Multicentre external validation of the Canadian Syncope Risk Score to predict adverse events and comparison with clinical judgement.

BACKGROUND: The Canadian Syncope Risk Score (CSRS) has been proposed for syncope risk stratification in the emergency department (ED). The aim of this study is to perform an external multicenter validation of the CSRS and to compare it with clinical judgement. METHODS: Using patients previously included in the SyMoNE database, we enrolled subjects older than 18 years who presented reporting syncope at the ED. For each patient, we estimated the CSRS and recorded the physician judgement on the patients' risk of adverse events. We performed a 30-day follow-up. RESULTS: From 1 September 2015 to 28 February 2017, we enrolled 345 patients; the median age was 71 years (IQR 51-81), 174 (50%) were men and 29% were hospitalised. Serious adverse events occurred in 43 (12%) of the patients within 30 days. The area under the curve of the CSRS and clinical judgement was 0.75 (95% CI 0.68 to 0.81) and 0.68 (95% CI 0.61 to 0.74), respectively. The risk of adverse events of patients at low risk according to the CSRS and clinical judgement was 6.7% and 2%, with a sensitivity of 70% (95% CI 54% to 83%) and 95% (95% CI 84% to 99%), respectively. CONCLUSION: This study represents the first validation analysis of CSRS outside Canada. The overall predictive accuracy of the CSRS is similar to the clinical judgement. However, patients at low risk according to clinical judgement had a lower incidence of adverse events as compared with patients at low risk according to the CSRS. Further studies showing that the adoption of the CSRS improve patients' outcomes is warranted before its widespread implementation.

Procalcitonin-guided antibiotic therapy: an expert consensus.

BACKGROUND: Procalcitonin (PCT) is a useful biomarker of bacterial infection and its use is associated to reduced duration of antibiotic therapy in the setting of intensive care medicine. To address the need of practical guidance for the use of PCT in various clinical settings, a group of experts was invited to participate at a consensus process with the aims of defining the rationale for appropriate use of PCT and for improving the management of critically ill patients with sepsis. METHODS: A group of 14 experts from anesthesiology and critical care, infectious diseases, internal medicine, pulmonology, clinical microbiology, laboratory medicine, clinical pharmacology and methodology provided expert opinion through a modified Delphi process, after a comprehensive literature review. RESULTS: The appropriateness of use of PCT in terms of diagnosis, prognosis and antimicrobial stewardship was assessed for different scenarios or settings such us management of infection in the emergency department, regular wards, surgical wards or in the intensive care unit. Similarly, appropriateness and timing of PCT measurement were evaluated. All the process consisted in three Delphi rounds. CONCLUSIONS: PCT use is appropriate in algorithms for antibiotic de-escalation and discontinuation. In this case, reproducible, high sensitive assays should be used. However, initiation or escalation of antibiotic therapy in specific scenarios, including acute respiratory infections, should not be based solely on PCT serum levels. Clinical and radiological findings, evaluation of severity of illness and of patient's characteristics should be taken into proper account in order to correctly interpret PCT results.

Neural networks as a tool to predict syncope risk in the Emergency Department.

AIMS: There is no universally accepted tool for the risk stratification of syncope patients in the Emergency Department. The aim of this study was to investigate the short-term predictive accuracy of an artificial neural network (ANN) in stratifying the risk in this patient group. METHODS AND RESULTS: We analysed individual level data from three prospective studies, with a cumulative sample size of 1844 subjects. Each dataset was reanalysed to reduce the heterogeneity among studies defining abnormal electrocardiogram (ECG) and serious outcomes according to a previous consensus. Ten variables from patient history, ECG, and the circumstances of syncope were used to train and test the neural network. Given the exploratory nature of this work, we adopted two approaches to train and validate the tool. One approach used 4/5 of the data for the training set and 1/5 for the validation set, and the other approach used 9/10 for the training set and 1/10 for the validation set. The sensitivity, specificity, and area under the receiver operating characteristic curve of ANNs in identifying short-term adverse events after syncope were 95% [95% confidence interval (CI) 80-98%], 67% (95% CI 62-72%), 0.69 with the 1/5 approach and 100% (95% CI 84-100%), 79% (95% CI 72-85%), 0.78 with the 1/10 approach. CONCLUSION: The results of our study suggest that ANNs are effective in predicting the short-term risk of patients with syncope. Prospective studies are needed in order to compare ANNs' predictive capability with existing rules and clinical judgment.

