Maori end-of-life care in the intensive care unit: A qualitative exploration of nursing perspectives.

BACKGROUND: Although goals of care for intensive care patients are typically focussed on restoration of health, 8-15% of patients will die in the intensive care unit (ICU), or soon after transfer to a ward. Early recognition of the need for end-of-life care is vital to identify and support the wishes of the patient and needs of their family. In Aotearoa, New Zealand, Maori are over-represented in admissions to ICUs. Enabling nursing staff to provide culturally safe care to Maori patients and whanau (family, including extended family, kin) at the end of life is critical to upholding Te Tiriti o Waitangi requirements and providing equitable care. This qualitative study explores the experiences of both Maori and non-Maori intensive care nurses, in providing end-of-life care for Maori patients and their whanau. OBJECTIVES: The objective of this study was to characterise nursing experiences of end-of-life care for Maori in the ICU, identify barriers to and facilitators of confident, competent culturally responsive care, and highlight opportunities to improve preparation and support. METHODS: Qualitative semistructured interviews were undertaken with nine intensive care nurses (four Maori and five non-Maori) with experience ranging from novice to expert. Data collection and analysis was underpinned by reflexive thematic analysis strengthened by Kaupapa Maori Research values and tikanga best practice. FINDINGS: Participants described positive and negative experiences in caring for Maori at the end of life. Culturally responsive end-of-life care for Maori in intensive care appears dependent on the acknowledgement and inclusion of whanau as members of the multidisciplinary team. Participants identified a need for high-quality education, supportive unit end-of-life care guidelines and hospital policies, and cultural resources to confidently provide quality end-of-life care. CONCLUSION: Improved understanding of Maori culture, critical awareness of systems of power and privilege, and the availability of cultural liaisons may increase the confidence and competence of ICU nurses providing care to Maori whanau.

Embedding LGBTQI+ competency into nursing education: Formative evaluation of an interdisciplinary project.

BACKGROUND: In order to avoid perpetuating inequities faced by lesbian, gay, bisexual, transgender, queer, intersex, and other minority (LGBTQI+) communities, future nurses need to recognize and resist discriminatory, oppressive, heteronormative and cisnormative health and social systems. OBJECTIVES: To share the development, embedding, and formative evaluation of an interdisciplinary project to improve LGBTQI+ health content across an undergraduate nursing curriculum. METHODS: This paper describes a collaborative interdisciplinary project to embed LGBTQI+ health content across a 3-year undergraduate nursing degree. An anonymous cross-sectional online survey was sent to 87 student nurses enrolled in the final semester of their undergraduate degree. The survey included six Likert scale-type questions and five open-ended questions. Qualitative data were analyzed by inductive, reflexive thematic analysis. RESULTS: Most students rated the topic relevant 'extremely' relevant (77 %) to nursing. Students' self-reported comfort discussing LGBTQI+ health in class varied from 'extremely' (42 %) through to 'not at all' (6 %). Thematic analysis of student responses to open-ended questions identified five themes: (1) Becoming aware of LGBTQI+ diversity; (2) Personal values and beliefs; (3) Learning in order to improve clinical encounters; (4) Inconsistency and a lack of incorporation across the curriculum; and (5) (Dis)comfort in the learning environment. CONCLUSIONS: Opportunities to better embed LGBTQI+ competency included clear acknowledgement of wider systems of power and oppression, integration and consistent modeling by nursing faculty, and linkage of content to other equity issues to address the intersectional nature of inequities.

Palliative paramedicine: Comparing clinical practice through guideline quality appraisal and qualitative content analysis.

BACKGROUND: Palliative care is an emerging scope of practice for paramedicine. The COVID-19 pandemic has highlighted the opportunity for emergency settings to deliver palliative and end-of-life care to patients wishing to avoid intensive life-sustaining treatment. However, a gap remains in understanding the scope and limitations of current ambulance services' approach to palliative and end-of-life care. AIM: To examine the quality and content of existing Australian palliative paramedicine guidelines with a sample of guidelines from comparable Anglo-American ambulance services. DESIGN: We appraised guideline quality using the AGREE II instrument and employed a collaborative qualitative approach to analyse the content of the guidelines. DATA SOURCES: Eight palliative care ambulance service clinical practice guidelines (five Australian; one New Zealand; one Canadian; one United Kingdom). RESULTS: None of the guidelines were recommended by both appraisers for use based on the outcomes of all AGREE II evaluations. Scaled individual domain percentage scores varied across the guidelines: scope and purpose (8%-92%), stakeholder involvement (14%-53%), rigour of development (0%-20%), clarity of presentation (39%-92%), applicability (2%-38%) and editorial independence (0%-38%). Six themes were developed from the content analysis: (1) audience and approach; (2) communication is key; (3) assessing and managing symptoms; (4) looking beyond pharmaceuticals; (5) seeking support; and (6) care after death. CONCLUSIONS: It is important that ambulance services' palliative and end-of-life care guidelines are evidence-based and fit for purpose. Future research should explore the experiences and perspectives of key palliative paramedicine stakeholders. Future guidelines should consider emerging evidence and be methodologically guided by AGREE II criteria.

