Dyspepsia Management in 2014

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  • GrigorisLeontiadis,MDPhDMcMasterUniversity

    UpperGastrointestinalandPancreaticDiseasesCochraneGroup

  • Norelevantfinancialrelationshipswithanycommercialinterests

  • CDDW/CASL Meeting Session: Dyspepsia management in 2014

    Medical Expert (as Medical Experts, physicians integrate all of the CanMEDS Roles, applying medical knowledge, clinical skills, and professional attitudes in their provision of patient-centered care. Medical Expert is the central physician Role in the CanMEDS framework.)

    Communicator (as Communicators, physicians effectively facilitate the doctor-patient relationship and the dynamic exchanges that occur before, during, and after the medical encounter.)

    Collaborator (as Collaborators, physicians effectively work within a healthcare team to achieve optimal patient care.)

    Manager (as Managers, physicians are integral participants in healthcare organizations, organizing sustainable practices, making decisions about allocating resources, and contributing to the effectiveness of the healthcare system.)

    Health Advocate (as Health Advocates, physicians responsibly use their expertise and influence to advance the health and well-being of individual patients, communities, and populations.)

    Scholar (as Scholars, physicians demonstrate a lifelong commitment to reflective learning, as well as the creation, dissemination, application and translation of medical knowledge.) Professional (as Professionals, physicians are committed to the health and well-being of individuals and society through ethical practice, profession-led regulation, and high personal standards of behaviour.)

    CanMEDS Roles Covered in this Session:

  • Agenda

    Uninvestigateddyspepsia; functionaldyspepsia

    definitions

    criticalappraisaloftreatments

    ofestablishedefficacy

    emerging,promising

    conclusions

  • Evolvingdefinition

    Misleadingetymology:twoancientGreekwords

    dys (bad,abnormal,difficult,impaired) pepsis (digestion)

    Dyspepsia

  • Oneormoreofthefollowing: epigastricpain epigastricburning postprandialfullness earlysatiation

    Itshouldnot becalleddyspepsiaifthepredominantsymptomsareheartburnoracidregurgitation

    Tacketal.Functionalgastroduodenaldisorders.In:RomeIII,2006

    RomeIIIdefinition

    Dyspepsia

  • Oneormoreofthefollowing: epigastricpain epigastricburning postprandialfullness earlysatiation

    andNoevidenceofstructuraldisease(includingatupperendoscopy)thatislikelytoexplainthesymptoms

    Tacketal.Functionalgastroduodenaldisorders.In:RomeIII,2006

    RomeIIIdefinition

    1.

    Functionaldyspepsia(FD)

    2.

    Criteria fulfilled for 3 months

    symptom onset 6 months prior to diagnosis

  • Burdenofdyspepsia

    Prevalenceofdyspepsia:2040% (Marwaha etal.DDW 2009)

    Incidence:1% peryear

    70%ofpatientswithdyspepsiahaveFD(Fordetal.Clin Gastr Hepatol 2010)

    Significantreductionofpatientsqualityoflife

    Significanteconomicburdentothehealthcaresystem

    CauseoffrustrationtophysiciansbecausenomedicationiscurrentlyapprovedintheUS,CanadaortheEUforthetreatmentofFD

    Lacyetal.AP&T 2013

  • Topthreestrategies:

    Promptendoscopy(andtreataccordingly)

    H. pyloritest(noninvasively)andtreat

    Initialacidsuppression(andscopethefailures)

    Early endo: more effective in curing dyspepsia, but more costly and not cost-effective

    No difference in efficacy or cost

    Fordetal.Gastroenterol 2005

    Fordetal.AP&T 2008

    Managementofuninvestigated dyspepsia

  • Clinicalpracticeguidelines

    NICE2004

    Canadian2005

    AGA2005

    ASGE 2007

    AsianPacific2012

    (Lacyetal.AP&T 2012)

    Managementofuninvestigated dyspepsia

  • Fails

    VanZanten etal.CanJGastroenterol 2005Talleyetal.Gastroenterol 2005

    Uninvestigateddyspepsia nootherobviouscauses age

  • Functionaldyspepsia

  • FDprobablyincludesmultipledifferententitieswithdistinctunderlyingpathophysiologies

    Ideally,thetherapeuticapproach shouldtarget theunderlyingpathophysiology

    However,ithasbeenverydifficulttoidentifyFDsubgroupsreliablybasedonsymptoms

    FDsubgroups

  • Causative agents

    Pathophysiological change Symptoms

    PathophysiologyofFD

  • Postprandialdistresssyndrome(PDS)

    Epigastricpainsyndrome(EPS)

    FDsubgroupsRomeIIIdefinitions

    may co-exist

  • Postprandialdistresssyndrome(PDS)

    Severaltimesaweek,oneorbothof:

    1.Bothersomepostprandialfullness,occurringafterordinarysizemeals

    2.Earlysatiationthatpreventsfinishingaregularmeal

    FDsubgroupsRomeIIIdefinitions

    Tacketal.Functionalgastroduodenaldisorders.In:RomeIII,2006

  • Epigastricpainsyndrome(EPS)

    Allofthefollowing:

    1.Painorburninglocalizedtotheepigastriumofatleastmoderateseverity,atleastonceperweek

    2.Intermittent

    3.Notgeneralizedorlocalizedtootherabdominalorchestregions

    4.Notrelievedbydefecationorpassageofflatus

    5.NotfulfillingthecriteriaforgallbladderorSODdisorders

    FDsubgroupsRomeIIIdefinitions

    Tacketal.Functionalgastroduodenaldisorders.In:RomeIII,2006

  • Proximatecausesofdyspepsia(microorganisms,foods,drugs,otherenvironmentalfactors,genes,combinationsoftheabove)

    Ultimatecausesofdyspepsia:Q:Doesdyspepsiaservethehumanspeciesinterest,andifso,how?A:possiblyyes;itisbeneficialforapopulation(itconfersasurvivaladvantage)tohave:

    1.awarningmechanismagainstlifethreateningbehaviours(somevariabilityamongindividualswouldbeinevitable)

    2.aproportionofindividualswithchronic,moderatedyspepsia.Why?

