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.

Respiratory muscle training for multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic disease of the central nervous system, affecting approximately 2.5 million people worldwide. People with MS may experience limitations in muscular strength and endurance - including the respiratory muscles, affecting functional performance and exercise capacity. Respiratory muscle weakness can also lead to diminished performance on coughing, which may result in (aspiration) pneumonia or even acute ventilatory failure, complications that frequently cause death in MS. Training of the respiratory muscles might improve respiratory function and cough efficacy. OBJECTIVES: To assess the effects of respiratory muscle training versus any other type of training or no training for respiratory muscle function, pulmonary function and clinical outcomes in people with MS. SEARCH METHODS: We searched the Trials Register of the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group (3 February 2017), which contains trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, LILACS and the trial registry databases ClinicalTrials.gov and WHO International Clinical Trials Registry Platform. Two authors independently screened records yielded by the search, handsearched reference lists of review articles and primary studies, checked trial registers for protocols, and contacted experts in the field to identify further published or unpublished trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that investigated the efficacy of respiratory muscle training versus any control in people with MS. DATA COLLECTION AND ANALYSIS: One reviewer extracted study characteristics and study data from included RCTs, and two other reviewers independently cross-checked all extracted data. Two review authors independently assessed risk of bias with the Cochrane 'Risk of bias' assessment tool. When at least two RCTs provided data for the same type of outcome, we performed meta-analyses. We assessed the certainty of the evidence according to the GRADE approach. MAIN RESULTS: We included six RCTs, comprising 195 participants with MS. Two RCTs investigated inspiratory muscle training with a threshold device; three RCTs, expiratory muscle training with a threshold device; and one RCT, regular breathing exercises. Eighteen participants (˜ 10%) dropped out; trials reported no serious adverse events.We pooled and analyzed data of 5 trials (N=137) for both inspiratory and expiratory muscle training, using a fixed-effect model for all but one outcome. Compared to no active control, meta-analysis showed that inspiratory muscle training resulted in no significant difference in maximal inspiratory pressure (mean difference (MD) 6.50 cmH2O, 95% confidence interval (CI) -7.39 to 20.38, P = 0.36, I2 = 0%) or maximal expiratory pressure (MD -8.22 cmH2O, 95% CI -26.20 to 9.77, P = 0.37, I2 = 0%), but there was a significant benefit on the predicted maximal inspiratory pressure (MD 20.92 cmH2O, 95% CI 6.03 to 35.81, P = 0.006, I2 = 18%). Meta-analysis with a random-effects model failed to show a significant difference in predicted maximal expiratory pressure (MD 5.86 cmH2O, 95% CI -10.63 to 22.35, P = 0.49, I2 = 55%). These studies did not report outcomes for health-related quality of life.Three RCTS compared expiratory muscle training versus no active control or sham training. Under a fixed-effect model, meta-analysis failed to show a significant difference between groups with regard to maximal expiratory pressure (MD 8.33 cmH2O, 95% CI -0.93 to 17.59, P = 0.18, I2 = 42%) or maximal inspiratory pressure (MD 3.54 cmH2O, 95% CI -5.04 to 12.12, P = 0.42, I2 = 41%). One trial assessed quality of life, finding no differences between groups.For all predetermined secondary outcomes, such as forced expiratory volume, forced vital capacity and peak flow pooling was not possible. However, two trials on inspiratory muscle training assessed fatigue using the Fatigue Severity Scale (range of scores 0-56 ), finding no difference between groups (MD, -0.28 points, 95% CI-0.95 to 0.39, P = 0.42, I2 = 0%). Due to the low number of studies included, we could not perform cumulative meta-analysis or subgroup analyses. It was not possible to perform a meta-analysis for adverse events, no serious adverse were mentioned in any of the included trials.The quality of evidence was low for all outcomes because of limitations in design and implementation as well as imprecision of results. AUTHORS' CONCLUSIONS: This review provides low-quality evidence that resistive inspiratory muscle training with a resistive threshold device is moderately effective postintervention for improving predicted maximal inspiratory pressure in people with mild to moderate MS, whereas expiratory muscle training showed no significant effects. The sustainability of the favourable effect of inspiratory muscle training is unclear, as is the impact of the observed effects on quality of life.

