Provincial Drug Research Articles

Cluster B personality disorders and psychotropic medications: a focused analysis of trends and patterns across sex and age groups.

This study investigated sex and age differences in patterns of psychotropic medication use before and after the initial diagnosis of Cluster B personality disorders (PDs) and analyzed trends over time. Analyzing data from the Quebec Integrated Chronic Disease Surveillance System for individuals newly diagnosed with Cluster B PD (≥ 14 years) between 2002 and 2018 and under the provincial public drug plan, we calculated yearly and monthly proportions of individuals exposed to psychotropic medications during the year before and after their diagnosis by sex and age. Robust Poisson regression models assessed the association between sex and exposure to psychotropic medications after the diagnosis of Cluster B PD. Among 87,778 individuals with a first Cluster B PD diagnosis (mean age: 44.5 years; 57.5% women), the proportion of users increased post-diagnosis. Notably, after diagnosis, females were more likely to receive psychiatric medications (between 78.9% and 83.7% during the study period vs. 72.8% and 76.8%). Males were less likely than females to receive antidepressants (adjusted prevalence ratio (aPR): 0.83; 99% confidence interval (CI): 0.82-0.85) and anxiolytics (aPR: 0.86; 99%CI: 0.84-0.88), whereas they had higher exposure to antipsychotics (aPR: 1.04; 99%CI: 1.02-1.06) and ADHD medications (aPR: 1.14; 99%CI: 1.07-1.2). Age-specific trends showed increased ADHD medication use among younger patients (14-24 years), and anxiolytic use predominated in those aged ≥ 65 years. Psychotropic medication use was high among Cluster B PD patients, with differences in medication classes according to age and sex. The marked sex and age differences in psychotropic medication use among Cluster B PD patients underscore the need for a sex-sensitive and age-specific approach in psychiatric care.

Experimental study on H2O2 activation of HSC-T6 and hepatic fibrosis in cholestatic mice by "Yajieshaba"

Ethnopharmacological relevanceYajieshaba (YJSB), approved by the Yunnan Provincial Food and Drug Administration in 2008, are known for their anti-inflammatory, antiviral, and pro-apoptotic properties, effectively treating Hepatic fibrosis (HF). However, its mechanism of action remains unclear. Aim of the studyThe objective of this investigation is to explore how YJSB influences the TGF-β1/Smad signaling pathway as a strategy for reducing HF. MethodsThe establishment of a HF model in mice involved ligation of the common bile duct, followed by administration of YJSB. Body and liver weights were measured, and the liver index calculated. Serum levels of ALT, AST, ALP, TBA, and TBIL were assessed using colorimetric methods. Additionally, liver homogenates were analyzed for PIIINP, Col-IV, LN, HA, and Hyp, as well as TGF-β1 activity, using ELISA. Histological analyses of liver sections, stained with H&E, Ag, and Masson's trichrome, were performed to examine inflammation and the accumulation of collagen and reticular fibers. These studies aimed to elucidate the pharmacodynamic effects of YJSB on HF in mice with bile duct obstruction. The target pathways of YJSB were preliminarily identified through immunofluorescence detection of TGF-β1, P-Smad2L, P-Smad2C, P-Smad3L, P-Smad3C, and Smad4 proteins. In vitro experiments included the induction of hepatic stellate cell (HSC-T6) activation by H2O2. A cell injury model was established for HSC-T6, and the CCK-8 assay was used to determine the optimal YJSB concentration and treatment duration. After pirfenidone (PFD) administration, which inhibits the TGF-β1/Smad pathway, the effects of YJSB on HSC-T6 cell proliferation were observed. ELISA assays quantified Col-III, α-SMA, and Col-I in cell lysates to assess YJSB's impact on collagen synthesis in HSC-T6 cells. Western blot analysis was performed to assess the protein levels within the TGF-β1/Smad signaling cascade. ResultsIn the HF mouse model, administration of YJSB notably augmented the body weight and reduced the liver index. Concurrently, there was an elevation in serum concentrations of ALP, AST, ALT, TBA, and TBIL. Similarly, in the liver homogenates of HF mice, increases were observed in the levels of HA, PIIINP, Col-IV, LN, Hyp, and TGF-β1. Histological assessments using H&E, Ag, and Masson stains indicated a substantial diminution in liver tissue damage. Through immunofluorescence analysis, it was discerned that YJSB modulated the expression of TGF-β1, P-Smad2L, P-Smad2C, and P-Smad3L downwards, while elevating P-Smad3C and Smad4 protein expressions. Additional investigations revealed a significant reduction in α-SMA, Col-I, and Col-III levels in cell culture fluids, suggesting a decrease in collagen synthesis and a protective role against cellular damage. Western blot analyses demonstrated that the TGF-β1/Smad pathway inhibitor, PFD, acted in synergy with YJSB, enhancing its regulatory effects on this pathway, decreasing levels of TGF-β1, P-Smad2L, P-Smad2C, P-Smad3L, and promoting the expression of P-Smad3C. ConclusionsYJSB demonstrates a pharmacodynamic effect against HF, enhancing liver functionality and effectively mitigating the damage associated with bile duct obstruction. The proposed action mechanism of YJSB involves modulation of the TGF-β1/Smad signaling pathway. Research indicates that YJSB might play a role in suppressing the movement, programmed cell death, and activation of HSC-T6, potentially decelerating the advancement of hepatic fibrosis.

