CyberseminarTranscriptDate:May9,2017

Series:HSR&DCareerDevelopmentAwardEnhancementInitiative

Session:ActionableInformationforAntimicrobialStewardship:HowDataCanCombatAntimicrobial-ResistantBacteriainVeterans

Presenter:MakotoJones,MD,MSCI;MichaelRubin,MD,PhD

Thisisanuneditedtranscriptofthissession.Assuch,itmaycontainomissionsorerrorsduetosoundqualityormisinterpretation.Forclarificationorverificationofanypointsinthetranscript,pleaserefertotheaudioversionpostedat

Moderator: Weareatthetopofthehour,sowithoutfurtherado, Iwouldliketointroduceourspeakers.Presentinghisresearchtoday,wehaveDr.MakotoJones.HeisanHSR&DCareerDevelopmentAwardeeattheHSR&DCenterofInnovation,Informatics,DecisionEnhancement,andSurveillanceknownasIDEASCenter,andthatislocatedatVASaltLakeCityHealthCareSystem. Joininghimtodayasadiscussantattheendofthepresentationisoneofhismentors,Dr.MichaelRubin.HeistheSectionChiefofEpidemiologyatVASaltLakeCityHealthCareSystemandaresearchinvestigatorattheIDEASCenteralsolocatedinSaltLake.Sowithoutfurtherado, Iwouldliketoturnitoverto you,Dr.Jones.

Dr.MakotoJones:Alright,thankyou.Appreciateit.SoI,mynameisMakotoJones.Thanksfortheintroduction. We'llgothroughtheseslides.Assomeofyouknow,afewyearsagotheWhiteHousehadlaunchedaninitiativeforcombatingantimicrobial-resistantbacteria,theCARB.That'spartofwherethiscamefrom, butthefocusisonreallyhowtousedatainthiseffortforVeterans,andyouknow,thethemeofactionableinformationwe'llseethroughout. SoI'dliketorecognizemymentorisMichaelRubin.He'sonthecallaswellasMatthewSamore,CharleneWeir,andTomGreene. Thereareotherswhoare,andthisisnotanexhaustivelistobviously,whohavebeenimmenselyvaluabletomeandmycareer,MatthewGoetzandChristopherNielsoninparticular. I'velearnedalot,andthere'salottogo.

Sopollquestion#1,andI'mbeingalittlebitflippant,butI'mcuriouswhenIsay‘antimicrobialstewardship’,howmanyofyouwillthinkHSRorhowmanyofyouthink‘what'santimicrobialstewardship’?

Moderator: Thankyou. Soforourattendees,Idohavethatpollquestionuponyourscreen. Sogoaheadandclickthe circlerightthereonyourscreennexttoyourresponse. Anditlookslikewe'vehadaboutalmosthalfouraudiencevote,butwe'llgivepeoplealittlebitmoretime. Theseareanonymousresponses. Okay,itlookslikewe'vegotjustabouttwo-thirdspercenthaveresponded,soI'mgoingtogoaheadandcloseoutthispollandsharethoseresults. Prettystrongmajority,81%ofrespondentssaidHSR!Andtheother19%saidwhat'santimicrobialstewardship? Sothankyoutothoserespondents.

Dr.MakotoJones:Thankyouverymuch.Well,hopefully,itsoundslikemanyofyouhavealreadybeenindoctrinated.HopefullybytheendeverybodycansayHealthServicesResearch.Appreciatethat.

Sothesecondquestionis,selecttherolethatbestdescribesyoujustsoIknowwho,kindofwhoisonthecall.Areyouasteward?Areyouaclinicianusuallyreceivingadvicefromasteward?Aclinicianthat'snotreallyheardofstewardship?Aresearcherinterestedin stewardship?Oraresearcherthatdoesn'tyetrealizealatentandbuddinginterestin stewardship?

Moderator: Iapologize. Ihadtotruncatethose,thatlastoptionthere. Okay,lookslikepeoplearealittlequickertorespond. We'vealreadygotatwo-thirdspercentresponded,andwe'llgivepeoplealittlemoretime. Soonceagain,justclicktheresponserighttherenexttoyouranswer;steward,clinicianusuallyreceivingadvicefromasteward,clinicianthat'snotheardofstewardship,researcherinterestedinstewardship,orresearcherthatdoesn'tyetrealizethelatentinterestinstewardship. Okay,I'mgoingtogoaheadandclosethatpolloutandsharethoseresults.And37%respondedsteward,8%clinicianusuallyreceivingadvicefromasteward,53%researcherinterestedinstewardship,and3%researcherthatdoesn'tyetrealizethelatentandbuddinginterestinstewardship. Andwehavezero,zeropeoplerespondedclinicianthat'snotheardofastewardship. Sothankyou,onceagain,tothoserespondents,andwe'rebackonyourslides.

Dr.MakotoJones:Thankyouverymuch.Soagain,IguessI'mbeingalittlebitlightheartedinsteeringyoutowardscertainthings,buttodaywhatI'dliketodoisdiscussalittlebitaboutwhatantimicrobialstewardshipis. Iwon'tspendtoomuchtimeonthatsincealotof,itsoundslikemostpeoplehavesomeframework,discusstheneedsofstewardship,outlinethecognitiveneedsofstewards,discussantimicrobialeffectsandwhywecareaboutthat,andthendecisionsupportincomplexsystems.

SoIthinkthisismylastquestion. Atthedawnofmodernmedicine,therewasnospecialtyofinfectiousdiseases. Soifyourecall,upuntil,youknow,the20thcentury,therewasnospecialtyinfectiousdisease. Isthatbecausecardiovascularcerebrovasculardiseaseandcancerwerethebiggestkillers? Infectiousdiseasehaslaggedbehindtheotherspecialtiesinmethods anddiscoveries? OrC,mostofwhateveryonehastreatedwasinfectiousdiseases?

