Severe Adverse Drug Reactions Research Articles

Mining Real-World Big Data to Characterize Adverse Drug Reaction Quantitatively: Mixed Methods Study.

Adverse drug reactions (ADRs), which are the phenotypic manifestations of clinical drug toxicity in humans, are a major concern in precision clinical medicine. A comprehensive evaluation of ADRs is helpful for unbiased supervision of marketed drugs and for discovering new drugs with high success rates. In current practice, drug safety evaluation is often oversimplified to the occurrence or nonoccurrence of ADRs. Given the limitations of current qualitative methods, there is an urgent need for a quantitative evaluation model to improve pharmacovigilance and the accurate assessment of drug safety. In this study, we developed a mathematical model, namely the Adverse Drug Reaction Classification System (ADReCS) severity-grading model, for the quantitative characterization of ADR severity, a crucial feature for evaluating the impact of ADRs on human health. The model was constructed by mining millions of real-world historical adverse drug event reports. A new parameter called Severity_score was introduced to measure the severity of ADRs, and upper and lower score boundaries were determined for 5 severity grades. The ADReCS severity-grading model exhibited excellent consistency (99.22%) with the expert-grading system, the Common Terminology Criteria for Adverse Events. Hence, we graded the severity of 6277 standard ADRs for 129,407 drug-ADR pairs. Moreover, we calculated the occurrence rates of 6272 distinct ADRs for 127,763 drug-ADR pairs in large patient populations by mining real-world medication prescriptions. With the quantitative features, we demonstrated example applications in systematically elucidating ADR mechanisms and thereby discovered a list of drugs with improper dosages. In summary, this study represents the first comprehensive determination of both ADR severity grades and ADR frequencies. This endeavor establishes a strong foundation for future artificial intelligence applications in discovering new drugs with high efficacy and low toxicity. It also heralds a paradigm shift in clinical toxicity research, moving from qualitative description to quantitative evaluation.

Amikacin induced Stevens Johnson syndrome and toxic epidermal necrolysis overlap: a rare case report

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the most severe adverse drug reactions. They are characterized by necrosis and epidermal release in vesicobulosa skin, mucous orifice, and eyes, with more severe general symptoms. SJS/TEN-overlap syndrome is the term used to characterize situations where 10–30% of the body skin area is detached. TEN or SJS is one of the deadliest dermatological catastrophes. Despite being a rare condition, it frequently has a high death rate. Different types of purpuric macules or rounded patches with mucosal lesions are characteristic features of these type 3 hypersensitivity reactions. We are presenting a case of 50-year-old female patient brought to hospital on account of multiple black to red coloured raised lesions over body in the last 8 days. Patient was asymptomatic in the last 8 days after that patient noted red coloured lesions first over face followed by lower back, upper limb, lower limb followed by itching and Jiburning sensation all over the body. The patient had symptoms such as redness of eyes in the last 3-4 days, burning sensation and ulcers in mouth in the last 3-4 days. These symptoms developed day after she received amikacin. She was diagnosed with SJS-TEN overlap. This case highlights the precipitant of antibiotics for SJS. She was recovered completely after stopping the causative drug and treatment with Immunoglobulin with other symptomatic measures. The causative drug was found to be Amikacin and medicine taken for comorbid conditions like epilepsy, hypothyroidism and hypertension. Rarely, amikacin has been linked to a range of drug hypersensitivity reactions, including toxic epidermal necrolysis, Stevens-Johnson syndrome, and overlap between the two conditions.

Post-marketing surveillance of quetiapine fumarate extended-release tablets in patients with bipolar depression.

