Socioeconomic, health-related, and primary care physician characteristics associated with adherence to seasonal influenza vaccination in Manitoba, Canada: A population-wide record-linkage cohort study.

OBJECTIVE: There is a lack of published evidence on factors associated with adherence (maintenance of cumulative vaccination) to seasonal influenza vaccination (SIV) in Manitoba, Canada. We sought to assess the associations. METHODS: A cohort study utilizing Manitoba administrative health databases. Participants received SIV in 2010/11 influenza season, remained registered Manitoba residents and received at least one SIV during the 2011/12‒2019/20 seasons. We dichotomized adherence into "more adherent" (6‒9 SIVs) and "less adherent" (1‒5 SIVs) and used multivariable adjusted generalized estimating equation logistic regression models to assess association between adherence and socioeconomic, health-related, and primary care physician (PCP) characteristics, stratified by age group (< 5, 5‒17, 18‒44, 45‒64, ≥ 65) and sex. Results are adjusted odds ratios with 95% confidence intervals. RESULTS: There were 152,493 participants. Males had lower odds of being more adherent except among ≥ 65-year-olds (1.03, 95% CI 1.01‒1.05). Compared with the lowest income quintile, those in higher income quintiles had higher odds of being more adherent. The odds mostly increased with increase in income quintile. Those with more contact with their PCP/hospitalization one year prior had higher odds of being more adherent. The odds increased with increased contact among those 18‒44, 45‒64 and ≥ 65 years old. Those who had PCP with more years of practice had higher odds of being more adherent. The odds increased as years of practice increased. These observations were mostly consistent irrespective of sex. CONCLUSION: Female gender, having higher income, having more contact with the health system, and having an experienced PCP may determine increased adherence to SIV in Manitoba. These findings require attention.

RéSUMé: OBJECTIF: Il y a un manque de données publiées sur les facteurs associés à l'adhésion vaccinale (le maintien de la vaccination cumulée) pour le vaccin contre la grippe saisonnière (VGS) au Manitoba (Canada). Nous avons cherché à évaluer ces associations. MéTHODE: Étude de cohorte utilisant les bases de données administratives sur la santé du Manitoba. Les participantes et les participants ont reçu le VGS durant la saison grippale 2010‒2011, ont continué d'être des résidents inscrits du Manitoba et ont reçu au moins un VGS au cours des saisons 2011‒2012 à 2019‒2020. Nous avons dichotomisé l'adhésion en « adhésion importante ¼ (6 à 9 VGS) et en « faible adhésion ¼ (1 à 5 VGS) et utilisé des modèles de régression logistique ajustés multivariés avec des équations d'estimation généralisées pour déterminer l'association entre l'adhésion et les caractéristiques liées au statut socioéconomique, à l'état de santé et au médecin de premier recours (MPR), stratifiées par groupe d'âge (< 5 ans, 5‒17 ans, 18‒44 ans, 45‒64 ans et ≥ 65 ans) et par sexe. Les résultats sont des rapports de cotes ajustés avec des intervalles de confiance de 95%. RéSULTATS: Il y a eu 152 493 personnes participantes. La probabilité d'une adhésion importante était inférieure chez les hommes, sauf chez les ≥ 65 ans (1,03, IC 95% 1,01‒1,05). La probabilité d'une adhésion importante était aussi plus élevée dans les quintiles de revenu supérieurs que dans le quintile de revenu inférieur. Cette probabilité augmentait principalement avec l'augmentation du quintile de revenu. Les personnes ayant eu plus de contacts avec leur MPR ou ayant été hospitalisées au cours de l'année antérieure étaient plus susceptibles d'afficher une adhésion importante. Cette probabilité augmentait avec l'augmentation des contacts dans les groupes d'âge de 18‒44 ans, de 45‒64 ans et de ≥ 65 ans. Les personnes dont le MPR exerçait depuis un grand nombre d'années étaient plus susceptibles d'afficher une adhésion importante. Cette probabilité augmentait avec le nombre d'années d'exercice. Ces observations étaient pour la plupart cohérentes quel que soit le sexe. CONCLUSION: Le sexe féminin, le revenu élevé, le fait d'avoir plus de contacts avec le système de santé et le fait d'avoir un MPR d'expérience peuvent déterminer l'adhésion accrue à la vaccination contre la grippe saisonnière au Manitoba. Ces constats méritent d'être pris en considération.

A population-based, province-wide, record-linkage interrupted time series analysis of impact of the universal seasonal influenza vaccination policy on seasonal influenza vaccine uptake among 5-64-year-olds in the province of Manitoba, Canada.

