Adverse Drug Events Research Articles

Views on the Development and Use of a New Digital Adverse Drug Event Reporting Platform in Australia: A Qualitative Study.

Reporting of adverse drug events (ADEs) to regulatory authorities remains low, particularly among consumers. To explore stakeholders' views on the development and use of a digital platform to improve ADE reporting by consumers to the regulatory authority in Australia, i.e., the Therapeutic Goods Administration. A qualitative study was conducted using semi-structured interviews, focus group discussions (FGDs), and co-design workshops with consumers, healthcare professionals (HCPs), and regulators. The interview recordings were transcribed verbatim, coded, and analysed thematically according to the Capability, Opportunity, Motivation, Behaviour model. Findings of the FGDs and co-design workshops were incorporated to enhance and complement the insights gathered from the interviews. A total of 39 participants took part in the study (54 % consumers, 41 % HCPs, and 5 % regulators). Uncovered themes related to ADE reporting in general were: difficulty recognizing ADEs and health literacy, awareness about reporting ADEs (Capability); visibility of ADE reporting, professionals' views on consumer ADE reporting, consumer education (Opportunity); the common good, benefit to the reporter, identifying ADEs worth reporting, and concern about reporting (Motivation). Additional identified themes specific to a new digital platform were: physical abilities (Capability); features that facilitate intuitive use, convenience and accessibility, user experience, integration with existing systems, trust, sharing experiences with others (Opportunity); and concern about using a reporting platform, and feedback loop (Motivation). A cross-section of attitudes and values were obtained regarding ADE reporting in general and a new ADE reporting digital platform for consumers in Australia, which will inform its development, implementation and evaluation.

Comprehensive evaluation of leuprorelin-associated adverse events: insights from FDA adverse event reporting system

ABSTRACT Background Leuprorelin, a gonadotropin-releasing hormone agonist, is widely used to treat hormone-related disorders. This study aims to explore and analyze the safety profile of leuprorelin by examining adverse event reports from the FDA Adverse Event Reporting System (FAERS) database. Methods This study conducted a retrospective pharmacovigilance analysis using FAERS data from Q1 2004 to Q1 2024. Adverse drug events (ADEs) related to leuprorelin were identified and categorized by system organ class and specific adverse events. Statistical methods such as Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) were used to detect safety signals. Results A total of 63,928 ADE reports implicated leuprorelin, with 500 preferred terms and 25 system organ classes showing significant disproportionality. Notable rare ADEs identified were bulbospinal muscular atrophy congenital (n = 26; ROR 1282.72, PRR 1282.52, IC 7.91, EBGM 241.28), follicular cystitis (n = 3; ROR 126.84, PRR 126.84, IC 6.48, EBGM 89.09), and anaplastic meningioma (n = 3; ROR 46.73, PRR 46.73, IC 5.34, EBGM 40.5). Conclusion Most findings were expected, but new signals like follicular cystitis, previously unreported, emerged. Further studies are essential to validate these findings, crucial for clinical monitoring and risk identification of leuprorelin.

Using Multiple Drug Similarity Networks to Promote Adverse Drug Event Detection

Using Multiple Drug Similarity Networks to Promote Adverse Drug Event Detection

Operationalizing an adverse event detection surveillance system to support antimicrobial stewardship activities: perceptions and insights from the SHEA research network.

A surveillance system for measuring patient-level antimicrobial adverse drug events (ADE) may support stewardship activities, however, design and implementation questions remain. In this national survey, stewardship experts favored simple, laboratory-based ADE definitions although there were tensions between feasibility, ability to identify attribution without chart review, and importance of specific ADE.

Evaluation of tolvaptan-associated hepatic disorder using different national pharmacovigilance databases

