Developing an integrated clinical decision support system for the early identification and management of kidney disease-building cross-sectoral partnerships.

BACKGROUND: The burden of chronic conditions is growing in Australia with people in remote areas experiencing high rates of disease, especially kidney disease. Health care in remote areas of the Northern Territory (NT) is complicated by a mobile population, high staff turnover, poor communication between health services and complex comorbid health conditions requiring multidisciplinary care. AIM: This paper aims to describe the collaborative process between research, government and non-government health services to develop an integrated clinical decision support system to improve patient care. METHODS: Building on established partnerships in the government and Aboriginal Community-Controlled Health Service (ACCHS) sectors, we developed a novel digital clinical decision support system for people at risk of developing kidney disease (due to hypertension, diabetes, cardiovascular disease) or with kidney disease. A cross-organisational and multidisciplinary Steering Committee has overseen the design, development and implementation stages. Further, the system's design and functionality were strongly informed by experts (Clinical Reference Group and Technical Working Group), health service providers, and end-user feedback through a formative evaluation. RESULTS: We established data sharing agreements with 11 ACCHS to link patient level data with 56 government primary health services and six hospitals. Electronic Health Record (EHR) data, based on agreed criteria, is automatically and securely transferred from 15 existing EHR platforms. Through clinician-determined algorithms, the system assists clinicians to diagnose, monitor and provide guideline-based care for individuals, as well as service-level risk stratification and alerts for clinically significant events. CONCLUSION: Disconnected health services and separate EHRs result in information gaps and a health and safety risk, particularly for patients who access multiple health services. However, barriers to clinical data sharing between health services still exist. In this first phase, we report how robust partnerships and effective governance processes can overcome these barriers to support clinical decision making and contribute to holistic care.

Socio-environmental and clinical features of invasive group A streptococcal disease in the Northern Territory of Australia.

Objective: To describe the socio-environmental profile and clinical features of invasive group A streptococcal (iGAS) infections in the Northern Territory (NT) of Australia over 10 years. Methods: Cases of iGAS disease diagnosed between 1 May 2011 and 30 April 2021 were retrospectively identified from the NT Notifiable Diseases System and electronic health records accessed. Remoteness of residence, socio-economic index, seasonality and clinical characteristics were recorded. Results: There were 692 cases of iGAS disease identified in the NT during the period 1 May 2011 - 30 April 2021. The age-standardised incidence of iGAS disease was significantly higher in people living in very remote (57.1 cases per 100,000 population, 95% confidence interval [95% CI]: 48.6-65.5) and remote areas (40.9 cases per 100,000 population, 95% CI: 34.7-47.2) than in outer regional areas of the NT (15.7 cases per 100,000 population, 95% CI: 13.4-17.9). People with socio-economic disadvantage were also disproportionately affected, with an incidence of 52.6 cases per 100,000 population (95% CI: 46.2-58.9) in decile 1-3 populations, compared to 8.9 cases per 100,000 population (95% CI: 6.9-10.9) for decile 7-10. For cases with recorded severity data, 135 of 378 (36%) met locally-defined criteria for severe iGAS disease. Recurrent iGAS disease was commonly observed in the dialysis cohort, affecting 17 of the 106 patients during the study period (16% recurrence rate) and causing two deaths. Five molecularly-confirmed clusters of iGAS disease were identified from the study period. Conclusions: iGAS disease is unevenly affecting people in the NT. Those living in areas of socio-economic disadvantage, those in remote and very remote communities, and those receiving dialysis were most affected. It is important that primordial, primary and secondary prevention measures be directed towards supporting these disadvantaged population groups.

Comparison of two ferritin assay platforms to assess their level of agreement in measuring serum and plasma ferritin levels in patients with chronic kidney disease.

