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Non-alcoholic steatohepatitis (NASH) and type 2 diabetes (T2D) are both linked to substantial healthcare costs and are often co-occurring. We aim to quantify the incremental cost of NASH and T2D using real-world data. Adults (≥18 years old) with ≥2 diagnosis codes for NASH and/or ≥2 diagnosis codes for T2D between 1/1/2016 and 12/31/2021 and ≥24 months of continuous claims enrollment (study period) were identified in electronic health records or claims in the Veradigm Integrated Dataset. Patients were stratified into 3 cohorts: NASH-only, T2D-only, and NASH + T2D. We calculated annualized costs for the 24-month study period and fit a generalized linear model (excluding the most expensive 1%) that controlled for disease cohort, age, sex, and modified Charlson comorbidity index to estimate the per year all-cause healthcare costs and incremental cost of adding T2D to a NASH diagnosis (or vice versa). We identified 23,111 patients diagnosed with NASH-only, 3,548,786 patients with T2D-only, and 30,339 patients with NASH + T2D. The model-predicted mean costs per year were $7,668 for patients with NASH-only, $11,226 for patients with T2D-only, and $16,812 for patients with NASH + T2D. The incremental increase in costs per year of adding T2D to NASH was 63% (+$4,846), and the incremental increase in costs per year of adding NASH to T2D was 42% (+$4,692). Both NASH and T2D contribute to the high healthcare costs among patients with a dual diagnosis. Results from our analysis indicate that NASH comprises a high portion of total healthcare costs among patients with NASH and T2D. [ABSTRACT FROM AUTHOR]

Objective: To measure the costs of preventive and therapeutic protocols of Photobiomodulation (PBM) for oral mucositis (OM) and their budgetary impact on Brazil’s Ministry of Health (BMH). Material and Methods: A partial economic analysis was performed to estimate the costs using a bottom-up approach from a social perspective. Monetary values were assigned in Brazilian reais (BRL). The costs of the preventive protocol were calculated for five, 30, and 33 consecutive PBM sessions, depending on the antineoplastic treatment instituted. The costs of the therapeutic protocol were calculated for 5 or 10 sessions. The annual financial and budgetary impact was calculated considering the groups of oncologic patients with a higher risk of development of OM, such as those with head and neck and hematological cancer and pediatric patients. Results: The cost of a PBM session was estimated at BRL 23.75. The financial impact of providing one preventive protocol per year for all oncologic patients would be BRL 14,282,680.00, 0.030% of the estimated budget for hospital and outpatient care of the BMH in 2022. The financial and budgetary impacts of providing one treatment for OM for all patients in one year would be BRL 2,225,630.31 (0.005%, most optimistic scenario) and BRL 4,451,355.63 (0.009%, most pessimistic scenario). Conclusion: The budgetary impact of implementing PBM protocols in the Brazilian Healthcare System is small, even in a pessimistic scenario.

Background: This research was conducted with the aim of investigating the effects of green tax on Iran's economy. Methods: This was analytical research using the Nordhaus economic model. The data relating to torques and statistical tests were used to compare actual and model data to determine how well the designed Nordhaus model corresponds to the data on Iran's economy, t and f statistical tests were designed to determine the degree of conformity of the Nordhaus model, and the first and second-order coefficients were used for the variables. Data analysis of the gross domestic product, investment, government spending and oil revenue was used with GAMS software. Results: The values of the simulated and real characteristics did not differ significantly at the 95% confidence level(P-value=0.05), which shows the high compliance of the Nordhaus model with the real data of these variables. According to the Nordhaus model, green tax affects economic welfare. It reduces economic growth in the short term and increases it in the long term. By reducing production, the level of leisure increases and leads to compensate for the reduction in consumption due to reduced production and increased economic welfare. Conclusion: One percentage of increase in the rate of tax on return of capital leads to a reduction in consumption and a reduction in capital. Increasing the rate of tax on return of capital leads to increased tax revenues and helps governments to compensate for pollution costs and improve the quality of the environment.

The use of digital technology by banks and other financial institutions to facilitate financial inclusion is referred to as digital financial inclusion. This fusion of digital finance and traditional banking methods has the potential to impact banks' operational effectiveness. This study uses the panel effects model to examine the link between digital financial inclusion and bank performance in 30 Chinese provinces from 2012 to 2021. This research uses kernel density estimation to examine the spatial-temporal growth patterns of both variables. The mediator variable in examining how digital financial inclusion affects bank performance is risk-taking. Finally, the paper analyses the regional heterogeneity of the impact. It presents the following conclusions: (1) In China, digital financial inclusion and bank performance have constantly increased, with noticeable regional variances in their development levels. This regional inequality has widened gradually since 2018, yet it has not resulted in polarization. (2) The significant positive correlation between digital inclusive finance and banking performance indicates that banking performance tends to increase with the enhancement of digital inclusive finance. (3) Digital financial inclusion impacts bank performance, with risk-taking as a moderator. The spread of digital financial inclusion services enhances banks' willingness to take risks, enhancing overall efficiency. (4) Digital financial inclusion boosts bank performance in the Northwest, South, North, and East regions while lightly inhibiting it in the Central region. Based on the findings, this study makes bank and government suggestions., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This paper uses health economics methods to discuss the cost-effectiveness value of long protocol and antagonist protocol for in vitro fertilisation and embryo transfer (ET) in the Chinese population., Design: Health economic evaluation study., Setting: The data needed to construct the model for this study were derived from published studies and other secondary sources in China., Participants: No patients participated in the study., Measures: The main outcomes were live birth rate (LBR) and cost. From the societal perspective, we considered the direct and indirect costs over the course of the treatment cycles. A cost-effectiveness was measured using the incremental cost-effectiveness ratio and the probability that a protocol has higher net monetary benefit. Sensitivity analysis was carried out to verify the reliability of the simulation results., Results: For the Chinese population, the long protocol resulted in a higher LBR than the antagonist protocol (29.33% vs 20.39%), but at the same time, it was more expensive (￥29 146.26 (US$4333.17) vs ￥23 343.70 (US$3470.51)), in the case of considering only one fresh ET cycle. It was the same when considering subsequent frozen ET (FET) cycles (51.78% vs 42.81%; ￥30 703.02 (US$4564.62) vs ￥24 740.95 (US$3678.24)). The results of most subgroups were consistent with the results of the basic analysis. However, for certain populations, the long protocol was the inferior protocol (less effective and more expensive)., Conclusion: For the Chinese population, when the monetary value per live birth was greater than ￥65 420 (US$9726) and ￥66 400 (US$9872), respectively, considering only one fresh cycle and considering subsequent frozen cycles, the long protocol is the preferred protocol. This threshold also varies for women of different ages and ovarian response capacities. For women in POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) group 2, group 3 and group 4, antagonist protocol is recommended as the preferred protocol. The results of this study need to be verified by further large-scale randomised controlled trials., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Using a multi-product trade model, this study investigates the impact of temperature on firms' diversification in the export market. Using export and meteorological data of Chinese firms from 2000 to 2016, the empirical results confirm an inverted U-shaped relationship, implying that extreme temperatures significantly reduce firms' export product diversification. The analysis shows that extreme temperatures primarily reduce the variety of both new and existing products, with a less robust effect on product exit strategies. General trade firms are more adaptable to extreme temperatures than processing trade firms, and are likely to maintain diversified strategies. Stronger regional financial markets and higher energy consumption increase the adaptability of local firms to extreme temperatures. Firms have not yet adapted to local climatic norms. Furthermore, extreme temperatures also partly inhibit diversification of export destinations and relationships. The results of the study show that as climate change intensifies, leading to more frequent extreme temperatures, firms will face significant hurdles in pursuing diversified development strategies, pointing to increasing challenges ahead., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Zhang, Yao. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Scientific research requires taking risks, as the most cautious approaches are unlikely to lead to the most rapid progress. Yet, much funded scientific research plays it safe and funding agencies bemoan the difficulty of attracting high-risk, high-return research projects. Why don't the incentives for scientific discovery adequately impel researchers toward such projects? Here, we adapt an economic contracting model to explore how the unobservability of risk and effort discourages risky research. The model considers a hidden-action problem, in which the scientific community must reward discoveries in a way that encourages effort and risk-taking while simultaneously protecting researchers' livelihoods against the vicissitudes of scientific chance. Its challenge when doing so is that incentives to motivate effort clash with incentives to motivate risk-taking, because a failed project may be evidence of a risky undertaking but could also be the result of simple sloth. As a result, the incentives needed to encourage effort actively discourage risk-taking. Scientists respond by working on safe projects that generate evidence of effort but that don't move science forward as rapidly as riskier projects would. A social planner who prizes scientific productivity above researchers' well-being could remedy the problem by rewarding major discoveries richly enough to induce high-risk research, but in doing so would expose scientists to a degree of livelihood risk that ultimately leaves them worse off. Because the scientific community is approximately self-governing and constructs its own reward schedule, the incentives that researchers are willing to impose on themselves are inadequate to motivate the scientific risks that would best expedite scientific progress., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gross, Bergstrom. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The purpose of this study is to explore the trends and causes of established and emerging nations' stock market integration with India. The National Stock Exchange (NSE) indices act as a counterweight to international market indices. This study investigates the sustained interest of foreign investors in the Indian stock market in the wake of capital market reforms, as well as whether it moves in tandem with other markets in Asia and the United States. Methods: Our study examined the possibility of cross-country cointegration between the largest economies and indices around the world using multiple financial econometric models, such as Augmented Dickey-Fuller, Unit Root, Correlation, and Johansen Cointegration. Results: The findings of this study significantly support the notion that Indian and international financial markets are highly integrated. Vector error correction model indicates that the Indian market (NSE) is highly cointegrated with the US market (National Association of Securities Dealers Automated Quotations) and increased volatility signifies global contagion. Conclusion: A cursory examination of the data reveals distinct investment and portfolio diversification options for global investors. This could assist regulators in formulating more effective rules regarding price discovery processes., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Ali F et al.)

