Markov Model Research Articles

Therapies for Advanced Parkinson's Disease in Sweden: A Cost-Effectiveness Analysis Using Real-World Data.

The Swedish Parkinson's Disease (PD) Registry provides rich data on cost and quality of life for patients receiving device-aided therapies (DATs) for Parkinson's disease in Sweden. This study sought to use this real-world evidence to determine the cost-effectiveness profile of specific DATs in Sweden. We developed a state transition (Markov) model to represent disease progression over time and used published clinical data to represent short- and long-term disease outcomes. We used data from the Swedish PD Registry to assign costs and quality of life measures (utilities) to each health state and modelled total costs and outcomes over a 20-year time horizon. The four treatment groups modelled were: best medical therapy, deep brain stimulation, levodopa-carbidopa intestinal gel, and continuous subcutaneous apomorphine infusion. We calculated results from both payer and societal perspectives. The most cost-effective intervention was deep brain stimulation (DBS), which dominated all other interventions. Sensitivity analysis indicated that the key drivers of uncertainty were the transition probabilities between successive Hoehn and Yahr stages on each treatment. Results were consistent from both payer and societal perspectives. DBS is a cost-effective use of resources in Sweden. However, uncertainty remains regarding long-term symptom control as well as quality of life within specific health states for all device-aided therapies, and further data are needed to fully validate the model projections and provide more insight into areas of future research.

Cost-Effectiveness of Implantable Cardioverter-Defibrillators in Surgically Repaired Tetralogy of Fallot.

Implantable cardioverter-defibrillators (ICDs) are increasingly used in patients with congenital heart disease, most commonly in surgically repaired Tetralogy of Fallot (rTOF). Studies have examined patient outcomes after ICD implantation; however, the cost-effectiveness of ICDs in rTOF is unknown. We sought to evaluate the cost-effectiveness of typical medical management plus ICD (TMM + ICD) for primary prevention of sudden cardiac death (SCD) compared to typical management alone (TMM) in high-risk patients with rTOF. We created a Markov model to compare costs and quality of life (QOL) of TMM + ICD vs TMM for a hypothetical adolescent with rTOF and higher than average risk of SCD over 20years. Model parameters were derived from the literature and institutional data. We assumed that SCD risk increased from 0.4%/year to 1.2%/year over 20years, that the ICD was 99% effective in preventing SCD, and a frequency of ICD replacement of 11years. We used sensitivity analyses to explore uncertainty around model assumptions. Costs were $62,895 for TMM + ICD and $19,004 for TMM. The incremental cost-effectiveness ratio for TMM + ICD was $53,386/quality-adjusted life-year (QALY) which is below threshold of $100,000/QALY that is usually considered cost-effective. The model was sensitive to SCD risk, costs of ICD implantation and management, cost of ICD replacement, and utilities of living with rTOF and of ICD implantation. Based on risk of SCD, cost of device implantation and management including complications, and our current understanding of the impact of ICD implantation on patient QOL, ICD therapy for primary prevention of SCD in rTOF can constitute a cost-effective strategy.

Cost-effectiveness analysis of subcutaneous biosimilar tocilizumab in patients with rheumatoid arthritis in Spain.

Cost-effectiveness analysis of subcutaneous biosimilar tocilizumab in patients with rheumatoid arthritis in Spain.

Cost-Effectiveness of Aortic Valve Replacement in Low- and Intermediate-Risk Chinese Patients With Severe Aortic Stenosis.

