Philippe JEAN-PIERRE

---

• Type de publi. : Communication dans un congrès
• Date de publi. : 03/07/2023
• Auteurs : Julien RouzotChristian ArtiguesPhilippe GarnierEmmanuel HebrardPierre Lopez
• Organismes : Équipe Recherche Opérationnelle, Optimisation Combinatoire et Contraintes Institut de recherche en astrophysique et planétologie Équipe Recherche Opérationnelle, Optimisation Combinatoire et Contraintes Institut de recherche en astrophysique et planétologie Institut Universitaire de Technologie - Paul Sabatier Équipe Recherche Opérationnelle, Optimisation Combinatoire et Contraintes Équipe Recherche Opérationnelle, Optimisation Combinatoire et Contraintes

---

Résumé : Dans le cadre des missions spatiales où les ressources à bord sont limitées, il est essentiel de transférer les données acquises de manière efficace afin de limiter le risque de saturation des mémoires. Nous nous intéressons ici en particulier à l'ordonnancement des transferts de données de la mission Rosetta de l'ESA (l'agence spatiale européenne). Ce problème a été résolu par des méthodes heuristiques qui ont donné de bons résultats, voire des résultats optimaux dans certains cas. Dans la lignée d'un travail précédent, nous proposons dans cet article un modèle de programmation par contraintes pour résoudre exactement ce problème, nous proposons une nouvelle contrainte globale pour le partage de bande passante en fonction de priorités, ainsi qu'une contrainte globale pour les classements de type Dense Ranking. Des premiers résultats montrent la pertinence et l'efficacité d'une telle approche exacte pour la résolution de ce problème. Un des buts dans la conception de ces contraintes est leur généricité, afin qu'elles puissent être appliquées à toute mission spatiale nécessitant des transferts de données, ainsi qu'à tout problème nécessitant un classement Dense Ranking.

---

Fichiers liés : Une_contrainte_globale_pour_l_ordonnancement_des_transferts_de_données_dans_les_missions_spatiales (JFPC 2023).pdf

---

Source

---

• Type de publi. : Communication dans un congrès
• Date de publi. : 02/07/2023
• Auteurs : Pierre GrimaudFabrice PetitLaurent BoiletMarie LasgorceixFlorian JeanAnne LerichePascal LaurentPhilippe Champagne
• Organismes : Université Polytechnique Hauts-de-France INSA Institut National des Sciences Appliquées Hauts-de-France Laboratoire de Matériaux Céramiques et de Mathématiques Science des Procédés Céramiques et de Traitements de Surface

---

Résumé : Dental crowns are among the modern tools used in dentistry to restore physiological function such as phonation or mastication. They are currently mainly manufactured by machining pre-sintered disk but this technique has some drawbacks such as risks of damage to the part or some geometric limitations. To overcome this drawback some alternative techniques have been studied such as LASER machining, stereolithography (SLA) or selective LASER melting (SLM). But these alternative methods also suffer from defects and are therefore little used. This work is therefore part of a kind of continuity by exploring a new shaping method for dental crowns. In this project, two different techniques are combined, the first one is polymer stereolithography which is used to produce complex molds and the latter one is gel casting which is a process commonly used for producing parts with complex geometries. It was initially developed to overcome the limitations of other shaping processes such as injection molding or machining. Designed by Janney & Omatete in 1991, this process is very versatile, both in terms of its compatibility with different classes of materials and its compatibility with different molds manufacturing techniques. In practice, gel casting is based on the production of a slurry in an aqueous medium in the presence of a dispersant and a gelling agent. The slurry is poured into a mold where gelation can occur and form a three-dimensional network that ensures shape retention and maintenance of homogeneity within the part. A wide range of gelling agents can be used for gel casting with different families such as synthetic polymers, proteins or polysaccharides. This study is more focused on bio-sourced products and more specifically on the polysaccharide type. Two of them were selected: agarose and sodium alginate they have different gelling mechanisms which means two different gel casting processes. The presentation is more focused on formulations, processes, and whole characterisation of the parts.