INTRODUCTION: Universal seasonal influenza vaccination policy (USIVP) was introduced in Manitoba, Canada in 2010. Its impact on seasonal influenza vaccine (SIV) uptake remains underexplored. METHODS: We used population-wide data from Manitoba to assess the impact of the USIVP on SIV uptake. The study covered twenty influenza seasons (2000/01-2019/20). We summarized SIV uptake for influenza seasons before and after the USIVP. Utilizing a single-group interrupted time series analysis and appropriately accounting for autocorrelation, we estimated absolute change and annual trend in SIV uptake percentages among 5-17-, 18-44-, and 45-64-year-olds across strata of certain population socioeconomic and health-related characteristics following the USIVP. RESULTS: Average SIV uptake percentage in all age groups was significantly higher after compared with before the USIVP. Following the USIVP, there was no significant absolute change in SIV uptake percentage among 18-44- and 45-64-year-olds overall; however, a significant decrease was observed among 18-44-year-old males in the higher income quintiles, across healthcare utilization, and in some regions of residence. A significant increase was observed among 5-17-year-olds in the lowest income quintiles, in Northern Manitoba, and among those with less healthcare utilization, and no chronic disease. Overall, there was mostly no significant annual trend in SIV uptake percentage among 18-44-year-olds, and while a significant upward and downward trend was observed among 5-17-year-olds and 45-64-year-olds, respectively, a significant downward trend was observed across all strata of population characteristics within all age groups in Northern Manitoba. CONCLUSIONS: The USIVP in Manitoba was followed by an absolute increase in SIV uptake percentage only in some socioeconomically disadvantaged subpopulations among 5-17-year-olds. While there was mostly an upward annual trend in SIV uptake percentage among 5-17-year-olds, a downward trend was observed among 45-64-year-olds and across all age groups and subpopulations in socioeconomically disadvantaged Northern Manitoba. These findings are novel for Manitoba and require investigation and public health attention.

Nirmatrelvir-Ritonavir and COVID-19 Mortality and Hospitalization Among Patients With Vulnerability to COVID-19 Complications.

Importance: Postmarket analysis of individuals who receive nirmatrelvir and ritonavir (Paxlovid [Pfizer]) is essential because they differ substantially from individuals included in published clinical trials. Objective: To examine the association of nirmatrelvir and ritonavir with prevention of death or admission to hospital in individuals with different risks of complications from COVID-19 infection. Design, Setting, and Participants: This is a cohort study of adult patients in British Columbia, Canada, between February 1, 2022, and February 3, 2023. Patients were eligible if they belonged to 1 of 4 higher-risk groups of individuals who received priority for COVID-19 vaccination. Two groups included clinically extremely vulnerable (CEV) people who were severely (CEV1) or moderately immunocompromised (CEV2). CEV3 individuals were not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19. A fourth expanded eligibility (EXEL) group was added to allow wider access to nirmatrelvir and ritonavir for certain other higher-risk individuals who were not in a CEV group, such as those older than 70 years who were unvaccinated. Exposures: Patients with COVID-19 who received nirmatrelvir and ritonavir were matched to patients in the same vulnerability group; who were of the same sex, age, and propensity score for nirmatrelvir and ritonavir treatment; and who were also infected within 1 month of the individual treated with nirmatrelvir and ritonavir. Main Outcomes and Measures: The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days. Results: There were 6866 individuals included in the study, of whom 3888 (56.6%) were female and whose median (IQR) age was 70 (57-80) years. Compared with unexposed controls, treatment with nirmatrelvir and ritonavir was associated with statistically significant relative reductions in the primary outcome in the CEV1 group (560 patients; risk difference [RD], -2.5%, 95% CI, -4.8% to -0.2%) and the CEV2 group (2628 patients; RD, -1.7%; 95% CI, -2.9% to -0.5%). In the CEV3 group, the RD was -1.3%, but the findings were not statistically significant (2100 patients; 95% CI, -2.8% to 0.1%). In the EXEL group, treatment was associated with higher risk of the outcome (RD, 1.0%), but the findings were not statistically significant (1578 patients; 95% CI, -0.9% to 2.9%). Conclusions and Relevance: In this cohort study of 6866 individuals in British Columbia, nirmatrelvir and ritonavir treatment was associated with reduced risk of COVID-19 hospitalization or death in CEV individuals, with the greatest benefit observed in severely immunocompromised individuals. No reduction in the primary outcome was observed in lower-risk individuals, including those aged 70 years or older without serious comorbidities.

Impact of the universal seasonal influenza vaccination policy in the province of Manitoba, Canada: A population-based, province-wide record-linkage study.

