Perceived and physiological strains of societal participation in people with multiple sclerosis: a real-time assessment study.

OBJECTIVE: To examine the relationship between perceived and physiological strains of real-time societal participation in people with multiple sclerosis. DESIGN: Observational study. SUBJECTS/PATIENTS: 70 people with multiple sclerosis. METHODS: Perceived and physiological strain of societal participation (10 participation-at-location and 9 transport domains) were measured in real time using the Whereabouts smartphone app and Fitbit over 7 consecutive days. Longitudinal relationships between perceived (1 not strenuous to 10 most strenuous) and physiological strains (heart rate reserve) were examined using mixed-model analyses. Type of event (participation-at-location or transport) was added as covariate, with further adjustments for fatigue and walking ability. RESULTS: Median perceived strain, summarized for all societal participation domains, varied between 3 and 6 (range: 1-10), whereas physiological strain varied between 18.5% and 33.2% heart rate reserve. Perceived strain (outcome) and physiological strain were not associated (ß -0.001, 95%CI -0.008; 0.005, with a 7-day longitudinal correlation coefficient of -0.001). Transport domains were perceived as less strenuous (ß -0.80, 95%CI -0.92; -0.68). Higher fatigue levels resulted in higher perceived strain (all societal participation domains) (ß 0.05, 95%CI 0.02; 0.08). CONCLUSION: Societal participation resulted in low-to-moderate perceived and physiological strain. Perceived and physiological strain of societal participation were unrelated and should be considered different constructs in multiple sclerosis.

The presence of attentional and interpretation biases in patients with severe MS-related fatigue.

OBJECTIVE: Severe fatigue is a prevalent and disabling symptom in multiple sclerosis (MS). This study tested if a fatigue- and physical activity-related attentional bias (AB) and a somatic interpretation bias (IB) are present in severely fatigued patients with MS. Biases were compared to healthy controls and patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). METHOD: Severely fatigued patients with MS or ME/CFS and healthy controls completed a Visual Probe Task (VPT) assessing fatigue- and physical activity-related AB and an IB task that assesses the tendency to interpret ambiguous information in either a somatically threatening way or in a more neutral manner. The VPT was completed by 38 MS patients, 44 ME/CFS patients, and 46 healthy controls; the IB task was completed by 156, 40 and 46 participants respectively. RESULTS: ANOVA showed no statistically significant group differences in a fatigue-related AB or physical activity-related AB (omnibus test of interaction between topic × condition: F2,125 = 1.87; p = .159). Both patient groups showed a tendency to interpret ambiguous information in a somatically threatening way compared to healthy controls (F1,2 = 27.61, p < .001). This IB was significantly stronger in MS patients compared to ME/CFS patients. IB was significantly correlated with cognitive responses to symptoms in MS patients. CONCLUSION: MS patients tend to interpret ambiguous information in a somatically threatening way. This may feed into unhelpful ways of dealing with symptoms, possibly contributing to the perpetuation of severe fatigue in MS.

Relative aerobic load of walking in people with multiple sclerosis.

OBJECTIVE: To examine the energy demand of walking relative to aerobic capacity in people with multiple sclerosis. DESIGN: Cross-sectional cohort study. PATIENTS: A total of 45 people with multiple sclerosis (32 females), median disease duration 15 years (interquartile range (IQR) 9; 20), median Expanded Disability Status Scale 4 (min-max range: 2.0; 6.0). METHODS: Aerobic capacity, derived from a cardiopulmonary exercise test and gas exchange measurements, assessed during a 6-min overground walk test at comfortable speed, were analysed. The relative aerobic load of walking was determined as the energy demand of walking relative to oxygen uptake at peak and at the first ventilatory threshold. Healthy reference data were used for clinical inference. RESULTS: People with multiple sclerosis walk at a mean relative aerobic load of 60.0% (standard deviation 12.8%) relative to peak aerobic capacity, and 89.1% (standard deviation 19.9%) relative to the first ventilatory threshold. Fourteen participants walked above the first ventilatory threshold (31%). Peak aerobic capacity was reduced in 45% of participants, and energy demands were increased in 52% of participants. CONCLUSION: People with multiple sclerosis walk at a relative aerobic load close to their first ventilatory threshold. A high relative aerobic load can guide clinicians to improve aerobic capacity or reduce the energy demands of walking.

