Search

Your search keyword '"Fiedler, J."' showing total 12 results
Start Over Author "Fiedler, J." Topic humans
12 results on '"Fiedler, J."'

1. Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics

Author

Stojanovic, S.D., Fuchs, M., Liang, C., Schmidt, K., Xiao, K., Just, A., Pfanne, A., Pich, A., Warnecke, G., Braubach, P., Petzold, C., Jonigk, D., Distler, J.H.W., Fiedler, J., Thum, T., Kunz, M., and Publica

Subjects
Science, Primary Cell Culture, Datasets as Topic, Diseases, Pathogenesis, Article, Protein Interaction Mapping, Humans, Gene Regulatory Networks, ddc:610, Protein Interaction Maps, Lung, Cells, Cultured, Gene Expression Profiling, Computational Biology, RNA-Binding Proteins, Fibroblasts, respiratory system, Idiopathic Pulmonary Fibrosis, Computational biology and bioinformatics, respiratory tract diseases, MicroRNAs, Gene Expression Regulation, Case-Control Studies, Medicine, Single-Cell Analysis
Abstract

The family of RNA-binding proteins (RBP) functions as a crucial regulator of multiple biological processes and diseases. However, RBP function in the clinical setting of idiopathic pulmonary fibrosis (IPF) is still unknown. We developed a practical in silico screening approach for the characterization of RBPs using multi-sources data information and comparative molecular network bioinformatics followed by wet-lab validation studies. Data mining of bulk RNA-Sequencing data of tissues of patients with IPF identified Quaking (QKI) as a significant downregulated RBP. Cell-type specific expression was confirmed by single-cell RNA-Sequencing analysis of IPF patient data. We systematically analyzed the molecular interaction network around QKI and its functional interplay with microRNAs (miRs) in human lung fibroblasts and discovered a novel regulatory miR-506-QKI axis contributing to the pathogenesis of IPF. The in silico results were validated by in-house experiments applying model systems of miR and lung biology. This study supports an understanding of the intrinsic molecular mechanisms of IPF regulated by the miR-506-QKI axis. Initially applied to human lung disease, the herein presented integrative in silico data mining approach can be adapted to other disease entities, underlining its practical relevance in RBP research.

Published
2021

2. Giant intracranial aneurysms: Natural history and 1-year case fatality after endovascular or surgical treatment

Author

Dengler, Julius, Rüfenacht, Daniel, Meyer, Bernhard, Rohde, Veit, Endres, Matthias, Lenga, Pavlina, Uttinger, Konstantin, Rücker, Viktoria, Kursumovic, Adisa, Hong, Bujung, Mielke, Dorothee, Schmidt, Nils Ole, Burkhardt, Jan-Karl, Bijlenga, Philippe, Boccardi, Edoardo, Cognard, Christophe, Heuschmann, Peter U., Vajkoczy, Peter, Bauknecht, H.C., Bohner, G., Liebig, T., Wiener, E., Gläsker, S., Klingler, J.-H., Scheiwe, C., van Velthoven, V., Zentner, J., Durner, G., König, R., Pedro, M.T., Wirtz, R., Fiss, I., Kombos, T., Guhl, S., Schroeder, H.W.S., Strowitzki, M., Eicker, S., Steiger, H., Turowski, B., Abdulazim, A., Etminan, N., Haenggi, D., Kalff, R., Walter, J., Brawanski, A., Schebesch, K.M., Ardeshiri, A., Sure, Ulrich, Wrede, Karsten, Schmidt, N.O., Regelsberger, J., Westphal, M., Hosch, H., Moskopp, D., Hohaus, C., Meisel, H.J., Lehmberg, J., Wostrack, M., Ganslandt, O., Hopf, N., Musahl, C., Graewe, A., Meier, U., Krauss, J., Nakamura, M., Grote, A., Güresir, E., Schramm, J., Simon, M., Vatter, H., Rath, S.A., Boxhammer, E., Hoffmann, K.T., Diepers, M., Fandino, J., Marbacher, S., Familiari, P., Raco, A., Schaller, K., Gruber, A., Knosp, E., Wang, W.T., Rüfenacht, D.A., Wanke, I., Piano, M., Hernesniemi, J., Lehecka, M., Niemelä, M., Nurminen, V., Burkhardt, J.K., Bozinov, O., Maldaner, N., Regli, L., Eliava, S.S., Shekhtman, O.D., Helthuis, J., van Doormaal, T., van der Zwan, A., Dammers, R., Dirven, C.M.F., Gawlitza, M., Guenego, A., Fiedler, J., Kato, N., Murayama, Y., Dabus, G., Linfante, I., Starosciak, A.K., Miran, M.S., Suri, M.F.K., and Neurosurgery

Subjects
Male, Risk, medicine.medical_specialty, Subarachnoid hemorrhage, Medizin, Aneurysm, Ruptured, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, medicine.artery, Case fatality rate, medicine, Aphasia, Humans, Giant intracranial aneurysm, cardiovascular diseases, Aneurysm rupture, Prospective Studies, Registries, Surgical treatment, Prospective cohort study, Aged, Retrospective Studies, Movement Disorders, business.industry, Endovascular Procedures, Angiography, Digital Subtraction, Vascular disorders, Retrospective cohort study, Intracranial Aneurysm, General Medicine, Middle Aged, medicine.disease, ddc:616.8, 3. Good health, Surgery, Natural history, Europe, Hospitalization, Treatment Outcome, 030220 oncology & carcinogenesis, Relative risk, cardiovascular system, Female, Internal carotid artery, business, Vascular Surgical Procedures, 030217 neurology & neurosurgery
Abstract

OBJECTIVEClinical evidence on giant intracranial aneurysms (GIAs), intracranial aneurysms with a diameter of at least 25 mm, is limited. The authors aimed to investigate the natural history, case fatality, and treatment outcomes of ruptured and unruptured GIAs.METHODSIn this international observational registry study, patients with a ruptured or unruptured GIA received conservative management (CM), surgical management (SM), or endovascular management (EM). The authors investigated rupture rates and case fatality.RESULTSThe retrospective cohort comprised 219 patients with GIAs (21.9% ruptured GIAs and 78.1% unruptured GIAs) whose index hospitalization occurred between January 2006 and November 2016. The index hospitalization in the prospective cohort (362 patients with GIAs [17.1% ruptured and 82.9% unruptured]) occurred between December 2008 and February 2017. In the retrospective cohort, the risk ratio for death at a mean follow-up of 4.8 years (SD 2.2 years) after CM, compared with EM and SM, was 1.63 (95% CI 1.23–2.16) in ruptured GIAs and 3.96 (95% CI 2.57–6.11) in unruptured GIAs. In the prospective cohort, the 1-year case fatality in ruptured GIAs/unruptured GIAs was 100%/22.0% during CM, 36.0%/3.0% after SM, and 39.0%/12.0% after EM. Corresponding 1-year rupture rates in unruptured GIAs were 25.0% during CM, 1.2% after SM, and 2.5% after EM. In unruptured GIAs, the HR for death within the 1st year in patients with posterior circulation GIAs was 6.7 (95% CI 1.5–30.4, p < 0.01), with patients with a GIA at the supraclinoid internal carotid artery as reference. Different sizes of unruptured GIAs were not associated with 1-year case fatality.CONCLUSIONSRupture rates for unruptured GIAs were high, and the natural history and treatment outcomes for ruptured GIAs were poor. Patients undergoing SM or EM showed lower case fatality and rupture rates than those undergoing CM. This difference in outcome may in part be influenced by patients in the CM group having been found poor candidates for SM or EM.Clinical trial registration no.: NCT02066493 (clinicaltrials.gov)

Published
2021

3. Sodium intake and multiple sclerosis activity and progression in BENEFIT

Author

Fitzgerald, Kathryn C., Munger, Kassandra L., Hartung, H. -P., Freedman, M., Montalbán, Xavier, Edan, G., Wicklein, Eva-Maria, Radue, Ernst-Wilhelm, Kappos, L., Pohl, Christoph, Ascherio, Alberto, Strasser-Fuchs, S., Berger, T., Vass, K., Sindic, C., Dubois, B., Dive, D., Debruyne, J., Metz, L., Rice, G., Duquette, P., Lapierre, Y., Traboulsee, A., O'Connor, P., Štourač, P., Talab, R., Zapletalova, O., Kovařova, I., Medova, E., Fiedler, J., Frederiksen, J., Brochet, B., Moreau, T., Vermersch, P., Pelletier, J., Clanet, M., Clavelou, P., Lebrun-Frenay, C., Gout, O., Kallela, M., Pirttila, T., Ruutiainen, J., Koivisto, K., Reunanen, M., Elovaara, I., Villringer, A., Altenkirch, H., Wessel, K., Steinke, W., Kölmel, H., Oschmann, P., Diem, R., Dressel, A., Hoffmann, F., Baum, K., Jung, S., Petereit, H., Reske, D., Sailer, M., Kohler, J., Sommer, N., Hohlfeld, R., Henn, K. -H., Tumani, H., Gold, R., Rieckmann, P., Komoly, R., Gacs, G., Jakab, G., Csiba, L., Vecsei, L., Miller, A., Karussis, D., Chapman, J., Ghezzi, A., Comi, G., Gallo, P., Cosi, V., Durelli, L., Anten, B., Visser, L., Myhr, K. -M., Szczudlik, A., Selmaj, K., Stelmasiak, Z., Podemski, R., Maciejek, Z., Cunha, L., Sega-Jazbec, S., Montalban, X., Arbizu, T., Saiz, A., Barcena, J., Arroyo, R., Fernandez, O., Izquierdo, G., Casanova, B., Lycke, J., Mattle, H., Beer, K., Coleman, R., Chataway, J., Riordan, J. O., Howell, S., Johns Hopkins University (JHU), Harvard T.H. Chan School of Public Health, Department of neurology, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], The Ottawa Hospital, Medical Image Analysis Center (MIAC AG), Vall d'Hebron University Hospital [Barcelona], Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Bayer Pharma AG [Berlin], University Hospital Basel [Basel], Department of Neurology [Suisse], RG5146A1, National Multiple Sclerosis Society, NS071082, National Institute of Neurological Disorders and Stroke, Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), and Barillot, Christian

Subjects
Adult, Male, Multiple Sclerosis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Sodium, Dietary, Brain, Neuroimaging, Sodium, Dietary, Demyelinating Diseases, Disability Evaluation, Disease Progression, Female, Humans, Interferon beta-1b, Magnetic Resonance Imaging, Young Adult, Neurology, Neurology (clinical), Article, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Adult Brain/pathology Demyelinating Diseases/diagnosis* Demyelinating Diseases/drug therapy Demyelinating Diseases/pathology Demyelinating Diseases/urine Disability Evaluation Disease Progression Female Humans Interferon beta-1b/therapeutic use Magnetic Resonance Imaging Male Multiple Sclerosis/diagnosis* Neuroimaging Sodium, Dietary/adverse effects* Sodium, Dietary/urine Young Adult
Abstract

International audience; Objective - To assess whether a high-salt diet, as measured by urinary sodium concentration, is associated with faster conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and MS activity and disability. Methods - BENEFIT was a randomized clinical trial comparing early versus delayed interferon beta-1b treatment in 465 patients with a CIS. Each patient provided a median of 14 (interquartile range = 13-16) spot urine samples throughout the 5-year follow-up. We estimated 24-hour urine sodium excretion level at each time point using the Tanaka equations, and assessed whether sodium levels estimated from the cumulative average of the repeated measures were associated with clinical (conversion to MS, Expanded Disability Status Scale [EDSS]) and magnetic resonance imaging (MRI) outcomes. Results - Average 24-hour urine sodium levels were not associated with conversion to clinically definite MS over the 5-year follow-up (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.67-1.24 per 1g increase in estimated daily sodium intake), nor were they associated with clinical or MRI outcomes (new active lesions after 6 months: HR = 1.05, 95% CI = 0.97-1.13; relative change in T2 lesion volume: -0.11, 95% CI = -0.25 to 0.04; change in EDSS: -0.01, 95% CI = -0.09 to 0.08; relapse rate: HR = 0.78, 95% CI = 0.56-1.07). Results were similar in categorical analyses using quintiles. Interpretation - Our results, based on multiple assessments of urine sodium excretion over 5 years and standardized clinical and MRI follow-up, suggest that salt intake does not influence MS disease course or activity. Ann Neurol 2017;82:20-29.

