title: Global differences in causes, management, and survival after severe trauma: the recombinant activated factor VII phase 3 trauma trial.
abstract: BACKGROUND
  Little is known about international variation in mortality after severe trauma. This study examines variation in mortality, injury severity, and case management among countries from a recent prospective multinational trauma trial.
  
  
  METHODS
  This trauma trial was a prospective, randomized, double-blinded, multicenter comparison of recombinant activated factor VII versus placebo in severely injured bleeding trauma patients. Differences in baseline patient characteristics, case management, and clinical outcomes were examined for the 11 countries recruiting most patients. Between-country differences in mortality were examined using regression analysis adjusting for case mix and case management differences. Global predictors of mortality were also identified using multivariate regression analysis.
  
  
  RESULTS
  Significant differences were observed between countries in unadjusted mortality rates at 24 hours (p = 0.025) and 90 days (p < 0.0001). When adjusting for differences in case mix and case management, the between country differences in mortality at 24 hours and 90 days remained significant. Consistent independent predictors of 24-hour, 24-hour to 90-day, and 90-day mortality were admission lactate >or=5 mmol/L (odds ratio: 9.06, 3.56, and 5.39, respectively) and adherence to clinical management guidelines (odds ratio: 4.92, 5.90, and 3.26, respectively). On average, the damage control surgery guideline was less well adhered to than the RBC transfusion and ventilator guidelines. There was statistically significant variation between countries with respect to adherence to the RBC transfusion guideline.
  
  
  CONCLUSIONS
  Considering international variation in mortality when designing or interpreting results from multinational trauma studies is important. Significant differences in mortality persisted between patients from different countries after case mix and case management adjustment. Adherence to clinical guidelines was associated with improved survival. Stratification, case mix adjustment, and use of guidelines on damage control surgery, transfusion, and ventilation may mitigate country-driven variation in mortality.
authors.affiliation: Regulatory Affairs, Novo Nordisk A/S, Søborg, Denmark. mcrc@novonordisk.com
authors.forename: Michael C
authors.initials: MC
authors.lastname: Christensen
authors.forename: Michael
authors.initials: M
authors.lastname: Parr
authors.forename: Bartholomew J
authors.initials: BJ
authors.lastname: Tortella
authors.forename: Johan
authors.initials: J
authors.lastname: Malmgren
authors.forename: Stephen
authors.initials: S
authors.lastname: Morris
authors.forename: Todd
authors.initials: T
authors.lastname: Rice
authors.forename: John B
authors.initials: JB
authors.lastname: Holcomb
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D015984:Causality; D002423:Cause of Death; D015897:Comorbidity; D004311:Double-Blind Method; D017707:Erythrocyte Transfusion / Q000379:methods; D015942:Factor VIIa / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D017052:Hospital Mortality / Q000639:trends*; D006801:Humans; D015601:Injury Severity Score; D007391:International Cooperation; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D012016:Reference Values; D012044:Regression Analysis; D018570:Risk Assessment; D012737:Sex Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D014947:Wounds and Injuries / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy; D055815:Young Adult
chemical_list: D015942:Factor VIIa