Thermal escape box: A cost-benefit evaluation paradigm for investigating thermosensation and thermal pain.

Thermosensation, the ability to detect and estimate temperature, is an evolutionarily conserved process that is essential for survival. Thermosensing is impaired in various pain syndromes, resulting in thermal allodynia, the perception of an innocuous temperature as painful, or thermal hyperalgesia, an exacerbated perception of a painful thermal stimulus. Several behavioral assays exist to study thermosensation and thermal pain in rodents, however, most rely on reflexive withdrawal responses or the subjective quantification of spontaneous nocifensive behaviors. Here, we created a new apparatus, the thermal escape box, which can be attached to temperature-controlled plates and used to assess temperature-dependent effort-based decision-making. The apparatus consists of a light chamber with an opening that fits around temperature-controlled plates, and a small entryway into a dark chamber. A mouse must choose to stay in a brightly lit aversive area or traverse the plates to escape to the enclosed dark chamber. We quantified escape latencies of adult C57Bl/6 mice at different plate temperatures from video recordings and found they were significantly longer at 5 °C, 18 °C, and 52 °C, compared to 30 °C, a mouse's preferred ambient temperature. Differences in escape latencies were abolished in male Trpm8-/- mice and in male Trpv1-/- animals. Finally, we show that chronic constriction injury procedures or oxaliplatin treatement significantly increased escape latencies at cold temperatures compared to controls, the later of which was prevented by the analgesic meloxicam. This demonstrates the utility of this assay in detecting cold pain. Collectively, our study has identified a new and effective tool that uses cost-benefit valuations to study thermosensation and thermal pain.

[Cost-effectiveness analysis of fracture liaison services in Catalonia]. / Análisis de coste-efectividad de las Unidades de Coordinación de Fracturas en Cataluña.

OBJECTIVE: To assess the cost-effectiveness of Fracture Liaison Service (FLS) compared to the standard of care for secondary prevention of fragility fractures form the perspective of the Catalan Health Service. METHODS: Cost-utility assessment through a Markov model that simulated disease progression of a patients' cohort candidates to initiate antiosteoporotic treatment after a fragility fracture. A time horizon of 10 years and a 6-month duration per cycle was established. Clinical, economics and quality of life parameters were obtained from the literature and derived from four Catalan FLS. The Catalan Health Service perspective was adopted, considering direct health costs expressed in 2022 euros. A 3% discount rate was applied on costs and outcomes. Uncertainty was assessed through multiple sensitivity analyses. RESULTS: Compared to the standard of care, FLS would promote antiosteoporotic initiation and persistence, reducing the incidence and mortality associated with subsequent fragility fractures. This incremental clinical benefit was estimated at 0.055 years and 0.112 quality-adjusted life years (QALYs) per patient. A higher cost (€1,073.79 per patient) was estimated, resulting into an incremental cost-utility ratio of €9,602.72 per QALYs gained. The sensitivity analyses performed were consistent, corroborating the robustness and conservative approach of the base-case. CONCLUSIONS: The introduction of FLS for the secondary prevention of FF would represent a cost-effective strategy from the Catalan Health Service perspective.

Improving perioperative acetaminophen administration for safer and cost-effective multimodal analgesia in pediatric surgery: A QI initiative.

BACKGROUND: The use of acetaminophen in the perioperative period has emerged as an attractive option for providing safer and cost-effective analgesia in children. AIMS: The primary aim of our project was to increase the use of acetaminophen (both oral and intravenous) in the perioperative period from a baseline of 39.5% to 50% for all surgical patients within 24 months. The secondary aim was to increase the use of enteral acetaminophen from 10% to 52.5% during the same period. METHODS: A multidisciplinary team was formed, and model for improvement was chosen as the QI methodology. The primary measure was the total percentage of surgical patients receiving any form of perioperative acetaminophen, while our secondary measure was the percentage use of oral acetaminophen administration. We also tracked the average maximum PACU (Post Anesthesia Care Unit) pain scores and the percentage of patients receiving IV opioids. Multiple interventions were conducted, including education, increasing the availability of acetaminophen, and optimizing the electronic medical record (EMR). Monthly data was collected using an automated report in the EMR. RESULTS: We successfully achieved our goal, increasing the use of acetaminophen from 39.5% to 70% within four months. Despite some fluctuations, by the end of 24 months, we not only met but surpassed our goal, with 63% of patients receiving perioperative acetaminophen. Similarly, the usage of oral acetaminophen increased from a baseline of 10% to 78%. Our average maximum PACU pain scores improved from 5.4 to 5.2, and the percentage of patients receiving rescue opioids decreased from 15.4 to 13.1. CONCLUSION: We successfully achieved and sustained our goals of improving acetaminophen use for our surgical patients without worsening pain scores or worsening use of intravenous opioids. Future directions include further refining our strategies and exploring additional opportunities to optimize pain management in pediatric perioperative settings.

Center Hemodialysis Versus Peritoneal Dialysis: A Cost-Utility Analysis.

Introduction Kidney replacement therapy (KRT) is needed for patients with end-stage kidney disease. While it is clear that kidney transplantation remains the gold standard in KRT, data comparing the cost-utility of peritoneal dialysis (PD) and hemodialysis (HD) are scarce. No such analysis has been performed for German patients.  Methods We used aggregated data generated by the Short Form 36 Health Survey (SF-36) for quality of life and insurance claims to evaluate mortality and economic impact. Quality-adjusted life years (QALY) and cost-utility were calculated accordingly.  Results PD is superior to HD within all dimensions of the SF-36, both in terms of QALY and cost-utility. The difference in cost per QALY between the aggregated physical dimensions (€50,671.54 vs. €39,745.77) is greater than that of the aggregated mental dimensions (€31,638.75 vs. €25,287.63). However, there is considerable variability among patients.  Conclusion From a health-economic point of view, PD should be preferred over HD when deciding on the KRT modality for the patient. This is not reflected in current practice, though. However, interindividual differences and patient preferences should be considered in the decision.