A Qualitative Study on the Experiences of Women With Breast Implant Illness.

BACKGROUND: Breast implant illness (BII) is a term used to describe physical and psychological symptoms experienced by some women following breast implant surgery. Few studies have examined the experiences of women with BII-a poorly understood condition with no clear cause or treatment. OBJECTIVES: The aim of this study was to explore women's experiences of BII, including symptoms, healthcare encounters, social media, and explant surgery. METHODS: Employing an exploratory qualitative methodology, researchers undertook semistructured interviews with 29 women who self-identified as having BII. Interviews were audio-recorded and transcribed verbatim. Data were analyzed by inductive thematic analysis. RESULTS: Thematic analysis of the interviews identified 6 themes: (1) symptoms without explanation; (2) invalidation and invisibility; (3) making the BII connection; (4) implant toxicity; (5) explant surgery: solution to suffering?; and (6) concealed information. BII was described as distressing and debilitating across multiple domains including relationships, work, identity, and physical and mental health, and symptoms were attributed to implant toxicity and immune system rejection of foreign objects. When their experience was not validated by healthcare professionals, many looked to social media for information, support, and understanding, and saw explant as their only chance of recovery. CONCLUSIONS: BII is disabling mentally and physically. Women with BII require support, understanding, and validation, and proactive treatment to prevent disability. With unclear pathophysiology, future research should examine how biopsychosocial approaches can be used to guide treatment, and how to best support women with BII, focusing on early detection and evidence-based education and intervention.

Prehospital Resuscitation Decision Making: A model of ambulance personnel experiences, preparation and support.

OBJECTIVE: This paper presents the first Naturalistic Decision Making model of prehospital resuscitation decision-making, which has clear implications for education, practice and support. METHODS: A mixed-methods exploratory sequential research design consisting of interviews with ambulance personnel (study 1), focus groups with ambulance educators, managers and peer supporters (study 2), and an online survey of graduating paramedic students (study 3). This paper reports the model developed from integrated findings, across all three studies. All research was undertaken in New Zealand and underpinned by a critical realist worldview. RESULTS: The Prehospital Resuscitation Decision Making model identifies key processes, challenges and facilitators before, during and after ambulance personnel attend a cardiac arrest event. It is the only descriptive model of resuscitation decision making which acknowledges the decision-maker, non-prognostic factors and the importance of adequate preparation and support. CONCLUSIONS: This research project is the first to comprehensively explore and model ambulance personnel perspectives on decisions to start, continue or stop resuscitation. The decision-making process is complex and difficult to simply formularise. Education and supports must assist ambulance personnel in navigating this complexity. Where resuscitation is withheld or terminated, ambulance personnel need to feel confident that they can effectively provide after-death care.

Commence, continue, withhold or terminate?: a systematic review of decision-making in out-of-hospital cardiac arrest.

When faced with an out-of-hospital cardiac arrest patient, prehospital and emergency resuscitation providers have to decide when to commence, continue, withhold or terminate resuscitation efforts. Such decisions may be made difficult by incomplete information, clinical, resourcing or scene challenges and ethical dilemmas. This systematic integrative review identifies all research papers examining resuscitation providers' perspectives on resuscitation decision-making for out-of-hospital cardiac arrest patients. A total of 14 studies fulfilled the inclusion criteria: nine quantitative, four qualitative and one mixed-methods design. Five themes were identified, describing factors informing resuscitation provider decision-making: the arrest event; patient characteristics; the resuscitation scene; resuscitation provider perspectives; and medicolegal concerns. Established prognostic factors are generally considered important, but there is a lack of resuscitation provider consensus on other factors, indicating that decision-making is influenced by the perspective of resuscitation providers themselves. Resuscitation decision-making research typically draws conclusions from evaluation of cardiac arrest registry data or clinical notes, but these may not capture all salient factors. Future research should explore resuscitation provider perspectives to better understand these important decisions and the clinical, ethical, emotional and cognitive demands placed on resuscitation providers.

How free of germs is germ-free? Detection of bacterial contamination in a germ free mouse unit.

