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3. Case report: Hyponatremia is an initial presentation of Neuromyelitis optica spectrum disorder.

Author

Meng, Huaxing, Wang, Jing, Hou, Jiaqi, Liu, Ruiqin, and Zhang, Meini

Abstract

Objective: Neuromyelitis optica spectrum disorders (NMOSD) is often misdiagnosed or delayed because of the complex and diverse clinical manifestations, especially the atypical initial presentation. Hyponatremia can be an infrequently isolated initial presentation of NMOSD and is associated with hypothalamus involvement. Awareness of this mechanism will help clinicians to identify NMOSD early, treat it in time and improve the prognosis. Methods: We describe a 36-year-old woman who developed repeated hyponatremia and then experienced diplopia. Serum AQP4, MOG, MBP and GFAP antibody were detected, and NMOSD was finally diagnosed. Results: She responded well to high-dose glucocorticoids. Sequential treatment with mycophenolate mofetil (MMF) was prescribed. Two-month follow-up revealed full recovery. So far, after 10 months, the patient still has no recurrence. Conclusion: For young patients, repeated hyponatremia, with or without slight fever, and no evidence of obvious infection, brain magnetic resonance imaging (MRI) and serum AQP4/MOG antibody detection may be useful to determine whether there is a possibility of NMOSD. [ABSTRACT FROM AUTHOR]

Published
2024
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4. A multicenter, randomized, open‐label, phase 2 clinical study of telitacicept in adult patients with generalized myasthenia gravis

Author

Yin, Jian, primary, Zhao, Mingming, additional, Xu, Xianhao, additional, Zhang, Meini, additional, Xu, Zucai, additional, Li, Zunbo, additional, Qin, Xinyue, additional, Li, Zhuyi, additional, Zhao, Chongbo, additional, Zhou, Hongyu, additional, Ma, Ying, additional, Cao, Wenfeng, additional, Wang, Guoping, additional, Lin, Yongzhong, additional, Zhang, Jizhong, additional, Zhang, Xu, additional, Cai, Hongbin, additional, Qian, Weidong, additional, Wang, Yiqi, additional, Zhang, Xinghu, additional, Liu, Guangzhi, additional, Wang, Jiawei, additional, Qiu, Wei, additional, Min, Lianqiu, additional, Li, Jing, additional, Deng, Hui, additional, Chu, Lan, additional, Zhang, Yifan, additional, and Fang, Jianmin, additional

Published
2024
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5. Safety and efficacy of teriflunomide in paediatric multiple sclerosis (TERIKIDS): a multicentre, double-blind, phase 3, randomised, placebo-controlled trial

Author

Dubois, Benedicte, Verhelst, Helene, Bojinova-Tchamova, Veneta, Mah, Jean, Cui, Li-Ying, Fang, Fang, Hao, Yunpeng, Jiang, Li, Li, Ling, Mao, Ding'An, Qiu, Wei, Tan, Guojun, Wu, Ye, Zhang, Meini, Zhou, Hongyu, Zhou, Shuizhen, Gross-Paju, Katrin, Cheuret, Emmanuel, Deiva, Kumaran, Edan, Giles, Vukusic, Sandra, Chrousos, George, Zafeiriou, Dimitrios, Achiron, Anat, Vaknin-Dembinsky, Adi, Yamout, Bassem, Laurynaitiene, Jurate, Vaiciene-Magistris, Nerija, Bojkovski, Vladimir, Trajkova, Vesna, Chaouki, Sana, Kissani, Najib, Neuteboom, Rinze, Palavra, Filipe, Belova, Anna, Boyko, Alexey, Evdoshenko, Evgeny, Kairbekova, Ekaterina, Malkova, Nadezhda, Shumilina, Maria, Skripchenko, Natalya, Nikolic, Dimitrije, Meca-Lallana, Jose, Triki, Chahnez Charfi, Chokri, Mhiri, Gouider, Riadh, Anlar, Banu, Gücüyener, Kivilcim, Hiz, Ayse Semra, Idiman, Egemen, Turkoglu, Recai, Yapici, Zuhal, Yilmaz, Unsal, Tantsura, Lyudmyla, Voloshyna, Nataliia, Lim, Ming, Wassmer, Evangeline, Cascione, Mark, Chitnis, Tanuja, LaGanke, Christopher, Rathke, Kevin, Scagnelli, John, Banwell, Brenda, Kappos, Ludwig, Arnold, Douglas L, Skripchenko, Natalia, Saubadu, Stephane, Hu, Wenruo, Benamor, Myriam, Le-Halpere, Annaig, Truffinet, Philippe, and Tardieu, Marc

Published
2021
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9. Safety of teriflunomide in Chinese adult patients with relapsing multiple sclerosis: A phase IV, 24-week multicenter study

Author

Quan, Chao, primary, Zhou, Hongyu, additional, Yang, Huan, additional, Jiao, Zheng, additional, Zhang, Meini, additional, Zhang, Baorong, additional, Tan, Guojun, additional, Bu, Bitao, additional, Jin, Tao, additional, Li, Chunyang, additional, Xue, Qun, additional, Dong, Huiqing, additional, Shi, Fudong, additional, Qin, Xinyue, additional, Zhang, Xinghu, additional, Gao, Feng, additional, Zhang, Hua, additional, Wang, Jiawei, additional, Hu, Xueqiang, additional, Chen, Yueting, additional, Liu, Jue, additional, and Qiu, Wei, additional

Published
2024
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11. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study

