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

 

301KMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Publication Type
Year
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447 results found

O'Brien Z, Cass A, Cole L, Finfer S, Gallagher M, McArthur C, McGuiness S, Myburgh J, Bellomo R, Mårtensson Jet al., 2019, Sex and mortality in septic severe acute kidney injury, Journal of Critical Care, Vol: 49, Pages: 70-76, ISSN: 0883-9441

© 2018 Purpose: To investigate the relationship between sex and mortality and whether menopause or the intensity of renal replacement therapy (RRT) modify this relationship in patients with severe septic acute kidney injury (AKI). Materials and methods: Post-hoc analysis of patients with sepsis included in the Randomized Evaluation of Normal versus Augmented Level renal replacement therapy (RENAL) trial. Results: Of 724 patients, 458 (63.3%) were male and 266 (36.7%) were female. The mean delivered effluent flow rate was 25.6 ± 7.4 ml/kg/h (80 ± 15% of prescribed dose) in males and 27.4 ± 7.6 ml/kg/h (83 ± 15% of prescribed dose) in females (p =.01). A total of 237 (51.7%) males and 118 (44.5%) females died within 90 days of randomization (p =.06). The adjusted hazard ratio (HR) for 90-day mortality was significantly decreased in females as compared with males (HR 0.74, 95% CI 0.57 to 0.96, p =.02). The relationship between sex and mortality was not significantly altered by menopausal status (adjusted P value for interaction 0.99) or by RRT intensity allocation (adjusted P value for interaction 0.27). Conclusions: In a cohort of patients with sepsis and severe AKI, female sex was associated with improved survival. The relationship between sex and survival was not altered by menopausal status or RRT intensity.

JOURNAL ARTICLE

Bollella P, Sharma S, Cass AEG, Antiochia Ret al., 2019, Microneedle-based biosensor for minimally-invasive lactate detection, BIOSENSORS & BIOELECTRONICS, Vol: 123, Pages: 152-159, ISSN: 0956-5663

JOURNAL ARTICLE

Loh AYY, Burgess CH, Tanase DA, Ferrar G, McLachlan MA, Cass AEG, Albrecht Tet al., 2018, Electric Single-Molecule Hybridization Detector for Short DNA Fragments, ANALYTICAL CHEMISTRY, Vol: 90, Pages: 14063-14071, ISSN: 0003-2700

JOURNAL ARTICLE

Piletsky SS, Cass AEG, Piletska E, Czulak J, Piletsky SAet al., 2018, A Novel Assay Format as an Alternative to ELISA: MINA Test for Biotin, CHEMNANOMAT, Vol: 4, Pages: 1214-1222, ISSN: 2199-692X

JOURNAL ARTICLE

Mie M, Matsumoto R, Mashimo Y, Cass AEG, Kobatake Eet al., 2018, Development of drug-loaded protein nanoparticles displaying enzymatically-conjugated DNA aptamers for cancer cell targeting., Mol Biol Rep

Modification of protein-based drug carriers with tumor-targeting properties is an important area of research in the field of anticancer drug delivery. To this end, we developed nanoparticles comprised of elastin-like polypeptides (ELPs) with fused poly-aspartic acid chains (ELP-D) displaying DNA aptamers. DNA aptamers were enzymatically conjugated to the surface of the nanoparticles via genetic incorporation of Gene A* protein into the sequence of the ELP-D fusion protein. Gene A* protein, derived from bacteriophage ϕX174, can form covalent complexes with single-stranded DNA via the latter's recognition sequence. Gene A* protein-displaying nanoparticles exhibited the ability to deliver the anticancer drug paclitaxel (PTX), whilst retaining activity of the conjugated Gene A* protein. PTX-loaded protein nanoparticles displaying DNA aptamers known to bind to the MUC1 tumor marker resulted in increased cytotoxicity with MCF-7 breast cancer cells compared to PTX-loaded protein nanoparticles without the DNA aptamer modification.

JOURNAL ARTICLE

Keitaanpaa S, Thomas DP, Hefler M, Cass Aet al., 2018, Increasing Australian pharmacy's role in meeting national and international antimicrobial resistance objectives, Journal of Pharmacy Practice and Research, Vol: 48, Pages: 467-472, ISSN: 1445-937X

© 2018 The Society of Hospital Pharmacists of Australia The 2016 G20 summit recognised the threat of antimicrobial resistance as not just a health issue, but also one that poses an economic risk to many counties and requires global efforts and collaboration to tackle. Australia is already implementing strategies to mitigate the risk of antimicrobial resistance but acknowledges that newer antibiotics are not the only solution and that more needs to be done in the primary health sector. This article explains how the pharmacy profession is positioned to help meet these needs by expanding roles and activities already undertaken by pharmacies and augmenting them to help meet the national strategy around tackling antimicrobial resistance. The factors that would need to be addressed to ensure this is done in a way that strengthens the profession and promotes collaboration with other health professions on local, national and international levels are discussed.