Published
2017

4. Status update and interim results from the asymptomatic carotid surgery trial-2 (ACST-2)

Author

Bulbulia, R, Gray, W, Naughten, A, den Hartog, A, Delmestri, A, Wallis, C, le Conte, S, Macdonald, S, Radak, D, Nessi, F, Torsello, G, Hendriks, J, Bjorses, K, Davidovic, L, Tusini, N, Gillgren, P, Casana, R, Tolva, V, Bausback, Y, Mehrzad, A, Gottsäter, A, Esisi, B, Cras, P, Hendriks, Jm, Lauwers, P, Hertoghs, M, Van Schil, P, De Jaegher, L, Peeters, P, Verbist, J, Dendooven, D, De Letter, J, Vanhooren, G, Astarci, P, Capron, I, Choghari, C, Hammer, F, Lacroix, V, Peeters, A, Verhelst, R, Bosiers, M, De Meester, K, Deloose, K, Van Buggenhout, E, Vinck, E, Geenens, M, Hemelsoet, D, Van Herzeele, I, Vermassen, F, De Koster, G, Desiron, Q, Maertens de Noordhout, A, Malmendier, D, Massoz, M, Saad, G, Cirelli, S, Dormal, P, Lerut, P, Thues, E, Coutts, S, Demchuk, A, Hill, M, Hudon, M, Klein, G, Mcclelland, M, Morrish, W, Samis, G, Sutherland, G, Watson, T, Wong, J, Liu, B, Liu, Cw, Barankova, L, Chlouba, V, Fiedler, J, Priban, V, Sterba, L, Kalabova, L, Kriz, Z, Krupa, P, Privara, M, Reif, M, Souckova, L, Staffa, R, Vlachovsky, R, Vojtisek, B, Hrbac, T, Kuliha, M, Prochazka, V, Roubec, M, Skoloudik, D, Abd Allah, F, Eldessoki, Mh, Kassem, Hh, Gharieb, Hs, Cardon, Jm, Le Gallou Wittenberg, A, Allaire, E, Becquemin, Jp, Cochennec, F, Desgranges, P, Hosseini, H, Kobeiter, H, Marzelle, J, Bergeron, P, Padovani, R, Trastour, Jc, Biermaier, B, Gissler, Hm, Klotzsch, C, Pfeiffer, T, Schneider, R, Soehl, L, Wennrih, M, Botsios, S, Branzan, D, Braunlich, S, Holzer, H, Lenzer, J, Reichenbecher, C, Piorkowski, C, Schuster, J, Scheinert, D, Schmidt, A, Ulrich, M, Werner, M, Coster, A, Engelhardt, A, Ratusinski, Cm, Berekoven, B, Frerker, K, Gordon, V, Bellenis, I, Polydorou, A, Polydorou, V, Tavernarakis, A, Ioannou, N, Terzoudi, M, Chatzinikou, E, Giannoukas, A, Hadjigeorgiou, G, Koutsias, S, Ralli, S, Rousas, N, Nemes, B, Jàrànyi, Z, Szabo, A, Varga, D, Barzo, P, Bodosi, M, Fako, E, Fulop, B, Kuncz, A, Nagy, E, Nemeth, T, Pazdernyik, S, Skoba, K, Voros, E, Haider, Sn, Harbison, J, Madhavan, P, Moore, D, Beyar, R, Hoffman, A, Karram, T, Kerner, A, Nikolsky, E, Nitecki, S, Amatucci, G, Vittorio, P, Frederico, Marinazzo, D, Regina, G, Giaquinta, A, Patti, F, Veroux, M, Veroux, P, Adobbati, L, Bertoni, G, Bianchi, P, Cireni, L, Martello, L, Arcuri, L, Casoni, F, Coppi, G, Moratto, R, Veronesi, J, Bajardi, G, Savettieri, G, Corbetta, R, Odero, A, Quaretti, P, Thyrion, Z, Cao, P, Caso, V, Derango, P, Farchioni, L, Parlani, G, Malferrari, G, Strozzi, F, Vecchiati, E, Biello, Antonella, Capoccia, Laura, Menna, Danilo, Rizzo, ANNA RITA, Sbarigia, Enrico, Speziale, Francesco, Toni, D, Giovanni, M, Meola, G, Nano, G, Occiuto, Mt, Stegher, S, Tealdi, D, Accrocca, F, Ambrogi, C, Barbazza, R, Marcucci, G, Cappelli, A, de Donato, G, Palasciano, G, Pieragalli, D, Setacci, C, Settaci, F, Labate, C, Ferrero, E, Ferri, M, Viazzo, A, Castelli, P, Delodovici, Ml, Ferrario, M, Piffaretti, G, Tomei, G, Furui, E, Inoue, T, Kondo, R, Matsumoto, Y, Shimizu, H, Aidashova, B, Kospanov, N, Lyssenko, R, Mussagaliev, D, De Borst GJ, Den Hartog AG, Lo, R, Moll, F, Toorop, R, Van Der Worp HB, Vonken, Ej, Bakke, S, Krohg Sorensen, K, Skjelland, M, Andziak, P, Drelichowski, S, Dratwicki, M, Gil, R, Iwanowski, W, Koncewicz, K, Nowicki, M, Pniewski, J, Rzezak, J, Seweryniak, P, Bialek, P, Biejat, Z, Czepel, W, Czlonkowska, A, Dowzenko, A, Jedzrejewska, J, Kobayashi, A, Leszezyuski, J, Malek, A, Polanski, J, Proczka, R, Skorski, M, Szostek, M, Aleksic, N, Babic, S, Kolar, J, Sagic, D, Tanaskovic, S, Colic, M, Jovanovic, D, Koncar, I, Bartko, D, Beno, P, Rusnak, F, Zelenak, K, Gasparini, M, Grad, A, Kompara, I, Milosevic, Z, Flis, V, Matela, J, Miksic, K, Milotic, F, Mrdja, B, Stirn, B, Tetickovic, E, Chamorro, A, Obach, V, Riambau, V, Roman, S, Blanco, E, Izquierdo, Ay, Guerra, M, Campbell, E, Lindgren, H, Nyberg, J, Plate, G, Parsson, H, Qvarfordt, P, Acosta, S, Brandt, K, Dias, N, Gottsater, A, Holst, J, Kristmundsson, T, Kuhme, T, Kolbel, T, Lindblad, B, Lindh, M, Malina, M, Ohrlander, T, Resch, T, Rönnle, V, Sonesson, B, Warvsten, M, Zdanowski, Z, Bengt, B, Delle, M, Formgren, J, Jarl, L, Kall, Tb, Konrad, P, Nyman, N, Skioldebrand, C, Steuer, J, Takolander, R, Ahlhelm, Fj, Bonati, L, Engelter, Ss, Eugster, T, Gensicke, H, Lyrer, P, Mariani, L, Stierli, P, Stippich, C, Wolff, T, Brown, E, Butler, N, Day, Dj, Hayes, P, Higgins, N, Jumilla, E, Martin, P, Mitchell, J, Varty, K, Birt, A, Davies, P, George, J, Graham, A, Jonker, L, Joseph, T, Kelsall, N, Potts, C, Wilson, T, Davey, P, Hayman, R, Tervitt, G, Abdul Hamiq, A, Bryce, J, Chetter, I, Ettles, D, Lakshminarayan, R, Mitchelsonm, K, Rhymes, C, Robinson, G, Scott, P, Vickers, A, Baht, H, Balogun, I, Burger, I, Cowie, L, Gunathilagan, G, Hargroves, D, Insall, R, Jones, S, Rudenko, H, Senaratne, J, Thomas, G, Thomson, A, Enevoldson, P, Nahser, H, O'Brian, I, Torella, F, Watling, D, White, R, Clifton, A, Eley, C, Khanom, N, O'Reilly, J, Pereira, A, Bicknell, C, Cheshire, N, Gibbs, R, Hamady, M, James, A, Jenkins, M, Lacey, A, Mireskandari, M, Sachs, T, Wolfe, J, Hardy, D, Justin, F, Phiri, L, Sekaran, L, Sethuraman, S, Tate, L, Akyea Mensah, J, Chrisopoulou, A, Smyth, Jv, Nichol, I, Parry, A, Young, G, Clarke, M, Davis, M, Dixit, A, Dyker, A, Ford, G, Jackson, R, Kappadath, S, Lambert, D, Lees, T, Louw, S, Parr, N, Stansby, G, Wales, L, Wealleans, V, Wilson, L, Wyatt, M, Dorman, P, Hughes, A, Jones, D, Mendelow, Ad, Rodgers, H, Macsweeney, S, Mcconachie, N, Southam, A, Sunman, W, Briley, D, Darby, C, Handa, A, Hands, L, Kuker, W, Michael, K, Perkins, J, Schulz, U, Smith, D, Teal, R, Donnelly, M, D'Souza, S, Asehosem Egun, A, Gregory, B, Kelly, C, Punekar, S, Raj, S, Seriki, D, Thomson, G, Beard, J, Cleveland, T, Humphreys, J, Jenkins, A, King, C, Lonsdale, R, Nair, R, Nawaz, S, Okhuoya, F, Turner, D, Venables, G, Brown, J, Durairajan, R, Guyler, P, Harman, P, Jakeways, M, Khuoge, C, Kundu, A, Loganathan, T, Sinha, D, Thompson, V, Tysoe, S, Barer, Brown, A, Crawford, S, Dunlop, P, Majmudar, Mitchell, D, O'Brien, O'Connell, Scott, Vetrivel, S, Ashleigh, R, Butterfield, S, Gamble, G, Ghosh, J, Mccollum, C, Welch, M, Welsh, S, Kazan, V, Nazzal, M, Ramsey Williams, V, Halliday, A, Davies, C, Peto, R, Gray, A, Mihaylova, B, Potter, J, Flather, M, Mansfield, A, Farrell, B, Rahimi, K, Simpson, D, Thomas, D, Gough, M, Rothwell, P, Giles, M, Leopold, P, Belli, A, Sandercock, P, Gray, R, Shearman, C, Molyneux, A, Hayter, E, Lay, M, Munday, A, Young, A, Delmestri, A., Halliday, A, Bulbulia, R, Gray, W, Naughten, A, den Hartog, A, Delmestri, A, Wallis, C, le Conte, S, Macdonald, S, Tolva, V, Cras, Patrick, Hendriks, Jeroen, Lauwers, Patrick, van Schil, Paul, ACST-2 Collaborative Group, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - SSS/IREC/IMAG - Pôle d'imagerie médicale, UCL - (SLuc) Service de chirurgie cardiovasculaire et thoracique, UCL - (SLuc) Service de radiologie, and UCL - (SLuc) Service de neurologie

Subjects
Male, Time Factors, Carotid artery stenosis, Carotid artery stenting, Carotid endarterectomy, Randomized controlled trial, Stroke, medicine.medical_treatment, Myocardial Infarction, Severity of Illness Index, law.invention, law, Risk Factors, MED/22 - CHIRURGIA VASCOLARE, Carotid Stenosis, Endarterectomy, Endarterectomy, Carotid, Middle Aged, Treatment Outcome, Female, Stents, medicine.symptom, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Aged, Angioplasty, Asymptomatic Diseases, Cardiovascular Agents, Humans, Patient Selection, Risk Assessment, Asymptomatic, medicine, Carotid, business.industry, Vascular surgery, medicine.disease, Surgery, Cardiovascular agent, Human medicine, business
Abstract

Objectives: ACST-2 is currently the largest trial ever conducted to compare carotid artery stenting (CAS) with carotid endarterectomy (CEA) in patients with severe asymptomatic carotid stenosis requiring revascularization. Methods: Patients are entered into ACST-2 when revascularization is felt to be clearly indicated, when CEA and CAS are both possible, but where there is substantial uncertainty as to which is most appropriate. Trial surgeons and interventionalists are expected to use their usual techniques and CE-approved devices. We report baseline characteristics and blinded combined interim results for 30-day mortality and major morbidity for 986 patients in the ongoing trial up to September 2012. Results: A total of 986 patients (687 men, 299 women), mean age 68.7 years (SD ± 8.1) were randomized equally to CEA or CAS. Most (96%) had ipsilateral stenosis of 70-99% (median 80%) with contralateral stenoses of 50-99% in 30% and contralateral occlusion in 8%. Patients were on appropriate medical treatment. For 691 patients undergoing intervention with at least 1-month follow-up and Rankin scoring at 6 months for any stroke, the overall serious cardiovascular event rate of periprocedural (within 30 days) disabling stroke, fatal myocardial infarction, and death at 30 days was 1.0%. Conclusions: Early ACST-2 results suggest contemporary carotid intervention for asymptomatic stenosis has a low risk of serious morbidity and mortality, on par with other recent trials. The trial continues to recruit, to monitor periprocedural events and all types of stroke, aiming to randomize up to 5,000 patients to determine any differential outcomes between interventions. Clinical trial: ISRCTN21144362. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Published
2016

5. Outcome of Surgical or Endovascular Treatment of Giant Intracranial Aneurysms, with Emphasis on Age, Aneurysm Location, and Unruptured Aneuryms - A Systematic Review and Meta-Analysis

