BACKGROUND:Fatigue is one of the most disabling symptoms reported by people with multiple sclerosis. Although behavioural and pharmacological interventions might be partly beneficial, their combined effects have not been evaluated for multiple sclerosis fatigue, or examined with sufficient consideration of characteristics that might affect treatment response. In this comparative effectiveness research trial, we compared the effectiveness of cognitive behavioural therapy (CBT), modafinil, and their combination for treating multiple sclerosis fatigue. METHODS:This randomised, analyst-blinded, parallel-arm, comparative effectiveness trial was done at two universities in the USA. Adults (aged ≥18 years) with multiple sclerosis and problematic fatigue (Fatigue Severity Scale [FSS] score ≥4) were randomly assigned (1:1:1), using a web-based treatment assignment system with minimisation, to receive CBT, modafinil, or both for 12 weeks. Statisticians were masked to group assignment, but participants, study neurologists, CBT interventionalists, and coordinators were not masked to treatment assignment. The primary outcome was the change in Modified Fatigue Impact Scale (MFIS) from baseline to 12 weeks, assessed using multiple linear regression, adjusted for age, sex, study site, anxiety, pain, baselines MFIS score, and physical activity. Analyses were done by intent to treat. The trial was registered with clinicaltrials.gov, NCT03621761, and is completed. FINDINGS:Between Nov 15, 2018, and June 2, 2021, 336 participants were randomly assigned treatment (114 assigned to CBT, 114 assigned to modafinil, and 108 assigned to combination therapy). At 12 weeks, CBT (n=103), modafinil (n=107), and combination therapy (n=102) were associated with clinically meaningful within-group MFIS reductions of 15·20 (SD 11·90), 16·90 (15·90), and 17·30 (16·20) points, respectively. Change in MFIS scores from baseline to 12 weeks did not differ between groups: relative to combination therapy, the adjusted total mean difference in MFIS change score was 1·88 (95% CI -2·21 to 5·96) for CBT and 1·20 (-2·83 to 5·23) for modafinil. Most common adverse events for modafinil-containing treatment groups included insomnia (eight [7%] for modafinil and eight [7%] for combination therapy) and anxiety (three [3%] for modafinil and nine [8%] for combination therapy). INTERPRETATION:Modafinil, CBT, and combination therapy were associated with similar reductions in the effects of multiple sclerosis fatigue at 12 weeks. Combination therapy was not associated with augmented improvement compared with the individual interventions. Further research is needed to determine whether effects of these interventions on multiple sclerosis-related fatigue is influenced by sleep hygiene and sleepiness. No serious adverse events related to the study drug were encountered. FUNDING:Patient-Centered Outcomes Research Institute and National Multiple Sclerosis Society.

IMPORTANCE Racial, ethnic, and geographic differences in multiple sclerosis (MS) are important factors to assess when determining the disease burden and allocating health care resources.OBJECTIVE To calculate the US prevalence of MS in Hispanic, non-Hispanic Black (hereafter referred to as Black), and non-Hispanic White individuals (hereafter referred to as White) stratified by age, sex, and region.DESIGN, SETTING, AND PARTICIPANTS A validated algorithm was applied to private, military, and public (Medicaid and Medicare) administrative health claims data sets to identify adult cases of MS between 2008 and 2010. Data analysis took place between 2019 and 2022. The 3-year cumulative prevalence overall was determined in each data set and stratified by age, sex, race, ethnicity, and geography. The insurance pools included 96 million persons from 2008 to 2010. Insurance and stratum-specific estimates were applied to the 2010 US Census data and the findings combined to calculate the 2010 prevalence of MS cumulated over 10 years. No exclusions were made if a person met the algorithm criteria.MAIN OUTCOMES AND MEASUREMENTS Prevalence of MS per 100 000 US adults stratified by demographic group and geography. The 95% CIs were approximated using a binomial distribution.RESULTS A total of 744781 persons 18 years and older were identified with MS with 564426 cases (76%) in females and 180 355 (24%) in males. The median age group was 45 to 54 years, which included 229 216 individuals (31%), with 101 271 aged 18 to 24 years (14%), 158 997 aged 35 to 44 years (21%), 186 758 aged 55 to 64 years (25%), and 68 539 individuals (9%) who were 65 years or older. White individuals were the largest group, comprising 577725 cases (77%), with 80 276 Black individuals (10%), 53 456 Hispanic individuals (7%), and 33 324 individuals (4%) in the non-Hispanic other category. The estimated 2010 prevalence of MS per 100 000 US adults cumulated over 10 years was 161.2 (95% CI, 159.8-162.5) for Hispanic individuals (regardless of race), 298.4 (95% CI, 296.4-300.5) for Black individuals, 374.8 (95% CI, 373.8-375.8) for White individuals, and 197.7 (95% CI, 195.6-199.9) for individuals from non-Hispanic other racial and ethnic groups. During the same time period, the female to male ratio was 2.9 overall. Age stratification in each of the racial and ethnic groups revealed the highest prevalence of MS in the 45-to 64-year-old age group, regardless of racial and ethnic classification. With each degree of latitude, MS prevalence increased by 16.3 cases per 100 000 (95% CI, 12.7-19.8; P < .001) in the unadjusted prevalence estimates, and 11.7 cases per 100 000 (95% CI, 7.4-16.1; P < .001) in the direct adjusted estimates. The association of latitude with prevalence was strongest in women, Black individuals, and older individuals.CONCLUSIONS AND RELEVANCE This study found that White individuals had the highest MS prevalence followed by Black individuals, individuals from other non-Hispanic racial and ethnic groups, and Hispanic individuals. Inconsistent racial and ethnic classifications created heterogeneity within groups. In the United States, MS affects diverse racial and ethnic groups. Prevalence of MS increases significantly and nonuniformly with latitude in the United States, even when adjusted for race, ethnicity, age, and sex. These findings are important for clinicians, researchers, and policy makers.

