Xinya Lu

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.

Adherence and persistence to drug therapies for multiple sclerosis: A population-based study

OBJECTIVE We aimed to estimate the prevalence and predictors of optimal adherence and persistence to the disease-modifying therapies (DMT) for multiple sclerosis (MS) in 3 Canadian provinces. METHODS We used population-based administrative databases in British Columbia (BC), Saskatchewan, and Manitoba. All individuals receiving DMT (interferon-B-1b, interferon-B-1a, and glatiramer acetate) between 1-January-1996 and 31-December-2011 (BC), 31-March-2014 (Saskatchewan), or 31-March-2012 (Manitoba) were included. One-year adherence was estimated using the proportion of days covered (PDC). Persistence was defined as time to DMT discontinuation. Regression models were used to assess predictors of adherence and persistence; results were pooled using random effects meta-analysis. RESULTS 4830 individuals were included. When results were combined, an estimated 76.4% (95% CI: 69.1-82.4%) of subjects exhibited optimal adherence (PDC ≥80%). Median time to discontinuation of the initial DMT was 1.9 years (95% CI: 1.6-2.1) in Manitoba, 2.8 years (95% CI: 2.5-3.0) in BC, and 4.0 years (95% CI: 3.5-4.6) in Saskatchewan. Age, sex and socioeconomic status were not associated with adherence or persistence. Individuals who had ≥4 physician visits during the year prior to the first DMT dispensation were more likely to exhibit optimal adherence compared to those with fewer (0-3) physician visits. CONCLUSIONS We observed adherence that is higher than what has been reported for other chronic diseases, and other non-population-based MS cohorts. Closer examination as to why adherence appears to be relatively better in MS and how adherence influences disease outcomes could contribute to our understanding of MS, and prove useful in the management of other chronic diseases.

The Association Between Market Availability and Adherence to Antihypertensive Medications: An Observational Study

BACKGROUND High adherence to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reported in observational studies has frequently been attributed to improved tolerability. However, these agents are also relatively new to the market compared to other antihypertensive medications. We aimed to determine if an association exists between adherence and market availability of a specific antihypertensive agent. METHODS This retrospective cohort study used administrative data from Saskatchewan, Canada. Subjects were ≥40 years of age and received a new antihypertensive medication between 1994 and 2002. The primary outcome was the proportion of subjects achieving optimal adherence (≥80%) at 1 year, stratified by antihypertensive medication class and the year of availability. Adherence was measured using the cumulative mean gap ratio. RESULTS A total of 36,214 subjects met the inclusion criteria. Optimal adherence was observed in 4987 of 8623 (57.8%) subjects receiving ACEIs and 1013 of 1600 (63.3%) subjects receiving ARBs, but adherence appeared inconsistent when examined within each antihypertensive class. A pattern of increasing mean adherence was observed according to availability in the ACEI subgroup (Spearman r = 0.82; P = 0.007) but not the ARB subgroup (Spearman r = 0.41; P = 0.49). However, the association between availability and optimal adherence converged when ARB and ACEI users were combined (Spearman r = 0.85, P < 0.001). CONCLUSIONS Optimal adherence with ACEIs and ARBs compared to other antihypertensive agents may be associated with their relative availability. To what extent optimal adherence is also associated with improved tolerability, as currently believed, remains to be determined.

Adherence to disease‐modifying therapies for multiple sclerosis and subsequent hospitalizations

The aim of this study was to examine the association between optimal adherence to first‐line disease‐modifying therapies (DMT) for multiple sclerosis (MS) and hospitalizations.

Five years before multiple sclerosis onset: Phenotyping the prodrome:

