Evaluation of the clinical relevance of the Biofire© FilmArray pneumonia panel among hospitalized patients.

PURPOSE: Panel PCR tests provide rapid pathogen identification. However, their diagnostic performance is unclear. We assessed the performance of the Biofire© FilmArray pneumonia (PN)-panel against standard culture in broncho-alveolar lavage (BAL) samples. METHODS: Setting: University Hospital Basel (February 2019 to July 2020), including hospitalized patients with a BAL (± pneumonia). We determined sensitivity and specificity of the PN-panel against standard culture. Using univariate logistic regression, we calculated odds ratios (OR) for pneumonia according to PN-panel and culture status, stratifying by chronic pulmonary disease. We calculated ORs for pneumonia for different pathogens to estimate the clinical relevance. RESULTS: We included 840 adult patients, 60% were males, median age was 68 years, 35% had chronic pulmonary disease, 21% had pneumonia, and 36% had recent antibiotic use. In 1078 BAL samples, bacterial pathogens were detected in 36% and 16% with PN-panel and culture, respectively. The overall sensitivity and specificity of the PN-panel was high, whereas the positive predictive value was low. The OR of pneumonia was 1.1 (95% CI 0.7-1.6) for PN-panel-positive only; 2.6 (95% CI 1.3-5.3) for culture-positive only, and 1.6 (95% CI 1.0-2.4) for PN-panel and culture-positive. The detection rate of Haemophilus influenzae, Staphylococcus aureus, and Moraxella catarrhalis in the PN-panel was high but not associated with pneumonia. CONCLUSION: While sensitivity and specificity of PN-panel are high compared to culture, pathogen detection did not correlate well with a pneumonia diagnosis. Patients with culture-positive BAL had the highest OR for pneumonia-thus the impact of the PN-panel on clinical management needs further evaluation in randomized controlled trials.

Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19.

Rationale: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome with fatal outcomes. Evidence suggests that dysregulated immune responses, including autoimmunity, are key pathogenic factors. Objectives: To assess whether IgA autoantibodies target lung-specific proteins and contribute to disease severity. Methods: We collected 147 blood, 9 lung tissue, and 36 BAL fluid samples from three tertiary hospitals in Switzerland and one in Germany. Severe COVID-19 was defined by the need to administer oxygen. We investigated the presence of IgA autoantibodies and their effects on pulmonary surfactant in COVID-19 using the following methods: immunofluorescence on tissue samples, immunoprecipitations followed by mass spectrometry on BAL fluid samples, enzyme-linked immunosorbent assays on blood samples, and surface tension measurements with medical surfactant. Measurements and Main Results: IgA autoantibodies targeting pulmonary surfactant proteins B and C were elevated in patients with severe COVID-19 but not in patients with influenza or bacterial pneumonia. Notably, pulmonary surfactant failed to reduce surface tension after incubation with either plasma or purified IgA from patients with severe COVID-19. Conclusions: Our data suggest that patients with severe COVID-19 harbor IgA autoantibodies against pulmonary surfactant proteins B and C and that these autoantibodies block the function of lung surfactant, potentially contributing to alveolar collapse and poor oxygenation.

SARS-CoV-2 outbreak in a tri-national urban area is dominated by a B.1 lineage variant linked to a mass gathering event.

