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Purpose: During the COVID-19 pandemic, public health measures were implemented, yet it is unknown whether these measures affected medication access in those with schizophrenia (SCZ). This study aimed to assess whether the antipsychotic utilization in SCZ changed during the pandemic., Methods: We used dispensed prescription drug data from the Canadian province of Manitoba in individuals with SCZ using linked administrative data from the Manitoba Population Research Data Repository. The quarterly incident and prevalent dispensation of antipsychotics at two periods were compared with the expected trend (April 1, 2015 to April 1, 2020 and 2021) using linear autoregression. We stratified the primary results by age and sex and examined multiple subgroups., Results: There were 9045 individuals with SCZ in the first fiscal quarter of 2020. The prevalent use of the most common antipsychotics were: olanzapine (206.7/1000), risperidone (190.8/1000), quetiapine (174.4/1000), and clozapine (100.9/1000). The overall prevalent use of antipsychotics remained stable during the pandemic compared with the expected trend. A significant decrease in the incident use in April-June 2020 (estimate: -1.3, 95%CI:-2.2,-0.3) was noted compared with the expected. A significantly higher incidence of atypical antipsychotics (estimate: 1.4, 95%CI: 0.2,2.5) and risperidone separately (estimate: 1.8, 95%CI: 0.2,3.3) was noted in 2021 compared with expected., Conclusion: This study found a decline in the receipt of antipsychotics for people with SCZ during the initial implementation of COVID-19 public health measures, particularly on the overall incidence. Future work on investigating the impact of these trends on SCZ outcomes is needed to inform future pandemic-related policies., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Human papillomavirus (HPV) vaccination rates among females are lower than the World Health Organization target and vaccination rates specifically among adult females are even much lower., Methods: We systematically evaluated individual socioeconomic and health-related characteristics associated with HPV vaccination initiation and vaccination series completion among adult females (PROSPERO: CRD42023445721). We performed a literature search on December 14, 2022, and supplemented the search on August 1, 2023. We pooled appropriate multivariable-adjusted results using an inverse variance random-effects model and expressed the results as odds ratios with associated 95 % confidence intervals. A point pooled significantly increased/decreased odds of 30-69 % was regarded to be strongly associated, and ≥ 70 % was very strongly associated., Results: We included 63 cross-sectional studies. There were strongly increased odds of vaccination initiation among White women compared with Black or Asian women, and those with higher education, health insurance, a history of sexually transmitted infection (STI), receipt of influenza vaccination in the preceding year, not married/cohabiting, not smoking, using contraception, and having visited a healthcare provider in the preceding year. We observed very strongly increased odds of vaccination initiation among those younger and having been born in the country of study. Similarly, there were strongly increased odds of completing the vaccination series for the same variables as initiating vaccination, except for higher education, prior STI, smoking and contraception use. Additional variables associated with strongly increased odds of vaccination series completion not seen in initiation were higher annual household income, being lesbian/bisexual, and having a primary care physician. We observed very strongly increased odds of vaccination series completion similar to vaccination initiation but including for White compared with Black women, higher education, and prior cervical cancer screening., Conclusions: These individual characteristics may be the key to identifying women at increased risk of not being vaccinated against HPV and could inform targeted messaging to drive HPV vaccination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This study received no funding., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., (© 2024. The Author(s) under exclusive license to The Canadian Public Health Association.)

Aims: We aimed to systematically synthesize the current published literature on neonatal growth outcomes associated with antiseizure medication (ASM) use during pregnancy., Methods: We searched seven databases, from inception to 23 March 2022. We investigated small for gestational age (SGA) and low birth weight (LBW) as primary outcomes and birth weight, birth height, cephalization index and head circumference as secondary outcomes. The primary analysis included pregnant people exposed to any ASM compared with unexposed pregnant people. Subgroup analysis included ASM class analysis, within epilepsy group analysis and polytherapy compared to monotherapy., Results: We screened 15 720 citations and included 65 studies in the review. Exposed pregnant people had a significantly increased risk of SGA relative risk (RR) 1.33 (95% CI 1.18 to 1.50, I 2 74%), LBW RR 1.54 (95% CI 1.33 to 1.77, I 2 67%), and decreased birth weight with a mean difference (MD) of -118.87 (95% CI -161.03 to -76.71, I 2 42%) g. A non-significant risk change in birth height and head circumference was observed. In subgroup analysis, ASM polytherapy, within epilepsy and ASM class analysis were also associated with an increased risk of SGA and LBW., Conclusions: This meta-analysis demonstrates that pregnant people exposed to ASMs have a significantly increased risk of adverse fetal growth outcomes including SGA and LBW and decreased birth weight compared to unexposed pregnant people. Polytherapy was associated with higher risks compared to monotherapy. Additional studies are warranted on specific ASM risks., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objective: To examine the quarterly incidence and prevalence of medications for opioid use disorder (OUD) and alcohol use disorder (AUD) from 2015 to 2021., Methods: A retrospective population-wide observational study in Manitoba, Canada, was conducted using administrative claims data from the Manitoba Centre for Health Policy to examine the incidence and prevalence of OUD (methadone, buprenorphine-naloxone, buprenorphine) or AUD medications (naltrexone, acamprosate, disulfiram) per 10,000 individuals in each quarter between January 1, 2015, and December 31, 2021., Results: There were 1179 and 451 individuals who received at least one prescription for OUD and AUD, respectively, in the first quarter of 2020. The prevalence of OUD medications more than doubled from 6.3 to 14.3 per 10,000 from January 1, 2015, to December 31, 2021. Likewise, AUD medication prevalence increased almost 10-fold from 0.68 to 6.5 per 10,000 from January 1, 2015, to December 31, 2021, primarily due to naltrexone. The incidence of AUD prescription use increased 8.6-fold from 0.29 to 2.51 per 10,000 during the study period. In contrast, the incidence of opioid agonist therapy declined from 2.1 per 10,000 in the first quarter of 2015 to 0.53 per 10,000 the first quarter of 2016, primarily due to methadone. Whereas methadone incidence declined, buprenorphine-naloxone incidence increased almost 15-fold during the study period., Conclusion: An increase in both AUD medication prevalence and incidence in addition to an increase in buprenorphine-naloxone incidence was observed. These findings reflect an increase in the uptake of medications for treating AUD and OUD following changes to improve coverage and access to these medications., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Addiction Medicine.)

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Mahmud has received unrestricted research grants from GlaxoSmithKline, Merck, Pfizer, Sanofi Pasteur, and Roche-Assurex for unrelated studies, and fees as a consultant and advisory board member for GlaxoSmithKline, Merck, Pfizer, Sanofi Pasteur, and Seqirus. Righolt has received an unrestricted research grant from Pfizer for an unrelated study. The other authors declare that they have no conflicts of interest.]., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Seasonal influenza vaccine (SIV) uptake (receipt of vaccine) in Manitoba, Canada is consistently low notwithstanding vaccine availability and free-of-charge vaccination. Despite, there is a lack of published evidence on the determinants of uptake of the vaccine. We sought to assess the association between SIV uptake and certain population and primary care physician (PCP) characteristics in Manitoba., Methods: We conducted a longitudinal study utilizing Manitoba administrative health databases. We summarized SIV uptake from 2000/01-2019/20 influenza seasons across subpopulations defined by socioeconomic, health-related and PCP characteristics. Utilizing multivariable generalized estimating equation logistic regression models, we assessed the association between SIV uptake and the socioeconomic, health-related and PCP characteristics, stratified by age group (<5-, 5-17-, 18-44-, 45-64-, ≥65-year-olds) and sex. Results are adjusted odds ratios with associated 95 % confidence intervals., Results: SIV uptake percentage increased over time with 4.4 %, 13.1 %, 17.5 % and 21.7 % of < 5-year-olds, 2 %, 4.9 %, 9.7 % and 13.1 % of 5-17-year-olds, 5.4 %, 8.8 %, 10.7 % and 13.5 % of 18-44-year-olds, 16.8 %, 21.3 %, 23.6 % and 24.6 % of 45-64-year-olds receiving the SIV in 2000-2004, 2005-2009, 2010-2014 and 2015-2019, respectively. There was a decline among ≥ 65-year-olds from 58.5 % to 53.5 %. We observed a similar pattern across subpopulations. There were significantly increased odds of SIV uptake among females within the age groups ≥ 18 years, in higher income quintiles, mostly with increased contact with a PCP/hospitalization within age groups ≥ 18 years, among those who had older or female PCPs (the opposite observation among ≥ 65-year-olds) and whose PCP administered at least one SIV in prior influenza season. These observations were largely consistent irrespective of sex., Conclusion: SIV uptake in Manitoba appears to increase with age, and many socioeconomic, health-related and PCP characteristics appear to be associated with it. These findings may inform targeted vaccination programs to optimize influenza vaccination in Manitoba and similar Canadian jurisdictions., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Mahmud has received unrestricted research grants from GlaxoSmithKline, Merck, Pfizer, Sanofi Pasteur, and Roche-Assurex for unrelated studies, and fees as a consultant and advisory board member for GlaxoSmithKline, Merck, Pfizer, Sanofi Pasteur, and Seqirus. Righolt has received an unrestricted research grant from Pfizer for an unrelated study. The other authors declare that they have no conflicts of interest]., (© 2024 The Authors.)

