Drop-out, adherence, and compliance in randomized controlled trials of exercise training in multiple sclerosis: Short report.

We documented reporting and rates of drop-out, adherence, and compliance from 40 randomized controlled trials (RCTs) included in our meta-analysis on safety of exercise training (ET) in MS. We adopted definitions and metrics of adherence and compliance provided by the MoXFo adherence group. Drop-out was reported in 100% of the RCTs and approximated 10% for intervention and control conditions. Adherence and compliance were reported in approximately 50% and 10% of the RCTs, respectively, and approximated 80% and 70%, respectively. Standardized metrics for reporting adherence and compliance are important in future RCTs for understanding the impact on outcomes and translation of research evidence into practice.

Randomized Controlled Trial of the Behavioral Intervention for Physical Activity in Multiple Sclerosis Project: Response Heterogeneity and Predictors of Change.

BACKGROUND: We reported that a social cognitive theory-based (SCT), Internet-delivered behavioral intervention increased device-measured minutes/day of moderate-to-vigorous physical activity (MVPA) over a 6-month period among persons with multiple sclerosis (MS). This paper examined the pattern and predictors of heterogeneity in change for MVPA. Based on previous research, we hypothesized that mild MS disability, fewer MS symptoms, lower baseline MVPA, and positive SCT characteristics (e.g., high exercise self-efficacy) would be associated with greater change in MVPA. METHOD: Persons with MS (N = 318) were randomized into behavioral intervention (n = 159) or attention/social contact control (n = 159) conditions that were administered via Internet websites and supported with behavioral coaching. Demographic, clinical, symptom, behavioral, and SCT data were from before the 6-month period of delivering the conditions, and MVPA data were from before and after the 6-month period. We examined heterogeneity based on waterfall plots, box plots, and the Levene statistic. We identified predictors of MVPA change using bivariate correlation and multiple, linear regression analyses per condition. RESULTS: The Levene statistic indicated statistically significant heterogeneity of variances for MVPA change between conditions (p = .003), and the waterfall plots and box plots indicated greater heterogeneity in MVPA change for the behavioral intervention. MVPA change score was correlated with baseline MVPA (r = - .33 and r = - .34, p = .0004 and p = .0001) in both conditions and walking impairment (r = - .188, p = .047) and race (r = .233, p = .014) in the behavioral intervention condition. The regression analysis indicated that baseline MVPA (Standardized B = - .449, p = .000002), self-reported walking impairment (Standardized B = - .310, p = .0008), and race (Standardized B = .215, p = .012) explained 25.6% of variance in MVPA change for the behavioral intervention condition. CONCLUSION: We provide evidence for walking impairment, baseline MVPA, and race as predictors of the heterogeneity in the pattern of MVPA change with a behavioral intervention.

Physical activity together for MS (PAT-MS): Secondary outcomes of a randomized controlled feasibility trial.

BACKGROUND: Care partners provide essential care to those with multiple sclerosis (MS). Dyadic interventions promoting health behaviours have wide-reaching benefits for individuals with MS and their care partners. However, behavioural interventions to promote physical activity in patient-caregiver dyads have yet to be explored in an MS-specific context. This study examined the secondary outcomes of the "Physical Activity Together for Multiple Sclerosis (PAT-MS)" intervention, including dyadic adjustment, caregiving tasks, caregiver quality of life, coping, and MS impact in MS dyads. METHODS: A randomized controlled feasibility trial of the 12-week behavioural PAT-MS intervention. The Dyadic Adjustment Scale, Caregiving Tasks in MS Scale, Caregiver Quality of Life in MS Scale, Coping with MS Caregiving Inventory, and MS Impact Scale measured secondary outcomes of interest. Mixed-model ANOVAs were used to test changes in variables between groups (PAT-MS vs wait-list control) over time. RESULTS: 20 participants, including 10 people with MS (51.4 ± 10.1 years old; median patient-determined disease steps (PDDS) score= 4, IQR= 1.25) and 10 care partners (48.5 ± 12.1 years old) were recruited and randomized. There was no statistically significant effect of the intervention on any of the secondary outcomes (p= 0.67-1.00). However, large effect sizes and condition-by-time interaction effects indicated improvement in dyadic adjustment (d= 1.03, ηp2= 0.45), the criticism-coercion coping subscale (d= -0.93, ηp2= 0.49), and caregiving tasks (d= 1.05, ηp2= 0.52), specifically within psycho-emotional (d= 1.47, ηp2= 0.38) and socio-practical (d= 1.10, ηp2 =0.37) sub-domains of caregiving tasks after the PAT-MS intervention compared to the wait-list condition. CONCLUSION: While this pilot feasibility study was not powered based on the secondary outcomes herein, our findings indicate improvement in dyadic adjustment and emotional and social caregiving tasks, with reduced reliance on criticism-coercion coping in the PAT-MS group compared to controls following the intervention. Findings indicate that PAT-MS may improve dyadic psychosocial well-being of people with moderate-to-severe MS and their care partners, and this should be examined next in a fully-powered study.

