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.

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.

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.

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.

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.

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.

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.

A qualitative study investigating the meaning of participation to improve the measurement of this construct.

PURPOSE: The purpose of this study was to improve the measurement of participation. Research questions were as follows: (1) What constitutes participation according to adults? (2) Do they mention participation subdomains that are not covered in the Patient-Reported Outcomes Measurement Information System (PROMIS) item bank "Ability to Participate in Social Roles and Activities"? METHODS: Semi-structured interviews were conducted with 46 adults from the general population. Interviews were thematically analysed using the International Classification of Functioning, Disability and Health (ICF) as conceptual framework. Thereafter, assigned codes were compared to PROMIS item bank. RESULTS: Participants mentioned a variety of participation subdomains that were meaningful to them, such as socializing and employment. All subdomains could be classified into the ICF. The following subdomains were not covered by the PROMIS item bank: acquisition of necessities, education life, economic life, community life, and religion and spirituality. Also a distinction between remunerative (i.e. paid) and non-remunerative (i.e. unpaid) employment, and domestic life was missing. Several ICF sub-codes were not mentioned, such as ceremonies. CONCLUSIONS: Many participation subdomains were mentioned to be meaningful. As several of these subdomains are not covered in the PROMIS item bank, it may benefit from extension with new (patient-)reported subdomains of participation.

The Transmural Trauma Care Model (TTCM) for the rehabilitation of trauma patients is effective in improving patient related outcome measures: a non-randomized controlled trial.

BACKGROUND: The Transmural Trauma Care Model (TTCM) is a refined post-clinical rehabilitation approach, in which a multidisciplinary hospital-based team guides a network of primary care physical therapists in the treatment of trauma patients. The objective of this study was to assess the effectiveness of the TTCM compared to regular care. METHODS: A controlled-before-and-after study was performed in a level 1 trauma center. The TTCM includes four elements: 1) a multidisciplinary team at the outpatient clinic, 2) coordination and individual goal setting for each patient by this team, 3) a network of primary care physical therapists, 4) E-health support for transmural communication. Intervention group patients were prospectively followed (3, 6 and 9 months). The control group consisted of 4 clusters of patients who either had their first consultation at the outpatient clinic 0, 3, 6 or 9 months ago. Outcomes included generic- and disease-specific health-related quality of life (HR-QOL), pain, functional status, patient satisfaction, and perceived recovery. Between-group comparisons were made using linear regression analyses. The recovery pattern of intervention group patients was identified using longitudinal data analysis methods. RESULTS: A total of 83 participants were included in the intervention group. In the control group, 202 participants were included (68 in the baseline cluster, 26 in the 3-month cluster, 51 in the 6-month cluster, 57 in the 9-month cluster). Between-group differences were statistically significant in favor of the intervention group for disease-specific HR-QOL at 9 months, pain at 6 and 9 months, functional status at 6 and 9 months, patient satisfaction at 3, 6 and 9 months, and perceived recovery at 6 months. No significant differences were found between groups for generic HR-QOL at any time point. Generic HR-QOL, disease-specific HR-QOL, pain, and functional status significantly improved in a linear fashion among intervention group patients during the nine-month follow-up period. CONCLUSIONS: This study provides preliminary evidence that the TTCM is effective in improving patient related outcome measures, such as disease-specific HR-QOL, pain and functional status. A multicenter, and ideally randomized controlled trial, is required to confirm these results. TRIAL REGISTRATION: The trial is registered at the Dutch Trial Register (NTR5474). Registered 12 October 2015. Retrospectively registered.

Energy Conservation Management for People With Multiple Sclerosis-Related Fatigue: Who Benefits?

OBJECTIVE: We investigated whether demographic, disease-related, or personal baseline determinants can predict a positive response to energy conservation management (ECM). METHOD: We conducted a secondary analysis of a single-blind, two-parallel-arms randomized controlled trial that included ambulatory adults with severe MS-related fatigue. Therapy responders and nonresponders were categorized by Checklist Individual Strength fatigue change scores between baseline and end of treatment. Logistic regression analyses were used to assess the determinants of response. RESULTS: Sixty-nine participants were included (ECM group, n = 34; control group, n = 35). In the ECM group, fatigue severity, perception of fatigue, illness cognitions about MS, and social support discrepancies were related to the probability of being a responder. CONCLUSION: The results suggest that people with MS-related fatigue who had a less negative perception of fatigue and who perceived fewer disease benefits and a higher discrepancy in social support had the best response to ECM treatment.

Effectiveness of energy conservation management on fatigue and participation in multiple sclerosis: A randomized controlled trial.

