Imperial College London

Professor Tony Cass

Faculty of Natural SciencesDepartment of Chemistry

Professor of Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 5195t.cass

 
 
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Location

 

6.23Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

427 results found

Barr ELM, Barzi F, Hughes JT, Jerums G, Hoy WE, O'Dea K, Jones GRD, Lawton PD, Brown ADH, Thomas M, Ekinci EI, Sinha A, Cass A, MacIsaac RJ, Maple-Brown LJet al., 2018, High baseline levels of tumor necrosis factor receptor 1 are associated with progression of kidney disease in indigenous australians with diabetes: The eGFR follow-up study, Diabetes Care, Vol: 41, Pages: 739-747, ISSN: 0149-5992

© 2018 by the American Diabetes Association. OBJECTIVE To examine the association between soluble tumor necrosis factor receptor 1 (sTNFR1) levels and kidney disease progression in Indigenous Australians at high risk of kidney disease. RESEARCH DESIGN AND METHODS This longitudinal observational study examined participants aged ≥18 years recruited from > 20 sites across diabetes and/or kidney function strata. Baseline measures included sTNFR1, serum creatinine, urine albumin-to-creatinine ratio (uACR), HbA 1c , C-reactive protein (CRP), waist-to-hip ratio, systolic blood pressure, and medical history. Linear regression was used to estimate annual change in estimated glomerular filtration rate (eGFR) for increasing sTNFR1, and Cox proportional hazards were used to estimate the hazard ratio (HR) and 95% CI for developing a combined renal outcome (first of a ≥30%decline in eGFRwith a follow-up eGFR < 60 mL/min/1.73m 2 , progression to renal replacement therapy, or renal death) for increasing sTNFR1. RESULTS Over a median of 3 years, participants with diabetes (n = 194) in the highest compared with the lowest quartile of sTNFR1 experienced significantly greater eGFR decline (24.22 mL/min/1.73 m 2 /year [95% CI27.06 to 21.38]; P = 0.004), independent of baseline age, sex, eGFR, and uACR. The adjusted HR (95% CI) for participants with diabetes per doubling of sTNFR1 for the combined renal outcome (n = 32) was 3.8 (1.1-12.8; P = 0.03). No association between sTNFR1 and either renal outcome was observed for those without diabetes (n = 259). CONCLUSIONS sTNFR1 is associated with greater kidney disease progression independent of albuminuria and eGFR in Indigenous Australians with diabetes. Further research is required to assess whether TNFR1 operates independently of other metabolic factors associated with kidney disease progression.

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Barzi F, Jones GRD, Hughes JT, Lawton PD, Hoy W, O'Dea K, Jerums G, MacIsaac RJ, Cass A, Maple-Brown LJet al., 2018, Trajectories of eGFR decline over a four year period in an Indigenous Australian population at high risk of CKD-the eGFR follow up study, Clinical Biochemistry, Vol: 53, Pages: 58-64, ISSN: 0009-9120

© 2018 The Canadian Society of Clinical Chemists Being able to estimate kidney decline accurately is particularly important in Indigenous Australians, a population at increased risk of developing chronic kidney disease and end stage kidney disease. The aim of this analysis was to explore the trend of decline in estimated glomerular filtration rate (eGFR) over a four year period using multiple local creatinine measures, compared with estimates derived using centrally-measured enzymatic creatinine and with estimates derived using only two local measures. Method: The eGFR study comprised a cohort of over 600 Aboriginal Australian participants recruited from over twenty sites in urban, regional and remote Australia across five strata of health, diabetes and kidney function. Trajectories of eGFR were explored on 385 participants with at least three local creatinine records using graphical methods that compared the linear trends fitted using linear mixed models with non-linear trends fitted using fractional polynomial equations. Temporal changes of local creatinine were also characterized using group-based modelling. Analyses were stratified by eGFR ( < 60; 60–89; 90–119 and ≥ 120 ml/min/1.73 m 2 ) and albuminuria categories ( < 3 mg/mmol; 3–30 mg/mmol; > 30 mg/mmol). Results: Mean age of the participants was 48 years, 64% were female and the median follow-up was 3 years. Decline of eGFR was accurately estimated using simple linear regression models and locally measured creatinine was as good as centrally measured creatinine at predicting kidney decline in people with an eGFR < 60 and an eGFR 60–90 ml/min/1.73 m 2 with albuminuria. Analyses showed that one baseline and one follow-up locally measured creatinine may be sufficient to estimate short term (up to four years) kidney function decline. The greatest yearly decline was estimated in those with eGFR 60–90 and macro-albuminuria: −6.21 (−8.20, −4.

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Hughes JT, Dembski L, Kerrigan V, Majoni SW, Lawton PD, Cass Aet al., 2018, Gathering Perspectives - Finding Solutions for Chronic and End Stage Kidney Disease, Nephrology, Vol: 23, Pages: 5-13, ISSN: 1320-5358

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Hughes JT, Maple-Brown LJ, Thomas M, Lawton PD, Sinha A, Cass A, Barzi F, Jones GRD, Jerums G, MacIsaac RJ, O'Dea K, Hoy WEet al., 2018, Cross-sectional associations of albuminuria among Aboriginal and Torres Strait Islander adults: the eGFR Study, Nephrology, Vol: 23, Pages: 37-45, ISSN: 1320-5358

