Triple challenges-small sample size in both exposure and control groups to scan rare maternal outcomes in a signal identification approach: a simulation study.

There is a dearth of safety data on maternal outcomes after perinatal medication exposure. Data-mining for unexpected adverse event occurrence in existing datasets is a potentially useful approach. One method, the Poisson tree-based scan statistic (TBSS), assumes that the expected outcome counts, based on incidence of outcomes in the control group, are estimated without error.

Trust but Verify: Lessons Learned for the Application of AI to Case-Based Clinical Decision-Making From Postmarketing Drug Safety Assessment at the US Food and Drug Administration.

Adverse drug reactions are a common cause of morbidity in health care. The US Food and Drug Administration (FDA) evaluates individual case safety reports of adverse events (AEs) after submission to the FDA Adverse Event Reporting System as part of its surveillance activities. Over the past decade, the FDA has explored the application of artificial intelligence (AI) to evaluate these reports to improve the efficiency and scientific rigor of the process.

Postmortem imaging reveals patterns of medial temporal lobe vulnerability to tau pathology in Alzheimer's disease.

Our current understanding of the spread and neurodegenerative effects of tau neurofibrillary tangles (NFTs) within the medial temporal lobe (MTL) during the early stages of Alzheimer's Disease (AD) is limited by the presence of confounding non-AD pathologies and the two-dimensional (2-D) nature of conventional histology studies. Here, we combine ex vivo MRI and serial histological imaging from 25 human MTL specimens to present a detailed, 3-D characterization of quantitative NFT burden measures in the space of a high-resolution, ex vivo atlas with cytoarchitecturally-defined subregion labels, that can be used to inform future in vivo neuroimaging studies. Average maps show a clear anterior to poster gradient in NFT distribution and a precise, spatial pattern with highest levels of NFTs found not just within the transentorhinal region but also the cornu ammonis (CA1) subfield.

Prolonged Diabetic Ketoacidosis Associated With Sodium-Glucose Cotransporter-2 Inhibitors: A Review of Postmarketing Cases.

Objective: To describe reported cases of prolonged or relapsed ketoacidosis (KA) in adults with type 2 diabetes receiving treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors.

Methods: We performed a search of the U.S.

Fibrosing colonopathy associated with cysteamine bitartrate delayed-release capsules in cystinosis patients.

Background: The objective of this report is to identify and characterize cases of fibrosing colonopathy, a rare and underrecognized adverse event, associated with cysteamine delayed-release (DR) in patients with nephropathic cystinosis.

Methods: We searched the U.S.

Sociodemographic Characteristics of Adverse Event Reporting in the USA: An Ecologic Study.

Introduction: The Food and Drug Administration Adverse Event Reporting System (FAERS) is a vital source of new drug safety information, but whether adverse event (AE) information collected from these systems adequately captures experiences of the overall United States (US) population is unknown.

Objective: To examine determinants of consumer AE reporting in the USA.

Methods: Five-year AE reporting rate per 100,000 residents per US county were calculated, mapped, and quartiled for AE reports received directly from consumers between 2011 and 2015.

Characterization of Pediatric Reports in the US Food and Drug Administration Adverse Event Reporting System from 2010-2020: A Cross-Sectional Study.

Introduction: The Food and Drug Administration Adverse Event Reporting System (FAERS) is a database of adverse event (AE) and medication error reports for drugs and therapeutic biologics. Examining trends of reported individual case safety reports (ICSRs) provides context for evaluating safety concerns.

Objective: Characterize pediatric FAERS ICSRs and compare trends (1) to adult reports; (2) within pediatric subgroups.

High seropositivity against NDO-LID in a group of household contacts of leprosy patients. Are we close to leprosy elimination in Colombia?

Introduction: Leprosy is a chronic infectious disease caused by two mycobacteria (Mycobacterium leprae and Mycobacterium lepromatosis). The household contacts (HHC) of leprosy index cases are at higher risk of being infected with these mycobacteria. Therefore, serological testing in HHC would be an effective strategy to eliminate leprosy in Colombia.

