Ultrafiltration rate is a poor indicator of haemodialysis nursing quality. Commentary on Lindberg and Ludvigsen (2012)

In their paper Lindberg and Ludvigsen (2012) have correctly identified the lack of evidence-based nurse-sensitive indicators measuring the quality of haemodialysis nursing care. The authors suggest that the intradialytic ultrafiltration rate (UFR) (total fluid removed divided by the total time in a single dialysis treatment, measured in litres per hour) may be one such indicator. Importantly it is best practice to minimise high UFRs as they are associated with higher risk of cardiovascular events and vascular access complications (Curatola et al., 2011). However, this does not justify UFR to qualify as a nurse-sensitive indicator of quality in the haemodialysis context. The aim of this response is to voice our concerns over the proposal to use haemodialysis treatment UFR as a haemodialysis nurse-sensitive quality indicator...

Job satisfaction in haemodialysis nurses : results from a two country study

• Australian nurses report lower levels of job satisfaction than the broader working population and perceive they have limited influence over important workplace decisions. • Higher levels of nurse job satisfaction is positively linked to improved quality of care, patient outcomes and staff retention. • Identifying factors that contribute to job satisfaction can improve retention of highly skilled and specialised haemodialysis nurses. • Contributors to job satisfaction and current levels of job satisfaction are poorly understood in the Australia and New Zealand context.

Development and testing of an iPad application for teaching self-management to heart failure patients. (Nursing/Allied Health Professional Investigator Award)- Abstract

Purpose: Heart failure (HF) is the leading cause of hospitalization and significant burden to the health care system in Australia. To reduce hospitalizations, multidisciplinary approaches and enhance self-management programs have been strongly advocated for HF patients globally. HF patients who can effectively manage their symptoms and adhere to complex medicine regimes will experience fewer hospitalizations. Research indicates that information technologies (IT) have a significant role in providing support to promote patients' self-management skills. The iPad utilizes user-friendly interfaces and to date an application for HF patient education has not been developed. This project aimed to develop the HF iPad teaching application in the way that would be engaging, interactive and simple to follow and usable for patients' carers and health care workers within both the hospital and community setting. Methods: The design for the development and evaluation of the application consisted of two action research cycles. Each cycle included 3 phases of testing and feedback from three groups comprising IT team, HF experts and patients. All patient education materials of the application were derived from national and international evidence based practice guidelines and patient self-care recommendations. Results: The iPad application has animated anatomy and physiology that simply and clearly teaches the concepts of the normal heart and the heart in failure. Patient Avatars throughout the application can be changed to reflect the sex and culture of the patient. There is voice-over presenting a script developed by the heart failure expert panel. Additional engagement processes included points of interaction throughout the application with touch screen responses and the ability of the patient to enter their weight and this data is secured and transferred to the clinic nurse and/or research data set. The application has been used independently, for instance, at home or using headphones in a clinic waiting room or most commonly to aid a nurse-led HF consultation. Conclusion: This project utilized iPad as an educational tool to standardize HF education from nurses who are not always heart failure specialists. Furthermore, study is currently ongoing to evaluate of the effectiveness of this tool on patient outcomes and to develop several specifically designed cultural adaptations [Hispanic (USA), Aboriginal (Australia), and Maori (New Zealand)].

