“Everyone should do research”




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ORAL PRESENTATION ABSTRACTS



SESSION 1: STUDENT PRESENTATIONS Chair Professor Frank Bowden Gatenby




A1


LYMPHOCYTOPENIA AS A PROGNOSTIC MARKER FOR DIFFUSE LARGE B CELL LYMPHOMA


1, 2D Talaulikar, 2A.Choudhury, 2, 3 B Shadbolt, 4M Brown


1Department of Haematology, The Canberra Hospital, 2Australian National University Medical School, 3Department of Epidemiology, 4Department of Anatomical Pathology, The Canberra Hospital, PO Box 11, Woden ACT 2606.

u4288508@anu.edu.au


Introduction

Diffuse Large B-cell Lymphoma (DLBCL) is the commonest Non-Hodgkin Lymphoma (NHL) accounting for 80% of all aggressive lymphomas. The most commonly used tool for predicting outcomes for patients with DLBCL is the International Prognostic Index (IPI), which estimates survival from a number of negative prognostic markers present at diagnosis.


Lymphocytopenia has been reported to confer adverse outcomes in a number of haematological malignancies. A recent study has shown low lymphocyte counts to be associated with poor outcome in DLBCL. The aim of this study was to determine the incidence of lymphocytopenia at diagnosis in patients with DLBCL, and to confirm its significance as a prognostic factor, particularly in relation to the IPI.


Methods

Medical (performance status of patients, stage of disease, treatment and response) and laboratory records (full blood count) of 165 patients diagnosed with DLBCL were retrieved and analysed. Lymphocyte counts were correlated with overall survival and role as a prognostic marker independent of IPI was determined, using multivariate regression analysis.


Results

Lymphocytopenia (lymphocyte count ≤ 1 X 109/L) was noted in 35.8%; it correlated adversely with overall survival (41 months vs. 124 months, p=0.002). A Cox regression model established that the prognostic significance was independent of the IPI.


Conclusions

One third of cases of DLBCL in our study had lymphocytopenia, which correlated with poor overall survival. Lymphocyte counts have prognostic significance independent of the IPI and hence, the potential to improve the risk stratification model of IPI.


Notes:

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A2


CHARACTERISTICS OF PAEDIATRIC RETURN VISITS TO AN ED AFTER 1 YEAR.


S Robison, D Richardson.


ANUMS, The Canberra Hospital, Garran ACT 2605

Drew.richardson@act.gov.au


Aims

To examine the characteristics and predictive factors of paediatric return visits (RVs) to an emergency department over a one-year period.


Methods

Prospective observational one-year follow-up study of 0-14 year old children and their carers who presented to an emergency department in March 2005. Main outcome measures: RV rate, age of the child, age and education level of the carer, number of children cared for in the home, and birth order of the child.


Results

Of the 152 paediatric patients, 137 carers (90%) participated in the telephone questionnaire. Mean age of the child on presentation was 5.8 years and a majority were male (55%). The children were more likely to be the first-born, and living with one other child/sibling. A majority of carers were educated to at least year 12 (87.5%) and were aged between 25-44 years (83.3%). Overall RV rate (defined as self-reported return to any emergency department within one year) was 26%. Children aged 0-2 years were significantly more likely to make a RV compared to 3-14 years (p=0.04). No significant difference was found when RV rates were compared to age and education level of the carer, number of children cared for in the home, and birth order of the child.


Conclusions

Reduction in the incidence of RVs could be achieved by targeted prevention strategies directed toward mothers of children aged 0-2 years. Further study with a larger sample size could better predict who is likely to return to the ED.


Notes:

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A3


AN ECONOMIC THEORY ON JOB SATISFACTION IN NURSING


M Eggert, T Faunce.


Medical School, Australian National University, Canberra 0200

marlene.eggert@anu.edu.au


Introduction

This abstract examines the effect of hospital funding formulae and key performance indicators on registered nurses’ non-pecuniary rewards. Registered nurses express job dissatisfaction with factors such as patient care load and quality, career opportunities, psychologically unpleasant work environments, poor work-life balance and a lack of voice. The way how institutional economic drivers contribute to registered nurses’ poor non-pecuniary rewards and how this effect takes hold are examined in this presentation.


Methods

A document review to identify funding formulas, their incentives and key performance indicators. An analysis of their effect as economic drivers on clinical nursing.


