A systematic assessment of robustness in CNS safety pharmacology.

BACKGROUND AND PURPOSE: Irwin tests are key preclinical study elements for characterising drug-induced neurological side effects. This multicentre study aimed to assess the robustness of Irwin tests across multinational sites during three stages of protocol harmonisation. The projects were part of the Enhanced Quality in Preclinical Data framework, aiming to increase success rates in transition from preclinical testing to clinical application. EXPERIMENTAL APPROACH: Female and male NMRI mice were assigned to one of three groups (vehicle, MK-801 0.1 and 0.3 mg kg-1). Irwin scores were assessed at baseline and multiple times following intraperitoneal injection of MK-801 using local protocols (Stage 1), shared protocols with harmonised environmental design (Stage 2) and fully harmonised Irwin scoring protocols (Stage 3). KEY RESULTS: The analysis based on the four functional domains (motor, autonomic, sedation and excitation) revealed substantial data variability in Stages 1 and 2. Although there was still marked overall heterogeneity between sites in Stage 3 after complete harmonisation of the Irwin scoring scheme, heterogeneity was only moderate within functional domains. When comparing treatment groups versus vehicle, we found large effect sizes in the motor domain and subtle to moderate effects in the excitation-related and autonomic domains. CONCLUSION AND IMPLICATIONS: The pronounced interlaboratory variability in Irwin datasets for the CNS-active compound MK-801 needs to be carefully considered when making decisions during drug development. While environmental and general study design had a minor impact, the study suggests that harmonisation of parameters and their scoring can limit variability and increase robustness.

Chloroquine-Induced Fixed Drug Eruption: A Case Report.

Recurrent erythematous rashes in the same anatomical site are a feature of a disorder known as fixed drug eruption (FDE). We describe a rare instance of a fixed eruption in a 70-year-old woman who had recurrent skin lesions at the same locations due to the use of chloroquine. This case demonstrates the timely and precise identification of an FDE, which resulted in the offending medication being stopped and the symptoms clearing up when topical steroids were used. This case study underscores the significance of attentive healthcare practices and the vital impact that thorough, individualized treatment plays in improving the patient's condition.

Adverse Drug Reactions and Predictors of Medication Adherence in Patients with Prostate Cancer.

Background: Adherence to therapy with prostate cancer medicines is critical for delaying the progression of disease and enhancing health outcomes. Objectives: To determine patients' medication adherence, the predictors of adherence, and the frequency and types of adverse drug reactions (ADRs) in persons with prostate cancer. Methods: A serial entry-point cross-sectional study of patients with prostate cancer was conducted in 3 cancer hospitals in Nigeria over a 12-month period (January 7, 2022, to January 3, 2023). Data on medication adherence were self-reported by patients, and data on ADRs were obtained from hospital records. Descriptive and inferential statistical analyses were performed, and p less than 0.05 was considered statistically significant. Results: Of the 133 study participants, most 112 (84.2%) reported high medication adherence. The cost of drugs was the most frequently reported potential barrier to adherence (n = 63, 47.4%). Adherence was significantly dependent on family history of cancer (df = 3, F = 4.557, p = 0.005) and health-related quality of life (HRQOL) (ß = 0.275, T = 2.170, p = 0.032) but not illness perception (ß = 0.046, T = 0.360, p = 0.72). Adverse events were observed in 36 participants (27.1%) and were deemed to be "possible ADRs" (n = 19, 53%) or "probable ADRs" (n = 17, 47%); all were nonpreventable and expected (100%), and most (n = 31, 86%) were within the level 1 category of severity. Loss of erection and low libido was the most frequently reported ADR (n = 14, 39%). Conclusions: In this study, medication adherence was high, with cost being a potential barrier to adherence. Family history of cancer and HRQOL significantly predicted medication adherence. The medications were well tolerated, and observed ADRs had minor severity. Policies targeting the reduction of cost-related factors for prostate cancer medications are essential.

