Pharmacoeconomics of ivabradine in the treatment of CHF in the context of “Quadruple Therapy” / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of ivabradine in the treatment of chronic heart failure （CHF） in the context of “Quadruple Therapy” from the perspective of the health system. METHODS Based on real-world cohort data， the Markov model was constructed according to the natural progression of CHF， with a cycle time of 3 months， a study timeframe of 20 years， and a discount rate of 5%. Using quality-adjusted life year （QALY） and incremental cost-effectiveness ratios （ICER） as the output indexes， the cost-utility analysis was used to evaluate the cost-effectiveness of ivabradine in combination with the “Quadruple Therapy” regimen， compared with the “Quadruple Therapy” regimen for the treatment of CHF， and the robustness of the results of the base analysis was verified by univariate sensitivity analysis and probabilistic sensitivity analysis. RESULTS The results of the base analysis showed that the ICER of ivabradine combined with the “Quadruple Therapy” regimen was 165 065.54 yuan/QALY， compared with the “Quadruple Therapy” regimen， which was lower than the willingness-to-pay （WTP） threshold （257 094 yuan/QALY） based on 3 times of China’s gross domestic product （GDP） per capita in 2022. The results of the univariate sensitivity analysis showed that the discount rate had the greatest impact on the robustness of the model. The probabilistic sensitivity analysis showed that the probability that the ivabradine combined with the “Quadruple Therapy” regimen was cost-effective under the WTP threshold in this study was 59.50%. CONCLUSIONS When using 3 times China’s 2022 GDP per capita （257 094 yuan/ QALY） as the WTP threshold， the combination of ivabradine and the “Quadruple Therapy” regimen for treating CHF is cost- effective.

Custo-utilidade da utilização de teste farmacogenético como guia para o tratamento de depressão sob a perspectiva do Sistema de Saúde Suplementar / Cost-utility of pharmacogenetic testing as a guide for the treatment of depression from the Brazilian Supplementary Health System perspective

Objetivo: Desenvolver uma análise de custo-utilidade da implementação do teste farmacogenético como uma ferramenta adicional para orientar a escolha do melhor tratamento medicamentoso para indivíduos com depressão. Métodos: Para a realização desta análise, criou-se um modelo analítico de decisão baseado em um modelo de Markov. A avaliação foi realizada sob a perspectiva do Sistema de Saúde Suplementar brasileiro, com horizonte temporal de 10 anos, incluindo custos médicos diretos e custos da tecnologia utilizada, além de ter como comparador o tratamento empírico tradicional para a depressão. As probabilidades de transição foram obtidas por meio de análise da literatura disponível. Também foram realizadas análises de sensibilidade probabilística e univariada. Adicionalmente, foi realizada uma avaliação sob a perspectiva da sociedade, incluindo os custos de tratamento medicamentoso realizados pelos pacientes. Resultados: De acordo com a análise realizada, o emprego do teste farmacogenético como guia do tratamento para depressão mostrou-se favorável, proporcionando economia de -R$ 3.439,97 por paciente e aumento de 0,39 QALY ao longo do horizonte temporal. Assim, evidencia-se uma economia significativa a favor do teste farmacogenético, correspondendo a -R$ 8.776,78 por QALY salvo. Além disso, a robustez do modelo foi comprovada por meio das análises de sensibilidade. No cenário sob perspectiva da sociedade, o resultado foi ainda mais favorável, proporcionando economia de -R$ 9.381,49 por paciente e aumento de 0,39 QALY, correspondendo a -R$ 23.936,05 por QALY salvo. Conclusão: Os resultados encontrados neste estudo demonstraram que o uso de testes farmacogenéticos no tratamento da depressão é economicamente vantajoso, com aumento no valor de QALY e redução nos custos médicos diretos, em comparação ao tratamento empírico tradicional. Essa descoberta alinha-se à tendência atual de personalização no cuidado da saúde mental, sugerindo implicações práticas na reavaliação de protocolos, com potencial incorporação dos testes farmacogenéticos como padrão de cuidado.

Objective: To evaluate the cost-utility of pharmacogenetic testing incorporation as an additional tool in guiding the selection of optimal drug treatments for individuals with depression. Methods: A decision analytical model was created based on the Markov model for this analysis. The evaluation was conducted from the perspective of the Brazilian Supplementary Health System, with a time horizon of 10 years. The study included direct medical and technology costs and a comparison with traditional empirical treatment for depression was performed. Transition probabilities were derived from an analysis of available literature. Probabilistic and univariate sensitivity analyses were also carried out. Additionally, an evaluation was conducted from the perspective of Society, including the costs of drug treatment carried out by patients. Results: The application of pharmacogenetic testing as a guide for depression treatment demonstrated favorable outcomes, yielding savings of -R$ 3,439.97 per patient and an increase of 0.39 QALY over the specified time frame. Thus, significant savings were evident, corresponding to -R$ 8,776.78 per QALY saved. The sensitivity analyses confirmed the model's robustness. In the Society's perspective scenario, the outcome was even more favorable, resulting in savings of -R$ 9,381.49 per patient and a 0.39 increase in QALYs, equivalent to -R$ 23,936.05 per QALY saved. Conclusion: The study findings reveal that incorporating harmacogenetic tests in depression treatment offers economic benefits, evidenced by an increase in QALY value and a decrease in direct medical costs compared to conventional empirical treatment. This aligns with the ongoing trend towards personalized mental health care, implying practical considerations for protocol reassessment and the possible integration of pharmacogenetic tests as a standard of care.