Results

It is my thesis that hospital funding formulae and their associated key performance indicators negatively affect registered nurses’ non-pecuniary rewards. Productivity incentives contained in hospital funding formulae and capped budgets focus management attention on strict input controls while maximizing patient throughput. This impacts on nurses in a direct and an indirect way. The input controls directly affect nurses’ job satisfaction through reducing their service input thus reducing their service quality and the quality of their relationships with patients. They also result in inadequate career prospects, unsatisfactory work-life balance and a lack of organizational voice. Management’s input control/output maximization focus results in poor investment in organizational capability and this affects nurses directly and indirectly. The direct effect is an increase in nurses’ workload through process inefficiencies. Indirectly they affect the profession because the service is left unsupported by adequate human resource and other information systems.


Conclusion

There is evidence that nurses’ services and work-life balance are negatively affected by currently used funding formulas. Redesigning funding for process and outcome quality may have a positive effect on nursing.


Notes:

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A4


The antioxidant alpha lipoic acid prevents but does not reverse dexamethasone-induced hypertension in the rat.


SLH Ong, M Sutton, H Vohra, Y Zhang, JA Whitworth.


John Curtin School of Medical Research, Australian National University, Canberra 2601, Australia.

Sharon.Ong@anu.edu.au


Introduction:

To examine whether alpha-lipoic acid (-LA), an antioxidant with mitochondrial superoxide inhibitory properties, could prevent and reverse dexamethasone-induced hypertension (DEX-HT) in rats; and if any antihypertensive effect is mediated via mitochondrial superoxide inhibition.


Methods:

In the prevention study, male Sprague-Dawley rats were given ground food or -LA-laced ground food (10mg/rat/day) overnight for 15 days. From day 5, saline or DEX (10µg/rat/day, sc) were given for 11 days. In the reversal study, DEX was administered for 10 days and from day 4, -LA treatment was commenced. Second-daily systolic blood pressure (SBP) was recorded by tail cuff method. Thymus weight was used as a marker of glucocorticoid activity. Plasma F2-isoprostane concentration was used as a marker of oxidative stress. Kidney mitochondrial superoxide was examined with MitoSOX™ Red dye (MitoSOX) via flow cytometry.


Results:

SBP was increased by DEX (from 115±3 to 139±4mmHg, n=10, P<0.0005). -LA alone did not alter SBP. -LA prevented DEX-HT (1394 DEX, 1265mmHg -LA+DEX, n=10 each, <0.0005) but did not reverse established DEX-HT (139±4 DEX, 137±2mmHg -LA+DEX, ns). The decrease in thymus weight (484, DEX, vs 1277mg/100g body weight, saline, n=10 each, <0.0005), was not significantly altered by -LA. The increase in plasma F2-isoprostane concentration in DEX-HT (4.7±0.3 saline, n=9 vs 7.1±0.6nmol/L DEX, n=8, <0.005) was prevented by -LA treatment (7.1±0.6 DEX, n=8 vs 5.66±0.2nmol/L -LA+DEX, n=10, <0.05). MitoSOX geometric mean fluorescence intensity was not increased by DEX (22321, DEX, vs 19715, saline, n=10 each, ns) and not altered by -LA.


Conclusion:

DEX-HT in rats is prevented by -LA via a mechanism other than mitochondrial superoxide reduction.


Notes:

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A5


INTIMACY, SEXUAL RELATIONSHIPS AND MALEVOLENCE ONLINE:

A PROPOSED STUDY OF THE HEALTH AND PSYCHIATRIC EFFECTS OF VIRTUAL REALITY GAMES


D Bonner and B Raphael

Academic Unit of Psychological Medicine
Australian National University, Canberra, ACT, 2601, Australia

Daniel.Bonner@anu.edu.au


Massively Multiplayer Online Games (MMOGs) are virtual reality environments, involving online relationships, sometimes sexual in nature. These have grown in 5 years from obscurity to 20 million players worldwide and hundreds of thousands in Australia. Online emotional and sexual interactions range from appropriate friendships to paedophilia at the other end of the spectrum.


Current MMOGs exhibit so-called “immersive” aspects:


  1. Players and environments have extremely life-like appearance and movements;

  2. Multiple complex essential aspects of human relationships (e.g. families, homes, sexual relationships etc).


A questionnaire will be distributed in the second half of 2008 to a near random sample of Australians aged 16 and above, (currently in draft and yet to meet ethics approval). It will assist with answering the following hypotheses:


  1. That exposure to aggressive and malevolent individuals in MMOGs, in particular virtual sexual assault, and harassment, is correlated with adverse health effects, including post-trauma psychiatric symptoms;

  2. That cooperative elements of MMOGs, in particular friendship and appropriate intimacy, are correlated with positive health and psychiatric effects, including resilience.


Regression analysis will include a comparison of younger group (aged 16-25) and the older group (aged 25 and above).


