Cost-effectiveness of mepolizumab for severe eosinophilic asthma in China.

OBJECTIVE: To evaluate the economic value of mepolizumab as an add-on therapy to the standard of care (SoC) for patients with severe eosinophilic asthma in China. METHODS: A Markov model with three health conditions was constructed to calculate the incremental cost per quality-adjusted life year (QALY) in mepolizumab with SoC and SoC only groups from the perspective of the Chinese healthcare system throughout an entire lifespan. The model was populated with local costs, while efficacy parameters were obtained from the global Phase III MENSA trial and mortality was derived from two surveys. One-way and probabilistic sensitivity analyses were conducted. Additional scenario analysis was used to estimate the cost-effectiveness impact of changes in the price of mepolizumab. RESULTS: Over the lifetime treatment horizon, the incremental cost-effectiveness ratio (ICER) of mepolizumab plus SoC compared to SoC alone was $170 648.73 per QALY. Sensitivity analyses focused on these results. Scenario analysis showed that mepolizumab would require a price reduction of at least 82% to reach the current willingness-to-pay (WTP=$38 223.34/QALY) threshold. CONCLUSION: Mepolizumab is not a cost-effective healthcare resource in China at its current pricing.

Pharmacoeconomic evaluation of omalizumab in the treatment of severe allergic asthma / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of omalizumab in the treatment of severe allergic asthma from the perspective of healthcare providers in China. METHODS Based on the data from an international multicenter study of omalizumab in the treatment of severe allergic asthma， the Markov model was constructed according to the progression of severe allergic asthma， with a cycle of 4 weeks. Long-term health outcomes and costs of omalizumab combined with standard of care（SoC） regimen versus SoC regimen in the treatment of severe allergic asthma were simulated by using quality-adjusted life years （QALYs） and incremental cost-effectiveness ratio（ICER） as output indexes. One-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis were performed to test the robustness of the results. RESULTS Compared with the SoC regimen， ICER for the omalizumab combined with SoC regimen was 107 723.05 yuan/QALY， which was less than the willingness-to-pay（WTP） threshold （268 074 yuan/QALY） calculated by three times per capita gross domestic product（GDP） in China in 2023. The one-way sensitivity analysis showed that the baseline serum level of immunoglobulin E had the greatest impact on the robustness of the model. The probabilistic sensitivity analysis showed that the omalizumab+SoC regimen had a 93.00% probability of being cost- effective. The scenario analysis showed that in the real world， the billing method of omalizumab based on specifications rather than actual usage may increase ICER. CONCLUSIONS Compared with the SoC regimen， the combination of omalizumab and SoC regimen for treating severe allergic asthma is cost-effective， with a WTP threshold of three times China’s per capita GDP

Cost calculation of centralized dispensing of 4 categories of drugs in pharmacy intravenous admixture service / 中国药房

OBJECTIVE To calculate the cost of centralized dispensing of four categories of drugs （ordinary drugs， antibacterial drugs， hazardous drugs， and parenteral nutrition solutions） in pharmacy intravenous admixture service （PIVAS）， and provide reference for setting charging standards for relevant departments. METHODS The operating costs of PIVAS in 12 medical institutions from Shaanxi province were collected through questionnaire survey， including labor costs， medical and health material costs， fixed asset depreciation and repair costs， water and electricity costs， and management costs. The operation time allocation coefficient method and workload allocation coefficient method were comprehensively used to allocate the above costs， and the unit preparation costs of four categories of drugs were calculated. RESULTS The average annual total costs of dispensing ordinary drugs， antibacterial drugs， hazardous drugs， and parenteral nutrition solutions in Shaanxi province were （2 195 900.25±1 680 893.73） yuan， （746 341.59±725 839.39） yuan， （331 420.15±183 258.83） yuan， and （330 322.68±277 281.70） yuan， respectively， with labor costs accounting for the highest proportion， averaging 85.49%. The costs of dispensing a set of ordinary drugs， antibacterial drugs， and hazardous drugs were 5.89， 7.60， and 14.37 yuan， respectively； the cost of dispensing one bag of parenteral nutrition solution was 32.15 yuan （excluding the cost of disposable intravenous nutrition bags）. CONCLUSIONS The cost calculation method and data of different types of intravenous drugs obtained in this study can provide reference for relevant departments to formulate and adjust PIVAS fee standards.

