Claims-based analyses can suffer from residual and unmeasured confounding due to factors that are poorly captured in claims. Some of these factors may be measured in other data sources, such as in structured fields of electronic health records (EHR), for example, laboratory test results, or in free-text physician notes. We conducted a proof-of-principle study to demonstrate a process for evaluating the potential risk of confounding-factors poorly captured in claims data but measurable in the EHR as part of drug safety surveillance activities. In future practical applications, this approach could be used along with other sensitivity analyses to evaluate potential residual confounding (e.g., E-values, negative controls). We used claims-EHR linked data from the Mass General Brigham site of the US Food and Drug Administration's (FDA) Sentinel Real World Evidence Data Enterprise. We extracted a cohort that was previously used in a prototypical Sentinel claims-based query that compared initiators of sacubitril-valsartan vs. angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on the risk of angioedema. In this cohort, we used EHR data to characterize angioedema risk factors poorly captured in claims and observed that claims-based proxies balanced most risk factors that were measurable only in EHR data. While quantitative bias analysis methods can be used to adjust for residual confounding using external information on magnitude and direction of bias, this was deemed unnecessary for this example due to the observed balance achieved on risk factors for angioedema measured in the EHR. A robust linked EHR-claims data infrastructure is crucial for routine application of these methods to evaluate and mitigate residual confounding in drug safety surveillance studies.

Effects of nonpharmacological manipulations and repeated xanomeline treatment on methamphetamine-vs-food choice in Sprague Dawley and Long Evans rats.

The increasing popularity of chicken-based street food among low-to-middle-income consumers in the City of Mati, Davao Oriental, Philippines, raises serious health concerns due to the potential risk of foodborne illnesses. Despite rising poultry consumption, microbial assessment of street-vended chicken products is not routinely conducted, creating a significant knowledge gap in local food safety monitoring. This study aimed to determine the presence of Salmonella spp. in fresh chicken meat and isaw and Escherichia coli (Migula, 1895) in fried chicken, “isaw,” and “kwek-kwek” sold by randomly selected street vendors. Samples were collected using standard aseptic techniques. Salmonella Shigella agar and Eosin methylene blue (EMB) agar were used to identify the target bacteria. The most probable number (MPN) method, based on Department of Agriculture-National Meat Inspection Service (DA-NMIS) Circular No. 9-2008-5, was used to detect the presence of E. coli in fresh chicken meat. Total plate count (TPC) was used to detect the presence of Salmonella spp. in fresh chicken meat and isaw and to detect E. coli in fried chicken, “isaw,” and “kwek-kwek,” following standards set by DA-NMIS and the Department of Health-Food and Drugs Administration (DOH-FDA) Circular No. 2022-12-2. The results showed Salmonella spp. in all fresh chicken and “isaw” samples, exceeding the DA-NMIS absence requirement in 25 g. Escherichia coli in fresh chicken meat was within the 500 MPN g-1 limit. However, TPC values in fried chicken, “isaw,” and “kwek-kwek” exceeded the 100 CFU g-1 DOH-FDA limit. These findings revealed significant bacterial contamination in fresh chicken meat and popular chicken-based street foods, underscoring the urgent need for stronger implementation of regulation, regular microbial monitoring, and food safety education to support local public health efforts and guide future policy enhancement.

Approximately 1-2% of patients undergoing hip or knee arthroplasty encounter a periprosthetic joint infection (PJI). Currently, the treatment involves revision surgeries and long-term antibiotic therapy. However, too low antibiotic concentrations can lead to treatment failure, whereas excessively high concentrations can lead to adverse events. Although optimal dosing is very important, there remains an insufficient understanding of the relationship between the concentrations of the plasma and antibiotics at the target site. This study aimed to develop and validate a novel ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique for quantifying two frequently prescribed antibiotics, vancomycin and clindamycin, in synovial tissue and bone samples. Method validation was performed based on the guidelines of the European Medicines Agency (EMA) and US Food and Drug Administration (FDA). The method was found linear for vancomycin from 0.8 to 25 μg/g and for clindamycin from 0.5 to 25 μg/g in the bone and from 1 to 25 μg/g for both compounds in synovial tissue ( r2 > 0.990). The results of the validation of precision, accuracy, and carry-over were all within the acceptable ranges. All clindamycin extracts were stable in the autosampler for the bone and synovial tissue samples for up to 24 hours. Vancomycin extracts were stable in synovial tissue for up to 24 hours but not in bone sample extracts. A method for quantifying vancomycin and clindamycin in synovial tissue and bone using UHPLC-MS/MS was developed and validated.

Spatiotemporal liposome-zwitterionic nano-hydrogel orchestrates immunomodulation and neurogenesis in spinal cord injury repair.

New developments and future directions in the management of systemic lupus erythematosus.

