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Background: Magnet hospitals, a concept developed in the U.S., have been associated with improved nurse recruitment and retention, and better patient outcomes. Magnet principles may be useful to address workforce challenges in European hospitals, but they have not been implemented or evaluated on a large scale in the European hospital context., Objective: This study aims to explore the initial phase of implementing Magnet principles in 11 acute care hospitals in six European countries. The specific objectives of the study were to investigate the type of work that characterises the early phase of implementation and how implementation leaders engage with their context., Methods: A multinational qualitative study was conducted, with data from 23 semi-structured, one-to-one interviews with implementation leaders in 11 acute care hospitals in six European countries. Thematic analyses guided the analysis of data., Findings: Three themes of core work processes during the early phase of implementing Magnet principles in European hospitals were identified. The first theme, 'Creating space for Magnet', describes how work was directed towards creating both political and organisational space for the project. The second theme, 'Framing to fit: understanding and interpreting Magnet principles', describes the translational work to understand what the Magnet model entails and how it relates to the local hospital context. Finally, the third theme, 'Calibrating speed and dose', describes the strategic work of considering internal and external factors to adjust the process of implementation., Conclusions: The first phase of implementation was characterised by conceptual and relational work; translating the Magnet concepts, considering the fit into existing structures and practices and making space for Magnet in the local context. Understanding the local context played an important role in shaping and guiding the navigation of professional and organisational tensions. Hospitals employed diverse strategies to either emphasise or downplay the role of nurses and nursing to facilitate progress in the implementation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To determine the well-being of physicians and nurses in hospital practice in Europe, and to identify interventions that hold promise for reducing adverse clinician outcomes and improving patient safety., Design: Baseline cross-sectional survey of 2187 physicians and 6643 nurses practicing in 64 hospitals in six European countries participating in the EU-funded Magnet4Europe intervention to improve clinicians' well-being., Setting: Acute general hospitals with 150 or more beds in six European countries: Belgium, England, Germany, Ireland, Sweden and Norway., Participants: Physicians and nurses with direct patient contact working in adult medical and surgical inpatient units, including intensive care and emergency departments., Main Outcome Measures: Burnout, job dissatisfaction, physical and mental health, intent to leave job, quality of care and patient safety and interventions clinicians believe would improve their well-being., Results: Poor work/life balance (57% physicians, 40% nurses), intent to leave (29% physicians, 33% nurses) and high burnout (25% physicians, 26% nurses) were prevalent. Rates varied by hospitals within countries and between countries. Better work environments and staffing were associated with lower percentages of clinicians reporting unfavourable health indicators, quality of care and patient safety. The effect of a 1 IQR improvement in work environments was associated with 7.2% fewer physicians and 5.3% fewer nurses reporting high burnout, and 14.2% fewer physicians and 8.6% fewer nurses giving their hospital an unfavourable rating of quality of care. Improving nurse staffing levels (79% nurses) and reducing bureaucracy and red tape (44% physicians) were interventions clinicians reported would be most effective in improving their own well-being, whereas individual mental health interventions were less frequently prioritised., Conclusions: Burnout, mental health morbidities, job dissatisfaction and concerns about patient safety and care quality are prevalent among European hospital physicians and nurses. Interventions to improve hospital work environments and staffing are more important to clinicians than mental health interventions to improve personal resilience., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Healthcare literature suggests that leadership behavior has a profound impact on nurse work-related well-being. Yet, more research is needed to better conceptualize, measure, and analyse the concepts of leadership and well-being, and to understand the psychological mechanisms underlying this association. Combining Self-Determination and Job Demands-Resources theory, this study aims to investigate the association between engaging leadership and burnout and work engagement among nurses by focusing on two explanatory mechanisms: perceived job characteristics (job demands and resources) and intrinsic motivation., Methods: A cross-sectional survey of 1117 direct care nurses (response rate = 25%) from 13 general acute care hospitals in Belgium. Validated instruments