Effectiveness of a blended booster programme for the long-term outcome of cognitive behavioural therapy for MS-related fatigue: A randomized controlled trial.

BACKGROUND: Cognitive behavioural therapy (CBT) reduces MS-related fatigue. However, studies on the long-term effects show inconsistent findings. OBJECTIVE: To evaluate whether a blended booster programme improves the outcome of CBT for MS-related fatigue on fatigue severity at 1-year follow-up. METHOD: A multicentre randomized clinical trial in which 126 patients with MS were allocated to either a booster programme or no booster programme (control), after following 20-week tailored CBT for MS-related fatigue. Primary outcome was fatigue severity assessed with the Checklist Individual Strength fatigue subscale 1 year after start of treatment (T52). Mixed model analysis was performed by a statistician blinded for treatment-allocation to determine between-group differences in fatigue severity. RESULTS: Fatigue severity at 1-year follow-up did not differ significantly between the booster (N = 62) and control condition (N = 64) (B = -2.01, 95% confidence interval (CI) = -4.76 to 0.75). No significant increase in fatigue severity was found at T52 compared with directly post-treatment (T20) in both conditions (B = 0.44, 95% CI = -0.97 to 1.85). CONCLUSION: Effects of CBT were sustained up to 1 year in both conditions. The booster programme did not significantly improve the long-term outcome of CBT for MS-related fatigue. TRIAL REGISTRATION: Dutch Trial Register (NTR6966), registered 18 January 2018 https://www.trialregister.nl/trial/6782.

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.

Blended versus face-to-face cognitive behavioural therapy for severe fatigue in patients with multiple sclerosis: A non-inferiority RCT.

BACKGROUND: Cognitive behavioural therapy (CBT) reduces multiple sclerosis (MS)-related fatigue. Implementation of face-to-face CBT is hindered by limited treatment capacity and traveling distances to treatment locations. OBJECTIVE: Evaluate whether blended CBT (online treatment modules supported with guidance by a therapist) is non-inferior to face-to-face CBT in reducing fatigue severity in severely fatigued patients with MS. METHOD: A non-inferiority multicentre randomized clinical trial, in which 166 patients with MS were allocated to either face-to-face or blended CBT. Primary outcome was fatigue severity assessed with the Checklist Individual Strength fatigue subscale directly post-treatment (week 20). Mixed model analysis was used by a statistician blinded for allocation to determine between-group differences post-treatment. The upper limit of the 95% confidence interval (CI) was compared to a pre-specified non-inferiority margin of 5.32. RESULTS: Blended CBT (N = 82) was non-inferior to face-to-face CBT (N = 84) (B = 1.70, 95% CI: -1.51 to 4.90). Blended CBT significantly reduced therapist time (B = -187.1 minutes, 95% CI: 141.0-233.3). Post hoc analysis showed more improvement (B = -5.35, 95% CI: -9.22 to -1.48) when patients received their preferred treatment. No harm related to treatment was reported. DISCUSSION: Blended CBT is an efficient alternative to face-to-face CBT. Offering the preferred CBT format may optimize treatment outcome.

Brain-derived neurotrophic factor, neurofilament light and glial fibrillary acidic protein do not change in response to aerobic training in people with MS-related fatigue - a secondary analysis of a randomized controlled trial.

