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1. Lumbopelvic Muscle Mechanical Properties in Women with Multiple Sclerosis: A Cross-Sectional Case-Controlled Study

Author

Inés Cruz-Medel, María Ángeles Peña-Toledo, Francisco Alburquerque-Sendín, Daiana Priscila Rodrigues-de-Souza, Cristina Conde-Gavilán, Ana María Jover-Sánchez, Claudia Carmona-Medialdea, and Eduardo Agüera-Morales

Subjects
lumbar paravertebral muscles, MyotonPRO device, pelvic floor muscles, multiple sclerosis, Biology (General), QH301-705.5
Abstract

Background/Objectives: To compare the lumbopelvic muscle mechanical properties (MMPs) of women with and without multiple sclerosis (MS) and explore relationships between these properties and sociodemographic/clinical characteristics. Methods: This cross-sectional observational study included 22 women with MS and 22 age- and BMI-matched women without MS. MMPs (frequency, stiffness, decrement, relaxation, and creep) of pelvic floor and lumbar paravertebral muscles were assessed using a MyotonPRO device. Sociodemographic and clinical data related to pelvic floor health were also collected. Results: Women with MS showed significant differences in pelvic floor MMPs, including higher frequency (3.26 Hz; 95% CI [2.12, 4.41]), stiffness (90 N/m; 95% CI [55.09, 124.91]), and decrement (0.2; 95% CI [0.09, 0.31]), and lower relaxation (6.15 ms; 95% CI [8.26, 4.05]) and creep (0.24; 95% CI [0.34, 0.13]) compared to women without MS. For lumbar paravertebral muscles, differences were observed only on the right side, with lower frequency (2.15 Hz; 95% CI [0.28, 4.02]) and stiffness (62.17 N/m; 95% CI [10.7, 113.65]) in women with MS. Correlation patterns between MMPs and clinical characteristics differed by group, with moderate correlations found only in the MS group (e.g., EDSS: r = 0.57; p = 0.006; PFDI-20: r = 0.47; p = 0.026). Conclusions: Women with MS exhibit altered pelvic floor MMPs, characterized by reduced tone and stiffness and increased elasticity and viscoelasticity, while lumbar paravertebral differences are minimal. These findings highlight the need for objective MMP assessments in women with MS to guide preventive and therapeutic interventions.

Published
2024
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2. Comparative Study between the Diagnostic Effectiveness of Brain SPECT with [123I]Ioflupane and [123I]MIBG Scintigraphy in Multiple System Atrophy

Author

Javier Villena-Salinas, Simeón José Ortega-Lozano, Tomader Amrani-Raissouni, Eduardo Agüera-Morales, and Javier Caballero-Villarraso

Subjects
multiple system atrophy, dysautonomia, diagnostic accuracy, Ioflupane-123, meta-iodobenzylguanidine-123, Biology (General), QH301-705.5
Abstract

Background: Multiple system atrophy (MSA) is a neurodegenerative disease. It has a fast progression, so early diagnosis is decisive. Two functional imaging tests can be involved in its diagnosis: [123I]Ioflupane SPECT and [123I]MIBG scintigraphy. Our aim is to comparatively analyze the diagnostic performance of both techniques. Methods: 46 patients (24 males and 22 females) with MSA underwent [123I]Ioflupane SPECT and [123I]MIBG scintigraphy. In each of these techniques, qualitative assessment was compared with quantitative assessment. Results: SPECT visual assessment was positive in 93.5% of subjects (S = 95.24%; PPV = 93.02%). A cut-off of 1.363 was established for overall S/O index (S = 85.7%, E = 100%). Visual assessment of scintigraphy was positive in 73.1% (S = 78.57%, PPV = 94.29%). For the delayed heart/medistinum ratio (HMR) a cut-off of 1.43 (S = 85.3, E = 100%) was obtained. For each unit increase in delayed HMR, the suspicion of MSA increased by 1.58 (OR = 1.58, p < 0.05). The quantitative assessment showed an association with the visual assessment for each technique (p < 0.05). Conclusions: Both tests are useful in MSA diagnosis. Comparatively, we did not observe a clear superiority of either. Striatal and myocardial deterioration do not evolve in parallel. Qualitative assessment is crucial in both techniques, together with the support of quantitative analysis. Delayed HMR shows a direct relationship with the risk of MSA.

Published
2024
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3. New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab

Author

Inmaculada Toboso, Amalia Tejeda-Velarde, Roberto Alvarez-Lafuente, Rafael Arroyo, Harald Hegen, Florian Deisenhammer, Susana Sainz de la Maza, José C. Alvarez-Cermeño, Guillermo Izquierdo, Dolores Paramo, Pedro Oliva, Bonaventura Casanova, Eduardo Agüera-Morales, Diego Franciotta, Matteo Gastaldi, Oscar Fernández, Patricia Urbaneja, José M. Garcia-Dominguez, Fernando Romero, Alicia Laroni, Antonio Uccelli, Angel Perez-Sempere, Albert Saiz, Yolanda Blanco, Daniela Galimberti, Elio Scarpini, Carmen Espejo, Xavier Montalban, Ludwig Rasche, Friedemann Paul, Inés González, Elena Álvarez, Cristina Ramo, Ana B. Caminero, Yolanda Aladro, Carmen Calles, Pablo Eguía, Antonio Belenguer-Benavides, Lluis Ramió-Torrentà, Ester Quintana, José E. Martínez-Rodríguez, Agustín Oterino, Carlos López de Silanes, Luis I. Casanova, Lamberto Landete, Jette Frederiksen, Gabriel Bsteh, Patricia Mulero, Manuel Comabella, Miguel A. Hernández, Mercedes Espiño, José M. Prieto, Domingo Pérez, María Otano, Francisco Padilla, Juan A. García-Merino, Laura Navarro, Alfonso Muriel, Lucienne Costa Frossard, and Luisa M. Villar

Subjects
multiple sclerosis, demyelinating diseases, biomarkers, natalizumab, progressive multifocal leucoencephalopathy, disease modifying treatments, Neurology. Diseases of the nervous system, RC346-429
Abstract

Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression.Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from 0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from

Published
2020
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5. Effectiveness and safety of PCSK9 inhibitors in real-world clinical practice. An observational multicentre study. The IRIS-PCSK9I study

Author

Rodrigo Milán Pinilla, María Magdalena Carrillo Bailén, Marina Blanco-Ruiz, María Josefa Álvarez Soria, Belén Sánchez Rodríguez, Patricia Martínez-Sánchez, Laura Amaya-Pascasio, Roberto Valverde Moyano, Irene Pérez Ortega, María Victoria Mejías Olmedo, Pablo González Bustos, Javier Fernández Pérez, Purificación Sánchez López, Reyes de Torres Chacón, Eduardo Agüera Morales, Manuel Payán Ortiz, Luis Andrade Zumárraga, Antonio Arjona-Padillo, Alba María Castillo Fernández, Cristina Del Toro Pérez, Beatriz Hidalgo Martín, and Ricardo Roa Chamorro

Subjects
medicine.medical_specialty, Statins intolerance, business.industry, PCSK9, Retrospective cohort study, Cardiovascular disease, Evolocumab, Clinical trial, Ezetimibe, Internal medicine, PCSK9i, RC666-701, Internal Medicine, Medicine, Hypercholesterolemia familiar, Diseases of the circulatory (Cardiovascular) system, Observational study, Cardiology and Cardiovascular Medicine, business, Mace, Alirocumab, medicine.drug
Abstract

Background and aims: The benefits of the PCSK9 inhibitors, alirocumab and evolocumab, in lowering LDL-cholesterol and preventing major adverse cardiac events (MACE) have been demonstrated in pivotal clinical trials. However, few studies of routine clinical practice have been conducted to analyse and compare the efficacy and safety of the two drugs. Methods: Retrospective observational study of patients treated with a PCSK9 inhibitor in five hospitals in Andalusia (southern Spain). Baseline demographic and clinical data, LDL-cholesterol levels and the occurrence of MACEs during the follow-up period were recorded. Results: A total of 141 patients were included in the study: 90 were treated with alirocumab and 51 with evolocumab. The patients’ mean age (IQR) was 58 (11) years and 58 (41%) were women. The most frequent concomitant medications were statins, 94 (66.7%), followed by antiplatelet therapy (66%) and ezetimibe (65.2%). The median (IQR) follow-up period was 18 (18) months, with 18 (24) for alirocumab and 11 (18) for evolocumab. At the six-month follow-up visit, LDL-cholesterol values had decreased to pre-treatment levels and remained significantly decreased (p

Published
2021

6. Safety, tolerability, and activity of mesenchymal stem cells versus placebo in multiple sclerosis (MESEMS): a phase 2, randomised, double-blind crossover trial