BACKGROUND: The National Multiple Sclerosis Society (NMSS) strives to ensure that people affected by multiple sclerosis (MS) can live their best lives. This mission is reflected in the Society's strategic plan, which establishes the roadmap for the Society's continued commitment to a world free of MS. OBJECTIVE: The purpose of this article is to add to the understanding of both the scope and complexity of the impact of MS and MS-related supports on quality of life (QOL). METHODS: A national sample of people with MS (n = 748) participated in the study by completing validated surveys assessing their QOL, physical and mental health, MS self-efficacy, resilience, participation in NMSS, perceived stress, emotional support, and social roles and activities. A path model was used to examine how the frequently identified MS QOL predictors, including demographic, MS, psychosocial, and physical functional status variables relate to each other and to QOL. RESULTS: The model exhibited reasonable model fit with hypothesized paths being statistically significant and in the hypothesized direction. CONCLUSION: Findings revealed that the relationships among mental health, demographic factors, overall MS experiences, QOL, NMSS participation, and resonance with the mission of the NMSS are complex, highly nuanced, and yet strongly correlated. More importantly, the study highlights the strong influence of variables that are more readily amenable to change through programmatic and clinical intervention, and active self-management and participation.

Background and Objectives A recent report estimated that approximately 1 million adults were living with multiple sclerosis (MS) in the United States. Although MS is rarely the direct cause of death, its debilitating effects on normal body functions can result in considerable disruption to daily living and life roles including work, physical independence, mobility, social interaction, and participation in leisure activities. This study estimated the total economic burden of MS in the United States in 2019. Methods This study used a prevalence-based approach to estimate the national economic burden of MS. Claims from 3 sources (Medicare Current Beneficiary Survey, Medicare Standard Analytical File, and Optum de-identified Normative Health Information System) were used to obtain direct costs and a survey was developed to collect indirect costs (e.g., labor market productivity losses, costs of paid and unpaid caregivers, home modification) from 946 patients with MS (PwMS). Direct medical costs reflected the difference in the total average annual amount paid for PwMS vs matched controls without MS. Future earnings loss due to premature death attributable to MS was calculated using Centers for Disease Control and Prevention mortality data and Medicare claims data. Results The estimated total economic burden was $85.4 billion, with a direct medical cost of $63.3 billion and indirect and nonmedical costs of $22.1 billion. Retail prescription medication (54%); clinic-administered drugs, medication, and administration (12%); and outpatient care (9%) were the 3 largest components of the direct costs. The average excess per-person annual medical costs for PwMS was $65,612; at $35,154 per person, disease-modifying therapies (DMTs) accounted for the largest proportion of this cost. The cost per DMT user ranged from $57,202 to $92,719, depending on sex-age strata. The average indirect and nonmedical costs were $18,542 per PwMS and $22,875 per PwMS if caregivers' costs were included. Lost earnings due to premature death, presenteeism, and absenteeism losses were the largest indirect cost components. Discussion MS is a costly chronic disease, with direct costs of prescription drugs and indirect productivity loss being important cost drivers. Our findings suggested that the burden of MS in the United States has been underestimated.

BackgroundMultiple sclerosis adult day programs (MSADPs) offer life-enhancing services for individuals and informal caregivers affected by multiple sclerosis (MS), including medical care, rehabilitation therapies, nutrition therapy, cognitive training, tailored education, exercise programs, and social interaction. The purpose of this study was to examine the effects of MSADPs on health-related quality of life (HRQOL) and health care utilization of persons with MS and HRQOL and well-being of informal caregivers.MethodsUsing a quasi-experimental design, outcomes between baseline and 1-year follow-up in persons with MS and informal caregivers who used MSADP services and a comparison group of similar persons with MS and caregivers who did not use MSADP services were compared. For persons with MS, outcomes included standardized measures of physical and mental HRQOL and health care utilization. For caregivers, outcomes included physical and mental HRQOL and well-being. Changes in outcomes between baseline and follow-up were examined using propensity score-weighted difference-in-differences regression analysis.ResultsFor persons with MS, MSADP use had a significant positive effect on 12-Item Short Form Health Survey physical component scores, although the difference was not clinically meaningful. Use of MSADPs did not have effects on any other outcomes for persons with MS or caregivers.ConclusionsUse of MSADPs did not show a clinically meaningful effect on HRQOL for persons with MS or informal caregivers. The MSADPs do not seem to offer sustained benefits to persons with MS or caregivers, but the possibility of initial short-term benefits cannot be ruled out.