Evaluation of venous thromboembolism risk assessment models for hospital inpatients: the VTEAM evidence synthesis.

Background: Pharmacological prophylaxis during hospital admission can reduce the risk of acquired blood clots (venous thromboembolism) but may cause complications, such as bleeding. Using a risk assessment model to predict the risk of blood clots could facilitate selection of patients for prophylaxis and optimise the balance of benefits, risks and costs. Objectives: We aimed to identify validated risk assessment models and estimate their prognostic accuracy, evaluate the cost-effectiveness of different strategies for selecting hospitalised patients for prophylaxis, assess the feasibility of using efficient research methods and estimate key parameters for future research. Design: We undertook a systematic review, decision-analytic modelling and observational cohort study conducted in accordance with Enhancing the QUAlity and Transparency Of health Research (EQUATOR) guidelines. Setting: NHS hospitals, with primary data collection at four sites. Participants: Medical and surgical hospital inpatients, excluding paediatric, critical care and pregnancy-related admissions. Interventions: Prophylaxis for all patients, none and according to selected risk assessment models. Main outcome measures: Model accuracy for predicting blood clots, lifetime costs and quality-adjusted life-years associated with alternative strategies, accuracy of efficient methods for identifying key outcomes and proportion of inpatients recommended prophylaxis using different models. Results: We identified 24 validated risk assessment models, but low-quality heterogeneous data suggested weak accuracy for prediction of blood clots and generally high risk of bias in all studies. Decision-analytic modelling showed that pharmacological prophylaxis for all eligible is generally more cost-effective than model-based strategies for both medical and surgical inpatients, when valuing a quality-adjusted life-year at £20,000. The findings were more sensitive to uncertainties in the surgical population; strategies using risk assessment models were more cost-effective if the model was assumed to have a very high sensitivity, or the long-term risks of post-thrombotic complications were lower. Efficient methods using routine data did not accurately identify blood clots or bleeding events and several pre-specified feasibility criteria were not met. Theoretical prophylaxis rates across an inpatient cohort based on existing risk assessment models ranged from 13% to 91%. Limitations: Existing studies may underestimate the accuracy of risk assessment models, leading to underestimation of their cost-effectiveness. The cost-effectiveness findings do not apply to patients with an increased risk of bleeding. Mechanical thromboprophylaxis options were excluded from the modelling. Primary data collection was predominately retrospective, risking case ascertainment bias. Conclusions: Thromboprophylaxis for all patients appears to be generally more cost-effective than using a risk assessment model, in hospitalised patients at low risk of bleeding. To be cost-effective, any risk assessment model would need to be highly sensitive. Current evidence on risk assessment models is at high risk of bias and our findings should be interpreted in this context. We were unable to demonstrate the feasibility of using efficient methods to accurately detect relevant outcomes for future research. Future work: Further research should evaluate routine prophylaxis strategies for all eligible hospitalised patients. Models that could accurately identify individuals at very low risk of blood clots (who could discontinue prophylaxis) warrant further evaluation. Study registration: This study is registered as PROSPERO CRD42020165778 and Researchregistry5216. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127454) and will be published in full in Health Technology Assessment; Vol. 28, No. 20. See the NIHR Funding and Awards website for further award information.

People who are admitted to hospital are at risk of blood clots that can cause serious illness or death. Patients are often given low doses of blood-thinning drugs to reduce this risk. However, these drugs can cause side effects, such as bleeding. Hospitals currently use complex risk assessment models (risk scores, which usually include patient, disease, mobility and intervention factors) to determine the individual risk of blood clots and identify people most likely to benefit from blood-thinning drugs. There are a lot of different risk scores and we do not know which one is best. We also do not know how these scores compare to each other or whether using scores to decide who should get blood-thinning drugs provides good value for money to the NHS. We reviewed all previous studies of risk scores. We found that they did not predict blood clots very well and we could not recommend one score over another. We then created a mathematical model to simulate the use of blood-thinning drugs in people admitted to hospital. The model suggested that giving blood-thinning drugs to everyone who could have them would probably provide the best value for money, in medical patients. Our findings were the same, but less certain, for surgical patients. We also collected information from four NHS hospitals to explore possibilities for future research. Our work showed that routinely collected electronic data on blood clots and bleeding events is not very accurate and that using different scores could result in variable use of blood-thinning medications. Our findings suggest that it may be better value to the NHS and better for patients if we were to offer blood-thinning medications to everyone on admission to hospital, without using any risk score. However, this approach needs further research to ensure it is safe and effective. Such research would not be able to rely on routine electronic data to identify blood clots or bleeding events, in isolation.

A life cycle cost analysis of different shore power incentive policies on both shore and ship sides based on system dynamics and a Chinese port case.

