Drop-out, adherence, and compliance in randomized controlled trials of exercise training in multiple sclerosis: Short report.

We documented reporting and rates of drop-out, adherence, and compliance from 40 randomized controlled trials (RCTs) included in our meta-analysis on safety of exercise training (ET) in MS. We adopted definitions and metrics of adherence and compliance provided by the MoXFo adherence group. Drop-out was reported in 100% of the RCTs and approximated 10% for intervention and control conditions. Adherence and compliance were reported in approximately 50% and 10% of the RCTs, respectively, and approximated 80% and 70%, respectively. Standardized metrics for reporting adherence and compliance are important in future RCTs for understanding the impact on outcomes and translation of research evidence into practice.

Free-living ambulatory physical activity and cognitive function in multiple sclerosis: the significance of step rate vs. step volume.

BACKGROUND: Physical activity (PA) represents a promising behavioral approach for managing cognitive dysfunction in multiple sclerosis (MS). However, there is a lack of information on the pattern of free-living PA intensity (e.g., step rate) and its unique association with cognition. Such information is essential for informing clinical trials in MS. OBJECTIVE: We examined associations among PA volume and intensity with cognitive function in persons with MS, and intensity was derived from steps-based metrics (peak 30-min cadence [Peak-30CAD], and time spent in incremental cadence bands). METHODS: We included data from 147 persons with MS who underwent assessments of cognitive function (via Brief International Cognitive Assessment in MS) and wore an ActiGraph GT3X + accelerometer for 7 days. We performed bivariate and partial correlations and regression analyses examining associations among PA metrics and cognitive outcomes. RESULTS: Higher Peak-30CAD was significantly associated with better performance in cognitive processing speed and verbal learning and memory (rs = 0.19-0.38), and the associations remained significant when controlling for daily steps, age, sex, and years of education (p < 0.05). By comparison, daily steps was only correlated with cognitive processing speed (rs = 0.26), and the association was non-significant when controlling for Peak-30CAD and covariates. There were stronger correlations among time spent in higher intensity cadence bands with cognitive performance (rs = 0.18-0.38). CONCLUSION: Our results highlight the important role of PA intensity for cognition in MS, and may inform future development of focal PA interventions that focusing on step rate patterns for improving cognition in persons with MS.

Updated Systematic Review and Quantitative Synthesis of Physical Activity Levels in Multiple Sclerosis.

OBJECTIVE: This article provided an updated quantitative synthesis of physical activity levels in persons with multiple sclerosis compared with controls and other clinical populations. DESIGN: A systematic search through PubMed, Scopus, and PsycINFO was conducted for articles published between August 2016 and July 2022. Articles that included a group comparison of at least one measurement of physical activity between adults with multiple sclerosis and controls or other clinical populations were included in the meta-analysis. RESULTS: Twenty-four studies met the inclusion criteria and yielded a total of 119 comparisons. There was a moderate difference in physical activity levels between persons with multiple sclerosis and controls (effect size = -0.56, P < 0.01), but no significant difference between persons with multiple sclerosis and other clinical populations (effect size = 0.01, P = 0.90). The pooled effect sizes comparing multiple sclerosis with controls ( Q104 = 457.9, P < 0.01) as well as with clinical populations ( Q13 = 108.4, P < 0.01) were heterogeneous. Moderating variables included sex, disability status, measurement method, outcome, intensity, and application of a multiple sclerosis-specific cut-point. CONCLUSIONS: Physical activity levels remain significantly lower in persons with multiple sclerosis compared with controls, but the magnitude of difference has become smaller over the past decade. There is a need for continued development of effective physical activity programs that can reach the greater community with multiple sclerosis.

Systematic review and meta-analysis of sedentary behavior in persons with multiple sclerosis.

