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BackgroundThe 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.MethodsUsing 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.ResultsFrom 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.ConclusionThis 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.

Clinical deterioration of COVID-19 patients is still a challenging event to predict in the emergency department (ED). The present study developed an artificial neural network using textual and tabular data from ED electronic medical reports. Predicted outcomes were 30-day mortality and ICU admission. Consecutive patients between February 20 and May 5, 2020, from Humanitas Research Hospital and San Raffaele Hospital, in the Milan area, were included. COVID-19 patients were 1296. Textual predictors were patient history, physical exam, and radiological reports. Tabular predictors were age, creatinine, C-reactive protein, hemoglobin, and platelet count. Tabular-textual model performance indices were compared to a model implementing only tabular data. For 30-day mortality, the combined model yielded slightly better performances than the tabular model, with AUC 0.84 ± 0.02, F-1 score 0.56 ± 0.04 and an MCC 0.44 ± 0.04. Tabular model performance was: AUC 0.84 ± 0.02, F-1 score 0.55 ± 0.03 and MCC 0.43 ± 0.04. As for ICU admission, the combined model was not superior to the tabular one. The present data points to the effectiveness of a textual and tabular model for COVID-19 prognosis prediction. Also, it may support the ED physician in their decision-making process.

Eventos adversos; Arritmia; Resultados Adverse events; Arrhythmia; Outcomes Esdeveniments adversos; Arítmia; Resultats 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. This research received no external funding.

This prospective cohort enrolled all patients above 16 years of age presenting to the in the emergency department (ED) for a reported syncope was designed to test the accuracy of a point-of-care ultrasound (POCUS) integrated approach in risk stratification. The emergency physician responsible for the patient care was asked to classify the syncope risk after the initial clinical assessment and after performing POCUS evaluation. All risk group definitions were based on the 2018 European Society of Cardiology guidelines. Thirty days after the index event, all participants were followed up to assess the frequency of short-term serious outcomes as defined in the San Francisco Syncope Rule (SFSR) cohorts. We estimated the accuracy of clinical and POCUS-integrated evaluation in predicting SFSR outcomes. Between February 2016 and January 2018, 196 patients were enrolled [109 women (55.6%)]. Median age was 64 years (interquartile range 31 years). After a follow-up of 30 days, 19 patients experienced 20 SFSR outcomes. Positive and negative likelihood ratios were 1.73 (95% CI 0.87-3.44) and 0.84 (95% CI 0.62-1.12) for the clinical evaluation, and 5.93 (95% CI 2.83-12.5) and 0.63 (95% CI 0.45-0.9) for the POCUS-integrated evaluation. The POCUS-integrated approach would reduce the diagnostic error of the clinical evaluation by 4.5 cases/100 patients. This cohort study suggested that the integration of the clinical assessment with POCUS results in patients presenting to the ED for non-high-risk syncope may increase the accuracy of predicting the risk of SFSR outcomes and the usefulness of the clinical assessment alone.

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.

Background Shortage of human resources, increasing educational costs, and the need to keep social distances in response to the COVID-19 worldwide outbreak have prompted the necessity of clinical training methods designed for distance learning. Virtual patient simulators (VPSs) may partially meet these needs. Natural language processing (NLP) and intelligent tutoring systems (ITSs) may further enhance the educational impact of these simulators. Objective The goal of this study was to develop a VPS for clinical diagnostic reasoning that integrates interaction in natural language and an ITS. We also aimed to provide preliminary results of a short-term learning test administered on undergraduate students after use of the simulator. Methods We trained a Siamese long short-term memory network for anamnesis and NLP algorithms combined with Systematized Nomenclature of Medicine (SNOMED) ontology for diagnostic hypothesis generation. The ITS was structured on the concepts of knowledge, assessment, and learner models. To assess short-term learning changes, 15 undergraduate medical students underwent two identical tests, composed of multiple-choice questions, before and after performing a simulation by the virtual simulator. The test was made up of 22 questions; 11 of these were core questions that were specifically designed to evaluate clinical knowledge related to the simulated case. Results We developed a VPS called Hepius that allows students to gather clinical information from the patient’s medical history, physical exam, and investigations and allows them to formulate a differential diagnosis by using natural language. Hepius is also an ITS that provides real-time step-by-step feedback to the student and suggests specific topics the student has to review to fill in potential knowledge gaps. Results from the short-term learning test showed an increase in both mean test score (P Conclusions By combining ITS and NLP technologies, Hepius may provide medical undergraduate students with a learning tool for training them in diagnostic reasoning. This may be particularly useful in a setting where students have restricted access to clinical wards, as is happening during the COVID-19 pandemic in many countries worldwide.

In recent years, machine learning (ML) has been promisingly applied in many fields of clinical medicine, both for diagnosis and prognosis prediction. Aims of this narrative review were to summarize the basic concepts of ML applied to clinical medicine and explore its main applications in the emergency department (ED) setting, with a particular focus on syncope management. Through an extensive literature search in PubMed and Embase, we found increasing evidence suggesting that the use of ML algorithms can improve ED triage, diagnosis, and risk stratification of many diseases. However, the lacks of external validation and reliable diagnostic standards currently limit their implementation in clinical practice. Syncope represents a challenging problem for the emergency physician both because its diagnosis is not supported by specific tests and the available prognostic tools proved to be inefficient. ML algorithms have the potential to overcome these limitations and, in the future, they could support the clinician in managing syncope patients more efficiently. However, at present only few studies have addressed this issue, albeit with encouraging results.

