Contextual determinants of guideline-based family support during end-of-life cancer care and subsequent bereavement care: A cross-sectional survey of registered nurses.

PURPOSE: In end-of-life cancer care, 10-20% of bereaved family members experience adverse mental health effects, including prolonged grief disorder. Despite great efforts, evidence-based recommendations to support their grieving process and well-being are often not successfully adopted into routine clinical care. This study identified facilitators and barriers using implementation science methodology. METHODS: 81 registered nurses working in cancer care from four hospitals and three home care services in Switzerland assessed their current family support practices in end-of-life care and bereavement care. They then assessed organisational attributes of their institution and their own individual characteristics and skills regarding literature-based factors of potential relevance. Facilitators and barriers to guideline-based family support were determined using fractional logistic regression. RESULTS: Service specialisation in palliative care, a culture that supports change, the availability of family support guidelines, billing/reimbursement of bereavement support services, and individual knowledge of family support and skill were systematically associated with higher adoption of guideline-based family support practices. Lack of privacy with families and insufficient training acted as significant barriers. CONCLUSIONS: While several potentially relevant factors have emerged in the literature, certain organisational and individual determinants actually empirically predict guideline-based family support according to nurses in end-of-life cancer care, with some determinants having much stronger implications than others. This provides crucial guidance for focussing quality improvement and implementation efforts through tailored strategies, especially with scarce resources. Furthermore, adoption is lower in bereavement care than in end-of-life care, suggesting a particular need for supportive organisational cultures including specific training and billing/reimbursement options.

Single cell transcriptome analysis of the THY-Tau22 mouse model of Alzheimer's disease reveals sex-dependent dysregulations.

Alzheimer's disease (AD) progression and pathology show pronounced sex differences, but the factors driving these remain poorly understood. To gain insights into early AD-associated molecular changes and their sex dependency for tau pathology in the cortex, we performed single-cell RNA-seq in the THY-Tau22 AD mouse model. By examining cell type-specific and cell type-agnostic AD-related gene activity changes and their sex-dimorphism for individual genes, pathways and cellular sub-networks, we identified both statistically significant alterations and interpreted the upstream mechanisms controlling them. Our results confirm several significant sex-dependent alterations in gene activity in the THY-Tau22 model mice compared to controls, with more pronounced alterations in females. Both changes shared across multiple cell types and cell type-specific changes were observed. The differential genes showed significant over-representation of known AD-relevant processes, such as pathways associated with neuronal differentiation, programmed cell death and inflammatory responses. Regulatory network analysis of these genes revealed upstream regulators that modulate many of the downstream targets with sex-dependent changes. Most key regulators have been previously implicated in AD, such as Egr1, Klf4, Chchd2, complement system genes, and myelin-associated glycoproteins. Comparing with similar data from the Tg2576 AD mouse model and human AD patients, we identified multiple genes with consistent, cell type-specific and sex-dependent alterations across all three datasets. These shared changes were particularly evident in the expression of myelin-associated genes such as Mbp and Plp1 in oligodendrocytes. In summary, we observed significant cell type-specific transcriptomic changes in the THY-Tau22 mouse model, with a strong over-representation of known AD-associated genes and processes. These include both sex-neutral and sex-specific patterns, characterized by consistent shifts in upstream master regulators and downstream target genes. Collectively, these findings provide insights into mechanisms influencing sex-specific susceptibility to AD and reveal key regulatory proteins that could be targeted for developing treatments addressing sex-dependent AD pathology.

Daily Caffeine Consumption May Increase the Risk of Acute Kidney Injury Related to Platinum-Salt Chemotherapy in Thoracic Cancer Patients: A Translational Study.

