ORCID Profile
0000-0001-7528-9230
Current Organisations
The University of Auckland
,
Waitemata District Health Board
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Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: Massachusetts Medical Society
Date: 25-06-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-03-2020
Abstract: Because fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality, there is a global trend to use low-sodium dialysate in hemodialysis with the goal of reducing fluid overload. To investigate whether lower dialysate sodium during hemodialysis improves left ventricular mass, the authors conducted a randomized clinical trial of 99 adults that compared use of low-sodium dialysate (135 mM) with conventional dialysate (140 mM) for 12 months. Although participants with lower dialysate sodium showed significant improvement in fluid status, the intervention had no effect on left ventricular mass index. The intervention also increased intradialytic hypotension. Given these findings, the current trend to lower dialysate sodium should be reassessed, pending the results of large trials with hard clinical end points. Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality. There is a global trend to lower dialysate sodium with the goal of reducing fluid overload. To investigate whether lower dialysate sodium during hemodialysis reduces left ventricular mass, we conducted a randomized trial in which patients received either low-sodium dialysate (135 mM) or conventional dialysate (140 mM) for 12 months. We included participants who were aged years old, had a predialysis serum sodium ≥135 mM, and were receiving hemodialysis at home or a self-care satellite facility. Exclusion criteria included hemodialysis frequency .5 times per week and use of sodium profiling or hemodiafiltration. The main outcome was left ventricular mass index by cardiac magnetic resonance imaging. The 99 participants had a median age of 51 years old 67 were men, 31 had diabetes mellitus, and 59 had left ventricular hypertrophy. Over 12 months of follow-up, relative to control, a dialysate sodium concentration of 135 mmol/L did not change the left ventricular mass index, despite significant reductions at 6 and 12 months in interdialytic weight gain, in extracellular fluid volume, and in plasma B-type natriuretic peptide concentration (ratio of intervention to control). The intervention increased intradialytic hypotension (odds ratio [OR], 7.5 95% confidence interval [95% CI], 1.1 to 49.8 at 6 months and OR, 3.6 95% CI, 0.5 to 28.8 at 12 months). Five participants in the intervention arm could not complete the trial because of hypotension. We found no effect on health-related quality of life measures, perceived thirst or xerostomia, or dietary sodium intake. Dialysate sodium of 135 mmol/L did not reduce left ventricular mass relative to control, despite improving fluid status. The Australian New Zealand Clinical Trials Registry, ACTRN12611000975998.
Publisher: BMJ
Date: 24-06-2020
DOI: 10.1136/ANNRHEUMDIS-2019-216863
Abstract: Evaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial. Patients relapsing with granulomatosis with polyangiitis or microscopic polyangiitis were prospectively enrolled and received remission-induction therapy with rituximab (4×375 mg/m 2 ) and a higher or lower dose glucocorticoid regimen, depending on physician choice: reducing from either 1 mg/kg/day or 0.5 mg/kg/day to 10 mg/day by 4 months. Patients in this cohort achieving remission were subsequently randomised to receive one of two regimens to prevent relapse. 188 patients were studied: 95/188 (51%) men, median age 59 years (range 19–89), prior disease duration 5.0 years (range 0.4–34.5). 149/188 (79%) had previously received cyclophosphamide and 67/188 (36%) rituximab. 119/188 (63%) of relapses had at least one major disease activity item, and 54/188 (29%) received the higher dose glucocorticoid regimen. 171/188 (90%) patients achieved remission by 4 months. Only six patients (3.2% of the study population) did not achieve disease control at month 4. Four patients died in the induction phase due to pneumonia (2), cerebrovascular accident (1), and active vasculitis (1). 41 severe adverse events occurred in 27 patients, including 13 severe infections. This large prospective cohort of patients with relapsing AAV treated with rituximab in conjunction with glucocorticoids demonstrated a high level of efficacy for the reinduction of remission in patients with AAV who have relapsed, with a similar safety profile to previous studies.