Shore power (SP) is widely recognized as an efficient strategy for reducing air pollution in port areas. Unfortunately, the adoption of SP has been relatively low, resulting in limited emission reductions and financial losses. To address these challenges, this paper focuses on enhancing the utilization rate of SP, which is meaningful for emission control and environmental protection. This paper combines system dynamics with a study of the benefits of SP, which bridges the research gap to some extent. We propose a system dynamics model that assesses the impact of various incentive policies on the economic and environmental benefits of SP. The model considers the life cycle cost and comprises four subsystems. By conducting a case study on Nansha Port, we find that price subsidies are more effective than construction subsidies in overcoming economic barriers. Furthermore, we observe that the overall economic benefits only increase when the electricity price decreases. This is because lowering the electricity price enhances the profitability of ships without negatively affecting port revenue. Additionally, it is the proportion of the electricity price and service price that determines the overall economic benefits, rather than the SP price itself. Hence, it is recommended to provide preferential subsidies for the electricity price.

Patient-reported outcome measures for monitoring primary care patients with depression: the PROMDEP cluster RCT and economic evaluation.

Background: Guidelines on the management of depression recommend that practitioners use patient-reported outcome measures for the follow-up monitoring of symptoms, but there is a lack of evidence of benefit in terms of patient outcomes. Objective: To test using the Patient Health Questionnaire-9 questionnaire as a patient-reported outcome measure for monitoring depression, training practitioners in interpreting scores and giving patients feedback. Design: Parallel-group, cluster-randomised superiority trial; 1 : 1 allocation to intervention and control. Setting: UK primary care (141 group general practices in England and Wales). Inclusion criteria: Patients aged ≥ 18 years with a new episode of depressive disorder or symptoms, recruited mainly through medical record searches, plus opportunistically in consultations. Exclusions: Current depression treatment, dementia, psychosis, substance misuse and risk of suicide. Intervention: Administration of the Patient Health Questionnaire-9 questionnaire with patient feedback soon after diagnosis, and at follow-up 10-35 days later, compared with usual care. Primary outcome: Beck Depression Inventory, 2nd edition, symptom scores at 12 weeks. Secondary outcomes: Beck Depression Inventory, 2nd edition, scores at 26 weeks; antidepressant drug treatment and mental health service contacts; social functioning (Work and Social Adjustment Scale) and quality of life (EuroQol 5-Dimension, five-level) at 12 and 26 weeks; service use over 26 weeks to calculate NHS costs; patient satisfaction at 26 weeks (Medical Informant Satisfaction Scale); and adverse events. Sample size: The original target sample of 676 patients recruited was reduced to 554 due to finding a significant correlation between baseline and follow-up values for the primary outcome measure. Randomisation: Remote computerised randomisation with minimisation by recruiting university, small/large practice and urban/rural location. Blinding: Blinding of participants was impossible given the open cluster design, but self-report outcome measures prevented observer bias. Analysis was blind to allocation. Analysis: Linear mixed models were used, adjusted for baseline depression, baseline anxiety, sociodemographic factors, and clustering including practice as random effect. Quality of life and costs were analysed over 26 weeks. Qualitative interviews: Practitioner and patient interviews were conducted to reflect on trial processes and use of the Patient Health Questionnaire-9 using the Normalization Process Theory framework. Results: Three hundred and two patients were recruited in intervention arm practices and 227 patients were recruited in control practices. Primary outcome data were collected for 252 (83.4%) and 195 (85.9%), respectively. No significant difference in Beck Depression Inventory, 2nd edition, score was found at 12 weeks (adjusted mean difference -0.46, 95% confidence interval -2.16 to 1.26). Nor were significant differences found in Beck Depression Inventory, 2nd Edition, score at 26 weeks, social functioning, patient satisfaction or adverse events. EuroQol-5 Dimensions, five-level version, quality-of-life scores favoured the intervention arm at 26 weeks (adjusted mean difference 0.053, 95% confidence interval 0.013 to 0.093). However, quality-adjusted life-years over 26 weeks were not significantly greater (difference 0.0013, 95% confidence interval -0.0157 to 0.0182). Costs were lower in the intervention arm but, again, not significantly (-£163, 95% confidence interval -£349 to £28). Cost-effectiveness and cost-utility analyses, therefore, suggested that the intervention was dominant over usual care, but with considerable uncertainty around the point estimates. Patients valued using the Patient Health Questionnaire-9 to compare scores at baseline and follow-up, whereas practitioner views were more mixed, with some considering it too time-consuming. Conclusions: We found no evidence of improved depression management or outcome at 12 weeks from using the Patient Health Questionnaire-9, but patients' quality of life was better at 26 weeks, perhaps because feedback of Patient Health Questionnaire-9 scores increased their awareness of improvement in their depression and reduced their anxiety. Further research in primary care should evaluate patient-reported outcome measures including anxiety symptoms, administered remotely, with algorithms delivering clear recommendations for changes in treatment. Study registration: This study is registered as IRAS250225 and ISRCTN17299295. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/42/02) and is published in full in Health Technology Assessment; Vol. 28, No. 17. See the NIHR Funding and Awards website for further award information.