Comparison of aspirin treatment strategies for primary prevention of cardiovascular diseases: A decision-analytic Markov modelling study / 北京大学学报(医学版)

OBJECTIVE@#To compare the expected population impact of benefit and risk of aspirin treatment strategies for the primary prevention of cardiovascular diseases recommended by different guidelines in the Chinese Electronic Health Records Research in Yinzhou (CHERRY) study.@*METHODS@#A decision-analytic Markov model was used to simulate and compare different strategies of aspirin treatment, including: Strategy ①: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk, recommended by the 2020 Chinese Guideline on the Primary Prevention of Cardiovascular Diseases; Strategy ②: Aspirin treatment for Chinese adults aged 40-59 years with a high 10-year cardiovascular risk, recommended by the 2022 United States Preventive Services Task Force Recommendation Statement on Aspirin Use to Prevent Cardiovascular Disease; Strategy ③: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk and blood pressure well-controlled (< 150/90 mmHg), recommended by the 2019 Guideline on the Assessment and Management of Cardio-vascular Risk in China. The high 10-year cardiovascular risk was defined as the 10-year predicted risk over 10% based on the 2019 World Health Organization non-laboratory model. The Markov model simulated different strategies for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Quality-adjusted life year (QALY) and the number needed to treat (NNT) for each ischemic event (including myocardial infarction and ischemic stroke) were calculated to assess the effectiveness of the different strategies. The number needed to harm (NNH) for each bleeding event (including hemorrhagic stroke and gastrointestinal bleeding) was calculated to assess the safety. The NNT for each net benefit (i.e., the difference of the number of ischemic events could be prevented and the number of bleeding events would be added) was also calculated. One-way sensitivity analysis on the uncertainty of the incidence rate of cardiovascular diseases and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted.@*RESULTS@#A total of 212 153 Chinese adults, were included in this study. The number of people who were recommended for aspirin treatment Strategies ①-③ was 34 235, 2 813, and 25 111, respectively. The Strategy ③ could gain the most QALY of 403 [95% uncertainty interval (UI): 222-511] years. Compared with Strategy ①, Strategy ③ had similar efficiency but better safety, with the extra NNT of 4 (95%UI: 3-4) and NNH of 39 (95%UI: 19-132). The NNT per net benefit was 131 (95%UI: 102-239) for Strategy ①, 256 (95%UI: 181-737) for Strategy ②, and 132 (95%UI: 104-232) for Strategy ③, making Strategy ③ the most favorable option with a better QALY and safety, along with similar efficiency in terms of net benefit. The results were consistent in the sensitivity analyses.@*CONCLUSION@#The aspirin treatment strategies recommended by the updated guidelines on the primary prevention of cardiovascular diseases showed a net benefit for high-risk Chinese adults from developed areas. However, to balance effectiveness and safety, aspirin is suggested to be used for primary prevention of cardiovascular diseases with consideration for blood pressure control, resulting in better intervention efficiency.

Cost-effectiveness of regorafenib for hepatocellular carcinoma after failure of sorafenib / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of regorafenib in the treatment of hepatocellular carcinoma after failure of sorafenib from the perspective of Chinese health system. METHODS Based on a phase Ⅲ trial（RESORCE）， the partition survival model （PSM） and Markov model were constructed. The cycle was set as four weeks， the duration of the study lasted for lifetime， the annual discount rate was 5%. Drug cost data was obtained from yaozhi.com， other cost data were obtained from Anhui Provincial Medical Insurance Bureau and related literature， and utility values were obtained from literature. The incremental cost-effectiveness ratio （ICER） was used as the evaluation index， and the value of willingness to pay （WTP） was three times of China’s gross domestic product （GDP） per capita in 2022； one-way sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the basic analysis results. RESULTS The incremental cost of regorafenib group versus placebo group in PSM and Markov model was 112 116.95 yuan and 96 617.19 yuan， respectively. The incremental effectiveness was 0.31 QALYs and 0.32 QALYs， respectively. The ICERs were 360 751.01 yuan/QALY and 301 114.45 yuan/QALY， which were both greater than the value of WTP； regorafenib was not cost-effective. Results of one-way sensitivity analysis showed that the utility of progression-free survival and progressive disease， the unit cost of regorafenib had the greatest influence on the results， but ICER was always greater than the WTP within the floating range of each parameter. Under the WTP of 3 times China’s per capita GDP in 2022， the probabilities of regorafenib with cost-effectiveness were 0.8% （PSM） and 11.4% （Markov）. CONCLUSIONS Under the WTP of 3 times the per capita GDP of China， regorafenib is not cost-effective in the treatment of hepatocellular carcinoma after failure of sorafenib treatment， compared with placebo.