were used to measure nurses' perceptions of engaging leadership, burnout, work engagement, intrinsic motivation and job demands and job resources. Structural equation modeling was performed to test the hypothesised model which assumed a serial mediation of job characteristics and intrinsic motivation in the relationship of engaging leadership with nurse work-related well-being., Results: Confirmatory factor analysis indicated a good fit of the measurement model. The findings offer support for the hypothesized model, indicating that engaging leadership is linked to enhanced well-being, as reflected in increased work engagement, and reduced burnout. The results further showed that this association is mediated by nurses' perceptions of job resources and intrinsic motivation. Notably, while job demands mediated the relationship between EL and nurses' well-being, the relationship became unsignificant when including intrinsic motivation as second mediator., Conclusions: Engaging leaders foster a favourable work environment for nursing staff which is not only beneficial for their work motivation but also for their work-related well-being. Engaging leadership and job resources are modifiable aspects of healthcare organisations. Interventions aimed at developing engaging leadership behaviours among nursing leaders and building job resources will help healthcare organisations to create favourable working conditions for their nurses., Trial Registration: The study described herein is funded under the European Union's Horizon 2020 Research and Innovation programme from 2020 to 2023 (Grant Agreement 848031). The protocol of Magnet4Europe is registered in the ISRCTN registry (ISRCTN10196901)., (© 2024. The Author(s).)

Background: Literature shows that the work environment is a main determinant of nurses' well-being and psychological strain; yet, the (psychological) mechanisms underlying this relationship remain understudied., Objective: This study explored the underlying (psychological) mechanisms (why) and boundary conditions (when) by which characteristics present in the clinical work environment influence nurses' well-being. We investigated the mediating role of intrinsic motivation in the relationship of job demands and job resources with burnout vs. work engagement. In addition, we examined if job resources strengthen the relationship of job demands with intrinsic motivation and burnout., Design: A cross-sectional survey study., Setting(s): General acute care hospitals in Belgium (n = 14)., Participants: Direct care nurses (n = 1729)., Methods: Data were collected by means of online questionnaires between October 2020 and July 2021. Study variables included burnout, work engagement, intrinsic motivation and a set of different job demands (workload, role conflicts, emotional demands, red tape) and job resources (performance feedback, autonomy, skill use, opportunity for growth, and value congruence). All variables were obtained using self-report measures. The central hypotheses were tested using structural equation modeling., Results: Job resources appeared to be a crucial factor for nurses' health showing positive associations with work motivation (β = 0.513) and work engagement (β = 0.462) and negative associations with burnout (β = -0.216). Job demands remained an essential factor that harms psychological health and is associated with increased burnout (β = 0.489). Our results confirmed that intrinsic motivation mediated the relationship of job resources with work engagement (β = 0.170) and burnout (β = -0.135). In addition, job resources moderated the relationship of job demands with burnout (β = -0.039). Against our expectations, we found no associations between job demands and intrinsic motivation or a moderation effect of job resources on the respective relationship., Conclusions: A highly demanding work environment can be a source of significant stress which may put nurses' health at severe risk. Nurses who perceive sufficient job resources such as feedback, autonomy and opportunities for growth and development, are likely to feel intrinsically motivated at work. In addition, it will foster their work engagement and prevent them from burning out, particularly when job demands are high., Registration: The study described herein is funded under the European Union's Horizon 2020 Research and Innovation program from 2020 to 2023 (Grant Agreement 848031). The protocol of Magnet4Europe is registered in the ISRCTN registry (ISRCTN10196901)., Tweetable Abstract: Providing nurses with sufficient resources will not only increase their motivation and engagement at work but also reduce their feelings of burnout., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To examine the prevalence, antecedents and consequences of physician care left undone in acute care hospitals., Design: A multicentre, multinational, cross-sectional survey. An 11-item scale measured physician reports of care left undone. Antecedent measures examined were work environment and perceived workload. Potential consequences examined included emotional exhaustion, job dissatisfaction and perceived quality of care. Generalized linear mixed models were estimated to quantify associations between physician care left undone and the