Understanding barriers and facilitators to palliative and end-of-life care research: a mixed method study of generalist and specialist health, social care, and research professionals.

BACKGROUND: Palliative care provision should be driven by high quality research evidence. However, there are barriers to conducting research. Most research attention focuses on potential patient barriers; staff and organisational issues that affect research involvement are underexplored. The aim of this research is to understand professional and organisational facilitators and barriers to conducting palliative care research. METHODS: A mixed methods study, using an open cross-sectional online survey, followed by working groups using nominal group techniques. Participants were professionals interested in palliative care research, working as generalist/specialist palliative care providers, or palliative care research staff across areas of North West England. Recruitment was via local health organisations, personal networks, and social media in 2022. Data were examined using descriptive statistics and content analysis. RESULTS: Participants (survey n = 293, working groups n = 20) were mainly from clinical settings (71%) with 45% nurses and 45% working more than 10 years in palliative care. 75% were not active in research but 73% indicated a desire to increase research involvement. Key barriers included lack of organisational research culture and capacity (including prioritisation and available time); research knowledge (including skills/expertise and funding opportunities); research infrastructure (including collaborative opportunities across multiple organisations and governance challenges); and patient and public perceptions of research (including vulnerabilities and burdens). Key facilitators included dedicated research staff, and active research groups, collaborations, and networking opportunities. CONCLUSIONS: Professionals working in palliative care are keen to be research active, but lack time, skills, and support to build research capabilities and collaborations. A shift in organisational culture is needed to enhance palliative care research capacity and collaborative opportunities across clinical and research settings.

An Innovation in Cancer Nursing Education Across Europe: A Pilot Evaluation.

The European Oncology Nursing Society (EONS) is a pan-European not for profit society involving approximately 28,000 cancer nurses from 32 countries in the region. The European College of Cancer Nursing (ECCN) exists under the umbrella of EONS and was established in 2020 with a strategic priority to develop, promote and deliver educational opportunities for nurses across Europe. ECCN introduced a pilot on-line education programme for 20 nurses in January 2023. This study evaluated participating nurses' views and experience of learning on the pilot programme. The study adopted a mixed method approach guided by the four levels of the Kirkpatrick theoretical framework. A dominant focus on qualitative data was used with supplementary quantitative data. The Standards for Reporting Qualitative Research (SRQR) was followed. Eleven nurses completed the pre-pilot online questionnaire (response rate 65%) and seven (n = 7) completed the post-pilot questionnaire (41% response rate). Five (n = 5) nurses participated in two focus group interviews. Data analysis resulted in the development of four overarching themes: A wider world of cancer nursing; Shapeless mentorship; Impact on Practice; Learning online and what now? On commencement of online education programmes, nurses value a structured timetable and support from nursing management to maximise engagement with the learning materials.

A multicentre evaluation and expert recommendations of use of the newly developed BioFire Joint Infection polymerase chain reaction panel.

Septic arthritis is a serious condition with significant morbidity and mortality, routinely diagnosed using culture. The FDA has recently approved the rapid molecular BioFire® Joint Infection Panel (BJIP) for synovial fluid. We aimed to evaluate the BJIP compared to culture and its potential use in patient management. A multicentre retrospective evaluation of BJIP was conducted in the UK and Ireland. Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated between the BJIP and routine culture. A multidisciplinary team (MDT) discussion addressing the optimal or potential case use of the assay practice was facilitated. Three hundred ninety-nine surplus synovial fluid samples (~ 70% from native joints) from eight centres were processed using BJIP in addition to routine culture. An increased yield of positive results was detected using BJIP compared to routine culture (98 vs 83), giving an overall PPA of 91.6% and overall NPA of 93% for the BJIP compared to culture results. The BJIP detected resistant markers and additional organisms that could influence antibiotic choices including Neisseria gonorrhoeae and Kingella kingae. The MDT agreed that the assay could be used, in addition to standard methods, in adult and children patients with specialist advice use based on local needs. Rapid results from BJIP were assessed as having potential clinical impact on patient management. Organisms not included in the panel may be clinically significant and may limit the value of this test for PJI.

