Publications by authors named "Laurent Jacquin"

23 Publications

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Cancer Patients' Prehospital Emergency Care: Post Hoc Analysis from the French Prospective Multicenter Study EPICANCER.

J Clin Med 2021 Mar 9;10(5). Epub 2021 Mar 9.

Centre of Research in Epidemiology and StatisticS (CRESS), INSERM, UMR 1153, Epidemiology and Clinical Statistics for Tumor, Respiratory, and Resuscitation Assessments (ECSTRRA) Team, University of Paris, 75006 Paris, France.

Background: Very little data are available concerning the prehospital emergency care of cancer patients. The objective of this study is to report the trajectories and outcomes of cancer patients attended by prehospital emergency services.

Methods: This was an ancillary study from a three-day cross-sectional prospective multicenter study in France. Adult patients with cancer were included if they called the emergency medical dispatch center Service d'Aide Médicale Urgente (SAMU). The study was registered on ClinicalTrials.gov (NCT03393260, accessed on 8th January 2018).

Results: During the study period, 1081 cancer patients called the SAMU. The three most frequent reasons were dyspnea (20.2%), neurological disorder (15.4%), and fatigue (13.1%). Among those patients, 949 (87.8%) were directed to the hospital, among which 802 (90.8%) were directed to an emergency department (ED) and 44 (5%) were transported directly to an intensive care unit (ICU). A mobile intensive care unit (MICU) was dispatched 213 (31.6%) times. The decision to dispatch an MICU seemed generally based on the patient's reason for seeking emergency care and the presence of severity signs rather than on the malignancy or the patient general health status. Among the patients who were directed to the ED, 98 (16.1%) were deceased on day 30. Mortality was 15.4% for those patients directed to the ED but who were not admitted to the ICU in the next 7 days, 28.2% for those who were admitted to ICU in the next 7 days, and 56.1% for those patients transported by the MICU directly to the ICU.

Conclusion: Cancer patients attending prehospital emergency care were most often directed to EDs. Patients who were directly transported to the ICU had a high mortality rate, raising the question of improving triage policies.
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http://dx.doi.org/10.3390/jcm10051145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967166PMC
March 2021

Strategies used by emergency care professionals to handle interpersonal difficulties with patients: a qualitative study.

BMJ Open 2021 02 8;11(2):e042362. Epub 2021 Feb 8.

Public Health Department, Hospices Civils de Lyon, F-69003 Lyon, France

Objectives: Identify the strategies implemented by emergency care professionals when facing tension and interpersonal violence from patients and their friends and family.

Design: Descriptive qualitative study based on 38 semidirective interviews.

Participants: Doctors, nurses, nursing assistants and administrative staff.

Setting: Four emergency departments (EDs) from three French university hospitals.

Results: According to the medical professionals interviewed, the difficulties that they encounter with patients or their accompanying family members can be explained by a lack of understanding of the functioning of EDs, by a general increase in individualistic behaviours leading to a lack of civility or by deviant behaviours (related to toxic substance abuse or mental illness). While managing deviant behaviours may sometimes require a collective intervention, ED staff also implement what are essentially individual communication strategies (with the use of rational explanation, seduction and empathy), confrontation or flight to deal with interpersonal difficulties.

Conclusions: Strategies used by staff members tend to be individualised for the most part, and some, such as confrontational or escape strategies, may not be adapted to all situations. In the face of difficulties between staff and patients, mediators, specialised in resolving conflict, could entrust some cases to professionals.

Trial Registration Number: ClinicalTrials.gov Registry (NCT03139110).
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http://dx.doi.org/10.1136/bmjopen-2020-042362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871700PMC
February 2021

Difficulty of the ethical decision-making process in withholding and withdrawing life-sustaining treatments in French EDs during COVID pandemic.

Scand J Trauma Resusc Emerg Med 2020 Aug 13;28(1):78. Epub 2020 Aug 13.

UMR ADéS 7268, Aix-Marseille University/ EFS / CNRS, Espace éthique méditerranéen, Timone Adulte's Hospital, Marseille, France.

