COVID-19 diagnostic testing and vaccinations among First Nations in Manitoba: A nations-based retrospective cohort study using linked administrative data, 2020-2021.

BACKGROUND: Differential access to healthcare has contributed to a higher burden of illness and mortality among First Nations compared to other people in Canada. Throughout the Coronavirus Disease 2019 (COVID-19) pandemic, First Nations organizations in Manitoba partnered with public health and Manitoba government officials to ensure First Nations had early, equitable and culturally safe access to COVID-19 diagnostic testing and vaccination. In this study, we examined whether prioritizing First Nations for vaccination was associated with faster uptake of COVID-19 vaccines among First Nations versus All Other Manitobans (AOM). METHODS AND FINDINGS: In this retrospective cohort study, we used linked, whole-population administrative data from the Manitoba healthcare system (February 2020 to December 2021) to determine rates of COVID-19 diagnostic testing, infection, and vaccination, and used adjusted restricted mean survival time (RMST) models to test whether First Nations received their first and second vaccine doses more quickly than other Manitobans. The cohort comprised 114,816 First Nations (50.6% female) and 1,262,760 AOM (50.1% female). First Nations were younger (72.3% were age 0 to 39 years) compared to AOM (51% were age 0 to 39 years) and were overrepresented in the lowest 2 income quintiles (81.6% versus 35.6% for AOM). The 2 groups had a similar burden of comorbidities (65.8% of First Nations had none and 6.3% had 3 or more; 65.9% of AOM had none and 6.0% had 3 or more) and existing mental disorders (36.9% of First Nations were diagnosed with a mood/anxiety disorder, psychosis, personality disorder, or substance use disorder versus 35.2% of AOM). First Nations had crude infection rates of up to 17.20 (95% CI 17.15 to 17.24) COVID-19 infections/1,000 person-months compared with up to 6.24 (95% CI 6.16 to 6.32) infections/1,000 person-months among AOM. First Nations had crude diagnostic testing rates of up to 103.19 (95% CI 103.06 to 103.32) diagnostic COVID-19 tests/1,000 person-months compared with up to 61.52 (95% CI 61.47 to 61.57) tests/1,000 person-months among AOM. Prioritizing First Nations to receive vaccines was associated with faster vaccine uptake among First Nations versus other Manitobans. After adjusting for age, sex, income, region of residence, mental health conditions, and comorbidities, we found that First Nations residents received their first vaccine dose an average of 15.5 (95% CI 14.9 to 16.0) days sooner and their second dose 13.9 (95% CI 13.3 to 14.5) days sooner than other Manitobans in the same age group. The study was limited by the discontinuation of population-based COVID-19 testing and data collection in December 2021. As well, it would have been valuable to have contextual data on potential barriers to COVID-19 testing or vaccination, including, for example, information on social and structural barriers faced by Indigenous and other racialized people, or the distrust Indigenous people may have in governments due to historical harms. CONCLUSION: In this study, we observed that the partnered COVID-19 response between First Nations and the Manitoba government, which oversaw creation and enactment of policies prioritizing First Nations for vaccines, was associated with vaccine acceptance and quick uptake among First Nations. This approach may serve as a useful framework for future public health efforts in Manitoba and other jurisdictions across Canada.

Adverse Events Associated With Disease-Modifying Drugs for Multiple Sclerosis: A Multiregional Population-Based Study

