Search

Your search keyword '"Sergii Moskovko"' showing total 9 results
Start Over Author "Sergii Moskovko"
9 results on '"Sergii Moskovko"'

1. Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis: a phase 2b, randomised, double-blind, placebo-controlled trial

Author

Daniel S Reich, Douglas L Arnold, Patrick Vermersch, Amit Bar-Or, Robert J Fox, Andre Matta, Timothy Turner, Erik Wallström, Xinyan Zhang, Miroslav Mareš, Farit A Khabirov, Anthony Traboulsee, Francois Grand'Maison, Francois Jacques, Michaela Tyblova, Eva Meluzinova, Radek Ampapa, Martin Valis, Pavel Hradilke, Pavel Stourac, Katrin Gross-Paju, David Laplaud, Guillaume Mathey, Bernard Uitdehaag, Evgeny Evdoshenkoo, Ekaterina Popova, Maria Zakharova, Natalia Totolyan, Igor Litvinenko, Farit Khabirov, Stella Sivertseva, Viera Hancinova, Ema Kantorova, Maria Luisa Martinez Gines, Xavier Montalban, Sara Eichau Maduano, Jose Meca-Lallana, Lluís Ramió-Torrentà, Tetyanna Nehrych, Valeriy Pashkovskyy, Sergii Moskovko, Oleksandr Kalbus, Marta Khavunka, Volodymyr Pryshchepa, Alla Goloborodko, Daniel Wynn, William Honeycutt, Sibyl Wray, Brian Steingo, Christopher LaGanke, Deren Huang, John Michael Hemphill, Lawrence Goldstick, and Derrick Robertson

Subjects
Adult, Central Nervous System, Male, medicine.medical_specialty, Population, Placebo-controlled study, Placebo, law.invention, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Randomized controlled trial, Double-Blind Method, law, Recurrence, Internal medicine, Outcome Assessment, Health Care, Agammaglobulinaemia Tyrosine Kinase, Medicine, Humans, education, Protein Kinase Inhibitors, Inflammation, education.field_of_study, Cross-Over Studies, Dose-Response Relationship, Drug, business.industry, Multiple sclerosis, Middle Aged, medicine.disease, Crossover study, Magnetic Resonance Imaging, Clinical trial, Cohort, Female, Neurology (clinical), business
Abstract

Summary Background Tolebrutinib is an oral, CNS-penetrant, irreversible inhibitor of Bruton’s tyrosine kinase, an enzyme expressed in B lymphocytes and myeloid cells including microglia, which are major drivers of inflammation in multiple sclerosis. We aimed to determine the dose-response relationship between tolebrutinib and the reduction in new active brain MRI lesions in patients with relapsing multiple sclerosis. Methods We did a 16-week, phase 2b, randomised, double-blind, placebo-controlled, crossover, dose-finding trial at 40 centres (academic sites, specialty clinics, and general neurology centres) in ten countries in Europe and North America. Eligible participants were adults aged 18–55 years with diagnosed relapsing multiple sclerosis (either relapsing-remitting or relapsing secondary progressive multiple sclerosis), and one or more of the following criteria: at least one relapse within the previous year, at least two relapses within the previous 2 years, or at least one active gadolinium-enhancing brain lesion in the 6 months before screening. Exclusion criteria included a diagnosis of primary progressive multiple sclerosis or a diagnosis of secondary progressive multiple sclerosis without relapse. We used a two-step randomisation process to randomly assign eligible participants (1:1) to two cohorts, then further randomly assign participants in each cohort (1:1:1:1) to four tolebrutinib dose groups (5, 15, 30, and 60 mg administered once daily as an oral tablet). Cohort 1 received tolebrutinib for 12 weeks, then matched placebo (ie, identical looking tablets) for 4 weeks; cohort 2 received 4 weeks of placebo followed by 12 weeks of tolebrutinib. Participants and investigators were masked for dose and tolebrutinib-placebo administration sequence; investigators, study team members, and study participants did not have access to unmasked data. MRI scans were done at screening and every 4 weeks over 16 weeks. The primary efficacy endpoint was the number of new gadolinium-enhancing lesions detected on the scan done after 12 weeks of tolebrutinib treatment (assessed at week 12 for cohort 1 and week 16 for cohort 2), relative to the scan done 4 weeks previously, and compared with the lesions accumulated during 4 weeks of placebo run-in period in cohort 2. Efficacy data were analysed in a modified intention-to-treat population, using a two-step multiple comparison procedure with modelling analysis. Safety was assessed for all participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT03889639), EudraCT (2018-003927-12), and WHO (U1111-1220-0572), and has been completed. Findings Between May 14, 2019, and Jan 2, 2020, we enrolled and randomly assigned 130 participants to tolebrutinib: 33 to 5 mg, 32 to 15 mg, 33 to 30 mg, and 32 to 60 mg. 129 (99%) completed the treatment regimen and 126 were included in the primary analysis. At treatment week 12, there was a dose-dependent reduction in the number of new gadolinium-enhancing lesions (mean [SD] lesions per patient: placebo, 1·03 [2·50]; 5 mg, 1·39 [3·20]; 15 mg, 0·77 [1·48]; 30 mg, 0·76 [3·31]; 60 mg, 0·13 [0·43]; p=0·03). One serious adverse event was reported (one patient in the 60 mg group was admitted to hospital because of a multiple sclerosis relapse). The most common non-serious adverse event during tolebrutinib treatment was headache (in one [3%] of 33 in the 5 mg group; three [9%] of 32 in the 15 mg group; one [3%] of 33 in the 30 mg group; and four [13%] of 32 in the 60 mg group). No safety-related discontinuations or treatment-related deaths occurred. Interpretation 12 weeks of tolebrutinib treatment led to a dose-dependent reduction in new gadolinium-enhancing lesions, the 60 mg dose being the most efficacious, and the drug was well tolerated. Reduction of acute inflammation, combined with the potential to modulate the immune response within the CNS, provides a scientific rationale to pursue phase 3 clinical trials of tolebrutinib in patients with relapsing and progressive forms of multiple sclerosis. Funding Sanofi.

