PRA Health Sciences is a contract research organization (CRO) with headquarters in Raleigh, North Carolina that was founded as the Anti-Inflammatory Drug Study Group in 1976, renamed PRA in 1982, as it expanded into other therapeutic areas besides inflammation.
Food safety remains a critical global challenge, particularly due to contamination by aflatoxins (AFs), highly toxic secondary metabolites produced primarily by Aspergillus flavus and A. parasiticus. This significant group of mycotoxins frequently contaminate staple food commodities, posing serious risks to public health, food security, and agricultural sustainability, thus the need for their detection in food. Conventional analytical methods, including chromatographic and immunochemical techniques, although highly accurate, are often time-consuming, resource-intensive, and dependent on sophisticated instrumentation and skilled personnel, thereby limiting their applicability in decentralized and resource-limited settings. Recent advances in detecting AFs in food matrices is nanoparticle-based, thus the focus in this systematic review. In this study, a systematic review that critically evaluates nanoparticle-based detection strategies for AFs in food, highlighting their potential to transform food safety monitoring was conducted in accordance with the Joanna Briggs Institute (JBI) guidelines. Data generated was subsequently reported following the Preferred Reporting Items for Systematic Reviews and PRISMA framework. Peer-reviewed articles published between January 1, 2010 and December 31, 2023 were systematically retrieved from multiple electronic databases. Study screening, eligibility assessment, and data extraction were independently performed using Covidence systematic review management software. A total of 38 studies met the inclusion criteria and were included in the qualitative synthesis. The findings demonstrate a strong predominance of gold nanoparticles (AuNPs), attributed to their high surface-to-volume ratio, tunable surface chemistry, and exceptional optical properties, which collectively enhance assay sensitivity and signal transduction in immunosensing platforms. Notably, gold-silica core-shell nanoparticle-based assays achieved the lowest reported limit of detection (LOD) for Aflatoxin B1 (AFB1) of 0.24 pg/mL. Other nanomaterials, including carbon-based nanostructures and polymeric nanoparticles, also exhibited robust analytical performance, with reported LOD ranging from 0.5 pg/mL to 2.7 ng/mL, depending on the food matrix, nanomaterial type, and assay design. Overall, this systematic review highlights key trends in nanoparticle applications for AF detection and underscores their potential for rapid, highly sensitive, and field-deployable food safety diagnostic testing. Despite substantial progress, critical challenges related to scalability, reproducibility, standardization, and regulatory approval remain. Addressing these barriers will be essential for translating nanotechnology-based AF detection platforms from laboratory research into routine food safety surveillance and regulatory practice.
Background:Chronic post-surgical pain (CPSP) is a frequent complication after thoracic and cardiothoracic surgery; however, reported risk factors remain heterogeneous and inconsistent. Objective:To map and synthesize the factors associated with CPSP after thoracic and cardiac surgery and to determine the strength of evidence supporting each predictor category. Methods:An exploratory review was conducted following PRISMA-ScR guidelines. Searches were performed in PubMed, Scopus, and Web of Science, identifying 20 eligible studies. A complementary qualitative synthesis was undertaken: statistically significant p-values (p < 0.05) were extracted, and predictors were categorized by evidence strength (strong, moderate, limited/inconsistent). Results:Severe acute postoperative pain during the first postoperative days emerged as the strongest and most reproducible predictor of CPSP across designs and populations. Psychological distress, particularly anxiety, depression, and catastrophizing, also showed strong and consistent associations. Moderate evidence supported the influence of young age, female sex, low BMI, and pre-existing chronic pain. Surgical determinants such as operative duration, minimally invasive approaches, tissue trauma, and postoperative complications showed variable associations, as did anesthetic factors, especially high intraoperative remifentanil doses. Evidence for single-dose S-ketamine and regional blocks was limited or inconsistent. Preliminary findings related to inflammatory cytokines, microRNA phenotypes, and geriatric prediction models suggest additional biological contributors but remain exploratory. Conclusion:CPSP after thoracic and cardiothoracic surgery results from interacting nociceptive, psychological, procedural, and biological factors. Although heterogeneity across studies requires cautious interpretation, this synthesis highlights early postoperative pain control and psychological vulnerability screening as priority strategies in perioperative care, and underscores the need for standardized, prospective, biomarker-informed research.
