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Physician referral improves adherence to the physical activity guidelines for adults with MS: A randomized controlled trial

Published:October 22, 2019DOI:https://doi.org/10.1016/j.msard.2019.101441

      Highlights

      • Physician referral enhances adherence to physical activity.
      • Higher exercise self-efficacy is associated with higher physical activity adherence.
      • Baseline fitness, function or EDSS score did not affect physical activity adherence.

      Abstract

      Background

      Commitment and adherence to community-based physical activity can be a challenge for clinical populations. The aim of this study was to explore the effectiveness of physician referral on adherence to the Physical Activity Guidelines (PAGs) for adults with MS.

      Methods

      Ninety-one participants with MS (age: 47.9 ± 10.4 years, EDSS score: 3.5 ± 1.8) were randomized into a direct referral to PAGs from a physician (REF) or control (CON) group (given a print copy of PAGs). After 16 weeks participants were categorized as either PAG “Adherers” (n = =30) or “Non-Adherers” (n = =49), based on achieving an adherence rate of ≥ 75%.

      Results

      Adherence to the PAGs was significantly higher in REF (68.0 ± 28.6%) compared with CON (35.1 ± 35.0%) (p < 0.05). There were no differences in EDSS scores, time since diagnosis, fitness, fatigue, mobility or QOL between those who adhered or did not adhere to the PAGs (p > 0.05), but greater self-efficacy for exercise at baseline was associated with higher adherence (p < 0.0001).

      Interpretation

      Direct referral to physical activity from a physician is twice as effective as simply providing information about physical activity for adherence to the PAG in people with MS. As physical activity is recognized as an effective therapeutic option for adults with MS it is important that physicians play a role in prescribing it to their patients.

      Trial registration

      ClinicalTrials.gov Identifier: NCT02100020

      Keywords

      1. Introduction

      Physical activity is a powerful tool that can be utilized in the Multiple Sclerosis (MS) population for symptom management through modifying fitness, fatigue, mobility, depression and pain (
      • Latimer-Cheung A.E.
      • Pilutti L.A.
      • Hicks A.L.
      • et al.
      Effects of exercise training on fitness, mobility, fatigue, and health-related quality of life among adults with multiple sclerosis: a systematic review to inform guideline development.
      ). Despite these benefits, at least two-thirds of people living with MS do not participate in regular physical activity (
      • Motl R.W.
      • McAuley E.
      • Snook E.M.
      Physical activity and multiple sclerosis: a meta-analysis.
      ). Commitment and adherence to community-based physical activity can be a challenge for people living with MS as they have to overcome numerous barriers on a daily basis (with respect to disease symptoms, transportation issues, fatigue) (
      • Becker H.
      • Stuifbergen A.
      What makes it so hard? Barriers to health promotion experienced by people with multiple sclerosis and polio.
      ). In other clinical populations (e.g. cardiac patients), there is evidence to suggest that direct referral to community-based exercise from a physician can be a strong predictor for physical activity adherence (
      • Jackson L.
      • Leclerc J.
      • Erskine Y.
      • Linden W.
      Getting the most out of cardiac rehabilitation: a review of referral and adherence predictors.
      ;
      • Dunn S.L.
      • Dunn L.M.
      • Buursma M.P.
      • et al.
      Home- and Hospital- Based Cardiac rehabilitation exercise: the important role of physician recommendation.
      ). Therefore, there is potential for physical activity participation rates in the MS population to improve if physicians took a more active role in referring their patients to appropriate physical activity programs.
      Characterizing or defining what constitutes physical activity adherence across exercise studies is variable, although most studies calculate adherence rates as the number of sessions attended over the total number of sessions for the duration of the study (
      • Heesen C.
      • Bruce J.
      • Gearing R.
      • et al.
      Adherence to behavioural interventions in multiple sclerosis: follow-up meeting report ([email protected]).
      ). Currently there is no gold standard defining what constitutes physical activity adherence, nor do we know the number of training sessions required to incur significant benefits from physical activity. Studies evaluating adherence to physical activity in other populations have defined successful adherence as attending between 66–100% (x¯ = 75%) of prescribed sessions (
      • Deka P.
      • Pozehl B.
      • Williams M.A.
      • Yates B.
      Adherence to recommended exercise guidelines in patients with heart failure.
      ;
      • Geraedts H.A.E.
      • Zijlstra W.
      • Zhang W.
      • Bulstra S.
      • Stevens M.
      Adherence to and effectiveness of an individually tailored home-based exercise program for frail older adults, driven by mobility monitoring: design of a prospective cohort study.
      ;
      • Hicks G.
      • Benvenuti F.
      • Fiaschi V.
      • et al.
      Adherence to a community-based exercise program is a strong predictor of improved back pain status in older adults: an observational study.
      ;
      • Kampshoff C.S.
      • Van Mechelen W.
      • Schep G.
      • et al.
      Participation in and adherence to physical exercise after completion of primary cancer treatment.
      ;
      • Kronish I.M.
      • Diaz K.M.
      • Goldsmith J.
      • Moise N.
      • Schwartz J.E.
      Objectively measured adherence to physical activity guidelines after acute coronary syndrome.
      ;
      • Shumway-cook A.
      • Silver I.F.
      • LeMier M.
      • York S.
      • Cummings P.
      • Koepsell T.D.
      Effectiveness of a community-based multifactorial intervention on falls and fall risk factors in controlled trial.
      ;
      • Sjosten N.M.
      • Salonoja M.
      • Piirtola M.
      • et al.
      A multifactorial fall prevention programme in the community-dwelling aged: predictors of adherence.
      ); this average of 75% was used to define adherence in the current study.
      In 2012, the first evidence-informed physical activity guidelines (PAGs) specific to the MS population were released to the general public (

