Publications by authors named "Jacques Bessereau"

36 Publications

Early management of severe pelvic injury (first 24 hours).

Anaesth Crit Care Pain Med 2019 04 21;38(2):199-207. Epub 2018 Dec 21.

CHRU de Lille, réanimation chirurgicale, pôle d'anesthésie-réanimation, 2 avenue Oscar-Lambret 59037 Lille, France.

Objective: Pelvic fractures represent 5% of all traumatic fractures and 30% are isolated pelvic fractures. Pelvic fractures are found in 10 to 20% of severe trauma patients and their presence is highly correlated to increasing trauma severity scores. The high mortality of pelvic trauma, about 8 to 15%, is related to actively bleeding pelvic injuries and/or associated injuries to the head, abdomen or chest. Regardless of the severity of pelvic trauma, diagnosis and treatment must proceed according to a strategy that does not delay the management of the most severely injured patients. To date, in France, there are no guidelines issued by healthcare authorities or professional societies that address this subject.

Design: A consensus committee of 22 experts from the French Society of Anaesthesia and Intensive Care Medicine (Société Française d'Anesthésie et de Réanimation; SFAR) and the French Society of Emergency Medicine (Société Française de Médecine d'Urgence; SFMU) in collaboration with the French Society of Radiology (Société Française de Radiologie; SFR), French Defence Health Service (Service de Santé des Armées; SSA), French Society of Urology (Association Française d'Urologie; AFU), the French Society of Orthopaedic and Trauma Surgery (Société Française de Chirurgie Orthopédique et Traumatologique; SOCFCOT), and the French Society of Digestive Surgery (Société Française de Chirurgie digestive; SFCD) was convened. A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently from any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised.

Methods: Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. The analysis of the literature and the recommendations were then conducted according to the GRADE methodology.

Results: The SFAR Guideline panel provided 22 statements on prehospital and hospital management of the unstable patient with pelvic fracture. After three rounds of discussion and various amendments, a strong agreement was reached for 100% of recommendations. Of these recommendations, 11 have a high level of evidence (Grade 1 ± ), 11 have a low level of evidence (Grade 2 ± ).

Conclusions: Substantial agreement exists among experts regarding many strong recommendations for management of the unstable patient with pelvic fracture.
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http://dx.doi.org/10.1016/j.accpm.2018.12.003DOI Listing
April 2019

Safety of hyperbaric oxygen therapy in mechanically ventilated patients.

Int Marit Health 2017 ;68(1):46-51

Intensive Care Unit and Hyperbaric Department, CHU Raymond Poincaré, APHP, Garches, France Pôle RUSH, SAMU13, CHU La Timone, APHM, Marseille, France.

Background: To evaluate the epidemiology of patients who require mechanical ventilation during hyperbaric oxygen therapy.

Materials And Methods: One-hundred-fifty patients who required mechanical ventilation during hyperbaric oxygen therapy were prospectively studied during a 6-year period in a French university hyperbaric centre. We analysed the indication of hyperbaric oxygen therapy, agent used for sedation, presence of a chest tube, need for vasopressor agents and tolerance and appearance of side effects. Finally, we compared the outcomes of patients according to the presence or absence of acute respiratory distress syndrome (ARDS).

Results: Eleven children and 139 adult patients were included (n = 150) in the study. In both populations, carbon monoxide poisoning (51%) and iatrogenic gas embolism (33%) were the two main causes of intubation and mechanical ventilation. The combination of midazolam and sufentanil was used in 85 (67%) patients. All of the patients were given a bolus of a neuromuscular blocker during the hyperbaric session, despite the presence of ARDS in 35 patients. Patient-ventilator asynchrony was the most frequent side effect in 6 (5%) patients and was often the consequence of suboptimal sedation. Mortality was higher in the group with ARDS (23%).

Conclusions: Carbon monoxide poisoning and iatrogenic gas embolism are the two main diseases of the patients who required mechanical ventilation during hyperbaric oxygen therapy in this study. Mechanical ventilation is a safe method for patients during hyperbaric oxygen therapy. Sedation needs to be perfected to avoid patient-ventilator asynchrony.
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http://dx.doi.org/10.5603/IMH.2017.0008DOI Listing
September 2017

Epidemiology of unintentional drowning in a metropolis of the French Mediterranean coast: a retrospective analysis (2000-2011).

