renal disease, diabetes & lower extremity …
TRANSCRIPT
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RENALDISEASE,DIABETES&LOWEREXTREMITYCOMPLICATIONS…WHATWEKNOW&WHATWECANDOTO
BENEFITOURPATIENTS
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OBJECTIVES
• Understandthesignificantconnectionbetweendiabetes,renaldisease&lowerextremitycomplications,toincludediabeticfootulcers&utation.
• Understandthesignificantmorbidity&mortalitythatthesepatientsexperiencecomparedtodiabeticpatientswithoutrenaldisease.
• Understandtheoptionsthatexistwithinanephrologypracticeordialysisfacilityintreatingorreferringpatientswithulcersaswellastheclinicaloutcomes.
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WHATWEKNOW!
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Age-adjusted Prevalence of Obesity and Diagnosed Diabetes Among US Adults
Obesity (BMI ≥30 kg/m2)
Diabetes
1994
1994
2000
2000
No Data <14.0% 14.0%–17.9% 18.0%–21.9% 22.0%–25.9% > 26.0%
No Data <4.5% 4.5%–5.9% 6.0%–7.4% 7.5%–8.9% >9.0%
CDC’s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics
2013
2013
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2017CDCDataDiabeticFootUlcers(DFUs)&DiabeticFootInfections(DFIs)Rank#1
• 5.6billionambulatorycarevisitsbetween2007-2013• 6.7millionDFUsorDFIs1• RESULTS• Chronicconditions&associateddirectEmergency
Department(ED)/inpatient(IP)admissionhazardratios• DFIs–6.7timeshigher• DFUs–3.4timeshigher• CHF-2.56• CVD-1.57• IHD-1.54• Cancer-1.36• RenalFailure-1.21• Diabetes-1.12• Obesity-1.01
1Skrepnek,GH,Mills,JL,Lavery,LA,Armstrong,DG.HealthCareServiceandOutcomesAmonganEstimated6.7MillionAmbulatoryCareDiabeticFootCasesintheU.S.DiabetesCareMay11,2017
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TheCostisProhibitive
• Meanoneyearcostfromahealthcarepublicpayerperspectivewas$44,200fordiabeticfootulcer(DFU),$15,400forpressureulcer(PU)and$11,000forlegulcer(LU)1
• 33%ofthecostofdiabetesdirectlylinkedtothecareoflowerextremitycomplications2,3
• Inpatientadmissionsaccountfor74-77%oftotalcostsattributedtolower-extremitycomplicationsindiabetes4,5
1Chan;“Cost-of-illnessstudiesinchroniculcers:asystematicreview.”JournalofWoundCareVol26.No.4,April20172RogersLC,LaveryLA,ArmstrongDG.Therighttobearlegs–anamendmenttohealthcare:HowpreventingamputationscansavebillionsfortheUShealth-caresystem.JAmPodiatrMedAssn2008;98:3-53DriverVR,LaveryLA.Thecostsofthediabeticfoot:Theeconomiccaseforthelimbsalvageteam.JVascSurg4StocklK,etal.Acostanalysisofdiabeticlower-extremityulcers.DiabetesCare2004;27:2129-21345HarringtonC,etal.Acostanalysisofdiabeticlower-extremityulcers.DiabetesCare2000;23:1333-1338
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PrevalentMedicarefee-for-servicepatientcountsandspendingforbeneficiariesaged65andolder,byDiabetesMellitus(DM),Congestive
HeartFailure(CHF),and/orCKD,2014
U.S.MedicarePopulation
TotalCosts(millions,U.S.$)
PPPYCosts(U.S.$) Population(%) Costs(%)
All 24,496,020 $254,356 $10,803 100.00 100.00WithCHForCKDorDM 8,140,540 $130,220 $17,013 33.23 51.20CKDonly(-DM&CHF) 1,023,220 $15,109 $15,673 4.18 5.94DMonly(-CHF&CKD) 4,093,320 $47,846 $12,116 16.71 18.81CHFonly(-DM&CKD) 893,760 $16,955 $20,733 3.65 6.67CKDandDMonly(-CHF) 847,220 $14,856 $18,610 3.46 5.84CKDandCHFonly(-DM) 340,300 $8,829 $30,395 1.39 3.47DMandCHFonly(-CKD) 515,500 $12,599 $26,758 2.10 4.95CKDandCHFandDM 427,220 $14,025 $38,561 1.74 5.51NoCKDorDMorCHF 16,355,480 $124,136 $7,812 66.77 48.80AllCKD(+/-DM&CHF) 2,637,960 $52,819 $21,857 10.77 20.77AllDM(+/-CKD&CHF) 5,883,260 $89,327 $16,003 24.02 35.12AllCHF(+/-DM&CKD) 2,176,780 $52,409 $26,975 8.89 20.60CKDandDM(+/-CHF) 1,274,440 $28,882 $24,854 5.20 11.36CKDandCHF(+/-DM) 767,520 $22,854 $34,935 3.13 8.99DMandCHF(+/-CKD) 942,720 $26,625 $31,902 3.85 10.47
2016AnnualDataReport,Vol1,CKD,Ch6
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AssociationBetweenRenalFailureandFootUlcerorLower-ExtremityAmputationinPatientsWithDiabetes
• OBJECTIVE:Evaluatetheassociationbetweenfootulcers(DFU)andlower-extremityamputation(LEA)andCKDinpatientswithdiabetes.