INTRODUCTION: In 2010, the government of the province of Manitoba, Canada introduced universal seasonal influenza vaccination policy (USIVP), providing free-of-charge vaccination to all registered residents of the province at least six months of age. Impact of the policy on seasonal influenza vaccine (SIV) uptake (receipt of vaccine) in Manitoba remains unclear, as there is a lack of published evaluations. METHODS: We conducted an ecological study, utilizing population-wide data from several linked de-identified Manitoba Health and Seniors Care administrative health databases. The study period was from 2000/01-2019/20 influenza seasons. The primary exposure was USIVP (five influenza seasons pre-policy [2005/06-2009/10] compared with post-policy [2010/11-2014/15]). The outcome was SIV uptake. We conducted pre/post logistic regression analysis stratified by age group (<5-, 5-17-, 18-44-, 45-64-, ≥65-year-olds) and certain population socioeconomic and health-related characteristics. Results are adjusted odds ratios with associated 95 % confidence intervals. RESULTS: We observed significantly increased adjusted odds of SIV uptake post-policy relative to pre-policy in all age groups except ≥65-year-olds already covered from inception of the vaccination programme. The adjusted odds ratios ranged from 0.76 (0.75-0.76) among ≥65-year-olds to 2.15 (2.13-2.18) among 5-17-year-olds, and were largely homogeneous within age groups across sex, income quintiles, regions of residence, and categories of number of visits to primary care physician/hospitalization one year prior to an influenza season except among <5- and 5-17-year-olds. These findings were mostly consistent irrespective of sex and region of residence although there was variability across income quintiles in Northern Manitoba region. CONCLUSIONS: Introduction of the USIVP in Manitoba was followed by a significant increase in SIV uptake in the five years post policy among <65-year-olds, with similar increased relative odds of vaccination observed within age groups across subpopulations. The observed variations in the relative odds of vaccination across income quintiles in Northern Manitoba region requires administrative attention.

Barriers and facilitators influencing the management of academic detailing programs: A descriptive analysis of four programs.

BACKGROUND: Educating prescribers is a key strategy to reduce inappropriate prescribing in selection, dose, type, timing, and duration. Academic detailing (AD) is a form of continuing medical education to educate prescribers. AD programs have been established in Canada, Australia, the United States, and other countries. Each program operates uniquely to reflect its local context and resources. It remains unclear how AD programs in universal health care systems differ from each other in their program components and experiences. OBJECTIVES: To compare AD programs focusing on components of resources, activities, and services and to identify factors influencing program efficiency during the processes of program management, topic development, and service delivery among the selected Canadian and international AD programs. METHODS: We adopted a process evaluation methodology with semistructured interviews and documents. We selected 4 well-established AD programs through an iterative discussion with the BC Ministry of Health: three provincial AD programs in the Canadian provinces of British Columbia, Ontario, and Saskatchewan, and an Australian program based in the State of South Australia. We invited one leader from each program to attend a 1-hour teleconferencing interview. RESULTS: The 4 programs shared similarities of public government funding while differed in their operation models (centralized vs. decentralized), employment of detailers (part-time vs. full-time; hired by AD programs vs. hired by partnered multidisciplinary primary care teams) and staff who developed topics (detailers vs. nondetailers). The most common barriers were funding and reaching new participants, followed by team connection, detailer training resources, summarizing skills, and AD session scheduling. The most common facilitators were participant retention, participant recruitment through partnership, and easy access sessions. CONCLUSION: AD programs can potentially guide a prescriber's choice of drug. A program's operation can be impacted by its access to resources and participants, activities, and service design.

Signal and Noise: Proton Pump Inhibitors and the Risk of Dementia?

The association between proton pump inhibitor (PPI) use and dementia remains controversial. This cohort study re-examines this issue, addressing shortcomings identified in previous publications using a population-based and a high-dimension propensity-score matched cohort to follow patients for up to 22 years. Cox regression models using baseline characteristics, a lag period, and time-varying variables were used to examine the risk of dementia by cumulative PPI exposure. High-dose PPI users (> 180 days of use) had significantly higher risk of dementia in crude Cox models. After adjustment for medical diagnoses and prescription drug use, these associations disappeared. Among high-dose users starting PPI therapy between 46 and 55 years old, the unadjusted hazard ratio (HR) was 1.55 (95% confidence interval (CI) 1.14, 2.10); the adjusted hazard ratio (aHR) was 1.10 (95% CI 0.80, 1.51). For high-dose users starting therapy between 56 and 65 years, HR = 1.22 (95% CI1.03, 1.44); aHR = 0.99 (95% CI 0.83, 1.17). High-dose users between the ages of 66 and 75 years had no association with the risk of dementia. The use of lag models or time-varying parameters similarly found some association with dementia in crude, but not multivariable Cox models. Although high-dose PPI users were more likely to develop dementia, they were more likely to be diagnosed with dementia risk factors, such as diabetes and cardiovascular disease, which are risk factors for dementia. Controlling for these conditions using multivariable models or a propensity-score matched cohort eliminated this association.

