Adverse Drug Reactions Research Articles

Narrow Therapeutic Index Drugs: FDA Experience, Views, and Operations.

The U.S. Food and Drug Administration (FDA) has defined narrow therapeutic index (NTI) drugs as "those drugs where small differences in dose or blood concentration may lead to serious therapeutic failures and/or adverse drug reactions that are life-threatening or result in persistent or significant disability or incapacity." FDA has undertaken efforts to develop NTI assessment criteria and enhance public confidence in generic NTI drugs through public workshops, research, and post-marketing surveillance. In 2015, FDA formed the NTI Drug Working Group to develop a consistent approach to identify NTI drugs and resolve NTI-related scientific and regulatory issues in a transparent and collaborative manner. One key objective of the NTI Drug Working Group is to evaluate potential NTI drugs based on five general characteristics of NTI drugs as highlighted in the case example for theophylline drug products. As of January 5, 2024, there are 33 drug products, with 14 distinct active ingredients, specified as NTI drugs in their respective product-specific guidances (PSGs) for generic drug development. Future collaborative efforts with other agencies to harmonize the terms and definitions for NTI drugs may help enhance clarity and consistency during the drug development and the regulatory review process.

Precision Medicine in Anesthesia: Pharmacogenomics and Personalized Care

Precision medicine in anesthesia represents a transformative approach aimed at optimizing anesthetic care by tailoring interventions to individual patient characteristics, particularly their genetic profile. Pharmacogenomics, a cornerstone of precision medicine, explores the genetic factors influencing drug metabolism, efficacy, and adverse reactions. This article delves into the integration of pharmacogenomics in anesthesia, discussing its impact on drug selection, dosage adjustments, and patient outcomes. It also highlights the potential for reducing perioperative complications, enhancing patient safety, and improving recovery through personalized anesthetic care. Challenges such as the need for robust genetic databases, ethical considerations, and the cost-effectiveness of implementing precision medicine in clinical practice are also discussed. The future of anesthesia lies in harnessing pharmacogenomics to provide individualized care, ultimately advancing patient-centric anesthetic management.

Off-Label Use of Monoclonal Antibodies for Eosinophilic Esophagitis in Humans: A Scoping Review

Background: Eosinophilic esophagitis (EoE) is a rare, chronic immune-mediated disorder with limited treatment options. Despite the U.S. Food and Drug Administration (FDA) approval of dupilumab for EoE, other monoclonal antibodies remain unapproved and are used off-label with limited evidence on their efficacy and safety. This systematic review rigorously and comprehensively evaluates the evidence for monoclonal antibody therapies used off-label to treat EoE. Methods: We conducted a systematic review across PubMed, EMBASE, Cochrane Central, and ClinicalTrials.gov, assessing the efficacy and safety of off-label monoclonal antibodies in EoE through clinical outcomes and the FDA Adverse Event Reporting System (FAERS) data. Results: Among ten monoclonal antibodies reviewed, mepolizumab that targets IL-5 showed the most promise with a moderate recommendation based on Level 2 evidence. Others like omalizumab (anti-IgE), dectrekumab (anti-IL-13), and reslizumab (anti-IL-5) showed limited utility. Safety evaluations via the FAERS database revealed significant adverse drug reactions, including serious events like asthmatic crises, pneumonia, and adrenal insufficiency for mepolizumab and reslizumab, as well as chronic obstructive pulmonary disease and gastroenteritis for omalizumab. Dectrekumab’s safety profile remains unclear due to a lack of data. Conclusions: While mepolizumab demonstrates potential as an off-label treatment, none of the antibodies reviewed have FDA approval for EoE. Clinicians should consider the balance between local and systemic effects and exercise caution, closely monitoring for adverse effects, particularly in patients with respiratory comorbidities. Continued research is crucial to establish a more robust evidence base for these therapies.

