Consumer wearable devices are commonly used by patients and consumers for several reasons with increasing application as new technologies are developed. Use of these devices is an emerging issue in Neurology because of increased adoption and the additional data reported to providers by patients. Understanding of possible functions, limitations, and effect on patients of non-US Food and Drug Administration (FDA)-cleared wearable technology to inform neurologic care is needed. A common theme in people with neurologic conditions regarding consumer wearables and associated tracking applications is that there is significant promise in these tools, but adherence (days per use/per week), continued engagement (attrition), and unintended consequences such as heightened anxiety remain important issues. Further understanding and validation of these devices is needed within the field of Neurology before full use and confidence can be achieved. Below, we provide examples of non-FDA-cleared wearable devices used in Neurology in the areas of epilepsy, headache, cardiac monitoring, and sleep.

A core mission of the US Food and Drug Administration (FDA) is to advance public health through regulatory decision-making, demanding both scientific expertise and political judgment. Since its inception, the FDA has undergone frequent reform intended to better position the agency to fulfill its mission with attention to evidentiary standards, patient autonomy and protection, innovation and access, transparency, and independence. The FDA is situated within the executive branch, so it is reasonable for the agency's priorities and approach to change with administrations. However, the scope, number, and magnitude of changes in the second Trump administration have been extraordinary, including tremendous loss of expert staff and leadership, proposals for rushed reviews and approvals based on little evidence, “expert panels” lacking public input and conflict-of-interest vetting, and political interference in lieu of established science and procedures. Scientific rigor and public trust in the FDA's decisions are at stake. Yet this crisis may offer an opportunity to rebuild and reenvision the FDA for the future. This article proposes that developing a core set of principles and associated metrics can shape rebuilding and reform by providing a framework for guiding FDA policy choices, a shared evaluative structure for assessing agency actions, and parameters for differentiating reasonable policy changes from unreasonable ones.

Repurposing dronedarone for colorectal cancer therapeutic via suppression of the AKT/ERK signaling pathways.

PBPK Modeling Addresses Oral Absorption-Mediated Drug Interactions.

Clascoterone 1% in the Treatment of Acne: A Review of its Efficacy, Safety, and Therapeutic Positioning.

Using a reconstructed human vaginal epithelium model to assess irritation: A proof-of-concept study supporting regulatory qualification of the method for use with personal lubricants.

CAR-T/NK/M-based combination therapies in cancer: A comprehensive review.

The goal of the presented methodology was to evolve and verify a simple, environmentally friendly, white HPLC stability-indicating technology that can identify the mutagenic contaminant allyl bromide in both raw materials and parenteral rocuronium bromide medications. The mobile phase composition was ethyl alcohol and double-distilled water in a ratio of 35%:65% at a flow rate of 1.0 mL/min. The linearity range concentrations of allyl bromide were 1.25-10 μg/mL. The injectable volume was 20 μL, and the injection run time and total run time were less than 9 min. With a retention time of allyl bromide at 7.11 min, the detection wavelength was 210 nm. The method's BAGI degree was 77.5, the MoGAPI degree was 82 with seven green sections, the final AES degree was 87, the AGSA degree was 80.56, the CaFRI degree was 86, the CACI degree was 77, and the whiteness score was 97.1. The HPLC method features simple implementation, environmental sustainability, and compliance with ICH Q2(R2), ICH M7, and US FDA validation criteria. It offers advantages like shorter retention time, reduced reagent use, microscale sample preparation, and lower costs compared to complex systems like UPLC-MS.

Rapid Detection of Erythrosine (FD&C Red 3) in Candy Using a Paper-Based SERS Substrate and a Handheld Raman Spectrometer.

Contrasting sources of dietary intake of cobalt and lead in the mining region of Katanga, DR Congo: a duplicate meal study.