Exercise therapy for fatigue in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system affecting an estimated 1.3 million people worldwide. It is characterised by a variety of disabling symptoms of which excessive fatigue is the most frequent. Fatigue is often reported as the most invalidating symptom in people with MS. Various mechanisms directly and indirectly related to the disease and physical inactivity have been proposed to contribute to the degree of fatigue. Exercise therapy can induce physiological and psychological changes that may counter these mechanisms and reduce fatigue in MS. OBJECTIVES: To determine the effectiveness and safety of exercise therapy compared to a no-exercise control condition or another intervention on fatigue, measured with self-reported questionnaires, of people with MS. SEARCH METHODS: We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Trials Specialised Register, which, among other sources, contains trials from: the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 10), MEDLINE (from 1966 to October 2014), EMBASE (from 1974 to October 2014), CINAHL (from 1981 to October 2014), LILACS (from 1982 to October 2014), PEDro (from 1999 to October 2014), and Clinical trials registries (October 2014). Two review authors independently screened the reference lists of identified trials and related reviews. SELECTION CRITERIA: We included randomized controlled trials (RCTs) evaluating the efficacy of exercise therapy compared to no exercise therapy or other interventions for adults with MS that included subjective fatigue as an outcome. In these trials, fatigue should have been measured using questionnaires that primarily assessed fatigue or sub-scales of questionnaires that measured fatigue or sub-scales of questionnaires not primarily designed for the assessment of fatigue but explicitly used as such. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the articles, extracted data, and determined methodological quality of the included trials. Methodological quality was determined by means of the Cochrane 'risk of bias' tool and the PEDro scale. The combined body of evidence was summarised using the GRADE approach. The results were aggregated using meta-analysis for those trials that provided sufficient data to do so. MAIN RESULTS: Forty-five trials, studying 69 exercise interventions, were eligible for this review, including 2250 people with MS. The prescribed exercise interventions were categorised as endurance training (23 interventions), muscle power training (nine interventions), task-oriented training (five interventions), mixed training (15 interventions), or 'other' (e.g. yoga; 17 interventions). Thirty-six included trials (1603 participants) provided sufficient data on the outcome of fatigue for meta-analysis. In general, exercise interventions were studied in mostly participants with the relapsing-remitting MS phenotype, and with an Expanded Disability Status Scale less than 6.0. Based on 26 trials that used a non-exercise control, we found a significant effect on fatigue in favour of exercise therapy (standardized mean difference (SMD) -0.53, 95% confidence interval (CI) -0.73 to -0.33; P value < 0.01). However, there was significant heterogeneity between trials (I(2) > 58%). The mean methodological quality, as well as the combined body of evidence, was moderate. When considering the different types of exercise therapy, we found a significant effect on fatigue in favour of exercise therapy compared to no exercise for endurance training (SMDfixed effect -0.43, 95% CI -0.69 to -0.17; P value < 0.01), mixed training (SMDrandom effect -0.73, 95% CI -1.23 to -0.23; P value < 0.01), and 'other' training (SMDfixed effect -0.54, 95% CI -0.79 to -0.29; P value < 0.01). Across all studies, one fall was reported. Given the number of MS relapses reported for the exercise condition (N = 25) and non-exercise control condition (N = 26), exercise does not seem to be associated with a significant risk of a MS relapse. However, in general, MS relapses were defined and reported poorly. AUTHORS' CONCLUSIONS: Exercise therapy can be prescribed in people with MS without harm. Exercise therapy, and particularly endurance, mixed, or 'other' training, may reduce self reported fatigue. However, there are still some important methodological issues to overcome. Unfortunately, most trials did not explicitly include people who experienced fatigue, did not target the therapy on fatigue specifically, and did not use a validated measure of fatigue as the primary measurement of outcome.

Measurement properties of the Dutch version of the Western Ontario Shoulder Instability Index (WOSI).

