S100B vs. "GFAP and UCH-L1" assays in the management of mTBI patients.

OBJECTIVES: To compare for the first time the performance of "GFAP and UCH-L1" vs. S100B in a cohort of patients managed for mild traumatic brain injury (mTBI) according to actualized French guidelines. METHODS: A prospective study was recently carried at the Emergency Department of Clermont-Ferrand University Hospital in France. Patients with mTBI presenting a medium risk of complications were enrolled. Blood S100B and "GFAP and UCHL-1" were sampled and measured according to French guidelines. S100B was measured in patients with samples within 3 h of trauma (Cobas®, Roche Diagnostics), while GFAP and UCHL-1 were measured in all patients (samples <3 h and 3-12 h) using another automated assay (i-STAT® Alinity, Abbott). RESULTS: For sampling <3 h, serum S100B correctly identifies intracranial lesions with a specificity of 25.7 % (95 % CI; 19.5-32.6 %), a sensitivity of 100 % (95 % CI; 66.4-100 %), and a negative predictive value of 100 % (95 % CI; 92.5-100 %). For sampling <12 h, plasma "GFAP and UCH-L1" levels correctly identify intracranial lesions with a specificity of 31.7 % (95 % CI; 25.7-38.2 %), a sensitivity of 100 % (95 % CI; 73.5-100 %), and a negative predictive value of 100 % (95 % CI; 95-100 %). Comparison of specificities (25.7 vs. 31.7 %) did not reveal a statistically significant difference (p=0.16). CONCLUSIONS: We highlight the usefulness of measuring plasma "GFAP and UCH-L1" levels to target mTBI patients (sampling within 12 h post-injury) and optimize the reduction of CT scans.

Derivation and validation of a clinical prediction rule for thrombolysis-associated major bleeding in patients with acute pulmonary embolism: the BACS score.

BACKGROUND: Improved prediction of the risk of major bleeding in patients with acute pulmonary embolism (PE) receiving systemic thrombolysis is crucial to guide the choice of therapy. METHODS: The study included consecutive patients with acute PE who received systemic thrombolysis in the RIETE registry. We used multivariable logistic regression analysis to create a risk score to predict 30-day major bleeding episodes. We externally validated the risk score in patients from the COMMAND VTE registry. We also compared the newly created risk score against the Kuijer and RIETE scores. RESULTS: Multivariable logistic regression identified four predictors for major bleeding: recent major Bleeding (3 points), Age >75 years (1 point), active Cancer (1 point), and Syncope (1 point) (BACS). Among 1172 patients receiving thrombolytic therapy in RIETE, 446 (38%) were classified as having low-risk (none of the variables present, 0 points) of major bleeding according to the BACS score, and the overall 30-day major bleeding rate of this group was 2.9% (95% CI, 1.6-4.9%), compared with 44% (95% CI, 14-79%) in the high-risk group (>3 points). In the validation cohort, 51% (149/290) of patients were classified as having low-risk, and the overall 30-day major bleeding rate of this group was 1.3%. In RIETE, the 30-day major bleeding event rates in the Kuijer and RIETE low-risk stratum were 5.3% and 4.4%, respectively. CONCLUSIONS: The BACS score is an easily applicable aid for prediction of the risk of major bleeding in the population of PE patients who receive systemic thrombolysis.

Guideline-Based Clinical Assessment Versus Procalcitonin-Guided Antibiotic Use in Pneumonia: A Pragmatic Randomized Trial.

STUDY OBJECTIVE: Efforts to reduce unnecessary and unnecessarily long antibiotic treatment for community-acquired pneumonia have been attempted through use of procalcitonin and through guidelines based on serial clinical assessment. Our aim is to compare guideline-based clinical assessment- and procalcitonin algorithm-guided antibiotic use among patients with community-acquired pneumonia. METHODS: We performed a pragmatic, randomized, multicenter trial from November 2012 to April 2015 at 12 French hospitals. We included emergency department (ED) patients older than 18 years with community-acquired pneumonia. Patients were randomly assigned to either the procalcitonin-guided or clinical assessment group. In accordance with past studies, we hypothesized that serial clinical assessment would be superior to procalcitonin-guided care. The primary outcome was antibiotic duration, and secondary outcomes included rates of antibiotic duration less than or equal to 5 days, and clinical success and combined serious adverse outcomes at 30 days in the intention-to-treat population. RESULTS: Of 370 eligible patients, 285 (77%) were randomly assigned to either clinical assessment- (n=143) or procalcitonin-guided care (n=142). Median age was 67 years (range 18 to 93 years) and 40% of patients were deemed to have Pneumonia Severity Index class IV or V. Procalcitonin algorithm adherence was 76%. Antibiotic duration was not significantly different between clinical assessment- and procalcitonin-guided groups (median 9 versus 10 days, respectively). Clinical success rate was 92% in each group and serious adverse outcome rates were similar (15% versus 20%, respectively). CONCLUSION: Guideline-based serial clinical assessment did not reduce antibiotic exposure compared with procalcitonin-guided care among ED patients with community-acquired pneumonia. The strategies were similar in terms of duration of antibiotic use and clinical outcomes.

Clinical validation of S100B in the management of a mild traumatic brain injury: issues from an interventional cohort of 1449 adult patients.

BACKGROUND: This study's primary objective was to validate the routine use of S100B via a prospective study. The aim was a reduction of cranial computed tomography (CCT) scans by 30%. The secondary goal was to investigate the influence of age and associated risk factors on the reduction of CCT. METHODS: S100B (sampling within 3 h postinjury) was used for patients with mild traumatic brain injury (mTBIs) presenting a medium risk of complications and requiring a CCT scan. Patients with negative S100B (S100B-) were discharged without a CCT scan. RESULTS: Of the 1449 patients included in this study, 468 (32.3%) had S100B- with a sensitivity of 96.4% (95% CI: 87.5%-99.6%), a specificity of 33.4% (95% CI: 31%-36%) and a negative predictive value of 99.6% (95% CI: 98.5%-99.9%). No significant difference in serum levels or the S100B+ rate was observed if patients had retrograde amnesia (0.16 µg/L; 63.8%), loss of consciousness (0.13; 63.6%) or antiplatelet therapy (0.20; 77.9%). Significant differences were found between the S100B concentrations and S100B positivity rates in patients >65 years old and all the groups with patients <55 years old (18-25, 26-35, 36-45 and 46-55). From 18 to 65 years old (n=874), the specificity is 39.3% (95% CI: 36%-42.6%) compared to 18.7% (95% CI: 15.3%-22.3%) for patients >65 years old (n=504). CONCLUSIONS: The clinical use of S100B in mTBI management reduces the use of CCTs by approximately one-third; furthermore, the percentage of CCTs reduction is influenced by the age of the patient.

Maximal tachycardia and high cardiac strain during night shifts of emergency physicians.

PURPOSE: To compare tachycardia and cardiac strain between 24-hour shifts (24hS) and 14-hour night shifts (14hS) in emergency physicians (EPs), and to investigate key factors influencing tachycardia and cardiac strain. METHODS: We monitored heart rate (HR) with Holter-ECG in a shift-randomized trial comparing a 24hS, a 14hS, and a control day, within a potential for 19 EPs. We also measured 24-h HR the third day (D3) after both shifts. We measured perceived stress by visual analog scale and the number of life-and-death emergencies. RESULTS: The 17 EPs completing the whole protocol reached maximal HR (180.9 ± 6.9 bpm) during both shifts. Minutes of tachycardia >100 bpm were higher in 24hS (208.3 ± 63.8) than in any other days (14hS: 142.3 ± 36.9; D3/14hS: 64.8 ± 31.4; D3/24hS: 57.6 ± 19.1; control day: 39.2 ± 11.6 min, p < .05). Shifts induced a cardiac strain twice higher than in days not involving patients contact. Each life-and-death emergency enhanced 26 min of tachycardia ≥100 bpm (p < .001), 7 min ≥ 110 bpm (p < .001), 2 min ≥ 120 bpm (p < .001) and 19 min of cardiac strain ≥30% (p = .014). Stress was associated with greater duration of tachycardia ≥100, 110 and 120 bpm, and of cardiac strain ≥30% (p < .001). CONCLUSION: We demonstrated several incidences of maximal HR during shifts combined with a high cardiac strain. Duration of tachycardia were the highest in 24hS and lasted several hours. Such values are comparable to those of workers exposed to high physical demanding tasks or heat. Therefore, we suggest that EPs limit their exposure to 24hS. We, furthermore, demonstrated benefits of HR monitoring for identifying stressful events. ClinicalTrials.gov identifier: NCT01874704.

Intervention Study with Algoplus® : A Pain Behavioral Scale for Older Patients in the Emergency Department.

OBJECTIVES: Evaluation of acute pain is often difficult in older patients admitted to the Emergency Department (ED), and self-evaluation of pain is not always possible. This observational study evaluates how the systematic use of Algoplus® , a validated behavioral scale, could improve pain management of older persons admitted to the ED. METHOD: The intervention study (NCT 02258503) took place in 4 steps in the ED, University Hospital Clermont-Ferrand, France. Pain assessment and analgesics prescription were collected from medical files for 3 months. For 6 months, the whole staff of the ED were trained on pain assessment and to use Algoplus® scale (3-same as step 1). To evaluate the intervention, pain assessment and analgesics prescription were compared before and after implementation by 2-sided tests with a type I error set at α = 0.05. RESULTS: The intervention led to systematic pain evaluation with Algoplus® in 100% of patients (≥ 75 years old, n = 434) and was completed by numeric rating scale (NRS) and other evaluations. Pearson's correlation between NRS ≥ 3 and Algoplus® < 2 was 0.61. Prescription of analgesics (+6%) especially opioids increased nonsignificantly but was similar for all patients whatever the evaluation. CONCLUSIONS: The systematic introduction of Algoplus® scale in the ED allowed a change in practice by improving evaluation and management of pain in patients ≥ 75 years old, especially when difficult to be evaluated. Algoplus® allowed an objective levelling of analgesics prescription in all admitted patients. It also promoted field action to improve pain management in ED.

Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study.

IMPORTANCE: D-dimer measurement is an important step in the diagnostic strategy of clinically suspected acute pulmonary embolism (PE), but its clinical usefulness is limited in elderly patients. OBJECTIVE: To prospectively validate whether an age-adjusted D-dimer cutoff, defined as age × 10 in patients 50 years or older, is associated with an increased diagnostic yield of D-dimer in elderly patients with suspected PE. DESIGN, SETTINGS, AND PATIENTS: A multicenter, multinational, prospective management outcome study in 19 centers in Belgium, France, the Netherlands, and Switzerland between January 1, 2010, and February 28, 2013. INTERVENTIONS: All consecutive outpatients who presented to the emergency department with clinically suspected PE were assessed by a sequential diagnostic strategy based on the clinical probability assessed using either the simplified, revised Geneva score or the 2-level Wells score for PE; highly sensitive D-dimer measurement; and computed tomography pulmonary angiography (CTPA). Patients with a D-dimer value between the conventional cutoff of 500 µg/L and their age-adjusted cutoff did not undergo CTPA and were left untreated and formally followed-up for a 3-month period. MAIN OUTCOMES AND MEASURES: The primary outcome was the failure rate of the diagnostic strategy, defined as adjudicated thromboembolic events during the 3-month follow-up period among patients not treated with anticoagulants on the basis of a negative age-adjusted D-dimer cutoff result. RESULTS: Of the 3346 patients with suspected PE included, the prevalence of PE was 19%. Among the 2898 patients with a nonhigh or an unlikely clinical probability, 817 patients (28.2%) had a D-dimer level lower than 500 µg/L (95% CI, 26.6%-29.9%) and 337 patients (11.6%) had a D-dimer between 500 µg/L and their age-adjusted cutoff (95% CI, 10.5%-12.9%). The 3-month failure rate in patients with a D-dimer level higher than 500 µg/L but below the age-adjusted cutoff was 1 of 331 patients (0.3% [95% CI, 0.1%-1.7%]). Among the 766 patients 75 years or older, of whom 673 had a nonhigh clinical probability, using the age-adjusted cutoff instead of the 500 µg/L cutoff increased the proportion of patients in whom PE could be excluded on the basis of D-dimer from 43 of 673 patients (6.4% [95% CI, 4.8%-8.5%) to 200 of 673 patients (29.7% [95% CI, 26.4%-33.3%), without any additional false-negative findings. CONCLUSIONS AND RELEVANCE: Compared with a fixed D-dimer cutoff of 500 µg/L, the combination of pretest clinical probability assessment with age-adjusted D-dimer cutoff was associated with a larger number of patients in whom PE could be considered ruled out with a low likelihood of subsequent clinical venous thromboembolism. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01134068.

Management of cancer-associated thromboembolism in vulnerable population.

Although all patients with cancer-associated thrombosis (CAT) have a high morbidity and mortality risk, certain groups of patients are particularly vulnerable. This may expose the patient to an increased risk of thrombotic recurrence or bleeding (or both), as the benefit-risk ratio of anticoagulant treatment may be modified. Treatment thus needs to be chosen with care. Such vulnerable groups include older patients, patients with renal impairment or thrombocytopenia, and underweight and obese patients. However, these patient groups are poorly represented in clinical trials, limiting the available data, on which treatment decisions can be based. Meta-analysis of data from randomised clinical trials suggests that the relative treatment effect of direct oral factor Xa inhibitors (DXIs) and low molecular weight heparin (LMWH) with respect to major bleeding could be affected by advanced age. No evidence was obtained for a change in the relative risk-benefit profile of DXIs compared to LMWH in patients with renal impairment or of low body weight. The available, albeit limited, data do not support restricting the use of DXIs in patients with CAT on the basis of renal impairment or low body weight. In older patients, age is not itself a critical factor for choice of treatment, but frailty is such a factor. Patients over 70 years of age with CAT should undergo a systematic frailty evaluation before choosing treatment and modifiable bleeding risk factors should be addressed. In patients with renal impairment, creatine clearance should be assessed and monitored regularly thereafter. In patients with an eGFR<30mL/min/1.72m2, the anticoagulant treatment may need to be adapted. Similarly, platelet count should be assessed prior to treatment and monitored regularly. In patients with grade 3-4, thrombocytopenia (<50,000 platelets/µL) treatment with a LMWH at a reduced dose should be considered. For patients with CAT and low body weight, standard anticoagulant treatment recommendations are appropriate, whereas in obese patients, apixaban may be preferred.

Home treatment for patients with cancer-associated venous thromboembolism.

Patients hospitalised with acute venous thromboembolism (VTE), and notably patients with pulmonary embolism, often remain in hospital for extended periods due to the perceived risk of complications. However, several studies have shown that home treatment of selected patients is feasible and safe, with a low incidence of adverse events. This may offer clear benefits for patients' quality of life, hospital planning and cost to the health service. Nonetheless, there is a need for a VTE risk-stratification tool specifically addressing prognosis in patients with cancer. This may aid in the selection of low-risk patients with cancer and VTE who are suitable for outpatient treatment. Although several prognostic scores have been proposed, we suggest using a pragmatic clinical decision-making tool such as the Hestia criteria for selecting patients for home care in everyday clinical practice. Once patients have been discharged, it is mandatory to monitor patients regularly (we suggest after 3 days, 10 days, 1 month and 3 months, or more frequently if needed) with the involvement of a multidisciplinary team, so that appropriate and timely remedial action can be taken in case of warning signs of complications. If patients are selected carefully and monitored effectively, many patients who experience acute VTE can be cared for safely at home.

Consensus paper on the assessment of adult patients with traumatic brain injury with Glasgow Coma Scale 13-15 at the emergency department: A multidisciplinary overview.