Tolvaptan-associated hepatic disorder is a rare, but lethal adverse event; however, the precise risk and time of onset remain unclear. This study aimed to characterize the severity, time‑to‑onset, and outcomes of hepatic disorder based on patient age and sex. Patient data were acquired from the Japanese Adverse Drug Event Report database (JADER) and the JAPIC AERS database, which consists of the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) processed by the Japan Pharmaceutical Information Center. Hepatic disorder was classified as severe or nonsevere. Tolvaptan use was associated with hepatic disorder in analyses using the FAERS [Severe hepatic disorder: reporting odds ratio (ROR) 4.93, 95% confidence interval (CI) 4.33‒5.61; information component (IC) 2.11, 95% CI 1.92‒2.29; nonsevere hepatic disorder: ROR 6.78, 95% CI 6.01‒7.65; IC 2.51, 95% CI 2.33‒2.68] and the JADER (severe hepatic disorder: ROR 4.21, 95% CI 3.57‒4.97; IC 1.86, 95% CI 1.63‒2.10; nonsevere hepatic disorder: ROR 4.27, 95% CI 3.68‒4.95; IC 1.83, 95% CI 1.62‒2.04). A time‑to‑onset analysis revealed that the median onset time was significantly longer in patients aged < 60 years compared with patients aged ≥ 60, regardless of the severity (FAERS: severe hepatic disorder 7 vs. 58 days, p < 0.0001; nonsevere hepatic disorder 8 vs. 52.5 days, p < 0.0001; JADER: severe hepatic disorder 9.5 vs. 32 days, p = 0.0017; nonsevere hepatic disorder 9 vs. 89 days, p < 0.0001). Severe outcomes were observed, regardless of the severity of hepatic disorder. Patients should be monitored for liver function based on age to prevent fatal outcomes.

Cardiovascular adverse events and immune-related adverse events associated with PD-1/PD-L1 inhibitors for head and neck squamous cell carcinoma (HNSCC)

While some literature has provided limited information about the potential cardiovascular risk and immune-related adverse events (irAEs) risk associated with PD-1/PD-L1 inhibitors in the treatment of Head and Neck Squamous Cell Carcinoma (HNSCC), the exact relevance is still uncertain. To assess the pharmacovigilance (PV), constituent ratio, severity, and reaction outcomes of major adverse cardiovascular events (MACE) and immune-related adverse events (irAEs) related to PD-1/PD-L1 inhibitors for HNSCC reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). We analyzed reports of cardiovascular adverse events and irAEs associated with drug therapy for HNSCC submitted to FAERS from the 1st quarter 2015 to the 3rd quarter of 2023. Three PD-1/PD-L1 inhibitors were identified: nivolumab, pembrolizumab and durvalumab. Our primary composite endpoint was the PV of MACE and irAEs related to PD-1/PD-L1 inhibitors in the treatment of HNSCC, and the secondary endpoint was PV of other cardiovascular events. The software implemented was STATA 17.0 MP. 19,372 suspected drug-adverse event reports related to drug treatment in patients with HNSCC were identified, of which 916 reports were cardiovascular events, including 555 reports of MACE and 361 reports of other cardiovascular events. The PV signal regarding MACE was detected in durvalumab (PRR = 2.12, 95% CI: 1.24–3.61; χ2 = 7.71; ROR = 2.19, 95% CI: 1.24–3.86; IC = 1.01; IC025 = 0.07) but not in nivolumab and pembrolizumab. The constituent ratio of MACE in all adverse events caused by nivolumab (OR = 0.38, 95% CI: 0.19–0.73) and pembrolizumab (OR = 0.48, 95% CI: 0.23–0.99) was significantly decreased, compared with durvalumab. A PV signal about other cardiovascular events was detected in durvalumab (PRR = 3.04, 95% CI: 1.73–5.31; χ2 = 16.13; ROR = 3.15, 95% CI: 1.74–5.70; IC = 1.46; IC025 = 0.48), but it was not detected in nivolumab or pembrolizumab. The constituent ratio of other cardiovascular events in all adverse events caused by nivolumab (OR = 0.25, 95% CI: 0.13–0.48) and pembrolizumab (OR = 0.40, 95% CI: 0.20–0.80) was significantly decreased, compared with durvalumab. The constituent ratio of other cardiovascular events in all adverse events caused by nivolumab (OR = 0.61, 95% CI: 0.38–0.99) was significantly decreased, compared with pembrolizumab. There were 40 cases of hypertension. A PV signal about hypertension was detected in pembrolizumab (PRR = 3.72, 95% CI: 1.87–7.43; χ2 = 15.99; ROR = 3.75, 95% CI: 1.87–7.51; IC = 1.53, IC025 = 0.45), but it was not detected in nivolumab. The constituent ratio of hypertension in all adverse events caused by nivolumab (OR = 0.09, 95% CI: 0.09–0.39) was significantly decreased, compared with pembrolizumab. There were 737 cases of irAEs. A PV signal about irAEs was detected in nivolumab (PPR = 1.27, 95% CI: 1.05–1.53; χ2 = 6.38; ROR = 1.28, 95% CI: 1.06–1.56; IC = 0.29, IC025 = −0.00) and pembrolizumab (PPR = 2.20, 95% CI: 1.79–2.71; χ2 = 56.55; ROR = 2.31, 95% CI: 1.84–2.88; IC = 1.03; IC025 = 0.68), but it was not detected in durvalumab. The constituent ratio of irAEs in all adverse events caused by nivolumab (OR = 0.58, 95% CI: 0.44–0.76) significantly decreased, compared with pembrolizumab. By comparing the PV signals, constituent ratio, severity, and reaction outcome of the three drugs, we suppose that nivolumab can be used as the safest PD-1/PD-L1 inhibitor for HNSCC.