Physical Activity Together for Multiple Sclerosis (PAT-MS): A randomized controlled feasibility trial of a dyadic behaviour change intervention.

Background: Many people with advanced multiple sclerosis (MS) and their care-partners do not engage in sufficient physical activity (PA) for health benefits. We developed "Physical Activity Together for MS (PAT-MS)", a 12-week dyadic behavioural intervention, to promote PA among these dyads. Herein, we evaluated the feasibility of PAT-MS before a definitive trial. Methods: A randomized controlled feasibility trial, with 1:1 allocation into the intervention or wait-list control condition. Predefined progression criteria included rates of recruitment, retention, safety, participant satisfaction and adherence. Changes in self-reported and accelerometer-measured PA were assessed at baseline and post-intervention using mixed-factor ANOVAs. Effects sizes were calculated as Cohen's d. Results: The recruitment rate (i.e., 20 participants in 10 months) was not acceptable. However, retention (80%) was acceptable. No serious adverse events were reported. There were high levels of participant satisfaction with the intervention (content (median = 6 out of 7), facilitator (median = 7 out of 7), and delivery (median = 5 out of 7)) and adherence (92% of the group sessions, 83% of the individual support calls, and 80% of the practice activities were completed). There were statistically significant time-by-condition interactions on self-reported PA, steps/day, and %wear time and minutes in sedentary behaviour, and moderate-to-vigorous PA from baseline to post-intervention in people with MS and their family care-partners. Conclusion: PAT-MS appears feasible, safe, and efficacious for PA promotion in MS dyads. We established effect size estimates to power a future definitive trial and identified necessary methodological changes to increase the efficiency of study procedures and improve the quality of the intervention. Trial registration: ClinicalTrials.gov NCT04267185; Registered February 12, 2020, https://clinicaltrials.gov/ct2/show/NCT04267185.

Symptom Management Among Multiple Sclerosis Care Partners in Canada.

BACKGROUND: Managing the heterogeneity and unpredictability of multiple sclerosis (MS) symptoms can be difficult for MS care partners. This study aimed to characterize the symptoms managed by MS care partners, recognize relationships between symptom management difficulty and other aspects of the caregiving role, and identify supplemental sources of care-giving support used by care partners. METHODS: A Canadian cohort of MS care partners completed an online survey capturing care-partner characteristics, care-recipient symptoms, care-partner difficulty with managing symptoms, and sources of caregiving assistance. Descriptive analysis, analysis of variance, and χ2 tests were used to compare differences in care-partner characteristics by symptom management difficulty groups, defined as low (<4 symptoms), medium (5-7 symptoms), and high difficulty (>7 symptoms). RESULTS: Care partners to individuals with MS (N = 475) reported a median of 8 symptoms (IQR = 4) experienced by their care-recipients. The most frequent symptoms reported were fatigue (89.1%), weakness (87.2%), and depression (81.9%). Care partners reported a median of 6 (IQR = 5) symptoms being somewhat or very difficult to manage. Balance or mobility impairments (20.3%), depression (14.3%), and vision difficulties (13.1%) were most frequently reported as very difficult to manage. Assisting with activities of daily living (P < .001) and time spent caregiving (P = .035) varied significantly between symptom management difficulty groups. Additional help available was reported by 77.5%, 17.8%, and 41.6% of care partners reporting low, medium, and high symptom management difficulty, respectively (P < .001). CONCLUSIONS: Care partners of individuals with MS report difficulty in managing multiple, variable symptoms and often have no additional help. These findings suggest that MS care partners experience difficulty managing many diverse symptoms and may benefit from additional support.

