Evidence-based expert consensus on clinical management of safety of Bruton’s tyrosine kinase inhibitors(2024)

Bruton’s tyrosine kinase inhibitors(BTKis)have revolutionized the treatment of B-cell lymphomas.However,safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy.A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment.A multidisciplinary consensus working group was established,comprising 35 members from the fields of hematology,cardiovascular disease,cardio-oncology,clinical pharmacy,and evidencebased medicine.This evidence-based expert consensus was formulated using an evidence-based approach and the Delphi method.The Joanna Briggs Institute Critical Appraisal(JBI)tool and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)approach were used to rate the quality of evidence and grade the strength of recommendations,respectively.This consensus provides practical recommendations for BTKis medication based on nine aspects within three domains,including the management of common adverse drug events such as bleeding,cardiovascular events,and hematological toxicity,as well as the management of drug-drug interactions and guidance for special populations.This multidisciplinary expert consensus could contribute to promoting a multi-dimensional,comprehensive and standardized management of BTKis.

Optimize the combination regimen of Trastuzumab and Nab-paclitaxel in HER2-positive tumors via modulating Caveolin-1 expression by lovastatin

The combination regimen of trastuzumab(Tras)plus Nab-paclitaxel(Nab)is recommended to treat HER2-positive(HER2+)cancers.However,they exert effects in different mechanisms:Tras need to stay on cell membranes,while Nab need to be endocytosed,therefore the concurrent combination regimen may not be the best one in HER2+tumors treatment.Caveolin-1(Cav-1)is a key player in mediating their endocytosis and is associated with their efficacy,but few researches noticed the opposite effect of Cav-1 expression on the combination efficacy.Herein,we systematically studied the Cav-1 expression level on the combination efficacy and proposed an optimized and clinically feasible combination regimen for HER2+Cav-1 High tumor treatment.In the regimen,lovastatin(Lova)was introduced to modulate the Cav-1 expression and the results indicated that Lova could downregulate Cav-1 expression,increase Tras retention on cell membrane and enhance the in vitro cytotoxicity of Tras in HER2+Cav-1 High cells but not in HER2+Cav-1 Low cells.Therefore,by exchanging the dosing sequence of Nab and Tras,and by adding Lova at appropriate time points,the precise three-drug-sequential regimen(PTDS,Nab(D1)-Lova(D2)-Lova&Tras(D2+12 h))was established.Compared with the concurrent regimen,the PTDS regimen exhibited a higher in vitro cytotoxicity and a stronger tumor growth inhibition in HER2+Cav-1 High tumors,which might be a promising combination regimen for these patients in clinics.

A Protocol for Developing a Clinical Practice Guideline for Therapeutic Drug Monitoring of Vancomycin

This study aimed to develop a guideline for therapeutic drug monitoring（TDM） of vancomycin. We adopted the new guideline definition from the Institute of Medicine（IOM）, adhered closely to the six domains of the Appraisal of Guidelines for Research ＆ Evaluation Ⅱ（AGREE Ⅱ）, and made recommendations based on systematic reviews. We established a Guideline Steering Group and a Guideline Development Group, formulated 12 questions in the form of Population, Intervention, Comparison, Outcome（PICO） and completed a literature search. As far as we know, we will develop the first evidenced-based guideline for vancomycin TDM under the framework of the Grade of Recommendations Assessment, Development and Evaluation（GRADE）.

Construction of an intelligent patient satisfaction assessment system and its application in emergency management

Hospital emergency management work is of great importance which not only related to the life and health of the people but also related to social stability.It is necessary to construct and improve the patient satisfaction assessment system so that doctors and patients can interact in a timely and effective manner,and the hospital can alert or respond promptly.This study constructs a closed-loop emergency management system consisting of patient-end,data center and decision-making-end,and apply the feedback information to hospital emergency management.In the preliminary applications,the system has a significant effect on the hospital emergency management mechanism.The researchers will improve the system in the follow-up study。

Pregabalin induced balance disorder,asthenia,edema,and constipation in an elderly adult:A case report

BACKGROUND Pregabalin is widely used to treat neuropathic pain associated with postherpetic neuralgia.To our knowledge,this is the first report on simultaneously occurring dose-related adverse drug reactions(ADRs)of balance disorder,asthenia,peripheral edema,and constipation in an elderly patient after pregabalin.CASE SUMMARY A 76-year-old female with a history of postherpetic neuralgia was prescribed pregabalin(300 mg daily).After taking pregabalin for 7 d,the patient developed balance disorder,weakness,peripheral pitting edema(2+),and constipation.On days 8-14,the pregabalin dose was reduced to 150 mg/d based on creatinine clearance.The patient’s peripheral edema improved significantly with the disappearance of all other adverse symptoms.On day 15,the pregabalin dose was increased to 225 mg/d to relieve pain.Unfortunately,the symptoms mentioned earlier gradually reappeared after 1 wk of pregabalin treatment.However,the complaints were not as severe as when taking 300 mg/d pregabalin.The patient consulted her pharmacist by telephone and was advised to reduce the dose of pregabalin to 150 mg/d and add acetaminophen(0.5 g,q6h)to relieve pain.The patient’s ADRs gradually improved over the following week.CONCLUSION Older patients should be prescribed a lower initial dose of pregabalin.The dose should be titrated to the maximum tolerable dose to avoid dose-limiting ADR.Dose reduction and the addition of acetaminophen may help limit ADR and improve pain control.