Transcatheter aortic valve replacement (TAVR) remains debated as an alternative to surgical aortic valve replacement (SAVR). We aimed to evaluate the cost-effectiveness of aortic valve replacement strategies in low- and intermediate-risk patients with severe aortic stenosis in China. A decision-analytic model combining decision tree and Markov model was developed to compare outcomes of universal SAVR, universal TAVR, and a risk-based strategy (SAVR in low-risk patients and TAVR in intermediate-risk patients) in a hypothetical cohort of 75-year-old patients with aortic stenosis within the perspective of the Chinese health care system. A meta-analysis was performed to derive the clinical inputs; the 2019 to 2021 claims data from Shaanxi Province were used for cost analysis, and quality of life was measured using EuroQoL-5D. One-way and probabilistic (10 000 Monte Carlo simulations) sensitivity analyses were conducted to examine the robustness of model results. Primary outcomes included total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Universal TAVR gained the most QALYs (6.76 QALYs) with the highest costs (USD 58 949). Compared with universal SAVR, the risk-based strategy gained 0.12 additional QALYs at higher costs (USD 14 046); the ICER (117 048 USD/QALY) exceeded the willingness-to-pay threshold (37 657 USD/QALY, 3-fold gross domestic product per capita in China). The ICER of universal TAVR versus universal SAVR (80 526 USD/QALY) also exceeded the willingness-to-pay threshold. Sensitivity analysis showed that universal TAVR would be cost-effective if TAVR valve costs were <USD 21 477 (>44.23% cost reduction). Subgroup analysis showed that universal TAVR and risk-based strategy remained not cost-effective compared with universal SAVR in both low-risk (ICER of 64 414 USD/QALY) and intermediate-risk (ICER of 124 851 USD/QALY) patients. In 10 000 Monte Carlo simulations, the probabilities of being cost-effective for universal SAVR, universal TAVR, and risk-based strategy were 89.81%, 10.14%, and 0.05%, respectively. The risk-based strategy and universal TAVR appeared not to be cost-effective versus universal SAVR in low- and intermediate-risk patients with severe aortic stenosis in China.

Impacts of tourism on LULC and LST dynamics in district Buner and Shangla, Pakistan

Tourism activities are changing the global landscape pattern. This study attempted to estimate changes in Land Use Land Cover (LULC) and Land Surface Temperature (LST) in District Buner and Shangla, Khyber Pakhtunkhwa (KPK), Pakistan, and specifically its tourist spots. Using remote sensing data from satellites (1990–2020) and future projections (2035–2050), we applied Artificial Neural Network (ANN) and Cellular Automata Markov (CA-Markov) models to examine past and future LULC and LST dynamics across two districts including four major tourist spots (Shangla Top as tourist spot one (TS1), Bar Puran (TS2), Shahida Sar (TS3), and Daggar (TS4). The LULC classification for the whole study area (1990–2020) indicates that built-up and agricultural areas increased with a net change of +0.8% and +3.2% for the Shangla and Buner districts, respectively. The highest mean LST was found in the built-up areas. The simulation results indicate an expansion of 4.5% and 5.8% of the total built-up areas, and the LST above 31 °C will cover 76% and 88% of the total areas in 2035 and 2050, respectively. This conversion is driven by tourism activities, causing urban heat island effects (UHIs), and environmental degradation. The analysis of tourist spots (1990–2020) shows the highest change in built-up areas at Shangla Top (TS1), while the highest LST (28 °C) for the Daggar (TS4). The future simulation (2035–2050) results for tourist spots show that TS4 would have the highest LULC change in built-up areas (5.67%), and TS4 would have the highest LST (31 °C) from 65.23 to 82.20%. These findings provide an essential understandings for developing long-term tourism policies meant to moderate the environmental impact of tourism in the region.

A structured coalescent model reveals deep ancestral structure shared by all modern humans.

Understanding the history of admixture events and population size changes leading to modern humans is central to human evolutionary genetics. Here we introduce a coalescence-based hidden Markov model, cobraa, that explicitly represents an ancestral population split and rejoin, and demonstrate its application on simulated and real data across multiple species. Using cobraa, we present evidence for an extended period of structure in the history of all modern humans, in which two ancestral populations that diverged ~1.5 million years ago came together in an admixture event ~300 thousand years ago, in a ratio of ~80:20%. Immediately after their divergence, we detect a strong bottleneck in the major ancestral population. We inferred regions of the present-day genome derived from each ancestral population, finding that material from the minority correlates strongly with distance to coding sequence, suggesting it was deleterious against the majority background. Moreover, we found a strong correlation between regions of majority ancestry and human-Neanderthal or human-Denisovan divergence, suggesting the majority population was also ancestral to those archaic humans.

Modelling occult lymph node metastases in HNSCC patients with a trinary state hidden Markov model.