BACKGROUND: Ferritin levels are used to make decisions on therapy of iron deficiency in patients with chronic kidney disease (CKD). Hyperferritinaemia, common among patients with CKD from the Northern Territory (NT) of Australia, makes use of ferritin levels as per clinical guidelines challenging. No gold standard assay exists for measuring ferritin levels. Significant variability between results from different assays creates challenges for clinical decision-making regarding iron therapy. In the NT, different laboratories use different methods. In 2018, Territory Pathology changed the assay from Abbott ARCHITECT i1000 (AA) to Ortho-Clinical Diagnostics Vitros 7600 (OCD). This was during the planning of the INtravenous iron polymaltose for First Nations Australian patients with high FERRitin levels on haemodialysis (INFERR) clinical trial. The trial design was based on AA assay ferritin levels. We compared the two assays' level of agreement in measuring ferritin levels in CKD patients. METHODS: Samples from INFERR clinical trial participants were analysed. Other samples from patients whose testing were completed the same day on OCD analyzers and run within 24 h on AA analyzers were added to ensure wide range of ferritin levels, adding statistical strength to the comparison. Ferritin levels from both assays were compared using Pearson's correlation, Bland-Altman, Deming and Passing-Bablok regression analyses. Differences between sample types, plasma and serum were assessed. RESULTS: Sixty-eight and 111 (179) samples from different patients from Central Australia and Top End of Australia, respectively, were analyzed separately and in combination. The ferritin levels ranged from 3.1 µg/L to 3354 µg/L and 3 µg/L to 2170 µg/L for AA and OCD assays respectively. Using Bland-Altman, Deming and Passing-Bablok regression methods for comparison, ferritin results were consistently 36% to 44% higher with AA than OCD assays. The bias was up to 49%. AA ferritin results were the same in serum and plasma. However, OCD ferritin results were 5% higher in serum than plasma. CONCLUSIONS: When making clinical decisions, using ferritin results from the same assay in patients with CKD is critical. If the assay is changed, it is essential to assess agreement between results from the new and old assays. Further studies to harmonize ferritin assays are required.

Benefit and harm of anticoagulation in the prevention of thromboembolic stroke for non-valvular atrial fibrillation in haemodialysis patients: a Top End of Northern Australia study.

BACKGROUND: Warfarin for the prevention of non-valvular atrial fibrillation (AF)-related thromboembolic stroke in patients on maintenance haemodialysis is controversial. Despite the exclusion of haemodialysis patients in randomised control trials, the American Heart Association/American College of Cardiology has recommended warfarin in high-risk AF patients. AIMS: To retrospectively examine the utility of warfarin anticoagulation therapy in our prevalent haemodialysis patients over 10 years of follow up. METHODS: Eligible patients were retrospectively identified and stratified to two cohorts based on whether warfarin was prescribed. The outcomes of interest were ischaemic stroke, haemorrhagic stroke and death from any cause. Rate ratio and Cox proportional hazard regression model were used to compare the differences in outcome between the two cohorts. The Kaplan-Meier method was used to analyse survival. RESULTS: Three ischaemic strokes and four haemorrhagic strokes occurred in the unexposed group of 166 patients over 484.44 patient-years of follow up. One ischaemic stroke and no cases of haemorrhagic stroke occurred in the exposed warfarin group of 16 patients over 39.32 patient-years of follow up. Eighty-seven percent of patients in both groups were indigenous. More than 90% of each cohort had a CHA2DS2-VaSc score ≥2. One hundred and one deaths, 90 in the unexposed group and 11 in the warfarin group, occurred in the follow-up period. A non-statistically significant trend towards increasing mortality was observed in the warfarin group (hazard ratio = 1.63; P = 0.13). CONCLUSION: This retrospective study of prevalent haemodialysis patients with co-existing history of non-valvular AF failed to demonstrate sufficient evidence for the routine use of warfarin for prophylaxis of thromboembolic stroke.

Important lack of difference in tacrolimus and mycophenolic acid pharmacokinetics between Aboriginal and Caucasian kidney transplant recipients.