Although their efficacy has been well-established in Oncology, the use of platinum salts remains limited due to the occurrence of acute kidney injury (AKI). Caffeine has been suggested as a potential pathophysiological actor of platinum-salt-induced AKI, through its hemodynamic effects. This work aims to study the association between caffeine consumption and the risk of platinum-salt-induced AKI, based on both clinical and experimental data. The clinical study involved a single-center prospective cohort study including all consecutive thoracic cancer patients receiving a first-line platinum-salt (cisplatin or carboplatin) chemotherapy between January 2017 and December 2018. The association between daily caffeine consumption (assessed by a validated auto-questionnaire) and the risk of platinum-salt induced AKI or death was estimated by cause-specific Cox proportional hazards models adjusted for several known confounders. Cellular viability, relative renal NGAL expression and/or BUN levels were assessed in models of renal tubular cells and mice co-exposed to cisplatin and increasing doses of caffeine. Overall, 108 patients were included (mean age 61.7 years, 65% men, 80% tobacco users), among whom 34 (31.5%) experienced a platinum-salt-induced AKI (67% Grade 1) over a 6-month median follow-up. The group of high-caffeine consumption (≥386 mg/day) had a two-fold higher hazard of AKI (adjusted HR [95% CI], 2.19 [1.05; 4.57]), without any significant association with mortality. These results are consistent with experimental data confirming enhanced cisplatin-related nephrotoxicity in the presence of increasing doses of caffeine, in both in vitro and in vivo models. Overall, this study suggests a potentially deleterious effect of high doses of daily caffeine consumption on the risk of platinum-salt-related AKI, in both clinical and experimental settings.

Effects of dignity therapy on psychological distress and wellbeing of palliative care patients and family caregivers - a randomized controlled study.

BACKGROUND: This study extended the original Dignity Therapy (DT) intervention by including partners and family caregivers (FCs) of terminally-ill cancer patients with the overall aim of evaluating whether DT can mitigate distress in both patients nearing the end of life and their FCs. METHODS: In this multicenter, randomized controlled trial (RCT), a total of 68 patients with life expectancy < 6 months and clinically-relevant stress levels (Hospital Anxiety Depression total score; HADStot ≥ 8) including their FCs were randomly assigned to DT, DT + (including their FCs), or standard palliative care (SPC) in a 1:1:1 ratio. Study participants were asked to complete a set of questionnaires pre- and post-intervention. RESULTS: The coalesced group (DT and DT +) revealed a significant increase in patients' perceived quality of life (FACIT-Pal-14) following the intervention (mean difference 6.15, SD = 1.86, p < 0.01). We found a statistically significant group-by-time interaction effect: while the HADStot of patients in the intervention group remained stable over the pre-post period, the control group's HADStot increased (F = 4.33, df = 1, 82.9; p < 0.05), indicating a protective effect of DT. Most patients and their FCs found DT useful and would recommend it to other individuals in their situation. CONCLUSIONS: The DT intervention has been well-received and shows the potential to increase HRQoL and prevent further mental health deterioration, illness burden and suffering in terminally-ill patients. The DT intervention holds the potential to serve as a valuable tool for facilitating end-of-life conversations among terminally-ill patients and their FCs. However, the implementation of DT within the framework of a RCT in a palliative care setting poses significant challenges. We suggest a slightly modified and less resource-intensive version of DT that is to provide the DT inventory to FCs of terminally-ill patients, empowering them to ask the questions that matter most to them over their loved one's final days. TRIAL REGISTRATION: This study was registered with Clinical Trial Registry (ClinicalTrials.gov -Protocol Record NCT02646527; date of registration: 04/01/2016). The CONSORT 2010 guidelines were used for properly reporting how the randomized trial was conducted.

The Psychoneuroimmunological Model of Moral Distress and Health in Healthcare Workers: Toward Individual and System-Level Solutions.

Healthcare is presently experiencing a global workforce crisis, marked by the inability of hospitals to retain qualified healthcare workers. Indeed, poor working conditions and staff shortages have contributed to structural collapse and placed a heavy toll on healthcare workers' (HCWs) well-being, with many suffering from stress, exhaustion, demoralization, and burnout. An additional factor driving qualified HCWs away is the repeated experience of moral distress, or the inability to act according to internally held moral values and perceived ethical obligations due to internal and external constraints. Despite general awareness of this crisis, we currently lack an organized understanding of how stress leads to poor health, wellbeing, and performance in healthcare workers. To address this critical issue, we first review the literature on moral distress, stress, and health in HCWs. Second, we summarize the biobehavioral pathways linking occupational and interpersonal stressors to health in this population, focusing on neuroendocrine, immune, genetic, and epigenetic processes. Third, we propose a novel Psychoneuroimmunological Model of Moral Distress and Health in HCWs based on this literature. Finally, we discuss evidence-based individual- and system-level interventions for preventing stress and promoting resilience at work. Throughout this review, we underscore that stress levels in HCWs are a major public health concern, and that a combination of system-level and individual-level interventions are necessary to address preventable health care harm and foster resilience in this population, including new health policies, mental health initiatives, and additional translational research.

