Evaluation of Antipsychotic-Induced Neuroleptic Malignant Syndrome Using a Self-Organizing Map.

Introduction In neuropsychiatric pharmacotherapy, neuroleptic malignant syndrome (NMS) is a potentially serious side effect of antipsychotics characterized primarily by fever, disorientation, extrapyramidal disorders, and autonomic nervous system imbalance, which can lead to death if left untreated. We visualized the NMS profile of antipsychotics using a self-organizing map (SOM). We combined it with decision tree analysis to discriminate between 31 antipsychotics in more detail than typical antipsychotic (TAP) and atypical antipsychotic (AAP) classifications. Method A total of 20 TAPs and 11 AAPs were analyzed. We analyzed NMS reports extracted from the Japanese Adverse Drug Event Report (JADER) database based on standardized Medical Dictionary for Regulatory Activities (MedDRA) queries (Standardized MedDRA Queries (SMQ) code: 20000044, including 68 preferred terms). The SOM was applied using the SOM package in R version 4.1.2 (R Foundation for Statistical Computing, Vienna, Austria). Results The Japanese Adverse Drug Event Report (JADER) database contained 887,704 reports published between April 2004 and March 2024. The numbers of cases of NMS (SMQ code: 20000044) reported for risperidone, aripiprazole, haloperidol, olanzapine, and quetiapine were 1691, 1294, 1132, 1056, and 986, respectively. After the antipsychotics were classified into six units using SOM, they were adapted for decision tree analysis. First, 31 antipsychotics branched off into groups with loss of consciousness, with one group (10 TAPs) consisting entirely of TAPs, and the other consisting of antipsychotics that were further separated into two groups with coma induced by TAPs and AAPs. Conclusion The results of this study provide a reference for healthcare providers when predicting the NMS characteristics induced by each drug in patients, thereby facilitating the effective treatment of schizophrenia.

A study on user willingness to participate in an adverse drug event information sharing system.

BACKGROUND: To prevent the recurrence of Adverse Drug Events (ADEs), particularly drug allergies, it is essential to avoid re-exposure to causative drugs. Awareness of previous ADEs is crucial for patients because they can share accurate information with healthcare providers (HCPs). This study aims to assess users' willingness to share ADE information and evaluate the factors related to this willingness by utilizing a prospective ADE information-sharing system currently under consideration in South Korea. METHODS: In September 2023, a self-administered questionnaire was collected from a sex-, age-, and regionally stratified nationwide convenience sample of adults recruited through a commercial panel in South Korea. Factors contributing to the willingness to share ADE information and create electronic ADE cards (e-ADE cards) were investigated using multivariate logistic regression analysis. RESULTS: Among the 1,000 respondents, 458 (45.8%) were willing to share ADE information, and 521 (52.1%) were willing to create e-ADE cards. The willingness to share personal ADE information and create e-ADE cards was positively associated with the perceived benefits of sharing ADE, trust in HCPs and positive experiences. Notably, older adult patients demonstrated a higher willingness to share information and use e-ADE cards, with rates of 56% and 62%, respectively. CONCLUSIONS: Our findings indicate that the approach to sharing personal ADE information should be distinct from that of sharing comprehensive health information. Notably, users are likely to willingly disclose their personal information even if they are not anonymized, owing to the significant perceived benefits of sharing. The findings of this study can enhance awareness about sharing personal ADE information and contribute to the successful establishment of an ADE information-sharing system, thereby improving the patient safety environment.

Disproportionality analysis of flutamide- or bicalutamide-induced liver injury with and without steroids by using the Japanese Adverse Drug Event Report database.