The Development of Competency Standards for Specialist Critical Care Nurses

In defining the contemporary role of the specialist nurse it is necessary to challenge the concept of nursing as merely a combination of skills and knowledge. Nursing must be demonstrated and defined in the context of client care and include the broader notions of professional development and competence. This qualitative study sought to identify the competency standards for nurse specialists in critical care and to articulate the differences between entry-to-practice standards and the advanced practice of specialist nurses. Over 800 hours of specialist critical care nursing practice were observed and grouped into 'domains' or major themes of specialist practice using a constant comparison qualitative technique. These domains were further refined to describe attributes of the registered nurses which resulted in effective and/or superior performance (competency standards) and to provide examples of performance (performance criteria) which met the defined standard. Constant comparison of the emerging domains, competency standards and performance criteria to observations of specialist critical care practice, ensured the results provided a true reflection of the specialist nursing role. Data analysis resulted in 20 competency standards grouped into six domains: professional practice, reflective practice, enabling, clinical problem solving, teamwork, and leadership. Each of these domains is comprised of between two and seven competency standards. Each standard is further divided into component parts or 'elements' and the elements are illustrated with performance criteria. The competency standards are currently being used in several Australian critical care educational programmes and are the foundation for an emerging critical care credentialling process. They have been viewed with interest by a variety of non-critical care specialty groups and may form a common precursor from which further specialist nursing practice assessment will evolve.

Krüppel-associated box (KRAB)-associated co-repressor (KAP-1) Ser-473 phosphorylation regulates heterochromatin protein 1 (HP1- ) mobilization and DNA repair in heterochromatin

The DNA damage response encompasses a complex series of signaling pathways that function to regulate and facilitate the repair of damaged DNA. Recent studies have shown that the repair of transcriptionally inactive chromatin, named heterochromatin, is dependent upon the phosphorylation of the co-repressor, Krüppel-associated box (KRAB) domain-associated protein (KAP-1), by the ataxia telangiectasia-mutated (ATM) kinase. Co-repressors, such as KAP-1, function to regulate the rigid structure of heterochromatin by recruiting histone-modifying enzymes, such HDAC1/2, SETDB1, and nucleosome-remodeling complexes such as CHD3. Here, we have characterized a phosphorylation site in the HP1-binding domain of KAP-1, Ser-473, which is phosphorylated by the cell cycle checkpoint kinase Chk2. Expression of a nonphosphorylatable S473A mutant conferred cellular sensitivity to DNA-damaging agents and led to defective repair of DNA double-strand breaks in heterochromatin. In addition, cells expressing S473A also displayed defective mobilization of the HP1-β chromodomain protein. The DNA repair defect observed in cells expressing S473A was alleviated by depletion of HP1-β, suggesting that phosphorylation of KAP-1 on Ser-473 promotes the mobilization of HP1-β from heterochromatin and subsequent DNA repair. These results suggest a novel mechanism of KAP-1-mediated chromatin restructuring via Chk2-regulated HP1-β exchange from heterochromatin, promoting DNA repair.

BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma

The rapeutic options for malignant pleural mesothelioma (MPM) are limited despite the increasing incidence globally. The vinca alkaloid vinorelbine exhibits clinical activity; however, to date, treatment optimization has not been achieved using biomarkers. BRCA1 regulates sensitivity to microtubule poisons; however, its role in regulating vinorelbine-induced apoptosis in mesothelioma is unknown. Here we demonstrate that BRCA1 plays an essential role in mediating vinorelbine-induced apoptosis, as evidenced by (1) the strong correlation between vinorelbine sensitivity and BRCA1 expression level; (2) induction of resistance to vinorelbine by BRCA1 using siRNA oligonucleotides; (3) dramatic down-regulation of BRCA1 following selection for vinorelbine resistance; and (4) the re-activation of vinorelbine-induced apoptosis following re-expression of BRCA1 in resistant cells. To determine whether loss of BRCA1 expression in mesothelioma was potentially relevant in vivo, BRCA1 immunohistochemistry was subsequently performed on 144 primary mesothelioma specimens. Loss of BRCA1 protein expression was identified in 38.9% of samples. Together, these data suggest that BRCA1 plays a critical role in mediating apoptosis by vinorelbine in mesothelioma, warranting its clinical evaluation as a predictive biomarker. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

INT6/EIF3E interacts with ATM and is required for proper execution of the DNA damage response in human cells

