Coordination of oral anticoagulant care at hospital discharge (COACHeD): pilot randomised controlled trial.

OBJECTIVES: To evaluate whether a focused, expert medication management intervention is feasible and potentially effective in preventing anticoagulation-related adverse events for patients transitioning from hospital to home. DESIGN: Randomised, parallel design. SETTING: Medical wards at six hospital sites in southern Ontario, Canada. PARTICIPANTS: Adults 18 years of age or older being discharged to home on an oral anticoagulant (OAC) to be taken for at least 4 weeks. INTERVENTIONS: Clinical pharmacologist-led intervention, including a detailed discharge medication management plan, a circle of care handover and early postdischarge virtual check-up visits to 1 month with 3-month follow-up. The control group received the usual care. OUTCOMES MEASURES: Primary outcomes were study feasibility outcomes (recruitment, retention and cost per patient). Secondary outcomes included adverse anticoagulant safety events composite, quality of transitional care, quality of life, anticoagulant knowledge, satisfaction with care, problems with medications and health resource utilisation. RESULTS: Extensive periods of restriction of recruitment plus difficulties accessing patients at the time of discharge negatively impacted feasibility, especially cost per patient recruited. Of 845 patients screened, 167 were eligible and 56 were randomised. The mean age (±SD) was 71.2±12.5 years, 42.9% females, with two lost to follow-up. Intervention patients were more likely to rate their ability to manage their OAC as improved (17/27 (63.0%) vs 7/22 (31.8%), OR 3.6 (95% CI 1.1 to 12.0)) and their continuity of care as improved (21/27 (77.8%) vs 2/22 (9.1%), OR 35.0 (95% CI 6.3 to 194.2)). Fewer intervention patients were taking one or more inappropriate medications (7 (22.5%) vs 15 (60%), OR 0.19 (95% CI 0.06 to 0.62)). CONCLUSION: This pilot randomised controlled trial suggests that a transitional care intervention at hospital discharge for older adults taking OACs was well received and potentially effective for some surrogate outcomes, but overly costly to proceed to a definitive large trial. TRIAL REGISTRATION NUMBER: NCT02777047.

Proarrhythmic major adverse cardiac events with donepezil: A systematic review with meta-analysis.

BACKGROUND: Cholinesterase inhibitors (ChEIs) are regularly used in Alzheimer's disease. Of the three ChEIs approved for dementia, donepezil is among the most prescribed drugs in the United States with nearly 6 million prescriptions in 2020; however, it is classified as a "known risk" QT interval-prolonging medication (QTPmed). Given this claim is derived from observational data including single case reports, we aimed to evaluate high-quality literature on the frequency and nature of proarrhythmic major adverse cardiac events (MACE) associated with donepezil. METHODS: We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onwards for randomized controlled trials (RCTs) involving patients age ≥18 years comparing donepezil to placebo. The MACE composite included mortality, sudden cardiac death, non-fatal cardiac arrest, Torsades de pointes, ventricular tachyarrhythmia, seizure or syncope. Random-effects meta-analyses were performed with a treatment-arm continuity correction for single and double zero event studies. RESULTS: Sixty RCTs (n = 12,463) were included. Twenty-five of 60 trials (n = 5886) investigated participants with Alzheimer's disease and 33 trials monitored electrocardiogram data. The mean follow-up duration was 31 weeks (SD = 36). Mortality was the most commonly reported MACE (252/331, 75.8% events), the remainder were syncope or seizures, with no arrhythmia events. There was no increased risk of MACE with exposure to donepezil compared to placebo (risk ratio [RR] 1.08, 95% CI 0.88-1.33, I2 = 0%) and this was consistent in the subgroup analysis of trials including participants with cardiovascular morbidities (RR 1.14, 95% CI 0.88-1.47). Subgroup analysis suggested a trend toward more events with donepezil with follow-up ≥52 weeks (RR: 1.32, 0.98-1.79). CONCLUSIONS: This systematic review with meta-analysis found donepezil may not be arrhythmogenic. Donepezil was not associated with mortality, ventricular arrhythmias, seizure or syncope, although longer durations of therapy need more study. Further research to clarify actual clinical outcomes related to QTPmed is important to inform prescribing practices.

Characteristics of Drug Poisonings Seen in the Emergency Department of an Urban Hospital.