The Association of Adverse Pregnancy Outcomes With Overactive Bladder Anticholinergics.

The pregnancy safety and teratogenicity of overactive bladder (OAB) anticholinergic medications in humans are unknown. The aim of this study was to determine if the use of OAB anticholinergics during pregnancy was associated with adverse pregnancy outcomes or congenital malformation. Using routinely collected health care data from Ontario, Canada, we conducted a retrospective cohort study and identified women aged 18-45 years who gave birth between 2004 and 2022 and were eligible for provincial drug benefits. We used gestational age and birth dates to approximate conception dates. The primary exposure was filling a prescription for an OAB anticholinergic during pregnancy (compared with nonusers). The coprimary outcomes were pregnancy complication (which included preterm birth or low birth weight) and congenital malformation. Poisson regression models with generalized estimating equations and inverse probability of treatment weighting were used to estimate risk ratios (RRs). We identified 138,271 births, of which 479 (0.3%) had exposure to an OAB anticholinergic, for a median of 60 (interquartile range, 30-120) days. The most common OAB anticholinergic was oxybutynin (84%). In the weighted cohort, the risk of a pregnancy complication was significantly elevated (RR, 1.65; 95% confidence interval [CI], 1.40-1.95; P < 0.01; absolute risk difference + 9.9% [95% CI, +5.9, +13.9]), with a dose-response relationship close to statistical significance (P = 0.07). The risk of congenital malformations with OAB anticholinergic use was not significant (RR, 1.24; 95% CI, 0.85-1.80; P = 0.26). Pregnant women who take OAB anticholinergic medications have a higher risk of pregnancy complications, but not congenital malformations, compared with non-OAB anticholinergic users. This information can be used when counseling women of child-bearing age about these medications.

Perception of pneumocystis jirovecii pneumonia (PJP) prophylaxis in glioma patients receiving concurrent temozolomide and radiation- a patient and physician survey.

Pneumocystis jirovecii pneumonia (PJP) prophylaxis is required by provincial and national drug monographs during glioma treatment using temozolomide (TMZ) concurrently with radiation (TMZ-RT). However, real-world data suggest the potential benefits of PJP prophylaxis may not outweigh its potential harms in this population. We conducted a single-center patient survey and a national physician survey to explore the role of PJP prophylaxis amongst glioma patients undergoing TMZ-RT. 23% (31/133) of physicians and 60% (44/73) of patients completed a survey. The median patient age was 42 (range 20-77); 85% (34/40) had completed adjuvant TMZ. Although only 2.4% (1/41) of patients received PJP prophylaxis, only one person (without PJP prophylaxis) was hospitalized for pneumonia. When presented with hypothetical PJP risks, 13.2% (5/38) of patients were concerned about PJP infection, while 26% (10/38) were concerned about potential side effects from prophylactic antibiotics. Most physicians (77%, 17/22) perceived the evidence for PJP prophylaxis as weak; 58% (11/19) did not routinely prescribe prophylaxis, and 73% (16/22) felt that PJP prophylaxis should be limited to patients with additional risk factors. Over 95% of physicians estimated that the incidence of PJP was < 1% in their last 5 years of practice regardless of PJP prophylaxis. For 73% (16/22) of physicians, to prescribe PJP prophylaxis, the risk of PJP infection needed to be 3-8%. The current recommendation to routinely prescribe PJP prophylaxis in patients receiving TMZ-RT in the absence of other risk factors warrants reconsideration.