BACKGROUND: Although the mechanism underlying flutamide- or bicalutamide-induced liver injury may be immune related, the details remain unclear. If this mechanism is immune related, steroid use may be considered as a treatment option. AIM: Disproportionality analysis was conducted to evaluate the effect of concomitant steroid use on flutamide- and bicalutamide-induced liver injury. METHOD: Male patients aged 20 years or older who were receiving nonsteroidal anti-androgens from April 2004 to October 2023 were screened from the Japanese Adverse Drug Event Report database. Data on liver injury, age, weight, height, steroid use, obesity, hepatic stenosis, alcohol-related hepatic disorders, hepatitis B and C, and common drugs known to cause drug-induced liver injury were analyzed. Liver injury was defined by the Standardized Medical Dictionary for Regulatory Activities query index (code 20000006, version 27.0). RESULTS: Among 142,430 patients, 2,316 were administered nonsteroidal anti-androgens. Reports of liver injury were disproportionate depending on the agents used (reporting odds ratio [ROR], 1.29; 95% confidence intervals [CI], 1.13-1.46), especially among flutamide or bicalutamide users (flutamide: ROR, 6.09; 95% CI, 4.51-8.23; bicalutamide: ROR, 1.24; 95% CI, 1.05-1.48). Multivariable logistic regression analysis correlated steroid use with a lower risk of flutamide- or bicalutamide-induced liver injury (flutamide: odds ratio, 0.07; 95% CI, 0.01-0.52; bicalutamide: odds ratio, 0.45; 95% CI, 0.21-0.96). CONCLUSION: Our findings suggest that flutamide and bicalutamide may increase the risk of liver injury compared to enzalutamide, apalutamide, and darolutamide. Furthermore, our study indicated that steroid use could aid in the management of liver injury.

Intravenous iron staining. Real-world incidence, preventability, and mitigation tools from a long-term quality improvement project.

BACKGROUND: Iron deficiency is the leading cause of anaemia worldwide and is increasingly treated with intravenous iron therapy. Staining from intravenous iron therapy is a rare but significant and preventable adverse event. To mitigate patient harm, a health service wide quality improvement project was implemented. This study aimed to determine the real-world impact of a quality improvement project on intravenous staining incidents and preventability. METHODS: A retrospective chart audit was undertaken for all intravenous iron staining episodes reported in a directorate-wide clinical incident reporting database (RiskMan) between 2016 and 2022. Incidence rates of intravenous iron staining, preventability and stain severity were compared pre and post implementation of a standardised intravenous iron procedure. RESULTS: Over seven years, 103 intravenous iron stains were identified, resulting in a staining rate of 0.31 stains per 100 infusions (pre 0.27% and post 0.34%, p=0.25). Implementation of the standardised intravenous iron procedure resulted in improvements in pharmacist review of the medication order (61.8% V 89.7%, p<0.01), use of the statewide IV iron infusion consent form (27.3% V 76.9%, p<0.01) and appropriate cannula site (14.3% V 52.5%, P<0.01). Smaller stain sizes were associated with cessation of the infusion at identification of extravasation (312cm2 V 35cm2) (p = 0.04). Preventability was assigned to 86% of stains. CONCLUSION: The incidence rate of intravenous iron staining in a real-world clinical setting is 0.31%. There was increased compliance with several best practice principles and 86% of stains were preventable. Early identification and intervention of potential staining incidents results in smaller iron stains for patients. Quality improvement tools developed for this project can contribute to patient outcomes internationally.

High Burden of Ileus and Pneumonia in Clozapine-Treated Individuals With Schizophrenia: A Finnish 25-Year Follow-Up Register Study.

OBJECTIVE: The authors used longitudinal biobank data with up to 25 years of follow-up on over 2,600 clozapine users to derive reliable estimates of the real-world burden of clozapine adverse drug events (ADEs). METHODS: A total of 2,659 participants in the FinnGen biobank project had a schizophrenia diagnosis and clozapine purchases with longitudinal electronic health record follow-up for up to 25 years after clozapine initiation. Diseases and health-related events enriched during clozapine use were identified, adjusting for disease severity. The incidence and recurrence of ADEs over years of clozapine use, their effect on clozapine discontinuation and deaths, and their pharmacogenetics were studied. RESULTS: Median follow-up time after clozapine initiation was 12.7 years. Across 2,157 diseases and health-related events, 27 were enriched during clozapine use, falling into five disease categories: gastrointestinal hypomotility, seizures, pneumonia, other acute respiratory tract infections, and tachycardia, along with a heterogeneous group including neutropenia and type 2 diabetes, among others. Cumulative incidence estimates for ileus (severe gastrointestinal hypomotility) and pneumonia were 5.3% and 29.5%, respectively, 20 years after clozapine initiation. Both events were significantly associated with increased mortality among clozapine users (ileus: odds ratio=4.5; pneumonia: odds ratio=2.8). Decreased genotype-predicted CYP2C19 and CYP1A2 activities were associated with higher pneumonia risk. CONCLUSIONS: Clozapine-induced ileus and pneumonia were notably more frequent than has previously been reported and were associated with increased mortality. Two CYP genes influenced pneumonia risk. Pneumonia and ileus call for improved utilization of available preventive measures.

