Search Results (535)

Randomized controlled trials (RCTs) have been regarded as the gold standard for evaluating the efficacy of treatments for chronic pain and are the foundation for regulatory approval and guideline development. However, their restrictive design and dependence on idealized populations can limit their applicability to the diverse patients seen in routine chronic pain management. Real-world data (RWD), collected from electronic medical records, registries, claims databases, and digital health platforms, can offer a more comprehensive view of treatment adherence and safety that RCTs often overlook. A key issue in pain medicine is the efficacy–effectiveness gap, where discrepancies exist between the outcomes of therapies and interventions in RCTs versus in real-world practice due to variations in patient populations and adherence. Bridging this gap ensures that observed improvements align with patients’ preferred outcomes and functional goals. Integrating the strengths of RCTs and RWD provides a more comprehensive evidence base to guide clinical decision-making, influence reimbursement policies, and develop equitable guidelines. The primary aim of this paper is to identify factors used in FDA-regulated RCTs and RWD that could be implemented or enhanced in everyday practice to deliver more holistic and patient-centered care in the management of chronic pain. Full article

Background/Objectives: Next-generation sequencing (NGS)-based molecular profiling has revolutionized personalized medicine and unlocked new treatment options for cancer patients. Clinical guideline bodies agree that patients diagnosed with HR+/HER2− metastatic breast cancer (mBC) may benefit from comprehensive somatic genomic profiling to identify candidates for established targeted therapies and clinical trials, yet many patients are not receiving it due to a lack of widespread access to NGS. Methods: To better understand the perceived barriers (if any) to NGS tests in mBC, a study was conducted across multiple stakeholders including medical oncologists, nurses, physician assistants, lab directors, pathologists, payers, and patients. Results: This study revealed that despite the awareness and recognition of the value proposition of NGS-based molecular profiling in mBC, inconsistent payer coverage, high out of pocket costs for patients, and challenges in managing reimbursement and prior authorization processes can lead to suboptimal utilization of NGS, which can subsequently lead to suboptimal treatment decisions where approved therapies exist. Interestingly, many payers (33%) were not aware of the current somatic biomarker testing recommendations from NCCN guidelines. As a result, payers identified the lack of clear clinical guidelines (74% ranked as top 3), the lack of internal consensus on which NGS tests to cover (45%), and the absence of internal expertise on NGS (39%) as the primary hurdles for broader NGS access. Conclusions: The results suggest that widespread HCP and payer education on clinical guidelines (e.g., NCCN) and utility for targeted therapy selection is crucial for enhanced adoption of NGS-based molecular profiling in mBC. Full article

A reassessment of the risk-benefit balance of the two lipid nanoparticle (LNP)-based vaccines, Pfizer’s Comirnaty and Moderna’s Spikevax, is currently underway. While the FDA has approved updated products, their administration is recommended only for individuals aged 65 years or older and for those aged 6 months or older who have at least one underlying medical condition associated with an increased risk of severe COVID-19. Among other factors, this change in guidelines reflect an expanded spectrum and increased incidence of adverse events (AEs) and complications relative to other vaccines. Although severe AEs are relatively rare (occurring in <0.5%) in vaccinated individuals, the sheer scale of global vaccination has resulted in millions of vaccine injuries, rendering post-vaccination syndrome (PVS) both clinically significant and scientifically intriguing. Nevertheless, the cellular and molecular mechanisms of these AEs are poorly understood. To better understand the phenomenon and to identify research needs, this review aims to highlight some theoretically plausible connections between the manifestations of PVS and some unique structural properties of mRNA-LNPs. The latter include (i) ribosomal synthesis of the antigenic spike protein (SP) without natural control over mRNA translation, diversifying antigen processing and presentation; (ii) stabilization of the mRNA by multiple chemical modification, abnormally increasing translation efficiency and frameshift mutation risk; (iii) encoding for SP, a protein with multiple toxic effects; (iv) promotion of innate immune activation and mRNA transfection in off-target tissues by the LNP, leading to systemic inflammation with autoimmune phenomena; (v) short post-reconstitution stability of vaccine nanoparticles contributing to whole-body distribution and mRNA transfection; (vi) immune reactivity and immunogenicity of PEG on the LNP surface increasing the risk of complement activation with LNP disintegration and anaphylaxis; (vii) GC enrichment and double proline modifications stabilize SP mRNA and prefusion SP, respectively; and (viii) contaminations with plasmid DNA and other organic and inorganic elements entailing toxicity with cancer risk. The collateral immune anomalies considered are innate immune activation, T-cell- and antibody-mediated cytotoxicities, dissemination of pseudo virus-like hybrid exosomes, somatic hypermutation, insertion mutagenesis, frameshift mutation, and reverse transcription. Lessons from mRNA-LNP vaccine-associated AEs may guide strategies for the prediction, prevention, and treatment of AEs, while informing the design of safer next-generation mRNA vaccines and therapeutics. Full article

