Metabolomic Profiling of In Vivo Plasma Responses to DioxinAssociated Dietary Contaminant Exposure in Rats: Implications for Identification of Sources of Animal and Human Exposure

Dioxin contamination of the food chain typically occurs when cocktails of combustion residues or polychlorinated biphenyl (PCB) containing oils become incorporated into animal feed. These highly toxic compounds are bioaccumulative with small amounts posing a major health risk. The ability to identify animal exposure to these compounds prior to their entry into the food chain may be an invaluable tool to safeguard public health. Dioxin-like compounds act by a common mode of action and this suggests that markers or patterns of response may facilitate identification of exposed animals. However, secondary co-contaminating compounds present in typical dioxin sources may affect responses to compounds. This study has investigated for the first time the potential of a metabolomics platform to distinguish between animals exposed to different sources of dioxin contamination through their diet. Sprague-Dawley rats were given feed containing dioxin-like toxins from hospital incinerator soot, a common PCB oil standard and pure 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (normalized at 0.1 µg/kg TEQ) and acquired plasma was subsequently biochemically profiled using ultra high performance liquid chromatography (UPLC) quadropole time-of-flight-mass spectrometry (QTof-MS). An OPLS-DA model was generated from acquired metabolite fingerprints and validated which allowed classification of plasma from individual animals into the four dietary exposure study groups with a level of accuracy of 97-100%. A set of 24 ions of importance to the prediction model, and which had levels significantly altered between feeding groups, were positively identified as deriving from eight identifiable metabolites including lysophosphatidylcholine (16:0) and tyrosine. This study demonstrates the enormous potential of metabolomic-based profiling to provide a powerful and reliable tool for the detection of dioxin exposure in food-producing animals.

Hospital antibiotic use and its relationship to age-adjusted comorbidity and alcohol-based hand rub consumption

SUMMARY The objective of this study was to evaluate the effect of age-adjusted comorbidity and alcohol-based hand rub on monthly hospital antibiotic usage, retrospectively. A multivariate autoregressive integrated moving average (ARIMA) model was built to relate the monthly use of all antibiotics grouped together with age-adjusted comorbidity and alcohol-based hand rub over a 5-year period (April 2005-March 2010). The results showed that monthly antibiotic use was positively related to the age-adjusted comorbidity index (concomitant effect, coefficient 1·103, P = 0·0002), and negatively related to the use of alcohol-based hand rub (2-month delay, coefficient -0·069, P = 0·0533). Alcohol-based hand rub is considered a modifiable factor and as such can be identified as a target for quality improvement programmes. Time-series analysis may provide a suitable methodology for identifying possible predictive variables that explain antibiotic use in healthcare settings. Future research should examine the relationship between infection control practices and antibiotic use, identify other infection control predictive factors for hospital antibiotic use, and evaluate the impact of enhancing different infection control practices on antibiotic use in a healthcare setting.

USING ‘NUTRITIONAL NARRATIVE’ AND FOCUS GROUPS TO UNDERSTAND HOW NUTRITIONAL CARE CAN BETTER PRIORITISED FOR OLDER PEOPLE IN HOSPITAL SETTINGS

Introduction: Poor nutritional status among older people is well documented with 40% of older people reported as malnourished on hospital admission. Poor nutrition contributes to increased infection, poorer patient outcomes and death and longer hospital stays. In this study, we assessed the ‘nutrition narrative’ from older hospital patients together with nutrition knowledge among nursing and medical staff and students.
Methods: The study used a convenience sample of older people (30, mean age 82 years) in two large geographically separate city hospitals. Patients mentally alert and consenting, gave a recorded ‘nutrition narrative’ to get a sense of how they felt their nutritional needs were being met in hospital. Main themes were identified by grounded analysis framework. Focus groups were recruited from medical/nursing teachers and students to assess their working knowledge of nutrition and the nutritional needs of the older patient group.
Results: Analysis of the ‘nutrition narrative’ suggested several themes (i) staff should listen to patients' needs/wishes in discussion with themselves and family members (ii) staff should continue to encourage and progress a positive eating experience (iii) staff should monitor food eaten/or not eaten and increase regular monitoring of weight. The focus groups with medical and nursing students suggested a limited knowledge about nutritional care of older people and little understanding about roles or cross-talk about nutrition across the multidisciplinary groups.
Conclusions: The ‘nutrition narrative’ themes suggested that the nutritional experience of older people in hospital can and must be improved. Nursing and medical staff providing medical and nursing care need better basic knowledge of nutrition and nutritional assessment, an improved understanding of the roles of the various multidisciplinary staff and of hospital catering pathways. Care professionals need to prioritise patient nutrition much more highly and recognise nutritional care as integral to patient healing and recovery

