The differential effect of socio-economic status, birth weight and gender on body mass index in Australian Aboriginal Children.

BACKGROUND: Adult Aboriginal Australians have 1.5-fold higher risk of obesity, but the trajectory of body mass index (BMI) through childhood and adolescence and the contribution of socio-economic factors remain unclear. Our objective was to determine the changes in BMI in Australian Aboriginal children relative to non-Aboriginal children as they move through adolescence into young adulthood, and to identify risk factors for higher BMI. METHODS: A prospective cohort study of Aboriginal and non-Aboriginal school children commenced in 2002 across 15 different screening areas across urban, regional and remote New South Wales, Australia. Socio-economic status was recorded at study enrolment and participants' BMI was measured every 2 years. We fitted a series of mixed linear regression models adjusting for age, birth weight and socio-economic status for boys and girls. RESULTS: In all, 3418 (1949 Aboriginal) participants were screened over a total of 11 387 participant years of follow-up. The prevalence of obesity was higher among Aboriginal children from mean age 11 years at baseline (11.6 vs 7.6%) to 16 years at 8 years follow-up (18.6 vs 12.3%). The mean BMI increased with age and was significantly higher among Aboriginal girls compared with non-Aboriginal girls (P<0.01). Girls born of low birth weight had a lower BMI than girls born of normal birth weight (P<0.001). Socio-economic status and low birth weight had a differential effect on BMI for Aboriginal boys compared with non-Aboriginal boys (P for interaction=0.01). Aboriginal boys of highest socio-economic status, unlike those of lower socio-economic status, had a higher BMI compared with non-Aboriginal boys. Non-Aboriginal boys of low birth weight were heavier than Aboriginal boys. CONCLUSIONS: Socio-economic status and birth weight have differential effects on BMI among Aboriginal boys, and Aboriginal girls had a higher mean BMI than non-Aboriginal girls through childhood and adolescence. Intervention programs need to recognise the differential risk for obesity for Aboriginal and non-Aboriginal boys and girls to maximise their impact.

Non-corticosteroid treatment for nephrotic syndrome in children.

BACKGROUND: Eighty to 90% of children with steroid-sensitive nephrotic syndrome (SSNS) have relapses. About half relapse frequently and are at risk of the adverse effects of corticosteroids. Non-corticosteroid immunosuppressive agents are used to prolong periods of remission in these children, however these agents have significant potential adverse effects. Currently there is no consensus as to the most appropriate second line agent in children who are steroid sensitive, but who continue to relapse. OBJECTIVES: To evaluate the benefits and harms of non-corticosteroid immunosuppressive agents in relapsing SSNS in children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, reference lists, conference abstracts and contact with known investigators. Search date: September 2007 SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs were included if they compared non-corticosteroid agents with placebo, prednisone or no treatment, different doses and/or durations of the same non-corticosteroid agent, different non-corticosteroid agents. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: We identified 26 studies (1173 children). Cyclophosphamide (RR 0.44, 95% CI 0.26 to 0.73) and chlorambucil (RR 0.15, 95% CI 0.02 to 0.95) significantly reduced the relapse risk at six to twelve months compared with prednisone alone. There was no difference in relapse risk at two years between chlorambucil and cyclophosphamide (RR 1.31, 95% CI 0.80 to 2.13). There was no 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) and levamisole (RR 0.43, 95% CI 0.27 to 0.68) was more effective than steroids alone but the effects were not sustained once treatment was stopped. There was no difference in the risk for relapse between mycophenolate mofetil and cyclosporin (RR 5.00, 95% CI 0.68 to 36.66) but CI were large. Mizoribine and azathioprine were no more effective than placebo or prednisone alone in maintaining remission. AUTHORS' CONCLUSIONS: 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. Clinically important differences in efficacy are possible and further comparative studies are still needed.

Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients.

BACKGROUND: 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. OBJECTIVES: To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause mortality in solid organ transplant recipients. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists and abstracts from conference proceedings without language restriction. Date of last search: February 2007 SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: Statistical analyses were performed using the random effects model and results expressed as relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). 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. MAIN RESULTS: Thirty four studies (3850 participants) were identified. 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. 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). Valganciclovir and IV ganciclovir were as effective as oral ganciclovir. AUTHORS' CONCLUSIONS: Prophylaxis with antiviral medications reduces CMV disease and CMV-associated mortality in solid organ transplant recipients. They should be used routinely in CMV positive recipients and in CMV negative recipients of CMV positive organ transplants.

Corticosteroid therapy for nephrotic syndrome in children.

