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Revisiting the effect of referral bias on the clinical spectrum of infective endocarditis in adults

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Abstract

Referral bias occurs because of the clustering of patients at tertiary care centers. This may result in the distortion of observed clinical manifestations of rare diseases. This analysis evaluates the effect of referral bias on the epidemiology of infective endocarditis (IE) in the International Collaboration on Endocarditis—Prospective Cohort Study (ICE-PCS). This is a prospective multicenter cohort study comparing transferred and non-transferred patients with IE. Factors independently associated with transfer status were evaluated using multivariable logistic regression. A total of 2,760 patients were included in the analysis, of which 1,164 (42.2%) were transferred from other medical centers. Transferred patients more often underwent surgery for IE (odds ratio [OR] = 2.5; 95% confidence interval [CI] 1.9–3.2). They were also more likely to have complications such as stroke (OR = 1.5; 95% CI 1.3–1.9), heart failure (OR = 1.4; 95% CI 1.1–1.6), and new valvular regurgitation (OR = 1.3; 95% CI 1.1–1.6). The in-hospital mortality rates were similar in both groups. Patients with IE who require surgery and suffer complications are referred to tertiary hospitals more frequently than patients with an uncomplicated course. Hospital transfer has no obvious effect on the in-hospital mortality. Referral bias should be taken into consideration when describing the clinical spectrum of IE.

