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.

Gender differences in the effect of fish oil on appetite, inflammation and nutritional status in haemodialysis patients

Background: Haemodialysis patients show signs of chronic inflammation and reduced appetite, which is associated with a worse clinical status and an increased mortality risk. Fish oil has anti-inflammatory properties and may be useful as a therapeutic treatment. There is limited evidence to indicate the feasibility and efficacy of this intervention in dialysis patients. The present study aimed to compare the effect of 12 weeks of supplementation with fish oil on markers of appetite and inflammation in male and female haemodialysis patients. Methods: The study was conducted in 28 haemodialysis patients. All patients were prescribed 3 g of fish oil per day for 12 weeks. Changes in appetite, plasma fatty acid profiles and inflammatory markers were measured at baseline and at 12 weeks. Results: The mean (SD) increase in percent plasma eicosapentaenoic acid was statistically significant [1.1 (0.8) to 4.1 (2.2), P < 0.001], which was a strong indicator of good adherence. There were trends towards reductions in peptide YY (−9%; P = 0.078) and an increase in subjective sensations of hunger (+12%; P = 0.406), which reflects an increase in motivation to eat. Males (n = 13) experienced a more marked increase in hunger compared to females (+23% versus −6%), which was associated with maintenance in C-reactive protein and interleukin-6, and a reduction in soluble intercellular adhesion molecule-1. Conclusions: The results obtained demonstrate meaningful trends towards improvements in subjective appetite and certain inflammatory markers (although no change in dietary intake) and this effect was more pronounced in males. However, the levels of some inflammatory markers increased in females and this requires further study. The high level of adherence achieved indicates that an intervention requiring patients to consume four fish oil capsules per day is achievable. This was a short-term study and the effects need to be confirmed in a randomised controlled trial.

Investigating the hydrodynamic performance of a gross pollutant trap

Field studies show that the internal screens in a gross pollutant trap (GPT) are often clogged with organic matter, due to infrequent cleaning. The hydrodynamic performance of a GPT with fully blocked screens was comprehensively investigated under a typical range of onsite operating conditions. Using an acoustic Doppler velocimeter (ADV), velocity profiles across three critical sections of the GPT were measured and integrated to examine the net fluid flow at each section. The data revealed that when the screens are fully blocked, the flow structure within the GPT radically changes. Consequently, the capture/retention performance of the device rapidly deteriorates. Good agreement was achieved between the experimental and the previous 2D computational fluid dynamics (CFD) velocity profiles for the lower GPT inlet flow conditions.

The capture/retention investigation of a gross pollutant trap

A technique was developed to investigate the capture/retention characteristic of a gross pollutant trap (GPT) with fully and partially blocked internal screens. Custom modified spheres of variable density filled with liquid were released into the GPT inlet and monitored at the outlet. The outlet data shows that the capture/retention performances of a GPT with fully blocked screens deteriorate rapidly. During higher flow rates, screen blockages below 68% approach maximum efficiency. At lower flow rates, the high performance trend is reversed and the variation in behaviour of pollutants with different densities becomes more noticeable. Additional experiments with a second upstream inlet configured GPT showed an improved capture/retention performance. It was also noted that the bypass allows the incoming pollutants to escape when the GPT is blocked. This useful feature prevents upstream blockages between cleaning intervals.

Adherence to fish oil intervention in patients with chronic kidney disease

Objective: With growing recognition of the role of inflammation in the development of chronic and acute disease, fish oil is increasingly used as a therapeutic agent, but the nature of the intervention may pose barriers to adherence in clinical populations. Our objective was to investigate the feasibility of using a fish oil supplement in hemodialysis patients. ---------- Design: This was a nonrandomized intervention study.---------- Setting: Eligible patients were recruited at the Hemodialysis Unit of Wesley Hospital, Brisbane, Queensland, Australia. Patients The sample included 28 maintenance hemodialysis patients out of 43 eligible patients in the unit. Exclusion criteria included patients regularly taking a fish oil supplement at baseline, receiving hemodialysis for less than 3 months, or being unable to give informed consent.---------- Intervention: Eicosapentaenoic acid (EPA) was administered at 2000 mg/day (4 capsules) for 12 weeks. Adherence was measured at baseline and weekly throughout the study according to changes in plasma EPA, and was further measured subjectively by self-report.---------- Results: Twenty patients (74%) adhered to the prescription based on changes in plasma EPA, whereas an additional two patients self-reported good adherence. There was a positive relationship between fish oil intake and change in plasma EPA. Most patients did not report problems with taking the fish oil. Using the baseline data, it was not possible to characterize adherent patients.---------- Conclusions: Despite potential barriers, including the need to take a large number of prescribed medications already, 74% of hemodialysis patients adhered to the intervention. This study demonstrated the feasibility of using fish oil in a clinical population.