JOURNAL ARTICLE

Lo C, Toyama T, Wang Y, Lin J, Hirakawa Y, Jun M, Cass A, Hawley CM, Pilmore H, Badve SV, Perkovic V, Zoungas Set al., 2018, Insulin and glucose-lowering agents for treating people with diabetes and chronic kidney disease., Cochrane Database Syst Rev, Vol: 9

BACKGROUND: Diabetes is the commonest cause of chronic kidney disease (CKD). Both conditions commonly co-exist. Glucometabolic changes and concurrent dialysis in diabetes and CKD make glucose-lowering challenging, increasing the risk of hypoglycaemia. Glucose-lowering agents have been mainly studied in people with near-normal kidney function. It is important to characterise existing knowledge of glucose-lowering agents in CKD to guide treatment. OBJECTIVES: To examine the efficacy and safety of insulin and other pharmacological interventions for lowering glucose levels in people with diabetes and CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 12 February 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs looking at head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in people with diabetes and CKD (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) were eligible. DATA COLLECTION AND ANALYSIS: Four authors independently assessed study eligibility, risk of bias, and quality of data and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD). 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: Forty-four studies (128 records, 13,036 participants) were included. Nine studies compared sodium glucose co-transporter-2 (SGLT2) inhibitors to placebo; 13 studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; 2 studies comp

JOURNAL ARTICLE

Khanal N, Lawton PD, Cass A, McDonald SPet al., 2018, Disparity of access to kidney transplantation by indigenous and non-indigenous Australians, Medical Journal of Australia, Vol: 209, Pages: 261-266, ISSN: 0025-729X

© 2018 AMPCo Pty Ltd. Produced with Elsevier B.V. All rights reserved. Objective: To compare the likelihood of Indigenous and non-Indigenous Australians being placed on the waiting list for transplantation of a kidney from a deceased donor; to compare the subsequent likelihood of transplantation. Design, setting and participants: Observational cohort study; analysis of data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry for patients aged 18−60 years at the start of renal replacement therapy, who commenced renal replacement therapy in Australia between 28 June 2006 and 31 December 2016. Main outcome measures: Time to wait-listing; time to kidney transplantation after wait-listing. Results: 10 839 patients met the inclusion criteria, of whom 2039 (19%) were Indigenous Australians; 217 Indigenous and 3829 non-Indigenous patients were active on the waiting list at least once during the study period. The hazard ratio (HR) for wait-listing (Indigenous v non-Indigenous patients, adjusted for patient-and disease-related factors) in the first year of renal replacement therapy varied with age and remoteness (range, 0.11 [95% CI, 0.07−0.15] to 0.36 [95% CI, 0.16−0.56]); in subsequent years the adjusted HR was 0.90 (95% CI, 0.50−1.6). The adjusted HR for transplantation during the first year of wait-listing did not differ significantly from 1.0; for subsequent years of wait-listing, however, the adjusted HR was 0.40 (95% CI, 0.29−0.55). Conclusion: Disparities between Indigenous and non-Indigenous patients with end-stage kidney disease in access to kidney transplantation are not explained by patient-or disease-related factors. Changes in policy and practice are needed to reduce these differences.

JOURNAL ARTICLE

Panagiotopoulos A, Gkouma A, Vassi A, Johnson CJ, Cass AEG, Topoglidis Eet al., 2018, Hemin Modified SnO2 Films on ITO-PET with Enhanced Activity for Electrochemical Sensing, ELECTROANALYSIS, Vol: 30, Pages: 1956-1964, ISSN: 1040-0397

JOURNAL ARTICLE

Li N, Da Silva-Gane M, Cass A, Patterson K, Yip A, Handke W, Webster AC, Morton RLet al., 2018, INTERVENTIONS TO AID EMPLOYMENT FOR PEOPLE ON DIALYSIS, NEPHROLOGY, Vol: 23, Pages: 41-41, ISSN: 1320-5358

