Validation of a model-based virtual trials method for tight glycemic control in intensive care 英文参考文献.docVIP

Validation of a model-based virtual trials method for tight glycemic control in intensive care 英文参考文献.doc

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Validation of a model-based virtual trials method for tight glycemic control in intensive care 英文参考文献

Chaseetal.BioMedicalEngineeringOnLine2010,9:84 /content/9/1/84 RESEARCH OpenAccess Validationofamodel-basedvirtualtrialsmethod fortightglycemiccontrolinintensivecare JGeoffreyChase1*,FatanahSuhaimi1,SophiePenning2,Jean-CharlesPreiser3,AaronJLeCompte1,JessicaLin4, ChristopherGPretty1,GeoffreyMShaw4,5,KatherineTMoorhead2,ThomasDesaive2* *Correspondence:geoff. Abstract chase@canterbury.ac.nz; tdesaive@ulg.ac.be Background:In-silicovirtualpatientsandtrialsoffersignificantadvantagesincost, timeandsafetyfordesigningeffectivetightglycemiccontrol(TGC)protocols. 1DeptofMechanicalEng,Centre forBio-Engineering,Universityof Canterbury,Christchurch,Private Bag4800,8054,NewZealand 2CardiovascularResearchCentre, InstitutedePhysique,Universitede Liege,InstituteofPhysics,Alléedu 6Ao?t,17(BatB5),B4000Liege, Liege,Belgium However,nosuchmethodhasfullyvalidatedtheindependenceofvirtualpatients (orresultingclinicaltrialpredictions)fromthedatausedtocreatethem.Thisstudy usesmatchedcohortsfromaTGCclinicaltrialtovalidatevirtualpatientsandin-silico virtualtrialmodelsandmethods. Methods:Datafroma211patientsubsetoftheGlucontroltrialinLiege,Belgium. Glucontrol-A(N=142)targeted4.4-6.1mmol/LandGlucontrol-B(N=69)targeted 7.8-10.0mmol/L.CohortswerematchedbyAPACHEIIscore,initialBG,age,weight, BMIandsex(p0.25).Virtualpatientsarecreatedbyfittingaclinicallyvalidated modeltoclinicaldata,yieldingtimevaryinginsulinsensitivityprofiles(SI(t))that drivesin-silicopatients. Modelfitandintra-patient(forward)predictionerrorsareusedtovalidateindividual in-silicovirtualpatients.Self-validation(testsAprotocolonGroup-Avirtualpatients; andBprotocolonBvirtualpatients)andcross-validation(testsAprotocolonGroup- Bvirtualpatients;andBprotocolonAvirtualpatients)areusedincomparisonto clinicaldatatoassessabilitytopredictclinicaltrialresults. Results:Modelfiterrorsweresmall(0.25%)forallpatients,indicatingmodelfitness. Medianforwardpredictionerrorswere:4.3,2.8and3.5%forGroup-A,Group-Band Overall(A+B),indicatingindividualvirtua

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