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1. Detection of Age-Related Hearing Losses (ARHL) via Transient-Evoked Otoacoustic Emissions

Author

Zimatore G, Cavagnaro M, Skarzynski PH, Fetoni AR, and Hatzopoulos S

Subjects
recurrence quantification analysis, early detection, otoacoustic emissions, teoaes, determinism, presbycusis, Geriatrics, RC952-954.6
Abstract

Giovanna Zimatore,1,2 Marta Cavagnaro,3 Piotr H Skarzynski,4– 6 Anna R Fetoni,7 Stavros Hatzopoulos8 1Department of Theoretical and Applied Sciences, eCampus University, Novedrate, CO 22060, Italy; 2Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy; 3Department of Information Engineering, Electronics and Telecommunication, Sapienza University of Rome, Rome, Italy; 4World Hearing Center, Warsaw, Poland; 5Department of Heart Failure and Cardiac Rehabilitation, Medical University of Warsaw, Warsaw, Poland; 6Institute of Sensory Organs, Kajetany, Poland; 7Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy; 8Clinic of Audiology and ENT, University of Ferrara, Ferrara, ItalyCorrespondence: Giovanna ZimatoreDepartment of Theoretical and Applied Sciences, eCampus University Tel +39 338 959 4393Email giovanna.zimatore@uniecampus.itPurpose: The objective of the study was to identify subjects presenting hearing deficits, specifically age-related hearing losses (ARHL), via objective assessment methodologies.Materials and Methods: Initially, 259 subjects (165 men, 94 women) were enrolled in the study. After the application of inclusion criteria, the final number was reduced to 88 subjects (49.8 ± 19.1 ys) subdivided into 64 normal and 83 ARHL cases. The subjects were assessed with traditional audiometry tests and with transiently evoked otoacoustic emissions (TEOAEs). Since each ear has its own acoustic signature, the TEOAE analyses were conducted in terms of ears and not subjects. The TEOAE data were processed by traditional and recurrence quantification analyses, leading to the estimation of the WWR (whole waveform reproducibility) and the new RAD2D (2-dimensional radius) parameters. A plot of WWR vs RAD2D was used to optimize the classification of the cases presenting ARHL.Results: By using a WWR value of 70% as a classifier, the sensitivity of TEOAEs was estimated as 75.9% and the specificity as 89.1%. By using the RAD2D parameter (with a cut-off value of 1.78), a sensitivity value of 80.7% and a specificity value of 71.9% were obtained. When both parameters were used, a sensitivity value of 85.5% and a specificity value of 92.2% were estimated. In the latter classification paradigm, the number of false negatives decreased from 20 to 12 out of 83 ears (14%).Conclusion: In adult hearing screening assessments, the proposed method optimizes the identification of subjects with a hearing impairment correlated to the presence of age-related hearing loss.Keywords: recurrence quantification analysis, early detection, otoacoustic emissions, TEOAEs, determinism, presbycusis

Published
2020

2. Automatic Detection of Aerobic Threshold through Recurrence Quantification Analysis of Heart Rate Time Series

Author

Zimatore, G., Serantoni, Cassandra, Gallotta, M. C., Guidetti, L., Maulucci, Giuseppe, De Spirito, Marco, Serantoni C., Maulucci G. (ORCID:0000-0002-2154-319X), De Spirito M. (ORCID:0000-0003-4260-5107), Zimatore, G., Serantoni, Cassandra, Gallotta, M. C., Guidetti, L., Maulucci, Giuseppe, De Spirito, Marco, Serantoni C., Maulucci G. (ORCID:0000-0002-2154-319X), and De Spirito M. (ORCID:0000-0003-4260-5107)

Abstract

During exercise with increasing intensity, the human body transforms energy with mechanisms dependent upon actual requirements. Three phases of the body’s energy utilization are recognized, characterized by different metabolic processes, and separated by two threshold points, called aerobic (AerT) and anaerobic threshold (AnT). These thresholds occur at determined values of exercise intensity(workload) and can change among individuals. They are considered indicators of exercise capacities and are useful in the personalization of physical activity plans. They are usually detected by ventilatory or metabolic variables and require expensive equipment and invasive measurements. Recently, particular attention has focused on AerT, which is a parameter especially useful in the overweight and obese population to determine the best amount of exercise intensity for weight loss and increasing physical fitness. The aim of study is to propose a new procedure to automatically identify AerT using the analysis of recurrences (RQA) relying only on Heart rate time series, acquired from a cohort of young athletes during a sub-maximal incremental exercise test (Cardiopulmonary Exercise Test, CPET) on a cycle ergometer. We found that the minima of determinism, an RQA feature calculated from the Recurrence Quantification by Epochs (RQE) approach, identify the time points where generic metabolic transitions occur. Among these transitions, a criterion based on the maximum convexity of the determinism minima allows to detect the first metabolic threshold. The ordinary least products regression analysis shows that values of the oxygen consumption VO2, heart rate (HR), and Workload correspondent to the AerT estimated by RQA are strongly correlated with the one estimated by CPET (r > 0.64). Mean percentage differences are <2% for both HR and VO2 and <11% for Workload. The Technical Error for HR at AerT is <8%; intraclass correlation coefficients values are moderate (≥0.66) for all

Published
2023

3. Unsupervised Clustering of Heartbeat Dynamics Allows for Real Time and Personalized Improvement in Cardiovascular Fitness

Author

Serantoni, Cassandra, Zimatore, G., Bianchetti, Giada, Abeltino, Alessio, De Spirito, Marco, Maulucci, Giuseppe, Serantoni C., Bianchetti G., Abeltino A., De Spirito M. (ORCID:0000-0003-4260-5107), Maulucci G. (ORCID:0000-0002-2154-319X), Serantoni, Cassandra, Zimatore, G., Bianchetti, Giada, Abeltino, Alessio, De Spirito, Marco, Maulucci, Giuseppe, Serantoni C., Bianchetti G., Abeltino A., De Spirito M. (ORCID:0000-0003-4260-5107), and Maulucci G. (ORCID:0000-0002-2154-319X)

Abstract

VO2max index has a significant impact on overall health. Its estimation through wearables notifies the user of his level of fitness but cannot provide a detailed analysis of the time intervals in which heartbeat dynamics are changed and/or fatigue is emerging. Here, we developed a multiple modality biosignal processing method to investigate running sessions to characterize in real time heartbeat dynamics in response to external energy demand. We isolated dynamic regimes whose fraction increases with the VO2max and with the emergence of neuromuscular fatigue. This analysis can be extremely valuable by providing personalized feedback about the user's fitness level improvement that can be realized by developing personalized exercise plans aimed to target a contextual increase in the dynamic regime fraction related to VO2max increase, at the expense of the dynamic regime fraction related to the emergence of fatigue. These strategies can ultimately result in the reduction in cardiovascular risk.

Published
2022

4. Detecting Metabolic Thresholds from Nonlinear Analysis of Heart Rate Time Series: A Review

Author

Zimatore, G., Gallotta, M. C., Campanella, Massimo Giuseppe, Skarzynski, P. H., Maulucci, Giuseppe, Serantoni, Cassandra, De Spirito, Marco, Curzi, D., Guidetti, L., Baldari, C., Hatzopoulos, S., Campanella M., Maulucci G. (ORCID:0000-0002-2154-319X), Serantoni C., De Spirito M. (ORCID:0000-0003-4260-5107), Zimatore, G., Gallotta, M. C., Campanella, Massimo Giuseppe, Skarzynski, P. H., Maulucci, Giuseppe, Serantoni, Cassandra, De Spirito, Marco, Curzi, D., Guidetti, L., Baldari, C., Hatzopoulos, S., Campanella M., Maulucci G. (ORCID:0000-0002-2154-319X), Serantoni C., and De Spirito M. (ORCID:0000-0003-4260-5107)

Abstract

Heart rate time series are widely used to characterize physiological states and athletic performance. Among the main indicators of metabolic and physiological states, the detection of metabolic thresholds is an important tool in establishing training protocols in both sport and clinical fields. This paper reviews the most common methods, applied to heart rate (HR) time series, aiming to detect metabolic thresholds. These methodologies have been largely used to assess energy metabolism and to identify the appropriate intensity of physical exercise which can reduce body weight and improve physical fitness. Specifically, we focused on the main nonlinear signal evaluation methods using HR to identify metabolic thresholds with the purpose of identifying a method which can represent a useful tool for the real-time settings of wearable devices in sport activities. While the advantages and disadvantages of each method, and the possible applications, are presented, this review confirms that the nonlinear analysis of HR time series represents a solid, robust and noninvasive approach to assess metabolic thresholds.

Published
2022

5. The Italian multiple sclerosis register

Author

Trojano, M, Bergamaschi, R, Amato, M, Comi, G, Ghezzi, A, Lepore, V, Marrosu, M, Mosconi, P, Patti, F, Ponzio, M, Zaratin, P, Battaglia, M, Acquistapace, D, Aguglia, U, Annunziata, P, Ardito, B, Avolio, C, Balgera, R, Bandini, F, Banfi, P, Barone, P, Bellantonio, P, Bertolotto, A, Bertora, P, Bombardi, R, Bosco Zimatore, G, Bossio, R, Bramanti, P, Brescia Morra, V, Brioschi, A, Bruzzone, M, Buccafusca, M, Busillo, V, Caneve, G, Caniatti, L, Capone, L, Capone, F, Cappellani, A, Cargnelutti, D, Cavaletti, G, Cavalla, P, Celani, M, Centonze, D, Chiveri, L, Clerici, R, Clerico, M, Cocco, E, Comi, C, Coniglio, M, Cordera, S, Corea, F, Cortese, A, Costantino, G, Cottone, S, Crociani, P, D’Andrea, F, Danni, M, De Luca, G, de Pascalis, D, De Robertis, F, De Stefano, N, Di Battista, G, Di Napoli, M, Falcini, M, Fausto, F, Ferrò, M, Florio, C, Fortunato, M, Frittelli, C, Galgani, S, Gallo, P, Gatto, M, Gazzola, P, Geda, C, Giordano, A, Granella, F, Grasso, M, Grimaldi, L, Imperiale, D, Lo Russo, L, Logullo, F, Lugaresi, A, Lus, G, Maccarrone, G, Maimone, D, Malagù, S, Marconi, R, Maritato, P, Massacesi, L, Mazzoni, M, Meucci, G, Mirabella, M, Montepietra, S, Nasuelli, D, Neri, W, Orefice, G, Parodi, S, Pasquali, L, Passarella, B, Peresson, M, Perla, F, Pesci, I, Piantadosi, C, Piras, M, Pizio, N, Pozzilli, C, Protti, A, Pugliatti, M, Quatrale, R, Ragno, M, Rezzonico, M, Ribizzi, G, Riva, M, Ronzoni, M, Rosso, M, Rottoli, M, Rovaris, M, Salemi, G, Salvetti, M, Santangelo, M, Santangelo, G, Santuccio, G, Sarchielli, P, Scarpini, E, Sechi, G, Severi, S, Sinisi, L, Sola, P, Spitaleri, D, Tassinari, T, Tedeschi, G, Tonietti, S, Torri Clerici, V, Totaro, R, Traccis, S, Turla, M, Uccelli, A, Ulivelli, M, Valentino, P, Valeriani, M, Venturi, S, Vianello, M, Zaffaroni, M, Trojano, Maria, Bergamaschi, Roberto, Amato, Maria Pia, Comi, Giancarlo, Ghezzi, Angelo, Lepore, Vito, Marrosu, Maria Giovanna, Mosconi, Paola, Patti, Francesco, Ponzio, Michela, Zaratin, Paola, Battaglia, Mario Alberto, Acquistapace, D., Aguglia, U., Amato, M. P., Annunziata, P., Ardito, B., Avolio, C., Balgera, R., Bandini, F., Banfi, P., Barone, P., Bellantonio, P., Bergamaschi, R., Bertolotto, A., Bertora, P., Bombardi, R., Bosco Zimatore, G., Bossio, R. B., Bramanti, P., Brescia Morra, V., Brioschi, A. M., Bruzzone, M., Buccafusca, M., Busillo, V., Caneve, G., Caniatti, L. M., Capone, L., Capone, F., Cappellani, A., Cargnelutti, D., Cavaletti, G., Cavalla, P., Celani, M. G., Centonze, D., Chiveri, L., Clerici, R., Clerico, M., Cocco, E., Comi, G., Comi, C., Coniglio, M. G., Cordera, S., Corea, F., Cortese, A., Costantino, G., Cottone, S., Crociani, P., D’Andrea, F., Danni, M. C., De Luca, G., de Pascalis, D., De Robertis, F., De Stefano, N., Di Battista, G., Di Napoli, M., Falcini, M., Fausto, F., Ferrò, M. T., Florio, C., Fortunato, M., Frittelli, C., Galgani, S., Gallo, P., Gatto, M., Gazzola, P., Geda, C., Giordano, A., Granella, F., Grasso, M. G., Grimaldi, L. M. E., Imperiale, D., Lo Russo, L., Logullo, F. O., Lugaresi, A., Lus, G., Maccarrone, G., Maimone, D., Malagù, S., Marconi, R., Maritato, P., Massacesi, L., Mazzoni, M., Meucci, G., Mirabella, M., Montepietra, S., Nasuelli, D., Neri, W., Orefice, G., Parodi, S., Pasquali, L., Passarella, B., Patti, F., Peresson, M., Perla, F., Pesci, I., Piantadosi, C., Piras, M. L., Pizio, N. R., Pozzilli, C., Protti, A., Pugliatti, M., Quatrale, R., Ragno, M., Rezzonico, M., Ribizzi, G., Riva, M., Ronzoni, M., Rosso, M. G., Rottoli, M., Rovaris, M., Salemi, G., Salvetti, M., Santangelo, M., Santangelo, G., Santuccio, G., Sarchielli, P., Scarpini, E., Sechi, G. P., Severi, S., Sinisi, L., Sola, P., Spitaleri, D., Tassinari, T., Tedeschi, G., Tonietti, S., Torri Clerici, V., Totaro, R., Traccis, S., Trojano, M., Turla, M., Uccelli, A., Ulivelli, M., Valentino, P., Valeriani, M., Venturi, S., Vianello, M., Zaffaroni, M., Trojano, M, Bergamaschi, R, Amato, M, Comi, G, Ghezzi, A, Lepore, V, Marrosu, M, Mosconi, P, Patti, F, Ponzio, M, Zaratin, P, Battaglia, M, Acquistapace, D, Aguglia, U, Annunziata, P, Ardito, B, Avolio, C, Balgera, R, Bandini, F, Banfi, P, Barone, P, Bellantonio, P, Bertolotto, A, Bertora, P, Bombardi, R, Bosco Zimatore, G, Bossio, R, Bramanti, P, Brescia Morra, V, Brioschi, A, Bruzzone, M, Buccafusca, M, Busillo, V, Caneve, G, Caniatti, L, Capone, L, Capone, F, Cappellani, A, Cargnelutti, D, Cavaletti, G, Cavalla, P, Celani, M, Centonze, D, Chiveri, L, Clerici, R, Clerico, M, Cocco, E, Comi, C, Coniglio, M, Cordera, S, Corea, F, Cortese, A, Costantino, G, Cottone, S, Crociani, P, D’Andrea, F, Danni, M, De Luca, G, de Pascalis, D, De Robertis, F, De Stefano, N, Di Battista, G, Di Napoli, M, Falcini, M, Fausto, F, Ferrò, M, Florio, C, Fortunato, M, Frittelli, C, Galgani, S, Gallo, P, Gatto, M, Gazzola, P, Geda, C, Giordano, A, Granella, F, Grasso, M, Grimaldi, L, Imperiale, D, Lo Russo, L, Logullo, F, Lugaresi, A, Lus, G, Maccarrone, G, Maimone, D, Malagù, S, Marconi, R, Maritato, P, Massacesi, L, Mazzoni, M, Meucci, G, Mirabella, M, Montepietra, S, Nasuelli, D, Neri, W, Orefice, G, Parodi, S, Pasquali, L, Passarella, B, Peresson, M, Perla, F, Pesci, I, Piantadosi, C, Piras, M, Pizio, N, Pozzilli, C, Protti, A, Pugliatti, M, Quatrale, R, Ragno, M, Rezzonico, M, Ribizzi, G, Riva, M, Ronzoni, M, Rosso, M, Rottoli, M, Rovaris, M, Salemi, G, Salvetti, M, Santangelo, M, Santangelo, G, Santuccio, G, Sarchielli, P, Scarpini, E, Sechi, G, Severi, S, Sinisi, L, Sola, P, Spitaleri, D, Tassinari, T, Tedeschi, G, Tonietti, S, Torri Clerici, V, Totaro, R, Traccis, S, Turla, M, Uccelli, A, Ulivelli, M, Valentino, P, Valeriani, M, Venturi, S, Vianello, M, Zaffaroni, M, Trojano, Maria, Bergamaschi, Roberto, Amato, Maria Pia, Comi, Giancarlo, Ghezzi, Angelo, Lepore, Vito, Marrosu, Maria Giovanna, Mosconi, Paola, Patti, Francesco, Ponzio, Michela, Zaratin, Paola, Battaglia, Mario Alberto, Acquistapace, D., Aguglia, U., Amato, M. P., Annunziata, P., Ardito, B., Avolio, C., Balgera, R., Bandini, F., Banfi, P., Barone, P., Bellantonio, P., Bergamaschi, R., Bertolotto, A., Bertora, P., Bombardi, R., Bosco Zimatore, G., Bossio, R. B., Bramanti, P., Brescia Morra, V., Brioschi, A. M., Bruzzone, M., Buccafusca, M., Busillo, V., Caneve, G., Caniatti, L. M., Capone, L., Capone, F., Cappellani, A., Cargnelutti, D., Cavaletti, G., Cavalla, P., Celani, M. G., Centonze, D., Chiveri, L., Clerici, R., Clerico, M., Cocco, E., Comi, G., Comi, C., Coniglio, M. G., Cordera, S., Corea, F., Cortese, A., Costantino, G., Cottone, S., Crociani, P., D’Andrea, F., Danni, M. C., De Luca, G., de Pascalis, D., De Robertis, F., De Stefano, N., Di Battista, G., Di Napoli, M., Falcini, M., Fausto, F., Ferrò, M. T., Florio, C., Fortunato, M., Frittelli, C., Galgani, S., Gallo, P., Gatto, M., Gazzola, P., Geda, C., Giordano, A., Granella, F., Grasso, M. G., Grimaldi, L. M. E., Imperiale, D., Lo Russo, L., Logullo, F. O., Lugaresi, A., Lus, G., Maccarrone, G., Maimone, D., Malagù, S., Marconi, R., Maritato, P., Massacesi, L., Mazzoni, M., Meucci, G., Mirabella, M., Montepietra, S., Nasuelli, D., Neri, W., Orefice, G., Parodi, S., Pasquali, L., Passarella, B., Patti, F., Peresson, M., Perla, F., Pesci, I., Piantadosi, C., Piras, M. L., Pizio, N. R., Pozzilli, C., Protti, A., Pugliatti, M., Quatrale, R., Ragno, M., Rezzonico, M., Ribizzi, G., Riva, M., Ronzoni, M., Rosso, M. G., Rottoli, M., Rovaris, M., Salemi, G., Salvetti, M., Santangelo, M., Santangelo, G., Santuccio, G., Sarchielli, P., Scarpini, E., Sechi, G. P., Severi, S., Sinisi, L., Sola, P., Spitaleri, D., Tassinari, T., Tedeschi, G., Tonietti, S., Torri Clerici, V., Totaro, R., Traccis, S., Trojano, M., Turla, M., Uccelli, A., Ulivelli, M., Valentino, P., Valeriani, M., Venturi, S., Vianello, M., and Zaffaroni, M.