Mapping Resilience: Structural Equation Modeling of Psychological Resilience in Multiple Sclerosis Care Partners.

BACKGROUND: Care partners are essential supports to individuals with multiple sclerosis (MS). Both negative and positive outcomes associated with the caregiving role have been reported. Psychological resilience may be an important factor influencing the MS caregiving experience, but an MS-specific model of care partner resilience has yet to be established. This study sought to explore an explicit model of MS care partner resilience. METHODS: Cross-sectional data from 471 Canadian MS care partners were collected via an online survey. Confirmatory factor analysis (CFA) and structural equation modeling (SEM) were used to test measures within a hypothesized model of resilience. Resilience was measured using the 25-item Connor-Davidson Resilience Scale. RESULTS: Following CFA, the hypothesized model was simplified due to the poor fit of several variables. The final model yielded a moderate SEM fit (χ2 = 6030.95, P < .01). Being a woman was associated with greater caregiving tasks (ß = 0.53, P < .001) and poorer spiritual health (ß = -0.35, P < .001). Spiritual health, but not caregiving tasks, had a positive impact on both positive (ß = 0.48, P < .01) and negative coping (ß = 0.49, P = .01). Quality of life and resilience did not have relationships with other variables in the model. However, quality of life had a positive, unidirectional influence on resilience (ß = 0.83, P < .01). CONCLUSIONS: Our findings indicate that spiritual health is an important predictor of coping and should be further explored in MS care partners. Quality of life may act as a precursor to resilience within MS care partners. Further research and exploration into MS care partner resilience is warranted to confirm this exploratory model.

The MoXFo initiative - study design: Considerations related to study design and methodology in exercise research for people with multiple sclerosis.

BACKGROUND: Exercise as a subset of physical activity is a cornerstone in the management of multiple sclerosis (MS) based on its pleiotropic effects, but continued progression of the field requires better future designs and methodologies. OBJECTIVES: This paper outlines the work of the 'Study design and methodology' group of the MoXFo (moving exercise research forward) initiative, and addresses critical aspects and future directions when defining the research question of interest, and subsequently, designing the study and exercise intervention in MS patients. METHODS: The work is based on the formation of an international expert panel formed within the MoXFo initiative. We provide a structured and concise synthesis of exercise-specific MS research challenges and considerations when designing randomized controlled trials (RCTs). RESULTS: Challenges and considerations are presented using the Patient population, Intervention, Comparator, Outcomes, Timing, Setting (PICOTS) framework, thereby forming a new and specific MS exercise PICOTS framework. CONCLUSION: We propose that researchers should carefully consider and align all elements of this MS exercise PICOTS framework when developing future research questions and study designs, ultimately improving the quality of new exercise studies in people with MS.

The MoxFo initiative - outcomes: Outcome measures in studies of exercise training in multiple sclerosis; scoping review of reviews and classification according to the ICF framework.

BACKGROUND: The number of published studies of exercise training in multiple sclerosis (MS) has grown exponentially with increasing numbers of outcomes capturing exercise effects. This has complicated the selection of relevant indicators and interpretation of intervention effects. OBJECTIVES: The Outcomes subgroup of the MoXFo initiative aimed to (1) identify outcome measures and biomarkers in studies of exercise training in MS; (2) systematically map retrieved outcomes to International Classification of Functioning, Disability and Health (ICF) categories; (3) identify gaps where relevant ICF categories have been omitted. METHODS: Electronic databases and registers were searched from 2010 to July 2020 to identify systematic reviews or meta-analyses of controlled trials of exercise training on any outcome in MS. Retrieved outcomes/biomarkers were mapped to the corresponding ICF category. RESULTS: Eighty-one review articles reporting 235 different outcomes were included. The outcomes corresponded to 15 chapters and 45 categories within the ICF. Outcomes mapped primarily to body function (30 categories) and activities and participation (9 categories) components. Few outcomes mapped to body structures (2 categories) or environmental factors (1 category). CONCLUSION: This sets the stage to develop a resource for researchers/clinicians that will aid in the selection of appropriate outcomes/biomarkers when examining exercise effects in MS.