Background: Drug poisoning, either intentional or non-intentional, is a frequent diagnosis in the emergency department (ED), necessitating patient management from multiple services. Objective: To describe the drug poisonings seen in the ED of a large academic urban hospital. Methods: This retrospective descriptive study used 3 years of data (2018-2020) abstracted from the hospital's electronic medical record system and linked to validated, coded extracts from the Canadian Institute for Health Information Discharge Abstract Database. Patients with a diagnosis of acute drug poisoning who presented to the ED were identified on the basis of International Statistical Classification of Diseases and Related Health Problems, 10th revision, Canada (ICD-10-CA) codes, and data were collected for demographic characteristics, the drugs involved, in-hospital management, and inpatient outcomes. Patients with diagnosis of an acute drug reaction, inebriation, or nondrug or in-hospital poisoning were excluded. Data were stratified and analyzed in relation to the intent of drug poisoning. Results: A total of 2983 visits for drug poisoning, involving 2211 unique patients (mean age 38.3 [standard deviation 16.2] years, 54.7% female), were included, yielding an overall incidence rate of 15.7 drug poisonings per 1000 ED visits (8.1 intentional, 6.4 non-intentional, and 1.3 unknown intent). Among the 1505 intentional drug poisonings, the most prevalent drug sources were antidepressants (n = 405, 26.9%), benzodiazepines (n = 375, 24.9%), and acetaminophen (n = 329, 21.9%); in contrast, opioids (n = 594, 48.1%) were most prevalent for the 1236 non-intentional poisonings. For 716 (24.0%) of the poisoning visits, the patient was admitted to acute care services, and the in-hospital mortality rate was 1.0% (n = 31). In addition, 111 patients (9.0%) with non-intentional drug poisoning left against medical advice. Finally, for 772 (25.9%) of the poisoning visits, the patient returned to the ED after discharge with a subsequent drug poisoning. Conclusions: Drug poisonings are a common cause of visits to urban EDs. They are rarely fatal but are associated with substantial utilization of hospital resources and considerable recidivism.

Contexte: L'intoxication médicamenteuse, intentionnelle ou non, est un diagnostic fréquent dans le service des urgences (SU); elle nécessite la prise en charge des patients par plusieurs services. Objectif: Décrire les intoxications médicamenteuses observées dans le SU d'un grand hôpital universitaire urbain. Méthodologie: Pour cette étude rétrospective et descriptive, des données contenues dans le système de dossiers médicaux électroniques de l'hôpital et liées à des extraits validés et codés de la base de données sur les congés des patients de l'Institut canadien d'information sur la santé pendant 3 ans (2018­2020) ont été utilisées. Les patients ayant reçu un diagnostic d'intoxication médicamenteuse aiguë qui se sont présentés à l'urgence ont été identifiés sur la base des codes de la Classification statistique internationale des maladies et des problèmes de santé connexes, 10e version, Canada (CIM-10-CA), et des données ont été recueillies pour les caractéristiques démographiques, les médicaments impliqués, la prise en charge à l'hôpital et les résultats pour les patients hospitalisés. Les patients présentant un diagnostic de réaction médicamenteuse aiguë, d'ébriété ou d'intoxication non médicamenteuse ou à l'hôpital ont été exclus. Les données ont été stratifiées et analysées en fonction de l'intention de l'empoisonnement médicamenteux. Résultats: Au total, 2983 cas mettant en cause 2211 patients (âge moyen 38,3 [écart type 16,2] ans, dont 54,7 % de femmes) ont été inclus; les résultats ont donné un taux d'incidence global de 15,7 intoxications médicamenteuses pour 1000 visites au SU (8,1 intentionnelles; 6,4 non intentionnelles; et 1,3 intention inconnue). Parmi les 1505 intoxications médicamenteuses intentionnelles, les médicaments les plus répandues étaient les antidépresseurs (n = 405, 26,9 %), les benzodiazépines (n = 375, 24,9 %) et l'acétaminophène (n = 329, 21,9 %); les opioïdes (n = 594, 48,1 %) étaient les plus répandus parmi les 1236 intoxications non intentionnelles. Dans 716 des cas (24,0 %), le patient a été admis dans les services de soins aigus. Le taux de mortalité hospitalière était de 1,0 % (n = 31). Par ailleurs, 111 patients (9,0 %) présentant une intoxication médicamenteuse non intentionnelle ont quitté l'hôpital contre avis médical. Enfin, dans 772 des cas d'intoxication (25,9 %), le patient est retourné à l'urgence après sa sortie à cause d'une intoxication médicamenteuse ultérieure. Conclusions: Les intoxications médicamenteuses sont une cause fréquente de visites dans les SU urbains. Ils sont rarement mortels, mais sont associés à une utilisation importante des ressources hospitalières et à une récidive considérable.

Improving medication prescribing-related outcomes for vulnerable elderly in transitions on high-risk medications (IMPROVE-IT HRM): a pilot randomized trial protocol.

