Adapting the Opening Minds Stigma Scale for Healthcare Providers to Measure Opioid-Related Stigma.

The opioid crisis in Canada continues to cause a devastating number of deaths. Community-based naloxone programs have been identified as one of the solutions for combatting this crisis; however, there are disparities in which pharmacies stock and offer naloxone. Opioid-related stigma is a major barrier for limited naloxone distribution through pharmacies. Therefore, the development of anti-stigma interventions is crucial to improve naloxone distribution in Canada. However, there is no validated tool to specifically measure opioid-related stigma. The Opening Minds Stigma Scale for Healthcare Providers (OMS-HC) is a validated scale used to measure mental illness-related stigma. This study will adapt the OMS-HC by using four different opioid-related terminologies to determine which is the most stigmatizing to use in an opioid-related anti-stigma intervention. Pharmacy students completed four versions of the adapted OMS-HC. The average OMS-HC scores and Cronbach's α co-efficient were calculated for each version. The term "opioid addiction" was found to be the most stigmatizing term among participants and will be used in the adapted version of the OMS-HC in a future anti-stigma interventions.

Benzofuran and Benzo[b]thiophene-2-carboxamide Derivatives as Modulators of Amyloid Beta (Aß42) Aggregation.

A group of N-phenylbenzofuran-2-carboxamide and N-phenylbenzo[b]thiophene-2-carboxamide derivatives were designed and synthesized as a novel class of Aß42 aggregation modulators. In the thioflavin-T based fluorescence aggregation kinetics study, compounds 4a, 4b, 5a and 5b possessing a methoxyphenol pharmacophore were able to demonstrate concentration dependent inhibition of Aß42 aggregation with maximum inhibition of 54% observed for compound 4b. In contrast, incorporation of a 4-methoxyphenyl ring in compounds 4d and 5d led to a significant increase in Aß42 fibrillogenesis demonstrating their ability to accelerate Aß42 aggregation. Compound 4d exhibited 2.7-fold increase in Aß42 fibrillogenesis when tested at the maximum concentration of 25 µM. These results were further confirmed by electron microscopy studies which demonstrates the ability of compounds 4a, 4b, 4d, 5a, 5b and 5d to modulate Aß42 fibrillogenesis. Compounds 5a and 5b provided significant neuroprotection to mouse hippocampal neuronal HT22 cells against Aß42-induced cytotoxicity. Molecular docking studies suggest that the orientation of the bicyclic aromatic rings (either benzofuran or benzo[b]thiophene) plays a major role in moderating their ability to either inhibit or accelerate Aß42 aggregation. Our findings support the application of these novel derivatives as pharmacological tools to study the mechanisms of Aß42 aggregation.

Association Between Opioid-Related Mortality and History of Surgical Procedure: A Population-Based Case-Control Study.

Objective: This study examined whether there is an association between opioid-related mortality and surgical procedures. Methods: A case-control study design using deceased controls compared individuals with and without opioid death and their exposure to common surgeries in the preceding 4 years. This population-based study used linked death and hospitalization databases in Canada (excluding Quebec) from January 01, 2008 to December 31, 2017. Cases of opioid death were identified and matched to 5 controls who died of other causes by age (±4 years), sex, province of death, and date of death (±1 year). Patients with HIV infection and alcohol-related deaths were excluded from the control group. Logistic regression was used to determine if there was an association between having surgery and death from an opioid-related cause by estimating the crude and adjusted odds ratios (ORs) with the corresponding 95% confidence interval (CI). Covariates included sociodemographic characteristics, comorbidities, and the number of days of hospitalization in the previous 4 years. Results: We identified 11,865 cases and matched them with 59,345 controls. About 11.2% of cases and 12.5% of controls had surgery in the 4 years before their death, corresponding to a crude OR of 0.89 (95% CI: 0.83-0.94). After adjustment, opioid mortality was associated with surgical procedure with OR of 1.26 (95% CI: 1.17-1.36). Conclusions: After adjusting for comorbidities, patients with opioid mortality were more likely to undergo surgical intervention within 4 years before their death. Clinicians should enhance screening for opioid use and risk factors when considering postoperative opioid prescribing.

Estimating implicit and explicit racial and ethnic bias among community pharmacists in Canada.