Physical capital stock is the basic indicator of macroeconomic empirical studies and also an important manifestation of macroeconomic activity capacity. When measuring China's provincial physical capital stock by the perpetual inventory method, the treatment for the depreciation rate and the initial physical capital stock in the existing literature has some defects in reflecting the economic performance. The purpose of this paper is to build the most reliable and reasonable statistical series of China's provincial physical capital stock. We establish a measurement formula in form of the variable depreciation rate and improve the treatment for the depreciation rate and the initial physical capital stock. For the depreciation rate, we measure the benchmark depreciation rate of physical capital and determine the variable depreciation rate according to the economic growth rate, which makes the variable depreciation rate reflect the economic growth. For the initial physical capital stock, we measure the initial physical capital stock according to the capital output ratio, which makes the initial physical capital stock reflect the economic aggregate. Based on these improvements, we measure China's provincial physical capital stock from 1952 to 2022 by the perpetual inventory method. Through analyzing the measurement results, we have a more distinct insight into the temporal and spatial characteristics of China's provincial physical capital stock: The growth rate of physical capital stock at the provincial level has slowed in spite of remaining high; The eastern region is much higher than the central and western regions. According to these two characteristics, it is suggested that policymakers need to improve market mechanisms and adjust investment policies to promote a benign profile of economic growth and a regional optimization of capital formation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang, Ma. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To assess the cost-effectiveness of using cheaper-but-noisier outcome measures, such as a short questionnaire, for large simple clinical trials., Background: To detect associations reliably, trials must avoid bias and random error. To reduce random error, we can increase the size of the trial and increase the accuracy of the outcome measurement process. However, with fixed resources, there is a trade-off between the number of participants a trial can enrol and the amount of information that can be collected on each participant during data collection., Methods: To consider the effect on measurement error of using outcome scales with varying numbers of categories, we define and calculate the variance from categorisation that would be expected from using a category midpoint; define the analytic conditions under which such a measure is cost-effective; use meta-regression to estimate the impact of participant burden, defined as questionnaire length, on response rates; and develop an interactive web-app to allow researchers to explore the cost-effectiveness of using such a measure under plausible assumptions., Results: An outcome scale with only a few categories greatly reduced the variance of non-measurement. For example, a scale with five categories reduced the variance of non-measurement by 96% for a uniform distribution. We show that a simple measure will be more cost-effective than a gold-standard measure if the relative increase in variance due to using it is less than the relative increase in cost from the gold standard, assuming it does not introduce bias in the measurement. We found an inverse power law relationship between participant burden and response rates such that a doubling the burden on participants reduces the response rate by around one third. Finally, we created an interactive web-app ( https://benjiwoolf.shinyapps.io/cheapbutnoisymeasures/ ) to allow exploration of when using a cheap-but-noisy measure will be more cost-effective using realistic parameters., Conclusion: Cheaper-but-noisier questionnaires containing just a few questions can be a cost-effective way of maximising power. However, their use requires a judgement on the trade-off between the potential increase in risk of information bias and the reduction in the potential of selection bias due to the expected higher response rates., (© 2024. The Author(s).)

Fluctuations in the financial market are influenced by various driving forces and numerous factors. Traditional financial research aims to identify the factors influencing stock prices, and existing works construct a common neural network learning framework that learns temporal dependency using a fixed time window of historical information, such as RNN and LSTM models. However, these models only consider the short-term and point-to-point relationships within stock series. The financial market is a complex and dynamic system with many unobservable temporal patterns. Therefore, we propose an adaptive period-aggregation model called the Latent Period-Aggregated Stock Transformer (LPAST). The model integrates a variational autoencoder (VAE) with a period-to-period attention mechanism for multistep prediction in the financial time series. Additionally, we introduce a self-correlation learning method and routing mechanism to handle complex multi-period aggregations and information distribution. Main contributions include proposing a novel period-aggregation representation scheme, introducing a new attention mechanism, and validating the model's superiority in long-horizon prediction tasks. The LPAST model demonstrates its potential and effectiveness in financial market prediction, highlighting its relevance in financial research and predictive analytics., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Tang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In the digital era, digital economy has a far-reaching impact on the collaborative agglomeration of manufacturing and service industries. This research aims to examine the economic relationship between digital economy and industrial collaborative agglomeration. Based on a panel data set of 286 Chinese cities, this research employs Tobit model, moderating effect model, and mediating effect model to conduct data analysis. It is found that digital economy has a nonlinear relationship with industrial collaborative agglomeration, and this relationship is a U-shape. Moderating effect analysis reveals that government intervention significantly regulates the role of digital economy in industrial collaborative agglomeration. Mediating effect analysis indicates that digital economy promotes industrial collaborative agglomeration through entrepreneurial activity. Heterogeneity analysis shows that the facilitating effect of digital economy on collaborative agglomeration in high-end industries comes earlier than in middle- and low-end industries. Moreover, this research finds that digital economy plays a significant role in industrial collaborative agglomeration in central and western regions of China but not in the eastern region. To enhance the impact of digital economy on industrial collaborative agglomeration, it is crucial to strengthen the engagement of the government and ensure the availability of digital technology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Small and medium-sized enterprises (SMEs) were an important part of China's economy, but they faced challenges to growth due to financing difficulties. Government subsidies are considered as a potential way to address this problem. This study aims to assess the effectiveness of the Chinese government's subsidy program aimed at improving the accessibility of financing for SMEs. We analyze a comprehensive dataset of Chinese firms' subsidy programs from 2011 to 2020. We classify subsidies into unconditional and conditional categories and use fixed-effects regression models to control for the effects of time and between-group variation to more accurately assess the effectiveness of government subsidies. In addition, we use a PSM-DID model to reduce the effect of selectivity bias to more accurately estimate the causal effect of subsidies on financing strategies. We also use a mediated effects model to help understand the mechanisms by which different types of subsidies affect financing strategies. The results show that government subsidies can significantly improve SMEs' financing ability, but different types of subsidies produce subtle differences. Conditional subsidies support debt financing mainly through incentives, while unconditional subsidies help SMEs improve their equity financing ability through information effects. Furthermore, we find that over-reliance on a single subsidy type may reduce its effectiveness, suggesting a complex relationship between government intervention and SME financing. Thus, well-designed policies are crucial for promoting SMEs and fostering economic growth., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Innovative products entering the market will cause dynamic changes in market demand, and consumers' purchase regret and their return behavior make the market environment more and more complex, which in turn affects the dynamic decision-making in the supply chain. In this paper, under the situation of discrete decision time, combining with the objective reality, we make discrete modification to the classical Bass diffusion model (Bass model), construct a manufacturer-led, retailer-followed supply chain differential game model, analyze the optimal decision-making of the manufacturer and the retailer by combining with the theory of discrete optimal control, and then verify the conclusions by numerical simulation. The results show that: when retailers purchase directly from the manufacturer and sell in the market, the optimal pricing of the innovative product can make the supply chain as a whole, realizing Pareto optimality; consumer's purchase regret will increase the amount of returns, which will lead to the decrease of product sales and the profits of the manufacturer and the retailer; when the innovative product accounts for a different share of the market, the impact of purchase regret on the wholesale price and the retail price are also different. Therefore, manufacturers need to have an extensive comprehension of the market to minimize the negative effects of consumer regret and returns, and to formulate a reasonable pricing strategy for their products to gain as much profit as possible., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objective: In Italy, the management of metastatic non-small cell lung cancer and melanoma leads to significant healthcare challenges, necessitating cost-effective treatment strategies and offering valuable insights for healthcare policymakers and stakeholders. This study was designed to assess the costs, quality-adjusted life-years (QALYs) and disability-adjusted life-years (DALYs) associated with the health and economic outcomes of (1) pembrolizumab-combined chemotherapy administered as a first-line treatment for metastatic non-squamous and squamous non-small cell lung cancer (NSCLC) where the tumour presents with a programmed death-ligand 1 expression level < 50% and of (2) adjuvant pembrolizumab treatment for stage III melanoma., Methods: Three cost-effectiveness models developed by MSD were investigated for each treatment indication. A unique model was built to assess the overall effect of pembrolizumab versus chemotherapy or watchful waiting in patients with lung cancer or melanoma, respectively. Theoretical cohorts of patients with metastatic squamous and non-squamous NSCLC were followed over time using a partitioned survival model with weekly cycles. A weekly cycle Markov model was employed for melanoma. The analysis was conducted from the Italian National Health Service perspective, considering a time horizon of 40 years (lifetime). A single closed cohort of treatable patients was followed over time for each indication (4000, 7000 and 900 for NSCLC squamous, non-squamous and melanoma, respectively). The costs evaluated included those for adverse drug events, non-drug disease management, subsequent treatment and terminal care. Drug acquisition and administration costs were excluded., Results: For each treatment indication assessed, pembrolizumab produced downstream direct cost offsets (- €122,498,568, - €133,369,076 and - €32,993,242 for NSCLC squamous, non-squamous and melanoma indications, respectively), increased quality of life (+2088, +5317 and +2307 QALYs for NSCLC squamous, non-squamous and melanoma indications, respectively) and reduced disability (- 2658, - 7202 and - 3029 DALYs for NSCLC squamous, non-squamous and melanoma indications, respectively). Across indications, the total cost offsets of pembrolizumab were - €288,860,885, with 9712 QALYs gained and 12,889 DALYs avoided., Conclusions: The analysis demonstrated that, compared with chemotherapy, pembrolizumab is more cost effective in Italy as a first-line treatment in patients with metastatic squamous or non-squamous NSCLC and, if compared with watchful waiting, as adjuvant treatment in patients with stage III melanoma. The present analysis suggested that pembrolizumab use could lead to important health benefits for patients while offsetting a portion of cancer care costs., (© 2024. Merck & Co., Inc., Rahway, NJ, USA and its affiliates.)

