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OBJECTIVE To evaluate the economics of serplulimab combined with chemotherapy regimens for the first-line treatment of extensive-stage small cell lung cancer （ES-SCLC） from the perspective of health system in China. METHODS A partitioned survival model was constructed based on the ASTRUM-005 clinical trial and related literature data， with a model simulation time frame of 10 years and a 3-week cycle， and both cost and utility values were discounted using a 5% discount rate. The quality-adjusted life year （QALY） was used as a model output indicator and the incremental cost-effectiveness ratio （ICER） was calculated to evaluate the economics of serplulimab combined with chemotherapy regimens （serplulimab group） versus chemotherapy alone regimens （chemotherapy alone group） for the first-line treatment of ES-SCLC. One-way sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the results of the base-case analysis and to conduct a scenario analysis for the serplulimab patient assistance program. RESULTS The results of the base-case analysis showed that compared with chemotherapy alone group， ICER of serplulimab group was 758 690.27 yuan/QALY， which was higher than 3 times China’s per capita gross domestic product （GDP） in 2022 as the willingness-to-pay （WTP） threshold. The results of the scenario analysis showed that compared with chemotherapy alone group， the ICER of serplulimab group was 172 275.74 yuan/QALY， which was below above WTP threshold. The one-way sensitivity analysis showed that the progress-free survival utility value， serplulimab price and so on had a significant impact on the model results. The results of the probabilistic sensitivity analysis showed that the probability of the serplulimab group being economic was 0 when the serplulimab patient assistance program was not considered， but 100% when the patient assistance program was considered. CONCLUSIONS At a WTP threshold of 3 times China’s per capita GDP in 2022， the serplulimab group is no cost-effectiveness compared to the chemotherapy alone group； however， this result is reversed when the patient assistance program is taken into account.
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OBJECTIVE To evaluate the cost-effectiveness of denosumab and zoledronic acid in the treatment of postmenopausal osteoporosis ，and to provide reference for relevant decision-making. METHODS From the perspective of Chinese health system ，Excel 2003 software was used to establish Markov model ，and cost-utility analysis was used to evaluate the cost-effectiveness of denosumab or zoledronic acid combined with calcium carbonate D 3 in the treatment of postmenopausal osteoporosis. Pharmacotherapy effects were obtained from the network Meta-analysis ，and cost and health-utility value data were obtained from the published literature or network ，etc. The model cycle was 1 year，and the simulation time limit was the patient ’s lifetime. One-way sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the impact of model parameter changes on the robustness of the results ；and the cost-effectiveness of changing the medication cycle of zoledronic acid were explored through scenario analysis. RESULTS Denosumab regimen was more effective than zoledronic acid regimen （12.77 QALYs vs. 11.98 QALYs），and its cost was also higher than zoledronic acid regimen （51 224.56 yuan vs. 49 221.67 yuan）， and the incremental cost-effectiveness ratio was 2 544.14 yuan/QALY. One-way sensitivity analysis showed that the cost of Zoledronic acid injection and that of Denosumab injection had great impact on the results. The results of probabilistic sensitivity analysis showed that when using 3 times of per capita gross domestic product （GDP）in China in 2021 as the threshold of willingness to pay ，the probability of Denosumab regimen being cost-effective was 85.4％. The results of the scenario analysis showed that the Denosumab regimen was still more cost-effective when the dosing cycle of zoledronic acid was changed. CONCLUSIONS Under the threshold of 1-3 times of Chinese per capita GDP in 2021，denosumab combined with calcium carbonate D 3 is more cost-effective than zoledronic acid combined with calcium carbonate D 3 in the treatment of postmenopausal osteoporosis.
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OBJECTIVE To evaluate the cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer from the perspective of the Chinese health care system. METHODS A Markov model was developed by using updated four-year survival data from the PACIFIC trial in May 2021 and relevant literature. The cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer was evaluated by using quality-adjusted life years （QALYs）as health output index with 20-year simulation time frame and a 2-week cycling period. The costs and health output were discounted using discount rate of 5％；one-way sensitivity analysis and probabilistic sensitivity analysis were used to examine the robustness of the model simulation results. RESULTS The results of the base analysis showed that compared with placebo group ，durvalumab resulted in 0.73 QALYs at an incremental cost of 1 076 062.86 yuan and an incremental cost-utility ratio （ICER）of 1 467 546.54 yuan/QALY，which was much higher than 3-fold per capita gross domestic products （GDP）in 2020（217 713 yuan）as willingness-to-pay （WTP）threshold. The results of one-way sensitivity analysis showed that the price of durvalumab and discount rate had a great impact on ICER. Probabilistic sensitivity analysis showed no cost-effective advantage for durvalumab when the WTP threshold was three times of GDP per capita in 2020 （217 713 yuan）. CONCLUSIONS From the perspective of Chinese health care system ，there is no cost-effective advantage to the use of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer when the WTP threshold was three times of GDP per capita in 2020.