Background: Bias, whether implicit (unconscious) or explicit (conscious), can lead to preferential treatment of specific social groups and antipathy towards others. When healthcare professionals (HCPs), including pharmacists, act on these biases, patient care and health outcomes can be adversely affected. This study aims to estimate implicit and explicit racial/ethnic bias towards Black and Arab people among community pharmacists in Ontario, Canada. Methods: Community pharmacists participated in a secure, web-based survey using a cross-sectional design that included Harvard's Race and Arab Implicit Association Tests (IATs) to examine bias towards Black and Arab people. Explicit (stated) preferences were measured by self-report. Data were analyzed using descriptive and inferential statistics. Results: The study surveyed 407 community pharmacists, 56.1 % of whom were women with an average age of 46.9. Implicit Association Test (IAT) results showed a statistically significant moderate preference for white people over both Black (mean IAT = 0.41) and Arab people (mean IAT = 0.35). However, most pharmacists explicitly stated that they had no racial/ethnic preference, with 75.7 % expressing a neutral preference between Black and white and 66.6 % neutral between Arab and white. However, a slight preference for white individuals was observed. Demographic factors such as age, place of birth, race/ethnicity, and experience significantly impacted IAT scores. For example, older, Canadian-born, white pharmacists with more experience displayed higher implicit bias scores. A mild correlation was found between implicit and explicit bias, indicating as implicit bias increases, explicit bias tends to become more negative. Conclusions: This study is the first to explore the issue of pharmacist bias in Canada and concentrate on anti-Arab bias. Our findings reveal that Ontario community pharmacists tend to have an unconscious inclination towards white people, which calls for further understanding of this matter. Additionally, we discovered a moderate degree of anti-Arab bias, indicating that studies on other HCPs should consider bias against this social group. Educational interventions are needed to address the implicit biases among community pharmacists in Ontario, Canada. These findings should aim to raise self-awareness of biases, educate about the potential implications of these biases on patient care, and provide strategies to reduce bias.

An economic evaluation of community pharmacy-dispensed naloxone in Canada.

Aims: To determine the cost-effectiveness of pharmacy-based intranasal (IN) and intramuscular (IM) naloxone distribution in Canada. Methods: We developed a state-transition model for pharmacy-based naloxone distribution, every 3 years, to illicit, prescription, opioid-agonist therapy and nonopioid use populations compared to no naloxone distribution. We used a monthly cycle length, lifetime horizon and a Canadian provincial Ministry of Health perspective. Transition probabilities, cost and utility data were retrieved from the literature. Costs (2020) and quality-adjusted life years (QALY) were discounted 1.5% annually. Microsimulation, 1-way and probabilistic sensitivity analyses were conducted. Results: Distribution of naloxone to all Canadians compared to no distribution prevented 151 additional overdose deaths per 10,000 persons, with an incremental cost-effectiveness ratio (ICER) of $50,984 per QALY for IM naloxone and an ICER of $126,060 per QALY for IN naloxone. Distribution of any naloxone to only illicit opioid users was the most cost-effective. One-way sensitivity analysis showed that survival rates for illicit opioid users were most influenced by the availability of either emergency medical services or naloxone. Conclusion: Distribution of IM and IN naloxone to all Canadians every 3 years is likely cost-effective at a willingness-to-pay threshold of $140,000 Canadian dollars/QALY (~3 × gross domestic product from the World Health Organization). Distribution to people who use illicit opioids was most cost-effective and prevented the most deaths. This is important, as more overdose deaths could be prevented through nationwide public funding of IN naloxone kits through pharmacies, since individuals report a preference for IN naloxone and these formulations are easier to use, save lives and are cost-effective. Can Pharm J (Ott) 2024;157:xx-xx.

The Interplay Between Cholesterol and Amyloid-ß on HT22 Cell Viability, Morphology, and Receptor Tyrosine Kinase Signaling.

BACKGROUND: There is a lack of understanding in the molecular and cellular mechanisms of Alzheimer's disease that has hindered progress on therapeutic development. The focus has been on targeting toxic amyloid-ß (Aß) pathology, but these therapeutics have generally failed in clinical trials. Aß is an aggregation-prone protein that has been shown to disrupt cell membrane structure in molecular biophysics studies and interfere with membrane receptor signaling in cell and animal studies. Whether the lipid membrane or specific receptors are the primary target of attack has not been determined. OBJECTIVE: This work elucidates some of the interplay between membrane cholesterol and Aß42 on HT22 neuronal cell viability, morphology, and platelet-derived growth factor (PDGF) signaling pathways. METHODS: The effects of cholesterol depletion by methyl-ß-cyclodextrin followed by treatment with Aß and/or PDGF-AA were assessed by MTT cell viability assays, western blot, optical and AFM microscopy. RESULTS: Cell viability studies show that cholesterol depletion was mildly protective against Aß toxicity. Together cholesterol reduction and Aß42 treatment compounded the disruption of the PDGFα receptor activation. Phase contrast optical microscopy and live cell atomic force microscopy imaging revealed that cytotoxic levels of Aß42 caused morphological changes including cell membrane damage, cytoskeletal disruption, and impaired cell adhesion; cell damage was ameliorated by cellular cholesterol depletion. CONCLUSIONS: Cholesterol depletion impacted the effects of Aß42 on HT22 cell viability, morphology, and receptor tyrosine kinase signaling.