Contexte: L'observance thérapeutique quant à la prise de médicaments contre le cancer de la prostate est essentielle pour retarder la progression de la maladie et améliorer les résultats en matière de santé. Objectifs: Déterminer l'observance thérapeutique des patients, les facteurs prédictifs de l'observance ainsi que la fréquence et les types d'effets indésirables du médicament chez les personnes atteintes d'un cancer de la prostate. Méthodologie: Une étude transversale en série a été menée auprès de patients atteints d'un cancer de la prostate dans trois hôpitaux spécialisés dans le traitement du cancer au Nigéria sur une période de 12 mois (du 7 janvier 2022 au 3 janvier 2023). Les patients ont eux-mêmes consigné les données relatives à l'observance thérapeutique et les données concernant les effets indésirables ont été obtenues à partir des dossiers de l'hôpital. Des analyses statistiques descriptives et inférentielles ont été réalisées, où une valeur de p inférieure à 0,05 était considérée comme significative d'un point de vue statistique. Résultats: Des 133 participants à l'étude, la plupart (112, 84,2 %) ont déclaré une forte observance thérapeutique. Le coût des médicaments était l'obstacle potentiel à l'observance le plus fréquemment invoqué (n = 63, 47,4 %). L'observance dépendait significativement des antécédents familiaux de cancer (df = 3, F = 4,557, p = 0,005) et de la qualité de vie liée à la santé (QVLS) (ß = 0,275, T = 2,170, p = 0,032), mais pas de la perception de la maladie (ß = 0,046, T = 0,360, p = 0,72). Des événements indésirables ont été observés chez 36 participants (27,1 %) et ont été considérés comme des « effets indésirables du médicament possibles ¼ (n = 19, 53 %) ou des « effets indésirables du médicament probables ¼ (n = 17, 47 %); tous étaient inévitables et attendus (100 %), et la plupart (n = 31, 86 %) relevaient de la catégorie de gravité de niveau 1. La perte d'érection et la faible libido étaient les effets indésirables les plus fréquemment signalés (n = 14, 39 %). Conclusions: Dans cette étude, l'adhésion au régime médicamenteux était élevée, le coût étant un obstacle potentiel à l'observance. Les antécédents familiaux de cancer et la QVLS prédisaient de manière significative l'observance thérapeutique. Les médicaments étaient bien tolérés et les effets indésirables du médicament observés n'étaient pas fort graves. Il est essentiel de mettre en place des politiques visant à réduire les facteurs liés au coût des médicaments contre le cancer de la prostate.

Poisoning and envenomation linkage to evaluate outcomes and clinical variation in Australia (PAVLOVA): a longitudinal data-linkage cohort of acute poisonings, envenomations, and adverse drug reactions in New South Wales, Australia, 2011-2020.

INTRODUCTION: Poisoning is a leading cause of morbidity and mortality that is increasing in many countries. Better data are needed to understand epidemiology and outcomes of poisoning. This work describes a new poisoning data linkage cohort in New South Wales, Australia (population approximately 8 million). METHODS: This is a longitudinal health record linkage, 2011-2020, including data from: ambulance call-outs, emergency department presentations, hospital admissions, death registrations, the poisons centre, and four tertiary toxicology units. Individuals with poisoning, venomous animal/plant exposures, or adverse drug reaction events were included. RESULTS: There were 845,217 linkable events relating to 400,642 ambulance, 688,484 emergency department, 682,013 admission, 40,456 toxicology, and 11,879 death records. There were 572,841 people with events; the median age at the time of first event was 57 years, and 51.9% were female. Events leading to patient admission were most commonly adverse drug reactions (n = 511,263), intentional poisonings (n = 68,646), unintentional poisonings (n = 54,840) and animal/plant exposures (n = 11,092). Demographics varied by cause: intentional poisoning (median age 33 years, 61.7% female); unintentional poisoning/animals/plants (median age 43 years, 45% female); and adverse drug reactions (median age 70 years, 54% female). Adolescent females had highest rates of intentional poisoning, while unintentional poisoning had a bimodal distribution, highest in children <5 years old and males aged 20 to 50 years. Substance use disorders were documented comorbidities for 44% of intentional poisoning, 29% of unintentional poisoning, and 13% of adverse drug reaction-related admissions; mood disorders were documented for 54%, 17% and 10% of these admissions, respectively. DISCUSSION: Poisonings and hospitalised adverse drug reactions are common in New South Wales, affecting approximately 8% of the population in 10 years. This linkage improves understanding of poisoning risks and outcomes in Australia. CONCLUSIONS: This novel data linkage provides a unique opportunity to study poisoning across multiple settings for an individual over an extended period.