BACKGROUND AND OBJECTIVES: It is not possible to fully establish the safety of a disease-modifying drug (DMD) for multiple sclerosis (MS) from randomized controlled trials as only very common adverse events occurring over the short-term can be captured, and the quality of reporting has been variable. We examined the relationship between the DMDs for MS and potential adverse events in a multiregion population-based study. METHODS: We identified people with MS using linked administrative health data from 4 Canadian provinces. MS cases were followed from the most recent of first MS or related demyelinating disease event on January 1, 1996, until the earliest of emigration, death, or December 31, 2017. DMD exposure primarily comprised ß-interferon, glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate, teriflunomide, and alemtuzumab. We examined associations between DMD exposure and infection-related hospitalizations and physician visits using recurrent events proportional means models and between DMD exposure and 15 broad categories of incident adverse events using stratified multivariate Cox proportional hazard models. RESULTS: We identified 35,894 people with MS. While virtually all DMDs were associated with a 42%-61% lower risk of infection-related hospitalizations, there was a modest increase in infection-related physician visits by 10%-33% for select DMDs. For incident adverse events, most elevated risks involved a second-generation DMD, with alemtuzumab's hazard of thyroid disorders being 19.42 (95% CI 9.29-36.51), hypertension 4.96 (95% CI 1.78-13.84), and cardiovascular disease 3.72 (95% CI 2.12-6.53). Natalizumab's highest risk was for cardiovascular disease (adjusted hazard ratio [aHR] 1.61; 95% CI 1.24-2.10). For the oral DMDs, fingolimod was associated with higher hazards of cerebrovascular (aHR 2.04; 95% CI 1.27-3.30) and ischemic heart diseases (aHR 1.64; 95% CI 1.10-2.44) and hypertension (aHR 1.73; 95% CI 1.30-2.31); teriflunomide with higher hazards of thyroid disorders (aHR 2.30; 95% CI 1.11-4.74), chronic liver disease (aHR 1.94; 95% CI 1.19-3.18), hypertension (aHR 1.76; 95% CI 1.32-2.37), and hyperlipidemia (aHR 1.61; 95% CI 1.07-2.44); and from complementary analyses (in 1 province), dimethyl fumarate with acute liver injury (aHR 6.55; 95% CI 1.96-21.87). DISCUSSION: Our study provides an extensive safety profile of several different DMDs used to treat MS in the real-world setting. Our findings not only complement those observed in short-term clinical trials but also provide new insights that help inform the risk-benefit profile of the DMDs used to treat MS in clinical practice. The results of this study highlight the continued need for long-term, independent safety studies of the DMDs used to treat MS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with MS, while DMD exposure reduces the risk of infection-related hospitalizations, there are increased risks of infection-related physician visits and incident adverse events for select DMDs.

Switching to second line MS disease-modifying therapies is associated with decreased relapse rate.

Background and objectives: While randomized, controlled trials (RCTs) are the gold standard for determining treatment efficacy, they do not capture the effectiveness of treatment during real-world use. We aimed to evaluate the association between demographics and multiple sclerosis (MS) disease-modifying therapy (DMT) exposure, including treatment adherence and switches between different DMTs, on the risk of subsequent MS relapse. Methods: All persons with relapsing-onset MS (pwRMS) living in Manitoba between 1999 and 2014 were identified from provincial healthcare databases using a validated case definition. Use of DMTs was abstracted from the provincial drug database covering all residents of Manitoba, including use of any DMT, stopping/starting any DMT, switches between different DMTs and adherence as defined by cumulative medication possession ratios (CUMMPRs) of 50, 70, 80 and 90%. Time to first-treated relapse was used as the outcome of interest in logistic regression and Cox-proportional hazards regression models adjusting for demographic covariates including age and year of diagnosis, sex, socioeconomic status and number of medical comorbidities. Results: 1780 pwRMS were identified, including 1,510 who were on DMT at some point in the study period. While total DMT exposure was not associated with the time to subsequent treated relapse, individuals who switched between more than 2 DMTs had higher post-switch rates of relapse. Switching to second-line DMTs was associated with a longer time to treated relapse in comparison to those who remained on a first-line DMT (HR 0.44; 95%CI: 0.32-0.62, p < 0.0001). Discussion: Switching to high-efficacy DMTs reduces the rates of subsequent MS relapse at the population level.

Do Patterns of Early Disease Severity Predict Grade 12 Academic Achievement in Youths With Childhood-Onset Chronic Rheumatic Diseases?

OBJECTIVE: To test the association of early disease severity with grade 12 standards test performance in individuals with childhood-onset chronic rheumatic diseases (ChildCRDs), including juvenile arthritis and systemic autoimmune rheumatic diseases. METHODS: We used linked provincial administrative data to identify patients with ChildCRDs born between 1979 and 1998 in Manitoba, Canada. Primary outcomes were Language and Arts Achievement Index (LAI) scores and Math Achievement Index (MAI) scores from grade 12 standards test results as well as enrollment data. The secondary outcome was enrollment in grade 12 by 17 years of age. Latent class trajectory analysis identified disease severity groups using physician visits following diagnosis. Multivariable linear regression tested the association of disease severity groups with LAI and MAI scores, and logistic regression tested the association of disease severity with age-appropriate enrollment, after adjusting for sociodemographic factors and psychiatric morbidities. RESULTS: The study cohort included 541 patients, 70.1% of whom were female. A 3-class trajectory model provided the best fit; it classified 9.7% of patients as having severe disease, 54.5% as having moderate disease, and 35.8% as having mild disease. After covariate adjustment, severe disease was associated with poorer LAI and MAI scores but not with age-appropriate enrollment. CONCLUSION: Among patients with ChildCRDs, those with severe disease performed more poorly on grade 12 standards tests, independent of sociodemographic and psychiatric risk factors. Clinicians should work with educators and policy makers to advocate for supports to improve educational outcomes of patients with ChildCRDs.

