Potential Adverse Drug Reactions Research Articles

Absorption, Distribution, Metabolism, and Excretion of FDA‐approved Antisense Oligonucleotide Drugs

Absorption, distribution, metabolism, and excretion (ADME) are key biological processes for determination of a drug’s pharmacokinetic parameters, which have direct impacts on therapeutic efficacy and adverse drug reactions (ADRs). Drug structures, formulations, and administration sites and routes cause different classes of drugs to have various ADME characteristics and consequent impacts upon efficacy and ADRs. For example, orally administered small molecule drugs are usually absorbed and distributed by uptake transporters, biotransformed by phase I/II drug‐metabolizing enzymes, and excreted by efflux transporters. However, newly developed large molecule biological drugs, including antisense oligonucleotide (ASO) drugs, have substantially different ADME parameters. ASO drugs are single‐stranded antisense nucleic acids with diverse modes of drug action that induce mRNA degradation, exon skipping, and ASO‐protein interactions. ASOs have a great potential to treat certain human diseases that have not been treatable with small molecule drugs. The ADME behaviors of ASO drugs contribute to their unique set of ADRs and toxicity. To better understand their ADME features, ten FDA‐approved ASO drugs were selected, including Fomivirsen, Pegaptanib, Nusinersen, Mipomersen, Inotersen, Defibrotide, Eteplirsen, Golodirsen, Viltolarsen, and Casimersen. A comprehensive meta‐analysis was conducted on their formulation, dosage, sites of administration, local and systematic distribution, metabolism, degradation, and excretion. Membrane permeabilization and nucleotide degradation by endonucleases and exonucleases are major contributors to ADME features of the ASO drugs and these differ from the roles of transporters and metabolizing enzymes of small molecule drugs. The summarized information provides the most updated knowledge of ADME characteristics of these ASO drugs, leading to a better understanding of their therapeutic efficacy and potential ADRs and toxicity. Numerous knowledge gaps, particularly on cellular uptake and subcellular trafficking and distributions are identified and future perspective and directions are discussed.

Clinical Impact of Implementing a Nurse-Led Adverse Drug Reaction Profile in Older Adults Prescribed Multiple Medicines in UK Primary Care: A Study Protocol for a Cluster-Randomised Controlled Trial.

(1) Aims: Adverse drug reactions (ADRs) particularly affect older people prescribed multiple medicines. The professional bodies of nursing, medicine and pharmacy have issued guidelines on identification and management of ADRs; however, ADRs continue to account for ~10% unplanned hospital admissions in the UK. Current methods of ADR identification and management could be improved by multidisciplinary collaboration involving nurses. The aim of this study is to examine the impact of implementing the nurse-led Adverse Drug Reaction (ADRe) Profile in UK primary care. (2) Design: A pragmatic cluster-randomised controlled trial (RCT) followed by qualitative interviews in a sequential mixed-methods study. (3) Methods: For the cluster RCT, 60 patients aged ≥65 prescribed ≥5 regular medicines for long-term conditions will be recruited, 10 in each of 6 general practices. The intervention arm (n = 30) will complete the ADRe Profile, whilst the control participants (n = 30) continue to receive usual, standard care. Primary outcomes will include clinical impact on patients, benefit and prescription changes. On completion of the RCT, participants will be invited to semi-structured qualitative interviews, to evaluate the impact of the ADRe Profile from stakeholders’ perspectives, and to describe the contextual factors relevant to ADRe implementation. (4) Results: The findings of this study will evaluate the effectiveness of the ADRe Profile in identifying and resolving potential ADRs in primary care. Trial registration: This study was registered in ClinicalTrials.gov, registration number NCT04663360, date of registration—29 November 2021 (date of initial registration: 26 November 2020), protocol version 2, dated 8 January 2021.