Safety of exercise training in multiple sclerosis: An updated systematic review and meta-analysis.

BACKGROUND: A review of the safety profile of exercise training in multiple sclerosis (MS) has not been conducted since 2013. OBJECTIVE: We undertook a systematic review and meta-analysis of randomised controlled trials (RCTs) of exercise training published since 2013 and quantified estimated population risks of clinical relapse, adverse events (AE) and serious adverse event (SAE). METHODS: Articles reporting safety outcomes from comparisons of exercise training with non-exercise among persons with MS were identified. The risk of bias was established from study's internal validity assessed using Physiotherapy Evidence Database (PEDro). Rates and estimated mean population relative risks (RRs; 95% confidence interval (CI)) of safety outcomes were calculated, and random-effects meta-analysis estimated the mean RR. RESULTS: Forty-six interventions from 40 RCTs (N = 1780) yielded 46, 40 and 39 effects for relapse, AE, adverse effects and SAE, respectively. The mean population RRs ((95% CI), p-value) for relapse, AE and SAE were 0.95 ((0.61, 1.48), p = 0.82), 1.40 ((0.90, 2.19), p = 0.14) and 1.05 ((0.62, 1.80), p = 0.85), respectively. No significant heterogeneity is observed for any outcome. CONCLUSION: In studies that reported safety outcomes, there was no higher risk of relapse, AE, adverse effects or SAE for exercise training than the comparator. Exercise training may be promoted as safe and beneficial to persons with MS.

Arterial stiffness in persons with multiple sclerosis and controls: Does aerobic fitness account for group differences?

Vascular function is worse in multiple sclerosis (MS) than healthy controls perhaps based on differences in aerobic fitness. We compared carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx75) between MS and controls while accounting for aerobic fitness. Aerobic fitness was measured as peak oxygen consumption on a recumbent stepper. cfPWV and AIx75 were measured using applanation tonometry. Persons with MS demonstrated lower aerobic fitness and higher cfPWV, but no difference in AIx75 compared with controls. The difference in cfPWV remained statistically significant after controlling for aerobic fitness, suggesting that arterial stiffness might reflect underlying pathophysiology processes of MS.

Exploring usability characteristics in computer-based digital health technologies for family caregivers of people with chronic progressive conditions: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to map the literature on how usability is considered during the design and/or evaluation of computer-based digital health technologies for family caregivers of persons with chronic progressive conditions. INTRODUCTION: Computer-based digital health technologies offer convenient alternatives for delivering interventions to caregivers of people with chronic progressive conditions. Usability is a critical component of good practice in developing and implementing health and social care technologies; however, we need to determine whether usability is incorporated in the design and/or evaluation of computer-based digital health technologies for caregivers of people with chronic progressive conditions. Within this context, a broad overview of the existing literature on usability in computer-based digital health technologies is needed. INCLUSION CRITERIA: We will include studies published from 2012 to the present that describe usability characteristics of computer-based digital health technologies targeting adult (≥18 years old) family caregivers of people with chronic progressive conditions, regardless of study design or setting. METHODS: We will use the JBI methodology for scoping reviews. We will conduct searches of MEDLINE (Ovid), PsycINFO (Ovid), CINAHL (EBSCOhost), and Web of Science Core Collection to capture eligible studies. After the results are deduplicated, 2 independent reviewers will assess each study for eligibility and extract data from the included studies. Conflicts will be resolved through discussion or with a third reviewer. Data analysis will use a textual narrative synthesis approach. REVIEW REGISTRATION: Open Science Framework osf.io/w4vk5.

Randomized controlled trial of the behavioral intervention for physical activity in multiple sclerosis project: Social cognitive theory variables as mediators.