Background: One in 7 adults have chronic kidney disease (CKD), which is associated with high morbidity and mortality and substantial health care costs, especially in more advanced disease. Our data from a US commercial payer show rising per-member-per-year costs for renal and cardiac complications associated with CKD., Objective: To predict the clinical and economic impact of treatment with or without dapagliflozin from the perspective of a US commercial payer using a cost-offset model (COM)., Methods: The COM used real-world cost and member count data from a US employer-sponsored commercial payer and results of the double-blind, randomized, phase 3 Dapagliflozin and Prevention of Adverse Outcomes in CKD clinical trial (NCT03036150) to predict the incidence of clinical events, including a greater than or equal to 50% decline in estimated glomerular filtration rate (eGFR), end-stage kidney disease, and hospitalization for heart failure, and their associated costs over a 3-year period. The COM compared a hypothetical scenario of the experience with or without dapagliflozin in members with CKD stages 2-4, aged younger than 65 years., Results: In the simulated populations of 130 members, the COM projected 9 events of a greater than or equal to 50% decline in estimated glomerular filtration rate for the experience with dapagliflozin vs 15 events for the experience without dapagliflozin (6 fewer events; number needed to treat [NNT] = 20, amounting to estimated cumulative cost offsets of $0.57 million [M] over a 3-year period). The COM projected similar results for end-stage kidney disease (8 events with dapagliflozin vs 14 events without dapagliflozin; NNT = 24, amounting to $1.92 M in cumulative cost offsets) and for hospitalization for heart failure (13 events with dapagliflozin vs 33 events without dapagliflozin; NNT = 7, amounting to $0.79 M in cumulative cost offsets). These projections translated to total mean, cumulative cost offsets of $3.89 M for all clinical events evaluated over the 3-year period (36.6% reduction with dapagliflozin vs without dapagliflozin), and net mean, cumulative cost offsets of $2.58 M over the 3-year period (24.2% reduction with dapagliflozin vs without dapagliflozin) after factoring in a discounted wholesale acquisition cost for dapagliflozin expenditure ($1.31 M over 3 years). Thus, the net mean, cumulative cost offsets were $19,843 per member over 3 years, representing a 197% return on investment for dapagliflozin expenditure., Conclusions: Results of our COM suggest that dapagliflozin can reduce clinical events and their associated costs over a 3-year period when compared with a scenario without dapagliflozin. Cost offsets increased with each year, indicating that US commercial payers can substantially reduce costs associated with CKD morbidity and mortality.

In the last few decades, developers of new drugs, biologics, and devices have increasingly leveraged digital health technologies (DHTs) to assess clinical trial digital endpoints. To our knowledge, a comprehensive assessment of the financial net benefits of digital endpoints in clinical trials has not been conducted. We obtained data from the Digital Medicine Society (DiMe) Library of Digital Endpoints and the US clinical trials registry, ClinicalTrials.gov. The benefit metrics are changes in trial phase duration and enrollment associated with the use of digital endpoints. The cost metric was obtained from an industry survey of the costs of including digital endpoints in clinical trials. We developed an expected net present value (eNPV) model of the cash flows for new drug development and commercialization to assess financial value. The value measure is the increment in eNPV that occurs when digital endpoints are employed. We also calculated a return on investment (ROI) as the ratio of the estimated increment in eNPV to the mean digital endpoint implementation cost. For phase II trials, the increase in eNPV varied from $2.2 million to $3.3 million, with ROIs between 32% and 48% per indication. The net benefits were substantially higher for phase III trials, with the increase in eNPV varying from $27 million to $40 million, with ROIs that were four to six times the investment. The use of digital endpoints in clinical trials can provide substantial extra value to sponsors developing new drugs, with high ROIs., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Heart failure (HF) is among the leading causes of death in the United States. Further, patients hospitalized because of HF with comorbid diabetes mellitus (DM) are at a significantly increased risk of death and rehospitalization. Results from the SOLOIST-WHF trial show that sotagliflozin lowered rates of readmission among hospitalized patients with HF and comorbid DM. However, it is unclear what the economic impact of the use of sotagliflozin would be on hospitals and health systems, particularly in an age where provider reimbursement is increasingly tied to value., Objective: To quantify the 1-year financial impact on US provider health systems of adopting sotagliflozin relative to standard of care (SoC) across different alternative payment models., Methods: This study created a 3-part decision tree model to quantify the financial impact of using sotagliflozin to treat patients hospitalized with HF in a US hospital setting. The model first estimated the clinical and economic outcomes of health systems with current SoC (no sotagliflozin) to treat US patients hospitalized for HF with comorbid DM. Then, using the results from the SOLOIST trial, the changes in clinical and economic outcomes with sotagliflozin adoption were modeled. Finally, the differences in health care utilization between sotagliflozin and SoC arms were translated to differences in health system reimbursement in the context of 3 common alternative payment models (APMs) in addition to the baseline fee-for-service (FFS) model: FFS with the Hospital Readmissions Reduction Program, the Bundled Payments for Care Improvement-Advanced program, and Accountable Care Organizations., Results: A typical community hospital would have 83.4 patients per year on average with an index HF hospitalization with comorbid DM. The model predicted that sotagliflozin would reduce the probability of hospitalization, emergency department visits, and deaths by 29.3%, 38.5%, and 17.8%, respectively, compared with SoC. For hospitals not participating in APM programs, sotagliflozin resulted in a net loss of $92.94 per person ($7,754 per health system). Conversely, when accounting for provider health system participation in APMs, sotagliflozin adoption increased financial returns by $4,720 per person ($305,604 per health system) under the Hospital Readmissions Reduction Program, $1,200 per person ($100,106 per health system) for the Bundled Payments for Care Improvement-Advanced program, and $1,078 per person ($31,029 per health system) for Accountable Care Organizations. Based on the national average composition of APM reimbursement, sotagliflozin adoption resulted in a $1,576 increase in margin per patient with HF ($105,454 per health system)., Conclusions: Although sotagliflozin adoption reduced health system revenue in an FFS payment model, it led to a net positive financial impact after accounting for APM bonus payments.