Dealing with adverse drug reactions in the context of polypharmacy using regression models

Polypharmacy in older adults increases the risk of adverse drug reactions (ADRs), but studying this relationship is complex. In real-world data, the high number of medications, coupled with rare drug combinations, results in high-dimensional datasets that are difficult to analyze using conventional statistical methods. This study applies horseshoe and lasso regression for analyzing rare events in polypharmacy contexts, focusing on severe ADRs such as falls and bleedings. These regression models are executed on a multi-center dataset compiling 7175 cases from the ADRED project to detect potential ADR-associated drugs among 100 most common drugs in emergency department admissions. Positive predictors are classified by using 50% and 90% credibility intervals. This study demonstrates that regression models with horseshoe or lasso priors are effective for analyzing ADRs, providing a comprehensive consideration of multiple factors in large, sparse datasets and improving signal detection in polypharmacy, addressing a significant challenge in pharmacovigilance. Both priors yielded consistent and clinically meaningful results. The horseshoe regression resulted in fewer potential positive predictors overall, which could make it suitable as a diagnostic tool. While these regressions generate valuable information, there are still challenges in setting appropriate thresholds for determining and interpreting the positive results.

Signals of Possibly Persistent Gustatory, Olfactory and Auditory Adverse Drug Reactions to Antibiotic Drugs: A Disproportionality Analysis Using the EudraVigilance Database.

In 2018, the European Medicines Agency issued some risk minimisation measures related to unresolved adverse drug reactions (ADRs) reported for fluoroquinolones, including sensory ADRs. Spontaneous reporting databases frequently report unresolved outcomes for gustatory, olfactory and auditory (GOA) ADRs. However, such a high volume of unresolved GOA ADRs could reflect an under-investigated clinical issue or an intrinsic difficulty in the outcome assessment. The objectives of the study were: (1) to investigate whether unresolved outcomes are reported more frequently for GOA ADRs than for other ADRs to systemic antibiotics and (2) to identify possible signals of unresolved GOA ADRs for systemic antibiotics. We used the EudraVigilance database to extract the number of ADRs to systemic antibiotics of the Anatomical Therapeutic Chemical class J01 up to February 2019. We classified ADRs in "non-GOA ADRs" and "GOA ADRs". Adverse drug reactions were categorised in three groups according to the outcome: defined, persistent/permanent (unresolved) and undetermined ADRs. We performed disproportionality analyses with the case/non-case methodology, by calculating the crude reporting odds ratio (ROR) and 95% confidence interval (CI). Cases were all persistent/permanent ADRs, and non-cases were defined and undetermined ADRs. For the first objective, index groups were gustatory or olfactory or auditory ADRs, while reference group included all non-GOA ADRs. For the second objective, we performed a disproportionality analysis by using the sub-set of GOA ADRs. Index and reference groups varied with subgroups of drugs and drug class, so that each drug and drug class was compared with the others. We conducted two sensitivity analyses for each analysis by varying the case definition. We extracted 748,798 ADRs, including 10,770 GOA ADRs. The first analysis showed that GOA ADRs were reported more frequently as unresolved events compared with all other ADRs (ROR: 2.68 95% CI 2.51-2.85; ROR: 5.20 95% CI 4.66-5.81; and ROR: 2.64 (95% CI 2.51-2.79, respectively). Gustatory ADRs were reported more frequently as unresolved for doxycycline (ROR: 1.69, 95% CI 1.18-2.41, p = 0.0038), azithromycin (ROR: 2.07, 95% CI 1.58-2.72, p < 0.0001) and levofloxacin (ROR: 1.59, 95% CI 1.22-2.07, p < 0.001) compared with GOA ADRs of all other antibiotics. Olfactory ADRs were reported more frequently as unresolved for doxycycline (ROR: 2.4, 95% CI 1.26-4.58, p = 0.0078) and levofloxacin (ROR: 1.92, 95% CI 1.28-2.86, p = 0.0014). Auditory ADRs were reported more frequently as unresolved for doxycycline (ROR: 1.52, 95% CI 1.09-2.12, p = 0.013) and clarithromycin (ROR: 1.31, 95% CI 1.09-1.59, p = 0.0049). We tested and used an appropriate expected frequency standard, which allows us to identify possible signals of unresolved GOA ADRs to antibiotic drugs in the EudraVigilance database. This approach could be used to generate signals of persistent or even irreversible events for other drugs or adverse reactions. However, these signals must be confirmed with a thorough clinical assessment.

