Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients.

BACKGROUND: Antifibrinolytics reduce death from bleeding in trauma and post-partum haemorrhage. We examined the effect of treatment delay on the effectiveness of antifibrinolytics. METHODS: We did an individual patient-level data meta-analysis of randomised trials done with more than 1000 patients that assessed antifibrinolytics in acute severe bleeding. We identified trials done between Jan 1, 1946, and April 7, 2017, from MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, PubMed, Popline, and the WHO International Clinical Trials Registry Platform. The primary measure of treatment benefit was absence of death from bleeding. We examined the effect of treatment delay on treatment effectiveness using logistic regression models. We investigated the effect of measurement error (misclassification) in sensitivity analyses. This study is registered with PROSPERO, number 42016052155. FINDINGS: We obtained data for 40 138 patients from two randomised trials of tranexamic acid in acute severe bleeding (traumatic and post-partum haemorrhage). Overall, there were 3558 deaths, of which 1408 (40%) were from bleeding. Most (884 [63%] of 1408) bleeding deaths occurred within 12 h of onset. Deaths from post-partum haemorrhage peaked 2-3 h after childbirth. Tranexamic acid significantly increased overall survival from bleeding (odds ratio [OR] 1·20, 95% CI 1·08-1·33; p=0·001), with no heterogeneity by site of bleeding (interaction p=0·7243). Treatment delay reduced the treatment benefit (p<0·0001). Immediate treatment improved survival by more than 70% (OR 1·72, 95% CI 1·42-2·10; p<0·0001). Thereafter, the survival benefit decreased by 10% for every 15 min of treatment delay until 3 h, after which there was no benefit. There was no increase in vascular occlusive events with tranexamic acid, with no heterogeneity by site of bleeding (p=0·5956). Treatment delay did not modify the effect of tranexamic acid on vascular occlusive events. INTERPRETATION: Death from bleeding occurs soon after onset and even a short delay in treatment reduces the benefit of tranexamic acid administration. Patients must be treated immediately. Further research is needed to deepen our understanding of the mechanism of action of tranexamic acid. FUNDING: UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation (CRASH-2 trial). London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation (WOMAN trial)

A regional trauma system to optimize the pre-hospital triage of trauma patients.

INTRODUCTION: Pre-hospital triage is a key element in a trauma system that aims to admit patients to the most suitable trauma center, and may decrease intra-hospital mortality. We evaluated the performance of a pre-hospital procedure in a regional trauma system through measurements of the quality of pre-hospital medical assessment and the efficacy of a triage protocol. METHODS: Our regional trauma system included 13 hospitals categorized as Level I, II or III trauma centers according to their technical facilities. Each patient was graded A, B or C by an emergency physician, according to the seriousness of their injuries at presentation on scene. The triage was performed according to this grading and the categorization of centers. This study is a registry analysis of a three-year period (2009 to 2011). RESULTS: Of the 3,428 studied patients, 2,572 were graded using the pre-hospital grading system (Graded group). The pre-hospital gradation was closely related with injury severity score (ISS) and intra-hospital mortality rate. The triage protocol had a sensitivity of 92% (95% confidence interval (CI) 90% to 93%) and a specificity of 41% (95% CI 39% to 44%) to predict adequate admission of patients with ISS more than 15. A total of 856 patients were not graded at the scene (Non-graded group). Undertriage rate was significantly reduced in the Graded group compared with the Non-graded group, with a relative risk of 0.47 (95% CI 0.40 to 0.56) according to the definition of the American College of Surgeons Committee on Trauma (P <0.001). Where adjusted for trauma severity, the expected mortality rate at discharge from hospital was higher than observed mortality, with a difference of +2.0% (95% CI 1.4 to 2.6%; P <0.01). CONCLUSIONS: Implementation of a regional trauma system with a pre-hospital triage procedure was effective in detecting severe trauma patients and in lowering the rate of pre-hospital undertriage. A beneficial effect on outcome of such an organization is suggested

Management of upper gastrointestinal bleeding in emergency departments, from bleeding symptoms to diagnosis: a prospective, multicenter, observational study.