Author

Antonio Uccelli, Alice Laroni, Rehiana Ali, Mario Alberto Battaglia, Morten Blinkenberg, Lou Brundin, Michel Clanet, Oscar Fernandez, James Marriott, Paolo Muraro, Seyed Massood Nabavi, Roberto S Oliveri, Ernst Radue, Cristina Ramo Tello, Irene Schiavetti, Johann Sellner, Per Soelberg Sorensen, Maria Pia Sormani, Jens Thomas Wuerfel, Mark S Freedman, Naser Aghdami, Eduardo Agüera-Morales, David Allan, Leila Arab, Mario Battaglia, Isabelle Berry, Bruno Bonetti, Chiara Capelli, Lucio Castellan, Maria Cellerino, Maria Teresa Cencioni, Giancarlo Comi, David Courtman, Francesco Dazzi, Anne Fischer-Nielsen, Victoria Fernandez, Mark S. Freedman, Roberto Furlan, Mario Gimona, Francesca Gualandi, Qingdong Guan, Ellen Iacobaeus, Matilde Inglese, Martino Introna, Guillermo Izquierdo, Shahedeh Karimi, Katarina Le Blanc, Sandra Loaiza, Shahrukh Mallik, Stephen Marley, Ruth Ann Marrie, James Marriot, Gianvito Martino, David Miller, Paolo A. Muraro, Richard Nicholas, Giovanni Orengo, Renuka Palanicawande, Matteo Pardini, Ernst W Radue, Carolina Rush, Luc Sensebe, Dirk Strunk, David Szwajcer, and Claire Thalamas

Subjects
Adult, medicine.medical_specialty, Multiple Sclerosis, Adolescent, Placebo, Young Adult, Double-Blind Method, Internal medicine, Clinical endpoint, Humans, Medicine, Adverse effect, Cross-Over Studies, Expanded Disability Status Scale, business.industry, Surrogate endpoint, Multiple sclerosis, Brain, Mesenchymal Stem Cells, Middle Aged, medicine.disease, Crossover study, Malformations of Cortical Development, Tolerability, Neurology (clinical), business
Abstract

Summary Background Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells, have been proposed as a promising therapeutic option for people with multiple sclerosis on the basis of their immunomodulatory and neuroprotective properties. The MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) study was devised to evaluate the safety, tolerability, and activity of autologous MSCs derived from bone marrow and infused intravenously in patients with active multiple sclerosis. Methods MESEMS is a randomised phase 2 trial done at 15 sites in nine countries. Patients (aged 18–50 years) with active relapsing-remitting or progressive multiple sclerosis were included if they had a disease duration of 2–15 years since onset of multiple sclerosis and an Expanded Disability Status Scale score of 2·5–6·5. Patients were randomly assigned (1:1), according to a crossover design, to receive a single intravenous dose of autologous bone marrow-derived MSCs followed by placebo at week 24, or to receive placebo followed by autologous MSCs at week 24, with a follow-up visit at week 48. Primary objectives were to test safety and activity of MSC treatment. The primary safety endpoint was to assess the number and severity of adverse events within each treatment arm. The primary efficacy endpoint was the number of gadolinium-enhancing lesions (GELs) counted over week 4, 12, and 24 compared between treatment groups. The primary efficacy endpoint was assessed in the full analyis set, after all participants completed the week 24 visit. Efficacy endpoints were evaluated using a predefined statistical testing procedure. Safety was monitored throughout the study by recording vital signs and adverse events at each visit. Findings From July 16, 2012, until July 31, 2019, 144 patients were randomly assigned to first receive early intravenous infusion of autologous bone marrow-derived MSCs (n=69) or placebo (n=75). MSC treatment did not meet the primary endpoint of efficacy on the total number of GELs accumulated from baseline to week 24 (rate ratio [RR] 0·94, 95% CI 0·58–1·50; p=0·78). 213 adverse events were recorded, similarly distributed between groups (93 cases recorded in 35 [51%] of 69 patients treated first with MSCs vs 120 cases in 42 [56%] of 75 patients infused first with placebo). The most frequent adverse events reported were infection and infestations, with a total of 54 (25%) of 213 adverse events (18 [19%] of 93 in the early-MSC group and 36 [30%] of 120 in the delayed-MSC group). Nine serious adverse events were reported in seven patients treated with placebo versus none in the MSC group. All serious adverse events were considered to be unrelated to the treatment infusion. No deaths were reported during the study. Interpretation Bone marrow-derived MSC treatment was safe and well tolerated but did not show an effect on GELs, an MRI surrogate marker of acute inflammation, in patients with active forms of multiple sclerosis, at week 24. Thus, this study does not support the use of bone marrow-derived MSCs to treat active multiple sclerosis. Further studies should address the effect of MSCs on parameters related to tissue repair. Funding Fondazione Italiana Sclerosi Multipla (FISM), the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), and the Multiple Sclerosis International Federation (MSIF) for centralised activities. Individual trials participating in the MESEMS network are funded by the following agencies: FISM and Compagnia di San Paolo (Italy); The Danish Multiple Sclerosis Society, The Toyota Foundation, and Danish Blood Donors’ Research Foundation (Denmark); the Spanish Health Research Institute Carlos 3 and the Andalusian Public Foundation Progreso y Salud (Spain); the Royan Institute for Stem Cell Biology and Technology (Iran); the Spinal Cord Injury and Tissue Regeneration Centre Salzburg, Paracelsus Medical University, and Salzburg (Austria); the Fondation pour l’aide a la recherche sur la sclerose en plaques (ARSEP), French Muscular Dystrophy Association (AFM)-Telethon (France); the UK Multiple Sclerosis Society and the UK Stem Cell Foundation (UK); and the Multiple Sclerosis Society of Canada and The Multiple Sclerosis Scientific Research Foundation and Research Manitoba (Canada).

Published
2021
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7. Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY)

Author

Diego Cadavid, Michelle Mellion, Raymond Hupperts, Keith R Edwards, Peter A Calabresi, Jelena Drulović, Gavin Giovannoni, Hans-Peter Hartung, Douglas L Arnold, Elizabeth Fisher, Richard Rudick, Sha Mi, Yi Chai, Jie Li, Yiwei Zhang, Wenting Cheng, Lei Xu, Bing Zhu, Susan M Green, Ih Chang, Aaron Deykin, Sarah I Sheikh, Eduardo Agüera Morales, Abdullatif Al Khedr, Radek Ampapa, Rafael Arroyo, Martin Belkin, Robert Bonek, Alexey Boyko, Ruggero Capra, Diego Centonze, Pierre Clavelou, Marc Debouverie, Jelena Drulovic, Keith Edwards, Nikos Evangelou, Evgeniy Evdoshenko, Oscar Fernández, Victoria Fernández Sánchez, Mark Freedman, Steven Freedman, Waldemar Fryze, Antonio Garcia-Merino, Mira Gavric-Kezic, Angel Ghezzi, Olivier Gout, Luigi Grimaldi, Barry Hendin, Hanka Hertmanowska, Rogier Hintzen, Pavel Hradilek, Jan Ilkowski, Evelina Ivashinenkova, Guillermo Izquierdo, Francois Jacques, Gabor Jakab, Farit Khabirov, Gabriela Klodowska-Duda, Samuel Komoly, Smiljana Kostic, Ivana Kovarova, Marcelo Kremenchuzky, Christopher Laganke, Yves LaPierre, Maciej Maciejowski, Francois Grand Maison, Girolama Alessandra Marfia, Sergio Martínez Yélamos, Eva Meluzinova, Xavier Montalban, Ronald Murray, Robert Naismith, Scott Newsome, Viet Nguyen, Delia Oreja, Gabriel Pardo, Elena Pasechnik, Francesco Patti, Andrzej Potemkowski, Semen Prokopenko, Peiqing Qian, Alfredo Rodríguez-Antigüedad, Howard Rossman, Csilla Rozsa, Fernando Sánchez López, Krzysztof Selmaj, Eli Silber, Adam Stepien, Anna Stepniewska, Maciej Swiat, Gordana Toncev, Ayman Tourbah, Tatyana Trushnikova, Antonio Uccelli, Marta Vachova, Martin Valis, Laszlo Vecsei, Sandrine Wiertlewski, Mauro Zaffaroni, Tomasz Zielinski, Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), and RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience

Subjects
0301 basic medicine, EXPRESSION, medicine.medical_specialty, Paced Auditory Serial Addition Test, Phases of clinical research, Placebo, Settore MED/26, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, SPINAL-CORD REMYELINATION, 10. No inequality, Adverse effect, Expanded Disability Status Scale, medicine.diagnostic_test, business.industry, Multiple sclerosis, CENTRAL-NERVOUS-SYSTEM, Oligodendrocyte differentiation, medicine.disease, 3. Good health, 030104 developmental biology, Neurology (clinical), CNS, business, OLIGODENDROCYTE DIFFERENTIATION, 030217 neurology & neurosurgery, LINGO-1
Abstract

