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APPLIED EPIDEMIOLOGY
Prepared by
Antonio E. Chan, M.D.
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1. Define epidemiology and outline its scope
2. Differentiate epidemiology from clinicalepidemiology
3. Describe approaches to establishingnormality
4. Describe criteria and measures of disease
occurrence commonly used inepidemiology
5. Enumerate some routinely available datause in epidemiology
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Learningobjectives
6. Understanddiagnostictestinrelationtodisease
7. Describethemaintypesofepidemiologicalstudies
8. Enumeratetheadvantagesanddisadvantagesofobservationalstudiescomparedwithexperimentalstudies
9. Explaincauseofdisease
10. Outlinethestepsnecessarytoestablishthecauseofdisease
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Learningobjectives
11. Appreciate the differing approaches usedin epidemiology to compare theoccurrence of disease
12. Outlinetheroleofepidemiologyindescribingthenaturalhistoryofadiseaseandprognosis
13. Understandtheroleofepidemiologyinthe
preventionandcontrolofdiseasethroughidentificationofthecausesofdisease
14. Relatethedifferentstagesofthedevelopmentofadiseasetothephasesofprevention
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WhatisEpidemiology?
The study of the distribution and
determinants of health-related states
or events in specified populations, and
the application of this study to controlof health problems
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Tounderstandthecourseofthe
disease(naturalhistoryofthedisease) Toidentifythecausesorriskfactors
Toprovideeffectivemeasuresof
treatmentandprevention
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Uses of epidemiologyGenetic factors
1. Causation
Environmental factors(including lifestyle)
2. Natural history
3. Description of health statusof population
Proportion with ill health,change over time,
change with age, etc
Good health Ill health
Good health Subclinicalchanges
Clinicaldisease
Death
Recovery
Good health
ILLhealth
Time
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Uses of epidemiology
4. Evaluation ofintervention Good health Ill health
TreatmentMedical care
Health promotionPreventive measuresPublic health services
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APPLIEDEPIDEMIOLOGY
Clinicalepidemiology
Communicablediseaseepidemiology
Environmentalandoccupationalepidemiology
Molecularepidemiology
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CLINICALEPIDEMIOLOGY
Definition
istheapplicationofepidemiologicalprinciplesand
methodstothepracticeofclinicalmedicine
isthescienceofmakingpredictionsaboutindividual
patientsbycountingclinicaleventsinsimilar
patients,usingscientificmethodsforstudiesofgroupsofpatientstoensurethatthepredictionsare
accurate
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CLINICAL EPIDEMIOLOGY
Purpose:
todevelopandapplymethodsofclinicalobservationsthatwillleadtovalid
conclusionsbyavoidingbeingmisledby
systematicerrorandchance
tomakegooddecisionsinthecareofpatients
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TheRelationshipBetween
EPIDEMIOLOGY+ CLINICALMEDICINE
Populations Individuals
Studies/Assessments
Prevention
EvaluationPlanning
Diagnosis
Treatment
Curing
Caring
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ClinicalQuestion
IssueQuestion
Abnormality Isthepatientsickorwell?
Diagnosis Howaccuratearetestsusedtodiagnosedisease?
Frequency Howoftendoesadiseaseoccur?
Risk Whatfactorsareassociatedwithanincreasedriskofdisease?Prognosis Whataretheconsequencesofhavingadisease?
Treatment Howdoestreatmentchangethecourseofdisease?
Prevention Doesaninterventiononwellpeoplekeepdiseasefromarising?
Doesearlydetectionandtreatmentimprovethecourseof
disease?
Cause Whatconditionsleadtodisease?Whatarethepathogenetic
mechanismsofdisease
Cost Howmuchwillcareforanillnesscost?
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Sourcesofdatausefulfor
epidemiologystudies
Data on vital events birth and death
Morbidity or disease statistics
Data on physiologic and or pathologiccondition
Statistics on health resources and services
Statistics pertaining to the environment Demographic data
Socio-cultural data
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MeasuringHealthandDiseaseClinicalquestion:Isthepatientsickorwell?
Healthisdefinedasastateofcomplete
physical,mental,andsocialwell-being
andnotmerelytheabsenceofdiseaseorinfirmity.
Epidemiologistsdefinitionofhealthstates diseasepresentordiseaseabsent
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MeasuringHealthandDiseaseClinicalquestion:Isthepatientsickorwell?
Diagnostictests
qualitativediagnostictest
quantitativediagnostictestNormal(Gaussian)distributionmethod
Percentilemethod
TherapeuticmethodPredictivevaluemethod
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MeasuringHealthandDisease
Diagnostic criteria are usually based on
symptoms, signs and test results
1. Hepatitis presence of antibodies in the blood
2. Asbestosis - symptoms and signs of specific changes
in lung function,
- radiographic demonstration of fibrosis of
the lung tissue or pleural thickening and
- history of exposure to asbestos fibers.
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Major Manifestations Minor ManifestationsCarditisClinical:
PolyarthritisfeverChoreaathralgia(jointpains)
Erythemamarginatumpreviousrheumaticfeveror
Subcutaneousnodulesrheumaticheartdisease
Laboratory:
Acutephasereactants:
AbnormalESR,CRP,
leukocytosis
ProlongedP-Rinterval
TheJonesCriteria(revised)forGuidanceinthe
DiagnosisofAcuteRheumaticFever
Ahighprobabilityofrheumaticfeverisindicatedbythepresenceoftwomajor
oronemajorandtwominor,manifestations,ifsupportedbyevidenceofa
precedingGroupAstreptococcalinfection
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MAJORSIGNS MINORSIGNS
Weightloss>10%Persistentcough>1month
Fever>1month GeneralpruriticdermatitisChronicdiarrhea>1monthRecurrentherpeszoster
Generallymphadenopathy
Chronicherpessimplex
Oralcandidiasis
WHOCASE-DEFINITIONFORAIDS
ThepresenceofdisseminatedKaposissarcomaor
cryptococcalmeningitis
or
Twomajorsignsinassociationwithatleastoneminorsign
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MeasuringHealthandDisease
Diagnosticcriteriamustbeclearlystated,easytouseandeasytomeasureinastandardmannerunderawidevarietyofcircumstancesbydifferentpeople
Diagnosticcriteriamaychangequiterapidlyasknowledgeortechniquesimprove.
