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Mojtaba Vaismoradi,1 Shazia Jamshed,2 Stefan Lorenzl,3,4 Piret Paal5 1Faculty of Nursing and Health Sciences, Nord University, Bodø, 8049, Norway; 2Clinical Pharmacy and Practice, Faculty of Pharmacy, University Sultan Zainal Abidin, Terengganu, 22200, Malaysia; 3Professorship for Palliative Care, Institute of Nursing Science and -Practice, Paracelsus Medical University, Salzburg, 5020, Austria; 4Department of Neurology, Klinikum Agatharied, Hausham, 83734, Germany; 5WHO Collaborating Centre at the Institute for Nursing Science and Practice, Paracelsus Medical University, Salzburg, A-5020, AustriaCorrespondence: Mojtaba VaismoradiFaculty of Nursing and Health Sciences, Nord University, Bodø, 8049, NorwayTel +47 75 51 78 13Email mojtaba.vaismoradi@nord.noAbstract: Older people with long-term mental health conditions who receive care in their own home are vulnerable to the inappropriate use of medications and polypharmacy given their underlying health conditions and comorbidities. Inappropriate use of pro re nata (PRN) medications in these older people can enhance their suffering and have negative consequences for their quality of life and well-being, leading to readmission to healthcare settings and the increased cost of health care. This narrative review on published international literature aims at improving our understanding of medicines management in home care and how to improve PRN medication use among older people with long-term health conditions in their own home. Accordingly, the improvement of PRN medicines management for these older people requires the development of an individualised care plan considering ‘reduction of older people’s dependence on PRN medications’, ‘empowerment of family caregivers’, and ‘support by healthcare professionals.’ PRN medication use should be reduced through deprescription and discontinuation strategies. Also, older people and their family caregivers should be encouraged to prioritize the use of non-pharmacologic methods to relieve physical and psychological problems. Besides the empowerment of family caregivers through role development, education and training about PRN medications, and involvement in decision-making, they need support by the multidisciplinary network in terms of supervision, monitoring, and home visits.Keywords: family caregiver, home care, medication, medicines management, mental health, older people, patient safety, pro re nata, PRN

Abstract Background Experiential learning holds high potential for medical students’ education in palliative care. At RWTH Aachen University in Germany, medical students can participate in the course “The Patient as Teacher” offering a one-to-one exchange with a terminally ill patient over a period of several weeks complemented with four supervision sessions and writing of a reflective essay. The course had run from 2005 to 2020 before it was paused due to the Covid-19 pandemic. This study aimed to assess the course’s value as a palliative care teaching tool by investigating students’ motivation and experiences over the years 2005–2020. Methods A stratified sample of 24 essays was taken from all submitted essays (n = 78), eight essays from the years 2005–2009, 2010–2014, and 2015–2020. Subsequently, a thematic analysis of the selected essays was conducted. Results The students felt motivated by the opportunity to gain more experience in palliative care, to improve their communication skills and to decrease insecurities in interaction with terminally ill patients. They learned about the patient’s biography and medical history, and encountered physical, psychological, social, and spiritual dimensions of living with a life-limiting disease. Moreover, they experienced relationship building and communication with a terminally ill patient outside their role as future doctors. Ultimately, they considered their participation as a beneficial experience on both a personal and professional level. Conclusions The course “The Patient as Teacher” presents a valuable tool for experiential learning in palliative care, which has elicited an unceasingly positive response among the students who participated over the years. It has facilitated medical students in overcoming insecurities in dealing with terminally ill patients and supported them in further developing their professional identity.

