ObjectiveTo develop a valid algorithm for identifying multiple sclerosis (MS) cases in administrative health claims (AHC) datasets.MethodsWe used 4 AHC datasets from the Veterans Administration (VA), Kaiser Permanente Southern California (KPSC), Manitoba (Canada), and Saskatchewan (Canada). In the VA, KPSC, and Manitoba, we tested the performance of candidate algorithms based on inpatient, outpatient, and disease-modifying therapy (DMT) claims compared to medical records review using sensitivity, specificity, positive and negative predictive values, and interrater reliability (Youden J statistic) both overall and stratified by sex and age. In Saskatchewan, we tested the algorithms in a cohort randomly selected from the general population.ResultsThe preferred algorithm required ≥3 MS-related claims from any combination of inpatient, outpatient, or DMT claims within a 1-year time period; a 2-year time period provided little gain in performance. Algorithms including DMT claims performed better than those that did not. Sensitivity (86.6%–96.0%), specificity (66.7%–99.0%), positive predictive value (95.4%–99.0%), and interrater reliability (Youden J = 0.60–0.92) were generally stable across datasets and across strata. Some variation in performance in the stratified analyses was observed but largely reflected changes in the composition of the strata. In Saskatchewan, the preferred algorithm had a sensitivity of 96%, specificity of 99%, positive predictive value of 99%, and negative predictive value of 96%.ConclusionsThe performance of each algorithm was remarkably consistent across datasets. The preferred algorithm required ≥3 MS-related claims from any combination of inpatient, outpatient, or DMT use within 1 year. We recommend this algorithm as the standard AHC case definition for MS.

Objective To determine the safety of direct oral anticoagulant (DOAC) use compared with warfarin use for the treatment of venous thromboembolism. Design Retrospective matched cohort study conducted between 1 January 2009 and 31 March 2016. Setting Community based, using healthcare data from six jurisdictions in Canada and the United States. Participants 59 525 adults (12 489 DOAC users; 47 036 warfarin users) with a new diagnosis of venous thromboembolism and a prescription for a DOAC or warfarin within 30 days of diagnosis. Main outcome measures Outcomes included hospital admission or emergency department visit for major bleeding and all cause mortality within 90 days after starting treatment. Propensity score matching and shared frailty models were used to estimate adjusted hazard ratios of the outcomes comparing DOACs with warfarin. Analyses were conducted independently at each site, with meta-analytical methods used to estimate pooled hazard ratios across sites. Results Of the 59 525 participants, 1967 (3.3%) had a major bleed and 1029 (1.7%) died over a mean follow-up of 85.2 days. The risk of major bleeding was similar for DOAC compared with warfarin use (pooled hazard ratio 0.92, 95% confidence interval 0.82 to 1.03), with the overall direction of the association favouring DOAC use. No difference was found in the risk of death (pooled hazard ratio 0.99, 0.84 to 1.16) for DOACs compared with warfarin use. There was no evidence of heterogeneity across centres, between patients with and without chronic kidney disease, across age groups, or between male and female patients. Conclusions In this analysis of adults with incident venous thromboembolism, treatment with DOACs, compared with warfarin, was not associated with an increased risk of major bleeding or all cause mortality in the first 90 days of treatment. Trial registration Clinical trials NCT02833987.

Background: Relatively little is known about the use of disease-modifying drugs (DMDs) for multiple sclerosis (MS) in the population-based universal healthcare setting. This study aimed to describe the characteristics of a population-based cohort with MS and their DMD exposure in four Canadian provinces.Methods: We identified all adults (aged ≥18 years) with MS using linked population-based health administrative data. Individuals were followed from the most recent of their first MS or demyelinating event or 01/January/1996(study entry), to the earliest of death, emigration, or 31/March/2018(study end). Cohort characteristics examined included sex, age, socioeconomic status, and comorbidity burden.Results: Overall, 10,418/35,894 (29%) of MS cases filled a DMD prescription during the 22-year study period. Most were women (n=7,683/10,418;74%), and 17% (n=1,745/10,418) had some comorbidity (Charlson Comorbidity Index≥1) at study entry. Nearly 20% (n=1,745/10,418) were aged ≥50 when filling their first DMD; the mean age was 39.6 years.Conclusions: Almost 1 in 6 people with MS had at least some comorbidity, and nearly 1 in 6 were ≥50 years old at the time of their first DMD. As these individuals are typically excluded from clinical trials, findings illustrate the need to understand the harms and benefits of DMD use in these understudied groups.

Background: Drug discontinuation (i.e., nonpersistence) is often attributed to the emergence of adverse effects. However, it is not known whether other factors increase the risk of nonpersistence when adverse effects occur. Objectives: To identify factors associated with early nonpersistence among patients experiencing adverse effects from newly prescribed medications. Methods: A questionnaire was mailed to new users of antihypertensive, antihyperglycemic, and lipid-lowering medications in Saskatchewan, Canada, between 2019 and 2020. Only respondents experiencing adverse effects were included. Responses were compared between the nonpersistent group (i.e., people who had discontinued their medication) and the persistent group (i.e., those who were taking their medication at the time of the survey). Statistically significant factors were tested in multivariable logistic regression models. Odds ratios (ORs) and 95% CIs were reported. Results: Of the 3973 returned questionnaires, 813 respondents experienced adverse -effects from their new medication and were included in the study. Of these, 143 respondents (17.5%) had stopped their medication at the time of survey completion; most discontinuations (72.1%) occurred within 1 month of the first dose. Nonpersistent patients were older, had lower income, and were less likely to be taking an antihyperglycemic medication. After covariate adjustment, 6 factors were independently associated with nonpersistence: age less than 65 years (OR 1.56 [95% CI 1.01e2.41]), female sex (1.67 [1.08 e2.59]), health condition not considered dangerous (2.09 [1.25e3.51]), medication not considered important for health (6.90 [4.40e10.84]), failure to expect adverse effects before starting medication (2.67 [1.74e4.10]), and taking 2 or more medications (0.45 [0.27e0.73]). Conclusion: Despite the strong link between the emergence of adverse effects and early nonpersistence, our findings confirm that this association is highly influenced by several factors external to the physical experiences caused by the new medication.