Definitionsusedinclinicalpracticearelessrigidlyspecifiedandclinicaljudgmentismoreimportantindiagnosis
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MeasuringHealthandDisease
The development of criteria to establishthe presence of disease requires
definition of normality and abnormality
Difficult to define what is normal
No clear distinction between normal andabnormal
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ApproachesinestablishingnormalityClinicalquestion:Isthepatientsickorwell?
Problem(misclassification)
Clinicalmeasurements
nominalasymptomatic
ordinalcut-offpointintervalorratio
Clinicalmeasurementshaveskeweddistributions
Percentilemethod(sameprevalencerates)
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Levelatwhichtreatmentdoesmoregoodthanharm-Cost
Inspecificagegroupsformenandwomenatwhichtreatmentmakes
economicaswellasmedicalsense
Criteriachangefromtimetotime
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ApproachesinestablishingnormalityClinicalquestion:Isthepatientsickorwell?
Normal Abnormal
commonorusualbeingunusual
well beingsick
notbeingtreatablebeingtreatable
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MeasuresofdiseasefrequencyClinicalquestion:Howoftendoesadiseaseoccur?
Prevalenceofadiseaseisthenumberofcasesinadefinedpopulationataspecifiedpointintime
Pointprevalence
Periodprevalence
Incidenceisthenumberofnewcasesarisingina
givenperiodinaspecifiedpopulation
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MeasuringdiseasefrequencyClinicalquestion:Howoftendoesadiseaseoccur?
Theprevalencerate(P)foradiseaseiscalculatedas
follows:
Numberofpeoplewiththediseaseorcondition
P=-----------------------------------------------------------------(xfactor)
Numberofpeopleinthepopulationatriskatthe
specifiedtime
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MeasuringdiseasefrequencyClinicalquestion:Howoftendoesadiseaseoccur?
Incidencerate(I)
Numberofpeoplewhogeta
diseaseinaspecifiedperiodI=----------------------------------------------------X(factor)
Sumofthelengthoftimeduringwhich
eachpersoninthepopulationisatrisk
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MeasuringdiseasefrequencyClinicalquestion:Howoftendoesadiseaseoccur?
Incidencerate
Thenumeratoristhenumberofnewevents
thatoccurinadefinedtimeperiod Thedenominatoristhepopulationatriskof
experiencingtheeventduringthisperiod
Themostaccuratewayofcalculating
incidencerateistocalculatetheperson-
timeincidencerate(Incidencedensity)
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MeasuringdiseasefrequencyClinicalquestion:Howoftendoesadiseaseoccur?
Cumulativeincidencerateorrisk(CI)
Numberofpeoplewhogetadiseaseduringaspecifiedperiod
CI=----------------------------------------------------X(factor)
Numberofpeoplefreeofthediseasein
thepopulationatriskatthebeginningoftheperiod
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Factorsinfluencingobservedprevalencerate
Increasedby:Decreasedby:
LongerdurationofthediseaseShorterdurationofdisease
ProlongationoflifeofpatientHighcase-fatalityratefromdisease
withoutcure
IncreaseinnewcaseDecreaseinnewcases
(increaseinincidence)(decreaseinincidence)
In-migrationofcasesIn-migrationofhealthypeople
Out-migrationofhealthypeopleOut-migrationofcases
In-migrationofsusceptiblepeopleImprovedcurerateofcases
Improveddiagnosticfacilities
(betterreporting)
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MeasuringdiseasefrequencyClinicalquestion:Howoftendoesadiseaseoccur?
Prevalencestudiesdonotusuallyprovidestrongevidenceofcausality
Itishelpfulinassessingtheneedforhealthcareandtheplanningofhealthservices
Prevalenceratesareoftenusedtomeasuretheoccurrenceofconditionsforwhichtheonsetofdiseasemaybegradual
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MeasuringdiseasefrequencyClinicalquestion:Howoftendoesadiseaseoccur?
Cumulativeincidencerate
Unlikeincidencerate,itmeasuresthedenominatoronlyatthe
beginningofastudy
Thisratehasasimplicitythatmakesitsuitableforthe
communicationofhealthinformationtodecisionmakers
Easytointerpretandprovideausefulsummarymeasure
Itisusefulapproximationofincidenceratewhentherateis
loworwhenthestudyperiodisshort
E l
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274
CI=------------x1000=2.3per1000
118,539
Example
Relationshipbetweencigarettesmokingandincidencerate
Strokeinacohortof118,539women
Neversmoked 70395,59417.7
Ex-smoker65232,71227.9
Smoker139280,14149.6
Total274908,44730.2
Person-yearsStrokeincidencerate
SmokingNo.ofcasesofobservation(per100,000
Categoryofstroke(over8years)person-years)
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Measuringdiseasefrequency
Clinicalquestion:Howoftendoesadiseaseoccur?
Case-fatalityrate
ameasureoftheseverityofadisease
No.ofdeathsfromadiseaseinaspecifiedperiod
Casefatalityrate=------------------------------------------X100
(CFR)No.ofdiagnosedcasesofthe
diseaseinthesameperiod
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USEOFAVAILABLEINFORMATION
(Mortality)
Numberofdeathsinaspecifiedperiod
Crudemortalityrate=---------------------------------------------------------XF
(CMR)Averagetotalpopulationduringthatperiod
Thismortalitycanbemadespecificastoage,sexorcause
Notappropriatetouseforcomparisonbecausedeathvaries
accordingage,sex,race,socio-economicclassandotherfactors
Comparisonofmortalityratesbetweengroupsofdiverseage
structureareusuallybasedonage-standardizedrates
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Standardizationofrates
(Adjustmentofrates)
1.Directadjustmentofrates
Thisrequirestheselectionofsomepopulation,calledastandardpopulation,towhichtheage-specificratesforeachpopulation
canbeapplied.