Study on pharmacoeconomic evaluation of vericiguat in the treatment of heart failure with reduced ejection fraction / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of vericiguat combined with standard treatment in the treatment of heart failure with reduced ejection fraction （HFrEF）. METHODS Based on the results of the VICTORIA trial and related literature， a three-state （including stable state of heart failure， hospitalized state of heart failure and death state） Markov model was constructed. The cycle length was 1 month， the time horizon was 20 years， the discount rate was 5%， and one time China’s per capita gross domestic product （GDP） in 2021 was the willing-to-pay （WTP） threshold. Cost-utility analysis was performed to evaluate the cost-effectiveness of vericiguat combined with standard treatment in the treatment of HFrEF. The output indicators included quality-adjusted life year （QALY） and incremental cost-effectiveness ratio （ICER）. The robustness of the results of the basic analysis was verified by one-way sensitivity analysis and probability sensitivity analysis. RESULTS The ICER of vericiguat combined with the standard treatment plan compared to the standard treatment plan alone was 444 341.95 yuan/QALY， which was more than WTP of this study （80 976 yuan/QALY）. One-way sensitivity analyses showed that the probability of cardiovascular death in both groups was the main influencing parameter for the robustness of the model， but they had little influence on the results of the basic analysis. The probabilistic sensitivity analysis displayed that under the WTP threshold of this study， the possibility of vericiguat combined with the standard treatment plan being more cost-effective was 2.6%. CONCLUSIONS Compared with the standard treatment plan， vericiguat combined with the standard treatment plan is not cost-effective in patients with HFrEF.

Estrutura familiar e dinâmica educacional entre gerações / Family structure and educational dynamics between generations / Estructura familiar y dinámica educativa entre generaciones

O presente estudo busca identificar o impacto da estrutura familiar (biparentais e uniparentais) sobre a dinâmica educacional intergeracional e a acumulação de capital humano. Foram utilizados os microdados da Pesquisa Nacional por Amostra de Domicílio (PNAD) de 2014. A dinâmica educacional intergeracional foi analisada a partir de matrizes de transição e de processos de Markov. As diferenças de acumulação de capital humano entre as categorias de estruturas familiares foram investigadas a partir da decomposição de Blinder-Oaxaca. Os resultados indicam que ser dependente, do sexo feminino e residir na zona urbana são características associadas a uma maior mobilidade intergeracional de educação. O Nordeste se destaca como a região com menor mobilidade intergeracional educacional. A decomposição de Blinder-Oaxaca indica que, em média, as famílias uniparentais chefiadas por uma mulher possuem 0,5 ano de estudo a mais do que as uniparentais chefiadas pelo pai. Cerca de 74,2% dessa diferença é explicada pelo modelo estimado e a parte não explicada não possui significância estatística. Os resultados sugerem que a estrutura familiar afeta a dinâmica intergeracional de educação e a acumulação de capital humano dos indivíduos.

Objective. The present study seeks to identify the impact of the family structure (two-parent and one-parent) on the intergenerational educational dynamics and the accumulation of human capital. Method. The microdata from the National Household Sampling Survey (PNAD) of 2014 were used. The intergenerational educational dynamics was analyzed based on transition matrices and Markov processes. Differences in human capital accumulation between categories of family structures were investigated based on the Blinder-Oaxaca decomposition. Results. Results indicate that being dependent, female and living in the urban area are characteristics associated with greater intergenerational education mobility. The Northeast region stands out as the region with the lowest educational intergenerational mobility. The decomposition of Blinder-Oaxaca indicates that, on average, single-parent families headed by a woman have 0.5 years of study more than single-parent families headed by a father. About 74.2% of this difference is explained by the estimated model and the unexplained part has no statistical significance. Conclusion. Results suggest that the family structure affects the intergenerational dynamics of education and the accumulation of human capital of individuals.

Objetivo. El presente estudio busca identificar el impacto de la estructura familiar (biparental y monoparental) sobre la dinámica educativa intergeneracional y la acumulación de capital humano. Método. Se utilizaron los microdatos de la Encuesta Nacional de Muestreo de Hogares (PNAD) de 2014. Se analizó la dinámica educativa intergeneracional a partir de matrices de transición y procesos de Markov. Las diferencias en la acumulación de capital humano entre categorías de estructuras familiares se investigaron con base en la descomposición Blinder-Oaxaca. Resultados. Los resultados indican que ser dependiente, ser mujer y vivir en el área urbana son características asociadas a una mayor movilidad educativa intergeneracional. La nordestina se destaca como la región con menor movilidad educativa intergeneracional. La descomposición de Blinder-Oaxaca indica que, en promedio, las familias monoparentales encabezadas por una mujer tienen 0,5 años de estudio más que las familias monoparentales encabezadas por el padre. Aproximadamente el 74,2 % de esta diferencia se explica por el modelo estimado y la parte inexplicada no tiene significación estadística. Conclusión. Los resultados sugieren que la estructura familiar afecta la dinámica intergeneracional de la educación y la acumulación de capital humano de los individuos.