Second-Generation Long-Acting Injectable Antipsychotics and the Risk of Treatment Failure in a Population-Based Cohort.

Introduction: Second-generation long-acting injectable antipsychotics (SG-LAIAs) may improve outcomes compared to other antipsychotics. Real-world studies using linked administrative databases play an important role in assessing the comparative effectiveness of antipsychotic medications. Methods: We used a prevalent new-user design in a population-based cohort of antipsychotic users with diagnosis of a psychotic disorder to compare the primary outcome of treatment failure, defined as psychiatric hospitalization, completed suicide, incarceration, or treatment discontinuation. Additional outcomes were all-cause mortality. SG-LAIA users were matched on a 1:1 basis with other antipsychotic users based on the time-conditional propensity score, calendar time, and prior antipsychotic exposure. Results: The use of LAIAs was not associated with a lower risk of treatment failure than other antipsychotics (adjusted hazard ratio 1.07 and 95% confidence interval 0.98-1.15) but did reduce all-cause mortality (adjusted hazard ratio 0.69 and 95% confidence interval 0.48-0.99). Monotherapy with LAIAs was superior to other antipsychotic monotherapy (adjusted hazard ratio for treatment failure 0.83 and 95% confidence interval 0.78-0.89), and LAIAs were superior to other antipsychotics in antipsychotic-naïve users (adjusted hazard ratio for treatment failure 0.57 and 95% confidence interval 0.47-0.70). Conclusion: In this population-based cohort, SG-LAIAs reduced the risk of treatment failure in incident new users but not in prevalent new users.

Long-Acting Injectable Antipsychotics in a Prescription Claims Data Source: A Validation Study.

BACKGROUND: The effectiveness of long-acting injectable antipsychotics (LAIAs) has been demonstrated in studies using prescription claims data. However, the validity of claims data for LAIAs has not been established. OBJECTIVE: We aimed to validate date dispensed, quantity dispensed and days supplied fields in prescription claims data, and to compare claims- and medical record-derived persistence estimates. METHODS: We evaluated LAIA dispensations in the Drug Programs Information Network prescription claims database from Manitoba, Canada against a random sample of medical records. Adults with one or more LAIA prescription between April 2015 and March 2016 were eligible. Results were stratified by LAIA type (first-generation LAIA, risperidone LAI or paliperidone LAI). Persistence estimates were assessed using Kaplan-Meier survival analysis and proportion of patients covered method. RESULTS: Claims data had high positive predictive value, ranging from 80.0% (95% CI 51.9-95.7) to 100.0% (95% CI 89.7-100.0), but low negative predictive value, ranging from 0.0% (95% CI 0.0-2.5) to 62.5% (95% CI 40.6-81.2). Quantity dispensed and days supplied exactly matched dose and dosing interval, respectively, for 99.7% and 97.1% of risperidone LAI doses, 100.0% and 76.6% of paliperidone doses, and 8.9% and 28.3% of first-generation LAIA doses. There were no significant differences in claims-derived versus medical record-derived persistence estimates. CONCLUSIONS: Quantity dispensed and days supplied provide valid estimates of dose and dosing interval for second-generation LAIAs, but underestimated these parameters for first-generation LAIAs. However, a large proportion of medical record-confirmed doses were missing from claims data, and dose and dosing interval are underestimated in claims data.

Off-label postpartum use of domperidone in Canada: a multidatabase cohort study.