Ledaborbactam etzadroxil, the prodrug of the active β-lactamase inhibitor ledaborbactam, is being developed in combination with ceftibuten to treat serious infections caused by drug-resistant Enterobacterales. This study evaluated the safety and pharmacokinetics of ceftibuten in healthy adults at anticipated higher doses required, in combination with ledaborbactam etzadroxil, to treat Enterobacterales infections. Thirty-six participants (n = 12 per cohort [ceftibuten n = 9, placebo n = 3]) received a single oral dose of ceftibuten (400, 800, or 1,200 mg) or matched placebo on day 1. Following a one-day washout, the same participants received repeat oral doses of ceftibuten (400 mg once daily, 400 mg every 12 hours [q12h], or 400 mg q8h) for 10 days. Of the 36 participants, 25 (ceftibuten 67%, placebo 78%) reported 65 treatment-emergent adverse events (TEAEs). Nausea (22%), headache (15%), and fatigue (15%) were the most reported TEAEs among ceftibuten-treated participants. No participant experienced serious adverse events or discontinuations due to TEAEs. In both single- and multiple-dose cohorts, cis-ceftibuten isomer exposure was dose-proportional for areas under the curve (AUCs) but less than dose-proportional for maximum concentrations (Cmax). Low levels of cis-ceftibuten accumulation were observed at steady state, with accumulation ratios of 1.06, 1.09, and 1.24 for the 400 mg once daily, q12h, and q8h cohorts, respectively. Cis-ceftibuten and trans-ceftibuten recovery in urine was 47% and 6%, respectively, following a single dose of 1,200 mg.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04314206.
Introduction:In recent decades, improvements in diagnostic accuracy in medical cases have been minimal despite rapid advancements in technology. Moreover, in complex cases, diagnostic accuracy remains a significant challenge, often reflecting practices from the 18th and 19th centuries. This comprehensive narrative review explores how cognitive bias may act as a critical, yet neglected, factor contributing to the persistent diagnostic error rate. Methods:A narrative review of the literature was conducted through a search of the George Washington University library databases and Google Scholar to identify studies related to physician cognition, complex medical diagnosis, and cognitive error. Results:This review synthesizes existing literature to propose a theoretical framework explaining how cognitive error, clinician cognition, tolerance of uncertainty, and attachment theory interact to influence the formation of cognitive bias at the cost of diagnostic accuracy and efficiency. Discussion:It is not only necessary for clinicians to focus on a patient's words, symptoms, or data to improve diagnostic accuracy, but also for clinicians to relate to others' distress through their own attachment styles: technology's critical blind spot. Clinicians with insecure attachment styles may struggle with metacognition, exhibit lower cognitive flexibility, have reduced tolerance for uncertainty, experience lower thresholds for cognitive load, and rely more heavily on heuristics, leading to an increased likelihood of cognitive error during complex medical cases. This theory provides a foundation for further research into how attachment influences clinician decision-making and diagnostic performance while also highlighting how medical education may reinforce these patterns.
Ledaborbactam etzadroxil (LED-E), a novel oral prodrug that converts to the active β-lactamase inhibitor (BLI) ledaborbactam (LED), is being developed in combination with ceftibuten (CTB) to address a need for oral treatments against drug-resistant Enterobacterales infections. Two Phase 1 studies were conducted to (i) evaluate the safety and pharmacokinetics of single doses of LED-E 100 to 1000 mg and multiple doses of LED-E 75 to 500 mg every 8 h (q8h) for 10 days, (ii) assess potential drug interactions between CTB and LED, and (iii) evaluate safety and pharmacokinetics following multiple doses of LED-E 300 or 500 mg with CTB 400 mg or placebo q8h for 10 days. Treatment-emergent adverse events (TEAEs) were reported for 82% LED-E ± CTB (n = 109) and 78% placebo (n=27) participants, respectively. TEAEs of gastrointestinal disorders were reported for 28% of the LED-E ± CTB and 15% of placebo participants. Following single doses, LED-E AUCinf was less than 2% of LED exposures, demonstrating extensive conversion to active BLI. LED AUC increased dose proportionally following single LED doses and less than proportionally following multiple LED-E doses. After 10 days of q8h dosing, the LED terminal half-life in plasma was approximately 11 to 12 h. Steady-state urinary excretion of LED-E-derived material (comprised almost entirely of unchanged LED) was 84%. No clinically relevant CTB and LED PK interactions occurred with the CTB + LED-E combination. These results support further development of the CTB + LED-E combination for the treatment of complicated urinary tract infections caused by drug-resistant Enterobacterales.CLINICAL TRIALSThese studies are registered with ClinicalTrials.gov as NCT04243863 and NCT04877379.