Background: Multiple sclerosis (MS) is the most common chronic neurologic disease of young adults, placing a heavy burden on patients, families, and the healthcare system. Ongoing surveillance of the incidence and prevalence of MS is critical for health policy and research, but feasible options are limited in the United States and many other countries. We investigated the feasibility of monitoring the prevalence of MS using a large national telephone survey of the adult US population. Methods: We developed questions to estimate the lifetime prevalence and age of onset of MS using the US-based Behavioral Risk Factor Surveillance System (BRFSS) and piloted these questions in 4 states (MN, RI, MD, and TX). There was a total of 45,198 respondents aged 18 years and above. Analyses investigated individual state and combined prevalence estimates along with health-related comorbidities and limitations. MS prevalence estimates from the BRFSS were compared to estimates from multi-source administrative claims and traditional population-based methods. Results: The estimated lifetime prevalence of self-reported MS (per 100,000 adults) was 682 (95% CI 528-836); 384 (95% CI 239-529) among males and 957 (95% CI 694-1,220) among females. Estimates were consistent across the 4 states but much higher than recently published estimates using population-based administrative claims data. This was observed for both national results and for MS prevalence estimates from other studies within specific states (MN, RI, and TX). Prevalence estimates for Caucasian, African American, and Hispanic respondents were 824, 741, and 349 per 100,000 respectively. Age and sex distributions were consistent with prior epidemiologic reports. Comorbidity and functional limitations were more pronounced among female than male respondents. Conclusions: While yielding higher overall MS prevalence estimates compared to recent studies, this large-scale self-report telephone method yielded relative prevalence estimates (e.g., prevalence patterns of MS by sex, age, and race-ethnicity) that were generally comparable to other surveillance approaches. With certain caveats, population-based telephone surveys may eventually offer the ability to investigate novel disease correlates and are relatively feasible, and affordable. Further work is needed to create a valid question set and methodology for case ascertainment before this approach could be adopted to accurately estimate MS prevalence.