© 2016 Asian Pacific Society of Nephrology Objective: To describe the detailed associations of albuminuria among a contemporary cohort of Aboriginal and Torres Strait Islander people to inform strategies for chronic kidney disease prevention and management. Methods: A cross-sectional analysis of Indigenous participants of the eGFR Study. Measures: Clinical, biochemical and anthropometric measures were collected (including body-circumferences, blood pressure (BP); triglycerides, HbA1c, liver function tests, creatinine; urine- microscopic-haem, albumin: creatinine ratio (ACR), prescriptions- angiotensin converting enzyme inhibitor or angiotensin receptor II antagonist (ACEI/ARB). Albuminuria and diabetes were defined by an ACR > 3.0 mg/mmol, and HbA1c≥48 mmol/mol or prior history respectively. Waist: hip ratio (WHR), and estimated glomerular filtration rate (eGFR) were calculated. ACR was non-normally distributed; a logarithmic transformation was applied (in base 2), with each unit increase in log2-albuminuria representing a doubling of ACR. Results: 591 participants were assessed (71% Aboriginal, 61.6% female, mean age 45.1 years, BMI 30.2 kg/m 2 , WHR 0.94, eGFR 99.2 ml/min/1.73m 2 ). The overall prevalence of albuminuria, diabetes, microscopic-haem and ACEI/ARB use was 41.5%, 41.5%, 17.8% and 34.7% respectively; 69.3% of adults with albuminuria and diabetes received an ACEI/ARB. Using multivariable linear regression modelling, the potentially modifiable factors independently associated with log2-albuminuria were microscopic-haem, diabetes, WHR, systolic BP, alkaline phosphatase (all positive) and eGFR (inverse). Conclusion: Albuminuria is associated with diabetes, central obesity and haematuria. High ACEI/ARB prescribing for adults with diabetes and albuminuria was observed. Further understanding of the links between fat deposition, haematuria and albuminuria is required.

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Li L, Guthridge S, Li SQ, Zhao Y, Lawton P, Cass Aet al., 2018, Estimating the total prevalence and incidence of end-stage kidney disease among Aboriginal and non-Aboriginal populations in the Northern Territory of Australia, using multiple data sources, BMC Nephrology, Vol: 19

© 2018 The Author(s). Background: Most estimates for End Stage Kidney Disease (ESKD) prevalence and incidence are based on renal replacement therapy (RRT) registers. However, not all people with ESKD will commence RRT and estimates based only on RRT registry data will underestimate the true burden of ESKD in the community. This study estimates the total number of Northern Territory (NT) residents with ESKD including: those receiving RRT, those diagnosed but not receiving RRT and an estimate of "undiagnosed" cases. Methods: Four data sources were used to identify NT residents with a diagnosis of ESKD: public hospital admissions, Australia an d New Zealand Dialysis and Transplant Registry registrations, death registrations and, for the Aboriginal population only, electronic primary care records. Three data sources contained information recorded between 1 July 2008 and 31 December 2013, death registration data extended to 31 December 2014 to capture 2013 prevalent cases. A capture-recapture method was used to estimate both diagnosed and undiagnosed cases by making use of probability patterns of overlapping multiple data sources. Results: In 2013, the estimated ESKD prevalence in the NT Aboriginal population was 11.01 (95% confidence interval (CI) 10.24-11.78) per 1000, and 0.90 (95% CI 0.76-1.05) per 1000 in the NT non-Aboriginal population. The age-adjusted rates were 17.97 (95% CI 17.82-18.11) and 1.07 (95% CI 1.05-1.09) per 1000 in the NT Aboriginal and non-Aboriginal populations respectively. The proportion of individuals receiving RRT was 71.4% of Aboriginal and 75.5% of non-Aboriginal prevalent ESKD cases. The age-adjusted ESKD incidence was also greater for the Aboriginal (5.26 (95% CI 4.44-6.08) per 1000 population) than non-Aboriginal population (0.36 (95% CI 0.25-0.47) per 1000). Conclusion: This study provides comprehensive estimates of the burden of ESKD including those cases that are not identified in relevant health data sources. The result

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Morton RL, Schlackow I, Gray A, Emberson J, Herrington W, Staplin N, Reith C, Howard K, Landray MJ, Cass A, Baigent C, Mihaylova Bet al., 2018, Impact of CKD on Household Income, KIDNEY INTERNATIONAL REPORTS, Vol: 3, Pages: 610-618, ISSN: 2468-0249

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O'Brien Z, Cass A, Cole L, Finfer S, Gallagher M, McArthur C, McGuiness S, Myburgh J, Bellomo R, Mårtensson Jet al., 2018, Higher versus Lower Continuous Renal Replacement Therapy Intensity in Critically ill Patients with Liver Dysfunction, Blood Purification, Vol: 45, Pages: 36-43, ISSN: 0253-5068

© 2017 S. Karger AG, Basel. Aims: To study the association between higher versus lower continuous renal replacement therapy (CRRT) intensity and mortality in critically ill patients with combined acute kidney injury and liver dysfunction. Methods: Post-hoc analysis of patients with liver dysfunction (Sequential Organ Failure Assessment liver score ≥2 or diagnosis of liver failure/transplant) included in the Randomized Evaluation of Normal versus Augmented Level renal replacement therapy (RENAL) trial. Results: Of 444 patients, 210 (47.3%) were randomized to higher intensity (effluent flow 40 mL/kg/h) and 234 (52.7%) to lower intensity (effluent flow 25 mL/kg/h) therapy. Overall, 79 and 86% of prescribed effluent flow was delivered in the higher-intensity and lower-intensity groups, respectively (p < 0.001). In total, 113 (54.1%) and 120 (51.3%) patients died in each group. On multivariable Cox regression analysis, we found no independent association between higher CRRT intensity and mortality (HR 0.93, 95% CI 0.70-1.24; p = 0.642). Conclusions: In RENAL patients with liver dysfunction, higher CRRT intensity was not associated with reduced mortality.