Publisher: SAGE Publications
Date: 09-2017
Abstract: The HONEYPOT trial failed to establish the superiority of exit-site application of Medihoney compared with nasal mupirocin prophylaxis for the prevention of peritonitis in peritoneal dialysis (PD) patients. This study aimed to assess the representativeness of the patients in the HONEYPOT trial to the Australian and New Zealand PD population. This study compared baseline characteristics of the 371 PD patients in the HONEYPOT trial with those of 6,085 PD patients recorded on the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Compared with the PD population, the HONEYPOT s le was older (standardized difference [ d] = 0.19, p = 0.003), more likely to be treated with automated PD ( d = 0.58, p 0.001), had higher residual renal function ( d = 0.26, p 0.001) and a higher proportion of participants with end-stage kidney disease due to polycystic kidney disease ( d = 0.17) and lower proportion due to diabetes ( d = -0.17) and glomerulonephritis ( d = -0.18) ( p 0.001), and lower proportions of indigenous people ( d = -0.17, p 0.001), current smokers ( d = -0.10, p 0.001), and people with prior histories of hemodialysis ( d = -0.16, p 0.001), diabetes mellitus ( d = -0.18, p 0.001), and coronary artery disease ( d = -0.15, p 0.001). HONEYPOT trial participants tended to be healthier than the Australian and New Zealand PD patient population. Although the differences between the groups were generally modest, it is possible that their cumulative effect may have had some impact on external generalizability, which is not an uncommon occurrence in clinical trials.
Publisher: Wiley
Date: 27-03-2019
DOI: 10.1111/NEP.13236
Abstract: Poor sleep quality is common in haemodialysis patients and associated with worse outcomes. In this pre-specified analysis, we examined the impact of extended hours haemodialysis on sleep quality. The ACTIVE Dialysis trial randomized 200 participants to extended (≥24 h/week) or standard (target 12-15 h) hours haemodialysis over 12 months. Sleep quality was measured in the Kidney Disease Quality of Life Short Form 1.3 (KDQOL-SF) by overall sleep quality score (0-10, 10 = 'very good') and the sleep subscale (0-100, 100 = 'best possible sleep') every 3 months via blinded telephone interview. The average intervention effect was calculated by mixed linear regression adjusted by time point and baseline score. Factors predicting sleep quality were assessed by multivariate regression analysis. Overall sleep quality score and sleep subscale at baseline were similar in both groups (5.9 [95%CI 5.4-6.4] vs. 6.3 [5.9-6.8] 65.0 [60.9-69.1] vs. 63.2 [59.1-67.3] extended and standard hours, respectively). Extended hours haemodialysis led to a non-significant improvement in overall sleep quality score (average intervention effect 0.44 (-0.01 to 0.89), P = 0.053) and sleep subscale (average intervention effect 3.58 (-0.02 to 7.18), P = 0.051). Poor sleep quality was associated with being female and with current smoking. Sleep quality was positively associated with EuroQol-5D (EQ5D) and the SF-36 Physical Component and Mental Component Summary Scores but not with hospitalizations. Sleep quality was not significantly improved by extended hours dialysis in this study. Sleep quality is positively correlated with quality of life in haemodialysis patients and is poorer in women and current smokers.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Oxford University Press (OUP)
Date: 15-09-2014
DOI: 10.1093/NDT/GFT378
Abstract: Non-randomized studies suggest an association between serum uric acid levels and progression of chronic kidney disease (CKD). The aim of this systematic review is to summarize evidence from randomized controlled trials (RCTs) concerning the benefits and risks of uric acid-lowering therapy on renal outcomes. Medline, Excerpta Medical Database and Cochrane Central Register of Controlled Trials were searched with English language restriction for RCTs comparing the effect of uric acid-lowering therapy with placebo/no treatment on renal outcomes. Treatment effects were summarized using random-effects meta-analysis. Eight trials (476 participants) evaluating allopurinol treatment were eligible for inclusion. There was substantial heterogeneity in baseline kidney function, cause of CKD and duration of follow-up across these studies. In five trials, there was no significant difference in change in glomerular filtration rate from baseline between the allopurinol and control arms [mean difference (MD) 3.1 mL/min/1.73 m2, 95% confidence intervals (CI) -0.9, 7.1 heterogeneity χ2=1.9, I2=0%, P=0.75]. In three trials, allopurinol treatment abrogated increases in serum creatinine from baseline (MD -0.4 mg/dL, 95% CI -0.8, -0.0 mg/dL heterogeneity χ2=3, I2=34%, P=0.22). Allopurinol had no effect on proteinuria and blood pressure. Data for effects of allopurinol therapy on progression to end-stage kidney disease and death were scant. Allopurinol had uncertain effects on the risks of adverse events. Uric acid-lowering therapy with allopurinol may retard the progression of CKD. However, adequately powered randomized trials are required to evaluate the benefits and risks of uric acid-lowering therapy in CKD.