Appendiceal cancer (AC) is a rare malignancy that often presents at advanced stages with significant histological variability influencing clinical outcomes. Precise genomic profiling is essential for accurate diagnosis and personalized patient management. This study interrogated DNA from appendiceal tumor tissue, buffy coat cells, and the cell-free DNA component of plasma using a 523-gene panel for comprehensive genomic profiling (CGP) to identify cancer-related genetic mutations in tumor and blood, evaluate tumor mutation burden, and determine genetic markers associated with histologic grade. A total of 73 patients provided blood samples comprising cell-free DNA (cfDNA) and germline buffy coat cells (bcDNA) for analysis compared with tumor tissues available from 56 of these patients. Concordance of mutations between matched tumor tissue and plasma samples (n = 51) was assessed and tumor-specific and germline variants were classified using OncoKB™ clinical criteria to delineate oncogenic and therapeutically actionable variants [level 1 mutations with U.S. Food and Drug Administration (FDA)-approved therapy]. Additionally, cfDNA concentrations were tested for association with clinical and pathologic features and oncologic outcome including disease-specific (DSS) and progression-free (PFS) survival. Circulating tumor DNA (ctDNA) from plasma cell-free DNA demonstrated high concordance with tumor genomic profiling, reaching 98.4% concordance [median, interquartile range (IQR) 13.5, 21.5] overall and 85.7% (IQR 64.6, 100) for therapeutically actionable level 1 mutations. Prevalent appendiceal tumor-specific mutations included KRAS proto-oncogene, GTPase (KRAS) (41%), GNAS complex locus (GNAS) (30%), tumor protein p53 (TP53) (30%), and SMAD family member 4 (SMAD4) (29%). Tumor-specific TP53, SMAD4, and spectrin alpha, erythrocytic 1 (SPTA1) mutations strongly correlated with intermediate and high-grade histology, whereas GNAS mutations predominated in low-grade tumors. Germline analysis identified coding mutations shared among this patient cohort in notch receptor 4 (NOTCH4) (55%) and BRCA1 associated RING domain 1 (BARD1) (48%) genes, with zinc finger homeobox 3 (ZFHX3) (29%) and adhesion G protein-coupled receptor A2 (ADGRA2), DNA polymerase epsilon (POLE), and transcription factor 3 (TCF3) mutations (all = 23%) specifically enriched in intermediate and high-grade AC. Both histological grade and cfDNA stratified by concentration tertiles independently predicted progression-free and disease-specific survival. Plasma samples exhibited consistently lower variant allele frequencies than solid tumors, limiting sensitivity for discovery of novel mutations exclusively from plasma. This study supports integrating comprehensive ctDNA assays into standard diagnostic and treatment pathways for AC using large gene panels. TP53, SMAD4, SPTA1, and GNAS mutations serve as prospective tumor-specific molecular classifiers for histological grade, while germline variants in NOTCH4 and BARD1 may further influence disease biology, with ZFHX3, ADGRA2, POLE, and TCF3 affecting grade stratification. Overall cfDNA concentration may serve as a potential prognostic biomarker in AC.

Polyethylene glycol (PEG) hydrogel dural sealants (DuraSeal, Adherus) reinforce dural closure, but case reports describe cerebrospinal fluid (CSF) leak, infection, and swelling-related neurologic injury. We characterized post-market safety in the Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database, comparing structured problem codes with negation-aware narrative review. MAUDE reports from January 1, 2015, to June 30, 2024, mentioning either device were extracted and deduplicated by unique identifiers (MDR_REPORT_KEY, REPORT_NUMBER). Structured FDA patient and device problem codes were mapped to clinical categories (CSF leak, infection, wound dehiscence, neurologic deficit, swelling/mass effect, polymerization/application issue, adhesion, reoperation/hospitalization). Narratives underwent deterministic, negation-aware screening for the same categories, and for each device we calculated event proportions. After deduplication, 279 reports were analyzed (256 DuraSeal, 23 Adherus). Most were coded as injury or malfunction; deaths were rare. CSF leak was the most frequent signal (DuraSeal 26.2% structured vs. 27.0% narrative; Adherus 52.2% vs. 47.8%). For DuraSeal, narrative review nearly doubled infection reports (8.2% vs. 19.9%) and identified swelling/mass effect (9.4%), neurologic deficit (4.3%), and reoperation/hospitalization (7.8%) largely absent from structured codes. For Adherus, narrative review identified isolated reports of infection, swelling/mass effect, and reoperation. PEG hydrogel dural sealants show post-market safety patterns dominated by CSF leak, suspected infection, and swelling-related neurologic events. Exclusive reliance on structured MAUDE codes underestimates key complications. Integrating structured fields with negation-aware narrative review yields a more complete safety profile and supports cautious use in constrained intracranial spaces.

