Clinical School (Royal Melbourne Hospital) - Research Publications
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ItemAccuracy and safety of ward based pleural ultrasound in the Australian healthcare system(WILEY, 2017-04)BACKGROUND AND OBJECTIVE: Ultrasound has been shown to improve the accuracy and safety of pleural procedures. Studies to date have been performed in large, specialized units, where pleural procedures are performed by a small number of highly specialized physicians. There are no studies examining the safety and accuracy of ultrasound in the Australian healthcare system where procedures are performed by junior doctors with a high staff turnover. METHODS: We performed a retrospective review of the ultrasound database in the Respiratory Department at the Royal Melbourne Hospital to determine accuracy and complications associated pleural procedures. RESULTS: A total of 357 ultrasounds were performed between October 2010 and June 2013. Accuracy of pleural procedures was 350 of 356 (98.3%). Aspiration of pleural fluid was successful in 121 of 126 (96%) of patients. Two (0.9%) patients required chest tube insertion for management of pneumothorax. There were no recorded pleural infections, haemorrhage or viscera puncture. CONCLUSION: Ward-based ultrasound for pleural procedures is safe and accurate when performed by appropriately trained and supported junior medical officers. Our findings support this model of pleural service care in the Australian healthcare system.
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ItemPooled genome wide association detects association upstream of FCRL3 with Graves' disease(BMC, 2016-11-18)BACKGROUND: Graves' disease is an autoimmune thyroid disease of complex inheritance. Multiple genetic susceptibility loci are thought to be involved in Graves' disease and it is therefore likely that these can be identified by genome wide association studies. This study aimed to determine if a genome wide association study, using a pooling methodology, could detect genomic loci associated with Graves' disease. RESULTS: Nineteen of the top ranking single nucleotide polymorphisms including HLA-DQA1 and C6orf10, were clustered within the Major Histo-compatibility Complex region on chromosome 6p21, with rs1613056 reaching genome wide significance (p = 5 × 10-8). Technical validation of top ranking non-Major Histo-compatablity complex single nucleotide polymorphisms with individual genotyping in the discovery cohort revealed four single nucleotide polymorphisms with p ≤ 10-4. Rs17676303 on chromosome 1q23.1, located upstream of FCRL3, showed evidence of association with Graves' disease across the discovery, replication and combined cohorts. A second single nucleotide polymorphism rs9644119 downstream of DPYSL2 showed some evidence of association supported by finding in the replication cohort that warrants further study. CONCLUSIONS: Pooled genome wide association study identified a genetic variant upstream of FCRL3 as a susceptibility locus for Graves' disease in addition to those identified in the Major Histo-compatibility Complex. A second locus downstream of DPYSL2 is potentially a novel genetic variant in Graves' disease that requires further confirmation.
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ItemUnderstanding factors influencing physical activity and exercise in lung cancer: a systematic review(SPRINGER, 2017-03)PURPOSE: Despite evidence and clinical practice guidelines supporting physical activity (PA) for people with lung cancer, this evidence has not translated into clinical practice. This review aims to identify, evaluate and synthesise studies examining the barriers and enablers for patients with lung cancer to participate in PA from the perspective of patients, carers and health care providers (HCPs). METHODS: Systematic review of articles using electronic databases: MEDLINE (1950-2016), CINAHL (1982-2016), EMBASE (1980-2016), Scopus (2004-2016) and Cochrane (2016). Quantitative and qualitative studies, published in English in a peer-reviewed journal, which assessed the barriers or enablers to PA for patients with lung cancer were included. Registered-PROSPERO (CRD4201603341). RESULTS: Twenty-six studies (n = 9 cross-sectional, n = 4 case series, n = 11 qualitative) including 1074 patients, 23 carers and 169 HCPs were included. Barriers and enablers to PA were identified (6 major themes, 18 sub-themes): Barriers included patient-level factors (physical capability, symptoms, comorbidities, previous sedentary lifestyle, psychological influences, perceived relevance), HCP factors (time/knowledge to deliver information) and environmental factors (access to services, resources, timing relative to treatment). Enablers included anticipated benefits, opportunity for behaviour change and influences from HCPs and carers. CONCLUSION: This systematic review has identified the volume of literature demonstrating that barriers and enablers to PA in lung cancer are multidimensional and span diverse factors. These include patient-level factors, such as symptoms, comorbidities, sedentary lifestyle, mood and fear, and environmental factors. These factors should be considered to identify and develop suitable interventions and clinical services in attempt to increase PA in patients with lung cancer.