High-risks drug adverse events associated with Cetirizine and Loratadine for the treatment of allergic diseases: A retrospective pharmacovigilance study based on the FDA adverse event reporting system database.

BACKGROUND: Cetirizine and Loratadine are the two best-selling second-generation antihistamines for allergic diseases. This study aims to provide a comparative analysis of the differences in adverse drug events (ADEs) between these two medications, which can assist clinicians in making appropriate treatment decisions. METHODS: ADE reports related to Cetirizine and Loratadine obtained from the FDA adverse event reporting system (FAERS) database were analyzed using disproportionality analysis and Bayesian analysis to evaluate and compare the ADE signals of both drugs. RESULTS: A total of 28,051 and 28,073 ADE reports were retrieved from the FAERS database related to Cetirizine and Loratadine, respectively, with both drugs showing a predominance of middle-aged females. Specifically, Loratadine was associated with respiratory symptoms, mainly nasal symptoms such as rhinorrhea (n = 326, ROR 6.75), sneezing (n = 251, ROR 15.24), and nasal congestion (n = 185, ROR 4.25), while Cetirizine did not show this association. Notably, both drugs exhibited strong signals for somnolence in the nervous and psychiatric systems, especially Cetirizine (Cetirizine, n = 2556, ROR 10.52 vs. Loratadine, n = 1200, ROR 7.76). Additionally, Cetirizine itself showed strong signals for attention disturbance (n = 233, ROR 3.3), while Loratadine was associated with nervousness (n = 145, ROR 3.3). Further exploration revealed more severe adverse reactions closely associated with Cetirizine, including hallucinations, aggression, and abnormal behavior. Importantly, Cetirizine was significantly associated with the occurrence of pericarditis (n = 138, ROR 8.13), potentially leading to serious adverse consequences. CONCLUSION: Compared to Loratadine, Cetirizine poses a greater potential risk in the nervous and psychiatric systems. Additionally, this study reveals previously underestimated potential cardiac toxicity of Cetirizine; albeit at a relatively low incidence rate, the high signal intensity warrants further attention and exploration. These findings highlight the need for enhanced patient monitoring and therapy optimization when prescribing these medications, ensuring better management of allergic diseases while minimizing risks.

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.

Developing large language models to detect adverse drug events in posts on x.

Adverse drug events (ADEs) are one of the major causes of hospital admissions and are associated with increased morbidity and mortality. Post-marketing ADE identification is one of the most important phases of drug safety surveillance. Traditionally, data sources for post-marketing surveillance mainly come from spontaneous reporting system such as the Food and Drug Administration Adverse Event Reporting System (FAERS). Social media data such as posts on X (formerly Twitter) contain rich patient and medication information and could potentially accelerate drug surveillance research. However, ADE information in social media data is usually locked in the text, making it difficult to be employed by traditional statistical approaches. In recent years, large language models (LLMs) have shown promise in many natural language processing tasks. In this study, we developed several LLMs to perform ADE classification on X data. We fine-tuned various LLMs including BERT-base, Bio_ClinicalBERT, RoBERTa, and RoBERTa-large. We also experimented ChatGPT few-shot prompting and ChatGPT fine-tuned on the whole training data. We then evaluated the model performance based on sensitivity, specificity, negative predictive value, positive predictive value, accuracy, F1-measure, and area under the ROC curve. Our results showed that RoBERTa-large achieved the best F1-measure (0.8) among all models followed by ChatGPT fine-tuned model with F1-measure of 0.75. Our feature importance analysis based on 1200 random samples and RoBERTa-Large showed the most important features are as follows: "withdrawals"/"withdrawal", "dry", "dealing", "mouth", and "paralysis". The good model performance and clinically relevant features show the potential of LLMs in augmenting ADE detection for post-marketing drug safety surveillance.

