Predictive performance of comorbidity for 30-day and 1-year mortality in patients with bloodstream infection visiting the emergency department: a retrospective cohort study.

OBJECTIVES: To investigate whether the Charlson Comorbidity Index (CCI) predicted short-term and long-term mortality in patients with a bloodstream infection visiting the emergency department (ED) and compare it to the often-validated National Early Warning Score (NEWS). DESIGN: A retrospective cohort study. SETTING: A tertiary hospital in the Netherlands. PARTICIPANTS: Adult patients attending the ED with a blood culture-proven infection between 2012 and 2017 were included. We collected the comorbidities from the CCI and the vital signs from the NEWS. MAIN OUTCOMES: Short-term mortality (30-day) and long-term mortality (1 year). We assessed the predictive performance by discrimination, expressed as the area under the curve (AUC). RESULTS: We included 1039 patients with a blood culture-proven infection. Mortality was 10.4% within 30 days and 27.8% within 1 year. On average patients had two comorbidities (ranging from 0 to 6). Highly prevalent comorbidities were malignancy (30.2%) and diabetes mellitus (20.5%). The predictive performance of the CCI was highest for 1-year mortality (AUC 0.696 (95%CI) (0.660 to 0.732)) and better compared with the NEWS (AUC (95% CI) 0.594 (0.555 to 0.632)). For prediction of 30-day mortality, the NEWS was superior (AUC (95% CI) 0.706 (0.656 to 0.756)) to the comorbidities of the CCI (AUC (95% CI) 0.568 (0.507 to 0.628)). CONCLUSIONS: We found that presenting comorbidity (ie, the CCI) is most useful to prognosticate long-term outcome in patients with bloodstream infection in the ED. Short-term mortality is more accurately predicted by deviating vital signs (ie, the NEWS).

Predicting inhospital admission at the emergency department: a systematic review.

BACKGROUND: ED crowding has potential detrimental consequences for both patient care and staff. Advancing disposition can reduce crowding. This may be achieved by using prediction models for admission. This systematic review aims to present an overview of prediction models for admission at the ED. Furthermore, we aimed to identify the best prediction tool based on its performance, validation, calibration and clinical usability. METHODS: We included observational studies published in Embase.com, Medline Ovid, Cochrane CENTRAL, Web of Science Core Collection or Google scholar, in which admission models were developed or validated in a general medical population in European EDs including the UK. We used the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist to assess quality of model development. Model performance was presented as discrimination and calibration. The search was performed on 11 October 2020. RESULTS: In total, 18 539 articles were identified. We included 11 studies, describing 16 different models, comprising the development of 9 models and 12 external validations of 11 models. The risk of bias of the development studies was considered low to medium. Discrimination, as represented by the area under the curve ranged from 0.630 to 0.878. Calibration was assessed in seven models and was strong. The best performing models are the models of Lucke et al and Cameron et al. These models combine clinical applicability, by inclusion of readily available parameters, and appropriate discrimination, calibration and validation. CONCLUSION: None of the models are yet implemented in EDs. Further research is needed to assess the applicability and implementation of the best performing models in the ED. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42017057975.

The association of body temperature with antibiotic therapy and mortality in patients attending the emergency department with suspected infection.

BACKGROUND AND IMPORTANCE: Previous studies found that septic patients with normothermia have higher mortality than patients with fever. We hypothesize that antibiotic therapy is less frequently initiated if infectious patients present with normothermia to the emergency department (ED). OBJECTIVES: To examine the association of body temperature with the initiation of antibiotic therapy in patients attending the ED with suspected and proven infection. Additionally, the association of temperature with 30-day mortality was assessed. DESIGN, SETTINGS AND PARTICIPANTS: We conducted a retrospective cohort study between 2012 and 2016 at a tertiary university hospital. Adult patients attending the ED with a blood culture taken (i.e. suspected infection) and a positive blood culture (i.e. proven bacteremia) were included. EXPOSURE: Tympanic temperature at arrival was categorized as hypothermia (<36.1°C), normothermia (36.1-38.0°C) or hyperthermia (>38.0°C). OUTCOME MEASURES AND ANALYSIS: Primary outcome was the initiation of antibiotic therapy. A secondary outcome was 30-day mortality. Multivariable logistic regression was used to control for covariates. MAIN RESULTS: Of 5997 patients with a suspected infection, 45.8% had normothermia, 44.6% hyperthermia and 5.6% hypothermia. Patients with hyperthermia received more often antibiotic therapy (53.5%) compared to normothermic patients (27.6%, adjusted odds ratio [95% confidence interval], 2.59 [2.27-2.95]). Patients with hyperthermia had lower mortality (4.7%) than those with normothermia (7.4%, adjusted odds ratio [95% confidence interval], 0.50 [0.39-0.64]). Sensitivity analyses in patients with proven bacteremia (n = 934) showed similar results. CONCLUSION: Normothermia in patients presenting with infection was associated with receiving less antibiotic therapy in the ED compared to presentations with hyperthermia. Moreover, normothermia was associated with a higher mortality risk than hyperthermia.

