The growing number of older patients presenting to Emergency Departments (EDs) requires better risk stratification to guide treatment and dispositiondecisions. Therefore, it is essential to... Show moreThe growing number of older patients presenting to Emergency Departments (EDs) requires better risk stratification to guide treatment and dispositiondecisions. Therefore, it is essential to understand the effect of age on the associations between physiological variables and outcomes. More importantly, most risk tools are not age or sex adjusted and are not based on a statistical approach. An age and sex adjusted risk tool could improve risk stratification in the ED.This thesis is divided into three parts and has four aims, regarding ageadjusted interpretation of physiological variables for risk stratification in ED patients, developing a new age- and sex-adjusted risk tool for the hospital, and describing potential bias if risk tools are used for comparing the quality of care among departments. Show less
Candel, B.G.J.; Raven, W.; Nissen, S.K.; Morsink, M.E.B.; Gaakeer, M.I.; Brabrand, M.; ... ; Groot, B. de 2023
BackgroundGuidelines and textbooks assert that tachycardia is an early and reliable sign of hypotension, and an increased heart rate (HR) is believed to be an early warning sign for the development... Show moreBackgroundGuidelines and textbooks assert that tachycardia is an early and reliable sign of hypotension, and an increased heart rate (HR) is believed to be an early warning sign for the development of shock, although this response may change by aging, pain, and stress.ObjectiveTo assess the unadjusted and adjusted associations between systolic blood pressure (SBP) and HR in emergency department (ED) patients of different age categories (18–50 years; 50–80 years; > 80 years).MethodsA multicenter cohort study using the Netherlands Emergency department Evaluation Database (NEED) including all ED patients ≥ 18 years from three hospitals in whom HR and SBP were registered at arrival to the ED. Findings were validated in a Danish cohort including ED patients. In addition, a separate cohort was used including ED patients with a suspected infection who were hospitalized from whom measurement of SBP and HR were available prior to, during, and after ED treatment. Associations between SBP and HR were visualized and quantified with scatterplots and regression coefficients (95% confidence interval [CI]).ResultsA total of 81,750 ED patients were included from the NEED, and a total of 2358 patients with a suspected infection. No associations were found between SBP and HR in any age category (18–50 years: −0.03 beats/min/10 mm Hg, 95% CI −0.13–0.07, 51–80 years: −0.43 beats/min/10 mm Hg, 95% CI −0.38 to −0.50, > 80 years: −0.61 beats/min/10 mm Hg, 95% CI −0.53 to −0.71), nor in different subgroups of ED patient. No increase in HR existed with a decreasing SBP during ED treatment in ED patients with a suspected infection.ConclusionNo association between SBP and HR existed in ED patients of any age category, nor in ED patients who were hospitalized with a suspected infection, even during and after ED treatment. Emergency physicians may be misled by traditional concepts about HR disturbances because tachycardia may be absent in hypotension. Show less
Candel, B.G.J.; Nissen, S.K.; Nickel, C.H.; Raven, W.; Thijssen, W.; Gaakeer, M.I.; ... ; Groot, B. de 2023
Objectives: Early Warning Scores (EWSs) have a great potential to assist clinical decision-making in the emergency department (ED). However, many EWS contain methodological weaknesses in... Show moreObjectives: Early Warning Scores (EWSs) have a great potential to assist clinical decision-making in the emergency department (ED). However, many EWS contain methodological weaknesses in development and validation and have poor predictive performance in older patients. The aim of this study was to develop and externally validate an International Early Warning Score (IEWS) based on a recalibrated National Early warning Score (NEWS) model including age and sex and evaluate its performance independently at arrival to the ED in three age categories (18–65, 66–80, > 80 yr).Design: International multicenter cohort study.Setting: Data was used from three Dutch EDs. External validation was performed in two EDs in Denmark.Patients: All consecutive ED patients greater than or equal to 18 years in the Netherlands Emergency department Evaluation Database (NEED) with at least two registered vital signs were included, resulting in 95,553 patients. For external validation, 14,809 patients were included from a Danish Multicenter Cohort (DMC).Measurements and Main Results: Model performance to predict in-hospital mortality was evaluated by discrimination, calibration curves and summary statistics, reclassification, and