Int J Inj Contr Saf Promot 2016 Sep 17;23(3):317-22. Epub 2015 Jun 17.

a SAMU13, Pôle RUSH, CHU La Timone, AP-HM, Marseille, France.

Drowning affects more than 500,000 people worldwide and is responsible for at least 350,000 deaths each year. In France, 1235 drowning resulting in 496 deaths were recorded in the summer 2012. This retrospective study has investigated the epidemiology of drowning in the city of Marseille (South of France) between 2000 and 2011. We identified 449 cases of unintentional drowning. The highest incidence was found among males with a median age of 36 years. The incidence was 5.3 victims per 10,000 inhabitants with a mortality rate of 1.2 per 10,000. These accidents occurred mainly at sea (89%) and during the summer season. A majority of drowning victims (69%) were admitted in a hospital. This is the only study in France to analyse data on drowning throughout the year and over a long period. Drowning is a serious condition burdened by 22% of victims who die.
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http://dx.doi.org/10.1080/17457300.2015.1047862DOI Listing
September 2016

Perceived utility and limits of psychological interviews among French physicians and firefighter divers.

Int Marit Health 2015 ;66(1):55-6

SDIS du Vaucluse, Avignon, France; CUMP 13, Service de Psychiatrie, CHU La Conception, Marseille, France.

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http://dx.doi.org/10.5603/IMH.2015.0014DOI Listing
December 2015

Glossopharyngeal insufflation and breath-hold diving: the more, the worse?

Wilderness Environ Med 2014 Dec 14;25(4):466-71. Epub 2014 Oct 14.

UMR-MD2, French Armed Biomedical Research Institute, IRBA, Brétigny sur Orge, and Aix-Marseille University, Marseille, France (Drs Boussuges, Bessereau, Coulange, and Rossi); Internal Medicine Department, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Marseille, France (Dr Rossi).

Objective: The glossopharyngeal insufflation maneuver (lung packing) is largely performed by competitive breath-hold divers to improve their performance, despite observational evidence of fainting and loss of consciousness in the first seconds of apnea.

Methods: We describe here the time course of hemodynamic changes, induced by breath-holding with and without lung packing, in 2 world-class apnea competitors.

Results: When compared with apnea performed after a deep breath (100% vital capacity), lung packing leads to a decrease in cardiac output, blood pressure, and cerebral blood flow during the first seconds after the beginning of apnea. The major hemodynamic disorders were observed in diver 1, who exhibited the greater increase in pulmonary volume after lung packing (+22% for diver 1 vs +10% for diver 2). After the initial drop in both cardiac output and blood pressure, the time course of hemodynamic alterations became quite similar between the two apneas.

Conclusions: Some recommendations, such as limiting the number of maneuvers and performing lung packing in the supine position, should be expressed to avoid injuries secondary to the use of glossopharyngeal insufflation.
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http://dx.doi.org/10.1016/j.wem.2014.04.010DOI Listing
December 2014

COMparison of Platelet reactivity following prAsugrel and ticagrelor loading dose in ST-Segment elevation myocardial infarctION patients: The COMPASSION study.

Platelets 2015 2;26(6):570-2. Epub 2014 Oct 2.

Service de Cardiologie, Centre Hospitalo-Universitaire Nord, Assistance-Publique Hôpitaux de Marseille , Chemin des Bourrely, Marseille , France .

Prasugrel and ticagrelor are potent P2Y12-ADP receptor antagonists which are superior to clopidogrel in acute coronary syndromes. To date no clinical trial directly compared these two drugs. Platelet reactivity correlates with ischemic and bleeding events in patients undergoing percutaneous coronary intervention. Recent pharmacological studies have observed a delayed onset of action of these two drugs in ST-segment elevation myocardial infarction (STEMI). We provide the first adequately powered pharmacological study comparing PR following ticagrelor and prasugrel loading dose (LD) in STEMI patients when the maximal biological effect is reached. In the present study, ticagrelor was associated with a lower rate of high on-treatment PR compared to prasugrel.
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http://dx.doi.org/10.3109/09537104.2014.959914DOI Listing
May 2016

2-point ultrasonography to confirm correct position of the gastric tube in prehospital setting.

