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OBJECTIVE To evaluate the effects of gene polymorphism on the efficacy and safety of citalopram/escitalopram， and to provide evidence-based reference for precision medication. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， Wanfang data and SinoMed， clinical studies about the association of gene polymorphism with efficacy and safety of citalopram/escitalopram were collected. Meta-analysis was performed with RevMan 5.3 software after literature screening， data extraction and quality evaluation based on Newcastle-Ottawa scale. RESULTS Totally 35 pieces of literature were included， all of which were cohort studies， with a total of 9 836 patients. Meta-analysis showed that the SLC6A4 gene 5-serotonin transporter linked polymorphic region （HTTLPR） LL genotype was associated with high response rate of citalopram/escitalopram [LS/SS vs. LL： OR＝0.47， 95%CI （0.22， 0.98）， P＝0.05]； results of subgroup analysis suggested a higher correlation in white people with LL genotype and escitalopram； there was no significant correlation of HTTLPR genotype with remission rate [LS/SS vs. LL： OR＝ 0.92，95%CI（0.77， 1.10）， P＞0.05； SS vs. LL/LS：OR＝0.73， 95%CI（0.45， 1.19）， P＞0.05] or overall incidence of ADR in patients with gene SLC6A4； but high expression of rs25531 LA was significantly associated with reduced incidence of ADR（P＜ 0.05）. CYP2C19*2/*3 allele was significantly associated with slowed metabolism， higher response rate and increased incidence of ADR. CONCLUSIONS HTTLPR LL genotype is associated with the increased response rate of citalopram/escitalopram， but no significant correlation with safety is found， while CYP2C19*2/*3 allele is significantly associated with higher response rate and reduced tolerability.
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OBJECTIVE To develop an individualized medication list for elderly patients by evidence-based pharmacy method， and to support clinical decisions on rational use of METHODS Firstly， drugs with risk genetic information were screened out by systematically reviewing evidence-based pharmacy information. Secondly， researchers investigated the included drugs in lists from different data E- sources. Drugs included in three or more data sources and drugs proposed by the expert committee were then included in the medication list. Thirdly， for the drugs included in two data sources， researchers designed questionnaires to investigate the necessity of drug-related gene testing. According to the scoring results of the expert questionnaire， drugs with higher scores were included in the list. Data sources included real-world data （list of high frequency medication in hospitals， high frequency medication for elderly outpatients and inpatients in National Health Care Claims Data， drugs related to frequent medication errors and so on） and evidence-based pharmacy evidence （the websites of Clinical Pharmacogenomics Implementation Consortium， Dutch Pharmacogenetics Working Group， Food and Drug Administration and so on）. RESULTS The study obtain 68 drugs with risk genetic information which were included in three data sources. Combined with 23 drugs proposed by the expert committee， a list containing 74 drugs was preliminarily formed after de-duplication. A total of 37 drugs included in two databases with risk genetic information were scored through the questionnaire survey to form a supplementary list of 26 drugs. This is the final composition of the list of 100 drugs developed in this study. Among them， there are 43 drugs for the central nervous system， 15 drugs for the cardiovascular system， 12 anti-tumor drugs and so on. Twelve drugs were included in six or more data sources， which mainly consisted of drugs for digestive system， all proton pump inhibitors. CONCLUSION In this study， a list of 100 commonly used drugs which require individualized medication for the elderly was developed by evidence-based pharmacy method. The drug list will be updated in time as available evidence changes， and can provide guidance for rational use of medicines for elderly patients.
