Antimicrobial stewardship program in China’s tertiary hospitals in 2018:a nationwide cross-sectional online survey

In the present study,we aimed to assess the development of the antimicrobial stewardship(AMS)program in China’s tertiary hospitals to identify the potential challenges for the AMS program and provide references and benchmarks for strategic policymaking.A nationwide cross-sectional study was conducted online by sending questionnaires to tertiary hospitals under China Antimicrobial Resistance Surveillance System(CARSS).The questionnaire included 5 sections regarding structure,technical support,antimicrobial use management,antimicrobial use surveillance,and education.Descriptive statistics were used for data analysis.Of the 1044 tertiary hospitals under CARSS,13.4%(140)hospitals participated in the study.Among them,99.3%(139/140)set up the AMS program.The hospital president(82.1%,115/140)and medical service department(59.3%,83/140)were responsible for AMS outcomes in most hospitals.Structured antimicrobial formulary restriction management was adopted by 99.3%(139/140)hospitals.Infectious disease department,infection control department,and microbiological laboratories were established in 87.1%(122/140),99.3%(139/140)and 100%(140/140)hospitals,respectively.Up to 85.6%(124/140)hospitals applied clinical pathways,and 33.6%(47/140)hospitals implemented hospital-specific guidelines for infectious diseases.Outpatient prescription auditing,inpatient prescription auditing,and prophylactic antimicrobial prescription auditing of aseptic operation were performed in 99.3%(139/140),98.6%(138/140)and 95.7%(134/140)hospitals,respectively.Up to 97.1%(136/140)hospitals participated in antimicrobial use surveillance network,and 99.3%(139/140)hospitals established the specialized management of carbapenem and tigecycline.Staff education and public education were provided with various ways and frequencies in 100%(140/140)and 90.0%(126/140)hospitals,respectively.AMS programs in China’s tertiary hospitals were primarily headed by hospital presidents and involved collaboration among various disciplines and administrative departments.More efforts should be put to further promote and strengthen the development of hospital-specific guidelines and the establishment of a progress and outcome evaluation system.

2003–2020年中国仿制药上市和新药市场独占期研究

中国近期提出给予新药、孤儿药和儿科药物6年的数据保护期,以鼓励相关药物的研发创新。本研究评估了2003至2020年在中国批准上市的356种新小分子药物的仿制药上市情况和市场独占期。所有新药中,155个(43.5%)新药有仿制药上市,市场独占期中位数为5.6(四分位数:2.4–9.4)年。进口药物、口服缓释药物和神经系统药物比其它药物的仿制药上市比例更高(P<0.001,P=0.039,P<0.001)。国产药品的市场独占期中位数比进口药品更长(8.4 vs 5.7年)。市场独占期中位数从抗肿瘤和免疫调节剂的3.6年到消化道和代谢药物的6.8年不等。如果获得6年的数据保护期,新药的市场独占期中位数预计将增加一倍。较长的市场独占期可能降低患者药品可及性,政府在制定相关政策时应考虑在鼓励创新和确保药品可及性间寻求平衡。

Investigations and feedback on the training mode of professional master's degree of clinical pharmacy in Peking University and the preliminary exploration of Pharm. D. Education

In order to carry out the comprehensive reform of the professional master’s degree training mode of clinical pharmacy, we carried out interviews among 91 persons on the professional master’s degree of clinical pharmacy in Peking University School of Pharmaceutical Sciences and collected extensive feedback. We preliminaries explore the mode of Doctor of Pharmacy（Pharm. D.） Education, laying the foundation for Doctor’s education of professional clinical pharmacy in China. We conducted investigations and interviews among 91 clinical pharmacists and students of Peking University School of Pharmaceutical Sciences on the training of professional master’s degree and Pharm. D. education mode, which includes 67 postgraduates and 24 clinical pharmacists. Respondents put forward the problems of training mode and corresponding suggestions and opinions from different aspects during the investigation and interview. The results mainly divide into four aspects： curriculum setting, clinical practice, assessme nt system and teaching resources. Respondents put forward effective feedback on the above four aspects, which are beneficial to the comprehensive reform of the training mode of professional master degree in clinical pharmacy and preliminary exploration of Pharm. D. Education in China.