The first case of SARS-CoV-2 in Basel, Switzerland was detected on February 26th 2020. We present a phylogenetic study to explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26th until March 23rd. We sequenced SARS-CoV-2 naso-oropharyngeal swabs from 746 positive tests that were performed at the University Hospital Basel during the study period. We successfully generated 468 high quality genomes from unique patients and called variants with our COVID-19 Pipeline (COVGAP), and analysed viral genetic diversity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. Epidemiological data from patient questionnaires was used to facilitate the interpretation of phylogenetic observations. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected first on March 2nd, although the first sample identified belonged to B.1.1. Within B.1, 68·2% of our samples fall within a clade defined by the SNP C15324T ('Basel cluster'), including 157 identical sequences at the root of the 'Basel cluster', some of which we can specifically trace to regional spreading events. We infer the origin of B.1-C15324T to mid-February in our tri-national region. The other genomes map broadly over the global phylogenetic tree, showing several introduction events from and/or dissemination to other regions of the world via travellers. Family transmissions can also be traced in our data. A single lineage variant dominated the outbreak in the Basel area while other lineages, such as the first (B.1.1), did not propagate. A mass gathering event was the predominant initial source of cases, with travel returners and family transmissions to a lesser extent. We highlight the importance of adding specific questions to epidemiological questionnaires, to obtain data on attendance of large gatherings and their locations, as well as travel history, to effectively identify routes of transmissions in up-coming outbreaks. This phylogenetic analysis in concert with epidemiological and contact tracing data, allows connection and interpretation of events, and can inform public health interventions. Trial Registration: ClinicalTrials.gov NCT04351503.

Identification of microorganisms by a rapid PCR panel from positive blood cultures leads to faster optimal antimicrobial therapy - a before-after study.

BACKGROUND: The BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) detects microorganisms with high accuracy in positive blood cultures (BC) - a key step in the management of patients with suspected bacteraemia. We aimed to compare the time to optimal antimicrobial therapy (OAT) for the BF-FA-BCIP vs. standard culture-based identification. METHODS: In this retrospective single-centre study with a before-after design, 386 positive BC cases with identification by BF-FA-BCIP were compared to 414 controls with culture-based identification. The primary endpoint was the time from BC sampling to OAT. Secondary endpoints were time to effective therapy, length of stay, (re-)admission to ICU, in-hospital and 30-day mortality. Outcomes were assessed using Cox proportional hazard models and logistic regressions. RESULTS: Baseline characteristics of included adult inpatients were comparable. Main sources of bacteraemia were urinary tract and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7%, for cases and controls, respectively). Median (95%CI) time to OAT was 25.5 (21.0-31.2) hours with BF-FA-BCIP compared to 45.7 (37.7-51.4) hours with culture-based identification. We observed no significant difference for secondary outcomes. CONCLUSIONS: Rapid microorganism identification by BF-FA-BCIP was associated with a median 20-h earlier initiation of OAT in patients with positive BC. No impact on length of stay and mortality was noted. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04156633, registered on November 5, 2019.

Emergency Presentations for Dizziness-Radiological Findings, Final Diagnoses, and Mortality.

Background: Dizziness is a frequent presentation in patients presenting to emergency departments (EDs), often triggering extensive work-up, including neuroimaging. Therefore, gathering knowledge on final diagnoses and outcomes is important. We aimed to describe the incidence of dizziness as primary or secondary complaint, to list final diagnoses, and to determine the use and yield of neuroimaging and outcomes in these patients. Methods: Secondary analysis of two observational cohort studies, including all patients presenting to the ED of the University Hospital of Basel from 30th January 2017-19th February 2017 and from 18th March 2019-20th May 2019. Baseline demographics, Emergency Severity Index (ESI), hospitalization, admission to Intensive Care Units (ICUs), and mortality were extracted from the electronic health record database. At presentation, patients underwent a structured interview about their symptoms, defining their primary and secondary complaints. Neuroimaging results were obtained from the picture archiving and communication system (PACS). Patients were categorized into three non-overlapping groups: dizziness as primary complaint, dizziness as secondary complaint, and absence of dizziness. Results: Of 10076 presentations, 232 (2.3%) indicated dizziness as their primary and 984 (9.8%) as their secondary complaint. In dizziness as primary complaint, the three (out of 73 main conditions defined) main diagnoses were nonspecific dizziness (47, 20.3%), dysfunction of the peripheral vestibular system (37, 15.9%), as well as somatization, depression, and anxiety (20, 8.6%). 104 of 232 patients (44.8%) underwent neuroimaging, with relevant findings in 5 (4.8%). In dizziness as primary complaint 30-day mortality was 0%. Conclusion: Work-up for dizziness in emergency presentations has to consider a broad differential diagnosis, but due to the low yield, it should include neuroimaging only in few and selected cases, particularly with additional neurological abnormalities. Presentation with primary dizziness carries a generally favorable prognosis lacking short-term mortality. .