theorized antecedents and consequences., Setting: 56 acute care hospitals in six European countries., Participants: 1 963 physicians providing direct patient care to adult in-patients., Results: Four in five (78.3 %) physicians left one or more care activities undone during their last shift. On average 3.1 (SD 1.0) of 11 activities were left undone. This varied between and within countries. A 10 % increase at the hospital level of physicians saying they have too much work to do, significantly increased the odds of one or more activities being left undone (OR 1.414, 95 % CI 1.268-1.578). Physicians' reports of care left undone were associated with increased odds of emotional exhaustion (OR 3.867, 95 %CI 2.683-5.575) and rating quality of medical care as poor or fair (OR 3.395, 95 % CI 2.215-5.204)., Conclusion: Physicians frequently report leaving some necessary care undone. A shortage of resources compromises physicians' ability to do their jobs, impacting the quality of care they deliver and their job satisfaction and well-being. Ensuring adequate healthcare personnel resources should be a top priority for hospitals., Competing Interests: Declaration of Competing Interest The authors declare they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Multiple myeloma (MM) is a highly refractory hematologic cancer. Targeted immunotherapy has shown promise in MM but remains hindered by the challenge of identifying specific yet broadly representative tumor markers. We analyzed 53 bone marrow (BM) aspirates from 41 MM patients using an unbiased, high-throughput pipeline for therapeutic target discovery via single-cell transcriptomic profiling, yielding 38 MM marker genes encoding cell-surface proteins and 15 encoding intracellular proteins. Of these, 20 candidate genes were highlighted that are not yet under clinical study, 11 of which were previously uncharacterized as therapeutic targets. The findings were cross-validated using bulk RNA sequencing, flow cytometry, and proteomic mass spectrometry of MM cell lines and patient BM, demonstrating high overall concordance across data types. Independent discovery using bulk RNA sequencing reiterated top candidates, further affirming the ability of single-cell transcriptomics to accurately capture marker expression despite limitations in sample size or sequencing depth. Target dynamics and heterogeneity were further examined using both transcriptomic and immuno-imaging methods. In summary, this study presents a robust and broadly applicable strategy for identifying tumor markers to better inform the development of targeted cancer therapy., Significance: Single-cell transcriptomic profiling and multiomic cross-validation to uncover therapeutic targets identifies 38 myeloma marker genes, including 11 transcribing surface proteins with previously uncharacterized potential for targeted antitumor therapy., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Tele-emergency physicians (TEPs) take an increasingly important role in the need-oriented provision of emergency patient care. To improve emergency medicine in rural areas, we set up the project 'Rural|Rescue', which uses TEPs to restructure professional rescue services using information and communication technologies (ICTs) in order to reduce the therapy-free interval. Successful implementation of ICTs relies on user acceptance and knowledge sharing behavior., Method: We conducted a factorial design with active knowledge transfer and technology acceptance as a function of work satisfaction (high vs. low), workload (high vs. low) and point in time (prior to vs. after digitalization). Data were collected via machine readable questionnaires issued to 755 persons (411 pre, 344 post), of which 304 or 40.3% of these persons responded (194 pre, 115 post)., Results: Technology acceptance was higher after the implementation of TEP for nurses but not for other professions, and it was higher when the workload was high. Regarding active communication and knowledge sharing, employees with low work satisfaction are more likely to share their digital knowledge as compared to employees with high work satisfaction. This is an effect of previous knowledge concerning digitalization: After implementing the new technology, work satisfaction increased for the more experienced employees, but not for the less experienced ones., Conclusion: Our research illustrates that employees' workload has an impact on the intention of using digital applications. The higher the workload, the more people are willing to use TEPs. Regarding active knowledge sharing, we see that employees with low work satisfaction are more likely to share their digital knowledge compared to employees with high work satisfaction. This might be attributed to the Dunning-Kruger effect. Highly knowledgeable employees initially feel uncertain about the change, which translates into temporarily lower work satisfaction. They feel the urge to fill even small knowledge gaps, which in return leads to higher work satisfaction. Those responsible need to acknowledge that digital change affects their employees' workflow and work satisfaction. During such times, employees need time and support to gather information and knowledge in order to cope with digitally changed