BACKGROUND: Trends in off-label postpartum use of domperidone and the impact of safety advisories on its use remain unknown. Our objectives were to describe postpartum use of domperidone in Canada, to evaluate the impact of Health Canada advisories on prescribing patterns, and to describe the association between domperidone use and a composite end point of sudden cardiac death or ventricular tachycardia (VT) among postpartum patients. METHODS: We conducted a multidatabase cohort study involving pregnant patients with live births between 2004 and 2017 using administrative health databases from 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba and Ontario). We excluded patients with less than 1 year of prepregnancy database history and with approved indications for domperidone. We assessed domperidone use in the 6 months postpartum and the impact of the 2012 and 2015 Health Canada advisories on prescribing via interrupted time series analysis. We estimated crude rates of VT and sudden cardiac death. RESULTS: We included 1 190 987 live births. Mean maternal age was 28.6 (standard error 0.6) years. Domperidone use increased over time, from 7% in 2003-2005 to 12% in 2009-2011, when it plateaued. The 2012 advisory was followed by a drop in use and a reduction in slope, and the 2015 advisory had a more modest impact. Crude analysis suggests that domperidone may be associated with increased VT or sudden cardiac death (0.74 v. 0.37 per 10 000 person-years; difference per 10 000 person-years: 0.37, 95% confidence interval -0.67 to 1.41). INTERPRETATION: Postpartum domperidone use increased between 2004 and 2017, with prescribing attenuated after Health Canada advisories and a very low absolute rate of VT or sudden cardiac death. These findings suggest that Health Canada advisories affected prescribing; any potential increase in VT or sudden cardiac death with use of domperidone is small and could not be confirmed in this large study STUDY REGISTRATION: ClinicalTrials.gov, no. NCT04024865.

Effectiveness and safety among direct oral anticoagulants in nonvalvular atrial fibrillation: A multi-database cohort study with meta-analysis.

AIMS: There are conflicting signals in the literature about comparative safety and effectiveness of direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF). METHODS: We conducted multicentre matched cohort studies with secondary meta-analysis to assess safety and effectiveness of dabigatran, rivaroxaban and apixaban across 9 administrative healthcare databases. We included adults with NVAF initiating anticoagulation therapy (dabigatran, rivaroxaban or apixaban), and constructed 3 cohorts to compare DOACs pairwise. The primary outcome was pooled hazard ratio (pHR) of ischaemic stroke or systemic thromboembolism. Secondary outcomes included pHR of major bleeding, and a composite of stroke, major bleeding, or all-cause mortality. We used proportional hazard Cox regressions models, and pooled estimates were obtained with random effect meta-analyses. RESULTS: The cohorts included 73 414 new users of dabigatran, 92 881 of rivaroxaban, and 61 284 of apixaban. After matching, the pHRs (95% confidence intervals) comparing rivaroxaban initiation to dabigatran were: 1.11 (0.93, 1.32) for ischaemic stroke or systemic thromboembolism, 1.26 (1.09, 1.46) for major bleeding, and 1.17 (1.05, 1.30) for the composite endpoint. For apixaban vs dabigatran, they were: 0.91 (0.74, 1.12) for ischaemic stroke or systemic thromboembolism, 0.89 (0.75, 1.05) for major bleeding, and 0.94 (0.78 to 1.14) for the composite endpoint. For apixaban vs rivaroxaban, they were: 0.85 (0.74, 0.99) for ischaemic stroke or systemic thromboembolism, 0.61 (0.53, 0.70) for major bleeding, and 0.82 (0.76, 0.88) for the composite endpoint. CONCLUSION: We found that apixaban use is associated with lower risks of stroke and bleeding compared with rivaroxaban, and similar risks compared with dabigatran.

Comparative effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists in nonvalvular atrial fibrillation: a Canadian multicentre observational cohort study.

BACKGROUND: Direct oral anticoagulants (DOACs) have widely replaced warfarin for stroke prevention in nonvalvular atrial fibrillation. Our objective was to compare the safety and effectiveness of DOACs (dabigatran, rivaroxaban, apixaban) versus warfarin for stroke prevention in nonvalvular atrial fibrillation in the Canadian setting. METHODS: We conducted a population-based observational multicentre cohort study with propensity score matching and subsequent meta-analysis. We used health care databases from 7 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec and Nova Scotia). Patients with nonvalvular atrial fibrillation who initiated anticoagulation therapy in 2009-2017 were matched to an equal number who initiated warfarin. The primary outcome was the pooled hazard ratio (HR) for ischemic stroke or systemic embolization. Secondary outcomes included pooled HRs for major bleeding; a composite outcome of stroke, systemic embolization, major bleeding and all-cause mortality; and myocardial infarction. We modelled HRs using proportional hazard Cox regression with inverse probability of censoring weights, and estimated pooled HRs with random-effect meta-analyses. RESULTS: We included 128 273 patients who initiated anticoagulation with a DOAC (40 503 dabigatran, 49 498 rivaroxaban and 38 272 apixaban) and 128 273 patients who initiated anticoagulation with warfarin. The pooled HR for ischemic stroke or systemic embolization comparing DOACs to warfarin was 1.02 (95% confidence interval [CI] 0.87 to 1.19). Direct oral anticoagulants were associated with lower rates of major bleeding (pooled HR 0.81, 95% CI 0.69 to 0.97), the composite outcome (pooled HR 0.81, 95% CI 0.74 to 0.89) and all-cause mortality (pooled HR 0.81, 95% CI 0.78 to 0.85). INTERPRETATION: In this real-world study, DOACs were associated with similar risks of ischemic stroke or systemic embolization, and lower risks of bleeding and total mortality compared to warfarin. These findings support the use of DOACs for anticoagulation in nonvalvular atrial fibrillation. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT03596502.