Disproportionality analysis of cardiac adverse events associated with lenvatinib using the Japanese Adverse Drug Event Report database.

AIMS: This study was conducted to examine disproportionality, times to onset, incidence rates and outcomes of lenvatinib-associated cardiac adverse events (AEs) using the Japanese Adverse Drug Event Report database. METHODS: We analysed data for the period between April 2004 and May 2023. Data on cardiac AEs were extracted and the relative disproportionality of AEs was estimated using reporting odds ratios (RORs). Furthermore, Weibull distribution parameters were calculated. RESULTS: Of the 2 230 863 reports analysed, we identified 7684 reports of AEs associated with lenvatinib, including 317 cardiac AEs. Signals were detected for eight cardiac AEs: hypertension, cardiac failure, myocarditis, myocardial infarction, immune-mediated myocarditis, cardiomyopathy, angina unstable and cardiotoxicity. Among these, fatal outcomes were observed for cardiac failure, myocarditis and myocardial infarction. Histograms of median times to onset for the eight detected cardiac AE signals showed that AEs occurred at a median of 3.5-134.5 days after lenvatinib administration. The Weibull distributions showed that cardiac failure occurred early after administration (early failure type), myocarditis occurred in a dose-dependent manner (wearout failure type), and myocardial infarction occurred constantly throughout the exposure period (random failure type). CONCLUSIONS: We focused on cardiac AEs associated with lenvatinib as post-marketing AEs. Serious outcomes can arise after lenvatinib administration. Patients should be monitored for signs of onset of these AEs not only at the start of administration, but also over an extended period.

Disproportionality Analysis of Osimertinib-related Adverse Events in Elderly Patients Using the Japanese Pharmacovigilance Database.

Background/Aim: Osimertinib is a well-tolerated first- or second-line treatment option for elderly patients with epidermal growth factor receptor mutation-positive advanced non-small cell lung cancer. However, the safety of osimertinib in elderly patients requires further investigation. Herein, we identified safety signals for various osimertinib-related adverse events (AEs) in elderly patients by disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. Patients and Methods: Data from the JADER database from April 2004 to March 2023 were obtained from the Pharmaceuticals and Medical Devices Agency website. Safety signal detection for osimertinib-related AEs in elderly patients (≥70 years old) was determined using the relative elderly reporting odds ratio (ROR). For osimertinib-related AEs, we extracted 92 preferred terms (PTs) and nine standardized MedDRA queries (SMQs). Results: Safety signals in elderly patients were detected for "Cardiomyopathy (PT)" and "Cardiomyopathy (SMQ)". The symptoms most frequently associated with "Cardiomyopathy (SMQ)" included "Ejection fraction decreased (PT)", "Cardiomyopathy (PT)", and "Stress cardiomyopathy (PT)". Notably, 53.7% of these outcomes were "Recovery" or "Remission". The median time to the onset of "Cardiomyopathy (SMQ)" in elderly patients was 85 days (range=2-537 days). Conclusion: We demonstrated that patients ≥70 years potentially have increased osimertinib-related cardiomyopathy compared with patients <70 years. In the future, it is necessary to conduct research focusing on cardiomyopathy in elderly patients.

Assessment of drug-drug interactions among patients with hematologic malignancy: A clinical pharmacist-led study.

INTRODUCTION: Patients with hematologic malignancies often receive multiple medications, leading to potential drug-drug interactions (DDIs). Identifying and managing these DDIs is crucial for ensuring patient safety and effective care. This study aimed to identify and describe DDIs and associated factors in hematologic malignancy patients. METHODS: This prospective interventional study was conducted at a referral center and included hospitalized patients with hematologic malignancies who were receiving at least four concurrent medications. A pharmacist initially compiled a comprehensive list of all medications through patient interviews and medication reviews, and subsequently, identified and categorized potential DDIs using the Lexi-interact® and Micromedex® databases. The clinical pharmacist then evaluated the clinical impact of the identified DDIs in every individual patient and provided appropriate interventions to resolve them. RESULTS: A total of 200 patients met the inclusion criteria for the study, with 1281 DDIs identified across 337 distinct types. The majority of identified DDIs exhibited major severity (52.1%) and pharmacokinetic mechanisms (50.3%), with an unspecified onset (79.4%) and fair evidence (67%). Of the identified DDIs, 81.1% were considered clinically significant, prompting 1059 pharmacotherapy interventions by the clinical pharmacist. Additionally, a significant relationship was observed between the number of drugs used during hospitalization and the occurrence of DDIs (P < 0.001, r = 0.633). CONCLUSION: DDIs are highly prevalent among hospitalized patients with hematologic malignancies, with their occurrence increasing alongside the number of medications administrated. The intervention of a clinical pharmacist is crucial to evaluate the clinical impact of these DDIs and implement effective interventions for their management.

