UNASSIGNED: Lorlatinib displays marked systemic and intracranial efficacy against anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC). We aimed to establish the safety profile of lorlatinib based on the Food and Drug Administration Adverse Event Reporting System (FAERS).
UNASSIGNED: Reports from the FAERS between 2019 and 2023 were collected to conduct the disproportionality analysis. Reporting odds ratio (ROR) was employed to detect the potential adverse events (AEs) related to lorlatinib. The clinical characteristics, age and gender differences, time to onset of AEs were also investigated.
UNASSIGNED: A total of 2,941 AE reports were found to be associated with lorlatinib among the 8,818,870 AE reports obtained from the FAERS database. 167 lorlatinib-related AE signals were identified. The frequently reported AEs including hypercholesterolemia, oedema, and cognitive disorder were in line with those observed in clinical trials and drug instruction. However, AEs such as interstitial lung disease and AV block indicated in the drug label require further evaluation. More attention should be paid to the new potential unexpected AEs including pulmonary arterial hypertension and radiation necrosis. Furthermore, we examined the specific high-risk AEs of different ages and genders. In addition, majority of AEs occurred within the first 2 months after lorlatinib initiation with a median onset time of 51 days.
UNASSIGNED: Our study provides valuable insight into the post-marketing safety profile of lorlatinib, which can potentially benefit the rational and safe administration of lorlatinib in the clinic. Further prospective studies are needed to validate the associations between lorlatinib and the identified AEs.

UNASSIGNED: Lumateperone, a novel antipsychotic drug that was granted by the Food and Drug Administration (FDA) approval in December 2019, remains insufficiently explored for its adverse event profile. This study used the FDA Adverse Event Reporting System (FAERS) database to explore its potential safety issues.
UNASSIGNED: This study conducted a retrospective analysis of FAERS data from the fourth quarter of 2019 to the third quarter of 2023, extracting reports related to lumateperone. Disproportionality analysis using Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) algorithms was employed to detect signals of adverse events (AEs).
UNASSIGNED: Our research processed 4,777 pertinent AE disclosures related to lumateperone, unveiling 125 signals that satisfied both ROR and BCPNN evaluative benchmarks across 26 System Organ Classes (SOCs). Intriguingly, 108 of these signals were categorized as unanticipated, spotlighting notable psychiatric manifestations such as mania (ROR = 73.82, 95% CI = 57.09-95.46; IC = 6.16, IC025 = 4.49), and hypomania (ROR = 34.74, 95% CI = 15.54-77.64; IC = 5.10, IC025 = 3.43), alongside non-psychiatric phenomena like urinary retention (ROR = 3.59, 95% CI = 1.80-7.19; IC = 1.84, IC025 = 0.18) and serotonin syndrome (ROR = 8.69, 95% CI = 4.81-15.72; IC = 3.11, IC025 = 1.45).
UNASSIGNED: This research provides real-world safety data on lumateperone post-marketing and is an important supplement to the information from clinical trial studies. Healthcare professionals should be vigilant for the risk of a manic switch in patients with bipolar depression who are administered lumateperone. More epidemiological studies are needed in the future to explore and further evaluate the risk-benefit issue of lumateperone.

To our knowledge, no prior study has analysed a possible association between acetazolamide and pulmonary oedema. The aim of this study was to use data from the EudraVigilance to detect a safety signal for acetazolamide-induced pulmonary oedema. We performed a disproportionality analysis (case-noncase method), calculating reporting odds ratios (RORs) up to 22 February 2024. Among 11 684 208 spontaneous cases of adverse reactions registered in EudraVigilance, 38 275 were pulmonary oedemas. Acetazolamide was involved in 31 cases. In more than half of those cases, the patients received a single dose of acetazolamide after undergoing cataract surgery: latency was 10-90 min. Remarkably, there were five cases of positive rechallenge and six cases resulted in death. The ROR for acetazolamide was 3.63 (95% CI 2.55-5.17). Disproportionality was also observed in VigiBase®: ROR 4.44 (95% CI 3.34-5.90). Our study confirms a signal that suggests a risk of serious pulmonary oedema associated with acetazolamide.