Validation of a Simple Score for Mortality Prediction in a Cohort of Unselected Emergency Patients.

Background: Prognostication is an important component of medical decision-making. A patients' general prognosis can be difficult to measure. The Simple Prognostic Score (SPS) was designed to include patients' age, mobility, aggregated vital signs, and the treating physician's decision to admit to aid prognostication. Study Aim. Our study aim is to validate the SPS, compare it with the Emergency Severity Index (ESI) regarding its prognostic performance, and test the interrater reliability of the subjective variable of the decision to admit. Methods: Over a period of 9 weeks all patients presenting to the ED were included, routinely interviewed, final disposition registered, and followed up for one year. The C-statistics of discrimination was used to compare SPS and ESI predictions of 7-day, 30-day, and 1-year mortality. Youden J Statistics and Odds ratio, using logistical regression, were calculated for the Simple Prognostic Score. In a subset, a chart review was performed by senior physicians for a secondary assessment of the decision to admit. Interrater reliability was calculated using percentages and Cohens Kappa. Results: Out of 5648 patients, 3272 (57.9%) had a low SPS (i.e., ≤ 1); none of these patients died within 7 days, 2 (0.1%) died within 30 days after presentation and 19 (0.6%) died within a year. The area under the curve for 1-year mortality of the Simple Prognostic Score was 0.848. Secondary analysis of the interrater agreement for the decision to admit was 92%. Conclusion: In a prospective study of unselected ED patients, the Simple Prognostic Score was validated as a reliable predictor of short- and long-term mortality.

Comparing Immunoassays for SARS-CoV-2 Antibody Detection in Patients with and without Laboratory-Confirmed SARS-CoV-2 Infection.

Commercially available SARS-CoV-2-directed antibody assays may assist in diagnosing past exposure to SARS-CoV-2 antigens. We cross-compared the following eight immunoassays detecting antibodies against SARS-CoV-2 nucleocapsid (N) or spike (S) antigens in three cohorts consisting of 859 samples from 622 patients: (#1) EDI novel coronavirus COVID-19 (Epitope), (#2) RecomWell SARS-CoV-2 (Mikrogen), (#3) COVID-19 ELISA (VirCell), (#4) Elecsys anti-SARS-CoV-2 N (Roche), (#5) Liaison SARS-CoV-2 S1/S2 (DiaSorin), (#6) anti-SARS-CoV-2 ELISA (EuroImmun), (#7) Elecsys anti-SARS-CoV-2 S (Roche), and (#8) Liaison SARS-CoV-2 TrimericS (DiaSorin). In cross-sectional cohort 1 (68 sera from 38 patients with documented SARS-CoV-2 infection), agreement between assays #1 to #6 ranged from 75% to 93%, whereby discordance mostly resulted from N-based assays #1 to #4. In cross-sectional cohort 2 (510 sera from 510 patients; 56 documented, 454 unknown SARS-CoV-2 infection), assays #4 to #6 were analyzed further together with assays #7 and #8, revealing 94% concordance (44 [9%] positives and 485 [85%] negatives). Discordance was highest within 2 weeks after SARS-CoV-2/COVID-19 diagnosis and confirmed in the longitudinal cohort 3 (281 sera from 74 COVID-19 patients), using assays #4, #6, #7, and #8. Subanalysis of 20 (27%) initially seronegative cohort 3 patients revealed assay-dependent 50% and 90% seroconversion rates after 8 to 11 days and 14 to 18 days, respectively. Increasing SARS-CoV-2 antibodies were significantly associated with declining levels of viral loads, lactate dehydrogenase, interleukin-6, and C-reactive protein and preceded clearance of SARS-CoV-2 detection in the upper respiratory tract by approximately 1 week. SARS-CoV-2-specific antibody assays show substantial agreement, but interpretation of qualitative and semiquantitative results depends on the time elapsed postdiagnosis and the choice of viral antigen. Mounting of systemic SARS-CoV-2-specific antibodies may predict recovery from viral injury and clearance of mucosal replication.

