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
to

439 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

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

Barr ELM, Barzi F, Hughes JT, Jerums G, O'Dea K, Brown ADH, Ekinci EI, Jones GRD, 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, Vol: 23, Pages: 682-689, ISSN: 1320-5358

© 2017 Asian Pacific Society of Nephrology 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 A1cand 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

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

Bollella P, Sharma S, Cass AEG, Antiochia Ret al., 2018, Microneedle-based biosensor for minimally-invasive lactate detection., Biosens Bioelectron

Here we report the first mediated microneedles-based biosensor for minimally invasive continuous sensing of lactate in the dermal interstitial fluid (ISF). To further demonstrate the capability of microneedle arrays as second generation biosensors we have functionalized gold microneedles with nanocarbons at which mediated electron transfer of lactate oxidase takes place. In particular the gold surface of the microneedles electrode has been modified in 3 subsequent steps: i) electrodeposition of Au-multiwalled carbon nanotubes (MWCNTs); ii) electropolymerization of the mediator, methylene blue (MB); iii) immobilization of the enzyme lactate oxidase (LOX) by drop-casting procedure. The resulting microneedle-based LOX biosensor displays an interference-free lactate detection without compromising its sensitivity, stability, selectivity and response time. The performance of the microneedle array, second generation biosensor for lactate detection was assessed in artificial interstitial fluid and in human serum, both spiked with lactate. The results reveal that the new microneedles lactate sensor holds interesting promise for the development of a real-time monitoring device to be used in sport medicine and clinical care.

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, Vol: 23, Pages: 5-13, ISSN: 1320-5358

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.

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

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

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

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 of Systematic Reviews, Vol: 2018

© 2018 The Cochrane Collaboration. 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-

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

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

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

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.

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

Piletsky SS, Cass AEG, Piletska EV, Czulak J, Piletsky SAet al., 2018, A Novel Assay Format as an Alternative to ELISA: MINA Test for Biotin, ChemNanoMat

© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim A novel abiotic assay based on biotin-specific fluorescent molecularly imprinted polymer nanoparticles (nanoMIPs) which acted as both reporter probes and binding agents, was developed. This is a first report of an assay which, unlike ELISA, required no washing steps or addition of enzyme substrates, making it more user-friendly. The components of the molecularly imprinted polymer nanoparticles assay (MINA) were assembled in microtiter plates fitted with magnetic inserts. The fluorescent nanoMIPs were bound to biotin-conjugated magnetic particles, which were attracted to the inserts. The addition of free biotin caused a displacement of the fluorescent nanoMIPs into solution, generating a signal proportional to the concentration of biotin. The nanoMIPs had a dissociation constant (Kd) of 14 nM, allowing the assay to detect biotin at nano-molar concentrations. The pre-assembled assay only required the addition of the sample and measurement of the fluorescence, and it functioned well after six weeks of storage without refrigeration. The assay did not show the susceptibility to several compounds which are known to interfere with avidin and streptavidin-based assays, such as mercaptoethanol and sugars. The protocols optimized in this work could be used to develop the abiotic assays for any other compound of interest.

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

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

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

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

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.

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

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

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

Angell B, Laba T-L, 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., Int J Equity Health, Vol: 16

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 t

JOURNAL ARTICLE

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., Clin Biochem, Vol: 50, Pages: 301-308

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 4h. 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 (15.0mL/min/1.73m2; 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.

JOURNAL ARTICLE

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

JOURNAL ARTICLE

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

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 transplantation were described but

JOURNAL ARTICLE

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 Serv Res, Vol: 17

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 broader 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 and qualitative data that wil

JOURNAL ARTICLE

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 P, HERO Study Collaborative Groupet 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 (Carlton), Vol: 22, Pages: 548-554

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 biologi

JOURNAL ARTICLE

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