Development of online cancer resources to support pre-registration nurses and allied health professionals.

Cancer rates are increasing, and more people are living with cancer and its consequences. Healthcare students will be caring for people affected by cancer in all clinical contexts. However, pre-registration programmes can include limited cancer education and not all students will have the opportunity for a clinical placement in a cancer setting. This can result in healthcare students feeling unprepared to care for people affected by cancer. To address this need, nine e-learning modules, collectively called The Foundations of Cancer Care, have been developed to support students' knowledge, understanding and confidence about cancer. This article outlines the development and peer review of The Foundations of Cancer Care. The resultant modules are freely available to all those with an Open Athens account or NHS or UK university email address via the NHS Learning Hub (https://learninghub.nhs.uk).

Bicyclic pyrimidine compounds as potent IRAK4 inhibitors.

Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a critical role in transduction of IL-1R/TLR signaling which is responsible for innate immune response. From HTS campaign, bicyclic-pyrimidine compounds have been identified as potent IRAK4 inhibitors, exhibiting good potency in both IRAK4 biochemical and LPS induced IL-23 inhibition cell-based assays. The SAR efforts were focused on further improving on-target potency, reducing PAD activities of HTS hit molecule and improving in vivo PK profiles of early lead compounds. When different aromatic rings were fused to the pyrimidine core, and with various substituents at 2- or 4-position of the pyrimidine, the impact on potency and PK properties were observed and are discussed. Selected compounds were further evaluated in IL-1ß induced IL-6 inhibition acute animal model and rodent arthritis disease model, of which compounds 33 and 39 showed good efficacy in both studies.

Emotional well-being, spiritual well-being and resilience of advanced clinical practitioners in the United Kingdom during COVID-19: an exploratory mixed method study.

AIM: To investigate the emotional and spiritual well-being and resilience of advanced clinical practitioners during COVID. BACKGROUND: Resilience is a protective factor for emotional and spiritual well-being. The pandemic has taken a toll on health professionals due to significant physical and psychological pressures. The impact of COVID-19 on well-being and resilience of advanced clinical practitioners is not known. METHOD: Three validated scales assessed resilience, emotional and spiritual well-being. Seven hundred and thirty-four responses were analysed. RESULTS: Participants have low levels of emotional and spiritual well-being. Participants with higher levels of spirituality reported greater resilience and those with higher levels of resilience reported greater well-being. CONCLUSION: Advanced clinical practitioners' emotional and spiritual well-being and resilience has been impacted significantly during the pandemic. Interventions are needed at team, service and systems levels to enhance well-being and resilience. IMPLICATIONS FOR NURSING MANAGEMENT: Worryingly low levels of well-being and resilience in advanced clinical practitioners have been found; support to increase well-being and resilience is needed. Our findings can inform policies, resources and interventions aimed at enabling positive adaptation and enhanced resilience. Understanding and responding to the scale and impact of COVID-19 on health care workers has become a key government recommendation following the pandemic.

Inhibition of IRAK4 kinase activity improves ethanol-induced liver injury in mice.