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OBJECTIVE：To compare the effectiveness and safety of int ensified dose and standard dose of mycophenolic acids （MPA）for kidney transplant recipients ，and to provide evidence-based reference for clinical use of drugs. METHODS ：Retrieved from Embase ，PubMed，Cochrane library ，Clinical trials ，CNKI，Wanfang database and CBM ，randomized controlled trial （RCT） and cohort study about intensified dose and standard dose of clinical commonly used Mycophenotate mofetil （MMF） and Mycophenolate sodium enteric-coated tablet （EC-MPS）for adult kidney transplant recipients were collected during the inception to Mar. 2020. After literature screening and data extraction ，the quality of RCTs were evaluated with bias risk evaluation tool recommended by Cochrane system evaluator manual 5.0. The quality of cohort study was evaluated by NOS scale. Meta-analysis was performed by using Rev Man 5.3 software，and sensitivity analysis was conducted. RESULTS ：A total of 8 studies were included，involving 6 RCTs，2 cohort studies ，with 1 637 patients involved. Meta-analysis results showed that ，the incidence of biopsy-proven acute rejection （BPAR）[RR＝0.65，95％CI（0.48，0.89），P＝0.007] and cytomegalovirus （CMV）infection [RR ＝ 0.39，95％CI（0.17，0.91），P＝0.03] in intensified dose groupwere significantly lower than control group. Subgroup analysis by drug showed that the incidence of BPAR in MMF intensive dose group [RR ＝0.72，95％CI（0.53，0.99），P＝0.04] and EC-MPS intensive dose group [RR ＝0.19，95％ CI （0.04， 0.81），P＝0.03] was significantly lower than that in standard zhaorongsheng@bjmu.edu.cn dose group ； there was n o statistical significance in the incidence of CMV infection in MMF intensive dose group [RR ＝0.16，95％CI（0.02，1.33），P＝0.09] and EC-MPS intensive dose group [RR ＝0.51，95％CI（0.20，1.30），P＝0.16]，compared with standard dose group （P＞0.05）. There was no significant difference in the incidence of rejection，treatment failure ，graft loss ，termination of treatment ，death，overall adverse events ， infection（overall），BK virus infection ，urinary tract infection ，hematological adverse events （overall），leucopenia，anemia， thrombocytopenia，gastrointestinal adverse events （overall），nausea，vomiting or diarrhea between 2 groups（P＞0.05）. Sensitivity analysis showed that the incidence of rejection ，CMV infection and leukopenia were generally stable. CONCLUSIONS ：The efficacy and safety of early intensive dose of MPA in adult renal transplant recipients were similar to those of standard dose ，but the incidence of rejection ，CMV infection and leucopenia should be carefully interpreted.
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OBJECTIVE：To conduct reevaluation of systematic review/Meta-ana lysis on the efficacy and safety of selegiline in the treatment of Parkinson ’s disease （PD）. METHODS ：Retrieved from PubMed ，Embase，Cochrane L ibrary，CNKI，Wanfang database as well as official websites of domestic and foreign health technology assessment institutions ，based on manual retrieval and review of references ，systematic review/Meta-analysis on selegiline alone or combined with other anti-PD drugs （trial group ） versus placebo or blank control or other anti-PD drugs （control group ）were collected. The time limit was from database inception to November 2020. After literature screening and data extraction ，PRISMA statement was adopted to evaluate the quality of the included reports. AMSTAR 2 scale was used to evaluate the methodological quality ，and GRADE method was adopted to evaluate the evidence quality ，the outcome indicators of the included studies were summarised and analyzed. RESULTS ：A total of 12 systematic reviews/Meta-analysis were included ，involving 4 systematic reviews and 8 Meta-analysis；there were 31 outcome indexes in total. PRISMA scores of them ranged from 16.5 to 27.0，including 15.0 to 21.0 for 2 literatures（16.67％）and 22.0 to 27.0 for 10 literatures（83.33％）. Results of AMSTAR 2 scale showed that the methodological qualities of 2 literatures were classed as high quality ，3 as low quality and 7 as very low quality. Results of GRADE evidence quality evaluation showed that 1 evidence quality was high-level ，3 were medium-level ，5 were low-level ，21 were very low-level ，and 1 was no evaluable . The main factors leading to the degradation were bias risk （87.10％），publication bias （77.42％），inaccuracy （51.61％）and incon sistency（41.94％）. In terms of therapeutic efficacy ，compared with control group ，selegiline could improve the total score of UPDRS ，UPDRS Ⅰ score，UPDRS Ⅱ score，UPDRS Ⅲ score and Webster score in patients with Parkinson ’s disease，either monotherapy or in combination with other anti-PD drugs （P＜0.05）. In terms of safety ，there was no significant difference in the incidence of adverse events or mortality between 2 groups（P＞0.05），but the rate of withdrawal due to adverse events was higher（P＜0.05）. CONCLUSIONS ：Selegiline is effective and safe in the treatment of Parkinson ’s disease ，but current methodological quality and evidence quality of included systematic reviews /Meta-analysis are low，which requires further standardization of research methods.