A pace recognition method for exoskeleton wearers based on support vector machine-hidden Markov model / 生物医学工程学杂志

In order to improve the motion fluency and coordination of lower extremity exoskeleton robots and wearers, a pace recognition method of exoskeleton wearer is proposed base on inertial sensors. Firstly, the triaxial acceleration and triaxial angular velocity signals at the thigh and calf were collected by inertial sensors. Then the signal segment of 0.5 seconds before the current time was extracted by the time window method. And the Fourier transform coefficients in the frequency domain signal were used as eigenvalues. Then the support vector machine (SVM) and hidden Markov model (HMM) were combined as a classification model, which was trained and tested for pace recognition. Finally, the pace change rule and the human-machine interaction force were combined in this model and the current pace was predicted by the model. The experimental results showed that the pace intention of the lower extremity exoskeleton wearer could be effectively identified by the method proposed in this article. And the recognition rate of the seven pace patterns could reach 92.14%. It provides a new way for the smooth control of the exoskeleton.

Cost-utility analysis of tislelizumab in the second -line treatment of advanced or metastatic esophageal squamous cell carcinoma / 中国药房

OBJECTIVE To evaluate the cost -effectiveness of tislelizumab in the second -line treatment of advanced or metastatic esophageal squamous cell carcinoma （ESCC）in China .METHODS A three -state Markov model was constructed to assess the cost -effectiveness of tislelizumab versus chemotherapy in the second -line treatment of advanced or metastatic ESCC and programmed death receptor 1（PD-L1）positive patients . The cycle length of the model was 1 month，and the time horizon of the model was set as 10 years. The discount rate of cost and utility was 5%. One-way sensitivity analysis ，probability sensitivity analysis and scenario analysis were used to verify the robustness of the base -case analysis results . RESULTS The results of the base-case analysis showed that compared with chemotherapy ，the incremental cost -effectiveness ratio （ICER）of tislelizumab in the second-line treatment of advanced or metastatic ESCC and PD -L1-positive patients were 26 864.01 yuan/QALY and 37 510.07 yuan/QALY，respectively，which was much lower than 1 time per capita gross domestic product （GDP）in 2021（80 976 yuan）. Results of scenario analysis showed that the ICER was less than 1 times per capita GDP ，regardless of the chemotherapy regimens（paclitaxel，docetaxel or irinotecan ）used. With the extension of the simulation time limit ，the ICER of tirelizumab regimen gradually decreased ，and the reduction rate gradually E-mail：lishunping@sdu.edu.cn decreased，but they were all less than 1 time China ’s per capita GDP in 2021. The results of the one -way sensitivity analysis showed that the 3 parameters with the most significant impact on the ICER were progression -free survival of tislelizumab group ，price of tislelizumab ，and the proportion of patients receiving follow-up treatment in the tislelizumab group . The results of the probability sensitivity analysis showed that the probability of tislelizumab with cost -effectiveness in the treatment of advanced or metastatic ESCC patients and PD -L1-positive patients were 99.09% and 99.94%，respectively，when using 3 times per capita GDP as the willingness -to-pay threshold . CONCLUSIONS Tislelizumab has economic advantages over chemotherapy alone in the second -line treatment of advanced or metastatic ESCC patients.

Effectiveness of different screening strategies for type 2 diabete on preventing cardiovascular diseases in a community-based Chinese population using a decision-analytic Markov model / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the effectiveness of different screening strategies for type 2 diabetes to prevent cardiovascular disease in a community-based Chinese population from economically developed areas based on the Chinese electronic health records research in Yinzhou (CHERRY) study.@*METHODS@#A Markov model was used to simulate different systematic diabetes screening strategies, including: (1) screening among Chinese adults aged 40-70 years recommended by the 2020 Chinese Guideline for the prevention and Treatment of Type 2 Diabetes (Strategy 1); (2) screening among Chinese adults aged 35 to 70 years recommended by the 2022 American Diabetes Association Standard of Medical Care in Diabetes (Strategy 2); and (3) screening among Chinese adults aged 35-70 years with overweight or obesity recommended by the 2021 United States Preventive Services Task Force Recommendation Statement on Screening for Prediabetes and Type 2 Diabetes (Strategy 3). According to the guidelines, individuals who were screened positively (fasting plasma glucose ≥ 7.0 mmol/L) would be introduced to intensive glycemic targets management (glycated hemoglobin < 7.0%).The Markov model simulated different screening scenarios for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Number of cardiovascular disease events or deaths could be prevented and number needed to screen (NNS) were calculated to compare the effectiveness of the different strategies. One-way sensitivity analysis on the sensitivity of screening methods and probabilistic sensitivity analysis on uncertainties of diabetes incidence, the sensitivity of screening methods, and intensive glycemic management effects were conducted.@*RESULTS@#Totally 289 245 Chinese adults aged 35-70 years without cardiovascular diseases or diagnosed diabetes at baseline were enrolled. In terms of the number of cardiovascular disease events could be prevented, Strategy 1 for systematic diabetes screening among the adults aged 35-70 years was 222 (95%UI: 180-264), Strategy 2 for systematic diabetes screening among the adults aged 40-70 years was 227 (95%UI: 185-271), and Strategy 3 for systematic diabetes screening among the adults aged 35-70 years with obesity or overweight (body mass index ≥ 24 kg/m2) was 131 (95%UI: 98-164), compared with opportunistic screening. NNS per cardiovascular disease event for the strategies 1, 2 and 3 were 1 184 (95%UI: 994-1 456), 1 274 (95%UI: 1 067-1 564) and 814 (95%UI: 649-1 091), respectively. Compared with Strategy 1, NNS per cardiovascular disease event for Strategy 2 increased by 90 (95%UI: -197-381) with similar effectiveness of cardiovascular prevention; however, NNS per cardiovascular disease event for Strategy 3 was reduced by 460 (95%UI: 185-724) in contrast to the Strategy 2, suggesting that the Strategy 3 was more efficient. The results were consistent in multiple sensitivity analyses.@*CONCLUSION@#Systematic screening for diabetes based on the latest guidelines in economically developed areas of China can reduce cardiovascular events and deaths. However, merely lowering the starting age of screening from 40 to 35 years seems ineffective for preventing cardiovascular disease, while screening strategy for Chinese adults aged 35-70 years with overweight or obesity is recommended to improve efficiency.