Moderator: Thankyou. Lookslikerespondentsaregivingthisonealittlemorethoughtandthat'sperfectlyfine. Takeyourtime. We'vegotabout50%responserate,sowe'llwaituntilsomemoreanswershavecomein. Alright,andwe'reapproachingthe70%responserate,soI'mgoingtogoaheadandclosethatoutandsharethoseresults. Soitlookslike13%ofourrespondentsrepliedcardiovascularandcerebrovasculardiseaseandcancerwerethebiggestkillers,30%ofrespondentsreplieditlaggedbehindotherspecialtiesinmethodsanddiscoveries,and58%respondedmostofwhat everyonetreatedwasinfectiousdiseases. Sothankyou,onceagain.

Dr.MakotoJones:Thankyou!SoaccordingtoEdKass,whoisoneofthe,oneofsortofthefoundersoftheinfectiousdiseasesasaspecialty,makestheargumentthatinfectiousdiseaseswassomethingthateverybodypracticed,thatitwasn'treallyviewedasaspecialtyuntilthemortalityandthemorbidityoftheinfectiousdiseaseswentdownandtheothersbecamemoreprominent.Ifyouaren'tcurrentlyinterestedininfectiousdiseases,antimicrobialresistance,thisnextsetofslides,whichI'llgothroughasananimation,istrytoconvinceyou.So Carbapenem-ResistantKlebsiellaPneumoniaeisatypeofwhatwecallCRE.Youmayhaveheardofthat.NDM-1,KPCs,OXA-48saresomeofthenamesthatyoumayhaveheardinrelationtosuperbugsforsometime.SoCRKPmeansKlebsiellapneumoniaethat'sresistanttocarbapenems.

Sobackin2005,whichiswherewe'llstart,weseedifferentregionsrepresentedbydifferentshapes. We'veanonymizedwhichones. Redshadedfacilitiesrepresentplaceswheretherehasalreadybeenatleastoneoftheseorganismsdetectedbythispoint,andthentheblankones arewheretherehaven'tbeen. Thelinesrepresentplaceswherepeoplehavegonefrom,peoplewithCRKPintheirhistory,havegonefromonefacilitytoanother.Soatthispointyouseeabout a dozen facilities that have had CRE and you see movement between them of CRKP-positivepatients. Theredcirclesaretheretojustsortoflookat,soyoucanlookforthefirstlinetoseethattherearethingsliningup,andthenI'lljustgothroughtherestoftheseslides.

Youcanseethatwe,intheVA,areahappy sharingfamilyandthatmostofthefacilitiesbynowhaveseenatleastoneorganismthatiscarbapenem-resistantKlebsiellapneumoniae.

Sojustalittlebitaboutantimicrobialresistance,practice,outcomes,andstewardship,andhowtheyrelatetoeachother.Wehaveatimelinegoingfromlefttoright,andit'salittlebitcomplicated,soI'llwalkyouthroughit.Soultimatelywhathappensiswehave,lookingatantimicrobialpracticeatthebottomfirst,whatwewanttodoiswewanttoimproveoutcomes.Sothat,ingeneral,forasinglepersonfeelslikethatis,youknow,wetreatsomebodyandtheygetbetterortheydon'tortheyhaveanadverseeventortheydon't.Thatsortofthething,so there'salinethatgoesthrough.Theotherthing,though,thatinfluencespracticeispreviousantimicrobialresistance.Theproblemhereis,though,wehaveendogeneitybecause resistanceleadstopractice,leadstoresistancetopractice,toresistanceagain. Complicatingthingsevenmoreaboutpracticeandresistance,influencestewardship,whichinfluencespractice,whichinfluencesstewardship.Sowehaveafairlycomplexnetworkthatis,that,you know,bringsinoutcomesresistancepracticeandstewardshipthatwehavetounderstandand coordinatetogether.Resistanceis,youknow,andhowitrespondsisbasicallygovernedbyevolution,practicebythefusionofinnovations.

Sosomepeoplemay haveheardmeusethismetaphorinthepast.Hopefullyitdoesn'tgetstaleandhopefullyitmakessense.Icallitgettingontheantimicrobialstewardshipbus.Sooverthepastfewyears,antimicrobialstewardshiphasimprovedimmensely,andarecentpaperbyDr.AllisonKelly,NationalInfectiousDiseaseService,andmanyothers,andananalysisofantimicrobialuseinVAhaveseenimprovementswithanantimicrobialstewardshipprogram.Butoneofthethings,andsomepeoplemaytakeissuewiththis,soI'dbehappytosee,you know,whatquestionsorcommentspeoplehave,andmaybethisisnotacompletelyfair

characterizationiseverybodyisgettingonthisbus,andyoucanseetheheadsinthewindows. You know,youmaybegettingontheantimicrobial stewardshipbus,too. Ihopeyoudo. Butasyoulookforward,youseethatthereisactuallynobodyatthehelm. There'snobodyatthewheel. Nobodyisdrivingtheantimicrobialstewardshipbus,andthat'sanissue. Youimmediatelyseeaneed.Asanantimicrobialsteward,youhoptothefront,yougrabthewheel,andyoustartdriving.So that'sgreat.Everythingyoudo,everyturnyoumake,whenyouputonthebrakes,whenyouputontheaccelerator,youholdthefateofnotonlyyourself,buteverywhereyougo,youtakeeverybodyelseinthebustherewithyou.Theproblemisyoustilldon'tknowwhereyou'regoing.Asyou'redrivingthisbus,passengersstartcallingoutnamesofplacesthattheywanttogo,soyou'regoingtohavetofigureoutwheretotakethem.Problemisyouprobablyneed amapinordertofigurethisout.Themapinourcaseissomesortofrepresentation,somesortofframeworkthathelpsustounderstandhowtooptimizethesituation.Inthiscase,whatpeopleusuallytrytodooncetheyhaveamapandoncetheyhaveanideaofwheretheywanttogo,theytrytopickaroutethatminimizesthetotaldistancetraveledandalsominimizesthewaittimesoftheindividualpeopleonthebuswaiting.