Author

Achiron, Anat, Achtnichts, Lutz, Agan, Kadriye, Akman-Demir, Gulsen, Allen, Alison B, Antel, Jack P, Antiguedad, Alfredo Rodriguez, Apperson, Michelle, Applebee, Angela M, Ayuso, Guillermo Izquierdo, Baba, Masayuki, Bajenaru, Ovidiu, Balasa, Rodica, Balci, Belgin Petek, Barnett, Michael, Bass, Ann, Becker, Veit U, Bejinariu, Mihaela, Bergh, Florian Then, Bergmann, Arnfin, Bernitsas, Evanthia, Berthele, Achim, Bhan, Virender, Bischof, Felix, Bjork, Randall John, Blevins, Gregg, Boehringer, Matthias, Boerner, Thomas, Bonek, Robert, Bowen, James D, Bowling, Allen, Boyko, Alexey N, Boz, Cavit, Bracknies, Vera, Braune, Stefan, Brescia Morra, Vincenzo, Brochet, Bruno, Brola, Waldemar, Brownstone, Paul Kenneth, Brozman, Miroslav, Brunet, Donald, Buraga, Ioan, Burnett, Margaret, Buttmann, Mathias, Butzkueven, Helmut, Cahill, Jonathan, Calkwood, Jonathan C, Camu, William, Cascione, Mark, Castelnovo, Giovani, Centonze, Diego, Cerqueira, Joao, Chan, Andrew, Cimprichova, Andrea, Cohan, Stanley, Comi, Giancarlo, Conway, Jill, Cooper, Joanna A, Corboy, John, Correale, Jorge, Costell, Brian, Cottrell, David A, Coyle, Patricia K, Craner, Matthew, Cui, Liying, Cunha, Luis, Czlonkowska, Anna, da Silva, Ana Martins, de Sa, Joao, de Seze, Jérôme, Debouverie, Marc, Debruyne, Jan, Decoo, Danny, Defer, Gilles, Derfuss, Tobias, Deri, Norma H, Dihenia, Bhupesh, Dioszeghy, Peter, Donath, Vladimir, Dubois, Benedicte, Duddy, Martin, Duquette, Pierre, Edan, Gilles, Efendi, Husnu, Elias, Stanton, Emrich, Peter J, Estruch, Bonaventura Casanova, Evdoshenko, Evgeniy P, Faiss, Juergen, Fedyanin, Alexander S, Feneberg, Wolfgang, Fermont, Jiske, Fernandez, Oscar Fernandez, Ferrer, Francisco Coret, Fink, Katharina, Ford, Helen, Ford, Corey, Francia, Ada, Freedman, Mark, Frishberg, Benjamin, Galgani, Simonetta, Garmany, George P, Gehring, Klaus, Gitt, Jeffrey, Gobbi, Claudio, Goldstick, Lawrence P, Gonzalez, Rafael Arroyo, Grandmaison, Francois, Grigoriadis, Nikolaos, Grigorova, Olga, Grimaldi, Luigi Maria Edoardo, Gross, Jeffrey, Gross-Paju, Katrin, Gudesblatt, Mark, Guillaume, Daniel, Haas, Judith, Hancinova, Viera, Hancu, Anca, Hardiman, Orla, Harmjanz, Arndt, Heidenreich, Fedor R, Hengstman, G J D, Herbert, Joseph, Herring, Mark, Hodgkinson, Suzanne, Hoffmann, Olaf M, Hofmann, Werner E, Honeycutt, William D, Hua, Le Hanh, Huang, Dehui, Huang, Yining, Huang, DeRen, Hupperts, Raymond, Imre, Piroska, Jacobs, Alan Keith, Jakab, Gabor, Jasinska, Elzbieta, Kaida, Kenichi, Kalnina, Jolanta, Kaprelyan, Ara, Karelis, Guntis, Karussis, Dimitrios, Katz, Amos, Khabirov, Farit A, Khatri, Bhupendra, Kimura, Takashi, Kister, Ilya, Kizlaitiene, Rasa, Klimova, Eleonora, Koehler, Juergen, Komatineni, Aparna, Kornhuber, Anselm, Kovacs, Krisztina, Koves, Agnes, Kozubski, Wojciech, Krastev, Georgi, Krupp, Lauren B, Kurca, Egon, Lassek, Christoph, Laureys, Guy, Lee, Liesly, Lensch, Eckart, Leutmezer, Fritz, Li, Hongzeng, Linker, Ralf A, Linnebank, Michael, Liskova, Petra, Llanera, Cristina, Lu, Jiahong, Lutterotti, Andreas, Lycke, Jan, Macdonell, Richard, Maciejowski, Maciej, Maeurer, Mathias, Magzhanov, Rim V, Maida, Eva-Maria, Malciene, Lina, Mao-Draayer, Yang, Marfia, Girolama Alessandra, Markowitz, Clyde, Mastorodimos, Vasileios, Matyas, Klotild, Meca-Lallana, Jose, Merino, Juan Antonio Garcia, Mihetiu, Ioan Gheorghe, Milanov, Ivan, Miller, Aaron E, Millers, Andrejs, Mirabella, Massimiliano, Mizuno, Masanori, Montalban, Xavier, Montoya, Lilina, Mori, Masahiro, Mueller, Stefanie, Nakahara, Jin, Nakatsuji, Yuji, Newsome, Scott, Nicholas, Richard, Nielsen, A Scott, Nikfekr, Esmaeil, Nocentini, Ugo, Nohara, Chiyoko, Nomura, Kyoichi, Odinak, Miroslav M, Olsson, Tomas, van Oosten, B W, Oreja-Guevara, Celia, Oschmann, Patrick, Overell, James, Pachner, Andrew, Panczel, Gyula, Pandolfo, Massimo, Papeix, Caroline, Patrucco, Liliana, Pelletier, Jean, Piedrabuena, Raul, Pless, Misha, Polzer, Udo, Pozsegovits, Krisztian, Rastenyte, Daiva, Rauer, Sebastian, Reifschneider, Gerd, Rey, Roberto, Rizvi, Syed A, Robertson, Derrick, Rodriguez, Jose Martinez, Rog, David, Roshanisefat, Homayoun, Rowe, Vernon, Rozsa, Csilla, Rubin, Susan, Rusek, Stanislaw, Saccà, Francesco, Saida, Takahiko, Salgado, Antonio Vasco, Sanchez, Victoria Eugenia Fernandez, Sanders, Kalina, Satori, Maria, Sazonov, Denis V, Scarpini, Elio Angelo, Schlegel, Eugen, Schluep, Myriam, Schmidt, Stephan, Scholz, Erich, Schrijver, H M, Schwab, Matthias, Schwartz, Raymond, Scott, James, Selmaj, Krzysztof, Shafer, Stuart, Sharrack, Basil, Shchukin, Ivan A, Shimizu, Yuko, Shotekov, Penko, Siever, Arno, Sigel, Karl-Otto, Silliman, Scott, Simo, Magdolna, Simu, Mihaela, Sinay, Vladimiro, Siquier, Antonio Escartin, Siva, Aksel, Skoda, Ondrej, Solomon, Andrew, Stangel, Martin, Stefoski, Dusan, Steingo, Brian, Stolyarov, Igor D, Stourac, Pavel, Strassburger-Krogias, Katrin, Strauss, Erik, Stuve, Olaf, Tarnev, Ivaylo, Tavernarakis, Antonios, Tello, Cristina Ramo, Terzi, Murat, Ticha, Veronika, Ticmeanu, Marina, Tiel-Wilck, Klaus, Toomsoo, Toomas, Tubridy, Niall, Tullman, Mark J, Tumani, Hayrettin, Turcani, Peter, Turner, Ben, Uccelli, Antonio, Urtaza, Francisco Javier Olascoaga, Vachova, Marta, Valikovics, Attila, Walter, Silke, Van Wijmeersch, Bart, Vanopdenbosch, Ludo, Weber, Joerg R, Weiss, Sara, Weissert, Robert, Vermersch, Patrick, West, Timothy, Wiendl, Heinz, Wiertlewski, Sandrine, Wildemann, Brigitte, Willekens, Barbara, Visser, L H, Vorobeychik, Galina, Xu, Xianhao, Yamamura, Takashi, Yang, Yi N, Yelamos, Sergio Martinez, Yeung, Michael, Zacharias, Alan, Zelkowitz, Marvin, Zettl, Uwe, Zhang, Meini, Zhou, Hongyu, Zieman, Ulf, Ziemssen, Tjalf, Kappos, Ludwig, Bar-Or, Amit, Cree, Bruce A C, Fox, Robert J, Giovannoni, Gavin, Gold, Ralf, Arnold, Douglas L, Arnould, Sophie, Scherz, Tatiana, Wolf, Christian, Wallström, Erik, and Dahlke, Frank