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http://dx.doi.org/10.1186/s13049-020-00772-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424240PMC
August 2020

[Mediators in emergency services: what missions according to the staff?]

Sante Publique 2019 November December;31(6):797-807

Objectives: Violence in emergency services has become a central issue in the daily work of hospital employees. While the use of video surveillance and the training of professionals in conflict management are the most common methods used, there are few cases using the setting up of a third part such as a mediator. We conducted a qualitative study with professionals to examine their representations associated with mediation.

Method: Semi-directive interviews were conducted with professionals from four emergency units. The topics discussed in interviews were the definition of mediation and the missions that the mediators should fulfil. The content of 38 semi-directive interviews was analysed according to the inductive approach of the grounded theory. A content analysis was made, followed by an analysis aiming to bring out types and convergences/divergences.

Results: Professionals were not aware of the definition of mediation and of its missions. They linked to it an instrumental theme, making mediation a tool for conflict prevention and management, a tool for communication with patients about their care, and about the organisation of emergency unit. The upcoming presence of mediators was seen as an help. A potential competition between professionals and mediators in the tasks performed was identified.

Conclusion: The study shows a favourable opinion towards mediation. It has allowed to identify obstacles to the well-functioning of the missions assigned to mediators. One of the challenges is the integration of this new actor, the mediator.
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http://dx.doi.org/10.3917/spub.196.0797DOI Listing
June 2020

Management of decision of withholding and withdrawing life-sustaining treatments in French EDs.

Scand J Trauma Resusc Emerg Med 2020 Jun 8;28(1):52. Epub 2020 Jun 8.

RESCUe-RESUVal Network, Lucien Hussel Hospital, Montée du Dr Chapuis, 38209, Vienne, BP 127, France.

Background: Decisions of withholding or withdrawing life sustaining-treatments in emergency department are part of current practice but the decision-making process remains poorly described in the literature.

Study Objective: We conducted a study in two phases, the first comprising a retrospective chart review study of patients dying in the ED and the second comprising survey study of health care workers at 10 urban emergency departments in France.

Method: In a first step, we analyzed medical records based on fifteen criteria of the decision-making process grouped into four categories: the collegiality, the traceability, the management and the communication as recommended by the international guidelines. In a second step, we conducted an auto-administrated survey to assess how the staff members (medical, paramedical) feel with the decision-making process.

Results: There were 273 deaths which occurred in the ED over the study period and we included 145 (53.1%) patients. The first-step analysis revealed that the traceability of the decision and the information given to patient or the relatives were the most reported points according to the recommendations. Three of the ten emergency departments had developed a written procedure. The collegial discussion and the traceability of the prognosis assessment were significantly increased in emergency department with a written procedure as well as management of pain, comfort care, and the communication with the patient or the relatives. In the second-step analysis, among the 735 staff members asked to take part in the survey, 287 (39.0%) answered. The medical and paramedical staff expressed difficult experience regarding the announcement and the communication with the patient and the relatives.

Conclusion: The management of the decision to withhold or withdraw life-sustaining treatments must be improved in emergency departments according to the guidelines. A standard written procedure could be useful in clinical practice despite the lack of experienced difference between centers with and without procedures.
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http://dx.doi.org/10.1186/s13049-020-00744-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282105PMC
June 2020

Inhaled methoxyflurane for the management of trauma related pain in patients admitted to hospital emergency departments: a randomised, double-blind placebo-controlled trial (PenASAP study).

Eur J Emerg Med 2020 Dec;27(6):414-421

Emergency Department SAMU 93 Inserm U942, AP-HP Hôpital Avicenne l, Bobigny, France.

Background: Oligo-analgesia is common in the emergency department (ED). This study aimed at reporting, when initiated by triage nurse, the superior efficacy of inhaled methoxyflurane plus standard of care (m-SoC) analgesia versus placebo plus SoC (p-SoC) for moderate-to-severe trauma-related pain in the hospital ED.

