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ABSTRACT: Objectives: Hospital admissions are important surrogate measures for disease worsening and increased demand on healthcare resources; few studies have examined hospitalizations in multiple sclerosis (MS). We examined hospital admission rates and patterns in a large Canadian MS cohort. Study Design: Retrospective, observational study. Methods: Data from the British Columbia MS database were linked with hospital separation and registry administrative data, 1986 to 2008. Main outcomes included all-cause hospital admission rates and length of stay. The influence of time and patient characteristics was examined using multivariable regression models. Results: Overall rate of all-cause admissions was 32.4 per 100 MS patients. Rates decreased by 1.4% (adjusted incidence rate ratio [IRR] 0.986; 95% confidence interval [CI] 0.982-0.990) per year from 1986 onward. Higher admission rates were associated with older age (adjusted IRR 1.011; 95% CI 1.007-1.014), primary progressive MS (adjusted IRR 1.294; 95% CI 1.162-1.441), and a longer disease duration (adjusted IRR 1.030; 95% CI 1.027-1.034). Mean length of inpatient stay was 10.2 (standard deviation [SD] 24.8) days, and increased over time. Hospital stays were longer for older patients and those with a longer disease duration, but were not influenced by sex or disease course. Conclusions: Admission rates for MS patients have decreased since 1986, but length of stay has increased. Patients with a longer disease duration and those with primary progressive MS had higher rates of admission and longer stays. Understanding the impact of time and patient characteristics on hospitalizations is important for resource allocation planning and designing future research studies examining interventions and treatments for MS.
The American journal of managed care 11/2012; 18(11):735-42. · 2.46 Impact Factor
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ABSTRACT: Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established.
To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS.
Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts.
The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication.
The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results.
Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.
JAMA The Journal of the American Medical Association 07/2012; 308(3):247-56. · 30.03 Impact Factor
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ABSTRACT: Findings regarding cancer risk in people with multiple sclerosis have been inconsistent and few studies have explored the possibility of diagnostic neglect. The influence of a relapsing-onset versus primary progressive course on cancer risk is unknown. We examined cancer risk and tumour size at diagnosis in a cohort of patients with multiple sclerosis compared to the general population and we explored the influence of disease course. Clinical data of patients with multiple sclerosis residing in British Columbia, Canada who visited a British Columbia multiple sclerosis clinic from 1980 to 2004 were linked to provincial cancer registry, vital statistics and health registration data. Patients were followed for incident cancers between onset of multiple sclerosis, and the earlier of emigration, death or study end (31 December 2007). Cancer incidence was compared with that in the age-, sex- and calendar year-matched population of British Columbia. Tumour size at diagnosis of breast, prostate, colorectal and lung cancers were compared with population controls, matched for cancer site, sex, age and calendar year at cancer diagnosis, using the stratified Wilcoxon test. There were 6820 patients included, with 110 666 person-years of follow-up. The standardized incidence ratio for all cancers was 0.86 (95% confidence interval: 0.78-0.94). Colorectal cancer risk was also significantly reduced (standardized incidence ratio: 0.56; 95% confidence interval: 0.37-0.81). Risk reductions were similar by sex and for relapsing-onset and primary progressive multiple sclerosis. Tumour size was larger than expected in the cohort (P = 0.04). Overall cancer risk was lower in patients with multiple sclerosis than in the age-, sex- and calendar year matched general population. The larger tumour sizes at cancer diagnosis suggested diagnostic neglect; this could have major implications for the health, well-being and longevity of people with multiple sclerosis.
Brain 06/2012; 135(Pt 10):2973-9. · 9.46 Impact Factor
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ABSTRACT: Immunomodulatory drugs (IMDs) for multiple sclerosis (MS) have been available in Canada since 1995 and are currently the most commonly prescribed treatment for MS. However, relatively little is known about the long-term persistence to these drugs.
The purpose of this study was to describe patterns of, and factors associated with, long-term persistence to the first-line IMDs in an MS population in British Columbia, Canada.