Disease-Modifying Drugs for Multiple Sclerosis and Association With Survival.

BACKGROUND AND OBJECTIVES: We examined the association between the disease-modifying drugs (DMDs) for multiple sclerosis (MS) and survival in a multiregion population-based study. METHODS: We accessed multiple administrative health databases from 4 Canadian provinces. Persons with MS were identified and followed from the most recent of the first MS or demyelinating event or January 1, 1996 (index date), until death, emigration, or December 31, 2017. Association between the first-generation and second-generation DMDs and all-cause mortality was examined using stratified Cox proportional hazard models, reported as adjusted hazard ratios (aHRs). Timing of DMD initiation was explored, with findings reported at 2, 5, or 10 years postindex date, representing very early, early, or late initiation. RESULTS: We identified 35,894 persons with MS; 72% were female. The mean age at index date was 44.5 years (SD = 13.6). The total person-years of follow-up while DMD-exposed was 89,180, and total person-years while unexposed was 342,217. Compared with no exposure, exposure to any DMD or to any first-generation DMD was associated with a 26% lower hazard of mortality (both aHRs 0.74; 95% CI 0.56-0.98), while any second-generation DMD exposure was associated with a 33% lower hazard (aHR 0.67; 95% CI 0.46-0.98). Earlier DMD initiation (beta-interferon or glatiramer acetate vs no exposure) was associated with a significant mortality effect (p < 0.05), while later initiation was not (95% CIs included 1). However, the survival advantage with earlier initiation diminished over time, no longer reaching statistical significance at 15 years postindex date. DISCUSSION: Our study demonstrates an association between the DMDs for MS and improved survival in the real-world setting.

Incidence and Predictors of Suicide Attempts and Suicide Deaths Among Individuals Recently Hospitalized for a Mental Disorder: A Population-Based Study.

Objective: To examine the incidence and predictors of suicide attempts and deaths in the year after psychiatric hospitalization.Methods: A population-based dataset was used to develop a cohort of individuals 18 years or older admitted with a mental disorder (defined by ICD-10 codes) from 2005 to 2016 (n = 26,975) in Manitoba, Canada. Using Cox regression, hazard ratios were calculated for each covariate among those who attempted and died by suicide in the year following hospitalization, while adjusting for confounders.Results: In the year following hospitalization for a mental disorder, 0.7% of the individuals died by suicide and 3.5% attempted suicide. Statistically significant risk factors for suicide in the year after discharge from psychiatric hospitalization included male sex (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.10-1.97) and urban location (HR, 1.37; 95% CI, 1.02-1.85) and for attempting suicide included female sex (HR, 0.63; 95% CI, 0.55-0.72), living rurally (HR, 0.66; 95% CI, 0.58-0.75), a previous mental disorder (HR, 1.63; 95% CI, 1.38-1.92), justice involvement (HR, 1.48; 95% CI, 1.28-1.70), and being on income assistance (HR, 1.17; 95% CI, 1.01-1.35) (P < .05 for all). Age (HR, 0.99; 95% CI, 0.99-0.99) (P < .05) was associated with a reduced rate of suicide attempts.Conclusions: Further research into interventions to address the identified risk factors for suicide in the recently discharged population is critical to improve management.

Cardiovascular disease and the risk of dementia: a survival analysis using administrative data from Manitoba.

OBJECTIVES: Recent research has shown that cardiovascular disease (CVD) raises the risk of dementia and other forms of cognitive decline. Generally, these studies are unable to model the time of diagnosis of CVD in their analyses and treat CVD as a time-fixed variable. Our objective was to assess the risk of being diagnosed with dementia for individuals diagnosed with CVD when CVD is time-dependent. METHODS: We performed a retrospective cohort study using administrative health datasets from the Manitoba Population Research Data Repository in Canada. We constructed a longitudinal dataset to track individuals enrolled in the Manitoba Health Insurance Registry between April 1, 1997 and March 31, 2015. The study population consisted of 496,192 individuals 30 years of age or older who were not diagnosed with CVD or dementia prior to April 1, 1997. Diagnoses of CVD and dementia were based on diagnosis codes from medical claims and hospitalizations and the use of prescription medications. Hazard ratios were then computed using adjusted Cox-proportional hazards analyses. RESULTS: Among the CVD subgroups considered, atrial fibrillation, ischemic heart disease, and stroke increased the risk of developing dementia, with stroke doubling one's risk of being diagnosed with the disease (hazard ratio: 1.95; 95% confidence interval: 1.9, 2.01). Age, lower socioeconomic status, and worsening comorbidities also increased the risk of being diagnosed with dementia. CONCLUSION: A diagnosis of CVD is associated with an increased risk of a future diagnosis of dementia. Promoting good cardiovascular health may serve as an effective measure for preventing dementia.

