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Background: The 6-minute walking distance (6MWD) is an excellent measure of both functional endurance and health. The primary aim of this study was to estimate temporal trends in 6MWD for older Japanese adults between 1998 and 2017; the secondary aim was to estimate concurrent trends in body size (i.e., height and mass) and self-reported participation in exercise/sport., Methods: Adults aged 65-79 years were included. Annual nationally representative 6MWD data (n = 103,505) for the entire period were obtained from the Japanese Ministry of Education, Culture, Sports, Science and Technology. Temporal trends in means (and relative frequencies) were estimated at the gender-age level by best-fitting sample-weighted linear/polynomial regression models, with national trends estimated by a post-stratified population-weighting procedure. Temporal trends in distributional variability were estimated as the ratio of coefficients of variation., Results: Between 1998 and 2017 there was a steady, moderate improvement in mean 6MWD (absolute = 45 m (95% confidence interval (95%CI): 43-47); percent = 8.0% (95%CI: 7.6%-8.4%); effect size = 0.51 (95%CI: 0.48-0.54)). Gender- and age-related temporal differences in means were negligible. Variability in 6MWD declined substantially (ratio of coefficients of variation = 0.89, 95%CI: 0.87-0.92), with declines larger for women compared to men, and for 75-79-year-olds compared to 65-74-year-olds. Correspondingly, there were moderate and negligible increases in mean height and mass, respectively, and negligible increases in the percentage who participated in exercise/sport at least 3 days per week and at least 30 min per session., Conclusion: There has been a steady, moderate improvement in mean 6MWD for older Japanese adults since 1998, which is suggestive of corresponding improvements in both functional endurance and health. The substantial decline in variability indicates that the temporal improvement in mean 6MWD was not uniform across the distribution. Trends in 6MWD are probably influenced by corresponding trends in body size and/or participation in exercise/sport., (Copyright © 2021. Production and hosting by Elsevier B.V.)

Post-stroke fatigue (PSF) is a common symptom associated with disability and decreased quality of life. Distinction can be made between perceived fatigue and fatigability. The first aim of this study was to evaluate the prevalence of perceived fatigue and fatigability amongst patients with chronic stroke and to explore how these two parameters relate. The second aim was to study the relationship between modifiable factors (sleep disorders, anxiety, depression and activities of daily living) and fatigue in this population. Sixty-two patients with chronic stroke (> 6 months) were included. Perceived fatigue was evaluated using the Fatigue Severity Scale (FSS). Motor fatigability was assessed with the percent change in meters walked from first to last minute of the 6-min Walk Test and an isometric muscular fatigability test. Subjects also completed self-report questionnaires assessing anxiety and depression (Hospital Anxiety and Depression Scale-HADS), sleep quality (Pittsburgh Sleep Quality Index-PSQI) and activity limitations (ACTIVLIM-stroke). Seventy-one percent of participants presented PSF. There was no correlation between the FSS and motor fatigability. FSS significantly correlated with HADS-Anxiety (ρ = 0.53, P < 0.001), HADS-depression (ρ = 0.63, P < 0.001), PSQI (ρ = 0.51, P < 0.001) and ACTIVLIM (ρ = - 0.30, P < 0.05). A linear regression model showed that the HADS-Depression, the PSQI and the ACTIVLIM explained 46% of the variance of the FSS. A high proportion of chronic stroke patients presents PSF, with no relation between their fatigue and fatigability. Perceived fatigue is associated with potentially modifiable factors: anxious and depressive symptoms, poor sleep quality and activity limitations. Registered at ClinicalTrials.gov (NCT04277234) (21/02/2019).