Epidemiology and precision of SARS-CoV-2 detection following lockdown and relaxation measures.

OBJECTIVES: Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to the clinical and epidemiological assessment of CoVID-19. We cross-validated manual and automated high-throughput testing for SARS-CoV-2-RNA, evaluated SARS-CoV-2 loads in nasopharyngeal-oropharyngeal swabs (NOPS), lower respiratory fluids, and plasma, and analyzed detection rates after lockdown and relaxation measures. METHODS: Basel-S-gene, Roche-E-gene, and Roche-cobas®6800-Target1 and Target2 were prospectively validated in 1344 NOPS submitted during the first pandemic peak (Week 13). Follow-up cohort (FUP) 1, 2, and 3 comprised 10,999, 10,147, and 19,389 NOPS submitted during a 10-week period until Weeks 23, 33, and 43, respectively. RESULTS: Concordant results were obtained in 1308 cases (97%), including 97 (9%) SARS-CoV-2-positives showing high quantitative correlations (Spearman's r > .95; p < .001) for all assays and high precision by Bland-Altman analysis. Discordant samples (N = 36, 3%) had significantly lower SARS-CoV-2 loads (p < .001). Following lockdown, detection rates declined to <1% in FUP-1, reducing single-test positive predictive values from 99.3% to 85.1%. Following relaxation, rates flared up to 4% and 12% in FUP-2 and -3, but infected patients were younger than during lockdown (34 vs. 52 years, p < .001). In 261 patients providing 936 NOPS, SARS-CoV-2 loads declined by three orders of magnitude within 10 days postdiagnosis (p < .001). SARS-CoV-2 loads in NOPS correlated with those in time-matched lower respiratory fluids or in plasma but remained detectable in some cases with negative follow-up NOPS, respectively. CONCLUSION: Manual and automated assays significantly correlated qualitatively and quantitatively. Following a successful lockdown, declining positive predictive values require independent dual-target confirmation for reliable assessment. Confirmatory and quantitative follow-up testing should be obtained within <5 days and consider lower respiratory fluids in symptomatic patients with SARS-CoV-2-negative NOPS.

Disagreements between emergency patients and physicians regarding chief complaint - Patient factors and prognostic implications.

INTRODUCTION: The predictive power of chief complaints reported at presentation to the emergency department (ED) is well known. However, there is a lack of research on the coherence of patient versus physician reported chief complaints. The aim of this study was to determine the rate of disagreement between patients and physicians regarding chief complaint and its significance for the prediction of the outcomes number of resources used during ED work-up, hospitalisation, ICU admission, in-hospital mortality and hospital length of stay. METHODS: In this secondary analysis of a study conducted over a time course of 9 weeks, consecutive emergency patients and their physicians were independently asked to report the chief complaint upon presentation. The two reports were assessed for pair-wise agreement. RESULTS: Of 6722 emergency patients (mean age 53.3, 46.8% female), the median number of symptoms reported by patients was two and one reported by physicians. The rate of disagreement on chief complaints was 32.6%. Disagreement was associated with a higher number of resources (ß = 0.24; CI, 0.18, 0.31, P <.001) and hospitalisation (OR = 1.31; CI, 1.16, 1.48, P <.001), using multivariable analyses. Patient factors associated with disagreement were age (OR = 1.01; CI, 1.01, 1.01, P <.001), number of patient reported symptoms (OR = 1.27; CI, 1.23, 1.32, P <.001) and male gender (OR = 1.12; 1.01, 1.25, P =.0285). CONCLUSION: Disagreement on chief complaint between patient and physician may be an early marker for a complex work-up, requiring more resources and hospitalisations. The relevance of this finding is the newly identified signal of chief complaint replacement. It is easy to identify and should generate attention, as it affects a certain phenotype (older male patients with higher numbers of complaints).