Cost calculation of centralized dispensing of 4 categories of drugs in pharmacy intravenous admixture service / 中国药房

OBJECTIVE To calculate the cost of centralized dispensing of four categories of drugs （ordinary drugs， antibacterial drugs， hazardous drugs， and parenteral nutrition solutions） in pharmacy intravenous admixture service （PIVAS）， and provide reference for setting charging standards for relevant departments. METHODS The operating costs of PIVAS in 12 medical institutions from Shaanxi province were collected through questionnaire survey， including labor costs， medical and health material costs， fixed asset depreciation and repair costs， water and electricity costs， and management costs. The operation time allocation coefficient method and workload allocation coefficient method were comprehensively used to allocate the above costs， and the unit preparation costs of four categories of drugs were calculated. RESULTS The average annual total costs of dispensing ordinary drugs， antibacterial drugs， hazardous drugs， and parenteral nutrition solutions in Shaanxi province were （2 195 900.25±1 680 893.73） yuan， （746 341.59±725 839.39） yuan， （331 420.15±183 258.83） yuan， and （330 322.68±277 281.70） yuan， respectively， with labor costs accounting for the highest proportion， averaging 85.49%. The costs of dispensing a set of ordinary drugs， antibacterial drugs， and hazardous drugs were 5.89， 7.60， and 14.37 yuan， respectively； the cost of dispensing one bag of parenteral nutrition solution was 32.15 yuan （excluding the cost of disposable intravenous nutrition bags）. CONCLUSIONS The cost calculation method and data of different types of intravenous drugs obtained in this study can provide reference for relevant departments to formulate and adjust PIVAS fee standards.

Research progress on pharmacokinetics and toxicity of vinorelbine / 中国药房

Vinorelbine（NVB）is a semisynthetic vinca alkaloid and can play an anti-tumor role by inhibiting the synthesis of tubulin. Its oral preparation has been used in the treatment of a variety of tumors as its convenience and good clinical response. The blood concentration of NVB is closely related to its curative effect and toxicity. Small variations in blood concentration may reduce the curative effect and even produce serious toxicity. There are some risks in the clinical drug use due to limited clinical data and effective pharmacodynamic monitoring methods. By reviewing the relevant literature at home and abroad ，this paper summarizes the research progress of in vivo pharmacokinetics and toxicity of NVB ，fully understands the pharmacokinetic characteristics and influencing factors of NVB ，the influencing factors of toxicity ，and the application status of pharmacokinetics in the adjustment of administration scheme ，so as to provide reference for its clinical rational use.

Pharmacoeconomic Evaluation of Dapagliflozin Combined with Metformin in the Treatment of Type 2 Diabetes Mellitus / 中国药房

OBJECTIVE：To evaluate the economic value of dapagliflozin combined with metformin in the treatment of type 2 diabetes mellitus （T2DM）. METHODS ：Based on related literatures and phase 3 randomized controlled clinical trial （RCT）of metformin alone or combined with dapagliflozin for T2DM，Markov model was built to simulate the dynamic changes of 3 schemes such as 5 mg dapagliflozin combined with metformin ，10 mg dapagliflozin combined with metformin or metformin alone （the dose of metformin were all 1 500 mg）in the treatment of T 2DM patients without or with complications and death . Quality adjusted life years（QALYs）was used as a health output indicator and the threshold of willingness-to-pay was 3 times of GDP in 2019. Cohort simulation in Markov model was applied to obtain long-term effect and cost of 3 schemes in the treatment of T 2DM. The incremental cost-effectiveness ratio （ICER）was analyzed ；the sensitivity of cost ，utility and discount was analyzed to check the stability of the analysis result. RESULTS ：According to the results of Markov model cohort simulation ，after 10 years of disease progression，compared with metformin alone ，ICER of 5 mg dapagliflozin combined with metformin was 41 259.17 yuan/QALYs， and that of 10 mg dapagliflozin combined with metformin was 92 824.85 yuan/QALYs. Compared with 5 mg dapagliflozin combined with metformin ，ICER of 10 mg dapagliflozin combined with metformin was 1 209 525.95 yuan/QALYs. Extension of termination time to 20 or 30 years had no effect on results. According to the sensitivity analysis ，the change of key parameters in the set range did not affect the model results ，indicating the result was stable. CONCLUSIONS ：For T 2DM，5 mg dapagliflozin combined with metformin is more cost-effective .

