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.

In healthy older adults, daily aspirin increased cancer mortality.

SOURCE CITATION: McNeil JJ, Gibbs P, Orchard SG, et al. Effect of aspirin on cancer incidence and mortality in older adults. J Natl Cancer Inst. 2021;113:258-65. 32778876.

USPSTF recommends asking adults screening questions about unhealthy drug use.

SOURCE CITATION: Krist AH, Davidson KW, Mangione CM, et al. Screening for unhealthy drug use: US Preventive Services Task Force recommendation statement. JAMA. 2020;323:2301-09. 32515821.

Evaluation of online clinical pharmacology curriculum resources for medical students.

AIMS: To identify and evaluate clinical pharmacology (CP) online curricular (e-Learning) resources that are internationally available for medical students. METHODS: Literature searches of Medline, EMBASE and ERIC databases and an online survey of faculty members of international English language medical schools, were used to identify CP e-Learning resources. Resources that were accessible online in English and aimed to improve the quality of prescribing specific medications were then evaluated using a summary percentage score for comprehensiveness, usability and quality, and for content suitability. RESULTS: Our literature searches and survey of 252 faculty (40.7% response rate) in 219 medical schools identified 22 and 59 resources respectively. After screening and removing duplicates, 8 eligible resources remained for evaluation. Mean total score was 53% (standard deviation = 13). The Australian National Prescribing Curriculum, ranked highest with a score of 77%, based primarily on very good ratings for usability, quality and suitable content. CONCLUSION: Using a novel method and evaluation metric to identify, classify, and rate English language CP e-Learning resources, the National Prescribing Curriculum was the highest ranked open access resource. Future work is required to implement and evaluate its effectiveness on prescribing competence.

Rates of hemorrhage during warfarin therapy for atrial fibrillation.

BACKGROUND: Although warfarin has been extensively studied in clinical trials, little is known about rates of hemorrhage attributable to its use in routine clinical practice. Our objective was to examine incident hemorrhagic events in a large population-based cohort of patients with atrial fibrillation who were starting treatment with warfarin. METHODS: We conducted a population-based cohort study involving residents of Ontario (age ≥ 66 yr) with atrial fibrillation who started taking warfarin between Apr. 1, 1997, and Mar. 31, 2008. We defined a major hemorrhage as any visit to hospital for hemorrage. We determined crude rates of hemorrhage during warfarin treatment, overall and stratified by CHADS(2) score (congestive heart failure, hypertension, age ≥ 75 yr, diabetes mellitus and prior stroke, transient ischemic attack or thromboembolism). RESULTS: We included 125 195 patients with atrial fibrillation who started treatment with warfarin during the study period. Overall, the rate of hemorrhage was 3.8% (95% confidence interval [CI] 3.8%-3.9%) per person-year. The risk of major hemorrhage was highest during the first 30 days of treatment. During this period, rates of hemorrhage were 11.8% (95% CI 11.1%-12.5%) per person-year in all patients and 16.7% (95% CI 14.3%-19.4%) per person-year among patients with a CHADS(2) scores of 4 or greater. Over the 5-year follow-up, 10 840 patients (8.7%) visited the hospital for hemorrhage; of these patients, 1963 (18.1%) died in hospital or within 7 days of being discharged. INTERPRETATION: In this large cohort of older patients with atrial fibrillation, we found that rates of hemorrhage are highest within the first 30 days of warfarin therapy. These rates are considerably higher than the rates of 1%-3% reported in randomized controlled trials of warfarin therapy. Our study provides timely estimates of warfarin-related adverse events that may be useful to clinicians, patients and policy-makers as new options for treatment become available.

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.

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.

Cost-related medication nonadherence in Canada: a systematic review of prevalence, predictors, and clinical impact.