Summary Background Opicinumab is a human monoclonal antibody against LINGO-1, an inhibitor of oligodendrocyte differentiation and axonal regeneration. Previous findings suggested that opicinumab treatment might enhance remyelination in patients with CNS demyelinating diseases. We aimed to assess the safety and efficacy of opicinumab in patients with relapsing multiple sclerosis. Methods We did a randomised, double-blind, placebo-controlled, dose-ranging, phase 2 study (SYNERGY) at 72 sites in 12 countries. Participants (aged 18–58 years) with relapsing multiple sclerosis (relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis with relapses) were randomised in a 1:2:2:2:2 ratio by an interactive voice and web response system to opicinumab 3 mg/kg, 10 mg/kg, 30 mg/kg, or 100 mg/kg, or placebo. An identical volume of study drug was administered intravenously once every 4 weeks. All participants self-administered intramuscular interferon beta-1a as background anti-inflammatory treatment once a week. The primary endpoint was the percentage of participants achieving confirmed disability improvement over 72 weeks, which was a multicomponent endpoint measured by the Expanded Disability Status Scale, the Timed 25-Foot Walk, the Nine-Hole Peg Test, and the 3 s Paced Auditory Serial Addition Test. The primary endpoint was analysed under intention-to-treat principles. This study is registered at ClinicalTrials.gov , number NCT01864148 . Findings Between Aug 13, 2013, and July 31, 2014, 419 patients were enrolled and randomly assigned either placebo (n=93) or opicinumab 3 mg/kg (n=45), 10 mg/kg (n=95), 30 mg/kg (n=94; one patient did not receive the assigned treatment), or 100 mg/kg (n=92). The last patient visit was on March 29, 2016. Confirmed disability improvement over 72 weeks was seen in 45 (49%) of 91 patients assigned to placebo, 21 (47%) of 45 assigned to opicinumab 3 mg/kg, 59 (63%) of 94 assigned to opicinumab 10 mg/kg, 59 (65%) of 91 assigned to opicinumab 30 mg/kg, and 36 (40%) of 91 assigned to opicinumab 100 mg/kg. A linear dose-response in the probability of confirmed disability improvement was not seen (linear trend test p=0·89). Adverse events occurred in 79 (85%) patients assigned placebo and in 275 (85%) assigned any dose of opicinumab. The most common adverse events of any grade in patients assigned any dose of opicinumab included influenza-like illness (140 [43%] with any dose of opicinumab vs 37 [40%] with placebo), multiple sclerosis relapses (117 [36%] vs 30 [32%]), and headache (51 [16%] vs 23 [25%]). Serious adverse events reported as related to treatment were urinary tract infection in one (1%) participant in the the placebo group, suicidal ideation and intentional overdose in one (1%) participant in the 30 mg/kg opicinumab group, bipolar disorder in one (1%) participant in the 100 mg/kg opicinumab group, and hypersensitivity in four (4%) participants in the 100 mg/kg opicinumab group. One patient in the opicinumab 30 mg/kg group died during the study due to a traffic accident, which was not considered related to study treatment. Interpretation Our findings did not show a significant dose-linear improvement in disability compared with placebo in patients with relapsing multiple sclerosis. Further studies are needed to investigate whether some subpopulations identified in the study might benefit from opicinumab treatment at an optimum dose. Funding Biogen.

Published
2019
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8. Benefits of eculizumab in AQP4+ neuromyelitis optica spectrum disorder: Subgroup analyses of the randomized controlled phase 3 PREVENT trial