JOURNAL ARTICLE

Rawson TM, Ming D, Gowers SA, Freeman DM, Herrero P, Georgiou P, Cass AE, O'Hare D, Holmes AHet al., 2018, Public acceptability of computer-controlled antibiotic management: An exploration of automated dosing and opportunities for implementation., J Infect

A paucity of data describing citizen perceptions of novel technologies, including those containing unsupervised computer-controlled systems is currently available. We explored citizen perceptions of using a microneedle biosensor and automated dose control system at a university public festival. Groups of citizens (from 2-6 people per group) attended a short demonstration of a microneedle biosensor and automated dosing system versus a traditional phlebotomy approach over a two-day public festival. Individual groups discussed and reached consensus on a number of short questions regarding their perceptions on the acceptability of such technology. Over the two days, 100 groups participated (56/100 day 1 and 44/100 day 2). The majority of individuals reported high acceptability of microneedle technology (median Likert score 9/10), but the majority believed that doctors should decide what dose of antibiotic is delivered (75/100; 75%). Groups concurred with the acceptability of microneedles to reduce blood tests and pain associated with them. However, concerns were reported over unsupervised computer-controlled programmes making decision about antibiotic dosing. This was driven by concerns over computer error and the inability of systems to contextualise decision making to the human and social context. Future work must consider the greater role of citizen engagement in the development of such technologies, to ensure their acceptability upon implementation in clinical practice.

JOURNAL ARTICLE

Lo C, Zimbudzi E, Teede H, Cass A, Fulcher G, Gallagher M, Kerr PG, Jan S, Johnson G, Mathew T, Polkinghorne K, Russell G, Usherwood T, Walker R, Zoungas Set al., 2018, Models of care for co-morbid diabetes and chronic kidney disease, Nephrology, Vol: 23, Pages: 711-717, ISSN: 1320-5358

© 2018 Asian Pacific Society of Nephrology Diabetes and chronic kidney disease (CKD) are two of the most prevalent co-morbid chronic diseases in Australia. The increasing complexity of multi-morbidity, and current gaps in health-care delivery for people with co-morbid diabetes and CKD, emphasize the need for better models of care for this population. Previously, proposed published models of care for co-morbid diabetes and CKD have not been co-designed with stake-holders or formally evaluated. Particular components of health-care shown to be effective in this population are interventions that: are structured, intensive and multifaceted (treating diabetes and multiple cardiovascular risk factors); involve multiple medical disciplines; improve self-management by the patient; and upskill primary health-care. Here we present an integrated patient-centred model of health-care delivery incorporating these components and co-designed with key stake-holders including specialist health professionals, general practitioners and Diabetes and Kidney Health Australia. The development of the model of care was informed by focus groups of patients and health-professionals; and semi-structured interviews of care-givers and health professionals. Other distinctives of this model of care are routine screening for psychological morbidity; patient-support through a phone advice line; and focused primary health-care support in the management of diabetes and CKD. Additionally, the model of care integrates with the patient-centred health-care home currently being rolled out by the Australian Department of Health. This model of care will be evaluated after implementation across two tertiary health services and their primary care catchment areas.

JOURNAL ARTICLE

Rawson TM, Gowers S, Rogers M, Sallabank E, Sharma S, Georgiou P, Holmes AH, Cass T, O'Hare Det al., 2018, Towards a minimally invasive device for continuous monitoring of beta-lactam antibiotics, Publisher: ELSEVIER SCI LTD, Pages: 109-109, ISSN: 1201-9712

CONFERENCE PAPER

Barr EL, Barzi F, Hughes JT, Jerums G, O'Dea K, Brown AD, Ekinci EI, Jones GR, Lawton PD, Sinha A, MacIsaac RJ, Cass A, Maple-Brown LJet al., 2018, Contribution of cardiometabolic risk factors to estimated glomerular filtration rate decline in Indigenous Australians with and without albuminuria - the eGFR Follow-up Study., Nephrology (Carlton), Vol: 23, Pages: 682-689

