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This research examined the association between occupational fatigue and work absenteeism in 110 female assistant nurses of a high-complexity hospital in Chile. A sociodemographic questionnaire and the Checklist Individual Strength (CIS) scale were used. The results showed that the predominant absenteeism range was 11-29 days. The highest means of fatigue occurred in those with seniority above 2 years, with more than 10 patients in charge and an annual contract. No significant difference was observed between the fatigue means concerning absenteeism, but a significant association was observed between physical fatigue (p = 0.040, OR = 1.054) and service seniority (p = 0.001, OR = 1.084) with work absenteeism. Finally, we can conclude that physical fatigue and seniority in the clinical service are significant risk factors for the occurrence of absenteeism.

Background Navafenterol (AZD8871) is a dual-pharmacology muscarinic antagonist β 2− agonist (MABA) molecule in development for the treatment of chronic obstructive pulmonary disease (COPD). The pharmacodynamics, safety and tolerability of single doses of navafenterol were investigated in patients with moderate to severe COPD. Methods This was a randomized, five-way complete cross-over study. Patients received single doses of navafenterol 400 μg, navafenterol 1800 μg and placebo (all double-blind) and indacaterol 150 μg and tiotropium 18 μg (both open-label active comparators). The primary pharmacodynamic endpoint was change from baseline in trough forced expiratory volume in 1 s (FEV 1 ) on day 2. Safety and tolerability were monitored throughout. Results Thirty-eight patients were randomized and 28 (73.7%) completed the study. Navafenterol 400 μg and 1800 μg demonstrated statistically significant improvements vs placebo in change from baseline in trough FEV 1 (least squares mean [95% confidence interval]: 0.111 [0.059, 0.163] L and 0.210 [0.156, 0.264] L, respectively, both P  < .0001). The changes were significantly greater with navafenterol 1800 μg vs the active comparators (least squares mean treatment difference: 0.065–0.069 L, both P  < .05). The frequency of treatment-emergent adverse events was similar for placebo and the active comparators (range 34.4–37.5%), slightly higher for navafenterol 400 μg (52.9%), and lowest for navafenterol 1800 μg (22.6%). Conclusions Both doses of navafenterol demonstrated sustained bronchodilation over 24 h. Navafenterol was well tolerated and no safety concerns were raised. Trial registry ClinicalTrials.gov ; No.: NCT02573155 ; URL: www.clinicaltrials.gov . Registered 9th October, 2015.

Wnt signaling is one of the key oncogenic pathways in multiple cancers, and targeting this pathway is an attractive therapeutic approach. However, therapeutic success has been limited because of the lack of therapeutic agents for targets in the Wnt pathway and the lack of a defined patient population that would be sensitive to a Wnt inhibitor. We developed a screen for small molecules that block Wnt secretion. This effort led to the discovery of LGK974, a potent and specific small-molecule Porcupine (PORCN) inhibitor. PORCN is a membrane-bound O-acyltransferase that is required for and dedicated to palmitoylation of Wnt ligands, a necessary step in the processing of Wnt ligand secretion. We show that LGK974 potently inhibits Wnt signaling in vitro and in vivo, including reduction of the Wnt-dependent LRP6 phosphorylation and the expression of Wnt target genes, such as AXIN2 . LGK974 is potent and efficacious in multiple tumor models at well-tolerated doses in vivo, including murine and rat mechanistic breast cancer models driven by MMTV–Wnt1 and a human head and neck squamous cell carcinoma model (HN30). We also show that head and neck cancer cell lines with loss-of-function mutations in the Notch signaling pathway have a high response rate to LGK974. Together, these findings provide both a strategy and tools for targeting Wnt-driven cancers through the inhibition of PORCN.

Background Navafenterol (AZD8871) is an inhaled long-acting dual-pharmacology muscarinic antagonist/β 2 -adrenoceptor agonist (MABA) in development for the treatment of obstructive airways diseases. The safety, tolerability, pharmacodynamics, and pharmacokinetics of navafenterol were investigated in patients with mild asthma. Methods This was a randomised, single-blind, placebo-controlled, single-ascending-dose study. Patients were randomly assigned to one of two cohorts which evaluated escalating doses of navafenterol (50–2100 μg) in an alternating manner over three treatment periods. The primary pharmacodynamic endpoint was the change from pre-dose baseline in trough forced expiratory volume in 1 s (FEV 1 ) for each treatment period. Results Sixteen patients were randomised; 15 completed treatment. Data from all 16 patients were analysed. The maximum tolerated dose was not identified, and all doses of navafenterol were well tolerated. The most frequently reported treatment-emergent adverse events (TEAEs) were headache ( n  = 10, 62.5%) and nasopharyngitis ( n  = 7, 43.8%). No TEAEs were serious, fatal, or led to discontinuation, and no dose dependency was identified. Navafenterol demonstrated a dose-ordered bronchodilatory response with a rapid onset of action (within 5 min post-dose). Doses ≥200 μg resulted in improvements in trough FEV 1 (mean change from baseline range 0.186–0.463 L) with sustained bronchodilation for 24–36 h. Plasma concentrations increased in a dose-proportional manner, peaking ~ 1 h post-dose, with a derived terminal elimination half-life of 15.96–23.10 h. Conclusions In this study navafenterol was generally well tolerated with a rapid onset of action which was sustained over 36 h. Trial registration ClinicalTrials.gov; No.: NCT02573155

