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International audience; Background: Hemoptysis is not common in pulmonary embolism (PE) and lacks specificity for its diagnosis. However, this item is present in different validated scores that estimate the clinical probability of PE. The relevance of this item in clinical decision rules (CDRs) is not clearly established.Objective: The aim of this study was to evaluate the impact of removing the "hemoptysis" item from the PERC, YEARS, and PEGeD CDR in patients with low clinical probability of PE.Design: This was a post hoc analysis of two European prospective cohorts, which included 2968 patients presenting to the ED with a low clinical probability of PE (PROPER and PERCEPIC) and a 3-month follow-up. The primary endpoint was the false-negative rate of a CDR score without the hemoptysis item. Secondary endpoints included the potential reduction of chest imaging if the item hemoptysis was to be removed and risk stratification of the Geneva and Wells scores without the hemoptysis item.Results: Of 2968 patients included (mean ± SD age 46 ± 18 years, 53% female), 87 patients (3%) had a PE diagnosed at 3 months. A total of 2908 were followed-up at 3 months and analyzed. Using the PERC rule with and without the hemoptysis item, there were 13 and 14 missed cases of PE, respectively (failure rate 0.45% [95% CI 0.25%-0.78%] and 0.48% [95% CI 0.27%-0.82%]). Using the YEARS strategy, there were 11 missed PE cases with or without the hemoptysis item (false-negative rate 0.57% [95% CI 0.30%-1.05%]). With the PERC and YEARS rule, removing the hemoptysis item would have led to a 1% reduction in chest imaging. The PEGeD strategy was not modified by the removal of the hemoptysis item.Conclusions: The hemoptysis item could be safely removed from the PERC, YEARS, and PEGeD CDRs. However, there was no subsequent clinically relevant reduction of chest imaging.

Dexmedetomidine is an alternative agent for procedural sedation in the emergency department thanks to its ability to maintain hemodynamic and respiratory stability. Dexmedetomidine must, however, be combined with a powerful analgesic. Our aim was to evaluate the quality and safety of procedural sedation using the combination of dexmedetomidine and ketamine for patients undergoing painful procedures in the emergency department. This prospective interventional single-center study was conducted in an academic emergency department of an urban hospital in Brussels, Belgium. Patients received a bolus injection of 1 µg/kg dexmedetomidine over 10 min and then a continuous infusion of 0.6 µg/kg/h followed by a bolus of 1 mg/kg ketamine. The painful procedure was carried out 1 min later. The level of pain was evaluated with a numerical rating scale from 0 (no pain) to 10 (maximal pain). The level of patient comfort for the procedure was measured using a comfort scale. Thirty patients were included. Overall, 90% of patients felt little or no pain (n = 29 of 30) or discomfort (n = 28 of 30) during the procedure. One patient experienced apnea with desaturation, which was resolved by a jaw-thrust maneuver. Although 23% of patients had significant arterial hypertension, none required drug treatment. The combination of dexmedetomidine and ketamine provides conscious sedation, bringing comfort and pain relief to patients in optimal conditions for respiratory and hemodynamic safety. However, sedation and recovery times are longer than with conventional drug combinations. The dexmedetomidine-ketamine combination should therefore be recommended for nonurgent procedures and fragile patients.

IntroductionCurrent guidelines for patients presenting to the emergency department (ED) with chest pain without ST-segment elevation myocardial infarction (STEMI) on ECG are based on serial troponin measurements. A clinical tool able to identify very low-risk patients who could forgo a troponin test and low-risk patients requiring only one troponin measurement would be of great interest. To do so, the HEAR and HEART score, standing for history, ECG, age, risk factors±troponin were prospectively assessed, but not combined and implemented in clinical practice. The objective of the eCARE study is to assess the impact of implementing a diagnostic strategy based on a HEAR score Methods and analysisStepped-wedge cluster-randomised control trial in 10 EDs. Patients with non-traumatic chest pain and no formal diagnosis were included and followed for 30 days. In the interventional phase, the doctor will be asked not to perform a troponin test to look for an acute coronary if the HEAR score is Ethics and disseminationThe study was approved by an institutional review board for all participating centres. If successful, the eCARE study will cover a gap in the evidence, proving that it is safe and efficient to rule out the hypothesis of an acute myocardial infarction in some selected very low-risk patients or based on a single troponin measurement in some low-risk patients.Trial registration numberNCT04157790.

AIMS: The aim of this study is to compare the Hestia rule vs. the simplified Pulmonary Embolism Severity Index (sPESI) for triaging patients with acute pulmonary embolism (PE) for home treatment. METHODS AND RESULTS: Normotensive patients with PE of 26 hospitals from France, Belgium, the Netherlands, and Switzerland were randomized to either triaging with Hestia or sPESI. They were designated for home treatment if the triaging tool was negative and if the physician-in-charge, taking into account the patient's opinion, did not consider that hospitalization was required. The main outcomes were the 30-day composite of recurrent venous thrombo-embolism, major bleeding or all-cause death (non-inferiority analysis with 2.5% absolute risk difference as margin), and the rate of patients discharged home within 24 h after randomization (NCT02811237). From January 2017 through July 2019, 1975 patients were included. In the per-protocol population, the primary outcome occurred in 3.82% (34/891) in the Hestia arm and 3.57% (32/896) in the sPESI arm (P = 0.004 for non-inferiority). In the intention-to-treat population, 38.4% of the Hestia patients (378/984) were treated at home vs. 36.6% (361/986) of the sPESI patients (P = 0.41 for superiority), with a 30-day composite outcome rate of 1.33% (5/375) and 1.11% (4/359), respectively. No recurrent or fatal PE occurred in either home treatment arm. CONCLUSIONS: For triaging PE patients, the strategy based on the Hestia rule and the strategy based on sPESI had similar safety and effectiveness. With either tool complemented by the overruling of the physician-in-charge, more than a third of patients were treated at home with a low incidence of complications., SCOPUS: ar.j, info:eu-repo/semantics/published