RéSUMé: OBJECTIFS: De récentes études montrent que la maladie cardiovasculaire (MCV) accroît le risque de démence et d'autres formes de déclin cognitif. De façon générale, ces études sont incapables de modéliser la date d'un diagnostic de MCV dans leurs analyses et traitent donc les MCV comme des variables fixes dans le temps. Nous avons cherché à évaluer le risque de recevoir un diagnostic de démence chez les personnes ayant un diagnostic de MCV quand la MCV est variable dans le temps. MéTHODE: Nous avons mené une étude de cohorte rétrospective à l'aide des fichiers de données administratives sur la santé du Dépôt de données de recherche en santé des populations du Manitoba, au Canada. Nous avons construit un fichier longitudinal pour suivre les personnes inscrites au registre d'assurance-maladie du Manitoba entre le 1er avril 1997 et le 31 mars 2015. La population étudiée comptait 496 192 personnes de 30 ans et plus n'ayant pas reçu de diagnostic de MCV ou de démence avant le 1er avril 1997. Les diagnostics de MCV et de démence étaient fondés sur les codes diagnostiques dans les demandes d'indemnisation de frais médicaux et les dossiers d'hospitalisation, et sur l'utilisation de médicaments sur ordonnance. Les indices de risque ont été calculés à l'aide du modèle à risques proportionnels de Cox. RéSULTATS: Dans les sous-groupes atteints de MCV que nous avons étudiés, la fibrillation atriale, la cardiopathie ischémique et l'AVC faisaient augmenter le risque de démence; l'AVC, en particulier, doublait le risque d'être diagnostiqué avec cette maladie (indice de risque : 1,95; intervalle de confiance de 95% : 1,9, 2,01). L'âge, le faible statut socioéconomique et l'évolution défavorable des comorbidités faisaient aussi augmenter le risque de recevoir un diagnostic de démence. CONCLUSION: Un diagnostic de MCV est associé à un risque accru de diagnostic de démence plus tard. La promotion d'une bonne santé cardiovasculaire pourrait donc être un moyen efficace de prévenir la démence.

Development of an indicator of smoking status for people with multiple sclerosis in administrative data.

BACKGROUND: Administrative data lack health behavior information. METHODS: We developed an administrative case definition for past or current ('ever smoking') in 1320 individuals with MS from Manitoba, Canada. Candidate indicators for 'ever smoked' included smoking cessation medications, and diagnosis codes for tobacco use and chronic obstructive pulmonary disease, using variable lookback periods. RESULTS: When compared to self-reported smoking status, the case definition incorporating all indicators over a lifetime lookback period had a sensitivity of 31.98%, and positive predictive value of 78.26%. CONCLUSION: This smoking status definition could only partially control for confounding due to smoking because of the low sensitivity.

Association of alcohol use disorder on alcohol-related cancers, diabetes, ischemic heart disease and death: a population-based, matched cohort study.

BACKGROUND AND AIMS: High-risk alcohol consumption is associated with compromised health. This study aimed to compare the incidence of alcohol-related cancers, diabetes, ischemic heart disease (IHD) and mortality between those with and without an indication of alcohol use disorder (AUD). DESIGN: Retrospective, population-based, matched cohort study using data from the Manitoba Population Research Data Repository. Rates were modeled using generalized linear models with either negative binomial distribution or Poisson distribution and a log offset of person-years to account for each person's time to follow-up. SETTING: Manitoba, Canada. PARTICIPANTS: Individuals aged ≥ 12 years with a first indication of AUD (index date) between 1 April 1990 and 31 March 2015 were matched to five controls based on age, sex and geographical region at index. This study included 53 410 individuals with AUD and 264 857 matched controls. MEASUREMENTS: Adjusted rate ratios (aRR) and 95% confidence intervals (CI) were determined for each outcome from 5 years prior to and 20 years after AUD detection. FINDINGS: Alcohol-related cancers (aRR = 4.85, 95% CI = 3.88-6.07 and aRR = 1.85, 95% CI = 1.35-2.53 for men and women, respectively), diabetes (aRR = 1.74, 95% CI = 1.50-2.02 and aRR = 2.43, 95% CI = 2.20-2.68) and IHD (aRR = 3.59, 95% CI = 3.31-3.90 and aRR = 2.92, 95% CI = 2.50-3.41) peaked in the 1 year prior to index for those with AUD compared with matched controls. All-cause mortality (aRR = 3.31, 95% CI = 3.09-3.55 and aRR =3.61, 95% CI = 3.21-4.04) was highest in the year of index and remained higher among cases compared with controls throughout the 20-year follow-up. CONCLUSION: People with alcohol use disorder appear to have higher rates of adverse health outcomes in the year before alcohol use disorder recognition, and death at the time of alcohol use disorder recognition, compared with matched controls.