Exploring patients’ views and experiences of side-effects and how they are reported, a focus group study

Abstract Introduction Adverse drug reactions (ADRs) are an increasing health concern, causing considerable physical, psychological and economic impacts1,2. The yellow card scheme (YCS) is the UK’s spontaneous reporting system, allowing patients and healthcare professionals to report ADRs (3). Research has shown that patient reports could provide a beneficial insight into real-world situations and are a key aspect of pharmacovigilance2. Despite this, under-reporting by patients remains a significant issue that needs to be addressed1. Aim This study aimed to explore views and experiences of the public regarding ADR reporting. Methods Following approval from Cardiff University School of Pharmacy and Pharmaceutical Sciences Research Ethics Committee, adult members of the South Wales public who had experienced an ADR (“side-effect”) were invited via social media outlets such as Facebook and WhatsApp to participate in an online (Zoom) focus group to discuss their ADR experience (including whether they reported) and knowledge and views on the YCS. Healthcare professionals were excluded from the study. Written informed consent and demographic information via a short online survey were obtained prior to the focus group. The focus groups were audio and video recorded via Zoom and discussions were transcribed verbatim. A thematic analysis was executed to identify fundamental themes. Results Four focus groups, involving 11 participants took place. The sample consisted mostly of females between 18-30 years of age from an ethnic minority background. Themes identified were lack of knowledge of ADRs and the YCS; support and barriers to reporting ADRs and strategies for improving YCS reporting. There was a lack of knowledge of ADRs with uncertainty over the concept of “side-effect” and varying degrees of understanding on the topic. All participants had suffered side-effects that were severe in nature, affecting them physically, psychologically or cosmetically. None of the participants had any concept of the YCS and side-effect reporting. Despite this, participants felt reporting of side-effects was vital to ensure the safety of medications and prevention of patient harm. The majority of participants sought support for side-effects from a General Practitioner (GP) or community pharmacist, although difficulties accessing GP appointments was a barrier. Strategies suggested for increasing awareness of YCS to increase ADR reporting were use of posters, social media, QR codes, online prompts, coffee mornings and letters sent home to parents from schools. Discussion / Conclusion If patients are unsure around the concept of a side-effect and don’t know about the YCS, reporting rates will continue to fall. Although it is recognised that the sample is not fully representative of the Welsh population, this small-scale exploratory study has nevertheless identified some possible concerns but also some opportunities to engage patients in ADR reporting. Patient education by healthcare professionals on side-effects, alongside increased promotion of the YCS via social media and advertisements in healthcare settings are key opportunities to increase patients’ awareness and understanding of ADRs and ADR reporting. Further research is essential to understand the extent of these issues and also to investigate how healthcare professionals can facilitate this process. Follow-up studies are planned.

Impact of multifaceted interventions on the knowledge, attitude, and practice of adverse drug reactions reporting among healthcare workers in Vietnam: a comparative intervention study

BackgroundKnowledge, attitude, and practice of Adverse Drug Reactions (ADRs) and ADRs reporting among healthcare workers were related to the quality and ADRs reporting rate. The aim of this study was to evaluate the effectiveness of the multifaceted interventions on knowledge, attitude, and practice (KAP) of healthcare workers and to compare the proportion of spontaneous ADRs reports at the study center, before and after instituting multifaceted interventions.MethodsA comparative intervention study was conducted among healthcare workers at the hospital. The participants were asked to complete a questionnaire before and after instituting the multifaceted interventions to assess the KAP of ADRs and their reporting. The impact of the multifaceted interventions was assessed by comparing their correct responses to the KAP questions and the proportion of spontaneous ADRs reports before and after the interventions. The pre- and post-intervention scores for KAP questions were compared usingMcNemar test by R Language.Results388 healthcare workers completed the study. The proportion of participants qualified for ADRs reporting increased significantly, from 73.5% (pre–intervention) to 99.2% (post–intervention) for knowledge scores, from 70.6% to 91.8% for attitude scores, and from 81.4% to 97.2% for practice scores (p &amp;lt; 0.001). Similarly, the number of spontaneous ADRs reports increased by 31% after 3 months of interventions.ConclusionMultifaceted interventions instituted at the study center improved the knowledge, attitude, and practice of health workers towards ADRs and spontaneous reporting. It would be beneficial to implement such interventions in other hospitals in Vietnam.

Belimumab safety in adult and paediatric Chinese patients with systemic lupus erythematosus: A Phase 4, multicentre, observational study.