La douleur thoracique est un motif très fréquent de consultation aux urgences. Le diagnostic différentiel est large et regroupe diverses étiologies parmi lesquelles les syndromes coronariens aigus (SCA) qui sont à l’avantplan. L’exclusion d’un SCA demeure une priorité absolue pour l’urgentiste au vu de la morbidité et de la mortalité qui lui sont associées. Afin d’aider le praticien dans sa démarche diagnostique, plusieurs algorithmes ont été élaborés pour exclure et diagnostiquer efficacement un SCA. Ceux-ci intègrent des données cliniques, électrocardiographiques et le dosage de la troponine. Leur utilisation est relativement simple et a été validée dans plusieurs essais cliniques. Ils permettent d’écarter le diagnostic de SCA chez une proportion significative de patients, avec une marge d’erreur très faible. Le score HEART se montre supérieur aux autres scores existants, et son application en salle d’urgences permet d’orienter de manière adéquate la démarche diagnostique, afin de réduire les investigations complémentaires et d’accélérer la prise en charge. Afin d’exclure un SCA sans recourir au dosage de la troponine, la règle CARE a été proposée récemment avec des résultats prometteurs. Issue directement du score HEART, elle permet d’écarter très rapidement le diagnostic de SCA puisqu’elle se passe de dosage biologique tout en gardant un profil de sécurité semblable.

BACKGROUND: The Hospitalization or Outpatient Management of Patients With SARS-CoV-2 Infection (HOME-CoV) rule is a checklist of eligibility criteria for home treatment of patients with COVID-19, defined using a Delphi method. RESEARCH QUESTION: Is the HOME-CoV rule reliable for identifying a subgroup of COVID-19 patients with a low risk of adverse outcomes who can be treated at home safely? STUDY DESIGN AND METHODS: We aimed to validate the HOME-CoV rule in a prospective, multicenter study before and after trial of patients with probable or confirmed COVID-19 who sought treatment at the ED of 34 hospitals. The main outcome was an adverse evolution, that is, invasive ventilation or death, occurring within the 7 days after patient admission. The performance of the rule was assessed by the false-negative rate. The impact of the rule implementation was assessed by the absolute differences in the rate of patients who required invasive ventilation or who died and in the rate of patients treated at home, between an observational and an interventional period after implementation of the HOME-CoV rule, with propensity score adjustment. RESULTS: Among 3,000 prospectively enrolled patients, 1,239 (41.3%) demonstrated a negative HOME-CoV rule finding. The false-negative rate of the HOME-CoV rule was 4 in 1,239 (0.32%; 95% CI, 0.13%-0.84%), and its area under the receiver operating characteristic curve was 80.9 (95% CI, 76.5-85.2). On the adjusted populations, 25 of 1,274 patients (1.95%) experienced an adverse evolution during the observational period vs 12 of 1,274 patients (0.95%) during the interventional period: -1.00 (95% CI, -1.86 to -0.15). During the observational period, 858 patients (67.35%) were treated at home vs 871 patients (68.37%) during the interventional period: -1.02 (95% CI, -4.46 to 2.26). INTERPRETATION: A large proportion of patients treated in the ED with probable or confirmed COVID-19 have a negative HOME-CoV rule finding and can be treated safely at home with a very low risk of complications. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04338841; URL: www.clinicaltrials.gov.

Summary Background The ability of the pulmonary embolism rule-out criteria (PERC) to exclude pulmonary embolism without further testing remains debated outside the USA, especially in the population with suspected pulmonary embolism who have a high prevalence of the condition. Our main objective was to prospectively assess the predictive value of negative PERC to rule out pulmonary embolism among European patients with low implicit clinical probability. Methods We did a multicentre, prospective, observational study in 12 emergency departments in France and Belgium. We included consecutive patients aged 18 years or older with suspected pulmonary embolism. Patients were excluded if they had already been hospitalised for more than 2 days, had curative anticoagulant therapy in progress for more than 48 h, or had a diagnosis of thromboembolic disease documented before admission to emergency department. Physicians completed a standardised case report form comprising implicit clinical probability assessment (low, moderate, or high) and a list of risk factors including criteria of the PERC rule. They were asked to follow international recommendations for diagnostic strategy, masked to PERC assessment. The primary endpoint was the proportion of patients with low implicit clinical probability and negative PERC who had venous thromboembolic events, diagnosed during initial diagnostic work-up or during 3-month follow-up, as externally adjudicated by an independent committee masked to the PERC and clinical probability assessment. The upper limit of the 95% CI around the 3-month thromboembolic risk was set at 3%. We did all analyses by intention to treat, including all patients with complete follow-up. This trial is registered with ClinicalTrials.gov, number NCT02360540. Findings Between May 1, 2015, and April 30, 2016, 1773 consecutive patients with suspected pulmonary embolism were prospectively assessed for inclusion, of whom 1757 were included. 1052 (60%) patients were classed as having low clinical probability, 49 (4·7%, 95% CI 3·5–6·1) of whom had a venous thromboembolic event. In patients with a low implicit clinical probability, 337 (32%) patients had negative PERC, of whom four (1·2%; 95% CI 0·4–2·9) went on to have a pulmonary embolism. Interpretation In European patients with low implicit clinical probability, PERC can exclude pulmonary embolism with a low percentage of false-negative results. The results of our prospective, observational study allow and justify an implementation study of the PERC rule in Europe. Funding French Ministry of Health.

