Oxygen Cost of Walking in People With Multiple Sclerosis and Its Association With Fatigue: A Systematic Review and Meta-analysis.

Background: This systematic review and meta-analysis aimed to compare the oxygen cost of walking in individuals with multiple sclerosis (MS) and controls and to assess the relationship between oxygen cost of walking and fatigue in individuals with MS. Methods: Four databases (CINAHL, MEDLINE, ProQuest, Web of Science) were searched up to September 2020. Studies were included if they recruited adults with MS and either compared oxygen cost of walking in those with MS and a control population or determined the relationship between oxygen cost of walking and fatigue. Meta-analysis of the standardized mean difference in oxygen cost of walking between individuals with MS and controls was performed. Results: Nine studies were included in this review, of which 7 compared oxygen cost of walking in individuals with MS (n = 176) and controls (n = 142) and 4 investigated the relationship between oxygen cost of walking and fatigue. Meta-analysis revealed that individuals with MS (with predominantly mild-to-moderate disability) had a significantly higher oxygen cost of walking compared with controls (standardized mean difference = 2.21, 95% CI = 0.88 to 3.54, P = .001). In addition, 3 studies found a significant yet weak positive association between oxygen cost of walking and fatigue. Conclusions: Individuals with MS expend more energy when walking compared with controls. This increase in energy expenditure may contribute to the development of fatigue, as some studies found that higher oxygen costs of walking were associated with greater fatigue. Future studies should investigate whether reducing energy expenditure during movement improves fatigue.

Establishing a Dose-Response Relationship Between Opioid Use and Hypogonadism: A Retrospective Case-Control Study.

Background: Opioid-induced androgen deficiency (OPIAD) related to chronic, long-acting opioid use can be a significant detriment to patient quality of life. The aim of this study was to investigate the association between chronic opioid use and hypogonadism. Methods: A single-center, retrospective, matched case-control analysis of 357 males (94 cases, 263 controls, aiming for 1:4 matching) was performed. Study subjects were ages 18 to 80 years and had a diagnosis of chronic opioid use. Patients with a hypogonadism diagnosis were matched to patients without a hypogonadism diagnosis by age, ethnicity, and body mass index. The maximum morphine equivalent daily dose (MEDD) was compared in each group. Results: A significant linear association between MEDD and the odds of developing hypogonadism (P<0.001) in males with chronic use of opioids was observed, with an odds ratio of 1.44 (95% CI 1.16-1.78) by 100-unit difference in maximum MEDD. Conclusion: Results showed a significant, positive linear association between chronic opioid dose and the odds of developing hypogonadism in males. This higher index of suspicion of OPIAD could lead to earlier recognition of symptoms and increase the positive predictive value of diagnostic laboratory tests.

Physical activity is associated with neuromuscular and physical function in patients with multiple sclerosis independent of disease severity.

PURPOSE: Examine the association between physical activity and neuromuscular and physical function in patients with multiple sclerosis when also considering disease severity. METHODS: 91 patients with multiple sclerosis were enrolled. Assessments included physical activity by 7-day thigh-worn accelerometry, knee extensor neuromuscular function by dynamometry (maximal isometric muscle strength, rate of force development (0-50 ms)), and physical function by 5× sit-to-stand, 2-min walk test, and timed 25 ft walk test. Physical activity tertile comparisons along with simple and multiple regressions (adjusting for age, gender, EDSS, time since diagnosis) were performed. RESULTS: Physical activity tertiles revealed differences (p < 0.05) in maximal muscle strength (1.77 ≈ 1.97 < 2.28 Nm/kg), rate of force development (4.66 < 8.03 ≈ 10.55 Nm/kg/s), 5× sit-to-stand (11.4 ≈ 9.7 > 8.5 s), 2-min walk test (153 < 183 < 207 m), and timed 25 ft walk test (6.3 > 4.4 > 4.3 s). Moreover, physical activity was associated (p < 0.05) with maximal muscle strength and rate of force development (r2 = 0.13-0.15) along with 5× sit-to-stand, 2-min walk test, and timed 25 ft walk test (r2 = 0.18-0.24), also after adjusting for age + gender + EDSS + time since diagnosis (r2 = 0.25-0.37 and 0.24-0.52), with physical activity consistently being a strong predictor. CONCLUSIONS: Higher levels of physical activity are associated with greater neuromuscular and physical function in ambulatory patients with multiple sclerosis independent of disease severity. These findings emphasize the importance of performing regular physical activity at all stages of multiple sclerosis.IMPLICATIONS FOR REHABILITATIONPhysical activity is associated with neuromuscular and physical function, independent of disease severity.Physical activity may be important in improving or preserving neuromuscular and physical function at all stages of ambulatory multiple sclerosis patients, yet longitudinal studies are warranted.Clinicians and rehabilitation professionals should encourage ambulatory patients at all stages of their disease to be as physically active as possible.