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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mahmud has received unrestricted research grants from GlaxoSmithKline, Merck, Pfizer, Sanofi Pasteur, and Roche-Assurex for unrelated studies, and fees as a consultant and advisory board member for GlaxoSmithKline, Merck, Pfizer, Sanofi Pasteur, and Seqirus. Righolt has received an unrestricted research grant from Pfizer for an unrelated study. The other authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Hepatitis C virus (HCV) infection is a major cause of liver-related morbidity and mortality worldwide. Epidemiological data of HCV infection in the Canadian province of Manitoba are limited., Methods: A population-based retrospective study was conducted using data from the Manitoba Centre for Health Policy repository. Using the test results provided by the Cadham provincial laboratory, individuals in Manitoba with a diagnosis of HCV infection were identified. Annual prevalence and incidence rates (crude and standardized) were calculated for the overall population and stratified by sex, regional health authority (RHA), residence area, income quintile, and special population groups (children, older adults, and pregnant persons)., Results: A total of 8,721 HCV cases were diagnosed between 1998 and 2018 in Manitoba. Overall crude HCV incidence and prevalence were estimated as 0.03% and 0.37% during the study period, respectively. No significant change was observed in the standardized HCV incidence rate (per 100,000) during the study period (54.3 in 1998 and 54.8 in 2018). However, the standardized HCV prevalence (per 100,000) increased from 52.5 (95% CI 39.2-68.7) in 1998 to 655.2 (95% CI 605.9-707.3) in 2018. An overall average incidence rate based on sex, RHA, region, income, and special population groups was observed to be higher in males (40.1), Winnipeg RHA (42.7), urban region (42.3), low-income quintiles (78.5), and pregnant persons (94.3), respectively., Conclusion: Although incidence rates of HCV infection in Manitoba appeared to have initially declined, rates showed an upward trend by the end of the study period while prevalence increased steadily., Competing Interests: SK Gudi received funding from the Drug Safety and Effectiveness Cross-Disciplinary Training (DSECT) program, as well as meeting support from the Canadian Network for Observational Drug Effect Studies (CNODES). C Osiowy received registration and accommodation for the Canadian Liver Meeting 2022 in Ottawa for being a speaker at the meeting. S Alessi-Severini was awarded the Leslie F. Buggey Professorship, which supported the present manuscript. She also received consulting fees from Jupiter Research Inc., (© Canadian Association for the Study of the Liver, 2023.)

Background: The coronavirus disease 2019 (COVID-19) pandemic and associated public health measures have shifted the way people access health care. We aimed to study the effects of the COVID-19 pandemic on psychotropic medication adherence., Methods: A retrospective cohort study using administrative data from the Manitoba Centre for Health Policy Manitoba Population Research Data Repository was conducted. Outpatients who received at least 1 prescription for an antidepressant, antipsychotic, anxiolytic/sedative-hypnotic, cannabinoid, lithium, or stimulants from 2015 to 2020 in Manitoba, Canada, were included. Adherence was measured using the proportion of individuals with a mean possession ratio of ≥0.8 over each quarter. Each quarter of 2020 after COVID-19-related health measures were implemented was compared with the expected trend using autoregression models for time series data plus indicator variables. Odds ratio of drug discontinuation among those previously adherent in 2020 was compared with each respective quarter of 2019., Results: There were 1,394,885 individuals in the study population in the first quarter of 2020 (mean [SD] age, 38.9 [23.4] years; 50.3% female), with 36.1% having a psychiatric diagnosis in the preceding 5 years. Compared with the expected trend, increases in the proportions of individuals adherent to antidepressants and stimulants were observed in the fourth quarter (October-December) of 2020 (both P < 0.001). Increases in the proportions of individuals with anxiolytic and cannabinoid adherence were observed in the third quarter (July-September) of 2020 (both P < 0.05), whereas a decrease was seen with stimulants in the same quarter ( P < 0.0001). No significant changes were observed for antipsychotics. All drug classes except lithium had decreases in drug discontinuation in previously adherent patients during the pandemic compared with 2019., Conclusions: Improved adherence to most psychotropic medications in the 9 months after public health restrictions were enacted was observed. Patients who were already adherent to their psychotropic medications were less likely to discontinue them during the pandemic., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Given the lack of evidence on how the COVID-19 pandemic impacted antiseizure medication (ASM) use, we examined the trends of ASMs before and during COVID-19., Methods: We conducted a population-based study using provincial-level health databases from Manitoba, Canada, between 1 June 2016 and 1 March 2021. We used interrupted time series autoregressive models to examine changes in the prevalence and incidence of ASM prescription rates associated with COVID-19 public health restrictions., Results: Among prevalent users, the COVID-19 pandemic led to a significant increase in new-generation ASMs with a percentage change of 0.09% ( p = 0.03) and a significant decrease in incidence use of all ASMs with a percentage change of -4.35% ( p = 0.04). Significant trend changes were observed in the prevalent use of new-generation ASMs ( p = 0.04) and incidence use of all ( p = 0.04) and new-generation ASMs ( p = 0.02). Gabapentin and clonazepam prescriptions contributed 37% of prevalent and 54% of incident use., Conclusion: With the introduction of public health measures during COVID-19, small but significant changes in the incident and prevalent use of ASM prescriptions were observed. Further studies are needed to examine whether barriers to medication access were associated with potential deterioration in seizure control among patients., Conference Presentation: The results from this study have been presented as an oral presentation at the 38th ICPE, International Society of Pharmacoepidemiology (ISPE) annual conference in Copenhagen., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lavu, Janzen, Aboulatta, Peymani, Haidar, Desrochers, Alessi-Severini and Eltonsy.)