In 2023, Esco Bars was the second most commonly reported e-cigarette brand used among US middle and high school student e-cigarette users. These products have not been authorized for sale in the United States by the US Food and Drug Administration (FDA). On May 12, 2025, and May 25, 2023, the FDA issued an import alert and a warning letter, respectively, to the manufacturer requiring them to immediately remove these unauthorized products from the market. On June 22, 2023, and July 27, 2023, the FDA also issued warning letters to US retailers and distributors, respectively, regarding the illicit sale of these unauthorized products. This study evaluated the impact of these advisory and enforcement actions on retail sales of Esco Bars in the United States. We evaluated the impact of these 2023 FDA advisory and enforcement actions on illicit sales of unauthorized Esco Bars to better inform future regulatory decision-making. This study used a synthetic control method to evaluate the impact of 2023 FDA advisory and enforcement actions on Esco Bars sales based on weekly sales data from the NielsenIQ Retail Measurement Service between January 1, 2023, and December 30, 2023. Data came from the 48 contiguous states and were not available for internet and vape shop sales. First, we standardized the data by transforming the weekly sales into z scores. Second, we created a synthetic comparison for Esco Bars sales based on sales of other e-cigarettes for which the FDA did not take action during the analytical period. Finally, we calculated the difference in sales between Esco Bars and the comparison group before and after the FDA actions. To assess the robustness of the findings, we used other standardization methods for sensitivity analyses. By the last week of 2023, actual Esco Bars' weekly sales were 68.5% lower than the estimated sales in the comparison group (P=.02). Over the 5-month period following FDA advisory and enforcement actions, Esco Bars product sales were reduced by approximately 1.7 million equivalized units (P=.06). These findings were robust across sensitivity analyses. The FDA's advisory and enforcement actions substantially reduced sales of Esco Bars products in the United States, with a sustained impact noted over a 5-month period. These findings underscore the importance and impact of FDA actions against unauthorized tobacco products as part of a comprehensive regulatory approach.

Histotripsy represents a paradigm shift in interventional oncology (IO) as the first non-invasive, non-ionising and non-thermal ultrasound-based ablation technology available for cancer therapy. Compared with thermal ablation techniques, advantages of histotripsy include tissue-selective ablation near critical structures, reduced collateral injury risk, and treatment which is unaffected by the heat sink phenomenon, ensuring predictable treatment margins. Ultrasound technology can be constrained by tissue attenuation depending on the depth of the target; however, the early phase feasibility and pivotal trial results have been promising for its application in liver cancers, with emerging translational trials in renal and pancreatic cancer. In the UK, two well-established IO sites have participated in the pivotal #HOPE4LIVER Trial that led to approval by the U.S. Food and Drug Administration (FDA) in liver tumours therapy in 2023 and obtained Medicines and Healthcare products Regulatory Agency (MHRA) Unmet Clinical Need Authorisation (UCNA) for treatment of liver tumours in UK (April, 2025) via the Innovative Devises Access Pathway (IDAP). The global-first feasibility in renal cancer (CAIN trial) was also led by the UK and completed in April 2024. This review provides an overview of histotripsy and highlights the clinical challenges in early NHS adoption such as the learning curve for operators and teams, regulatory processes, and synthesis of health economic evidence required for wider NHS commissioning. The review will also discuss the future directions of histotripsy, including combination immunomodulatory therapies, highlighting the need for continual national collaboration for successful integration in the NHS. Successfully integrating this technology into the NHS hinges on a unified national effort to navigate the clinical, regulatory and economic hurdles, ensuring its benefits reach patients nationwide.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of pancreatic β-cells and the subsequent loss of insulin production. The regeneration of pancreatic β-cells from induced pluripotent stem cells (iPSCs) represents a promising therapeutic approach for restoring β-cell function in T1DM patients. However, ensuring the safety, functionality, and genetic stability of iPSC-derived β-cells is crucial for their clinical application. To address this challenge, a comprehensive literature review was conducted using PubMed/MEDLINE, Web of Science, and Scopus databases to identify relevant studies published up to October 2025. It included an analysis of key regulatory documents from the U.S. Food and Drug Administration (FDA), the European Medicines Agency on Advanced Therapy Medicinal Products (EMA ATMP), and the International Organization for Standardization (ISO). This article proposes a comprehensive quality control (QC) strategy for differentiating iPSCs into pancreatic β-cells, emphasizing a tiered approach with multiple checkpoints throughout the process. The strategy integrates advanced molecular and functional assays to evaluate cell identity, viability, stability, and microbiological safety. The proposed QC framework allows for continuous monitoring, early detection of potential issues, and real-time adjustments to optimize the differentiation process. The flexibility of this approach ensures its adaptation to emerging scientific advancements and regulatory requirements. This integrated and adaptable QC strategy enhances the likelihood of success in generating functional β-cells, laying a solid foundation for the clinical application of iPSC-derived β-cell therapies and offering hope for effective, long-term treatments for T1DM.