BACKGROUND: Seniors with recurrent hospitalizations who are taking multiple medications including high-risk medications are at particular risk for serious adverse medication events. We will assess whether an expert Clinical Pharmacology and Toxicology (CPT) medication management intervention during hospitalization with follow-up post-discharge and communication with circle of care is feasible and can decrease drug therapy problems amongst this group. METHODS: The design is a pragmatic pilot randomized trial with 1:1 patient-level concealed randomization with blinded outcome assessment and data analysis. Participants will be adults 65 years and older admitted to internal medicine services for more than 2 days, who have had at least one other hospitalization in the prior year, taking five or more chronic medications including at least one high-risk medication. The CPT intervention identifies medication targets; completes consult, including priorities for improving prescribing negotiated with the patient; starts the care plan; ensures a detailed discharge medication reconciliation and circle-of-care communication; and sees the patient at least twice after hospital discharge via virtual visits to consolidate the care plan in the community. Control group receives usual care. Primary outcomes are feasibility - recruitment, retention, costs, and clinical - number of drug therapy problems improved, with secondary outcomes examining coordination of transitions in care, quality of life, and healthcare utilization and costs. Follow-up is to 3-month posthospital discharge. DISCUSSION: If results support feasibility of ramp-up and promising clinical outcomes, a follow-up definitive trial will be organized using a developing national platform and medication appropriateness network. Since the intervention allows a very scarce medical specialty expertise to be offered via virtual care, there is potential to improve the safety, outcomes, and cost of care widely. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04077281.

Thrombopoietin Receptor Agonists and Other Second-Line Therapies for Immune Thrombocytopenia: A Narrative Review With a Focus on Drug Access in Canada.

INTRODUCTION: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet counts and increased risk of bleeding. After corticosteroids with or without intravenous immune globulin (first-line treatment), second-line treatment options include rituximab, splenectomy, thrombopoietin receptor agonists (TPO-RAs), and fostamatinib. In Canada, the choice of second-line therapy is influenced by access to medications. The goals of this narrative review are to 1) summarize the evidence for the use of TPO-RAs and other second-line therapies in ITP and 2) highlight differences in public funding criteria for TPO-RAs across provinces and territories in Canada. METHODS: We conducted a literature review of second-line therapies for ITP. We solicited information on public funding programs for TPO-RAs in Canada from health care providers, pharmacists, and provincial ministries of health. RESULTS: Head-to-head trials involving TPO-RAs, rituximab, splenectomy, and fostamatinib are lacking. There is substantial evidence of effect for TPO-RAs in improving platelet count levels, health-related quality of life, bleeding, and fatigue from placebo-controlled trials and observational studies; however, access to TPO-RAs through provincial funding programs in Canada is variable. Splenectomy failure is a prerequisite for the funding of TPO-RAs in Ontario, Manitoba, and Saskatchewan, but not in Alberta or Quebec. Other provinces either do not have access to public funding or funding is provided on a case-by-case basis. DISCUSSION: TPO-RAs are effective second-line therapies for the treatment of ITP; however, access is variable across Canada, which results in health disparities and poor uptake of international treatment guidelines.

Developing a reporting item checklist for studies of HIV drug resistance prevalence or incidence: a mixed methods study.

BACKGROUND: Adequate surveillance of HIV drug resistance prevalence is challenged by heterogenous and inadequate data reporting. To address this issue, we recently published reporting guidance documentation for studies of HIV drug resistance prevalence and incidence. OBJECTIVES: In this study, we describe the methods used to develop this reporting guidance. DESIGN: We used a mixed-methods sequential explanatory design involving authors and users of studies of HIV drug resistance prevalence. In the quantitative phase, we conducted a cross-sectional electronic survey (n=51). Survey participants rated various reporting items on whether they are essential to report. Validity ratios were computed to determine the items to discuss in the qualitative phase. In the qualitative phase, two focus group discussions (n=9 in total) discussed this draft item checklist, providing a justification and examples for each item. We conducted a descriptive qualitative analysis of the group discussions to identify emergent themes regarding the qualities of an essential reporting item. RESULTS: We identified 38 potential reporting items that better characterise the study participants, improve the interpretability of study results and clarify the methods used for HIV resistance testing. These items were synthesised to create the reporting item checklist. Qualitative insights formed the basis of the explanation, elaboration, and rationale components of the guidance document. CONCLUSIONS: We generated a list of reporting items for studies on the incidence or prevalence of HIV drug resistance along with an explanation of why researchers believe these items are important. Mixed methods allowed for the simultaneous generation and integration of the item list and qualitative insights. The integrated findings were then further developed to become the subsequently published reporting guidance.

Hydroxychloroquine-Chloroquine, QT-Prolongation, and Major Adverse Cardiac Events: A Meta-analysis and Scoping Review.