Head-and-neck squamous cell carcinoma frequently metastasize through lymphatic&#xD;system. Occult metastases are challenging for designing radiotherapy treatment volumes. Literature&#xD;values indicate that around 20% of lymph node metastases are clinically undetected. However, recent&#xD;data suggest that this value is only representative for level II whereas the rate of occult metastases&#xD;is substantially higher in levels III and IV. , while occult metastases are more common in levels III&#xD;and IV.&#xD;Approach: We propose a trinary-state Hidden Markov Model to describe ipsilateral lymphatic&#xD;tumor progression over time. Each lymph node level (LNL) can be in one of three states: healthy,&#xD;microscopically (pathologically) involved, or macroscopically (clinically) involved. In each time step,&#xD;a healthy LNL may become microscopically involved due to spread from the primary tumor or an&#xD;involved upstream LNL. In addition, a microscopically involved LNL may transition to macroscop-&#xD;ically involved. The probability of occult metastases is obtained as the conditional probability of&#xD;being in the microscopically involved state given the individual patient's macroscopic involvement.&#xD;Model parameters are learned from a dataset of 550 patients, including 263 with both pathological&#xD;and clinical LNL involvement reported.&#xD;Main Results: For oropharyngeal SCC, the model estimates an occult metastases probability&#xD;below 5% in LNL IV unless LNL III is clinically positive, suggesting potential for reducing elective&#xD;clinical target volumes. The model's estimated rate of clinically undetected metastases is 82%, 41%,&#xD;and 34% for LNL II, III, and IV, respectively, which agrees with the data.&#xD;Significance: The proposed trinary-state HMM represents a methodological extension to a previ-&#xD;ously published binary-state HMM. The binary HMM distinguished the microscopic and macroscopic&#xD;involvement via the concept of sensitivity, which may underestimate the risk of occult metastases. The&#xD;trinary HMM addresses this problem and represents a more natural description of tumor progression.

Like mother, like daughter? Phenotypic plasticity, environmental covariation, and heritability of size in a parthenogenetic wasp.

Parthenogenetic wasps provide an ideal natural experiment to study the heritability, plasticity, and microevolutionary dynamics of body size. Dinocampus coccinellae (Hymenoptera:Braconidae, Euphorinae) is a solitary, generalist braconid parasitoid wasp that reproduces through thelytokous parthenogenesis, and parasitizes over fifty diverse species of coccinellid ladybeetles worldwide as hosts. Here we designed an experiment with parthenogenetic lines of D. coccinellae presented with three different host ladybeetle species of varying sizes, across multiple generations to investigate heritability, and plasticity of body size measured via a combination of morphometric variables such as thorax width, abdominal width, and wing length in D. coccinellae. We expected positively correlated parent-offspring parasitoid regressions, indicative of heritable size variation, from unilineal (parent and offspring reared on same host species) lines, since these restrict environmental variation in phenotypes. In contrast, because multilineal (parent and offspring reared on different host species) lines would induce phenotypic plasticity of clones reared in varying environments, we expected negatively correlated parent-offspring parasitoid regressions. Our results indicate (1) little heritable variation in body size, (2) strong independence of offspring size on the host environment, (3) small mothers produce larger offspring, and vice versa, independent of host. We then model the evolution of size and host-shifting under a constrained fecundity advantage model of Cope's Law using a Hidden Markov Model, showing that D. coccinellae likely has fitness advantages to maintain plasticity in body size despite parthenogenetic reproduction.

Statins for primary prevention of cardiovascular disease in Germany: benefits and costs.

The reduction of LDL cholesterol lowers the risk of coronary and cerebrovascular events in individuals without manifest cardiovascular diseases. In Germany, statins at the expense of statutory health insurance had only been permitted for patients with atherosclerosis-related diseases or those at high cardiovascular risk (over 20 percent event probability within the next 10years, calculated using one of the "available risk calculators"). However, international guidelines recommend lower risk thresholds for the use of statins. The health and economic impacts of different risk thresholds for statin use in primary prevention within the German population are estimated for thresholds of 7.5, 10, and 15 percent over 10years, based on the US Pooled Cohort Equation (PCE) which is valid for Germany, using Markov models. Cost-effectiveness increases with a rising risk threshold, while individual benefit decreases with age at the start of treatment. The use of statins at a risk of 7.5 percent or more is cost-effective at any age (cost per QALY between 410 and 2100 Euros). In none of the examined scenarios does the proportion of the population qualifying for statin therapy exceed 25 percent. Lowering the threshold for statin therapy to a risk of 7.5 percent of either non-fatal myocardial infarction, coronary heart disease death, non-fatal or fatal stroke would align statin prescription in Germany with international standards. There is no urgent rationale for applying age-stratified risk thresholds.