• RESEARCHDESIGNANDMETHODS:Thiswasaretrospectivecohortstudyof90,617individualsenrolledbetween2002and2006whowereatleast35yearsofage,hadahistoryofdiabetes,andwerecaredforingeneralpractice.
• RESULTS:• 378patientshadanLEAand2,619hadaDFU• Referencegroup(group1[eGFR60ml/minper1.73m2])• ForDevelopmentofDFU,thehazardratio(HR)forgroup2(eGFR30and
60ml/minper1.73m2)was1.85timeshigher(95%CI1.71–2.01)andforgroup3(eGFR30ml/minper1.73m2)was3.92timeshigher(3.23–4.75)(allP0.001).
• SIGNIFICANCE:• PrevalenceofaDFUislikelytobe2-4timeshigherthanthestandard
diabeticpopulationMargolisDiabetesCare31:1331–1336,2008
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Generalpopulation§ Ulcerincidence2-7%§ Amputationincidence1%-1per100
§ Hospitalization20%
GeneralPopulationvsDialysis:footcomplications
Ndip:DiabetesCare2010Lavery,DiabetesCare2004Peters,Lavery,DiabetesCare,2001Uciolli,DiabetesCare1995
Dialysispopulation§ Ulcerincidence20%§ Amputationincidence10%-10per100§ Hospitalization38%
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LaveryLA:Theimpactofrenaldiseaseonsurvivalafteramputation.DiabetesCare2010
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AmputationLevel
DialysisN=128
ChronicKidneyDiseaseN=389
NoRenalDiseaseN=526
Foot 28.9% 40.4%
53.8%
BKA 43.8%
35.7%
23.9%
AKA 27.3%=71.1%
27.0%=62.7%
19.2%=43.1%
Dialysis:impactonamputationlevel
LaveryLA:Theimpactofrenaldiseaseonsurvivalafteramputation.DiabetesCare2010
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Survival Dialysis
ChronicKidneyDisease
NoRenalDisease
1Year 49.2% 23.4% 14.4%
2Year 57.8% 32.9% 23.0%
3Year 71.1% 43.7% 26.8%
5Year 82.8% 59.1% 39.7%
Dialysis:deathafteramputation2010
LaveryLA:Theimpactofrenaldiseaseonsurvivalafteramputation.DiabetesCare2010
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Hazardratio
95%ConfidenceInterval
p-value
Age 1.031 1.023–1.039 <0.0001CKDα 1.465 1.213–1.771 <0.0001
Hemodialysisα 3.912 3.071–4.982 <0.0001Below-kneeamputationβ
1.669 1.355–2.055 <0.0001
Above-kneeamputationβ
2.672 2.137–3.341 <0.0001
Theimpactofrenaldiseaseonsurvivalafteramputation:Riskfactors
α:referencegroupforcomparisonis‘norenaldisease’,β:referencegroupforcomparisonis‘footamputation’.HazardsratiosareestimatedusingExp(B).LaveryLA:Theimpactofrenaldiseaseonsurvivalafteramputation.DiabetesCare2010
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RelevantESCOQualityMeasures(QM’s)
ChronicDiseaseManagement• DiabetesCare:FootExam• DiabetesCare:EyeExam• RateofLowerExtremityAmputationAmongPatientswithDiabetes
• DiabeticRetinopathy:CommunicationwiththePhysicianManagingOngoingDiabetesCare
https://innovation.cms.gov/Files/x/cec-qualityperformance-ldo.pdf
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“Whydon’tyoudofootexams?”