2.Indirectadjustmentofrates
Standardizationisbasedonage-specificratesratherthanagecomposition
Thepopulationwhoseratesformthebasisforcomparisonis
referredtoasthestandardpopulation
Thelargerofthetwopopulationsisusuallychosenasstandard
becauseitsratestendtobemorestable
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Standardizationofrates
(Adjustmentofrates)
Ifdevelopedandanundevelopedcountryarecompared,the
developedcountrywouldprobablybetakenasthestandard
Acommonwayofcarryingoutindirectage-adjustmentistorelatethetotalexpecteddeathsthusobtainedtoobserved
deathsthroughaformulaknownastheStandardizedMortality
Ratio(SMR)
Totalobserveddeathsinapopulation SMR=-------------------------------------------------------
Totalexpecteddeathsinthatpopulation
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Standardizationofrates
(Adjustmentofrates)
Interpretation:
Ifthismortalityratioisgreaterthan1,itmeansthatmoredeaths
areobservedinthesmallerorcomparisonpopulationthanwouldbeexpectedonthebasisofratesinthelarger
(standard)population
Iftheratioislessthan1,fewerdeathsareobservedthan
expected
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Example:Directmethod
Comparisonofdeathratesintwopopulationsbyage
AnnualAnnualAge-specificNumberCrude
AgePopulationDeathrateofDeathrate
(years)NumberProportion(per1000)Deaths(per1000)
(1)(2) (3) (4)(5)(6)PopulationA
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ComputationofExpectedNumberofDeathsbyDirectMethod
Example1:IdenticalAge-specificRates
PopulationAPopulationBAge-specificAge-specific
AgeStandardPopulationDeathRateExpectedDeathRateExpected
(years)(AandBCombined)per1000Deathsper1000Deaths
(1)(2)(3)=(2)x(1)(4)(5)=(4)x(1)
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ComputationofExpectedNumberofDeathsbyDirectMethodExample2:DifferentAge-specificRates
PopulationAPopulationBAge-specificAge-specific
AgeStandardPopulationDeathRateExpectedDeathRateExpected
(years)(AandBCombined)per1000Deathsper1000Deaths
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p
DeathsbyAgeandPhotofluorogramReading(Whites)for
Three-and-a-HalfYearObservationPeriod,
MuscogeeCounty,Georgia,1946
NegativeforCardiovascularDiseaseSuspectforCardiovascularAge-specificDiseaseAgein1946NumberofdeathratesNumberof
(years)Population Deathsper100 PopulationDeaths
153413,681350.25231
35548,8381021.15245
55andover2,2531496.616514
-----------------------------
Allages24,77228611220
Crudedeathrateper1001.1517.9
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PercentageDistributionbyAgeofNegativesandSuspects,
MuscogeeCounty,Georgia
1534 13,681 55.2 23 20.5
35548,838 35.7 24 21.4
55andover2,253 9.1 65 58.0
Allages24,772100.0112 99.9
NegativeforSuspectfor
CardiovascularDiseaseCardiovascularDisease
AgePercentagePercentage
(years)NumberofPopulationNumberofPopulation
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CalculationofStandardizedMortalityRatiofor
SuspectsComparedwithNegatives,
MuscogeeCounty,Georgia
(1) (2)(3)=(1)x(2) (4)
153423 0.25 .1 1
3554 24 1.15 .3 5
55andover 65 6.61 4.3 14
Allages4.720
DeathRatesper100ExpectedDeathsObserved
forPersonsNegativeamongSuspectsDeaths
AgeNumberofforCardiovascularAccordingtoRatesamong
(years)SuspectsDiseaseforNegativesSuspects
Observeddeaths20
SMR=--------------------------=---------=4.25
Expecteddeaths4.7
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No.ofdeathsinayearofchildrenlessthan1yearofage
Infantmortalityrate=------------------------------------------------------XF
No.oflivebirthsinthesameyear
Ameasureofoverallhealthstatusforagivenpopulation
Itisbasedontheassumptionthatitisparticularlysensitiveto
socio-economicchangesandtohealthcareintervention
Othermeasuresofmortalityinearlychildhoodare:
1.Fetaldeathrate 2.Stillbirthorlatefetaldeathrate
3.Perinatalmortalityrate
4.Neonatalmortalityrate
5.Postneonatalmortalityrate
Mortality
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Child mortality rate
is based on deaths of children aged 1 4 years and is importantbecause accidental injuries, malnutrition and infectious diseases
are common in this age group
Maternal pregnancy-relateddeaths in a year
Maternal mortality rate = -------------------------------------
Total births in the same year
Life expectancyis the average number of years an individual of agiven age is expected to live if current mortality rates continue
Mortality
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LifeExpectancy(years)atselectedages
forfourcountries
Age Mauritius Bulgaria USA Japan
Birth65.068.371.675.8
45years25.327.330.432.9
65years11.712.615.016.2
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DIAGNOSISClinicalquestion:Howaccuratearetestsusedtodiagnosedisease?
Diagnostictesttheobjectiveistodiagnoseanytreatable
diseasepresent
Characteristicsofadiagnostictest
Reliablegivesthesamemeasurementwhenrepeatedmorethanonce
Valid-measureswhatitintendstomeasure
AccuratecorrectlydeterminesthosewithdiseaseandthosewithoutEasytousecanbeperformedbyotherpeoplewithoutdifficulty
Notexpensiveaffordable
Safeandacceptable
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Goldstandard
asounderindicationoftruthorastandardof
accuracy
-anewdiagnostictestiscompared
-elusive(notavailable)
-expensiveandriskybiopsy,surgicalexploration,
autopsy-sometimessimplethroatswabculture
DIAGNOSISClinicalquestion:Howaccuratearetestsusedtodiagnosedisease?
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80 90 100 110 120 130 140 150 160 170
Normal Group Abnormal Group
B l o o d L e v e l ( mg / 100 ml )
Cut-offpoints
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DIAGNOSISClinicalquestion:Howaccuratearetestsusedtodiagnosedisease?
V lidit f di ti t t
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Validityofadiagnostictest
a=no.oftruepositives,b=no.offalsepositives
c=no.offalsenegatives,d=no.oftruenegativesSensitivity=probabilityofapositivetestin
peoplewiththedisease
=a/(a+c)
Specificity=probabilityofanegativetestinpeoplewithoutthedisease
Positivepredictivevalue=probabilityofthepersonhaving
thediseasewhenthetest
ispositive
=a/(a+b)Negativepredictivevalue=probabilityofthepersonnot
havingthediseasewhenthe
testisnegative
=d/(c+d)
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DISEASEClinicalquestion:Howaccurateareteststodiagnosedisease?