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ItemIntensive care discharge delay is associated with increased hospital length of stay: A multicentre prospective observational study(PUBLIC LIBRARY SCIENCE, 2017-07-27)BACKGROUND: Some patients experience a delayed discharge from the intensive care unit (ICU) where the intended and actual discharge times do not coincide. The clinical implications of this remain unclear. OBJECTIVE: To determine the incidence and duration of delayed ICU discharge, identify the reasons for delay and evaluate the clinical consequences. METHODS: Prospective multi-centre observational study involving five ICUs over a 3-month period. Delay in discharge was defined as >6 hours from the planned discharge time. The primary outcome measure was hospital length stay after ICU discharge decision. Secondary outcome measures included ICU discharge after-hours, incidence of delirium, survival to hospital discharge, discharge destination, the incidence of ICU acquired infections, revocation of ICU discharge decision, unplanned readmissions to ICU within 72 hours, review of patients admitting team after ICU discharge decision. RESULTS: A total of 955 out of 1118 patients discharged were included in analysis. 49.9% of the patients discharge was delayed. The most common reason (74%) for delay in discharge was non-availability of ward bed. The median duration of the delay was 24 hours. On univariable analysis, the duration of hospital stay from the time of ICU discharge decision was significantly higher in patients who had ICU discharge delay (Median days-5 vs 6; p = 0.003). After-hours discharge was higher in patients whose discharge was delayed (34% Vs 10%; p<0.001). There was no statistically significant difference in the other secondary outcomes analysed. Multivariable analysis adjusting for known confounders revealed delayed ICU discharge was independently associated with increased hospital length of stay. CONCLUSION: Half of all ICU patients experienced a delay in ICU discharge. Delayed discharge was associated with increased hospital length of stay.
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ItemThe role of impairment of mesenchymal stem cell function in osteoporotic bone fracture healing(SPRINGER, 2017-09)With demographic change and increasing life expectancy, osteoporotic fractures have become one of the most prevalent trauma conditions seen in daily clinical practice. A variety of factors are known to affect the rate of healing in osteoporotic conditions (e.g. both biochemical and biomechanical environment of callus cells). However, the influence of impairment of mesenchymal stem cell function in the osteoporotic condition on bone fracture healing has not been fully understood. In the present study, we develop a mathematical model that quantifies the change in biological processes within the fracture callus as a result of osteoporosis. The model includes special features of osteoporosis such as reduction in mesenchymal stem cell (MSC) number in osteoporotic bone, impaired response of osteoporotic MSCs to their biomechanical microenvironment and the effects of configuration of locking compression plate (LCP) system on healing in this context. The results presented here suggest that mechanically-mediated MSCs differentiation at early stages of healing are significantly affected under osteoporotic conditions, while it is predicted that the flexible fixation achieved by increasing bone-plate distance of LCP could alleviate the negative effects of osteoporosis on healing. The outcomes of this study could potentially lead to patient specific surgical solutions, and thus achieve optimal healing outcomes in osteoporotic conditions.