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OBJECTIVE To evaluate the cost-utility of pembrolizumab combined with chemotherapy versus chemotherapy alone in the first-line treatment of advanced or metastatic esophageal carcinoma. METHODS Cost-utility analysis of pembrolizumab combined with chemotherapy versus chemotherapy alone for advanced or metastatic esophageal carcinoma was conducted by using a three-state partitioned survival model from the perspective of health system in China. The model use d a lifetime simulation time frame with 3 weeks as a cycle. The survival data were extrapolated using KEYNOTE- 590 data；cost data were obtained from the median of 2022 public winning bid on Yaozhi network ，among which the price of pembrolizumab was obtained after discounting by a patient assistance program ；utility data were obtained from the literatures ，and a 5％ discount rate was used for both cost and utility. One-way sensitivity analysis and probabilistic sensitivity analysis were also conducted to examine model robustness. RESULTS Analysis of the base case results showed that compared to chemotherapy alone ，the incremental cost-effectiveness ratio （ICER）of pembrolizumab combined with chemotherapy regimens were 950 528.42 yuan/QALY，107 845.39 yuan/QALY and 315 754.56 yuan/QALY for esophageal squamous cell carcinoma （ESCC），programmed deathligand- 1 combined positive score （PD-L1 CPS）≥10 and intention-to-treat population （ITT），respectively. The results of sensitivity analysis verified the robustness of the basic analysis results. CONCLUSIONS Under our healthcare system ，using a threshold of willingness-to-pay of 1-3 times our GDP per capita in 2021，pembrolizumab combined with chemotherapy regimen isn ’t cost-utility compared with chemotherapy alone in the ESCC and ITT subgroups of patients ，while it is cost-utility in the PD-L 1 CPS≥10 subgroup of patients.
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OBJECTIVE To systematically evaluate the economical efficiency of marketed a naplastic lymphoma kinase （ALK）-tyrosine kinase inhibitors （TKI）for the treatment of ALK-positive non-small cell lung cancer （NSCLC）in China ，and to provide a reference for the selection of China ’s medical insurance list and drug pricing. METHODS Computer searches of databases such as CNKI ，Wanfang database ，VIP，PubMed，Embase and the Cochrane Library were conducted to collect pharmacoeconomic evaluation studies of four marketed ALK-TKI （crizotinib，seretinib，aletinib and ensatinib ）in the treatment of ALK-positive NSCLC in China during the inception to July 2021. The qualities of the included literature were evaluated using CHEERS checklist ，and analyzed systematically in terms of both methodological and economic outcomes. RESULTS A total of 6 literatures were included ，with a compliance rate of 71％ to 83％ for the CHEERS list criteria ，and the overall quality of the literature was high. In terms of methodological analysis ，the pharmacoeconomic evaluation methods included in the study were mainly model-based （Markov or partitioned survival models ） and real-world data-based cost-utility analysis. Most research perspectives were health insurance payer and health system perspectives ；all cost types were direct medical costs. In terms of economical efficiency analysis ，compared with chemotherapy plan ，2 studies confirmed that ALK-TKI （crizotinib，seretinib）were not economic ，1 study confirmed ALK-TKI （crizotinib） showed economical efficiency. Seretinib showed relatively higher economical efficiency when compared to other ALK-TKIs. High drug prices were the main factor why ALK-TKI was not economically viable for treating ALK-positive NSCLC. CONCLUSIONS The second-generation ALK-TKI （seretinib， 163.com alectinib） have better economical efficiency than the first-generation ALK-TKI （crizotinib）. The economical efficiency of seretinib is the best among the second-generation · ALK-TKI. The economical efficiency of chemotherapy regimen is better than that of the second-generation ALK-TKI （seretinib）. Economic comparison between chemotherapy and first-generation ALK-TKI （crizotinib）remains controversial.
