PopulationResearch

MarionRowlandMBPHD

Structureoftalks

Today

Somedefinitionsanddifferences

ClassicStudies

Amodernexampleofwhyweneedanunderstandingofepidemiology

Tomorrow

Studydesignandmethodology

VariousTerminologies

• PopulationHealth

• PublicHeath

• Epidemiology– Historically

• InfectiousDisease

• ChronicDisease

– ModernEpidemiology• ClinicalEpidemiology

• GeneticEpidemiology

ThePractitioners

Epidemiologist‐DollSusserSteinDawbar

Statistician‐HillMantelBerksonFisher

DefinitionofEpidemiology

Themainfunctionofepidemiologyistodiscovergroupsinthepopulationwithhighratesofdiseaseandwithlowratessothatthecauseofthediseasecanbepostulated

Morris1955

Epidemiologyisthestudyofcausality

Diseasedistributioninapopulation

Determinantsorriskfactorsofdisease

–Who–Why–When–How

Whatdowedo

ResearchMethodology

Person/patient/participant

Community/generalpopulation/clinicalsetting

Representativesampleandapplyfindingstothegeneralpopulation

DataSources

Publicallyavailabledatasets

Collectionofgroupspecificdata

LargeScalepopulationbasedstudies

IssuesinEpidemiology

CaseDefinitionDefinitionofSwineflu/avianflu/coldDefinitionofObesity/HypertensionDefinitionoflungcancer

WhoreportsSelfreportDoctorDiagnosedDefinitiveclinicaltest–Publicrecord

RegisterofdeathsCancerRegistriesNotifiablediseases

OnsetofDisease

Differentissuesindifferenttypesofdisease

InfectiousDiseaseChronicDisease/Cancer InductionPeriod

LatentPhaseofDiseaseDiagnosis

ScreeningClinicalDiagnosis

IncidentorPrevalentcases

OutcomeMeasure

Mortality

Bestoutcomemeasure

Morbidity

Somehardendpoint.

Measures

Statistics

Ratio

Percentage

Proportion

Probability

Definitions

Risk:Numberofpersonswhodevelopthediseaseduringfollow‐up

Numberofpersonsdiseasefreeatthestart

Rate:Numberofpersonswhodevelopthediseaseduringfollow‐up

Averagepopulationduringthestudyperiod

ProofofCausalityKockspostulates

Consistency

StrengthandDoseResponse

Specificity

Temporality

Biologicalplausibility

Reversibility

ClassicPopulationStudies

InfectiousDiseaseSirJohnSnow LondonCholeraEpidemic1948

ChronicDiseaseDollandHill SmokingandLungCancer1947

ThomasDawberFraminghamHeartStudies1948

NormativeDataHealthExaminationSurvey 1959

NationalHealthandNutritionalExaminationSurveys 1971

SmokingandLungCancer

DollandHill2

• SurveyofMedicalRegister(59,6000)inOct1951• Simple,short,Questionary• Smokingstatus:Current/Ex/Non‐smokersNumbersmoked• Responserate70%

• Outcomemeasure• RegisterofDeaths

• Results• DeathrateofheavysmokerswasX20thatofnon‐smokers• Increasingmortalitywithincreasingsmokingrates• Effectacrossallagegroups

DollandHillBMJ:19561071‐81

FraminghamStudies

• Framingham–towninMassachusetts

• Studybeganin1948–prospective/cohortstudy

• Enrolled5209participantswhohadnotyetdevelopedsymptomsofcardiovasculardisease

• Agegroup30–62years

• Physicalandlifestylefollow‐upevery2years

OtherFraminghamCohorts

OffspringCohort 1971

OmniCohort(506) 1994

ThirdGeneration 2002

NewOffspring/SpouseCohort 2003

SecondGenerationOmni 2003

RiskFactorsforCardiovascularDisease

IncreaseriskCigarettesmoking 1960Cholesterol,bloodpressure,andECGabnormalities 1961Obesity 1967Menopause 1976Menhavehigherriskthanwomen 1999HighNormalBloodpressure 2001

ReduceRiskPhysicalActivity 1967

HighBloodpressureincreasesriskofStroke 1970

Lessonsfromrecentepidemiologystudies

Helicobacterpyloricausespepticulcerdisease

Helicobacterpyloricausesgastriccancer

Newdata?

or

Didwereinventthewheel?