Sex differences in reporting of statin-associated diabetes mellitus to the US Food and Drug Administration

Abstract Background Statins have been reported to precipitate diabetes mellitus (DM) in some patients. Limited evidence suggests that this occurs in women more frequently than men, but direct comparisons of rates of reporting of statin-associated DM between men and women are lacking. Purpose To determine whether there are sex-specific differences in post-marketing reporting of statin-associated DM. Methods We conducted a retrospective pharmacovigilance analysis of spontaneously reported adverse drug events (ADEs) submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System between January 1997 and September 2023. A Proportional Reporting Ratio (PRR) was used to identify the rate of reported statin-associated DM ADEs relative to the rate of DM ADEs reported with all other medications. We compared signals of disproportionate reporting (SDRs) between men and women using a modified relative odds ratio (ROR). Results During the study period, there were two-fold as many reports of statin-associated DM in women than in men (14,793 versus 7,307, respectively), despite the fact there were only 7% more non-DM statin ADEs reported in women compared to men (512,134 versus 480,849, respectively). Compared to the background rate of reporting for all ADEs (0.6%), statin-induced DM was disproportionally reported for all subjects in aggregate (2.1%, PRR=3.7) as well as for men only (1.5%, PRR=2.4) and for women only (2.9%, PRR=5.3). Significant PRRs for DM were observed with each statin and for all statins collectively (Figure 1). Statins were reported as the primary- or secondary-suspected cause of DM in women with considerably greater frequency than in men (58% versus 29%, respectively). Rates of reporting of statin-associated DM were higher in women than in men for all statins, with the greatest difference being observed with atorvastatin (ROR 3.0), and the lowest difference being observed with rosuvastatin (ROR 1.2) (Figure 1). Conclusions Post-marketing ADE surveillance data suggest a markedly higher rate of incident DM associated with statins than with other medications and a higher rate of reporting of statin-associated DM in women than in men. Future studies should consider sex-moderated mechanisms of statin-associated DM.Figure 1

Adverse event profile of albumin-bound paclitaxel: a real-world pharmacovigilance analysis

BackgroundAbraxane plays a crucial role in the treatment of various types of cancer, despite the considerable attention it has garnered for its adverse drug events (ADEs). Nevertheless, there is currently a significant lack of comprehensive real-world pharmacovigilance studies on the ADEs associated with Abraxane.MethodsWe conducted a retrospective analysis of ADEs associated with Abraxane using data mining from the FAERS database, analyzing data from 2005 to 2023. In a real-world setting, we quantified and visualized the signals of these ADEs using four pharmacovigilance algorithms.ResultsThe FAERS database identified a total of 10,230 adverse event reports associated with Abraxane. The study revealed that Abraxane-related adverse drug events involved 27 system organ classes (SOC), with the strongest signals associated with the lymphatic and hematological systems and hepatobiliary disorders. Additionally, we identified 70 significant Preferred Terms (PT) signals, which included some critical adverse events not highlighted in the product labeling, such as cystoid macular edema. Further analysis of the timing of adverse reactions showed a median onset time of 41 days. Most adverse events (AEs) occurred within the first month of using Abraxane (43.5%), although some were still possible 1 year after treatment (3.5%). Gender-specific analysis indicated that high-risk AEs differed between females (nausea, vomiting, and erythema) and males (febrile neutropenia, disseminated intravascular coagulation, and upper gastrointestinal bleeding).ConclusionThe examined results provide crucial recommendations for optimizing the administration of Abraxane, enhancing its effectiveness, and mitigating potential adverse effects. This knowledge will substantially facilitate the implementation of the substance in clinical settings.