Essentials The reproducibility of Clinical Events Committee (CEC) adjudications is almost unexplored. A random selection of events from a venous thromboembolism trial was blindly re-adjudicated. 'Unexplained sudden deaths' (possible fatal embolism) explained most discordant adjudications. A precise definition for CEC adjudication of this type of events is needed and proposed. SUMMARY: Background When clinical trials use clinical endpoints, establishing independent Clinical Events Committees (CECs) is recommended to homogenize the interpretation of investigators' data. However, the reproducibility of CEC adjudications is almost unexplored. Objectives To assess the reproducibility of CEC adjudications in a trial of venous thromboembolism (VTE) prevention. Methods The PREVENU trial, a multicenter trial of VTE prevention, included 15 351 hospitalized medical patients. The primary endpoint was the composite of symptomatic VTE, major bleeding or unexplained sudden death (interpreted as possible fatal pulmonary embolism [PE]) at 3 months. The CEC comprised a chairman and four pairs of adjudicators. Of 2970 adjudicated clinical events, a random selection of 179 events (121 deaths, 40 bleeding events, and 18 VTE events) was blindly resubmitted to the CEC. Kappa values and their 95% confidence intervals (CIs) were calculated to measure adjudication agreement. Results Overall, 18 of 179 (10.1%, 95% CI 6.5-15.3%) adjudications proved discordant. Agreement for the PREVENU composite primary endpoint was good (kappa = 0.73, 95% CI 0.61-0.85). When analyzed separately, agreements were very good for non-fatal VTE events (1, 95% CI not applicable), moderate for all (fatal and non-fatal) VTE events (0.58, 95% CI 0.34-0.82), good for fatal and non-fatal major bleeding events (0.71, 95% CI 0.55-0.88), and moderate for all fatal events (0.60, 95% CI 0.40-0.81). Unexplained sudden death interpreted as possible fatal PE was responsible for nine of 18 (50%) discordant adjudications. Conclusion The reproducibility of CEC adjudications was good or very good for non-fatal VTE and bleeding events, but insufficient for VTE-related deaths, for which more precise and widely accepted definitions are needed.

Comparison of the Wells score and the revised Geneva score as a tool to predict pulmonary embolism in outpatients over 65 years of age.The incidence and mortality of pulmonary embolism (PE) is high in the elderly. The Wells score (SW) and the revised Geneva score (RGS) have been validated in patient populations with a large age range. The aim of this study was to compare the predictive accuracy of these two scores in diagnosis of PE in patients over 65 years of age.A prospective multicentre study (nine French and three Belgian centres) was conducted at the same time as the PERCEPIC study. A total of 1757 patients admitted with suspected PE were included and divided into two groups according to age (≥65 years or65 years). The pre-test probability of PE was assessed prospectively for the RGS. The SW was calculated retrospectively. The predictive accuracy of the two scores was compared by the area under the curve (AUC) of the ROC curves.The overall prevalence of PE was 11.3%. The prevalence among patients aged ≥65 in the low, moderate and high pre-test probability groups, evaluated using the WS and was respectively 13.5% (CI 95%: CI 9.9-17.3), 28.2% (CI 22.1-34.3), 50% (CI 26-74) and 8.1% (CI 3.2-12.9), 22.3% (CI 18.2-26.3), 43.7% (CI 25.6-61.9) using the RGS. The AUC for the WS and RGS for patients aged ≥65 was 0.632 (CI 0.574-0.691) and 0.610 (CI 0.555-0.666). The difference between the AUCs was not statistically significant (p = .441).In the population for this study, the WS and RGS have the same PE diagnostic accuracy in patients over age 65. This result should be validated in a prospective study that directly compares these scores.

International audience; BACKGROUND: This study aimed to determine the failure rate of a combination of the PERC and the YEARS rules for the diagnosis of pulmonary embolism (PE) in the emergency department (ED).METHODS: We performed a retrospective analysis of two European cohorts of emergency patients with low gestalt clinical probability of PE (PROPER and PERCEPIC). All patients we included were managed using a conventional strategy (D-dimer test, followed, if positive, by computed tomographic pulmonary angiogram (CTPA). We tested a diagnostic strategy that combined PERC and YEARS to rule out PE. The primary endpoint was a thromboembolic event diagnosed in the ED or at 3-months follow-up. Secondary endpoints included a thromboembolic event at baseline in the ED and a CTPA in the ED. Ninety-five percent confidence intervals (CIs) of proportions were calculated with the use of Wilson's continuity correction.RESULTS: We analyzed 1,951 patients (mean±SD age= 47±18years, 56% women) with an overall proportion of patients with PE of 3.5%. Both PERC and YEARS strategies were associated with 11 missed PE in the ED: failure rate 0.57 (95% CI= 0.32-1.02). At 3-month follow-up, the overall failure rate was 0.83% (95% CI= 0.51-1.35). Among the 503 patients who underwent a CTPA (26%), the use of the PERC-YEARS combination would have ruled out PE without CTPA in 249 patients (50% [95%CI= 45%-54%], absolute reduction13% (95% CI= 11%-14%]).CONCLUSION: The combination of PERC then YEARS was associated with a low risk of PE diagnostic failure and would have resulted in a relative reduction of almost half of CTPA.