Asynchronous output feedback control for singular Markovian jump systems under input saturation

This paper analyzes the problem of asynchronous control for singular Markovian jump systems (SMJSs) under input saturation via dynamic output feedback (DOF) control technology. The DOF controller modes do not need to be synchronized with the system modes and a hidden Markov model (HMM) is adopted to characterize this phenomenon. A convex set method is used to solve the saturation problem. Firstly, a sufficient condition is derived to guarantee that the system is stochastically admissible (SA) with H ∞ performance. Secondly, the solution to solving DOF controller gains is obtained. Moreover, the maximization domain of attraction (DOA) is estimated by optimal algorithm. Finally, two examples are given to show the effectiveness of the proposed method.

Space-Time Estimation of Built-Up Landscape of Ilorin Metropolis, Nigeria

This paper assesses the spatiotemporal dynamics of the built-up environment in Ilorin, Nigeria, and appraises the landscape changes between 1986 and 2020. The study used information from the United States Geological Survey (USGS) with remote sensing and Geographic Information Systems (GIS) as major analyses instruments. Employing the Markov model and artificial neural networks (ANN), particularly multilayer perceptron (MLP) models, the study predicts future land loss surrendered to urbanization processes. The study employed Landsat 4–5, 7, and 8 images of Ilorin administrative areas for five epochs: 1986, 1996, 2006, 2016, and 2020 for land cover monitoring. The Environment for Visualizing Images (ENVI) and ArcGIS software were utilized for image classification, enhancement, processing, analysis, and land use map production. Calculations of land consumption rate (LCR) and land absorption coefficient (LAC) revealed increased land consumption from 3757.23 ha in 1986 to 15,925.17 ha in 2020, with a fluctuating LAC influenced by historical events and specific government policies measured by different regimes. The land development index (LDI) indicated urban expansion trends, emphasizing the need for a comprehensive approach encompassing environmental, social, economic, and institutional dimensions for sustainable development in Ilorin.

Cost-effectiveness analysis of combination therapies involving novel agents for first/second-relapse patients with multiple myeloma: a Markov model approach with calibration techniques

BackgroundAs the number of randomized clinical trials (RCTs) demonstrating the survival benefits of combination therapies in previously treated multiple myeloma (MM) patients increases, it is essential to determine the most cost-effective treatment through robust economic evaluation. This study aims to assess the cost-effectiveness of combination therapies for first/second-relapse MM patients from the perspective of the Chinese healthcare system.MethodsA Markov model was developed to evaluate three combination therapy groups based on primary drugs (bortezomib, lenalidomide, and carfilzomib). The economic evaluation was conducted within each group individually, rather than across different groups. Clinical inputs for the model were derived from RCT reports, while healthcare costs were sourced from the Zhejiang Province bidding database and a retrospective analysis. Utility values were obtained through an on-site survey using the Chinese version of the EuroQoL Five-dimensional Five-level Questionnaire. One-way and probabilistic sensitivity analyses were performed to assess the robustness of the base-case results.ResultsIn the bortezomib group, bortezomib-dexamethasone (Vd) yielded 2.42 quality-adjusted life years (QALYs) at a cost of ¥783,775. With a willingness-to-pay (WTP) threshold of three times the 2023 per capita GDP in China (¥258,074), pomalidomide-bortezomib-dexamethasone was the most cost-effective therapy (¥86,129/QALY) in this group. In the lenalidomide group, lenalidomide-dexamethasone (Rd) resulted in 3.06 QALYs at a cost of ¥840,509. Compared to Rd, the incremental cost-effectiveness ratios (ICERs) of elotuzumab-lenalidomide-dexamethasone (¥5,095,300/QALY), ixazomib-lenalidomide-dexamethasone (¥1,605,712/QALY), carfilzomib-lenalidomide-dexamethasone (¥955,255/QALY), and daratumumab-lenalidomide-dexamethasone (¥851,933/QALY) all exceeded the WTP threshold. In the carfilzomib group, carfilzomib-dexamethasone (Kd) resulted in 3.19 QALYs at a cost of ¥1,961,624. Compared to Kd, the ICERs of daratumumab-carfilzomib-dexamethasone (¥2,250,821/QALY) and isatuximab-carfilzomib-dexamethasone (¥4,977,964/QALY) also exceeded the WTP. Sensitivity analyses confirmed the robustness of the base-case results.ConclusionsAlthough this study did not fully account for the heterogeneity of subsequent treatment regimens among first/second-relapse MM patients, it highlights that the substantial financial burden associated with combination therapies involving novel agents poses a significant challenge in justifying their economic value.