Abstract Bilirubin is one of the most frequently used laboratory values to monitor critically ill patients with cholestatic liver dysfunction. Besides bilirubin, toxic bile acids (TBAs), which may cause severe organ damage, are typically elevated. A correlation between both parameters seems plausible, but data are lacking. The aim was to investigate whether there is a correlation between bilirubin and TBAs in patients’ blood and whether a compareable reduction can be observed during the use of the adsorber CytoSorb (CS). As part of the Cyto-SOLVE study (NCT04913298), 16 critically ill patients with cholestatic liver dysfunction, bilirubin concentration > 10 mg/dl, continuous kidney replacement therapy and CS-application were investigated. Bilirubin and TBA concentrations were measured from arterial blood at defined time points (before start, after 6 and 12 h). Relative reduction (RR) was calculated using the formula $$\:\:{\boldsymbol{RR}}\:{\boldsymbol{\left(\%\right)}}=\frac{{\boldsymbol{concentration\left(pre-post\right)}}}{{\boldsymbol{concentration\left(pre\right)}}}*{\boldsymbol{100}}$$ . A moderate to high correlation between bilirubin and TBA concentration at all defined timepoints (rstart=0.64, p = 0.008; r6h = 0.85, p

Abstract Introduction The release of pro-inflammatory cytokines in critically ill patients with sepsis leads to endothelial dysfunction resulting in cardiocirculatory insufficiency. Their extracorporeal elimination using the cytokine adsorber CytoSorb® (CS) (adsorption of especially hydrophobic molecules 500 pg/ml), continuous kidney replacement therapy, and the application of CS. Various cytokines and chemokines were measured pre- and post-CS as well as in patients’ blood at predefined timepoints. Significant changes in the concentrations were detected with the Wilcoxon test with associated samples. Clearance of the adsorber (ml/min) was calculated with: $$blood\,flow*\frac{{concentration\, \left( {pre - post} \right)}}{{concentration\, \left( {pre} \right)}}.$$ b l o o d f l o w ∗ c o n c e n t r a t i o n p r e - p o s t c o n c e n t r a t i o n pre . Results Most of the inflammatory mediators showed a high initial extracorporeal clearance of 70–100 ml/min after CS installation, which dropped quickly to 10-30 ml/min after 6 h of treatment. No difference in clearance was observed between pro- and anti-inflammatory cytokines. Despite extracorporeal adsorption, a significant (p

Abstract The astrocyte-to-neuron lactate shuttle model entails that, upon glutamatergic neurotransmission, glycolytically derived pyruvate in astrocytes is mainly converted to lactate instead of being entirely catabolized in mitochondria. The mechanism of this metabolic rewiring and its occurrence in human brain are unclear. Here by using immunohistochemistry (4 brains) and imaging mass cytometry (8 brains) we show that astrocytes of the adult human neocortex and hippocampal formation express barely detectable amounts of mitochondrial proteins critical for performing oxidative phosphorylation (OXPHOS). These data are corroborated by queries of transcriptomes (107 brains) of neuronal versus non-neuronal cells fetched from the Allen Institute for Brain Science for genes coding for a much larger repertoire of entities contributing to OXPHOS, showing that human non-neuronal elements barely expressed mRNAs coding for such proteins. With less OXPHOS, human brain astrocytes are thus bound to produce more lactate to avoid interruption of glycolysis.

Abstract Concentrating solar power plants are a clean energy source capable of competitive electricity generation even during night time, as well as the production of carbon-neutral fuels, offering a complementary role alongside photovoltaic plants. In these power plants, thousands of mirrors (heliostats) redirect sunlight onto a receiver, potentially generating temperatures exceeding 1000°C. Practically, such efficient temperatures are never attained. Several unknown, yet operationally crucial parameters, e.g., misalignment in sun-tracking and surface deformations can cause dangerous temperature spikes, necessitating high safety margins. For competitive levelized cost of energy and large-scale deployment, in-situ error measurements are an essential, yet unattained factor. To tackle this, we introduce a differentiable ray tracing machine learning approach that can derive the irradiance distribution of heliostats in a data-driven manner from a small number of calibration images already collected in most solar towers. By applying gradient-based optimization and a learning non-uniform rational B-spline heliostat model, our approach is able to determine sub-millimeter imperfections in a real-world setting and predict heliostat-specific irradiance profiles, exceeding the precision of the state-of-the-art and establishing full automatization. The new optimization pipeline enables concurrent training of physical and data-driven models, representing a pioneering effort in unifying both paradigms for concentrating solar power plants and can be a blueprint for other domains.

