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.

Hospital admission rates and related outcomes among adult Aboriginal australians with bronchiectasis - a ten-year retrospective cohort study.

BACKGROUND: This study assessed hospitalisation frequency and related clinical outcomes among adult Aboriginal Australians with bronchiectasis over a ten-year study period. METHOD: This retrospective study included patients aged ≥ 18 years diagnosed with bronchiectasis between 2011 and 2020 in the Top End, Northern Territory of Australia. Hospital admissions restricted to respiratory conditions (International Classification of Diseases (ICD) code J) and relevant clinical parameters were assessed and compared between those with and without hospital admissions. RESULTS: Of the 459 patients diagnosed to have bronchiectasis, 398 (87%) recorded at least one respiratory related (ICD-J code) hospitalisation during the 10-year window. In comparison to patients with a recorded hospitalisation against those without-hospitalised patients were older (median 57 vs 53 years), predominantly females (54 vs 46%), had lower body mass index (23 vs 26 kg/m2) and had greater concurrent presence of chronic obstructive pulmonary disease (COPD) (88 vs 47%), including demonstrating lower spirometry values (forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) (median FVC 49 vs 63% & FEV1 36 vs 55% respectively)). The total hospitalisations accounted for 3,123 admissions (median 4 per patient (IQR 2, 10)), at a median rate of 1 /year (IQR 0.5, 2.2) with a median length of 3 days (IQR 1, 6). Bronchiectasis along with COPD with lower respiratory tract infection (ICD code-J44) was the most common primary diagnosis code, accounting for 56% of presentations and 46% of days in hospital, which was also higher for patients using inhaled corticosteroids (81 vs 52%, p = 0.007). A total of 114 (29%) patients were recorded to have had an ICU admission, with a higher rate, including longer hospital stay among those patients with bronchiectasis and respiratory failure related presentations (32/35, 91%). In multivariate regression model, concurrent presence of COPD or asthma alongside bronchiectasis was associated with shorter times between subsequent hospitalisations (-423 days, p = 0.007 & -119 days, p = 0.02 respectively). CONCLUSION: Hospitalisation rates among adult Aboriginal Australians with bronchiectasis are high. Future interventions are required to explore avenues to reduce the overall morbidity associated with bronchiectasis among Aboriginal Australians.

Bronchiectasis among Indigenous adults in the Top End of the Northern Territory, 2011-2020: a retrospective cohort study.

OBJECTIVES: To assess the prevalence of bronchiectasis among Aboriginal and Torres Strait Islander (Indigenous) adults in the Top End of the Northern Territory, and mortality among Indigenous adults with bronchiectasis. STUDY DESIGN: Retrospective cohort study. SETTING, PARTICIPANTS: Aboriginal and Torres Strait Islander adults (18 years or older) living in the Top End Health Service region of the NT in whom bronchiectasis was confirmed by chest computed tomography (CT) during 1 January 2011 - 31 December 2020. MAIN OUTCOME MEASURES: Prevalence of bronchiectasis, and all-cause mortality among Indigenous adults with CT-confirmed bronchiectasis - overall, by sex, and by health district - based on 2011 population numbers (census data). RESULTS: A total of 23 722 Indigenous adults lived in the Top End Health Service region in 2011; during 2011-2020, 459 people received chest CT-confirmed diagnoses of bronchiectasis. Their median age was 47.5 years (interquartile range [IQR], 39.9-56.8 years), 254 were women (55.3%), and 425 lived in areas classified as remote (93.0%). The estimated prevalence of bronchiectasis was 19.4 per 1000 residents (20.6 per 1000 women; 18.0 per 1000 men). The age-adjusted prevalence of bronchiectasis was 5.0 (95% CI, 1.4-8.5) cases per 1000 people in the Darwin Urban health area, and 18-36 cases per 1000 people in the three non-urban health areas. By 30 April 2023, 195 people with bronchiectasis had died (42.5%), at a median age of 60.3 years (IQR, 50.3-68.9 years). CONCLUSION: The prevalence of bronchiectasis burden among Indigenous adults in the Top End of the NT is high, but differed by health district, as is all-cause mortality among adults with bronchiectasis. The socio-demographic and other factors that contribute to the high prevalence of bronchiectasis among Indigenous Australians should be investigated so that interventions for reducing its burden can be developed.

