The Long-COVID autonomic syndrome in hospitalized patients: A one-year prospective cohort study.

Long-COVID syndrome is characterized by fatigue, orthostatic intolerance, tachycardia, pain, memory difficulties, and brain fog, which may be associated with autonomic nervous system abnormalities. We aimed to evaluate the short and long-term course of COVID-19 autonomic symptoms and quality of life (QoL) after SARS-CoV-2 infection through a one-year follow-up combined with validated questionnaires. Additionally, we aimed to identify patients with worsening autonomic symptoms at 6 and 12 months by dividing the patient cohort into two sub-groups: the Post-COVID healed Control sub-group (total score<16.4) and the Long-COVID autonomic syndrome sub-group (total score>16.4). This prospective cohort studied 112 SARS-CoV-2 positive patients discharged from Humanitas Research Hospital between January and March 2021. Autonomic symptoms and QoL were assessed using the composite autonomic symptom scale 31 (COMPASS-31) and Short Form Health Survey (SF-36) questionnaires at various time points: before SARS-CoV-2 infection (PRE), at hospital discharge (T0), and at 1 (T1), 3 (T3), 6 (T6), and 12 (T12) months of follow-up. COMPASS-31 total score, Orthostatic Intolerance and Gastrointestinal function indices, QoL, physical functioning, pain, and fatigue scores worsened at T0 compared to PRE but progressively improved at T1 and T3, reflecting the acute phase of COVID-19. Unexpectedly, these indices worsened at T6 and T12 compared to T3. Subgroup analysis revealed that 47% of patients experienced worsening autonomic symptoms at T6 and T12, indicating Long-COVID autonomic syndrome. Early rehabilitative and pharmacological therapy is recommended for patients at the T1 and T3 stages after SARS-CoV-2 infection to minimize the risk of developing long-term autonomic syndrome.

Soluble interleukin-1 receptor type 2 plasma levels in Parkinson's disease: relationship with cardiac autonomic profile before and after peripheral mechanical somatosensory stimulation.

Introduction: Systemic inflammation promotes neurodegeneration in Parkinson's disease (PD). Interleukin-1 receptor type 2 (sIL-1R2) plasma levels increase during inflammation. Data on sIL-1R2 in PD patients and its relationship with PD cardiac autonomic profile are limited, given the possible anti-inflammatory effect of vagal activation. Previously, automated mechanical peripheral somatosensory stimulation (AMPSS) enhanced cardiac vagal modulation. Objectives were to 1) evaluate sIL-1R2 plasma concentrations in PD patients and healthy controls and 2) investigate the correlations between sIL-1R2 and cardiac autonomic indices obtained by spectrum analysis of heart rate variability before and after AMPSS. Methods: sIL-1R2 plasma levels were assessed in 48 PD patients and 50 healthy controls. Electrocardiogram and beat-by-beat arterial pressure were recorded at baseline and after 5 AMPSS sessions in 16 PD patients. Results: PD patients had higher sIL-1R2 levels than controls. In the PD subgroup, an inverse correlation between sIL-1R2 and HFnu was found. There was a negative correlation between changes induced by AMPSS on HFnu and sIL-1R2. Discussion: Higher sIL-1R2 levels in PD patients reflect the inflammatory dysregulation associated with the disease. In PD patients, higher sIL-1R2 was associated with reduced cardiovagal tone. Increased cardiovagal modulation following AMPSS was associated with lower sIL-1R2 levels in Parkinson's disease patients, suggesting inflammatory state improvement.

Multimodal deep learning for COVID-19 prognosis prediction in the emergency department: a bi-centric study.

Predicting clinical deterioration in COVID-19 patients remains a challenging task in the Emergency Department (ED). To address this aim, we developed an artificial neural network using textual (e.g. patient history) and tabular (e.g. laboratory values) data from ED electronic medical reports. The predicted outcomes were 30-day mortality and ICU admission. We included consecutive patients from Humanitas Research Hospital and San Raffaele Hospital in the Milan area between February 20 and May 5, 2020. We included 1296 COVID-19 patients. Textual predictors consisted of patient history, physical exam, and radiological reports. Tabular predictors included age, creatinine, C-reactive protein, hemoglobin, and platelet count. TensorFlow tabular-textual model performance indices were compared to those of models implementing only tabular data. For 30-day mortality, the combined model yielded slightly better performances than the tabular fastai and XGBoost models, with AUC 0.87 ± 0.02, F1 score 0.62 ± 0.10 and an MCC 0.52 ± 0.04 (p < 0.32). As for ICU admission, the combined model MCC was superior (p < 0.024) to the tabular models. Our results suggest that a combined textual and tabular model can effectively predict COVID-19 prognosis which may assist ED physicians in their decision-making process.