BACKGROUND: Cost-related nonadherence to medications (CRNA) is common in many countries and thought to be associated with adverse outcomes. The characteristics of CRNA in Canada, with its patchwork coverage of increasingly expensive medications, are unclear. OBJECTIVES: Our objective in this systematic review was to summarize the literature evaluating CRNA in Canada in three domains: prevalence, predictors, and effect on clinical outcomes. METHODS: We searched MEDLINE, Embase, Google Scholar, and the Cochrane Library from 1992 to December 2019 using search terms covering medication adherence, costs, and Canada. Eligible studies, without restriction on design, had to have original data on at least one of the three domains specifically for Canadian participants. Articles were identified and reviewed in duplicate. Risk of bias was assessed using design-specific tools. RESULTS: Twenty-six studies of varying quality (n = 483,065 Canadians) were eligible for inclusion. Sixteen studies reported on the overall prevalence of CRNA, with population-based estimates ranging from 5.1 to 10.2%. Factors predicting CRNA included high out-of-pocket spending, low income or financial flexibility, lack of drug insurance, younger age, and poorer health. A single randomized trial of free essential medications with free delivery in Ontario improved adherence but did not find any change in clinical outcomes at 1 year. CONCLUSION: CRNA affects many Canadians. The estimated percentage depends on the sampling frame, the main predictors tend to be financial, and its association with clinical outcomes in Canada remains unproven.

Transfusion premedication to prevent acute transfusion reactions: a retrospective observational study to assess current practices.

BACKGROUND: The use of premedication to prevent acute transfusion reactions has been estimated to occur in 50% to 80% of transfusions. While this practice has some biologic rationale, few clinical studies have been performed to assess the efficacy of this practice, and the methodologic quality of these studies is variable. The primary objective of this study was to describe current practices regarding transfusion premedication to prevent febrile nonhemolytic transfusion reactions, mild allergic transfusion reactions, and transfusion-associated circulatory overload. STUDY DESIGN AND METHODS: We conducted an observational retrospective chart review of a stratified random sample of 324 transfusions that took place over a 6-month period. Data were abstracted from medical records and then scanned into a database for analysis. We calculated inter- and intraobserver agreement on key abstracted data to estimate assessment error. A two-phase adjudication process was used to determine whether or not medications given before the time of each transfusion were intended as premedications. RESULTS: Of the transfusions sampled, 1.6% (95% confidence interval, 0.4-3.9) were associated with premedication medications to prevent an acute transfusion reaction. Inter- and intraobserver reliability in the abstraction of key data points was good. Good agreement in adjudicator classification of outcomes was achieved only when adjudicators were provided with patient source documents. CONCLUSIONS: Premedication use was infrequent and much less common than previously reported. Improved methods of capturing transfusion premedication, which likely require prospective assessments, are needed for future research studies.

Interventions to improve medication reconciliation in primary care.

OBJECTIVE: To systematically review all primary care intervention studies designed to implement medication reconciliation for effects on medication discrepancies, clinical outcomes, and patient knowledge of their medications. DATA SOURCES: We searched MEDLINE (1988-March 2008); Healthstar (1966-March 2008); CINAHL (1982-March 2008); EMBASE (1980-March 2008); Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Cochrane Methodology Register, and Health Technology Assessments; and unpublished material. No language restrictions were applied. Search terms included medication reconciliation, medication errors, prescribing error, medication systems, adverse drug events, drug utilization review, medication list, medication record, and medications management. STUDY SELECTION AND DATA ABSTRACTION: Randomized controlled trials or before-and-after studies that examined the effect of various interventions on medication discrepancies either in ambulatory settings or at hospital discharge among community-dwelling adults were included. Two reviewers independently assessed studies to determine inclusion. Level of agreement between the reviewers was good, with unweighted Cohen's kappa of 0.71. Two of 3 independent reviewers abstracted data and evaluated validity from included studies. Disagreements between reviewers were resolved by consensus. DATA SYNTHESIS: Four trials met the inclusion criteria. Two before-and-after studies (n = 275) in ambulatory care examining systematic medication reconciliation at each visit produced conflicting results. One study showed a reduction in the proportion of medication discrepancies from 88.5% to 49.1% (OR 0.13; 95% CI 0.07 to 0.21); the other showed no benefit. One randomized controlled trial and one before-and-after study (n = 202) evaluated pharmacist medication review at hospital discharge. Neither showed a benefit. Heterogeneity precluded pooling of studies. All included studies had significant design flaws. CONCLUSIONS: There is no good quality evidence demonstrating the effectiveness of medication reconciliation in the primary care setting. Further research is needed.