Lithium isotopes differentially modify mitochondrial amorphous calcium phosphate cluster size distribution and calcium capacity.

Lithium is commonly prescribed as a mood stabilizer in a variety of mental health conditions, yet its molecular mode of action is incompletely understood. Many cellular events associated with lithium appear tied to mitochondrial function. Further, recent evidence suggests that lithium bioactivities are isotope specific. Here we focus on lithium effects related to mitochondrial calcium handling. Lithium protected against calcium-induced permeability transition and decreased the calcium capacity of liver mitochondria at a clinically relevant concentration. In contrast, brain mitochondrial calcium capacity was increased by lithium. Surprisingly, 7Li acted more potently than 6Li on calcium capacity, yet 6Li was more effective at delaying permeability transition. The size distribution of amorphous calcium phosphate colloids formed in vitro was differentially affected by lithium isotopes, providing a mechanistic basis for the observed isotope specific effects on mitochondrial calcium handling. This work highlights a need to better understand how mitochondrial calcium stores are structurally regulated and provides key considerations for future formulations of lithium-based therapeutics.

Search for lithium isotope effects in neuronal HT22 cells.

Lithium has been used as a treatment for bipolar disorder for over half a century, but there has thus far been no clinical differentiation made between the two naturally occurring stable isotopes (6Li and 7Li). While the natural lithium salts commonly used in treatments are composed of a mixture of these two stable isotopes (approximately 7.59% 6Li and 92.41% 7Li), some preliminary research indicates the above two stable isotopes of lithium may have differential effects on rat behaviour and neurophysiology. Here, we evaluate whether lithium isotopes may have distinct effects on HT22 neuronal cell viability, GSK-3-ß phosphorylation in HT22 cells, and GSK-3-ß kinase activity. We report no significant difference in lithium isotope toxicity on HT22 cells, nor in GSK-3-ß phosphorylation, nor in GSK-3-ß kinase activity between the two isotopes of lithium.

Differential Effects of Endocannabinoids on Amyloid-Beta Aggregation and Toxicity.

The regulation and metabolism of the endocannabinoid system has received extensive attention for their potential neuroprotective effect in neurodegenerative diseases such as Alzheimer's disease (AD), which is characterized by amyloid ß (Aß) -induced cell toxicity, inflammation, and oxidative stress. Using in vitro techniques and two cell lines, the mouse hippocampus-derived HT22 cells and Chinese hamster ovary (CHO) cells expressing human cannabinoid receptor type 1 (CB1), we investigated the ability of endocannabinoids to inhibit Aß aggregation and protect cells against Aß toxicity. The present study provides evidence that endocannabinoids N-arachidonoyl ethanol amide (AEA), noladin and O-arachidonoyl ethanolamine (OAE) inhibit Aß42 aggregation. They were able to provide protection against Aß42 induced cytotoxicity via receptor-mediated and non-receptor-mediated mechanisms in CB1-CHO and HT22 cells, respectively. The aggregation kinetic experiments demonstrate the anti-Aß aggregation activity of some endocannabinoids (AEA, noladin). These data demonstrate the potential role and application of endocannabinoids in AD pathology and treatment.

Drug-Drug Interaction of the Sodium Glucose Co-Transporter 2 Inhibitors with Statins and Myopathy: A Disproportionality Analysis Using Adverse Events Reporting Data.