Drug-induced pancreatitis: study of 38 patients. / Pancreatitis inducidas por fármacos: estudio de 38 pacientes.

INTRODUCTION: Acute pancreatitis (AP) is an inflammatory disease with multiple etiologies, and the emergence of complications. Between 0.1-5% of cases are attributed to drugs. The absence of specific characteristics complicates the diagnosis and treatment of drug-induced AP. Reviewing patients admitted with the diagnosis of drug-induced AP can provide information and improve its management. PATIENTS AND METHODS: This is a descriptive, observational, and retrospective study. All patients admitted to the Hospital Universitari de Bellvitge between June 2007 and March 2023 with suspected drug-induced AP were included. The data were obtained from the hospital pharmacovigilance program database. RESULTS: Thirty-eight patients with suspected drug-induced AP were identified, representing 0.62% of all adverse drug reactions (n=6.085). Of these, 65.8% (n=25) had a single suspected drug. The median latency period for the onset of adverse drug reactions was 160.5 days (IQR: 18-582 days), and the median hospital stay was 5 days (IQR: 3-7 days). Fifty-nine suspected drugs were identified, involving 26 active principles. Azathioprine and atorvastatin were the most frequent, with 9 cases each (15.2%), followed by enalapril with 8 cases (13.6%). Drug etiology was assessed in 23 cases (60.5%), and the suspected drug was discontinued in all cases. There was one fatal case documented (2.63%). CONCLUSION: This study can contribute to better understanding of drug-induced pancreatitis episodes. We propose a diagnostic algorithm that includes the assessment of the drug as a possible cause.

Naproxen adjunct to fluoxetine for moderate-to-severe obsessive-compulsive disorder: A randomized, double-blind, placebo-controlled trial.

AIM: Current treatments for obsessive-compulsive disorder (OCD) encounter resistance and limiting adverse events, necessitating novel therapeutic strategies. This study aimed to investigate the benefits of naproxen, a medication with effects on inflammation and neuronal function, on OCD. METHODS: One hundred and four OCD outpatients with a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score of >21 were equally assigned to receive fluoxetine plus either naproxen 250 mg or matched placebo q12hr. Patients were assessed using the Y-BOCS by recording the subscale scores at baseline and weeks 5 and 10 to evaluate efficacy. They were also assessed in terms of tolerability. RESULTS: Data from 96 patients were analyzed. The baseline characteristics were comparable between the groups. There were significant time-treatment interaction effects on the obsession subscale ( η P 2 $$ {\eta}_P^2 $$ = 0.055) and total ( η P 2 $$ {\eta}_P^2 $$ = 0.043) scores of Y-BOCS. Reductions in the obsession subscale and total scores of Y-BOCS were significantly greater in the fluoxetine plus naproxen group until the endpoint (Cohen's d = 0.560 and Cohen's d = 0.477, respectively). However, the difference in compulsion subscale score changes between the groups was not significant. Respondents with a reduction of ≥35% in Y-BOCS total scores were significantly more in the fluoxetine plus naproxen group (80.0% versus 47.8%). The side effect frequencies were comparable between the groups. CONCLUSION: Naproxen, adjunct to fluoxetine, outperformed adjunctive placebo in treating obsession and total symptoms of OCD patients in a safe and tolerable manner. CLINICAL TRIAL REGISTRATION: The study protocol was registered and published in the Iranian Registry of Clinical Trials (http://www.irct.ir; registration number IRCT20090117001556N139).

