Characterizing fatigue phenotypes with other symptoms and clinically relevant outcomes among people with multiple sclerosis.

PURPOSE: Fatigue is a common symptom of multiple sclerosis (MS) and can adversely affect all aspect of quality of life. The etiology of fatigue remains unclear, and its treatments are suboptimal. Characterizing the phenotypes of fatigued persons with MS may help advance research on fatigue's etiology and identify ways to personalize fatigue interventions to improve quality of life. The purpose of this study was to identify fatigue phenotypes; examine phenotype stability overtime; and characterize phenotypes by health and function, social and environmental determinants, psychosocial factors, and engagement in healthy behaviors. METHODS: We conducted a longitudinal study over a 3-month period with 289 fatigued participants with MS. To identify fatigue phenotypes and determine transition probabilities, we used latent profile and transition analyses with valid self-report measures of mental and physical fatigue severity, the mental and physical impact of fatigue, depression, anxiety, and sleep quality. We used ANOVAs and effect sizes to characterize differences among phenotypes. RESULTS: The best fitting model included six subgroups of participants: Mild Phenotype, Mild-to-Moderate Phenotype, Moderate-to-Severe Phenotype, Severe Phenotype, Fatigue-dominant Phenotype, and Mental Health-dominant Phenotype. The transition analysis indicated that phenotypic membership was highly stable. Variables with a large eta squared effect size included environmental barriers, self-efficacy, and fatigue catastrophizing. CONCLUSION: These results indicate that the magnitude of fatigue experienced may be more important to consider than the type of fatigue when characterizing fatigue phenotypes. Future research should explore whether tailoring interventions to environmental barriers, self-efficacy, and fatigue catastrophizing reduce the likelihood of transitioning to a more severe phenotype.

Intervention Mediators in a Randomized Controlled Trial to Increase Physical Activity and Fatigue Self-management Behaviors Among Adults With Multiple Sclerosis.

BACKGROUND: People with multiple sclerosis (MS) often experience fatigue, which is aggravated by inactivity. Identifying mediators of changes in physical activity (PA) and fatigue self-management (FSM) behaviors could optimize future interventions that reduce the impact of MS fatigue. PURPOSE TO: examine the effects of telephone-delivered interventions on Social Cognitive Theory constructs and test whether these constructs mediated secondary outcomes of PA and FSM behaviors. METHODS: Participants with MS (n = 208; Mean age = 52.1; Female = 84.6%) were randomized into contact-control intervention (CC), PA-only intervention, and PA+FSM intervention. Step count (Actigraphy) and FSM behaviors as well as self-efficacy, outcome expectations, and goal setting for PA and FSM were measured at baseline, post-test (12 weeks), and follow-up (24 weeks). Path analyses using bias-corrected bootstrapped 95% confidence intervals (CI) determined whether constructs at post-test mediated behaviors at follow-up when adjusting for baseline measures. RESULTS: Path analysis indicated that PA-only (ß = 0.50, p < .001) and PA+FSM interventions (ß = 0.42, p < .010) had an effect on goal setting for PA, and that PA + FSM intervention had an effect on self-efficacy for FSM (ß = 0.48, p = .011) and outcome expectations for FSM (ß = 0.42, p = .029). Goal setting for PA at post-test mediated the effects of PA-only (ß = 159.45, CI = 5.399, 371.996) and PA + FSM interventions (ß = 133.17, CI = 3.104, 355.349) on step count at follow-up. Outcome expectations for FSM at post-test mediated the effects of PA + FSM intervention on FSM behaviors at follow-up (ß = 0.02, CI = 0.001, 0.058). CONCLUSIONS: Goal setting for PA and outcome expectations for FSM may be important constructs to target in telephone-delivered interventions designed to reduce the impact of MS fatigue. TRIAL REGISTRATION: Clinicaltrials.gov (NCT01572714).

Beyond supervised therapy: Promoting behavioral changes in people with MS.