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Objective@#To study the effect and mechanism of angiotensin (Ang II) on the proliferation of human hepatocellular carcinoma HepG2 cells.@*Methods@#The effects of different concentrations of Ang II's (10-8-10-4 mol/L) on proliferated hepatocellular carcinoma HepG2 cells were detected by CCK-8 assay. The expression of angiotensin II type 1 receptor (AT1) protein and activation of ERK1/2 protein in hepatocellular carcinoma HepG2 cells after processing with Ang II were assayed by Western blot. The cells were pretreated with candesartan (AT1 receptor antagonist), sorafenib (Raf kinase inhibitor) and PD98059 (ERK1/2 inhibitor) for 1.5 h and then Ang II (10-6 mol/L) was added. CCK-8 assay was used to determine whether it could reverse the proliferation of Ang II, and ERK phosphorylation levels were detected by Western blot. The changes in Bcl-2 and c-myc gene expression before and after Ang II processing were detected by Rt-PCR. According to different data, t-test, one-way analysis of variance or SNK method were used for statistical analysis.@*Results@#HepG2 cells treated with different concentrations of Ang II promoted cell proliferation after 24h and 48h. After 24 h, cell vitality was strongest with Ang II concentration 10-5 mol/L and the absorbance value was 0.990 8±0.097 8; and again after 48 h, the cell viability was strongest with Ang II concentration 10-6 mol/L and the absorbance value was 1.302 7 ± 0.030 9. Moreover, the pro-proliferation effect of Ang II on HepG2 cells blocked candesartan, sorafenib and ERK1/2 isolated inhibitors. After treatment with 10-6 mol/L Ang II, Western blot showed that Ang II significantly promoted AT1 receptor expression and phosphorylation of ERK1/2 protein confirmed that Ang II activated the AT1/RAF/ERK1/2 signaling pathway. In addition, Rt-PCR detection showed that the downstream of Bcl-2 and c-myc genes expressions rose significantly when the concentration of Ang II ranged from 10-8 to 10-6 mol/L.@*Conclusion@#Ang II can promote the proliferation of HepG2 cells by activating AT1/Raf /ERK1/2 signaling pathway and enhance the downstream of Bcl-2 and c-myc gene expression.
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Objective To survey on training for general practice backbone mentors in tertiary hospitals of Hebei province.Methods A questionnaire survey on training status was conducted among general practice backbone mentors in tertiary hospitals of Hebei Province.The survey items included the basic information,knowledge of general practice and its training,suggestions for mentors training and general practice discipline construction in tertiary hospitals.Results Total 208 questionnaires were distributed and 208 were retrieved with a recovery rate of 100％.Among 208 participants,all of them were over the age of 30;202 (97.1％) had bachelor degree or above;202 (97.1％) were attending doctors or above;165 (79.3％) had worked for more than 10 years;169 (81.3％) had no or little knowledge of general practice;159 (76.4％)had not received general practice training before;124 (59.6％) thought that general practitioners were not qualified as "gatekeeper" at present;and 192 (92.3％) worked in the hospitals providing standardized residency training.The training contents in general section were prioritized as clinical skills,community health service development and policy,rules for general practice standardized training,theoretical training,the present situation and countermeasure of general teaching,the doctor-patient relationship and medical ethics.The contents in training method section were prioritized as lecture series of clinical medicine,case discussion,seminar,distance education with classroom teaching.The suggestions for mentors training included:the exploration of standardized training model,perfecting continuing education system for general practice mentors,more attention to the training at community health service centers and the consummation of general practice system.The suggestions for general practice discipline construction were that more attentions should be paid by the government and the hospitals leaders,the general practice departments in tertiary hospitals should closely cooperate with community health service centers in training ofqualified general practitioners.Conclusions The specialists in tertiary hospitals of Hebei province do not have enough knowledge about general practice and do not quite understand the necessity of establishment of general practice department,so the training for general practice mentors should be strengthened and improved.Properly policy and more social resources from the government and the hospitals leaders will be helpful for construction of general practice discipline in general hospital.