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Rawson TM, O'Hare D, Herrero P, Sharma S, Moore LSP, de Barra E, Roberts JA, Gordon AC, Hope W, Georgiou P, Cass AEG, Holmes AHet al., 2018, Delivering precision antimicrobial therapy through closed-loop control systems, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 73, Pages: 835-843, ISSN: 0305-7453

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Sharma S, El-Laboudi A, Reddy M, Jugnee N, Sivasubramaniyam S, El Sharkawy M, Georgiou P, Johnston D, Oliver N, Cass AEGet al., 2018, A pilot study in humans of microneedle sensor arrays for continuous glucose monitoring, ANALYTICAL METHODS, Vol: 10, Pages: 2088-2095, ISSN: 1759-9660

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Storey BC, Staplin N, Haynes R, Reith C, Emberson J, Herrington WG, Wheeler DC, Walker R, Fellström B, Wanner C, Landray MJ, Baigent C, Storey BC, Staplin N, Haynes R, Reith C, Emberson J, Herrington WG, Wheeler DC, Walker R, Fellström B, Wanner C, Landray MJ, Baigent C, Tomson C, Krane V, Cass A, Craig J, Neal B, Jiang L, Hooi LS, Levin A, Agodoa L, Gaziano M, Kasiske B, Massy ZA, Feldt-Rasmussen B, Krairittichai U, Ophascharoensuk V, Holdaas H, Tesar V, Wiecek A, Grobbee D, de Zeeuw D, Grönhagen-Riska C, Dasgupta T, Lewis D, Herrington W, Mafham M, Majoni W, Wallendszus K, Grimm R, Pedersen T, Tobert J, Armitage J, Baxter A, Bray C, Chen Y, Chen Z, Hill M, Knott C, Parish S, Simpson D, Sleight P, Young A, Collins Ret al., 2018, Lowering LDL cholesterol reduces cardiovascular risk independently of presence of inflammation, Kidney International, Vol: 93, Pages: 1000-1007, ISSN: 0085-2538

© 2017 International Society of Nephrology Markers of inflammation, including plasma C-reactive protein (CRP), are associated with an increased risk of cardiovascular disease, and it has been suggested that this association is causal. However, the relationship between inflammation and cardiovascular disease has not been extensively studied in patients with chronic kidney disease. To evaluate this, we used data from the Study of Heart and Renal Protection (SHARP) to assess associations between circulating CRP and LDL cholesterol levels and the risk of vascular and non-vascular outcomes. Major vascular events were defined as nonfatal myocardial infarction, cardiac death, stroke or arterial revascularization, with an expanded outcome of vascular events of any type. Higher baseline CRP was associated with an increased risk of major vascular events (hazard ratio per 3x increase 1.28; 95% confidence interval 1.19-1.38). Higher baseline LDL cholesterol was also associated with an increased risk of major vascular events (hazard ratio per 0.6 mmol/L higher LDL cholesterol; 1.14, 1.06-1.22). Higher baseline CRP was associated with an increased risk of a range of non-vascular events (1.16, 1.12-1.21), but there was a weak inverse association between baseline LDL cholesterol and non-vascular events (0.96, 0.92-0.99). The efficacy of lowering LDL cholesterol with simvastatin/ezetimibe on major vascular events, in the randomized comparison, was similar irrespective of CRP concentration at baseline. Thus, decisions to offer statin-based therapy to patients with chronic kidney disease should continue to be guided by their absolute risk of atherosclerotic events. Estimation of such risk may include plasma biomarkers of inflammation, but there is no evidence that the relative beneficial effects of reducing LDL cholesterol depends on plasma CRP concentration.

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Weisbord SD, Gallagher M, Jneid H, Garcia S, Cass A, Thwin SS, Conner TA, Chertow GM, Bhatt DL, Shunk K, Parikh CR, McFalls EO, Brophy M, Ferguson R, Wu H, Androsenko M, Myles J, Kaufman J, Palevsky PMet al., 2018, Outcomes after angiography with sodium bicarbonate and acetylcysteine, New England Journal of Medicine, Vol: 378, Pages: 603-614, ISSN: 0028-4793

Copyright © 2017 Massachusetts Medical Society. BACKGROUND: Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy. METHODS: Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary end point. RESULTS: The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P = 0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P = 0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P = 0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury. CONCLUSIONS: Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department

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Angell B, Laba TL, Lung T, Brown A, Eades S, Usherwood T, Peiris D, Billot L, Hillis G, Webster R, Tonkin A, Reid C, Molanus B, Rafter N, Cass A, Patel A, Jan Set al., 2017, Healthcare expenditure on Indigenous and non-Indigenous Australians at high risk of cardiovascular disease, International Journal for Equity in Health, Vol: 16

© 2017 The Author(s). Background: In spite of bearing a heavier burden of death, disease and disability, there is mixed evidence as to whether Indigenous Australians utilise more or less healthcare services than other Australians given their elevated risk level. This study analyses the Medicare expenditure and its predictors in a cohort of Indigenous and non-Indigenous Australians at high risk of cardiovascular disease. Methods: The healthcare expenditure of participants of the Kanyini Guidelines Adherence with the Polypill (GAP) pragmatic randomised controlled trial was modelled using linear regression methods. 535 adult (48% Indigenous) participants at high risk of cardiovascular disease (CVD) were recruited through 33 primary healthcare services (including 12 Aboriginal Medical Services) across Australia. Results: There was no significant difference in the expenditure of Indigenous and non-Indigenous participants in non-remote areas following adjustment for individual characteristics. Indigenous individuals living in remote areas had lower MBS expenditure (932 per year P < 0.001) than other individuals. MBS expenditure was found to increase with being aged over 65 years (128, p = 0.013), being female (472, p = 0.003), lower baseline reported quality of life (102 per 0.1 decrement of utility p = 0.004) and a history of diabetes (324, p = 0.001), gout (631, p = 0.022), chronic obstructive pulmonary disease (469, p = 0.019) and established CVD whether receiving guideline-recommended treatment prior to the trial (452, p = 0.005) or not (483, p = 0.04). When controlling for all other characteristics, morbidly obese patients had lower MBS expenditure than other individuals (-887, p = 0.002). Conclusion: The findings suggest that for the majority of participants, once individuals are engaged with a primary care provider, factors other than whether they are Indigenous determine the level of Medicare expenditure for each person. Trial registration: Australian Ne