Priorities for emergency department syncope research.

STUDY OBJECTIVES: There is limited evidence to guide the emergency department (ED) evaluation and management of syncope. The First International Workshop on Syncope Risk Stratification in the Emergency Department identified key research questions and methodological standards essential to advancing the science of ED-based syncope research. METHODS: We recruited a multinational panel of syncope experts. A preconference survey identified research priorities, which were refined during and after the conference through an iterative review process. RESULTS: There were 31 participants from 7 countries who represented 10 clinical and methodological specialties. High-priority research recommendations were organized around a conceptual model of ED decisionmaking for syncope, and they address definition, cohort selection, risk stratification, and management. CONCLUSION: We convened a multispecialty group of syncope experts to identify the most pressing knowledge gaps and defined a high-priority research agenda to improve the care of patients with syncope in the ED.

D-dimer testing for suspected venous thromboembolism in the emergency department. Consensus document of AcEMC, CISMEL, SIBioC, and SIMeL.

D-dimer testing is currently considered a cornerstone in the diagnostic approach of patients with suspected venous thromboembolism (VTE) across different health-care settings, including the emergency department (ED). Nevertheless, inappropriate or incorrect activities developing throughout the total testing process may substantially impair the clinical usefulness of this test and delay or even challenge the fast rule out or diagnosis of VTE. The leading problem of D-dimer is represented by the poor specificity for diagnosing VTE, wherein a minority of patients with a positive D-dimer are finally diagnosed with VTE, and even more importantly, the specificity further decreases with ageing, thus contributing to increase the overcrowding in short stay units such as the ED. Due to the large heterogeneity that characterizes the use of D-dimer in the emergency room, three Italian societies of laboratory medicine (Italian Committee for Standardization of Hematology and Laboratory Methods, Italian Society of Clinical Biochemistry and Molecular Biology, and Italian Society of Laboratory Medicine), along with the Academy of Emergency Medicine and Care, have developed a consensus document about the use of D-dimer testing for diagnostics of patients with suspected VTE in this health-care setting. The evidence-based indications contained in this document will cover the leading preanalytical, analytical, and postanalytical issues that may impair the clinical efficacy of D-dimer testing in the ED.

Proposal for the use in emergency departments of cardiac troponins measured with the latest generation methods in patients with suspected acute coronary syndrome without persistent ST-segment elevation.

UNLABELLED: The purpose of this document is to develop recommendations on the use of the latest generation of cardiac troponins in emergency room settings for the diagnosis of myocardial infarction in patients with suspected acute coronary syndrome (ACS) without persistent ST-segment elevation (NSTE-ACS). The main points which have been addressed reaching a consensus are represented by: Suitability and appropriateness of the terminology. Appropriateness of the request. Confirmation of the diagnosis of myocardial infarction (rule-in). Exclusion of the diagnosis of myocardial infarction (rule-out). WORK METHOD: Each point has been analyzed by taking into account the evidence presented in medical publications. Recommendations were developed using the criteria adopted by the European Society of Cardiology and the American Heart Association/American College of Cardiology (www.escardio.org/guidelines). Each point of the recommendation was submitted for validation to an external audit by a Group of Experts (named above).

Current ED syncope management in Italian hospitals and prospects for optimization: a national survey.