Mil Med 2014 Sep;179(9):959-63

Prehospital Emergency Medical Services of Marine Fire Battalion, Marseille, France.

Unlabelled: X-ray remains the "gold standard" test to control the gastric tube (GT) position. The aim of this study is to estimate the diagnostic accuracy of a 2-point ultrasonography to confirm GT placement in the prehospital setting.

Method: The emergency physician performed an ultrasound examination during GT insertion. The aim was to determine whether or not the GT could be viewed in the esophagus and/or in the stomach.

Results: Thirty-two intubated patients were included. In 100% of cases, the GT was instantly identified by ultrasound at esophagus and in 62.5% at stomach. In 6 cases, the GT was not seen in the stomach, but the injection of air through the GT allowed to confirm intragastric position in 2 cases. In the 4 other cases, no dynamic fogging was observed. In hospital X-ray control confirmed the correct positioning of 28/32.

Conclusion: The 2-point ultrasonographic live control of the GT position has a better sensitivity and a much higher specificity than the syringe test but similar to the xiphoid ultrasound control. However, our method allows to show the GT in the esophagus and to use the dynamic ultrasound fogging to reveal an intragastric position that was not obvious with the common techniques.
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http://dx.doi.org/10.7205/MILMED-D-14-00044DOI Listing
September 2014

Effect of ticagrelor-related dyspnea on compliance with therapy in acute coronary syndrome patients.

Int J Cardiol 2014 Apr 22;173(1):120-1. Epub 2014 Feb 22.

Département de Cardiologie Centre Hospitalo-Universitaire Nord, Aix-Marseille Univ., Marseille, France. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2014.02.028DOI Listing
April 2014

Prehospital ultrasound thoracic examination to improve decision making, triage, and care in blunt trauma.

Am J Emerg Med 2014 Jul 7;32(7):817.e1-2. Epub 2014 Jan 7.

Department of Emergency Medicine and Intensive Care, Timone University Hospital, Marseille, France.

Prehospital acute blunt thoracic trauma care remains difficult. Among then, diagnosis of atelectasis with ultrasound remains rare and unusual. We report the case of a worker who had a sharp chest pain currently after using a jackhammer. First clinical examination suspected a left tension pneumothorax but ruled out by sliding sign in left hemithorax ultrasound (US) examination. The right upper thoracic scan showed a well-defined lung point, a "hepatization" appearance with static air bronchograms, a diaphragm elevation and a dextrocardia in B mode, and a pseudobarcode with no lung pulse in Time Motion (TM) mode. A "rip's organ absent sign" excluded the hypothesis of an acute diaphragmatic rupture. An atelectasis was at once suspected and confirmed at hospital by tomodensitometry. Diaphragmatic injury can be suspected when "rip's absent organ sign," diaphragm poor movement or elevation, liver sliding sign, subphrenic effusion, or spleen or liver intrathoracic presence. Unusually, these signs can put diagnosis in a wrong track as described in our case report. Lung pulse, absent sliding sign, or hemidiaphragm standstill is highly suspect of atelectasis but cannot be established formally. However, in patients with alveolar consolidation displaying air bronchograms, the dynamic air bronchograms indicated lung contusion, distinguishing it from atelectasis. Static air bronchograms were seen in most atelectases and one-third of cases of contusion or pneumonia. Fast scan can be useful to evoke atelectasis in blunt trauma. Differential diagnoses such as diaphragmatic rupture or consolidation could be discarded. Ultrasound examination could justify a precise semiological description.
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http://dx.doi.org/10.1016/j.ajem.2013.12.063DOI Listing
July 2014

Stay and play eFAST or scoop and run eFAST? That is the question!

Am J Emerg Med 2014 Feb 12;32(2):166-70. Epub 2013 Nov 12.

Department of Emergency Medicine and Intensive Care, HIA Desgenettes, Lyon, France.

