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The early identification of disease progression in patients with suspected infection presenting to the emergency department: a multi-centre derivation and validation study

The early identification of disease progression in patients with suspected infection presenting to the emergency department: a multi-centre derivation and validation study
The early identification of disease progression in patients with suspected infection presenting to the emergency department: a multi-centre derivation and validation study

Background: There is a lack of validated tools to assess potential disease progression and hospitalisation decisions in patients presenting to the emergency department (ED) with a suspected infection. This study aimed to identify suitable blood biomarkers (MR-proADM, PCT, lactate and CRP) or clinical scores (SIRS, SOFA, qSOFA, NEWS and CRB-65) to fulfil this unmet clinical need. Methods: An observational derivation patient cohort validated by an independent secondary analysis across nine EDs. Logistic and Cox regression, area under the receiver operating characteristic (AUROC) and Kaplan-Meier curves were used to assess performance. Disease progression was identified using a composite endpoint of 28-day mortality, ICU admission and hospitalisation > 10 days. Results: One thousand one hundred seventy-five derivation and 896 validation patients were analysed with respective 28-day mortality rates of 7.1% and 5.0%, and hospitalisation rates of 77.9% and 76.2%. MR-proADM showed greatest accuracy in predicting 28-day mortality and hospitalisation requirement across both cohorts. Patient subgroups with high MR-proADM concentrations (≥ 1.54 nmol/L) and low biomarker (PCT < 0.25 ng/mL, lactate < 2.0 mmol/L or CRP < 67 mg/L) or clinical score (SOFA < 2 points, qSOFA < 2 points, NEWS < 4 points or CRB-65 < 2 points) values were characterised by a significantly longer length of hospitalisation (p < 0.001), rate of ICU admission (p < 0.001), elevated mortality risk (e.g. SOFA, qSOFA and NEWS HR [95%CI], 45.5 [10.0-207.6], 23.4 [11.1-49.3] and 32.6 [9.4-113.6], respectively) and a greater number of disease progression events (p < 0.001), compared to similar subgroups with low MR-proADM concentrations (< 1.54 nmol/L). Increased out-patient treatment across both cohorts could be facilitated using a derivation-derived MR-proADM cut-off of < 0.87 nmol/L (15.0% and 16.6%), with decreased readmission rates and no mortalities. Conclusions: In patients presenting to the ED with a suspected infection, the blood biomarker MR-proADM could most accurately identify the likelihood of further disease progression. Incorporation into an early sepsis management protocol may therefore aid rapid decision-making in order to either initiate, escalate or intensify early treatment strategies, or identify patients suitable for safe out-patient treatment.

Disease progression, Emergency department, MR-proADM, qSOFA, Sepsis, SOFA
1364-8535
1-15
Saeed, Kordo
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Wilson, Darius Cameron
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Bloos, Frank
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Schuetz, Philipp
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Van Der Does, Yuri
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Melander, Olle
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Hausfater, Pierre
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Legramante, Jacopo M.
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Claessens, Yann Erick
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Amin, Deveendra
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Rosenqvist, Mari
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White, Graham
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Mueller, Beat
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Limper, Maarten
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Callejo, Carlota Clemente
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Brandi, Antonella
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MacChi, Marc Alexis
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Cortes, Nicholas
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Kutz, Alexander
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Patka, Peter
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Yañez, María Cecilia
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Bernardini, Sergio
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Beau, Nathalie
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Dryden, Matthew
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Van Gorp, Eric C.M.
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Minieri, Marilena
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Chan, Louisa
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Rood, Pleunie P.M.
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Del Castillo, Juan Gonzalez
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Saeed, Kordo
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Wilson, Darius Cameron
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Bloos, Frank
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Schuetz, Philipp
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Van Der Does, Yuri
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Melander, Olle
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Hausfater, Pierre
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Legramante, Jacopo M.
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Claessens, Yann Erick
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Amin, Deveendra
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Rosenqvist, Mari
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White, Graham
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Mueller, Beat
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Limper, Maarten
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Callejo, Carlota Clemente
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Brandi, Antonella
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MacChi, Marc Alexis
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Cortes, Nicholas
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Kutz, Alexander
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Patka, Peter
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Yañez, María Cecilia
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Bernardini, Sergio
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Beau, Nathalie
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Dryden, Matthew
28a2efa7-1f6a-4260-a05b-284448c248fc
Van Gorp, Eric C.M.
c861cc0e-45dd-4e5b-865a-dd423a893859
Minieri, Marilena
a0c64a46-d2ba-4b17-912a-5b0f498776f0
Chan, Louisa
fef8f72f-038a-4a65-b514-93bc2f97a7fd
Rood, Pleunie P.M.
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Del Castillo, Juan Gonzalez
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Saeed, Kordo, Wilson, Darius Cameron, Bloos, Frank, Schuetz, Philipp, Van Der Does, Yuri, Melander, Olle, Hausfater, Pierre, Legramante, Jacopo M., Claessens, Yann Erick, Amin, Deveendra, Rosenqvist, Mari, White, Graham, Mueller, Beat, Limper, Maarten, Callejo, Carlota Clemente, Brandi, Antonella, MacChi, Marc Alexis, Cortes, Nicholas, Kutz, Alexander, Patka, Peter, Yañez, María Cecilia, Bernardini, Sergio, Beau, Nathalie, Dryden, Matthew, Van Gorp, Eric C.M., Minieri, Marilena, Chan, Louisa, Rood, Pleunie P.M. and Del Castillo, Juan Gonzalez (2019) The early identification of disease progression in patients with suspected infection presenting to the emergency department: a multi-centre derivation and validation study. Critical Care, 23 (1), 1-15. (doi:10.1186/s13054-019-2329-5).

