National estimates of self-reported sitting time in adults with multiple sclerosis.

BACKGROUND: Limited data exist on the prevalence and distribution of sedentary behavior (SB) in multiple sclerosis (MS). OBJECTIVE: The objective of this paper is to describe sitting time as a metric of SB in a large national sample of people with MS. METHODS: A total of 8004 individuals from the North American Research Committee on MS (NARCOMS) Registry completed the sitting time question from the International Physical Activity Questionnaire in spring 2015. We present descriptive data on sitting time for the total sample and across sociodemographic, clinical, and behavioral characteristics. RESULTS: The final sample included 6483 individuals. Of these, 36.7% were classified with mild disability, 24.7% with moderate disability, and 38.6% with severe disability. Median sitting time for the total sample was 480 min/day (P25 = 310 min/day, P75 = 720 min/day). Sitting time was highest for individuals with MS who were male (540 min/day), not married (540 min/day), had a disease duration >30 years (540 min/day), were underweight (540.5 min/day), had an annual income of < $15,000 (585 min/day), presented with a progressive form of MS (600 min/day), were classified as insufficiently active (600 min/day), or presented with severe disability (661 min/day). CONCLUSION: Sitting time is twice as high in individuals with MS compared to the general population (240 min/day).

Cumulative impact of comorbidity on quality of life in MS.

BACKGROUND: Little is known about the impact of comorbidity on health-related quality of life (HRQOL) in multiple sclerosis (MS). We investigated the association of comorbidity and health-related HRQOL among participants in the North American Research Committee on Multiple Sclerosis (NARCOMS). MATERIALS AND METHODS: In 2006, we queried NARCOMS participants regarding physical and mental comorbidities and HRQOL, using the Short-Form 12. We summarized physical HRQOL using the aggregate Physical Component Scale (PCS-12) score and mental HRQOL using the aggregate Mental Component Scale (MCS-12) score. We assessed multivariable associations between comorbidity and HRQOL using a general linear model, adjusting for potential confounders. RESULTS: Among 8983 respondents, the mean (SD) PCS-12 was 36.9 (11.8) and MCS-12 was 45.6 (11.6). After adjustment for sociodemographic and clinical factors, participants with any physical comorbidity had a lower PCS-12 (37.2; 95% CI: 36.4-38.1) than those without any physical comorbidity (40.1; 95% CI: 39.0-41.1). As the number of physical comorbidities increased, PCS-12 scores decreased (r = -0.25; 95% CI: -0.23 to -0.27) indicating lower reported HRQOL. Participants with any mental comorbidity had a lower MCS-12 (40.7; 95% CI: 39.8-41.6) than those without any mental comorbidity (48.5; 95% CI: 47.7-49.4). CONCLUSIONS: Comorbidity is associated with reduced HRQOL in MS. Further research should evaluate whether more aggressive treatment of comorbidities improves the HRQOL of MS patients.

Association between comorbidity and clinical characteristics of MS.

BACKGROUND: Comorbidity may be associated with the clinical phenotype of disease and may affect prognostication and treatment decisions. Using the North American Research Committee on Multiple Sclerosis Registry, we described comorbidities present at onset and diagnosis of multiple sclerosis (MS) and examined whether comorbidities present at onset were associated with clinical course or age of MS symptom onset. METHODS: In 2006, 8983 participants reported their physical and mental comorbidities; smoking status; height; and past and present weight. We compared clinical course at onset and age of symptom onset by comorbidity status. RESULTS: At MS onset, a substantial proportion of participants had physical (24%) or mental (8.4%) comorbidities. The mean (SD) age of MS onset was 31.2 (9.0) years. Vascular, autoimmune, cancer, visual, and musculoskeletal comorbidities were associated with a later age of symptom onset. Among men and women, the odds of a relapsing course at onset were increased if mental comorbidities (OR 1.48; 1.08-2.01) were present at symptom onset. In women, gastrointestinal comorbidities (OR 1.78; 1.25-2.52) and obesity (OR 2.08 1.53-2.82) at MS onset were also associated with a relapsing course at onset. CONCLUSIONS: Comorbidity is frequently present at onset of MS and is associated with differences in clinical characteristics.

Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis.