AIM: We assessed associations between cardiometabolic risk factors and estimated glomerular filtration rate (eGFR) decline according to baseline albuminuria to identify potential treatment targets in Indigenous Australians. METHODS: The eGFR Follow-up Study is a longitudinal cohort of 520 Indigenous Australians. Linear regression was used to estimate associations between baseline cardiometabolic risk factors and annual Chronic Kidney Disease Epidemiology Collaboration eGFR change (mL/min per 1.73m2 /year), among those classified with baseline normoalbuminuria (urine albumin-to-creatinine ratio (uACR) <3 mg/mmol; n = 297), microalbuminuria (uACR 3-30 mg/mmol; n = 114) and macroalbuminuria (uACR ≥30 mg/mmol; n = 109). RESULTS: After a median of 3 years follow-up, progressive declines of the age- and sex-adjusted mean eGFR were observed across albuminuria categories (-2.0 [-2.6 to -1.4], -2.5 [-3.7 to -1.3] and -6.3 [-7.8 to -4.9] mL/min per 1.72m2 /year). Although a borderline association was observed between greater baseline haemoglobin A1c and eGFR decline in those with macroalbuminuria (P = 0.059), relationships were not significant in those with microalbuminuria (P = 0.187) or normoalbuminuria (P = 0.23). Greater baseline blood pressure, C-reactive protein, waist-to-hip ratio and lower high-density lipoprotein cholesterol showed non-significant trends with greater eGFR decline in the presence of albuminuria. CONCLUSION: Over a 3 year period, marked eGFR decline was observed with greater baseline albuminuria. Cardiometabolic risk factors were not strong predictors for eGFR decline in Indigenous Australians without albuminuria. Longer follow-up may elucidate the role of these predictors and other mechanisms in chronic kidney disease progression in this population.

JOURNAL ARTICLE

Maniyam MN, Ibrahim AL, Cass AEG, 2018, Decolourization and biodegradation of azo dye methyl red by Rhodococcus strain UCC 0016., Environ Technol, Pages: 1-15, ISSN: 0959-3330

In the present study, locally isolated Rhodococcus strains were attempted as biological tools for methyl red removal, a mutagenic azo dye posing threat to the environment if left untreated. Rhodococcus strain UCC 0016 demonstrated superior methyl red-decolourizing activity of 100% after 24 h at static condition in comparison to Rhodococcus strain UCC 0008 which recorded 65% decolourization after 72 h. Optimization of physicochemical parameters at 30°C, pH 7 and supplementing glucose as the carbon source resulted in improved methyl red-decolourizing activity at static condition and reduced the time taken to achieve complete decolourization by 80%. Higher concentration of methyl red (5 g/L) was able to be decolourized completely within 10 h by adopting the technology of immobilization. The encapsulated cells of Rhodococcus strain UCC 0016 demonstrated higher substrate affinity (Km = 0.6995 g/L) and an accelerated rate of disappearance of methyl red (Vmax = 0.3203 g/L/h) compared to the free cells. Furthermore, the gellan gum beads could be reused up to nine batches without substantial loss in the catalytic activity indicating the economic importance of this protocol. Analysis of methyl red degradation products revealed no germination inhibition on Triticum aestivum and Vigna radiata demonstrating complete toxicity removal of the parent dye after biological treatment. The occurrence of new and altered peaks (UV-Vis and FTIR) further supported the notion that the removal of methyl red by Rhodococcus strain UCC 0016 was indeed through biodegradation. Therefore, this strain has a huge potential as a candidate for efficient bioremediation of wastewater containing methyl red.

JOURNAL ARTICLE

Wang Y, Gallagher M, Li Q, Lo S, Cass A, Finfer S, Myburgh J, Bouman C, Faulhaber-Walter R, Kellum JA, Palevsky PM, Ronco C, Saudan P, Tolwani A, Bellomo Ret al., 2018, Renal replacement therapy intensity for acute kidney injury and recovery to dialysis independence: A systematic review and individual patient data meta-analysis, Nephrology Dialysis Transplantation, Vol: 33, Pages: 1017-1024, ISSN: 0931-0509

© 2017 The Author. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. Background There is no consensus whether higher intensity dose renal replacement therapy (RRT) compared with standard intensity RRT has survival benefit and achieves better renal recovery in acute kidney injury (AKI). Methods In an individual patient data meta-analysis, we merged individual patient data from randomized controlled trials (RCTs) comparing high with standard intensity RRT in intensive care unit patients with severe AKI. The primary outcome was all-cause mortality. The secondary outcome was renal recovery assessed as the proportion of patients who were RRT dependent at key trial endpoints and by time to the end of RRT dependence. Results Of the eight prospective RCTs assessing different RRT intensities, seven contributed individual patient data (n = 3682) to the analysis. Mortality was similar between the two groups at 28 days [769/1884 (40.8%) and 744/1798 (41.4%), respectively; P = 0.40] after randomization. However, more participants assigned to higher intensity therapy remained RRT dependent at the most common key study point of 28 days [e.g. 292/983 (29.7%) versus 235/943 (24.9%); relative risk 1.15 (95% confidence interval 1.00-1.33); P = 0.05]. Time to cessation of RRT through 28 days was longer in patients receiving higher intensity RRT (log-rank test P = 0.02) and when continuous renal replacement therapy was used as the initial modality of RRT (log-rank test P = 0.03). Conclusions In severe AKI patients, higher intensity RRT does not affect mortality but appears to delay renal recovery. Trial Registration Australian New Zealand Clinical Trials Registry (ANZCTR) identifier ACTRN12615000394549 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12615000394549).

