Search

Objective: Relapses of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis are important events that can cause organ dysfunction and reduce quality of life. Understanding the effects of the initial treatments for ANCA‐associated vasculitis on the subsequent risk of relapse may help guide monitoring and treatment. Methods: We performed a post hoc analysis of participants with severe ANCA‐associated vasculitis enrolled in an international two‐by‐two factorial randomized controlled trial comparing the effects of plasma exchange (PLEX) to no PLEX and a regimen of reduced glucocorticoid exposure to a standard regimen. We estimated the effects of treatments on relapses of any severity using three competing risk time‐to‐event models adjusted for patient and disease characteristics and other treatments. Each model was adjusted for disease manifestations in different ways. Results: Of 704 participants, 649 (92.2%) achieved remission and 147 (22.7%) experienced 204 relapses. The relapse rate was 10.3 (95% confidence interval [CI] 8.4–12.1) relapses per 100 patient‐years. Neither the use of PLEX (subhazard ratio 0.91–0.94; 95% CIs range from 0.66 to 1.31) nor a glucocorticoid regimen (subhazard ratio 0.93–0.94; 95% CIs range from 0.67 to 1.35) appreciably changed the risk of relapse. Proteinase 3–ANCA and the presence of nonhemorrhagic respiratory manifestations of the disease at trial entry were associated with increased risks of relapse. Receiving dialysis at baseline and administration of oral cyclophosphamide as induction therapy were associated with lower risks of relapse. Conclusion: In patients with severe ANCA‐associated vasculitis, relapses remain common; neither the use of PLEX nor an initial glucocorticoid tapering regimen impacted relapse risk. [ABSTRACT FROM AUTHOR]

Background: Dietary management plays an important role in patients with kidney failure. Current dietary habits of Australians and New Zealanders (ANZ) and Malaysians with chronic kidney disease (CKD Stage 4–5) have not been adequately investigated. We report the dietary habits of people with advanced CKD and their adherence to country‐specific dietary guidelines. Methods: Participants with CKD Stage 4–5, enrolled in the Omega‐3 Fatty Acids (Fish oils) and Aspirin in Vascular access Outcomes in Renal Disease (FAVOURED) trial, completed a lifestyle questionnaire at baseline on their dietary intake. Results: Of 567 participants, 538 (ANZ, n = 386; Malaysian, n = 152; mean ± SD age 54.8 ± 14.3 years, 64% male) completed the questionnaire. Dietary fruit and vegetable intakes were higher in ANZ participants; 49% (n = 189) consumed ≥2 serves day–1 of fruit and 61% (n = 235) ate ≥2 serves day–1 of vegetables compared to 24% (n = 36) and 34% (n = 52) of Malaysians, respectively (p < 0.0001). Only 4% (n = 15) of ANZ participants met Australian Dietary recommendations of two fruit and five vegetable serves day–1. Fish consumption was higher in Malaysians with 83% (n = 126) consuming ≥2 serves week–1 compared to 21% (n = 81) of ANZ participants (p < 0.001). Red meat intake was higher in ANZ participants; however, chicken consumption was similar; 48% (n = 185) consumed >2 chicken serves week–1 and 65% (n = 251) ate >2 serves week–1 of red meat compared to 43% (n = 65) and 15% (n = 23) of Malaysians, respectively. Conclusions: Significant regional variation in dietary intake for fruit, vegetables and animal protein is described that likely reflects cultural and economic differences. Barriers to meeting recommended dietary intakes require further investigation. Key Points: Dietary management plays an important role in the management of patients with kidney failure.Current dietary habits of Australians, New Zealanders and Malaysians with advanced chronic kidney disease have not been adequately investigated.Dietary fruit and vegetable intakes were significantly higher in Australia and New Zealand (ANZ) participants then Malaysian participants.Fish consumption was higher in Malaysians compared to ANZ participants.The significant regional variation in dietary intake for fruit, vegetables and animal protein likely reflects cultural and economic differences.Dietary intakes of both fruit and vegetables were inadequate by national recommendations but similar to the general population in both the ANZ and Malaysia cohorts.Barriers to meeting recommended dietary intakes require further investigation. [ABSTRACT FROM AUTHOR]

