Paediatric death and dying: Exploring coping strategies of health professionals and perceptions of support provision

Without question a child’s death is a devastating event for parents and their families. Health professionals working with the dying child and family draw upon their expertise and experience to engage with children, parents, and families on this painful journey. A delicate and sensitive area of practice, it has strong and penetrating effects on health professionals. They employ physical, emotional, spiritual and problem solving strategies to continue to perform this role effectively and to protect their continued sense of well-being. Aim To explore health professionals’ perceptions of bereavement support surrounding the loss of a child. Methods The research was underpinned by social constructionism. Semi-structured interviews were held with 10 health professionals including doctors, nurses and social workers who were directly involved in the care of the dying child and family in 7 cases of paediatric death. Health professional narratives were analysed consistent with Charmarz’s (2006) approach. Results For health professionals, constructions around coping emerged as peer support, personal coping strategies, family support, physical impact of support and spiritual beliefs . Analysis of the narratives also revealed health professionals’ perceptions of their support provision. Conclusion Health professionals involved in caring for dying children and their families use a variety of strategies to cope with the emotional and physical toll of providing support. They also engage in self-assessment to evaluate their support provision and this highlights the need for self-evaluation tools in paediatric palliative care.

South Asians' cardiac medication adherence

Aim This paper is a report of a narrative review examining the current state of knowledge regarding adherence with cardiac medication among South Asian cardiac patients. Background South Asians experience higher rates of cardiovascular disease than any other ethnic group. South Asians may be less adherent with a cardiac medication regimen than Caucasians. The factors contributing to adherence are important to discover to assist South Asians to optimize their cardiac health. Data sources CINAHL, Medline (Ovid), PsychINFO, EMB Reviews-(Cochrane), and EMBASE were accessed using the key words: 'South Asian', 'Asia', 'East India', 'India', 'Pakistan', 'Bangladesh', 'Sri Lanka', 'medication compliance', 'medication noncompliance' and 'medication adherence'. English language papers published from January 1980 to January 2013 were eligible for inclusion. Review methods Abstracts were reviewed for redundancy and eligibility by the primary author. Manuscripts were then retrieved and reviewed for eligibility and validity by the first and last authors. Content analysis strategies were used for the synthesis. Results Thirteen papers were in the final data set; most were conducted in India and Pakistan. Medication side-effects, cost, forgetfulness and higher frequency of dosing contributed to non-adherence. South Asian immigrants also faced language barriers, which contributed to non-adherence. Knowledge regarding the medications prescribed was a factor that increased adherence. Conclusion South Asians' non-adherence to cardiac medications is multifaceted. How South Asians who newly immigrate to Western countries make decisions regarding their cardiac medication adherence ought to be explored in greater detail.

Gamma tocotrienol targets tyrosine phosphatase SHP2 in mammospheres resulting in cell death through RAS/ERK pathway

Background There is increasing evidence supporting the concept of cancer stem cells (CSCs), which are responsible for the initiation, growth and metastasis of tumors. CSCs are thus considered the target for future cancer therapies. To achieve this goal, identifying potential therapeutic targets for CSCs is essential. Methods We used a natural product of vitamin E, gamma tocotrienol (gamma-T3), to treat mammospheres and spheres from colon and cervical cancers. Western blotting and real-time RT-PCR were employed to identify the gene and protein targets of gamma-T3 in mammospheres. Results We found that mammosphere growth was inhibited in a dose dependent manner, with total inhibition at high doses. Gamma-T3 also inhibited sphere growth in two other human epithelial cancers, colon and cervix. Our results suggested that both Src homology 2 domain-containing phosphatase 1 (SHP1) and 2 (SHP2) were affected by gamma-T3 which was accompanied by a decrease in K- and H-Ras gene expression and phosphorylated ERK protein levels in a dose dependent way. In contrast, expression of self-renewal genes TGF-beta and LIF, as well as ESR signal pathways were not affected by the treatment. These results suggest that gamma-T3 specifically targets SHP2 and the RAS/ERK signaling pathway. Conclusions SHP1 and SHP2 are potential therapeutic targets for breast CSCs and gamma-T3 is a promising natural drug for future breast cancer therapy.