AIM: To examine whether differences in tacrolimus and mycophenolic acid (MPA) pharmacokinetics contribute to the poorer kidney transplant outcomes experienced by Aboriginal Australians. METHODS: Concentration-time profiles for tacrolimus and MPA were prospectively collected from 43 kidney transplant recipients: 27 Aboriginal and 16 Caucasian. Apparent clearance (CL/F) and distribution volume (V/F) for each individual were derived from concentration-time profiles combined with population pharmacokinetic priors, with subsequent assessment for between-group difference in pharmacokinetics. In addition, population pharmacokinetic models were developed using the prospective dataset supplemented by previously developed structural models for tacrolimus and MPA. The change in NONMEM objective function was used to assess improvement in goodness of model fit. RESULTS: No differences were found between Aboriginal and Caucasian groups or empirical Bayes estimates, for CL/F or V/F of MPA or tacrolimus. However, a higher prevalence of CYP3A5 expressers (26% compared with 0%) and wider between-subject variability in tacrolimus CL/F (SD = 5.00 compared with 3.25 L/h/70 kg) were observed in the Aboriginal group, though these differences failed to reach statistical significance (p = .07 and p = .08). CONCLUSION: There were no differences in typical tacrolimus or MPA pharmacokinetics between Aboriginal and Caucasian kidney transplant recipients. This means that Bayesian dosing tools developed to optimise tacrolimus and MPA dosing in Caucasian recipients may be applied to Aboriginal recipients. In turn, this may improve drug exposure and thereby transplant outcomes in this group. Aboriginal recipients appeared to have greater between-subject variability in tacrolimus CL/F and a higher prevalence of CYP3A5 expressers, attributes that have been linked with inferior outcomes.

INFERR-Iron infusion in haemodialysis study: INtravenous iron polymaltose for First Nations Australian patients with high FERRitin levels on haemodialysis-a protocol for a prospective open-label blinded endpoint randomised controlled trial.

BACKGROUND: The effectiveness of erythropoiesis-stimulating agents, which are the main stay of managing anaemia of chronic kidney disease (CKD), is largely dependent on adequate body iron stores. The iron stores are determined by the levels of serum ferritin concentration and transferrin saturation. These two surrogate markers of iron stores are used to guide iron replacement therapy. Most Aboriginal and/or Torres Islander Australians of the Northern Territory (herein respectfully referred to as First Nations Australians) with end-stage kidney disease have ferritin levels higher than current guideline recommendations for iron therapy. There is no clear evidence to guide safe and effective treatment with iron in these patients. We aim to assess the impact of intravenous iron treatment on all-cause death and hospitalisation with a principal diagnosis of all-cause infection in First Nations patients on haemodialysis with anaemia, high ferritin levels and low transferrin saturation METHODS: In a prospective open-label blinded endpoint randomised controlled trial, a total of 576 participants on maintenance haemodialysis with high ferritin (> 700 µg/L and ≤ 2000 µg/L) and low transferrin saturation (< 40%) from all the 7 renal units across the Northern Territory of Australia will be randomised 1:1 to receive intravenous iron polymaltose 400 mg once monthly (200 mg during 2 consecutive haemodialysis sessions) (Arm A) or no IV iron treatment (standard treatment) (Arm B). Rescue therapy will be administered when the ferritin levels fall below 700 µg/L or when clinically indicated. The primary outcome will be the differences between the two study arms in the risk of hospitalisation with all-cause infection or death. An economic analysis and several secondary and tertiary outcomes analyses will also be performed. DISCUSSION: The INFERR clinical trial will address significant uncertainty on the safety and efficacy of iron therapy in First Nations Australians with CKD with hyperferritinaemia and evidence of iron deficiency. This will hopefully lead to the development of evidence-based guidelines. It will also provide the opportunity to explore the causes of hyperferritinaemia in First Nations Australians from the Northern Territory. TRIAL REGISTRATION: This trial is registered with The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12620000705987 . Registered 29 June 2020.

"The talking bit of medicine, that's the most important bit": doctors and Aboriginal interpreters collaborate to transform culturally competent hospital care.