A critical aspect of many rehabilitation interventions for people with multiple sclerosis (MS) is incorporating strategies that support behavior change. The main purpose of this topical review was to summarize recent randomized clinical trials (RCTs) of rehabilitation interventions in which participants learn and apply skills or engage in healthy behaviors. The Capability, Opportunity, Motivation, and Behavior (COM-B) framework was used to broadly classify behavior-change strategies. The included RCTs varied widely in terms of dosing, delivery format, and types of interventionist. Commonly used behavior-change strategies include education, persuasion, and training. We recommend that researchers and clinicians use frameworks like Behavior Change Wheel and Behavior Change Technique Taxonomy to describe and classify intervention strategies used to promote behavior change. We also recommend more sophisticated RCTs be conducted (e.g. sequential multiple assignment randomized trial and three-arm RCTs) to better understand ways of promoting behavior change in rehabilitation interventions.

Randomized Controlled Trial of a Telephone-Delivered Physical Activity and Fatigue Self-management Interventions in Adults With Multiple Sclerosis.

OBJECTIVE: To compare the effectiveness of telephone-delivered interventions on fatigue, physical activity, and quality of life outcomes in adults with multiple sclerosis (MS). DESIGN: A single-blinded, randomized controlled trial. Participants were randomized to contact-control intervention (CC), physical activity-only intervention (PA-only), and physical activity plus fatigue self-management intervention (FM+). Outcomes were measured at baseline (2wk prerandomization), posttest (14wk postrandomization), and follow-up (26wk postrandomization). SETTING: Telephone-delivered in Midwest and Northeast regions of the United States. PARTICIPANTS: Inactive adults with MS (N=208) and moderate-to-severe fatigue. INTERVENTIONS: Three or 6 group teleconferences followed by 4 individually tailored phone calls delivered during 12 weeks. An occupational therapist and research assistant delivered the teleconferences and tailored phone calls, respectively. MAIN OUTCOME MEASURES: Primary outcomes were self-report fatigue and physical activity measured with the Fatigue Impact Scale and Godin Leisure-Time Exercise Questionnaire, respectively. Secondary outcomes included quality of life measured with the Multiple Sclerosis Impact Scale and moderate-to-vigorous exercise and step count measured with an accelerometer. RESULTS: Linear mixed effects models showed FM+ significantly improved self-reported fatigue (ß=-11.08; P=.03) and physical activity (ß=0.54; P=.01) compared with CC at posttest. However, FM+ had nonsignificant differences compared with PA-only on self-report fatigue (ß=-1.08, P=.84) and physical activity (ß=0.09; P=.68) at posttest. PA-only had significant improvements compared with CC on moderate-to-vigorous exercise (ß=0.38; P=.02) at posttest and step count at posttest (ß=1.30; P<.01) and follow-up (ß=1.31; P=.01) measured with an accelerometer. FM+ and PA-only had nonsignificant differences compared with CC on quality of life. CONCLUSIONS: Group teleconferences followed by tailored phone calls have a small yet statistically significant effect in promoting physical activity and reducing fatigue impact in people with MS.

Wellness and multiple sclerosis: The National MS Society establishes a Wellness Research Working Group and research priorities.

BACKGROUND: People with multiple sclerosis (MS) have identified "wellness" and associated behaviors as a high priority based on "social media listening" undertaken by the National MS Society (i.e. the Society). OBJECTIVE: The Society recently convened a group that consisted of researchers with experience in MS and wellness-related research, Society staff members, and an individual with MS for developing recommendations regarding a wellness research agenda. METHOD: The members of the group engaged in focal reviews and discussions involving the state of science within three approaches for promoting wellness in MS, namely diet, exercise, and emotional wellness. RESULTS: That process informed a group-mediated activity for developing and prioritizing research goals for wellness in MS. This served as a background for articulating the mission and objectives of the Society's Wellness Research Working Group. CONCLUSION: The primary mission of the Wellness Research Working Group is the provision of scientific evidence supporting the application of lifestyle, behavioral, and psychosocial approaches for promoting optimal health of mind, body, and spirit (i.e. wellness) in people with MS as well as managing the disease and its consequences.