BACKGROUND: Persons with multiple sclerosis (MS) engage in less physical activity than the general population, and the disease manifestations and comorbidity conditions might further predispose them toward sedentary behavior (SB) among this population. We performed a systematic review with meta-analysis of studies that compared SB in persons with MS and non-MS controls, and examined factors that may moderate the difference in SB between the two groups. METHODS: We conducted a systematic search using PubMed, PsycINFO, Scopus, and CINAHL from inception up to August 2022, and identified studies that involved group comparison of SB outcomes between MS and non-MS controls. Effect sizes were calculated as standardized mean differences (SMDs) using Hedge's g. We generated a multilevel random-effects model for estimating an overall effect, and performed moderator analyses. Methodological quality was assessed using the Appraisal Tool for Cross-Sectional Studies (AXIS tool). RESULTS: Eleven studies were included (1403 MS vs. 449 controls) and yielded 17 effects for meta-analysis. Results indicated an overall small, but significant effect (SMD [95% CI] = 0.27 [0.02, 0.53], p = 0.03) with significant heterogeneity (Q16 = 72.2, p < 0.01; I2total = 75.8%). There were larger effects when the MS sample had a higher proportion of females, or when SB was reported as percent sedentary time per day compared with other SB outcomes (p = 0.03 and 0.05, respectively). The included studies achieved fairly good quality (91.4%) using the AXIS tool. CONCLUSIONS: The cumulative evidence supports that persons with MS engage in more SB than non-MS controls. Our findings may support the design of targeted behavioral change interventions for reducing SB and improving health and function in the MS population.

Free-Living Peak Cadence in Multiple Sclerosis: A New Measure of Real-World Walking?

BACKGROUND: Physical function and walking performance have become important outcomes in clinical trials and rehabilitation involving persons with multiple sclerosis (MS). However, assessments conducted in controlled settings may not reflect real-world capacity and movement in a natural environment. Peak cadence via accelerometry might represent a novel measure of walking intensity and prolonged natural effort under free-living conditions. OBJECTIVE: We compared peak 30-minute cadence, peak 1-minute cadence, and time spent in incremental cadence bands between persons with MS and healthy controls, and examined the associations between peak cadence and laboratory-assessed physical function and walking performance. METHODS: Participants (147 MS and 54 healthy controls) completed questionnaires on disability status and self-reported physical activity, underwent the Short Physical Performance Battery, Timed 25-Foot Walk, Timed Up and Go, and 6-Minute Walk, and wore an accelerometer for 7 days. We performed independent samples t-tests and Spearman bivariate and partial correlations adjusting for daily steps. RESULTS: The MS sample demonstrated lower physical function and walking performance scores, daily steps, and peak cadence (P < .001), and spent less time in purposeful steps and slow-to-brisk walking (40-119 steps/minutes), but accumulated more incidental movement (1-19 steps/minutes) than healthy controls. The associations between peak cadence and performance outcomes were strong in MS (|rs| = 0.59-0.68) and remained significant after controlling for daily steps (|prs| = 0.22-0.44), P-values < .01. Peak cadence was inversely correlated with age and disability, regardless of daily steps (P < .01). CONCLUSIONS: Our findings provide preliminary evidence for the potential use of peak cadence with step-based metrics for comprehensively evaluating free-living walking performance in MS.

CD300ld on neutrophils is required for tumour-driven immune suppression.

The immune-suppressive tumour microenvironment represents a major obstacle to effective immunotherapy1,2. Pathologically activated neutrophils, also known as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), are a critical component of the tumour microenvironment and have crucial roles in tumour progression and therapy resistance2-4. Identification of the key molecules on PMN-MDSCs is required to selectively target these cells for tumour treatment. Here, we performed an in vivo CRISPR-Cas9 screen in a tumour mouse model and identified CD300ld as a top candidate of tumour-favouring receptors. CD300ld is specifically expressed in normal neutrophils and is upregulated in PMN-MDSCs upon tumour-bearing. CD300ld knockout inhibits the development of multiple tumour types in a PMN-MDSC-dependent manner. CD300ld is required for the recruitment of PMN-MDSCs into tumours and their function to suppress T cell activation. CD300ld acts via the STAT3-S100A8/A9 axis, and knockout of Cd300ld reverses the tumour immune-suppressive microenvironment. CD300ld is upregulated in human cancers and shows an unfavourable correlation with patient survival. Blocking CD300ld activity inhibits tumour development and has synergistic effects with anti-PD1. Our study identifies CD300ld as a critical immune suppressor present on PMN-MDSCs, being required for tumour immune resistance and providing a potential target for cancer immunotherapy.

