Research
The added value of C-reactive protein measurement in diagnosing pneumonia in primary care: a meta-analysis of individual patient data
Margaretha C. Minnaard, Joris A.H. de Groot, Rogier M. Hopstaken, Alwin Schierenberg, Niek J. de Wit, Johannes B. Reitsma, Berna D.L. Broekhuizen, Saskia F. van Vugt, Arie Knuistingh Neven, Aleida W. Graffelman, Hasse Melbye, Timothy H. Rainer, Johann Steurer, Anette Holm, Ralph Gonzales, Geert-Jan Dinant, Alma C. van de Pol and Theo J.M. Verheij
CMAJ January 16, 2017 189 (2) E56-E63; DOI: https://doi.org/10.1503/cmaj.151163
Margaretha C. Minnaard
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
MDJoris A.H. de Groot
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
PhDRogier M. Hopstaken
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
MD PhDAlwin Schierenberg
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
MDNiek J. de Wit
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
MD PhDJohannes B. Reitsma
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
MD PhDBerna D.L. Broekhuizen
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
MD PhDSaskia F. van Vugt
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
MD PhDArie Knuistingh Neven
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
MD PhDAleida W. Graffelman
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
MD PhDHasse Melbye
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
MD PhDTimothy H. Rainer
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
MD PhDJohann Steurer
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
MD PhDAnette Holm
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
MD PhDRalph Gonzales
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
MD MSPHGeert-Jan Dinant
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
MD PhDAlma C. van de Pol
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
MD PhDTheo J.M. Verheij
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
MD PhDData supplements
Online Appendices
- Appendix 1: Search strategy PubMed, EMBASE, Cochrane Library
- Appendix 2: Missing values (%) of the pre-specified signs & symptoms and CRP in the 8 individual patient datasets
- Appendix 3: Basic and extended models
- Appendix 4: Table of characteristics of excluded studies
- Appendix 5: Overview of methodological quality. Methodological quality of included validation datasets according to QUADAS-2 assessment
- Appendix 6: Reclassification table illustrating the improved diagnostic risk classification after adding CRP to the diagnostic work-up of patients suspected of CAP in a hypothetical cohort of 1000 patients, based on a relatively low CAP prevalence of 5%
- Appendix 7: Reclassification table illustrating the improved diagnostic risk classification after adding CRP to the diagnostic work-up of patients suspected of CAP in a hypothetical cohort of 1000 patients, based on a relatively high CAP prevalence of 20
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The added value of C-reactive protein measurement in diagnosing pneumonia in primary care: a meta-analysis of individual patient data
Margaretha C. Minnaard, Joris A.H. de Groot, Rogier M. Hopstaken, Alwin Schierenberg, Niek J. de Wit, Johannes B. Reitsma, Berna D.L. Broekhuizen, Saskia F. van Vugt, Arie Knuistingh Neven, Aleida W. Graffelman, Hasse Melbye, Timothy H. Rainer, Johann Steurer, Anette Holm, Ralph Gonzales, Geert-Jan Dinant, Alma C. van de Pol, Theo J.M. Verheij
CMAJ Jan 2017, 189 (2) E56-E63; DOI: 10.1503/cmaj.151163
The added value of C-reactive protein measurement in diagnosing pneumonia in primary care: a meta-analysis of individual patient data
Margaretha C. Minnaard, Joris A.H. de Groot, Rogier M. Hopstaken, Alwin Schierenberg, Niek J. de Wit, Johannes B. Reitsma, Berna D.L. Broekhuizen, Saskia F. van Vugt, Arie Knuistingh Neven, Aleida W. Graffelman, Hasse Melbye, Timothy H. Rainer, Johann Steurer, Anette Holm, Ralph Gonzales, Geert-Jan Dinant, Alma C. van de Pol, Theo J.M. Verheij
CMAJ Jan 2017, 189 (2) E56-E63; DOI: 10.1503/cmaj.151163
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