Randomized controlled pilot study of customized pamphlets to promote physical activity and symptom self-management in women with multiple sclerosis.

OBJECTIVE: Investigate the feasibility and potential efficacy of a customized print-based intervention to promote physical activity and symptom self-management in women with multiple sclerosis. DESIGN: A randomly allocated two-group repeated measures design, with a delayed-treatment contact group serving as the control. Participants were randomized to receive the intervention immediately (n =14) or receive it at week 12 (n =16). Outcome measures were administered at weeks 1, 12, and 24. SETTING: Community-based in metropolitan area. SUBJECTS: Thirty women with multiple sclerosis. INTERVENTION: Prescribing a home-exercise program and following up with customized pamphlets, which are matched to participants' stage of readiness to change physical activity behavior and physical activity barriers (e.g. encouraging self-management of symptoms). MAIN MEASURES: Physical Activity and Disability Survey-revised, Godin Leisure-Time Exercise Questionnaire, SF-12, Symptoms of Multiple Sclerosis Scale, and 6-minute walk test. RESULTS: Intent-to-treat analyses using mixed multivariate analysis of variance (MANOVA) were conducted on (1) physical activity levels and (2) health and function outcomes. The mixed MANOVAs for physical activity levels and health and function outcomes indicated significant improvements in the immediate group compared with the delayed group (i.e. condition by time interaction was significant, Wilks' λ = 0.59, F(2, 27) = 9.31, P = 0.001 and Wilks' λ = 0.70, F(4, 25) = 2.72, P = 0.052, respectively). The intervention had moderate to large effect sizes in improving physical activity levels (d = 0.63 to 0.89), perceptions of physical function (d = 0.63), and 6-minute walk test (d=0.86). CONCLUSION: This pilot study indicates that a customized print-based intervention shows promise in improving physical activity levels and health and function in women with multiple sclerosis.

A formative evaluation of customized pamphlets to promote physical activity and symptom self-management in women with multiple sclerosis.

Inactivity is a prevalent problem in the population affected with multiple sclerosis (MS). Thus, there is a need to develop and test physical activity (PA) interventions that can be widely disseminated. We conducted a formative evaluation as part of a randomized controlled trial of a pamphlet-based PA intervention among 30 women with MS. Pamphlets were customized to sub-sets of participants who shared similar symptoms and barriers to PA. Mixed methods were used to examine the intervention's influence on self-efficacy, social support, processes of change and stages of change placement, as well as explore participants' perceived barriers, motivators and strategies for engaging in a PA program. Results indicated that the intervention group significantly improved stages of change placement (F = 16.64, P < 0.01) and social support (F = 4.08, P = 0.05) in comparison to the control group. Fatigue, pain and lack of time were the commonly cited barriers to engage in the PA program; whereas the pamphlets, phone calls and action planning were cited as motivators. Participants used fatigue management strategies, enlisted social support and modified their environment to routinely engage in the PA program. Strategies were identified to improve the PA intervention in future research.

Factors influencing how informal caregivers of people with multiple sclerosis access and use a curated intervention website: Analysis from an RCT.