Author

Dengler, Julius, Maldaner, Nicolai, Maldaner, N., van der Zwan, A., van Doormaal, T., Cognard, C., Gawlitza, M., Walter, J., Kalff, R., Fiedler, J., Uebelacker, A., Dengler, J., Bohner, G., Wiener, E., Bauknecht, H. C., Heuschmann, P. U., Malzahn, U., Gläsker, S., Zentner, J., Gläsker, Sven, Van Velthoven, V., Guhl, S., Schroeder, H. W. S., Strowitzki, M., Etminan, N., Haengghi, D., Eicker, S., Turowski, B., Schebesch, K. M., Brawanski, A., Endres, Matthias, Wrede, K., Sure, U., Schmidt, N. O., Regelsberger, J., Westphal, M., Mielke, D., Rohde, V., Hosch, H., Moskopp, D., Joedicke, A., Wagner, Martin, Hohaus, C., Meisel, H. J., Wostrack, M., Meyer, B., Lehmberg, J., Musahl, C., Hopf, N., Winkler, G., Spetzger, U., Graewe, A., Malzahn, Uwe, Meier, U., Hong, B., Nakamura, M., Krauss, J., Grote, A., Simon, M., Schramm, J., Kursumovic, A., Rath, S. A., Marbacher, S., Heuschmann, Peter U, Fathi, A., Fandino, J., Familiari, P., Raco, A., Bijlenga, P., Schaller, K., Gruber, A., Wang, W. T., Knosp, E., Hoffmann, K. T., Vajkoczy, Peter, Boxhammer, E., Rüfenacht, D. A., Wanke, I., Boccardi, E., Piano, M., Niemelä, M., Nurminen, V., Lehecka, M., Hernesniemi, J., Burkhardt, J. K., Group, Giant Intracranial Aneurysm Study, Bozinov, O., Regli, L., Shekhtman, O. D., Eliava, S. S., Kato, N., Irie, K., Nishimura, K., Kaku, S., Arakawa, H., Yuki, I., Vajkoczy, P., Ishibashi, T., Murayama, Y., Fiss, I., Kombos, T., Pedro, M. T., König, R., Wirtz, R., Brand, C., Hagel, V., Helthuis, J., Surgical clinical sciences, University of Zurich, and Dengler, Julius

Subjects
methods [Embolization, Therapeutic], medicine.medical_treatment, Review, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, Medicine, Giant intracranial aneurysm, Embolization, Research Support, Non-U.S. Gov't, surgery [Intracranial Aneurysm], Embolization, Therapeutic, 2728 Neurology (clinical), Treatment Outcome, Neurology, Endovascular procedures, Meta-analysis, Internal carotid artery, Therapeutic, Cardiology and Cardiovascular Medicine, Carotid Artery, Internal, medicine.medical_specialty, pathology [Intracranial Aneurysm], Surgical aneurysm treatment, MEDLINE, 610 Medicine & health, surgery [Carotid Artery, Internal], 2705 Cardiology and Cardiovascular Medicine, 03 medical and health sciences, 10180 Clinic for Neurosurgery, Aneurysm, medicine.artery, Humans, Endovascular treatment, ddc:610, Retrospective Studies, business.industry, Retrospective cohort study, Intracranial Aneurysm, medicine.disease, Internal, Surgery, ddc:616.8, Clinical trial, meta-analysis, pathology [Carotid Artery, Internal], 2808 Neurology, Endovascular Procedures, Neurology (clinical), Carotid Artery, business, 030217 neurology & neurosurgery, methods [Endovascular Procedures]
Abstract

Background: Designing treatment strategies for unruptured giant intracranial aneurysms (GIA) is difficult as evidence of large clinical trials is lacking. We examined the outcome following surgical or endovascular GIA treatment focusing on patient age, GIA location and unruptured GIA. Methods: Medline and Embase were searched for studies reporting on GIA treatment outcome published after January 2000. We calculated the proportion of good outcome (PGO) for all included GIA and for unruptured GIA by meta-analysis using a random effects model. Results: We included 54 studies containing 64 study populations with 1,269 GIA at a median follow-up time (FU-T) of 26.4 months (95% CI 10.8-42.0). PGO was 80.9% (77.4-84.4) in the analysis of all GIA compared to 81.2% (75.3-86.1) in the separate analysis of unruptured GIA. For each year added to patient age, PGO decreased by 0.8%, both for all GIA and unruptured GIA. For all GIA, surgical treatment resulted in a PGO of 80.3% (95% CI 76.0-84.6) compared to 84.2% (78.5-89.8, p = 0.27) after endovascular treatment. In unruptured GIA, PGO was 79.7% (95% CI 71.5-87.8) after surgical treatment and 84.9% (79.1-90.7, p = 0.54) after endovascular treatment. PGO was lower in high quality studies and in studies presenting aggregate instead of individual patient data. In unruptured GIA, the OR for good treatment outcome was 5.2 (95% CI 2.0-13.0) at the internal carotid artery compared to 0.1 (0.1-0.3, p < 0.1) in the posterior circulation. Patient sex, FU-T and prevalence of ruptured GIA were not associated with PGO. Conclusions: We found that the chances of good outcome after surgical or endovascular GIA treatment mainly depend on patient age and aneurysm location rather than on the type of treatment conducted. Our analysis may inform future research on GIA.

Published
2016

6. Perianeurysmal edema in giant intracranial aneurysms in relation to aneurysm location, size, and partial thrombosis

Author

Dengler, Julius, Maldaner, Nicolai, Bijlenga, Philippe, Burkhardt, Jan-Karl, Graewe, Alexander, Guhl, Susanne, Hong, Bujung, Hohaus, Christian, Kursumovic, Adisa, Mielke, Dorothee, Schebesch, Karl-Michael, Wostrack, Maria, Rufenacht, Daniel, Vajkoczy, Peter, Schmidt, Nils Ole, Vajkoczy, P, Maldaner, N, Uebelacker, A, Dengler, J, Endres, M, Bohner, G, Wiener, E, Bauknecht, H C, Heuschmann, P U, Malzahn, U, Gläsker, S, Zentner, J, Van Velthoven, V, Guhl, S, Schroeder, Werner, Strowitzki, M, Etminan, N, Haengghi, D, Eicker, S, Turowski, B, Schebesch, K M, Brawanski, A, Wrede, Karsten, Sure, Ulrich, Schmidt, N O, Regelsberger, J, Westphal, M, Mielke, D, Rohde, V, Hosch, H, Moskopp, D, Joedicke, A, Hohaus, C, Meisel, H J, Wostrack, M, Meyer, B, Lehmberg, J, Musahl, C, Hopf, N, Winkler, G, Spetzger, U, Graewe, A, Meier, U, Hong, B, Nakamura, M, Krauss, J, Grote, A, Simon, M, Schramm, J, Kursumovic, A, Rath, S A, Marbacher, S, Fathi, A, Fandino, J, Familiari, P, Raco, A, Bijlenga, P, Schaller, K, Gruber, A, Wang, W T, Knosp, E, Hoffmann, K T, Boxhammer, E, Rüfenacht, Daniel, Boccardi, E, Piano, M, Niemelä, M, Nurminen, V, Lehecka, M, Hernesniemi, J, Burkhardt, J K, Bozinov, O, Regli, L, Shekhtman, O D, Eliava, S S, Kato, N, Irie, K, Nishimura, K, Kaku, S, Arakawa, H, Yuki, I, Ishibashi, T, Murayama, Y, Fiss, I, Kombos, T, Pedro, M T, König, R, Wirtz, R, Helthuis, J, van der Zwan, A, Cognard, C, Gawlitza, M, Wanke, Isabel, Fiedler, J, Surgical clinical sciences, University of Zurich, and Dengler, Julius

Subjects
Aneurysm volume, Adult, Male, medicine.medical_specialty, animal structures, Perianeurysmal edema, Clinical Neurology, Medizin, 610 Medicine & health, Brain Edema, Giant intracranial aneurysm, Partially thrombosed aneurysm, Vascular disorders, Aged, Female, Humans, Intracranial Aneurysm, Magnetic Resonance Imaging, Middle Aged, Retrospective Studies, Thrombosis, Surgery, Medicine (all), Neurology (clinical), Imaging data, 10180 Clinic for Neurosurgery, Aneurysm, medicine.artery, Edema, medicine, 10. No inequality, medicine.diagnostic_test, business.industry, Research Support, Non-U.S. Gov't, Magnetic resonance imaging, medicine.disease, 2746 Surgery, ddc:616.8, Giant Intracranial Aneurysm, 2728 Neurology (clinical), Middle cerebral artery, Radiology, Internal carotid artery, medicine.symptom, business, Partial thrombosis
Abstract

OBJECT The underlying mechanisms causing intracranial perianeurysmal edema (PAE) are still poorly understood. Since PAE is most frequently observed in giant intracranial aneurysms (GIAs), the authors designed a study to examine the occurrence of PAE in relation to the location, size, and partial thrombosis (PT) of GIAs along with the clinical impact of PAE. METHODS Magnetic resonance imaging data for patients with a diagnosis of unruptured GIA from the international multicenter Giant Intracranial Aneurysm Registry were retrospectively analyzed with regard to location and size of the GIA, PAE volume, and the presence of PT. The occurrence of PAE was correlated to clinical findings. RESULTS Imaging data for 69 GIAs were eligible for inclusion in this study. Perianeurysmal edema was observed in 33.3% of all cases, with the highest frequency in GIAs of the middle cerebral artery (MCA; 68.8%) and the lowest frequency in GIAs of the cavernous internal carotid artery (ICA; 0.0%). Independent predictors of PAE formation were GIA volume (OR 1.13, p = 0.02) and the occurrence of PT (OR 9.84, p = 0.04). Giant intracranial aneurysm location did not predict PAE occurrence. Giant aneurysms with PAE were larger than GIAs without PAE (p < 0.01), and GIA volume correlated with PAE volume (rs = 0.51, p = 0.01). Perianeurysmal edema had no influence on the modified Rankin Scale score (p = 0.30 or the occurrence of aphasia (p = 0.61) or hemiparesis (p = 0.82). CONCLUSIONS Perianeurysmal edema was associated with GIA size and the presence of PT. As no PAE was observed in cavernous ICA aneurysms, even though they exerted mass effect on the brain and also displayed PT, the dura mater may serve as a barrier protecting the brain from PAE formation.

Published
2015

7. Interferon β-1b-neutralizing antibodies 5 years after clinically isolated syndrome

Author

Hartung, Hp, Strasser Fuchs, S, Berger, T, Vass, K, Sindic, C, Dubois, B, Dive, D, Debruyne, J, Metz, L, Rice, G, Duquette, P, Lapierre, Y, Freedman, M, Traboulsee, A, O'Connor, P, Stourac, P, Taláb, R, Zapletalová, O, Kováøová, I, Medová, E, Fiedler, J, Frederiksen, J, Brochet, B, Moreau, T, Vermersch, P, Pelletier, J, Edan, G, Clanet, M, Clavelou, P, Lebrun Frenay, C, Gout, O, Kallela, M, Pirttilä, T, Ruutiainen, J, Koivisto, K, Reunanen, M, Elovaara, I, Villringer, A, Altenkirch, H, Wessel, K, Steinke, W, Kölmel, H, Oschmann, P, Diem, R, Dressel, A, Hoffmann, F, Baum, K, Jung, S, Petereit, Hf, Reske, D, Sailer, M, Köhler, J, Sommer, N, Hohlfeld, R, Henn, Kh, Steinbrecher, A, Tumani, H, Gold, R, Rieckmann, P, Komoly, R, Gács, G, Jakab, G, Csiba, L, Vécsei, L, Miller, A, Karussis, D, Chapman, J, Ghezzi, A, Comi, G, Gallo, Paolo, Cosi, V, Durelli, L, Anten, B, Visser, L, Myhr, Km, Szczudlik, A, Selmaj, K, Stelmasiak, Z, Podemski, R, Maciejek, Z, Cunha, L, Sega Jazbec, S, Montalba, X, Arbizu, T, Saiz, A, Bárcena, J, Arroyo, R, Fernández, O, Izquierdo, G, Casanova, B, Lycke, J, Kappos, L, Mattle, H, Beer, K, Coleman, R, Chataway, J, O'Riordan, J, Howell, S. ., Neurology, Radiology and nuclear medicine, NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, and UCL - (SLuc) Service de neurologie

Subjects
Multiple Sclerosis, Injections, Subcutaneous, Relapse rate, Brain mri, Medicine, Humans, Longitudinal Studies, Prospective Studies, Clinically isolated syndrome, biology, business.industry, Immunogenicity, Interferon-beta, Antibodies, Neutralizing, Titer, Interferon β 1b, Cross-Sectional Studies, Immunology, biology.protein, Neurology (clinical), Antibody, business, Demyelinating Diseases, Follow-Up Studies, Interferon beta-1b
Abstract

To determine the frequency and consequences of neutralizing antibodies (NAbs) in patients with a first event suggestive of multiple sclerosis (MS) treated with interferon β-1b (IFNβ-1b).In the Betaseron/Betaferon in Newly Emerging MS For Initial Treatment (BENEFIT) study, patients were randomly assigned to 250 μg IFNβ-1b (Betaferon) or placebo subcutaneously every other day for 2 years or until diagnosis of clinically definite MS (CDMS). Patients were then offered open-label IFNβ-1b for up to 5 years. NAb status was assessed every 6 months by the myxovirus protein A induction assay. A titer20 NU/mL was considered NAb-positive, with low (≥20-100 NU/mL), medium (≥100-400 NU/mL), and high (≥400 NU/mL) titer categories. Here we examine early-treated patients, who received IFNβ-1b for up to 5 years.NAbs were measured in 277 of 292 early-treated patients and detected at least once in 88 (31.8%) patients, with 53 (60.2%) reverting to NAb negativity by year 5. Time to CDMS, time to confirmed disability progression, and annualized relapse rate did not differ between NAb-positive and NAb-negative patients or between periods of NAb positivity vs NAb negativity within patients. Increases in newly active lesion number and T2 lesion volume and conversion to McDonald MS were associated with NAb positivity and were more pronounced with higher titers.Although NAb positivity was associated with increased brain MRI activity, no discernible effects on clinical outcomes were found. This finding may reflect the greater power of MRI compared with clinical outcomes to detect the treatment effects of IFNβ-1b and may also result from temporal changes in NAb titers and biology.

