Angiotensin Receptor Blockers and the Risk of Suspected Drug-Induced Liver Injury: A Retrospective Cohort Study Using Electronic Health Record-Based Common Data Model in South Korea.

INTRODUCTION: Angiotensin receptor blockers are widely used antihypertensive drugs in South Korea. In 2021, the Korea Ministry of Food and Drug Safety acknowledged the need for national compensation for a drug-induced liver injury (DILI) after azilsartan use. However, little is known regarding the association between angiotensin receptor blockers and DILI. OBJECTIVE: We conducted a retrospective cohort study in incident users of angiotensin receptor blockers from a common data model database (1 January, 2017-31 December, 2021) to compare the risk of DILI among specific angiotensin receptor blockers against valsartan. METHODS: Patients were assigned to treatment groups at cohort entry based on prescribed angiotensin receptor blockers. Drug-induced liver injury was operationally defined using the International DILI Expert Working Group criteria. Cox regression analyses were conducted to derive hazard ratios and the inverse probability of treatment weighting method was applied. All analyses were performed using R. RESULTS: In total, 229,881 angiotensin receptor blocker users from 20 university hospitals were included. Crude DILI incidence ranged from 15.6 to 82.8 per 1000 person-years in treatment groups, most were cholestatic and of mild severity. Overall, the risk of DILI was significantly lower in olmesartan users than in valsartan users (hazard ratio: 0.73 [95% confidence interval 0.55-0.96]). In monotherapy patients, the risk was significantly higher in azilsartan users than in valsartan users (hazard ratio: 6.55 [95% confidence interval 5.28-8.12]). CONCLUSIONS: We found a significantly higher risk of suspected DILI in patients receiving azilsartan monotherapy compared with valsartan monotherapy. Our findings emphasize the utility of real-world evidence in advancing our understanding of adverse drug reactions in clinical practice.

Impact of a Nationwide Medication History Sharing Program on the Care Process and End-User Experience in a Tertiary Teaching Hospital: Cohort Study and Cross-Sectional Study.

Background: Timely and comprehensive collection of a patient's medication history in the emergency department (ED) is crucial for optimizing health care delivery. The implementation of a medication history sharing program, titled "Patient's In-home Medications at a Glance," in a tertiary teaching hospital aimed to efficiently collect and display nationwide medication histories for patients' initial hospital visits. Objective: As an evaluation was necessary to provide a balanced picture of the program, we aimed to evaluate both care process outcomes and humanistic outcomes encompassing end-user experience of physicians and pharmacists. Methods: We conducted a cohort study and a cross-sectional study to evaluate both outcomes. To evaluate the care process, we measured the time from the first ED assessment to urgent percutaneous coronary intervention (PCI) initiation from electronic health records. To assess end-user experience, we developed a 22-item questionnaire using a 5-point Likert scale, including 5 domains: information quality, system quality, service quality, user satisfaction, and intention to reuse. This questionnaire was validated and distributed to physicians and pharmacists. The Mann-Whiteny U test was used to analyze the PCI initiation time, and structural equation modeling was used to assess factors affecting end-user experience. Results: The time from the first ED assessment to urgent PCI initiation at the ED was significantly decreased using the patient medication history program (mean rank 42.14 min vs 28.72 min; Mann-Whitney U=346; P=.03). A total of 112 physicians and pharmacists participated in the survey. Among the 5 domains, "intention to reuse" received the highest score (mean 4.77, SD 0.37), followed by "user satisfaction" (mean 4.56, SD 0.49), while "service quality" received the lowest score (mean 3.87, SD 0.79). "User satisfaction" was significantly associated with "information quality" and "intention to reuse." Conclusions: Timely and complete retrieval using a medication history-sharing program led to an improved care process by expediting critical decision-making in the ED, thereby contributing to value-based health care delivery in a real-world setting. The experiences of end users, including physicians and pharmacists, indicated satisfaction with the program regarding information quality and their intention to reuse.

Development of machine learning algorithms for scaling-up antibiotic stewardship.

BACKGROUND: Antibiotic stewardship programs (ASP) aim to reduce inappropriate use of antibiotics, but their labor-intensive nature impedes their wide adoption. The present study introduces explainable machine learning (ML) models designed to prioritize inpatients who would benefit most from stewardship interventions. METHODS: A cohort of inpatients who received systemic antibiotics and were monitored by a multidisciplinary ASP team at a tertiary hospital in the Republic of Korea was assembled. Data encompassing over 130,000 patient-days and comprising more than 160 features from multiple domains, including prescription records, laboratory, microbiology results, and patient conditions was collected.Outcome labels were generated using medication administration history: discontinuation, switching from intravenous to oral medication (IV to PO), and early or late de-escalation. The models were trained using Extreme Gradient Boosting (XGB) and light Gradient Boosting Machine (LGBM), with SHapley Additive exPlanations (SHAP) analysis used to explain the model's predictions. RESULTS: The models demonstrated strong discrimination when evaluated on a hold-out test set(AUROC - IV to PO: 0.81, Early de-escalation: 0.78, Late de-escalation: 0.72, Discontinue: 0.80). The models identified 41%, 16%, 22%, and 17% more cases requiring discontinuation, IV to PO, early and late de-escalation, respectively, compared to the conventional length of therapy strategy, given that the same number of patients were reviewed by the ASP team. The SHAP results explain how each model makes their predictions, highlighting a unique set of important features that are well-aligned with the clinical intuitions of the ASP team. CONCLUSIONS: The models are expected to improve the efficiency of ASP activities by prioritizing cases that would benefit from different types of ASP interventions along with detailed explanations.

Association between culture and the preference for, and perceptions of, 11 routes of medicine administration: A survey in 21 countries and regions.

Medicines can be taken by various routes of administration. These can impact the effects and perceptions of medicines. The literature about individuals' preferences for and perceptions of the different routes of administration is sparse, but indicates a potential influence of culture. Our aim was to determine: (i) any association between one's culture and one's preferred route of medicine administration and (ii) individual perceptions of pain, efficacy, speed of action and acceptability when medicines are swallowed or placed in the mouth, under the tongue, in the nose, eye, ear, lungs, rectum, vagina, on the skin, or areinjected. A cross-sectional, questionnaire-based survey of adults was conducted in 21 countries and regions of the world, namely, Tunisia, Ghana, Nigeria, Turkey, Ethiopia, Lebanon, Malta, Brazil, Great Britain, United States, India, Serbia, Romania, Portugal, France, Netherlands, Japan, South Korea, Hong Kong, mainland China and Estonia, using the Inglehart-Welzel cultural map to ensure coverage across all cultures. Participants scored the pain/discomfort, efficacy, speed of onset and acceptability of the different routes of medicine administration and stated their preferred route. Demographic information was collected. A total of 4435 participants took part in the survey. Overall, the oral route was the most preferred route, followed by injection, while the rectal route was the least preferred. While the oral route was the most preferred in all cultures, the percentage of participants selecting this route varied, from 98% in Protestant Europe to 50% in the African-Islamic culture. A multinomial logistic regression model revealed a number of predictors for the preferred route. Injections were favoured in the Baltic, South Asia, Latin America and African-Islamic cultures while dermal administration was favoured in Catholic Europe, Baltic and Latin America cultures. A marked association was found between culture and the preference for, and perceptions of the different routes by which medicines are taken. This applied to even the least favoured routes (vaginal and rectal). Only women were asked about the vaginal route, and our data shows that the vaginal route was slightly more popular than the rectal one.