The amino acid metabolism is essential for evading physical plasma-induced tumour cell death.

BACKGROUND: Recent studies have emphasised the important role of amino acids in cancer metabolism. Cold physical plasma is an evolving technology employed to target tumour cells by introducing reactive oxygen species (ROS). However, limited understanding is available on the role of metabolic reprogramming in tumour cells fostering or reducing plasma-induced cancer cell death. METHODS: The utilisation and impact of major metabolic substrates of fatty acid, amino acid and TCA pathways were investigated in several tumour cell lines following plasma exposure by qPCR, immunoblotting and cell death analysis. RESULTS: Metabolic substrates were utilised in Panc-1 and HeLa but not in OVCAR3 and SK-MEL-28 cells following plasma treatment. Among the key genes governing these pathways, ASCT2 and SLC3A2 were consistently upregulated in Panc-1, Miapaca2GR, HeLa and MeWo cells. siRNA-mediated knockdown of ASCT2, glutamine depletion and pharmacological inhibition with V9302 sensitised HeLa cells to the plasma-induced cell death. Exogenous supplementation of glutamine, valine or tyrosine led to improved metabolism and viability of tumour cells following plasma treatment. CONCLUSION: These data suggest the amino acid influx driving metabolic reprogramming in tumour cells exposed to physical plasma, governing the extent of cell death. This pathway could be targeted in combination with existing anti-tumour agents.

Argon Plasma Exposure Augments Costimulatory Ligands and Cytokine Release in Human Monocyte-Derived Dendritic Cells.

Cold physical plasma is a partially ionized gas expelling many reactive oxygen and nitrogen species (ROS/RNS). Several plasma devices have been licensed for medical use in dermatology, and recent experimental studies suggest their putative role in cancer treatment. In cancer therapies with an immunological dimension, successful antigen presentation and inflammation modulation is a key hallmark to elicit antitumor immunity. Dendritic cells (DCs) are critical for this task. However, the inflammatory consequences of DCs following plasma exposure are unknown. To this end, human monocyte-derived DCs (moDCs) were expanded from isolated human primary monocytes; exposed to plasma; and their metabolic activity, surface marker expression, and cytokine profiles were analyzed. As controls, hydrogen peroxide, hypochlorous acid, and peroxynitrite were used. Among all types of ROS/RNS-mediated treatments, plasma exposure exerted the most notable increase of activation markers at 24 h such as CD25, CD40, and CD83 known to be crucial for T cell costimulation. Moreover, the treatments increased interleukin (IL)-1α, IL-6, and IL-23. Altogether, this study suggests plasma treatment augmenting costimulatory ligand and cytokine expression in human moDCs, which might exert beneficial effects in the tumor microenvironment.

Cost-of-illness and Economic Evaluation of Interventions in Children and Adolescents With Chronic Pain: A Systematic Review.

OBJECTIVES: Chronic pain in children and adolescents (CPCA) is widespread with an increasing prevalence. It is associated with a decreased quality of life and an increased parental work loss. Accordingly, CPCA may pose a substantial economic burden for patients, health care payers, and society. Therefore, this systematic review aimed to synthesize (1) the results of existing cost-of-illness studies (COIs) for CPCA and (2) the evidence of economic evaluations (EEs) of interventions for CPCA. METHODS: The systematic literature search was conducted in EMBASE, MEDLINE, PsycINFO, NHS EED, and HTA Database until February 2023. Title, abstract, and full-text screening were conducted by 2 researchers. Original articles reporting costs related to CPCA published in English or German were included. Study characteristics, cost components, and costs were extracted. The quality of studies was assessed using standardized tools. All costs were adjusted to 2020 purchasing power parity US dollars (PPP-USD). RESULTS: Fifteen COIs and 10 EEs were included. The mean annual direct costs of CPCA ranged from PPP-USD 603 to PPP-USD 16,271, with outpatient services accounting for the largest share. The mean annual indirect costs ranged from PPP-USD 92 to PPP-USD 12,721. All EEs reported a decrease in overall costs in treated patients. DISCUSSION: The methodology across studies was heterogeneous limiting the comparability. However, it is concluded that CPCA is associated with high overall costs, which were reduced in all EEs. From a health-economic perspective, efforts should address the prevention and early detection of CPCA followed by specialized pain treatment.