PCSK9 inhibitors in HIV patients with dyslipidemia

Abstract Introduction Cardiovascular disease has become increasingly prevalent in the HIV (human immunodeficiency virus) population. Antiretroviral therapy and HIV itself independently increase the risk of dyslipidemia. While statins are currently the predominant therapy to treat dyslipidemia in HIV patients, drug-drug interactions and adverse drug events can limit their use. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a naturally occurring inhibitor of the LDL-receptor pathway. PCSK9 inhibitors offer an alternative in patients who cannot tolerate or need additional therapy in addition to statin for optimal dyslipidemia management. Purpose The purpose of this study is to compare major adverse cardiovascular events in HIV patients on a PCSK9 inhibitor (evolucumab, alirocumab, inclisiran) vs patients not on a PCSK9 inhibitor. Methods A retrospective cohort study was conducted using electronic medical records from a global federated health research network. The TriNetX network was searched on February 10, 2024, including records from 2020 to 2024. Patients were included based on a diagnosis of HIV status and concomitant dyslipidemia. Patients with HIV and dyslipidemia on a PCSK9 inhibitor were propensity-score matched for age, sex, race, and comorbidities with patients who were not on a PCSK9 inhibitor. The outcomes were mortality, myocardial infarction, heart failure and stroke. Results A total of 485 patients were included in the study. PCSK9 inhibitor use associated with 9% lower odds of all-cause mortality (odds radio, .29; 95% CI, 0.18-0.48; p&amp;lt;.0001). PCSK9 inhibitor use was also associated with 8% lower odds of heart failure (odds radio, .63; 95% CI, 0.47-0.85; p&amp;lt;.0023). No significant associations were noted for myocardial infarction (odds radio, .87; 95% CI, 0.63-1.21; p=0.406) or stroke (odds radio, .67; 95% CI, 0.45-1.01; p=0.052). Conclusion The role of dyslipidemia in HIV is challenging due the complex pathophysiology of HIV. There is an apparent increased risk of cardiovascular disease from the infection itself as well current antiretroviral therapies. While current guidelines recommend the use of statins as first line therapy for dyslipidemia in this population, the drug-drug interaction of statins with ARTs, as well as their side effects, limit their use at times. PCSK9 inhibitors are associated with lower odds of all-cause mortality and heart failure. No significant association was seen for myocardial infarction or stroke. They should be considered as an early intervention alongside statins in HIV patients with dyslipidemia. Further research should be done for the long term safety and tolerance of this therapy as well as cost-effectiveness and access to PCSK9 inhibitors in this population.

Polypharmacy and associated factors in the older population in Germany: Results Gesundheit 65+ study

Abstract Background Polypharmacy, the use of 5 or more medications simultaneously, favors the risk of adverse drug events, drug interactions, potentially inappropriate medication (PIM), hospitalizations, falls, frailty, and mortality. This analysis presents the prevalence of polypharmacy and associated factors in people aged 66+ years living in Germany. Methods Data from the nationally representative Study on Health of Older People in Germany (Gesundheit 65+) conducted between 2021-2023 by the Robert Koch Institute, was analyzed. All medicines used, prescribed and over-the-counter, in the 7 days before the interview were documented and classified into anatomical therapeutic chemical codes. Weighted prevalences and associated factors for polypharmacy are presented. Results 96% of the sample (N = 1,474) took at least 1 medication in the 7 days before the interview. Of these, 39% took up to 4 medications, 39% 5-9 and 22% 10+. The overall prevalence of polypharmacy was 61% (95%CI 58-65%) and was significantly higher in women (64%) than in men (59%). Polypharmacy increased with age, from 52% in the age group 66-74 (53% in men, 51% in women), 66% in the age group 75-84 (63% in men, 69% in women) to 81% in the age group 85 + (72% in men, 86% in women). People with low educational level had a polypharmacy prevalence of 63% (58% in men, 66% in women) compared to 56% (55% in men, 58% in women) in those with high educational level. Severe difficulties in organizing daily medication intake were reported in 1% of people taking up to 4 medicines, in 4% of people taking between 5-9 medicines and in 16% of people taking 10+. The prevalence of PIM increased with the number of medicines used: 13% in 1-4 medicines, 31% in 5-9 medicines, and 53% in 10+ medicines. Conclusions Polypharmacy was more frequent in women, older age groups and in people with low educational level. It was associated with increased difficulty in organizing medication intake and with PIM use. Key messages • Polypharmacy is very common, affecting more women, older age groups, people with a low educational level and is associated with PIM use. • Strategies to promote appropriate medication use are needed.

Safety concerns of paternal drug exposure on fertility, pregnancy and offspring: An analysis based on the FDA adverse event reporting system.