      mssociety.ca. [Internet]. Toronto: multiple sclerosis society of Canada; c2018 [cited2018Aug 10]. Available from: https://mssociety.ca/support-services/programs-and-services/recreation-and-social-programs/physical-activity/the-guidelines.

      ). These guidelines provide minimum thresholds of aerobic and strength exercises that are predicted to induce improvements in both fitness and function in adults with MS, and the effectiveness of the PAGs has recently been published
      • Canning K.L.
      • Hicks A.L.
      Benefits of adhering to the physical activity guidelines for adults with MS go beyond aerobic fitness and strength.
      . The objectives of this study were to determine the effect of direct physician referral on adherence to the PAGs for people living with MS in a community setting and to identify what other factors may also be related to PAG adherence.

      2. Methods

      2.1 Participants

      Detailed recruitment and enrollment information is provided in the flow diagram (Fig. 1). Ninety-one participants with diagnosis of MS volunteered to participate in a 16wk randomized controlled trial (RCT) at McMaster University in Hamilton, ON from July 2014 - March 2017. Inclusion criteria consisted of; i) EDSS score between 1 and 7, ii) aged 18 to 64 years and iii) medical clearance to participate in exercise. Exclusion criteria included; i) current participation in physical activity (≥ twice weekly) and ii) other serious medical condition that would impair ability to participate in strength or aerobic training. All participants provided written informed consent and all procedures were approved and conducted in accordance with the ethical guidelines of the Hamilton Integrated Research Ethics Board. Participants were randomized to a direct referral group (REF) or a control group (CON) after baseline testing was completed and randomization allocation was blinded to testers. Participants randomized to the REF group received a written prescription for exercise by a physician based on the PAG recommendations and referred to a community-based exercise program at McMaster University. Participants randomized to the CON group were given a print copy of the PAGs and an online link for information about physical activity and MS. CON participants had to use their own initiative to seek out community based exercise opportunities. Twelve participants (4 from REF, 8 from CON) were lost to follow-up; statistics were performed on the 79 participants who completed follow-up testing after the 16 week study period.
      Fig. 1
      Fig. 1CONSORT Flow diagram of participant recruitment and enrollment.

      2.2 Physician referral

      The physician referral form was filled out by the lead Neurologist at Hamilton Health Science's MS Clinic. The referral form replicated a physicians’ prescription pad wherein participants were prescribed exercise in accordance with the PAGs for adults living with MS (

      Canadian Society for Exercise Physiology. Physical activity guidelines for adults with ms. http://www.csep.ca/en/guidelines/physical-activity-guidelines-for-special-populations (2012, accessed 27 March 2018).

