POU2F3-expressing intraepithelial small-cell carcinoma with mixed small-cell carcinoma and conventional-type urothelial carcinoma of the urinary bladder.

Based on lineage-specific transcription factors, small-cell neuroendocrine carcinoma (SmCC) of the urinary bladder has recently been subtyped into three molecular subtypes: ASCL1, NEUROD1 and POU2F3. The latter is a master transcriptional regulator of tuft cells (TCs) which are rare solitary cells found in various mucosal epithelia such as the gastrointestinal tract, but which have not been reported in the bladder. The POU2F3 subtype shows low or absent neuroendocrine marker expression. A case of mixed SmCC and conventional-type urothelial carcinoma (CUC) of the urinary bladder with POU2F3-expressing intraepithelial small-cell carcinoma in keeping with a tuft cell phenotype, arising in association with intestinal metaplasia (IM) is described. The presence of POU2F3-expressing cells in normal urothelium, cystitis cystica glandularis and IM of the urinary bladder is demonstrated in separate cases of cystitis cystica glandularis with IM. Also, POU2F3 expression is identified in a subset of bladder SmCC.

Use of perioperative telotristat in a patient with carcinoid heart disease.

Summary: Carcinoid heart disease is a rare complication of carcinoid syndrome, resulting in right-sided valvular heart disease and subsequent heart failure due to long-term exposure to vasoactive substances. The management of this condition is complex, often requiring surgical intervention. Current perioperative regimens entail the use of prophylactic somatostatin analogs to prevent carcinoid crisis; however, regimens vary widely among practitioners and evidence supporting their efficacy in this clinical setting is mixed. This case report describes the perioperative management of a 65-year-old man with carcinoid heart disease requiring tricuspid and pulmonary valve replacement surgery. As an adjunct to somatostatin analog therapy, the novel tyrosine hydroxylase inhibitor, telotristat, was initiated preoperatively. This combination resulted in normalization of preoperative urinary 5-HIAA levels. The patient successfully underwent tricuspid and pulmonic valve replacement without evidence of carcinoid crisis. This clinical case is the first published documenting the use of telotristat in the perioperative period in a patient with carcinoid syndrome and carcinoid heart disease and was associated with a good long-term outcome despite the high-risk nature of the case. Learning points: Carcinoid crisis is a life-threatening complication of carcinoid syndrome, resulting in hemodynamic instability, bronchospasm, and arrhythmia. Cardiac surgical patients with carcinoid syndrome present a unique challenge as they are subject to physiologic conditions and medications which can potentiate intraoperative carcinoid crisis. Perioperative management of patients with carcinoid syndrome currently entails the use of prophylactic somatostatin analogs; however, these agents do not prevent carcinoid crisis in all cases. Telotristat, a tryptophan hydroxylase inhibitor, shows promise as an adjunctive therapy to somatostatin analogs to reduce the risk of intraoperative carcinoid crisis.

The context, contribution and consequences of addressing the COVID-19 pandemic: A qualitative exploration of executive nurses' perspectives.

AIMS: To explore (1) the context in which nursing executives were working, (2) nursing's contribution to the healthcare response and (3) the impact from delivering healthcare in response to the pandemic. DESIGN: Retrospective, constructivist qualitative study. METHODS: Individual interviews using a semi-structured interview guide were conducted between 12 February and 29 March 2021. Participants were purposively sampled from the Victorian Metropolitan Executive Directors of Nursing and Midwifery Group, based in Melbourne, Victoria the epi-centre of COVID-19 in Australia during 2020. All members were invited; 14/16 executive-level nurse leaders were participated. Individual interviews were recorded with participant consent, transcribed and analysed using thematic analysis. RESULTS: Four inter-related themes (with sub-themes) were identified: (1) rapid, relentless action required (preparation insufficient, extensive information and communication flow, expanded working relationships, constant change, organizational barriers removed); (2) multi-faceted contribution (leadership activities, flexible work approach, knowledge development and dissemination, new models of care, workforce numbers); (3) unintended consequences (negative experiences, mix of emotions, difficult conditions, negative outcomes for executives and workforce) and (4) silver linings (expanded ways of working, new opportunities, strengthened clinical practice, deepened working relationships). CONCLUSION: Responding to the COIVD-19 health crisis required substantial effort, but historical and industrial limits on nursing practice were removed. With minimal information and constantly changing circumstances, nursing executives spearheaded change with leadership skills including a flexible approach, courageous decision-making and taking calculated risks. Opportunities for innovative work practices were taken, with nursing leading policy development and delivery of care models in new and established healthcare settings, supporting patient and staff safety. IMPACT: Nursing comprises the majority of the healthcare workforce, placing executive nurse leaders in a key role for healthcare responses to the COVID-19 pandemic. Nursing's contribution was multi-faceted, and advantages gained for nursing practice must be maintained and leveraged. Recommendations for how nursing can contribute to current and future widespread health emergencies are provided.

