Search Results (6,646)

Preventable medication harm in oncology is often driven by drug-related adverse events (AEs) that trigger order changes such as holds, dose reductions, delays, rechallenges, and enhanced monitoring. Much of the evidence needed to make these decisions lives in unstructured clinical texts, where large language models (LLMs), a type of artificial intelligence (AI), now offer extraction and reasoning capabilities. In this narrative review, we synthesize empirical studies evaluating LLMs and related NLP systems applied to clinical text for oncology AEs, focusing on three decision-linked tasks: (i) AE detection from clinical documentation, (ii) Common Terminology Criteria for Adverse Events (CTCAE) grade assignment, and (iii) grade-aligned actions. We also consider how these findings can inform pharmacist-facing recommendations for order-level safety. We conducted a narrative review of English-language studies indexed in PubMed, Ovid MEDLINE, and Embase. Eligible studies used LLMs on clinical narratives and/or authoritative guidance as model inputs or reference standards; non-text modalities and non-empirical articles were excluded. Nineteen studies met inclusion criteria. LLMs showed the potential to detect oncology AEs from routine notes and often outperformed diagnosis codes for surveillance and cohort construction. CTCAE grading was feasible but less stable than detection; performance improved when outputs were constrained to CTCAE terms/grades, temporally anchored, and aggregated at the patient level. Direct evaluation of grade-aligned actions was uncommon; most studies reported proxies (e.g., steroid initiation or drug discontinuation) rather than formal grade-to-action correctness. While prospective, real-world impact reporting remained sparse, several studies quantified scale advantages and time savings, supporting an initial role as high-recall triage with pharmacist adjudication. Overall, the evidence supports near-term, pharmacist-in-the-loop use of AI for AE surveillance and review, with CTCAE-structured, citation-backed outputs delivered into the pharmacist’s electronic health record order-verification workspace as reviewable artifacts. Future work must standardize reporting and CTCAE/version usage, and measure grade-to-action correctness prospectively, to advance toward order-level decision support. Full article

Background: Cefiderocol (CFD) is a novel cephalosporin targeting multidrug-resistant Gram-negative bacterial (GNB) infections. It mimics siderophores to enter into GNB through iron transport receptors. However, evidence on its use in Hospital at Home (HaH) and outpatient parenteral antibiotic therapy (OPAT) programs remains scarce. Objectives: The primary objective was to evaluate feasibility and efficacy of CFD in HaH setting. The secondary objective was to assess its safety. Methods: A retrospective, observational study was conducted across six Spanish centers between January 2023 and December 2024. Adult patients with documented GNB infections treated with CFD in HaH units were included. Demographic, clinical and microbiological data, treatment characteristics, and outcomes were collected. Statistical analysis was descriptive; no inferential or correlation tests were performed. Results: 27 patients were included; 70.4% were male, with a median age of 69 years. Most infections were nosocomial (65.4%), particularly skin and soft tissue (37%). Septic shock occurred in 14.8% of patients. Pseudomonas aeruginosa (66.7%) and Klebsiella pneumoniae (14.8%) were the most frequent pathogens involved, with Verona Integron-encoded metallo-B-lactamase (VIM, 50%) being the predominant resistance mechanism. CFD was used as a first-line therapy in 63% of cases and in combination with other antibiotics in 40.7%. Median treatment duration was 21.7 days. Administration was mainly via peripherally inserted central catheters (PICC, 33.3%) and electronic pumps (52%). Adverse effects occurred in 7.4% of patients, leading to discontinuation in one case. A total of 88.8% of patients achieved clinical success, with 7.7% recurrence within a month. Escalation of care occurred in 7.7% and 19.2% were readmitted within a month after HaH discharge. No infection-related deaths were reported. Conclusions: CFD is a feasible, safe, and effective treatment for difficult-to-treat GNB infections in HaH settings. Full article