Features predicting the success of computerized decision support for prescribing: a systematic review of randomized controlled trials.

BACKGROUND: Computerized decision support systems (CDSS) are believed to have the potential to improve the quality of health care delivery, although results from high quality studies have been mixed. We conducted a systematic review to evaluate whether certain features of prescribing decision support systems (RxCDSS) predict successful implementation, change in provider behaviour, and change in patient outcomes. METHODS: A literature search of Medline, EMBASE, CINAHL and INSPEC databases (earliest entry to June 2008) was conducted to identify randomized controlled trials involving RxCDSS. Each citation was independently assessed by two reviewers for outcomes and 28 predefined system features. Statistical analysis of associations between system features and success of outcomes was planned. RESULTS: Of 4534 citations returned by the search, 41 met the inclusion criteria. Of these, 37 reported successful system implementations, 25 reported success at changing health care provider behaviour, and 5 noted improvements in patient outcomes. A mean of 17 features per study were mentioned. The statistical analysis could not be completed due primarily to the small number of studies and lack of diversity of outcomes. Descriptive analysis did not confirm any feature to be more prevalent in successful trials relative to unsuccessful ones for implementation, provider behaviour or patient outcomes. CONCLUSION: While RxCDSSs have the potential to change health care provider behaviour, very few high quality studies show improvement in patient outcomes. Furthermore, the features of the RxCDSS associated with success (or failure) are poorly described, thus making it difficult for system design and implementation to improve.

Deprescribing benzodiazepine receptor agonists taken for insomnia: a review and key messages from practice guidelines.

Long­term benzodiazepine receptor agonist (BZRA) use for insomnia is common and highly prevalent in adults in all care settings. Evidence syntheses suggest that the therapeutic benefits of benzodiazepines for insomnia are marginal and very short term. On the harm side, BZRAs are associated with daytime sedation and confusion. Long­term use increases the risk of falls, fractures, cognitive impairment, and motor vehicle accidents. An evidence­based clinical practice guideline has been developed to assist with deprescribing BZRAs. This review highlights the rationale for deprescribing BZRAs used for insomnia and summarizes key messages for clinicians from the new BZRA deprescribing guideline and their supporting evidence.

Healthcare resource utilization and costs among patients with direct oral anticoagulant or warfarin-related major bleeding.

INTRODUCTION: Direct oral anticoagulants (DOACs) have expanded the options for antithrombotic therapy. DOAC-related major bleeds are associated with favorable outcomes compared to warfarin in clinical trials and routine practice. However, it is unclear whether management of DOAC-associated major bleeding incurs higher resource utilization and costs. MATERIALS AND METHODS: We screened medical records of patients ≥ 66 years with atrial fibrillation admitted to one of five tertiary care hospitals in Ontario, Canada with a hemorrhage. We abstracted bleeds involving DOACs or warfarin and linked them to administrative databases to capture length of hospital stay, blood product use, procedural interventions, intensive care unit (ICU) utilization and related direct medical costs. To control for confounders, multivariate logistic and linear regressions were used for binary and linear outcomes respectively. RESULTS: Among 19,061 records screened, 1978 (10.4%) cases involving 1632 patients met criteria of oral anticoagulant-associated bleeding. Baseline characteristics between DOAC and warfarin groups were similar. Blood product costs were higher for DOACs (all comparisons DOACs vs. warfarin, $1456 vs. $1109, mean difference $347, 95% CI $185 to $509), but length of stay and ICU use were similar. Mean direct medical costs did not differ ($9217 vs. $10,790, adjusted relative ratio 0.94, 95% CI 0.84-1.05). CONCLUSIONS: Prior to introduction of DOAC-specific reversal agents, resource utilization and medical costs were comparable between DOAC- and warfarin-associated major bleeds, despite marginally higher blood product costs incurred by the former. Resource intensity associated with anticoagulant-related bleeding remains high, and our data provide measures for cost-effectiveness evaluation of emerging DOAC antidotes.