BACKGROUND The quick sequential organ failure assessment (qSOFA) score showed good prognostic performance in patients with suspicion of infection in the emergency department (ED). However, previous studies only assessed the performance of individual values of qSOFA during the ED stay. As this score may vary over short timeframes, the optimal time of measurement, and the prognostic value of its variation are unclear. The objective of the present study was to prospectively assess the prognostic value of the change in qSOFA over the first 3 h (ΔqSOFA = qSOFA at 3 h-qSOFA at inclusion). PATIENTS AND METHODS This is an international prospective cohort study conducted in 17 EDs in France, Belgium, and Spain. From November 2016 to March 2017, patients with a suspected infection and a qSOFA score of 2 or higher were included and followed up until death or hospital discharge. qSOFA was measured at inclusion, 1 h and 3 h. Primary end point was in-hospital mortality, truncated at 28 days. RESULTS Of 534 recruited patients, 512 were included in the analysis. The qSOFA was improved at 3 h (ΔqSOFA < 0) in 287 (55%) patients. Overall in-hospital mortality was 27%: 44% when ΔqSOFA greater than 0, 36% when ΔqSOFA = 0, and 18% when ΔqSOFA less than 0. A positive ΔqSOFA was independently associated with reduced in-hospital mortality (adjusted hazard ratio of 0.48, 95% confidence interval: 0.34-0.68). After modeling qSOFA kinetics in the first 3 h, there was a significant difference in adjusted slopes between patients who died and those who survived (0.15, 95% confidence interval: 0.09-0.22, P < 0.001). CONCLUSION In patients with suspected infection presenting to the ED with a qSOFA of 2 or higher, the early change in qSOFA is a strong independent predictor of mortality.

L’embolia polmonare (EP) rimane nel 2014 una sfida per il medico. Dal momento che la patologia e potenzialmente mortale e i segni e i sintomi sono poco specifici, la prima difficolta consiste nel sapere in chi sospettare un’EP e, quindi, in chi iniziare un iter diagnostico. Di fronte a un sospetto di EP, il medico inizia una strategia diagnostica basata su tre elementi principali: la valutazione della probabilita clinica, i D-dimeri e l’angio-TC toracica. La prima fase, la valutazione della probabilita clinica, e la chiave di volta di tutto l’iter diagnostico e terapeutico. Non esiste alcun elemento formale per preferire una metodica di valutazione di probabilita clinica a un’altra. I D-dimeri sono inaffidabili quando la probabilita clinica e forte. Un test di D-dimeri negativo permette di escludere un’EP quando la probabilita clinica e bassa o, per alcune tecniche di dosaggio, quando e bassa o intermedia. L’angio-TC e considerata l’esame di riferimento. Essa ha, tuttavia, dei limiti notevoli, poiche il rischio di errore e aumentato in caso di discordanza tra l’interpretazione della TC e la probabilita clinica. Infine, questa strategia deve essere adattata in contesti particolari (stato di shock, donna gravida, persona anziana, insufficienza renale, ecc.) e fare ricorso ad altre indagini (ecoDoppler venoso, ecocardiografia, scintigrafia, ecc.). Un protocollo che precisi l’iter diagnostico da seguire o, anche, uno strumento informatizzato di aiuto alla decisione migliorano la qualita delle decisioni prese in Pronto Soccorso in occasione di un sospetto di EP.

Introduction Weight loss and fatigue are frequent symptoms as are dysphagia and vomiting. Looking for diagnosis, one would think first about gastric or oesophageal pathology. Combined with abdominal mass, upper abdominal cancer would be a good main hypothesis. We describe here a case of prostatic cancer in a healthy patient showing no urinary symptoms. Case description A 54-year-old man, without medical history, is admitted to the ER for weight loss, fatigue, dysphagia to solids and precocious postprandial vomiting that begun a month ago. Weight loss reaches about 10kg. Clinical examination shows multiple pulseless hard abdominal masses, larger than 5cm and discrete lower limbs oedema. Peripheral pulses are present and symmetrical. Blood analysis reveals severe anemia (Hb 5.6g/dl), kidney failure (creatinine 1.7mg/dl, GFR 40ml.min-1), increase in LDH (400UI/ml) and lactate (4.4mmol/l) levels. Blood transfusion and IV-hydration restore Hb-level to 9.2g/dl but do not correct lactatemia or kidney failure. Abdominal CT (figure 1A-1B) confirms multiple tumors as being retro-peritoneal lymph nodes reaching sizes up to 10cm, along with a bilateral ureterohydronephrosis due to compression. Prostate is irregular and numerous sclerotic bone metastases of the spine are showed. PSA level is 16033g/l (nl Results A prostatic adenocarcinoma is confirmed by lymph node biopsy. Scans (figure 2A-2B) done 40 days after introduction of Degarelix (GnRH antagonist) show a major decrease in tumor volume (>65%). No chemotherapy was initiated due to lack of follow-up from the patient. PSA level is then 40g/l. Anemia stays non-regenerative due to bone marrow involvement. Clinical symptoms resolved.