BACKGROUND: Vascular comorbidity adversely influences health outcomes in several chronic conditions. Vascular comorbidities are common in multiple sclerosis (MS), but their impact on disease severity is unknown. Vascular comorbidities may contribute to the poorly understood heterogeneity in MS disease severity. Treatment of vascular comorbidities may represent an avenue for treating MS. METHODS: A total of 8,983 patients with MS enrolled in the North American Research Committee on Multiple Sclerosis Registry participated in this cohort study. Time from symptom onset or diagnosis until ambulatory disability was compared for patients with or without vascular comorbidities to determine their impact on MS severity. Multivariable proportional hazards models were adjusted for sex, race, age at symptom onset, year of symptom onset, socioeconomic status, and region of residence. RESULTS: Participants reporting one or more vascular comorbidities at diagnosis had an increased risk of ambulatory disability, and risk increased with the number of vascular conditions reported (hazard ratio [HR]/condition for early gait disability 1.51; 95% confidence interval [CI] 1.41-1.61). Vascular comorbidity at any time during the disease course also increased the risk of ambulatory disability (adjusted HR for unilateral walking assistance 1.54; 95% CI 1.44-1.65). The median time between diagnosis and need for ambulatory assistance was 18.8 years in patients without and 12.8 years in patients with vascular comorbidities. CONCLUSIONS: Vascular comorbidity, whether present at symptom onset, diagnosis, or later in the disease course, is associated with a substantially increased risk of disability progression in multiple sclerosis. The impact of treating vascular comorbidities on disease progression deserves investigation.

Impact of loss of mobility on instrumental activities of daily living and socioeconomic status in patients with MS.

OBJECTIVE: To assess the effects of mobility loss on instrumental activities of daily living (IADL) and socioeconomic status in multiple sclerosis (MS) patients. METHODS: Participants were active registrants in the North American Research Committee on Multiple Sclerosis registry completing the Fall 2006 (IADL analysis, n = 10,396) or Spring 2007 (socioeconomic analysis, n = 8180) surveys. Cross-sectional correlations and linear and logistic regression were performed using sociodemographic factors, mobility scales, and Patient Determined Disease Steps as independent variables and IADLs as the response. RESULTS: Mobility loss was significantly correlated with decreased IADL scores (r = -0.74; p < 0.0001); this correlation remained significant after adjustment for covariates. Mobility loss also negatively correlated with employment (r = -0.48 for women; r = -0.50 for men, both p < 0.0001) and annual income (r = -0.29; p < 0.0001). These correlations were all significant even with mild mobility loss. The relationships derived from the regression models suggest that the effect of mobility on employment is greater than the effect of demographic variables, and a small but direct effect on annual income that is independent of effects mediated through employment. The self-reported diagnosis of MS for study inclusion and use of single-item ordinal scales for mobility and disability can potentially be criticized as study limitations, although the diagnosis and the scales were previously validated. CONCLUSION: Mobility loss independently correlated with IADL, and associated with reduced socioeconomic status in people with MS. These correlations were significant with mild mobility loss, supporting early treatment.

The burden of mental comorbidity in multiple sclerosis: frequent, underdiagnosed, and undertreated.

BACKGROUND: Mental comorbidity is common in multiple sclerosis (MS), but some studies suggest that mental comorbidity may be underrecognized and undertreated. OBJECTIVE: Using the North American Research Committee on MS Registry, we assessed the frequency of mental comorbidities in MS and sociodemographic characteristics associated with diagnosis and treatment of depression. METHODS: We queried participants regarding depression, anxiety, bipolar disorder, and schizophrenia. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CESD); a score>or=21 indicated probable major depression. RESULTS: Mental comorbidity affected 4264 (48%) responders; depression most frequently (4012, 46%). Among participants not reporting mental comorbidity, 751 (16.2%) had CESD scores>or=21 suggesting undiagnosed depression. Lower socioeconomic status was associated with increased odds of depression (Income $15,000-30,000 vs >$100,000 OR 1.34; 1.11-1.62), undiagnosed depression (Income $15,000-30,000 vs >$100,000 OR 1.52; 1.08-2.13), and untreated depression (

Comorbidity delays diagnosis and increases disability at diagnosis in MS.