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Barr EL, Maple-Brown LJ, Barzi F, Hughes JT, Jerums G, Ekinci EI, Ellis AG, Jones GR, Lawton PD, Sajiv C, Majoni SW, Brown AD, Hoy WE, O'Dea K, Cass A, MacIsaac RJet al., 2017, Comparison of creatinine and cystatin C based eGFR in the estimation of glomerular filtration rate in Indigenous Australians: The eGFR Study, Clinical Biochemistry, Vol: 50, Pages: 301-308, ISSN: 0009-9120

© 2016 The Canadian Society of Clinical Chemists Background The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation that combines creatinine and cystatin C is superior to equations that include either measure alone in estimating glomerular filtration rate (GFR). However, whether cystatin C can provide any additional benefits in estimating GFR for Indigenous Australians, a population at high risk of end-stage kidney disease (ESKD) is unknown. Methods Using a cross-sectional analysis from the eGFR Study of 654 Indigenous Australians at high risk of ESKD, eGFR was calculated using the CKD-EPI equations for serum creatinine (eGFRcr), cystatin C (eGFRcysC) and combined creatinine and cystatin C (eGFRcysC + cr). Reference GFR (mGFR) was determined using a non-isotopic iohexol plasma disappearance technique over 4 h. Performance of each equation to mGFR was assessed by calculating bias, % bias, precision and accuracy for the total population, and according to age, sex, kidney disease, diabetes, obesity and c-reactive protein. Results Data were available for 542 participants (38% men, mean [sd] age 45 [14] years). Bias was significantly greater for eGFRcysC (15.0 mL/min/1.73 m 2 ; 95% CI 13.3–16.4, p  <  0.001) and eGFRcysC + cr (10.3; 8.8–11.5, p  <  0.001) compared to eGFRcr (5.4; 3.0–7.2). Accuracy was lower for eGFRcysC (80.3%; 76.7–83.5, p  <  0.001) but not for eGFRcysC + cr (91.9; 89.3–94.0, p = 0.29) compared to eGFRcr (90.0; 87.2–92.4). Precision was comparable for all equations. The performance of eGFRcysC deteriorated across increasing levels of c-reactive protein. Conclusion Cystatin C based eGFR equations may not perform well in populations with high levels of chronic inflammation. CKD-EPI eGFR based on serum creatinine remains the preferred equation in Indigenous Australians.

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Cass AEG, Sharma S, 2017, Microneedle Enzyme Sensor Arrays for Continuous In Vivo Monitoring, ENZYMES AS SENSORS, Vol: 589, Pages: 413-427, ISSN: 0076-6879

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De Dassel JL, Ralph AP, Cass A, 2017, A systematic review of adherence in Indigenous Australians: An opportunity to improve chronic condition management, BMC Health Services Research, Vol: 17

© 2017 The Author(s). Background: Indigenous Australians experience high rates of chronic conditions. It is often asserted Indigenous Australians have low adherence to medication; however there has not been a comprehensive examination of the evidence. This systematic literature review presents data from studies of Indigenous Australians on adherence rates and identifies supporting factors and impediments from the perspective of health professionals and patients. Methods: Search strategies were used to identify literature in electronic databases and websites. The following databases were searched: Scopus, Medline, CINAHL Plus, PsycINFO, Academic Search Premier, Cochrane Library, Trove, Indigenous Health infonet and Grey Lit.org. Articles in English, reporting original data on adherence to long-term, self-administered medicines in Australia's Indigenous populations were included. Data were extracted into a standard template and a quality assessment was undertaken. Results: Forty-seven articles met inclusion criteria. Varied study methodologies prevented the use of meta-analysis. Key findings: health professionals believe adherence is a significant problem for Indigenous Australians; however, adherence rates are rarely measured. Health professionals and patients often reported the same barriers and facilitators, providing a framework for improvement. Conclusions: There is no evidence that medication adherence amongst Indigenous Australians is lower than for the general population. Nevertheless, the heavy burden of morbidity and mortality faced by Indigenous Australians with chronic conditions could be alleviated by enhancing medication adherence. Some evidence supports strategies to improve adherence, including the use of dose administration aids. This evidence should be used by clinicians when prescribing, and to implement and evaluate programs using standard measures to quantify adherence, to drive improvement in health outcomes.