      ). The form also included a referral to an appropriate exercise program at McMaster University. Participants who joined the exercise program participated in supervised, twice-weekly exercise sessions that involved both aerobic and resistance exercise. Each participant worked one-on-one with an exercise trainer who monitored each exercise session, recorded the details pertaining to all exercises completed and progressed the intensity of the prescription as appropriate. The membership fee for this program ($55/month + $20/month parking if required) was the responsibility of the study participant.

      2.3 Demographics and questionnaires

      Participants completed a variety of questionnaires assessing demographics, quality of life (QOL), fatigue symptoms and self-efficacy for exercise at baseline and post-testing. QOL was assessed using the MS Quality of Life 54 (MSQOL-54) (
      • Vickrey B.G.
      • Hays R.D.
      • Harooni R.
      • et al.
      A health-related quality of life measure for multiple sclerosis.
      ), and fatigue was assessed using the Modified Fatigue Impact Scale (MFIS-5) (
      • Fisk J.D.
      • Ritvo P.G.
      • Ross L.
      • et al.
      Measuring the functional impact of fatigue : initial validation of the fatigue impact scale.
      ). A questionnaire previously used in the spinal cord injury population was used to determine self-efficacy for exercise (
      • Latimer A.E.
      • Ginis K.A.M.
      • Arbour K.P.
      The efficacy of an implementation intention intervention for promoting physical activity among individuals with spinal cord injury : a randomized controlled trial.
      ). Questionnaire items included items assessing participants’ perceptions of the value of the PAGs, expectations about the benefits of meeting the guidelines and confidence to engage in the recommended amount of physical activity. The questionnaire assessed participants’ confidence and intentions to follow the PAGs, addressing both the aerobic and muscle strengthening portions of the guidelines separately (
      • Latimer A.E.
      • Ginis K.A.M.
      • Arbour K.P.
      The efficacy of an implementation intention intervention for promoting physical activity among individuals with spinal cord injury : a randomized controlled trial.
      ). All self-efficacy items were rated on a 7 point Likert scale from 1 (strongly disagree/not at all confident) to 7 (strongly agree/completely confident). One total score was reported for outcome expectation and 4 total scores were reported for self-efficacy beliefs regarding strengthening and aerobic exercise.

      2.4 Peak aerobic capacity

      To measure peak oxygen consumption, a progressive VO2 peak test to peak oxygen consumption or volitional exhaustion on an arm cycle ergometer (Lode B.V., Groningen, Netherlands) was completed by participants. The resistance started at 0 W and increased thereafter by 10 W every minute and participants were asked to keep their RPMs between 50–60 RPM. Heart rate (Polar Electro, Lachine, QC, Canada) and VO2 (Moxus Metabolic System, AEI Technologies, Pittsburgh, PA, USA) were continuously measured. The test was terminated if a) the participant reached volitional exhaustion, b) the cycling rate dropped below 50 RPM c) a plateau in VO2 was observed, or d) heart rate was greater than 90% of the participants’ age predicted maximum heart rate.

      2.5 Muscle strength

      One repetition maximum (1RM) strength testing using established procedures (
      • Kraemer W.
      • Ratamess N.
      • Fry A.
      • French D.
      Strength training: development and evaluation of methodology.
      ) was completed on a multi-station (wheelchair accessible) weight training system (Equalizer Multi-Station, Equalizer Exercise Machines, Red Deer, AB, Canada), unilateral wall pulleys (Endorphin Pulleys, Patterson Medical Supply, Mississauga, ON, Canada) and using the HUR leg extension/flexion machine (HUR Health & Fitness Canada INC, Canada). 1RM was assessed in the back, chest, biceps, triceps, shoulder flexors, shoulder extensors, hamstrings and quadriceps muscles and a composite strength score was calculated.

      2.6 Mobility

      Mobility was assessed using established procedures for the 25 ft walk test (
      • Fischer J.S.
      • Jak A.J.
      • Knicker J.E.
      • Rudick R.A.
      • Cutter G.R.
      Administration and Scoring Manual For the Multiple Sclerosis Functional Composite Measure (MSFC).
      ). Participants were instructed to walk 25 ft as quickly as possible but safely and in their usual manner and they repeated this twice. An average of the 2 attempts was calculated.