Traumatic brain injury (TBI) is a common reason for presenting to emergency departments (EDs). The assessment of these patients is frequently hampered by various confounders, and diagnostics is still often based on nonspecific clinical signs. Throughout Europe, there is wide variation in clinical practices, including the follow-up of those discharged from the ED. The objective is to present a practical recommendation for the assessment of adult patients with an acute TBI, focusing on milder cases not requiring in-hospital care. The aim is to advise on and harmonize practices for European settings. A multiprofessional expert panel, giving consensus recommendations based on recent scientific literature and clinical practices, is employed. The focus is on patients with a preserved consciousness (Glasgow Coma Scale 13-15) not requiring in-hospital care after ED assessment. The main results of this paper contain practical, clinically usable recommendations for acute clinical assessment, decision-making on acute head computerized tomography (CT), use of biomarkers, discharge options, and needs for follow-up, as well as a discussion of the main features and risk factors for prolonged recovery. In conclusion, this consensus paper provides a practical stepwise approach for the clinical assessment of patients with an acute TBI at the ED. Recommendations are given for the performance of acute head CT, use of brain biomarkers and disposition after ED care including careful patient information and organization of follow-up for those discharged.

[Translation into French and republication of: "Home treatment for patients with cancer-associated venous thromboembolism"]. / Traduction et republication de : « Traitement à domicile des patients atteints de maladie veineuse thromboembolique associée au cancer ¼.

Patients hospitalised with acute venous thromboembolism (VTE), and notably patients with pulmonary embolism, often remain in hospital for extended periods due to the perceived risk of complications. However, several studies have shown that home treatment of selected patients is feasible and safe, with a low incidence of adverse events. This may offer clear benefits for patients' quality of life, hospital planning and cost to the health service. Nonetheless, there is a need for a VTE risk-stratification tool specifically addressing prognosis in patients with cancer. This may aid in the selection of low-risk patients with cancer and VTE who are suitable for outpatient treatment. Although several prognostic scores have been proposed, we suggest using a pragmatic clinical decision-making tool such as the Hestia criteria for selecting patients for home care in everyday clinical practice. Once patients have been discharged, it is mandatory to monitor patients regularly (we suggest after 3 days, 10 days, 1 month and 3 months, or more frequently if needed) with the involvement of a multidisciplinary team, so that appropriate and timely remedial action can be taken in case of warning signs of complications. If patients are selected carefully and monitored effectively, many patients who experience acute VTE can be cared for safely at home.

Statin use and mortality in patients with deep vein thrombosis. Data from the RIETE Registry.

BACKGROUND: The association between statin use and mortality in patients with deep vein thrombosis (DVT) has not been rigorously evaluated. METHODS: We used the data in the RIETE registry to examine the association between statin use and mortality at 3 months. We used mixed effects survival models accounting for clinical covariates and clustering of patients in enrolling centers. RESULTS: From January 2009 through April 2022, there were 46,440 patients with isolated DVT in RIETE (in the lower-limbs 42,291, in the upper limbs 4149). Of these, 21 % and 18 %, respectively, were using statins. Statin users were older than non-users (72 ± 12 vs. 62 ± 18 years), and more likely had diabetes, hypertension, prior myocardial infarction or ischemic stroke, or were receiving antiplatelets. The 3-month mortality rates were: 6.0 % vs. 5.8 %, respectively. On multilevel multivariable analysis, the adjusted hazard ratio (aHR) for all-cause death in statin users vs. non-users was 0.77 (95%CI: 0.69-0.86). The 3-month risk of death in statin users was significantly lower than in non-users in patients with upper-limb DVT (aHR: 0.81; 95%CI: 0.72-0.91), distal lower-limb DVT (aHR: 0.48; 95%CI: 0.32-0.72), or proximal lower-limb DVT (aHR: 0.69; 95%CI: 0.50-0.95), and in those receiving simvastatin (aHR: 0.73; 95%CI: 0.60-0.90), atorvastatin (aHR: 0.70; 95%CI: 0.59-0.85), or rosuvastatin (aHR: 0.47; 95%CI: 0.27-0.80). Major bleeding, used as a falsification endpoint, did not show an association with use of statins at 3-month follow-up. CONCLUSIONS: Statin users with isolated DVT were at significantly lower risk for death at 3 months than non-users.

Risk of recurrence after discontinuing anticoagulation in patients with COVID-19- associated venous thromboembolism: a prospective multicentre cohort study.