Author

Jacqueline Palace, Dean M. Wingerchuk, Kazuo Fujihara, Achim Berthele, Celia Oreja-Guevara, Ho Jin Kim, Ichiro Nakashima, Michael Levy, Murat Terzi, Natalia Totolyan, Shanthi Viswanathan, Kai-Chen Wang, Amy Pace, Marcus Yountz, Larisa Miller, Róisín Armstrong, Sean Pittock, Daniel Julio Muñoz, Jorge David Amor, Carolina Bocchiardo, Julieta Iourno Danielle, Alfredo Laffue, Carolina Daniela Diaz Obregon, Maria Fernanda Paez, Roberto Martin Perez, Viviana Ana Maria Rocchi, Loreley Deborah Teijeiro, Jesica Gómez, Andres Maria Villa, Florencia Aguirre, Victoria Carla Fernández, Ramon F. Goicoechea, Luciana Melamud, Ana Stillman, Mariana de Virgiliis, Fatima Pagani Cassara, Marta Cordoba, Maria Teresa Gutierrez, Mariana Ingolotti, Natalia Larripa, Anahi Lupinacci, Josefina Arroyo, Alejandra Romano, Mariana Foa Torres, Carlos Héctor Ballario, Ana Elisa Chiesa, Hernán Gustavo Gómez, Hernán Gabriel Lattini, Carolina Natalia Mainella, Gisel Edith Bolner, María Soledad Eschoyez, Simon Andrew Broadley, Saman Heshmat, Arman Sabet, Andrew Swayne, Susan Freeman, Sofia Jimenez Sanchez, Neil Shuey, Linda Dalic, Ann French, Guru Kuma, Joshua Laing, Lai Yin Law, Jennifer MacIntyre, Andrew Neal, Christopher Plummer, Prashanth Ramachandran, Leslie Sedal, Ian Wilson, Antony Winkel, Wenwen Zhang, Tina Chen, Rani Watts, Michael Barnett, Joshua Barton, Heidi Beadnall, Justin Garber, Todd Andrew Hardy, Benjamin Trewin, Marinda Taha, Deleni Walters, Federico Arturo Silva Sieger, Nhora Patricia Ruiz Alfonso, Anna Maria Pinzon Camacho, Alexander Pabón Moreno, Jorge Armando Castellanos Prad, Adriana Paola Duarte Rueda, Tatiana Castillo, Karol Melissa Castillo Gonzalez, Martha Yolanda Moreno Pico, Judith Castill, Mario Habek, Ivan Adamec, Barbara Barun, Luka Crnosija, Tereza Gabelic, Petra Nytrova, Eva Krasulova, Jana Pavlickova, Michaela Tyblova, Jana Zubkova, Thor Petersen, Gro Helen Dale, Peter Vestergaard Rasmussen, Morten Stilund, Kristina Bacher Svendsen, Vivi Brandt, Nicolas Collongues, Marie-Celine Fleury, Laurent Kremer, Sandrine Bendele, Valérie Neff, Ricarda Diem, Michael Platten, Anne Berberich, Jonabelle Jansen, Hannah Jaschoneck, Brigitte Wildemann, Ursula Aures, Tanja Brandenburger, Tanja Haut, Maria-Lourdes Treceno Fernández, Lilian Aly, Kirsten Brinkhoff, Dorothea Buck, Daniel Golkowski, Mirjam Hermisson, Muna-Miriam Hoshi, Miriam Kaminski, Markus Christian Kowarik, Helena Kronsbein, Klaus Lehmann-Horn, Viola Maria Pongratz, Andreas Schweiker, Lisa-Ann Leddy, Silvia Mueller, Kim Obergfell, Marion Wanka, Uwe Klaus Zettl, Jan Klinke, Micha Loebermann, Stefanie Meister, Florian Rimmele, Alexander Winkelmann, Ina Schroeder, Alexander Yuk-Lun Lau, Lisa Wing-Chi Au, Florence Sin-Ying Fan, Vincent Hing-Lung Ip, Karen Ka-Yan Ma, Sze-Ho Ma, Vincent Chung-Tong Mok, Cheryl Chung-Kwan Au, Pauline Wing-Lam Kwan, Francesco Patti, Andrea Salvatore Caramma, Clara Grazia Chisari, Salvatore Lo Fermo, Silvia Messina, Maria Projetto, Cinzia Caserta, Alessandro Filla, Teresa Costabile, Chiara Pane, Francesco Sacca, Angela Marsili, Giorgia Puorro, Roberto Bergamaschi, Eliana Berra, Giulia Mallucci, Cinzia Fattore, Claudio Gasperini, Simonetta Galgani, Shalom Haggiag, Serena Ruggieri, Claudio Vento, Esmeralda Maria Quartuccio, Carlo Pozzilli, Valeria Teresa Barletta, Giovanna Borriello, Laura De Giglio, Fabiana Marinelli, Miriam Tasillo, Alessandra Amadori, Mariano Fischetti, Flavia Gurreri, Masahiro Mori, Hiroki Masuda, Ryohei Ohtani, Yukari Sekiguchi, Tomohiko Uchida, Akiyuki Uzawa, Hiromi Ito, Emi Kabasawa, Yoko Kaneko, Takuya Matsushita, Dai Matsuse, Hiroyuki Murai, Shintaro Hayashi, Katsuhisa Masak, Hidenori Ogata, Koji Shinoda, Taira Uehara, Mitsuru Watanabe, Hiroo Yamaguchi, Ryo Yamasaki, Tomomi Yonekawa, Maki Jingu, Makiko Nagano, Yumiko Nakamura, Yoshiko Sano, Manabu Araki, Youwei Lin, Madoka Mori, Yohei Mukai, Terunori Sano, Wakiro Sato, Naoya Gogun, Yuriko Maeda, Asami Nishimoto, Sachiko Tsukamoto, Ritsuko Yanagi, Takahiko Saida, Shinichi Nakamura, Tetsuya Nasu, Kyoko Saida, Yuko Shikata, Yoshimi Kodani, Megumi Saeki, Yukako Sawada, Hiroo Yoshikawa, Takashi Kimura, Masamitsu Nishi, Shun Sakamoto, Shinichiro Ukon, Shohei Watanabe, Saori Ebisuya, Nami Kimura, Manami Matsuura, Yukie Morisaki, Yoshiko Muroi, Kuniko Onishi, Ikuko Oshima, Yuki Washino, Tomomi Yamashita, Tatsuro Misu, Kimihiko Kaneko, Masaaki Kato, Hiroshi Kuroda, Kazuhiro Kurosawa, Shuhei Nishiyama, Hirohiko Ono, Yoshiki Takai, Keiko Abe, Hitomi Hoshi, Mari Jinushi, Azusa Oyama, Motonari Sakuma, Yuko Sawada, Satoru Ishibashi, Takanori Yokota, Yoichiro Nishida, Kokoro Ozaki, Nobuo Sanjo, Nozomu Sato, Fuki Denno, Haruko Hiraki, Yumi Matsubara, Takashi Kanda, Masaaki Abe, Masaya Honda, Motoharu Kawai, Michiaki Koga, Toshihiko Maeda, Junichi Ogasawara, Masatoshi Omoto, Yasuteru Sano, Ryota Sato, Fumitaka Shimizu, Hideki Arima, Sachie Fukui, Yoshiko Ishikawa, Tomoko Koyama, Shigemi Shimose, Hirokazu Shinozaki, Masanori Watanabe, Sachi Yasuda, Chieko Yoshiwaka, Suffian Adenan, Mohd Azman M Aris, Ahmad Shahir bin Mawardi, Muhammad Al Hafiz Adnan, Nanthini Munusamy, Siti Nur Omaira Razali, Punitha Somasundram, Jae Won Hyun, In Hye Jeong, Su-Hyun Kim, Hyun-June Shin, Ji Sung Yoo, HyunMin Jang, AeRan Joung, Byung-Jo Kim, Seol-Hee Baek, Jung Bin Kim, Yoo Hwan Kim, Yong Seo Koo, Chan Nyoung Lee, Hung Youl Seok, Jinhee Hwang, Sung Min Kim, So Hyun Ahn, Kyomin Choi, Seok-Jin Choi, Jun-Soon Kim, Young Nam Kwon, Je-Young Shin, Hyeonju Kwon, Byoung Joon Kim, Eun Bin Cho, Hye-Jin Cho, Misong Choi, DongSun Kim, Ju Hyeon Kim, SeungJu Ki, Hye Lim Lee, Kwang-Ho Lee, Ju-Hong Min, Ji-Hyung Park, Jinmyoung Seok, Eunhwa Choi, Sang Ae Park, Seung Min Kim, Ha-Neul Jeong, Bong Jeongbin, Jin Woo Jung, Seung Woo Kim, Yool-hee Kim, Hyung Seok Lee, Ha Young Shin, Yeon Jung, Min Jung Kim, Nou Ri Lee, MiJu Shin, Farit A Khabirov, Lyudmila Averyanova, Natalya Babicheva, Eugenii Granatov, Sergey Kazarov, Timur Khaybullin, Alexander Rogozhin, Dmitry V Pokhabov, Vladislav Abramov, Anastasia Amelina, Yulia Nesteroca, Tatyana Bozhenkina, Aleksey N Boyko, Elena G Demyan, Inessa Khoroshilova, Mikhail Melnikov, Ekaterina V Popova, Svetlana N Sharanova, Sergey G Shchur, Denis V Sazonov, Larisa Babenko, Elena Bayandina, Asya Yarmoschuk, Victor A Baliazin, Elena Baliazina, Elena Budaeva, Irina Chernikova, Zoya Goncharova, Vladimir Krasnov, Marina Myatleva, Olga V. Rodionova, Iuliana Samulyzhko, Alla A. Timofeeva, Sabas Boyero Duran, Maria Mar Mendibe Bilbao, Irene Diaz Cuervo, Jose Maria Losada Domingo, Amaia Gonzalez Eizaguirre, Jose Eulalio Barcena Llona, Roberto Valverde Moyano, Carmen Bahamonde, Fernando Sanchez Lopez, Raquel Pinar Morales, Eduardo Agüera Morales, Carmen Bahamonde Roman, Juan Jose Ochoa Sepulveda, Maria del Carmen Blanco Valero, Nazaret Pelaez Viña, Cristina Conde Gavilan, Ana Maria Jover Sanchez, Sara Vila Bedmar, Nuria Gonzalez Garcia, Aida Orviz Garcia, Ines Gonzalez-Suarez, Elena Miñano Guillamon, Miguel Kawiorski, Elena Guerra Schulz, Alba Garcia Alonso, Francisco Jesus Lopez Perez, Marta Palacios Sarmiento, Guillermo Izquierdo Ayuso, Guillermo Navarro Mascarell, Cristina Paramo Camino, Asuncion Varas Garcia, Yaiza Montserrat Mendoza, Veronica Ines Vargas Muñoz, Patricia Torres Tonda, Ching-Piao Tsai, Jiu-Haw Yin, Mei-Jung Chen, Shan-Ni Li, Fei-Ti Wang, Suwat Srisuwannanukorn, Thanatat Boonmongkol, Duangporn Borisutbuathip, Duangkamol Singwicha, Krittika Siritanan, Chidchanoke Thearapati, Kwanmuang Sornda, Metha Apiwattanakul, Saharat Aungsumart, Narupat Suanprasert, Kaona Suksuchano, Nittaya Parkinsee, Kongkiat Kulkantrakorn, Praween Lolekha, Artit Potigumjon, Puchit Sukphulloprat, Dararat Suksasunee, Chankawee Komaratat, Sunattana Luangtong, Arkhom Arayawichanont, Phanpaphon Konpan, Nathapol Riablershirun, Thaddao Wiroteurairuang, Panadda Jantaweesirirat, Aslı Kurne, Irem Erkent, Ebru Bekircan Kurt, Ezgi Saylam, Yagmur Caliskan, Gulsah Orsel, Yahya Celik, Canan Celebi, Aslan Tekatas, Tugce Banbal, Gulsen Akman Demir, Burcu Altunrende, Zeliha Matur, Baris Topcular, Tules Elmas, Aysenur Gulo, Selin Ozdemir, Cansu Ozkoklesen, Mahinur Ozturk, Mertkan Yanik, Elif Yildirim, Melih Tutuncu, Ayse Altintas, Abdulsamet Cam, Ayse Deniz Elmali, Sabahattin Saip, Aksel Siva, Uygur Tanrıverdi, Ugur Uygunoglu, Sinem Caliskan, Pinar Gulo, Esra Kozig, Sakine Sakiz, Ihsan Sukru Sengun, Egemen Idiman, Rahmi Tumay Ala, Duygu Arslan, Utku Bulut, Yasemin Karakaptan, Derya Kaya, Zaur Mehdiyev, Bengu Balkan, Berfu Kuku, Mujgan Ozhun, Celal Tuga, Muzeyyen Ugur, Husnu Efendi, Sena Destan Bunul, Hakan Cavus, Yunus Emre Gorke, Ayse Kutlu, Seda Ozturk, Cansu Egilmez Sarikaya, Gulsah Becerikli, Cansu Semiz, Ozlem Tun, Sehriban Ayer, Musa Kazim Onar, Mehlika Berra Ozberk, Sedat Sen, Tugce Kirbas Cavdar, Adife Veske, Cavit Boz, Didem Altiparmak, Cigdem Ozen Aydin, Sibel Gazioglu, Duygu Bekircan, Anu Jacob, Heike Arndt, Liene Elsone, Shahd Hassan Mahmoud Hamid, Daniel Hugh Whittam, Martin Wilson, Imelda O'Brien, Maria Isabel da Silva Leite, Pedro Maria Rodriguez Cruz, Damian Robert Jenkins, George Tackley, Ana Cavey, Rosie Everett, Joy Hodder, Abigail Koelewyn, Ellen Mowry, Walter Royal, Robert Shin, Christopher Bever, Daniel Harrison, Horea Rus, Wei Zheng, Karen Callison, Kerry Naunton, Benjamin M Frishberg, Andrew M Blumenfeld, Andrew Inocelda, Kalyani Korabathina, Michael Lobatz, Melissa M Mortin, Irene J Oh, Jay H Rosenberg, Mark Sadoff, Gregory A Sahagian, Anchi Wang, Yasmin Camberos, Guadalupe Sanchez, Estela Soto, Jacqueline A Nicholas, Aaron Boster, Geoffrey Eubank, Katy Groezinger, Meghan Lauf, Annette F Okai, Rashedul Hasan, Chaouki Khoury, Victoria Stokes, Stacey Clardy, Melissa Cortez, John Greenlee, John Rose, Mateo Paz Soldan, Amanda Emett, Lawanda Esquibel, Lilly Fagatele, Ka-Ho Wong, James C Stevens, Thomas M Banas, Marlene C Bultemeyer, Andrea Haller, Natalie Manalo, Keri Aeschliman, Debi Kocks, Michael Racke, Aaron Lee Boster, Michelle Bowman, Jaime Imitola, Yasushi Kisanuki, Misty Green, Stephanie Scarberry, Sharon G Lynch, Heather S Anderson, Gary S Gronseth, Nancy E Hammond, Yasir N Jassam, Manoj K Mittal, Muhammed M Nashatizadeh, Nicholas Levine, Lisa Schmidt, Jill Sibley, Vonda Whitley, James Winkley, Timothy Coleman, Gregory Cooper, Stephanie Sheffield, Keri Turner, Dana Galloway, Robert S Tillett, Geeta A Ganesh, Brian M Plato, Tad D Seifert, Diana Godwin, Deborah Lockridge, Kottil W Rammohan, William A Sheremata, Silvia Delgado, Jose Gonzalez, Alexis Lizarraga, Janice Maldonado, Melissa Ortega, Leticia Tornes, Yanet Babcock, Osmara Cailam, Yesica Campos, Irlisse Couvertier, Bettina Daneri, Jeremy Deni, Jeffrey Hernandez, Tatiana Jaramillo, Tenita Morris, Daniel Nobel, Anjelis Oliveira, Reshma Richardson, Gloria Rodriguez, Ana Romero, Carlos Sandova, Ruta Sawant, Lissett Tueros, Eric S Zetka, Chao Zheng, Daniel H Jacobs, Constance Easterling, Jennifer Fairbank, Revathi Iyengar, Mark Klafter, Justin Lindquist, Ahmed H Sadek, Elizabeth Carmona Toro, Navin Verma, Brigith Patino Castro, Nadia Sukhraj-Singh, Joseph Berger, Eric Williamson, Salim Chahin, Dina Jacobs, Clyde Markowitz, Jessica Dobbins, Lauren Mace, Maria Martin, Ashley Pinckney, Amber Roberts, Islam Zaydan, Galen W Mitchell, Rock A Heyman, Ryan L Orie, Valerie R Suski, Kerry Oddis, Darlene Punjack, Eoin Flanagan, Avi Gadoth, Andrew McKeon, W Oliver Tobin, Anastasia Zekeridou, Katie Dunlay, Jessica Sagen, Jonathan L Carter, Bachir Estephan, Brent P Goodman, Charlene R Hoffman Snyder, Andrea Francone, Irene Galasky, Martha Thomas, Pavle Repovic, James Bowen, Angeli Mayadev, Peiqing Qian, Yuriko Courtney, Lauren Lennox, Robert Thomas Naismith, Anne Haney Cross, Emily Evans, Erin E Longbrake, Megan E Orchard, Gregory F Wu, Linda Heinrich, Susan Sommers, Faria Amjad, Erika Mitchell, Carlos Mora, Bethany Schreiber, Carlo Tornatore, Alexis Carlson, Sacha McCarthy, and Alexandria Oliver