Participatory Design of a Medication Module in an Electronic Medical Record for Paediatric Palliative Care: A Think-Aloud Approach with Nurses and Physicians.

BACKGROUND: Electronic medical records (EMRs) play a key role in improving documentation and quality of care in paediatric palliative care (PPC). Inadequate EMR design can cause incorrect prescription and administration of medications. Due to the fact of complex diseases and the resulting high level of medical complexity, patients in PPC are vulnerable to medication errors. Consequently, involving users in the development process is important. Therefore, the aim of this study was to evaluate the acceptance of a medication module from the perspective of potential users in PPC and to involve them in the development process. METHODS: A qualitative observational study was conducted with 10 nurses and four physicians using a concurrent think-aloud protocol and semi-structured qualitative interviews. A qualitative content analysis was applied based on a unified theory of acceptance and use of technology. RESULTS: Requirements from the user's perspective could be identified as possible influences on acceptance and actual use. Requirements were grouped into the categories "performance expectancies" and "effort expectancies". CONCLUSIONS: The results serve as a basis for further development. Attention should be given to the reduction of display fragmentation, as it decreases cognitive load. Further approaches to evaluation should be taken.

Planning for Implementation Success of an Electronic Cross-Facility Health Record for Pediatric Palliative Care Using the Consolidated Framework for Implementation Research (CFIR).

Pediatric palliative care (PPC) patients require years of care across professions and sectors. Sharing treatment-related information and communicating among different PPC professionals is critical to ensure good quality of care. In Germany, this communication is mostly paper-based and prone to errors. Therefore, an electronic cross-facility health record (ECHR) was participatorily designed with users, wherein information can be shared and PPC professionals can communicate with each other. As this form of electronic health record differs from existing models in Germany, there is a need for successful implementation to ensure a positive impact. Therefore, the facilitators and barriers to the implementation of ECHR in PPC were examined. Using the consolidated framework for implementation research (CFIR), transcripts of 32 interviews, 3 focus groups, and 20 think-aloud studies with PPC professionals were analyzed. CFIR indicated that the ECHR-design was viewed positively by users and can be a facilitator for implementation. Barriers exist, mainly due to the fact that the implementation is not planned, the use of the ECHR involves effort, costs are not covered, and all users must be motivated to use the ECHR for functionality. CFIR helps uncover the crux of the issues that need to be considered when planning ECHR implementation to improve care in PPC.

Evaluation of an Electronic Medical Record Module for Nursing Documentation in Paediatric Palliative Care: Involvement of Nurses with a Think-Aloud Approach.

BACKGROUND: Paediatric palliative care (PPC) is a noncurative approach to the care of children and adolescents with life-limiting and life-threatening illnesses. Electronic medical records (EMRs) play an important role in documenting such complex processes. Despite their benefits, they can introduce unintended consequences if future users are not involved in their development. AIM: The aim of this study was to evaluate the acceptance of a novel module for nursing documentation by nurses working in the context of PPC. METHODS: An observational study employing concurrent think-aloud and semi-structured qualitative interviews were conducted with 11 nurses working in PPC. Based on the main determinants of the unified theory of acceptance and use of technology (UTAUT), data were analysed using qualitative content analysis. RESULTS: The main determinants of UTAUT were found to potentially influence acceptance of the novel module. Participants perceived the module to be self-explanatory and intuitive. Some adaptations, such as the reduction of fragmentation in the display, the optimization of confusing mouseover fields, and the use of familiar nursing terminology, are reasonable ways of increasing software adoption. CONCLUSIONS: After adaptation of the modules based on the results, further evaluation with the participation of future users is required.

Participatory Design of an Electronic Cross-Facility Health Record (ECHR) System for Pediatric Palliative Care: A Think-Aloud Study.