Published
2011

8. Supportive strategies to improve adherence to IFN β-1b in multiple sclerosis - Results of the βPlus observational cohort study

Author

Pozzilli, C, Schweikert, B, Ecari, U, Oentrich, W, Benesova, Y, Fiedler, J, Meluzinova, E, Novotna, A, Pikova, J, Albrecht, W, Altmann, N, Augspach-Hofmann, R, Berdermann-Welz, S, Blodau, A, Bode, L, Böer, A, Botzler, D, Burkhardtde Boor, E, Christopher, A, Dieler, J, Domke, S, Eckhardt, U, Eder, H, Faiss, J, Fegers, S, Franz, P, Freidel, M, Haas, J, Hackebeil, C, Helfrich, S, Herzog, S, Hofmann, W, Käfferlein, W, Kausch, U, Kaya, B, Korda, W, Krumpolt, H, Luber, G, Maier, I, Mamerow, U, Müllner, E, Niedhammer, M, Oschmann, P, Ossig, W, Peschel, S, Piepenbrock, N, Rauber, A, Rauch, G, Rohrer, G, Rosenthal, A, Rüther, K, Safavi, A, Schlote, M, Schnelzer, R, Seifert, E, Seybold, J, Siefjediers, V, Siever, A, Veit, B, Wietfeld, R, Abbasyonn, T, Abdoli, M, Abolfazli, R, Airemlou, H, Alikhani, K, Ashjazadeh, N, Ashtari, F, Azarangi, D, Azarians, S, Azimi, B, Azimian, M, Beladimoghadam, N, Chitsaz, A, Etemadyfar, M, Farhoudi, M, Fayaz Nekoo, M, Ghadiri, F, Ghazvinian, S, Ghelich Nia Emrani, H, Ghorbani, A, Harirchian, M. H, Homam, M, Ilkhani, M, Khosravi, K, Lotfi, J, Malekzadeh, G, Moshiri, Z, Motamadi, M, Motamed, M. M, Nabavi, S, Nafissi, S, Najlerahim, A, Nikanfar, M, Nikkhah, K, Nikseresht, A, Noorian, A, Oraki, Z, Pashapour, A, Pourmahmoudian, H, Saadatnia, M, Sadeghi, H, Sadreddini, S, Saeidi, M, Sahraian, M, Salarjan, B, Sasannezhad, P, Seifi, J, Shahbeigi, S, Shahidi, M, Shariat, A, Shaygannejad, V, Tabatabaei, M, Togha, M, Torabi, H, Vosooghi, R, Yousefi Azarfam, J, Yousefipour, G, Block, I, Karni, A, Karussis, D, Kirshner, I, Miller, A, Milo, R, Amato, M, Annunziata, P, Assetta, M, Batocchi, A, Brescia Morra, V, Carbonin, C, Carolei, A, Catalan, M, Cavallo, R, Comi, G, Coniglio, M, Constantino, F, Costantino, C, Cottone, S, Durelli, L, Ferraro, E, Ghezzi, A, Gometto, B, Grasso, M, Greco, L, Handouk, Y, Iudice, A, Koudriautseva, T, Lugaresi, A, Maimone, D, Mannu, L, Marchioretto, F, Marrosu, M, Meola, G, Millefiorini, E, Montanari, E, Patti, F, Pauri, F, Plewnia, K, Protti, A, Reggio, A, Rottoli, M, Sinisi, L, Spitaleri, D, Tola, M. R, Abdallah, H, Eid, H, Ezzeddine, F, Jbelly, S, Khamis, C, Koussa, S, Masri, W, Sawaya, R, Serhan, A, Shatila, A. R, Souklawi, K, Sukkari, R, Tfaily, H, Traboulsi, H, Wehbi, M, Yamout, B, Hadich, M. S, Baal, M. G, Dellemyn, P, Driesen, J. J. M, Timmerhues, T. P. J, Valente, I, Abduljabar, M, Cho, K. H, Kim, J. W, Sangdoe, Y, Batue, J, Ramio, L, Benrabah, R, Couur, B, D'Gal, O, Gras, P, Guinot, H, Lemarquis, P, Munoz-Lacoste, P, Nayef, A, Vaunaize, J, Visy, J. -M, Vongsouthi, C, Chang, W. N, Tain-Junn, C, Yeh, S. J, Celebi, A, Erdemoglu, A. K, Gedizlioglu, M, Uysal Tan, F, Pozzilli C, Schweikert B, Ecari U, Oentrich W, BetaPlus Study group, Lugaresi A, Pozzilli, C, Schweikert, B, Ecari, U, Oentrich, W, and BRESCIA MORRA, Vincenzo

Subjects
Adult, Male, medicine.medical_specialty, Coping (psychology), Health outcomes, Medication Adherence, Cohort Studies, Multiple sclerosis, Adjuvants, Immunologic, Autoinjector, medicine, Humans, Prospective Studies, nurses, adherence, interferon beta-1b, multiple sclerosis, coping styles, autoinjector devices, business.industry, Interferon beta-1b, Interferon-beta, interferon beta, adherence, injection device, Middle Aged, medicine.disease, Patient support, Settore MED/26 - NEUROLOGIA, Disease factors, Neurology, Physical therapy, Female, Neurology (clinical), business, Cohort study
Abstract

Background: Low adherence to treatment in Multiple Sclerosis (MS) has been shown to lead to poor health outcomes. Various strategies to improve adherence have been suggested including educative programs, injection devices and dedicated nurse assistance. Objective: To assess the impact of elements of the patient support program on adherence; to explore disease factors affecting adherence; and to determine whether these factors influence the choices of supportive elements. Methods: A prospective, observational cohort study was conducted. MS patients were eligible if they had switched to Interferon beta-1b (IFNB-1b) between 1 and 3 months prior to inclusion. Data were collected at months 6, 12, 18 and 24 after inclusion. Adherence was defined as completion of both study protocol and medication at 24 months. Patients underwent evaluations of disability, quality of life, depression, and coping styles. Results: A total of 1077 patients from 15 countries were included, of which 61.8% were adherent to IFNB-1b after 24-months. Depression, quality of life and autoinjector devices were baseline predictors of adherence at 24-months. Coping styles did not show to have substantial impact on adherence. Lower quality of life increased the probability of choosing supportive elements. Conclusion: The study showed that the usage of autoinjector devices chosen during the study was the strongest predictor of drug adherence of all the supportive elements tested in this study. (C) 2011 Elsevier B.V. All rights reserved.

Published
2011

9. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial

Author

Strasser Fuchs, S, Berger, T, Vass, K, Sindic, C, Dubois, B, Dive, D, Debruyne, J, Metz, L, Rice, G, Duquette, P, Lapierre, Y, Freedman, M, Traboulsee, A, O'Connor, P, Stourac, P, Taláb, R, Zapletalová, O, Kovárová, I, Medová, E, Fiedler, J, Frederiksen, J, Brochet, B, Moreau, T, Vermersch, P, Pelletier, J, Edan, G, Clanet, M, Clavelou, P, Lebrun Frenay, C, Gout, O, Kallela, M, Pirttilä, T, Ruutiainen, J, Koivisto, K, Reunanen, M, Elovaara, I, Villringer, A, Altenkirch, H, Wessel, K, Hartung, Hp, Steinke, W, Kölmel, H, Oschmann, P, Diem, R, Dressel, A, Hoff, F, Baum, K, Jung, S, Felicitas Petereit, H, Reske, D, Sailer, M, Köhler, J, Sommer, N, Hohlfeld, R, Henn, Kh, Steinbrecher, A, Tumani, H, Gold, R, Rieckmann, P, Komoly, R, Gács, G, Jakab, G, Csiba, L, Vécsei, L, Miller, A, Karussis, D, Chapman, J, Ghezzi, A, Comi, G, Gallo, Paolo, Cosi, V, Durelli, L, Anten, B, Visser, L, Myhr, Km, Szczudlik, A, Selmaj, K, Stelmasiak, Z, Podemski, R, Maciejek, Z, Cunha, L, Sega Jazbec, S, Montalbán, X, Arbizu, T, Saiz, A, Bárcena, J, Arroyo, R, Fernández, O, Izquierdo, G, Casanova, B, Lycke, J, Kappos, L, Mattle, H, Beer, K, Coleman, R, Chataway, J, O'Riordan, J, Howell, S, Miller, Dh, Polman, Ch, Bauer, L, Ghazi, M, Pohl, C, Sandbrink, R, Barkhof, F, Uitdehaag, B, de Vera, A, Wu, S, Radü, Ew, Mcfarland, Hf, Kesselring, J, Petkau, Aj, Toyka, K. V., Dubois, Bénédicte, Neurology, Radiology and nuclear medicine, NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Adult, Male, Questionnaires, medicine.medical_specialty, Multiple Sclerosis, Kaplan-Meier Estimate, Placebo, Risk Assessment, Young Adult, Disability Evaluation, Double-Blind Method, Surveys and Questionnaires, Internal medicine, medicine, Humans, Proportional Hazards Models, Intention-to-treat analysis, Expanded Disability Status Scale, Clinically isolated syndrome, business.industry, Multiple sclerosis, Interferon beta-1b, Hazard ratio, Interferon-beta, medicine.disease, Magnetic Resonance Imaging, Surgery, Tolerability, Data Interpretation, Statistical, Disease Progression, Female, Neurology (clinical), business
Abstract

BACKGROUND: The Betaferon/Betaseron in newly emerging multiple sclerosis for initial treatment (BENEFIT) trial investigated the effect of treatment with interferon beta-1b after a clinically isolated syndrome. The 5-year active treatment extension compares the effects of early and delayed treatment with interferon beta-1b on time to clinically definite multiple sclerosis (CDMS) and other disease outcomes, including disability progression. METHODS: Patients with a first event suggestive of multiple sclerosis and a minimum of two clinically silent lesions in MRI were randomly assigned to receive interferon beta-1b 250 microg (n=292; early treatment) or placebo (n=176; delayed treatment) subcutaneously every other day for 2 years, or until diagnosis of CDMS. All patients were then eligible to enter a prospectively planned follow-up phase with open-label interferon beta-1b up to a maximum of 5 years after randomisation. Patients and study personnel remained unaware of initial treatment allocation throughout the study. Primary endpoints were time to CDMS, time to confirmed disability progression measured with the expanded disability status scale, and the functional assessment of multiple sclerosis trial outcomes index (FAMS-TOI) at 5 years. Analysis of the primary endpoints was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00185211. FINDINGS: 235 (80%) patients from the early treatment and 123 (70%) from the delayed treatment group completed the 5-year study. Early treatment reduced the risk of CDMS by 37% (hazard ratio [HR] 0.63, 95% CI 0.48-0.83; p=0.003) compared with delayed treatment. The risk for confirmed disability progression was not significantly lower in the early treatment group (0.76, 0.52-1.11; p=0.177). At 5 years, median FAMS-TOI scores were 125 in both groups. No significant differences in other disability related outcomes were recorded. Frequency and severity of adverse events remained within the established safety and tolerability profile of interferon beta-1b. INTERPRETATION: Effects on the rate of conversion to CDMS and the favourable long-term safety and tolerability profile support early initiation of treatment with interferon beta-1b, although a delay in treatment by up to 2 years did not affect long-term disability outcomes. FUNDING: Bayer Schering Pharma. ispartof: The Lancet Neurology vol:8 issue:11 pages:987-997 ispartof: location:England status: published