Published
2018
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14. Safety and efficacy of teriflunomide in paediatric multiple sclerosis (TERIKIDS): a multicentre, double-blind, phase 3, randomised, placebo-controlled trial

Author

Chitnis, Tanuja, primary, Banwell, Brenda, additional, Kappos, Ludwig, additional, Arnold, Douglas L, additional, Gücüyener, Kivilcim, additional, Deiva, Kumaran, additional, Skripchenko, Natalia, additional, Cui, Li-Ying, additional, Saubadu, Stephane, additional, Hu, Wenruo, additional, Benamor, Myriam, additional, Le-Halpere, Annaig, additional, Truffinet, Philippe, additional, Tardieu, Marc, additional, Dubois, Benedicte, additional, Verhelst, Helene, additional, Bojinova-Tchamova, Veneta, additional, Mah, Jean, additional, Fang, Fang, additional, Hao, Yunpeng, additional, Jiang, Li, additional, Li, Ling, additional, Mao, Ding'An, additional, Qiu, Wei, additional, Tan, Guojun, additional, Wu, Ye, additional, Zhang, Meini, additional, Zhou, Hongyu, additional, Zhou, Shuizhen, additional, Gross-Paju, Katrin, additional, Cheuret, Emmanuel, additional, Edan, Giles, additional, Vukusic, Sandra, additional, Chrousos, George, additional, Zafeiriou, Dimitrios, additional, Achiron, Anat, additional, Vaknin-Dembinsky, Adi, additional, Yamout, Bassem, additional, Laurynaitiene, Jurate, additional, Vaiciene-Magistris, Nerija, additional, Bojkovski, Vladimir, additional, Trajkova, Vesna, additional, Chaouki, Sana, additional, Kissani, Najib, additional, Neuteboom, Rinze, additional, Palavra, Filipe, additional, Belova, Anna, additional, Boyko, Alexey, additional, Evdoshenko, Evgeny, additional, Kairbekova, Ekaterina, additional, Malkova, Nadezhda, additional, Shumilina, Maria, additional, Skripchenko, Natalya, additional, Nikolic, Dimitrije, additional, Meca-Lallana, Jose, additional, Triki, Chahnez Charfi, additional, Chokri, Mhiri, additional, Gouider, Riadh, additional, Anlar, Banu, additional, Hiz, Ayse Semra, additional, Idiman, Egemen, additional, Turkoglu, Recai, additional, Yapici, Zuhal, additional, Yilmaz, Unsal, additional, Tantsura, Lyudmyla, additional, Voloshyna, Nataliia, additional, Lim, Ming, additional, Wassmer, Evangeline, additional, Cascione, Mark, additional, Chitnis, Tanuja, additional, LaGanke, Christopher, additional, Rathke, Kevin, additional, and Scagnelli, John, additional

Published
2021
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17. A multicenter study to evaluate the disease burden and health economics of inpatients with multiple sclerosis in China

Author

Tan, Guojun, Xu, Yan, Wang, Weizhi, Wang, Lihua, Li, Chunyang, Zhang, Xinghu, Zhou, Hongyu, Dong, Huiqing, Zhang, Meini, Jin, Tao, Yang, Huan, Cui, Liying, and Guo, Li

Subjects
China, Inpatients, Cross-Sectional Studies, Multiple Sclerosis, Cost of Illness, Neurology, Humans, Neurology (clinical), General Medicine, Middle Aged, Retrospective Studies
Abstract

To assess the disease burden and health economics of inpatients with multiple sclerosis (MS) in China by evaluating the direct, indirect, and intangible costs.A total of 863 patients were included for a cross-sectional retrospective study in 50 centers. The direct economic burden was measured by the cost of hospitalization and out-of-hospital application drugs, and the indirect economic burden was measured by the human capital method. The disability-adjusted life year (DALY) was used to express the intangible economic burden. Cost-utility analysis (CUA) using DALYs as indicators of health benefits was performed by calculating the incremental cost-utility ratio.The mean direct economic burden/year, daily medication expenses/year, DALY, indirect economic burden, and indirect economic burden/year were 27,655.57 Yuan, 17,944.97 Yuan, 10.89 Yuan, 512,041.7 Yuan, and 11,299.85 Yuan, respectively. For the study period of two years, the direct economic burden, daily medication expense, and indirect economic burden were 48.6%, 31.5%, and 19.85% of the total economic burden, respectively. Disease burden and the number of episodes of remission were not statistically significant (p0.001). The direct economic burden and total economic burden of the disease-modifying therapy (DMT) group were higher than those of the non-DMT group, but DALYs had no statistical significance (p0.001). CUA showed that inpatients with MS in the DMT group received a DALY every time compared with the non-DMT group.The DALY losses are concentrated in young and middle-aged Chinese people. In this two-year study, CUA prompted the application of DMT drugs to increase the economic burden and DALYs. However, follow-up time is still short, and further follow-up observation is required.