Investigation and Study on Occupational Exposure for Hazardous Drugs of Healthcare Workers in Shaanxi Province and Relative Cognition Level / 中国药房

OBJECTIVE：To understand the situation of healthcar e workers’occupational exposure of hazardous drugs （chemotherapeutic drugs and antiviral drug ）and relative cognition level ，and to provide reference for improving the level of occupational protection. METHODS ：During Oct. 2018 to Mar. 2019，healthcare workers from 12 hospitals of different levels and different departments in Shaanxi province were selected as respondents to conduct a self-designed questionnaire survey. Information we surveyed contained baseline characteristics ，hazardous drugs exposure ，physical health status ，and occupational protection. Valid questionnaires were collected and analyzed statistically. RESULTS ：A totally of 1 848 questionnaires were sent out ，and 1 767 questionnaires were collected ，including 95 were pharmacists ，100 were physicians ，and 1 572 were nurses. The frequency of diarrhea and menstrual disorders in healthcare workers with long-term exposure to antiviral drugs （antiviral drug exposure group ） and cross-exposure to antiviral drugs and chemotherapeutic drugs （cross-exposure group ）were significantly higher than unexposed group （P＜0.05）. The incidence of routine blood abnormalities in cross-exposure group ，antiviral drug exposure group and healthcare workers with long-term exposure to chemotherapy drugs （chemotherapy drug exposure group ） was higher than unexposed group by 9.13％，5.50％ and 12.34％，respectively. 84.7％ of the respondents had little knowledge of hazardous drugs ， and 8.15％ of the respondents had never received occupational protection training. Additionally ，the ratio of healthcare workers receiving occupational protection training in the cross-exposure group was significantly higher than unexposed group （P＜0.05）， and the ratio of healthcare workers receiving occupational protection training in antiviral drug exposure group were significantly lower than unexposed group （P＜0.05）. CONCLUSIONS ：Long-term exposure to hazardous drugs will cause certain occupational hazards to healthcare workers. It is necessary to improve healthcare workers ’awareness of self-protection ，increase the input of hospitals in occupational protection training and establish occupational protection standards in order to improve the current situation of occupational protection of healthcare workers.

Clinical Distribution and Drug Resistance of Enterococcus in Our Hospital from Jan. 2009 to Jun. 2017 / 中国药房