Predicting 30-day mortality using point-of-care testing; an external validation and derivation study.

BACKGROUND: Early risk stratification for guiding treatment priority in the emergency department (ED) is becoming increasingly important. Existing prediction models typically use demographics, vital signs and laboratory parameters. Laboratory-based models require blood testing, which may cause substantial delay. However, these delays can be prevented by the use of point-of-care testing (POCT), where results are readily available. We aimed to externally validate a laboratory-based model for mortality and subsequently assessed whether a POCT model yields comparable performance. METHODS: All adult patients visiting the ED of a university hospital between January 1st, 2012 and December 31st, 2016 were retrospectively reviewed for inclusion. Primary outcome was defined as 30-day mortality after ED presentation. We externally validated one existing prediction model including age, glucose, urea, sodium, haemoglobin, platelet count and white blood cell count. We assessed the predictive performance by discrimination, expressed as Area under the Curve (AUC). We compared the existing model to an equivalent model using predictors that are available with POCT (i.e. glucose, urea, sodium and haemoglobin). Additionally, we internally validated these models with bootstrapping. RESULTS: We included 34,437 patients of whom 1,942 (5.6%) died within 30 days. The AUC of the laboratory-based model was 0.794. We refitted this model to our ED population and found an AUC of 0.812, which decreased only slightly to 0.790 with only POCT parameters. CONCLUSIONS: Our POCT-model performs similar to existing laboratory-based models in identifying patients at high risk for mortality, with results available within minutes. Although the model needs further validation and evaluation, it shows the potential of POCT for early risk stratification in the ED.

Non-adherence to antimicrobial guidelines in patients with bloodstream infection visiting the emergency department.

OBJECTIVE: Non-adherence to antimicrobial guidelines in patients with bloodstream infection can result in undertreatment, overtreatment, or equivalent treatment, and could lead to suboptimal care. Our aim was to examine the association between non-adherence and appropriate coverage as well as to assess the impact of non-adherence on 30-day mortality. METHODS: We conducted a retrospective cohort study between 2012 and 2017 at a tertiary university hospital. Adult patients attending the emergency department with a bloodstream infection were included. Adherence was defined as guideline-recommended antibiotic therapy. Non-adherence was either undertreatment (too narrow-spectrum), overtreatment (too broad-spectrum), or equivalent treatment. Outcomes were appropriate coverage (i.e. antibiotic therapy that matches in vitro susceptibility of the isolated bacteria) and 30-day mortality. RESULTS: We included 909 patients of whom 395 (43.5%) were treated adherently, 355 (39.1%) were undertreated, 87 (9.6%) were overtreated, and 72 (7.9%) received an equivalent treatment. Overtreated patients were more severely ill, whilst undertreated patients had more favorable patient characteristics. Overtreatment did not result in higher appropriate coverage, whereas undertreatment was associated with lower coverage (OR[95%CI]: 0.18 [0.12; 0.26]). Overtreatment and undertreatment were not associated with 30-day mortality. CONCLUSIONS: Guideline adherence likely depends on disease severity, because overtreatment was more often observed in patients with high disease severity and undertreatment in less severely ill patients. Undertreatment was associated lower appropriate coverage but not with higher mortality. However, this can be the result of residual confounding . Overtreatment did not result in higher appropriate antibiotic coverage nor a survival benefit . Therefore, overtreatment seems not justifiable.

Appropriate empirical antibiotic therapy and mortality: Conflicting data explained by residual confounding.