Aim: The objective of this study was to compare adverse event (AE) management costs for fruquintinib, regorafenib, trifluridine/tipiracil (T/T) and trifluridine/tipiracil+bevacizumab (T/T+bev) for patients with metastatic colorectal cancer (mCRC) previously treated with at least two prior lines of therapy from the US commercial and Medicare payer perspectives. Materials & methods: A cost-consequence model was developed to calculate the per-patient and per-patient-per-month (PPPM) AE costs using rates of grade 3/4 AEs with incidence ≥5% in clinical trials, event-specific management costs and duration treatment. Anchored comparisons of AE costs were calculated using a difference-in-differences approach with best supportive care (BSC) as a common reference. AE rates and treatment duration were obtained from clinical trials: FRESCO and FRESCO-2 (fruquintinib), RECOURSE (T/T), CORRECT (regorafenib) and SUNLIGHT (T/T, T/T+bev). AE management costs for the commercial and Medicare perspectives were obtained from publicly available sources. Results: From the commercial perspective, the AE costs (presented as per-patient, PPPM) were: $4015, $1091 for fruquintinib (FRESCO); $4253, $1390 for fruquintinib (FRESCO-2); $17,110, $11,104 for T/T (RECOURSE); $9851, $4691 for T/T (SUNLIGHT); $8199, $4823 for regorafenib; and $11,620, $2324 for T/T+bev. These results were consistent in anchored comparisons: the difference-in-difference for fruquintinib based on FRESCO was -$1929 versus regorafenib and -$11,427 versus T/T; for fruquintinib based on FRESCO-2 was -$2257 versus regorafenib and -$11,756 versus T/T. Across all analyses, results were consistent from the Medicare perspective. Conclusion: Fruquintinib was associated with lower AE management costs compared with regorafenib, T/T and T/T+bev for patients with previously treated mCRC. This evidence has direct implications for treatment, formulary and pathways decision-making in this patient population.

In this update, we discuss recent US FDA guidance offering more specific guidelines on appropriate study design and analysis to support causal inference for non-interventional studies and the launch of the European Medicines Agency (EMA) and the Heads of Medicines Agencies (HMA) public electronic catalogues. We also highlight an article recommending assessing data quality and suitability prior to protocol finalization and a Journal of the American Medical Association -endorsed framework for using causal language when publishing real-world evidence studies. Finally, we explore the potential of large language models to automate the development of health economic models.

Purpose: The health and economic consequences of artificial intelligence (AI) systems for mechanically ventilated intensive care unit patients often remain unstudied. Early health technology assessments (HTA) can examine the potential impact of AI systems by using available data and simulations. Therefore, we developed a generic health-economic model suitable for early HTA of AI systems for mechanically ventilated patients., Materials and Methods: Our generic health-economic model simulates mechanically ventilated patients from their hospitalisation until their death. The model simulates two scenarios, care as usual and care with the AI system, and compares these scenarios to estimate their cost-effectiveness., Results: The generic health-economic model we developed is suitable for estimating the cost-effectiveness of various AI systems. By varying input parameters and assumptions, the model can examine the cost-effectiveness of AI systems across a wide range of different clinical settings., Conclusions: Using the proposed generic health-economic model, investors and innovators can easily assess whether implementing a certain AI system is likely to be cost-effective before an exact clinical impact is determined. The results of the early HTA can aid investors and innovators in deployment of AI systems by supporting development decisions, informing value-based pricing, clinical trial design, and selection of target patient groups., Competing Interests: Declaration of competing interest Authors LRZ, JK, SvdP, ADIvA and BF have no competing interests to declare that are relevant to the content of this article. MJP reports grants and personal fees from various pharmaceutical industries, all outside the submitted work. He holds stocks in Pharmacoeconomics Advice Groningen (PAG Ltd.; Groningen, Netherlands) and Health-Ecore Ltd. (Zeist/Groningen, Netherlands) and is advisor to Asc Academics (Groningen/Utrecht, Netherlands), all pharmacoeconomic consultancy companies. The Department of Anaesthesiology, Intensive Care Medicine & Pain Therapy of the University Hospital Frankfurt, Goethe University received support from B. Braun Melsungen, CSL Behring, Fresenius Kabi, and Vifor Pharma for the implementation of Frankfurt‘s Patient Blood Management program. KZ has received honoraria for participation in advisory board meetings for Haemonetics and Vifor and received speaker fees from CSL Behring, Masimo, Pharmacosmos, Boston Scientific, Salus, iSEP, Edwards and GE Healthcare. He is the Principal Investigator of the EU-Horizon 2020 project ENVISION (Intelligent plug-and-play digital tool for real-time surveillance of COVID-19 patients and smart decision-making in Intensive Care Units) and Horizon Europe 2021 project COVend (Biomarker and AI-supported FX06 therapy to prevent progression from mild and moderate to severe stages of COVID-19)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To illustrate the financial consequences of implementing different managed entry agreements (managed entry agreements for the Dutch healthcare system for autologous gene therapy atidarsagene autotemcel [Libmeldy]), while also providing a first systematic guidance on how to construct managed entry agreements to aid future reimbursement decision making and create patient access to high-cost, one-off potentially curative therapies., Methods: Three payment models were compared: (1) an arbitrary 60% price discount, (2) an outcome-based spread payment with discounts, and (3) an outcome-based spread payment linked to a willingness to pay model with discounts. Financial consequences were estimated for full responders (A), patients responding according to the predicted clinical pathway presented in health technology assessment reports (B), and unstable responders (C). The associated costs for an average patient during the time frame of the payment agreement, the total budget impact, and associated benefits expressed in quality-adjusted life-years of the patient population were calculated., Results: When patients responded according to the predicted clinical pathway presented in health technology assessment reports (scenario B), implementing outcome-based reimbursement models (models 2 and 3) had lower associated budget impacts while gaining similar benefits compared with the discount (scenario 1, €8.9 million to €6.6 million vs €9.2 million). In the case of unstable responders (scenario C), costs for payers are lower in the outcome-based scenarios (€4.1 million and €3.0 million, scenario 2C and 3C, respectively) compared with implementing the discount (€9.2 million, scenario 1C)., Conclusions: Outcome-based models can mitigate the financial risk of reimbursing atidarsagene autotemcel. This can be considerably beneficial over simple discounts when clinical performance was similar to or worse than predicted., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section. The views expressed in this article are the personal views of the authors. They may not be understood or quoted as being made on behalf of or reflecting the position of the agencies or organizations with which the authors are affiliated., (Copyright © 2024. Published by Elsevier Inc.)

Background: The disparity between the demand for and supply of kidney transplants has resulted in prolonged waiting times for patients with kidney failure. A potential approach to address this shortage is to consider kidneys from donors with a history of common cancers, such as breast, prostate, and colorectal cancers., Methods: We used a patient-level Markov model to evaluate the outcomes of accepting kidneys from deceased donors with a perceived history of breast, prostate, or colorectal cancer characterized by minimal to intermediate transmission risk. Data from the Australian transplant registry were used in this analysis. The study compared the costs and quality-adjusted life years (QALYs) from the perspective of the Australian healthcare system between the proposed practice of accepting these donors and the conservative practice of declining them. The model simulated outcomes for 1500 individuals waitlisted for a deceased donor kidney transplant for a 25-y horizon., Results: Under the proposed practice, when an additional 15 donors with minimal to intermediate cancer transmission risk were accepted, QALY gains ranged from 7.32 to 20.12. This translates to an approximate increase of 7 to 20 additional years of perfect health. The shift in practice also led to substantial cost savings, ranging between $1.06 and $2.3 million., Conclusions: The proposed practice of accepting kidneys from deceased donors with a history of common cancers with minimal to intermediate transmission risk offers a promising solution to bridge the gap between demand and supply. This approach likely results in QALY gains for recipients and significant cost savings for the health system., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

We are developing an economic model to explore multiple topics in Australian youth mental health policy. To help make that model more readily transferable to other jurisdictions, we developed a software framework for authoring modular computational health economic models (CHEMs) (the software files that implement health economic models). We specified framework user requirements for: a simple programming syntax; a template CHEM module; tools for authoring new CHEM modules; search tools for finding existing CHEM modules; tools for supplying CHEM modules with data; reproducible analysis and reporting tools; and tools to help maintain a CHEM project website. We implemented the framework as six development version code libraries in the programming language R that integrate with online services for software development and research data archiving. We used the framework to author five development version R libraries of CHEM modules focussed on utility mapping in youth mental health. These modules provide tools for variable validation, dataset description, multi-attribute instrument scoring, construction of mapping models, reporting of mapping studies and making out of sample predictions. We assessed these CHEM module libraries as mostly meeting transparency, reusability and updatability criteria that we have previously developed, but requiring more detailed documentation and unit testing of individual modules. Our software framework has potential value as a prototype for future tools to support the development of transferable CHEMs.Code: Visit https://www.ready4-dev.com for more information about how to find, install and apply the prototype software framework., (© 2024. The Author(s).)

