2023
Effectiveness of a Quality Improvement Intervention on Reperfusion Treatment for Patients With Acute Ischemic Stroke
Wang C, Gu H, Zong L, Zhang X, Zhou Q, Jiang Y, Li H, Meng X, Yang X, Wang M, Huo X, Wangqin R, Bei Y, Qi X, Liu X, Hu S, Wang Z, Zhao X, Wang Y, Liu L, Ma X, Morgan L, Xian Y, Schwamm L, Wang Y, Li Z, Yang Q, Chen G, Ma Q, Li X, Chen J, Zhao X, Wang H, Niu X, Xu J, Zhao L, Wang Z, Huang D, Jin X, Chen S, Li J, Yu J, Liu P, Li G, Hao Y, Yang G, Huang X, Zhou C, Yang J, Gu J, Sun P, Guo Z, Ma G, Chen G, Tang M, Wang N, Chen L, Li J, Li A, Li S, Cao M, Guo J, Ren Y, Li T, Zhang L, Xie Z, Dong J, Kong X, Liang H, Zhang Y. Effectiveness of a Quality Improvement Intervention on Reperfusion Treatment for Patients With Acute Ischemic Stroke. JAMA Network Open 2023, 6: e2316465. PMID: 37266940, PMCID: PMC10238948, DOI: 10.1001/jamanetworkopen.2023.16465.Peer-Reviewed Original ResearchConceptsAcute ischemic strokeQuality improvement interventionsTargeted quality improvement interventionsReperfusion therapy ratesProportion of patientsIschemic strokeEligible patientsStepped-wedge clusterSymptom onsetReperfusion therapyEndovascular thrombectomyImprovement interventionsTherapy ratesUsual careSecondary outcomesPrimary outcomeSecondary hospitalsClinical trialsIntravenous recombinant tissue plasminogen activatorModified Rankin Scale scoreRecombinant tissue plasminogen activatorRankin Scale scoreTissue plasminogen activatorEVT rateHospital mortality
2022
Race-Ethnic Disparities in Rates of Declination of Thrombolysis for Stroke
Mendelson S, Zhang S, Matsouaka R, Xian Y, Shah S, Lytle B, Solomon N, Schwamm L, Smith E, Saver J, Fonarow G, Holl J, Prabhakaran S. Race-Ethnic Disparities in Rates of Declination of Thrombolysis for Stroke. Neurology 2022, 98: e1596-e1604. PMID: 35228335, PMCID: PMC9052571, DOI: 10.1212/wnl.0000000000200138.Peer-Reviewed Original ResearchConceptsTissue plasminogen activatorNon-Hispanic black patientsTPA-eligible patientsRace/ethnicityBlack patientsNon-Hispanic black race/ethnicityNon-Hispanic white patientsBlack race/ethnicityAsian race/ethnicityGuidelines-Stroke registryPrimary stroke centerSingle-center studyMultivariable logistic regressionRace-ethnic disparitiesNon-Hispanic whitesEligible patientsHospital factorsNationwide registryPatient demographicsStroke centersSymptom onsetWhite patientsMultivariable analysisStroke careAsian patients
2021
Exploring the Unmet Need in Acute Ischemic Stroke Patients Not Treated With Intravenous Alteplase: The Get With The Guidelines‐Stroke Registry
Mac Grory B, Xian Y, Solomon N, Matsouaka R, Decker‐Palmer M, Fonarow G, Smith E, Schwamm L. Exploring the Unmet Need in Acute Ischemic Stroke Patients Not Treated With Intravenous Alteplase: The Get With The Guidelines‐Stroke Registry. Stroke Vascular And Interventional Neurology 2021, 2 DOI: 10.1161/svin.121.000226.Peer-Reviewed Original ResearchGuidelines-Stroke registryAcute ischemic strokeIschemic strokePatient populationCommon reasonUnmet needAcute ischemic stroke patientsIntravenous tissue plasminogen activatorAcute ischemic stroke careGuidelines-Stroke hospitalsIschemic stroke patientsIschemic stroke careLong-term outcomesTissue plasminogen activatorAlteplase deliveryHospital mortalityIntravenous alteplaseClinical characteristicsConclusions PatientsReadmission ratesEarly administrationPostdischarge costsStroke careStroke patientsFunctional outcomeClinical Characteristics, Management, and In-Hospital Outcomes in Patients With Stroke or Transient Ischemic Attack in China