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. CLINICALTRIAL

BACKGROUND Shortage of human resources, increasing educational costs, and the need to keep social distances in response to the COVID-19 worldwide outbreak have prompted the necessity of clinical training methods designed for distance learning. Virtual patient simulators (VPSs) may partially meet these needs. Natural language processing (NLP) and intelligent tutoring systems (ITSs) may further enhance the educational impact of these simulators. OBJECTIVE The goal of this study was to develop a VPS for clinical diagnostic reasoning that integrates interaction in natural language and an ITS. We also aimed to provide preliminary results of a short-term learning test administered on undergraduate students after use of the simulator. METHODS We trained a Siamese long short-term memory network for anamnesis and NLP algorithms combined with Systematized Nomenclature of Medicine (SNOMED) ontology for diagnostic hypothesis generation. The ITS was structured on the concepts of knowledge, assessment, and learner models. To assess short-term learning changes, 15 undergraduate medical students underwent two identical tests, composed of multiple-choice questions, before and after performing a simulation by the virtual simulator. The test was made up of 22 questions; 11 of these were core questions that were specifically designed to evaluate clinical knowledge related to the simulated case. RESULTS We developed a VPS called Hepius that allows students to gather clinical information from the patient’s medical history, physical exam, and investigations and allows them to formulate a differential diagnosis by using natural language. Hepius is also an ITS that provides real-time step-by-step feedback to the student and suggests specific topics the student has to review to fill in potential knowledge gaps. Results from the short-term learning test showed an increase in both mean test score (PP CONCLUSIONS By combining ITS and NLP technologies, Hepius may provide medical undergraduate students with a learning tool for training them in diagnostic reasoning. This may be particularly useful in a setting where students have restricted access to clinical wards, as is happening during the COVID-19 pandemic in many countries worldwide.

Postural orthostatic tachycardia syndrome (POTS) is a multifactorial condition capable of chronically reducing the quality of life and the work ability of patients. The study aim was to assess the burden of autonomic symptoms in a cohort of POTS patients over 2 years. Patients&rsquo, clinical profiles were assessed by the 31-item Composite Autonomic Symptom Score questionnaire (COMPASS 31) and a visual analog scale (VAS). One-way ANOVA for repeated measures followed by Dunnett&rsquo, s post-hoc test were used to compare symptoms at baseline and at 1 and 2 years. Out of 42 enrolled patients, 25 had a 1-year follow-up and 12 had a 2-year follow-up. At baseline, the reported burden of autonomic symptoms was high (overall COMPASS 31 = 49.9 &plusmn, 14.3 /100). Main complaints were related to orthostatic intolerance according to both COMPASS 31 and VAS. Fourteen patients were rendered inactive because of symptoms. At 1-year follow-up, a statistically significant improvement in pupillomotor function and overall score was detected by the COMPASS 31. These findings were confirmed at 2 years, together with a significant reduction in quality of life impairment, assessed by VAS. However, these improvements did not change patients&rsquo, occupational status. Awareness of POTS diagnosis, patient monitoring, and tailored therapies can help to improve patients&rsquo, condition.

The effect of classroom temperature reduction on cognitive performance and cardiac autonomic control were assessed in 12 healthy undergraduate students during a 2-hour lasting lecture. In all subjects ECG was continuously recorded by a portable device when classroom temperature was “neutral” $(22.4\pm 0.1^{\circ}\mathrm{C}$ , Day1) and “cool” $(18.4^{\circ}\mathrm{C}\pm 0.3^{\circ}\mathrm{C}$ , Day2). Symbolic analysis of RR variability provided the percentage of three heart period sequences with no significant change in RR interval (0V%) and with two significant variations (2UV%), reflecting cardiac sympathetic and vagal modulation, respectively. Students' cognitive performance was assessed at the end of each lecture by the Cambridge Brain Sciences cognitive evaluation tool. In Day2 the 0V% was greater and 2UV% was lower compared to Day1. Cognitive performance rated better in Day2 compared to Day1. Students' cognitive performance was improved and their cardiac sympathetic modulation was enhanced when the lecture was performed in a cooler environment.

The capability of hypnosis to act on the Autonomic Nervous System under a controlled breath condition (12 breaths/min) was assessed in 11 healthy volunteers. Subjects were split into high and low susceptibility to hypnosis groups, using the Stanford hypnotic susceptibility scale form $\mathrm{C}$ (SHSS). Autoregressive power spectrum analysis of RR interval and SAP variabilities provided the markers of cardiac sympatho-vagal interaction (LF/HF) and vascular sympathetic vasomotor control $(\mathrm{LF}_{\mathrm{SAP}})$ . Under controlled respiration, no significant changes in LF/HF ratio were observed between the two groups. Hypnosis induced a significant increase of $\mathrm{LF}_{\mathrm{SAP}}$ in high susceptible subjects. These preliminary results highlight how the state of hypnotic trance acts directly on the cardiovascular autonomic profile by increasing the sympathetic vascular activity only in high susceptible subjects. These effects become evident when the role of potential changes in respiration rate are excluded by the controlled breathing condition.

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.

Syncope is the common clinical manifestation of different diseases, and this makes it difficult to define what outcomes should be considered in prognostic studies. The aim of this study is to critically analyze the outcomes considered in syncope studies through systematic review and expert consensus. We performed a systematic review of the literature to identify prospective studies enrolling consecutive patients presenting to the Emergency Department with syncope, with data on the characteristics and incidence of short-term outcomes. Then, the strengths and weaknesses of each outcome were discussed by international syncope experts to provide practical advice to improve future selection and assessment. 31 studies met our inclusion criteria. There is a high heterogeneity in both outcome choice and incidence between the included studies. The most commonly considered 7-day outcomes are mortality, dysrhythmias, myocardial infarction, stroke, and rehospitalisation. The most commonly considered 30-day outcomes are mortality, haemorrhage requiring blood transfusion, dysrhythmias, myocardial infarction, pacemaker or implantable defibrillator implantation, stroke, pulmonary embolism, and syncope relapse. We present a critical analysis of the pros and cons of the commonly considered outcomes, and provide possible solutions to improve their choice in ED syncope studies. We also support global initiatives to promote the standardization of patient management and data collection.