Depression is common, can be disabling and costs the nation billions. The National Health Service recommends general practitioners who treat people with depression use symptom questionnaires to help assess whether those people are getting better over time. A symptom questionnaire is one type of patient-reported outcome measure. Patient-reported outcome measures appear to benefit people having therapy and mental health care, but this approach has not been tested thoroughly in general practice. Most people with depression are treated in general practice, so it is important to test patient-reported outcome measures there, too. In this study, we tested whether using a patient-reported outcome measure helps people with depression get better more quickly. The study was a 'randomised controlled trial' in general practices, split into two groups. In one group, people with depression completed the Patient Health Questionnaire, or 'PHQ-9', patient-reported outcome measure, which measures nine symptoms of depression. In the other group, people with depression were treated as usual without the Patient Health Questionnaire-9. We fed the results of the Patient Health Questionnaire-9 back to the people with depression themselves to show them how severe their depression was and asked them to discuss the results with the practitioners looking after them. We found no differences between the patient-reported outcome measure group and the control group in their level of depression; their work or social life; their satisfaction with care from their practice; or their use of medicines, therapy or specialist care for depression. However, we did find that their quality of life was improved at 6 months, and the costs of the National Health Service services they used were lower. Using the Patient Health Questionnaire-9 can improve patients' quality of life, perhaps by making them more aware of improvement in their depression symptoms, and less anxious as a result. Future research should test using a patient-reported outcome measure that includes anxiety and processing the answers through a computer to give practitioners clearer advice on possible changes to treatment for depression.

Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease: the ALL-HEART RCT and economic evaluation.

Background: Allopurinol is a xanthine oxidase inhibitor that lowers serum uric acid and is used to prevent acute gout flares in patients with gout. Observational and small interventional studies have suggested beneficial cardiovascular effects of allopurinol. Objective: To determine whether allopurinol improves major cardiovascular outcomes in patients with ischaemic heart disease. Design: Prospective, randomised, open-label, blinded endpoint multicentre clinical trial. Setting: Four hundred and twenty-four UK primary care practices. Participants: Aged 60 years and over with ischaemic heart disease but no gout. Interventions: Participants were randomised (1 : 1) using a central web-based randomisation system to receive allopurinol up to 600 mg daily that was added to usual care or to continue usual care. Main outcome measures: The primary outcome was the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes were non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, all-cause mortality, hospitalisation for heart failure, hospitalisation for acute coronary syndrome, coronary revascularisation, hospitalisation for acute coronary syndrome or coronary revascularisation, all cardiovascular hospitalisations, quality of life and cost-effectiveness. The hazard ratio (allopurinol vs. usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis. Results: From 7 February 2014 to 2 October 2017, 5937 participants were enrolled and randomised to the allopurinol arm (n = 2979) or the usual care arm (n = 2958). A total of 5721 randomised participants (2853 allopurinol; 2868 usual care) were included in the modified intention-to-treat analysis population (mean age 72.0 years; 75.5% male). There was no difference between the allopurinol and usual care arms in the primary endpoint, 314 (11.0%) participants in the allopurinol arm (2.47 events per 100 patient-years) and 325 (11.3%) in the usual care arm (2.37 events per 100 patient-years), hazard ratio 1.04 (95% confidence interval 0.89 to 1.21); p = 0.65. Two hundred and eighty-eight (10.1%) participants in the allopurinol arm and 303 (10.6%) participants in the usual care arm died, hazard ratio 1.02 (95% confidence interval 0.87 to 1.20); p = 0.77. The pre-specified health economic analysis plan was to perform a 'within trial' cost-utility analysis if there was no statistically significant difference in the primary endpoint, so NHS costs and quality-adjusted life-years were estimated over a 5-year period. The difference in costs between treatment arms was +£115 higher for allopurinol (95% confidence interval £17 to £210) with no difference in quality-adjusted life-years (95% confidence interval -0.061 to +0.060). We conclude that there is no evidence that allopurinol used in line with the study protocol is cost-effective. Limitations: The results may not be generalisable to younger populations, other ethnic groups or patients with more acute ischaemic heart disease. One thousand six hundred and thirty-seven participants (57.4%) in the allopurinol arm withdrew from randomised treatment, but an on-treatment analysis gave similar results to the main analysis. Conclusions: The ALL-HEART study showed that treatment with allopurinol 600 mg daily did not improve cardiovascular outcomes compared to usual care in patients with ischaemic heart disease. We conclude that allopurinol should not be recommended for the secondary prevention of cardiovascular events in patients with ischaemic heart disease but no gout. Future work: The effects of allopurinol on cardiovascular outcomes in patients with ischaemic heart disease and co-existing hyperuricaemia or clinical gout could be explored in future studies. Trial registration: This trial is registered as EU Clinical Trials Register (EudraCT 2013-003559-39) and ISRCTN (ISRCTN 32017426). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/36/41) and is published in full in Health Technology Assessment; Vol. 28, No. 18. See the NIHR Funding and Awards website for further award information.

The purpose of the ALL-HEART study was to determine whether giving allopurinol to people with ischaemic heart disease (also commonly known as coronary heart disease) would reduce their risk of having a heart attack, stroke or of dying from cardiovascular disease. Allopurinol is a medication usually given to patients with gout to prevent acute gout flares. It is not currently used to treat ischaemic heart disease. We randomly allocated people aged over 60 years with ischaemic heart disease to take up to 600 mg of allopurinol daily (in addition to their usual care) or to continue with their usual care. We then monitored participants for several years and recorded any major health events such as heart attacks, strokes and deaths. We obtained most of the follow-up data from centrally held electronic hospital admissions and death records, making the study easier for participants and more cost-efficient. We asked participants in both groups to complete questionnaires to assess their quality of life during the study. We also collected data to determine whether there was any economic benefit to the NHS of using allopurinol in patients with ischaemic heart disease. There was no difference in the risk of heart attacks, strokes or death from cardiovascular disease between the participants given allopurinol and those in the group continuing their usual care. We also found no difference in the risks of other cardiovascular events, deaths from any cause or quality-of-life measurements between the allopurinol and usual care groups. The results of the ALL-HEART study suggest that we should not recommend that allopurinol be given to people with ischaemic heart disease to prevent further cardiovascular events or deaths.