Sowe need to clarify goals, and oneof the issues of antimicrobial stewardship isworking on is whosegoals. Weneedtoclarifyeffects. Andwhatdowemeanbyeffects? Effectsarereferringtothosethingsthatantimicrobialsdotopatients,thatantimicrobialsdotothemicrobiomesofthosepatients,andwhatthosemicrobiomes,thoseorganismsthatmaybeselectedfororproliferateduetotransmissionandthereforethecareofotherindividualsthatpersoncancomeintocontactwith,effectsonmeandyou. Soneedfordecisionsupport,sothesecanbetheinformation,aswe'lltalkaboutlaterinthetalk,canbeenormousandtheycandifferbyindividualdecisionmaker.

Sowe'lltryandfleshoutsomeoftheneedsaswegoalongsothatwecangettheantimicrobialstewardshipbustodoabetterandbetterjobofdeliveringcaretopatients.Asyouknow,ItrytopointoutsometimestheVAhasbeenworkingonandimprovingaccessandhasbeendoingthatinmanycases.Theproblemis,unfortunately,infectiousdiseaseshavejumpedontohumansocialnetworkssincetimeimmemorial.Andasaccessincreases,aspeoplereceivemorehealthcareexposure,theproblemswithantimicrobialresistancemayactuallyincreaseaswell.

Sowhat'stheholdup?Whycan't,whydoesn'tourbushaveaproperitineraryallfleshedout?Oneoftheproblems,youknow,I'mtryingtoillustratehereinthisslidesetisthatwedon'thaveahugenumberofgoodrecommendations.Youcanseethatalotofwhatwehavein infectiousdiseasesisthegraythere,levelthreerecommendationsfromrespectedauthorities,clinicalexperience,descriptivestudies,orreportsofexpertcommittees.Wewouldlovetohavesolidbestpractices-levelevidence,butinthemeantimethebusisstillmovingandwe'vegottofigureoutwhattodo.

Anotherinterestingproblemthatwefaceinantimicrobialstewardshipisthat,imagineifeverybodydidthesamething,everybodypracticed,youknow,gavethesameantimicrobials forthesamethingsinalloftheirfacilities. Whatthatdoesisitcreatesanenvironmentwherecertainbugs,certainbacteriacanspreadthrough,andoncetheyspreadfromone,theycanspreadtothenext. Theyspreadtothenextrelativelyunimpeded. Weseethisinecologywiththeinvasivespeciesandareconcerned,youknow,basedonsomeexperimentsthathavebeenperformed as well as on theoreticalframeworks. But in thiscase, a lack of diversity ofantimicrobialpracticemaybeasetupforcertainbugsspreadingfromfacilitytofacility.Soingeneral,formanytypesofpracticeswhereyouhaveabestpractice,youwanteverybodydoing thesamething. Thetrickythingistherearesomepracticesinantimicrobialstewardshipthatarelikethat,buttoomuchconformityinwhichantimicrobialsareactuallychosenmayactuallycauseaproblem.

SogettingontomyCDA,thespecificaimsthatwehadoutlinedare,andwe'llgothroughalittlebitofworkineachofthese,tocharacterizetheinformationneedsanddecision-makingpatternsofstewardswhenmakingantimicrobialrecommendations.Two,identifypredictorsofcoverageandemergenceofresistanceusinglocaldata;andthree,developaclinicaldecisionsupportsystemthatnudgesandpromptsstewardstouselocalhospitaldataandtesttheinfluenceonstewards.

Sowhatwedidwas,andI'vehadalotofhelpfromDr.Weirandalso,andStaceySlagerindoingthesethings.WeusedamethodbroughtfromnuclearengineeringasawayofstudyingdecisionmakinginthewildcalledRasmussen'sDecisionLadder.InRasmussen'sDecisionLadder,thereare,itallowsforcomplexdecisionsormentalprocessestobemappedinawaythatcansupportinformationtooldevelopment,evenifpeopleuseshortcuts,evenacrossexpertand noviceleveldecisionmaking.Sotheinterestingthingisweperformedsomeoftheseinterviews,andevenwiththeflexibility,itseemedlikeasquarepegfittinginaroundholealotofthetime.It,youknow,we'daskquestions.Itseemedexcessiveredundantandwithsparseanswers.Otherthingswedidn'treallyfeellikeweweregettingasmuchaswewantedback.

Theotherthingisweworkedonthings,triedtointegratedual-processtheory,somanyofyouare probablywell familiarwiththat, withthework ofdiversity andKahneman. Maybeyou'vereadKahneman'sThinkingFastandSlow.Thekeypoint to thinkingabout thatissometimespeople,includingexperts,willlookatapieceofinformationandcometoalightningfast,usuallylightningfast,effortlessconclusion.Theywon'teventhinkaboutthinking.Andatothertimessomethingmightcomeupandtheythinkdeeplyaboutaproblemandworkonit.