Effects of aerobic, resistance, and combined exercise training on health-related quality of life in multiple sclerosis: Systematic review and meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated, neurodegenerative disease of the central nervous system that manifests in symptoms that compromise health-related quality of life (HRQOL). HRQOL focuses on a person's overall, subjective evaluation of health status primarily in the physical and mental domains. Exercise training is a form of rehabilitation for managing MS-related outcomes that might influence HRQOL. Reviews on exercise training are available, but we are unaware of a recent comprehensive review and meta-analysis of exercise effects for improving physical and mental domains of HRQOL. This analysis provides an updated review and meta-analysis of randomized controlled trials (RCTs) examining interventions consisting of aerobic, resistance and combined exercise training for improving HRQOL in persons with MS. This systematic review 1) assessed the overall strength of evidence for exercise interventions on HRQOL, 2) evaluated the relative effect of exercise interventions on physical and mental domains of HRQOL, and 3) determined moderators of exercise intervention effects on HRQOL. METHODS: Seven databases were searched for RCTs evaluating physical and/or mental domains of HRQOL with adults diagnosed with MS and undergoing an intervention of aerobic, resistance or combined exercise training compared with a non-exercise comparator. Data extraction included participant and intervention characteristics, and pre- and post-intervention HRQOL outcome data. Effect sizes (ESs) were calculated as standardized mean differences (SMDs) and a multilevel random-effects model was used to generate an aggregated SMD that compared exercise with non-exercise control conditions. RESULTS: Twelve RCTs met the inclusion criteria and yielded 23 ESs to be analyzed. Participants (N = 593; 308 intervention vs. 285 control conditions) had a mean (±standard deviation) age of 42.4 (6.5) years and 80% (18.3%) were female. Results generated a medium effect of exercise for improving overall HRQOL (ES=0.64, p = 0.0001) with high heterogeneity (Q11=58.8, I2=86.7%). Exercise training yielded a large effect on the physical domain (k = 12, ES=0.82, p<0.0009) and a medium effect on the mental domain (k = 11, ES=0.41, p<0.0001). Moderator analyses identified exercise modality, supervision level, intervention delivery and length, HRQOL tool, and number of participants with relapsing-remitting MS as significant influences of ES for HRQOL. CONCLUSIONS: Exercise training is clinically effective for improving overall HRQOL in MS and produces greater improvements in the physical domain of HRQOL than the mental domain. The moderator analysis suggests that supervised, aerobic, and group-delivered exercise training of ≥3 months yields the most influence on HRQOL. Such results may have major implications for MS treatment and care.

Vascular function and cognition in persons with multiple sclerosis: Preliminary examination.

BACKGROUND: Cognitive dysfunction is one of the most common consequences of multiple sclerosis (MS). Recent studies have noted a high incidence of vascular comorbidity that might be associated with cognitive decline among persons with MS. However, there is a lack of evidence on vascular biomarkers (e.g., arterial stiffness indices) that are associated with cognition in MS. The current study characterized differences in vascular function between persons with MS and healthy controls, and examined the association between vascular and cognitive function in persons with MS compared with healthy controls. RESULTS: The MS group had significantly worse cognitive performance and higher cfPWV than healthy controls. There were significant bivariate correlations between the Symbol Digit Modalities Test (SDMT) score with AIx75 (rs = -0.45) and cfPWV (rs = 0.30) in the MS sample, but not in healthy controls. Regression analyses further indicated a nonlinear association between cfPWV and the SDMT in the MS sample (p-values for ß coefficients < 0.05; adjusted R2 = 0.10). No significant associations were observed among other cognitive and vascular outcomes. CONCLUSION: Our findings suggest significant associations between arterial stiffness and cognitive processing speed in MS. This preliminary examination provides initial, cross-sectional support for future population-based research on cognitive and vascular function in persons with MS. Such results may be clinically important for developing interventions that focus on regulating vascular dysfunction as an early treatment for preventing cognitive impairment in the MS population.