OBJECTIVE: Clinical practice universally assumes that appropriate empirical antibiotic therapy improves survival in patients with bloodstream infection. However, this is not generally supported by previous studies. We examined the association between appropriate therapy and 30-day mortality, while minimizing bias due to confounding by indication. METHODS: We conducted a retrospective cohort study between 2012 and 2017 at a tertiary university hospital in the Netherlands. Adult patients with bloodstream infection attending the emergency department were included. Based on in vitro susceptibility, antibiotic therapy was scored as appropriate or inappropriate. Primary outcome was 30-day mortality. To control for confounding, we performed conventional multivariable logistic regression and propensity score methods. Additionally, we performed an analysis in a more homogeneous subgroup (i.e. antibiotic monotherapy). RESULTS: We included 1.039 patients, 729 (70.2%) received appropriate therapy. Overall 30-day mortality was 10.4%. Appropriately treated patients had more unfavorable characteristics, indicating more severe illness. Despite adjustments, we found no association between appropriate therapy and mortality. For the antibiotic monotherapy subgroup (n = 449), patient characteristics were more homogeneous. Within this subgroup, appropriate therapy was associated with lower mortality (Odds Ratios [95% Confidence Intervals] ranging from: 0.31 [0.14; 0.67] to 0.40 [0.19; 0.85]). CONCLUSIONS: Comparing heterogeneous treatment groups distorts associations despite use of common methods to prevent bias. Consequently, conclusions of such observational studies should be interpreted with care. If possible, future investigators should use our method of attempting to identify and analyze the most homogeneous treatment groups nested within their study objective, because this minimizes residual confounding.

Vital signs and impaired cognition in older emergency department patients: The APOP study.

BACKGROUND/OBJECTIVES: Cognitive impairment is a frequent problem among older patients attending the Emergency Department (ED) and can be the result of pre-existing cognitive impairment, delirium, or neurologic disorders. Another cause can also be acute disturbance of brain perfusion and oxygenation, which may be reversed by optimal resuscitation. This study aimed to assess the relationship between vital signs, as a measure of acute hemodynamic changes, and cognitive impairment in older ED patients. DESIGN: Prospective cohort study. SETTING: ED's of two tertiary care and two secondary care hospitals in the Netherlands. PARTICIPANTS: 2629 patients aged 70-years and older. MEASUREMENTS: Vital signs were measured at the moment of ED arrival as part of routine clinical care. Cognition was measured using the Six-Item Cognitive Impairment Test (6-CIT). RESULTS: The median age of patients was 78 years (IQR 74-84). Cognitive impairment was present in 738 patients (28.1%). When comparing lowest with highest quartiles, a systolic blood pressure of <129 mmHg (OR 1.30, 95% confidence interval (95%CI) 0.98-1.73)was associated with increased risk of cognitive impairment. A higher respiratory rate (>21/min) was associated with increased risk of impaired cognition (OR 2.16, 95% CI 1.58-2.95) as well as oxygen saturation of <95% (OR 1.64, 95%CI 1.24-2.19). CONCLUSION: Abnormal vital signs associated with decreased brain perfusion and oxygenation are also associated with cognitive impairment in older ED patients. This may partially be explained by the association between disease severity and delirium, but also by acute disturbance of brain perfusion and oxygenation. Future studies should establish whether normalization of vital signs will also acutely improve cognition.

Predicting mortality in patients with suspected sepsis at the Emergency Department; A retrospective cohort study comparing qSOFA, SIRS and National Early Warning Score.