Although belimumab has been widely used in patients with systemic lupus erythematosus (SLE) globally, real-world safety data among Chinese patients are limited, particularly for children. This study assessed the safety and tolerability of belimumab in adult and paediatric patients with SLE in China in real-world clinical practice. This Phase 4, multicentre, prospective, observational study enrolled patients prescribed intravenous belimumab by their physicians in tertiary hospitals, independent of a clinical study, during routine clinical visits between May 2021 and May 2022. Patients could have been receiving belimumab prior to enrolment. The primary objective was to describe the incidence of adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs) and AEs of special interest (AESIs) over the 24-week follow-up period. Data were collected at enrolment and approximately 4, 12 and 24weeks post-enrolment, during routine clinical visits. AEs, ADRs and SAEs were collected as independent events. The safety population comprised patients who received ≥1 dose of belimumab and completed ≥1 follow-up visit. Overall, 417 patients were included in the analysis (safety population); 89.2% were female and mean (standard deviation) age was 35.5 (11.9) years. AEs were reported in 158 patients (37.9%) and were mostly mild (79.1%). The most common AEs were upper respiratory tract infections (n = 19, 4.6%) and hypokalaemia (n = 18, 4.3%; all mild). Among 22 patients (5.3%) with SAEs, four patients (1.0%) had drug-related SAEs (pneumonia, respiratory tract infection, gingivitis and decreased white blood cell and neutrophil count). ADRs were experienced by 25 patients (6.0%), most commonly urinary tract infections (n = 5, 1.2%). There were no fatal SAEs. AESIs occurred in 14 patients (3.4%), including infections of interest (n = 5, 1.2% all herpes zoster), serious selected psychiatric events (n = 3, 0.7%) and infusion-related systemic and anaphylactic reactions (n = 7, 1.7%). Of 14 paediatric patients enrolled, six experienced AEs, zero ADRs, two SAEs and one AESI. Belimumab was generally well tolerated in adult and paediatric patients with SLE in this real-world setting in China, with no new safety signals identified. Future assessment of long-term belimumab safety in China beyond 24weeks will extend this current body of evidence.

Pharmacogenetic testing: current state of the issue

Aim. The purpose of this work is to emphasize the importance and practical benefits of pharmacogenetics in medicine, demonstrating how the integration of pharmacogenetics into clinical practice can improve treatment outcomes and enhance the safety of therapies. Pharmacogenetics is a rapidly developing branch of pharmacology that studies how genetic variation affects an individual’s response to drugs. By understanding these genetic differences, healthcare providers can tailor drug therapy to maximize efficacy and minimize adverse drug reactions. The field aims to move away from the traditional one-size-fits-all approach and instead personalize medical treatment based on a person’s genetic makeup. The ability to predict a person’s response to medication based on their genetic profile has profound implications. For example, pharmacogenetic testing can identify patients at risk for life-threatening adverse drug reactions, such as drug-induced liver injury. This proactive approach can prevent adverse events, improving patient safety and the overall quality of care. In addition, pharmacogenetics aids in the development of new drugs by identifying genetic markers associated with drug responses, optimizing the drug development process, and reducing the time and costs associated with bringing new drugs to market. Key advances in pharmacogenetics include the identification of genetic polymorphisms in enzymes, such as cytochrome P450, that affect drug metabolism, thereby influencing both safety and efficacy. Pharmacogenetic testing allows doctors to predict the best drug and dosage for a patient, improving treatment outcomes and reducing the risk of adverse drug events. Despite its potential, the integration of pharmacogenetics into clinical practice faces challenges, including a lack of reliable clinical evidence, inadequate physician education, and the need for a comprehensive health IT infrastructure to support the use of genetic data. Ethical and legal issues, such as patient privacy and the risk of genetic discrimination, also present significant obstacles. However, continued research, the development of genetic testing technologies, and interdisciplinary collaborations are paving the way for more widespread adoption of pharmacogenetics, which promises to significantly improve patient care and healthcare efficiency. Key resources such as PharmGKB, CPIC, and the NIH provide valuable information and guidance for clinicians, researchers, and students, helping bridge the gap between genetics research and clinical application. Conclusions. Pharmacogenetics represents a significant advancement in personalized medicine, offering the potential to tailor drug therapies to individual genetic profiles. Although the field has made substantial progress, challenges remain in the form of insufficient clinical evidence, implementation barriers, and ethical concerns. Continued research and collaboration among stakeholders are essential to fully realize the benefits of pharmacogenetic testing in clinical practice.