BACKGROUND: Neuroinflammation and neurodegeneration are pathological hallmarks of multiple sclerosis (MS). Brain-derived neurotrophic factor (BDNF), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) are blood-based biomarkers for neurogenesis, axonal damage and astrocyte reactivity, respectively. We hypothesize that exercise has a neuroprotective effect on MS reflected by normalization of BDNF, NfL and GFAP levels. OBJECTIVES: To investigate the neuroprotective effect of aerobic training (AT) compared to a control intervention on blood-based biomarkers (i.e. BDNF, NfL, GFAP) in people with MS (pwMS). METHODS: In the TREFAMS-AT (Treating Fatigue in Multiple Sclerosis - Aerobic Training) study, 89 pwMS were randomly allocated to either a 16-week AT intervention or a control intervention (3 visits to a MS nurse). In this secondary analysis, blood-based biomarker concentrations were measured in 55 patients using Simoa technology. Changes in pre- and post-intervention concentrations were compared and between-group differences were assessed using analysis of covariance (ANCOVA). Confounding effects of age, sex, MS-related disability assessed using the Expanded Disability Status Scale (EDSS), MS duration, use of disease-modifying medication, and Body Mass Index were considered. RESULTS: Blood samples were available for 30 AT and 25 control group participants (mean age 45.6 years, 71% female, median disease duration 8 years, median EDSS score 2.5). Within-group changes in both study groups were small and non-significant, with the exception of BDNF in the control group (median (interquartile range) -2.1 (-4.7; 0)). No between-group differences were found for any biomarker: BDNF (ß = 0.11, 95%CI (-3.78 to 4.00)), NfL (ß = -0.04, 95%CI (-0.26 to 0.18)), and GFAP (ß = -0.01, 95%CI (-0.16 to 0.15)), adjusted for confounders. CONCLUSION: Aerobic exercise therapy did not result in statistically significant changes in the tested neuro-specific blood-based biomarkers in people with MS. TRIAL REGISTRATION: this study is registered under number ISRCTN69520623 (https://www.isrctn.com/ISRCTN695206).

Determinants of spoken language comprehension in children with cerebral palsy.

PURPOSE: To identify determinants of spoken language comprehension (SLC) in children with cerebral palsy (CP). MATERIALS AND METHODS: Cross-sectional data of 207 children with CP were included: 82 toddlers (18 months-3;11 years), 59 preschool children (4;0-5;11 years), and 66 schoolchildren (6;0-8;11 years), across all Gross Motor Function Classification System (GMFCS) levels. SLC was assessed using the Computer-Based instrument for Low motor Language Testing (C-BiLLT). Potential determinants were retrieved from medical files and through parental questionnaires. Per developmental stage, multivariable regression analyses were used to assess determinants of SLC. RESULTS: Fifty-nine percent of the children showed below average SLC. Significant determinants for SLC differed per developmental stage. In toddlers: age, motor type, functional communication and speech function (R2 = 0.637); in preschool children: functional communication, speech function and language activities (R2 = 0.820), and in schoolchildren: functional communication, intellectual functioning and arm-hand functioning (R2 = 0.807). For all developmental stages, functional mobility was not a significant determinant. CONCLUSIONS: A large proportion of children with CP across all GMFCS levels have SLC impairments. Findings indicate that SLC is strongly determined by functional communication classified with CFCS. We recommend standardized assessment and monitoring of SLC in all children with CP. IMPLICATIONS FOR REHABILITATIONChildren across all GMFCS levels can experience difficulties in spoken language comprehension.At all developmental stages, functional communication (classified with CFCS) is an important determinant of spoken language comprehension.Standardized assessment and monitoring of spoken language comprehension, language production, speech, and communication of all children with CP, is strongly recommended.When children show below average performances, especially in spoken language comprehension, intervening with speech and language therapy and guidance for parents, is advised.

The relationship between energy cost of walking, ankle push-off and walking speed in persons with multiple sclerosis.

BACKGROUND: The energy cost of walking (ECw) is an important indicator of walking dysfunction in persons with multiple sclerosis (PwMS). However, its underlying causes and its relation with ankle push-off and walking speed are not well understood. RESEARCH QUESTION: What is the contribution of ankle push-off and walking speed to increased ECw in PwMS? METHODS: Ten PwMS with walking limitations and 10 individually gender- and age-matched healthy controls (HC) were included. All participants performed two 6-min walking trials on a treadmill at comfortable walking speed (CWS of PwMS) and fast walking speed (FWS, 130 % of CWS of PwMS). Kinetics and metabolic cost were evaluated. Generalized estimating equations were performed to investigate effects of group and walking speed, and their interaction. Spearman correlations were conducted to examine whether ECw was related to ankle push-off in PwMS, controlling for differences in walking speed in PwMS. RESULTS: ECw at matched walking speed was significantly higher in PwMS compared to HC. Kinetic parameters were not different between the most impaired leg in PwMS and HC at matched walking speed, but asymmetry between both legs of PwMS was observed. At FWS, ECw reduced and ankle push-off increased similarly in both groups. ECw was inversely related to peak ankle power of the most impaired leg in PwMS at CWS. SIGNIFICANCE: Slow walking speed is one factor that contributes to increased ECw in PwMS. Furthermore, PwMS who had a higher ECw showed a lower peak ankle power, independent of walking speed. This indicates that ankle push-off could be a contributor to increased ECw.

