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.
Abstract Background Fatigue is a frequently occurring symptom of multiple sclerosis (MS) that limits social participation. Objective To systematically determine the short and long-term effects of ...cognitive behavioral therapy (CBT) for the treatment of MS-related fatigue. Data sources Pubmed, Cochrane, EMBASE, Psychology and Behavioral Sciences Collection, ERIC, PsychINFO, Cinahl, PsycARTICLES, and relevant trial registers were searched up to February 2016. In addition, references from retrieved articles were examined. Study selection Studies were included if participants had MS, fatigue was a primary outcome measure, the intervention was CBT, and the design was a randomized controlled trial. The search was performed by two independent reviewers, three CBT experts determined whether interventions were CBT. Data extraction Data on patient and study characteristics and fatigue were systematically extracted using a standardized data extraction form. Two independent reviewers assessed risk of bias using the Cochrane Collaboration risk of bias tool. In the event of disagreement, a third reviewer was consulted. Data synthesis Of the 994 identified studies, 4 studies were included in the meta-analysis, comprising 193 CBT-treated patients and 210 patients who underwent a control treatment. Meta-analyses of these studies showed that CBT treatment had a positive short-term effect on fatigue (standardized mean difference SMD = − 0.47; 95% confidence interval CI = − 0.88;
− 0.06; I2 = 73%). In addition, three studies showed a long-term positive effect of CBT (SMD = − 0.30; CI
− 0.51;
− 0.08; I2 = 0%). Conclusions This review found that the use of CBT for the treatment of fatigue in patients with MS has a moderately positive short-term effect. However, this effect decreases with cessation of treatment.
Changes in scores on health status questionnaires are difficult to interpret. Several methods to determine minimally important changes (MICs) have been proposed which can broadly be divided in ...distribution-based and anchor-based methods. Comparisons of these methods have led to insight into essential differences between these approaches. Some authors have tried to come to a uniform measure for the MIC, such as 0.5 standard deviation and the value of one standard error of measurement (SEM). Others have emphasized the diversity of MIC values, depending on the type of anchor, the definition of minimal importance on the anchor, and characteristics of the disease under study. A closer look makes clear that some distribution-based methods have been merely focused on minimally detectable changes. For assessing minimally important changes, anchor-based methods are preferred, as they include a definition of what is minimally important. Acknowledging the distinction between minimally detectable and minimally important changes is useful, not only to avoid confusion among MIC methods, but also to gain information on two important benchmarks on the scale of a health status measurement instrument. Appreciating the distinction, it becomes possible to judge whether the minimally detectable change of a measurement instrument is sufficiently small to detect minimally important changes.
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.
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
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.
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 (β -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 (β -0.80, 95%CI -0.92; -0.68). Higher fatigue levels resulted in higher perceived strain (all societal participation domains) (β 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.
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.
To examine the energy demand of walking relative to aerobic capacity in people with multiple sclerosis.
Cross-sectional cohort study.
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).
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.
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.
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.
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.
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).
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.
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.
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