BACKGROUND: Upper gastrointestinal bleeding (UGB) is common in emergency departments (EDs) and can be caused by many eso-gastro-duodenal lesions. Most available epidemiological data and data on the management of UGB comes from specialized departments (intensive care units or gastroenterology departments), but little is known from the ED perspective. We aimed to determine the distribution of symptoms revealing UGB in EDs and the hemorrhagic lesions identified by endoscopy. We also describe the characteristics of patients consulting for UGB, UGB management in the ED and patients outcomes. METHOD: This was a prospective, observational, multicenter study covering 4 consecutive days in November 2013. Participating EDs were part of the Initiatives de Recherche aux Urgences network coordinated by the French Society of Emergency Medicine. All patients with suspected UGB in these EDs were included. RESULTS: In total, 110 EDs participated, including 194 patients with suspected UGB (median age 66 years [Q1-Q3: 51-81]). Overall, 104 patients (54%) had hematemesis and 75 (39%) melena. Endoscopy revealed lesions in 121 patients, mainly gastroduodenal ulcer or ulcerations (41%) or bleeding lesions due to portal hypertension (20%). The final diagnosis of UGB was reversed by endoscopy in only 3% of cases. Overall, 67 patients (35%) had at least one severity sign. Twenty-one patients died (11%); 40 (21%) were hospitalized in intensive care units and 126 (65%) in medicine departments; 28 (14%) were outpatients. Mortality was higher among patients with clinical and biological severity signs. CONCLUSION: Most of the UGB cases in EDs are revealed by hematemesis. The emergency physician diagnosis of UGB is rarely challenged by the endoscopic findings

Intranasal sufentanil versus intravenous morphine for acute severe trauma pain: A double-blind randomized non-inferiority study.

BACKGROUND: Intravenous morphine (IVM) is the most common strong analgesic used in trauma, but is associated with a clear time limitation related to the need to obtain an access route. The intranasal (IN) route provides easy administration with a fast peak action time due to high vascularization and the absence of first-pass metabolism. We aimed to determine whether IN sufentanil (INS) for patients presenting to an emergency department with acute severe traumatic pain results in a reduction in pain intensity non-inferior to IVM. METHODS AND FINDINGS: In a prospective, randomized, multicenter non-inferiority trial conducted in the emergency departments of 6 hospitals across France, patients were randomized 1:1 to INS titration (0.3 μg/kg and additional doses of 0.15 μg/kg at 10 minutes and 20 minutes if numerical pain rating scale [NRS] > 3) and intravenous placebo, or to IVM (0.1 mg/kg and additional doses of 0.05 mg/kg at 10 minutes and 20 minutes if NRS > 3) and IN placebo. Patients, clinical staff, and research staff were blinded to the treatment allocation. The primary endpoint was the total decrease on NRS at 30 minutes after first administration. The prespecified non-inferiority margin was -1.3 on the NRS. The primary outcome was analyzed per protocol. Adverse events were prospectively recorded during 4 hours. Among the 194 patients enrolled in the emergency department cohort between November 4, 2013, and April 10, 2016, 157 were randomized, and the protocol was correctly administered in 136 (69 IVM group, 67 INS group, per protocol population, 76% men, median age 40 [IQR 29 to 54] years). The mean difference between NRS at first administration and NRS at 30 minutes was -4.1 (97.5% CI -4.6 to -3.6) in the IVM group and -5.2 (97.5% CI -5.7 to -4.6) in the INS group. Non-inferiority was demonstrated (p < 0.001 with 1-sided mean-equivalence t test), as the lower 97.5% confidence interval of 0.29 (97.5% CI 0.29 to 1.93) was above the prespecified margin of -1.3. INS was superior to IVM (intention to treat analysis: p = 0.034), but without a clinically significant difference in mean NRS between groups. Six severe adverse events were observed in the INS group and 2 in the IVM group (number needed to harm: 17), including an apparent imbalance for hypoxemia (3 in the INS group versus 1 in the IVM group) and for bradypnea (2 in the INS group versus 0 in the IVM group). The main limitation of the study was that the choice of concomitant analgesics, when they were used, was left to the discretion of the physician in charge, and co-analgesia was more often used in the IVM group. Moreover, the size of the study did not allow us to conclude with certainty about the safety of INS in emergency settings. CONCLUSIONS: We confirm the non-inferiority of INS compared to IVM for pain reduction at 30 minutes after administration in patients with severe traumatic pain presenting to an emergency department. The IN route, with no need to obtain a venous route, may allow early and effective analgesia in emergency settings and in difficult situations. Confirmation of the safety profile of INS will require further larger studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02095366. EudraCT 2013-001665-16