Background: Local delivery after resection of high-grade glioma, particularly glioblastoma (GBM), aims to increase intratumoral drug exposure while limiting systemic toxicity. The only U.S. Food and Drug Administration (FDA)-approved implantable intracranial chemotherapy is the carmustine (1,3-bis[2-chloroethyl]-1-nitrosourea; BCNU)-impregnated polyanhydride wafer (Gliadel wafer), indicated for newly diagnosed high-grade glioma and recurrent GBM. More than two decades of clinical use and randomized data show that intracavitary chemotherapy is feasible and confers a modest survival benefit in carefully selected patients. Nevertheless, Gliadel wafer has not altered the overall poor prognosis of GBM because of biological resistance to nitrosoureas, constrained brain-parenchymal pharmacokinetics, and device-related adverse effects. Objective: The aim is to synthesize clinical and preclinical evidence defining the current limitations of Gliadel wafer and to outline strategies for next-generation local delivery systems, with emphasis on GBM within the broader high-grade glioma setting. Methods: A narrative review of randomized and observational clinical studies, pharmacokinetic studies, and preclinical investigations evaluating Gliadel wafer and potential next-generation local delivery systems in GBM and other high-grade gliomas was performed. Results: The literature delineates key limitations of Gliadel wafer: short diffusion distances and burst-weighted carmustine release, high tumor cell resistance to carmustine due to heterogeneity, and device-related side effects. Emerging approaches to address these limitations include (i) multidrug systems with synergistic effects against GBM cells; (ii) advanced biomaterials that enable controlled and sustained release; and (iii) targeted agents with minimal off-target effects. Testing newer generations of local drug-delivery systems in more predictive translational models, such as patient-derived organoids and spontaneous large-animal glioma models, is essential to maximize the translatability of preclinical studies to human studies. However, broader adoption of spontaneous large-animal glioma models is constrained by ethical oversight, animal-welfare considerations, cost, and limited availability compared with rodent platforms. Conclusions: Next-generation local drug-delivery systems should include multiple synergistic tumor-selective drugs that can be released in a controlled, sustained manner deep into the residual tumor. Preclinical testing of these systems should be conducted in clinically relevant animal models that are more translatable than those used in early Gliadel wafer studies.

Model-informed drug development (MIDD) is a regulatory-endorsed approach that streamlines drug discovery, development, and approval. Actively promoted by the U.S. Food and Drug Administration (FDA), it integrates quantitative modelling to support decision-making across drugs, generics, and biologics. This study aims to highlight the applications, benefits, and future perspectives of MIDD in optimizing clinical trial design, supporting regulatory review, advancing biopharmaceutics, and enabling innovation in emerging therapeutic areas. Current applications of MIDD were evaluated, focusing on its role in new drug development, generic drug approval, biopharmaceutics, and early exploration in cell and gene therapy. The study emphasizes computational modelling, dose optimization, clinical trial refinement, and postapproval lifecycle management strategies. MIDD has demonstrated considerable impact in optimizing dose selection, refining trial design, and addressing regulatory concerns regarding efficacy and safety. In the field of biopharmaceutics, computational modelling has guided formulation development and facilitated subsequent in vivo studies. In genetics, mathematical modelling has enabled efficient development and approval of complex formulations, reducing both time and cost. MIDD shows strong potential for quantitatively analysing biological activity, pharmacodynamics, transgene expression, immune responses, safety, and therapeutic effectiveness. MIDD is a transformative approach in drug development, offering robust tools for decision- making and regulatory assessment. Its broader implications across therapeutic domains are expected to enhance innovation, improve patient outcomes, and reduce development costs. Future advancements, particularly in cell and gene therapy, will further expand its role as a cornerstone of drug development.