Validity of the 30-Second Sit-to-Stand test as a measure of lower extremity function in persons with multiple sclerosis: Preliminary evidence.

BACKGROUND: The 30-Second Sit-To-Stand (30SSTS) is a quick, inexpensive, safe, and widely used clinical measure of lower extremity function. To date, there is limited evidence regarding the use of 30SSTS in multiple sclerosis (MS). The purpose of this study was to examine the construct validity of the 30SSTS test in persons with MS compared with non-MS healthy controls. METHODS: Twenty ambulatory persons with MS and twenty age- and sex-matched healthy controls completed the 30SSTS, Timed 25-Foot Walk (T25FW), Timed Up and Go (TUG), Six-Minute Walk (6MW), and Godin Leisure-Time Exercise Questionnaire (GLTEQ). Persons with MS also completed the Patient Determined Disease Steps (PDDS) and 12-item MS Walking Scale (MSWS-12). RESULTS: Persons with MS had significantly worse performance on the TUG (mean difference [95% confidence interval] = 1.4 [0.5, 2.3] sec) and 6MW (-259.2 [-450.8, -67.6] ft), but not on the 30SSTS (-1.6 [-1.5, 4.6] reps) and T25FW (-0.59 [-0.1, 1.2] ft/sec) compared with controls. There were significant moderate-to-strong correlations between the 30SSTS with T25FW, TUG, and 6MW scores in persons with MS (r = 0.48, -0.65 and 0.61, respectively), whereas the 30SSTS was only significantly associated with 6MW scores (r = 0.43) in controls. The 30SSTS was negatively associated with MS-related walking disability assessed by the PDDS and MSWS-12 (rs = -0.52 and -0.64, respectively), but was not significantly associated with the GLTEQ in MS and controls (r = 0.30 and 0.17, respectively). CONCLUSION: This study provides initial support for the construct validity of the 30SSTS as a measure of lower extremity function in persons with MS. Our findings warrant the inclusion of the 30SSTS as a feasible and valid measure of physical function in clinical research and practice involving persons with MS.

Dose-Response Association Between Physical Activity (Daily MIMS, Peak 30-Minute MIMS) and Cognitive Function Among Older Adults: NHANES 2011-2014.

BACKGROUND: The purpose of this study was to determine the dose-response association between habitual physical activity (PA) and cognitive function using a nationally representative data set of U.S. older adults aged ≥60 years. METHODS: We used data from the 2011-2014 National Health and Nutrition Examination Survey (n = 2 441, mean [SE] age: 69.1 [0.2] years, 54.7% females). Cognitive function was assessed using the digit symbol substitution test (DSST) and animal fluency test (AFT). Habitual PA was collected using a triaxial accelerometer worn on participants' nondominant wrist. PA was expressed as 2 metrics using monitor-independent movement summary (MIMS) units: the average of Daily MIMS (MIMS/day) and peak 30-minute MIMS (Peak-30MIMS; the average of the highest 30 MIMS min/d). Sample weight-adjusted multivariable linear regression was performed to determine the relationship between each cognitive score and MIMS metric while adjusting for covariates. RESULTS: After controlling for covariates, for each 1 000-unit increase in Daily MIMS, DSST score increased (ß-coefficient [95% CIs]) by 0.67 (0.40, 0.93), whereas AFT score increased by 0.13 (0.04, 0.22); for each 1-unit increase in Peak-30MIMS, DSST score increased by 0.56 (0.42, 0.70), whereas AFT score increased by 0.10 (0.05, 0.15), all p < .001. When including both MIMS metrics in a single model, the association between Peak-30MIMS and cognitive scores remained significant (p < .01), whereas Daily MIMS did not. CONCLUSIONS: Our findings suggest that higher PA (both daily accumulated and peak effort) is associated with better cognitive function in the U.S. older adult population.