To investigate current ED management of patients with syncope in Italy and opportunities for optimization, we carried out a questionnaire survey involving 102 directors of ED facilities in our country, of any complexity level, with 55.9% located in the North, 97% equipped with an ED Observation Unit (EDOU), and 21.8% with an outpatient Syncope Unit (SU). 43.6% of EDs management is not standardized. Clinical judgment and monitoring are the main factors leading management while old age and neuropsychic comorbidities the most hindering it. More than one third of ED facilities treats fewer than half of patients in EDOU. Most of respondents (73.7%) reported an admission rate within 20%, primarily in cardiology, in the case of an established or suspected cardiac etiology of syncope. In most centers, the referral to the general practitioner is the priority path at discharge from ED. Nearly 50% of participants rated syncope management in their own center as sub-optimal. To optimize it, 98% of them believe that is appropriate to implement a standardized approach, with and a large majority focusing on increasing diagnostic yield and safety; other priorities include application of guidelines, implementation of care pathways, enhancement of the role of EDOU, and direct path to the SU. This study highlights that the management of syncope patients in our country requires a further improvement, especially through standardization of pathways and adoption of innovative organizational solutions. Admissions appear to be lower than reported in the literature but this finding must be confirmed by a multicentric study based on direct collection of data.

Availability of emergency contraception: a survey of hospital emergency department gynaecologists and emergency physicians in Piedmont, Italy.

OBJECTIVES: To compare the knowledge and the willingness of emergency physicians and gynaecologists caring for women in Italian emergency departments (EDs) to prescribe levonorgestrel-only emergency contraceptive pills (LNG-EC pills). METHODS: A cross-sectional survey was conducted in 2009; anonymous postal questionnaires were mailed to the medical staff working at the 30 EDs located in Piedmont (Italy). RESULTS: Emergency physicians and gynaecologists have similar knowledge of the pharmacokinetics and pharmacodynamics of LNG-EC pills, but do not feel at ease in prescribing these and consider the prescription of LNG-EC pills an inappropriate activity for ED staff. CONCLUSIONS: In Italy, unlike in most other European countries, LNG-EC pills are still prescription drugs. Thus it may be useful to further investigate the reasons why Italian ED medical staff do not feel the prescription of LNG-EC pills should be within their remit and whether women can successfully obtain the prescription from physicians working in other services that can be accessed around the clock.

How to simplify the implementation of Syncope ESC Guidelines in the Emergency Department and get on the road to achieve "zero inappropriate admissions".

According to 2018 ESC Guidelines for syncope, the first aim in ED evaluation is to identify patients with underlying acute diseases, at higher risk of short-term adverse events; in the meantime, emergency physicians should also identify cases of hypotensive syncope elicited by non-severe concurrent conditions, as they mostly do not require hospitalization. After excluding these cases, ESC GL state that patients should be managed with initial evaluation and risk stratification, providing several tables and flow-charts to do it. To optimize ED management, we propose to combine these two phases, as in the clinical practice they occur at the same, with the following simplified paths: patients with only clinical features suggestive of reflex syncope should be discharged, with a fast-track to an outpatient Syncope Unit only in case of severe syncope; patients with orthostatic syncope could be discharged with measures to prevent recurrences or be managed in an ED Observation Unit (EDOU) in case of fluid loss or other causes of volume depletion; patients with major clinical or ECG criteria suggestive of cardiogenic syncope should be admitted, for diagnostic or therapeutic purposes; patients with undetermined syncope or minor clinical or ECG criteria suggestive of cardiogenic syncope should be managed in an EDOU. ESC GL give focus to this novel care pathway, but they do not provide clear details on the organizational aspects; accordingly, this document proposes resources and protocols for managing patients in EDOU, as a first part of the functional path of the outpatient Syncope Unit.

Can Alveolar-Arterial Difference and Lung Ultrasound Help the Clinical Decision Making in Patients with COVID-19?