Background Guidelines recommend that implantable loop recorders (ILRs) are used in the evaluation of people with recurrent unexplained syncope in the absence of high-risk criteria, and in high-risk patients after a negative evaluation. The aim of this systematic review was to analyze the diagnostic yield of ILRs in these patients. Methods We performed a systematic search in order to retrieve studies enrolling adults undergoing ILR implantation for undetermined syncope. The primary outcome was the overall diagnostic yield, defined as the proportion of patients with syncope recurrence and an available ILR recording or an automatic detection of a significant arrhythmia. Secondary outcomes were the proportions of patients with the specific etiologic diagnoses on the total of subjects and the proportion of an analyzable ECG recording during symptoms. We used a random effects model for the meta-analyses. Results Forty-nine studies, enrolling 4381 subjects, were included. The overall diagnostic yield was 43.9% (95% CI=40.2%, 47.6%; I 2 =79.8%). The proportions of subjects finally diagnosed with arrhythmic syncope, ventricular arrhythmias, supraventricular arrhythmias and bradyarrhythmias were 26.5%, 2.7%, 4.9% and 18.2%, respectively. The proportion of an analyzable ECG recording during symptoms was 89.5% (95% CI=86.1%, 92.1%; 1236 subjects; 36 studies; I 2 =44.9%). Median time to diagnosis was 134days. Heterogeneity is an important limitation to be acknowledged. Conclusions About a half of unexplained syncope subjects implanted with an ILR were diagnosed, and around 50% of them had an arrhythmia. Life-threatening arrhythmias as well as ILR complications and death due to arrhythmic events were very rare.

Psychogenic Pseudosyncope (PPS) is the appearance of Transient Loss of Consciousness (TLOC) in which movements are absent, but there are no hemodynamic and electroencephalographic modifications as are induced by gravitational challenges which characterize syncope and true loss of consciousness. For younger and adult populations, a detailed history is crucial for the diagnosis. Clinical clues that should raise the suspicion for PPS include prolonged duration of the LOC, eye closure during the episode, unusual triggers, no recognizable prodromes and the high frequency of attacks. The presence of an established diagnosis of syncope should not deter from the concomitant diagnosis of PPS. The gold standard for a proper diagnosis of PPS is the documentation by a tilt test of normal hemodynamic and electroencephalographic parameters, when recorded during an attack. Treatment of PPS, based on the clear and empathetic communication of the diagnosis, can lead to an immediate reduction of attack frequency and lower the need to call on emergency services. Pharmacological treatment of associated psychiatric disorders and psychological interventions may be beneficial in patients with PPS. Cognitive-behavioural therapy holds the most reliable evidence of efficacy. In the present review, we aimed to address PPS with historical aspects, main clinical features and diagnostic tests, current diagnostic classification, underlying neurobiological abnormalities, management and therapy.

Background: Enrollment of large cohorts of syncope patients from administrative data is crucial for proper risk stratification but is limited by the enormous amount of time required for manual revision of medical records. Aim: To develop a Natural Language Processing (NLP) algorithm to automatically identify syncope from Emergency Department (ED) electronic medical records (EMRs). Methods: De-identified EMRs of all consecutive patients evaluated at Humanitas Research Hospital ED from 1 December 2013 to 31 March 2014 and from 1 December 2015 to 31 March 2016 were manually annotated to identify syncope. Records were combined in a single dataset and classified. The performance of combined multiple NLP feature selectors and classifiers was tested. Primary Outcomes: NLP algorithms&rsquo, accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F3 score. Results: 15,098 and 15,222 records from 2013 and 2015 datasets were analyzed. Syncope was present in 571 records. Normalized Gini Index feature selector combined with Support Vector Machines classifier obtained the best F3 value (84.0%), with 92.2% sensitivity and 47.4% positive predictive value. A 96% analysis time reduction was computed, compared with EMRs manual review. Conclusions: This artificial intelligence algorithm enabled the automatic identification of a large population of syncope patients using EMRs.

We hypothesized that sympathetic baroreflex mediated uncoupling between neural sympathetic discharge pattern and arterial pressure (AP) fluctuations at 0.1 Hz during baroreceptor unloading might promote orthostatic pre-syncope. Ten volunteers (32 &plusmn, 6 years) underwent electrocardiogram, beat-to-beat AP, respiratory activity and muscle sympathetic nerve activity (MSNA) recordings while supine (REST) and during 80&deg, head-up tilt (HUT) followed by &minus, 10 mmHg stepwise increase of lower body negative pressure until pre-syncope. Cardiac and sympathetic baroreflex sensitivity were quantified. Spectrum analysis of systolic and diastolic AP (SAP and DAP) and calibrated MSNA (cMSNA) variability assessed the low frequency fluctuations (LF, ~0.1 Hz) of SAP, DAP and cMSNA variability. The squared coherence function (K2) quantified the coupling between cMSNA and DAP in the LF band. Analyses were performed while supine, during asymptomatic HUT (T1) and at pre-syncope onset (T2). During T2 we found that: (1) sympathetic baroreceptor modulation was virtually abolished compared to T1, (2) a progressive decrease in AP was accompanied by a persistent but chaotic sympathetic firing, (3) coupling between cMSNA and AP series at 0.1 Hz was reduced compared to T1. A negligible sympathetic baroreceptor modulation during pre-syncope might disrupt sympathetic discharge pattern impairing the capability of vessels to constrict and promote pre-syncope.

The aims of this study were (1) to identify research publications studying noninvasive electrocardiogram (ECG) monitoring devices, (2) to define and categorize current technology in noninvasive ECG recording, and (3) to discuss desirable noninvasive recording features for personalized syncope evaluation to guide technological advancement and future studies. We performed a systematic review of the literature that assessed noninvasive ECG-monitoring devices, regardless of the reason for monitoring. We performed an Internet search and corresponded with syncope experts and companies to help identify further eligible products. We extracted information about included studies and device features. We found 173 relevant papers. The main reasons for ECG monitoring were atrial fibrillation (n = 45), coronary artery disease (n = 10), syncope (n = 8), palpitations (n = 8), other cardiac diseases (n = 67), and technological aspects of monitoring (n = 35). We identified 198 devices: 5 hospital telemetry devices, 12 patches, 46 event recorders, 70 Holter monitors, 23 external loop recorders, 20 mobile cardiac outpatient telemetries, and 22 multifunctional devices. The features of each device were very heterogeneous. There are a large number of ECG-monitoring devices with different features available in the market. Our findings may help clinicians select the appropriate device for their patients. Since there are only a few published articles analyzing their usefulness in syncope patients, further research might improve their use in this clinical setting.