BACKGROUND: Comorbidity is common in the general population and is associated with adverse health outcomes. In multiple sclerosis (MS), it is unknown whether preexisting comorbidity affects the delay between initial symptom onset and diagnosis ("diagnostic delay") or the severity of disability at MS diagnosis. OBJECTIVES: Using the North American Research Committee on Multiple Sclerosis Registry, we assessed the association between comorbidity and both the diagnostic delay and severity of disability at diagnosis. In 2006, we queried participants regarding physical and mental comorbidities, including date of diagnosis, smoking status, current height, and past and present weight. Using multivariate Cox regression, we compared the diagnostic delay between participants with and without comorbidity at diagnosis. We classified participants enrolled within 2 years of diagnosis (n = 2,375) as having mild, moderate, or severe disability using Patient Determined Disease Steps, and assessed the association of disability with comorbidity using polytomous logistic regression. RESULTS: The study included 8,983 participants. After multivariable adjustment for demographic and clinical characteristics, the diagnostic delay increased if obesity, smoking, or physical or mental comorbidities were present. Among participants enrolled within 2 years of diagnosis, the adjusted odds of moderate as compared to mild disability at diagnosis increased in participants with vascular comorbidity (odds ratio [OR] 1.51, 95% CI 1.12-2.05) or obesity (OR 1.38, 95% CI 1.02-1.87). The odds of severe as compared with mild disability increased with musculoskeletal (OR 1.81, 95% CI 1.25-2.63) or mental (OR 1.62, 95% CI 1.23-2.14) comorbidity. CONCLUSIONS: Both diagnostic delay and disability at diagnosis are influenced by comorbidity. The mechanisms underlying these associations deserve further investigation.

High frequency of adverse health behaviors in multiple sclerosis.

BACKGROUND: Health behaviors influence chronic disease risks in the general population, and may influence health outcomes independently of comorbid diseases. Health behaviors receive less attention in multiple sclerosis (MS) than in the general population. We assessed health behaviors among participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry and the demographic characteristics associated with particular health behaviors. METHODS: In October 2006, we surveyed NARCOMS participants regarding smoking using questions from the Behavioral Risk Factor Surveillance Survey; physical activity using questions from the PEPI study, alcohol use using the AUDIT-C; and height and weight. To determine the independent demographic predictors of health behaviors, we used multivariable logistic regression, either binary or polytomous as appropriate. RESULTS: Of 8983 responders, 4867 (54.2%) ever smoked; 1542 (17.3%) currently smoked. On the basis of the AUDIT-C, 1632 (18.2%) were at risk for alcohol abuse or dependence. A quarter of participants were obese (n = 2269), and 2780 (31.3%) were overweight. Fewer than 25% of participants reported moderate or heavy leisure-time physical activity. Generally, lower socioeconomic status was associated with a higher frequency of adverse health behaviors accounting for other demographic factors. With increasing levels of disability, the reported intensity of physical activity was lower, and the frequency of overweight or obesity was higher. CONCLUSIONS: Patients with MS exhibit frequent adverse health behaviors, increasing the risk of other chronic diseases. Further research is needed to determine how these behaviors influence disability progression, quality of life, and other MS-related outcomes.

Comorbidity, socioeconomic status and multiple sclerosis.

OBJECTIVE: Multiple sclerosis (MS) is associated with substantial morbidity. The impact of comorbidity on MS is unknown, but comorbidity may explain some of the unpredictable progression. Comorbidity is common in the general population, and is associated with adverse health outcomes. To begin understanding the impact of comorbidity on MS, we need to know the breadth, type, and frequencies of comorbidities among MS patients. Using the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry, we aimed to describe comorbidities and their demographic predictors in MS. METHODS: In October 2006, we queried NARCOMS participants regarding physical comorbidities. Of 16,141 participants meeting the inclusion criteria, 8983 (55.7%) responded. RESULTS: Comorbidity was relatively common; if we considered conditions which are very likely to be accurately self-reported, then 3280 (36.7%) reported at least one physical comorbidity. The most frequently reported comorbidities were hypercholesterolemia (37%), hypertension (30%), and arthritis (16%). Associated with the risk of comorbidity were being male [females vs. males, odds ratio (OR) 0.77; 0.69-0.87]; age (age >60 years vs. age < or = 44 years, OR 5.91; 4.95-7.06); race (African Americans vs. Whites, OR 1.46; 1.06-2.03); and socioeconomic status (Income <$15,000 vs. Income >$100,000, OR 1.37; 1.10-1.70). CONCLUSIONS: Comorbidity is common in MS and similarly associated with socioeconomic status.