Background: A novel triple therapy regimen for Helicobacter pylori eradication, recently approved by the U.S. FDA, comprises vonoprazan (VPN), a potassium-competitive acid blocker, in combination with amoxicillin (AMX) and clarithromycin (CMN). This study presents the development and full validation of a rapid, selective, and sensitive LC-MS/MS method for the simultaneous quantification of these three drugs in spiked human plasma. Methods: Sample preparation was performed using a simple and efficient liquid–liquid extraction (LLE) technique. Chromatographic separation was achieved within 5 min using a Phenomenex Kinetex C18 column (100 × 4.6 mm, 2.6 µm) and a gradient elution system consisting of 0.1% formic acid in water and acetonitrile. Moreover, diazepam was used as an internal standard. The mass spectrometric detection was conducted in multiple reaction monitoring (MRM) mode using positive electrospray ionization. Results: The method exhibited excellent linearity over the investigated concentration ranges (2, 5, 10, 20, 50, and 100 ng/mL for amoxicillin and clarithromycin and 5, 10, 20, 30, 50, and 100 ng/mL for vonoprazan). Intra- and inter-day precision and accuracy values met FDA bioanalytical method validation guidelines, with relative standard deviations and relative errors below 15%. Mean absolute recoveries were above 93% for all analytes. Conclusions: The developed method was fully validated, rapid, selective, and sensitive LC-MS/MS and was assessed using the AGREE tool as a greenness assessment approach, confirming its environmental friendliness and alignment with green analytical chemistry principles. Full article

Aims: This study aimed to determine the prevalence of nurses in a Latin American leadership school who meet advanced nurse standards. Design: A descriptive cross-sectional study was conducted. Methods: Data were collected between January and November 2024 from a total of 92 participants from the Latin American Leadership School of FUDEN-FEPPEN (Foundation for the Development of Nursing—Pan American Federation of Professional Nurses). The response rate was 13%. The Spanish version of the APRD (advance practice role delineation) was validated in Spanish. The study was approved by the Social Ethics Committee of UCLM (Universidad Castilla-La Mancha). Inference analysis was performed to examine factors associated with advanced practice domains. Results: A total of 92 nurses participated in the study. Among the participants, 35.86% (33 nurses) met the requirements for advanced practice nurses and the minimum training required by the International Council of Nurses. Nurses in both primary care and specialized care perform more advanced practice activities in direct care; however, nurses practicing teaching and research perform more advanced practice activities in the indirect practice domains (training, research and teaching). Conclusions: The percentage of nurses participating in the Latin American leadership school who met the standards was determined, with the most frequent domains those related to direct care, such as expert care planning, integrated care, and inter-professional collaboration. Implications for the profession and patient care: To our knowledge, this is the first study that describes the profile of advanced practice nurses in the Latin American context. This study shows that advanced practice activities exist and are practiced, but there is no clear delimitation or regulation of these activities. Reporting method: The study was conducted following the STROBE guidelines. Public contribution: This study did not include patient or public involvement in its design, conduct, or reporting. Full article

This study reviews the scientific use of chest-strap wearables, analyzing their advantages and limitations, following PRISMA guidelines. Eligible studies assessed chest-strap devices in adults and reported physiological outcomes such as heart rate, heart rate variability, R–R intervals, or electrocardiographic waveform morphology. Studies involving implanted devices, wrist-worn wearables, or lacking validation against reference standards were excluded. Searches were conducted in PubMed, Scopus, Web of Science, and ScienceDirect for studies published in the last 10 years. The quality of the studies was assessed using the Mixed Methods Appraisal Tool, and results were synthesized narratively. Thirty-two studies were included. The most frequently evaluated devices were the Polar H10 and Zephyr BioHarness 3.0, which showed strong correlations with electrocardiography at rest and during light-to-moderate activity. Reported limitations included motion artefacts, poor strap placement, sweating, and degradation of the skin–electrode interface. None of the devices had CE or FDA approval for clinical use, and most studies were conducted in controlled settings, limiting generalizability. Ergonomic concerns such as discomfort during prolonged wear and restricted mobility were also noted. Overall, chest-strap sensors showed good validity and were widely used in validation studies. However, technical refinements and large-scale field trials are needed for broader clinical and occupational application. This review is registered in PROSPERO and is part of the SIREN project. Full article