Summary Sorafenib is an orally administered multikinase inhibitor that exhibits antiangiogenic and antitumor activity. Few investigators have been able to correlate cumulative sorafenib dose or total exposure to pharmacodynamic effects. This discrepancy may be in part due to poorly understood protein binding characteristics. Since unbound drug concentrations are believed to be more relevant to pharmacological and toxicological responses than total drug, an equilibrium dialysis method using 96-well microdialysis plates was optimized and validated for determining the fraction unbound (F u ) sorafenib in human plasma and in isolated protein solutions. Unbound sorafenib concentrations were determined in cancer patients receiving the drug orally at a dose of 400 mg and 600 mg twice daily. Sorafenib was extensively bound with mean F u value of 0.3% in both non-cancer and cancer patient’s plasma. The binding in plasma was concentration independent, indicating a low-affinity, possibly nonspecific and nonsaturable process. In isolated protein solutions, 99.8% and 79.3% of sorafenib was bound to human serum albumin (HSA) (4 g/dL) and α 1 -acid glycoprotein (AAG) (0.1 g/dL) with binding constants of 1.24 × 10 6  M −1 and 1.40 × 10 5  M −1 , respectively. In cancer patients receiving sorafenib, unbound sorafenib was not correlated with patient characteristics or laboratory values. In conclusion, sorafenib is highly protein bound in human plasma with a higher affinity towards albumin and limited free drug may be partly responsible for its borderline clinical activity.

Resumen Esta investigación ignifi la asociación entre la fatiga y el absentismo en el trabajo en 110 asistentes de enfermería de un hospital altamente complejo en Chile. Se ignifi un cuestionario sociodemográfico y la escala Check Strength Individual Strength. Los resultados mostraron que el ignific de absentismo predominante fue de 11 a 29 días. Los mayores promedios de fatiga se presentaron en los mayores de 2 años, con más de 10 pacientes en el consultorio y con contrato annual. No hubo diferencias significativas entre la fatiga media en relación con el absentismo, pero hubo una asociación ignificative entre la fatiga física (p = 0,040; OR = 1,054) y la antigüedad en el trabajo (p = 0,001; OR = 1,084) con el absentismo laboral. Finalmente, se concluye que la fatiga física y la antigüedad en el servicio clínico representaron un factor de riesgo significativo para el absentismo. Abstract This research examined the association between occupational fatigue and work absenteeism in 110 female assistant nurses of a high-complexity hospital in Chile. A sociodemographic questionnaire and the Checklist Individual Strength (CIS) scale were used. The results showed that the predominant absenteeism range was 11-29 days. The highest means of fatigue occurred in those with seniority above 2 years, with more than 10 patients in charge and an annual contract. No significant difference was observed between the fatigue means concerning absenteeism, but a significant association was observed between physical fatigue (p = 0.040, OR = 1.054) and service seniority (p = 0.001, OR = 1.084) with work absenteeism. Finally, we can conclude that physical fatigue and seniority in the clinical service are significant risk factors for the occurrence of absenteeism.

The retinal pigment epithelium (RPE) is an specialized epithelium lying in the interface between the neural retina and the choriocapillaris where it forms the outer blood-retinal barrier (BRB). The main functions of the RPE are the following: (1) transport of nutrients, ions, and water, (2) absorption of light and protection against photooxidation, (3) reisomerization of all-trans-retinal into 11-cis-retinal, which is crucial for the visual cycle, (4) phagocytosis of shed photoreceptor membranes, and (5) secretion of essential factors for the structural integrity of the retina. An overview of these functions will be given. Most of the research on the physiopathology of diabetic retinopathy has been focused on the impairment of the neuroretina and the breakdown of the inner BRB. By contrast, the effects of diabetes on the RPE and in particular on its secretory activity have received less attention. In this regard, new therapeutic strategies addressed to modulating RPE impairment are warranted.

