Risk Factors for Chronic Prescription Opioid Use in Multiple Sclerosis.

OBJECTIVE: To characterize patterns of prescription opioid use among individuals with multiple sclerosis (MS) and identify risk factors associated with chronic use. DESIGN: Retrospective longitudinal cohort study examining US Department of Veterans Affairs electronic medical record data of Veterans with MS. The annual prevalence of prescription opioid use by type (any, acute, chronic, incident chronic) was calculated for each study year (2015-2017). Multivariable logistic regression was used to identify demographics and medical, mental health, and substance use comorbidities in 2015-2016 associated with chronic prescription opioid use in 2017. SETTING: US Department of Veterans Affairs, Veteran's Health Administration. PARTICIPANTS: National sample of Veterans with MS (N=14,974). MAIN OUTCOME MEASURE: Chronic prescription opioid use (≥90 days). RESULTS: All types of prescription opioid use declined across the 3 study years (chronic opioid use prevalence=14.6%, 14.0%, and 12.2%, respectively). In multivariable logistic regression, prior chronic opioid use, history of pain condition, paraplegia or hemiplegia, post-traumatic stress disorder, and rural residence were associated with greater risk of chronic prescription opioid use. History of dementia and psychotic disorder were both associated with lower risk of chronic prescription opioid use. CONCLUSION: Despite reductions over time, chronic prescription opioid use remains common among a substantial minority of Veterans with MS and is associated with multiple biopsychosocial factors that are important for understanding risk for long-term use.

Demographic and Clinical Factors Are Associated With Frequent Short-Notice Cancellations in Veterans With Multiple Sclerosis on Disease Modifying Therapies.

OBJECTIVES: (1) To identify the rate of short-notice canceled appointments in a large national sample of persons with multiple sclerosis (MS) and (2) examine the demographic and clinical factors associated with frequent cancellations. DESIGN: Retrospective cross-sectional cohort using electronic health records. SETTING: Veterans Health Administration. PARTICIPANTS: Veterans with MS (N=3742) who were part of the Veterans Health Administraiton's MS Center of Excellence Data Repository and (1) had at least one outpatient appointment at the VA in 2013, (2) were alive in 2015, and (3) were prescribed a disease modifying therapy (DMT). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Frequent short-notice cancellations, defined as >20% of scheduled appointments canceled with less than 24-hour notification over a 24-month period. This threshold was based on the definition of ≤80% for suboptimal treatment adherence. Several demographics and clinical variables were examined as potential explanatory factors. RESULTS: Approximately 75% (n=2827) had at least 1 short-notice cancellation, with more than 3% (n=117) categorized as frequent cancelers. The odds of frequent cancellations were greater in women (odds ratio [OR], 1.81; P=.004) and among 18- to 44-year-olds (OR, 2.77; P=.004) and 45- to 64-year-olds (OR, 2.49; P=.003) compared to those over 65. The odds were lower among persons who lived <25 miles away (OR, 0.58; P=.043) compared with persons who lived ≥75 miles away and those who had at least 1 emergency department visit (OR, 0.55; P=.012). CONCLUSIONS: Short-notice cancellations are common in persons with MS, although few have more than 20%. These findings highlight who is at greater risk for frequent cancellation and disruptions in their care. Although additional research is needed, the results provide insights into how clinics may approach handling frequent short-notice cancellations among persons with MS.

Risk Factors for Suboptimal Medication Adherence in Persons With Multiple Sclerosis: Development of an Electronic Health Record-Based Explanatory Model for Disease-Modifying Therapy Use.