UNASSIGNED: The current study aims to assess the performance of data mining techniques in detecting safety signals for adverse events following immunization (AEFI) using routinely obtained data in China. Four different methods for detecting vaccine safety signals were evaluated.
UNASSIGNED: The AEFI data from 2011 to 2015 was collected for our study. We analyzed the data using four different methods to detect signals: the proportional reporting ratio (PRR), reporting odds ratio (ROR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). Each method was evaluated at 1-3 thresholds for positivity. To assess the performance of these methods, we used the published signal rates as gold standards to determine the sensitivity and specificity.
UNASSIGNED: The number of identified signals varied from 602 for PRR1 (with a threshold of 1) to 127 for MGPS1. When considering the common reactions as the reference standard, the sensitivity ranged from 0.9% for MGPS1/2 to 38.2% for PRR1/2, and the specificity ranged from 85.2% for PRR1 and ROR1 to 96.7% for MGPS1. When considering the rare reactions as the reference standard, PRR1, PRR2, ROR1, ROR2, and BCPNN exhibited the highest sensitivity (73.3%), while MGPS1 exhibited the highest specificity (96.9%).
UNASSIGNED: For common reactions, the sensitivities were modest and the specificities were high. For rare reactions, both the sensitivities and specificities were high. Our study provides valuable insights into the selection of signal detection methods and thresholds for AEFI data in China.

OBJECTIVE: This study examined whether state-level racial disproportionality in homelessness is associated with racial disproportionality in overdose mortality.
METHODS: Counts of individuals experiencing homelessness (2015-2017; by state and racial/ethnic group) were obtained from the US Department of Housing and Urban Development; population estimates and counts of drug overdose deaths (2018-2021; by state and racial/ethnic group) were obtained from the National Center for Health Statistics. Homelessness and overdose mortality disproportionality scores were calculated to indicate the extent to which each racial group was over- or under- represented among those experiencing homelessness, or among overdose deaths, respectively (relative to each racial group\'s proportional share in the general population). For each racial group examined, ordinary least squares regression models with robust standard errors (SEs) examined associations between state-level disproportionality in homelessness and disproportionality in overdose mortality, adjusting for percent aged 18-64 and US Census Region, as well as disproportionality in educational attainment and unemployment.
RESULTS: State-level racial disproportionality in homelessness was significantly and positively associated with racial disproportionality in overdose mortality for Black (b = 0.16 [SE = 0.05]; p < .01), American Indian/Alaska Native (b = 0.71 [SE = 0.23]; p < .01), and Hispanic populations (b = 0.17 [SE = 0.05]; p < .01), in models adjusting for region and percent aged 18-64. The significant positive associations in these three populations persisted after adjusting for educational attainment disproportionality, yet the association was no longer significant in the Black population after adjusting for unemployment disproportionality.
CONCLUSIONS: States with the highest levels of racial/ethnic minority overrepresentation in homelessness generally also had relatively higher levels of racial/ethnic minority overrepresentation in overdose deaths.

BACKGROUND: Current evidence on the safety of calcitonin gene-related peptide antagonists (CGRP-A) in pregnancy for the treatment of both episodic and chronic migraine is scarce and does not yet provide definitive information. By querying VigiBase®, the World Health Organization global pharmacovigilance database, this study aimed to detect differences in the reporting frequency between CGRP-A and triptans in relation to pregnancy.
METHODS: Disproportionality analyses on de-duplicated safety reports collected in VigiBase® as of 31.05.2023 reporting exposure to CGRP-A in pregnancy with or without pregnancy outcomes. A Reporting Odds Ratio (ROR) with a 95% confidence interval (CI) was used as a measure of disproportionality and the threshold for the detection of a signal of disproportionate reporting was set with a 95% CI lower limit > 1.
RESULTS: Four hundred sixty-seven safety reports reported exposure to CGRP-A in pregnancy, mostly originating from the United States of America (360/467, 77%), more frequently reported by patients (225/467, 48%), who were mainly females (431/467, 92%), and more frequently reported exposure to CGRP-A during pregnancy (400/467, 86%). Compared to triptans, no signals of disproportionate reporting were detected with CGRP-A either for the overall reporting of pregnancy-related safety reports (ROR 0.91, 95% CI 0.78-1.06), for the reporting of pregnancy outcomes (maternal and/or foetal/neonatal, ROR 0.54, 95% CI 0.45-0.66), or for the reporting of foetal/neonatal outcomes (ROR 0.53, 95% CI 0.41-0.68).
CONCLUSIONS: This study showed that, to date, there are no signals of increased reporting with CGRP-A compared to triptans in relation to pregnancy in VigiBase®. Future pharmacovigilance studies are needed to confirm these findings.