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 01/07/2023
• Auteurs : Philippe AzouviMarc RousseauxPaolo BartolomeoDominic Alain PérennouPascale Pradat-DiehlLaurent WiartGilles RodeOlivier Godefroy
• Organismes : Service de réeducation fonctionnelle [Raymond Poincaré] Centre de recherche en épidémiologie et santé des populations Service de rééducation neurologique [Hôpital Pierre Swynghedauw - Lille] CHU de Grenoble-Alpes - Centre Hospitalier Universitaire CHU Grenoble Laboratoire de Psychologie et NeuroCognition Service de médecine physique et de réadaptation neurologique [Lyon] Université Claude Bernard Lyon 1 Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center CHU Amiens-Picardie Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559
• Publié dans European Journal of Neurology le 22/10/2020

---

Résumé : Objective: To assess the most sensitive combination of tests to detect peri-personal unilateral neglect (UN) after stroke. Methods: The present study is a secondary analysis of a previously reported multicentric study of 203 individuals with right hemisphere damage (RHD), mainly subacute stroke, 11 weeks post onset on average, and 307 healthy controls. A battery of 7 tests, providing 19 age and education adjusted z scores were given: the bells test, line bisection, figure copying, clock drawing, overlapping figures test, reading and writing. Statistical analyses used a logistic regression and a ROC after adjustment on demographic variables. Results: A combination of 4 z-scores based on the following three tests provided a good discrimination of patients with RHD from matched healthy controls: the starting point and the difference between the number of omissions on left and right sides from the Bells test, rightward deviation in bisection of long lines (20 cm), and left-sided omissions in a reading task. The area under the ROC curve was 0.865 (95%CI: 0.83-0.901) with a sensitivity= 0.68; a specificity = 0.95, an accuracy =0.85, a PPV= 0.90, and a NPV=0.82. Discussion / conclusion: The most sensitive and parsimonious combination of tests to detect UN after stroke relies on 4 scores from 3 simple tests (bells test, line bisection and reading). Future study is warranted to assess its ability to account for the functional difficulties of UN in daily life in the patient's actual environment.

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 01/07/2023
• Auteurs : Sophie HubyPhilippe GelisseJean-Jacques TudesqPierre M. LabaugeClaire DuflosClaire DuflosGuillaume CartronMarc-Antoine GallerandLaura PlatonStéphanie BadiouSylvain LamureNicolas Menjot de ChampfleurXavier AyrignacGuillaume Taieb
• Organismes : Centre Hospitalier Régional Universitaire [Montpellier] Centre Hospitalier Régional Universitaire [Montpellier] Centre Hospitalier Régional Universitaire [Montpellier] Université de Montpellier Centre Hospitalier Régional Universitaire [Montpellier] Université de Montpellier Centre Hospitalier Régional Universitaire [Montpellier] Centre Hospitalier Régional Universitaire [Montpellier] Institut Desbrest d'Epidémiologie et de Santé Publique Institut de Génétique Moléculaire de Montpellier Centre Hospitalier Régional Universitaire [Montpellier] Centre Hospitalier Régional Universitaire [Montpellier] Centre Hospitalier Régional Universitaire [Montpellier] Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] Centre Hospitalier Régional Universitaire [Montpellier] Centre Hospitalier Régional Universitaire [Montpellier] Institut de Génétique Moléculaire de Montpellier Centre Hospitalier Régional Universitaire [Montpellier] Laboratoire Charles Coulomb Centre Hospitalier Régional Universitaire [Montpellier] Institut des Neurosciences de Montpellier Centre Hospitalier Régional Universitaire [Montpellier] Institut de Génomique Fonctionnelle
• Publié dans Neurology Neuroimmunology & Neuroinflammation le 28/10/2020