Abstract

The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups.

Published
2019

9. Recurrence quantification analysis of heart rate variability during continuous incremental exercise test in obese subjects

Author

Zimatore, G., Gallotta, M. C., Innocenti, L., Bonavolonta, V., Ciasca, G., De Spirito, M., Guidetti, L., Baldari, C., Ciasca G. (ORCID:0000-0002-3694-8229), De Spirito M. (ORCID:0000-0003-4260-5107), Zimatore, G., Gallotta, M. C., Innocenti, L., Bonavolonta, V., Ciasca, G., De Spirito, M., Guidetti, L., Baldari, C., Ciasca G. (ORCID:0000-0002-3694-8229), and De Spirito M. (ORCID:0000-0003-4260-5107)

Abstract

The present paper concerns a new description of changing in metabolism during incremental exercises test that permit an individually tailored program of exercises for obese subjects. We analyzed heart rate variability from RR interval time series (tachogram) with an alternative approach, the recurrence quantification analysis, that allows a description of a time series in terms of its dynamic structure and is able to identify the phase transitions. A transition in cardiac signal dynamics was detected and it perfectly reflects the aerobic threshold, as identified by gas exchange during an incremental exercise test, revealing the coupling from the respiratory system toward the heart. Moreover, our analysis shows that, in the recurrence plot of RR interval, it is possible to identify a specific pattern that allows to identify phase transitions between different dynamic regimes. The perfect match of the occurrence of the phase transitions with changes observed in the VO2 consumption, the gold standard approach to estimate thresholds, strongly supports the possibility of using our analysis of RR interval to detect metabolic threshold. In conclusion, we propose a novel nonlinear data analysis method that allows for an easy and personalized detection of thresholds both from professional and even from low-cost wearable devices, without the need of expensive gas analyzers.

Published
2020

16. A Multicentric Prospective Incidence Study of Guillain-Barré Syndrome in Italy. The ITANG Study

Author

Benedetti, M, Pugliatti, M, Dalessandro, R, BEGHI, ETTORE, Chiò, A, Logroscino, G, Filippini, G, Galeotti, F, Massari, M, Santuccio, C, Raschetti, R, Abruzzi, L, Agazzi, E, Agostoni, E, Ambrogio, L, Amidei, S, Arbasino, C, Argentiero, V, Arnaboldi, M, Baldini, D, Barki, R, Bassi, P, Basso, F, Belcastro, V, Bellotti, M, Bersano, E, Besana, R, Bettoni, L, Bezzi, G, Bianconi, C, Bondavalli, M, Bonometti, A, Borghi, AM, Borsato, C, Bortolotto, S, Bottacchi, EF, Bresolin, N, Bruno, S, Burlina, A, Cafasso, G, Callegarini, C, Calvo, A, Candeloro, E, Casano, A, Cattaneo, SI, Cavallo, R, Cheldi, A, Ciardo, G, Cirignotta, F, Clerici, AM, Clerici, R, Comi, G, Conti, R, Coppo, F, Covelli, V, Crespi, V, Currò Dossi, M, Curtò, NA, D'Adda, E, Dallocchio, C, D'Anna, S, De Massis, P, De Toni Franceschini, L, Di Vito, N, Didonè, G, Dileone, M, Donati, E, Dotta, M, Fazio, R, Federico, F, FERRARESE, CARLO, Ferrazzini, F, Ferrero, B, Filosto, M, Frasson, E, Fusina, S, Galbussera, A, Gastaldo, E, Geda, C, Ghiglione, P, Giometto, B, Gionco, M, Giorgetti, A, Giussani, G, Gobbin, F, Grampa, G, Granieri, E, Greco, G, Guidetti, D, Guidi, C, Guidotti, M, Gusmaroli, G, Imperiale, D, Internò, S, Jann, S, La Spina, I, Leo, A, Leone, M, Leoni, S, Leotta, D, Lerario, R, Liotta, G, Livrea, P, Luda di Cortemiglio, E, Maggio, B, Magni, E, Magnoni, A, Maistrelli, J, Manca, D, Mandrioli, J, Manera, U, Marcello, N, Marchi, P, Marchini, C, Marconi, S, Mattioli, M, Mauro, A, Mazzaglia, G, Medici, D, Meineri, P, Meola, G, Micaglio, G, Michelucci, R, Michieli, G, Micieli, G, Minardi, C, Moglia, C, Monaco, S, Montanari, E, Moretto, G, Munerati, V, Mura, G, Mussutto, V, Nascimbene, C, Neri, W, Nichelli, P, Nobile Orazio, E, Oddenino, E, Onorato, S, Padovani, A, Palermo, M, Papurello, DM, Passarella, B, Pavesi, G, Penza, MT, Perini, M, Perini, F, Perla, F, Perlotto, N, Perrone, P, Pignatta, P, Pisano, F, Poglio, F, Polo, A, Poloni, M, Porazzi, D, Pradotto, L, Previdi, P, Quatrale, R, Rasi, F, Ravasio, A, Ravetti, C, Repaci, M, Riccardi, T, Riguzzi, P, Rinaldi, R, Riva, M, Romeo, V, Romorini, A, Rosso, T, Rotondo, G, Sacquegna, T, Sanson, F, Santamato, V, Santoro, D, Sartori, V, Sasanelli, F, Savio, K, Serena, M, Silani, V, Silvestri, L, Simioni, V, Squintani, GM, Suardelli, M, Tartagla, L, Terenghi, F, Terlizzi, E, Terzano, M, Tesser, F, Testa, L, Ticca, A, Ticozzi, N, Tiriticco, M, Tola, MR, Tonietti, S, Trianni, G, Trojano, M, Trotta, F, Turatti, M, Ursino, E, Vanotti, A, Vercellino, M, Villani, A, Vitelli, E, Zambito Marsala, S, Zanette, G, Zarcone, D, Zimatore, G, Zoccolella, S., Benedetti, Md, Pugliatti, M, D'Alessandro, R, Beghi, E, Chiò, A, Logroscino, G, Filippini, G, Galeotti, F, Massari, M, Santuccio, C, Comi, Giancarlo, Raschetti, R, ITANG Study, Group, Giometto, B, Benedetti, M, Dalessandro, R, Abruzzi, L, Agazzi, E, Agostoni, E, Ambrogio, L, Amidei, S, Arbasino, C, Argentiero, V, Arnaboldi, M, Baldini, D, Barki, R, Bassi, P, Basso, F, Belcastro, V, Bellotti, M, Bersano, E, Besana, R, Bettoni, L, Bezzi, G, Bianconi, C, Bondavalli, M, Bonometti, A, Borghi, A, Borsato, C, Bortolotto, S, Bottacchi, E, Bresolin, N, Bruno, S, Burlina, A, Cafasso, G, Callegarini, C, Calvo, A, Candeloro, E, Casano, A, Cattaneo, S, Cavallo, R, Cheldi, A, Ciardo, G, Cirignotta, F, Clerici, A, Clerici, R, Comi, G, Conti, R, Coppo, F, Covelli, V, Crespi, V, Currò Dossi, M, Curtò, N, D'Adda, E, Dallocchio, C, D'Anna, S, De Massis, P, De Toni Franceschini, L, Di Vito, N, Didonè, G, Dileone, M, Donati, E, Dotta, M, Fazio, R, Federico, F, Ferrarese, C, Ferrazzini, F, Ferrero, B, Filosto, M, Frasson, E, Fusina, S, Galbussera, A, Gastaldo, E, Geda, C, Ghiglione, P, Gionco, M, Giorgetti, A, Giussani, G, Gobbin, F, Grampa, G, Granieri, E, Greco, G, Guidetti, D, Guidi, C, Guidotti, M, Gusmaroli, G, Imperiale, D, Internò, S, Jann, S, La Spina, I, Leo, A, Leone, M, Leoni, S, Leotta, D, Lerario, R, Liotta, G, Livrea, P, Luda di Cortemiglio, E, Maggio, B, Magni, E, Magnoni, A, Maistrelli, J, Manca, D, Mandrioli, J, Manera, U, Marcello, N, Marchi, P, Marchini, C, Marconi, S, Mattioli, M, Mauro, A, Mazzaglia, G, Medici, D, Meineri, P, Meola, G, Micaglio, G, Michelucci, R, Michieli, G, Micieli, G, Minardi, C, Moglia, C, Monaco, S, Montanari, E, Moretto, G, Munerati, V, Mura, G, Mussutto, V, Nascimbene, C, Neri, W, Nichelli, P, Nobile Orazio, E, Oddenino, E, Onorato, S, Padovani, A, Palermo, M, Papurello, D, Passarella, B, Pavesi, G, Penza, M, Perini, M, Perini, F, Perla, F, Perlotto, N, Perrone, P, Pignatta, P, Pisano, F, Poglio, F, Polo, A, Poloni, M, Porazzi, D, Pradotto, L, Previdi, P, Quatrale, R, Rasi, F, Ravasio, A, Ravetti, C, Repaci, M, Riccardi, T, Riguzzi, P, Rinaldi, R, Riva, M, Romeo, V, Romorini, A, Rosso, T, Rotondo, G, Sacquegna, T, Sanson, F, Santamato, V, Santoro, D, Sartori, V, Sasanelli, F, Savio, K, Serena, M, Silani, V, Silvestri, L, Simioni, V, Squintani, G, Suardelli, M, Tartagla, L, Terenghi, F, Terlizzi, E, Terzano, M, Tesser, F, Testa, L, Ticca, A, Ticozzi, N, Tiriticco, M, Tola, M, Tonietti, S, Trianni, G, Trojano, M, Trotta, F, Turatti, M, Ursino, E, Vanotti, A, Vercellino, M, Villani, A, Vitelli, E, Zambito Marsala, S, Zanette, G, Zarcone, D, Zimatore, G, and Zoccolella, S

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Epidemiology, Population, Guillain-Barre Syndrome, Rate ratio, NO, Young Adult, Axonal and demyelinating GBS, Guillain-Barré syndrome, Incidence, Prospective study, Trend, Neurology (clinical), Aged, Aged, 80 and over, Female, Humans, Italy, Middle Aged, 80 and over, medicine, Young adult, education, Prospective cohort study, education.field_of_study, Guillain-Barre syndrome, business.industry, Medicine (all), Incidence (epidemiology), medicine.disease, Vaccination, Settore MED/26 - NEUROLOGIA, business, Human
Abstract

Background: To assess Guillain-Barré syndrome (GBS) incidence we relied on the Italian Network for the study of GBS (ITANG) established in 2010 in 7 Italian regions to analyse the association between influenza vaccination and GBS. Methods: All individuals aged ≥18 years, presenting with clinical manifestations that suggested GBS according to the universally accepted Asbury's diagnostic criteria (1990) were prospectively notified to a centralised database by ITANG neurologists over the period October 1, 2010-September 30, 2011. Through a telephone survey, 9 trained interviewers followed up the cases to diagnosis and then for 1 year since hospital discharge. Validation of case reporting was performed with the support of administrative data in 5 regions. Results: We found 365 cases fulfilling the definition for GBS or one of its variants over 19,846,068 population ≥18 years of age, yielding an annual incidence rate of 1.84 per 100,000 (95% CI 1.65-2.03), 2.30 (95% CI 1.99-2.60) in men and 1.41 (95% CI 1.18-1.64) in women. A highly significant peak of incidence was observed in February 2011 as compared to reference month (September 2011, rate ratio 3.3:1, p < 0.01). Conclusions: In Italy, GBS incidence was among the highest reported in Europe and higher than previously observed in Italian studies.

