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Recurrent event frailty models reduced time-varying and other biases in evaluating transfusion protocols for traumatic hemorrhage

  • Sangbum Choi
    Affiliations
    Division of Clinical and Translational Sciences, Department of Internal Medicine, The University of Texas Health Science Center at Houston, 6410 Fannin Street, UT Professional Building, Suite 1100.05, Houston, TX 77030, USA

    Department of Statistics, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, South Korea
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  • Mohammad H. Rahbar
    Correspondence
    Corresponding author. Tel.: 713-500-7901; fax: 713-500-0766.
    Affiliations
    Division of Clinical and Translational Sciences, Department of Internal Medicine, The University of Texas Health Science Center at Houston, 6410 Fannin Street, UT Professional Building, Suite 1100.05, Houston, TX 77030, USA

    Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Sciences Center at Houston, 1200 Pressler Street, Houston, TX 77030, USA
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  • Jing Ning
    Affiliations
    Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1400 Pressler St, Unit Number: 1411, Houston, TX 77030, USA
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  • Deborah J. del Junco
    Affiliations
    Center for Translational Injury Research, Division of Acute Care Surgery, Department of Surgery, The University of Texas Health Science Center at Houston, 6410 Fannin Street, UT Professional Building, Houston, TX 77030, USA
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  • Elaheh Rahbar
    Affiliations
    Department of Biomedical Engineering, Wake Forest University Health Sciences, 575 N. Patterson Ave., Suite 120, Winston-Salem, NC 27101, USA
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  • Chuan Hong
    Affiliations
    Department of Biostatistics, School of Public Health, The University of Texas Health Sciences Center at Houston, 1200 Pressler Street, Houston, TX 77030, USA
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  • Jin Piao
    Affiliations
    Department of Biostatistics, School of Public Health, The University of Texas Health Sciences Center at Houston, 1200 Pressler Street, Houston, TX 77030, USA
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  • Erin E. Fox
    Affiliations
    Center for Translational Injury Research, Division of Acute Care Surgery, Department of Surgery, The University of Texas Health Science Center at Houston, 6410 Fannin Street, UT Professional Building, Houston, TX 77030, USA
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  • John B. Holcomb
    Affiliations
    Center for Translational Injury Research, Division of Acute Care Surgery, Department of Surgery, The University of Texas Health Science Center at Houston, 6410 Fannin Street, UT Professional Building, Houston, TX 77030, USA
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      Abstract

      Objective

      Transfusion research seeks to improve survival for severely injured and hemorrhaging patients using optimal plasma and platelet ratios over red blood cells (RBCs). However, most published studies comparing different ratios are plagued with serious bias and ignore time-varying effects. We applied joint recurrent event frailty models to increase validity and clinical utility.

      Study Design and Setting

      Using the PRospective Observational Multicenter Major Trauma Transfusion study data, our joint random-effects models estimated the association of (1) clinical covariates with transfusion rate intensities and (2) varying plasma:RBC and platelet:RBC ratios with survival over the 24 hours after hospital admission. Along with survival time, baseline patient vital signs, laboratory values, and longitudinal data on types and volumes of transfusions were included.

      Results

      Baseline systolic blood pressure, heart rate, pH, and hemoglobin were significantly associated with RBC transfusion rates. Increased transfusion rates (per hour) of plasma (P = 0.05), platelets (P < 0.001), or RBCs were associated with increased 24-hour mortality. Higher ratios of plasma:RBC (P = 0.107) and platelet:RBC (P < 0.001) were associated with reduced mortality in a time-varying pattern (P < 0.001).

      Conclusions

      The proposed joint analysis of transfusion rates and ratios offers a more valid statistical approach to evaluate survival effects in the presence of informative censoring by early death.

      Keywords

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