Assessment of the Impact of Mandated Postmarketing Pediatric-Focused Safety Reviews on Safety-Related Regulatory Actions 2013-2019.

The US Food and Drug Administration's (FDA's) routine postmarketing drug safety monitoring may lead to safety-related labeling changes for identified risks. Additionally, the Best Pharmaceuticals for Children Act (BPCA) and Pediatric Research Equity Act (PREA) require the FDA to conduct postmarket pediatric-focused safety reviews of adverse events. The purpose of these pediatric reviews is to identify risks associated with drug or biological products 18 months after the FDA approves a pediatric labeling change pursuant to studies conducted under the BPCA or PREA.

Benzonatate Exposure Trends and Adverse Events.

Background And Objectives: Adverse events (AE), including death, occur in children with benzonatate use. This study aims to understand recent trends in benzonatate exposure and clinical consequences in pediatric patients.

Methods: This retrospective analysis of data from IQVIA pharmacy drug dispensing, National Poison Data System, National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance Project, FDA Adverse Event Reporting System, and the medical literature evaluated exposure trends and medication-related AEs with benzonatate.

Monitoring Drug Safety in Pregnancy with Scan Statistics: A Comparison of Two Study Designs.

Background: Traditional surveillance of adverse infant outcomes following maternal medication exposures relies on pregnancy exposure registries, which are often underpowered. We characterize the statistical power of TreeScan, a data mining tool, to identify potential signals in the setting of perinatal medication exposures and infant outcomes.

Methods: We used empirical data to inform background incidence of major congenital malformations and other birth conditions.

Challenges and opportunities for mining adverse drug reactions: perspectives from pharma, regulatory agencies, healthcare providers and consumers.

Monitoring drug safety is a central concern throughout the drug life cycle. Information about toxicity and adverse events is generated at every stage of this life cycle, and stakeholders have a strong interest in applying text mining and artificial intelligence (AI) methods to manage the ever-increasing volume of this information. Recognizing the importance of these applications and the role of challenge evaluations to drive progress in text mining, the organizers of BioCreative VII (Critical Assessment of Information Extraction in Biology) convened a panel of experts to explore 'Challenges in Mining Drug Adverse Reactions'.

Novel methods for pregnancy drug safety surveillance in the FDA Sentinel System.

Purpose: It is a priority of the US Food and Drug Administration (FDA) to monitor the safety of medications used during pregnancy. Pregnancy exposure registries and cohort studies utilizing electronic health record data are primary sources of information but are limited by small sample sizes and limited outcome assessment. TreeScan™, a statistical data mining tool, can be applied within the FDA Sentinel System to simultaneously identify multiple potential adverse neonatal and infant outcomes after maternal medication exposure.

Postmarket Assessment for Drugs and Biologics Used in Dermatology and Cutaneous Adverse Drug Reactions.

Postmarket surveillance is critical for the identification of rare safety risks, which are unlikely to be identified during clinical trials and the drug development program. Rare adverse drug reactions with the potential for serious outcomes, including fatalities, include the severe cutaneous adverse reactions of Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. Dermatologists play an important role in the diagnosis of these serious drug reactions and contribute to drug safety by reporting cases of suspected cutaneous adverse drug reactions.

[Ovarian reserve and premature ovarian failure in girls and adolescents after hematopoietic stem cell transplantation].

Introduction: The increased survival of children and adolescents after Stem Cell Transplantation (SCT) has allowed us to gain a better understanding of the late effects that this procedure might have.

Objective: to measure ovarian function and reserve after SCT.

Patients And Method: A descriptive, observatio nal, and cross-sectional study of girls and adolescents with SCT between 1999 and 2011.

Sources of Evidence Triggering and Supporting Safety-Related Labeling Changes: A 10-Year Longitudinal Assessment of 22 New Molecular Entities Approved in 2008 by the US Food and Drug Administration.

Introduction: New safety issues concerning US FDA-approved drugs are commonly communicated through safety-related labeling changes. Therefore, to optimize and refine postmarket safety surveillance strategies, it is important to comprehensively characterize the sources of data giving rise to safety-related labeling changes.

