New insights into appetite, inflammation and the use of fish oil in hemodialysis patients

Protein-energy wasting (PEW) is commonly seen in patients with chronic kidney disease (CKD). The condition is characterised by chronic, systemic low-grade inflammation which affects nutritional status by a variety of mechanisms including reducing appetite and food intake and increasing muscle catabolism. PEW is linked with co-morbidities such as cardiovascular disease, and is associated with lower quality of life, increased hospitalisations and a 6-fold increase in risk of death1. Significant gender differences have been found in the severity and effects of several markers of PEW. There have been limited studies testing the ability of anti-inflammatory agents or nutritional interventions to reduce the effects of PEW in dialysis patients. This thesis makes a significant contribution to the understanding of PEW in dialysis patients. It advances understanding of measurement techniques for two of the key components, appetite and inflammation, and explores the effect of fish oil, an anti-inflammatory agent, on markers of PEW in dialysis patients. The first part of the thesis consists of two methodological studies conducted using baseline data. The first study aims to validate retrospective ratings of hunger, desire to eat and fullness on visual analog scales (VAS) (paper and pen and electronic) as a new method of measuring appetite in dialysis patients. The second methodological study aims to assess the ability of a variety of methods available in routine practice to detect the presence of inflammation. The second part of the thesis aims to explore the effect of 12 weeks supplementation with 2g per day of Eicosapentaenoic Acid (EPA), a longchain fatty acid found in fish oil, on markers of PEW. A combination of biomarkers and psychomarkers of appetite and inflammation are the main outcomes being explored, with nutritional status, dietary intake and quality of life included as secondary outcomes. A lead in phase of 3 months prior to baseline was used so that each person acts as their own historical control. The study also examines whether there are gender differences in response to the treatment. Being an exploratory study, an important part of the work is to test the feasibility of the intervention, thus the level of adherence and factors associated with adherence are also presented. The studies were conducted at the hemodialysis unit of the Wesley Hospital. Participants met the following criteria: adult, stage 5 CKD on hemodialysis for at least 3 months, not expected to receive a transplant or switch to another dialysis modality during the study, absence of intellectual impairment or mental illness impairing ability to follow instructions or complete the intervention. A range of intermediate, clinical and patient-centred outcome measures were collected at baseline and 12 weeks. Inflammation was measured using five biomarkers: c-reactive protein (CRP), interleukin-6 (IL6), intercellular adhesion molecule (sICAM-1), vascular cell adhesion molecule (sVCAM-1) and white cell count (WCC). Subjective appetite was measured using the first question from the Appetite and Dietary Assessment (ADAT) tool and VAS for measurements of hunger, desire to eat and fullness. A novel feature of the study was the assessment of the appetite peptides leptin, ghrelin and peptide YY as biomarkers of appetite. Nutritional status/inflammation was assessed using the Malnutrition-Inflammation Score (MIS) and the Patient-Generated Subjective Global Assessment (PG-SGA). Dietary intake was measured using 3-day records. Quality of life was measured using the Kidney Disease Quality of Life Short Form version 1.3 (KDQOL-SF™ v1.3 © RAND University), which combines the Short-Form 36 (SF36) with a kidney-disease specific module2. A smaller range of these variables was available for analysis during the control phase (CRP, ADAT, dietary intake and nutritional status). Statistical analysis was carried out using SPSS version 14 (SPSS Inc, Chicago IL, USA). Analysis of the first part of the thesis involved descriptive and bivariate statistics, as well as Bland-Altman plots to assess agreement between methods, and sensitivity analysis/ROC curves to test the ability of methods to predict the presence of inflammation. The unadjusted (paired ttests) and adjusted (linear mixed model) change over time is presented for the main outcome variables of inflammation and appetite. Results are shown for the whole group followed by analyses according to gender and adherence to treatment. Due to the exploratory nature of the study, trends and clinical significance were considered as important as statistical significance. Twenty-eight patients (mean age 61±17y, 50% male, dialysis vintage 19.5 (4- 101) months) underwent baseline assessment. Seven out of 28 patients (25%) reported sub-optimal appetite (self-reported as fair, poor or very poor) despite all being well nourished (100% SGA A). Using the VAS, ratings of hunger, but not desire to eat or fullness, were significantly (p<0.05) associated with a range of relevant clinical variables including age (r=-0.376), comorbidities (r=-0.380) nutritional status (PG-SGA score, r=-0.451), inflammatory markers (CRP r=-0.383; sICAM-1 r=-0.387) and seven domains of quality of life. Patients expressed a preference for the paper and pen method of administering VAS. None of the tools (appetite, MIS, PG-SGA, albumin or iron) showed an acceptable ability to detect patients who are inflamed. It is recommended that CRP should be tested more frequently as a matter of course rather than seeking alternative methods of measuring inflammation. 27 patients completed the 12 week intervention. 20 patients were considered adherent based on changes in % plasma EPA, which rose from 1.3 (0.94)% to 5.2 (1.1)%, p<0.001, in this group. The major barriers to adherence were forgetting to take the tablets as well as their size. At 12 weeks, inflammatory markers remained steady apart from the white cell count which decreased (7.6(2.5) vs 7.0(2.2) x109/L, p=0.058) and sVCAM-1 which increased (1685(654) vs 2249(925) ng/mL, p=0.001). Subjective appetite using VAS increased (51mm to 57mm, +12%) and there was a trend towards reduction in peptide YY (660(31) vs 600(30) pg/mL, p=0.078). There were some gender differences apparent, with the following adjusted change between baseline and week 12: CRP (males -3% vs females +17%, p=0.19), IL6 (males +17% vs females +48%, p=0.77), sICAM-1 (males -5% vs females +11%, p=0.07), sVCAM-1 (males +54% vs females +19%, p=0.08) and hunger ratings (males 20% vs females -5%, p=0.18). On balance, males experienced a maintainence or reduction in three inflammatory markers and an improvement in hunger ratings, and therefore appeared to have responded better to the intervention. Compared to those who didn’t adhere, adherent patients maintained weight (mean(SE) change: +0.5(1.6) vs - 0.8(1.2) kg, p=0.052) and fat-free mass (-0.1 (1.6) vs -1.8 (1.8) kg, p=0.045). There was no difference in change between the intervention and control phase for CRP, appetite, nutritional status or dietary intake. The thesis makes a significant contribution to the evidence base for understanding of PEW in dialysis patients. It has advanced knowledge of methods of assessing inflammation and appetite. Retrospective ratings of hunger on a VAS appear to be a valid method of assessing appetite although samples which include patients with very poor appetite are required to confirm this. Supplementation with fish oil appeared to improve subjective appetite and dampen the inflammatory response. The effectiveness of the intervention is influenced by gender and adherence. Males appear to be more responsive to the primary outcome variables than females, and the quality of response is improved with better adherence. These results provide evidence to support future interventions aimed at reducing the effects of PEW in dialysis patients.