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Objective To investigate the distribution and characteristics of drug resistance of pathogens in premature infants with ventilator‐associated pneumonia(VAP) ,and explore the therapeutic measures for premature infants with VAP ,so as to provide references for clinically reasonable administration of antibacterial agents .Methods A total of 54 cases of premature infants diag‐nosed with VAP in the First Affiliated Hospital of Xiamen University from January 2013 to June 2014 were enrolled in this study . Specimens of respiratory tract secretion were collected ,and species identification of pathogens and drug sensitivity test were per‐formed by VITEK 2 Compact system .Results A total of 69 strains were isolated .Gram negative bacteria was accounted for 94 .20% ,and gram positive bacteria was accounted for 5 .80% .Four of the most common pathogenic bacteria were Klebsiella pneu‐monia (29 strains ,42 .03% ) ,Enterobacter aerogenes (12 strains ,17 .39% ) ,Pseudomonas aeruginosa (10 strains ,14 .49% ) and Stenotrophomonas maltophilia(7 strains ,10 .14% ) .The results of antibiotics‐sensitivity tests showed that these strains were multi‐drug resistant to most commonly used antibiotics ,but sensitive to only a few antibiotics .Conclusion Gram‐negative bacteria are the major pathogens for premature infants with VAP in this hospital .Mixed infection and multidrug resistance are common .Therefore , the rational use of antibiotics according to drug sensitivity tests′results is critical in treating VAP .
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Objective To investigate the preventive effect of intrarectal application of indomethacin on hyperamylasemia and acute pancreatitis after endoscopic retrograde cholangiopancreatography ( ERCP ) .Methods 180 patients who underwent ERCP were randomly divided into the indomethacin group, somatostatin group and control group.The serum amylase levels were measured before ERCP, 3 and 24 hours after the drug application.The incidences of post-ERCP hyperamylasemia and pancreatitis were observed.Results Serum amylase levels before and 3h after ERCP of three groups had no differences.The serm amylase levels of control group 24 h after ERCP (228.50 ±121.72) U/L was significantly higher than that of indomethacin group (94.09 ±68.45) U/L (P <0.01) and somatostatin group (76.53 ±74.47) U/L (P <0.05), while there was no difference between indomethacin group and somatostatin group.Compared with before ERCP, the serum amylase levels significantly increased in both control group 3 and 24h after ERCP (P <0.01), as well as in both indomethacin group and somatostatin group 3h after ERCP (P <0.05), but there were no apparent differences between pre-ERCP and 24 h after ERCP in both indomethacin group and somatostatin group.The incidences of post-ERCP hyperamylasemia in both indomethacin group and somatostatin group ( 10.00%, 11.67%) respectively was much lower than that in control groups (35.00%, P<0.01).The incidence of post-ERCP pancreatitis in indomethacin group (3.33%) was also lower than that in control group (15.00%, P<0.05), whlie there was no difference between indomethacin group and somatostatin group (5.00%).Conclusion The intrarectal application of indomethacin can effectively prevent acute pancreatitis after ERCP, which has the same effect as intravenous application of somatostatin.It is also convenient, economic and safe.
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To investigate the effects of 2-(4-methoxycarbonyl-2-tetradecyloxyphenyl)carbamoylbenzoic acid (CX09040) on protecting pancreatic β cells, the β cell dysfunction model mice were induced by injection of alloxan into the caudal vein of ICR mice, and were treated with compound CX09040. Liraglutide was used as the positive control drug. The amount and the size of islets observed in pathological sections were calculated to evaluate the β cell mass; the glucose stimulated insulin secretion (GSIS) test was applied to estimate the β cell secretary function; the oral glucose tolerance test (OGTT) was taken to observe the glucose metabolism in mice; the expressions of protein in pancreas were detected by Western blotting. The effects on the target protein tyrosine phosphatase 1B (PTP1B) were assessed by the PTP1B activities of both recombinant protein and the intracellular enzyme, and by the PTP1B expression in the pancreas of mice, separately. As the results, with the treatment of CX09040 in alloxan-induced β cell dysfunction mice, the islet amount (P<0.05) and size (P<0.05) increased significantly, the changes of serum insulin in GSIS (P<0.01) and the values of acute insulin response (AIR, P<0.01) were enhanced, compared to those in model group; the impaired glucose tolerance was also ameliorated by CX09040 with the decrease of the values of area under curve (AUC, P<0.01). The activation of the signaling pathways related to β cell proliferation was enhanced by increasing the levels of p-Akt/Akt (P<0.01), p-FoxO1/FoxOl (P<0.001) and PDX-1 (P<0.01). The effects of CX09040 on PTP1B were observed by inhibiting the recombinant hPTP1B activity with IC50 value of 2.78x 10(-7) mol.L-1, reducing the intracellular PTP1B activity of 72.8% (P<0.001), suppressing the PTP1B expression (P<0.001) and up-regulating p-IRβ/IRβ (P<0.01) in pancreas of the β cell dysfunction mice, separately. In conclusion, compound CX09040 showed significant protection effects against the dysfunction of β cell of mice by enlarging the pancreatic β cell mass and increasing the glucose-induced insulin secretion; its major mechanism may be the inhibition on target PTP1B and the succedent up-regulation of β cell proliferation.