Background: Nintedanib (NIN), an intracellular inhibitor of tyrosine kinases that inhibits processes fundamental to the progression of pulmonary fibrosis (PPF), is used in the treatment of patients with PPF associated with systemic sclerosis. During NIN therapy, adverse events lead to a permanent dose reduction and treatment discontinuation. Therapeutic drug monitoring (TDM) can be used to manage and optimize drug administration based on the measurement of drug concentrations. Therefore, TDM can be helpful in minimizing the impact of adverse events and help patients remain in therapy. The aim of this study was to develop and validate a new bioanalytical UPLC-MS/MS method enabling the determination of NIN and its active metabolite in the plasma of patients with PPF associated with systemic sclerosis. Methods: Sample preparation was carried out using protein precipitation with an extraction mixture: acetonitrile neutralized with 2 M sodium carbonate. Analytes and the internal standard (intedanib-d3) were monitored using mass spectrometry (MS) and positive-ion-mode electrospray ionization by MRM. Chromatographic analysis was performed on a Zorbax SB-C18 column kept at 40 °C using isocratic elution. The mobile phase contained 0.1% formic acid in water; acetonitrile (35:65 v/v) was pumped at a flow rate of 0.3 mL/min. The analysis time was 5 min. Results: The method was verified according to the EMA guidelines over a concentration range of 2.00–200.00 ng/mL. The correlation coefficients for the calibration curves were found to be 0.9991 and 0.9957 for NIN and its metabolite BIBF 1202, respectively. The within- and between-run precision and accuracy of LLOQ were evaluated for NIN and BIBF 1202 to be within RSD 2.96%, 4.53%, 5.51%, and 6.72% and in the ranges of 102.2–107.3%, 98.0–101.8%, 104.3–114.2%, and 99.1–104.9, respectively. The stability of the analytes in plasma after 4 h at 30 °C was found to be satisfactory, meeting the assumed bias criteria below 15%. Conclusions: The proposed method was successfully applied to analyze two active compounds—NIN and BIBF 1202—in plasma samples at two time points: trough (pre-dose concentration) and 2–3 h (maximum concentration) after the administration of NIN. Full article

Background: Azathioprine (AZA)-associated acute pancreatitis (AP) and gastrointestinal intolerance (GI-INT) are major causes of drug discontinuation in inflammatory bowel disease (IBD). This study compared HLA alleles, demographics, and clinical variables between AZA-AP and AZA-GI-INT. Methods: Data from five IBD centers included control (n = 88), AZA-AP (n = 44), and GI-INT (n = 44) groups. AP was defined by the Atlanta criteria, and GI-INT as acute dyspeptic symptoms related to AZA that resolved after withdrawal. Demographics, disease features, and HLA-DQA1/DRB1 alleles were assessed for associations. Results: Among 176 patients, female sex was more frequent in AZA-AP and GI-INT than controls (p = 0.018, p < 0.001). AZA-AP patients were older at diagnosis vs. controls (p = 0.016) but not vs. GI-INT (p = 0.15). Smoking and alcohol were more common in AZA-AP. The median onset of AP was four weeks, with 91% occurring within three months. GI-INT occurred rapidly, with a median of one day and a maximum of three days after the first dose. HLA-DQA1/DRB1 positivity was comparable in GI-INT and controls (9.2% vs. 14.8%, p = 0.42) but higher in AZA-AP (27.3% vs. 14.8%, p = 0.08). Regression identified female sex, smoking, alcohol, budesonide, and HLA-DQA1/DRB1 positivity (OR 3.01, 95% CI 1.004–9.058; p = 0.049) as independent risk factors for AZA-AP. Conclusions: AZA-AP, but not GI-INT, appears genetically influenced, with HLA-DQA1/DRB1 association extending across populations. In IBD, AZA-AP usually emerges within three months and is linked to female sex, smoking, alcohol, and budesonide. GI-INT typically develops within hours to three days of initiation. These findings support AZA-AP and GI-INT as distinct idiosyncratic entities shaped by genetic, metabolic, and sensitivity factors. Full article