Published
2021

2. Ticagrelor Added to Aspirin in Acute Nonsevere Ischemic Stroke or Transient Ischemic Attack of Atherosclerotic Origin

Author

Pierre Amarenco, Hans Denison, Scott R. Evans, Anders Himmelmann, Stefan James, Mikael Knutsson, Per Ladenvall, Carlos A. Molina, Yongjun Wang, S. Claiborne Johnston, Kenneth Butcher, Shuya Li, Huaguang Zheng, David Skoloudik, Lawrence Wong, Ketevana Meshkova, Nijasri C. Suwanwela, Sebastian Ameriso, Leonardo Gonzalez, Pablo Ioli, Lorena Jure, Guillermo Povedano, Guadalupe Bruera, Gustavo Herrera, Juan Jose Martin Artesi, Virginia A. Pujol Lereis, Conrado J. Estol, Maia Gomez Schneider, Santiago Pigretti, Fernando Lipovestky, María Cristina Zurru, Stephen Davis, Andrew Wong, Tissa Wijeratne, Arman Sabet, Andrew Lee, Vincent Thijs, Robin Lemmens, Laetitia Yperzeele, Geert Vanhooren, Peter Vanacker, Iris Vansteenkiste, Vicky Maqueda, André Peeters, Marie-Christine Hasenbroekx, Van Daele, Wendy Hasenbroekx, Adinda De Pauw, Regilio Oedit, Wouter De Vooght, Philippe Desfontaines, Yves Vandermeeren, Marianna D.A. Dracoulakis, Rodrigo Bazan, Octavio M. Pontes Neto, Daniel D.C. Bezerra, Luiz C. Marrone, Pedro A. Kowacs, Carla H.C. Moro, Paulo C.O. Macelino, Marco Tulio A. Pedatella, Ekaterina Titianova, Ivan Staikov, Dimitar Maslarov, Plamen Petkov, Tanya Beleva, Borislav Kralev, Nikolay Sotirov, Dimcho Hristov, Rumeliya M. Ivanova, Margarita V. Mihailova, Ashfaq M. Shuaib, Andrew Demchuk, Michel Beaudry, Anthony R. Winder, Sumiti Nayar, Xingquan Zhao, Guoqiang Wen, Xueshuang Dong, Guozhong Li, Zhaohui Zhang, Huisheng Chen, Dong Wang, Xiaohong Li, Yuncheng Wu, Xu Zhang, Baorong Zhang, Wenke Hong, Xiaogang Li, Lijuan Wang, Li Liu, Xiaolin Xu, Peifu Wang, Weihong Zheng, Jinsheng Zeng, Yukai Wang, Yan Jia, Yongqiu Li, Bo Hu, Wei Shen, Zhi Song, Zhiping Hu, Yunhai Liu, Kaifu Ke, Deqin Geng, Shigang Zhao, Runxiu Zhu, Qiumin Qu, Xiuli Zhao, Qi Wan, Yunhua Yue, Huishan Du, Meiyun Zhang, Yan Wang, Dongfang Li, Dongyu Wang, Yongqiang Li, Xufang Xie, Tingmin Yu, Qi Liu, Mingxiu Yang, Xiaoping Pan, Lijun Xu, Deen Xu, Gang Li, Anding Xu, Martin Roubec, Petr Geier, Daniel Vaclavik, Jiri Neumann, Jana Bednarova, Robert Mikulik, David Hlinovsky, Charlotte Cordonnier, Igor Sibon, Caroline Arquizan, Sonia Alamowitch, Bertrand Lapergue, Jean-Marc Olivot, Nicolas Raposo, Marie-Hélène Mahagne, Emmanuel Touze, Gilles Rodier, Stéphane Vannier, Yves Samson, Michael Obadia, Emmanuel Ellie, Benoît Guillon, Serge Timsit, Yannick Bejot, Valérie Wolff, Didier Smadja, Aude Bagan-Triquenot, Pierre Garnier, Xavier Ducrocq, Peggy Reiner, Thierry Moulin, Frédéric Philippeau, Fernando Pico, Sébastien Richard, Joachim Röther, Jörg Berrouschot, Hassan Soda, Carsten Pohlmann, Christoph Terborg, Darius G. Nabavi, Rainer Dziewas, Martin Köhrmann, Jörg Glahn, Lars Marquardt, Bernd Kallmünzer, Karin Weißenborn, Yannie Oi-Yan Soo, Richard Li, Wing Chi Fong, Siu Hung Li, Raymond Cheung, Kin Keung Yip, Joshua Wai Ming Fok, Michael Y.P. Fu, Norbert Szegedi, Krisztián Pozsegovits, Attila Valikovics, Gyula Pánczél, Csilla Rózsa, Péter Diószeghy, Attila Csányi, Levente Kerényi, Valéria Nagy, László Szapáry, Dániel Bereczki, Sándor Molnár, Gyula Timár, András G. Folyovich, Mária Sátori, Ildikó Vastagh, Praveen S. Kumar, Rajnish Kumar, Atul Prasad, Vikram Sharma, Alok Verma, Indraneel Basu, Abu Z. Ansari, Vijaya Pamidimukkala, Raghavendra B, null S, Vivek D. Junewar, Sumit Singh, Advait Prakash Kulkarni, Padma M.V. Srivastava, K. Pramod, Sanjay G. Ramteke, Jaideep Bansal, Kewal Krishan, Hrishikesh Kumar, Priyanka V. Kashyap, T.C.R. Ramakrishnan, Gopal R. Adrasetty, Amit Yeole, Rahul B. Baviskar, Giancarlo Agnelli, Danilo Toni, Stefano Ricci, Rossana Tassi, Giuseppe Micieli, Michelangelo Mancuso, Giovanni Orlandi, Alberto Chiti, Marialuisa Delodovici, Federico Carimati, Alessandro De Vito, Francesco Perini, Cinzia Finocchi, Tiziana Tassinari, Massimo Del Sette, Luisa Roveri, Andrea Zini, Guido Bigliardi, Francesca R. Pezzella, Letizia Cupini, Alessandro Adami, Giampaolo Tomelleri, Carla Zanferrari, Angel A. Arauz Góngora, Minerva López Ruíz, Angelica Ruíz Franco, José O.J. Chacon Romero, Fernando Cruz Castillo, Jose L. Ruiz-Sandoval, Jesús D. López Tapia, Edgar A. Castillo Vargas, Juan F. Gongora Rivera, Guillermo Rivera Martinez, Jorge Villarreal Careaga, Nilton Custodio, Oscar G. Pamo Reyna, Cesar A. Castañeda, Edwin J. Pretell, Nestor Najar, Julio C. Perez, Luisa Cardoza, Carlos Chavez, Maria Reyes, Anna Członkowska, Waldemar Fryze, Piotr Sobolewski, Ryszard Nowak, Dorota Szkopek, Zbigniew Bąk, Sławomir Brzozowski, Waldemar Brola, Marek Zalisz, Konrad Rejdak, Marta Bilik, Małgorzata Fudala, Andrzej Tutaj, Anetta Lasek-Bal, Jan Kochanowicz, Bartosz Karaszewski, Tomasz Berkowicz, Beata Zwiernik, Dorota Różański, Jan P. Mejnartowicz, Szymon Jurga, Jacek Rożniecki, Maciej Świat, Ovidiu A. Bajenaru, Cristina A. Panea, Mihaela A. Simu, Rodica Balasa, Dan I. Cuciureanu, Bogdan O. Popescu, Monica Sabau, Corina Roman-Filip, Liudmila Odnopozova, Oleg Artyukov, Anna Milto, Liudmila V. Stakhovskaya, Sergei Aksentiev, Svetlana E. Chuprina, Elena B. Kuznetsova, Ilya I. Sholomov, Alexander Malygin, Elena Mordvintseva, Rostislav Y. Nilk, Inna Ershova, Dina Khasanova, Leila Akhmadeeva, Aida Iakupova, Ekaterina A. Drozdova, Marine Tanashyan, Evgenij Pudov, Lybov A. Shpagina, Svetlana Berns, Liudmila G. Lenskaya, Konstantin Golikov, Andrey V. Kovalenko, Elena Vasilieva, Elena Reznik, Mikhail Zykov, Evgeniy Kovalchuk, Dmitry Popov, Andrey Belkin, Olga Androfagina, Tatyana Lokshtanova, Elena V. Melnikova, Fahmi Al-Senani, Nouf Almansour, Fawaz Alhussein, Ali Alkhathaami, Saeed Alghamdi, Miroslav Brozman, Marta Mikloskova, Georgi Krastev, Vlastimil Serdahely, Michal Kovacik, Ladislav Gurcik, Miloslav Dvorak, Egon Kurca, Andrea Cimprichova, Marian Kycina, Erika Zacharova, Richard Risnovsky, Hee-Joon Bae, Kyung Bok Lee, Yong-Jin Cho, Jong-Moo Park, Joon-Tae Kim, Jun Lee, Jae-Kwan Cha, Sung-Il Sohn, Dong-Ick Shin, Soo Joo Lee, Byung-Chul Lee, Jay Chol Choi, Moo Seok Park, Dae-Il Chang, Joung-Ho Rha, Sang Min Sung, Yangha Hwang, Jaume Roquer González, Jaime Masjuan Vallejo, Meritxell Gomis Cortina, Francisco Moniche Álvarez, Miguel Ángel Gamero García, Soledad Pérez Sánchez, Francisco Purroy García, Santiago Trillo Senín, Tomás Segura Martín, Joaquín Serena Leal, Juan Arenillas Lara, Joan Martí-Fàbregas, Aida Lago Martín, Carlos Tejero Juste, Javier Marta Moreno, Nicolás López Hernández, Lars Sjöblom, Ann Charlotte Laska, Margarita Callander, Thomas Mooe, Jan-Erik Karlsson, Mihaela Oana Romanitan, Arne Lindgren, Niaz Ahmed, Björn Cederin, Christine Kremer, Tsong-Hai Lee, Jiann-Shing Jeng, Chih-Hung Chen, Helen L. Po, Chia-Wei Liou, Huey-Juan Lin, Ruey-Tay Lin, Hsiu-Fen Lin, Li-Ming Lien, Lung Chan, Wei-Shih Huang, Wen-Yi Huang, Ta-Cheng Chen, Chin-I Chen, Po-Lin Chen, Chun-Pai Yang, Yu Sun, Aurauma Chutinet, Tasanee Tantirittisak, Sombat Muengtaweepongsa, Yongchai Nilanont, Somsak Tiamkao, Chesda Udommongkol, Witoon Jantararotai, Tabtim Chongsuvivatwong, Suwat Srisuwananukorn, Wasutha Khaykhaew, Supachai Paiboonpol, Makorn Limudomporn, Saengduan Mayotarn, Kanoksri Samintharapanya, Arkhom Arayawichanon, Thanoot Thamangraksat, Duangpol Srimanee, Galyna Chmyr, Nataliya Tomakh, Alla Cherkez, Sergii Moskovko, Vadym Nikonov, Svitlana Shkrobot, Lyudmyla Shulga, Hanna Hrebeniuk, Valentyna Yavorska, Nataliia Lytvynenko, Marta Khavunka, Iryna Kobets, Nataliia Chemer, Ivanna Tashchuk, Olha Myronova, Thang H. Nguyen, Tan V. Vo, Thanh T. Tran, Nga T.P. Nguyen, Anh D. Nguyen, Binh T. Nguyen, Thang B. Nguyen, Ngoc H. Nguyen, Quang D. Nguyen, Nhan D. Le, Dai D. Pham., UCL - SSS/IONS - Institute of NeuroScience, UCL - (MGD) Service de neurologie, Yperzeele, Laetitia, and THALES Steering Committee and Investigators