Suicidal Risk and Adverse Social Outcomes in Adulthood Associated with Child and Adolescent Mental Disorders.

OBJECTIVE: The life course of children and adolescents with mental disorders is an important area of investigation, yet it remains understudied. This study provides a first-ever comprehensive examination of the relationship between child and adolescent mental disorders and subsequent suicidal and adverse social outcomes in early adulthood using population-based data. METHODS: De-identified administrative databases were used to create a birth cohort of 60,838 residents of Manitoba born between April 1980 to March 1985 who were followed until March 2015. Unadjusted and adjusted hazard ratios (aHRs) and odds ratios (aORs) were calculated to determine associations between physician-diagnosed mental disorders in childhood or adolescence and a range of adverse early adulthood (ages 18 to 35) outcomes. RESULTS: Diagnoses of mood/anxiety disorders, attention-deficit hyperactivity disorder, substance use disorder, conduct disorder, psychotic disorder, personality disorders in childhood or adolescence were associated with having the same diagnoses in adulthood. These mental disorder diagnoses in childhood/adolescence were strongly associated with an increased risk of suicidal behaviors and adverse adult social outcomes in adulthood. Similarly, suicide attempts in adolescence conferred an increased risk in adulthood of suicide death (aHR: 3.6; 95% confidence interval [CI]: 1.9-6.9), suicide attempts (aHR: 6.2; CI: 5.0-7.6), social housing use (aHR: 1.7; CI 1.4-2.1), income assistance (aHR: 1.8; CI 1.6-2.1), criminal accusation (aHR: 2.2; CI 2.0-2.5), criminal victimization (aHR:2.5; CI 2.2-2.7), and not completing high school (aOR: 3.1; CI: 2.5-3.9). CONCLUSION: Mental disorders diagnosed in childhood and adolescence are important risk factors not only for mental disorders in adulthood but also for a range of early adult adversity. These findings provide an evidence-based prognosis of children's long-term well-being and a rationale for ensuring timely access to mental health services. Better population-level mental health promotion and early intervention for children and adolescents with mental disorders are promising for improving future adult outcomes.

Disease-modifying drugs for multiple sclerosis and subsequent health service use.

OBJECTIVE: We assessed the relationship between the multiple sclerosis (MS) disease-modifying drugs (DMDs) and healthcare use. METHODS: Persons with MS (aged ⩾18 years) were identified using linked population-based health administrative data in four Canadian provinces and were followed from the most recent of their first MS/demyelinating event or 1 January 1996 until the earliest of death, emigration, or study end (31 December 2017 or 31 March 2018). Prescription records captured DMD exposure, examined as any DMD, then by generation (first-generation (the injectables) or second-generation (orals/infusions)) and individual DMD. The associations with subsequent all-cause hospitalizations and physician visits were examined using proportional means model and negative binomial regression. RESULTS: Of 35,894 MS cases (72% female), mean follow-up was 12.0 years, with person-years of DMD exposure for any, or any first- or second-generation DMD being 63,290, 54,605 and 8685, respectively. Any DMD or any first-generation DMD exposure (versus non-exposure) was associated with a 24% lower hazard of hospitalization (adjusted hazard ratio, aHR: 0.76; 95% confidence intervals (CIs): 0.71-0.82), rising to 29% for the second-generation DMDs (aHR: 0.71; 95% CI: 0.58-0.88). This ranged from 18% for teriflunomide (aHR: 0.82; 95% CI: 0.67-1.00) to 44% for fingolimod (aHR: 0.56; 95% CI: 0.36-0.87). In contrast, DMD exposure was generally not associated with substantial differences in physician visits. CONCLUSION: Findings provide real-world evidence of a beneficial relationship between DMD exposure and hospitalizations.

Development and Internal Validation of a Disability Algorithm for Multiple Sclerosis in Administrative Data.

