Rationale: Supplemental oxygen is widely administered to ICU patients, but appropriate oxygenation targets remain unclear.Objectives: This study aimed to determine whether a low-oxygenation... Show moreRationale: Supplemental oxygen is widely administered to ICU patients, but appropriate oxygenation targets remain unclear.Objectives: This study aimed to determine whether a low-oxygenation strategy would lower 28-day mortality compared with a high-oxygenation strategy.Methods: This randomized multicenter trial included mechanically ventilated ICU patients with an expected ventilation duration of at least 24 hours. Patients were randomized 1:1 to a low-oxygenation (Pa-O2, 55-80mmHg; or oxygen saturation as measured by pulse oximetry, 91-94%) or high-oxygenation (Pa-O2, 110-150mmHg; or oxygen saturation as measured by pulse oximetry, 96-100%) target until ICU discharge or 28 days after randomization, whichever came first. The primary outcome was 28-day mortality. The study was stopped prematurely because of the COVID-19 pandemic when 664 of the planned 1,512 patients were included.Measurements and Main Results: Between November 2018 and November 2021, a total of 664 patients were included in the trial: 335 in the low-oxygenation group and 329 in the high-oxygenation group. The median achieved Pa-O2 was 75mmHg (interquartile range, 70-84) and 115mmHg (interquartile range, 100-129) in the low- and high-oxygenation groups, respectively. At Day 28, 129 (38.5%) and 114 (34.7%) patients had died in the low- and high-oxygenation groups, respectively (risk ratio, 1.11; 95% confidence interval, 0.9-1.4; P = 0.30). At least one serious adverse event was reported in 12 (3.6%) and 17 (5.2%) patients in the low- and high-oxygenation groups, respectively.Conclusions: Among mechanically ventilated ICU patients with an expected mechanical ventilation duration of at least 24 hours, using a low-oxygenation strategy did not result in a reduction of 28-day mortality compared with a high-oxygenation strategy. 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
Bos, M.K.; Lam, S.W.; Motta, G.; Helmijr, J.C.A.; Beaufort, C.M.; Jonge, E. de; ... ; Sleijfer, S. 2023
BackgroundESR1 mutations have been identified as mechanism for endocrine resistance and are also associated with a decreased overall survival. We assessed ESR1 mutations in circulating tumor DNA ... Show moreBackgroundESR1 mutations have been identified as mechanism for endocrine resistance and are also associated with a decreased overall survival. We assessed ESR1 mutations in circulating tumor DNA (ctDNA) for impact on outcome to taxane-based chemotherapy in advanced breast cancer patients.MethodsESR1 mutations were determined in archived plasma samples from patients treated with paclitaxel and bevacizumab (AT arm, N = 91) in the randomized phase II ATX study. Samples collected at baseline (n = 51) and at cycle 2 (n = 13, C2) were analyzed using a breast cancer next-generation sequencing panel. This study was powered to detect a benefit in progression-free survival (PFS) at six months for patients treated with paclitaxel/bevacizumab compared to historical trials with fulvestrant. PFS, overall survival (OS), and ctDNA dynamics were exploratory analyses.ResultsPFS at six months was 86% (18/21) in patients with an ESR1 mutation detected and 85% (23/27) in wildtype ESR1 patients. In our exploratory analysis, median progression-free survival (PFS) was 8.2 months [95% CI, 7.6-8.8] for ESR1 mutant patients versus 8.7 months [95% confidence interval (CI), 8.3-9.2] for ESR1 wildtype patients [p = 0.47]. The median overall survival (OS) was 20.7 months [95% CI, 6.6-33.7] for ESR1 mutant patients versus 28.1 months [95% confidence interval (CI), 19.3-36.9] for ESR1 wildtype patients [p = 0.27]. Patients with >= two ESR1 mutations had a significantly worse OS, but not PFS, compared to those who did not [p = 0.003]. Change in ctDNA level at C2 was not different between ESR1 and other mutations.ConclusionsPresence of ESR1 mutations in baseline ctDNA might not be associated with inferior PFS and OS in advanced breast cancer patients treated with paclitaxel/bevacizumab. Show less
Paassen, J. van; Graaf-Dijkstra, A. de; Brunsveld-Reinders, A.H.; Jonge, E. de; Klautz, R.J.M.; Tsonaka, R.; ... ; Arbous, M.S. 2023