Unlabelled: The concept that ultrasonography could be interesting in the prehospital setting and during the transfer of traumatized patients is not new. Paradoxically, there is a lack of description of routine use of ultrasonography in emergency ambulances. The aim of this study was to compare the feasibility and efficiency of an extended focused assessment sonography for trauma (eFAST) examination performed on-site, during the patient's transfer, or both.

Materials And Methods: From February 2010 to June 2012, 30 prehospital emergency physicians were divided randomly into 3 groups. Group 1 performed an ultrasound examination on-site; group 2, during patient transfer; and group 3, in both settings. The eFAST examination was systematically performed in all severe traumas.

Results: Ninety-eight patients were included. Forty-four eFAST examinations were performed on-site only; 33, only during transport; and 21, in both settings. The feasibility was 95.4%, 93.9%, and 95.2%, respectively, and efficiency, 95%, 97%, and 100%, respectively. There was no significant difference in performance or duration whether the examination was performed on-site, during the transfer, or both (w = 0.68). Last but not least, in 2 cases in group 3, the second examination carried out during transfer showed new results with the occurrence of intraperitoneal effusion in one case and a pleural effusion in the other.

Conclusions: The eFAST examination can provide reliable and important information in the initial evaluation of traumatized patients. It can be completed either on-site or during patient transfer. Its feasibility and efficiency are similar to that done in intensive units, especially if the examination is repeated.
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http://dx.doi.org/10.1016/j.ajem.2013.11.008DOI Listing
February 2014

Ticagrelor versus prasugrel in diabetic patients with an acute coronary syndrome. A pharmacodynamic randomised study.

Thromb Haemost 2014 Feb 24;111(2):273-8. Epub 2013 Oct 24.

Laurent Bonello, MD, PhD, Department of cardiology, Hôpital universitaire nord, Chemin des bourrely, 13015 Marseille, France, Tel.: +33 491 968 858, Fax: +33 491 968 979, E-mail:

Optimal P2Y12 receptor blockade is critical to prevent ischaemic recurrence in patients undergoing percutaneous coronary intervention (PCI). We aimed to compare the level of platelet reactivity (PR) inhibition achieved by prasugrel and ticagrelor loading dose (LD) in diabetic acute coronary syndrome (ACS) patients undergoing PCI. We performed a single-center prospective open-label randomised trial. Patients with diabetes mellitus undergoing PCI for an ACS were randomised to receive prasugrel 60 mg or ticagrelor 180 mg. The primary endpoint of the study was the level of platelet reactivity (PR) assessed between 6 and 18 hours post-LD using the VASP index. We randomised 100 diabetic patients undergoing PCI for an ACS. No difference was observed in baseline characteristics between the two groups. In particular, the rate of patient receiving insulin therapy was identical (25 vs 28.6%; p =0.7). Ticagrelor achieved a significantly lower PR compared to prasugrel loading dose (17.3 ± 14.2 vs 27.7 ± 23.3%; p=0.009). In addition the rate of high on-treatment platelet reactivity, defined by a VASP ≥50%, tend to be lower in the ticagrelor group although the difference did not reach statistical significance (6 vs 16%; p=0.2). The rate of low on treatment PR was identical (60 vs 54%; p=0.8). The present study demonstrates that ticagrelor LD is superior to prasugrel LD to reduce PR in ACS patients with diabetes mellitus. Whether the higher potency of ticagrelor could translate into a clinical benefit should be investigated.
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http://dx.doi.org/10.1160/TH13-05-0384DOI Listing
February 2014

Response to letter to the editor by Westerweel et al., entitled 'aspirin in the treatment of decompression sickness: what can we learn from French experience?' [Int Marit Health 2013; 64, 1: 51].

Int Marit Health 2013 ;64(3):175

Intensive Care Unit and Hyperbaric Department, Raymond Poincaré Teaching Hospital, Garches, France.

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May 2014

Assessing post-treatment platelet reactivity: a focus on patient selection and setting.

Expert Rev Cardiovasc Ther 2013 Nov 2;11(11):1557-66. Epub 2013 Sep 2.

