The Study Of Evaluation For Adverse Drug Reactions Of Traditional Chinese Medicine Injections For Hand-foot-mouth Disease Treament Based On The Real World Data

ObjectiveTo explore adverse drug reactions(ADR)type and main drugs in the treatment of hand-foot-mouth disease(HFMD)caused by traditional Chinese medicine injection and then to figure out some key Drug ADR characteristics,ADR related organs,factors influencing ADR state.Besides,to build the of ADR state prediction model and observation model,in order to fill the blank of traditional Chinese medicine injection adverse reaction characteristics which are not clear,so as to provide reference for clinical rational use of drugs and security work.Methods1.The type and drug composition of ADR for HFMD treated by traditional Chinese medicine injection:(1)Data retrieval and cleaning.Research based on "report on the adverse drug reactions/events" of Guangdong ADR monitering Center "pan-pearl river delta ADR network management platform" about "hand,foot and mouth disease case.Classification and the severity of ADR and its causality assessment are all based on the "regulations on the administration of adverse drug reaction report and monitoring" from the ministry of health released in May 2011,and ADR related system classification is based on World Health Organization Adverse Reaction Terms from the world health organization(WHO-ART)standard.(2)Pareto diagram analysis.Use SPSS 16.0 statistical software package for descriptive analysis of ADR types and drug varieties,and using Excel software of office implements the pareto chart analysis in order to find out the auxiliary of TCM injections in HFMD treatment guidelines recommend medication and figure out the hand,foot and mouth disease treatment to ADRs of TCM injections for further study.2.Based on data mining methods with the real world big data,to operate ADR evaluation research about HFMD ADRs caused by traditional Chinese medicine injection:(1)Data retrieval,extraction,audit and cleaning: to batch data assimilation on drug concentration in the composition of unit conversion according to Chinese Food and Drug Administration(CFDA)record information.Clean and classify the terms of "adverse reactions/events name","the original disease","the combination drugs",and ADR evaluation result variables.(2)Data analysis and mining based on R language: using R language(https://www.r-project.org)to install R packages such as plyr,dplyr,MASS,fifer,etc.,to carry out descriptive analysis and figure out description of drug ADR population characters and drug use characteristics.And install and load Matrix,arules,grid,arules,arules Viz,RColor Brewer R package for unsupervised based on association rules Apriori algorithm analysis involving multiple organs or systems of ADR characteristic symptoms of rule mining and network diagram.The random Forest R package was installed to carry out to find important influence factor on the ADR state and the extraction and sequencing of the key accumulative organs based on Mean Decresed Gini(MDG).(3)Data analysis and mining based on weka-3-8: with weka-3-8(http://weka.wikispaces.com)set the Zero R as a baseline control level,then built the decision tree model based on C4.5 algorithm and the improved J48 algorithm.3.Contrast ADR reports of spontaneous reporting about the real world application status at domestic and abroad,through the platform of ADR monitoring center of Gguangdong province and international platform resources query,to explore the deficiency of active monitoring of ADR in our country and statements.Results1.The traditional Chinese medicine injections induced ADRs in the treatment of HFMD include Yanhuning injection(20.51%),Xiyanping injection(20.23%),Reduning injection(18.20%),Shuang Huang Lian injection(15.10%)as the main factors.Drugs which caused serious ADR includes,Yanhuning injection(37.59%),Xiyanping injection(21.80%),Reduning injection(17.29%)as the main factors,Zedoary oil injection(6.02%),Tanreqing injection(5.26%,same as Xingnaojing injection)as the secondary factor.Consequently Yanhuning injection,Xiyanping injection and Reduning injection are included in the data mining research of the real world data 2.(1)Yanhuning injection,Yanhuning injection,Reduning Injection include cases of ADRs evaluation report of 26158 cases,7843 cases,8342 cases respectively.According to the result of ADR report,the main composition of population age for children is under 5 years of age,while gender composition mostly is men without significant differences.The overall new severity ratio of all ADR reports of Yanhuning injection,Xiyanping injection,and Reduning injection were: 18.07%,25.54%,22.99%,and there was no statistical difference(p>0.05),while the influence rates of the disease were 16.74%,2.19%,14.29%,and the chi-square test was p<0.01,and the comparison showed that the influence rate of Xiyanping was significantly lower than that of the other two drugs(p<0.01).The cure rate was 60.71%,56.55% and 56.66% respectively without statistical difference(p>0.05).(2)In the overall case mining of Yanhuning injection,one association rule whose lift>1.5 was made,"site damage = > damage of skin and its accessories",clinical performance includes site redness,concurrently with itchy skin,rash,or wheal.From Xiyanping,two association rules whose lift> 1.5 were improved,while they includes "damage of cardiovascular system and the blood coagulation disorder = > skin and its accessories damage ",indicating clinical performance for hot flashes,high fever,chills,limbs cold concurrently with skin rashes,itching,hives and another rule is "Site damage => skin and its accessory damage",indicating the clinical manifestation of infusion site redness or pruritus,injection site pain or hard knot,with macular rash,rash,pruritus.As for Reduning injection,three association rules whose lift >1.5 were obtained: the first one is "visual impairment => skin and its accessory damage",with the clinical manifestations of eyelid edema,eyelid congestion and rash,pruritus."Systemic damage,visual impairment => skin and its accessory damage" is clinically manifested as eye pain,watery eyes and periorbital edema,high fever,lip swelling and rash,pruritus;"Vascular system damage and blood coagulation disorder => skin and its accessory damage",clinical manifestations are hot flashes,phlebitis and herpes,itching,rash.(3)Based on random forest law of the MDG,it is concluded that from Yanhuning injection,Xiyanping injection,Reduning injection the importance of the influence factors of the occurrence of new or severe ADR are respectively: age,weight,single drug dosage,nation,solvent;Age,weight,year of batch number,single dosage of medicine,number of days of medication;Age,weight,batch number,single dosage of medicine,number of days of medication.The importance of the organ system is respectively: skin and its accessory damage,systemic damage,respiratory system damage;Skin and its accessory damage,systemic damage,nervous system damage;Systemic damage,skin and its accessories damage,respiratory damage.(4)Xiyanping ADR system involved observation decision tree and Reduning ADR system involved observation decision tree improved ROC curve with AUC value >0.7,obtaining a good prediction effect.Conclusion1.When using traditional Chinese medicine injection treatment to cure HFMD,attention to the occurrence of skin and its accessories damage should be especially paid,the drug monitoring of Yanhuning injection,Xiyanping injection,Reduning injection should be strengthened,as well as the Zedoary oil injection and Xingnaojing injection,which attention should especially paid during the ADR processing.2.Yanhuning,Xiyanping,Reduning affected organs characteristics of drug and ADR population characteristics are significantly different,according to the tendency of performance system attention for drug safety monitoring should be paid,and serious important risk factors should be noticed.3.Evaluation scheme model based on the real world big data of traditional Chinese medicine injection ADR assessment is initially set up,comprehensively including the population characteristics,the characteristics of ADR,single system damage characteristics and multiple system damage associated,the influence factors,the results of the ADRs,the forecast model and observation model.Besides,the R language use scenarios in the evaluation of ADR area was made,which is suitable for whole index Chinese medicine injection ADR evaluation and information extraction of big data.