Subjects
Male, Atherosclerotic stenosis, Ticagrelor, Neurology, Neurologi, Original Contributions, population, Constriction, Pathologic, Severity of Illness Index, Recurrence, Secondary Prevention, Medicine, Cardiac and Cardiovascular Systems, Stroke, education.field_of_study, Aspirin, Kardiologi, Dual Anti-Platelet Therapy, Ischemic strokes, Middle Aged, stroke, Ischemic Attack, Transient, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Cardiology, ÍNDICE DE GRAVIDADE DA DOENÇA, Female, Cardiology and Cardiovascular Medicine, medicine.drug, medicine.medical_specialty, aspirin, Population, atherosclerosis, death, ticagrelor, transient ischemic attack, Clinical and Population Sciences, Internal medicine, Humans, education, Aged, Ischemic Stroke, Proportional Hazards Models, Advanced and Specialized Nursing, business.industry, Atherosclerosis, medicine.disease, Cerebrovascular Disorders, Ischemic stroke, Human medicine, Neurology (clinical), business, Platelet Aggregation Inhibitors
Abstract

Supplemental Digital Content is available in the text., Background and Purpose: Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events. Methods: In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–30) or placebo added to aspirin (300–325 mg on day 1 followed by 75–100 mg daily for days 2–30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days. Results: Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56–0.96], P=0.023) resulting in a number needed to treat of 34 (95% CI, 19–171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74–1.08]; P=0.23, Pinteraction=0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively (P=NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04–16.9], P=0.001). Conclusions: In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19–171). Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03354429.

Published
2020

3. Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes)