BACKGROUND: COVID-19 is an emerging infectious disease, that is heavily challenging health systems worldwide. Admission Arterial Blood Gas (ABG) and Lung Ultrasound (LUS) can be of great help in clinical decision making, especially during the current pandemic and the consequent overcrowding of the Emergency Department (ED). The aim of the study was to demonstrate the capability of alveolar-to-arterial oxygen difference (AaDO2) in predicting the need for subsequent oxygen support and survival in patients with COVID-19 infection, especially in the presence of baseline normal PaO2/FiO2 ratio (P/F) values. METHODS: A cohort of 223 swab-confirmed COVID-19 patients underwent clinical evaluation, blood tests, ABG and LUS in the ED. LUS score was derived from 12 ultrasound lung windows. AaDO2 was derived as AaDO2 = ((FiO2) (Atmospheric pressure - H2O pressure) - (PaCO2/R)) - PaO2. Endpoints were subsequent oxygen support need and survival. RESULTS: A close relationship between AaDO2 and P/F and between AaDO2 and LUS score was observed (R2 = 0.88 and R2 = 0.67, respectively; p < 0.001 for both). In the subgroup of patients with P/F between 300 and 400, 94.7% (n = 107) had high AaDO2 values, and 51.4% (n = 55) received oxygen support, with 2 ICU admissions and 10 deaths. According to ROC analysis, AaDO2 > 39.4 had 83.6% sensitivity and 90.5% specificity (AUC 0.936; p < 0.001) in predicting subsequent oxygen support, whereas a LUS score > 6 showed 89.7% sensitivity and 75.0% specificity (AUC 0.896; p < 0.001). Kaplan-Meier curves showed different mortality in the AaDO2 subgroups (p = 0.0025). CONCLUSIONS: LUS and AaDO2 are easy and effective tools, which allow bedside risk stratification in patients with COVID-19, especially when P/F values, signs, and symptoms are not indicative of severe lung dysfunction.

Prospective multicentre systematic guideline-based management of patients referred to the Syncope Units of general hospitals.

AIMS: Although an organizational model for syncope management facilities was proposed in the 2004 guidelines of the European Society of Cardiology (ESC), its implementation in clinical practice and its effectiveness are largely unknown. METHODS AND RESULTS: This prospective study enrolled 941 consecutive patients referred to the Syncope Units of nine general hospitals from 15 March 2008 to 15 September 2008. A median of 15 patients per month were examined in each unit, but the five older units had a two-fold higher volume of activity than the four newer ones (instituted <1 year before): 23 vs. 12, P = 0.02. These figures give an estimated volume of 163 and 60 patients per 100,000 inhabitants per year, respectively. Referrals: 60% from out-of-hospital services, 11% immediate and 13% delayed referrals from the Emergency Department, and 16% hospitalized patients. A diagnosis was established on initial evaluation in 191 (21%) patients and early by means of 2.9 +/- 1.6 tests in 541 (61%) patients. A likely reflex cause was established in 67%, orthostatic hypotension in 4%, cardiac in 6% and non-syncopal in 5% of the cases. The cause of syncope remained unexplained in 159 (18%) patients, despite a mean of 3.5 +/- 1.8 tests per patient. These latter patients were older, more frequently had structural heart disease or electrocardiographic abnormalities, unpredictable onset of syncope due to the lack of prodromes, and higher OESIL and EGSIS risk scores than the other groups of patients. The mean costs of diagnostic evaluation was 209 euro per outpatient and 1073 euro per inpatient. The median cost of hospital stay was 2990 euro per patient. CONCLUSION: We documented the current practice of syncope management in specialized facilities that have adopted the management model proposed by the ESC. The results are useful for those who wish to replicate this model in other hospitals. Syncope remains unexplained during in-hospital evaluation in more complex cases at higher risk.

Discrepancy between clinical practice and standardized indications for an implantable loop recorder in patients with unexplained syncope.

