Tiffany L Breger1, Jessie K Edwards1, Stephen R Cole1, Michael Saag2, Peter F Rebeiro3, Richard D Moore4, Joseph J Eron5. 1. From the Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC. 2. Department of Medicine, University of Alabama Birmingham, Birmingham, AL. 3. Department of Medicine and Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN. 4. Department of Medicine, Johns Hopkins University, Baltimore, MD. 5. Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Abstract
BACKGROUND: There are few methodologic examples of how multiple causes of death may be summarized in cause-specific mortality analyses to address limitations of attributing death to a single underlying cause. We propose a cause-of-death weighting approach to estimate the set of risk functions of specific causes of mortality using both underlying and contributing cause-of-death information. METHODS: We constructed weights according to a user-specified function. Using data from four southern US human immunodeficiency virus (HIV) clinics, we constructed a cause of death-weighted Aalen-Johansen estimator of the cumulative incidence function to estimate risks of five specific causes of mortality in the full sample and by injection drug use history. RESULTS: Among 7740 HIV-positive patients initiating antiretroviral therapy between 1999 and 2014, the 8-year risk of all-cause mortality was 17.5% [95% confidence interval (CI) = 16.5, 18.4]. The cause of death-weighted risk of HIV-related mortality was 6.7% (95% CI = 6.0, 7.3) and accounted for 39% (95% CI = 35, 42) of total mortality risk. This compared with 10.2% (95% CI = 9.2, 11.2) using only the underlying cause, in which case HIV-related deaths accounted for nearly 60% of total mortality risk. The proportion attributable to cardiovascular disease among those whose HIV risk factor was injection drug use was twice as high using cause-of-death weights compared with only the underlying cause (8%; 95% CI = 5, 11 vs 4%; 95% CI = 1, 6). CONCLUSION: Using cause of death-weighted estimators to incorporate multiple causes of death may yield different conclusions regarding the importance of certain causes of mortality. See video abstract: http://links.lww.com/EDE/B706.
BACKGROUND: There are few methodologic examples of how multiple causes of death may be summarized in cause-specific mortality analyses to address limitations of attributing death to a single underlying cause. We propose a cause-of-death weighting approach to estimate the set of risk functions of specific causes of mortality using both underlying and contributing cause-of-death information. METHODS: We constructed weights according to a user-specified function. Using data from four southern US human immunodeficiency virus (HIV) clinics, we constructed a cause of death-weighted Aalen-Johansen estimator of the cumulative incidence function to estimate risks of five specific causes of mortality in the full sample and by injection drug use history. RESULTS: Among 7740 HIV-positive patients initiating antiretroviral therapy between 1999 and 2014, the 8-year risk of all-cause mortality was 17.5% [95% confidence interval (CI) = 16.5, 18.4]. The cause of death-weighted risk of HIV-related mortality was 6.7% (95% CI = 6.0, 7.3) and accounted for 39% (95% CI = 35, 42) of total mortality risk. This compared with 10.2% (95% CI = 9.2, 11.2) using only the underlying cause, in which case HIV-related deaths accounted for nearly 60% of total mortality risk. The proportion attributable to cardiovascular disease among those whose HIV risk factor was injection drug use was twice as high using cause-of-death weights compared with only the underlying cause (8%; 95% CI = 5, 11 vs 4%; 95% CI = 1, 6). CONCLUSION: Using cause of death-weighted estimators to incorporate multiple causes of death may yield different conclusions regarding the importance of certain causes of mortality. See video abstract: http://links.lww.com/EDE/B706.
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