---

Résumé : Background and objectives: Chimeric antigen receptor (CAR) T-cell therapies have dramatically improved the prognosis of patients with relapsed or refractory hematologic malignancies; however, cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS) occur in ∼100 and 50% of patients, respectively. This study aimed to determine whether EEG patterns may be considered as diagnostic tools for ICANS. Methods: Patients who received CAR T-cell therapy at Montpellier University Hospital between September 2020 and July 2021 were prospectively enrolled. Neurologic signs/symptoms and laboratory parameters were monitored daily for 14 days after CAR T-cell infusion. EEG and brain MRI were performed between day 6 and 8 after CAR T-cell infusion. EEG was performed again on the day of ICANS occurrence, if outside this time window. All collected data were compared between patients with and without ICANS. Results: Thirty-eight consecutive patients were enrolled (14 women; median age: 65 years, interquartile range: [55-74]). ICANS was observed in 17 of 38 patients (44%) after a median time of 6 days after CAR T-cell infusion (4-8). The median ICANS grade was 2 (1-3). Higher C-reactive protein peak (146 mg/L [86-256], p = 0.004) at day 4 (3-6), lower natremia (131 mmol/L [129-132], p = 0.005) at day 5 (3-6), and frontal intermittent rhythmic delta activity (FIRDA, p < 0.001) on EEG between days 6 and 8 after infusion were correlated with ICANS occurrence. FIRDA was only observed in patients with ICANS (N = 15/17, sensitivity of 88%) and disappeared after ICANS resolution, usually after steroid therapy. Except for hyponatremia, no other toxic/metabolic marker was associated with FIRDA (p = 0.002). The plasma concentration of copeptin, a surrogate marker of antidiuretic hormone secretion, assessed at day 7 after infusion, was significantly higher in patients with (N = 8) than without (N = 6) ICANS (p = 0.043). Discussion: FIRDA is a reliable diagnostic tool for ICANS, with a sensitivity of 88% and a negative predictive value of 100%. Moreover, as this EEG pattern disappeared concomitantly with ICANS resolution, FIRDA could be used to monitor neurotoxicity. Finally, our study suggests a pathogenic pathway that starts with increased C-reactive protein, followed by hyponatremia and eventually ICANS and FIRDA. More studies are required to confirm our results. Classification of evidence: This study provides Class III evidence that FIRDA on spot EEG accurately distinguishes patients with ICANS compared with those without after CAR T-cell therapy for hematologic malignancy.

---

Fichiers liés : e200111.full.pdf

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 01/07/2023
• Auteurs : Jean-Philippe Duvel
• Organismes : Laboratoire de Météorologie Dynamique (UMR 8539)
• Publié dans Monthly Weather Review le 28/10/2020

---

Résumé : Abstract Numerous low-level vortices are initiated downwind of the Hoggar Mountains and progress toward the Atlantic coast on the northern path of African easterly waves (AEWs). These vortices occur mostly in July and August and more specifically when the northern position of the Saharan heat low (SHL) generates stronger and vertically expanded easterly winds over the Hoggar Mountains. At synoptic time scales, a composite analysis reveals that vortex initiation and westward motion are also statistically triggered by a reinforcement of these easterly winds by a wide and persistent high pressure anomaly developing around the Strait of Gibraltar and by a weak wave trough approaching from the east. The vortices are generated in the lee of the Hoggar, about 1000 km west of this approaching trough, and intensify rapidly. The evolution of the vortex perturbation is afterward comparable with the known evolution of the AEWs of the northern path and suggest a growth due to dry barotropic and baroclinic processes induced in particular by the strong cyclonic shear between the reinforced easterly winds and the monsoon flow. These results show that vortex genesis promoted by changes in orographic forcing due to the strengthening of easterly winds over the Hoggar Mountains is a source of intensification of the northern path of AEWs in July and August. These results also provide a possible mechanism to explain the role of the SHL and of particular midlatitude intraseasonal disturbances on the intensity of these waves.