OBJECTIVES: We aimed to evaluate the high-quality literature on the frequency and nature of major adverse cardiac events (MACE) associated with either hydroxychloroquine (HCQ) or chloroquine (CQ). DATA SOURCES: We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onward using search strategies created in collaboration with medical science librarians. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials (RCTs) published in English language from January 1996 to September 2022, involving adult patients at least 18 years of age, were selected. Outcomes of interest were death, arrhythmias, syncope, and seizures. Random-effects meta-analyses were performed with a Treatment Arm Continuity Correction for single and double zero event studies. DATA SYNTHESIS: By study drug, there were 31 HCQ RCTs (n = 6677), 9 CQ RCTs (n = 622), and 1 combined HCQ-CQ trial (n = 105). Mortality was the most commonly reported MACE at 220 of 255 events (86.3%), with no reports of torsades de pointes or sudden cardiac death. There was no increased risk of MACE with exposure to HCQ-CQ compared with control (risk ratio [RR] = 0.90, 95% CI = 0.69-1.17, I2 = 0%). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: These findings have important implications with respect to patient reassurance and updated guidance for prescribing practices of these medications. CONCLUSIONS: Despite listing as QT-prolonging meds, HCQ-CQ did not increase the risk of MACE.

Genotype-guided drug prescribing vs. usual care reduced clinically relevant adverse drug reactions at 12 wk.

SOURCE CITATION: Swen JJ, van der Wouden CH, Manson LE, et al; Ubiquitous Pharmacogenetics Consortium. A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study. Lancet. 2023;401:347-356. 36739136.

Team approach to polypharmacy evaluation and reduction: feasibility randomized trial of a structured clinical pathway to reduce polypharmacy.

BACKGROUND: Polypharmacy is associated with poorer health outcomes in older adults. Other than the associated multimorbidity, factors contributing to this association could include medication adverse effects and interactions, difficulties in managing complicated medication regimes, and reduced medication adherence. It is unknown how reversible these negative associations may be if polypharmacy is reduced. The purpose of this study was to determine the feasibility of implementing an operationalized clinical pathway aimed to reduce polypharmacy in primary care and to pilot measurement tools suitable for assessing change in health outcomes in a larger randomized controlled trial (RCT). METHODS: We randomized consenting patients ≥ 70 years old on ≥ 5 long-term medications into intervention or control groups. We collected baseline demographic information and research outcome measures at baseline and 6 months. We assessed four categories of feasibility outcomes: process, resource, management, and scientific. The intervention group received TAPER (team approach to polypharmacy evaluation and reduction), a clinical pathway for reducing polypharmacy using "pause and monitor" drug holiday approach. TAPER integrates patients' goals, priorities, and preferences with an evidence-based "machine screen" to identify potentially problematic medications and support a tapering and monitoring process, all supported by a web-based system, TaperMD. Patients met with a clinical pharmacist and then with their family physician to finalize a plan for optimization of medications using TaperMD. The control group received usual care and were offered TAPER after follow-up at 6 months. RESULTS: All 9 criteria for feasibility were met across the 4 feasibility outcome domains. Of 85 patients screened for eligibility, 39 eligible patients were recruited and randomized; two were excluded post hoc for not meeting the age requirement. Withdrawals (2) and losses to follow-up (3) were small and evenly distributed between arms. Areas for intervention and research process improvement were identified. In general, outcome measures performed well and appeared suitable for assessing change in a larger RCT. CONCLUSIONS: Results from this feasibility study indicate that TAPER as a clinical pathway is feasible to implement in a primary care team setting and in an RCT research framework. Outcome trends suggest effectiveness. A large-scale RCT will be conducted to investigate the effectiveness of TAPER on reducing polypharmacy and improving health outcomes. TRIAL REGISTRATION: clinicaltrials.gov NCT02562352 , Registered September 29, 2015.

Comparability of Objective Structured Clinical Examinations (OSCEs) and Written Tests for Assessing Medical School Students' Competencies: A Scoping Review.

Objective Structured Clinical Examinations (OSCEs) and written tests are commonly used to assess health professional students, but it remains unclear whether the additional human resources and expenses required for OSCEs, both in-person and online, are worthwhile for assessing competencies. This scoping review summarized literature identified by searching MEDLINE and EMBASE comparing 1) OSCEs and written tests and 2) in-person and online OSCEs, for assessing health professional trainees' competencies. For Q1, 21 studies satisfied inclusion criteria. The most examined health profession was medical trainees (19, 90.5%), the comparison was most frequently OSCEs versus multiple-choice questions (MCQs) (18, 85.7%), and 18 (87.5%) examined the same competency domain. Most (77.5%) total score correlation coefficients between testing methods were weak (r < 0.40). For Q2, 13 articles were included. In-person and online OSCEs were most used for medical trainees (9, 69.2%), checklists were the most prevalent evaluation scheme (7, 63.6%), and 14/17 overall score comparisons were not statistically significantly different. Generally low correlations exist between MCQ and OSCE scores, providing insufficient evidence as to whether OSCEs provide sufficient value to be worth their additional cost. Online OSCEs may be a viable alternative to in-person OSCEs for certain competencies where technical challenges can be met.