Convergent validity of functional communication tools and spoken language comprehension assessment in children with cerebral palsy.

BACKGROUND: The majority of children with cerebral palsy (CP) experience challenges in functional communication from a young age. A pivotal aspect of functional communication is language comprehension. A variety of classification systems and questionnaires are available to classify and describe functional communication skills in children with CP. A better understanding of the convergent validity of (subsections of) these tools, as well as their relationship with spoken language comprehension, will be valuable in both clinical practice and research. AIMS: To investigate the convergent validity of (subsections of) functional communication tools and the relationship with spoken language comprehension in children with CP. METHODS & PROCEDURES: Cross-sectional data on 138 children were subdivided into three developmental stages based on (Dutch) educational phases: ages 18 months-3;11y (n = 59), 4;0-5;11 years (n = 37) and 6;0-8;11 years (n = 42). The following functional communication tools were used to classify and describe functional communication: Communication Function Classification System (CFCS), subscales of the Caregivers Priorities and Child Health Index of Life with Disabilities-Dutch Version (CPCHILD-DV) and the Focus on Communication Under Six-34 (FOCUS-34) questionnaire. Spoken language comprehension was assessed with the Computer-Based instrument for Low motor Language Testing (C-BiLLT). Correlations between the functional communication tools, and with the C-BiLLT, were calculated using Pearson's and Spearman's correlation coefficients. It was hypothesized a priori that correlations of at least 0.60 suggest good convergent validity. OUTCOMES & RESULTS: At all developmental stages, a significant ordered decreasing tendency of communication outcomes was found across CFCS levels; lower CFCS levels were associated with lower scores on the CPCHILD-DV and FOCUS-34, and with a lower level of spoken language comprehension (C-BiLLT). Correlation coefficients of the functional communication tools exceeded 0.60 at all developmental stages. Correlations between C-BiLLT raw scores and the functional communication tools varied between 0.351 and 0.591 at developmental stage 18 months-3;11 years, between 0.781 and 0.897 at developmental stage 4;0-5;11 years, and between 0.635 and 0.659 at developmental stage 6;0-8;11 years. CONCLUSIONS & IMPLICATIONS: The functional communication tools assessed in this study showed convergent validity at all developmental stages. The CFCS, currently most widely used in paediatric rehabilitation, is adequate in the classification of functional communication. However, for more detailed clinical goal setting and evaluation of change in functional communication, the additional use of FOCUS-34 or CPCHILD-DV is recommended. WHAT THIS PAPER ADDS: What is already known on the subject A range of functional communication tools are available that help describe and classify functional communication in children with CP. These include the CFCS, subsections of CPCHILD-DV and FOCUS-34. The CFCS classifies functional communication in daily life with familiar and unfamiliar partners. Specific subsections of the CPCHILD-DV and FOCUS-34 include items that pertain to communicative participation. The innovative C-BiLLT provides a standardized method to assess spoken language comprehension in children with CP and significant motor impairments. What this paper adds to existing knowledge In the present study, convergent validity was confirmed between CFCS and specific subsections of the CPCHILD-DV and FOCUS-34. Correlations between these functional communication tools and the C-BiLLT were moderate to strong. What are the potential or actual clinical implications of this work? For clinical and research purposes (for instance, accurate prescription of augmentative and alternative communication-AAC), healthcare and educational professionals together with parents need to know how functional communication tools converge and how functional communication levels relate to the comprehension of spoken language. The CFCS provides a valid classification of functional communication abilities in children with CP. However, to measure change in functional communication and to evaluate treatment outcomes, use of additional functional communication tools such as the CPCHILD-DV and FOCUS-34 is recommended. When discrepancies are found between communicative abilities and spoken language comprehension, it is strongly recommended that valid tools are used in a more detailed examination of the child's spoken language comprehension skills and functional communication.

A Smartphone Application to Assess Real-Time and Individual-Specific Societal Participation: A Development and Usability Study.