The genus Serratia revisited by genomics

The genus Serratia has been studied for over a century and includes clinically-important and diverse environmental members. Despite this, there is a paucity of genomic information across the genus and a robust whole genome-based phylogenetic framework is lacking. Here, we have assembled and analysed a representative set of 664 genomes from across the genus, including 215 historic isolates originally used in defining the genus. Phylogenomic analysis of the genus reveals a clearly-defined population structure which displays deep divisions and aligns with ecological niche, as well as striking congruence between historical biochemical phenotyping data and contemporary genomics data. We highlight the genomic, phenotypic and plasmid diversity of Serratia, and provide evidence of different patterns of gene flow across the genus. Our work provides a framework for understanding the emergence of clinical and other lineages of Serratia

Peasant settlers and the ‘civilizing mission’ in Russian Turkestan, 1865-1917

This article provides an introduction to one of the lesser-known examples of European settler colonialism, the settlement of European (mainly Russian and Ukrainian) peasants in Southern Central Asia (Turkestan) in the late nineteenth and early twentieth centuries. It establishes the legal background and demographic impact of peasant settlement, and the role played by the state in organising and encouraging it. It explores official attitudes towards the settlers (which were often very negative), and their relations with the local Kazakh and Kyrgyz population. The article adopts a comparative framework, looking at Turkestan alongside Algeria and Southern Africa, and seeking to establish whether paradigms developed in the study of other settler societies (such as the ‘poor white’) are of any relevance in understanding Slavic peasant settlement in Turkestan. It concludes that there are many close parallels with European settlement in other regions with large indigenous populations, but that racial ideology played a much less important role in the Russian case compared to religious divisions and fears of cultural backsliding. This did not prevent relations between settlers and the ‘native’ population deteriorating markedly in the years before the First World War, resulting in large-scale rebellion in 1916

Évaluation de critères de triage pour les traumatismes graves (données du "trauma system" du réseau nord alpin des urgences (TRENAU))