OBJECTIONS: Development of acute lung injury after cardiac surgery is associated with an unfavourable outcome. Acute respiratory distress syndrome in general is, besides cytokine and interleukin... Show moreOBJECTIONS: Development of acute lung injury after cardiac surgery is associated with an unfavourable outcome. Acute respiratory distress syndrome in general is, besides cytokine and interleukin activation, associated with activation of platelets, monocytes and neutrophils. In relation to pulmonary outcome after cardiac surgery, leucocyte and platelet activation is described in animal studies only. Therefore, we explored the perioperative time course of platelet and leucocyte activation in cardiac surgery and related these findings to acute lung injury assessed via PaO2/FiO(2) (P/F) ratio measurements. METHODS: A prospective cohort study was performed, including 80 cardiac surgery patients. At five time points, blood samples were directly assessed by flow cytometry. For time course analyses in low (< 200) versus high (>200) P/F ratio groups, repeated measurement techniques with linear mixed models were used. RESULTS: Already before the start of the operation, platelet activatability (P = 0.003 for thrombin receptor-activator peptide and P = 0.017 for adenosine diphosphate) was higher, and the expression of neutrophil activation markers was lower (CD18/CD11; P = 0.001, CD62L; P = 0.013) in the low P/F group. After correction for these baseline differences, the peri- and postoperative thrombin receptor-activator peptide-induced thrombocyte activatability was decreased in the low P/F ratio group (P = 0.008), and a changed pattern of neutrophil activation markers was observed. CONCLUSIONS: Prior to surgery, an upregulated inflammatory state with higher platelet activatability and indications for higher neutrophil turnover were demonstrated in cardiac surgery patients who developed lung injury. It is difficult to distinguish whether these factors are mediators or are also aetiologically related to the development of lung injury after cardiac surgery. Further research is warranted. Show less
Background Central nervous system (CNS) metastases are present in approximately 40% of patients with metastatic epidermal growth factor receptor-mutated (EGFRm+) non-small cell lung cancer (NSCLC).... Show moreBackground Central nervous system (CNS) metastases are present in approximately 40% of patients with metastatic epidermal growth factor receptor-mutated (EGFRm+) non-small cell lung cancer (NSCLC). The EGFR-tyrosine kinase inhibitor osimertinib is a substrate of transporters ABCB1 and ABCG2 and metabolized by CYP3A4. We investigated relationships between single nucleotide polymorphisms (SNPs) ABCB1 3435C>T, ABCG2 421C>A and 34G>A, and CYP3A4*22 and CNS treatment efficacy of osimertinib in EGFRm+ NSCLC patients. Methods Patients who started treatment with osimertinib for EGFRm+ NSCLC between November 2014 and June 2021 were included in this retrospective observational multicentre cohort study. For patients with baseline CNS metastases, the primary endpoint was CNS progression-free survival (CNS-PFS; time from osimertinib start until CNS disease progression or death). For patients with no or unknown baseline CNS metastases, the primary endpoint was CNS disease-free survival (CNS-DFS; time from osimertinib start until occurrence of new CNS metastases). Relationships between SNPs and baseline characteristics with CNS-PFS and CNS-DFS were studied with competing-risks survival analysis. Secondary endpoints were relationships between SNPs and PFS, overall survival, severe toxicity, and osimertinib pharmacokinetics. Findings From 572 included patients, 201 had baseline CNS metastases. No SNP was associated with CNS-PFS. Genotype ABCG2 34GA/AA and/or ABCB1 3435CC -present in 35% of patients- was significantly associated with decreased CNS-DFS (hazard ratio 0.28; 95% CI 0.11-0.73; p = 0.009) in the multivariate analysis. This remained significant after applying a Bonferroni correction and internal validation through bootstrapping. ABCG2 421CA/ AA was related to more severe toxicity (27.0% versus 16.5%; p = 0.010). Interpretation ABCG2 34G>A and ABCB1 3435C>T are predictors for developing new CNS metastases during osi-mertinib treatment, probably because of diminished drug levels in the CNS. ABCG2 421C>A was significantly related with the incidence of severe toxicity. Pre-emptive genotyping for these SNPs could individualize osimertinib therapy. Addition of ABCG2 inhibitors for patients without ABCG2 34G>A should be studied further, to prevent new CNS metastases during osimertinib treatment. Show less