This study aimed to verify the real-world efficacy and safety of quetiapine fumarate extended-release tablets (Bipresso® 50 mg and 150 mg; marketing authorization holder is KYOWA Pharmaceutical Industry Co., Ltd., Osaka, Japan) in patients with bipolar depression. We performed a post-marketing surveillance with an observation period of 12 weeks. In the safety analysis group (n = 345), adverse drug reactions (ADRs) occurred in 111 patients (32.17%). The most common ADRs (>1%) were somnolence in 55 patients (15.94%), akathisia in 11 (3.19%), dizziness in 10 (2.90%), weight increase in 6 (1.74%), thirst in 5 (1.45%), and hypersomnia, constipation, and nausea in 4 patients each (1.16%). The only severe ADR was one patient of suicidal ideation, and "longer time since the onset of the first episode" (p = 0.011) and "presence of complications" (p < 0.001) were identified as significant risk factors for the occurrence of ADRs. In the efficacy analysis group (n = 265), the average changes from baseline in the total Montgomery-Åsberg Depression Rating Scale (MADRS) score were -7.3 ± 8.8, -12.2 ± 10.7, -16.8 ± 12.7, and -13.2 ± 12.7 points after 4, 8, and 12 weeks, and at the last evaluation, respectively. The mean MADRS total score decrease had no significant association with maximum daily dose, diagnosis, and presence or absence of prior or concomitant treatment for bipolar disorder with mood stabilizers/antipsychotics/antidepressants. The efficacy of quetiapine fumarate extended-release tablets was confirmed in clinical practice, and no new safety concerns or risks were identified.

Heparin-induced DRESS syndrome in a paediatric patient and successful anaesthetic management in cardiovascular bypass surgery: case report

BackgroundDrug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and systemic complications. DRESS diagnosis is challenging due to the variety of clinical presentations and symptom overlap with other conditions. The perioperative period in these patients requires precise pharmacological strategies to prevent complications associated with this syndrome. The treatment of DRESS induced by unfractionated heparin during cardiopulmonary bypass (CPB) surgery presents some challenges that must be considered when selecting an anticoagulant to avoid side effects. In this case, bivalirudin, a direct thrombin inhibitor, is indicated as an alternative to heparin in patients undergoing CPB. However, in contrast to heparin/protamine, there is no direct reversal agent for bivalirudin.Case presentationWe report the case of an 11-year-old male diagnosed with native aortic valve endocarditis and thrombosis in his left lower extremity. During valvular replacement surgery, systemic unfractionated heparin was administered. Postoperatively, the patient developed fever, eosinophilia and pruritic rash. Warm shock and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels followed, leading to the diagnosis of DRESS syndrome. Treatment with methylprednisolone resulted in complete resolution of symptoms. Seven years later, the patient was readmitted due to insufficient anticoagulation and a thrombus in the prosthetic aortic valve, presenting a recurrent DRESS episode due to the administration of unfractionated heparin, which was later replaced with low-molecular-weight heparin during hospitalization. Treatment with corticosteroids and antihistamines was initiated, resulting in the resolution of this episode. Ultimately, the patient required the Ross procedure. During this intervention the anticoagulation strategy was modified, unfractionated heparin was replaced with bivalirudin during the procedure and fondaparinux was administered during the postoperative period. This resulted in stable transaminases levels and no eosinophilia.ConclusionThe severity of DRESS Syndrome underscores the importance of early recognition, heightened monitoring, and a comprehensive approach tailored to each patient’s needs. This particular case highlights the significance of this approach and may have a substantial clinical impact since it provides alternatives to heparin, such as bivalirudin and fondaparinux, in the anticoagulation strategy of CPB for patients who have a hypersensibility reaction to this medication; thus, enhancing clinical outcomes by minimizing risks linked to adverse drug reactions.

Adverse reactions of piperacillin: A literature review of case reports.

This study aimed to summarize case reports of adverse drug reactions (ADRs) caused by piperacillin and explore their effects on human organs in real-world settings. Case reports of piperacillin ADRs were collected by searching databases such as PubMed, Embase, Web of Science, CNKI, WanFang, and VIP from inception to December 2022. A total of 170 patients were ultimately included. The results revealed that ADRs caused by piperacillin were primarily associated with the entire body, followed by the blood system, skin and soft tissues, and the nervous system. The most frequently reported cases included anaphylactic shock, drug fever, rash, and thrombocytopenia. The most severe ADRs were identified as anaphylactic shock and bullous epidermal necrolysis. Furthermore, a comparison was made between systemic adverse reactions caused by piperacillin as a single drug and two composite preparations of piperacillin/β-lactamase inhibitor. ADRs not mentioned in the instructions included convulsions or hallucinations and Kounis syndrome (KS). This review suggests that the most severe ADRs associated with piperacillin are toxic epidermal necrolysis and anaphylactic shock. Rare ADRs caused by piperacillin, such as myoclonic jerks, hallucinations, and KS, were identified. The most common symptom with domestic preparations of piperacillin/sulbactam and piperacillin sodium was dyspnea.