Publisher: National Institute for Health and Care Research
Date: 09-2022
DOI: 10.3310/PNXB5040
Abstract: Anti-neutrophil cytoplasm antibody-associated vasculitis is a multisystem, autoimmune disease that causes organ failure and death. Physical removal of pathogenic autoantibodies by plasma exchange is recommended for severe presentations, along with high-dose glucocorticoids, but glucocorticoid toxicity contributes to morbidity and mortality. The lack of a robust evidence base to guide the use of plasma exchange and glucocorticoid dosing contributes to variation in practice and suboptimal outcomes. We aimed to determine the clinical efficacy of plasma exchange in addition to immunosuppressive therapy and glucocorticoids with respect to death and end-stage renal disease in patients with severe anti-neutrophil cytoplasm antibody-associated vasculitis. We also aimed to determine whether or not a reduced-dose glucocorticoid regimen was non-inferior to a standard-dose regimen with respect to death and end-stage renal disease. This was an international, multicentre, open-label, randomised controlled trial. Patients were randomised in a two-by-two factorial design to receive either adjunctive plasma exchange or no plasma exchange, and either a reduced or a standard glucocorticoid dosing regimen. All patients received immunosuppressive induction therapy with cyclophosphamide or rituximab. Ninety-five hospitals in Europe, North America, Australia/New Zealand and Japan participated. Participants were aged ≥ 16 years with a diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis, and either proteinase 3 anti-neutrophil cytoplasm antibody or myeloperoxidase anti-neutrophil cytoplasm antibody positivity, and a glomerular filtration rate of 50 ml/minute/1.73 m 2 or diffuse alveolar haemorrhage attributable to active anti-neutrophil cytoplasm antibody-associated vasculitis. Participants received seven sessions of plasma exchange within 14 days or no plasma exchange. Oral glucocorticoids commenced with prednisolone 1 mg/kg/day and were reduced over different lengths of time to 5 mg/kg/day, such that cumulative oral glucocorticoid exposure in the first 6 months was 50% lower in patients allocated to the reduced-dose regimen than in those allocated to the standard-dose regimen. All patients received the same glucocorticoid dosing from 6 to 12 months. Subsequent dosing was at the discretion of the treating physician. The primary outcome was a composite of all-cause mortality and end-stage renal disease at a common close-out when the last patient had completed 10 months in the trial. The study recruited 704 patients from June 2010 to September 2016. Ninety-nine patients died and 138 developed end-stage renal disease, with the primary end point occurring in 209 out of 704 (29.7%) patients: 100 out of 352 (28%) in the plasma exchange group and 109 out of 352 (31%) in the no plasma exchange group (adjusted hazard ratio 0.86, 95% confidence interval 0.65 to 1.13 p = 0.3). In the per-protocol analysis for the non-inferiority glucocorticoid comparison, the primary end point occurred in 92 out of 330 (28%) patients in the reduced-dose group and 83 out of 325 (26%) patients in the standard-dose group (partial-adjusted risk difference 0.023, 95% confidence interval 0.034 to 0.08 p = 0.5), thus meeting our non-inferiority hypothesis. Serious infections in the first year occurred in 96 out of 353 (27%) patients in the reduced-dose group and in 116 out of 351 (33%) patients in the standard-dose group. The rate of serious infections at 1 year was lower in the reduced-dose group than in the standard-dose group (incidence rate ratio 0.69, 95% confidence interval 0.52 to 0.93 p = 0.016). Plasma exchange did not prolong the time to death and/or end-stage renal disease in patients with anti-neutrophil cytoplasm antibody-associated vasculitis with severe renal or pulmonary involvement. A reduced-dose glucocorticoid regimen was non-inferior to a standard-dose regimen and was associated with fewer serious infections. A meta-analysis examining the effects of plasma exchange on kidney outcomes in anti-neutrophil