Unsealing behaviour: Variation in harbour seal (Phoca vitulina) responses to anthropogenic sound in relation to individual health.

Unsealing behaviour: Variation in harbour seal (Phoca vitulina) responses to anthropogenic sound in relation to individual health.

Cost-effectiveness analysis of bispecific antibody faricimab for treatment of neovascular age-related macular degeneration and diabetic macular edema in Japan

Objective To assess the cost-effectiveness of faricimab versus other anti-vascular endothelial growth factor (anti-VEGF) drugs for treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) in Japan, while considering societal burden associated with treatment. Methods A Markov model for cost-effectiveness analysis of anti-VEGF treatment in patients with nAMD and DME was applied based on cost and utility value data from Japan. Faricimab administered through a treat-and-extend (T&E) regimen was compared with ranibizumab administered pro re nata (PRN) and T&E, aflibercept T&E, brolucizumab T&E, and best supportive care (BSC). Further to treatment costs (public payer perspective), the societal burden (societal perspective), including costs of travel, informal care, and productivity, was assessed. Results In treatment of nAMD, lifetime quality-adjusted life years (QALYs) gained were highest with faricimab (faricimab T&E: 6.92, ranibizumab PRN: 6.88, ranibizumab T&E: 6.91, aflibercept T&E: 6.89, brolucizumab T&E: 6.89, BSC: 5.99). From the public payer perspective, the lifetime total cost for faricimab T&E was lower than those for ranibizumab (PRN T&E) and brolucizumab, was comparable to aflibercept T&E, and higher than BSC (incremental costs: 158,385 and 6,475,511 JPY, respectively). As a result, faricimab was cost-effective or dominant in the treatment of nAMD, excluding BSC. From the societal perspective, faricimab was dominant against all comparators in nAMD. In treatment of DME, QALYs gained were highest with faricimab (faricimab T&E: 8.51, ranibizumab PRN: 8.17, aflibercept PRN: 8.36, ranibizumab T&E: 8.13, BSC: 5.16). From both the public payer and societal perspectives, faricimab was dominant against all comparators in DME. Conclusions When societal burdens were considered, faricimab was dominant in both nAMD and DME against all comparators, suggesting that the extended dosing interval associated with faricimab treatment may alleviate societal burdens and consequently improve patient outcomes.

Health Economic Benefit Analysis of ENT Centers: Simulation-based analysis of centralization in laryngeal surgery using population data from Schleswig-Holstein, exemplified by laryngeal carcinoma

The health economic impacts of centralization in the German healthcare system, particularly in the field of ENT, are insufficiently researched. Therefore, this study investigates the potential benefits of a head and neck tumor center using the example of surgical care for laryngeal carcinoma in Schleswig-Holstein.A systematic literature review was conducted using the PRISMA search schema to examine the correlation between a hospital's treatment volume and mortality rates for laryngeal carcinomas. Subsequently, an 8-year Markov model simulation was employed to demonstrate the effects of establishing centers. This was supplemented by a cost analysis based on data from the PROGNOS study.The simulation shows the hypothetical impact on patient care for the existing head and neck tumor center in Schleswig-Holstein over an 8-year period. Maintaining the center in Schleswig-Holstein over eight years would save 113 lives and gain 1,333 life years (equivalent to 933.1 QALYs), corresponding to costs of 12,866 euros per QALY.The results suggest that centralizing care has medical and economic effectiveness in the ENT sector. They provide important insights for current political discussions and decision-making processes in healthcare. Future research should expand the focus to include other ENT cancers to gain a more comprehensive understanding of the impacts of centralization.