Published
2015

18. Experience of an information aid for newly diagnosed multiple sclerosis patients: A qualitative study on the SIMS-Trial

Author

Borreani, Claudia, Giordano, Andrea, Falautano, Monica, Lugaresi, Alessandra, Martinelli, Vittorio, Granella, Franco, Tortorella, Carla, Plasmati, Imma, Radaelli, Marta, Farina, Deborah, Dalla Bella, Eleonora, Bianchi, Elisabetta, Acquarone, Nicola, Miccinesi, Guido, Solari, Alessandra, D'Alessandro, R., Pucci, E., Uccelli, M. M., Trojano, M., Heesen, C., Mancardi, G. L., Milanese, C., Calabrese, D., Ferrari, G., Mattarozzi, K., Confalonieri, P., Antozzi, C., Maggi, L., Mantegazza, R., Martinelli, V., Colombo, B., Esposito, F., Moiola, L., Rodegher, M., Immovilli, P., De Luca, Giovanna, Di Tommaso, V., Di Ioia, M., Travaglini, D., Pietrolongo, E., Zimatore, G., Borreani, Claudia, Giordano, Andrea, Falautano, Monica, Lugaresi, Alessandra, Martinelli, Vittorio, Granella, Franco, Tortorella, Carla, Plasmati, Imma, Radaelli, Marta, Farina, Deborah, Dalla Bella, Eleonora, Bianchi, Elisabetta, Acquarone, Nicola, Miccinesi, Guido, Solari, Alessandra, D'Alessandro, R., Pucci, E., Uccelli, M. M., Trojano, M., Heesen, C., Mancardi, G. L., Milanese, C., Calabrese, D., Ferrari, G., Mattarozzi, K., Confalonieri, P., Antozzi, C., Maggi, L., Mantegazza, R., Martinelli, V., Colombo, B., Esposito, F., Moiola, L., Rodegher, M., Immovilli, P., De Luca, Giovanna, Di Tommaso, V., Di Ioia, M., Travaglini, D., Pietrolongo, E., and Zimatore, G.

Subjects
Adult, Male, Clinical Trials as Topic, Patient, Time Factor, Public Health, Environmental and Occupational Health, Middle Aged, Diagnosis communication, Complex intervention, Patient Education as Topic, Physician, Multiple Sclerosi, Female, Qualitative study, Shared decision making, Qualitative Research, Human
Abstract

Background The SIMS-Trial (ISRCTN81072971) proved the effectiveness, in terms of patient's knowledge and care satisfaction, of an add-on information aid (personal interview with a physician using a navigable CD and take-home booklet) in 120 newly diagnosed patients with multiple sclerosis (MS) from five Italian centres. Objective To scrutinize the experience of SIMS-Trial participants in order to gain better understanding of the effectiveness of the information aid and its components. Design We performed (i) nine individual semi-structured interviews with a purposeful sample of SIMS-Trial patients who received the information aid, (ii) focus group meeting (FGM) with the physicians who conducted the personal interview, and (iii) FGM with patients' caring neurologists. Results Patients' experience with the information aid was positive as it enhanced their understanding of their disease, being viewed as a guided tour of their medical condition. The physicians who conducted the personal interviews were also positive in their overall evaluation but noted an initial difficulty in using the CD. The caring neurologists had limited direct experience of the aid, and their views were confined to utility of the information aid in general. All participants considered the combination of personal interview, CD navigation and take-home booklet essential, but urged a more flexible scheduling of the personal interview. It also emerged that some content required revision and that the aid was unsuitable for patients with primary progressive MS. Conclusions The results of the study further support the value of the aid and also provide important indications for improving it and refining indications for use. © 2011 John Wiley & Sons Ltd.

Published
2014

19. Predictors of definite Multiple Sclerosis in patients with pediatric onset first demyelinating clinical attack

Author

SALEMI, Giuseppe, Iaffaldano P, Lucisano G, Ghezzi A, Comi V, Brescia Morra V, Patti F, Lugaresi A, Pozzilli C, Amato M, Millefiorini E, Lus G, Zimatore G, Maimone D, Coniglio G, Bergamaschi R, Marrosu M, Tedeschi G, Ardito D, Giuliani G, Avolio C, Montanari E, Simone M, Margari L, Lepore V, Trojano M., Salemi, G, and Iaffaldano P, Lucisano G, Ghezzi A, Comi V, Brescia Morra V, Patti F, Lugaresi A, Pozzilli C, Amato M, Millefiorini E, Lus G, Zimatore G, Maimone D, Coniglio G, Bergamaschi R, Marrosu M, Tedeschi G, Ardito D, Giuliani G, Avolio C, Montanari E, Simone M, Margari L, Lepore V, Trojano M

Subjects
Multiple Sclerosis, pediatric onset, Settore MED/26 - Neurologia
Published
2014

20. Safety of the first dose of fingolimod for multiple sclerosis: results of an open-label clinical trial

Author

Laroni A., Brogi D., Morra V. B., Guidi L., Pozzilli C., Comi G., Lugaresi A., Turrini R., Raimondi D., Uccelli A., Mancardi G. L., Amato M. P., Appendino L., Ardito B., Avolio C., Bandini F., Batocchi A. P., Bellantonio P., Benedetti M. D., Bergamaschi R., Bortolon F., Bosco A., Buccafusca M., Cargnelutti D., Cavalla P., Cavallo R., Centonze D., Coniglio M. G., Costantino G., Cottone S., Danni M. C., De Robertis F., Deotto L., Dotta M., Di Battista G., Filippi M. M., Florio C., Francia A., Galgani S., Gallo P., Ghezzi A., Giometto B., Giuliani G., Grimaldi L. M. E., Guidotti M., Iudice A., Lenzi G. L., Lorusso L., Lus G., Maimone D., Malentacchi G. M., Mantegazza R. E., Massacesi L., Melato M., Millefiorini E., Montanari E., Patti F., Perrone P. S. M., Protti A., Provera P., Quattrone A., Rasi F., Rosati G., Rovaris M., Sacca F., Salemi G., Sarchielli P., Scarpini E. A., Schoenhuber R., Serrati C., Sinisi L., Sola P., Spitaleri D. L. A., Tedeschi G., Tezzon F., Tinebra Asti M. C., Tola M. R., Totaro R., Trojano M., Ulivelli M., Vecchio M. M., Zimatore G. B., Alice Laroni, Davide Brogi, Vincenzo Brescia Morra, Leonello Guidi, Carlo Pozzilli, Giancarlo Comi, Alessandra Lugaresi, Renato Turrini, Debora Raimondi, Antonio Uccelli, Giovanni Mancardi, EAP Investigators, Laroni, A, Brogi, D, BRESCIA MORRA, Vincenzo, Guidi, L, Pozzilli, C, Comi, G, Lugaresi, A, Turrini, R, Raimondi, D, Uccelli, A, Macardi, G., Laroni A, Brogi D, Morra VB, Guidi L, Pozzilli C, Comi G, Lugaresi A, Turrini R, Raimondi D, Uccelli A, Mancardi GL, Amato MP, Appendino L, Ardito B, Avolio C, Bandini F, Batocchi AP, Bellantonio P, Benedetti MD, Bergamaschi R, Bortolon F, Bosco A, Buccafusca M, Cargnelutti D, Cavalla P, Cavallo R, Centonze D, Coniglio MG, Costantino G, Cottone S, Danni MC, De Robertis F, Deotto L, Dotta M, Di Battista G, Filippi MM, Florio C, Francia A, Galgani S, Gallo P, Ghezzi A, Giometto B, Giuliani G Grimaldi LME, Guidotti M, Iudice A, Lenzi GL, Lorusso L, Lus G, Maimone D, Malentacchi GM, Mantegazza RE, Massacesi L, Melato M, Millefiorini E, Montanari E, Patti F, Perrone PSM, Protti A, Provera P, Quattrone A, Rasi F, Rosati G, Rovaris M, Saccà F, Salemi G, Sarchielli P, Scarpini EA, Schoenhuber R, Serrati C, Sinisi L, Sola P, Spitaleri DLA, Tedeschi G, Tezzon F, Tinebra Asti MC, Tola MR, Totaro R, Trojano M, Ulivelli M, Vecchio MM, Zimatore GB, Laroni, A., Brogi, D., Morra, V. B., Guidi, L., Pozzilli, C., Comi, G., Lugaresi, A., Turrini, R., Raimondi, D., Uccelli, A., Mancardi, G. L., Amato, M. P., Appendino, L., Ardito, B., Avolio, C., Bandini, F., Batocchi, A. P., Bellantonio, P., Benedetti, M. D., Bergamaschi, R., Bortolon, F., Bosco, A., Buccafusca, M., Cargnelutti, D., Cavalla, P., Cavallo, R., Centonze, D., Coniglio, M. G., Costantino, G., Cottone, S., Danni, M. C., De Robertis, F., Deotto, L., Dotta, M., Di Battista, G., Filippi, M. M., Florio, C., Francia, A., Galgani, S., Gallo, P., Ghezzi, A., Giometto, B., Giuliani, G., Grimaldi, L. M. E., Guidotti, M., Iudice, A., Lenzi, G. L., Lorusso, L., Lus, G., Maimone, D., Malentacchi, G. M., Mantegazza, R. E., Massacesi, L., Melato, M., Millefiorini, E., Montanari, E., Patti, F., Perrone, P. S. M., Protti, A., Provera, P., Quattrone, A., Rasi, F., Rosati, G., Rovaris, M., Sacca, F., Salemi, G., Sarchielli, P., Scarpini, E. A., Schoenhuber, R., Serrati, C., Sinisi, L., Sola, P., Spitaleri, D. L. A., Tedeschi, G., Tezzon, F., Tinebra Asti, M. C., Tola, M. R., Totaro, R., Trojano, M., Ulivelli, M., Vecchio, M. M., Zimatore, G. B., Mancardi, Gl, Brescia Morra, V, on behalf of the EAP, Investigator, and Giometto, B

Subjects
Oncology, Male, Neurology, fingolimod, multiple sclerosis, treatment, first dose, safety, administration /&/ dosage/adverse effects/analogs /&/ derivatives/therapeutic use, Immunosuppressive Agent, Sphingosine, Multiple Sclerosi, Atrioventricular Block, administration /&/ dosage/adverse effects/therapeutic use, General Medicine, Middle Aged, Tolerability, Propylene Glycol, Fingolimod, drug therapy, Anesthesia, Cohort, Adolescent, Adult, Atrioventricular Block, chemically induced/epidemiology, Drug Therapy, Combination, Female, Humans, Immunosuppressive Agents, administration /&/ dosage/adverse effects/therapeutic use, Male, Middle Aged, Multiple Sclerosis, drug therapy, Propylene Glycols, administration /&/ dosage/adverse effects/therapeutic use, Sphingosine, administration /&/ dosage/adverse effects/analogs /&/ derivatives/therapeutic use, Young Adult, Combination, Drug Therapy, Combination, Settore MED/26 - Neurologia, Female, Atrioventricular block, Bradycardia, Multiple sclerosis, Safety, Adolescent, Adult, Fingolimod Hydrochloride, Humans, Immunosuppressive Agents, Multiple Sclerosis, Propylene Glycols, Young Adult, Neurology (clinical), Atrioventricular block, Bradicardia, Multiple sclerosis, Fingolimod, Safety Tolerability, Research Article, Human, medicine.drug, medicine.medical_specialty, Clinical Neurology, Internal medicine, medicine, Neurochemistry, business.industry, medicine.disease, Clinical trial, Atrioventricular block, Bradycardia, Multiple sclerosis, Fingolimod, Safety, Tolerability, chemically induced/epidemiology, business
Abstract

BACKGROUND: In patients with relapsing-remitting MS (RRMS) fingolimod prevents disease relapses and delays disability progression. First dose administration of fingolimod is associated with a transient, dose-dependent decrease in heart rate (HR) in the 6 hours after drug intake.The aim of the study is to to assess safety and tolerability of the first dose of fingolimod in a cohort of Italian patients with RRMS without alternative therapeutic options. METHODS: Open-label, single arm, multicentre study. After the first dose of fingolimod, patients were observed for 6 hours and had their vital signs monitored hourly. Extended on-site monitoring was provided when required. RESULTS: Of the 906 patients enrolled in the study, most (95.2%) did not experience any adverse event (AE) following fingolimod administration. Cardiovascular AEs occurred in 18 patients and included bradycardia (1.3%), first-and second-degree atrioventricular block (0.1% and 0.2%), palpitations (0.1%), sinus arrhythmia (0.1%) and ventricular premature beats (0.1%). All events were self-limiting and did not require any intervention. Extended monitoring was required in 34 patients. CONCLUSIONS: These results, in a population who better resembled real-world clinical practice in terms of concomitant diseases and medications, are consistent with previous clinical trials and confirmed that the first dose administration of fingolimod is generally safe and well tolerated. TRIAL REGISTRATION: EudraCT 2011-000770-60.

Published
2014

21. The Multiple Sclerosis Knowledge Questionnaire: a self-administered instrument for recently diagnosed patients

Author

Giordano, A, Uccelli, Mm, Pucci, E, Martinelli, V, Borreani, C, Lugaresi, A, Trojano, M, Granella, F, Confalonieri, P, Radice, D, Solari, A, D'Alessandro, R, Heesen, C, Mancardi, Gl, Milanese, C, Galimberti, S, Calabrese, D, Ferrari, G, Mattarozzi, K, Antozzi, C, Lauria, G, La Mantia, L, Pedotti, R, Mantegazza, R, Maggi, L, Colombo, B, Esposito, F, Moiola, L, Rodegher, M, Radaelli, M, Immovilli, P, Dalla Bella, E, De Luca, G, Mattoscio, M, Di Ioia, M, Pace, M, Travaglini, D, Maruotti, V, Farina, D, Zimatore, G, Plasmati, I, Tortorella, C., Giordano A., Uccelli M.M., Pucci E., Martinelli V., Borreani C., Lugaresi A., Trojano M., Granella F., Confalonieri P., Radice D., Solari A., D'Alessandro R., Heesen C., Mancardi G.L., Milanese C., Galimberti S., Calabrese D., Ferrari G., Mattarozzi K., Antozzi C., Lauria G., La Mantia L., Pedotti R., Mantegazza R., Maggi L., Colombo B., Esposito F., Moiola L., Rodegher M., Radaelli M., Immovilli P., Dalla Bella E., De Luca G., Mattoscio M., Di Ioia M., Pace M., Travaglini D., Maruotti V., Farina D., Zimatore G., Plasmati I., Tortorella C., (SIMS-Trial group)., Giordano, A., Uccelli, M. M., Pucci, E., Martinelli, V., Borreani, C., Lugaresi, A., Trojano, M., Granella, F., Confalonieri, P., Radice, D., Solari, A., D'Alessandro, R., Heesen, C., Mancardi, G. L., Milanese, C., Galimberti, S., Calabrese, D., Ferrari, G., Mattarozzi, K., Antozzi, C., Lauria, G., La Mantia, L., Pedotti, R., Mantegazza, R., Maggi, L., Colombo, B., Esposito, F., Moiola, L., Rodegher, M., Radaelli, M., Immovilli, P., Dalla Bella, E., De Luca, G., Mattoscio, M., Di Ioia, M., Pace, M., Travaglini, D., Maruotti, V., Farina, D., Zimatore, G., Plasmati, I., and Tortorella, C.

Subjects
Questionnaires, Male, law.invention, Disability Evaluation, Randomized controlled trial, Informed consent, law, Surveys and Questionnaires, Multiple Sclerosi, Content validity, Surveys and Questionnaire, Medicine, Young adult, Patient-reported outcome, Informed Consent, Psychiatric Status Rating Scale, Middle Aged, Newly diagnosed, Test (assessment), Knowledge, Neurology, Italy, drug therapy/psychology, Female, Human, Adult, Employment, medicine.medical_specialty, Multiple Sclerosis, Logistic Model, Adolescent, multiple sclerosis, questionnaire, MEDLINE, Reproducibility of Result, Education, Young Adult, Patient Education as Topic, Adolescent, Adult, Disability Evaluation, Education, Employment, Female, Humans, Informed Consent, Italy, Logistic Models, Male, Middle Aged, Multiple Sclerosis, drug therapy/psychology, Patient Education as Topic, Psychiatric Status Rating Scales, Questionnaires, Reproducibility of Results, Young Adult, Humans, Psychiatric Status Rating Scales, Questionnaire, business.industry, Construct validity, Reproducibility of Results, Surgery, Clinical trial, Logistic Models, Measurement development, Physical therapy, Neurology (clinical), business
Abstract

There are few studies on patient knowledge in multiple sclerosis (MS), and only two published questionnaires. The objective of this article was to develop and validate the MS Knowledge Questionnaire (MSKQ), a self-assessed instrument for newly diagnosed MS patients. Thirty multiple-choice statements, conceived to test MS knowledge, were produced by a multidisciplinary panel and pre-tested on three MS patients, resulting in an intermediate 26-item version. This was tested on 54 MS patients for internal consistency, content and construct validity (validation sample I). The final (25-item) MSKQ was a primary outcome measure in the SIMS-Trial on an information aid to newly diagnosed MS patients. Postal responses of SIMS-Trial participants to the MSKQ a month after intervention (validation sample II) were analysed. Median MSKQ scores in validation samples I and II were, respectively, 18 (range 9—23) and 17 (range 3—24). Acceptability, internal consistency (Kuder—Richardson-20 formula 0.76) and content validity were good. Educational attainment and receiving the information aid were the main independent predictors of MS knowledge. Other predictors were female sex (positive association) and disease duration (negative association). In conclusion, the MSKQ has good clinimetric properties and is sensitive to an educational intervention. We propose the MSKQ as a brief instrument for clinical practice and research.