Medical Big Data Analysis Using Machine Learning Algorithms in the Field of Clinical Pharmacy

Industrial reforms utilizing artificial intelligence (AI) have been progressing remarkably around the world in recent years. In medical informatics, the application of medical big data analytics using AI is also being promoted, and it is expected to provide screening methods for predicting potential adverse drug reactions (ADRs) and discovering new effects. Previously, we developed a unique ADRs analysis system that incorporates Accord.NET, an open-source machine learning (ML) framework written in the programming language C#, and uses the Japanese Adverse Drug Event Report (JADER) database. By using this system to analyze ADRs and screening the cause and severity of ADRs, information can be obtained to evaluate efficacy as well as ADRs. Although both statistical methods and ML are commonly used for prediction, a characteristic difference between them is that the former emphasizes causal relationships and the latter emphasizes prediction results. Therefore, it is important to distinguish between cases where decisions must be made with an emphasis on causality and those where decisions must be made by focusing on unknown risks, and statistical methods and ML should be selected and used as appropriate. Against this backdrop, this paper describes a use case and suggests that the proper use of AI tools to analyze medical big data will help clinical pharmacists practice optimal drug management for each patient.

Combined Use of Calcium-channel Blockers With Ombitasvir/Paritaprevir/Ritonavir Exacerbates Peripheral Edema in Elderly Japanese Patients

The antiviral agent ritonavir is a substrate for cytochrome P450 3A4 (CYP3A4); therefore, concomitant use of CYP3A4-metabolising drugs might cause adverse reactions to this drug. We investigated the plasma level of calcium channel blockers (CCBs) as CYP3A4 substrates and peripheral edema as a potential adverse drug reaction possibly caused by the anti-hepatitis C virus (HCV) regimen of ombitasvir/paritaprevir/ritonavir (OPR) and CCBs. We enrolled Japanese patients prescribed OPR for HCV infection. Peripheral edema was graded according to the Common Terminology Criteria for Adverse Events ver. 4. Plasma samples were collected on days 0, 7, 14, 28, and 42 after antiviral treatment, at the trough level. Out of 52 patients, 64% experienced grade 1 or grade 2 peripheral edema, but not grade 3. Concomitant use of CCBs significantly increased the emergence of grade 2 edema (62%), compared with patients treated solely with OPR (48%). The use of OPR significantly increased the plasma concentration of amlodipine. Peripheral edema in patients treated with OPR and CCBs, although tolerable, should be closely monitored.

Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitor-Associated Cardiotoxicity: A Recent Five-Year Pharmacovigilance Study.

Background: Clinical trials frequently reported anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) associated with cardiac adverse drug events (AEs) but minimal postmarketing data. We aimed to research real-world cardiac disorders associated with ALK-TKIs based on the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Extract reports from the FAERS from the first quarter of 2016 to the second quarter of 2021 were obtained. Data mining of cardiac disorders associated with ALK-TKIs was carried out using disproportionality analysis to determine the clinical characteristics of AEs. Results: In total, 605 cases were screened out. These events were found to be more prevalent in patients ≥45 years (50.74%) and women (50.74%). The onset time of cardiac disorders was variable and concentrated within 2 months, with a median time of 33 days. The outcomes tended to be poor, with 20.93% fatality proportion. Cardiac arrhythmia was a common adverse event of ALK-TKIs, especially bradycardia. Crizotinib and lorlatinib showed positive signals in cardiac disorders, especially in heart failure, and brigatinib presented no signals. The study also found that myocarditis caused by ceritinib and cardiomyopathy caused by lorlatinib may be potential new adverse drug reactions. Conclusion: ALK-TKIs were reported more frequently in cardiotoxicity than other drugs and could often manifest earlier. We also found potential new AE signals in specific drugs and need more clinical studies to confirm. Our study helps fill the safety information of ALK-TKIs in the heart and provides directions for further research.

Genetic Therapy and Molecular Targeted Therapy in Oncology: Safety, Pharmacovigilance, and Perspectives for Research and Clinical Practice.

The impressive advances in the knowledge of biomarkers and molecular targets has enabled significant progress in drug therapy for crucial diseases such as cancer. Specific areas of pharmacology have contributed to these therapeutic outcomes—mainly targeted therapy, immunomodulatory therapy, and gene therapy. This review focuses on the pharmacological profiles of these therapeutic classes and intends, on the one hand, to provide a systematic definition and, on the other, to highlight some aspects related to pharmacovigilance, namely the monitoring of safety and the identification of potential toxicities and adverse drug reactions. Although clinicians often consider pharmacovigilance a non-priority area, it highlights the risk/benefit ratio, an essential factor, especially for these advanced therapies, which represent the most innovative and promising horizon in oncology.