Upper limb rehabilitation interventions using virtual reality for people with multiple sclerosis: A systematic review.

BACKGROUND: Research on Virtual Reality (VR) based motor rehabilitation for people with multiple sclerosis (MS) is rapidly growing in popularity, although few studies have focused on the upper limb (UL). The aims of this review were to investigate the effect of VR interventions on UL function in people with MS and determine if the type of VR intervention influences intervention effect. METHOD: Five databases (IEEE Xplore, MEDLINE, ProQuest Central (Health & Medical Collection), Science Direct and Web of Science Core Collection) were searched using keywords that relating to MS, VR and UL. RESULTS: Ten articles were included, six randomised controlled trials, three cohort studies and one pilot observational study. Both commercial and custom VR technologies were used in interventions, along with combination approaches using robotics, electrical stimulation and occupational therapy. Using the Nine Hole Peg Test, two studies found significant improvements within groups, one found that VR was more effective than another gaming approach. Significant improvements in other UL measures were in the Fugl-Meyer Assessment for the proximal arm; handgrip; perceived strength; Jebsen-Taylor Hand Function Test; Wolf Motor Function Test; active range of motion and trajectory measures after VR intervention. There were conflicting results regarding if VR was more effective than conventional approaches. CONCLUSION: There is therefore some evidence that VR is effective in improving motor function in the UL, however, there is no clear consensus on which VR based approaches are the most effective, or the optimum intervention duration and intensity. Moreover, as many of the studies had non-immersive approaches it is hard to determine how effective immersion based approaches maybe in such specific context.

Systematic Review of Changes and Recovery in Physical Function and Fitness After Severe Acute Respiratory Syndrome-Related Coronavirus Infection: Implications for COVID-19 Rehabilitation.

OBJECTIVE: This review sought to (1) compare physical function and fitness outcomes in people infected with Severe Acute Respiratory Syndrome-related Coronavirus (SARS-CoV) with healthy controls, (2) quantify the recovery of physical function and fitness following SARS-CoV infection, and (3) determine the effects of exercise following SARS-CoV infection. METHODS: Four databases (CINAHL, MEDLINE, ProQuest, and Web of Science Core Collections) were searched in April 2020 using keywords relating to SARS-CoV, physical function, fitness, and exercise. Observational studies or randomized controlled trials were included if they involved people following SARS-CoV infection and either assessed the change or recovery in physical function/fitness or evaluated the effects exercise postinfection. RESULTS: A total 10 articles were included in this review. Evidence from 9 articles demonstrated that SARS-CoV patients had reduced levels of physical function and fitness postinfection compared with healthy controls. Furthermore, patients demonstrated incomplete recovery of physical function, with some experiencing residual impairments 1 to 2 years postinfection. Evidence from 1 randomized controlled trial found that a combined aerobic and resistance training intervention significantly improved physical function and fitness postinfection compared with a control group. CONCLUSIONS: Physical function and fitness are impaired following SARS-CoV infection, and impairments may persist up to 1 to 2 years postinfection. Researchers and clinicians can use these findings to understand the potential impairments and rehabilitation needs of people recovering from the current coronavirus 2019 (COVID-19) outbreak. While 1 study demonstrated that exercise can improve physical function and fitness postinfection, further research is required to determine the effectiveness of exercise in people recovering from similar infections (eg, COVID-19). IMPACT: Considering the similarities in pathology and clinical presentation of SARS-CoV and COVID-19, it is likely that COVID-19 patients will present with similar impairments to physical function. Accordingly, research is required to measure the extent of functional impairments in COVID-19 cohorts. In addition, research should evaluate whether rehabilitation interventions such as exercise can promote postinfection recovery.

Correlates of dual-task performance in people with multiple sclerosis: A systematic review.

BACKGROUND: Gait, balance, and cognitive disorders are common in people with Multiple Sclerosis (MS). In addition, people with MS have impaired ability to concurrently perform gait/balance and cognitive tasks due to cognitive-motor interference (CMI). Clinical features of MS may affect CMI; however, the relationship between CMI and clinical features of MS remains unclear. RESEARCH QUESTION: Are clinical features of MS associated with CMI? METHODS: A systematic review was conducted, and four databases (CINAHL, MEDLINE, ProQuest, and Web of Science Core Collections) were searched up to March 2019 using a combination of keywords related to MS and dual-tasking/CMI. Cross-sectional or longitudinal studies that reported the association between CMI and clinical features of MS were included in the review. The correlation coefficient for the relationship between CMI and clinical features of MS were extracted and the results were categorized according to the clinical feature measured. RESULTS: 13 studies were included in this review, of which nine investigated the association between CMI and disability and cognition, and four investigated the association between CMI and other clinical features of MS. While some studies reported that disability and cognition were negatively associated with CMI, the evidence was inconsistent regarding the magnitude and presence of these relationships. In addition, the relationship between CMI and other clinical features of MS (balance, falls risk, fatigue, anxiety, depression, pain, spasticity) remains unclear. SIGNIFICANCE: This review presents evidence from a small number of studies that suggests disability and cognition are negatively associated with CMI in people with MS, indicating that greater disability and cognitive dysfunction may be associated with lower dual-task performance. These findings highlight the potential importance of disability and cognition in the measurement and rehabilitation of people with dual-task impairments. However, further research is required to confirm these findings and determine the relationship between CMI and other clinical features of MS included in this review.