OBJECTIVE: To develop a mobile health app to assess individual-specific meaningful societal participation in real time and to evaluate its usability. DESIGN: Development and usability study. SETTING: General community. PARTICIPANTS: Persons with multiple sclerosis (PwMS) utilized the app for 7 consecutive days. In total, 72 PwMS and smartphone owners were included in the analysis (N=72). INTERVENTIONS: Using location tracking, the newly developed Whereabouts app generates an individual-specific timeline of societal participation activities each day, consisting of location and transportation intervals. Subsequently, this timeline is real time enriched by the user with self-reported ratings of meaningfulness and perceived strain of these societal participation activities. The app is based on the International Classification of Functioning, Disability and Health and was developed in an iterative process. MAIN OUTCOME MEASURE(S): Usability of the newly developed Whereabouts app was evaluated by analyzing the effectiveness, efficiency, and user satisfaction. RESULTS: Regarding effectiveness, the app correctly assessed the type, frequency, and duration of different societal participation activities for 96.1% of the participation activities. The self-reported ratings of societal participation varied for meaningfulness (range, 5-8), perceived strain (range, 2-6), and meaningfulness of the perceived strain (range, 5-8). The latter 2 were highly correlated (r=0.857). With regards to efficiency, 3.9% of the generated participation activities had to be excluded due to inaccuracy or incompleteness. Relating to user satisfaction, 57.3% of PwMS reported that they were satisfied with the usability of the app and 59.7% stated that it gave a realistic overview of their daily activities. However, 54.4% PwMS missed the possibility to specify activities at home, to add activities in more detail, and to correct mistakes. CONCLUSIONS: The Whereabouts app demonstrates usability in assessing real-time, individual-specific meaningful societal participation. Improvements are recommended, such as the possibility to specify participation activities and to generate a graphic overview.

Surgical complications of intrathecal baclofen in children: A single centre, 20-year retrospective cohort study.

INTRODUCTION: Complications of intrathecal baclofen treatment (ITB) with an implanted pump can be severe and require surgery. Surgical implantation techniques and catheter materials for continuous ITB treatment have improved over the past years with the aim to reduce complications. OBJECTIVE: To assess: 1) the type and rate of complications of ITB that require surgical intervention, 2) which risk factors influence the occurrence of complications, and, specifically, 3) whether complication rate is influenced by type of catheter used. METHODS: A retrospective cohort study was conducted including all children (<18 years old) in one university medical center with pump implantation between 2001 and 2017. All complications requiring surgery were recorded. Risk factors for surgical intervention were determined using multiple logistic regression analysis. Catheter related complications between two types of catheters (silicone vs coated) were compared. RESULTS: In total, 88 complications of ITB treatment requiring surgery were found in 47 (36.2%) out of 130 children. These included catheter-related complications (55.7% of all complications), infections (21.6%), cerebrospinal fluid leakage (14.8%), and pump-related complications (7.9%). The silicone catheter type, used until 2012, was found to be a significant risk factor for complications (Odds Ratio 3.75; 95% CI: 1.30-10.83). Since the introduction of the coated catheter type, in 2012, the rate of catheter-related complications decreased, from 0.15 to 0.10 complications per pump year. CONCLUSION: The rate of surgical complications of intrathecal baclofen in children is high, and most frequently catheter-related. The number of complications decreased since the introduction of a new, coated, catheter in 2012. This study helps to inform children and their caregivers about the risk of possible complications of ITB, and to identify directions for future improvement of ITB care.

Proposal to extend the PROMIS® item bank v2.0 'Ability to Participate in Social Roles and Activities': item generation and content validity.

PURPOSE: Previous research indicated that the Patient-Reported Outcomes Measurement Information System (PROMIS®) item bank v2.0 'Ability to Participate in Social Roles and Activities' may miss subdomains of social participation. The purpose of this study was to generate items for these missing subdomains and to evaluate their content validity. METHODS: A three-step approach was followed: (1) Item generation for 16 International Classification of Functioning Disability and Health subdomains currently not covered by the item bank; (2) Evaluation of content validity of generated items through expert review (n = 20) and think-aloud interviews with a purposeful sample of people with and without (chronic) health conditions (n = 10), to assess item comprehensibility, relevance, and comprehensiveness; and 3) Item revision based on the results of step 2, in a consensus procedure. RESULTS: First, 48 items were generated. Second, overall, content experts indicated that the generated items were relevant. Furthermore, based on experts' responses, items were simplified and 'participation in social media' was identified as an important additional subdomain of social participation. Additionally, 'participating in various social roles simultaneously' was identified as a missing item. Based on the responses of the interviewed adults items were simplified. Third, in total 17 items, covering 17 subdomains, were proposed to be added to the original item bank. DISCUSSION: The relevance, comprehensibility and comprehensiveness of the 17 proposed items were supported. Whether the proposed extension of the item bank leads to better psychometric properties of the item bank should be tested in a large-scale field study.