Postural orthostatic tachycardia syndrome (POTS) negatively impacts quality of life. The excessive increase in cardiac sympathetic modulation during standing, which characterizes POTS patients, leads to many symptoms and signs of orthostatic intolerance. Little is known about the consequences of the disease on work performance and its relationship with individual autonomic profiles. Twenty-two POTS patients regularly engaged in working activity (20 females, age 36 &plusmn, 12 years) and 18 gender- and age-matched controls underwent a clinical evaluation and filled out the Work Ability Index (WAI) questionnaire. POTS patients completed the Composite Autonomic Symptom Score (COMPASS31) questionnaire, underwent continuous electrocardiogram, blood pressure and respiratory activity recordings while supine and during a 75&deg, head-up tilt (HUT). A power spectrum analysis provided the index of cardiac sympatho-vagal balance (LF/HF). WAI scores were significantly reduced in POTS patients (29.84 &plusmn, 1.40) compared to controls (45.63 &plusmn, 0.53, p &lt, 0.01). A significant inverse correlation was found between individual WAI and COMPASS31 scores (r = &minus, 0.46, p = 0.03), HUT increase in heart rate (r = &minus, 0.57, p = 0.01) and LF/HF (r = &minus, 0.55, p = 0.01). In POTS patients, the WAI scores were inversely correlated to the intensity of autonomic symptoms and to the excessive cardiac sympathetic activation induced by the gravitational stimulus.

Objective The current study aimed to assess the effects of five cycles of automated mechanical somatosensory stimulation (AMSS) of the fore-feet on blood pressure (BP) and cardiovascular autonomic control in Parkinson's Disease patients. Methods Out of 23 patients, 16 underwent an AMSS session every 72 h, for a total of five sessions per patient. Electrocardiogram, noninvasive beat-to-beat blood pressure and respiratory activity were recorded for 20 min in supine position at baseline and after the AMSS sessions. Main outcomes were the changes in SBP and DBP, in the spectral indices of cardiac sympathetic (LFRRn.u.) and vagal (HFRR) modulatory activities, cardiac sympathovagal relationship (LF/HF), vascular sympathetic modulation (LFSAP) and arterial baroreflex sensitivity (sequence technique). Symbolic analysis of heart rate variability provided additional indices of cardiac sympathetic (0V%) and vagal (2UV%) modulation to the sinoatrial node. Results After five AMSS trials a reduction in SBP (baseline: 131.2 ± 15.5 mmHg; post-AMSS: 122.4 ± 16.2 mmHg; P = 0.0004) and DBP (baseline: 73.2 ± 6.1 mmHg; post-AMSS: 68.9 ± 6.2 mmHg; P = 0.008) was observed. Post-AMSS, spectral and symbolic indices of cardiovascular sympathetic control decreased and arterial baroreflex sensitivity increased (baseline: 5.7 ± 1.3 ms/mmHg; post-AMSS: 11.27 ± 2.7 ms/mmHg). Conclusion AMSS sessions were effective in reducing BP, increasing baroreflex sensitivity and decreasing cardiovascular sympathetic modulation in Parkinson's disease patients. AMSS might be useful to control supine hypertension in Parkinson's disease.

Regular exercise is recommended to improve the cardiovascular risk profile. However, there is growing evidence that extreme volumes and intensity of long-term exertion may increase the risk of acute cardiac events. The aim of this study is to investigate the after-effects of regular, strenuous physical training on the cardiovascular neural regulation in a group of amateur triathletes compared to age-matched sedentary controls. We enrolled 11 non-elite triathletes (4 women, age 24±4 years), who had refrained from exercise for 72 hours, and 11 age-matched healthy non-athletes (3 women, age 25±2 years). Comprehensive echocardiographic and cardiopulmonary exercise tests were performed at baseline. Electrocardiogram, non-invasive blood pressure, respiratory activity, and muscle sympathetic nerve activity (MSNA) were continuously recorded in a supine position (REST) and during an incremental 15° step-wise head-up tilt test up to 75° (TILT). Blood samples were collected for determination of stress mediators. Autoregressive spectral analysis provided the indices of the cardiac sympathetic (LFRR) and vagal (HFRR) activity, the vascular sympathetic control (LFSAP), and the cardiac sympatho-vagal modulation (LF/HF). Compared to controls, triathletes were characterized by greater LFRR, LF/HF ratio, LFSAP, MSNA, and lower HFRR at REST and during TILT, i.e. greater overall cardiovascular sympathetic modulation together with lower cardiac vagal activity. Cortisol and adrenocorticotropic hormone concentrations were also higher in triathletes. In conclusion, triathletes were characterized by signs of sustained cardiovascular sympathetic overactivity. This might represent a risk factor for future cardiovascular events, given the known association between chronic excessive sympathetic activity and increased cardiovascular risk.

Syncope in a worker undertaking risky tasks may result in fatalities for the individual or for third parties. We aimed at assessing the rate of syncope recurrence and the risk factors underlying the likelihood of syncope relapse in a working-age population. A prospective cohort of all patients aged 18&ndash, 65 years consecutively admitted to the Emergency Department for syncope was enrolled. Risk of syncope relapse was assessed at a six-month, 1-year, and 5-year follow-up. Predictors of syncope recurrence have been evaluated at six months and 1 year from the syncope index by a multivariable logistic regression analysis. 348 patients were enrolled. Risk of syncope relapse was 9.2% at 6 months, 11.8% at 1 year, and 23.4% at 5 years. At 6-month follow-up, predictor of syncope recurrence was &ge, 3 prior lifetime syncope episodes. At 1-year, &ge, 3 prior lifetime syncope episodes, diabetes mellitus, and anaemia were risk factors for syncope relapse. There was an exceeding risk of recurrence in the first 6 months and a reduced risk of 3.5% per year after the first year. Anaemia, diabetes mellitus, and prior lifetime syncope burden are of importance when giving advice about the resumption of &ldquo, high risk&rdquo, jobs following a syncope episode.