Gu H, Yang X, Wang C, Zhao X, Wang Y, Liu L, Meng X, Jiang Y, Li H, Liu C, Wangqin R, Fonarow G, Schwamm L, Xian Y, Li Z, Wang Y. Clinical Characteristics, Management, and In-Hospital Outcomes in Patients With Stroke or Transient Ischemic Attack in China. JAMA Network Open 2021, 4: e2120745. PMID: 34387677, PMCID: PMC8363916, DOI: 10.1001/jamanetworkopen.2021.20745.Peer-Reviewed Original ResearchConceptsTransient ischemic attackChinese Stroke Center AllianceMajor adverse cardiovascular eventsHospital clinical outcomesQuality improvement studyIschemic strokeIntracerebral hemorrhageIschemic attackClinical characteristicsClinical outcomesPoor outcomeIntravenous recombinant tissue plasminogen activatorTemporal improvementRecombinant tissue plasminogen activatorAdverse cardiovascular eventsIn-Hospital OutcomesUse of anticoagulantsComposite scoreImprovement studyTissue plasminogen activatorMean composite scoreHealth care systemHospital complicationsTIA admissionsTIA care
2020
Association Between Thrombolytic Door-to-Needle Time and 1-Year Mortality and Readmission in Patients With Acute Ischemic Stroke
Man S, Xian Y, Holmes D, Matsouaka R, Saver J, Smith E, Bhatt D, Schwamm L, Fonarow G. Association Between Thrombolytic Door-to-Needle Time and 1-Year Mortality and Readmission in Patients With Acute Ischemic Stroke. JAMA 2020, 323: 2170-2184. PMID: 32484532, PMCID: PMC7267850, DOI: 10.1001/jama.2020.5697.Peer-Reviewed Original ResearchConceptsIntravenous tissue plasminogen activatorAcute ischemic strokeTissue plasminogen activatorCause mortalityNeedle timeCause readmissionIschemic strokeLong-term outcomesShorter doorBetter long-term outcomesImproved long-term outcomesPlasminogen activatorRetrospective cohort studyGood functional outcomeGuidelines-StrokeCohort studyHospital arrivalHospital dischargeMedian doorEarly administrationMedian agePrimary outcomeThrombolytic therapyFunctional outcomeReadmissionAcute ischemic stroke: improving access to intravenous tissue plasminogen activator
Turner A, Schwamm L, Etherton M. Acute ischemic stroke: improving access to intravenous tissue plasminogen activator. Expert Review Of Cardiovascular Therapy 2020, 18: 277-287. PMID: 32323590, DOI: 10.1080/14779072.2020.1759422.Peer-Reviewed Original ResearchConceptsAcute ischemic strokeIschemic stroke patientsIschemic strokeStroke patientsTreatment windowAcute ischemic stroke patientsIntravenous tissue plasminogen activatorTreatment ratesUnknown symptom onsetAcute stroke careTissue plasminogen activatorQuality improvement initiativesHealth care resourcesUnited States FoodStroke outcomeSymptom onsetStroke careStroke specialistsStroke systemsTelestroke networkDrug AdministrationAlteplasePatientsPlasminogen activatorStates Food
2019
Thrombolytic therapy in older acute ischemic stroke patients with gastrointestinal malignancy or recent bleeding
Inohara T, Liang L, Kosinski A, Smith E, Schwamm L, Hernandez A, Bhatt D, Fonarow G, Peterson E, Xian Y. Thrombolytic therapy in older acute ischemic stroke patients with gastrointestinal malignancy or recent bleeding. European Stroke Journal 2019, 5: 47-55. PMID: 32232169, PMCID: PMC7092738, DOI: 10.1177/2396987319871784.Peer-Reviewed Original ResearchRecombinant tissue plasminogen activatorRecent gastrointestinal bleedingAcute ischemic strokeGastrointestinal malignanciesIschemic strokeGastrointestinal bleedingHospital mortalityIntravenous recombinant tissue plasminogen activatorOlder acute ischemic stroke patientsAcute ischemic stroke patientsRtPA-treated patientsIschemic stroke patientsTissue plasminogen activatorOutcomes of interestGuidelines-StrokeIndex strokeRecent bleedingSevere strokeObservational cohortClinical outcomesStroke patientsThrombolytic therapyBleedingSystemic hemorrhagePatientsIntravenous Tissue Plasminogen Activator in Stroke Mimics
