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Westmead, Australia

Cody J.D.,University of Aberdeen | Hodson E.M.,Center for Kidney Research
Cochrane Database of Systematic Reviews | Year: 2016

Background: Treatment with recombinant human erythropoietin (rHuEPO) in dialysis patients has been shown to be highly effective in terms of correcting anaemia and improving quality of life. There is debate concerning the benefits of rHuEPO use in predialysis patients which may accelerate the deterioration of kidney function. However the opposing view is that if rHuEPO is as effective in predialysis patients, improving the patient's sense of well-being may result in the onset of dialysis being delayed. This is an update of a review first published in 2001 and last updated in 2005. Objectives: The objective of this review was to ascertain the effects of rHuEPO treatment in predialysis patients primarily in terms of the timing of the onset of dialysis; but also that predialysis rHuEPO: 1) corrects haemoglobin/haematocrit (markers of anaemia); 2) improves quality of life; and 3) is not associated with an increased incidence of adverse events such as hastening of the onset of dialysis, increased hypertension, clotting of arterio-venous fistulae or seizures. Search methods: We searched the Cochrane Kidney and Transplant's Specialised Register (up to 29 June 2015) through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Selection criteria: Randomised controlled trials (RCTs) or quasi-RCTs comparing the use of rHuEPO with no treatment or placebo in predialysis patients. Data collection and analysis: Only published data were used. Quality assessment was performed by two assessors independently. Data were abstracted by a single author onto a standard form, a sample of which was checked by another author. Results were expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). Main results: Nineteen studies (enrolling 993 participants) were included. Due to the age of the included studies (most performed prior to 2000) the risk of bias was judged to be unclear in the majority of the studies for most of the domains. There was an improvement in haemoglobin (MD 1.90 gm/L, 95% CI -2.34 to -1.47) and haematocrit (MD 9.85%, 95% CI 8.35 to 11.34) with treatment and a decrease in the number of patients requiring blood transfusions (RR 0.32, 95% CI 0.12 to 0.83). The data from studies reporting quality of life or exercise capacity demonstrated an improvement in the treatment group. Most of the measures of progression of kidney disease showed no statistically significant difference. No significant increase in adverse events was identified. Authors' conclusions: Treatment with rHuEPO in predialysis patients corrects anaemia, avoids the requirement for blood transfusions and also improves quality of life and exercise capacity. We were unable to assess the effects of rHuEPO on progression of kidney disease, delay in the onset of dialysis or adverse events. Based on the current evidence, decisions on the putative benefits in terms of quality of life are worth the extra costs of predialysis rHuEPO need careful evaluation. © 2016 The Cochrane Collaboration. Source


Lombel R.M.,University of Michigan | Hodson E.M.,Center for Kidney Research | Hodson E.M.,University of Sydney | Gipson D.S.,University of Michigan
Pediatric Nephrology | Year: 2013

Kidney Disease: Improving Global Outcomes (KDIGO) recently published the clinical practice guideline on glomerulonephritis (GN) to assist the practitioner caring for patients with GN. Chapter 4 of the guideline focuses on managing children aged 1-18 years with steroid-resistant nephrotic syndrome (SRNS), defined by an inability to achieve complete remission with corticosteroid therapy. Guideline development followed a thorough evidence review, and management recommendations and suggestions were based on the best available evidence. Limitations of the evidence, including the paucity of large-scale randomized controlled trials, are discussed. This article provides both the guideline recommendations and a brief review of relevant treatment trials related to each recommendation. This précis serves as a summary of the complete guidelines recently published. © 2012 IPNA. Source


Pravitsitthikul N.,Center for Kidney Research
The Cochrane database of systematic reviews | Year: 2013