Background: Conflicting evidence exists on the impact of the COVID-19 pandemic restrictions on preterm birth (PTB) and stillbirth rates. We aimed to evaluate changes in PTB and stillbirth rates before and during the pandemic period and assess the potential effect modification of socioeconomic status (SES)., Methods: Using the linked administrative health databases from Manitoba, Canada, we conducted a cross-sectional study among all pregnant women, comparing 3.5 years pre-pandemic (1 October 2016 to 29 February 2020) to the first year of the pandemic (1 March 2020 to 31 March 2021). We used generalised linear models to assess the quarterly rates of PTB (<37 weeks) and stillbirths. We calculated the predicted trends based on pre-pandemic period data. Finally, we evaluated the PTB and stillbirth rates among lower and higher SES pregnant women (average annual household income) using subgroup analysis and interaction models., Results: We examined 70 931 pregnancies in Manitoba during the study period. The risk of PTB increased by 7.7% (95%CI 1.01 to 1.13) and stillbirths by 33% (95% CI 1.08 to 1.64) during the pandemic period. Following COVID-19 restrictions implemented in March 2020, there were increases in the quarterly rates of both PTB (immediate increase (β 2 )=1.37; p=0.0247) and stillbirths (immediate increase (β 2 )=0.12; p=0.4434). Among the lower income groups, the pandemic restrictions resulted in an immediate relative increase in PTB and stillbirth rates by 20.12% (immediate increase (β 2 )=3.17; p=0.0057) and 27.19% (immediate increase (β 2 )=0.48; p=0.0852). However, over the pandemic, the overall PTB rate significantly decreased as a rebound effect by 0.85% per quarter (p=0.0004), whereas the overall stillbirth rate did not decrease significantly (slope decrease (β 3 ) =-0.01; p=0.8296) compared with the pre-pandemic period. The quarterly rates during the pandemic among the higher income group decreased by 0.39% (p=0.1296) for PTB and increased by 0.07% (p=0.1565) for stillbirth. We observed an effect modification by SES for PTB rates (p=0.047)., Conclusion: While the onset of COVID-19 pandemic restrictions was not associated with significant effects on stillbirth rates, we observed an immediate and rebound effect on PTB rates. The impact of COVID-19 on preterm birth was dependent on SES, with higher influence on families with lower SES. Further studies are needed to detect future trend changes during pandemic waves after 2021 and assess potential underlying mechanisms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Sex-based inequalities in healthcare have been exposed and amplified during the COVID-19 pandemic. However, few studies have reported sex differences in medication utilization and no studies have examined sex differences in prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and opioids utilization., Aim: To compare the utilization patterns of prescribed NSAIDs and opioids between males and females in Manitoba, Canada during the COVID-19 pandemic., Method: A cohort of incident and prevalent users of prescribed NSAIDs and opioids was created. Interrupted times series analysis using autoregressive models were used to evaluate the quarterly change in the prevalent and incident users before and after COVID-19 restrictions were applied (first quarter of 2020)., Results: COVID-19 restrictions were associated with a significant decrease in the utilization of prescribed NSAIDs and opioids in all users, followed by a revert to the pre-pandemic trends. Among female prevalent and incident NSAIDs users, there was a significant change in trend after COVID-19 restrictions were introduced (β 3  = 0.087 and 0.078, P = 0.023 and 0.028, respectively). However, there was non-significant change in trend among male prevalent and incident NSAIDs and opioids users during the pandemic., Conclusion: In this study, a significant sharp decline in the use of prescribed NSAIDs and opioids was shown in both sexes at the onset of the pandemic. However, a significant upward trend is observed in female NSAIDs users as restrictions began to be lifted., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The COVID-19 pandemic has led the Canadian provincial governments to take unprecedented measures, including restrictions to healthcare services and pharmacists. Limited evidence exists on changes in prescription trends in Canada during the pandemic period., Objectives: To examine the trend of prescription medications' utilization before and during COVID-19, among incident and prevalent users in the general population. We examined 18 major classes of medications., Methods: We used the administrative health databases from the province of Manitoba, Canada, to conduct a province-wide cross-sectional study. Incident and prevalent use was compared between two time periods; pre-COVID-19: July 2016-March 2020 and during COVID-19: April 2020-March 2021. Interrupted time series analysis using autoregressive models was used to quantify the change in level and slope in quarterly medication use among incident and prevalent users., Results: The quarterly study population ranged from 1,353,485 to 1,411,630 Manitobans. The most common comorbidities were asthma (26.67%), hypertension (20.64%), and diabetes (8.31%). On average, the pandemic restrictions resulted in a 45.55% and 12.17% relative decline in the aggregated utilization of all drugs among both incident and prevalent users, respectively. Subclass analysis showed a 46.83%, 23.05%, and 30.98% relative drop among incident users of antibiotics, cardiovascular drugs and opioids use, respectively. We observed a significant slope increase during COVID-19 among the quarterly cardiovascular, antidiabetics, alpha-1 blockers, and statins incident users compared to the pre-COVID-19 period. We noted a significant decrease in level among NSAIDs, opioids, and antibiotic prevalent users, however, no significant changes in slope were observed., Conclusion: Our findings show a significant impact of COVID-19 measures on prescription trends in the general population. The observed decline among several medication classes was temporary. Further research is needed to monitor prescription trends and better understand if those changes were associated with increased health services and worsened outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Aboulatta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Characteristics of patients using newer 2 nd and 3 rd line antidiabetic drugs in a real-world setting are poorly understood. We described the characteristics of new users of sodium-glucose co-transporter-2 inhibitors (SGLT-2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), and glucagon-like peptide-1 receptor agonists (GLP-1 RA) in Canada and the United Kingdom (UK) between 2016 and 2018., Methods: We conducted a multi-database cohort study using administrative health databases from 7 Canadian provinces and the UK Clinical Practice Research Datalink. We assembled a base cohort of antidiabetic drug users between 2006 and 2018, from which we constructed 3 cohorts of new users of SGLT-2i, DPP-4i, and GLP-1 RA between 2016 and 2018., Results: Our cohorts included 194,070 new users of DPP-4i, 166,722 new users of SGLT-2i, and 27,719 new users of GLP-1 RA. New users of GLP-1 RA were more likely to be younger (mean ± SD: 56.7 ± 12.2 years) than new users of DPP-4i (67.8 ± 12.3 years) or SGLT-2i (64.4 ± 11.1 years). In Canada, new users of DPP-4i were more likely to have a history of coronary artery disease (22%) than new users of SGLT-2i (20%) or GLP-1 RA (15%)., Conclusion: Although SGLT-2i, DPP-4i, and GLP-1 RAs are recommended as 2 nd or 3 rd line therapy for type 2 diabetes, important differences exist in the characteristics of users of these drugs. Contrary to existing guidelines, new users of DPP-4i had a higher prevalence of cardiovascular disease at baseline than new users of SGLT2i or GLP-1RA., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Janzen, Bolton, Leong, Kuo and Alessi-Severini.)

Objectives: The increasing spread of severe acute respiratory syndrome coronavirus-2 has prompted Canada to take unprecedented measures. The objective of this study was to examine the impact of the implemented public health measures on the incidence of COVID-19 in Manitoba., Results: Using the COVID-19 dataset, we examined the temporal trends of daily reported COVID-19 cases and the coinciding public health measures implemented from March 12, 2020 to February 28, 2022. We calculated the 7-day moving average and crude COVID-19 infection rate/100,000 Manitobans. Due to the restrictions applied, the infection rate decreased from 2.4 (April 1) to 0.07 infections (May 1, 2020). Between May 4 and July 17, 2020, the reported cases stabilized, and some restrictions were lifted. However, in November, the cases peaked with infection rate of 29. Additional restrictions were implemented, and the rate dropped to 3.6 infections on March 31, 2021. As of August 2021, 62.8% of eligible Manitobans received two vaccine doses. The infection rate increased to 128.3 infections on December 31, 2021 and mitigation measures were implemented. This study describes how physical distancing in conjunction with other containment measures can reduce the COVID-19 burden. Future studies into the extent of the implementation of the restrictions are necessary., (© 2022. The Author(s).)