Contact-Free Monitoring of Pulse Rate For Triage of Patients Presenting to the Emergency Department.

BACKGROUND: The evaluation of a patient's pulse rate (PR) plays a key role in emergency triage and is commonly measured in a contact-dependent way. OBJECTIVE: Our aims were to evaluate a camera-based prototype application (CBPA) measuring PR in an emergency department (ED) as an alternative to the current contact-dependent method of pulse oximetry and to determine the correlation between CBPA and pulse oximetry in measuring PR. METHODS: We simultaneously measured PR with CBPA and pulse oximetry as a reference method on a large group of ED walk-in patients. We then estimated correlation and agreement between the two methods, as well as the corresponding 95% confidence intervals. RESULTS: In a convenience sample of 446 patients, the correlation between CBPA and pulse oximetry in measuring PR was 0.939 (95% confidence interval [CI] 0.927-0.949) and the intraclass correlation was 0.939 (95% CI 0.927-0.949). CONCLUSIONS: Our study found that CBPA seems to be a viable alternative to the current method of measuring PR at triage. ClinicalTrials.gov identifier: NCT03393585.

Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 Emergence Amidst Community-Acquired Respiratory Viruses.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China as the cause of coronavirus disease 2019 in December 2019 and reached Europe by late January 2020, when community-acquired respiratory viruses (CARVs) are at their annual peak. We validated the World Health Organization (WHO)-recommended SARS-CoV-2 assay and analyzed the epidemiology of SARS-CoV-2 and CARVs. METHODS: Nasopharyngeal/oropharyngeal swabs (NOPS) from 7663 patients were prospectively tested by the Basel S-gene and WHO-based E-gene (Roche) assays in parallel using the Basel N-gene assay for confirmation. CARVs were prospectively tested in 2394 NOPS by multiplex nucleic acid testing, including 1816 (75%) simultaneously for SARS-CoV-2. RESULTS: The Basel S-gene and Roche E-gene assays were concordant in 7475 cases (97.5%) including 825 (11%) SARS-CoV-2 positives. In 188 (2.5%) discordant cases, SARS-CoV-2 loads were significantly lower than in concordant positive ones and confirmed in 105 (1.4%). Adults were more frequently SARS-CoV-2 positive, whereas children tested more frequently CARV positive. CARV coinfections with SARS-CoV-2 occurred in 1.8%. SARS-CoV-2 replaced CARVs within 3 weeks, reaching 48% of all detected respiratory viruses followed by rhinovirus/enterovirus (13%), influenza virus (12%), coronavirus (9%), respiratory syncytial virus (6%), and metapneumovirus (6%). CONCLUSIONS: Winter CARVs were dominant during the early SARS-CoV-2 pandemic, impacting infection control and treatment decisions, but were rapidly replaced, suggesting competitive infection. We hypothesize that preexisting immune memory and innate immune interference contribute to the different SARS-CoV-2 epidemiology among adults and children.

Validation of the Clinical Frailty Scale for Prediction of Thirty-Day Mortality in the Emergency Department.

STUDY OBJECTIVE: We validate the Clinical Frailty Scale by examining its independent predictive validity for 30-day mortality, ICU admission, and hospitalization and by determining its reliability. We also determine frailty prevalence in our emergency department (ED) as measured with the Clinical Frailty Scale. METHODS: This was a prospective observational study including consecutive ED patients aged 65 years or older, from a single tertiary care center during a 9-week period. To examine predictive validity, association with mortality was investigated through a Cox proportional hazards regression; hospitalization and ICU transfer were investigated through multivariable logistic regression. We assessed reliability by calculating Cohen's weighted κ for agreement of experts who independently assigned Clinical Frailty Scale levels, compared with trained study assistants. Frailty was defined as a Clinical Frailty Scale score of 5 and higher. RESULTS: A total of 2,393 patients were analyzed in this study, of whom 128 died. Higher frailty levels were associated with higher hazards for death independent of age, sex, and condition (medical versus surgical). The area under the curve for 30-day mortality prediction was 0.81 (95% confidence interval [CI] 0.77 to 0.85), for hospitalization 0.72 (95% CI 0.70 to 0.74), and for ICU admission 0.69 (95% CI 0.66 to 0.73). Interrater reliability between the reference standard and the study team was good (weighted Cohen's κ was 0.74; 95% CI 0.64 to 0.85). Frailty prevalence was 36.8% (n=880). CONCLUSION: The Clinical Frailty Scale appears to be a valid and reliable instrument to identify frailty in the ED. It might provide ED clinicians with useful information for decisionmaking in regard to triage, disposition, and treatment.