OBJECTIVE:To provide reference for hospital infection treatment and control. METHODS:The etiological data of Enterococcus isolated from clinical specimens were collected from our hospital during Jan. 2009-Jun. 2017. The drug resistance of commonly used antibiotics and infection related risk factors were analyzed retrospectively. RESULTS:A total of 6252 isolates of Enterococcus were isolated,of which there were 1994 strains of E. faecalis and 3575 strains of E. faecium. The bacteria were mainly isolated from urine(2009 strains),drainage liquids(1538 strains),bile(1168 strains),wound secretions(561 strains), blood (493 strains). The detection rate increased 9.4％ in 2009 to 13.4％ in 2017. Resistance rate of E. faecalis to ampicillin, penicillin and vancomycin showed a wavelike decrease,and E. faecalis showed low resistance rate to vancomycin,teicoplanin, linezolid and tigecycline. Resistance rate of E. faecalis to ciprofloxacin,moxifloxacin and levofloxacin decreased wavily to 2014 but showed a fluctuating upward trend since 2015. Resistance rate of E. faecium to linezolid decreased from 1.9％ in 2009 to 0.2％ in Jun. 2017;resistance rate of E. faecium to vancomycin and teicoplanin continues to fluctuate,but it is still at a low level;resistance rate of E. faecium to tetracycline decreased, but that to high concentration gentamicin increased. There were 43 strains of vancomycin-resistant E. faecium and 8 trains of vancomycin-resistant E. faecalis detected in 51 patients. Resistant rates of vancomycin-resistant E. faecium to linezolid,tigecycline and teicoplanin were 23.3％,0,35.3％,respectively. Resistant rates of vancomycin-resistant E. faecalis to linezolid,tigecycline and teicoplanin were 0. Pearson relationship analysis showed that days in ICU (r=0.225,P<0.01),tracheotomy or intubation (r=0.314,P<0.01),days of antibiotic use (r=0.347,P<0.01),types of antibacterial drugs (r=0.226,P<0.01),use of glucocorticoids (r=0.190,P<0.01),and days of carbapenems use (r=0.173,P<0.05)were positively correlated with vancomycin-resistant E. faecium infection rate and vancomycin-resistant E. faecalis infection rate. CONCLUSIONS:The detection rate of Enterococcus in our hospital is fluctuating upward. E. faecalis and E. faecium were the main types,mainly from urine and drainage fluids. The resistance rate of Enterococcus most of antibiotics shows a downward trend. The resistance rate of E. faecium to high concentration gentamycin is on the rise,while that of E. faecium to linezolid and tetracycline is decreased. The appropriate antibiotics should be selected according to the patient's condition and drug susceptibility results.

Discussion on the Common Ethical Issues in Clinical Pharmacy / 中国医学伦理学

This paper summarized the common medical ethical issues in clinical pharmacy service and analyzed them from the perspective of medical ethics.It put forward some countermeasures to solve these problems,such as helping clinical pharmacists to establish a patient-centered service mode,improving their occupation accomplish-ment,and avoiding moral issues and medical disputes caused by ethical issues under the premise of ensuring pa-tients' safety and rational use of drugs,and thus to comprehensively improve service level of clinical pharmacists.

Risk Factors Study for Lung Cancer Patients with Chemotherapy-induced Severe Neutropenia / 中国药师

Objective:To discuss the risk factors in lung cancer patients with chemotherapy-induced severe neutropenia to provide reference for clinical drug use. Methods:A retrospective analysis was performed for the patients with lung cancer,and the risk factors of severe neutropenia were statistically analyzed and found out. Results:The results of single factor experiments showed that the incidence of severe neutropenia was related with radiotherapy history,cycles of chemotherapy and the use time of granulocyte colony factor. Based on a binary logistic regression analysis,the history of radiotherapy and the use of granulocyte colony factor were the significant risk factors of severe neutropenia in the lung cancer patients. Conclusion:For the patients with radiotherapy history,it is better to choose chemotherapy drugs with lower toxicity,decrease drug dosage or preventively use granulocyte colony factor. The rational use of rhG-CSF can alleviate chemotherapy-induced severe neutropenia.

Ambiguity and Countermeasures in the Drug Instruction Manual / 中国药房

OBJECTIVE:To provide reference for clinical use and revision of drug instruction manual. METHODS:The ambi-guity in drug instructions manual was summarized and countermeasures of revision were presented based on the practical clinical conditions. RESULTS & CONCLUSIONS:The problems of drug instruction manual that may mislead the patients and medical per-sonnel were as follows as controversial main contents,unclear descriptions of instruction,unfocused contents or without key points,one instruction for multiple drugs,obvious or inaccurate translations,words without popularity and standardization and wrong sentence division or non-standard typesetting. It is suggested that the manufacturers should attach highly importance to the re-vision of drug instruction manual;the revisers should understand the meaning of drugs instruction manual and know the subjects;the premarketing instructions should be tested and investigated by necessary persons;the major and cultural quality of revisers should be improved;the approval monitoring should be strengthened and the feedback mechanism should be established to further improve the instructions,guide the medical staff and patients with accurate use of drugs and ensure the safe drug use of patients.

