Consequences of the lack of clinical forensic medicine in emergency departments.

Most victims of physical violence sooner or later will access a hospital or medical cabinet because of that violence, and in particular emergency departments (EDs). This paper aims to analyze the performance of emergency ward clinicians in the forensic management of such victims by examining the activities carried out and the data reported. A total of 991 medical records were extrapolated from the database of the ED of the Policlinico of Milan in an average pre-pandemic 1-year activity. For each medical record, 16 parameters were analyzed in-depth including epidemiological data, information on the type of violent actions, injuries, and time between the infliction of the lesion and access to the ED. In the vast majority of cases, all the actions with medicolegal implications had been neglected by health professionals causing loss of data not only for the justice system but especially for correctly interpreting what happened and taking appropriate measures to protect the patient/victim. Hence, given that clinicians in EDs are busy with non-forensic clinical tasks (and rightly so), it should be ensured that there be specific forensic clinical personnel. However, it is crucial that when unfortunately there can be no forensic staff, at least the clinicians who work in the ED are properly trained to correctly apply essential medicolegal measures. Overall, timely and informed medical and forensic intervention is possible and necessary for the improvement and maintenance of the mental and physical health of victims of violence.

Mental health and the effects on methylation of stress-related genes in front-line versus other health care professionals during the second wave of COVID-19 pandemic: an Italian pilot study.

Healthcare workers experienced high degree of stress during COVID-19. Purpose of the present article is to compare mental health (depressive and Post-Traumatic-Stress-Disorders-PTSD-symptoms) and epigenetics aspects (degree of methylation of stress-related genes) in front-line healthcare professionals versus healthcare working in non-COVID-19 wards. Sixty-eight healthcare workers were included in the study: 39 were working in COVID-19 wards (cases) and 29 in non-COVID wards (controls). From all participants, demographic and clinical information were collected by an ad-hoc questionnaire. Depressive and PTSD symptoms were evaluated by the Patient Health Questionnaire-9 (PHQ-9) and the Impact of Event Scale-Revised (IES-R), respectively. Methylation analyses of 9 promoter/regulatory regions of genes known to be implicated in depression/PTSD (ADCYAP1, BDNF, CRHR1, DRD2, IGF2, LSD1/KDM1A, NR3C1, OXTR, SLC6A4) were performed on DNA from blood samples by the MassARRAY EpiTYPER platform, with MassCleave settings. Controls showed more frequent lifetime history of anxiety/depression with respect to cases (χ2 = 5.72, p = 0.03). On the contrary, cases versus controls presented higher PHQ-9 (t = 2.13, p = 0.04), PHQ-9 sleep item (t = 2.26, p = 0.03), IES-R total (t = 2.17, p = 0.03), IES-R intrusion (t = 2.46, p = 0.02), IES-R avoidance (t = 1.99, p = 0.05) mean total scores. Methylation levels at CRHR1, DRD2 and LSD1 genes was significantly higher in cases with respect to controls (p < 0.01, p = 0.03 and p = 0.03, respectively). Frontline health professionals experienced more negative effects on mental health during COVID-19 pandemic than non-frontline healthcare workers. Methylation levels were increased in genes regulating HPA axis (CRHR1) and dopamine neurotransmission (DRD2 and LSD1), thus supporting the involvement of these biological processes in depression/PTSD and indicating that methylation of these genes can be modulated by stress conditions, such as working as healthcare front-line during COVID-19 pandemic.

Choosing Wisely in clinical practice: Embracing critical thinking, striving for safer care.

In recent years, the Choosing Wisely and Less is More campaigns have gained growing attention in the medical scientific community. Several projects have been launched to facilitate confrontation among patients and physicians, to achieve better and harmless patient-centered care. Such initiatives have paved the way to a new "way of thinking." Embracing such a philosophy goes through a cognitive process that takes into account several issues. Medicine is a highly inaccurate science and physicians should deal with uncertainty. Evidence from the literature should not be accepted as it is but rather be translated into practice by medical practitioners who select treatment options for specific cases based on the best research, patient preferences, and individual patient characteristics. A wise choice requires active effort into minimizing the chance that potential biases may affect our clinical decisions. Potential harms and all consequences (both direct and indirect) of prescribing tests, procedures, or medications should be carefully evaluated, as well as patients' needs and preferences. Through such a cognitive process, a patient management shift is needed, moving from being centered on establishing a diagnosis towards finding the best management strategy for the right patient at the right time. Finally, while "thinking wisely," physicians should also "act wisely," being among the leading actors in facing upcoming healthcare challenges related to environmental issues and social discrepancies.