AIM: An implantable loop recorder (ILR) is indicated in patients with unexplained syncope after complete conventional work-up. Data from the literature imply that, in clinical practice, the ILR is underused. The aim of the study was to verify if there is any discrepancy between the use of ILRs in clinical practice and the potential indications based on the most potentially appropriate guideline indications. METHOD AND RESULTS: We compared the prevalence of ILRs actually implanted in patients with unexplained syncope in the Syncope Unit Project (SUP) study and the potential one using the standard given by the guidelines. In the SUP study, 28 (18%) out of 159 patients with unexplained syncope received an ILR. Appropriate criteria for implantation of ILRs according to guidelines were present in 110 (69%) patients. Moreover, 7 (25%) of ILRs actually implanted did not satisfy the guideline standards. During the follow-up, 32% of patients who had received an ILR had a diagnosis compared with 5% of those who did not (P= 0.001). CONCLUSIONS: The estimated indications were four times higher than those observed. Moreover, in about one quarter of the cases, the use of ILRs proved to be potentially inappropriate according to guideline indications. Two-thirds of patients with unexplained syncope had indications potentially appropriate for ILRs.

Point-of-care testing in critical care: the clinician's point of view.

Point-of-care testing (POCT) is increasingly used in the Emergency Department (ED) by emergency physicians. They often need to have test results readily available in order to make prompt diagnosis, define risk stratification and establish early therapy or make changes to therapy. The use of POCT is important in patients who present to the ED with symptoms, such as chest pain, dyspnea or other critical medical conditions, as well as in trauma patients. The essential tests should have a turn-around time that allows state-of-the-art management of critical patients. The quality of POCT analyses can only be assured through an optimal relationship with the clinical laboratory, and all POCT activities should be discussed and agreed upon between the Clinical Laboratory and the ED.

Predictive Accuracy of Electrocardiographic Monitoring of Patients With Syncope in the Emergency Department: The SyMoNE Multicenter Study.

BACKGROUND: Arrhythmia is one of the most worrisome causes of syncope. Electrocardiographic (ECG) monitoring is crucial for the management of non-low-risk patients in the emergency department (ED). However, its diagnostic accuracy and optimal duration are unknown. We aimed to assess the diagnostic accuracy of ECG monitoring in non-low-risk patients with syncope in the ED. METHODS: This prospective multicenter observational study included adult patients presenting to the ED after syncope. Patients without an obvious etiology after ED evaluation who were classified by ED physicians as being at non-low risk of adverse events underwent ECG monitoring. We assessed sensitivity, specificity, and diagnostic yield (defined as the proportion of patients with true-positive ECG monitoring findings) of ECG monitoring in the identification of 7- and 30-day adverse and arrhythmic events according to monitoring duration. RESULTS: Of 242 patients included in the study, 29 patients had 7-day serious outcomes. Ten additional patients had serious outcomes at 30 days. The overall sensitivity, specificity, and diagnostic yield of ECG monitoring in the identification of 7-day adverse events were 0.55 (95% confidence interval [CI] = 0.36 to 0.74], 0.93 (95% CI = 0.89 to 0.96), and 0.07 (95% CI = 0.04 to 0.10), respectively. The sensitivity, specificity, and diagnostic yield of >12-hour ECG monitoring in the identification of 7-day adverse events were 0.89 (95% CI = 0.65 to 0.99), 0.78 (95% CI = 0.67 to 0.87), and 0.18 (95% CI = 0.12 to 0.28), respectively. Similar results were observed for 30-day adverse events. The median (interquartile range) ECG monitoring time was 6.5 (6 to 15) hours. ECG monitoring findings were positive in 31 patients. CONCLUSIONS: Although the overall diagnostic accuracy of ECG monitoring is fair, its sensitivity at >12 hours' duration is substantially higher. These results suggest that prolonged (>12 hours) monitoring is a safe alternative to hospital admission in the management of non-low-risk patients with syncope in the ED.

Artificial Neural Networks and risk stratification models in Emergency Departments: The policy maker's perspective.