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OBJECTIVE：To systematically evaluate the c orrelation of methylenetetra hydrofolate reductase （MTHFR）C677T and A 1298C gene polymorphisms with blood system adverse events induced by high-dose of methotrexate （HDMTX）. METHODS ： Retrieved from Medline ，Embase，Clinical Trials.gov ，CNKI，Wanfang database ，CBM，cohort studies about MTHFR gene polymorphism in hematological neoplasm treated by HDMTX were collected from inceptions to March 2018. After data extraction of included literatures ，quality evaluation with Newcastle Ottawa scale ，Meta-analysis was performed for adverse events of blood system induced by HDMTX in different genetic models with Rev Man 5.3 software. RESULTS ：Totally 25 cohort studies were included，23 studies of which were related to MTHFR C677T site （including 1 858 patients）and 16 studies related to MTHFR A1298C site （including 1 088 patients）. Results of Meta-analysis showed that MTHFR C677T mutation type significantly increased the risk of hematotoxicity [TT/CT vs. CC ：OR＝1.57，95％CI（1.12，2.20），P＝0.009；TT vs. CT/CC ：OR＝2.19，95％CI（1.49， 3.23），P＜0.001；T vs. C ：OR＝1.34，95％CI（1.03，1.74）， P＝0.03] and severe hematotoxicity [TT/CT vs. CC ：OR＝m 2.33，95％CI（1.43，3.81），P＜0.001]，including leukopenia [TT/CT vs. CC ：OR＝1.37，95％CI（1.02，1.82），P＝0.03]， severe leukopenia [TT/CT vs. CC ：OR＝1.63，95％CI（1.03， 010-82265810。E-mail：zhao_rongsheng@163.com 2.56），P＝0.04]，severe gra nulopenia [TT/CT vs. CC ：OR＝ ·2.26，95％CI（1.50，3.39），P＜0.001]. The mutation genotypes of MTHFR A1298C significantly decreased the risk of severe hematotoxicity [CC/AC vs. AA ：OR＝0.17，95％CI（0.04，0.76），P＝0.02]，including leukopenia [CC/AC vs. AA ：OR＝0.68， 95％CI（0.48，0.97），P＝0.03；CC vs. AC/AA ：OR＝0.28，95％CI（0.14，0.59），P＜0.001] and severe leukopenia [CC/AC vs. AA：OR＝0.43，95％CI（0.19，0.97），P＝0.04]. CONCLUSIONS ：Among patients with hematological neoplasms ，MTHFR C677T mutation may significantly increase the risk of hematotoxicity by HDMTX including the risk of leukopenia and granulopenia ；while MTHFR A1298C may reduce the risk of hematotoxicity by HDMTX ，including the risk of leukopenia.
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OBJECTIVE：To p rovide reference for related pharmacy work for developing evidence-based pharmacy information support to respond for novel coronavirus pneumonia （COVID-19） epidemic. METHODS ：The PubMed，CNKI and Wanfang database were consulted to obtain treatment progress of COVID-19，prohibited for use with lopinavir/ritonavir and adverse drug reactionas until February 12，2020；so were package insert and UpToDate at the same time. Those information were summarized and evaluated. RESULTS & CONCLUSIONS ：Totally 14 literatures introduced chemical drugs for COVID- 19，involving 7 categories， 20 kinds of chemical drugs as antiviral drugs （interferon α/interferon α-2 β ， lopinavir/litonavir， etc.）， immunomodulatory agents （such as glucocorticoid ，gamma globulin ），antimalarial drugs （such as chloroquine phosphate ）. The existing evidence of drug treatment mainly comes from in vitro cell test or currently progressing RCT ，with low-level evidence and recommendation intensity （Oxford evidence level is level 5，recommendation intensity is level D ）. For lopinavir/ritonavir that recommended in the diagnosis and treatment recommendations for COVID- 19 published by the National Health Commission ，it is a CYP3A inhibitor ，which resulted in increased plasma concentrations of some medications such as antiarrhythmic drugs ，antitumor targeted drugs and antibacterial drugs ，and should not be used in combination with drugs such as afzosin ，ivabradine，amiodarone， etc. Its common adverse reactions mainly involved igestive system （diarrhea，taste disorders ，vomiting，etc.），respiratory system （upper respiratory tract infection ），endocrine and metabolic system （hypercholesterolemia，etc.），skin and its appendents （skin rash），which should be monitored clinically.
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OBJECTIVE：To provid e reference for pharmaceutical workers to better understand Novel Coronavirus Infection ： Expert Consensus on Guidance and Prevention Strategies for Hospital Pharmacists and the Pharmacy Workforce （hereinafter referred to as “expert consensus ”），and to apply and practice in specific work ，so as to give full play to the role of pharmacists to help fight the epidemic.METHODS ：The background of the formulation and revision of the expert consensus were introduced ，and its main contents and viewpoints were interpreted. RESULTS & CONCLUSIONS ：The text of expert consensus is divided into 8 parts，mainly including disease diagnosis and treatment [SARS-CoV- 2 infection related background ，clinical manifestations and diagnosis， treatment]，hospital pharmacy （prevention and control strategy ，work guidance ），drug and facility support management（key drug/facility/equipment support ，management and use of the drug in special circumstances ），information sources and related resources ，etc.，which comprehensively and detailedly provide information ，guidance and strategies for coronavirus SARS-CoV-2 infection prevention and control to play the role of pharmacists in hospital pharmacy well ，do well in the protection of staff in different pharmaceutical posts ，drug security work in response to epidemic situation ，and develop pharmaceutical care. So far，the understanding of SARS-CoV- 2 in the pharmaceutical industry is relatively limited. Based on the accumulated experience and progress in epidemic prevention and control ，the expert consensus will be updated and improved continuously ，so as to provide guidance and help for hospital pharmaceutical personnel.
