Effects of physical comorbidities on disability progression in multiple sclerosis.

OBJECTIVE: To examine the association between physical comorbidities and disability progression in multiple sclerosis (MS). METHODS: We conducted a retrospective cohort study using linked health administrative and clinical databases in 2 Canadian provinces. Participants included adults with incident MS between 1990 and 2010 who entered the cohort at their MS symptom onset date. Comorbidity status was identified with validated algorithms for health administrative data and was measured during the 1 year before study entry and throughout the study period. The outcome was the Expanded Disability Status Scale (EDSS) score as recorded at each clinic visit. We used generalized estimating equations to examine the association between physical comorbidities and EDSS scores over time, adjusting for sex, age, cohort entry year, use of disease-modifying drugs, disease course, and socioeconomic status. Meta-analyses were used to estimate overall effects across the 2 provinces. RESULTS: We identified 3,166 individuals with incident MS. Physical comorbidity was associated with disability; with each additional comorbidity, there was a mean increase in the EDSS score of 0.18 (95% confidence interval [CI] 0.09-0.28). Among specific comorbidities, the presence of ischemic heart disease (IHD) or epilepsy was associated with higher EDSS scores (IHD 0.31, 95% CI 0.01-0.61; epilepsy 0.68, 95% CI 0.11-1.26). CONCLUSIONS: Physical comorbidities are associated with an apparent increase in MS disability progression. Appropriate management of comorbidities needs to be determined to optimize outcomes.

Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study.

BACKGROUND: Degenerative processes in neurodegenerative diseases can start years before clinical manifestation. We aimed to establish whether a multiple sclerosis prodromal period exists by examining patterns of health-care use before a first demyelinating event. METHODS: In this matched cohort study, we used data from linked health administrative and clinical databases from four Canadian provinces (British Columbia, Saskatchewan, Manitoba, and Nova Scotia) to compare hospital, physician, and prescription use data from people with multiple sclerosis and matched general population controls in the 5 years before the first demyelinating disease claim (health administrative index date) or clinically reported symptom onset (clinical index date). Rate ratios (RRs) were estimated using negative binomial regression and combined across provinces using random effect models. The primary outcome was all-cause use of health care during each of the 5 years before the health administrative or clinical index date. FINDINGS: The health administrative cohort included 14 428 multiple sclerosis cases and 72 059 matched controls for whom data were available between April, 1984, and April, 2014. Annual health-care use increased steadily between 5 years and 1 year before the first demyelinating disease claim in people with multiple sclerosis compared with controls (from RR 1·26 [95% CI 1·16-1·36] to 1·78 [1·50-2·10] for hospital admissions; from 1·24 [1·16-1·32] to 1·88 [1·72-2·07] for physician claims; and from 1·23 [1·06-1·41] to 1·49 [1·41-1·59] for prescriptions, assessed as drug classes). Similar patterns for physician claims and prescriptions were observed in the cohort with available clinical symptom onset (3202 individuals with multiple sclerosis and 16 006 controls), although the differences in use in each of the 5 years mostly did not reach statistical significance. INTERPRETATION: More frequent use of health care in patients with multiple sclerosis than in controls in the 5 years before a first demyelinating event, according to health administrative data, suggests the existence of a measurable multiple sclerosis prodrome. These findings have clinical and research implications, including the establishment of an earlier window of opportunity to identify and potentially treat multiple sclerosis. FUNDING: National Multiple Sclerosis Society.

Examining the effects of comorbidities on disease-modifying therapy use in multiple sclerosis.

OBJECTIVE: Comorbidities are common in multiple sclerosis (MS) and adversely affect health outcomes. However, the effect of comorbidity on treatment decisions in MS remains unknown. We aimed to examine the effects of comorbidity on initiation of injectable disease-modifying therapies (DMTs) and on the choice of the initial DMT in MS. METHODS: We conducted a retrospective observational analysis using population-based health administrative and linked clinical databases in 3 Canadian provinces. MS cases were defined as any individual with ≥3 diagnostic codes for MS. Cohort entry (index date) was the first recorded demyelinating disease-related claim. The outcomes included choice of initial first-line DMTs and time to initiating a DMT. Logistic and Cox regression models were used to examine the association between comorbidity status and study outcomes, adjusting for sex, age, year of index date, and socioeconomic status. Meta-analysis was used to estimate overall effects across the 3 provinces. RESULTS: We identified 10,698 persons with incident MS, half of whom had ≥1 comorbidities. As the total number of comorbidities increased, the likelihood of initiating a DMT decreased. Comorbid anxiety and ischemic heart disease were associated with reduced initiation of a DMT. However, patients with depression were 13% more likely to initiate a DMT compared to those without depression at the index date (adjusted hazard ratio 1.13; 95% confidence interval 1.00-1.27). CONCLUSIONS: Comorbidities are associated with treatment decisions regarding DMTs in MS. A better understanding of the effects of comorbidity on effectiveness and safety of DMTs is needed.

The incidence and prevalence of multiple sclerosis in Nova Scotia, Canada.

BACKGROUND: Estimates of incidence and prevalence are needed to determine disease risk and to plan for health service needs. Although the province of Nova Scotia, Canada is located in a region considered to have a high prevalence of multiple sclerosis (MS), epidemiologic data are limited. OBJECTIVE: We aimed to validate an administrative case definition for MS and to use this to estimate the incidence and prevalence of MS in Nova Scotia. METHODS: We used provincial administrative claims data to identify persons with MS. We validated administrative case definitions using the clinical database of the province's only MS Clinic; agreement between data sources was expressed using a kappa statistic. We then applied these definitions to estimate the incidence and prevalence of MS from 1990 to 2010. RESULTS: We selected the case definition using ≥7 hospital or physician claims when >3 years of data were available, and ≥3 claims where less data were available. Agreement between data sources was moderate (kappa = 0.56), while the positive predictive value was high (89%). In 2010, the age-standardized prevalence of MS per 100,000 population was 266.9 (95% CI: 257.1- 277.1) and incidence was 5.17 (95% CI: 3.78-6.56) per 100,000 persons/year. From 1990-2010 the prevalence of MS rose steadily but incidence remained stable. CONCLUSIONS: Administrative data provide a valid and readily available means of estimating MS incidence and prevalence. MS prevalence in Nova Scotia is among the highest in the world, similar to recent prevalence estimates elsewhere in Canada.Incidence et prévalence de la sclérose en plaques en Nouvelle-Écosse, Canada.

Responsiveness of goal attainment scaling in a randomized controlled trial of comprehensive geriatric assessment.

BACKGROUND AND OBJECTIVE: Frail elderly patients have complex problems that require a multidimensional assessment and a range of treatment goals. Goal Attainment Scaling (GAS) measures multiple, individualized goals, but its responsiveness in comparative clinical trials has not been established. METHODS: We assessed the responsiveness of GAS in a randomized, controlled trial of an interdisciplinary Mobile Geriatric Assessment Team (MGAT) in 265 rural frail older adults. Sensitivity to change was compared with standard measures; clinical meaningfulness was assessed in relation to a patient and a blinded physician global measure. RESULTS: At 3 months follow-up, GAS was the most responsive measure (standardized response mean 1.22, Norman's responsiveness statistic 0.58) compared with the Barthel Index (1.13, 0.46), Physical Self-Maintenance Scale (0.10, 0.16, 0.02), Instrumental Activities of Daily Living (0.23, 0.00), and modified Spitzer Quality of Life Index (-0.04, 0.00). CONCLUSIONS: Only GAS detected clinically important change associated with the MGAT intervention in these frail elderly patients. Clinometric measures can offer a responsive means of evaluating complex interventions.