Rotational shift work is associated with sleep disturbances, increased risk of cardiovascular and psychological disorders, and may negatively impact work&ndash, life balance. The direction of shift rotation (Clockwise, CW or counterclockwise, CCW) and its role in these disorders are poorly understood. The aim of the study was to investigate the effect of the shift schedule direction on sleep quantity and quality, alertness and work performance, and on work&ndash, life balance on hospital nurses. One-hundred female nurses, working a continuous rapid shift schedule in hospitals in the north of Italy, participated in this cross-sectional study. Fifty worked on CW rotation schedule (Morning: 6 a.m.&ndash, 2 p.m., Afternoon: 2 p.m.&ndash, 10 p.m., Night: 10 p.m.&ndash, 6 a.m., 2 rest days) and fifty on CCW rotation (Afternoon, Morning, Morning, Night, 3 rest days). Data were collected by ad hoc questionnaire and daily diary. During the shift cycle CW nurses slept longer (7.40 &plusmn, 2.24 h) than CCW (6.09 &plusmn, 1.73, p &lt, 0.001). CW nurses reported less frequently than CCW awakening during sleep (40% vs. 80%, 0.001), attention disturbance during work (20% vs. 64%, 0.001), and interference with social and family life (60% vs. 96% and 20% vs. 70%, respectively, 0.001). CCW rotating shift schedule seems to be characterized by higher sleep disturbances and a worse work&ndash, life balance.

BACKGROUND Constitutional hypotension (CHT) is defined as a SBP below 105 mmHg. As autonomic-related symptoms are frequently reported in CHT, these symptoms suggest that the cardiovascular autonomic control is perturbed in individuals with CHT. METHODS We investigated the autonomic cardiovascular control of 15 women with CHT and 12 women with NBP (SBP >110 mmHg). We monitored BP and ECG for autonomic function test. Supine and head up tilt (HUT) spectral analysis of RR interval and BP variability, baroreflex sensitivity and plasma levels of plasma renin activity and aldosterone were determined. M-mode echocardiogram was used to determine the left ventricle mass. RESULTS SBP and DBP were lower in CHT (97 ± 1.5 and 54 ± 1.5 mmHg) than in NBP (126 ± 3 and 70 ± 4 mmHg, P

Introduction Rapidly rotating shiftwork schedule, is common in hospital nurses as it provides continuity to the patients’ care. It has been suggested that shift rotation in clockwise (CW) direction produces less disruption of circadian rhythms than counterclockwise (CCW) rotation. Little is known about the effects of different direction of shift rotation on work-life balance, particularly in women characterised by additional commitments and responsibilities in the home and outside of work. Aim To evaluate if CW and CCW shift rotation differently impacts on family and social relationships in female nurses. Methods One hundred healthy hospital nurses (F, 20–50 years) were enrolled. Fifty of them worked in CW (Morning, M; Afternoon, A; Night, N; two rest days) and 50 in CCW (A, M, M, N, three rest days) shift rotation direction. A daily diary filled out by the nurses at the end of each work-shift provided information concerning family and social relationships during a typical working week. Habits on coffee, smoke, time of meal assumption and home management during working days were also collected. Result Nurses working on CCW shift rotation reported more frequently difficulties in keeping adequate family and social relationships compared to nurses working on CW one (96% vs 73%, p=0.002). No differences were reported in coffee (3–4 cups/day), smoking (61%) habits and time of meals assumption (irregular in about 33% of nurses) during working days in the two groups. No differences were reported in the time spent in home management by the two groups. Discussion CCW shift rotation seemed to disrupt quality of family and social relationships of nurses more than CW one. The fact that CCW shift rotation is associated to higher sleep disturbances and more fatigue in the free-time might partially explain these results. These aspects should be taken into account in shift-work schedule organisation, particularly in women.

The optimal emergency department (ED) evaluation of syncope is uncertain. Research reports from multiple countries suggest extensive practice variation, high costs, and questionable benefit associated with current approaches.1–5 Moreover, only a few of the recommendations from international syncope guidelines deal with ED management.6–8 For example, the European Society of Cardiology guidelines, which are the most inclusive syncope guidelines, do not address the ED management. This could be due to limited evidence on how to stratify the risk and decide on disposition of these patients in the ED.1,9 We organized a multi-specialty workshop of North American and European syncope experts on 26–27 September 2013 in Gargnano, Italy, with the aim of obtaining a modified Delphi consensus on the best way to manage ED syncope patients. As already described,10 we followed a four-step conceptual model for the ED decision-making in syncope: (i) Is it syncope? (ii) Is there a serious underlying condition identified in the ED? (iii) If the cause is uncertain, what is the risk of a serious outcome? (iv) For a given risk profile, how can these patients be best managed in the ED and what evaluation and restrictions are required? ( Figure 1 ) . Figure 1 Conceptual model: ED management of syncope. Expert recruitment and consensus development have been described previously.10 Details can be found in Supplementary material online, Appendix S1 . The full list of questions and answers to the first and second survey rounds as well as the degree of agreement on each item is reported in Supplementary material online, Appendix S2 . According to the ESC guidelines, syncope is defined as a …

We tested the hypothesis that altered sympathetic baroreceptor control to the vessels (svBRS) and disrupted coupling between blood pressure (BP) fluctuations and muscle sympathetic activity (MSNA) discharge pattern in the low frequency band (LF, around 0.1 Hz) precede vasovagal syncope. Seven healthy males underwent ECG, BP, respiratory, and MSNA recordings at baseline (REST) and during a 15 min 80° head-up tilt, followed by a -10 mmHg step wise increase of lower body negative pressure up to presyncope. Spectral and coherence analyses of systolic arterial pressure (SAP) and MSNA variability provided the indexes of vascular sympathetic modulation, LFSAP, and of the linear coupling between MSNA and SAP in the low frequency band (around 0.1 Hz), K(2)MSNA-SAP(LF). svBRS was assessed as the slope of the regression line between MSNA and diastolic arterial pressure (DAP). Data were analyzed at REST, during asymptomatic and presyncope periods of tilt. svBRS declined during presyncope period compared to REST and asymptomatic tilt. The presyncope period was characterized by a decrease of RR interval, LFMSNA, LFSAP, and K(2)MSNA-SAP(LF) values compared to the asymptomatic one, whereas MSNA burst rate was unchanged. The reduction of svBRS producing an altered coupling between MSNA and SAP variability at 0.1 Hz, may provoke circulatory changes leading to presyncope.