Methods: A randomised, double-blind, placebo-controlled trial was conducted at eight EDs. Adults with pain score ≥4 (11-point numerical rate scale, NRS) at admission were randomised to receive one or two inhalers containing m-SoC or p-SoC. Primary outcome measure was time until pain relief ≤30 mm, assessed on the 100-mm Visual Analogic Scale (VAS).

Results: A total of 351 patients were analysed (178 m-SoC; 173 p-SoC). Median pain prior to first inhalation was 66 mm, 75% had severe pain (NRS 6-10). Median time to pain relief was 35 min [95% confidence interval (CI), 28-62] for m-SoC versus not reached in p-SoC (92 - not reached) [hazard ratio), 1.93 (1.43-2.60), P < 0.001]. Pain relief was most pronounced in the severe pain subgroup: hazard ratio, 2.5 (1.7-3.7). As SoC, 24 (7%) patients received weak opioids (6 versus 8%), 4 (1%) strong opioid and 44 (13%) escalated to weak or strong opioids (8 versus 17%, respectively, P = 0.02). Most adverse events were of mild (111/147) intensity.

Conclusions: In this study, we report that methoxyflurane, initiated at triage nurse as part of a multimodal analgesic approach, is effective in achieving pain relief for trauma patients. This effect was particularly pronounced in the severe pain subgroup.
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http://dx.doi.org/10.1097/MEJ.0000000000000686DOI Listing
December 2020

Symptoms of anxiety and depression in relatives after decisions of withholding and withdrawing life-sustaining treatments in emergency departments.

Eur J Emerg Med 2020 Oct;27(5):338-343

Service d'Accueil des Urgences, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon.

Objective: The aim of our study was to assess anxiety and depression in patients' relatives after a decision of withholding and withdrawing life-sustaining treatments.

Methods: We conducted a prospective observational multicenter study in three university hospitals' emergency departments. The Hospital Anxiety and Depression Scale (HADS) was assessed on the relatives of patients admitted in emergency departments 3 days and 21 days after the decision of withholding or withdrawing life-sustaining treatments.

Results: Among the 109 patients with a decision of withholding or withdrawing life-sustaining treatments, 88 relatives were included and 74 (67, 8%) completed the 21-day follow up. Among those, 14 (18.9%) and 13 (17.6%) displayed symptoms of anxiety and depression at 3 days, respectively. After 21 days, symptoms anxiety and depression were still present in the same way for nine (12.2%) of the relatives. The median total HADS score was 13.5 [interquartile range (IQR): 8-16] at 3 days and 10 [IQR: 5-17] at 21 days. The symptoms of depression at 21 days were more frequent for the relatives of patients who died at 21 days (P = 0.03).

Conclusion: We found symptoms of anxiety and depression in relatives after decisions of withholding and withdrawing life-sustaining treatments in emergency departments, which persist at 21 days. Further studies are needed to support these results and to search the relatives at risk to develop these symptoms.
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http://dx.doi.org/10.1097/MEJ.0000000000000669DOI Listing
October 2020

Poor Involvement of General Practitioners in Decisions of Withholding or Withdrawing Life-Sustaining Treatment in Emergency Departments.

J Gen Intern Med 2020 01 4;35(1):177-181. Epub 2019 Nov 4.

Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Accueil des urgences, 5 place d'Arsonval, F-69003, Lyon, France.

Background: Decisions of withholding or withdrawing life-sustaining treatment are frequent in emergency departments (ED) and patients are often unable to communicate their wishes concerning end of life desires.

Objective: To evaluate the participation of general practitioners (GPs) during the decision-making process of withholding or withdrawing life-sustaining treatments in ED.

Design: Prospective observational multicenter study.

Patients: We included patients for whom a decision of withdrawing or withholding life-sustaining treatments was made in ED. For each patient, we enrolled one general practitioner.

Main Measures: GPs were interviewed about their perception of end of life patient's management and the communication with ED and families.