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.

Exploring the appropriateness of prescribing practice of inhaled pharmacotherapy among Aboriginal Australians in the Top End Northern Territory of Australia: a retrospective cohort study.

BACKGROUND: Aboriginal Australians are reported to have a high burden of chronic airway diseases. However, prescribing patterns and related outcomes of airway directed inhaled pharmacotherapy, (short-acting beta agonists (SABA), short-acting muscarinic antagonists (SAMA), long-acting ß-agonists (LABA), long-acting muscarinic antagonists (LAMA) and inhaled corticosteroids (ICS)) among Aboriginal Australian patients with chronic airway disease have been sparsely reported in the past. METHODS: A retrospective cohort study was conducted, using clinical, spirometry data, chest radiology, primary healthcare (PHC) presentations and hospital admission rates among Aboriginal patients identified to have been prescribed inhaled pharmacotherapy in remote and rural communities referred to the respiratory specialist service in the Top End, Northern Territory of Australia. RESULTS: Of the 372 identified active patients, 346 (93%) had inhaled pharmacotherapy prescribed (64% female, median age 57.7 years). ICS was the most common prescription (72% of the total cohort) and was recorded to be prescribed in 76% of patients with bronchiectasis, and 80% of patients with asthma or chronic obstructive pulmonary disease (COPD). Fifty-eight percent of patients had a respiratory hospital admission and 57% had a recorded PHC presentation for a respiratory issue during the study period, with a higher rate of hospital admissions among patients prescribed ICS compared with those on SAMA/SABA or LAMA/LABA without ICS (median rate (per person per year) 0.42 vs 0.21 and 0.21 (p=0.004). Regression models demonstrated that presence of COPD or bronchiectasis alongside ICS was associated with significantly increased hospitalisation rates (1.01 admissions/person/year (95% CI 0.15 to 1.87) and 0.71 admissions/person/year (95% CI 0.23 to 1.18) against patients without COPD/bronchiectasis, respectively). CONCLUSIONS: This study demonstrates that among Aboriginal patients with chronic airway diseases, ICS is the most common inhaled pharmacotherapy prescribed. Although LAMA/LABA and concurrent ICS use may be appropriate among patients with asthma and COPD, the use of ICS may have detrimental effects among those with underlying bronchiectasis either in isolation or concurrent COPD and bronchiectasis, potentially leading to higher hospital admission rates.

Variations in clinical presentation and biomarkers among biopsy-proven lupus nephritis patients: a Top End retrospective cohort study.

BACKGROUND: Lupus nephritis (LN) is a common feature of systemic lupus erythematosus (SLE) and affects 50% of patients with SLE. Racial differences in incidence and prevalence have been well documented worldwide. In Australia, higher incidence and prevalence of SLE had been previously reported in Aboriginal and Torres Strait Australians compared with non-Indigenous Australians. AIM: To describe the differences in clinical features and lupus biomarkers between Aboriginal and Torres Strait Islander Australian and non-Indigenous Australian patients with LN. METHODS: We retrospectively identified all consecutive biopsy-proven LN patients in our institution and compared the clinical features and lupus biomarkers between Aboriginal and Torres Strait Islander Australians and non-Indigenous Australians. RESULTS: Of the 33 consecutive biopsy-proven LN patients, 26 self-identified as of Aboriginal and Torres Strait Islander descent. The estimated incidence of LN in Aboriginal and Torres Strait Islander Australian and non-Indigenous Australians were 5.08 and 0.47 per 100 000 patient-years respectively. Neurological manifestations (23.08% vs 0%), haematological manifestations (46.50% vs 16.67) and right-heart catheter proven pulmonary arterial hypertension (23.08% vs 0%) were more frequently observed among Indigenous Australian patients compared with non-Indigenous Australian patients. The incidence of positive extractable nuclear antigen was also higher among Indigenous Australian patients (84.62% vs 57.14%). CONCLUSION: The present study further supports the observation that lupus in Aboriginal and Torres Strait Islander Australians were of a 'distinct phenotype' compared with non-Indigenous Australians. Future research should be aimed at delineating the reason for this observed difference.