Syncope is a common condition that affects individuals of all ages and is responsible for 1–3% of all emergency department (ED) visits. Prospective studies on syncope are often limited by the exiguous number of subjects enrolled. A possible alternative approach would be to use of hospital discharge diagnoses from administrative databases to identify syncope subjects in epidemiological observational studies. We assessed the accuracy of the International Classification of Diseases, Ninth Revision (ICD-9) code 780.2 “syncope and collapse” to identify patients with syncope. Patients in two teaching hospitals in Milan, Italy with a triage assessment for ED access that was possibly related to syncope were recruited in this study. We considered the index test to be the attribution of the ICD-9 code 780.2 at ED discharge and the reference standard to be the diagnosis of syncope by the ED physician. The sensitivity, specificity, positive and negative predictive values of the ICD-9 code 780.2 to identify patients with syncope were 0.63 (95% confidence interval [CI] 0.58–0.67), 0.98 (95% CI 0.98–0.99), 0.83 (95% CI 0.79–0.87) and 0.95 (95% CI 0.94–0.95), respectively. The moderate sensitivity of ICD-9 code 780.2 should be considered when the code is used to identify patients with syncope through administrative databases.

A 63-year-old male was diagnosed with autoimmune autonomic ganglionopathy based on the finding of plasma antibodies to the nicotinic acetylcholine receptor (nAChR) of autonomic ganglia. He complained of mouth and eye dryness, dysphagia, severe constipation, erectile dysfunction, urgency, frequent urination, habitual orthostatic syncope and presyncope. A remarkable symptomatic orthostatic hypotension without changes in heart rate was present. We here describe the 3-year time course of the changes in spectral indices of cardiovascular autonomic control LF/HF and LFSAP, dysautonomia symptoms intensity and anti-nAChR antibodies following repetitive selective immunoadsorptions. During the follow-up, the reduction of anti-nAChR antibodies produced by immunoadsorption was associated with a diminished orthostatic hypotension, a restored capability to increase LF/HF, LFSAP and norepinephrine in upright position, a decline in the intensity of autonomic symptoms and an improvement of life quality. Spectral parameters LF/HF and LFSAP may represent noninvasive, low-cost biomarkers suitable for autoimmune autonomic ganglionopathy patients' clinical follow-up.

Aims Data on adverse events and death rates following syncope are heterogeneous among studies, and knowledge of syncope prognosis could help to better define the correct management of patients. Methods and results We performed a systematic review of literature by searching for prospective observational studies enrolling consecutive patients presenting to the Emergency Department because of syncope. The outcomes considered were syncope recurrence and short- and long-term mortality. Morbidity and a composite of morbidity and mortality were also assessed. Pooled event rates and 95% confidence intervals (CI) were calculated for each outcome using the random effects model. Twenty-five studies (11 158 patients) were included. The incidence of syncope relapse linearly increased from 0.3% at 30 days to 22% at 2 years follow-up. One-year mortality rate varied between 5.7 and 15.5%; the pooled estimate was 8.4% (95% CI: 6.7–10.2%). The incidence of adverse events (morbidity) varied between 6.1 and 25.2% at 10 days and 2 years, respectively. The short-term (10 days) pooled incidence of the composite of morbidity and mortality was 9.1% (95% CI: 6.6–12.5%). We found a high statistical heterogeneity between studies. Conclusion This meta-analysis of prospective observational studies shows that the chance of being asymptomatic linearly progressively decreased over time after the first syncope. Short-term (10–30 days) mortality after syncope was

Syncope is usually addressed in the Emergency Department (ED) by the doctor in charge of the clinical picture, i.e. the patient's risk is stratified, a diagnostic work-up is done and a prognosis is set. Patients are ultimately admitted to hospital or discharged. However, other aspects related to syncope may deeply affect their daily lives. These include how and when to return to work and to driving, the feelings about a recent loss of consciousness, and the potential relapse of syncope. This is particularly significant if the work setting is intrinsically hazardous. These patients need adequate clinical and psychological support. For patients with syncope, two main parameters should be considered regarding returning to work and to driving. The first is to evaluate the risk of syncope recurrence and the second is to consider the expected harm if syncope does indeed occur during these activities. In the present paper we detail the problem of driving (including professional driving) and work after syncope. We propose a new quantitative model that will guide the physician in stratifying the risk for patients who have had a previous syncope event. The new model considers the syncope recurrence risk, the job task duration, and features that facilitate a syncope during work. On the basis of these variables, the global risk index for a worker is calculated. Following appropriate validation, this method might help ED and occupational physicians in their decision-making process with the goal of safely readmitting syncope patients to the workplace.