Automated telephone reminder messages can assist electronic diabetes care.

Telephone reminder systems have been used to assist in the treatment of many chronic diseases. However, it is unclear if these systems can increase medication and appointment adherence in patients with diabetes without direct patient-provider telephone contact. We tested the feasibility of using an automated telephone reminder system (ATRS) to deliver reminder messages to 253 adults with diabetes enrolled in a randomized controlled trial. Eighty-four percent of the patients were able to register using voice recognition and at least one reminder was delivered to 95% of registered patients over a period of 7.5 months. None of the demographic features studied predicted a patient's ability to enroll or to receive reminder calls. At the end of the study, 63% of patients indicated that they wished to continue to receive ATRS calls. The level of system use as determined by the number of received reminder calls was not associated with a change in the number of physician visits or diabetes-related laboratory tests during follow-up. The clinical benefits and sustainability of ATRS remain unproven, but our results indicate that an automated reminder system can be effective for providing messages to a large group of older patients with diabetes.

Managing High-Cost Healthcare Users: The International Search for Effective Evidence-Supported Strategies.

High-cost healthcare users (HCUs) are a small proportion of the population who use a disproportionate amount of healthcare resources. Although the phenomenon occurs across the entire age spectrum, older adults represent the majority of HCUs. HCUs have drawn increasing attention internationally from clinicians, health policy-makers, and government administrators. Many experts have suggested that the short- and long-term sustainability of the healthcare system is threatened unless current approaches to the care and healthcare costs of this population are modified. Complex case management and care coordination models are being implemented internationally to address HCUs despite a lack of strong evidence to support their effectiveness in improving clinical outcomes or savings in costs of care. We review what is known about HCUs and the available evidence for the effectiveness of interventions designed to manage their high and costly healthcare use.

Patterns of borrowing to finance out-of-pocket prescription drug costs in Canada: a descriptive analysis.

BACKGROUND: Out-of-pocket drug costs lead many Canadians to engage in cost-related nonadherence to prescription medications, but our understanding of other consequences such as borrowing money remains incomplete. In this descriptive study, we sought to quantify the frequency of borrowing to pay for prescription drugs in Canada and characteristics of Canadians who borrowed money for this purpose. METHODS: In partnership with Statistics Canada, we designed and administered a cross-sectional rapid-response module in the Canadian Community Health Survey administered by telephone to Canadians aged 12 years or more between January and June 2016. We restricted our analyses to participants who responded to the question regarding borrowing money to pay for prescription drugs and used logistic regression to identify characteristics associated with borrowing. RESULTS: A total of 28 091 Canadians responded to the survey (overall response rate 61.8%). The weighted proportion of respondents who reported having borrowed money to pay for prescription drugs in the previous year was 2.5% (95% confidence interval 2.2%-2.8%), an estimated 731 000 Canadians. The odds of borrowing were higher among younger adults, people in poor health and people lacking prescription drug insurance. Other factors associated with increased adjusted odds of borrowing were having 2 or more chronic conditions, low household income and higher out-of-pocket prescription drug costs. INTERPRETATION: Many Canadians reported borrowing money to pay for out-of-pocket prescription drug costs, and borrowing was more prevalent among already vulnerable groups that also report other compensatory behaviours to address challenges in paying for prescription drugs. Future research should investigate policy responses intended to increase equity in access to prescription drugs.

The consequences of patient charges for prescription drugs in Canada: a cross-sectional survey.