Trends in Public Drug Plan Expenditures for Patients With Crohn Disease and Ulcerative Colitis Initiating Targeted Immune Modulator Therapy

The objective of this analysis was to examine the changes in drug expenditures with the initiation of targeted immune modulator (TIM) treatment in patients diagnosed with Crohn disease (CD) and ulcerative colitis (UC). Patient cohorts for CD and UC were identified from hospitalizations in Canada. Expenditure data for TIMs with a Health Canada–approved indication for the treatment of CD or UC were extracted from all provincial drug plans (except Quebec) and Yukon from 2016 to 2021, and a descriptive analysis was performed to assess the expenditure patterns. Annual expenditures on TIMs for patients with CD increased each year from 2016 to 2019 before decreasing in 2020 and 2021, whereas expenditures on TIMs in UC increased each year, generally by a greater percentage than was observed in CD (peak percentage growth of 92.5% for UC versus 15.9% for CD in 2018). Expenditures associated with TIM initiation among patients with CD and UC were driven by infliximab and adalimumab, with the 2 drugs accounting for nearly all expenditures in both indications in 2016 and most expenditures in 2021. In both CD and UC, vedolizumab expenditures increased over time, as did the proportions of TIM expenditures on ustekinumab in CD and tofacitinib in UC, albeit to a lesser extent than vedolizumab.

Risk of Mortality Associated with Potentially Inappropriate Medication Use Including Opioids in Older Adults.

As the population ages, understanding the potential risks associated with inappropriate medication use becomes increasingly important. Given the lack of studies in this area, our objective was to study the risk of mortality associated with potentially inappropriate medication use involving opioids in community-dwelling older adults. Data came from a longitudinal study on older adults aged ≥ 65 years recruited in primary care clinics between 2011 and 2013 with an average follow-up of 4.25 years. Older adults were excluded if they used an opioid or had a malignant tumor diagnosis in the year before the study survey. A nested case-control within a cohort of older adults with at least one opioid claim during follow-up was used to evaluate the risk of all-cause mortality. Four controls per case were matched on follow-up time using risk-set sampling, i.e., while still at risk of death when their matched case died. The risk of mortality was estimated using conditional logistic regression analyses. Exposure to potentially inappropriate medication use involving opioids, defined using the Beers 2019 criteria, was assessed from provincial drug claims data in the 0-90 days before death. In a cohort of 472 community-dwelling older adults with an incident episode of opioid use, there were 40 casesmatched to 160 controls. Exposure to inappropriate medication use involving opioids in the 90 days before death was associated with an increased risk of mortality (odds ratio 6.81, 95% confidence interval 1.69-27.47),after adjusting for potential confounders. Exposure to inappropriate medication use involving opioids in the 90 days before death is associated with an increased risk of mortality in older adults. These findings can be used to encourage safer pain management strategies in older adults.

SHORTAGE OF ESSENTIAL MEDICINES DURING THE COVID-19 PANDEMIC: CROSS SECTIONAL STUDY FROM COMMUNITY PHARMACIES

Background: The drug shortage is a very serious issue regarding the quality of Health System of any country. The problem is increased in the pandemic causing serious issues to the health system. Objectives: The objective of current study was to evaluate the factors responsible for the drug shortages in Pakistan and way forward to avoid these problems in the future. Methodology: A cross-sectional observational study was carried out in different cities of Pakistan. An online form was designed after thorough literature review. The study population included Staff pharmacists, Pharmacy managers and pharmacists self-owning pharmacies. Data was then collected, analyzed using SPSS-26. Results: The majority of pharmacists agreed that Global restrictions on trade activities added to drug shortage during COVID-19. The knowledge was relatively higher in pharmacists of Punjab as compared to pharmacists of other provinces. Majority of pharmacist (52%) from Punjab province of Pakistan strongly believed that Provincial drug regulatory department should play its role effectively during the emergency crisis to prevent drug shortages during the pandemic. Conclusion: In order to prevent the problem of drug shortages, efforts should be made to control the factors responsible for the drug shortages and local production should be enhanced along with proper control by regulatory authorities.

