at 2 years. There were no differences in bleeding scores, rates of amenorrhea, or heavy bleeding. Of those who were still menstruating, the majority reported regular or fairly regular periods: 36 of 48 (75%) in the UAE group and 30 of 39 (77%) in the myomectomy group. Twelve women after UAE and six women after myomectomy became pregnant (4 years) with seven and five live births, respectively (hazard ratio 0.48, 95% CI 0.18-1.28). There was no difference between the levels of hormones associated with the uterine reserve in each group. CONCLUSION: Leiomyoma are common in reproductive-aged women, causing heavy menses and subfertility. Among women with uterine fibroids, myomectomy resulted in better fibroid-related quality of life at 4 years, compared with UAE but the treatments decreased menstrual bleeding equally. There was also no significant difference in the impact of treatment on ovarian reserve.

Implementation of a national smoke-free prison policy: an economic evaluation within the Tobacco in Prisons (TIPs) study.

OBJECTIVE: To determine the cost-effectiveness of a smoke-free prison policy in Scotland, through assessments of the trade-offs between costs (healthcare and non-healthcare-related expenditure) and outcomes (health and non-health-related non-monetary consequences) of implementing the policy. DESIGN: A health economic evaluation consisting of three analyses (cost-consequence, cost-effectiveness and cost-utility), from the perspectives of the healthcare payer, prison service, people in custody and operational staff, assessed the trade-offs between costs and outcomes. Costs associated with the implementation of the policy, healthcare resource use and personal spend on nicotine products were considered, alongside health and non-health outcomes. The cost-effectiveness of the policy was evaluated over 12-month and lifetime horizons (short term and long term). SETTING: Scotland's national prison estate. PARTICIPANTS: People in custody and operational prison staff. INTERVENTION: Implementation of a comprehensive (indoor and outdoor) smoke-free policy. MAIN OUTCOME MEASURES: Concentration of secondhand smoke, health-related quality of life (health utilities and quality-adjusted life-years (QALY)) and various non-health outcomes (eg, incidents of assaults and fires). RESULTS: The short-term analyses suggest cost savings for people in custody and staff, improvements in concentration of secondhand smoke, with no consistent direction of change across other outcomes. The long-term analysis demonstrated that implementing smoke-free policy was cost-effective over a lifetime for people in custody and staff, with approximate cost savings of £28 000 and £450, respectively, and improvement in health-related quality of life of 0.971 QALYs and 0.262, respectively. CONCLUSION: Implementing a smoke-free prison policy is cost-effective over the short term and long term for people in custody and staff.

Availability of stroke services and hospital facilities at different hospital levels in Thailand: a cross-sectional survey study.

BACKGROUND: Stroke has one of the biggest burden of disease in Thailand and all health regions have been tasked to develop their service delivery to achieve the national key performance indicators set out by the Thai service plan strategy 2018-2022. Our aim was to characterise stroke services and hospital facilities by investigating differences in facilities across different hospital levels in Thailand. METHODS: Self-complete questionnaires were distributed to 119 hospitals in 12 health regions between November-December 2019. Participants were health professionals whose main responsibilities are related to stroke service provision in their hospital. Descriptive statistics were used to report differences of stroke service provision between advanced-level, standard-level and mid-level referral hospitals. RESULTS: Thirty-eight (32% response rate) completed questionnaires were returned. All advanced-level, standard-level (100%) and 55% of mid-level referral hospitals provided stroke units. Neurologists were available in advanced-level (100%) and standard-level referral hospitals (50%). Standard-level and mid-level referral hospitals only had a quarter of rehabilitation physicians compared to advanced-level referral hospital. Home-based rehabilitation was provided at 100% in mid-level but only at 16% and 50% in advanced-level and standard-level referral hospitals. CONCLUSIONS: Setting up a stroke unit, as a national goal that was set out in the service plan strategy 2018-2022, was achieved fully (100%) in advanced-level and standard-level referral hospitals including key essential supportive components. However, capacity in hospitals was found to be limited and stroke service delivery needs to be improved especially at mid-level referral hospitals. This should include regular organisational surveys and the use of electronic records to facilitate monitoring of clinical/health outcomes of patients.

How do multiple long-term conditions impact on the cost-of-illness in early rheumatoid arthritis?

OBJECTIVE: Multiple long-term conditions (MLTCs) are prevalent in rheumatoid arthritis (RA) and associated with worse outcomes and greater economic burden. However, little is known about the impact of MLTCs on the cost-of-illness (COI) in early RA, including direct and indirect costs. The objective of this study was to quantify this impact on COI. METHODS: The Scottish Early Rheumatoid Arthritis study is a national cohort of adults with new-onset RA. Direct costs were estimated applying relevant unit costs to health resource utilisation; indirect costs were measured by productivity loss due to health conditions. Two-part models were used, adjusting for age, gender, baseline functional disability and health-related quality of life. The Charlson Comorbidity Index score was calculated using ICD-10 diagnoses. Individuals were defined as 'RA alone', 'RA plus LTC' and 'RA plus MLTCs' according to the number of coexisting LTCs. RESULTS: Data were available for 818 participants. Average annualised direct costs incurred by people with early RA plus MLTCs (£4444; 95% CI £3100 to £6371) were twice as, and almost five times higher than, those with a single LTC (£2184; 95% CI £1596 to £2997) and those without LTC (£919; 95% CI £694 to £1218), respectively. Indirect costs incurred by RA plus MLTCs (£842; 95% CI £377to £1521) were 3.1 times higher than RA alone (£530; 95% CI £273to £854). The relative proportion of direct costs increased with LTC category, ranging from 77.2% to 84.1%. In addition to increased costs with LTCs, costs also increased with age and were higher for men regardless of LTC category. CONCLUSIONS: MLTCs impact on COI early in the course of RA. The presence of LTCs is associated with significant increases in both direct and indirect costs among people with early RA.