Subjects
Adult, medicine.medical_specialty, Population, Placebo, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Complement inhibitor, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, education, Aquaporin 4, education.field_of_study, Neuromyelitis optica, business.industry, Neuromyelitis Optica, General Medicine, Eculizumab, medicine.disease, Comorbidity, ddc, Neurology, Concomitant, Rituximab, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT. Methods In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity. Results The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder. Conclusion Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate. Trial registration NCT01892345 (ClinicalTrials.gov).

Published
2020

9. Factors associated with poor anticoagulation control with vitamin K antagonists among outpatients attended in Internal Medicine and Neurology. The ALADIN study

Author

Cristina Barbagelata, Francisco Cabrera, María Herrera, Pedro Cardona, Radka Ivanova Georgieva, José Miguel Pons, Maite Martínez, Jesús Saiz, Tomás Pérez, José Ángel Satué, Cristina Tejera Pérez, Joan Rosal, Javier Fernández, M. José Gómez, Jordi Sanahuja, Patricia Ibáñez, Ana Rodríguez, José M. Errea, Alejandro Martínez-Domeño, Antonio Manquillo, Ana Latorre, Luis Beltrán, Juli Font, Cecile van Eedenburg, Xavier Ustrell, Elena Bello, Raquel González, M. Carmen Gil, José Antonio Díaz, Francisco Purroy, Elena Calzado, José Carlos Gómez, Susana Arias, Clara Sainz, Óscar Fabre, Francisco Javier Barrero, José Ferreiro, José M. Ramírez-Moreno, Mariano Aguayo, Lamberto Landete, Manuel Rodríguez, Ramón Villaverde, Eduardo Agüera-Morales, C. Suárez Fernández, José Ramírez, Gemma Reig, Covadonga Fernández, Carmen Jiménez, Ana M Roa, Alejandro Ponz, Joaquín Carnedo, Rafael Fernández de la Puerta, Jerzy Kuprinski, Raquel Chamarro, Enrique Cabrerizo, Rafael López, M. Ángeles Revilla, Xavier Nogués, Marta Serrano, Roberto Muñoz, José M. Trejo, Jaume Roquer, Beatriz Zandio, María Pérez de la Blanca, Santiago Montull, Helena Quesada, Juan Carlos Anglada, Ana de Arce, Ana Pampliega, Juan Carlos Belinchón, Jaime Gállego, Francisco Moniche, Inmaculada Villegas, Nuria Aymerich, Juan José Mengual, Ana Calleja, Antonio Gil-Núñez, Antonio Medina, Fernando Salgado, Antonio Pose, Blanca Batalla, Sandra Boned-Riera, Juan José Cara, José M. Terrero, Juan Luengo, Román Cerro, José Tembl, Laia Seró, Christian Homedes, Manuel Payan, Imma Cañas, Blanca Fuentes, Fernando Díaz, Laura Ballester, Francisco Lozano, Ignacio Casado, M. Pilar Moreno, Luis López, Antonio Arjona, Miguel Yebra, Jorge Romero, Marco Antonio Budiño, Francesc Puchades, Jacinto Hernández, Javier García, María Concepción Prados Sánchez, Joan Martí-Fàbregas, José Castro, M. Ángeles Fidalgo, Javier Marta, Alicia de Felipe, David Esteva, María Bestué, Vicente Oliver, Marta Guillan, David Vinuesa García, Esther Aragón, Natividad Raña, José Maciñeiras, José Luis Vázquez, Juan Carlos Martínez-Acitores, Dolores Fernández, Félix González, Demetrio Sánchez, Rafael Bustamante, María Ángeles Ortega, Nuria Navarrete, Jesús M. Juega, Emilio Barroso, Pedro Luis Muñoz, Leticia Álvarez, Mónica Arias, Carlos Sánchez, Juan Antonio Arroyo, Juan José Timiraos, Ana Jurado, José Carlos Pontes, Sonia M. García, Iluminada García Polo, Daniel Irigoyen, Arturo Artero, Maria Àngels Font, Miguel Ángel Rico, Laura Imaz, Salvadora Martínez, José Carlos Fernández, Ikram Benabdelhak, Ana María González, Patricia Martínez, Sonia Huertas, Francisco Javier Martínez, Yolanda Bravo, Alfonso Aguirre, Luis Mérida, Carlos Tejero, Jordi Espinosa, Montserrat González, Consuelo Matute, José M. de Lis, Marian Muchada, José Bernardo Escribano, M. Dolores Moragues, Miguel Ángel Corrales, Mar Freijo, Juan F. Arenillas, J. Manuel Cerqueiro, Aida Lago, Manuel Montero, Enrique Mostacero, Javier de la Torre, Jesús Foronda, David Gorriz, Óscar Fernández, Elisa Rodríguez, Alex Culla, José M. Rivera, Juan Carlos Portilla, Roberto Pérez, Marta Pena, Bárbara Vives, Julián Fernández, Jose Antonio Egido, Ana Castellano, Mónica Zamora, Agustín Pijierro, Eva Calvo, Elisa Cortijo, Fernando Aguilar, David Cánovas, José Vivancos, Pablo Irimia, Enrique Calderón, Carlos Molina, Pedro Jesús Serrano, Esther Fernández, J. Tejada, Carmen Morata, María Paz Martínez, Gerardo Ruiz, César Lucas, Purificación Durán, Ángel Ois, Noemí Díez, José Antonio Tamayo, Jordi Casanova, Igor Molina, Jaime Díaz, Carmen Caro, Susana Mederer, Fernando Jaén, Jordi Estela, Dionisio Carrillo, Irene Navalpotro, José Luis Beato Pérez, Alain Luna, Jorge Artal, Jesús Cantero, Enrique Palacio, Elisa Cuadrado, Javier Reyes, Pilar Meler, Miguel Alberto de Zarraga, Gema Sanz, M. Ángeles López, Ricardo Gómez, Joaquín Sánchez, Miguel Ángel García, Raúl Quirós, Rosario Gil, Héctor Guerrero, Jorge Marrero, Eduardo Carmona, José Carlos Morán, José Antonio Trujillo, Alan Flores, Juan Manuel García, Manuel Gómez-Choco, Amparo Romero, Carlos Vilar, Santiago Freire, M. del Mar Castellanos, Silvia Tur, Cristina Borrachero, Jesús Vega, Sonia Gonzalo, Alberto Morán, Laura Ramos, Antonio Cayon, Manuel Seijo, Raquel Delgado-Mederos, M. José Fonseca, Juan Girón, Aida Rodríguez, Yesica Miranda, Jaime Masjuan, Álvaro González, Iván Moreno, Fernando Sierra, Jordi Jiménez, M. del Carmen Riveira, Davinia Larrosa, Rosa Díaz, Daniel Peña, M.M. Contreras Muruaga, Joaquín Antón, Irene Escudero, Borja Enrique Sanz, and Antoni German

