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2. Safety and efficacy of evobrutinib in relapsing multiple sclerosis (evolutionRMS1 and evolutionRMS2): two multicentre, randomised, double-blind, active-controlled, phase 3 trials

Author

Carra, Adriana Josefa, Deri, Norma Haydee, Jose, Jorge Gustavo, del Valle Liwacki, Susana, Mainella, Carolina Natalia, Pagani, Fatima, Povedano, Guillermo, Alfici, Alberto Rodriguez, Tavolini, Dario Raul, Buonanotte, Carlos Federico, Burgos, Marcos, Giugni, Juan Carlos, Artesi, Juan Jose Martin, Rojas, Juan Ignacio, Zuin, Daniel Raul, Videla, Hugo Osvaldo, Correale, Jorge Daniel, Luetic, Geraldine G., Hodgkinson, Suzanne, Lechner-Scott, Jeannette, Parratt, John, Saines, Noel, Reddel, Stephen, Wijeratne, Tissa, Taylor, Bruce, Deisenhammer, Florian, Traxler, Gerhard, Leutmezer, Fritz, Wipfler, Peter, Weber, Joerg R., Lampl, Christian, Bartholome, Emmanuel, Dive, Dominique, Glibert, Nele, Perrotta, Gaetano, Pesch, Vincent, Buyle, Maarten, Wijmeersch, Bart, Willekens, Barbara, Basagic, Edin, Mehmedika Suljic, Enra, Klupka-Sarić, Inge, Danovska, Maya, Dimitrova, Maria, Genov, Krasimir, Izmaylov, Alim, Mavrov, Radoslav, Milanov, Ivan, Naydenov, Valcho, Shotekov, Penko, Tarnev, Ivaylo, Traykov, Latchezar, Emond, Francois, Selchen, Daniel, Rivest, Donald, Sabella, Lisa, Witkowski, Ludivine, Saveriano, Alexander, Bolano Solano, Addinson Rene, Ruiz, Cesar Augusto Franco, Nassar Tobon, Andrea Catalina, Cardozo, Carlos Alberto Navas, Schlesenger, Antonio, Triana, Javier Dario, Sarabia, Osvaldo Elias Lara, Montero, Luis Alfonso Zarco, Arango, Jorge Andres Jimenez, Basic, Silvio, Pasic, Marija Bosnjak, Soldo, Silva Butkovic, Habek, Mario, Kidjemet-Piskac, Spomenka, Matijaca, Meri, Vuletic, Vladimira, Ampapa, Radek, Dufek, Michal, Grunermelova, Marketa, Mares, Jan, Martinkova, Alena, Peterka, Marek, Stetkarova, Ivana, Stourac, Pavel, Talab, Radomir, Tyblova, Michaela, Marta, Vachova, Valis, Martin, Hradilek, Pavel, Rockova, Petra, Gross-Paju, Katrin, Haldre, Sulev, Airas, Laura, Karppa, Mikko, Bourre, Bertrand, Casez, Olivier, Ciron, Jonathan, Kwitakowski, Arnaud, Labauge, Pierre, Lebrun Frenay, Christine, Michel, Laure, Derache, Nathalie, Vukusic, Sandra, Laplaud, David-Axel, Beridze, Maia, Chakhava, George, Gauarashvili, Ann, Giorgadze, Gvantsa, Guldedava, Nana, Janelidze, Marina, Kiziria, Marina, Shakarishvili, Roman, Tsiskaridze, Alexander, Chkhikvishvili, Shalva, Albert, Christian, Berthele, Achim, Yalachkov, Yavor, Pitarokoili, Kalliopi, Kallmann, Boris-Alexander, Klotz, Luisa, Oschmann, Patrick, Pul, Refik, Rau, Daniela, Skripuletz, Thomas, Chan, Koon Ho, Lau, Alexander Yuk Lun, Li, Jessica Tsz Ching, Wong, Wa Tai, Maria, Biro Zita, Bokor, Magdolna, Dobos, Eniko, Janszky, Jozsef, Kovacs, Krisztina, Lazarcsik, Ildiko, Piros, Palma, Rozsa, Csilla, Satori, Maria, Simo, Magdolna, Nagy, Ferenc, Behari, Madhuri, Kulkarni, Rahul, Kumar, Radhakrishanan Suresh, Dwivedee, Shamsher, Iype, Thomas, Baviskar, Rahul, Mathukumalli, Neeharika L., Gilad, Ronit, Karussis, Dimitrios, Milo, Ron, Shahien, Radi, Vaknin, Adi, Weller, Boaz, Wilf-Yarkoni, Adi, Achiron, Anat, Aguglia, Umberto, Di Gregorio, Maria, Calabrese, Massimiliano, Cordioli, Cinzia, Sessa, Edoardo, Tomassini, Valentina, Inglese, Matilde, Castro Farfan, Freddy Guillermo, Roldan, Giovana Femat, Gonzalez Guardado, Antonio, Lopez Meza, Elmer, Maldonado, Jair Fernando, Boschetti, Laura Ordonez, Partida Medina, Luis Roberto, Frequin, Stephan, Hupperts, Raymond, Schrijver, Hans, Smolders, Joost, Diaz, Cesar Abel Castaneda, Pretell, Edwin, Boczarska-Jedynak, Magdalena, Bonek, Robert, Brola, Waldemar, Darda-Ledzion, Lidia, Fryze, Waldemar, Maciejowski, Maciej, Rejdak, Konrad, Rosciszewska-Zukowska, Iwona, Selmaj, Krzysztof, Szymanska, Malgorzata, Zajda, Małgorzata, Zielinski, Tomasz, Beata, Zakrzewska-Pniewska, Adam, Stepien, Swiat, Maciej, Kim, Byoung Joon, Kim, Ho-Jin, Kim, Kwang-Kuk, Shin, Ha Young, Kim, Sung Min, Kim, Woojun, Oh, Jeeyoung, Bakhtiyarova, Klara Z., Belova, Anna N., Davydovskaya, Maria V., Dudin, Viacheslav A., Erina, Olesya V., Evdoshenko, Evgeny P., Greshnova, Irina V., Khabirov, Farit A., Kotov, Sergey V., Makarov, Nikolay S., Maslova, Natalia, Mishin, Gennadiy N., Pokhabov, Dmitry V., Smagina, Inna V., Spirin, Nikolay N., Trushnikova, Tatiana N., Volkova, Larisa I., Zaslavskiy, Leonid G., Zhukova, Natalia G., Ceranic, Mirjana, Cvijanovic, Vera, Drulovic, Jelena, Gavric Kezic, Mira, Jovanovic, Dragoslava, Milicevic, Svetlana K., Raicevic, Ranko, Suknjaja, Vesna, Boskovic Matic, Tatjana, Vojinovic, Slobodan, Ruiz, Luis Brieva, Castillo Trivino, Tamara, Costa-Frossard Franca, Lucienne, Eichau Madueno, Sara, Forero Diaz, Lucia, Martinez, Jose Enrique, Martinez Yelamos, Sergio, Meca Lallana, Virginia, Oreja Guevara, Celia, Ramio i Torrenta, Lluis, Arroyo Gonzalez, Rafael, Guo, Yuh-Cherng, Ro, Long-Sun, Tsai, Nai-Wen, Wang, Kai-Chen, Yang, Fu-Chi, Cherkez, Alla, Deineka, Natalia, Delva, Mykhaylo, Goloborodko, Alla, Hovbakh, Iryna, Khavunka, Marta, Kmyta, Oleksii, Kozyolkin, Olexandr, Lekomtseva, Yevgeniya, Litovchenko, Tetyana, Moskovko, Sergii, Pashkovskyy, Valeriy, Riabichenko, Tetiana, Tovazhnyanska, Olena, Voloshyna, Nataliya, Hrebeniuk, Hanna, Sokolova, Larysa, Arun, Tarunya, Constantinescu, Cris, Harrower, Timothy, Mattoscio, Miriam, Paling, David, Pearson, Owen, Robertson, Neil, Webb, Stewart, Cottrell, David, Nicholas, Richard, Duddy, Martin, Anadani, Nidhiben, Belkin, Martin, Bernitsas, Evanthia, Borazanci, Aimee, Clark, David, Costell, Brian, Delgado, Silvia, Fox, Edward, Gudesblatt, Mark, Gupta, Vipan, Harel, Asaff, Harrison, Daniel, Herrman, Craig, Honeycutt, William David, Hua, Le, Hunter, Samuel, Katsamakis, George, Kilgo, William, Koffman, Boyd, Lindsey, William, Lynch, Sharon G., Mateen, Farrah J., McAllister, Peter, Farahmand, Arya, Morales, Idanis Berrios, Rahmlow, Megan, Naismith, Robert, Napoli, Salvatore, Newman, Stephen, Pardo, Gabriel, Patel, Nirav, Scott, James, Purino, Lorraine, Vasquez, Alberto B., Weisman, David, Wray, Sibyl, Wynn, Daniel, Dihenia, Bhupesh, Obeidat, Ahmed, Ayala, Ricardo, Erwin, April, Betz, Michelle, DeAngelis, Teresa, Osborne Dusan Stefoski, Benjamin, Giang, Daniel, Hendin, Barry, Nagaraj, Arun, Saltis, Lawrence, Singer, Barry, Balabanov, Roumen, Bromley, Steven Michael, Puente, John, Tran, Duc, Kojan, Suleiman, Graves, Jennifer, Fishman, Simon, Maher, Leo, Londono, Diana, Sadiq, Mohamed, Alekseenko, Yuri, Fedulau, Aliaksandr, Kulesh, Sergey, Mikhailova, Elena, Navumava, Halina, Aragon deVecino, Maria Cecilia, Callegaro, Dagoberto, Daccach