Prognostic value of copeptin and mid-regional proadrenomedullin in COVID-19-hospitalized patients.

BACKGROUND: Biomarkers are used for diagnosis, risk stratification and medical decisions. Copeptin and mid-regional proadrenomedullin (MR-proADM) are markers of stress and endothelial function, respectively, which have been studied in pneumonia, sepsis and septic shock. This study aimed to assess whether copeptin and MR-proADM could predict coronavirus disease 2019 (COVID-19) in-hospital outcomes, that is multi-system complications, length of stay and mortality. METHODS: Copeptin and MR-proADM were assessed at admission in 116 patients hospitalized with COVID-19. Data were retrospectively extracted from an online database. The primary endpoint was in-hospital mortality. The secondary endpoints were in-hospital complications, the composite outcome 'death, or admission to intensive care unit, or in-hospital complications', and length of stay. The predictive power was expressed as area under the receiver operator characteristic curve (AUROC). RESULTS: Copeptin was increased in non-survivors (median 29.7 [interquartile range 13.0-106.2] pmol/L) compared to survivors (10.9 [5.9-25.3] pmol/L, p < 0.01). The AUROC for mortality was 0.71, with a hazard ratio of 3.67 (p < 0.01) for copeptin values > 25.3 pmol/L. MR-proADM differentiated survivors (0.8 [0.6-1.1] nmol/L) from non-survivors (1.5 [1.1-2.8] nmol/L, p < 0.001) and yielded a AUROC of 0.79 and a hazard ratio of 7.02 (p < 0.001) for MR-proADM values > 1.0 nmol/L. Copeptin and MR-proADM predicted sepsis (AUROC 0.95 and 0.96 respectively), acute kidney injury (0.87 and 0.90), the composite outcome (0.69 and 0.75) and length of stay (r = 0.42, p < 0.001, and r = 0.46, p < 0.001). CONCLUSIONS: Admission MR-proADM and copeptin may be implemented for early risk stratification in COVID-19-hospitalized patients to help identify those eligible for closer monitoring and care intensification.

Prospective comparison of AMB, GAP AND START scores and triage nurse clinical judgement for predicting admission from an ED: a single-centre prospective study.

BACKGROUND: It is postulated that early determination of the need for admission can improve flow through EDs. There are several scoring systems which have been developed for predicting patient admission at triage, although they have not been directly compared. In addition, it is not known if these scoring systems perform better than clinical judgement. Therefore, the aim of this study was to validate existing tools in predicting hospital admission during triage and then compare them with the clinical judgement of triage nurses. METHODS: To conduct this prospective, single-centre observational study, we enrolled consecutive adult patients who presented between 30 September 2019 and 25 October 2019 at the ED of a large teaching hospital in Milan, Italy. For each patient, triage nurses recorded all of the variables needed to perform Ambulatory (AMB), Glasgow Admission Prediction (GAP) and Sydney Triage to Admission Risk Tool (START) scoring. The probability of admission was estimated by the triage nurses using clinical judgement and expressed as a percentage from 0 to 100 with intervals of 5. Nurse estimates were dichotomised for analysis, with ≥50% likelihood being a prediction of admission. Receiver operating characteristic curves were generated for accuracy of the predictions. Area under the curve (AUC) with 95% CI for each of the scores and for the nursing judgements was also calculated. RESULTS: A total of 1710 patients (844 men; median age, 54 years (IQR: 34-75)) and 35 nurses (15 men; median age, 37 years (IQR: 33-48)) were included in this study. Among these patients, 310 (18%) were admitted to hospital from the ED. AUC values for AMB, GAP and START scores were 0.77 (95% CI: 0.74 to 0.79), 0.72 (95% CI: 0.69 to 0.75) and 0.61 (95% CI: 0.58 to 0.64), respectively. The AUC for nurse clinical judgement was 0.86 (95% CI: 0.84 to 0.89). CONCLUSION: AMB, GAP and START scores provided moderate accuracy in predicting patient admission. However, all of the scores were significantly worse than the clinical judgement of the triage nurses.

Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: An observational cohort study.

BACKGROUND: Immunomodulants have been proposed to mitigate severe acute respiratory syndrome coronavirus 2-induced cytokine storm, which drives acute respiratory distress syndrome in coronavirus disease 2019 (COVID-19). OBJECTIVE: We sought to determine efficacy and safety of the association of IL-1 receptor antagonist anakinra plus methylprednisolone in severe COVID-19 pneumonia with hyperinflammation. METHODS: A secondary analysis of prospective observational cohort studies was carried out at an Italian tertiary health care facility. COVID-19 patients consecutively hospitalized (February 25, 2020, to March 30, 2020) with hyperinflammation (ferritin ≥1000 ng/mL and/or C-reactive protein >10 mg/dL) and respiratory failure (oxygen therapy from 0.4 FiO2 Venturi mask to invasive mechanical ventilation) were evaluated to investigate the effect of high-dose anakinra plus methylprednisolone on survival. Patients were followed from study inclusion to day 28 or death. Crude and adjusted (sex, age, baseline PaO2:FiO2 ratio, Charlson index, baseline mechanical ventilation, hospitalization to inclusion lapse) risks were calculated (Cox proportional regression model). RESULTS: A total of 120 COVID-19 patients with hyperinflammation (median age, 62 years; 80.0% males; median PaO2:FiO2 ratio, 151; 32.5% on mechanical ventilation) were evaluated. Of these, 65 were treated with anakinra and methylprednisolone and 55 were untreated historical controls. At 28 days, mortality was 13.9% in treated patients and 35.6% in controls (Kaplan-Meier plots, P = .005). Unadjusted and adjusted risk of death was significantly lower for treated patients compared with controls (hazard ratio, 0.33, 95% CI, 0.15-0.74, P = .007, and HR, 0.18, 95% CI, 0.07-0.50, P = .001, respectively). No significant differences in bloodstream infections or laboratory alterations were registered. CONCLUSIONS: Treatment with anakinra plus methylprednisolone may be a valid therapeutic option in COVID-19 patients with hyperinflammation and respiratory failure, also on mechanical ventilation. Randomized controlled trials including the use of either agent alone are needed to confirm these results.

Complement activation and endothelial perturbation parallel COVID-19 severity and activity.

BACKGROUND: Animal models and few clinical reports suggest the involvement of the complement system in the onset of severe manifestations of coronavirus disease-2019 (COVID-19). However, complement contribution to endotheliopathy and hypercoagulability has not been elucidated yet. OBJECTIVE: To evaluate the association among complement activation, endothelial damage and disease severity or activity in COVID-19 patients. METHODS: In this single-centre cohort study, 148 patients with COVID-19 of different severity were evaluated upon hospital admission and 30 days later. Markers of complement activation (SC5b-9 and C5a) and endothelial perturbation (von Willebrand factor [vWF], tissue-type plasminogen activator [t-PA], plasminogen activator inhibitor-1 [PAI-1], soluble thrombomodulin [sTM], and soluble endothelial selectin [sE-selectin]) were measured in plasma. RESULTS: The patients had high plasma levels of SC5b-9 and C5a (p = 0.0001 for both) and vWF, t-PA and PAI-1 (p = 0.0001 for all). Their SC5b-9 levels correlated with those of vWF (r = 0.517, p = 0.0001) and paralleled disease severity (severe vs mild p = 0.0001, severe vs moderate p = 0.026 and moderate vs mild p = 0.001). The levels of sE-selectin were significantly increased only in the patients with severe disease. After 30 days, plasma SC5b-9, C5a and vWF levels had significantly decreased (p = 0.0001 for all), and 43% of the evaluated patients had normal levels. CONCLUSIONS: Complement activation is boosted during the progression of COVID-19 and dampened during remission, thus indicating its role in the pathophysiology of the disease. The association between complement activation and the biomarkers of endothelial damage suggests that complement may contribute to tissue injury and could be the target of specific therapy.