A rare occurrence of Vancomycin-induced gastrointestinal hemorrhage without thrombocytopenia: a case report and literature review.

BACKGROUND: Vancomycin-induced bleeding has been reported, attributed to the mechanism of immune thrombocytopenia. A rare case of vancomycin-induced gastrointestinal hemorrhage in a young patient with no underlying disease, receiving intravenous vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) infection, is presented. This occurrence occurred without thrombocytopenia. Relevant cases reported in the literature were also reviewed. CASE PRESENTATION: A 34-year-old male patient presented with maxillofacial multiple spaces infection accompanying left temporal abscess, bilateral lung abscesses. Culture results from both blood and secretion indicated that the infection was caused by MRSA. The patient received standard-dose vancomycin (1 g q12h intravenously guttae) for treatment. On the 5th day of therapy, he presented with bright red blood in his stool; however, vancomycin treatment was continued. By the 9th day, a decrease in hemoglobin level to 76 g/L and a platelet (PLT) count of 424 × 109/L raised concerns about gastrointestinal hemorrhage. The hemoglobin level decreased to 62 g/L on day 12. Due to the high tissue concentration of linezolid, administration of linezolid at a dose of 600 mg q12h intravenously guttae commenced on the 13th day as an alternative to vancomycin(D13-D17). Subsequently, on the 17th day, there was an improvement in hemoglobin level to 78 g/L. However, despite treatment with linezolid, the patient's fever showed no significant improvement, prompting a switch back to vancomycin at a dosage of 1 g q12h intravenously guttae(D18-D22). On the 21st day, there was a recurrence of gastrointestinal hemorrhage, accompanied by a hemoglobin level of 42 g/L and a PLT count of 224 × 109/L. Gastroscopy revealed the presence of a gastroduodenal ulcer. The patient had no prior history of hemorrhoids, gastrointestinal ulcers, liver cirrhosis, or purpura. Prior to admission, he had not been administered non-steroidal anti-inflammatory drugs (NSAIDs) or steroids. During hospitalization, the only medications given were vancomycin, ambroxol and lidocaine. Additional tests ruled out immunological disorders as the cause of gastrointestinal ulcers, and a positive vancomycin rechallenge test indicated an association between vancomycin and bleeding. After discontinuation of vancomycin, no further bleeding occurred. This case highlights a rare occurrence of vancomycin-induced bleeding without thrombocytopenia, classified as "Certain" according to the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale for standardized case causality assessment. CONCLUSION: This case represents the first documented instance of vancomycin-induced bleeding without thrombocytopenia, as confirmed by a positive rechallenge test. This discovery will aid in the early detection of this rare adverse reaction in future cases.

Leflunomide induced fatal dress syndrome need liver transplantation.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe, potentially life-threatening, drug-induced hypersensitivity reaction that involves hematological abnormalities (atypical lymphocytosis, eosinophilia), lymphadenopathy, skin eruption, and internal organ involvement (lung, liver, kidney). The 36-year-old female patient was followed by bloody diarrhea, diffuse skin rashes and hepatitis. She was diagnosed with psoriatic arthritis, and Leflunomide 20 mg was added to the treatment six weeks ago. Upon developing hepatic encephalopathy and deepening the fulminant liver failure during the follow-up, a living donor liver from her son was transplanted on the 4th day of hospitalization. The patient had deceased on the second day after liver transplantation due to multiple organ failures. In the literature, mortality in DRESS syndrome is mostly secondary to hepatic failure. Liver transplantation cannot be effective due to systemic involvement and recurrence in the transplanted liver.

Data-Driven Clinical Pharmacy Research: Utilizing Machine Learning and Medical Big Data.