OBJECTIVE: To determine which factors are associated with suboptimal disease-modifying therapy (DMT) adherence and to develop an explanatory model that could be used to identify individuals at risk and potentially inform interventions. DESIGN: Cross-sectional cohort study using electronic health records. SETTING: Veterans Health Administration (VA). PARTICIPANTS: Veterans with multiple sclerosis (MS) (N=2939; 79.69% men) who received care through the VA and were included in the VA MS Center of Excellence Data Repository. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Suboptimal DMT adherence (<80%), demographics, co-occurring conditions, and health care use. RESULTS: Nearly 31% of participants had suboptimal adherence. Flags for suboptimal adherence included >20% missed appointments (odds ratio [OR], 3.78; 95% CI, 2.45-2.82), traumatic brain injuries (OR, 1.55; 95% CI, 1.12-2.14), age younger than 59 years (OR, 1.47; 95% CI, 1.23-1.74), ≥1 emergency department visits (OR, 1.40; 95% CI, 1.18-1.67), mood disorders (ie, depressive and bipolar disorders) (OR, 1.40; 95% CI, 1.18-1.66), and service connection (OR, 1.22; 95% CI, 1.01-1.47). Hyperlipidemia (OR, 0.77; 95% CI, 0.65-0.92) and being issued a wheelchair (OR, 0.83; 95% CI, 0.70-1.00) were associated with lower risk. CONCLUSIONS: Suboptimal adherence to DMTs continues to be an issue. Interventions that focus on person-level barriers should be urgently explored to increase adherence and improve self-management abilities.

Risk Factors for Suicide in a National Sample of Veterans With Multiple Sclerosis.

OBJECTIVES: To examine risk factors in the year before suicide in a national sample of United States veterans with multiple sclerosis (MS), as well as means of suicide and receipt of mental health services prior to death. DESIGN: Case control study. Individuals in the Veterans Affairs MS National Data Repository were linked to the National Death Index Plus to obtain death records, including specific causes of death. Participants were veterans with MS who died by suicide and randomly selected nonsuicide MS controls (5 per participant) who were alive at the time of the index suicide. Mental health disorders and medical comorbidities were identified in the year before death for suicides and during the identical time period for controls. SETTING: Veterans Health Administration. PARTICIPANTS: Veterans (N=426) who received treatment for MS in the United States Veterans Health Administration between 1999 and 2011. There were 71 deaths by suicide and 355 randomly selected controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Suicide. RESULTS: Results from the adjusted multivariable model suggest that the following factors were associated with an increased risk for suicide: male sex (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.35-9.42), depression (OR, 1.82; 95% CI, 1.03-3.23), and alcohol use disorder (OR, 3.10; 95% CI, 1.38-6.96). Half (50.7%) had a mental health appointment in the year before suicide. The primary means of suicide was by firearm (62.0%). CONCLUSIONS: Routine assessment of suicide risk in individuals with MS is warranted, particularly for those with recent history of depression or alcohol use disorder.

Sleep and its associations with perceived and objective cognitive impairment in individuals with multiple sclerosis.

Problems with sleep and cognitive impairment are common among people with multiple sclerosis (MS). The present study examined the relationship between self-reported sleep and both objective and perceived cognitive impairment in MS. Data were obtained from the baseline assessment of a multi-centre intervention trial (NCT00841321). Participants were 121 individuals with MS. Nearly half (49%) of participants met the criteria for objective cognitive impairment; however, cognitively impaired and unimpaired participants did not differ on any self-reported sleep measures. Nearly two-thirds (65%) of participants met the criteria for 'poor' sleep, and poorer sleep was significantly associated with greater levels of perceived cognitive impairment. Moreover, the relationships between self-reported sleep and perceived cognitive impairment were significant beyond the influence of clinical and demographic factors known to influence sleep and cognitive functioning (e.g. age, sex, education level, disability severity, type of MS, disease duration, depression and fatigue). However, self-reported sleep was not associated with any measures of objective cognitive impairment. Among different types of perceived cognitive impairment, poor self-reported sleep was most commonly related to worse perceived executive function (e.g. planning/organization) and prospective memory. Results from the present study emphasize that self-reported sleep is significantly and independently related to perceived cognitive impairment in MS. In terms of clinical implications, interventions focused on improving sleep may help improve perceived cognitive function and quality of life in this population; however, the impact of improved sleep on objective cognitive function requires further investigation.