Ali-Ahmed F, Federspiel J, Liang L, Xu H, Sevilis T, Hernandez A, Kosinski A, Prvu Bettger J, Smith E, Bhatt D, Schwamm L, Fonarow G, Peterson E, Xian Y. Intravenous Tissue Plasminogen Activator in Stroke Mimics. Circulation Cardiovascular Quality And Outcomes 2019, 12: e005609. PMID: 31412730, PMCID: PMC6699639, DOI: 10.1161/circoutcomes.119.005609.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntravenousAdultAgedAged, 80 and overBrain IschemiaDiagnosis, DifferentialFemaleFibrinolytic AgentsHumansIntracranial HemorrhagesMaleMiddle AgedPredictive Value of TestsRegistriesRisk AssessmentRisk FactorsStrokeThrombolytic TherapyTissue Plasminogen ActivatorTreatment OutcomeUnited StatesUnnecessary ProceduresConceptsTransient ischemic attackStroke mimicsIschemic strokeIschemic attackPrior stroke/transient ischemic attackStroke/transient ischemic attackIntravenous tissue plasminogen activatorGuidelines-Stroke registrySymptomatic intracranial hemorrhageCardiovascular risk factorsHealth Stroke ScaleHospital mortality rateAcute ischemic strokeStroke-like symptomsTissue plasminogen activatorUse of tPANonstroke diagnosisThrombolysis safetyIntravenous tPAStroke ScaleComplication rateIntracranial hemorrhagePresumed strokeRisk factorsFunctional disordersThrombolysis in young adults with stroke: Findings from Get With The Guidelines-Stroke.
Dodds J, Xian Y, Sheng S, Fonarow G, Bhatt D, Matsouaka R, Schwamm L, Peterson E, Smith E. Thrombolysis in young adults with stroke: Findings from Get With The Guidelines-Stroke. Neurology 2019, 92: e2784-e2792. PMID: 31092622, DOI: 10.1212/wnl.0000000000007653.Peer-Reviewed Original ResearchConceptsAcute ischemic strokeTissue plasminogen activatorIschemic strokeOlder patientsYounger patientsYears of ageSymptomatic intracranial hemorrhage rateYoung adultsGuidelines-Stroke registryIntracranial hemorrhage rateGuidelines-StrokeHospital mortalityHospital arrivalHemorrhage rateIntracranial hemorrhageMultivariable modelPatientsBetter outcomesStrokePlasminogen activatorTPA treatmentTreatmentAdultsAgeOutcomes
2018
Participation in Get With the Guidelines–Stroke and Its Association With Quality of Care for Stroke
Howard G, Schwamm LH, Donnelly JP, Howard VJ, Jasne A, Smith EE, Rhodes JD, Kissela BM, Fonarow GC, Kleindorfer DO, Albright KC. Participation in Get With the Guidelines–Stroke and Its Association With Quality of Care for Stroke. JAMA Neurology 2018, 75: 1331-1337. PMID: 30083763, PMCID: PMC6248106, DOI: 10.1001/jamaneurol.2018.2101.Peer-Reviewed Original ResearchConceptsTissue plasminogen activatorIschemic strokeQuality of careGuidelines-StrokeGWTG-StrokeMean ageNonparticipating hospitalsCare measuresRisk factorsPopulation-based cohort studyPlasminogen activatorLipid profile assessmentParticipants 45 yearsStroke risk factorsQuality Improvement ProgramEvidence-based interventionsExercise counselingNeurologist evaluationAntithrombotic therapyCohort studyAntithrombotic useStroke careMAIN OUTCOMELipid evaluationHospitalQuality of Care and Outcomes for Patients With Stroke in the United States Admitted During the International Stroke Conference