Delayed Diagnosis in Pulmonary Embolism: Frequency, Patient Characteristics, and Outcome.

BACKGROUND: The incidence and the outcomes of pulmonary embolism (PE) missed during emergency department (ED) workup are largely unknown. OBJECTIVES: To describe the frequency, demographics, and outcomes of patients with delayed diagnosis of PE. METHODS: We retrospectively compared patients diagnosed with PE during ED workup (early diagnosis) with patients diagnosed with PE thereafter (delayed diagnosis). Electronic health records (EHR) of 123,560 consecutive patients who attended a tertiary hospital ED were screened. Data were matched with radiology and pathology results from the EHR. RESULTS: Of 1,119 patients presenting to the ED with early workup for PE, PE was diagnosed in 182 patients (80.5%) as early diagnosis. Delayed diagnosis was established in 44 cases (19.5%) using radiology and/or autopsy data. Median age of patients with early diagnosis was significantly lower as compared to delayed diagnosis (67 vs. 77.5 years). Main symptoms were dyspnea (109 patients [59.9%] in early, 20 patients [45.5%] in delayed diagnosis), chest pain (90 patients [49.5%] in early, 8 patients [18.2%] in delayed diagnosis), and nonspecific complaints (16 patients [8.8%] in early, 13 patients [29.5%] in delayed diagnosis). In-hospital mortality was 1.6% in early diagnosis and 43.2% in delayed diagnosis. CONCLUSIONS: Delayed diagnosis of PE carries a worse prognosis than early diagnosis. This discrepancy may arise from either delayed therapy, confounding variables (e.g., older age), or both. Possible reasons for delayed diagnoses are nonspecific presentations and symptoms overlapping with preexisting conditions.

A simple prognostic score predicts one-year mortality of alert and calm emergency department patients: A prospective two-center observational study.

STUDY OBJECTIVE: To derive and validate a prognostic score to predict 1-year mortality using vital signs, mobility and other variables that are readily available at the bedside at no additional cost. METHODS: Post hoc analysis of two independent prospective observational studies in two emergency departments, one in Denmark and the other in Switzerland. PARTICIPANTS: Alert and calm emergency department patients. MEASUREMENTS: The prediction of mortality from presentation to 365 days by vital signs, mobility and other variables that are readily available at the bedside at no additional cost. RESULTS: One thousand six hundred and eighteen alert and calm patients were in the Danish cohort and 1331 in the Swiss cohort. Logistic regression identified age >68 years, abnormal vital signs, impaired mobility and the decision to admit as significant predictors of 365-day mortality. A simple prognostic score awarded one point to each of these predictors. Less than two of these predictors were present in 45.6% of patients, and only 0.4% of these patients died within a year. If two or more of these predictors were present, 365-day mortality increased exponentially. CONCLUSION: Age >68 years, the decision for hospital admission, any vital sign abnormality at presentation and impaired mobility at presentation are equally powerful predictors of 1-year mortality in alert and calm emergency department patients. If validated by others these predictors could be used to discharge patients with confidence since nearly half of these patients had less than two predictors and none of them died within 30 days. However, when two or more predictors were present 365-day mortality increased exponentially.

Inflammatory Biomarkers and Clinical Judgment in the Emergency Diagnosis of Urgent Abdominal Pain.