International collaboration to promote global health:The 2017 Belt and Road Initiative Global Health International Congress&2017 Chinese Preventive Medicine Association--Chinese Society on Global Health Annual Meeting

With the rapid development of new technologies and global trade and increasing collaboration am ong countries worldwide,public health has become a global issue.Global health,as a new discipline,has been drawing more attention from both academ ia and governments.The Belt and Road Initiative(BRI),proposed by China in 2013,aimed to prom ote trade and resource exchange,including education,research,and health issues,with over 60 countries in Asia,Africa,and Europe.The BRI provides good opportunities for involved countries to address health problems jointly as well.In response to the BRI and to promote international collaboration on global health issues,"The 2017 Belt and Road Initiative Global Health International Congress&2017 Chinese Preventive M edicine Association-Chinese Society on Global Health Annual Meeting"was held on Septem ber 24-27,2017 in Xi’an,China.Thus far,this is the largest high-quality international conference held in China that focused on the BRI global health issues.This article summarized the background,key sessions and topics covered during the congress,and important events,and highlights different perspectives of the BRI and global health by invited experts from China and abroad.The conference included 14 sessions(three keynote speech forums and ten scientific sessions and a research poster session)and about 100 speakers,around 40 of which were leading experts outside of China.All the major sessions were held in English.More than 40 leaders and experts of health sectors from 13 countries presented their work in the congress.Approximately 400 delegates from 29 countries attended the congress.Delegates had extensive discussions about global health related issues,future cooperation and development in global health.The congress fostered international exchange and collaboration.

Research on Hospital Medical Crisis Management Based on 4R Theory: A Case Study of the Crisis Event in the Second Affiliated Hospital of Harbin Medical University

The hospital medical crisis management is the strategy adopted by hospitals for medical crisis.It aims to minimize the loss brought about by medical crisis to the hospital through management.By using 4R theory of crisis management and taking the incident of"sky-high medical expenses"happened in Second Affiliated Hospital of Harbin Medical University as an example,we study how to improve and perfect the medical crisis management strategy of hospitals in our country.As a result,we think hospitals can improve the crisis management strategy from four aspects of curtailment,preparation,reaction and resilience,so as to solve this issue appropriately,protect the legitimate rights and interests of patients to the greatest extent and promote the sustainable development of the hospital.

Going-out Behaviors of Patients with Chronic Diseases When Purchasing Drugs During Covid-19

Objective:This study sheds light on the going-out behaviors of patients with chronic diseases when purchasing drugs during COVID-19,explores what factors influence these behaviors,and makes recommendations to guarantee the pharmaceutical treatment of patients with chronic diseases.Methods:A questionnaire based on the health belief model(HBM)was designed and convenience sampling was employed to administer the online questionnaires.The influence of the respondents’demographic information on their going-out behaviors was analyzed by means of multiple linear regression.A structural equation model(SEM)was constructed to explore how health beliefs related to chronic diseases and COVID-19 influenced patients’going-out behaviors.Results:A total of 869 questionnaires were analyzed.The structural equation model revealed that while the severity of the chronic disease had a direct positive effect on going-out behaviors(l=0.106),chronic disease behavior barriers had a direct negative effect on their going-out behaviors(l=-0.204).Conclusion:Educational background,co-living situation,and income could influence patients’going-out behaviors.The severity of the chronic disease and chronic disease behavior barriers directly affected patients’going-out behaviors.Furthermore,patients’health beliefs about COVID-19 ultimately affected their going-out behaviors by influencing their health beliefs related to chronic disease.