The primary goal of Emergency Department (ED) physicians is to discriminate between individuals at low risk, who can be safely discharged, and patients at high risk, who require prompt hospitalization. The problem of correctly classifying patients is an issue involving not only clinical but also managerial aspects, since reducing the rate of admission of patients to EDs could dramatically cut costs. Nevertheless, a trade-off might arise due to the need to find a balance between economic interests and the health conditions of patients. This work considers patients in EDs after a syncope event and presents a comparative analysis between two models: a multivariate logistic regression model, as proposed by the scientific community to stratify the expected risk of severe outcomes in the short and long run, and Artificial Neural Networks (ANNs), an innovative model. The analysis highlights differences in correct classification of severe outcomes at 10 days (98.30% vs. 94.07%) and 1 year (97.67% vs. 96.40%), pointing to the superiority of Neural Networks. According to the results, there is also a significant superiority of ANNs in terms of false negatives both at 10 days (3.70% vs. 5.93%) and at 1 year (2.33% vs. 10.07%). However, considering the false positives, the adoption of ANNs would cause an increase in hospital costs, highlighting the potential trade-off which policy makers might face.

Prospective study of the clinical performance of three BACTEC media in a modern emergency department: Plus Aerobic/F, Plus Anaerobic/F, and Anaerobic Lytic/F.

The performance of 3 blood culture bottles (BACTEC Plus Aerobic/F, Plus Anaerobic/F, and Anaerobic Lytic/F) were analyzed with clinical specimens collected from 688 Emergency Department patients. A total of 270 strains belonging to 33 species were identified, with E. coli and S. aureus as the most frequently detected. Overall recovery rate (RR) of bacteria and yeast was equivalent in the Plus Aerobic/F vials (208 of 270 isolates; 77.0%) and Anaerobic Lytic/F vials (206 isolates; 76.3%) and significantly better than in the Plus Anaerobic/F vials (189 isolates; 70.0%). Median time to detection (TTD) was earliest with the Anaerobic Lytic/F vials (12.0h) compared with the Plus Aerobic/F (14.6h) and Plus Anaerobic/F vials (15.4h). Positivity rate (PR) was similar for Anaerobic Lytic/F vials (76.9%) and Plus Aerobic/F vials (76.5%), but better if compared with Plus Anaerobic/F vials (69.4%). The PR and TTD for the combination of Plus Aerobic/F with Anaerobic Lytic/F (94.5% and 12.3h, respectively) was significantly better than with Plus Aerobic/F with Plus Anaerobic/F (87.8% and 14.1h).

Pilot study on harmonization of cardiac troponin I immunoassays using patients and quality control plasma samples. On behalf of the Italian Section of the European Ligand Assay Society (ELAS) and of the Study Group on Cardiovascular Biomarkers of the Società Italiana di Biochimica Clinica (SIBioC).

BACKGROUND: The aim of this study is to evaluate whether it is possible to reduce the between-methods variability of troponin I (cTnI) immunoassays using mathematical algorithms calculated from the results of both patients' samples and quality control materials distributed in an external quality assessment (EQA) scheme. METHODS: We collected 122 heparinized plasma samples of patients admitted to the emergency department with thoracic pain or supraventricular tachyarrhythmia. Moreover, we also analyzed 20 control samples distributed in an EQA and 26 plasma pools prepared from healthy subjects and patients with myocardial infarction. We evaluated 4 different methods for cTnI assay: STAT Architect High Sensitive TnI (Abbott Diagnostics), ADVIA Centaur Troponin I Ultra (Siemens Healthcare Diagnostics), ST AIA-Pack cTnI Third Generation (Tosoh Bioscience), and Access AccuTnI+3 (Beckman Coulter Diagnostics). RESULTS: Systematic differences between cTnI methods were observed. However, correlation coefficients (R from 0.976 to 0.990) between the log-transformed cTnI values measured in all 168 samples were significantly better (p=0.0037) than those obtained considering only the 122 patients' samples. cTnI values measured in EQA and pool samples were included within the 95% prediction intervals of linear regressions calculated with those of patients' samples. After the recalibration of cTnI values based on the robust principal component analysis approach the between-methods variability decreased significantly (about 40% around the cut off values). CONCLUSIONS: Our pilot study suggests that EQA schemes for cTnI immunoassay methods, based on both quality control samples with tested commutability and robust statistical analyses, are able to evaluate between-methods variability as well as allow a reliable recalibration and harmonization of results.