Published
2022
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18. Status of Immunotherapy Acceptance in Chinese Patients With Multiple Sclerosis: Analysis of Multiple Sclerosis Patient Survival Report 2018

Author

Zhou, Ran, primary, Zeng, Qiuming, additional, Yang, Huan, additional, Xu, Yan, additional, Tan, Guojun, additional, Liu, Hongbo, additional, Wang, Lihua, additional, Zhou, Hongyu, additional, Zhang, Meini, additional, Feng, Jinzhou, additional, Jin, Tao, additional, Zhang, Xinghu, additional, Wang, Jiawei, additional, Zhang, Xu, additional, Gao, Feng, additional, Yang, Chunsheng, additional, Bu, Bitao, additional, Li, Chunyang, additional, Zhang, Min, additional, Dong, Huiqing, additional, Lin, Aiyu, additional, Liu, Weibin, additional, Wu, Lei, additional, Wang, Manxia, additional, Tang, Yulan, additional, Wang, Honghao, additional, Long, Youming, additional, Wang, Zhe, additional, and Zheng, Weihong, additional

Published
2021
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21. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study

Author

Kappos, Ludwig, primary, Bar-Or, Amit, additional, Cree, Bruce A C, additional, Fox, Robert J, additional, Giovannoni, Gavin, additional, Gold, Ralf, additional, Vermersch, Patrick, additional, Arnold, Douglas L, additional, Arnould, Sophie, additional, Scherz, Tatiana, additional, Wolf, Christian, additional, Wallström, Erik, additional, Dahlke, Frank, additional, Achiron, Anat, additional, Achtnichts, Lutz, additional, Agan, Kadriye, additional, Akman-Demir, Gulsen, additional, Allen, Alison B, additional, Antel, Jack P, additional, Antiguedad, Alfredo Rodriguez, additional, Apperson, Michelle, additional, Applebee, Angela M, additional, Ayuso, Guillermo Izquierdo, additional, Baba, Masayuki, additional, Bajenaru, Ovidiu, additional, Balasa, Rodica, additional, Balci, Belgin Petek, additional, Barnett, Michael, additional, Bass, Ann, additional, Becker, Veit U, additional, Bejinariu, Mihaela, additional, Bergh, Florian Then, additional, Bergmann, Arnfin, additional, Bernitsas, Evanthia, additional, Berthele, Achim, additional, Bhan, Virender, additional, Bischof, Felix, additional, Bjork, Randall John, additional, Blevins, Gregg, additional, Boehringer, Matthias, additional, Boerner, Thomas, additional, Bonek, Robert, additional, Bowen, James D, additional, Bowling, Allen, additional, Boyko, Alexey N, additional, Boz, Cavit, additional, Bracknies, Vera, additional, Braune, Stefan, additional, Brescia Morra, Vincenzo, additional, Brochet, Bruno, additional, Brola, Waldemar, additional, Brownstone, Paul Kenneth, additional, Brozman, Miroslav, additional, Brunet, Donald, additional, Buraga, Ioan, additional, Burnett, Margaret, additional, Buttmann, Mathias, additional, Butzkueven, Helmut, additional, Cahill, Jonathan, additional, Calkwood, Jonathan C, additional, Camu, William, additional, Cascione, Mark, additional, Castelnovo, Giovani, additional, Centonze, Diego, additional, Cerqueira, Joao, additional, Chan, Andrew, additional, Cimprichova, Andrea, additional, Cohan, Stanley, additional, Comi, Giancarlo, additional, Conway, Jill, additional, Cooper, Joanna A, additional, Corboy, John, additional, Correale, Jorge, additional, Costell, Brian, additional, Cottrell, David A, additional, Coyle, Patricia K, additional, Craner, Matthew, additional, Cui, Liying, additional, Cunha, Luis, additional, Czlonkowska, Anna, additional, da Silva, Ana Martins, additional, de Sa, Joao, additional, de Seze, Jérôme, additional, Debouverie, Marc, additional, Debruyne, Jan, additional, Decoo, Danny, additional, Defer, Gilles, additional, Derfuss, Tobias, additional, Deri, Norma H, additional, Dihenia, Bhupesh, additional, Dioszeghy, Peter, additional, Donath, Vladimir, additional, Dubois, Benedicte, additional, Duddy, Martin, additional, Duquette, Pierre, additional, Edan, Gilles, additional, Efendi, Husnu, additional, Elias, Stanton, additional, Emrich, Peter J, additional, Estruch, Bonaventura Casanova, additional, Evdoshenko, Evgeniy P, additional, Faiss, Juergen, additional, Fedyanin, Alexander S, additional, Feneberg, Wolfgang, additional, Fermont, Jiske, additional, Fernandez, Oscar Fernandez, additional, Ferrer, Francisco Coret, additional, Fink, Katharina, additional, Ford, Helen, additional, Ford, Corey, additional, Francia, Ada, additional, Freedman, Mark, additional, Frishberg, Benjamin, additional, Galgani, Simonetta, additional, Garmany, George P, additional, Gehring, Klaus, additional, Gitt, Jeffrey, additional, Gobbi, Claudio, additional, Goldstick, Lawrence P, additional, Gonzalez, Rafael Arroyo, additional, Grandmaison, Francois, additional, Grigoriadis, Nikolaos, additional, Grigorova, Olga, additional, Grimaldi, Luigi Maria Edoardo, additional, Gross, Jeffrey, additional, Gross-Paju, Katrin, additional, Gudesblatt, Mark, additional, Guillaume, Daniel, additional, Haas, Judith, additional, Hancinova, Viera, additional, Hancu, Anca, additional, Hardiman, Orla, additional, Harmjanz, Arndt, additional, Heidenreich, Fedor R, additional, Hengstman, G J D, additional, Herbert, Joseph, additional, Herring, Mark, additional, Hodgkinson, Suzanne, additional, Hoffmann, Olaf M, additional, Hofmann, Werner E, additional, Honeycutt, William D, additional, Hua, Le Hanh, additional, Huang, Dehui, additional, Huang, Yining, additional, Huang, DeRen, additional, Hupperts, Raymond, additional, Imre, Piroska, additional, Jacobs, Alan