The hydrodynamic and capture/retention performance of a gross pollutant trap

This research shows that gross pollutant traps (GPTs) continue to play an important role in preventing visible street waste—gross pollutants—from contaminating the environment. The demand for these GPTs calls for stringent quality control and this research provides a foundation to rigorously examine the devices. A novel and comprehensive testing approach to examine a dry sump GPT was developed. The GPT is designed with internal screens to capture gross pollutants—organic matter and anthropogenic litter. This device has not been previously investigated. Apart from the review of GPTs and gross pollutant data, the testing approach includes four additional aspects to this research, which are: field work and an historical overview of street waste/stormwater pollution, calibration of equipment, hydrodynamic studies and gross pollutant capture/retention investigations. This work is the first comprehensive investigation of its kind and provides valuable practical information for the current research and any future work pertaining to the operations of GPTs and management of street waste in the urban environment. Gross pollutant traps—including patented and registered designs developed by industry—have specific internal configurations and hydrodynamic separation characteristics which demand individual testing and performance assessments. Stormwater devices are usually evaluated by environmental protection agencies (EPAs), professional bodies and water research centres. In the USA, the American Society of Civil Engineers (ASCE) and the Environmental Water Resource Institute (EWRI) are examples of professional and research organisations actively involved in these evaluation/verification programs. These programs largely rely on field evaluations alone that are limited in scope, mainly for cost and logistical reasons. In Australia, evaluation/verification programs of new devices in the stormwater industry are not well established. The current limitations in the evaluation methodologies of GPTs have been addressed in this research by establishing a new testing approach. This approach uses a combination of physical and theoretical models to examine in detail the hydrodynamic and capture/retention characteristics of the GPT. The physical model consisted of a 50% scale model GPT rig with screen blockages varying from 0 to 100%. This rig was placed in a 20 m flume and various inlet and outflow operating conditions were modelled on observations made during the field monitoring of GPTs. Due to infrequent cleaning, the retaining screens inside the GPTs were often observed to be blocked with organic matter. Blocked screens can radically change the hydrodynamic and gross pollutant capture/retention characteristics of a GPT as shown from this research. This research involved the use of equipment, such as acoustic Doppler velocimeters (ADVs) and dye concentration (Komori) probes, which were deployed for the first time in a dry sump GPT. Hence, it was necessary to rigorously evaluate the capability and performance of these devices, particularly in the case of the custom made Komori probes, about which little was known. The evaluation revealed that the Komori probes have a frequency response of up to 100 Hz —which is dependent upon fluid velocities—and this was adequate to measure the relevant fluctuations of dye introduced into the GPT flow domain. The outcome of this evaluation resulted in establishing methodologies for the hydrodynamic measurements and gross pollutant capture/retention experiments. The hydrodynamic measurements consisted of point-based acoustic Doppler velocimeter (ADV) measurements, flow field particle image velocimetry (PIV) capture, head loss experiments and computational fluid dynamics (CFD) simulation. The gross pollutant capture/retention experiments included the use of anthropogenic litter components, tracer dye and custom modified artificial gross pollutants. Anthropogenic litter was limited to tin cans, bottle caps and plastic bags, while the artificial pollutants consisted of 40 mm spheres with a range of four buoyancies. The hydrodynamic results led to the definition of global and local flow features. The gross pollutant capture/retention results showed that when the internal retaining screens are fully blocked, the capture/retention performance of the GPT rapidly deteriorates. The overall results showed that the GPT will operate efficiently until at least 70% of the screens are blocked, particularly at high flow rates. This important finding indicates that cleaning operations could be more effectively planned when the GPT capture/retention performance deteriorates. At lower flow rates, the capture/retention performance trends were reversed. There is little difference in the poor capture/retention performance between a fully blocked GPT and a partially filled or empty GPT with 100% screen blockages. The results also revealed that the GPT is designed with an efficient high flow bypass system to avoid upstream blockages. The capture/retention performance of the GPT at medium to high inlet flow rates is close to maximum efficiency (100%). With regard to the design appraisal of the GPT, a raised inlet offers a better capture/retention performance, particularly at lower flow rates. Further design appraisals of the GPT are recommended.

Modification and validation of a microwave-assisted digestion method for subsequent ICP-MS determination of selected heavy metals in sediment and fish samples in Agusan River, Philippines

This study investigated, validated, and applied the optimum conditions for a modified microwave assisted digestion method for subsequent ICP-MS determination of mercury, cadmium, and lead in two matrices relevant to water quality, that is, sediment and fish. Three different combinations of power, pressure, and time conditions for microwave-assisted digestion were tested, using two certified reference materials representing the two matrices, to determine the optimum set of conditions. Validation of the optimized method indicated better recovery of the studied metals compared to standard methods. The validated method was applied to sediment and fish samples collected from Agusan River and one of its tributaries, located in Eastern Mindanao, Philippines. The metal concentrations in sediment ranged from 2.85 to 341.06 mg/kg for Hg, 0.05 to 44.46 mg/kg for Cd and 2.20 to 1256.16 mg/kg for Pb. The results indicate that the concentrations of these metals in the sediments rapidly decrease with distance downstream from sites of contamination. In the selected fish species, the metals were detected but at levels that are considered safe for human consumption, with concentrations of 2.14 to 6.82 μg/kg for Hg, 0.035 to 0.068 μg/kg for Cd, and 0.019 to 0.529 μg/kg for Pb.

A tale of six fish: achieving social presence through discussion forums in an offline learning environment

It is widely held, through the Socratic tradition, that discussion is at the heart of learning. Moderated discussion forums have been shown to replicate the debate, argument and verbal defence of viewpoints that we have come to expect in face-to-face learning environments and that we generally accept to underpin learning. While much has been written about discussion forums in educational settings, particularly in how to moderate and promote effective interaction with students at a distance, this paper takes a different approach. It looks at how forums may be used to support face-to-face learning in the contemporary context of the massification of on-campus classes. Further to this, it will argue for discussion forums as an indicator of social presence in the learning environment. It will cautiously conclude that, through purposeful design, this form of asynchronous communication has a valuable role to play in creating a positive and supportive environment for students entering university. Discussion forums are tools with a versatility yet to be fully exploited.