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  • 9 semester, Kursus iKlinisk Farmakologi og Forordningslre

    Forelsning:Farmakoepidemiologi Farmakogenetik

    21 Februar 2005

  • Farmakoepidemiology

    Definition: Undersgelse af rsager til og resultater af at anvende lgemidler i befolkningen.

    Udfald er bde

    Positive (forebyggelse, lindring, get livskvalitet, helbredelse, )Negative (bivirkninger, misbrug, sygdom, . )

    Et vigtigt forml med

    farmakoepidemiologien

    er

    Rationel og adkvat anvendelse af lgemidler

    bde ud fra en klinisk og konomisk synsvinkel

    og for den enkelte og for samfundet

  • Statist. Med. 2004; 23:783801

  • Den nye medicinforbruger:

    Receptpligtig medicin vil udgre 1/3 af vksten p det offentlige omrde frem til 2010 (Amternes nye magasin 27/1-03)

    Nye anvendelsesomrder for SSRI:Spiseforstyrrelser, rygestop, social fobi, panikangst

    3 former for risikohndtering:

    Traditionel (Gud, skbne, karma, memesis) Moderne (videnskabeligt baseret, stat. Faktorer Postmoderne (at krve, at vlge)

  • Farmakoepidemiologien anvender de klassiske epidemiologiske metoder:

    Statistikker

    Kohorte studie

    Case

    control studier

    Fortoklning

    af : Relativ Risiko Odds Ratio

    RR = 1,02 ( 0.85

    1.25): 2% get risiko, ikke signifikantRR = 2.21 ( 1.25 -

    3.31)

    2.21 x get risiko, signifikant

    RR = 0.45 ( 0.30

    0.80) 55% reduceret risiko ???

  • Compliance

  • SSRI and pregnancy outcome

    SSRIs are widely used Exposure in 1st trimester of unplanned

    pregnancies Animal studies Cardiovascular congenital malformations

  • Objective

    To examine the risk of adverse pregnancy and neonatal outcomes associated with maternal use of SSRIs during the pregnancy

  • Setting

    4 Counties in Denmark

    ~1.6 million people

    151,962 women who had a live birth or stillbirth identified through the Medical Birth Registry

  • Data on use of SSRIs

    County prescription databases- All redeemed prescriptions- The Anatomical Therapeutic Chemical

    Classification System

  • Data on birth outcomes

    Danish Medical Birth Registry:- birth weight- gestational age- stillbirth- perinatal death

    County Hospital Discharge Registries:- congenital malformations

  • Analysis and data on confounders

    Logistic regression Danish Medical Birth Registry

    - maternal age - maternal smoking - parity

    County prescription databases- maternal use of antiepileptic drugs

  • Methods

    Group

    SSRI exposure during

    Outcome30 days before

    1. trimes.

    2. trimes.

    3. trimes.

    1 Yes Yes Malform.

    2 Yes Yes Yes Still birthPerinatal Low BWPreterm

    Control No No No No

  • Results

    SSRI Control Adj. ORMalformations(overall)

    54 (5.1%) 5,240 (3.5%)

    1.4*(1.1-1.9)

    Malformations(cardiovascular)

    17 (1.7%) 1,000 (1.0%)

    1.6*(1.0-2.6)

    *Adj for maternal smoking status, birthorder, maternal age, and maternal use of antiepileptics

  • ResultsSSRI Control Adj. OR

    Stillbirth 3 (0.3%) 453 (0.3%)

    Perinat. death

    3 (0.3%) 382 (0.3%)

    Low BW 52 (5.2%) 6,392 (4.2%) 1.1(0.7-1.7)

    Preterm 74 (7.4%) 7,580 (5.0%) 1.4(1.1-1.7)

  • Wogelius et al. Epidemiology 2006; 17:701-04

  • Conclusion

    increased risk of

    preterm birth, congenital malformations, congenital cardiovascular malformations

    - associated with prenatal exposure toSSRIs

  • Strengths

    Complete prescription database: prevents selection bias

    Exposure measurements not based on recall High number of exposed pregnancies Confounder control

  • Limitations

    ? Surveillance bias- Newborn SSRI exposed children may be surveyed more intensely due to neonatal symptoms after exposure to SSRI in late pregnancy

    ? Confounding by indication- No information on the depression

  • Nature 405:857, 2000

  • Prediction of drug efficacy by SingleNucleotidePolymorphismss

  • MTHFR 677C>T MTHFR 1298A>C

    Advanced colo-rectal cancer with metastasis and 5-FU treatmenMarie-Christine Etienne et al. Pharmacogenetics 2004, 14:785792

  • The future is here already:

    Individualised risk assessment from genetic analysis

    Individualized drug treatment from genetic analysis

  • Fredag d. 23.2

    Kl 08:15 Holdundervisning

    Kl. 9:15 Repetion Forelsning Lundsgrd Auditorium

    Kl. 10:15 Obs.: FRIVILLIG PRVEEKSAMEN i receptskrivning

    Slide Number 1Slide Number 2Slide Number 3Slide Number 4Slide Number 5Slide Number 6SSRI and pregnancy outcomeObjective SettingData on use of SSRIsData on birth outcomesAnalysis and data on confoundersMethodsResultsResultsSlide Number 16ConclusionStrengthsLimitationsSlide Number 20Slide Number 21Slide Number 22Slide Number 23Slide Number 24Slide Number 25Slide Number 26Slide Number 27Slide Number 28Slide Number 29Slide Number 30Slide Number 31Slide Number 32