Objective: To assess mexiletine's long-term safety and effect on 6-minute walk distance in a well-defined cohort of patients with myotonic dystrophy type 1 (DM1)., Methods: We performed a randomized, double-blind, placebo-controlled trial of mexiletine (150 mg 3 times daily) to evaluate its efficacy and safety in a homogenous cohort of adult ambulatory patients with DM1. The primary outcome was change in 6-minute walk distance at 6 months. Secondary outcomes included changes in hand grip myotonia, strength, swallowing, forced vital capacity, lean muscle mass, Myotonic Dystrophy Health Index scores, and 24-hour Holter and ECG results at 3 and 6 months., Results: Forty-two participants were randomized and 40 completed the 6-month follow-up (n = 20 in both groups). No significant effects of mexiletine were observed on 6-minute walk distance, but hand grip myotonia was improved with mexiletine treatment. There were no differences between the mexiletine and placebo groups with respect to the frequency or type of adverse events. Changes in PR, QRS, and QTc intervals were similar in mexiletine- and placebo-treated participants., Conclusions: There was no benefit of mexiletine on 6-minute walk distance at 6 months. Although mexiletine had a sustained positive effect on objectively measured hand grip myotonia, this was not seen in measures reflecting participants' perceptions of their myotonia. No effects of mexiletine on cardiac conduction measures were seen over the 6-month follow-up period., Classification of Evidence: This study provides Class I evidence that for ambulatory patients with DM1, mexiletine does not significantly change 6-minute walk distance at 6 months., (© 2020 American Academy of Neurology.)

An understanding of the dose-response during training is important to identify the rehabilitation programs to obtain the improvement in chronic stroke patients. The purpose of this study was to determine whether distance-dose (distance walked across all sessions) during robot-assisted training affects the change of walking speed and distance in chronic stroke patients after intervention. Fifteen chronic stroke patients were enrolled in this study. The patients performed 8 gait training sessions using the Hybrid Assistive Limb (HAL) for 3 weeks. Gait speed, stride length, cadence, and 2-minute walk test (2MWT) were measured before and post-intervention. Total walking distance (distance walked across all sessions) in individual patients were also measured. Gait speed, stride length, cadence, and 2-minute walk test (2MWT) improved significantly after training. The average of walking distance for 8 sessions in individual patients was 3793.3 ± 2105.3 m. Moreover, the change of gait speed (r = 0.53) and 2MWT (r = 0.70) were positively correlated with the walking distance during 8 sessions. This study of finding demonstrated that greater total distance walked over all sessions of training using the HAL is directly associated with the better walking outcomes in patients with chronic stroke. Further researches with a larger number of patients and a control group are needed to quantify the study results more precisely., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Health-related quality of life (HRQoL) should be seen as a tool that provides an overall view of the general clinical condition of a COPD patient. The aims of this study were to identify variables associated with HRQoL and whether they continue to have an influence in the medium term, during follow-up., Methods: Overall, 543 patients with COPD were included in this prospective observational longitudinal study. At all four visits during a 5-year follow-up, the patients completed the Saint George's Respiratory Questionnaire (SGRQ), pulmonary function tests, the 6-min walk test (6MWT), and a physical activity (PA) questionnaire, among others measurements. Data on hospitalization for COPD exacerbations and comorbidities were retrieved from the personal electronic clinical record of each patient at every visit., Results: The best fit to the data of the cohort was obtained with a beta-binomial distribution. The following variables were related over time to SGRQ components: age, inhaled medication, smoking habit, forced expiratory volume in one second, handgrip strength, 6MWT distance, body mass index, residual volume, diffusing capacity of the lung for carbon monoxide, PA (depending on level, 13 to 35% better HRQoL, in activity and impacts components), and hospitalizations (5 to 45% poorer HRQoL, depending on the component)., Conclusions: Among COPD patients, HRQoL was associated with the same variables throughout the study period (5-year follow-up), and the variables with the strongest influence were PA and hospitalizations.