Analysis of anticholinergic drugs associated with aspiration pneumonia using the Japanese adverse drug event report database: Supplementary insights from a scoping review.

BACKGROUND: Japan's super-aged society presents significant challenges, particularly with regard to managing aspiration pneumonia among older adults. We aimed to investigate the link between anticholinergic drug use and the incidence of aspiration pneumonia, primarily utilizing data from the Japanese Adverse Drug Event Report (JADER) database. METHODS: The primarily analysis included JADER data from the first quarter of 2004 through the third quarter of 2023, focusing on 2367 cases of aspiration pneumonia in individuals aged ≥60 years. The study examined the association of aspiration pneumonia with 49 drugs listed in the Anticholinergic Risk Scale, using the Reporting Odds Ratio for signal detection. A scoping review incorporating findings from MEDLINE and the Cochrane Library was conducted to validate these associations. RESULTS: The primary analysis identified an increased risk of aspiration pneumonia associated with specific drugs, including clozapine, haloperidol, risperidone, quetiapine, and olanzapine. A total of 20 drugs were significantly associated with an increased risk of aspiration pneumonia. Our results emphasize the importance of considering the dopamine-blocking effects of these drugs, particularly in at-risk populations, such as older adults, and those with conditions, such as schizophrenia or Parkinson's disease. CONCLUSIONS: The study highlights the importance of careful monitoring of anticholinergic drugs with potent dopamine-blocking effects, such as clozapine, haloperidol, risperidone, quetiapine, and olanzapine, to reduce the risk of aspiration pneumonia. Future research should include observational and interventional studies to further investigate these findings. ETHICS AND DISSEMINATION: As this study utilized pre-existing anonymized information, approval from an ethics committee was not required.

Inhaled analgesics for the treatment of prehospital acute pain-A systematic review.

BACKGROUND: Many prehospital emergency patients receive suboptimal treatment for their moderate to severe pain. Various factors may contribute. We aim to systematically review literature pertaining to prehospital emergency adult patients with acute pain and the pain-reducing effects, adverse events (AEs), and safety issues associated with inhaled analgetic agents compared with other prehospital analgesic agents. METHODS: As part of an initiative from the Scandinavian Society of Anaesthesia and Intensive Care Medicine, we conducted a systematic review (PROSPERO CRD42018114399), applying the PRISMA guidelines, Grading of Recommendations Assessment, Development, and Evaluation (GRADE), and Cochrane methods, searching the Cochrane Library, Epistemonikos, Centre for Reviews and Dissemination, PubMed, and EMBASE databases (updated March 2024). Inclusion criteria were the use of inhaled analgesic agents in adult patients with acute pain in the prehospital emergency care setting. All steps were performed by minimum of two individual researchers. The primary outcome was pain reduction; secondary outcomes were speed of onset, duration of effect, and relevant AEs. RESULTS: We included seven studies (56,535 patients in total) that compared inhaled agents (methoxyflurane [MF] and nitrous oxide [N2O]) to other drugs or placebo. Study designs were randomized controlled trial (1; n = 60), randomized non-blinded study (1; n = 343), and randomized open-label study (1; n = 270). The remaining were prospective or retrospective observational studies. The evidence according to GRADE was of low or very low quality. No combined meta-analysis was possible. N2O may reduce pain compared to placebo, but not compared to intravenous (IV) paracetamol, and may be less effective compared to morphine and MF. MF may reduce pain compared to paracetamol, ketoprofen, tramadol, and fentanyl. Both agents may be associated with marked but primarily mild AEs. CONCLUSION: We found low-quality evidence suggesting that both MF and N2O are safe and may have a role in the management of pain in the prehospital setting. There is low-quality evidence to support MF as a short-acting single analgesic or as a bridge to IV access and the administration of other analgesics. There may be occupational health issues regarding the prehospital use of N2O.