ADVERSE DRUG REACTIONS OF BACLOFEN, NALTREXONE, AND ACAMPROSATE IN PATIENTS HAVING ALCOHOL DEPENDENCE: A CROSS-SECTIONAL PHARMACOVIGILANCE STUDY

Objectives: The research aims to investigate the prevalence and patterns of adverse drug reactions (ADRs), gauge the severity of these reactions, establish causality in ADR cases, and assess the preventability of such adverse reactions. Methods: ADR information was gathered through personal interviews with patients or their relatives. Causality was assessed using the Naranjo algorithm, and a modified Hartwig and Siegel Severity Assessment Scale was used for estimating the severity of ADR. ADRs were grouped into various preventability categories based on the modified Schumock and Thornton criteria. Results: The total number of patients evaluated in the baclofen, naltrexone, and acamprosate groups was 65, 28, and 42, respectively. The most commonly reported adverse events with baclofen were nausea (31.25%), followed by fatigue (18.75%) and headache (12.50%). The majority of patients receiving acamprosate reported nausea (57.14%), followed by diarrhea (28.57%). Patients receiving naltrexone most commonly reported nausea (35.71%), followed by abdominal pain (21.43%) and headache (14.28%). Conclusion: This study shed light on the prevalence, severity, causality, and preventability of ADRs associated with anti-craving agents used to treat patients with alcohol withdrawal syndrome, providing valuable insights into the safety profiles of these medications.

Precision in Language Regarding Geographic Region of Origin in Severe Cutaneous Adverse Drug Reaction Research

Precision in Language Regarding Geographic Region of Origin in Severe Cutaneous Adverse Drug Reaction Research

Healthcare Professionals’ Attitudes towards Adverse Drug Reactions Reporting in Primary Healthcare Settings: A Cross-sectional Survey

Background: Spontaneous Adverse Drug Reactions (ADRs) reporting is a key to improving the post-marketing safety of medicines. The important factor of under-reporting is lack of awareness for the purpose of ADRs monitoring and reporting. Spontaneous reporting is performed by the patients or consumer to the healthcare professionals and/or industry, then the healthcare facilities and industry should report the suspected ADRs to the National Agency of Drugs and Food Control (NADFC). To date, there is a lack information and study about attitudes on ADRs reporting by healthcare professionals (HCPs), especially in primary healthcare settings.Objectives: The aim of this study was to identify the attitudes towards ADRs reporting by healthcare professionals (HCP).Methods: This research was survey study with cross-sectional design, from November 2022-March 2023. The questionnaire, that have been validated and reliable, was distributed to 3 primary healthcare facilities. demographic data questions (6 items), experiences (3 items), knowledge (4 items), and motives for reporting (1 item).Results: Total 39 HCPs completed the survey, including 14 nurses, 9 midwifes, 3 general physicians, 3 pharmacists, and 10 other professions. Most of respondents were women (84.6%), and mostly the HCPs have been working for ≥5 years (74.3%). Among 39 respondents, only 1 pharmacist have a good attitude about ADRs reporting. The other HCPs had a lack of knowledge and safety awareness. The dominant motives for reporting the ADRs was serious or severe ADRs (39.4%) and the assurance of causality assessment by suspected drugs (15.4%).Conclusion: In conclusion, the HCPs in primary healthcare settings had poor attitudes towards ADRs reporting.

Clinical Pharmacist Counselling Improves Long-term Medication Safety and Patient-reported Outcomes in Anti-TNF-treated Patients With Inflammatory Bowel Diseases: The Prospective, Randomized AdPhaNCED Trial.