Author

J. Donald Easton, Maria Aunes, Gregory W. Albers, Pierre Amarenco, Sara Bokelund-Singh, Hans Denison, Scott R. Evans, Peter Held, Marianne Jahreskog, Jenny Jonasson, Kazuo Minematsu, Carlos A. Molina, Yongjun Wang, K.S. Lawrence Wong, S. Claiborne Johnston, Sebastiá F. Ameriso, Geoffrey Donnan, Robin Lemmens, Ayrton Massaro, Ekaterina Titianova, Michael D. Hill, Pablo Lavados, David Skoloudik, Joachim Röther, Szegedi Norbert, Giancarlo Agnelli, Natan Bornstein, Norio Tanahashi, Angel Arauz Góngora, Edwin Pretell, Maria Cristina Z. San Jose, Anna Czlonkowska, Ovidiu Bajenaru, Ludmila Stakhovskaya, Miroslav Brozman, Jong-Sung Kim, Nils Wahlgren, Patrik Michel, Tsong Hai Lee, Nijasri Charnnarong Suwanwela, Kursad Kutluk, Sergii Moskovko, Scott Kasner, Daniel Laskowitz, Wayne Clark, Huy Thang Nguyen, Sebastian Ameriso, Sandra Lepera, Marina Romano, David Paulon, Pablo Ioli, Cristina Zurru, Guadalupe Bruera, Lorena Jure, Francisco Klein, Guillermo Povedano, Christopher Levi, Thanh Phan, Romesh Markus, Craig Anderson, Arman Sabet, Stephen Davis, Andrew Lee, Timothy Kleinig, Andrew Wong, Martin Krause, Jim Jannes, Tissa Wijeratne, Dimitri Hemelsoet, André Peeters, Philippe Tack, Peter Vanacker, Patrice Laloux, William Van Landegem, Geert Vanhooren, Philippe Desfontaines, Marc Van Orshoven, Fabio Oliveira, Mauricio Friedrich, Rosane Brondani, Rubens Gagliardi, Soraia Fabio, Marianna Dracoulakis, Rodrigo Bazan, Luiz Marrone, Octavio Pontes Neto, Gisele Silva, Pedro Kowacs, Paraskeva Stamenova, Marin Daskalov, Ivan Staikov, Dimo Baldaranov, Dimitar Maslarov, Hristo Lilovski, Plamen Petkov, Neli Petrova, Radoslav Mavrov, Veska Markova, Valeria Petrova, Tanya Beleva, Borislav Kralev, Nikolay Sotirov, Veska Lekova, Dimcho Hristov, Vera Ermenkova, Lyudmil Mateev, Rumeliya Mitkova, Liybomir Haralanov, Rosen Ikonomov, Margarita Mihailova, Ivan Georgiev, Ashfaq Shuaib, Vladimir Hachinski, Jean-Martin Boulanger, Sharan Mann, Ayman Hassan, Ariane Mackey, Bijoy Menon, Jeffrey Minuk, Muzaffar Siddiqui, Marsha Eustace, Lucia Vieira, Daniel Selchen, Michel Beaudry, Grant Stotts, Angel Castro, Kristo Gasic, Rodrigo Rivas, Pablo Sanchez, Andres Roldan, Ingrid Grossmann, Christian Figueroa, Jimei Li, Xiaolin Xu, Huisheng Chen, Xiaohong Li, Yi Yang, Chunsheng Zhang, Baojun Wang, Guanglai Li, Dong Wang, Hong Lin, Yamei Tang, Anding Xu, Yanjiang Wang, Wenke Hong, Zhi Song, Xu Zhang, Xiaoping Jin, Yun Xu, Fuling Yan, Weihong Zheng, Xiaoping Wang, Qiang Dong, Zhongxin Zhao, Baorong Zhang, Wangtao Zhong, Guoqiang Wen, Jun Xu, Guozhong Li, Xueshuang Dong, Xiangyang Tian, Zhaohui Zhang, En Xu, Kaixiang Liu, Jun Chen, Ondrej Skoda, Edvard Ehler, Daniel Vaclavik, Daniel Sanak, Sylva Klimosova, Eva Vitkova, Jan Fiksa, Robert Mikulik, Jiri Neumann, Richard Plny, Didier Leys, Igor Sibon, Jean-Louis Mas, Sonia Alamowitch, Fernando Pico, Hassan Hosseini, Marie-Hélène Mahagne, Emmanuel Touze, Wilfried Vadot, Stéphane Vannier, Norbert Nighoghossian, Yves Samson, Pierre Garnier, Emmanuel Ellie, Benoît Guillon, Serge Timsit, Maurice Giroud, Frédéric Philippeau, Aude Bagan-Triquenot, Valérie Wolff, Nicolas Raposo, Michel Obadia, Severine Debiais, Jérôme Grimaud, Stéphane Illouz, Didier Smadja, Cédric Urbanczyk, Jörg Berrouschot, Christian Weimar, Georg Gahn, Hassan Soda, Sven Klimpe, Darius Nabavi, Jörg Glahn, Martin Köhrmann, Lars Krause, Christoph Terborg, Peter Urban, Thorsten Steiner, Andreas Ferbert, Rainer Dziewas, Günter Seidel, Götz Thomalla, Richard Li, Wing Chi Fong, Raymond Cheung, Norbert Szegedi, Krisztián Pozsegovits, Attila Valikovics, Gyula Pánczél, Csilla Rózsa, László Németh, Péter Diószeghy, Csaba Óváry, Attila Csányi, Levente Kerényi, Valéria Nagy, Sámuel Komoly, Dániel Bereczki, Sándor Molnár, István Kondákor, David Tanne, Guy Raphaeli, Gregory Telman, Ronen Leker, Yair Lampl, Francesco Corea, Stefano Ricci, Donata Guidetti, Giovanni Malferrari, Simona Marcheselli, Giuseppe Micieli, Andrea Zini, Vincenzo Di Lazzaro, Carlo Gandolfo, Andrea Salmaggi, Rossana Tassi, Maurizia Rasura, Giovanni Orlandi, Giancarlo Comi, Michelangelo Mancuso, Marialuisa Delodovici, Paolo Bovi, Domenico Consoli, Kimiaki Utsugisawa, Tsuneo Fujita, Hideyuki Kurihara, Chikashi Maruki, Takeshi Hayashi, Tsuneaki Ogiichi, Morio Kumagai, Katsunobu Takenaka, Kazunori Toyoda, Kazuhiro Takamatsu, Ryo Ogami, Shigenari Kin, Takeshi Aoki, Katsumi Takizawa, Shigehiro Omori, Takehiko Umezawa, Yasuyuki Toba, Yutaka Nonoyama, Hidemitsu Nakagawa, Takashi Naka, Masanori Morimoto, Shuichi Matsumoto, Tsutomu Hitotsumatsu, Tatsuya Shingaki, Satoshi Okuda, Mamoru Ota, Nobuyuki Sakai, Takeshi Yamada, Jun Niwa, Hitoshi Fujita, Akihito Moriki, Kimihiro Yoshino, Yoshihisa Fukushima, Takahisa Mori, Atsushi Sato, Yoshikazu Kusano, Michiya Kubo, Masashi Yamazaki, Takao Ooasa, Takafumi Nishizaki, Naoki Kitagawa, Masahiro Yasaka, Yasuhiro Manabe, Akira Yoshioka, Masayuki Ishihara, Takato Kagawa, Toshikazu Ichihashi, Hideki Matsuoka, Yasuhiro Ito, Masahiro Yamasaki, Hitonori Takaba, Hisatoshi Saito, Masahiro Sato, Kazumasa Fukuda, Sumio Endo, Minoru Kidooka, Toshitaka Umemura, Yuriko Kikkawa, Shuta Toru, Kentaro Yamada, Hideki Sakai, Jun Asari, Masayuki Ezura, Hisashi Nitta, Keiko Nagano, Jun Ochiai, Keiichi Sakai, Yasutaka Kobayashi, Yasuhiro Yoshii, Hirotomo Miake, Tomohiro Takita, Hidekazu Taniguchi, Kazuhiko Kuroki, Takamitsu Mizota, Kenichi Yamamoto, Hiroshi Nakane, Takeshi Iwanaga, Kei Chiba, Tetsuyuki Yoshimoto, Tsuyoshi Torii, Takeo Kitagawa, Hiroshi Takashima, Naoki Shirasaki, Makoto Dehara, Naomichi Wada, Kensuke Hamada, Noriyuki Kato, Yoshinori Go, Ichiro Izumi, Hirotomo Ninomiya, Junichiro Kumai, Yoshikazu Nakajima, Yasuhiko Kaku, Yukihiro Isayama, Masahiro Kawanishi, Shinya Noda, Kazuhide Yamamoto, Takanori Hazama, Hiroshi Takahashi, Yohei Tanaka, Takashi Hata, Kiyoshi Kazekawa, Eisuke Furui, Hideki Hondo, Nobuyuki Sato, Katsusuke Kusunoki, Kazunori Nanri, Satoshi Abe, Noboru Sasaoka, Takayuki Kuroyanagi, Hisahiko Suzuki, Kouzou Fukuyama, Kimihiro Nakahara, Fernando Gongora, Carlos Cantú Brito, Jorge Villarreal Careaga, Rosalia Vazquez Alfaro, Geronimo Aguayo Leytte, Percy Berrospi, Carlos Chavez, Liliana Rodriguez, Nilton Custodio, Cesar Castañeda, Julio Perez, Maria Cristina San Jose, Alejandro Baroque, Epifania Collantes, Abdias Aquino, Alejandro Díaz, Artemio Roxas, Johnny Lokin, Joel Advincula, Emerito Calderon, Jose Navarro, John Hiyadan, Arturo Surdilla, Danuta Ryglewicz, Grzegorz Krychowiak, Waldemar Fryze, Piotr Sobolewski, Ryszard Nowak, Urszula Fiszer, Beata Papierowska, Justyna Zielińska-Turek, Anetta Lasek-Bal, Ewa Kołodziejska, Anna Kamińska, Bożena Adamkiewicz, Andrzej Tutaj, Dorota Szkopek, Krzysztof Musiatowicz, Zbigniew Bąk, Sławomir Brzozowski, Waldemar Brola, Antoni Ferens, Marek Zalisz, Konrad Rejdak, Monika Rudzińska, Cristina Panea, Mihaela Simu, Rodica Balasa, Iulian Cuciureanu, Bogdan Popescu, Monica Sabau, Corina Roman-Filip, Leonid Pimenov, Alla Gekht, Anna Milto, Ivan Shchukin, Vladimir Parfenov, Liudmila Stakhovskaya, Mikhail Arkhipov, Nadezhda Sokolova, Enver Bogdanov, Radiy Esin, Dina Khasanova, Konstantin Golikov, Elena Melnikova, Leonid Zaslavskiy, Igor Voznyuk, Alexander Nazarov, Leila Akhmadeeva, Aida Iakupova, Nikolay Shamalov, Galina Belskaya, Svetlana Chuprina, Olga Denisova, Ekaterina Drozdova, Yuliya Karakulova, Ilya Sholomov, Nikolay Spirin, Elena Vostrikova, Elena Mordvintseva, Vera Grigoryeva, Dmitry Zateyshchikov, Vladimir Gorbachev, Zhanna Chefranova, Mikhail Dudarev, Rostislav Nilk, Alexey Rozhdestvenskiy, Ladislav Gurcik, Miloslav Dvorak, Georgi Krastev, Egon Kurca, Juraj Vyletelka, Jong Sung Kim, Hee-Joon Bae, Yong-Won Kim, Joon-Tae Kim, Jae-Kwan Cha, Hyo Suk Nam, Dae-Il Chang, Yong-Seok Lee, Kyungmi Oh, Sung-Wook Yu, Sung-Il Sohn, Jun Lee, Han Jin Cho, Eung-Gyu Kim, Joung-Ho Rha, Seo Hyun Kim, Carlos Molina Cateriano, Joaquín Serena Leal, José Vivancos Mora, Manuel Rodríguez Yañez, Jaume Roquer González, Francisco Purroy García, Meritxell Gomis Cortina, Jaime Masjuan Vallejo, Juan Arenillas Lara, Tomás Segura Martín, José Antonio Egido Herrero, Jose Ignacio Tembl Ferrairó, Jaime Gállego Culleré, Francisco Moniche Álvarez, Anna Steinberg, Margarita Callander, Ann Charlotte Laska, Lena Bokemark, Thomas Mooe, Tor-Björn Käll, Lennart Welin, Lars Sjöblom, Joakim Hambraeus, Jörg Teichert, Hans Wannberg, Johan Sanner, Bo Ramströmer, Bo Ziedén, Stefan Olsson Hau, Claes Gustafsson, Timo Kahles, Philippe Lyrer, Marcel Arnold, Martin Liesch, Friedrich Medlin, Carlo Cereda, Georg Kägi, Andreas Luft, Emmanuel Carrera, Tsong-Hai Lee, Helen L. Po, Chang-Ming Chern, Li-Ming Lien, Lung Chan, Chung-Hsiang Liu, Shey-Lin Wu, Jiann-Der Lee, Chih-Hung Chen, Huey-Juan Lin, Ruey-Tay Lin, Wei-Hsi Chen, Yu Sun, Tasanee Tantirittisak, Sombat Muengtaweepongsa, Yongchai Nilanont, Somsak Tiamkao, Chesda