tasks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hasebrook et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The increasing burden of mental distress reported by healthcare professionals is a matter of serious concern and there is a growing recognition of the role of the workplace in creating this problem. Magnet hospitals, a model shown to attract and retain staff in US research, creates positive work environments that aim to support the well-being of healthcare professionals., Methods and Analysis: Magnet4Europe is a cluster randomised controlled trial, with wait list controls, designed to evaluate the effects of organisational redesign, based on the Magnet model, on nurses' and physicians' well-being in general acute care hospitals, using a multicomponent implementation strategy. The study will be conducted in more than 60 general acute care hospitals in Belgium, England, Germany, Ireland, Norway and Sweden. The primary outcome is burnout among nurses and physicians, assessed in longitudinal surveys of nurses and physicians at participating hospitals. Additional data will be collected from them on perceived work environments, patient safety and patient quality of care and will be triangulated with data from medical records, including case mix-adjusted in-hospital mortality. The process of implementation will be evaluated using qualitative data from focus group and key informant interviews., Ethics and Dissemination: This study was approved by the Ethics Committee Research UZ/KU Leuven, Belgium; additionally, ethics approval is obtained in all other participating countries either through a central or decentral authority. Findings will be disseminated at conferences, through peer-reviewed manuscripts and via social media., Trial Registration Number: ISRCTN10196901., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

T-cell-based immunotherapy, such as CAR-T cells and bispecific T-cell engagers (BiTEs), has shown promising clinical outcomes in many cancers; however, these therapies have significant limitations, such as poor pharmacokinetics and the ability to target only one antigen on the cancer cells. In multiclonal diseases, these therapies confer the development of antigen-less clones, causing tumor escape and relapse. In this study, we developed nanoparticle-based bispecific T-cell engagers (nanoBiTEs), which are liposomes decorated with anti-CD3 monoclonal antibodies (mAbs) targeting T cells, and mAbs targeting the cancer antigen. We also developed a nanoparticle that targets multiple cancer antigens by conjugating multiple mAbs against multiple cancer antigens for T-cell engagement (nanoMuTEs). NanoBiTEs and nanoMuTEs have a long half-life of about 60 h, which enables once-a-week administration instead of continuous infusion, while maintaining efficacy in vitro and in vivo. NanoMuTEs targeting multiple cancer antigens showed greater efficacy in myeloma cells in vitro and in vivo, compared to nanoBiTEs targeting only one cancer antigen. Unlike nanoBiTEs, treatment with nanoMuTEs did not cause downregulation (or loss) of a single antigen, and prevented the development of antigen-less tumor escape. Our nanoparticle-based immuno-engaging technology provides a solution for the major limitations of current immunotherapy technologies., (© 2021. The Author(s).)

Background and Objective: Teleemergency doctors support ambulance cars at the emergency site by means of telemedicine. Currently, each district has its own teleemergency doctor office (decentralized solution). This paper analyses the advantages and disadvantages of a centralized solution where several teleemergency doctors work in parallel in one office to support the ambulances in more districts., Methods: The service of incoming calls from ambulances to the teleemergency doctor office can be modelled as a queuing system. Based on the data of the district of Vorpommern-Greifswald in the Northeast of Germany, we assume that arrivals and services are Markov chains. The model has parallel channels proportionate to the number of teleemergency doctors working simultaneously and the number of calls which one doctor can handle in parallel. We develop a cost function with variable, fixed and step-fixed costs., Results: For the district of Greifswald, the likelihood that an incoming call has to be put on hold because the teleemergency doctor is already fully occupied is negligible. Centralization of several districts with a higher number of ambulances in one teleemergency doctor office will increase the likelihood of overburdening and require more doctors working simultaneously. The cost of the teleemergency doctor office per ambulance serviced strongly declines with the number of districts cooperating., Discussion: The calculations indicate that centralization is feasible and cost-effective. Other advantages (e.g. improved quality, higher flexibility) and disadvantages (lack of knowledge of the location and infrastructure) of centralization are discussed., Conclusions: We recommend centralization of telemedical emergency services. However, the number of districts cooperating in one teleemergency doctor office should not be too high and the distance between the ambulance station and the telemedical station should not be too large.