Smaller Cortisol Awakening Responses Are Associated with Greater Visual Dependence in Postural Control.

There are known links between the hypothalamic-pituitary-adrenal (HPA) axis and systems responsible for regulating posture. Our aim was to explore directly, for the first time, whether an aspect of circadian HPA axis activity (the cortisol awakening response: CAR) was associated with greater visual dependency in postural control. For measurement of the CAR, electronically monitored saliva samples were collected by participants following morning awakening in their home environment. On the afternoons of the same days, postural sway was measured in the laboratory by exposing participants to static (control) and moving visual stimuli whilst standing still and upright on a force platform. Visual dependence was assessed as the increase in postural sway (path length) during exposure to the moving compared with the static condition. The 44 measurement days were derived from four days for each of eleven healthy participants (mean ± SD age: 51.18 ± 3.3 years). As expected, postural sway was greater when exposed to moving versus static cues. Mixed regression modelling showed that participants with smaller four day average CARs had greater deterioration in postural sway when presented with moving stimuli. These data are the first to document associations between the CAR and visual dependency in postural sway.

Assessing the Effectiveness of Automated Emotion Recognition in Adults and Children for Clinical Investigation.

Recent success stories in automated object or face recognition, partly fuelled by deep learning artificial neural network (ANN) architectures, have led to the advancement of biometric research platforms and, to some extent, the resurrection of Artificial Intelligence (AI). In line with this general trend, inter-disciplinary approaches have been taken to automate the recognition of emotions in adults or children for the benefit of various applications, such as identification of children's emotions prior to a clinical investigation. Within this context, it turns out that automating emotion recognition is far from being straightforward, with several challenges arising for both science (e.g., methodology underpinned by psychology) and technology (e.g., the iMotions biometric research platform). In this paper, we present a methodology and experiment and some interesting findings, which raise the following research questions for the recognition of emotions and attention in humans: (a) the adequacy of well-established techniques such as the International Affective Picture System (IAPS), (b) the adequacy of state-of-the-art biometric research platforms, (c) the extent to which emotional responses may be different in children and adults. Our findings and first attempts to answer some of these research questions are based on a mixed sample of adults and children who took part in the experiment, resulting in a statistical analysis of numerous variables. These are related to both automatically and interactively captured responses of participants to a sample of IAPS pictures.

A Self-Compassion Group Intervention for Patients Living With Chronic Medical Illness: Treatment Development and Feasibility Study.

BACKGROUND: Self-compassion is a psychological skill associated with good mental health and adjustment to illness in the second half of life, but to date, few self-compassion-based interventions have been developed specifically for use in midlife and older adult cohorts. The purpose of this study was to develop and test the feasibility of a 4-week group self-compassion-based intervention designed to improve self-report and biological markers of well-being in midlife and older adult patients living with chronic illness. METHODS: Treatment development drew on existing literature, expert input, and qualitative interview data. Eight patients in outpatient treatment for a chronic illness were recruited from a rehabilitation hospital (during September and October 2017 and again during February and March 2018) to test feasibility. Participants attended a 1-hour group self-compassion-based intervention once per week for 4 weeks. Feasibility was assessed on 6 domains. Measures of well-being and heart rate variability (HRV), an index of nervous system functioning, were also collected. RESULTS: Recruitment was feasible and occurred within the expected time frame. Attendance at sessions was high (84.4%), with no dropouts. Participants found that the intervention was acceptable, rating sessions as enjoyable (6.8/7) and relevant to daily life (6.6/7). There were no adverse events. Secondary analysis revealed pre-post improvements for some well-being outcomes, such as a significant reduction in depressive symptoms (Hedges' g = -1.18, 95% CI, -0.18 to -2.16). CONCLUSIONS: A 4-session group self-compassion-based intervention was found to be feasible and acceptable to midlife and older adult patients in treatment for a chronic illness. A larger, randomized pilot trial is needed to explore the efficacy of this intervention. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) identifier: ACTRN12619000709145​.