Paralleltests(allatonce)-usedwhenrapidassessmentisnecessaryasinhospitalizedoremergencypatients,orforambulatorypatientswhocannotreturneasilyforevaluationbecausetheyhavecomefroma
longdistance
- Paralleltestsgenerallyincreasethesensitivityand,therefore,thenegativepredictivevalueforagivendiseaseprevalenceabovethoseofeachindividualtest.Ontheotherhand,
specificityandpositivepredictivevaluearelowered
- Paralleltestingisusefulwhentheclinicianisfacedwiththeneedforaverysensitivetestbuthasavailableonlytwoormorerelativelyinsensitiveones.
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DISEASEClinicalquestion:Howaccurateareteststodiagnosedisease?
Serialtesting(consecutively,basedonprevioustest
result)
-usedwhenrapidassessmentisnotrequired
-usedwhensomeofthetestsareexpensiveorrisky
-maximizesspecificityandpositivepredictivevalue
butlowerssensitivityandthenegativepredictive
value.
-theprocessismoreefficientifthetestwiththe
highestspecificityisusedfirst.
EffectofSequenceisSerialTesting:AThenBversusBThenA
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q g
Prevalence of DiseaseNumber of patients tested 1000Number of patients with disease 200 (20% prevalence)
Sensitivity and Specificity of the Tests
Test Sensitivity SpecificityA 80 90B 90 80
Sequence of Testing
Begin with Test A Begin with Test BDisease Disease+ - + -
A + 160 80 240 B + 180 160 340- 40 720 760 - 20 640 660
200 800 1000 200 800 1000
240 Patients Retested with B 340 Patients Retested with ADisease Disease+ - + -
B + 144 16 160 A + 144 16 160- 16 64 80 - 46 144 180
160 80 240 180 160 340
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DISEASEClinicalquestion:Howaccuratearetestsusedtodiagnosedisease?
Statementsaboutvaliditytest
Sensitivityandspecificityareinverselyrelated.
Asensitivetestcanpickupmostcasesofthediseasebutit
willerroneouslylabelaspositivemanypersonswhodonot
havethedisease.
Ahighlyspecifictestwillcorrectlylabelasnegativethose
whodonothavethediseasebutitwillmissmanycases.
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Trade-OffbetweenSensitivityandSpecificitywhenDiagnosingDiabetes
BloodSugarLevel
2hrafterEating Sensitivity Specificity
(mg/100mL) (%) (%)
7098.6 8.8
80 97.1 25.5
90 94.3 47.6
100 88.6 69.8
110 85.7 84.1120 71.4 92.5
130 64.3 96.9
140 57.1 99.4
15050.0 99.6
16047.1 99.817042.9 100.0
180 38.6 100.0
19034.3 100.0
20027.1 100.0
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DISEASEClinicalquestion:Howaccurateareteststodiagnosedisease?
Averysensitivetestgivesalowpositivepredictivevaluesince
itproducesmanyfalsepositive.Conversely,averyspecific
testgivesahighpositivepredictivevalue.
Sensitivityandspecificityareunaffectedbytheprevalenceof
thediseaseorcondition.Sincesensitivitydependsonlyon
thosewiththediseaseorconditionandspecificityonlyon
thosewithoutthediseaseorcondition.
Thepositivepredictivevalueofatestincreaseswiththe
prevalenceofthedisease.
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DISEASEClinicalquestion:Howaccurateareteststodiagnosedisease?
Usesofsensitivetests
Asensitivetestshouldbechosenwhenthereisanimportantpenaltyformissingadisease(dangerousbuttreatable
condition)
Asensitivetestismosthelpfultotheclinicianwhenthetest
resultisnegative(toruleoutdisease)
Usesofspecifictests
Highlyspecifictestsareneededwhenfalse-positiveresultscanharmthepatientphysically,emotionally,orfinancially.
Aspecifictestismosthelpfulwhenthetestresultispositive
(toconfirmorruleinthedisease
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DISEASEClinicalquestion:Howaccurateareteststodiagnosedisease?
Problems:
Lackofinformationonnegativetests
Lackofinformationontestresultsinthe
nondiseased
Lackofobjectivestandardsfordisease
Consequencesofimperfectstandards
Ifanewtestiscomparedwithanold(butinaccurate)standardtest,thenewtestmayseemworseevenwhenitisactuallybetter
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DISEASEClinicalquestion:Howaccurateareteststodiagnosedisease?
Reliabilityandvalidity
Measurementerror
InstrumentThemeansofmakingthemeasurement
ObserverThepersonmakingthemeasurement
Biologicvariation
WithinindividualsChangesinpeoplewithtimeandsituation
AmongindividualsBiologicdifferencesfrompersontoperson
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DISEASEClinicalquestion:Howaccurateareteststodiagnosedisease?
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Typesofepidemiologicalstudy
Type of study Alternative name Unit of study
Observational studies
Descriptive studies
Analytical studies
Ecological Correlational PopulationCross-sectional Prevalence Individuals
Case-control Case-reference Individuals
Cohort Follow-up Individuals
Experimental studies Interventional studiesRandomized controlled trials Clinical trials Patients
Field trials Healthy people
Community trials Community intervention Communities
studies
Types of epidemiological study
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Typesofepidemiologicalstudy(Descriptivestudies)
Casereports
-detailedpresentationsofasinglecaseorahandfulofcases
-meansofdescribingrareclinicalevents
-describeunusualmanifestationsofdisease
-elucidatethemechanismsofdiseaseandtreatment
-placeissuesbeforemedicalcommunityandoftentrigger
moredecisivestudies
-susceptibletobias
Types of epidemiological study
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Typesofepidemiologicalstudy(Descriptivestudies)
Case-series
-asimpledescriptiveaccountofinterestingcharacteristics
observedinagroupofpatients
-studylargergroupofpatients(e.g.10ormore)withparticular
disease
-describetheclinicalmanifestationsofdiseaseandtreatments
inagroupofpatientsassembledatonepointintime
-absenceofacomparisongroup,notconclusive
-hypothesis-generating
-selectionbias
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Typesofepidemiologicalstudy(Observationalstudies)
Ecologicalstudies
-aggregateriskstudies
-unitsofanalysisarepopulationsorgroupsofpeoplerather
thanindividuals
-relyondatacollectedforotherpurposes;dataondifferent
exposuresandonsocioeconomicfactorsmaynotbeavailable
-ecologicalfallacy(bias)
-usefulinraisinghypothesis
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Typesofepidemiologicalstudy(Observationalstudies)
Cross-sectionalStudy(PrevalenceStudy)
Typesofepidemiologicalstudy
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Observationalstudies
Cross-sectional(Prevalencestudy)
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Typesofepidemiologicalstudy(ObservationalStudies)
-measuretheprevalenceofdisease
-measurementsofexposureandeffectaremadeatthesametime
-usefulforinvestigatingexposuresthatarefixed
characteristicsofindividuals,suchasethnicity,socio-economicstatusandbloodgroup,orchronic
diseasesorstableconditions
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Typesofepidemiologicalstudy(Observationalstudies)
Cross-sectionalstudies(Prevalencestudies)
-Insuddenoutbreaksofdiseaseitisthemost
convenientfirststepinaninvestigationintothecause
-Raredisease,conditionsofshortdurationor
diseaseswithhighcasefatalityareoftennotdetected
T f id i l i l d
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Typesofepidemiologicalstudy(Observationalstudies)
Cross-sectionalstudies(Prevalencestudies)
-short-termandthereforelesscostly
-providenodirectestimateofrisk
-pronetobiasfromselectivesurvival
-estimatesofprevalencemaybebiasedbytheexclusionofcasesinwhichdeathorrecoveryarerapid
T f id i l i l d
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Typesofepidemiologicalstudy(Observationalstudies)
T f id i l i l d
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Typesofepidemiologicalstudy(Observationalstudies)
Case-controlstudies
-longitudinalstudies(lookingbackwardfromthe
diseasetoapossiblecause)
-usenew(incident)cases
-usedtoinvestigatecause(etiology)ofdisease,esp.