Keith, additional, Jakab, Gabor, additional, Jasinska, Elzbieta, additional, Kaida, Kenichi, additional, Kalnina, Jolanta, additional, Kaprelyan, Ara, additional, Karelis, Guntis, additional, Karussis, Dimitrios, additional, Katz, Amos, additional, Khabirov, Farit A, additional, Khatri, Bhupendra, additional, Kimura, Takashi, additional, Kister, Ilya, additional, Kizlaitiene, Rasa, additional, Klimova, Eleonora, additional, Koehler, Juergen, additional, Komatineni, Aparna, additional, Kornhuber, Anselm, additional, Kovacs, Krisztina, additional, Koves, Agnes, additional, Kozubski, Wojciech, additional, Krastev, Georgi, additional, Krupp, Lauren B, additional, Kurca, Egon, additional, Lassek, Christoph, additional, Laureys, Guy, additional, Lee, Liesly, additional, Lensch, Eckart, additional, Leutmezer, Fritz, additional, Li, Hongzeng, additional, Linker, Ralf A, additional, Linnebank, Michael, additional, Liskova, Petra, additional, Llanera, Cristina, additional, Lu, Jiahong, additional, Lutterotti, Andreas, additional, Lycke, Jan, additional, Macdonell, Richard, additional, Maciejowski, Maciej, additional, Maeurer, Mathias, additional, Magzhanov, Rim V, additional, Maida, Eva-Maria, additional, Malciene, Lina, additional, Mao-Draayer, Yang, additional, Marfia, Girolama Alessandra, additional, Markowitz, Clyde, additional, Mastorodimos, Vasileios, additional, Matyas, Klotild, additional, Meca-Lallana, Jose, additional, Merino, Juan Antonio Garcia, additional, Mihetiu, Ioan Gheorghe, additional, Milanov, Ivan, additional, Miller, Aaron E, additional, Millers, Andrejs, additional, Mirabella, Massimiliano, additional, Mizuno, Masanori, additional, Montalban, Xavier, additional, Montoya, Lilina, additional, Mori, Masahiro, additional, Mueller, Stefanie, additional, Nakahara, Jin, additional, Nakatsuji, Yuji, additional, Newsome, Scott, additional, Nicholas, Richard, additional, Nielsen, A Scott, additional, Nikfekr, Esmaeil, additional, Nocentini, Ugo, additional, Nohara, Chiyoko, additional, Nomura, Kyoichi, additional, Odinak, Miroslav M, additional, Olsson, Tomas, additional, van Oosten, B W, additional, Oreja-Guevara, Celia, additional, Oschmann, Patrick, additional, Overell, James, additional, Pachner, Andrew, additional, Panczel, Gyula, additional, Pandolfo, Massimo, additional, Papeix, Caroline, additional, Patrucco, Liliana, additional, Pelletier, Jean, additional, Piedrabuena, Raul, additional, Pless, Misha, additional, Polzer, Udo, additional, Pozsegovits, Krisztian, additional, Rastenyte, Daiva, additional, Rauer, Sebastian, additional, Reifschneider, Gerd, additional, Rey, Roberto, additional, Rizvi, Syed A, additional, Robertson, Derrick, additional, Rodriguez, Jose Martinez, additional, Rog, David, additional, Roshanisefat, Homayoun, additional, Rowe, Vernon, additional, Rozsa, Csilla, additional, Rubin, Susan, additional, Rusek, Stanislaw, additional, Saccà, Francesco, additional, Saida, Takahiko, additional, Salgado, Antonio Vasco, additional, Sanchez, Victoria Eugenia Fernandez, additional, Sanders, Kalina, additional, Satori, Maria, additional, Sazonov, Denis V, additional, Scarpini, Elio Angelo, additional, Schlegel, Eugen, additional, Schluep, Myriam, additional, Schmidt, Stephan, additional, Scholz, Erich, additional, Schrijver, H M, additional, Schwab, Matthias, additional, Schwartz, Raymond, additional, Scott, James, additional, Selmaj, Krzysztof, additional, Shafer, Stuart, additional, Sharrack, Basil, additional, Shchukin, Ivan A, additional, Shimizu, Yuko, additional, Shotekov, Penko, additional, Siever, Arno, additional, Sigel, Karl-Otto, additional, Silliman, Scott, additional, Simo, Magdolna, additional, Simu, Mihaela, additional, Sinay, Vladimiro, additional, Siquier, Antonio Escartin, additional, Siva, Aksel, additional, Skoda, Ondrej, additional, Solomon, Andrew, additional, Stangel, Martin, additional, Stefoski, Dusan, additional, Steingo, Brian, additional, Stolyarov, Igor D, additional, Stourac, Pavel, additional, Strassburger-Krogias, Katrin, additional, Strauss, Erik, additional, Stuve, Olaf, additional, Tarnev, Ivaylo, additional, Tavernarakis, Antonios, additional, Tello, Cristina Ramo, additional, Terzi, Murat, additional, Ticha, Veronika, additional, Ticmeanu, Marina, additional, Tiel-Wilck, Klaus, additional, Toomsoo, Toomas, additional, Tubridy, Niall, additional, Tullman, Mark J, additional, Tumani, Hayrettin, additional, Turcani, Peter, additional, Turner, Ben, additional, Uccelli, Antonio, additional, Urtaza, Francisco Javier Olascoaga, additional, Vachova, Marta, additional, Valikovics, Attila, additional, Walter, Silke, additional, Van Wijmeersch, Bart, additional, Vanopdenbosch, Ludo, additional, Weber, Joerg R, additional, Weiss, Sara, additional, Weissert, Robert, additional, West, Timothy, additional, Wiendl, Heinz, additional, Wiertlewski, Sandrine, additional, Wildemann, Brigitte, additional, Willekens, Barbara, additional, Visser, L H, additional, Vorobeychik, Galina, additional, Xu, Xianhao, additional, Yamamura, Takashi, additional, Yang, Yi N, additional, Yelamos, Sergio Martinez, additional, Yeung, Michael, additional, Zacharias, Alan, additional, Zelkowitz, Marvin, additional, Zettl, Uwe, additional, Zhang, Meini, additional, Zhou, Hongyu, additional, Zieman, Ulf, additional, and Ziemssen, Tjalf, additional