The Impact of reference pricing on prescribing patterns, costs, and health services utilization of proton pump inhibitors: A quasi-experimental study in British Columbia, Canada

IntroductionThe Reference Drug Program (RDP) was established to steer patients toward equally safe and cost-effective medication under British Columbia's public drug coverage. Each RDP class covers at least one reference drug, and non-reference drugs are reimbursed up to the cost of the reference drug. In 2016, the RDP updated to include proton pump inhibitors (PPIs). This study evaluated the impact on drug expenditures, prescription patterns, and health services utilization. MethodsWe identified a cohort of individuals covered by Fair Pharmacare who used PPIs, and a control group of H2 Blockers users. We used interrupted time series analysis on administrative data from June 2014 to December 2019 on the following outcomes: new users, day supply, expenditures, drug costs, reference drug use, and physician visits and costs. ResultsThe RDP had little impact on overall PPI use patterns. We did not observe any changes in reference drug uptake, new users, physician visits, cost-savings, or significant changes to days supplied post-policy. Cost expenditure results were likely biased due to co-occurring changes to drug prices. ConclusionInclusion of PPIs to the RDP saw no cost-savings for the provincial drug program and had little impact on prescribing patterns. Overall, our findings are consistent with existing evidence that the RDP is safe for similar therapeutic alternatives, but the impact on PPI costs remains unclear.

Optune (NovoTTF-200A)

What Is the Indication Under Review?&#x0D; &#x0D; The indication under review is for the treatment of adults with newly diagnosed glioblastoma multiforme (ndGBM) following maximal debulking surgery and completion of radiotherapy together with and after standard of care maintenance chemotherapy. Glioblastoma is the development of cancer among glial cells in the central nervous system and is the most common form of brain cancer in Canada.&#x0D; &#x0D; What Is Optune?&#x0D; &#x0D; Optune is a medical device that produces alternating electrical fields called tumour-treating fields to target the growth of cancerous cells in addition to chemotherapy. Current treatment for glioblastoma consists of a combination of surgery, radiotherapy, and chemotherapy.&#x0D; &#x0D; How Did CADTH Evaluate This Device?&#x0D; &#x0D; To examine the value of Optune for the treatment of ndGBM, CADTH:&#x0D; &#x0D; reviewed and critically appraised the clinical and economic evidence submitted by the sponsor&#x0D; reviewed the literature to identify and describe ethical considerations relevant to the use of Optune, as well as to assess the validity of the sponsor’s modelling approaches, assumptions, and estimates regarding Optune&#x0D; sought input from patient and clinician groups and consulted an expert panel.&#x0D; &#x0D; &#x0D; &#x0D; What Did CADTH Find?&#x0D; Clinical Evidence&#x0D; &#x0D; This review included the EF-14 trial, a pivotal, multicentre, open-label randomized controlled trial that assessed the efficacy and safety of Optune plus temozolomide in adults with ndGBM following maximal debulking surgery and completion of radiotherapy, together with and after standard of care maintenance chemotherapy.&#x0D; Based on the single trial, there is evidence of low to moderate certainty that Optune plus temozolomide likely increases progression-free survival at 6 months of treatment and overall survival at 24 months of treatment compared to temozolomide alone. The treatment effect of Optune plus temozolomide on progression-free survival and overall survival may be dose-dependent, with at least 18 hours of daily use required for the most benefit.&#x0D; Overall, the evidence was of very low to moderate certainty due to concerns regarding selection bias and low generalizability of the results to real-world settings.&#x0D; &#x0D; Economic Evidence&#x0D; &#x0D; The submitted fee for Optune is $27,000 per month, which is added to the cost of temozolomide based on its public list price.&#x0D; The incremental cost-effectiveness ratio for Optune plus temozolomide versus temozolomide alone was $899,470 per quality-adjusted life-year (QALY) gained (incremental costs = $336,902; incremental QALYs = 0.37).&#x0D; Optune plus temozolomide was not considered cost-effective relative to temozolomide alone at conventional willingness-to pay thresholds (i.e., $50,000 per QALY gained and $100,000 per QALY gained). Consequently, a price reduction of between 91% and 97% would be required for Optune plus temozolomide to be considered cost-effective at a willingness-to-pay threshold between $50,000 and $100,000 per QALY gained.&#x0D; The budget impact of reimbursing Optune through the federal, provincial, and territorial public drug plans (excluding Quebec) is estimated to be $75,795,323 to cover 232 patients over the initial 3 years of funding.&#x0D; &#x0D; Ethical Considerations&#x0D; &#x0D; The extent to which Optune meets patients’ needs for an effective, accessible, and easily usable treatment may depend on an individual patient’s values and caregiver support network, especially as Optune requires managing an additional treatment modality and may require additional caregiver support.&#x0D; Further study on how — or if — factors such as functional status, race, sex, age, socioeconomic status, and availability of caregiver support have implications for device uptake and ability to adhere to treatment would be helpful to inform patient-centred and equitable use, given the diverse patient population in Canada.&#x0D; Careful attention must be paid to the quality of clinical consent conversations, including considerations of disease progression potentially impairing capacity to consent and requiring a substitute decision-maker.&#x0D; Equity-enhancing strategies for implementation will need to be explored to ensure that Optune is accessible in an equitable and effective manner for all eligible patients in Canada.&#x0D;