Sointryingtodothis,youknow,welookedatourinterviews,wedidafewiterations,andcameupwiththesebasicconstructs. One,soactivation/alerts,tryingtogetatthecontextandvarioustriggersthatbringsomethingtoone'sattention,youknow,inthiscaseanantimicrobialstewardshipproblem. Theappraisalandinterpretation,sogettingatthe,whatdotheyneedtodotoget,andwhatarethethoughtprocesstogetatthegistoftheproblem. Youknow,theinformationtoact,sowhatdotheywant. Theactivity/action,sowhatdotheydo. Expectation/evaluation,figuring outwhatmoreneedstobedone. Theinformation

gatheringstep,sodotheyneedmoreinformationandinformationstrategy,wheretheygetinformationfrom.

AndI'llshowyousomemorethingsinjustasecond,butwhatwe,afteraseriesofinterviewsin theVAsystemweactuallypilotedaroundhere,manythankstomanylocalstewardsfromtheIntermountainandothersystemswhoparticipatedinpreliminaryinterviewswhilewewereworkingthisout,wecameupwithamodeltryingtointegratethesetwoideasinawaythatworkedbetterforantimicrobialstewardship.Sowe'llgothroughthisquickly.I'mjustthinkingthatmaybe,sothisisalittlebitWaterworld-y,andsobearwithme,sohopefullyit'sbetterthanthemovie.

Wehavetriggeringinformation. Thatcomesdown,usuallystartsthe,startstheprocess. One,two,three,four,five,six,sevenreveal,relatetotheprocessesthatwe'veseenonthelastslide. This smallarrowgoing upisreally meanttoshowhow it'shardfor, youknow,water toevaporateandbebroughtuptotheclouds,butreallyeasybecauseofgravity,tobringthings down. Sosystemone,ifeverybodyremembers,istheautomaticfastwayofthinking. Systemtworepresentedbythecloudsisslowandyoucanthinkofevenhowmuchwaterisinthecloudsversushowmuchwateris,youknow,onthe surface.Anotherwayofthinkingofitis remember,I'mthinkingofwaterflow. Systemone,thatautomaticprocess,harnessesandhasamuchhighercomputingcapacity,ourbrain,andourbrainthendoessystemtwo. Sothings willgenerallystayinsystemone,occasionallygetskickeduptosystemtwo,butitusuallycomesrightbackdown. Sothere'sthisprocessasyougofromsteptostep. Youmayjuststayinsystemone. Occasionallyyoupopintosystemtwo. Welookthroughthat.

Anotherinterestingthingiswhenwewereinterviewing,andthisissomethingthatDr.Weirhaslookedalotinto,there'ssomethingthatstewardsappeartotendtodofairlyfrequently,whichistheysaywell,I'mgoingtoputsomethingoncruisecontroluntilsomelaterstep,someinformationcomesback,andthenwe'llpopbackintosystemtwo. Sotheyreallydon't,aren'tgoingtoconsideranythinguntilthathappens. Sotheysetaninnertriggeringmechanismthatreallyisnot,doesn't,theydon'tthinkaboutuntilthattriggerisset. Soitisfascinatingathowcommonthisappearedtobe.

OtherthingsthatwewereinterestedinthatcameoutduringtheseinterviewsisborrowingfromKurtLewins"ForceFields". Thereseemedtobethingsthatpoppedpeopleintoandoutofsystem1. Againsystem1,thatfastformofeffortlessthinkingbeingthedefaultandsystem2beingthosethingsthatareeffortful,thatdependingonhowseverethepatientwas,culture,howpeoplepersonallyvaluedsigns,theirowncuriosity,theiraccesstothebedside,power,legitimacy,socialinfluence. Thosethingsappeartoinfluencewhethertheypoppedinandoutofsystem1andsystem2thinking. Soforexample,bedsideaccesswassomethingthatfrequentlycameup. Moststewardsfeelthatbedsideaccessis afairlyprivilegedthingsothattheydon'tgotothebedside,ordon'tgettogotothebedsidetogatherthosesortsofinformation. Frequentlywhenwedon'thavethatsortofinformationandareinsystem1,though,wedon'teventhinkaboutwhatwouldbeavailable. Sowemakedecisionsbasedjustontheinformationpresent. Sofrequentthingsthatpoppedpeopleintosystem2werefear,

frequentlyduetoseverityofillness,certaintypesofdiagnoses,orfearofwhatotherpeoplewouldthinkofthem,socialinfluence. Someoftheexamplesofwhatfellintotheseconstructsforactivationalert,typicallytheywouldfirstoffreceivealertphonecallandreceiveconsultation. Igroupthoseintothosethingsthatarepassive,thatarebroughttothesteward. Theymightsearchfororders,youknowIVordersandthosetypesofthingswereviewedandcommercialoff-the-shelfsoftware. Thosetypesofthingsareactiveand,youknow,someofthemmentionedthatbesidesthosethattherewasadecentamounttheymightevenmiss. Forappraisal,howtheycameupwiththeirgutassessment,firstoff,mostpeoplewantadiagnosis,thentheywanttoknowtheantimicrobials,theywanttoknowguidelines,andlastly,theymightthinkabouthowthingsmightminimizeresistance.