---

Fichiers liés : ARTICLE_DUVEL_HOGGAR_Rev4.pdf

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 01/07/2023
• Auteurs : Cyril LibourelJean KellerLukas BrichetAnne-Claire Cazale-NoelSébastien CarrereTatiana VerniéJean-Malo CouzigouCaroline CallotIsabelle DufauStephane CauetWilliam MarandeTabatha BulachAmandine SuinCatherine MassonPhilippe RemigiPierre-Marc DelauxDelphine Capela
• Organismes : Laboratoire de Recherche en Sciences Végétales Laboratoire de Recherche en Sciences Végétales Laboratoire des Interactions Plantes Microbes Environnement Laboratoire des Interactions Plantes Microbes Environnement Laboratoire des Interactions Plantes Microbes Environnement Laboratoire de Recherche en Sciences Végétales LRSV-Interactions Microbiennes dans la Rhizosphère et les Racines Centre National de Ressources Génomiques Végétales Centre National de Ressources Génomiques Végétales Centre National de Ressources Génomiques Végétales Centre National de Ressources Génomiques Végétales Génome et Transcriptome - Plateforme Génomique Génome et Transcriptome - Plateforme Génomique Laboratoire des Interactions Plantes Microbes Environnement Laboratoire des Interactions Plantes Microbes Environnement LRSV-Evolution des Interactions Plantes-Microorganismes Laboratoire des Interactions Plantes Microbes Environnement
• Publié dans Nature Plants le 21/10/2020

---

Résumé : Abstract Symbiotic interactions such as the nitrogen-fixing root nodule symbiosis (RNS) have structured ecosystems during the evolution of life. Here we aimed at reconstructing ancestral and intermediate steps that shaped RNS observed in extant flowering plants. We compared the symbiotic transcriptomic responses of nine host plants, including the mimosoid legume Mimosa pudica for which we assembled a chromosome-level genome. We reconstructed the ancestral RNS transcriptome composed of most known symbiotic genes together with hundreds of novel candidates. Cross-referencing with transcriptomic data in response to experimentally evolved bacterial strains with gradual symbiotic proficiencies, we found the response to bacterial signals, nodule infection, nodule organogenesis and nitrogen fixation to be ancestral. By contrast, the release of symbiosomes was associated with recently evolved genes encoding small proteins in each lineage. We demonstrate that the symbiotic response was mostly in place in the most recent common ancestor of the RNS-forming species more than 90 million years ago.

---

Fichiers liés : Libourel cnrgv 2023.pdf

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 01/07/2023
• Auteurs : Thi Loi Daovan Thuan HoangAmal MagmounTran Duc Anh LySophie Alexandra BaronLinda HadjadjNaomie CanardTassadit DraliFrédérique GourietDidier RaoultPhilippe ParolaPierre MartyJean-Marc RolainPhilippe Gautret
• Organismes : Thai Binh University of Medecine and Pharmacy Vecteurs - Infections tropicales et méditerranéennes Vecteurs - Infections tropicales et méditerranéennes Dai Hoc Da Nang - University of Danang [Vietnam] Vecteurs - Infections tropicales et méditerranéennes Microbes Evolution Phylogénie et Infections Institut Hospitalier Universitaire Méditerranée Infection Microbes Evolution Phylogénie et Infections Institut Hospitalier Universitaire Méditerranée Infection Vecteurs - Infections tropicales et méditerranéennes Vecteurs - Infections tropicales et méditerranéennes Microbes Evolution Phylogénie et Infections Institut Hospitalier Universitaire Méditerranée Infection Microbes Evolution Phylogénie et Infections Institut Hospitalier Universitaire Méditerranée Infection Vecteurs - Infections tropicales et méditerranéennes Institut Hospitalier Universitaire Méditerranée Infection Centre méditerranéen de médecine moléculaire Hôpital l'Archet Microbes Evolution Phylogénie et Infections Institut Hospitalier Universitaire Méditerranée Infection Vecteurs - Infections tropicales et méditerranéennes Institut Hospitalier Universitaire Méditerranée Infection
• Publié dans Travel Medicine and Infectious Disease le 25/10/2020