Background: The coronavirus disease 2019 (COVID-19) pandemic and public health measures that took place have led to concerns regarding mental health and receipt of psychotropic medications. We aimed to study the changes in psychotropic medication dispensation rates before and during the COVID-19 pandemic in the general population. Methods: Administrative health data from the Canadian province of Manitoba was used to describe the quarterly incidence and prevalence of antipsychotics, antidepressants, and anxiolytic/sedative-hypnotics from January 1, 2015 to December 31, 2020. Individuals who received at least one prescription within each quarter were considered exposed to the medication. The denominator was the total population within each quarter. Incidence was defined as no receipt of medication in the 3 years prior to the quarter of interest. Autoregression models for time series data plus indicator variables were used to compare each quarter of 2020 after public health measures were implemented in March 2020 in relation to the expected trend. Analyses were stratified by age and sex. Results: There were 1,394,885 individuals in the first quarter of 2020, with a mean (SD) age of 38.9 (23.4) years, 50.3% were female, and 36.1% had a psychiatric diagnosis in the previous 5 years. A significant decrease was observed for incident antidepressant use ( p < 0.05 for both sexes and all age groups except for those 65 years and older) and anxiolytic use ( p < 0.05 for both sexes and all age groups except 80 years and older) in the second quarter (April-June) of 2020 compared to the expected trend. Females and those aged 40 years and older had a significantly higher incidence of antidepressant and antipsychotic use in the final quarter of 2020 compared to the expected trend ( p < 0.05). Conclusion: Our findings indicate a decrease in new prescriptions for antidepressants and anxiolytics in the 3 months after COVID-19 in-person restrictions were first implemented. We then observed an increase in the new use of antidepressants and antipsychotics at the end of 2020, in females and people aged 40 years and older, with the highest rates of use in the population 80 years and older., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Leong, Kowalec, Eltonsy, Bolton, Enns, Tan, Yogendran, Chateau, Delaney, Sareen, Falk, Spiwak, Logsetty and Alessi-Severini.)

Background: Evidence from developed countries demonstrates that the use of antiseizure medications (ASMs) has been increasing in the last decade. Pregnant women have a very challenging risk benefit trade-off in terms of ASM utilization, and it is crucial to know if increased utilization is seen among pregnant women. Objective: To examine time-trends of utilization of ASM therapies among pregnant women in Manitoba, Canada. Methods: We conducted a population-based cohort study using de-identified, linked administrative databases from Manitoba. Pregnancies between 1995 and 2018 were included. Four groups of pregnant people were created based on ASM exposure and epilepsy diagnosis. Results: Of 273,492 pregnancies, 812 (3/1000) had epilepsy diagnosis and were exposed to ASMs, 963 (3.5/1000) had epilepsy diagnosis and were unexposed, and 2742 (10/1000) were exposed to ASMs and did not have epilepsy diagnosis. Overall, the number of pregnancies exposed to ASMs increased significantly from 0.56% in 1997 to 2.21% in 2018 ( p < 0.0001). Subgroup analysis by epilepsy diagnosis showed no significant change in ASMs exposure among pregnant women with epilepsy [the proportion of women exposed to ASM from all pregnancies was 0.37% (in 1997) and 0.36% (in 2018), p = 0.24]. A drop in carbamazepine use was observed, while the number of lamotrigine prescriptions increased from 6.45% in 1997 to 52% by 2018. ASM use among pregnant women without epilepsy increased significantly from 0.19% in 1997 to 1.85% in 2018 ( p < 0.0001). In the total cohort of pregnancies, 1439 (0.53%) were exposed during their entire pregnancy, and 1369 (0.5%) were exposed only in their first trimester. Clonazepam was the most used ASM during the study period (1953 users, 0.71%), followed by gabapentin (785 users, 0.29%) and carbamazepine (449 users, 0.16%). Conclusion: No major shifts in the quantity of ASM use over the study period were observed among pregnant women with epilepsy. However, there was a significant increase in ASM use among pregnant women without epilepsy. The study results warrant further investigation into the implications of ASM use in pregnancy for indications other than epilepsy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shouman, Delaney, Kowalec, Ng, Ruth, Falk, Leong, Alessi-Severini, Lavu, Peymani and Eltonsy.)

Objective: To measure the incidence of long-term benzodiazepine receptor agonist (BZRA) use among individuals with anxiety, mood and/or sleep disorders. To identify factors associated with long-term use following the first prescription., Methods: This was a population-based retrospective cohort study using administrative databases in Manitoba, Canada. Individuals with anxiety/mood or sleep disorder who received their first BZRA between 1 April 2001 and 31 March 2015 were included. Long-term use was defined as ≥180 days. Logistic regression modelling was used to examine predictors of long-term use., Results: Among 206 933 individuals included, long-term BZRA use in the first episode of use was 4.5% (≥180 days) following their first prescription. Factors associated with ≥180 days of use included male sex (adjusted OR (aOR) 1.33, 95% CI 1.27 to 1.39), age ≥65 (aOR 5.15, 95% CI 4.81 to 5.52), income assistance (aOR 1.68, 95% CI 1.55 to 1.81), previous non-BZRA psychotropic (aOR 1.93, 95% CI 1.83 to 2.02) or opioid use (aOR 1.16, 95% CI 1.11 to 1.22), high comorbidity (aOR 1.43, 95% CI 1.32 to 1.55), high healthcare use (aOR 1.46, 95% CI 1.33 to 1.60) and psychiatrist prescriber (aOR 2.11, 95% CI 1.93 to 2.32)., Conclusions: Less than 1 in 20 patients use BZRAs ≥180 days in their first treatment episode. Several factors were associated with long-term use following the first prescription and further investigation into whether these factors need to be considered at the point of prescribing is warranted. In light of these findings, future research should examine the predictors of cumulative repeat episodes of BZRA exposure., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cardiovascular death is a common outcome in population-based studies about new healthcare interventions or treatments, such as new prescription medications. Vital statistics registration systems are often the preferred source of information about cause-specific mortality because they capture verified information about the deceased, but they may not always be accessible for linkage with other sources of population-based data. We assessed the validity of an algorithm applied to administrative health records for identifying cardiovascular deaths in population-based data., Methods: Administrative health records were from an existing multi-database cohort study about sodium-glucose cotransporter-2 (SGLT2) inhibitors, a new class of antidiabetic medications. Data were from 2013 to 2018 for five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, Quebec) and the United Kingdom (UK) Clinical Practice Research Datalink (CPRD). The cardiovascular mortality algorithm was based on in-hospital cardiovascular deaths identified from diagnosis codes and select out-of-hospital deaths. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated for the cardiovascular mortality algorithm using vital statistics registrations as the reference standard. Overall and stratified estimates and 95% confidence intervals (CIs) were computed; the latter were produced by site, location of death, sex, and age., Results: The cohort included 20,607 individuals (58.3% male; 77.2% ≥70 years). When compared to vital statistics registrations, the cardiovascular mortality algorithm had overall sensitivity of 64.8% (95% CI 63.6, 66.0); site-specific estimates ranged from 54.8 to 87.3%. Overall specificity was 74.9% (95% CI 74.1, 75.6) and overall PPV was 54.5% (95% CI 53.7, 55.3), while site-specific PPV ranged from 33.9 to 72.8%. The cardiovascular mortality algorithm had sensitivity of 57.1% (95% CI 55.4, 58.8) for in-hospital deaths and 72.3% (95% CI 70.8, 73.9) for out-of-hospital deaths; specificity was 88.8% (95% CI 88.1, 89.5) for in-hospital deaths and 58.5% (95% CI 57.3, 59.7) for out-of-hospital deaths., Conclusions: A cardiovascular mortality algorithm applied to administrative health records had moderate validity when compared to vital statistics data. Substantial variation existed across study sites representing different geographic locations and two healthcare systems. These variations may reflect different diagnostic coding practices and healthcare utilization patterns., (© 2021. The Author(s).)