Exercise in the management of multiple sclerosis relapses: current evidence and future perspectives.

Relapses are a common feature of multiple sclerosis; however, recovery from relapses is often incomplete, with up to half of people experiencing residual disabilities postrelapse. Therefore, treatments are required to promote recovery of function and reduce the extent of residual disabilities postrelapse. Accordingly, this Perspective article explores the role of exercise in relapse management. Current evidence from two studies suggests that exercise in combination with steroid therapy improves disability and quality of life postrelapse, and may be more beneficial in promoting relapse recovery than steroid therapy alone. However, given the small number of studies and methodological limitations, further studies are required to understand the effects of exercise in relapse management and the mechanism through which exercise influences relapse recovery.

Minimally important difference of the fatigue severity scale and modified fatigue impact scale in people with multiple sclerosis.

BACKGROUND: Fatigue is a common and debilitating symptom of Multiple Sclerosis (MS); however, it is unknown what constitutes a clinically significant change in fatigue. Establishing the minimally important difference (MID) of fatigue outcome measures can inform the interpretation of changes in fatigue by estimating the level of change that is considered clinically relevant. AIM: Determine the MID for the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) in people with MS. METHODS: This cross-sectional study collected information on self-reported fatigue (FSS and MFIS) and quality of life (EQ-5D and MS Impact Scale 29) through an online survey. Anchor-based methods were used to estimate MID, and ordinal logistic regression models were used to determine the difference in fatigue that would predict a significant effect on quality of life. RESULTS: 365 people with MS (81.9% female, 69.3% relapsing-remitting MS, mean age 46.2 ±â€¯11.6 years, mean time since diagnosis 9.6 ±â€¯8.7 years) responded to the survey. MID estimates for the FSS and MFIS ranged from 0.45-0.88 and 3.86-8.11 respectively, accounting for 6.4-12.6% of maximum FSS score and 4.6-9.7% of maximum MFIS score. CONCLUSIONS: MID estimates derived from this study indicate that a difference of at least 0.45 points on the FSS or 4 points on the MFIS constitutes a clinically significant difference in fatigue. Therefore, these estimates represent a threshold value which can be used to interpret changes in the FSS and MFIS over time or in response to an intervention.

Is Fatigue Associated With Aerobic Capacity and Muscle Strength in People With Multiple Sclerosis: A Systematic Review and Meta-analysis.

OBJECTIVE: To determine the relationship between self-reported fatigue and aerobic capacity and muscle strength in people with multiple sclerosis (MS). DATA SOURCES: Four databases (Cumulative Index to Nursing and Allied Health, MEDLINE, ProQuest, and Web of Science Core Collections) were searched up to October 2018. STUDY SELECTION: Cross-sectional or longitudinal studies that reported the association between self-reported fatigue and aerobic capacity or objectively measured muscle strength in people with MS were included. DATA EXTRACTION: Study details, participant demographics, outcome measurement protocols, and the correlation coefficient derived from the association between fatigue and aerobic capacity or muscle strength at baseline was extracted, and methodological quality of included studies was assessed using the Joanna Briggs Institute Appraisal Checklist for Analytical Cross-sectional Studies. DATA SYNTHESIS: Ten studies were identified, of which 5 examined the association between fatigue and aerobic capacity and 7 examined the association between fatigue and muscle strength. Meta-analysis of the extracted correlation coefficients was performed using the Hedges-Olkin method, and pooled correlation coefficients demonstrated a moderate negative association between fatigue and aerobic capacity (r=-0.471; 95% CI, -0.644 to -0.251; P<.001) and a weak negative association between fatigue and muscle strength (r=-0.224; 95% CI, -0.399 to -0.032; P=.022). CONCLUSIONS: The results of this meta-analysis suggest that higher levels of aerobic capacity are associated with lower fatigue. Therefore, this finding highlights the potential role of aerobic exercise interventions in managing fatigue. Conversely, the relationship between fatigue and muscle strength was weak and inconsistent, and further studies are required to examine the association between these variables.

Effectiveness of Fatigue Management Interventions in Reducing Severity and Impact of Fatigue in People with Progressive Multiple Sclerosis: A Systematic Review.