Messé S, Mullen M, Cox M, Fonarow G, Smith E, Saver J, Reeves M, Bhatt D, Matsouaka R, Schwamm L. Quality of Care and Outcomes for Patients With Stroke in the United States Admitted During the International Stroke Conference. Journal Of The American Heart Association 2018, 7: e009842. PMID: 30376750, PMCID: PMC6404171, DOI: 10.1161/jaha.118.009842.Peer-Reviewed Original ResearchConceptsIntravenous tissue plasminogen activatorTissue plasminogen activatorAcute ischemic strokeInternational Stroke ConferencePlasminogen activatorWorse outcomesGuideline-adherent careGuidelines-Stroke hospitalsRetrospective cohort studyHours of onsetMinutes of arrivalExperience worse outcomesQuality of careSame quality careAverage weekly numberGuidelines-StrokeAcute strokeBackground PatientsCohort studyConclusions PatientsIschemic strokeClinical outcomesMean ageStroke cliniciansHospital characteristicsIschemic Stroke Transfer Patterns in the Northeast United States
Zachrison K, Onnela J, Hernandez A, Reeves M, Camargo C, Cox M, Matsouaka R, Metlay J, Goldstein J, Schwamm L. Ischemic Stroke Transfer Patterns in the Northeast United States. Journal Of Stroke And Cerebrovascular Diseases 2018, 28: 295-304. PMID: 30389376, DOI: 10.1016/j.jstrokecerebrovasdis.2018.09.048.Peer-Reviewed Original ResearchConceptsGuidelines-Stroke registryRegional stroke systemIschemic stroke patientsHospital connectionsTissue plasminogen activatorSevere strokeMore patientsStroke patientsIS patientsReceiving HospitalPatient dischargeStroke systemsPatient transferPatientsHospitalNortheast hospitalsMost hospitalsPlasminogen activatorCareUnited StatesFurther characterizationAdmissionRegistryStroke
2017
Recrudescence of Deficits After Stroke: Clinical and Imaging Phenotype, Triggers, and Risk Factors
Topcuoglu M, Saka E, Silverman S, Schwamm L, Singhal A. Recrudescence of Deficits After Stroke: Clinical and Imaging Phenotype, Triggers, and Risk Factors. JAMA Neurology 2017, 74: 1048-1055. PMID: 28783808, PMCID: PMC5710180, DOI: 10.1001/jamaneurol.2017.1668.Peer-Reviewed Original ResearchConceptsTransient ischemic attackRisk factorsIschemic attackChronic strokeMean ageDiagnostic criteriaPSR groupHealth Stroke Scale scoreIntravenous tissue plasminogen activatorMiddle cerebral artery territoryResearch Patient Data RepositoryCrossover cohort studyHypertensive brain hemorrhagePatients' mean ageStroke Scale scoreFocal neurologic deficitsSmall vessel diseaseCase-control studyPreliminary diagnostic criteriaTissue plasminogen activatorStroke-related deficitsMagnetic resonance imagingWhite matter tractsDiffusion-weighted imagingPatient data repositoryUse of Intravenous Recombinant Tissue Plasminogen Activator in Patients With Acute Ischemic Stroke Who Take Non–Vitamin K Antagonist Oral Anticoagulants Before Stroke
Xian Y, Federspiel J, Hernandez A, Laskowitz D, Schwamm L, Bhatt D, Smith E, Fonarow G, Peterson E. Use of Intravenous Recombinant Tissue Plasminogen Activator in Patients With Acute Ischemic Stroke Who Take Non–Vitamin K Antagonist Oral Anticoagulants Before Stroke. Circulation 2017, 135: 1024-1035. PMID: 28119380, DOI: 10.1161/circulationaha.116.023940.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntravenousAgedAged, 80 and overAnticoagulantsDabigatranFemaleFibrinolytic AgentsHemorrhageHospital MortalityHumansInternational Normalized RatioMalePyrazolesPyridonesRecombinant ProteinsRegistriesRetrospective StudiesRisk FactorsRivaroxabanStrokeTime FactorsTissue Plasminogen ActivatorTreatment OutcomeWarfarinConceptsIntravenous rt-PASymptomatic intracranial hemorrhageIschemic strokeRt-PAIntracranial hemorrhageOdds ratioNon-Vitamin K Antagonist Oral AnticoagulantsIntravenous recombinant tissue plasminogen activatorK Antagonist Oral AnticoagulantsRecombinant tissue plasminogen activatorGuidelines-Stroke registrySerious systemic hemorrhageAcute ischemic strokeAdjusted odds ratioAmerican Heart AssociationTissue plasminogen activatorOutcomes of useHospital mortalityRegistry hospitalsOral anticoagulantsSevere strokeAdverse eventsProhibitive riskRankin ScaleThrombolytic therapy