The unprecedented demand placed on healthcare systems from the COVID-19 pandemic has forced a reassessment of clinical trial conduct and feasibility. Consequently, the Australasian Kidney Trials Network (AKTN), an established collaborative research group known for conducting investigator-initiated global clinical trials, had to efficiently respond and adapt to the changing landscape during COVID-19. Key priorities included ensuring patient and staff safety, trial integrity and network sustainability for the kidney care community. New resources have been developed to enable a structured review and contingency plan of trial activities during the pandemic and beyond. [ABSTRACT FROM AUTHOR]

Abstract Background Haemodialysis (HD) is critically dependent on the availability of adequate access to the systemic circulation, ideally via a native arteriovenous fistula (AVF). The Primary failure rate of an AVF ranges between 20–54%, due to thrombosis or failure of maturation. There remains limited evidence for the use of anti-platelet agents and uncertainty as to choice of agent(s) for the prevention of AVF thrombosis. We present the study protocol for a randomised, double-blind, placebo-controlled, clinical trial examining whether the use of the anti-platelet agents, aspirin and omega-3 fatty acids, either alone or in combination, will effectively reduce the risk of early thrombosis in de novo AVF. Methods/Design The study population is adult patients with stage IV or V chronic kidney disease (CKD) currently on HD or where HD is planned to start within 6 months in whom a planned upper or lower arm AVF is to be the primary HD access. Using a factorial-design trial, patients will be randomised to aspirin or matching placebo, and also to omega-3 fatty acids or matching placebo, resulting in four treatment groups (aspirin placebo/omega-3 fatty acid placebo, aspirin/omega-3 fatty acid placebo, aspirin placebo/omega-3 fatty acid, aspirin/omega-3 fatty acid). Randomisation will be achieved using a dynamic balancing method over the two stratification factors of study site and upper versus lower arm AVF. The medication will be commenced pre-operatively and continued for 3 months post surgery. The primary outcome is patency of the AVF at three months after randomisation. Secondary outcome measures will include functional patency at six and twelve months, primary patency time, secondary (assisted) patency time, and adverse events, particularly bleeding. Discussion This multicentre Australian and New Zealand study has been designed to determine whether the outcome of surgery to create de novo AVF can be improved by the use of aspirin and/or omega-3 fatty acids. Recently a placebo-controlled trial has shown that clopidogrel is effective in safely preventing primary AVF thrombosis, but ineffective at increasing functional patency. Our study presents significant differences in the anti-platelet agents used, the study design, and surgical and patient demographics that should contribute further evidence regarding the efficacy of anti-platelet agents. Trial Registration Australia & New Zealand Clinical Trials Register (ACTRN12607000569404).

Background: Arteriovenous fistulas (AVF) for haemodialysis often experience early thrombosis and maturation failure requiring intervention and/or central venous catheter (CVC) placement. This secondary and exploratory analysis of the FAVOURED study determined whether omega-3 fatty acids (fish oils) or aspirin affected AVF usability, intervention rates and CVC requirements. Methods: In 567 adult participants planned for AVF creation, all were randomised to fish oil (4g/d) or placebo, and 406 to aspirin (100mg/d) or placebo, starting one day pre-surgery and continued for three months. Outcomes evaluated within 12 months included AVF intervention rates, CVC exposure, late dialysis suitability failure, and times to primary patency loss, abandonment and successful cannulation. Results: Final analyses included 536 participants randomised to fish oil or placebo (mean age 55 years, 64% male, 45% diabetic) and 388 randomised to aspirin or placebo. Compared with placebo, fish oil reduced intervention rates (0.82 vs 1.14/1000 patient-days, incidence rate ratio [IRR] 0.72, 95% confidence interval [CI] 0.54–0.97), particularly interventions for acute thrombosis (0.09 vs 0.17/1000 patient-days, IRR 0.53, 95% CI 0.34–0.84). Aspirin significantly reduced rescue intervention rates (IRR 0.45, 95% CI 0.27–0.78). Neither agent significantly affected CVC exposure, late dialysis suitability failure or time to primary patency loss, AVF abandonment or successful cannulation. Conclusion: Although fish oil and low-dose aspirin given for 3 months reduced intervention rates in newly created AVF, they had no significant effects on CVC exposure, AVF usability and time to primary patency loss or access abandonment. Reduction in access interventions benefits patients, reduces costs and warrants further study. [ABSTRACT FROM AUTHOR]