Published
2009

10. General anaesthesia versus local anaesthesia for carotid surgery (GALA): a multicentre, randomised controlled trial

Author

GALA Trial Collaborative Group, C Lewis, S, P Warlow, C, R Bodenham, A, Colam, B, M Rothwell, P, Torgerson, D, Dellagrammaticas, D, Horrocks, M, Liapis, C, P Banning, A, Gough, M, J Gough, M, Fraser, A, Grant, S, Hunter, J, Leigh-Brown, A, Paterson, M, Soosay, V, Young, A, Williamson, A, Dean, Z, Mazzoli, T, Ricci, S, Valenti, D, Bamford, J, Beard, J, Dearden, M, Murray, G, Ruckley, V, E Norman, P, Sedivy, P, Idla, A, Schmitz-Rixen, T, Maritati, G, Bodenham, A, Cokic, N, Doppler, W, Hlatky, P, Koelblinger, C, Raith, C, Zölss, C, Dimmitt, S, Gharbi, R, Hankey, G, Maden, A, P Mwipatayi, B, Sieunarine, K, Tan, A, Turner, G, Wesseldine, A, T M, E Davis, Audzei, P, Davidovski, I, Dedul, D, Hetsiuk, A, Kornievich, S, Gao, J, Y-G, Huang, Jing, G, H, Li, Y-J, Li, Liu, B, C-W, Liu, J-D, Wu, W, Ye, C-H, Yu, Ban, T, Buljan, K, Candrlic, K, Dapic, D, Ilijasevic, M, Istvanic, T, Kovac, B, Kvolik, S, Lehner, V, Pinotic, K, Hudorović, N, Ivanec, Z, Lovricević, I, Mazul-Sunko, B, Novotny, Z, D De Syo, Vuković, V, Biebl, O, Dolecek, L, C El Samman, Kalasova, H, Kubricht, V, Matous, P, Michalek, P, Stajnrt, M, Stern, M, Svec, M, Vitasek, P, Vrzal, J, Weiss, K, Janousek, L, Kieslichova, E, Mazarova, V, Piza, P, Vychodil, P, Dulovcova, V, Fiksa, J, Hruby, J, Maresch, M, Mathias, M, Rubes, D, Tosenovsky, P, Vidim, T, Henzl, M, Riman, J, Ziegler, Z, Drabek, P, Hrbac, T, Reguli, S, Stigler, J, Bachleda, P, Drac, P, Hudecek, M, Koutna, J, Sanak, D, Utikal, P, Goldemund, D, Gregor, Z, Pavlikova, J, Podlaha, J, Privara, M, Staffa, R, Vlachovsky, R, Barankova, L, Chlouba, V, Fiedler, J, Prazak, P, Priban, V, Wierer, A, Ellervee, T, Järve, H, Sell, A, Taba, P, Kolbassov, V, Kullamaa, S, Paavel, T, Abramishvili, N, Bokuchava, M, Kachapuridze, N, Kipiani, K, Papashvili, K, Pargalava, N, Adili, F, Dietz, A, Neidhart, G, Nentwig, G, M Sitzer, O, Beno, M, Essink-Hassels, M, Lander, K, Ruemenapf, G, Breuer, P, Heldt, R, Melichar, G, Rieper, J, H Eckstein, H, Poppert, H, Schneider, G, Andrikopoulos, V, Angel, A, Bakogiannis, K, Dermitzaki, M, Georgakis, P, Lioupis, C, Maras, D, G Moulakakis, K, Sfyroeras, G, Arato, E, Gyevnar, Z, Hardi, P, Kasza, G, Kollar, L, Menyhei, G, Pal, E, Sinay, L, Verzar, Z, Volgyi, E, S Elmakias, S, Harah, E, Kristal, K, Lebi, D, Leonty, Y, Levy, D, Milo, R, Yoffe, B, Bissi, M, Cappellini, B, Cassamali, T, Corino, L, Denkewitz, T, Ghilardi, G, Massetto, N, P Di Mauro, Tommasino, C, Bartolucci, R, Buffa, V, M Corsi, F, D'Avino, E, F Di Cesare, L Di Pirro, Lappa, A, Luzzi, S, Menichetti, A, Nesi, F, Pannone, A, Picozzi, P, Pogany, G, Rabitti, G, Severi, L, Avella, R, Biandolino, P, P Giomarelli, P, R Monfregola, M, Palasciano, G, Peccianti, V, Pieragalli, D, Setacci, C, Setacci, F, Sirignano, P, Bordoni, M, Casadei, V, Cugnasca, M, A De Troia, Geremia, L, Guffanti, P, G Lo Guercio, V Maniaci, M, Mauri, Morbidelli, A, Aletta, A, Costanzo, E, D'Arrigo, G, F Di Stefano, Lomeo, A, Maugeri, S, C Monea, M, Scardavilli, G, Scolaro, A, Aloisi, P, Ciccozzi, A, Manno, M, Marrelli, A, Martinazzo, C, Mastromarino, A, Petrassi, C, Piroli, A, Spartera, C, Ventura, M, Alessandrini, F, Carissimi, C, M Centritto, E, Cinelli, G, C De Filippo, Liberatoscioli, G, Modugno, P, Rossi, M, T Attanzio, M, Bajardi, G, Bellisi, M, Machi, P, Salemi, S, Savettieri, G, A Crea, M, V di Lazzaro, Ferrante, A, Guarneri, S, Manni, R, Snider, F, Stefanuto, C, Berardi, G, Bianchi, A, Comis, M, Cumbo, P, Fadde, M, Ferrero, E, Ferri, M, Filardo, A, Gaggiano, A, Ganzaroli, M, Labate, C, Maggio, D, Mennuti, G, Minicucci, S, Musso, A, Nessi, F, Pasquino, M, Perretta, L, Piazza, S, Verdecchia, C, Viazzo, A, Antico, A, Battan, E, Ciarlo, M, Giardini, G, G Luca Iob, Marinello, C, Piccolo, D, Bove, R, Castrucci, T, Lorido, A, Sammarco, S, Bruzzone, B, Cannata, D, Colotto, P, Finocchi, C, Giudici, N, Mambrini, S, Mazzei, R, Palombo, D, Pellegrino, A, Rousas, N, Viacava, A, Ermirio, D, Faga, D, Simoni, G, Benedetti-Valentini, F, Gabrielli, R, Garofano, R, Gossetti, B, Guerricchio, R, Irace, L, Lenzi, G, Gedins, M, Kisis, K, Krievins, D, Krustina, I, Lietuvietis, E, Malina, M, Morlata, N, Rits, J, Thor, S, Ivanova, P, Kikule, I, Liepa, V, Ligers, A, Stengrevica, N, Vnukova, N, Zvirgzdins, V, P J A, M Brouwers, H Geelkerken, R, Stam, A, M A, M Simon, T den Hoed, P, Oltmans, M, Rettig, H, F Veen, H, Zuidgeest, D, Feldo, M, Kesik, J, Kobusiewicz, W, Łatkiewicz, D, Myślinski, W, Przywara, S, Terlecki, P, Wroński, J, Zubilewicz, T, Alfonso, G, Azevedo, E, R de Albuquerque, Mansilha, A, Al-Salman, M, K Aldaif, A, A Alnasr, T, A El Dawlatly, A, Elkayali, A, M Rabee, H, Chudikova, E, Chudá, I, Dulka, T, Goldenberg, Z, Lofaj, P, Pavlikova, M, Pisar, M, Sefranek, V, Slysko, R, Tomka, J, Tóthová, Z, Zita, Z, A Cairols, M, Iborra, E, Mercadal, M, Rubio, F, Canovas, D, Cobo, L, Gimenez-Gaibar, A, Gonzalez, E, Gonzalo, B, Guilera, N, Hospedales, J, J Laso, M, Perez, J, Solanich, T, Hensater, M, Karlström, L, Kjällman, L, Rosengren, L, C-A, Ewaldsson, Gillgren, P, T-B, Käll, Konrad, P, Lindkvist, M, Nilsson, L, Takolander, R, E von Zweigbergk, Cinar, B, Coruh, T, Kurc, E, Ozsoy, D, Sargin, M, Tutkavul, K, Yekeler, I, Aksoy, M, Aksoy, S, Kurtoglu, M, Arar, C, Canbaz, S, Celik, Y, Ege, T, Ketenc, S, Sunar, H, Unal, S, Asik, I, Bengisun, U, Koksoy, C, Yucemen, N, C Berridge, D, Caldicott, L, Cooper, J, Cross, M, Ford, H, Fuller, R, Gamlin, F, Homer-Vanniasinkum, S, Howell, S, Kent, P, Lumb, A, A I, D Mavor, D J, A Scott, Shah, M, Wanklyn, P, S Budd, J, Mcateer, P, Shaw, L, Dewar, R, H Lewis, M, Potter, C, Richards, H, Roberts, R, Townsend, E, Wagle, A, Woodford, P, Hall, G, Holdsworth, R, Macleod, M, Michels, L, P A, G Sandercock, Sudlow, C, Woods, A, S Abraham, J, Bukhari, M, Bush, A, Calvey, J, Chadwick, I, Krishnaprasad, K, Oldham, T, Tomlinson, M, Vickers, A, Wilson, D, Wilson, P, Greystone, S, C Grocott, E, Hayes, W, Haynes, S, Jenkins, C, Jenkins, D, Moore, W, Nyamekye, I, Overstall, P, Riseboro, S, Williams, H, Boyle, J, Duane, D, Gaunt, M, J Kirkpatrick, P, Martin, P, E Risdall, J, Scurrah, N, L Turner, C, Varty, K, T Ferguson, I, Horsfall, S, C Mitchell, D, Robinson, S, Frankel, J, E Morris, G, Phillips, M, Sansome, A, J Sparkes, D, Williams, J, Ashton, W, Baker, S, Clark, M, G Darke, S, Dunnill, R, Hargreaves, M, Jenkinson, D, Thomson, C, White, N, D Wijesinghe, L, Bapat, P, A Barrett, J, D Blair, S, Chandrasekar, R, Lawrence, G, Lowe, D, Sangster, G, Smith, M, M Van Miert, K Das, S, Malik, O, Nel, M, Rakowicz, W, Aukett, M, Carmichael, M, Colchester, A, R Taylor, P, Wood, C, Ageed, A, J Boom, S, Ghosh, S, Godfrey, J, Hewitt-Gray, J, Mcdiarmid, I, Yousif, S, Ziarkowski, A, Al-Din, A, Carpenter, M, Ch'Ng, K, J Curley, P, Davey, R, Henderson, B, F Hossain, J, D Irvine, C, Loizou, L, Main, A, Stanners, A, Muldoon, T, V Soong, C, Wiggam, I, P Armon, M, Burrows, M, Holmes, L, K Metcalf, A, Nunn, D, Abdul-Hamid, A, Akomalafe, B, Bryce, J, Chetter, I, Samaan, A, Briley, D, Collin, J, Darby, C, Dobson, M, Foex, P, Grange, C, Handa, A, Hands, L, E Higham, H, J M, T Perkins, Sear, J, Stoneham, M, Hamilton, G, Judge, C, Morris-Vincent, P, Pegg, M, A Wilson, L, I Aldoori, M, B E, A Dafalla, Kumar, N, I F, C Hay, Jefferson, P, Muir, I, Peel, W, Rutherford, J, Sathianathan, J, Wight, S, Williams, D, Wrathall, W, Bachoo, P, Brittenden, J, Counsell, C, Patey, R, Read, J, L de Cossart, K Dimitri, S, Edwards, P, Fergusson, N, Jameson, P, Somauroo, J, Taylor, V, D Aravindan, P, Brocklehurst, I, Mirza, S, N Namushi, R, O Oshodi, T, Ruff, D, A Solomon, S, Vassallo, J, Egbe, M, Halstead, G, Onwudike, M, Putland, A, Roberts, N, A Salaman, R, Watson, D, Caine, S, Day, J, Lamont, P, J Murphy, P, Smith, F, Beacham, K, J Dorman, P, Lambert, D, Rodgers, H, Collas, D, Sarin, S, Shah, J, S Baht, H, Banks, J, Cowie, L, Gunathilagan, G, Hargroves, D, Insall, R, G Smithard, D, K Chadha, D, R Pillay, W, Rashid, J, Sayles, J, Hill, S, Lawton, G, M Lloyd, C, Marsh, A, Clarke, G, J Lonsdale, R, Venables, G, Cross, R, Lord, B, Mcilmoyle, J, Y Osman, H, Robinson, J, Chant, H, Mate, A, Sim, D, Upton, P, Thomas, D, H Wolfe, J, Mccollum, C, O'Neill, P, Bernatsky, V, Bondar, L, Karpenko, A, Mamonova, M, Muz, N, and Yavorsky, V

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Carotid endarterectomy, general anesthesia, local anesthesia, carotid surgery, Anesthesia, General, law.invention, Postoperative Complications, Randomized controlled trial, law, medicine, Humans, Carotid Stenosis, General anaesthesia, general anaesthesia, Stroke, Aged, Endarterectomy, Endarterectomy, Carotid, local anaesthesia, Intention-to-treat analysis, business.industry, General Medicine, Perioperative, Vascular surgery, medicine.disease, Surgery, Anesthesia, Female, business, Anesthesia, Local
Abstract

BACKGROUND: The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery. We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easier under local anaesthesia than under general anaesthesia. METHODS: We undertook a parallel group, multicentre, randomised controlled trial of 3526 patients with symptomatic or asymptomatic carotid stenosis from 95 centres in 24 countries. Participants were randomly assigned to surgery under general (n=1753) or local (n=1773) anaesthesia between June, 1999 and October, 2007. The primary outcome was the proportion of patients with stroke (including retinal infarction), myocardial infarction, or death between randomisation and 30 days after surgery. Analysis was by intention to treat. The trial is registered with Current Control Trials number ISRCTN00525237. FINDINGS: A primary outcome occurred in 84 (4.8%) patients assigned to surgery under general anaesthesia and 80 (4.5%) of those assigned to surgery under local anaesthesia; three events per 1000 treated were prevented with local anaesthesia (95% CI -11 to 17; risk ratio [RR] 0.94 [95% CI 0.70 to 1.27]). The two groups did not significantly differ for quality of life, length of hospital stay, or the primary outcome in the prespecified subgroups of age, contralateral carotid occlusion, and baseline surgical risk. INTERPRETATION: We have not shown a definite difference in outcomes between general and local anaesthesia for carotid surgery. The anaesthetist and surgeon, in consultation with the patient, should decide which anaesthetic technique to use on an individual basis. FUNDING: The Health Foundation (UK) and European Society of Vascular Surgery.