Jonge, E. de; Vooren, M. van der; Gillis, J.M.E.P.; Prado, M.R. del; Wigbers, J.; Bakhshi-Raiez, F.; Kraemer, C.V.E. 2022
Background: Supplementation of calcium during continuous venovenous hemofiltration (CVVH) with citrate anticoagulation is usually titrated using a target blood ionized calcium concentration. Plasma... Show moreBackground: Supplementation of calcium during continuous venovenous hemofiltration (CVVH) with citrate anticoagulation is usually titrated using a target blood ionized calcium concentration. Plasma calcium concentrations may be normal despite substantial calcium loss, by mobilization of calcium from the skeleton. Aim of our study is to develop an equation to calculate CVVH calcium and to retrospectively calculate CVVH calcium balance in a cohort of ICU-patients. Methods: This is a single-center retrospective observational cohort study. In a subcohort of patients, all calcium excretion measurements in patients treated with citrate CVVH were randomly divided into a development set (n = 324 in 42 patients) and a validation set (n = 441 in 42 different patients). Using mixed linear models, we developed an equation to calculate calcium excretion from routinely available parameters. We retrospectively calculated calcium balance in 788 patients treated with citrate CVVH between 2014 and 2021. Results: Calcium excretion (mmol/24 h) was - 1.2877 + 0.646*[Ca](blood,total) * ultrafiltrate (l/24 h) + 0.107*blood flow (ml/h). The mean error of the estimation was - 1.0 +/- 6.7 mmol/24 h, the mean absolute error was 4.8 +/- 4.8 mmol/24 h. Calculated calcium excretion was 105.8 +/- 19.3 mmol/24 h. Mean daily CVVH calcium balance was - 12.0 +/- 20.0 mmol/24 h. Mean cumulative calcium balance ranged from - 3687 to 448 mmol. Conclusion: During citrate CVVH, calcium balance was negative in most patients, despite supplementation of calcium based on plasma ionized calcium levels. This may contribute to demineralization of the skeleton. We propose that calcium supplementation should be based on both plasma ionized calcium and a simple calculation of calcium excretion by CVVH.[GRAPHICS]. 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
Background: Oxygen therapy is a widely used intervention in acutely ill patients in the intensive care unit (ICU). It is established that not only hypoxia, but also prolonged hyperoxia is... Show moreBackground: Oxygen therapy is a widely used intervention in acutely ill patients in the intensive care unit (ICU). It is established that not only hypoxia, but also prolonged hyperoxia is associated with poor patient-centered outcomes. Nevertheless, a fundamental knowledge gap remains regarding optimal oxygenation for critically ill patients. In this randomized clinical trial, we aim to compare ventilation that uses conservative oxygenation targets with ventilation that uses conventional oxygen targets with respect to mortality in ICU patients.Methods: The "ConservatIve versus CONventional oxygenation targets in Intensive Care patients" trial (ICONIC) is an investigator-initiated, international, multicenter, randomized clinical two-arm trial in ventilated adult ICU patients. The ICONIC trial will run in multiple ICUs in The Netherlands and Italy to enroll 1512 ventilated patients. ICU patients with an expected mechanical ventilation time of more than 24 h are randomized to a ventilation strategy that uses conservative (PaO2 55-80 mmHg (7.3-10.7 kPa)) or conventional (PaO2 110-150 mmHg (14.7-20 kPa)) oxygenation targets. The primary endpoint is 28-day mortality. Secondary endpoints are ventilator-free days at day 28, ICU mortality, in-hospital mortality, 90-day mortality, ICU- and hospital length of stay, ischemic events, quality of life, and patient opinion of research and consent in the emergency setting.Discussion: The ICONIC trial is expected to provide evidence on the effects of conservative versus conventional oxygenation targets in the ICU population. This study may guide targeted oxygen therapy in the future. Show less
Raven, W.; Hoven, E.M.P. van den; Gaakeer, M.I.; Avest, E. ter; Sir, O.; Lameijer, H.; ... ; Groot, B. de 2022