Background: Over the past decade Smartphone-based activation (SBA) of Community First Responders (CFR) to out-of-hospital cardiac arrests (OHCA) has gained much attention and popularity throughout Europe. Various programmes have been established, and interestingly there are considerable differences in technology, responder spectrum and the degree of integration into the prehospital emergency services. It is unclear whether these dissimilarities affect outcome. This paper reviews the current state in five European countries, reveals similarities and controversies, and presents consensus statements generated in an international conference with the intention to support public decision making on future strategies for SBA of CFR., Methods: In a consensus conference a three-step approach was used: (i) presentation of current research from five European countries; (ii) workshops discussing evidence amongst the audience to generate consensus statements; (iii) anonymous real-time voting applying the modified RAND-UCLA Appropriateness method to adopt or reject the statements. The consensus panel aimed to represent all stakeholders involved in this topic., Results: While 21 of 25 generated statements gained approval, consensus was only found for 5 of them. One statement was rejected but without consensus. Members of the consensus conference confirmed that CFR save lives. They further acknowledged the crucial role of emergency medical control centres and called for nationwide strategies., Conclusions: Members of the consensus conference acknowledged that smartphone-based activation of CFR to OHCA saves lives. The statements generated by the consensus conference may assist the public, healthcare services and governments to utilise these systems to their full potential, and direct the research community towards fields that still need to be addressed.

Drug resistance and dose-limiting toxicities are significant barriers for treatment of multiple myeloma (MM). Bone marrow microenvironment (BMME) plays a major role in drug resistance in MM. Drug delivery with targeted nanoparticles have been shown to improve specificity and efficacy and reduce toxicity. We aim to improve treatments for MM by (1) using nanoparticle delivery to enhance efficacy and reduce toxicity; (2) targeting the tumor-associated endothelium for specific delivery of the cargo to the tumor area, and (3) synchronizing the delivery of chemotherapy (bortezomib; BTZ) and BMME-disrupting agents (ROCK inhibitor) to overcome BMME-induced drug resistance. We find that targeting the BMME with P-selectin glycoprotein ligand-1 (PSGL-1)-targeted BTZ and ROCK inhibitor-loaded liposomes is more effective than free drugs, non-targeted liposomes, and single-agent controls and reduces severe BTZ-associated side effects. These results support the use of PSGL-1-targeted multi-drug and even non-targeted liposomal BTZ formulations for the enhancement of patient outcome in MM.

Background: German emergency medical services are a 2-tiered system with paramedic-staffed ambulances as the primary response, supported by prehospital emergency doctors for life-threatening conditions. As in all European health care systems, German medical practitioners are in short supply, whereas the demand for timely emergency medical care is constantly growing. In rural areas, this has led to critical delays in the provision of emergency medical care. In particular, in cases of cardiac arrest, time is of the essence because, with each passing minute, the chance of survival with good neurological outcome decreases., Objective: The project has 4 main objectives: (1) reduce the therapy-free interval through widespread reinforcement of resuscitation skills and motivating the public to provide help (ie, bystander cardiopulmonary resuscitation), (2) provide faster professional first aid in addition to rescue services through alerting trained first aiders by mobile phone, (3) make more emergency physicians available more quickly through introducing the tele-emergency physician system, and (4) enhance emergency care through improving the cooperation between statutory health insurance on-call medical services (German: Kassenärztlicher Bereitschaftsdienst) and emergency medical services., Methods: We will evaluate project implementation in a tripartite prospective and intervention study. First, in medical evaluation, we will assess the influences of various project measures on quality of care using multiple methods. Second, the economic evaluation will mainly focus on the valuation of inputs and outcomes of the different measures while considering various relevant indicators. Third, as part of the work and organizational analysis, we will assess important work- and occupational-related parameters, as well as network and regional indexes., Results: We started the project in 2017 and will complete enrollment in 2020. We finished the preanalysis phase in September 2018., Conclusions: Overall, implementation of the project will entail realigning emergency medicine in rural areas and enhancing the quality of medical emergency care in the long term. We expect the project to lead to a measurable increase in medical laypersons' individual motivation to provide resuscitation, to strengthen resuscitation skills, and to result in medical laypersons providing first aid much more frequently. Furthermore, we intend the project to decrease the therapy-free interval in cases of cardiac arrest by dispatching first aiders via mobile phones. Previous projects in urban regions have shown that the tele-emergency physician system can provide a higher availability and quality of emergency call-outs in regular health care. We expect a closer interrelation of emergency practices of statutory health insurance physicians with the rescue service to lead to better coordination of rescue and on-call services., International Registered Report Identifier (irrid): DERR1-10.2196/14358., (©Camilla Metelmann, Bibiana Metelmann, Dorothea Kohnen, Clara Prasser, Rebekka Süss, Julia Kuntosch, Dirk Scheer, Timm Laslo, Lutz Fischer, Joachim Hasebrook, Steffen Flessa, Klaus Hahnenkamp, Peter Brinkrolf. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 14.02.2020.)