APOE epsilon 4 allele is associated with cognitive impairment in patients with multiple sclerosis.

BACKGROUND: The role of apolipoprotein E (APOE) polymorphism has been well recognized in other cognitive neurodegenerative disorders, such as Alzheimer disease. Its role in multiple sclerosis (MS) is less clear, though studies indicate that 40% to 60% of patients with MS have evidence of cognitive impairment. OBJECTIVE: To determine whether there is an association between APOE epsilon 4 and cognitive deficits in MS. METHODS: We performed a standardized battery of neuropsychological tests investigating the four cognitive domains commonly impaired in MS and assessed the association of the presence of APOE epsilon 4 with cognition in MS. RESULTS: A strong association was found between the presence of APOE epsilon 4 and cognitive deficits in patients with MS, particularly in the domains of learning and memory. This association was strongest in our youngest cohort (age 31 to 40) of patients with MS. CONCLUSIONS: APOE epsilon 4 is significantly associated with cognitive impairment in patients with multiple sclerosis (MS). However, the modest effects do not justify APOE genotyping of patients with MS in clinical practice.

Disparities in the management of multiple sclerosis-related bladder symptoms.

BACKGROUND: Participants enrolled in the North American Research Committee on Multiple Sclerosis (NARCOMS) registry report disability status using Performance Scales (PS), a self-report measure. The bladder/bowel subscale (PSB) of PS has not been validated. It is also unknown whether ethnic or socioeconomic disparities exist in bladder care. OBJECTIVE: We aimed to validate the bladder/bowel subscale used by the NARCOMS registry and to describe urologic symptoms, investigations, and treatments received by registry participants. METHODS: In the Fall 2005 update questionnaire, we collected the Bowel Control Scale (BWCS) and Urogenital Distress Inventory-6 (UDI-6) as criterion measures and urologic investigations and treatments. We measured associations between investigations, treatments, and symptoms with clinical and sociodemographic variables using chi(2) tests for categorical variables and Kruskal-Wallis tests for continuous variables, followed by multivariable logistic regression. RESULTS: Nine thousand six hundred eighty-eight participants completed the survey. For the UDI-6, the median (interquartile range) score was 33.3 (16.7 to 50.0), for the BWCS 3 (1 to 6), and for the PSB 1 (1 to 3). The correlation between the PSB and the UDI-6 was r = 0.67 and between the PSB and the BWCS r = 0.53 (both p < 0.0001). Participants had increased odds of receiving medication for bladder symptoms if they had health insurance (odds ratio [OR] 1.90; 1.07 to 3.35). Participants who were white (OR 1.5; 1.16 to 1.94) and had health insurance (OR 2.0; 1.3 to 3.07) had increased odds of undergoing urologic investigations. CONCLUSION: The Performance Scales bladder question has adequate criterion and construct validity in multiple sclerosis (MS). There are ethnic and socioeconomic disparities in bladder management in MS.

Validation of the NARCOMS registry: diagnosis.

The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry is a patient registry, wherein the diagnoses of multiple sclerosis (MS) are unverified. We compared self-reported diagnoses of registry participants to physician-reported diagnoses, and with diagnoses based on medical records review. Registry participants with more than one of the following: age of onset <10 or >50 years, no bladder symptoms or fatigue, or zero or more than four relapses in the last year, were considered atypical. All others were considered typical. We sent letters to participants describing the study, surveyed treating physicians regarding the participants' diagnosis, and reviewed medical records. Diagnosis was classified by the McDonald and Poser criteria. Of the 240 participants sampled, 109 were in active registry status with accurate contact information. Of these, 52 consented, 29 refused and 28 did not respond (weighted response rate 76.3+/-4.5%). Some 37 of 38 physician surveys confirmed the diagnosis of MS (98.8+/-1.2%). After reviewing 41 medical records, we classified 53.2+/-8.9% of participants as definite MS, 16.9+/-6.8% as possible MS, while the remainder had insufficient data for diagnostic confirmation. We confirmed a diagnosis of MS in 98.7+/-1.3% of participants based on records review, physician survey or telephone interview, supporting the validity of the diagnoses reported by NARCOMS participants.