      2.7 Adherence to PAGs

      Adherence was assessed over 16 weeks by weekly physical activity logs. Participants were emailed weekly logs for aerobic and strengthening exercises completed. If participants were unable to access internet, paper copies of 16 weeks of logs were provided at baseline testing and participants were instructed to return the physical activity logs at post-testing. Detailed information about type, duration and intensity of exercise was provided by participants in the logs for analysis of adherence. Adherence to the PAGs was calculated as the number of weeks (calculated as a percentage) participants achieved both the aerobic and resistance exercise recommendations over the 16 week period. At the end of the study, participants were classified as an “Adherer” if they met the PAGs recommendations for 12 out of 16 weeks, or had a calculated adherence rate of 75%.

      2.8 Data analyses

      Continuous variables are reported as means and standard deviations and categorical variables are presented as frequencies and prevalence values. Differences in baseline values were compared between randomized groups using independent samples t-tests. Differences in baseline values between Adherers and Non-Adherers were compared post-hoc using independent samples t-tests. Stepwise multiple regression analyses were used to determine what factors predict adherence. Pearson R correlational analyses were used to assess relationships between outcome variables and adherence. All statistical analyses were performed using IBM SPSS Statistics v24. Statistical significance was set at alpha < 0.05.

      3. Results

      3.1 Participant characteristics

      Seventy-nine participants (age 47.9 ± 10.0 years, EDSS score 3.5 ± 1.8, 12.1 ± 10.0 years living with MS) completed follow-up; 42 had been randomized into the REF group and 37 were randomized into the CON group. Demographic characteristics are presented in Table 1; there were no significant differences between groups. The study sample had a wide range in baseline characteristics; age (range: 22–64 years), EDSS score (range: 1–7), time since diagnosis (range: 1 month-39 years), fatigue scores (range: 2–20) and mobility (range: 0.08–2.25 m/s).
      Table 1Participant characteristics.
      CharacteristicMean ± SD
      REF (n == 42)CON (n == 37)
      Age (y)46.8 ± 10.548.9 ± 10.3
      Female (N,%)26 (63)22 (63)
      EDSS3.5 ± 1.83.5 ± 1.8
      Time Since Diagnosis (y)10.9 ± 8.913.8 ± 11.1
      RRMS (N,%)27 (66)23 (59)
      REF, Referral Group.
      CON, Control Group.
      EDSS, Expanded Disability Status Score.
      RRMS, Relapse-Remitting MS.

      3.2 Adherence

      All participants who participated in follow-up testing successfully completed the weekly physical activity logs. The effect of direct referral on adherence is displayed in Fig. 2. Over the 16-wk study period, participants in the REF group had twice the adherence rate to the PAGs as those in the CON group (p < 0.05; 68.0 ± 28.6%, range: 0–100% versus 35.1 ± 35.0%, range: 0–100%). Thirty-seven people in the REF group joined either the community-based exercise program at McMaster University or another fitness center whereas only 15 people in the CON group joined a community-based program. Within each group there was a wide range of adherence to the PAGs (0–100%); 30 participants were subsequently classified as Adherers (22 from REF, 8 from CON) and 49 were classified as Non-Adherers (20 from REF, 29 from CON) (
      • Canning K.L.
      • Hicks A.L.
      Benefits of adhering to the physical activity guidelines for adults with MS go beyond aerobic fitness and strength.
      ). Participants who adhered to the PAGs over the 16 week study period significantly improved aerobic fitness, strength in major muscle groups, mobility, fatigue symptoms and overall health-related QOL (
      • Canning K.L.
      • Hicks A.L.
      Does following the physical activity guidelines for people with multiple sclerosis result in improved fitness and function?.
      ;
      • Canning K.L.
      • Hicks A.L.
      Benefits of adhering to the physical activity guidelines for adults with MS go beyond aerobic fitness and strength.
      ).
      Fig. 2
      Fig. 2The effect of direct referral on adherence.
      * significant difference (p < 0.05).