BACKGROUND: In hospitals globally, patient centred communication is difficult to practice, and interpreters are underused. Low uptake of interpreters is commonly attributed to limited interpreter availability, time constraints and that interpreter-medicated communication in healthcare is an aberration. In Australia's Northern Territory at Royal Darwin Hospital, it is estimated around 50% of Aboriginal patients would benefit from an interpreter, yet approximately 17% get access. Recognising this contributes to a culturally unsafe system, Royal Darwin Hospital and the NT Aboriginal Interpreter Service embedded interpreters in a renal team during medical ward rounds for 4 weeks in 2019. This paper explores the attitudinal and behavioural changes that occurred amongst non-Indigenous doctors and Aboriginal language interpreters during the pilot. METHODS: This pilot was part of a larger Participatory Action Research study examining strategies to achieve culturally safe communication at Royal Darwin Hospital. Two Yolŋu and two Tiwi language interpreters were embedded in a team of renal doctors. Data sources included interviews with doctors, interpreters, and an interpreter trainer; reflective journals by doctors; and researcher field notes. Inductive thematic analysis, guided by critical theory, was conducted. RESULTS: Before the pilot, frustrated doctors unable to communicate effectively with Aboriginal language speaking patients acknowledged their personal limitations and criticised hospital systems that prioritized perceived efficiency over interpreter access. During the pilot, knowledge of Aboriginal cultures improved and doctors adapted their work routines including lengthening the duration of bed side consults. Furthermore, attitudes towards culturally safe communication in the hospital changed: doctors recognised the limitations of clinically focussed communication and began prioritising patient needs and interpreters who previously felt unwelcome within the hospital reported feeling valued as skilled professionals. Despite these benefits, resistance to interpreter use remained amongst some members of the multi-disciplinary team. CONCLUSIONS: Embedding Aboriginal interpreters in a hospital renal team which services predominantly Aboriginal peoples resulted in the delivery of culturally competent care. By working with interpreters, non-Indigenous doctors were prompted to reflect on their attitudes which deepened their critical consciousness resulting in behaviour change. Scale up of learnings from this pilot to broader implementation in the health service is the current focus of ongoing implementation research.

From "stuck" to satisfied: Aboriginal people's experience of culturally safe care with interpreters in a Northern Territory hospital.

BACKGROUND: Globally, interpreters are underused by health providers in hospitals, despite 40 years of evidence documenting benefits to both patients and providers. At Royal Darwin Hospital, in Australia's Northern Territory, 60-90% of patients are Aboriginal, and 60% speak an Aboriginal language, but only approximately 17% access an interpreter. Recognising this system failure, the NT Aboriginal Interpreter Service and Royal Darwin Hospital piloted a new model with interpreters embedded in a renal team during medical ward rounds for 4 weeks in 2019. METHODS: This research was embedded in a larger Participatory Action Research study examining cultural safety and communication at Royal Darwin Hospital. Six Aboriginal language speaking patients (five Yolŋu and one Tiwi), three non-Indigenous doctors and five Aboriginal interpreter staff were purposefully sampled. Data sources included participant interviews conducted in either the patient's language or English, researcher field notes from shadowing doctors, doctors' reflective journals, interpreter job logs and patient language lists. Inductive narrative analysis, guided by critical theory and Aboriginal knowledges, was conducted. RESULTS: The hospital experience of Yolŋu and Tiwi participants was transformed through consistent access to interpreters who enabled patients to express their clinical and non-clinical needs. Aboriginal language-speaking patients experienced a transformation to culturally safe care. After initially reporting feeling "stuck" and disempowered when forced to communicate in English, participants reported feeling satisfied with their care and empowered by consistent access to the trusted interpreters, who shared their culture and worldviews. Interpreters also enabled providers to listen to concerns and priorities expressed by patients, which resulted in holistic care to address social determinants of health. This improved patient trajectories and reduced self-discharge rates. CONCLUSIONS: A culturally unsafe system which restricted people's ability to receive equitable healthcare in their first language was overturned by embedding interpreters in a renal medical team. This research is the first to demonstrate the importance of consistent interpreter use for providing culturally safe care for Aboriginal patients in Australia.

Narrative Review of Hyperferritinemia, Iron Deficiency, and the Challenges of Managing Anemia in Aboriginal and Torres Strait Islander Australians With CKD.