Key Results: There were 109 potential patient participants. We obtained answers from 54 (49.5%) of the patient's associated GPs. Only 4 (7.4%) GPs were involved during the decision-making process of withholding or withdrawing life-sustaining treatments. Among GPs, 29 (53.7%) were contacted by family after the decision, most often to talk about their difficult experience with the decision. A majority (94%) believed their involvements in these decisions were important and 68% wished to "always" participate in end of life decisions despite the fact that they usually don't participate in these decisions. Finally, 66% of GPs believed that management of end of life in the emergency department was a failure and should be anticipated.

Conclusions: GPs would like to be more involved and barriers to GP involvement need to be overcome. We do not have any outcome data to suggest that routine involvement of GPs in all end of life patients improves their outcomes. Moreover, it requires major system and process-based changes to involve all primary care physicians in ED decision-making.

Nih Trial Registry Number: NCT02844972.
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http://dx.doi.org/10.1007/s11606-019-05464-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957665PMC
January 2020

Difficulty of the decision-making process in emergency departments for end-of-life patients.

J Eval Clin Pract 2019 Dec 9;25(6):1193-1199. Epub 2019 Jul 9.

Hospices Civiles de Lyon, Hôpital Edouard Herriot, Service d'Accueil des urgences, 5 place d'Arsonval, Lyon, F-69003, France.

Background: In emergency departments, for some patients, death is preceded by a decision of withholding or withdrawing life-sustaining treatments. This concerns mainly patients over 80, with many comorbidities. The decision-making process of these decisions in emergency departments has not been extensively studied, especially for noncommunicating patients.

Aim: The purpose of this study is to describe the decision-making process of withholding and withdrawing life-sustaining treatments in emergency departments for noncommunicating patients and the outcome of said patients.

Design: We conducted a prospective multicenter study in three emergency departments of university hospitals from September 2015 to January 2017.

Results: We included 109 patients in the study. Fifty-eight (53.2%) patients were coming from nursing homes and 52 (47.7%) patients had dementia. Decisions of withholding life-sustaining treatment concerned 93 patients (85.3%) and were more frequent when a surrogate decision maker was present 61 (65.6%) versus seven (43.8%) patients. The most relevant factors that lead to these decisions were previous functional limitation (71.6%) and age (69.7%). Decision was taken by two physicians for 80 patients (73.4%). The nursing staff and general practitioner were, respectively, involved in 31 (28.4%) and two (1.8%) patients. A majority of the patients had no advance directives (89.9%), and the relatives were implicated in the decision-making process for 96 patients (88.1%). Death in emergency departments occurred for 47 patients (43.1%), and after 21 days, 84 patients (77.1 %) died.

Conclusion: There is little anticipation in end-of-life decisions. Discussion with patients concerning their end-of-life wishes and the writing of advance directives, especially for patients with chronic diseases, must be encouraged early.
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http://dx.doi.org/10.1111/jep.13229DOI Listing
December 2019

Intensity of care delivered by prehospital emergency medical service physicians to patients with deliberate self-poisoning: results from a 2-day cross-sectional study in France.

Intern Emerg Med 2019 09 18;14(6):981-988. Epub 2019 May 18.

Department of Emergency Medicine, Ambroise Paré Hospital, APHP, University Paris Diderot, INSERM UMR-S 1144, Paris, France.

Emergency management of deliberate self-poisoning (DSP) by drug overdose is common in emergency medicine. There is a paucity of data about the prehospital care of these patients. The principal aim was to describe the intensity of care received by patients with DSP who were managed by prehospital emergency medical service (EMS) physicians. A 48-h cross-sectional study was conducted in 319 EMS and emergency units in France. Patient and poisoning characteristics and treatments administered were recorded. Complications of poisoning, hospitalization, intensive care unit admission and death were recorded until day 30. The primary endpoint was the probability of receiving prehospital intensive care, including fluid resuscitation, vasopressor therapy, invasive ventilation, or antidotal treatments, depending whether prehospital treatment was carried out by an EMS physician or not. Data from 703 patients (median age was 43 [30-52] years, 288 (40%) men) were analyzed. One hundred and fifteen (16%) patients were attended by an EMS physician. Patients attended by EMS physicians were more likely to receive intensive treatment in the prehospital setting [odds ratio (OR) 7.4, 95% confidence interval 4.3-12.9]. These patients had more severe poisoning as suggested mainly by a lower Glasgow Coma Score (13 [8-15] vs. 15 [15-15]; p < 0.001) and a higher rate of admission to an intensive care unit [29 (25%) vs. 15 (2%), p < 0.001]. Patients with DSP attended by prehospital EMS physicians frequently received intensive care. The level of care seemed appropriate for the severity of the poisoning.
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http://dx.doi.org/10.1007/s11739-019-02108-1DOI Listing
September 2019