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.

Histopathology pattern and survival analysis of patients with kidney biopsy in the top end of Northern Australia from 2007 to 2020.

AIM: Royal Darwin Hospital (RDH) is the main tertiary hospital that has performed more than 600 biopsies since its establishment. Although Indigenous people in Australia's Northern Territory (NT) has the highest rate of renal replacement therapy, the histopathology pattern of their renal diseases is still under discussed. We aimed to analyse the histopathology pattern of patients undergoing renal biopsy in RDH from June 2007 to June 2020. Secondary aims include clinical indication and survival analysis of patients with kidney biopsies. METHODS: We conducted a retrospective cohort study on all native kidney biopsy reports from patients over the age of 16, from June 2007 to June 2020. Descriptive statistics was used to summarise age, sex, indigeneity, histopathological pattern, and mortality. Categorical values were expressed as absolute frequencies and percentages. Survival analysis was performed using multivariate analyses and Cox proportional hazard regression model. RESULTS: There were 364 native renal biopsies included in the analysis. Sub-nephrotic proteinuria was the most common clinical indication for kidney biopsy (n = 160,47.8%). Diabetes nephropathy (DN) was the most common pathological finding (n = 71,12.8%). Indigenous population who had dialysis performs poorly compared to their non-indigenous counterpart (HR 2.37,95% CI 1.53-3.67,p < 0.001). CONCLUSION: Diabetic nephropathy is the most common native kidney biopsy in the NT with higher mortality among indigenous patients. This study supports the previous findings of indigenous female excess, younger age of kidney disease requiring kidney biopsy, and excess of diabetic nephropathy in the top-end of the NT. It can be speculated that some diabetic patients had atypical features prompting a biopsy.

Development and validation of algorithms to identify patients with chronic kidney disease and related chronic diseases across the Northern Territory, Australia.

BACKGROUND: Electronic health records can be used for population-wide identification and monitoring of disease. The Territory Kidney Care project developed algorithms to identify individuals with chronic kidney disease (CKD) and several commonly comorbid chronic diseases. This study aims to describe the development and validation of our algorithms for CKD, diabetes, hypertension, and cardiovascular disease. A secondary aim of the study was to describe data completeness of the Territory Kidney Care database. METHODS: The Territory Kidney Care database consolidates electronic health records from multiple health services including public hospitals (n = 6) and primary care health services (> 60) across the Northern Territory, Australia. Using the database (n = 48,569) we selected a stratified random sample of patients (n = 288), which included individuals with mild to end-stage CKD. Diagnostic accuracy of the algorithms was tested against blinded manual chart reviews. Data completeness of the database was also described. RESULTS: For CKD defined as CKD stage 1 or higher (eGFR of any level with albuminuria or persistent eGFR < 60 ml/min/1.732, including renal replacement therapy) overall algorithm sensitivity was 93% (95%CI 89 to 96%) and specificity was 73% (95%CI 64 to 82%). For CKD defined as CKD stage 3a or higher (eGFR < 60 ml/min/1.732) algorithm sensitivity and specificity were 93% and 97% respectively. Among the CKD 1 to 5 staging algorithms, the CKD stage 5 algorithm was most accurate with > 99% sensitivity and specificity. For related comorbidities - algorithm sensitivity and specificity results were 75% and 97% for diabetes; 85% and 88% for hypertension; and 79% and 96% for cardiovascular disease. CONCLUSIONS: We developed and validated algorithms to identify CKD and related chronic diseases within electronic health records. Validation results showed that CKD algorithms have a high degree of diagnostic accuracy compared to traditional administrative codes. Our highly accurate algorithms present new opportunities in early kidney disease detection, monitoring, and epidemiological research.

Induction therapy and outcome of proliferative lupus nephritis in the top end of Northern Australia - a single centre study retrospective study.