Altered expression of the INT6 gene, encoding the e subunit of the translational initiation factor eIF3, occurs in human breast cancers, but how INT6 relates to carcinogenesis remains unestablished. Here, we show that INT6 is involved in the DNA damage response. INT6 was required for cell survival following γ-irradiation and G(2)-M checkpoint control. RNA interference-mediated silencing of INT6 reduced phosphorylation of the checkpoint kinases CHK1 and CHK2 after DNA damage. In addition, INT6 silencing prevented sustained accumulation of ataxia telangiectasia mutated (ATM) at DNA damage sites in cells treated with γ-radiation or the radiomimetic drug neocarzinostatin. Mechanistically, this result could be explained by interaction of INT6 with ATM, which together with INT6 was recruited to the sites of DNA damage. Finally, INT6 silencing also reduced ubiquitylation events that promote retention of repair proteins at DNA lesions. Accordingly, accumulation of the repair factor BRCA1 was defective in the absence of INT6. Our findings reveal unexpected and striking connections of INT6 with ATM and BRCA1 and suggest that the protective action of INT6 in the onset of breast cancers relies on its involvement in the DNA damage response.

Contribution of DEAF1 structural domains to the interaction with the breast cancer oncogene LMO4

The proteins LMO4 and DEAF1 contribute to the proliferation of mammary epithelial cells. During breast cancer LMO4 is upregulated, affecting its interaction with other protein partners. This may set cells on a path to tumour formation. LMO4 and DEAF1 interact, but it is unknown how they cooperate to regulate cell proliferation. In this study, we identify a specific LMO4-binding domain in DEAF1. This domain contains an unstructured region that directly contacts LMO4, and a coiled coil that contains the DEAF1 nuclear export signal (NES). The coiled coil region can form tetramers and has the typical properties of a coiled coil domain. Using a simple cell-based assay, we show that LMO4 modulates the activity of the DEAF NES, causing nuclear accumulation of a construct containing the LMO4-interaction region of DEAF1.

Circulating tumour cells, their role in metastasis and their clinical utility in lung cancer

Circulating tumour cells (CTCs) have attracted much recent interest in cancer research as a potential biomarker and as a means of studying the process of metastasis. It has long been understood that metastasis is a hallmark of malignancy, and conceptual theories on the basis of metastasis from the nineteenth century foretold the existence of a tumour "seed" which is capable of establishing discrete tumours in the "soil" of distant organs. This prescient "seed and soil" hypothesis accurately predicted the existence of CTCs; microscopic tumour fragments in the blood, at least some of which are capable of forming metastases. However, it is only in recent years that reliable, reproducible methods of CTC detection and analysis have been developed. To date, the majority of studies have employed the CellSearch™ system (Veridex LLC), which is an immunomagnetic purification method. Other promising techniques include microfluidic filters, isolation of tumour cells by size using microporous polycarbonate filters and flow cytometry-based approaches. While many challenges still exist, the detection of CTCs in blood is becoming increasingly feasible, giving rise to some tantalizing questions about the use of CTCs as a potential biomarker. CTC enumeration has been used to guide prognosis in patients with metastatic disease, and to act as a surrogate marker for disease response during therapy. Other possible uses for CTC detection include prognostication in early stage patients, identifying patients requiring adjuvant therapy, or in surveillance, for the detection of relapsing disease. Another exciting possible use for CTC detection assays is the molecular and genetic characterization of CTCs to act as a "liquid biopsy" representative of the primary tumour. Indeed it has already been demonstrated that it is possible to detect HER2, KRAS and EGFR mutation status in breast, colon and lung cancer CTCs respectively. In the course of this review, we shall discuss the biology of CTCs and their role in metastagenesis, the most commonly used techniques for their detection and the evidence to date of their clinical utility, with particular reference to lung cancer.