Cadence-based classification of moderate-intensity overground walking in 41- to 85-year-old adults.

BACKGROUND: Walking cadence (steps/min) has emerged as a valid proxy of physical activity intensity, with consensus across numerous laboratory-based treadmill studies that ≥100 steps/min approximates absolutely defined moderate intensity (≥3 metabolic equivalents; METs). We recently reported that this cadence threshold had a classification accuracy of 73.3% for identifying moderate intensity during preferred pace overground walking in young adults. The purpose of this study was to evaluate and compare the performance of a cadence threshold of ≥100 steps/min for correctly classifying moderate intensity during overground walking in middle- and older-aged adults. METHODS: Participants (N = 174, 48.3% female, 41-85 years of age) completed laboratory-based cross-sectional study involving an indoor 5-min overground walking trial at their preferred pace. Steps were manually counted and converted to cadence (total steps/5 min). Intensity was measured using indirect calorimetry and expressed as METs. Classification accuracy (sensitivity, specificity, accuracy) of a cadence threshold of ≥100 steps/min to identify individuals walking at ≥3 METs was calculated. RESULTS: The ≥100 steps/min threshold demonstrated accuracy of 74.7% for classifying moderate intensity. When comparing middle- vs. older-aged adults, similar accuracy (73.4% vs. 75.8%, respectively) and specificity (33.3% vs. 34.5%) were observed. Sensitivity was high, but was lower for middle- vs. older-aged adults (85.2% vs. 93.9%, respectively). CONCLUSION: A cadence threshold of ≥100 steps/min accurately identified moderate-intensity overground walking. Furthermore, accuracy was similar when comparing middle- and older-aged adults. These findings extend our previous analysis in younger adults and confirm the appropriateness of applying this cadence threshold across the adult lifespan.

Health and Fitness Comparisons Among Middle-Aged and Older Adults with Long-Term Participation in Four Different Sports.

Physical activity is known to confer numerous health benefits. However, few studies have assessed the prolonged impact of participation in different sports on health and fitness. The purpose of this cross-sectional study was to compare the impact of long-term participation (i.e., ≥9 years) in four different sports, including two traditional Chinese (Tai Chi; diabolo) and two modern sports (aerobics; track and field [TF]) on health and fitness measures among middle-aged and older adults. Participants (n=252, 56.6±8.5y, 66% female) completed the following measures: height, weight, BMI, waist circumference, waist-hip ratio (WHR), body fat%, resting blood pressure (BP) and heart rate, vital capacity, grip strength, reaction time, flexibility, balance. Compared to Tai Chi, aerobics was associated with lower systolic BP and fat%, and greater vital capacity, while TF was associated with lower systolic BP, shorter reaction time, greater vital capacity and better balance (p-values<0.05). Diabolo was associated with lower WHR compared to aerobics and Tai Chi, and greater vital capacity than Tai Chi (p-values<0.05). No significant differences were observed across sports in other measures. Long-term participation in four sports might have different effects on BP, vital capacity, balance, reaction time, body fat, and central adiposity. Individuals who prefer to choose traditional sports (Tai Chi, diabolo) may anticipate similar long-term effects on resting heart rate, BMI, muscle mass, and grip strength compared to those who perform modern sports (aerobics, TF). Information presented in this study may be valuable when designing population, group and individually-tailored PA recommendations in culturally diverse individuals.

Microblog data analysis of emotional reactions to COVID-19 in China.

To explore the emotional attitudes of microblog users in the different COVID-19 stages in China, this study used data mining and machine-learning methods to crawl 112,537 Sina COVID-19- related microblogs and conduct sentiment and group difference analyses. It was found that: (1) the microblog users' emotions shifted from negative to positive from the second COVID-19 pandemic phase; (2) there were no significant differences in the microblog users' emotions in the different regions; (3) males were more optimistic than females in the early stages of the pandemic; however, females were more optimistic than males in the last three stages; and (4) females posted more microblogs and expressed more sadness and fear while males expressed more anger and disgust. This research captured online information in real-time, with the results providing a reference for future research into public opinion and emotional reactions to crises.