2016
Treatment With Tissue Plasminogen Activator in the Golden Hour and the Shape of the 4.5-Hour Time-Benefit Curve in the National United States Get With The Guidelines-Stroke Population
Kim J, Fonarow G, Smith E, Reeves M, Navalkele D, Grotta J, Grau-Sepulveda M, Hernandez A, Peterson E, Schwamm L, Saver J. Treatment With Tissue Plasminogen Activator in the Golden Hour and the Shape of the 4.5-Hour Time-Benefit Curve in the National United States Get With The Guidelines-Stroke Population. Circulation 2016, 135: 128-139. PMID: 27815374, DOI: 10.1161/circulationaha.116.023336.Peer-Reviewed Original ResearchConceptsAcute ischemic strokeTissue plasminogen activatorIschemic strokeHospital mortalityIndependent ambulationPlasminogen activatorTissue plasminogen activator-treated patientsIntravenous tissue plasminogen activatorTissue plasminogen activator treatmentIschemic stroke outcomeHours of onsetOdds of dischargePlasminogen activator treatmentMinutes of onsetNational United StatesHemorrhagic complicationsStroke outcomeMedian onsetThrombolytic therapyStroke systemsBetter outcomesPatientsActivator treatmentGolden hourTreatment timeWhy are acute ischemic stroke patients not receiving IV tPA?
Messé S, Khatri P, Reeves M, Smith E, Saver J, Bhatt D, Grau-Sepulveda M, Cox M, Peterson E, Fonarow G, Schwamm L. Why are acute ischemic stroke patients not receiving IV tPA? Neurology 2016, 87: 1565-1574. PMID: 27629092, PMCID: PMC5067546, DOI: 10.1212/wnl.0000000000003198.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntravenousAgedAged, 80 and overBrain IschemiaDatasets as TopicFemaleFibrinolytic AgentsHealthcare DisparitiesHumansLogistic ModelsMaleMultivariate AnalysisRegistriesRetrospective StudiesSeverity of Illness IndexStrokeThrombolytic TherapyTissue Plasminogen ActivatorUnited StatesConceptsAcute ischemic strokeTissue plasminogen activatorHours of onsetEligible patientsAcute ischemic stroke patientsNIH Stroke Scale scoreStroke center certificationRetrospective cohort studyStroke Scale scoreIschemic stroke patientsEarlier calendar yearsEquation logistic regressionProsthetic heart valvesEmergency medical servicesGuidelines-StrokePrior strokeCohort studyIschemic strokeOlder patientsStroke onsetStroke severityDiabetes mellitusCenter HospitalStroke patientsAtrial fibrillationRisks and Benefits Associated With Prestroke Antiplatelet Therapy Among Patients With Acute Ischemic Stroke Treated With Intravenous Tissue Plasminogen Activator
Xian Y, Federspiel J, Grau-Sepulveda M, Hernandez A, Schwamm L, Bhatt D, Smith E, Reeves M, Thomas L, Webb L, Bettger J, Laskowitz D, Fonarow G, Peterson E. Risks and Benefits Associated With Prestroke Antiplatelet Therapy Among Patients With Acute Ischemic Stroke Treated With Intravenous Tissue Plasminogen Activator. JAMA Neurology 2016, 73: 1-10. PMID: 26551916, DOI: 10.1001/jamaneurol.2015.3106.Peer-Reviewed Original ResearchConceptsIntravenous tissue plasminogen activatorSymptomatic intracranial hemorrhageAcute ischemic strokePrestroke antiplatelet therapyTissue plasminogen activatorAntiplatelet therapyIschemic strokeGood functional outcomeHospital mortalityFunctional outcomeHigher oddsPlasminogen activatorDual antiplatelet treatmentGuidelines-Stroke registryRisk-adjusted likelihoodCardiovascular risk factorsRankin Scale scoreAmerican Heart AssociationAntiplatelet treatmentRegistry hospitalsRegistry patientsAmbulatory statusTPA administrationAdult patientsAntiplatelet agents