Record type: Article

Abstract

Background: There is a lack of validated tools to assess potential disease progression and hospitalisation decisions in patients presenting to the emergency department (ED) with a suspected infection. This study aimed to identify suitable blood biomarkers (MR-proADM, PCT, lactate and CRP) or clinical scores (SIRS, SOFA, qSOFA, NEWS and CRB-65) to fulfil this unmet clinical need. Methods: An observational derivation patient cohort validated by an independent secondary analysis across nine EDs. Logistic and Cox regression, area under the receiver operating characteristic (AUROC) and Kaplan-Meier curves were used to assess performance. Disease progression was identified using a composite endpoint of 28-day mortality, ICU admission and hospitalisation > 10 days. Results: One thousand one hundred seventy-five derivation and 896 validation patients were analysed with respective 28-day mortality rates of 7.1% and 5.0%, and hospitalisation rates of 77.9% and 76.2%. MR-proADM showed greatest accuracy in predicting 28-day mortality and hospitalisation requirement across both cohorts. Patient subgroups with high MR-proADM concentrations (≥ 1.54 nmol/L) and low biomarker (PCT < 0.25 ng/mL, lactate < 2.0 mmol/L or CRP < 67 mg/L) or clinical score (SOFA < 2 points, qSOFA < 2 points, NEWS < 4 points or CRB-65 < 2 points) values were characterised by a significantly longer length of hospitalisation (p < 0.001), rate of ICU admission (p < 0.001), elevated mortality risk (e.g. SOFA, qSOFA and NEWS HR [95%CI], 45.5 [10.0-207.6], 23.4 [11.1-49.3] and 32.6 [9.4-113.6], respectively) and a greater number of disease progression events (p < 0.001), compared to similar subgroups with low MR-proADM concentrations (< 1.54 nmol/L). Increased out-patient treatment across both cohorts could be facilitated using a derivation-derived MR-proADM cut-off of < 0.87 nmol/L (15.0% and 16.6%), with decreased readmission rates and no mortalities. Conclusions: In patients presenting to the ED with a suspected infection, the blood biomarker MR-proADM could most accurately identify the likelihood of further disease progression. Incorporation into an early sepsis management protocol may therefore aid rapid decision-making in order to either initiate, escalate or intensify early treatment strategies, or identify patients suitable for safe out-patient treatment.

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Accepted/In Press date: 18 January 2019
Published date: 8 February 2019
Keywords: Disease progression, Emergency department, MR-proADM, qSOFA, Sepsis, SOFA

Identifiers

Local EPrints ID: 428272
URI: https://eprints.soton.ac.uk/id/eprint/428272
ISSN: 1364-8535
PURE UUID: f5073884-68d8-4a9d-a43b-70bc7e223c1b

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Date deposited: 20 Feb 2019 17:30
Last modified: 09 Dec 2019 17:43

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Contributors

Author: Kordo Saeed
Author: Darius Cameron Wilson
Author: Frank Bloos
Author: Philipp Schuetz
Author: Yuri Van Der Does
Author: Olle Melander
Author: Pierre Hausfater
Author: Jacopo M. Legramante
Author: Yann Erick Claessens
Author: Deveendra Amin
Author: Mari Rosenqvist
Author: Graham White
Author: Beat Mueller
Author: Maarten Limper
Author: Carlota Clemente Callejo
Author: Antonella Brandi
Author: Marc Alexis MacChi
Author: Nicholas Cortes
Author: Alexander Kutz
Author: Peter Patka
Author: María Cecilia Yañez
Author: Sergio Bernardini
Author: Nathalie Beau
Author: Matthew Dryden
Author: Eric C.M. Van Gorp
Author: Marilena Minieri
Author: Louisa Chan
Author: Pleunie P.M. Rood
Author: Juan Gonzalez Del Castillo

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