Antitumor necrosis factor (anti-TNF) antibody treatment has led to marked improvements in the management of patients with inflammatory bowel diseases (IBDs). Nevertheless, anti-TNF therapy is associated with potential adverse drug reactions (ADRs). Our prospective, randomized trial investigated the effect of intensified clinical pharmacist counselling in a multidisciplinary team on medication safety in anti-TNF-treated IBD patients. Patients with IBD with ongoing anti-TNF treatment were enrolled in our tertiary center AdPhaNCED trial and randomized to either receive conventional standard of care (control group) or additional clinical pharmacist counselling (intervention group) over 12 months. The primary end point consisted of the number and severity of ADRs associated with anti-TNF therapy. Secondary end points included patient satisfaction with medication information and medication safety. One hundred twenty-seven IBD patients were included in this study. Anti-TNF-related ADRs were significantly lower in the intervention compared with the control group (0.20 vs 0.32 [mean] ADR/patient/month, P = .006) after 12 months. The risk of more severe ADRs (Common Terminology Criteria for Adverse Events [CTCAE] grade ≥2) was significantly higher in the control compared with the intervention group (hazard ratio, 0.34; P = .001). The probability of ADR resolution (hazard ratio, 2.02; P < .001) and patient satisfaction with medication information (14.82 vs 11.60; P < .001) were significantly higher in the intervention group compared with the control group. Our study results demonstrate that intensified pharmacist counselling significantly reduces the occurrence and severity of therapy-related ADRs and improves patient satisfaction. Clinical pharmacists should therefore be part of a holistic approach to IBD care delivered by a multidisciplinary team.

Monoclonal Antibodies Targeting CGRP to Treat Vestibular Migraine: A Rapid Systematic Review and Meta-Analysis

AbstractVestibular migraine (VM), a subtype of migraine characterized by vestibular symptoms, poses a significant diagnostic and therapeutic challenge. This study aimed to evaluate the effectiveness of monoclonal antibodies targeting Calcitonin Gene Related Peptide (CGRP) in the treatment of VM. Therefore, we conducted a rapid systematic review and meta-analysis following PRISMA and Cochrane guidelines. A search of databases (PubMed, Scopus, Cochrane and Google Scholar) was performed in October 2023. Inclusion criteria required original research articles focusing on patients diagnosed with VM and utilizing CGRP-targeting monoclonal antibodies. We performed qualitative assessments of study design, patient characteristics, and outcomes and, for studies with comparable outcome measures, a meta-analysis was conducted. Our search yielded four relevant studies, including cohort studies and a case report, totaling 99 patients. Proper vestibular instrumental tests were employed in half of the studies. Overall, the included studies reported significant improvements in VM symptoms. Our quantitative analysis, focused on migraine symptoms, demonstrated a substantial reduction in Monthly Days with Migraine at 6 months following treatment. No severe adverse drug reactions were reported. In conclusion, this rapid systematic review and meta-analysis provide preliminary evidence for the efficacy of CGRP-targeting monoclonal antibodies in treating Vestibular Migraine. However, the absence of randomized controlled trials and variations in study designs and diagnostic criteria introduce some limitations. Further research is needed, including controlled trials, to establish a more robust evidence base. Nonetheless, this treatment approach offers hope for the effective management of VM, potentially enhancing the well-being of affected individuals and reducing their associated disability.

NEURAL NETWORK-BASED ADVERSE DRUG REACTION PREDICTION USING MOLECULAR SUBSTRUCTURE ANALYSES

Objective: This study aims to enhance early detection and prediction by exploiting drug molecular substructures, overcoming challenges posed by limited authentic patient data in the medical domain. Methods: The study implemented a neural network approach to optimize molecular fingerprint algorithms and employed various machine learning algorithms for predictions. Additionally, the study identified and extracted substructures associated with severe Adverse Drug Reactions (ADRs), validating their presence within drug structures through a comparison with a random set of drug structures. Predictions were made for specific molecular structures, and results were validated using clinical evidence from the literature. Results: Optimized molecular fingerprint algorithms and diverse machine-learning models yielded promising outcomes. The Area Under Curve (AUC) value for the fingerprint dataset was obtained at approximately 65%, and integrating it with patient data significantly improved the performance by about 30%. Substructure analysis pinpointed key components linked to severe ADRs, reinforcing the predictive prowess of the model. Predictions for specific molecular structures were corroborated using clinical evidence from the literature, fortifying the credibility of the proposed approach. Conclusion: In conclusion, this research effectively tackles challenges in the early detection and prediction of ADRs by leveraging machine learning algorithms, focusing on drug molecular substructures. The optimized model, incorporating both fingerprint and patient datasets, demonstrated significant improvements in predictive performance. Identifying and validating substructures linked to severe ADRs contribute to the model's reliability. The study's findings are vital for advancing drug safety and laying the groundwork for further strides in predictive modeling within the medical domain.