Moving exercise research in multiple sclerosis forward (the MoXFo initiative): Developing consensus statements for research.

Exercise as a subset of physical activity is a cornerstone in the management of multiple sclerosis (MS) based on its pleotropic effects. There is an exponential increase in the quantity of research on exercise in MS, yet a number of barriers associated with study content and quality hamper rapid progress in the field. To address these barriers and accelerate discovery, a new international partnership of MS-related experts in exercise has emerged with the goal of advancing the research agenda. As a first step, the expert panel met in May 2018 and identified the most urgent areas for moving the field forward, and discussed the framework for such a process. This led to identification of five themes, namely "Definitions and terminology," "Study methodology," "Reporting and outcomes," "Adherence to exercise," and "Mechanisms of action." Based on the identified themes, five expert groups have been formed, that will further (a) outline the challenges per theme and (b) provide recommendations for moving forward. We aim to involve and collaborate with people with MS/MS organizations (e.g. Multiple Sclerosis International Federation (MSIF) and European Multiple Sclerosis Platform (EMSP)) in all of these five themes. The generation of this thematic framework with multi-expert perspectives can bolster the quality and scope of exercise studies in MS that may ultimately improve the daily lives of people with MS.

Fatigue Profiles in Patients with Multiple Sclerosis are Based on Severity of Fatigue and not on Dimensions of Fatigue.

Fatigue related to Multiple Sclerosis (MS) is considered a multidimensional symptom, manifesting in several dimensions such as physical, cognitive, and psychosocial fatigue. This study investigated in 264 patients with severe primary MS-related fatigue (median MS duration 6.8 years, mean age 48.1 years, 75% women) whether subgroups can be distinguished based on these dimensions. Subsequently, we tested whether MS-related fatigue consists of a single common unidimensional factor. Subscale scores on four self-reported fatigue questionnaires, including the Checklist of Individual Strength, the Modified Fatigue Impact Scale, the Fatigue Severity Scale and the SF36 vitality, were used in a cluster analysis to identify patients with similar fatigue characteristics. Next, all 54 items were included in exploratory factor analysis to test unidimensionality. Study results show that in patients with a treatment indication for primary MS-related fatigue, fatigue profiles are based on severity and not on the various dimensions of fatigue. The three profiles found, suggested one underlying fatigue dimension, but this could not be confirmed. Factor analysis of all 54 items resulted in 8 factors, confirming the multidimensional construct of the included fatigue questionnaires.

Testing non-inferiority of blended versus face-to-face cognitive behavioural therapy for severe fatigue in patients with multiple sclerosis and the effectiveness of blended booster sessions aimed at improving long-term outcome following both therapies: study protocol for two observer-blinded randomized clinical trials.