rarediseases
-usedoddsratio
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TablearrangementandformulaforOddsratio(OR)
DiseaseNodiseaseTotal
RiskfactorpresentABA+B
RiskfactorabsentCDC+D
TotalA+CB+D
[A/(A+C)]/[C/(A+C)]A/CADOR=-------------------------------=-------=-------
[B/(B+D)]/[D/(B+D)]B/DBC
T f id i l i l t d
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Typesofepidemiologicalstudy(Observational studies)
Oddsratiomeasureofthestrengthassociation
InterpretationofOddsratio
TheoddsofhavingthediseaseinquestionareOR
timesgreateramongthoseexposedthanthosewithno
exposure
ThelargerthevalueofOR,thestrongertheassociation
betweenthediseaseinquestionandexposuretothe
riskfactor
WhenthevalueofORiscloseto1,thediseaseandthe
exposuretotheriskfactorareunrelated
T f id i l i l t d
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Typesofepidemiologicalstudy(Observationalstudy)
InterpretationofOddsratio
ValueofORlessthan1indicatesanegative
association(i.e.,protectiveeffect)betweentherisk
factorandthedisease
Forraredisease(e.g.,mostchronicdiseaseswith
diseaseprevalenceoflessthan10%),ORapproximatesRR
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Exampleofcase-controlstudy
Associationbetweenrecentmeatconsumptionand
enteritisnecroticansinPapuaNewGuinea
Exposure(recentmeatingestion)
YesNoTotal
DiseaseYes501161
(enteritisnecroticans)No164157
Total6652118
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Exampleofcase-controlstudy
[A/(A+C)]/[C/(A+C)]A/CAD
OR=--------------------------------=--------=-----
[B/(B+D)]/[D/(B+D)]B/DBD
50X41
OR=-------------=11.6
11X16
Thecaseswere11.6timesmorelikelythanthecontrolstohaverecentlyingestedmeat
T pes of epidemiological st d
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Typesofepidemiologicalstudy(Observationalstudies)
Cohort studies
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PastPresentFuture
CohortFollow-up
assembled
Historical
cohort
CohortFollow-upassembled
Concurrent
cohort
Types of epidemiological study
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Typesofepidemiologicalstudy(Observationalstudies)
Cohortstudies
-longitudinalstudies(forward)
-providethebestinformationaboutthecausationofdisease
-mostdirectmeasurementoftheriskofdevelopingdisease
-providethepossibilityofestimatingtheattributablerisks
-userelativerisk
Types of epidemiological study
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Typesofepidemiologicalstudy(Observationalstudies)
Cohortstudies
-mostcloselyresembleexperimentalstudies
-Long-term,notalwaysfeasible-Samplesizerequiredforthestudyextremely
large
-Attritionismostseriousproblem
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Tablearrangementandformulaforrelativerisk(RR)
Disease No Disease Total
Risk factor present A B A + B
Risk factor absent C D C + D
Total A + C B + D
A/(A+B)RR=-----------------
C/(C+D)
Types of epidemiological study
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Typesofepidemiologicalstudy(Observationalstudies)
Interpretationofrelativerisk(RR)
Thedisease(orotherhealthrelatedoutcome)isRR
timesmorelikelytooccuramongthoseexposedthanamongthosewithnoexposure
ThelargerthevalueofRR,thestrongertheassociation
betweenthediseaseinquestionandexposuretothe
riskfactor
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Exampleofcohortstudy
Problem:
Acountyschoolsystemprovideslunchto10,000
schoolchildren.Duringthefirstweekofschool,2,500ofthesechildrenatechickensaladlatershowntobe
contaminatedwithsalmonella.Theentirepopulation
of10,000studentswassubsequentlyfollowedforone
monthtodeterminewhetherexposuretosalmonella
increasedtheriskofdiarrhea.