Why focus on multiple sclerosis (MS) and wellness during the coronavirus disease 2019 (COVID-19) pandemic? People with MS have considerable experience coping with the uncertainty that goes along with having a highly variable, progressive disease. The COVID-19 pandemic presents new uncertainties that likely challenge the coping resources of persons with MS and cause disruptions in lifestyle habits and choices that affect wellness. Anxiety, depression, loneliness, and sedentary behavior are common in MS and now may be exacerbated by the physical distancing necessitated by the pandemic. In this context, the promotion of wellness through health behaviors has never been more important, and rehabilitation providers play a critical role in promoting wellness in the population with MS, across the life span, during this pandemic. Although derived from the MS literature, the following evidence-based physical, nutritional, and emotional wellness recommendations are relevant to not only people with MS but also to other rehabilitation populations who are adversely affected by the decreased physical and social activity, uncertainty, economic hardship, and other lifestyle restrictions common to this time. There is convincing evidence that exercise and physical activity can improve walking, balance, fatigue, depression, and quality of life in people with MS.1Motl R.W. Sandroff B.M. Kwakkel G. et al.Exercise in patients with multiple sclerosis.Lancet Neurol. 2017; 16: 848-856Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar There are also benefits in MS for cognition, anxiety, and pain.2Motl R.W. Pilutti L.A. The benefits of exercise training in multiple sclerosis.Nat Rev Neurol. 2012; 8: 487-497Crossref PubMed Scopus (311) Google Scholar,3Demaneuf T. Aitken Z. Karahalios A. et al.Effectiveness of exercise interventions for pain reduction in people with multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials.Arch Phys Med Rehabil. 2019; 100: 128-139Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Vascular comorbidities are common and have a major effect in MS,4Palladino R. Marrie R.A. Majeed A. Chataway J. Evaluating the risk of macrovascular events and mortality among people with multiple sclerosis in England.JAMA Neurol. 2020 May 4; ([Epub ahead of print])Crossref PubMed Scopus (54) Google Scholar and may even worsen the severity of COVID-19. Evidence from the general population indicates that exercise and physical activity reduce the prevalence and severity of conditions.5Lavie C.J. Ozemek C. Carbone S. Katzmarzyk P.T. Blair S.N. Sedentary behavior, exercise, and cardiovascular health.Circ Res. 2019; 124: 799-815Crossref PubMed Scopus (757) Google Scholar,6Noone C. Leahy J. Morrissey E.C. et al.Comparative efficacy of exercise and anti-hypertensive pharmacological interventions in reducing blood pressure in people with hypertension: a network meta-analysis.Eur J Prev Cardiol. 2020; 27: 247-255Crossref PubMed Scopus (39) Google Scholar These benefits may be applicable in MS,7Ranadive S.M. Yan H. Weikert M. et al.Vascular dysfunction and physical activity in multiple sclerosis.Med Sci Sports Exerc. 2012; 44: 238-243Crossref PubMed Scopus (64) Google Scholar and possibly affect disability progression in MS.8Motl R.W. Dlugonski D. Pilutti L. Sandroff B. McAuley E. Premorbid physical activity predicts disability progression in relapsing-remitting multiple sclerosis.J Neurol Sci. 2012; 323: 123-127Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar We recommend that health care providers reinforce the importance of sitting less and moving more on a daily basis by engaging in lifestyle physical activity and/or exercise amid the pandemic and after.9Kalb R. Brown T.R. Coote S. et al.Exercise and lifestyle physical activity recommendations for people with multiple sclerosis throughout the disease course.Mult Scler. 2020 Apr 23; ([Epub ahead of print])Crossref PubMed Scopus (126) Google Scholar,10Motl R.W. Lifestyle physical activity in persons with multiple sclerosis: the new kid on the MS block.Mult Scler. 2014; 20: 1025-1029Crossref PubMed Scopus (92) Google Scholar This may include simple modifications such as multiple short bouts of ambulatory and wheelchair-based physical activity in or outside the home throughout the day. Specific exercise training guidelines indicate that persons with MS should undertake 2-3 d/wk of aerobic exercise (10-30min at a moderate intensity) and 2-3 d/wk of resistance exercise (1-3 sets of between 8 and 15 repetition maximum).11Kim Y. Lai B. Mehta T. et al.Exercise training guidelines for multiple sclerosis, stroke, and Parkinson disease: rapid review and synthesis.Am J Phys Med Rehabil. 2019; 98: 613-621Crossref PubMed Scopus (111) Google Scholar Providers should highlight, with all patients, the importance of engaging in physical activity or exercise, maintaining a current routine, and consulting with professionals before making substantial or risky changes. Physical activity has many benefits, including on psychological and physical health, such that maintaining and/or increasing physical activity among people with MS could have substantial benefits during the COVID-19 pandemic. For more specific guidelines, we refer you to resources available from the National Multiple Sclerosis Society on physical activity and exercise for people living with MS. There is emerging evidence for the value of maintaining a healthy diet in both adult and pediatric MS. Higher scores on a healthy diet index (ie, higher consumption of fruits and vegetables, lower consumption of red meats and fats) have been associated with less depression, lower levels of disability, and higher patient-reported quality of life in MS.12Fitzgerald K.C. Tyry T. Salter A. et al.A survey of dietary characteristics in a large population of people with multiple sclerosis.Mult Scler Relat Disord. 2018; 22: 12-18Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar, 13Hadgkiss E.J. Jelinek G.A. Weiland T.J. Pereira N.G. Marck C.H. van der Meer D.M. The association of diet with quality of life, disability, and relapse rate in an international sample of people with multiple sclerosis.Nutr Neurosci. 2015; 18: 125-136Crossref PubMed Scopus (113) Google Scholar, 14Grotto D. Zied E. The Standard American Diet and its relationship to the health status of Americans.Nutr Clin Pract. 2010; 25: 603-612Crossref PubMed Scopus (87) Google Scholar However, 70% of Americans eat the Standard American Diet, and that includes people with MS. The Standard American Diet is a diet low in fruit and vegetable consumption and high in saturated fat, sodium, and refined sugar. Such a diet is associated with an increased risk of hypertension, cardiovascular disease, type 2 diabetes and obesity.14Grotto D. Zied E. The Standard American Diet and its relationship to the health status of Americans.Nutr Clin Pract. 2010; 25: 603-612Crossref PubMed Scopus (87) Google Scholar,15Office of Disease Prevention and Health Promotion. Current eating patterns in the United States.https://health.gov/our-work/food-nutrition/2015-2020-dietary-guidelines/guidelines/chapter-2/current-eating-patterns-in-the-united-states/Date accessed: May 8, 2020Google Scholar Obesity, diabetes, and severe cardiovascular disease have been identified as risk factors for serious illness from COVID-19.16Centers for Disease Control and Prevention. Coronavirus disease 2019 (COVID-19).https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/groups-at-higher-risk.htmlDate accessed: May 8, 2020Google Scholar In MS, lower levels of vascular comorbidities that include cardiovascular disease, diabetes, hypertension, hypercholesterolemia, and peripheral vascular disease have been shown to extend the ability to walk without assistance by approximately 6 years.17Marrie R.A. Rudick R. Horwitz R. et al.Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis.Neurology. 2010; 74: 1041-1047Crossref PubMed Scopus (343) Google Scholar We recommend that providers keep in mind that there is not sufficient scientific evidence for recommending a specific diet in MS. What providers can do is encourage their patients with MS to maintain simple healthy diet habits that include: (1) make at least half your plate at meals fruits and vegetables (excluding starchy vegetables); (2) choose healthy fats that include olive oil and grapeseed oil as well as fish and poultry that are lower in saturated fat; (3) add whole foods; and (4) read food labels; any food that has less than 5 ingredients is less likely to have excess sodium and refined sugar. Key advice during this COVID-19 pandemic is to start with a small change rather than a diet overhaul by phasing in healthy foods and healthy eating habits while reducing the less healthy ones. We recommend that providers remind their patients that diet is important in MS because it affects MS disability, emotional wellness, and quality of life. For many, the COVID-19 pandemic has been a time of uncertainty and powerlessness; having control over diet is empowering and offers the opportunity for experimenting with home meal preparation and increased time for family meal sharing and conversation. Emotional wellness plays an influential role in the overall health of people living with MS and other chronic conditions. Depressive disorders, affecting 1 in 3 people with MS,18Boeschoten R.E. Braamse A.M.J. Beekman A.T.F. et al.Prevalence of depression and anxiety in multiple sclerosis: a systematic review and meta-analysis.J Neurol Sci. 2017; 372: 331-341Abstract Full Text Full Text PDF PubMed Scopus (393) Google Scholar have adverse effects on cognition, pain, fatigue, adherence to exercise and disease modifying therapies, and overall quality of life.19Fernández-Jiménez E. Arnett P.A. Impact of neurological impairment, depression, cognitive function and coping on quality of life of people with multiple sclerosis: a relative importance analysis.Mult Scler. 