2015
Treatment patterns and short-term outcomes in ischemic stroke in pregnancy or postpartum period
Leffert LR, Clancy CR, Bateman BT, Cox M, Schulte PJ, Smith EE, Fonarow GC, Kuklina EV, George MG, Schwamm LH. Treatment patterns and short-term outcomes in ischemic stroke in pregnancy or postpartum period. American Journal Of Obstetrics And Gynecology 2015, 214: 723.e1-723.e11. PMID: 26709084, DOI: 10.1016/j.ajog.2015.12.016.Peer-Reviewed Original ResearchConceptsAcute stroke reperfusion therapyStroke reperfusion therapyShort-term outcomesTissue plasminogen activatorGuidelines-Stroke registryPregnancy-related strokeReperfusion therapyIschemic stroke patientsIschemic strokeNonpregnant womenPostpartum womenStroke patientsPlasminogen activatorPostpartum periodIntravenous tissue plasminogen activator useIntravenous tissue plasminogen activatorFavorable short-term outcomesTissue plasminogen activator useAcute reperfusion therapyCatheter-based thrombolysisGreater stroke severityMajor systemic bleedingNonpregnant women 18Symptomatic intracranial hemorrhageHistory of hypertensionTreatment and Outcome of Thrombolysis-Related Hemorrhage: A Multicenter Retrospective Study
Yaghi S, Boehme A, Dibu J, Guerrero C, Ali S, Martin-Schild S, Sands K, Noorian A, Blum C, Chaudhary S, Schwamm L, Liebeskind D, Marshall R, Willey J. Treatment and Outcome of Thrombolysis-Related Hemorrhage: A Multicenter Retrospective Study. JAMA Neurology 2015, 72: 1-7. PMID: 26501741, PMCID: PMC4845894, DOI: 10.1001/jamaneurol.2015.2371.Peer-Reviewed Original ResearchConceptsSymptomatic intracerebral hemorrhageRecombinant tissue plasminogen activatorMulticenter retrospective studyHematoma expansionHospital mortalityMedian timeRetrospective studyIntravenous recombinant tissue plasminogen activatorHealth Stroke Scale scoreParenchymal hematoma type 2Code status changeOutcome of thrombolysisStroke-Monitoring StudyComprehensive stroke centerHospital mortality rateOutcomes of patientsStroke Scale scoreTissue plasminogen activatorIschemic strokePrimary outcomeRtPA therapySecondary outcomesStroke centersSymptom onsetIntracerebral hemorrhageAssociation of Acute and Chronic Hyperglycemia With Acute Ischemic Stroke Outcomes Post‐Thrombolysis: Findings From Get With The Guidelines‐Stroke
Masrur S, Cox M, Bhatt D, Smith E, Ellrodt G, Fonarow G, Schwamm L. Association of Acute and Chronic Hyperglycemia With Acute Ischemic Stroke Outcomes Post‐Thrombolysis: Findings From Get With The Guidelines‐Stroke. Journal Of The American Heart Association 2015, 4: e002193. PMID: 26408015, PMCID: PMC4845108, DOI: 10.1161/jaha.115.002193.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAgedAged, 80 and overBiomarkersBlood GlucoseBrain IschemiaChi-Square DistributionChronic DiseaseFemaleFibrinolytic AgentsGlycated HemoglobinGuideline AdherenceHospital MortalityHumansHyperglycemiaLength of StayLogistic ModelsMaleMiddle AgedMultivariate AnalysisOdds RatioPractice Guidelines as TopicPractice Patterns, Physicians'RegistriesRetrospective StudiesRisk FactorsStrokeThrombolytic TherapyTime FactorsTissue Plasminogen ActivatorTreatment OutcomeUnited StatesConceptsTissue plasminogen activatorAssociation of acuteAcute ischemic strokeHistory of diabetesWorse clinical outcomesChronic hyperglycemiaClinical outcomesGuidelines-StrokeHospital mortalityAIS patientsBlood glucoseGlucose levelsPlasma glucose levelsBlood glucose levelsAdmission glucoseNondiabetic patientsPost thrombolysisIschemic strokeAcute hyperglycemiaDL increaseAcute correctionPoor outcomeAdverse outcomesOdds ratioHyperglycemia