The impact of indirect benefits (reduced travel time, fuel use and emissions) in cost benefit analysis of road safety countermeasures.

OBJECTIVE: In cost benefit analysis of road safety countermeasures, all relevant effects on safety, travel time and environment have a substantial impact during economic appraisal. However, in the most widely used road safety appraisal tools such as SafetyAnalyst and International Road Assessment Programme (iRAP), indirect effects related to travel time and environment are not considered. Most economic appraisal studies conducted for road safety countermeasures consider only the safety benefits and ignore the indirect benefits due to lack of models to evaluate them. This study attempts to document the quantitative impact of indirect benefits during economic appraisal of road safety infrastructure investments particularly from the angle of reduced crashes. METHODS: To this effect, data from 9 European countries and the 20-year infrastructure improvement programme developed for the Netherlands are applied to demonstrate the impact of these indirect benefits through a quantitative study. RESULTS: The results show that indirect benefits increase the value of benefits by 7%, which improves the cost effectiveness of countermeasures. Consequently, the number of countermeasures selected for implementation are increased due to addition of these benefits. Travel time benefits constitute the largest share of indirect benefits with a contribution of 6% to the overall benefits due to countermeasure implementation. CONCLUSION: In conclusion, indirect benefits have a substantial impact on the computation of benefits and countermeasure selection process. In order to present improved business cases for road safety infrastructure investments, there is need to include these benefits during economic appraisal process. Travel time benefits have the highest portion of all indirect benefits compared to vehicle operating costs (VOCs) and emission benefits. The study recommends conducting more research related to travel time benefits due to countermeasure implementation.

Supply, demand and the economic effectiveness of urine-diverting technologies and products: A systematic literature review.

The broader adoption of urine-diverting technologies (UDTs) and related products has been proposed as a strategy for moving towards a more circular economy. While some studies have explored the performance of UDTs, the interconnected factors involving supply, demand, and economic feasibility of UDTs remain under-researched. Our systematic review addresses this gap. Our search identified only 64 relevant, peer-reviewed studies, 71 % of which addressed the supply side (primarily the technical aspect of UDTs) and 58 % of which addressed the demand side (focusing on consumers' perceptions). Approximately one-third (18) of these studies delved into the economic feasibility of UDTs, with only 9 employing a cost benefit analysis (CBA) framework. However, none of these studies have analysed the economic performance of UDTs that have been fully deployed, indicating a significant knowledge gap. Our review suggests that overcoming challenges in scaling up UDTs can be achieved by engaging those stakeholders driving the uptake, developing business cases that offer an overall understanding of both market and non-market benefits of UDTs, addressing technological constraints by optimising urine treatment options for efficiency and economic viability, and enhancing stakeholders' acceptance of UDTs.

A cost-benefit analysis of genetic screening test for breast cancer in Iran.

BACKGROUND: This study aimed to evaluate the implementation of the population- and family history (FH) -based screening for BReast CAncer (BRCA) in Iran, a country where less than 10% of breast cancer cases are attributable to a gene mutation. METHODS: This was an economic evaluation study. The Benefit-Cost Ratio (BCR) for genetic screening test strategies in Iranian women older than 30 was calculated. To this end, the monetary value of the test was estimated using the willingness-to-pay (WTP) approach using the contingent valuation method (CVM) by payment card. From a healthcare perspective, direct medical and non-medical costs were considered and a decision model for the strategies was developed to simulate the costs. A one-way sensitivity analysis assessed the robustness of the analysis. The data were analyzed using Excel 2010. RESULTS: 660 women were included for estimating WTP and 2,176,919 women were considered in the costing model. The cost per genetic screening test for population- and FH-based strategies was $167 and $8, respectively. The monetary value of a genetic screening test was $20 and it was $27 for women with a family history or gene mutation in breast cancer. The BCR for population-based and FH-based screening strategies was 0.12 and 3.37, respectively. Sensitivity analyses confirmed the robustness of the results. CONCLUSIONS: This study recommends the implementation of a FH-based strategy instead of a population-based genetic screening strategy in Iran, although a cascade genetic screening test strategy should be evaluated in future studies.

An integrated approach to prioritizing ecological restoration of abandoned mine lands based on cost-benefit analysis.

How to increase the usable land area by adhering to environmentally friendly ecological restoration of mines with limited funds is a challenge that many cities are currently facing. Cost-benefit analysis (CBA) can provide efficient and effective restoration decisions for abandoned mine land (AML) ecological restoration with limited financial resources. Thus, this study proposes an integrated approach for coupling ecological benefits and restoration costs, including hotspots/coldspots analysis based on five ecosystem services (ESs), landscape connectivity analysis based on graph theory model, hidden costs, and project implementation costs to prioritize AML restoration. The study was conducted on 54 abandoned mine lands (AMLs) in Chaoyang city, the ecological security barrier of China's northern sand prevention belt (NSPB). The comprehensive analysis prioritized the restoration of AMLs into four levels, of which 9 mines were in priority I, where restoration was recommended as a priority, and 22 mines were in priority II, where restoration could be carried out within the affordability of funds. In addition, our model indicates areas with high ecological benefits, in which the ecological source area (7423.66 km2) and the ecosystem service hotspots area (2028.44 km2) are mostly distributed in the southwestern part of Chaoyang city, the two mountain ranges of Songling mountain and Nuruerhu mountain. This study provides scientific spatial guidance to ensure that the AMLs realizes effective restoration and management.