Published
2008

11. Pregnancy-associated plasma protein A and proform eosinophilic major basic protein in the detection of different types of coronary artery disease

Author

P. Ostadal, Durdil, Alice Krebsová, Petr Hájek, Martin Malý, Houbová B, Milan Macek, Marie Hladíková, Alan D, Josef Veselka, and Fiedler J

Subjects
Adult, Male, Acute coronary syndrome, medicine.medical_specialty, Pregnancy-associated plasma protein A, Physiology, Enzyme-Linked Immunosorbent Assay, Coronary Artery Disease, medicine.disease_cause, Risk Assessment, Sensitivity and Specificity, Eosinophil Major Basic Protein, Statistics, Nonparametric, Coronary artery disease, Cohort Studies, Sex Factors, Reference Values, Internal medicine, Troponin I, medicine, Humans, Pregnancy-Associated Plasma Protein-A, cardiovascular diseases, Acute Coronary Syndrome, Protein Precursors, Aged, Aged, 80 and over, Immunoassay, business.industry, Unstable angina, ST elevation, Case-control study, Age Factors, General Medicine, Middle Aged, medicine.disease, Vulnerable plaque, ROC Curve, Case-Control Studies, Cardiology, Female, business, Biomarkers
Abstract

Kryptor system was proven to be a rapid, standard method for pregnancy-associated plasma protein A and proform eosinophilic major basic protein (PAPP-A/proMBP) complex detection in coronary artery disease (CAD). No age and/or gender differences in 51 controls and 110 stable coronary artery disease (SCAD) patients were found. SCAD patients did not differ from controls and no difference in PAPP-A/proMBP levels with regards to the number of affected vessels was found. In 21 unstable angina pectoris (UAP), in 35 without and 66 with ST elevation acute myocardial infarctions (NSTEMI, STEMI respectively) patients PAPP-A/proMBP levels were increased (P=0.004 and P