Drainage is the most important single factor affecting mires globally but its effects vary depending on drainage type, climate and wetland ecosystem. Sixteen transects in fifteen drained raised bogs in the hemiboreal zone of Estonia were examined to determine the spatial effects of drainage on vegetation and environmental factors. We found that the effects of drainage along a hydrosequence depended on the drainage type; i.e., whether it took the form of a cutoff ditch intercepting surface and subsurface water flow around the perimeter of the bog massif, or the drainage ditch crossed the central part of the bog. Some drains of the latter type were still functioning whereas old hand-dug examples seemed to be derelict and inactive. For both of the active drainage types, maximum water levels stabilised within 25 m of the ditch but drawdown effects on minimum and average water levels extended to 450 m. The vegetation variables that were most sensitive to drainage were the number and the percentage of bog-specific species, the number of ground vegetation species, the total cover of Sphagnum species, and the height and canopy cover of trees. Trees were rare when the minimum water level was higher than -20 cm, and the number of bog-specific species increased rapidly as the minimum water level rose towards the surface from -90 cm. Total cover of the shrub layer decreased and total cover of Sphagnum species increased almost linearly with a rise of minimum water level up to 40 cm, whereas the total cover of field layer species stabilised when the minimum water level was at -100 cm. Total cover of Sphagnum species in the field layer increased over distances of up to 250–300 m from the drainage ditch and the percentage of bog-specific and fen-specific species stabilised 190–300 m from the ditches.

Abstract Background Rhabdomyolysis is a serious condition that can lead to acute kidney injury with the need of renal replacement therapy (RRT). The cytokine adsorber Cytosorb® (CS) can be used for extracorporeal myoglobin elimination in patients with rhabdomyolysis. However, data on adsorption capacity and saturation kinetics are still missing. Methods The prospective Cyto-SOLVE study (NCT04913298) included 20 intensive care unit patients with severe rhabdomyolysis (plasma myoglobin > 5000 ng/ml), RRT due to acute kidney injury and the use of CS for myoglobin elimination. Myoglobin and creatine kinase (CK) were measured in the patient´s blood and pre- and post-CS at defined time points (ten minutes, one, three, six, and twelve hours after initiation). We calculated Relative Change (RC, %) with: $$1 - \left( {concentration(pre - post)\,/\,concentration\left( {pre} \right)} \right)*100$$ . Myoglobin plasma clearances (ml/min) were calculated with: $$\left( {bloodflow*\left( {1 - hematocrit} \right)} \right)*\left( {concentration\left( {pre - post} \right)\,/\,concentration\left( {pre} \right)} \right)$$ Results There was a significant decrease of the myoglobin plasma concentration six hours after installation of CS (median (IQR) 56,894 ng/ml (11,544; 102,737 ng/ml) vs. 40,125 ng/ml (7879; 75,638 ng/ml) (p