Published
2018
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22. Athenoxat-1, Night Vision Experiments in LEO

Author

Manzoni, Giulio, Brama, Yesie L., and Zhang, Meini

Abstract

On 16th December 2015 Athenoxat-1 was launched by a PSLV from India in to Equatorial Orbit. Athenoxat-1 has been developed by Microspace Rapid Pte Ltd to demonstrate the feasibility of night vision imaging on a 3U Cubesat. The night vision payload is based on a high sensitive CCD and, in combination with the large optical aperture allows for very fast imaging of Earth surface in the night with 25m resolution. In addition to the main payload, Athenoxat-1 is equipped with 4 optical payloads for wide angle and horizon imaging. Sensor placement allows capturing a synchronized view of Earth and Space across almost 4Pi steradians thereby allowing various ADCS experiments such as Nadir determination and Moon tracking. Attitude control is achieved by magnetorquers and reaction wheels specifically developed for this mission. The talk will focus on the mission achievements, difficulties and challenges and, while discussing the lessons learned, will trace a roadmap for future work.

Published
2016

25. High-Temperature Dielectric Relaxation in Pb( Mg1/3 Nb2/3) O3- PbTiO3 Single Crystals.

Author

Wang, Chunchang, Zhang, Meini, Xia, Wei, and Tan, X.

Subjects
*OXYGEN, *ELECTRODES, *DIELECTRIC properties, *CRYSTALS, *FERROELECTRIC crystals
Abstract

We reported the dielectric properties of Pb( Mg1/3 Nb2/3) O3- PbTiO3 single crystal in the temperature range of 300-1073 K and the frequency range of 100 Hz-10 MHz. Our results showed the coexistence of both true- and pseudo-relaxor behaviors in the crystal. The true relaxor behavior related to the paraelectric-ferroelectric phase transition occurs at~423 K. The pseudo-relaxor behavior appearing at~773 K was found to be related to oxygen vacancies. Further investigation reveals that the pseudo-relaxor behavior has fine structure: it contains two oxygen-vacancy-related relaxation processes. The low-temperature relaxation process is a dipolar relaxation created by the hopping motions of the oxygen vacancies, and the high-temperature relaxation process is a Maxwell-Wagner relaxation caused by the sample/electrode contacts. [ABSTRACT FROM AUTHOR]

Published
2013
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26. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study