Thromboembolic Events in Users of Warfarin Treated with Different Skeletal Muscle Relaxants.

Background and Objectives: Warfarin and a skeletal muscle relaxant are co-treatments in nearly a quarter-million annual United States (US) office visits. Despite international calls to minimize patient harm arising from anticoagulant drug interactions, scant data exist on clinical outcomes in real-world populations. We examined effects of concomitant use of warfarin and individual muscle relaxants on rates of hospitalization for thromboembolism among economically disadvantaged persons. Materials and Methods: Using 1999−2012 administrative data of four US state Medicaid programs, we conducted 16 retrospective self-controlled case series studies: half included concomitant users of warfarin + one of eight muscle relaxants; half included concomitant users of an inhaled corticosteroid (ICS) + one of eight muscle relaxants. The ICS analyses served as negative control comparisons. In each study, we calculated incidence rate ratios (IRRs) comparing thromboembolism rates in the co-exposed versus warfarin/ICS-only exposed person-time, adjusting for time-varying confounders. Results: Among ~70 million persons, we identified 8693 warfarin-treated subjects who concomitantly used a muscle relaxant, were hospitalized for thromboembolism, and met all other inclusion criteria. Time-varying confounder-adjusted IRRs ranged from 0.31 (95% confidence interval: 0.13−0.77) for metaxalone to 3.44 (95% confidence interval: 1.53−7.78) for tizanidine. The tizanidine finding was robust after quantitatively adjusting for negative control ICS findings, and in numerous prespecified secondary analyses. Conclusions: We identified a potential >3-fold increase in the rate of hospitalized thromboembolism in concomitant users of warfarin + tizanidine vs. warfarin alone. Alternative explanations for this finding include confounding by indication, a native effect of tizanidine, or chance.

The impact of OHIP+ pharmacare on use and costs of public drug plans among children and youth in Ontario: a time-series analysis.

BACKGROUND: In 2018, Ontario implemented a pharmacare program (Ontario Health Insurance Plan Plus [OHIP+]) to provide children and youth younger than 25 years with full coverage for prescription medications in the provincial formulary. We aimed to assess the use of public drug plans and costs of publicly covered prescriptions before and after the program's implementation and modification. METHODS: We conducted a population-based, interrupted time-series analysis using data on prescription drug claims, from the Canadian Institute for Health Information's National Prescription Drug Utilization Information System, for people younger than 25 years from January 2016 to October 2019 in Ontario, using British Columbia as the control. We assessed changes in the level and trend of publicly covered prescriptions and expenditures after the introduction of OHIP+ in January 2018 and after program modifications in April 2019. We also assessed plan use and expenditures for publicly covered prescriptions for diabetes and asthma. RESULTS: Publicly covered prescriptions in Ontario increased by 290%, from 756 per 1000 people before OHIP+ to 2952 per 1000 (p < 0.001) after its implementation. After program modification, prescriptions decreased by 52% to 1421 per 1000 (p < 0.001). Similarly, total public drug expenditures increased by 254%, from $379 million in 2017 to $839 million in 2018, then reduced by 49% to $204 million in 2019. Monthly public plan expenditures increased by $115.94 (95% confidence interval [CI] $100.93 to $130.94) post-OHIP+ implementation and decreased by $99.97 (95% CI -$119.79 to -$80.15) per person per month after April 2019. INTERPRETATION: Adopting OHIP+ increased use of public drug plans and expenditures for publicly funded prescription medicines, and the program modification was associated with decreases in both outcomes. This study's findings can inform the national pharmacare debate; future research should investigate associations with health outcomes.

Trajectories of systemic agent use and associated depression- and anxiety-related health care costs among patients with psoriasis.

Background: Systemic treatment patterns and related mental health disorders and economic burden among patients with psoriasis are largely unknown. Objective: To assess systemic treatment patterns and associated depression and anxiety-related health care costs among patients with psoriasis initiating a conventional systemic treatment (CST). Methods: Using a retrospective cohort design with sequence and cluster analyses, we assessed systemic treatment trajectories (CST and tumor necrosis factor inhibitors or ustekinumab, [TNFi/UST]) over a 2-year period following CST initiation. We compared health care costs between trajectories using 2-part models. Results: We included 781 patients and identified 8 trajectories: persistent methotrexate users, persistent acitretin users, early CST discontinuation, late methotrexate discontinuation, switch to TNFi/UST, adding TNFi/UST, discontinuation then restart on methotrexate, and discontinuation then restart on acitretin or multiple CST switches. Overall, 165 (21%) patients incurred depression- and anxiety-related health care costs (median annual cost, CAN$56; quartiles, $14-$127). Compared with persistent methotrexate users, adding a TNFi/UST (cost ratio, 3.63; 95% CI, 1.47-5.97) and discontinuation then restart on acitretin or multiple switches between systemic agents (cost ratio, 13.3; 95% CI 5.76-22.47) had higher costs. Limitations: Trajectory misclassification may have occured. These date represent an association, and causality cannot be inferred, particularly given the risk of confounding. Conclusion: Depression- and anxiety-related health care costs were high among patients adding TNFi/UST and those discontinuing then restarting on acitretin or experiencing multiple switches between systemic agents.

