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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

Saeed, Kordo ; Wilson, Darius Cameron ; Bloos, Frank ; Schuetz, Philipp ; Van Der Does, Yuri ; Melander, Olle LU orcid ; Hausfater, Pierre ; Legramante, Jacopo M. ; Claessens, Yann Erick and Amin, Deveendra , et al. (2019) In Critical Care 23(1).
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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Disease progression, Emergency department, MR-proADM, qSOFA, Sepsis, SOFA
in
Critical Care
volume
23
issue
1
article number
40
publisher
BioMed Central (BMC)
external identifiers
  • pmid:30736862
  • scopus:85061258269
ISSN
1364-8535
DOI
10.1186/s13054-019-2329-5
language
English
LU publication?
yes
id
36922e33-cd05-405b-b3a7-b15b44297ae7
date added to LUP
2019-02-19 08:04:46
date last changed
2024-04-01 22:15:07
@article{36922e33-cd05-405b-b3a7-b15b44297ae7,
  abstract     = {{<p>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 &gt; 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 &lt; 0.25 ng/mL, lactate &lt; 2.0 mmol/L or CRP &lt; 67 mg/L) or clinical score (SOFA &lt; 2 points, qSOFA &lt; 2 points, NEWS &lt; 4 points or CRB-65 &lt; 2 points) values were characterised by a significantly longer length of hospitalisation (p &lt; 0.001), rate of ICU admission (p &lt; 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 &lt; 0.001), compared to similar subgroups with low MR-proADM concentrations (&lt; 1.54 nmol/L). Increased out-patient treatment across both cohorts could be facilitated using a derivation-derived MR-proADM cut-off of &lt; 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.</p>}},
  author       = {{Saeed, Kordo and Wilson, Darius Cameron and Bloos, Frank and Schuetz, Philipp and Van Der Does, Yuri and Melander, Olle and Hausfater, Pierre and Legramante, Jacopo M. and Claessens, Yann Erick and Amin, Deveendra and Rosenqvist, Mari and White, Graham and Mueller, Beat and Limper, Maarten and Callejo, Carlota Clemente and Brandi, Antonella and MacChi, Marc Alexis and Cortes, Nicholas and Kutz, Alexander and Patka, Peter and Yañez, María Cecilia and Bernardini, Sergio and Beau, Nathalie and Dryden, Matthew and Van Gorp, Eric C.M. and Minieri, Marilena and Chan, Louisa and Rood, Pleunie P.M. and Del Castillo, Juan Gonzalez}},
  issn         = {{1364-8535}},
  keywords     = {{Disease progression; Emergency department; MR-proADM; qSOFA; Sepsis; SOFA}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Critical Care}},
  title        = {{The early identification of disease progression in patients with suspected infection presenting to the emergency department : A multi-centre derivation and validation study}},
  url          = {{http://dx.doi.org/10.1186/s13054-019-2329-5}},
  doi          = {{10.1186/s13054-019-2329-5}},
  volume       = {{23}},
  year         = {{2019}},
}