Objective: Reports of amputations associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors have been inconsistent. We aimed to compare the risk of below-knee amputation with SGLT2 inhibitors versus dipeptidyl peptidase 4 (DPP-4) inhibitors among patients with type 2 diabetes., Research Design and Methods: This multicenter observational study used administrative health care databases from seven Canadian provinces and the U.K. Incident SGLT2 inhibitor users were matched to DPP-4 inhibitor users using a prevalent new-user design and time-conditional propensity scores. Cox proportional hazards models were used to estimate site-specific adjusted hazard ratios (HR) and corresponding 95% CIs of incident below-knee amputation for SGLT2 inhibitor versus DPP-4 inhibitor users. Random effects meta-analyses were used to pool the site-specific results., Results: The study cohort included 207,817 incident SGLT2 inhibitor users matched to 207,817 DPP-4 inhibitor users. During a mean exposed follow-up time of 11 months, the amputation rate was 1.3 per 1,000 person-years among SGLT2 inhibitor users and 1.5 per 1,000 person-years among DPP-4 inhibitor users. The adjusted HR of below-knee amputations associated with SGLT2 inhibitor use compared with DPP-4 inhibitor use was 0.88 (95% CI 0.71-1.09). Similar results were obtained in stratified analyses by specific SGLT2 inhibitor molecule., Conclusions: In this large multicenter observational study, there was no association between SGLT2 inhibitor use and incident below-knee amputations among patients with type 2 diabetes compared with DPP-4 inhibitor use. While these findings provide some reassurance, studies with a longer duration of follow-up are needed to assess potential long-term effects., (© 2020 by the American Diabetes Association.)

Background: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors could increase the risk for diabetic ketoacidosis (DKA)., Objective: To assess whether SGLT-2 inhibitors, compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, are associated with an increased risk for DKA in patients with type 2 diabetes., Design: Population-based cohort study; prevalent new-user design between 2013 and 2018. (ClinicalTrials.gov: NCT04017221)., Setting: Electronic health care databases from 7 Canadian provinces and the United Kingdom., Patients: 208 757 new users of SGLT-2 inhibitors were matched by using time-conditional propensity scores to 208 757 recipients of DPP-4 inhibitors., Measurements: Cox proportional hazards models estimated site-specific hazard ratios (HRs) with 95% CIs of DKA comparing receipt of SGLT-2 inhibitors with receipt of DPP-4 inhibitors, which were pooled by using random-effects models. Secondary analyses were stratified by molecule, age, sex, and prior receipt of insulin., Results: Overall, 521 patients were diagnosed with DKA during 370 454 person-years of follow-up (incidence rate per 1000 person-years, 1.40 [95% CI, 1.29 to 1.53]). Compared with DPP-4 inhibitors, SGLT-2 inhibitors were associated with an increased risk for DKA (incidence rate, 2.03 [CI, 1.83 to 2.25] versus 0.75 [CI, 0.63 to 0.89], respectively; HR, 2.85 [CI, 1.99 to 4.08]). Molecule-specific HRs were 1.86 (CI, 1.11 to 3.10) for dapagliflozin, 2.52 (CI, 1.23 to 5.14) for empagliflozin, and 3.58 (CI, 2.13 to 6.03) for canagliflozin. Age and sex did not modify the association; prior receipt of insulin appeared to decrease the risk., Limitations: There was unmeasured confounding and no laboratory data were available for the majority of patients, and molecule-specific analyses were conducted at a limited number of sites., Conclusion: SGLT-2 inhibitors were associated with an almost 3-fold increased risk for DKA, with molecule-specific analyses suggesting a class effect., Primary Funding Source: Canadian Institutes of Health Research.

Aim: To compare urosepsis rates in patients with type 2 diabetes treated using sodium-glucose co-transporter-2 inhibitors (SGLT2i) with dipeptidyl peptidase-4 inhibitors (DPP4i) in a real-world setting., Methods: We conducted a matched cohort study using a prevalent new-user design with time-conditional propensity scores. New users of SGLT2i from seven Canadian provinces and the UK were matched to DPP4i users. The primary outcome was hospitalization with a diagnosis of urosepsis and the secondary outcome was Fournier's gangrene. Site-specific hazard ratios for urosepsis comparing SGLT2i with DPP4i were estimated using Cox proportional hazards models and pooled using a random effects meta-analysis., Results: We included 208 244 users of SGLT2i and 208 244 users of DPP4i. Among SGLT2i users, 42% initiated canagliflozin, 31% dapagliflozin and 27% empagliflozin. During a mean follow-up of 0.9 years, patients initiating SGLT2i had a lower rate of urosepsis compared with those receiving DPP4i. The pooled adjusted hazard ratio was 0.58 (95% confidence interval [CI]: 0.42-0.80). The incidence rates of Fournier's gangrene were numerically similar in SGLT2i (0.08 per 1000 person-years; 95% CI: 0.05-0.13) and DPP4i users (0.14; 95% CI: 0.09-0.21)., Conclusions: In this large, multi-site study, we did not observe an increased risk for urosepsis associated with SGLT2i compared with DPP4i among patients with type 2 diabetes in a real-world setting., (© 2020 John Wiley & Sons Ltd.)

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., Competing Interests: Competing interests: Salaheddin Mahmud has received unrestricted research grants from Merck, GlaxoSmithKline, Sanofi Pasteur, Pfizer and Roche-Assurex for unrelated studies, and has also received fees as an advisory board member for Sanofi Pasteur. Silvia Alessi-Severini has received unrestricted research grants from Merck and Pfizer for unrelated studies. No other competing interests were declared., (© 2020 Joule Inc. or its licensors.)

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.

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: To estimate prevalence of continuous use (persistence) of prescribed cannabinoid medications for up to 1 year from initial prescription in Manitoba, Canada and predictors of duration of use., Design and Setting: A retrospective, population-based, cohort study using administrative data from the Manitoba Population Research Data Repository located at the Manitoba Centre for Health Policy, Canada., Participants: People without a record of a previous prescription who were prescribed a cannabinoid medication from 1 April 2004 to 1 April 2016 followed for 1 year from the date of first prescription., Measurements: Continuous prescribed cannabinoid medication use was defined as use without a gap exceeding 60 days between prescriptions. The primary outcome was prevalence of continuous prescribed cannabinoid medication use for up to 1 year. A secondary outcome was duration of continuous use. Predictors were socio-demographic characteristics, medical diagnoses and type of cannabinoid medication., Findings: Among 5452 new users, 18.1% [95% confidence interval (CI) = 17.08-19.12] were still using cannabinoids at 1 year. Median duration of use was 31 days [interquartile range (IQR) = 25-193]. This was highest for nabilone (33 days, IQR = 25-199) and lowest for nabiximols (20 days, IQR = 7-30). Use was longest among 19-45- and 46-64-year-old users and those with the highest socio-economic status. Fibromyalgia [hazard ratio (HR) = 0.89, 95% CI = 0.84-0.95], osteoarthritis (HR = 0.91, 95% CI = 0.82-0.97) and substance use disorder (HR = 0.85, 95% CI = 0.76-0.94) diagnoses were associated with longer use (HR for discontinuation-HR < 1 less discontinuation and longer use). A diagnosis of cancer was associated with shorter use (HR = 2.73, 95% CI = 2.02-3.67)., Conclusions: In Manitoba, Canada approximately 18% of people prescribed cannabinoid medication continue using for at least 1 year. Duration of use varies with type of cannabinoid medication, age, socio-economic status and dagnosis., (© 2019 Society for the Study of Addiction.)

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., Competing Interests: The authors have declared that no competing interests exist.

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.

