National and interprovincial prescribing patterns of JAK-inhibitors in Canada: a repeated cross-sectional analysis.

Janus Kinase (JAK) inhibitors have emerged as a novel category of medications to treat a variety of immune-mediated conditions. However, limited insight exists regarding the impact of safety concerns on their usage and prescribing practices. Therefore, the objective of this study was to describe the utilization of JAK-inhibitors in Canada, both nationally and within individual provinces. We used data from IQVIA's Compuscript database. We conducted a repeated cross-sectional study of all JAK-inhibitor units dispensed in retail pharmacies (tofacitinib, ruxolitinib, baricitinib, and upadacitinib) within the ten Canadian provinces from July 1, 2016, to June 30, 2022. Throughout Canada, outpatient pharmacies dispensed an estimated total of 26,126,409 JAK-inhibitor units between 2016 and 2022, averaging 9,431 units dispensed per 100,000 population. All provinces had increasing rates of JAK-inhibitor units dispensed over time, whereby between July 2021 to June 2022, New Brunswick exhibited the highest rates (27,696 units per 100,000), and Prince Edward Island demonstrated the lowest rates (10,065 units per 100,000). In this study, utilization of JAK-inhibitors increased in Canada over the study period, evident at both provincial and national levels. Variability in JAK-inhibitor utilization between provinces underscores the necessity for further investigations to ascertain appropriate usage practices. Key Points • From 2016 to 2022, an estimated total of 26,126,409 JAK-inhibitor units were dispensed in retail pharmacies across Canada, with an average rate of 9,431 units dispensed for every 100,000 people in the population. • Tofacitinib was the most dispensed JAK-inhibitor during the entire study period, making up 76% of all units dispensed. Ruxolitinib, upadacitinib, and baricitinib made up 16%, 7.9%, and 1.1% of the JAK-inhibitor units dispensed, respectively. • The variance in provincial adoption of JAK-inhibitors across Canada might be influenced by several factors, including drug coverage availability, disease prevalence, and physician prescribing patterns.

Canadian trends in spending on liver hospitalizations and transplants: 2004-2020.

Background: The incidence and prevalence of liver disease are increasing and contribute to significant morbidity and mortality. In Canada, more than 3 million people live with liver diseases, accounting for approximately 2% of all hospitalizations. However, it remains unclear how much liver hospitalizations cost the Canadian health care system. Thus, this study estimates the cost of liver-related hospitalization across Canada. Methods: We conducted a population-based, retrospective study using acute inpatient admission data for liver-related hospitalizations obtained from the Canadian Institute for Health Information. We calculated the total and the average nominal spending for liver hospitalizations nationally from April 1, 2004, to March 31, 2020, based on fiscal year (FY). In addition, we stratified the average liver hospitalization spending based on age and sex group. Results: Canada spent $947 million on liver-related hospitalizations in FY2019, a 145% growth in spending from FY2004. The average liver disease-related hospitalization was estimated to be $17,506 in FY2019. Within the sub-group analysis, the age group <30 showed the highest average cost per hospitalization at $21,776; however, there was no significant difference in cost between males and females. Across the different provinces in FY2019, Alberta experienced the highest average spending per hospitalization at $23,150, whereas Ontario had the lowest spending at $15,712. Conclusions: Liver-related hospitalizations are associated with high spending that is increasing nationally with variations across provinces and territories. Our results are of great use for economic evaluations of novel interventions in the future.

Comparison of Healthcare Utilization Between Telemedicine and Standard Care: A Propensity-Score Matched Cohort Study Among Individuals With Chronic Psychotic Disorders in Ontario, Canada.