About 80% to 90% of children with steroid-sensitive nephrotic syndrome (SSNS) have relapses. Of these children, around half relapse frequently, and are at risk of adverse effects from corticosteroids. Non-corticosteroid immunosuppressive medications are used to prolong periods of remission in these children; however, these medications have significant potential adverse effects. Currently, there is no consensus about the most appropriate second line agent in children who are steroid sensitive, but who continue to relapse. This is the third update of a review first published in 2001 and updated in 2005 and 2008. To evaluate the benefits and harms of non-corticosteroid immunosuppressive medications in relapsing SSNS in children. For this update we searched the Cochrane Renal Group's Specialised Register to June 2013. Randomised controlled trials (RCTs) or quasi-RCTs were included if they compared non-corticosteroid immunosuppressive medications with placebo, prednisone or no treatment, different non-corticosteroid immunosuppressive medications and different doses, durations or routes of administration of the same non-corticosteroid immunosuppressive medication. Two authors independently assessed the risk of bias of the included studies and extracted data. Statistical analyses were performed using a random-effects model and results expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). We identified 32 studies (1443 children) of which one study is still ongoing. In the 31 studies with data, risk of bias assessment indicated that 11 (37%) and 16 (53%) studies were at low risk of bias for sequence generation and allocation concealment respectively. Six (29%) studies were at low risk of performance and detection bias. Twenty seven (87%) and 19 (60%) studies were at low risk of incomplete and selective reporting respectively. Alkylating agents (cyclophosphamide and chlorambucil) significantly reduced the risk of relapse at six to 12 months (RR 0.43, 95% CI 0.31 to 0.60) and 12 to 24 months (RR 0.20, 95% CI 0.09 to 0.46) compared with prednisone alone. There was no significant difference in relapse risk at two years between chlorambucil and cyclophosphamide (RR 1.31, 95% CI 0.80 to 2.13). There was no significant difference at one year between intravenous and oral cyclophosphamide (RR 0.99, 95% CI 0.76 to 1.29). Cyclosporin was as effective as cyclophosphamide (RR 1.07, 95% CI 0.48 to 2.35) and chlorambucil (RR 0.82, 95% CI 0.44 to 1.53) at the end of therapy while levamisole (RR 0.47, 95% CI 0.24 to 0.89) was more effective than steroids alone. However the effects of cyclosporin and levamisole were not sustained once treatment was stopped. In one small study cyclosporin significantly reduced the relapse rate compared with mycophenolate mofetil (MD 0.75, 95% CI 0.01 to 1.49). Limited data from a cross-over study suggested that cyclosporin was more effective than mycophenolate mofetil in maintaining remission. In steroid- and cyclosporin-dependent disease, rituximab significantly reduced the risk of relapse at three months compared with conventional therapy. Mizoribine and azathioprine were no more effective than placebo or prednisone alone in maintaining remission. Eight-week courses of cyclophosphamide or chlorambucil and prolonged courses of cyclosporin and levamisole reduce the risk of relapse in children with relapsing SSNS compared with corticosteroids alone. Limited data indicate that mycophenolate mofetil and rituximab are valuable additional medications for relapsing SSNS. However clinically important differences in efficacy are possible and further comparative studies are still needed. Source


Hodson E.M.,Center for Kidney Research
Cochrane database of systematic reviews (Online) | Year: 2013

The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis with the aim of preventing the clinical syndrome associated with CMV infection. This is an update of a review first published in 2005 and updated in 2008. To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause mortality in solid organ transplant recipients. We searched MEDLINE, EMBASE and the Cochrane Central Registry of Controlled Trials (CENTRAL) in The Cochrane Library to February 2004 for the first version of this review. The Cochrane Renal Group's specialised register was searched to February 2007 and to July 2011 for the first and current updates of the review without language restriction. We included randomised controlled trials (RCTs) and quasi-RCTs comparing antiviral medications with placebo or no treatment, comparing different antiviral medications and comparing different regimens of the same antiviral medications in recipients of any solid organ transplant. Studies examining pre-emptive therapy were excluded. Two authors independently assessed study eligibility, risk of bias and extracted data. Results were reported as risk ratios (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes and by mean difference (MD) with 95% CI for continuous outcomes. Statistical analyses were performed using the random-effects model. Subgroup analysis and univariate meta-regression were performed using restricted maximum-likelihood to estimate the between study variance. Multivariate meta-regression was performed to investigate whether the results were altered after allowing for differences in drugs used, organ transplanted, and recipient CMV serostatus at the time of transplantation. We identified 37 studies (4342 participants). Risk of bias attributes were poorly performed or reported with low risk of bias reported for sequence generation, allocation concealment, blinding and selective outcome reporting in 25% or fewer studies.Prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment significantly reduced the risk for CMV disease (19 studies; RR 0.42, 95% CI 0.34 to 0.52), CMV infection (17 studies; RR 0.61, 95% CI 0.48 to 0.77), and all-cause mortality (17 studies; RR 0.63, 95% CI 0.43 to 0.92) primarily due to reduced mortality from CMV disease (7 studies; RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduced the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but not fungal infection, acute rejection or graft loss.Meta-regression showed no significant difference in the relative benefit of treatment (risk of CMV disease or all-cause mortality) by organ transplanted or CMV serostatus; no conclusions were possible for CMV negative recipients of negative organs.Neurological dysfunction was more common with ganciclovir and valaciclovir compared with placebo/no treatment. In direct comparison studies, ganciclovir was more effective than aciclovir in preventing CMV disease (7 studies; RR 0.37, 95% CI 0.23 to 0.60) and leucopenia was more common with aciclovir. Valganciclovir and IV ganciclovir were as effective as oral ganciclovir. The efficacy and adverse effects of valganciclovir/ganciclovir did not differ from valaciclovir in three small studies. Extended duration prophylaxis significantly reduced the risk of CMV disease compared with three months therapy (2 studies; RR 0.20, 95% CI 0.12 to 0.35). Leucopenia was more common with extended duration prophylaxis but severe treatment associated adverse effects did not differ between extended and three month durations of treatment. Prophylaxis with antiviral medications reduces CMV disease and CMV-associated mortality in solid organ transplant recipients. These data suggest that antiviral prophylaxis should be used routinely in CMV positive recipients and in CMV negative recipients of CMV positive organ transplants. Source