BACKGROUND: Cognitive behavioural therapy (CBT) has been found to be effective in reducing fatigue severity in MS patients directly following treatment. However, long-term effects are inconsistent leaving room for improvement. In addition, individual face-to-face CBT draws heavily on limited treatment capacity, and the travel distance to the treatment centre can be burdensome for patients. Therefore, we developed "MS Fit", a blended CBT for MS-related fatigue, based on a face-to-face CBT protocol found effective in a previous study, and "MS Stay Fit", internet-based booster sessions to improve long-term effectiveness of CBT for MS-related fatigue. This article presents the protocol of two randomised clinical trials (RCTs) conducted within one study investigating (1) the non-inferiority of MS Fit compared with evidence-based face-to-face CBT for MS-related fatigue and (2) the effectiveness of MS Stay Fit on the long-term outcome of fatigue compared with no booster sessions. METHODS/DESIGN: The first part of this study is an observer-blinded non-inferiority multicentre RCT, in which 166 severely fatigued MS patients will be randomly assigned (1:1 ratio, computer-generated sequence) to either face-to-face CBT or blended CBT (MS Fit) for fatigue. The primary endpoint is at 20 weeks after baseline. After this post-treatment assessment, patients will be randomly assigned again (1:1 ratio, computer generated sequence) to either MS Stay Fit consisting of two booster sessions at 2 and 4 months after end of treatment or no booster sessions. The primary endpoint of the second study is 52 weeks after baseline. Primary outcome measure in both studies is fatigue severity assessed with the fatigue severity subscale of the Checklist Individual Strength (CIS20r). Outcomes will be assessed at baseline (T0), at the end of treatment (T20), and after 39 and 52 weeks (T39 and T52). DISCUSSION: If MS Fit is found to be non-inferior to face-to-face CBT, it will improve the accessibility of this treatment. In addition, the study aims to test whether it is possible to improve long-term effectiveness of CBT for MS-related fatigue with MS Stay Fit. TRIAL REGISTRATION: Dutch Trial Register (NTR6966), registered 18 January 2018 https://www.trialregister.nl/trial/6782 WORLD HEALTH ORGANIZATION (WHO) TRIAL REGISTRATION DATA SET: All items from the WHO Trial Registration Data Set can be found within the protocol.

Assessing life balance of European people with multiple sclerosis: A multicenter clinimetric study within the RIMS network.

BACKGROUND: Life balance is defined as "a satisfying pattern of daily activity that is healthful, meaningful, and sustainable to an individual within the context of his or her current life circumstances". To assess life balance, the self-report instrument Life Balance Inventory (LBI) has been developed in the US. The aim of this study was to evaluate cross-cultural, construct validity and test-retest reliability of translated versions of the LBI in people with multiple sclerosis (MS) within different European cultures (Dutch, Flemish, Slovenian, and Spanish). METHOD: The LBI was translated according to the principles of forward/backward translation and the cultural adaption process of patient-reported outcomes and evaluated in people with MS in each country/language area. LBI (score range 1-3; higher scores refer to better balance) was registered twice with an interval of 7 days to evaluate test-retest reliability using Intraclass Correlation Coefficients (ICCs) and Bland Altman analyses. To evaluate construct validity, Pearson correlations of the LBI with quality of life, fatigue, depression and self-efficacy were explored. RESULTS: The total sample (n = 313, 50 ± 11 years of age, MS duration 13 ± 8 years) consisted of five subsamples: Dutch (n = 81, 74% women, 54 ± 9.6 years of age), Flemish 1 (n = 42, 57% women, 49 ± 12 years), Flemish 2 (n = 105, 63% women, 50 ± 10.6 years), Slovenian (n = 48, 79% women, 44 ± 11.2 years) and Spanish (n = 37, 62% women, 47 ± 9.0 years). Baseline total LBI scores differed between subsamples (F(4, 312)=7.19, p < 0.001). ICC [95% CI] of total LBI was 0.88 [0.83-0.92] (Flemish 2), 0.65 [0.39-0.82] (Flemish 1), 0.55 [0.37-0.69] (Dutch), 0.45 [0.15-0.67] (Spanish) and 0.35 [0.07-0.59] (Slovenian). Systematic error was present in one sample; no proportional bias occurred. Correlations ranged from 0.05 to 0.55 for quality of life and self-efficacy, from -0.50 to 0.05 for fatigue and from -0.44 to -0.28 for depression, not fully supporting the hypotheses. CONCLUSION: The study results provide limited support for test-retest reliability, cross-cultural and construct validity of the LBI in different European subsamples. Although LBI may serve as a supportive tool in goalsetting in rehabilitation, the current version of LBI is not recommended for (international) research purposes.

Evidence-Based Rehabilitation for Multiple Sclerosis Made Easy: The Online Applying Evidence with Confidence (APPECO) Platform.