Prevalence and influence factors of self-medication in Chinese middle-aged and elderly people: evidence from 2011, 2013 and 2015 CHARLS panel data

Self-medication is an increasingly frequent phenomenon worldwide and has an important influence on health.In this study,we analyzed the self-medication prevalence rate in Chinese middle-aged and elderly people,and explored the influence factors.The data from China Health and Retirement Longitudinal Study(CHARLS)in 2011,2013 and 2015 were used.Self-medication prevalence was calculated as the number of whole people divided by the number of people taking self-medication.The influence factors of self-medication were analyzed by panel data random effect model.We excluded observations with missing values in our analysis,leaving 16 962,17 876 and 19 572 observations in 2011,2013 and 2015,respectively.The average 3-year self-medication prevalence was 45.52%.Moreover,11.70%of respondents practiced self-medication with prescription medicine in 2011,2013 and 2015.Respondents living in non-rural areas(P=0.009)and western region(P=0.000)took more self-medication.Self-medication was a common phenomenon among middle-aged and elderly population in China.The government should strengthen the guidance for the middle-aged and elderly people who took more self-medication,such as those living in urban and western region.

中国中老年癌症幸存者健康状况分析

中国癌症幸存者的数量正在不断增长,这一人群的健康问题是我国卫生系统所面临的一项严峻挑战。本研究概述了中国中老年癌症幸存者的健康状况,并探究癌症史与健康状况之间的关系。本研究基于中国健康与养老追踪调查(CHARLS)数据识别癌症幸存者和无癌症史的受访者,利用2018年的调查数据评估两组患者的自评健康状况、抑郁状况和日常生活活动能力并采用卡方检验和Logistic回归进行组间分析。本研究纳入了447名癌症幸存者和19051名没有癌症史的受访者。与无癌症史的受访者相比,癌症幸存者的自评健康状况更差、抑郁和日常生活活动能力受损的比例也更高。在调整了受访者的社会人口学特征和疾病与健康行为之后,我们发现癌症史与更糟糕的自评健康状况(OR 1.62;95%CI,1.38–1.96,P<0.001)、更高的抑郁风险(OR 1.21;95%CI,1.10–1.34,P<0.001)和日常生活活动能力受损(OR 1.43;95%CI,1.29–1.58,P<0.001)显著相关。研究表明,我国45岁以上癌症幸存者的生理和心理健康状况较差,需要为他们提供更周到的支持与照顾。

An analysis on the factors associated with reuse of insulin pen needles in type 2 diabetic patients in China

Incorrect injection technique of insulin is a common problem worldwide,which can reduce the efficacy of insulin therapy and lead to poor glucose control.A cross-sectional,multiple-center survey from 44 hospitals was conducted from Nov.2015 to Dec.2015.Non-parametric Kruskal–Wallis analysis of variance and Mann-Whitney U test were used for multi-parametric analysis.Multivariable logistic regressions were performed to identify the factors associated with independent variables.Overall,a single needle was used at an average of 3.79 times,with the highest of 60 times.Analysis across all study participants showed that the frequency of a single needle was positively correlated with age（P = 0.029）,duration of diabetes（P≤0.001） and number of complications（P≤0.001）.Multivariable logistic regressions analysis of insulin pen needle reuse and needle compliance showed that age,income,education,marital status,duration of diabetes,quality of life and cost of drug were significantly related to needle reuse.From this survey,we found that reuse of insulin pen needle was common in China.Frequency of needle reuse was related to the patients＇ demographic characteristics（income level,age,region,education,employment status and self-care）,health-related variables（duration of diabetes,number of complications and EQ-5 D index scores） and utilization of health services（clinical visits,hospitalization and cost of medications）.

Trends of consumption and expenditure of antibacterial traditional Chinese medicine in secondary and tertiary hospitals in China:an analysis of pharmaceutical sales data,2011–2015