BACKGROUND: The Western Ontario Shoulder Instability Index (WOSI) is a disease-specific shoulder questionnaire to measure quality of life in patients with shoulder instability. The aim of the present study was to translate the WOSI into Dutch and assess its principal measurement properties. METHODS: The WOSI was translated into Dutch according to guidelines in the literature. Fifty-two shoulder instability patients completed the questionnaire twice within 2 weeks. We assessed internal consistency (Cronbach's alpha), test-retest reliability [Intraclass Correlation Coefficient (ICC)], standard error of measurement (SEM), smallest detectable change (SDC) and reliable change index. The Bland-Altman analysis was applied to assess test-retest agreement and floor and ceiling effects were calculated. RESULTS: Cronbach's alpha was 0.95 for the total WOSI score (range 0.88-0.95 for the 4 domains). ICC for the total WOSI score was 0.91 (range 0.79-0.90 for domains), SEM was 130.6 for the total WOSI score resulting in a SDC of 362.0, which is 17.3 % of the maximum obtainable score of 2100. Bland-Altman analysis showed no systematic differences or consistent bias between the two assessments. We observed no relevant floor and ceiling effects. CONCLUSION: The results of the present study suggest the Dutch version of the WOSI is a reliable tool for clinical assessment and scientific evaluation. It shows high values for Cronbach's alpha and ICC implying excellent internal consistency and good test-retest reliability.

Validation of a Dutch version of the Neurological Fatigue Index (NFI-MS) for patients with multiple sclerosis in the Netherlands.

PURPOSE: Fatigue is a complex, multidimensional construct. Most questionnaires measuring fatigue do not meet the standards for good measurement properties. Therefore, the Neurological Fatigue Index for multiple sclerosis (NFI-MS) is recently developed using thorough methods. The aim of this study was to develop and validate the Dutch version of the NFI-MS. METHODS: The original English version of the NFI-MS was translated into Dutch using a forward-backward procedure. Reliability (intraclass correlation coefficient (ICC) and standard error of measurement (SEM)) were assessed for the summary score and the four subscale scores separately. Construct validity was assessed by testing hypotheses about expected correlations between the NFI-MS and other constructs (e.g. impact on functioning and depression) and expected differences on NFI scores between groups defined on the basis of disease type and work status. RESULTS: The reliability analyses (n = 118) showed that the ICC was 0.78 (NFI-MS summary) and ranged from 0.75 to 0.83 for the four subscales and the SEM was 2.5 (NFI-MS summary) and ranged from 1.1 to 2.2 for the four subscales. For construct validity (n = 136), 50 out of the 57 expected hypotheses were confirmed (88 %). CONCLUSION: The present study shows that the Dutch version of the NFI-MS is a reliable and valid self-report questionnaire for measuring fatigue in Dutch patients with MS.

Reproducibility of the Dutch version of the Western Ontario rotator cuff Index.

BACKGROUND: The Western Ontario Rotator Cuff Index (WORC) is a disease-specific shoulder questionnaire, originally developed at the University of Western Ontario, to measure quality of life in patients with rotator cuff disease (RCD). The aim of the present study was to cross-culturally adapt the WORC for use in the Netherlands and to evaluate the reproducibility in patients with RCD. MATERIALS AND METHODS: The WORC was translated into Dutch according to leading guidelines in the literature, and 52 patients with RCD completed the questionnaire twice within 2 weeks. The Cronbachs α and the intraclass correlation coefficient (ICC) were calculated, Bland-Altman analysis was applied, and the smallest detectable change (SDC) and reliable change index (RCI) were determined. RESULTS: The Cronbachs α ranged from 0.91 to 0.97 for the total WORC score and for the 5 domains. High ICCs were found for the WORC total score (0.94) and for the separate domains (range, 0.85-0.91). Bland-Altman analyses showed no systematic differences between assessments. SDC was 355.7 for the total WORC score, varying from 80.4 to 148.0 for the domains, resulting in RCIs of 16.9% for the total WORC score and 24.7% to 30.2% for the domains. CONCLUSIONS: The results of the present study suggest good reproducibility of the Dutch version of the WORC in Dutch-speaking patients with RCD. Additional research on the validation of the Dutch version of the WORC is required in the near future.

(HIIT-The Track) High-Intensity Interval Training for People with Parkinson's Disease: Individual Response Patterns of (Non-)Motor Symptoms and Blood-Based Biomarkers-A Crossover Single-Case Experimental Design.