I’ll speedthisupsoIcangettootherthingsalittlemoreexpeditiously,buttheylookforinformationthatwaseasyandtheninformationthatwasharder.Foractivityandactions,theytriedthosethingsandstartedmakingrecommendations,butasthingsgothardertheymadefollow-upplans,oraskedforconsultation,orsometimesevenwentupthechainforthosethingsthatevaluatingwhethertherewasmoretodo,theysetupfollow-uplabsforinformationgathering.Iftheinformationwasinconsistentorincoherentitoftenpromptedthemtogobackandtheinformationstrategywastoreviewthechart,calltheteam,andifnecessary,seethepatient.SothisisgoingalittlebitslowerthanIthoughtsoIamrushing,Iapologize.Idowanttogetto someoftheotherideasthoughaswell.Wewantedtopredictcoverageandresistance inanimperfectsystemwherehumancreativityispotentiallytheissue. Sooneofthethingsweneedtodoinantimicrobialstewardshipislookforantimicrobialeffect.SowhatIamgoingtotalkaboutinthenextfewslidesisfairlycontroversial,Ithink.OfanyposterthatIhaveeverstoodbefore,Igotmoreglancesaskewforthisthanforanythingelse.

But, here is thething that prompteda look intothis specific issue. Over time inboth ICU andMed/Surg,wehaveseenasignificantincrease,32-52%intheICUand20-38%inMed/Surg ofVancomycinuseovertime, or at least between 2005 and 2010 whenwelookedatthis. Concomitantly,inthesameenvironmentswehaveseendecreaseswhichIthinkmostofyouareprobablynotsurprised. Youhaveseenprobablyhigh-profilearticlesandwell-readjournalstalkingabouthowMRSAhasbeendecreasingintheVAforquite some time, butwewerewonderingwhyanti-MRSA agentusewouldbecontinuingtogoup,up,upwhileMRSAcontinuedtogodown.Sowhatwedidtotakealookatthisiswell,we said well,let’stakealookandseeifwecanusesomecausal inferencemethodssothisworkedwithBrianSauerhereinSaltLakeCityusingamatchingweightsapproachthathehasusedandprogrammedandTomGreeneandothers haveworkedontoseewhethertheinitialchoiceofantibioticsinindividualswhoweregivenantibioticsand survived, well not survived, whowerestillinthehospitalonday4,whetherthatledtoadifferenceinMRSAoutcomesafterday4. Wedidthisanalysisandbroughtinalargenumberofconfounders,differentdiagnoses,comorbidities,otherfeaturesoftheadmissionandcompared,soweseetheunweightedandthentheweighted. Bothoftheweightedratiosarenowinsignificant,bothforMRSAacquisitioninthelikelihoodthatsomebodydidn’thaveMRSAwhentheywereadmitted,togetMRSAortohaveMRSAinfectionthattheydidn’tcomeinwithtothehospital,sowesaidwellwecouldprobablydoalittlebitbetterthanthat. Sowedidacompetingrisksregressionlookingattheoneffectsofanti-MRSAtherapyonMRSAacquisition positivecultures.SoonleftsideweseeMRSAacquisition,theredlineshowsadecreasedriskwhilepeoplewereonanti-MRSA therapy.Soforthe cliniciansinthegroup,thisisprobablynothugelysurprisingwhenyouputsomebodyonVancomycin,otheranti-MRSAtherapytheyareprobablysomewhatlesslikelytohaveMRSAacquisitionthan otherwise.WhenyoulookatMRSApositiveculturesweactuallyseethatit’sflipped,sopeopleweremorelikelytohaveaninfection.Thisstill doesn’t really makesense andI was concerned,especially whenI looked atsomeofthecasesthattherewasmajormisclassificationproblemsgoingon. Sotheissuewithacquisitionforbackgroundisweswabpeople'snoseswhentheyareadmitted,weswabthemwhenthey’retransferred,andweswabthemwhenthey’redischarged. Sothesearenotcloselytied to their infectionstatus. Theproblem is MRSA positiveculture is drawn whenthereisaculture. Peoplewillfrequently,inreadingthesenotes,peoplewouldfrequentlygetsignsandsymptomsofinfection,theywouldonlygetbloodculturesandstartVancomycinimmediately,then4or5dayslaterwhen none oftheculturescamebackandtheywerestillfebrile,theywouldgotosurgeryandcomebackMRSA,etc.,etc.

Sotheproblemherewas, inthelittlefigureontheleft,wehavepositiveculturescomingon latewhenpeoplewerestartedonanti-MRSAtherapy.Soitisreallya misclassificationexposure.Whenwetookalookatasmallercohort,lookingatonlythosewhohadessentiallyadifferentindicationforanti-MRSAagents,saycoag-negativestaphblood streaminfectionestablishedbymultiplebloodcultures,positiveforcoag-negativestaph,we see that, andIhavethecolorsflippedunfortunately,thattheanti-MRSAagentsappeartobepotentiallyprotectiveforMRSAinfection.Nowasfarasthedirecteffectgoes,thatshouldn’tbesurprisingtomanypracticingclinicians.Sothatifyougiveanantibioticthatkillsabacteriathattheyarelesslikelytoacquirethatbacteriaorbeinfectedbythatbacteriawhiletheyareon thatagent.Theproblemisthatconsideringthat50%ofalladmissionsreceiveatleastonedoseofantibioticandprobably20-40%dependingonthehospital,ofthatisVancomycin. And thatVancomycinisbeingadministeredtothoseprobablyathigherriskofMRSAacquisitionorinfectioneveniftheydon'talreadyhaveit,thatthelarge-scaleadministrationof anti-MRSAantibioticsmaybeinfluencingthedowntrendofMRSA.Solookingintoantibioticseffectsisonething.Sotheotherpieceis,whatcanwedotopredictthepresenceofMDRO.