To conduct clinical pharmacy research, we often face the limitations of conventional statistical methods and single-center observational study. To overcome these issues, we have conducted data-driven research using machine learning methods and medical big data. Decision tree analysis, one of the typical machine learning methods, has a flowchart-like structure that allows users to easily and quantitatively evaluate the occurrence percentage of events due to the combination of multiple factors by answering related questions with Yes or No. Using this feature, we first developed a risk prediction model for acute kidney injury caused by vancomycin, a condition we frequently encounter in clinical practice. Additionally, by replacing the prediction target from a binary variable (i.e., presence or absence of adverse drug reactions) to a continuous variable (i.e., drug dosage), we built a model to estimate the initial dose of vancomycin required to reach the optimal blood level recommended by guidelines. We found its accuracy to be better than that of conventional dose-setting algorithms. Moreover, employing Japanese medical big data such as the claims database helped us overcome the major limitations of conventional clinical pharmacy research such as institutional bias caused by single-center studies. We demonstrated that the combined use of machine learning and medical big data could generate high-quality evidence leveraging the strengths of each approach. Data-driven clinical pharmacy research using machine learning and medical big data has enabled researchers to surpass the limitations of conventional research and produce clinically valuable findings.

[Frequency of cutaneous drug reactions in the outpatient dermatology clinic at the National Institute of Cardiology Ignacio Chávez over a ten-year period]. / Frecuencia de reacciones adversas cutáneas a medicamentos en la consulta externa de dermatología del Instituto Nacional de Cardiología Ignacio Chávez, en un periodo de diez años.

Cutaneous adverse drug reactions, or pharmacodermias, are the most common form of adverse drug reactions (ADR). It was our interest to know their epidemiological behavior in a tertiary hospital level in Mexico. We stablished the frequency of ADR in 61 infants and adults hospitalized patients and those seen in the outpatient Dermatology Clinic at the National Institute of Cardiology Ignacio Chávez in Mexico City (INCICh) over a period of 10 years. The most frequently diagnosed pharmacodermias were acneiform dermatitis, cutaneous hyperpigmentation and maculopapular exanthema mainly associated to prednisone, hydroxychloroquine, cephalothin, amiodarone and vitamin B-complex, although we registered less frequently more severe and hazardous reactions. These results were consistent with other reports in our country. Multiple drugs administered at a time was an important causative factor for the ADR. It is necessary for every practitioner to develop skills that permit the identification of these dermatoses in order to correctly manage each case and diminish the morbimortality associated.

Las reacciones adversas cutáneas a medicamentos o farmacodermias constituyen la forma más común de las reacciones adversas a medicamentos (RAM), por lo que fue nuestro interés conocer su comportamiento epidemiológico en un hospital de tercer nivel en México. Establecimos su frecuencia en 61 pacientes, infantes y adultos, hospitalizados y de la Consulta externa de Dermatología en el Instituto Nacional de Cardiología Ignacio Chávez (INCICh) en la Ciudad de México, en 10 años, y encontramos que la reacciones más frecuentes fueron la dermatitis acneiforme, la hiperpigmentación cutánea y el exantema maculopapular principalmente asociados a prednisona, hidroxicloroquina, cefalotina, amiodarona y complejo B, aunque con menos frecuencia registramos reacciones más graves, lo cual es consistente con otros reportes similares en nuestro país. La polifarmacia de la mayoría de los pacientes que presentaron estas RAM fue un factor determinante en su presentación. Es fundamental desarrollar habilidades para reconocer el cuadro clínico de estas dermatosis, con el fin de abordar correctamente cada caso y disminuir la morbimortalidad de las RAM.

The Use of Proton Pump Inhibitors in Patients with Liver Cirrhosis: Real Life Experience.