Objective: Healthcare consumers and providers are increasingly turning to digital solutions, such as curated websites. Knowing who accesses/benefits from these may improve design and development. This study investigated website usage of informal caregivers of people with multiple sclerosis and shifts in outcome plausibly associated with usage. Methods: Secondary analysis of data from a randomized clinical trial of 148 caregivers compared effectiveness of a website + tele-coaching to a website only intervention for caregivers. Groupwise differences in means/proportions were tested using t-tests and chi-square. Modified Poisson regression with a robust variance estimator and ordinal logistic regression tested the relationship between group and likelihood of website log-in. Ordinal logistic regression models examined whether caregiver characteristics were associated with website use. Generalized estimating equations (GEE) with an autoregressive correlation structure modeled the relationship between website usage and outcomes. Results: Females were more likely to access the website than males (60% vs. 43%; p = 0.05). Though not statistically significant, a possible association (POR: .85, 95% CI: .69, 1.03) between caregiver burden and website access emerged; caregivers experiencing highest levels of burden appeared less likely to engage. Usage patterns differed by treatment arm: the website-only group accessed the Caring for yourself topic significantly more (61.67% vs. 38.33%: p = .04) with similar, but insignificant, trends for other topics. Conclusions: Clinicians can be confident referring females with moderate levels of burden to website-based interventions. By contrast, male caregivers and those experiencing high levels of burden may be less likely to access these resources, pointing to the need for alternative interventions. Trial Registration: Clinicaltrials.gov, registration number: NCT0466208.

Virtual versus usual in-office care for multiple sclerosis: The VIRTUAL-MS multi-site randomized clinical trial study protocol.

BACKGROUND: Multiple sclerosis (MS) affects nearly 1 million people and is estimated to cost $85.4 billion in the United States annually. People with MS have significant barriers to receiving care and telemedicine could substantially improve access to specialized, comprehensive care. In cross-sectional analyses, telemedicine has been shown to be feasible, have high patient and clinician satisfaction, reduce patient costs and burden, and enable a reasonable assessment of disability. However, no studies exist evaluating the longitudinal impact of telemedicine care for MS. Here we describe the study protocol for VIRtual versus UsuAL In-office care for Multiple Sclerosis (VIRTUAL-MS). The main objective of the study is to evaluate the impact of telemedicine for MS care on: patient clinical outcomes, economic costs, patient, and clinician experience. METHODS: This two-site randomized clinical trial will enroll 120 adults with a recent diagnosis of MS and randomize 1:1 to receive in-clinic vs. telemedicine care for 24 months. The primary outcome of the study is worsening in any one of the four Multiple Sclerosis Functional Composite 4 (MSFC4) measures at 24 months. Other study outcomes include patient and clinician satisfaction, major healthcare costs, Expanded Disability Status Scale, treatment adherence, and digital outcomes. CONCLUSION: The results of this study will directly address the key gaps in knowledge about longitudinal telemedicine-enabled care in an MS population. It will inform clinical care implementation as well as design of trials in MS and other chronic conditions. TRIAL REGISTRATION: NCT05660187.

Psychometric Properties and Clinical Utility of the Distress Thermometer in Caregivers of Persons With Multiple Sclerosis.

BACKGROUND: Caregivers of persons with multiple sclerosis (MS) report high levels of distress. The National Comprehensive Cancer Network Distress Thermometer (DT) is used extensively with patients with cancer and their caregivers but has not been tested in nononcology caregivers. The purpose of this study was to examine the psychometric properties and clinical utility of the barometer portion of the DT in caregivers of persons with MS. METHODS: A secondary analysis was performed of data from a randomized trial comparing the effectiveness of 2 interventions aimed at reducing psychological outcomes associated with caregiving. The DT and the 4-item Patient-Reported Outcomes Measurement Information System Anxiety and Depression scales, which were administered at baseline, were used for all analyses. Construct validity (known groups) and convergent validity (interscale correlations) were evaluated. Receiver operating characteristic curve analysis was used to evaluate clinical diagnostic test evaluation. RESULTS: The DT had good construct validity supported by strong correlations for known-groups analyses and good convergent validity (r = 0.70-0.72). The DT also demonstrated good discrimination for anxiety (area under the curve [AUC] = 0.83) and depression (AUC = 0.80). The optimal screening cut point on the DT was 4 for anxiety and 5 for depression. CONCLUSIONS: The barometer portion of the DT demonstrates good psychometric properties and clinical utility in caregivers of persons with MS. This is the first examination of the DT in MS care partners.