Introduction & Purpose The restorative effect of physical activity in alpine environments on mental and physical health is well recognized. However, a risk of accidents and post-accident mental health problems is inherent to every sport. We aimed to characterize mental health in individuals following mountain sport accidents requiring professional medical management. Here we summarize the most important results of our study which has already been published (Salvotti et al., 2024). Methods Adult victims of mountain sport accidents treated at the hospital of the Medical University of Innsbruck (Austria) between 2018 and 2020 completed a cross-sectional survey at least six months following the admission (median 44 months, n = 307). Symptoms of post-traumatic stress disorder (PTSD, PCL-5), anxiety, depression, and somatization (PHQ), resilience (RS-13), sense of coherence (SOC-9L), post-traumatic growth (PTGI) and quality of life (EUROHIS-QOL), as well as sociodemographic and clinical information were obtained from an online survey and extracted from electronic health records. Mental health outcome patterns were investigated by semi-supervised medoid clustering and modeled by machine learning. Results Symptoms of PTSD were observed in 19% of participants. Three comparably sized subsets of participants were identified: a (1) neutral, (2) post-traumatic growth and (3) post-traumatic stress cluster. The post-traumatic stress cluster was characterized by high prevalence of symptoms of mental disorders, low resilience, low sense of coherence and low quality of life as well as by younger age, the highest frequency of pre-existing mental disorders and persisting physical health consequences of the accident. Individuals in this cluster self-reported a need for psychological or psychiatric support following the accident and more cautious behavior during mountain sports since the accident. Reliability of machine learning-based prediction of the cluster assignment based on 40 variables available during acute medical treatment of accident victims was limited. Discussion The findings demonstrate that symptoms of PTSD can occur following mountain sport accidents, which is significant considering that mountain sport athletes are typically perceived as physically and mentally exceptionally healthy individuals. The cross-sectional design of the study limits the ability to assess peri-traumatic mental health, which has been shown to be critical for identifying vulnerable patients in other populations (Schultebraucks et al., 2020). Our findings align with recent initiatives to implement peri-traumatic screening tools and enhance mental health support in trauma care (American College of Surgeons, 2022). Conclusion A subset of individuals show symptoms of mental health disorders including symptoms of PTSD when assessed at least 6 months after mountain sport accident. Since early identification of these vulnerable patients remains challenging, psychoeducational measures for all patients and low-threshold access to mental health support are key until the robust screening procedures for at risk individuals are available. References American College of Surgeons. (2022). Best practices guidelines: Screening and intervention for mental health disorders and substance use and misuse in the acute trauma patient. https://www.facs.org/media/nrcj31ku/mental-health-guidelines.pdf Salvotti, H. V., Tymoszuk, P., Ströhle, M., Paal, P., Brugger, H., Faulhaber, M., Kugler, N., Beck, T., Sperner-Unterweger, B., & Hüfner, K. (2024). Three distinct patterns of mental health response following accidents in mountain sports: A follow-up study of individuals treated at a tertiary trauma center. European Archives of Psychiatry and Clinical Neuroscience, 274, 1289-1310. https://doi.org/10.1007/s00406-024-01807-x Schultebraucks, K., Shalev, A. Y., Michopoulos, V., Grudzen, C. R., Shin, S. M., Stevens, J. S., Maples-Keller, J. L., Jovanovic, T., Bonanno, G. A., Rothbaum, B. O., Marmar, C. R., Nemeroff, C. B., Ressler, K. J., & Galatzer-Levy, I. R. (2020). A validated predictive algorithm of post-traumatic stress course following emergency department admission after a traumatic stressor. Nature medicine, 26(7), 1084–1088. https://doi.org/10.1038/s41591-020-0951-z

Abstract Background Therapeutic drug monitoring (TDM) of anti-infectives such as linezolid is routinely performed in blood of intensive care unit (ICU) patients to optimize target attainment. However, the concentration at the site of infection is considered more important for a successful therapy. Until now, bronchoalveolar lavage (BAL) is the gold standard to measure intrapulmonary concentrations of anti-infective agents. However, it is an invasive method and unsuitable for regular TDM. The aim of this proof-of-concept study was to investigate whether it is possible to reliably determine the intrapulmonary concentration of linezolid from endotracheal aspiration (ENTA). Methods Intubated ICU patients receiving 600 mg intravenous linezolid twice daily were examined in steady state. First, preliminary experiments were performed in six patients to investigate which patients are suitable for linezolid measurement in ENTA. In a second step, trough and peak linezolid concentrations of plasma and ENTA were determined in nine suitable patients. Results Linezolid can validly be detected in ENTA with viscous texture and > 0.5 mL volume. The mean (SD) linezolid trough concentration was 2.02 (1.27) mg/L in plasma and 1.60 (1.36) mg/L in ENTA, resulting in a median lung penetration rate of 104%. The mean (SD) peak concentration in plasma and ENTA was 10.77 (5.93) and 4.74 (2.66) mg/L. Conclusions Linezolid can validly be determined in ENTA with an adequate texture and volume. The penetration rate is comparable to already published BAL concentrations. This method might offer a simple and non-invasive method for TDM at the site of infection “lung”. Due to promising results of the feasibility study, comparison of ENTA and BAL in the same patient should be investigated in a further trial.