BACKGROUND: Lupus nephritis is a common manifestation of Systemic Lupus Erythematosus. Mycophenolate is recommended by guidelines for induction therapy in patients with proliferative lupus nephritis and nephrotic range proteinuria Class V lupus nephritis. Indigenous Australians suffer disproportionally from systemic lupus erythematosus compared to non-Indigenous Australians (Anstey et al., Aust N Z J Med 23:646-651, 1993; Segasothy et al., Lupus 10:439-444, 2001; Bossingham, Lupus 12:327-331, 2003; Grennan et al., Aust N Z J Med 25:182-183, 1995). METHODS: We retrospectively identified patients with newly diagnosed biopsy-proven class III lupus nephritis, class IV lupus nephritis and class V lupus nephritis with nephrotic range proteinuria from 1st Jan 2010 to 31st Dec 2019 in our institution and examined for the patterns of prescribed induction therapy and clinical outcome. The primary efficacy outcome of interest was the incidence of complete response (CR) and partial response (PR) at one-year post diagnosis as defined by the Kidney Disease: Improving Global Outcome (KDIGO) guideline. Secondary efficacy outcome was a composite of renal adverse outcome in the follow-up period. Adverse effect outcome of interest was any hospitalisations secondary to infections in the follow-up period. Continuous variables were compared using Student's t-test or Mann-Whitney U-test. Categorical variables were summarised using frequencies and percentages and assessed by Fisher's exact test. Time-to-event data was compared using the Kaplan-Meier method and Log-rank test. Count data were assessed using the Poisson's regression method and expressed as incident rate ratio. RESULTS: Twenty of the 23 patients included in the analysis were managed with mycophenolate induction upfront. Indigenous Australian patients (N = 15), compared to non-Indigenous patients (N = 5) received lower cumulative dose of mycophenolate mofetil over the 24 weeks (375 g vs. 256 g, p < 0.05), had a non-significant lower incidence of complete remission at 12 months (60% vs. 40%, p = 0.617), higher incidence of composite renal adverse outcome (0/5 patients vs. 5/15 patients, p = 0.20) and higher incidence of infection related hospitalisations, (incident rate ratio 3.66, 95% confidence interval 0.89-15.09, p = 0.073). CONCLUSION: Mycophenolate as upfront induction in Indigenous Australian patients were associated with lower incidence of remission and higher incidence of adverse outcomes. These observations bring the safety and efficacy profile of mycophenolate in Indigenous Australians into question.

Barriers and enablers to implementing and using clinical decision support systems for chronic diseases: a qualitative systematic review and meta-aggregation.

BACKGROUND: Clinical decision support (CDS) is increasingly used to facilitate chronic disease care. Despite increased availability of electronic health records and the ongoing development of new CDS technologies, uptake of CDS into routine clinical settings is inconsistent. This qualitative systematic review seeks to synthesise healthcare provider experiences of CDS-exploring the barriers and enablers to implementing, using, evaluating, and sustaining chronic disease CDS systems. METHODS: A search was conducted in Medline, CINAHL, APA PsychInfo, EconLit, and Web of Science from 2011 to 2021. Primary research studies incorporating qualitative findings were included if they targeted healthcare providers and studied a relevant chronic disease CDS intervention. Relevant CDS interventions were electronic health record-based and addressed one or more of the following chronic diseases: cardiovascular disease, diabetes, chronic kidney disease, hypertension, and hypercholesterolaemia. Qualitative findings were synthesised using a meta-aggregative approach. RESULTS: Thirty-three primary research articles were included in this qualitative systematic review. Meta-aggregation of qualitative data revealed 177 findings and 29 categories, which were aggregated into 8 synthesised findings. The synthesised findings related to clinical context, user, external context, and technical factors affecting CDS uptake. Key barriers to uptake included CDS systems that were simplistic, had limited clinical applicability in multimorbidity, and integrated poorly into existing workflows. Enablers to successful CDS interventions included perceived usefulness in providing relevant clinical knowledge and structured chronic disease care; user confidence gained through training and post training follow-up; external contexts comprised of strong clinical champions, allocated personnel, and technical support; and CDS technical features that are both highly functional, and attractive. CONCLUSION: This systematic review explored healthcare provider experiences, focussing on barriers and enablers to CDS use for chronic diseases. The results provide an evidence-base for designing, implementing, and sustaining future CDS systems. Based on the findings from this review, we highlight actionable steps for practice and future research. TRIAL REGISTRATION: PROSPERO CRD42020203716.

Design, effectiveness, and economic outcomes of contemporary chronic disease clinical decision support systems: a systematic review and meta-analysis.