Effect of 2-Arm Intervention on Emotional Outcomes in Informal Caregivers of Individuals With Multiple Sclerosis: A Randomized Pilot Study Trial.

BACKGROUND: Caregivers of people with multiple sclerosis (MS) report poor emotional outcomes yet few interventions have been tested. The goal of this study was to compare the effectiveness of a remotely delivered intervention with 2 arms (ie, website and telecoaching vs website only) aimed at reducing depression, anxiety, stress, and distress in informal caregivers of individuals with MS. METHODS: From March 2021 through August 2021, 151 care-givers were enrolled in the study. The intervention occurred over a 4-month period. The website plus telecoaching arm received (a) a monthly coaching session focused on information, skill building, and support that was delivered by a licensed social worker via videoconference or telephone, and (b) had access to a study-designed website for caregivers of individuals with MS. The website-only arm did not receive coaching sessions and had the same website access. Data were obtained at baseline, immediately after the intervention period, and 6 weeks after the intervention. RESULTS: A linear mixed-effects model using an autoregressive covariance structure was used. It showed that the group by time interaction was statistically significant for the overall composite emotion score (depression, anxiety, stress) (P = .037) and the stress subscale score (P = .047), and it indicated that the website plus telecoaching arm demonstrated greater effectiveness at reducing the overall composite emotion and stress subscale scores. CONCLUSIONS: Use of a remotely delivered psychoeducational intervention that included individual coaching sessions as well as website access demonstrated preliminary efficacy in improving emotional outcomes in caregivers of individuals with MS. Further testing of the intervention with a larger sample is recommended.

Fatigue as an Understudied Barrier to Participation in Life Roles.

Fatigue is one of the most burdensome and disabling symptoms in numerous acute and chronic conditions and is associated with reduced participation in all aspects of daily life, for example, parenting, employment, and socialization. Historically, occupational practitioners played key roles in fatigue management by creating and implementing interventions. The American Occupational Therapy Foundation convened a Planning Grant Collective workshop with the goal to develop collaborative research ideas and proposals to advance the understanding and management of fatigue. Participants from occupational therapy and other disciplines, with expertise with fatigue or who were conducting research on fatigue, participated in a 3-day virtual workshop. Four main topics emerged: implementation science, treatment taxonomy, trial design and comparative effectiveness, and phenotyping. This white paper describes the proceedings, summarizes the discussions, and outlines recommendations from the PGC workshop on fatigue.

Randomized controlled trial of a teleconference fatigue management plus physical activity intervention in adults with multiple sclerosis: rationale and research protocol.

BACKGROUND: Chronic fatigue and inactivity are prevalent problems among individuals with multiple sclerosis (MS) and may independently or interactively have detrimental effects on quality of life and ability to participate in life roles. However, no studies to date have systematically evaluated the benefits of an intervention for both managing fatigue and promoting physical activity in individuals with MS. This study involves a randomized controlled trial to examine the effectiveness of a telehealth intervention that supports individuals with MS in managing fatigue and increasing physical activity levels. METHODS/DESIGN: A randomly-allocated, three-parallel group, time-series design with a social support program serving as the control group will be used to accomplish the purpose of the study. Our goal is to recruit 189 ambulatory individuals with MS who will be randomized into one of three telehealth interventions: (1) a contact-control social support intervention, (2) a physical activity-only intervention, and (3) a physical activity plus fatigue management intervention. All interventions will last 12 weeks and will be delivered entirely over the phone. Our hypothesis is that, in comparison to the contact-control condition, both the physical activity-only intervention and the physical activity plus fatigue management intervention will yield significant increases in physical activity levels as well as improve fatigue and health and function, with the physical activity plus fatigue management intervention yielding significantly larger improvements. To test this hypothesis, outcome measures will be administered at Weeks 1, 12, and 24. Primary outcomes will be the Fatigue Impact Scale, the Godin Leisure-Time Exercise Questionnaire (GLTEQ), and Actigraph accelerometers. Secondary outcomes will include the SF-12 Survey, Mental Health Inventory, Multiple Sclerosis Impact Scale, the Community Participation Indicator, and psychosocial constructs (e.g., self-efficacy). DISCUSSION: The proposed study is novel, in that it represents a multi-disciplinary effort to merge two promising lines of research on MS: fatigue management and physical activity promotion. Collectively, the proposed study will be the largest randomized controlled trial to examine the effects of a lifestyle physical activity intervention in people with MS. TRIAL REGISTRATION: NCT01572714.