PepticUlcerDiseaseinthe1950s

Incidence‐2.3per100employees

10thmostcommoncauseofdeath

10%ofhospitaladmissions

SpiralOrganismsintheStomach

BarryMarshall

TheLancetJune4th1983Page1273‐5

Describedfirstcultureofgastricspiralorganisms

SpeculatedonassociationwithgastritisandPUD

RobinWarren

TheLancetJune4th1983Page1273

“theextraordinaryfeaturesofthesebacteriaisthattheyarealmostunknowntoclinicians”

Unansweredepidemiologicalquestions

1.Atwhatagedochildrenbecomeinfected?

2.WillchildrenbecomereinfectedwithH.pylorifollowingeradicationtreatment?

Reinfection

AgeGroup n Patientyearsoffollow‐up

Hpylori+ H.Pylori‐ Reinfectionrate/100PersonyearsUnder5years 6 6.75 4 2 59.2

Over5years 46 97.1 2 44 2.0

Total 52 103.8 6 46 4.8

Rowland et al Gastroenterology 1999

Conclusion

H.Pylorireinfectionoccursrarelyinolderchildren

Poorsocioeconomicconditionsnotariskfactorforreinfection

Havinginfectedparentsorsiblingsisnotariskfactorforreinfection

Youngeragemaybeariskfactorforreinfection

IncidenceofH.pyloriinfection

Requirements– Prospectivestudy

– Cohortofyoungnon‐infectedchildrenatriskofinfectionrequired

– Reasonablelengthoffollow‐up

– Lowsocio‐economicstatus

Enrolled 327 Families

Meanageatbaseline 33.25MonthsSD7.24

Range 23–48months

Female 45%

Age‐SpecificIncidenceofH.pylori

Rowland et al Gastroenterology 2006

MultivariateAnalysis

Factor UnivariateOddsRatio

95%CI MultivariateOddsRatio

95%CI

InfectedMother 5.4 2.4‐11.8 7.2 1.9‐26.3

InfectedSibling 7.3 3.5‐15.2 4.9 2.1‐11.5

>2bottles/day 1.89 0.96‐3.7 5.0 1.1‐21.8

Alwayssleepwithmother

1.89 0.96‐4.6 1.0 0.4‐2.5

Income<£8320/y 1.3‐4.8 1.3 0.6‐2.6

Rowland et al Gastroenterology 2006

HistoricalPerspectiveWheredidHelicobactercomefrom?

Spiralorganismsreportedongastricmucosafor>100yrs

AnimalsBizzozero 1893ArchfMikrBakt

Salomon 1896 CentralblfBakt

HumansKrienitz 1906 DtschmedWochenschrLuger 1917 WeinklinWochnschr

BacteriaandUlcerDiseaseStreptococcuswasaputativeorganism

NotculturedFailedtoinduceulcersinanimalmodels

Rosenow 1913JAMASaunders 1930ArchIntMedCeller 1916MedRecord

SpirochetesDoegens1939ArchPathFreedberg 1940AmJDigDis

1950s

Thetheoryofacidwasborn

Thetheoryofstressandurbanization

AND

TheoccasionaltheoryofinfectionwasunderminedFailuretofindspirochetesin1000biopsies

PalmerGastroenterology1954

Ureainthestomach

LuckandSethBiochemJ1924;18:1227‐31

Roleofgastricurease

FitzgeraldO,MurphyP.Nature;1948162:896

Urease

Antibiotictreatmentdecreasedammoniaandincreasedgastricacidity

LieberandLefevreJClinInvest1959;38:1271‐7

Gastricureaseactivityinmammalsisofbacterialorigin

DelluvaetalBiochemBiophysActa1968;151

SusserandSteinTheLancetSaturday20January1963

Yearofbirth

Cohorteffectandduodenalulcerdisease

100

DeathRatepe

rmillionliving

The1970s

Adventofendoscopyandelectronmicroscopy

Gramnegativespiralbacteriaongastricmucosaofallpatientswithgastritis

Steer1975JClinPath

Cultured“pseudomonasaeruginosa”SteerandColinJones1975

Gut

EndoscopyandelectronmicroscopystudyFung1979AmJGastroenterol

Question

WhydidBarryMarshallcultureH.pyloriandRobinSteerandothersfail?

TheResearchProcess

Researchisagig‐sawandeachpieceofinformationcontributestothepicture

Wemustacquaintourselveswithwhatisknownaboutourparticularareaofinterestinother

disciplines.

Wemustaskwhyandnotfollowblindly.