Marques, Vanessa, Finkelsztejn, Alessandro, Guerreiro, Alexandre, Kleinpaul, Rodrigo, Koiti Sato, Henry, Luiz Longo, Alexandre, Papais Alvarenga, Regina Maria, Pereira Damasceno, Benito, Pereira Gomes Neto, Antonio, Diniz Carneiro, Denise S., Tauil, Carlos Bernardo, Maciel Dias, Ronaldo, Olival, Guilherme, Zago Melo Dias, Paula, de Jesus Carvalho, Margarete, Sato, Douglas Kazutoshi, Forcelini, Cassiano Mateus, Pelov, Plamen, Haralanov, Lyubomir, Ikonomov, Rosen, Ivanov, Ivan, Kastrev, Sasho, Kirilov, Krasimir, Lilovski, Hristo, Maslarov, Dimitar, Staikov, Ivan, Zhelyazkov, Petko, Freedman, Mark, MacLean, Gregg, Marriott, James, McKelvey, John Roger, Girard, Jean-Marc, Vorobeychik, Galina, Morrow, Sarah, Clavelou, Pierre, de Seze, Jerome, Louapre, Celine, Maurousset, Aude, Ruet, Aurelie, Thouvenot, Eric, Morel, Nathalie, Montcuquet, Alexis, Rouhart, Francois, Angstwurm, Klemens, Bayas, Antonios, Bittner, Stefan, Heesen, Christoph, Kowarik, Markus, Marckmann-Boenke, Silke, Muller, Thomas, Zimmermann, Julian, Nelles, Gereon, Paul, Friedemann, Then Bergh, Florian, Wildemann, Brigitte, Zettl, Uwe Klaus, Ziemssen, Tjalf, Doerr, Jan-Marcus, Chroni, Elisabeth, Dardiotis, Efthymios, Doskas, Triantafyllos, Gatzonis, Stylianos, Grigoriadis, Nikolaos, Karageorgiou, Klimentini, Kouremenos, Evangelos, Mitsias, Panayiotis, Spengos, Konstantinos, Kimiskidis, Vasilios, Evangelopoulos, Maria E., Fakas, Nikolaos, Karanasios, Panagiotis, Kyritsis, Athanasios, Maltezou, Maria, Sotirli, Stefania, Tsolaki, Magda, Rohtagi, Anshu, Mukherjee, Joy, Nellikunja, Shankara, Srinivasa, Rangashetty, Sharma, Arvind, Chowdhury, Debashish, Kalita, Jayantee, Brescia Morra, Vincenzo, Centonze, Diego, Gasperini, Claudio, Grimaldi, Luigi, Maniscalco, Giorgia Teresa, Patti, Francesco, Salemi, Giuseppe, Trojano, Maria, Amato, Maria Pia, Malucchi, Simona, Brambilla, Laura, Pozzilli, Carlo, Al Roughani, Raed, Karelis, Guntis, Kalnina, Jolanta, Millers, Andrejs, Mickeviciene, Dalia, Giedraitiene, Natasa, Kazlauskas, Andrius, Malciene, Lina, Joseph, Joyce Pauline, Chung, Law Wan, Looi, Irene, Remli, Rabani, Binti Sapuan, Sapiah, Abdullah, Suhailah, Carbajal Ramirez, Angelica, Espino Ojeda, Alba, Silvestre Bejar Medina, Jesus, Quinones Aguilar, Sandra, Rivas Alonso, Veronica, de la Rosa, Rogelio Francisco, San Juan Orta, Daniel, Misic, Octavian, Odainic, Olesea, Torkildsen, Oivind, Schuler, Stephan, Broch, Line, Canete, Ma. Teresa, Hiyadan, John Harold, Hormillosa, Mary Pauline, Rosales, Raymond L., Adamczyk Sowa, Monika, Bartosik-Psujek, Halina, Berkowicz, Tomasz, Czarnecki, Maciej, Kłodowska, Gabriela, Klosek, Agata, Koscielniak, Jozef, Lisewski, Pawel, Mielcarek, Bartlomiej, Piasecka-Stryczynska, Karolina, Potemkowski, Andrzej, Stasiołek, Mariusz, Krzystanek, Ewa, Lasek-Bal, Anetta, Sikorska, Swietlana, Szczudlik, Andrzej, Gospodarczyk-Szot, Krystyna, Wierzchowska-Cioch, Ewa, K. Jastrzebska, Iwona, Capela, Carlos, Cerqueira, Joao, Correia, Ana Sofia, Correia, Filipe, Ferreira, Joaquim J., Gouveia, Raquel, Mendes, Irene, Nunes, Carla Cecilia, Timoteo, Angela, Veira, Carlos, Martins da Silva, Ana, Domingues, Joana, Chinea, Angel R, Tiu, Cristina, Balasa, Rodica, Chiru, Mirela, Dulamea, Adriana Octaviana, Silviu Manescu, Emilian, Mitrea, Dan, Mitu, Cristina, Nicolae, Silvia Maria, Filip, Carmen Corina Roman, Sabau, Monica, Vanghelie, Doinita, Varga, Ioana, Nunkoo, Vharoon, Agafina, Alina S., Gennadevna, Arefeva Elena, Alexeeva, Tatiana M., Bogdanov, Enver, Dorogov, Nikolay, Doronina, Olga, Goncharova, Zoya, Khasanova, Dina, Korobko, Denis, Pankratov, Evgeny V., Parshina, Elena, Poverennova, Irina, Prokopenko, Semyion V., Sazonov, Denis V., Shkilnyuk, Galina, Sivertseva, Stella, Stolyarov, Igor, Totolyan, Natalia A., Tsukurova, Larisa A., Vorobyeva, Olga V., Voznyuk, Igor A., Zakharova, Maria, Ardashev, Igor V., Boyko, Alexey, Alshehri, Ebtesam, Alkhawajah, Nuha M, Alfugham, Nora, Quek, Amy, Kevin, Tan, Dupejova, Beata, Feketova, Sona, Hancinova, Viera, Jurcaga, Frantisek, Turcani, Peter, Krastev, Georgi, Cimprichova, Andrea, Perichtova, Magdalena, Hojs-Fabjan, Tanja, Horvat Ledinek, Alenka, Savsek, Lina, Bateman, Kathleen, Frost, Andrew Charles, Henning, Franclo, Retief, Chris Francois, Aguado Valcarcel, Marta, Morales, Eduardo Aguera, Alonso Torres, Ana Maria, Borrega Canelo, Laura, Casanova Estruch, Bonaventura, Gascon Gimenez, Francisco, Ayuso, Guillermo I, Martinez Gines, Maria Luisa, Eustasio Meca Lallana, Jose, Rodriguez Antiguedad, Alfredo, Blasco Quilez, Rosario, Brieva Ruiz, Luis, Piehl, Fredrik, Lycke, Jan, Katsarogiannis, Evangelos, Nilsson, Christer, Hoepner, Robert, Zecca, Chiara, Findling, Oliver, Asawavichienjinda, Thanin, Kasemsap, Narongrit, Prayoonwiwat, Naraporn, Mhiri, Chokri, Ağan Yıldırım, Kadriye, Boz, Cavit, Efendi, Husnu, Soysal, Aysun, Terzi, Murat, Uygunoglu, Ugur, Gümüş, Haluk, Mungan, Semra, Ozakbas, Serkan, Serhan Sevim, Mustafa, Tamam, Yusuf, Kale, Nilufer, Karabudak, Rana, Bachinskaya, Natalia, Buchakchyiska, Nataliia, Chmyr, Galyna, Dzyak, Ludmyla, Ivashchenko, Svitlana, Kalbus, Oleksandr, Kareta, Serhiy, Korolova, Oksana, Kostiuchenko, Andrii, Kruchkevych, Zhanna, Larysa, Kadina, Mishchenko, Tamara, Moroz, Olena, Neryanova, Yuliya, Pasiura, Ihor, Pohrebnyak, Oleksandr, Pryshchepa, Volodymyr, Sanotskyy, Yanosh, Shkrobot, Svitlana, Shulga, Olga, Smolanka, Volodymyr, Tomakh, Nataliya, Zhuravlyova, Natalia, Allen, Alison B., Armstrong, Robert, Antezana, Ariel, Baker, Matthew, Bass, Ann, Benenati, Diana, Benson, Dalton, Beretich, Biljana, Burke, Deborah, Calkwood, Jonathan, Carpenter, Adam, Drake, Ryan, Dujmovic Basuroski, Irena, Gupta, Ajay, Hentati, Afif, Kaplan, Jeffrey, Katsafanas, Constance, Keegan, Andrew, Khatri, Bhupendra, Luzzio, Christopher, Malik, Maheen, Bennette, Myers, Miravalle, Augusto, Montoya, Liliana, Nash, Marshall, Poole Pharr, Emily, Sater, Richard A., Scagnelli, John, Schulman, Alan, Shafer, Stuart, Stein, Lee, Vandersluis, Joel, Williams, Armistead, Winkley, James, Berkovich, Regina, Cerghet, Mirela, Horton, Lindsay, Jacobs, Daniel H., Laurin, Nida, Liow, Kore, Robertson, Derrick, Mattson, David, Cabrera, Alicia V., Leist, Thomas, Negroski, Donald, Royter, Vladimir, LaGanke, Christopher, Winner, Paul, Sweeney, Michael, Weinberg, Lawrence A., Smith, Andrew, Rivas-Rodriguez, Erica, Wagner, Kimberly, Montalban, Xavier, Vermersch, Patrick, Arnold, Douglas L, Bar-Or, Amit, Cree, Bruce A C, Cross, Anne H, Kubala Havrdova, Eva, Kappos, Ludwig, Stuve, Olaf, Wiendl, Heinz, Wolinsky, Jerry S, Dahlke, Frank, Le Bolay, Claire, Shen Loo, Li, Gopalakrishnan, Sathej, Hyvert, Yann, Javor, Andrija, Guehring, Hans, Tenenbaum, Nadia, and Tomic, Davorka