Disentangling self-reported fatigue, depression, and cognitive impairment in people with multiple sclerosis.

BACKGROUND: Fatigue is a common problem among people with multiple sclerosis (MS) and can have a negative effect on mental, physical, and social function. Self-reported measures of MS fatigue are often operationalized as a multi-dimensional symptom. However, questions remain about how best to account for the multi-dimensional aspects of self-reported fatigue and whether these aspects are distinct entities. Thus, the purpose of this study was to explore the overlap and distinctions between self-reported measures of the severity and impact of fatigue, between mental and physical fatigue, and between mental fatigue, depressive symptoms, and cognitive impairment. METHODS: An observational study was conducted with 289 participants with MS . The questionnaires were the Unidimensional Fatigue Impact Scale (UFIS), the Chalder Fatigue Scale (CFS), the Fatigue Scale for Motor and Cognitive Functions (FSMC), the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNSQ), and the Quality of Life in Neurological Disorders short form for depression (Neuro-QoL). Spearman's correlation coefficient was used to examine the bivariate correlations between composite and subscale scores. Exploratory structural equation modeling (ESEM) was used to determine the factor structure under a pre-specified number of factors to retain in the modeling of multiple items across questionnaires and examine model fit. Subsequently for poor fitting models in an iterative procedure to determine a better fitting multidimensional model, we posited a bifactor confirmatory factor analysis model. RESULTS: The bivariate correlation analysis revealed that subscales from the same questionnaire measuring different aspects of fatigue had the highest correlations (r = 0.61-0.68), subscales from different questionnaires measuring the same aspect of fatigue had the next highest correlations (r = 0.43-0.60), and subscales from different questionnaires measuring different aspects of fatigue had the lowest correlations (r = 0.34-0.40). Bifactor models with a general fatigue factor and subdomains pertaining to impact, severity, and mental and physical fatigue had relatively good model fits compared to models omitting the subdomains. However, an ESEM model using subscales from the CFS and FSMC fit poorly and did not adequately identify separate factors for mental and physical fatigue. An ESEM model with separate factors for self-reported mental fatigue, depressive symptoms, and cognitive impairment was a good fit. CONCLUSIONS: The working study hypothesis that fatigue constructs would be moderately correlated yet distinct entities was generally supported by the results of the study. However, we found that our hypothesized separation into a latent dimension existed only when the items or subscales came from the same questionnaire, in which case their level of specificity in terms of target, action, context, and time elements for measuring fatigue were consistent. The implications for the principle of compatibility in measuring self-reported MS fatigue are discussed.

Predictors of fatigue self-management behaviors in adults with multiple sclerosis.