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Devitt J, Anderson K, Cunningham J, Preece C, Snelling P, Cass Aet al., 2017, Difficult conversations: Australian Indigenous patients' views on kidney transplantation, BMC Nephrology, Vol: 18

© 2017 The Author(s). Background: Indigenous Australians suffer a disproportionate burden of end stage kidney disease (ESKD) but are significantly less likely to receive a transplant. This study explores Indigenous ESKD patients' views on transplantation as a treatment option. Methods: The Improving Access to Kidney Transplants (IMPAKT) research program investigated barriers to kidney transplantation for Indigenous Australians. An interview study, conducted in 2005-2006, elicited illness experience narratives from 146 Indigenous patients, including views on transplant. Interviews were conducted at 26 sites that collectively treat the majority of Indigenous ESKD patients. Key themes were identified via team consensus meetings, providing a flexible framework and focus for continued coding. Results: Four inter-related themes were identified in patient commentary: a very high level (90% of respondents) of positive interest in transplantation; patients experienced a range of communication difficulties and felt uninformed about transplant; family involvement in decision-making was constrained by inadequate information; and patients needed to negotiate cultural and social sensitivities around transplantation. Conclusions: Indigenous ESKD patients demonstrated an intense interest in transplantation preferring deceased over living kidney donation. Patients believe transplant is the path most likely to support the re-establishment of their 'normal' family life. Patients described themselves as poorly informed; most had only a rudimentary knowledge of the notion of transplant but no understanding of eligibility criteria, the transplant procedure and associated risks. Patients experienced multiple communication barriers that - taken together - undermine their engagement in treatment decision-making. Families and communities are disempowered because they also lack information to reach a shared understanding of transplantation. Cultural sensitivities associated with transpla

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Gorham G, Howard K, Togni S, Lawton P, Hughes J, Majoni SW, Brown S, Barnes S, Cass Aet al., 2017, Economic and quality of care evaluation of dialysis service models in remote Australia: Protocol for a mixed methods study, BMC Health Services Research, Vol: 17

© 2017 The Author(s). Background: Australia's Northern Territory (NT) has the country's highest incidence and prevalence of kidney disease. Indigenous people from remote areas suffer the heaviest disease burden. Concerns regarding cost and sustainability limit the provision of dialysis treatments in remote areas and most Indigenous people requiring dialysis relocate to urban areas. However, this dislocation of people from their family, community and support networks may prove more costly when the broade r health, societal and economic consequences for the individual, family and whole of government are considered. Methods: The Dialysis Models of Care Study is a large cross organisation mixed methods study. It includes a retrospective (2000-2014) longitudinal data linkage study of two NT cohorts: Renal Cohort 1- comprising approximately 2000 adults who received dialysis and Renal Cohort 2- comprising approximately 400 children of those adults. Linkage of administrative data sets from the Australian and New Zealand Dialysis and Transplant Registry, NT Departments of Health, Housing and Education by a specialist third party (SA/NT Datalink) will enable extraction of activity, financial and outcome data. Interviews with patients, clinicians and service providers, using a snowball technique, will canvass relevant issues and assist in determining the full costs and impacts of the five most used dialysis Models of Care. Discussion: The study uses a mixed methods approach to investigate the quantitative and qualitative dimensions of the full costs and outcomes associated with the choice of particular dialysis models of care for any given patient. The study includes a large data linkage component that for the first time links health, housing and education data to fully analyse and evaluate the impact on patients, their families and the broader community, resulting from the relocation of people for treatment. The study will generate a large amount of activity, financial a

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Gummer J, Trengove R, Pascoe EM, Badve SV, Cass A, Clarke P, McDonald SP, Morrish AT, Pedagogos E, Perkovic V, Reidlinger D, Scaria A, Walker R, Vergara LA, Hawley CM, Johnson DW, Olynyk JK, Ferrari Pet al., 2017, Association between serum hepcidin-25 and primary resistance to erythropoiesis-stimulating agents in chronic kidney disease: a secondary analysis of the HERO trial, Nephrology, Vol: 22, Pages: 548-554, ISSN: 1320-5358

© 2016 Asian Pacific Society of Nephrology Background: Pentoxifylline has been shown to increase haemoglobin levels in patients with chronic kidney disease (CKD) and erythropoietin-stimulating agent (ESA)-hyporesponsive anaemia in the Handling Erythropoietin Resistance with Oxpentifylline multicentre double-blind, randomized controlled trial. The present sub-study evaluated the effects of pentoxifylline on the iron-regulatory hormone hepcidin in patients with ESA-hyporesponsive CKD. Methods: This sub-study included 13 patients in the pentoxifylline arm (400 mg daily) and 13 in the matched placebo arm. Hepcidin-25 was measured by ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry following isolation from patient serum. Serum hepcidin-25, serum iron biomarkers, haemoglobin and ESA dosage were compared within and between the two groups. Results: Hepcidin-25 concentration at 4 months adjusted for baseline did not differ significantly in pentoxifylline versus placebo treated patients (adjusted mean difference (MD) −7.9 nmol, P = 0.114), although the difference between the groups mean translated into a > 25% reduction of circulating hepcidin-25 due to pentoxifylline compared with the placebo baseline. In paired analysis, serum hepcidin-25 levels were significantly decreased at 4 months compared with baseline in the pentoxifylline group (−5.47 ± 2.27 nmol/l, P < 0.05) but not in the placebo group (2.82 ± 4.29 nmol/l, P = 0.24). Pentoxifylline did not significantly alter serum ferritin (MD 55.4 mcg/l), transferrin saturation (MD 4.04%), the dosage of ESA (MD −9.93 U/kg per week) or haemoglobin concentration (MD 5.75 g/l). Conclusion: The reduction of circulating hepcidin-25 due to pentoxifylline did not reach statistical significance; however, the magnitude of the difference suggests that pentoxifylline may be a clinically and biologically meaningful modulator of hepcidin-25 in dialysis of patien

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Harris-Birtill D, Singh M, Zhou Y, Shah A, Ruenraroengsak P, Gallina ME, Hanna GB, Cass AEG, Porter AE, Bamber J, Elson DSet al., 2017, Gold nanorod reshaping in vitro and in vivo using a continuous wave laser, PLOS ONE, Vol: 12, ISSN: 1932-6203