End-of-life and bereavement support to families in cancer care: a cross-sectional survey with bereaved family members.

BACKGROUND: Losing a close other to cancer is an incisive experience that occurs after a long course of illness and intense family caregiving. Despite an evident need for family engagement and support and guidance on this, patients and family members may not receive the attention and support they need when a family unit is experiencing a disruption by death. A clear understanding of the quality of care that is currently provided and its ability to address family needs is necessary to improve end-of-life and bereavement support to families affected by cancer. The purpose of this study is to investigate the quality of support of end-of-life and bereavement care to families, their (un)met needs, grief experiences, and self-perceived health outcomes. METHODS: A multi-center, cross-sectional observational survey study with family members (n = 35) whose close other died of cancer in a health institution or their own home in German-speaking Switzerland. RESULTS: Bereaved family members were mostly satisfied with end-of-life care. Information on the grief process and services, and acknowledgment of their grief was experienced as helpful. Most coped with their grief drawing on family resources and exhibited resilience, but they reported unmet needs in relation to family togetherness and caregiving. CONCLUSION: This study with a small number of family members indicates that support provided to families across settings and illness trajectories is perceived as helpful, with specific needs related to family support. The findings suggest that improvements should focus on ensuring care that addresses the family as a unit and enables togetherness, mutual reflection, meaningful relationships, preparedness for death, resilience, and benefit-finding. PROTOCOL REGISTRATION: https://osf.io/j4kfh .

Acceptance of Digital Health Technologies in Palliative Care Patients.

Background: Digital health technologies have potential to transform palliative care (PC) services. The global aging population poses unique challenges for PC, which digital health technologies may help overcome. Evaluation of attitudes and perceptions combined with quantification of prior use habits favor an understanding of psychological barriers to PC patient acceptance of digital health technologies including artificial intelligence (AI). Objectives: We aimed to evaluate the attitudes and perceptions of PC patients regarding a broad range of digital health technologies used in their routine monitoring and treatment and identify barriers to use. Methods: We used a 39-item questionnaire to evaluate acceptance and use of smartphone-based electronic patient report outcome measures, wearables, AI, data privacy, and virtual reality (VR) in 29 female and male PC inpatients. Results: A majority of patients indicated an interest in (69.0%) and positive attitude toward (75.9%) digital health technologies. Nearly all (93.1%) patients believe that digital health technologies will become more important in medicine in the future. Most patients would consider using their smartphone (79.3%) or wearable (69.0%) more often for their health. The most feasible technologies were smartphones, wearables, and VR. Barriers to acceptance included unfamiliarity, data security, errors in data interpretation, and loss of personal interaction through AI. Conclusion: In this patient survey, acceptance of new technologies in a PC patient population was high, encouraging its use also at the end-of-life.

Outpatient Palliative Care Service Involvement: A Five-Year Experience from a Tertiary Hospital in Switzerland.

Background: The value of early integration of palliative care has been demonstrated increasingly for the past years in both oncological and nononcological diseases. Outpatient palliative care services might represent a feasible approach to implement supportive care in early disease. In this study, we aimed at evaluating which patients use and benefit from outpatient palliative care services, which symptoms are addressed most, and which support services are installed in this early phase of disease. Methods: We retrospectively analyzed the entire patient collective of a recently developed palliative care outpatient clinic within the leading university hospital in Switzerland for a period of five years. Sociodemographics, symptoms, and information on disease as well as patient-reported outcomes were retrieved from the electronic patient files. Demographic and clinical data were analyzed by descriptive statistics between groups and survival was analyzed by means of Kaplan-Meier estimates and log-rank test. Results: We report on 642 consultations of 363 patients between 2016 and 2020. Patients had a mean of 1.8 visits (range 1-10), with n = 340 patients (93.7%) of patients suffering from an oncological disease. Overall symptom load was high, with n = 401 (73.7%) of patient-reported outcomes reporting two or more symptoms. Distress levels of 5 or higher were reported in n = 78 (30.4%) of available patient-reported outcomes. Independent of the origin of primary disease and the length of the disease trajectory, patients were referred to the palliative care service in median only four months before death. Conclusion: We identify high symptom load and distress in the outpatient palliative patient population. Patients benefitted from supportive medication, improvement of ambulatory support systems and advance care planning, and more than one-third of patients remained in follow-up, indicating a good acceptance of the service. Overcoming the overall late referral could, however, further increase the quality of life at earlier stages of disease.