Answer to the reply letter to: Physician's experience in decisions of withholding, withdrawing life-sustaining treatments: A multicentre survey in emergency departments.

Anaesth Crit Care Pain Med 2019 10 23;38(5):519-520. Epub 2019 Feb 23.

UMR 7268 ADéS, Aix-Marseille Université/EFS/CNRS, Faculté de Médecine, 27, boulevard Jean-Moulin, Marseille 13005, France. Electronic address:

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http://dx.doi.org/10.1016/j.accpm.2019.02.006DOI Listing
October 2019

Physicians' experience in decisions of withholding and withdrawing life-sustaining treatments: A multicenter survey into emergency departments.

Anaesth Crit Care Pain Med 2018 12 27;37(6):633-634. Epub 2018 Sep 27.

UMR 7268 ADéS Aix-Marseille université, EFS, CNRS, efaculté de médecine de Marseille , hôpital adultes La Timone, 27, boulevard Jean-Moulin 13005 Marseille, France. Electronic address:

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http://dx.doi.org/10.1016/j.accpm.2018.09.007DOI Listing
December 2018

Diagnostic accuracy of loop-mediated isothermal amplification (LAMP) for screening patients with imported malaria in a non-endemic setting.

Parasite 2017 18;24:53. Epub 2017 Dec 18.

Institute of Parasitology and Medical Mycology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, 69004 Lyon, France - Malaria Research Unit, SMITh, ICBMS, UMR 5246 CNRS-INSA-CPE-University Lyon1, 69100 Villeurbanne, France.

Background: Sensitive and easy-to-perform methods for the diagnosis of malaria are not yet available. Improving the limit of detection and following the requirements for certification are issues to be addressed in both endemic and non-endemic settings. The aim of this study was to test whether loop-mediated isothermal amplification of DNA (LAMP) may be an alternative to microscopy or real-time PCR for the screening of imported malaria cases in non-endemic area.

Results: 310 blood samples associated with 829 suspected cases of imported malaria were tested during a one year period. Microscopy (thin and thick stained blood slides, reference standard) was used for the diagnosis. Real-time PCR was used as a standard of truth, and LAMP (Meridian Malaria Plus) was used as an index test in a prospective study conducted following the Standards for Reporting Diagnosis Accuracy Studies. In the 83 positive samples, species identification was P. falciparum (n = 66), P. ovale (n = 9), P. vivax (n = 3) P. malariae (n = 3) and 2 co-infections with P. falciparum + P.malariae. Using LAMP methods, 93 samples gave positive results, including 4 false-positives. Sensitivity, specificity, positive predictive value and negative predictive value for LAMP tests were 100%, 98.13%, 95.51%, and 100% compared to PCR.

Conclusion: High negative predictive value, and limit of detection suggest that LAMP can be used for screening of imported malaria cases in non-endemic countries when expert microscopists are not immediately available. However, the rare occurrence of non-valid results and the need for species identification and quantification of positive samples preclude the use of LAMP as a single reference method.
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http://dx.doi.org/10.1051/parasite/2017054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734902PMC
July 2018

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

Scand J Trauma Resusc Emerg Med 2017 Aug 14;25(1):78. Epub 2017 Aug 14.

Service des Urgences - Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.

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.
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http://dx.doi.org/10.1186/s13049-017-0425-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557479PMC
August 2017

Emergency medicine as a primary specialty-French emergency medicine residents' attitudes.

CJEM 2015 Nov 23;17(6):689-91. Epub 2015 Mar 23.