Background: The clinical relevance of recurrent venous thromboembolism (VTE) after discontinuing anticoagulation in patients with COVID-19-associated VTE remains uncertain. We estimated the incidence rates and mortality of VTE recurrences developing after discontinuing anticoagulation in patients with COVID-19-associated VTE. Methods: A prospective, multicenter, non-interventional study was conducted between March 25, 2020, and July 26, 2023, including patients who had discontinued anticoagulation after at least 3 months of therapy. All patients from the registry were analyzed during the study period to verify inclusion criteria. Patients with superficial vein thrombosis, those who did not receive at least 3 months of anticoagulant therapy, and those who were followed for less than 15 days after discontinuing anticoagulation were excluded. Outcomes were: 1) Incidence rates of symptomatic VTE recurrences, and 2) fatal PE. The rate of VTE recurrences was defined as the number of patients with recurrent VTE divided by the patient-years at risk of recurrent VTE during the period when anticoagulation was discontinued. Findings: Among 1106 patients with COVID-19-associated VTE (age 62.3 ± 14.4 years; 62.9% male) followed-up for 12.5 months (p25-75, 6.3-20.1) after discontinuing anticoagulation, there were 38 VTE recurrences (3.5%, 95% confidence interval [CI]: 2.5-4.7%), with a rate of 3.1 per 100 patient-years (95% CI: 2.2-4.2). No patient died of recurrent PE (0%, 95% CI: 0-7.6%). Subgroup analyses showed that patients with diagnosis in 2021-2022 (vs. 2020) (Hazard ratio [HR] 2.86; 95% CI 1.45-5.68) or those with isolated deep vein thrombosis (vs. pulmonary embolism) (HR 2.31; 95% CI 1.19-4.49) had significantly higher rates of VTE recurrences. Interpretation: In patients with COVID-19-associated VTE who discontinued anticoagulation after at least 3 months of treatment, the incidence rate of recurrent VTE and the case-fatality rate was low. Therefore, it conceivable that long-term anticoagulation may not be required for many patients with COVID-19-associated VTE, although further research is needed to confirm these findings. Funding: Sanofi and Rovi, Sanofi Spain.

Usefulness of nefopam in treating pain of severe uncomplicated renal colics in adults admitted to emergency units: a randomised double-blind controlled trial. The 'INCoNU' study.

BACKGROUND: Renal colic pain is a frequent cause of emergency department admissions (1-2% of admissions). It is extremely painful, often requiring intravenous morphine titration. The aim of this study was to estimate the effect of adding nefopam to ketoprofen upon subsequent morphine consumption and the time needed to achieve adequate analgesia in renal colic. METHODS: The authors undertook a prospective, monocentric, randomised, double-blind, placebo-controlled, parallel-group study, using an intent-to-treat analysis. Patients admitted to the emergency department for suspected hyperalgesic (evaluated with a visual analogue scale (VAS)) renal colic were enrolled in the study. They were administered an initial treatment of ketoprofen before being randomly assigned to either the placebo or nefopam group. RESULTS: Thirty patients admitted to the emergency department were enrolled in the study. Morphine analgesia was necessary for 10 patients (66.6%) (95% CI 40% to 90%) in the nefopam group and 8 (53.3%) (95% CI 30% to 80%) in the placebo group, with no statistically significant difference found (difference 13.3%, 95% CI -51% to 24%). The time needed to achieve adequate analgesia in the case of morphine titration was 8.3 min (95% CI 4.2 to 12.5) in the nefopam group and 9 min (95% CI 2.7 to 15.3) in the placebo group, with no statistically significant difference (difference 0.7, 95% CI 7.25 to 8.58). CONCLUSION: This study did not reveal any significant difference between nefopam and placebo. This may be due to lack of statistical power or lack of effectiveness. CLINICAL TRIAL REGISTRATION NUMBER: http://ClinicalTrials.gov ID number NCT00639574.

Thrombin generation in real life bleeding patients on oral anticoagulants reversed (or not) with (activated) prothrombin complex concentrate.