Liuwei Dihuang Pills(六味地黄丸) Enhance the Effect of Western Medicine in Treating Type 2 Diabetes:A Meta-Analysis of Randomized Controlled Trials

Objective： To perform meta-analyses evaluating the efficacy of adding Liuwei Dihuang Pills （六味地黄丸 LDP） to Western medicine in improving treatment outcomes for type 2 diabetes. Methods： Medline, PubMed, Cochrane Library, and Chinese databases, including the Chinese National Knowledge Infrastructure were searched to identify eligible studies; i.e., if the study involved a randomized clinical trial in which the experimental group combined LDP with Western drugs and the control group used the corresponding Western drugs alone to treat type 2 diabetes. Outcomes were measured in terms of fasting blood glucose （FBG）, postprandial blood glucose （2hPG） and HbAlc level. Efficacy was also measured by using control and response rates. The combined odds ratio （OR）, mean difference （MD）, and 95% confidence intervals （95% CI） were calculated. Results： Studies included in the analysis were less adequate than expected in terms of methodological qualify. A total of 1,609 patients from 18 studies were included. We found that adding LDP can lower patients＇ FBG （MD=0.54 mmol/L, 95% CI [0.15, 0.93], P=0.007）, 2hPG （MD=1.05 mmol/L, 95% CI [0.29, 1.81], P〈0.01） and HbAlc （MD=0.23, 95% CI [0.02, 0.45], P=0.008）. There were also improvements in treatment response rates （OR=3.41, 95% CI [2.38, 4.90], P〈0.01） and control rates （OR=2.47, 95% CI [1.91, 3.20], P〈0.01）. Conclusion： Adding LDP to Western medicine might improve treatment outcomes of diabetes, including FBG, 2hPG, response rates and control rates.

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.

The role of caveolin-1 in the biofate and efficacy of anti-tumor drugs and their nano-drug delivery systems

As one of the most important components of caveolae,caveolin-1 is involved in caveolaemediated endocytosis and transcytosis pathways,and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal transduction.In recent years,the relationship between the expression level of caveolin-1 in the tumor microenvironment and the prognostic effect of tumor treatment and drug treatment resistance has also been widely explored.In addition,the interplay between caveolin-1 and nano-drugs is bidirectional.Caveolin-1 could determine the intracellular biofate of specifc nano-drugs,preventing from lysosomal degradation,and facilitate them penetrate into deeper site of tumors by transcytosis;while some nanocarriers could also affect caveolin-1 levels in tumor cells,thereby changing certain biophysical function of cells.This article reviews the role of caveolin-1 in tumor prognosis,chemotherapeutic drug resistance,antibody drug sensitivity,and nano-drug delivery,providing a reference for the further application of caveolin-1 in nano-drug delivery systems.

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.

The efficacy and safety of three types of combination therapies in patients with moderate to very severe COPD: a systematic review and meta-analysis

Inhaled drugs,including long-acting muscarinic antagonists(LAMAs),long-actingβ2-agonists(LABAs)and inhaled corticosteroids(ICSs),are the main therapeutic options for patients with chronic obstructive pulmonary disease(COPD).We conducted a systematic review and meta-analysis to compare the efficacy and safety of LAMA+LABA+ICS,LAMA+LABA and LABA+ICS therapies.The Pubmed,Embase and Cochrane Library databases were searched for randomized controlled trials(RCTs)comparing the efficacy(moderate-to-severe exacerbations,lung function and quality of life)and safety(adverse events(AEs),severe adverse events(SAEs),withdrawals due to AEs,deaths and pneumonia)of LAMA+LABA+ICS,LAMA+LABA and LABA+ICS in COPD patients.Two investigators independently searched eligible studies and extracted relevant information.The data were analyzed using the Review Manager software,and the quality of included studies was assessed using the Cochrane risk of bias tool.A total of 27 studies were included,and majority of the studies showed low risk of bias.Moderate-to-severe exacerbations were lower after LAMA+LABA+ICS therapy compared with the LABA+ICS(RR=0.66;95%CI:0.59–0.74)and LAMA+LABA therapies(RR=0.88;95%CI:0.82–0.94).Lung function was significantly improved after LAMA+LABA+ICS compared with LAMA+ICS treatment.FEV1,peak FEV1 and trough FEV1 were significantly increased by 100 mL,150 mL and 120 mL,respectively,in LAMA+LABA+ICS therapy compared with LAMA+ICS.In addition,LAMA+LABA therapy resulted in increased FEV1,peak FEV1 and trough FEV1 by 80 mL,90 mL and 70 mL,respectively,compared with LAMA+ICS.SGRQ-total score was used to assess quality of life of COPD patients,which indicated that LAMA+LABA+ICS therapy was associated with slightly greater decrease compared with LABA+ICS(MD=–1.33;95%CI:–2.35 to–0.30).No significant differences were found across all three treatment combinations in term of AEs,SAEs,withdrawals due to AEs and deaths.However,the risk of pneumonia was higher in the triple therapy group than that in the LABA+ICS(RR=1.16;95%CI:1.01–1.33)or LAMA+LABA(RR=1.31;95%CI:1.06–1.62)groups,and significantly lower in the LAMA+LABA group compared with LABA+ICS(RR=0.64;95%CI:0.54–0.76).LAMA+LABA+ICS therapy offered greater efficacy and comparable safety compared with the LAMA+LABA or LABA+ICS therapies.However,triple therapy could increase the risk of pneumonia compared with LAMA+LABA or LABA+ICS therapies.People who have higher risk of pneumonia should carefully consider the use of triple therapy.LAMA+LABA therapy offered greater efficacy and lower risk of pneumonia to LABA+ICS therapy.Collectively,LAMA+LABA therapy might be a better choice than LABA+ICS.

