title: Changes in causes of death over time after treatment for invasive aspergillosis.
abstract: BACKGROUND
  Assessment of response to invasive aspergillosis (IA) therapy has been challenging in treatment trials.
  
  
  METHODS
  The causes of death over 12 weeks were categorized prospectively by a blinded data review committee using a priori defined criteria in participants in a randomized comparative trial of voriconazole versus amphotericin B as first-line therapy of proven or probable IA.
  
  
  RESULTS
  Death occurred in 98 of 277 patients during the 12-week course of study. Seventy-three of the 98 deaths (74%) occurred in the first 6 weeks; 25 deaths occurred during the second 6 weeks. Of the 73 deaths during the first 6 weeks, 50 (68%) were judged to be attributable to IA. Of the 25 deaths during the second 6 weeks, only 6 (24%) were judged to be attributable to IA. Fifty of the 56 deaths (89%) attributable to IA occurred during the first 6 weeks.
  
  
  CONCLUSIONS
  These data suggest that most deaths due to IA occur during the first 6 weeks after the start of therapy and 6 weeks may be a better interval to judge the effectiveness of antifungal therapy because most deaths after 6 weeks are due to causes related to the underlying disease and its treatment rather than due to IA. Attributable mortality when assessed using a priori definitions and conducted in a blinded manner by a central data review committee can be useful in the assessment of IA therapy.
authors.affiliation: Department of Medicine, University of Florida College of Medicine, Gainesville, Florida 32610-3633, USA. wingajr@medicine.ufl.edu
authors.forename: John R
authors.initials: JR
authors.lastname: Wingard
authors.forename: Patricia
authors.initials: P
authors.lastname: Ribaud
authors.forename: Haran T
authors.initials: HT
authors.lastname: Schlamm
authors.forename: Raoul
authors.initials: R
authors.lastname: Herbrecht
mesh_terms: D000666:Amphotericin B / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000401:mortality*; D002423:Cause of Death; D006086:Graft vs Host Disease / Q000150:complications*; D006801:Humans; D009369:Neoplasms / Q000150:complications*; D011743:Pyrimidines / Q000627:therapeutic use*; D015996:Survival Rate; D013997:Time Factors; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D000666:Amphotericin B; D065819:Voriconazole