Tolerability of memantine monotherapy versus adding memantine as combination therapy

IntroductionPrior studies have focused on the clinical efficacy of combination therapy, donepezil and memantine, for patient's diagnosed with Alzheimer's disease. As a result, it has become increasingly routine for providers to prescribe both medications for all-cause neurodegenerative disorders in variable stages of disease. However, the potential adverse drug reactions while described as mild can have serious sequelae in older adults who are already managing the side effects of polypharmacy. This study looks to explore the tolerability of switching cholinesterase inhibitors to memantine monotherapy versus adding memantine as combination therapy for all-cause neurodegenerative disorders. Materials & MethodsThe study is an IRB approved retrospective chart review that includes 175 patients diagnosed with neurocognitive disorders (ICD 10 F00-F03.91 and ICD10 G30-G31.84). Only side effects reported to and recorded by a neurocognitive subspecialist at Jefferson's Memory Disorder Center from 2016 to 2019 were included. Results & DiscussionThe odds of a patient reporting side effects on combination therapy in comparison with those patients on memantine monotherapy reporting side effects were significantly greater (OR = 4.33, CI 95% (1.62, 11.52), p = 0.003). In our patient sample, more than 80% of the patients reporting side effects qualified as polypharmacy or excessive polypharmacy (Table 2). As a result, variable polypharmacy (p = 0.047) was statistically significant in the in a binary logistic regression model for predicting outcomes for patients on combination therapy (Table 3). Therefore, as a patient progresses to moderate-severe stages of disease, we recommend switching CI monotherapy to memantine monotherapy as opposed to adding memantine as combination therapy for those patients on more than 10 other medications to increase tolerability. Given the limitations of a smaller sample size, variables such as severity of disease, renal and liver impairment as well as medication dosing were not significant predictors (Table 3) for those reporting side effects on combination therapy.

A Data-Driven Medical Decision Framework for Associating Adverse Drug Events with Drug-Drug Interaction Mechanisms.

Adverse drug events (ADEs) occur when multiple drugs interact within an individual, thus causing effects that were not initially predicted. Such toxic interactions lead to morbidity and mortality. Contemporary research surrounding ADEs has tended to focus on the detection of potential ADEs without great concern for elucidating the associations of drug-drug interaction (DDI) mechanisms that can predict potential adverse drug reactions (ADRs). Such associations are of great practical importance for everyday pharmacovigilance efforts. This study presents a data-driven framework for conducting knowledge-driven data analysis that combines a semantic inference system and enrichment analysis in order to identify potential ADE mechanisms. The framework was used to rank mechanisms according to their relevance for DDIs and also to categorize ADEs based on the number of DDI mechanism associations identified through enrichment analysis. Its validity is demonstrated through using both commercial and publicly available DDI resources. The results of this study solidly prove the framework's effectiveness and highlight potential for future research by way of incorporating additional and broader data to deepen and expand its capabilities.

Absorption, Distribution, Metabolism, and Excretion of US Food and Drug Administration-Approved Antisense Oligonucleotide Drugs.

Absorption, distribution, metabolism, and excretion (ADME) are the key biologic processes for determination of a drug's pharmacokinetic parameters, which have direct impacts on efficacy and adverse drug reactions (ADRs). The chemical structures, dosage forms, and sites and routes of administration are the principal determinants of ADME profiles and consequent impacts on their efficacy and ADRs. Newly developed large molecule biologic antisense oligonucleotide (ASO) drugs have completely unique ADME that is not fully defined. ASO-based drugs are single-stranded synthetic antisense nucleic acids with diverse modes of drug actions from induction of mRNA degradation, exon skipping and restoration, and interactions with proteins. ASO drugs have a great potential to treat certain human diseases that have remained untreatable with small molecule-based drugs. The ADME of ASO drugs contributes to their unique set of ADRs and toxicity. In this review, to better understand their ADME, the 10 US Food and Drug Administration (FDA)-approved ASO drugs were selected: fomivirsen, pegaptanib, mipomersen, nusinersen, inotersen, defibrotide, eteplirsen, golodirsen, viltolarsen, and casimersen. A meta-analysis was conducted on their formulation, dosage, sites of administration, local and systematic distribution, metabolism, degradation, and excretion. Membrane permeabilization through endocytosis and nucleolytic degradation by endonucleases and exonucleases are major ADME features of the ASO drugs that differ from small-molecule drugs. The information summarized here provides comprehensive ADME characteristics of FDA-approved ASO drugs, leading to a better understanding of their therapeutic efficacy and their potential ADRs and toxicity. Numerous knowledge gaps, particularly on cellular uptake and subcellular trafficking and distribution, are identified, and future perspectives and directions are discussed. SIGNIFICANCE STATEMENT: Through a systematic analysis of the existing information of absorption, distribution, metabolism, and excretion (ADME) parameters for 10 US Food and Drug Administration (FDA)-approved antisense oligonucleotide (ASO) drugs, this review provides an overall view of the unique ADME characteristics of ASO drugs, which are distinct from small chemical drug ADME. This knowledge is useful for discovery and development of new ASO drugs as well as clinical use of current FDA-approved ASO drugs.