Analysis of Irrational Prescriptions and Pharmacists’Intervention in the Pharmacy Intravenous Admixture Service of Our Hospital / 中国药房

OBJECTIVE:To provide some references for rational application of intravenous infusion drugs to ensure the safety of drug use. METHODS:Statistical analysis was made to irrational prescriptions intercepted by the pharmacy intravenous admixture service of our hospital from 2009 to 2013. RESULTS:There were 5,802 groups of irrational prescriptions from 2009 to 2013,accounting for 0.12% of total prescriptions. For the irrationality,the top three reasons were improper solvent dosage, drug overdose and improper solvent selection in order,and the involved types of drugs were mainly antimicrobial agents,anti-neoplastic drugs,common drugs and parenteral nutrition drugs (arranged from more to less). Under the pharmacist’s interven-tion,the percentage of irrational prescriptions of intravenous drugs reduced from 0.169 4% in 2009 to 0.082 8% in 2013. The decrease in the irrational prescriptions involving with improper administration was the most significant,followed by those related to drug overdose,frequency,prescribing errors errors improper solvent dosage,incompatibility and improper solvent. CONCLU-SIONS:Pharmacists’intervention can effectively reduce the irrational prescriptions and significantly promote rational use of in-travenous drugs.

Medication Analysis for One Patient with Severe Ulcerative Colitis / 中国药师

Objective:To analyze the medication of one patient with ulcerative colitis to provide pharmaceutical care and support for rational drug use in patients with ulcerative colitis. Methods:During the treatment of the patient with severe ulcerative colitis, clin-ical pharmacists analyzed the drugs used by the patient and provided pharmaceutical care for doctors and the patient according to the ex-amination and diagnosis of the patient. Results:The compliance, therapeutic effect and medication safety of the patient were all im-proved by giving clinical drug rationalization suggestions and targeted medication monitoring and education, which fully embodied the necessity of work of clinical pharmacists in the medication of patients. Conclusion:Through case analysis, clinical thinking of clinical pharmacists can be developed to promote rational drug use, avoid adverse drug reactions and achieve optimal effect of drug treatment.

Effect of methylcobalamin,gliclazide and combined application of both on sciatic nerve morphology and nerve growth factor contents in streptozotocin-induced diabetic rats / 中国药理学通报

Aim To investigate the curative effect and the mechanism of methylcobalamin,gliclazide and combined application of both on diabetic peripheral neuropathy(DPN)in streptozotocin-induced diabetic(STZ-D)rats.Methods STZ-D rats were administered with drugs orally for 8 weeks after streptozotocin treatment.Morphologies of sciatic nerve were observed with histological method.Nerve growth factor(NGF)contents in plasma or in sciatic nerve tissues were determined by ELISA kit or immunohistochemistry.Results Morphological degeneration in sciatic nerve,decrease of NGF concertration in plasma,as well as in nerve axis cylinder,in diabetic rats was all ameliorated by methylcobalamin and/or gliclazide.However,no significant differences in morphology and NGF contents were found between single drug treated groups and combined application group.Conclusions The observations suggest that methylcobalamin,gliclazide and combined application are effective in treating DPN in STZ-D rats.No significantly enhanced effect is found in combined application group as compared with methylcobalamin or gliclazide group.