Author

Ludwig Kappos, Amit Bar-Or, Bruce A C Cree, Robert J Fox, Gavin Giovannoni, Ralf Gold, Patrick Vermersch, Douglas L Arnold, Sophie Arnould, Tatiana Scherz, Christian Wolf, Erik Wallström, Frank Dahlke, Anat Achiron, Lutz Achtnichts, Kadriye Agan, Gulsen Akman-Demir, Alison B Allen, Jack P Antel, Alfredo Rodriguez Antiguedad, Michelle Apperson, Angela M Applebee, Guillermo Izquierdo Ayuso, Masayuki Baba, Ovidiu Bajenaru, Rodica Balasa, Belgin Petek Balci, Michael Barnett, Ann Bass, Veit U Becker, Mihaela Bejinariu, Florian Then Bergh, Arnfin Bergmann, Evanthia Bernitsas, Achim Berthele, Virender Bhan, Felix Bischof, Randall John Bjork, Gregg Blevins, Matthias Boehringer, Thomas Boerner, Robert Bonek, James D Bowen, Allen Bowling, Alexey N Boyko, Cavit Boz, Vera Bracknies, Stefan Braune, Vincenzo Brescia Morra, Bruno Brochet, Waldemar Brola, Paul Kenneth Brownstone, Miroslav Brozman, Donald Brunet, Ioan Buraga, Margaret Burnett, Mathias Buttmann, Helmut Butzkueven, Jonathan Cahill, Jonathan C Calkwood, William Camu, Mark Cascione, Giovani Castelnovo, Diego Centonze, Joao Cerqueira, Andrew Chan, Andrea Cimprichova, Stanley Cohan, Giancarlo Comi, Jill Conway, Joanna A Cooper, John Corboy, Jorge Correale, Brian Costell, David A Cottrell, Patricia K Coyle, Matthew Craner, Liying Cui, Luis Cunha, Anna Czlonkowska, Ana Martins da Silva, Joao de Sa, Jérôme de Seze, Marc Debouverie, Jan Debruyne, Danny Decoo, Gilles Defer, Tobias Derfuss, Norma H Deri, Bhupesh Dihenia, Peter Dioszeghy, Vladimir Donath, Benedicte Dubois, Martin Duddy, Pierre Duquette, Gilles Edan, Husnu Efendi, Stanton Elias, Peter J Emrich, Bonaventura Casanova Estruch, Evgeniy P Evdoshenko, Juergen Faiss, Alexander S Fedyanin, Wolfgang Feneberg, Jiske Fermont, Oscar Fernandez Fernandez, Francisco Coret Ferrer, Katharina Fink, Helen Ford, Corey Ford, Ada Francia, Mark Freedman, Benjamin Frishberg, Simonetta Galgani, George P Garmany, Klaus Gehring, Jeffrey Gitt, Claudio Gobbi, Lawrence P Goldstick, Rafael Arroyo Gonzalez, Francois Grandmaison, Nikolaos Grigoriadis, Olga Grigorova, Luigi Maria Edoardo Grimaldi, Jeffrey Gross, Katrin Gross-Paju, Mark Gudesblatt, Daniel Guillaume, Judith Haas, Viera Hancinova, Anca Hancu, Orla Hardiman, Arndt Harmjanz, Fedor R Heidenreich, G J D Hengstman, Joseph Herbert, Mark Herring, Suzanne Hodgkinson, Olaf M Hoffmann, Werner E Hofmann, William D Honeycutt, Le Hanh Hua, Dehui Huang, Yining Huang, DeRen Huang, Raymond Hupperts, Piroska Imre, Alan Keith Jacobs, Gabor Jakab, Elzbieta Jasinska, Kenichi Kaida, Jolanta Kalnina, Ara Kaprelyan, Guntis Karelis, Dimitrios Karussis, Amos Katz, Farit A Khabirov, Bhupendra Khatri, Takashi Kimura, Ilya Kister, Rasa Kizlaitiene, Eleonora Klimova, Juergen Koehler, Aparna Komatineni, Anselm Kornhuber, Krisztina Kovacs, Agnes Koves, Wojciech Kozubski, Georgi Krastev, Lauren B Krupp, Egon Kurca, Christoph Lassek, Guy Laureys, Liesly Lee, Eckart Lensch, Fritz Leutmezer, Hongzeng Li, Ralf A Linker, Michael Linnebank, Petra Liskova, Cristina Llanera, Jiahong Lu, Andreas Lutterotti, Jan Lycke, Richard Macdonell, Maciej Maciejowski, Mathias Maeurer, Rim V Magzhanov, Eva-Maria Maida, Lina Malciene, Yang Mao-Draayer, Girolama Alessandra Marfia, Clyde Markowitz, Vasileios Mastorodimos, Klotild Matyas, Jose Meca-Lallana, Juan Antonio Garcia Merino, Ioan Gheorghe Mihetiu, Ivan Milanov, Aaron E Miller, Andrejs Millers, Massimiliano Mirabella, Masanori Mizuno, Xavier Montalban, Lilina Montoya, Masahiro Mori, Stefanie Mueller, Jin Nakahara, Yuji Nakatsuji, Scott Newsome, Richard Nicholas, A Scott Nielsen, Esmaeil Nikfekr, Ugo Nocentini, Chiyoko Nohara, Kyoichi Nomura, Miroslav M Odinak, Tomas Olsson, B W van Oosten, Celia Oreja-Guevara, Patrick Oschmann, James Overell, Andrew Pachner, Gyula Panczel, Massimo Pandolfo, Caroline Papeix, Liliana Patrucco, Jean Pelletier, Raul Piedrabuena, Misha Pless, Udo Polzer, Krisztian Pozsegovits, Daiva Rastenyte, Sebastian Rauer, Gerd Reifschneider, Roberto Rey, Syed A Rizvi, Derrick Robertson, Jose Martinez Rodriguez, David Rog, Homayoun Roshanisefat, Vernon Rowe, Csilla Rozsa, Susan Rubin, Stanislaw Rusek, Francesco Saccà, Takahiko Saida, Antonio Vasco Salgado, Victoria Eugenia Fernandez Sanchez, Kalina Sanders, Maria Satori, Denis V Sazonov, Elio Angelo Scarpini, Eugen Schlegel, Myriam Schluep, Stephan Schmidt, Erich Scholz, H M Schrijver, Matthias Schwab, Raymond Schwartz, James Scott, Krzysztof Selmaj, Stuart Shafer, Basil Sharrack, Ivan A Shchukin, Yuko Shimizu, Penko Shotekov, Arno Siever, Karl-Otto Sigel, Scott Silliman, Magdolna Simo, Mihaela Simu, Vladimiro Sinay, Antonio Escartin Siquier, Aksel Siva, Ondrej Skoda, Andrew Solomon, Martin Stangel, Dusan Stefoski, Brian Steingo, Igor D Stolyarov, Pavel Stourac, Katrin Strassburger-Krogias, Erik Strauss, Olaf Stuve, Ivaylo Tarnev, Antonios Tavernarakis, Cristina Ramo Tello, Murat Terzi, Veronika Ticha, Marina Ticmeanu, Klaus Tiel-Wilck, Toomas Toomsoo, Niall Tubridy, Mark J Tullman, Hayrettin Tumani, Peter Turcani, Ben Turner, Antonio Uccelli, Francisco Javier Olascoaga Urtaza, Marta Vachova, Attila Valikovics, Silke Walter, Bart Van Wijmeersch, Ludo Vanopdenbosch, Joerg R Weber, Sara Weiss, Robert Weissert, Timothy West, Heinz Wiendl, Sandrine Wiertlewski, Brigitte Wildemann, Barbara Willekens, L H Visser, Galina Vorobeychik, Xianhao Xu, Takashi Yamamura, Yi N Yang, Sergio Martinez Yelamos, Michael Yeung, Alan Zacharias, Marvin Zelkowitz, Uwe Zettl, Meini Zhang, Hongyu Zhou, Ulf Zieman, Tjalf Ziemssen, Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital, University of Basel, Basel, Center for Neuroinflammation and Neurotherapeutics, and Multiple Sclerosis Division, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, Neuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, UCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, Mellen Centre for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, Department of Neurology St. Josef-Hospital, Ruhr University Bochum, Germany, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Montreal Neurological Institute, McGill University, Montreal, QC, Canada, NeuroRx Research, Montreal, QC, Novartis Pharma AG, Lycalis, Brussels, AP-HM, CHU Timone, Pole de Neurosciences Cliniques, Department of Neurology, Marseille, France., 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), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-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)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Kappos, Ludwig, Bar-Or, Amit, Cree, Bruce A C, Fox, Robert J, Giovannoni, Gavin, Gold, Ralf, Vermersch, Patrick, Arnold, Douglas L, Arnould, Sophie, Scherz, Tatiana, Wolf, Christian, Wallström, Erik, Dahlke, Frank, Achiron, Anat, Achtnichts, Lutz, Agan, Kadriye, Akman-Demir, Gulsen, Allen, Alison