In patients consulting in the Emergency Department for chest pain, a HEART score ≤ 3 has been shown to rule out an acute coronary syndrome (ACS) with a low risk of major adverse cardiac event (MACE) occurrence. A negative CARE rule (≤ 1) that stands for the first four elements of the HEART score may have similar rule-out reliability without troponin assay requirement. We aim to prospectively assess the performance of the CARE rule and of the HEART score to predict MACE in a chest pain population. Prospective two-center non-interventional study. Patients admitted to the ED for non-traumatic chest pain were included, and followed-up at 6 weeks. The main study endpoint was the 6-week rate of MACE (myocardial infarction, coronary angioplasty, coronary bypass, and sudden unexplained death). 641 patients were included, of whom 9.5% presented a MACE at 6 weeks. The CARE rule was negative for 31.2% of patients, and none presented a MACE during follow-up [0, 95% confidence interval: (0.0-1.9)]. The HEART score was ≤ 3 for 63.0% of patients, and none presented a MACE during follow-up [0% (0.0-0.9)]. With an incidence below 2% in the negative group, the CARE rule seemed able to safely rule out a MACE without any biological test for one-third of patients with chest pain and the HEART score for another third with a single troponin assay.

International audience; IntroductionPERC rule was created to rule out pulmonary embolism (PE) without further exams, with residual PE risk < 2%. Its safety is currently not confirmed in high PE prevalence populations even when combined with low clinical probability assessed by revised Geneva score (RGS). As PERC rule and RGS are 2 similar explicit rules with many redundant criteria, we hypothesized that the combination of PERC rule with gestalt clinical probability could resolve this limitation. Methods We collected prospectively documented clinical gestalt assessments and retrospectively calculated PERC rules and RGS from a prospective study of PE suspected patients. We analyzed performance of combinations of negative PERC with low clinical probability assessed by both methods in high overall PE prevalence population. Results Among the final study population (n = 959), the overall PE prevalence was 29.8%. Seventy-four patients (7.7%) were classified as PERC negative and among them, 4 patients (5.4%) had final diagnosis of PE. When negative PERC was combined with low pretest probability assessed by RGS or gestalt assessment, PE prevalence was respectively 6.2% and 0%. This last combination reaches threshold target of 2% and unnecessary exams could easily have been avoided in this subgroup (6%). However, it confidence interval was still wide (0%; CI 0–5). Conclusions PERC rule combined with low gestalt probability seems to identify a group of patients for whom PE could easily be ruled out without additional test. A larger study is needed to confirm this result and to ensure safety.

Background: Computed tomography pulmonary angiogram (CTPA) has become the standard test in the diagnostic workup of patients with suspected pulmonary embolism (PE). However, young patients may have an increased risk of cancer with CTPA. Perfusion scanning combined with chest X-ray (X/Q) may offer an adequate alternative, but has never been prospectively validated. We directly compared this strategy with CTPA in patients agedMethods: Consecutive patients with a likely clinical probability or an abnormal D-dimer level underwent both CTPA and X/Q. Two trained and experienced nuclear physicians independently analyzed the X/Q-scans. The accuracy of X/Q according to the PISAPED criteria was calculated in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).Results: Seventy-six patients were included, with a PE rate of 33%. The inter-observer agreement for X/Q-scan reading was high (kappa = 0.89). After consensus reading, 21 patients (28%) were categorized as 'PE present', 53 (70%) as 'PE absent', and two (2.6%) as 'non-diagnostic'. In 22%, there was a discrepancy between the X/Q-scan and CPTA for the diagnosis or exclusion of PE. The PPV and NPV were 71% and 83%, respectively.Conclusion: In patients with a high risk of PE, a diagnostic strategy of chest X-ray and perfusion scanning using the PISAPED criteria seems less safe than CTPA. Additional studies should further investigate this diagnostic algorithm. (C) 2015 Elsevier Ltd. All rights reserved.

Pregnancy causes a small increase in risk of venous thromboembolism (VTE), but a large increase in concern upon presentation to an emergency department (ED) with symptoms of pulmonary embolism (PE), which may cause physicians to employ a low test threshold. This was a systematic review with the hypothesis that symptomatic pregnant patients in the ED have a low relative risk (RR) for VTE outcome.Studies in all languages were identified by structured search of PubMed, EMBASE, the Cochrane library, and bibliographies in February 2014. Papers with ED patients evaluated for possible PE that included pregnancy status, and had adequate reference standards, were included. An outcome of VTE (either deep venous thrombosis [DVT] or PE) was considered disease-positive (VTE+). Papers were assessed for selection and publication bias, and heterogeneity (I(2) ). The random effects model was used if I(2) 24%.Seventeen full-length studies of 25,339 patients were analyzed. Pooled data showed I² = 0% with a symmetrical funnel plot. Two small studies with less than 1% of all patients had evidence of selection bias. The frequency of VTE+ rate among the 506 pregnant patients was 4.1% (95% confidence interval [CI] = 2.6% to 6.0%), compared with 12.4% (95% CI = 9.0% to 16.3%) among nonpregnant patients. The pooled RR of pregnancy for VTE+ diagnosis was 0.60 (95% CI = 0.41 to 0.87). Patients in the third trimester had a RR of 0.85 (95% CI = 0.40 to 1.77), and patients of childbearing age (≤45 years) had a RR of 0.56 (95% CI = 0.34 to 0.93).In the ED setting, physicians test for PE in pregnant patients at a low threshold, resulting in a low rate of VTE diagnosis and a RR of VTE that is lower than that for nonpregnant women of childbearing age who are tested for PE in the ED setting.