BACKGROUND: Bleeding during oral anticoagulant therapy is currently codified by expert guidelines. Monitoring of coagulation during bleeding events is challenging. Our study sought to assess thrombin generation assay (TGA) in direct oral anticoagulant-treated patients without bleeding (WB), bleeding without reversal therapy (BR-), and bleeding with reversal therapy (BR+). METHODS: We conducted a prospective, monocentric study from June 2015 to June 2018. For all bleeding groups, TGA was evaluated using platelet-poor plasma collected upon arrival at emergency (T0), and 30 min (T1), 6 h (T2) and 24 h (T3) after reversal therapy (if indicated) following activation by tissue factor 5 pM and phospholipids. RESULTS: Overall, 292 patients participated, including 91 BR+, 94 BR-, and 107 WB patients. At T0, vitamin K antagonist reversed (VKA-BR+) patients experienced a significant decrease in TGA parameters (ETP and peak) compared with VKA without bleeding (VKA-WB). Compared with healthy controls, VKA-BR+ patients reversed by four-factor prothrombin complex concentrate (4F-PCC) displayed comparable TGA 's ETP and peak at T1, T2, and T3, whereas direct anti-Xa BR+ patients reversed by 4F-PCC or activated prothrombin complex concentrate (aPCC) reached thrombin generation parameters that exceeded normal range at T2 and T3. CONCLUSIONS: In VKA-treated patients reversed by 4F-PCC, TGA parameters were normalized, whereas in rivaroxaban or apixaban-treated patients reversed by 4F-PCC or aPCC, TGA parameters exceeded normal range. Further studies are needed to compare the efficacy and safety of a different dose of reversal therapy and the impact on coagulation parameters.

Ionized Magnesium: Interpretation and Interest in Atrial Fibrillation.

BACKGROUND: Magnesium (Mg) is often used to manage de novo atrial fibrillation (AF) in the emergency department (ED) and intensive care unit (ICU). Point of care measurement of ionized magnesium (iMg) allows a rapid identification of patients with impaired magnesium status, however, unlike ionized calcium, the interpretation of iMg is not entirely understood. Thus, we evaluated iMg reference values, correlation between iMg and plasmatic magnesium (pMg), and the impact of pH and albumin variations on iMg levels. Secondary objectives were to assess the incidence of hypomagnesemia in de novo AF. METHODS: A total of 236 emergency department and intensive care unit patients with de novo AF, and 198 control patients were included. Reference values were determined in the control population. Correlation and concordance between iMg and pMg were studied using calcium (ionized and plasmatic) as a control in the whole study population. The impact of albumin and pH was assessed in the discordant iMg and pMg values. Lastly, we assessed the incidence of ionized hypomagnesemia (hypoMg) among de novo AF. RESULTS: The reference range values established in our study for iMg were: 0.48-0.65 mmol/L (the manufacturers were: 0.45-0.60 mmol/L). A strong correlation was observed between pMg and iMg (r = 0.85), but, unlike for calcium values, there was no significant impact of pH and albumin in iMg/pMg interpretation. The incidence of hypoMg among de novo AF patients was 8.5% (12.7% using our ranges). When using our ranges, we found a significant link (p = 0.01) between hyopMg and hypokalemia. CONCLUSION: We highlight the need for more accurate reference range values of iMg. Furthermore, our results suggest that blood Mg content is not identical to that of calcium. The incidence of ionized hypomagnesemia among de novo AF patients in our study is 8.5%.

Inhibition of thrombin-activatable fibrinolysis inhibitor via DS-1040 to accelerate clot lysis in patients with acute pulmonary embolism: a randomized phase 1b study.