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 01/07/2023
• Auteurs : Richard Sousa da SilvaEva BreuerSadhana ShankarShoji KawakatsuWacław HołówkoJoão Santos CoelhoHeithem JeddouTeiichi SugiuraMohammed GhallabDoris da SilvaGenki WatanabeFlorin BoteaNozomu SakaiPietro AddeoStylianos TzedakisFabian BartschKaja BalcerChetana LimFabien WereyVictor LópezLuciana Peralta MonteroRodrigo Sanchez ClariaJennifer LeitingNeeta VachharajaniEve HoppingOrlando TorresSatoshi HiranoDaan AndelJeroen HagendoornAlicja PsicaMatteo RavaioliKeun AhnTim ReeseLeonardo Agustin MontesGanesh GunasekaranCándido AlcázarJin LimMuhammad HaroonQian LuAntonio CastaldiTatsuya OrimoBeat MoeckliTeresa AbadíaLuis RuffoloJosefina Dib HasanFrancesca RattiEmmanuele KaufmannRoeland de WildeWojciech PolakUgo BoggiLuca AldrighettiLucas MccormackRoberto Hernandez-AlejandroAlejandro SerrabloChristian TosoAkinobu TaketomiJean GugenheimJiahong DongFaisal HanifJoon ParkJosé RamiaMyron SchwartzDiego RamischMichelle de OliveiraKarl OldhaferKoo KangMatteo CesconPeter LodgeInne RinkesTakehiro NojiJohn-Edwin ThomsonSu GohWilliam ChapmanSean ClearyJuan PekoljJean-Marc RégimbeauOlivier ScattonStéphanie TruantHauke LangDavid FuksPhilippe BachellierMasayuki OtsukaIrinel PopescuKiyoshi HasegawaMickael LesurtelRené AdamDaniel CherquiKatsuhiko UesakaKarim BoudjemaHugo Pinto MarquesMicha GrątHenrik PetrowskyTomoki EbataAndreas PrachaliasRicardo Robles-CamposPierre-Alain Clavien
• Organismes : Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Hospices Civils de Lyon
• Publié dans Annals of Surgery le 26/10/2020

---

Résumé : Objective: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities. Background: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures. Methods: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a five-year period (2016–2020). Benchmark cases were low-risk non-cirrhotic patients without significant co-morbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient. Results: Of 8044 patients, 2908 (36%) qualified as benchmark (low risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1,4-8 or H4-8) disclosed higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow up for a conclusive outcome evaluation following open anatomic major resection must be 3 months. Conclusion: These new benchmark cut-offs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation or novel chemotherapy regimens.

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 01/07/2023
• Auteurs : Julia MafféïsGuillaume Anthony OdriJacques-Marie MercierJustine LoinJean-Philippe PerrinAline JolyClaudia LetelierPierre CorreHélios Bertin
• Organismes : Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Hôpital Lariboisière-Fernand-Widal [APHP] Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Régional Universitaire de Tours Universidad de Chile = University of Chile [Santiago] Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Regenerative Medicine and Skeleton Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers
• Publié dans Journal of Cranio-Maxillofacial Surgery le 01/11/2020

---

Résumé : The aim of this study was to evaluate the sagittal and vertical relapses after Le Fort 1 osteotomy in bilateral cleft lip and palate (BCLP) patients. Lateral cephalograms before surgery, immediately after the procedure, at one year, and at least two years (when available) after surgery were superimposed. The positions of five landmarks were studied in a coordinate system. Uni- and multivariate analyses investigated the effect of various factors on the relapse. Of the 71 patients included for a BCLP, 54 presented complete data at one year, and 30 patients were included for the long follow-up study (mean of 55 months). The mean maxillary advancement was 6.2 mm on the sub-spinal point (A). Sagittal relapse occurred at one year (mean of 1.1 mm on point A, 0.7 mm on point prosthion (P); p < 0.0001) and progressed by 0.5 mm and 1.0 mm, respectively, on the same points at the last follow-up. The mean vertical relapse was 0.5 mm on point A (p = 0.044), 0.6 mm on point P (p = 0.16) and 0.5 mm on incisor (I) (p = 0.056). The vertical relapse was correlated to the degree of vertical movement. Three factors were associated to the recurrence including a prior pharyngeal flap, an associated mandibular osteotomy and smoking habits.

