title: Measuring trends of outpatient antibiotic use in Europe: jointly modelling longitudinal data in defined daily doses and packages.
abstract: OBJECTIVE
  To complement analyses of the linear trend and seasonal fluctuation of European outpatient antibiotic use expressed in defined daily doses (DDD) by analyses of data in packages, to assess the agreement between both measures and to study changes in the number of DDD per package over time.
  
  
  METHODS
  Data on outpatient antibiotic use, aggregated at the level of the active substance (WHO version 2011) were collected from 2000 to 2007 for 31 countries and expressed in DDD and packages per 1000 inhabitants per day (DID and PID, respectively). Data expressed in DID and PID were analysed separately using non-linear mixed models while the agreement between these measurements was analysed through a joint non-linear mixed model. The change in DDD per package over time was studied with a linear mixed model.
  
  
  RESULTS
  Total outpatient antibiotic and penicillin use in Europe and their seasonal fluctuation significantly increased in DID, but not in PID. The use of combinations of penicillins significantly increased in DID and in PID. Broad-spectrum penicillin use did not increase significantly in DID and decreased significantly in PID. For all but one subgroup, country-specific deviations moved in the same direction whether measured in DID or PID. The correlations are not perfect. The DDD per package increased significantly over time for all but one subgroup.
  
  
  CONCLUSIONS
  Outpatient antibiotic use in Europe shows contrasting trends, depending on whether DID or PID is used as the measure. The increase of the DDD per package corroborates the recommendation to adopt PID to monitor outpatient antibiotic use in Europe.
authors.affiliation: Interuniversity Institute for Biostatistics and Statistical Bioinformatics (I-BIOSTAT), University of Hasselt, Diepenbeek, Belgium robin.bruyndonckx@uhasselt.be.
authors.forename: Robin
authors.initials: R
authors.lastname: Bruyndonckx
authors.affiliation: Interuniversity Institute for Biostatistics and Statistical Bioinformatics (I-BIOSTAT), University of Hasselt, Diepenbeek, Belgium Centre for Health Economic Research and Modelling Infectious Diseases (CHERMID), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.
authors.forename: Niel
authors.initials: N
authors.lastname: Hens
authors.affiliation: Interuniversity Institute for Biostatistics and Statistical Bioinformatics (I-BIOSTAT), University of Hasselt, Diepenbeek, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Aerts
authors.affiliation: Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.
authors.forename: Herman
authors.initials: H
authors.lastname: Goossens
authors.affiliation: Interuniversity Institute for Biostatistics and Statistical Bioinformatics (I-BIOSTAT), University of Hasselt, Diepenbeek, Belgium Interuniversity Institute for Biostatistics and Statistical Bioinformatics (I-BIOSTAT), Catholic University of Leuven, Leuven, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Molenberghs
authors.affiliation: Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium Centre for General Practice, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.
authors.forename: Samuel
authors.initials: S
authors.lastname: Coenen
mesh_terms: D000553:Ambulatory Care / Q000379:methods*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004363:Drug Utilization / Q000639:trends*; D005060:Europe; D008137:Longitudinal Studies; D015233:Models, Statistical
chemical_list: D000900:Anti-Bacterial Agents
keywords: ambulatory care; antibiotic consumption; dose change; non-linear mixed model