Biomarkers from distinct biological pathways improve early risk stratification in medical emergency patients: the multinational, prospective, observational TRIAGE study.

INTRODUCTION: Early risk stratification in the emergency department (ED) is vital to reduce time to effective treatment in high-risk patients and to improve patient flow. Yet, there is a lack of investigations evaluating the incremental usefulness of multiple biomarkers measured upon admission from distinct biological pathways for predicting fatal outcome and high initial treatment urgency in unselected ED patients in a multicenter and multinational setting. METHOD: We included consecutive, adult, medical patients seeking ED care into this observational, cohort study in Switzerland, France and the USA. We recorded initial clinical parameters and batch-measured prognostic biomarkers of inflammation (pro-adrenomedullin [ProADM]), stress (copeptin) and infection (procalcitonin). RESULTS: During a 30-day follow-up, 331 of 7132 (4.6 %) participants reached the primary endpoint of death within 30 days. In logistic regression models adjusted for conventional risk factors available at ED admission, all three biomarkers strongly predicted the risk of death (AUC 0.83, 0.78 and 0.75), ICU admission (AUC 0.67, 0.69 and 0.62) and high initial triage priority (0.67, 0.66 and 0.58). For the prediction of death, ProADM significantly improved regression models including (a) clinical information available at ED admission (AUC increase from 0.79 to 0.84), (b) full clinical information at ED discharge (AUC increase from 0.85 to 0.88), and (c) triage information (AUC increase from 0.67 to 0.83) (p <0.01 for each comparison). Similarly, ProADM also improved clinical models for prediction of ICU admission and high initial treatment urgency. Results were robust in regard to predefined patient subgroups by center, main diagnosis, presenting symptoms, age and gender. CONCLUSIONS: Combination of clinical information with results of blood biomarkers measured upon ED admission allows early and more adequate risk stratification in individual unselected medical ED patients. A randomized trial is needed to answer the question whether biomarker-guided initial patient triage reduces time to initial treatment of high-risk patients in the ED and thereby improves patient flow and clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01768494 . Registered January 9, 2013.

Optimizing triage and hospitalization in adult general medical emergency patients: the triage project.

BACKGROUND: Patients presenting to the emergency department (ED) currently face inacceptable delays in initial treatment, and long, costly hospital stays due to suboptimal initial triage and site-of-care decisions. Accurate ED triage should focus not only on initial treatment priority, but also on prediction of medical risk and nursing needs to improve site-of-care decisions and to simplify early discharge management. Different triage scores have been proposed, such as the Manchester triage system (MTS). Yet, these scores focus only on treatment priority, have suboptimal performance and lack validation in the Swiss health care system. Because the MTS will be introduced into clinical routine at the Kantonsspital Aarau, we propose a large prospective cohort study to optimize initial patient triage. Specifically, the aim of this trial is to derive a three-part triage algorithm to better predict (a) treatment priority; (b) medical risk and thus need for in-hospital treatment; (c) post-acute care needs of patients at the most proximal time point of ED admission. METHODS/DESIGN: Prospective, observational, multicenter, multi-national cohort study. We will include all consecutive medical patients seeking ED care into this observational registry. There will be no exclusions except for non-adult and non-medical patients. Vital signs will be recorded and left over blood samples will be stored for later batch analysis of blood markers. Upon ED admission, the post-acute care discharge score (PACD) will be recorded. Attending ED physicians will adjudicate triage priority based on all available results at the time of ED discharge to the medical ward. Patients will be reassessed daily during the hospital course for medical stability and readiness for discharge from the nurses and if involved social workers perspective. To assess outcomes, data from electronic medical records will be used and all patients will be contacted 30 days after hospital admission to assess vital and functional status, re-hospitalization, satisfaction with care and quality of life measures. We aim to include between 5000 and 7000 patients over one year of recruitment to derive the three-part triage algorithm. The respective main endpoints were defined as (a) initial triage priority (high vs. low priority) adjudicated by the attending ED physician at ED discharge, (b) adverse 30 day outcome (death or intensive care unit admission) within 30 days following ED admission to assess patients risk and thus need for in-hospital treatment and (c) post acute care needs after hospital discharge, defined as transfer of patients to a post-acute care institution, for early recognition and planning of post-acute care needs. Other outcomes are time to first physician contact, time to initiation of adequate medical therapy, time to social worker involvement, length of hospital stay, reasons for discharge delays, patient's satisfaction with care, overall hospital costs and patients care needs after returning home. DISCUSSION: Using a reliable initial triage system for estimating initial treatment priority, need for in-hospital treatment and post-acute care needs is an innovative and persuasive approach for a more targeted and efficient management of medical patients in the ED. The proposed interdisciplinary , multi-national project has unprecedented potential to improve initial triage decisions and optimize resource allocation to the sickest patients from admission to discharge. The algorithms derived in this study will be compared in a later randomized controlled trial against a usual care control group in terms of resource use, length of hospital stay, overall costs and patient's outcomes in terms of mortality, re-hospitalization, quality of life and satisfaction with care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01768494.

The TRIAGE-ProADM Score for an Early Risk Stratification of Medical Patients in the Emergency Department - Development Based on a Multi-National, Prospective, Observational Study.