Tapentadol: navigating the complexities of abuse, patient safety & regulatory measures

Aim To evaluate tapentadol abuse cases by analyzing real-world data and identifying under-reporting countries from Southeast Asian Region (SEAR) to enhance vigilance. Method A retrospective, observational study from 2013 to March 2024 using VigiBase was conducted. Result Tapentadol-related abuse falls within the System Organ Class (SOC) categories of psychiatric disorder, nervous system disorder and injury, poisoning, and procedural complications. These are further categorized into Preferred Terms (PT) such as anxiety, delirium, Central Nervous System toxicity, depressive disorder, drug abuse, dependence/withdrawal syndrome, and overdose using the Medical Dictionary for Regulatory Activities (MedDRA) system. Among the 11 countries in the SEAR, India is the only country to report cases of tapentadol-related abuse, no Individual Case Safety Reports (ICSRs) related to tapentadol abuse have been submitted from other SEAR nations. Out of 127 ICSRs concerning tapentadol-related adverse events reported in India, 20 cases involved abuse. Focusing on the ICSRs submitted in India, the reported adverse reactions included anger(n = 1,10%), anxiety (n = 2, 10%), delirium (n = 1, 5%), drug abuse (n = 4, 20%), drug dependence/withdrawal syndrome (n = 7, 35%), intentional overdose (n = 2, 10%), depressive disorder (n = 1, 5%), euphoric mood (n = 1, 5%), and product misuse (n = 1, 5%) indicating a concerning pattern of substance abuse. Conclusion Stringent regulatory actions are needed to curb this practice in India, such as rescheduling tapentadol from Schedule H (Prescription drugs) to Schedule X(Narcotic drugs) in India could offer more regulatory oversight and measures to reduce risks related to abuse, addiction, and dependence while enhancing patient safety in pain management practices. Additionally, tapentadol should be closely monitored in other SEAR countries due to its potential for dependence. This study also emphasizes the importance of encouraging SEAR countries to report more Adverse Drug Reactions (ADRs), which would facilitate the implementation of more rigorous regulatory measures.

EVALUATION OF KNOWLEDGE, ATTITUDE, AND PRACTICE ABOUT PHARMACOVIGILANCE AMONG NURSING STAFF AT TERTIARY CARE TEACHING HOSPITAL

Objectives: The primary objective of this study was to evaluate the knowledge, attitude, and practice of nursing staff about pharmacovigilance and adverse drug reactions (ADRs) reporting in a tertiary care teaching hospital. The secondary objective was to assess the causes of underreporting of ADRs. Methods: A cross-sectional questionnaire-based study was carried out using a pre-designed structured questionnaire, adapted from previous studies and validated internally among the members of the pharmacovigilance committee. This questionnaire was provided to the nurses of all wards and out-patient department in a tertiary care teaching hospital of Gujarat, after taking their written informed consent. The data were evaluated for further analysis. Results: Out of 309 participants, 73.38% had appropriate knowledge about pharmacovigilance and ADRs and 72.41% had a positive attitude toward the safety of drugs and reporting of ADRs. Out of 309 nurses, 55.34% of nurses came across an ADR and 3.56% of nurses had reported an ADR. According to the evaluated data, the reasons for underreporting of ADRs were lack of awareness, lack of time, and fear of legal implications. Out of all participants, 4.85% had attended ADR training/awareness sessions. Conclusion: In the present study, nursing staff at a tertiary care teaching hospital had good knowledge and positive attitude toward pharmacovigilance but at the same time application of the same was lacking. Exposure to awareness programs and seminars about pharmacovigilance and hands-on ADR training sessions can improve the practice of nurses about pharmacovigilance.

Diffuse lung diseases ascribed to drugs: a nationwide observational study over 37 years using the French pharmacovigilance database.