Background: Switching stable liver transplant (LT) recipients from twice-daily immediate-release tacrolimus (IR-Tac) to once-daily MeltDose^® extended-release tacrolimus (LCPT) has been proven safe and well tolerated. Moreover, the switch has been associated with enhanced treatment adherence, improvement of tremors, and preserved renal function. Here, we hypothesized that switching to LCPT early after LT may enhance long-term patient outcomes significantly. Methods: This single-center, observational study investigated the long-term safety of LCPT in a large cohort of LT recipients (n = 100). Allograft function, emerging adverse events, the incidence of rejection reactions, renal function, lipid and glucose metabolism, and treatment adherence were assessed over 24 months. Results: In 56% of patients, the switch was conducted within 4 weeks post-transplantation. Adverse events occurred in 90% of patients during the 24-month follow-up, including gastrointestinal complications (28%), neurological symptoms (28%), skin disorders (26%), metabolic disorders (22%), and fatigue (18%). Seven patients (7%) developed renal insufficiency, and five patients (5%) developed renal failure. Three episodes of chronic graft rejection reactions (3%) and a single transplant failure (1%) were observed over 24 months. LCPT was discontinued in 10 patients. Liver and renal function markers, blood lipids (cholesterol and triglycerides), and glucose levels remained stable over the 24-month follow-up. However, 58% of LT recipients had one of their liver function markers elevated at baseline (i.e., before the switch), 28% had low glomerular filtration rate (GFR < 60 mL/min/1.73 m²), and 18% had high serum creatinine (>1.3 mg/dL). In these subgroups, the early switch to LCPT was associated with a significant decrease in liver enzymes (p < 0.001 for alanine transaminase; p = 0.032 for gamma-glutamyl transferase; and p < 0.001 for total bilirubin) and a significant decrease in serum creatinine levels (p < 0.001). Self-reported treatment adherence was good and consistent throughout the study. Conclusions: The early switch from IR-Tac to LCPT was safe and effective in our cohort and may be particularly beneficial for patients with suboptimal liver and renal function following LT. Full article

In this work, a high-order modal discontinuous Galerkin (dG) method is employed to solve the Euler equations using entropy variables. Entropy conservation and stability are ensured at the spatial semi-discrete level through entropy-conserving/stable numerical fluxes and the over-integration technique. For time integration, linearly implicit Rosenbrock-type Runge–Kutta schemes are used. However, since these schemes are not provably entropy-conserving/stable, their use to predict unsteady flows may lead to solutions that lack the desired entropy properties. To address this issue, a relaxation technique is applied to enforce entropy conservation or stability at the fully discrete level. The accuracy, conservation/stability properties and robustness of the fully-discrete scheme equipped with the relaxation technique are assessed through the following numerical experiments: (1) the isentropic vortex, (2) the Kelvin-Helmholtz instability, (3) the Taylor–Green vortex. Full article