Example of cohort study
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Exampleofcohortstudy
DiarrheaNoDiarrhea
Exposure(D+)(D-)Totals
E+302,4702,500
E-607,4407,500
Totals909,91010,000
A/(A+B)30/2,500RR=---------------=-----------------=1.5
C/(C+D)60/7,500
1.5timesgreaterthaninchildrenwithnosuchexposure
Advantagesanddisadvantagesofdifferentobservational
study designs
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studydesigns
Probabilityof:
selectionbiasNAmediumhighlow
recallbiasNAhighhighlow
losstofollow-upNANAlowhigh
confoundinghighmediummediumlow
Timerequiredlowmediummediumhigh
Costlowmediummediumhigh
EcologicalCross-Case-Cohort
sectionalcontrol
Applicationsofdifferentobservationalstudydesigns
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Investigationofraredisease++++-+++++-
Investigationofrarecause++--+++++
Testingmultipleeffectof+++-+++++
cause
Studyofmultipleexposure+++++++++++
anddeterminants
Measurementsoftime++-++++++
relationship
Directmeasurementof--++++++
incidence
Investigationoflong--+++-
latentperiods
EcologicalCross-Case-Cohort
sectionalcontrol
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Types of epidemiological study
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Typesofepidemiologicalstudy(Experimentalstudies)
Randomizedcontrolledtrials(RCTs)
- Goldstandardorreferenceinmedicine
- Providethegreatestjustificationfor
concludingcausality
- Subjecttotheleastnumberofproblemsor
biases
- Beststudydesigntoestablishtheefficacyofatreatmentoraprocedure
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BiasinClinicalObservation
Selectionbiasoccurswhencomparisonsare
madebetweengroupsofpatientsthatdifferin
determinantsofoutcomeotherthantheoneunder
study
Measurementbiasoccurswhenthemethodsof
measurementaredissimilaramonggroupsof
patients
Confoundingbiasoccurswhentwofactorsare
associated(traveltogether)andtheeffectofone
isconfusedwithordistortedbytheeffectofthe
other
MethodsofControllingSelectionBias
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PhaseofStudy
MethodDescriptionDesignAnalysis
Randomization Assignpatientstogroupsinawaythat+
giveseachpatientequalchanceof
fallingintooneortheothergroup
Restriction Limittherangeofcharacteristicsof+ofpatientsinthestudy
Matching Foreachpatientinonegroupselectone+
ormorepatientswiththesame
characteristics(exceptfortheone
understudy)foracomparisongroup
StratificationComparerateswithinsubgroups(strata)+
withotherwisesimilarprobabilityofthe
outcome
MethodsforControllingSelectionBias
Ph f St d
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PhaseofStudy
MethodDescriptionDesignAnalysis
Adjustment
SimpleMathematicallyadjustcruderatesforone+
orfewcharacteristicssothatequalweight
isgiventostrataofsimilarrisk
MultipleAdjustfordifferenceinlargenumberoffactors+
relatedtooutcome,usingmathematical
modellingtechniques
Bestcase/Describehowdifferenttheresultscouldbe+
Worsecaseunderthemostextremeorsimplyveryunlikely)
conditionsofselectionbias
Cause
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Clinicalquestion:Whatconditionsleadtodisease?
Whatarethepathogeneticmechanismsofdisease?
Webstersdefinition
somethingthatbringsaboutaneffectora
result
Medicine:etiologypathogenesis
mechanismsorriskfactors
Importance:prevention,diagnosisand
treatmentofdisease
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Cause
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Clinicalquestion:Whatconditionsleadtodisease?
Whatarethepathogeneticmechanismsofdisease?
Multiplecausation(Webofcausation)
Effectsneverdependonsingleisolatedcauses,but
ratherdevelopastheresultofchainsofcausation
inwhicheachlinkitselfistheresultofacomplex
genealogyofantecedents.
Manyfactorsacttogethertocausedisease
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Causesoftuberculosis
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SUSCEPTIBLEHOSTINFECTIONTUBERCULOSIS
Exposureto
Mycobacterium
TissueInvasionandReaction
Crowding
Malnutrition
Vaccination
Genetic
RiskFactorsforMechanismsof
TuberculosisPathogenesisTuberculosis
DistantfromOutcomeProximaltoOutcome
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Relationshipbetweencigarettesmokingandincidencerateof
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p g g
strokeinacohortof118,539women
Neversmoked70395,59417.7
Ex-smoker65232,71227.9
Smoker139280,14149.6
Total274908,44730.2
Smoking Person-y ears Stroke incidence ratecategory No. of cases of observation (per 100,000
of stroke (over 8 years) person-years)
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Comparingdiseaseoccurrenceamong
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exposedandunexposed
Attributablefraction(exposed)
istheproportionofthediseaseinthespecificpopulationthatwouldbeeliminatedintheabsenceofexposure
determinedbydividingtheriskdifferencebytherateofoccurrenceamongtheexposedpopulation
Example:
[(49.617.7)/49.6]x100=64%
Interpretation:Onewouldexpecttoachievea64%reductionintheriskofstrokeamongthewomensmokersifsmokingwerestopped,ontheassumptionthatsmokingisbothcausalandpreventable
Comparingdiseaseoccurrenceamong
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exposedandunexposed
Populationattributablerisk[attributablefraction(population)]
isameasureoftheexcessrateofdiseaseinatotalstudypopulationwhich
isattributabletoanexposure
usefulfordeterminingtherelativeimportanceofexposuresfortheentire
populationandistheproportionbywhichtheincidencerateofthe
outcomeintheentirepopulationwouldbereducedifexposurewere
eliminated.
p
up
pI
IIAF
30.2 17.7= ------------------ = 0.414 o r 41.4%
30.2
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CauseasariskfactorClinical question: What conditions lead to disease ?
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Clinical question: What conditions lead to disease ?What are the pathogenetic mechanisms of disease ?
Usesofriskfactor
1. predicttheoccurrenceofdisease
2. markerofdiseaseoutcome
3. improvethepositivepredictivevalueofa
diagnostictest
4. preventdisease
CauseClinical question: What conditions lead to disease ?
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Clinicalquestion:Whatconditionsleadtodisease?
Whatarethepathogeneticmechanismsofdisease?
Establishingcause
Inclinicalmedicine,itisnotpossibleto
provecausalrelationshipbeyondanydoubt.Itisonlypossibletoincreaseones
convictionofacauseandeffectrelationship,
bymeansofempiricevidence,causeisestablished.
CauseClinical question: What conditions lead to disease ?
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Clinicalquestion:Whatconditionsleadtodisease?
Whatarethepathogeneticmechanismsofdisease?
Establishingcause
Factorsthatareconsideredcausesatonetimearesometimesfoundtobeindirectly
relatedtodiseaselater,whenmore
evidencesareavailable
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Temporal Doesthecauseprecedetheeffect?(essential)
Plausibility Istheassociationconsistentwithotherknowledge?
(mechanismofaction;evidencefromexperimentalanimals)
Consistency Havesimilarresultsbeenshowninotherstudies?
Strength Whatisthestrengthoftheassociationbetweenthecauseand
theeffect?(relativerisk)Dose-response Isincreasedexposuretothepossiblecauseassociated
relationship withincreasedeffect?
