Denise Campagnolo

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.

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 ≥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 ≥21 suggesting undiagnosed depression. Lower socioeconomic status was associated with increased odds of depression (Income

Does multiple sclerosis–associated disability differ between races?

15,000–30,000 vs >

High frequency of adverse health behaviors in multiple sclerosis

100,000 OR 1.34; 1.11–1.62), undiagnosed depression (Income

Glatiramer acetate after induction therapy with mitoxantrone in relapsing multiple sclerosis

15,000–30,000 vs >

Changes in the ascertainment of multiple sclerosis

100,000 OR 1.52; 1.08–2.13), and untreated depression (<high school vs postgraduate degree OR 3.13; 1.65–5.99). Conclusions Mental comorbidity remains underdiagnosed and undertreated in MS. Patients of lower socioeconomic status bear a disproportionate share of the burden of depression.

Disparities in the management of multiple sclerosis–related bladder symptoms

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.

The impact of sexual dysfunction on health-related quality of life in people with 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.

The Multiple Sclerosis Intimacy and Sexuality Questionnaire — re-validation and development of a 15-item version with a large US sample

Forty relapsing multiple sclerosis patients with 1–15 gadolinium (Gd)-enhancing lesions on screening brain magnetic resonance imaging (MRI) and Expanded Disability Status Scale (EDSS) scores 0–6.5 were randomized to receive short-term induction therapy with mitoxantrone (three monthly 12 mg/m2 infusions) followed by 12 months of daily glatiramer acetate (GA) therapy 20 mg/day subcutaneously for a total of 15 months (M-GA, n = 21) or daily GA 20 mg/day for 15 months (GA, n = 19). MRI scans were performed at months 6, 9, 12 and 15. The primary measure of outcome was the incidence of adverse events; secondary measures included number of Gd-enhanced lesions, confirmed relapses and EDSS changes. Except age, baseline demographic characteristics were well matched in both treatment arms. Both treatments were safe and well tolerated. M-GA induction produced an 89% greater reduction (relative risk (RR) = 0.11, 95% confidence interval (CI): 0.04–0.36, p = 0.0001) in the number of Gd-enhancing lesions at months 6 and 9 and a 70% reduction (RR = 0.30, 95% CI: 0.11–0.86, p = 0.0147) at months 12 and 15 versus GA alone. Mean relapse rates were 0.16 and 0.32 in the M-GA and GA groups, respectively. Short-term immunosuppression with mitoxantrone followed by daily GA for up to 15 months was found to be safe and effective, with an early and sustained decrease in MRI disease activity.

Smoking Status over Two Years in Patients with 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 ≥ 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.