Published
2009

23. Experience of an information aid for newly diagnosed multiple sclerosis patients: a qualitative study on the SIMS-Trial

Author

Borreani, C, Giordano, A, Falautano, M, Lugaresi, A, Martinelli, V, Granella, F, Tortorella, C, Plasmati, I, Radaelli, M, Dalla Bella, E, Bianchi, E, Acquarone, N, Miccinesi, G, Solari, A, D' Alessandro, R, Pucci, E, Uccelli, Mm, Trojano, M, Heesen, C, Mancardi, Gl, Milanese, C, Calabrese, D, Ferrari, G, Mattarozzi, K, Confalonieri, P, Antozzi, C, Maggi, L, Mantegazza, R, Colombo, B, Esposito, F, Moiola, L, Rodegher, M, Immovilli, P, Farina, D, De Luca, G, Di Tommaso, V, Di Ioia, M, Travaglini, D, Pietrolongo, E, and Zimatore, G.

Subjects
Adult, Male, Clinical Trials as Topic, Multiple Sclerosis, Time Factors, Patient Education as Topic, Patients, Physicians, Humans, Female, Middle Aged, Original Research Papers, Qualitative Research
Abstract

The SIMS-Trial (ISRCTN81072971) proved the effectiveness, in terms of patient's knowledge and care satisfaction, of an add-on information aid (personal interview with a physician using a navigable CD and take-home booklet) in 120 newly diagnosed patients with multiple sclerosis (MS) from five Italian centres.To scrutinize the experience of SIMS-Trial participants in order to gain better understanding of the effectiveness of the information aid and its components.We performed (i) nine individual semi-structured interviews with a purposeful sample of SIMS-Trial patients who received the information aid, (ii) focus group meeting (FGM) with the physicians who conducted the personal interview, and (iii) FGM with patients' caring neurologists.Patients' experience with the information aid was positive as it enhanced their understanding of their disease, being viewed as a guided tour of their medical condition. The physicians who conducted the personal interviews were also positive in their overall evaluation but noted an initial difficulty in using the CD. The caring neurologists had limited direct experience of the aid, and their views were confined to utility of the information aid in general. All participants considered the combination of personal interview, CD navigation and take-home booklet essential, but urged a more flexible scheduling of the personal interview. It also emerged that some content required revision and that the aid was unsuitable for patients with primary progressive MS.The results of the study further support the value of the aid and also provide important indications for improving it and refining indications for use.

Published
2014

24. A Multicentric Prospective Incidence Study of Guillain-Barre Syndrome in Italy. the ITANG Study

Author

Benedetti, M. D., Pugliatti, M., Dalessandro, R., Beghi, E., Chio, A., Logroscino, G., Filippini, G., Galeotti, F., Massari, M., Santuccio, C., Raschetti R., Abruzzi L, Agazzi, E, Agostoni, E, Ambrogio, L, Amidei, S, Arbasino, C, Argentiero, V, Arnaboldi, M, Baldini, D, Barki, R, Bassi, P, Basso, F, Belcastro, V, Bellotti, M, Bersano, E, Besana, R, Bettoni, L, Bezzi, G, Bianconi, C, Bondavalli, M, Bonometti, A, Borghi, Am, Borsato, C, Bortolotto, S, Bottacchi, Ef, Bresolin, N, Bruno, S, Burlina, A, Cafasso, G, Callegarini, C, Calvo, A, Candeloro, E, Casano, A, Cattaneo, Si, Cavallo, R, Cheldi, A, Ciardo, G, Cirignotta, F, Clerici, Am, Clerici, R, Comi, G, Conti, R, Coppo, F, Covelli, V, Crespi, V, Currò Dossi, M, Curtò, Na, D'Adda, E, Dallocchio, C, D'Anna, S, De Massis, P, De Toni Franceschini, L, Di Vito, N, Didonè, G, Dileone, M, Donati, E, Dotta, M, Fazio, R, Federico, F, Ferrarese, C, Ferrazzini, F, Ferrero, B, Filosto, M, Frasson, E, Fusina, S, Galbussera, A, Gastaldo, E, Geda, C, Ghiglione, P, Giometto, B, Gionco, M, Giorgetti, A, Giussani, G, Gobbin, F, Grampa, G, Granieri, E, Greco, G, Guidetti, D, Guidi, C, Guidotti, M, Gusmaroli, G, Imperiale, D, Internò, S, Jann, S, La Spina, I, Leo, A, Leone, M, Leoni, S, Leotta, D, Lerario, R, Liotta, G, Livrea, P, Luda di Cortemiglio, E, Maggio, B, Magni, Eugenio, Magnoni, A, Maistrelli, J, Manca, D, Mandrioli, J, Manera, U, Marcello, N, Marchi, P, Marchini, C, Marconi, S, Mattioli, M, Mauro, A, Mazzaglia, G, Medici, D, Meineri, P, Meola, G, Micaglio, G, Michelucci, R, Michieli, G, Micieli, G, Minardi, C, Moglia, C, Monaco, S, Montanari, E, Moretto, G, Munerati, V, Mura, G, Mussutto, V, Nascimbene, C, Neri, W, Nichelli, P, Nobile-Orazio, E, Oddenino, E, Onorato, S, Padovani, A, Palermo, M, Papurello, Dm, Passarella, B, Pavesi, G, Penza, Mt, Perini, M, Perini, F, Perla, F, Perlotto, N, Perrone, P, Pignatta, P, Pisano, F, Poglio, F, Polo, A, Poloni, M, Porazzi, D, Pradotto, L, Previdi, P, Quatrale, R, Rasi, F, Ravasio, A, Ravetti, C, Repaci, M, Riccardi, T, Riguzzi, P, Rinaldi, R, Riva, M, Romeo, V, Romorini, A, Rosso, T, Rotondo, G, Sacquegna, T, Sanson, F, Santamato, V, Santoro, D, Sartori, V, Sasanelli, F, Savio, K, Serena, M, Silani, V, Silvestri, L, Simioni, V, Squintani, Gm, Suardelli, M, Tartagla, L, Terenghi, F, Terlizzi, E, Terzano, Mg, Tesser, F, Testa, L, Ticca, A, Ticozzi, N, Tiriticco, M, Tola, Mr, Tonietti, S, Trianni, G, Trojano, M, Trotta, F, Turatti, M, Ursino, E, Vanotti, A, Vercellino, M, Villani, A, Vitelli, E, Zambito Marsala, S, Zanette, G, Zarcone, D, Zimatore, G, Zoccolella, S., Magni E (ORCID:0000-0002-2235-2280), Benedetti, M. D., Pugliatti, M., Dalessandro, R., Beghi, E., Chio, A., Logroscino, G., Filippini, G., Galeotti, F., Massari, M., Santuccio, C., Raschetti R., Abruzzi L, Agazzi, E, Agostoni, E, Ambrogio, L, Amidei, S, Arbasino, C, Argentiero, V, Arnaboldi, M, Baldini, D, Barki, R, Bassi, P, Basso, F, Belcastro, V, Bellotti, M, Bersano, E, Besana, R, Bettoni, L, Bezzi, G, Bianconi, C, Bondavalli, M, Bonometti, A, Borghi, Am, Borsato, C, Bortolotto, S, Bottacchi, Ef, Bresolin, N, Bruno, S, Burlina, A, Cafasso, G, Callegarini, C, Calvo, A, Candeloro, E, Casano, A, Cattaneo, Si, Cavallo, R, Cheldi, A, Ciardo, G, Cirignotta, F, Clerici, Am, Clerici, R, Comi, G, Conti, R, Coppo, F, Covelli, V, Crespi, V, Currò Dossi, M, Curtò, Na, D'Adda, E, Dallocchio, C, D'Anna, S, De Massis, P, De Toni Franceschini, L, Di Vito, N, Didonè, G, Dileone, M, Donati, E, Dotta, M, Fazio, R, Federico, F, Ferrarese, C, Ferrazzini, F, Ferrero, B, Filosto, M, Frasson, E, Fusina, S, Galbussera, A, Gastaldo, E, Geda, C, Ghiglione, P, Giometto, B, Gionco, M, Giorgetti, A, Giussani, G, Gobbin, F, Grampa, G, Granieri, E, Greco, G, Guidetti, D, Guidi, C, Guidotti, M, Gusmaroli, G, Imperiale, D, Internò, S, Jann, S, La Spina, I, Leo, A, Leone, M, Leoni, S, Leotta, D, Lerario, R, Liotta, G, Livrea, P, Luda di Cortemiglio, E, Maggio, B, Magni, Eugenio, Magnoni, A, Maistrelli, J, Manca, D, Mandrioli, J, Manera, U, Marcello, N, Marchi, P, Marchini, C, Marconi, S, Mattioli, M, Mauro, A, Mazzaglia, G, Medici, D, Meineri, P, Meola, G, Micaglio, G, Michelucci, R, Michieli, G, Micieli, G, Minardi, C, Moglia, C, Monaco, S, Montanari, E, Moretto, G, Munerati, V, Mura, G, Mussutto, V, Nascimbene, C, Neri, W, Nichelli, P, Nobile-Orazio, E, Oddenino, E, Onorato, S, Padovani, A, Palermo, M, Papurello, Dm, Passarella, B, Pavesi, G, Penza, Mt, Perini, M, Perini, F, Perla, F, Perlotto, N, Perrone, P, Pignatta, P, Pisano, F, Poglio, F, Polo, A, Poloni, M, Porazzi, D, Pradotto, L, Previdi, P, Quatrale, R, Rasi, F, Ravasio, A, Ravetti, C, Repaci, M, Riccardi, T, Riguzzi, P, Rinaldi, R, Riva, M, Romeo, V, Romorini, A, Rosso, T, Rotondo, G, Sacquegna, T, Sanson, F, Santamato, V, Santoro, D, Sartori, V, Sasanelli, F, Savio, K, Serena, M, Silani, V, Silvestri, L, Simioni, V, Squintani, Gm, Suardelli, M, Tartagla, L, Terenghi, F, Terlizzi, E, Terzano, Mg, Tesser, F, Testa, L, Ticca, A, Ticozzi, N, Tiriticco, M, Tola, Mr, Tonietti, S, Trianni, G, Trojano, M, Trotta, F, Turatti, M, Ursino, E, Vanotti, A, Vercellino, M, Villani, A, Vitelli, E, Zambito Marsala, S, Zanette, G, Zarcone, D, Zimatore, G, Zoccolella, S., and Magni E (ORCID:0000-0002-2235-2280)

Abstract

To assess Guillain-Barre syndrome (GBS) incidence we relied on the Italian Network for the study of GBS (ITANG) established in 2010 in 7 Italian regions to analyse the association between influenza vaccination and GBS. Methods: All individuals aged ≥18 years, presenting with clinical manifestations that suggested GBS according to the universally accepted Asbury's diagnostic criteria (1990) were prospectively notified to a centralised database by ITANG neurologists over the period October 1, 2010-September 30, 2011. Through a telephone survey, 9 trained interviewers followed up the cases to diagnosis and then for 1 year since hospital discharge. Validation of case reporting was performed with the support of administrative data in 5 regions. Results: We found 365 cases fulfilling the definition for GBS or one of its variants over 19,846,068 population ≥18 years of age, yielding an annual incidence rate of 1.84 per 100,000 (95% CI 1.65-2.03), 2.30 (95% CI 1.99-2.60) in men and 1.41 (95% CI 1.18-1.64) in women. A highly significant peak of incidence was observed in February 2011 as compared to reference month (September 2011, rate ratio 3.3:1, p < 0.01). Conclusions: In Italy, GBS incidence was among the highest reported in Europe and higher than previously observed in Italian studies.

Published
2015

28. Otoacoustic Emissions

Author

Zimatore, G., Stanzial, D., and Orlando, Maria Patrizia

Subjects
ear structure, otorhinolaryngologic diseases, sense organs, acoustic emission
Abstract

In this chapter, we present a very special kind of acoustic emissions, coming from inside the cochlea and generated along the basilar membrane by the electro-motile (active) vibrations of outer hair cells of the organ of Corti. They are called OtoAcoustic Emissions (OAE) and are detected in the ear canal by means of microphones which are usually assembled as part of earphone-like probes. Since their discovery by Kemp [1], the study of otoacoustic emissions has become an hot topic both in basic and clinical research, due to OAE unique feature to inform directly about the normal and pathological functions of the cochlear receptors mechanisms, thus like the efficiency of the middle ear transmission chain.

Published
2013

29. Viable precursors of paroxysmal phenomena as detected by applying RQA to Acoustic Emission time series

Author

POSCOLIERI M., RAFANELLI C., and ZIMATORE G.

Subjects
AE sensor, paroxysmal events, precursors, AE time series, signal analysis, RQA
Abstract

Recurrence quantification analysis (RQA) represents a recent method for processing nonlinear time series, already addressed to different topics concerning earth sciences and others. RQA is applied in this work to analyze time series of acoustic emission (AE) triggered by Earth's crust phenomena, so to detect feasible precursors of catastrophic events. The AE records of rms values were acquired at two different sites, placed close to the Peteroa volcano (Argentina) and at Valsinni (Matera, Italy), considering two ultrasound frequencies (25 and 150 kHz) with 30-sec sampling rate. The preliminary results of the application of RQA to the AE data of Valsinni with respect to the L'Aquila earthquake (Italy, on April 6, 2009), and to those related to the activity of the Peteroa volcano (Argentina) are described and appear suited to stress relationships with an impending catastrophic event.

Published
2012

33. Recurrence Quantification Analysis of acoustic emission time series in the Peteroa volcano area (Argentina)

Author

ZIMATORE G., RAFANELLI C., and POSCOLIERI M.

Subjects
Friction Induced vibrations, Acoustic Emissions, Signal Analysis, Recurrence Quantification Analysis
Abstract

Non linear time series techniques are largely being applied in different disciplines, such as Earth Sciences, Astrophysics, Engineering, Economy, Physiology, and Neurosciences. One, in particular, Recurrence Quantification Analysis (RQA), appears quite promising for the analysis of complex systems. Moreover, it has recently been applied to investigate both acoustic emissions from rocky specimens and the dynamics of complex seismic processes. Whenever two objects are put in contact and let them slide with respect to each other, friction induced vibrations may occur. Examples are represented by active faults within seismogenic zones, narrow-banded noise of train wheels running along tight curves, friction in bearings, and micro-scale events in molecular physics. In this framework, the paper describes the application of RQA to the Passive Acoustic Emission (AE) signal released, at ultrasonic frequencies, by stressed rocks in the Earth's crust above a given threshold (event). The data record is represented by AE time series gathered, with 30 sec. of sampling rate, at the Peteroa Volcano monitoring station (Argentinean Andes). In these site AE data were collected by piezoelectric transducers, working at two ultrasonic frequencies, stuck to a rock. This way, a huge amount of data is available but the AE signal amplitude varies with the acoustic impedance, related to local rocks stress conditions and particularly sensitive to fracture density and water content. The aim of this work is to identify few descriptors that can explain the main characteristics of the AE signals and identify anomalies to be related to crustal stress modifications or, as in the Peteroa case study, paroxysmal volcanic activities or Earth's tides imprints.

Published
2012

34. RQA applied to Acoustic Emissions time series to pinpoint feasible precursors of catastrophic geological events

Author

POSCOLIERI M., RAFANELLI C., and ZIMATORE G.