Département de Cardiologie, Hôpital Universitaire Nord, Marseille, France.

Dual antiplatelet therapy is critical to inhibit platelet reactivity in order to prevent ischemic recurrences in stented patients. However, studies have observed a variable blockade of the P2Y12 adenosine diphosphate receptor between patients following clopidogrel intake. This interindividual variability in the biological response is not uncommon with clopidogrel (about 50%) and even prasugrel (20%). High on-treatment platelet reactivity (HTPR) is correlated with thrombotic events following percutaneous coronary intervention. Several studies suggested that tailoring of antiplatelet therapy based on platelet reactivity (PR) monitoring could safely reduce the rate of major adverse cardiovascular events in HTPR patients. In addition, low on-treatment PR was recently associated with bleeding events both in patients treated with prasugrel and clopidogrel. Of importance, bleedings are associated with a poor prognosis in stented patients. Overall, the potential of PR monitoring to individualize antiplatelet therapy might benefit stented patients by reducing both ischemic and bleeding risks. However, such strategies remain to be evaluated in adequately designed large-scale randomized clinical trials.
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http://dx.doi.org/10.1586/14779072.2013.820440DOI Listing
November 2013

A randomized trial of platelet reactivity monitoring-adjusted clopidogrel therapy versus prasugrel therapy to reduce high on-treatment platelet reactivity.

Int J Cardiol 2013 Oct 2;168(4):4244-8. Epub 2013 Aug 2.

Département de cardiologie, Hôpital universitaire nord, Aix-Marseille Univ., Marseille, France; INSERM UMRS 608, UFR de pharmacie, Marseille, France. Electronic address:

Background: Peri-procedural platelet reactivity (PR) inhibition is critical in patients undergoing percutaneous coronary intervention (PCI). High on-treatment PR (HTPR) was associated with recurrent ischemic events in acute coronary syndrome (ACS) patients undergoing PCI. We aimed to compare a strategy of clopidogrel loading dose-adjustment (CDA) according to PR monitoring with standard prasugrel therapy to reduce the rate of patients exhibiting HTPR.

Methods: We enrolled 177 ACS patients in a prospective multicentre randomized trial comparing CDA according to PR monitoring and prasugrel therapy. The VASP index was used to measure PR and a VASP ≥ 50% defined HTPR. The primary endpoint of the study was the rate of HTPR on discharge.

Results: Baseline characteristics of the CDA group (n = 88) and of the prasugrel group (n = 89) were similar. CDA significantly reduced PR and the rate of HTPR compared to a single LD of clopidogrel (30.9 ± 13.9%; p < 0.0001 and 43 to 2.3%; p < 0.001, respectively). Following CDA the rate of patients with HTPR was significantly lower in the CDA group compared to the prasugrel group on discharge (2.3 vs 15.7%; p = 0.005). In addition fewer patients in the CDA group had a VASP < 16% on discharge (14.7 vs 50.5%; p <0.0001).

Conclusion: In the present study, PR monitoring was superior to standard prasugrel therapy to reduce the rate of HTPR in ACS patients. In addition such strategy reduced the number of patients with very low PR.
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http://dx.doi.org/10.1016/j.ijcard.2013.07.147DOI Listing
October 2013

Platelet reactivity evaluated with the VASP assay following ticagrelor loading dose in acute coronary syndrome patients undergoing percutaneous coronary intervention.

Thromb Res 2013 Jul 30;132(1):e15-8. Epub 2013 May 30.

Département de cardiologie, Hôpital universitaire nord, Aix-Marseille Univ., Marseille, France.

Background: The level of platelet reactivity (PR) inhibition obtained after P2Y12-ADP receptor antagonist loading dose (LD) is associated with the ischemic and bleeding risk following percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS).

Objective: We aimed to evaluate the level of PR inhibition achieved by a 180 mg LD of ticagrelor and the rate of high on-treatment platelet reactivity (HTPR) in ACS patients undergoing PCI.