Aboriginal and Torres Strait Islander Australians (Indigenous Australians) suffer some of the highest rates of chronic kidney disease (CKD) in the world. Among Indigenous Australians in remote areas of the Northern Territory, prevalence rates for renal replacement therapy (RRT) are up to 30 times higher than national prevalence. Anemia among patients with CKD is a common complication. Iron deficiency is one of the major causes. Iron deficiency is also one of the key causes of poor response to the mainstay of anemia therapy with erythropoiesis-stimulating agents (ESAs). Therefore, the effective management of anemia in people with CKD is largely dependent on effective identification and correction of iron deficiency. The current identification of iron deficiency in routine clinical practice is dependent on 2 surrogate markers of iron status: serum ferritin concentration and transferrin saturation (TSAT). However, questions exist regarding the use of serum ferritin concentration in people with CKD because it is an acute-phase reactant that can be raised in the context of acute and chronic inflammation. Serum ferritin concentration among Indigenous Australians receiving RRT is often markedly elevated and falls outside reference ranges within most national and international guidelines for iron therapy for people with CKD. This review explores published data on the challenges of managing anemia in Indigenous people with CKD and the need for future research on the efficacy and safety of treatment of anemia of CKD in patients with high ferritin and evidence iron deficiency.

Baseline liver function tests and full blood count indices and their association with progression of chronic kidney disease and renal outcomes in Aboriginal and Torres Strait Islander people: the eGFR follow- up study.

BACKGROUND: Determination of risks for chronic kidney disease (CKD) progression could improve strategies to reduce progression to ESKD. The eGFR Study recruited a cohort of adult Aboriginal and Torres Strait Islander people (Indigenous Australians) from Northern Queensland, Northern Territory and Western Australia, aiming to address the heavy CKD burden experienced within these communities. METHODS: Using data from the eGFR study, we explored the association of baseline liver function tests (LFTs) (alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin and albumin) and full blood count (FBC) indices (white blood cell and red blood cell counts and haemoglobin) with annual eGFR decline and renal outcomes (first of 30% decline in eGFR with a follow-up eGFR < 60 mL/min/1.73 m2, initiation of renal replacement therapy, or renal death). Comparisons of baseline variables across eGFR categories were calculated using analysis of variance and logistic regression as appropriate. Linear and multivariable regression models were used to estimate the annual change in eGFR for changes in FBC indices and LFTs. Cox proportional hazard models were used to estimate the hazard ratio for developing renal outcome for changes in baseline FBC indices and LFTs. RESULTS: Of 547 participants, 540 had at least one baseline measure of LFTs and FBC indices. The mean age was 46.1 (14.7) years and 63.6% were female. The median follow-up was 3.1 (IQR 2.8-3.6) years. Annual decline in eGFR was associated with low serum albumin (p < 0.001) and haemoglobin (p = 0.007). After adjustment for age, gender, urine albumin/creatinine ratio, diabetes, BMI, CRP, WHR, alcohol consumption, cholesterol and triglycerides, low serum albumin (p < 0.001), haemoglobin (p = 0.012) and bilirubin (p = 0.011) were associated with annual decline in eGFR. Renal outcomes were inversely associated with serum albumin (p < 0.001), bilirubin (p = 0.012) and haemoglobin (p < 0.001) and directly with GGT (p = 0.007) and ALP (p < 0.001). Other FBC indices and LFTs were not associated with annual decline in eGFR or renal outcomes. CONCLUSIONS: GGT, ALP, bilirubin, albumin and haemoglobin independently associate with renal outcomes. Contrary to findings from other studies, no association was found between renal outcomes and other FBC indices. These findings may help focus strategies to prevent disease progression in this high-risk population.

Weight change trajectories in Aboriginal and Torres Strait islander Australians after kidney transplantation: a cohort analysis using the Australia and New Zealand Dialysis and Transplant registry (ANZDATA).