Growing evidence indicates that paternal condition significantly influences pregnancy outcomes and offspring health. However, assessing the safety of paternal drug exposure via randomized controlled trials poses ethical challenges, and relevant clinical studies consume a lot of resources to evaluate only a few drugs. Currently, safety data on paternal drug exposure are scarce. To investigate the impact of paternal drug exposure on fertility, pregnancy outcomes, and offspring health. Data from the FDA adverse event reporting system (FAERS) were analyzed (2010-2022). Disproportionality analyses were used to identify signals of each drug-adverse event pair associated with paternal drug exposure in a different hierarchical manner. Out of the 16,180,533 reports, 3210 were related to paternal exposure, encompassing 7808 concomitant adverse events. Drugs used to treat rheumatoid arthritis, cancer, and infections were primary sources of paternal exposure. Analysis identified 115 signals concerning reproductive health. Notably, the signals of diazepam-small for dates baby and finasteride-cryptorchidism were particularly significant (reporting odds ratio, ROR>800, N>10). Moreover, spontaneous abortion signals occur frequently in biologics for the treatment of immune inflammation; the use of immunosuppressive drugs was associated with the highest number of congenital anomalies, with the strongest signals for belatacept-skeletal dysplasia, and tacrolimus-talipes. Only mycophenolic acid, estrogen and imatinib have signals on male fertility. Anti-tumor agents had high numbers of each reproductive toxicity, with the highest values of trisomy 13 signals associated with etoposide and cisplatin. This is the first research to fully assess the safety of paternal exposure to the majority of medications in terms of reproduction. Clinical and scientific researchers should pay close attention to the list of risk medications included in this study, particularly the following association combinations: biologics used to treat inflammatory diseases-abortion, diazepam-small for date baby, finasteride-cryptorchidism, etoposide and cisplatin-13 trisomy.

Evaluating the Economic Impact of the PedAMINES App in Reducing Medication Errors in Pediatric Emergency Care: Cost-Effectiveness Analysis.

The administration of drugs in pediatric emergency care is a time-consuming process and is associated with a higher occurrence of medication errors compared with adult care. This is attributed to the intricacies of administration, which involve calculating doses based on the child's weight or age. To mitigate the occurrence of adverse drug events (ADEs), the PedAMINES (Pediatric Accurate Medication in Emergency Situations; Geneva University Hospitals) mobile app has been developed. This app offers a step-by-step guide for preparing and administering pediatric drugs during emergency interventions by automating the dose calculation process. Although previous simulation-based randomized controlled trials conducted in emergency care have demonstrated the efficacy of the PedAMINES app in reducing drug administration errors, there is a lack of evidence regarding its economic implications. This study aims to evaluate the cost-effectiveness of implementing the PedAMINES app for 4 emergency drugs: epinephrine, norepinephrine, dopamine, and midazolam. The economic evaluation was conducted by combining hospital data from 2019, previous trial outcomes, information extracted from existing literature, and PedAMINES maintenance costs. The cost per avoided medication error was calculated, along with the number of administrations needed to achieve a positive return on investment. Subsequently, Monte Carlo simulations were used to identify the key parameters contributing to result uncertainty. The study revealed the number of preventable errors per administration for the 4 examined drugs: 0.513 for epinephrine, 0.484 for norepinephrine, 0.500 for dopamine, and 0.671 for midazolam. The cost-effectiveness ratios per ADE prevented were computed as follows: US $4808 for epinephrine, US $9705 for norepinephrine, US $6957 for dopamine, and US $2074 for midazolam. Accounting for the economic impact of ADEs, the analysis estimated that 16 administrations of epinephrine, 17 of norepinephrine and dopamine, and 13 of midazolam would be required to attain a positive return on investment. This corresponds to roughly one-third of the annual administrations at a major university hospital in Switzerland. The primary factors influencing the uncertainty in the estimated cost per ADE include the cost of maintenance of the app, the likelihood of an ADE resulting from an administration error, and the frequency of underdosing in the trial's control group. A dedicated mobile app presents an economically viable solution to alleviate the health and economic burden of drug administration errors in in-hospital pediatric emergency care. The widespread adoption of this app is advocated to pool costs and extend the benefits on a national scale in Switzerland.

Prevalence of medication overload among older people with HIV: a MedSafer study

BackgroundOlder people with HIV (PWH) are at risk of polypharmacy (taking multiple medications). Most medications may be necessary and indicated to manage HIV (e.g., antiretroviral therapy [ART]) and HIV-associated comorbidities. However, some are potentially inappropriate medications (PIMs), defined as causing greater harm than benefit, which leads to medication overload. The objective of this study was to characterize polypharmacy (taking multiple medications) and medication overload (prescription of ≥ 1 PIMs) among older PWH.MethodsThis retrospective study included older PWH (aged ≥ 50 years old) attending the tertiary care HIV clinic at the McGill University Health Centre (Montreal, Canada), from June 2022–June 2023. Patient characteristics, medications, and select laboratory values (e.g., CD4 count, hemoglobin A1C) were entered into the MedSafer software identifying PIMs and classifying them according to risk of adverse drug event. We measured the prevalence of polypharmacy (≥ 5 medications prescribed, both including and excluding ART) and medication overload (≥ 1 PIMs). Multivariable logistic regression identified factors associated with medication overload.ResultsThe study included 100 patients, with a median age of 59 years (IQR = 54–63; range 50–82); 42% female. Polypharmacy affected 89% of patients when including antiretroviral therapy (ART) and 60% when excluding ART. Medication overload was present in 58% of patients, and 37.4% of identified PIMs were classified as high-risk. Polypharmacy was the sole predictor of medication overload.ConclusionOlder PWH are at significant risk of medication overload and receiving higher risk PIMs. Deprescribing PIMs in this population could improve medication appropriateness while reducing the risk of ADEs.