BACKGROUND: We recently reported in a phase-III, randomized controlled trial that a behavioral intervention based on social cognitive theory (SCT) and delivered through the Internet using e-learning approaches increased device-measured minutes/day of moderate-to-vigorous physical activity (MVPA) over a 6-month period among persons with multiple sclerosis (MS). OBJECTIVE: This planned tertiary outcome paper examined SCT variables as mediators of the behavioral intervention effect on change in device-measured minutes/day of MVPA. METHOD: Persons with MS (N = 318) were randomized into behavioral intervention (n = 159) or attention/social contact control (n = 159) conditions. The conditions were administered over a 6-month period via an Internet website and supported with behavioral coaching by persons who were uninvolved in screening, recruitment, random assignment, and outcome assessments. We collected MVPA and SCT data before and after the 6-month period. The data analysis involved linear mixed modeling on MVPA and SCT outcomes followed by latent change score modeling for examining SCT variables as mediators of the intervention effect on change in MVPA. RESULTS: The linear mixed model indicated statistically significant group by time interactions on device-measured minutes/day of MVPA and scores from SCT measures of exercise self-efficacy, barriers self-efficacy, goal setting, and planning. The effect of the intervention on device-measured minutes/day of MVPA was mediated by the SCT variable of exercise self-efficacy based on the statistical significance of the Wald z-score for the indirect effect in the latent change score model. CONCLUSIONS: This study provides evidence for exercise self-efficacy as a SCT mediator of the behavioral intervention effect on device-measured minutes/day of MVPA in persons with MS.

Primary results of a phase-III, randomized controlled trial of the Behavioral Intervention for increasing Physical Activity in Multiple Sclerosis project.

BACKGROUND: We undertook a phase-III, randomized controlled trial (RCT) that examined the effectiveness of a behavioral intervention based on social cognitive theory (SCT) and delivered through the Internet using e-learning approaches for immediate and sustained increases in physical activity among persons with multiple sclerosis (MS). METHOD: The study followed a parallel group RCT design. Persons with MS (N = 318) were randomized into either behavioral intervention (n = 159) or attention/social contact control (n = 159) conditions. The conditions were administered over a 6-month period by persons who were uninvolved in screening, recruitment, random assignment, and outcome assessment. There was a 6-month follow-up period without access of conditions. We collected outcome data every 6 months over the 12-month period. The primary outcome was device-measured minutes/day of moderate-to-vigorous physical activity (MVPA). The data analysis involved a modified intent-to-treat approach (i.e. those who received the allocated conditions) using a linear mixed model. RESULTS: There was a significant group by time interaction on the primary outcome of device-measured minutes/day of MVPA (p < 0.005). MVPA was increased immediately after the 6-month period in the behavioral intervention compared with control, and this difference was sustained over the 6-month follow-up. CONCLUSION: This study provides evidence for the effectiveness of a widely scalable approach for increasing MVPA in persons with MS.

Vascular function and cognition in persons with multiple sclerosis: Preliminary examination.

BACKGROUND: Cognitive dysfunction is one of the most common consequences of multiple sclerosis (MS). Recent studies have noted a high incidence of vascular comorbidity that might be associated with cognitive decline among persons with MS. However, there is a lack of evidence on vascular biomarkers (e.g., arterial stiffness indices) that are associated with cognition in MS. The current study characterized differences in vascular function between persons with MS and healthy controls, and examined the association between vascular and cognitive function in persons with MS compared with healthy controls. RESULTS: The MS group had significantly worse cognitive performance and higher cfPWV than healthy controls. There were significant bivariate correlations between the Symbol Digit Modalities Test (SDMT) score with AIx75 (rs = -0.45) and cfPWV (rs = 0.30) in the MS sample, but not in healthy controls. Regression analyses further indicated a nonlinear association between cfPWV and the SDMT in the MS sample (p-values for ß coefficients < 0.05; adjusted R2 = 0.10). No significant associations were observed among other cognitive and vascular outcomes. CONCLUSION: Our findings suggest significant associations between arterial stiffness and cognitive processing speed in MS. This preliminary examination provides initial, cross-sectional support for future population-based research on cognitive and vascular function in persons with MS. Such results may be clinically important for developing interventions that focus on regulating vascular dysfunction as an early treatment for preventing cognitive impairment in the MS population.

Prioritizing Components of a Dyadic Physical Activity Intervention for People With Moderate to Severe Multiple Sclerosis and Their Care Partners: A Modified e-Delphi Study.