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Hughes JT, Barzi F, Hoy WE, Jones GRD, Rathnayake G, Majoni SW, Thomas MAB, Sinha A, Cass A, MacIsaac RJ, O'Dea K, Maple-Brown LJet al., 2017, Bilirubin concentration is positively associated with haemoglobin concentration and inversely associated with albumin to creatinine ratio among Indigenous Australians: eGFR Study, Clinical Biochemistry, Vol: 50, Pages: 1040-1047, ISSN: 0009-9120

© 2017 The Canadian Society of Clinical Chemists Low serum bilirubin concentrations are reported to be strongly associated with cardio-metabolic disease, but this relationship has not been reported among Indigenous Australian people who are known to be at high risk for diabetes and chronic kidney disease (CKD). Hypothesis: serum bilirubin will be negatively associated with markers of chronic disease, including CKD and anaemia among Indigenous Australians. Method: A cross-sectional analysis of 594 adult Aboriginal and Torres Strait Islander (TSI) people in good health or with diabetes and markers of CKD. Measures included urine albumin: creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), haemoglobin (Hb) and glycated haemoglobin (HbA1c). Diabetes was defined by medical history, medications or HbA1c ≥ 6.5% or ≥ 48 mmol/mol. Anaemia was defined as Hb < 130 g/L or < 120 g/L in males and females respectively. A multivariate regression analysis examining factors independently associated with log-bilirubin was performed. Results: Participants mean (SD) age was 45.1 (14.5) years, and included 62.5% females, 71.7% Aboriginal, 41.1% with diabetes, 16.7% with anaemia, 41% with ACR > 3 mg/mmol and 18.2% with eGFR < 60 mL/min/1.73m 2 . Median bilirubin concentration was lower in females than males (6 v 8 μmol/L, p < 0.001) and in Aboriginal than TSI participants (6 v 9.5 μmol/L, p < 0.001). Six factors explained 35% of the variance of log-bilirubin; Hb and cholesterol (both positively related) and ACR, triglycerides, Aboriginal ethnicity and female gender (all inversely related). Conclusion: Serum bilirubin concentrations were positively associated with Hb and total cholesterol, and inversely associated with ACR. Further research to determine reasons explaining lower bilirubin concentrations among Aboriginal compared with TSI participants are needed.

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Irish AB, Viecelli AK, Hawley CM, Hooi LS, Pascoe EM, Paul-Brent PA, Badve SV, Mori TA, Cass A, Kerr PG, Voss D, Ong LM, Polkinghorne KRet al., 2017, Effect of fish oil supplementation and aspirin use on arteriovenous fistula failure in patients requiring hemodialysis: A randomized clinical trial, Nieren- und Hochdruckkrankheiten, Vol: 46, Pages: 172-173, ISSN: 0300-5224

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Irish AB, Viecelli AK, Hawley CM, Hooi LS, Pascoe EM, Paul-Brent PA, Badve SV, Mori TA, Cass A, Kerr PG, Voss D, Ong LM, Polkinghorne KRet al., 2017, Effect of fish oil supplementation and aspirin use on arteriovenous fistula failure in patients requiring hemodialysis a randomized clinical trial, JAMA Internal Medicine, Vol: 177, Pages: 184-193, ISSN: 2168-6106

IMPORTANCE Vascular access dysfunction is a leading cause of morbidity and mortality in patients requiring hemodialysis. Arteriovenous fistulae are preferred over synthetic grafts and central venous catheters due to superior long-term outcomes and lower health care costs, but increasing their use is limited by early thrombosis and maturation failure. ?-3 Polyunsaturated fatty acids (fish oils) have pleiotropic effects on vascular biology and inflammation and aspirin impairs platelet aggregation, which may reduce access failure. OBJECTIVE To determine whether fish oil supplementation (primary objective) or aspirin use (secondary objective) is effective in reducing arteriovenous fistula failure. DESIGN, SETTING, AND PARTICIPANTS The Omega-3 Fatty Acids (Fish Oils) and Aspirin in Vascular Access Outcomes in Renal Disease (FAVOURED) study was a randomized, double-blind, controlled clinical trial that recruited participants with stage 4 or 5 chronic kidney disease from 2008 to 2014 at 35 dialysis centers in Australia, Malaysia, New Zealand, and the United Kingdom. Participants were observed for 12 months after arteriovenous fistula creation. INTERVENTIONS Participants were randomly allocated to receive fish oil (4 g/d) or matching placebo. A subset (n = 406) was also randomized to receive aspirin (100mg/d) or matching placebo. Treatment started 1 day prior to surgery and continued for 12 weeks. MAIN OUTCOMES AND MEASURES The primary outcomewas fistula failure, a composite of fistula thrombosis and/or abandonment and/or cannulation failure, at 12 months. Secondary outcomes included the individual components of the primary outcome. RESULTS Of 1415 eligible participants, 567 were randomized (359 [63%] male, 298 [53%] white, 264 [47%] with diabetes; mean [SD] age, 54.8 [14.3] y). The same proportion of fistula failures occurred in the fish oil and placebo arms (128 of 270 [47%] vs 125 of 266 [47%]; relative risk [RR] adjusted for aspirin use, 1.03; 95%CI, 0.86-1.23; P =

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Jardine MJ, Zuo L, Gray NA, De Zoysa JR, Chan CT, Gallagher MP, Monaghan H, Grieve SM, Puranik R, Lin H, Eris JM, Zhang L, Xu J, Howard K, Lo S, Cass A, Perkovic Vet al., 2017, A trial of extending hemodialysis hours and quality of life, Journal of the American Society of Nephrology, Vol: 28, Pages: 1898-1911, ISSN: 1046-6673