Autoimmunity to neuronal nicotinic acetylcholine receptors.

Nicotinic acetylcholine receptors (nAChRs) are widely expressed in many and diverse cell types, participating in various functions of cells, tissues and systems. In this review, we focus on the autoimmunity against neuronal nAChRs, the specific autoantibodies and their mechanisms of pathological action in selected autoimmune diseases. We summarize the current relevant knowledge from human diseases as well as from experimental models of autoimmune neurological disorders related to antibodies against neuronal nAChR subunits. Despite the well-studied high immunogenicity of the muscle nAChRs where autoantibodies are the main pathogen of myasthenia gravis, autoimmunity to neuronal nAChRs seems infrequent, except for the autoantibodies to the ganglionic receptor, the α3 subunit containing nAChR (α3-nAChR), which are detected and are likely pathogenic in Autoimmune Autonomic Ganglionopathy (AAG). We describe the detection, presence and function of these antibodies and especially the recent development of a cell-based assay (CBA) which, contrary to until recently available assays, is highly specific for AAG. Rare reports of autoantibodies to the other neuronal nAChR subtypes include a few cases of antibodies to α7 and/or α4ß2 nAChRs in Rasmussen encephalitis, schizophrenia, autoimmune meningoencephalomyelitis, and in some myasthenia gravis patients with concurrent CNS symptoms. Neuronal-type nAChRs are also present in several non-excitable tissues, however the presence and possible role of antibodies against them needs further verification. It is likely that the future development of more sensitive and disease-specific assays would reveal that neuronal nAChR autoantibodies are much more frequent and may explain the mechanisms of some seronegative autoimmune diseases.

Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course.

Infection with severe acute respiratory syndrome coronavirus 2 associates with diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse coronavirus disease 2019 (COVID-19) outcomes. Here we discovered that antibodies against specific chemokines were omnipresent post-COVID-19, were associated with favorable disease outcome and negatively correlated with the development of long COVID at 1 yr post-infection. Chemokine antibodies were also present in HIV-1 infection and autoimmune disorders, but they targeted different chemokines compared with COVID-19. Monoclonal antibodies derived from COVID-19 convalescents that bound to the chemokine N-loop impaired cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising chemokine antibodies may modulate the inflammatory response and thus bear therapeutic potential.

Development of the Italian version of the Consultation and Relational Empathy (CARE) measure: translation, internal reliability, and construct validity in patients undergoing rehabilitation after total hip and knee arthroplasty.

PURPOSE: To translate and cross-culturally adapt the Consultation and Relational Empathy (CARE) measure into Italian, examine its internal reliability, and construct validity in a rehabilitation setting. MATERIALS AND METHODS: The translation process consisted of two forward translations, a pre-final version, a back-translation, and a final version, in accordance with available guidelines. We administered the Italian version of the CARE measure to 101 patients hospitalised for rehabilitation after total hip or total knee arthroplasty (THA and TKA). We assessed face validity, internal reliability, and construct validity. RESULTS: Face validity was high. Patients answered all questions and the "does not apply" option was never selected. Internal reliability (Cronbach's α = 0.962) resulted in line with the original version. The exploratory factor analysis confirmed the unidimensional structure of the CARE measure with 74.82% of variance explained by the first factor. CONCLUSIONS: The Italian version of the CARE measure showed high face validity. Internal reliability and construct validity were in line with the original version in patients undergoing rehabilitation after THA and TKA.IMPLICATIONS FOR REHABILITATIONInternal reliability and construct validity of the Italian version of the CARE measure are in line with those of the original version of the CARE measure.The Italian CARE measure can be used to assess patient's perceived therapist's empathy in patients undergoing physical therapy after THA and TKA.Physiotherapists should use the CARE measure with more caution in other rehabilitative contexts.