BACKGROUND: Fatigue is one of the most common and disabling symptoms in people with multiple sclerosis (MS). Fatigue self-management behaviors may be effective in reducing the impact of fatigue in people with MS. However, few studies have examined the factors that influence engagement in fatigue self-management behaviors. OBJECTIVE: Identify factors that directly and indirectly influence fatigue self-management behaviors. METHODS: Participants with MS (n = 287) completed online questionnaires at baseline and 6-weeks. Guided by the Self- and Family Management Framework, we examined the influence of health status, resources and environment, healthcare utilization, and self-management processes on fatigue self-management behaviors at 6-weeks. Multiple regression and path analyses were conducted. RESULTS: The final regression model variables accounted for 41.58% of the variance in fatigue self-management behaviors, which included outcome expectations (ß= 0.287), disability (ß= 0.265), environmental barriers (ß= 0.188), self-efficacy (ß= 0.153), symptom severity (ß= 0.113), living in an urban community (ß= -0.108), and living alone (ß= 0.103). Path analysis indicated that outcome expectations may mediate the relationship between disability levels and fatigue self-management behavior. CONCLUSIONS: Health status (i.e., disability and symptom severity), environmental factors (e.g., living situation), and self-management processes (i.e., self-efficacy and outcome expectations) may play an important role in influencing engagement in fatigue self-management behaviors.

Response heterogeneity in a randomized controlled trial of telerehabilitation interventions among adults with multiple sclerosis.

INTRODUCTION: Telerehabilitation may be effective on average but is not equally effective among all people with multiple sclerosis (MS). Thus, the purpose of this secondary analysis of a randomized controlled trial was to explore whether baseline characteristics of participants with MS influence fatigue and physical activity outcomes of three telerehabilitation interventions. METHODS: Participants were randomized to contact-control intervention (CC), physical activity-only intervention (PA-only), and physical activity plus fatigue self-management intervention (FM+). The 12-week interventions were delivered over the phone. Sociodemographic (age and income), clinical (comorbidities, mental function and physical function), psychosocial (self-efficacy, outcome expectations and goal-setting), and behavioural baseline characteristics (step count and fatigue self-management behaviors) were used in a moderated regression analysis and a responder analysis to examine their influence on the Fatigue Impact Scale (FIS) and Godin Leisure-Time Exercise Questionnaire (GLTEQ) at post-test (i.e. immediately post-interventions). RESULTS: No interactions terms were statistically significant in the moderation analysis. However, the responder analysis showed that baseline psychosocial characteristics and mental function were significantly different (p < 0.05) between responders and non-responders. Specifically, non-responders on the FIS at post-test in the PA-only intervention had significantly lower baseline scores in goal setting for engaging in fatigue self-management behaviours. Also, non-responders on the GLTEQ at post-test in the FM+ intervention had significantly worse baseline scores in mental function. DISCUSSION: Further research is needed to understand the complex relationship among baseline characteristics, telerehabilitation and response heterogeneity. We discuss how research on examining response heterogeneity may be advanced by conducting mega-clinical trials, secondary analyses of big data, meta-analyses and employing non-traditional research designs. TRIAL REGISTRATION: Clinicaltrials.gov (NCT01572714).

Randomized trial of a teleconference-delivered fatigue management program for people with multiple sclerosis.

BACKGROUND: Previous studies support the efficacy and effectiveness of face-to-face group-based fatigue management education for people with multiple sclerosis (MS). Nevertheless, many people are unable to access these programs due to environmental barriers. OBJECTIVES: To test the efficacy and effectiveness of a group-based, teleconference-delivered fatigue management program for people with MS. METHODS: A randomly allocated two-group time series design with a wait-list control group was used. In total 190 participants were allocated (94 intervention, 96 wait-list control). Primary outcomes (fatigue impact, fatigue severity, health-related quality of life (HRQOL)) were measured before, immediately after, at 6 weeks, 3 months, and 6 months post. Secondary outcome (self-efficacy) was measured at the same points. Effectiveness (intent-to-treat) and efficacy (per protocol) analyses were conducted. RESULTS: The program was more effective and efficacious than control for reducing fatigue impact but not fatigue severity. Before and after comparisons with the pooled sample demonstrated efficacy and effectiveness for fatigue impact, fatigue severity, and 6 of 8 HRQOL dimensions. Changes were maintained for 6 months with small to moderate effect sizes. CONCLUSION: The results offer strong support for the viability of teleconference-delivered fatigue management education for enabling people with MS to manage this disabling symptom.