Genetic Risk Factors for Adverse Drug Reactions

The use of medicines may in some cases be associated with the development of drug-induced diseases (DIDs) аnd other adverse drug reactions (ADRs), which leads to an increase in morbidity/mortality rates, and/or symptoms forcing a patient to seek medical attention or resulting in hospitalisation. ADRs may develop due to changes in a patient’s genotype, which entail an inadequate pharmacological response. The aim of the study was to analyse and summarise literature data on genetic risk factors that cause DIDs аnd other ADRs. It was shown that the polymorphism of genes encoding enzymes of drug metabolism (CYP, UGT, NAT, TPMT, EPHX, GST, etc.) or carriers (transporters) of drugs (P-gp, BCRP, MRP, OATP, OCT, etc.) can change the pharmacokinetics of drugs, affecting their activity. Polymorphism of RYR1, CACNA1S, MT-RNR1, VKORC1, and other genes encoding receptors targeted by drugs, and human leukocyte antigen (HLA) gene, may affect drug pharmacodynamics by modifying drug targets or changing the sensitivity of biological pathways to pharmacological effects of medicines. Changes in drug pharmacokinetics and pharmacodynamics may cause DIDs аnd other ADRs. The use of pharmacogenetic tests will allow a personalised approach to patients’ treatment and prevention or timely detection of potential ADRs during therapy. Before prescribing some medicines, clinicians should use recommendations on their dosing based on pharmacogenetic tests, which are posted on the official websites of Pharmacogenomics Research Network (PGRN), Pharmacogenomics Knowledgebase (PharmGKB), and Clinical Pharmacogenetics Implementation Consortium (CPIC). The results of ongoing clinical studies on the effect of gene polymorphism on drug safety will soon allow for higher personalisation of the choice of pharmacotherapy and prevention of many ADRs, including DIDs.

Strategies prescribers and pharmacists use to identify and mitigate adverse drug reactions in inpatient and outpatient care: a cognitive task analysis at a US Veterans Affairs Medical Center

ObjectiveTo develop a descriptive model of the cognitive processes used to identify and resolve adverse drug reactions (ADRs) from the perspective of healthcare providers in order to inform future informatics...

Development and Validation of 'Prediction of Adverse Drug Reactions in Older Inpatients (PADROI)' Risk Assessment Tool.

BackgroundAdverse drug reactions (ADR) detection and prediction methods in hospitalized older adults remain imprecise. The identification of the risk factors for ADRs in this group of patients is crucial to develop plausible prediction models.ObjectiveThis study aimed at developing and validating a “Prediction of ADR in Older Inpatients (PADROI)” risk assessment tool in hospitalized older adults.Methods and MaterialsWe had previously conducted a derivational study that aimed to determine the risk factors of ADRs in hospitalized older adults. We developed the PADROI model as a potential ADR risk assessment tool incorporating 8 predictors each given a score by rounding off the respective adjusted odds ratios (AORs) to the nearest whole number. Subsequently, we conducted another prospective cohort among adults aged 60 years and older admitted to Gynecology and Obstetrics, Medical, Oncology, Surgery, and Psychiatry wards at Mbarara Regional Referral Hospital (MRRH) from July 5 to September 17, 2021.ResultsA total of 124 participants, 70 females and 54 males aged 60–95 years, were included in this validation cohort; 62 of them experienced 90 ADRs. When applied to the derivational cohort, the area under receiver operating characteristic curve (AUROC) for the PADROI model was shown to be 0.896 (0.869–0.923; at 95% CI). In the validation study, AUROC of PADROI was 0.917 (0.864–0.971 at 95% CI; p < 0.001). Overall, PADROI correctly predicted 91.7% of those who experienced an ADR.ConclusionUsing the adjusted odds ratios from our derivational cohort, we developed an ADR prediction tool (PADROI) that achieved an excellent AUROC (0.917), high sensitivity (87.1%) and specificity (90.3%). The current model demonstrated a high potential for clinical applicability which can be strengthened if similar results are reproduced in larger and multi-centered studies.