Background: To evaluate the effectiveness and safety of technology-assisted rehabilitation following total hip/knee replacement (THR/TKR)., Methods: Six electronic databases were searched without language or time restrictions for relevant studies: MEDLINE, EMBASE, Cochrane Library, CINAHL, SPORTDiscus, Physiotherapy Evidence Database (PEDro); from inception to November 7th, 2018. Two reviewers independently applied inclusion criteria to select eligible randomised controlled trials (RCTs) that investigated the effectiveness of technology-based interventions, compared with usual care or no intervention for people undergoing THR/TKR. Two reviewers independently extracted trial details (e.g. patients' profile, intervention, outcomes, attrition and adverse events). Study methodological quality was assessed using the PEDro scale. Quality of evidence was critically appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach., Results: We identified 21 eligible studies assessing telerehabilitation, game- or web-based therapy. There were 17 studies (N = 2188) in post-TKR rehabilitation and 4 studies (N = 783) in post-THR rehabilitation. Compared to usual care, technology-based intervention was more effective in reducing pain (mean difference (MD): - 0.25; 95% confidence interval (CI): - 0.48, - 0.02; moderate evidence) and improving function measured with the timed up-and-go test (MD: -7.03; 95% CI: - 11.18, - 2.88) in people undergoing TKR. No between-group differences were observed in rates of hospital readmissions or treatment-related adverse events (AEs) in those studies., Conclusion: There is moderate-quality of evidence showed technology-assisted rehabilitation, in particular, telerehabilitation, results in a statistically significant improvement in pain; and low-quality of evidence for the improvement in functional mobility in people undergoing TKR. The effects were however too small to be clinically significant. For THR, there is very limited low-quality evidence shows no significant effects.

Objective: To compare the 6-minute walking distance (6MWD) in a population-based cohort of patients with osteoarthritis (OA) with that in matched peers from the general population, and to explore the associations between walking ability and risk of cardiovascular disease (CVD) in the OA cohort., Methods: This cross-sectional study included individuals (ages 40-80 years) who had self-reported OA (n = 500) in a previous population-based study and age- and sex-matched peers from the general population (n = 235). Clinical examinations of the patients with OA included classification according to the American College of Rheumatology criteria, blood sampling, and measuring arterial stiffness (PWV; pulse wave velocity). Group differences in the 6MWD were calculated with t-tests. The association between walking ability and CVD risk in the OA cohort was examined using multivariate regression models., Results: In the age-stratified analyses, the largest mean difference in the 6MWD was observed in the youngest age groups (40-49 years); female patients in the OA group walked 84.6 fewer meters compared with the reference group (579.4 meters and 663.9 meters, respectively; P < 0.001), and male patients walked 88.3 fewer meters compared with the reference group (619.9 meters and 708.3 meters, respectively; P = 0.001). In the OA group, the 6MWD was significantly associated with PWV in the adjusted analysis (P = 0.001); an increase in the walking distance of 100 meters corresponded to a reduction in PWV of 0.3 meters/second., Conclusion: Even at age 40 years, patients with OA had a significantly shorter mean walking distance compared with their matched peers, underlining the importance of an early clinical approach to OA. Furthermore, in the OA group, the 6MWD was significantly associated with arterial stiffness, suggesting that walking ability is important for the CVD risk profile in patients with OA., (© 2018, American College of Rheumatology.)

Background: Osteoarthritis (OA) is associated with worsening physical function and a high prevalence of comorbid health conditions. In particular, cardiovascular disease (CVD) risk is higher in individuals with OA than the general population. Limitations in physical function may be one pathway to the development of CVD among individuals with OA. This study evaluated associations of symptomatic knee OA (sxKOA), baseline physical function and worsening of function over time with self-reported incident CVD in a community-based cohort., Methods: Our sample consisted of individuals from the Johnston County Osteoarthritis Project who did not report having CVD at baseline. Variables used to evaluate physical function were the Health Assessment Questionnaire (HAQ), time to complete 5 chair stands, and the 8-ft walk. Worsening function for these variables was defined based on previous literature and cutoffs from our sample. Logistic regression analyses examined associations of sxKOA, baseline function and worsening of function over time with self-reported incident CVD, unadjusted and adjusted for relevant demographic and clinical characteristics., Results: Among 1709 participants included in these analyses, the mean age was 59.5 ± 9.5 years, 63.6% were women, 15% had sxKOA, and the follow up time was 5.9 ± 1.2 years. About a third of participants reported worsening HAQ score, about two-fifths had worsened chair stand time, half had worsened walking speed during the 8-ft walk, and 16% self-reported incident CVD. In unadjusted analyses, sxKOA, baseline function, and worsening function were all associated with self-reported incident CVD. In multivariable models including all of these variables, sxKOA was not associated with incident CVD, but worsening function was significantly associated with increased CVD risk, for all three functional measures: HAQ odds ratio (OR) = 2.49 (95% confidence interval (CI) 1.90-3.25), chair stands OR = 1.58 (95% CI 1.20-2.08), 8-ft walk OR = 1.53 (95%CI 1.15-2.04). These associations for worsening function remained in models additionally adjusted for demographic and clinical characteristics related to CVD risk., Conclusions: The association between symptomatic knee osteoarthritis and cardiovascular disease risk was explained by measures of physical function. This highlights the importance of physical activity and other strategies to prevent functional loss among individuals with symptomatic knee osteoarthritis.