Effectiveness of statin treatment strategies for primary prevention of cardiovascular diseases in a community-based Chinese population: A decision-analytic Markov model / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the effectiveness of statin treatment strategies based on risk assessment for the primary prevention of cardiovascular diseases by the Western guidelines in a community-based Chinese population from economically developed areas using data from the Chinese electronic health records research in Yinzhou (CHERRY) study.@*METHODS@#A Markov model was used to evaluate the effectiveness of the following statin treatment strategies, including: (1) usual care without cardiovascular risk assessment(Strategy 0); (2) using the World Health Organization (WHO) non-laboratory-based risk charts with statin treatment for high-risk group (risk ≥ 20%) (Strategy 1); (3) using the WHO laboratory-based risk charts with statin treatment for high-risk group (risk ≥ 20%) (Strategy 2); and (4) using the Prediction for Atherosclerotic cardiovascular disease Risk in China (China-PAR) model with statin treatment for high-risk group (risk ≥ 10%, Strategy 3). According to the guidelines, adults in the medium-risk group received lifestyle intervention, and adults in the high-risk group received life-style intervention and statin treatment under these strategies. The Markov model simulated different strategies for ten years (cycles) using parameters from the CHERRY study, published data, meta-analyses and systematic reviews for Chinese. The number of cardiovascular events or deaths, as well as the number need to treat (NNT) with statin per cardiovascular event or death prevented, were calculated to compare the effectiveness of different strategies. One-way sensitivity analysis on the uncertainty of incidence rate of cardiovascular diseases, and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted.@*RESULTS@#Totally 225 811 Chinese adults aged 40-79 years without cardiovascular diseases at baseline were enrolled. In contrast to the usual care without risk assessment-based statin treatment strategy, Strategy 1 using the WHO non-laboratory-based risk charts could prevent 3 482 [95% uncertainty interval (UI): 2 110-4 661] cardiovascular events, Strategy 2 using the WHO laboratory-based risk charts could prevent 3 685 (95%UI: 2 255-4 912) events, and Strategy 3 using the China-PAR model could prevent 3 895 (95%UI: 2 396-5 181) events. NNTs with statin per cardiovascular event prevented were 22 (95%UI: 14-54), 21 (95%UI: 14-52), and 27 (95%UI: 17-67), respectively. Strategy 3 could prevent more cardiovascular events, while Strategies 1 and 2 required fewer numbers need to treat with statin per cardiovascular event prevented. The results were consistent in the sensitivity analyses.@*CONCLUSION@#The statin treatment strategies based on risk assessment for the primary prevention of cardiovascular diseases recommended by the Western guidelines could achieve substantive health benefits in adults from developed areas of China. Using the China-PAR model for cardiovascular risk assessment could prevent more cardiovascular diseases while using the WHO risk charts seems more efficient.

Research and Engineering Evaluation Practice of Medical Equipment Purchase Decision Model Based on Improved Markov Model / 中国医疗器械杂志

In view of the inherent drawbacks of traditional medical equipment procurement mode, a decision-making model of medical equipment procurement based on Improved Markov model is proposed and the engineering evaluation practice is carried out. The data pool of medical equipment procurement of big data level is constructed, the core constraint factors of medical equipment procurement are perceived by deep learning, the decision model of medical equipment procurement under multi-dimensional constraints is constructed, and the Improved Markov model is introduced, and the observable decision-making scheme of medical equipment procurement is given. The results show that the model can give the decision-making scheme of medical equipment procurement with global optimal attribute under multi-dimensional constraints. It has obvious advantages in the balance of long-term demand and immediate demand, the optimization of procurement decision-making scheme, and the accuracy of patient demand prediction in a long period.