BACKGROUND: Fatigue is a frequently reported and disabling symptom in multiple sclerosis (MS). OBJECTIVE: To investigate the effectiveness of an individual energy conservation management (ECM) intervention on fatigue and participation in persons with primary MS-related fatigue. METHODS: A total of 86 severely fatigued and ambulatory adults with a definite diagnosis of MS were randomized in a single-blind, two-parallel-arm randomized clinical trial to the ECM group or the information-only control group in outpatient rehabilitation departments. Blinded assessments were carried out at baseline and at 8, 16, 26 and 52 weeks after randomization. Primary outcomes were fatigue (fatigue subscale of Checklist Individual Strength - CIS20r) and participation (Impact on Participation and Autonomy scale - IPA). RESULTS: Modified intention-to-treat analysis was based on 76 randomized patients (ECM, n = 36; MS nurse, n=40). No significant ECM effects were found for fatigue (overall difference CIS20r between the groups = -0.81; 95% confidence interval (CI), -3.71 to 2.11) or for four out of five IPA domains. An overall unfavourable effect was found in the ECM group for the IPA domain social relations (difference between the groups = 0.19; 95% CI, 0.03 to 0.35). CONCLUSION: The individual ECM format used in this study did not reduce MS-related fatigue and restrictions in participation more than an information-only control condition.

Does aerobic training alleviate fatigue and improve societal participation in patients with multiple sclerosis? A randomized controlled trial.

BACKGROUND: Evidence supporting the effectiveness of aerobic training, specific for fatigue, in severely fatigued patients with multiple sclerosis (MS) is lacking. OBJECTIVE: To estimate the effectiveness of aerobic training on MS-related fatigue and societal participation in ambulant patients with severe MS-related fatigue. METHODS: Patients ( N = 90) with severe MS-related fatigue were allocated to 16-week aerobic training or control intervention. Primary outcomes were perceived fatigue (Checklist Individual Strength (CIS20r) fatigue subscale) and societal participation. An improvement of ⩾8 points on the CIS20r fatigue subscale was considered clinically relevant. Outcomes were assessed by a blinded observer at baseline, 2, 4, 6 and 12 months. RESULTS: Of the 89 patients that started treatment (median Expanded Disability Status Scale (interquartile range), 3.0 (2.0-3.6); mean CIS20r fatigue subscale (standard deviation (SD)), 42.6 (8.0)), 43 received aerobic training and 46 received the control intervention. A significant post-intervention between-group mean difference (MD) on the CIS20r fatigue subscale of 4.708 (95% confidence interval (CI) = 1.003-8.412; p = 0.014) points was found in favour of aerobic training that, however, was not sustained during follow-up. No effect was found on societal participation. CONCLUSION: Aerobic training in MS patients with severe fatigue does not lead to a clinically meaningful reduction in fatigue or societal participation when compared to a low-intensity control intervention.

Cognitive behavioral therapy positively affects fatigue in patients with multiple sclerosis: Results of a randomized controlled trial.

BACKGROUND: Fatigue is a common symptom in multiple sclerosis (MS) and often restricts societal participation. Cognitive behavioral therapy (CBT) may alleviate MS-related fatigue, but evidence in literature is inconclusive. OBJECTIVE: To evaluate the effectiveness of CBT to improve MS-related fatigue and participation. METHODS: In a multi-center, assessor-masked, randomized controlled trial, participants with severe MS-related fatigue were assigned to CBT or control treatment. CBT consisted of 12 individual sessions with a psychologist trained in CBT, the control treatment consisted of three consultations with a MS nurse, both delivered over 16 weeks. Assessments were at baseline, 8, 16 (i.e. post-intervention), 26, and 52 weeks post-baseline. Primary outcomes were the Checklist Individual Strength-fatigue subscale (CIS20r fatigue) and the Impact on Participation and Autonomy questionnaire (IPA). Data were analyzed according to the intention-to-treat principle, using mixed-model analysis. RESULTS: Between 2011 and 2014, 91 patients were randomized (CBT: n = 44; control: n = 47). Between-group analysis showed a positive post-intervention effect for CBT on CIS20r fatigue (T16: -6.7 (95% confidence interval (CI) = -10.7; -2.7) points) that diminished during follow-up (T52: 0.5 (95% CI = -3.6; 4.4)). No clinically relevant effects were found on societal participation. CONCLUSION: Severe MS-related fatigue can be reduced effectively with CBT in the short term. More research is needed on how to maintain this effect over the long term.

The role of appraisal and coping style in relation with societal participation in fatigued patients with multiple sclerosis: a cross-sectional multiple mediator analysis.

To determine the relationship between appraisal and societal participation in fatigued patients with Multiple Sclerosis (MS), and whether this relation is mediated by coping styles. 265 severely-fatigued MS patients. Appraisal, a latent construct, was created from the General Self-Efficacy Scale and the helplessness and acceptance subscales of the Illness Cognition Questionnaire. Coping styles were assessed using the Coping Inventory Stressful Situations (CISS21) and societal participation was assessed using the Impact on Participation and Autonomy. A multiple mediator model was developed and tested by structural equation modeling on cross-sectional data. We corrected for confounding by disease-related factors. Mediation was determined using a product-of-coefficients approach. A significant relationship existed between appraisal and participation (ß = 0.21, 95 % CI 0.04-0.39). The pathways via coping styles were not significant. In patients with severe MS-related fatigue, appraisal and societal participation show a positive relationship that is not mediated by coping styles.

Feasibility and Safety of Cardiopulmonary Exercise Testing in Multiple Sclerosis: A Systematic Review.