Management of germ free animals has changed little since the beginning of the 20th century. The current upswing in their use, however, has led to interest in improved methods of screening and housing. Traditionally, germ free colonies are screened for bacterial colonization by culture and examination of Gram stained fecal samples, but some investigators have reported using PCR-based methods of microbial detection, presumably because of perceived increased sensitivity. The accuracy and detection limit for traditional compared to PCR-based screening assays are not known. The purpose of this study was to determine the limit of detection of bacterial contamination of mouse feces by aerobic and anaerobic culture, Gram stain, and qPCR, and to compare the accuracy of these tests in the context of a working germ free mouse colony. We found that the limit of detection for qPCR (approximately 10(5) cfu/g of feces) was lower than for Gram stain (approximately 10(9) cfu/g), but that all 3 assays were of similar accuracy. Bacterial culture was the most sensitive, but the least specific, and qPCR was the least sensitive and most specific. Gram stain but not qPCR detected heat-killed bacteria, indicating that bacteria in autoclaved diet are unlikely to represent a potential confounding factor for PCR screening. We conclude that as a practical matter, bacterial culture and Gram stain are adequate for screening germ free mouse colonies for bacterial contaminants, but that should low numbers of unculturable bacteria be present, they would not be detected with any of the currently available means.

Treating retinoblastoma in tissue culture and in a rat model with a novel isoquinoline derivative.

PURPOSE. To investigate the effectiveness of a novel isoquinoline derivative, EDL-155, in killing retinoblastoma in vitro and in vivo. METHODS. Dose-response curves were generated in which Y79 retinoblastoma cells tagged with luciferase (Y79-Luc) were treated with serial concentrations of EDL-155. Electron microscopy was used to evaluate the ultrastructural morphology of EDL-155-treated Y79 cells. To determine whether autophagy was induced in EDL-155-treated Y79-Luc cells, staining with acridine orange and LC-3 immunoblot analysis was performed. To evaluate the efficacy of EDL-155 in vivo, Y79-Luc retinoblastoma cells were injected into the vitreous cavity of newborn rats, followed by periocular injections of EDL-155 (20 mg/kg/day) or an equivalent dosage of saline. RESULTS. EDL-155 appeared to destroy the retinoblastoma cells in vitro with an EC(50) of 9.1 micriM. EDL-155-treated retinoblastoma cells displayed a lack of viable mitochondria and the presence of autophagosomes wrapped in the characteristic double membranes. Acridine orange staining of EDL-155-treated retinoblastoma cells demonstrated the accumulation of vacuoles, and the immunoblots displayed a shift in molecular weight of LC-3, indicative of incorporation into autophagosome vesicles. In the retinoblastoma animal model, four doses of EDL-155 were delivered over 4 days, which was sufficient to see a significant decrease (P = 0.01) in viable intraocular tumors. Seven of the 25 rats treated with EDL-155 had no detectable living tumor. No significant decrease in viable tumor was observed in control animals. CONCLUSIONS. EDL-155 appears to eliminate retinoblastoma cells by disrupting mitochondria and inducing autophagy. Local delivery of EDL-155 may be an effective therapy for some types of ocular cancers.

Gene expression in the mouse eye: an online resource for genetics using 103 strains of mice.

PURPOSE: Individual differences in patterns of gene expression account for much of the diversity of ocular phenotypes and variation in disease risk. We examined the causes of expression differences, and in their linkage to sequence variants, functional differences, and ocular pathophysiology. METHODS: mRNAs from young adult eyes were hybridized to oligomer microarrays (Affymetrix M430v2). Data were embedded in GeneNetwork with millions of single nucleotide polymorphisms, custom array annotation, and information on complementary cellular, functional, and behavioral traits. The data include male and female samples from 28 common strains, 68 BXD recombinant inbred lines, as well as several mutants and knockouts. RESULTS: We provide a fully integrated resource to map, graph, analyze, and test causes and correlations of differences in gene expression in the eye. Covariance in mRNA expression can be used to infer gene function, extract signatures for different cells or tissues, to define molecular networks, and to map quantitative trait loci that produce expression differences. These data can also be used to connect disease phenotypes with sequence variants. We demonstrate that variation in rhodopsin expression efficiently predicts candidate genes for eight uncloned retinal diseases, including WDR17 for the human RP29 locus. CONCLUSIONS: The high level of strain variation in gene expression is a powerful tool that can be used to explore and test molecular networks underlying variation in structure, function, and disease susceptibility. The integration of these data into GeneNetwork provides users with a workbench to test linkages between sequence differences and eye structure and function.

Differential response of C57BL/6J mouse and DBA/2J mouse to optic nerve crush.