International audience; Summary: Background: Age-adjusted D-dimer cut-off has recently been proposed to increase D-dimer usefulness in older patients suspected of pulmonary embolism (PE). Objective: We externally validated this age-adjusted D-dimer cut-off using different D-dimer assays in a multicenter sample of emergency department patients. Methods: Secondary analysis of three prospectively collected databases (two European, one American) of patients suspected of having PE. D-dimer performance for ruling out PE was assessed by calculating negative likelihood ratio (nLR) for D-dimer with age-adjusted D-dimer cut-off ( 75 years: NTT halved from 8.1 to 3.6. The proportion of patients over 75 years with normal D-dimer was doubled (27.9% vs. 12.3%). Conclusions: Our study shows that age-adjusted D-dimer had low nLR, allowing its use as a rule-out PE strategy in non-high pretest clinical probability patients, as well as using Vidas(®) , Liatest(®) or MDA(®) assays. This age-adjusted cut-off increased clinical usefulness of D-dimer in older patients. A large prospective study is required to confirm these results.

Study objective: The assessment of clinical probability (as low, moderate, or high) with clinical decision rules has become a cornerstone of diagnostic strategy for patients with suspected pulmonary embolism, but little is known about the use of physician gestalt assessment of clinical probability. We evaluate the performance of gestalt assessment for diagnosing pulmonary embolism. Methods: We conducted a retrospective analysis of a prospective observational cohort of consecutive suspected pulmonary embolism patients in emergency departments. Accuracy of gestalt assessment was compared with the Wells score and the revised Geneva score by the area under the curve (AUC) of receiver operating characteristic curves. Agreement between the 3 methods was determined by κ test. Results: The study population was 1,038 patients, with a pulmonary embolism prevalence of 31.3%. AUC differed significantly between the 3 methods and was 0.81 (95% confidence interval [CI] 0.78 to 0.84) for gestalt assessment, 0.71 (95% CI 0.68 to 0.75) for Wells, and 0.66 (95% CI 0.63 to 0.70) for the revised Geneva score. The proportion of patients categorized as having low clinical probability was statistically higher with gestalt than with revised Geneva score (43% versus 26%; 95% CI for the difference of 17%=13% to 21%). Proportion of patients categorized as having high clinical probability was higher with gestalt than with Wells (24% versus 7%; 95% CI for the difference of 17%=14% to 20%) or revised Geneva score (24% versus 10%; 95% CI for the difference of 15%=13% to 21%). Pulmonary embolism prevalence was significantly lower with gestalt versus clinical decision rules in low clinical probability (7.6% for gestalt versus 13.0% for revised Geneva score and 12.6% for Wells score) and non-high clinical probability groups (18.3% for gestalt versus 29.3% for Wells and 27.4% for revised Geneva score) and was significantly higher with gestalt versus Wells score in high clinical probability groups (72.1% versus 58.1%). Agreement between the 3 methods was poor, with all κ values below 0.3. Conclusion: In our retrospective study, gestalt assessment seems to perform better than clinical decision rules because of better selection of patients with low and high clinical probability.

International audience; Purpose of review: Pulmonary embolism remains one of the leading causes of cardiovascular mortality. The wide range of reported mortality rates reflects heterogeneity in comorbidity and severity of pulmonary embolism. Optimizing risk stratification to prognose pulmonary embolism patients appears to be important to improve management, treatment and clinical outcome.Recent findings: Hemodynamic status is the most important short-term prognostic factor. High-risk pulmonary embolism or massive pulmonary embolism is defined by the patient response more than the clot size: patients with circulatory shock including sustained hypotension should receive thrombolytic therapy in absence of contraindications. Nonmassive or normotensive pulmonary embolism can be further stratified using clinical features, imaging (echocardiography, computed tomography) and biomarkers (troponins, natriuretic peptides): low-risk pulmonary embolism, evaluated by clinical model (Pulmonary Embolism Severity Index; PESI) can potentially be treated as outpatients; and intermediate-risk pulmonary embolism, which can be further stratified into less-severe and more-severe intermediate risk. The last may benefit from intensive clinical surveillance but the risk–benefit ratio for thrombolysis has been inadequately quantified to make any strong recommendation. New anticoagulants may transform traditional pulmonary embolism treatment. Summary: Optimizing risk stratification of patients with normotensive pulmonary embolism before they develop overt hemodynamic instability is the challenge of current pulmonary embolism management. Treatment strategy has to integrate this risk stratification and new anticoagulants arrival.

International audience; Background:If the prevalence of pulmonary embolism (PE) differs significantly between the US and Europe, this observation could reduce the generalizability of diagnostic protocols for PE derived in either location.Objective:To determine possible causes and potential clinical consequences of these PE prevalence differences.Methods:Secondary analysis of three prospectively collected multicenter samples (two French and one from the US) including 3174 European and 7940 American PE-suspected patients in Emergency departments (ED) (117 for Europe and 12 for US). Comparison of clinical features, resource use and outcomes of European- and US-suspected PE populations in ED.Results:European patients evaluated for PE were significantly older and had a higher clinical pretest probability (CPP) for PE. The final PE prevalence was significantly higher in Europe, in the overall sample (26.5% vs. 7.6%) and in each level of CPP. Suspected European patients categorized as low CPP had a higher posttest probability than US low CPP patients. Suspected US patients categorized as high CPP had a much lower posttest probability of PE than in Europe. The mean number of tests performed for one PE diagnosis was lower in Europe (7.4 vs. 21.6). Among patients diagnosed with PE, European patients had a higher mean severity of illness score and a higher PE-mortality rate (3.4% vs. 0.7%).Conclusions:Among patients suspected of a PE and those ultimately diagnosed with a PE, European patients had higher acuity, a higher pretest probability and worse outcome than US patients. The present study underscores the importance of disease prevalence for pretest probability scoring approaches and for significance interpretation of imaging tests.

