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.

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).

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.

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.

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.

[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.

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.

Safety assessment of sulfasalazine: a pharmacovigilance study based on FAERS database.

Background: Sulfasalazine is a widely used anti-inflammatory medication for treating autoimmune disorders such as ulcerative colitis (UC), Crohn's disease, and rheumatoid arthritis. However, its safety profile has not been systematically evaluated in real-world settings. By analyzing the FDA Adverse Event Reporting System (FAERS) database, we identified risk signals associated with adverse reactions to sulfasalazine, offering valuable insights for clinical decision-making and risk management. Methods: Reports of adverse events (AEs) associated with sulfasalazine, covering the period from Q1 2004 to Q4 2023, were extracted from the FAERS database. Detailed case information was aggregated to assess demographic characteristics. The associations between sulfasalazine and adverse events were evaluated using the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM). Results: We extracted 7,156 adverse event reports from the FAERS database where sulfasalazine was identified as the "Primary Suspect (PS)" drug. Using disproportionality analysis, we identified 101 preferred terms (PT) related to sulfasalazine across 24 organ systems. Notable adverse reactions consistent with the drug's labeling were observed, including Stevens-Johnson syndrome, agranulocytosis, eosinophilic pneumonia, and crystalluria. Additionally, novel positive signals not previously documented in the drug label were identified, including acute febrile neutrophilic dermatosis, aseptic meningitis, glomerulonephritis, and hepatosplenic T-cell lymphoma. Conclusion: Most of the adverse reaction findings in this study are consistent with previous clinical research, and we have also identified new potential AEs associated with sulfasalazine. These findings provide valuable insights for the safety monitoring and clinical application of sulfasalazine.

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.

Re-Exposure to Culprit Medication Following Adverse Drug Event Diagnosis in Canadian Emergency Department Patients: A Cohort Study.

PURPOSE: The magnitude of repeat exposures to culprit medications after hospital discharge is not well studied. We combined prospective cohort data with administrative health data to understand the frequency of repeat exposures to culprit medications after discharge and the risk factors for their occurrence. METHODS: This was a retrospective analysis of three prospective cohorts of patients who presented to the hospital with an adverse drug event in British Columbia, from 2008 to 2015 (n = 849). We linked prospectively identified adverse drug events to administrative data to examine patterns of redispensing of culprit medications. We used Cox regression to assess risk factors for re-exposure, and conducted subgroup analyses for essential vs. nonessential medications. RESULTS: Among 849 diagnosed adverse drug events, 45.2% had subsequent culprit medication redispensing within a year of hospital discharge. The factors associated with re-exposures included atrial fibrillation, adverse drug event type (e.g. adverse reaction), culprit medication type, and longer historical duration of medication use. CONCLUSIONS: Re-exposures to culprit medications occurred in almost half of the adverse drug events diagnosed in emergency departments. Many of these were appropriate re-exposures to essential medications for indications in which the risk of uncontrolled disease likely outweighed the risk of a repeat adverse event. More research is needed to understand re-exposures to nonessential medications or medications with safer alternatives.

Possible Terbinafine and/or Itraconazole Induced Vasculitis - A Case Study.

INTRODUCTION: It is essential to exclude other causes, such as autoimmune diseases and bacterial infections, before attributing cutaneous/systemic vasculitis to drug use. CASE STUDY: This report discusses the case of a young man who developed multi-organ failure and cutaneous vasculitis following the use of antifungal medications (terbinafine and itraconazole) for dermatophyte infections. Tests for autoimmune diseases and infections were negative. Given his drug history and a skin biopsy indicating leukocytoclastic vasculitis, it was inferred that the vasculitis was likely drug-induced. Despite treatment with steroids, intravenous immunoglobulins, and plasmapheresis, the patient did not survive, possibly due to delayed diagnosis and treatment. CONCLUSION: In community practice, Drug-induced Vasculitis (DIV) is frequently overlooked. When patients present with skin rash, fever, and multi-organ dysfunction, DIV should be considered, particularly in the context of recent drug use. Over-the-counter antifungals, like terbinafine or itraconazole, can cause DIV and may be fatal if not promptly diagnosed and treated.

Research Progresses and Applications of Knowledge Graph Embedding Technique in Chemistry.

A knowledge graph (KG) is a technique for modeling entities and their interrelations. Knowledge graph embedding (KGE) translates these entities and relationships into a continuous vector space to facilitate dense and efficient representations. In the domain of chemistry, applying KG and KGE techniques integrates heterogeneous chemical information into a coherent and user-friendly framework, enhances the representation of chemical data features, and is beneficial for downstream tasks, such as chemical property prediction. This paper begins with a comprehensive review of classical and contemporary KGE methodologies, including distance-based models, semantic matching models, and neural network-based approaches. We then catalogue the primary databases employed in chemistry and biochemistry that furnish the KGs with essential chemical data. Subsequently, we explore the latest applications of KG and KGE in chemistry, focusing on risk assessment, property prediction, and drug discovery. Finally, we discuss the current challenges to KG and KGE techniques and provide a perspective on their potential future developments.