Notes:

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SESSION 2: Chair Dr Walter Abhayaratna




A6


Two isoforms of IL-3 receptor  regulate DIfferentiation and self-renewal of haematopoietic cells


1J Chen, 1J Olsen, 1S Ford, 1S Mirza, 1A Walker, 2JM Murphy, 1IG Young


1Division of Molecular Bioscience, The John Curtin School of Medical Research,

The Australian National University, Canberra, ACT 2601, Australia, 2Division of Molecular Medicine, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia

E-mail: Jinglong.Chen@anu.edu.au

Introduction

Interleukin-3 (IL-3) is a multipotent cytokine mainly produced by activated T lymphocytes and mast cells in responses to inflammation and infection. IL-3 promotes both self-renewal and differentiation of early multi-potential progenitors. The IL-3 receptor system is composed of an IL-3-specific receptor (IL-3R) and a shared receptor (hc). In mouse, there is an extra  (IL-3). On leukemic stem cells and blasts, the expression of IL-3 receptor  is elevated suggesting a role in leukemia pathogenesis. Here we report new insights into these processes with the identification of a new isoform (SP2) of IL-3R, present in mouse and human haematopoietic cells, which lacks domain 1 of the full-length receptor (SP1).


Methods

The study employed (1) RT-PCR and Western blot to detect the endogenous SP2, (2) 125I labelled hot saturation assay to study the ligand binding and (3) FACS, light/electron microscopy and real time PCR to investigate SP2’s signalling and function.


Results

Binding assays with IL-3 mutants showed that mouse SP2 uses a different high-affinity binding mode to SP1, though both mouse and human SP2 and SP1 can stimulate IL-3-dependent growth. In IL-3-dependent differentiation models, human SP2 and SP1 gave differential effects on lineage commitment or self-renewal dependent on the cellular context suggesting that different modes of ectodomain binding may modulate intracellular signalling. In multipotential FDCP-mix, the transcription factors C/EBP and PU.1 and miRNA-15a, 223 and 181a were upregulated in cells undergoing SP2-supported differentiation compared with SP1-supported self-renewal. Similarly in leukemic M1 cells, SP2 promoted differentiation compared with SP1 and gave upregulation of PU.1 and miRNA-155 and 223.


Conclusion

These findings suggest that IL-3-promoted lineage commitment uses similar mechanisms to those of steady state haematopoiesis.


Notes

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A7


A NEW TECHNIQUE FOR REGISTRATION OF 2D X-RAY FLUOROSCOPY TO 3D CT DATA FOR ANALYSIS OF KNEE KINEMATICS


1MR Pickering, 2JM Scarvell, 2PN Smith


1Department of Electrical Engineering, UNSW @ ADFA Canberra 2600

2Trauma and Orthopaedic Research Unit, The Canberra Hospital, Canberra, 2606

m.pickering@adfa.edu.au


Introduction

To understand the functional effects of joint pathologies, a system to capture accurate real-time 3D imaging of movement is required. To address this problem, a new registration algorithm was developed to automatically determine the 3D kinematics of the knee using current imaging modalities.


Methods:

Three cadaveric knees were implanted with 1mm tantalum beads to act as gold-standard fiducial markers. The knees were flexed between 0 and 90º while fluoroscopy data was captured at a rate of 25 frames/sec and resolution of 0.5 mm/pixel. 3D CT was captured using bone and soft tissue algorithms.

For every frame of the fluoroscopy data, the 3D femur and tibia data was individually registered to the fluoroscopy images using the new algorithm. This position data was then used to generate a kinematic 3D model.


Results:

Contemporary fluoroscopy-to-CT registration techniques generally use fluoroscopy images projected onto at least two different planes (up to 18 planes). Other techniques require stochastic optimization procedures that perform in the order of 500 iterations to find the optimal 3D registration. These systems report average target registration errors (TREs) of 0.5-1.2 mm.

Our new registration technique requires only a single-plane fluoroscopy image and uses a gradient-descent optimization strategy that converges to the optimal 3D position within 20-30 iterations. The new registration algorithm is able to align the bones of the knee with an average TRE of 0.57 mm.

Up to 7 degrees of concurrent axial rotation was observed during flexion of the knees to 90º.


Conclusions:

Once it is established in vivo that this image registration technique is as accurate as current invasive methods, this method will permit real-time kinematic studies without surgery. This will enable prospective longitudinal and controlled studies of reconstruction surgery, and conservative management of joint pathologies.


Notes:

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A8


Early Metabolic changes parallel liver injury in high fat-fed foz/foz mice


1CZ Larter, 2MM Yeh, 1NC Teoh, 1M Clyne, 1J Williams, 1GC Farrell.

1ANU Medical School at The Canberra Hospital, Garran ACT. 2Department of Pathology, University of Washington, Seattle USA.