Assessing causality in deprescribing studies: A focus on adverse drug events and adverse drug withdrawal events.

Generating real-world evidence about the effect of medication discontinuation or dose reduction on outcomes, such as reduction of adverse drug effects (ADE; intended benefit) and occurrence of adverse drug withdrawal events (ADWE; unintended harm), is crucial to informing deprescribing decisions. Determining the causal effects of deprescribing is difficult for many reasons, including lack of randomization in real-world study designs and other design and measurement issues that pose threats to internal validity. The inherent challenge is how to identify the effects, both intended benefits and unintended harms, of a new medication stoppage or reduction when implemented in patients with many potential clinical and social risks that may influence the likelihood of deprescribing as well as outcomes. We discuss methodological issues of estimating the effect of medication discontinuation or reduction on risk of ADEs and ADWEs considering: (1) sampling study populations of sufficient size with the potential to demonstrate clinically meaningful and quantifiable outcomes, (2) accurate and appropriately timed measurement of covariates, outcomes, and discontinuation, and (3) statistical approaches to managing confounding and other biases inherent in long-term medication use by individuals with multiple morbidities. Designing rigorous deprescribing studies that address internal validity threats will support evidence generation by improving the ability to assess benefits and harms when the exposure of interest is the absence of a medication. Iterative learnings about data quality, variable definition, variable measurement, and exposure-outcome associations will inform strategies to improve the causal inferences possible in real-world deprescribing studies.

Comparative safety of different antibiotic regimens for the treatment of outpatient community-acquired pneumonia among otherwise healthy adults.

Evidence is limited about the comparative safety of antibiotic regimens for treatment of community-acquired pneumonia (CAP). We compared the risk of adverse drug events (ADEs) associated with antibiotic regimens for CAP treatment among otherwise healthy, non-elderly adults. We conducted an active comparator new-user cohort study (2007-2019) of commercially-insured adults 18-64 years diagnosed with outpatient CAP, evaluated via chest x-ray, and dispensed a same-day CAP-related oral antibiotic regimen. ADE follow-up duration ranged from 2-90 days (e.g., renal failure [14 days]). We estimated risk differences [RD] per 100 treatment episodes and risk ratios using propensity score weighted Kaplan-Meier functions. Ankle/knee sprain and influenza vaccination were considered as negative control outcomes. Of 145,137 otherwise healthy CAP patients without comorbidities, 52% received narrow-spectrum regimens (44% macrolide, 8% doxycycline) and 48% received broad-spectrum regimens (39% fluoroquinolone, 7% β-lactam, 3% β-lactam + macrolide). Compared to macrolide monotherapy, each broad-spectrum antibiotic regimen was associated with increased risk of several ADEs (e.g., β-lactam: nausea/vomiting/abdominal pain [RD per 100, 0.32; 95% CI, 0.10-0.57]; non-Clostridioides difficile diarrhea [RD per 100, 0.46; 95% CI, 0.25-0.68]; vulvovaginal candidiasis/vaginitis [RD per 100, 0.36; 95% CI, 0.09-0.69]). Narrow-spectrum antibiotic regimens largely conferred similar risk of ADEs. We generally observed similar risks of each negative control outcome, indicating minimal confounding. Broad-spectrum antibiotics were associated with increased risk of ADEs among otherwise healthy adults treated for CAP in the outpatient setting. Antimicrobial stewardship is needed to promote judicious use of broad-spectrum antibiotics and ultimately decrease antibiotic-related ADEs.