BACKGROUNDS & AIMS: Alcohol-related liver disease (ALD) is a major cause of chronic liver disease worldwide with limited therapeutic options. Interleukin-1 receptor associated kinase 4 (IRAK4), the master kinase of Toll-like receptor (TLR)/IL-1R-mediated signalling activation, is considered a novel therapeutic target in inflammatory diseases, but has not been investigated in the context of ALD. METHODS: IRAK4 phosphorylation and IRAK1 protein were analysed in liver from alcohol-related hepatitis patients and healthy controls. IRAK4 kinase activity-inactive knock-in (Irak4 KI) mice and bone marrow chimeric mice were exposed to chronic ethanol-induced liver injury. IL-1ß-induced IRAK4-mediated signalling and acute phase response were investigated in cultured hepatocytes. IRAK1/4 inhibitor was used to test the therapeutic potential for ethanol-induced liver injury in mice. RESULTS: Increased IRAK4 phosphorylation and reduced IRAK1 protein were found in livers of patients with alcoholic hepatitis. In the chronic ethanol-induced liver injury mouse model, hepatic inflammation and hepatocellular damage were attenuated in Irak4 KI mice. IRAK4 kinase activity promotes expression of acute phase proteins in response to ethanol exposure, including C-reactive protein and serum amyloid A1 (SAA1). SAA1 and IL-1ß synergistically exacerbate ethanol-induced cell death ex vivo. Pharmacological blockage of IRAK4 kinase abrogated ethanol-induced liver injury, inflammation, steatosis, as well as acute phase gene expression and protein production in mice. CONCLUSIONS: Our data elucidate the critical role of IRAK4 kinase activity in the pathogenesis of ethanol-induced liver injury in mice and provide preclinical validation for use of an IRAK1/4 inhibitor as a new potential therapeutic strategy for the treatment of ALD. LAY SUMMARY: Herein, we have identified the role of IRAK4 kinase activity in the development of alcohol-induced liver injury in mice. Hepatocyte-specific IRAK4 is associated with an acute phase response and release of proinflammatory cytokines/chemokines, which synergistically exacerbate alcohol-induced hepatocyte cell death ex vivo. Pharmacological inhibition of IRAK4 kinase activity effectively attenuates alcohol-induced liver injury in mice and could have therapeutic implications.

Donor derived HSV hepatitis in a kidney transplant recipient leading to liver fibrosis and portal hypertension.

The unexpected transmission of donor-derived infection through organ transplantation is a rare event with current donor screening practices. In this case report we describe a probable donor-derived transmission of Herpes Simplex Virus (HSV)-2 via deceased donor kidney transplantation resulting in HSV hepatitis in the recipient. This manifested as acute liver failure which resolved with appropriate anti-viral therapy. Following recovery from the acute liver insult, the patient developed fibrotic liver morphology and portal hypertension, an unusual departure from the typical course.

Effectiveness of Online Cancer Education for Nurses and Allied Health Professionals; a Systematic Review Using Kirkpatrick Evaluation Framework.

Embedding online learning within higher education can provide engaging, cost-effective, interactive and flexible education. By evaluating the impact, outcomes and pedagogical influence of online cancer and education, future curricula can be shaped and delivered by higher education providers to better meet learner, health care provider and educational commissioners' requirements for enhanced patient care and service delivery needs. Using the Kirkpatrick's four-level model of educational evaluation, a systematic review of the effectiveness of online cancer education for nurses and allied health professionals was conducted. From 101 articles, 30 papers were included in the review. Educational theory is not always employed. There is an absence of longitudinal studies to examine impact; an absence of reliability and/or validity testing of measures, limited experimental designs taking account of power and few attempts to mitigate bias. There is, however, an emerging innovative use of mobile/spaced learning techniques. Evidence for clinical and educational effectiveness is weak offering insights into experiences and participant perceptions rather than concrete quantitative data and patient-reported outcomes. More pedagogical research is merited to inform effective evaluation of online cancer education, which incorporates and demonstrates a longer-term impact.

What are the barriers to initiating end-of-life conversations with patients in the last year of life?

INTRODUCTION: Improving end of life care is a national imperative. Unsatisfactory care persists particularly in acute hospitals, with shortcomings, variability in communication and advance care planning identified as fundamental issues. This review explored the literature to identify what is known about the barriers to initiating end-of-life conversations with patients from the perspective of doctors and nurses in the acute hospital setting. METHOD: Six electronic databases were searched for potentially relevant records published between 2008 and 2015. Studies were included if the authors reported on barriers to discussing end of life with families or patients as described by doctors or nurses in hospital settings, excluding critical care. RESULTS: Of 1267 potentially relevant records, 12 were included in the review. Although there is limited high-quality evidence available, several barriers were identified. Recurrent themes within the literature related to a lack of education and training, difficulty in prognostication, cultural differences and perceived reluctance of the patient or family. CONCLUSIONS: This study illustrated that, in addressing barriers to communication, consideration needs to be extended to include how to embed good communication practice between patients and health professionals into the culture of this setting. Board level commitment is required to raise awareness of, and familiarity with, policies and protocols concerning communication and end-of-life care. Communication training should include practical skills and tools, opportunities to explore the personal beliefs of practitioners and managing their emotions, opportunities to analyse the local organisational (physical and social environment) and team barriers.