Early switch from intravenous to oral antibiotic therapy in patients with cancer who have low-risk neutropenic sepsis: the EASI-SWITCH RCT.

Background: Neutropenic sepsis is a common complication of systemic anticancer treatment. There is variation in practice in timing of switch to oral antibiotics after commencement of empirical intravenous antibiotic therapy. Objectives: To establish the clinical and cost effectiveness of early switch to oral antibiotics in patients with neutropenic sepsis at low risk of infective complications. Design: A randomised, multicentre, open-label, allocation concealed, non-inferiority trial to establish the clinical and cost effectiveness of early oral switch in comparison to standard care. Setting: Nineteen UK oncology centres. Participants: Patients aged 16 years and over receiving systemic anticancer therapy with fever (≥ 38°C), or symptoms and signs of sepsis, and neutropenia (≤ 1.0 × 109/l) within 24 hours of randomisation, with a Multinational Association for Supportive Care in Cancer score of ≥ 21 and receiving intravenous piperacillin/tazobactam or meropenem for < 24 hours were eligible. Patients with acute leukaemia or stem cell transplant were excluded. Intervention: Early switch to oral ciprofloxacin (750 mg twice daily) and co-amoxiclav (625 mg three times daily) within 12-24 hours of starting intravenous antibiotics to complete 5 days treatment in total. Control was standard care, that is, continuation of intravenous antibiotics for at least 48 hours with ongoing treatment at physician discretion. Main outcome measures: Treatment failure, a composite measure assessed at day 14 based on the following criteria: fever persistence or recurrence within 72 hours of starting intravenous antibiotics; escalation from protocolised antibiotics; critical care support or death. Results: The study was closed early due to under-recruitment with 129 patients recruited; hence, a definitive conclusion regarding non-inferiority cannot be made. Sixty-five patients were randomised to the early switch arm and 64 to the standard care arm with subsequent intention-to-treat and per-protocol analyses including 125 (intervention n = 61 and control n = 64) and 113 (intervention n = 53 and control n = 60) patients, respectively. In the intention-to-treat population the treatment failure rates were 14.1% in the control group and 24.6% in the intervention group, difference = 10.5% (95% confidence interval 0.11 to 0.22). In the per-protocol population the treatment failure rates were 13.3% and 17.7% in control and intervention groups, respectively; difference = 3.7% (95% confidence interval 0.04 to 0.148). Treatment failure predominantly consisted of persistence or recurrence of fever and/or physician-directed escalation from protocolised antibiotics with no critical care admissions or deaths. The median length of stay was shorter in the intervention group and adverse events reported were similar in both groups. Patients, particularly those with care-giving responsibilities, expressed a preference for early switch. However, differences in health-related quality of life and health resource use were small and not statistically significant. Conclusions: Non-inferiority for early oral switch could not be proven due to trial under-recruitment. The findings suggest this may be an acceptable treatment strategy for some patients who can adhere to such a treatment regimen and would prefer a potentially reduced duration of hospitalisation while accepting increased risk of treatment failure resulting in re-admission. Further research should explore tools for patient stratification for low-risk de-escalation or ambulatory pathways including use of biomarkers and/or point-of-care rapid microbiological testing as an adjunct to clinical decision-making tools. This could include application to shorter-duration antimicrobial therapy in line with other antimicrobial stewardship studies. Trial registration: This trial is registered as ISRCTN84288963. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/140/05) and is published in full in Health Technology Assessment; Vol. 28, No. 14. See the NIHR Funding and Awards website for further award information.

Neutropenic sepsis, or infection with a low white blood cell count, can occur following cancer treatment. Usually patients receive treatment with intravenous antibiotics (antibiotics delivered into a vein) for two or more days. Patients at low risk of complications from their infection may be able to have a shorter period of intravenous antibiotics benefitting both patients and the NHS. The trial compared whether changing from intravenous to oral antibiotics (antibiotics taken by mouth as tablets or liquid) 12­24 hours after starting antibiotic treatment ('early switch') is as effective as usual care. Patients could take part if they had started intravenous antibiotics for low-risk neutropenic sepsis. Patients were randomly allocated to 'early switch' or to usual care. The main outcome measured was treatment failure. Treatment failure happened if fever persisted or recurred despite antibiotics, if patients needed to change antibiotics, if they needed to be re-admitted to hospital or needed to be admitted to intensive care within 14 days or died. We had originally intended that 628 patients would take part, but after review of the design of the study the number needed to take part was revised to 230. We were not able to complete the trial as planned as unfortunately only 129 patients took part. As the trial was smaller than expected we were not able to draw conclusions as to whether 'early switch' is no less effective than usual care. Our findings suggest that 'early switch' might result in a shorter time in hospital initially; however, treatment failure was more likely to occur, meaning some patients had to return to hospital for further antibiotics. There were no differences in side effects and no serious complications from treatment or treatment failure (such as intensive care admission or death) among the 65 patients in the 'early switch' group. Patients were satisfied with 'early switch'. Early switch may be a treatment option for some patients with low-risk neutropenic sepsis who would prefer a shorter duration of hospital admission but accept a risk of needing hospital re-admission.

Revolutionizing cancer treatment in India: Evaluating the unmet need, economics, and a roadmap for project implementation of particle therapy.