2015; 21: 1468-1472Crossref PubMed Scopus (34) Google Scholar, 20Marrie R.A. Hanwell H. General health issues in multiple sclerosis: comorbidities, secondary conditions, and health behaviors.Continuum (Minneap Minn). 2013; 19: 1046-1057PubMed Google Scholar, 21Turner A.P. Alschuler K.N. Hughes A.J. et al.Mental health comorbidity in MS: depression, anxiety, and bipolar disorder.Curr Neurol Neurosci Rep. 2016; 16: 106Crossref PubMed Scopus (33) Google Scholar Anxiety disorders are also more prevalent and associated with a range of negative effects on health and well-being.21Turner A.P. Alschuler K.N. Hughes A.J. et al.Mental health comorbidity in MS: depression, anxiety, and bipolar disorder.Curr Neurol Neurosci Rep. 2016; 16: 106Crossref PubMed Scopus (33) Google Scholar Conversely, resilience, the ability to regain or maintain well-being despite experiencing adversity or chronic stressors, is common among people with MS22Amtmann D. Bamer A.M. Alschuler K.N. et al.Development of a resilience item bank and short forms.Rehabil Psychol. 2020; 65: 145-157Crossref PubMed Scopus (16) Google Scholar and positively affects MS symptoms, function, and quality of life.23Edwards K.A. Alschuler K.A. Ehde D.M. Battalio S.L. Jensen M.P. Changes in resilience predict function in adults with physical disabilities: a longitudinal study.Arch Phys Med Rehabil. 2017; 98: 329-336Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar, 24Koelmel E. Hughes A.J. Alschuler K.N. Ehde D.M. Resilience mediates the longitudinal relationships between social support and mental health outcomes in multiple sclerosis.Arch Phys Med Rehabil. 2017; 98: 1139-1148Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar, 25Silverman A.M. Molton I.R. Alschuler K.N. Ehde D.M. Jensen M.P. Resilience predicts functional outcomes in people aging with disability: a longitudinal investigation.Arch Phys Med Rehabil. 2015; 96: 1262-1268Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar Fortunately, robust evidence indicates that psychological interventions, including cognitive behavioral therapy, mindfulness-based interventions, stress management, self-hypnosis training, and/or self-management skills training, improve depression,26Fiest K.M. Walker J.R. Bernstein C.N. et al.Systematic review and meta-analysis of interventions for depression and anxiety in persons with multiple sclerosis.Mult Scler Relat Disord. 2016; 5: 12-26Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar,27Minden S.L. Feinstein A. Kalb R.C. et al.Evidence-based guideline: assessment and management of psychiatric disorders in individuals with MS: report of the Guideline Development Subcommittee of the American Academy of Neurology.Neurology. 2014; 82: 174-181Crossref PubMed Scopus (172) Google Scholar stress,28Taylor P. Dorstyn D.S. Prior E. Stress management interventions for multiple sclerosis: a meta-analysis of randomized controlled trials.J Health Psychol. 2020; 25: 266-279Crossref PubMed Scopus (13) Google Scholar fatigue,29Phyo A.Z.Z. Demaneuf T. De Livera A.M. et al.The efficacy of psychological interventions for managing fatigue in people with multiple sclerosis: a systematic review and meta-analysis.Front Neurol. 2018; 9: 149Crossref PubMed Scopus (25) Google Scholar pain,30Turner A.P. Knowles L.M. Behavioral interventions in multiple sclerosis.Fed Pract. 2020; 37 (S31-S35)PubMed Google Scholar, 31Ehde D.M. Elzea J.L. Verrall A.M. Gibbons L.E. Smith A.E. Amtmann D. Efficacy of a telephone-delivered self-management intervention for persons with multiple sclerosis: a randomized controlled trial with a one-year follow-up.Arch Phys Med Rehabil. 2015; 96: 1945-1958Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar, 32Simpson R. Booth J. Lawrence M. Byrne S. Mair F. Mercer S. Mindfulness based interventions in multiple sclerosis--a systematic review.BMC Neurol. 2014; 14: 15Crossref PubMed Scopus (125) Google Scholar and sleep.30Turner A.P. Knowles L.M. Behavioral interventions in multiple sclerosis.Fed Pract. 2020; 37 (S31-S35)PubMed Google Scholar,33Cavalera C. Rovaris M. Mendozzi L. et al.Online meditation training for people with multiple sclerosis: a randomized controlled trial.Mult Scler. 2019; 25: 610-617Crossref PubMed Scopus (49) Google Scholar Many of these interventions can successfully treat multiple symptoms, such as mood, pain, and fatigue, at once,31Ehde D.M. Elzea J.L. Verrall A.M. Gibbons L.E. Smith A.E. Amtmann D. Efficacy of a telephone-delivered self-management intervention for persons with multiple sclerosis: a randomized controlled trial with a one-year follow-up.Arch Phys Med Rehabil. 2015; 96: 1945-1958Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar making multisymptom management feasible. We recommend that providers assess and address patients' emotional wellness as part of standard care, both during the COVID-19 crisis and after it has passed. Because screening alone is rarely sufficient to address emotional wellness,27Minden S.L. Feinstein A. Kalb R.C. et al.Evidence-based guideline: assessment and management of psychiatric disorders in individuals with MS: report of the Guideline Development Subcommittee of the American Academy of Neurology.Neurology. 2014; 82: 174-181Crossref PubMed Scopus (172) Google Scholar providers should collaborate with patients to generate a comprehensive plan for addressing psychosocial distress, symptom management, and adherence to other lifestyle recommendations. The rapid transition to and coverage for telehealth psychological services (both video and telephone) during the pandemic provides an opportunity for patients with MS to access psychological services from their homes. Telehealth is an effective mode of care for patients with MS,30Turner A.P. Knowles L.M. Behavioral interventions in multiple sclerosis.Fed Pract. 2020; 37 (S31-S35)PubMed Google Scholar and those with varying severity and symptoms can benefit from such care, including those with cognitive dysfunction.34Ehde D.M. Arewasikporn A. Alschuler K.N. Hughes A.J. Turner A.P. Moderators of treatment outcomes after telehealth self-management and education in adults with multiple sclerosis: a secondary analysis of a randomized controlled trial.Arch Phys Med Rehabil. 2018; 99: 1265-1272Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar If telehealth psychological care with a professional is not needed, preferred, or available, a range of empirically-informed online and self-help strategies are available. For example, My MS Toolkit (https://mymstoolkit.com) is a free, online self-management program based on an efficacious telehealth self-management intervention.31Ehde D.M. Elzea J.L. Verrall A.M. Gibbons L.E. Smith A.E. Amtmann D. Efficacy of a telephone-delivered self-management intervention for persons with multiple sclerosis: a randomized controlled trial with a one-year follow-up.Arch Phys Med Rehabil. 2015; 96: 1945-1958Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar Fortunately, the very behaviors and skills that can be used to improve emotional well-being in MS are skills that can help people cope with the anxiety, increased isolation, and uncertainty that many are experiencing during the COVID-19 pandemic. There is good evidence that health behaviors can improve and sustain many components of wellness in MS. Rehabilitation providers can be powerful advocates of the benefits of physical activity, diet, and emotional wellness for MS symptom management, quality of life, and the reduction of comorbid conditions that affect both MS disability and risk of COVID-19 illness severity. We strongly urge health care providers to share information on wellness with their patients who have MS and other chronic conditions, encouraging adoption of such behaviors. There is a pressing need for a collaborative approach for managing each person's health amid the economic and social limitations attendant to COVID-19. Fallout from these limitations will be widespread and affect health in many ways both in the short and long term. Providers are urged to collaborate with the National Multiple Sclerosis Society and other advocacy organizations to disseminate wellness materials and resources (listed below) while providing guidance tailored to each patient's needs, abilities, means and preferences. Supplemental material and resources: https://www.nationalmssociety.org/Living-Well-With-MS/Diet-Exercise-Healthy-Behaviors https://www.nationalmssociety.org/Living-Well-With-MS/Emotional-Well-Being https://www.nationalmssociety.org/Resources-Support/Library-Education-Programs/Brochures/Staying-Well https://www.nationalmssociety.org/Programs-and-Services/Resources/Wellness-Discussion-Guide-for-People-with-MS-and-T?page=1&orderby=3&order=asc For information specific to COVID-19 and wellness, see https://www.nationalmssociety.org/coronavirus-covid-19-information American Heart Association website recipes, helpful videos, kitchen skills, and techniques: https://recipes.heart.org/en Can Do MS website with programs and services: https://www.cando-ms.org