Traditional Chinese medicines(TCMs)are commonly used in China,and some of them have been proved to be effective against infection caused by certain pathogenic bacteria.In the present study,we aimed to describe the trends of antibacterial-effect traditional Chinese medicine(AeTCM)consumption and expenditure in secondary and tertiary hospitals in China using pharmaceutical sales data from January 2011 to December 2015.Aggregated monthly surveillance data on AeTCM sales in China’s hospitals were retrospectively analyzed.Population weighted daily define doses,which are the recommended daily amounts based on dosage regimen recommended in the manufacturers’instructions,were adopted.The AeTCM consumption was expressed in DDD per 1000 inhabitants per day(DID).The AeTCM expenditure was expressed in US dollars.A compound annual growth rate(CAGR)was used to describe the growth of AeTCM consumption and expenditure.A total of 1293 AeTCMs were matched and analyzed from 468 tertiary hospitals and 114 secondary hospitals from 28 provinces.The total AeTCM consumption and expenditure demonstrated a significant upward trend during the study period from 4.07 DID to 6.82 DID with a CAGR of 13.75%,and 839.75 million US dollars to 1276.82 million US dollars with a CAGR of 11.04%,respectively.Compared with eastern provinces,the consumption of AeTCMs was higher in the central and western provinces.Parenteral AeTCMs accounted for 7.20%of the total Ae TCM consumption,but nearly 45%of the total AeTCM expenditure.The AeTCM use in China demonstrated a rapid growth,which could be the result of the substitutional effect from antimicrobial stewardship and brought a potential risk of overuse.More studies are needed to further explore the potential efficacy of AeTCMs as an alternative approach towards infection treatment and to help confine antimicrobial resistance.

Medical service utilisation, economic burden and health status of patients with rare diseases in China

Many patients with rare diseases not only suffer from more severe conditions but often receive less disease management, which is one significant public health concern globally. Few practice-based surveys focus on the care of patients with rare diseases. In the present study, we aimed to investigate medical service utilization, economic burden and health status of patients with rare diseases in China. A cross-sectional questionnaire survey focusing on patients with rare diseases was conducted. Descriptive analysis was conducted to examine the sociodemographic characteristics, medical service utilization, economic burden and health status. Logistic regression analysis was applied to explore influencing factors of self-rated health. A total of 982 patients with 81 types of diseases were included in this survey. We found that 58.2% of patients experienced misdiagnosis, and 35.2% of the patients were misdiagnosed for at least five times. Moreover, 65.8% of patients traveled to hospitals to seek medical services, and 92.1% of patients paid expenses for their treatment. However, only 1.3% of patients could afford their medical expenditure without debts, and 86.8% of patients regarded their health status as bad or moderate. Significant factors correlated with health status were economic status, gender, age, employment and household size. From this study, the accessibility of medical service utilization, the affordability of medical economic burden, and the condition of health status for patients with rare disease in China were considerably poor. Basic medical insurance did not play its role in improving the utilization of medical services and the affordability of medical costs. Social support should be encouraged to improve patients＇ health status.

The impacts of national essential medicine policies on the rational use of medicines in China: A cross-sectional study in primary health care institution

Irrational use of medicines is a major problem worldwide, and it is believed there would be positive correlation between the National Essential Medicines Policies(NEMPs) and the level of rational use of medicines(RUMs). Though there is some early evidence on the NEMPs’ effects on RUMs in China, the evidence is scarce, and conclusions vary. In the present study, we aimed to evaluate the impacts of the NEMPs of China on the RUMs in the primary health care institutions(PHCs). A cross-sectional survey was conducted in 2010. A total of 201 PHCs from six provinces of China were selected, and 39 181 prescriptions were extracted from January to June, 2010. Six indicators were used and tested by independent-samples T test. We found that the average number of drugs per prescription in PHCs with NEMP implementation(the treatment group) was significantly higher than that of the group without NEMP implementation(the control group)(3.37 vs. 2.83, P<0.01). There was no significant difference in the average cost per prescription(81.43 vs. 75.02). The percentage of prescriptions, including an antibiotic(53.40% vs. 36.48%, P<0.01) or an injection(40.54% vs. 27.94%, P<0.01), was higher in the treatment group, and the percentage of drugs prescribed by general name was significantly lower(83.71% vs. 93.11%, P<0.01). For the percentage of drugs prescribed from essential medicines list, the treatment group exhibited the higher ratio(76.12% vs. 53.45%, P<0.01). From this study, the NEMPs were not likely to have a positive impact on RUMs. China still needed efforts to improve the selection, the absence of physicians’ active involvement, and the patients’ habits of irrational medication use.