Methods: We performed a multicentre prospective observational study enrolling ACS patients undergoing PCI. Patients were included if they were admitted for ST-elevation myocardial infarction or non ST-elevation ACS. To assess PR, a VASP index was measured at least 6 and within 24 hours following a 180 mg LD of ticagrelor. HTPR was defined as a VASP index ≥50%.

Results: One hundred and fifteen patients were included: 31.3% of STEMI, 49.6% of NSTEMI and 19.1% of unstable angina. Following ticagrelor LD the mean VASP index was 17±14%. However the response to ticagrelor was not uniform with a small inter-individual variability: inter quartile range: 7.6-22.8% and a rate of HTPR of 3.5%. A high number of patients, 65.6%, had a VASP index <16%. None of the baseline characteristics of the study population was associated with PR. In addition, PR was similar in STEMI, NSTEMI and unstable angina (p=0.9).

Conclusion: In ACS patients the level of PR inhibition achieved by a 180 mg loading dose of ticagrelor is not uniform and the rate of HTPR is 3.5%. A high proportion of patients exhibited a VASP index <16%.
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http://dx.doi.org/10.1016/j.thromres.2013.04.030DOI Listing
July 2013

Decompression sickness in urban divers in France.

Int Marit Health 2012 ;63(3):170-3

General Intensive Care Unit, Hyperbaric Medicine Department, Raymond Poincaré Hospital, University of Versailles SQY, Garches, France.

Background: Decompression sickness (DCS) can occur in SCUBA divers. DCS is treated with oxygen, preferably given under hyperbaric conditions. Although Paris (France) is located at a distance from the sea or lakes, some injured divers require hyperbaric oxygen treatment (HBOT) in this city, sometimes within a specific time frame. Thus, this study investigated the epidemiology and outcomes of such urban divers.

Aim: We conducted an observational study of SCUBA divers admitted to the Raymond Poincaré Hyperbaric centre near Paris from 1993 to 2003.

Materials And Methods: We prospectively enrolled 69 consecutive SCUBA divers presenting DCS. Common risk factors were reported, especially aeroplane flight and training dives. Symptoms are very often atypical (63%) and onset time of symptoms is often too long (59% after 2 h) due to denial of symptoms. First aid is generally inadequate, with only 23% of victims receiving oxygen, fluid loading and aspirin together. HBOT was given for 42 (61%) patients although their examination results were considered as normal.

Conclusions: Diving pits and diving travel agencies should do more to warn divers of the need for treatment with normobaric oxygen and hydration pending HBOT. Moreover, hyperbaric physicians should better clarify HBOT indications for both symptoms of late onset and atypical presentations.
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April 2013

Tailoring antiplatelet therapy: a step toward individualized therapy to improve clinical outcome?

Curr Pharm Des 2012 ;18(33):5392-401

Département de cardiologie, Hopital universtaire nord de Marseille, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille univ. France, Marseille, France.

P2Y12 adenosine di-phosphate (ADP) receptor antagonists are critical to reduce thrombotic recurrences in acute coronary syndromes patients and for those undergoing percutaneous coronary revascularization. Multiple lines of evidence suggest that the level of on-treatment platelet reactivity inhibition with P2Y12 ADP receptor antagonists correlates with thrombotic recurrences. Recent studies observed a relationship between excessive platelet reactivity inhibition and bleedings. Together these data support the potential of platelet reactivity measurement to prevent thrombotic events without increasing bleeding. In the present review we aimed to summarize evidences of a therapeutic window for P2Y12-ADP receptor antagonists and the potential of platelet reactivity monitoring and individualized antiplatelet therapy to optimize the clinical outcome in patients suffering from an acute coronary syndrome or undergoing percutaneous coronary intervention.
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http://dx.doi.org/10.2174/138161212803251934DOI Listing
April 2013

Latest evidence in personalized antiplatelet therapy in patients with acute coronary syndromes undergoing percutaneous coronary intervention.

Hosp Pract (1995) 2012 Apr;40(2):104-17

Département de Cardiologie, Hôpital Universitaire Nord de Marseille, Assistance Publique Hôpitaux de Marseille, Aix-Marseille Université, France.