Published
2007

12. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Author

Alison Halliday, Richard Bulbulia, Leo H Bonati, Johanna Chester, Andrea Cradduck-Bamford, Richard Peto, Hongchao Pan, John Potter, Hans Henning Eckstein, Barbara Farrell, Marcus Flather, Averil Mansfield, Boby Mihaylova, Kazim Rahimi, David Simpson, Dafydd Thomas, Peter Sandercock, Richard Gray, Andrew Molyneux, Cliff P Shearman, Peter Rothwell, Anna Belli, Will Herrington, Parminder Judge, Peter Leopold, Marion Mafham, Michael Gough, Piergiorgio Cao, Sumaira MacDonald, Vasha Bari, Clive Berry, S Bradshaw, Wojciech Brudlo, Alison Clarke, Robin Cox, Susan Fathers, Kamran Gaba, Mo Gray, Elizabeth Hayter, Constance Holliday, Rijo Kurien, Michael Lay, Steffi le Conte, Jessica McManus, Zahra Madgwick, Dylan Morris, Andrew Munday, Sandra Pickworth, Wiktor Ostasz, Michiel Poorthuis, Sue Richards, Louisa Teixeira, Sergey Tochlin, Lynda Tully, Carol Wallis, Monique Willet, Alan Young, Renato Casana, Chiara Malloggi, Andrea Odero Jr, Vincenzo Silani, Gianfranco Parati, Giuseppe Malchiodi, Giovanni Malferrari, Francesco Strozzi, Nicola Tusini, Enrico Vecchiati, Gioacchino Coppi, Antonio Lauricella, Roberto Moratto, Roberto Silingardi, Jessica Veronesi, Andrea Zini, Emanuele Ferrero, Michelangelo Ferri, Andrea Gaggiano, Carmelo Labate, Franco Nessi, Daniele Psacharopulo, Andrea Viazzo, Giovanni Malacrida, Daniela Mazzaccaro, Giovanni Meola, Alfredo Modafferi, Giovanni Nano, Maria Teresa Occhiuto, Paolo Righini, Silvia Stegher, Stefano Chiarandini, Filippo Griselli, Sandro Lepidi, Fabio Pozzi Mucelli, Marcello Naccarato, Mario D'Oria, Barbara Ziani, Andrea Stella, Mortalla Dieng, Gianluca Faggioli, Mauro Gargiulo, Sergio Palermo, Rodolfo Pini, Giovanni Maria Puddu, Andrea Vacirca, Domenico Angiletta, Claudio Desantis, Davide Marinazzo, Giovanni Mastrangelo, Guido Regina, Raffaele Pulli, Paolo Bianchi, Lea Cireni, Elisabetta Coppi, Rocco Pizzirusso, Filippo Scalise, Giovanni Sorropago, Valerio Tolva, Valeria Caso, Enrico Cieri, Paola DeRango, Luca Farchioni, Giacomo Isernia, Massimo Lenti, Gian Battista Parlani, Guglielmo Pupo, Grazia Pula, Gioele Simonte, Fabio Verzini, Federico Carimati, Maria Luisa Delodovici, Federico Fontana, Gabriele Piffaretti, Matteo Tozzi, Efrem Civilini, Giorgio Poletto, Bernhard Reimers, Barbara Praquin, Sonia Ronchey, Laura Capoccia, Wassim Mansour, Enrico Sbarigia, Francesco Speziale, Pasqualino Sirignano, Danilo Toni, Roberto Galeotti, Vincenzo Gasbarro, Francesco Mascoli, Tiberio Rocca, Elpiniki Tsolaki, Giulia Bernardini, Ester DeMarco, Alessia Giaquinta, Francesco Patti, Massimiliano Veroux, Pierfrancesco Veroux, Carla Virgilio, Nicola Mangialardi, Matteo Orrico, Vincenzo Di Lazzaro, Nunzio Montelione, Francesco Spinelli, Francesco Stilo, Carlo Cernetti, Sandro Irsara, Giuseppe Maccarrone, Diego Tonello, Adriana Visonà, Beniamino Zalunardo, Emiliano Chisci, Stefano Michelagnoli, Nicola Troisi, Maela Masato, Massimo Dei Negri, Andrea Pacchioni, Salvatore Saccà, Giovanni Amatucci, Alfredo Cannizzaro, Federico Accrocca, Cesare Ambrogi, Renzo Barbazza, Giustino Marcucci, Andrea Siani, Guido Bajardi, Giovanni Savettieri, Angelo Argentieri, Riccardo Corbetta, Attilio Odero, Pietro Quaretti, Federico Z Thyrion, Alessandro Cappelli, Domenico Benevento, Gianmarco De Donato, Maria Agnese Mele, Giancarlo Palasciano, Daniela Pieragalli, Alessandro Rossi, Carlo Setacci, Francesco Setacci, Domenico Palombo, Maria Cecilia Perfumo, Edoardo Martelli, Aldo Paolucci, Santi Trimarchi, Viviana Grassi, Luigi Grimaldi, Giuliana La Rosa, Domenico Mirabella, Matteo Scialabba, Leonildo Sichel, Costantino L D'Angelo, Gian Franco Fadda, Holta Kasemi, Mario Marino, Francesco Burzotta, Francesco Alberto Codispoti, Angela Ferrante, Giovanni Tinelli, Yamume Tshomba, Claudio Vincenzoni, Deborah Amis, Dawn Anderson, Martin Catterson, Mike Clarke, Michelle Davis, Anand Dixit, Alexander Dyker, Gary Ford, Ralph Jackson, Sreevalsan Kappadath, David Lambert, Tim Lees, Stephen Louw, James McCaslin, Noala Parr, Rebecca Robson, Gerard Stansby, Lucy Wales, Vera Wealleans, Lesley Wilson, Michael Wyatt, Hardeep Baht, Ibrahim Balogun, Ilse Burger, Tracy Cosier, Linda Cowie, Gunaratnam Gunathilagan, David Hargroves, Robert Insall, Sally Jones, Hannah Rudenko, Natasha Schumacher, Jawaharlal Senaratne, George Thomas, Audrey Thomson, Tom Webb, Ellen Brown, Bernard Esisi, Ali Mehrzad, Shane MacSweeney, Norman McConachie, Alison Southam, Wayne Sunman, Ahmed Abdul-Hamiq, Jenny Bryce, Ian Chetter, Duncan Ettles, Raghuram Lakshminarayan, Kim Mitchelson, Christopher Rhymes, Graham Robinson, Paul Scott, Alison Vickers, Ray Ashleigh, Stephen Butterfield, Ed Gamble, Jonathan Ghosh, Charles N McCollum, Mark Welch, Sarah Welsh, Leszek Wolowczyk, Mary Donnelly, Stephen D'Souza, Anselm A Egun, Bindu Gregary, Thomas Joseph, Christine Kelly, Shuja Punekar, M Asad Rahi, Sonia Raj, Dare Seriki, George Thomson, James Brown, Ragunath Durairajan, Iris Grunwald, Paul Guyler, Paula Harman, Matthew Jakeways, Christopher Khuoge, Ashish Kundu, Thayalini Loganathan, Nisha Menon, Raji O Prabakaran, Devesh Sinha, Vicky Thompson, Sharon Tysoe, Dennis Briley, Chris Darby, Linda Hands, Dominic Howard, Wilhelm Kuker, Ursula Schulz, Rachel Teal, David Barer, Andrew Brown, Susan Crawford, Paul Dunlop, Ramesh Krishnamurthy, Nikhil Majmudar, Duncan Mitchell, Min P Myint, Richard O'Brien, Janice O'Connell, Naweed Sattar, Shanmugam Vetrivel, Jonathan Beard, Trevor Cleveland, Peter Gaines, John Humphreys, Alison Jenkins, Craig King, Daniel Kusuma, Ralph Lindert, Robbie Lonsdale, Raj Nair, Shah Nawaz, Faith Okhuoya, Douglas Turner, Graham Venables, Paul Dorman, Andrea Hughes, Deborah Jones, David Mendelow, Helen Rodgers, Aidas Raudoniitis, Peter Enevoldson, Hans Nahser, Imelda O'Brien, Francesco Torella, Dave Watling, Richard White, Pauline Brown, Dipankar Dutta, Lorraine Emerson, Paula Hilltout, Sachin Kulkarni, Jackie Morrison, Keith Poskitt, Fiona Slim, Sarah Smith, Amanda Tyler, Joanne Waldron, Mark Whyman, Milda Bajoriene, Lucy Baker, Amanda Colston, Bekky Eliot-Jones, Gita Gramizadeh, Catherine Lewis-Clarke, Laura McCafferty, Deborah Oliver, Debbie Palmer, Abhijeet Patil, Suzannah Pegler, Gopi Ramadurai, Aisling Roberts, Tracey Sargent, Shivaprasad Siddegowda, Ravi Singh-Ranger, Akintunde Williams, Lucy Williams, Steve Windebank, Tadas Zuromskis, Lanka Alwis, Jane Angus, Asaipillai Asokanathan, Caroline Fornolles, Diana Hardy, Sophy Hunte, Frances Justin, Duke Phiri, Marie Mitabouana-Kibou, Lakshmanan Sekaran, Sakthivel Sethuraman, Margaret L Tate, Joyce Akyea-Mensah, Stephen Ball, Angela Chrisopoulou, Elizabeth Keene, Alison Phair, Steven Rogers, John V Smyth, Colin Bicknell, Jeremy Chataway, Nicholas Cheshire, Andrew Clifton, Caroline Eley, Richard Gibbs, Mohammad Hamady, Beth Hazel, Alex James, Michael Jenkins, Nyma Khanom, Austin Lacey, Maz Mireskandari, Joanna O'Reilly, Antony Pereira, Tina Sachs, John Wolfe, Philip Davey, Gill Rogers, Gemma Smith, Gareth Tervit, Ian Nichol, Andrew Parry, Gavin Young, Simon Ashley, James Barwell, Francis Dix, Azlisham M Nor, Chris Parry, Angela Birt, Paul Davies, Jim George, Anne Graham, Leon Jonker, Nicci Kelsall, Caroline Potts, Toni Wilson, Jamie Crinnion, Larissa Cuenoud, Nikola Aleksic, Srdan Babic, Nenad Ilijevski, Đorde Radak, Dragan Sagic, Slobodan Tanaskovic, Momcilo Colic, Vladimir Cvetic, Lazar Davidovic, Dejana R Jovanovic, Igor Koncar, Perica Mutavdžic, Miloš Sladojevic, Ivan Tomic, Eike S Debus, Ulrich Grzyska, Dagmar Otto, Götz Thomalla, Jessica Barlinn, Johannes Gerber, Kathrin Haase, Christian Hartmann, Stefan Ludwig, Volker Pütz, Christian Reeps, Christine Schmidt, Norbert Weiss, Sebastian Werth, Simon Winzer, Janine Gemper, Albrecht Günther, Bianka Heiling, Elisabeth Jochmann, Panagiota Karvouniari, Carsten Klingner, Thomas Mayer, Julia Schubert, Friederike Schulze-Hartung, Jürgen Zanow, Yvonne Bausback, Franka Borger, Spiridon Botsios, Daniela Branzan, Sven Bräunlich, Henryk Hölzer, Janin Lenzer, Christopher Piorkowski, Nadine Richter, Johannes Schuster, Dierk Scheinert, Andrej Schmidt, Holger Staab, Matthias Ulrich, Martin Werner, Hermann Berger, Gábor Biró, Hans-Henning Eckstein, Michael Kallmayer, Kornelia Kreiser, Alexander Zimmermann, Bärbel Berekoven, Klaus Frerker, Vera Gordon, Giovanni Torsello, Sebastian Arnold, Cora Dienel, Martin Storck, Bernhard Biermaier, Hans Martin Gissler, Christof Klötzsch, Tomas Pfeiffer, Ralph Schneider, Leander Söhl, Michael Wennrich, Angelika Alonso, Michael Keese, Christoph Groden, Andreas Cöster, Andreas Engelhardt, Christoph-Maria Ratusinski, Bengt Berg, Martin Delle, Johan Formgren, Peter Gillgren, Lotta Jarl, Torbjörn B Kall, Peter Konrad, Niklas Nyman, Claes Skiöldebrand, Johnny Steuer, Rabbe Takolander, Jonas Malmstedt, Stefan Acosta, Katarina Björses, Kerstin Brandt, Nuno Dias, Anders Gottsäter, Jan Holst, Thorarinn Kristmundsson, Tobias Kühme, Tilo Kölbel, Bengt Lindblad, Mats Lindh, Martin Malina, Tomas Ohrlander, Tim Resch, Viola Rönnle, Björn Sonesson, Margareta Warvsten, Zbigniew Zdanowski, Erik Campbell, Per Kjellin, Hans Lindgren, Johan Nyberg, Björn Petersen, Gunnar Plate, Håkan Pärsson, Peter Qvarfordt, Pavel Ignatenko, Andrey Karpenko, Vladimir Starodubtsev, Mikhail A Chernyavsky, Maria S Golovkova, Boris B Komakha, Nikolay N Zherdev, Andrey Belyasnik, Pavel Chechulov, Dmitry Kandyba, Igor Stepanishchev, Csaba Csobay-Novák, Edit Dósa, László Entz, Balázs Nemes, Zoltán Szeberin, Pál Barzó, Mihaly Bodosi, Eniko Fákó, Béla Fülöp, Tamás Németh, Szilárd Pazdernyik, Krisztina Skoba, Erika Vörös, Eleni Chatzinikou, Athanasios Giannoukas, Christos Karathanos, Stylianos Koutsias, Georgios Kouvelos, Miltiadis Matsagkas, Styliani Ralli, Christos Rountas, Nikolaos Rousas, Konstantinos Spanos, Elias Brountzos, John D Kakisis, Andreas Lazaris, Konstantinos G Moulakakis, Leonidas Stefanis, Georgios Tsivgoulis, Spyros Vasdekis, Constantine N Antonopoulos, Ion Bellenis, Dimitrios Maras, Antonios Polydorou, Victoria Polydorou, Antonios Tavernarakis, Nikolaos Ioannou, Maria Terzoudi, Miltos Lazarides, Michalis Mantatzis, Kostas Vadikolias, Lukasz Dzieciuchowicz, Marcin Gabriel, Zbigniew Krasinski, Grzegorz Oszkinis, Fryderyk Pukacki, Maciej Slowinski, Michal-Goran Stanišic, Ryszard Staniszewski, Jolanta Tomczak, Maciej Zielinski, Piotr Myrcha, Dorota Rózanski, Stanislaw Drelichowski, Wojciech Iwanowski, Katarzyna Koncewicz, Pawel Bialek, Zbigniew Biejat, Wojciech Czepel, Anna Czlonkowska, Anatol Dowzenko, Julia Jedrzejewska, Adam Kobayashi, Jerzy Leszczynski, Andrzej Malek, Jerzy Polanski, Robert Proczka, Maciej Skorski, Mieczyslaw Szostek, Piotr Andziak, Maciej Dratwicki, Robert Gil, Miroslaw Nowicki, Jaroslaw Pniewski, Jaroslaw Rzezak, Piotr Seweryniak, Pawel Dabek, Michal Juszynski, Grzegorz Madycki, Bartosz Pacewski, Witold Raciborski, Piotr Slowinski, Walerian Staszkiewicz, Martin Bombic, Vladimír Chlouba, Jirí Fiedler, Karel Hes, Petr Koštál, Jindrich Sova, Zdenek Kríž, Mojmír Prívara, Michal Reif, Robert Staffa, Robert Vlachovský, Bohuslav Vojtíšek, Tomáš Hrbác, Martin Kuliha, Václav Procházka, Martin Roubec, David Školoudík, David Netuka, Anna Šteklácová, Vladimír Beneš III, Pavel Buchvald, Ladislav Endrych, Miroslav Šercl, Walter Campos Jr, Ivan B Casella, Nelson de Luccia, André E V Estenssoro, Calógero Presti, Pedro Puech-Leão, Celso R B Neves, Erasmo S da Silva, Cid J Sitrângulo Jr, José A T Monteiro, Gisela Tinone, Marcelo Bellini Dalio, Edwaldo E Joviliano, Octávio M Pontes Neto, Mauricio Serra Ribeiro, Patrick Cras, Jeroen M H Hendriks, Mieke Hoppenbrouwers, Patrick Lauwers, Caroline Loos, Laetitia Yperzeele, Mia Geenens, Dimitri Hemelsoet, Isabelle van Herzeele, Frank Vermassen, Parla Astarci, Frank Hammer, Valérie Lacroix, André Peeters, Robert Verhelst, Silvana Cirelli, Pol Dormal, Annelies Grimonprez, Bart Lambrecht, Philipe Lerut, Eddy Thues, Guy De Koster, Quentin Desiron, Alain Maertens de Noordhout, Danielle Malmendier, Mireille Massoz, Georges Saad, Marc Bosiers, Joren Callaert, Koen Deloose, Estrella Blanco Cañibano, Beatriz García Fresnillo, Mercedes Guerra Requena, Pilar C Morata Barrado, Miguel Muela Méndez, Antonio Yusta Izquierdo, Fernando Aparici Robles, Paula Blanes Orti, Luis García Dominguez, Rafael Martínez López, Manuel Miralles Hernández, José I Tembl Ferrairo, Ángel Chamorro, Juan Macho, Víctor Obach, Vincent Riambau, Luis San Román, Frank J Ahlhelm, Kristine Blackham, Stefan Engelter, Thomas Eugster, Henrik Gensicke, Lorenz Gürke, Philippe Lyrer, Luigi Mariani, Marina Maurer, Edin Mujagic, Mandy Müller, Marios Psychogios, Peter Stierli, Christoph Stippich, Christopher Traenka, Thomas Wolff, Benjamin Wagner, Martina M Wiegert, Sandra Clarke, Michael Diepers, Ernst Gröchenig, Philipp Gruber, Andrej Isaak, Timo Kahles, Regula Marti, Krassen Nedeltchev, Luca Remonda, Nadir Tissira, Martina Valença Falcão, Gert J de Borst, Rob H Lo, Frans L Moll, Raechel Toorop, Bart H van der Worp, Evert J Vonken, Jaap L Kappelle, Ommid Jahrome, Floris Vos, Wouter Schuiling, Hendrik van Overhagen, Rudolf W M Keunen, Bob Knippenberg, Jan J Wever, Jan W Lardenoije, Michel Reijnen, Luuk Smeets, Steven van Sterkenburg, Gustav Fraedrich, Elke Gizewski, Ingrid Gruber, Michael Knoflach, Stefan Kiechl, Barbara Rantner, Timur Abdulamit, Patrice Bergeron, Raymond Padovani, Jean-Christophe Trastour, Jean-Marie Cardon, Anne Le Gallou-Wittenberg, Eric Allaire, Jean-Pierre Becquemin, Frédéric Cochennec-Paliwoda, Pascal Desgranges, Hassan Hosseini, Hicham Kobeiter, Jean Marzelle, Mohammed A Almekhlafi, Simerpreet Bal, Phillip A Barber, Shelagh B Coutts, Andrew M Demchuk, Muneer Eesa, Michelle Gillies, Mayank Goyal, Michael