ADHD medications use and risk of mortality and unintentional injuries: a population-based cohort study

We assessed the association between the use of medications for attention-deficit/hyperactivity disorder (ADHD) and the risk of all-cause mortality and unintentional injuries leading to emergency department (ED) or hospital admission in individuals aged ≤24 years with ADHD. We conducted a population-based retrospective cohort study between 2000 and 2021 using Quebec health administrative data. Individuals were followed from the first ADHD diagnosis or ADHD medication claim until turning 25, death, or study end. Exposure was defined as mutually exclusive episodes of ADHD medication use and/or coverage under the public provincial drug plan (PDP): 1) covered and not treated with ADHD medication; 2) covered and treated with ADHD medication; and 3) not covered under the PDP. The risk of all-cause mortality and unintentional injuries associated with exposure episodes was estimated using multivariable survival analyses. The cohort included n = 217 192 individuals aged 1–24 years with a male to female ratio of close to 2:1. Compared to non-medication use, episodes of ADHD medication use, overall, were associated with reduced all-cause mortality (adjusted hazard ratio, aHR 0.61, 95% CI 0.48–0.76) and unintentional injury leading to ED (0.75, 0.74–0.77) or hospitalisation (0.71, 0.68–0.75). Episodes of stimulants were associated with a lower risk of all-cause mortality and reduced risk of unintentional injuries, while episodes with non-stimulants and with both stimulants and non-stimulants concomitantly were associated with reduced risk of unintentional injuries, but not of all-cause mortality. Although residual confounding cannot be excluded, stimulants may have a protective effect in terms of risk of all-cause mortality and both stimulants and non-stimulants for ADHD may reduce the risk of unintentional injuries. The findings of the current study should inform clinical decision making on the choice of starting a pharmacological treatment for ADHD, when a balance needs to be struck between expected benefits and possible risks.

Hepatitis C Prevalence, HCV awareness and Certain Psychological Factors in Patients with Opioid Use Disorder.

The objective of this study is to determine the prevalance of Hepatitis C Virus (HCV) in patients with Opioid Use Disorder and to investigate both the sociodemographic and psychological differences between patients with or without Hepatitis C Virus. Blood samples were taken from patients diagnosed with Opioid Use Disorder (OUD) who applied to Mersin Provincial Health Directorate Toros State Hospital Alcohol and Drug Addiction Treatment Center (AMATEM) between 01.09.2019-01.09.2020 and hepatitis virus markers, complete blood count and basic biochemistry were assessed. Sociodemographic Evaluation Form, Barratt Impulsivity Scale, Childhood Traumas Scale, Drug Use Disorders Identification Test (DUDIT), Temps-A Temperament Scale, Difficulty in Emotion Regulation Scale were applied to 107 patients with HCV and 101 patients without HCV who were selected by systematic sampling and the findings obtained were compared. Of the 1190 patients diagnosed with Opioid Use Disorder, 340 (28.5%) were found to be HCV positive. 107 HCV-positive and 101 HCVnegative patients who were selected for comparison were similar in terms of sociodemographic characteristics. Among HCV positive patients, the rate of intravenous drug use and needle sharing were significantly higher (p<0.001, p<0.001). Overall duration of substance use and intravenous substance use were significantly higher in HCV positive patients (p=0.024 and p=0.017). Similarly, HCV positive group were significantly more likely (p<0.001) to have heard of HCV before and significantly more likely (p=0.009) to know that HCV causes cirrhosis and liver cancer. Regarding the scores of Barratt Impulsivity Scale, Childhood Traumas Scale, Substance Use Disorder Recognition Test, DUDIT, Temps -A Temperament Scales applied to HCV positive and HCV negative patients with Opioid Use Disorder, no difference was found. The scores of the 'Non-Acceptance' factor of the Difficulties in Emotion Regulation Scale were found to be significantly higher in HCV positive patients with Opioid Use Disorder (p=0.020). Patients diagnosed with Opioid Use Disorder (OUD) have higher rates of HCV positivity compared to general public. Intravenous drug use significantly increases this risk. Half of HCV-positive patients were unaware that they have the virus and only a very small proportion received treatment. Therefore, examining each patient with OUD for HCV, treating positive patients in an effective referral system seems to be the an important step in the eradication of this disease in this population.