Drug-induced interstitial lung disease (DI-ILD) is a heterogeneous subgroup of interstitial lung diseases (ILD). The number of molecules involved is increasing with time. Due to their low incidence, DI-ILDs may be detected only after a drug has been marketed, notably through Adverse Drug Reaction (ADR) reports to pharmacovigilance centres. The aim of our study was to describe drug-induced diffuse lung disease cases notified to and recorded by the French Pharmacovigilance Database (FPVD), reported clinical pictures and the potentially causal drugs. This retrospective study included cases registered in the FPVD from 1st January 1985 to 1st April 2022 which had ADR coded in MedDRA with a High Level Group Term "Lower respiratory tract disorders (excluding obstruction and infection)" involving patients aged 18 and over. We analysed 7234 cases involving 13 059 suspect medications and 1112 specific molecules. Cases were categorised as serious in 96.7% and in 13.3% death ensued. Men accounted for 54.4% of the cases. Median age was 69 [18-103] years. The most prevalent ADRs were "ILD" (51.0%), "Pulmonary oedema" (acute/non-acute) (15.6%) and "Pulmonary fibrosis" (10.5%). "Anti-cancer drugs" (31.2%) and "Cardiovascular drugs" (29.1%) were the most prominent therapeutic classes involved, with amiodarone being the most commonly reported suspected drug (10.0%), followed by methotrexate (3.1%). This study from a large nationwide dataset spanning 37 years is the largest known to date. Drug-induced diffuse lung diseases are serious with a potentially fatal outcome. Accurate diagnoses remain essential to identify it properly and discontinue the culprit drug urgently.

EVALUATION OF CUTANEOUS ADVERSE DRUG REACTIONS IN A TERTIARY CARE HOSPITAL IN SOUTHERN INDIA: A RETROSPECTIVE ANALYSIS

Objective: This study was undertaken to understand the demographic profile, common causative drugs, and the presentations of cutaneous adverse drug reactions (CADR) among the patients of our hospital. Methods: This is a retrospective analytical study. All CADR reported to our adverse drug reaction monitoring center from dermatology outpatient department (OPD), other OPDs, intensive care units, and inpatient wards of our hospital from September 2022 to March 2024 was collected from VIGIFLOW (software used by the pharmacovigilance program of India). The data was then analyzed. Results: A total of 272 CADR were reported over the study period. The median age of presentation was 41 years (Interquartile range=23). Overall 44 (16.18%) serious and 228 (83.82%) non-serious CADR were reported. Erythematous maculopapular rash was the most common clinical presentation (63%). Bullous exfoliative drug eruptions and Stevens Johnson’s syndrome were some of the serious CADR. The most common suspected medications were antibiotics (42.15%) followed by non-steroidal anti-inflammatory drugs (8.92%). In 76% of the cases, the suspected medication was withdrawn. The outcome was reported as “Recovering” in 52% of the cases. On causality assessment, 251 (92%) CADR were classified as “Possible.” Conclusion: A CADR is a common yet preventable health problem. As seen from our study, most of the suspected medications were withdrawn and subsequently the patients were recovering from the CADR. Hence, early diagnosis, identification, and withdrawal of the implicating drugs help in timely recovery and prevention of complications, which in turn help in decreasing the burden on our healthcare system.

A real-world study of adverse drug reactions of two isocitrate dehydrogenase inhibitor based on the US FDA adverse event reporting system and VigiAccess databases

A real-world study of adverse drug reactions of two isocitrate dehydrogenase inhibitor based on the US FDA adverse event reporting system and VigiAccess databases

Pharmacogenetics of colorectal cancer in a third-level hospital in Valencia

Abstract Objectives Genetic variants with associated pharmacokinetic and pharmacodynamic effects have an impact on the development of adverse drug reactions and survival of patients with colorectal cancer. Methods A selection of genetic variants was performed according to the established chemotherapy and the pharmacogenetic databases. Genotyping was performed using MassArray technology (Agena Bioscience). Variant-toxicity and survival-genotype correlations were assessed using logistic regression (SPSS v.28.0.1.1). Results Genotyping of 25 SNPs was performed in 96 patients. In relation to the DPYD gene, 3.5 % had the rs75017182 mutation; 4.7 % the rs1801158 mutation and 7.1 % the rs1801160 mutation. Genotypic frequencies in the UGT1A1 gene were 39.4 % (*1/*1); 37.9 % (*1/*28); 19.7 % (*28/*28); and 3 % (*1/*36). The genotypes CT of the rs1801160 variant, AT of the rs67376798 variant (DPYD) and *1/*36 (UGT1A1) were associated with low survival (p-value: 0.006, &lt;0.001, and 0.052, respectively). The most frequent adverse reactions were gastrointestinal disorders, followed by neurotoxicity. The CC genotype (rs1801160, DPYD) was associated with a lower risk for developing severe gastrointestinal events, whereas CC (rs1801158, DPYD) was associated with a lower risk of developing severe general hematologic toxicity. Conclusions The population frequencies obtained in our study for rs1801160 and rs75017182 (DPYD); and for *1/*28, *28/*, and *1/*36 (UGT1A1) were inconsistent with the frequencies reported for the Spanish population in the literature. The genotypes CT of rs1801160, AT of rs67376798 (DPYD), and 1/*36 (UGT1A1) were associated with lower survival rates.