Supply chain financing offers advantages over traditional channels such as bank loans and equity financing, including greater flexibility, lower transaction costs, and simplified approval procedures. However, when a firm’s sustainability faces uncertainty, access to supply chain financing may become constrained by multiple factors, including the risk tolerance of supply chain partners, market transparency, and corporate reputation. ESG, representing Environmental, Social, and Governance standards, is a critical framework for assessing corporate sustainability performance. Given that divergent ESG evaluations reflect disparate market assessments of a firm’s sustainable development capabilities, such divergence may affect supply chain financing by altering stakeholder trust dynamics. This research examines A-share listed firms in China (2016–2022) and reveals that divergence in ESG evaluations significantly inhibits firms’ access to supply chain financing. Mechanism validation suggests that divergent ESG evaluations amplify informational opacity, operational risks, and negative reputation, thereby influencing supply chain partners’ risk perceptions and trust levels. Heterogeneity analysis shows that corporate governance quality, regional trust levels, and ESG awareness modulate the negative impact of divergent ESG evaluations on supply chain financing. The asymmetric effects of divergent ESG evaluations on supply chain financing are further confirmed, with distinct manifestations between upstream suppliers and downstream customers. By bridging gaps in existing research on divergent ESG evaluations and supply chain finance, this work offers regulatory guidelines, operational recommendations for firms, and investment decision frameworks. Full article

Introduction: Lumbar radiculopathies involving the entrapment of nerve roots in the lumbar spine are common neuropathic conditions. These conditions affect 40% to 70% of individuals in their lifetime and lead to significant medical costs. Objective: This study aims to identify clinical, psychological, and biomarker-based prognostic factors that predict functional outcomes following surgery for lumbar radiculopathy. Materials and Methods: This prospective cohort study, conducted at Hospital Central de la Defensa Gómez Ulla, Madrid (Spain), adheres to the STROBE guidelines. The study includes patients aged 18–75 with lumbar radiculopathy, confirmed by clinical diagnosis, imaging, and electromyography (EMG) findings. Exclusion criteria include previous lumbar spine surgeries and systemic diseases. The primary outcome is the Oswestry Low Back Pain Disability Questionnaire. Sample size calculations, based on a conservative effect size (f² = 0.20), determined the need for 172 participants, accounting for a 15% dropout rate and 80% power. Procedure: Patients will undergo an initial assessment, including EMG tests, sociodemographic and psychological questionnaires, blood sample tests, and physical questionnaires. This process will be repeated six months post-intervention, except for the blood sample test, expectations questionnaire, and EMG, which will be performed only once. Statistical Analyses: Data will be analyzed using Python 3.12.3, employing a multivariate linear regression analysis. Assumptions of linearity, independence, homoscedasticity, normality, and no multicollinearity will be validated. Corrective measures will be applied if assumptions are violated. Ethics and Dissemination: The study follows the Declaration of Helsinki guidelines and has been approved by the Ethics Committee of Universidad Rey Juan Carlos (070220241052024). Potential risks will be minimized, and adverse events will be recorded and addressed. Findings will be published in high-impact journals and presented at conferences. Full article

Background: Selective serotonin reuptake inhibitors (SSRIs) are one of the most frequently used medication classes in psychiatry, with many approved and off-label uses. One common side effect of SSRIs is sexual dysfunction, leading to the off-label use of SSRIs to manage inappropriate sexual behaviors in psychiatric settings. However, no official guidelines exist for this off-label use of SSRIs, so a review of this use is warranted. Methods: This review was conducted using the PubMed and Google Scholar databases. Grey literature was considered for inclusion in this review, but only one report by the United Kingdom’s Care Quality Commission was included. Peer-reviewed references discussing the theoretical mechanisms of SSRI-induced sexual dysfunction, case reports/studies examining the off-label use of SSRIs, and reviews discussing relevant disorders like post-SSRI sexual dysfunction (PSSD) were included in this review. Results: The literature proposes that SSRIs act through a variety of serotonin receptors such as 5-HT_1A, 5-HT_2A, and 5-HT_2C to inhibit dopaminergic tone in the mesolimbic and spinal pathways to cause sexual dysfunction. Discussion: SSRIs are frequently considered for off-label use in managing inappropriate sexual behavior, particularly in geriatric patients with dementia, given their superior safety profile compared to antipsychotics in that population. However, the risk and treatment options for PSSD are unclear, which poses a risk for patients taking SRRIs, as it can be a severe and enduring condition. High-quality clinical trials are needed, as the majority of the literature on the topic consists of case reports or theoretical papers. Full article

