Application of discrete event simulation model in analysis on cost-effectiveness of epidemiology screening / 中华流行病学杂志

Discrete event simulation (DES) model is based on individual data, by which discrete events over time are simulated to reflect disease progression. The effects of individual characteristics on disease progression could be considered in the DES model. Moreover, unlike state-transition models, DES model without setting of fixed cycle can contribute to more accurate estimation of event time, especially in the evaluation of the long-term effectiveness of screening strategies for complex diseases in which time dimension needs to be considered. This article introduces the general principles, construction steps, analytic methods and other relevant issues of the DES model. Based on a research case of estimating the cost-effectiveness of screening for abdominal aortic aneurysms in women aged 65 years and above in the United Kingdom, key points in applications of the DES model in analysis on effectiveness of complex disease screening are discussed in detail, including model construction and analysis and interpretation of the results. DES model can predict occurring time of discrete events accurately by establishing the distribution function of their occurring time and is increasingly used to evaluate the screening strategies for complex diseases in which time dimension needs to be considered. In the construction of DES model, it is necessary to pay close attention to the clear presentation of model structure and simulation process and follow the relevant reporting specification to conduct cost-effectiveness analysis to ensure the transparency and repeatability of the research.

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.

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.

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.

Influence of Yuanzhisan Containing Ginseng Radix et Rhizoma or Codonopsis Radix on Memory Disorder / 中国实验方剂学杂志

Objective:To explore the effects of Yuanzhisan （YZS） containing Ginseng Radix et Rhizoma （YZSR） or Codonopsis Radix （YZSD） on memory disorder based on network and experimental pharmacology. Method:The active components and targets of YZS were retrieved from the component database and literature， and the targets of memory disorder from the disease databases. The intersection targets revealed by Veen diagram were subjected to pathway analysis. The common active components of YZSR and YZSD were molecularly docked onto the core targets. Scopolamine hydrobromide was used to establish the memory disorder model， which was employed in the behavioral experiments for evaluating the effect of YZSR and YZSD on memory disorder. Result:There existed 33 active components for Ginseng Radix et Rhizoma and 31 for Codonopsis Radix， with four common active components and 380 common targets. YZSR contained 85 active components and 790 drug targets， and YZSD 81 active components and 781 drug targets. The mapping of 425 memory disorder targets with those of YZSD and YZSD yielded 133 and 130 intersection targets， respectively. The metabolic pathways involved calcium ion signaling pathway， hypoxia-inducible factor-1 （HIF-1） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， etc. As revealed by molecular docking， the binding energy of common active components to the targets was negative， and the binding effect of frutinone A was the best. Behavioral experiment results showed that both YZSR and YZSD alleviated the memory disorder. In the step-down test， the number of errors in the YZSD group was significant lower than that in the model group （<italic>P</italic><0.01）. In Morris water maze test， the movement distance of the YZSD group was remarkably shortened in comparison with that of the model group （<italic>P</italic><0.05）. In the open field test， the movement distances of both the YZSR and YZSD group were shortened in contrast to that in the normal group （<italic>P</italic><0.05）. Conclusion:YZS had a certain effect on memory disorder. There are similarities and differences between YZSR and YZSD in the treatment of memory disorder.

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.

Expression of two subtype molecules of CD133 in childhood with B linage acute lymphoblastic leukemia and its clinical significance / 中国实验血液学杂志

This study was to explore the expression of two subtype molecules of CD133 and its relationship with clinical prognostic factors in childhood with B linage acute lymphoblastic leukemia (B-ALL) at initial diagnosis and the 33rd day of induction chemotherapy. Expression of CD133-1 and CD133-2 in 48 cases of B-ALL and 25 cases at initial diagnosis and the 33rd day of treatment was detected by flow cytometry. Minimal residual disease (MRD) of B-ALL at 33rd day was evaluated by flow cytometry. The results indicated that the expression of CD133-1 was positive in 18 cases (37.5%), and expression of CD133-2 in 30 cases (62.5%) was positive from 48 cases with newly diagnosed ALL (P < 0.05). At 33rd day of treatment, expression of CD133-1 in 2 cases (8.0%) from 25 cases was positive, and expression of CD133-2 in 23 cases (92.0%) was positive (P < 0.05). After induction chemotherapy in B-ALL, the expression of CD133-1 decreased significantly, but still higher than that in the normal control group. Compared to expression of CD133-1, expression of CD133-2 decreased slowly. It is concluded that there is no relations among expression of CD133 and sex, age, white blood cell count, percentage of bone marrow blast cells, FAB subtype, cytogenetics, leukemia fusion gene, risk stratification and complete remission rate in childhood B-ALL. The positive expression rates and levels of CD133-2 are higher than those of CD133-1 in B-ALL. There is no statistical correlation between expression of CD133 and CD34 in B-ALL. The expression of CD133-2 is significantly related to the level of MRD.