Adoption of evidence-based end-of-life and bereavement support to families in cancer care: A contextual analysis study with health professionals.

AIMS: To investigate the level of adoption of evidence-based family engagement and support during end-of-life cancer care and subsequent bereavement and its contextual facilitators and barriers from health professionals' perspectives, and to explore differences between professional groups. DESIGN: Contextual analysis using an online cross-sectional survey. METHODS: This study was conducted in four Swiss hospitals and three home care oncology and palliative care services. Non-parametric testing was used to investigate the level of adoption and differences between nurses, physicians, occupational- and physiotherapists and psychosocial professionals (chaplains, onco-psychologists and social workers). The STROBE checklist for cross-sectional studies was followed. RESULTS: The majority of the 111 participating health professionals were nurses. Adoption was statistically significantly higher during end-of-life care than bereavement, with nurses and physicians reporting higher levels than the other professional groups. Guidance on end-of-life family care was available in about half of the cases, in contrast to a quarter for bereavement care. Self-perceived knowledge, skills and attitudes were moderate to high, with nurses and physicians reporting higher levels than others, except for general skills in working with families. Organisational structures were experienced as rather supportive, with the psychosocial group appraising the organisational context as significantly less conducive to fully implementing end-of-life and bereavement care than others, particularly during the end-of-life phase. CONCLUSION: Evidence-based family engagement and support were better adopted during end-of-life care than bereavement. Overall, nurses and physicians felt better enabled to care for families compared to other professional groups. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. PROTOCOL REGISTRATION: https://osf.io/j4kfh. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Implementation and quality improvement efforts should focus particularly on the bereavement phase and be tailored to professional groups. IMPACT: The findings show that evidence-based family engagement and support practices during end-of-life were rather well adopted in contrast to subsequent bereavement care, with nurses and physicians better enabled than other professionals to provide care. A better understanding of health professionals' contributions and roles in family care is important to build interprofessional capacity for evidence-based end-of-life and bereavement support. REPORTING METHOD: The STROBE checklist for reports of cross-sectional studies was followed (von Elm et al., 2007).

Characteristics and clinical challenges in patients with substance use disorder in palliative care-experience from a tertiary center in a high-income country.

BACKGROUND: Access to palliative care is often limited for challenging and vulnerable groups, including persons with substance use disorders. However, with optimized healthcare options and liberal substitution policies, this patient group is likely to increase over the upcoming years, and comorbidities will also influence the need for palliative support. Here, we aim at analyzing characteristics and specific challenges associated with substance use disorders (SUD) in palliative care. METHODS: We retrospectively reviewed all patients diagnosed with substance use disorder that were treated at our Competence Center Palliative Care within the University Hospital Zurich, Switzerland between 2015 and 2021. Patient characteristics, including age, gender, duration of hospitalization, as well as specific metrics like body mass index, distinct palliative care assessment scores, and in-hospital opioid consumption were retrieved from the electronic patient files. Demographics and clinical data were analyzed by descriptive statistics, and compared to those of a control group of palliative care patients without SUD. An opioid calculator was used to standardize opioid intake based on morphine equivalents for meaningful comparisons. RESULTS: The primary characteristics revealed that the majority of individuals were single (56%), had no children (83%), lived alone (39%), and were either unemployed or recipients of a disability pension (in total 50%). Nicotine (89%), opioids (67%), and alcohol (67%) were the most used substances. We identified various comorbidities including psychiatric illnesses alongside SUD (56%), hepatitis A, B, or C (33%), and HIV infection (17%). Patients with SUD were significantly younger (p < 0.5), predominantly male (p < 0.05), and reported a higher prevalence of pain (p < 0.5) compared to the standard cohort of palliative patients. Regarding the challenges most frequently reported by healthcare practitioners, non-compliance, multimorbidity, challenging communication, biographical trauma, lack of social support, and unstable housing situations played a key role. CONCLUSION: Patients with SUD represent a complex and vulnerable group dealing with multiple comorbidities that profoundly affect both their physical and psychological well-being. Understanding their unique characteristics is pivotal in providing precise and suitable palliative care.