Background: Etranacogene dezaparvovec is a recently approved gene therapy for people with hemophilia B (PwHB). Current standard of care is prophylaxis with factor IX (FIX) to prevent bleeding. Etranacogene dezaparvovec increases blood FIX levels such that FIX prophylaxis could be eliminated., Objective: To estimate the budgetary impact of etranacogene dezaparvovec adoption and utilization in a commercial health plan of the United States., Methods: A budget impact model was developed to evaluate the introduction of etranacogene dezaparvovec to treat severe or moderately severe hemophilia B. The model considered a hypothetical 1-million-member plan over a 5-year horizon. FIX therapy prophylaxis use was estimated based on a weighted average of relevant brands using US market share data. A scenario of etranacogene dezaparvovec adoption/utilization was compared with one without etranacogene dezaparvovec utilization. Two etranacogene dezaparvovec uptake (market share growth) analyses were performed: one with gradual uptake and alternatively assuming all eligible PwHB received etranacogene dezaparvovec in year 1. The one-time cost of etranacogene dezaparvovec was assumed to be $3.5 million. Other costs (FIX prophylaxis, disease monitoring, bleed management, and adverse events) were estimated from published literature. All costs were in 2022 US dollars. Bleed and adverse event rates were sourced from the HOPE-B trial comparing etranacogene dezaparvovec to previous FIX therapy prophylaxis. The model estimated annual and per-member per-month costs over 5 years. Secondary analyses were performed considering a 10-year horizon., Results: In the 1-million-member health plan, an estimated 1.8 PwHB were eligible for treatment with etranacogene dezaparvovec. Gradual uptake of etranacogene dezaparvovec resulted in cumulative 5-year budget impact of $848,509 compared with a scenario without etranacogene dezaparvovec. In years 1-5, the incremental annual and per-member per-month costs ranged from $79,824 to $271,435 and from $0.007 to $0.023, respectively. In the alternative uptake analysis, etranacogene dezaparvovec became cost saving annually beginning in year 2 and cumulatively beginning in year 5, for a 5-year savings of $754,844. Secondary analyses over 10 years found both uptake analyses cost saving. Other scenarios considered did not affect results substantially., Conclusions: Introducing etranacogene dezaparvovec as treatment for PwHB would have a modest budget increase within 5 years after treatment but may become cost saving if all eligible PwHB were treated in year 1. Initiating PwHB on etranacogene dezaparvovec sooner may produce greater overall savings and earlier annual savings. Etranacogene dezaparvovec is a treatment option that may provide overall cost savings for US commercial health plans, which would increase as the plan size increases.

Objectives: Health economic (HE) models are often considered as "black boxes" because they are not publicly available and lack transparency, which prevents independent scrutiny of HE models. Additionally, validation efforts and validation status of HE models are not systematically reported. Methods to validate HE models in absence of their full underlying code are therefore urgently needed to improve health policy making. This study aimed to develop and test a generic dashboard to systematically explore the workings of HE models and validate their model parameters and outcomes., Methods: The Probabilistic Analysis Check dashBOARD (PACBOARD) was developed using insights from literature, health economists, and a data scientist. Functionalities of PACBOARD are (1) exploring and validating model parameters and outcomes using standardized validation tests and interactive plots, (2) visualizing and investigating the relationship between model parameters and outcomes using metamodeling, and (3) predicting HE outcomes using the fitted metamodel. To test PACBOARD, 2 mock HE models were developed, and errors were introduced in these models, eg, negative costs inputs, utility values exceeding 1. PACBOARD metamodeling predictions of incremental net monetary benefit were validated against the original model's outcomes., Results: PACBOARD automatically identified all errors introduced in the erroneous HE models. Metamodel predictions were accurate compared with the original model outcomes., Conclusions: PACBOARD is a unique dashboard aiming at improving the feasibility and transparency of validation efforts of HE models. PACBOARD allows users to explore the working of HE models using metamodeling based on HE models' parameters and outcomes., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Background: Initiatives in perioperative care warrant robust cost-effectiveness analysis in a cost-constrained era when high-value care is a priority. A model of anesthesia-led early high-acuity postoperative care, advanced recovery room care (ARRC), has shown benefit in terms of hospital and patient outcomes, but its cost-effectiveness has not yet been formally determined., Methods: Data from a previously published single-center prospective cohort study of ARRC in medium-risk patients were used to generate a Markov model, which described patient transition between care locations, each with different characteristics and costs. The incremental cost-effectiveness ratio (ICER), using days at home (DAH) and hospital costs, was calculated for ARRC compared to usual ward care using deterministic and probabilistic sensitivity analysis., Results: The Markov model accurately described patient disposition after surgery. For each patient, ARRC provided 4.3 more DAH within the first 90 days after surgery and decreased overall hospital costs by $1081 per patient. Probabilistic sensitivity analysis revealed that ARRC had a 99.3% probability of increased DAH and a 77.4% probability that ARRC was dominant from the perspective of the hospital, with improved outcomes and decreased costs., Conclusions: Early high-acuity care for approximately 24 hours after surgery in medium-risk patients provides highly cost-effective improvements in outcomes when compared to usual ward care., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2023 International Anesthesia Research Society.)