OBJECTIVE: To investigate the feasibility and safety of cardiopulmonary exercise testing (CPET) in patients with multiple sclerosis (MS). DATA SOURCES: PubMed, EMBASE, CINAHL, SPORTDiscus, PsycINFO, ERIC, and the Psychology and Behavioral Sciences Collection were searched up to October 2014. References from retrieved articles were examined to identify additional relevant studies. STUDY SELECTION: Inclusion of original studies was on the basis of performance of maximal CPET, description of the protocol, and participants with definite MS aged ≥18 years. No language restrictions were applied. DATA EXTRACTION: The quality of CPET reporting in included studies was scored according to a structured checklist considering 10 feasibility (eg, test abnormalities) and 12 safety quality criteria (eg, adverse events). Structured data extraction was performed for these feasibility and safety features of CPET. DATA SYNTHESIS: Forty-six studies were included, comprising 1483 patients with MS, with a mean age ± SD of 42.0±5.8 years and a median Expanded Disability Status Scale (EDSS) score of 2.8 (first quartile=2.1; third quartile=3.9; range of average EDSS scores, .75-5.8). Quality of reporting on CPET varied from 3 to 13 out of a possible 22 quality points. The percentage of test abnormalities (feasibility) was 10.0%, primarily because of an inability to maintain pedaling at a specific resistance. The percentage of adverse events (safety) was 2.1%. All adverse events were temporary. CONCLUSIONS: Based on the available data, we conclude that CPET is feasible provided that the CPET modality is tailored to the physical abilities of the patient. Furthermore, CPET is safe when recommended precautions and safety measures are implemented. However, future optimization of CPET will require protocolized testing and the implementation of standard reporting procedures.

Is physical behavior affected in fatigued persons with multiple sclerosis?

OBJECTIVE: To study physical behavior in detail in fatigued persons with multiple sclerosis (MS). DESIGN: Case-control explorative study. SETTING: Outpatient rehabilitation department and participants' daily environment. PARTICIPANTS: Fatigued persons with MS (n=23) were selected from a randomized controlled trial. Cases were matched by age and sex to healthy, nonfatigued controls (n=23). Eligible persons with MS were severely fatigued (Checklist Individual Strength fatigue domain mean score, 43.2±6.6) and ambulatory (Expanded Disability Status Scale mean score, 2.5±1.5). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Measurements were performed using an accelerometer over 7 days. Outcomes included the following: amount of physical activity expressed in counts per day, counts per minute (CPM), and counts per day period (morning, afternoon, evening); duration of activity intensity categories (sedentary, light physical activity, moderate-to-vigorous physical activity [MVPA]); and distribution of MVPA and sedentary periods over the day. RESULTS: Persons with MS had fewer counts per day (mean difference, -156×10(3); 95% confidence interval [CI], -273×10(3) to -39×10(3); P=.010), had fewer CPM (mean difference, -135; 95% CI, -256 to -14; P=.030), and were less physically active in the morning (mean difference, -200; 95% CI, -389 to -11; P=.039) and evening (mean difference, -175; 95% CI, -336 to -14; P=.034) than controls. Persons with MS spent a higher percentage of their time sedentary (mean difference, 5.6; 95% CI, .1-11.1; P=.045) and spent less time at the higher MVPA intensity (mean difference, -2.4; 95% CI, -4.7 to -0.09; P=.042). They had fewer MVPA periods (mean difference, 29; 95% CI, -56.2 to -2.6; P=.032) and a different distribution of sedentary (mean difference, .033; 95% CI, .002 to .064; P=.039) and MVPA periods (mean difference, -.08; 95% CI, -.15 to -.01; P=.023). CONCLUSIONS: Detailed analyses of physical behavior showed that ambulatory fatigued persons with MS do differ from healthy controls not only in physical activity level, but also in other physical behavior dimensions (eg, day patterns, intensity, distribution).

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.

Challenges in multi-plex and mono-plex platforms for the discovery of inflammatory profiles in neurodegenerative diseases.

Pro and anti-inflammatory cytokines are involved in disease onset and pathophysiology of multiple sclerosis, Alzheimer's disease and Parkinson's disease. It is likely that panels of multiple cytokines provide a good reflection of disease status and can be used as biological markers in body fluids. Different multi-plex platforms, Luminex-xMAP and Meso Scale Discovery, are able to detect multiple analytes in the same sample at the same time. In this literature based review, we offer an overview of the multi-plex platforms and compare them with the golden standard ELISA in their ability to accurately and sensitively detect cytokines in cerebrospinal fluid (CSF) and blood (serum/plasma). The detectability and levels of cytokines in multiple sclerosis, Alzheimer's disease and Parkinson's disease are promising but also show discrepancies between studies. The current immuno-assays lack sensitivity for detection of various cytokines that have low concentrations of cytokines in CSF and blood, and therefore technical improvements are needed. With such improvements the use of large panels of cytokines as inflammatory profiles may offer additional value in diagnosis, prognosis and therapeutic response in neurodegenerative diseases.