Sinha Y.,Center for Kidney Research
Cochrane database of systematic reviews (Online) | Year: 2011

Auditory integration therapy was developed as a technique for improving abnormal sound sensitivity in individuals with behavioural disorders including autism spectrum disorders. Other sound therapies bearing similarities to auditory integration therapy include the Tomatis Method and Samonas Sound Therapy. To determine the effectiveness of auditory integration therapy or other methods of sound therapy in individuals with autism spectrum disorders. For this update, we searched the following databases in September 2010: CENTRAL (2010, Issue 2), MEDLINE (1950 to September week 2, 2010), EMBASE (1980 to Week 38, 2010), CINAHL (1937 to current), PsycINFO (1887 to current), ERIC (1966 to current), LILACS (September 2010) and the reference lists of published papers. One new study was found for inclusion. Randomised controlled trials involving adults or children with autism spectrum disorders. Treatment was auditory integration therapy or other sound therapies involving listening to music modified by filtering and modulation. Control groups could involve no treatment, a waiting list, usual therapy or a placebo equivalent. The outcomes were changes in core and associated features of autism spectrum disorders, auditory processing, quality of life and adverse events. Two independent review authors performed data extraction. All outcome data in the included papers were continuous. We calculated point estimates and standard errors from t-test scores and post-intervention means. Meta-analysis was inappropriate for the available data. We identified six randomised comtrolled trials of auditory integration therapy and one of Tomatis therapy, involving a total of 182 individuals aged three to 39 years. Two were cross-over trials. Five trials had fewer than 20 participants. Allocation concealment was inadequate for all studies. Twenty different outcome measures were used and only two outcomes were used by three or more studies. Meta-analysis was not possible due to very high heterogeneity or the presentation of data in unusable forms. Three studies (Bettison 1996; Zollweg 1997; Mudford 2000) did not demonstrate any benefit of auditory integration therapy over control conditions. Three studies (Veale 1993; Rimland 1995; Edelson 1999) reported improvements at three months for the auditory integration therapy group based on the Aberrant Behaviour Checklist, but they used a total score rather than subgroup scores, which is of questionable validity, and Veale's results did not reach statistical significance. Rimland 1995 also reported improvements at three months in the auditory integration therapy group for the Aberrant Behaviour Checklist subgroup scores. The study addressing Tomatis therapy (Corbett 2008) described an improvement in language with no difference between treatment and control conditions and did not report on the behavioural outcomes that were used in the auditory integration therapy trials. There is no evidence that auditory integration therapy or other sound therapies are effective as treatments for autism spectrum disorders. As synthesis of existing data has been limited by the disparate outcome measures used between studies, there is not sufficient evidence to prove that this treatment is not effective. However, of the seven studies including 182 participants that have been reported to date, only two (with an author in common), involving a total of 35 participants, report statistically significant improvements in the auditory intergration therapy group and for only two outcome measures (Aberrant Behaviour Checklist and Fisher's Auditory Problems Checklist). As such, there is no evidence to support the use of auditory integration therapy at this time. Source

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