Abstract Background In recent years, the subspecialty of neuropalliative care has emerged with the goal of improving the quality of life of patients suffering from neurological disease, though gaps remain in neuropalliative care education and training. E-learning has been described as a way to deliver interactive and facilitated lower-cost learning to address global gaps in medical care. We describe here the development of a novel, international, hybrid, and asynchronous curriculum with both self-paced modules and class-based lectures on neuropalliative care topics designed for the neurologist interested in palliative care, the palliative care physician interested in caring for neurological patients, and any other physician or advanced care providers interested in neuropalliative care. Methods The course consisted of 12 modules, one per every four weeks, beginning July 2022. Each module is based on a case and relevant topics. Course content was divided into three streams (Neurology Basics, Palliative Care Basics, and Neuropalliative Care Essentials) of which two were optional and one was mandatory, and consisted of classroom sessions, webinars, and an in-person skills session. Evaluation of learners consisted of multiple choice questions and written assignments for each module. Evaluation of the course was based on semi-structured qualitative interviews conducted with both educator and learner, the latter of which will be published separately. Audio files were transcribed and underwent thematic analysis. For the discussion of the results, Khan’s e-learning framework was used. Results Ten of the 12 participating educators were interviewed. Of the educators, three identified as mid-career and seven as senior faculty, ranging from six to 33 years of experience. Nine of ten reported an academic affiliation and all reported association with a teaching hospital. Themes identified from the educators’ evaluations were: bridging the global gap, getting everybody on board, defining the educational scope, investing extensive hours of voluntary time and resources, benefiting within and beyond the curriculum, understanding the learner’s experience, creating a community of shared learning, adapting future teaching and learning strategies, and envisioning long term sustainability. Conclusions The first year of a novel, international, hybrid, and asynchronous neuropalliative care curriculum has been completed, and its educators have described both successes and avenues for improvement. Further research is planned to assess this curriculum from the learner perspective.

The geographical exchange of non-native species can be highly asymmetrical, with some world regions donating or receiving more species than others. Several hypotheses have been proposed to explain such asymmetries, including differences in propagule pressure, source species (invader) pools, environmental features in recipient regions, or biological traits of invaders. We quantified spatiotemporal patterns in the exchange of non-native insects between Europe, North America, and Australasia, and then tested possible explanations for these patterns based on regional trade (import values) and model estimates of invader pool sizes. Europe was the dominant donor of non-native insect species between the three regions, with most of this asymmetry arising prior to 1950. This could not be explained by differences in import values (1827–2014), nor were there substantial differences in the sizes of modelled invader pools. Based on additional evidence from literature, we propose that patterns of historical plant introductions may explain these asymmetries, but this possibility requires further study.

Abstract Background A minority of European countries have compulsory training in palliative care within all medical schools. The aim of the study was to examine palliative care education in Estonia. Methods We used the adapted version of the Palliative Education Assessment Tool (PEAT) to evaluate palliative care education at the University of Tartu, the only medical school in Estonia. The PEAT comprises of different palliative care domains and allows for assessing the curricula for palliative care education. Results 26 hours (h) of palliative care is taught within the basic medical curriculum, which is divided between 14 courses. Ethical issues (4 h, lecture and seminar) and basics of palliative care (2.5 h, lecture) are well covered however, pain and symptom management (12.5 h, lecture, seminar, workshop), psychosocial, spiritual aspects (5.5 h, seminar), and communication (1.5 h, lecture) teaching do not reach the recommended number of hours. Teamwork and self-reflection are not taught at all. Conclusions Increased time, more diverse teaching strategies and clear learning outcomes are required to enable the development of palliative care education in Estonia. The teaching and learning of palliative care is a process that requires constant development and collaboration.