Evaluation of severe adverse cutaneous drug reactions in patients admitted to tertiary care center: A cross-sectional study.

Adverse cutaneous drug reactions (ACDRs) are common and potentially life-threatening, while also hindering patient compliance to medications. Given the regional differences in patterns and prevalence of ACDRs, it is important to study the epidemiology, as well as the clinical and outcome patterns of patients with ACDRs in Iran. This cross-sectional study on ACDRs was conducted among hospitalized patients in a referral university hospital in the city of Isfahan, Iran. The patients' demographics, clinical information, and outcomes, including age, gender, past medical history, medication history, drug reaction with eosinophilia and systemic symptoms (DRESS) diagnosis, Steven-Johnson Syndrome (SJS) diagnosis, toxic epidermal necrosis (TEN) diagnosis, treatment regimen (steroids or intravenous immunoglobulin [IVIG]) and outcome information, including intensive care requirements, severe medical complications, or death, were obtained from medical records. A total of 195 patients with a mean age of 40 years and consisting of 61% females were included. Carbamazepine, lamotrigine, sodium valproate, and phenytoin are the most commonly reported medications. Rate of complications was 45% with DRESS, SJS, and TEN diagnosed in 26%, 47%, and 19%, respectively. Treatment was carried out with steroids and IVIG in 81% and 19%, respectively. Among patients, 15% required intensive care and 5% died. Diagnosis of TEN, older age, and baseline heart disease were predictors of mortality. Patients with SJS were younger and more likely to be males, and they were more likely to have eye complications. On the other hand, patients with the diagnosis of TEN were more likely to receive IVIG and intensive care, and had a higher mortality rate. Our study provides insight into the demographics and clinical patterns of Iranian patients with ACDRs. This will help in predicting rates of complications, treatments, and outcomes in patients and therefore make proper management decisions.

Exploring Safety in Gender-Affirming Hormonal Treatments: An Observational Study on Adverse Drug Events Using the Food and Drug Administration Adverse Event Reporting System Database.

People with gender dysphoria are treated with hormone therapy for gender reassignment. The indication of this therapy was initially for the opposite sex, and information on potential adverse drug reaction (ADR) is lacking. To describe ADR associated with gender transition medication in transgender individuals reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Data from the FAERS database up to June 2023 were examined, focusing on reports of gender transition medication use in the context of gender dysphoria. The ADRs were categorized using the Medical Dictionary for Regulatory Activities at both Preferred Term and System Organ Class (SOC) levels. Descriptive statistics summarized report counts, medication types, indications, and ADR severity. For individuals assigned female at birth undergoing gender transition to male (transgender men), 82 reports (230 ADRs) were analyzed, with an average age of 29.5 years. Transgender hormonal therapy was cited in 72% of reports, predominantly from the United States (67.1%). A striking 88% were categorized as serious ADRs, primarily SOC injury, poisoning, and procedural complications (26.5%), followed by psychiatric disorders (14.8%) and nervous system disorders (12.2%). Among those assigned sex male at birth transitioning to female (transgender women) (81 reports, 237 ADRs), mean age was 33.3 years, with 58% indicating use for gender dysphoria. A significant proportion (53.6%) were serious ADRs, primarily SOC: injury, poisoning, and procedural complications (26.6%). The FAERS data reveal significant ADRs in transgender individuals using hormone therapy, sometimes unintended for their recipient gender. Population-level studies are crucial to enhance transgender health care. Spontaneous surveillance databases like FAERS illuminate off-label ADRs, urging health care providers to approach hormone therapies with informed caution.