BACKGROUND: People with moderate to severe multiple sclerosis (MS) and their family care partners do not engage in sufficient physical activity (PA) for health benefits. Dyadic PA interventions need to be developed to benefit each individual and the dyad. The objective of this study was to engage expert stakeholders in prioritizing and refining key intervention content, delivery methods, and the practical/logistical aspects of a dyadic PA intervention for persons with MS and their care partners. METHODS: Thirty-two stakeholders (14 clinicians, 11 people with MS, 5 MS care partners, and 2 representatives of organizations that provide support services for people with MS and/or MS care partners) completed 2 rounds of a modified e-Delphi survey. In round 1, participants rated items across 3 domains: key intervention content (n = 8), delivery methods (n = 9), and practical/logistical aspects (n = 4). Participants contributed additional ideas about these domains, which were incorporated into round 2. Items that did not reach consensus in round 1 were forwarded to round 2 for rerating. Data were analyzed using descriptive statistics and content analysis. RESULTS: A 24-item list of recommendations was generated, including ensuring that presentation of the intervention content encouraged lifestyle activities in addition to exercise, using videoconferencing rather than teleconferencing as a delivery platform, and stressing the importance of flexibility during the support calls. CONCLUSIONS: Feedback will be used to improve the quality of the intervention. The next step in this line of research involves evaluating the refined intervention in a pilot feasibility trial.

Randomized controlled trial of the behavioral intervention for increasing physical activity in multiple sclerosis project: Secondary, patient-reported outcomes.

BACKGROUND: We undertook a randomized controlled trial (RCT) that investigated the effectiveness of a theory-based, Internet-delivered, behavioral intervention focusing on physical activity promotion for immediate and sustained improvements in secondary, patient-reported outcomes (PROs) of function, symptoms, and quality of life (QOL) in multiple sclerosis (MS). METHOD: Persons with MS (N = 318) were recruited from throughout the United States and randomized into behavioral intervention (n = 159) or attention/social contact control (n = 159) conditions. The conditions were administered over a 6-month period by persons who were uninvolved in screening, recruitment, random assignment, and outcome assessment. There was a 6-month follow-up period without intervention access/content. We collected PROs data every 6 months over the 12-month period. The PROs included validated measures of walking and cognitive function, symptoms of fatigue, depression, anxiety, pain, and sleep quality, and QOL. The data analysis involved a modified intent-to-treat approach using a linear mixed model in JMP Pro 16.0. RESULTS: There was a significant group by time interaction on Fatigue Severity Scale scores (p < .01) and physical subscale scores of the Modified Fatigue Impact Scale (p < .05). Scores on both measures decreased immediately after the 6-month period in the behavioral intervention compared with no change in the control condition, and this differential pattern of change was sustained over the 6-month follow-up. There were no group by time interactions on the other PROs. DISCUSSION: This study provides evidence for the effectiveness of a novel, widely scalable approach for physical activity promotion and fatigue management in persons with MS, yet this must be contextualized with the absence of improvements in the other PROs.

Development of a behavioural intervention for cognitive fatigability in multiple sclerosis: Protocol for a pilot and feasibility study.

Background: Up to 90% of people with multiple sclerosis (PwMS) subjectively report fatigue as one of their worst symptoms. Fatigability is an objectively measured component of fatigue. Cognitive fatigability (CF) is a breakdown in task performance following sustained cognitive effort. There is a paucity of interventions targeting CF in MS. The prior success of behavioural interventions at improving subjective fatigue suggests that their adaptation may yield similar results for CF. Given the relationship between CF, sleep quality, and mood, a behavioural intervention targeting these factors, such as cognitive behavioural therapy (CBT), is warranted. Given the multidimensional nature of fatigue, a multifaceted approach targeting lifestyle factors and coping (e.g., fatigue management education supplemented by CBT for insomnia and exercise) might prove efficacious. Aim: We describe a protocol for a pilot feasibility study to design and implement a multi-dimensional behavioural intervention to improve CF in PwMS. Methods: Stage 1: development of a multi-dimensional group-based videoconference-delivered behavioural intervention based on a previously successful fatigue management program for PwMS. A facilitator manual will be drafted. Course material will focus on four themes: body (sleep and physical activity), mood (impact of depression and anxiety), mind (cognitive contributions), and context (pacing and communication). Stage 2: a needs assessment survey will be completed by 100 PwMS for input on what factors are important contributors to their CF. Modifications will be made to the course material and manual. Stage 3: the facilitator-delivered intervention will include 20 PwMS. After baseline assessment, participants will attend weekly 70-min videoconference group sessions for 8 weeks, including homework assignments. Follow-up assessment will re-evaluate outcomes. Stage 4: analysis and dissemination of results. The primary outcome is improvement in CF. Additional feasibility outcomes will determine if a randomized control trial (RCT) is pursued. Stage 5: refine the intervention based on outcomes and feedback from participants. Determining which aspects participants felt were most effective will help inform RCT design. Conclusion: The long-term goal is to ensure that PwMS have access to effective interventions in real-world settings to improve quality of life and enhance their ability to participate in cognitively demanding activities that they enjoy.