INTRODUCTION: The inflammatory biomarker pro-adrenomedullin (ProADM) provides additional prognostic information for the risk stratification of general medical emergency department (ED) patients. The aim of this analysis was to develop a triage algorithm for improved prognostication and later use in an interventional trial. METHODS: We used data from the multi-national, prospective, observational TRIAGE trial including consecutive medical ED patients from Switzerland, France and the United States. We investigated triage effects when adding ProADM at two established cut-offs to a five-level ED triage score with respect to adverse clinical outcome. RESULTS: Mortality in the 6586 ED patients showed a step-wise, 25-fold increase from 0.6% to 4.5% and 15.4%, respectively, at the two ProADM cut-offs (≤0.75nmol/L, >0.75-1.5nmol/L, >1.5nmol/L, p ANOVA <0.0001). Risk stratification by combining ProADM within cut-off groups and the triage score resulted in the identification of 1662 patients (25.2% of the population) at a very low risk of mortality (0.3%, n = 5) and 425 patients (6.5% of the population) at very high risk of mortality (19.3%, n = 82). Risk estimation by using ProADM and the triage score from a logistic regression model allowed for a more accurate risk estimation in the whole population with a classification of 3255 patients (49.4% of the population) in the low risk group (0.3% mortality, n = 9) and 1673 (25.4% of the population) in the high-risk group (15.1% mortality, n = 252). CONCLUSIONS: Within this large international multicenter study, a combined triage score based on ProADM and established triage scores allowed a more accurate mortality risk discrimination. The TRIAGE-ProADM score improved identification of both patients at the highest risk of mortality who may benefit from early therapeutic interventions (rule in), and low risk patients where deferred treatment without negatively affecting outcome may be possible (rule out).

Predictors for Delayed Emergency Department Care in Medical Patients with Acute Infections - An International Prospective Observational Study.

INTRODUCTION: In overcrowded emergency department (ED) care, short time to start effective antibiotic treatment has been evidenced to improve infection-related clinical outcomes. Our objective was to study factors associated with delays in initial ED care within an international prospective medical ED patient population presenting with acute infections. METHODS: We report data from an international prospective observational cohort study including patients with a main diagnosis of infection from three tertiary care hospitals in Switzerland, France and the United States (US). We studied predictors for delays in starting antibiotic treatment by using multivariate regression analyses. RESULTS: Overall, 544 medical ED patients with a main diagnosis of acute infection and antibiotic treatment were included, mainly pneumonia (n = 218; 40.1%), urinary tract (n = 141; 25.9%), and gastrointestinal infections (n = 58; 10.7%). The overall median time to start antibiotic therapy was 214 minutes (95% CI: 199, 228), with a median length of ED stay (ED LOS) of 322 minutes (95% CI: 308, 335). We found large variations of time to start antibiotic treatment depending on hospital centre and type of infection. The diagnosis of a gastrointestinal infection was the most significant predictor for delay in antibiotic treatment (+119 minutes compared to patients with pneumonia; 95% CI: 58, 181; p<0.001). CONCLUSIONS: We found high variations in hospital ED performance in regard to start antibiotic treatment. The implementation of measures to reduce treatment times has the potential to improve patient care.

Unscheduled return visits to the emergency department: consequences for triage.

OBJECTIVES: The objective was to conduct a survey of unscheduled revisits (URs) to the emergency department (ED) within 8 days of a prior visit, to test the hypothesis that patients making these URs are disproportionately likely to suffer short-term mortality or manifest a need for any admission to the hospital (adverse events [AEs]) at the time of the UR, compared to patients triaged at the same level who did not have an unscheduled ED revisit within 8 days. METHODS: This was a 1-year retrospective study of patients with an UR to the ED of an urban, 1,600-bed tertiary care center and teaching hospital. The criteria for inclusion as an UR were: 1) making an emergency visit to our adult ED during 2008, without being admitted to our hospital nor being transferred to another hospital; and 2) subsequently making an UR to the same ED within 8 days following the first one. Patients who were contacted by members of our staff and specifically asked to make return visits to our ED (such as those who returned for wound care follow-up visits), and those who made more than five visits to our ED during 2008, were excluded. AEs were defined as death or hospitalization within 8 days of the second visit. RESULTS: During 2008, there were 946 patients with URs (2% of patients treated and released after the first ED visit), and 931 were analyzed (n = 15 missing values). Associated with the second visit, an AE was noted for 276 (30%) patients. Eight variables were significantly associated with AE: age ≥ 65 years, previously diagnosed cancer, previously diagnosed cardiac disease, previously diagnosed psychiatric disease, presence of a relative at the time of the UR, arrival with a letter from a general practitioner at the time of the UR, a higher level of severity assigned at triage for the UR than for the first ED visit, and having had blood sample analysis performed during the first visit. The median triage score for the UR was not significantly different from that group's median triage score for the first ED visit, whereas the proportion of admissions to the hospital (29%) or to the intensive care unit (ICU; 2%) was greater overall in the UR group than in the patients making their first ED visit. CONCLUSIONS: The authors observed that 2% of patients had an UR. This UR population was at greater risk of AE at the time of their URs compared to their initial visits, but the median triage nurse score was not significantly different between the first visit and the UR. This suggests that the triage score should be systematically upgraded for UR patients.