© 2017 by the American Society of Nephrology. The relationship between increased hemodialysis hours and patient outcomes remains unclear. We randomized (1:1) 200 adult recipients of standard maintenance hemodialysis from in-center and home-based hemodialysis programs to extendedweekly ($24 hours) or standard (target 12-15 hours, maximum18 hours) hemodialysis hours for 12 months. The primary outcome was change in quality of life from baseline assessed by the EuroQol 5 dimension instrument (3 level) (EQ-5D). Secondary outcomes included medication usage, clinical laboratory values, vascular access events, and change in left ventricularmass index. At 12months, median weekly hemodialysis hours were 24.0 (interquartile range, 23.6-24.0) and 12.0 (interquartile range, 12.0-16.0) in the extended and standard groups, respectively. Change in EQ-5D score at study end did not differ between groups (mean difference, 0.04 [95% confidence interval, 20.03 to 0.11]; P=0.29). Extended hours were associated with lower phosphate and potassium levels and higher hemoglobin levels. Blood pressure (BP) did not differ between groups at study end. Extended hourswere associatedwith fewer BP-lowering agents and phosphate-bindingmedications, but were not associated with erythropoietin dosing. In a substudy with 95 patients,wedetected no differencebetween groups in left ventricularmass index (meandifference,26.0 [95%confidenceinterval,214.8 to 2.7] g/m2;P=0.18).Fivedeaths occurred in the extended group and two in the standard group (P=0.44); two participants in each group withdrew consent. Similar numbers of patients experienced vascular access events in the twogroups. Thus, extendingweekly hemodialysis hours did not alter overall EQ-5D quality of life score, but was associated with improvement in some laboratory parameters and reductions in medication burden. (Clinicaltrials.gov identifier: NCT00649298).

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Kotwal S, Gallagher M, Cass A, Webster Aet al., 2017, Effects of health service geographic accessibility in patients with treated end stage kidney disease: Cohort study 2000–2010, Nephrology, Vol: 22, Pages: 1008-1016, ISSN: 1320-5358

© 2016 Asian Pacific Society of Nephrology Aim: Patients in rural areas experience poor access to health services. There are limited data on patterns of health service utilization in rural patients treated with renal replacement therapy (RRT). Methods: All prevalent patients over the age of 18 and resident in New South Wales who were receiving RRT on 01/07/2000 and incident patients who started RRT between 01/07/2000 up until 31/07/2010 were included in the study. The Accessibility Remoteness Index of Australia was used to measure rurality and to categorize participant postcode of residence at the time of their first use of a New South Wales healthcare facility after the start of RRT. We assessed (1) rates of hospitalization, (2) rates of inter-hospital transfer (IHT), (3) length of hospital stay (LOS) and (4) survival. Day-only and dialysis admissions were excluded. Negative binomial regression was used to calculate incidence rate ratios (IRR) for hospitalizations, IHT and LOS. Cox proportional hazards was used to calculate hazard ratios (HR) for survival. Results: Of the 10 505 patients included in the analysis, 1527 (15%) were rural residents while 8978 (85%) resided in urban areas. Median follow up time from start of RRT/study to end of study/death was 4.2 years (IQR 2.0 to 8.2). After allowing for differences in baseline characteristics, rural residence increased the rates of hospitalization by 8% (IRR 1.08: 95% CI 1.01–1.15; P = 0.02), rates of IHT by 176% (IRR 2.76: 95% CI 2.44–3.13; P  <  0.001) and the hazard of death by 14% (HR 1.14 95% CI: 1.05–1.24; P = 0.003) LOS was similar (Median 4.0; P = 0.07). Conclusions: Rural residents receiving RRT have higher hospitalization rates, markedly higher rates of IHT and higher long-term mortality compared with their urban counterparts.

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Kotwal S, Ranasinghe I, Brieger D, Clayton PA, Cass A, Gallagher Met al., 2017, The influence of chronic kidney disease and age on revascularization rates and outcomes in acute myocardial infarction - a cohort study, European heart journal. Acute cardiovascular care, Vol: 6, Pages: 291-298

BACKGROUND: There is a paucity of data on the complex interaction between chronic kidney disease, age and its impact on management and outcomes in acute myocardial infarction. METHODS: A state based claims dataset that collects data on all hospitalizations (representing 32.3% of the Australian population) was used to identify all patients admitted with a principal diagnosis of acute myocardial infarction (ICD10 codes: I21.0-I21.4) over a four-year period. Patients were linked to the state death registry and followed until death or end of follow-up (31 December 2009). Chronic kidney disease was defined as the presence of any of 65 ICD10 diagnostic codes for chronic kidney disease. The primary outcomes were receipt of revascularization, length of hospital stay and mortality adjusted for age, comorbidities and prior revascularization at presentation. RESULTS: Of the 40,472 patients with acute myocardial infarction, chronic kidney disease was present in 4814 patients (11.9%). Median follow-up was 2.8 years (range 0-5.5 years). In the multivariable model, there was a marked interaction between chronic kidney disease and age ( p < 0.001). Chronic kidney disease was a powerful marker of lower revascularization rates (median age group of 70-79 years: odds ratio 0.68; 95% confidence interval 0.59-0.78; p < 0.001), especially in those over the age of 50 years. The impact of chronic kidney disease on length of stay (median age group of 70-79 years vs. referent age group 18-39 years: incidence rate ratio 1.41; 95% confidence interval 1.32-1.51; p < 0.001) and long-term mortality (median age group of 70-79 years: hazard ratio 2.19; 95% confidence interval 2.01-2.39; p < 0.001) was mitigated with increasing age. CONCLUSION: Chronic kidney disease is an important deterrent for the receipt of revascularization in older patients, but age is the primary determinant of length of stay and mortality.