Objective: We developed and internally validated an algorithm for disability status in multiple sclerosis (MS) using administrative data. Methods: We linked administrative data from Manitoba, Canada to a clinical dataset with Expanded Disability Status Scale (EDSS) scores for people with MS. Clinical EDSS scores constituted the reference standard. We created candidate indicators using the administrative data. These included indicators based on use of particular health care services (home care, long-term care, rehabilitation admission), use of specific diagnostic codes (such as spasticity, quadriplegia), and codes based on use of Employment and Income Insurance. We developed algorithms to predict severe disability (EDSS ≥6.0), and to predict disability as a continuous measure. We manually developed algorithms, and also employed regression approaches. After we selected our preferred algorithms for disability, we tested their association with health care use due to any cause and infection after potential confounders. Results: We linked clinical and administrative data for 1,767 persons with MS, most of whom were women living in urban areas. All individual indicators tested had specificities >90% for severe disability, and all but a diagnosis of visual disturbance had positive predictive values (PPV) >70%. The combination of home care or long-term care use or rehabilitation admission had a sensitivity of 61.9%, specificity of 90.76%, PPV of 70.06% and negative predictive of 87.21%. Based on regression modeling, the best-performing algorithm for predicting the EDSS as a continuous variable included age, home care use, long-term care admission, admission for rehabilitation, visual disturbance, other paralytic syndromes and spasticity. The mean difference between observed and predicted values of the EDSS was -0.0644 (95%CI -0.1632, 0.0304). Greater disability, whether measured using the clinical EDSS or either of the administrative data algorithms was similarly associated with increased hospitalization rates due to any cause and infection. Conclusion: We developed and internally validated an algorithm for disability in MS using administrative data that may support population-based studies that wish to account for disability status but do not have access to clinical data sources with this information. We also found that more severe disability is associated with increased health care use, including due to infection.

Colorectal Cancer Survival in Multiple Sclerosis: A Matched Cohort Study.

BACKGROUND AND OBJECTIVES: We tested the hypothesis that overall and cancer-specific survival following colorectal cancer diagnosis is lower in persons with multiple sclerosis (MS) than without MS, using a retrospective matched cohort design. METHODS: Using population-based administrative data in Manitoba and Ontario we identified persons with MS using a validated case definition, and linked these cohorts to cancer registries to identify those with colorectal cancer. We selected persons with colorectal cancer and without MS matching 4:1 on birth year, sex, cancer diagnosis year and region. We used Cox proportional hazards regression to compare all-cause survival between cohorts adjusting for age at cancer diagnosis, cancer diagnosis year, income, region, and Elixhauser comorbidity score. We compared cancer-specific survival between cohorts using a cause-specific hazards model. We pooled findings across provinces using random-effects meta-analysis. Complementary analyses using a subcohort from Ontario adjusted for cancer stage and disability status, as measured based on the use of home care or long-term care services. RESULTS: We included 338 MS cases and 1352 controls with colorectal cancer. The mean (SD) age at cancer diagnosis was 64.7 (11.1) years. After adjustment, MS was associated with an increased hazard for all-cause death which was highest six months post-diagnosis (hazard ratio [HR] 1.45; 95%CI: 1.19-1.76), then declined over time (HR [95%CI] 1 year: 1.34 [1.09-1.63], 2 years: 1.24 [0.99-1.56]; 5 years: 1.10 [0.80-1.50]). MS was associated with increased cancer-specific death at 6 months post-diagnosis only (HR 1.29; 95%CI: 1.04-1.61). After adjusting for cancer stage, MS was associated with an increased hazard of death due to any cause (1.60; 95%CI: 1.16, 2.21) and with cancer-specific death (HR 1.47; 95%CI: 1.02, 2.12). The association of MS and all cause death was partially attenuated after adjustment for disability status (HR 1.37; 95%CI: 0.97, 1.92), as was the association with cancer-specific death (HR 1.34; 95%CI: 0.91, 1.97). DISCUSSION: Overall and cancer-specific survival was lower in persons with than without MS in the early period following colorectal cancer diagnosis. Further study is warranted to determine what factors underlie these worse outcomes.

Use of pharmacotherapy for alcohol use disorder in Manitoba, Canada: A whole-population cohort study.