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.

Variations in volume of emergency surgeries and emergency department access at a third level hospital in Milan, Lombardy, during the COVID-19 outbreak.

BACKGROUND: During the recent outbreak of COVID-19 (coronavirus disease 2019), Lombardy was the most affected region in Italy, with 87,000 patients and 15,876 deaths up to May 26, 2020. Since February 22, 2020, well before the Government declared a state of emergency, there was a huge reduction in the number of emergency surgeries performed at hospitals in Lombardy. A general decrease in attendance at emergency departments (EDs) was also observed. The aim of our study is to report the experience of the ED of a third-level hospital in downtown Milan, Lombardy, and provide possible explanations for the observed phenomena. METHODS: This retrospective, observational study assessed the volume of emergency surgeries and attendance at an ED during the course of the pandemic, i.e. immediately before, during and after a progressive community lockdown in response to the COVID-19 pandemic. These data were compared with data from the same time periods in 2019. The results are presented as means, standard error (SE), and 95% studentized confidence intervals (CI). The Wilcoxon rank signed test at a 0.05 significance level was used to assess differences in per-day ED access distributions. RESULTS: Compared to 2019, a significant overall drop in emergency surgeries (60%, p < 0.002) and in ED admittance (66%, p ≅ 0) was observed in 2020. In particular, there were significant decreases in medical (40%), surgical (74%), specialist (ophthalmology, otolaryngology, traumatology, and urology) (92%), and psychiatric (60%) cases. ED admittance due to domestic violence (59%) and individuals who left the ED without being seen (76%) also decreased. Conversely, the number of deaths increased by 196%. CONCLUSIONS: During the COVID-19 outbreak the volume of urgent surgeries and patients accessing our ED dropped. Currently, it is not known if mortality of people who did not seek care increased during the pandemic. Further studies are needed to understand if such reductions during the COVID-19 pandemic will result in a rebound of patients left untreated or in unwanted consequences for population health.

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.