Subjects
Acoustic Emissions, Signal Analysis, precursors of catastrophic events, condition monitoring / RQA, AE time series
Abstract

The paper deals with a relatively new technique, the Recurrence Quantification Analysis (RQA), a non-linear time series processing approach already utilized in different disciplines such as Economy, Physiology, Neurosciences, Earth Sciences, Astrophysics and Engineering. Here this method is applied to time series of Acoustic Emissions (AE) signals due to crustal movements, in order to show up possible precursors of catastrophic events. The AE records have been collected, at two different ultrasound frequencies (25 and 150 kHz) and with 30 sec. of sampling rate, in two sites located at Valsinni (Potenza, Italy) and nearby the Peteroa volcano (Argentina). The preliminary results of RQA applied to these AE time series before the earthquake of L'Aquila (Italy, on April 6, 2009), and those concerning the activity of the Andean volcano are shown and seem quite suitable for highlighting incoming paroxysms.

Published
2012

36. Development and validation of a patient self-assessed questionnaire on satisfaction with communication of the multiple sclerosis diagnosis

Author

Solari, A, Mattarozzi, K, Vignatelli, L, Giordano, A, Russo, P, Messmeruccelli, M, D'Alessandro, R, Pucci, E, Martinelli, V, Uccelli, Mm, Borreani, C, Trojano, M, Heesen, C, Mancardi, Gl, Milanese, C, Galimberti, S, Calabrese, D, Ferrari, G, Confalonieri, P, Mantegazza, R, Maggi, L, Colombo, B, Esposito, F, Moiola, L, Rodegher, M, Radaelli, M, Granella, F, Immovilli, P, Dalla Bella, E, Lugaresi, A, De Luca, G, Mattoscio, M, Di Ioia, M, Travaglini, D, Farina, D, Zimatore, G, Plasmati, I, Tortorella, C, Orsolamalpighi, S, Guidolin, L, Leone, M, Motti, L, Tola, Mr, Montanari, E, Guareschi, A, Pesci, I, Pattini, M, Feo, C, Torricelli, L, Santangelo, M, Stecchi, S, Scandellari, C, Balugani, R, La Mola, L, Montagna, P, Pizza, F, Avoni, P, Baldin, E, Delaj, L, Rinaldi, R, Baldi, E, Caniatti, L, Milani, P, Mussuto, V, Manzoni, M, Casmiro, M, Fiorani, L, Galeotti, M, Guerrini, C, Neri, W, Mambelli, L, Malagù, S, Naldi, P, Calzoni, S, Collimedaglia, L, Pietrolongo, E, Di Tommaso, V, Pace, M, Benedetti, M, Rossi, F, Pastoretrossello, M, Faccioli, L, Spinardi, L., Solari A., Mattarozzi K., Vignatelli L., Giordano A., Russo P.M., Uccelli M.M., D'Alessandro R., Montagna P., Pizza F., Avoni P., Baldin E., Delaj L., SIMS-Trial group, and GERONIMUS group.

Subjects
Questionnaires, Adult, Male, medicine.medical_specialty, Neurology, Multiple Sclerosis, Psychometrics, Adolescent, Adolescent, Adult, Aged, Cognition, physiology, Communication, Disease Progression, Early Diagnosis, Factor Analysis, Statistical, Female, Humans, Male, Middle Aged, Multiple Sclerosis, psychology, Patient Satisfaction, Physician-Patient Relations, Psychiatric Status Rating Scales, Questionnaires, Reproducibility of Results, Young Adult, Newly diagnosed, psychology, Young Adult, Patient satisfaction, DIAGNOSIS COMMUNICATION, Cognition, Surveys and Questionnaires, medicine, Humans, Aged, Psychiatric Status Rating Scales, Physician-Patient Relations, PSYCHOMETRICS, business.industry, Multiple sclerosis, Communication, Reproducibility of Results, Statistical, Middle Aged, medicine.disease, Surgery, Clinical trial, Early Diagnosis, Patient Satisfaction, physiology, PATIENT-REPORTED OUTCOMES, Physical therapy, Disease Progression, Female, Neurology (clinical), business, Factor Analysis, Statistical, Factor Analysis
Abstract

Background: We describe the development and clinical validation of a patient self-administered tool assessing the quality of multiple sclerosis diagnosis disclosure. Method: A multiple sclerosis expert panel generated questionnaire items from the Doctor’s Interpersonal Skills Questionnaire, literature review, and interviews with neurology inpatients. The resulting 19-item Comunicazione medico-paziente nella Sclerosi Multipla (COSM) was pilot tested/debriefed on seven patients with multiple sclerosis and administered to 80 patients newly diagnosed with multiple sclerosis. The resulting revised 20-item version (COSM-R) was debriefed on five patients with multiple sclerosis, field tested/debriefed on multiple sclerosis patients, and field tested on 105 patients newly diagnosed with multiple sclerosis participating in a clinical trial on an information aid. The hypothesized monofactorial structure of COSM-R section 2 was tested on the latter two groups. Results: The questionnaire was well accepted. Scaling assumptions were satisfactory in terms of score distributions, item—total correlations and internal consistency. Factor analysis confirmed section 2’s monofactorial structure, which was also test—retest reliable (intraclass correlation coefficient [ICC] 0.73; 95% CI 0.54—0.85). Section 1 had only fair test—retest reliability (ICC 0.45; 95% CI 0.12—0.69), and three items had 8—21% missed responses. Conclusions: COSM-R is a brief, easy-to-interpret MS-specific questionnaire for use as a health care indicator.

Published
2010

37. Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis

Author

Ernst Wilhelm, Radue, William, H. Stuart, Peter, A. Calabresi, Christian, Confavreux, Steven, L. Galetta, Richard, A. Rudick, Fred, D. Lublin, Bianca, Weinstock Guttman, Daniel, R. Wynn, Elizabeth, Fisher, Athina, Papadopoulou, Frances, Lynn, Michael, A. Panzara, Alfred, W. Sandrock, For, the SENTINEL Investigators including F. Fazekas, Enzinger, C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, E., Egg, R., Deisenhammer, F., Decoo, D, Lampaert, J., Bartholome, E., Bier, J., Stenager, E., Rasmussen, M., Binzer, M., Shorsh, K., Christensen, M., Ravnborg, M., Soelberg Sørensen, P., Blinkenberg, M., Petersen, B., Hansen, H. J., Bech, E., Petersen, T., Kirkegaard, M., Finland:, J. Eralinna, Ruutiainen, J., Soilu Hänninen, M., Säkö, E., Laaksonen, M., Reunanen, M., Remes, A., Keskinarkaus, I., Moreau, T., Noblet, M., Rouaud, O., Couvreur, G., Edan, G., Lepage, E., Drapier, S., De Burghgraeve, V., Yaouanq, J., Merienne, M., Cahagne, V., Gout, O., Deschamps, R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, J., Stojkovic, T., Griffié, G., Engles, Ferriby, D., Debouverie, M., Pittion Vouyouvitch, S., Lacour, J. C., Pelletier, J., Feuillet, L., Suchet, L., Dalecky, A., Tammam, D., Lubetzki, C., Youssov, K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, D., Renouil Guy, N., Cesaro, P., Degos, F., Benisty, S., Rumbach, L., Decavel, P., Confavreux, C., Blanc, S., Aubertin, P., Riche, G., Brochet, B., Ouallet, J. C., Anne, O., Menck, S., Grupe, Guttman, Lensch, E., Fucik, E., Heitmann, S., Hartung, H. P., Schröter, M., Kurz, F. M. W., Heidenreich, F., Trebst, C., Pul, R., Hohlfeld, R., Krumbholz, M., Pellkofer, H., Haas, J., Segert, A., Meyer, R., Anagnostou, P., Kabus, C., Poehlau, D., Schneider, K., Hoffmann, V., Zettl, U., Steinhagen, V., Adler, S., Steinbrecher E. Rothenfusser Körber, A. Steinbrecher E. Rothenfusser Körber, Zellner, Baum, K., Günther, A., Bläsing, H., Stoll, G., Gold, R., Bayas, A., Kleinschnitz, C., Limmroth, V., Katsarava, Z., Kastrup, O., Haller, P., Stoeve, S., Höbel, D., Oschmann, P., Voigt, K., Burger, C. V., Israel:, O. Abramsky, Karusiss, D., Achiron, A., Kishner, I., Stern, Y., Sarove Pinhas, I., Dolev, M., Magalashvili, D., Pozzili, : C., Lenzi, D., Scontrini, A., Millefiorini, E., Buttinelli, C., Gallo, P., Ranzato, F., Tiberio, M., Perini, P., Laroni, Alice, Marrosu, M., Cocco P. Marchi, E. Cocco P. Marchi, Spinicci, G., Massole, S., Mascia, M., Floris, G., Trojano, M., Bellacosa, A., Paolicelli, D., Bosco Zimatore, G., Simone, I. L., Giorelli, M., Di Monte, E., Mancardi, GIOVANNI LUIGI, Pizzorno, M., Murialdo, A., Narciso, E., Capello, A., Comi, G., Martinelli, V., Rodegher, M., Esposito, F., Colombo, B., Rossi, P., Polman, C. H., Jasperse, M. M. S., Zwemmer, J. N. P., Nielsen, J., Kragt, J. J., Jongen, P. J. H., De Smet, E., Tacken, H., Frequin, S. T. F. M., Siegers, H. P., Mauser, H. W., Fernandez Fernandez, O., León, A., Romero, F., Alonso, A., Tamayo, J., Montalban, X., Nos, C., Pelayo, R., Tellez, N., Rio, J., Tintore, M., Arbizu, T., Romero, L., Moral, E., Martinez, S., Switzerland:, L. Kappos, Achtnichts, L., Wilmes, S., Turkey:, R. Karabudak, Kurne, A., Erdem, S., Siva, A., Saip, S., Altintas, A., Atamer, A., Eraksoy, M., Bilgili, F., Topcular, B., Giovannoni, G., Lim, E. T., Lava, N., Murnane, M., Dentinger, M., Zimmerman, E., Reiss, M., Gupta, V., Scott, T., Brillman, J., Kunschner, L., Wright, D., Perel, A., Babu, A., Rivera, V., Killian, J., Hutton, G., Lai, E., Picone, M., Cadivid, D., Kamin, S., Shanawani, M., Gauthier, S., Morgan, A., Buckle, G., Margolin, D., Weinstock Guttman, B., Kwen, P. L., Garg, N., Munschauer, F., Khatri, B., Rassouli, M., Saxena, V., Ahmed, A., Turner, A., Fox, E., Couch, C., Tyler, R., Horvit, A., Fodor, P., Humphries, S., Wynn, D., Nagar, C., O'Brien, D., Allen, N., Turel, A., Friedenberg, S., Carlson, J., Hosey, J., Crayton, H., Richert, J., Tornatore, C., Sirdofsky, M., Greenstein, J., Shpigel, Y., Mandel, S., Adbelhak, T., Schmerler, M., Zadikoff, C., Rorick, M., Reed, R., Elias, S., Feit, H., Angus, E., Sripathi, N., Herbert, J., Kiprovski, K., Qu, X., Del Bene, M., Mattson, D., Hingtgen, C., Fleck, J., Horak, H., Javerbaum, J., Elmore, R., Garcia, E., Tasch, E., Gruener, G., Celesia, G., Chawla, J., Miller, A., Drexler, E., Keilson, M., Wolintz, R., Drasby, E., Muscat, P., Belden, J., Sullivan, R., Cohen, J., Stone, L., Marrie, R. A., Fox, R., Hughes, B., Babikian, P., Jacoby, M., Doro, J., Puricelli, M., Rossman, H., Boudoris, W., Belkin, M., Pierce, R., Eggenberger, E., Birbeck, G., Martin, J., Kaufman, D., Stuart, W., English, J. B., Stuart, D. S., Gilbert, R. W., Kaufman, M., Putman, S., Diedrich, A., Follmer, R., Pelletier, D., Waubant, E., Cree, B., Genain, C., Goodin, D., Guarnaccia, J., Patwa, H., Rizo, M., Kitaj, M., Blevins, J., Smith, T., Mcgee, F., Honeycutt, W., Brown, M., Isa, A., Nieves Quinones, D., Krupp, L., Smiroldo, J., Zarif, M., Perkins, C., Sumner, A., Fisher, A., Gutierrez, Jacoby, R., Svoboda, S., Dorn, D., Groeschel, A., Steingo, B., Kishner, R., Cohen, B., Melen, O., Simuni, T., Zee, P., Cohan, S., Yerby, M., Hendin, B., Levine, T., Tamm, H., Travis, L. H., Freedman, S. M., Tim, R., Ferrell, W., Stefoski, D., Stevens, S., Katsamakis, G., Topel, J., Ko, M., Gelber, D., Fortin, C., Green, B., Logan, W., Carpenter, D., Temple, L., Sadiq, S., Sylvester, A., Sim, G., Mihai, C., Vertino, M., Jubelt, B., Mejico, L., Phillips, J. T., Martin, A., Heitzman, D., Greenfield, C. F., Riskind, P., Cabo, A., Paskavitz, J., Moonis, M., Bashir J. Brockington, K. Bashir J. Brockington, Nicholas, A., Slaughter, R., Archer S. Harik, R. Archer S. Harik, Haddad, N., Pippenger, M. A., Van den Noort, S., Thai, G., Olek, M., Demetriou, M., Shin, R., Calabresi, P., Rus, H., Bever, C., Johnson, K., Sheremata, W., Delgado, S., Sherbert, R., Herndon, R., Uschmann, H., Chandler, A., Markowitz, C., Jacobs, D., Balcer, L., Mitchell, G., Chakravorty, S., Heyman, R., Stauber, Z., Goodman, A., Segal, B., Schwid, S., Samkoff, L., Levin, M., Jacewicz, M., Menkes, D., Pulsinelli, W., Frohman, E., Racke, M., Hawker, K., Ulrich, R., Panitch, H., Hamill, R., Tandon, R., Dulaney, E., Simnad, V., Miller, J., Wooten, G. F., Harrison, M., Bowen, J., Doherty, M., Wundes, A., Garden, G. A., Distad, J., Kachuck, N., Berkovich, R., Burnett, M., Sahai, S., Bandari, D., Weiner, L., Storey, J. R., Beesley, B., Hart, D., Moses, H., Sriram, S., Fang, J., O'Duffy, A., Kita, M., Taylor, L., Elliott, M., Roberts, J., Jeffery, D., Maxwell, S., Lefkowitz, D., Kumar, S., Sinclair, M., Neurology, and NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Adolescent, Relapsing-Remitting, Placebo, Antibodies, Monoclonal, Humanized, Gastroenterology, Antibodies, Central nervous system disease, Pharmacotherapy, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, pathology/therapy, Drug Therapy, Internal medicine, Monoclonal, Medicine, Humans, Immunologic Factors, Humanized, medicine.diagnostic_test, business.industry, Multiple sclerosis, Patient Selection, Interferon beta-1a, Antibodies, Monoclonal, Brain, Magnetic resonance imaging, Interferon-beta, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Surgery, Treatment Outcome, Neurology, therapeutic use, Combination, Drug Therapy, Combination, pathology, Female, Neurology (clinical), Adolescent, Adult, Antibodies, Humanized, Antibodies, therapeutic use, Brain, pathology, Drug Therapy, Combination, Female, Humans, Immunologic Factors, therapeutic use, Interferon-beta, therapeutic use, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, pathology/therapy, Patient Selection, Treatment Outcome, business, medicine.drug
Abstract

The SENTINEL study showed that the addition of natalizumab improved outcomes for patients with relapsing multiple sclerosis (MS) who had experienced disease activity while receiving interferon beta-1a (IFNbeta-1a) alone. Previously unreported secondary and tertiary magnetic resonance imaging (MRI) measures are presented here. Patients received natalizumab 300 mg (n=589) or placebo (n=582) intravenously every 4 weeks plus IFNbeta-1a 30 microg intramuscularly once weekly. Annual MRI scans allowed comparison of a range of MRI end points versus baseline. Over 2 years, 67% of patients receiving natalizumab plus IFNbeta-1a remained free of new or enlarging T2-lesions compared with 30% of patients receiving IFNbeta-1a alone. The mean change from baseline in T2 lesion volume over 2 years decreased in patients receiving natalizumab plus IFNbeta-1a and increased in those receiving IFNbeta-1a alone (-277.5mm(3) versus 525.6mm(3); p0.001). Compared with IFNbeta-1a alone, add-on natalizumab therapy resulted in a smaller increase in mean T1-hypointense lesion volume after 2 years (1821.3mm(3) versus 2210.5mm(3); p0.001), a smaller mean number of new T1-hypointense lesions over 2 years (2.3 versus 4.1; p0.001), and a slower rate of brain atrophy during the second year of therapy (-0.31% versus -0.40%; p=0.020). Natalizumab add-on therapy reduced gadolinium-enhancing, T1-hypointense, and T2 MRI lesion activity and slowed brain atrophy progression in patients with relapsing MS who experienced disease activity despite treatment with IFNbeta-1a alone.