General Nurses’ Experiences of End-Of-Life Care in the Acute Hospital Setting

Approximately 90% of the UK population spend some time in hospital in their final year of life, and more than half of the population die in hospital. This review aims to explore the experiences of general nurses when providing end-of-life care to patients in the acute hospital setting. Nine studies were identified through a literature search, and each was then analysed and evaluated until themes emerged. Six themes were drawn from the literature: lack of education and knowledge, lack of time with patients, barriers arising in the culture of the health-care setting, communication barriers, symptom management, and nurses' personal issues. The themes cause concern about the quality of end-of-life care being provided in the acute care setting. The literature appears to be consistent in the view that terminally ill patients are best cared for in specialised care settings, such as palliative care units and hospices. However, increasing demands on health services will result in greater numbers of dying patients being admitted to the acute hospital setting. It is therefore paramount that general nurses' educational needs are met to ensure they develop clinical competence to provide high-quality holistic end-of-life care.

Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer

Failure to efficiently induce apoptosis contributes to cisplatin resistance in non-small-cell lung cancer (NSCLC). Although BCL-2-associated X protein (BAX) and BCL-2 antagonist killer (BAK) are critical regulators of the mitochondrial apoptosis pathway, their requirement has not been robustly established in relation to cisplatin. Here, we show that cisplatin can efficiently bypass mitochondrial apoptosis block caused by loss of BAX and BAK, via activation of the extrinsic death receptor pathway in some model cell lines. Apoptosis resistance following cisplatin can only be observed when both extrinsic and intrinsic pathways are blocked, consistent with redundancy between mitochondrial and death receptor pathways in cisplatin-induced apoptosis. In H460 NSCLC cells, caspase-8 cleavage was shown to be induced by cisplatin and is dependent on death receptor 4, death receptor 5, Fas-associated protein with death domain, acid sphingomyelinase and ceramide synthesis. In contrast, cisplatin-resistant cells fail to activate caspase-8 via this pathway despite conserving sensitivity to death ligand-driven activation. Accordingly, caspase-8 activation block acquired during cisplatin resistance, can be bypassed by death receptor agonism. © 2012 Macmillan Publishers Limited

Testing a model for developing, implementing and evaluating a strategy to improve the quality of nursing and midwifery care in an acute hospital trust.

Abstract:
Background: Health care organisations
worldwide are faced with the need to develop
and implement strategic organisational plans
to meet the challenges of modern health care.
There is a need for models for developing, implementing and evaluating strategic plans that engage practitioners, and make a measurable difference to the patients that they serve. These presentations describe the development, implementation and evaluation of such a model by a team of senior nurses and practice developers, to underpin a strategy for nursing and midwifery in an acute hospital trust. Developing a Strategy The PARIHS (Promoting Action on Research Implementation in Health Services) conceptual framework (Kitson et al, 1998) proposes that successful implementation of change in practice is a function of the interplay of three core elements: the level of evidence supporting the proposed change; the context or environment in which the change takes place, and the way in which change is facilitated. We chose to draw on this framework to develop our strategy and implementation plan (O’Halloran, Martin and Connolly, 2005). At the centre of the plan are ward managers. These professionals provide leadership for the majority of staff in the trust and so were seen to be a key group in the implementation process.