INTRODUCTION: Physical exercise is receiving increasing interest as an augmentative non-pharmacological intervention in Parkinson's disease (PD). This pilot study primarily aimed to quantify individual response patterns of motor symptoms to alternating exercise modalities, along with non-motor functioning and blood biomarkers of neuroplasticity and neurodegeneration. MATERIALS & METHODS: People with PD performed high-intensity interval training (HIIT) and continuous aerobic exercise (CAE) using a crossover single-case experimental design. A repeated assessment of outcome measures was conducted. The trajectories of outcome measures were visualized in time series plots and interpreted relative to the minimal clinically important difference (MCID) and smallest detectable change (SDC) or as a change in the positive or negative direction using trend lines. RESULTS: Data of three participants were analyzed and engaging in physical exercise seemed beneficial for reducing motor symptoms. Participant 1 demonstrated improvement in motor function, independent of exercise modality; while for participant 2, such a clinically relevant (positive) change in motor function was only observed in response to CAE. Participant 3 showed improved motor function after HIIT, but no comparison could be made with CAE because of drop-out. Heterogeneous responses on secondary outcome measures were found, not only between exercise modalities but also among participants. CONCLUSION: Though this study underpins the positive impact of physical exercise in the management of PD, large variability in individual response patterns to the interventions among participants makes it difficult to identify clear exercise-induced adaptations in functioning and blood biomarkers. Further research is needed to overcome methodological challenges in measuring individual response patterns.

Self-report fatigue questionnaires in multiple sclerosis, Parkinson's disease and stroke: a systematic review of measurement properties.

PURPOSE: To critically appraise, compare and summarize the measurement properties of self-report fatigue questionnaires validated in patients with multiple sclerosis (MS), Parkinson's disease (PD) or stroke. METHODS: MEDLINE, EMBASE, PsycINFO, CINAHL and SPORTdiscus were searched. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to assess the methodological quality of studies. A qualitative data synthesis was performed to rate the measurement properties for each questionnaire. RESULTS: Thirty-eight studies out of 5,336 records met the inclusion criteria, evaluating 31 questionnaires. Moderate evidence was found for adequate internal consistency and structural validity of the Fatigue Scale for Motor and Cognitive functions (FSMC) and for adequate reliability and structural validity of the Unidimensional Fatigue Impact Scale (U-FIS) in MS. CONCLUSIONS: We recommend the FSMC and U-FIS in MS. The Functional Assessment of Chronic Illness Therapy Fatigue subscale (FACIT-F) and Fatigue Severity Scale (FSS) show promise in PD, and the Profile of Mood States Fatigue subscale (POMS-F) for stroke. Future studies should focus on measurement error, responsiveness and interpretability. Studies should also put emphasis on providing input for the theoretical construct of fatigue, allowing the development of questionnaires that reflect generic and disease-specific symptoms of fatigue.

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.

The association between perceived fatigue and actual level of physical activity in multiple sclerosis.

BACKGROUND: Both fatigue and reduced physical activity are important consequences of multiple sclerosis (MS). However, their mutual association is poorly understood. OBJECTIVE: The objective of the study was to determine the relation between perceived fatigue and home-based recording of motor activity in patients with MS. METHODS: Found associations were checked for confounding by age, Expanded Disability Status Scales (EDSS), disease duration, sub-type of MS, anxiety, and depression. Forty-three ambulatory patients with MS were recruited. Ambulatory physical activity was recorded for 24 hours. Fatigue was assessed with the Fatigue Severity Scale (FSS), the Modified Fatigue Impact Scale (MFIS) and the Checklist Individual Strength (CIS20R). Linear regression was applied after which potential confounding factors were introduced in a multivariate regression model. RESULTS: No significant associations between physical activity and fatigue scores were found, except for the MFIS sub-scale 'physical activity' (ß(physical_activity) [ß(pa)] = -0.044; SE = 0.020). The association between physical activity and the FSS score was distorted by age, MS-type, anxiety and depression and the association between physical activity and the MFIS score by age and depression. The inverse association between MFIS sub-scale 'physical activity' and physical activity was significantly strengthened by adjusting for age (ß(pa) = - 0.052; SE = 0.019), sub-type of MS (ß(pa) = - 0.048; SE = 0.020), anxiety (ß(pa) = - 0.070; SE = 0.023) and depression (ß(pa) = - 0.083; SE = 0.023). CONCLUSIONS: In MS, there is no, or at best a weak association between severity of perceived fatigue and physical activity. Depending on the fatigue questionnaire used, patient characteristics such as age, type of MS, depression and anxiety are factors that may affect this relationship.

How reproducible is home-based 24-hour ambulatory monitoring of motor activity in patients with multiple sclerosis?

