title: Recurrent event frailty models reduced time-varying and other biases in evaluating transfusion protocols for traumatic hemorrhage.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Sangbum
authors.initials: S
authors.lastname: Choi
authors.affiliation: 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. Electronic address: mohammad.h.rahbar@uth.tmc.edu.
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Rahbar
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1400 Pressler St, Unit Number: 1411, Houston, TX 77030, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Ning
authors.affiliation: 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.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Del Junco
authors.affiliation: Department of Biomedical Engineering, Wake Forest University Health Sciences, 575 N. Patterson Ave., Suite 120, Winston-Salem, NC 27101, USA.
authors.forename: Elaheh
authors.initials: E
authors.lastname: Rahbar
authors.affiliation: Department of Biostatistics, School of Public Health, The University of Texas Health Sciences Center at Houston, 1200 Pressler Street, Houston, TX 77030, USA.
authors.forename: Chuan
authors.initials: C
authors.lastname: Hong
authors.affiliation: Department of Biostatistics, School of Public Health, The University of Texas Health Sciences Center at Houston, 1200 Pressler Street, Houston, TX 77030, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Piao
authors.affiliation: 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.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Fox
authors.affiliation: 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.
authors.forename: John B
authors.initials: JB
authors.lastname: Holcomb
mesh_terms: D015982:Bias; D001803:Blood Transfusion; D006470:Hemorrhage / Q000209:etiology* / Q000628:therapy*; D006801:Humans; D015233:Models, Statistical; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D015203:Reproducibility of Results; D013995:Time; D014947:Wounds and Injuries / Q000150:complications*
keywords: Hemorrhage; Joint modeling; Multivariate recurrent events; Survival analysis; Transfusion ratio; Trauma