From common to unreported: a real-world study of adverse events to duloxetine in the treatment of osteoarthritis.

BACKGROUND: In a review of drug guidelines published by the International Association for the Study of Osteoarthritis, it is recommended to support the conditional use of duloxetine in patients with osteoarthritis. However, there is a lack of comprehensive research on the adverse events of duloxetine for the treatment of osteoarthritis populations. RESEARCH DESIGN AND METHODS: We used the reporting odds ratio (ROR) to determine the strength of the adverse event signal. In addition, we investigated trends in the occurrence of adverse events using the Weibull shape parameter (WSP) test. RESULTS: The results showed that 50 and 14 adverse events were detected in both Asian and American populations. Four new adverse events, Mouth ulceration, femoral neck fracture, incontinence, long QT syndrome, were identified. There was a difference in the time of adverse event induction between the North American and Asian populations (p < 0.0001). The Weibull shape parameter (WSP) test showed that the incidence of AE decreased over time. CONCLUSION: Our study contributes to an in-depth understanding of the safety of duloxetine in the treatment of osteoarthritis.

Suspected poor-quality medicines in Kenya: a retrospective descriptive study of medicine quality-related complaints reports in Kenya's pharmacovigilance database.

Poor-quality, substandard and falsified, medicines pose a significant public health threat, particularly in low-middle-income countries. A retrospective study was performed on Kenya's Pharmacovigilance Electronic Reporting System (2014-2021) to characterize medicine quality-related complaints and identify associations using disproportionality analysis. A total of 2767 individual case safety reports were identified, categorized into medicines with quality defects (52.1%), suspected therapeutic failure (41.6%), and suspected adverse drug reactions (6.3%). Predominantly reported were antineoplastic agents (28.6%), antivirals (11.7%), and antibacterial agents (10.8%) potentially linked to non-adherence to good manufacturing practices, inappropriate usage and supply chain degradation. Notably, analgesics (8.2%), and medical devices (3.5%) notified had quality defects, predominantly from government health facilities (60.0%). Antineoplastic agents (20.2%) and antivirals (3.7%) were frequently reported from suspected therapeutic failures and suspected adverse drug reactions, respectively, across both private for-profit facilities (26.5%) and not-for-profit facilities (5.4%). Underreporting occurred in unlicensed health facilities (8.1%), due to unawareness and reporting challenges. Pharmacists (46.1%), and pharmaceutical technicians (11.7%) predominantly reported quality defects, while medical doctors (28.0%) reported suspected therapeutic failures. Orally administered generic medicines (76.9%) were commonly reported, with tablets (5.8%) identified as potential sources of suspected adverse drug reactions, while quality defects were notified from oral solutions, suspensions, and syrups (7.0%) and medical devices (3.9%). The COVID-19 pandemic correlated with reduced reporting possibly due to prioritization of health surveillance. This study provides valuable evidence to supporting the use of medicine quality-related complaints for proactive, targeted regulatory control of high-risk medicines on the market. This approach can be strengthened by employing standardized terminology to prioritize monitoring of commonly reported suspected poor-quality medicines for risk-based sampling and testing within the supply chain.

Euglycemic Diabetic Ketoacidosis, Recurrent Genital Abscess, and Proximal Renal Tubular Acidosis With Concurrent SGLT-2 Inhibitor: More Than an Association.

Sodium-glucose transport protein 2 (SGLT2) inhibitors are a class of antidiabetic medications that have tremendous benefits in diabetic patients through reducing renal tubular glucose reabsorption, therefore inducing a rapid increase in urinary glucose excretion, thus reducing the overall serum blood glucose. However, the medication's use has commonly been associated with emerging complications such as euglycemic diabetic ketoacidosis (eDKA), a rare and life-threatening metabolic disturbance. Other complications that have been associated with this class of medications are recurrent genital abscesses and renal tubular acidosis, which have both been less reported and explored. Below, we detail the case of a woman who was on empagliflozin, an SGLT2 inhibitor, for only two months and developed life-threatening eDKA, recurrent genital abscesses, and proximal renal tubular acidosis all within the two months of initiation of the medication.

Immune checkpoint blockade lowers the threshold of naïve T-cell priming to drug-associated antigens in a dose-dependent fashion.

A growing body of clinical and experimental evidence indicates that immune checkpoint blockade enhances patient susceptibility to hypersensitivity reactions to co-administered medications. In this study, we utilized an in vitro T-cell priming assay to demonstrate one of the mechanistic hypotheses on how this occurs; through lowering of the threshold in patients to elicit aberrant T-cell responses. We outline the dependency of de novo T-cell priming responses to drug-associated antigens on dose at initial exposure. Findings support the aforementioned hypothesis and offer an experimental representation of fundamental parameters at play in hypersensitivity reactions to low molecular weight compounds.