Generation and characterisation of Cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature

Introduction: Inherent and acquired cisplatin resistance reduces the effectiveness of this agent in the management of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms underlying this process may result in the development of novel agents to enhance the sensitivity of cisplatin. Methods: An isogenic model of cisplatin resistance was generated in a panel of NSCLC cell lines (A549, SKMES-1, MOR, H460). Over a period of twelve months, cisplatin resistant (CisR) cell lines were derived from original, age-matched parent cells (PT) and subsequently characterized. Proliferation (MTT) and clonogenic survival assays (crystal violet) were carried out between PT and CisR cells. Cellular response to cisplatin-induced apoptosis and cell cycle distribution were examined by FACS analysis. A panel of cancer stem cell and pluripotent markers was examined in addition to the EMT proteins, c-Met and β-catenin. Cisplatin-DNA adduct formation, DNA damage (γH2AX) and cellular platinum uptake (ICP-MS) was also assessed. Results: Characterisation studies demonstrated a decreased proliferative capacity of lung tumour cells in response to cisplatin, increased resistance to cisplatin-induced cell death, accumulation of resistant cells in the G0/G1 phase of the cell cycle and enhanced clonogenic survival ability. Moreover, resistant cells displayed a putative stem-like signature with increased expression of CD133+/CD44+cells and increased ALDH activity relative to their corresponding parental cells. The stem cell markers, Nanog, Oct-4 and SOX-2, were significantly upregulated as were the EMT markers, c-Met and β-catenin. While resistant sublines demonstrated decreased uptake of cisplatin in response to treatment, reduced cisplatin-GpG DNA adduct formation and significantly decreased γH2AX foci were observed compared to parental cell lines. Conclusion: Our results identified cisplatin resistant subpopulations of NSCLC cells with a putative stem-like signature, providing a further understanding of the cellular events associated with the cisplatin resistance phenotype in lung cancer. © 2013 Barr et al.

The cancer stem-cell hypothesis : its emerging role in lung cancer biology and its relevance for future therapy

The cancer stem-cell (CSC) hypothesis suggests that there is a small subset of cancer cells that are responsible for tumor initiation and growth, possessing properties such as indefinite self-renewal, slow replication, intrinsic resistance to chemotherapy and radiotherapy, and an ability to give rise to differentiated progeny. Through the use of xenotransplantation assays, putative CSCs have been identified in many cancers, often identified by markers usually expressed in normal stem cells. This is also the case in lung cancer, and the accumulated data on side population cells, CD133, CD166, CD44 and ALDH1 are beginning to clarify the true phenotype of the lung cancer stem cell. Furthermore, it is now clear that many of the pathways of normal stem cells, which guide cellular proliferation, differentiation, and apoptosis are also prominent in CSCs; the Hedgehog (Hh), Notch, and Wnt signaling pathways being notable examples. The CSC hypothesis suggests that there is a small reservoir of cells within the tumor, which are resistant to many standard therapies, and can give rise to new tumors in the form of metastases or relapses after apparent tumor regression. Therapeutic interventions that target CSC pathways are still in their infancy and clinical data of their efficacy remain limited. However Smoothened inhibitors, gamma-secretase inhibitors, anti-DLL4 antagonists, Wnt antagonists, and CBP/β-catenin inhibitors have all shown promising anticancer effects in early studies. The evidence to support the emerging picture of a lung cancer CSC phenotype and the development of novel therapeutic strategies to target CSCs are described in this review.

School based youth health nurses and a true health promotion approach : the Ottawa what?