Published
2010

39. Real-life impact of early interferon beta therapy in relapsing multiple sclerosis

Author

Trojano, M., Pellegrini, F., Paolicelli, D., Fuiani, A., Zimatore, G., Tortorella, C., Simone, I., Patti, F., Ghezzi, A., Zipoli, V., Rossi, P., Pozzilli, C., Salemi, G., Lugaresi, A., Bergamaschi, R., Millefiorini, E., Clerico, M., Lus, G., Vianello, M., Avolio, C., Cavalla, P., Lepore, V., Livrea, P., Comi, G., Amato, M., Di Monte, E., Iaffaldano, P., Direnzo, V., D'Onghia, M., Lo Fermo, S., Messina, S., D'Amico, E., Rizzo, A., Zaffaroni, M., Portaccio, E., Martinelli, V., Prosperini, L., Onesti, E., Aridon, P., D'Amelio, M., Ragonese, P., De Luca, G., Farina, D., Di Tommaso, V., Tavazzi, E., Bargiggia, V., Crivelli, P., Cortese, A., Di Rezze, S., Durastanti, V., Alfieri, G., Rosellini, I., Modesto, M., Notariello, M., Tortorella, P., Trojano M, Pellegrini F, Paolicelli D, Fuiani A, Zimatore GB, Tortorella C, Simone IL, Patti F, Ghezzi A, Zipoli V, Rossi P, Pozzilli C, Salemi G, Lugaresi A, Bergamaschi R, Millefiorini E, Clerico M, Lus G, Vianello M, Avolio C, Cavalla P, Lepore V, Livrea P, Comi G, Amato MP, Di Monte E, Iaffaldano P, Direnzo V, D'Onghia M, Lo Fermo S, Messina S, D'Amico E, Rizzo A, Zaffaroni M, Portaccio E, Martinelli V, Prosperini L, Onesti E, Aridon P, D'Amelio M, Ragonese P, De Luca G, Farina D, Di Tommaso V, Tavazzi E, Bargiggia V, Crivelli P, Cortese A, Di Rezze S, Durastanti V, Alfieri G, Rosellini I, Modesto M, Notariello M, Tortorella P, Trojano, M, Pellegrini, F, Paolicelli, D, Fuiani, A, Zimatore, Gb, Tortorella, C, Simone, Il, Patti, F, Ghezzi, A, Zipoli, V, Rossi, P, Pozzilli, C, Salemi, G, Lugaresi, Alessandra, Bergamaschi, R, Millefiorini, E, Clerico, M, Lus, G, Vianello, M, Avolio, C, Cavalla, P, Lepore, V, Livrea, P, Comi, G, and Amato, Mp

Subjects
Adult, Male, Time Factors, Multiple Sclerosis, Interferon beta, Interferon-beta, Cohort Studies, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Treatment Outcome, observational study, multiple sclerosis, interferon, treatment, early, Sickness Impact Profile, Multiple Sclerosi, Quality of Life, Humans, Female, Settore MED/26 - Neurologia, Prospective Studies, Follow-Up Studies
Abstract

OBJECTIVE: Recent findings support greater efficacy of early vs. delayed interferon beta (IFNbeta) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to evaluate the effectiveness of early IFNbeta treatment in definite relapsing-remitting MS (RRMS) and to assess the optimal time to initiate IFNbeta treatment with regard to the greatest benefits on disability progression. METHODS: A cohort of 2,570 IFNbeta-treated RRMS patients was prospectively followed for up to 7 years in 15 Italian MS Centers. A Cox proportional hazards regression model adjusted for propensity score (PS) quintiles was used to assess differences between groups of patients with early vs. delayed IFNbeta treatment on risk of reaching a 1-point progression in the Expanded Disability Status Scale (EDSS) score, and the EDSS 4.0 and 6.0 milestones. A set of PS-adjusted Cox hazards regression models were calculated according to different times of treatment initiation (within 1 year up to within 5 years from disease onset). A sensitivity analysis was performed to assess the robustness of findings. RESULTS: The lowest hazard ratios (HRs) for the three PS quintiles-adjusted models were obtained by a cutoff of treatment initiation within 1 year from disease onset. Early treatment significantly reduced the risk of reaching a 1-point progression in EDSS score (HR = 0.63; 95% CI = 0.48-0.85; p < 0.002), and the EDSS 4.0 milestone (HR = 0.56; 95% CI = 0.36-0.90; p = 0.015). Sensitivity analysis showed the bound of significance for unmeasured confounders. INTERPRETATION: Greater benefits on disability progression may be obtained by an early IFNbeta treatment in RRMS.

Published
2009

44. The incidence and significance of anti-natalizumab antibodies: results from AFFIRM and SENTINEL

Author

Calabresi, Pa, Giovannoni, G, Confavreux, C, Galetta, Sl, Havrdova, E, Hutchinson, M, Kappos, L, Miller, Dh, O'Connor, Pw, Phillips, Jt, Polman, Ch, Radue, Ew, Rudick, Ra, Stuart, Wh, Lublin, Fd, Wajgt, A, Weinstock Guttman, B, Wynn, Dr, Lynn, F, Panzara, Ma, Affirm, Investigators, Fazekas, SENTINEL Investigators including: F., Enzinger, C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, E., Egg, R., Eisenhammer, F., Decoo J. Lampaert, D. Decoo J. Lampaert, Bartholome J. Bier, E. Bartholome J. Bier, Stenager, E., Rasmussen, M., Binzer, M., Shorsh, K., Christensen, M., Ravnborg, M., Soelberg Sørensen, P., Blinkenberg, M., Petersen, B., Hansen, H. J., Bech, E., Petersen, T., Kirkegaard, M., Eralinna, J., Ruutiainen, J., Soilu Hänninen, M., Säkö, E., Laaksonen, M., Reunanen, M., Remes, A., Keskinarkaus, I., Moreau, T., Noblet, M., Rouaud, O., Couvreur, G., Edan, G., Lepage, E., Drapier, S., De Burghgraeve, V., Yaouanq, J., Merienne, M., Cahagne, V., Gout, O., Deschamps, R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, J., Stojkovic, T., Griffié, G., Engles, A., Ferriby, D., Debouverie, M., Pittionvouyouvitch, S., Lacour, J. C., Pelletier, J., Feuillet, L., Suchet, L., Dalecky, A., Tammam, D., Lubetzki, C., Youssov, K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, D., Renouil Guy, N., Cesaro, P., Degos, F., Benisty, S., Rumbach P. Decavel, L. Rumbach P. Decavel, Confavreux, C., Blanc, S., Aubertin, P., Riche, G., Brochet, B., Ouallet, J. C., Anne, O., Menck, S., Grupe, A., Guttman, E., Lensch, E., Fucik, E., Heitmann, S., Hartung, H. P., Schröter, M., Kurz, F. M. W., Heidenreich, F., Trebst, C., Pul, R., Hohlfeld, R., Krumbholz, M., Pellkofer, H., Haas, J., Segert, A., Meyer, R., Anagnostou, P., Kabus, C., Poehlau, D., Schneider, K., Hoffmann, V., Zettl, U., Steinhagen, V., Adler, S., Steinbrecher, A., Rothenfusser Körber, E., Zellner, R., Baum, K., Günther, A., Bläsing, H., Stoll, G., Gold, R., Bayas, A., Kleinschnitz, C., Limmroth, V., Katsarava, Z., Kastrup, O., Haller, P., Stoeve, S., Höbel, D., Oschmann, P., Voigt, K., Burger, C. V., Abramsky D. Karusiss, O. Abramsky D. Karusiss, Achiron, A., Kishner, I., Stern, Y., Sarove Pinhas, I., Dolev, M., Magalashvili, D., Pozzili, C., Lenzi, D., Scontrini, A., Millefiorini, E., Buttinelli, C., Gallo, P., Ranzato, F., Tiberio, M., Perini, P., Laroni, Alice, Marrosu, M., Cocco P. Marchi, E. Cocco P. Marchi, Spinicci, G., Massole, S., Mascia, M., Floris, G., Trojano, M., Bellacosa, A., Paolicelli, D., Bosco Zimatore, G., Simone, I. L., Giorelli, M., Di Monte, E., Mancardi, GIOVANNI LUIGI, Pizzorno, M., Murialdo, A., Narciso, E., Capello, A., Comi, G., Martinelli, V., Rodegher, M., Esposito, F., Colombo, B., Rossi, P., Polman, C. H., Jasperse, M. M. S., Zwemmer, J. N. P., Nielsen, J., Kragt, J. J., Jongen, P. J. H., De Smet, E., Tacken, H., Frequin, S. T. F. M., Siegers, H. P., Mauser, H. W., Fern ez Fern ez, O., León, A., Romero, F., Alonso, A., Tamayo, J., Montalban, X., Nos, C., Pelayo, R., Tellez, N., Rio, J., Tintore, M., Arbizu, T., Romero, L., Moral, E., Martinez, S., Kappos, L., Achtnichts, L., Wilmes, S., Karabudak, R., Kurne, A., Erdem, S., Siva, A., Saip, S., Altintas, A., Atamer, A., Eraksoy, M., Bilgili, F., Topcular, B., Giovannoni ET Lim, G. Giovannoni E. T. Lim, Lava, N., Murnane, M., Dentinger, M., Zimmerman, E., Reiss V. Gupta, M. Reiss V. Gupta, Scott, T., Brillman, J., Kunschner, L., Wright, D., Perel A. Babu, A. Perel A. Babu, Rivera, V., Killian, J., Hutton, G., Lai, E., Picone, M., Cadivid, D., Kamin, S., Shanawani, M., Gauthier, S., Morgan, A., Buckle, G., Margolin, D., Weinstock Guttman, B., Kwen, P. L., Garg, N., Munschauer, F., Khatri, B., Rassouli, M., Saxena, V., Ahmed, A., Turner, A., Fox, E., Couch, C., Tyler, R., Horvit, A., Fodor S. Humphries, P. Fodor S. Humphries, Wynn, D., Nagar, C., O’Brien, D., Allen, N., Turel, A., Friedenberg, S., Carlson, J., Hosey, J., Crayton, H., Richert, J., Tornatore, C., Sirdofsky, M., Greenstein, J., Shpigel, Y., S. M, El, Adbelhak, T., Schmerler, M., Zadikoff, C., Rorick, M., Reed, R., Elias, S., Feit, H., Angus, E., Sripathi, N., Herbert, J., Kiprovski, K., Qu, X., Del Bene, M., Mattson, D., Hingtgen, C., Fleck, J., Horak, H., Kaiser, J. Javerbaum, Elmore, R., Garcia, E., Tasch, E., Gruener, G., Celesia, G., Chawla, J., Miller, A., Drexler, E., Keilson, M., Wolintz, R., Drasby, E., Muscat, P., Belden, J., Sullivan, R., Cohen, J., Stone, L., Marrie, R. A., Fox, R., Hughes, B., Babikian, P., Jacoby, M., Doro, J., Puricelli, M., Rossman, H., Boudoris, W., Belkin, M., Pierce, R., Eggenberger, E., Birbeck, G., Martin, J., Kaufman, D., Stuart, W., English, J. B., Stuart, D. S., Gilbert, R. W., Kaufman, M., Putman, S., Diedrich, A., Follmer, R., Pelletier, D., Waubant, E., Cree, B., Genain, C., Goodin, D., Guarnaccia, J., Patwa, H., Rizo, M., Kitaj, M., Blevins, J., Smith, T., Mcgee, F., Honeycutt, W., Brown, M., Isa, A., Nieves Quinones, D., Krupp, L., Smiroldo, J., Zarif, M., Perkins, C., Sumner, A., Fisher, A., Gutierrez, A., Jacoby, R., Svoboda, S., Dorn, D., Groeschel, A., Steingo R. Kishner, B. Steingo R. Kishner, Cohen, B., Melen, O., Simuni, T., Zee, P., Cohan M. Yerby, S. Cohan M. Yerby, Hendin, B., Levine, T., Tamm, H., Travis, L. H., Freedman, S. M., Tim, R., Ferrell, W., Stefoski, D., Stevens, S., Katsamakis, G., Topel, J., KoD Gelber C. Fortin, M. K. o. D. Gelber C. Fortin, Green, B., Logan, W., Carpenter, D., Temple, L., Sadiq, S., Sylvester, A., Sim, G., Mihai, C., Vertino, M., Jubelt, B., Mejico, L., Phillips, J. T., Martin, A., Heitzman, D., Greenfield, C. F., Riskind, P., Cabo, A., Paskavitz, J., Moonis, M., Bashir, K., Brockington, J., Nicholas, A., Slaughter, R., Archer, R., Harik, S., Haddad, N., Pippenger, M. A., Van den Noort, S., Thai, G., Olek, M., Demetriou, M., Shin, R., Calabresi, P., Rus, H., Bever, C., Johnson, K., Sheremata, W., Delgado, S., Sherbert, R., Herndon, R., Uschmann, H., Ch ler, A., Markowitz, C., Jacobs, D., Balcer, L., Mitchell, G., Chakravorty, S., Heyman, R., Stauber, Z., Goodman, A., Segal, B., Schwid, S., Samkoff, L., Levin, M., Jacewicz, M., Menkes, D., Pulsinelli, W., Frohman, E., Racke, M., Hawker, K., Ulrich, R., Panitch, H., Hamill, R., R. T, On, Dulaney, E., Simnad, V., Miller, J., Wooten, G. F., Harrison, M., Bowen, J., Doherty, M., Wundes, A., Garden, G. A., Distad, J., Kachuck, N., Berkovich, R., Burnett, M., Sahai, S., Ari, D. B, Weiner, L., Storey, J. R., Beesley, B., Hart, D., Moses, H., Sriram, S., Fang, J., O’Duffy, A., Kita, M., Taylor, L., Elliott, M., Roberts, J., Jeffery, D., Maxwell, S., Lefkowitz, D., Kumar, S., Sinclair EW Radue, M. S. i. n. c. l. a. i. r. E. W. Radue, de Vera, A., Bacelar, O., Kuster, P., and Kappos, L. .