OBJECTIVES: Electronic health record-based clinical decision support (CDS) has the potential to improve health outcomes. This systematic review investigates the design, effectiveness, and economic outcomes of CDS targeting several common chronic diseases. MATERIAL AND METHODS: We conducted a search in PubMed (Medline), EBSCOHOST (CINAHL, APA PsychInfo, EconLit), and Web of Science. We limited the search to studies from 2011 to 2021. Studies were included if the CDS was electronic health record-based and targeted one or more of the following chronic diseases: cardiovascular disease, diabetes, chronic kidney disease, hypertension, and hypercholesterolemia. Studies with effectiveness or economic outcomes were considered for inclusion, and a meta-analysis was conducted. RESULTS: The review included 76 studies with effectiveness outcomes and 9 with economic outcomes. Of the effectiveness studies, 63% described a positive outcome that favored the CDS intervention group. However, meta-analysis demonstrated that effect sizes were heterogenous and small, with limited clinical and statistical significance. Of the economic studies, most full economic evaluations (n = 5) used a modeled analysis approach. Cost-effectiveness of CDS varied widely between studies, with an estimated incremental cost-effectiveness ratio ranging between USD$2192 to USD$151 955 per QALY. CONCLUSION: We summarize contemporary chronic disease CDS designs and evaluation results. The effectiveness and cost-effectiveness results for CDS interventions are highly heterogeneous, likely due to differences in implementation context and evaluation methodology. Improved quality of reporting, particularly from modeled economic evaluations, would assist decision makers to better interpret and utilize results from these primary research studies. REGISTRATION: PROSPERO (CRD42020203716).

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.

Top End Pulmonary Hypertension Study: Understanding Epidemiology, Therapeutic Gaps and Prognosis in Remote Australian Setting.

INTRODUCTION: The Top End of Australia has a high proportion of Indigenous people with a high burden of chronic cardiac and pulmonary diseases likely to contribute to pulmonary hypertension (PH). The epidemiology of PH has not been previously studied in this region. METHODS: Patients with PH were identified from the Northern Territory echocardiography database from January 2010 to December 2015 and followed to the end of 2019 or death. Pulmonary hypertension was defined as a tricuspid regurgitation velocity ≥2.75 m/s measured by Doppler echocardiography. The aetiology of PH, as categorised by published guidelines, was determined by reviewing electronic health records. RESULTS: 1,764 patients were identified comprising 49% males and 45% Indigenous people. The prevalence of PH was 955 per 100,000 population (with corresponding prevalence of 1,587 for Indigenous people). Hypertension, atrial fibrillation, diabetes and respiratory disease were present in 85%, 45%, 41% and 39%, respectively. Left heart disease was the leading cause for PH (58%), the majority suffering from valvular disease (predominantly rheumatic). Pulmonary arterial hypertension (PAH), respiratory disease related PH, chronic thromboembolic PH (CTEPH) and unclear multifactorial PH represented 4%, 16%, 2% and 3%, respectively. Underlying causes were not identifiable in 17% of the patients. Only 31% of potentially eligible patients were on PAH-specific therapy. At census, there was 40% mortality, with major predictors being age, estimated pulmonary artery systolic pressure (ePASP) and Indigenous ethnicity. CONCLUSION: Pulmonary hypertension is prevalent in Northern Australia, with a high frequency of modifiable risk factors and other treatable conditions. Whether earlier diagnosis, interpretation and intervention improve outcomes merits further assessment.

Incident haemodialysis and outcomes in the Top End of Australia.