D Hill, Mark E Hudon, Anitha Jambula, Carol Kenney, Gary Klein, Marie McClelland, Alim Mitha, Bijoy K Menon, William F Morrish, Steven Peters, Karla J Ryckborst, Greg Samis, Supriya Save, Eric E Smith, Peter Stys, Suresh Subramaniam, Garnette R Sutherland, Tim Watson, John H Wong, L Zimmel, Vojko Flis, Jože Matela, Kazimir Miksic, Franko Milotic, Božidar Mrdja, Barbara Stirn, Erih Tetickovic, Mladen Gasparini, Anton Grad, Ingrid Kompara, Zoren Miloševic, Veronika Palmiste, Toomas Toomsoo, Balzhan Aidashova, Nursultan Kospanov, Roman Lyssenko, Daulet Mussagaliev, Rafi Beyar, Aaron Hoffman, Tony Karram, Arthur Kerner, Eugenia Nikolsky, Samy Nitecki, Silva Andonova, Chavdar Bachvarov, Vesko Petrov, Ivan Cvjetko, Vinko Vidjak, Damir Halužan, Mladen Petrunic, Bao Liu, Chang-Wei Liu, Daniel Bartko, Peter Beno, František Rusnák, Kamil Zelenák, Masayuki Ezura, Takashi Inoue, Naoto Kimura, Ryushi Kondo, Yasushi Matsumoto, Hiroaki Shimizu, Hidenori Endo, Eisuke Furui, Søren Bakke, Kristen Krohg-Sørensen, Terje Nome, Mona Skjelland, Bjørn Tennøe, João Albuquerque e Castro, Gonçalo Alves, Frederico Bastos Gonçalves, José de Aragão Morais, Ana C Garcia, Hugo Valentim, Leonor Vasconcelos, Fernando Belcastro, Fernando Cura, Patricio Zaefferer, Foad Abd-Allah, Mohamed H Eldessoki, Hussein Heshmat Kassem, Haytham Soliman Gharieb, Mary P Colgan, Syed N Haider, Joe Harbison, Prakash Madhavan, Dermot Moore, Gregor Shanik, Viviane Kazan, Munier Nazzal, Vicki Ramsey-Williams, ACST-2 Collaborative Group, Group, ACST-2 Collaborative, Halliday A., Bulbulia R., Bonati L.H., Chester J., Cradduck-Bamford A., Peto R., Pan H., Potter J., Henning Eckstein H., Farrell B., Flather M., Mansfield A., Mihaylova B., Rahimi K., Simpson D., Thomas D., Sandercock P., Gray R., Molyneux A., Shearman C.P., Rothwell P., Belli A., Herrington W., Judge P., Leopold P., Mafham M., Gough M., Cao P., MacDonald S., Bari V., Berry C., Bradshaw S., Brudlo W., Clarke A., Cox R., Fathers S., Gaba K., Gray M., Hayter E., Holliday C., Kurien R., Lay M., le Conte S., McManus J., Madgwick Z., Morris D., Munday A., Pickworth S., Ostasz W., Poorthuis M., Richards S., Teixeira L., Tochlin S., Tully L., Wallis C., Willet M., Young A., Casana R., Malloggi C., Odero A., Silani V., Parati G., Malchiodi G., Malferrari G., Strozzi F., Tusini N., Vecchiati E., Coppi G., Lauricella A., Moratto R., Silingardi R., Veronesi J., Zini A., Ferrero E., Ferri M., Gaggiano A., Labate C., Nessi F., Psacharopulo D., Viazzo A., Malacrida G., Mazzaccaro D., Meola G., Modafferi A., Nano G., Occhiuto M.T., Righini P., Stegher S., Chiarandini S., Griselli F., Lepidi S., Pozzi Mucelli F., Naccarato M., D'Oria M., Ziani B., Stella A., Dieng M., Faggioli G., Gargiulo M., Palermo S., Pini R., Puddu G.M., Vacirca A., Angiletta D., Desantis C., Marinazzo D., Mastrangelo G., Regina G., Pulli R., Bianchi P., Cireni L., Coppi E., Pizzirusso R., Scalise F., Sorropago G., Tolva V., Caso V., Cieri E., DeRango P., Farchioni L., Isernia G., Lenti M., Parlani G.B., Pupo G., Pula G., Simonte G., Verzini F., Carimati F., Delodovici M.L., Fontana F., Piffaretti G., Tozzi M., Civilini E., Poletto G., Reimers B., Praquin B., Ronchey S., Capoccia L., Mansour W., Sbarigia E., Speziale F., Sirignano P., Toni D., Galeotti R., Gasbarro V., Mascoli F., Rocca T., Tsolaki E., Bernardini G., DeMarco E., Giaquinta A., Patti F., Veroux M., Veroux P., Virgilio C., Mangialardi N., Orrico M., Di Lazzaro V., Montelione N., Spinelli F., Stilo F., Cernetti C., Irsara S., Maccarrone G., Tonello D., Visona A., Zalunardo B., Chisci E., Michelagnoli S., Troisi N., Masato M., Dei Negri M., Pacchioni A., Sacca S., Amatucci G., Cannizzaro A., Accrocca F., Ambrogi C., Barbazza R., Marcucci G., Siani A., Bajardi G., Savettieri G., Argentieri A., Corbetta R., Quaretti P., Thyrion F.Z., Cappelli A., Benevento D., De Donato G., Mele M.A., Palasciano G., Pieragalli D., Rossi A., Setacci C., Setacci F., Palombo D., Perfumo M.C., Martelli E., Paolucci A., Trimarchi S., Grassi V., Grimaldi L., La Rosa G., Mirabella D., Scialabba M., Sichel L., D'Angelo C.L., Fadda G.F., Kasemi H., Marino M., Burzotta F., Codispoti F.A., Ferrante A., Tinelli G., Tshomba Y., Vincenzoni C., Amis D., Anderson D., Catterson M., Clarke M., Davis M., Dixit A., Dyker A., Ford G., Jackson R., Kappadath S., Lambert D., Lees T., Louw S., McCaslin J., Parr N., Robson R., Stansby G., Wales L., Wealleans V., Wilson L., Wyatt M., Baht H., Balogun I., Burger I., Cosier T., Cowie L., Gunathilagan G., Hargroves D., Insall R., Jones S., Rudenko H., Schumacher N., Senaratne J., Thomas G., Thomson A., Webb T., Brown E., Esisi B., Mehrzad A., MacSweeney S., McConachie N., Southam A., Sunman W., Abdul-Hamiq A., Bryce J., Chetter I., Ettles D., Lakshminarayan R., Mitchelson K., Rhymes C., Robinson G., Scott P., Vickers A., Ashleigh R., Butterfield S., Gamble E., Ghosh J., McCollum C.N., Welch M., Welsh S., Wolowczyk L., Donnelly M., D'Souza S., Egun A.A., Gregary B., Joseph T., Kelly C., Punekar S., Rahi M.A., Raj S., Seriki D., Thomson G., Brown J., Durairajan R., Grunwald I., Guyler P., Harman P., Jakeways M., Khuoge C., Kundu A., Loganathan T., Menon N., Prabakaran R.O., Sinha D., Thompson V., Tysoe S., Briley D., Darby C., Hands L., Howard D., Kuker W., Schulz U., Teal R., Barer D., Brown A., Crawford S., Dunlop P., Krishnamurthy R., Majmudar N., Mitchell D., Myint M.P., O'Brien R., O'Connell J., Sattar N., Vetrivel S., Beard J., Cleveland T., Gaines P., Humphreys J., Jenkins A., King C., Kusuma D., Lindert R., Lonsdale R., Nair R., Nawaz S., Okhuoya F., Turner D., Venables G., Dorman P., Hughes A., Jones D., Mendelow D., Rodgers H., Raudoniitis A., Enevoldson P., Nahser H., O'Brien I., Torella F., Watling D., White R., Brown P., Dutta D., Emerson L., Hilltout P., Kulkarni S., Morrison J., Poskitt K., Slim F., Smith S., Tyler A., Waldron J., Whyman M., Bajoriene M., Baker L., Colston A., Eliot-Jones B., Gramizadeh G., Lewis-Clarke C., McCafferty L., Oliver D., Palmer D., Patil A., Pegler S., Ramadurai G., Roberts A., Sargent T., Siddegowda S., Singh-Ranger R., Williams A., Williams L., Windebank S., Zuromskis T., Alwis L., Angus J., Asokanathan A., Fornolles C., Hardy D., Hunte S., Justin F., Phiri D., Mitabouana-Kibou M., Sekaran L., Sethuraman S., Tate M.L., Akyea-Mensah J., Ball S., Chrisopoulou A., Keene E., Phair A., Rogers S., Smyth J.V., Bicknell C., Chataway J., Cheshire N., Clifton A., Eley C., Gibbs R., Hamady M., Hazel B., James A., Jenkins M., Khanom N., Lacey A., Mireskandari M., O'Reilly J., Pereira A., Sachs T., Wolfe J., Davey P., Rogers G., Smith G., Tervit G., Nichol I., Parry A., Young G., Ashley S., Barwell J., Dix F., Nor A.M., Parry C., Birt A., Davies P., George J., Graham A., Jonker L., Kelsall N., Potts C., Wilson T., Crinnion J., Cuenoud L., Aleksic N., Babic S., Ilijevski N., Radak, Sagic D., Tanaskovic S., Colic M., Cvetic V., Davidovic L., Jovanovic D.R., Koncar I., Mutavdzic P., Sladojevic M., Tomic I., Debus E.S., Grzyska U., Otto D., Thomalla G., Barlinn J., Gerber J., Haase K., Hartmann C., Ludwig S., Putz V., Reeps C., Schmidt C., Weiss N., Werth S., Winzer S., Gemper J., Gunther A., Heiling B., Jochmann E., Karvouniari P., Klingner C., Mayer T., Schubert J., Schulze-Hartung F., Zanow J., Bausback Y., Borger F., Botsios S., Branzan D., Braunlich S., Holzer H., Lenzer J., Piorkowski C., Richter N., Schuster J., Scheinert D., Schmidt A., Staab H., Ulrich M., Werner M., Berger H., Biro G., Eckstein H.-H., Kallmayer M., Kreiser K., Zimmermann A., Berekoven B., Frerker K., Gordon V., Torsello G., Arnold S., Dienel C., Storck M., Biermaier B., Gissler H.M., Klotzsch C., Pfeiffer T., Schneider R., Sohl L., Wennrich M., Alonso A., Keese M., Groden C., Coster A., Engelhardt A., Ratusinski C.-M., Berg B., Delle M., Formgren J., Gillgren P., Jarl L., Kall T.B., Konrad P., Nyman N., Skioldebrand C., Steuer J., Takolander R., Malmstedt J., Acosta S., Bjorses K., Brandt K., Dias N., Gottsater A., Holst J., Kristmundsson T., Kuhme T., Kolbel T., Lindblad B., Lindh M., Malina M., Ohrlander T., Resch T., Ronnle V., Sonesson B., Warvsten M., Zdanowski Z., Campbell E., Kjellin P., Lindgren H., Nyberg J., Petersen B., Plate G., Parsson H., Qvarfordt P., Ignatenko P., Karpenko A., Starodubtsev V., Chernyavsky M.A., Golovkova M.S., Komakha B.B., Zherdev N.N., Belyasnik A., Chechulov P., Kandyba D., Stepanishchev I., Csobay-Novak C., Dosa E., Entz L., Nemes B., Szeberin Z., Barzo P., Bodosi M., Fako E., Fulop B., Nemeth T., Pazdernyik S., Skoba K., Voros E., Chatzinikou E., Giannoukas A., Karathanos C., Koutsias S., Kouvelos G., Matsagkas M., Ralli S., Rountas C., Rousas N., Spanos K., Brountzos E., Kakisis J.D., Lazaris A., Moulakakis K.G., Stefanis L., Tsivgoulis G., Vasdekis S., Antonopoulos C.N., Bellenis I., Maras D., Polydorou A., Polydorou V., Tavernarakis A., Ioannou N., Terzoudi M., Lazarides M., Mantatzis M., Vadikolias K., Dzieciuchowicz L., Gabriel M., Krasinski Z., Oszkinis G., Pukacki F., Slowinski M., Stanisic M.-G., Staniszewski R., Tomczak J., Zielinski M., Myrcha P., Rozanski D., Drelichowski S., Iwanowski W., Koncewicz K., Bialek P., Biejat Z., Czepel W., Czlonkowska A., Dowzenko A., Jedrzejewska J., Kobayashi A., Leszczynski J., Malek A., Polanski J., Proczka R., Skorski M., Szostek M., Andziak P., Dratwicki M., Gil R., Nowicki M., Pniewski J., Rzezak J., Seweryniak P., Dabek P., Juszynski M., Madycki G., Pacewski B., Raciborski W., Slowinski P., Staszkiewicz W., Bombic M., Chlouba V., Fiedler J., Hes K., Kostal P., Sova J., Kriz Z., Privara M., Reif M., Staffa R., Vlachovsky R., Vojtisek B., Hrbac T., Kuliha M., Prochazka V., Roubec M., Skoloudik D., Netuka D., Steklacova A., Benes III V., Buchvald P., Endrych L., Sercl M., Campos W., Casella I.B., de Luccia N., Estenssoro A.E.V., Presti C., Puech-Leao P., Neves C.R.B., da Silva E.S., Sitrangulo C.J., Monteiro J.A.T., Tinone G., Bellini Dalio M., Joviliano E.E., Pontes Neto O.M., Serra Ribeiro M., Cras P., Hendriks J.M.H., Hoppenbrouwers M., Lauwers P., Loos C., Yperzeele L., Geenens M., Hemelsoet D., van Herzeele I., Vermassen F., Astarci P., Hammer F., Lacroix V., Peeters A., Verhelst R., Cirelli S., Dormal P., Grimonprez A., Lambrecht B., Lerut P., Thues E., De Koster G., Desiron Q., Maertens de Noordhout A., Malmendier D., Massoz M., Saad G., Bosiers M., Callaert J., Deloose K., Blanco Canibano E., Garcia Fresnillo B., Guerra Requena M., Morata Barrado P.C., Muela Mendez M., Yusta Izquierdo A., Aparici Robles F., Blanes Orti P., Garcia Dominguez L., Martinez Lopez R., Miralles Hernandez M., Tembl Ferrairo J.I., Chamorro A., Macho J., Obach V., Riambau V., San Roman L., Ahlhelm F.J., Blackham K., Engelter S., Eugster T., Gensicke H., Gurke L., Lyrer P., Mariani L., Maurer M., Mujagic E., Muller M., Psychogios M., Stierli P., Stippich C., Traenka C., Wolff T., Wagner B., Wiegert M.M., Clarke S., Diepers M., Grochenig E., Gruber P., Isaak A., Kahles T., Marti R., Nedeltchev K., Remonda L., Tissira N., Valenca Falcao M., de Borst G.J., Lo R.H., Moll F.L., Toorop R., van der Worp B.H., Vonken E.J., Kappelle J.L., Jahrome O., Vos F., Schuiling W., van Overhagen H., Keunen R.W.M., Knippenberg B., Wever J.J., Lardenoije J.W., Reijnen M., Smeets L., van Sterkenburg S., Fraedrich G., Gizewski E., Gruber I., Knoflach M., Kiechl S., Rantner B., Abdulamit T., Bergeron P., Padovani R., Trastour J.-C., Cardon J.-M., Le Gallou-Wittenberg A., Allaire E., Becquemin J.-P., Cochennec-Paliwoda F., Desgranges P., Hosseini H., Kobeiter H., Marzelle J., Almekhlafi M.A., Bal S., Barber P.A., Coutts S.B., Demchuk A.M., Eesa M., Gillies M., Goyal M., Hill M.D., Hudon M.E., Jambula A., Kenney C., Klein G., McClelland M., Mitha A., Menon B.K., Morrish W.F., Peters S., Ryckborst K.J., Samis G., Save S., Smith E.E., Stys P., Subramaniam S., Sutherland G.R., Watson T., Wong J.H., Zimmel L., Flis V., Matela J., Miksic K., Milotic F., Mrdja B., Stirn B., Tetickovic E., Gasparini M., Grad A., Kompara I., Milosevic Z., Palmiste V., Toomsoo T., Aidashova B., Kospanov N., Lyssenko R., Mussagaliev D., Beyar R., Hoffman A., Karram T., Kerner A., Nikolsky E., Nitecki S., Andonova S., Bachvarov C., Petrov V., Cvjetko I., Vidjak V., Haluzan D., Petrunic M., Liu B., Liu C.-W., Bartko D., Beno P., Rusnak F., Zelenak K., Ezura M., Inoue T., Kimura N., Kondo R., Matsumoto Y., Shimizu H., Endo H., Furui E., Bakke S., Krohg-Sorensen K., Nome T., Skjelland M., Tennoe B., Albuquerque e Castro J., Alves G., Bastos Goncalves F., de Aragao Morais J., Garcia A.C., Valentim H., Vasconcelos L., Belcastro F., Cura F., Zaefferer P., Abd-Allah F., Eldessoki M.H., Heshmat Kassem H., Soliman Gharieb H., Colgan M.P., Haider S.N., Harbison J., Madhavan P., Moore D., Shanik G., Kazan V., Nazzal M., Ramsey-Williams V., and Gargiulo M

Subjects
Male, medicine.medical_specialty, Time Factors, Time Factor, medicine.medical_treatment, Carotid Stenosi, MEDLINE, Carotid endarterectomy, Rate ratio, Risk Assessment, Asymptomatic, law.invention, Randomized controlled trial, law, Risk Factors, carotid artery stenting (CAS), carotid endarterectomy (CEA), Stent, medicine, Humans, Carotid Stenosis, Stroke, Endarterectomy, Aged, Endarterectomy, Carotid, business.industry, carotid artery, Risk Factor, Articles, General Medicine, trial, medicine.disease, Settore MED/22 - CHIRURGIA VASCOLARE, Surgery, Stenosis, Treatment Outcome, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Female, Stents, Human medicine, medicine.symptom, business, Human
Abstract

Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.

Published
2021

Catalog

Books, media, physical & digital resources
See catalog results