Purpose: 1) To evaluate trends for benzodiazepines (BZD) and Z-Drugs over 15-years in a general Canadian adult population measured by: a) consumption b) pharmacologic exposure c) dose intensity and d) prevalence of use. 2) To demonstrate the utility of Diazepam Milligram Equivalence (DME) based measurements when used in conjunction with traditional standard measurements of drug utilization such as the Defined Daily Dose (DDD) system., Methods: Administrative data covering all prescriptions from April 2001-March 2016 for BZD and Z-Drugs for patients ≥18 years was used. Consumption was calculated as DDD/1000-person days. Dose intensity (DI) was determined by conversion of individual daily doses to Diazepam Milligram Equivalents (DME). Pharmacologic exposure (PE) was calculated as DME-DDD/1000-person days. Prevalence was determined as the proportion of the adult population with receipt of ≥1 prescription in a given year. Changes were assessed using either Poisson or simple linear regression at an alpha of 0.05., Results: Z-Drug usage (~99% zopiclone) statistically increased on every measure over the course of the study period; consumption (8.2 to 28.6 DDD/1000-person days), PE (4.1 to 14.3 DME-DDD/1000-person days), DI (5.0 to 5.43 DME/day) and prevalence (2.0% to 4.8%). For BZD the only statistically significant changes were in DI (17.1 to 20.1 DME/day) and prevalence (9.3% to 8.1%). Consumption and PE gradually increased from 2001 to 2011 for BZD before declining thus producing a non-significant trend for BZD., Conclusion: 1) Z-Drug usage increased markedly from 2001 to 2016 whereas BZD use only increased in terms of DI. 2) DME-based measurements enable further interpretation of BZD utilization compared to sole reliance on DDD.

Objective: To develop key performance indicators that evaluate the effectiveness of a prescription medication system., Methods: A modified RAND/UCLA appropriateness method was used to develop key performance indicators (KPIs) for a prescription medication system. A broad list of potential KPIs was compiled. A multidisciplinary group composed of 21 experts rated the potential KPIs. A face-to-face meeting was held following the first rating exercise to discuss each potential KPI individually. The expert panel undertook a final rating of KPIs. The final set of KPIs were those indicators where at least 80 percent of experts rated the indicator highly i.e. rating of ≥ 7 on a scale from 1 to 9., Results: 292 KPIs were identified from the published literature. After removing duplicates and combining similar indicators 71 KPIs were included. The final ranking resulted in six indicators being ranked 7 or higher by 80% of the respondents and an additional seven indicators being ranked 7 or higher by ≥70 but ≤80% of respondents. The six selected indicators include four specific disease areas, measure structural and process aspects of health service delivery, and assessed three of the domains of healthcare quality: efficiency, effectiveness, and safety., Conclusions: These indicators are recommended as a starting point to assess the current performance of prescription medication systems. Consideration should be given to developing indicators in additional disease areas as well as indicators that measure the domains of timeliness and patient-centeredness. Future work should focus on the feasibility of measuring these indicators., Competing Interests: The authors have declared that no competing interests exist.

Background: Pharmaceutically derived cannabinoids are used for several indications, particularly pain management. The extent of their use from a population perspective is unknown; hence, the aim of this study was to evaluate trends in pharmaceutical cannabinoid use in Manitoba., Methods: This was a retrospective population-based cross-sectional study using administrative data from the Manitoba Centre for Health Policy. Pharmaceutical cannabinoid users residing in Manitoba from Apr. 1, 2004, to Mar. 31, 2015 were identified. We assessed the annual prevalence and incidence of pharmaceutical cannabinoid use, and the sociodemographic characteristics and medical conditions of users., Results: We identified 5181 people who received at least 1 prescription for a pharmaceutical cannabinoid over the study period, 5033 of whom received their first prescription after Apr. 1, 2004. Nabilone accounted for 73 650 (96.0%) of all prescriptions dispensed; dronabinol was discontinued during the study period. The annual prevalence rate of use increased by 527.2%, from 21.5 (95% confidence interval [CI] 21.4-21.6) users per 100 000 people in 2004/05 to 134.9 (95% CI 134.7-135.1) users per 100 000 people in 2014/15. The annual incidence rate increased by 413.3%, from 12.1 (95% CI 12.1-12.2) users per 100 000 person-years in 2004/05 to 62.2 (95% CI 62.1-62.4) users per 100 000 person-years in 2014/15. The highest use was among older adults aged 46-64 years, females and urban area residents. One-third of incident users (1775 [35.3%]) had a diagnosis of fibromyalgia in a 2-year period before their first cannabinoid prescription. General practitioners initiated almost half (2350 [46.7%]) of first prescriptions, and anesthesiologists/pain specialists initiated one-quarter (1299 [25.8%])., Interpretation: The prevalence and incidence of pharmaceutical cannabinoid use increased over time. These findings provide insight into the use of cannabinoids before the introduction of recreational marijuana, which may affect this trend., Competing Interests: Competing interests: None declared., (Copyright 2018, Joule Inc. or its licensors.)

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.

Drug utilization research on benzodiazepines remains important for measuring trends in consumption within and across borders over time for the sake of monitoring prescribing patterns and identifying potential population safety concerns. The defined daily dose (DDD) system by the World Health Organization (WHO) remains the internationally accepted standard for measuring drug consumption; however, beyond consumption, DDD-based results are difficult to interpret when individual agents are compared with one another or are pooled into a total class-based estimate. The diazepam milligram equivalent (DME) system provides approximate conversions between benzodiazepines and Z-drugs (i.e. zopiclone, zolpidem, zaleplon) based on their pharmacologic potency. Despite this, conversion of total dispensed benzodiazepine quantities into DME values retains diazepam milligrams as the total unit of measurement, which is also impractical for population-level interpretation. In this paper, we propose the use of an integrated DME-DDD metric to obviate the limitations encountered when the component metrics are used in isolation. Through a case example, we demonstrate significant change in results between the DDD and DME-DDD method. Unlike the DDD method, the integrated DME-DDD metric offers estimation of population pharmacologic exposure, and enables superior interpretation of drug utilization results, especially for drug class summary reporting.

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.

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.

Objectives: To describe a cohort of young users of risperidone and quetiapine in the province of Manitoba (Canada) and assess the risk for movement disorders in the two treatments., Methods: This was a population-based study conducted on all residents of the province of 19 years of age and younger who received prescriptions for risperidone or quetiapine between April 1, 1996, and March 31, 2011. Incident rates of antipsychotic use were reported. The risk for movement disorders in patients treated with quetiapine compared with those treated with risperidone was assessed by time-to-event analysis using Cox proportional hazards models., Results: Between April 1, 1996, and March 31, 2011, 23,888 youth (age ≤19 years) were prescribed an antipsychotic agent. Among them, 8756 were identified as new incident users. After applying exclusion criteria, 2594 individuals comprised the cohort of users of risperidone and quetiapine. The use of quetiapine was associated with a lower risk of extrapyramidal symptoms (EPSs) adverse events. The unadjusted and adjusted hazard ratios (95% confidence interval [CI]) for quetiapine versus risperidone were 0.83 (0.56-1.25) and 0.53 (0.34-0.83), respectively., Conclusion: EPS diagnoses have been detected in children treated with quetiapine; however, the risk of movement disorders appears to be higher with treatment with risperidone. Clinicians should always take into consideration the risk-benefit before treating children with antipsychotic medications and should be vigilant of the onset of drug-induced adverse events.