BACKGROUND: Weight change post-kidney transplantation and its associations in Aboriginal and Torres Strait Islander Australians, a group known to have poor patient and graft outcomes, are unknown. Weight change based on body mass index in Aboriginal and Torres Strait Islander Australian recipients was compared to non- indigenous recipients. METHODS: We performed a cohort analysis of data from the Australia and New Zealand Dialysis and Transplant Registry for first deceased donor kidney transplant recipients between 1995 and 2014 in Australia. Weight change post-kidney transplantation was analysed by recipient ethnicity using multivariate mixed effect linear regression analysis. RESULTS: There were 343 (5.24%) Aboriginal and Torres Strait Islander Australian kidney transplants recipients from a total of 6550 recipients. They had higher pre-transplant BMI (p < 0.001), higher rates of current smokers (p < 0.001), diabetes (p < 0.001), coronary artery disease (p < 0.001), cerebrovascular disease (p = 0.011) and peripheral vascular disease (p = 0.013), ≥4 HLA mismatches (p < 0.001), graft loss (p < 0.001), mortality (p < 0.001) and rejection rates (p < 0.001). Weight increased in the first 2 years post-transplantation in both Aboriginal and Torres Strait Islander Australians and non-indigenous Australians. After adjusting for the baseline differences, weight change diverged significantly at 6, 12 and 24 months. The difference was most marked between 6 and 12 months. When stratified by pre-transplantation BMI, all groups except underweight reflected this pattern. Normal weight and obese Aboriginal and Torres Strait Islander Australian recipients had substantial increase at 12 and 24 months and overweight at 6, 12 and 24 months. The difference in BMI trajectories between Aboriginal and Torres Strait Islander Australians and non- indigenous Australian transplant recipients persisted after adjustment in multivariate mixed effect linear regression analysis. CONCLUSIONS: Post-kidney transplantation weight gain in this high-risk population is substantial and greater than in non-indigenous Australians. Further studies should assess the effect of treatment factors and weight gain on transplant and recipient outcomes.

Adherence to Treatment Guidelines in Heart Failure Patients in the Top End Region of Northern Territory.

BACKGROUND: Heart failure (HF) is associated with significant morbidity and mortality and recurrent hospitalisations, particularly in the Indigenous Australians of the Northern Territory. In remote Northern Australia, the epidemiology is less clear but anecdotal evidence suggests it may be worse. In addition, some anecdotal evidence suggests that prognostic pharmacological therapy could also be underutilised. Minimal HF data exists in the remote and Indigenous settings, making this study unique. METHODS: A retrospective cohort review of pharmacological management of 99 patients from 1 January 2014 to 31 December 2014 was performed. RESULTS: Ninety-nine (99) patients were identified. 59.6% were non-Indigenous vs 40.4% Indigenous. The majority was male (69.7%). Indigenous patients were younger; median age was 51.4 (43.4-60.6) vs 70.5 (62.2-77.0), p<0.001. Major causes of HF were coronary artery disease (61%) and dilated cardiomyopathy (27%). Associated comorbidities included hypertension (52%), dyslipidaemia (38%), diabetes mellitus (40%) and atrial fibrillation (25%). The use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) and ß-blocker was 68% and 87%, respectively. Forty-one (41) patients not on an ACEI/ARB and/or ß-blocker were identified. Seventeen (17) of those patients (42%) did not receive an ACEI/ARB because of renal failure. Four (4) patients (10%) did not take a ß-blocker due to hypotension. Fourteen (14) patients (34%) were not prescribed an ACEI/ARB and/or ß-blocker had no identifiable contraindications. CONCLUSIONS: Indigenous patients are over-represented at a younger age demonstrating the alarming rate of disease burden in NT's young Indigenous population. Generally, ACEI/ARBs were underutilised compared to ß-blockers with renal impairment being the primary contraindication. There is a need to develop processes to further improve the use of heart failure medications and setting up a HF database could be the first step in progress.

Magnesium and Human Health: Perspectives and Research Directions.

Magnesium is the fourth most abundant cation in the body. It has several functions in the human body including its role as a cofactor for more than 300 enzymatic reactions. Several studies have shown that hypomagnesemia is a common electrolyte derangement in clinical setting especially in patients admitted to intensive care unit where it has been found to be associated with increase mortality and hospital stay. Hypomagnesemia can be caused by a wide range of inherited and acquired diseases. It can also be a side effect of several medications. Many studies have reported that reduced levels of magnesium are associated with a wide range of chronic diseases. Magnesium can play important therapeutic and preventive role in several conditions such as diabetes, osteoporosis, bronchial asthma, preeclampsia, migraine, and cardiovascular diseases. This review is aimed at comprehensively collating the current available published evidence and clinical correlates of magnesium disorders.

Trimethoprim+Sulfamethoxazole Reduces Rates of Melioidosis in High-Risk Hemodialysis Patients.