Background: Telemedicine adoption has grown significantly due to the coronavirus of 2019 pandemic; however, it remains unclear what the impact of widespread telemedicine use is on healthcare utilization among individuals with psychosis. Objectives: To investigate the impact of telemedicine use on changes in healthcare utilization among patients with chronic psychotic disorders (CPDs). Study Design: We conducted a population-based, retrospective propensity-matched cohort study using healthcare administrative data in Ontario, Canada. Patients were included if they had at least one ambulatory visit between March 14, 2020 and September 30, 2020 and a CPD diagnosis any time before March 14, 2020. Telemedicine users (2+ virtual visits after March 14, 2020) were propensity score-matched 1:1 with standard care users (minimum of 1 in-person or virtual ambulatory visit and maximum of 1 virtual visit after March 14, 2020) based on several baseline characteristics. Monthly use of various healthcare services was compared between the two groups from 12 months before to 3 months after their index in-person or virtual ambulatory visit after March 14, 2020 using generalized estimating equations (eg, hospitalizations, emergency department [ED] visits, and outpatient physician visits). The slope of change over the study period (ie, rate ratio) as well as a ratio of slopes, were calculated for both telemedicine and standard care groups for each outcome. Study Results: A total of 18 333 pairs of telemedicine and standard care patients were identified after matching (60.8% male, mean [SD] age 45.4 [16.3] years). There was a significantly greater decline across time in the telemedicine group compared to the standard care group for ED visits due to any psychiatric conditions (ratio of slopes for telemedicine vs standard care (95% CI), 0.98 (0.98 to 0.99)). However, declines in primary care visit rates (ratio of slopes for telemedicine vs standard care (1.01 (1.01 to 1.02)), mental health outpatient visits with primary care (1.03 (1.03 to 1.04)), and all-cause outpatient visits with primary care (1.01 (1.01 to 1.02)), were steeper among the standard care group than telemedicine group. Conclusions: Overall, patients with CPDs appeared to benefit from telemedicine as evidenced by increased outpatient healthcare utilization and reductions in ED visits due to psychiatric conditions. This suggests that telemedicine may have allowed this patient group to have better access and continuity of care during the initial waves of the pandemic.

The Association Between Telemedicine Use and Changes in Health Care Usage and Outcomes in Patients With Congestive Heart Failure: Retrospective Cohort Study.

BACKGROUND: Telemedicine use has become widespread owing to the COVID-19 pandemic, but its impact on patient outcomes remains unclear. OBJECTIVE: We sought to investigate the effect of telemedicine use on changes in health care usage and clinical outcomes in patients diagnosed with congestive heart failure (CHF). METHODS: We conducted a population-based retrospective cohort study using administrative data in Ontario, Canada. Patients were included if they had at least one ambulatory visit between March 14 and September 30, 2020, and a heart failure diagnosis any time prior to March 14, 2020. Telemedicine users were propensity score-matched with unexposed users based on several baseline characteristics. Monthly use of various health care services was compared between the 2 groups during 12 months before to 3 months after their index in-person or telemedicine ambulatory visit after March 14, 2020, using generalized estimating equations. RESULTS: A total of 11,131 pairs of telemedicine and unexposed patients were identified after matching (49% male; mean age 78.9, SD 12.0 years). All patients showed significant reductions in health service usage from pre- to postindex visit. There was a greater decline across time in the unexposed group than in the telemedicine group for CHF admissions (ratio of slopes for high- vs low-frequency users 1.02, 95% CI 1.02-1.03), cardiovascular admissions (1.03, 95% CI 1.02-1.04), any-cause admissions (1.03, 95% CI 1.02-1.04), any-cause ED visits (1.03, 95% CI 1.03-1.04), visits with any cardiologist (1.01, 95% CI 1.01-1.02), laboratory tests (1.02, 95% CI 1.02-1.03), diagnostic tests (1.04, 95% CI 1.03-1.05), and new prescriptions (1.02, 95% CI 1.01-1.03). However, the decline in primary care visit rates was steeper among telemedicine patients than among unexposed patients (ratio of slopes 0.99, 95% CI 0.99-1.00). CONCLUSIONS: Overall health care usage over time appeared higher among telemedicine users than among low-frequency users or nonusers, suggesting that telemedicine was used by patients with the greatest need or that it allowed patients to have better access or continuity of care among those who received it.