Impact of the zero-markup drug policy on volume of medical service:based on 57 county hospitals of China

In the present study,we aimed to assess the long-term impact of zero-markup drug policy on volume of medical service in county hospitals of China.This study used 57 county hospitals’records of medical service from 2011 to 2015,and a fixed effect model was applied to examine the impact of the zero-markup drug policy on volume of medical service.The outcome indicators included the number of patient visits,the number of prescriptions,the number of discharged patients,the length of stay,the number of patients who had surgeries and the number of patients who had CT or MRI,monthly.The number of hospitals which implemented the zero-markup drug policy was increased continuously.By the end of 2015,41 hospitals(71.9%)implemented this policy.The panel regression showed that most indicators were insignificantly decreased,including the number of patient visits(P<0.01),the length of stay(P<0.05),the number of patients who had surgeries(P<0.01)and the number of patients who had CT or MRI(P<0.01).However,the number of prescriptions and the number of discharged patients were not significantly changed.The implementation of the zero-markup drug policy might affect the reduction of the volume of medical service in county-level hospitals and the reason needs to be clarified in future studies.

Pharmacists’perceptions of generic drugs in China

Perceptions of Chinese pharmacists towards generic drugs were evaluated by a cross-sectional study from Aug.2018 to Dec.2018.Online survey tool Sojump was adopted to release the questionnaires using convenience sampling.A total of 577 questionnaires by pharmacists were analyzed.A meaningful proportion of pharmacists expressed negative perceptions of generic drugs,such as perceiving generics as less effective,less safe and more likely to cause side effects compared to their branded equivalents.Educational campaigns that focus on misperceptions of generic drugs may be necessary.

HPLC-MS/MS quantification of the HIV-1 protease inhibitor saquinavir in mice plasma and brain

In the present study, a rapid and sensitive liquid chromatography-tandem mass spectrometric method for the determination of saquinavir in mice plasma and brain was developed, validated, and applied to a preliminary screening study evaluating the effect of bioflavonoids on the brain distribution of saquinavir in mice. Saquinavir and the internal standard（ritonavir） were isolated from plasma and homogenized brain tissue matrices using a liquid-liquid extraction procedure, and the chromatographic separation was accomplished by using a reversed phase C18 column（150 mm×2.1 mm, 5.0 μm）. The analyte was detected by a triple-quadrupole tandem mass spectrometer via electrospray ionization, and multiple reaction monitoring was employed to select both saquinavir and ritonavir in the positive ion mode. A linear dynamic range of 0.1–10 ng/m L for plasma samples was established and the lower limit of quantification was 0.1 ng/m L. The intra- and inter-day precision were 7.5%–12.1%, and the accuracies ranged from 90.5% to 107.2% for plasma. A linear dynamic range of 0.1–10 ng/g for brain samples was established and the lower limit of quantification was 0.1 ng/g. The intra- and inter-day precision were 7.3%–11.9%, and the accuracies ranged from 90.8% to 107.4% for brain tissue samples. This method was successfully applied a preliminary screen of 19 bioflavonoids on the brain distribution of saquinavir in mice, and biochanin A shows the strongest effect.

The comprehensive influence of firm-level factors on drug product internationalization of Chinese pharmaceutical firms

Drug product internationalization（DPI） can be affected by multiple firm-level factors. However, existing studies mainly focus on a single or several factors and the deviation generated by the factors＇ effects on each other has been neglected. We aimed to study the comprehensive influences of firm-level factors on Chinese pharmaceutical firms that chose the DPI mode. Student＇s t tests and Chi Square tests were used to explore the differences between firms with or without DPI modes. Then, logistic regression analysis was used to explore the comprehensive impacts of these 16 variables. Through empirical research, we found the factors influencing the DPI mode of Chinese pharmaceutical enterprises and the firm-level factors that influenced DPI mode selection. This study showed that the capacity of enterprise＇s innovation and knowledge absorption were related to the mode selection. Moreover, the education of the top management team significantly contributed to the DPI mode selection of pharmaceutical firms. This study also provided theoretical and empirical evidence for pharmaceutical enterprises when choosing their DPI mode. The internationalization of Chinese pharmaceutical firms remained at the early stage. However, the internationalization of drug products from China would affect the international pharmaceutical supply in the long term.