Mental Health Comorbidity in MS: Depression, Anxiety, and Bipolar Disorder.

Among individuals with multiple sclerosis (MS), mental health comorbidities play a significant role in contributing to secondary disability and detracting from quality of life. This review examines current evidence surrounding three mental health issues of particular relevance to MS: depression, anxiety, and bipolar disorder. We review what is known of the prevalence, correlates, screening mechanisms, and current treatment of each issue and provide recommendations for future areas of research.

Smoking and physical activity: examining health behaviors and 15-year mortality among individuals with multiple sclerosis.

OBJECTIVES: To examine 2 modifiable health behaviors-smoking and physical activity-and their relationship to mortality among individuals with multiple sclerosis (MS). DESIGN: Secondary analysis of Large Health Survey. SETTING: Data were obtained from a linkage of the Veterans Affairs (VA) MS National Data Repository, containing information on service provision to all individuals with MS receiving health services within the U.S. Department of Veterans Affairs; the VA 1999 Large Health Survey, containing information on smoking and physical activity; and the VA Vital Status File. All-cause mortality was examined for the 15-year period from 1999 through 2013. PARTICIPANTS: Participants (N=2994) with MS who completed the Large Health Survey containing information on smoking and physical activity. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Survival. RESULTS: There were 1500 deaths (50.1%) during the study period. Cox proportional hazard analyses were conducted to examine the association between smoking and physical activity and 15-year mortality. After adjusting for demographic factors, physical functioning, mental health, and comorbid medical conditions, baseline smoking was associated with greater mortality (hazard ratio [HR]=1.38; 95% confidence interval [CI], 1.184-1.60). Higher levels of baseline physical activity were associated with lower mortality (activity 1-2 times/wk: HR=.64; 95% CI, .518-.798; activity ≥3 times/wk: HR=.53; 95% CI, .388-.715). CONCLUSIONS: Results suggest that modifiable health behaviors represent a promising opportunity for intervention to improve the lives of individuals with MS.

Cognitive Impairment and Community Integration Outcomes in Individuals Living With Multiple Sclerosis.

OBJECTIVES: To determine the association between unique domains of cognitive impairment and community integration in individuals with multiple sclerosis (MS), and to determine the contributions of cognitive impairment to community integration beyond the influence of demographic and clinical variables. DESIGN: Cross-sectional analysis of objective neuropsychological assessment and self-report data. Data were collected during baseline assessment of a randomized, multisite controlled trial of ginkgo biloba for cognitive impairment in MS. Hierarchical regression analyses examined the association between subjective and objective measures of cognitive impairment and 3 domains of community integration, adjusting for relevant covariates. SETTING: Two Veterans Affairs medical center MS clinics. PARTICIPANTS: Adults (N=121; ages 24-65y) with a confirmed MS diagnosis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Primary outcomes were scores on the Home Integration (CIQ-H), Social Integration (CIQ-S), and Productivity (CIQ-P) domains of the Community Integration Questionnaire (CIQ). RESULTS: Cognitive impairment was associated with lower scores on the CIQ-H and CIQ-S, but not the CIQ-P. Greater levels of subjective cognitive impairment were associated with lower scores on the CIQ-H and CIQ-S. Greater levels of objective cognitive impairment, specifically slower processing speed and poorer inhibitory control, were related to lower CIQ-S scores. Subjective and objective measures of cognitive impairment were significantly and independently associated with CIQ-S. CONCLUSIONS: Objective cognitive impairment may interfere with participation in social activities. Subjective cognitive impairment is also important to assess, because individuals who perceive themselves to be cognitively impaired may be less likely to participate in both home and social activities. Clinical interventions to enhance community integration in individuals with MS may benefit from addressing objective and subjective cognitive impairment by integrating cognitive rehabilitation approaches with self-efficacy-enhancing strategies.

Multiple sclerosis in gulf war era veterans. 2. Military deployment and risk of multiple sclerosis in the first gulf war.