Virtual care use during the COVID-19 pandemic and its impact on healthcare utilization in patients with chronic disease: A population-based repeated cross-sectional study.

PURPOSE: It is currently unclear how the shift towards virtual care during the 2019 novel coronavirus (COVID-19) pandemic may have impacted chronic disease management at a population level. The goals of our study were to provide a description of the levels of use of virtual care services relative to in-person care in patients with chronic disease across Ontario, Canada and to describe levels of healthcare utilization in low versus high virtual care users. METHODS: We used linked health administrative data to conduct a population-based, repeated cross-sectional study of all ambulatory patient visits in Ontario, Canada (January 1, 2018 to January 16, 2021). Further stratifications were also completed to examine patients with COPD, heart failure, asthma, hypertension, diabetes, mental illness, and angina. Patients were classified as low (max 1 virtual care visit) vs. high virtual care users. A time-series analysis was done using interventional autoregressive integrated moving average (ARIMA) modelling on weekly hospitalizations, outpatient visits, and diagnostic tests. RESULTS: The use of virtual care increased across all chronic disease patient populations. Virtual care constituted at least half of the total care in all conditions. Both low and high virtual care user groups experienced a statistically significant reduction in hospitalizations and laboratory testing at the start of the pandemic. Hospitalization volumes increased again only among the high users, while testing increased in both groups. Outpatient visits among high users remained unaffected by the pandemic but dropped in low users. CONCLUSION: The decrease of in-person care during the pandemic was accompanied by an increase in virtual care, which ultimately allowed patients with chronic disease to return to the same visit rate as they had before the onset of the pandemic. Virtual care was adopted across various chronic conditions, but the relative adoption of virtual care varied by condition with highest rates seen in mental health.

Regional differences in access to direct-acting antiviral treatments for hepatitis C across Ontario: A cross-sectional study.

Background: Direct-acting antivirals (DAAs) are curative treatments for hepatitis C virus (HCV) infection, a condition affecting over 100,000 Ontarians. Although DAAs are covered under the public drug programs in Ontario, receiving prescriptions depends on access to healthcare. The aim of this study is to understand the relationship between DAA treatment rates and distance to prescriber in Ontario, Canada. Methods: We conducted a cross-sectional study and identified patients who filled a DAA prescription through the Ontario Drug Benefit (ODB) in 2019. We calculated crude (per 100,000 ODB recipients) and adjusted (by a regional HCV infection rate) DAA treatment rates by public health unit (PHU). We reported median distances to provider for all visit types, in-person visits, virtual visits, and proportions of visits that were virtual. Results: In 2019, the crude DAA treatment rate for Ontario is 83.0 patients per 100,000 ODB recipients. The HCV-adjusted DAA treatment rate ranges from 28.2 (Northwestern Ontario) to 188.5 (Eastern Ontario) per 100,000. In our primary analysis, patients in rural PHUs, including Northwestern and Porcupine, were among the highest median distances to prescriber for all visit types (1,195 km and 556 km, respectively). These PHUs also had the highest proportions of virtual visits (greater than 60%). Urban PHUs, such as Toronto and Ottawa, had smaller median distances for all visit types, with smaller proportions of virtual visits (10.8% and 12.4%, respectively). Conclusion: We observed heterogeneity in treatment rates, distance to DAA prescribers and use of virtual care in the management of HCV. Increasing use of telemedicine in regions with limited utilization of DAAs may improve access.

Evaluation of field-in-field, three-field, and four-field techniques for treatment planning of radiotherapy of pancreatic cancer.