BACKGROUND: The optimal treatment of intermediate-risk pulmonary embolism (PE) in hemodynamically stable patients remains unknown. Fibrinolytics reduce the risk of hemodynamic deterioration but increase bleeding risk. DS-1040, an inhibitor of thrombin-activatable fibrinolysis inhibitor, enhanced endogenous fibrinolytic activity without increasing bleeding risk in preclinical studies. OBJECTIVES: To evaluate the tolerability and explore the efficacy of DS-1040 in patients with acute PE. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study, ascending doses of intravenous DS-1040 (20-80 mg) or placebo were added to enoxaparin (1 mg/kg twice daily) in patients with intermediate-risk PE. The primary endpoint was the number of patients with major or clinically relevant nonmajor bleeding. The percentage change in thrombus volume and right-to-left ventricular dimensions, assessed using quantitative computed tomography pulmonary angiography, at baseline and after 12 to 72 hours were used to explore the efficacy of DS-1040. RESULTS: Of 125 patients with all available data, 38 were randomized to placebo and 87 to DS-1040. The primary endpoint occurred in 1 patient in the placebo group (2.6%) and 4 patients who received DS-1040 (4.6%). One subject experienced major bleeding (DS-1040 80 mg group); no fatal or intracranial bleeding occurred. Thrombus volume was 25% to 45% lower after infusion, with no differences between the DS-1040 and placebo groups. There was no difference in the change from baseline right-to-left ventricular dimensions between the DS-1040 and placebo groups. CONCLUSION: In patients with acute PE, adding DS-1040 to standard anticoagulation was not associated with an increase in bleeding but did not improve thrombus resolution or right ventricular dilation.

Could reasons for admission help to screen unhealthy alcohol use in emergency departments? A multicenter French study.

Background: Many patients admitted to general emergency departments (EDs) have a pattern of drinking that could lead to future alcohol-related complications. However, it is often difficult to screen these patients in the context of emergency. The aim of this study is to analyze whether reasons for admission could help to screen patients who have an unhealthy alcohol use. Method: Patients were recruited among six public hospital ED in France, between 2012 and 2014. During a one-month period in each hospital, anonymous questionnaires including sociodemographic questions, AUDIT-C and RAPS4-QF were administered to each patients visiting the ED. The reason for admission of each patient was noted at the end of their questionnaire by the ED practitioner. Results: Ten thousand Four hundred twenty-one patients were included in the analysis. Patients who came to the ED for injuries and mental disorders were more likely to report unhealthy alcohol use than non-harmful use or no use. Among male patients under 65 years old admitted to the ED for a mental disorder, 24.2% drank more than four drinks (40 g ethanol) in typical day at least four time a week in the last 12 months. Among these patients, 79.7% reported daily or almost daily heavy episodic drinking (HED, 60 g ethanol), and all were positive on the RAPS4-QF. Conclusion: This study highlights that unhealthy alcohol use is frequent among ED patients and particularly among those who come for injuries or mental disorders. Men under 65 years old with a mental disorder require special attention because of their increased prevalence of daily or almost daily HED.

Major gastrointestinal bleeding in patients receiving anticoagulant therapy for venous thromboembolism.

INTRODUCTION: The gastrointestinal (GI) tract is a frequent site of bleeding in patients receiving anticoagulant therapy for venous thromboembolism (VTE). At-risk patients have not been consistently identified yet. METHODS: We used the RIETE registry to assess the clinical characteristics of patients developing major GI bleeding during the course of anticoagulation. Then, we built a predictive score based on multivariable analysis, aiming to identify patients at increased risk for major GI bleeding. RESULTS: We included 87,431 patients with acute VTE. During the course of anticoagulation, 778 (0.89%) suffered major GI bleeding, 815 (0.93%) non-major GI bleeding and 1462 (1.67%) had major bleeding outside the GI tract. During the first 30 days after major GI bleeding, 7.6% of patients re-bled, 3.9% had VTE recurrences and 33% died. On multivariable analysis, male sex, age ≥70 years, initial VTE presentation as pulmonary embolism, active cancer, prior VTE, recent major bleeding in the GI tract, esophageal varicosities, anemia, abnormal prothrombin time, renal insufficiency and use of corticosteroids were associated to an increased risk for major GI bleeding. Using the predictive score, 39,591 patients (45%) were at low risk; 36,602 (42%) at intermediate-risk; 9315 (11%) at high-risk; and 1923 (2.2%) at very high risk. Their rates of major GI bleeding were: 0.21%, 0.96%, 2.41% and 6.08%, respectively. The c-statistics was 0.771 (95%CI. 0.755-0.786). CONCLUSIONS: We have developed a score which has the potential to identify patients at increased risk for GI bleeding, but needs to be externally validated."