---

Fichiers liés : S1010518223001014.pdf

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 01/07/2023
• Auteurs : Bruce Stamblera John CammMarco AlingsPaul DorianHein HeidbuchelJaco HoutgraafPeter KoweyJose MerinoBlandine MondésertJonathan PicciniSean PokorneyPhilip SagerAtul VermaJ Marcus WhartonDavid BharuchaFrancis PlatSilvia ShardonofskyMichael ChenJames IpJames IpAlonzo JonesBruce StamblerDavid SchleinkoferStephen WintersWilson LamRobert GoldsteinIsaac Dor DorSandeep TalwarPadraig O'NeillMichael KorenSean BeinartSrivani AmbatiSean MazerRobert KinnKarine RoyRamin ManshadiRichard KukAditya VermaTimothy PhelanAlexandru StoianKenneth EllenbogenJ Vijay JayachandranTerence ConnellyMarcos DaccarettGaurang GandhiSuneet MittalAmir Abdel-WahabRalph AugostiniJohn IpDenise SorrentinoJean-Francois RouxRamandeep BrarClarence KhooMatthew BennettEric LoBenoit CoutuLaurence SternsGerald GreerPradeep GujjaRobert GianfagnaVijendra SwarupFelix SogadeStephen WiltonChristopher RuisiSaverio BarberaJavier BanchsVictoria KorleyChristopher SchulzeRoger DamleJeffrey Sean Healeya Shekhar PandeyJeffrey AndersonK VenkatachalamPeter NoseworthyBlandine MondésertAtul VermaDouglas FriarsThomas KamburEvan LockwoodGlenn MeiningerGreg OlsovskyAlonzo Jones SrGerald GreerRohit MehtaSaleem AkbarMalik SalmanBhola RamaRamesh AroraDhirenkumar ShahRakesh ShahMichael CammarataAndrew OwensKatherine LudingtonMarcus WhartonMichael BagheriMohammed KhanKenneth Warren CarrSultan SiddiqueSunthosh ParvathaneniSubodh DevabhaktuniAssad MouhaffelGeorge MarkLuigi Di BiaseSunil RangappaJared MortonHirad YarmohammadiAmin KarimAldo Martinez FleitesThomas NeroQaiser ShafiqBenoit CoutuShekhar PandeyYaariv KhaykinJacqueline JozaGilbert GosselinAllen SkanesJohn VyselaarDaniel SavardHein HeidbuchelOlivier XhaetEmmanuel CatezJohan VijgenPascal GodartRuben CasadoGeorges MairesseTom RossenbackerPeter HaemersEtienne HofferPierre HausmanAndras VertesGabor DurayErzsebet SzolnokiZoltan CsanadiFerenc LakatosMarco AlingsReinhart DormanY TuiningaW JansenSebastiaan VelthuisB van BemmelGerhard Jan Willem BechRon PistersSuzanne ValkTjeerd RomerJustin LuermansDriek BeelenMartijn van EckJaco HoutgraafThijs VetDirk ShellingsT OosterhofPawel MiekusWaldemar BebenekAgata Bielecka-DabrowaJacek GniotWitold ZmudaMichal KasprzakWojciech BalakPawel PtaszynskiJacek NowakJanusz ProkopczukAndrzej PrzybylskiIwona Wozniak-SkowerskaPawel DerejkoDanuta CzarneckaAdam JanasJose Luis Merino LlorensLuis TercedorAndres Iniguez RomoRicardo Ruiz GranellJose Ramon Gonzalez JuanateyDomingo Pascual-FigalManuel Martinez-SellesIgnacio Anguera CamosAlicia Ibanez CriadoJavier Matrinez BasterraAlvaro IzquierdoNuria Rivas GandaraJosep Alegret ColomeDiego Perez DiezMiguel Ángel Martínez HervásMaria MedinaJose María Segura Saint-GeronsAlonso Pedrote LealIgnacio Fernandez LozanoAurelio QuesadaJose Guerra RamosAxel SarriasJavier Ramos MaquedaJacques MansouratiPascal DefayeLaurence Guedon-MoreauAntoine MilhemMaxime de GuillebonPhilippe ChevalierMarc BadozCharalampos KriatselisGregor SimonisThorsten LewalterMarkus ZarseAndreas WilkeFabian KraemerAyham Al-Zoebi
• Organismes : Hôpital de la Cavale Blanche - CHRU Brest Optimisation des régulations physiologiques
• Publié dans The Lancet le 02/11/2020