Serum Levels of Interleukin-1 Beta are Decreased in Patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis at the Time of Hospitalization

BACKGROUND: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions. Some immunological and genetic factors are believed to be involved in the pathogenesis of the disease, including tumor necrotic factor-alpha, interferon-gamma, and interleukin (IL)-17. IL-1β is one of the most prominent cytokines associated with the innate immune response. AIMS: The study aimed to evaluate the serum level of IL-1β in SJS/TEN and the relation between it and the progress of SJS/TEN. METHODS: This was a cross-sectional descriptive study conducted at the National Hospital of Dermatology and Venereology, in Hanoi, Vietnam, from October 2017 to September 2019. 48 SJS/TEN patients, 43 erythema multiforme (EM) patients, and 20 healthy controls (HCs) participated. IL-1β levels were measured using the fluorescence covalent microbead immunosorbent assay (ProcartaPlex Immunoassay Panels kit, Thermo Fisher Scientific, USA). The Mann–Whitney U test was used to compare serum IL-1β levels. The Wilcoxon tests were used to compare quantitative variables before and after the treatment. Differences were considered to be statistically significant at p &lt; 0.05. RESULTS: 19 SJS patients (39.5%) and 29 TEN patients (60.5%) participated in our study. The mean age was 49.3 years; the range was 19–77 years (47.9% males; 52.1% females). The most common causative drugs were traditional medicine (29.1%), carbamazepine (12.5%), and allopurinol (12.5%). On the day of hospitalization, the mean serum level of IL-1β of the SJS/TEN group was 26.4 ± 81.7 pg/mL, ranging from 0.5 pg/mL to 447 pg/mL. This level was significantly lower than that of the HCs group (p &lt; 0.001) but not lower than that of the EM group. The mean serum level of IL-1β in the SJS/TEN patients on the day of hospitalization was 26.4 ± 81.7 pg/ml, higher than that on the day of re-epithelialization (1.9 ± 5.6 pg/mL) and the difference was statistically significant with p &lt; 0.01. CONCLUSION: Serum IL-1β level in SJS/TEN patients is lower than in HCs. It is not a good biomarker to differentiate SJS/TEN from EM.

Incidence and Predictors of Severe Adverse Drug Reactions among Patients on Antiretroviral Drugs in Harari Regional State, Eastern Ethiopia.

The introduction of combination antiretroviral therapy improves the quality and longevity of people living with HIV/AIDS. However, adverse drug reactions associated with antiretroviral therapy compromise the resulting benefits and have been reported differently worldwide, including Ethiopia. Severe adverse drug reactions are one of the major public health concerns for the reason that they can potentially impede the benefit of antiretroviral therapy and put the patient's survival at risk. Despite many successes achieved with the introduction of the combined antiretroviral therapy, the majority of the patients on antiretroviral therapy experience adverse drug reactions associated with the drugs. Consequently, little is known about the problem in the current study area. This is, therefore, to study incidence and predictors of severe adverse drug reactions among patients on antiretroviral drugs in the Harari region, Eastern Ethiopia. The aim of this study was to assess the incidence and predictors of severe adverse drug reactions among patients on antiretroviral therapy from February 25, 2022, to March 25, 2022, in the Harari region, Eastern Ethiopia. A hospital-based retrospective cohort study was conducted among 449 randomly selected medical records of people living with HIV on first-line antiretroviral therapy. Collected data were entered into EpiData version 3.1 and exported to STATA version 15 for analysis. Kaplan-Meier survival curve with log-rank test was used to compare survival curves for categorical independent variables. A p value ≤0.05 was declared as significant, and an adjusted hazard ratio was used to report the effect size using the multivariate Cox proportional hazard model. The overall incidence density of the severe adverse reactions was 7.22 per 1000 months (95% CI: 5.5, 9.6). After adjusting for all potential confounders using multivariable Cox proportional hazard ratio, advanced clinical diseases (AHR = 3.44; 95% CI: 1.54, 7.65), HIV/tuberculosis confections (AHR = 2.38; 95% CI: 1.23, 4.62), and being female (AHR = 3.12; 95% CI: 1.57, 6.18) were significantly associated with the experience of severe adverse drug reactions. In this study, the incidence of severe adverse reactions was consistent with the previous studies, and advanced World Health Organization (WHO) clinical stage, HIV/TB confection, and being female were the independent predictors of the severe adverse drug reactions.