Galectin-3 aggravates microglial activation and tau transmission in tauopathy.

Alzheimer's disease is characterized by the accumulation of amyloid-ß plaques, aggregation of hyperphosphorylated tau (pTau), and microglia activation. Galectin-3 (Gal3) is a ß-galactoside-binding protein that has been implicated in amyloid pathology. Its role in tauopathy remains enigmatic. Here, we showed that Gal3 was upregulated in the microglia of humans and mice with tauopathy. pTau triggered the release of Gal3 from human induced pluripotent stem cell-derived microglia in both its free and extracellular vesicular-associated (EV-associated) forms. Both forms of Gal3 increased the accumulation of pathogenic tau in recipient cells. Binding of Gal3 to pTau greatly enhanced tau fibrillation. Besides Gal3, pTau was sorted into EVs for transmission. Moreover, pTau markedly enhanced the number of EVs released by iMGL in a Gal3-dependent manner, suggesting a role of Gal3 in biogenesis of EVs. Single-cell RNA-Seq analysis of the hippocampus of a mouse model of tauopathy (THY-Tau22) revealed a group of pathogenic tau-evoked, Gal3-associated microglia with altered cellular machineries implicated in neurodegeneration, including enhanced immune and inflammatory responses. Genetic removal of Gal3 in THY-Tau22 mice suppressed microglia activation, reduced the level of pTau and synaptic loss in neurons, and rescued memory impairment. Collectively, Gal3 is a potential therapeutic target for tauopathy.

Glial reactivity and T cell infiltration in frontotemporal lobar degeneration with tau pathology.

Frontotemporal lobar degeneration with tau (FTLD-tau) is a group of tauopathies that underlie ∼50% of FTLD cases. Identification of genetic risk variants related to innate/adaptive immunity have highlighted a role for neuroinflammation and neuroimmune interactions in FTLD. Studies have shown microglial and astrocyte activation together with T cell infiltration in the brain of THY-Tau22 tauopathy mice. However, this remains to be confirmed in FTLD-tau patients. We conducted a detailed post-mortem study of FTLD-tau cases including 45 progressive supranuclear palsy with clinical frontotemporal dementia, 33 Pick's disease, 12 FTLD-MAPT and 52 control brains to characterize the link between phosphorylated tau (pTau) epitopes and the innate and adaptive immunity. Tau pathology was assessed in the cerebral cortex using antibodies directed against: Tau-2 (phosphorylated and unphosphorylated tau), AT8 (pSer202/pThr205), AT100 (pThr212/pSer214), CP13 (pSer202), PHF1 (pSer396/pSer404), pThr181 and pSer356. The immunophenotypes of microglia and astrocytes were assessed with phenotypic markers (Iba1, CD68, HLA-DR, CD64, CD32a, CD16 for microglia and GFAP, EAAT2, glutamine synthetase and ALDH1L1 for astrocytes). The adaptive immune response was explored via CD4+ and CD8+ T cell quantification and the neuroinflammatory environment was investigated via the expression of 30 inflammatory-related proteins using V-Plex Meso Scale Discovery. As expected, all pTau markers were increased in FTLD-tau cases compared to controls. pSer356 expression was greatest in FTLD-MAPT cases versus controls (P < 0.0001), whereas the expression of other markers was highest in Pick's disease. Progressive supranuclear palsy with frontotemporal dementia consistently had a lower pTau protein load compared to Pick's disease across tau epitopes. The only microglial marker increased in FTLD-tau was CD16 (P = 0.0292) and specifically in FTLD-MAPT cases (P = 0.0150). However, several associations were detected between pTau epitopes and microglia, supporting an interplay between them. GFAP expression was increased in FTLD-tau (P = 0.0345) with the highest expression in Pick's disease (P = 0.0019), while ALDH1L1 was unchanged. Markers of astrocyte glutamate cycling function were reduced in FTLD-tau (P = 0.0075; Pick's disease: P < 0.0400) implying astrocyte reactivity associated with a decreased glutamate cycling activity, which was further associated with pTau expression. Of the inflammatory proteins assessed in the brain, five chemokines were upregulated in Pick's disease cases (P < 0.0400), consistent with the recruitment of CD4+ (P = 0.0109) and CD8+ (P = 0.0014) T cells. Of note, the CD8+ T cell infiltration was associated with pTau epitopes and microglial and astrocytic markers. Our results highlight that FTLD-tau is associated with astrocyte reactivity, remarkably little activation of microglia, but involvement of adaptive immunity in the form of chemokine-driven recruitment of T lymphocytes.