Reversibility Doestheremovalofapossiblecauseleadtoreductionof
diseaserisk?Studydesign Istheevidencebasedonastrongstudydesign?
JudgingtheevidenceHowmanylinesofevidenceleadtotheconclusion?
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Naturalhistoryofadiseaseandprognosis
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Clinicalquestion:Whataretheconsequencesofhavingadisease?
Prognosis
isapredictionofthefuturecourseofdiseasefollowingitsonset
Naturalhistoryofdisease
referstothestagesofadisease
a.Natural
b.Clinicalcourse
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Natural history of disease and prognosis
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Clinical question: What are the consequences of having a disease ?
Prognosticfactors
areconditionsthatareassociatedwithagivenoutcomeofthedisease
RiskfactorsPrognosticfactors
eventsbeingcountedisavarietyofconsequences
theonsetofdiseaseofdiseasearecounted
predictlowprobabilitydescriberelativelyfrequent
eventsevents
Natural history of disease and prognosis
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Clinicalquestion:Whataretheconsequenceofhavingadisease?
Multipleprognosticfactorsandpredictionrules
Acombinationoffactorsmaygiveamoreprecise
prognosisthaneachofthesamefactorstakenoneatatime
Clinicalpredictionrulesestimatetheprobabilityof
outcomesaccordingtoasetofpatientcharacteristics
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OutcomesofDisease(theFiveDs)
Death Abadoutcomeifuntimely
Disease Asetofsymptoms,physicalsigns,andlaboratory
abnormalities
Discomfort Symptomssuchaspain,nausea,dyspnea,itching,
andtinnitis
Disability Impairedabilitytogoaboutusualactivitiesathoe,
work,orrecreation
Dissatisfaction Emotionalreactiontodiseaseanditscare,suchas
sadnessoranger
Natural history of disease and prognosis
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Clinical question: What are the consequences of having a disease ?
Descriptionsofprognosisshouldincludethefullrangeofmanifestationsthatwouldbeconsideredimportanttopatients
Cohortsinprognosticstudiesareobservedstartingfromapointintime,,calledzerotime.
Thispointshouldbespecifiedclearlyandbethe
samewell-definedlocationalongthecourseofdisease(e.g.onsetofsymptoms,timeofdiagnosisorbeginningoftreatment)foreachpatient
NaturalhistoryofdiseaseandprognosisClinicalquestion:Whataretheconsequenceofhavingadisease?
Rates Commonl Used to Describe Prognosis
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RatesCommonlyUsedtoDescribePrognosis
RateDefinition
5-yearsurvival Percentofpatientssurviving5yearsfrom
somepointinthecourseoftheirdisease
Casefatality Percentofpatientswithadiseasewhodie
ofit
Disease-specificmortalityNumberofpeopleper10,000population
dyingofaspecificdisease
Response Percentofpatientsshowingsome
evidenceofimprovementfollowingan
interventionRemission Percentofpatientsenteringaphasein
whichdiseaseisnolongerdetectable
Recurrence Percentofpatientswhohavereturnof
diseaseafteradisease-freeinterval
NaturalhistoryofdiseaseandprognosisCli i l i Wh h f h i di ?
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Clinicalquestion:Whataretheconsequencesofhavingadisease?
Survivalanalysis(Kaplan-Meiranalysis)
awayofestimatingthesurvivalofacohortovertime
Lifetableanalysis
TreatmentClinical question: How does treatment change the
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Clinicalquestion:Howdoestreatmentchangethe
courseofdisease?
Usuallytheeffectsoftreatmentaremuchlessobviousandmostinterventionsrequireresearchtoestablishtheirvalue
Specificinterventionsmustdomoregoodthanharmamongpatientswhousethem(efficaciousandeffective)
Themostdesirablemethodformeasuringefficacyandeffectivenessisthatoftherandomizedcontrolledtrial
TreatmentClinicalquestion:Howdoestreatmentchangethe
f di ?
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courseofdisease?
Interventionstudies
Clinicaltrials
Controlledtrials
Uncontrolledtrials
Concurrentcontrol
TreatmentClinicalquestion:Howdoestreatmentchangethe
f di ?
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courseofdisease?
Typesofclinicaltrial(accordingtopurpose)
Prophylactictrials,e.g.immunization,contraception
Therapeutictrials(drugtreatment,surgicalprocedures
Safetytrials(side-effectsofdrug)
Effectivenesstrials(theoretical,use,andextendeduse
effectivenessofcontraceptivemethods)
Riskfactortrials(provingetiologyofdisease)
Efficiencytrials
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TreatmentClinicalquestion:Howdoestreatmentchangethe
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q g
courseofdisease?
Phase3ClinicalTrials(Classicalphase)
performedonpatientswithconsent
carriedoutmostlyonhospitalin-patients
assesstheeffectiveness,safetyandcontinueduse
ofthedrug/device
Phase4ClinicalTrials
atrialinnormalfieldorprogramsettingreassesseffectiveness,safety,acceptabilityand
continueduseofthedrugs
PreventionClinicalquestion:Doesaninterventiononwellpeoplekeep
disease from arising? Does early detection and treatment
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diseasefromarising?Doesearlydetectionandtreatment
improvethecourseofdisease?
Prevention(Webstersdefinition)theactof
keepingfromhappening
Inclinicalmedicine,thedefinitionisrestricted;
dependingonwheninthecourseofdisease
interventionsaremade
PreventionClinicalquestion:Doesaninterventiononwellpeoplekeep
disease from arising? Does early detection and treatment
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diseasefromarising?Doesearlydetectionandtreatment
improvethecourseofdisease?
ASYMPTOMATIC
NODISEASEDISEASECLINICALCOURSE
Onset
Clinical
Diagnosis
PrimarySecondaryTertiary
RemoveriskEarlydetectionReducefactorsandtreatmentcomplications
Levelsofprevention
PreventionClinicalquestion:Doesaninterventiononwellpeoplekeepthe
disease from arising? Does early detection and treatment
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diseasefromarising?Doesearlydetectionandtreatment
improvethecourseofdisease?