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Larkins N, Teixeira-Pinto A, Banks E, Gunasekera H, Cass A, Kearnes J, Craig JCet al., 2017, Blood pressure among Australian Aboriginal children, Journal of Hypertension, Vol: 35, Pages: 1801-1807, ISSN: 0263-6352

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. Objectives: To determine the prevalence of elevated blood pressure (BP) and potential predictors of SBP and DBP in urban Australian aboriginal children. Methods: The Study of Environment on Aboriginal Resilience and Child Health is a prospective cohort study of urban Aboriginal children attending four Aboriginal Community Controlled Health Services in New South Wales, Australia. Clinical measures included a manual BP measured by research officers using standardized protocols. BP z-scores adjusted for sex, age, and height were used in regression analyses. Hypertension was defined as a BP at least 95th centile and prehypertension at least 90th centile. Factors considered in relation to BP included child (BMI, dietary history, socioeconomic status, sedentary behavior) and caregiver measures (BP and caregiver stress). Results: Overall, data from 657 children, aged 2-17 years and their caregivers, collected from 2008 to 2011, were included. Median child age was 6.3 years (interquartile range: 4.0, 9.9); 15.6% (95% confidence interval 12.2-19.1%) had hypertension and 12.3% (9.2-5.5%) prehypertension. Following adjustment, the strongest predictor of BP was caregiver BP (0.15 increase in systolic z-score per 10 mmHg of caregiver BP, 95% confidence interval 0.07-0.24, P < 0.001); child BMI z-score was significantly related to diastolic [0.08 increase (0.01-0.15) per mg/m 2 BMI increase, P = 0.03] but not SBP [0.08 increase (-0.01 to 0.16) per mg/m 2 BMI increase, P = 0.08] . None of the other factors examined were significantly related to BP. Conclusion: BP is frequently elevated in urban aboriginal children. The strongest predictors of BP were caregiver BP and child BMI. Based on these data, and given the strong community linkages of aboriginal people, we recommend family-based interventions to reduce BP in this high-risk group.

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Lawton PD, McDonald SP, Snelling PL, Hughes J, Cass Aet al., 2017, Organ Transplantation in Australia: Inequities in Access and Outcome for Indigenous Australians, Transplantation, Vol: 101, Pages: e345-e346, ISSN: 0041-1337

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Le TT, Chang P, Benton DJ, McCauley JW, Iqbal M, Cass AEGet al., 2017, Dual Recognition Element Lateral Flow Assay Toward Multiplex Strain Specific Influenza Virus Detection, ANALYTICAL CHEMISTRY, Vol: 89, Pages: 6781-6786, ISSN: 0003-2700

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Lo C, Jun M, Badve SV, Pilmore H, White SL, Hawley C, Cass A, Perkovic V, Zoungas Set al., 2017, Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients, Cochrane Database of Systematic Reviews, Vol: 2017

© 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Background: Kidney transplantation is the preferred form of kidney replacement therapy for patients with end-stage kidney disease (ESKD) and is often complicated by worsening or new-onset diabetes. Management of hyperglycaemia is important to reduce post-transplant and diabetes-related complications. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. Objectives: To evaluate the efficacy and safety of pharmacological interventions for lowering glucose levels in patients who have undergone kidney transplantation and have diabetes. Search methods: We searched the Cochrane Kidney and Transplant Specialised Register to 15 April 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria: All randomised controlled trials (RCTs), quasi-RCTs and cross-over studies examining head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in patients who have received a kidney transplant and h ave diabetes were eligible for inclusion. Data collection and analysis: Two authors independently assessed study eligibility and quality and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD) or standardised mean difference (SMD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI). Main results: We included seven studies that involved a total of 399 kidney transplant recipients. All inc

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Majoni SW, Lawton PD, Barzi F, Cass A, Hughes JTet al., 2017, Assessing the Association between Serum Ferritin, Transferrin Saturation, and C-Reactive Protein in Northern Territory Indigenous Australian Patients with High Serum Ferritin on Maintenance Haemodialysis, International Journal of Nephrology, Vol: 2017, ISSN: 2090-214X

� 2017 Sandawana William Majoni et al. Objective. To determine the significance of high serum ferritin observed in Indigenous Australian patients on maintenance haemodialysis in the Northern Territory, we assessed the relationship between ferritin and transferrin saturation (TSAT) as measures of iron status and ferritin and C-reactive protein (CRP) as markers of inflammation. Methods. We performed a retrospective cohort analysis of data from adult patients (≥18 years) on maintenance haemodialysis ( > 3 months) from 2004 to 2011. Results. There were 1568 patients. The mean age was 53.9 (11.9) years. 1244 (79.3%) were Indigenous. 44.2% (n = 693) were male. Indigenous patients were younger (mean age [52.3 (11.1) versus 57.4 (15.2), p < 0.001 ]) and had higher CRP [14.7 mg/l (7-35) versus 5.9 mg/l (1.9-17.5), p < 0.001 ], higher median serum ferritin [1069 μg/l (668-1522) versus 794.9 μg/l (558.5-1252.0), p < 0.001 ], but similar transferrin saturation [26% (19-37) versus 28% (20-38), p = 0.516 ] . We observed a small positive correlation between ferritin and TSAT (r 2 = 0.11, p < 0.001), no correlation between ferritin and CRP (r 2 = 0.001, p < 0.001), and positive association between high serum ferritin and TSAT (p < 0.001), Indigenous ethnicity (p < 0.001), urea reduction ratio (p = 0.001), and gender (p < 0.001) after adjustment in mixed regression analysis. Conclusion. Serum ferritin and TSAT may inadequately reflect iron status in this population. The high ferritin was poorly explained by inflammation.

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