cytoplasm antibody-associated vasculitis is planned. A health-economic analysis of data collected in this study to examine the impact of both plasma exchange and reduced glucocorticoid dosing is planned to address the utility of plasma exchange for reducing early end-stage renal disease rates. Blood and tissue s les collected in the study will be examined to identify predictors of response to plasma exchange in anti-neutrophil cytoplasm in antibody-associated vasculitis. The benefits associated with reduced glucocorticoid dosing will inform future studies of newer therapies to permit further reduction in glucocorticoid exposure. Data from this study will contribute to updated management recommendations for anti-neutrophil cytoplasm antibody-associated vasculitis. This study had an open-label design which may have permitted observer bias however, the nature of the end points, end-stage renal disease and death, would have minimised this risk. Despite being, to our knowledge, the largest ever trial in anti-neutrophil cytoplasm antibody-associated vasculitis, there was an insufficient s le size to assess clinically useful benefits on the separate components of the primary end-point: end-stage renal disease and death. Use of a fixed-dose plasma exchange regimen determined by consensus rather than data-driven dose ranging meant that some patients may have been underdosed, thus reducing the therapeutic impact. In particular, no biomarkers have been identified to help determine dosing in a particular patient, although this is one of the goals of the biomarker plan of this study. This trial is registered as ISRCTN07757494, EudraCT 2009-013220-24 and Clinicaltrials.gov NCT00987389. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 26, No. 38. See the NIHR Journals Library website for further project information.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2017
Abstract: The relationship between increased hemodialysis hours and patient outcomes remains unclear. We randomized (1:1) 200 adult recipients of standard maintenance hemodialysis from in-center and home-based hemodialysis programs to extended weekly (≥24 hours) or standard (target 12–15 hours, maximum 18 hours) hemodialysis hours for 12 months. The primary outcome was change in quality of life from baseline assessed by the EuroQol 5 dimension instrument (3 level) (EQ-5D). Secondary outcomes included medication usage, clinical laboratory values, vascular access events, and change in left ventricular mass index. At 12 months, median weekly hemodialysis hours were 24.0 (interquartile range, 23.6–24.0) and 12.0 (interquartile range, 12.0–16.0) in the extended and standard groups, respectively. Change in EQ-5D score at study end did not differ between groups (mean difference, 0.04 [95% confidence interval, −0.03 to 0.11] P =0.29). Extended hours were associated with lower phosphate and potassium levels and higher hemoglobin levels. Blood pressure (BP) did not differ between groups at study end. Extended hours were associated with fewer BP-lowering agents and phosphate-binding medications, but were not associated with erythropoietin dosing. In a substudy with 95 patients, we detected no difference between groups in left ventricular mass index (mean difference, −6.0 [95% confidence interval, −14.8 to 2.7] g/m 2 P =0.18). Five deaths occurred in the extended group and two in the standard group ( P =0.44) two participants in each group withdrew consent. Similar numbers of patients experienced vascular access events in the two groups. Thus, extending weekly hemodialysis hours did not alter overall EQ-5D quality of life score, but was associated with improvement in some laboratory parameters and reductions in medication burden. (Clinicaltrials.gov identifier: NCT00649298).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-10-2019
DOI: 10.2215/CJN.06800619