Mechanism of Off-Target Interactions and Toxicity of Tamoxifen and Its Metabolites.

Tamoxifen is an estrogen modulator that acts to competitively inhibit the binding of endogenous estrogens. It is widely used for treatment of breast cancer; however, analogous with many antineoplastic agents, tamoxifen is associated with numerous adverse effects, most prominently nausea. We have identified several off-target receptors of tamoxifen and 22 of its metabolites that include histamine H1 and H3, and muscarinic M1, M4, and M5 subtypes, and dopamine D2 receptor. We have shown how they are associated with tamoxifen and its metabolites' toxicity through a comprehensive computational analysis of their interaction modes, which were also compared to that of the related endogenous substrates of each receptor. The results were further evaluated using available in vivo and in vitro data. The presented work provides foundational knowledge toward the determination of the precise mechanism of nausea induction, and in particular, interactions of tamoxifen and its metabolites with the receptors involved in that biomolecular pathway. This study can assist in predicting the potential undesired effects of the chemicals with common pharmacophores or similar fragments to that of tamoxifen and its metabolites and serve drug discovery research in developing more effective and tolerable tamoxifen analogues or chemotherapeutic agents.

Visual mismatch negativity to masked stimuli presented at very brief presentation rates.

Mismatch negativity (MMN) has been characterised as a 'pre-attentive' component of an event-related potential (ERP) that is related to discrimination and error prediction processes. The aim of the current experiment was to establish whether visual MMN could be recorded to briefly presented, backward and forward masked visual stimuli, given both below and above levels of subjective experience. Evidence of visual MMN elicitation in the absence of the ability to consciously report stimuli would provide strong evidence for the automaticity of the visual MMN mechanism. Using an oddball paradigm, two stimuli that differed in orientation from each other, a + and an ×, were presented on a computer screen. Electroencephalogram (EEG) was recorded from nine participants (six females), mean age 21.4 years. Results showed that for stimuli that were effectively masked at 7 ms presentation, there was little variation in the ERPs evoked to standard and deviant stimuli or in the subtraction waveform employed to delineate the visual MMN. At 14 ms stimulus presentation, when participants were able to report stimulus presence, an enhanced negativity at around 175 and 305 ms was observed to the deviant and was evident in the subtraction waveform. However, some of the difference observed in the ERPs can be attributed to stimulus characteristics, as the use of a 'lonely' deviant protocol revealed attenuated visual MMN components at 14 ms stimulus presentation. Overall, results suggest that some degree of conscious attention is required before visual MMN components emerge, suggesting visual MMN is not an entirely pre-attentive process.

Human T-Lymphotropic Virus type 1 infection in an Indigenous Australian population: epidemiological insights from a hospital-based cohort study.

BACKGROUND: The Human T Lymphotropic Virus type 1 (HTLV-1) subtype C is endemic to central Australia where each of the major sequelae of HTLV-1 infection has been documented in the socially disadvantaged Indigenous population. Nevertheless, available epidemiological information relating to HTLV-1c infection is very limited, risk factors for transmission are unknown and no coordinated program has been implemented to reduce transmission among Indigenous Australians. Identifying risk factors for HTLV-1 infection is essential to direct strategies that could control HTLV-1 transmission. METHODS: Risk factors for HTLV-1 infection were retrospectively determined for a cohort of Indigenous Australians who were tested for HTLV-1 at Alice Springs Hospital (ASH), 1st January 2000 to 30th June 2013. Demographic details were obtained from the ASH patient management database and the results of tests for sexually transmitted infections (STI) were obtained from the ASH pathology database. RESULTS: Among 1889 Indigenous patients whose HTLV-1 serostatus was known, 635 (33.6 %) were HTLV-1 Western blot positive. Only one of 77 (1.3 %) children tested was HTLV-1 infected. Thereafter, rates progressively increased with age (15-29 years, 17.3 %; 30-49 years, 36.2 %; 50-64 years, 41.7 %) reaching 48.5 % among men aged 50-64 years. In a multivariable model, increasing age (OR, 1.04; 95 % CI, 1.03-1.04), male gender (OR, 1.41; 95 % CI, 1.08-1.85), residence in the south (OR, 10.7; 95 % CI, 7.4-15.6) or west (OR, 4.4; 95 % CI, 3.1-6.3) of central Australia and previous STI (OR, 1.42; 95 % CI, 1.04-1.95) were associated with HTLV-1 infection. Infection was acquired by three of 351 adults who were tested more than once during the study period (seroconversion rate, 0.24 (95 % CI = 0.18-2.48) per 100 person-years). CONCLUSIONS: This study confirms that HTLV-1 is highly endemic to central Australia. Although childhood infection was documented, HTLV-1 infection in adults was closely associated with increasing age, male gender and STI history. Multiple modes of transmission are therefore likely to contribute to high rates of HTLV-1 infection in the Indigenous Australian population. Future strategies to control HTLV-1 transmission in this population require careful community engagement, cultural understanding and Indigenous leadership.

Observed bodies generate object-based spatial codes.

Contemporary studies of spatial and social cognition frequently use human figures as stimuli. The interpretation of such studies may be complicated by spatial compatibility effects that emerge when researchers employ spatial responses, and participants spontaneously code spatial relationships about an observed body. Yet, the nature of these spatial codes - whether they are location- or object-based, and coded from the perspective of the observer or the figure - has not been determined. Here, we investigated this issue by exploring spatial compatibility effects arising for objects held by a visually presented whole-bodied schematic human figure. In three experiments, participants responded to the colour of the object held in the figure's left or right hand, using left or right key presses. Left-right compatibility effects were found relative to the participant's egocentric perspective, rather than the figure's. These effects occurred even when the figure was rotated by 90° to the left or to the right, and the coloured objects were aligned with the participant's midline. These findings are consistent with spontaneous spatial coding from the participant's perspective and relative to the normal upright orientation of the body. This evidence for object-based spatial coding implies that the domain general cognitive mechanisms that result in spatial compatibility effects may contribute to certain spatial perspective-taking and social cognition phenomena.

Care, compassion and competence in critical care: a qualitative exploration of nurses' experience of family witnessed resuscitation.

This exploratory study was grounded in a local initiative promoting family witnessed resuscitation in the critical care units of a regional cardio-thoracic centre in the United Kingdom (UK). Research in this field has focussed on the perceived benefits, or otherwise, of family involvement, but little is known about the impact this has on critical care nurses or their practice. This study aimed to gain insights into nurses' experience of family witnessed resuscitation and identify any implications for critical care practices. The study employed a phenomenological approach and interviewed six nurses who had been involved in family witnessed resuscitation. Data from the transcribed interviews were analysed thematically and organised into descriptive categories which reflected the nursing experience of these resuscitation events. The three thematic categories generated by data analysis illustrate the challenges nurses faced in seeking to balance compassionate care and technical competence in emergency situations on critical care units. They also showed how nurses sought to reconcile unsettling emotions with their professional practice and responsibilities. The findings of this study are consistent with what is already known about the challenges of critical care nursing, but suggest that more research is needed to understand the practical and emotional complexities of family witnessed resuscitation.

Searching for the new normal: exploring the role of language and metaphors in becoming a cancer survivor.