Factors shaping vaginal microbiota long-term community dynamics in young adult women.

The vaginal microbiota is known to affect women's health. Yet, there is a notable paucity of high-resolution follow-up studies lasting several months, which would be required to interrogate the long-term dynamics and associations with demographic and behavioural covariates. Here, we present a high-resolution longitudinal cohort study of 125 women, followed for a median duration of 8.6 months, with a median of 11 samples collected per woman. Using a hierarchical Bayesian Markov model, we characterised the patterns of vaginal microbiota community persistence and transition, simultaneously estimated the impact of 16 covariates and quantified individual variability among women. We showed that "optimal" (Community State Type (CST) I, II, and V) and "sub-optimal" (CST III) communities are more stable over time than "non-optimal" (CST IV) ones. Furthermore, we found that some covariates - most notably alcohol consumption - impacted the probability of shifting from one CST to another. We performed counterfactual simulations to confirm that alterations of key covariates, such as alcohol consumption, could shape the prevalence of different microbiota communities in the population. Finally, our analyses indicated that there is a relatively canalised pathway leading to the deterioration of vaginal microbiota communities, whereas the paths to recovery can be highly individualised among women. In addition to providing one of the first insights into vaginal microbiota dynamics over a year, our study showcases a novel application of a hierarchical Bayesian Markov model to clinical cohort data with many covariates. Our findings pave the way for an improved mechanistic understanding of microbial dynamics in the vaginal environment and the development of novel preventative and therapeutic strategies to improve vaginal health.

Characterising symptomatic substates in individuals on the psychosis continuum: a hidden Markov modelling approach.

To improve early intervention and personalise treatment for individuals early on the psychosis continuum, a greater understanding of symptom dynamics is required. We address this by identifying and evaluating the movement between empirically derived attenuated psychotic symptomatic substates-clusters of symptoms that occur within individuals over time. Data came from a 90-day daily diary study evaluating attenuated psychotic and affective symptoms. The sample included 96 individuals aged 18-35 on the psychosis continuum, divided into four subgroups of increasing severity based on their psychometric risk of psychosis, with the fourth meeting ultra-high risk (UHR) criteria. A multilevel hidden Markov modelling (HMM) approach was used to characterise and determine the probability of switching between symptomatic substates. Individual substate trajectories and time spent in each substate were subsequently assessed. Four substates of increasing psychopathological severity were identified: (1) low-grade affective symptoms with negligible psychotic symptoms; (2) low levels of nonbizarre ideas with moderate affective symptoms; (3) low levels of nonbizarre ideas and unusual thought content, with moderate affective symptoms; and (4) moderate levels of nonbizarre ideas, unusual thought content, and affective symptoms. Perceptual disturbances predominantly occurred within the third and fourth substates. UHR individuals had a reduced probability of switching out of the two most severe substates. Findings suggest that individuals reporting unusual thought content, rather than nonbizarre ideas in isolation, may exhibit symptom dynamics with greater psychopathological severity. Individuals at a higher risk of psychosis exhibited persistently severe symptom dynamics, indicating a potential reduction in psychological flexibility.

Room-level domestic occupancy simulation model using time use survey data

To minimize the energy performance gap between expected and actual energy usage in buildings, it is crucial to accurately represent occupant behaviour, which significantly impacts building performance. With improved building insulation standards, the impact of occupant actions becomes more pronounced. Most domestic occupancy models use three general states: present & awake, present & sleeping, and absent. However, in residential buildings, room-level presence information is essential for accurately evaluating energy demands, as specific activities occur in specific rooms. The novelty of this study lies in the simulation of occupancy at the room level. Using data from a Danish time-use survey, a hidden Markov model was fitted to estimate transition probabilities between five states: bedroom, kitchen, bathroom, living room, and not present, based on recorded activities. An online application of the model is available (Link: https://proccs.compute.dtu.dk), enabling researchers or building designers to create room-level occupancy profiles for use in building energy performance tools, providing a more accurate representation of household occupancy.