Economic Evaluation of Multiple-Pharmacogenes Testing for the Prevention of Adverse Drug Reactions in People Living with HIV.

Purpose: Pharmacogenetics (PGx) testing is one of the methods for determining whether individuals are at risk of adverse drug reactions (ADRs). It has been reported that multiple-PGx testing, a sequencing technology, has a higher predictive value than single-PGx testing. Therefore, this study aimed to determine the most cost-effective PGx testing strategies for preventing drug-induced serious ADRs in human immunodeficiency virus (HIV)-infected patients. Patients and Methods: Potential strategies, including 1) single-PGx esting (ie, HLA-B*57:01 testing before prescribing abacavir, HLA-B*13:01 testing before prescribing co-trimoxazole and dapsone, and NAT2 testing before prescribing isoniazid) and 2) multiple-PGx testing as a combination of four single-gene PGx tests in one panel, were all compared to no PGx testing (current practice). To evaluate total cost in Thai baht (THB) and quality-adjusted life years (QALYs) for each strategy-based approach to a societal perspective, a hybrid decision tree and Markov model was constructed. Incremental cost-effectiveness ratios (ICERs) were estimated. Uncertainty, threshold, and scenario analyses were all performed. Results: Before prescribing HIV therapy, providing single or multiple-PGx testing might save roughly 68 serious ADRs per year, and the number needed to screen (NNS) to avoid one serious ADR was 40. Consequently, approximately 35% and 40% of the cost of ADR treatment could be avoided by the implementation of single- and multiple-PGx testing, respectively. Compared with no PGx testing strategy, the ICERs were 146,319 THB/QALY gained for single-PGx testing and 152,014 THB/QALY gained for multiple-PGx testing. Moreover, the probability of multiple-PGx testing being cost-effective was 45% at the Thai willingness to pay threshold of 160,000 THB per QALY. Threshold analyses showed that multiple-PGx testing remained cost-effective under the range of cost, sensitivity at 0.95-1.00 and specificity at 0.98-1.00. Conclusion: Single and multiple-PGx testing might be cost-effective options for reducing the incidence of drug-induced serious ADRs in people living with HIV.

Effectiveness and Safety of Nonvitamin K Oral Anticoagulants Rivaroxaban and Apixaban in Patients with Venous Thromboembolism: A Meta-Analysis of Real-World Studies.

Background: Rivaroxaban and apixaban are the most widely used nonvitamin K oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE). This meta-analysis evaluates the effectiveness and safety of both NOACs versus standard of care (SoC) in real-world practice. Methods: Real-world evidence (RWE) studies were identified through a systematic literature review conducted between January 2012 and July 2020, using Embase, MEDLINE, and the websites of cardiological, hematological, and oncological associations. Eligible RWE studies recruited adult patients with deep vein thrombosis and/or pulmonary embolism and presented a comparison between rivaroxaban and apixaban versus SoC, consisting either of vitamin K antagonists, heparins, or combinations thereof. Hazard ratios (HRs) for the comparison between NOACs and SoC were extracted from the relevant studies or estimated based on the reported binary data. The between-treatment contrasts were reported as HRs with associated 95% confidence intervals. Results: A total of 65 RWE studies were identified and considered relevant for the meta-analysis. Compared with SoC, both rivaroxaban and apixaban were associated with reduced risks of recurrent VTE and a lower rate of major bleeding events. Patients treated with rivaroxaban were at a lower risk of all-cause death compared with those receiving SoC (HR = 0.56 [0.39-0.80]), while evidence for apixaban from the identified studies was insufficient to demonstrate a statistically significant change in mortality (HR = 0.66 [0.30-1.47]). Conclusion: This analysis indicates that in real-world practice, rivaroxaban and apixaban are associated with a lower risk of recurrent VTE and major bleeding events compared with SoC. Survival benefit in patients treated with rivaroxaban was also observed.

Disinvestment in healthcare: a scoping review of systematic reviews.

OBJECTIVES: Disinvestment from low value health technologies is growing globally. Diverse evidence gathering and assessment methods were used to implement disinvestment initiatives, however, less than half of the empirical studies report reduced use of the low-value services. This scoping review aimed to synthesize the information from available reviews on the concepts and purposes of disinvestment in healthcare, the approaches and methods used, the role of stakeholders and facilitators and barriers in its implementation. METHODS: This scoping review was guided by the Joanna Briggs Institute Manual for Evidence Synthesis and PRISMA statement for scoping review. Published reviews on disinvestment were identified from scientific databases including health technology assessment (HTA) Web sites using the terms "disinvestment," "health technology reassessment," and "healthcare." The data obtained was synthesized narratively to identify similarities and differences across the approaches based on the prespecified categories. RESULTS: Seventeen reviews were included with thirty-four initiatives identified across sixteen countries at various levels of implementation and responsible agencies for the activities. Two most used methods to facilitate disinvestment decisions are Programme Budgeting and Marginal Analysis (PBMA) and HTA. Stakeholder involvement is the most important aspect to be addressed, as it acts as both facilitator and barrier in disinvestment initiatives implementation. CONCLUSIONS: Disinvestment programs have been implemented at multilevel, involving multistakeholders and using multiple methods such as PBMA and HTA. However, there is a lack of clarity on the additional dimensions of technical analysis related to these tools. Further research could focus on technology optimization in healthcare as part of overall health technology management.