Structural magnetic resonance imaging for the early diagnosis of dementia due to Alzheimer's disease in people with mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) due to Alzheimer's disease is the symptomatic predementia phase of Alzheimer's disease dementia, characterised by cognitive and functional impairment not severe enough to fulfil the criteria for dementia. In clinical samples, people with amnestic MCI are at high risk of developing Alzheimer's disease dementia, with annual rates of progression from MCI to Alzheimer's disease estimated at approximately 10% to 15% compared with the base incidence rates of Alzheimer's disease dementia of 1% to 2% per year. OBJECTIVES: To assess the diagnostic accuracy of structural magnetic resonance imaging (MRI) for the early diagnosis of dementia due to Alzheimer's disease in people with MCI versus the clinical follow-up diagnosis of Alzheimer's disease dementia as a reference standard (delayed verification). To investigate sources of heterogeneity in accuracy, such as the use of qualitative visual assessment or quantitative volumetric measurements, including manual or automatic (MRI) techniques, or the length of follow-up, and age of participants. MRI was evaluated as an add-on test in addition to clinical diagnosis of MCI to improve early diagnosis of dementia due to Alzheimer's disease in people with MCI. SEARCH METHODS: On 29 January 2019 we searched Cochrane Dementia and Cognitive Improvement's Specialised Register and the databases, MEDLINE, Embase, BIOSIS Previews, Science Citation Index, PsycINFO, and LILACS. We also searched the reference lists of all eligible studies identified by the electronic searches. SELECTION CRITERIA: We considered cohort studies of any size that included prospectively recruited people of any age with a diagnosis of MCI. We included studies that compared the diagnostic test accuracy of baseline structural MRI versus the clinical follow-up diagnosis of Alzheimer's disease dementia (delayed verification). We did not exclude studies on the basis of length of follow-up. We included studies that used either qualitative visual assessment or quantitative volumetric measurements of MRI to detect atrophy in the whole brain or in specific brain regions, such as the hippocampus, medial temporal lobe, lateral ventricles, entorhinal cortex, medial temporal gyrus, lateral temporal lobe, amygdala, and cortical grey matter. DATA COLLECTION AND ANALYSIS: Four teams of two review authors each independently reviewed titles and abstracts of articles identified by the search strategy. Two teams of two review authors each independently assessed the selected full-text articles for eligibility, extracted data and solved disagreements by consensus. Two review authors independently assessed the quality of studies using the QUADAS-2 tool. We used the hierarchical summary receiver operating characteristic (HSROC) model to fit summary ROC curves and to obtain overall measures of relative accuracy in subgroup analyses. We also used these models to obtain pooled estimates of sensitivity and specificity when sufficient data sets were available. MAIN RESULTS: We included 33 studies, published from 1999 to 2019, with 3935 participants of whom 1341 (34%) progressed to Alzheimer's disease dementia and 2594 (66%) did not. Of the participants who did not progress to Alzheimer's disease dementia, 2561 (99%) remained stable MCI and 33 (1%) progressed to other types of dementia. The median proportion of women was 53% and the mean age of participants ranged from 63 to 87 years (median 73 years). The mean length of clinical follow-up ranged from 1 to 7.6 years (median 2 years). Most studies were of poor methodological quality due to risk of bias for participant selection or the index test, or both. Most of the included studies reported data on the volume of the total hippocampus (pooled mean sensitivity 0.73 (95% confidence interval (CI) 0.64 to 0.80); pooled mean specificity 0.71 (95% CI 0.65 to 0.77); 22 studies, 2209 participants). This evidence was of low certainty due to risk of bias and inconsistency. Seven studies reported data on the atrophy of the medial temporal lobe (mean sensitivity 0.64 (95% CI 0.53 to 0.73); mean specificity 0.65 (95% CI 0.51 to 0.76); 1077 participants) and five studies on the volume of the lateral ventricles (mean sensitivity 0.57 (95% CI 0.49 to 0.65); mean specificity 0.64 (95% CI 0.59 to 0.70); 1077 participants). This evidence was of moderate certainty due to risk of bias. Four studies with 529 participants analysed the volume of the total entorhinal cortex and four studies with 424 participants analysed the volume of the whole brain. We did not estimate pooled sensitivity and specificity for the volume of these two regions because available data were sparse and heterogeneous. We could not statistically evaluate the volumes of the lateral temporal lobe, amygdala, medial temporal gyrus, or cortical grey matter assessed in small individual studies. We found no evidence of a difference between studies in the accuracy of the total hippocampal volume with regards to duration of follow-up or age of participants, but the manual MRI technique was superior to automatic techniques in mixed (mostly indirect) comparisons. We did not assess the relative accuracy of the volumes of different brain regions measured by MRI because only indirect comparisons were available, studies were heterogeneous, and the overall accuracy of all regions was moderate. AUTHORS' CONCLUSIONS: The volume of hippocampus or medial temporal lobe, the most studied brain regions, showed low sensitivity and specificity and did not qualify structural MRI as a stand-alone add-on test for an early diagnosis of dementia due to Alzheimer's disease in people with MCI. This is consistent with international guidelines, which recommend imaging to exclude non-degenerative or surgical causes of cognitive impairment and not to diagnose dementia due to Alzheimer's disease. In view of the low quality of most of the included studies, the findings of this review should be interpreted with caution. Future research should not focus on a single biomarker, but rather on combinations of biomarkers to improve an early diagnosis of Alzheimer's disease dementia.

Incremental Risk of Intracranial Hemorrhage After Mild Traumatic Brain Injury in Patients on Antiplatelet Therapy: Systematic Review and Meta-Analysis.