B, Antel, Jack P, Antiguedad, Alfredo Rodriguez, Apperson, Michelle, Applebee, Angela M, Ayuso, Guillermo Izquierdo, Baba, Masayuki, Bajenaru, Ovidiu, Balasa, Rodica, Balci, Belgin Petek, Barnett, Michael, Bass, Ann, Becker, Veit U, Bejinariu, Mihaela, Bergh, Florian Then, Bergmann, Arnfin, Bernitsas, Evanthia, Berthele, Achim, Bhan, Virender, Bischof, Felix, Bjork, Randall John, Blevins, Gregg, Boehringer, Matthia, Boerner, Thoma, Bonek, Robert, Bowen, James D, Bowling, Allen, Boyko, Alexey N, Boz, Cavit, Bracknies, Vera, Braune, Stefan, Brescia Morra, Vincenzo, Brochet, Bruno, Brola, Waldemar, Brownstone, Paul Kenneth, Brozman, Miroslav, Brunet, Donald, Buraga, Ioan, Burnett, Margaret, Buttmann, Mathia, Butzkueven, Helmut, Cahill, Jonathan, Calkwood, Jonathan C, Camu, William, Cascione, Mark, Castelnovo, Giovani, Centonze, Diego, Cerqueira, Joao, Chan, Andrew, Cimprichova, Andrea, Cohan, Stanley, Comi, Giancarlo, Conway, Jill, Cooper, Joanna A, Corboy, John, Correale, Jorge, Costell, Brian, Cottrell, David A, Coyle, Patricia K, Craner, Matthew, Cui, Liying, Cunha, Lui, Czlonkowska, Anna, da Silva, Ana Martin, de Sa, Joao, de Seze, Jérôme, Debouverie, Marc, Debruyne, Jan, Decoo, Danny, Defer, Gille, Derfuss, Tobia, Deri, Norma H, Dihenia, Bhupesh, Dioszeghy, Peter, Donath, Vladimir, Dubois, Benedicte, Duddy, Martin, Duquette, Pierre, Edan, Gille, Efendi, Husnu, Elias, Stanton, Emrich, Peter J, Estruch, Bonaventura Casanova, Evdoshenko, Evgeniy P, Faiss, Juergen, Fedyanin, Alexander S, Feneberg, Wolfgang, Fermont, Jiske, Fernandez, Oscar Fernandez, Ferrer, Francisco Coret, Fink, Katharina, Ford, Helen, Ford, Corey, Francia, Ada, Freedman, Mark, Frishberg, Benjamin, Galgani, Simonetta, Garmany, George P, Gehring, Klau, Gitt, Jeffrey, Gobbi, Claudio, Goldstick, Lawrence P, Gonzalez, Rafael Arroyo, Grandmaison, Francoi, Grigoriadis, Nikolao, Grigorova, Olga, Grimaldi, Luigi Maria Edoardo, Gross, Jeffrey, Gross-Paju, Katrin, Gudesblatt, Mark, Guillaume, Daniel, Haas, Judith, Hancinova, Viera, Hancu, Anca, Hardiman, Orla, Harmjanz, Arndt, Heidenreich, Fedor R, Hengstman, G J D, Herbert, Joseph, Herring, Mark, Hodgkinson, Suzanne, Hoffmann, Olaf M, Hofmann, Werner E, Honeycutt, William D, Hua, Le Hanh, Huang, Dehui, Huang, Yining, Huang, Deren, Hupperts, Raymond, Imre, Piroska, Jacobs, Alan Keith, Jakab, Gabor, Jasinska, Elzbieta, Kaida, Kenichi, Kalnina, Jolanta, Kaprelyan, Ara, Karelis, Gunti, Karussis, Dimitrio, Katz, Amo, Khabirov, Farit A, Khatri, Bhupendra, Kimura, Takashi, Kister, Ilya, Kizlaitiene, Rasa, Klimova, Eleonora, Koehler, Juergen, Komatineni, Aparna, Kornhuber, Anselm, Kovacs, Krisztina, Koves, Agne, Kozubski, Wojciech, Krastev, Georgi, Krupp, Lauren B, Kurca, Egon, Lassek, Christoph, Laureys, Guy, Lee, Liesly, Lensch, Eckart, Leutmezer, Fritz, Li, Hongzeng, Linker, Ralf A, Linnebank, Michael, Liskova, Petra, Llanera, Cristina, Lu, Jiahong, Lutterotti, Andrea, Lycke, Jan, Macdonell, Richard, Maciejowski, Maciej, Maeurer, Mathia, Magzhanov, Rim V, Maida, Eva-Maria, Malciene, Lina, Mao-Draayer, Yang, Marfia, Girolama Alessandra, Markowitz, Clyde, Mastorodimos, Vasileio, Matyas, Klotild, Meca-Lallana, Jose, Merino, Juan Antonio Garcia, Mihetiu, Ioan Gheorghe, Milanov, Ivan, Miller, Aaron E, Millers, Andrej, Mirabella, Massimiliano, Mizuno, Masanori, Montalban, Xavier, Montoya, Lilina, Mori, Masahiro, Mueller, Stefanie, Nakahara, Jin, Nakatsuji, Yuji, Newsome, Scott, Nicholas, Richard, Nielsen, A Scott, Nikfekr, Esmaeil, Nocentini, Ugo, Nohara, Chiyoko, Nomura, Kyoichi, Odinak, Miroslav M, Olsson, Toma, van Oosten, B W, Oreja-Guevara, Celia, Oschmann, Patrick, Overell, Jame, Pachner, Andrew, Panczel, Gyula, Pandolfo, Massimo, Papeix, Caroline, Patrucco, Liliana, Pelletier, Jean, Piedrabuena, Raul, Pless, Misha, Polzer, Udo, Pozsegovits, Krisztian, Rastenyte, Daiva, Rauer, Sebastian, Reifschneider, Gerd, Rey, Roberto, Rizvi, Syed A, Robertson, Derrick, Rodriguez, Jose Martinez, Rog, David, Roshanisefat, Homayoun, Rowe, Vernon, Rozsa, Csilla, Rubin, Susan, Rusek, Stanislaw, Saccà, Francesco, Saida, Takahiko, Salgado, Antonio Vasco, Sanchez, Victoria Eugenia Fernandez, Sanders, Kalina, Satori, Maria, Sazonov, Denis V, Scarpini, Elio Angelo, Schlegel, Eugen, Schluep, Myriam, Schmidt, Stephan, Scholz, Erich, Schrijver, H M, Schwab, Matthia, Schwartz, Raymond, Scott, Jame, Selmaj, Krzysztof, Shafer, Stuart, Sharrack, Basil, Shchukin, Ivan A, Shimizu, Yuko, Shotekov, Penko, Siever, Arno, Sigel, Karl-Otto, Silliman, Scott, Simo, Magdolna, Simu, Mihaela, Sinay, Vladimiro, Siquier, Antonio Escartin, Siva, Aksel, Skoda, Ondrej, Solomon, Andrew, Stangel, Martin, Stefoski, Dusan, Steingo, Brian, Stolyarov, Igor D, Stourac, Pavel, Strassburger-Krogias, Katrin, Strauss, Erik, Stuve, Olaf, Tarnev, Ivaylo, Tavernarakis, Antonio, Tello, Cristina Ramo, Terzi, Murat, Ticha, Veronika, Ticmeanu, Marina, Tiel-Wilck, Klau, Toomsoo, Tooma, Tubridy, Niall, Tullman, Mark J, Tumani, Hayrettin, Turcani, Peter, Turner, Ben, Uccelli, Antonio, Urtaza, Francisco Javier Olascoaga, Vachova, Marta, Valikovics, Attila, Walter, Silke, Van Wijmeersch, Bart, Vanopdenbosch, Ludo, Weber, Joerg R, Weiss, Sara, Weissert, Robert, West, Timothy, Wiendl, Heinz, Wiertlewski, Sandrine, Wildemann, Brigitte, Willekens, Barbara, Visser, L H, Vorobeychik, Galina, Xu, Xianhao, Yamamura, Takashi, Yang, Yi N, Yelamos, Sergio Martinez, Yeung, Michael, Zacharias, Alan, Zelkowitz, Marvin, Zettl, Uwe, Zhang, Meini, Zhou, Hongyu, Zieman, Ulf, Ziemssen, Tjalf, and EXPAND Clinical Investigators

Subjects
Adult, Male, 0301 basic medicine, Relative risk reduction, medicine.medical_specialty, Adolescent, Placebo, law.invention, Cohort Studies, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, Multiple Sclerosis, Chronic Progressive / drug therapy, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Internal medicine, Benzyl Compounds, Clinical endpoint, Humans, Medicine, ComputingMilieux_MISCELLANEOUS, Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA, Expanded Disability Status Scale, Dose-Response Relationship, Drug, business.industry, Hazard ratio, General Medicine, Middle Aged, Multiple Sclerosis, Chronic Progressive, Fingolimod, Treatment Outcome, Settore M-EDF/01 - METODI E DIDATTICHE DELLE ATTIVITÀ MOTORIE, 030104 developmental biology, Siponimod, chemistry, Disease Progression, Azetidines, Female, Settore MED/26 - Neurologia, Human medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, medicine.drug
Abstract

Summary Background No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding Novartis Pharma AG.

Published
2018
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