A Study of Prescribing Pattern of Non-Steroidal Anti-Inflammatory Drugsin the Department of Orthopaedics, KIMS Hospital and Research Centre,Bangalore

Background Non-Steroidal Anti-Inflammatory Drugs NSAIDs are the most commonly used drugs for the management of pain and inflammation with good efficacy.Objective To determine the prescribing patterns of NSAIDs to report and document the potential drug-drug interactions and adverse drug reactions associated with its usage.Methodology The present study was a cross-sectional observational and prospective study conducted over 200 patients. The patient details included socio-demographics like age gender chief complaint diagnosis and information on the drugs prescribed which included brand andor generic name dose dosing frequency formulation route of administration and duration of treatment.Results Among the subjects 32 were prescribed paracetamol 9 were prescribed diclofenac and 1 were prescribed aspirin and aceclofenac each. 34.5 were prescribed the combination of aceclofenac paracetamol 62.5 were prescribed two NSAIDs. 117 prescriptions showed no interactions with NSAIDs whereas 62 were found to have interactions among aceclofenac bromelain commonly.Conclusion The common NSAID prescribed was preferential COX-2 inhibitor and a majority of prescriptions were not found with any interactions with NSAIDs. The prescribing pattern in our department was found to be rational.

The impact of treatment choices on potential drug-drug interactions in hypertensive patients.

The aim of this study was to analyse potential drug-drug interactions (pDDIs) and their potential adverse drug reactions (ADRs) among hypertensive patients. Moreover, we investigated the possibility of reducing pDDIs with different treatment choices. This was a cross-sectional study including all outpatients with hypertension and two or more medications, treated in a university hospital in Serbia. Lexicomp Interact (Lexi-Comp, Inc., Hudson, OH) was used for identification of pDDIs and potential ADRs. Treatment choices were explored according to patient characteristics, treatment guidelines and the interacting potential of drugs. Data were analysed using descriptive analysis and multiple logistic regression. A total of 350 patients were included in this study, with average age (77 [36-98] years and 6.1 [2.5]) medications. The majority of patients (86.0%) had at least one clinically significant pDDI, and the average was 3.78 (3.90) (range 1-25). Suggestions for treatment change aimed mainly at eliminating drug duplications, reducing the use of thiazide diuretics, sulfonylureas, alpha-lipoic acid and pentoxifylline and increasing the use of calcium-channel blockers, when appropriate. pDDIs would have decreased to 2.10 (2.52), P <.001, yet male gender, ≥6 medications, cardiovascular diseases, diabetes, benign prostatic hyperplasia, would be predictive of two or more pDDIs. The main potential adverse outcomes of pDDIs were hypotension, renal failure, hypoglycaemia, bradycardia and lactic acidosis. Careful choice of drugs can reduce but not eliminate pDDIs and their potential ADRs in hypertensive patients. Close monitoring for hypotension, renal failure, hypoglycaemia, bradycardia and lactic acidosis is necessary.

Drug Utilization Study of Diuretics in Children with Hydrocephalus

Hydrocephalus is a condition characterized by a dynamic imbalance between formation and absorption of cerebrospinal fluid that increases the size of intracranial space of the brain and, in some situations, an extension of the outer space of the brain with or without increased ventricular size. This study aimed to examine the use of diuretics and identify drug therapy problems in hospitalized children with hydrocephalus through the medical record. The study design is observational retrospective with time-limited sampling based on data in medical records at 2010-2013 periods, found 17 of 70 patients using diuretics therapy. There are three categories of diuretic which are used were mannitol (70.6%), acetazolamide (23.5%), and a combination of mannitol and acetazolamide (5.9%). Diuretics can be used for pre-op, post-op, and pre &amp; post-op on all types of hydrocephalus. Still, the specific use of diuretics may be caused by variations in comorbid diagnoses, clinical data, and laboratory data for each patient. Adverse drug reactions are potentially dominant in DTP analysis, and these are 7 of 17 patients. Monitoring of serum electrolytes such as sodium and potassium is needed because it decreases are potential adverse drug reactions of diuretics.