Multi-Omics Data Integration Reveals Sex-Dependent Hippocampal Programming by Maternal High-Fat Diet during Lactation in Adult Mouse Offspring.

Early-life exposure to high-fat diets (HF) can program metabolic and cognitive alterations in adult offspring. Although the hippocampus plays a crucial role in memory and metabolic homeostasis, few studies have reported the impact of maternal HF on this structure. We assessed the effects of maternal HF during lactation on physiological, metabolic, and cognitive parameters in young adult offspring mice. To identify early-programming mechanisms in the hippocampus, we developed a multi-omics strategy in male and female offspring. Maternal HF induced a transient increased body weight at weaning, and a mild glucose intolerance only in 3-month-old male mice with no change in plasma metabolic parameters in adult male and female offspring. Behavioral alterations revealed by a Barnes maze test were observed both in 6-month-old male and female mice. The multi-omics strategy unveiled sex-specific transcriptomic and proteomic modifications in the hippocampus of adult offspring. These studies that were confirmed by regulon analysis show that, although genes whose expression was modified by maternal HF were different between sexes, the main pathways affected were similar with mitochondria and synapses as main hippocampal targets of maternal HF. The effects of maternal HF reported here may help to better characterize sex-dependent molecular pathways involved in cognitive disorders and neurodegenerative diseases.

[Symptom Control in Nephrological Palliative Care].

INTRODUCTION: Nephrology may have quite a lot in common with with palliative care. Examples of this are the conservative therapy of a terminal chronic kidney disease or dialysis termination. Nevertheless, palliative co-care of patients with chronic kidney disease still happens rather rarely. On the one hand, this might be due to lacking experience regarding the benefits and opportunities of incorporating palliative care in nephrology care, on the other hand, palliative care is often misunderstood as pure "end-of-life" care. By highlighting the whole spectrum of palliative care, we aim to promote these two disciplines in order to integrate palliative care services into the nephrological treatment concept at an early stage.

Socio-economic determinants for the place of last care: results from the acute palliative care unit of a large comprehensive cancer center in a high-income country in Europe.

BACKGROUND AND INTRODUCTION: The place of last care carries importance for patients at the end of life. It is influenced by the realities of the social welfare and healthcare systems, cultural aspects, and symptom burden. This study aims to investigate the place of care trajectories of patients admitted to an acute palliative care unit. MATERIALS AND METHODS: The medical records of all patients hospitalized on our acute palliative care unit in 2019 were assessed. Demographic, socio-economic and disease characteristics were recorded. Descriptive and inferential statistics were used to identify determinants for place of last care. RESULTS: A total of 377 patients were included in this study. Median age was 71 (IQR, 59-81) years. Of these patients, 56% (n = 210) were male. The majority of patients was Swiss (80%; n = 300); about 60% (n = 226) reported a Christian confession; and 77% had completed high school or tertiary education. Most patients (80%, n = 300) had a cancer diagnosis. The acute palliative care unit was the place of last care for 54% of patients. Gender, nationality, religion, health insurance, and highest level of completed education were no predictors for place of last care, yet previous outpatient palliative care involvement decreased the odds of dying in a hospital (OR, 0.301; 95% CI, 0.180-0.505; p-value < 0.001). CONCLUSION: More than half of patients admitted for end-of-life care died on the acute palliative care unit. While socio-economic factors did not determine place of last care, previous involvement of outpatient palliative care is a lever to facilitate dying at home.