Experimental study on treatment of epigastralgia with Shugan Pills / 中成药

AIM: To study the action of Shugan Pills (SHGP) (Fructus Toosendan, Rhizoma corydalis, Radix Paloniae Albe, Radix Aucklandiae, Cortex Magnoliae Officinalis, Fructus Aurantii, etc.) on treatment of epigastralgia. METHODS: The analgesic effect was tested by the hot plate test and writhing method. The anti gastric ulcer action of SHGP was observed on the gastric ulcer induced by water immersion stress, reserpine and absolute ethyl alcohol. The effect on gastric secretion in rats was studied with pylorus ligation. The effect on gastrointestinal motility was observed by determination of gastric emptying and small intestinal propulsion ability in mouse. RESULTS: SHGP enhanced hot pain threhshold and decreased the number of twisting body in mouse. SHGP markedly inhibited gastric ulcer induced by water immersion stress, reserpine and absolute ethyl alcohol. SHGP significantly inhibited the secretion of gastric acid and pepsin and promoted the secretion of gastric mucus. SHGP markedly delayed gastric emptying in normal mouse and when gastric emptying and small intestinal propulsion was stimulated by neostigmine. SHGP faintly strengthed the effect of atropine on inhibition of gastrointestinal motility. CONCLUSION: Shugan Pills could have analgesic effect, anti gastric ulcer action, it inhibited the secrection of gastric juice and the activity of gastric smooth muscle. These effects might be the pharmacological mechanisms of SHGP on treatment of epigastralgia.

Effect of Zhouluotong on rat's sciatic nerve function and polyol pathway with diabetic peripheral neuropathy / 中成药

AIM:To investigate the effects of Zhouluotong (Radix Astragali, Ramulus Cinnamomi, Radix Angelicae Sinensis, Radix Rchmannia, Herba Asari, etc.) on nerve function and polyol pathway in streptozotocin diabetic rats. METHODS: Streptozotocin diabetic rats were administrated with Zhouluotong for 8 weeks. Effects of drugs on sciatic never morphological alterations, sciatic never conduction velocity, aldose reductase activity, Na +,K + ATPase activity and sciatic nerve polyol contents were determined. RESULTS: Compared with diabetic group, sciatic never morphological alterations was improved, sciatic never conduction velocity was increased, aldose reductase activity was depressed and Na +,K + ATPase activity was increased in each administrated group. Sorbitol and gloucose contents were decreased in Zhouluotong groups. CONCLUSION: Zhouluotong could improve metabolism and function of peripheral nerve issue in streptozotocin diabetic rats. As a result of that, it could prevent diabetic peripheral neuropathy in streptozotocin diabetic rats.

The action of Shuganwan on experimental gastric ulcer / 西安交通大学学报(医学版)

Objective To study the action of Shuganwan(SHGW) on experimental gastric ulcer in mice. Methods The anti-ga stric ulcer action of SHGW was observed on the gastric ulcer induced by water im mersion stress, reserpine and absolute ethyl alcohol. The effect on gastric secr etion in rats was studied by pyloric ligation. The effect on gastrointestinal mo tility was observed by gastric emptying in mice. The analgesic effect was tested by the hot-plate test and writhing method. Results SHGW m arkedly inhibited gastric ulcer induced by water immersion stress, reserpine and absolute ethyl alcohol. SHGW significantly inhibited the secretion of gastric a cid and pepsin and promoted the secretion of gastric mucus. SHGW markedly delaye d gastric emptying in normal mice and when gastric emptying was stimulated by ne ostigmine. SHGW mildly strengthend the effect of atropine on gastric emptying. S HGW enhanced hot pain threshold and decreased the number of twisting body in mic e. Conclusion Shuganwan may have anti-gastric ulcer ac tion. The mechanism of the action might be associated with its inhibition of the secretion of gastric juice, promotion of the secretion of gastric mucus,inhibit ion of activity of gastric smooth muscle and analgetic effect.

Protective action of Shuganwan on acute liver injury and its effect on bile secretion in rats / 西安交通大学学报(医学版)

Objective To study the protective action of Shuganwan on liver injury and its cholagogue action. Methods Acute liver injury was induced by carbon tetrachloride in rats. The biochemical indexes and pathological changes were used for evaluation. The cholagogue action was studied by biliary drainage method. Results Compared with those of the CCl 4 control group, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin levels of Shuganwan group declined significantly, and albumin/ globulin (A/G) inversion was obviously improved. The pathological changes revealed that liver injury was relieved. There was no change in bile secretion after administration of Shuganwan. Conclusion Shuganwan has protective action on acute liver injury by carbon tetrachloride, but no promotive action on bile secretion.