HighlightsintheMedicineLiteraturefrom2016-2017:

Shouldanyresultschangeourpractice?

KellyEvans,MD

“Weareconstantlymisledbytheeasewithwhichourmindsfallintotherutsofoneortwoexperiences.”

“Nohumanbeingisconstitutedtoknowthetruth,thewholetruth,andnothingbutthetruth;andeventhebestofmenmustbecontentwithfragments,withpartialglimpses,neverthefullfruition.”

-SirWilliamOsler

Ihavenoconflictsofinteresttodisclose.

Objectives

• Deriveclinicalmeaningfrom3recentlypublishedarticles- RCTandotherdatatypes

• Discussthemeritsandflawsofeachtrial

• Decideifeachtrialismeaningfulenoughtoaffectorchangeone’scurrentpracticeinregardstotherelevantcondition

NEJM 2016375:16

Background

• Syncope…Ugh.

• CurrentAHAguidelinesforw/udonot includeguidanceforwhetherweshouldr/oPE

• Shouldnon-massivePEphysiologicallycausesyncope?

TheStudy

• Cross-sectionalstudytodetermineprevalence• Patientsenrolled2012-2014• Patients:Adultsadmittedto11Italianhospitalsforafirstepisodeofsyncope– NOT:Outpatients,patientsdischargedfromED,recurrent/previousepisodessyncope,ptsonanticoag,pregnantpts

TheStudy:Protocol

• PEruledoutorinwithin48hrs ofadmissioninalleligiblepatients

WellsScore<4(lowprob)

>4(highprob)

D-dimer*Negative– RULEDOUT

*Usedlabcutoffateachcenter(250-500mcg/ml)

Positive

CTPEorV/Qscan

Results

• 717admittedpatients;157excluded(onanticoag orrecurrentsyncope)à 560patientsenrolled

• Ofthe560patientsincluded,97(17.3%)hadpulmonaryembolismconfirmedwithimaging

Discussion

• CouldsomeofthesePE’sbeincidentalomas?

• Isthereagoodpathophysiologicexplanationfornon-massivePEcausingcerebralhypoperfusion?

• Shouldwechangeourpractice???

AnnalsofInternalMedicine3May2016

Background

• QuittingsmokingisHARD

• 6monthquitratesinclinicaltrials

Placebo 10-12%

Nicotine replacementtherapy 17-20%

Bupropion 14-20%

Varenicline 21-28%Cahilletal.JAMA 2014311:193

TheStudyRandomizationtoabruptorgradualcessation(spouseswerepairedinrandomization)

Patientsaskedtosetaquitday2weeksoutGradual: askedtohalvesmokingweek1,

quarterweek2Abrupt:Noreductionpriortoquitdate

NRT:Gradualgotpatches+ short-actingpriortoquitdate;Abruptjustpatchesprior;Bothgotpatches+short-actingafterQD

Bothgotbehavioralsupportfrom2weekspriorto8weeksafterquitdate

Primaryoutcome: 4-weekabstinence(ITT)Secondary:8-weekand6-monthabstinence*AllvalidatedbyexhaledCO

Exclusioncrit:CurrentcessationtxContraind toNRT

Nodifferenceingroups Medianage:4950/50M/F93%white35-38%livedwithsmokerMediancigs/day:20Confidenceinquitting:4(scale1-6)

Results

Abstinencerates:

Abruptcessation

Gradualcessation

4weeks:

49%

39%

8weeks:

36%

29%

6months:

22%

15%

NNT:10(4weeks);14(6months)

Discussion

• Whatdoyoutellyourpatients?Isthissurprisingtoyou?

• Physiologicorpsychologicexplanation?

• Shouldthisstudychangeourpractice?

NEJM 2017376;23

Background:SepsisandProtocols(EGDT)

Doearlygoal-directedtherapyprotocolsmakeadifference?

• Riversetall2001:YES!

• PROCESS2014:Nope.