BACKGROUND: Concern has been raised that US veterans of the 1990-1991 Gulf War (GW1) may be at increased risk to develop neurologic disease. METHODS: An incident cohort of multiple sclerosis (MS) and other demyelinating disease (ODD) was assembled from the US military comprising the Gulf War era (1990-2007). Cases of MS and ODD meeting standard diagnostic criteria were matched to a database of all active duty personnel from the Department of Defense. Relative risk (RR) estimates for MS and all demyelinating disease based on onset, deployment status, and exposures were calculated. RESULTS: For GW1, a total of 1,841 incident cases of definite MS and ODD were identified, with 387 among 696,118 deployed and 1,454 among 1,786,215 nondeployed personnel. The RR for MS alone among those deployed compared to those nondeployed was 0.69 (confidence interval, CI: 0.61-0.78), with 0.72 (CI: 0.62-0.83) in men and 0.96 (CI: 0.75-1.22) in women. Deployment was also nonsignificant or protective as an MS risk factor across racial groups, all age groups, and each military service. RRs for MS by service were: Air Force 0.71 (CI: 0.53-0.96), Army 0.80 (CI: 0.67-0.96), Marines 0.96 (CI: 0.63-1.47), and Navy 0.56 (CI: 0.43-0.74). CONCLUSION: Military deployment to GW1 was not a risk factor for developing MS.

Improving prospective memory in persons with multiple sclerosis via telehealth: A randomized feasibility study.

BACKGROUND: Persons with multiple sclerosis (PwMS) can experience deficits in prospective memory (PM) or "remembering to remember," which are associated with functional difficulties. However, no cognitive rehabilitation intervention has specifically addressed improving PM in PwMS. The Telehealth PM Intervention (TPMI) provides a novel combination of two strategies-visual imagery and implementation intentions-that have each been beneficial in other populations. This study aimed to evaluate the feasibility of TPMI and its preliminary efficacy, which could be used to inform future trials. METHODS: Participants (n = 35) were PwMS who were pre-screened and endorsed experiencing problems "remembering places they have to be" and "things they have to do." After completing a baseline evaluation, which included objective (Memory for Intentions Test; MIST) and subjective (Perceived Deficits Questionnaire; PDQ-PM) measures of PM, participants were randomized to either the active treatment (TPMI; n = 17) or active control group (Control; n = 18). TPMI was offered through remote one-on-one sessions twice a week over a four-week period. Participants were asked about treatment credibility and expectancy during the first session. The MIST and PDQ-PM were repeated at post-treatment, where treatment satisfaction was also captured. Mann-Whitney U and chi-square tests were used to examine the feasibility measures, while repeated measures ANOVAs were used to examine changes in the PM outcomes. RESULTS: A total of 88.2 % of the TPMI group completed all eight sessions, with moderate-to-high (≥7 out of 10) treatment credibility/expectancy and satisfaction reported by 93.3 % and 86.7 %, respectively. While there were no significant effects on overall PM, the TPMI group had an improvement in objective time-based PM after adjusting for baseline differences (F(1,29) = 4.61, p = 0.040; d = 0.80). Furthermore, the TPMI group had a significant reduction in the number of time-based loss of content errors compared to the Control group, which remained significant after covariate adjustment (F(1,25) = 4.29, p = 0.049; d = 0.83). CONCLUSIONS: TPMI is a feasible intervention, with high completion rates and moderate-to-high treatment ratings, that can be delivered remotely. Early evidence shows its potential benefit for improving time-based PM, a particular concern for PwMS, which should be further evaluated in a larger clinical trial.

Robot-assisted therapy for long-term upper-limb impairment after stroke.