Drug-Resistant Characteristics, Genetic Diversity, and Transmission Dynamics of Multidrug-Resistant Mycobacterium tuberculosis in Jiangxi, China.

In this study, we aimed to determine the transmission pattern of multidrug-resistant tuberculosis (MDR-TB) isolates circulating in Jiangxi Province with whole-genome sequencing (WGS). In addition, we also sought to describe mutational resistome of MDR-TB isolates. A total of 115 MDR-TB isolates determined by the phenotypic proportion method of drug susceptibility testing between January 2018 and December 2022 from provincial drug surveillance (DRS) in Jiangxi were included in our analysis. The demographic data and treatment history were extracted from the National TB Registry System. WGS was used to analyze the genotypic characteristics of drug resistance and transmissions. About 62.6% of MDR-TB strains were isolated from cases that received previous anti-tuberculosis treatment. According to the WGS results, 96.5% were genotypic MDR-TB, and more than half of MDR-TB isolates tested were also resistant to streptomycin (59.1%), ethambutol (56.5%), and fluroquinolones (53.0%), while resistance to cycloserine and linezolid was lowest, only in two (1.7%) and one (0.9%) isolate, respectively. Ser450Leu in rpoB (57.9%), Ser315Thr in katG (74.1%), Met306Val in embB (40.0%), Lys43Arg in rpsL (75.0%), Ala90Val in gyrA (32.8%) were predominant mutant types among the rifampin-, isoniazid-, ethambutol-, streptomycin-, fluoroquinolones-resistant isolates, respectively. Lineage 2 (East Asian genotype) occurred at the highest frequency with 97 cases (84.3%), followed by lineage 4 (Euro-American genotype) with 18 cases (15.7%). Additionally, 5 clusters consisting of 10 isolates were identified in the present study, demonstrating a clustering rate of 8.7%. MDR/Rifampicin-Resistant (RR)-TB epidemic in this region is driven by lineage 2 clade that also show higher resistance to other anti-tuberculosis drugs. Lower cluster rates compared with a relatively higher proportion of new MDR-TB cases indicate that a considerable number of MDR-TB cases remain undiagnosed.

Psychotropic medication use pre and post-diagnosis of cluster B personality disorder: a Quebec’s health services register cohort

BackgroundCluster B personality disorders (PDs) are considered some of the most severe mental health conditions. Scarce evidence exists about the real-world utilization of psychotropics for cluster B PD individuals.ObjectiveWe aimed to uncover trends and patterns of psychotropic medication use among individuals diagnosed with cluster B PD in the year before and after their diagnosis and to identify factors associated with medication use in a large cohort of individuals newly diagnosed with cluster B PDs.MethodsWe conducted a population-based observational study using Quebec’s health services register. We identified Quebec residents aged ≥14 years and insured with the provincial drug plan with a first diagnosis of cluster B PD recorded between April 1, 2002, and March 31, 2019. Cluster B PD was defined with ICD-9/10 diagnostic codes. We retrieved all claims for the main psychotropic medication classes: antipsychotics, antidepressants, anxiolytics, mood stabilizers, and attention-deficit/hyperactivity disorder (ADHD) medications. We calculated the proportion of individuals exposed to these medication classes and analyzed trends over the years using robust Poisson regression models, adjusting for potential confounders. We used robust Poisson regression to identify factors associated with medication class use.ResultsWe identified 87,778 new cases of cluster B PD, with a mean age of 44.5 years; 57.5% were women. Most frequent psychiatric comorbidities in the five years before cluster B PD diagnosis were depression (50.9%), anxiety (49.7%), and psychotic disorders (37.5%). Most individuals (71.0%) received at least one psychotropic during the year before cluster B PD diagnosis, and 78.5% received at least one of these medications in the subsequent year. The proportion of users increased after the diagnosis for antidepressants (51.6–54.7%), antipsychotics (35.9–45.2%), mood stabilizers (14.8–17.0%), and ADHD medications (5.1–5.9%), and remained relatively stable for anxiolytics (41.4–41.7%). Trends over time showed statistically significant increased use of antipsychotics and ADHD medications, decreased use of anxiolytics and mood stabilizers, and a stable use of antidepressants.ConclusionPsychotropic medication use is highly prevalent among cluster B PD individuals. We observed an increase in medication use in the months following the diagnosis, particularly for antipsychotics, antidepressants, and mood stabilizers.