Does multiple sclerosis-associated disability differ between races?

OBJECTIVE: To investigate differences in disability between African American and Caucasian patients with multiple sclerosis (MS) by comparing the relationship between current age and disability between races and by assessing the effect of adjustment for socioeconomic status (SES) on the associations. METHODS: The authors selected US participants from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry with an age at symptom onset of 10 to 60 years, who reported their race as Caucasian or African American (n = 21,557). They classified participants as having mild, moderate, or severe disability in the domains of mobility, hand function, cognition, and vision using Patient Determined Disease Steps and Performance Scales and assessed the association of disability with race using polytomous logistic regression. RESULTS: Disability increased more rapidly with increasing disease duration in older patients, but there was no interaction between race and age. African Americans had increased odds of severe vs mild disability in all four domains (odds ratio [OR] [95% CI]: hand 1.35 [1.10 to 1.64]; vision 1.75 [1.37 to 2.27]; cognition 1.32 [1.04 to 1.67]; mobility 1.32 [1.11 to 1.56]). Adjustment for all covariates, including SES, attenuated these associations (OR [95% CI]: hand 1.27 [1.00 to 1.61]; vision 1.59 [1.19 to 2.08]; cognition 0.98 [0.74 to 1.30]; mobility 1.37 [1.11 to 1.67]). Lack of adjustment for SES produced stronger associations. After enrollment in NARCOMS, disability progression did not differ between the groups. CONCLUSIONS: African Americans experience greater multiple sclerosis-associated disability than Caucasians. Failure to account for socioeconomic status leads to overestimation of these differences. Disease progression is similar in African Americans and Caucasians after diagnosis.

Changes in the ascertainment of multiple sclerosis.

OBJECTIVE: With diagnostic criteria alterations, increased MRI availability, and awareness of therapies, temporal changes in incidence and prevalence rates may occur, with an increase in the proportion of mildly affected persons diagnosed with multiple sclerosis (MS). The authors assessed temporal trends in the delay from symptom onset to diagnosis (DONDX), and determined whether the degree of disability at diagnosis differs by year of symptom onset (YONSET), using the NARCOMS Registry. METHODS: The authors selected US participants with an age at symptom onset of 10 to 60 years, and YONSET > or = 1980 (n = 16,581). The authors divided YONSET into 5-year groups and compared DONDX between groups using multivariate Cox regression. The authors classified participants enrolled within 2 years of diagnosis (n = 5,548) as having mild, moderate, or severe disability using Patient Determined Disease Steps, and assessed the association of disability with YONSET using polytomous logistic regression. RESULTS: DONDX decreased with later YONSET (r = -0.43, p < 0.0001). This association remained after adjustment for demographic factors in a multivariate Cox model. Later YONSET was associated with increased odds of having mild disability at diagnosis as compared to severe disability (OR = 1.10 per year; 1.09 to 1.11). CONCLUSION: The delay from symptom onset to diagnosis is steadily decreasing in MS. An increasing proportion of patients with MS have mild disability at diagnosis after accounting for confounders. As the effectiveness of therapies is influenced by disease duration, this has implications for comparison of treatment effects in modern clinical trials to earlier study results.

A 2-km walking test for assessing the cardiorespiratory fitness of healthy adults.

A simple walking test was developed with 159 (females = 80, males = 79) healthy 20-65-year-old subjects. All the subjects first walked the distances of 1.0, 1.5 and 2.0 km on a flat dirt road. Half of the participants were tested in the laboratory for maximal oxygen uptake (VO2max), and the 2-km test was repeated again twice. In a comparison of the three distances, the 2-km test was repeatable, the most preferable subjectively and the most accurate in predicting VO2max. A sex-specific prediction model including walking time, heart rate at the end of the walk, age and body mass index predicted 73-75% of the variance in VO2max (ml.kg-1.min-1) and that with body weight 66-76%, with a standard error of estimate of the order of 9-15% of the mean. The cross-validation of the models yielded reasonable accuracy in obese men and women and in moderately active men, and less accuracy in moderately active women and highly active men. These results suggest that a fast 2-km walk supplemented with simple measurements is a feasible and accurate alternative for determining the cardiorespiratory fitness of healthy adults.