Subject(s)
Animals , Mice , Alloxan , Benzoates , Pharmacology , Biological Assay , Disease Models, Animal , Glucose , Metabolism , Glucose Tolerance Test , Insulin , Bodily Secretions , Insulin Resistance , Insulin-Secreting Cells , Liraglutide , Pharmacology , Mice, Inbred ICR , Molecular Weight , Pancreas , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Signal TransductionABSTRACT
Diabetes patients tend to have the gastrointestinal motility disorder. Although the relationship between the motility disorder and both the neurons and Cajal cells in the enteric nervous system (ENS) is well established, little is known about the role of enteric glial cells (EGCs) in gastric motility in diabetes. This study aimed to examine the expression of the glial marker S100B and morphology of EGCs in gastric tissues and the relationship between activated EGCs and the damage of gastric emptying in diabetic models. The diabetic model of rat was induced with 1% streptozotocin (STZ). The model rats at 7-14 days and at 56-63 days were defined as early diabetic rats and advanced diabetic rats, respectively, and normal rats at the two time periods served as their corresponding controls. The gastric emptying rate of the rats was tested by using the phenol red solution. The ultrastructure of EGCs in the gastric antrum was observed by the transmission electron microscopy, and the expression of S100B in the myenteric plexus was immunohistochemically detected. The results showed that the gastric emptying rate was significantly increased in the early diabetic rats and decreased in the advanced diabetic rats when compared with their corresponding control rats (P<0.01 for both). The ultrastructure of EGCs was mostly normal in both the early diabetic and control groups. Vacuolization of mitochondria and expansion of endoplasmic reticulum occurred in both the advanced diabetic group and its control group, and even the structure of smooth muscle cells and intestinal neurons was destroyed in the advanced diabetic group. The expression level of S100B in the advanced diabetic group was significantly decreased compared with its control group (P<0.05). It was obviously increased in the early diabetic control group when compared with the advanced diabetic control group (P<0.05). However, there was no significant difference in the S100B expression between the early diabetic group and its control group (P>0.05). The findings suggested that the gastric motility dysfunction in diabetes may be associated with the changes of morphology and number of EGCs in the myenteric plexus.
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Animals , Male , Rats , Diabetes Mellitus, Experimental , Pathology , Gastrointestinal Motility , Physiology , Neuroglia , Pathology , Rats, Sprague-DawleyABSTRACT
Diabetes patients tend to have the gastrointestinal motility disorder. Although the relationship between the motility disorder and both the neurons and Cajal cells in the enteric nervous system (ENS) is well established, little is known about the role of enteric glial cells (EGCs) in gastric motility in diabetes. This study aimed to examine the expression of the glial marker S100B and morphology of EGCs in gastric tissues and the relationship between activated EGCs and the damage of gastric emptying in diabetic models. The diabetic model of rat was induced with 1% streptozotocin (STZ). The model rats at 7-14 days and at 56-63 days were defined as early diabetic rats and advanced diabetic rats, respectively, and normal rats at the two time periods served as their corresponding controls. The gastric emptying rate of the rats was tested by using the phenol red solution. The ultrastructure of EGCs in the gastric antrum was observed by the transmission electron microscopy, and the expression of S100B in the myenteric plexus was immunohistochemically detected. The results showed that the gastric emptying rate was significantly increased in the early diabetic rats and decreased in the advanced diabetic rats when compared with their corresponding control rats (P0.05). The findings suggested that the gastric motility dysfunction in diabetes may be associated with the changes of morphology and number of EGCs in the myenteric plexus.