Background: Pancreatic adenocarcinoma is a lethal condition with poor outcomes by various treatment modalities and an increasing incidence. Aim: The aim of this study is to evaluate the advantages of field-in-field (FIF) versus three-field and four-field radiation treatment planning techniques in three-dimensional treatment of patients with pancreatic cancer. Materials and Methods: The evaluations of these planning techniques were performed in terms of physical and biological criteria. Radiotherapy treatment data of 20 patients with pancreatic cancer were selected and evaluated for FIF, three-field, and four-field treatment techniques. The patients were treated by 6 MV photon beam of a medical linac, and these three treatment planning techniques were evaluated for all the 20 patients. The plans were compared based on dose distribution in the target volume, monitor unit (MU), and dose to organs at risk (OARs). Results: The results have shown that, with assuming the same prescribed dose to planned target volume, FIF plans have some advantages over three-field and four-field treatment plans, based on MU values, V20 Gy in the right lung, V20 Gy in the left lung, Dmean in the left kidney, Dmean in the liver, and Dmean in the spinal cord. Based on the obtained results, the use of FIF technique reduces MUs compared to the three-field and four-field techniques. Conclusion: Having a less MU for performing treatment reduces scattered radiation and therefore reduces the risk of secondary cancer in normal tissues. In addition, the use of FIF technique has advantage of less radiation dose to some OARs.

Childhood trauma exposure and personality traits in schizophrenia patients.

Childhood trauma in schizophrenia (SCZ) is associated with aberrant neurobiological downstream effects and cognitive deficits that markedly hinder patient outcome and functioning. However, the relationship between specific forms of childhood abuse and the tendency for certain personality traits in patients with SCZ has not been comprehensively studied yet. We recruited 374 SCZ patients and screened for history of physical abuse (PA), emotional abuse (EA), sexual abuse (SA), physical neglect (PN) and emotional neglect (EN) using the Childhood Trauma Questionnaire and measured personality traits using the NEO Five-Factor inventory. Using CTQ cut-off scores, the prevalence of EA, PA, SA, EN and PN was 60.7%, 42.0%, 37.7%, 64.2% and 54.3% respectively. Exposure to any form of childhood abuse was associated with increased neuroticism. Exposure to EA, SA, PN and EN was correlated with decreased agreeableness and conscientiousness scores. PN, EN and PA exposure was associated with decreased openness while EA, PN and EN exposure was associated with decreased extraversion. Furthermore, a positive correlation was found between all forms of childhood abuse and trait neuroticism whereas negative correlations were found between certain forms of childhood abuse and all other personality traits. Exposure to specific forms of childhood abuse was associated with specific personality traits in patients with SCZ.

Head-to-head comparison of various antipsychotic agents on genome-wide methylation in schizophrenia.

Aim: To explore possible differences in genome-wide methylation between schizophrenia patients who consume various antipsychotics. Methods: We compared DNA methylation in leukocytes between the following cohorts: clozapine (n = 19) versus risperidone (n = 19), clozapine (n = 12) versus olanzapine (n = 12), clozapine (n = 9) versus quetiapine (n = 9) and clozapine (n = 33) versus healthy controls (n = 33). Subjects were matched for age, sex, ethnicity, smoking status and leukocyte proportions. Results: No single CpG site reached genome-wide significance for clozapine versus risperidone/olanzapine/quetiapine. For clozapine versus quetiapine, one significantly differentially methylated region was found - ch5: 176797920-176798049 (fwer = 0.075). Clozapine versus healthy controls yielded thousands of significantly differentially methylated CpG sites. Conclusions: Establishing antipsychotic induced genome-wide methylation patterns will further elucidate the biological and clinical effects of antipsychotic administration.

Assessment of Stimulant Use and Cardiovascular Event Risks Among Older Adults.