BACKGROUND: Effective rehabilitative therapies are needed for patients with long-term deficits after stroke. METHODS: In this multicenter, randomized, controlled trial involving 127 patients with moderate-to-severe upper-limb impairment 6 months or more after a stroke, we randomly assigned 49 patients to receive intensive robot-assisted therapy, 50 to receive intensive comparison therapy, and 28 to receive usual care. Therapy consisted of 36 1-hour sessions over a period of 12 weeks. The primary outcome was a change in motor function, as measured on the Fugl-Meyer Assessment of Sensorimotor Recovery after Stroke, at 12 weeks. Secondary outcomes were scores on the Wolf Motor Function Test and the Stroke Impact Scale. Secondary analyses assessed the treatment effect at 36 weeks. RESULTS: At 12 weeks, the mean Fugl-Meyer score for patients receiving robot-assisted therapy was better than that for patients receiving usual care (difference, 2.17 points; 95% confidence interval [CI], -0.23 to 4.58) and worse than that for patients receiving intensive comparison therapy (difference, -0.14 points; 95% CI, -2.94 to 2.65), but the differences were not significant. The results on the Stroke Impact Scale were significantly better for patients receiving robot-assisted therapy than for those receiving usual care (difference, 7.64 points; 95% CI, 2.03 to 13.24). No other treatment comparisons were significant at 12 weeks. Secondary analyses showed that at 36 weeks, robot-assisted therapy significantly improved the Fugl-Meyer score (difference, 2.88 points; 95% CI, 0.57 to 5.18) and the time on the Wolf Motor Function Test (difference, -8.10 seconds; 95% CI, -13.61 to -2.60) as compared with usual care but not with intensive therapy. No serious adverse events were reported. CONCLUSIONS: In patients with long-term upper-limb deficits after stroke, robot-assisted therapy did not significantly improve motor function at 12 weeks, as compared with usual care or intensive therapy. In secondary analyses, robot-assisted therapy improved outcomes over 36 weeks as compared with usual care but not with intensive therapy. (ClinicalTrials.gov number, NCT00372411.)

The Gulf War era multiple sclerosis cohort: age and incidence rates by race, sex and service.

We characterize here a new nationwide incident cohort of multiple sclerosis from the US military-veteran population. This cohort provides an update to the only other US nationwide incidence study of multiple sclerosis performed during the 1970s. Medical records and data from the Department of Defense and Department of Veterans Affairs for cases of multiple sclerosis who served in the military between 1990, the start of the Gulf War era, and 2007 and who were service-connected for this disorder by the Department of Veterans Affairs from 1990 on, were reviewed. A total of 2691 patients were confirmed as having multiple sclerosis: 2288 definite, 190 possible, 207 clinically isolated syndrome and six neuromyelitis optica. Overall racial categories were White, Black and other, which included all Hispanics. There were 1278 White males and 556 females; 360 Black males and 296 females; and 200 others, 153 (77%) of whom were Hispanic. Mean age at onset of 30.7 years did not differ significantly by race or sex. Age at onset was 17-50 years in 99%, the same age range as 99% of the military. Average annual age specific (age 17-50 years) incidence rates per 100 000 for the entire series were 9.6 with 95% confidence interval of 9.3-10.0. Rates for Blacks were highest at 12.1 with confidence interval 11.2-13.1, Whites were 9.3 (interval 8.9-9.8) and others 6.9 (interval 6.0-7.9). For 83 Hispanics defined for 2000-07, the rate was 8.2 (interval 6.5-10.1). Much smaller numbers gave rates of 3.3 for Asian/Pacific Islanders and 3.1 for native Americans. Rates by sex for Whites were 7.3 and 25.8 male and female, respectively, for Blacks 8.4 and 26.3, and for Hispanics 6.6 and 17.0. Rates by service were high for Air Force (10.9) and Army (10.6), medium for Navy (9.1) and Coast Guard (7.9), and low for Marines (5.3). Relative risk of multiple sclerosis was 3.39 female:male and 1.27 Black:White. These new findings indicate that females of all races now have incidence rates for multiple sclerosis some three times those of their male counterparts and that among these groups, Blacks have the highest and others (probably including Hispanics) the lowest incidence rates regardless of sex or service. The low rate for Marines is unexplained. This Gulf War era multiple sclerosis cohort provides a unique resource for further study.