Purpose: Pharmacy claims data is often used in pharmacoepidemiology studies, but no studies to date have examined whether it was possible to identify the use of blister packs in these databases. We aimed to determine whether medications dispensed in days divisible by 7 are more likely to be blister packed than medications dispensed in other quantities., Methods: Community pharmacies in Manitoba were invited to participate in a mail-out survey to identify the use of blister packaging for up to 25 patients who had a solid oral medication dispensed from April 1, 2012 to March 31, 2014. Eligible medications were identified using the population-based province-wide retail pharmacy network. Algorithms for identifying the use of blister packaging were determined by comparing the proportion of fills that confirmed blister pack use between different days supply quantities., Results: Twenty-seven out of 32 pharmacies that agreed to participate completed the survey. The total number of prescriptions in the analysis was 2045 of which 131 (6.4%) were dispensed in blister packaging. Overall, prescriptions dispensed in days divisible by 7 yielded a 72.5% sensitivity, 86.6% specificity, 30.3% PPV, and 97.9% NPV compared with prescriptions dispensed in other quantities. A 28-day to 30-day comparison yielded an 87.9% sensitivity, 96.1% specificity, 64.6% PPV, and 99.0% NPV., Conclusion: While the NPV was high, the PPV for identifying blister packaging using the days supply field in pharmacy claims data was modest given the low prevalence in blister pack use. The best predictor occurred when 28 days was compared with 30 days. KEY POINTS Blister packs are arranged in 4 × 7 compartments and are often used to improve adherence, but no studies have examined whether it was possible to identify the use of blister packs using the days supply field in pharmacy claims data. Findings show that a 28-day supply yielded a high sensitivity and specificity for identifying the use of blister packaging compared with a 30-day supply, but there is potential for misclassification. Future studies directed at examining subgroups that are more likely to use blister packs and replication of findings using other data sources in other jurisdictions are encouraged., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objectives: At 17.3%, smoking rates in Manitoba continue to exceed the national average. In this province, a total health care spending of more than $200 million per year has been attributed to smoking. This study examined the use of smoking cessation agents, including nicotine replacement products and prescription medications, in a sample of smokers in the city of Winnipeg., Methods: A simple multiple-choice questionnaire was administered to willing individuals attending 2 community pharmacies in Winnipeg, Manitoba. Data on demographics, smoking habits, previous attempts of smoking cessation and previous and current use of over-the-counter and prescription smoking cessation products were collected anonymously., Results: Of the 2237 individuals who were approached, 586 were smokers (26.2%) and 180 responded to the survey (30.7%); 48.9% were female. A majority of smokers (32.8%) reported smoking 16 to 25 cigarettes per day. More than 90% had smoked for more than 5 years, 27.2% had more than 5 previous quit attempts and 82.1% used smoking cessation products with the intention to quit. Self-motivation (44.4%) and family/friend advice (28.3%) were major reasons for quitting. Impact of health care practitioners' advice was low (6.4%). More than 80% of respondents reported that they had no insurance coverage for their smoking cessation products. Despite having the highest rate of use, both nicotine gum (33.3%) and patches (24.4%) were reported to have lower rates of perceived efficacy. Electronic cigarette (97.9%) and varenicline (70.6%) had the highest rates of reported effectiveness., Conclusion: Smokers wanting to quit undergo many attempts. Pharmacists should assume a key role in reaching out to smokers., Competing Interests: Declaration of Conflicting Interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Objective: To describe the extent of increase in use and the rate of continuation versus discontinuation of psychotropic agents before, during, and after pregnancy., Methods: Rates of psychotropic use (antidepressants, anxiolytic/sedative-hypnotics, antiepileptics, antipsychotics, lithium, stimulants) among women with a hospital-recorded pregnancy outcome were assessed using databases at the Manitoba Centre for Health Policy. Rate of use was defined as ≥1 prescription over the total number of pregnancies in the 3-12 months before pregnancy, 0-3 months before pregnancy, during pregnancy, or 3 months after pregnancy. Continued use was defined as ≥2 prescriptions with gap ≤14 days. Poisson regression was used to analyze trends., Results: Over the study period, a psychotropic drug was used before, during, or after pregnancy in 41,923 of 224,762 pregnancies. From 2001 to 2013, psychotropic use increased 1.5-fold from 11.1% to 16.2% ( p < 0.0001) in the 3-12 months before pregnancy, 1.6-fold from 6.4% to 10.5% ( p < 0.0001) in the 3 months before pregnancy, 1.8-fold from 3.3% to 6.0% ( p < 0.0001) during pregnancy, and 1.5-fold from 6.2% to 9.5% ( p < 0.0001) in the 3 months postpartum. Among the 13,579 women who received at least 1 psychotropic agent in the 3 months prior to pregnancy, 38.5% stopped the agent prior to pregnancy and only 10.3% continued use throughout pregnancy. Continued use throughout pregnancy was higher (56.9%) among the 6693 women who received at least 2 prescriptions for a psychotropic agent and were at least 80% adherent in the 3 months prior to pregnancy., Conclusion: The use of psychotropic agents increased over 12 years. The safety of continuing versus discontinuing these agents during pregnancy remains uncertain, but we observed a decrease in psychotropic drug use during the pregnancy period.

Objective: There has been much attention on appropriate prescribing in older adults in recent years. Recent guidelines favor the use of newer antidepressants over older agents based on their safety profile in this population. This study aimed to examine whether there has been a decline in older antidepressants and an increase in newer antidepressants used by older adults., Method: A retrospective cross-sectional study using administrative databases examined the annual incidence of antidepressant use (per 1000) of community-dwelling adults ≥60 years old between 1997/1998 and 2012/2013 in Manitoba, Canada., Results: The population of Manitoba ≥60 years increased by 25.6% from 188,296 to 236,569 from 1997/1998 to 2012/2013. New antidepressant use peaked to 45.9 per 1000 in 1999/2000, and then decreased steadily to 30.5 per 1000 in 2012/2013 (p < 0.0001). Incident amitriptyline use was high but declined from 15.5 to 7.4 per 1000 (p < 0.001). An increase in incident trazodone, mirtazapine, and venlafaxine use was observed (p < 0.001)., Conclusions: There has been an overall decrease in the annual incidence of antidepressant users in older adults over the last 16 years, with a marked decline in new amitriptyline use and an increase in the incidence of newer agents.

Background: Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are widely prescribed for mood and anxiety disorders. However, it is not clear whether SNRIs are more strongly associated with cardiovascular and cerebrovascular events than SSRIs., Methods: This was a propensity score-matched, population-based, cohort study of Manitobans who started an SSRI or SNRI between April 1, 1998, and March 31, 2014. The primary outcome was a composite of acute myocardial infarction (AMI), stroke, or cardiovascular-related hospitalization within 1 year of drug initiation. Each component of the primary outcome and death were analyzed separately in secondary analyses., Results: A total of 225,504 and 54,635 patients initiated treatment on an SSRI and SNRI, respectively. After propensity score matching, a higher risk was observed for the primary outcome among SNRI users (weighted hazards ratio [HR], 1.13; 95% confidence interval [CI], 1.06-1.21). Secondary analyses showed that the risk of nonfatal stroke was higher among SNRI users (weighted HR, 1.20; 95% CI, 1.08-1.33). The risk of death was higher among SNRI users without mood and/or anxiety disorders (weighted HR, 1.17; 95% CI; 1.03-1.32). No differences were observed in the risk of AMI or fatal stroke between SSRI and SNRI use., Conclusions: New SNRI use was associated with a higher risk of nonfatal stroke relative to SSRI use. Further investigation is warranted regarding the higher risk of death observed in our subgroup analysis among incident SNRI users without mood and/or anxiety disorders.

Background: Around 30% of the population will experience herpes zoster (HZ), 10% of whom develop postherpetic neuralgia (PHN). Together, these illnesses produce a significant economic burden to the healthcare system., Methods: Administrative healthcare data collected over the period of April 1 st 1997 to March 31 st 2014 were analyzed to determine the healthcare system burden of HZ using direct medical costs. Episodes of HZ were identified using international classification of disease (ICD) codes. Trends in age-adjusted (AA) HZ-rates were analyzed by piecewise-regression. Total annual and per-episode costs were determined for drug treatment, medical care, and hospitalizations within each year., Results: The incidence of HZ increased by 49.5% from 1997/98 to 2013/14. Piecewise-regression of AA-rates revealed a steady AA-rate of 4.7 episodes/1000 person-years (PY) from 1997/98 to a breakpoint in 2008/09, after which rates began to increase reaching 5.7 episodes/1000 PY in 2013/14. Drug costs rose significantly (p <0.03) from $89.77/episode (95% CI: $82.96, $96.59) to $127.34/episode (95% CI: $117.24, $137.44). Medical costs increased (p <0.0001) from $57.98/episode (95% CI; $55.26, $60.70) to $78.84/episode (95% CI; $74.08, $83.61). Hospitalization rates declined from 3.10% in 1997/98 to 1.36% in 2011/12, resulting in cost dropping from $397/episode (95% CI; $284, $511) to $195/episode (95% CI; $129, $260). Total annual costs of HZ and PHN were $1,997,183 in 2011/12, 4.7% lower than the 1997/98 costs of $2,095,633., Conclusion: A significant increase in annual number of HZ cases was observed, driven largely by demographic factors. A 21% increase in the AA-incidence reveals changes in HZ rates beyond those expected by population shifts. The large increase in incidence of HZ, with rising per episode medical and prescription costs were offset by dramatic drops in hospitalization rates, the net effect of which has been to hold the total costs relatively constant. However, the decrease in hospitalization rates slowed over the last half of the study, settling at 1.3% in the last 4 study years. The likely future of HZ burden is one of rising costs, primarily driven by the demographic shifts of an increasing and aging population.