Soinonepaper what welookedat is well,howmuchdoesaMRSApositivescreenpredictthepresenceofothermulti-drugresistantorganisms, sorry I didn’t spell that out before I said it. Thatactuallydoesfairlywell. Itactuallycapturesthebulk.WetitledthisthecollateralbenefitofscreeningpatientsforMRSA.Lookingatsortofanunintendedconsequencethatactuallymightbegood,it meansthatforallofthosethatarebeingscreenedand putundercontactprecautionsforMRSA,we’reactuallygettingpotentiallya lot ofthe silent MDRO. Whatwe wanted todo a littlebit is to actuallyskip theslidesforthesakeoftime,istogetintohowwecanusebigdatatopredictusefulthings. Thegrowthofantimicrobialresistantorganismsbeforetheyactuallygrow,butwhenwegettheculture. Sowithanareaunderthecurbofpoint8-3forthisonewewereabletopredictthegrowthofCRKforcultureandtherearecurrentlymodels,workdonebyChrisNielsonandCliffordBakerthatactuallydoabitbetterandhavethecapabilityofpotentiallydoingalotbetter,aswellaspredictingthegrowthofmultiple organismsallatthesametime. Justafewthingstobringuphere,whenwedidthis,thethingthatisoftenleftoutofmost largestudiespredictingresistantgrowthis that the biggestpredictors,mostofthemwereahistoryofresistance.IthinkIactuallyhavemoreofthisslidecutoff,butmostpeoplearelookingata history ofantimicrobialexposureintheindividual,butitappearsthatalotofthatinformationismanifestedintheresistanceitselforthattheyarecollinear.Iwillskipoverthis, but alsoforthesakeoftime,takeawayinthisparticularsectionbeingthatantibioticscanhavetheleastdirecteffectsonorganism,sothattheantibioticsthatasinglepersongetmayinfluencetheresistantinfections,notjustCdiff,butotherthingsthattheygetinthefuture.So,twothatwecanpredictantimicrobialresistance,andthree,thatweneedtoworkmoreonunderstandingindirecteffects,i.e.thoseeffectsthatif personAgetsanantibiotic,thenunfortunately,personBmightgetaresistantinfection.

ThelastmajorsectionthatIwanttotalkabouthasmostlytodowithinformatics. Sowelookatwhatareinformationneeds,facilitatorsandbarriers,whatdopeoplewant,howdotheyinterpretinformation,knowledgeandsoforth. Thenwelookedatwaystoaugmenttheknowledgebase.Sothis, maybepeoplearefamiliar withMaxwell'sdemon.Maxwellwasfamousinphysics,buthepositedthatiftherewasademonwithinfinitecomputationalpowerandthiswayofopeningandclosingatrapdoor,thatitcoulddefythesecondlawofthermodynamicsandtakenormalroomairtemperatureandmakeonesidehotandonesidecold. This, without getting into information theory, it’snowbeenknownthatthecomputationalexertionofMaxwell'sdemonwouldactuallymakeitsothatitwouldgeneratewhateverthedemon'sbrainwasmadeoutof, would generate heat,andtherewasactually nowaytogetoutofthisparadox. Butfrequentlywewanttodoimpossiblethings withmassiveamountsofinformationandcomputationalpowerinordertogetthingsdone. WhatIwanttoshowinsteadisthat whatwehavehereisaveryinterestingsystemandIthinkHealth Services Research has it exactlyright.ThisisborrowingalittlebitfromknowledgeinformationdataframeworksandIamusingawaterwheeltoshowyousortofwhatthatlooks like.SoCesarHidalgosaid"knowledgeisheavy".SoifyounoticeI representeddataasairorwind,informationiswater,andknowledgeasthewheel,thewheelwillturntocreatework. Sotheinterestingthinghereisthatdataisdata,informationaspeoplefollowsportsandpoliticalforecasting,NateSilversaysinformationis dataimbuedwithmeaningthatwhenyouhavedataimbuedwithmeaning,itactuallystartstointeractwithaknowledgeframework. Whenitdoesthat,itcanhelpdrivedecisions,whichimprovesthings. And we’ll come back to this thing a little later. Expandingonthisalittlebitandshowinghowinformationworksindifferentsettings. Thereareactually,thisiscalledtheCynefinframework,don'ttellmehowthespellinggetstothat,apparently,it’s aWelshthing. Westartinthelowerrightcornerinsimplepractices,complicated,complex,chaotic.Theinterestingthingisthatfor,andIwillexplainthesethingsalongtheway,simpleinthebottomrightcorner,youcanusebest

practices. Thereisgoodsolidevidence,youarenotgoingtogetawholelotofweirdstuffthatcausesexceptionsandingeneralyouaregoingtoeither fully automate it,oryouaregoingtouseahumanbeing. Typically,youarenotgoingtointegratethosesystems. Forcomplicatedsystems,we’llshowyouthatcomplicatedsystemsarethosethatdonotmanifestcomplexityand Iwilljust leavethedefinitionof thatisthe butterflyinChina, tornadoinTexas thing, youknow,weirdthingslikethatdon'thappen. Itcanbecomplicatedlikeclock,butthosethingstypicallydofairlywell, there was a question, sorry. Withautomationofthesystemcomplexissystems whereyoucangetbutterflyinChinaeffectsandchaotic,andwewillleavethattoMaxwell'sdemonfornow.

Iamgoingtotrytowrapupfairlyquickly.Sofortheantimicrobialstewardsintheaudience,youmayhavefiguredthisout.Youmaybewonderingstill,whenyougetfeedbacksayingyourantimicrobialuseis589antimicrobialdaysper1,000patientdays,youmaybeasking‘isthis good,orisitbad’?‘Which part of it is good or is it bad’? Andifit’sbad,howdoyouknowhowtofixit.SowithGreaterLosAngeles,whatwe’vebeentryingtodoistolookatcontext,tomapthesethingstodecisionpointstohelppeoplegaintraction. And I showedyouthisequationalittlebittooearly. WhatIamtryingtosayisthatwiththeequation, andIdon'twantyoutotrytounderstandit,butbasicallytojustsaythatwhenwebuilduptheknowledgebasetosay,wellthereisthisequationthattellsus, thatanchorsthingstodecisionpointsthatactuallyworksprettywellwhenweestimatevariousparameterslikehowoftendoyoustartantibiotics,howoftendoyoustopantibiotics.Thecorrelationisactuallyquitehigh.