Prenatal antibiotic exposure and risk of attention-deficit/hyperactivity disorder: a population-based cohort study.

BACKGROUND: Abnormal microbiota composition induced by prenatal exposure to antibiotics has been proposed as a potential contributor to the development of attention-deficit/hyperactivity disorder (ADHD). We examined the association between prenatal antibiotic exposure and risk of ADHD. METHODS: We conducted a population-based retrospective cohort study of children born in Manitoba, Canada, between 1998 and 2017 and their mothers. We defined exposure as the mother having filled 1 or more antibiotic prescriptions during pregnancy. The outcome was diagnosis of ADHD in the offspring, as identified in administrative databases. We estimated hazard ratios (HRs) using Cox proportional hazards regression in the overall cohort, in a separate cohort matched on high-dimensional propensity scores and in a sibling cohort. RESULTS: In the overall cohort, consisting of 187 605 children, prenatal antibiotic dispensation was associated with increased risk of ADHD (HR 1.22, 95% confidence interval [CI] 1.18-1.26). Similar results were observed in the matched cohort of 129 674 children (HR 1.20, 95% CI 1.15-1.24) but not in the sibling cohort (HR 1.06, 95% CI 0.99-1.13). Two negative-control analyses indicated a positive association with ADHD despite the lack of a reasonable biological mechanism, which suggested that the observed association between prenatal antibiotic dispensation and risk of ADHD was likely due to confounding. INTERPRETATION: In our study, prenatal antibiotic exposure was not associated with increased risk of ADHD in children. Although the risk was higher in the overall and matched cohorts, it was likely overestimated because of unmeasured confounding. Future studies are warranted to examine other factors affecting microbiota composition in association with risk of ADHD.

Trends in the Use of Long-Acting Injectable Antipsychotics in the Province of Manitoba, Canada.

BACKGROUND: Long-acting injectable antipsychotics (LAIAs) have advantages over oral antipsychotics but are not widely used. We aimed to evaluate the impact of market entry of second-generation LAIAs on prescribing trends. METHODS: We used administrative health databases to describe trends in LAIA use from 1995 to 2015 in the Canadian province of Manitoba. Age- and sex-specific incident and prevalent use were determined using prescription dispensation records for the entire population. We used interrupted time series analysis with Poisson regression to estimate change in LAIA use attributable to the market entry of the second-generation LAIA risperidone. RESULTS: We observed 3380 prevalent LAIA users and 2375 incident users in our cohort. Long-acting injectable antipsychotic use was higher in males. Incidence proportions declined from 21.5 users per 100,000 in 1996 to 4.8 in 2004 and then climbed to 14.7 by 2015. First-generation LAIA use peaked at 94.6 prevalent users per 100,000 in 1998 but fell to 40.9 in 2015. Long-acting injectable antipsychotic use increased 1.4% per quarter after the market entry of risperidone long-acting injectable. CONCLUSIONS: Risperidone risperidone long-acting injectable market entry had a positive impact on LAIA prescribing.

Antibiotic Exposure in the First Year of Life and the Risk of Attention-Deficit/Hyperactivity Disorder: A Population-Based Cohort Study.

Early childhood antibiotic exposure induces changes in gut microbiota reportedly associated with the development of attention-deficit/hyperactivity disorder (ADHD). We conducted a population-based cohort study to examine the association between antibiotic use in the first year of life and ADHD risk. We included children born in Manitoba, Canada, between 1998 and 2017. Exposure was defined as having filled 1 or more antibiotic prescriptions during the first year of life. ADHD diagnosis was identified in hospital abstracts, physician visits, or drug dispensations. Risk of developing ADHD was estimated using Cox proportional hazards regression in a high-dimensional propensity score-matched cohort (n = 69,738) and a sibling cohort (n = 67,671). ADHD risk was not associated with antibiotic exposure in the matched-cohort (hazard ratio = 1.02, 95% confidence interval: 0.97, 1.08) or in the sibling cohort (hazard ratio = 0.96, 95% confidence interval: 0.89, 1.03). In secondary analyses of the matched cohort, ADHD risk increase was observed in those exposed to 4 or more antibiotic courses or a duration longer than 3 weeks. These associations were not observed in the sibling cohort. We concluded that antibiotic exposure in the first year of life does not pose an ADHD risk on a population level.