A Gaussian mixture-hidden Markov model of human visual behavior / 生物医学工程学杂志

Vision is an important way for human beings to interact with the outside world and obtain information. In order to research human visual behavior under different conditions, this paper uses a Gaussian mixture-hidden Markov model (GMM-HMM) to model the scanpath, and proposes a new model optimization method, time-shifting segmentation (TSS). The TSS method can highlight the characteristics of the time dimension in the scanpath, improve the pattern recognition results, and enhance the stability of the model. In this paper, a linear discriminant analysis (LDA) method is used for multi-dimensional feature pattern recognition to evaluates the rationality and the accuracy of the proposed model. Four sets of comparative trials were carried out for the model evaluation. The first group applied the GMM-HMM to model the scanpath, and the average accuracy of the classification could reach 0.507, which is greater than the opportunity probability of three classification (0.333). The second set of trial applied TSS method, and the mean accuracy of classification was raised to 0.610. The third group combined GMM-HMM with TSS method, and the mean accuracy of classification reached 0.602, which was more stable than the second model. Finally, comparing the model analysis results with the saccade amplitude (SA) characteristics analysis results, the modeling analysis method is much better than the basic information analysis method. Via analyzing the characteristics of three types of tasks, the results show that the free viewing task have higher specificity value and a higher sensitivity to the cued object search task. In summary, the application of GMM-HMM model has a good performance in scanpath pattern recognition, and the introduction of TSS method can enhance the difference of scanpath characteristics. Especially for the recognition of the scanpath of search-type tasks, the model has better advantages. And it also provides a new solution for a single state eye movement sequence.

Pharmacoeconomic evaluation of Suhuang Zhike Capsules using Markov model for inpatients with acute exacerbation of chronic obstructive pulmonary disease / 中国中药杂志

To evaluate the economics of Suhuang Zhike Capsules in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) for inpatients. Based on the published clinical research data, cost-utility analysis was used in this study to evaluate the pharmacoeconomics of Suhuang Zhike Capsules in treatment of AECOPD inpatients from the perspective of medical insu-rance. The test group was treated with Suhuang Zhike Capsules combined with conventional Western medicine, and the control group was treated with conventional Western medicine alone. Treeage software was used to construct a pharmacoeconomic model and perform simulation analysis. The results showed that the cost and output of Suhuang Zhike Capsules combined with the conventional Western medicine were 60 010.18 yuan and 1.92 quality adjusted life year(QALYs), respectively in the simulated 3 years of disease treatment. The cost and output of the conventional Western medicine were 96 730.60 yuan and 1.90 QALYs respectively. Suhuang Zhike Capsules combined with conventional Western medicine required lower cost but achieved higher output, showing cost-utility advantages, so this drug combination was a plan with pharmacoeconomic advantages. The sensitivity analysis results showed that the conclusion was relatively stable. Based on the above results, it is believed that as compared with the conventional Western medicine, Suhuang Zhike Capsules combined with conventional Western medicine have lower cost and higher output for the treatment of AECOPD inpatients, and it is a treatment plan with pharmacoeconomic advantages.

Pharmacoeconomic evaluation of Shexiang Tongxin Dropping Pills combined with conventional Western medicine treatment for coronary heart disease by Markov model / 中国中药杂志

This research was to evaluate the economics of Shexiang Tongxin Dropping Pills combined with conventional therapy for patients with coronary heart disease(CHD) in Chinese medical environment. From the perspective of medical insurance, a Markov model was established in this study based on the results of Meta-analysis comparing the effectiveness and safety of Shexiang Tongxin Dripping Pills combined with conventional treatment and conventional treatment alone. The experimental group was treated with She-xiang Tongxin Dropping Pills combined with conventional Western medicine treatment, while the control group was treated with conventional Western medicine treatment alone. The cost-utility analysis and sensitivity analysis were performed for the two regimens using Treeage pro. After 30 cycles of model simulation, according to the results of Markov model, the total cost and health output were CNY 237 795.73 and 16.36 QALYs(the quality adjusted life years, QALYs), respectively for Shexiang Tongxin Dropping Pills combined with conventional Western medicine treatment, CNY 247 396.55 and 16.36 QALYs respectively for the conventional Western medicine treatment alone. Compared with the conventional treatment alone, the Shexiang Tongxin Dropping Pills combined with conventional treatment had lower long-term cost and higher health output, with advantages of cost-utility and pharmacoeconomic advantages. The sensitivity analysis results showed that the conclusion was relatively stable. Based on the above results, it is considered that compared with the conventional Western medicine alone, Shexiang Tongxin Dropping Pill combined with conventional Western medicine is a treatment regimen with pharmacoeconomic advantages for the treatment of CHD.