Objectives: Our objective was to characterize the sources of data triggering and supporting the identification of new safety risks of FDA-approved drugs communicated through safety-related labeling changes.

Ex vivo MRI atlas of the human medial temporal lobe: characterizing neurodegeneration due to tau pathology.

Tau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer's disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we compared high-resolution ex vivo MRI scans of human postmortem MTL specimens with histology-based pathological assessments of the MTL. MTL specimens were obtained from twenty-nine brain donors, including patients with AD, other dementias, and individuals with no known history of neurological disease.

Leveraging Case Narratives to Enhance Patient Age Ascertainment from Adverse Event Reports.

Introduction: Missing age presents a significant challenge when evaluating individual case safety reports (ICSRs) in the FDA Adverse Event Reporting System (FAERS). When age is missing in an ICSR's structured field, it may be in the report's free-text narrative.

Objectives: This study aimed to evaluate the performance and assess the potential impact of a rule-based natural language processing (NLP) tool that utilizes a text string search to identify patients' numerical age from unstructured narratives.

Feature engineering and machine learning for causality assessment in pharmacovigilance: Lessons learned from application to the FDA Adverse Event Reporting System.

Background: Our objective was to support the automated classification of Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) reports for their usefulness in assessing the possibility of a causal relationship between a drug product and an adverse event.

Method: We used a data set of 326 redacted FAERS reports that was previously annotated using a modified version of the World Health Organization-Uppsala Monitoring Centre criteria for drug causality assessment by a group of SEs at the FDA and supported a similar study on the classification of reports using supervised machine learning and text engineering methods. We explored many potential features, including the incorporation of natural language processing on report text and information from external data sources, for supervised learning and developed models for predicting the classification status of reports.

A case series analysis of serious exacerbations of viral hepatitis and non-viral hepatic injuries in tocilizumab-treated patients.

Background And Aims: Reports of moderate to severe liver injury associated with tocilizumab, an interleukin-6 (IL-6) receptor antagonist, have been reported in the post-marketing setting. This case series aims to characterize cases of tocilizumab-associated clinically significant hepatic injury.

Methods: We analysed cases of severe acute liver injury associated with tocilizumab reported in the FDA Adverse Event Reporting System and the medical literature.

Complementary Use of U.S. FDA's Adverse Event Reporting System and Sentinel System to Characterize Direct Oral Anticoagulants-Associated Cutaneous Small Vessel Vasculitis.

Background: Cutaneous small vessel vasculitis (CSVV) has been reported after exposure to direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, apixaban, and edoxaban.

Objective: We used the U.S.

An Evaluation of Postmarketing Reports with an Outcome of Death in the US FDA Adverse Event Reporting System.

Introduction: Adverse reactions with an outcome of death are inherently important for pharmacovigilance organizations to evaluate. Prior efforts to systematically evaluate individual case safety reports (ICSRs) with an outcome of death have been limited to high-level summaries.

Objective: The aim of this study was to characterize ICSRs with an outcome of death contained in the US FDA Adverse Event Reporting System (FAERS) database.

Towards Automating Adverse Event Review: A Prediction Model for Case Report Utility.

Introduction: The rapidly expanding size of the Food and Drug Administration's (FDA) Adverse Event Reporting System database requires modernized pharmacovigilance practices. Techniques to systematically identify high utility individual case safety reports (ICSRs) will support safety signal management.

Objectives: The aim of this study was to develop and validate a model predictive of an ICSR's pharmacovigilance utility (PVU).

Drug Interaction Between Febuxostat and Thiopurine Antimetabolites: A Review of the FDA Adverse Event Reporting System and Medical Literature.

Background: There is a known drug interaction (DI) between xanthine oxidase (XO) inhibitors and the thiopurine immunosuppressants, azathioprine (AZA) and mercaptopurine (6-MP). Xanthine oxidase inhibition increases concentrations of AZA and 6-MP active metabolites, possibly resulting in myelosuppression. When allopurinol is used with AZA or 6-MP, dose reduction of AZA or 6-MP is recommended.