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

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

EVALUATING PNEUMOCYSTIS JIROVECII PNEUMONIA (PCP) PROPHYLAXIS IN PATIENTS WITH GLIOMA RECEIVING CONCURRENT TEMOZOLOMIDE AND RADIATION – A PATIENT AND PHYSICIAN SURVEY

Abstract Temozolomide (TMZ) given concurrently with radiation (TMZ-RT) is essential in glioma therapy. Pneumocystis jirovecii pneumonia (PCP) prophylaxis is required by provincial and national drug monographs based on two incidents of PCP in a pilot study. There is otherwise limited evidence to inform the need for PCP prophylaxis in this population. METHODS: We conducted a single-centre survey of patients and national survey of physicians on the role of PCP prophylaxis in patients with glioma receiving concurrent TMZ-RT. RESULTS: Fifteen percent (31/212) of physicians and 60% (44/73) of patients completed a survey. The median age of patients was 42 (20-77); 85% (34/40) had completed adjuvant TMZ, and 59% (24/41) were not offered PCP prophylaxis. After reviewing the hypothetical risks of PCP, 13.2% (5/38) of patients were concerned about PCP infection, whereas 26% (10/38) were concerned about potential side effects from prophylactic antibiotics. Physician participants included medical (29%, 9/31) radiation (29%, 9/31), and neuro-oncologists (32%, 10/31). Most physicians (77%, 17/22) felt the evidence informing PCP prophylaxis in this population was weak; 58% (11/19) were not routinely prescribing prophylaxis, and 73% (16/22) felt that PCP prophylaxis should be limited to patients with additional risk factors. Sixty-three percent (22/35) of patients and 57% (12/21) of physicians were interested in a clinical trial to assess the risk of PCP infection in this setting. CONCLUSION: Clinical equipoise exists on the role of PCP prophylaxis during and after TMZ-RT amongst patients and physicians. Rigorous prospective studies need to be conducted to inform and standardize best practices.

Practice and Thinking on the Construction of Provincial Professional Drug Inspector Team—Taking the Construction of Shandong Drug Inspector Team as an Example

Practice and Thinking on the Construction of Provincial Professional Drug Inspector Team—Taking the Construction of Shandong Drug Inspector Team as an Example

EE426 A Comparison of the Cost-Saving Impact of Biosimilar Switching Policies across Canadian Provinces: A Case-Study for a Ranibizumab Biosimilar

This examined the impact of differing ophthalmology biosimilar switching policies on cost-savings for Canadian payors. The anticipated budget impact of a ranibizumab biosimilar was estimated across ten provincial drug plans. Resulting analysis identified possible opportunities for increased drug plan cost-savings associated with adopting proactive biosimilar switching policies.

Drug shortages in China: a cross-sectional study

BackgroundDrug shortages significantly threaten public health and medical service provision worldwide. Research evidence on the complete picture of drug shortages is currently scant in China. This study aimed to provide a descriptive overview and a reference for alleviating of drug shortages in China.MethodsNational and provincial lists of drug shortages issued in China from 2018 to 2021 were collected and summarized. The information on essential medicines, medical insurance drugs, emergency drugs, and volume-based purchasing drugs was then matched with a drug shortage list to analyse the characteristics, proportion and incidence of drug shortage on each list based on the analysis of information such as dosage form, shortage frequency, and Anatomical Therapeutic Chemical (ATC) classification of the drugs in shortage.ResultsA total of 24 provinces issued drug shortages lists involving 408 drugs from 2018 to 2021. All 58 drugs in the national drug list were included on the provincial drug shortage list. Among all the drugs in shortage, the most significant shortage involved injections, accounting for 45.3% (185/408). Ninety-five drugs (23.3%) were in shortage 5 times (annual shortage > 1 time) or more in the provincial lists, and 199 drugs (48.8%) were on the shortage list only once. In terms of therapeutic property, nearly all categories of drugs had been reported in shortage, among which cardiovascular drugs, nervous system drugs, anti-tumor and immunomodulatory drugs, and blood and hematopoietic organ drugs accounted for more than 10%. There is no significant difference in drug shortage among economic regions. Comparing drugs in shortage and various lists, 81.9% (334/408), 51.0% (208/408) and 67.9% (277/408) fell on the National Medical Insurance Drug List, National Essential Medicines List, and WHO Model List of Essential Medicines, respectively, while the volume-based purchasing drugs accounted for 3.4% (14 drugs). The incidence of drug shortages on NEML, WHO Model List of Essential Medicines and medical insurance category A was significantly higher than that of medical insurance category B and volume-based purchasing drugs (P < 0.05). Of the Emergency Drugs List, 72.0% (36/50) also experienced shortages, significantly higher than all the above categories (P < 0.05).ConclusionsIn China, drug shortages were severe and complicated. Drug shortages vary among economic regions but are not significant. In comparison, the national procurement pattern of volume-based drug purchasing may be conducive to alleviating the drug shortage problem. Collaboration of all partners was recommended to ensure the supply of clinically necessary drugs.