A Hybrid Model for 30-Day Syncope Prognosis Prediction in the Emergency Department.

Syncope is a challenging problem in the emergency department (ED) as the available risk prediction tools have suboptimal predictive performances. Predictive models based on machine learning (ML) are promising tools whose application in the context of syncope remains underexplored. The aim of the present study was to develop and compare the performance of ML-based models in predicting the risk of clinically significant outcomes in patients presenting to the ED for syncope. We enrolled 266 consecutive patients (age 73, IQR 58-83; 52% males) admitted for syncope at three tertiary centers. We collected demographic and clinical information as well as the occurrence of clinically significant outcomes at a 30-day telephone follow-up. We implemented an XGBoost model based on the best-performing candidate predictors. Subsequently, we integrated the XGboost predictors with knowledge-based rules. The obtained hybrid model outperformed the XGboost model (AUC = 0.81 vs. 0.73, p < 0.001) with acceptable calibration. In conclusion, we developed an ML-based model characterized by a commendable capability to predict adverse events within 30 days post-syncope evaluation in the ED. This model relies solely on clinical data routinely collected during a patient's initial syncope evaluation, thus obviating the need for laboratory tests or syncope experienced clinical judgment.

Anti-chemokine antibodies after SARS-CoV-2 infection correlate with favorable disease course.

Infection by SARS-CoV-2 leads to diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse COVID-19 outcomes. Instead, we discovered that antibodies against specific chemokines are omnipresent after COVID-19, associated with favorable disease, and predictive of lack of long COVID symptoms at one year post infection. Anti-chemokine antibodies are present also in HIV-1 infection and autoimmune disorders, but they target different chemokines than those in COVID-19. Monoclonal antibodies derived from COVID- 19 convalescents that bind to the chemokine N-loop impair cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising anti-chemokine antibodies associated with favorable COVID-19 may be beneficial by modulating the inflammatory response and thus bear therapeutic potential. One-Sentence Summary: Naturally arising anti-chemokine antibodies associate with favorable COVID-19 and predict lack of long COVID.

Diagnostic approaches to syncope in Internal Medicine Departments and their effect on mortality.

Most data on mortality and investigational approaches to syncope comes from patients presented to emergency departments (ED). The aim of this study is to report intermediate term mortality in syncope patients admitted to Internal Medicine Departments and whether different diagnostic approaches to syncope affect mortality. Methods and results A single-center retrospective-observational study conducted at the Tel Aviv "Sourasky" Medical Center. Data was collected from electronic medical records (EMRs), from January 2010 to December 2020. We identified 24,021 patients, using ICD-9-CM codes. Only 7967 syncope patients were admitted to Internal Medicine Departments and evaluated. Logistic regression models were used to determine the effects of diagnostic testing per patient in each department on 30-day mortality and readmission rates. All-cause 30-day mortality rate was 4.1%. There was a significant difference in the number of diagnostic tests performed per patient between the different departments, without affecting 30-day mortality. The 30-day readmission rate was 11.4%, of which 4.4% were a result of syncope. Conclusion Syncope patients admitted to Internal Medicine Departments show a 30-day all-cause mortality rate of ∼4%. Despite the heterogeneity in the approach to the diagnosis of syncope, mortality is not affected. This novel information about syncope patients in large Internal Medicine Departments is further proof that the diagnosis of syncope requires a logic, personalized approach that focuses on medical history and a few tailored, diagnostic tests.

Novel Cell-Based Assay for Alpha-3 Nicotinic Receptor Antibodies Detects Antibodies Exclusively in Autoimmune Autonomic Ganglionopathy.