Background and importance Although aging societies in Western Europe use presenting complaints (PCs) in emergency departments (EDs) triage systems to determine the urgency and severity of the care... Show moreBackground and importance Although aging societies in Western Europe use presenting complaints (PCs) in emergency departments (EDs) triage systems to determine the urgency and severity of the care demand, it is unclear whether their prognostic value is age-dependent.Objective To assess the frequency and association of PCs with hospitalization and mortality across age categories.Methods An observational multicenter study using all consecutive visits of three EDs in the Netherlands Emergency department Evaluation Database. Patients were stratified by age category (0-18; 19-50; 51-65; 66-80; >80 years), in which the association between PCs and case-mix adjusted hospitalization and mortality was studied using multivariable logistic regression analysis (adjusting for demographics, hospital, disease severity, comorbidity and other PCs)Results We included 172 104 ED-visits. The most frequent PCs were 'extremity problems' [range across age categories (13.5-40.8%)], 'feeling unwell' (9.5-23.4%), 'abdominal pain' (6.0-13.9%), 'dyspnea' (4.5-13.3%) and 'chest pain' (0.6-10.7%). For most PCs, the observed and the case-mix-adjusted odds for hospitalization and mortality increased the higher the age category. The most common PCs with the highest adjusted odds ratios (AORs, 95% CI) for hospitalization were 'diarrhea and vomiting' [2.30 (2.02-2.62)] and 'feeling unwell' [1.60 (1.48-1.73)]. Low hospitalization risk was found for 'chest pain' [0.58 (0.53-0.63)] and `palpitations' [0.64 (0.58-0.71)].Conclusions Frequency of PCs in ED patients varies with age, but the same PCs occur in all age categories. For most PCs, (case-mix adjusted) hospitalization and mortality vary across age categories. 'Chest pain' and 'palpitations,' usually triaged 'very urgent', carry a low risk for hospitalization and mortality. European Journal of Emergency Medicine 29: 33-41 Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved. 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
Grim, C.C.A.; Termorshuizen, F.; Bosman, R.J.; Cremer, O.L.; Meinders, A.J.; Nijsten, M.W.N.; ... ; Jonge, E. de 2021
OBJECTIVES: In critically ill patients, dysnatremia is common, and in these patients, in-hospital mortality is higher. It remains unknown whether changes of serum sodium after ICU admission affect... Show moreOBJECTIVES: In critically ill patients, dysnatremia is common, and in these patients, in-hospital mortality is higher. It remains unknown whether changes of serum sodium after ICU admission affect mortality, especially whether normalization of mild hyponatremia improves survival. DESIGN: Retrospective cohort study. SETTING: Ten Dutch ICUs between January 2011 and April 2017. Patients: Adult patients were included if at least one serum sodium measurement within 24 hours of ICU admission and at least one serum sodium measurement 24-48 hours after ICU admission were available. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A logistic regression model adjusted for age, sex, and Acute Physiology and Chronic Health Evaluation-IV-predicted mortality was used to assess the difference between mean of sodium measurements 24-48 hours after ICU admission and first serum sodium measurement at ICU admission (Delta 48 hr-[Na]) and in-hospital mortality. In total, 36,660 patients were included for analysis. An increase in serum sodium was independently associated with a higher risk of in-hospital mortality in patients admitted with normonatremia (Delta 48 hr-[Na] 5-10 mmol/L odds ratio: 1.61 [1.44-1.79], Delta 48 hr-[Na] > 10 mmol/L odds ratio: 4.10 [3.20-5.24]) and hypernatremia (Delta 48 hr-[Na] 5-10 mmol/L odds ratio: 1.47 [1.02-2.14], Delta 48 hr-[Na] > 10 mmol/L odds ratio: 8.46 [3.31-21.64]). In patients admitted with mild hyponatremia and Delta 48 hr-[Na] greater than 5 mmol/L, no significant difference in hospital mortality was found (odds ratio, 1.11 [0.99-1.25]). CONCLUSIONS: An increase in serum sodium in the first 48 hours of ICU admission was associated with higher in-hospital mortality in patients admitted with normonatremia and in patients admitted with hypernatremia. 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