On the road to developing more sustainable and cost-efficient carbon fibres (CFs), replacing the conventional polyacrylonitrile (PAN) precursor with polyethylene (PE) is a promising alternative. Yet most PE-CF studies focus on fibre properties at laboratory or pilot scale and largely overlook scalability—especially in melt-spinning, where precursor filament counts have typically been limited to 32–100, far below industrial CF tows (1000–48,000). This study addresses that gap by (i) modifying a staple-fibre melt-spinning line (MSFP) to directly produce a 10,000-filament PE precursor and (ii) demonstrating inline filament merging on an industrial yarn (IDY) plant at Institut für Textiltechnik (ITA) as a pragmatic scale-up route. Direct 10 k spinning proved technically feasible but did not meet convertibility targets owing to inhomogeneous extrusion and quench: the MSFP precursor showed 18.1 ± 2.0 µm filament diameter, 21.9 ± 3.8 cN/tex tenacity and 130.8 ± 40.8% elongation (total solid draw ratio 2.02). In contrast, the IDY route delivered a fine and uniform precursor with a 9.43 ± 0.02 µm filament diameter, 38.42 ± 0.43 cN/tex tenacity, 15.91 ± 0.76% elongation, and 15.32 ± 1.16% shrinkage at 120 °C (total solid draw ratio 4.55). After discontinuous sulfonation, TGA indicated superior cross-linking of the IDY precursor (≈15% mass loss at 400–600 °C) versus MSFP (≈18%). Inline merging doubled filament count inline and small-scale plying enabled a 6 k tow. Transferring the IDY precursor into continuous sulfonation and carbonisation yielded PE-based CF with a filament diameter < 8.5 µm, tensile strength up to 2.0 GPa, tensile modulus up to 170 GPa, and elongation at break up to 1.75%, without surface defects. The results establish a clear scale-up roadmap: prioritise homogeneous fine-filament extrusion at low throughputs, co-develop segmented quench, and use a stepwise strategy (1–2 k filaments → inline merging → ≥6 k) to enable industrially relevant, cost-effective PE-based CF production. Full article

We present a unified framework for modelling the term structure of interest rates using affine term structure models (ATSMs) with jumps and regime switches. The novelty lies in combining affine jump diffusion models with regime switching dynamics within a unified framework, allowing for state-dependent jump behaviour while preserving analytical tractability. This integration enables the model to simultaneously capture nonlinear market regimes and discontinuous movements in interest rates—features that traditional affine models or regime switching models alone cannot jointly represent. Estimation is carried out using the Unscented Kalman Filter (UKF) with the belief that it is capable of handling nonlinearity and therefore should estimate the non-Gaussian dynamics well. The yield curve fit demonstrates that both models fit our data well. RMSEs show that the regime switching affine jump diffusion (RS-AJD) model outperforms the affine jump diffusion (AJD) in-sample. Full article

A variety of aerospace trajectory optimization problems are subject to either discontinuities or constraints at intermediate times, which define multiple arcs with distinctive governing equations. This work addresses multi-arc optimal control problems, with special interest regarding aerospace trajectories, and specifically focuses on the multipoint corner conditions that belong to the complete set of necessary conditions for an extremal, in the context of a general formulation. This includes intermediate times and states in the objective functional, together with unknown time-independent parameters. This study shows that 16 cases can occur for the multipoint corner conditions and groups them into three classes. Explicit, closed-form solutions of the multipoint corner relations are identified in each class, if certain conditions are met. In an indirect solution approach, these explicit expressions can be employed sequentially, thus reducing the number of unknowns of multi-arc problems to the same number of single-arc optimal control problems. This is extremely useful in the presence of a large number of arcs. Two challenging aerospace trajectory optimization problems are analyzed as illustrative examples, i.e., (i) the minimum-fuel ascent path of a multistage launch vehicle and (ii) minimum-time low-thrust orbit transfers with eclipse constraints on the available thrust. Full article

The contemporary landscape is characterised by overlapping values and pressures, where ecosystem services and cultural spaces are used by diverse categories of users. In fragile contexts such as the Phlegraean Fields in Italy, the exponential growth of mass tourism has intensified the anthropogenic impacts, exacerbated by limited landscape awareness among local communities. Thus, walkability fosters direct exploration, while experiential transects provide a lens to read ecological, cultural, and perceptual layers of places. Together with digital storytelling, these approaches converge in a phygital approach that enriches physical experience without supplanting it. The study covered approximately 115 km of routes across five municipalities, combining road audits, an 11-item survey, participatory mapping, and ArcGIS StoryMaps. Results showed a structurally complex and functionally fragile mobility system: sidewalks are discontinuous, lighting insufficient, less than one quarter of the network is fully pedestrian, and cycling facilities are almost absent. At the same time, digital layers diversified routes and supported situated learning. By integrating geo-spatial analysis and phygital tools, the research demonstrates a replicable strategy to enhance the awareness and sustainable enjoyment of complex landscapes. The present research is part of the PNRR project Changes ‘PE5Changes_Spoke1-WP4-Historical Landscapes Traditions and Cultural Identities’. Full article