International audience; BackgroundClinical guidelines recommend risk stratification of patients with acute pulmonary embolism (PE). Active cancer increases risk of PE and worsens prognosis, but also causes incidental PE that may be discovered during cancer staging. No quantitative decision instrument has been derived specifically for patients with active cancer and PE. Methods Classification and regression technique was used to reduce 25 variables prospectively collected from 408 patients with AC and PE. Selected variables were transformed into a logistic regression model, termed POMPE-C, and compared with the pulmonary embolism severity index (PESI) score to predict the outcome variable of death within 30 days. Validation was performed in an independent sample of 182 patients with active cancer and PE. Results POMPE-C included eight predictors: body mass, heart rate > 100, respiratory rate, SaO2%, respiratory distress, altered mental status, do not resuscitate status, and unilateral limb swelling. In the derivation set, the area under the ROC curve for POMPE-C was 0.84 (95% CI: 0.82-0.87), significantly greater than PESI (0.68, 0.60-0.76). In the validation sample, POMPE-C had an AUC of 0.86 (0.78-0.93). No patient with POMPE-C estimate ≤ 5% died within 30 days (0/50, 0-7%), whereas 10/13 (77%, 46-95%) with POMPE-C estimate > 50% died within 30 days. Conclusion In patients with active cancer and PE, POMPE-C demonstrated good prognostic accuracy for 30 day mortality and better performance than PESI. If validated in a large sample, POMPE-C may provide a quantitative basis to decide treatment options for PE discovered during cancer staging and with advanced cancer.

INTRODUCTION: The Wells score is widely used in the assessment of pretest probability of pulmonary embolism (PE). The revised Geneva score is a fully standardized clinical decision rule that was recently validated and further simplified. We compared the predictive accuracy of these two scores. METHODS: Data from 339 patients clinically suspected of PE from two prospective management studies were used and combined. Pretest probability of PE was assessed prospectively by the Wells score. The simplified revised (SR) Geneva score was calculated retrospectively. The predictive accuracy of both scores was compared by area under the curve (AUC) of receiver operating characteristic (ROC) curves. RESULTS: The overall prevalence of PE was 19%. Prevalence of PE in the low, moderate and high pretest probability groups assessed by the Wells score and by the simplified revised Geneva score was respectively 2%(95% CI (CI) 1-6) and 4% (CI 2-10), 28% (CI 22-35) and 25% (CI 20-32), 93% (CI 70-99) and 56% (CI 27-81). The Wells score performed better than the simplified revised Geneva score in patients with a high suspicion of PE (p

The major potential adverse effect of use of sulfonylurea agents (SUAs) is a hyperinsulinaemic state that causes hypoglycaemia. It may be observed during chronic therapeutic dosing, even with very low doses of a SUA, and especially in older patients. It may also result from accidental or intentional poisoning in both diabetic and nondiabetic patients. The traditional approach to SUA-induced hypoglycaemia includes administration of glucose, and glucagon or diazoxide in those who remain hypoglycaemic despite repeated or continuous glucose supplementation. However, these antidotal approaches are associated with several shortcomings, including further exacerbation of insulin release by glucose and glucagon, leading only to a temporary beneficial effect and later relapse into hypoglycaemia, as well as the adverse effects of both glucagon and diazoxide. Octreotide inhibits the secretion of several neuropeptides, including insulin, and has successfully been used to control life-threatening hypoglycaemia caused by insulinoma or persistent hyperinsulinaemic hypoglycaemia of infancy. Therefore, this agent should in theory also be useful to decrease glucose requirements and the number of hypoglycaemic episodes in patients with SUA-induced hypoglycaemia. This has apparently been confirmed by experimental data, one retrospective study based on chart review, and several anecdotal case reports. There is thus a need for further prospective studies, which should be adequately powered, randomized and controlled, to confirm the probable beneficial effect of octreotide in this setting.

Pyridoxine (vitamin B6) is a co-factor in many enzymatic pathways involved in amino acid metabolism: the main biologically active form is pyridoxal 5-phosphate. Pyridoxine has been used as an antidote in acute intoxications, including isoniazid overdose, Gyromitra mushroom or false morrel (monomethylhydrazine) poisoning and hydrazine exposure. It is also recommended as a co-factor to improve the conversion of glyoxylic acid into glycine in ethylene glycol poisoning. Other indications are recommended by some sources (for example crimidine poisoning, zipeprol and theophylline-induced seizures, adjunct to d-penicillamine chelation), without significant supporting data. The value of pyridoxine or its congener metadoxine as an agent for hastening ethanol metabolism or improving vigilance in acute alcohol intoxication is controversial. This paper reviews the various indications of pyridoxine in clinical toxicology and the supporting literature. The potential adverse effects of excessive pyridoxine dosage will also be summarized.

The recreational abuse of toxic substances is an increasing problem and is now a frequent source of emergency department visits in most developed countries, especially at night and during weekends [1, 2]. Among the wide variety of compounds that are observed, special attention must be paid to the ‘club drugs’.