A review of the economic consequences of a policy of universal leucodepletion as compared to existing practices

Leucodepletion, the removal of leucocytes from blood products improves the safety of blood transfusion by reducing adverse events associated with the incidental non-therapeutic transfusion of leucocytes. Leucodepletion has been shown to have clinical benefit for immuno-suppressed patients who require transfusion. The selective leucodepletion of blood products by bed side filtration for these patients has been widely practiced. This study investigated the economic consequences in Queensland of moving from a policy of selective leucodepletion to one of universal leucodepletion, that is providing all transfused patients with blood products leucodepleted during the manufacturing process. Using an analytic decision model a cost-effectiveness analysis was conducted. An ICER of $16.3M per life year gained was derived. Sensitivity analysis found this result to be robust to uncertainty in the parameters used in the model. This result argues against moving to a policy of universal leucodepletion. However during the course of the study the policy decision for universal leucodepletion was made and implemented in Queensland in October 2008. This study has concluded that cost-effectiveness is not an influential factor in policy decisions regarding quality and safety initiatives in the Australian blood sector.

POOR ICARUS CHARMIAN : Review of The Life and Myth of Charmian Clift by Nadia Wheatley (2001) online

Online Review

Blogs, wikis and podcasts : collaborative knowledge building tools in a design and technology course

Design and Technology has become an important part of the school curriculum. In Queensland, Australia, Technology (which encompasses Design) is one of the Key Learning Areas (KLAs) for students in the first ten years of schooling. This KLA adopts a student-centred, hands-on constructivist approach to teaching and learning. The ability to conceptualise and implement appropriate learning experiences, however, has been a challenge for some early career teachers. This paper describes how Design and Technology is being taught to pre-service primary teachers at an Australian University through their involvement in a range of authentic problem-solving activities supported by social learning tools such as wikis and blogs. An interview with a sample from this group (N=5) provides an insight into how these social software tools enhanced their knowledge and learning. This paper will describe how these social learning tools impact on the agency of learning.

Romance and Reconciliation : The secret life of indigenous sexuality on Australian television drama

This article examines the representation of Indigenous sexuality on Australian television drama since the 1970s, suggesting the political importance of such representations. In 1976 Justine Saunders became the first regular Indigenous character on an Australian television drama series, as the hairdresser Rhonda Jackson in Number 96. She was presented as sexually attractive, but this was expressed through a rape scene after a party. Twenty five years later, Deborah Mailman starred in The Secret Life of Us, as Kelly, who is also presented as sexually attractive. But her character can be seen in many romantic relationships. The article explores changing representations that moved us from Number 96 to The Secret Life of Us, via The Flying Doctors and Heartland. It suggests that in representations of intimate and loving relationships on screen it has only recently become possible to see hopeful models for interaction between Indigenous and non-Indigenous Australians.

Extending life-cycle costing (LCC) analysis for sustainability considerations in road infrastructure projects

Sustainable development is about making societal investments. These investments should be in synchronization with the natural environment, trends of social development, as well as organisational and local economies over a long time span. Traditionally in the eyes of clients, project development will need to produce the required profit margins, with some degrees of consideration for other impacts. This is being changed as all citizens of our society are becoming more aware of concepts and challenges such as the climate change, greenhouse footprints, and social dimensions of sustainability, and will in turn demand answers to these issues in built facilities. A large number of R&D projects have focused on the technical advancement and environmental assessment of products and built facilities. It is equally important address the cost/benefit issue, as developers in the world would not want to loose money by investing in built assets. For infrastructure projects, due to its significant cost of development and lengthy delivery time, presenting the full money story of going green is of vital importance. Traditional views of life-cycle costing tend to focus on the pure economics of a construction project. Sustainability concepts are not broadly integrated with the current LCCA in the construction sector. To rectify this problem, this paper reports on the progress to date of developing and extending contemporary LCCA models in the evaluation of road infrastructure sustainability. The suggested new model development is based on sustainability indicators identified through previous research, and incorporating industry verified cost elements of sustainability measures. The on-going project aims to design and a working model for sustainability life-cycle costing analysis for this type of infrastructure projects.

Withholding and withdrawing life-sustaining treatment : criminal responsibility for established medical practice?

The law recognises the right of a competent adult to refuse medical treatment even if this will lead to death. Guardianship and other legislation also facilitates the making of decisions to withhold or withdraw life-sustaining treatment in certain circumstances. Despite this apparent endorsement that such decisions can be lawful, doubts have been raised in Queensland about whether decisions to withhold or withdraw life-sustaining treatment would contravene the criminal law, and particularly the duty imposed by the Criminal Code (Qld) to provide the “necessaries of life”. This article considers this tension in the law and examines various arguments that might allow for such decisions to be made lawfully. It ultimately concludes, however, that criminal responsibility may still arise and so reform is needed.

Creating and sustaining a basis for life-long learning in tertiary dancer training

This paper acknowledges the influences that a generation Y population brings to dance training methodologies and examines this impact in a tertiary context. Over the last 4 years, Queensland University of Technology has been modifying their curriculum for new students transitioning from the private dance studio into the prevocational university environment. An intensive training program was designed to empower the student creating effective entry points for common understandings in the learning and teaching of dance techniques with improved and accelerated learning outcomes. This paper shares these philosophies and practices in training for life-long learning that prepare the young dancer for longevity in the industry.

Investigating the patterns and determinants of life satisfaction in Germany following reunification

This paper investigates the patterns and determinants of life satisfaction in Germany following reunification. We implement a new fixed-effect estimator for ordinal life satisfaction in the German Socio-Economic Panel and find negative effects on life satisfaction from being recently fired, losing a spouse through either death or separation, and time spent in hospital, while we find strong positive effects from income and marriage. Using a new causal decomposition technique, we find that East Germans experienced a continued improvement in life satisfaction to which increased household incomes contributed around 12 percent. Most of the improvement is explained by better average circumstances, such as greater political freedom. For West Germans, we find little change in average life satisfaction over this period.

Quantifying the costs of drought : new evidence from life satisfaction data

We estimate the cost of droughts by matching rainfall data with individual life satisfaction. Our context is Australia over the period 2001 to 2004, which included a particularly severe drought. Using fixed-effect models, we find that a drought in spring has a detrimental effect on life satisfaction equivalent to an annual reduction in income of A$18,000. This effect, however, is only found for individuals living in rural areas. Using our estimates, we calculate that the predicted doubling of the frequency of spring droughts will lead to the equivalent loss in life satisfaction of just over 1% of GDP annually.