Pediatric drug reaction with eosinophilia and systemic symptoms: A 12-year retrospective study in a tertiary center.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and severe adverse drug reaction involving multiple organs. Data on DRESS syndrome among children are currently limited. The purpose of this study was to determine the clinical features, causative drugs, systemic organ involvement, laboratory findings, disease severity score, and treatment outcomes in pediatric DRESS patients. The medical records of all pediatric DRESS patients, based on the RegiSCAR diagnostic criteria and admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand from January 2010 to December 2021, were reviewed. Twenty-two cases were identified (males 54.5%) with a median age of 9.5 years. Anticonvulsants (54.5%) and antibiotics (27.3%) were the leading culprit drugs. Skin rash was reported in all cases, followed closely by liver involvement (95.5%). Eosinophilia and atypical lymphocytosis were identified in 54.5% and 31.8% of cases, respectively. The median latency period was 17.5 days. Liver enzyme elevation was detected at an average onset of 20.0 days and hepatocellular type was the most common pattern of liver injury. Nineteen patients (86.4%) were treated with systemic corticosteroids with prednisolone being the most prescribed medication. One case developed Graves' disease after DRESS and multiple relapses of DRESS. One case (4.5%) died due to refractory status epilepticus that was unrelated to DRESS. Anticonvulsants were the major cause of DRESS in pediatric patients. High suspicion for DRESS is crucial in patients receiving these drugs and presenting with fever, rash, and internal organ involvement.

Identification and Functional Assessment of Eight CYP3A4 Allelic Variants *39-*46 Detected in the Chinese Han Population.

Cytochrome P450 3A4 (CYP3A4), a key enzyme, is pivotal in metabolizing approximately half of the drugs used clinically. The genetic polymorphism of the CYP3A4 gene significantly influences individual variations in drug metabolism, potentially leading to severe adverse drug reactions (ADRs). In this study, we conducted a genetic analysis on CYP3A4 gene in 1163 Chinese Han individuals to identify the genetic variations that might affect their drug metabolism capabilities. For this purpose, a multiplex polymerase chain reaction (PCR) amplicon sequencing technique was developed, enabling us to perform the genotyping of CYP3A4 gene efficiently and economically on a large scale. As a result, a total of 14 CYP3A4 allelic variants were identified, comprising six previously reported alleles and eight new nonsynonymous variants that were nominated as new allelic variants *39-*46 by the PharmVar Association. Further, functional assessments of these novel CYP3A4 variants were undertaken by coexpressing them with cytochromes P450 oxidoreductase (CYPOR) in Saccharomyces cerevisiae microsomes. Immunoblot analysis indicated that with the exception of CYP3A4.40 and CYP3A4.45, the protein expression levels of most new variants were similar to that of the wild-type CYP3A4.1 in yeast cells. To evaluate their catalytic activities, midazolam was used as a probe drug. The results showed that variant CYP3A4.45 had almost no catalytic activity, whereas the other variants exhibited significantly reduced drug metabolism abilities. This suggests that the majority of the CYP3A4 variants identified in the Chinese population possess markedly altered capacities for drug metabolism. SIGNIFICANCE STATEMENT: In this study, we established a multiplex polymerase chain reaction (PCR) amplicon sequencing method and detected the maximum number of new CYP3A4 variants in a single ethnic population. Additionally, we performed the functional characterizations of these eight novel CYP3A4 allele variants in vitro. This study not only contributes to the understanding of CYP3A4 genetic polymorphism in the Chinese Han population but also holds substantial reference value for their potential clinical applications in personalized medicine.

Clinico-Epidemiological Profile and Treatment Outcome of Severe Cutaneous Adverse Drug Reactions in the Paediatric Age Group of 0 to 18 Years: A Retrospective Cohort Study from Southern India