Inhibition of Janus kinase signaling during controlled mechanical ventilation prevents ventilation-induced diaphragm dysfunction.

Controlled mechanical ventilation (CMV) is associated with the development of diaphragm atrophy and contractile dysfunction, and respiratory muscle weakness is thought to contribute significantly to delayed weaning of patients. Therefore, therapeutic strategies for preventing these processes may have clinical benefit. The aim of the current study was to investigate the role of the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in CMV-mediated diaphragm wasting and weakness in rats. CMV-induced diaphragm atrophy and contractile dysfunction coincided with marked increases in STAT3 phosphorylation on both tyrosine 705 (Tyr705) and serine 727 (Ser727). STAT3 activation was accompanied by its translocation into mitochondria within diaphragm muscle and mitochondrial dysfunction. Inhibition of JAK signaling during CMV prevented phosphorylation of both target sites on STAT3, eliminated the accumulation of phosphorylated STAT3 within the mitochondria, and reversed the pathologic alterations in mitochondrial function, reduced oxidative stress in the diaphragm, and maintained normal diaphragm contractility. In addition, JAK inhibition during CMV blunted the activation of key proteolytic pathways in the diaphragm, as well as diaphragm atrophy. These findings implicate JAK/STAT3 signaling in the development of diaphragm muscle atrophy and dysfunction during CMV and suggest that the delayed extubation times associated with CMV can be prevented by inhibition of Janus kinase signaling.-Smith, I. J., Godinez, G. L., Singh, B. K., McCaughey, K. M., Alcantara, R. R., Gururaja, T., Ho, M. S., Nguyen, H. N., Friera, A. M., White, K. A., McLaughlin, J. R., Hansen, D., Romero, J. M., Baltgalvis, K. A., Claypool, M. D., Li, W., Lang, W., Yam, G. C., Gelman, M. S., Ding, R., Yung, S. L., Creger, D. P., Chen, Y., Singh, R., Smuder, A. J., Wiggs, M. P., Kwon, O.-S., Sollanek, K. J., Powers, S. K., Masuda, E. S., Taylor, V. C., Payan, D. G., Kinoshita, T., Kinsella, T. M. Inhibition of Janus kinase signaling during controlled mechanical ventilation prevents ventilation-induced diaphragm dysfunction.

Design, synthesis of diaminopyrimidine inhibitors targeting IgE- and IgG-mediated activation of Fc receptor signaling.

Using cultured human mast cells (CHMC) the optimization of 2,4-diaminopyrimidine compounds leading to 22, R406 is described. Compound 22 is a potent upstream inhibitor of mast cell degranulation and its mechanism of action is via inhibition of Syk kinase. Compound 22 has significant activity in inhibiting both IgE- and IgG-mediated activation of Fc receptor (FcR) in mast cells and basophils, and in addition inhibits Syk kinase-dependent activity of FcR-mediated activation of monocytes, macrophages, neutrophils, and B cell receptor (BCR)-mediated activation of B lymphocytes. Overall, the biological activity of 22 suggests that it has potential for application as a novel therapeutic for the treatment of an array of autoimmune maladies and hematological malignancies.

Biosciences in nurse education: is the curriculum fit for practice? Lecturers' views and recommendations from across the UK.