Identifying prospective memory deficits in multiple sclerosis: Preliminary evaluation of the criterion and ecological validity of a single item version of the memory for intentions test (MIST).

Objectives: Difficulties with prospective memory (PM) are not routinely assessed in persons with multiple sclerosis (MS) even though they can impact daily functioning. This study aimed to examine the preliminary criterion and ecological validity of a highly abbreviated Memory for Intentions Test (MIST) intended to serve as an initial screening of PM in persons with MS. Methods: Participants (n = 112) were classified as impaired if they performed 1.5 standard deviations below the normative mean on the MIST. Individual MIST trials with adequate difficulty and discriminability were examined using receiver operating characteristic analyses, with their classification accuracies, sensitivities, and specificities compared to each other. Regressions were run to evaluate their ecological validity, with appointment attendance and employment as the outcomes. Results: Two trials had a classification accuracy of ≥80%: Trial 3 (79% sensitivity, 84% specificity) and Trial 4 (57% sensitivity, 91% specificity). These two trials had comparable specificity (p=.127), with Trial 3 having slightly higher sensitivity (p=.083). Only Trial 4 was significantly associated with appointment attendance (b = 1.63, p=.047) and unemployment (aOR = 11.20, p=.027). Discussion:Trial 4 of the MIST, a verbal task with a time-based cue that requires participants to complete a pre-specified response after a 15-minute delay, has the potential to be a screener for PM.

Appointment attendance behaviors in multiple sclerosis: Understanding the factors that differ between no shows, short notice cancellations, and attended appointments.

BACKGROUND: There has yet to be an examination of how appointment attendance behaviors in multiple sclerosis (MS) are related to scheduling metrics and certain demographic, clinical, and behavioral factors such as cognitive functioning and personality traits. This study aimed to examine the factors that differ between no shows (NS), short notice cancellations (SNC), and attended appointments. METHODS: Participants (n = 110) were persons with MS who were enrolled in a larger cross-sectional study, during which they completed a battery of neuropsychological measures. Data about their appointments in three MS-related clinics the year prior to their study evaluation were extracted from the medical record. Bivariate analyses were done, with post-hoc tests conducted with Bonferroni corrections if there was an overall group difference. RESULTS: A higher number of SNC were noted during the winter, with 22.4% being due to the weather. SNC were also more common on Thursdays, but less frequent during the early morning time slots (7am to 9am). In contrast, NS were associated with lower annual income, weaker healthcare provider relationships, lower self-efficacy, higher levels of neuroticism, depressive symptom severity, and health distress, and greater cognitive difficulties, particularly with prospective memory. CONCLUSIONS: While SNC are related to clinic structure and situational factors like the weather, NS may be more influenced by behavioral issues, such as difficulty remembering an appointment and high levels of distress. These findings highlight potential targets for reducing the number of missed appointments in the clinic, providing opportunities for improved healthcare efficiency and most importantly health.

Using participatory action research to develop a new self-management program: Results from the design stage of Managing My MS My Way.

BACKGROUND: Self-management programs have been used with success in several clinical populations, and there is a growing body of evidence to support their use among persons with multiple sclerosis (MS). This group aimed to develop a novel self-management program, Managing My MS My Way (M4W), which is based in social cognitive theory and contains evidence-based strategies that have been shown to be effective for persons with MS. Furthermore, persons with MS would serve as stakeholders throughout the development process to ensure that the program would be useful and encourage adoption. This paper outlines the initial development stages of M4W, including determining 1) stakeholders' interest in a self-management program, 2) the general focus of the program, 3) the delivery method of the program, 4) the content of the program, and 5) potential barriers and adaptations. METHODS: A three-stage study consisting of an anonymous survey (n = 187) to determine interest, topic, and delivery format; semi-structured interviews (n = 6) to follow-up on the survey results; and semi-structured interviews (n = 10) to refine the content and identify barriers. RESULTS: Over 80% of survey participants were somewhat or very interested in a self-management program. Fatigue was the topic with the greatest amount of interest (64.7%). An internet-based program (e.g., mobile health or mHealth) was the most preferred delivery method (37.4%), with the first group of stakeholders proposing a module-based system with an initial in-person orientation session. The second group of stakeholders were overall enthusiastic about the program, giving moderate to high confidence scores for each of the proposed interventional strategies. Suggestions included skipping sections that were not applicable to them, setting reminders, and seeing their progress (e.g., visualizing their fatigue scores as they move through the program). In addition, stakeholders recommended larger font sizes and speech-to-text entry. CONCLUSIONS: Input from the stakeholders has been incorporated into the prototype of M4W. The next steps will be to test this prototype with another group of stakeholders to assess its initial usability and identify issues before developing the functional prototype.