BACKGROUND: Rehabilitation interventions are recommended to manage multiple sclerosis (MS)-related fatigue. However, existing research has largely been generalized to those with relapsing-remitting MS, making it difficult to determine the effectiveness of these interventions in people with progressive MS. Therefore, this study aimed to systematically review the evidence related to the effectiveness of fatigue management interventions in reducing the severity and impact of fatigue in people with progressive MS. METHODS: Six electronic databases (CINAHL, Cochrane Library, MEDLINE, PEDro, ProQuest, and Web of Science Core Collections) were searched for relevant articles up until November 2017. Randomized controlled trials and quasi-experimental studies that examined the effects of exercise, behavioral interventions, and rehabilitation on fatigue in people with progressive MS using self-reported fatigue outcome measures were included in this review. RESULTS: Eight exercise, two rehabilitation, and two behavioral interventions were investigated in the 13 articles included in this review. Heterogeneous effects were reported between studies, with only two exercise, one behavioral, and two rehabilitation interventions recording significant improvements in postintervention fatigue severity or impact. However, most studies were underpowered, only two used fatigue as the primary outcome, and only one specifically recruited participants with predefined levels of fatigue. CONCLUSIONS: Evidence from this review is inconclusive regarding the effectiveness of nonpharmacologic interventions in reducing the severity and impact of fatigue in progressive MS populations. Adequately powered randomized controlled trials are required to evaluate fatigue management interventions in people with progressive MS experiencing high levels of fatigue and using fatigue as the primary outcome.

Prevalence of fatigue and its association with clinical features in progressive and non-progressive forms of Multiple Sclerosis.

BACKGROUND: Fatigue is a complex and disabling symptom of Multiple Sclerosis (MS); however, there is conflicting evidence of the relationship between fatigue and clinical features of MS. Furthermore, few studies have considered these relationships specifically in a progressive MS population. AIMS: (1) estimate the prevalence of self-reported fatigue in people with MS; (2) evaluate the relationship between fatigue severity/impact and clinical features of MS; (3) compare the prevalence of fatigue, and the strength of relationship between fatigue severity/impact and clinical features of MS in progressive and non-progressive forms of MS. METHODS: An online survey was conducted to measure the severity (Fatigue Severity Scale (FSS)) and impact of self-reported fatigue (Modified Fatigue Impact Scale) in people with MS. The survey also contained questionnaires related to disability, quality of life, MS impact, anxiety and depression, cognition, and sleep quality. RESULTS: 412 people responded to the survey, of which 68.7% reported having fatigue (FSS ≥ 5). The prevalence of fatigue was significantly higher in participants with progressive MS (81%) in comparison to those with non-progressive forms of MS (64%, p = 0.01). Fatigue severity and impact were associated with quality of life, MS impact, anxiety, depression, cognition, and sleep quality in both progressive and non-progressive MS populations (p < 0.05). However, fatigue severity (r = 0.335) and impact (r = 0.391) were correlated with disability only in participants with non-progressive MS. CONCLUSION: Fatigue was more prevalent amongst participants with progressive MS. In addition, higher fatigue severity and impact were associated with greater physical, cognitive, and psychological impairment, although the strength of association between these outcomes was generally similar regardless of the type of MS.

Distal upper limb kinematics during functional everyday tasks.

Quantitative characterisation of upper limb motion allows the evaluation of the effect of pathology on functional task performance, potentially directing rehabilitation strategies. Movement patterns of the distal upper limb in healthy adults during functional tasks have not been extensively characterised. During five loaded functional tasks (drinking from a glass, pouring from a kettle, turning a handle, lifting a bag to a shelf, turning a key) the movement patterns were characterised using three-dimensional motion analysis with a minimal marker set in 16 healthy adults (10 M,6F, 27 (IQR:25-43)years). Joint angles reported include flexion/extension at the elbow and wrist, forearm supination/pronation and digits 2-5 metacarpophalangeal (MCP) joint flexion/extension. Additionally for the thumb the angle between the metacarpal of the thumb and the 2nd digit (Thumb base), the thumb MCP (Thumb MCP) and interphalangeal (Thumb IP) joint angles are presented. Durations of activities performed at self-selected comfortable speeds (3.36 (IQR:3.07,3.66)s turning a key to 6.20 (IQR:5.44,6.38)s drinking from a glass) are reported. The maximum joint angles used (median of participants' maxima) were 141° of elbow flexion, 116° forearm supination, 36° wrist extension, 56° Thumb base, 14° Thumb MCP flexion, 18° Thumb IP flexion, 85° MCP2-5 flexion. The tasks of drinking from a glass, lifting a bag to a shelf and turning a key appeared to have the least variation in performance, suggesting that these activities are better suited to be selected as standardized tasks for assessing the impact of pathology on movement than pouring from a kettle and turning a handle.