Objectives: The results of a recent single-arm trial (ZUMA-5) of axicabtagene ciloleucel (axi-cel) for relapsed/refractory (r/r) follicular lymphoma (FL) demonstrated high rates of durable response and tolerable toxicity among treated patients. To quantify the value of axi-cel compared with standard of care (SOC) to manage r/r FL patients who have had at least 2 prior lines of systemic therapy (3L+), a cost-effectiveness model was developed from a US third-party payer perspective., Methods: A 3-state partitioned-survival cost-effectiveness model was developed with a lifetime horizon. Patient-level analyses of the 36-month ZUMA-5 (axi-cel) and SCHOLAR-5 (SOC) studies were used to extrapolate progression-free and overall survivals. After 5 years of survival, an estimated 40% of the modeled population was assumed to experience long-term remission based on literature. Results include the incremental cost-effectiveness ratio (ICER) measured as incremental cost per quality-adjusted life year (QALY) gained. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analyses were performed. All outcomes were discounted 3% per year., Results: Axi-cel led to an increase of 4.28 life-years, 3.64 QALYs, and a total cost increase of $321 192 relative to SOC, resulting in an ICER of $88 300 per QALY. Across all parameters varied in the one-way sensitivity analysis, the ICER varied between $133 030 and $67 277. In the probabilistic sensitivity analysis, axi-cel had a 99% probability of being cost-effective across 5000 iterations using a $150 000 willingness-to-pay threshold., Conclusions: Given the robustness of the model results and sensitivity analyses, axi-cel is expected to be a cost-effective treatment in 3L+ r/r FL., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: The optimal adjuvant therapy (antiestrogen therapy [ET] + radiation therapy or ET alone, or in some reports radiation therapy alone) in older women with early-stage breast cancer has been highly debated. However, granular details on the role of insurance in the out-of-pocket cost for patients receiving ET with or without radiation therapy are lacking. This project disaggregates out-of-pocket costs by insurance plans to increase treatment cost transparency., Methods and Materials: Several radiation therapy schedules are accepted standards as per the National Comprehensive Cancer Network guidelines. For our financial estimate model, we used the 5-fraction and 15-fraction radiation therapy and ET prescribed over a 5-year duration. The total aggregate out-of-pocket costs were determined from the sum of treatment costs, deductibles, and copays/coinsurance based on Medicaid, Original Medicare, Medigap Plan G, and Medicare Part D Rx plans. The model assumes a Medicare- and/or Medicaid-eligible patient ≥70 years of age with node-negative, early-stage estrogen-receptor-positive breast cancer. Patient out-of-pocket costs were estimated from publicly available insurance data from plan-specific benefit coverage materials using a 5-year time horizon., Results: Original Medicare beneficiaries face a total out-of-pocket treatment charge of $2738.52 for ET alone, $2221.26 for 5-fraction radiation therapy alone, $2573.92 for 15-fraction radiation therapy alone, $3361.26 for combined ET+ 5-fraction radiation therapy, and $3713.92 for combined ET + 15-fraction radiation therapy. Medigap Plan G beneficiaries have an out-of-pocket charge of $1130.00 with radiation therapy alone and face an out-of-pocket of $2270.00 for ET alone and combined ET+ radiation therapy. For Medicaid beneficiaries, all treatments approved by Medicaid are covered without limit, resulting in no out-of-pocket expense for either adjuvant treatment option., Conclusions: This model (based on actual cost estimates per insurance plan rather than claims data), by estimating expenses within Medicare and Medicaid plans, provides a level of transparency to patient cost. With knowledge of the costs borne by patients themselves, treatment decisions informed by patients' individual priorities and preferences may be further enhanced., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To quantify the economic investment required to increase bariatric surgery (BaS) capacity in National Health Service (NHS) England considering the growing obesity prevalence and low provision of BaS in England despite its high clinical effectiveness., Design: Data were included for the patients with obesity who were eligible for BaS. We used a decision-tree approach including four distinct steps of the patient pathway to capture all associated resource use. We estimated total costs according to the current capacity (current scenario) and three BaS scaling up strategies over a time horizon of 20 years (projected scenario): maximising NHS capacity (strategy 1), maximising NHS and private sector capacity (strategy 2) and adding infrastructure to NHS capacity to cover the entire prevalent and incident obesity populations (strategy 3)., Setting: BaS centres based in NHS and private sector hospitals in England., Main Outcome Measures: Number of BaS procedures (including revision surgery), cost (GBP) and resource utilisation over 20 years., Results: At current capacity, the number of BaS procedures and the total cost over 20 years were estimated to be 140 220 and £1.4 billion, respectively. For strategy 1, these values were projected to increase to 157 760 and £1.7 billion, respectively. For strategy 2, the values were projected to increase to 232 760 and £2.5 billion, respectively. Strategy 3 showed the highest increase to 564 784 and £6.4 billion, respectively, with an additional 4081 personnel and 49 facilities required over 20 years., Conclusions: The expansion of BaS capacity in England beyond a small proportion of the eligible population will likely be challenging given the significant upfront economic investment and additional requirement of personnel and infrastructure., Competing Interests: Competing interests: JB-K and AT are current employees of Novo Nordisk and hold shares in the company. DJP has been funded by the Royal College of Surgeons of England. He receives consulting fees from Johnson & Johnson, GSK, Pfizer and Novo Nordisk and payments for lectures, presentations and educational events from Johnson & Johnson, Medtronic and Novo Nordisk. KM has been paid honoraria for educational activities related to bariatric surgery by various corporate organisations and NHS Trusts. RW has no competing interests to declare. YL, YS and IG are employees of IQVIA and have received consulting fees from Novo Nordisk., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In countries where malaria is endemic, the use of rapid diagnostic tests(RDTs) has become routine, especially in rural settings. Such regions are characterised by often having other co-endemic infectious diseases, at high levels of prevalence., Aim: To illustrate the potential added-value of "sentinel" screening for patients presenting for a routine diagnostic test for malaria, at healthcare facilities in Uganda., Methods: We developed an economic model by combining two decision trees, one for malaria and a second for the co-endemic disease schistosomiasis. The integrated model was designed to inform policy strategies for the co-endemic disease in addition to malaria (i.e., whether to test opportunistically for schistosomiasis or use mass drug administration(MDA) as per usual practice).We performed the analysis on three comparators varying testing accuracy and costs., Results: Sentinel screening can provide added value to the testing of patients compared with the status quo: when schistosomiasis prevalence is high then MDA is preferential; if low prevalence, treating no one is preferred. If the disease has average levels of prevalence, then a strategy involving testing is preferred. Prevalence thresholds driving the dominant strategy are dependent upon the model parameters, which are highly context specific. At average levels of prevalence for schistosomiasis and malaria for Uganda, adding a sentinel screening was cost-effective when the accuracy of test was higher than current diagnostics and when economies of scope were generated(Expected value clinical Information = 0.65$ per DALY averted, 137.91$ per correct diagnoses).Protocols using diagnostics with current accuracy levels were preferred only for levels of MDA coverage below 75%., Conclusion: The importance of the epidemiological setting is crucial in determining the best cost-effective strategy for detecting endemic disease. Economies of scope can make sentinel screenings cost-effective strategies in specific contexts. Blanket thresholds recommended for MDA may not always be the preferred option for endemic diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Manca et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The global economic situation is in a downturn, and the upgrading of manufacturing structure is a necessary transformation path for the manufacturing industry to achieve high-speed and stable development. The article analyzes the theoretical mechanism of the digital economy affecting the upgrading of manufacturing structure through the endogenous economic growth model, constructs a three-stage mediation effect model, and empirically researches the path of the digital economy affecting the upgrading of manufacturing structure in the Pearl River Delta. The study finds that the digital economy has a significant positive promoting effect on the upgrading of manufacturing structure. In terms of the influencing mechanism, the enhancement of the level of independent innovation and the advancement of the human capital structure are the important paths of the digital economy in promoting the upgrading of manufacturing structure. Among them, the mediating effect is 17.5% for the level of independent innovation and 17.4% for the level of the advancement of the human capital structure. The results of the study also found that the upgrading of manufacturing structure cannot be separated from government support, and the influence of government support on t the upgrading of manufacturing structure reaches 44.9%, and government deployment and control is conducive to accelerating the process of advanced manufacturing structure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen, Zhou. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To quantify prevalence, harms, and NHS costs in England of problematic oral non-steroidal anti-inflammatory drug (NSAID) prescribing in high risk groups., Design: Population based cohort and economic modelling study., Setting: Economic models estimating patient harm associated with NSAID specific hazardous prescribing events, and cost to the English NHS, over a 10 year period, were combined with trends of hazardous prescribing event to estimate national levels of patient harm and NHS costs., Participants: Eligible participants were prescribed oral NSAIDs and were in five high risk groups: older adults (≥65 years) with no gastroprotection; people who concurrently took oral anticoagulants; or those with heart failure, chronic kidney disease, or a history of peptic ulcer., Main Outcome Measures: Prevalence of hazardous prescribing events, by each event and overall, discounted quality adjusted life years (QALYs) lost, and cost to the NHS in England of managing harm., Results: QALY losses and cost increases were observed for each hazardous prescribing event ( v no hazardous prescribing event). Mean QALYs per person were between 0.01 (95% credibility interval (CI) 0.01 to 0.02) lower with history of peptic ulcer, to 0.11 (0.04 to 0.19) lower with chronic kidney disease. Mean cost increases ranged from a non-statistically significant £14 (€17; $18) (95% CI -£71 to £98) in heart failure, to a statistically significant £1097 (£236 to £2542) in people concurrently taking anticoagulants. Prevalence of hazardous prescribing events per 1000 patients ranged from 0.11 in people who have had a peptic ulcer to 1.70 in older adults. Nationally, the most common hazardous prescribing event (older adults with no gastroprotection) resulted in 1929 (1416 to 2452) QALYs lost, costing £2.46m (£0.65m to £4.68m). The greatest impact was in people concurrently taking oral anticoagulants: 2143 (894 to 4073) QALYs lost, costing £25.41m (£5.25m to £60.01m). Over 10 years, total QALYs lost were estimated to be 6335 (4471 to 8658) and an NHS cost for England of £31.43m (£9.28m to £67.11m)., Conclusions: NSAIDs continue to be a source of avoidable harm and healthcare cost in these five high risk populations, especially in inducing an acute event in people with chronic condition and people taking oral anticoagulants., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: Funding from the NIHR; DMA reports research grants from NIHR, AbbVie, Almirall, Celgene, Eli Lilly, Janssen, Novartis, UCB, and the Leo Foundation. AC, EC, BG, DM, LP, and GR report research grants from NIHR. AC reports research grants from NIHR, UKRI, and Industrial Challenge Fund. AJA reports research grants from NIHR and was National Clinical Director for NHS England at the time of the study. RAE reports research grants from NIHR and Abbott., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

The health sector is one of the components of development, social welfare and economic growth. The purpose of this study was to develop an economic evaluation model of the environmental and health costs of occupational diseases by hybrid approach. To achieve the study goal, a taxonomy of economic evaluation model of the environmental and health costs of occupational diseases has been developed. The Delphi method was used to identify health and environmental criteria and the analytic network process (ANP) method was used to weigh the sub-criteria. Finally, health and environmental cost were estimated based on the available information. Naft Subspecialty Hospital in Tehran, Iran (NSHT), was selected as the place of case study. In this study, eight and eleven sub-criteria were identified in the health and environmental sector, respectively. The ANP results indicated that the medicine and medical equipment cost criteria with a weight of 0.312 in the Medical sector, and the special and infectious waste cost criteria with a weight of 0.085 in the environmental sector were the most significant cost criteria in NSHT. Furthermore, the parametric model findings indicated that 99.84 and 0.16% of the total costs are associated with health and environmental costs, respectively. The findings indicated that 61.3% of the costs of the health sector were associated with the two sectors of medicine and medical equipment and the cost-of-service personnel, and 91.7% of the costs of the environmental sector are associated with wastewater treatment and the cost of electricity consumption. This study tried to present a quantitative model of the health and environmental costs of NSHT. Implemention of this integrated model can be a practical and effective step in allocating resources and prioritize interventions., (© 2024. The Author(s).)

