Browsing by Subject "Competing Risk"

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    Building Prediction Models for Dementia: The Need to Account for Interval Censoring and the Competing Risk of Death
    (2019-08) Marchetti, Arika L.; Bakoyannis, Giorgos; Li, Xiaochun; Gao, Sujuan; Yiannoutsos, Constantin
    Context. Prediction models for dementia are crucial for informing clinical decision making in older adults. Previous models have used genotype and age to obtain risk scores to determine risk of Alzheimer’s Disease, one of the most common forms of dementia (Desikan et al., 2017). However, previous prediction models do not account for the fact that the time to dementia onset is unknown, lying between the last negative and the first positive dementia diagnosis time (interval censoring). Instead, these models use time to diagnosis, which is greater than or equal to the true dementia onset time. Furthermore, these models do not account for the competing risk of death which is quite frequent among elder adults. Objectives. To develop a prediction model for dementia that accounts for interval censoring and the competing risk of death. To compare the predictions from this model with the predictions from a naïve analysis that ignores interval censoring and the competing risk of death. Methods. We apply the semiparametric sieve maximum likelihood (SML) approach to simultaneously model the cumulative incidence function (CIF) of dementia and death while accounting for interval censoring (Bakoyannis, Yu, & Yiannoutsos, 2017). The SML is implemented using the R package intccr. The CIF curves of dementia are compared for the SML and the naïve approach using a dataset from the Indianapolis Ibadan Dementia Project. Results. The CIF from the SML and the naïve approach illustrated that for healthier individuals at baseline, the naïve approach underestimated the incidence of dementia compared to the SML, as a result of interval censoring. Individuals with a poorer health condition at baseline have a CIF that appears to be overestimated in the naïve approach. This is due to older individuals with poor health conditions having an elevated risk of death. Conclusions. The SML method that accounts for the competing risk of death along with interval censoring should be used for fitting prediction/prognostic models of dementia to inform clinical decision making in older adults. Without controlling for the competing risk of death and interval censoring, the current models can provide invalid predictions of the CIF of dementia.
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    Risk of Lower Extremity Amputation Revision in Patients with Peripheral Vascular Disease Adjusting for a Competing Risk of Death
    (2019-08) Severance, Sarah Elizabeth; Bakoyannis, Giorgos; Yiannoutsos, Constantin; Perkins, Susan; Katz, Barry
    Objectives: The aims of this study are to estimate the cumulative incidence of lower extremity amputation (LEA) revision and reamputation adjusting for a competing risk of death, estimate the one-year event-free mortality rates for patients with peripheral vascular disease undergoing LEA, and develop predictive models for LEA revision and reamputation adjusting for a competing risk of death. Methods: This was a retrospective review of the prospectively collected Vascular Quality Initiative (VQI) registry between 2013 and 2018. Adults undergoing unilateral LEA were included. Demographics, comorbidities, medications, smoking status, history of vascular procedures and revascularization attempts, and procedure urgency were considered. Models to predict LEA revision and reamputation were developed using multivariable regression on the interval-censored competing risks data using semiparametric regression on the cumulative incidence function. Results: The cumulative incidences of LEA revision and revision-free mortality within one year of index amputation are 14.9% and 15.5% respectively. Patient BMI, smoking status, aspirin use, history of revascularization, and level of planned LEA are significantly associated with the odds of LEA revision. Age, amputation urgency, dialysis, and level of planned LEA are associated with the one-year odds of revision-free mortality. A patient receiving an index above knee amputation (AKA) has 61% lower odds of LEA revision (p < 0.0001) but 51% higher odds of revision-free mortality following LEA (p < 0.0001). Previous revascularization procedures increase the odds of revision by 23% (p < 0.0001). The cumulative incidences of reamputation and one-year reamputation-free mortality following LEA are 11.5% and 16.9% respectively. Urgency of the procedure, history of revascularization procedures, and level of planned LEA are statistically associated with the odds of reamputation when adjusting for the competing risk of death. Patients receiving index AKA have 62% lower odds of reamputation (p < 0.0001) compared to BKA. Dialysis is the strongest predictor of one-year mortality (OR 2.576, p < 0.0001). Conclusions: Patients with appropriately managed PVD, which still progresses to amputation have higher odds of LEA revision and reamputation. Revision risk can be predicted and compared on the basis of patient factors and the planned index amputation.
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    Survival Analysis for the Association between Anti-hypertensive Medication and Time to Dementia with Competing Risk
    (2019-06) Hu, Xinhua Flora; Gao, Sujuan; Zhang, Ying; Katz, Barry P.
    Background: High blood pressure (HBP) is a common risk factor for dementia in elder population. Anti-hypertensive medications have been reported to associate with lower incidence rate of dementia in elder African Americans. The Apolipoprotein E (ApoE) epsilon 4 allele has been shown to be associated with both increased dementia and hypertension risk. However, previous studies had not examined the association between anti-hypertensive medications by ApoE status accounting for the competing risk from death. Methods: This is a prospective observational cohort study in 1236 community-dwelling hypertensive African Americans aged 65 years and older without dementia at baseline, with follow-up cognitive assessment and clinical evaluation for dementia diagnosis. Dementia-free mortality was considered as the competing risk. Of these, 707 participants were genotyped for ApoE status. Anti-hypertensive medication use was obtained from prescription records in the electronic medical records of the Indiana Network for Patient Care (INPC). Cox proportional cause-specific hazard (CSH) regression models were applied to assess the association between anti-hypertensive medication use and CSHs for dementia and death in ApoE epsilon 4 carriers and non-carriers separately. Key results: In ApoE epsilon 4 carriers, participants using anti-hypertensive medications had lower CSH of dementia compared to those not on anti-hypertensive medications before adjusting for blood pressure (BP) (hazard ratio (HR), 0.365; 95% CI, 0.170 – 0.785; p = 0.0099). The HR was no longer significant once BP control was adjusted (HR, 0.784; 95% CI, 0.197 – 3.123; p = 0.7303). Anti-hypertensive medications were not associated with dementia rate in non-carriers. In ApoE epsilon 4 non-carriers, participants on anti-hypertensive treatment showed significantly lower CSH of death compared to those not on mediations adjusting for covariates and BP control (HR, 0.237; 95% CI, 0.149 – 0.375; p < 0.0001). There was no significant association between anti-hypertensive medication use and death in ApoE epsilon 4 carriers. Conclusions: Anti-hypertensive medication was associated with lower dementia rate in ApoE epsilon 4 carriers and that rate was primarily mediated through BP control. In non-carriers, anti-hypertensive medication was significantly associated with lower mortality rate and this association appears to be independent of BP control.