TheStudy:Background

• AllNYhospitalsrequiredsepsisprotocols,includinga3-hrbundle– Bloodculturepriortoabx– Serumlactatemeasurement– Administrationofbroad-spectrumabx

• Anda6-hrbundle– 30cc/kgbolusIVFifhypotensionorlactate>4– Vasopressorsforrefractoryhypotension– Remeasurement ofserumlactate

TheStudy• Retrospectivestudyincludingpatient-leveldatafrom185NYhospitals(2014-2016)

• Patientsage>17;clinicallydefinedseveresepsisorsepticshock(accordingtoSepsis-22001)

• PatientshadprotocolinitiatedinED(ignoredhospital-acquiredsepsis)

• Excludedpatients:– 3-hrbundletook>12hours– Advancedirectiveslimitingtreatmentordeclinedtx– Hospitalswithfewerthan50casesofsepsis

TheStudy

• Primaryoutcome:In-hospitalmortality• Primaryexposure:Timetocompletionof3-hrbundle

• Risk-adjustmentmodeltodetermineassociationbetweenexposureandmortality– Bivariate(yes/nocompletionin3hrs)andcontinuousanalyses

Medianage7367%White

Admittedfrom:Home67%SNF27%

Siteofinfection:40%Respiratory27%Urinary

Results82%ofpatientshad3-hrbundlecompletedwithin3hrs- Mediantime1.3hrs

Inprimaryanalysis(topgraph),eachhouroftimetocompletionof3-hrbundlewasassociatedwithhighermortality- OR1.04perhr (95%CI1.02-1.05)- P<0.001

Comparingptswhohadcompletion3-12hrsto<3hrs,mortalityOR1.14(95%CI1.07-1.21,P<0.001)

3-hrbundle

Abx

IVFbolus

Results

82%ofpatientshad3-hrbundlecompletedwithin3hrs- Mediantime1.3hrs

Nodifferencesincharacteristicofptsinwhomcompletedwithin3hrs andthoseinwhomcompletedbetween3-12hrs

Inprimaryanalysis(topgraph),eachhouroftimetocompletionof3-hrbundlewasassociatedwithhighermortality- OR1.04perhr (95%CI1.02-1.05)- P<0.001

Comparingptswhohadcompletion3-12hrsto<3hrs,mortalityOR1.14(95%CI1.07-1.21,P<0.001)

Results

• “Ourresultswouldberobustunlessanunmeasuredconfounderwasatleasttwiceasprevalentamongptswhohadthe3-hrbundlecompleted1hr later”

• Hospitalswithhigherrateofbundlecompletionwithin3hrs – morelikelytobesmaller,lesslikelyteachinghospitals

Discussion• Conflictingdataintheliterature– ThisoneNOTaRCT- confounding?

• “AnalysisoftimetocompletionofIVFbolusismostpronetoconfoundingbyindication”

• Downsidestoearlyadminofbroadspectrumabx?

• ArecertainelementsofEGDT/bundlesmoreimportantthanothers?– Recall,Rivers protocolincludedScvO2monitoring,PRBCtransfusion,inotropes)

OneSlideSummaries

• Reviewofstudiesinvestigatingmethodsandoutcomesofreduction/discontinuationofLTOT

• 67studiesmetcriteria(11RCT’s;only5studiesinprimarycaresettings)– Only3metUSPSTFcriteriaforgoodquality,13fair;reviewfocusedonthese16

Annals 2017167(3)

Conclusions:• Findingssuggestthatpain,function,QOLmayimprove during/afteropioiddosereduction

Caveats:• Maybereversecausation?• Moststudiesincludedwillingparticipants

Annals 2017167(3)

• RCTlookingatO2 vsnoO2 forpatientswithCOPDandrestingsats of89-93%

• Foundnodifferenceintimetodeathorhospitalization,rateofhospitalization,exacerbations,orothermeasures

NEJM 2016375;17

• Retrospectivecohortofpts(n=28,266)withEMRdoc’d ARtostatin(15-20%hadCAD/strokehistory)

• ComparedCVoutcomes/deathinpatientswhohadstatincontinued/reinitiatedvsthosewhodidn’t.

• 70%didhavereinitiated/continuedstatinrx• MI/stroke/deathoccurredin12.2%ofptswhohadcontinuedstatin,13.9%ofthosewhodidn’t

• NNT=59

Annals 2017167(4)

Finalthoughts?

Thanks!