Virtual reality (VR) technology has emerged as a promising alternative to conventional perimetry for assessing visual fields. However, the clinical validity of commercially available VR-based perimetry devices remains uncertain due to variability in hardware, software, and testing protocols. A systematic review was conducted following PRISMA guidelines to evaluate the validity of VR-based perimetry compared to the Humphrey Field Analyzer (HFA). Literature searches were performed across MEDLINE, Embase, Scopus, and Web of Science. Studies were included if they assessed commercially available VR-based visual field devices in comparison to HFA and reported visual field outcomes. Devices were categorized by regulatory status (FDA, CE, or uncertified), and results were synthesized narratively. Nineteen studies were included. Devices such as Heru, Olleyes VisuALL, and the Advanced Vision Analyzer showed promising agreement with HFA metrics, especially in moderate to advanced glaucoma. However, variability in performance was observed depending on disease severity, population type, and device specifications. Limited dynamic range and lack of eye tracking were common limitations in lower-complexity devices. Pediatric validation and performance in early-stage disease were often suboptimal. Several VR-based perimetry systems demonstrate clinically acceptable validity compared to HFA, particularly in certain patient subgroups. However, broader validation, protocol standardization, and regulatory approval are essential for widespread clinical adoption. These devices may support more accessible visual field testing through telemedicine and decentralized care. Full article

Tyrosine kinase inhibitors (TKIs), either as single agents or in combination with other drugs, have become a gold standard in many oncological pathologies. The identification, analysis, and clinical management of their multiple and various systemic adverse events are a clear requirement and represent a true challenge in daily practice. For this narrative review, registration clinical trials that have led to the approval of certain TKI protocols in the setting of renal cell carcinoma (RCC) were identified via the latest version of the National Comprehensive Cancer Network (NCCN) kidney cancer guidelines. The following keywords were used: Axitinib, Cabozantinib, Lenvatinib, Pazopanib, Sorafenib, Sunitinib, and Tivozanib. RCC therapies have been proven to frequently induce oral symptoms and pathologies such as stomatitis, dysgeusia, xerostomia, osteonecrosis of the jaws, oral dysesthesia, geographic tongue, and dental and periodontal damage. The aim of this review is to emphasize the mechanisms of these common drug-induced buccodental toxicities associated with TKI therapies in RCC and to draft a general clinical management of these adverse events, in order to improve patients’ quality of life and treatment adherence. Full article

The Farnesoid-X-receptor (FXR) is a bile sensor involved in the regulation of bile acid homeostasis, fibrosis, inflammation, and metabolism. Obeticholic acid (OCA), a semisynthetic derivative of chenodeoxycholic acid (CDCA), initially named 6-ethyl-CDCA or INT-747, is the first in a class of FXR ligands that have been approved for clinical use for the treatment of patients with primary biliary cholangitis (PBC) who are unresponsive or intolerant to ursodeoxycholic acid. In this narrative review, we will examine the current status and future perspective of clinical use of OCA. Based on results from phase 2 and 3 clinical trials, OCA received a conditional market approval for its use as a second-line treatment for the management of PBC in 2016. However, concerns over drug (OCA)-induced liver injury (DILI), including hepatic decompensation in cirrhotic and non-cirrhotic PBC patients, have led to discontinuation of OCA commercialization in the EU, but not in North America and the UK, in 2024. Based on positive results from preclinical models, OCA has been investigated also for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). Results from phase 2 and 3 trials, however, have shown that while OCA reduces liver fibrosis, the beneficial effects on steatosis are marginal, thus preventing its clinical approval under the current regulatory guidelines. Here, we review potential applications of OCA in PBC patients in the context of a highly competitive therapeutic landscape, generated by the approval for clinical use of safer and effective second-line therapies, including PPARs agonists such as elafibranor and seladelapar and increased off-label use of fibrates. The current status of development of second-generation FXR agonists such as cilofexor, tropifexor, and vonafexor and their potential in the treatment of liver fibrosis in MASH will be discussed and compared to recently approved therapies, resmetirom, and semaglutide, a GLP-1 agonist. Finally, since some of the novel candidates for treating MASH, have shown limited efficacy on liver fibrosis, we suggest that development of combinatorial therapies based on FXR ligands and agents acting on different molecular targets might offer the opportunity for the repositioning of drug candidates whose development has been abandoned for insufficient efficacy, minimizing/recovering costs linked to drug development. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the most prevalent liver diseases, affecting up to 40% of adults and strongly associated with obesity and metabolic dysfunction. Despite the lack of approved pharmacological treatments, dietary interventions with plant-based foods, including the Mediterranean diet (MED), rich in numerous bioactive compounds may offer benefits for metabolic health and hepatic function. However, the role of individual plant foods in MASLD management remains unclear. Objectives: This review investigates the effects of specific plant-based foods, consumed as part of the MED and Dietary Approaches to Stop Hypertension (DASHs) diet, on metabolic outcomes, including hepatic function, in MASLD patients alone or in combination with comorbidities such as obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). Methods: A systematic search was registered and conducted across nine databases to identify randomized controlled trials (RCTs) carried out in adults with MASLD and published between January 2020 and May 2025, following PRISMA guidelines. Results: Plant-based interventions including oranges, whole-grain products (WGPs), high-fiber buns (HFBs), beetroot juice (BJ), garlic, ginger, flaxseed, spirulina, rapeseed oil, sour tea, and green coffee extract (GCE) demonstrated mixed effects on metabolic and hepatic outcomes. GCE, flaxseed, and rapeseed oil improved anthropometric measures, while sour tea and ginger supported blood pressure control. WGPs, GCE, flaxseed, rapeseed oil, spirulina, ginger, and garlic were beneficial for glycemic regulation, whereas WGPs, HFBs, BJ, golden flaxseed, rapeseed oil, and garlic improved lipid profiles. Liver enzymes improved following consumption of WGPs, BJ, sour tea, flaxseed oil, and garlic, and hepatic steatosis was reduced after intake of oranges, WGPs, HFBs, BJ, flaxseed powder, rapeseed oil, and garlic powder. Conversely, a solely fruit-rich diet (FRD) had negative effects across all outcomes. Conclusions: Plant-based foods improved metabolic outcomes, with WGPs, HFBs, beetroot, oranges, sour tea, flaxseed oil, and garlic providing specific benefits for liver health. Further research is needed to validate these effects and ensure their safety in MASLD management. Full article