Mondor disease is a form of superficial thrombophlebitis affecting the subcutaneous veins, specifically of the anterolateral thoracoabdominal wall. Clinical presentation is commonly a subcutaneous, tender, painful cordlike induration, usually founded in the breast or axilla. It affects typically middle-aged women. A 36-year-old patient was admitted to the emergency department to a chest discomfort and to discovery of a palpable, nonerythematous, and painful cordlike structure running from the inferior pole of her left breast to the left iliac pit. She had no history of trauma, injury, or intensive physical activity. Ultrasonography confirmed thrombosis of the thoracoepigastric vein. A thrombophilic workup performed 2 years ago was normal. The patient was treated by enoxaparin 1 mg/kg per day for 30 days. Evolution was favorable. The etiology of Mondor disease remains unclear. Predisposing factors are mainly trauma, excessive physical activity, surgery, infections. Ultrasonography is used to confirm the diagnosis. Coagulation tests should be performed to exclude hypercoagulability condition. In the past, symptomatic approach with anti-inflammatory drugs was proposed. Recent guidelines suggest prophylactic or intermediate doses of low-molecular-weight heparin for at least 4 weeks. Although uncommon, Mondor disease has to be recognized to avoid useless diagnosis testing and to deliver a specific treatment.

article Introduction: PERC rule was created to rule out pulmonary embolism (PE) without further exams, with resid- ual PE riskb2%. Its safety is currently not con! rmed in high PE prevalence populations even when combined with low clinical probability assessed by revised Geneva score (RGS). As PERC rule and RGS are 2 similar ex- plicit rules with many redundant criteria, we hypothesized that the combination of PERC rule with gestalt clinical probability could resolve this limitation. Methods: We collected prospectively documented clinical gestalt assessments and retrospectively calculated PERC rules and RGS from a prospective study of PE suspected patients. We analyzed performance of combi- nations of negative PERC with low clinical probability assessed by both methods in high overall PE prevalence

Hyperinsulinaemia/euglycaemia therapy (HIET) consists of the infusion of high-dose regular insulin (usually 0.5 to 1 IU/kg per hour) combined with glucose to maintain euglycaemia. HIET has been proposed as an adjunctive approach in the management of overdose of calcium-channel blockers (CCBs). Indeed, experimental data and clinical experience, although limited, suggest that it could be superior to conventional pharmacological treatments including calcium salts, adrenaline (epinephrine) or glucagon. This paper reviews the patho-physiological principles underlying HIET. Insulin administration seems to allow the switch of the cell metabolism from fatty acids to carbohydrates that is required in stress conditions, especially in the myocardium and vascular smooth muscle, resulting in an improvement in cardiac contractility and restored peripheral resistances. Studies in experimental verapamil poisoning in dogs have shown that HIET significantly improves metabolism, haemodynamics and survival in comparison with conventional therapies. Clinical experience currently consists only of a few isolated cases or short series in which the administration of HIET substantially improved cardiovascular conditions in life-threatening CCB poisonings, allowing the progressive discontinuation of vasoactive agents. While we await further well-designed clinical trials, some rational recommendations are made about the use of HIET in severe CBB overdose. Although the mechanism of action is less well understood in this condition, some experimental data suggesting a potential benefit of HIET in β-adrenergic blocker toxicity are discussed; clinical data are currently lacking.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well tolerated, but rare serious complications may occur in some patients receiving VPA chronically, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity (VHT) and VPA-induced hyperammonaemic encephalopathy (VHE). Some data suggest that VHT and VHE may be promoted by carnitine deficiency. Acute VPA intoxication also occurs as a consequence of intentional or accidental overdose and its incidence is increasing, because of use of VPA in psychiatric disorders. Although it usually results in mild central nervous system depression, serious toxicity and even fatal cases have been reported. Several studies or isolated clinical observations have suggested the potential value of oral L-carnitine in reversing carnitine deficiency or preventing its development as well as some adverse effects due to VPA. Carnitine supplementation during VPA therapy in high-risk patients is now recommended by some scientific committees and textbooks, especially paediatricians. L-carnitine therapy could also be valuable in those patients who develop VHT or VHE. A few isolated observations also suggest that L-carnitine may be useful in patients with coma or in preventing hepatic dysfunction after acute VPA overdose. However, these issues deserve further investigation in controlled, randomized and probably multicentre trials to evaluate the clinical value and the appropriate dosage of L-carnitine in each of these conditions.

The major potential adverse effect of use of sulfonylurea agents (SUAs) is a hyperinsulinaemic state that causes hypoglycaemia. It may be observed during chronic therapeutic dosing, even with very low doses of a SUA, and especially in older patients. It may also result from accidental or intentional poisoning in both diabetic and nondiabetic patients. The traditional approach to SUA-induced hypoglycaemia includes administration of glucose, and glucagon or diazoxide in those who remain hypoglycaemic despite repeated or continuous glucose supplementation. However, these antidotal approaches are associated with several shortcomings, including further exacerbation of insulin release by glucose and glucagon, leading only to a temporary beneficial effect and later relapse into hypoglycaemia, as well as the adverse effects of both glucagon and diazoxide. Octreotide inhibits the secretion of several neuropeptides, including insulin, and has successfully been used to control life-threatening hypoglycaemia caused by insulinoma or persistent hyperinsulinaemic hypoglycaemia of infancy. Therefore, this agent should in theory also be useful to decrease glucose requirements and the number of hypoglycaemic episodes in patients with SUA-induced hypoglycaemia. This has apparently been confirmed by experimental data, one retrospective study based on chart review, and several anecdotal case reports. There is thus a need for further prospective studies, which should be adequately powered, randomized and controlled, to confirm the probable beneficial effect of octreotide in this setting.