目的:观察甘草次酸对C57BL/6小鼠急性放射性肺损伤的保护效应。方法:成年C57BL/6雌性小鼠90只,随机数字表法分为3组,每组30只:空白对照组:未照射+生理盐水10 m L/kg灌胃;单纯照射组:照射+生理盐水10 m L/kg灌胃;甘草次酸组:照射+甘草次...目的:观察甘草次酸对C57BL/6小鼠急性放射性肺损伤的保护效应。方法:成年C57BL/6雌性小鼠90只,随机数字表法分为3组,每组30只:空白对照组:未照射+生理盐水10 m L/kg灌胃;单纯照射组:照射+生理盐水10 m L/kg灌胃;甘草次酸组:照射+甘草次酸40 mg/kg灌胃。单纯照射组和甘草次酸组小鼠予6MV-X线12Gy全肺单次照射。照射前30 min给药一次,以后1次/d连续7 d后改为隔日给药,直至照射后一个月。照射后第2、17、30天随机从各组分别选取10只小鼠处死。取双侧肺组织行HE染色、Masson染色观察肺组织形态变化。结果:空白对照组小鼠肺组织结构正常。单纯照射组小鼠肺组织在照射后第2天、17天以渗出为主,肺泡腔及间隔可见渗出、充血,伴有炎症细胞的浸润。照射后第30天,肺泡壁间隔增宽、肺泡结构变形、炎性细胞浸润,并可见胶原纤维沉积。甘草次酸组在不同时间点,肺泡炎及胶原沉积的情况均较单纯照射组改善,任一时间点两组之间差异有统计学意义(P<0.05)。结论:甘草次酸能够改善急性放射性肺损伤小鼠的一般情况,减轻肺组织炎症反应及改善胶原沉积。展开更多
Gefitinib,erlotinib,afatinib and osimertinib have been recommended as the first-line treatment for epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC),whereas no studies have comp...Gefitinib,erlotinib,afatinib and osimertinib have been recommended as the first-line treatment for epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC),whereas no studies have compared the cost-effectiveness of these four tyrosine kinase inhibitors(TKIs)simultaneously in China.In the present study,we aimed to estimate the cost-effectiveness of erlotinib,gefitinib,afatinib and osimertinib for untreated EGFR-mutated advanced NSCLC.A Markov model was constructed to compare the 10-year impact of four TKIs for patients with treatment-naive EGFR-mutated advanced NSCLC from the perspective of the Chinese medical system.Clinical data and utility values were derived from published literature,and costs were obtained from Chinese official websites.The primary output indicator was the incremental cost-effectiveness ratio(ICER).Sensitivity analyses were performed to test the robustness of the model.We found that afatinib was estimated to spend the lowest cost with minimum life-years(LYs),while osimertinib was the most expensive regimen with maximum LYs.The ICER of gefitinib versus afatinib was$732/quality-adjusted life-year(QALY),which was less than the willingness-to-pay(WTP)of$29382/QALY.Compared with gefitinib,erlotinib yielded a higher cost and a shorter lifetime,hence it was identified as a dominated strategy.Then,osimertinib was compared to gefitinib,which produced an ICER of$71330/QALY,exceeding the WTP.It suggested that gefitinib was the most cost-effective regimen as the first-line treatment for EGFR-mutated advanced NSCLC.Decreasing the osimertinib price or increasing the WTP threshold to$68558/QALY might enhance the favorability of the outcome,by which osimertinib might become more cost-effective.One-way sensitivity analysis manifested that the model was robust.展开更多
In the present study, we aimed to develop a population pharmacokinetics(PPK) model of vancomycin(VCM) and propose the individualised dosage regimen for Chinese elderly patients. The data were collected prospectively f...In the present study, we aimed to develop a population pharmacokinetics(PPK) model of vancomycin(VCM) and propose the individualised dosage regimen for Chinese elderly patients. The data were collected prospectively from Chinese elderly patients receiving VCM therapy. Steady-state trough concentrations of VCM were determined using an enzyme-multiplied immunoassay. Patients’ sex, age, body weight, concomitant medications, infection type, and laboratory findings were recorded. The PPK model was developed using nonlinear mixed-effects model software. Moreover, we used Monte Carlo simulations to develop an initial dosage regimen targeting various VCM through concentration ranges based on the final model. We found that VCM clearance(CL) was significantly influenced by post-craniotomy meningitis(PCM) and glomerular filtration rate in elderly patients. Additionally, a new dosage regimen was proposed to individualise VCM regimen for PCM and non-PCM elderly patients. A PPK model was established to estimate the individual VCM CL for elderly patients, which could be applied for individualising doses in the target population.展开更多