Background: The FAVOURED study is an international multicentre, double-blind, placebo-controlled trial which commenced recruitment in 2008 and examines whether omega-3 polyunsaturated fatty acids (omega-3 PUFAs) either alone or in combination with aspirin will effectively reduce primary access failure of de novo arteriovenous fistulae (AVF) in patients with stage 4 and 5 chronic kidney disease. Publication of new evidence derived from additional studies of clopidogrel and a high screen failure rate due to prevalent aspirin usage prompted an updated trial design. Methods/design: The original trial protocol published in 2009 has undergone two major amendments, which were implemented in 2011. Firstly, the primary outcome 'early thrombosis' at 3 months following AVF creation was broadened to a more clinically relevant outcome of 'AVF access failure'; a composite of thrombosis, AVF abandonment and cannulation failure at 12 months. Secondly, participants unable to cease using aspirin were allowed to be enrolled and randomised to omega-3 PUFAs or placebo. The revised primary aim of the FAVOURED study is to test the hypothesis that omega-3 PUFAs will reduce rates of AVF access failure within 12 months following AVF surgery. The secondary aims are to examine the effect of omega-3 PUFAs and aspirin on the individual components of the primary end-point, to examine the safety of study interventions and assess central venous catheter requirement as a result of access failure. Discussion: This multicentre international clinical trial was amended to address the clinically relevant question of whether the usability of de novo AVF at 12 months can be improved by the early use of omega-3 PUFAs and to a lesser extent aspirin. This study protocol amendment was made in response to a large trial demonstrating that clopidogrel is effective in safely preventing primary AVF thrombosis, but ineffective at increasing functional patency. Secondly, including patients taking aspirin will enrol a more representative cohort of haemodialysis patients, who are significantly older with a higher prevalence of cardiovascular disease and diabetes which may increase event rates and the power of the study [ABSTRACT FROM AUTHOR]

Extracts from the seed of the African shea tree Vitellaria paradoxa C.F. Gaertn have been used traditionally for the treatment of arthritic conditions. However, little is known about the mechanisms by which benefit is conferred. This single-site, 15-week randomized, double-blind, parallel, placebo-controlled study examined a range of biomarkers in 89 patients with osteoarthritis of the knees and/or hips to determine potential modes of action of SheaFlex70TM, a triterpene-rich extract of Vitellaria paradoxa. In the group of participants with levels of osteoarthritis biomarkers in the upper quartile at baseline, there were significant decreases in inflammation and cartilage breakdown and trend level decreases in bone remodeling in the SheaFlex70TM group versus placebo between commencement and completion of the study. Inflammation marker TNF-alpha fell 23.9% vs 6% (treatment vs placebo), p = 0.041. Cartilage degradation marker CTX-II fell 28.7% vs an increase of 17.6% (treatment vs placebo), p = 0.018. This marker also showed significant falls across the entire study group, 10.6% vs an increase of 11.6%, (treatment vs placebo), p = 0.016. Osteocalcin levels fell 9.2%, p = 0.014 (treatment) vs 1.2%, ns (placebo), p = 0.096 (treatment vs placebo). These findings indicate that in patients with the highest levels of osteoarthritis biomarkers, SheaFlex70TM demonstrated multiple beneficial activities consistent with slowing the disease process. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: There is substantial variation in peritonitis rates across peritoneal dialysis (PD) units globally. This may, in part, be related to the wide variability in the content and delivery of training for PD nurse trainers and patients., Aim: The aim of this study was to test the feasibility of implementing the Targeted Education ApproaCH to improve Peritoneal Dialysis Outcomes (TEACH-PD) curriculum in real clinical practice settings., Methods: This study used mixed methods including questionnaires and semi-structured interviews (pretraining and post-training) with nurse trainers and patients to test the acceptability and usability of the PD training modules implemented in two PD units over 6 months. Quantitative data from the questionnaires were analysed descriptively. Interviews were analysed using thematic analysis., Results: Ten PD trainers and 14 incident PD patients were included. Mean training duration to complete the modules were 10.9 h (range 6-17) and 24.9 h (range 15-35), for PD trainers and patients, respectively. None of the PD patients experienced PD-related complications at 30 days follow-up. Three (21%) patients were transferred to haemodialysis due to non-PD-related complications. Ten trainers and 14 PD patients participated in the interviews. Four themes were identified including use of adult learning principles (trainers), comprehension of online modules (trainers), time to complete the modules (trainers) and patient usability of the manuals (patient)., Conclusion: This TEACH-PD study has demonstrated feasibility of implementation in a real clinical setting. The outcomes of this study have informed refinement of the TEACH-PD modules prior to rigorous evaluation of its efficacy and cost-effectiveness in a large-scale study.