Cost-utility Analysis of the Pan-genotypic Direct-acting Antivirals in the Treatment of Chronic Hepatitis C Infection / 中国药房

OBJECTIVE：To evaluate the cost-utility of the pan-genotypic direct-acting antivirals （DAAs）in the treatment of patients with chronic hepatitis C infection ，and to provide pharmacoeconomic evidence for relevant health care decisions. METHODS：A Markov model was established from a societal perspective with newly diagnosed chronic hepatitis C patients in China as the target population ，and analyzed quality-adjusted life years （QALYs）and incremental cost-utility ratios （ICERs）of patients with chronic hepatitis C with sofosbuvir/velpatasvir ，glecaprevir/pibrentasvir，sofosbuvir+coblopasvir. Sensitivity analysis was used to verity the robustness of the results. RESULTS ：Glecaprevir/pibrentasvir increased QALYs by 0.002 1 and costs by 25 021 RMB，compared to sofosbuvir/velpatasvir ；its ICERs was 12 129 031 yuan/QALY（willingness to pay threshold was 70 892 yuan/QALY），which had no cost-utility ；glecaprevir/pibrentasvir need to cut down the price by 64.65％ to have cost-utility. Sofosbuvir+coblopasvir increased QALYs by 0.002 0 and saved costs by 515 yuan，so it was the optimal regimen which was cost-saving. Sensitivity analysis showed that SVR rates and drug prices were the most influential factors. The probability of having cost-utility for sofosbuvir+coblopasvir was higher than glecaprevir/pibrentasvir. CONCLUSIONS ：Glecaprevir/pibrentasvir need to reduce the price to achieve better affordability. Sofosbuvir+coblopasvir shows economical advantage.

Effectiveness of different screening strategies for cardiovascular diseases prevention in a community-based Chinese population: A decision-analytic Markov model / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the potential effectiveness of different screening strategies for cardiovascular diseases prevention in a community-based Chinese population from economically developed area of China.@*METHODS@#Totally 202 179 adults aged 40 to 74 years without cardiovascular diseases at baseline (January 1, 2010) were enrolled from the Chinese electronic health records research in Yinzhou (CHERRY) study. Three scenarios were considered: the screening strategy based on risk charts recommended by the 2020 Chinese guideline on the primary prevention of cardiovascular diseases in Chinese adults aged 40-74 years (Strategy 1); the screening strategy based on the prediction for atherosclerotic cardiovascular disease risk in China (China-PAR) models recommended by the 2019 Guideline on the assessment and management of cardiovascular risk in China in Chinese adults aged 40-74 years (Strategy 2); and the screening strategy based on the China-PAR models in Chinese adults aged 50-74 years (Strategy 3). According to the guidelines, individuals who were classified into medium- or high-risk groups after cardiovascular risk assessment by the corresponding strategies would be introduced to lifestyle intervention, while high-risk population would take medication in addition. Markov model was used to simulate different screening scenarios for 10 years (cycles), using parameters mainly from the CHERRY study, as well as published data, Meta-analyses and systematic reviews for Chinese populations. The life year gained, quality-adjusted life year (QALY) gained, number of cardiovascular disease events/deaths could be prevented and number needed to be screened (NNS) were calculated to compare the effectiveness between the different strategies. One-way sensitivity analysis on uncertainty of cardiovascular disease incidence rate and probabilistic sensitivity analysis on uncertainty of distributions for the hazard ratios were conducted.@*RESULTS@#Compared with non-screening strategy, QALYs gained were 1 433 [95% uncertainty interval (UI): 969-1 831], 1 401 (95%UI: 936-1 807), and 716 (95%UI: 265-1 111) for the Strategies 1, 2, and 3; and the NNS per QALY in the above strategies were 141 (95%UI: 110-209), 144 (95%UI: 112-216), and 198 (95%UI: 127-529), respectively. The Strategies 1 and 2 based on different guidelines showed similar effectiveness, while more benefits were found for screening using China-PAR models in adults aged 40-74 years than those aged 50-74 years. The results were consistent in the sensitivity analyses.@*CONCLUSION@#Screening for cardiovascular diseases in Chinese adults aged above 40 years seems effective in coastal developed areas of China, and the different screening strategies based on risk charts by the 2020 Chinese guideline on the primary prevention of cardiovascular diseases or China-PAR models by the 2019 Guideline on the assessment and management of cardiovascular risk in China may have similar effectiveness.

Symptoms of schizophrenia and regularity in treatment: a stochastic analysis

Background: The alarming rise of mental disorders worldwide stimulates the need to study them from a statistical viewpoint. Schizophrenia is one of the most prevalent mental illness which is characterised by various symptoms, the presence of a cluster of which leads to its diagnosis. Regular treatment leads to a remission of the illness which might relapse on discontinuity of medicines. There have been numerous epidemiological studies and clinical trials on the illness. However, schizophrenia also poses a challenge to statisticians in theorising and statistically modeling its different aspects. Aim: This is an attempt to study, by developing suitable stochastic models, the behaviour of the symptoms of schizophrenia manifested in a patient in relation to the successive visits to the doctor. Methods: The concepts of probability theory, structure functions, binomial distribution, Markov chain, and transition probabilities are the statistical tools used to model the medical facts regarding schizophrenia. Results: By developing probabilistic and stochastic models, a relationship between the number of symptoms at the time of diagnosis and the number of revisits to the doctor has been developed and thereby an important result regarding the expected number of symptoms present at a particular visit to the doctor has been established. A Markovian model studying the pattern of the symptoms in the course to recovery has been presented and its application in the behaviour of the symptoms of schizophrenia has been verified. Conclusions: It is expected that the above results might help doctors in planning out the treatment schedule in advance. It can also lead to a further study on cost benefit analysis of the treatment process.