Lung cancer is the most widespread type of cancer and the primary cause of cancer-related death in the world.In this study,we aimed to analyze the cost-effectiveness of second-line chemotherapy strategies based on gem...Lung cancer is the most widespread type of cancer and the primary cause of cancer-related death in the world.In this study,we aimed to analyze the cost-effectiveness of second-line chemotherapy strategies based on gemcitabine,pemetrexed,and docetaxel for advanced non-squamous non-small cell lung cancer patients in China.A Markov model based on three states,progression-free survival,progressed survival and death,was constructed to simulate the progression of the disease in a 6-year horizon.Sensitivity analysis was performed to evaluate the robustness of the model.The primary outcome of the model was the incremental cost-effectiveness ratio at a willingness-to-pay threshold of 3×per capita GDP of China in 2018($29383).The baseline model results showed that the quality-adjusted life years over the course of the disease associated with second-line chemotherapy strategies were 0.233,0.417 and 0.272 for gemcitabine,pemetrexed and docetaxel,respectively,and the corresponding total costs were$5321.02,$12143.94,and$9479.42.Gemcitabine,pemetrexed and docetaxel resulted in the incremental cost-effectiveness ratios of$37081.09 and$106625.64 per quality-adjusted life year gained.The incremental cost-effectiveness ratio of pemetrexed and docetaxel compared with gemcitabine exceeded the willingness-to-pay threshold.One-way sensitivity analysis showed that the utility value of gemcitabine in the progressed survival state was the most influential parameter.展开更多
文摘目的:观察甘草次酸对C57BL/6小鼠急性放射性肺损伤的保护效应。方法:成年C57BL/6雌性小鼠90只,随机数字表法分为3组,每组30只:空白对照组:未照射+生理盐水10 m L/kg灌胃;单纯照射组:照射+生理盐水10 m L/kg灌胃;甘草次酸组:照射+甘草次酸40 mg/kg灌胃。单纯照射组和甘草次酸组小鼠予6MV-X线12Gy全肺单次照射。照射前30 min给药一次,以后1次/d连续7 d后改为隔日给药,直至照射后一个月。照射后第2、17、30天随机从各组分别选取10只小鼠处死。取双侧肺组织行HE染色、Masson染色观察肺组织形态变化。结果:空白对照组小鼠肺组织结构正常。单纯照射组小鼠肺组织在照射后第2天、17天以渗出为主,肺泡腔及间隔可见渗出、充血,伴有炎症细胞的浸润。照射后第30天,肺泡壁间隔增宽、肺泡结构变形、炎性细胞浸润,并可见胶原纤维沉积。甘草次酸组在不同时间点,肺泡炎及胶原沉积的情况均较单纯照射组改善,任一时间点两组之间差异有统计学意义(P<0.05)。结论:甘草次酸能够改善急性放射性肺损伤小鼠的一般情况,减轻肺组织炎症反应及改善胶原沉积。
文摘Gefitinib,erlotinib,afatinib and osimertinib have been recommended as the first-line treatment for epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC),whereas no studies have compared the cost-effectiveness of these four tyrosine kinase inhibitors(TKIs)simultaneously in China.In the present study,we aimed to estimate the cost-effectiveness of erlotinib,gefitinib,afatinib and osimertinib for untreated EGFR-mutated advanced NSCLC.A Markov model was constructed to compare the 10-year impact of four TKIs for patients with treatment-naive EGFR-mutated advanced NSCLC from the perspective of the Chinese medical system.Clinical data and utility values were derived from published literature,and costs were obtained from Chinese official websites.The primary output indicator was the incremental cost-effectiveness ratio(ICER).Sensitivity analyses were performed to test the robustness of the model.We found that afatinib was estimated to spend the lowest cost with minimum life-years(LYs),while osimertinib was the most expensive regimen with maximum LYs.The ICER of gefitinib versus afatinib was$732/quality-adjusted life-year(QALY),which was less than