A continuum of languishing to flourishing: exploring experiences of psychological resilience in multiple sclerosis family caregivers.

PURPOSE: Resilience research in family caregiving in chronic neurological conditions is growing, but multiple sclerosis (MS) caregivers are noticeably absent from this body of work. MS caregivers represent a unique population due to the disease's early onset, prolonged life expectancy, and heterogeneity. As such, this study aimed to explore MS caregivers' conceptualizations of resilience, examine MS caregivers' experiences of resilience development, and determine which assets and resources influence resilience in this role. METHODS: Twenty-four Canadian MS caregivers were recruited. Semi-structured in-depth interviews were conducted with questions derived from an ecological resilience framework. Data were analysed using reflexive thematic analysis. RESULTS: Themes constructed a cyclical resilience model, beginning with encounters with hardship and extending to thriving adjustment. Subthemes included reports of additive challenges, impactful individual and community resources, and multi-level adaptive pathways. Within this cycle, the achievement of healthy adjustment exerted a positive feedback function and informed future responses to lifelong challenges. CONCLUSIONS: Despite the salience of resilience processes within caregiver testimonies, inadequate resources at societal levels were evident. These findings afford researchers and decision-makers relevant information for designing and implementing resilience-building interventions for MS caregivers that attend to contextual factors and current systemic support deficiencies.

Lessons learned from clinical trials of exercise and physical activity in people with MS - guidance for improving the quality of future research.

The body of research on exercise and physical activity among persons with multiple sclerosis(MS) has expanded rapidly in quantity, but not necessarily quality, over the past 20+ years. There is evidence for beneficial effects of exercise and physical activity on immune cells and neurotrophic factors, brain structure and function, walking and cognitive performance, fatigue, depression, and pain, and quality of life among persons with MS. Nevertheless, there is heterogeneity in the outcomes of exercise and physical activity, and a recognition of substantial challenges for improving the effectiveness of those behaviors in MS. To move the field forward, members of the National MS Society physical wellness research working-group pooled collective experiences for identifying challenges, logistic complexities, and opportunities for researchers in designing and conducting interventions of exercise and physical activity among persons with MS. We examined the scope of our experiences and identified collective "lessons learned" regarding the behaviors themselves; study design features and stage of research; study setting, safety, and sample selection; and implementation of randomized controlled trials(RCTs) and treatment fidelity. This paper provides a resource that can inform researchers, particularly new investigators or established investigators transitioning into MS, on conducting high-quality RCTs on exercise and physical activity in MS.

Assessing proprioceptive acuity in people with multiple sclerosis.

Background: Proprioceptive acuity and impairments in proprioceptively guided reaches have not been comprehensively examined in people with multiple sclerosis (MS). Objective: To examine proprioceptive acuity in people with MS who self-report and who do not self-report upper limb (UL) impairment, and to determine how people with MS reach proprioceptive targets. Methods: Twenty-four participants with MS were recruited into two groups based on self-reported UL impairment: MS-R (i.e. report UL impairment; n = 12) vs. MS-NR (i.e. do not report UL impairment; n = 12). Proprioception was assessed using ipsilateral and contralateral robotic proprioceptive matching tasks. Results: Participants in the MS-R group demonstrated worse proprioceptive acuity compared to the MS-NR group on the ipsilateral and contralateral robotic matching tasks. Analyses of reaches to proprioceptive targets further revealed that participants in the MS-R group exhibited deficits in movement planning, as demonstrated by greater errors at peak velocity in the contralateral matching task in comparison to the MS-NR group. Conclusion: Our findings suggest that people with MS who self-report UL impairment demonstrate worse proprioceptive acuity, as well as poorer movement planning in comparison to people with MS who do not report UL impairment.