Background: Tirzepatide (Mounjaro or Zepbound), a dual GLP-1/GIP receptor agonist, is approved for type 2 diabetes and weight management. Despite its efficacy, real-world safety data remain limited. This study analyzed post-marketing adverse events (AEs) associated with tirzepatide using the FDA Adverse Event Reporting System (FAERS) to identify emerging safety concerns. Methods: FAERS reports from 2022 to Q1 2025 were analyzed. Disproportionality analyses (proportional reporting ratio [PRR], reporting odds ratio [ROR], empirical Bayes geometric mean [EBGM], and information component [IC]) were performed to detect safety signals. Reports were stratified by year, demographics, and AE type, focusing on cases in which tirzepatide was the primary suspect. Results: Among 65,974 reports, the majority originated from the U.S. (96%), with middle-aged females (40–59 years; 67%) most frequently affected. Incorrect dose administration was the top AE, increasing 8-fold from 1248 (2022) to 9800 (2024), with strong risk signals (ROR 22.15, 95% CI (20.75–23.65), and ROR 23.43, 95% CI (22.82–24.05), respectively, and PRR 16.80, 95% CI (15.74–17.93), and PRR 17.62, 95% CI (17.16–18.09), respectively). Other common AEs included injection-site reactions (e.g., pain [5273 cases in 2024]), gastrointestinal issues (nausea [3602 in 2024]), and off-label use. Class-related AEs (e.g., decreased appetite and blood glucose fluctuations) were also reported. Conclusions: Tirzepatide is associated with significant dosing errors, injection-site reactions, and gastrointestinal AEs in real-world use. The rising trend in reports underscores the need for enhanced provider and patient education, clearer dosing guidelines, and proactive monitoring. Further research is warranted to explore causative factors and optimize risk mitigation strategies. Full article

Peripartum depression (PPD) represents a significant public health concern, affecting 10–17% of women globally. Traditional monoaminergic treatments demonstrate limited efficacy and delayed onset of action. The glutamate–GABA imbalance hypothesis provides a novel theoretical framework for understanding depression pathophysiology and developing targeted therapeutic interventions. This review examines emerging pharmacotherapeutic approaches targeting glutamatergic and GABAergic neurotransmitter systems for PPD treatment. Search criteria targeted randomized clinical trials investigating GABA-A-positive allosteric modulators (brexanolone, zuranolone, and ganaxolone) and NMDA receptor antagonists (ketamine and esketamine) in PPD patients. Brexanolone was the first neurosteroid to receive FDA approval for PPD, while zuranolone also shows promise. Ketamine and esketamine are also associated with reduced PPD risk, particularly with perioperative administration during cesarean delivery, though benefits are predominantly short-term. These glutamate–GABA pathway modulators represent novel therapeutic alternatives with rapid onset profiles. Further investigation and research are needed to optimize dosing protocols and patient selection criteria and to establish long-term efficacy before PPD treatment guidelines can be drafted. Full article