BACKGROUND: Retinal ganglion cell (RGC) death is the final consequence of many blinding diseases, where there is considerable variation in the time course and severity of RGC loss. Indeed, this process appears to be influenced by a wide variety of genetic and environmental factors. In this study we explored the genetic basis for differences in ganglion cell death in two inbred strains of mice. RESULTS: We found that RGCs are more susceptible to death following optic nerve crush in C57BL/6J mice (54% survival) than in DBA/2J mice (62% survival). Using the Illumina Mouse-6 microarray, we identified 1,580 genes with significant change in expression following optic nerve crush in these two strains of mice. Our analysis of the changes occurring after optic nerve crush demonstrated that the greatest amount of change (44% of the variance) was due to the injury itself. This included changes associated with ganglion cell death, reactive gliosis, and abortive regeneration. The second pattern of gene changes (23% of the variance) was primarily related to differences in gene expressions observed between the C57BL/6J and DBA/2J mouse strains. The remaining changes in gene expression represent interactions between the effects of optic nerve crush and the genetic background of the mouse. We extracted one genetic network from this dataset that appears to be related to tissue remodeling. One of the most intriguing sets of changes included members of the crystallin family of genes, which may represent a signature of pathways modulating the susceptibility of cells to death. CONCLUSION: Differential responses to optic nerve crush between two widely used strains of mice were used to define molecular networks associated with ganglion cell death and reactive gliosis. These results form the basis for our continuing interest in the modifiers of retinal injury.

Expression of the Arf tumor suppressor gene is controlled by Tgfbeta2 during development.

The Arf tumor suppressor (also known as Cdkn2a) acts as an oncogene sensor induced by ;abnormal' mitogenic signals in incipient cancer cells. It also plays a crucial role in embryonic development: newborn mice lacking Arf are blind due to a pathological process resembling severe persistent hyperplastic primary vitreous (PHPV), a human eye disease. The cell-intrinsic mechanism implied in the oncogene sensor model seems unlikely to explain Arf regulation during embryo development. Instead, transforming growth factor beta2 (Tgfbeta2) might control Arf expression, as we show that mice lacking Tgfbeta2 have primary vitreous hyperplasia similar to Arf(-/-) mice. Consistent with a potential linear pathway, Tgfbeta2 induces Arf transcription and p19(Arf) expression in cultured mouse embryo fibroblasts (MEFs); and Tgfbeta2-dependent cell cycle arrest in MEFs is maintained in an Arf-dependent manner. Using a new model in which Arf expression can be tracked by beta-galactosidase activity in Arf(lacZ/+) mice, we show that Tgfbeta2 is required for Arf transcription in the developing vitreous as well as in the cornea and the umbilical arteries, two previously unrecognized sites of Arf expression. Chemical and genetic strategies show that Arf promoter induction depends on Tgfbeta receptor activation of Smad proteins; the induction correlates with Smad2 phosphorylation in MEFs and Arf-expressing cells in vivo. Chromatin immunoprecipitation shows that Smads bind to genomic DNA proximal to Arf exon 1beta. In summary, Tgfbeta2 and p19(Arf) act in a linear pathway during embryonic development. We present the first evidence that p19(Arf) expression can be coupled to extracellular cues in normal cells and suggest a new mechanism for Arf control in tumor cells.

Cannabinoid (CB2) receptor deficiency reduces the susceptibility of macrophages to oxidized LDL/oxysterol-induced apoptosis.

Macrophage apoptosis is an important process in the pathophysiology of atherosclerosis. Oxidized low-density lipoproteins (OxLDL) are a major component of lesions and potently induce macrophage apoptosis. Cannabinoid receptor 2 (CB2), the predominant macrophage cannabinoid receptor, modulates several macrophage processes associated with ongoing atherosclerosis; however, the role of CB2 in macrophage apoptosis is unknown. To determine if CB2 influences a macrophage apoptotic pathway relevant to atherosclerosis, we examined the effect of CB2 deficiency on OxLDL-induced macrophage apoptosis. In situ terminal transferase-mediated dUTP nick end labeling (TUNEL) analysis of resident peritoneal macrophages detected significantly fewer apoptotic CB2(-/-) macrophages than CB2(+/+) macrophages after incubation with OxLDL (27.9 +/- 4.7% vs. 61.9 +/- 8.5%, P < 0.001) or 7-ketocholesterol (7KC) (18.9 +/- 10.5% vs. 54.1 +/- 6.9%, P < 0.001), an oxysterol component of OxLDL. Caspase-3 activity; proteolytic conversion of procaspase-3; and cleavage of a caspase-3 substrate, PARP, were also diminished in 7KC-treated CB2(-/-) macrophages. Furthermore, the deactivation of the prosurvival kinase, Akt, in response to 7KC was impaired in CB2(-/-) macrophages. These results suggest that CB2 expression increases the susceptibility of macrophages to OxLDL-induced apoptosis, in part, by modulating the effect of oxysterols on the Akt survival pathway and that CB2 may influence atherosclerosis by modulating lesional macrophage apoptosis.