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Using fractional polynomials to model the effect of cumulative duration of exposure on outcomes: applications to cohort and nested case-control designs.

Austin PC, Park-Wyllie LY, Juurlink DN - Pharmacoepidemiol Drug Saf (2014)

Bottom Line: Using a cohort design and a Cox proportional hazards model, we found a non-linear relationship between cumulative duration of use of the antiarrhythmic drug amiodarone and the risk of thyroid dysfunction.Using a nested case-control design and a conditional logistic regression model, we found evidence of a linear relationship between duration of use of bisphosphonate medication and risk of atypical femur fractures.Fractional polynomials allow one to model the relationship between cumulative duration of medication use and adverse outcomes.

View Article: PubMed Central - PubMed

Affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Institute of Health Management, Policy and Evaluation, University of Toronto, Toronto, Ontario, Canada; Schulich Heart Research Program, Sunnybrook Research Institute, Toronto, Canada.

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Relationship between cumulative duration of past amiodarone use and thyroid dysfunction
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fig03: Relationship between cumulative duration of past amiodarone use and thyroid dysfunction

Mentions: The relationship between cumulative duration of daily use of amiodarone and the log-hazard ratio of thyroid dysfunction (relative to a subject with 1 day of amiodarone use) is described in the left panel of Figure 3. The vertical axis denotes the log-hazard ratio comparing the hazard for thyroid dysfunction for a subject with a given cumulative duration of use with that of a subject whose cumulative duration of use was equal to one (i.e. with that of a subject who had used amiodarone for one single day). On the horizontal axis is a rug plot describing the distribution of cumulative duration of amiodarone use at the end of follow-up. We describe the relationship between cumulative duration of amiodarone use and the risk of the outcome as described by the best-fitting FP1 and FP2 transformations and by the identity transformation (i.e. assuming a linear relationship). The FP2 (1, 1) transformation shows the risk of thyroid dysfunction increasing rapidly with increasing cumulative duration of amiodarone use. However, once cumulative duration of use exceeded approximately 700 days, the rate of increase in the risk of thyroid dysfunction begins to attenuate. The risk of thyroid dysfunction eventually begins to decrease with increasing duration of cumulative duration of amiodarone use. This attenuation and decrease may reflect depletion of susceptibles—those subjects who had higher risk for thyroid dysfunction experience an early failure. Alternatively, it may be because of exposure having occurred entirely in the distant past (i.e. subjects have discontinued treatment), and distant exposure may have little impact on the current risk of thyroid dysfunction.


Using fractional polynomials to model the effect of cumulative duration of exposure on outcomes: applications to cohort and nested case-control designs.

Austin PC, Park-Wyllie LY, Juurlink DN - Pharmacoepidemiol Drug Saf (2014)

Relationship between cumulative duration of past amiodarone use and thyroid dysfunction
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230473&req=5

fig03: Relationship between cumulative duration of past amiodarone use and thyroid dysfunction
Mentions: The relationship between cumulative duration of daily use of amiodarone and the log-hazard ratio of thyroid dysfunction (relative to a subject with 1 day of amiodarone use) is described in the left panel of Figure 3. The vertical axis denotes the log-hazard ratio comparing the hazard for thyroid dysfunction for a subject with a given cumulative duration of use with that of a subject whose cumulative duration of use was equal to one (i.e. with that of a subject who had used amiodarone for one single day). On the horizontal axis is a rug plot describing the distribution of cumulative duration of amiodarone use at the end of follow-up. We describe the relationship between cumulative duration of amiodarone use and the risk of the outcome as described by the best-fitting FP1 and FP2 transformations and by the identity transformation (i.e. assuming a linear relationship). The FP2 (1, 1) transformation shows the risk of thyroid dysfunction increasing rapidly with increasing cumulative duration of amiodarone use. However, once cumulative duration of use exceeded approximately 700 days, the rate of increase in the risk of thyroid dysfunction begins to attenuate. The risk of thyroid dysfunction eventually begins to decrease with increasing duration of cumulative duration of amiodarone use. This attenuation and decrease may reflect depletion of susceptibles—those subjects who had higher risk for thyroid dysfunction experience an early failure. Alternatively, it may be because of exposure having occurred entirely in the distant past (i.e. subjects have discontinued treatment), and distant exposure may have little impact on the current risk of thyroid dysfunction.

Bottom Line: Using a cohort design and a Cox proportional hazards model, we found a non-linear relationship between cumulative duration of use of the antiarrhythmic drug amiodarone and the risk of thyroid dysfunction.Using a nested case-control design and a conditional logistic regression model, we found evidence of a linear relationship between duration of use of bisphosphonate medication and risk of atypical femur fractures.Fractional polynomials allow one to model the relationship between cumulative duration of medication use and adverse outcomes.

View Article: PubMed Central - PubMed

Affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Institute of Health Management, Policy and Evaluation, University of Toronto, Toronto, Ontario, Canada; Schulich Heart Research Program, Sunnybrook Research Institute, Toronto, Canada.

Show MeSH
Related in: MedlinePlus