title: Multimorbidity, polypharmacy, referrals, and adverse drug events: are we doing things well?
abstract: BACKGROUND
  The consequences of multimorbidity include polypharmacy and repeated referrals for specialised care, which may increase the risk of adverse drug events (ADEs).
  
  
  OBJECTIVE
  The objective of this study was to analyse the influence of multimorbidity, polypharmacy,  and multiple referrals on the frequency of ADEs, as an indicator of therapeutic safety, in the context of a national healthcare system.
  
  
  METHODS
  This was a multicentre, retrospective, observational study of 79 089 adult patients treated during 2008 in primary  care centres.
  
  
  METHODS
  The explanatory patient variables sex, age, level of multimorbidity, polypharmacy, number of primary care physician visits, and number of different specialties attended were analysed. The response variable was the occurrence of ADEs. Logistic regression  models were used to identify associations among the analysed variables.
  
  
  RESULTS
  The prevalence of individuals with at least one ADE was 0.88%. Multivariate analysis identified the following variables as risk factors for the occurrence of ADE in descending order of effect  size: multimorbidity level (odds ratio [OR]Veryhigh/Low = 45.26; ORHigh/Low = 17.58; ORModerate/Low = 4.25), polypharmacy (OR = 1.34), female sex (OR = 1.31), number of different specialties (OR = 1.20), and number of primary care physician visits (OR = 1.01). Age, however, did not show statistical  significance (OR = 1.00; 95% confidence interval = 0.996 to 1.005).
  
  
  CONCLUSIONS
  The results of this study demonstrate that multimorbidity is strongly related to the occurrence of ADEs, insofar as it requires the intervention of multiple specialties and the prescription of  multiple medications. Further research should shed light on the causal pathway between multimorbidity and increased risk of adverse events.
authors.affiliation: Aragón Health Sciences Institute (IACS), IIS Aragón, Miguel Servet University Hospital, University of Zaragoza, Spain. acalderon.iacs@aragon.es
authors.forename: Amaia
authors.initials: A
authors.lastname: Calderón-Larrañaga
authors.forename: Beatriz
authors.initials: B
authors.lastname: Poblador-Plou
authors.forename: Francisca
authors.initials: F
authors.lastname: González-Rubio
authors.forename: Luis Andrés
authors.initials: LA
authors.lastname: Gimeno-Feliu
authors.forename: José María
authors.initials: JM
authors.lastname: Abad-Díez
authors.forename: Alexandra
authors.initials: A
authors.lastname: Prados-Torres
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019338:Polypharmacy; D012017:Referral and Consultation / Q000706:statistics & numerical data*; D012189:Retrospective Studies; D012307:Risk Factors; D013030:Spain; D055815:Young Adult