Prenatal antibiotics exposure and the risk of autism spectrum disorders: A population-based cohort study.

BACKGROUND: Prenatal antibiotic exposure induces changes in infants' gut microbiota composition and is suggested as a possible contributor in the development of autism spectrum disorders (ASD). In this study, we examined the association between prenatal antibiotic exposure and the risk of ASD. METHODS: This was a population-based cohort study utilizing the Manitoba Population Research Data Repository. The cohort included 214 834 children born in Manitoba, Canada between April 1, 1998 and March 31, 2016. Exposure was defined as having filled one or more antibiotic prescription during pregnancy. The outcome was autism spectrum disorder diagnosis. Multivariable Cox proportional hazards regression was used to estimate the risk of developing ASD in the overall cohort and in a sibling cohort. RESULTS: Of all subjects, 80 750 (37.6%) were exposed to antibiotics prenatally. During follow-up, 2965 children received an ASD diagnosis. Compared to children who were not exposed to antibiotics prenatally, those who were exposed had a higher risk of ASD: (adjusted HR 1.10 [95% CI 1.01, 1.19]). The association was observed in those exposed to antibiotics in the second or third trimester (HR 1.11 [95% CI 1.01, 1.23] and 1.17 [95% CI 1.06, 1.30], respectively). In the siblings' cohort, ASD risk estimate remained unchanged (adjusted HR 1.08 [95% CI 0.90, 1.30], although it was not statistically significant. CONCLUSIONS: Prenatal antibiotic exposure is associated with a small increase in the risk of ASD. Given the potential of residual confounding beyond what it was controlled through our study design and because of possible confounding by indication, such a small risk increase in the population is not expected to be clinically significant.

Annual trends in prevalence and incidence of autism spectrum disorders in Manitoba preschoolers and toddlers: 2004-2015.

OBJECTIVES: Autism spectrum disorders (ASD) are among the leading causes of disabilities in children. We examined the annual prevalence and incidence rate of ASD between 2004 and 2015 in children aged 1 to 5 years residing in Manitoba. METHODS: A population-based study was conducted using the Manitoba Population Research Data Repository. The study included children aged 1 to 5 years residing in Manitoba between 2004 and 2015. Standard identification algorithm was used to identify ASD cases from hospital abstracts and medical claims. Annual prevalence and incidence rates were calculated for the overall population and then stratified according to sex, region, and socio-economic status (SES). Multivariable negative binomial regression models, adjusted for sex, region, and SES, were used to examine changes in prevalence and incidence over study years. RESULTS: Among children aged 1 to 5 years, 1685 ASD cases were diagnosed between 2004 and 2015. The crude ASD prevalence increased from 0.46% in 2004 to 0.97% in 2015 (p = 0.002). The crude incidence rate increased from 0.16% in 2004 to 0.39% in 2015 (p = 0.002). The increase in ASD prevalence and incidence was observed in all subgroups based on sex, region, and SES. The adjusted negative binomial model showed an annual relative risk increase, since 2004, for both prevalence and incidence of 1.69 (95% CI 1.56-1.83) and 1.84 (95% CI 1.62-2.09), respectively. CONCLUSION: During the period from 2004 to 2015, both prevalence and incidence rates of diagnosed ASD in preschoolers and toddlers residing in Manitoba increased significantly.

Treating Children with ASD: The Perspective of Caregivers.

PURPOSE: Treatment of Autism Spectrum Disorders (ASD) is challenging. Parents/caregivers' perspective on the effectiveness of therapies and services available to their children is important but neglected in the literature on ASD.  This study investigated such perspective through questionnaire-guided interviews with a group of parents in the province of Manitoba (Canada). A secondary objective of the study was to explore how health care professionals and specifically pharmacists can assist in providing better care to children with ASD.  Methods: Informed consent was obtained from all participants. Data on diagnoses and prescribed medications were collected from medical charts. Parents/caregivers completed questionnaires during interviews scheduled at their convenience. Specific questions were asked to gather caregivers/parents' perspectives on the effectiveness of medications and non-pharmacological interventions in controlling symptoms experienced by their children.  Information on access to education and health services was also assessed. Common themes were identified using thematic analysis. RESULTS: All children attended school, 88% were males, 50% experienced eating/sleeping difficulties; 69% reported Attention Deficit Hyperactivity Disorder comorbidity. Risperidone was reported to be effective in controlling aggressive behaviours. Methylphenidate and aripiprazole were often discontinued. Melatonin and occupational therapy services were said to be very useful. Access to behavioural therapy was often limited. Parents were concerned about lack of trained professionals in schools, limited understanding of their children's needs, and uncertainty for the future. CONCLUSIONS: Better education and awareness are necessary to help ASD children and their families. Pharmacists should explore opportunities to provide better services. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Moving towards Universal Coverage of Direct-Acting Antiviral Therapies for Hepatitis C Infection in Canada: An Environmental Scan of Canadian Provinces and International Jurisdictions.

