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Evidence-based Practice Guideline of Medication Therapy of High-dose Methotrexate in China was published in the British Journal of Clinical Pharmacology in February 2022. The guideline followed the latest definition of clinical practice guideline and the methodology specification for the guideline development of WHO. The Grading of Recommendations Assessment ， Development，and Evaluation （GRADE）approach was applied to rate the quality of evidence and determine the strength of recommendations. Finally ，this guideline presents 28 recommendations covering the whole process of clinical medication of high-dose methotrexate ，involving evaluation prior to administration （liver and renal function ，pleural effusion and ascites ， comedication，genetic testing ），pre-treatment and routine dosing regimen （pretreatment of hydration and alkalization ，urine alkalization，routine dosing regimen ），therapeutic drug monitoring （necessity，method，timing，target concentration ），leucovorin rescue（rescue timing ，rescue regimen ，rescue dose optimization ），and management of toxicities （liver and kidney function monitoring，supportive treatment ，blood purification treatment ）. This article aims to summarize and interpret the recommendations of this guideline ，so as to promote the better promotion and implementation of this guideline and provide comprehensive technical support and suggestions for whole-course individualized administration of high-dose methotrexate in China.
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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 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 systematically evaluate the efficacy and safety for different infusion schemes of large-dose （＞500 mg/m2） of methotrexate in the treatment of osteosarcoma， and to provide evidence-based reference for clinical treatment. METHODS： Retrieved from Medline， Embase， clinicaltrials.gov， CJFD， Wanfang database and CBM database， observational studies and randomized/non-randomized controlled trials about therapeutic efficacy and safety for different infusion schemes （different doses and infusion time） of large-dose of methotrexate in the treatment of osteosarcoma were included during the establishment of the database to Mar. 2018. After data extraction and quality evaluation with methodological evaluation index of the Newcastle-Ottawa scale， Cochrane 5.1.0 bias risk evaluation tool and non-randomized controlled trials， Meta-analysis or descriptive analysis for blood drug concentration （c）， related toxicity （e.g. incidence of hepatotoxicity， incidence of hemotoxicity） were performed by using Rev Man 5.3 software. RESULTS： Totally 5 studies were included， involving 310 cases. Results of Meta-analyses indicated c0 h [MD＝－240.11， 95％CI（－271.47， －208.75）， P＜0.001]， c24 h [MD＝－0.09， 95％CI （－0.11， 0.08）， P＜0.001]， c48 h [MD＝－0.07， 95％CI （－0.10， －0.05）， P＜0.001]， c72 h [MD＝－0.05， 95％CI （－0.06， －0.03）， P＜0.001] and the incidence of liver toxicity [OR＝0.26， 95％CI （0.10， 0.67）， P＜0.005] in 8 g/m2 group were significantly lower than 10 g/m2 group. Results of descriptive analysis showed that when both groups were given 8 g/m2， c24 h of patients with 2 and 4 h infusion time was significantly lower than that of patients with 6 h infusion time. The incidence of leukopenia and thrombo- cytopenia in 8 g/m2 group was significantly lower than 10 g/m2 group. CONCLUSIONS： In the treatment of osteosarcoma with high-dose of methotrexate， appropriate dosage reduction （e.g. 8 g/m2） and appropriate prolongation of infusion time （e.g. 6 h） may lead to a better efficacy and safety.
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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.