Study data were collected from the British Columbia MS database. Adults from British Columbia with definite MS who were prescribed a first-line IMD (interferon beta-1b, interferon beta-1a [subcutaneous and intramuscular], and glatiramer acetate) from January 1, 1995, through December 31, 2008, were eligible for the study. Time to discontinuation of use of all first-line IMDs (ie, switching among IMD therapies was allowed) and the initially prescribed IMD was assessed using Kaplan-Meier survival analysis and multivariate Cox regression.
A total of 1896 patients were included. Mean (SD) age was 40.2 (9.5) years, and 75.1% were female. Median time to discontinuation of all first-line IMD therapies was 6.3 years (95% CI, 5.8-6.7 years). Patients with a longer disease duration and higher level of disability were at higher risk for discontinuing use of the IMDs. Age, sex, and the initial IMD were not associated with discontinuation. Persistence appeared to have decreased over time (P = 0.01 for trend). Median time to discontinued use of, or switching from, the initially prescribed IMD was 2.9 years (95% CI, 2.5-3.2 years).
Approximately half of the MS patients discontinued use of their IMD within 6 years. It is unknown whether this persistence is adequate because uncertainties remain regarding the optimal level of persistence to the IMDs. Further investigation is needed to examine why some individuals are more at risk for discontinuation of IMD therapy and why, in contrast to other chronic diseases, persistence to IMDs in patients with MS has not improved over time.
Clinical Therapeutics 02/2012; 34(2):341-50. · 2.32 Impact Factor
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JAMA The Journal of the American Medical Association 01/2012; 308(3):247-256. · 30.03 Impact Factor
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ABSTRACT: Recent natural history studies suggest that multiple sclerosis (MS) is a more slowly progressing disease than previously thought. These observations are from studies separated by time, geography and methodological approach.
We investigated whether MS disease progression has changed over time in British Columbia, Canada.
The British Columbia MS database was queried for relapsing-onset MS patients with symptom onset from 1975 to <1995, first assessed within 15 years from onset and with at least two Expanded Disability Status Scale (EDSS) scores. Latest follow-up was to 2009. Patients were grouped by 5-year onset intervals (1975 to <1980, 1980 to <1985, 1985 to <1990, 1990 to <1995). Outcome was defined as time to reach sustained and confirmed EDSS 6 within 15 years of disease duration. Kaplan-Meier analysis was used to compare: the proportion of patients reaching EDSS 6 (primary analysis) and the time to EDSS 6 (secondary analysis) across the time-period groups. Results: A total of 2236 relapsing-onset MS patients (73.4% female; mean age at onset: 32.3 ± 8.8 years) were included. No significant temporal trend was found in the proportion of patients reaching EDSS 6 within 15 years from onset (28.5%, 26.4%, 27.7%, 22.3% for intervals 1975 to <1980, 1980 to <1985, 1985 to <1990, 1990 to <1995, respectively; p = 0.09) or in survival curves for time to reach the outcome (p = 0.14).
Rates of disease progression remained relatively stable over two decades of MS onset in British Columbia, Canada. Our results suggest that differences in disease progression findings between natural history studies may be related to factors other than time period.
Multiple Sclerosis 09/2011; 18(4):442-50. · 4.26 Impact Factor
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ABSTRACT: The onset of secondary progression is a pivotal event in the course of relapsing-remitting (RR) multiple sclerosis (MS). Patients with secondary progressive MS (SPMS) experience continuous worsening of symptoms independent of the occurrence of relapses. Possible risk factors associated with the onset of SPMS remain under investigated in natural history studies of MS disease course.
We used Kaplan-Meier survival analyses and Cox regression models to investigate the influence of gender, onset age and onset symptoms on time to and age at SPMS in British Columbia (BC) MS patients with a RR disease onset who were not exposed to immunomodulatory drugs.