---

Résumé : Background: Etripamil is a fast-acting, intranasally administered calcium-channel blocker in development for on-demand therapy outside a health-care setting for paroxysmal supraventricular tachycardia. We aimed to evaluate the efficacy and safety of etripamil 70 mg nasal spray using a symptom-prompted, repeat-dose regimen for acute conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm within 30 min. Methods: RAPID was a multicentre, randomised, placebo-controlled, event-driven trial, conducted at 160 sites in North America and Europe as part 2 of the NODE-301 study. Eligible patients were aged at least 18 years and had a history of paroxysmal supraventricular tachycardia with sustained, symptomatic episodes (≥20 min) as documented by electrocardiogram. Patients were administered two test doses of intranasal etripamil (each 70 mg, 10 min apart) during sinus rhythm; those who tolerated the test doses were randomly assigned (1:1) using an interactive response technology system to receive either etripamil or placebo. Prompted by symptoms of paroxysmal supraventricular tachycardia, patients self-administered a first dose of intranasal 70 mg etripamil or placebo and, if symptoms persisted beyond 10 min, a repeat dose. Continuously recorded electrocardiographic data were adjudicated, by individuals masked to patient assignment, for the primary endpoint of time to conversion of paroxysmal supraventricular tachycardia to sinus rhythm for at least 30 s within 30 min after the first dose, which was measured in all patients who administered blinded study drug for a confirmed atrioventricular-nodal-dependent event. Safety outcomes were assessed in all patients who self-administered blinded study drug for an episode of perceived paroxysmal supraventricular tachycardia. This trial is registered at ClinicalTrials.gov, NCT03464019, and is complete. Findings: Between Oct 13, 2020, and July 20, 2022, among 692 patients randomly assigned, 184 (99 from the etripamil group and 85 from the placebo group) self-administered study drug for atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia, with diagnosis and timing confirmed. Kaplan-Meier estimates of conversion rates by 30 min were 64% (63/99) with etripamil and 31% (26/85) with placebo (hazard ratio 2·62; 95% CI 1·66–4·15; p<0·0001). Median time to conversion was 17·2 min (95% CI 13·4–26·5) with the etripamil regimen versus 53·5 min (38·7–87·3) with placebo. Prespecified sensitivity analyses of the primary assessment were conducted to test robustness, yielding supporting results. Treatment-emergent adverse events occurred in 68 (50%) of 99 patients treated with etripamil and 12 (11%) of 85 patients in the placebo group, most of which were located at the administration site and were mild or moderate, and all of which were transient and resolved without intervention. Adverse events occurring in at least 5% of patients treated with etripamil were nasal discomfort (23%), nasal congestion (13%), and rhinorrhea (9%). No serious etripamil-related adverse events or deaths were reported. Interpretation: Using a symptom-prompted, self-administered, initial and optional-repeat-dosing regimen, intranasal etripamil was well tolerated, safe, and superior to placebo for the rapid conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm. This approach could empower patients to treat paroxysmal supraventricular tachycardia themselves outside of a health-care setting, and has the potential to reduce the need for additional medical interventions, such as intravenous medications given in an acute-care setting.

---

Source