clinical usefulness by decision curve analysis. In-hospital mortality rate was 2.4% (n = 2,314) in the NEED and 2.5% (n = 365) in the DMC. Overall, the IEWS performed significantly better than NEWS with an area under the receiving operating characteristic of 0.89 (95% CIs, 0.89–0.90) versus 0.82 (0.82–0.83) in the NEED and 0.87 (0.85–0.88) versus 0.82 (0.80–0.84) at external validation. Calibration for NEWS predictions underestimated risk in older patients and overestimated risk in the youngest, while calibration improved for IEWS with a substantial reclassification of patients from low to high risk and a standardized net benefit of 5–15% in the relevant risk range for all age categories.Conclusions: The IEWS substantially improves in-hospital mortality prediction for all ED patients greater than or equal to18 years. Show less
Candel, B.G.J.; Raven, W.; Lameijer, H.; Thijssen, W.A.M.H.; Temorshuizen, F.; Boerma, C.; ... ; Groot, B. de 2022
Background Treatment and the clinical course during Emergency Department (ED) stay before Intensive Care Unit (ICU) admission may affect predicted mortality risk calculated by the Acute Physiology... Show moreBackground Treatment and the clinical course during Emergency Department (ED) stay before Intensive Care Unit (ICU) admission may affect predicted mortality risk calculated by the Acute Physiology and Chronic Health Evaluation (APACHE)-IV, causing lead-time bias. As a result, comparing standardized mortality ratios (SMRs) among hospitals may be difficult if they differ in the location where initial stabilization takes place. The aim of this study was to assess to what extent predicted mortality risk would be affected if the APACHE-IV score was recalculated with the initial physiological variables from the ED. Secondly, to evaluate whether ED Length of Stay (LOS) was associated with a change (delta) in these APACHE-IV scores. Methods An observational multicenter cohort study including ICU patients admitted from the ED. Data from two Dutch quality registries were linked: the Netherlands Emergency department Evaluation Database (NEED) and the National Intensive Care Evaluation (NICE) registry. The ICU APACHE-IV, predicted mortality, and SMR based on data of the first 24 h of ICU admission were compared with an ED APACHE-IV model, using the most deviating physiological variables from the ED or ICU. Results A total of 1398 patients were included. The predicted mortality from the ICU APACHE-IV (median 0.10; IQR 0.03-0.30) was significantly lower compared to the ED APACHE-IV model (median 0.13; 0.04-0.36; p < 0.01). The SMR changed from 0.63 (95%CI 0.54-0.72) to 0.55 (95%CI 0.47-0.63) based on ED APACHE-IV. Predicted mortality risk changed more than 5% in 321 (23.2%) patients by using the ED APACHE-IV. ED LOS > 3.9 h was associated with a slight increase in delta APACHE-IV of 1.6 (95% CI 0.4-2.8) compared to ED LOS < 1.7 h. Conclusion Predicted mortality risks and SMRs calculated by the APACHE IV scores are not directly comparable in patients admitted from the ED if hospitals differ in their policy to stabilize patients in the ED before ICU admission. Future research should focus on developing models to adjust for these differences. Show less
Nissen, S.K.; Candel, B.G.J.; Nickel, C.H.; Jonge, E. de; Ryg, J.; Bogh, S.B.; ... ; Brabrand, M. 2022
Study objective: To investigate how age affects the predictive performance of the National Early Warning Score (NEWS) at arrival to the emergency department (ED) regarding inhospital mortality and... Show moreStudy objective: To investigate how age affects the predictive performance of the National Early Warning Score (NEWS) at arrival to the emergency department (ED) regarding inhospital mortality and intensive care admission.Methods: International multicenter retrospective cohorts from 2 Danish and 3 Dutch ED. Development cohort: 14,809 Danish patients aged >= 18 years with at least systolic blood pressure or pulse measured from the Danish Multicenter Cohort. External validation cohort: 50,448 Dutch patients aged >18 years with all vital signs measured from the Netherlands Emergency Department Evaluation Database (NEED). Multivariable logistic regression was used for model building. Performance was evaluated overall and within age categories: 18 to 64 years, 65 to 80 years, and more than 80 years.Results: In the Danish Multicenter Cohort, a total of 2.5% died inhospital, and 2.8% were admitted to the ICU, compared with 2.8% and 1.6%, respectively, in the NEED. Age did not add information for the prediction of intensive care admission but was the strongest predictor for inhospital mortality. For NEWS alone, severe underestimation of risk was observed for persons above 80 while overall Area Under Receiver Operating Characteristic (AUROC) was 0.82 (confidence interval [CI] 0.80 to 0.84) in the Danish Multicenter Cohort versus 0.75 (CI 0.75 to 0.77) in the NEED. When combining NEWS with age, underestimation of risks was eliminated for persons above 80, and overall AUROC increased significantly to 0.86 (CI 0.85 to 0.88) in the Danish Multicenter Cohort versus 0.82 (CI 0.81 to 0.83) in the NEED.Conclusion: Combining NEWS with age improved the prediction performance regarding inhospital mortality, mostly for persons aged above 80, and can potentially improve decision policies at arrival to EDs. Show less