Coordination of Oral Anticoagulant Care at Hospital Discharge (COACHeD): protocol for a pilot randomised controlled trial.

BACKGROUND: Oral anticoagulants (OACs) are commonly prescribed, have well-documented benefits for important clinical outcomes but have serious harms as well. Rates of OAC-related adverse events including thromboembolic and hemorrhagic events are especially high shortly after hospital discharge. Expert OAC management involving virtual care is a research priority given its potential to reach remote communities in a more feasible, timely, and less costly way than in-person care. Our objective is to test whether a focused, expert medication management intervention using a mix of in-person consultation and virtual care follow-up, is feasible and effective in preventing anticoagulation-related adverse events, for patients transitioning from hospital to home. METHODS AND ANALYSIS: A randomized, parallel, multicenter design enrolling consenting adult patients or the caregivers of cognitively impaired patients about to be discharged from medical wards with a discharge prescription for an OAC. The interdisciplinary multimodal intervention is led by a clinical pharmacologist and includes a detailed discharge medication reconciliation and management plan focused on oral anticoagulants at hospital discharge; a circle of care handover and coordination with patient, hospital team and community providers; and early post-discharge follow-up virtual medication check-up visits at 24 h, 1 week, and 1 month. The control group will receive usual care plus encouragement to use the Thrombosis Canada website. The primary feasibility outcomes include recruitment rate, participant retention rates, trial resources management, and the secondary clinical outcomes include adverse anticoagulant safety events composite (AASE), coordination and continuity of care, medication-related problems, quality of life, and healthcare resource utilization. Follow-up is 3 months. DISCUSSION: This pilot RCT tests whether there is sufficient feasibility and merit in coordinating oral anticoagulant care early post-hospital discharge to warrant a full sized RCT. TRIAL REGISTRATION: NCT02777047.

Potentially Inappropriate Prescribing in Hospitalized Older Adult High-Cost Health Care Users: A Pilot Study.

Background: High-cost health care users use disproportionate amounts of health care resources relative to the typical patient. It is unclear to what extent poor-quality prescribing, including potentially inappropriate prescribing (PIP), may be contributing to their adverse outcomes and health utilization costs. Objectives: To evaluate the prevalence of PIP and to explore its impact in older adult high-cost health care users. Methods: The charts of older adult high-cost health care users admitted to 2 academic hospitals in Ontario, Canada, in fiscal year 2015/16 were reviewed. Eligible patients were at least 66 years old with at least 5 emergency department visits and 3 hospital admissions in the previous year. A total of 243 patients met these criteria, of whom 100 were randomly selected for review. Cases of PIP were identified using explicit prescribing quality indicators, including the STOPP/START criteria. Types of PIP included potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs). Log-linear regression was used to characterize the relationship between PIP and future health care utilization. Medications were reconciled to determine the proportion of PIP addressed by the time of discharge. Results: Eighty-nine of the 100 patients had at least 1 instance of PIP. In total, 276 PIMs and 54 PPOs were identified. Of the 271 instances of PIP identified on admission, only 38 (14%) were resolved by the time of hospital discharge. Each additional PPO was associated with a 1.43-fold increase in the rate of future emergency department visits (p < 0.001). Conclusions: The rate of PIP among older adult high-cost health care users was high. Despite frequent interactions with the health care system, many opportunities to improve the quality of prescribing for this vulnerable population were missed. Greater attention to medication optimization is needed.