Introduction : Les trauma system américains ont montré leur efficacité par la diminution de la mortalité, en structurant des filières de soins avec une démarche d assurance qualité. Afin d améliorer la qualité des soins, le Réseau Nord Alpin des urgences a mis en place une organisation des soins de type trauma system intégrant le haut niveau d expertise des SAMU. L objectif de cette étude est d évaluer la pertinence des critères de triage du Trauma system du Réseau Nord Alpin des Urgences (TRENAU) comme critères prédictifs de gravité. Méthode : Les centres hospitaliers de la région sont catégorisés (par niveaux de I à III) en fonction des ressources disponibles dans l établissement. Les patients sont inclus dans le registre selon les critères définis par la conférence de Vittel et classés en trois groupes en fonction de leur sévérité. La procédure de triage initiale intègre le niveau des centres, la gravité du patient et la nécessité d un plateau technique spécialisé. Nous avons réalisé une étude rétrospective à partir de données du registre du TRENAU afin d évaluer les critères de triage choisis. Les patients inclus sont les patients traumatisés grave présentant un ou plusieurs critères de Vittel et enregistrés dans le registre du TRENAU. Une méthode de régression linéaire multiple a été employée pour rechercher les facteurs en corrélation avec l Injury Severity Score (ISS). Résultats : 179 patients ont été inclus, dont 77% de sexe masculin et un âge médian de 29 ans. L étude montre que les Grade A et B sont fortement corrélés à l ISS. Les Grades C correspondent à un sur triage (overtriage), se justifiant par le recours à une intervention urgente (chirurgie ou radiologie interventionnelle) dans 10 % des cas, et l admission en réanimation de plus d un tiers des patients. Conclusion : Les critères de Grade A et B retenus par le TRENAU pour définir les grades de gravité montrent une association avec la sévérité du traumatisme. Le Grade C doit être amélioré.Background: The American trauma system showed its efficiency by the decrease of the mortality. The trauma system of the northen french Alps emergency network was created in this model to improve the quality of care in ours region. The goal of this work is to estimate the relevance of the triage criteria chosen by the TRENAU as predictive criteria of severity. Methods: The hospitals of the region were categorized (by level I to III) according to the available resources in the etabishment.The patients were included in the register according to the criteria defined by the conference of Vittel and classified in three groups accordind to their severity.The inital prodecure of triage integrates the level of the centers, the trauma severity and the necessity of specialized cares . We realized a prospective study from data of the register of the TRENAU to estimate the chosen triage criteria.The inclusive patients are severe injured patients, presenting one or several criteria of Vittel and were recorded in the register of the TRENAU. A methode of multiple linear regression was employed to look for factors in correlation with an Injury severity score (ISS). Results: The analysis concerned 179 patients, among which 77% male with a median age of 29 years.The study shows that the Rank A and B are strongly correlated with an ISS>15.The Ranks C correspond to one overtriage , justifying itself by the appeal to an urgent intervention (surgery or interventional radiology) in 10% of the case, and the admittance of rescucitation of more than a third of the patients. Conclusion: The Rank A and B retained by the the TRENAU to define the rank of gravity show an association with the severity of the trauma. The Rank C must be improved.GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Survival is surfing on the guidelines wave

International audienc

Le médecin généraliste dans le cinéma français de fiction des années cinquante à nos jours

NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocPARIS-Académie Médecine (751065201) / SudocSudocFranceF

Le médecin dans les séries télévisées françaises des années 70 à nos jours

Cette étude observationnelle descriptive, à travers une analyse qualitative et quantitative de 28 personnages de médecin dans 15 séries télévisées, décrit l'évolution de la représentation du médecin dans les séries télévisées françaises et en apprécie son réalisme. Le médecin des séries télévisées françaises est un homme blanc de 36 ans, hétérosexuel, célibataire et sans enfant, au physique avantageux. Sympathique et décontracté, il est en bonne santé. L'exercice de la médecine générale libérale, très majoritaire dans les années 70 et 80, a laissé place à un exercice spécialisé et salarié ces 20 dernières années. Le médecin des séries télévisées travaille essentiellement en association avec des confrères dans les zones urbaines. Ses compétences sont reconnues avec une satisfaction importante des patients. Son image est très majoritairement positive. Les séries télévisées s'éloignent bien souvent de la réalité de la démographie médicale française. Alors que la représentation du médecin dans les séries télévisées françaises est proche de sa représentation cinématographique, un personnage sérieux et fondamentalement humain, nous constatons un décalage important par rapport à sa représentation outre-atlantique où il apparaît de plus en plus comme un expert plaçant le diagnostic au centre de ses préoccupations. L'évolution du personnage du médecin dans les séries télévisées est un reflet populaire de l'évolution de la société. Inversement, il faut souligner l' influence profonde de la télévision, et en particulier des séries télévisées, sur la perception des vrais médecins par le public.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF