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.

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.

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).

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.

Optimization of Pyrimidine Compounds as Potent JAK1 Inhibitors and the Discovery of R507 as a Clinical Candidate.

Janus kinases (JAK) play a critical role in JAK/signal transducer and activator of transcription (STAT) signaling pathways that mediate immune response and cell growth. From high-throughput screening (HTS) hit to lead optimization, a series of pyrimidine compounds has been discovered as potent JAK1 inhibitors with selectivity over JAK2. Cell-based assays were used as primary screening methods for evaluating potency and selectivity, the results were further assessed and confirmed by biochemical and additional cellular assays for lead molecules. Also discussed is the unique correlation between a trifluomethyl group and CYP3A4 inhibition in the presence of NADPH, the activity of which was successfully decreased with the reduction of fluoro-atoms, increasing IC50 from 0.5 µM to >10 µM. The development of novel and scalable synthetic routes for amino-phenyl intermediates was essential for the discovery of late-stage lead molecules, including clinical candidate R507 (33). In preclinical studies, 33 exhibited great efficacy in mouse studies by inhibiting IFNγ expression induced by IL-2 and in a rat collagen-induced arthritis disease model.

Characterization of Selective and Potent JAK1 Inhibitors Intended for the Inhaled Treatment of Asthma.

Purpose: Janus kinase 1 (JAK1) is implicated in multiple inflammatory pathways that are critical for the pathogenesis of asthma, including the interleukin (IL)-4, IL-5, IL-13, and thymic stromal lymphopoietin cytokine signaling pathways, which have previously been targeted to treat allergic asthma. Here, we describe the development of AZD0449 and AZD4604, two novel and highly selective JAK1 inhibitors with promising properties for inhalation. Methods: The effects of AZD0449 and AZD4604 in JAK1 signaling pathways were assessed by measuring phosphorylation of signal transducer and activator of transcription (STAT) proteins and chemokine release using immunoassays of whole blood from healthy human volunteers and rats. Pharmacokinetic studies performed on rats evaluated AZD0449 at a lung deposited dose of 52 µg/kg and AZD4604 at 30 µg/kg. The efficacy of AZD0449 and AZD4604 was assessed by evaluating lung inflammation (cell count and cytokine levels) and the late asthmatic response (average enhanced pause [Penh]). Results: Both compounds inhibited JAK1-dependent cytokine signaling pathways in a dose-dependent manner in human and rat leukocytes. After intratracheal administration in rats, both compounds exhibited low systemic exposures and medium-to-long terminal lung half-lives (AZD0449, 34 hours; AZD4604, 5 hours). Both compounds inhibited STAT3 and STAT5 phosphorylation in lung tissue from ovalbumin (OVA)-challenged rats. AZD0449 and AZD4604 also inhibited eosinophilia in the lung and reduced the late asthmatic response, measured as Penh in the OVA rat model. Conclusion: AZD0449 and AZD4604 show potential as inhibitors of signaling pathways involved in asthmatic immune responses, with target engagement demonstrated locally in the lung. These findings support the clinical development of AZD0449 and AZD4604 for the treatment of patients with asthma.

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.

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.

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.

Nasal fentanyl and buccal midazolam carer administration 'as needed' for breakthrough symptom control in a specialist palliative care unit: a nested qualitative study.

INTRODUCTION: When people are dying and unable to take oral medication, injectable medication is commonly used, usually administered by healthcare professionals. There may be delays to symptom relief due to travel to the person's home. In a randomised controlled trial (RCT) previously reported, nasal fentanyl (NF) or buccal midazolam (BM) were administered by lay carers in a hospice. OBJECTIVE: (1) To report experiences of lay carers who administered NF and BM for symptom control and (2) To use feedback to develop guidance informing a future definitive RCT to determine whether NF and BM administered by lay carers can lead to timely, improved symptom control for people dying at home and fewer 'emergency' community nursing visits than standard breakthrough medication administered by healthcare professionals. MATERIAL AND METHODS: Semistructured interviews with lay carers who gave trial medication were conducted. Interview data were analysed using a stage by stage method to code and categorise transcripts. FINDINGS: The six themes were: (1) Participation-lay carers welcomed the opportunity to administer medication; (2) Ease of use-lay carers found preparations easy to use; (3) How things could have been done differently-lay carers would have liked access to trial drugs at home; (4) Training-lay carers were happy with the training they received; (5) Timing-lay carers liked the immediacy of trial drugs and (6) Evaluation-assessing symptom intensity and drug efficacy. CONCLUSIONS: Participation was acceptable to patients and lay carers, and beneficial for symptom relief. The findings will inform planning for a future community-based study.

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.

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.

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.

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.

The Selective JAK1/3-Inhibitor R507 Mitigates Obliterative Airway Disease Both With Systemic Administration and Aerosol Inhalation.

BACKGROUND: The efficacy of selective Janus kinase 1/3 inhibitor R507 to prevent obliterative airway disease was analyzed in preclinical airway transplantation models. METHODS: Orthotopic trachea transplantations were performed between Lewis donors and Brown Norway rat recipients. Oral everolimus (4 mg/kg once per day) or oral respective inhaled R507 (60 mg/kg twice per day, each) was used for immunosuppression. Grafts were retrieved after 6 or 60 days. Toxicity and anti-inflammatory effects of R507 were analyzed on human airway epithelial cells. RESULTS: In 6-day animals, oral and inhaled R507 more potently diminished mononuclear graft infiltration than everolimus and preserved ciliated pseudostratified columnar respiratory epithelium. Everolimus and R507 similarly suppressed systemic cellular and humoral immune activation. In untreated rats, marked obliterative airway disease developed over 60 days. Oral and inhaled R507 was significantly more effective in reducing airway obliteration and preserved the morphology of the airway epithelium. Luciferase-positive donors revealed that a substantial amount of smooth muscle cells within the obliterative tissue was of donor origin. Only everolimus but not R507, adversely altered kidney function and lipid profiles. The R507 aerosol did not show airway toxicity in vitro but effectively suppressed activation of inflammatory signaling pathways induced by IL-1ß. CONCLUSIONS: The Janus kinase 1/3 inhibitor R507 is a very well-tolerated immunosuppressant that similarly diminished obliterative airway disease with systemic or inhaled administration.

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.

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.

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.