      3.3 Baseline characteristics in adherers and non-adherers

      There were no significant differences in demographics, fitness or functional outcomes at baseline between those who adhered or did not adhere to the PAGs (p > 0.05; Table 2). No significant correlations were observed between any of the baseline demographic, fitness or functional outcomes and adherence (p > 0.05).
      Table 2Baseline demographic, fitness & functional characteristics of adherers and non-adherers.
      CharacteristicMean ± SDp Value
      Adherers (n == 30)Non-Adherers (n == 49)
      Age (y)49.7 ± 8.146.6 ± 11.4p == 0.179
      EDSS3.6 ± 1.73.5 ± 1.9p == 0.781
      Time Since Diagnosis (y)12.6 ± 8.112.0 ± 11.1p == 0.816
      VO2 Peak (ml/kg/min)13.8 ± 5.614.1 ± 4.2p == 0.783
      Composite Strength (1RM, kg)16.4 ± 5.017.0 ± 5.7p == 0.626
      25FTW Speed (m/s)1.4 ± 0.51.2 ± 0.5p == 0.258
      MFIS-511.0 ± 4.511.0 ± 3.3p == 0.964
      Physical Health QOL53.5 ± 17.851.8 ± 16.7p == 0.320
      Mental Health QOL68.2 ± 15.361.5 ± 21.3p == 0.681
      EDSS, Expanded Disability Status Score.
      1RM, One Repetition Maximum.
      25FTW, 25 Foot Walk Test.
      MFIS-5, 5 item Modified Fatigue Impact Scale.
      QOL, Quality of Life.

      3.4 Self-Efficacy

      Table 3 indicates that participants classified as Adherers had greater self-efficacy for exercise at baseline compared to the Non-Adherers (p < 0.0001). Significant moderate correlations were observed between baseline self-efficacy scores for meeting the aerobic and strengthening portions of the PAGs and adherence (r == 0.473, p < 0.0001; r == 0.484, p < 0.0001, respectively). Higher self-efficacy scores at baseline were associated with greater adherence to the PAGs.
      Table 3Baseline self-efficacy for exercise constructs of adherers and non-adherers.
      CharacteristicMean ± SDpvalue
      Adherers (n == 30)Non-Adherers (n == 49)
      Total Score 164.5 ± 7.360.6 ± 8.4p == 0.078
      Total Score 227.5 ± 1.624.0 ± 4.6p < 0.0001
      Total Score 313.7 ± 0.811.6 ± 2.4p < 0.0001
      Total Score 427.2 ± 2.122.9 ± 5.9p < 0.0001
      Total Score 534.1 ± 2.328.8 ± 6.7p < 0.0001
      Total Score 1, Overall Outcome Expectations.
      Total Score 2, Self-Efficacy Beliefs for Completing Aerobic Exercise at Targeted Intensities & Durations.
      Total Score 3, Self-Efficacy Beliefs for Completing Aerobic Exercise Sessions.
      Total Score 4, Self-Efficacy Beliefs for Completing Resistance Exercise.
      Total Score 5, Self-Efficacy Beliefs for Completing Exercise Program Over Time.

      3.5 Significant predictors for adherence

      From the step-wise regression analysis, Group (REF v. CON) and self-efficacy for completing the aerobic component of the PAGs significantly predicted adherence, accounting for 33% of variance in the model (R == 0.57, R2== 0.33, p < 0.05).

      4. Discussion

      As physical activity is recognized as an effective therapeutic option to both manage symptoms and improve fitness and function in people living with MS, it is important to identify factors that could improve physical activity adherence in this population. The objective of this study was to determine the effect of physician referral on adherence to the PAGs in people with MS, and to identify other factors that may also predict PAG adherence. The findings suggest that physician referral to an exercise program is twice as effective as simply providing written information about the PAGs to adults living with MS. Further, we found that baseline self-efficacy for exercise is an additional predictor of adherence to the PAGs in this population. These results have clear implications for the important role physicians can play in promoting physical activity to their patients with MS.
      Patients with MS identify physicians and allied healthcare professionals as the most credible source for physical activity information (
      • Heesen C.
      • Bruce J.
      • Gearing R.
      • et al.
      Adherence to behavioural interventions in multiple sclerosis: follow-up meeting report ([email protected]).
      ), and the results from this RCT certainly support this observation. Our results highlight the importance of physician referral in improving physical activity adherence, and align with what has been observed in the cardiac rehabilitation setting (
      • Jackson L.
      • Leclerc J.
      • Erskine Y.
      • Linden W.
      Getting the most out of cardiac rehabilitation: a review of referral and adherence predictors.
      ;
      • Dunn S.L.
      • Dunn L.M.
      • Buursma M.P.
      • et al.
      Home- and Hospital- Based Cardiac rehabilitation exercise: the important role of physician recommendation.
      ). Having disease specific PAGs (

      Canadian Society for Exercise Physiology. Physical activity guidelines for adults with ms. http://www.csep.ca/en/guidelines/physical-activity-guidelines-for-special-populations (2012, accessed 27 March 2018).