Email: Claire.larter@anu.edu.au


Steatohepatitis is a metabolic disorder associated with obesity, diabetes and decreased serum adiponectin. We previously described that foz/foz mice develop fibrosing steatohepatitis after consuming a high-fat (HF) diet for 12 months. In this study, we profiled the temporal changes in liver injury in relation to markers of metabolic syndrome in foz/foz mice. From 6-weeks age, female foz/foz and wildtype littermates were fed chow or HF diet for 2, 6, 12 and 26-weeks. After 6-weeks feeding, HF-fed foz/foz mice were heavier than controls, and both liver and adipose weight (relative to body weight) were increased. Body weight continued to increase in HF-fed foz/foz mice. However, while relative adipose mass plateauxed after 6-weeks feeding, there was a disproportionate increase in liver weight in HF-fed foz/foz, which was not observed in controls. After 12-weeks HF-feeding, foz/foz mice were diabetic and had reduced serum adiponectin levels. Serum ALT levels significantly increased at 6-weeks in HF-fed foz/foz mice and values continued to rise throughout the timecourse. In contrast, there was no ALT elevation in controls at any time-point. There was histological evidence of steatohepatitis in HF-fed foz/foz mice at 12 and 26-weeks, with steatosis, inflammation and hepatocyte ballooning observed. Pericellular fibrosis was also present in HF-fed foz/foz mice after 26-weeks. In summary, in HF-fed foz/foz mice the capacity of adipose tissue to store fat appears to plateaux at 6-12 weeks, during which time hyperinsulinaemia, hyperglycaemia and hepatomegaly develop and serum adiponectin levels fall. These metabolic changes are associated with the development of steatohepatitis.


Notes:

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A9


Recognition of the deteriorating patient reduces unplanned admissions to the intensive care unit


1I A Mitchell, 1C Van Leuvan, 1B Avard, 1N Slater, 2R Berry, 3P Lamberth, 3C McCutcheon, 2H McKay.


1Intensive Care, Building 12, Level 2, Canberra Hospital, Garran, ACT 2605

2Patient Safety and Quality Unit, ACT Health, Building 6, Level 2, Canberra Hospital, Garran ACT, 3Intensive Care, Calvary Healthcare, Bruce 2617

imogen.mitchell@act.gov.au


Introduction

Unplanned intensive care unit (ICU) admissions from the ward are often triggered by the failure to recognise and appropriately manage deteriorating patients. This is evidenced by delays in admission to the ICU (1), unexpected referrals to intensive care and unexpected deaths often being preceded by significant physiological disturbances (2). The ability to detect early deterioration in patients allows early appropriate intervention. Early intervention can reduce unplanned admissions to the ICU and unexpected deaths (3). The aim of the project was to reduce the number of unplanned ICU admissions by introducing an intervention onto four wards which included:- The implementation of a new education program "COMPASS", the introduction of a new observation chart and the use of a track and trigger system.


Methods

A four month prospective, controlled, before and after intervention trial in four wards at a district and tertiary hospital was undertaken. The ethics committee waived the need for consent. Demographic data collected on all admissions included: age, gender, and admission diagnosis. Outcome data included: frequency of observations, unplanned ICU admissions, cardiac arrests, medical emergency team reviews and hospital outcome.


Results

There were a similar number of ward admissions for the two periods (1196 and 996 respectively). The frequency of vital sign measurement increased for respiratory rate (2.7 to 4.7 per day, p<0.0001) and arterial oxygen saturation (4.3 to 6.8 per day, p=0.02) .There was a decrease in unplanned ICU admissions (21 to 5, p=0.005) and cardiac arrests (4 to 0, p=0.03). Medical emergency team reviews increased from 27 to 51 (p<0.001) and the number of hospital deaths decreased from 35 to 16 (2.9% to 1.6% of all first admissions, p=0.05).

Conclusion

A three pronged approach to the recognition of the deteriorating patient increases their detection and appears to reduce the number of unplanned admissions to ICU. This simple intervention has the potential to improve patient outcome.

References

1. An acute problem. National Confidential Enquiry into Patient Outcome and Death. http://www.ncepod.org.uk/2005.htm.

2. Hillman KM, Bristow PJ, Chey T, et al. Antecedents to hospital deaths. Inter Med J 2001; 31: 343-48

3. Bellomo R, Goldsmith D, Uchino S, Buckmaster J, Hart G, Opdam H, Silvester W, Doolan L, Gutteridge G. Prospective controlled trial of medical emergency team on postoperative morbidity and mortality rates. Crit Care Med 2004; 32: 916-921


Grant acknowledgement Supportive grant from ACT Health.


A10


MONEY TALKS: BRINGING CHLAMYDIA SCREENING TO TERTIARY STUDENTS IN THE ACT

1   2   3   4   5   6   7   8   9

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