    Dyspepsiafromanevolutionaryperspective

  • ManagementoptionsforFD

    H.pylorieradicationtherapy probiotics dietarymodifications acidsuppression prokinetics antidepressants psychologicaltherapy antinociceptiveagents herbaltherapies acupuncture

  • HpylorieradicationtherapyinFD

    Systematicreview&metaanalysisof21RCTs Outcome:dyspepsiacureat3 12months Comparator: placebo,PPI,H2RA,prokinetic Results:

    RRforHpylorieradicationgroupvs.control:0.90 (95%CI0.860.94) NNT14 (95%CI10to25)

    Informallyupdated;resultshardlychanged:NNT13Moayyedi.ArchInternMed2011

    Moayyedietal.CochraneDat Syst Rev2006

  • HpylorieradicationtherapyinFD

    Systematicreview&metaanalysisof21RCTs Outcome:dyspepsiacureat3 12months Comparator: placebo,PPI,H2RA,prokinetic Results:

    RRforHpylorieradicationgroupvs.control:0.90 (95%CI0.860.94) NNT14 (95%CI10to25)

    Informallyupdated;resultshardlychanged:NNT13Moayyedi.ArchInternMed2011

    ThebeneficialeffectofHpylorieradicationRxappliesequallytoepigastricpainanddysmotilityFDsubgroups

    Moayyedietal.CochraneDat Syst Rev2006

    Suzuki&Moayyedi.NatRevGastroenterol 2013

  • HpylorieradicationtherapyinFD

    ItispossiblethattheantibioticsusedinHpylorieradicationtherapyaretreatingotherorganismsratherthanHpylori,andthisisthereasonfortheireffectinfunctionaldyspepsia

    Whatistheproportionofpatientswhowerecuredfromdyspepsiaafterunsuccessful Hpylori eradicationtreatment?

    Moayyedi.ArchInternMed2011

  • 103Hpylori+(ve)patients,scopedforvariousreasons(notallhadFD)

    43speciesofbacteriaculturedandisolatedfrom65%ofthepatients

    SeveralstudieshavesystematicallyexaminedtheroleofsmallbowelmicrobiotainIBS

    Nostudieshavesystematicallyexaminedtheroleofthemicrobiotaofthestomach,duodenalandproximaljejunuminFD

    NoRCTsontheefficacyofprobiotics inFD

    Hu etal.WorldJGastroenterol 2012

    GImicrobiota

  • GImicrobiota

  • EradicateifH.pylori(+)ve

    ManagementofFD

    Functionaldyspepsia

    All7CPGs publishedsince2009agreeonthisapproach Thebenefitissmall(NNT14),but

    theeffectislongterm H.pylorieradicationhasadditionalbenefits(preventionofPUD,

    esp.complicatedPUD,possiblypreventionofgastriccancer)Suzuki&Moayyedi.NatRevGastroenterol 2013

    WhatifthisapproachfailstocureFD?

  • WhichfoodsshouldIavoid,doctor?

    DietinFD

  • DietinFD

    Ninestudieshaveassesseddietarypatterns/eatingbehaviorinFD Inconsistentresults(exceptwithfattyfoods) Patientsidentifyspecificfoodsastriggersoftheirsymptoms,

    butblindchallengetestsprovideinconsistentresults Possiblecognitivefactors

    (anticipationduetopreviousnegativeexperiencewithcertainfoods)

    NostudieshaveassessedtheefficacyoftargeteddietaryinterventionsinFD IstherearoleforGFDorlowFODMAPdietforFD? Shouldalldyspepticsbetestedforceliacdiseaseornonceliacgluten

    sensitivity?

    FeinleBisset &Azpiroz.NatRevGastroenterol 2013

  • Probablyreasonablesuggestions(but,verylowqualityofevidence):

    smallermeals(?betterchewing,slowereating)

    reducedfatintake

    ?dietcalendar?

    relatedlifestylemodifications reduce/modifyalcoholconsumption stopsmoking(tobacco,marihuana)

    Ford&Moayyedi.BMJ 2013Lacyetal.AP&T 2012

    Diet(andlifestyle)inFD

  • AcidsuppressioninFD

    ACochraneSR&MA:

    Antacids vs.placebo(1RCT):nodifference

    H2RAs vs.placebo(12RCTs):RRR 23%(95%CI8%to35%);NNT=7 unexplainedheterogeneity publicationbias

    PPIs vs.placebo(10RCTs):RRR 13%(95%CI4%to20%);NNT=10 unexplainedheterogeneity

    Moayyedietal.CochraneDat Syst Rev2006

  • PPIsinFD

    SR&MAandeconomicanalysis(USsetting):

    DifferentefficacyaccordingtoFD dyspepsiasubgroup

    Moayyedietal.Gastroenterol 2004

  • ProkineticsinFD

    Logicalchoice...

    2006Cochranereviewof24RCTs(beingupdatedcurrently)

    MostoftheRCTsusedcisapride

    Cisapridewithdrawn

    Unexplainedheterogeneity,likelypublicationbias,noeffectseeninhighqu