      ) should make it much easier for physicians to talk about the importance of physical activity to their patients and to make baseline recommendations for the types, intensities and amounts of physical activity they should engage in.
      One of the more interesting results from this current study was that there were no differences in EDSS score, time since diagnosis, fitness parameters, fatigue symptoms or overall health-related QOL between participants who ended up adhering or not adhering to the PAGs. The observation that MS-related symptoms do not seem to predict adherence to physical activity is noteworthy. There is evidence that individuals with MS who reported a greater number of symptoms during the past 30 days engaged in lower amounts of physical activity (
      • Motl R.W.
      • Snook E.M.
      • Mcauley E.
      • Gliottoni R.C.
      Symptoms, self-efficacy, and physical activity among individuals with multiple sclerosis.
      ), but the results from this study suggest that physician referral might override any potential negative effect of symptomology on the decision to participate in physical activity. It is also important to highlight that participants in the current study had to take the initiative to join (and pay for) the exercise program, enhancing its ecological validity.
      Apart from physician referral, a higher self-efficacy for exercise was the only additional predictor of PAG adherence in this randomized, community-based sample of adults living with MS. Social Cognitive Theory is a theoretical framework that describes behaviour by personal self-control and can be used to identify constructs (e.g. self-efficacy and outcome expectations) as targets for changing health behaviours (i.e. physical activity) (
      • Bandura A.
      Health promotion by social cognitive means.
      ). Research by Motl and colleagues has shown that these constructs from Social Cognitive Theory determine physical activity behaviour in adults with MS (
      • Motl R.W.
      • McAuley E.
      • Sandroff B.M.
      Longitudinal change in physical activity and its correlates in relapsing-remitting multiple sclerosis.
      ;
      • Suh Y.
      • Weikert M.
      • Dlugonski D.
      • Balantrapu S.
      • Motl R.W.
      Social cognitive variables as correlates of physical activity in persons with multiple sclerosis: findings from a longitudinal, observational study.
      ). Previous cross-sectional studies in the MS population have revealed self-efficacy for exercise to be a strong predictor of adherence to physical activity (
      • Kayes N.M.
      • McPherson K.M.
      • Schluter P.
      • Taylor D.
      • Leete M.
      • Kolt G.S.
      Exploring the facilitators and barriers to engagement in physical activity for people with multiple sclerosis.
      ;
      • Nickel D.
      • Spink K.
      • Andersen M.
      • Knox K.
      Attributions and self-efficacy for physical activity in multiple sclerosis.
      ;
      • Plow M.A.
      • Resnik L.
      • Allen S.M.
      Exploring physical activity behaviour of persons with multiple sclerosis: a qualitative pilot study.
      ); we have now validated this association in this prospective study.

      4.1 Limitations

      This study included a wide range of individuals with MS, with varying types of MS, disability levels and times since diagnosis. This could be considered both a strength and a limitation, as we may have been able to identify additional factors that predicted PA adherence if our sample was more homogeneous. The fact that we had no published guideline from which to classify “adherence” was another potential limitation, but we chose to use the average percentage of sessions attended from existing studies in the literature (75%) to use as our benchmark. Finally, reliance on physical activity logs to assess PAG adherence could have resulted in inaccurate reporting, but care was taken to fully explain how to identify various types of physical activities (and their intensities) to each participant prior to study onset, and participants were extremely compliant in filling out their weekly logs.

      5. Conclusions

      Adherence to the PAGs for people living with MS is twice as high in people who receive a direct referral from a physician. Further, baseline self-efficacy for exercise is an additional predictor. Given the multiple benefits associated with regular physical activity, and the fact that there now are evidence-based PAGs for people living with MS, the results from this study send a strong message to the medical community regarding the importance of physical activity referral by a physician in this population.

      Declaration of Competing Interest

      Authors report no financial relationships with commercial interests of relevance to this study. A. Hicks received research grant support from the Multiple Sclerosis Society of Canada, and K. Canning received a studentship from the Multiple Sclerosis Society of Canada for the duration of the project.

      Funding

      This work was funded by a grant from the Multiple Sclerosis Society of Canada (EG: 2001)

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