Drug risks associated with sarcopenia: a real-world and GWAS study

IntroductionDrug-induced sarcopenia has not received adequate attention. Meanwhile, there is growing recognition of the importance of effective pharmacovigilance in evaluating the benefits and risks of medications.AimsThe primary aim of this study is to investigate the potential association between drug use and sarcopenia through an analysis of adverse event reports from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and to evaluate the genetic factors contributing to drug-induced sarcopenia using summary-data-based Mendelian randomization (SMR).MethodsWe obtained reports of adverse drug reactions from FAERS. Primary outcomes included sarcopenia and potential sarcopenia. We calculated the Proportional reporting ratio (PRR) to assess the risk of specific adverse events associated with various drugs, applying chi-square tests for statistical significance. Additionally, we used SMR based on Genome-wide association study (GWAS) to evaluate the potential associations between drug target genes of some significant medications and sarcopenia outcomes. The outcome data for sarcopenia included metrics as hand grip strength and appendicular lean mass (ALM).ResultsA total of 55 drugs were identified as inducing potential sarcopenia, and 3 drugs were identified as inducing sarcopenia. The top 5 drugs causing a potential risk of sarcopenia were levofloxacin (PRR = 9.96, χ2 = 1057), pregabalin (PRR = 7.20, χ2 = 1023), atorvastatin (PRR = 4.68, χ2 = 903), duloxetine (PRR = 4.76, χ2 = 527) and venlafaxine (PRR = 5.56, χ2 = 504), and the 3 drugs that had been proved to induced sarcopenia included metformin (PRR = 7.41, χ2 = 58), aspirin (PRR = 5.93, χ2 = 35), and acetaminophen (PRR = 4.73, χ2 = 25). We identified electron-transfer flavoprotein dehydrogenase (ETFDH) and protein Kinase AMP-Activated Non-Catalytic Subunit Beta 1 (PRKAB1) as the primary drug target genes for metformin, while Prostaglandin-endoperoxide Synthase 1 (PTGS1) and Prostaglandin-endoperoxide Synthase 2 (PTGS2) were considered the primary action target genes for aspirin and acetaminophen according to DrugBank database. SMR showed that the expression abundance of ETFDH was negatively correlated with right hand grip strength (blood: OR = 1.01, p-value = 1.27e-02; muscle: OR = 1.01, p-value = 1.42e-02) and negatively correlated with appendicular lean mass (blood: OR = 1.03, p-value = 7.73e-08; muscle: OR = 1.03, p-value = 1.67e-07).ConclusionsWe find that metformin, aspirin, and acetaminophen are specifically noted for their potential to induce sarcopenia based on the analyses conducted. We perform signal mining for drug-associated sarcopenia events based on real-world data and provides certain guidance for the safe use of medications to prevent sarcopenia.

Adverse Drug Reactions and Safety Profiles in Cardiovascular Drug Therapy: A Pharmacovigilance Analysis