Whatwecanactuallydo,andyouknowwesubmittedtoHSR&Donthistopic,isyoucanlookatdifferentantimicrobialclasses,wecangettheparametersandthenwecanpredictantimicrobialuseandyoucanseeourpredictionin the columninthemiddleandtheactualantimicrobialuseinthecolumnrightnexttoit,andwecantellyouwhattochangetogetthemostchangeinantimicrobialuse.Soyoucanloweryourprobabilityofstartingantibioticsonadmission, youcan loweryourprobability ofstarting antibioticsifthey havepreviouslynot beenonthem,youcanincreaseyourprobabilityofstoppingantibiotics,etc. I’llleaveit there,butasacomplicatedsystem,youcanactuallydoalot. Complexantimicrobialdecisions,areinfact,moredifficult. Sowhatworkedbeforewillnotnecessarilyworknow,itrequiresthinkingmoredeeply,wewon'talwayshavetherightanswer. Iamgoingtoskipoverthisfornow,itcouldwork.Basically,Iwilljuststophere,youcanreadifyouwant,butIamjustgoingtostoptoskipoverit. InworkinGreaterLosAngelesinatimeoutwhereweaskedpeopleto,onday3,torevisitwhethertheyreallyneedantibiotics. Wegavethemahandoutthattrendedvitalsigns,gavethemmicrobiologydataonantimicrobialuseandtherewasalsoatemplatethatwassortofaself-approvalofantibiotics. Itwasinterestingbecausepeoplereallydidsaythatitdidmakethemthinktwice,suggestingthatwecaninfluencebehaviors. WeareinacurrentgreatprojectthatwehavebeenworkingwithGreaterLosAngeleswith. Ihavelearnedalotaboutinformationanditsrolewithknowledgeanddata.

IamgoingtoskipoverthissothatIcangotosomethingfairlyprovocativethatmaybe ill-advisedtoshowatthispoint,butthequestionis,‘canweassessthecomplexityoftheinformationenvironmentofpeopleastheyarepracticingsothatwecantailorwhatwe’readdingtothatcomplexitytotrytodoabetterjoboforganizingtheinformation?’. SowhatIamactuallydoinghere is showing you,forpneumoniaadmissions,I’m looking at the order,wecanlookatwhatsomecallentropy,somecallcomplexity,somecallsurprise. Whatwe’reactuallydoingisto, it’sawayoflookingatanorder,weightingitbyhowrareitis,sotherarer somethingis,themoreweightwegiveitandthenlookingateverydayinthehospitalization, thehospitaldayandlookingatthecourse.Soifwelookforexampleatthemiddlerightcolumn,westartfromwhatappearstobeafairlylowentropyfortreatmentordersandforinformationgathering,butasthedaysgobyweseealargeincreasewhichmaysuggestanescalationofcareandofrequestsforinformation. So x-rays, labs, and so forth.Onthesecondpanelonthebottom,weseeapatternthatsuggestsde-escalation.Whenwelookattheinformationenvironment,so this is I thinkthelastslide before I’ll conclude.Ingeneral,weseetheactivetreatmentorderssoagain,thesearemedicationsandtreatmentproceduresandsoforth. Allweightedandsometogetherandthen allofthosecourses,welookatthelowestcurvethatrepresentsallthosecourses,weseeaflattish,butsomewhatincreasingincreaseintheinformationasthepatientstaysdayafterday,whichIdon’tthinkisterriblysurprising,butweseeamoresteepcurvethatIfind interestingasthedaysgoby.

SoIwanttoleavetimefordiscussionandcertainlycancomebacktothat. Ihaveotherthoughtsaboutthat,butIwillgotobasicallysaythankstoallofmymentors,collaborators,advisors,etc.IamworkingfuriouslyontheotherthingsandIfinditfascinatingeverydaycomingtowork.Sowiththat,Iwillopenitupforquestions.

Moderator:Thanks.Ifitisalrightwithyou,actuallywewillgoaheadandturnitovertoDr. Rubinforhiscomments.

Dr.MichaelRubin:Ohwell,Ididn'thaveanycommentsreallyprepared,butcaneverybodyhearmeokay?

Moderator: Yeah.

Dr. Michael Rubin: IthinkI’lljustsayacoupleofthingsandthenwe’llopenitupforquestions.I just wanted to say that youknow,Makotoisjustdoingafantasticjobapproachingasubjectlikeantimicrobialstewardshipfromastandpoint,Ithink,thathasn’tbeendonetoagreatextent,giventhatitisarelativelyyoungfielditself,but alsoit’satypeofdecisionmakingthatisinmanywaysunique,buthasveryparticularchallengestoovercomeandIthinktheapproachesthatheistakingwithhismentorsitisaverythoughtful,theory-basedtypeapproachthatIthinkcanleadtosomeveryrealadvancesandasubjectthatIthinkisjustverycomplicatedanddifficultbecause it’s sort of rooted in specific types ofbehaviors. And I think like he saidearlier, there isn’t agreatdealofreally solidevidencebehindsomeofthethingsthatwewouldlikepeopletodo,andthisisawayoffillinginsomeofthosegapsand coming up with ways ofaddressingsomeofthoseissues.SoIthinkhopefullyyouhavegottenthesensefromthispresentationthatheisthinkingverycreativelyaboutthisproblemandcomingupwithsomereallyintriguingsolutionsforthis. Ithinkthat’sallIwouldsayandmaybeopenitupforquestionsthen.