Analysis of long tubular bone fracture healing in 37 patients with osteofluorosis / 中国地方病学杂志

Objective To study the correlations between bone fracture types and healing time in patients with osteofluorosis. Methods Thirty-seven patients with osteefluorosis and long tubular bone fracture were diagnosed in accordance with radiogram retrospectively. The fractures were divided into two groups: sclerotic and osteoporotic. Twenty four fractured patients with non osteofluorosis were included in the study as controls. All of the patients had operation(open reduction and nickelclad internal fixation). Fracture healing in patients with sclerotic and osteoporotic groups was compared with the control group after operation. Results There were notable differenees(F=4.30,P< 0.05) in term of fracture healing time among the three groups [sclerotic group:(18.4±5.3)weeks; osteoporotic group: (24.5±5.1)weeks; control group: (17.6±3.8)weeks]. Notably, there were significant differences between the osteoporotic and control groups(q=2.34,P<0.05), and between sclerotic and osteoporotic gronps(q=2.51, P<0.05). The healing time of the osteoporotic group was longer than that of sclerotic group. The constituent ratios of fracture healing in sclerotic, osteoporotic and control groups were 73.1% (19/26) ,54.5% (6/11),75.0% (18/24) respectively, and the differences among the three groups were statistically significant(X2=3.67,P<0.05). The healing rate of the osteoporotic group was lower than that of sclerotic and control groups(X2=3.12, 3.36, all P< 0.05). The constituent ratios of healing in the sclerotic, osteoporotic and control groups were 26.9% (7/26),45.5% (5/11),25.0%(6/24), respectively, and there differences among the three groups were statistically significant (X2=4.07 ,P<0.05). The delayed healing rate of the osteoperotic group was higher than those of the sclerotic and control groups(X2= 3.87,3.95, all P<0.05). Conclusions Fracture healing time of osteoporotic osteofluorosis after fracture is longer than normal, and the cause might be the loss of bone mass.

Molecular biological study of glycoprotein IX gene defect in Bernard-Soulier syndrome / 中华血液学杂志

<p><b>OBJECTIVE</b>To identify a mutation G2113-->A in the glycoprotein (GP)IX gene associated with Bernard-Soulier syndrome (BSS) and to investigate BSS pathogenesis.</p><p><b>METHODS</b>Allele-specific restriction enzyme was used to analyze the samples of patient, her mother, her brother and 40 healthy volunteers. Site-directed mutagenesis was performed to construct a expression vector PD-IXG2113A harboring the mutation G2113-->A. Chinese hamster ovary (CHO) cells were transiently cotransfected with plasmids harboring the entire coding region of GPIbalpha, GPIbeta and GPIX or mutant GPIX, respectively. Expression of GPIbalpha and GPIX in transfected CHO cells were analysed with flow cytometer. GPIbalpha and GPIX in the cytoplasma of transfected CHO cells were analysed by immunostaining and Western blotting.</p><p><b>RESULTS</b>The patient was found to be homozygosity of the substitution, her mother and her brother be heterozygous. Expressions of GPIbalpha and GPIX in mutant CHO cells were remarkably reduced, but abundant in the cytoplasma.</p><p><b>CONCLUSION</b>The mutation of Ala139(GCC)-->Thr(ACC) in the GPIX did not affect synthesis and assembly of GPIb/IX complex but influence its anchoring and expression on the cell surface, which was responsible for BSS.</p>