LevelofpreventionPhaseofdiseaseTarget
Primary SpecificcausalfactorTotalpopulation,
selectedgroupsandhealthy
individuals
SecondaryEarlystageofdiseasePatients
TertiaryLatestageofdiseasePatients
(treatment,rehabilitation)
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PreventionClinicalquestion:Doesaninterventiononwellpeoplekeep
disease from arising? Does early detection and treatment
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diseasefromarising?Doesearlydetectionandtreatment
improvethecourseofdisease?
Secondaryprevention
Papsmear
Screeningtest
identificationofanunrecognizeddiseaseor
riskfactorbyhistorytaking,physical
examination,laboratorytestorotherprocedurethatcanbeappliedrapidly
Criteriaforinstitutingascreeningprogram
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Disease Serious
Highprevalenceofpreclinicalstage
Naturalhistoryunderstood
Longperiodbetweenfirstsignsandovertdisease
DiagnostictestSensitiveandspecific
Simpleandcheap
Safeandacceptable
Reliable
Diagnosisand Facilitiesareadequate
TreatmentEffective,acceptable,andsafetreatmentavailable
PreventionClinicalquestion:Doesaninterventiononwellpeoplekeep
disease from arising? Does early detection and treatment
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diseasefromarising?Doesearlydetectionandtreatment
improvethecourseofdisease?
Tertiaryprevention
Limitationofdisability
Rehabilitation
Thegoalhereisnottopreventdeathbutto
maximizetheamountofhigh-qualitytimea
patienthasleft.
PreventionClinicalquestion:Doesaninterventiononwellpeoplekeep
disease from arising? Does early detection and treatment
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diseasefromarising?Doesearlydetectionandtreatment
improvethecourseofdisease?
HealthmaintenanceorPeriodichealthexamination
Proceduresareperformedonpatientswithout
specificcomplaints,toidentifyandmodifyriskfactorstoavoidtheonsetortofinddiseaseearly
initscoursesothatbyinterveningpatientsremain
well
CriteriaforDecidingWhetheraMedicalCondition
ShouldBeIncludedinPeriodicHealthExamination
H t i th b d f ff i d b th diti
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1. Howgreatistheburdenofsufferingcausedbytheconditionintermsof:
DeathDiscomfortDiseaseDissatisfaction
DisabilityDestitution
2. Howgoodisthescreeningtest,ifoneistobeperformed,intermsof:
SensitivityCostSpecificitySafety
SimplicityAcceptability
3.a.Forprimaryprevention,howeffectiveistheintervention?
or
b.Forsecondaryprevention,iftheconditionisfound,how
effectiveistheensuingtreatmentintermsof:Efficacy
Patientcompliance
Earlytreatmentbeingmoreeffectivethanlatertreatment
PreventionClinicalquestion:Doesaninterventiononwellpeoplekeepthe
disease from arising? Does early detection and treatment
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diseasefromarising?Doesearlydetectionandtreatment
improvethecourseofdisease?
HealthmaintenanceorPeriodichealthexamination
Howmuchharmforhowmuchgood?
Beforeundertakingahealthpromotionprocedureonapatient,especiallyiftheprocedureis
controversialamongexpertgroups,theclinician
shoulddiscussboththepros(probabilityofand
hopedforhealthbenefits)andcons(probabilityof
unintendedeffects)oftheprocedurewiththe
patient.
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ThankYou
Thespectrumofillnessfromcommunicabledisease
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INAPPARENT MILD SEVERE DEATH
INFECTION DISEASE DISEASE
No signs or Clinical illness with signs and symptoms
symptoms
Origin
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Over2,000yearsago,Hippocratesenvironmentalfactorscaninfluencetheoccurrenceofdisease
Intheearly19thcentury,thedistributionofdiseaseinspecific
humanpopulationgroupswasmeasured
JohnSnowsepidemiologicalstudieson
the risk factor of Cholera in London
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theriskfactorofCholerainLondon
Deaths from Cholera in districts of LondonSupplied by two water companies,8 July to 26 August 1854
WaterSupplyPopulationNo.ofdeathsCholeradeath
Company 1851 fromcholerarateper1000
population
________________________________________________________
Southwark 167,654 844 5.0
Lambeth 19,133 18 0.9
ACHIEVEMENTSINEPIDEMIOLOGY
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EradicationofSmallpox
IdentificationofmethylmercuryMinamata
Disease
IdentificationoffactorscausingRheumaticfever
andRheumaticheartdisease
Iodinedeficiencydisease
AIDS,SARS
PROGNOSIS
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Survivalcurve
1. Actuarialorlifetableanalysis
(Cutler-Ederermethod)
1. Kaplan-Meiercurve
PatientDateofTransplantDatelosttoFollow-upDateofKidneyFailureMonthsinStudy
1111-197948-197822118-197823
3129197823
44419784 241978
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6510197819
751419788 2819783
8521197811 219785966197811 15197817
10 617197818
11 621197818
12 722197811 719783
13 927197815
14 10519781 2019793
15 1022197814
16 111519781317 126197812
18 1212197812
19 21197910
20 216197910
21 4819798
22 41119798
23 41819798
24 62619798 41979125 7319795
26 71219795
27 71819798 119794
28 82319794
29 101619792
30 12121979
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MonthssinceAliveatbeginningRejectionduringWithdrawnaliveor
Entryintostudyofintervalintervallosttofollow-up
nidiWi
0upto23132
2upto42632
4upto621136upto91703
9upto121402
12upto151204
15upto18811
18upto21604
21upto24202
B.ActuarialCalculation
MonthssinceProbabilityofProbabilityofCumulativeProbability
entryintostudyrejectionordeathkidneyretentionofkidneyretention
q d / [n ( /2)] p 1 q s pp p p
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qi=di/[ni(w/2)]pi=1qisi=pipi-1pi-2.p1
0upto23/[31(2/2)]=.10.90.90
2upto43/[26(2/2)]=.12.88.79
4upto61/[21(3/2)]=.05.95.75
6upto90/[17(3/2)]=01.00.75
9upto120/[14(2/2)]=01.00.75
12upto150/[12(4/2)]=01.00.75
15upto181/[8(1/2)]=.13.87.65
18upto210/[6(4/2)]=01.00.65
21upto240/[2(2/2)]=01.00.65
Calculationforconfidencebandforactuarialcurve
iii
ii
wdn
qs
21
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Intervalqinidi wisi
020.1031320.0037
240.1226320.0055
460.0521130.0027
69017030
912014020
121501204015180.138110.0200
182106040
212402020
iii 2