Objective: Early identification of emergency department (ED) patients who need hospitalization is essential for quality of care and patient safety. We aimed to compare machine learning (ML) models... Show moreObjective: Early identification of emergency department (ED) patients who need hospitalization is essential for quality of care and patient safety. We aimed to compare machine learning (ML) models predicting the hospitalization of ED patients and conventional regression techniques at three points in time after ED registration.Methods: We analyzed consecutive ED patients of three hospitals using the Netherlands Emergency Department Evaluation Database (NEED). We developed prediction models for hospitalization using an increasing number of data available at triage, similar to 30 min (including vital signs) and similar to 2 h (including laboratory tests) after ED registration, using ML (random forest, gradient boosted decision trees, deep neural networks) and multivariable logistic regression analysis (including spline transformations for continuous predictors). Demographics, urgency, presenting complaints, disease severity and proxies for comorbidity, and complexity were used as covariates. We compared the performance using the area under the ROC curve in independent validation sets from each hospital.Results: We included 172,104 ED patients of whom 66,782 (39 %) were hospitalized. The AUC of the multi-variable logistic regression model was 0.82 (0.78-0.86) at triage, 0.84 (0.81-0.86) at similar to 30 min and 0.83 (0.75-0.92) after similar to 2 h. The best performing ML model over time was the gradient boosted decision trees model with an AUC of 0.84 (0.77-0.88) at triage, 0.86 (0.82-0.89) at similar to 30 min and 0.86 (0.74-0.93) after similar to 2 h.Conclusions: Our study showed that machine learning models had an excellent but similar predictive performance as the logistic regression model for predicting hospital admission. In comparison to the 30-min model, the 2-h model did not show a performance improvement. After further validation, these prediction models could support management decisions by real-time feedback to medical personal. Show less
Background: Whereas accumulating studies on patients with coronavirus disease 2019 (COVID-19) report high incidences of thrombotic complications, large studies on clinically relevant thrombosis in... Show moreBackground: Whereas accumulating studies on patients with coronavirus disease 2019 (COVID-19) report high incidences of thrombotic complications, large studies on clinically relevant thrombosis in patients with other respiratory tract infections are lacking. How this high risk in COVID-19 patients compares to those observed in hospitalized patients with other viral pneumonias such as influenza is unknown.Objectives: To assess the incidence of venous and arterial thrombotic complications in hospitalized patients with influenza as opposed to that observed in hospitalized patients with COVID-19.Methods: This was a retrospective cohort study; we used data from Statistics Netherlands (study period: 2018) on thrombotic complications in hospitalized patients with influenza. In parallel, we assessed the cumulative incidence of thrombotic complications-adjusted for competing risk of death-in patients with COVID-19 in three Dutch hospitals (February 24 to April 26, 2020).Results: Of the 13 217 hospitalized patients with influenza, 437 (3.3%) were diagnosed with thrombotic complications, versus 66 (11%) of the 579 hospitalized patients with COVID-19. The 30-day cumulative incidence of any thrombotic complication in influenza was 11% (95% confidence interval [CI], 9.4-12) versus 25% (95% CI, 18-32) in COVID-19. For venous thrombotic (VTC) complications and arterial thrombotic complications alone, these numbers were, respectively, 3.6% (95% CI, 2.7-4.6) and 7.5% (95% CI, 6.3-8.8) in influenza versus 23% (95% CI, 16-29) and 4.4% (95% CI, 1.9-8.8) in COVID-19.Conclusions: The incidence of thrombotic complications in hospitalized patients with influenza was lower than in hospitalized patients with COVID-19. This difference was mainly driven by a high risk of VTC complications in the patients with COVID-19 admitted to the Intensive Care Unit. Remarkably, patients with influenza were more often diagnosed with arterial thrombotic complications. Show less