Subjects
medicine.medical_specialty, Acenocoumarol, Neurology, business.industry, Warfarin, Atrial fibrillation, General Medicine, 030204 cardiovascular system & hematology, Vitamin k, medicine.disease, Thromboembolic risk, 03 medical and health sciences, 0302 clinical medicine, Multicenter study, Diabetes mellitus, Internal medicine, medicine, 030212 general & internal medicine, business, medicine.drug
Abstract

Objective To identify factors associated with poor anticoagulation control with vitamin K antagonists (VKA) among outpatients with nonvalvular atrial fibrillation (NVAF) attended in Neurology and Internal Medicine in Spain. Methods Cross-sectional and multicenter study, from the ALADIN database, of outpatients with NVAF treated with VKA and attended in Internal Medicine and Neurology in Spain. Rates of anticoagulation control were determined with the direct and Rosendaal methods, considering data from the 6 months before the inclusion. Results Out of 1337 patients included in the ALADIN study, 750 were taking VKA, and complete information about INR values in the last 6 months was available in 383 patients. Mean scores of Charlson Index, CHADS2, CHA2DS2-VASc and HAS-BLED were 1.94 ± 1.54; 3.10 ± 1.26; 4.63 ± 1.54, and 2.20 ± 0.90, respectively. 46.2% and 47.0% of patients had an adequate anticoagulation control according to the direct and Rosendaal methods, respectively. Inadequate anticoagulation control according to the direct method was associated with diabetes (OR: 2.511; 95% CI: 1.144–5.659), prior labile INR (OR: 35.371; 95% CI: 15.058–83.083) and the determination of >6 INR controls in the last 6 months (OR: 4.747; 95% CI: 2.094–10.759), and according to the Rosendaal method, with prior labile INR (p Conclusions Despite the high thromboembolic risk, only a little more than a half of patients were well controlled. Factors associated with poor anticoagulation control were diabetes, labile INR, >6 INR controls and HAS-BLED.

Published
2018
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10. Factores asociados al mal control de la anticoagulación con antivitamina K en pacientes con fibrilación auricular no valvular atendidos en consultas de Medicina Interna y Neurología. Estudio ALADIN

Author

M.M. Contreras Muruaga, G. Reig, J. Vivancos, A. González, P. Cardona, J.M. Ramírez-Moreno, J. Martí-Fábregas, C. Suárez Fernández, Antonio Pose, José Antonio Díaz, Manuel Rodríguez, Marta Pena, Susana Arias, Davinia Larrosa, Álvaro González, Elisa Rodríguez, Montserrat González, Dolores Fernández, Cristina Barbagelata, Natividad Raña, Santiago Freire, J. Manuel Cerqueiro, Héctor Guerrero, Laura Ramos, Leticia Álvarez, José M. de Lis, Carmen Caro, Manuel Seijo, Susana Mederer, Miguel Alberto de Zarraga, José Ferreiro, José M. Terrero, Mónica Arias, Roberto Pérez, Joaquín Sánchez, José Maciñeiras, Julián Fernández, Fernando Jaén, David Esteva, Mónica Zamora, Nuria Navarrete, Javier García, Luis Mérida, Miguel Ángel Corrales, Raúl Quirós, Jesús Cantero, Francisco Javier Barrero, Inmaculada Villegas, José Castro, Jesús Foronda, Dionisio Carrillo, Jesús Vega, José Antonio Trujillo, Manuel Montero, Ana Jurado, Carlos Sánchez, Eduardo Agüera-Morales, María Sánchez, Purificación Durán, Rafael Fernández de la Puerta, María Pérez de la Blanca, María Paz Martínez, Óscar Fernández, José Antonio Tamayo, Rafael Bustamante, Pedro Jesús Serrano, Antonio Arjona, Javier Fernández, Manuel Payan, Ricardo Gómez, Daniel Peña, Enrique Cabrerizo, Fernando Salgado, Radka Ivanova Georgieva, Antonio Gil-Núñez, Elena Bello, Fernando Díaz, Antonio Medina, Ana Castellano, Yesica Miranda, Óscar Fabre, Iluminada García Polo, Patricia Ibáñez, Clara Sainz, Fernando Sierra, Esther Aragón, Jaime Díaz, Fernando Aguilar, María Ángeles Ortega, José Antonio Egido, José Carlos Pontes, Miguel Ángel García, Francisco Cabrera, Blanca Batalla, Alex Culla, Carlos Molina, Alan Flores, Laia Seró, Marian Muchada, Pilar Meler, Sandra Boned-Riera, David Cánovas, Jordi Estela, Juli Font, Francisco Purroy, Ikram Benabdelhak, Jordi Sanahuja, Jaume Roquer, Ana Rodríguez, Ángel Ois, Elisa Cuadrado, Jordi Jiménez, Xavier Nogués, Jerzy Kuprinski, Antoni German, Daniel Irigoyen, Juan José Cara, Maria Àngels Font, Sonia Huertas, Alejandro Martínez-Domeño, Juan Antonio Arroyo, Raquel Delgado-Mederos, Manuel Jesús Gómez-Choco, Juan José Mengual, Sonia M. García, M. del Mar Castellanos, Cecile van Eedenburg, Imma Cañas, Jordi Espinosa, Santiago Montull, Helena Quesada, Xavier Ustrell, Christian Homedes, Irene Navalpotro, Jordi Casanova, Aida Pilar Lago, Carmen Morata, David Gorriz, Iván Moreno, José Tembl, Alejandro Ponz, M. José Fonseca, Raquel Chamarro, Rosario Gil, Vicente Oliver, Ana Pampliega, Arturo Artero, Francesc Puchades, Lamberto Landete, Carlos Vilar, Carmen Jiménez, Bárbara Vives, M. Dolores Moragues, Rosa Díaz, Silvia Tur, José Bernardo Escribano, César Lucas, Francisco Martínez, José Miguel Pons, Amparo Romero, David García, José Pérez, Ramón Villaverde, Salvadora Martínez, Aida Rodríguez, Carlos Tejero, Cristina Pérez, Enrique Mostacero, Covadonga Fernández, Alain Luna, Tomás Pérez, Félix González, Ana de Arce, Maite Martínez, Noemí Díez, Jaime Gállego, Beatriz Zandio, María Herrera, Nuria Aymerich, Roberto Muñoz, Javier Marta, Jorge Artal, José M. Errea, Juan José Timiraos, M. Pilar Moreno, Mar Freijo, Juan Manuel García, M. Carmen Gil, M. Ángeles Revilla, Enrique Palacio, José Luis Vázquez, María Bestué, Ana Latorre, Eva Calvo, Laura Ballester, Marta Serrano, Jesús M. Juega, M. Ángeles López, Pablo Irimia, Laura Imaz, Blanca Fuentes, Borja Enrique Sanz, Luis Beltrán, Gerardo Ruiz, Patricia Martínez, Demetrio Sánchez, Emilio Barroso, Igor Molina, Marco Antonio Budiño, Jaime Masjuan, Alicia de Felipe, Consuelo Matute, Javier Tejada, Alberto Morán, Esther Fernández, M. del Carmen Riveira, Joaquín Carnedo, Antonio Manquillo, Raquel González, José Carlos Fernández, Marta Guillan, Miguel Yebra, José M. Trejo, Jesús Saiz, Juan Carlos Martínez-Acitores, Yolanda Bravo, Juan Francisco Arenillas, Ana Calleja, Elisa Cortijo, Javier Reyes, Luis López, Pedro Luis Muñoz, M. Ángeles Fidalgo, Jacinto Hernández, José Carlos Gómez, José Carlos Morán, Sonia Gonzalo, Jorge Marrero, José Ángel Satué, Juan Carlos Belinchón, Francisco Moniche, Enrique Calderón, Irene Escudero, Javier de la Torre, Ignacio Casado, Joaquín Antón, Juan Carlos Portilla, Juan Luengo, Joan Rosal, Elena Calzado, Juan Carlos Anglada, Juan Girón, José M. Ramírez, Agustín Pijierro, Ana Roa, Jorge Romero, Mariano Aguayo, Cristina Borrachero, Gema Sanz, M. José Gómez, Miguel Ángel Rico, Antonio Cayon, Eduardo Carmona, Román Cerro, Rafael López, Alfonso Aguirre, Francisco Lozano, and José M. Rivera.