Chinese-Named Entity Recognition From Adverse Drug Event Records: Radical Embedding-Combined Dynamic Embedding-Based BERT in a Bidirectional Long Short-term Conditional Random Field (Bi-LSTM-CRF) Model.

BackgroundWith the increasing variety of drugs, the incidence of adverse drug events (ADEs) is increasing year by year. Massive numbers of ADEs are recorded in electronic medical records and adverse drug reaction (ADR) reports, which are important sources of potential ADR information. Meanwhile, it is essential to make latent ADR information automatically available for better postmarketing drug safety reevaluation and pharmacovigilance.ObjectiveThis study describes how to identify ADR-related information from Chinese ADE reports.MethodsOur study established an efficient automated tool, named BBC-Radical. BBC-Radical is a model that consists of 3 components: Bidirectional Encoder Representations from Transformers (BERT), bidirectional long short-term memory (bi-LSTM), and conditional random field (CRF). The model identifies ADR-related information from Chinese ADR reports. Token features and radical features of Chinese characters were used to represent the common meaning of a group of words. BERT and Bi-LSTM-CRF were novel models that combined these features to conduct named entity recognition (NER) tasks in the free-text section of 24,890 ADR reports from the Jiangsu Province Adverse Drug Reaction Monitoring Center from 2010 to 2016. Moreover, the man-machine comparison experiment on the ADE records from Drum Tower Hospital was designed to compare the NER performance between the BBC-Radical model and a manual method.ResultsThe NER model achieved relatively high performance, with a precision of 96.4%, recall of 96.0%, and F1 score of 96.2%. This indicates that the performance of the BBC-Radical model (precision 87.2%, recall 85.7%, and F1 score 86.4%) is much better than that of the manual method (precision 86.1%, recall 73.8%, and F1 score 79.5%) in the recognition task of each kind of entity.ConclusionsThe proposed model was competitive in extracting ADR-related information from ADE reports, and the results suggest that the application of our method to extract ADR-related information is of great significance in improving the quality of ADR reports and postmarketing drug safety evaluation.

PharmVIP: A Web-Based Tool for Pharmacogenomic Variant Analysis and Interpretation.

The increasing availability of next generation sequencing (NGS) for personal genomics could promote pharmacogenomics (PGx) discovery and application. However, current tools for analysis and interpretation of pharmacogenomic variants from NGS data are inadequate, as none offer comprehensive analytic functions in a simple, web-based platform. In addition, no tools exist to analyze human leukocyte antigen (HLA) genes for determining potential risks of immune-mediated adverse drug reaction (IM-ADR). We describe PharmVIP, a web-based PGx tool, for one-stop comprehensive analysis and interpretation of genome-wide variants obtained from NGS platforms. PharmVIP comprises three main interpretation modules covering analyses of pharmacogenes involved in pharmacokinetics, pharmacodynamics and IM-ADR. The Guideline module provides Clinical Pharmacogenetics Implementation Consortium (CPIC) drug guideline recommendations based on the translation of genotypic data in genes having guidelines. The HLA module reports HLA genotypes, potential adverse drug reactions, and the relevant drug guidelines. The Pharmacogenes module is employed for prioritizing variants according to variant effect on gene function. Detailed, customizable reports are provided as exportable files and as an interactive web version. PharmVIP is a new integrated NGS workflow for the PGx community to facilitate discovery and clinical application.

Abstract 10547: Communication of Potential Adverse Drug Reactions in Patients Undergoing Percutaneous Coronary Intervention

