title: Factors associated with clinically significant increased walking time in multiple sclerosis: results of a survival analysis of short-term follow-up data from a clinical database.
abstract: BACKGROUND
  Because multiple sclerosis (MS) is variable and unpredictable, if symptom worsening could be predicted, patients may feel better prepared to manage changes in function.
  
  
  OBJECTIVE
  The objective of this paper is to study the prediction of walking impairment in MS.
  
  
  METHODS
  We retrieved data for all MS patients at our center (2008-2009), including baseline and follow-up timed 25-foot walk (T25FW) times. We assessed the incidence of ≥20% worsening in T25FW by developing two survival models: (1) disease course and (2) Multiple Sclerosis Performance Scales (MSPS) score. The outcome was days until ≥20% worsening in T25FW. Covariates were disease subtype, years since diagnosis, Patient Health Questionnaire-9 (PHQ-9) score, and demographics. Data were interval censored; missing data were handled with multiple imputation.
  
  
  RESULTS
  Of 1544 patients, 309 (20%) experienced ≥20% worsening T25FW. For disease course, time to worsening was significantly shorter for secondary progressive vs. relapsing-remitting disease (p < 0.001). For MSPS, patients with lower baseline MSPS scores progressed more slowly (p = 0.001). In both models, sex, baseline T25W, and time since diagnosis were significantly associated with worsening. In the disease course model, PHQ 9 score may be related to worsening (p = 0.07).
  
  
  CONCLUSIONS
  These findings suggest factors associated with worsening in T25FW and a potential approach to establishing indicators associated with clinically significant change.
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, USA millerd@ccf.org.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Miller
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research/Neurological Institute Center for Outcomes Research and Evaluation/ Department of Quantitative Health Sciences, Cleveland Clinic, USA.
authors.forename: Nicolas R
authors.initials: NR
authors.lastname: Thompson
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Cohen
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fox
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, USA.
authors.forename: Jen
authors.initials: J
authors.lastname: Hartman
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Schwetz
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, USA.
authors.forename: Devon S
authors.initials: DS
authors.lastname: Conway
authors.affiliation: Biogen Idec./Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rudick
mesh_terms: D000328:Adult; D016208:Databases, Factual; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications*; D016138:Walking
keywords: Multiple sclerosis; accelerated failure time; disease progression; electronic health record; survival analysis; timed 25-foot walk test