Molecular Characterization of Juxtaglomerular Cell Tumors: Evidence of Alterations in MAPK-RAS Pathway.

Juxtaglomerular cell tumor (JGCT) is a rare neoplasm, part of the family of mesenchymal tumors of the kidney. Although the pathophysiological and clinical correlates of JGCT are well known, as these tumors are an important cause of early-onset arterial hypertension refractory to medical treatment, their molecular background is unknown, with only few small studies investigating their karyotype. Herein we describe a multi-institutional cohort of JGCTs diagnosed by experienced genitourinary pathologists, evaluating clinical presentation and outcome, morphologic diversity, and, importantly, the molecular features. Ten JGCTs were collected from 9 institutions, studied by immunohistochemistry, and submitted to whole exome sequencing. Our findings highlight the morphologic heterogeneity of JGCT, which can mimic several kidney tumor entities. Three cases showed concerning histologic features, but the patient course was unremarkable, which suggests that morphologic evaluation alone cannot reliably predict the clinical behavior. Gain-of-function variants in RAS GTPases were detected in JGCTs, with no evidence of additional recurrent genomic alterations. In conclusion, we present the largest series of JGCT characterized by whole exome sequencing, highlighting the putative role of the MAPK-RAS pathway.

Integrating compression therapy into heart failure and lymphoedema management.

Heart failure (HF) and lymphoedema often co-exist, significantly affecting the quality of life and requiring complex management. Heart Failure, characterised by reduced cardiac function, affects around 1 million people in the UK. Lymphoedema, involving lymphatic failure, affects 4 to 29 per 1000 individuals, particularly older adults. Traditionally heart failure management focuses on medication, while lymphoedema relies on compression therapy (CT). The article examines the integration of CT to treat lymphoedema with coexisting HF. Evidence suggests that with careful management and multidisciplinary collaboration, CT can be safely used in stable HF patients to manage lymphoedema, improving overall treatment outcomes and patient wellbeing. This approach requires adherence to guidelines and a holistic, patient-centred care model. Debates about CT for lymphoedema in the presence of HF highlight the need for patient-focused and all-encompassing care. Practitioners must consider the broader context of both conditions and collaborate with colleagues and patients to make informed treatment decisions.

APPLICATION OF A NOVEL ASPERGILLUS LATERAL-FLOW DEVICE IN THE DIAGNOSIS OF ASPERGILLOSIS IN CAPTIVE GENTOO PENGUINS (PYGOSCELIS PAPUA PAPUA).

Aspergillosis is the primary fungal disease affecting captive penguins globally. Its diagnosis remains challenging, and currently no tests are both sensitive and specific for the detection of early infection. The present study evaluated a recently developed Aspergillus lateral-flow device (AspLFD) for the detection of Aspergillus spp. antigen in plasma and glottis mucus from captive penguins. In a pilot retrospective study, banked frozen plasma samples from captive penguins were reviewed: samples from 11 gentoo penguins (Pygoscelis papua papua) and 4 king penguins (Aptenodytes patagonicus) fulfilled the inclusion criteria and were used in the analysis. Positive plasma AspLFD test results were found in 80% (four of five) of the aspergillosis-positive cases tested. All of the aspergillosis-negative cases tested negative (10 of 10) on the AspLFD test. In a cohort prospective study, paired plasma and glottis swab samples were opportunistically and nonrandomly collected from captive gentoo penguins. In total, 26 penguins were tested. In the negative control group, AspLFD test was negative on plasma and swab in 100% of birds (14 of 14). In the aspergillosis-positive group, AspLFD test was positive on plasma samples from 33% (4 of 12) of birds, on swab samples from 50% (6 of 12) of birds, and on either plasma or swab samples from 75% (9 of 12) of birds. The AspLFD is currently used for the diagnosis of aspergillosis in humans and also shows promise for use in penguins. Larger prospective studies are recommended.

DOCKopathies: A systematic review of the clinical pathologies associated with human DOCK pathogenic variants.

The Dedicator of Cytokinesis (DOCK) family (DOCK1-11) of genes are essential mediators of cellular migration, growth, and fusion in a variety of cell types and tissues. Recent advances in whole-genome sequencing of patients with undiagnosed genetic disorders have identified several rare pathogenic variants in DOCK genes. We conducted a systematic review and performed a patient database and literature search of reported DOCK pathogenic variants that have been identified in association with clinical pathologies such as global developmental delay, immune cell dysfunction, muscle hypotonia, and muscle ataxia among other categories. We then categorized these pathogenic DOCK variants and their associated clinical phenotypes under several unique categories: developmental, cardiovascular, metabolic, cognitive, or neuromuscular. Our systematic review of DOCK variants aims to identify and analyze potential DOCK-regulated networks associated with neuromuscular diseases and other disease pathologies, which may identify novel therapeutic strategies and targets. This systematic analysis and categorization of human-associated pathologies with DOCK pathogenic variants is the first report to the best of our knowledge for a unique class in this understudied gene family that has important implications in furthering personalized genomic medicine, clinical diagnoses, and improve targeted therapeutic outcomes across many clinical pathologies.

International, multi-disciplinary, cross-section study of pain knowledge and attitudes in nursing, midwifery and allied health professions students.

BACKGROUND: Persistent pain is a highly prevalent, global cause of disability. Research suggests that many healthcare professionals are not well equipped to manage pain, and this may be attributable at least in part to undergraduate education. The primary aim of this study was to quantify and compare first and final year nursing, midwifery and allied health professional (NMAHP) students' pain related knowledge and attitudes. The secondary aim was to explore what factors influence students' pain related knowledge and attitudes. METHODS: In this cross-sectional study, 1154 first and final year healthcare students, from 12 universities in five different countries completed the Revised Neurophysiology of Pain Quiz (RNPQ) [knowledge] and the Health Care Providers Pain and Impairment Relationship Scale (HC-PAIRS) [attitudes]. RESULTS: Physiotherapy was the only student group with statistically and clinically improved pain related knowledge [mean difference, 95% CI] (3.4, 3.0 to 3.9, p = 0.01) and attitudes (-17.2, -19.2 to 15.2, p = 0.01) between first and final year. Pain education teaching varied considerably from course to course (0 to 40 h), with greater levels of pain related knowledge and attitudes associated with higher volumes of pain specific teaching. CONCLUSIONS: There was little difference in pain knowledge and attitudes between all first and final year NMAHP students other than physiotherapy. This suggests that for most NMAHP disciplines, undergraduate teaching has little or no impact on students' understanding of pain. There is an urgent need to enhance pain education provision at the undergraduate level in NMAHPs. TRIAL REGISTRATION: The study protocol was prospectively registered at ClinicalTrials.Gov NCT03522857 .

'Owning the space'-person-centred practice in a 100% single-room acute-care environment: an ethnographic study.

AIMS AND OBJECTIVES: Exploring the influence of the 100% single-room environment on staff and patient experience of person-centred practice in an acute-care setting. BACKGROUND: Current building guidance for the NHS advocates increasing the single-room inpatient environment. There is little evidence of the impact of this design in adult acute-care settings on the experience and delivery of person-centred care. DESIGN: Ethnography, underpinned by McCormack and McCance's Person-centred Practice Framework. METHODS: Data collection took place between March and June 2018. Staff and patients in a National Health Service hospital in the United Kingdom took part in observations of practice (n = 108 hours); face to face inpatient interviews (n = 9); and participatory reflective staff groups (n = 3). A reflexive journal was kept by the researcher throughout the study. Reporting adhered to the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. RESULTS: Themes relating to care delivery and interactions were identified. Staff and patients' views converged around visibility and isolation. Patients appreciated the privacy afforded by the single rooms, while staff experienced a psychological shift, being viewed (and viewing themselves) as 'visitors'. There was space for more sympathetic presencing, encouraging patients to speak more openly, to facilitate knowing and authentic engagement. However, time remained an issue resulting in more task-focused care. CONCLUSION: Changes to the physical environment have an impact on the delivery and experience of person-centred practice. While the facilities enhance patient experience, the interweaving of engagement, emotional support and the development of therapeutic relationships remain challenging.

Exploring how key performance indicators influence nursing and midwifery practice: A mixed-methods study.

AIMS: To scope the key performance indicators (KPIs) used in nursing and midwifery across the United Kingdom and Republic of Ireland and explore how they influence practice in healthcare organizations. DESIGN: The study adopted a sequential, exploratory mixed-methods design. METHODS: Phase 1 incorporated a multiple-choice questionnaire completed by 77 Directors of Nursing recruited using voluntary response sampling. In phase 2, 35 nurses and midwives who were working at executive, senior manager and clinical levels, participated in semi-structured interviews. Data collection of both phases was conducted from January 2016 to October 2016. FINDINGS: Quantitative data revealed over 100 nursing and midwifery-specific KPIs. National requirements were a deciding factor in KPI selection, while clinical involvement was mainly through data collection. Respondents stated that they used patient experience KPIs, but only one was assessed as valid. Thematic analysis identified two themes: The leadership challenge (including 'voiceless in the national conversation', 'aligning KPIs in the practice context' and 'listening to those who matter'); and taking action (including 'establishing ownership and engaging staff', 'checks and balances' and 'closing the loop'). CONCLUSION: The large volume of KPI measurement taking place makes meaningful evaluation of performance and quality of care difficult, both in and across organizations. Nurses and midwives require enhanced knowledge of the nature and purpose of KPIs, as evidence gained from KPI data collection is insufficient to lead to improvements in practice. A practice context that encourages collective leadership, where multiple sources of evidence are gathered and everyone is included in KPI evaluation and subsequent decision-making, is key. IMPACT: This study adds to the body of evidence on KPI understanding. It informs the future effective management of indicators that will facilitate the delivery of meaningful care and reduce the cost, time and effort invested in the implementation of KPIs and data management.

Implementing and measuring person-centredness using an APP for knowledge transfer: the iMPAKT app.

OBJECTIVE: The aim of the study was to evaluate a technological solution in the form of an App to implement and measure person-centredness in nursing. The focus was to enhance the knowledge transfer of a set of person-centred key performance indicators and the corresponding measurement framework used to inform improvements in the experience of care. DESIGN: The study used an evaluation approach derived from the work of the Medical Research Council to assess the feasibility of the App and establish the degree to which the App was meeting the aims set out in the development phase. Evaluation data were collected using focus groups (n = 7) and semi-structured interviews (n = 7) to capture the impact of processes experienced by participating sites. SETTING: The study was conducted in the UK and Australia in two organizations, across 11 participating sites. PARTICIPANTS: 22 nurses from 11 sites in two large health care organizations were recruited on a voluntary basis. INTERVENTION: Implementing the KPIs and measurement framework via the APP through two cycles of data collection. MAIN OUTCOME MEASURES: The main outcome was to establish feasibility in the use of the App. RESULTS: The majority of nurse/midwife participants found the App easy to use. There was broad consensus that the App was an effective method to measure the patient experience and generated clear, concise reports in real time. CONCLUSIONS: The implementation of the person-centred key performance indicators using the App enhanced the generation of meaningful data to evidence patient experience across a range of different clinical settings.

Implementing person-centred key performance indicators to strengthen leadership in community nursing: A feasibility study.

AIMS: To explore the utility and feasibility of implementing eight person-centred nursing key performance indicators in supporting community nurses to lead the development of person-centred practice. BACKGROUND: Policy advocates person-centred health care, but few quality indicators exist that explicitly focus on evaluating person-centred practice in community nursing. Current quality measurement frameworks in the community focus on incidences of poor or missed opportunities for care, with few mechanisms to measure how clients perceive the care they receive. METHODS: An evaluation approach derived from work of the Medical Research Council was used, and the study was underpinned by the Person-centred Practice Framework. Participatory methods were used, consistent with person-centred research. RESULTS: Data were thematically analysed, revealing five themes: giving voice to experience; talking the language of person-centredness; leading for cultural change; proud to be a nurse; and facilitating engagement. CONCLUSIONS: The findings suggest that implementing the eight person-centred nursing key performance indicators (KPIs) and the measurement framework is feasible and offers a means of evidencing person-centredness in community nursing. IMPLICATIONS FOR NURSING MANAGEMENT: Person-centred KPI data, used alongside existing quality indicators, will enable nurse managers to evidence a high standard of care delivery and assist in the development of person-centred practice.

USE OF CLINDAMYCIN IN PALLAS' CATS [OTOCOLOBUS (FELIS) MANUL] TO REDUCE JUVENILE TOXOPLASMOSIS-ASSOCIATED MORTALITY RATES.

Pallas' cat [Otocolobus (Felis) manul] experiences a high mortality rate from toxoplasmosis. During the period 2006-2016, the overall mortality rate for this species from all causes during the first year of life was 71.59% in European Association of Zoos and Aquaria institutions, with the most significant infectious cause from systemic toxoplasmosis (20.6%) as confirmed by postmortem examination and histopathology. Clindamycin was used starting in 2014 in two collections that had previously experienced 100% mortality rates by toxoplasmosis in kittens less than one year of age, covering key Toxoplasma gondii exposure periods for kittens (n = 17) as a prophylactic measure. This protocol resulted in a 67.03% (95% confidence interval 41.76-78.61%) reduction in the first year mortality rate over a two-year period to 5.88% in those animals treated.

VarSight: prioritizing clinically reported variants with binary classification algorithms.

BACKGROUND: When applying genomic medicine to a rare disease patient, the primary goal is to identify one or more genomic variants that may explain the patient's phenotypes. Typically, this is done through annotation, filtering, and then prioritization of variants for manual curation. However, prioritization of variants in rare disease patients remains a challenging task due to the high degree of variability in phenotype presentation and molecular source of disease. Thus, methods that can identify and/or prioritize variants to be clinically reported in the presence of such variability are of critical importance. METHODS: We tested the application of classification algorithms that ingest variant annotations along with phenotype information for predicting whether a variant will ultimately be clinically reported and returned to a patient. To test the classifiers, we performed a retrospective study on variants that were clinically reported to 237 patients in the Undiagnosed Diseases Network. RESULTS: We treated the classifiers as variant prioritization systems and compared them to four variant prioritization algorithms and two single-measure controls. We showed that the trained classifiers outperformed all other tested methods with the best classifiers ranking 72% of all reported variants and 94% of reported pathogenic variants in the top 20. CONCLUSIONS: We demonstrated how freely available binary classification algorithms can be used to prioritize variants even in the presence of real-world variability. Furthermore, these classifiers outperformed all other tested methods, suggesting that they may be well suited for working with real rare disease patient datasets.

Laparoscopic repair of an umbilical hernia in a Western chimpanzee (Pan troglodytes verus) rescued in Sierra Leone.

Laparoscopic umbilical hernia repair was performed in an adult female Western chimpanzee (Pan troglodytes verus) in a rescue centre in Sierra Leone. Biological mesh and laparoscopic spiral tacks via three 5 mm laparoscopy ports were used to close a 4 cm hernia. The chimpanzee recovered quickly and the hernia did not recur.

The experience of person-centred practice in a 100% single-room environment in acute care settings-A narrative literature review.

AIMS AND OBJECTIVES: To review published research into the staff and adult patient experience of person-centred practice in a 100% single-room environment in acute care. BACKGROUND: There has been a significant move towards the 100% single-room environment within healthcare systems. Furthermore, there has been a global move for developing person-centred practice in a range of healthcare settings. Some studies have linked the role of the physical environment to patient outcomes and improved patient satisfaction; however, these are limited. Overall, there is little evidence in the international literature of the experience of care in single rooms in adult, acute care settings. DESIGN: A narrative description was developed using the major constructs of the person-centred practice framework (PcPF). The PRISMA checklist provided additional rigour. METHOD: Problems, Exposure, Outcomes (PEO) refined the search terms to: person-centred, adult acute care, single room, staff experience and patient experience. CINAHL, Medline Ovid, Psycinfo, Embase, Web of Science and Scopus were searched for full-text English language papers of empirical studies published between 2012-2017. PRISMA illustrated final paper determination, and the CASP/EPHPP frameworks were used for a critical appraisal of the 12 selected papers. RESULTS: The literature recognises the increasing complexity of health care in the acute care environment globally. The international literature available identifies staffs' desire to practise person-centredness, but much of the evidence is focused on care delivery. The impact of the single-room environment on person-centred practice links mainly to the constructs of the care environment and person-centred processes within the PcPF. CONCLUSION: This review focuses on empirical studies relating to person-centred practice in the single-room environment published in the last 5 years. While there is a significant body of work relating to person-centredness and the delivery of person-centred practice, and the impact of the environment on care delivery, there appears to limited evidence linking person-centred practice, staff and patient experience and the single-room environment. RELEVANCE TO CLINICAL PRACTICE: By understanding the context in which care is delivered, multiprofessional teams can explore how the delivery of person-centred practice may be influenced by the physical environment and what changes to culture, systems and processes may be required to enhance the experience of care for patients and the delivery of care for staff.