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Acknowledgments

The following investigators are members of the ICE-PCS: David Gordon, Uma Devi (Flinders Medical Centre, Adelaide, Australia); Denis Spelman (Alfred Hospital, Amiens, France); Jan van der Meer (University of Amsterdam, Amsterdam, Netherlands); Carol Kauffman, Suzanne Bradley, William Armstrong (Ann Arbor VA Medical Center, Ann Arbor, USA); Efthymia Giannitsioti, Helen Giamarellou (Attikon University General Hospital, Athens, Greece); Stamatios Lerakis (Emory University, Atlanta, USA); Ana del Rio, Asuncion Moreno, Carlos Mestres, Carlos Paré, Cristina Garcia de la Maria, Elisa De Lazzario, Francesc Marco, Jose Gatell, José Miró, Manel Almela, Manuel Azqueta, Maria Jesús Jiménez-Expósito, Natividad de Benito, Noel Perez (Hosp. Clinic—IDIBAPS: University of Barcelona, Barcelona, Spain); Benito Almirante, Nuria Fernandez-Hidalgo, Pablo Rodriguez de Vera, Pilar Tornos, Vicente Falcó, Xavier Claramonte, Yolanda Armero (Hospital Universitari Vall d’Hebron, Barcelona, Spain); Souha Kanj, Zeina Kanafani (American University of Beirut Medical Center, Beirut, Lebanon); Annibale Raglio, Antonio Goglio, Fabrizio Gnecchi, Fredy Suter, Grazia Valsecchi, Marco Rizzi, Veronica Ravasio (Ospedali Riuniti di Bergamo, Bergamo, Italy); Bruno Hoen, Catherine Chirouze, Efthymia Giannitsioti, Joel Leroy, Patrick Plesiat, Yvette Bernard (University Medical Center of Besançon, Besançon, France); Anna Casey, Peter Lambert, Richard Watkin, Tom Elliott (Queen Elizabeth Hospital, Birmingham, UK); Mukesh Patel, William Dismukes (University of Alabama at Birmingham, Birmingham, USA); Angelo Pan, Giampiero Caros (Spedali Civili—Università di Brescia, Brescia, Italy); Amel Brahim Mathiron, Christophe Tribouilloy, Thomas Goissen (South Hospital Amiens, Bron Cedex, France); Armelle Delahaye, Francois Delahaye, Francois Vandenesch (Hopital Louis Pradel, Bron Cedex, France); Carla Vizzotti, Francisco Nacinovich, Marcelo Marin, Marcelo Trivi, Martin Lombardero (Instituto Cardiovascular, Buenos Aires, Argentina); Claudia Cortes, José Horacio Casabé (Instituto de Cardiología y Cirugía Cardiovascular, Buenos Aires, Argentina); Javier Altclas, Silvia Kogan (Sanatorio Mitre, Buenos Aires, Argentina); Liliana Clara, Marisa Sanchez (Hospital Italiano, Buenos Aires, Argentina); Anita Commerford, Cass Hansa, Eduan Deetlefs, Mpiko Ntsekhe, Patrick Commerford (Groote Schuur Hospital, Cape Town, South Africa); Dannah Wray, Lisa Steed, Preston Church, Robert Cantey (Medical University of South Carolina, Charleston, USA); Arthur Morris, David Holland, David Murdoch, Katherine Graham, Kerry Read, Nigel Raymond, Paul Bridgman, Richard Troughton, Selwyn Lang, Stephen Chambers (Canterbury Health Laboratories, Christchurch, New Zealand); Despina Kotsanas, Tony Korman (Southern Health, Clayton, Australia); Gail Peterson, Jon Purcell, Paul Southern, Jr. (UT-Southwestern Medical Center, Dallas, USA); Manisha Shah, Roger Bedimo (Dallas VA Medical Center, Dallas, USA); Arjun Reddy, Donald Levine, Gaurav Dhar (Wayne State University, Detroit, USA); Alanna Hanlon-Feeney, Margaret Hannan, Sinead Kelly (Mater Hospitals, Dublin, Ireland); Andrew Wang, Christopher Cabell, Christopher Woods, Daniel Sexton, Danny Benjamin, Jr., Ralph Corey, Jeff Federspiel, Barth Reller, Laura Drew, Khaula Baloch, Tina Harding, Vance Fowler, Jr., Vivian Chu (Duke University Medical Center, Durham, USA); Bahram Mazaheri, Carl Neuerburg, Christoph Naber (University Essen, Essen, Germany); Eugene Athan, Margaret Henry, Owen Harris (Barwon Health, Geelong, Australia); Eric Alestig, Lars Olaison, Lotta Wikstrom, Ulrika Snygg-Martin (Sahlgrenska Universitetssjukhuset/Östra, Goteborg, Sweden); Johnson Francis, K Venugopal, Lathi Nair, Vinod Thomas (Medical College Calicut, Kerla, India); Jaruwan Chaiworramukkun, Orathai Pachirat, Ploenchan Chetchotisakd, Tewan Suwanich (Khon Kaen University, Khon Kaen, Thailand); Adeeba Kamarulzaman, Syahidah Syed Tamin (University of Malaya Medical Center, Kuala Lumpur, Malaysia); Manica Mueller Premru, Mateja Logar, Tatjana Lejko-Zupanc (Medical Center Ljublijana, Ljublijana, Slovenia); Christina Orezzi, John Klein (St. Thomas’ Hospital, London, UK); Emilio Bouza, Mar Moreno, Marta Rodríguez-Créixems, Mercedes Marín, Miguel Fernández, Patricia Muñoz, Rocío Fernández, Victor Ramallo (Hospital General Universitario Gregorio Marañón, Madrid, Spain); Didier Raoult, Franck Thuny, Gilbert Habib, Jean-Paul Casalta, Pierre-Edouard Fournier (Faculté de Médecine de Marseille, Marseille, France); Natalia Chipigina, Ozerecky Kirill, Tatiana Vinogradova, Vadim Kulichenko (Russian Medical State University, Moscow, Russia); OM Butkevich (Learning Medical Centre of Russian Presidential Affairs Government, Moscow, Russia); Christine Lion, Christine Selton-Suty, Francois Alla, Hélène Coyard, Thanh Doco-Lecompte (CHU Nancy-Brabois, Nancy, France); Diana Iarussi, Emanuele Durante-Mangoni, Marie Françoise Tripodi, Riccardo Utili (II Università di Napoli, Naples, Italy); Sampath Kumar, Gautam Sharma (All India Institute of Medical Sciences, New Delhi, India); Stuart Dickerman (New York University Medical Center, New York, USA); Alan Street, Damon Peter Eisen, Emma Sue McBryde, Leeanne Grigg (Royal Melbourne Hospital, Parkville, Australia); Elias Abrutyn (Drexel University College of Medicine, Philadelphia, USA); Christian Michelet, Pierre Tattevin, Pierre Yves Donnio (Pontchaillou University, Rennes, France); Claudio Querido Fortes (Hospital Universitario Clementino Fraga Filho/UFRJ, Rio de Janeiro, Brazil); Jameela Edathodu (King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia); Bernat Font, Ignasi Anguera, Joan Raimon Guma (Hospitál de Sabadell, Sabedell, Spain); M Cereceda, Miguel Oyonarte, Rodrigo Montagna Mella (Hospital Clinico Universidad de Chile, Santiago, Chile); Patricia Garcia, Sandra Braun Jones (Hosp. Clínico Pont. Universidad Católica de Chile, Santiago, Chile); Auristela Isabel de Oliveira Ramos (Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil); Marcelo Goulart Paiva, Regina Aparecida de Medeiros Tranchesi (Hospital 9 de Julho, São Paulo, Brazil); Lok Ley Woon, Luh-Nah LumN, Ru-San Tan (National Heart Centre, Singapore, Singapore); David Rees, Pam Kornecny, Richard Lawrence, Robyn Dever (St. George Hospital, Sydney, Australia); Jeffrey Post, Phillip Jones, Suzanne Ryan, GCDM (The University of New South Wales, Sydney, Australia); John Harkness, Michael Feneley (St. Vincent’s, Sydney, Australia); Ethan Rubinstein, Jacob Strahilewitz (Tel Aviv University School of Medicine, Tel Aviv, Israel); Adina Ionac, Cristian Mornos, Stefan Dragulescu (Victor Babes University of Medicine and Pharmacy, Timisoar, Romania); Davide Forno, Enrico Cecchi, Francesco De Rosa, Massimo Imazio, Rita Trinchero (Maria Vittoria Hospital, Torino, Italy); Franz Wiesbauer, Rainer Gattringer (Vienna General Hospital, Vienna, Austria); Ethan Rubinstein, Greg Deans (University of Manitoba, Winnipeg, Canada); Arjana Tambic Andrasevic, Bruno Barsic, Igor Klinar, Josip Vincelj, Suzana Bukovski, Vladimir Krajinovic (Univ. Hospital for Infectious Diseases, Zagreb, Croatia).