OBJECTIVE: To determine the reproducibility of 24-hour monitoring of motor activity in patients with multiple sclerosis (MS). DESIGN: Test-retest design; 6 research assistants visited the participants twice within 1 week in the home situation. SETTING: General community. PARTICIPANTS: A convenience sample of ambulatory patients (N=43; mean age ± SD, 48.7±7.0y; 30 women; median Expanded Disability Status Scale scores, 3.5; interquartile range, 2.5) were recruited from the outpatient clinic of a university medical center. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Dynamic activity and static activity parameters were recorded by using a portable data logger and classified continuously for 24 hours. Reproducibility was determined by calculating intraclass correlation coefficients (ICCs) for test-retest reliability and by applying the Bland-Altman method for agreement between the 2 measurements. The smallest detectable change (SDC) was calculated based on the standard error of measurement. RESULTS: Test-retest reliability expressed by the ICC(agreement) was .72 for dynamic activity, .74 for transitions, .77 for walking, .71 for static activity, .67 for sitting, .62 for standing, and .55 for lying. Bland and Altman analysis indicated no systematic differences between the first and second assessment for dynamic and static activity. Measurement error expressed by the SDC was 1.23 for dynamic activity, 66 for transitions, .99 for walking, 1.52 for static activity, 4.68 for lying, 3.95 for sitting, and 3.34 for standing. CONCLUSIONS: The current study shows that with 24-hour monitoring, a reproducible estimate of physical activity can be obtained in ambulatory patients with MS.

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.

High-Intensity Interval Cycle Ergometer Training in Parkinson's Disease: Protocol for Identifying Individual Response Patterns Using a Single-Subject Research Design.

Background: People with Parkinson's disease (PD) experience not only motor problems but also non-motor problems that seriously impede their daily functioning and quality of life. The current pharmacologic treatment of PD is symptomatic, and alternative rehabilitation treatments, which preferably also have a disease-modifying effect and promote neuroplasticity, are needed. Recent studies suggest that high-intensity interval training (HIIT) is promising for promoting neuroplasticity in human PD, with short training time and reduced burden. Biomarkers for neuroplasticity such as brain-derived neurotrophic factor (BDNF) and neurodegeneration (including neurofilament NfL and α-synuclein) may play a role, but their response to HIIT is not well-investigated. Objectives: The aims of this study were (1) to study the effects of 4 weeks of HIIT compared with 4 weeks of continuous aerobic exercise on motor and non-motor outcomes of PD and (2) to investigate the association between HIIT, motor/non-motor performances changes, and blood biomarker levels for neuroplasticity and neurodegeneration. Study Design: Single-subject research design with alternating treatment setup (ABACA) and frequent repeated measurements was used. Each participant received different intervention conditions (B/C) interspersed with baseline periods (A, i.e., ABACA or ACABA), and frequent repeated assessment of outcome measures is done to quantify within-subject, individual response patterns with sufficient power for data analysis. Blood samples were collected once a week in the baseline and training phases (A1 and B/C) and once every 2 weeks in the washout phases (A2 and A3). Intervention: Four subjects with PD on stable dopaminergic medication, two in Hoehn-Yahr stage 1-2, and two in Hoehn-Yahr stage 2.5-3 followed an ABACA or ACABA schedule, consisting of blocks with 30-min sessions of "B" (HIIT) or 50-min sessions of "C" [continuous aerobic exercise (CAE)] 3×/week for 4 weeks, separated by baseline "A" periods of 8 weeks for a total duration of 28 weeks. Outcome Measures: Outcome measures include disease status [Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)], blood biomarkers (BDNF, Nfl, and α-synuclein), measures for functional mobility (including an activity tracker), and activities of daily living, as well as cognition, mood, biorhythm (sleeping problems), and quality of life. Data Analysis: Visual analysis of trends in level, slope, and variability in response patterns was carried out, confirmed by longitudinal regression analysis with phase (ABACA) as the independent variable.

Feasibility of a Home-Based Tablet App for Dexterity Training in Multiple Sclerosis: Usability Study.