With the current rate in growth of evidence in multiple sclerosis (MS) rehabilitation, systematic reviews and clinical guidelines typically lag behind the most currently published research findings. In addition, most health care professionals lack the time, resources, or adequate skills to identify and evaluate new evidence, and hands-on tools to implement the latest evidence into clinical practice are often lacking or not readily available. The Applying Evidence with Confidence (APPECO) platform is a newly developed online tool that addresses these key challenges. APPECO was initiated as a proof-of-concept for the common MS symptoms fatigue and cognitive function. Subsequently, intervention studies about depression, pain, and mobility were added. APPECO currently hosts detailed information from 250 randomized clinical trials, 293 interventions, and 1250 effect sizes on 53 patient outcomes. Few studies with high quality (ie, low risk of bias) are available specifically designed to test the benefits of MS rehabilitation on fatigue (n = 5 [2.4%]), cognitive function (n = 4 [1.6%]), and depression (n = 2 [0.8%]). No high-quality studies were included for pain and mobility. APPECO has the potential to address key challenges in evidence-based rehabilitation medicine for MS and to facilitate swift knowledge translation from evidence into clinical practice. Sustainability of APPECO depends on a continuous resource impulse (eg, financial, time, editorial management, platform maintenance) to ensure up-to-date information across all relevant MS symptoms and activity limitations (≈2-6 randomized controlled trials per month). Ways to optimize knowledge translation in the absence of high-quality evidence in APPECO need to be explored further.

"I Will Respect the Autonomy of My Patient": A Scoping Review of Shared Decision Making in Multiple Sclerosis.

BACKGROUND: Patient autonomy is a bioethical principle that was strengthened in the revised Declaration of Geneva. Shared decision making (SDM) is particularly relevant in the management of multiple sclerosis (MS) because many preference-sensitive decisions have to be made during the disease course. We aimed to summarize the available evidence on SDM in the MS field and to inform future research and practice. METHODS: We performed a scoping review by searching MEDLINE (past 5 years). Studies were included if they reported primary/secondary research and focused on SDM related to people with MS. Data were grouped into topics, with results presented in narrative form. RESULTS: From 865 references, we included 55 studies conducted mostly in Europe. Half of the studies were observational, followed by qualitative (20%), mixed-methods (17%), randomized controlled trials (RCTs, 5%), quasi-experimental (5%), and reviews (4%). Most studies addressed people with relapsing-remitting MS (85%); the remaining addressed health care professionals, patients' significant others, or a combination. We identified five main topics: decisions on disease-modifying drugs, decisions on chronic cerebrospinal venous insufficiency treatment, information provision and patient education, health literacy, and risk knowledge. CONCLUSIONS: The high proportion of included studies on SDM in MS in Europe suggests an earlier adoption of these concepts in this area. Decisions on disease-modifying drugs was the prevalent topic. Only 5% of studies were RCTs, indicating that more research is needed to study the effectiveness of SDM interventions. Studies addressing people with primary and secondary progressive MS are also needed.

Quantifying muscle fatigue during walking in people with multiple sclerosis.

BACKGROUND: This study aimed to examine muscle fatigue in lower leg muscles in of people with multiple sclerosis and healthy controls, and whether muscle fatigue coincided with potential changes in gait. METHODS: In this case-control study, people with multiple sclerosis (n = 8; 3male; mean age (SD) = 49.7 (9.6) yr) and age-matched healthy controls (n = 10; 4male; mean age (SD) = 47.4 (8.7) yr) walked on a treadmill for 12-min at self-paced speed. Muscle fatigue was indirectly quantified by a decrease in median frequency and increase in root mean square of surface electromyographic recordings of lower leg muscles. Walking speed, ankle push-off power and net ankle work were calculated from marker positions and force plate data using inverse dynamic calculations. RESULTS: People with multiple sclerosis showed larger decreases in median frequency of soleus (most affected leg: p = 0.003; least affected leg: p = 0.009) and larger increases in root mean square of soleus (most and least affected leg: p = 0.037), gastrocnemius medialis (most affected leg: p = 0.003; least affected leg: p = 0.005) and lateralis (most and least affected leg: p < 0.001) compared to controls. Walking speed (p = 0.001), ankle push-off power (most affected leg: p = 0.018; least affected leg: p = 0.001) and net work around the ankle (most affected leg: p = 0.046; least affected leg: p = 0.001) were lower in people with multiple sclerosis compared to controls, but increased in both groups. INTERPRETATION: The results yield preliminary evidence that soleus muscles of people with multiple sclerosis fatigue during prolonged walking. Changes in electromyography of gastrocnemius muscles could however be related to muscle fatigue, changes in gait or a combination.