Udommongkol, Kanokwan Watcharasaksilp, Witoon Jantararotai, Hadiye Sirin, Birsen Ince, Talip Asil, Murat Arsava, Tulay Kurt Incesu, Hulya Tireli, Hayriye Kucukoglu, Fikri Ak, Ali Unal, Serefnur Ozturk, Nevzat Uzuner, Galyna Chmyr, Volodymyr Lebedynets, Vadym Nikonov, Lyudmyla Shulga, Volodymyr Smolanka, Marta Khavunka, Valentyna Yavorska, Nataliya Tomakh, Olexandr Kozyolkin, Galyna Litovaltseva, Maarten Lansberg, Richard Bernstein, David Brown, Jonathan Dissin, Carmelo Graffagnino, Jonathan Harris, William Hicks, Irene Katzan, Jeffrey Kramer, Joshua Willey, Scott Silliman, Sidney Starkman, David Thaler, Margaret Tremwel, Mauricio Concha, Kumar Rajamani, Bhuvaneswari Dandapani, Brian Silver, Nathan Deal, Ira Chang, Ameer Hassan, Steven Rudolph, Kenneth Fischer, Howard Kirshner, William Logan, Sidney Mallenbaum, Hebah Hefzy, Julius Latorre, Steven Levine, Anthony Ciabarra, Rima Dafer, Benjamin Anyanwu, Laurel Cherian, Spozhmy Panezai, Anna Khanna, Jodi Dodds, Michel Torbey, James Gebel, Henry Woo, David Chiu, Xiao Androulakis, William Burgin, Maria Pineda, Engin Yilmaz, Irfan Altafullah, Christine Boutwell, Salvador Cruz-Flores, Biggya Sapkota, Pierre Fayad, Michael Jacoby, Shahid Rafiq, Efrain Salgado, Eugene Lafranchise, Warren Felton, Ramesh Madhavan, Osama Zaidat, Connie Pieper, Ralph Riviello, Aaron Burnett, Michelle Fischer, Nina Gentile, Christopher Calder, Dennis Dietrich, Jonathan Cross, Larry Blankenship, Liliana Montoya, Wendell Grogan, Mark Young, Farrukh Khan, Duane Campbell, Nizar Daboul, Andrey Espinoza, Paul Cullis, Gilberto Concepcion, John Wulff, Haider Afzal, Naseem Jaffrani, William Reiter, Tamjeed Arshad, Timothy Lukovits, James Welker, Fen Lei Chang, Aamir Badruddin, Viken Babikian, Ravi Menon, James Sander, Mellanie Springer, Ashish Nanda, Luis Mas, Raj Rajan, Bruce Silverman, David Huang, David Carpenter, Joni Clark, Marilou Ching, Sunitha Santhakumar, Jeffrey Gould, Vibhav Bansal, Gabriel Vidal, Timothy Mikesell, John Brick, William French, Qaisar Shah, Christine Holmstedt, Nadir Ishag-Osman, John Kostis, Abbas Shehadeh, Pramodkumak Sethi, Asher Imam, Carl Mccomas, Duc Tran, Mehari Gebreyohanns, Brian Wiseman, Maheen Malik, Aron Schwarcz, Dorothea Altschul, John Castaldo, Amer Alshekhlee, Stephen Gancher, Nagesh Krish, Mai Nguyen-Huynh, Margaret Tremwell, Jitendra Sharma, Lance Lee, William Neil, Fazeel Siddiqui, Ali Malek, Charles Romero, Thang Nguyen Huy, Hoa Hoang, Thang Nguyen, Anh Nguyen, Hung Nguyen, Laboratoire de Recherche Vasculaire Translationnelle ( LVTS ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), AstraZeneca, National Cerebral and Cardiovascular Center ( NCCC - OSAKA ), Osaka University [Osaka], Department of Neurology ( Dep Neuro - BEIJING ), Tiantan Hospital, University of Melbourne, Faculty of Mathematics and Statistics, Ton Duc Thang University, Ho Chi Minh City, Heidelberg University, Centre hospitalier de Namur, IBM Thomas J. Watson Research Center, IBM, Bulgarian Academy of Sciences, Department of Clinical Neurological Sciences [London, Canada], University of Western Ontario ( UWO ), Servicio de Neurologia ( SANTIAGO - Neurologie ), Universidad de Santiago de Chile [Santiago] ( USACH ) -Universidad del Desarrollo, Institut de Chimie de Clermont-Ferrand - Clermont Auvergne ( ICCF ), Sigma CLERMONT ( Sigma CLERMONT ) -Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Universidad de Talca, Shanghai Second Polytechnic University, Northwest Normal University [Lanzhou], Zhongda Hospital, Southeast University [Jiangsu], Cryogenics Laboratory ( CRYOGENICS LABORATORY ), Huazhong University of Science and Technology [Wuhan] ( HUST ) -Wuhan University [China], Centre for Synthetic and Systems Biology, University of Edinburgh-School of Biological Sciences, Duke university [Durham], Fiber Glass, Glass Business and Discovery Center, PPG Industries, National University of Defense Technology [Changsha], School of Oceanography [Seattle], University of Washington [Seattle], Key Laboratory of New Processing Technology for Nonferrous Metals and Materials, Guilin University of Technologie, Laboratoire de Génie Electrique et Ferroélectricité ( LGEF ), Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université de Lyon-Institut National des Sciences Appliquées ( INSA ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université de Bordeaux ( UB ), Service de Pédiatrie, Centre Hospitalier Universitaire de Nice ( CHU Nice ) -Hôpital l'Archet, Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre Hospitalier de Versailles ( CHV ), Service de neurologie, Hôpital Sainte-Anne, Functional Exploration of Nervous, CHU Grenoble, Service de Neurologie [Rennes], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière ( NEMESIS-CRICM ), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière ( CRICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Français de Mécanique Avancée ( IFMA ), Neurologie - Côte Basque ( NEUROLOGIE ), Hopital, Laboratoire d'Intégration des Systèmes et des Technologies ( LIST ), Université Paris-Saclay-Direction de Recherche Technologique (CEA) ( DRT (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) ( GGB ), Institut Brestois Santé Agro Matière ( IBSAM ), Université de Brest ( UBO ) -Université de Brest ( UBO ) -EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CIC Brest, Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital de la Cavale Blanche, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), CHU Strasbourg, Imagerie cérébrale et handicaps neurologiques, Institut des sciences du cerveau de Toulouse. ( ISCT ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès ( UT2J ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès ( UT2J ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Neurology, Asklepios Klinik Altona, Department of Neurology and Stroke Center, Universität Duisburg-Essen [Essen], Department of Neurology, University of Mainz, Vivantes Klinikum Neukölln, University of Erlangen, University Hospital Münster, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] ( UKE ), PROTOMED, Neurology Department, Ichilov Medical Center, Internal and Cardiovascular Medicine - Stroke Unit ( PERUGIA - ICM-SU ), Università degli Studi di Perugia ( UNIPG ), University Hospital San Raffaele Milan, Scientific Institute and University Ospedale San Raffaele, Dipartimento di Scienze Fisiche, della Terra e dell'Ambiente., Università degli Studi di Siena ( UNISI ), Department of Education, Yamagata University, Nippon Medical School, Catalan Institute of Ornithology (ICO), Museu de Ciències Naturals (Zoologia), Wroclaw University of Science and Technology, Department of neurology, Jagiellonian University [Krakow] ( UJ ), LInguistique et DIdactique des Langues Étrangères et Maternelles ( LIDILEM ), Université Stendhal - Grenoble 3-Université Grenoble Alpes ( UGA ), Metacohorts Consortium, GenXpro GmBH, Lausanne University Hospital, Lausanne university hospital, Northeastern University [Boston], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Cerebral and Cardiovascular Center (NCCC - OSAKA), Department of Neurology (Dep Neuro - BEIJING), Bulgarian Academy of Sciences (BAS), University of Western Ontario (UWO), Servicio de Neurologia (SANTIAGO - Neurologie), Universidad del Desarrollo, Institut de Chimie de Clermont-Ferrand (ICCF), SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Shanghai Polytechnic University (SSPU), Cryogenics Laboratory (CRYOGENICS LABORATORY), Huazhong University of Science and Technology [Wuhan] (HUST)-Wuhan University [China], Centre for Synthetic and Systems Biology (Ssynthsys), University of Edinburgh, Duke University [Durham], National University of Defense Technology [China], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Bordeaux (UB), Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier de Versailles André Mignot (CHV), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut Français de Mécanique Avancée (IFMA), Neurologie - Côte Basque (NEUROLOGIE), Centre hospitalier universitaire de Nantes (CHU Nantes), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Internal and Cardiovascular Medicine - Stroke Unit (PERUGIA - ICM-SU), Università degli Studi di Perugia (UNIPG), Università degli Studi di Siena = University of Siena (UNISI), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurologie - Côte Basque, Centre Hospitalier de la Côte Basque (CHCB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Università degli Studi di Perugia = University of Perugia (UNIPG), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-SIGMA Clermont (SIGMA Clermont), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Jagiellonian University [Krakow] (UJ), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Weimar, Christian (Beitragende*r), and Calvez, Ghislaine