AIMS AND OBJECTIVES: This study aims to review the biosciences component of preregistration nursing programmes in higher education institutions across the UK through the experiences and perceptions of lecturers involved in nursing education. BACKGROUND: Studies suggest that some qualified nurses lack confidence in explaining the bio-scientific rationale for their clinical practice. Biosciences can be difficult to understand and integrate into clinical decision-making and require protected time within preregistration nurse education. In the absence of explicit national guidelines, it is unclear as to the depth and extent biosciences are taught across different institutions and the level achieved at the point of registration. DESIGN: A survey approach was adopted to generate quantitative and qualitative feedback. METHODS: Data were collected using a semi-structured questionnaire seeking the experiences and views of lecturers involved in teaching biosciences to nursing students across the UK. Data received from 10 institutions were analysed using descriptive statistics and thematic analysis. RESULTS: Lecturers reported that the hours of taught biosciences ranged from 20-113 hours, principally within the first year. This represents between 0·4-2·4% of time within a preregistration nursing programme (4600 hours). Large group lectures predominate, supplemented by smaller group or practical work, and online materials. The biosciences are assessed specifically in half the institutions surveyed and as part of integrated assessments in the rest. In relation to student feedback, all respondents stated that students consistently requested more time and greater priority for biosciences in their programme. CONCLUSIONS: This survey suggests that the number of hours spent teaching biosciences is minimal and varies widely between higher education institutions. All respondents expressed concern about the challenges of teaching difficult bio-scientific concepts to large groups in such a limited time and called for greater clarity in national guidelines to ensure that all nurses are adequately educated and assessed in bioscience subjects. RELEVANCE TO CLINICAL PRACTICE: Failure to understand the biosciences underpinning care has implications for safe and competent nursing.

Janus kinase 1/3 signaling pathways are key initiators of TH2 differentiation and lung allergic responses.

BACKGROUND: Janus kinases (JAKs) are regulators of signaling through cytokine receptors. The importance of JAK1/3 signaling on TH2 differentiation and development of lung allergic responses has not been investigated. OBJECTIVE: We sought to examine a selective JAK1/3 inhibitor (R256) on differentiation of TH subsets in vitro and on development of ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) and inflammation in an experimental model of asthma. METHODS: A selective JAK1/3 inhibitor was used to assay the importance of this pathway on induction of TH1, TH2, and TH17 differentiation in vitro. In vivo, the effects of inhibiting JAK1/3 signaling were examined by administering the inhibitor during the sensitization or allergen challenge phases in the primary challenge model or just before provocative challenge in the secondary challenge model. Airway inflammation and AHR were examined after the last airway challenge. RESULTS: In vitro, R256 inhibited differentiation of TH2 but not TH1 or TH17 cells, which was associated with downregulation of signal transducer and activator of transcription (STAT) 6 and STAT5 phosphorylation. However, once polarized, TH2 cells were unaffected by the inhibitor. In vivo, R256 administered during the OVA sensitization phase prevented the development of AHR, airway eosinophilia, mucus hypersecretion, and TH2 cytokine production without changes in TH1 and TH17 cytokine levels, indicating that selective blockade of TH2 differentiation was critical. Inhibitor administration after OVA sensitization but during the challenge phases in the primary or secondary challenge models similarly suppressed AHR, airway eosinophilia, and mucus hypersecretion without any reduction in TH2 cytokine production, suggesting the inhibitory effects were downstream of TH2 cytokine receptor signaling pathways. CONCLUSIONS: Targeting the TH2-dependent JAK/STAT activation pathway represents a novel therapeutic approach for the treatment of asthma.

Hospice nurses' views on single nurse administration of controlled drugs.

BACKGROUND: The involvement of two nurses to dispense and administer controlled drugs is routine practice in most clinical areas despite there being no legal or evidence-based rationale. Indeed, evidence suggests this practice enhances neither safety nor care. Registered nurses at two hospices agreed to change practice to single nurse dispensing and administration of controlled drugs (SNAD). Participants' views on SNAD were evaluated before and after implementation. The aim of this study was to explore the views and experiences of nurses who had implemented SNAD and to identify the views and concerns of those who had not yet experienced SNAD. METHOD: Data was obtained through semi-structured interviews. RESULTS: Qualitative thematic analysis of interview transcripts identified three key themes: practice to enhance patient benefit and care; practice to enhance nursing care and satisfaction; and practice to enhance organisational safety. CONCLUSION: The findings have implications for the understanding of influences on medicines safety in clinical practice and for hospice policy makers.

Training oncology and palliative care clinical nurse specialists in psychological skills: evaluation of a pilot study.