Description and predictors of hospital costs of oesophageal cancer during the first year following diagnosis in Northern Ireland

The cost-effectiveness of novel interventions in the treatment of cancer is well researched; however, relatively little attention is paid to the cost of many aspects of routine care. Oesophageal cancer is the ninth most common cancer in the UK and sixth most common cause of cancer death. It usually presents late and has a poor prognosis. The hospital costs incurred by oesophageal cancer patients diagnosed in Northern Ireland in 2005 (n = 198) were determined by review of medical records. The average cost of hospital care per patient in the 12 months from presentation was £7847. Variations in total hospital costs by age at diagnosis, gender, cancer stage, histological type, mortality at 1 year, co-morbidity count and socio-economic status were analysed using multiple regression analyses. Higher costs were associated with earlier stages of cancer and cancer stage remained a significant predictor of costs after controlling for cancer type, patient age and mortality at 1 year. Thus, although early detection of cancer usually improves survival, this would mean increased costs in the first year. Deprivation achieved borderline significance with those from more deprived areas having lower resource consumption relative to the more affluent. © 2013 John Wiley & Sons Ltd.

Newly Acquired Fear of Falling Leads to Altered Eye Movement Patterns and Reduced Stepping Safety: A Case Study

This opportune case study describes visual and stepping behaviours of an 87 year old female (P8), both prior to, and following two falls. Before falling, when asked to walk along a path containing two stepping guides positioned before and after an obstacle, P8 generally visually fixated the first stepping guide until after foot contact inside it. However, after falling P8 consistently looked away from the stepping guide before completing the step into it in order to fixate the upcoming obstacle in her path. The timing of gaze redirection away from the target (in relation to foot contact inside it) correlated with absolute stepping error. No differences in eyesight, cognitive function, or balance were found between pre- and post-fall recordings. However, P8 did report large increases in fall-related anxiety and reduced balance confidence, supporting previously suggested links between anxiety/increased fear or falling and maladaptive visual/stepping behaviours. The results represent a novel insight into how psychological and related behavioural factors can change in older adults following a fall, and provide a possible partial rationalisation for why recent fallers are more likely to fall again in the following 12 months. These findings highlight novel possibilities for falls prevention and rehabilitation.

Ventilator-associated pneumonia is characterized by excessive release of neutrophil proteases in the lung

Ventilator-associated pneumonia (VAP) is characterized by neutrophils infiltrating the alveolar space. VAP is associated with high mortality, and accurate diagnosis remains difficult. We hypothesized that proteolytic enzymes from neutrophils would be significantly increased and locally produced inhibitors of human neutrophil elastase (HNE) would be decreased in BAL fluid (BALF) from patients with confirmed VAP. We postulated that in suspected VAP, neutrophil proteases in BALF may help identify "true" VAP.

Impact of community based, specialist palliative care teams on hospitalisations and emergency department visits late in life and hospital deaths: a pooled analysis

Objective: To determine the pooled effect of exposure to one of 11 specialist palliative care teams providing services in patients’ homes.Design: Pooled analysis of a retrospective cohort study.Setting: Ontario, Canada.Participants: 3109 patients who received care from specialist palliative care teams in 2009-11 (exposed) matched by propensity score to 3109 patients who received usual care (unexposed).Intervention: The palliative care teams studied served different geographies and varied in team composition and size but had the same core team members and role: a core group of palliative care physicians, nurses, and family physicians who provide integrated palliative care to patients in their homes. The teams’ role was to manage symptoms, provide education and care, coordinate services, and be available without interruption regardless of time or day.Main outcome measures: Patients (a) being in hospital in the last two weeks of life; (b) having an emergency department visit in the last two weeks of life; or (c) dying in hospital.Results: In both exposed and unexposed groups, about 80% had cancer and 78% received end of life homecare services for the same average duration. Across all palliative care teams, 970 (31.2%) of the exposed group were in hospital and 896 (28.9%) had an emergency department visit in the last two weeks of life respectively, compared with 1219 (39.3%) and 1070 (34.5%) of the unexposed group (P<0.001). The pooled relative risks of being in hospital and having an emergency department visit in late life comparing exposed versus unexposed were 0.68 (95% confidence interval 0.61 to 0.76) and 0.77 (0.69 to 0.86) respectively. Fewer exposed than unexposed patients died in hospital (503 (16.2%) v 887 (28.6%), P<0.001), and the pooled relative risk of dying in hospital was 0.46 (0.40 to 0.52).Conclusions: Community based specialist palliative care teams, despite variation in team composition and geographies, were effective at reducing acute care use and hospital deaths at the end of life.