BACKGROUND AND OBJECTIVES: Autoantibodies against α3-subunit-containing nicotinic acetylcholine receptors (α3-nAChRs), usually measured by radioimmunoprecipitation assay (RIPA), are detected in patients with autoimmune autonomic ganglionopathy (AAG). However, low α3-nAChR antibody levels are frequently detected in other neurologic diseases with questionable significance. Our objective was to develop a method for the selective detection of the potentially pathogenic α3-nAChR antibodies, seemingly present only in patients with AAG. METHODS: The study involved sera from 55 patients from Greece, suspected for autonomic failure, and 13 patients from Italy diagnosed with autonomic failure, positive for α3-nAChR antibodies by RIPA. In addition, sera from 52 patients with Ca2+ channel or Hu antibodies and from 2,628 controls with various neuroimmune diseases were included. A sensitive live cell-based assay (CBA) with α3-nAChR-transfected cells was developed to detect antibodies against the cell-exposed α3-nAChR domain. RESULTS: Twenty-five patients were found α3-nAChR antibody positive by RIPA. Fifteen of 25 patients were also CBA positive. Of interest, all 15 CBA-positive patients had AAG, whereas all 10 CBA-negative patients had other neurologic diseases. RIPA antibody levels of the CBA-negative sera were low, although our CBA could detect dilutions of AAG sera corresponding to equally low RIPA antibody levels. No serum bound to control-transfected cells, and none of the 2,628 controls was α3-CBA positive. DISCUSSION: This study showed that in contrast to the established RIPA for α3-nAChR antibodies, which at low levels is of moderate disease specificity, our CBA seems AAG specific, while at least equally sensitive with the RIPA. This study provides Class II evidence that α3-nAChR CBA is a specific assay for AAG. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that an α3-nAChR cell-based assay is a more specific assay for AAG than the standard RIPA.

Learning Analytics Applied to Clinical Diagnostic Reasoning Using a Natural Language Processing-Based Virtual Patient Simulator: Case Study.

BACKGROUND: Virtual patient simulators (VPSs) log all users' actions, thereby enabling the creation of a multidimensional representation of students' medical knowledge. This representation can be used to create metrics providing teachers with valuable learning information. OBJECTIVE: The aim of this study is to describe the metrics we developed to analyze the clinical diagnostic reasoning of medical students, provide examples of their application, and preliminarily validate these metrics on a class of undergraduate medical students. The metrics are computed from the data obtained through a novel VPS embedding natural language processing techniques. METHODS: A total of 2 clinical case simulations (tests) were created to test our metrics. During each simulation, the students' step-by-step actions were logged into the program database for offline analysis. The students' performance was divided into seven dimensions: the identification of relevant information in the given clinical scenario, history taking, physical examination, medical test ordering, diagnostic hypothesis setting, binary analysis fulfillment, and final diagnosis setting. Sensitivity (percentage of relevant information found) and precision (percentage of correct actions performed) metrics were computed for each issue and combined into a harmonic mean (F1), thereby obtaining a single score evaluating the students' performance. The 7 metrics were further grouped to reflect the students' capability to collect and to analyze information to obtain an overall performance score. A methodological score was computed based on the discordance between the diagnostic pathway followed by students and the reference one previously defined by the teacher. In total, 25 students attending the fifth year of the School of Medicine at Humanitas University underwent test 1, which simulated a patient with dyspnea. Test 2 dealt with abdominal pain and was attended by 36 students on a different day. For validation, we assessed the Spearman rank correlation between the performance on these scores and the score obtained by each student in the hematology curricular examination. RESULTS: The mean overall scores were consistent between test 1 (mean 0.59, SD 0.05) and test 2 (mean 0.54, SD 0.12). For each student, the overall performance was achieved through a different contribution in collecting and analyzing information. Methodological scores highlighted discordances between the reference diagnostic pattern previously set by the teacher and the one pursued by the student. No significant correlation was found between the VPS scores and hematology examination scores. CONCLUSIONS: Different components of the students' diagnostic process may be disentangled and quantified by appropriate metrics applied to students' actions recorded while addressing a virtual case. Such an approach may help teachers provide students with individualized feedback aimed at filling competence drawbacks and methodological inconsistencies. There was no correlation between the hematology curricular examination score and any of the proposed scores as these scores address different aspects of students' medical knowledge.

Effects of a cool classroom microclimate on cardiac autonomic control and cognitive performances in undergraduate students.