Strain- and host species-specific inflammasome activation, IL-1β release, and cell death in macrophages infected with uropathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC) is the main etiological agent of urinary tract infections (UTIs). Little is known about interactions between UPEC and the inflammasome, a key innate immune pathway. Here we show that UPEC strains CFT073 and UTI89 trigger inflammasome activation and lytic cell death in human macrophages. Several other UPEC strains, including two multidrug-resistant ST131 isolates, did not kill macrophages. In mouse macrophages, UTI89 triggered cell death only at a high multiplicity of infection, and CFT073-mediated inflammasome responses were completely NLRP3-dependent. Surprisingly, CFT073- and UTI89-mediated responses only partially depended on NLRP3 in human macrophages. In these cells, NLRP3 was required for interleukin-1β (IL-1β) maturation, but contributed only marginally to cell death. Similarly, caspase-1 inhibition did not block cell death in human macrophages. In keeping with such differences, the pore-forming toxin α-hemolysin mediated a substantial proportion of CFT073-triggered IL-1β secretion in mouse but not human macrophages. There was also a more substantial α-hemolysin-independent cell death response in human vs. mouse macrophages. Thus, in mouse macrophages, CFT073-triggered inflammasome responses are completely NLRP3-dependent, and largely α-hemolysin-dependent. In contrast, UPEC activates an NLRP3-independent cell death pathway and an α-hemolysin-independent IL-1β secretion pathway in human macrophages. This has important implications for understanding UTI in humans.

That’s Not For Our Kids: The strange death of philosophy and ethics in a low socioeconomic secondary school

This article reflects on the successes and failures of a new Philosophy and Ethics course in a low socioeconomic context in Perth, Western Australia, with the eventual demise of the subject in the school at the end of 2010. We frame this reflection within Deleuzian notions of geophilosophy to advocate for a Philosophy and Ethics that is informed by nomadic thought, as this offers a critical freedom for students to transform themselves and their society and suggests practical ways both of overcoming the prejudices which led to its demise and of student reluctance to engage in open discussion in class. We consider the demise of the course a ‘missed opportunity’ because it had so much potential to be transformative of student subjectivities in schools.

The death of lifelong employment in Japan?

Lifelong employment in Japan is more trope than literal fact. As a synecdoche,it encapsulates Japan's system of industrial relations. As a metonym, it epitomises the employee-oriented communitarian firm (Abe and Shimizutani,2007, p. 347). As a metaphor, it represents Japan's distinctive form of stakeholder capitalism (Dore, 1993). Yet none of these tropes holds as a truth. Lifelong employment does not signify the dominant form of employment in Japan. It does not privilege employees' interests over business concerns. And it does not constitute a benign, kinder form of capitalism compared with the market-based model.

The chromosome 16q region associated with ankylosing spondylitis includes the candidate gene tumour necrosis factor receptor type 1-associated death domain (TRADD)

Objective: To replicate and refine the reported association of ankylosing spondylitis (AS) with two nonsynonymous single nucleotide polymorphisms (nsSNPs) on chromosome 16q22.1. Methods: Firstly, 730 independent UK patients with AS were genotyped for rs9939768 and rs6979 and allele frequencies were compared with 2879 previously typed historic disease controls. Secondly, the two data sets were combined in meta-analyses. Finally, 5 tagging SNPs, located between rs9939768 and rs6979, were analysed in 1604 cases and 1020 controls. Results: The association of rs6979 with AS was replicated, p=0.03, OR=1.14 (95% CI 1.01 to 1.28), and a trend for association with rs9939768 detected, p=0.06, OR=1.25 (95% CI 0.99 to 1.57). Meta-analyses revealed association of both SNPs with AS, p=0.0008, OR=1.31 (95% CI 1.12 to 1.54) and p=0.0009, OR=1.15 (95% CI 1.06 to 1.23) for rs9939768 and rs6979, respectively. New associations with rs9033 and rs868213 (p=0.00002, OR=1.23 (95% CI 1.12 to 1.36) and p=0.00002 OR=1.45 (95% CI 1.22 to 1.72), respectively, were identified. Conclusions: The region on chromosome 16 that has been replicated in the present work is interesting as the highly plausible candidate gene, tumour necrosis factor receptor type 1 (TNFR1)-associated death domain (TRADD), is located between rs9033 and rs868213. It will require additional work to identify the primary genetic association(s) with AS.

Australian patients using a cardiac-diabetes web-based intervention program: Contributions to person-centered clinical practice

Rationale, aims and objectives: Patients with both cardiac disease and diabetes have poorer health outcomes than patients with only one chronic condition. While evidence indicates that internet based interventions may improve health outcomes for patients with a chronic disease, there is no literature on internet programs specific to cardiac patients with comorbid diabetes. Therefore this study aimed to develop a specific web-based program, then to explore patients’ perspectives on the usefulness of a new program. Methods: The interpretive approach using semi-structured interviews on a purposive sample of eligible patients with type 2 diabetes and a cardiac condition in a metropolitan hospital in Brisbane, Australia. Thematic analysis was undertaken to describe the perceived usefulness of a newly developed Heart2heart webpage. Results: Themes identified included confidence in hospital health professionals and reliance on doctors to manage conditions. Patients found the webpage useful for managing their conditions at home. Conclusions: The new Heart2heart webpage provided a positive and useful resource. Further research on to determine the potential influence of this resource on patients’ self-management behaviours is paramount. Implications for practice include using multimedia strategies for providing information to patients’ comorbidities of cardiac disease and type 2 diabetes, and further development on enhancement of such strategies