(1) Background: Proton pump inhibitors (PPIs) are commonly prescribed for gastric disorders. In patients with liver cirrhosis, PPI use is associated with an increased risk of spontaneous bacterial peritonitis and increased mortality rates; therefore, they should be used with caution. This study aims to evaluate the appropriateness of PPI prescriptions in hospitalized cirrhotic patients against current clinical guidelines to identify patterns of misuse and guide better prescribing practices. (2) Methods: A retrospective study was conducted on liver cirrhosis inpatients in an internal medicine department from January 2022 to May 2023. The primary measure was the proportion of PPI prescriptions aligned with clinical guidelines. Medical files were entirely reviewed by researchers to assess the appropriateness of PPI prescriptions using the current guidelines. Outcomes included the identification of common reasons for PPI prescription and the rate of inappropriate PPI use among the study population. (3) Results: The study included 189 cirrhotic patients, with PPIs prescribed to 95 (50.2%) patients during hospitalization and 75 (39.7%) patients at discharge. Among those, 47.4% of the inpatients and 34.7% at discharge had no valid indication for PPI administration. The most common reason for PPI prescription during hospital stays was gastritis, followed by antiplatelet use in high-risk patients, ulcers, and upper gastrointestinal bleeding. The most common inappropriate indication was portal hypertensive gastropathy (PHG), followed by treatment with corticosteroids and anticoagulants alone. We did not find an association between PPI administration during hospital stays and infections. Only in 4% of cases patients should have received PPIs and did not. (4) Conclusions: There is a concerning overprescription of PPIs in cirrhotic patients, often deviating from established guidelines. It subjects patients to unnecessary risks. There is an urgent need for increased awareness and adherence to clinical guidelines regarding PPI prescriptions in cirrhotic patients.

Safety Profile of Mass Administration of Albendazole Among School Children (6-19 Years): A Prospective Active Surveillance Study.

BACKGROUND: Infections with Soil-transmitted Helminths (STHs) impact about 24% of the global population. A disproportionate number of individuals, particularly those from low socioeconomic backgrounds, live in emerging nations. In India, between the ages of one and fourteen, almost 220 million children are susceptible to intestinal worm infestations caused by parasites. The National Deworming Day (NDD) initiative was started by the Indian government in February 2015 as a part of the National Health Mission to address this problem. Though the adverse effects of albendazole in routine therapy are known, the mass administration of the medicine in children as part of a public health program has not been adequately studied. OBJECTIVE: This study aimed to determine the occurrence, type, and severity of adverse drug reactions resulting from mass administration of albendazole in school children aged 6-19 years in a district of northern India. METHODS: Twenty specified clusters were randomly chosen from a total of 96 clusters in the district to participate in this prospective, descriptive, observational study that was carried out in Karnal, Haryana. Both a passive approach and an active adverse drug reaction reporting system were used in the study. The six-step process known as Deb's Active Surveillance & Assisted Reporting System was employed in our study. Adverse drug reactions were recorded using the suspected Adverse Drug Reaction (ADR) reporting form of the Pharmacovigilance Programme of India (PvPI). RESULTS: Twenty clusters with a combined total of 94 schools and 12,751 students were observed during the study. In this study, there were more female participants (N = 8,060; 63.21%) than male participants (N = 4,691; 36.78%). A total of 29 ADRs were reported. All reported ADRs were mild in nature. It was discovered that there were 1.37 incidences for every 1000 individuals. As illustrated in Fig. (1), the most frequently reported Adverse Drug Reactions (ADRs) were vomiting (N = 10), nausea (N = 4), abdominal pain (N = 2), and headache (N = 1). The majority of ADRs were categorized as probable (N=18; 62.06%), followed by possible (N=11; 37.93%). CONCLUSION: An active surveillance system alongside voluntary passive reporting during the mass administration of medicines can help evaluate the safety profile of the medicinal products. The occurrence of ADRs following mass administration of albendazole in school children was found to be only 1.37 incidences for every 1000 recipients, being mild in nature, with vomiting being the most common.

Rheumatic adverse events associated with biologic therapy for chronic rhinosinusitis: A systematic review and meta-analysis.