INTRODUCTION: An increased risk of myopathy due to a potential interaction between sodium glucose co-transporter-2 inhibitors (SGLT-2i) and HMG-CoA reductase inhibitors (statins) has been suggested by case reports. OBJECTIVE: We aimed to assess if the reporting of myopathy is disproportionally higher among people using both SGLT-2i and statins compared to using either SGLT-2i or statins alone. METHODS: We conducted a disproportionality analysis using data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). We included reports with at least one antihyperglycemic agent. We compared the proportion of myopathy cases to non-cases between those not using SGLT-2i or statins, using SGLT-2i only, statins only, or both. We calculated the reporting odds ratio and 95% confidence interval. We further stratified by individual SGLT-2i and selected statins (rosuvastatin or atorvastatin). RESULTS: We included 688,388 reports with at least one antihyperglycemic agent recorded, of which 9.80% had at least one SGLT-2i agent. Among all included reports, there were a total of 2202 myopathy cases with the majority, 61.26%, occurring among those using statins alone and only 2.72% of myopathy cases were among those using both SGLT-2i and statins together. Reporting of myopathy was not disproportionally higher among those reporting the use of SGLT-2i with statins (reporting odds ratio 2.95, 95% confidence interval 2.27-3.85) compared to statins alone (reporting odds ratio 6.41, 95% confidence interval 5.86-7.02). CONCLUSIONS: Reports of myopathy were not disproportionally higher among those using SGLT-2i with statins compared to SGLT-2i or statins alone at the class level. Further observational studies may be needed to better assess this interaction at the agent level.

Protocol for the Optimizing Naloxone Dispensing in Pharmacies (ONDP) Online Continuing Education Program: A Randomized Controlled Trial.

The number of opioid-related deaths in Canada has steadily increased since 2016 and the COVID-19 pandemic has worsened this trend. Naloxone has been pivotal for reducing opioid-related harms and death, and pharmacists play a crucial role in ensuring the supply of naloxone to Canadians through community pharmacies. However, naloxone dispensing by pharmacists is not optimal; in fact, in Ontario, only 50% of pharmacists offer naloxone, despite national guidelines that pharmacists should offer naloxone to everyone with an opioid prescription. When asked why pharmacists do not proactively offer naloxone, recent research has identified that pharmacists need continuing education to boost confidence and knowledge on how to start conversations with patients. The study involves a delayed start, double-blind randomized controlled trial, for Canadian licensed pharmacists and pharmacy technicians. The goals of the program are to increase Canadian pharmacy professional's knowledge, confidence, and motivation to proactively offer naloxone, as well as to decrease stigma associated with naloxone. The program incorporates behaviour change techniques from the Theoretical Domains Framework and the Theory of Planned Behaviour. The intervention program includes three modules that focus on improving pharmacists' communication skills by teaching them how to proactively offer naloxone, while the control group will complete a reading assignment on the naloxone consensus guidelines. The program will involve a process and outcome evaluation in addition to a contribution analysis. This program is important for breaking down previously identified barriers and knowledge gaps for why pharmacists currently do not proactively offer naloxone. This study will provide important new information about what behaviour change techniques are successful in improving confidence and motivation in the pharmacy profession and in an online environment. Findings from this study can be used to produce a national naloxone education program that can also be implemented into current pharmacy school curriculum.

Assessing the impact of a cannabis course on pharmacy students' understanding, beliefs and preparedness regarding medical and recreational cannabis.

BACKGROUND: With the legalization of cannabis in Canada in 2018, pharmacists are increasingly likely to encounter patients using this substance. The primary objective of this pre-post questionnaire study was to evaluate the impact of an accredited cannabis course on the understanding, beliefs, perceptions and knowledge of undergraduate PharmD students. METHODS: A 38-question, web-based survey generated in REDCap was administered to third-year PharmD students at the University of Waterloo, prior to and right after taking an accredited cannabis course. The pre- and postsurvey data were analyzed using SPSS version 25. Pearson chi-square tests were performed on questions in which answers consisted of qualitative categorical data. Two-sided t tests were performed to test the significance of mean differences of questions measuring continuous variables. RESULTS: In a class of 120 students, 110 completed the presurvey and 79 students completed the postsurvey. After the course, students were more likely to report being knowledgeable and prepared for patient encounters dealing with medical and recreational cannabis, understanding that medical cannabis should be prescribed for select (vs all) medical conditions, rating the quality of evidence as poor to moderate for medical use of cannabis, understanding that medical documents should be more prescriptive and understanding that cannabis should not be sold in pharmacies (p < 0.05). INTERPRETATION: With cannabis education a part of their curriculum, pharmacy students felt more prepared to engage patients using cannabis both medically and recreationally. Furthermore, students were more cautious regarding the potential use of cannabis therapeutically and indicated that more oversight should be in place. Can Pharm J (Ott) 2021;154:xx-xx.

The role of pharmacists in opioid stewardship: A scoping review.