*Service des Urgences,Saint-Antoine,Assistance Publique des Hôpitaux de Paris,Paris.

Emergency medicine (EM) has been a fellowship program (supra-specialty) in France since 2004. Even though the program can be accessed after completion of one of several primary specialties, the vast majority (97%) of its residents enter the program after having completed training in family medicine. A change to develop a primary EM specialty is being discussed. Our objective was to assess French residents and young EM physicians' attitudes toward EM as a primary specialty. We conducted a brief cross-sectional online survey among young EM physicians and trainees in November and December 2012. There were 288 respondents to the survey. Forty-nine percent (n=142) of respondents would have chosen EM if it was a primary specialty, but 73% (n=209) prefer maintaining the status quo, offering EM training as a supra-specialty fellowship program. Work-related quality of life was the main reason for those not choosing EM as a primary specialty.
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http://dx.doi.org/10.1017/cem.2014.64DOI Listing
November 2015

Optimized acute stroke pathway using medical advanced regulation for stroke and repeated public awareness campaigns.

Am J Emerg Med 2014 Mar 14;32(3):225-32. Epub 2013 Nov 14.

Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Accueil des Urgences Médicales, 69003 Lyon, France. Electronic address:

Objective: The aim of this study is to evaluate the efficiency of a specific organizational model for early stroke management associated with repeated public awareness campaigns on stroke warning signs.

Method: Our model is based on initial telephone triage of potential candidates for an intravenous thrombolysis by an emergency physician before a 3-party conference including basic life support team on scene and a stroke neurologist. We performed a time series analysis for a period of 5 years and a half, comparing the number of emergency telephone calls with that of intravenous thrombolysis treatment realized.

Results: In our organizational model, repeated awareness public campaigns increased both the number of emergency calls for suspected stroke and the selection of potential candidates for intravenous thrombolysis. Results from the time series analysis suggest that educational campaigns are a major factor influencing our emergency medical service activity. This result is correlated with the number of performed intravenous thrombolyses by the stroke center especially within a 3-hour delay (Spearman ρ, P = .621, P = .000 and P = .439, P = .000, respectively).

Conclusion: Educational programs repeated each year are useful to the population for learning how to recognize stroke symptoms and send straight away an emergency call. Combining the emergency action with an early remote evaluation by the stroke center team and a direct admission in imaging department shortens the time-to-treatment delay. This model is reproducible in different health care systems.
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http://dx.doi.org/10.1016/j.ajem.2013.11.018DOI Listing
March 2014

Search for adenosine A2A spare receptors on peripheral human lymphocytes.

FEBS Open Bio 2013 17;3:1-5. Epub 2012 Nov 17.

Aix-Marseille Université, UMR MD2, Faculté de Médecine Nord, Marseille, France.

Some ligand-receptor couples involve spare receptors, which are apparent when a maximal response is achieved with only a small fraction of the receptor population occupied. This situation favours cross-reactions with low-affinity ligands, which may be detrimental for cell signaling. In the case of the adenosine A2A receptors (A2AR), which have an immunosuppressive effect on lymphocytes through cAMP production, the presence of spare A2AR remains to be established. We examined the situation using patients over-expressing lymphocyte A2AR and an agonist-like mAb to A2AR. We found that maximal mAb binding and functional response varied among the patients whereas the dissociation constant and half-maximal effective concentration had similar mean values (0.19 and 0.18 μM, respectively). Lymphocyte A2AR expression was correlated to plasma adenosine level and A2AR occupation but not to A2AR response. These results are consistent with a lack of a reserve of functional A2AR on human lymphocytes as a general rule and suggest that the amount and functional state of the expressed A2AR determine the maximal level of the lymphocyte response to adenosine.
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http://dx.doi.org/10.1016/j.fob.2012.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668538PMC
July 2013

Biological efficacy of a 600 mg loading dose of clopidogrel in ST-elevation myocardial infarction.

Thromb Haemost 2012 Jul 26;108(1):101-6. Epub 2012 Apr 26.