Contexte: Les grands utilisateurs de soins de santé consomment une proportion disproportionnée des ressources par rapport aux patients moyens. On ne sait pas vraiment dans quelle mesure la prescription de mauvaise qualité, notamment la prescription potentiellement inappropriée (PPI), contribue aux effets indésirables et aux coûts d'utilisation des soins de santé. Objectifs: Évaluer la prévalence des PPI et étudier ses effets chez les grands utilisateurs des soins de santé âgés. Méthodes: Les dossiers des grands utilisateurs de soins de santé âgés admis dans 2 hôpitaux universitaires en Ontario, au Canada, pendant l'exercice 2015­2016 ont été examinés. Les patients admissibles étaient âgés d'au moins 66 ans, avaient effectué au moins 5 visites à l'urgence et avaient été admis 3 fois à l'hôpital au cours de l'année précédente. Au total, 243 patients répondaient à ces critères, dont 100 ont été sélectionnés au hasard pour un examen. Les cas de PPI ont été identifiés à l'aide d'indicateurs explicites de la qualité de prescription, notamment les critères STOPP/START. Les types de PPI comprenaient des médicaments potentiellement inappropriés (MPI) et les omissions potentielles de prescription (OPP). La régression log-linéaire a été utilisée pour caractériser la relation entre la PPI et l'utilisation future des soins de santé. Un bilan comparatif des médicaments prescrits a été effectué pour déterminer la proportion de PPI traités au moment de la sortie de l'hôpital. Résultats: Quatre-vingt-neuf (89 %) des patients présentaient au moins 1 cas de PPI. Au total, 276 MPI et 54 OPP ont été identifiées. Sur les 271 cas de PPI identifiés au moment de l'admission, seuls 38 (14 %) étaient résolus au moment de la sortie de l'hôpital. Chaque OPP supplémentaire était associée à une augmentation de 1,43 fois du taux de futures visites à l'urgence (p < 0,001). Conclusions: Le taux de PPI chez les grands utilisateurs de soins de santé âgés était élevé. Malgré des interactions fréquentes avec le système de santé, de nombreuses occasions d'amélioration de la qualité des prescriptions pour cette population vulnérable ont été manquées. Une plus grande attention doit être portée à l'optimisation des médicaments.

Dexmedetomidine vs other sedatives in critically ill mechanically ventilated adults: a systematic review and meta-analysis of randomized trials.

Conventional gabaminergic sedatives such as benzodiazepines and propofol are commonly used in mechanically ventilated patients in the intensive care unit (ICU). Dexmedetomidine is an alternative sedative that may achieve lighter sedation, reduce delirium, and provide analgesia. Our objective was to perform a comprehensive systematic review summarizing the large body of evidence, determining if dexmedetomidine reduces delirium compared to conventional sedatives. We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov and the WHO ICTRP from inception to October 2021. Independent pairs of reviewers identified randomized clinical trials comparing dexmedetomidine to other sedatives for mechanically ventilated adults in the ICU. We conducted meta-analyses using random-effects models. The results were reported as relative risks (RRs) for binary outcomes and mean differences (MDs) for continuous outcomes, with corresponding 95% confidence intervals (CIs). In total, 77 randomized trials (n = 11,997) were included. Compared to other sedatives, dexmedetomidine reduced the risk of delirium (RR 0.67, 95% CI 0.55 to 0.81; moderate certainty), the duration of mechanical ventilation (MD - 1.8 h, 95% CI - 2.89 to - 0.71; low certainty), and ICU length of stay (MD - 0.32 days, 95% CI - 0.42 to - 0.22; low certainty). Dexmedetomidine use increased the risk of bradycardia (RR 2.39, 95% CI 1.82 to 3.13; moderate certainty) and hypotension (RR 1.32, 95% CI 1.07 to 1.63; low certainty). In mechanically ventilated adults, the use of dexmedetomidine compared to other sedatives, resulted in a lower risk of delirium, and a modest reduction in duration of mechanical ventilation and ICU stay, but increased the risks of bradycardia and hypotension.

Association of direct oral anticoagulant-proton pump inhibitor cotherapy with adverse outcomes: protocol for a population-based cohort study.

INTRODUCTION: Proton pump inhibitors (PPIs) are widely used for primary and secondary prevention of upper gastrointestinal bleeding. However, there remains controversy about the overall net clinical benefit of PPIs (omeprazole, rabeprazole, pantoprazole, lansoprazole) when coprescribed with direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, edoxaban). Our objective is to explore the risk of clinically relevant events, including bleeding, thromboembolic events and death, in patients prescribed DOACs while taking PPIs versus no PPI. METHODS AND ANALYSIS: The protocol describes a retrospective cohort study of all Ontario residents aged 66 years or older with atrial fibrillation and at least one pharmacy dispensation for a DOAC identified using linked administrative healthcare databases covering 2009-2020. Ontario drug benefit dispensation records will be used to ascertain PPI exposure during DOAC therapy. The primary outcome is a composite of clinically relevant bleeding, thrombotic events or all-cause death. A minimum of 520 patients in total with at least one of the components of the composite outcome are needed. Poisson regression with a generalised estimating equation model will be used to calculate the adjusted incidence rate difference, incidence rate ratios 95% CI, adjusting for propensity for PPI use using inverse probability of treatment weights. ETHICS AND DISSEMINATION: This research is exempt from REB review under section 45 of Ontario's Personal Health Information Protection Act. We will report our findings in a peer-reviewed biomedical journal and present them at conferences. The study will provide useful evidence to optimise the coprescription of DOACs and PPIs in practice.

Software Architecture for Automated Assessment of Prescription Writing.