Objectives: Exercise-based cardiac rehabilitation (CR) is an effective intervention for patients with heart failure (HF), in which one of the main targets is to increase physical capacity. In the HF population this is traditionally assessed using distance covered during a walking test. This study aims to establish the extent to which change in walking ability, in HF patients attending CR, is determined by patient characteristics and service provision., Methods: The study utilised routine clinical data from the National Audit of Cardiac Rehabilitation to perform a robust analysis. Change, in metres, between pre- and post-CR six-minute walk tests was calculated. Multivariate linear regression models were used to explore the relationship between patient characteristics, service-level variables, and change in metres walked., Results: Complete and valid data from 633 patients was analysed, and a mean change of 51.30 m was calculated. Female gender (-34.13 m, p = 0.007), being retired (-36.41 m, p = 0.001) and being married/in a relationship (-32.54 m, p = 0.023) were all significant negative predictors of change. There was an additional negative relationship with body mass index (BMI) whereby for every unit increase in BMI, predicted change reduces by 2.48 m (p = 0.006)., Conclusions: This study identified significant patient-level characteristics strongly associated with limited improvement in walking ability following CR. Improving physical capacity is a core component of CR, therefore services should aim to account for baseline characteristics identified in this study as part of tailoring the CR intervention around the individual. Pre- and post-CR physical capacity assessments, which constitute minimum standards for CR, are worryingly low and should be given high priority., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Using placebo data from 3 randomized multiple sclerosis (MS) trials with uniform inclusion criteria, we investigated heterogeneity of Expanded Disability Status Scale (EDSS) progression by geographical areas. Our analysis revealed a significantly lower EDSS progression in Eastern European countries (10.8%) compared with Western Europe (13.1%) or the USA/Canada (21.4%, p < 0.001); EDSS improvement behaved the same way. This heterogeneity is not explained by differences of baseline variables. No differences were detected on more easily quantifiable measures, the Timed 25-Foot Walk or the Multiple Sclerosis Functional Composite. At a time when disease progression represents the target for future interventions in MS, establishment of more quantitative and objective outcomes remains a key priority of MS research. Ann Neurol 2018;84:621-625., (© 2018 American Neurological Association.)

Objective: Cross-sectional studies have shown that spinal cord volume (SCV) loss is related to disease severity in multiple sclerosis (MS). However, long-term data are lacking. Our aim was to evaluate SCV loss as a biomarker of disease progression in comparison to other MRI measurements in a large cohort of patients with relapse-onset MS with 6-year follow-up., Methods: The upper cervical SCV, the total brain volume, and the brain T2 lesion volume were measured annually in 231 patients with MS (180 relapsing-remitting [RRMS] and 51 secondary progressive [SPMS]) over 6 years on 3-dimensional, T1-weighted, magnetization-prepared rapid-acquisition gradient echo images. Expanded Disability Status Scale (EDSS) score and relapses were recorded at every follow-up., Results: Patients with SPMS had lower baseline SCV ( p < 0.01) but no accelerated SCV loss compared to those with RRMS. Clinical relapses were found to predict SCV loss over time ( p < 0.05) in RRMS. Furthermore, SCV loss, but not total brain volume and T2 lesion volume, was a strong predictor of EDSS score worsening over time ( p < 0.05). The mean annual rate of SCV loss was the strongest MRI predictor for the mean annual EDSS score change of both RRMS and SPMS separately, while correlating stronger in SPMS. Every 1% increase of the annual SCV loss rate was associated with an extra 28% risk increase of disease progression in the following year in both groups., Conclusion: SCV loss over time relates to the number of clinical relapses in RRMS, but overall does not differ between RRMS and SPMS. SCV proved to be a strong predictor of physical disability and disease progression, indicating that SCV may be a suitable marker for monitoring disease activity and severity., (© 2018 American Academy of Neurology.)