Subjects
03 medical and health sciences, 0302 clinical medicine, business.industry, Medicine, 030212 general & internal medicine, General Medicine, 030204 cardiovascular system & hematology, business, Humanities
Abstract

Resumen Objetivo Identificar los factores asociados con el mal control de la anticoagulacion con antagonistas de la vitamina K (AVK) en pacientes con fibrilacion auricular no valvular (FANV) atendidos en consultas de Neurologia y Medicina Interna de Espana. Metodos Estudio transversal, multicentrico, anidado en el estudio ALADIN, de sujetos con FANV, tratados con AVK, atendidos en consultas de Medicina Interna o Neurologia de Espana. El grado de control de la anticoagulacion se estudio mediante el metodo directo y el de Rosendaal, considerando los 6 meses previos a la inclusion. Resultados De los 1.337 pacientes incluidos en ALADIN, 750 estaban tratados con AVK, con informacion completa sobre el INR de los ultimos 6 meses en 383 pacientes. Las puntuaciones medias del indice de Charlson, CHADS2, CHA2DS2-VASc y HAS-BLED fueron 1,94 ± 1,54; 3,10 ± 1,26; 4,63 ± 1,54 y 2,20 ± 0,90, respectivamente. El 46,2% y el 47,0% de los pacientes presentaban un control adecuado de la anticoagulacion por los metodos directo y Rosendaal, respectivamente. El control inadecuado de la anticoagulacion se asocio por el metodo directo con diabetes (OR: 2,511; IC 95%: 1,144-5,659), antecedentes de INR inestable (OR: 35,371; IC 95%: 15,058-83,083) y la realizacion de > 6 controles en los ultimos 6 meses (OR: 4,747; IC 95%: 2,094-10,759), y por el metodo de Rosendaal, con los antecedentes de INR inestable (p Conclusiones Pese al alto riesgo tromboembolico, solo estaban bien controlados algo mas de la mitad. Los factores asociados al mal control de la anticoagulacion fueron la diabetes, INR inestable, > 6 controles de INR y el HAS-BLED.

Published
2018
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11. Machine-learning-based prediction of disability progression in multiple sclerosis: An observational, international, multi-center study.

Author

Edward De Brouwer, Thijs Becker, Lorin Werthen-Brabants, Pieter Dewulf, Dimitrios Iliadis, Cathérine Dekeyser, Guy Laureys, Bart Van Wijmeersch, Veronica Popescu, Tom Dhaene, Dirk Deschrijver, Willem Waegeman, Bernard De Baets, Michiel Stock, Dana Horakova, Francesco Patti, Guillermo Izquierdo, Sara Eichau, Marc Girard, Alexandre Prat, Alessandra Lugaresi, Pierre Grammond, Tomas Kalincik, Raed Alroughani, Francois Grand'Maison, Olga Skibina, Murat Terzi, Jeannette Lechner-Scott, Oliver Gerlach, Samia J Khoury, Elisabetta Cartechini, Vincent Van Pesch, Maria José Sà, Bianca Weinstock-Guttman, Yolanda Blanco, Radek Ampapa, Daniele Spitaleri, Claudio Solaro, Davide Maimone, Aysun Soysal, Gerardo Iuliano, Riadh Gouider, Tamara Castillo-Triviño, José Luis Sánchez-Menoyo, Anneke van der Walt, Jiwon Oh, Eduardo Aguera-Morales, Ayse Altintas, Abdullah Al-Asmi, Koen de Gans, Yara Fragoso, Tunde Csepany, Suzanne Hodgkinson, Norma Deri, Talal Al-Harbi, Bruce Taylor, Orla Gray, Patrice Lalive, Csilla Rozsa, Chris McGuigan, Allan Kermode, Angel Pérez Sempere, Simu Mihaela, Magdolna Simo, Todd Hardy, Danny Decoo, Stella Hughes, Nikolaos Grigoriadis, Attila Sas, Norbert Vella, Yves Moreau, and Liesbet Peeters

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

BackgroundDisability progression is a key milestone in the disease evolution of people with multiple sclerosis (PwMS). Prediction models of the probability of disability progression have not yet reached the level of trust needed to be adopted in the clinic. A common benchmark to assess model development in multiple sclerosis is also currently lacking.MethodsData of adult PwMS with a follow-up of at least three years from 146 MS centers, spread over 40 countries and collected by the MSBase consortium was used. With basic inclusion criteria for quality requirements, it represents a total of 15, 240 PwMS. External validation was performed and repeated five times to assess the significance of the results. Transparent Reporting for Individual Prognosis Or Diagnosis (TRIPOD) guidelines were followed. Confirmed disability progression after two years was predicted, with a confirmation window of six months. Only routinely collected variables were used such as the expanded disability status scale, treatment, relapse information, and MS course. To learn the probability of disability progression, state-of-the-art machine learning models were investigated. The discrimination performance of the models is evaluated with the area under the receiver operator curve (ROC-AUC) and under the precision recall curve (AUC-PR), and their calibration via the Brier score and the expected calibration error. All our preprocessing and model code are available at https://gitlab.com/edebrouwer/ms_benchmark, making this task an ideal benchmark for predicting disability progression in MS.FindingsMachine learning models achieved a ROC-AUC of 0⋅71 ± 0⋅01, an AUC-PR of 0⋅26 ± 0⋅02, a Brier score of 0⋅1 ± 0⋅01 and an expected calibration error of 0⋅07 ± 0⋅04. The history of disability progression was identified as being more predictive for future disability progression than the treatment or relapses history.ConclusionsGood discrimination and calibration performance on an external validation set is achieved, using only routinely collected variables. This suggests machine-learning models can reliably inform clinicians about the future occurrence of progression and are mature for a clinical impact study.

Published
2024
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12. HIV infection and multiple sclerosis: a case with unexpected 'no evidence of disease activity' status

Author

Ángela Monterde Ortega, Eduardo Agüera Morales, María Del Carmen Blanco-Valero, Alba Rodrígez-Martín, Fernando Acebrón, Fernando Labella, [Labella,F, Acebrón,F, Blanco-Valero,MDC, Rodrígez-Martín,A, Monterde Ortega,A, Agüera Morales,E] Unidad de Gestión Clínica de Neurologia, Hospital Universitario Reina Sofía, Córdoba. [Agüera Morales,E] Maimonides Biomedical Research Institute of Cordoba (IMIBIC)., and This study was funded by Instituto de Salud Carlos III through the project 'RD16/0015/0026' (co-funded by the European Regional Development Fund/European Social Fund, 'Investing in your future').

Subjects
0301 basic medicine, Medicine (General), medicine.medical_treatment, Human immunodeficiency virus (HIV), Case Report, HIV Infections, medicine.disease_cause, Biochemistry, Epstein–Barr virus, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, immunosuppression, human immunodeficiency virus, Human immunodeficiency virus, Incidence (epidemiology), Human endogenous retrovirus, Immunosuppression, General Medicine, highly active antiretroviral therapy, Organisms::Viruses [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunosuppression [Medical Subject Headings], medicine.anatomical_structure, Viruses, No evidence of disease activity, Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [Medical Subject Headings], Diseases::Immune System Diseases::Autoimmune Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [Medical Subject Headings], Central nervous system, Retrovirus endógenos, Multiple sclerosis, Disease activity, 03 medical and health sciences, Highly active antiretroviral therapy, Multiple Sclerosis, Relapsing-Remitting, R5-920, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], medicine, Humans, no evidence of disease activity, Anatomy::Nervous System::Central Nervous System [Medical Subject Headings], business.industry, Biochemistry (medical), VIH, Herpesvirus humano 4, Cell Biology, Terapia antirretroviral altamente activa, medicine.disease, Terapia de inmunosupresión, human endogenous retrovirus, 030104 developmental biology, Esclerosis múltiple, Immunology, Etiology, business, 030217 neurology & neurosurgery
Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system whose etiology remains unclear. It has been suggested that MS can be triggered by certain viruses; however, human immunodeficiency virus (HIV) infection is associated with reduced incidence of MS. We present the case of a young patient diagnosed with active relapsing-remitting MS whose clinical course substantially improved following HIV infection and treatment. The patient achieved no evidence of disease activity status without any disease-modifying drugs. Both HIV-induced immunosuppression and antiretroviral therapy may have attenuated the clinical course in this patient.