Major advances have broadened the therapeutic landscape of inflammatory skin diseases. In psoriasis, alongside the tyrosine kinase 2 (TYK2) inhibitor deucravacitinib, the United States Food and Drug Administration (FDA) has approved the first oral interleukin-23 (IL-23) receptor antagonist peptide, icotrokinra. In atopic dermatitis, new data have emerged on stapokibart, an interleukin-4 receptor alpha subunit (IL-4Rα) inhibitor introduced in China. In hidradenitis suppurativa, glucagon-like peptide-1 receptor agonists (GLP-1 RA) are also gaining increasing attention as adjunctive therapy.

Occupational injuries are prevalent within the veterinary sector, though their true extent is unknown as evidence indicates widespread under-reporting of injuries. This study aimed to: assess injury under-reporting across roles in a group of UK veterinary practices; and audit the type, frequency, and outcomes of workplace injuries within a large veterinary organisation. A retrospective audit was conducted on a large veterinary organisation's accident reporting system in 2022. Under-reporting was estimated using a modified capture-recapture method, comparing audit records with self-reported injury data from a cross-sectional staff survey stratified by role and employment figures. Audit data were descriptively analysed and compared with survey data. The overall injury under-reporting rate was 68.9%; for every 100 workplaces injuries, 69 went un-reported. Levels of under-reporting were higher in companion animal practices (70.0%) than large animal practices (56.4%). Common causes of injury of companion animal staff included; clinical examination (28.2%); falls, slips and trips (11.2%); drug administration (10.4%), and needlesticks and surgical sharps injuries (6.1%). Survey responses could not be directly linked to audit records due to anonymity, and survey-based prevalence estimates assumed only one injury per person per year, likely underestimating true injury rates. Occupational injury under-reporting is likely widespread in UK veterinary practices, particularly companion animal practices. Without improving reporting, it will be challenging to establish the true incidence and context of occupational injuries in the veterinary workforce. Strengthening reporting, training, leadership engagement, and visible responses to incidents are key to strengthening safety culture and injury reporting.

Standardization of clinical trials subject ID schematics: A portfolio-wide model to enhance data integrity and regulatory compliance.

The U.S. Food and Drug Administration (FDA) used an Active Postmarket Risk Identification and Analysis (ARIA) system to address a safety issue (serious infection) identified during clinical review of an application to market ustekinumab as a treatment for Crohn's disease (CD). FDA used an active-comparator new-user cohort design, data from six Sentinel Data Partners, a method developed in Sentinel for identifying serious infection, and ARIA analytic tools to estimate serious infection incidence in adult CD patients during treatment with ustekinumab or an active comparator (infliximab, adalimumab, or vedolizumab). Inverse probability of treatment weighting (IPTW) was used to control for baseline differences between treatment groups. Analyses compared ustekinumab and comparator cohorts with 15,490 and 51,503 patients, respectively. The primary composite outcome of serious infection or COVID-19 occurred in 747 ustekinumab patients (4.82 %; 44.1 per 1000 patient-years) during mean 400-day follow-up. IPTW proportional hazard (Cox) regression estimated risk in the ustekinumab cohort vs. active comparator with hazard ratio 0.88 (95% confidence interval 0.80-0.96). Findings were similar (a) according to line of therapy (use or non-use of an advanced inflammatory bowel disease therapy during a 183-day baseline period) and (b) before and after the start of the COVID-19 pandemic. Additional analyses excluded large magnitude risks from ustekinumab for major types of serious infection. In conclusion, IPTW analyses excluded large magnitude risks from ustekinumab for serious infection. This report describes the first ARIA study to use complex confounding adjustment to help resolve a safety issue identified during FDA review of a marketing application.

The expanded decision tree: Predicting chronic toxic potential and safe intake levels.

Stroke can be categorized as ischemic and hemorrhagic on the basis of its origin. The pathophysiology following a stroke is complex, and is characterized by ongoing inflammation, neuronal injury, and the accumulation of reactive oxygen species in the brain, all of which reflect a dynamic process of change. This complexity hinders achievement of significant therapeutic outcomes with standard stroke treatment procedures, limiting post-stroke recovery. This review presents an innovative post-stroke therapeutic approach that utilizes nanomedicines to modify the cerebral microenvironment. It highlights the primary roles of chronic inflammation and nerve repair issues in causing prolonged impairment in stroke patients. Traditional therapies show limited effectiveness in achieving neuroprotection, immunoregulation, and neural regeneration during the subacute and chronic phases of stroke. Therefore, effective stroke management requires the use of specific therapeutic strategies tailored to the pathological characteristics of each phase. Various types of nanomedicines possess distinct physicochemical properties and can be selected on the basis of the specific therapeutic needs. Surface-modification technologies have significantly enhanced the ability of nanomedicines to penetrate the blood-brain barrier and improve their targeting capabilities in drug administration. However, the stability, biocompatibility, and long-term safety of nanomedicines require further optimization for clinical application. Nanomedicines represent a novel approach to stroke treatment through targeted delivery and multifaceted regulatory mechanisms. These medicines provide distinct advantages, particularly in addressing chronic inflammation and promoting nerve regeneration. As a result, nanomedicines are expected to significantly improve rehabilitation outcomes and quality of life for stroke patients in the future, emerging as a crucial modality for stroke treatment.