BACKGROUND: Direct-acting antivirals (DAAs) have become the standard treatment for patients with chronic hepatitis C infections because of their high cure rates and favourable side effect profiles; however, access to this new class of agents has been limited because of its high cost.  Public payers across Canada have implemented strict criteria for drug coverage in order to contain expenditures. Efforts have been made to improve access to medication for this high-burden condition. Recent coverage criteria across national and international jurisdictions have been compared. METHODS: Coverage criteria for several DAAs were reviewed by accessing Canadian provincial drug formularies. International coverage (e.g., Europe, Australia, United States, Egypt, India) was reviewed by searching available literature. RESULTS: Coverage criteria vary across Canada. By April 2018, most Canadian jurisdictions had removed the stage 2 liver fibrosis requirement for patients to be eligible for coverage. Internationally, patients' access to DAAs differs significantly. Many jurisdictions restrict DAA prescribing authority to specialists and request documentation of chronic hepatitis C. In the US, considerable gaps of coverage are identifiable and patients might face significant financial burden to receive treatment. CONCLUSION: DAAs appear to be generally accessible through public drug plans in Canada compared to other countries.

Early childhood antibiotics use and autism spectrum disorders: a population-based cohort study.

Background: Changes in microbiota composition as a result of antibiotics use in early life has been proposed as a possible contributor in the aetiology of autism spectrum disorders (ASD). We aimed to examine the association between early life antibiotic exposure and risk of ASD. Methods: This was a population-based cohort study which included all live births in Manitoba, Canada, between 1 April 1998 and 31 March 2016. We used administrative health data from the Manitoba Population Research Data Repository. Exposure was defined as having filled one or more antibiotic prescription during the first year of life. The main outcome was ASD diagnosis. Cox proportional hazards regression models were used to estimate the risk of developing ASD in the overall population and in a sibling cohort. Results: Of all subjects in the cohort (n = 214 834), 94 024 (43.8%) filled an antibiotic prescription during the first year of life. During follow-up, 2965 children received an ASD diagnosis. Compared with children who did not use antibiotics during the first year of life, those who received antibiotics had a reduced risk of ASD [adjusted hazardz ratio (HR) 0.91, 95% confidence interval (CI) 0.84-0.99). Number of treatment courses and cumulative duration of antibiotic exposure were not associated with ASD. In the sibling-controlled analysis, early life antibiotic exposure was not associated with ASD (adjusted HR 1.03, 95% CI 0.86-1.23). Conclusions: Our findings suggested no clinically significant association between early life antibiotics exposure and risk of autism spectrum disorders, and should provide reassurance to concerned prescribers and parents.

Training Needs of Manitoba Pharmacists to Increase Application of Assessment and Prescribing for Minor Ailments into Practice: A Qualitative and Quantitative Survey.

Current literature demonstrates the positive impact of pharmacists prescribing medication on patient outcomes and pharmacist perceptions of the practice. The aim of this study was to understand the factors affecting prescribing practices among Manitoba pharmacists and identify whether additional training methods would be beneficial for a practice behavior change. A web-based survey was developed and participation was solicited from pharmacists in Manitoba. Descriptive statistics were calculated to summarize the frequency of demographic characteristics. Chi-square tests were used to explore possible correlations between variables of interest and thematic analysis of qualitative data was completed. A total of 162 participants completed the survey. The response rate was 12.3%. Of those who had met the requirements to prescribe, none were doing so on a daily basis and 23.5% had not assessed or prescribed since being certified. Respondents identified the top barriers for providing this service as a lack of sufficient revenue and a lack of time. Qualitative analysis of responses identified additional barriers including a limiting scope and inadequate tools. Approximately half (54.4%) of respondents expressed that additional training would be of value. The themes identified from the survey data suggest that practice-based education would help pharmacists apply skills. In addition, expansion of prescribing authority and strategies addressing remuneration issues may help overcome barriers to pharmacists prescribing within Manitoba.