There is a growing need for patient and public involvement (PPI) to inform the way that research is developed and performed. International randomized controlled trials are particularly likely to benefit from PPI, but guidance is lacking on how or when it should be incorporated. In this article, we describe the PPI process that occurred during the design and initiation of an international treatment clinical trial in MS. PPI was incorporated using a structured approach, aiming to minimize bias and achieve equivalence in study design, implementation, and interpretation. Methods included PPI representation within the study research team, and the use of focus groups, analyzed using thematic framework analysis. We report the outcomes of PPI and make recommendations on its use in other neurology clinical trials. By sharing our model for PPI, we aim to maximize effectiveness of future public involvement and to allow its effect to be better evaluated.

Disease course in people with multiple sclerosis (MS) is heterogeneous. The impact of dietary and nutritional factors on MS prognosis is of interest to both patients and clinicians; differences in diet are hypothesized to contribute to disease evolution over time. However, studying diet, especially in people with MS, introduces methodologic complexity that should be recognized. In this review, we focus on methodological aspects relevant to the conduct of dietary interventions in people with MS, given our experience in leading such studies and the challenges we encountered in the realization of this work. We summarize key aspects of study design and important considerations, regardless of the specifics of the actual study (e.g. the particular diet of interest, target MS population, etc.). We discuss strategies for the design of the intervention as well as the selection of appropriate study endpoints. Finally, we provide an overview of strategies to improve the rigor of conducting dietary studies in people with MS.

Objective: To compare characteristics of secondary-progressive (SPMS) vs. relapsing-remitting (RRMS) patients. Background: The clinical course of patients with different MS subtypes is varied. The Corrona MS Registry in collaboration with National Multiple Sclerosis Society studies real-world burden of disease and safety/effectiveness of MS disease modifying therapies (DMTs). Design/Methods: Corrona MS is a US multicenter, observational registry. Means and proportions of enrollment visit characteristics were compared between SPMS vs. RRMS using pair-wise statistical comparisons. Results: As of 1/22/19, 557 RRMS and 80 SPMS patients were enrolled. SPMS vs. RRMS patients were older (57.0, 48.6 years, p Conclusions: SPMS and RRMS patients in Corrona MS demonstrate important differences in age, disease duration, functional system involvement, disease measures, employment status and patient/clinician DMT response impression. Corrona MS can explore phenotypic differences between subtypes, such as active vs. non-active SPMS. Disclosure: Dr. Kantor has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting fees and/or fees for non-CME services (AbbVie, Actelion, Bayer, Biogen, Celgene, Corrona, EMD Serono, Genentech, Mylan, Novartis, and Sanofi).. Dr. Kantor has received research support from Research grants (Actelion).. Dr. Bebo has nothing to disclose. Yes; Accordant, Alexion, Bayer, Biogen MA, Inc., Celgene Corporation, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, Novartis Pharmaceuticals Corporation, Serono, TG Therapeutics Yes; Actelion, Alkermes, Corrona LLD, Genentech/Roche, MedDay, NINDS, Novartis Pharmaceuticals Corporation, PCORIReceived consulting fees, speaker’s bureau and advisory work from Biogen, Celgene, Chugai, EMD Serono, Genetech/Roche, MedDay, Novartis, Sanofi, Genzyme, Teva, and TG Therapeutics Received contracted research from Biogen, Celgene, Chugai, EMD Serono, Genetech/Roche, MedDay, Novartis, Sanofi, Genzyme, Teva, and TG Therapeutics.Dr. Bermel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Genzyme, Genentech, Novartis. Dr. Bermel has received royalty, license fees, or contractual rights payments from intellectual property underlying the Multiple Sclerosis Performance Test, currently licensed to Qr8 Health and Biogen. Dr. Bermel has received research support from Biogen, Genentech, and Novartis. Dr. Greenberg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Corrona LLC.Dr. Malley has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Corrona, LLC.. Dr. McLean has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Corrona, LLC. Dr. Rebello has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Corrona, LLC. Dr. LaRocca has nothing to disclose. Dr. Miller has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Accordant Health Services (Caremark), Adamas, BiogenIdec, Celgene, Corrona, EMD Serono, Genzyme/Sanofi, Mallinckrodt, Mapi-Pharma, Novartis, and Roche/Genentech. Dr. Miller has received research support from BiogenIdec, Mallinckrodt (Questcor), Novartis, Roche/Genentech, and MedDay.