Blood-brain crosstalk: the roles of neutrophils, platelets, and neutrophil extracellular traps in neuropathologies.

Systemic inflammation, neurovascular dysfunction, and coagulopathy often occur concurrently in neuropathologies. Neutrophils and platelets have crucial synergistic roles in thromboinflammation and are increasingly suspected as effector cells contributing to the pathogenesis of neuroinflammatory diseases. In this review, we summarize the roles of platelet-neutrophil interactions in triggering complex pathophysiological events affecting the brain that may lead to the disruption of brain barriers, infiltration of toxic factors into the parenchyma, and amplification of neuroinflammation through the formation of neutrophil extracellular traps (NETs). We highlight the clinical significance of thromboinflammation in neurological disorders and examine the contributions of damage-associated molecular patterns (DAMPs) derived from platelets and neutrophils. These DAMPs originate from both infectious and non-infectious risk factors and contribute to the activation of inflammasomes during brain disorders. Finally, we identify knowledge gaps in the molecular mechanisms underlying neurodegenerative disease pathogenesis and emphasize the potential of interventions targeting platelets and neutrophils to treat neuroinflammatory diseases.

Mortality during or shortly after curative-intent radio-(chemo-) therapy over the last decade at a large comprehensive cancer center.

Background and Introduction: Definitive surgical, oncological and radio-oncological treatment may result in significant morbidity and acute mortality. Mortality during or shortly after treatment in patients undergoing curative radio-(chemo)-therapy has not been studied systematically. We reviewed all curative radio-(chemo-)therapies at a large comprehensive cancer center over the last decade. Materials and Methods: The institutional record was screened for patients who received curative-intent radio-(chemo-)therapy and deceased during or within 30 days after radiotherapy. Curative therapy was defined as prescribed dosage of EQD2 ≥ 50 Gy for radiotherapy alone and EQD2 ≥ 40 Gy for radiochemotherapies. Data on demographics, disease and treatment were assembled and assessed. Results: Of 15,255 radiotherapy courses delivered at our center, 8,515 (56%) were performed with curative-intent. During or within 30 days after radio-(chemo-)therapy, 78 patients died (0.9% of all curative-intent courses). Median age of the deceased patients was 70 (IQR, 62-78) years, and 36% (28/78) were female. Median pre-therapeutic ECOG-PS was 1 (IQR, 0-2) and Charlson-Comorbidity-Index was 3+ (IQR, 2-3+). The most common primary malignancies were head and neck cancer (33/78; 42%) and central nervous system tumors (13/78; 17%). Peritherapeutic mortality varied by primary tumor, with the highest prevalence observed in head and neck and gastrointestinal cancer patients with 2.9% (33/1,144) and 2.4% (8/332), respectively. Among patients with known cause of death (34/78; 44%), tumor progression (12/34; 35%) and pulmonary complications/causes (11/34; 35%) were most common. On multivariable regression analysis, a worse ECOG-PS was associated with a relatively earlier peri-radiotherapeutic death (p = 0.014). Conclusion: Mortality during or within 30 days of curative-intent radio-(chemo-)therapy was low, yet highest for head and neck (2.9%) and gastrointestinal tumor (2.4%) patients. Reasons for these findings include rapid tumor progression in some cancers, good patient selection, with ECOG-PS being most useful and predictive for avoiding early mortality. Future research should help refine predictors for peri-RT mortality.

Evaluation of a newly developed flipped-classroom course on interprofessional practice in health care for medical students.