Subjects
Male, Risk, Ticagrelor, Adenosine, [SDV]Life Sciences [q-bio], Population, Medizin, Hemorrhage, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Platelet aggregation inhibitors, Physiology (medical), [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Humans, Myocardial infarction, education, Stroke, ComputingMilieux_MISCELLANEOUS, Aged, Aspirin, Ischemic attack, Transient, Female, Ischemic Attack, Transient, Purinergic P2Y Receptor Antagonists, Treatment Outcome, Cardiology and Cardiovascular Medicine, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [ SDV ] Life Sciences [q-bio], Ischemic Attack, business.industry, medicine.disease, Clopidogrel, [SDV] Life Sciences [q-bio], Anesthesia, Platelet aggregation inhibitor, business, 030217 neurology & neurosurgery, TIMI, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract

Background: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52–1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01994720.

Published
2017

4. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Author

Hauser, Stephen L., Bar-Or, Amit, Comi, Giancarlo, Giovannoni, Gavin, Hartung, Hans-Peter, Hemmer, Bernhard, Lublin, Fred, Montalban, Xavier, Rammohan, Kottil W., Selmaj, Krzysztof, Traboulsee, Anthony, Wolinsky, Jerry S., Arnold, Douglas L., Klingelschmitt, Gaelle, Masterman, Donna, Fontoura, Paulo, Belachew, Shibeshih, Chin, Peter, Mairon, Nicole, Garren, Hideki, Kappos, Ludwig, And Opera Ii Clinical Investigators, Opera I., Reingold, Stephen C., Sandberg-Wollheim, Magnhild, Barkhof, Frederik, Dörmer, Thomas, Evans, Scott, Mcfarland, Henry F., Steiner, Israel, Yaldizli, Özgür, D Souza, Marcus, Andelova, Michaela, Rust, Heiko, Ballario, Carlos, Giannaula, Rolando, Reich, Edgardo Gabriel, Parratt, John, Eggers, Christian, Buyle, Maarten, Pesch, Vincent, Vanopdenbosch, Ludo, Carneiro, Denise, Friedrich, Mauricio, Longo, Alexandre Luiz, Genov, Krasimir, Ivanova, Sonya, Maslarov, Dimitar, Lilovski, Hristo, Staikov, Ivan, Cueto, German, Dufek, Michal, Havrdova, Eva, Novotna, Alena, Skoda, Ondrej, Talabova, Marika, Vachova, Marta, Gross-Paju, Katrin, Haldre, Sulev, Elovaara, Irina, Brochet, Bruno, Castelnovo, Giovanni, Clavelou, Pierre, Seze, Jerome, Debouverie, Marc, Braune, Stefan, Haas, Judith, Heidenreich, Fedor, Schwarz, Wolfgang, Siever, Arno, Urban, Peter Paul, Zettl, Uwe, Ziemann, Ulf, Ziemssen, Tjalf, Zipp, Frauke, Debreczeni, Robert, Rozsa, Csilla, Satori, Maria, Chapman, Joab, Ghezzi, Angelo, Perini, Paola, Pozzilli, Carlo, Kalnina, Jolanta, Millers, Andrejs, Budrys, Valmantas, Kizlaitiene, Rasa, Malciene, Lina, Vaitkus, Antanas, Castro Farfan, Guillermo, Gongora Rivera, Juan Fernando, Frequin, S. T. F. M., Gavidia Chucan, Jorge Martin, Perez Villegas, Julio, Pretell, Edwin Javier, Rodriguez Kadota, Liliana Elizabe, Fryze, Waldemar, Hertmanowska, Hanka, Maciejowski, Maciej, Opala, Grzegorz, Cerqueira, João, Arefieva, Elena, Maslova, Natalia, Odinak, Miroslav, Pankratov, Evgeny, Perfiliev, Semen, Poverennova, Irina, Sazonov, Denis, Shirshova, Elena, Sivertseva, Stella, Volkova, Larisa, Vorobyova, Olga, Knezevic, Zorica, Raicevic, Ranko, Vojinovic, Slobodan, Hancinova, Viera, Saffova, Patricia, Turcani, Peter, Vyletelka, Juraj, Coetzee, Christo C., Garcia-Merino, Antonio, Hernandez, Miguel A., Izquierdo Ayuso, Guillermo, Rodriguez Antigüedad, Alfredo, Gobbi, Claudio, Belal, Samir, Frih-Ayed, Mahbouba, Gouider, Riadh, Mrissa, Ridha, Sergii Moskovko, Sanotskyy, Yanosh, Sokolova, Larysa, Statinova, Olena, Voloshyna, Nataliya, Turner, Benjamin, Wilson, Martin, Applebee, Angela, Bandari, Daniel, Belkin, Martin, Birnbaum, Gary, Borresen, Thor, Boyd, James, Cascione, Mark, Cohan, Stanley, Cohen, Bruce, Conway, Jill, Cree, Bruce, Dihenia, Bhupesh, Dissin, Jonathan, Flitman, Stephen, Ford, Corey, Giancarlo, Thomas, Gold, Scott, Green, Barbara, Gwynn, Matthews, Honeycutt, David, Huddlestone, John, Klawiter, Eric, Kohrman, Bruce, Langer-Gould, Annette, Lava, Neil, Lindsey, William, Mitchell, Galen, Naismith, Robert, Nicolas, Joseph, Pardo, Gabriel, Patel, Malti, Porter, John A. H., Racke, Michael, Robertson, Derrick, Rossman, Howard, Schafer, John, Shubin, Richard, Singer, Barry, Smith, Charles, Suski, Valerie, Thrower, Ben, Wilson, Christopher, Wynn, Daniel, Zabad, Rana, Estol, Conrado J., Scarlatti, Annita, Alekseenko, Yuri, Fedulau, Aliaksandr, Kulesh, Sergey, Navumava, Halina, Willekens, Barbara, Alajbegovic, Azra, Sinanovic, Osman, Christo, Paulo, Papais Alvarenga, Regina Maria, Pereira Damasceno, Benito, Baldaranov, Dimo, Grigorova, Olga, Haralanov, Lyubomir, Milanova, Milena, Ayotte, Charles, Blevins, Gregg, Freedman, Mark, Grand Maison, François, Jacques, François, Yeung, Michael, Basic, Silvio, Hajnsek, Sanja, Janko-Labinac, Dolores, Kidjemet Piskac, Spomenka, Benesova, Yvonne, Hradilek, Pavel, Brassat, David, Edan, Gilles, Hautecoeur, Patrick, Moreau, Thibault, Papeix, Caroline, Tourbah, Ayman, Vukusic, Sandra, Aktas, Orhan, Berthele, Achim, Bodenschatz, Ralf, Foerch, Christian, Hohlfeld, Reinhard, Landefeld, Harald, Lang, Michael, Platten, Michael, Puzich, Reinhard, Schmidt, Stephan, Tubridy, Niall, Ardito, Bonaventura, Capra, Ruggero, Centonze, Diego, Crociani, Paola, Danni, Maura, Grimaldi, Luigi, Gusmaroli, Graziano, Mantegazza, Renato, Mirabella, Massimiliano, Uccelli, Antonio, Carbajal Ramirez, Angelica, Lopez Meza, Elmer Guillermo, Lopez Prieto, Juan Jose, Oropeza Alba, Jose Luis, Reyes-Morales, Sarug, San Juan Orta, Daniel, Myhr, Kjell Morten, Binek, Maciej, Czarnecki, Maciej, Klodowska-Duda, Gabriela, Stelmasiak, Zbigniew, Szczudlik, Andrzej, Tutaj, Andrzej, Belova, Anna, Dorogov, Nikolay, Fedyanin, Alexander, Khasanova, Dina, Makarov, Nikolay, Mishin, Gennadiy, Sherman, Mikhail, Skoromets, Alexander, Trushnikova, Tatiana, Donath, Vladimir, Dupejova, Beata, Gurcik, Ladislav, Arroyo, Rafael, Andres, Clara, Fernandez Fernandez, Oscar, Lainez Andrep, Jose Miguel, Martinez Gines, Maria Luisa, Martinez Rodriguez, Jose Enrique, Martinez Yelamos, Sergio, Oreja Guevara, Celia, Perez Sempere, Angel, Ramio, Luis, Ramo Tello, Cristina, Lycke, Jan, Olsson, Tomas, Roshanisefat, Homayoun, Sundström, Peter, Svenningsson, Anders, Akman Demir, Gulsen, Petek Balci, Belgin, Boz, Cavit, Efendi, Husnu, Karabudak, Rana, Siva, Aksel, Terzi, Murat, Yuceyar, Ayse Nur, Chmyr, Galyna, Goncharova, Yana, Kareta, Serhiy, Lutskiy, Igor, Harrower, Timothy, Hawkins, Clive, Pearson, Owen, Silber, Eli, Absher, John, Arnold, Thomas, Bass, Ann, Bernitsas, Evanthia, Braley, Tiffany, Calkwood, Jonathan, Carnes, Kenneth, Coyle, Patricia, Dunn, Jeffrey, Edwards, Keith, English, Jeffrey, Ferencz, Gerald, Fox, Edward, Frohman, Elliott, Gazda, Suzanne, Gitt, Jeffrey, Goodman, Andrew, Gross, Jeffrey, Hendin, Barry, Herrman, Craig, Hillen, Machteld, Huang, Deren, Hunter, Samuel, Hutton, George, Jacobs, Daniel, Keller, Bridget, Khan, Omar, Kister, Ilya, Krupp, Lauren, Lathi, Ellen, Lynch, Sharon, Miller, Tamara, Miravalle, Augusto, Omidvar, Omid, Perumal, Jai, Picone, Maryann, Rao, T. Hemanth, Repovic, Pavle, Riskind, Peter, Rowe, Vernon, Sheremata, William, Steingo, Brian, Twyman, Cary, Weisman, David, Wendt, Jeanette, Wray, Sibyl, Yapundich, Robert, Zarif, Myassar, Lääketieteen ja biotieteiden tiedekunta - Faculty of Medicine and Life Sciences, Tampere University, Hauser, S. L., Bar or, A., Comi, Giancarlo, Giovannoni, G., Hartung, H. . P., Hemmer, B., Lublin, F., Montalban, X., Rammohan, K. W., Selmaj, K., Traboulsee, A., Wolinsky, J. S., Arnold, D. L., Klingelschmitt, G., Masterman, D., Fontoura, P., Belachew, S., Chin, P., Mairon, N., Garren, H., Kappos, L., Universidade do Minho, Willekens, Barbara, and OPERA I and OPERA II Clinical Investigators