This study uses the extended C-D production function method to measure the total distortion of factor prices and the distortion of capital, labor and land factor prices in China's provinces and cities. The results indicate that between 2000 and 2019, due to factors such as the dual economic structure between urban and rural areas, human intervention in the capital market, and lagging land marketization reform, both capital and land factor prices showed negative distortions, except for positive distortions in labor factor prices. The degree of this positive distortion began to gradually weaken, and even showed a negative distortion trend in some regions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lan, Li. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Using a two-step approach GMM, this study examines the short- and long-term effects of fiscal deficit on the economic growth of 42 Sub-Saharan African nations between 2011 and 2021. The World Development Index, the most reliable source, is where the panel data is taken from. Using the Levin-Lin-Chu and Hadri LM tests for unit root, it was determined that there is no risk of a random walk in the data. The study's findings indicate that while the fiscal deficit has short-term, positive, and significant benefits on the economic growth of SSA countries, it has long-term, negative repercussions. According to the system GMM's results, an increase in the fiscal deficit of SSA countries is linked to a short-term increase in economic growth of 0.036 percent, while an increase in the fiscal deficit of one percentage point is linked to a long-term decline in economic growth of SSA countries of 0.013 percent, holding all other factors constant. The study's findings also showed that the budget deficit has a larger positive short-run coefficient than a negative long-run coefficient. The study also revealed that while real effective exchange rates and inflation short-term hinder economic growth, gross fixed capital creation and real interest rates are the primary drivers of economic expansion. Long-term economic growth in the SSA countries is also found to be positively and significantly impacted by gross fixed capital formation. According to the study, SSA nations should manage their fiscal deficits and, in the long run, provide more funds for gross fixed capital development., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sore et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The objective of this study was to quantify the economic utility in Romosinuano production systems by developing a bioeconomic model assumed cow-calf, cow-calf plus stocker (CCPS), and complete cycle operations. Each system produced males for sale and females for replacement. Input parameters were established from breed data collected by AGROSAVIA. Revenues were estimated using the official cattle price, and production costs were quantified per activity. In the results, for cow-calf operations, the maximum economic utility was 244.12 USD. CCPS, yielded 231.86 USD, and Complete cycle, 268.94 USD. The genetic progress per generation for W240, W480, W24 and CI was + 3.8 kg, + 5 kg, + 5.9 kg, and -1 d, respectively. The price of livestock was the sensitized variable with the greatest impact on maximum economic utility (± 118.64 USD to ± 155.44 USD), followed by mineral supplementation (16.31 USD to ± 37.34 USD). The sensitized variables with the lowest impact were food (± 1.62 USD to ± 1.8 USD) and health plan supplies (± 6.03 USD to ± 9.13 USD). It is concluded that economic utility defined as a composite trait influenced by the characteristics that shape it favors genetic progress and the identification of animals with optimal performance in different bovine production systems., (© 2024. The Author(s).)

Background: Covid-19 has reinforced health and economic cases for investing in pandemic preparedness and response (PPR). The World Bank and World Health Organization (WHO) propose that low- and middle-income governments and donor countries should invest $31.1 billion each year for PPR. We analyse, based on the projected economic growth of countries between 2022 and 2027, how likely it is that low- and middle-income country governments and donors can mobilize the estimated funding., Methods: We modelled trends in economic growth to project domestic health spending by low- and middle-income governments and official development assistance (ODA) by donors for years 2022 to 2027. We modelled two scenarios for countries and donors - a constant and an optimistic scenario. Under the constant scenario we assume that countries and donors continue to dedicate the same proportion of their health spending and ODA as a share of gross domestic product (GDP) and gross national income (GNI), respectively, as they did during baseline (the latest year for which data are available). In the optimistic scenario, we assume a yearly increase of 2.5% in health spending as a share of GDP for countries and ODA as a share of GNI for donors., Findings: Our analysis shows that low-income countries would need to invest on average 37%, lower-middle income countries 9%, and upper-middle income countries 1%, of their total health spending on PPR each year under the constant scenario to meet the World Bank WHO targets. Donors would need to allocate on average 8% of their total ODA across all sectors to PPR each year to meet their target., Conclusions: The World Bank WHO targets for PPR will not be met unless low- and middle-income governments and donors spend a much higher share of their funding on PPR. Even under optimistic growth scenarios, low-income and lower-middle income countries will require increased support from global health donors. The donor target cannot be met using the yearly increase in ODA under any scenario. If the country and donor targets are not met, the highest-impact health security measures need to be prioritized for funding. Alternative sources of PPR financing could include global taxation (e.g., on financial transactions, carbon, or airline flights), cancelling debt, and addressing illicit financial flows. There is also a need for continued work on estimating current PPR costs and funding requirements in order to arrive at more enduring and reliable estimates., (© 2024. The Author(s).)

Background: The consumption of sugar-sweetened beverages (SSBs) is associated with obesity, metabolic diseases, and incremental healthcare costs. Given their health consequences, the World Health Organization (WHO) recommended that countries implement taxes on SSB. Over the last 10 years, obesity prevalence has almost doubled in Brazil, yet, in 2016, the Brazilian government cut the existing federal SSB taxes to their current 4%. Since 2022, a bill to impose a 20% tax on SSB has been under discussion in the Brazilian Senate. To simulate the potential impact of increasing taxes on SSB in Brazil, we aimed to estimate the price-elasticity of SSB and the potential impact of a new 20% or 30% excise SSB tax on consumption, obesity prevalence, and cost savings., Methods and Findings: Using household purchases data from the Brazilian Household Budget Survey (POF) from 2017/2018, we estimated constant elasticity regressions. We used a log-log specification by income level for all beverage categories: (1) sugar-sweetened beverages; (2) alcoholic beverages; (3) unsweetened beverages; and (4) low-calorie or artificially sweetened beverages. We estimated the adult nationwide baseline intake for each beverage category using 24-h dietary recall data collected in 2017/2018. Taking group one as the taxed beverages, we applied the price and cross-price elasticities to the baseline intake data, we obtained changes in caloric intake. The caloric reduction was introduced into an individual dynamic model to estimate changes in weight and obesity prevalence. No benefits on cost savings were modeled during the first 3 years of intervention to account for the time lag in obesity cases to reduce costs. We multiplied the reduction in obesity cases during 7 years by the obesity costs per capita to predict the costs savings attributable to the sweetened beverage tax. SSB price elasticities were higher among the lowest tertile of income (-1.24) than in the highest income tertile (-1.13), and cross-price elasticities suggest SSB were weakly substituted by milk, water, and 100% fruit juices. We estimated a caloric change of -17.3 kcal/day/person under a 20% excise tax and -25.9 kcal/day/person under a 30% tax. Ten years after implementation, a 20% tax is expected to reduce obesity prevalence by 6.7%; 9.1% for a 30% tax. These reductions translate into a -2.8 million and -3.8 million obesity cases for a 20% and 30% tax, respectively, and a reduction of $US 13.3 billion and $US 17.9 billion in obesity costs over 10 years for a 20% and 30% tax, respectively. Study limitations include using a quantile distribution method to adjust self-reported baseline weight and height, which could be insufficient to correct for reporting bias; also, weight, height, and physical activity were assumed to be steady over time., Conclusions: Adding a 20% to 30% excise tax on top of Brazil's current federal tax could help to reduce the consumption of ultra-processed beverages, empty calories, and body weight while avoiding large health-related costs. Given the recent cuts to SSB taxes in Brazil, a program to revise and implement excise taxes could prove beneficial for the Brazilian population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Basto-Abreu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Modern urban dynamics are increasingly shaped by the interplay between economic policy and urban planning, yet often lack an integrated approach. This study bridges this gap by examining the dynamic equilibrium between these two realms using the "Oscillation and Wave Framework." Specifically, we focus on the impact of variations in congestion parameter λ on urban sectoral spatial distribution and population dynamics. Our approach utilizes an advanced agent-based model to simulate interactions within an urban economic landscape, offering a detailed analysis of the relationship between agglomeration economies and congestion diseconomies. The results highlight the significant influence of congestion parameter adjustments on urban patterns, particularly in terms of cluster density and development. Therefore, this study not only provides a deeper understanding of the intricate balance between economic and urban planning factors but also emphasizes the necessity of incorporating these insights into urban planning and policy formulation for sustainable urban development. The findings also have important practical implications for addressing the dynamic complexities of urban environments, especially the interactions between different industries and their role in shaping urban structures., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Three randomised controlled trials (RCTs) have demonstrated that first-line cryoballoon pulmonary vein isolation decreases atrial tachycardia in patients with symptomatic paroxysmal atrial fibrillation (PAF) compared with antiarrhythmic drugs (AADs). The aim of this study was to develop a cost-effectiveness model (CEM) for first-line cryoablation compared with first-line AADs for the treatment of PAF. The model used a Danish healthcare perspective., Methods: Individual patient-level data from the Cryo-FIRST, STOP AF and EARLY-AF RCTs were used to parameterise the CEM. The model structure consisted of a hybrid decision tree (one-year time horizon) and a Markov model (40-year time horizon, with a three-month cycle length). Health-related quality of life was expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3% per year. Model outcomes were produced using probabilistic sensitivity analysis., Results: First-line cryoablation is dominant, meaning it results in lower costs (-€2,663) and more QALYs (0.18) when compared to first-line AADs. First-line cryoablation also has a 99.96% probability of being cost-effective, at a cost-effectiveness threshold of €23,200 per QALY gained. Regardless of initial treatment, patients were expected to receive ∼ 1.2 ablation procedures over a lifetime horizon., Conclusion: First-line cryoablation is both more effective and less costly (i.e. dominant), when compared with AADs for patients with symptomatic PAF in a Danish healthcare system., (© 2024. The Author(s).)