Graph neural network-based subgraph analysis for predicting adverse drug events

PurposeAdverse drug events (ADEs) are a significant global public health concern, and they have resulted in high rates of hospital admissions, morbidity, and mortality. Prior to the use of machine learning and deep learning methods, ADEs may not become well recognized until long after a drug has been approved and is widely used, which poses a significant challenge for ensuring patient safety. Consequently, there is a need to develop computational approaches for earlier identification of ADEs not detected during pre-registration clinical trials. MethodsThis paper presents a state-of-the-art network-based approach that models patients as subgraphs composed of nodes of International Classification of Diseases (ICD) codes and directed edges illustrating disease progression. Four Graph Neural Network (GNN) variants were employed to make sub-graph level predictions that answer three Research Questions (RQ): 1) whether ADE(s) would occur given a patient's prior diagnoses history, 2) when an ADE would occur, and 3) which ADE would occur. The first and second RQs were addressed using a binary classification approach. The third RQ was addressed using a multi-label classification model. ResultsThe proposed network-based approach demonstrated superior performance in predicting ADEs, with the GraphSage model exhibiting the highest accuracy for both RQ 1 (0.8863) and RQ 3 (0.9367), while the Graph Attention Networks (GAT) model was found to perform best for RQ 2 (0.8769). Furthermore, an analysis segmented by ADE classification revealed that while RQs 1 and 3 exhibited minimal variance across different ADE categories, a distinct advantage was observed for categories B, C, and E in the context of RQ 2 when applying this sub-graph method. ConclusionThe network-based approach demonstrates the potential of GNNs in supporting the early detection and prevention of ADEs. Accurately predicting ADEs could enable healthcare professionals to make informed clinical decisions, take preventive measures and adjust medication regimens before serious adverse events occur. The proposed prediction method could also lead to optimized usage of healthcare resources by preventing hospital admissions and reducing the overall burden of adverse drug events on the healthcare systems.

Exploring Health Care Professionals' Perspectives on the Use of a Medication and Care Support System and Recommendations for Designing a Similar Tool for Family Caregivers: Interview Study Among Health Care Professionals.

With the aging population on the rise, the demand for effective health care solutions to address adverse drug events is becoming increasingly urgent. Telemedicine has emerged as a promising solution for strengthening health care delivery in home care settings and mitigating drug errors. Due to the indispensable role of family caregivers in daily patient care, integrating digital health tools has the potential to streamline medication management processes and enhance the overall quality of patient care. This study aims to explore health care professionals' perspectives on the use of a medication and care support system (MCSS) and collect recommendations for designing a similar tool for family caregivers. Fifteen interviews with health care professionals in a home care center were conducted. Thematic analysis was used, and 5 key themes highlighting the importance of using the MCSS tool to improve medication management in home care were identified. All participants emphasized the necessity of direct communication between health care professionals and family caregivers and stated that family caregivers need comprehensive information about medication administration, patient conditions, and symptoms. Furthermore, the health care professionals recommended features and functions customized for family caregivers. This study underscored the importance of clear communication between health care professionals and family caregivers and the provision of comprehensive instructions to promote safe medication practices. By equipping family caregivers with essential information via a tool similar to the MCSS, a proactive approach to preventing errors and improving outcomes is advocated.

PTB-DDI: An Accurate and Simple Framework for Drug–Drug Interaction Prediction Based on Pre-Trained Tokenizer and BiLSTM Model

The simultaneous use of two or more drugs in clinical treatment may raise the risk of a drug–drug interaction (DDI). DDI prediction is very important to avoid adverse drug events in combination therapy. Recently, deep learning methods have been applied successfully to DDI prediction and improved prediction performance. However, there are still some problems with the present models, such as low accuracy due to information loss during molecular representation or incomplete drug feature mining during the training process. Aiming at these problems, this study proposes an accurate and simple framework named PTB-DDI for drug–drug interaction prediction. The PTB-DDI framework consists of four key modules: (1) ChemBerta tokenizer for molecular representation, (2) Bidirectional Long Short-Term Memory (BiLSTM) to capture the bidirectional context-aware features of drugs, (3) Multilayer Perceptron (MLP) for mining the nonlinear relationship of drug features, and (4) interaction predictor to perform an affine transformation and final prediction. In addition, we investigate the effect of dual-mode on parameter-sharing and parameter-independent within the PTB-DDI framework. Furthermore, we conducted comprehensive experiments on the two real-world datasets (i.e., BIOSNAP and DrugBank) to evaluate PTB-DDI framework performance. The results show that our proposed framework has significant improvements over the baselines based on both datasets. Based on the BIOSNAP dataset, the AUC-ROC, PR-AUC, and F1 scores are 0.997, 0.995, and 0.984, respectively. These metrics are 0.896, 0.873, and 0.826 based on the DrugBank dataset. Then, we conduct the case studies on the three newly approved drugs by the Food and Drug Administration (FDA) in 2024 using the PTB-DDI framework in dual modes. The obtained results indicate that our proposed framework has advantages for predicting drug–drug interactions and that the dual modes of the framework complement each other. Furthermore, a free website is developed to enhance accessibility and user experience.