Importance: Use of stimulants continues to increase among older adults for a variety of indications. An association between stimulant use and increased risk of cardiovascular (CV) events has been established among children and young adults, but few studies have explored the risk of CV events among older patients, a group with increased baseline risk. Objective: To evaluate the association between stimulant use and risk of CV events among older adults. Design, Setting, and Participants: This propensity score-matched cohort study, with 4 nonusers per 1 user, was conducted from July 1, 2017, to June 27, 2019, using data from population-based health care databases from Ontario, Canada, from January 1, 2002, to December 31, 2016. Included individuals were outpatients aged 66 years or older. Exposures: Initiation of a prescription stimulant. Main Outcomes and Measures: The primary outcome was a CV event, defined as a composite of emergency department visit or hospitalization for myocardial infarction, stroke or transient ischemic attack (TIA), or ventricular arrhythmia. Risk of CV event was assessed at 30 days, 180 days, and 365 days after initiation of stimulants from Cox proportional hazard models. A secondary analysis assessed each component of the primary outcome separately. Results: Among 6457 older adults who initiated a prescription stimulant (ie, the exposed group) and 24 853 older adults who did not initiate such treatment (ie, the unexposed group), the distribution of baseline patient characteristics was well balanced after matching (sex: 3173 [49.1%] men vs 12 112 [48.7%] men; standardized difference, 0.01; median [IQR] age: 74 [69-80] years vs 74 [69-80] years; standardized difference, 0.01). Within this cohort, there were 932 CV events during the 365-day follow-up (5.11 events per 100 person-years among individuals who initiated stimulants). In the primary analysis, stimulant initiation was associated with increased risk of CV events at 30 days (hazard ratio [HR], 1.4; 95% CI, 1.1-1.8) but not at 180 days (HR, 1.2; 95% CI, 0.9-1.6) or 365 days (HR, 1.0; 95% CI, 0.6 to 1.8). In the secondary analysis, stimulant initiation was associated with increased risk of ventricular arrhythmias (HR, 3.0; 95% CI, 1.1-8.7) and stroke or TIA (HR, 1.6; 95% CI, 1.1-2.1) at 30 days. Conclusions and Relevance: This cohort study found that stimulant use was associated with an early increase in CV events among older adults with no association for long-term use.

Impact of COVID-19 on Prescribing Trends of Direct-Acting Antivirals for the Treatment of Hepatitis C in Ontario, Canada.

INTRODUCTION: Direct-acting antivirals (DAAs) are curative treatments for hepatitis C. However, initiation of these treatments requires adequate healthcare access. Coronavirus 2019 (COVID-19) resulted in restrictions to healthcare services in March 2020. We examined the impact of COVID-19 on the number of individuals dispensed DAAs. METHODS: This is a cross-sectional study examining the number of individuals dispensed DAAs in Ontario, Canada, from 2018 to 2020. Time-series models determined the impact of healthcare restrictions on DAA dispensations. RESULTS: Healthcare restrictions resulted in a 49.3% decrease in DAA dispensations (P = 0.026). DISCUSSION: COVID-19-related healthcare restrictions significantly affected access to DAAs. Studies exploring the long-term effects on reduced treatment are needed.

Global Utilization Trends of Direct Acting Antivirals (DAAs) during the COVID-19 Pandemic: A Time Series Analysis.

The 2019 novel coronavirus (COVID-19) pandemic has placed a significant strain on hepatitis programs and interventions (screening, diagnosis, and treatment) at a critical moment in the context of hepatitis C virus (HCV) elimination. We sought to quantify changes in Direct Acting Antiviral (DAA) utilization among different countries during the pandemic. We conducted a cross-sectional time series analysis between 1 September 2018 and 31 August 2020, using the IQVIA MIDAS database, which contains DAA purchase data for 54 countries. We examined the percent change in DAA units dispensed (e.g., pills and capsules) from March to August 2019 to the same period of time in 2020 across the 54 countries. Interrupted time-series analysis was used to examine the impact of COVID-19 on monthly rates of DAA utilization across each of the major developed economies (G7 nations). Overall, 46 of 54 (85%) jurisdictions experienced a decline in DAA utilization during the pandemic, with an average of -43% (range: -1% in Finland to -93% in Brazil). All high HCV prevalence (HCV prevalence > 2%) countries in the database experienced a decline in utilization, average -49% (range: -17% in Kazakhstan to -90% in Egypt). Across the G7 nations, we also observed a decreased trend in DAA utilization during the early months of the pandemic, with significant declines (p < 0.01) for Canada, Germany, the United Kingdom, and the United States of America. The global response to COVID-19 led to a large decrease in DAA utilization globally. Deliberate efforts to counteract the impact of COVID-19 on treatment delivery are needed to support the goal of HCV elimination.

