Background: There is a lack of validated tools to assess potential disease progression and hospitalisation decisions\nin patients presenting to the emergency department (ED) with a suspected infection. This study aimed to identify\nsuitable blood biomarkers (MR-proADM, PCT, lactate and CRP) or clinical scores (SIRS, SOFA, qSOFA, NEWS and CRB-\n65) to fulfil this unmet clinical need.\nMethods: An observational derivation patient cohort validated by an independent secondary analysis across nine\nEDs. Logistic and Cox regression, area under the receiver operating characteristic (AUROC) and Kaplan-Meier curves\nwere used to assess performance. Disease progression was identified using a composite endpoint of 28-day mortality, ICU\nadmission and hospitalisation > 10 days.\nResults: One thousand one hundred seventy-five derivation and 896 validation patients were analysed with respective\n28-day mortality rates of 7.1% and 5.0%, and hospitalisation rates of 77.9% and 76.2%. MR-proADM showed greatest\naccuracy in predicting 28-day mortality and hospitalisation requirement across both cohorts. Patient subgroups with high\nMR-proADM concentrations (less than equal to 1.54 nmol/L) and low biomarker (PCT < 0.25 ng/mL, lactate < 2.0mmol/L or CRP < 67 mg/\nL) or clinical score (SOFA < 2 points, qSOFA < 2 points, NEWS < 4 points or CRB-65 < 2 points) values were characterised\nby a significantly longer length of hospitalisation (p < 0.001), rate of ICU admission (p < 0.001), elevated mortality risk (e.g.\nSOFA, 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\nnumber of disease progression events (p < 0.001), compared to similar subgroups with low MR-proADM concentrations\n(< 1.54 nmol/L). Increased out-patient treatment across both cohorts could be facilitated using a derivation-derived MRproADM\ncut-off of < 0.87 nmol/L (15.0% and 16.6%), with decreased readmission rates and no mortalities.
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