the willingness-to-pay(WTP)of$29382/QALY.Compared with gefitinib,erlotinib yielded a higher cost and a shorter lifetime,hence it was identified as a dominated strategy.Then,osimertinib was compared to gefitinib,which produced an ICER of$71330/QALY,exceeding the WTP.It suggested that gefitinib was the most cost-effective regimen as the first-line treatment for EGFR-mutated advanced NSCLC.Decreasing the osimertinib price or increasing the WTP threshold to$68558/QALY might enhance the favorability of the outcome,by which osimertinib might become more cost-effective.One-way sensitivity analysis manifested that the model was robust.
基金Guidance Project of Fujian Science and Technology Department(Grant No.2017Y0033)Fujian Medical Innovation Project(Grant No.2017-CX-31)+1 种基金Sail Project of Fujian Medical University(Grant No.2017XQ1068)“Weak Discipline Construction Project” of Shanghai Municipal Commission of Health and Family Planning(Grant No.2016ZB0301-01).
文摘In the present study, we aimed to develop a population pharmacokinetics(PPK) model of vancomycin(VCM) and propose the individualised dosage regimen for Chinese elderly patients. The data were collected prospectively from Chinese elderly patients receiving VCM therapy. Steady-state trough concentrations of VCM were determined using an enzyme-multiplied immunoassay. Patients’ sex, age, body weight, concomitant medications, infection type, and laboratory findings were recorded. The PPK model was developed using nonlinear mixed-effects model software. Moreover, we used Monte Carlo simulations to develop an initial dosage regimen targeting various VCM through concentration ranges based on the final model. We found that VCM clearance(CL) was significantly influenced by post-craniotomy meningitis(PCM) and glomerular filtration rate in elderly patients. Additionally, a new dosage regimen was proposed to individualise VCM regimen for PCM and non-PCM elderly patients. A PPK model was established to estimate the individual VCM CL for elderly patients, which could be applied for individualising doses in the target population.
基金Startup Fund for Scientific Research,Fujian Medical University(Grant No.2018QH1091)。
文摘Lung cancer is the most widespread type of cancer and the primary cause of cancer-related death in the world.In this study,we aimed to analyze the cost-effectiveness of second-line chemotherapy strategies based on gemcitabine,pemetrexed,and docetaxel for advanced non-squamous non-small cell lung cancer patients in China.A Markov model based on three states,progression-free survival,progressed survival and death,was constructed to simulate the progression of the disease in a 6-year horizon.Sensitivity analysis was performed to evaluate the robustness of the model.The primary outcome of the model was the incremental cost-effectiveness ratio at a willingness-to-pay threshold of 3×per capita GDP of China in 2018($29383).The baseline model results showed that the quality-adjusted life years over the course of the disease associated with second-line chemotherapy strategies were 0.233,0.417 and 0.272 for gemcitabine,pemetrexed and docetaxel,respectively,and the corresponding total costs were$5321.02,$12143.94,and$9479.42.Gemcitabine,pemetrexed and docetaxel resulted in the incremental cost-effectiveness ratios of$37081.09 and$106625.64 per quality-adjusted life year gained.The incremental cost-effectiveness ratio of pemetrexed and docetaxel compared with gemcitabine exceeded the willingness-to-pay threshold.One-way sensitivity analysis showed that the utility value of gemcitabine in the progressed survival state was the most influential parameter.