An inverted U-shape relationship between cognitive performance and indoor temperature with best performance peaking at 21.6 °C was previously described. Little is known on classroom temperature reduction effects on cognitive performances and cardiac autonomic profile, during the cold season. Fifteen students underwent electrocardiogram recording during a lecture in two days in December when classroom temperatures were set as neutral (NEUTRAL, 20-22 °C) and cool (COOL, 16-18 °C). Cognitive performance (memory, verbal ability, reasoning, overall cognitive C-score) was assessed by Cambridge Brain Science cognitive evaluation tool. Cardiac autonomic control was evaluated via the analysis of spontaneous fluctuations of heart period, as the temporal distance between two successive R-wave peaks (RR). Spectral analysis provided the power in the high frequency (HF, 0.15-0.40 Hz) and low frequency (LF, 0.04-0.15 Hz) bands of RR variability. Sympatho-vagal interaction was assessed by LF to HF ratio (LF/HF). Symbolic analysis provided the fraction of RR patterns composed by three heart periods with no variation (0 V%) and two variations (2 V%), taken as markers of cardiac sympathetic and vagal modulations, respectively. The students' thermal comfort was assessed during NEUTRAL and COOL trials. Classroom temperatures were 21.5 ± 0.8 °C and 18.4 ± 0.4 °C during NEUTRAL and COOL. Memory, verbal ability, C-Score were greater during COOL (13.01 ± 3.43, 12.32 ± 2.58, 14.29 ± 2.90) compared to NEUTRAL (9.98 ± 2.26, p = 0.002; 8.57 ± 1.07, p = 0.001 and 10.35 ± 3.20, p = 0.001). LF/HF (2.4 ± 1.7) and 0 V% (23.2 ± 11.1%) were lower during COOL compared to NEUTRAL (3.7 ± 2.8, p = 0.042; 28.1 ± 12.2.1%, p = 0.031). During COOL, 2 V% was greater (30.5 ± 10.9%) compared to NEUTRAL (26.2 ± 11.3, p = 0.047). The students' thermal comfort was slightly reduced during COOL compared to NEUTRAL trial. During cold season, a better cognitive performance was obtained in a cooler indoor setting enabling therefore energy saving too.

Syncope Time Frames for Adverse Events after Emergency Department Presentation: An Individual Patient Data Meta-Analysis.

Background and Objectives: Knowledge of the incidence and time frames of the adverse events of patients presenting syncope at the ED is essential for developing effective management strategies. The aim of the present study was to perform a meta-analysis of the incidence and time frames of adverse events of syncope patients. Materials and Methods: We combined individual patients' data from prospective observational studies including adult patients who presented syncope at the ED. We assessed the pooled rate of adverse events at 24 h, 72 h, 7-10 days, 1 month and 1 year after ED evaluation. Results: We included nine studies that enrolled 12,269 patients. The mean age varied between 53 and 73 years, with 42% to 57% females. The pooled rate of adverse events was 5.1% (95% CI 3.4% to 7.7%) at 24 h, 7.0% (95% CI 4.9% to 9.9%) at 72 h, 8.4% (95% CI 6.2% to 11.3%) at 7-10 days, 10.3% (95% CI 7.8% to 13.3%) at 1 month and 21.3% (95% CI 15.8% to 28.0%) at 1 year. The pooled death rate was 0.2% (95% CI 0.1% to 0.5%) at 24 h, 0.3% (95% CI 0.1% to 0.7%) at 72 h, 0.5% (95% CI 0.3% to 0.9%) at 7-10 days, 1% (95% CI 0.6% to 1.7%) at 1 month and 5.9% (95% CI 4.5% to 7.7%) at 1 year. The most common adverse event was arrhythmia, for which its rate was 3.1% (95% CI 2.0% to 4.9%) at 24 h, 4.8% (95% CI 3.5% to 6.7%) at 72 h, 5.8% (95% CI 4.2% to 7.9%) at 7-10 days, 6.9% (95% CI 5.3% to 9.1%) at 1 month and 9.9% (95% CI 5.5% to 17) at 1 year. Ventricular arrhythmia was rare. Conclusions: The risk of death or life-threatening adverse event is rare in patients presenting syncope at the ED. The most common adverse events are brady and supraventricular arrhythmias, which occur during the first 3 days. Prolonged ECG monitoring in the ED in a short stay unit with ECG monitoring facilities may, therefore, be beneficial.

Transdermal auricular vagus stimulation for the treatment of postural tachycardia syndrome.