Moderator: Excellent, wellthankyoutoyouboth. For ourattendees,tosubmita questionoracommentpleasegotothecontrolpanelontheright-handsideofyourscreenandclicktheplus, I’m sorry,thearrownexttothewordquestions. Thatwillexpandthedialogbox andthenyoucansubmityourquestionorcommentthere. Thefirstone,youmakewonderfulmodels.Regarding theSwisscheeseandsimilarityoftreatment,isthereawaytoensuredifferences inthecheeseslicesintreatmentratherthansameness,ifdifferenceshavebetterdisease controlresults?

Dr.MakotoJones:Thatisagreatquestion.Soone isthatwehavetoestablishhowthatworks,butoneway,sowhatwe’redoingistocreatewaysoffeedingbackwhat’shappening.Soonethingthatwecandoforthatistofeedbackwhatotherpeoplearedoing.Therearewaystoanonymizethat,buttoreallygetintohowpeoplecanthinkofhow aparticulartreatmentoftheparticularindividualcanbeafact,or treatmentcanimpacttheoutcomesofotherpeople. Onewayofdoingthatwithafairlysimpleonedimensionalmeasureisactuallyusedintheentropymeasurethatwelookedatbefore. ManyofyouwhousethecomplexityscorethatisusedtorankVAMedicalCenters,willnoticethereisaHerfindahl index.TheHerfindahlindex forresidencyprograms.Theformula forthatistheexactsameastheentropyinformationcontent, informationcriteria. Surprisetheyareallsortofsynonymsforthesamesortofthing. Diversityindexisanotherone,soessentially,wecouldgetatthediversityindexoftreatmentatafacilityandwhattypesofthingsincreasethediversityoftreatmentandwhatkindofthingsnarrowit. Ithinkthat’sagreatquestion.

Moderator:Thankyou.Thenextquestion,thismakesareferencetoyourCDAcareerpath. Howmuchofthisfollowedyouroutlinewhenyouoriginallyappliedandhowmuchveeredoffcoursefromyouroriginalresearchintentions?

Dr.MakotoJones:Sothatisagoodquestion.Alotofithasbeenplannedfor,buttheinterestingthingisthatmanyofthesubtletieswerenotanticipated,whichmakesit

exciting.Forexample,foraim one,investigatingthebarriers andfacilitators,thecognitiveworkflowandsoforth,wereall, that was allintheplan.Butthesortof thethingsthattheyfedbackwerenotallanticipated,atleastnotbyme. Theneedforasynchronouscommunication,theneedtoestablishbasicallyfuturetriggerstohavenegotiatingprocesseswithcliniciansthatoccuroverdayssothattheyfrequentlymake deals. So okay I’llgive you this antibiotic, but at two days’ time if something does nothappenthenwe’re gonnaswitchit,butthentheyforget,sotheneedsforthosetypesof things.Forantimicrobial effects,as weget into it,those typesof things,I’msure I willbesurprisedsomemore. Thelast aimhasbeeninterestingbecausealotofthethingsthatIhadoriginallywrittenwerethingsthatIhadanticipatedwouldbetheirinformationneeds,butmanyofthethingsthatthey’veaskedforhaveactuallybeendifferent. Sothebigthingthereistoactuallyfillthoseneeds,butatthesametime, to create. Oneoftheissuesisthatbecause nobodyhasafirmgrasponhowlocalresistanceandantimicrobialuseeffectsfuturelocalresistanceyet. That’s sort of stillkindofup intheair. Whatwearetryingtodoistodelivermoreandbetterinformationsothatthepeoplecanfigureouthowtousethatinformationtodothatandbecausethat’srelativelynew,weareblazingnewtrails. Sometimespeoplethinktheyknowwhattheywant,butwhentheygetit,that’snotwhatitis,sothere’ssometrialanderrortoo.

Dr.Makoto Jones:Thank you for thatreply. Whilewe wait for anyfurther questions orcomments to comein, do youhave any concludingcomments you’dlike to make? No,I’mjustputtingtheaddressthatwasrequestedinthere. It’sbeenalotoffunandIhavebeenlearninganawfullotwiththisCareerDevelopmentAwardandI’veappreciatedthechancetoreallyseehowhealthcareimpactsallofthesethingsinantimicrobialstewardship,eventhoughitseemslikeit’sbuttonedupalittlebit,andparticularfieldcaninfluencecareingeneralaswell. Ihavelearnedalotofmethods,alotofrespectforeverythingthatpeoplehavebeenteachingme. Myhopeis that I’llputsomemorethingsinthetoolkit. TheCDAhasmadeitpossibleformetogototheSantaFeInstitute’sComplexitySchoolnextmonth,soIhopetolearnalotmoreaboutnewanalyticmethods,sortofsystems thinking,systemapproaches. Morethingstocome.

Moderator:Thankyou.Wellwedidhaveafewpeoplewriteinsayingthankyoufortheexcellentpresentationandthat theyhavealottogetthroughontheslides.So weappreciateyou providingthatextrainfo.And,ofcourse,thankyoutoDr.RubinforjoiningusaswellandtoBarb Elspas.She’spartoftheCDAenhancementinitiativewhichsponsoredand organizedthismonthlysession.TheytakeplaceonthesecondTuesdayofeachmonthat1:00

p.m.Eastern,sopleasekeepaneyeonyouremailforanannouncementaboutnextmonth’s CDAsession.

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