INTRODUCTION: This study aims to quantitatively assess eligible patients and project the demand for particle therapy facilities in India from 2020 to 2040. In addition, an economic analysis evaluates the financial feasibility of implementing this technology. The study also examines the prospective benefits and challenges of adopting this technology in India. METHODOLOGY: Cancer incidence and projected trends were analyzed for pediatric patients using the Global Childhood Cancer microsimulation model and adult patients using the Globocan data. Economic cost evaluation is performed for large-scale combined particle (carbon and proton-three room fixed-beam), large-scale proton (one gantry and two fixed-beam), and small-scale proton (one gantry) facility. RESULTS: By 2040, the estimated number of eligible patients for particle therapy is projected to reach 161,000, including approximately 14,000 pediatric cases. The demand for particle therapy facilities is projected to rise from 81 to 97 in 2020 to 121 to 146 by 2040. The capital expenditure is estimated to be only 3.7 times that of a standard photon linear accelerator over a 30-year period. Notably, the treatment cost can be reduced to USD 400 to 800 per fraction, substantially lower than that in high-income countries (USD 1000 to 3000 per fraction). CONCLUSION: This study indicates that, in the Indian scenario, all particle therapy models are cost-beneficial and feasible, with large-scale proton therapy being the most suitable. Despite challenges such as limited resources, space, a skilled workforce, referral systems, and patient affordability, it offers substantial benefits. These include the potential to treat many patients and convenient construction and operational costs. An iterative phased implementation strategy can effectively overcome these challenges, paving the way for the successful adoption of particle therapy in India. PLAIN LANGUAGE SUMMARY: In India, eligible patients benefiting from high-precision particle therapy technology projected to rise till 2040. Despite high upfront costs, our study finds the long-term feasibility of all particle therapy models, potentially offering a substantial reduction in treatment cost compared to high-income countries. Despite challenges, India can succeed with an iterative phased approach.

Economic evaluation of vaccination against COVID-19: A systematic review.

Background and Aims: Coronavirus has burdened considerable expenditures on the different health systems. Vaccination programs, the critical solution against pandemic diseases, are known as safe and effective interventions to prevent and control epidemics. We aimed to perform a systematic review to provide economic evidence of the value of different types of vaccines available to combat the Covid-19 to all health policymakers worldwide. Methods: Electronic searches conducted on Medline/PubMed, Cochrane Library, Web of Science, Scopus, Embase, and other economic evaluation databases. Related and published articles searched up to March 2022 by using keywords such as "Vaccination," "Covid-19," "Cost-benefit," "Cost-utility," "Cost-effectiveness," "Economic Assessment," and "Economic evaluation." Followed by choosing the most suitable articles according to inclusion and exclusion criteria, data captured and the results extracted. The quality assessment of the articles performed by the checklist of CHEERS 2022. Finally, 13 articles included in the review. Results: All messenger RNA vaccines were dominant with approximately 70% coverage against no vaccination in the primary vaccination program except in one study that looked at booster effects. From a payer's perspective, a dollar invested in a vaccine would be less profitable than from a societal perspective. Therefore, primary mass vaccination can be considered a cost-effective intervention in primary vaccination to save more lives and produce more positive externalities. However, the cost-benefit ratio for all vaccines increases when statistical lifetime value and global economic and educational disadvantages are considered. Conclusion: The COVID-19 primary vaccination programs in regional outbreaks, from a long-term perspective, will demonstrate substantial cost-effectiveness. It is suggested that due to the positive externalities of vaccination, primary mass vaccination, with the help of COVAX-19TM, could be considered a reliable way to combat viral epidemics compared to the loss of individual lives and economic and educational disturbances around the world.

Economic evaluations of treatment of depressive disorders in adolescents: Protocol for a scoping review.

AIM: Depressive disorders in adolescents are common and impairing. Evidence-based treatments are available; however, at a cost. In the context of the COVID-19 pandemic, we anticipate increased demand for treatment services for adolescents with depression. We also anticipate that economic resources will be strained. Identifying cost-effective strategies to optimally treat depression in adolescents is imperative. This protocol for a scoping review aims to describe the literature with respect to economic evaluations of treatments for depression in adolescents. METHODS: We will conduct a scoping review using established methods and reporting guidelines. MEDLINE, Embase, PsyclNFO, Econlit, and the International HTA Database will be searched from inception to June 13, 2023, with an update closer to time of manuscript submission, while the NHS Economic Evaluation Database archives will be searched from inception to December 2014. Publications that contain economic evaluations, in the context of a clinical trial or a model-based study, testing a treatment of depression in adolescents will be selected for inclusion. Extracted data items will include: economic evaluation perspectives, health outcome variables and costs used in economic evaluations, types of analyses performed, as well as quality of reporting and methodology. RESULT: A narrative synthesis with summary tables will be used to describe our findings. CONCLUSION: Our findings will help identify gaps in the literature with respect to economic analyses for the treatment of depression such that these gaps can be filled with future research. Policy-makers, funders and administrators may also use our findings to inform their decisions around provision of various treatments for depression in adolescents. REGISTRATION: osf.io/5fteb (note that information on this link will be updated upon acceptance for publication based on reviewer comments).

Trigeneration based on the pyrolysis of rural waste in India: Environmental impact, economic feasibility and business model innovation.