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OBJECTIVE： To systematically evaluate the effects of MTHFR， RFC1 and MDR1 gene polymorphisms on high- dose methotrexate-induced ADR in osteosarcoma patients， and to provide evidence-based reference for individual medication of high-dose of methotrexate. METHODS： Retrieved from Medline， Embase， clinical trials.gov， CNKI， Wanfang database and CBM， cohort studies about the association of MTHFR C677T/A1298C， RFC1 G80A， MDR1 C3435T gene polymorphisms with high-dose methotrexate-induced ADR were collected. After data extraction of clinical studies met inclusion criteria， and quality evaluation with the Newcastle-Ottawa Scale， Meta-analysis and descriptive analysis were performed for outcome indexes as the incidence of high-dose methotrexate-induced ADR （hematotoxicity and myelosuppression， hepatotoxicity， nephrotoxicity， oral mucositis， digestive tract toxicity and overall adverse events） with Rev Man 5.3 and Microsoft Excel 2016 software. RESULTS： Totally 8 cohort studies involving 608 patients were included； 6， 5， 4 and 2 studies reported outcome indexes related to MTHFR C677T/A1298C， RFC1 G80A and MDR1 C3435T gene polymorphisms respectively. Meta-analysis and descriptive analysis showed that MTHFR C677T gene polymorphism was significantly associated with the risk of G3-4 renal toxicity [TT/CT vs. CC： OR＝12.35， 95％CI＝（3.28，46.42）， P＜0.001]， G3-4 oral mucositis [T vs. C： OR＝2.04， 95％CI＝（1.06，3.93）， P＝0.03]， oral mucositis [（TT vs. CT/CC： OR＝2.27， 95％CI＝（1.20，4.27）， P＝0.01] and renal toxicity （P＜0.05）； MTHFR A1298C gene polymorphism was associated with G3-4 hepatotoxicity， G3-4 nephrotoxicity and G3-4 oral mucositis， without statistical significance （P＞0.05）. There was no significant correlation between RFC1 G80A polymorphism and hemotoxicity， hepatotoxicity， nephrotoxicity and digestive tract toxicity （P＞0.05）. MDR1 C3435T polymorphism was significantly correlated with oral mucositis （P＜0.05）， but not with hematotoxicity and hepatotoxicity （P＞0.05）. CONCLUSIONS： MTHFR C677T mutation can increase the risk of high-dose methotrexate-induced ADR. There is no significant association between MTHFR A1298C polymorphism and high-dose methotrexate-induced ADR. There are few studies on RFC1 G80A or MDR1 C3435T polymorphism and high-dose methotrexate-induced ADR， and their association is unclear.
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Objective:To assess the effect of B group vitamins on cerebrovascular diseases, and also to evaluate the relationship between B group vitamins and homocysteine(Hcy). Methods:Using the words homocysteine,folic acid,folate,cerebrovascular dis-ease,B group vitamins and randomized controlled trial as the keywords,PubMed,the Cochrane library,WanFang Database,VIP and CNKI were searched. The randomized controlled trials about preventive effect of folic acid,vitamin B12or vitamin B6on cerebrovascular disease occurring published between 1998 and July 2016 were searched by manually retrieving relevant journals. Two reviewers inde-pendently screened the trials,extracted the data and evaluated the quality of included trials. The Cochrane Collaboration's RevMan 5.3 software was used for the statistical analysis. Results:Twelve trials involving 36 053 patients were included. The results of meta-analysis showed that B group vitamins could lower the risk of stroke(RR=0.90,95% CI:0.82-0.99,P=0.02). The sensitivity a-nalysis conducted after the exclusion of low-quality trials did not change the overall results, and B group vitamins could lower plasma Hcy concentration (MD= -3.40,95% CI:-4.21--2.59, P<0.000 01). Conclusion: B group vitamins can lower plasma Hcy concentration,and lower the risk of stroke. B group vitamins supplementation should be recommended for the secondary prevention of stroke. The results of this study still need more reasonable design combined with strict implementation of larger samples of randomized double-blind controlled trials.