Prescribing skills are a crucial competency in medical practice considering the increasing numbers of medications available and the increasingly complex patients with multiple diseases faced in clinical practice. Medical students need to become proficient in these skills during training, as required by medical licensing colleges. Not only is teaching the fundamentals of safe and cost-effective prescribing to medical students challenging but evaluating their prescribing skills by faculty members is difficult and time consuming. The COVID-19 pandemic has accelerated the interest in clinically relevant online exams, including automated assessment of short answer style questions. The goal of this project was to design a software to automate the assessment of learners' prescriptions written during low stakes formative assessments. After establishing the components of a legal prescription with multiple medications, and identifying the sources of errors in prescribing and prescribing assessment, we designed and validated an architecture and developed a prototype for automated parsing of learner prescriptions.

Sex Differences in the Patterns of Systemic Agent use Among Patients With Psoriasis: A Retrospective Cohort Study in Quebec, Canada.

Background: Sex differences exist in psoriasis manifestation and expectations from treatment with systemic agents, including, conventional systemic agents (CSA) and tumor necrosis factor inhibitors or ustekinumab (TNFi/UST). However, sex differences in patterns of systemic agent use, such as CSA discontinuation and switch from CSA to TNFi/UST have not been examined. Objectives: To assess sex differences in patterns of CSA use and identify factors associated with switch to (or add) a TNFi/UST and those associated with CSA discontinuation. Methods: We conducted a retrospective cohort study using the Quebec health administrative databases. We included patients with psoriasis initiating a CSA in 2002-2015. We excluded patients with a psoriasis diagnosis in the 3 years prior to the first diagnosis date between 2002 and 2015, and those with a systemic agent dispensation in the year prior to that date. We used Cox regression models with the Least Absolute Shrinkage and Selection Operator method to identify factors associated with Switch/add TNFi/UST, and those associated with CSA discontinuation. Separate analyses were performed for male and female patients. Results: We included 1,644 patients (55.7% females, mean age 60.3 years), among whom 60.4% discontinued their CSA and 7.4%, switched/added TNFi/UST (3.4% switched and 4.0% added) within a median of 0.78 years of follow-up. Among male and female patients, rates of Switch/add TNFi/UST per 1,000 person-year were 49.1 and 41.0 and rates of CSA discontinuation were 381.2 and 352.8. Clinical obesity in male patients (HR 3.53, 95% CI 1.20-10.35), and adjustment/somatoform/dissociative disorders (HR 3.17, 95% CI 1.28-7.85) and use of nonsteroidal anti-inflammatory drugs (HR 2.70, 95% CI 1.56-4.70) in female patients were associated with Switch/add TNFi/UST. Male patients followed by a rheumatologist (HR 0.66, 95% CI 0.46-0.94) and those with a prior hospitalization (HR 0.70, 95% CI 0.57-0.87) were at lower risk of CSA discontinuation, while those initiated on acitretin (vs methotrexate) were at higher risk to discontinue their CSA (HR 1.61, 95% CI 1.30-2.01). Female patients with rheumatoid arthritis comorbidity (HR 0.69, 95% CI 0.51-0.93), those with a dispensed lipid-lowering agent (HR 0.72, 95% CI 0.59-0.88) and hypoglycemic agent (HR 0.75, 95% CI 0.57-0.98) and those initiated on methotrexate (vs all other CSAs) were less likely to discontinue their CSA. Male and female patients entering the cohort between 2011 and 2015 were at reduced risk of CSA discontinuation compared to those entering the cohort before 2011. Conclusion: Most male and female patients discontinued their CSA within 1 year of follow-up. Our study highlighted sex differences in patients' characteristics associated with switch/add a TNFi/UST and CSA discontinuation; treatment switch and discontinuation may be indications of treatment failure in most patients.

Variability in prescription medication coverage for children and youth across Canada: A scoping review.

BACKGROUND: Prescription medication coverage in Canada is provided by at least 14 public drug plans and thousands of private insurance plans. Previous literature suggests that public plan coverage varies, and little is known about private drug plans. OBJECTIVE: Undertake a scoping review of recent literature evaluating coverage of prescription medication for children and youth under 25 across Canada. METHODS: Bibliographic databases (Embase, CINAHL, Web of Science, Medline) and gray literature sources were screened. Papers published between January 2005 and July 2021, focusing on prescription medication coverage for Canadians under 25 years were identified. RESULTS: Of 562 titles and abstracts, 9 reports met our criteria. One report estimates 3.3% of children and youth in 10 provinces are uninsured (i.e. not eligible), with non-enrollment for those eligible for public plans ranging from 12% to 49%. Minimal information on private drug plan coverage was identified. Demographic- or income-based public drug plans report coverage in 12 of 14 jurisdictions. Those covered by a demographic- or income-based plan have access to jurisdictional formularies. 3 of 14 public plans report no cost sharing for children. CONCLUSION: There is less variability in who and what is covered and more in how much is covered (i.e., details of cost sharing). More research is needed to adequately understand the gaps in coverage and its impact on children and youth.