BACKGROUND: The early diagnosis of urgent abdominal pain (UAP) is challenging. Most causes of UAP are associated with extensive inflammation. Therefore, we hypothesized that quantifying inflammation using interleukin-6 and/or procalcitonin would provide incremental value in the emergency diagnosis of UAP. METHODS: This was an investigator-initiated prospective, multicenter diagnostic study enrolling patients presenting to the emergency department (ED) with acute abdominal pain. Clinical judgment of the treating physician regarding the presence of UAP was quantified using a visual analog scale after initial clinical and physician-directed laboratory assessment, and again after imaging. Two independent specialists adjudicated the final diagnosis and the classification as UAP (life-threatening, needing urgent surgery and/or hospitalization for acute medical reasons) using all information including histology and follow-up. Interleukin-6 and procalcitonin were measured blinded in a central laboratory. RESULTS: UAP was adjudicated in 376 of 1038 (36%) patients. Diagnostic accuracy for UAP was higher for interleukin-6 [area under the ROC curve (AUC), 0.80; 95% CI, 0.77-0.82] vs procalcitonin (AUC, 0.65; 95% CI, 0.62-0.68) and clinical judgment (AUC, 0.69; 95% CI, 0.65-0.72; both P < 0.001). Combined assessment of interleukin-6 and clinical judgment increased the AUC at presentation to 0.83 (95% CI, 0.80-0.85) and after imaging to 0.87 (95% CI, 0.84-0.89) and improved the correct identification of patients with and without UAP (net improvement in mean predicted probability: presentation, +19%; after imaging, +15%; P < 0.001). Decision curve analysis documented incremental value across the full range of pretest probabilities. A clinical judgment/interleukin-6 algorithm ruled out UAP with a sensitivity of 97% and ruled in UAP with a specificity of 93%. CONCLUSIONS: Interleukin-6 significantly improves the early diagnosis of UAP in the ED.

Optimizing the month of the year backwards test for delirium screening of older patients in the emergency department.

INTRODUCTION: Different scoring methods exist for the Month of the Year Backward Test (MBT), which is designed to detect inattention, the core feature of delirium. When used as a part of the modified Confusion Assessment Method for the Emergency Department (mCAM-ED), each error in the MBT scores one point. Because this scoring procedure is complex, we aimed to simplify the scoring method of the MBT. METHODS: This is a secondary analysis of a single center prospective validation study of the mCAM-ED comprising a sample of Emergency Department (ED) patients aged 65 or older presenting to our ED. DATA COLLECTION: Research assistants (RAs) who were trained nurses conducted the MBT. Geriatricians conducted the reference standard delirium assessment within 1 h of the RA. RESULTS: For the scoring method "number of errors", optimal performance according the Youden index was achieved when 8 or more errors were reached resulting in an overall sensitivity of 0.95 and overall specificity of 0.94. The scoring method "number of errors in combination with time needed" resulted in a comparable result with minimally lower positive likelihood ratios. For the scoring method "last month in correct order", optimal performance according the Youden index was achieved with the month of September resulting in an overall sensitivity of 0.90 and an overall specificity of 0.89. DISCUSSION: We suggest omitting the factor time and using a more practical scoring method with good performance: "last month in correct order" with the requirement to reach September to rule out delirium.

Clinical Scores and Formal Triage for Screening of Sepsis and Adverse Outcomes on Arrival in an Emergency Department All-Comer Cohort.