Classification of moderate-intensity overground walking speed in 21- to 85-year-old adults.

The Compendium of Physical Activities reports that walking at 2.5 mph associates with absolutely-defined moderate intensity (i.e., ≥3 metabolic equivalents [METs]). However, it is unclear whether this speed threshold is accurate during overground walking and/or across the adult age-span. This study aimed to identify optimal and heuristic speed thresholds associated with 3 METs during overground walking across age groups. Healthy adults (n = 248, 21-85 years old, 49% women) performed a 5-minute self-paced overground walking trial. Speed was measured using an electronic gait mat, and oxygen uptake was measured using indirect calorimetry and converted to METs. Optimal and heuristic thresholds and classification accuracy metrics were determined and compared using ROC curve analyses. Speed thresholds (95% CIs) associated with 3 METs for the whole sample, young (21-40 years), middle-aged (41-60 years) and older-aged (61-85 years) groups were 1.29 (1.25, 1.33), 1.30 (1,26, 1,35), and 1.25 (1.21, 1.29) m/s, respectively. Overall, 3 mph and 5 km/h performed better than 2.5 mph and 4.5 km/h in balancing both sensitivity and specificity (higher Youden's Indices). Overground walking speeds associated with 3 METs were similar across age groups. A heuristic threshold of 3 mph or 5 km/h may better identify absolutely-defined moderate intensity overground walking.

Mass quarantine and mental health during COVID-19: A meta-analysis.

To reveal the complex relationships between quarantine and mental health during COVID-19, a meta-analysis was conducted involving 34 articles and a total sample size of 134,061. As the relationship between quarantine and mental health was found to be affected by the sampling objects and national factors, a random-effects model was applied for the meta-analysis. First, a heterogeneity test and sensitivity analysis were conducted to determine whether there was heterogeneity in the samples, after which a funnel chart, Rosenthal's Classic Fail-safe N test and Egger's test were applied to further determine whether there was publication bias in the included samples. Finally, a sub-group test was used to explore whether the sampling group and the country of origin had a moderating effect on the relationship between quarantine and mental health, which revealed that the relationship between quarantine and mental health was regulated and influenced by the sampled objects but was not affected by the country categories. The results indicated that: COVID-19 quarantine had varying impacts on individual anxiety, depression, and psychological stress; different groups had different regulatory effects on the relationship between quarantine and mental health; and country of origin had no moderating effect on quarantine and psychology. BACKGROUND: COVID-19 is the most important topic in 2020, and mass quarantine is the measures for pandemic prevention and control around the world since 2020. To explore the relationships between mass quarantine and mental health during COVID-19, a meta-analysis was conducted involving 28 articles and a total sample size of 134,061. METHOD: As the relationship between mass quarantine and mental health was found to be affected by the sampling objects and national factors, a random-effects model was applied for the meta-analysis. First, a heterogeneity test and sensitivity analysis were conducted to determine whether there was heterogeneity in the samples, after which a funnel chart, Rosenthal's Classic Fail-safe N test and Egger's test were applied to further determine whether there was publication bias in the included samples. Finally, a sub-group test was used to explore whether the sampling group and the country of origin had a moderating effect on the relationship between mass quarantine and mental health. RESULTS: COVID-19 quarantine had varying impacts on individual anxiety, depression, and psychological stress; different groups had different regulatory effects on the relationship between quarantine and mental health; and country of origin had no moderating effect on quarantine and mental health. CONCLUSIONS: This study employed a meta-analysis to examine the relationships between the COVID-19 pandemic mass quarantine measures and mental health factors such as anxiety, depression and stress, from which it was found that influence of quarantine on anxiety was stronger, the relationship between quarantine and mental health was affected by the sampled object, and there was no significant relationship between quarantine and country of origin in the sample population.