OBJECTIVE: Update the evidence on use of pharmacotherapy for alcohol use disorder in a Canadian population. METHODS: Using whole-population administrative data from Manitoba, Canada, we identified all residents age 12+ who were first diagnosed with alcohol use disorder between April 1, 1996 and March 31, 2015, and compared characteristics of those who filled a prescription for naltrexone, acamprosate or disulfiram at least once during that period to those who did not fill a prescription for an alcohol use disorder medication. RESULTS: Only 1.3% of individuals with alcohol use disorder received pharmacotherapy (62.3% of prescriptions were for naltrexone, 39.4% for acamprosate, 7.5% for disulfiram). Most prescriptions came from family physicians in urban alcohol use disorder (53.6%) and psychiatrists (22.3%). Individuals were more likely to fill a prescription for alcohol use disorder medication if they lived in an urban vs rural environment (OR 2.25; 95% CI 1.83-2.77) or had a mood/anxiety disorder diagnosis vs no diagnosis (OR 2.40, 95% CI 1.98-2.90) in the five years before being diagnosed with alcohol use disorder. CONCLUSION: Despite established evidence for the effectiveness of pharmacotherapy for alcohol use disorder, these medications continue to be profoundly underutilized in Canada.

Breast Cancer Survival in Multiple Sclerosis: A Matched Cohort Study.

OBJECTIVE: To test the hypotheses that overall survival and cancer-specific survival after breast cancer diagnosis would be lower in persons with multiple sclerosis (MS) as compared to persons without MS using a retrospective matched cohort design. METHODS: We applied a validated case definition to population-based administrative data in Manitoba and Ontario, Canada, to identify women with MS. We linked the MS cohorts to cancer registries to identify women with breast cancer. Then we selected 4 breast cancer controls without MS matched on birth year, cancer diagnosis year, and region. We compared all-cause survival between cohorts using Cox proportional hazards regression adjusting for age at cancer diagnosis, cancer diagnosis period, income quintile, region, and Elixhauser comorbidity score. We compared cancer-specific survival between cohorts using a multivariable cause-specific hazards model. We pooled findings between provinces using meta-analysis. RESULTS: We included 779 patients with MS and 3,116 controls with breast cancer. Most patients with stage data (1,976/2,822 [70.0%]) were diagnosed with stage I or II breast cancer and the mean (SD) age at diagnosis was 57.8 (10.7) years. After adjustment for covariates, MS was associated with a 28% increased hazard for all-cause mortality (hazard ratio [HR] 1.28; 95% confidence interval [CI] 1.08-1.53), but was not associated with altered cancer-specific survival (HR 0.98; 95% CI 0.65-1.46). CONCLUSION: Women with MS have lower all-cause survival after breast cancer diagnosis than women without MS. Future studies should confirm these findings in other populations and identify MS-specific factors associated with worse prognosis.

Characteristics of a population-based multiple sclerosis cohort treated with disease-modifying drugs in a universal healthcare setting.

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 1 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.

Cancer Incidence and Mortality Rates in Multiple Sclerosis: A Matched Cohort Study.

OBJECTIVE: To determine whether cancer risk differs in people with and without multiple sclerosis (MS), we compared incidence rates and cancer-specific mortality rates in MS and matched cohorts using population-based data sources. METHODS: We conducted a retrospective matched cohort study using population-based administrative data from Manitoba and Ontario, Canada. We applied a validated case definition to identify MS cases, then selected 5 controls without MS matched on birth year, sex, and region. We linked these cohorts to cancer registries, and estimated incidence of breast, colorectal, and 13 other cancers. For breast and colorectal cancers, we constructed Cox models adjusting for age at the index date, area-level socioeconomic status, region, birth cohort year, and comorbidity. We pooled findings across provinces using meta-analysis. RESULTS: We included 53,983 MS cases and 269,915 controls. Multivariable analyses showed no difference in breast cancer risk (pooled hazard ratio [HR] 0.92 [95% confidence interval (CI) 0.78-1.09]) or colorectal cancer risk (pooled HR 0.83 [95% CI 0.64-1.07]) between the cohorts. Mortality rates for breast and colorectal did not differ between cohorts. Bladder cancer incidence and mortality rates were higher among the MS cohort. Although the incidence of prostate, uterine, and CNS cancers differed between the MS and matched cohorts, mortality rates did not. CONCLUSION: The incidence of breast and colorectal cancers does not differ between persons with and without MS; however, the incidence of bladder cancer is increased. Reported differences in the incidence of some cancers in the MS population may reflect ascertainment differences rather than true differences.

Health service use among Manitobans with alcohol use disorder: a population-based matched cohort study.