OBJECTIVE: In hospitalized patients, the risk of sepsis-related mortality can be assessed using the quick Sepsis-related Organ Failure Assessment (qSOFA). Currently, different tools that predict deterioration such as the National Early Warning Score (NEWS) have been introduced in clinical practice in Emergency Departments (ED) worldwide. It remains ambiguous which screening tool for mortality at the ED is best. The objective of this study was to evaluate the predictive performance for mortality of two sepsis-based scores (i.e. qSOFA and Systemic Inflammatory Response Syndrome (SIRS)-criteria) compared to the more general NEWS score, in patients with suspected infection directly at presentation to the ED. METHODS: We performed a retrospective cohort study. Patients who presented to the ED between June 2012 and May 2016 with suspected sepsis in a large tertiary care center were included. Suspected sepsis was defined as initiation of intravenous antibiotics and/or collection of any culture in the ED. Outcome was defined as 10-day and 30-day mortality after ED presentation. Predictive performance was expressed as discrimination (AUC) and calibration using Hosmer-Lemeshow goodness-of-fit test. Subsequently, sensitivity, and specificity were calculated. RESULTS: In total 8,204 patients were included of whom 286 (3.5%) died within ten days and 490 (6.0%) within 30 days after presentation. NEWS had the best performance, followed by qSOFA and SIRS (10-day AUC: 0.837, 0.744, 0.646, 30-day AUC: 0.779, 0.697, 0.631). qSOFA (≥2) lacked a high sensitivity versus SIRS (≥2) and NEWS (≥7) (28.5%, 77.2%, 68.0%), whilst entailing highest specificity versus NEWS and SIRS (93.7%, 66.5%, 37.6%). CONCLUSIONS: NEWS is more accurate in predicting 10- and 30-day mortality than qSOFA and SIRS in patients presenting to the ED with suspected sepsis.

Drug nonadherence is a common but often overlooked cause of hypertensive urgency and emergency at the emergency department.

OBJECTIVES: Over 70% of patients who visit the emergency department with a hypertensive emergency or a hypertensive urgency have previously been diagnosed with hypertension. Drug nonadherence is assumed to play an important role in development of hypertensive urgency and hypertensive emergency, but exact numbers are lacking. We aimed to retrospectively compare characteristics of patients with hypertensive urgency and hypertensive emergency and to prospectively quantify the attribution of drug nonadherence. METHODS: We retrospectively analysed clinical data including information on nonadherence obtained by treating physicians of patients with SBP at least 180 mmHg and DBP at least 110 mmHg visiting the emergency department between 2012 and 2015. We prospectively studied drug adherence among patients admitted to the emergency department with severely elevated BP by measuring plasma drug levels using liquid chromatography tandem mass spectrometry from September 2016 to March 2017. RESULTS: Of the 1163 patients retrospectively analysed, 257 (22.0%) met the criteria for hypertensive urgency and 356 (30.6%) for hypertensive emergency. Mean SBP (SD) was 203 (19) mmHg and mean DBP 121 (12) mmHg. Mean age was 60.1 (14.6) years; 55.1% were men. In 6.3% of patients with hypertensive urgency or hypertensive emergency, nonadherence was recorded as an attributing factor. Of the 59 patients prospectively analysed, 18 (30.5%) were nonadherent for at least one of the prescribed antihypertensive drugs. CONCLUSION: Hypertensive urgency and hypertensive emergency are common health problems resulting in frequent emergency department admissions. Workup of patients with a hypertensive urgency or hypertensive emergency should include an assessment of drug adherence to optimize treatment strategy.

CAM-ICU may not be the optimal screening tool for early delirium screening in older emergency department patients: a prospective cohort study.

OBJECTIVES: Delirium is a frequent problem among older patients in the emergency department (ED) and early detection is important to prevent its associated adverse outcomes. Several screening tools for delirium have been proposed for the ED, such as the 6-Item Cognitive Impairment Test (6-CIT) and the Confusion Assessment Method-ICU (CAM-ICU). Previous validation of the CAM-ICU for use in the ED showed varying results, possibly because it was administered at different or unknown time points. The aim was to study the prevalence of delirium in older ( ≥ 70 years) ED patients using the CAM-ICU and 6-CIT. PARTICIPANTS AND METHODS: A prospective cohort study was carried out in one tertiary care and one secondary care hospital in the Netherlands. Patients aged 70 years and older attending the ED were included. Delirium screening was performed within 1 h after ED registration using the CAM-ICU. The 6-CIT was determined for comparison using a cut-off point of at least 14 points indicating possible delirium. RESULTS: A total of 997 patients were included in the study, with a median age of 78 years (interquartile range 74-84). Delirium as assessed with CAM-ICU was positive in only 13 (1.3%, 95% confidence interval: 0.8-2.2) patients. Ninety-five (9.5% 95% confidence interval: 7.9-11.5) patients had 6-CIT more than or equal to 14. CONCLUSION: We found a delirium prevalence of 1.3% using the CAM-ICU, which was much lower than the expected prevalence of around 10% as being frequently reported in the literature and what we found when using the 6-CIT. On the basis of these results, caution is warranted to use the CAM-ICU for early screening in the ED.