Fractional diffusion models of cardiac electrical propagation: Role of structural heterogeneity in dispersion of repolarization

Impulse propagation in biological tissues is known to be modulated by structural heterogeneity. In cardiac muscle, improved understanding on how this heterogeneity influences electrical spread is key to advancing our interpretation of dispersion of repolarization. We propose fractional diffusion models as a novel mathematical description of structurally heterogeneous excitable media, as a means of representing the modulation of the total electric field by the secondary electrical sources associated with tissue inhomogeneities. Our results, analysed against in vivo human recordings and experimental data of different animal species, indicate that structural heterogeneity underlies relevant characteristics of cardiac electrical propagation at tissue level. These include conduction effects on action potential (AP) morphology, the shortening of AP duration along the activation pathway and the progressive modulation by premature beats of spatial patterns of dispersion of repolarization. The proposed approach may also have important implications in other research fields involving excitable complex media.

Use of observed within-person variation of cardiac troponin in emergency department patients for determination of biological variation and percentage and absolute reference change values

BACKGROUND Many patients presenting to the emergency department (ED) for assessment of possible acute coronary syndrome (ACS) have low cardiac troponin concentrations that change very little on repeat blood draw. It is unclear if a lack of change in cardiac troponin concentration can be used to identify acutely presenting patients at low risk of ACS. METHODS We used the hs-cTnI assay from Abbott Diagnostics, which can detect cTnI in the blood of nearly all people. We identified a population of ED patients being assessed for ACS with repeat cTnI measurement who ultimately were proven to have no acute cardiac disease at the time of presentation. We used data from the repeat sampling to calculate total within-person CV (CV(T)) and, knowing the assay analytical CV (CV(A)), we could calculate within-person biological variation (CV(i)), reference change values (RCVs), and absolute RCV delta cTnI concentrations. RESULTS We had data sets on 283 patients. Men and women had similar CV(i) values of approximately 14%, which was similar at all concentrations <40 ng/L. The biological variation was not dependent on the time interval between sample collections (t = 1.5-17 h). The absolute delta critical reference change value was similar no matter what the initial cTnI concentration was. More than 90% of subjects had a critical reference change value <5 ng/L, and 97% had values of <10 ng/L. CONCLUSIONS With this hs-cTnI assay, delta cTnI seems to be a useful tool for rapidly identifying ED patients at low risk for possible ACS.

A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: A randomized clinical trial

IMPORTANCE Patients with chest pain represent a high health care burden, but it may be possible to identify a patient group with a low short-term risk of adverse cardiac events who are suitable for early discharge. OBJECTIVE To compare the effectiveness of a rapid diagnostic pathway with a standard-care diagnostic pathway for the assessment of patients with possible cardiac chest pain in a usual clinical practice setting. DESIGN, SETTING, AND PARTICIPANTS A single-center, randomized parallel-group trial with blinded outcome assessments was conducted in an academic general and tertiary hospital. Participants included adults with acute chest pain consistent with acute coronary syndrome for whom the attending physician planned further observation and troponin testing. Patient recruitment occurred from October 11, 2010, to July 4, 2012, with a 30-day follow-up. INTERVENTIONS An experimental pathway using an accelerated diagnostic protocol (Thrombolysis in Myocardial Infarction score, 0; electrocardiography; and 0- and 2-hour troponin tests) or a standard-care pathway (troponin test on arrival at hospital, prolonged observation, and a second troponin test 6-12 hours after onset of pain) serving as the control. MAIN OUTCOMES AND MEASURES Discharge from the hospital within 6 hours without a major adverse cardiac event occurring within 30 days. RESULTS Fifty-two of 270 patients in the experimental group were successfully discharged within 6 hours compared with 30 of 272 patients in the control group (19.3% vs 11.0%; odds ratio, 1.92; 95% CI, 1.18-3.13; P = .008). It required 20 hours to discharge the same proportion of patients from the control group as achieved in the experimental group within 6 hours. In the experimental group, 35 additional patients (12.9%) were classified as low risk but admitted to an inpatient ward for cardiac investigation. None of the 35 patients received a diagnosis of acute coronary syndrome after inpatient evaluation. CONCLUSIONS AND RELEVANCE Using the accelerated diagnostic protocol in the experimental pathway almost doubled the proportion of patients with chest pain discharged early. Clinicians could discharge approximately 1 of 5 patients with chest pain to outpatient follow-up monitoring in less than 6 hours. This diagnostic strategy could be easily replicated in other centers because no extra resources are required.