Sound ecological and environmental governance systems are critical for promoting green and low-carbon economic transformation and high-quality development. However, financing constraints are major obstacle to the revitalization and transformation of China's real economy. In this study, we constructed an environmental dynamic stochastic general equilibrium (E-DSGE) model that incorporates two types of environmental expenditure and financing constraints, and discussed their economic and environmental effects. Based on this, we further considered the impacts of financing constraints on policy effects. Firstly, we found that increases in carbon emission reduction subsidies in government expenditure (1) increase total economic output and (2) motivate enterprises to increase emission reduction efforts and reduce pollution intensity and emissions, thereby reducing the inventory of environmental pollutants while balancing economic benefits and emission reduction. Secondly, increasing the proportion of government special expenditure on environmental protection promote output growth and directly reduces the pollution stock in the environment. However, such policies may also reduce the emission reduction efforts of enterprises, leading to increases in their pollution emissions and intensity. Lastly, the existence of financing constraints is not conducive to the growth of total output but increases the pollution control effect of emission reduction subsidies and pollution prevention expenditure. Application of the E-DSGE model offers new theoretical insight into environmental economics and macroeconomics. Moreover, the results of this study provide a reference for optimizing the structure of fiscal expenditure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The vegetable sector is a vital pillar of society and an indispensable part of the national economic structure. As a significant segment of the agricultural market, accurately forecasting vegetable prices holds significant importance. Vegetable market pricing is subject to a myriad of complex influences, resulting in nonlinear patterns that conventional time series methodologies often struggle to decode. In this paper, we exploit the average daily price data of six distinct types of vegetables sourced from seven key wholesale markets in Beijing, spanning from 2009 to 2023. Upon training an LSTM model, we discovered that it exhibited exceptional performance on the test dataset. Demonstrating robust predictive performance across various vegetable categories, the LSTM model shows commendable generalization abilities. Moreover, LSTM model has a higher accuracy compared to several machine learning methods, including CNN-based time series forecasting approaches. With R2 score of 0.958 and MAE of 0.143, our LSTM model registers an enhancement of over 5% in forecast accuracy relative to conventional machine learning counterparts. Therefore, by predicting vegetable prices for the upcoming week, we envision this LSTM model application in real-world settings to aid growers, consumers, and policymakers in facilitating informed decision-making. The insights derived from this forecasting research could augment market transparency and optimize supply chain management. Furthermore, it contributes to the market stability and the balance of supply and demand, offering a valuable reference for the sustainable development of the vegetable industry., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Under economic globalization, countries are linked through trade and investments. This economic interdependence creates vulnerabilities. The indirect vulnerability induced by interdependent networks of trade and investments can put a country's economy at risk, but this risk has yet to be systematically quantified and investigated. In this paper, we developed the novel Potential Indirect Vulnerability Index (PIVI) to capture how interdependencies between networks of trade and foreign direct investment (FDI) may induce economic vulnerabilities. The model consisted of three main components: a target country (the importer of goods), an investing country (the exporter of FDI), and the intermediary countries that export commodities to the target country and receive FDI from the investing country, serving as conduits of the vulnerabilities caused indirectly by the investing country. The PIVI quantifies the indirect vulnerabilities based on the product of two fractions: 1) the dependency of the target country on commodities from each intermediary country; and 2) the dependency of each intermediary country on FDI from the investing country. We demonstrated the utility of PIVI by examining the US economy's vulnerability to China using 2019 trade and FDI data. Several Asian countries and a mix of agricultural products and raw materials were identified as conduits through which China could potentially influence the US economy. Vietnam was a sizeable risk because, while it has been a primary source of many US imports, it also received about 30% of its FDI from China. The US policy makers might opt to increase diversity in trade partners or to promote investment in countries such as Vietnam. We also applied the PIVI analysis to critical minerals, identifying cobalt, tungsten, and copper as the most vulnerability-inducing among them. PIVI is a flexible metric than can be aggregated and modified to provide a more nuanced and focused assessment of an economy's vulnerability., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pourshahabi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The complex financial networks, with their nonlinear nature, often exhibit considerable noises, inhibiting the analysis of the market dynamics and portfolio optimization. Existing studies mainly focus on the application of the global motion filtering on the linear matrix to reduce the noise interference. To minimize the noise in complex financial networks and enhance timing strategies, we introduce an advanced methodology employing global motion filtering on nonlinear dynamic networks derived from mutual information. Subsequently, we construct investment portfolios, focusing on peripheral stocks in both the Chinese and American markets. We utilize the growth and decline patterns of the eigenvalue associated with the global motion to identify trends in collective market movement, revealing the distinctive portfolio performance during periods of reinforced and weakened collective movements and further enhancing the strategy performance. Notably, this is the first instance of applying global motion filtering to mutual information networks to construct an investment portfolio focused on peripheral stocks. The comparative analysis demonstrates that portfolios comprising peripheral stocks within global-motion-filtered mutual information networks exhibit higher Sharpe and Sortino ratios compared to those derived from global-motion-filtered Pearson correlation networks, as well as from full mutual information and Pearson correlation matrices. Moreover, the performance of our strategies proves robust across bearish markets, bullish markets, and turbulent market conditions. Beyond enhancing the portfolio optimization, our results provide significant potential implications for diverse research fields such as biological, atmospheric, and neural sciences., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Peng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Against the background of digital development, this study's research object is the platform-based highway transportation supply chain. It also analyzes two modes of supply chain financial credit financing, namely, upstream, and downstream enterprises of the platform, and network freight platform as the main financing body. Notably, the financial provider sets up a transaction credit based on the principle of business truth, and closed-loop transactions, determine the upper limit of the credit line based on the principle of financing self-compensation, build the expected profit maximization model, and establish the optimal credit line. Combined with the Highway Freight Index and Logistics Prosperity Index, the dynamic early warning value is established for the financing mode, where the platform as the main financing body. Through numerical analysis, the credit line and expected profit increase with the transaction credit, expected freight volume, and credit interest rate under the two modes, and the increase deriving from the credit interest rate is more significant. Finally, this paper describes the two-dimensional credit matrix of the financing subject via transaction credit and credit interest rate, which provides an intuitive credit reference for financial institutions to conduct the credit financing of the platform-based highway transportation supply chain., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Shared manufacturing is a new business form that focuses on all aspects of production and manufacturing, mainly relying on the shared manufacturing platform to achieve the optimal allocation of idle resources. For enterprises, in the process of deciding to lease idle resources, the pricing and advertising investment efficiency of the shared manufacturing platform is a valuable research issue. The shared manufacturing model in this paper consists of one manufacturer and one shared manufacturing platform, which will invest in cooperative advertising while the shared manufacturing process is completed. The cooperative advertising involves four models: the traditional cooperation model, the cost-sharing contract model, the revenue-sharing contract model, and the bilateral cost-sharing contract model. We investigate the impact of some key parameters on the prices and profits of the manufacturer and the shared manufacturing platform based on the differential game. The numerical examples demonstrate the viability of the model. Finally, we provide suggestions based on the decision-making of the manufacturer and the shared manufacturing platform under different cooperative advertising models., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wu, Liu. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This research explores the link between stock markets and banking deposits in South Asian (Pakistan, India, Sri Lanka, Nepal) countries. This study empirically examines the systemic risk potential of financial institutions in South Asia using current systemic risk statistics. Yearly data on stock prices and banking deposits from January 2000 to December 2020 were analyzed using a two-stage process. In the first phase, we measure VaR (value at risk), and in the second step, we measure the DCC GARCH model for our empirical analysis. The study findings reveal systemic risk spillover between the stock markets of South Asian countries and the relevant country's banking system deposits. The policymakers can use our study findings to create a more sustainable financial sector., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: In Italy, post-liver transplant (LT) hepatitis B virus (HBV) reinfection prophylaxis is frequently based on a combined regimen of anti-HBV immunoglobulin (HBIG) and oral antivirals. However, little information is available at the national level on the cost of LT and the contribution of HBV prophylaxis. This study aimed to quantify the direct healthcare cost for adult patients undergoing LT for HBV-related disease over a lifetime horizon and from the perspective of a National Healthcare Service., Methods: A pharmaco-economic model was implemented with a 4-tiered approach consisting of 1) preliminary literature research to define the research question; 2) pragmatic literature review to retrieve existing information and inform the model; 3) micro-simulated patient cycles; and 4) validation from a panel of national experts., Results: The average lifetime healthcare cost of LT for HBV-related disease was €395,986. The greatest cost drivers were post-transplant end-stage renal failure (31.9% of the total), immunosuppression (20.6%), and acute transplant phase (15.8%). HBV reinfection prophylaxis with HBIG and antivirals accounted for 12.4% and 6.4% of the total cost, respectively; however, lifetime HBIG prophylaxis was only associated with a 6.6% increase (~€422 k). Various sensitivity analyses have shown that discount rates have the greatest impact on total costs., Conclusion: This analysis showed that the burden of LT due to HBV is not only clinical but also economic., Competing Interests: BC, FF, and CV were employees of IQVIA Solutions S.r.l., which received a grant from Kedrion Biopharma Inc. to conduct the study. LC, PS, SF, AM, and MR received a fee from IQVIA Solutions S.r.l. as Advisors., (Copyright © 2024 Marzano, Canali, De Carlis, De Simone, Fiorentino, Rendina, Vassallo and Fagiuoli.)