Published
2024
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5. Treating to target in multiple sclerosis: Do we know how to measure whether we hit it?

Author

Bsteh, Gabriel, Krajnc, Nik, Altmann, Patrick, Hendin, Barry, Bharadia, Trishna, Jaruszowic, Sonja, Lublin, Fred, Oh, Jiwon, Parow, Detlev, Ribbens, Annemie, Shields, Aoife, Smeets, Dirk, Thouvenot, Eric, Chan, Andrew, and Berger, Thomas

Subjects
MULTIPLE sclerosis, DIGITAL divide, DEFINITIONS
Abstract

Background and purpose: The rapidly evolving landscape of effective treatment options in multiple sclerosis has led to a shift of treatment objectives towards a treat‐to‐target approach aiming to suppress disease activity below the level of detectability early during the disease. To enable treat‐to‐target, a thorough reappraisal of available outcome measures with respect to their ability in this regard is required. Methods: To that end, we conducted a comprehensive systematic literature review of more than 1000 studies using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) 2020 methodology focusing on underlying evidence as well as utility and implementability in clinical practice. Results: From there, we propose a set of measurable outcomes for everyday routine clinical practice as well as advanced/aspirational measurables requiring additional resources. We also outline remaining knowledge/technology gaps that need to be overcome to enable a treat‐to‐target approach. Conclusions: This work provides the basis for an evidence‐based definition of outcome targets for relevant stakeholders and regulatory authorities. [ABSTRACT FROM AUTHOR]

Published
2024
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7. One-year Analysis of Efficacy and Safety Data from Black/African American and Hispanic/Latino People with Relapsing Multiple Sclerosis Receiving Ocrelizumab Treatment in the CHIMES Trial (PL5.005)

Author

Amezcua, Lilyana, primary, Monson, Nancy, additional, Williams, Mitzi, additional, Vartanian, Timothy, additional, Reder, Anthony, additional, Pandey, Krupa, additional, Rammohan, Kottil, additional, Hendin, Barry, additional, Wu, Gregory, additional, Parekh, Rikisha, additional, Pei, Jinglan, additional, Abioye, Ibraheem, additional, Acosta, Juan, additional, and Bernitsas, Evanthia, additional

Published
2024
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9. Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY): a randomised, placebo-controlled, phase 2 trial

Author

Agüera Morales, Eduardo, Al Khedr, Abdullatif, Ampapa, Radek, Arroyo, Rafael, Belkin, Martin, Bonek, Robert, Boyko, Alexey, Capra, Ruggero, Centonze, Diego, Clavelou, Pierre, Debouverie, Marc, Drulovic, Jelena, Edwards, Keith, Evangelou, Nikos, Evdoshenko, Evgeniy, Fernández, Oscar, Fernández Sánchez, Victoria, Freedman, Mark, Freedman, Steven, Fryze, Waldemar, Garcia-Merino, Antonio, Gavric-Kezic, Mira, Ghezzi, Angel, Gout, Olivier, Grimaldi, Luigi, Hendin, Barry, Hertmanowska, Hanka, Hintzen, Rogier, Hradilek, Pavel, Hupperts, Raymond, Ilkowski, Jan, Ivashinenkova, Evelina, Izquierdo, Guillermo, Jacques, Francois, Jakab, Gabor, Khabirov, Farit, Klodowska-Duda, Gabriela, Komoly, Samuel, Kostic, Smiljana, Kovarova, Ivana, Kremenchuzky, Marcelo, Laganke, Christopher, LaPierre, Yves, Maciejowski, Maciej, Maison, Francois Grand, Marfia, Girolama Alessandra, Martínez Yélamos, Sergio, Meluzinova, Eva, Montalban, Xavier, Murray, Ronald, Naismith, Robert, Newsome, Scott, Nguyen, Viet, Oreja, Delia, Pardo, Gabriel, Pasechnik, Elena, Patti, Francesco, Potemkowski, Andrzej, Prokopenko, Semen, Qian, Peiqing, Rodríguez-Antigüedad, Alfredo, Rossman, Howard, Rozsa, Csilla, Sánchez López, Fernando, Selmaj, Krzysztof, Silber, Eli, Stepien, Adam, Stepniewska, Anna, Swiat, Maciej, Toncev, Gordana, Tourbah, Ayman, Trushnikova, Tatyana, Uccelli, Antonio, Vachova, Marta, Valis, Martin, Vecsei, Laszlo, Wiertlewski, Sandrine, Zaffaroni, Mauro, Zielinski, Tomasz, Cadavid, Diego, Mellion, Michelle, Edwards, Keith R, Calabresi, Peter A, Drulović, Jelena, Giovannoni, Gavin, Hartung, Hans-Peter, Arnold, Douglas L, Fisher, Elizabeth, Rudick, Richard, Mi, Sha, Chai, Yi, Li, Jie, Zhang, Yiwei, Cheng, Wenting, Xu, Lei, Zhu, Bing, Green, Susan M, Chang, Ih, Deykin, Aaron, and Sheikh, Sarah I

Published
2019
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13. Interferons and Multiple Sclerosis: Lessons from 25 Years of Clinical and Real-World Experience with Intramuscular Interferon-Beta-1a (Avonex)

Author

Cohan, Stanley, Hendin, Barry, Reder, Anthony, Smoot, Kyle, Avila, Robin, Mendoza, Jason, and Weinstock-Guttman, Bianca

Subjects
allergology
Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The interferons (IFNs) were discovered in 1957, and recombinant IFN-β-1b was approved by the US Food and Drug Administration as the first disease-modifying therapy (DMT) for MS in 1993. Since that time, clinical trials and real-world observational studies have demonstrated the effectiveness of IFN therapies. The pivotal intramuscular IFN-β-1a phase 3 trial was the first to demonstrate that a DMT could reduce accumulation of sustained disability in MS. Patient adherence to treatment is higher with intramuscular IFN-β-1a, given once weekly, than with subcutaneous formulations requiring multiple injections per week. Moreover, subcutaneous IFN-β-1a is associated with an increased incidence of injection site reactions and neutralizing antibodies compared with intramuscular administration. In recent years, revisions to MS diagnostic criteria have improved clinicians’ ability to identify patients with MS and have promoted the use of magnetic resonance imaging (MRI) for diagnosis and monitoring. MRI studies show that treatment with IFN-β-1a, relative to placebo, reduces T2 and gadolinium-enhancing lesions and gray matter atrophy. Since the approval of intramuscular IFN-β-1a, several high-efficacy therapies have been approved for MS, though the benefit of these high-efficacy therapies should be balanced against the increased risk of serious adverse events. For some subpopulations of patients, including pregnant women, the safety profile of IFN-β formulations may provide a particular benefit. In addition, the antiviral properties of IFNs may indicate therapeutic opportunities for IFN-β in the treatment of viral infections such as COVID-19.

Published
2021

16. Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration

Author

Franzmeier, Nicolai, Suárez-Calvet, M., Kleinberger, Gernot, Doraiswamy, P Murali, Petrella, Jeffrey R, Arnold, Steven E, Karlawish, Jason H, Wolk, David, Smith, Charles D, Jicha, Greg, Hardy, Peter, Lopez, Oscar L, Oakley, Mary Ann, Haass, Christian, Simpson, Donna M, Ismail, M Saleem, Brand, Connie, Mulnard, Ruth A, Thai, Gaby, Mc-Adams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I, Ewers, Michael, Lah, James J, Cellar, Janet S, Burns, Jeffrey M, Anderson, Heather S, Swerdlow, Russell H, Bartzokis, George, Silverman, Daniel H S, Lu, Po H, Apostolova, Liana, Graff-Radford, Neill R, Initiative, Alzheimer’s Disease Neuroimaging, Parfitt, Francine, Johnson, Heather, Farlow, Martin, Herring, Scott, Hake, Ann M, van Dyck, Christopher H, Carson, Richard E, MacAvoy, Martha G, Chertkow, Howard, Bergman, Howard, Weiner, Michael, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Hsiung, Ging-Yuek Robin, Feldman, Howard, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Aisen, Paul, Bernick, Charles, Munic, Donna, Wu, Chuang-Kuo, Johnson, Nancy, Mesulam, Marsel, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Novak, Gerald, Reynolds, Brigid, Sperling, Reisa A, Frey, Meghan, Johnson, Keith A, Rosen, Allyson, Tinklenberg, Jared, Ashford, Wes, Sabbagh, Marwan, Belden, Christine, Jacobson, Sandra, Green, Robert C, Killiany, Ronald, Norbash, Alexander, Nair, Anil, Obisesan, Thomas O, Wolday, Saba, Bwayo, Salome K, Lerner, Alan, Hudson, Leon, Ogrocki, Paula, Fletcher, Evan, Montine, Tom, Carmichael, Owen, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Potkin, Steven G, Preda, Adrian, Petersen, Ronald, Nguyen, Dana, Tariot, Pierre, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Hendin, Barry A, Scharre, Douglas W, Kataki, Maria, Frontzkowski, Lukas, Gamst, Anthony, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Hosp, Hartford, Pearlson, Godfrey D, Blank, Karen, Anderson, Karen, Santulli, Robert B, Schwartz, Eben S, Williamson, Jeff D, Thomas, Ronald G, Sink, Kaycee M, Watkins, Franklin, Ott, Brian R, Querfurth, Henry, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Donohue, Michael, Mintzer, Jacobo, Longmire, Crystal Flynn, Spicer, Kenneth, Walter, Sarah, Gessert, Devon, Sather, Tamie, Beckett, Laurel, Harvey, Danielle, Kornak, John, Jack, Clifford R, Moore, Annah, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Jagust, William, Bandy, Dan, Hohman, Timothy J, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Morris, John, Cairns, Nigel J, Taylor-Reinwald, Lisa, Trojanowki, J. Q., Shaw, Les, Morenas-Rodriguez, Estrella, Lee, Virginia M Y, Korecka, Magdalena, Toga, Arthur W, Crawford, Karen, Neu, Scott, Saykin, Andrew J, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Nuscher, Brigitte, Frank, Richard, Snyder, Peter J, Molchan, Susan, Kaye, Jeffrey, Dolen, Sara, Quinn, Joseph, Schneider, Lon S, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Shaw, Leslie, Vanderswag, Helen, Heidebrink, Judith L, Lord, Joanne L, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Trojanowski, John Q, Morris, John C, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Mitsis, Effie, Romirowsky, Aliza, deToledo-Morrell, Leyla, Dichgans, Martin, Shah, Raj C, Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn, Onyike, Chiadi, Kielb, Stephanie, Rusinek, Henry, de Leon, Mony J, and Glodzik, Lidia

Subjects
Male, Aging, pathology [Cognitive Dysfunction], Apolipoprotein E4, Cognitive decline, genetics [Alzheimer Disease], Neurodegenerative, lcsh:Geriatrics, Alzheimer's Disease, lcsh:RC346-429, pathology [Alzheimer Disease], Immunologic, Receptors, 80 and over, 2.1 Biological and endogenous factors, sTREM2, Microglial activation, Aetiology, Receptors, Immunologic, genetics [Apolipoprotein E4], Aged, 80 and over, Membrane Glycoproteins, pathology [Nerve Degeneration], cerebrospinal fluid [Alzheimer Disease], cerebrospinal fluid [Cognitive Dysfunction], Neurological, Female, cerebrospinal fluid [Membrane Glycoproteins], Alzheimer’s disease, Research Article, Clinical Sciences, ApoE4, Clinical Research, Alzheimer Disease, ddc:570, Acquired Cognitive Impairment, Genetics, Humans, Cognitive Dysfunction, Genetic Predisposition to Disease, Neurodegeneration, lcsh:Neurology. Diseases of the nervous system, Aged, Neurology & Neurosurgery, Neurosciences, genetics [Cognitive Dysfunction], Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer’s Disease Neuroimaging Initiative, Brain Disorders, lcsh:RC952-954.6, Nerve Degeneration, Dementia
Abstract

Background The Apolipoprotein E ε4 allele (i.e. ApoE4) is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). TREM2 (i.e. Triggering receptor expressed on myeloid cells 2) is a microglial transmembrane protein brain that plays a central role in microglia activation in response to AD brain pathologies. Whether higher TREM2-related microglia activity modulates the risk to develop clinical AD is an open question. Thus, the aim of the current study was to assess whether higher sTREM2 attenuates the effects of ApoE4-effects on future cognitive decline and neurodegeneration. Methods We included 708 subjects ranging from cognitively normal (CN, n = 221) to mild cognitive impairment (MCI, n = 414) and AD dementia (n = 73) from the Alzheimer’s disease Neuroimaging Initiative. We used linear regression to test the interaction between ApoE4-carriage by CSF-assessed sTREM2 levels as a predictor of longitudinally assessed cognitive decline and MRI-assessed changes in hippocampal volume changes (mean follow-up of 4 years, range of 1.7-7 years). Results Across the entire sample, we found that higher CSF sTREM2 at baseline was associated with attenuated effects of ApoE4-carriage (i.e. sTREM2 x ApoE4 interaction) on longitudinal global cognitive (p = 0.001, Cohen’s f 2 = 0.137) and memory decline (p = 0.006, Cohen’s f 2 = 0.104) as well as longitudinally assessed hippocampal atrophy (p = 0.046, Cohen’s f 2 = 0.089), independent of CSF markers of primary AD pathology (i.e. Aβ1–42, p-tau181). While overall effects of sTREM2 were small, exploratory subanalyses stratified by diagnostic groups showed that beneficial effects of sTREM2 were pronounced in the MCI group. Conclusion Our results suggest that a higher CSF sTREM2 levels are associated with attenuated ApoE4-related risk for future cognitive decline and AD-typical neurodegeneration. These findings provide further evidence that TREM2 may be protective against the development of AD.

Published
2020
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17. Supplemental material for Patients transitioning from non-pegylated to pegylated interferon beta-1a have a low risk of new flu-like symptoms: ALLOW phase 3b trial results

Author

Naismith, Robert T, Hendin, Barry, Wray, Sibyl, Huang, DeRen, Gaudenzi, Fiorenza, Qunming Dong, Sperling, Bjørn, Mann, Monica, and Werneburg, Brian

Subjects
FOS: Clinical medicine, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental Material for Patients transitioning from non-pegylated to pegylated interferon beta-1a have a low risk of new flu-like symptoms: ALLOW phase 3b trial results by Robert T Naismith, Barry Hendin, Sibyl Wray, DeRen Huang, Fiorenza Gaudenzi, Qunming Dong, Bjørn Sperling, Monica Mann and Brian Werneburg in Multiple Sclerosis Journal—Experimental, Translational and Clinical

Published
2019
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21. (DMT33) One-Year Analysis of Ocrelizumab Treatment in Black/African American and Hispanic/Latino Patients With Relapsing Multiple Sclerosis From the CHIMES Trial.

Author

Amezcua, Lilyana, Monson, Nancy L., Williams, Mitzi J., Vartanian, Timothy, Reder, Anthony T., Pandey, Krupa, Rammohan, Kottil, Hendin, Barry, Wu, Gregory F., Parekh, Rikisha, Jinglan Pei, Abioye, Ibraheem, Acosta, Juan, and Bernitsas, Evanthia

Subjects
THERAPEUTIC use of monoclonal antibodies, MULTIPLE sclerosis, AFRICAN Americans, HISPANIC Americans, CLINICAL trials, TREATMENT effectiveness, CONFERENCES & conventions, DISEASE relapse, TIME
Abstract

BACKGROUND: Black/African American and Hispanic/Latino individuals are understudied in clinical trials but may have higher multiple sclerosis (MS) incidence, faster disease progression, and/or increased risk of disability progression vs White individuals. OBJECTIVES: CHIMES (NCT04377555), the first trial of its kind, was designed to evaluate outcomes with ocrelizumab in Black/African American and Hispanic/Latino patients with relapsing MS (BpwRMS; HpwRMS). METHODS: This prospective, open-label, single-arm, phase 4 study included BpwRMS and HpwRMS aged 18 to 65 years with baseline Expanded Disability Status Scale (EDSS) scores of 0 to 5.5. Participants received two 300-mg ocrelizumab infusions 14 days apart and 600 mg every 24 weeks for 1 year, with an optional 3-year extension. The primary end point was 48-week no evidence of disease activity (NEDA), defined as proportion of patients free from protocol-defined events (relapse, 24-week confirmed disability progression [24W-CDP], and T1 gadolinium-enhancing lesions [GdELs] or new/enlarging T2 lesions [NET2Ls]). Safety (eg, adverse events [AEs]) was also assessed. Participants were periodically surveyed with the Work Productivity and Activity Impairment Questionnaire (WPAI) during the study. RESULTS: Of 182 participants, 113 (62%) were Black/ African American and 69 (38%) were Hispanic/Latino. Mean age was 35.5 years (SD, 10.5), body mass index was 31 kg/m2 (SD, 7.4), and 72.5% were women. Mean times since first MS symptoms and RMS diagnosis were 4.9 (SD, 5.7) and 2.9 (SD, 4.5) years, respectively. Baseline mean EDSS score was 2.4 (SD, 1.4). Approximately half of BpwRMS (46.0%) and HpwRMS (58.0%) achieved 48-week NEDA. Most BpwRMS and HpwRMS had no relapses (94.7% and 95.7%, respectively), 24W-CDP (94.7% and 94.2%), or GdELs (94.7% and 97.1%). No NET2Ls were observed in 46% of BpwRMS and 63.8% of HpwRMS. No deaths occurred; 80.2% had ≥ 1 AE, 5.5% had ≥ 1 serious AE, and 29.1% had infusion-related reactions. Among the total CHIMES population, WPAI scores decreased (less impairment) for each domain, including mean changes from baseline of -5.5 (SD, 27.2) for absenteeism, -1.6 (SD, 27.4) for presenteeism, -5.5 (SD, 30.5) for work productivity, and -6.1 (SD, 28.5) for activity impairment. CONCLUSIONS: These results are consistent with those of prior studies and suggest that ocrelizumab is a suitable treatment in this understudied population, as shown by control of MS disease activity, consistent safety signals, and trend toward improved work productivity after 1 year of treatment. [ABSTRACT FROM AUTHOR]

Published
2024

22. Treatment satisfaction significantly improves in patients with multiple sclerosis switching from interferon beta therapy to peginterferon beta-1a every 2 weeks

Author

Hendin,Barry, Naismith,Robert, Wray,Sibyl E, Huang,Deren, Dong,Qunming, Livingston,Terrie, Jones,Daniel, Watson,Crystal, Jhaveri,Mehul, Hendin,Barry, Naismith,Robert, Wray,Sibyl E, Huang,Deren, Dong,Qunming, Livingston,Terrie, Jones,Daniel, Watson,Crystal, and Jhaveri,Mehul

Abstract

Barry Hendin,1 Robert T Naismith,2 Sibyl E Wray,3 Deren Huang,4 Qunming Dong,5 Terrie Livingston,6 Daniel L Jones,6 Crystal Watson,7 Mehul Jhaveri6 1Phoenix Neurological Associates, Phoenix, AZ, USA; 2Department of Neurology, Washington University School of Medicine, St Louis, MO, USA; 3Hope Neurology MS Center, Knoxville, TN, USA; 4Mount Carmel Neuroscience and MDH Research, Westerville, OH, USA; 5Biostatistics, Biogen, Cambridge, MA, USA; 6US Medical, Biogen, Cambridge, MA, USA; 7Global Value and Access, Biogen, Cambridge, MA, USA Objectives: Posthoc analysis of treatment satisfaction in patients switching to subcutaneous (SC) peginterferon beta-1a in the ALLOW study.Patients and methods: Patients with relapsing multiple sclerosis treated with intramuscular interferon (IFN) beta-1a or SC IFN beta-1a or beta-1b remained on their current therapy for a 4-week run-in period, followed by a switch to SC peginterferon beta-1a 125 mcg every 2 weeks for 48 weeks. Treatment satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM), which covers effectiveness, side effects, convenience, and global satisfaction. Patients completed the TSQM at baseline (prior to starting the 4-week run-in period) and 4, 12, 24, 36, and 48 weeks after switching, and scores were analyzed for the overall population and compared to baseline. Patients reported the severity of flu-like symptoms (FLS) at baseline and with each peginterferon beta-1a injection; clinicians evaluated the occurrence of injection-site reactions (ISRs) after the first dose of peginterferon beta-1a and every 12 weeks thereafter. TSQM scores were stratified by the presence of FLS or ISRs during the study period and by prior IFN therapy use.Results: For the overall population (n=194), convenience and global satisfaction scores significantly improved from baseline at all time points, and side effect satisfaction scores significantly improved up to week 36. Convenience scores significantly im

Published
2018

23. 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

24. Body mass index is associated with biological CSF markers of core brain pathology of Alzheimer's disease

Author

Ewers, Michael, Schmitz, Susanne, Vellas, Bruno, Morris, John C, Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Dubois, Bruno, Mitsis, Effie, Romirowsky, Aliza, deToledo-Morrell, Leyla, Shah, Raj C, Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn, Onyike, Chiadi, Kielb, Stephanie, Blennow, Kaj, Rusinek, Henry, de Leon, Mony J, Glodzik, Lidia, Doraiswamy, P Murali, Petrella, Jeffrey R, Coleman, R Edward, Arnold, Steven E, Karlawish, Jason H, Wolk, David, Smith, Charles D, Buerger, Katharina, Jicha, Greg, Hardy, Peter, Lopez, Oscar L, Oakley, MaryAnn, Simpson, Donna M, Porsteinsson, Anton P, Goldstein, Bonnie S, Martin, Kim, Makino, Kelly M, Ismail, M Saleem, Teipel, Stefan J, Brand, Connie, Mulnard, Ruth A, Thai, Gaby, Mc-Adams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I, Lah, James J, Cellar, Janet S, Weiner, Michael, Burns, Jeffrey M, Anderson, Heather S, Swerdlow, Russell H, Apostolova, Liana, Lu, Po H, Bartzokis, George, Silverman, Daniel H S, Graff-Radford, Neill R, Parfitt, Francine, Johnson, Heather, Hampel, Harald, Farlow, Martin, Herring, Scott, Hake, Ann M, van Dyck, Christopher H, Carson, Richard E, MacAvoy, Martha G, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Initiative, Alzheimer's Disease Neuroimaging, Stefanovic, Bojana, Caldwell, Curtis, Hsiung, Ging-Yuek Robin, Feldman, Howard, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Kerwin, Diana, Mesulam, Marek-Marsel, Lipowski, Kristina, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Aisen, Paul, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Marshall, Gad, Frey, Meghan, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan, Belden, Christine, Jacobson, Sandra, Hansson, Oskar, Kowall, Neil, Killiany, Ronald, Budson, Andrew E, Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O, Wolday, Saba, Bwayo, Salome K, Lerner, Alan, Hudson, Leon, Ogrocki, Paula, Fletcher, Evan, Carmichael, Owen, Olichney, John, DeCarli, Charles, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, Johnson, Sterling, Petersen, Ronald, Asthana, Sanjay, Carlsson, Cynthia M, Potkin, Steven G, Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Jack, Clifford R, Rainka, Michelle, Hendin, Barry A, Scharre, Douglas W, Kataki, Maria, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Pearlson, Godfrey D, Blank, Karen, Anderson, Karen, Jagust, William, Saykin, Andrew J, Santulli, Robert B, Schwartz, Eben S, Sink, Kaycee M, Williamson, Jeff D, Garg, Pradeep, Watkins, Franklin, Ott, Brian R, Querfurth, Henry, Tremont, Geoffrey, Trojanowki, John Q, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Mintzer, Jacobo, Longmire, Crystal Flynn, Spicer, Kenneth, Toga, Arthur W, Beckett, Laurel, Green, Robert C, Walsh, Cathal, Morris, John, Liu, Enchi, Montine, Tom, Gamst, Anthony, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Fitzpatrick, Annette, Gessert, Devon, Sather, Tamie, Harvey, Danielle, Kornak, John, Dale, Anders, Bernstein, Matthew, Bennett, David, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Minthon, Lennart, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Cairns, Nigel J, Taylor-Reinwald, Lisa, Trojanowki, J. Q., Shaw, Les, Lee, Virginia M Y, Korecka, Magdalena, Trojanowski, John Q, Crawford, Karen, Neu, Scott, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J, Shaw, Leslie M, Molchan, Susan, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Faluyi, Yetunde O, Heidebrink, Judith L, Lord, Joanne L, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, and Bell, Karen L

Subjects
Male, Apolipoprotein E, Aging, Pathology, Neurology, epidemiology [Alzheimer Disease], Statistics as Topic, cerebrospinal fluid [Amyloid beta-Peptides], Comorbidity, Body Mass Index, Cerebrospinal fluid, pathology [Brain], Prevalence, Aged, 80 and over, biology, General Neuroscience, Brain, Middle Aged, Prognosis, amyloid beta-protein (1-42), cerebrospinal fluid [Cognition Disorders], cerebrospinal fluid [Alzheimer Disease], cerebrospinal fluid [Biomarkers], Biomarker (medicine), Female, epidemiology [United States], Alzheimer's disease, Psychology, Alzheimer's Disease Neuroimaging Initiative, epidemiology [Cognition Disorders], medicine.medical_specialty, Tau protein, tau Proteins, Alzheimer Disease, medicine, Humans, ddc:610, cerebrospinal fluid [Peptide Fragments], Aged, Amyloid beta-Peptides, medicine.disease, United States, Peptide Fragments, cerebrospinal fluid [tau Proteins], metabolism [Brain], biology.protein, pathology [Cognition Disorders], Neurology (clinical), Geriatrics and Gerontology, Cognition Disorders, Body mass index, Biomarkers, Developmental Biology
Abstract

Weight changes are common in aging and Alzheimer's disease (AD) and postmortem findings suggest a relation between lower body mass index (BMI) and increased AD brain pathology. In the current multicenter study, we tested whether lower BMI is associated with higher core AD brain pathology as assessed by cerebrospinal fluid (CSF)-based biological markers of AD in 751 living subjects: 308 patients with AD, 296 subjects with amnestic mild cognitive impairment (MCI), and 147 elderly healthy controls (HC). Based upon a priori cutoff values on CSF concentration of total tau and beta-amyloid (Aβ(1-42)), subjects were binarized into a group with abnormal CSF biomarker signature (CSF+) and those without (CSF-). Results showed that BMI was significantly lower in the CSF+ when compared with the CSF- group (F = 27.7, df = 746, p0.001). There was no interaction between CSF signature and diagnosis or apolipoprotein E (ApoE) genotype. In conclusion, lower BMI is indicative of AD pathology as assessed with CSF-based biomarkers in demented and nondemented elderly subjects.

Published
2012
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26. Comparison of Visual and Quantitative Florbetapir F 18 Positron Emission Tomography Analysis in Predicting Mild Cognitive Impairment Outcomes

Author

Schreiber, Stefanie, Landau, Susan M, Gamst, Anthony, Cellar, Janet S, Burns, Jeffrey M, Anderson, Heather S, Laubinger, Mary M, Bartzokis, George, Silverman, Daniel H S, Lu, Po H, Graff-Radford, Neill R, Parfitt, Francine, Johnson, Heather, Soares, Holly, Farlow, Martin, Herring, Scott, Hake, Ann M, van Dyck, Christopher H, MacAvoy, Martha G, Benincasa, Amanda L, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Green, Robert C, Graham, Simon, Caldwell, Curtis, Hsiung, Ging-Yuek Robin, Feldman, Howard, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Montine, Tom, Wu, Chuang-Kuo, Johnson, Nancy, Mesulam, Marsel, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Scott, Johnson, Kathleen B, Behan, Kelly E, Sperling, Reisa A, Thomas, Ronald G, Rentz, Dorene M, Johnson, Keith A, Rosen, Allyson, Tinklenberg, Jared, Ashford, Wes, Sabbagh, Marwan, Connor, Donald, Jacobson, Sandra, Killiany, Ronald, Norbash, Alexander, Donohue, Michael, Nair, Anil, Obisesan, Thomas O, Jayam-Trouth, Annapurni, Wang, Paul, Lerner, Alan, Hudson, Leon, Ogrocki, Paula, DeCarli, Charles, Fletcher, Evan, Carmichael, Owen, Walter, Sarah, Kittur, Smita, Mirje, Seema, Borrie, Michael, Lee, T-Y, Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Potkin, Steven G, Preda, Adrian, Dale, Anders, Nguyen, Dana, Tariot, Pierre, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Hendin, Barry A, Scharre, Douglas W, Kataki, Maria, Bernstein, Matthew, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Gandy, Sam, Marenberg, Marjorie E, Rovner, Barry W, Pearlson, Godfrey, Blank, Karen, Anderson, Karen, Saykin, Andrew J, Felmlee, Joel, Santulli, Robert B, Englert, Jessica, Williamson, Jeff D, Sink, Kaycee M, Watkins, Franklin, Ott, Brian R, Cohen, Ronald, Salloway, Stephen, Malloy, Paul, Fero, Allison, Fox, Nick, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Mintzer, Jacobo, Thompson, Paul, Schuff, Norbert, Alexander, Gene, Bandy, Dan, Chen, Kewei, Morris, John, Lee, Virginia M-Y, Korecka, Magdalena, Schreiber, Frank, Crawford, Karen, Neu, Scott, Harvey, Danielle, Kornak, John, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Buckholtz, Neil, Kaye, Jeffrey, Jagust, William J, Dolen, Sara, Quinn, Joseph, Schneider, Lon, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Heidebrink, Judith L, Lord, Joanne L, Petersen, Ronald, Initiative, Alzheimer's Disease Neuroimaging, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Morris, John C, Mintun, Mark A, Schneider, Stacy, Aisen, Paul, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Tang, Cheuk, Marzloff, George, deToledo-Morrell, Leyla, Shah, Raj C, Duara, Ranjan, Varon, Daniel, Jack, Clifford R, Roberts, Peggy, Albert, Marilyn S, Pedroso, Julia, Toroney, Jaimie, Rusinek, Henry, de Leon, Mony J, De Santi, Susan M, Doraiswamy, P Murali, Petrella, Jeffrey R, Aiello, Marilyn, Toga, Arthur W, Clark, Christopher M, Pham, Cassie, Nunez, Jessica, Smith, Charles D, Given, Curtis A, Hardy, Peter, Lopez, Oscar L, Oakley, MaryAnn, Simpson, Donna M, Ismail, M Saleem, Beckett, Laurel, Brand, Connie, BA, Jennifer Richard, Mulnard, Ruth A, Thai, Gaby, Mc-Adams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I, and Lah, James J

Subjects
Male, medicine.medical_specialty, diagnostic imaging [Cognitive Dysfunction], metabolism [Amyloid beta-Peptides], Context (language use), Standardized uptake value, Neuroimaging, Alzheimer Disease, Fluorodeoxyglucose F18, Predictive Value of Tests, medicine, Humans, Cognitive Dysfunction, therapy [Cognitive Dysfunction], ddc:610, Longitudinal Studies, Psychiatry, Aged, Aged, 80 and over, Amyloid beta-Peptides, medicine.diagnostic_test, therapy [Alzheimer Disease], business.industry, methods [Positron-Emission Tomography], diagnosis [Alzheimer Disease], complications [Alzheimer Disease], Middle Aged, medicine.disease, Inter-rater reliability, Treatment Outcome, Positron emission tomography, Positron-Emission Tomography, Predictive value of tests, Biomarker (medicine), Female, Neurology (clinical), Alzheimer's disease, Psychology, Nuclear medicine, business, analysis [Biomarkers], complications [Cognitive Dysfunction], Biomarkers
Abstract

Importance The applicability of β-amyloid peptide (Aβ) positron emission tomography (PET) as a biomarker in clinical settings to aid in selection of individuals at preclinical and prodromal Alzheimer disease (AD) will depend on the practicality of PET image analysis. In this context, visual-based Aβ PET assessment seems to be the most feasible approach. Objectives To determine the agreement between visual and quantitative Aβ PET analysis and to assess the ability of both techniques to predict conversion from mild cognitive impairment (MCI) to AD. Design, Setting, and Participants A longitudinal study was conducted among the Alzheimer’s Disease Neuroimaging Initiative (ADNI) sites in the United States and Canada during a 1.6-year mean follow-up period. The study was performed from September 21, 2010, to August 11, 2014; data analysis was conducted from September 21, 2014, to May 26, 2015. Participants included 401 individuals with MCI receiving care at a specialty clinic (219 [54.6%] men; mean [SD] age, 71.6 [7.5] years; 16.2 [2.7] years of education). All participants were studied with florbetapir F 18 [ 18 F] PET. The standardized uptake value ratio (SUVR) positivity threshold was 1.11, and one reader rated all images, with a subset of 125 scans rated by a second reader. Main Outcomes and Measures Sensitivity and specificity of positive and negative [ 18 F] florbetapir PET categorization, which was estimated with cerebrospinal fluid Aβ1-42 as the reference standard. Risk for conversion to AD was assessed using Cox proportional hazards regression models. Results The frequency of Aβ positivity was 48.9% (196 patients; visual analysis), 55.1% (221 patients; SUVR), and 64.8% (166 patients; cerebrospinal fluid), yielding substantial agreement between visual and SUVR data (κ = 0.74) and between all methods (Fleiss κ = 0.71). For approximately 10% of the 401 participants in whom visual and SUVR data disagreed, interrater reliability was moderate (κ = 0.44), but it was very high if visual and quantitative results agreed (κ = 0.92). Visual analysis had a lower sensitivity (79% vs 85%) but higher specificity (96% vs 90%), respectively, compared with SUVR. The conversion rate was 15.2% within a mean of 1.6 years, and a positive [ 18 F] florbetapir baseline scan was associated with a 6.91-fold (SUVR) or 11.38-fold (visual) greater hazard for AD conversion, which changed only modestly after covariate adjustment for apolipoprotein e4, concurrent fludeoxyglucose F 18 PET scan, and baseline cognitive status. Conclusions and Relevance Visual and SUVR Aβ PET analysis may be equivalently used to determine Aβ status for individuals with MCI participating in clinical trials, and both approaches add significant value for clinical course prognostication.

Published
2015
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28. Predicting missing biomarker data in a longitudinal study of Alzheimer disease

Author

Lo, Raymond Y., Jagust, William J., Aisen, Paul, Jack, Clifford R., Toga, Arthur W., Beckett, Laurel, Gamst, Anthony, Soares, Holly, C. Green, Robert, Montine, Tom, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Chen, Kewei, Morris, John, Lee, Virginia M.-Y., Korecka, Magdalena, Crawford, Karen, Neu, Scott, Harvey, Danielle, Kornak, John, Saykin, Andrew J., Foroud, Tatiana M., Potkin, Steven, Shen, Li, Buckholtz, Neil, Kaye, Jeffrey, Dolen, Sara, Quinn, Joseph, Schneider, Lon, Pawluczyk, Sonia, Spann, Bryan M., Brewer, James, Vanderswag, Helen, Heidebrink, Judith L., Lord, Joanne L., Petersen, Ronald, Johnson, Kris, Doody, Rachelle S., Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Morris, John C., Mintun, Mark A., Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Tang, Cheuk, Marzloff, George, Toledo-Morrell, Leylade, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn S., Pedroso, Julia, Toroney, Jaimie, Rusinek, Henry, de Leon, Mony J, De Santi, Susan M, Doraiswamy, P. Murali, Petrella, Jeffrey R., Aiello, Marilyn, Clark, Christopher M., Pham, Cassie, Nunez, Jessica, Smith, Charles D., Given, Curtis A., Hardy, Peter, Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Ismail, M. Saleem, Brand, Connie, Richard, Jennifer, Mulnard, Ruth A., Thai, Gaby, Mc-Adams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Laubinger, Mary M., Bartzokis, George, Silverman, Daniel H.S., Lu, Po H., Graff-Radford MBBCH, Neill R, Parfitt, Francine, Johnson, Heather, Farlow, Martin, Herring, Scott, Hake, Ann M., van Dyck, Christopher H., MacAvoy, Martha G., Benincasa, Amanda L., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Graham, Simon, Caldwell, Curtis, Hsiung, Ging-Yuek Robin, Feldman, Howard, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Wu, Chuang-Kuo, Johnson, Nancy, Mesulam, Marsel, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Scott, Johnson, Kathleen B., Behan, Kelly E., Sperling, Reisa A., Rentz, Dorene M., Johnson, Keith A., Rosen, Allyson, Tinklenberg, Jared, Ashford, Wes, Sabbagh, Marwan, Connor, Donald, Jacobson, Sandra, Killiany, Ronald, Norbash, Alexander, Nair, Anil, Obisesan, Thomas O., Jayam-Trouth, Annapurni, Wang, Paul, Lerner, Alan, Hudson, Leon, Ogrocki, Paula, Fletcher, Evan, Carmichael, Owen, Kittur, Smita, Mirje, Seema, Borrie, Michael, Lee, T-Y, Bartha, Dr Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Hendin, Barry A., Scharre, Douglas W., Kataki, Maria, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Gandy, Sam, Marenberg, Marjorie E., Rovner, Barry W., Pearlson, Godfrey, Anderson, Karen, Santulli, Robert B., Englert, Jessica, Williamson, Jeff D., Sink, Kaycee M., Watkins, Franklin, Ott, Brian R., Cohen, Ronald, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., and Mintzer, Jacobo

Subjects
mental disorders, Medicine and Health Sciences
Abstract

Objective:To investigate predictors of missing data in a longitudinal study of Alzheimer disease (AD).Methods:The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a clinic-based, multicenter, longitudinal study with blood, CSF, PET, and MRI scans repeatedly measured in 229 participants with normal cognition (NC), 397 with mild cognitive impairment (MCI), and 193 with mild AD during 2005–2007. We used univariate and multivariable logistic regression models to examine the associations between baseline demographic/clinical features and loss of biomarker follow-ups in ADNI.Results:CSF studies tended to recruit and retain patients with MCI with more AD-like features, including lower levels of baseline CSF Aβ42. Depression was the major predictor for MCI dropouts, while family history of AD kept more patients with AD enrolled in PET and MRI studies. Poor cognitive performance was associated with loss of follow-up in most biomarker studies, even among NC participants. The presence of vascular risk factors seemed more critical than cognitive function for predicting dropouts in AD.Conclusion:The missing data are not missing completely at random in ADNI and likely conditional on certain features in addition to cognitive function. Missing data predictors vary across biomarkers and even MCI and AD groups do not share the same missing data pattern. Understanding the missing data structure may help in the design of future longitudinal studies and clinical trials in AD.

Published
2012

31. Sex-dependent association of common variants of microcephaly genes with brain structure

Author

Rimol, Lars M., primary, Agartz, Ingrid, additional, Djurovic, Srdjan, additional, Brown, Andrew A., additional, Roddey, J. Cooper, additional, Kähler, Anna K., additional, Mattingsdal, Morten, additional, Athanasiu, Lavinia, additional, Joyner, Alexander H., additional, Schork, Nicholas J., additional, Halgren, Eric, additional, Sundet, Kjetil, additional, Melle, Ingrid, additional, Dale, Anders M., additional, Andreassen, Ole A., additional, Weiner, Michael, additional, Thal, Leon, additional, Petersen, Ronald, additional, Jack, Clifford R., additional, Jagust, William, additional, Trojanowki, John, additional, Toga, Arthur W., additional, Beckett, Laurel, additional, Green, Robert C., additional, Gamst, Anthony, additional, Potter, William Z., additional, Montine, Tom, additional, Anders, Dale, additional, Bernstein, Matthew, additional, Felmlee, Joel, additional, Fox, Nick, additional, Thompson, Paul, additional, Schuff, Norbert, additional, Alexander, Gene, additional, Bandy, Dan, additional, Koeppe, Robert A., additional, Foster, Norm, additional, Reiman, Eric M., additional, Chen, Kewei, additional, Shaw, Les, additional, Lee, Virginia M.-Y., additional, Korecka, Magdalena, additional, Crawford, Karen, additional, Neu, Scott, additional, Harvey, Danielle, additional, Kornak, John, additional, Kachaturian, Zaven, additional, Frank, Richard, additional, Snyder, Peter J., additional, Molchan, Susan, additional, Kaye, Jeffrey, additional, Vorobik, Remi, additional, Quinn, Joseph, additional, Schneider, Lon, additional, Pawluczyk, Sonia, additional, Spann, Bryan, additional, Fleisher, Adam S., additional, Vanderswag, Helen, additional, Heidebrink, Judith L., additional, Lord, Joanne L., additional, Johnson, Kris, additional, Doody, Rachelle S., additional, Villanueva-Meyer, Javier, additional, Chowdhury, Munir, additional, Stern, Yaakov, additional, Honig, Lawrence S., additional, Bell, Karen L., additional, Morris, John C., additional, Mintun, Mark A., additional, Schneider, Stacy, additional, Marson, Daniel, additional, Griffith, Randall, additional, Badger, Beverly, additional, Grossman, Hillel, additional, Tang, Cheuk, additional, Stern, Jessica, additional, deToledo-Morrell, Leyla, additional, Shah, Raj C., additional, Bach, Julie, additional, Duara, Ranjan, additional, Isaacson, Richard, additional, Strauman, Silvia, additional, Albert, Marilyn S., additional, Pedroso, Julia, additional, Toroney, Jaimie, additional, Rusinek, Henry, additional, de Leon, Mony J, additional, De Santi, Susan M, additional, Doraiswamy, P. Murali, additional, Petrella, Jeffrey R., additional, Aiello, Marilyn, additional, Clark, Christopher M., additional, Pham, Cassie, additional, Nunez, Jessica, additional, Smith, Charles D., additional, Given II, Curtis A., additional, Hardy, Peter, additional, DeKosky, Steven T., additional, Oakley, MaryAnn, additional, Simpson, Donna M., additional, Ismail, M. Saleem, additional, Porsteinsson, Anton, additional, McCallum, Colleen, additional, Cramer, Steven C., additional, Mulnard, Ruth A., additional, McAdams-Ortiz, Catherine, additional, Diaz-Arrastia, Ramon, additional, Martin-Cook, Kristen, additional, DeVous, Michael, additional, Levey, Allan I., additional, Lah, James J., additional, Cellar, Janet S., additional, Burns, Jeffrey M., additional, Anderson, Heather S., additional, Laubinger, Mary M., additional, Bartzokis, George, additional, Silverman, Daniel H.S., additional, Lu, Po H., additional, Fletcher, Rita, additional, Parfitt, Francine, additional, Johnson, Heather, additional, Farlow, Martin, additional, Herring, Scott, additional, Hake, Ann M., additional, van Dyck, Christopher H., additional, MacAvoy, Martha G., additional, Bifano, Laurel A., additional, Chertkow, Howard, additional, Bergman, Howard, additional, Hosein, Chris, additional, Black, Sandra, additional, Graham, Simon, additional, Caldwell, Curtis, additional, Feldman, Howard, additional, Assaly, Michele, additional, Hsiung, Ging-Yuek R., additional, Kertesz, Andrew, additional, Rogers, John, additional, Trost, Dick, additional, Bernick, Charles, additional, Gitelman, Darren, additional, Johnson, Nancy, additional, Mesulam, Marsel, additional, Sadowsky, Carl, additional, Villena, Teresa, additional, Mesner, Scott, additional, Aisen, Paul S., additional, Johnson, Kathleen B., additional, Behan, Kelly E., additional, Sperling, Reisa A., additional, Rentz, Dorene M., additional, Johnson, Keith A., additional, Rosen, Allyson, additional, Tinklenberg, Jared, additional, Ashford, Wes, additional, Sabbagh, Marwan, additional, Connor, Donald, additional, Obradov, Sanja, additional, Killiany, Ron, additional, Norbash, Alex, additional, Obisesan, Thomas O., additional, Jayam-Trouth, Annapurni, additional, Wang, Paul, additional, Auchus, Alexander P., additional, Huang, Juebin, additional, Friedland, Robert P., additional, DeCarli, Charles, additional, Fletcher, Evan, additional, Carmichael, Owen, additional, Kittur, Smita, additional, Mirje, Seema, additional, Johnson, Sterling C., additional, Borrie, Michael, additional, Lee, T-Y, additional, Asthana, Sanjay, additional, Carlsson, Cynthia M., additional, Potkin, Steven G., additional, Highum, Diane, additional, Preda, Adrian, additional, Nguyen, Dana, additional, Tariot, Pierre N., additional, Hendin, Barry A., additional, Scharre, Douglas W., additional, Kataki, Maria, additional, Beversdorf, David Q., additional, Zimmerman, Earl A., additional, Celmins, Dzintra, additional, Brown, Alice D., additional, Gandy, Sam, additional, Marenberg, Marjorie E., additional, Rovner, Barry W., additional, Pearlson, Godfrey, additional, Blank, Karen, additional, Anderson, Karen, additional, Saykin, Andrew J., additional, Santulli, Robert B., additional, Pare, Nadia, additional, Williamson, Jeff D., additional, Sink, Kaycee M., additional, Potter, Huntington, additional, Ashok Raj, B., additional, Giordano, Amy, additional, Ott, Brian R., additional, Wu, Chuang-Kuo, additional, Cohen, Ronald, additional, and Wilks, Kerri L., additional

Published
2009
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32. Hexanucleotide repeat expansions in C9ORF72in the spectrum of motor neuron diseases

Author

van Rheenen, Wouter, van Blitterswijk, Marka, Huisman, Mark H.B., Vlam, Lotte, Doormaal, Perry T.C. van, Seelen, Meinie, Medic, Jelena, Dooijes, Dennis, de Visser, Marianne, Kooi, Anneke J. van der, Raaphorst, Joost, Schelhaas, Helenius J., Pol, W. Ludo van der, Veldink, Jan H., Berg, Leonard H. van den, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Clifford, R. Jack, Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Saykin, Andrew J., Morris, John, Liu, Enchi, Montine, Tom, Gamst, Anthony, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Beckett, Laurel, Harvey, Danielle, Gamst, Anthony, Donohue, Michael, Kornak, John, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Mathis, Chet, Cairns, Nigel J., Taylor-Reinwald, Lisa, Shaw, Les, Lee, Virginia M.Y., Korecka, Magdalena, Crawford, Karen, Neu, Scott, Foroud, Tatiana M., Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J., Kaye, Jeffrey, Dolen, Sara, Quinn, Joseph, Schneider, Lon S., Pawluczyk, Sonia, Spann, Bryan M., Brewer, James, Vanderswag, Helen, Heidebrink, Judith L., Lord, Joanne L., Petersen, Ronald, Johnson, Kris, S. Doody, Rachelle, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Morris, John C., Mintun, Mark A., Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Mitsis, Effie, Romirowsky, Aliza, deToledo-Morrell, Leyla, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn, Onyike, Chiadi, Kielb, Stephanie, Rusinek, Henry, Leon, Mony J de, Glodzik, Lidia, Doraiswamy, P. Murali, Petrella, Jeffrey R., Arnold, Steven E., Karlawish, Jason H., Wolk, David, Smith, Charles D., Jicha, Greg, Hardy, Peter, Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Ismail, M. Saleem, Brand, Connie, Mulnard, Ruth A., Thai, Gaby, Mc-Adams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Swerdlow, Russell H., Bartzokis, George, Silverman, Daniel H.S., Lu, Po H., Apostolova, Liana, Graff-Radford, Neill R, Parfitt, Francine, Johnson, Heather, Farlow, Martin, Herring, Scott, Hake, Ann M., Dyck, Christopher H. van, Carson, Richard E., MacAvoy, Martha G., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Hsiung, Ging-Yuek Robin, Feldman, Howard, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Wu, Chuang-Kuo, Johnson, Nancy, Mesulam, Marsel, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A., Frey, Meghan, Johnson, Keith A., Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan, Belden, Christine, Jacobson, Sandra, Killiany, Ronald, Norbash, Alexander, Obisesan, Thomas O., Wolday, Saba, Bwayo, Salome K., Lerner, Alan, Hudson, Leon, Ogrocki, Paula, DeCarli, Charles, Fletcher, Evan, Carmichael, Owen, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Hendin, Barry A., Scharre, Douglas W., Kataki, Maria, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Saykin, Andrew J., Santulli, Robert B., Schwartz, Eben S., Williamson, Jeff D., Sink, Kaycee M., Watkins, Franklin, Ott, Brian R., Querfurth, Henry, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., Mintzer, Jacobo, Longmire, Crystal Flynn, Spicer, Kenneth, Kwon, Sun-Uck, Kim, Joon-Tae, Cho, Ki-Hyun, Shin, Dong-Ick, Ko, Yungchai, Lee, Soo Joo, Cha, Jae-Kwan, Kim, Yong-Jae, Shin, Dong-Jin, Jang, Hyuk, Choi, Nack-Cheon, Hong, Seok-Chang, Rha, Joung-Ho, Hong, Keun-Sik, Kim, Eung-Gyu, Choi, Jay Chol, Sohn, Sung-Il, Shin, Won Chul, HyukHeo, Sung, Chung, Kyung Cheon, Park, Jong-Ho, Lee, Jun Hong, Park, Jong-Moo, Park, Tai Hwan, Bae, Hee-Joon, Han, Moon-Ku, Kwon, Hyung-Min, Lee, Kyung Bok, Lee, Tae-Kyeong, Jeong, Dushin, Lee, Jun, Ashwal, Steve, deVeber, Gabrielle, Ferriero, Donna, Fullerton, Heather, Ichord, Rebecca, Kirkham, Fenella, Lynch, John K., O'Callaghan, Finbar, Pavlakis, Steve, Sebire, Guillaume, Willan, Andrew, Willan, Andrew, Sofronas, Marianne, Dlamini, Noma, Elbers, Jorina, Nowak-Göttl, Ulrike, Düring, Christine, Krümpel, Anne, Plumb, Patricia, Journeycake, Janna, van de Bruinhorst, Katrina, Gossett, Daniel, Chavez, Marta Isabel Hernandez, Monagle, Paul, MacKay, Mark, Barnes, Chris, Furmedge, Janine, Gordon, Anne, Benedict, Susan L., Bale, James F., Nielson, Denise, Abdalla, Abdalla, Chadehumbe, Madeline, Kabbouche, Marielle, Karti, Pooja, Phillips, Tonya, Friedman, Neil, Rizkallah, Elie, Zamel, Khaled, Wiznitzer, Max, Lidsky, Karen, Bernard, Timothy, Goldenberg, Neil A., Armstrong-Wells, Jennifer, Booth, Frances, Nash, Monica, Beslow, Lauren, Carpenter, Jessica, Chang, Taeun, Weinstein, Steven, Kan, Li, Smith, Robin, Maytal, Joseph, Sy-Kho, Rosemarie, Yager, Jerome Y., Massicotte, Patti, Ashwal, Steve, McClure, Chalmer, Bjornson, Bruce, Hukin, Juliet, Bucevska, Marija, Kent, Sheila, Riviello, James, Rivkin, Michael, Trenor, Cameron, Amlie-Lefond, Catherine, Whelan, Harry T., Ferriero, Donna, Fullerton, Heather, Fox, Christine, Pavlakis, Steve, Goodman, Sharon, Levinson, Kim, Kolk, Anneli, Laugesaar, Rael, Talvik, Tiina, Imam, Hussain, Thomas, Terrence, Golomb, Meredith, Kirton, Adam, Heyer, Geoffrey, Ganesan, Vijeya, Saengpattrachai, Montri, Crosswell, Hal, Mancuso, Ann, Tatishvili, Nana, Yeh, Ann, Humpherys, Peter, Abraham, Lisa, Alveal, Lucila Andrade, Ortiz, Manuel Arriaza, Altuna, Diana, Maxit, Clarisa, Gonzalez, Veronica, Alam, Muhammad, Buckley, David, Penney, Sharon, Jordan, Lori, Grabowski, Eric, Chan, Anthony, Deray, Marcel, Khatib, Zaid, Kovacevic, Gordana, Kosofsky, Barry, Leifer, Dana, Nass, Ruth, Wong, Virginia, Catsman, Coriene, El-Hakam, Lisa, Sebire, Guillaume, Cholette, Jill M., Narang, Shalu, Lerner, Norma B., Carpenter, Shannon, Bischoff, Kurt, Frei-Jones, Melissa, Masur, David, Epstein, Leon G, Bagiella, Emilia, Hinton, Veronica J., Gallentine, William, Rende, Elizabeth, Provenzale, James, Voyvodic, James, Song, Allen, Conklin, Terrie, O'Hara, Kathryn, Seinfeld, Syndi, Conry, Joan, Glauser, Tracy, Ayala, Jennifer, Facchini, Ronda, Sigalova, Maryana, Hannigan, James, Weiss, Erica, Mancini, Ann, Curran, John, Ahlm, Sarah, Renaldi, Julie, Umanzour, Diana K, Kim, Andrew, Hamidullah, Aaliyah, Litherland, Claire, Bonner, Melanie, Xu, Yuan, Van de Water, Virginia, Grasso, Susan, Kushner, David, Culbert, James, Bush, Brian J, Chandrasekaran, Sreedevi, Davis, Lori L, Rogers, Christiane, Sabo, Cynthia Shier, Wang, Helen, and Noebels, Jeffrey L

Abstract

To assess the frequency and phenotype of hexanucleotide repeat expansions in C9ORF72in a large cohort of patients of Dutch descent with familial (fALS) and sporadic (sALS) amyotrophic lateral sclerosis (ALS), progressive muscular atrophy (PMA), and primary lateral sclerosis (PLS).

