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