Comparative analysis of semaglutide induced adverse reactions: Insights from FAERS database and social media reviews with a focus on oral vs subcutaneous administration.

Compared to alternative weight-loss strategies and medications, semaglutide stands out for its convenience and efficacy, resulting in a significant increase in prescriptions and raising public safety concerns. Furthermore, the safety profiles of its oral and subcutaneous formulations require further examination. Our goal is to investigate the potential safety risks associated with semaglutide by analyzing data from the FAERS database and social media. Additionally, we aim to compare the adverse drug reaction (ADR) signals between the oral and subcutaneous administration routes of semaglutide. We collected semaglutide-related reports from the FAERS database spanning Q1 2018 to Q2 2023, and patient reviews on WebMD and AskaPatient up to 20 July 2023. Following data extraction and cleansing, we conducted descriptive analyses of demographic characteristics. Subsequently, we calculated adverse drug reaction (ADR) signals using the reporting odds ratio (ROR). We identified 19,289 and 422 semaglutide-related adverse drug events (ADEs) reported in the FAERS database and online patient reviews, respectively. Gastrointestinal disorders emerged as the most commonly reported System Organ Class (SOC) in both datasets. Predominant Preferred Terms (PTs) included nausea, vomiting, and diarrhea. Serious outcomes constituted 3.07% and 2.25% of all cases for oral and subcutaneous semaglutide, respectively. At the SOC level, gastrointestinal disorders accounted for 30.19% of total ADEs in oral semaglutide, slightly surpassing the 27.76% in subcutaneous semaglutide. The median onset for gastrointestinal PTs was 4 days in both oral (Q1: 1, Q3: 32) and subcutaneous (Q1: 1, Q3: 35) formulations. Noteworthy, new serious adverse event (AE) signals were identified, including hemorrhagic diarrhea (ROR: 3.69), hepatic pain (ROR: 4.20), abnormal hormone levels (ROR: 6.51), and pancreatic failure (ROR: 36.34) in subcutaneous semaglutide, and Dupuytren's contracture (ROR: 46.85) in oral semaglutide. Our study delineates the safety profile of semaglutide using data from the FAERS database and social media. And identified novel ADR signals specific to oral and subcutaneous forms of semaglutide.

Green rush and red warnings: Retrospective chart review of adverse events of interactions between cannabinoids and psychotropic drugs.

Our objective was to systematically assess the prevalence and clinical features of adverse events related to interactions between cannabinoids and psychotropic drugs through a retrospective chart review. 1586 adverse event reports were assessed. Cases included in the analysis showed a high probability of a causal relationships between cannabinoid-psychotropic drug interactions and adverse events. Data extracted included age, sex, psychotropic drug, cannabinoid products, other medications, and the clinical outcomes and mechanisms of these interactions. Cannabinoids were involved in 8% of adverse events associated with the concomitant use of psychotropic drugs and other preparations. We identified 20 reports in which side effects presented a causal relationship with the use of psychotropic drugs and cannabinoids. Preparations containing 18% or more tetrahydrocannabinol (THC), presented significant side effects with the following antidepressants: mianserine (restless legs syndrome, urogenital pain, ventricular tachycardia), mirtazapine (pancreatitis, hyperhidrosis, arthralgia), quetiapine (myocarditis, renal failure, bradycardia, sialorrhea), haloperidol (ventricular arrhythmia, prolonged QTc), aripiprazole (prolonged QTc), ventricular tachycardia) and cariprazine (stomach pain, hepatotoxicity), sertraline (ataxia, hyperactivity, coma, hallucinations, anxiety, agitation, tachycardia, panic attacks, disorientation, headache, dizziness, blurry vision, severe emesis, xerostomia, dry eyes), trazodone (disorientation, memory impairment, sedation), fluvoxamine (tachycardia, tachypnoea, dysarthria, auditory hallucinations). Two out of 20 reports (10%) analyzed in our study was related with the simultaneous use of cannabidiol (CBD) oil and sertraline. Concomitant use of those substances was associated with the adverse events in form of diarrhea, emesis, fever and severe fatigue. Clinicians need to closely monitor adverse events resulting from the combined use of cannabinoids and psychotropic medications. The accumulation of side effects and pharmacokinetic interactions (including CYP and p-glycoprotein inhibition) between these drugs can lead to clinically significant adverse outcomes.