BACKGROUND: Persons with multiple sclerosis (MS) often experience dexterous difficulties during the performance of activities of daily living, such as fastening buttons, handling coins, or writing, therefore impacting their health-related quality of life. Mobile health (mHealth) solutions, such as tablet apps, may be used to train impaired dexterous skills. The feasibility of a tablet app-based dexterity home-based intervention in MS (TAD-MS) has not been explored yet in persons with MS. OBJECTIVE: The aim of this pilot study was to evaluate the feasibility and usability of home-based dexterity training with a tablet app in both persons with MS and healthy subjects. METHODS: A total of 9 persons with MS, aged 35-71 years, with an Expanded Disability Status Scale score between 2 and 7.5, performed the TAD-MS for 4 weeks, five times a week, with each training session lasting approximately 30 minutes. Participants' impaired dexterity was measured by the Nine-Hole Peg Test. A total of 10 age-matched healthy subjects also tested and rated the usability of the app. Outcome measures were the adherence rate as well as usability measured by the System Usability Scale and a Custom User Engagement Questionnaire (CUEQ). RESULTS: High feasibility of the tablet app-based dexterity training program was shown by a 97% adherence rate to the training protocol (ie, mean 19.4/20 sessions completed, SD 0.8). High system usability scores (ie, mean 85.39%, SD 11.67) and overall high scores given in the CUEQ (ie, mean 8.2/10, SD 1.4) further point to high usability of the app. Neither demographic variables nor dexterity levels affected the use of the app. CONCLUSIONS: This pilot study is the first to demonstrate high feasibility and usability of a new tablet app-based dexterity home-based training program among both persons with MS and healthy individuals. Whether this kind of training improves dexterity will need to be evaluated in a randomized controlled trial.

Preliminary effectiveness of a sequential exercise intervention on gait function in ambulant patients with multiple sclerosis - A pilot study.

BACKGROUND: Patients with multiple sclerosis (pwMS) often experience a decline in motor function and performance during prolonged walking, which potentially is associated with reduced ankle push-off power and might be alleviated through structured exercise. The objectives of this pilot study were to assess ankle push-off power and walking performance in pwMS and healthy controls, and the preliminary effectiveness of a sequential exercise program (resistance training followed by walking-specific endurance training) on ankle push-off power and walking performance. METHODS: PwMS (N = 10) with self-reported reduced walking performance and healthy controls (N = 10; at baseline only) underwent 3D gait analysis during a self-paced 12-minute walking test to assess walking performance prior to and following a sequential exercise program. Secondary testing paradigms comprised isometric muscle testing (triceps surae), cardiopulmonary exercise testing and self-report measures. FINDINGS: PwMS had a shorter 12-minute walking distance, and lower peak ankle push-off power (most-affected leg) in comparison to healthy controls. There was no minute-to-minute decline in walking performance. The 8-week resistance training significantly improved walking distance. In parallel, higher peak and speed-normalized ankle push-off power were found in the less-affected side. No additional changes were found following the walking-specific endurance training phase. INTERPRETATION: There was no walking-related motor fatigue found during a self-paced 12-minute walking test despite reduced ankle push-off power, and self-reported walking problems. Preliminary effects suggest a positive effect of resistance training on walking performance, potentially associated with increases in ankle push-off power, interestingly, in the less-affected leg. The added effect of the walking-specific endurance training remains unclear.

Tablet App Based Dexterity Training in Multiple Sclerosis (TAD-MS): Research Protocol of a Randomized Controlled Trial.

Introduction: Patients with Multiple Sclerosis exhibit disturbed dexterity, leading to difficulties in fine motor skills such as buttoning a T-shirt or hand-writing. Consequently, activities of daily living and quality of life are affected. The aim of the present study is to investigate the effectiveness of a tablet app-based home-based training intervention to improve dexterity in patients with Multiple Sclerosis. Methods: An observer-blinded randomized controlled trial will be performed. Seventy patients with Multiple Sclerosis with self-reported difficulties in dexterity while executing activities of daily living will be recruited. After baseline assessment, participants are randomized to either an intervention group (n = 35) or control group (n = 35) by a computerized procedure. Blinded assessments will be done at baseline, post-intervention (after 4 weeks) and 12 weeks follow-up. The home-based intervention consists of a 4-week tablet app-based dexterity program. The app contains six dexterity games in which finger coordination, tapping, pinch grip is required. The control group will receive a Thera-band training program focused on strengthening the upper limb. The primary outcome is the Arm function of Multiple Sclerosis Questionnaire, a measure of patient-reported activities of daily living related dexterity. Secondary outcomes are dexterous function, hand strength, and quality of life. Discussion: This study will evaluate the effects of tablet app-based training for dexterity in patients with Multiple Sclerosis. We hypothesize that a challenging app-based dexterity program will improve dexterity both in the short term and the long-term. The improved finger and hand functions are expected to generalize to improved activities of daily living and quality of life.