In patients with acute coronary syndromes undergoing percutaneous coronary intervention, the combination of aspirin and clopidogrel, a P2Y12 adenosine diphosphate (ADP) receptor antagonist, is the gold standard of antiplatelet therapy. Two more potent P2Y12 ADP receptor antagonists are now available. Pharmacodynamic studies have revealed a large interindividual variability in the biological response to clopidogrel that is primarily related to variable active metabolite generation, depending on clinical factors, drug-drug interactions, and genetic polymorphisms. Several assays to measure platelet function are available and have revealed a high prevalence of high on-treatment platelet reactivity (HTPR). Patients exhibiting HTPR after a clopidogrel loading dose have a higher risk of thrombotic recurrence after percutaneous coronary intervention. A recent consensus has defined HTPR for the main platelet assays available (using receiver operating characteristic curve analysis) to define the optimal cutoff value for each assay in order to predict thrombotic recurrences. In this article, we present several lines of evidence that suggest a therapeutic window of platelet reactivity inhibition with P2Y12 ADP receptor antagonists. Such a paradigm shift is supported by the results of the Platelet Inhibition and Patient Outcomes (PLATO) trial and the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38, which showed the superiority of ticagrelor and prasugrel on thrombotic events compared with clopidogrel; however, these 2 medications had an increased bleeding rate. With the results of these trials, in addition to the evidence of a therapeutic window with P2Y12 ADP receptor antagonists, we summarize the potential of platelet reactivity monitoring and pharmacogenomics to tailor therapy.
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http://dx.doi.org/10.3810/hp.2012.04.976DOI Listing
April 2012

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

Factors associated with the failure of clopidogrel dose-adjustment according to platelet reactivity monitoring to optimize P2Y12-ADP receptor blockade.

Thromb Res 2012 Jul 27;130(1):70-4. Epub 2012 Jan 27.

Département de cardiologie, Hôpital Universitaire Nord, Faculté de médecine, Aix-Marseille université, Marseille, France.

Introduction: Inter-individual variability in clopidogrel responsiveness is dependent on genetic polymorphisms. We aimed to investigate the impact of 3 genetic polymorphisms involved in clopidogrel metabolism on a strategy of dose-adjustment according to platelet reactivity (PR) monitoring.

Material And Methods: [corrected] This prospective multicenter study enrolled 498 ACS patients undergoing PCI. PR was measured using the Vasodilator-Stimulated Phosphoprotein index (VASP) and a cut-off value of ≥50% defined high on-treatment platelet reactivity (HTPR). Genetic polymorphisms of cytochrome (CYP) 2C19, Paraxonase-1 (PON1) and ABCB1 were determined by allele specific PCR. Dose-adjustment was performed using up-to 3 additional loading doses (LD) of 600mg clopidogrel in order to obtain a VASP <50% in patients with HTPR following the first LD.

Results: CYP 2C19 2*polymorphism (p=0.02), but neither PON1 (p=0.8) nor ABCB1 genotype (p=0.9), was significantly associated with HTPR. The dose-adjustment strategy failed in 11% of patients. ABCB1 polymorphism was significantly associated with a failed dose-adjustment (FDA) (p=0.04). No relation was found between the other genotypes and the efficacy of LD adjustment. In multivariate analysis, BMI and ABCB1 polymorphism were the only factors significantly associated with FDA (p=0.005 and p=0.04 respectively).

Conclusion: While CYP 2C19 2* is associated with HTPR after 600mg of clopidogrel, ABCB1 is responsible for the failure of a strategy of loading dose-adjustment according to PR monitoring. These findings may help to define a therapeutic strategy to optimize anti-platelet therapy in ACS patients undergoing PCI.
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http://dx.doi.org/10.1016/j.thromres.2011.12.038DOI Listing
July 2012

Ultrasound to confirm gastric tube placement in prehospital management.

Resuscitation 2012 Apr 29;83(4):447-51. Epub 2011 Dec 29.

Department of Emergency Medicine and Radiology, Clavary General Hospital, Grasse, France.

Background: In emergency medicine, the gastric tube (GT) has many purposes, however in prehospital settings, the only indication is gastric decompression. To date, there is lack of recommendation on the diagnostic methods to verify correct GT placement in prehospital. The aim of this study is to estimate diagnostic accuracy of ultrasound in confirming gastric tubes placement in a prehospital setting.