Abstract: Little is known about the effect of changes in dialysis hours on patient-reported outcome measures. We report the effect of doubling dialysis hours on a range of patient-reported outcome measures in a randomized trial, overall and separately for important subgroups. The A Clinical Trial of IntensiVE Dialysis trial randomized 200 participants to extended or standard weekly hours hemodialysis for 12 months. Patient-reported outcome measures included two health utility scores (EuroQOL-5 Dimensions-3 Level, Short Form-6 Dimension) and their derived quality-adjusted life year estimates, two generic health scores (Short Form-36 Physical Component Summary, Mental Component Summary), and a disease-specific score (Kidney Disease Component Score). Outcomes were assessed as the mean difference from baseline using linear mixed effects models adjusted for time point and baseline score, with interaction terms added for subgroup analyses. Prespecified subgroups were dialysis location (home- versus institution-based), dialysis vintage (≤6 months versus months), region (China versus Australia, New Zealand, Canada), and baseline score (lowest, middle, highest tertile). Multiplicity-adjusted P values (Holm–Bonferroni) were calculated for the main analyses. Extended dialysis hours was associated with improvement in Short Form-6 Dimension (mean difference, 0.027 95% confidence interval [95% CI], 0.00 to 0.05 P =0.03) which was not significant after adjustment for multiple comparisons ( Padjusted =0.05). There were no significant differences in EuroQOL-5 Dimensions-3 Level health utility (mean difference, 0.036 95% CI, −0.02 to 0.09 P =0.2 Padjusted =0.2) or in quality-adjusted life years. There were small positive differences in generic and disease-specific quality of life: Physical Component Summary (mean difference, 2.3 95% CI, 0.6 to 4.1 P =0.01 Padjusted =0.04), Mental Component Summary (mean difference, 2.5 95% CI, 0.5 to 4.6 P =0.02 Padjusted =0.05) and Kidney Disease Component Score (mean difference, 3.5 95% CI, 1.5 to 5.5 P =0.001 Padjusted =0.005). The results did not differ among predefined subgroups or by baseline score. The effect of extended hours hemodialysis on patient-reported outcome measures reached statistical significance in some but not all measures. Within each measure the effect was consistent across predefined subgroups. The clinical importance of these differences is unclear.
Publisher: BMJ
Date: 05-01-2019
DOI: 10.1136/ANNRHEUMDIS-2018-214245
Abstract: Cyclophosphamide induction regimens are effective for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but are associated with infections, malignancies and infertility. Mycophenolate mofetil (MMF) has shown high remission rates in small studies of AAV. We conducted a randomised controlled trial to investigate whether MMF was non-inferior to cyclophosphamide for remission induction in AAV. 140 newly diagnosed patients were randomly assigned to MMF or pulsed cyclophosphamide. All patients received the same oral glucocorticoid regimen and were switched to azathioprine following remission. The primary endpoint was remission by 6 months requiring compliance with the tapering glucocorticoid regimen. Patients with an eGFR mL/min were excluded from the study. At baseline, ANCA subtype, disease activity and organ involvement were similar between groups. Non-inferiority was demonstrated for the primary remission endpoint, which occurred in 47 patients (67%) in the MMF group and 43 patients (61%) in the cyclophosphamide group (risk difference 5.7%, 90% CI −7.5% to 19%). Following remission, more relapses occurred in the MMF group (23 patients, 33%) compared with the cyclophosphamide group (13 patients, 19%) (incidence rate ratio 1.97, 95% CI 0.96 to 4.23, p=0.049). In MPO-ANCA patients, relapses occurred in 12% of the cyclophosphamide group and 15% of the MMF group. In PR3-ANCA patients, relapses occurred in 24% of the cyclophosphamide group and 48% of the MMF group. Serious infections were similar between groups (26% MMF group, 17% cyclophosphamide group) (OR 1.67, 95% CI 0.68 to 4.19, p=0.3). MMF was non-inferior to cyclophosphamide for remission induction in AAV, but resulted in higher relapse rate. NCT00414128 .
Publisher: Massachusetts Medical Society
Date: 13-02-2020
Publisher: Massachusetts Medical Society
Date: 18-02-2021
No related grants have been discovered for Janak de Zoysa.