INTRODUCTION: Melioidosis causes sepsis and death in the Top End of Northern Australia during the monsoonal wet season. Dialysis-dependent adults suffer higher melioidosis rates compared to low rates among renal transplant patients who routinely receive trimethoprim+sulfamethoxazole prophylaxis. METHODS: We performed a prospective interventional study to determine the efficacy and safety of daily trimethoprim+sulfamethoxazole prophylaxis in hemodialysis patients during the wet season, from 1 November 2014 to 30 April 2015. Hemodialysis (for ≥ 3 months) patients ≥ 18 years of age were offered treatment. A total of 269 patients on hemodialysis were eligible. Eight of the 269 patients (3%) were excluded from the analysis for being on melioidosis treatment. In all, 169 of 261 patients (64.8%) received the prophylaxis, and 92 of 261 patients (35.2%) did not, because of allergy history (n = 10), remoteness and logistical reasons (n = 60), poor dialysis attendance (n = 11), and refusal (n = 11). We monitored for clinical side effects 3 times weekly and neutropenia, thrombocytopenia, and liver function monthly throughout treatment and for 2 months posttreatment. RESULTS: In all, 169 of 261 patients (64.8%) received the prophylaxis. There was no age (years) difference by group (prophylaxis vs. nonprophylaxis, 54.7 [11.3] vs. 54.3 [11.2] [P = 0.751]). Sixteen of 261 patients (6%) had melioidosis. The event frequency was 0% (0/169, prophylaxis, vs. 17.4% [16/92, nonprophylaxis], P < 0.001). Higher thrombocytopenia and neutropenia rates were noted in the prophylaxis group. These did not warrant treatment stoppage. There was no difference in liver function. Three patients (1.8%) withdrew from the treatment because of side effects. CONCLUSION: Daily dosing was effective and safe. Posthemodialysis dosing in the subsequent seasons was effective and safer. We recommend this approach in melioidosis-prevalent regions.

Economic and quality of care evaluation of dialysis service models in remote Australia: protocol for a mixed methods study.

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 will investigate health costs less directly related to dialysis treatment, costs to government such as housing and/or education and the health, social and economic outcomes experienced by patients. This approach fills an evidence gap critical to health service planners.

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.

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 (r2 = 0.11, p < 0.001), no correlation between ferritin and CRP (r2 = 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.

Analysis of clinical presentation, pathological spectra, treatment and outcomes of biopsy-proven acute postinfectious glomerulonephritis in adult indigenous people of the Northern Territory of Australia.

AIM: Acute postinfectious glomerulonephritis is common in indigenous communities in the Northern Territory, Australia. It is a major risk factor for the high prevalence of chronic kidney disease. We aimed to analyse the clinical presentation, pathological spectra, treatment and outcomes of biopsy-proven acute postinfectious glomerulonephritis in the Northern Territory. METHODS: We performed a retrospective cohort analysis of all adult patients (≥18 years) who were diagnosed with acute postinfectious glomerulonephritis on native renal biopsies from 01/01/2004 to 31/05/2014. The outcome measure was end-stage renal disease requiring long-term dialysis. RESULTS: Forty-three of 340 patients who had renal biopsies had acute postinfectious glomerulonephritis. Most were Aboriginals (88.4%). They had co-morbidities; diabetes mellitus (60.5%), hypertension (60.5%) and smoking (56.4%). Forty-nine per cent had multiple pathologies on biopsy. Predominant histological pattern was diffuse proliferative glomerulonephritis (72%). Main sites of infections were skin (47.6%) and upper respiratory tract infection (26.2%) with streptococcus and staphylococcus as predominant organisms. Fifty per cent of patients developed end-stage renal disease. On multivariable logistic regression analysis, those on dialysis had higher baseline creatinine (P = 0.003), higher albumin/creatinine ratio at presentation (P = 0.023), higher serum creatinine at presentation (P = 0.02) and lower estimated glomerular filtration rate at presentation (P = 0.012). CONCLUSION: Overall, most patients had pre-existing pathology with superimposed acute postinfectious glomerulonephritis that led to poor outcomes in our cohort.