Atmospheric pressure gas plasma-induced colorectal cancer cell death is mediated by Nox2-ASK1 apoptosis pathways and oxidative stress is mitigated by Srx-Nrf2 anti-oxidant system

Atmospheric pressure gas plasma (AGP) generates reactive oxygen species (ROS) that induce apoptosis in cultured cancer cells. The majority of cancer cells develop a ROS-scavenging anti-oxidant system regulated by Nrf2, which confers resistance to ROS-mediated cancer cell death. Generation of ROS is involved in the AGP-induced cancer cell death of several colorectal cancer cells (Caco2, HCT116 and SW480) by activation of ASK1-mediated apoptosis signaling pathway without affecting control cells (human colonic sub-epithelial myofibroblasts; CO18, human fetal lung fibroblast; MRC5 and fetal human colon; FHC). However, the identity of an oxidase participating in AGP-induced cancer cell death is unknown. Here, we report that AGP up-regulates the expression of Nox2 (NADPH oxidase) to produce ROS. RNA interference designed to target Nox2 effectively inhibits the AGP-induced ROS production and cancer cell death. In some cases both colorectal cancer HT29 and control cells showed resistance to AGP treatment. Compared to AGP-sensitive Caco2 cells, HT29 cells show a higher basal level of the anti-oxidant system transcriptional regulator Nrf2 and its target protein sulfiredoxin (Srx) which are involved in cellular redox homeostasis. Silencing of both Nrf2 and Srx sensitized HT29 cells, leads to ROS overproduction and decreased cell viability. This indicates that in HT29 cells, Nrf2/Srx axis is a protective factor against AGP-induced oxidative stress. The inhibition of Nrf2/Srx signaling should be considered as a central target in drug-resistant colorectal cancer treatments.

Comparative genomic analysis of human Chlamydia pneumoniae isolates from respiratory, brain and cardiac tissues

Chlamydia pneumoniae is an obligate intracellular bacterium implicated in a wide range of human diseases including atherosclerosis and Alzheimer's disease. Efforts to understand the relationships between C. pneumoniae detected in these diseases have been hindered by the availability of sequence data for non-respiratory strains. In this study, we sequenced the whole genomes for C. pneumoniae isolates from atherosclerosis and Alzheimer's disease, and compared these to previously published C. pneumoniae genomes. Phylogenetic analyses of these new C. pneumoniae strains indicate two sub-groups within human C. pneumoniae, and suggest that both recombination and mutation events have driven the evolution of human C. pneumoniae. Further fine-detailed analyses of these new C. pneumoniae sequences show several genetically variable loci. This suggests that similar strains of C. pneumoniae are found in the brain, lungs and cardiovascular system and that only minor genetic differences may contribute to the adaptation of particular strains in human disease.

PW376 A pilot study of a post-discharge nurse-led, educational intervention on cardiac self-efficacy and anxiety in post-PCI patients

Introduction Hospitalisation for percutaneous coronary intervention (PCI) is often short, with limited nurse-teaching time and poor information absorption. Currently, patients are discharged home only to wait up to 4-8 weeks to commence a secondary prevention program and visit their cardiologist. This wait is an anxious time for patients and confidence or self-efficacy (SE) to self-manage may be low. Objectives To determine the effects of a nurse-led, educational intervention on participant SE and anxiety in the early post-discharge period. Methods A pilot study was undertaken as a randomised controlled clinical trial. Thirty-three participants were recruited, with n=13 randomised to the intervention group. A face-to-face, nurse-led, educational intervention was undertaken within the first 5-7 days post-discharge. Intervention group participants received standard post-discharge education, physical assessment, with a strong focus on the emotional impact of cardiovascular events and PCI. Early reiteration of post-discharge education was offered, along with health professional support with the aim to increase patients’ SE and to effectively manage their post-discharge health and well being, as well as anxieties. Self-efficacy to return to normal activities was measured to gauge participants’ abilities to manage post-PCI after attending the intervention using the cardiac self-efficacy (CSE) scale. State and trait anxiety was also measured using the State-Trait Anxiety Inventory (STAI) to determine if an increase in SE would influence participant anxiety. Results There were some increases in mean CSE scores in the intervention group participants over time. Areas of increase included return to normal social activities and confidence to change diet. Although reductions were observed in mean state and trait anxiety scores in both groups, an overall larger reduction in intervention group participants was observed over time. Conclusion It is essential that patients are given the education, support, and skills to self-manage in the early post-discharge period so that they have greater SE and are less anxious. This study provides some initial evidence that nurse-led support and education during this period, particularly the first week following PCI, is beneficial and could be trialled using alternate modes of communication to support remote and rural PCI patients and extend to other cardiovascular patients.