Processing speed and memory test performance are associated with different brain region volumes in Veterans and others with progressive multiple sclerosis.

Background: Cognitive dysfunction and brain atrophy are both common in progressive multiple sclerosis (MS) but are seldom examined comprehensively in clinical trials. Antioxidant treatment may affect the neurodegeneration characteristic of progressive MS and slow its symptomatic and radiographic correlates. Objectives: This study aims to evaluate cross-sectional associations between cognitive battery components of the Brief International Cognitive Assessment for Multiple Sclerosis with whole and segmented brain volumes and to determine if associations differ between secondary progressive (SPMS) and primary progressive (PPMS) MS subtypes. Design: The study was based on a baseline analysis from a multi-site randomized controlled trial of the antioxidant lipoic acid in veterans and other people with progressive MS (NCT03161028). Methods: Cognitive batteries were conducted by trained research personnel. MRIs were processed at a central processing site for maximum harmonization. Semi-partial Pearson's adjustments evaluated associations between cognitive tests and MRI volumes. Regression analyses evaluated differences in association patterns between SPMS and PPMS cohorts. Results: Of the 114 participants, 70% had SPMS. Veterans with MS made up 26% (n = 30) of the total sample and 73% had SPMS. Participants had a mean age of 59.2 and sd 8.5 years, and 54% of them were women, had a disease duration of 22.4 (sd 11.3) years, and had a median Expanded Disability Status Scale of 6.0 (with an interquartile range of 4.0-6.0, moderate disability). The Symbol Digit Modalities Test (processing speed) correlated with whole brain volume (R = 0.29, p = 0.01) and total white matter volume (R = 0.33, p < 0.01). Both the California Verbal Learning Test (verbal memory) and Brief Visuospatial Memory Test-Revised (visual memory) correlated with mean cortical thickness (R = 0.27, p = 0.02 and R = 0.35, p < 0.01, respectively). Correlation patterns were similar in subgroup analyses. Conclusion: Brain volumes showed differing patterns of correlation across cognitive tasks in progressive MS. Similar results between SPMS and PPMS cohorts suggest combining progressive MS subtypes in studies involving cognition and brain atrophy in these populations. Longitudinal assessment will determine the therapeutic effects of lipoic acid on cognitive tasks, brain atrophy, and their associations.

Modifiable comorbidities and disability in multiple sclerosis.

Multiple sclerosis is a common neurological disease that results in disability in early adulthood that may progress through a relatively normal lifespan. Other comorbid health conditions can increase the likelihood of progression of MS and independently contribute to limitations in activities and social participation. We examine common modifiable health conditions and behaviors, including hypertension, obesity, diabetes mellitus, alcohol, and smoking to determine their impacts on MS and disability. Appropriate identification and treatment can improve health status, diminish disability, and improve quality of life.

Comorbidities as predictors of all-cause emergency department utilization among veterans with multiple sclerosis.