BACKGROUND: Mild traumatic brain injury (TBI) is a common event and antiplatelet therapy might represent a risk factor for bleeding. OBJECTIVE: The aim of this study was to evaluate the risk of intracranial hemorrhage (ICH) after mild TBI in patients on antiplatelet therapy through a systematic review and meta-analysis. METHODS: We conducted a systematic review and meta-analysis of prospective and retrospective observational studies on patients with mild TBI on antiplatelet therapy vs. those not on any antithrombotic therapy. The primary outcome was the risk of ICH in patients with mild TBI based on the first computed tomography scan. Secondary outcome was the risk of mortality and neurosurgery. RESULTS: Nine studies and 14,545 patients were included. The incidence of ICH ranged from 3.6% to 29.4% in the antiplatelet group and from 1.6% to 21.1% in the control group. Patients on antiplatelet therapy had a higher risk of ICH after a mild TBI compared with patients that were not on antithrombotic therapy (risk ratio 1.51; 95% confidence interval 1.21-1.88). No difference was found in the composite outcome of mortality and neurosurgery. CONCLUSIONS: Patients on antiplatelet therapy have an increased risk of ICH after mild TBI compared with patients not on antithrombotic therapy. However, the risk is just slightly increased, and the need to perform a computed tomography scan in patients on antiplatelet therapy after a mild TBI should be evaluated case by case, but always considered in patients with other risk factors.

Diagnostic accuracy of ICD-9 code 780.2 for the identification of patients with syncope in the emergency department.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

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

Wrong guidelines: how to detect them and what to do in the case of flawed recommendations.

Any evidence-based recommendation needs careful assessment of its methodological background as well as of its content trustworthiness, especially given that following it will not necessarily produce the intended clinical outcomes. There are no established instruments to evaluate guidelines for their content, while useful tools assessing the quality of methods followed are well recognised and adopted. We suggest a 'safety bundle' considering methodological aspects and content trustworthiness of guidelines, by adopting the GRADE method in a backward fashion. Sharing the critical analysis of the guidelines with patients, including any eventual uncertainty about them, is of key importance in order to avoid the possible adverse effects derived from following the wrong guidelines. Such critical approach is also helpful and beneficial in producing better care pathways, health policy decisions and more relevant and ethical research.

Implantable loop recorder versus conventional diagnostic workup for unexplained recurrent syncope.

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 Chi(2) 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.

Syncope recurrence and mortality: a systematic review.

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 <2% and that the overall 10-day rate of the composite endpoint of death and major events was ∼9%. The knowledge of syncope prognosis could help clinicians to understand syncope patients' prognosis and researchers to design future studies.

Standard and pocket-size lung ultrasound devices can detect interstitial lung disease in rheumatoid arthritis patients.

OBJECTIVES: Interstitial lung disease (ILD) is a frequent extra-articular manifestation of RA associated with increased mortality. High-resolution CT (HRCT) is used for diagnosis and follow-up, but its accuracy is counterbalanced by high costs and radiological risk. In the presence of ILD, lung US (LUS) detects vertical artefacts called B-lines. The aims of the present study were to evaluate the accuracy of LUS in the diagnosis of ILD in RA and to validate the use of a pocket-size US device (PS-USD) as a screening tool. METHODS: LUS was performed with standard equipment by a trained physician through longitudinal scans following anatomical lines: 72 segments were considered (28 anteriorly and 44 posteriorly) and B-lines were counted in each segment. A B-lines score >10 identified a positive examination (presence of ILD). A second LUS session for positive/negative judgment was performed by a short-trained physician using a PS-USD. RESULTS: Thirty-nine patients were studied. The sensitivity and specificity of standard LUS vs HRCT were 92% and 56%, respectively. The B-line score was significantly correlated with HRCT score (r = 0.806). A total of 29 patients were studied with a PS-USD. Sensitivity and specificity for PS-USD vs HRCT were 89% and 50%. CONCLUSION: The sensitivity of LUS in the detection of ILD supports its use as a screening test for ILD in RA patients, even in the ambulatory setting with a PS-USD. The strong correlation between echographic and HRCT scores indicates LUS is a valid tool for grading and follow-up of ILD.