Background: Mepolizumab has been approved by the FDA for add-on maintenance treatment of severe asthma with an eosinophilic phenotype. Real-world studies on mepolizumab-associated adverse events are limited. The present study aimed to explore mepolizumab-related adverse events based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: A disproportionality analysis was performed to assess the safety profile of mepolizumab based on the reports from the FAERS database between October 2015 and December 2022. Demographic information, the time to onset, the safety of long-term mepolizumab exposure as well as safety in pediatric patients were also investigated. Results: A total of 736 significant preferred terms (PTs) were identified among the 13,497 mepolizumab-associated adverse events (AEs) reports collected from the FAERS database. The frequently reported AEs including dyspnea, fatigue, and headache were in line with drug instruction and previous studies. Unexpected significant AEs such as cough, malaise, and chest discomfort were also identified. Most AEs occurred within the first month after mepolizumab initiation. Pneumonia and wheezing were frequently reported in patients with long-term mepolizumab exposure as well as in the pediatric population. Conclusion: Our results were consistent with the observations in previous clinical and real-world studies. New and unexpected AE signals of mepolizumab were also identified. Close attention should be paid to the long-term safety of mepolizumab as well as safety in the pediatric population. Prospective studies are required for optimal use of mepolizumab.

In this study, we identified the specific discipline decision situations (i.e., vulnerable decision points [VDPs]) that contribute most to racial discipline disparities from a sample of 2020 schools across the United States. We also examined how much VDPs contributed to overall discipline disparities and the extent to which there was similarity among the strongest VDPs within each school. Last, we directly compared the VDP that contributed most to disparities in each school to situations with the highest rates of office discipline referrals (ODRs) to identify the extent of agreement with overall school discipline patterns. We found the most common VDPs within schools to be subjective behaviors (e.g., defiance, disruption) in classrooms throughout the day, with ODRs for physical aggression contributing notably to disparities among the top 10 VDPs. The strongest single VDP accounted for an average of 17% of racial disparities across the school and the top three VDPs accounted for 37% of disparities. The strongest three VDPs within schools also were remarkably consistent across behavior and location. Finally, there was moderate agreement between situations with the most ODRs and those with the strongest racial disparities, with 63% of schools in the sample having VDPs identical to their situations with most ODRs. In the absence of prescriptive analysis of their own school data, the results of this study provide school leaders and intervention researchers with more precise, promising targets for intervention to increase educational equity.

Child maltreatment is associated with significant morbidity, and prevention is a public health priority. Given evidence of interpersonal and structural racism in child protective service assessment and response, equity must be prioritized for both acute interventions and preventive initiatives aimed at supporting children and their families. Clinicians who care for children are well positioned to support families, and the patient-centered medical home, in collaboration with community-based services, has unique potential as a locus for maltreatment prevention services. Clinicians can advocate for policies that support families and decrease the risk of child maltreatment.

Drug-associated kidney injury is related to longer hospitalization and increased risk of chronic kidney disease and mortality. However, there is currently a lack of large population studies on drug-associated kidney injury in children. This study aimed to study perform data mining to generate hypotheses on drugs, which may deserve to be assessed as per their potential risk of increasing kidney injury in children. We extracted and analyzed reports on drugs associated with kidney injury in children in the FDA Adverse Event Reporting System (FAERS). We conducted a disproportionality analysis using proportional reporting ratio (PRR) to evaluate the association between drugs and kidney injury in children. Meanwhile, comparisons were performed with drug labels to identify drugs that, despite not having kidney injury currently mentioned in their labels, may potentially be associated with risks of kidney injury in children. A total of 6347 children had drug-associated kidney injury in the FAERS database. The top five drugs with the highest PRR were gentamicin (PRR = 12.28, N = 157 cases, Chi-Squared = 1602.77), piperacillin-tazobactam (PRR = 9.77, N = 129 cases, Chi-Squared = 1003.24), amlodipine (PRR = 8.98, N = 271 cases, Chi-Squared = 1861.46), vancomycin (PRR = 8.91, N = 295 cases, Chi-Squared = 1998.64), and ceftriaxone (PRR = 8.00, N = 251 cases, Chi-Squared = 1494.02). According to drug labels, 9 drugs (9/30) were classified as potential nephrotoxins.
CONCLUSIONS: Approximately one-third of drugs associated with kidney injury in children do not list kidney injury as a side effect in their drug labels. Future studies are therefore warranted to evaluate whether these drugs are associated with such a risk.
BACKGROUND: • Nephrotoxic drugs are an increasingly common cause of acute kidney injury in hospitalized children. • Currently, no study has systematically combed drugs associated with kidney injury in children.
BACKGROUND: • Approximately a third of drugs showing signals for potential kidney injury in children in data mining do not mention this side effect in their drug labels. • This study provides data on drugs needing further study to determine whether they might increase the risk of kidney injury in children.