Background: Impaired exercise capacity is the most disabling symptom in patients with heart failure with reduced ejection fraction (HFrEF). Despite sacubitril/valsartan showing reduced long-term morbidity and mortality over enalapril in HFrEF, its effects on short-term functional capacity remain uncertain. We sought to evaluate the effects of sacubitril/valsartan on a 30-day six-minute walk test in eligible patients with HFrEF., Methods and Results: From November 1, 2016 to February 1, 2017, a total of 58 stable symptomatic patients with HFrEF were eligible for sacubitril/valsartan and underwent 6-MWT before and 30days after initiation of sacubitril/valsartan therapy. A mixed-effects model for repeated-measures was used to analyze the changes. Mean age was 70±11years. 72.4% males, 46.6% with ischemic heart disease, and 51.7% on NYHA functional class III were included. The mean (SD) values of baseline LVEF and 6MWT were 30±7%, and 300±89m, respectively. The median (IQR) of NT-proBNP at baseline was 2701pg/ml (1087-4200). Compared with baseline, the 6-MWT distance increased significantly at 30days by 13.9% (+∆=41.8m (33.4-50.2); p<0.001)., Conclusions: In this pilot study, sacubitril/valsartan was associated with an improvement in exercise tolerance in symptomatic patients with HFrEF., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Objective: To determine if Functional Electrical Stimulation (FES) would improve ischemic pain, walking distance, and quality of life of patients with intermittent claudication., Design: Single blind, randomized block, two factorial design., Patients: Patients diagnosed with Peripheral Artery Disease (PAD) and intermittent claudication (IC). Ankle Brachial Index ranged 0.4-0.9 on at least one leg. Patients were randomly assigned to experimental (FES+Walk, N=13) or control (WALK, N=14) groups., Intervention: Experimental group patients received FES to the dorsiflexor and plantarflexor muscles while walking for 1h/day, six days/week for eight weeks. Control group patients received similar intervention without FES. A Follow-up period of both groups lasted eight weeks., Outcome Measures: Outcome measures were taken at baseline (T 0 ), after intervention (T 1 ), and after follow-up (T 2 ). Primary measures included Perceived Pain Intensity (PPI), Six minute walk (6MW), and Peripheral Arterial Disease Quality of Life (PADQOL). Secondary measures included Intermittent Claudication Questionnaire (ICQ) and Timed Up and Go (TUG)., Results: Group by time interactions in PPI were significant (P<0.001) with differences of 27.9 points at T 1 and 36.9 points at T 2 favoring the FES+Walk group. Groups difference in Symptoms and Limitations in Physical Function of the PADQOL reached significance (T 1 =8.9, and T 2 =8.3 improvements; P=0.007). ICQ was significant (T 1 =9.3 and T 2 =13.1 improvements; P=0.003). Improvement in 6MW and TUG tests were similar between groups., Conclusions and Relevance: Walking with FES markedly reduced ischemic pain and enhanced QOL compared to just walking. FES while walking may offer an effective treatment option for the elderly with PAD and Intermittent Claudication., Trial Registration: NIH-NIA 1R21AG048001 https://projectreporter.nih.gov/project&#95;info&#95;description.cfm?aid=8748641&icde=30695377&ddparam=&ddvalue=&ddsub=&cr=1&csb=default&cs=ASC. https://clinicaltrials.gov/ct2/show/NCT02384980?term=David+Embrey&rank=1., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)