Interprofessional education is expected to promote collaborative practice and should therefore be included in health professionals' curricula. Reports on interprofessional curricular development and its evaluation are rare. We therefore undertook a comprehensive quantitative and qualitative evaluation of a new, mandatory course on interprofessional collaboration for medical students during their third year of the Bachelor of Medicine study programme. The newly developed and implemented course spans over six weeks and was designed in a hybrid, flipped-classroom format. It incorporates experience- and case-based learning as well as interactions with other health professionals. Each student completes an eLearning and a clinical workshadowing individually before attending the - due to the pandemic - virtual live lectures. To assess quality and usefulness of teaching-learning formats and course structure to learn about interprofessional collaboration and to develop interprofessional competencies and identity, a quantitative and qualitative evaluation was performed with more than 280 medical students and 26 nurse educators from teaching hospitals using online surveys (open & closed-ended format). Data were analyzed descriptively and using content analysis processes. Students appreciated the flipped-classroom concept, the real-world case-based learning scenarios with interprofessional lecturer teams, and the possibility of an experience-based learning opportunity in the clinical setting including interaction with students and professionals from other health professions. Interprofessional identity did not change during the course. Evaluation data showed that the course is a promising approach for teaching-learning interprofessional competencies to medical students. The evaluation revealed three factors that determined the success of this course, namely, a flipped-classroom concept, the individual workshadowing of medical students with another health professional, mainly nurses, and live sessions with interprofessional teaching-learning teams. The course structure and teaching-learning methods showed potential and could serve as a template for interprofessional course development in other institutions and on other course topics.

[End-of-Life Dreams and Visions]. / Traum- und Wachvisionen am Lebensende.

End-of-Life Dreams and Visions Abstract: End-of life dreams and visions (ELDVs) or so-called death bed phenomena are transcendent experiences at the end of life that can be visual, auditory and/or kinesthetic, and often include visions of (deceased) loved ones, close friends or perceptions of places, travels, bright lights, or music. ELDVs typically occur weeks to hours prior to death and may comfort the dying and prepare spiritually for the end of life. Such experiences are frequently reported by dying individuals, the prevalence varying between 30 and 80%, but in the clinical context ELDVs are usually neglected, but interpreted and treated as pathological changes in the brain that result in, and from, delirium. This article tries to enlighten the occurrence, the contents and meanings of ELDVs in dying persons as opposed to delirium and night dreams using findings from the literature and from clinical observations. Implications of these conclusions for palliative care and the therapeutic relevance of ELDVs when taking care of dying individuals and their loved ones will also be discussed.

Development of a tool for palliative care needs assessment and intervention: mixed methods research at a Swiss tertiary oncology clinic.

BACKGROUND: Palliative care interventions improve quality-of-life for advanced cancer patients and their caregivers. The frequency and quality of service provision could be improved by a clinical tool that helps oncology professionals to assess unmet needs for palliative care interventions and to structure the interventions delivered. This paper aims to answer the following research question: what do oncology professionals and cancer patients view as important elements in a clinical tool for assessing unmet palliative care needs? Based on the feedback from professionals and patients, we developed and refined an intervention-focused clinical tool for use in cancer care. METHODS: This study used a prospective convergent mixed methods design and was carried out at a single tertiary hospital in Switzerland. Healthcare professionals participated in focus groups (n=29) and a Delphi survey (n=73). Patients receiving palliative care were interviewed (n=17). Purposive sampling was used to achieve maximal variation in participant response. Inductive content analysis and descriptive statistics were used to analyze focus group discussions, open-ended survey questions and interview data. Descriptive statistics were used for analyzing quantitative survey items and interviewee characteristics. RESULTS: Focus groups and Delphi surveys showed that seven key palliative care interventions were important to oncology professionals. They also valued a tool that could be used by doctors, nurses, or other professionals. Participants did not agree about the best timepoint for assessment. Two versions of a pilot clinical tool were tested in patient interviews. Interviews highlighted the divergent patient needs that must be accommodated in clinical practice. Patients provided confirmation that a clinical tool would be helpful to them. CONCLUSIONS: This paper reports on research carried out to understand what elements are most important in a tool that helps oncology professionals to identify patients' unmet needs and provide tailored palliative care interventions. This study demonstrated that professionals and patients alike are interested in a clinical tool. Responses from oncology healthcare professionals helped to identify relevant palliative care interventions, and patients provided constructive input used in designing a tool for use in clinical interactions.