The function and mechanism of LINC01583 on Osimertinib resistance in non-small cell lung cancer.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with few effective treatments and high clinical trial failure rates. Since 1995, only 3 drugs riluzole, edaravone, and tofersen have gained approval from the Food and Drug Administration, all offering modest benefits. Challenges in ALS drug development include poor translational preclinical models, underpowered early-phase trials, and the high cost of late-stage development. Despite federal initiatives such as the Accelerating Access to Critical Therapies for ALS Act and the ALL ALS Consortium, critical gaps remain in funding large multisite trials and sustaining research networks. Accelerating progress requires strengthening national registries, expanding adaptive trial platforms, integrating existing networks, and adopting innovative funding models such as milestone-based public-private partnerships and reinvestment of licensing revenues. A coordinated, sustainable research and funding ecosystem could transform ALS therapy development and serve as a model for advancing treatments for other rare neurodegenerative and neurogenetic disorders.

Although immune checkpoint inhibitors (ICIs) and targeted therapies (TTs) have transformed the treatment of non-small cell lung cancer (NSCLC) across disease stages, real-world access remains highly unequal worldwide. Persistent cost barriers, fragmented reimbursement frameworks, and heterogeneous regulatory pathways limit equitable availability. The rapid proliferation of me-too agents has been proposed to counter monopolies; yet, this expansion has not consistently improved affordability. Heterogeneous evidentiary requirements-along with differences in clinical end points, comparator selection, crossover policies, and treatment duration-fragment therapeutic markets and complicate assessment of incremental clinical benefit. Divergent regulatory decisions, particularly between the US Food and Drug Administration and European Medicines Agency, underscore how trial design and geographic representation influence drug availability, especially when approvals rely on single-country data sets. These challenges are amplified in perioperative treatment strategies and rare oncogene-defined subgroups, where feasibility constraints and limited clinical equipoise hinder large randomized trials. As a result, an increasingly crowded therapeutic landscape makes cross-trial comparisons difficult and allows disparities in patient access to persist despite multiple approved therapies. Dose selection has historically followed maximum tolerated dose principles, even when preclinical and pharmacologic data suggest activity plateaus at lower exposure of ICI and TT. Dose and schedule optimization-through reduced dosing, extended intervals, or other deintensified strategies-therefore represents a rational and ethically grounded approach with a meaningful clinical impact. Such strategies may preserve efficacy while improving tolerability, reducing treatment burden, and mitigating financial toxicity, particularly in resource-limited settings. Aligning regulatory frameworks with dose optimization could promote more scalable, equitable, and sustainable NSCLC innovation.

Covalent lysine targeting is coming of age.

The 2025 recommendations from the International Liaison Committee on Resuscitation are updated from the 2020 version. The algorithm is unchanged from 2015. Ten topics are addressed in the 2025 recommendations: Anticipation and preparation, Umbilical cord management, Initial steps, Assessment of heart rate at birth, Ventilation and oxygenation, Circulatory support, Drug and fluid administration, Post-resuscitation care, Prognostication during cardio-pulmonary resuscitation and Family presence. Among changes since 2020 are an update of umbilical cord handling. Assessment of heart rate is now including auscultation as well as pulse-oximetry. We identified 51 recommendations given for topics published between the 2020 and the 2025 versions. Of these, 19 were weak and only three were strong recommendations, 6 were conditional and 15 recommendations are classified as good practice. Seven had insufficient evidence to draw any conclusion, and one was not graded. The certainty of evidence was low or very low for 25 recommendations and moderate for four only. Conclusion: The present recommendations for newborn resuscitation are improved; however, they are still based on weak evidence with mostly low or very-low certainty. This indicates extensive research to establish truly evidence-based recommendations for newborn resuscitation is still needed.

Molecular Modeling and machine learning for predicting high-concentration antibody viscosity.

A Real-World Pharmacovigilance Study of Cilostazol Based on the Food and Drug Administration Adverse Event Reporting System: A Cross-Sectional Disproportionality Analysis.

Hematologic malignancies remain a significant public health concern in the United States, affecting over 1.5 million individuals. Although chemotherapy remains a foundational component of treatment, the emergence of novel therapeutic strategies has transformed the treatment landscape. This review examines the development, mechanism of action, expanding clinical applications, and barriers to care associated with chimeric antigen receptor T-cell (CAR T-cell) therapy. Relevant data was found via a literature search across major biomedical databases focusing on current clinical implementation of CAR T-cell therapies. To date, seven CAR T-cell therapies have received U.S. Food and Drug Administration approval, demonstrating robust response rates and effective clearance of malignant cells in hematologic malignancies, including B-cell lymphoma, multiple myeloma, and acute lymphoblastic leukemia. Despite these promising outcomes, CAR T-cell therapy faces significant challenges, including manufacturing timelines, geographic access limitations, and substantial financial burden. As the field continues to evolve, this review aims to provide clinicians with an updated synthesis of clinical outcomes, treatment-related toxicities, and persistent barriers to equitable access.