A Markov Model Unveiling the Impact of Resmetirom on the Natural History of MASLD Patients: A Sistematic Review and Meta-Analysis.

The MAESTRO-NASH phase 3 trial reported that a 52-week treatment of Resmetirom is effective in improving fibrosis and metabolic dysfunction-associated steatohepatitis (MASH) in patients with MASH and F2 or F3 fibrosis, while data on the impact on 5-year and long-term clinical outcomes are still lacking. We simulated the transition probabilities of disease progression in MASLD patients with F2 or F3 fibrosis and the effect of Resmetirom treatment on clinical outcomes. A meta-analysis of literature data formed transition matrices for fibrosis stages and complications, defined as compensated (CC) and decompensated cirrhosis (DC), hepatocellular carcinoma (HCC) and mortality-liver-related mortality (LR-M), cardiovascular mortality (CV-M) and extra-hepatic cancer mortality (EHC-M). Markov model was developed to depict the F2 and F3 fibrosis stage progression towards the complications and to evaluate the effect of Resmetirom treatment on the natural history of MASLD. We estimated the 5-year probability of Resmetirom-treated and untreated MASLD patients with baseline F2 fibrosis of developing CC (5.16% vs. 6.82%, respectively), DC (0.25% vs. 0.3%, respectively), HCC (0.25% vs. 0.32%, respectively) and mortality (0.15% vs. 0.16% for LR-M; 1.02% vs. 1.1% for CV-M; 1.07% vs. 1.2% for EHC-M, respectively). Similarly, we estimated the five-year probability of Resmetirom-treated and untreated MASLD patients with baseline F3 fibrosis of developing CC (17.12% vs. 21.34%, respectively), DC(1.1% vs. 1.47%, respectively), HCC (1.21% vs. 1.73%, respectively) and mortality (0.59% vs. 0.91% for LR-M, 1.92% vs. 2.14% for CV-M and 1.04% vs. 1.14% for EHC-M, respectively). Life Years Gained (LYG) of Resmetirom-treated patients were 0.45 and 0.63 in MASLD patients with F2 and F3 fibrosis, respectively, and the model was sensitive to changes in Resmetirom efficacy and transition probabilities. Resmetirom decreases the 5-year and lifetime Markov-model estimated risk of CC, DC, HCC and liver-related mortality in patients with MASLD and F2 or F3 fibrosis.

Cost-utility analysis of add-on Qili Qiangxin capsules in chronic heart failure with reduced ejection fraction in China.

The study aimed to analyse the cost-utility of Chinese patent medicine Qili Qiangxin (QLQX) capsules in heart failure with a reduced ejection fraction from the healthcare payer's perspective. From the perspective of the healthcare payer, a Markov model was established to estimate the cost-utility of adding QLQX capsules to standard treatment versus standard treatment. A 19-year lifetime horizon was chosen with a 3-monthcycle in the base case analysis. The discount rate of cost and utility is 5%. Total costs and quality-adjusted life years (QALYs) for QLQX and standard treatment were simulated over a 19-year lifetime horizon by the Markov model using TreeAge Pro 2022. The incremental cost-utility ratio (ICUR) was compared with the willingness-to-pay thresholds (the GDP per capita). The one-way sensitivity analysis and probability sensitivity analysis were conducted. Over a 19-year lifetime horizon, the mean total costs in the QLQX group and standard treatment group were 56151.75 CNY and 30099.69 CNY, respectively. The QALYs in the QLQX group were also greater than those in the standard treatment group (4.63 QALYs vs. 4.17 QALYs). The ICUR was 57381.85 CNY per QALY, which was lower than the willingness-to-pay threshold (89358 CNY). The one-way and probability sensitivity analyses showed that the results were robust. The inputs with the largest impact on ICUR were the cardiovascular mortality in both groups. At a willingness-to-pay threshold of 89358 CNY, adding QLQX capsules to standard treatment was preferred over standard treatment alone in 51.10% of the 1000 PSA samples. This cost-utility analysis suggested that adding QLQX capsules seems to be cost-effective of heart failure with a reduced ejection fraction patients from the healthcare payer's perspective in China. Future studies of QLQX capsules based on different economic systems and medical environments were also needed.