Trends on medicine use in county public hospitals in Sanming,China from 2011 to 2017

Sanming model in healthcare reform has attracted much attention due to its comprehensive and efficient exploration,while its impact on physicians’prescribing behavior remains unknown.In the present study,we aimed to evaluate the impact of Sanming reform on physicians’medicine use in county-level public hospitals.We collected outpatient prescriptions in the internal medicine and pediatric departments from nine county public hospitals in Sanming from January 2011 to December 2017.We used six prescribing indicators to analyze physicians’medicine use.The Mann-Kendall test was used to examine trends in the study outcomes.A total of 1577904 outpatient prescriptions were included in this study.The average prescription rate of antibiotics and combined antibiotics were 57.5%and 12.2%in 2011,respectively,which were declined to 28.2%(P=0.007)and 2.9%(P=0.003)in 2017,respectively.The average prescription rate of injection was 30.2%in 2011 and declined to 5.3%(P=0.003)in 2017.As for the subgroup analysis of the internal medicine and pediatric departments,the average prescription rate of antibiotics was 39.3%and 71.4%in 2011,respectively,which was declined to 10.2%(P=0.003)and 47.3%(P=0.035)in 2017,respectively.The average prescription rate of combined antibiotics was 15.9%and 9.4%in 2011,respectively,which was declined to 2.9%(P=0.003)and 2.9%(P=0.016),respectively.The average prescription rate of injection was 17.8%and 39.6%in 2011,respectively,which was declined to 1.9%(P=0.003)and 9.0%(P=0.003),respectively.Our study showed a significant decreasing trend in antibiotic use in county-level public hospitals after the Sanming healthcare reform,indicating that the reform successfully promoted the appropriate use of medicine to some extent.

Association between CYP3A4 gene polymorphisms and clopidogrel response in patients with cardio-cerebrovascular diseases:a systematic review and Meta-analysis

CYP3A4 plays a critical role in clopidogrel activation in the liver.The polymorphism of CYP3A4 may have an important effect on clopidogrel response in patients with cardio-cerebrovascular diseases.We conducted a systematic review and meta-analysis to evaluate the impact of CYP3A4 polymorphism on platelet reactivity after clopidogrel treatment and the outcomes of patients.A systematic literature search(up to 7th October,2019)was performed on the PubMed,EMBASE,Cochrane Library,clinicaltrials.gov,and Chinese databases,including China National Knowledge Infrastructure(CNKI)and Wan Fang Data.Cohort studies or case-control studies evaluated platelet reactivity and patients‟outcomes in different genotype patients.The Review Manager software was used for data analysis,and the NOS scale was used to assess the quality of included studies.A total of 18 articles were included in the Meta-analysis.The results showed the platelet reactivity after clopidogrel administration had no significant difference between CYP3A4 variant carriers and non-carriers.The occurrence of composite ischemic events or stent thrombosis had no significant difference between CYP3A4 variant carriers and non-carriers,either.In conclusion,there was no significant association between CYP3A4 polymorphism and clopidogrel response in patients with cardio-cerebrovascular diseases.

The impact of the provincial reimbursement scheme on the use of targeted anticancer medications in Zhejiang,China:a controlled interrupted time-series analysis

To alleviate problems with access and affordability,six targeted anticancer medications(TAMs)were listed in the Provincial Reimbursement Drug List(PRDL)for the first time in Zhejiang,China in February 2015.In the present study,we aimed to evaluate the implementation of the PRDL policy on TAMs use.Using the pharmaceutical procurement data of these six listed TAMs(study group)and four unlisted TAMs(control group)from 22 tertiary hospitals in Zhejiang,China dated between January 2014 and February 2017,interrupted time-series analysis was adopted to examine differences in the average hospital purchasing volume(HPV)and the average hospital purchasing spending(HPS)between the two groups.The average daily cost of listed TAMs in the study group was decreased after April 2015.After enlistment,the average HPV per month was significantly increased by 34.6 defined daily doses(DDDs)(P<0.001),and the average HPS per month was significantly increased by USD 6614.9(P<0.001)for the listed TAMs in the study group(n=6).Neither the average HPV nor the average HPS changed significantly for the unlisted TAMs in the control group(n=4).The PRDL policy showed positive effects on improving patients’affordability and promoting access to TAMs in Zhejiang.The government should conduct further price negotiations and include more TAMs with clinical benefits into reimbursement schemes to relieve patients’financial burden and promote access.

Anticancer medicines in China: Trends in daily therapy cost and relative procurement volume and spending

Dear editors,Cancer is a critical public health concern worldwide.The number of cancer patients in developing countries accounts for ∼50% of the total number of cancer patients worldwide,however,over 70% of cancer deaths are from developing countries[1].In China,cancer has been a leading cause of death since 2010,with a substantially lower 5-year survival rate,compared to developed countries[2].