BACKGROUND: Biologic therapies approved for treating chronic rhinosinusitis with nasal polyps (CRSwNP) have well-established safety profiles but reports of rheumatic adverse events (AEs) are increasing and not well defined. This review aims to assess the risk and incidence of rheumatic AEs associated with biologic therapy in CRSwNP and summarize current reported management strategies. METHODS: A protocol was registered in PROSPERO [CRD42024525663]. A search was conducted in four electronic databases: Medline (Ovid), Embase, Scopus, and Cochrane CENTRAL from inception until January 4, 2024. Two reviewers independently screened citations and extracted data. Methodological quality was assessed using the Joanna Briggs Institute's critical appraisal tool. Data were pooled using a random effects model to calculate overall incidence and relative risk. RESULTS: Twenty-one studies met the final inclusion criteria, totaling 3434 patients of which 2763 (80%) received either dupilumab (n = 2257; 82%), mepolizumab (n = 372; 13%), or omalizumab (n = 134; 5%) for treatment of CRSwNP. The overall incidence rate for any on-treatment rheumatic AE was 0.05 per person-year (95% CI, 0.03-0.09, I2 = 75%). Biologic therapy increased the risk of developing a rheumatic AE (RR = 2.53; 95% CI, 1.29-4.94) compared with placebo. The most frequently reported rheumatic AE was arthralgia or joint pain (n = 94; 95%), followed by lupus-like syndrome or lupus erythematosus-like reaction (n = 2; 2.5%). Discontinuation of treatment was the most common intervention (n = 21, 39%). CONCLUSION: Biologic therapy increases the risk of rheumatic AEs in CRSwNP patients by over twofold. Healthcare providers should remain vigilant in monitoring rheumatic AEs and apply appropriate management strategies on a case-by-case basis.

Dihydropyrimidine Dehydrogenase Polymorphism c.2194G>A Screening Is a Useful Tool for Decreasing Gastrointestinal and Hematological Adverse Drug Reaction Risk in Fluoropyrimidine-Treated Patients.

Although the risk of fluoropyrimidine toxicity may be decreased by identifying poor metabolizers with a preemptive dihydropyrimidine dehydrogenase (DPYD) test, following international standards, many patients with wild-type (WT) genotypes for classic variations may still exhibit adverse drug reactions (ADRs). Therefore, the safety of fluoropyrimidine therapy could be improved by identifying new DPYD polymorphisms associated with ADRs. This study was carried out to assess whether testing for the underestimated c.2194G>A (DPYD*6 polymorphism, rs1801160) is useful, in addition to other well-known variants, in reducing the risk of ADRs in patients undergoing chemotherapy treatment. This retrospective study included 132 patients treated with fluoropyrimidine-containing regimens who experienced ADRs such as gastrointestinal, dermatological, hematological, and neurological. All subjects were screened for DPYD variants DPYD2A (IVS14+1G>A, c.1905+1G>A, rs3918290), DPYD13 (c.1679T>G, rs55886062), c.2846A>T (rs67376798), c.1236G>A (rs56038477), and c.2194G>A by real-time polymerase chain reaction (RT-PCR). In this cohort, the heterozygous c.2194G>A variant was present in 26 patients, while 106 individuals were WT; both subgroups were compared for the incidence of ADRs. This assessment revealed a high incidence of gastrointestinal and hematological ADRs in DPYD6 carriers compared to WT. Moreover, we have shown a higher prevalence of ADRs in females compared to males when stratifying c.2194G>A carrier individuals. Considering that c.2194G>A was linked to clinically relevant ADRs, we suggest that this variant should also be assessed preventively to reduce the risk of fluoropyrimidine-related ADRs.

Case series on monoclonal antibodies targeting calcitonin gene-related peptide in migraine patients during pregnancy: Enhancing safety data.