Département de Cardiologie, Hôpital Universitaire Nord, Aix-Marseille University, Marseille, France.

Optimal platelet reactivity (PR) inhibition is critical to prevent thrombotic events in primary percutaneous coronary intervention (PCI). We aimed to determine the relationship between high on-treatment platelet reactivity (HTPR) and ST-elevation myocardial infarction (STEMI) following a 600 mg loading dose (LD) of clopidogrel. We performed a prospective monocentre study enrolling patients on clopidogrel undergoing PCI. The VASP index was used to assess PR inhibition after clopidogrel LD. HTPR was defined according to the consensus as a VASP index ≥50%. The present study included 833 patients undergoing PCI. Most patients had PCI for an acute coronary syndrome (58.7%). The mean VASP index was 50 ± 23% with a large inter-individual variability (range: 1-94%). Patients with a VASP index ≥50% were significantly older (p= 0.03), with a higher body mass index (BMI) (p<0.001), more often diabetic (p=0.03), taking omeprazole (p=0.03), admitted for an acute coronary syndrome (ACS) and with a high fibrinogen level compared to good responders (VASP <50%). In multivariate analysis BMI, omeprazole use, ACS and high fibrinogen level (p<0.001) remained significantly associated with HTPR. Of importance, in this analysis STEMI was independently associated with HTPR when compared with the other forms of ACS (NSTEMI and unstable angina) with an odd ratio of 2.14 (95% CI: 1.3 -3.5; p=0.003). In conclusion, STEMI is associated with high on-treatment platelet reactivity following 600 mg of clopidogrel. The present results suggest that 600 mg of clopidogrel may not be able to achieve an optimal PR inhibition in STEMI patients undergoing PCI and more potent drugs may be preferred.
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http://dx.doi.org/10.1160/TH12-02-0125DOI Listing
July 2012

Fall in oxygen tension of culture medium stimulates the adenosinergic signalling of a human T cell line.

Purinergic Signal 2012 Dec 14;8(4):661-7. Epub 2012 Feb 14.

UMR MD2 P2COE, Aix-Marseille Univ, Faculté de Médecine, Timone, 27, Boulevard Jean Moulin, F-13385, Marseille Cedex 5, France.

We examined the short-course expression of various parameters involved in the adenosinergic signalling of a human T cell line during in vitro decrease of the medium culture oxygen tension mimicking in vivo hypoxia. Fall of 92 mmHg in oxygen tension of culture medium induced in CEM, a CD4+ human T cell line, a continuous production of hypoxia-inducing factor-1α with a plateau value at 9 h, a rapid increase in adenosine production peaking at 3 h and a decrease in adenosine deaminase peaking at 6 h. The adenosine A(2A) receptor (A(2A)R) protein level of CEM cells was enhanced with a peak at 6 h. Intracellular 3',5'-cyclic adenosine monophosphate accumulated in CEM cells with a maximal level at 9 h. These results show that a human-cultured T cells line can upregulate its own adenosine production and A(2A)R expression during exposure to acute hypoxia. Hypoxia-increased stimulation of the adenosinergic signalling of T cells may have immunosuppressive properties and, consequently, A(2A)R agonists may have therapeutic relevance.
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http://dx.doi.org/10.1007/s11302-012-9295-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3486161PMC
December 2012

Short-term spirometric changes in wildland firefighters.

Am J Ind Med 2011 Nov 30;54(11):819-25. Epub 2011 Aug 30.

Centre Hospitalier Universitaire Timone Adultes, Pôle Réanimation, Urgences, SAMU and Hyperbarie, Marseille, France.

Background: The short-term effects of smoke inhalation have been little studied in European wildland firefighters, especially in an intra-individual design. Our purpose is to study the spirometric changes from the early stage during a wildland fire season and to compare smokers and non-smokers.

Methods: A population of 108 firefighters from a Civil Security Unit, based in Corsica, was tested immediately after having been exposed to the smoke of coniferous trees.