Aim: The purpose of this research is to examine School Based Youth Health Nurses experience of a true health promotion approach. Background: The School Based Youth Health Nurse Program is a state-wide school nursing initiative in Queensland, Australia. The program employs more than 120 fulltime and fractional school nurses who provide health services in state high schools. The role incorporates two primary components: individual health consultations and health promotion strategies. Design/Methods: This study is a retrospective inquiry generated from a larger qualitative research project about the experience of school based youth health nursing. The original methodology was phenomenography. In-depth interviews were conducted with sixteen school nurses recruited through purposeful and snowball sampling. This study accesses a specific set of raw data about School Based Youth Health Nurses experience of a true health promotion approach. The Ottawa Charter for Health Promotion (1986) is used as a framework for deductive analysis. Results: The findings indicate school nurses have neither an adverse or affirmative conceptual experience of a true health promotion approach and an adverse operational experience of a true health promotion approach based on the action areas of the Ottawa Charter. Conclusions: The findings of this research are important because they challenge the notion that school nurses are the most appropriate health professionals to undertake a true health promotion approach. If school nurses are the most appropriate health professionals to do a true health promotion approach, there are implications for recruitment and training and qualifications. If school nurses are not, who are the most appropriate health professionals to do school health promotion? Implications for Practice: These findings can be applied to other models of school nursing in Australia which emphasises a true health promotion approach because they relate specifically to school nurses’ experience of a true health promotion approach.

Delineating the practice profile of advanced practice nursing : a cross-sectional survey using the modified strong model of advanced practice

AIMS: To test a model that delineates advanced practice nursing from the practice profile of other nursing roles and titles. BACKGROUND: There is extensive literature on advanced practice reporting the importance of this level of nursing to contemporary health service and patient outcomes. Literature also reports confusion and ambiguity associated with advanced practice nursing. Several countries have regulation and delineation for the nurse practitioner, but there is less clarity in definition and service focus of other advanced practice nursing roles. DESIGN: A statewide survey. METHODS: Using the modified Strong Model of Advanced Practice Role Delineation tool, a survey was conducted in 2009 with a random sample of registered nurses/midwives from government facilities in Queensland, Australia. Analysis of variance compared total and subscale scores across groups according to grade. Linear, stepwise multiple regression analysis examined factors influencing advanced practice nursing activities across all domains. RESULTS: There were important differences according to grade in mean scores for total activities in all domains of advanced practice nursing. Nurses working in advanced practice roles (excluding nurse practitioners) performed more activities across most advanced practice domains. Regression analysis indicated that working in clinical advanced practice nursing roles with higher levels of education were strong predictors of advanced practice activities overall. CONCLUSION: Essential and appropriate use of advanced practice nurses requires clarity in defining roles and practice levels. This research delineated nursing work according to grade and level of practice, further validating the tool for the Queensland context and providing operational information for assigning innovative nursing service.

Using the Donabedian framework to examine the quality and safety of nursing service innovation

Aims and objectives To evaluate the safety and quality of nurse practitioner service using the audit framework of Structure,Process and Outcome. Background Health service and workforce reform are on the agenda of governments and other service providers seeking to contain healthcare costs whilst providing safe and effective health care to communities. The nurse practitioner service is one health workforce innovation that has been adopted globally to improve timely access to clinical care, but there is scant literature reporting evaluation of the quality of this service innovation. Design. A mixed-methods design within the Donabedian evaluation framework was used. Methods The Donabedian framework was used to evaluate the Structure, Process and Outcome of nurse practitioner service. A range of data collection approaches was used, including stakeholder survey (n=36), in-depth interviews (11 patients and 13 nurse practitioners) and health records data on service processes. Results The study identified that adequate and detailed preparation of Structure and Process is essential for the successful implementation of a service innovation. The multidisciplinary team was accepting of the addition of nurse practitioner service, and nurse practitioner clinical care was shown to be effective, satisfactory and safe from the perspective of the clinician stakeholders and patients. Conclusions This study demonstrated that the Donabedian framework of Structure, Process and Outcome evaluation is a valuable and validated approach to examine the safety and quality of a service innovation. Furthermore, in this study, specific Structure elements were shown to influence the quality of service processes further validating the framework and the interdependence of the Structure, Process and Outcome components. Relevance to clinical practice Understanding the structure and process requirements for establishing nursing service innovation lays the foundation for safe, effective and patient-centred clinical care.