• “AfraidofwhatImightfind”• “IfIfindsomething,Imayneedtodosomething”
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DiabeticFootCareManagementModelisEffective• MCOinSouthTexasover28months• 47%reductioninamputations• 38%reductioninhospitalizations• 22%reductioninlengthofstay• 70%reductioninSNFadmissions
LaveryLA,etal.Diseasemanagementfortheforthediabeticfoot:Effectivenessofadiabeticfootpreventionprogramtoreduceamputationsandhospitalizations.DiabetesResClinPract2005;70:31
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WHATCANWEDO!
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TraditionalPreventionStrategies
• RiskAssessment• Education-“do’s-don'ts”-Self-carepractices• Protectiveshoes–insoles• Regularfootassessment
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Sheehanetal.“Percentchangeinwoundareaofdiabeticfootulcersovera4-weekperiodisarobustpredictorofcompletehealingina12-weekprospectivetrial.”DiabetesCare.2003;26:1879-1882.
PatientSelectionCriteriaforAdvancedTherapies
MiMedxConfidential
BeginadvancedtherapieswhenDFUhasn’treduced
by50%in4weeks
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EpiFix®
• Dehydratedhumanamnion/chorionmembrane(dHACM)allograft
• ProcessedusingproprietaryPURIONProcess• Applicationsinacute&chronicwounds• Availableinmultiplesizes• ReimbursementcoverageinallMACsandselectpayers
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UniqueCharacteristicsofEpiFix
• EasyLogistics• Standardshipping• Ambientconditionstoragefor5years
• EaseofUse• Handlingcharacteristics• Embossed
• Testing/Sterilization• Livingdonortesting• Terminalsterilization
MiMedxConfidential21
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PURIONProcesseddHACMBilayerLaminateComposedofAmnionandChorion
• Cellspreserved• Not‘acellular’• Structurallyintact• Bioactive
• Extracellularmatrixintact• CollagensI,III,IV,V,VII• Laminin,fibronectin,proteoglycans
• Biologicalactivitypreserved• Growthfactors,cytokines,chemokines
Amnion
Chorion
H&E–cellnucleistaineddarkblue
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Fibroblasts
EndothelialCells
HematopoieticStemCells
BoneMarrowMesenchymalStemcells
AdiposeTissue-DerivedStemCells
Healthy&DiabeticTypeI,II
Biosynthesis
Migration
Proliferation
BiologicalActivityofPURIONProcesseddHACM1-8
dHACMCellandGFs
signaling
1. KoobTJ,RennertR,ZabekN,MasseeM,LimJJ,TemenoffJS,LiWW,GurtnerG.IntWoundJ.2013Oct;10(5):493-500.2. KoobTJ,LimJJ,MasseeM,ZabekN,RennertR,GurtnerG,LiWW.VascCell.2014May1;6:10.3. MaanZN,RennertRC,KoobTJ,JanuszykM,LiWW,GurtnerGC.JSurgRes.2015Feb;193(2):953-62.4. KoobTJ,LimJJ,MasseeM,ZabekN,DenozièreG.JBiomedMaterResBApplBiomater.2014Aug;102(6):1353-62.5. KoobTJ,LimJJ,ZabekN,MasseeM.JBiomedMaterResBApplBiomater.2015Jul;103(5):1133-40.6. WillettNJ,ThoteT,LinAS,MoranS,RajiY,SridaranS,StevensHY,GuldbergRE.ArthritisResTher.2014Feb6;16(1):R47.7. MasseeM,ChinnK,LeiJ,LimJJ,YoungCS,KoobTJ.JBiomedMaterResBApplBiomater.2015Jul14.doi:10.1002/jbm.b.33478.[Epubaheadofprint]8. MasseeM,ChinnK,LimJJ,GodwinL,YoungCS,KoobTJ.AdvWoundCare.2015Aug26.doi:10.1089/wound.2015.0661.[Epubaheadofprint]
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PublicationsonthebioactivityinPURIONProcesseddHACM
• dHACMisaStemCellMagnet™• Invivomousestudy:significantlymore
mesenchymalstemcellmigrationcomparedtoShamatday7
• Invivoparabiosisstudy:RecruitedHematopoieticStemCells–Resultsshowincreasedprogenitorcellengraftmentintragraft(c)andcomparedtocontrol(d)
OrganizingNewTissueBuildingBlocks
1.MaanZN,RennertRC,KoobTJ,JanuszykM,LiWW,GurtnerGC.JSurgRes.2015Feb;193(2):953-62.2.KoobTJ,RennertR,ZabekN,MasseeM,LimJJ,TemenoffJS,LiWW,GurtnerG.IntWoundJ.2013Oct;10(5):493-500.