Method: This was a prospective multicentre study conducted in two French towns (Marseille and Grasse) over a one-year period from May 2010 to May 2011.

Results: One hundred and thirty patients were included in the study with an M/F sex ratio of 77/53 and a mean age of 55.7±19.8 years. The GT position was confirmed by ultrasound, with direct visualization in the gastric area in 116 of the 130 patients. In 14 cases, the ultrasound failed to visualize the tip of the GT; these results were due in 2 cases to gas interposition and in 12 cases the GT was shown by final X-ray to be located in the end of the oesophagus. Direct visualization by ultrasound thus has a sensitivity of 98.3% [94-99.5] and a specificity of 100% [75.7-100], a positive predictive value of 100% and a negative predictive value of 85.7%, Youden's index of 0.98. GT size affects ultrasound visualization; the larger the GT, the easier it is to see.

Conclusion: Bedside ultrasound thus appears to constitute an effective and reliable diagnostic procedure for confirming correct gastric tube placement in prehospital settings.
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http://dx.doi.org/10.1016/j.resuscitation.2011.11.035DOI Listing
April 2012

Lung ultrasound associated to capnography to verify correct endotracheal tube positioning in prehospital.

Am J Emerg Med 2012 Nov 26;30(9):2080.e5-6. Epub 2011 Dec 26.

Prehospital Emergency Medical Services of Marine Fire Battalion, Marseille, France.

Endotracheal intubation is the “gold standard” of the control of airway patency but is associated with nonnegligible morbidity rates. A rapid detection of esophageal intubation is essential. Capnography is considered the reference technique for correct endotracheal tube (ETT) positioning confirmation. However, capnography can provide false-positive and false-negative results in some situations. Recently, the ultrasound assessment has been studied for confirming ETT placement. Despite of few trials, the ultrasound procedure may enhance physician confidence and decision making in airway management. We report the case of a 52-year-old female patient presenting cardiorespiratory failure. During cardiopulmonary resuscitation, there was a sudden absence of end-tidal CO2 capnographic detection. Correct tube positioning could not be ascertained by auscultation because the environment had become extremely noisy. However, TM-mode (Time Motion--mode) lung ultrasound revealed bilateral pleural sliding during insufflation with the self-filling balloon, thus confirming correct ETT positioning.
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http://dx.doi.org/10.1016/j.ajem.2011.10.023DOI Listing
November 2012

[Pandemic influenza A (H1N1 virus) on Futuna Island in the Pacific, from August to September 2009].

Presse Med 2011 Mar 19;40(3):e145-51. Epub 2011 Jan 19.

Centre hospitalier universitaire Timone, service d'aide médicale d'urgence (SAMU 13), 13385 Marseille cedex 05, France.

Objective: The aim of this study is to report the observation of the pandemic of influenza A (H1N1 virus) from August to September 2009 on the island of Futuna, in a context of isolated island that may mimic an environment closed.

Method: We conducted a prospective observational study of influenza-like illness, from the first confirmed case of influenza A on the island until the end of the epidemic wave.

Results: From August 15 to September 20, 2009, 1536 cases of influenza syndrome were identified. The estimate of the overall clinical attack rate was 36 %. The evolution of the epidemic shows an explosion of new cases of influenza A and subsequently a rapid decline of the epidemic. The spread of the infection was made by contiguity, jumping from one city to another. The cumulative number of cases by age group shows that the majority of cases were children and young adults under the age of 20 years. The most frequent symptoms were cough, rhinorrhea, headache, myalgia or asthenia, and fever.

Conclusion: This study, despite these limitations, shows an explosive epidemic of influenza A, which can be explained by the circulation of virus that has been fostered by gatherings of public and closed environment. Age group classification shows that majority of cases were young, in contrast to seasonal influenza, but the symptoms were alike. This study highlights the difficulties to manage an epidemic surveillance system at high level and given the quick spread of the disease.
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http://dx.doi.org/10.1016/j.lpm.2010.10.019DOI Listing
March 2011