Motor impairment in Parkinson's disease (PD) is partly due to defective central processing of lower limb afferents. Concomitant alterations in cardiovascular autonomic control leading to orthostatic hypotension may worsen motor ability. We evaluated whether mechanical activation of feet sensory afferents could improve gait and modify the response of cardiovascular autonomic control to stressors in 16 patients (age 66 ± 2 yr) with idiopathic PD (Hoehn & Yhar scale 2–3) on their usual therapy. Eight subjects ( group A) were randomized to undergo skin pressure (0.58 ± 0.04 kg/mm2) stimulation at the hallux tip and first metatarsal joint (effective stimulation; ES) of both feet. Eight remaining patients ( group B) underwent sham stimulation (SS) followed by ES. Three-dimensional movement analysis provided quantitative indexes of movement disability before (baseline) and 24 h after ES and SS. Spectral analysis of heart rate and blood pressure variability provided markers of cardiac sympatho-vagal (LF/HF) and vascular sympathetic (LFSAP) modulations. Markers were measured at rest and during 75° head-up tilt, before and 24 h after ES and SS. After ES, step length and gait velocity increased, upright rotation velocity was enhanced, and step number was decreased. After ES, LFSAP declined. The increase in LF/HF and LFSAP induced by tilt was greater than before feet stimulation. No changes in gait and autonomic parameters were observed after SS. Twenty-four hours after ES, patients with PD showed improved gait and increased cardiac and vascular sympathetic modulation during upright position compared with baseline. Conversely, SS was ineffective on both movement and autonomic parameters, indicating a site specificity effect of the stimulation.

Syncope is a frequent reason for medical consultation and hospital admission and is associated with high health service use and costs.1 ,2 From the pathophysiological standpoint, syncope is a transient loss of consciousness due to transient global cerebral hypoperfusion and can be the final common pathway of different conditions, whose prognosis is highly heterogeneous.3 Indeed, cardiovascular syncope (due to bradyarrhythmias or tachyarrhythmias or structural heart disease) is associated with significant morbidity and mortality, while the prognosis of reflex syncope (vasovagal, situational and carotid sinus syndrome) and syncope due to orthostatic hypotension is generally benign.4 Implantable loop recorders (ILRs) are small devices implanted or injected subcutaneously in the left side of the chest under local anaesthesia. They continuously record and delete a bipolar ECG signal with no need for intravascular leads and have a battery capable of storing significant events for up to 36 months. Thanks to their ability to register the patients' ECG during spontaneous symptoms, ILRs have gained popularity and are now recommended as an early diagnostic tool in the evaluation of unexplained syncope.3 However, randomised clinical trials (RCTs) proving that an ILR-guided diagnosis and treatment changes clinically relevant outcomes, besides increasing the diagnostic rate, are essential to support their use in clinical practice. We conducted a Cochrane review of RCTs to compare ILRs and …

Background The most recent syncope guideline recommends that implantable loop recorders (ILRs) are implanted in the early phase of evaluation of people with recurrent syncope of uncertain origin in the absence of high-risk criteria, and in high-risk patients after a negative evaluation. Observational and case-control studies have shown that loop recorders lead to earlier diagnosis and reduce the rate of unexplained syncopes, justifying their use in clinical practice. However, only randomised clinical trials with an emphasis on a primary outcome of specific ILR-guided diagnosis and therapy, rather than simply electrocardiogram (ECG) diagnosis, might change clinical practice. Objectives To assess the incidence of mortality, quality of life, adverse events and costs of ILRs versus conventional diagnostic workup in people with unexplained syncope. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2015), MEDLINE, EMBASE, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) Search Portal in April 2015. No language restriction was applied. Selection criteria We included all randomised controlled trials of adult participants (i.e. ≥ 18 years old) with a diagnosis of unexplained syncope comparing ILR with standard diagnostic workup. Data collection and analysis Two independent review authors screened titles and abstracts of all potential studies we identified as a result of the literature search, extracted study characteristics and outcome data from included studies and assessed risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We contacted authors of trials for missing data. We analysed dichotomous data (all-cause mortality and aetiologic diagnosis) as risk ratios (RR) with 95% confidence intervals (CI). We used the Chi2 test to assess statistical heterogeneity (with P < 0.1) and the I² statistic to measure heterogeneity among the trials. We created a 'Summary of findings' table using the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness and publication bias) to assess the quality of a body of evidence as it relates to the studies which contribute data to the meta-analyses for the prespecified outcomes. Main results We included four trials involving a total of 579 participants. With the limitation that only two studies reported data on mortality and none of them had considered death as a primary endpoint, the meta-analysis showed no evidence of a difference in the risk of long-term mortality between participants who received ILR and those who were managed conventionally at follow-up (RR 0.97, 95% CI 0.41 to 2.30; participants = 255; studies = 2; very low quality evidence) with no evidence of heterogeneity. No data on short term mortality were available. Two studies reported data on adverse events after ILR implant. Due to the lack of data on adverse events in one of the studies' arms, a formal meta-analysis was not performed for this outcome. Data from two trials seemed to show no difference in quality of life, although this finding was not supported by a formal analysis due to the differences in both the scores used and the way the data were reported. Data from two studies seemed to show a trend towards a reduction in syncope relapses after diagnosis in participants implanted with ILR. Cost analyses from two studies showed higher overall mean costs in the ILR group, if the costs incurred by the ILR implant were counted. The mean cost per diagnosis and the mean cost per arrhythmic diagnosis were lower for participants randomised to ILR implant. Participants who underwent ILR implantation experienced higher rates of diagnosis (RR (in favour of ILR) 0.61, 95% CI 0.54 to 0.68; participants = 579; studies = 4; moderate quality evidence), as compared to participants in the standard assessment group, with no evidence of heterogeneity. Authors' conclusions Our systematic review shows that there is no evidence that an ILR-based diagnostic strategy reduces long-term mortality as compared to a standard diagnostic assessment (very low quality evidence). No data were available for short-term all-cause mortality. Moderate quality evidence shows that an ILR-based diagnostic strategy increases the rate of aetiologic diagnosis as compared to a standard diagnostic pathway. No conclusive data were available on the other end-points analysed. Further trials evaluating the effect of ILRs in the diagnostic strategy of people with recurrent unexplained syncope are warranted. Future research should focus on the assessment of the ability of ILRs to change clinically relevant outcomes, such as quality of life, syncope relapse and costs.