Introduction: The paediatric population is prone to developing cutaneous adverse drug reactions. However, the incidence of Severe Cutaneous Adverse Drug Reactions (SCAR) is rare in this age group, with few studies describing such reactions in detail. Aim: To describe the clinico-epidemiological factors, drug profile, laboratory parameters, and treatment outcomes of SCAR in children admitted to a tertiary care centre in South India. Materials and Methods: A retrospective cohort study was carried out over a 10-year period, including paediatric patients (0-18 years) admitted to Dermatology, Medicine, and Paediatric wards in the tertiary care centre. Demographic details, suspected drugs, comorbidities, personal and family history of drug reactions, physical examination, laboratory parameters, treatment received along with its duration, and the state of morbidity and mortality were recorded. SPSS version 18.0 was used for analysis. Descriptive statistics were used to summarise the demographics and clinical characteristics of the patients. Results: Among all the patients admitted with SCAR, 27 (15%) belonged to the paediatric age group. The median age was 15 years, and the female-to-male ratio was 1.25. Nineteen (70.3%) were diagnosed with Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), and eight (29.6%) were diagnosed with Drug Reaction with Eosinophilia and Systemic Symptom (DRESS). There were no cases of Acute Generalised Exanthematous Pustulosis (AGEP). The most common class of drugs implicated was antiepileptics (62.8%). Two patients (7%) had a family history of drug reactions. All patients had mucosal involvement. The majority of the children responded to intravenous steroids, and two required additional intravenous immunoglobulin injections for clinical improvement. All cases were cured with no mortality or long-term sequelae. Conclusion: The incidence of SCAR in the paediatric age group is significant. Anticonvulsants, particularly phenytoin, carbamazepine, and lamotrigine, need to be used with caution in this age group. Prompt diagnosis and treatment with systemic steroids can reduce mortality, morbidity, and long-term sequelae.

Severe cutaneous adverse drug reactions: incidence, clinical characteristics, treatment, and outcome in pediatric patients.

Severe cutaneous adverse drug reactions (SCARs) can cause significant morbidity and mortality. Clinical data regarding such conditions is still limited in the pediatric population. To investigate the incidence, clinical characteristics, treatment, and outcome of SCARs in Thai pediatric patients. This retrospective study enrolled 52 patients aged less than 18 years who were diagnosed with acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or SJS/TEN overlap during January 2005 to August 2021 at Siriraj Hospital. SCARs were slightly more prevalent in females than in males (51.9% vs. 48.1%). Median age at diagnosis was 97 months, and median length of hospital stay was 11 days. DRESS, SJS, TEN, AGEP, and SJS/TEN overlap was found in 44.2%, 36.5%, 9.6%, 5.8%, and 3.8%, respectively. The most common etiologies were antimicrobial agents (40.3%) and anticonvulsants (35.5%). Target lesions, vesicobullous lesions, purpura, positive Nikolsky's sign, and skin tenderness were significant in blistering SCARs. Hematologic (84.6%) and hepatic (65.5%) manifestations were common. Treatment varied according to the clinical features of each condition. Systemic corticosteroids showed some benefit in SJS/TEN. One patient diagnosed with TEN died for an overall SCARs mortality rate of 1.9%. The unique characteristics of SCARs described herein can lead to timely and accurate diagnosis and proper management.

Pattern of adverse drug reactions to commonly prescribed antibiotics in a tertiary care hospital

Background: Antibiotics have been one of the most significant discoveries in the history of medicine, as they saved countless lives and prevented many serious complications from bacterial infections. Antibiotics are usually safe and effective in treating bacterial infections but can result in adverse drug reactions (ADRs) in some patients. Antibiotics are the most common class of drugs which implicate a greater number of ADRs, because of overuse and misuse of antibiotics, antibiotic resistance, and decreased efficacy. Aims and Objectives: The aims and objectives of the study are to determine clinical symptoms, causality, and severity of antibiotic-associated ADRs. Materials and Methods: A retrospective study was carried out from January 2021 to June 2022; data were collected from Adverse Drug Monitoring Center, GMC/Government General Hospital, Guntur. Prior Institutional Ethics Committee Approval and Permission from Indian Pharmacopoeia Commission, Ghaziabad, were taken. The collected reports were analyzed for ADR pattern, drug groups, causality, and severity. Descriptive statistics were used. Results: Out of 847 ADRs reported, 119 (14%) ADRs were related to antibiotics. The majority of ADRs (65%) were reported in males. A greater number of ADRs were reported in mean age group 31–40 years. Anti-tubercular drugs (27%) were the most commonly implicated antibiotics followed by cephalosporins (22%). Most commonly affected system was cutaneous system (45%) followed by gastrointestinal system (21%). Most common ADRs reported were pruritus (20%), followed by rash (14%). 93% of ADRs were possible and 7% were probable. 87% of ADRs were mild, 12% were moderate, and 2% were severe ADRs. Conclusion: ADRs can be prevented by taking proper action at an early stage. Implementation of antibiotic guideline policy for the hospital and strict adherence to it should be ensured to promote their rational and safe use.