The development of the Person-Centred Situational Leadership Framework: Revealing the being of person-centredness in nursing homes.

AIMS AND OBJECTIVES: To implement and evaluate the effect of using the Person-Centred Situational Leadership Framework to develop person-centred care within nursing homes. BACKGROUND: Many models of nursing leadership have been developed internationally in recent years but do not fit with the emergent complex philosophy of nursing home care. This study develops the Person-Centred Situational Leadership Framework that supports this philosophy. It forms the theoretical basis of the action research study described in this article. METHODS: This was a complex action research study using the following multiple methods: nonparticipatory observation using the Workplace Culture Critical Analysis Tool (n = 30); critical and reflective dialogues with participants (n = 39) at time 1 (beginning of study), time 2 (end of study) and time 3 (6 months after study had ended); narratives from residents at time 1 and time 2 (n = 8); focus groups with staff at time 2 (n = 12) and reflective field notes. Different approaches to analyse the data were adopted for the different data sources, and the overall results of the thematic analysis were brought together using cognitive mapping. RESULTS: The Person-Centred Situational Leadership Framework captures seven core attributes of the leader that facilitate person-centredness in others: relating to the essence of being; harmonising actions with the vision; balancing concern for compliance with concern for person-centredness; connecting with the other person in the instant; intentionally enthusing the other person to act; listening to the other person with the heart; and unifying through collaboration, appreciation and trust. CONCLUSIONS: This study led to a theoretical contribution in relation to the Person-Centred Practice Framework. It makes an important key contribution internationally to the gap in knowledge about leadership in residential care facilities for older people. RELEVANCE TO CLINICAL PRACTICE: The findings can be seen to have significant applicability internationally, across other care settings and contexts.

Exploring psychological safety as a component of facilitation within the Promoting Action on Research Implementation in Health Services framework.

AIMS AND OBJECTIVES: To explore holistic facilitation as an approach to enable the healthcare team to critically analyse practice and enhance patient care. BACKGROUND: Globally, the challenge of changing healthcare practices for enhanced patient care is the focus of much attention. Facilitation is emerging as an important approach to assist healthcare teams to explore and improve their practice. Within the Promoting Action on Research Implementation in Health Services framework, which has been tested in an international arena, facilitation is a key element of operationalising collaborative changes in practice. This study uses the framework to explore holistic facilitation and the concept of psychological safety. DESIGN: An Emancipatory Action Research approach was used. METHODS: Facilitated critical reflection was undertaken with the healthcare team working in an abdominal surgical unit. In addition, the lead researcher maintained a reflexive journal. Data were analysed using thematic analysis. Eighty-five per cent (n = 48) of nursing staff and individual participants from other parts of the healthcare team (n = 3) participated in the two-year study. RESULTS: Data revealed 14 sub-themes that impacted upon the culture of the unit. These were as follows: support, leadership, oppressed behaviours, communication, interruptions, power imbalance, horizontal violence, threat, autonomy, distorted perceptions, vulnerability, value, trust and time. Psychological safety, leadership and oppressed behaviours emerged as three key themes in the practice context. CONCLUSIONS: There is a need to create psychologically safe spaces in environments where insufficient support, weak leadership and oppressed behaviours are apparent. Psychological safety enables individuals to feel safe to engage in difficult conversations and consider changes to practice. In a theoretical contribution to the area of facilitation, it is proposed that the additional element of psychological safety needs to be incorporated into facilitation models, in particular, the Promoting Action on Research Implementation in Health Services framework, to more accurately reflect the complexities of working with healthcare teams. RELEVANCE TO PRACTICE: The pressure on healthcare environments continues to increase. To achieve the necessary skills to lead and develop services requires more than simply highlighting what is wrong with practice. Creating psychologically safe spaces, using holistic facilitation, is essential to enabling healthcare teams to critically analyse practice and enhance patient care.