Results: Out of 108 people, 59 were smokers and 49 were non-smokers without any acute or chronic pulmonary disease. Compared to baseline values, a decrease of spirometric parameters was observed immediately after the end of exposure and an even greater decrease was seen after 24 hr (FEV1 -0.53 L; FVC -0.59 L; PEF -53 L min(-1), P < 0.05 for each). None of the participants complained of respiratory symptoms. Three months after the end of the season, a final test was given which revealed a persistent decrease in spirometric parameters in comparison with baseline values (FEV1 -0.28 L; FVC -0.34 L; PEF -45 L min(-1), P < 0.05 for each). Comparison of smoking and non-smoking groups did not show any noteworthy difference for each parameter or the importance of their decline.

Conclusions: The findings show that firefighters are likely to develop respiratory impairments after wood smoke exposure. We did not observe any statistical differences between smokers and non-smokers.
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http://dx.doi.org/10.1002/ajim.21002DOI Listing
November 2011

Rate of nuisance bleedings and impact on compliance to prasugrel in acute coronary syndromes.

Am J Cardiol 2011 Dec 8;108(12):1710-3. Epub 2011 Sep 8.

Département de Cardiologie, Hôpital Universitaire Nord, Faculté De Médecine, Université de la Méditerranée, Marseille, France.

Antiplatelet agents are critical to prevent thrombotic events in patients with acute coronary syndromes, particularly those who undergo percutaneous coronary intervention. Prasugrel is a potent P2Y(12)-adenosine diphosphate receptor antagonist that is superior to clopidogrel in such patients. Previous studies have observed that nuisance and internal bleedings were relatively frequent in patients under clopidogrel therapy and were associated with noncompliance. Furthermore, premature drug discontinuation is associated with thrombotic recurrences. The aim of the present study was to investigate the rate of nuisance or internal bleedings in patients receiving prasugrel and its relation with compliance. This prospective multicenter study included 396 patients. Bleeding events were recorded and classified as alarming, nuisance, or internal according. Compliance with prasugrel therapy was assessed. Almost half of the patients (48.5%) were included for ST-segment elevation acute coronary syndromes. During the 1-month follow-up period, 54 patients (13.6%) had bleeding events. Most bleeding events were classified as internal or nuisance (96%). Internal and nuisance bleedings were associated with high rates of prasugrel discontinuation (16.6% and 14.7%, respectively). Nuisance and internal bleedings were significantly associated with prasugrel discontinuation in multivariate analysis (odds ratio 3.1, 95% confidence interval 1.01 to 9.2, p = 0.04). The rate of major adverse cardiovascular events was 2.3%. No relation was observed between minor bleeds, compliance, and major adverse cardiovascular events. In conclusion, in the present study, minor bleedings were common during the first month after percutaneous coronary intervention and were significantly associated with prasugrel withdrawal.
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http://dx.doi.org/10.1016/j.amjcard.2011.07.038DOI Listing
December 2011

Personalized antiplatelet therapy: review of the latest clinical evidence.

Curr Cardiol Rep 2011 Aug;13(4):296-302

Service de Cardiologie, Hôpital de Martigues, Martigues, France.

P2Y12-ADP receptor antagonist use has been critical in the development of percutaneous coronary intervention, dramatically reducing the rate of early stent thrombosis. However, it recently was observed that a significant proportion of patients do not achieve optimal platelet reactivity inhibition after clopidogrel loading dose. The large interindividual variability in clopidogrel responsiveness is related to several factors, including the genetic polymorphism of hepatic cytochrome P450 2C19 (CYP2C19*2), which recently has been highlighted by a warning from the U.S. Food and Drug Administration. Of importance, patients exhibiting reduced clopidogrel metabolism and/or low clopidogrel responsiveness (ie, high on-treatment platelet reactivity) have an increased rate of thrombotic events after percutaneous coronary intervention. This review summarizes the current knowledge on this important clinical issue. While the future of genetic testing remains undetermined, several trials are underway to demonstrate the potential utility of platelet reactivity testing with P2Y12-ADP receptor antagonists.
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http://dx.doi.org/10.1007/s11886-011-0194-1DOI Listing
August 2011