New-generation antiepileptic drugs during pregnancy and the risk of attention-deficit hyperactivity disorder: A scoping review.

The use of maternal antiepileptic drug (AED) during pregnancy is associated with an increased risk of cognitive adverse effects among the offspring. As new-generation AEDs continue to enter the market, evidence on their safety during pregnancy is limited yet necessary. To date, there are no published reviews summarizing the evidence of new-generation AED exposure in utero and the development of attention deficit-hyperactivity disorder (ADHD) in the offspring. The objective of this scoping review is to summarize the available evidence on the risk of ADHD after maternal exposure to new-generation AEDs during pregnancy. We searched EMBASE and MEDLINE for articles published from January 1988 to April 2020. New-generation AEDs were considered if marketed after 1988. ADHD was defined as attention-deficit hyperactivity disorder, hyperkinetic disorder, hyperkinesis, or conduct disorder. Of the total articles screened (n = 805), eight publications were finally included (seven cohort studies and one systematic review). Across the studies, the sample size of pregnant women exposed to AEDs ranged from 1 to 1383. Monotherapy was examined in six studies (mostly lamotrigine), while only two studies examined polytherapy. The included studies reported a range of adjusted relative risks, from 0.84 [0.59-1.19] to 1.63 [0.41-6.06]. Lamotrigine monotherapy holds the largest body of evidence, concluding that no significant risk of ADHD exists among the offspring. However, the available evidence is considered scarce and has several methodological limitations. Disentangling the effect of AEDs from epilepsy itself and examining polytherapies are challenges that merit additional investigations. Further comparative safety studies with longer follow-up periods and large sample sizes are needed to accurately quantify the true impact of new-generation AED exposure during pregnancy and ADHD in children.

Spending on Hepatitis C Antivirals in the United States and Canada, 2014 to 2018.

OBJECTIVES: Hepatitis C virus (HCV) antivirals have been shown to be highly effective with minimal adverse effects, but they are costly. Little is known about the national spending on this drug class in either Canada or the United States, 2 countries with different drug pricing regulations. Thus the objective of this study was to compare drug expenditure on HCV medications in the United States and Canada. METHODS: This was a retrospective cross-sectional study using the IQVIA National Sales Perspectives (United States) and Geographic Prescription Monitor (Canada) databases, which contains prescription transactions from American and Canadian pharmacies. All prescription claims for the period between January 1, 2014, and June 30, 2018, were used to describe HCV antiviral expenditure in both countries. RESULTS: The United States and Canada spent $59.7 billion and $2.8 billion on HCV medications, respectively. Population-adjusted HCV medication costs were higher in the United States ($1 million per 100 000 population) compared with Canada ($0.4 million per 100 000 population). CONCLUSIONS: Although the rates of HCV infection are similar in the 2 countries, these findings highlight the differences in both the reimbursement utilization policy for HCV treatments in the countries and the major differences in drug pricing policies. As policies to reduce drug spending in the United States are explored, this article highlights the potential cost implications of implementing Canadian index pricing.

Evaluation of lung heterogeneity effects on dosimetric parameters in small photon fields using MAGIC polymer gel, Gafchromic film, and Monte Carlo simulation.

In this work, the performance of MAGIC polymer gel in measuring dosimetric parameters beyond lung heterogeneity in small fields was investigated. All data were obtained using MAGIC, EBT2, and MC in four small field sizes. The maximum local differences between MAGIC and MC were less than 5.1, 3.9, 3.1, and 2.6% for PDD values behind lung heterogeneity at 5, 10, 20, and 30 mm field sizes, respectively. The findings showed that MAGIC is a suitable tool for dosimetry behind low-density heterogeneity.