Pyrolysis-based waste-to-bioenergy development has the potential to resolve some of the major challenges facing rural communities in India such as poor electrification, household air pollution, and farmland degradation and contamination. Existing understanding and analysis of the economic feasibility and environmental impact of bioenergy deployment in rural areas is limited by parameter uncertainties, and relevant business model innovation following economic evaluation is even scarcer. This paper uses findings from a new field survey of 1200 rural households to estimate the economic feasibility and environmental impact of a pyrolysis-based bioenergy trigeneration development that was designed to tackle these challenges. Based on the survey results, probability distributions were constructed and used to supply input parameters for cost-benefit analysis and life cycle assessment. Monte Carlo simulation was applied to characterise the uncertainties of economic feasibility and environmental impact accounting. It was shown that the global warming potential of the development was 350 kg of CO2-eq per capita per annum. Also, the survey identified a significant mismatch between feedstock prices considered in the literature and prices asked for by the surveyed villagers. The results of the cost-benefit analysis and life cycle assessment were then applied to propose two novel business models inspired by the Business Model Canvas, which had the potential to achieve up to 90 % economic profitability and result in a benefit-cost ratio of 1.35-1.75. This is the first study achieving combined environmental and economic analysis and business model innovation for rural bioenergy production in developing countries.

Changing the liver transplant assessment process from inpatient to a day-case and outpatient approach to reduce inpatient bed utlisation.

The liver transplant assessment process involves a complex set of tests and clinical reviews to determine suitability for liver transplantation. We had an assessment process involving a 3-day inpatient stay and often experienced difficulties admitting patients to the prebooked bed due to a lack of inpatient bed availability.We aimed to change the process from a 3-day and 2-night inpatient stay to a 1-day day-case stay to reduce the demand for inpatient beds.Planning the new assessment process involved negotiations with many department staff to establish prebooked timeslots in 1 day. The improvement project was tested and refined through Plan-Do-Study-Act cycles. The liver transplant assessment team used their established once-a-week meeting to learn what went well and to agree on revisions to the process for further testing. The process involved several adaptations, such as the removal and changing of individual time slots, reinforcement of early notification once patients had finished their tests and scheduling a separate outpatient appointment to provide time for junior doctor clerking and blood tests.The new day-case and outpatient coordinated liver transplant assessment process resulted in a reduction of inpatient hospital bed utilisation from an average of 257-20 inpatient bed days per annum. This reduction in inpatient bed utilisation was maintained for 3 years with a similar level of patient satisfaction. The cost avoidance was calculated at £381.96 per patient, which is a 63% reduction in cost. Assuming an average number of patients being assessed per annum of 110, this would result in an average cost avoidance of £42 016 per annum. The carbon footprint was calculated with an average reduction per patient from 618 kilograms of carbon dioxide equivalent (kgCO2e) to 179 kgCO2e.This project has highlighted how to change a complex inpatient assessment process to an alternative day-case and outpatient approach and could be considered useful learning for other inpatient assessment services, not just liver transplantation.

Designing a Surveillance Sensor Network with Information Clearinghouse for Advanced Air Mobility.

To ensure safe, secure, and efficient advanced air mobility (AAM) operations, an AAM surveillance network is needed to detect and track AAM traffic. Additionally, a cloud-based surveillance data collection, monitoring, and distribution center is needed, where AAM operators and service suppliers, law enforcement agencies, correctional facilities, and municipalities can subscribe to receiving relevant AAM traffic data to plan and monitor AAM operations. In this work, we developed an optimization model to design a surveillance sensor network for AAM that minimizes the total sensor cost while providing full coverage in the desired region of operation, considering terrain types of that region, terrain-based sensor detection probabilities, and meeting the minimum detection probability requirement. Moreover, we present a framework for the low altitude surveillance information clearinghouse (LASIC), connected to the optimized AAM surveillance network for receiving live surveillance feed. Additionally, we conducted a cost-benefit analysis of the AAM surveillance network and LASIC to justify an investment in it. We examine six potential types of AAM sensors and homogeneous and heterogeneous network types. Our analysis reveals the sensor types that are the most profitable options for detecting cooperative and non-cooperative aircraft. According to the findings, heterogeneous networks are more cost-effective than homogeneous sensor networks. Based on the sensitivity analysis, changes in parameters such as subscription fees, the number of subscribers, sensor detection probabilities, and the minimum required detection probability significantly impact the surveillance network design and cost-benefit analysis.

Breaking habits: safety and efficacy of elective electrocardioversion of atrial fibrillation and atrial flutter in the setting of day hospital.

Aim To examine safety and efficiency of electrocardioversion (EC) in elective treatment of atrial fibrillation and atrial flutter in the setting of Day Hospital by determining success rate, frequency of adverse events and possible cost benefit compared to admitting a patient into hospital. Methods This prospective observational cohort study was performed in Day Hospital and in Intensive Care Department of Internal Medicine Clinic, University Clinical Centre Tuzla from January 2019 to December 2022 and included 98 patients with a persistent form of atrial fibrillation (AF) or atrial flutter. The patients who were divided in two groups, 56 hospitalized and 42 patients accessed in Day Hospital. In all patients, medical history, physical examination, electrocardiogram (ECG) and transthoracic echocardiogram (TTE) evaluation was performed in addition to laboratory findings. Electrocardioversion was performed with a monophasic General Electric defibrillator in anterolateral electrode position with up to three repetitive shocks. Results In hospital setting group overall succes rate of electrocardioversion was 85%, with average 2.1 EC attemps, there was with one fatal outcome due to stroke, one case of ventricular fibrillation (VF) due to human error, and 6 minor adverse events; with average cost of was 1408.70 KM (720.23 €) per patient. In Day Hospital setting succes rate was 88%, with average 2 EC attempts, no major adverse events, 8 minor adverse events; and average cost was of 127.23 KM (65.05 €) per patient. Conclusion Performing elective electrocardioversion in Day Hospital setting is as safe as admitting patients into hospital but substantially more cost effective.