title: The added value of C-reactive protein measurement in diagnosing pneumonia in primary care: a meta-analysis of individual patient data.
abstract: BACKGROUND
  C-reactive protein (CRP) is increasingly being included in the diagnostic work-up for community-acquired pneumonia in primary care. Its added diagnostic value beyond signs and symptoms, however, remains unclear. We conducted a meta-analysis of individual patient data to quantify the added value of CRP measurement.
  
  
  METHODS
  We included studies of the diagnostic accuracy of CRP in adult outpatients with suspected lower respiratory tract infection. We contacted authors of eligible studies for inclusion of data and for additional data as needed. The value of adding CRP measurement to a basic signs-and-symptoms prediction model was assessed. Outcome measures were improvement in discrimination between patients with and without pneumonia in primary care and improvement in risk classification, both within the individual studies and across studies.
  
  
  RESULTS
  Authors of 8 eligible studies (n= 5308) provided their data sets. In all of the data sets, discrimination between patients with and without pneumonia improved after CRP measurement was added to the prediction model (extended model), with a mean improvement in the area under the curve of 0.075 (range 0.02-0.18). In a hypothetical cohort of 1000 patients, the proportion of patients without pneumonia correctly classified at low risk increased from 28% to 36% in the extended model, and the proportion with pneumonia correctly classified at high risk increased from 63% to 70%. The number of patients with pneumonia classified at low risk did not change (n= 4). Overall, the proportion of patients assigned to the intermediate-risk category decreased from 56% to 51%.
  
  
  CONCLUSIONS
  Adding CRP measurement to the diagnostic work-up for suspected pneumonia in primary care improved the discrimination and risk classification of patients. However, it still left a substantial group of patients classified at intermediate risk, in which clinical decision-making remains challenging.
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands m.c.minnaard@umcutrecht.nl.
authors.forename: Margaretha C
authors.initials: MC
authors.lastname: Minnaard
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Joris A H
authors.initials: JAH
authors.lastname: de Groot
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Rogier M
authors.initials: RM
authors.lastname: Hopstaken
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Alwin
authors.initials: A
authors.lastname: Schierenberg
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Niek J
authors.initials: NJ
authors.lastname: de Wit
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Johannes B
authors.initials: JB
authors.lastname: Reitsma
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Berna D L
authors.initials: BDL
authors.lastname: Broekhuizen
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Saskia F
authors.initials: SF
authors.lastname: van Vugt
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Arie Knuistingh
authors.initials: AK
authors.lastname: Neven
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Aleida W
authors.initials: AW
authors.lastname: Graffelman
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Hasse
authors.initials: H
authors.lastname: Melbye
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Rainer
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Johann
authors.initials: J
authors.lastname: Steurer
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Anette
authors.initials: A
authors.lastname: Holm
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Ralph
authors.initials: R
authors.lastname: Gonzales
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Dinant
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Alma C
authors.initials: AC
authors.lastname: van de Pol
authors.affiliation: University Medical Center Utrecht (Minnaard, de Groot, Schierenberg, de Wit, Reitsma, Broekhuizen, van Vugt, van de Pol, Verheij), Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands; Saltro Diagnostic Center for Primary Care (Hopstaken), Utrecht, the Netherlands; Department of Public Health and Primary Care (Knuistingh Neven, Graffelman), Leiden University Medical Center, Leiden, the Netherlands; Department of Community Medicine (Melbye), UiT the Arctic University of Norway, Tromsø, Norway; Chinese University of Hong Kong (Rainer), Hong Kong, China; Horten Centre for Patient Oriented Research and Knowledge Transfer (Steurer), University Zurich, Zurich, Switzerland; Department of Infectious Diseases (Holm), Odense University Hospital, Odense, Denmark; Division of General Internal Medicine (Gonzales), University of California, San Francisco, Calif.; Department of Family Medicine (Dinant), CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Theo J M
authors.initials: TJM
authors.lastname: Verheij