Additive effect of α-ketoacids in chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials

α-Ketoacids （KAs） are widely used in chronic kidney disease （CKD）, but their efficacy is not clear. Therefore, we conducted a systematic review of the benefits of KAs. Two reviewers independently searched MEDLINE, EMBASE, the Cochrane library （http：//www.cochrane.org）, CNKI, and Wan Fang databases from inception to May 31, 2016 for randomized controlled trials （RCTs） comparing K.As plus low protein diet （LPD） with LPD only on CKD patients. Statistical analyses were performed using both a random effects model and a fixed effects model with Rev Man 5.3, followed by sensitivity analysis. We identified 21 randomized controlled trials that enrolled a total of 1448 patients. 726 had received LPD plus KAs and 722 had received only LPD. Compared with simply using of LPD, combining with KAs could decrease serum creatinine （95% CI, 0.46-0.96; P〈0.00001）, serum cholesterol （95% CI, 0.24±3.77; P = 0.02）, serum LDL cholesterol （95% CI, 0.12-0.54; P = 0.31）, and serum triglyceride （95% CI, 0.28--0.83; P = 0.02） while increasing serum HDL cholesterol （95% CI, -1.73-0.07; P〈0.00001）. Likewise, a decrease in p3 （95% CI, 0.90-1.26; P〈0.00001） and PTH （95% CI, 0.70-1.21; P = 0.007） were observed. No hypercalcemia and other ARD or toxicity was reported, which indicated the safety of KAs. Nevertheless, the studies were pooled with considerable heterogeneity. In patients with CKD, there was low-quality evidence suggesting that KAs may perform an additive effect on the improvement of renal function, lipid profile, as well as the correction of calcium-phosphate metabolism disorders. On account of the considerable heterogeneity of the meta-analysis and the costly price and adherence of KAs administration, K.As＇ roles in the management of mild or moderate CKD patients may need more RCTs of large scale and high quality to confirm.

Regulation of online pharmacies in China:the current situation and suggested improvements

Through literature research, expert investigation, and stakeholder interviews, this article summarizes related regulation policies and industry developments of China＇s online pharmacies. Based on the main problems, suggestions to improve the regulatory policies of online pharmacies in China were put forward regarding prescriptions, pharmaceutical services, medical insurance, and drug delivery.

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.

Determinants and Equity Evaluation for Health Expenditure Among Patients with Rare Diseases in China

Background： China has not established social security system for rare diseases. Rare diseases could easily impoverish patients and their families. Little research has studied the equity and accessibility of health services for patients with rare diseases in China. This study aimed to explore the factors that influence health expenditure of rare diseases and evaluate its equity. Methods： Questionnaire survey about living conditions and cost burden of patients with rare diseases was conducted. Individual and family information, health expenditure and reimbursement in 2014 of 982 patients were collected. The impact of medical insurance, individual sociodemographic characteristics, family characteristics, and healthcare need on total and out-of-pocket （OOP） health expenditures was analyzed through the generalized linear model. Equity of health expenditure was evaluated by both concentration index and Lorenz curve. Results： Of all the surveyed patients, 11.41% had no medical insurance and 92.10% spent money to seek medical treatment in 2014. It was suggested female （P = 0.048）, over 50 years of age （P = 0.062）, high-income group （P = 0.021）, hospitalization （P- 0.000）, and reimbursement ratio （RR） （P = 0.000） were positively correlated with total health expenditure. Diseases not needing long-term treatment （P = 0.000） was negatively correlated with total health expenditure. Over 50 years of age （P = 0.065）, high-income group （P = 0.018）, hospitalization （P = 0.000） and having Urban Employee Basic Medical Insurance （UEBMI） （P - 0.022） were positively correlated with OOP health expenditure. Patient or the head of the household having received higher education （P = 0.044 and P = 0.08 l） and reimbursement ratio （P = 0.078） were negatively correlated with OOP health expenditure. The equity evaluation found concentration indexes of health expenditure before and after reimbursement were 0.0550 and 0.0539, respectively. Conclusions： OOP health expenditure of patients with UEBMI was significantly more than that of patients without medical insurance. However, for any other medical insurance, there was no difference between OOP health expenditure of the insured patients and patients without insurance. The current reimbursement policies have increased the equity of health expenditure, but are biased toward high-income people.

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.

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.