JOURNAL ARTICLE

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

JOURNAL ARTICLE

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

JOURNAL ARTICLE

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

JOURNAL ARTICLE

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, 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.

JOURNAL ARTICLE

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

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), HbA1c, 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 eGFR with a follow-up eGFR <60 mL/min/1.73 m2, 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 (-4.22 mL/min/1.73 m2/year [95% CI -7.06 to -1.38]; 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.

JOURNAL ARTICLE

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., Clin Biochem, Vol: 53, Pages: 58-64

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 ≥120ml/min/1.73m2) and albuminuria categories (<3mg/mmol; 3-30mg/mmol; >30mg/mmol). RESULTS: Mean age of the participants was 48years, 64% were female and the median follow-up was 3years. 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 60-90ml/min/1.73m2 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, -4.23) ml/min/1.73m2. CONCLUSION: Short term estimates of kidney function decline can be reliably derived using an easy to implemen

JOURNAL ARTICLE

Weisbord SD, Gallagher M, Jneid H, Garcia S, Cass A, Thwin S-S, 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 PM, PRESERVE Trial Groupet al., 2018, Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine., N Engl J Med, Vol: 378, Pages: 603-614

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 of Veterans Affairs Office of Research and Development and

JOURNAL ARTICLE

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 (Carlton), Vol: 23 Suppl 1, Pages: 5-13

JOURNAL ARTICLE

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 Nephrol, Vol: 19

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 and 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 results are important for informin

JOURNAL ARTICLE

You J, Zhao Y, Lawton P, Guthridge S, McDonald SP, Cass Aet al., 2018, Projecting demands for renal replacement therapy in the Northern Territory: A stochastic Markov model, Australian Health Review, Vol: 42, Pages: 380-386, ISSN: 0156-5788

© 2018 AHHA. Objective The aim of the present study was to evaluate the potential effects of different health intervention strategies on demand for renal replacement therapy (RRT) services in the Northern Territory (NT). Methods A Markov chain simulation model was developed to estimate demand for haemodialysis (HD) and kidney transplantation (Tx) over the next 10 years, based on RRT registry data between 2002 and 2013. Four policy-relevant scenarios were evaluated: (1) increased Tx (2) increased self-care dialysis (3) reduced incidence of end-stage kidney disease (ESKD); and (4) reduced mortality. Results There were 957 new cases of ESKD during the study period, with most patients being Indigenous people (85%). The median age was 50 years at onset and 57 years at death, 12 and 13 years younger respectively than Australian medians. The prevalence of RRT increased 5.6% annually, 20% higher than the national rate (4.7%). If current trends continue (baseline scenario), the demand for facility-based HD (FHD) would approach 100 000 treatments (95% confidence interval 75 000-121 000) in 2023, a 5% annual increase. Increasing Tx (0.3%), increasing self-care (5%) and reducing incidence (5%) each attenuate demand for FHD to ∼70 000 annually by 2023. Conclusions The present study demonstrates the effects of changing service patterns to increase Tx, self-care and prevention, all of which will substantially attenuate the growth in FHD requirements in the NT.

JOURNAL ARTICLE

Grell M, Dincer C, Le T, Lauri A, Nunez Bajo E, Kasimatis M, Barandun G, Maier SA, Cass AEG, Güder Fet al., 2018, Autocatalytic Metallization of Fabrics Using Si Ink, for Biosensors, Batteries and Energy Harvesting, Advanced Functional Materials, ISSN: 1616-301X

