R Tortelli1, M Copetti2, F Panza1,3,4, A Fontana2, R Cortese3, R Capozzo1, A Introna3, E D'Errico3, S Zoccolella3, S Arcuti1, D Seripa4, I L Simone3, G Logroscino1,3. 1. Unit of Neurodegenerative Diseases, Department of Clinical Research in Neurology, University of Bari 'Aldo Moro', Tricase, Lecce, Italy. 2. Unit of Biostatistics, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy. 3. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy. 4. Geriatric Unit and Laboratory of Gerontology and Geriatrics, Department of Medical Sciences, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
Abstract
BACKGROUND AND PURPOSE: A strong association between time to generalization (TTG), considered as the time of spreading of the clinical signs from spinal or bulbar localization to both, and survival was recently identified in patients with amyotrophic lateral sclerosis (ALS). Thus, TTG may be used as an early to intermediate end-point in survival studies. The aim of the present study was to test TTG as a predictor of survival in ALS. METHODS: This was an observational retrospective study of ALS patients from a tertiary referral centre over a 5-year follow-up period. RESULTS: In 212 ALS patients, TTG was associated with time to death/tracheostomy [R 0.62, 95% confidence interval (CI) 0.53-0.70; P < 0.001]. In a time-to-event analysis, longer TTG resulted in lower risk to reach a composite outcome (death or tracheostomy) both in univariate [hazard ratio (HR) 0.98, 95% CI 0.97-0.99] and multivariate Cox analyses (HR 0.98, 95% CI 0.96-0.99). TTG predicted death/tracheostomy at 4 years (C-statistic 0.58; 95% CI 0.53-0.63) and at 5 years (C-statistic 0.58; 95% CI 0.53-0.62). CONCLUSIONS: Based on the present results from a large clinical cohort, TTG may be used as a new early to intermediate end-point to describe the ALS natural history. TTG may be potentially useful as a new primary outcome measure for clinical trials.
BACKGROUND AND PURPOSE: A strong association between time to generalization (TTG), considered as the time of spreading of the clinical signs from spinal or bulbar localization to both, and survival was recently identified in patients with amyotrophic lateral sclerosis (ALS). Thus, TTG may be used as an early to intermediate end-point in survival studies. The aim of the present study was to test TTG as a predictor of survival in ALS. METHODS: This was an observational retrospective study of ALSpatients from a tertiary referral centre over a 5-year follow-up period. RESULTS: In 212 ALSpatients, TTG was associated with time to death/tracheostomy [R 0.62, 95% confidence interval (CI) 0.53-0.70; P < 0.001]. In a time-to-event analysis, longer TTG resulted in lower risk to reach a composite outcome (death or tracheostomy) both in univariate [hazard ratio (HR) 0.98, 95% CI 0.97-0.99] and multivariate Cox analyses (HR 0.98, 95% CI 0.96-0.99). TTG predicted death/tracheostomy at 4 years (C-statistic 0.58; 95% CI 0.53-0.63) and at 5 years (C-statistic 0.58; 95% CI 0.53-0.62). CONCLUSIONS: Based on the present results from a large clinical cohort, TTG may be used as a new early to intermediate end-point to describe the ALS natural history. TTG may be potentially useful as a new primary outcome measure for clinical trials.
Authors: Rosa Capozzo; Celeste Sassi; Monia B Hammer; Simona Arcuti; Chiara Zecca; Maria R Barulli; Rosanna Tortelli; J Raphael Gibbs; Cynthia Crews; Davide Seripa; Francesco Carnicella; Claudia Dell'Aquila; Marco Rossi; Filippo Tamma; Francesco Valluzzi; Bruno Brancasi; Francesco Panza; Andrew B Singleton; Giancarlo Logroscino Journal: Alzheimers Dement Date: 2017-03-03 Impact factor: 21.566
Authors: Rosanna Tortelli; Chiara Zecca; Marco Piccininni; Sara Benmahamed; Maria Teresa Dell'Abate; Maria Rosaria Barulli; Rosa Capozzo; Petronilla Battista; Giancarlo Logroscino Journal: Front Neurol Date: 2020-11-13 Impact factor: 4.003