BackgroundFor secondary prevention of fatal and non-fatal cardio-vascular events, benefits of aspirin (ASA) are well defined,and form the basis for current clinical practice [1–4]. Inpatients without a history of cardiovascular diseases(CVD), in contrast, the picture is not clear: several meta-analyses [5, 6] and the individual data meta-analysis ofthe antithrombotic trialists’ (ATT) collaboration [7] showthat the efficacy of ASA in reducing the risks of acutemyocardial infarction (MI) and ischemic stroke does notoutweigh the associated increased risk of bleeding. Theconflicting recommendations from guidelines panels reflectthis uncertainty [3, 8, 9]. After the publication of ATTstudy in 2009 [7], three more randomized controlledstudies (RCT) evaluating the use of ASA in primary pre-vention were published [10–12]. Recently, three nearlycontemporaneous meta-analyses [13–15] combined old andnewest trials’ results.SummaryWe discuss three meta-analyses published between January2011 and 2012 that evaluated trials in primary cardiovas-cular prevention and involved a randomized comparison ofASA versus placebo or control [13–15].The first was carried out by Berger et al., who searchedelectronic databases (MEDLINE, the Cochrane CentralRegister of Controlled Trials, and EMBASE) for RCTspublished up to 2011 [13]. The occurrence of a majorcardiovascular event (MCE), i.e. non-fatal MIs, non-fatalstrokes, all-cause and cardiovascular mortality, was chosenas primary outcome. As primary safety outcomes, theauthors included major bleedings as defined by each study.All outcomes were analysed using the data reported in theoriginal publications. Random effect meta-analysis wasexecuted, using risk ratio (RR) as efficacy measure. Sen-sitivity analysis was performed and specific subsets ofstudies were analysed (removing one by one trials enrollingpatients with diabetes or subclinical atherosclerosis andthose including extended or controlled release aspirin).Meta-regression was applied to evaluate potential effectmodifiers (year of study publication, baseline cardiovas-cular risk, mean age and sex of trial’s participants, and doseof ASA). Potential publication biases were examined byconstructing a funnel plot. Nine prospective randomizedtrials involving 102,621 participants (52,145 allocated toaspirin, 50,476 to placebo/control) were identified forinclusion and meta-analysed.The same nine trials were incorporated in the meta-analysis by Raju et al. [14]. Medline, Cinahl, Embase andthe Cochrane Library databases were sought up to May2010, bibliographies of journal articles were hand-sear-ched and experts were contacted to identify unpublishedstudies. Raju et al. considered the following outcomes

BACKGROUND Atrial fibrillation (AF) is the most common sustained arrhythmia. It occurs in 1%-2% of the general population and its prevalence increases with age. Dronedarone, a noniodinated benzofuran similar to amiodarone, was developed as an antiarrhythmic agent for patients with atrial fibrillation. The aim of our systematic review was to critically evaluate randomized controlled trials that compared treatment with dronedarone versus placebo or amiodarone in patients with atrial fibrillation. METHODS Electronic databases (MEDLINE, Embase, and Central) were searched up to November 2011 with no language restrictions. We included randomized controlled trials in which dronedarone was compared to placebo or other drugs in patients with AF. Internal and external validity was assessed. RESULTS We identified seven papers corresponding to eight randomized controlled trials. The DAFNE, EURIDIS/ADONIS, and ATHENA trials demonstrated a reduction of AF recurrence with dronedarone as compared to placebo in patients with nonpermanent AF. The DIONYSOS study showed that dronedarone is less effective for the prevention of recurrent AF but improved tolerability as compared to amiodarone. Considering patients with permanent AF, the ERATO trial showed that dronedarone had rate-control effects while the PALLAS study was stopped early since stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes were significantly more frequent in subjects treated with dronedarone as compared to placebo. The ANDROMEDA trial included patients with recent hospitalization for heart failure and was terminated early because of excess of deaths in the dronedarone group. CONCLUSION Like most antiarrhythmic drugs, dronedarone reduces the recurrence of AF in patients with paroxysmal or persistent AF as compared to placebo. However, relapse rates in the first year of therapy are high. Moreover, dronedarone showed to be less effective than amiodarone. Finally, dronedarone should be avoided in patients with permanent AF and a high risk for cardiovascular events or severe congestive heart failure.

The study aimed to compare the efficacy of the Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL) risk score, San Francisco Syncope Rule, and clinical judgment in assessing the short-term prognosis of syncope.We studied 488 patients consecutively seen for syncope at the emergency department of 2 general hospitals between January and July 2004. Sensitivity, specificity, predictive values, and likelihood ratios for short-term (within 10 days) severe outcomes were computed for each decision rule and clinical judgment. Severe outcomes comprised death, major therapeutic procedures, and early readmission to hospital.Clinical judgment had a sensitivity of 77%, a specificity of 69%, and would have admitted less patients (34%, P.05 vs decision rules). The OESIL risk score was characterized by a sensitivity of 88% and a specificity of 60% (admission 43%). San Francisco Syncope Rule sensitivity was 81% and specificity was 63% (admission 40%). According to both clinical rules, no discharged patient would have died. With combined OESIL risk score and clinical judgment, the probability of adverse events was 0.7% for patients with both low risk scores, whereas that for both high risk scores was roughly 16%.Because of a relatively low sensitivity, both risk scores were partially lacking in recognizing patients with short-term high-risk syncope. However, the application of the decision rules would have identified all patients who subsequently died, and OESIL risk score and clinical judgment combined seem to improve the decision-making process concerning the identification of high-risk patients who deserve admission.

A total of 676 subjects were included in the study. Forty-one subjects (6.1%) experienced severe outcomes (5 deaths, 0.7%; 36 major therapeutic procedures, 5.4%) in the 10 days after presentation. An abnormal electrocardiogram, concomitant trauma, absence of symptoms of impending syncope, and male gender were associated with short-term unfavorable outcomes. Long-term severe outcomes were 9.3% (40 deaths, 6.0%; 22 major therapeutic procedures, 3.3%), and their occurrence was correlated with an age 65 years, history of neoplasms, cerebrovascular diseases, structural heart diseases, and ventricular arrhythmias. Short-term major therapeutic procedures were more common (p 0.05) in subjects who had been admitted to hospital (13.3%) than in discharged (1.6%), whereas mortality was similar. One-year mortality was greater (p 0.05) in admitted (14.7%) than in discharged (1.8%) patients.

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