BACKGROUND: While comorbidities have been associated with all-cause hospitalizations among persons with multiple sclerosis (MS), there has been no examination of their role in all-cause emergency department (ED) utilization. As such, this study aimed to determine if the presence of comorbidities increases the odds of ED usage in a national sample of Veterans with MS. METHODS: Data were extracted retrospectively from the Veterans Affairs (VA) MS Center of Excellence Data Repository, an electronic health record-based dataset. Veterans who had at least one outpatient visit in 2013, were alive in 2015, and were initially prescribed a disease modifying therapy were included in the dataset (n = 3,742). Current Procedural Terminology codes were used to determine if participants had at least one ED visit during a 24-month time frame beginning 1/1/2013. Comorbidities were identified using ICD-9 codes present before 2013. Separate logistic regressions were conducted for the overall number of comorbidities and categorized comorbidities, adjusting for age, race, and sex. RESULTS: Nearly 32% (n = 1,191) had at least one ED visit, with those Veterans having an average of 6.67 (SD=3.32) comorbidities. After adjusting for demographics, the number of comorbidities was a significant predictor of ED usage (aOR=1.20; 95% CI: 1.17, 1.23, p<.001). Several comorbidities emerged as independent contributors. CONCLUSIONS: All-cause ED utilization is prevalent in MS, with usage increasing in the presence of other chronic conditions. These findings underscore the need to view long-term MS care through the lens of chronic disease management.

Moderators of Improvements in Fatigue Impact After a Self-management Intervention in Multiple Sclerosis: A Secondary Analysis of a Randomized Controlled Trial.

ABSTRACT: Fatigue is one of the most common and disabling symptoms of multiple sclerosis. A recent randomized controlled trial comparing a fatigue self-management program and a general multiple sclerosis education program found that both programs improved fatigue in participants with multiple sclerosis. Participants were randomized to a self-management program (fatigue: take control, n = 109) or a multiple sclerosis education program (multiple sclerosis: take control, n = 109). This secondary analysis of that trial used multilevel moderation analysis to examine moderators of treatment-related effects on fatigue (Modified Fatigue Impact Scale) from baseline through the 6-mo follow-up. The following potential treatment moderators were examined: age, sex, cohabitation/marital status, and baseline levels of self-efficacy, depression symptoms, and sleep quality. Cohabitation status (living with or without a spouse/partner) interacted with intervention group and time to predict fatigue impact (P = 0.04). Fatigue: take control participants who lived with a spouse/partner showed a marginal effect in greater rate of improvement in fatigue compared with those who lived alone (P = 0.08). However, rates of improvement in fatigue in multiple sclerosis: take control participants were similar in those living with or without a spouse/partner. These findings suggest that living with a spouse or partner may facilitate benefit from self-management interventions for multiple sclerosis-related fatigue. Future research should investigate the contribution of supportive others in self-management of fatigue in multiple sclerosis.

An economic analysis of robot-assisted therapy for long-term upper-limb impairment after stroke.

BACKGROUND AND PURPOSE: Stroke is a leading cause of disability. Rehabilitation robotics have been developed to aid in recovery after a stroke. This study determined the additional cost of robot-assisted therapy and tested its cost-effectiveness. METHODS: We estimated the intervention costs and tracked participants' healthcare costs. We collected quality of life using the Stroke Impact Scale and the Health Utilities Index. We analyzed the cost data at 36 weeks postrandomization using multivariate regression models controlling for site, presence of a prior stroke, and Veterans Affairs costs in the year before randomization. RESULTS: A total of 127 participants were randomized to usual care plus robot therapy (n=49), usual care plus intensive comparison therapy (n=50), or usual care alone (n=28). The average cost of delivering robot therapy and intensive comparison therapy was $5152 and $7382, respectively (P<0.001), and both were significantly more expensive than usual care alone (no additional intervention costs). At 36 weeks postrandomization, the total costs were comparable for the 3 groups ($17 831 for robot therapy, $19 746 for intensive comparison therapy, and $19 098 for usual care). Changes in quality of life were modest and not statistically different. CONCLUSIONS: The added cost of delivering robot or intensive comparison therapy was recuperated by lower healthcare use costs compared with those in the usual care group. However, uncertainty remains about the cost-effectiveness of robotic-assisted rehabilitation compared with traditional rehabilitation. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00372411.