BACKGROUND: Many Canadians face substantial out-of-pocket charges for prescription drugs. Prior work suggests that this causes some patients to not take their medications as prescribed; however, we have little understanding of whether charges for prescription medicines lead patients to forego basic needs or to use more health care services. Our study aimed to quantify the consequences of patient charges for medicines in Canada. METHODS: As part of the 2016 Canadian Community Health Survey, we designed and fielded cross-sectional questions to 28 091 Canadians regarding prescription drug affordability, consequent use of health care services and trade-offs with other expenditures. We calculated weighted population estimates and proportions, and used logistic regression to determine which patient characteristics were associated with these behaviours. RESULTS: Overall, 5.5% (95% confidence interval 5.1%-6.0%) of Canadians reported being unable to afford 1 or more drugs in the prior year, representing 8.2% of those with at least 1 prescription. Drugs for mental health conditions were the most commonly reported drug class for cost-related nonadherence. About 303 000 Canadians had additional doctor visits, about 93 000 sought care in the emergency department, and about 26 000 were admitted to hospital at the population level. Many Canadians forewent basic needs such as food (about 730 000 people), heat (about 238 000) and other health care expenses (about 239 000) because of drug costs. These outcomes were more common among females, younger adults, Aboriginal peoples, those with poorer health status, those lacking drug insurance and those with lower income. INTERPRETATION: Out-of-pocket charges for medicines for Canadians are associated with foregoing prescription drugs and other necessities as well as use of additional health care services. Changes to protect vulnerable populations from drug costs might reduce these negative outcomes.

A comprehensive appropriateness of prescribing questionnaire was validated by nominal consensus group.

OBJECTIVE: To develop and validate a comprehensive Appropriateness of Prescribing Evaluation Questionnaire (APEQ) suitable for human and computer use. STUDY DESIGN AND SETTING: This study was part of an ongoing research program examining the effectiveness and cost-effectiveness of computerized prescribing decision support for providers, patients, and drug policy. A nominal group consensus process involved physicians, both primary care physicians and specialists, pharmacists, drug plan managers, patients, patient advocates, and pharmaceutical industry. Structured case scenarios of musculoskeletal problems were used to evaluate APEQ's validity and responsiveness. RESULTS: Seventeen panelists evaluated 72 patient scenarios in two rounds. Their ratings of appropriateness, assessed by ANOVA, showed significant agreement with the experts' scores in the two rounds, which evaluated appropriateness and responsiveness, respectively. Interrater and intrarater agreement was moderate to good. CONCLUSION: This formal assessment suggests that APEQ has reasonable validity, reliability, and responsiveness. Such tools could be very useful in e-prescribing and e-claims reimbursement environments and should be further explored.

Understanding the patient experience of cost-related non-adherence to prescription medications through typology development and application.

Many patients report skipping doses, splitting pills, or not filling prescriptions due to out-of-pocket costs-a phenomenon known as cost-related non-adherence (CRNA). This study investigated CRNA from the patient's perspective, and, to our knowledge, is the first study to undertake a qualitative investigation of CRNA specifically. We report the results from 35 semi-structured interviews conducted in 2014-15 with adults in four Canadian cities across two provinces. We used framework analysis to develop a CRNA typology to characterize major factors in patients' CRNA decisions. Our typology identifies four major components: (1) the insurance reason driving the drug cost, (2) the individual's overall financial flexibility, (3) the burden of drug cost on the individual's budget, and (4) the importance of the drug from the individual's perspective. The first two components set the context for CRNA and the final two components are the drivers for the CRNA decision. We also found four major patterns in CRNA experiences: (1) CRNA in individuals with low financial flexibility occurred for all levels of drug importance and all but the lowest level of cost burden; (2) CRNA for high importance drugs only occurred when the drug cost had a high burden on an individual's budget; (3) CRNA in individuals with more financial flexibility primarily occurred in drugs with medium importance but high or very high cost burdens; and (4) CRNA for low importance drugs occurred at almost all levels of drug cost burden. Our study furthers the understanding of how numerous factors such as income, insurance, and individual preferences combine and interact to influence CRNA and suggests that policy interventions must be multi-faceted or encourage significant insurance redesign to reduce CRNA.