Subjects
medicine.medical_specialty, Multiple Sclerosis, Enzyme-Linked Immunosorbent Assay, Relapsing-Remitting, Antibodies, Monoclonal, Humanized, Gastroenterology, Antibodies, law.invention, Disability Evaluation, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, Randomized controlled trial, Double-Blind Method, law, Antibody Specificity, Internal medicine, Monoclonal, medicine, Secondary Prevention, Humans, Adverse effect, Antibodies, Blocking, Humanized, Antibodies, Monoclonal, Brain, Flow Cytometry, Interferon-beta, Magnetic Resonance Imaging, Placebo Effect, Treatment Outcome, Neuroscience (all), Expanded Disability Status Scale, business.industry, Multiple sclerosis, Incidence (epidemiology), Interferon beta-1a, medicine.disease, Blocking, Multiple sclerosis functional composite, Immunology, Neurology (clinical), business, medicine.drug
Abstract

Objective: To determine the incidence and clinical effects of antibodies that develop during treatment with natalizumab. Methods: In two randomized, double-blind, placebo-controlled studies (natalizumab safety and efficacy in relapsing remitting multiple sclerosis [MS, AFFIRM] and safety and efficacy of natalizumab in combination with interferon β-1a [INFβ1a] in patients with relapsing remitting MS [SENTINEL]) of patients with relapsing multiple sclerosis, blood samples were obtained at baseline and every 12 weeks to determine the presence of antibodies against natalizumab. Antibodies to natalizumab were measured using an ELISA. Patients were categorized as “transiently positive” if they had detectable antibodies (≥0.5 μg/mL) at a single time point or “persistently positive” if they had antibodies at two or more time points ≥6 weeks apart. Results: In the AFFIRM study, antibodies were detected in 57 of 625 (9%) of natalizumab-treated patients: Twenty (3%) were transiently positive and 37 (6%) were persistently positive. Persistently positive patients showed a loss of clinical efficacy as measured by disability progression ( p ≤ 0.05), relapse rate ( p = 0.009), and MRI ( p ≤ 0.05) compared with antibody-negative patients. In transiently positive patients, full efficacy was achieved after approximately 6 months of treatment, the time when patients were becoming antibody negative. The incidence of infusion-related adverse events was significantly higher in persistently positive patients. Results of SENTINEL were similar to AFFIRM, except with regard to sustained disability progression; differences between persistently positive and antibody-negative patients were not statistically significant. Conclusions: The incidence of persistent antibody positivity associated with natalizumab is 6%. Reduced clinical efficacy is apparent in persistently positive patients. Patients with a suboptimal clinical response or persistent infusion-related adverse events should be considered for antibody testing. GLOSSARY: BLQ = below the limit of quantification; EDSS = Expanded Disability Status Scale; Gd+ = gadolinium enhancing; IFNβ1a = interferon β-1a; MS = multiple sclerosis; MSFC = multiple sclerosis functional composite; OD = optical density.

Published
2007

45. Health-related quality of life in multiple sclerosis: Effects of natalizumab

Author

Rudick, R. A., Miller, D., Hass, S., Hutchinson, M, Calabresi, P. A., Confavreux, C., Galetta, S. L., Giovannoni, G., Havrdova, E., Kappos, L., Lublin, F. D., Miller, D. H., O'Connor, P. W., Phillips, J. T., Polman, C. H., Radue, Ew, Stuart, W. H., Wajgt, A., Weinstock Guttman, B., Wynn, D. R., Lynn, F., Panzara, M. A., Affirm, Macdonell, SENTINEL Investigators including: R., Hughes, A., Taylor, I., Lee, Y. C., Ma, H., King, J., Kilpatrick, T., Butzkueven, H., Marriott, M., Pollard, J., Spring, P., Spies, J., Barnett, M., Dehaene, I., Vanopdenbosch, L., D’Hooghe, M., Van Zandijcke, M., Derijck, O., Seeldrayers, P., Jacquy, J., Piette, T., De Cock, C., Medaer, R., Soors, P., Vanroose, E., Vanderhoven, L., Nagels, G., Dubois, B., Deville, M. C., D’Haene, R., Jacques, F., Hallé, D., Gagnon, S., Likavcan, E., Murray, T. J., Bhan, V., Mackelvey, R., Maxner, C. E., Christie, S., Giaccone, R., Guzman, D. A., Melanson, M., Esfahani, F., Gomori, A. J., Nagaria, M. H., Grand’Maison, F., Berger, L., Nasreddine, Z., Duplessis, M., Brunet, D., Jackson, A., Pari, G., O’Connor, P., Gray, T., Hohol, M., Marchetti, P., Lee, L., Murray, B., Sahlas, J., Perry, J., Devonshire, V., Hooge, J., Hashimoto, S., Oger, J., Smyth, P., Rice, G., Kremenchutzky, M., Stourac, P., Kadanka, Z., Benesova, Y., Niedermayerova, I., Meluzinova, E., Marusic, P., M, Bojar, Zarubova, K., Houzvicková, E., Piková, J., Talab, R., Faculty, Hospital Olomouc, Olomouc, B. Muchova, Urbánek, K, Kettnerova, Z., Mares, J., Otruba, P., Zapletalová, O., Hradilek, P., Ddolezil, D. Dolezil, Woznicova, I., Höfer, R., Ambler J. Fiedler, Z. Ambler J. Fiedler, Sucha, J., Matousek, V., Rektor, I., Dufek, M., Mikulik, R., Mastik, J., Tyrlikova, I., General, Teaching Hospital, Prague, E. Havrdová, Horakova, D., Kalistová, H., Týblová, M., Ehler, E., Novotná, A., Geier, P., Soelberg Sorensen, P., Ravnborg, M., Petersen, B., Blinkenberg, M., Färkkilä, M., Harno, H., Kallela, M., Häppölä, O., Elovaara, I., Kuusisto, H., Ukkonen, M., Peltola, J., Palmio, J., Pelletier, J., Feuillet, L., Suchet, L., Dalecky, A., Tammam, D., Edan, G., Le Page, E., Mérienne, M., Yaouanq, J., Clanet, M., Mekies, C., Azais Vuillemin, C., Senard, A., Lau, G., Steinmetz, G., Warter V. Wolff, J. Warter V. Wolff, Fleury, M., Tranchant, C., Stark, E., Buckpesch Heberer, U., Henn, K. H., Skoberne, T., Schimrigk, S., Hellwig, K., Brune, N., Weiller, C., Gbadamosi, J., Röther, J., Heesen, C., Buhmann, C., Karageorgiou, C., Korakaki, D., Giannoulis, D. r., Tsiara, S., Thomaides, T., Thomopoulos, I., Papageorgiou, H., Armakola, F., Komoly, S., Rózsa, C., Matolcsi, J., Szabó, G. y., Molnár, B., Lovas, G., Dioszeghy, P., Szulics, P., Magyar, Z., Incze, J., Farkas, J., Clemens, B., Kánya, J., Valicskó, Z. s., Bense, E., Nagy, Z. s., Geréby, G., Perényi, J., Simon, Z. s., Szapper, M., Gedeon, L., Csanyi, A., Rum, G., Lipóth, S., Szegedi, A., Jávor, L., Nagy, I., Adám, I., Szirmai, I., Simó, M., Ertsey, C., I, Amrein, Kamondi, A., Harcos, P., Dobos, E., Szabó, B., Balas, V., Guseo, A., Fodor, E., Jófejü, E., Eizler, K., Csiba, L., Csépány, T., Pallagi, E., Bereczki, D., Jakab, G., Juhász, M., Bszabó, B. Szabó I. Mayer, Katona, G., Hutchinson, M., O’Dwyer, J., O’Rourke, K., Sanders, E. A. C. M., Rijk van Andel, J. F., Bomhof, M. A. M., van Erven, P., Hintzen I. Hoppenbrouwers, R. Q. Hintzen I. Hoppenbrouwers, Neuteboom, R. F., Zemel, D., van Doorn, P. A., Jacobs, B. C., Munster, E. T. h. L. Van, ter Bruggen, J. P., Bernsen, R., Jongen, P. J. H., de Smet, E. A. A., Tacken, H. F. H., Polman, C., Zwemmer, J., Nielsen, J., Kalkers, N., Kragt, J., Jasperse, B., Willoughby, E., Anderson, N. E., Barber, A., Anderson, T., Parkin, P. J., Fink, J., Avery, S., Mason, D., Kwiecinski, H., Zakrzewska Pniewska, B., Kaminska, A., Podlecka, A., Nojszewska, M., Czlonkowska, A., Zaborski, J., Wicha, W., Kruszewska Ozimowska, J., Darda Ledzion, L., Selmaj, K., Mochecka Thoelke, A., Pentela Nowicka, J., Walczak, A., Stasiolek, M., Stelmasiak, Z., Bartosik Psujek, H., Mitosek Szewczyk, K., Belniak, E., Chyrchel, U., Maciejowski, M., Strzyzewska Lubos, L., Lubos, L., Matusik, E., Maciejek, Z., Niezgodzinska Maciejek, A., Sobczynska, D., Slotala, T., Wawrzyniak, S., Kochanowicz K. Kuczynski, J. Kochanowicz K. Kuczynski, Zimnoch, R., Pryszmont, M., Drozdowski, W., Baniukiewicz, E., Kulakowska, A., Borowik, H., Lewonowska, M., Szczudlik, A., Róg, T., Gryz Kurek, E., Pankiewicz, J., Furgal, J., Kimkowicz, A., Fryze, W., Wierbicki, T., Michalak, L., Kowalewska, J., Swiatkiewicz, J., Hillert, J., Åkesson, E, Fredrikson, S., Diener, P, Olsson, T., Wallström, E., Fpiehl, F. Piehl L. Hopia, Brundin, L., Marta, M., Andersson, M., Lycke, J., Runmarker, B., Malmeström, C., Vaghfeldt, P., Skoog, B., Schluep, M., Bogousslavskyr, J., Du Pasquier, R., Achtnichts, L., Kuhle, J., Buitrago Telez, C., Schläger, R., Naegelin, Y., Eraksoy, M., Bebek, N., Akman Demir, G., Topcuoglu, B., Kurtuncu, M., Istanbul, University, Istanbul:, A. Siva, Saip, S., Altintas, A., Kiyat, A., Sharief, M., Kasti, M., Lim, E. T., Rashid, W., Silber, E., Saldanha, G., Hawkins, C., Mamutse, G., Woolmore, J., Hawkes, C., Findley, L., Dasilva, R., Gunasekara, H., Palace, J., Cader, Z., Littleton, E., Burke, G., Sharrack O. Suliman, B. Sharrack O. Suliman, Klaffke, S., Swash, M., Dhillon, H., Bates, D., Westwood, M., Nichol, P., Barnes, D., Wren, D., Stoy, N., Robertson, N., Pickersgill, T., Pearson, O., Lawthom, C., Young, C., Mills, R., Lecky, B., Ford, C., Katzman, J., Rosenberg, G., Cooper, J., Wrubel, B., Richardson, B., Lynch, S., Ridings, L., Mcvey, A., Nowack, W., Rae Grant, A., Mackin, G. A., Castaldo, J. E., Spikol, L. J., Carter, J., Wingerchuk, D., Caselli, R., Dodick, D., Scarberry, S., Bailly, R., Garnaas, K., Haake, B., Rossman, H., Belkin, M., Boudouris, W. D., Pierce, R. P., Mass, M., Yadav, V., Bourdette, D., Whitham, R. H., Heitzman, D., Martin, A., Greenfield, C. F., Agius, M., Richman, D. P., Vijayan, N., Wheelock, V. L., Reder, A., Arnason, B., Noronha, A., Balabanov, R., Ray, A., Sheremata, W., Delgado, S., Shebert, B., Maldonado, J., Bowen, J., Garden, G. A., Distad, B. J., Carrithers, M., Rizzo, M., Vollmer, T., Reiningerova, J., Guarnaccia, J., Lo, A., Richardson, G. B., Fazekas, F., Enzinger, C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, E., Egg, R., Deisenhammer, F., Decoo, : D, Lampaert, J., Bartholome, E., Bier, J., Stenager, : E., Rasmussen, M., Binzer, M., Shorsh, K., Christensen, M., Soelberg Sørensen, P., Hansen, H. J., Bech, E., Petersen, T., Kirkegaard, M., Eralinna, : J., Ruutiainen, J., Soilu Hänninen, M., Säkö, E., Laaksonen, M., Reunanen, M., Remes, A., Keskinarkaus, I., Moreau, : T., Noblet, M., Rouaud, O., Couvreur, G., Lepage, E., Drapier, S., De Burghgraeve, V., Merienne, M., Cahagne, V., Gout, O., Deschamps, R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, J., Stojkovic, T., Griffié, G., Engles, Ferriby, D., Debouverie, M., Pittion Vouyouvitch, S., Lacour, J. C., Lubetzki, C., Youssov, K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, D., Renouil Guy, N., Cesaro, P., Degos, F., Benisty, S., Rumbach, L., Decavel, P., Blanc, S., Aubertin, P., Riche, G., Brochet, B., Ouallet, J. 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W., Fernandez Fernandez, : O., León, A., Romero, F., Alonso, A., Tamayo, J., Montalban, X., Nos, C., Pelayo, R., Tellez, N., Rio, J., Tintore, M., Arbizu, T., Romero, L., Moral, E., Martinez, S., Kappos, : L., Wilmes, S., Karabudak, : R., Kurne, A., Erdem, S., Siva, A., Atamer, A., Bilgili, F., Topcular, B., Giovannoni, : G., Lava, : N., Murnane, M., Dentinger, M., Zimmerman, E., Reiss, M., Gupta, V., Scott, T., Brillman, J., Kunschner, L., Wright, D., Perel, A., Babu, A., Rivera, V., Killian, J., Hutton, G., Lai, E., Picone, M., Cadivid, D., Kamin, S., Shanawani, M., Gauthier, S., Morgan, A., Buckle, G., Margolin, D., Kwen, P. L., Garg, N., Munschauer, F., Khatri, B., Rassouli, M., Saxena, V., Ahmed, A., Turner, A., Fox, E., Couch, C., Tyler, R., Horvit, A., Fodor, P., Humphries, S., Wynn, D., Nagar, C., O’Brien, D., Allen, N., Turel, A., Friedenberg, S., Carlson, J., Hosey, J., Crayton, H., Richert, J., Tornatore, C., Sirdofsky, M., Greenstein, J., Shpigel, Y., Mandel, S., Adbelhak, T., Schmerler, M., Zadikoff, C., Rorick, M., Reed, R., Elias, S., Feit, H., Angus, E., Sripathi, N., Herbert, J., Kiprovski, K., Qu, X., Del Bene, M., Mattson, D., Hingtgen, C., Fleck, J., Horak, H., Javerbaum, J., Elmore, R., Garcia, E., Tasch, E., Gruener, G., Celesia, G., Chawla, J., Miller, A., Drexler, E., Keilson, M., Wolintz, R., Drasby, E., Muscat, P., Belden, J., Sullivan, R., Cohen, J., Stone, L., Marrie, R. A., Fox, R., Hughes, B., Babikian, P., Jacoby, M., Doro, J., Puricelli, M., Boudoris, W., Pierce, R., Eggenberger, E., Birbeck, G., Martin, J., Kaufman, D., Stuart, W., English, J. B., Stuart, D. S., Gilbert, R. W., Kaufman, M., Putman, S., Diedrich, A., Follmer, R., Pelletier, D., Waubant, E., Cree, B., Genain, C., Goodin, D., Patwa, H., Rizo, M., Kitaj, M., Blevins, J., Smith, T., Mcgee, F., Honeycutt, W., Brown, M., Isa, A., Nieves Quinones, D., Krupp, L., Smiroldo, J., Zarif, M., Perkins, C., Sumner, A., Fisher, A., Gutierrez, A., Jacoby, R., Svoboda, S., Dorn, D., Groeschel, A., Steingo, B., Kishner, R., Cohen, B., Melen, O., Simuni, T., Zee, P., Cohan, S., Yerby, M., Hendin, B., Levine, T., Tamm, H., Travis, L. H., Freedman, S. M., Tim, R., Ferrell, W., Stefoski, D., Stevens, S., Katsamakis, G., Topel, J., Ko, M., Gelber, D., Fortin, C., Green, B., Logan, W., Carpenter, D., Temple, L., Sadiq, S., Sylvester, A., Sim, G., Mihai, C., Vertino, M., Jubelt, B., Mejico, L., Riskind, P., Cabo, A., Paskavitz, J., Moonis, M., Bashir J. Brockington, K. Bashir J. Brockington, Nicholas, A., Slaughter, R., Archer S. Harik, R. Archer S. Harik, Haddad, N., Pippenger, M. A., Van den Noort, S., Thai, G., Olek, M., Demetriou, M., Shin, R., Calabresi, P., Rus, H., Bever, C., Johnson, K., Sherbert, R., Herndon, R., Uschmann, H., Chandler, A., Markowitz, C., Jacobs, D., Balcer, L., Mitchell, G., Chakravorty, S., Heyman, R., Stauber, Z., Goodman, A., Segal, B., Schwid, S., Samkoff, L., Levin, M., Jacewicz, M., Menkes, D., Pulsinelli, W., Frohman, E., Racke, M., Hawker, K., Ulrich, R., Panitch, H., Hamill, R., Tandon, R., Dulaney, E., Simnad, V., Miller, J., Wooten, G. F., Harrison, M., Doherty, M., Wundes, A., Distad, J., Kachuck, N., Berkovich, R., Burnett, M., Sahai, S., Bandari, D., Weiner, L., Storey, J. R., Beesley, B., Hart, D., Moses, H., Sriram, S., Fang, J., O’Duffy, A., Kita, M., Taylor, L., Elliott, M., Roberts, J., Jeffery, D., Maxwell, S., Lefkowitz, D., Kumar, S., Sinclair, M., Radue, E. W., de Vera, A., Bacelar, O., and Kuster, P.