Abstract OP 16: Exclusion and Discrimmination 2, B207 (FCSH), September 4, 2025, 13:30 - 14:30 Background Maternal outcomes for ethnic minority women facing social disadvantage are significantly poorer compared to those in more advantageous social positions. This disparity may be linked to fewer healthcare visits and increased barriers, such as discrimination. This study investigates the differences in everyday discrimination experienced by women at risk of preterm birth, from diverse ethnic backgrounds and levels of social deprivation and examines its impact on birth outcomes. Methods This secondary analysis utilised data from the POPPIE study, which included 333 participants from a diverse inner London sample. Aims 1) assess the impact of ethnicity and social deprivation on women’s experiences of discrimination during pregnancy; and 2) explore the relationship between discrimination and birth outcomes. The Everyday Discrimination Scale was employed. Propensity score matching was used to create comparable groups based on sociodemographic characteristics. Results The mean maternal age was 32 years (SD 5.4), with 38.1% identifying as non-White and 5.4% not fluent in English. Despite 45.6% holding high educational qualifications and 69% being in paid employment, 17% had a household income below £250 per week, primarily from areas of high social deprivation (69.3%). Significant differences in everyday discrimination scores were observed across ethnic groups, particularly among individuals from Black and Other ethnic backgrounds. Notably, race (p = 0.001) and skin colour (p = 0.013) were the primary reasons for reported discrimination, with over 70% of women from these groups experiencing considerable perceived discrimination. Conclusion This analysis highlights the intersection of deprivation, ethnicity, and experiences of discrimination. While no significant differences in maternal outcomes were found across ethnicities, the findings underscore the necessity for targeted healthcare services and information for ethnic minority pregnant women from lower socio-economic backgrounds. Further research is essential to explore these dynamics in larger samples and to incorporate routinely collected data on discrimination and stigma in maternal health research.

Background Disadvantaged populations (such as women from minority ethnic groups and those with social complexity) are at an increased risk of poor outcomes and experiences. Inequalities in health outcomes include preterm birth, maternal and perinatal morbidity and mortality, and poor-quality care. The impact of interventions is unclear for this population, in high-income countries (HIC). The review aimed to identify and evaluate the current evidence related to targeted health and social care service interventions in HICs which can improve health inequalities experienced by childbearing women and infants at disproportionate risk of poor outcomes and experiences. Methods Twelve databases searched for studies across all HICs, from any methodological design. The search concluded on 8/11/22. The inclusion criteria included interventions that targeted disadvantaged populations which provided a component of clinical care that differed from standard maternity care. Results Forty six index studies were included. Countries included Australia, Canada, Chile, Hong Kong, UK and USA. A narrative synthesis was undertaken, and results showed three intervention types: midwifery models of care, interdisciplinary care, and community-centred services. These intervention types have been delivered singularly but also in combination of each other demonstrating overlapping features. Overall, results show interventions had positive associations with primary (maternal, perinatal, and infant mortality) and secondary outcomes (experiences and satisfaction, antenatal care coverage, access to care, quality of care, mode of delivery, analgesia use in labour, preterm birth, low birth weight, breastfeeding, family planning, immunisations) however significance and impact vary. Midwifery models of care took an interpersonal and holistic approach as they focused on continuity of carer, home visiting, culturally and linguistically appropriate care and accessibility. Interdisciplinary care took a structural approach, to coordinate care for women requiring multi-agency health and social services. Community-centred services took a place-based approach with interventions that suited the need of its community and their norms. Conclusion Targeted interventions exist in HICs, but these vary according to the context and infrastructure of standard maternity care. Multi-interventional approaches could enhance a targeted approach for at risk populations, in particular combining midwifery models of care with community-centred approaches, to enhance accessibility, earlier engagement, and increased attendance. Trial registration PROSPERO Registration number: CRD42020218357.

Humanitarian Logistics (HL) is comprised of processes and involved systems in the mobilization of people, resources, and knowledge to help affected communities when they are faced with natural disasters. In this study, the Reference Task Model (RTM) provides an overview of these processes and supports Business Process Management (BPM). This article aims to evaluate from a proposed framework the selection of suppliers to guarantee indispensable material resources in the fastest way. We apply a BPM procedure to support the supplier selection process following a flood disaster. We describe each of the stages that make up the proposal of the BPM life cycle applied to the HL. We employ some tools as Balanced Scorecard (BSC) to achieve consensus on objectives, indicators, targets, and actions to be defined for a disaster situation. For balancing the allocation of supplies, the network flow problem is adapted for the quantitative model. That model contains the variables of time, demand, and capacity, and includes the set of adequate suppliers. For the application, we describe a flood disaster case study from a state located in southern Brazil. The main results of the application of the proposed framework are obtained from an optimized holistic view; they represent the selection of suppliers of humanitarian items and consider delivery times, resources, and deprivation costs. One contribution of the proposed framework is the ease of its implementation from process-based technologies and its emphasis on being strategy focused. Further, it concentrates experiences and good practices from humanitarian organizations.