Continuo ascenso de la prevalencia de diabetes mellitus en mujeres chilenas en edad fértil: proyección 2020-2039 de malformaciones congénitas por diabetes pregestacional / Cost-effectiveness of a diabetes detection program in childbearing women to prevent malformations

BACKGROUND: In Chile, in the next 20 years there will be an average number of 537,100 women of childbearing age with type 2 diabetes (T2DM). Half of these women, not knowing their diagnosis of diabetes will become pregnant with elevated glycosylated hemoglobin levels, increasing to 25% the risk of having offspring with congenital malformations. AIM: To calculate the cost-effectiveness of a diabetes detection strategy in women of childbearing age for the prevention of congenital malformations in the period 2020-2039. MATERIAL AND METHODS: The Markov stochastic model was used in two scenarios, namely A: No intervention and B: Intervention, detecting T2DM in Chilean women aged 15-49 years. We calculated the years of life lost due to premature death (YLL), years of life lost adjusted for disability (DALY) and total costs using American dollars (US$) of 2017, with a discount rate of 5%. RESULTS: In scenario A: 63,330 children with malformations would be born, YLLs and DALYs would be 800,750 and 1,544,775 respectively, and US$ 10,194,298,011 would be expended. In scenario B, these figures would be reduced in approximately 70% to 19,025 children born with malformations, YLLS and DALYs would be 40,539 and 464,033 respectively and US$ 3,354,321,968 would be expended. The costs of prevention would be US$ 6,590.94/malformation avoided, US$ 521.33/YLL avoided, and US$ 270.24/DALY avoided. CONCLUSIONS: In the context of an increasing prevalence of diabetes in women of childbearing age, our results suggest that the early detection of diabetes in Chilean women between 15 and 49 years of age, should be cost-effective to avoid an increase in congenital malformations for the next 20 years.

A new gene inventory of the ubiquitin and ubiquitin-like conjugation pathways in Giardia intestinalis

BACKGROUND Ubiquitin (Ub) and Ub-like proteins (Ub-L) are critical regulators of complex cellular processes such as the cell cycle, DNA repair, transcription, chromatin remodeling, signal translation, and protein degradation. Giardia intestinalis possesses an experimentally proven Ub-conjugation system; however, a limited number of enzymes involved in this process were identified using basic local alignment search tool (BLAST). This is due to the limitations of BLAST's ability to identify homologous functional regions when similarity between the sequences dips to < 30%. In addition Ub-Ls and their conjugating enzymes have not been fully elucidated in Giardia. OBJETIVE To identify the enzymes involved in the Ub and Ub-Ls conjugation processes using intelligent systems based on the hidden Markov models (HMMs). METHODS We performed an HMM search of functional Pfam domains found in the key enzymes of these pathways in Giardia's proteome. Each open reading frame identified was analysed by sequence homology, domain architecture, and transcription levels. FINDINGS We identified 118 genes, 106 of which corresponded to the ubiquitination process (Ub, E1, E2, E3, and DUB enzymes). The E3 ligase group was the largest group with 82 members; 71 of which harbored a characteristic RING domain. Four Ub-Ls were identified and the conjugation enzymes for NEDD8 and URM1 were described for first time. The 3D model for Ub-Ls displayed the β-grasp fold typical. Furthermore, our sequence analysis for the corresponding activating enzymes detected the essential motifs required for conjugation. MAIN CONCLUSIONS Our findings highlight the complexity of Giardia's Ub-conjugation system, which is drastically different from that previously reported, and provides evidence for the presence of NEDDylation and URMylation enzymes in the genome and transcriptome of G. intestinalis.

Segmentation of heart sound signals based on duration hidden Markov model / 生物医学工程学杂志

Heart sound segmentation is a key step before heart sound classification. It refers to the processing of the acquired heart sound signal that separates the cardiac cycle into systolic and diastolic, etc. To solve the accuracy limitation of heart sound segmentation without relying on electrocardiogram, an algorithm based on the duration hidden Markov model (DHMM) was proposed. Firstly, the heart sound samples were positionally labeled. Then autocorrelation estimation method was used to estimate cardiac cycle duration, and Gaussian mixture distribution was used to model the duration of sample-state. Next, the hidden Markov model (HMM) was optimized in the training set and the DHMM was established. Finally, the Viterbi algorithm was used to track back the state of heart sounds to obtain S