With advances in scientific foundations and engineering practice, segmented mirrors—a key architecture for realizing extremely large apertures and high-resolution imaging—have become foundational across space astronomy, ground-based telescopes, and advanced manufacturing. In recent years, interferometry, which leverages optical coherence and phase sensitivity, has become a powerful tool for inter-segment co-phasing. Its capabilities have advanced markedly owing to developments in multi-wavelength techniques, high-speed high-dynamic-range detectors, and instantaneous phase-shifting methods. Relative to non-interferometric sensing, interferometry directly encodes and unwraps phase. This enables a unified framework that combines millimeter-scale dynamic range with nanometer-level resolution throughout coarse acquisition, fine phasing, and in situ maintenance. This paper first outlines the degrees of freedom and error sources in segmented mirrors. It then reviews the configurations and acquisition strategies of shearing, Mach–Zehnder, Michelson, Fizeau, and PISTIL interferometers, and systematizes interferogram processing methods—such as phase-shifting, synthetic-wavelength techniques, and digital holography—for retrieving piston and tip/tilt. Accuracy of piston is λ/50–λ/100, and tip/tilt accuracy can reach the arcsecond level, with resolution at the nanometer scale. Finally, we discuss pathways to extend interferometric metrology from segmented mirrors to other discontinuous surfaces (e.g., segmented detectors, segmented gratings, microlens arrays) and outlines future research directions. Full article

The development of electronic textiles (e-textiles) has advanced significantly thanks to the integration of printing technologies such as flexography, which enables the efficient and reproducible production of conductive circuits on fabrics. This study evaluates the impact of different surface pretreatments (hydrophobic and oleophobic) on the electrical conductivity of flexographically printed circuits on a variety of polyester textile substrates. Key parameters such as grammage, fabric type and surface uniformity are analyzed using stereomicroscopy and profilometry techniques to characterize conductive ink distribution. The results demonstrate that oleophobic pretreatment is more effective at reducing the resulting electrical resistance, promoting better ink adhesion and distribution. Among the fabrics with the best results, those with a more regular and compact structure, such as 15 thread/cm and 666.7 dtex polyester taffeta, show homogeneous ink coverage and the lowest electrical resistance (∼0.5 Ω/cm) compared to more irregular fabrics with discontinuities and higher resistance. The results show that uniformity in ink distribution, assessed by profilometry and color analysis, directly correlates with low electrical resistance. It can be concluded that the combination of a regular and compact textile structure, an adequate surface pretreatment, and a printing direction of the circuit pattern aligned with the weft permits optimizing the conductivity and quality of e-textiles produced by flexography. Full article

Patients with diabetes and chronic kidney disease (CKD-DM) often have residual albuminuria despite pharmacological treatment. Finerenone targets mineralocorticoid overactivation, but real-world evidence remains limited. This study evaluated the impact of finerenone in a cohort of patients with CKD-DM. This was a real-life study including patients with CKD-DM and an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m², treated with finerenone, aged ≥ 18 years, and followed at the Nephrology Department of Vall d’Hebron Hospital. Clinical and laboratory data were collected at baseline and at 1, 3, and 6 months of treatment. Changes in albuminuria and eGFR were analyzed in patients who completed 6 months of follow-up. A total of 60 patients were included in the analysis; 39 (65%) were male, with a median age of 79 ± 10.12 years. Finerenone was initiated at 10 mg daily in 57 patients (95%), with 38.3% escalating to 20 mg after 1 month. After 6 months, the urinary albumin-to-creatinine ratio (UACR) decreased by 37.1% (p = 0.012, n = 34). Patients with an initial eGFR drop > 20% showed a greater UACR decrease of around 43% at 3 (p = 0.012) and 6 months (p = 0.013). A significant 9.5% decline in eGFR was observed at 1 month, followed by stabilization at 3 and 6 months. Finerenone was discontinued in 10% of the patients due to adverse events. Hyperkalemia occurred in 18.3% of the patients, but no hospitalizations for adverse events or heart failure were reported. In summary, finerenone induced a significant 37.1% reduction in albuminuria after 6 months of treatment. This reduction was more pronounced in patients who experienced an initial eGFR dip ≥ 20%. Finerenone was generally well tolerated and appears to be a promising therapeutic strategy for reducing albuminuria in this population. Full article