Evaluating a nurse mentor preparation programme.

Following the introduction of a regional nurse mentor preparation programme, research was undertaken within a health and social care trust to explore both the trainee mentors' and their supervisors' perception of this new programme. A qualitative study involving focus groups was undertaken. The focus groups comprised a total of twelve participants including five trainee mentors and seven supervisors (experienced mentors) who had recently completed a mentor preparation programme. Data were analysed using Braun and Clarke's thematic analysis. Three themes were identified from the data: personal investment (including the emotional impact of mentoring) contextual perceptions (environmental factors such as time) and intellectual facets (related to personal and professional growth). Comprehensive preparation for mentors appears to be effective in developing mentors with the ability to support nursing students in practice. However, further study is required to explore how to support mentors to balance the demands of the mentoring role with the delivery of patient care.

Acceptability of a Mobile App (iMPAKT) for Measurement and Implementation of Person-Centredness: Mixed-Methods Study.

This study tested the acceptability of the iMPAKT App with end users. Cognitive task analysis and semi-structured interviews were used. Twelve participants took part. The majority of tasks were found to be easy to complete but issues were identified with a section of the app that provides Speech-To-Text transcription of patients speaking about their experience of care. Artificial Intelligence (AI) based systems may be needed to address these limitations. Overall views on acceptability of the app were positive and participants valued how it could be used to support practice improvement initiatives and large scale collection of person-centred measures.

Pharmacogenomics for Prader-Willi syndrome: caregiver interest and planned utilization.

Aim: The study aim was to determine caregiver interest and planned utilization of pharmacogenomic (PGx) results for their child with Prader-Willi syndrome. Methods: Caregivers consented to PGx testing for their child and completed a survey before receiving results. Results: Of all caregivers (n = 48), 93.8% were highly interested in their child's upcoming PGx results. Most (97.9%) planned to share results with their child's medical providers. However, only 47.9% of caregivers were confident providers would utilize the PGx results. Conclusion: Caregivers are interested in utilizing PGx but are uncertain providers will use these results in their child's care. More information about provider comfort with PGx utilization is needed to understand how PGx education would benefit providers and ultimately patients with PGx results.

Vitamin D status and variable responses to supplements depend in part on genetic factors in adults with cystic fibrosis.

Vitamin D sufficiency has been difficult to achieve consistently in patients with cystic fibrosis (CF), even with robust oral supplements. To assess vitamin D status and resistance to supplementation, we studied 80 adults using 25-hydroxyvitamin D (25OHD) determinations and whole genome sequencing to construct polygenic risk scores (PRS) that aggregate variants associated with vitamin D status. The results revealed that 30 % of patients were below the threshold of 30 ng/mL and thus should be regarded as insufficient despite normal vitamin E status, a reflection of adherence to fat soluble vitamin supplementation. The PRS values were significantly correlated with 25OHD concentrations, confirming our results in children with CF, and indicating that genetic factors play a role and have implications for therapy.

Consumers' perceptions of transitions from assertive community treatment to less intensive services.

When first conceptualized, it was thought that individuals with severe mental illness who needed assertive community treatment (ACT) would need ACT for life. Today, ACT-for-life is contrary to recovery-based principles, and teams routinely transition consumers to less intensive services. However, there is little qualitative information about the experiences of consumers who transition from ACT. To address this gap in our knowledge, we conducted semi-structured interviews with 11 consumers who had transitioned from ACT to case management services. Consumers expressed feelings of loss and frustration about transitioning from ACT to case management services. Findings underscore the importance of facilitating open dialogue about transitions with consumers, managing consumers' expectations of post-transition services, and facilitating consumer independence prior to transition. ACT teams should be deliberate about preparing consumers for transitions from ACT. More research is needed about facilitating successful transitions from ACT.