Published
2012
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36. 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

37. A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly

Author

Ho, April J., Stein, Jason L., Hua, Xue, Lee, Suh, Hibar, Derrek P., Leow, Alex D., Dinov, Ivo D., Toga, Arthur W., Saykin, Andrew J., Shen, Li, Foroud, Tatiana, Pankratz, Nathan, Huentelman, Matthew J., Craig, David W., Gerber, Jill D., Allen, April N., Corneveaux, Jason J., Stephan, Dietrich A., DeCarli, Charles S., DeChairo, Bryan M., Potkin, Steven G., Jack, Clifford R., Weiner, Michael W., Raji, Cyrus A., Lopez, Oscar L., Becker, James T., Carmichael, Owen T., Thompson, Paul M., Weiner, Michael, Thal, Leon, Petersen, Ronald, Jagust, William, Trojanowki, John, Beckett, Laurel, Green, Robert C., Gamst, Anthony, Potter, William Z., Montine, Tom, Anders, Dale, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, Bandy, Dan, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Shaw, Les, Lee, Virginia M.-Y., Korecka, Magdalena, Crawford, Karen, Neu, Scott, Harvey, Danielle, Kornak, John, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J., Molchan, Susan, Kaye, Jeffrey, Vorobik, Remi, Quinn, Joseph, Schneider, Lon, Pawluczyk, Sonia, Spann, Bryan, Fleisher, Adam S., Vanderswag, Helen, Heidebrink, Judith L., Lord, Joanne L., Johnson, Kris, Doody, Rachelle S., Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Morris, John C., Mintun, Mark A., Schneider, Stacy, Marson, Daniel, Griffith, Randall, Badger, Beverly, Grossman, Hillel, Tang, Cheuk, Stern, Jessica, deToledo-Morrell, Leyla, Shah, Raj C., Bach, Julie, Duara, Ranjan, Isaacson, Richard, Strauman, Silvia, Albert, Marilyn S., Pedroso, Julia, Toroney, Jaimie, Rusinek, Henry, de Leon, Mony J, De Santi, Susan M, Doraiswamy, P. Murali, Petrella, Jeffrey R., Aiello, Marilyn, Clark, Christopher M., Pham, Cassie, Nunez, Jessica, Smith, Charles D., Given II, Curtis A., Hardy, Peter, DeKosky, Steven T., Oakley, MaryAnn, Simpson, Donna M., Ismail, M. Saleem, Porsteinsson, Anton, McCallum, Colleen, Cramer, Steven C., Mulnard, Ruth A., McAdams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Laubinger, Mary M., Bartzokis, George, Silverman, Daniel H.S., Lu, Po H., Fletcher, Rita, Parfitt, Francine, Johnson, Heather, Farlow, Martin, Herring, Scott, Hake, Ann M., van Dyck, Christopher H., MacAvoy, Martha G., Bifano, Laurel A., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Graham, Simon, Caldwell, Curtis, Feldman, Howard, Assaly, Michele, Hsiung, Ging-Yuek R., Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Gitelman, Darren, Johnson, Nancy, Mesulam, Marsel, Sadowsky, Carl, Villena, Teresa, Mesner, Scott, Aisen, Paul S., Johnson, Kathleen B., Behan, Kelly E., Sperling, Reisa A., Rentz, Dorene M., Johnson, Keith A., Rosen, Allyson, Tinklenberg, Jared, Ashford, Wes, Sabbagh, Marwan, Connor, Donald, Obradov, Sanja, Killiany, Ron, Norbash, Alex, Obisesan, Thomas O., Jayam-Trouth, Annapurni, Wang, Paul, Auchus, Alexander P., Huang, Juebin, Friedland, Robert P., DeCarli, Charles, Fletcher, Evan, Carmichael, Owen, Kittur, Smita, Mirje, Seema, Johnson, Sterling C., Borrie, Michael, Lee, T-Y, Asthana, Sanjay, Carlsson, Cynthia M., Highum, Diane, Preda, Adrian, Nguyen, Dana, Tariot, Pierre N., Hendin, Barry A., Scharre, Douglas W., Kataki, Maria, Beversdorf, David Q., Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Gandy, Sam, Marenberg, Marjorie E., Rovner, Barry W., Pearlson, Godfrey, Blank, Karen, Anderson, Karen, Santulli, Robert B., Pare, Nadia, Williamson, Jeff D., Sink, Kaycee M., Potter, Huntington, Ashok Raj, B., Giordano, Amy, Ott, Brian R., Wu, Chuang-Kuo, Cohen, Ronald, Wilks, Kerri L., Ho, April J., Stein, Jason L., Hua, Xue, Lee, Suh, Hibar, Derrek P., Leow, Alex D., Dinov, Ivo D., Toga, Arthur W., Saykin, Andrew J., Shen, Li, Foroud, Tatiana, Pankratz, Nathan, Huentelman, Matthew J., Craig, David W., Gerber, Jill D., Allen, April N., Corneveaux, Jason J., Stephan, Dietrich A., DeCarli, Charles S., DeChairo, Bryan M., Potkin, Steven G., Jack, Clifford R., Weiner, Michael W., Raji, Cyrus A., Lopez, Oscar L., Becker, James T., Carmichael, Owen T., Thompson, Paul M., Weiner, Michael, Thal, Leon, Petersen, Ronald, Jagust, William, Trojanowki, John, Beckett, Laurel, Green, Robert C., Gamst, Anthony, Potter, William Z., Montine, Tom, Anders, Dale, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, Bandy, Dan, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Shaw, Les, Lee, Virginia M.-Y., Korecka, Magdalena, Crawford, Karen, Neu, Scott, Harvey, Danielle, Kornak, John, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J., Molchan, Susan, Kaye, Jeffrey, Vorobik, Remi, Quinn, Joseph, Schneider, Lon, Pawluczyk, Sonia, Spann, Bryan, Fleisher, Adam S., Vanderswag, Helen, Heidebrink, Judith L., Lord, Joanne L., Johnson, Kris, Doody, Rachelle S., Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Morris, John C., Mintun, Mark A., Schneider, Stacy, Marson, Daniel, Griffith, Randall, Badger, Beverly, Grossman, Hillel, Tang, Cheuk, Stern, Jessica, deToledo-Morrell, Leyla, Shah, Raj C., Bach, Julie, Duara, Ranjan, Isaacson, Richard, Strauman, Silvia, Albert, Marilyn S., Pedroso, Julia, Toroney, Jaimie, Rusinek, Henry, de Leon, Mony J, De Santi, Susan M, Doraiswamy, P. Murali, Petrella, Jeffrey R., Aiello, Marilyn, Clark, Christopher M., Pham, Cassie, Nunez, Jessica, Smith, Charles D., Given II, Curtis A., Hardy, Peter, DeKosky, Steven T., Oakley, MaryAnn, Simpson, Donna M., Ismail, M. Saleem, Porsteinsson, Anton, McCallum, Colleen, Cramer, Steven C., Mulnard, Ruth A., McAdams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Laubinger, Mary M., Bartzokis, George, Silverman, Daniel H.S., Lu, Po H., Fletcher, Rita, Parfitt, Francine, Johnson, Heather, Farlow, Martin, Herring, Scott, Hake, Ann M., van Dyck, Christopher H., MacAvoy, Martha G., Bifano, Laurel A., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Graham, Simon, Caldwell, Curtis, Feldman, Howard, Assaly, Michele, Hsiung, Ging-Yuek R., Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Gitelman, Darren, Johnson, Nancy, Mesulam, Marsel, Sadowsky, Carl, Villena, Teresa, Mesner, Scott, Aisen, Paul S., Johnson, Kathleen B., Behan, Kelly E., Sperling, Reisa A., Rentz, Dorene M., Johnson, Keith A., Rosen, Allyson, Tinklenberg, Jared, Ashford, Wes, Sabbagh, Marwan, Connor, Donald, Obradov, Sanja, Killiany, Ron, Norbash, Alex, Obisesan, Thomas O., Jayam-Trouth, Annapurni, Wang, Paul, Auchus, Alexander P., Huang, Juebin, Friedland, Robert P., DeCarli, Charles, Fletcher, Evan, Carmichael, Owen, Kittur, Smita, Mirje, Seema, Johnson, Sterling C., Borrie, Michael, Lee, T-Y, Asthana, Sanjay, Carlsson, Cynthia M., Highum, Diane, Preda, Adrian, Nguyen, Dana, Tariot, Pierre N., Hendin, Barry A., Scharre, Douglas W., Kataki, Maria, Beversdorf, David Q., Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Gandy, Sam, Marenberg, Marjorie E., Rovner, Barry W., Pearlson, Godfrey, Blank, Karen, Anderson, Karen, Santulli, Robert B., Pare, Nadia, Williamson, Jeff D., Sink, Kaycee M., Potter, Huntington, Ashok Raj, B., Giordano, Amy, Ott, Brian R., Wu, Chuang-Kuo, Cohen, Ronald, and Wilks, Kerri L.

Abstract

A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.

38. Cerebellar Degeneration With Hodgkin Disease: An Immunological Study

Author

Trotter, John L., Hendin, Barry A., and Osterland, C. Kirk

Abstract

• A 21-year-old woman with subacute cerebellar degeneration was found to have Hodgkin lymphoma. Radiation therapy for the lymphoma halted the progression of her neurological disease. Using an immunofluorescent technique, we found the patient's serum to have antibodies to cerebellar Purkinje cells.

Published
1976
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39. Coccidioidal Meningitis Narcotic—Amphotericin B Intracisternal Therapy

Author

Yudell, Alan, Hendin, Barry A., Tamm, Harry S., and Guidry, James

Abstract

TO THE EDITOR. —We agree with Labadie and Hamilton1 that successful treatment of coccidioidal meningitis requires doses of amphotericin that exceed doses previously recommended. Since doses given less frequently than daily may not be fungistatic,2 we have attempted to treat patients every day with 1 mg of amphotericin B. In our experience, required dosages often exceed 80 mg. However, a significant obstacle to adequate therapy has been poor patient compliance because of the severe headaches and vomiting caused by intracisternal administration of amphotericin B.The use of a subcutaneous reservoir with access to the cisterna magna has facilitated therapy, in spite of the need for frequent reservoir revisions and complicating infections.2 This route of administration is more comfortable and results in fewer significant neurologic complications than does direct cisternal puncture. We abandoned lumbar intrathecal injections because of the almost universal appearance of permanent neurologic injury to the

Published
1988
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