BACKGROUND: Pediatric palliative care (PPC) patients experience years of multisectoral and professional care. An electronic cross-facility health record (ECHR) system can support the immediate exchange of information among PPC professionals. Based on a needs assessment, a prototype ECHR system was developed. METHODS: To evaluate potential users' perspective regarding the system, a qualitative observational study was conducted consisting of a concurrent think-aloud session and a semi-structured qualitative interview. RESULTS: Twenty PPC professionals (nurses, physicians) from specialized outpatient PPC teams, a PPC unit, and medical offices rated the ECHR system as a helpful tool to improve the exchange and collection of information, communication between PPC professionals, and treatment planning. From the user's point of view, the basic logic of the ECHR system should be further adapted to improve the interaction of data remirrored from patient records of outpatient and inpatient care with those entered via the system. The users wished for further functions (text search) and content (information on therapies). Some content, such as the treatment process, needs to be further adapted. CONCLUSION: The developed ECHR system needs to be more specific in some features by offering all available information; while for other features, be less specific to offer a quick overview. The ability to share information promptly and automatically was seen as a tremendous improvement to the quality of care for PPC patients.

Electronic Health Records in Specialized Pediatric Palliative Care: A Qualitative Needs Assessment among Professionals Experienced and Inexperienced in Electronic Documentation.

BACKGROUND: Currently, to the best of our knowledge, no findings exist concerning the needs of professionals in specialized pediatric palliative care (PPC) regarding electronic health records (EHRs). Several studies have highlighted benefits concerning the use of EHRs in pediatrics. However, usability is strongly affected by the degree of adaptivity to the context of application. The aim of this study is to examine the needs of professionals concerning an EHR in the specialized PPC inpatient and outpatient settings. METHODS: A qualitative research design was chosen to address the complex aspects of user demands. Focus group interviews and semi-structured one-on-one interviews were conducted with PPC professionals. N = 23 participants from inpatient and N = 11 participants from outpatient settings of specialized PPC representing various professions took part in the study. RESULTS: The findings could be grouped into four categories: (1) attitude towards the current methods of documentation, (2) attitude towards electronic documentation in general, (3) general requirements for an EHR, and (4) content requirements for an EHR. CONCLUSIONS: Professionals in specialized PPC expect and experience many benefits of using electronic documentation. Their requirements for an EHR for inpatient and outpatient settings of PPC are largely consistent with EHRs for pediatrics. However, individual specifications and adaptations are necessary for this particular setting.

Needs Assessment for the Development of an Electronic Cross-Facility Health Record (ECHR) for Pediatric Palliative Care: A Design Thinking Approach.

BACKGROUND: Pediatric palliative care (PPC) is characterized by years of multisectoral and multi-professional care. Sharing information between PPC professionals is, therefore, essential for quality care. The evidence shows that electronic cross-facility health records (ECHRs) provide useful support in this context. To our knowledge, no ECHRs have been developed through a user-centered approach for this specific setting in Germany. METHODS: Guided by design thinking, first, qualitative interviews were conducted to assess the needs of PPC professionals. Second, the elicited needs were specified in focus groups (FGs). Based on the needs stated in the interviews, prototypes of the ECHR were developed and discussed in the FGs. The indicated needs were supplemented and specified in an iterative process. The prototypes were further adapted according to these results. The unified theory of acceptance and use of technology was the basic model in the evaluation of needs. RESULTS: Across seven main categories, past and current medication, emergency view, and messaging functions were identified as the participants' desired core components of an ECHR. Utilizing design thinking facilitated the explicit articulation of user needs. CONCLUSIONS: Developing an ECHR with the content identified would allow for real-time data during emergencies, tracking what other PPC professionals have done, and making the applied treatments visible to others. This would offer a broader picture of the complex conditions common to PPC.

Participatory Design of an Electronic Medical Record for Paediatric Palliative Care: A Think-Aloud Study with Nurses and Physicians.