Subjects
0301 basic medicine, Male, Esclerosi múltiple, Adult, Antibodies, Monoclonal, Humanized, Antigens, CD20, B-Lymphocytes, Brain, Disease Progression, Female, Humans, Immunologic Factors, Infusions, Intravenous, Interferon-beta, Magnetic Resonance Imaging, Middle Aged, Multiple Sclerosis, Relapsing-Remitting, Recurrence, Medicine (all), Relapsing-Remitting, Gastroenterology, Medicina Clínica [Ciências Médicas], law.invention, 0302 clinical medicine, Immunologic Factor, Randomized controlled trial, law, Monoclonal, Clinical endpoint, Infusions, Intravenou, Immunologia, Humanized, Hazard ratio, B-Lymphocyte, General Medicine, Settore MED/26 - Neurologia, Intravenous, Neurotieteet - Neurosciences, medicine.drug, Human, medicine.medical_specialty, Infusions, Multiple Sclerosis, Immunology, Antibodies, Multiple sclerosis, 03 medical and health sciences, Internal medicine, medicine, CD20, Antigens, Ciências Médicas::Medicina Clínica, business.industry, Interferon beta-1a, medicine.disease, Confidence interval, Ocrelizumab, Interferon Beta-1a, Relapsing Multiple Sclerosis, 030104 developmental biology, Monoclonal antibodies, Human medicine, business, Anticossos monoclonals, 030217 neurology & neurosurgery
Abstract

BACKGROUND B cells influence the pathogenesis of multiple sclerosis. Ocrelizumab is a humanized monoclonal antibody that selectively depletes CD20+ B cells. METHODS In two identical phase 3 trials, we randomly assigned 821 and 835 patients with relapsing multiple sclerosis to receive intravenous ocrelizumab at a dose of 600 mg every 24 weeks or subcutaneous interferon beta-1a at a dose of 44 mu g three times weekly for 96 weeks. The primary end point was the annualized relapse rate. RESULTS The annualized relapse rate was lower with ocrelizumab than with interferon beta-1a in trial 1 (0.16 vs. 0.29; 46% lower rate with ocrelizumab; P, info:eu-repo/semantics/publishedVersion

Published
2017

5. How does fingolimod (gilenya(®)) fit in the treatment algorithm for highly active relapsing-remitting multiple sclerosis?

Author

Larysa Sokolova, Peter Turcani, Radomír Taláb, Eva Havrdova, Panayiotis Panayiotou, Franz Fazekas, Tetiana Kobys, Gábor Jakab, Sergii Moskovko, Theodoros Kyriakides, Sámuel Komoly, Thomas Berger, Egon Kurča, Nataliya Voloshyná, Jörg Kraus, Karl Vass, Norbert Vella, Saša Šega Jazbec, Latchezar Traykov, Ovidiu Bajenaru, Ivan Milanov, Alenka Horvat Ledinek, Tanja Hojs Fabjan, L'ubomír Lisý, and Tetyana Nehrych

Subjects
Oral treatment, Disease, Neurological disorder, multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Hypothesis and Theory, medicine, 030212 general & internal medicine, fingolimod, algorithm, treatment, business.industry, Multiple sclerosis, medicine.disease, Fingolimod, 3. Good health, expert opinion, Eastern european, Neurology, Relapsing remitting, Multiple sclerosis -- Case studies, Expert opinion, Neurology (clinical), business, Algorithm, Multiple sclerosis -- Treatment, Algorithms, 030217 neurology & neurosurgery, medicine.drug, Neuroscience
Abstract

Multiple sclerosis (MS) is a neurological disorder characterized by inflammatory demyelination and neurodegeneration in the central nervous system. Until recently, disease-modifying treatment was based on agents requiring parenteral delivery, thus limiting long-term compliance. Basic treatments such as beta-interferon provide only moderate efficacy, and although therapies for second-line treatment and highly active MS are more effective, they are associated with potentially severe side effects. Fingolimod (Gilenya®) is the first oral treatment of MS and has recently been approved as single disease-modifying therapy in highly active relapsing-remitting multiple sclerosis (RRMS) for adult patients with high disease activity despite basic treatment (beta-interferon) and for treatment-naïve patients with rapidly evolving severe RRMS. At a scientific meeting that took place in Vienna on November 18th, 2011, experts from ten Central and Eastern European countries discussed the clinical benefits and potential risks of fingolimod for MS, suggested how the new therapy fits within the current treatment algorithm and provided expert opinion for the selection and management of patients., peer-reviewed

Published
2012

6. Placebo-controlled trial of oral laquinimod for multiple sclerosis

Author

Waldemar Brola, Sergii Moskovko, Massimo Filippi, Arnonk Karni, Elzbieta Jasinska, Tetyana Nehrych, Xavier Montalban, Luis Brieva Ruiz, Alexei Boyko, Ivan Milanov, Giulia Longoni, Pille Taba, Martina Absinta, Maria A Rocca, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), ALLEGRO Study Group, Comi, Giancarlo, Jeffery, D, Kappos, L, Montalban, X, Boyko, A, Rocca, Ma, Filippi, Massimo, and for the ALLEGRO Study, Group

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Placebo-controlled study, Pain, Phases of clinical research, Quinolones, Relapsing-Remitting, Placebo, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Double-Blind Method, Relapsing-Remitting/*drug therapy/pathology, Pain/chemically induced, Internal medicine, Clinical endpoint, Medicine, Humans, 030304 developmental biology, 0303 health sciences, Quinolones/adverse effects/*therapeutic use, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Brain, General Medicine, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Surgery, Clinical trial, Cough, chemistry, Disease Progression, Settore MED/26 - Neurologia, Female, Multiple Sclerosis, Relapsing-Remitting, business, Laquinimod, 030217 neurology & neurosurgery, Brain/*pathology, Cough/chemically induced
Abstract

Comi, Giancarlo Jeffery, Douglas Kappos, Ludwig Montalban, Xavier Boyko, Alexey Rocca, Maria A Filippi, Massimo ALLEGRO Study Group Clinical Trial, Phase III Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't United States The New England journal of medicine N Engl J Med. 2012 Mar 15;366(11):1000-9.; BACKGROUND: Two proof-of-concept clinical trials have provided evidence that laquinimod reduces disease activity in patients with relapsing-remitting multiple sclerosis. METHODS: We conducted a randomized, double-blind, phase 3 study at 139 sites in 24 countries. A total of 1106 patients with relapsing-remitting multiple sclerosis were randomly assigned in a 1:1 ratio to receive oral laquinimod at a dose of 0.6 mg once daily or placebo for 24 months. The primary end point was the annualized relapse rate during the 24-month period. Secondary end points included confirmed disability progression (defined as an increase in the score on the Expanded Disability Status Scale that was sustained for at least 3 months) and the cumulative number of gadolinium-enhancing lesions and new or enlarging lesions on T(2)-weighted magnetic resonance imaging. RESULTS: Treatment with laquinimod as compared with placebo was associated with a modest reduction in the mean (+/-SE) annualized relapse rate (0.30+/-0.02 vs. 0.39+/-0.03, P=0.002) and with a reduction in the risk of confirmed disability progression (11.1% vs. 15.7%; hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; P=0.01). The mean cumulative numbers of gadolinium-enhancing lesions and new or enlarging lesions on T(2)-weighted images were lower for patients receiving laquinimod than for those receiving placebo (1.33+/-0.14 vs. 2.12+/-0.22 and 5.03+/-0.08 vs. 7.14+/-0.07, respectively; P