Background: Community pharmacists frequently encounter patients at risk of medication misuse, diversion, and intentional overdose. However, few studies have examined the perspective of the pharmacist on the identification and management of these patients., Objective: To understand the perspective of community pharmacists on the dispensing of select medications commonly associated with misuse, diversion, and overdose., Methods: An online survey was disseminated by electronic mail to community pharmacists listed in the College of Pharmacists of Manitoba directory. The survey was open from July to September 2014. Descriptive statistics were used to describe demographic information of the pharmacist and practice setting, and pharmacists' perceptions on the dispensing of select medications., Results: A total of 82 community pharmacists completed the survey. Most pharmacists considered a one-month supply appropriate for a psychotropic agent; but a 7-10 day-supply was considered appropriate for an opioid for acute pain. Factors that aid pharmacist decisions on providing select medications to patients include familiarity with the patient, ease of access to medical history information, and ease of access to the prescribing physician. Only 10.3%, 16.2%, and 32.4% felt they have received adequate training on the management of patients at risk for suicide, drug diversion, and medication misuse, respectively., Conclusion: Findings from this study demonstrated a need for improved systems for managing patients at risk for medication misuse, diversion, and overdose. Strategies that warrant further attention for limiting the means of medication misuse include increased access to electronic medical records and providing additional continuing education support for community pharmacists.

Objective: "Antibenzodiazepine" campaigns have been conducted worldwide to limit the prescribing of these drugs because of concerns about inappropriate use and addiction. The causal relationship between long-term use and escalation to high doses has not been proven. This study assessed the extent of dose escalation among individuals who were long-term users of benzodiazepines or Z-hypnotics., Methods: A population-based study was conducted in the Canadian province of Manitoba using administrative health databases. Sustained use was defined as continuous use for at least two years (N=12,598). Dose escalation, measured in diazepam milligram equivalents (DMEs) per day and observed at six-month intervals, was assessed by using latent-class trajectory analysis. Characteristics of individuals with sustained use were described., Results: The analysis revealed four distinct groups. Two groups (<8% of the cohort) showed escalation to high doses (over 40 DMEs). More than 55% of high-dose escalators were in the 0- to 44-year age group, 75% lived in urban areas, and approximately 75% had a diagnosis of depression. Clonazepam was the drug most commonly involved with dose escalation; among individuals escalating to doses higher than 60 DMEs, 91% were using clonazepam. Rates of "doctor shopping" and "pharmacy hopping" were higher among younger adults, compared with older adults. Younger adults also had higher rates of concomitant antidepressant therapy., Conclusions: A limited segment of a population that received benzodiazepine prescriptions was classified as sustained users, and a small proportion of that group escalated to doses higher than those recommended by product monographs and clinical guidelines.

Background: Pain is a main symptom of herpes zoster (HZ), and postherpetic neuralgia (PHN) is a frequent complication occurring in 5% to 15% of cases, causing moderate to severe neuropathic pain. A population-based observational study was conducted to evaluate the treatment patterns and economic burden of prescription drug treatment of HZ and PHN pain in the province of Manitoba (Canada) over a period of 15 years., Methods: Administrative health care data, including medical and hospital separation records, were examined to identify episodes of HZ using International Classification of Diseases-9/10 codes between April 1, 1997 and March 31, 2014. Episodes of PHN were identified using medical and prescription claims. Incident use of analgesic, antidepressant, or anticonvulsant drugs was used to determine prescription pain costs., Results: The age-adjusted incidence of HZ increased from 4.7 episodes/1,000 person-years in 1997/98 to 5.7/1,000 person-years in 2013/14. PHN occurred in 9.2% of HZ cases, a rate that did not change over the study period (P=0.57). The annual cost to treat HZ pain rose by 174% from 1997/98, reaching CAD $332,981 in 2011/12, 82.8% (95% confidence interval [CI] 81.2%, 84.3%) of which was related to PHN. The per episode cost of HZ rose by 111% from $31.59 (95% CI $25.35, $37.84) to $66.81 (95% CI $56.84, $76.78) and by 94% for PHN from $292 (95% CI $225, $358) to $566 (95% CI $478, $655). These increases were driven by increasing use of anticonvulsants, primarily gabapentin, which accounted for 57% of the increase in cost., Conclusion: There has been an increase in the incidence of HZ and PHN and in the average cost associated with the prescription treatment of their resultant neuropathic pain. The primary driver of the increased episodic cost is the increased use of gabapentin. These changes have resulted in a substantial increase in the economic burden associated with HZ and PHN.

Background: Herpes zoster (HZ) is a common viral disease that produces a painful vesicular rash. Early use of antiviral medications is recommended, as it reduces pain and speeds healing. A population-based observational study was conducted to evaluate the changing burden of HZ in the province of Manitoba (Canada) over a period of 17 years., Methods: Administrative health care data including medical and hospital records were examined, and International Classification of Diseases, Ninth Revision, Clinical Modification and International Classification of Diseases, Tenth Revision, Clinical Modification codes were used to identify episodes of HZ between April 1, 1997 and March 31, 2014 in persons aged 20 or over. Annual age-adjusted incidence and hospitalization rates were calculated. Prescription records of HZ-diagnosed persons for acyclovir, valacyclovir, and famciclovir were used to calculate the rates and costs of antiviral treatment., Results: There were 73,893 identified cases of HZ and 1,245 HZ-related hospitalizations between 1997 and 2013. Of these episodes, 42,270 (57.2%) were treated with antiviral medications at a total cost of $4,708,065 (CAD). The age-adjusted incidence of HZ rose from 4.67/1,000 person years in 1997/1998 to 5.67/1,000 person years in 2013/2014, a 21.9% increase. Antiviral treatment rates increased from 41.7% to 66.2% of all diagnosed episodes. Mean treatment costs per episode dropped from $127.29 in 1997/1998 to $56.06 in 2013/2014, primarily due to the introduction of generic antiviral medications. The total cost of antiviral treatment peaked in 2005/2006 at $329,935 and dropped steadily thereafter to $223,973 in 2013/2014. HZ-related hospitalization rates decreased from 3.1% to 0.9%., Conclusion: While both the incidence of HZ and the rates of antiviral treatment have risen substantially, the economic burden from antiviral treatment has been decreasing since a peak in 2005/2006 and was only 3.2% higher in 2013/2014 than in 1997/1998. This drop in cost is attributed to the introduction of generic antiviral drugs.

Community pharmacists frequently encounter patients suspected to be at risk of medication misuse, divergence and overdose; yet, little research exists in describing how pharmacists effectively identify and intervene during these encounters. This study aimed to understand the barriers and facilitators in community pharmacy practice using a focus group design to help inform policymakers in the development of effective and feasible strategies for limiting the means of medication misuse. Findings revealed three themes: (1) patient-level barriers (deciphering signs of misuse); (2) pharmacist-level barriers (type of practice experience); and (3) system-level barriers (prescriber, third-party payer). Insight into pharmacy practice provided a foundation for future study to explore strategies for improving care for at-risk patients.