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DiabeticFootUlcerRandomizedClinicalTrial(RCT)Outcomes• EpiFixwithStandardofCarevs.StandardofCarealone• 92%healedin6weekscomparedto8%forcontrol• Averageof2.5graftstoclosure
MiMedxConfidential
ZelenCM,SerenaTE,DenoziereG,FetterolfDE.“Aprospectiverandomizedcomparativeparallelstudyofamnioticmembranewoundgraftinthemanagementofdiabeticfootulcers.”IntWoundJ.2013Oct;10(5):502-7.doi:10.1111/iwj.12097.
Ulcershealed SOC(n=12) EpiFix(n=13) P-value
4Weeks 0(0%) 10(77%) <0.001
6Weeks 1(8%) 12(92%) <0.001
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DFURetrospectiveCrossoverStudy1
MiMedxConfidential
1ZelenCM.AnevaluationofdehydratedhumanamnioticmembraneallograftsinpatientswithDFUs.JWoundCare.2013Jul;22(7):347-8,350-1.2ZelenCM,SerenaTE,DenozièreG,FetterolfDE.Aprospectiverandomizedcomparativeparallelstudyofamnioticmembranewoundgraftinthemanagementofdiabeticfootulcers.IntWoundJ.2013Oct;10(5):502-7.3Unpublishedinternaldata.26
AdaptedChart
RCTDFUStudy2 RetroCrossover3
EpiFixmeantimetocompletehealing=4.2±3.1weeks
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ApplicationofEpiFix
SizeEpiFixusingsterileinstrumentsanddrygloves.
TrimEpiFixtocoverentirewound.Itisacceptabletooverlapmarginsby1mm.
Fenestrateifneeded.
EpiFixwillself-adheretowoundsite.Repositionifnecessary.Hydratewithsterilesalinesolutionifnecessary.Usesuturematerialortissueadhesiveto
fixateEpiFixifdesired.
Coverwithanon-adherentcontactlayer.Ifpossible,do
notdisturb.
Useappropriatemoisturemanagementdressings.
UseSteri-Strips™ifnecessary.
EpiFixiscompatiblewithoffloading,compression,&negativepressuretherapies.
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Patientscannotparticipateintheirownfootcare?
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MiMedxcanprovidevaluableinformationtoassistwithwoundcaretreatmentoptions!1. Woundcaretreatmentsupportinformation:
a) Treatment• Weprovidethesupport&informationifyoudecide
toset-upwoundcaretreatmentaspartofyourpractice.
b) Referral• Wecanprovideinformationonexistingadvanced
woundcaretreatmentfacilitiestoimproveoutcomesinpatientswithchroniclowerextremitywounds
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Summary• Patientpopulation• Severedisease…Highrisk• Highlevelofamputation• Highmortality• Opportunitytotreatpre-dialysispatientsinthenephrologyoffice
• PotentialtotreatESRDpatientsinthedialysiscenter
• Referraltoadvancedwoundcarenetworkinlocalgeography
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Questions???
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THANKYOUFORMOREINFORMATION
CONTACTSEANMCCORMACK
DIRECTOR,NEWMARKETINITIATIVES(770)767-1930