Published
2012
Full Text
View/download PDF

7. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis

Author

Montalban, Xavier, Hauser, Stephen L., Kappos, Ludwig, Arnold, Douglas L., Bar-Or, Amit, Comi, Giancarlo, Seze, Jérôme, Giovannoni, Gavin, Hartung, Hans-Peter, Hemmer, Bernhard, Lublin, Fred, Rammohan, Kottil W., Selmaj, Krzysztof, Traboulsee, Anthony, Sauter, Annette, Masterman, Donna, Fontoura, Paulo, Belachew, Shibeshih, Garren, Hideki, Mairon, Nicole, Chin, Peter, Wolinsky, Jerry S., Oratorio, Clinical Investigators, Reingold, Stephen C., Sandberg-Wollheim, Magnhild, Barkhof, Frederik, Dörner, Thomas, Evans, Scott, Mcfarland, Henry F., Steiner, Israel, Yaldizli, Özgür, D Souza, Marcus, Andelova, Michaela, Rust, Heiko, Sedal, Leslie, Taylor, Bruce, Assar, Hamid, Auff, Eduard, Berger, Thomas, Guger, Michael, Pilz, Georg, Wipfler, Peter, Bartholomé, Emmanuel, Decoo, Danny, Becker, Jefferson, Da Silva Filho, Irenio, Diniz, Denise, Gomes Neto, Antônio, Leon, Soniza, Haralanov, Lyubomir, Milanov, Ivan, Bar-Or, Amir, Freedman, Mark, Grand Maison, François, Marriott, James, O Connor, Paul, Selchen, Daniel, Yeung, Michael, Benesova, Yvonne, Krasulova, Eva, Vachova, Marta, Airas, Laura, Elovaara, Irina, Färkkilä, Markus, Korpela, Jaana, Sumelahti, Marja-Liisa, Brassat, David, Brochet, Bruno, Camu, William, Castelnovo, Giovanni, Clanet, Michel, Clavelou, Pierre, Debouverie, Marc, Defer, Giles, Gout, Olivier, Heinzlef, Olivier, Laplaud, David, Lebrun-Frenay, Christine, Papeix, Caroline, Pelletier, Jean, Tourbah, Ayman, Vermersch, Patrick, Vukusic, Sandra, Angstwurm, Klemens, Berghoff, Martin, Förch, Christian, Goebels, Norbert, Haas, Judith, Harms, Lutz, Kleiter, Ingo, Koehler, Jürgen, Lensch, Eckard, Limmroth, Volker, Meuth, Sven, Oschmann, Patrick, Platten, Michael, Then Bergh, Florian, Tumani, Hayrettin, Ziemann, Ulf, Ziemssen, Tjalf, Afradou, Theodora, Fakas, Nikolaos, Tsounis, Stefanos, Vlaikidis, Nikolaos, Jakab, Gábor, Komoly, Sámuel, Rózsa, Csilla, Sátori, Mária, Szabó, Gyöngyi, Vécsei, László, Achiron, Anat, Hellmann, Mark, Karni, Arnon, Karussis, Dimitrios, Milo, Ron, Shahien, Radi, Bertolotto, Antonio, Marrosu, Maria Giovanna, Uccelli, Antonio, Malciene, Lina, Rastenyte, Daiva, Sceponaviciute, Sigla, Castro Farfan, Freddy, Duriez Sotelo, Eduardo, Flores-Rivera, Jose, Reyes Morales, Sarug, Hintzen, Rogier, Hupperts, Raymond, Lynch, Christopher, Mossman, Stuart, Gulowsen Celius, Elisabeth, Gavidia Chucan, Jorge, Perez Villegas, Julio, Pretell Alva, Edwin, Bielecki, Dariusz, Brola, Waldemar, Kochanowicz, Jan, Maciejowski, Maciej, Stelmasiak, Zbigniew, Zbrojkiewicz, Janusz, Cunha, Luis, Gonçalves, José, Mendes, Irene, Sá, João, Salgado, Vasco, Silva, Ana, Balasa, Rodica, Manescu, Silviu, Panea, Cristina Aura, Simu, Mihaela Adriana, Yakupov, Eduard, Álvarez Cermeño, José, Álvarez Cermeño, Carlos, Arroyo, Rafael, Escartín Siquier, Antonio, Fernández, Oscar, Izquierdo Ayuso, Guillermo, Martinez Rodríguez, José Enrique, Fernandez Sanchez, Victoria, Olascoaga Urtaza, Francisco Javier, Meca, Virginia, Olascoaga, Javier, Oreja-Guevara, Celia, Perez Sempere, Angel, Prieto González, José María, Ramió Torrentá, Lluis, Rodríguez-Antigüeda, Alfredo, Saiz, Albert, Gobbi, Claudio, Kuhle, Jens, Galusha, Anatoliy, Goloborodko, Alla, Litovchenko, Tetyana, Moroz, Olena, Sergii Moskovko, Nehrych, Tetyana, Pashkovskyy, Valeriy, Shkolnyk, Valerii, Shulga, Olga, Sokolova, Larysa, Voloshyna, Nataliya, Brex, Peter, Constantinescu, Cris, Duddy, Martin, Schmierer, Klaus, Young, Carolyn, Agius, Mark, Ash, Paul, Bandari, Daniel, Belkin, Martin, Bernitsas, Evanthia, Bowen, James, Cahill, Jonathan, Carpenter, Adam, Carter, Jonathan, Cerghet, Mirela, Conway, Jill, Cooper, Joanna, Coyle, Patricia, Cross, Anne, Ford, Corey, Fox, Edward, Freedman, S. Mitchell, Frohman, Elliot, Gitt, Jeffrey, Gottesman, Malcolm, Gudesblatt, Mark, Hendin, Barry, Hutton, George, Klineova, Sylvia, Krupp, Lauren, Lynch, Sharon, Markowitz, Clyde, Mattson, David, Miller, Aaron, Miravalle, Augusto, Muley, Suraj, Nealon, Nancy, Pardo, Gabriel, Picone, Mary Ann, Racke, Michael, Rizvi, Syed, Rossman, Howard, Rowe, Vernon, Schulman, Alan, Shafer, Stuart, William, Sheremata, Stein, Lee, and Waubant, Emmanuelle

8. Quality of Life in Patients with Multiple Sclerosis: Therapeutic Effect of Cholecalciferol (Vitamin D3) ; Качество жизни больных с множественным склерозом: терапевтическое влияние холекальциферола (витамина D3) ; Якість життя хворих із множинним склерозом: терапевтичний вплив холекальциферолу (вітаміну D3)

Author

Malyk, S. L., Sergii Moskovko, Moskovko, H. S., and Tytarenko, N. V.

9. Placebo-controlled trial of oral laquinimod in multiple sclerosis: MRI evidence of an effect on brain tissue damage

Author

Elisabetta Pagani, Waldemar Brola, Sergii Moskovko, Massimo Filippi, Arnonk Karni, Nicola De Stefano, Elzbieta Jasinska, Tetyana Nehrych, Xavier Montalban, Luis Brieva Ruiz, Krzysztof Selmaj, Alexei Boyko, Ivan Milanov, Giulia Longoni, Pille Taba, Martina Absinta, Maria A Rocca, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Università degli Studi di Siena = University of Siena (UNISI), Cornerstone Health Care, North Carolina, USA, Clinical Neuroimmunology, Department of Biomedicine, University of Basel, Basel, Vall d'Hebron University Hospital [Barcelona], Department of Neurology and Neurosurgery, Russian State Medical University and Moscow MS Center, Moscow, Edan, Gilles, Filippi, Massimo, Rocca, Ma, Pagani, E, De Stefano, N, Jeffery, D, Kappos, L, Montalban, X, Boyko, An, Comi, Giancarlo, and on behalf of the ALLEGRO Study, Group

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Magnetic Resonance Spectroscopy, Multiple Sclerosis, Adolescent, Endpoint Determination, Placebo-controlled study, Grey matter, Quinolones, Placebo, Gastroenterology, White matter, chemistry.chemical_compound, Disability Evaluation, Young Adult, Atrophy, Thalamus, MRI, Internal medicine, medicine, Image Processing, Computer-Assisted, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aspartic Acid, medicine.diagnostic_test, business.industry, Multiple sclerosis, Brain, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, medicine.anatomical_structure, Treatment Outcome, chemistry, Creatinine, Surgery, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Settore MED/26 - Neurologia, Neurology (clinical), business, Laquinimod
Abstract

TRIAL REGISTRATION: The ALLEGRO trial identifier number with clinicaltrials.gov is NCT00509145.; International audience; OBJECTIVE: In Assessment of OraL Laquinimod in PrEventing ProGRession in Multiple SclerOsis (ALLEGRO), a phase III study in relapsing-remitting multiple sclerosis (RRMS), oral laquinimod slowed disability and brain atrophy progression, suggesting laquinimod may reduce tissue damage in MS. MRI techniques sensitive to the most destructive aspects of the disease were used to further investigate laquinimod's potential effects on inflammation and neurodegeneration.METHODS: 1106 RRMS patients were randomised 1:1 to receive once-daily oral laquinimod (0.6 mg) or placebo for 24 months. White matter (WM), grey matter (GM) and thalamic fractions were derived at months 0, 12 and 24. Also assessed were evolution of gadolinium-enhancing and/or new T2 lesions into permanent black holes (PBH); magnetisation transfer ratio (MTR) of normal-appearing brain tissue (NABT), WM, GM and T2 lesions; and N-acetylaspartate/creatine (NAA/Cr) levels in WM.RESULTS: Compared with placebo, laquinimod-treated patients showed lower rates of WM at months 12 and 24 (p=0.004 and p=0.035) and GM (p=0.004) atrophy at month 12 and a trend for less GM atrophy at month 24 (p=0.078). Laquinimod also slowed thalamic atrophy at month 12 (p=0.005) and month 24 (p=0.003) and reduced the number of PBH at 12 and 24 months evolving from active lesions (all p

Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results