Interpretable machine learning model predicting immune checkpoint inhibitor-induced hypothyroidism: A retrospective cohort study.

Hypothyroidism is a known adverse event associated with the use of immune checkpoint inhibitors (ICIs) in cancer treatment. This study aimed to develop an interpretable machine learning (ML) model for individualized prediction of hypothyroidism in patients treated with ICIs. The retrospective cohort of patients treated with ICIs was from the First Affiliated Hospital of Ningbo University. ML methods applied include logistic regression (LR), random forest classifier (RFC), support vector machine (SVM), and extreme gradient boosting (XGBoost). The area under the receiver-operating characteristic curve (AUC) was the main evaluation metric used. Furthermore, the Shapley additive explanation (SHAP) was utilized to interpret the outcomes of the prediction model. A total of 458 patients were included in the study, with 59 patients (12.88%) observed to have developed hypothyroidism. Among the models utilized, XGBoost exhibited the highest predictive capability (AUC = 0.833). The Delong test and calibration curve indicated that XGBoost significantly outperformed the other models in prediction. The SHAP method revealed that thyroid-stimulating hormone (TSH) was the most influential predictor variable. The developed interpretable ML model holds potential for predicting the likelihood of hypothyroidism following ICI treatment in patients. ML technology offers new possibilities for predicting ICI-induced hypothyroidism, potentially providing more precise support for personalized treatment and risk management.

Initiating an Insulin Safety Campaign to reduce the incidence of glycemic harm events for hospitalized adults 65 and older.

BACKGROUND: During calendar years 2021 through 2023, our health system admitted 200,837 persons 18 years and older with diabetes, of which 61% (n = 123,393) were 65 years and older with orders for insulin administration. The incidence of diabetes among hospitalized persons 65 and older continues to increase in the United States, with 24 million adults 65 and older with diabetes reported in 2020. Insulin, a high-risk medication, has the potential for adverse drug events, which can cause significant harm to patients, potentially resulting in death. With the 2023 initiation of voluntary electronic clinical quality measures reporting for severe glycemic harm events from the Centers for Medicare Services, the study team saw an opportunity to evaluate and standardize insulin-related practices across the system. METHODS: We implemented an Insulin Safety Campaign (ISC), to review, evaluate, and standardize insulin-related processes across our health system. The primary goal was to reduce severe glycemic harm events system-wide. Insulin-related practices were reviewed for best practice alignment and standardized. Outcomes were measured according to the Centers for Medicare and Medicaid Services' electronic clinical quality measures reporting guidelines. RESULTS: Comparing pre-and post-implementation results, all five medical centers achieved statistically significant reductions in sever hyper- and hypoglycemic harm events. CONCLUSIONS: Through a collaborative effort, we were able to identify, address, and reduce insulin-related process variabilities through standardization, reducing the percentage of severe glycemic harm events and improving blood glucose management in our hospitalized persons 65 and older.

Unintended Consequences of Immune Therapy for Immune-Mediated Diseases: Paradoxical Psoriasis and Dupilumab-Associated Musculoskeletal Syndrome.

Two presentations at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting focused on unintended consequences of immunomodulatory therapy for psoriasis (PsO). Dr. Elizabeth Wallace presented on unintended consequences of tumor necrosis factor inhibitors for treating PsO and other inflammatory disorders. These consequences include paradoxical PsO, which is defined as unexpected new PsO cases or worsening PsO symptoms seemingly induced by treatment. Dr. Bruce Kirkham focused on unintended consequences of dupilumab treatment, which can include a musculoskeletal syndrome similar to psoriatic arthritis.

Pharmacology of emerging drugs for the treatment of multi-drug resistant tuberculosis.