BACKGROUND: Early recognition of sepsis remains a major challenge. The clinical utility of the Quick Sepsis-Related Organ Failure Assessment (qSOFA) score is still undefined. Several studies have tested its prognostic value. However, its ability to diagnose sepsis is still unknown. OBJECTIVE: Our aim was to compare the performance of qSOFA, systemic inflammatory response syndrome (SIRS) criteria, National Early Warning Score (NEWS), and formal triage with the Emergency Severity Index (ESI) algorithm to identify patients with sepsis and predict adverse outcomes on arrival in an emergency department (ED) all-comer cohort. METHODS: We included all patients presenting consecutively to the ED during a 3-week period. We used vital signs recorded at triage to calculate the study scores. Two independent assessors retrospectively assigned the primary outcome of sepsis according to Third International Consensus Definitions for Sepsis and Septic Shock criteria in a chart review process. RESULTS: There were 2523 cases included in the analysis and 39 (1.6%) had the primary outcome of sepsis. The area under the curve for sepsis was 0.79 (95% confidence interval [CI] 0.71-0.86) for qSOFA, 0.81 (95% CI 0.73-0.87) for SIRS, 0.85 (95% CI 0.77-0.92) for NEWS, and 0.77 (95% CI 0.70-0.83) for ESI. CONCLUSIONS: qSOFA offered high specificity for the prediction of sepsis and adverse outcomes. However, its low sensitivity does not support widespread use as a screening tool for sepsis. NEWS outperformed qSOFA for prediction of adverse outcomes and screening for sepsis.

A Prospective Evaluation of Point of Care Ultrasound Teaching in Switzerland.

CONTEXT: As the utility of point-of-care ultrasound (POCUS) continues to expand in the medical field, there is a need for effective educational methods. In Switzerland, medical education follows the European model and lasts 6 years, focusing on preclinical training during the first 2 years. No previous studies have evaluated the optimal time for teaching ultrasound in European medical education. AIMS: The aim of this study is to provide ultrasound training to medical students in Switzerland at varying times during their clinical training to determine if the level of training plays a role in their ability to comprehend and to apply basic POCUS skills. METHODS: We performed an observational study utilizing a convenience sample of Swiss medical students between July 11, 2016 and August 6, 2016. They were taught a 2-day POCUS course by five American-trained 1st-year medical students. Following this course, students were evaluated with written and clinical examination. RESULTS: 100 Swiss medical students were enrolled in the study. A total of 59 of these students were early clinical students, and 41 students were late clinical students. A two-tailed t-test was performed and demonstrated that the late clinical students performed better than the early clinical students on the written assessment; however, no difference was found in clinical skill. CONCLUSION: Our data suggest that Swiss medical students can learn and perform POCUS after a 2-day instructional taught by trained 1st-year American medical students. No difference was found between students in early clinical training and late clinical training for the ability to perform POCUS.

Symptoms at presentation to the emergency department: Predicting outcomes and changing clinical practice?

BACKGROUND: The type and number of symptoms in emergency patients differ widely. It remains unclear, if outcomes can be predicted by the number of symptoms. Furthermore, it is unknown, whether clinical practice could be influenced by presenting symptoms. METHODS: Prospective observational study, performed in the emergency department of the University Hospital Basel, a tertiary hospital. A consecutive sample of patients was interviewed at presentation for a predefined set of 35 symptoms. The number of symptoms was correlated with outcomes using linear and logistic regression models. Clinical practice was observed using prospective data on disease severity ratings, triage category, use of resources, length-of-stay and follow-up presentations. RESULTS: Data of 3472 patients were analysed. The number of symptoms ranged between 1 and 25, the mean being 2.74. Women reported more symptoms than men. Age and comorbidity indices were not associated with the number of symptoms. After adjusting for age and gender, there was no correlation between the number of symptoms and adverse outcomes, such as ICU-admission or in-hospital mortality (OR: 1.03, CI: 0.88-1.18, P = .68). The number of symptoms at presentation was associated with hospitalisation, disease severity rating by patients and emergency physicians, triage categories, use of resources, length-of-stay and follow-up presentations. CONCLUSION: The number of symptoms did not correlate with the main adverse outcomes (ICU-admission and in-hospital mortality). However, clinical practice was influenced by the nature and number of symptoms. This was shown by associations with hospitalisation, length-of-stay, use of resources and follow-up presentations. Furthermore, the number of symptoms correlated with the caregivers' disease severity ratings and the attributed triage categories. This may indicate that caregivers respond to the number of symptoms by a higher investment in their immediate work-ups and later follow-ups.