Background: The multiple sclerosis (MS) prodrome is poorly characterized. Objective: To phenotype the MS prodrome via health care encounters. Methods: Using data from a population-based cohort study linking administrative and clinical data in four Canadian provinces, we compared physician and hospital encounters and prescriptions filled (via International Classification of Diseases chapters, physician specialty or drug classes) for MS subjects in the 5 years before the first demyelinating claim in an administrative cohort or the clinical symptom onset in an MS clinic-derived cohort, to age-, sex- and geographically matched controls. Rate ratios (RRs), 95% confidence intervals (95% CIs) and proportions were estimated. Results: The administrative and clinical cohorts included 13,951/66,940 and 3202/16,006 people with and without MS (cases/controls). Compared to controls, in the 5 years before the first demyelinating claim or symptom onset, cases had more physician and hospital encounters for the nervous (RR (range) = 2.31; 95% CI: 1.05–5.10 to 4.75; 95% CI: 3.11–7.25), sensory (RR (range) = 1.40; 95% CI: 1.34–1.46 to 2.28; 95% CI: 1.72–3.02), musculoskeletal (RR (range) = 1.19; 95% CI: 1.07–1.33 to 1.70; 95% CI: 1.57–1.85) and genito-urinary systems (RR (range) = 1.17; 95% CI: 1.05–1.30 to 1.59; 95% CI: 1.48–1.70). Cases had more psychiatrist and urologist encounters (RR (range) = 1.48; 95% CI: 1.36–1.62 to 1.80; 95% CI: 1.61–2.01), and higher proportions of musculoskeletal, genito-urinary or hormonal-related prescriptions (1.1–1.5 times higher, all p < 0.02). However, cases had fewer pregnancy-related encounters than controls (RR = 0.78; 95% CI: 0.71–0.86 to 0.88; 95% CI: 0.84–0.92). Conclusion: Phenotyping the prodrome 5 years before clinical recognition of MS is feasible.

Self-Monitoring Blood Glucose Test Strip Utilization in Saskatchewan: A Retrospective Study

OBJECTIVES To describe trends in blood glucose test strip (TS) utilization and cost in Saskatchewan. METHODS A retrospective analysis of TS use between January 1, 1996, and December 31, 2013, was conducted using population-based health administrative databases in Saskatchewan. The prescription drug database was used to describe the annual number of TS dispensations, the number of strips dispensed, the number of unique beneficiaries and the total costs. A patient-level analysis was also carried out to describe the patterns of TS use (i.e. light, moderate or heavy) by the entire cohort and by diabetes treatments. Potential cost savings due to a newly implemented restriction policy were estimated based on the most recent data (2013). RESULTS TS utilization increased dramatically between 1996 and 2013 in terms of the number of users and the average number of TSs received. The percentage of TS users receiving fewer than 4 TSs per week (i.e. light users) decreased by 20%, while the percentage of heavy users (i.e. those receiving more than 8 TSs per week) increased by 19%. During the same period, the use of high-risk oral hypoglycemic medications declined by 30% among all TS users. Heavy TS use was observed in at least one-third of all users, irrespective of treatment type. CONCLUSIONS If Saskatchewans newly imposed coverage limits had been applied in 2013, the costs of strips exceeding those limits would have totalled

Trends in Prevalence, Incidence and Pharmacologic Management of Diabetes Mellitus Among Seniors Newly Admitted to Long-Term Care Facilities in Saskatchewan between 2003 and 2011

2.5 million. Although TS use aligns with chronic disease care paradigms, the substantial costs and lack of evidence of patient outcomes demand better strategies to help reduce unnecessary use.Objectives: To describe trends in blood glucose test strip (TS) utilization and cost in Saskatchewan. Methods: A retrospective analysis of TS use between January 1, 1996, and December 31, 2013, was conducted using population-based health administrative databases in Saskatchewan. The prescription drug database was used to describe the annual number of TS dispensations, the number of strips dispensed, the number of unique beneficiaries and the total costs. A patient-level analysis was also carried out to describe the patterns of TS use (i.e. light, moderate or heavy) by the entire cohort and by diabetes treatments. Potential cost savings due to a newly implemented restriction policy were estimated based on the most recent data (2013). Results: TS utilization increased dramatically between 1996 and 2013 in terms of the number of users and the average number of TSs received. The percentage of TS users receiving fewer than 4 TSs per week (i.e. light users) decreased by 20%, while the percentage of heavy users (i.e. those receiving more than 8 TSs per week) increased by 19%. During the same period, the use of high-risk oral hypoglycemic medications declined by 30% among all TS users. Heavy TS use was observed in at least one-third of all users, irrespective of treatment type. Conclusions: If Saskatchewan’s newly imposed coverage limits had been applied in 2013, the costs of strips exceeding those limits would have totalled

Use and Misuse of Ezetimibe: Analysis of Use and Cost in Saskatchewan, a Canadian Jurisdiction With Broad Access

2.5 million. Although TS use aligns with chronic disease care paradigms, the substantial costs and lack of evidence of patient outcomes demand better strategies to help reduce unnecessary use.