Mycobacterium tuberculosis (TB) remains the leading cause of infection-related mortality worldwide. Drug resistance, need for multiple antimycobacterial agents, prolonged treatment courses, and medication-related side effects are complicating factors to TB cure. The introduction of treatment regimens containing the novel agents bedaquiline, pretomanid, and linezolid, with or without moxifloxacin (BPaL-M or BPaL, respectively) have substantially reduced TB-related morbidity and mortality and are associated with favorable rates of treatment completion and cure. This review summarizes key information on the pharmacology and treatment principles for moxifloxacin, bedaquiline, delamanid, pretomanid, linezolid, and tedizolid in the treatment of multi-drug resistant TB, with recommendations provided to address and attenuate common adverse effects during treatment.

Vonoprazan-associated Clostridioides difficile infection: an analysis of the Japanese Adverse Drug Event Report and the FDA Adverse Event Reporting System.

Background: Prolonged or excessive use of acid suppressants may increase the risk of Clostridioides difficile infection (CDI) by altering the intestinal microecosystem. Vonoprazan, a novel potassium-competitive acid blocker, exhibits a faster and more sustained acid-suppressive effect than proton pump inhibitors (PPIs). Therefore, vonoprazan may have a greater impact on the gut microbiota, potentially resulting in CDI. Objectives: This study aimed to explore the potential relationship between acid suppressants and CDI by the Japan Adverse Drug Event Report (JADER) and the FDA Adverse Event Reporting System (FAERS) databases. Design: A retrospective analysis of the JADER and FAERS databases was examined by disproportionality analysis. Methods: We performed signal detection analyses of CDI induced by vonoprazan and PPIs using the JADER and FAERS databases. The association between acid suppressants and CDI was calculated using the reporting odds ratio (ROR) and corresponding 95% confidence interval (95% CI). When the lower limit of the 95% CI is exceeded by 1, the association is considered statistically significant. Results: In the JADER database, the ROR (95% CI) for vonoprazan and PPIs based on suspect drug reports was 15.84 (12.23-20.50) and 2.51 (1.92-3.28), respectively. In the FAERS database, the ROR (95% CI) for vonoprazan and PPIs based on primary and secondary suspect drug reports was 11.50 (6.36-20.82) and 1.42 (1.34-1.51), respectively. Subgroup analysis showed that elderly patients aged 60 years and older were more strongly associated with CDI. The ROR (95% CI) for vonoprazan and PPIs in patients aged 60 years and older in the JADER database was 15.35 (11.59-20.33) and 1.65 (1.14-2.39), respectively. Similarly, the ROR (95% CI) for vonoprazan and PPIs in the FAERS database was 12.56 (6.26-25.20) and 1.43 (1.31-1.57), respectively. Excluding the effect of Helicobacter pylori (H. pylori) infection, the use of acid suppressants was still associated with CDI. Conclusion: While signal detection analysis based on the JADER and FAERS databases could not establish causality, our study demonstrated that both vonoprazan and PPIs were significantly associated with CDI. Vonoprazan showed a stronger association with CDI in both databases.

Introduction: Vonoprazan is a new type of acid suppressant, which has a stronger effect on acid inhibition than traditional proton pump inhibitors (PPIs). Vonoprazan may have a greater impact on the gut microbiota, which may increase the risk of Clostridioides difficile infection (CDI). The FDA created the FDA Adverse Event Reporting System (FAERS) database to support the post-market surveillance program. The PMDA created the Japan Adverse Drug Reaction Event Report (JADER) database to specifically collect adverse reaction reports in Japan. To further understand the potential relationship between acid suppressants and CDI, this study was analyzed using the JADER and FAERS databases. Methods: This study analyzed cases of CDI reported after the use of acid suppressants in the JADER and FAERS databases. Results: The analysis revealed that vonoprazan and PPIs are significantly associated with CDI in both databases. Notably, vonoprazan exhibited a stronger association compared to PPIs. Subgroup analysis indicated that this association was more pronounced in elderly patients aged 60 years and older. Additionally, excluding the influence of Helicobacter pylori (H. pylori) did not diminish the association between acid suppressants and CDI. Conclusion: Although signal detection analysis based on the JADER and FAERS databases could not establish causality, the results showed that both vonoprazan and PPIs were significantly associated with CDI. Vonoprazan was also more strongly associated with CDI than PPIs, which could be a potential safety concern, and further clinical studies are needed to confirm this finding.

Vonoprazan and Clostridioides difficile infection risk.