BACKGROUND: Electronic medical records (EMRs) offer a promising approach to mapping and documenting the complex information gathered in paediatric palliative care (PPC). However, if they are not well developed, poorly implemented EMRs have unintended consequences that may cause harm to patients. One approach to preventing such harm is the involvement of users in the participatory design to ensure user acceptance and patient safety. Therefore, the aim of this study is to evaluate the acceptance of a novel patient chart module (PCM) as part of an EMR from the perspective of potential users in PPC and to involve these professionals in the design process. METHODS: A qualitative observational study with N = 16 PPC professionals (n = 10 nurses, n = 6 physicians) was conducted, including concurrent think aloud (CTA) and semi-structured interviews. A structured content analysis based on the Unified Theory of Acceptance and Use of Technology was applied. RESULTS: The results can be summarized in terms of general observations, performance expectancy, effort expectancy and facilitating conditions, all of which are likely to have a positive influence on acceptance of the PCM from the user perspective in the context of PPC. CONCLUSIONS: The involvement of users in the development of EMRs is important for meeting the requirements in PPC. Further software adaptations are necessary to implement these requirements.

It's All About Communication: A Mixed-Methods Approach to Collaboration Between Volunteers and Staff in Pediatric Palliative Care.

BACKGROUND: Multidisciplinary teamwork is considered central to pediatric palliative care. Although different studies state that volunteers play an essential role in palliative care, little is known about the collaboration between volunteers and staff. AIM: This study aims to explore and compare the perspectives of volunteers and staff regarding collaboration in a pediatric palliative care unit. DESIGN: A mixed-methods approach was chosen to appropriately reflect the complex aspects of collaboration. SETTING/PARTICIPANTS: Both face-to-face interviews with staff who work together with volunteers and a group discussion with all volunteers were conducted. These were supplemented by 2 questionnaires designed for this study that examined participants' characteristics and their estimation of what information volunteers need before they meet a patient. RESULTS: Nine staff members and 7 volunteers participated in this study. Their ideas of collaboration could be grouped into 3 categories: (i) factual level of collaboration, (ii) relationship level of collaboration, and (iii) overall appraisal of collaboration (suggestions for improvement). CONCLUSION: Communication can be considered a key factor in successful collaboration between volunteers and staff. Because many patients in pediatric palliative care units are not able to communicate verbally, good information flow between volunteers and staff is crucial for ensuring quality patient care. Moreover, communication is the key to establishing a team philosophy by clarifying roles and building relationships between volunteers and staff.

CD96 interaction with CD155 via its first Ig-like domain is modulated by alternative splicing or mutations in distal Ig-like domains.

The adhesion receptor CD96 (TACTILE) is a transmembrane glycoprotein possessing three extracellular immunoglobulin-like domains. Among peripheral blood cells, CD96 is expressed on T cells as well as NK cells and a subpopulation of B cells. A possible function of this receptor in NK cell-mediated killing activities was suggested recently. Moreover, CD96 was described as a tumor marker for T-cell acute lymphoblastic leukemia and acute myeloid leukemia. CD96 binds to CD155 (poliovirus receptor) and nectin-1, an adhesion receptor related to CD155. Here we report that human but not mouse CD96 is expressed in two splice variants possessing either an I-like (variant 1) or V-like (variant 2) second domain. With the notable exception of an AML tumor sample, variant 2 predominates in all the CD96-expressing cell types and tissues examined. Using chimeric human/murine CD96 receptors, we show that the interaction with its ligands is mediated via the outermost V-like domain. In contrast to mouse, however, the binding of human CD96 to CD155 is sensitive to the characteristics of the two downstream domains. This is illustrated by a significantly weaker CD96/CD155 interaction mediated by variant 1 when compared with variant 2. Moreover, recent evidence suggested that mutations in human CD96 correlate with the occurrence of a rare form of trigonocephaly. One such mutation causing a single amino acid exchange in the third domain of human CD96 decreased the capacity of both variants to bind to CD155 considerably, suggesting that a CD96-driven adhesion to CD155 may be crucial in developmental processes.