BACKGROUND: Multiple sclerosis (MS) is among the most prevalent chronic neurological conditions worldwide and is associated with a wide range of symptoms and psychosocial impacts. Quality of life (QOL) is recognized as a comprehensive and person-centered framework for exploring and understanding these impacts. Although there is a strong history of including people with MS in the development of health-related and patient-reported outcomes QOL instruments in MS, there have been relatively few large-scale qualitative investigations of what is important to the QOL of people with MS. As part of an ongoing evaluation by the National Multiple Sclerosis Society (NMSS), in which the NMSS is seeking to evaluate the impact of its work on the lives of people living with MS, we surveyed a sample of 748 Americans with MS about the areas of their life that are most important to their QOL. RESULTS: The results suggest that social relationships, health, independence, and participation in meaningful activities, including employment, were among their top priorities. The diversity of life areas identified underscores the importance of understanding the individual's unique priorities and experiences of QOL, and recognizing the diversity of the population. CONCLUSION: The results are discussed in terms of the implications for understanding of priorities and experiences of Americans living with MS.

Background: The proliferation of computerized neuropsychological assessment devices (CNADs) for screening and monitoring cognitive impairment is increasing exponentially. Previous reviews of computerized tests for multiple sclerosis (MS) were primarily qualitative and did not rigorously compare CNADs on psychometric properties. Objective: We aimed to systematically review the literature on the use of CNADs in MS and identify test batteries and single tests with good evidence for reliability and validity. Method: A search of four major online databases was conducted for publications related to computerized testing and MS. Test–retest reliability and validity coefficients and effect sizes were recorded for each CNAD test, along with administration characteristics. Results: We identified 11 batteries and 33 individual tests from 120 peer-reviewed articles meeting the inclusion criteria. CNADs with the strongest psychometric support include the CogState Brief Battery, Cognitive Drug Research Battery, NeuroTrax, CNS-Vital Signs, and computer-based administrations of the Symbol Digit Modalities Test. Conclusion: We identified several CNADs that are valid to screen for MS-related cognitive impairment, or to supplement full, conventional neuropsychological assessment. The necessity of testing with a technician, and in a controlled clinic/laboratory environment, remains uncertain.

Objective To generate a national multiple sclerosis (MS) prevalence estimate for the United States by applying a validated algorithm to multiple administrative health claims (AHC) datasets. Methods A validated algorithm was applied to private, military, and public AHC datasets to identify adult cases of MS between 2008 and 2010. In each dataset, we determined the 3-year cumulative prevalence overall and stratified by age, sex, and census region. We applied insurance-specific and stratum-specific estimates to the 2010 US Census data and pooled the findings to calculate the 2010 prevalence of MS in the United States cumulated over 3 years. We also estimated the 2010 prevalence cumulated over 10 years using 2 models and extrapolated our estimate to 2017. Results The estimated 2010 prevalence of MS in the US adult population cumulated over 10 years was 309.2 per 100,000 (95% confidence interval [CI] 308.1–310.1), representing 727,344 cases. During the same time period, the MS prevalence was 450.1 per 100,000 (95% CI 448.1–451.6) for women and 159.7 (95% CI 158.7–160.6) for men (female:male ratio 2.8). The estimated 2010 prevalence of MS was highest in the 55- to 64-year age group. A US north-south decreasing prevalence gradient was identified. The estimated MS prevalence is also presented for 2017. Conclusion The estimated US national MS prevalence for 2010 is the highest reported to date and provides evidence that the north-south gradient persists. Our rigorous algorithm-based approach to estimating prevalence is efficient and has the potential to be used for other chronic neurologic conditions.

Objective Considerable gaps exist in knowledge regarding the prevalence of neurologic diseases, such as multiple sclerosis (MS), in the United States. Therefore, the MS Prevalence Working Group sought to review and evaluate alternative methods for obtaining a scientifically valid estimate of national MS prevalence in the current health care era. Methods We carried out a strengths, weaknesses, opportunities, and threats (SWOT) analysis for 3 approaches to estimate MS prevalence: population-based MS registries, national probability health surveys, and analysis of administrative health claims databases. We reviewed MS prevalence studies conducted in the United States and critically examined possible methods for estimating national MS prevalence. Results We developed a new 4-step approach for estimating MS prevalence in the United States. First, identify administrative health claim databases covering publicly and privately insured populations in the United States. Second, develop and validate a highly accurate MS case-finding algorithm that can be standardly applied in all databases. Third, apply a case definition algorithm to estimate MS prevalence in each population. Fourth, combine MS prevalence estimates into a single estimate of US prevalence, weighted according to the number of insured persons in each health insurance segment. Conclusions By addressing methodologic challenges and proposing a new approach for measuring the prevalence of MS in the United States, we hope that our work will benefit scientists who study neurologic and other chronic conditions for which national prevalence estimates do not exist.