Design of the ExCersion-VCI study: The effect of aerobic exercise on cerebral perfusion in patients with vascular cognitive impairment.

There is evidence for a beneficial effect of aerobic exercise on cognition, but underlying mechanisms are unclear. In this study, we test the hypothesis that aerobic exercise increases cerebral blood flow (CBF) in patients with vascular cognitive impairment (VCI). This study is a multicenter single-blind randomized controlled trial among 80 patients with VCI. Most important inclusion criteria are a diagnosis of VCI with Mini-Mental State Examination ≥22 and Clinical Dementia Rating ≤0.5. Participants are randomized into an aerobic exercise group or a control group. The aerobic exercise program aims to improve cardiorespiratory fitness and takes 14 weeks, with a frequency of three times a week. Participants are provided with a bicycle ergometer at home. The control group receives two information meetings. Primary outcome measure is change in CBF. We expect this study to provide insight into the potential mechanism by which aerobic exercise improves hemodynamic status.

Consensus on Exercise Reporting Template (CERT): Modified Delphi Study.

BACKGROUND: Exercise interventions are often incompletely described in reports of clinical trials, hampering evaluation of results and replication and implementation into practice. OBJECTIVE: The aim of this study was to develop a standardized method for reporting exercise programs in clinical trials: the Consensus on Exercise Reporting Template (CERT). DESIGN AND METHODS: Using the EQUATOR Network's methodological framework, 137 exercise experts were invited to participate in a Delphi consensus study. A list of 41 items was identified from a meta-epidemiologic study of 73 systematic reviews of exercise. For each item, participants indicated agreement on an 11-point rating scale. Consensus for item inclusion was defined a priori as greater than 70% agreement of respondents rating an item 7 or above. Three sequential rounds of anonymous online questionnaires and a Delphi workshop were used. RESULTS: There were 57 (response rate=42%), 54 (response rate=95%), and 49 (response rate=91%) respondents to rounds 1 through 3, respectively, from 11 countries and a range of disciplines. In round 1, 2 items were excluded; 24 items reached consensus for inclusion (8 items accepted in original format), and 16 items were revised in response to participant suggestions. Of 14 items in round 2, 3 were excluded, 11 reached consensus for inclusion (4 items accepted in original format), and 7 were reworded. Sixteen items were included in round 3, and all items reached greater than 70% consensus for inclusion. LIMITATIONS: The views of included Delphi panelists may differ from those of experts who declined participation and may not fully represent the views of all exercise experts. CONCLUSIONS: The CERT, a 16-item checklist developed by an international panel of exercise experts, is designed to improve the reporting of exercise programs in all evaluative study designs and contains 7 categories: materials, provider, delivery, location, dosage, tailoring, and compliance. The CERT will encourage transparency, improve trial interpretation and replication, and facilitate implementation of effective exercise interventions into practice.

Effects of multidisciplinary rehabilitation on chronic fatigue in multiple sclerosis: a randomized controlled trial.

BACKGROUND: Several rehabilitation programmes aim at reducing the impact of fatigue in MS patients. Acute and chronic fatigue should require different management. OBJECTIVES: To assess the effects of individually tailored, multidisciplinary outpatient rehabilitation (MDR) on chronic fatigue. METHODS: Forty-eight ambulatory MS patients with chronic fatigue were randomized to MDR or to MS-nurse consultation. Fatigue was assessed by the Checklist Individual Strength (CIS-20R). Secondary outcomes included the Modified Fatigue Impact Scale, Fatigue Severity Scale, Functional Independence Measure, Disability and Impact Profile (DIP), Multiple Sclerosis Impact Scale and the Impact on Participation and Autonomy (IPA). RESULTS: The primary outcome measure CIS-20R overall score showed no significant differences between groups at 12 weeks (P = 0.39) and 24 weeks follow-up (P = 0.14), nor for subscales (t = 12 and t = 24, 0.19≤P≤0.88). No significant within-group effects were found for both groups with respect to the primary (0.57≤p≤0.97) and secondary (0.11≤p≤0.92) outcome measures from baseline to 12 or 24 weeks. CONCLUSION: Multidisciplinary rehabilitation was not more effective in terms of reducing self-reported fatigue in MS patients compared to MS-nurse consultation. Our results suggest that chronic fatigue in patients with MS may be highly invariant over time, irrespective of interventions. TRIAL REGISTRATION: controlled-trials.com ISRCTN05017507.