Published
2021
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13. Decompressive Hemicraniectomy without Evacuation of Acute Intraparenchymal Hemorrhage

Author

Cristóbal Blanco-Acevedo, Eduardo Aguera-Morales, Antonio C. Fuentes-Fayos, Nazareth Pelaez-Viña, Rosa Diaz-Pernalete, Nazaret Infante-Santos, Ana Muñoz-Jurado, Manuel F. Porras-Pantojo, Alejandro Ibáñez-Costa, Raúl M. Luque, and Juan Solivera-Vela

Subjects
intracerebral hemorrhage, intraparenchymal hematoma, decompressive craniectomy, clot evacuation, Biology (General), QH301-705.5
Abstract

Background: Intracerebral hemorrhages (ICHs) are prevalent, with high morbidity and mortality. We analyzed whether decompressive craniectomy (DC) without evacuation of the acute intraparenchymal hematoma could produce better functional outcomes than treatment with evacuation. Methods: Patients with acute ICH treated with DC without clot evacuation, or evacuation with or without associated craniectomy were included. Matched univariate analyses were performed, and a binary logistic regression model was constructed using the Glasgow Outcome Scale (GOS) and modified Rankin scale (mRS) as dependent variables. Results: 27 patients treated with DC without clot evacuation were compared to 36 patients with clot evacuation; eleven of the first group were matched with 18 patients with evacuation. A significantly better functional prognosis in the group treated with DC without clot evacuation was found. Patients aged < 55 years and treated with DC without clot evacuation had a significantly better functional prognosis (p = 0.008 and p = 0.039, respectively). In multivariate analysis, the intervention performed was the greatest predictor of functional status at the end of follow-up. Conclusions: DC without clot evacuation improves the functional prognosis of patients with acute intraparenchymal hematomas. Larger multicenter studies are warranted to determine whether a change in the management of acute ICH should be recommended.

Published
2024
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14. Autores

Author

Eduardo Agüera Morales, Miguel Alonso Alonso, Pablo Arias Rodríguez, David Bartrés-Faz, Michela Campolo, Joan A. Camprodon Giménez, M.ª del Carmen Carrasco López, F. Javier Cudeiro Mazaira, René Drucker-Colin, Nelson Espinosa Vergara, Mauro García-Toro, Margalida Gili Planas, Ignacio Jimena Medina, Ricardo López-Martos, Evelio Luque Carabot, Francisco J. Medina Fernández, Helena Mondragón Llorca, Laura Mordillo Mateos, Antonio Oliviero, Álvaro Pascual Leone, José Peña Amaro, Cleofé Peña-Gómez, Miguel Roca Bennasar, Belén Rubio Morell, Fernando Sánchez López, Vanesa Soto León, Inmaculada Tasset Cuevas, Isaac Túnez Fiñana, Josep Valls-Solé, and Leticia Verdugo-Díaz

Published
2014
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15. Effect of the Mediterranean diet and probiotic supplementation in the management of mild cognitive impairment: Rationale, methods, and baseline characteristics

Author

Magdalena P. Cardelo, Andreea Corina, Ana Leon-Acuña, Gracia M. Quintana-Navarro, Juan F. Alcala-Diaz, Oriol Alberto Rangel-Zuñiga, Antonio Camargo, Cristina Conde-Gavilan, Claudia Carmona-Medialdea, Juan A. Vallejo-Casas, Elvira Carmona-Asenjo, Juan J. Ochoa-Sepulveda, Eduardo Aguera-Morales, Javier Delgado-Lista, Niki Katsiki, José Lopez-Miranda, Francisco Perez-Jimenez, Elena M. Yubero-Serrano, and Pablo Perez-Martínez

Subjects
mild cognitive impairment, Mediterranean diet, dietary strategies, probiotics, gut-brain axis, Nutrition. Foods and food supply, TX341-641
Abstract

IntroductionMild cognitive impairment (MCI) can progress to Alzheimer’s disease (AD). When MCI is not properly controlled, the speed of deterioration can dramatically increase. Reduction of oxidative stress/inflammation and the modulation of the gut-brain axis could be new potential therapeutic targets for the prevention and treatment of AD. Consumption of specific nutrients, diets and probiotic supplementation have been evaluated for neurodegenerative disorders. We focus on a detailed description of the study methods and baseline characteristics of a clinical trial aiming to evaluate the efficacy of a combined nutritional intervention, i.e., a Mediterranean diet with probiotics, on cognitive capacity in a population with MCI.MethodsIn this randomized, latin-square crossover, double-blind, and controlled dietary intervention trial (clinicaltrials.gov NCT05029765), 47 MCI patients were randomized to consume three dietary interventions for 24-weeks each: (1) A Mediterranean diet supplemented with probiotics (109 colony-forming units of Lactobacillus rhamnosus and Bifidobacterium longum); (2) A Mediterranean diet + placebo; and (3) A Healthy diet according to the World Health Organization (WHO) recommendations. Participants will be evaluated before and after each of the three intervention periods (each 24-weeks, with a total of 72-weeks) for adherence to the assigned diet, blood tests, cognitive performance, gut microbiota analysis and functional neuroimaging studies.ResultsFifty patients, ≥60 years-old and diagnosed with MCI, underwent randomization. A total of 47 patients completed follow-up dietary interventions (57.4% males), with a good glycemic control (HbA1c 5.8 ± 0.1%, fasting glucose and insulin 99.7 ± 3.3 mg/dL and 10.4 ± 0.9 mU/L, respectively), elevated systolic blood pressure (136.9 ± 2.1 mmHg) and increased degree of inflammation (high-sensitivity C-reactive protein, 8.8 ± 0.9 mg/dL). Baseline adherence to the Mediterranean diet was medium (7.5 ± 0.3 points on the score that ranged from 0 to 14 points).ConclusionThe results of this clinical study would provide more evidence on the need for dietary therapeutic strategies, for clinical and individual practice, in the management of MCI patients to reduce the risk of AD development. Targeting lifestyle modifications in high-risk populations could prevent substantial cases of cognitive decline.Clinical trial registration[ClinicalTrials.gov], identifier [NCT05029765].

Published
2022
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16. Effectiveness and safety of PCSK9 inhibitors in real-world clinical practice. An observational multicentre study. The IRIS-PCSK9I study

Author

Marina Blanco-Ruiz, Laura Amaya-Pascasio, Reyes de Torres Chacón, María Josefa Álvarez Soria, Antonio Arjona-Padillo, María Magdalena Carrillo Bailén, Rodrigo Milán Pinilla, Irene Pérez Ortega, Belén Sánchez Rodríguez, Luis Andrade Zumárraga, Roberto Valverde Moyano, Manuel Payán Ortiz, Alba María Castillo Fernández, Cristina Del Toro Pérez, Pablo González Bustos, Eduardo Agüera Morales, Purificación Sánchez López, Beatriz Hidalgo Martín, Ricardo Roa Chamorro, Javier Fernández Pérez, María Victoria Mejías Olmedo, and Patricia Martínez-Sánchez

Subjects
Evolocumab, Alirocumab, PCSK9i, Hypercholesterolemia familiar, Cardiovascular disease, Statins intolerance, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background and aims: The benefits of the PCSK9 inhibitors, alirocumab and evolocumab, in lowering LDL-cholesterol and preventing major adverse cardiac events (MACE) have been demonstrated in pivotal clinical trials. However, few studies of routine clinical practice have been conducted to analyse and compare the efficacy and safety of the two drugs. Methods: Retrospective observational study of patients treated with a PCSK9 inhibitor in five hospitals in Andalusia (southern Spain). Baseline demographic and clinical data, LDL-cholesterol levels and the occurrence of MACEs during the follow-up period were recorded. Results: A total of 141 patients were included in the study: 90 were treated with alirocumab and 51 with evolocumab. The patients’ mean age (IQR) was 58 (11) years and 58 (41%) were women. The most frequent concomitant medications were statins, 94 (66.7%), followed by antiplatelet therapy (66%) and ezetimibe (65.2%). The median (IQR) follow-up period was 18 (18) months, with 18 (24) for alirocumab and 11 (18) for evolocumab. At the six-month follow-up visit, LDL-cholesterol values had decreased to pre-treatment levels and remained significantly decreased (p

Published
2021
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