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ItemThe relationship between interfragmentary movement and cell differentiation in early fracture healing under locking plate fixation(Springer Netherlands, 2016)Interfragmentary movement (IFM) at the fracture site plays an important role in fracture healing, particularly during its early stage, via influencing the mechanical microenvironment of mesenchymal stem cells within the fracture callus. However, the effect of changes in IFM resulting from the changes in the configuration of locking plate fixation on cell differentiation has not yet been fully understood. In this study, mechanical experiments on surrogate tibia specimens, manufactured from specially formulated polyurethane, were conducted to investigate changes in IFM of fractures under various locking plate fixation configurations and loading magnitudes. The effect of the observed IFM on callus cell differentiation was then further studied using computational simulation. We found that during the early stage, cell differentiation in the fracture callus is highly influenced by fracture gap size and IFM, which in turn, is highly sensitive to locking plate fixation configuration. The computational model predicted that a small gap size (e.g. 1 mm) under a relatively flexible configuration of locking plate fixation (larger bone-plate distances and working lengths) could experience excessive strain and fluid flow within the fracture site, resulting in excessive fibrous tissue differentiation and delayed healing. By contrast, a relatively flexible configuration of locking plate fixation was predicted to improve cartilaginous callus formation and bone healing for a relatively larger gap size (e.g. 3 mm). If further confirmed by animal and human studies, the research outcome of this paper may have implications for orthopaedic surgeons in optimising the application of locking plate fixations for fractures in clinical practice.
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ItemA good resource for parents, but will clinicians use it?: Evaluation of a resource for paediatric end-of-life decision making(BMC, 2017-01-25)BACKGROUND: Communication with parents about end-of-life care and decisions is a difficult and sensitive process. The objective of the present study was to ascertain clinicians' views on the acceptability and usefulness of a handbook and web-based resource (Caring Decisions) that was designed as an aid for parents facing end-of-life decisions for their child. METHODS: Qualitative interviews were conducted with a range of health professionals who provide care to children facing life-limiting conditions. RESULTS: Data analysis confirmed the acceptability and usefulness of the resource. Two major themes were revealed: 1. Family empowerment, with sub-themes Giving words and clarity, Conversation starter, 'I'm not alone in this', and A resource to take away, highlighted how the resource filled a gap by supporting and enabling families in a multitude of ways; 2. Not just for families, with sub-themes A guide for staff, When to give the resource?, How to give the resource and Who should give the resource?, explored the significant finding that participants viewed the resource as a valuable tool for themselves, but its presence also brought into relief potential gaps in communication processes around end-of-life care. CONCLUSION: The interview data indicated the positive reception and clear value and need for this type of resource. However, it is likely that successful resource uptake will be contingent on discussion and planning around dissemination and use within the health care team.
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Iteme Analysis of Platelet-Rich Plasma Extraction Variations in Platelet and Blood Components Between 4 Common Commercial Kits(SAGE PUBLICATIONS INC, 2017-01)BACKGROUND: Platelet-rich plasma (PRP) has been extensively used as a treatment in tissue healing in tendinopathy, muscle injury, and osteoarthritis. However, there is variation in methods of extraction, and this produces different types of PRP. PURPOSE: To determine the composition of PRP obtained from 4 commercial separation kits, which would allow assessment of current classification systems used in cross-study comparisons. STUDY DESIGN: Controlled laboratory study. METHODS: Three normal adults each donated 181 mL of whole blood, some of which served as a control and the remainder of which was processed through 4 PRP separation kits: GPS III (Biomet Biologics), Smart-Prep2 (Harvest Terumo), Magellan (Arteriocyte Medical Systems), and ACP (Device Technologies). The resultant PRP was tested for platelet count, red blood cell count, and white blood cell count, including differential in a commercial pathology laboratory. Glucose and pH measurements were obtained from a blood gas autoanalyzer machine. RESULTS: Three kits taking samples from the "buffy coat layer" were found to have greater concentrations of platelets (3-6 times baseline), while 1 kit taking samples from plasma was found to have platelet concentrations of only 1.5 times baseline. The same 3 kits produced an increased concentration of white blood cells (3-6 times baseline); these consisted of neutrophils, leukocytes, and monocytes. This represents high concentrations of platelets and white blood cells. A small drop in pH was thought to relate to the citrate used in the sample preparation. Interestingly, an unexpected increase in glucose concentrations, with 3 to 6 times greater than baseline levels, was found in all samples. CONCLUSION: This study reveals the variation of blood components, including platelets, red blood cells, leukocytes, pH, and glucose in PRP extractions. The high concentrations of cells are important, as the white blood cell count in PRP samples has frequently been ignored, being considered insignificant. The lack of standardization of PRP preparation for clinical use has contributed at least in part to the varying clinical efficacy in PRP use. CLINICAL RELEVANCE: The variation of platelet and other blood component concentrations between commercial PRP kits may affect clinical treatment outcomes. There is a need for standardization of PRP for clinical use.
