title: Current guidelines poorly address multimorbidity: pilot of the interaction matrix method.
abstract: OBJECTIVE
  To develop a framework to identify and classify interactions within and among treatments and conditions and to test this framework with guidelines on chronic heart failure (CHF) and its frequent comorbidity.
  
  
  METHODS
  Text analysis of evidence-based clinical practice guidelines on CHF and 18 conditions co-occurring in ≥5% of CHF patients (2-4 guidelines per disease). We extracted data on interactions between CHF and comorbidity and key recommendations on diagnostic and therapeutic management. From a subset of data, we derived 13 subcategories within disease-disease (Di-Di-I), disease-drug (Di-D-I), drug-drug interactions (DDI) and synergistic treatments. We classified the interactions and tested the interrater reliability, refined the framework, and agreed on the matrix of interactions.
  
  
  RESULTS
  We included 48 guidelines; two-thirds provided information about comorbidity. In total, we identified N = 247 interactions (on average, 14 per comorbidity): 68 were Di-Di-I, 115 were Di-D-I, 12 were DDI, and 52 were synergisms. All 18 comorbidities contributed at least one interaction.
  
  
  CONCLUSIONS
  The interaction matrix provides a structure to present different types of interactions between an index disease and comorbidity. Guideline developers may consider the matrix to support clinical decision making in multimorbidity. Further research is needed to show its relevance to improve guidelines and health outcomes.
authors.affiliation: Institute of General Practice, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany. Electronic address: muth@allgemeinmedizin.uni-frankfurt.de.
authors.forename: Christiane
authors.initials: C
authors.lastname: Muth
authors.affiliation: Institute of General Practice, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany; Department of Primary Medical Care, University Medical Centre Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Kirchner
authors.affiliation: Department of Family Medicine, School CAPHRI, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands; Department of General Practice, Katholieke Universiteit Leuven, Kapucijnenvoer 33, blok J, 3000 Leuven, Belgium.
authors.forename: Marjan
authors.initials: M
authors.lastname: van den Akker
authors.affiliation: Department of Primary Medical Care, University Medical Centre Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Scherer
authors.affiliation: The Centre for Research in Evidence-Based Practice (CREBP), Bond University, Gold Coast, Robina, Queensland 4226, Australia.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Glasziou
mesh_terms: D002908:Chronic Disease; D015897:Comorbidity; D003657:Decision Making; D019468:Disease Management; D004347:Drug Interactions; D006333:Heart Failure / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D017410:Practice Guidelines as Topic / Q000592:standards*; D015203:Reproducibility of Results
keywords: Comorbidity [MeSH]; Drug interactions [MeSH]; Heart failure [MeSH]; Interactions; Multimorbidity; Practice guideline [MeSH]