OBJECTIVE: National guidelines in the United Kingdom recommend training Clinical Nurse Specialists in psychological skills to improve the assessment and intervention with psychological problems experienced by people with a cancer diagnosis (National Institute for Health and Clinical Excellence, 2004). This pilot study evaluated a three-day training program combined with supervision sessions from Clinical Psychologists that focused on developing skills in psychological assessment and intervention for common problems experienced by people with cancer. METHODS: Questionnaires were developed to measure participants' levels of confidence in 15 competencies of psychological skills. Participants completed these prior to the program and on completion of the program. Summative evaluation was undertaken and results were compared. In addition, a focus group interview provided qualitative data of participants' experiences of the structure, process, and outcomes of the program. RESULTS: Following the program, participants rated their confidence in psychological assessment and skills associated with providing psychological support as having increased in all areas. This included improved knowledge of psychological theories, skills in assessment and intervention and accessing and using supervision appropriately. The largest increase was in providing psycho-education to support the coping strategies of patients and carers. Thematic analysis of interview data identified two main themes including learning experiences and program enhancements. The significance of the clinical supervision sessions as key learning opportunities, achieved through the development of a community of practice, emerged. SIGNIFICANCE OF RESULTS: Although this pilot study has limitations, the results suggest that a combined teaching and supervision program is effective in improving Clinical Nurse Specialists' confidence level in specific psychological skills. Participants' experiences highlighted suggestions for refinement and development of the program. Opportunities for further research and developments in this area are discussed.

Impact of bedside ultrasound on care in specialist palliative care units: a qualitative study.

OBJECTIVES: To explore the experiences of palliative care doctors regarding the clinical impact of ultrasound in specialist palliative care units (SPCUs). METHODS: The study adopted a qualitative research design using semistructured interviews and a reflexivity journal. Six participants were recruited through purposive and snowball sampling. Findings were analysed using framework analysis. RESULTS: Analysis used four predetermined themes: (1) practicalities, (2) clinical indications, (3) impact on patient care and service provision and (4) governance and training. Analysis identified a relationship between procedural confidence and use of ultrasound. CONCLUSIONS: Our study provides information for understanding the current use and limitations of ultrasound in SPCUs. Ultrasound leads to safer practice, especially when performing invasive procedures such as paracentesis. Development of standards around the use of, and training of staff undertaking ultrasound in specialist palliative care, are recommended.

The many cases of XFJ: suitable to drive a taxi or "killer cabbie"?

For 10 years, the refugee now known by the pseudonym XFJ attempted to gain accreditation to drive a taxi-cab. After many internal reviews and rejections by the Victorian Taxi Directorate, XFJ appealed to the Victorian Civil and Administrative Tribunal (VCAT). The difficulty for XFJ was that shortly after arriving in Australia, he had killed his estranged wife. The Supreme Court of Victoria subsequently found him not guilty of murder on the grounds of insanity. Since XFJ's mental health has been stable for many years, much of the legal argument at VCAT and the court cases that followed centred around whether he was "suitable in other respects to provide the service" of driving a taxi, as required by s 169(1)(b)(ii) of the Transport Act 1983 (Vic). This article looks at the tension between the expert medical evidence and the concept of "suitable in other respects" which XFJ's opponents claimed included the maintenance of public confidence and the meeting of community expectations.

Discovery of 5-Aryl-2,4-diaminopyrimidine Compounds as Potent and Selective IRAK4 Inhibitors.

IRAK4 kinase plays a key role in TLR/IL-1R signaling pathways that regulate innate immune responses, and if uncontrolled, it is responsible for various inflammatory disorders. By high-throughput screening (HTS) and hit-to-lead optimization, compounds with a 5-aryl-2,4-diaminopyrimidine core structure have been identified as potent IRAK4 inhibitors. A cocrystal structure of IRAK4 protein with an early lead molecule helped with understanding the structure-activity relationship and the design of the new compounds. Initial HTS hits from this series of compounds were also found to inhibit TAK1 kinase, which would cause liver toxicity and potentially bone marrow failure. Optimization of this series resulted in improved selectivity over TAK1 kinase. The TAK1 selectivity was found to be closely associated with different sizes and types of substituents at the 5-position of the pyrimidine. The impact of other pyrimidine substituents on the potency and selectivity was also explored. A few representative compounds were evaluated in IL-1ß-induced IL-6 inhibition animal model studies and showed modest efficacy.