Candel, B.G.J.; Khoudja, J.; Gaakeer, M.I.; Avest, E. ter; Sir, O.; Lameijer, H.; ... ; Groot, B. de 2022
Appropriate interpretation of blood tests is important for risk stratification and guidelines used in the Emergency Department (ED) (such as SIRS or CURB-65). The impact of abnormal blood test... Show moreAppropriate interpretation of blood tests is important for risk stratification and guidelines used in the Emergency Department (ED) (such as SIRS or CURB-65). The impact of abnormal blood test values on mortality may change with increasing age due to (patho)-physiologic changes. The aim of this study was therefore to assess the effect of age on the case-mix adjusted association between biomarkers of renal function and homeostasis, inflammation and circulation and in-hospital mortality. This observational multi-center cohort study has used the Netherlands Emergency department Evaluation Database (NEED), including all consecutive ED patients >= 18 years of three hospitals. A generalized additive logistic regression model was used to visualize the association between in-hospital mortality, age and five blood tests (creatinine, sodium, leukocytes, C-reactive Protein, and hemoglobin). Multivariable logistic regression analyses were used to assess the association between the number of abnormal blood test values and mortality per age category (18-50; 51-65; 66-80; > 80 years). Of the 94,974 included patients, 2550 (2.7%) patients died in-hospital. Mortality increased gradually for C-reactive Protein (CRP), and had a U-shaped association for creatinine, sodium, leukocytes, and hemoglobin. Age significantly affected the associations of all studied blood tests except in leukocytes. In addition, with increasing age categories, case-mix adjusted mortality increased with the number of abnormal blood tests. In summary, the association between blood tests and (adjusted) mortality depends on age. Mortality increases gradually or in a U-shaped manner with increasing blood test values. Age-adjusted numerical scores may improve risk stratification. Our results have implications for interpretation of blood tests and their use in risk stratification tools and acute care guidelines. Show less
Candel, B.G.J.; Duijzer, R.; Gaakeer, M.I.; Avest, E. ter; Sir, O.; Lameijer, H.; ... ; Groot, B. de 2022
Background Appropriate interpretation of vital signs is essential for risk stratification in the emergency department (ED) but may change with advancing age. In several guidelines, risk scores such... Show moreBackground Appropriate interpretation of vital signs is essential for risk stratification in the emergency department (ED) but may change with advancing age. In several guidelines, risk scores such as the Systemic Inflammatory Response Syndrome (SIRS) and Quick Sequential Organ Failure Assessment (qSOFA) scores, commonly used in emergency medicine practice (as well as critical care) specify a single cut-off or threshold for each of the commonly measured vital signs. Although a single cut-off may be convenient, it is unknown whether a single cut-off for vital signs truly exists and if the association between vital signs and in-hospital mortality differs per age-category. Aims To assess the association between initial vital signs and case-mix adjusted in-hospital mortality in different age categories. Methods Observational multicentre cohort study using the Netherlands Emergency Department Evaluation Database (NEED) in which consecutive ED patients >= 18 years were included between 1 January 2017 and 12 January 2020. The association between vital signs and case-mix adjusted mortality were assessed in three age categories (18-65; 66-80; >80 years) using multivariable logistic regression. Vital signs were each divided into five to six categories, for example, systolic blood pressure (SBP) categories (<= 80, 81-100, 101-120, 121-140, >140 mm Hg). Results We included 101 416 patients of whom 2374 (2.3%) died. Adjusted ORs for mortality increased gradually with decreasing SBP and decreasing peripheral oxygen saturation (SpO(2)). Diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) had quasi-U-shaped associations with mortality. Mortality did not increase for temperatures anywhere in the range between 35.5 degrees C and 42.0 degrees C, with a single cut-off around 35.5 degrees C below which mortality increased. Single cut-offs were also found for MAP 22/min. For all vital signs, older patients had larger increases in absolute mortality compared with younger patients. Conclusion For SBP, DBP, SpO(2) and HR, no single cut-off existed. The impact of changing vital sign categories on prognosis was larger in older patients. Our results have implications for the interpretation of vital signs in existing risk stratification tools and acute care guidelines. Show less