Objective To develop a valid algorithm for identifying multiple sclerosis (MS) cases in administrative health claims (AHC) datasets. Methods We used 4 AHC datasets from the Veterans Administration (VA), Kaiser Permanente Southern California (KPSC), Manitoba (Canada), and Saskatchewan (Canada). In the VA, KPSC, and Manitoba, we tested the performance of candidate algorithms based on inpatient, outpatient, and disease-modifying therapy (DMT) claims compared to medical records review using sensitivity, specificity, positive and negative predictive values, and interrater reliability (Youden J statistic) both overall and stratified by sex and age. In Saskatchewan, we tested the algorithms in a cohort randomly selected from the general population. Results The preferred algorithm required ≥3 MS-related claims from any combination of inpatient, outpatient, or DMT claims within a 1-year time period; a 2-year time period provided little gain in performance. Algorithms including DMT claims performed better than those that did not. Sensitivity (86.6%–96.0%), specificity (66.7%–99.0%), positive predictive value (95.4%–99.0%), and interrater reliability (Youden J = 0.60–0.92) were generally stable across datasets and across strata. Some variation in performance in the stratified analyses was observed but largely reflected changes in the composition of the strata. In Saskatchewan, the preferred algorithm had a sensitivity of 96%, specificity of 99%, positive predictive value of 99%, and negative predictive value of 96%. Conclusions The performance of each algorithm was remarkably consistent across datasets. The preferred algorithm required ≥3 MS-related claims from any combination of inpatient, outpatient, or DMT use within 1 year. We recommend this algorithm as the standard AHC case definition for MS.

Objective To generate a national multiple sclerosis (MS) prevalence estimate for the United States by applying a validated algorithm to multiple administrative health claims (AHC) datasets. Methods A validated algorithm was applied to private, military, and public AHC datasets to identify adult cases of MS between 2008 and 2010. In each dataset, we determined the 3-year cumulative prevalence overall and stratified by age, sex, and census region. We applied insurance-specific and stratum-specific estimates to the 2010 US Census data and pooled the findings to calculate the 2010 prevalence of MS in the United States cumulated over 3 years. We also estimated the 2010 prevalence cumulated over 10 years using 2 models and extrapolated our estimate to 2017. Results The estimated 2010 prevalence of MS in the US adult population cumulated over 10 years was 309.2 per 100,000 (95% confidence interval [CI] 308.1-310.1), representing 727,344 cases. During the same time period, the MS prevalence was 450.1 per 100,000 (95% CI 448.1-451.6) for women and 159.7 (95% CI 158.7-160.6) for men (female:male ratio 2.8). The estimated 2010 prevalence of MS was highest in the 55- to 64-year age group. A US north-south decreasing prevalence gradient was identified. The estimated MS prevalence is also presented for 2017. Conclusion The estimated US national MS prevalence for 2010 is the highest reported to date and provides evidence that the north-south gradient persists. Our rigorous algorithm-based approach to estimating prevalence is efficient and has the potential to be used for other chronic neurologic conditions.

BACKGROUND:Anecdotal reports suggest shortages among neurologists who provide multiple sclerosis (MS) patient care. However, little information is available regarding the current and future supply of and demand for this neurologist workforce.METHODS:We used information from neurologist and neurology resident surveys, professional organizations, and previously reported studies to develop a model assessing the projected supply and demand (ie, expected physician visits) of neurologists providing MS patient care. Model projections extended through 2035.RESULTS:The capacity for MS patient visits among the overall neurologist workforce is projected to increase by approximately 1% by 2025 and by 12% by 2035. However, the number of individuals with MS may increase at a greater rate, potentially resulting in decreased access to timely and high-quality care for this patient population. Shortages in the MS neurologist workforce may be particularly acute in small cities and rural areas. Based on model sensitivity analyses, potential strategies to substantially increase the capacity for MS physicians include increasing the number of patients with MS seen per neurologist, offering incentives to decrease neurologist retirement rates, and increasing the number of MS fellowship program positions.CONCLUSIONS:The neurologist workforce may be adequate for providing MS care currently, but shortages are projected over the next 2 decades. To help ensure access to needed care and support optimal outcomes among individuals with MS, policies and strategies to enhance the MS neurologist workforce must be explored now.

Background: The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability. Objectives: (1) To assess the current literature and available data on functional performance outcome measures (PerfOs) and (2) to determine suitability of using PerfOs to quantify MS disability in MS clinical trials. Methods: (1) Identify disability dimensions common in MS; (2) conduct a comprehensive literature review of measures for those dimensions; (3) develop an MS Clinical Data Interchange Standards Consortium (CDISC) data standard; (4) create a database of standardized, pooled clinical trial data; (5) analyze the pooled data to assess psychometric properties of candidate measures; and (6) work with regulatory agencies to use the measures as primary or secondary outcomes in MS clinical trials. Conclusion: Considerable data exist supporting measures of the functional domains ambulation, manual dexterity, vision, and cognition. A CDISC standard for MS ( http://www.cdisc.org/therapeutic#MS ) was published, allowing pooling of clinical trial data. MSOAC member organizations contributed clinical data from 16 trials, including 14,370 subjects. Data from placebo-arm subjects are available to qualified researchers. This integrated, standardized dataset is being analyzed to support qualification of disability endpoints by regulatory agencies.