The Impact of Suboxone's Market Exclusivity on Cost of Opioid Use Disorder Treatment.

Buprenorphine-naloxone is an essential part of the response to opioid poisoning rates in North America. Manipulating market exclusivity is a strategy manufacturers use to increase profitability, as evidenced by Suboxone in the USA. To investigate excess costs of buprenorphine-naloxone due to unmerited market exclusivity (no legal patent or data protection) in Canada. Using controlled interrupted time-series, this study examined changes in the cost of buprenorphine-naloxone before and after the first generics were listed on public formularies. Methadone cost was the control. Public data from the Canadian Institute of Health Information in British Columbia, Manitoba, and Saskatchewan were used. All buprenorphine-naloxone and methadone claims (2010-2019) accepted for payment by the provincial drug plan/programme were collected. Primary outcome was mean cost per mg of buprenorphine-naloxone after the first listing of generics. Mean cost per mg of buprenorphine-naloxone before the first listing of generics was $1.21 CAD in British Columbia, $1.27 CAD in Manitoba, and $0.85 CAD in Saskatchewan. Following the introduction of generics, the cost per mg decreased by $0.22 CAD (95% CI - 0.33 to - 0.10; p = 0.0014) in British Columbia, $0.36 CAD (95% CI - 0.58 to - 0.13; p = 0.004) in Manitoba, and $0.27 CAD (95% CI - 0.50 to - 0.05; p = 0.03) in Saskatchewan. Mean cost per mg decreased by $0.26 CAD (95% CI - 0.38 to - 0.13; p = 0.0004) after a third generic was introduced in British Columbia. Excess costs to public formularies during the 4- to 5-year period prior to the listing of generics were $1,992,558 CAD in British Columbia, $80,876 CAD in Manitoba, and $4130 CAD in Saskatchewan. If buprenorphine-naloxone cost $0.61 CAD (mean cost after the third generic entered) instead of $1.21 CAD per mg during the pre-generics period, public payers in British Columbia could have saved $5,016,220 CAD between 2011 and 2015. Unmerited 6years of market exclusivity for brand-name buprenorphine-naloxone in Canada resulted in substantial excess costs. There is an urgent need to implement policies that can help reduce costs for high-priority drugs in Canada.

"It's just not the same": Exploring PWUD' perceptions of and experiences with drug policy and SCS services change in a Canadian City.

Shifting political contexts can significantly alter drug policy approaches and available supports for People Who Use Drugs (PWUD). The purpose of this study was to explore how shifts in provincial drug policy approaches, specifically the replacement of a Safe Consumption Site (SCS) with a smaller mobile Overdose Prevention Site (OPS) in Lethbridge, Alberta Canada, impacted PWUD' access to and experiences with harm reduction services. We conducted semi-structured interviews with 50 PWUD in the City of Lethbridge, Canada. Through traditional fieldwork, we recruited participants within, and just outside of, downtown Lethbridge. Using a standardized general prompt guide to begin interviews, participants were asked a variety of questions about their experiences with and perceptions of SCS access and changes to SCS provisions. Interviews were audio recorded, then transcribed, coded, and analyzed. Participants reported regular and frequent access and overall positive experiences with the SCS, despite also noting certain operational barriers (e.g., long wait times). By contrast, participants reported more limited use of the new OPS compared to the SCS because of three main reasons: (1) concerns about location; (2) smoking room elimination; and (3) lack of social space and activities. Overall, changes to SCS provision produced a range of negative consequences for PWUD in Lethbridge. These relate to perceived increases in drug-related harms (e.g., increased overdoses) as well as negative social impacts (e.g., lack of place to meet other people). Findings from this study provide preliminary indications of the importance of understanding how contextual and locally-specific elements (location, limits on permitted route administration, and social aspects) can work together to facilitate SCS uptake and even overcome traditional SCS barriers. Conversely, the absence of such elements can hinder SCS uptake. Results show that the value of SCS might differ across locations, pointing to the need for further locally-grounded examinations of harm reduction service uptake and experience.