Global regulation of artificial intelligence (AI) in healthcare remains highly fragmented. Over 1,000 national AI-related regulations and policy frameworks have been introduced across more than 70 countries, most originating from high-income nations. While major drug regulatory authorities, including those in the United States and European Union, and others like WHO, have issued guidance on AI-enabled systems, platforms, and products, no unified source exists that compiles or compares how these bodies govern the broader AI-enabled therapeutic ecosystem. This lack of alignment contributes to disparities in interpretation and implementation, potentially delaying global access to novel AI-based therapies. To address this gap, we developed AI-enabled, continuously updated regulatory intelligence system (AICURIS), a comprehensive AI-enabled regulatory intelligence system trained initially on AI-related regulations from sentinel regulatory authorities (e.g., FDA, EMA, WHO), designed to continuously monitor and classify AI-relevant regulatory content and to enable structured comparison, identification of alignment and divergence, and evidence-informed discussion on regulatory convergence as its coverage expands across jurisdictions. Using over 400,000 regulatory documents published since 2019, an AI-enabled hybrid semantic similarity and keyword scoring model achieved 95% recall for high-confidence AI-related content. The following results summarize the key findings from the analysis of AI-related regulatory documents across three major agencies (United States Food and Drug Administration (FDA), European Medicines Agency (EMA), and the World Health Organization (WHO)). The findings are presented in six parts: (1) document corpus composition and filtering outcomes, (2) model optimization, (3) classification model performance, (4) classification ensemble model validation, (5) cross-agency bias mitigation, and (6) real-time monitoring capabilities. This study demonstrates that AI-powered, data-driven approaches can effectively federate AI-related drug regulations across jurisdictions, reducing global disparities, and enabling more equitable, collaborative, and efficient human therapeutics innovation.

Veterinary graduates must be prepared to educate clients about medications and supplements. We surveyed 1955 Dog Aging Project newsletter recipients and 40 final-year veterinary students at Texas A&M College of Veterinary Medicine and Biomedical Sciences on their perceptions about medications and supplements. Respondents indicated whether each of 13 attributes applied to medications, supplements, neither, both, or "I'm not sure." Frequency of responses by newsletter recipient respondents versus student respondents, respectively, were evaluated. We observed differences in the majority response for: (1) target a specific ailment (51% for newsletter recipients versus 62% for students, respectively); (2) target a specific condition (54% vs. 40%); (3) promote health and wellness (51% vs. 38%); (4) prevent worsening of a condition (60% vs. 72%); (5) are added to food (58% vs. 80%); (6) are recommended by a veterinarian (58% vs. 82%); (7) are covered by pet insurance (57% vs. 80%); and (8) are given to the animal long term or lifelong (55% vs. 72%). The overall distribution of responses was statistically significantly different between groups for three attributes: added to food (p < 0.001); recommended by a veterinarian (p = 0.005); and covered by pet insurance (p < 0.001). While a majority of both groups recognized that only medications are tested and approved by the Food and Drug Administration (FDA), 15% of final-year veterinary students indicated that they thought both supplements and medications are FDA regulated, which suggests an important educational gap.

This study aimed to assess the spectrum and frequency of adverse events (AEs) linked to glucagon-like peptide-1 receptor agonists (GLP-1RAs) using the US FDA Adverse Event Reporting System (FAERS). Emphasis was placed on emerging safety concerns in context-specific use. A retrospective analysis of FAERS reports between 2012 and 2025 was conducted. Five commonly prescribed FDA-approved GLP-1RAs were included. Disproportionality analyses were applied to detect AE signals. Subgroup analyses evaluated associations by indication, GLP-1RAs compared to other drugs, and AEs specific to individual GLP-1RAs. From over 18 million FAERS reports, 137,451 involved GLP-1RAs. The most frequent AEs were gastrointestinal, nutritional and metabolic, and psychiatric disorders, occurring at higher rates compared to other drugs. In diabetes use, GLP-1RAs were associated with retinopathy, hearing loss, and cataracts. In contrast, when prescribed for weight management/obesity, nutritional, metabolic, and psychiatric AEs predominated. We also developed an open-access portal for AE exploration, available at http://glp1.tanlab.org. GLP-1RAs are linked to a broad range of AEs across indications. These findings stress the need for careful clinical monitoring and long-term safety evaluation. This study also illustrates how real-world evidence can inform safety communications, as well as hypothesis generation for research on next-generation GLP-1RAs.