Multiple myeloma (MM) remains to be incurable despite recent therapeutic advances. CD47, an immune checkpoint known as the "don't eat me" signal, is highly expressed on the surface of various cancers, allowing cancer cells to send inhibitory signals to macrophages and impede phagocytosis and immune response. In this study, we hypothesized that blocking the "don't eat me" signaling using an anti-CD47 monoclonal antibody will induce killing of MM cells. We report that CD47 expression was directly correlated with stage of the disease, from normal to MGUS to MM. Moreover, MM cells had remarkably higher CD47 expression than other cell populations in the bone marrow. These findings indicate that CD47 is specifically expressed on MM and can be used as a potential therapeutic target. Further, blocking of CD47 using an anti-CD47 antibody induced immediate activation of macrophages, which resulted in induction of phagocytosis and killing of MM cells in the 3D-tissue engineered bone marrow model, as early as 4 hours. These results suggest that macrophage checkpoint immunotherapy by blocking the CD47 "don't eat me" signal is a novel and promising strategy for the treatment of MM, providing a basis for additional studies to validate these effects in vivo and in patients., Competing Interests: Dr. Azab received research support from Vasculox Inc. to conduct this study. He also received funding from GlycoMimetic Inc.; however, this has no contribution to this study. In addition, Dr. Azab is the founder and owner of Cellatrix LLC that has an exclusive license for the 3DTEBM technology described in part of the experiments in this paper. Moreover, Dr. Azab is the founder and owner of Targeted Therapeutics LLC; however, this has no contribution to this study. Other authors state no conflicts of interest.

The establishment of more effective treatments that can circumvent chemoresistance in Multiple Myeloma (MM) is a priority. Although bortezomib (BTZ) is one of the most potent proteasome inhibitors available, still possesses limitations related to dose limiting side effects. Several strategies have been developed to improve the delivery of chemotherapies to MM by targeting different moieties expressed on MM cells to nanoparticle delivery systems (NPs), which have failed mainly due to their heterogeneous expression on these cells. Our goal was to test CD38 targeted chitosan NPs as novel targeting moiety for MM to improve the potency and efficacy of BTZ in MM cells and reduce the side effects in healthy tissue. We have showed preferential BTZ release in tumor-microenvironment, specific binding to MM cells, and an improved drug cellular uptake through BTZ diffusion from the surface and endocytosed NPs, which translated in enhanced proteasome inhibition and robust cytotoxic effect on MM cells when BTZ was administered through anti-CD38 chitosan NPs. Furthermore, the anti-CD38 chitosan NPs specifically delivered therapeutic agents to MM cells improving therapeutic efficacy and reducing side effects in vivo. The anti-CD38 chitosan NPs showed low toxicity profile allowing enhancement of proteasome-inhibitory activity and specificity of BTZ by endocytosis-mediated uptake of CD38 representing a promising therapy in MM., (Copyright © 2017 Elsevier B.V. All rights reserved.)