Background: Atezolizumab plus bevacizumab (Atezo + Bev) is the standard of care for treatment-naïve patients with unresectable hepatocellular carcinoma (uHCC). Proteinuria is a treatment-emergent adverse event that often leads to Bev interruption. However, the relationship between Bev-related proteinuria and renal dysfunction is unclear. We retrospectively investigated the impact of proteinuria after starting Atezo + Bev on renal function in patients with uHCC. Methods: We performed a single-arm retrospective study of patients with uHCC treated with Atezo + Bev between 25 September 2020 and 31 May 2022, at Kindai University Hospital, Japan. The impact of proteinuria on renal function during Atezo + Bev treatment was analyzed in terms of the correlation between changes in urine protein creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) relative to baseline. Results: We analyzed data from 100 patients (median age 74 years; range 41–89; 75% male). During Atezo + Bev treatment, the median (interquartile range) maximum increase from baseline in UPCR was 0.39 (0.08 to 2.05) and the median maximum decline from baseline in eGFR was −7.5 (−20.5 to −3.0) mL/min/1.73 m². The Pearson and Spearman correlation coefficients (95% confidence intervals) between these variables were −0.16 (−0.34 to 0.04) and −0.13 (−0.32 to 0.07), respectively. Conclusions: We found no correlation between the changes in UPCR and eGFR during Atezo + Bev treatment. Bev interruption criteria are based on the degree of proteinuria; however, our results suggest that proteinuria does not necessarily impair renal function. Physicians should consider the risk–benefit profile when deciding whether to discontinue Bev in patients who develop proteinuria during Atezo + Bev treatment. Full article

Background/Objectives: Inefficient postoperative handovers contribute to medical malpractice and care discontinuity by omitting critical patient information and compromising patient health. This study aimed to evaluate and compare the quality of postoperative nurse handovers in ORs, PACUs, ICUs, and wards across four hospitals in Jeddah, Saudi Arabia. Methods: A descriptive, cross-sectional, comparative study was conducted among postoperative care nurses across four hospitals in the second health cluster in Jeddah, Saudi Arabia. Data were collected through an online questionnaire to assess handover quality via a Handover Quality Rating Form and sociodemographic information. Data analysis was performed using SPSS v28. Results: Among the 521 nurse participants (84.1% female, M_age = 34.5 years), the overall postoperative handover quality was 76.8%, with handover conduct and quality scoring the highest (27.9 ± 4.8 and 17.7 ± 3.1, respectively). Female nurses demonstrated significantly higher performance in teamwork and handover circumstances, whereas older nurses demonstrated significantly better teamwork, handover conduct, and quality. Saudi and younger nurses experienced significantly higher handover circumstances. Nurses’ educational level and years of experience in the present ward were significantly correlated with handover circumstances, conduct, and quality. Handovers from the theater to recovery resulted in higher average circumstances than those from recovery to the ward. The study setting was significantly associated with handover quality. Conclusions: These findings highlight the importance of local evaluating the handover quality of nurses in various contexts, specifically considering the circumstances, conduct, and teamwork when planning implementation and developing standardized handover protocols for different departments, specialties, and healthcare settings. These results support the development of targeted training programs and unit-specific handover protocols. Full article