Postural Tachycardia Syndrome (POTS) is a chronic disorder characterized by symptoms of orthostatic intolerance such as fatigue, lightheadedness, dizziness, palpitations, dyspnea, chest discomfort and remarkable tachycardia upon standing. Non-invasive transdermal vagal stimulators have been applied for the treatment of epilepsy, anxiety, depression, headache, and chronic pain syndromes. Anti-inflammatory and immunomodulating effects after transdermal vagal stimulation raised interest for applications in other diseases. Patients with sympathetic overactivity, reduced cardiac vagal drive and presence of systemic inflammation like POTS may benefit from tVNS. This article will address crucial methodological aspects of tVNS and provide preliminary results of its acute and chronic use in POTS, with regards to its potential effectiveness on autonomic symptoms reduction and heart rate modulation.

Serum ANCA and Overall Mortality: A 10-Year Retrospective Cohort Study on 1,024 Italian Subjects.

Background: Antineutrophil cytoplasmic antibodies (ANCA) are primarily involved in the pathogenesis of ANCA-associated vasculitides (AAV). However, ANCA may also be present in healthy subjects and in patients with autoimmune disorders different from AAV. We hypothesized that serum ANCA are associated with a worse prognosis in disorders other than AAV. Objective: We investigated the association between the overall survival and the presence of serum ANCA in 1,024 Italian subjects with various testing indications in a 10-year interval. Methods: In this retrospective cohort study, a population of 6,285 patients (many of whom were subsequently excluded due to our criteria) who tested for ANCA at a single center in 10 years was considered, and life status and comorbidities of subjects were collected. We compared the overall survival of ANCA-positive and ANCA-negative patients by means of Kaplan-Meier curves, while a multivariable adjusted Cox regression was used to evaluate the association between the ANCA status and the outcome (death) in terms of hazard ratios (HR) with 95% confidence intervals (CI). Results: The positivity of perinuclear ANCA (pANCA) increased significantly mortality (HR, 1.60; 95% CI, 1.10-2.32), while cytoplasmic ANCA (cANCA) positivity failed to show a significant association (HR, 1.43; 95% CI, 0.77-2.68). The increased mortality rate was observed for both pANCA and cANCA in patients suffering from rheumatic disorders. No association was found between mortality and anti-MPO (HR, 0.63; 95% CI, 0.20-2.00) or anti-PR3 (HR, 0.98; 95% CI, 0.24-3.96) after adjusting for confounders. Conclusions: Serum pANCA and cANCA are independent negative prognostic factors in patients with concurrent autoimmune diseases.

Impact of implementing a Choosing Wisely educational intervention into clinical practice: The CW-SIMI study (a multicenter-controlled study).

OBJECTIVES: To evaluate the impact of an educational intervention based on the Italian Society of Internal Medicine Choosing Wisely (CW-SIMI) recommendations. DESIGN: Multicenter, interventional, controlled study. SETTING: Twenty-three acute-care hospital wards in Italy. PARTICIPANTS: 303 Physicians working in internal medicine wards. INTERVENTION: An online educational course. MAIN OUTCOMES: The rate of proton pump inhibitor (PPI) prescriptions, the number of days of central venous catheter (CVC) usage, and the duration of intravenous (IV) antibiotic prescriptions evaluated at one month (T1) and at six months (T2) after course completion. Patients admitted and discharged during a 30-day period before the educational intervention (T0, one year before T2) were considered the comparison group. RESULTS: A total of 232 physicians completed the course, while 71 did not attend the course. Data from 608, 662, and 555 patients were analyzed at T0, T1, and T2, respectively. The rate of PPI prescriptions declined at one month (RR: 0.67, 95% CI: 0.52-0.87, p = 0.0005) and at six months (RR: 0.62, 95% CI: 0.46-0.84, p = 0.003), and the number of days of CVC usage was reduced at six months (9.13 days at T0 vs. 5.52 days at T2, p = 0.007). The duration of IV antibiotic prescriptions displayed a decreasing trend (7.94 days at T0 vs. 7.42 days at T2, p = 0.081). CONCLUSIONS: A simple online educational intervention based on the CW-SIMI recommendations was associated with a clinically relevant reduction in the usage of PPIs and CVCs. Further studies are needed to confirm these findings and a possible benefit on patients' outcomes.

Correction: Personalized risk stratification through attribute matching for clinical decision making in clinical conditions with aspecific symptoms: The example of syncope.

[This corrects the article DOI: 10.1371/journal.pone.0228725.].

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.