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Authors and Affiliations

  1. American University of Beirut Medical Center, Beirut, Lebanon

    Z. A. Kanafani & S. S. Kanj

  2. Duke University Medical Center, Durham, NC, USA

    C. H. Cabell, A. Wang & D. J. Sexton

  3. Duke Clinical Research Institute, Durham, NC, USA

    C. H. Cabell & P. A. Pappas

  4. Maria Vittoria Hospital, Turin, Italy

    E. Cecchi

  5. Instituto Dante Pazzanese de Cardiologia, Moema, Brazil

    A. de Oliveira Ramos

  6. Medical Center Ljubljana, Ljubljana, Slovenia

    T. Lejko-Zupanc

  7. Attikon University General Hospital, Athens, Greece

    H. Giamerellou

  8. Flinders Medical Centre, Adelaide, Australia

    D. Gordon

  9. Pontchaillou University, Rennes, France

    C. Michelet & P. Tattevin

  10. Hospital General Universitario Gregorio Marañón, Madrid, Spain

    P. Muñoz

  11. Khon Kaen University, Khon Kaen, Thailand

    O. Pachirat

  12. University of Texas Southwestern Medical Center, Dallas, TX, USA

    G. Peterson

  13. National Heart Centre, Singapore, Singapore

    R.-S. Tan

  14. Medical College Calicut, Kerala, India

    V. Thomas

  15. Vienna General Hospital, Vienna, Austria

    F. Wiesbauer

  16. Division of Infectious Diseases, Hospital Epidemiologist, American University of Beirut Medical Center, Cairo Street, P.O. Box 11-0236/11D, Riad El Solh, 1107 2020, Beirut, Lebanon

    Z. A. Kanafani

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  1. Z. A. Kanafani
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  2. S. S. Kanj
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  3. C. H. Cabell
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  4. E. Cecchi
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  5. A. de Oliveira Ramos
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  6. T. Lejko-Zupanc
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  7. P. A. Pappas
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  8. H. Giamerellou
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  9. D. Gordon
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  10. C. Michelet
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  11. P. Muñoz
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  12. O. Pachirat
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  13. G. Peterson
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  14. R.-S. Tan
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  15. P. Tattevin
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  16. V. Thomas
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  17. A. Wang
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  18. F. Wiesbauer
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  19. D. J. Sexton
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Correspondence to Z. A. Kanafani.

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Kanafani, Z.A., Kanj, S.S., Cabell, C.H. et al. Revisiting the effect of referral bias on the clinical spectrum of infective endocarditis in adults. Eur J Clin Microbiol Infect Dis 29, 1203–1210 (2010). https://doi.org/10.1007/s10096-010-0983-2

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  • DOI: https://doi.org/10.1007/s10096-010-0983-2

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