PURPOSE: This qualitative exploratory study was grounded in local patient and service user experiences and was designed to investigate how the language and metaphors of cancer influence personal and social adjustment after completion of a course of treatment. METHODS: The study employed a focus group design, in which eighteen people, recruited through regional networks and support groups, participated. Meetings elicited participants' stories and focused discussion on key words and common phrases in the cancer lexicon. Data from transcribed focus group recordings were analysed thematically and organised into descriptive categories concerned with the interpretations of common terms and how these influenced the management of identity and emotions. RESULTS: The thematic categories emphasised the importance of language in the way participants managed their illness and sought to control their feelings and their interactions with others. Interpretation of findings revealed a strong central idea linking participants' accounts, which was that language, metaphor and euphemism are central to adjustment and the forging of an altered identity as a survivor of cancer diagnosis and treatment. CONCLUSIONS: The findings are consistent with what is already known about the language and metaphors of cancer, with language being an important mechanism for managing uncertainty. From participants' accounts it also appears that there may be subtle but important differences in professional and lay understandings of cancer language and metaphor. This suggests a need for oncology nurses to elaborate their broad understanding of communication skills and move toward a more detailed understanding of the language used during interactions with patients.

A review of the efficacy of neuromuscular electrical stimulation in critically ill patients.

BACKGROUND: Muscle wasting in critical illness has been identified as a major clinical concern which can lead to persistent muscle weakness, impede recovery and limit physical function and quality of life in survivors. Neuromuscular electrical stimulation (NMES) has been suggested as an alternative to active exercise in critically ill patients. OBJECTIVES: To evaluate the efficacy of NMES in critically ill patients by evaluating the research literature. METHODS: Structured database searches of the Cochrane Library, Ovid (Medline), CINHAL, Scopus and PEDro were completed. RESULTS: Eight papers were retrieved and methodological quality evaluated using the Critical Appraisal and Skills Program tool. The NMES protocols, outcomes and findings were analysed and, given the methodological heterogeneity, the study findings were synthesised as a narrative. Analysis showed minimal adverse effects in the use of NMES and some potential benefits of NMES on preservation of muscle strength, decreased duration of mechanical ventilation and shorter Intensive Care Unit (ICU) length of stay. CONCLUSIONS: Evidence of the clinical benefits of NMES in the ICU is inconclusive and provides minimal guidance for use in clinical practice. There is a need for further research in this area.

Is compassion possible in a market-led NHS?

The principle of compassionate care is increasingly seen as the core element of good nursing practice. However, recent media reports have focused on the "compassion deficit". We carried out a review of national and international evidence on core professional values, which showed that caring and compassion are inherent nursing values. While the development of these values is influenced by training and role modelling, the main influence is the organisation and culture in which nurses work. This article discusses the findings of the review in relation to the national debate around compassionate care within an NHS that is being fundamentally changed. We suggest any failure in compassion is more likely to be due to government health policy and NHS organisational culture than to any shortcomings of nurses or nursing practice.

Management of anaphylaxis in the ED: a clinical audit.

Anaphylaxis is one of the potentially life threatening conditions which present to the ED however there is no universal understanding or definitive diagnostic test to aid ED practitioners in its management. Evidence suggests this leads to confusion for ED staff and may compromise patient care. This paper reviews the existing evidence around the effective diagnosis, emergency treatment and long term management of anaphylaxis. It then describes a clinical audit which was carried out in the ED of a large UK University hospital. A retrospective audit design sampled all patients presenting with anaphylaxis in one calendar year, 146 cases were eligible for inclusion. The audit results were consistent with the existing understanding and showed widespread inconsistencies in the diagnosis and treatment of this patient group. The implications the findings may have for the wider ED nursing community are discussed and we conclude that further research and service development is needed to ensure the best possible care for patients with anaphylaxis.

Empathic and non-empathic routes to visuospatial perspective-taking.

The present study examined whether strategy moderated the relationship between visuospatial perspective-taking and empathy. Participants (N=96) undertook both a perspective-taking task requiring speeded spatial judgements made from the perspective of an observed figure and the Empathy Quotient questionnaire, a measure of trait empathy. Perspective-taking performance was found to be related to empathy in that more empathic individuals showed facilitated performance particularly for figures sharing their own spatial orientation. This relationship was restricted to participants that reported perspective-taking by mentally transforming their spatial orientation to align with that of the figure; it was absent in those adopting an alternative strategy of transposing left and right whenever confronted with a front-view figure. Our finding that strategy moderates the relationship between empathy and visuospatial perspective-taking enables a reconciliation of the apparently inconclusive findings of previous studies and provides evidence for functionally dissociable empathic and non-empathic routes to visuospatial perspective-taking.

Quality assurance of nursing web sites: development and implications of the ALEU method.

This article presents a study that evaluated the physical accessibility, readability, and usability of Spanish nursing Web sites and discusses the quality assurance issues raised, which are relevant to the wider nursing community. The Internet is recognized as an important source of health information for both nurses and the general public. Although it makes health-related information universally available, the wide variation in the overall quality of health Web sites is problematic. This raises many questions for the nursing profession: about what constitutes a good-quality Web site, about the nature of the information that nurses are finding and using to support their professional education, research, and clinical practice, and about the impact that Internet information ultimately has on health interactions and nursing care. The process of completing this small study showed that it is possible to usefully assess dimensions of Web site quality and suggested that it may be feasible to develop tools to help nurses evaluate national and international nursing Web sites. More research is needed to understand how nurses use the Internet to support their everyday professional practices, but the development and application of international Web site quality assurance tools may be important for maintaining professional nursing standards in the Internet age.

A review of pain management interventions in bone marrow biopsy.

AIMS: This review was designed to evaluate the evidence relating to pain management interventions for patients having bone marrow biopsy. BACKGROUND: Bone marrow biopsy is an invasive procedure causing considerable pain and anxiety for adult patients, yet there are no guidelines to inform effective nursing care. Although this is an under-researched area, a range of pain interventions have been tested on this patient group, but this evidence has not been synthesised. DESIGN: Structured evidence review. METHOD: The Cochrane Library and databases Medline, Scopus and Cinahl were searched for original research reports. Reference lists of retrieved papers were hand-searched and researchers in the field were contacted. Retrieved papers were analysed using the CASP framework. A narrative data synthesis considered the strengths and limitations of included studies and findings were collated and interpreted. RESULTS: No systematic reviews of evidence have been undertaken and the search strategy identified twelve research studies eligible for inclusion in the review. Hand-searching did not identify any additional studies, and emails to researchers confirmed this is an under-researched field. Analysis shows three main interventions, intravenous midazolam, premedication with analgesia and/or anxiolysis and the use of Entonox™ are used to manage the pain experience for patients undergoing a bone marrow biopsy. CONCLUSIONS: Evidence is inconclusive and provides little guidance for practice. There is an urgent need for research into effective interventions for pain management in bone marrow biopsy and in understanding the patient experience. RELEVANCE TO CLINICAL PRACTICE: Nurses have a central role to play in the assessment and management of the pain and anxiety associated with bone marrow biopsy. There is little evidence to guide this aspect of care, but it is important that nurses involved with bone marrow biopsy are aware of the best evidence to facilitate the most effective management of their patients' pain.

Using the prone position for ventilated patients with respiratory failure: a review.

AIMS: this review explored the evidence relating to prone positioning in ventilated patients diagnosed with respiratory failure, including acute lung injury (ALI) or adult respiratory distress syndrome (ARDS). BACKGROUND: mortality rates for ventilated patients with ALI or ARDS are high, and there is a growing body of evidence suggesting that the position these patients are nursed in may influence clinical outcomes. However, there are no guidelines to inform nursing practice in positioning these patients. METHOD: Medline, Scopus, Cinahl and the Cochrane Library databases were searched for original research reports or systematic reviews of evidence between 2000 and 2009. Reference lists of retrieved papers were hand searched and included studies were analysed using the Critical Appraisal and Skills Programme framework. A narrative data synthesis considered the strengths and limitations of studies, and findings were collated and interpreted. RESULTS: Application of the search strategy identified a systematic review, currently underway, which has not yet reported and 14 relevant studies eligible for inclusion in this review. Analysis showed considerable variation in study design, but suggests that PaO(2) /FiO(2) ratio, incidence of VAP and mortality may be positively affected by prone positioning. CONCLUSIONS: evidence of the clinical benefits associated with prone positioning is inconclusive and provides little guidance for nursing practice. There is a need for further research into the clinical outcomes of prone positioning, and greater understanding of the practicalities of prone positioning critically ill patients is required. RELEVANCE TO CLINICAL PRACTICE: nurses have a central role to play in the continual assessment and management of this patient group, including the position they are nursed in, not only to ensure the best clinical outcomes but also to provide care and comfort to the patient and their family. It is therefore important that their nursing practice and interventions are informed by the best available evidence.