Of 5778 patients in the BCMS database with definite MS, 5207 (90%) had an RR onset. Median time to SPMS was 21.4 years (95% CI 20.6 to 22.2), reached at a median age of 53.7 years (95% CI 53.1 to 54.3). Male gender and motor onset symptoms were associated with a shorter time to and a younger age at SPMS. A younger age at disease onset was associated with a longer time to SPMS but also with a younger age at secondary progression. Other onset symptoms were not associated with time to, or age at, SPMS.
We identified three factors influencing the onset of SPMS in untreated patients with RRMS: motor onset symptoms and male gender were associated with both a shorter time to and a younger age at SPMS. A younger age at disease onset should not be viewed as indicating a better prognosis.
Journal of neurology, neurosurgery, and psychiatry 09/2010; 81(9):1039-43. · 4.87 Impact Factor
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ABSTRACT: Long referral and diagnostic delays can impact both the opportunity for early therapeutic intervention and estimates of MS incidence and prevalence. We investigated factors associated with diagnostic or referral delays within two geographically distinct MS Canadian cohorts and the association between referral delay and disability at first clinic visit. Adult-onset MS patients were selected from the population-based British Columbian MS (BCMS) (n=5705) and the clinic-based Hôpital Notre-Dame, Quebec (CHUM) (n=1489) databases. Referral delay (BCMS) and diagnostic delay (CHUM) were examined by sex, onset age, disease course (primary progressive (PPMS) vs. relapsing at onset), onset symptoms (BCMS only) and year of first clinic visit/diagnosis. Cohorts were analyzed separately by stratified analyses and multivariable linear modeling. The relationship between referral delay and initial disability was examined by multiple ordinal regression in the BCMS cohort. Younger at onset patients or those with PPMS exhibited significantly longer delays (p<0.001). Delays decreased over the 20+ year period, but reductions varied by clinical course, onset age and sex. Long referral delays were associated with greater disability at first clinic visit (p<0.001). If early intervention at mild disability levels is warranted in MS, then the extended delays to medical recognition for young adult-onset and PPMS patients must be addressed.
Journal of the neurological sciences 03/2010; 292(1-2):57-62. · 2.32 Impact Factor
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ABSTRACT: Primary progressive multiple sclerosis (PPMS) carries the worst prognosis of the multiple sclerosis (MS) subtypes and is currently untreatable. A previous analysis of the British Columbia MS database challenged the view that disability progression is rapid in PPMS, but identified few predictors of disease progression. Here, we extend previous analyses in an updated PPMS retrospective cohort study of prevalent cases.
We used Kaplan-Meier survival analyses and Cox regression models to investigate the influence of gender, age at onset, and onset symptoms on time to and age at Expanded Disability Status Scale (EDSS) 6.0 in patients with PPMS.
Of 5,779 patients with definite MS, 552 (10%) had PPMS. Median time to EDSS 6.0 was 14.0 years (95% confidence interval [CI] 11.3-16.7), reached at a median age of 58.6 years (95% CI 56.8-60.3). Sensory onset symptoms were associated with a longer time to and an older age at EDSS 6.0 (multivariable hazard ratios 0.55 [95% CI 0.35-0.87] and 0.54 [0.35-0.85]). Younger age at disease onset was associated with a longer time to but a younger age at EDSS 6.0. Gender and other onset symptoms were not associated with these outcomes. Fifty patients with PPMS (9%) fulfilled criteria for benign MS (EDSS < or =3.0 after 10 years' disease duration).
We identified 2 predictors of a slower disease progression in primary progressive multiple sclerosis. Sensory onset symptoms were associated with both a longer time to and a higher age at Expanded Disability Status Scale (EDSS) 6.0. A younger age at disease onset was associated with a longer time to EDSS 6.0, but patients with an early disease onset reached EDSS 6.0 at a younger age.
Neurology 12/2009; 73(23):1996-2002. · 8.31 Impact Factor
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Expert Review of Neurotherapeutics 09/2009; 9(9):1263-5.
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Menopause 12/2007; · 3.76 Impact Factor
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Menopause 15(1):203; author reply 203-4. · 3.76 Impact Factor