BACKGROUND: Alcohol is the drug most commonly used by Canadians, with multiple impacts on health and health service use. We examined patterns of short- and long-term health service use among people with a diagnosis of alcohol use disorder. METHODS: In this retrospective matched cohort study, we used population-based administrative data from the province of Manitoba, Canada, to identify individuals aged 12 years or older with a first indication of alcohol use disorder (index date) in the period 1990 to 2015. We matched cases (those with diagnosis of alcohol use disorder) to controls (those without this diagnosis), at a 1:5 ratio, on the basis of age, sex, geographic region and income quintile at the index date. The outcome measures were inpatient hospital admission, outpatient physician visits, emergency department visits and use of prescription medications. We modelled crude rates using generalized estimating equations with either a negative binomial or a Poisson distribution RESULTS: We identified 53 410 people with alcohol use disorder and 264 857 matched controls. All outcomes occurred at a higher rate among people with the disorder than among controls. For example, during the year of diagnosis, the rate ratio for hospital admission was 4.0 (95% confidence interval [CI] 3.9-4.2) for women and 4.5 (95% CI 4.4-4.7) for men. All rates of health service use peaked close to the index date, but remained significantly higher among people with alcohol use disorder than among controls for 20 years. Among people with alcohol use disorder, the most commonly filled prescriptions were for psycholeptics, whereas among controls, the most commonly filled prescriptions were for sex hormones (women) and antihypertensives (men). INTERPRETATION: Compared with controls, people with alcohol use disorder used significantly more health services from the time of diagnosis and over the next 20 years. This finding highlights the need for better detection and early intervention to reduce the need for acute and emergency care, as well as the need for improved management of alcohol use disorder over the longer term.

Overlap between child protection services and the youth justice system: protocol for a retrospective population-based cohort study using linked administrative data in Manitoba, Canada.

INTRODUCTION: Children who have a history of involvement in child protection services (CPS) are over-represented in the youth and adult criminal justice systems. There are significant health and socioeconomic implications for individuals involved in either or both CPS and the justice system. Understanding the 'overlap' between these two systems would provide insight into the health and social needs of this population. This protocol describes a research programme on the relationship between the child welfare and the youth justice systems, looking specifically at the population involved in both CPS and the youth justice system. We will examine the characteristics associated with involvement in these systems, justice system trajectories of individuals with a history of CPS involvement and early adult outcomes of children involved in both systems. METHODS AND ANALYSIS: Administrative data sets will be linked at the individual level for three cohorts born 1991, 1994 and 1998 in Manitoba, Canada. Involvement in CPS will be categorised as 'placed in out-of-home care', 'received in-home services, but was not placed in care' or 'no involvement'. Involvement in the youth justice system will be examined through contacts with police between ages 12 and 17 that either led to charges or did not proceed. Individual, maternal and neighbourhood characteristics will be examined to identify individuals at greatest risk of involvement in one or both systems. ETHICS AND DISSEMINATION: The study was approved by the University of Manitoba Health Research Ethics Board and permission to access data sets has been granted by all data providers. We also received approval for the study from the First Nations Health and Social Secretariat of Manitoba's Health Information Research Governance Committee and the Manitoba Metis Federation. Strategies to disseminate study results will include engagement of stakeholders and policymakers through meetings and workshops, scientific publications and presentations, and social media.

The Intersection between Criminal Accusations, Victimization, and Mental Disorders: A Canadian Population-Based Study.

OBJECTIVE: Understand the relationship between criminal accusations, victimization, and mental disorders at a population level using administrative data from Manitoba, Canada. METHOD: Residents aged 18 to 64 between April 1, 2007, and March 31, 2012 (N = 793,024) with hospital- and physician-diagnosed mental disorders were compared to those without. Overall and per-person rates of criminal accusations and reported victimization in the 2011/2012 fiscal year were examined. Relative risks were calculated, adjusting for age, sex, income, and presence of a substance use disorder. The overlap between diagnosed mental disorders, accusations, and victimization with a χ2 test of independence was studied. RESULTS: Twenty-four percent (n = 188,693) of the population had a mental disorder over the 5-year time frame. Four to fifteen percent of those with a mental disorder had a criminal accusation, compared to 2.4% of the referent group. Individuals with mental disorders, especially psychotic or personality disorders, were often living in low-income, urban neighborhoods. The adjusted relative risk of accusations and victimization remained 2 to 5 times higher in those with mental disorders compared to the referent group. Criminal accusations and victimization were most prevalent among individuals with a history of attempted suicide (15.2% had an accusation and 8.1% were victims). The risk of victimization in the same year as a criminal accusation was significantly increased among those with mental disorders compared to those without (χ2 = 211.8, P < 0.001). CONCLUSIONS: Individuals with mental disorders are at elevated risk of both criminal involvement and victimization. The identification of these multiply-stigmatized individuals may lead to better intervention and support.