Candel, B.G.J.; Dap, S.; Raven, W.; Lameijer, H.; Gaakeer, M.I.; Jonge, E. de; Groot, B. de 2022
Objective: The aim of this study was to investigate whether sex differences exist in disease presentations, disease severity and (case-mix adjusted) outcomes in the Emergency Department (ED)... Show moreObjective: The aim of this study was to investigate whether sex differences exist in disease presentations, disease severity and (case-mix adjusted) outcomes in the Emergency Department (ED).Methods: Observational multicenter cohort study using the Netherlands Emergency Department Evaluation Database (NEED), including patients >= 18 years of three Dutch EDs. Multivariable logistic regression was used to study the associations between sex and outcome measures in-hospital mortality and Intensive Care Unit/Medium Care Unit (ICU/MCU) admission in ED patients and in subgroups triage categories and presenting complaints.Results: Of 148,825 patients, 72,554 (48.8%) were females. Patient characteristics at ED presentation and diagnoses (such as pneumonia, cerebral infarction, and fractures) were comparable between sexes at ED presentation. In-hospital mortality was 2.2% in males and 1.7% in females. ICU/MCU admission was 4.7% in males and 3.1% in females. Males had higher unadjusted (OR 1.34(1.25-1.45)) and adjusted (AOR 1.34(1.24-1.46)) risks for mortality, and unadjusted (OR 1.54(1.46-1.63)) and adjusted (AOR 1.46(1.37-1.56)) risks for ICU/MCU admission. Males had higher adjusted mortality and ICU/MCU admission for all triage categories, and with almost all presenting complaints except for headache.Conclusions: Although patient characteristics at ED presentation for both sexes are comparable, males are at higher unadjusted and adjusted risk for adverse outcomes. Males have higher risks in all triage categories and with almost all presenting complaints. Future studies should investigate reasons for higher risk in male ED patients. Show less
Candel, B.G.J.; Ingen, I.B. van; Doormalen, I.P.H. van; Raven, W.; Mignot-Evers, L.A.A.; Jonge, E. de; Groot, B. de 2021
Purpose To assess how often baseline systolic blood pressure (SBP) could be retrieved from the Electronic Health Record (EHR) in older Emergency Department (ED) patients. Second, to assess whether... Show morePurpose To assess how often baseline systolic blood pressure (SBP) could be retrieved from the Electronic Health Record (EHR) in older Emergency Department (ED) patients. Second, to assess whether the difference between baseline SBP and initial SBP in the ED (Delta SBP) was associated with 30-day mortality. Methods A multicenter hypothesis-generating cohort study including patients >= 70 years. EHRs were searched for baseline SBPs. The association between Delta SBP and 30-day mortality was investigated. Results Baseline SBP was found in 220 out of 300 patients (73.3%; 95%CI 68.1-78.0%). In 72 patients with normal initial SBPs (133-166 mmHg) in the ED, fifteen (20.8%) had a negative Delta SBP with 20.0% mortality. A negative Delta SBP was associated with 30-day mortality (AHR 4.7; 1.7-12.7). Conclusion Baseline SBPs are often available in older ED patients. The Delta SBP has prognostic value and could be used as an extra variable to recognize hypotension in older ED patients. Future studies should clarify whether the Delta SBP improves risk stratification in the ED.Key summary pointsAim To investigate whether a baseline systolic blood pressure (SBP) in older Emergency Department (ED) patients of >= 70 years has prognostic value, when compared with the initial SBP at presentation in the ED (= Delta SBP). Findings A baseline SBP could be retrieved from the Electronic Health Record for most older ED patients (73.3%). A negative Delta SBP was associated with 30-day mortality. In 20% of the patients with a normal initial SBP in the ED, the Delta SBP was negative, with a high mortality rate. Message A baseline SBP value could be retrieved from the Electronic Health Record in most hospitalized ED patients >= 70 years. In addition, the 21% with a normal SBP at ED presentation had a negative Delta SBP and these patients had an increased risk for 30-day mortality. As a result, Delta SBP may contribute to improved risk stratification and may help to recognize hypotension in older patients. Show less