Correlates of stages of change for physical activity in adults with multiple sclerosis.

The Transtheoretical Model (TTM) is commonly used to understand physical activity (PA) behavior in the general population; however, few researchers have explored its relevance for persons with multiple sclerosis (MS). We examined the relative importance of health (symptoms and mobility impairments) and TTM constructs (behavioral and cognitive processes of change) in influencing stages of change placement for PA in a sample of 303 persons with MS using discriminant function analysis. The overall accuracy of predicting stages of change was 58.75%. Behavioral (r(2) = .35) and cognitive processes (r(2) = .17) accounted for the most variance, followed by mobility (r(2) = .11) and self-efficacy (r(2) = .05). Results provide support for evaluating whether TTM-based interventions can promote PA in adults with MS.

Psychoeducational Interventions for Caregivers of Persons With Multiple Sclerosis: Protocol for a Randomized Trial.

BACKGROUND: Of the approximately 1 million people living with multiple sclerosis in the United States, more than half receive informal, unpaid care or support from family or friends (caregivers). These caregivers report high levels of stress, anxiety, and negative emotions. Few researchers have conducted psychoeducational interventions for these caregivers. OBJECTIVE: This paper presents a protocol for a randomized clinical trial that aims to test the efficacy of two interventions for improving stress, anxiety, depression, and negative emotions for caregivers of persons with multiple sclerosis. METHODS: Participants included any self-identified family or friend caregiver of a person with multiple sclerosis. Data collection began in April 2021 and is expected to continue until November 2021. Participants will be randomized to receive either a website-only or a website-coaching intervention delivered for 6 weeks. Data will be collected at baseline, 6 weeks after baseline (after delivery of intervention), and 6 weeks later. RESULTS: The protocol was approved by the institutional review board of the Case Western Reserve University on January 21, 2021 (protocol 20201484). As of May 2021, 66 participants were enrolled. CONCLUSIONS: Our findings will have implications for identifying the efficacy of two types of interventions developed for caregivers of persons with multiple sclerosis to reduce negative psychological outcomes associated with caregiving. TRIAL REGISTRATION: ClinicalTrials.gov NCT04662008; http://clinicaltrials.gov/ct2/show/NCT04662008. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30617.

Utilization of health promotion and wellness services among middle-aged and older adults with multiple sclerosis in the mid-west US.

Routine engagement in healthy behaviors may improve quality of life in older adults with chronic disabling conditions, such as multiple sclerosis (MS). However, older adults with chronic conditions may face many barriers to engaging in healthy behaviors. Health promotion and wellness services may help older adults with chronic conditions engage in healthy behaviors. Thus, the purpose of this study was to identify factors associated with the use of and unmet needs for heath promotion services among middle-aged and older adults with MS. Data from a cross-sectional telephone survey of individuals aging with MS in the mid-west USA were used for this study (n = 1282). A multinomial regression model was used to identify variables associated with the utilization of health promotion services. A logistic regression model was used to identify variables associated with unmet needs for these services. Females (OR = 1.51; CI: 1.13, 2.00), high school graduates (OR = 1.77; CI: 1.34, 2.34) and people who reported no problems with mobility or balance (OR = 1.68; CI: 1.12, 2.51) were more likely to utilize health promotion and wellness services. Factors that increased the likelihood of reporting an unmet need for these services were being female (OR = 2.34; CI: 1.56, 3.51), greater than a high school education (OR = 1.58; CI: 1.14, 2.20), not being married (OR = 1.79; CI: 1.31, 2.43), having inadequate income (OR = 1.83; CI: 1.31, 2.56), experiencing pain (OR = 1.96; CI: 1.34, 2.87) and reporting less ability to do everyday activities now compared with 1 year ago (OR = 2.13; CI: 1.16, 3.92). To avoid widening the health-disparities gap, future research needs to explore strategies that promote utilization of health promotion services among all middle-aged and older adults with MS.