Aims: The purpose of the study is to identify adverse drug reactions (ADRs) and evaluate patient knowledge of the disease using the Knowledge Assessment Questionnaire (KAQ). This study was designed to compare adverse effects on Cardiovascular Drug Therapy. Adverse drug reaction (ADRs) is a major cause of mortality worldwide. The objective of the present study were a) to find out the prevalence of adverse drug reaction (ADRs) in the hospitalized patient by active surveillance, b) to study the profile of ADRs detected. (3) This study was done in superspecialty hospital Netaji Subhash Chandra Bose medical college &amp; Hospital, Jabalpur, for three month study. Methodology: This study was Pharmacovigilance group, belonging to department of cardiology at Netajisubhash Chandra bose medical college, Jabalpur M.P. (5) Total number of patients taken for study was 90 in number. Results and Conclusion: Total 90 subjects were recruited in the study. Drug used for their co morbidities to find out ADRs in which maximum ADRs found in chronic rheumatoid heart diseases, for this diseases patient took in two combination mainly Digoxin with Clopidogrel (47.36%) and another were with atorvastatin, spironolactone and warfarin (47.30% ADRs Adverse drug reactions on particular body system were mostly observed on CNS (32.14% ADRs). According to Naranjonaranjo causality assessment scale applied to this study illustrates that the maximum possible and probable adverse drug reaction were shown on Furosemide as well as for Digoxin and Spironolactone.

Cardiac involvement in dermatological disorders: A narrative review

Recent studies have highlighted several pathogenic connections between skin disorders and cardiac manifestations. Dermatologists frequently encounter several genetic or inherited skin conditions that can have significant cardiac implications, including septal defects, cardiomyopathy, and valvular heart disease, which may sometimes be life-threatening. In this review, primary cutaneous disorders having cardiac manifestations are described. A comprehensive narrative review of the literature was conducted by searching articles published through November 2023 in the PubMed and Google Scholar databases. Original research articles, review articles, case reports, case series and other relevant English-language publications were included. The review identified several congenital diseases, inflammatory conditions, connective tissue disorders, and adverse drug reactions that have both skin and cardiac involvement. Diagnosing these cardiac manifestations in patients with skin conditions is crucial for appropriate management, timely intervention and effective patient counselling.

Electroconvulsive Therapy in a Left Ventricular Assist Device Recipient With Treatment-Resistant Depression.

Depression and heart failure are highly comorbid, with up to 35% of heart failure patients suffering from comorbid depression. Left ventricular assist devices (LVADs) serve as a major lifeline for patients with heart failure; however, despite the drastic improvement in cardiac function following LVAD implantation, up to 24% of LVAD recipients suffer from depression. Depression management in LVAD recipients is often complicated by the recipient's increased risk for antidepressant side effects, adverse drug reactions, and inability to safely receive certain interventional psychiatry therapies, as the LVAD is either a relative or absolute contraindication. Electroconvulsive therapy (ECT) is highly effective for treatment-resistant depression; although it carries increased cardiovascular risks for the LVAD population (particularly bradycardia/hypotension and tachycardia/hypotension), these can be continuously monitored, along with LVAD function, such that with the close cooperation of a multidisciplinary team, the risks of ECT can be minimized. To our knowledge, there is only one published case report of ECT in an LVAD recipient. We present a case of an LVAD recipient with treatment-resistant depression who was successfully treated with ECT. Our case describes an approach by which ECT can be safely delivered to LVAD recipients with a collaborative multidisciplinary team approach.

Genomic variations associated with risk and protection against vincristine-induced peripheral neuropathy in pediatric cancer patients

Vincristine-induced peripheral neuropathy is a common and highly debilitating toxicity from vincristine treatment that affects quality of life and often requires dose reduction, potentially affecting survival. Although previous studies demonstrated genetic factors are associated with vincristine neuropathy risk, the clinical relevance of most identified variants is limited by small sample sizes and unclear clinical phenotypes. A genome-wide association study was conducted in 1100 cases and controls matched by vincristine dose and genetic ancestry, uncovering a statistically significant (p < 5.0 × 10−8) variant in MCM3AP gene that substantially increases the risk of neuropathy and 12 variants protective against neuropathy within/near SPDYA, METTL8, PDE4D, FBN2, ZFAND3, NFIB, PAPPA, LRRTM3, NRG3, VTI1A, ARHGAP5, and ACTN1. A follow-up pathway analysis reveals the involvement of four key pathways, including nerve structure and development, myelination, neuronal transmission, and cytoskeleton/microfibril function pathways. These findings present potential actionable genomic markers of vincristine neuropathy and offer opportunities for tailored interventions to improve vincristine safety in children with cancer. This study is registered with ClinicalTrials.gov under the title National Active Surveillance Network and Pharmacogenomics of Adverse Drug Reactions in Children (ID NCT00414115, registered on December 21, 2006).