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Commercially available metal inks are mainly designed for planar substrates (for example, polyethylene terephthalate foils or ceramics), and they contain hydrophobic polymer binders that fill the pores in fabrics when printed, thus resulting in hydrophobic electrodes. Here, a low-cost binder-free method for the metallization of woven and nonwoven fabrics is presented that preserves the 3D structure and hydrophilicity of the substrate. Metals such as Au, Ag, and Pt are grown autocatalytically, using metal salts, inside the fibrous network of fabrics at room temperature in a two-step process, with a water-based silicon particle ink acting as precursor. Using this method, (patterned) metallized fabrics are being enabled to be produced with low electrical resistance (less than 3.5 Ω sq−1). In addition to fabrics, the method is also compatible with other 3D hydrophilic substrates such as nitrocellulose membranes. The versatility of this method is demonstrated by producing coil antennas for wireless energy harvesting, Ag–Zn batteries for energy storage, electrochemical biosensors for the detection of DNA/proteins, and as a substrate for optical sensing by surface enhanced Raman spectroscopy. In the future, this method of metallization may pave the way for new classes of high-performance devices using low-cost fabrics.

JOURNAL ARTICLE

Lo C, Zimbudzi E, Teede HJ, Kerr PG, Ranasinha S, Cass A, Fulcher G, Gallagher M, Polkinghorne KR, Russell G, Usherwood T, Walker R, Zoungas Set al., 2018, Patient-reported barriers and outcomes associated with poor glycaemic and blood pressure control in co-morbid diabetes and chronic kidney disease, Journal of Diabetes and its Complications, ISSN: 1056-8727

© 2018 Elsevier Inc. Aims: In patients with comorbid diabetes and chronic kidney disease, the extent to which patient-reported barriers to health-care and patient reported outcomes influence the quality of health care is not well established. This study explored the association between patient-reported barriers to health-care, patient activation, quality of life and diabetes self-care, with attainment of glycaemic and blood pressure (BP) targets. Methods: This cross-sectional study recruited adults with diabetes and CKD (eGFR 20 to <60 ml/min/1.73m2) across four hospitals. We combined clinical data with results from a questionnaire comprising measures of patient-identified barriers to care, the Patient Activation Measure (PAM), 12-Item Short Form Survey (SF-12), and the Summary of Diabetes Self-Care Activity (SDSCA). Results: 199 patients, mean age 68.7 (SD 9.6), 70.4% male and 90.0% with type 2 diabetes were studied. Poor glycaemic control was associated with increased odds of patient reported “poor family support” (OR 4.90; 95% CI 1.80 to 13.32, p < 0.002). Poor BP control was associated with increased odds of patient reported, “not having a good primary care physician” (OR 6.01; 2.42 to 14.95, p < 0.001). The number of barriers was not associated with increased odds of poor control (all p > 0.05). Conclusions: Specific patient-reported barriers, lack of patient perceived family and primary care physician support, are associated with increased odds of poor glycaemic and blood pressure control respectively. Interventions addressing these barriers may improve treatment target attainment.

JOURNAL ARTICLE

Kirkham R, Maple-Brown LJ, Freeman N, Beaton B, Lamilami R, Hausin M, Puruntatemeri AM, Wood P, Signal S, Majoni SW, Cass A, Hughes JTet al., 2018, Incorporating indigenous knowledge in health services: a consumer partnership framework, Public Health, ISSN: 0033-3506

© 2018 Objectives: Healthcare policy and planning should be informed by a partnership between healthcare services and healthcare users. This is critical for people who access care frequently such as indigenous Australians who have a high burden of chronic kidney disease. This study aimed to explore the most appropriate ways of enhancing services by incorporating renal patients' expectations and satisfaction of care in Australia's Northern Territory. Study design: This is a participatory action research. Methods: Six aboriginal health users with end-stage kidney disease were recruited to form an Indigenous Reference Group. This group met bimonthly between April and November 2017 and meetings took the same structure as a focus group. Findings from these meetings were presented to health policy and planners in a feedback loop implemented by the study. Results: This framework enabled indigenous knowledge to guide the project, indigenous priorities to be identified in this context and timely feedback of information to inform the strengths and priorities of the health service. Changes were recognised and addressed immediately. Conclusions: This qualitative research framework is a useful mechanism for providing local data to inform patient-centred health system change as expressed by health users. We recommend this consumer partnership framework be embedded into existing operational structures to support the ongoing sustainability of this group.

JOURNAL ARTICLE

Hughes JT, Maple-Brown LJ, Thomas M, Lawton PD, Sinha A, Cass A, Barzi F, Jones G, 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 (Carlton), Vol: 23, Pages: 37-45

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/m2 , WHR 0.94, eGFR 99.2 ml/min/1.73m2 ). 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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