BACKGROUND: Monoclonal antibodies targeting calcitonin gene-related peptide (CGRP-mAbs) are approved for adult migraine prevention but pose safety concerns in pregnancy. We assess the safety of CGRP-mAbs in the periconceptional period through a case series and literature review. METHODS: Six migraine-diagnosed women received CGRP-mAbs; treatment ceased upon pregnancy. We collected data and conducted safety assessments. To provide a comprehensive context, we performed a literature review. RESULTS: The series includes three erenumab, two fremanezumab and one galcanezumab case. A fremanezumab recipient experienced miscarriage; severe perinatal asphyxia linked to dystocia occurred with erenumab (140 mg). Database reviews revealed 63 spontaneous abortions, eight premature births, and seven birth defects among 286 World Health Organization and 65 European Medicines Agency cases. These rates align with untreated population rates. CONCLUSIONS: CGRP-mAbs use in the periconceptional period does not lead to clinically significant increase in pregnancy-related pathology or adverse effects on newborns within our case series and the literature reviewed.

Improvement in Adverse Drug Reaction (ADR) Knowledge: A Pre- and Post-video Intervention Study Among Doctors.

Background Adverse drug reactions (ADRs) represent a significant public health concern, contributing to mortality, morbidity, and healthcare costs worldwide. Healthcare practitioners especially doctors play a vital role in identifying and reporting ADR. This study investigates the prevalence of knowledge regarding ADR among doctors and enhances it with educational intervention. It also explores the association between demographic factors and baseline ADR awareness. Methods A prospective cross-sectional interventional study was conducted among doctors in Ahmedabad, India, to evaluate their knowledge of ADR reporting and the effectiveness of an educational video intervention. Pre- and post-intervention questionnaires were administered to assess knowledge improvement. Statistical analysis, including paired t-tests and chi-square tests, was performed to evaluate the intervention's impact and explore associations between demographic factors and ADR awareness. Results Analysis of pre- and post-intervention questionnaires revealed a significant increase in correct response rates post-intervention, indicating the effectiveness of the educational video intervention. Demographic factors, particularly age, were associated with ADR awareness. Following the intervention, participants demonstrated an improved understanding of ADR definitions, WHO causality assessment, reporting mechanisms, and challenges faced by pharmacovigilance programs. All participants found the video helpful and expressed intent to share their knowledge post-intervention. Conclusion The results of the study suggest that educational video intervention can serve as an effective tool for understanding ADR concepts and pharmacovigilance practices. Moreover, the association of demographic factors, particularly age, with ADR awareness further emphasizes the importance of educational interventions in addressing specific population needs.

Ibrutinib-Related Uveitis in Non-Hodgkin Lymphoma Patients: A Case Report and Literature Review.

PURPOSE: To report two cases of ibrutinib-related uveitis and review the literature to date. METHODS: We report two cases of ibrutinib-related uveitis using CARE guidelines and review the cases reported in the literature. RESULTS: Case 1) A 55-year-old female with recurrent primary central nervous system lymphoma presented with bilateral decreased visual acuity, photophobia, and floaters that started one month after initiating oral treatment with ibrutinib. Chronic non-granulomatous bilateral anterior-intermediate uveitis with macular edema was identified. Secondary causes were ruled out, and a presumptive diagnosis of ibrutinib-related uveitis was made. Case 2) A 57-year-old female with Waldenström macroglobulinemia who was treated with ibrutinib for two years presented with bilateral blurred vision, photophobia, red eyes, and floaters. A diagnosis of non-granulomatous, noninfectious panuveitis with bilateral cystoid macular edema was made. Secondary causes were ruled out, and ibrutinib toxicity was the most likely cause. CONCLUSION: Ibrutinib-related uveitis is a novel and under-diagnosed clinical entity. The most frequent clinical presentation in the literature is bilateral, non-granulomatous, anterior, and intermediate uveitis. Macular edema is a frequent complication. Uveitis usually requires topical treatment and the suspension of ibrutinib. Switching to second-generation Bruton tyrosine kinase inhibitors is proposed as a potential therapeutic alternative.