Background: Patients need information on all aspects of prescribed drug therapy to make informed decisions about their treatment for autonomy. Purpose: This study assessed whether patients received information about potential adverse drug reactions (ADRs) from prescribed drug therapy before or after discharge following percutaneous coronary intervention (PCI). Furthermore, we sought to estimate associations with socio-demographics and concerns related to prescribed drug therapy. Methods: CONCARD PCI is a prospective multicentre cohort study including 3424 patients undergoing PCI. The study was conducted between June 2017 and May 2020 at seven large referral PCI centres in two Scandinavian countries. Clinical data were collected from patients’ medical records. Socio-demographic characteristics were obtained by self-report during index hospitalization. Four questions from the Heart Continuity of Care Questionnaire were used to determine if information about potential ADRs was provided before or after discharge. The Specific-Concerns Scale of the Beliefs about Medicines Questionnaire was used to assess concerns related to prescribed drug therapy. Logistic regression estimated whether lack of information was associated with sociodemographic characteristics. Results: Most patients were men (78%), with a mean age of 66 years (SD11, range 20-96 years) and married or living with a partner (75%). Before discharge from hospital, 59% reported being informed of potential ADRs and 50% were informed what to do if ADRs occurred. After hospital discharge, 26% reported having reviewed potential ADRs with healthcare providers, and 24% had reviewed what to do if ADRs occurred. Those who were not informed had increased concerns about their prescribed drug therapy compared to those who were informed at both time points (p&lt;0.001). Women (51%) were less likely to receive information about potential ADRs than men (63%) (p&lt;0.001). However, there were no substantial associations with age, education, income, or marital status. Conclusion: Four in ten patients reported not receiving information on potential ADRs from prescribed drug therapy, and this applied especially for women. Efforts to improve communication on ADRs and gender equity should be a priority.

Oral Squamous Cell Carcinoma Mimicking Medication-Related Osteonecrosis of the Jaws (MRONJ): A Case Series

(1) Background: Medication-related osteonecrosis of the jaw (MRONJ) is a potential adverse drug reaction of antiresorptive and/or antiangiogenic treatment. MRONJ is mostly diagnosed by anamnestic data, clinical examination and radiological findings, with signs and symptoms often unspecific. On the other hand, oral squamous cell carcinoma (OSCC) is characteristic for its pleomorphic appearance (e.g., ulcer, mucous dehiscence, non-healing post-extractive socket). We report three cases where OSCC mimicked MRONJ lesions. (2) Patients: Three patients undergoing amino-bisphosphonate treatment for osteoporosis presented with areas of intraorally exposed jawbone and unspecific radiological signs compatible with MRONJ. Due to the clinical suspicious of malignant lesion, incisional biopsy for histological examination was also performed. (3) Results: Histological examination of the tissue specimen revealed the presence of OSCC. All patients underwent cancer treatment. (4) Conclusions: Several signs and symptoms of OSCC may simulate, in patients with a history of anti-resorptive, MRONJ; for these reasons, it is important to perform histologic analysis when clinicians are facing a suspicious malignant lesion.

Rapid discovery of potential ADR compounds from injection of total saponins from Panax notoginseng using data-independent acquisition untargeted metabolomics.

Injection of total saponins from Panax notoginseng (ISPN) is a modern preparation derived from traditional Chinese medicine (TCM) and is widely applied in the treatment of cardiovascular, cerebrovascular, ophthalmology, and endocrine system diseases. With the increase in the clinical application of ISPN, its adverse drug reactions (ADRs) and related safety issues have attracted much attention. In the present study, a data-independent acquisition (DIA) strategy was proposed to comprehensively characterize the saponins contained in ISPN based on the ultra-high-performance liquid chromatography/quadrupole-Orbitrap MS (UHPLC/Q-Orbitrap MS) platform. As many as 276 saponins were detected, and 250 compounds were identified or tentatively identified based on the retention times and MS/MS data. Furthermore, a metabolomic strategy was utilized to discover the discriminative saponins between normal and ADR batches. The results showed that six saponins, including ginsenoside Rh4, ginsenoside Rk3, ginsenoside Rg5, ginsenoside Rk1, ginsenoside Rg6, and 20(S)-ginsenoside Rh2, were significantly different between the two groups. According to cytotoxicity analysis and degranulation detection of RBL-2H3 cells, ginsenoside Rg5, ginsenoside Rk1, and 20(S)-ginsenoside Rh2 were considered the potential compounds responsible for clinical ADRs, ultimately. In addition, the quantitative analysis showed that the content of these three compounds in ISPN samples with ADRs was generally higher than that in samples without ADRs. This study demonstrated that it is advisable to screen out potential markers related to ADRs for developing the quality standard of ISPN by the integration of untargeted metabolomic analysis and cell biology study, and thus reduce its ADRs in the clinic.