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Visual analogue scale, Health Status, Population, Pain, Comorbidity, Placebo, Antibodies, law.invention, Natalizumab, Randomized controlled trial, Quality of life, Double-Blind Method, law, Internal medicine, Surveys and Questionnaires, Monoclonal, medicine, Prevalence, Humans, Longitudinal Studies, education, Humanized, education.field_of_study, Expanded Disability Status Scale, Neuroscience (all), business.industry, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Female, Patient Satisfaction, Treatment Outcome, United States, Quality of Life, Multiple sclerosis, medicine.disease, Neurology, Physical therapy, Neurology (clinical), business, medicine.drug
Abstract

Objective To report the relationship between disease activity and health-related quality of life (HRQoL) in relapsing multiple sclerosis, and the impact of natalizumab. Methods HRQoL data were available from 2,113 multiple sclerosis patients in natalizumab clinical studies. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, patients received natalizumab 300mg (n = 627) or placebo (n = 315); in the Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) study, patients received interferon beta-1a (IFN-β-1a) plus natalizumab 300mg (n = 589), or IFN-β-1a plus placebo (n = 582). The Short Form-36 (SF-36) and a subject global assessment visual analog scale were administered at baseline and weeks 24, 52, and 104. Prespecified analyses included changes from baseline to week 104 in SF-36 and visual analog scale scores. Odds ratios for clinically meaningful improvement or worsening on the SF-36 Physical Component Summary (PCS) and Mental Component Summary were calculated. Results Mean baseline SF-36 scores were significantly less than the general US population and correlated with Expanded Disability Status Scale scores, sustained disability progression, relapse number, and increased volume of brain magnetic resonance imaging lesions. Natalizumab significantly improved SF-36 PCS and Mental Component Summary scores at week 104 in AFFIRM. PCS changes were significantly improved by week 24 and at all subsequent time points. Natalizumab-treated patients in both studies were more likely to experience clinically important improvement and less likely to experience clinically important deterioration on the SF-36 PCS. The visual analog scale also showed significantly improved HRQoL with natalizumab. Interpretation HRQoL was impaired in relapsing multiple sclerosis patients, correlated with severity of disease as measured by neurological ratings or magnetic resonance imaging, and improved significantly with natalizumab. Ann Neurol 2007

Published
2007

46. The incidence and significance of anti-natalizumab antibodies. Results from the AFFIRM and SENTINEL

Author

Calabresi, Pa, Giovannoni, G, Confavreux, C, Galetta, Sl, Havrdova, E, Hutchinson, M, Kappos, L, Miller, Dh, O'Connor, Pw, Phillips, Jt, Polman, Ch, Radue, Ew, Rudick, Ra, Stuart, Wh, Lublin, Fd, Wajgt, A, Weinstock Guttman, B, Wynn, Dr, Lynn, F, Panzara, Ma, Fazekas, The following investigators participated in the SENTINEL study: F., Enzinger, * C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, * E., Egg, R., Deisenhammer, F., Lampaert, D. Decoo* J., Bier, E. Bartholome* J., Stenager, Denmark: E., Rasmussen, * M., Binzer, M., Ravnborg, M., Soelberg Sørensen, * P., Blinkenberg, M., Petersen, B., Hansen, H. J., Bech, * E., Petersen, T., Kirkegaard, M., Eralinna, J., Ruutiainen, * J., Soilu Hänninen, M., Reunanen, M., Remes, * A., Keskinarkaus, I., Moreau, T., Noblet, * M., Rouaud, O., Couvreur, G., Edan, G., Lepage, * E., Drapier, S., De Burghgraeve, V., Yaouanq, J., Gout, O., Deschamps, * R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, * J., Stojkovic, T., Griffié, G., Engles, A., Ferriby, D., Debouverie, M., Pittion Vouyouvitch, * S., Lacour, J. C., Pelletier, J., Feuillet, * L., Suchet, L., Dalecky, A., Tammam, D., Lubetzki, C., Youssov, * K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, * D., Renouil Guy, N., Cesaro, P., Degos, * F., Benisty, S., Decavel, L. Rumbach* P., Confavreux, C., Blanc, * S., Aubertin, P., Riche, G., Brochet, B., Ouallet, * J. C., Anne, O., Menck, S., Grupe, * A., Guttman, E., Lensch, E., Fucik, * E., Heitmann, S., Hartung, H. P., Schröter, * M., Kurz, F. M. W., Heidenreich, F., Trebst, * C., Pul, R., Hohlfeld, R., Krumbholz, * M., Pellkofer, H., Haas, J., Segert, * A., Meyer, R., Anagnostou, P., Kabus, C., Poehlau, D., Schneider, * K., Hoffmann, V., Zettl, U., Steinhagen, * V., Adler, S., Steinbrecher, A., Rothenfusser Körber, * E., Zellner, R., Baum, K., Günther, * A., Bläsing, H., Stoll, G., Gold, * R., Bayas, * A., Kleinschnitz, C., Limmroth, V., Katsarava, * Z., Kastrup, O., Haller, P., Stoeve, * S., Höbel, D., Oschmann, P., Voigt, * K., Burger, C. V., Karusiss, O. Abramsky* D., Achiron, A., Kishner, * I., Stern, Y., Sarove Pinhas, I., Dolev, M., Magalashvili, D., Pozzili, C., Lenzi, * D., Scontrini, A., Millefiorini, E., Buttinelli, C., Gallo, Paolo, Ranzato, * F., Tiberio, M., Perini, P., Laroni, A., Marrosu, M., Marchi, * E. Cocco P., Spinicci, G., Massole, S., Mascia, M., Floris, G., Trojano, M., Bellacosa, * A., Paolicelli, D., Bosco Zimatore, G., Simone, I. L., Giorelli, M., Di Monte, E., Mancardi, G., Pizzorno, * M., Murialdo, A., Narciso, E., Capello, A., Comi, G., Martinelli, * V., Rodegher, M., Esposito, F., Colombo, B., Rossi, P., Polman, C. H., Jasperse, * M. M. S., Zwemmer, J. N. P., Nielsen, J., Kragt, J. J., Jongen, P. J. H., De Smet, * E., Tacken, H., Frequin, S. T. F. M., Siegers, * H. P., Mauser, H. W., Fernandez Fernandez, O., León, * A., Romero, F., Alonso, A., Tamayo, J., Montalban, X., Nos, * C., Pelayo, R., Tellez, N., Rio, J., Tintore, M., Arbizu, T., Romero, * L., Moral, E., Martinez, S., Kappos, L., Achtnichts, * L., Wilmes, S., Karabudak, R., Kurne, * A., Erdem, S., Siva, A., Saip, * S., Altintas, A., Atamer, A., Eraksoy, M., Bilgili, * F., Topcular, B., Lim, G. Giovannoni* E. T., Lava, N., Murnane, * M., Dentinger, M., Zimmerman, E., Gupta, M. Reiss* V., Scott, T., Brillman, * J., Kunschner, L., Wright, D., Babu, A. Perel* A., Rivera, V., Killian, * J., Hutton, G., Lai, E., Picone, Bernard W. M., Cadivid, * D., Kamin, S., Shanawani, M., Gauthier, S., Morgan, * A., Buckle, G., Margolin, D., Weinstock Guttman, B., Kwen, * P. L., Garg, N., Munschauer, F., Khatri, B., Rassouli, * M., Saxena, V., Ahmed, A., Turner, A., Fox, E., Couch, * C., Tyler, R., Horvit, A., Humphries, P. Fodor* S., Wynn, D., Nagar, * C., O’Brien, D., Allen, N., Turel, A., Friedenberg, * S., Carlson, J., Hosey, J., Crayton, H., Richert, * J., Tornatore, C., Sirdofsky, M., Greenstein, J., Shpigel, * Y., Mandel, S., Adbelhak, T., Schmerler, M., Zadikoff, * C., Rorick, M., Reed, R., Elias, S., Feit, * H., Angus, E., Sripathi, N., Herbert, J., Kiprovski, * K., Qu, X., Del Bene, M., Mattson, D., Hingtgen, * C., Fleck, J., Horak, H., Javerbaum, J., Elmore, * R., Garcia, E., Tasch, E., Gruener, G., Celesia, * G., Chawla, J., Miller, A., Drexler, * E., Keilson, M., Wolintz, R., Drasby, E., Muscat, * P., Belden, J., Sullivan, R., Cohen, J., Stone, * L., Marrie, R. A., Fox, R., Hughes, B., Babikian, * P., Jacoby, M., Doro, J., Puricelli, M., Rossman, H., Boudoris, * W., Belkin, M., Pierce, R., Eggenberger, E., Birbeck, * G., Martin, J., Kaufman, D., Stuart, W., English, * J. B., Stuart, D. S., Gilbert, R. W., Kaufman, MS M., Putman, . *. S., Diedrich, A., Follmer, R., Pelletier, D., Waubant, * E., Cree, B., Genain, C., Goodin, D., Guarnaccia, J., Patwa, * H., Rizo, M., Kitaj, M., Blevins, Neurolo J., Smith, * T., Mcgee, F., Honeycutt, W., Brown, * M., Isa, A., Nieves Quinones, D., Krupp, L., Smiroldo, * J., Zarif, M., Perkins, C., Sumner, A., Fisher, A., Gutierrez, A., Jacoby, R., Svoboda, * S., Dorn, D., Groeschel, A., Kishner, B. Steingo* R., Cohen, B., Melen, * O., Simuni, T., Zee, P., Yerby, S. Cohan* M., Hendin, B., Levine, * T., Tamm, H., Travis, L. H., Freedman, S. M., Tim, * R., Ferrell, W., Stefoski, D., Stevens, * S., Katsamakis, G., Topel, J., Ko, M., Fortin, D. Gelber* C., Green, B., Logan, * W., Carpenter, D., Temple, L., Sadiq, S., Sylvester, * A., Sim, G., Mihai, C., Vertino, * M., Jubelt, B., Mejico, L., Phillips, J. T., Martin, * A., Heitzman, D., Greenfield, C. F., Riskind, P., Cabo, * A., Paskavitz, J., Moonis, M., Bashir, K., Brockington, * J., Nicholas, A., Slaughter, R., Archer, R., Harik, * S., Haddad, N., Pippenger, M. A., Van den Noort, S., Thai, * G., Olek, M., Demetriou, M., Shin, R., Cala bresi, * P., Rus, H., Bever, C., Johnson, K., Sheremata, W., Delgado, * S., Sherbert, R., Herndon, R., Uschmann, * H., Chandler, A., Markowitz, C., Jacobs, * D., Balcer, L., Mitchell, G., Chakra vorty, * S., Heyman, R., Stauber, Z., Goodman, A., Segal, * B., Schwid, S., Samkoff, L., Levin, M., Jacewicz, * M., Menkes, D., Pulsinelli, W., Frohman, E., Racke, * M., Hawker, K., Ulrich, R., Panitch, H., Hamill, * R., Tandon, R., Dulaney, E., Simnad, V., Miller, * J., Wooten, G. F., Harrison, M., Bowen, J., Doherty, * M., Wundes, A., Garden, G. A., Distad, J., Kachuck, N., Berkovich, * R., Burnett, M., Sahai, S., Bandari, D., Weiner, L., Storey, J. R., Beesley, * B., Hart, D., Moses, H., Sriram, * S., Fang, J., O’Duffy, A., Kita, M., Taylor, * L., Elliott, M., Roberts, J., Jeffery, D., Maxwell, * S., Lefkowitz, D., Kumar, S., and Sinclair, M.

Published
2007

47. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis

Author

Richard, A. Rudick, William, H. Stuart, Peter, A. Calabresi, Christian, Confavreux, Steven, L. Galetta, Ernst Wilhelm, Radue, Fred, D. Lublin, Bianca, Weinstock Guttman, Daniel, R. Wynn, Frances, Lynn, Msc, M. S. c., Michael, A. Panzara, Alfred, W. Sandrock, For, the SENTINEL Investigators including: F. Fazekas, Enzinger, C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, E., Egg, R., Eisenhammer, F., Decoo J. Lampaert, D. Decoo J. Lampaert, Bartholome J. Bier, E. Bartholome J. Bier, Stenager, E., Rasmussen, M., Binzer, M., Shorsh, K., Christensen, M., Ravnborg, M., Soelberg Sørensen, P., Blinkenberg, M., Petersen, B., Hansen, H. J., Bech, E., Petersen, T., Kirkegaard, M., Eralinna, J., Ruutiainen, J., Soilu Hänninen, M., Säkö, E., Laaksonen, M., Reunanen, M., Remes, A., Keskinarkaus, I., Moreau, T., Noblet, M., Rouaud, O., Couvreur, G., Edan, G., Lepage, E., Drapier, S., De Burghgraeve, V., Yaouanq, J., Merienne, M., Cahagne, V., Gout, O., Deschamps, R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, J., Stojkovic, T., Griffié, G., Engles, A., Ferriby, D., Debouverie, M., Pittionvouyouvitch, S., Lacour, J. C., Pelletier, J., Feuillet, L., Suchet, L., Dalecky, A., Tammam, D., Lubetzki, C., Youssov, K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, D., Renouil Guy, N., Cesaro, P., Degos, F., Benisty, S., Rumbach P. Decavel, L. Rumbach P. Decavel, Confavreux, C., Blanc, S., Aubertin, P., Riche, G., Brochet, B., Ouallet, J. C., Anne, O., Menck, S., Grupe, A., Guttman, E., Lensch, E., Fucik, E., Heitmann, S., Hartung, H. P., Schröter, M., Kurz, F. M. 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Subjects
Adult, Male, Infusions, medicine.medical_specialty, Multiple Sclerosis, Adolescent, Combination therapy, Integrin alpha4, Peripheral edema, Progressive Multifocal, Relapsing-Remitting, Gastroenterology, Antibodies, Natalizumab, Drug Therapy, Leukoencephalopathy, Internal medicine, Monoclonal, Secondary Prevention, medicine, Humans, Humanized, Proportional Hazards Models, Expanded Disability Status Scale, business.industry, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Brain, Cell Adhesion Molecules, Disease Progression, Drug Therapy, Combination, Female, Infusions, Intravenous, Interferon-beta, JC Virus, Leukoencephalopathy, Progressive Multifocal, Middle Aged, Multiple Sclerosis, Relapsing-Remitting, Medicine (all), Progressive multifocal leukoencephalopathy, Multiple sclerosis, Hazard ratio, Interferon beta-1a, General Medicine, medicine.disease, Surgery, Combination, medicine.symptom, Intravenous, business, medicine.drug
Abstract

Background Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an α 4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies. Methods We randomly assigned 1171 patients who, despite interferon beta-1a therapy, had had at least one relapse during the 12-month period before randomization to receive continued interferon beta-1a in combination with 300 mg of natalizumab (589 patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks. The primary end points were the rate of clinical relapse at 1 year and the cumulative probability of disability progression sustained for 12 weeks, as measured by the Expanded Disability Status Scale, at 2 years. Results Combination therapy resulted in a 24 percent reduction in the relative risk of sustained disability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Kaplan–Meier estimates of the cumulative probability of progression at two years were 23 percent with combination therapy and 29 percent with interferon beta-1a alone. Combination therapy was associated with a lower annualized rate of relapse over a two-year period than was interferon beta-1a alone (0.34 vs. 0.75, P

Published
2006

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