BACKGROUND: The opioid epidemic is an international public health concern. Pharmacists are in a strategic position to promote and implement effective opioid stewardship due to both their central role on health care teams and frequent interaction with patients. Despite this integral role, pharmacists do not have harmonized scopes of practice in opioid stewardship. OBJECTIVES: This scoping review was conducted to identify and critically review the role of pharmacists in opioid stewardship and identify future areas of study. METHODS: The scoping review was conducted according to the methodological framework proposed by Arksey and O'Malley, which was further modified by the Joanna Briggs Institute. Six databases were searched for original, peer-reviewed research; PubMed (MEDLINE), Ovid Embase, Ovid International Pharmaceutical Abstracts, Scopus, Cochrane Library, and APA PsycInfo. RESULTS: In 92% of the included studies (n = 77), opioid stewardship interventions led by either a pharmacist or in an interdisciplinary team resulted in improvements in at least one outcome measure, with education and medication therapy adjustments being the most predominant activities. Other areas supported by evidence include community stakeholder education, policy and guideline setting, and risk assessment. CONCLUSION: This scoping review provides valuable insight into the various roles pharmacists can have in opioid stewardship. The findings from this review identified opioid stewardship activities that can make significant contributions towards reducing the impact of the opioid crisis. This review informs future research and has the potential to influence pharmacy practice on a national and international scale.

Investigating Community Pharmacy Take Home Naloxone Dispensing during COVID-19: The Impact of One Public Health Crisis on Another.

A recent report found that the number of opioid-related deaths in Ontario in the first 15 weeks of the COVID-19 pandemic was 38.2% higher than in the 15 weeks before the pandemic. Our study sought to determine if pharmacy professionals self-reported an increase or decrease in naloxone provision due to the pandemic and to identify adjustments made by pharmacy professionals to dispense naloxone during the pandemic. A total of 231 Ontario community pharmacy professionals completed an online survey. Pharmacy professionals' barriers, facilitators, and comfort level with dispensing naloxone before and during the pandemic were identified. The sample consisted of mostly pharmacists (99.1%). Over half (51.1%) reported no change in naloxone dispensing, while 22.9% of respondents reported an increase and 24.7% a decrease. The most common adjustments made during the pandemic were training patients how to administer naloxone over video or phone, delivering naloxone kits, and pharmacy technicians offering naloxone at prescription intake. Over half (55%) of participants said the top barrier for dispensing was that patients did not request naloxone. Naloxone distribution through pharmacies could be further optimized to address the increased incidence of overdose deaths during the pandemic. Future research should investigate the reasons for changes in naloxone dispensing.

Chronic early-life social isolation affects NMDA and TrkB receptor expression in a sex-specific manner.

Exposing mammals to adverse social environments early in life can affect brain development in ways that alter adult behaviour. For example, chronic, early-life social isolation (CELSI) has been found to cause novelty-induced hyperactivity, impaired pre-pulse inhibition, and enhanced anxiety-related behaviour. Although the molecular mechanism(s) underlying the embedding of CELSI have not been fully elucidated, evidence suggests changes in the level of excitatory neurotransmission and neurotrophic factor signalling may be quite important. Since much of the work in this area has focused upon mRNA-level analyses, and has shown variable responses across both brain region and animal sex, our study aimed to explore the impact of CELSI on the expression of two important plasticity-related proteins (Tropomyosin receptor kinase B and the GluN2B subunit of the NMDA receptor) in the pre-frontal cortex and hippocampus of both male and female rats. We observed that the expression of both proteins was clearly changed by CELSI, but that the effect occurred in a sex (but not region) specific manner. Our results support the growing view that early-life adversity can cause structural changes reasonably associated with adult behaviour, and emphasise that the study of such changes benefits from a sex-based analysis.

The role of pharmacists in opioid stewardship: Protocol.

BACKGROUND: The opioid crisis is a worldwide public health concern. In North America, evidence suggests that the increase in opioid prescriptions correlates with the observed increase in opioid-related mortality and morbidity. Pharmacists are in a strategic position to promote effective opioid stewardship as they have a central role on healthcare teams. However, in many contexts, pharmacists do not have a harmonized scope of practice and no standardized opioid stewardship approach has been implemented. OBJECTIVES: A scoping review will be conducted to identify and summarize evidence on the role of pharmacists in opioid stewardship and identify areas for future study. METHODS: The scoping review will be conducted according to the methodological framework proposed by Arksey and O'Malley, which was further modified by the Joanna Briggs Institute. Six databases will be searched which include PubMed, Embase, International Pharmaceutical Abstracts, Scopus, Cochrane Library, and APA PsycInfo. PROJECT IMPACT: The findings of this review will identify opioid stewardship activities that can contribute towards reducing the impact of the opioid crisis. Additionally, it will provide foundational strategies to promote policy level change and foster a harmonized scope of practice. This review has the potential to inform future research, impact pharmacy practice, and drive policy change.