Objective The Northern Territory has the highest incidence of haemodialysis care for end-stage kidney disease in Australia. Although acute kidney injury (AKI) is a recognised risk for chronic kidney disease (CKD), the effect of AKI causing incident haemodialysis (iHD) is unknown. Audits identifying antecedents of iHD may inform health service planning. Thus, the aims of this study were to describe: (1) the development of an iHD recording system involving patients with AKI and CKD; and (2) the incidence, patient characteristics and mortality for patients with dialysis-requiring AKI. Methods A retrospective data linkage study was conducted using eight clinical and administrative datasets of adults receiving iHD during the period from July 2011 to December 2012 within a major northern Australian hospital for AKI without CKD (AKI), AKI in people with pre-existing CKD (AKI/CKD) and CKD (without AKI). The time to death was identified by the Northern Territory Register of deaths. Results In all, 121 iHD treatments were provided for the cohort, whose mean age was 51.5 years with 53.7% female, 68.6% Aboriginal ethnicity and 46.3% with diabetes. iHD was provided for AKI (23.1%), AKI/CKD (47.1%) and CKD (29.8%). The 90-day mortality rate was 25.6% (AKI 39.3%, AKI/CKD 22.8%, CKD 19.4%). The 3-year mortality rate was 45.5% (AKI 53.6%, AKI/CKD 22.8%, CKD 19.4%). The time between requesting data from custodians and receipt of data ranged from 15 to 1046 days. Conclusion AKI in people with pre-existing CKD was a common cause of iHD. Health service planning and community health may benefit from AKI prevention strategies and the implementation of sustainable and permanent linkages with the datasets used to monitor prospective incident haemodialysis. What is known about the topic? AKI is a risk factor for CKD. The Northern Territory has the highest national incidence rates of dialysis-dependent end-stage kidney disease, but has no audit tool describing outcomes of dialysis-requiring AKI. What does this paper add? We audited all iHD and showed 25.6% mortality within the first 90 days of iHD and 45.5% overall mortality at 3 years. AKI in people with pre-existing CKD caused 47.1% of iHD. What are the implications for practitioners? Health service planning and community health may benefit from AKI prevention strategies and the implementation of sustainable and permanent linkages with the datasets used to monitor prospective incident haemodialysis.

Pulmonary Hypertension in Central Australia: A Community-Based Cohort Study.

BACKGROUND: The burden of pulmonary hypertension (PHT) in Central Australia has not been previously studied. Our aim is to characterise the prevalence, clinical classification, and long-term survival of individuals with PHT in Central Australia. METHODS: A community-based cohort study of all individuals diagnosed with PHT in Central Australia between 2005 and 2016 was undertaken. We estimated PHT prevalence using population data, describe clinical PHT classification, and characterised long-term survival using Kaplan-Meier approaches. RESULTS: A total of 183 patients were identified (mean age 52±16years, 63% female). Of these individuals, 149 (81.4%) were of Aboriginal and Torres Strait Islander (ATSI) descent. The prevalence per 100,000 of any PHT was significantly higher In ATSI (723 [95% CI 608-839] compared to non-ATSI individuals (126 [95% CI 84-168], p<0.001). Furthermore, ATSI individuals were diagnosed at younger ages compared to non-ATSI individuals (49±15 vs 64±16years, p<0.001). Median estimated pulmonary artery systolic pressure (ePASP) was higher in patients with pulmonary arterial hypertension (PAH) compared to other causes (62 [IQR 54-69] vs 50 [IQR 44-58] mmHg, p<0.01). The median survival rate from diagnosis was 9 years (IQR 7.2-13.2). Age and ePASP were significant predictors of mortality (HR 1.05 [95% CI 1.02-1.07] and HR 1.56 [95% 1.00-2.42] respectively). CONCLUSIONS: In this community based study, we found a high burden of PHT in Central Australia. The prevalence of PHT is greater in ATSI individuals and is diagnosed at younger ages compared to non-ATSI individuals. Together with other cardiovascular diseases, PHT may be in-part contributing to the gap in life expectancy between ATSI and non-ATSI individuals.

Ultrastructural identification of a proximal tubulopathy without crystals in a relapsed multiple myeloma patient.

A multiple myeloma patient, who had been treated with a hematopoietic stem cell transplant, underwent a renal biopsy for investigation of a possible relapse of disease as indicated by increased serum creatinine and positive urinary Bence-Jones protein containing increased kappa light chain. Paraprotein-related renal disease was not evident by light microscopy or immunofluorescence microscopy however electron microscopy demonstrated a proximal tubulopathy with intracytoplasmic non-crystalline inclusions. The ultrastructural findings suggested possible end-organ involvement by the disease and follow-up studies subsequently revealed a relapsed multiple myeloma in the patient. The case exemplifies the usefulness of electron microscopy in detecting paraproteins that, in some instances, may be difficult to demonstrate by other techniques.