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ItemUndernutrition and malaria in pregnancy - a dangerous dyad?(BMC, 2016-09-19)BACKGROUND: In low-resource settings, malaria and macronutrient undernutrition are major health problems in pregnancy, contributing significantly to adverse pregnancy outcomes such as preterm birth and fetal growth restriction. Affected pregnancies may result in stillbirth and neonatal death, and surviving children are at risk of poor growth and infection in infancy, and of non-communicable diseases in adulthood. Populations exposed to macronutrient undernutrition frequently reside in malaria-endemic areas, and seasonal peaks of low food supply and malaria transmission tend to coincide. Despite these geographic and temporal overlaps, integrated approaches to these twin challenges are infrequent. DISCUSSION: This opinion article examines the current evidence for malaria-macronutrition interactions and discusses possible mechanisms whereby macronutrient undernutrition and malaria may interact to worsen pregnancy outcomes. Macronutrient undernutrition dysregulates the immune response. In pregnant women, undernutrition may worsen the already increased susceptibility to malarial infection and could impair development of protective immunity to malaria, and is likely to exacerbate the impact of placental malaria on fetal growth. Malarial infection, in turn, can drive nutritional depletion; poor gestational weight gain and weight loss in pregnancy increases the risk of adverse pregnancy outcomes. Despite a commendable number of studies and trials that, in isolation, attempt to address the challenges of malaria and undernutrition in pregnancy, few dare to venture beyond the 'single disease - single solution' paradigm. We believe that this may be a lost opportunity: researching malaria-nutrition interactions, and designing and implementing integrated interventions to prevent and treat these commonly co-existing and intertwining conditions, may markedly reduce the high burden of preterm birth and fetal growth restriction in affected areas. CONCLUSION: We call for more collaboration between researchers studying malaria and nutrition in pregnancy, and propose a research agenda to address this important twin health problem.
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ItemNo Preview AvailableQuantitative Analysis of the Ellipsoid Zone Intensity in Phenotypic Variations of Intermediate Age-Related Macular Degeneration(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2017-04)PURPOSE: Reduction of the ellipsoid zone (EZ) intensity has been reported in eyes with age-related macular degeneration (AMD). This study determined whether overall EZ intensity, in retinal locations undisturbed by pathologic features, is associated with the presence of clinical features, which are known important phenotypic risk factors for disease progression, large drusen, reticular pseudodrusen (RPD), and pigmentary abnormalities. METHODS: A horizontal B-scan through the foveola on spectral-domain optical coherence tomography (SD-OCT) was performed in both eyes of 75 participants with bilateral intermediate AMD and 10 age-similar control participants. Eyes with AMD were classified as per the presence of large drusen, RPD, and hyperpigmentary changes. The relative EZ intensity profile, up to an eccentricity of 3400 μm, was averaged over seven 1000-μm retinal segments. The association between relative EZ intensity profile over seven retinal segments and AMD pathologic features was analyzed. RESULTS: The average relative EZ intensities were significantly reduced in eyes with intermediate AMD compared to normal eyes (P ≤ 0.025) and with increasing age (P ≤ 0.020). On multivariate analyses, only the presence of hyperpigmentary changes and increasing age were significantly associated with reduced overall relative intensities (P ≤ 0.024), but not the presence of large drusen or RPD (P ≥ 0.115). CONCLUSIONS: The presence of hyperpigmentary change in the macula in association with large drusen, not large drusen alone, nor large drusen with RPD, was significantly associated with a generalised reduction in EZ intensity. Quantitative assessment of the relative EZ intensity may serve as an effective biomarker of disease severity and progression.