BACKGROUND: In nephrotic syndrome (NS) protein leaks from the blood to the urine through the glomeruli resulting in hypoproteinaemia and generalised oedema. While the majority of children with NS respond to corticosteroids, 70% experience a relapsing course. Corticosteroids have reduced the mortality rate to around 3%. However corticosteroids have well recognised potentially serious adverse effects such as obesity, poor growth, hypertension, diabetes mellitus and osteoporosis. OBJECTIVES: To determine the benefits and harms of corticosteroid regimens in preventing relapse in children with steroid sensitive NS (SSNS). SEARCH STRATEGY: We searched CENTRAL, Cochrane Renal Group Specialised Register, MEDLINE and EMBASE without language restriction, reference lists of articles and contact with known investigators. Date of last search: December 2006 SELECTION CRITERIA: Randomised controlled trials performed in children (three months to 18 years) in their initial or subsequent episode of SSNS, comparing different durations, total doses or other dose strategies using any corticosteroid agent, with outcome data at six months or more. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Results were expressed as relative risk (RR) with 95% confidence intervals (CI) or mean difference (WMD). Meta-regression was used to explore potential between-study differences due to baseline risk of relapse, study quality and interventions. MAIN RESULTS: Twenty four trials were identified. Six trials comparing two months of prednisone or prednisolone with three months or more in the first episode showed longer duration significantly reduced the risk of relapse at 12 to 24 months (RR 0.70, 95% CI 0.58 to 0.84). There was an inverse linear relationship between treatment duration and risk of relapse (RR = 1.26 - 0.112 duration; P = 0.03). Four trials showed that six months of prednisone was more effective than three months in reducing the risk for relapse (RR 0.57; 95% CI 0.45 to 0.71). Deflazacort was significantly more effective in maintaining remission than prednisone in children who frequently relapsed in a single study (RR 0.44, 95% CI 0.25 to 0.78). There were no increases in adverse events. AUTHORS' CONCLUSIONS: Children in their first episode of SSNS should be treated for at least three months with an increase in benefit for up to seven months of treatment. For a baseline risk for relapse following the first episode of 60% with two months of therapy, daily prednisone or prednisolone given for four weeks followed by alternate-day therapy for six months would reduce the number of children relapsing by 33%.

Antibiotics for acute pyelonephritis in children.

BACKGROUND: Urinary tract infection (UTI) is one of the most common bacterial infection in infants. The most severe form of UTI is acute pyelonephritis, which results in significant acute morbidity and may cause permanent renal damage. Published guidelines recommend treatment of acute pyelonephritis initially with intravenous (IV) therapy followed by oral therapy for seven to 14 days though there is no consensus on the duration of either IV or oral therapy. OBJECTIVES: To determine the benefits and harms of different antibiotic regimens for the treatment of acute pyelonephritis in children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, reference lists of articles and conference proceedings without language restriction. Date of most recent search: December 2006. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing different antibiotic agents, routes, frequencies or durations of therapy in children aged 0 to 18 years with proven UTI and acute pyelonephritis were selected. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes or mean difference (WMD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS: Twenty three studies (3295 children) were eligible for inclusion. No significant differences were found in persistent renal damage at 6 months (2 studies, 424 children: RR 0.87, 95% CI 0.35 to 2.16) or in duration of fever (2 studies, 693 children: WMD 1.54, 95% CI -1.67 to 4.76) between oral antibiotic therapy (10 to 14 days) and IV therapy (3 days) followed by oral therapy (10 days). Similarly no significant differences in persistent renal damage (3 studies, 341 children: RR 1.13, 95% CI 0.86 to 1.49) were found between IV therapy (3 to 4 days) followed by oral therapy and IV therapy for 7 to 14 days. No significant differences in efficacy were found between daily and thrice daily administration of aminoglycosides (1 study, 179 children, persistent symptoms at 3 days: RR 1.98, 95% CI 0.37 to 10.53). AUTHORS' CONCLUSIONS: These results suggest that children with acute pyelonephritis can be treated effectively with oral antibiotics (cefixime, ceftibuten and amoxycillin/clavulanic acid) or with short courses (2 to 4 days) of IV therapy followed by oral therapy. If IV therapy is chosen, single daily dosing with aminoglycosides is safe and effective. Studies are required to determine the optimal total duration of therapy.

Interventions for primary vesicoureteric reflux.

BACKGROUND: Vesicoureteric reflux (VUR) results in urine passing, in a retrograde manner, up the ureter. Urinary tract infections (UTIs) have been considered the main cause of permanent renal parenchymal damage in children with reflux. Management of these children has been directed at preventing infection by antibiotic prophylaxis and/or surgical correction of reflux. Controversy remains as to the optimum strategies. OBJECTIVES: To evaluate the benefits and harms of different treatment options for primary VUR. SEARCH STRATEGY: Randomised controlled trials (RCTs) were identified from the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists of articles and abstracts from conference proceedings. Date of last search: June 2006 SELECTION CRITERIA: Any treatment of VUR including surgery, antibiotic prophylaxis of any duration, non-invasive techniques and any combination of therapies. DATA COLLECTION AND ANALYSIS: Two authors independently searched the literature, determined study eligibility, assessed quality, extracted and entered data. For dichotomous outcomes, results were expressed as relative risk (RR) and 95% confidence intervals (CI). Data were pooled using the random effects model. MAIN RESULTS: Eleven studies (1148 children) were identified. Seven compared correction of VUR (by surgery or endoscope) plus antibiotics for 1-24 months with antibiotics alone, two compared antibiotics with no treatment and two compared different materials for endoscopic correction of VUR. Risk of UTI by 2, 5 and 10 years was not significantly different between surgical and medical groups (2 years RR 1.07, 95% CI 0.32 to 2.09; 5 years RR 0.99, 95% CI 0.79 to 1.26; 10 years RR 1.06, 95% CI 0.78 to 1.44). Combined treatment resulted in a 50% reduction in febrile UTI by 10 years (RR 0.54, 95% CI 0.55 to 0.92) but no concomitant reduction in risk of new or progressive renal damage by 10 years (RR 1.03, 95% CI 0.53 to 2.00). In two small studies no significant differences in risk for UTI (RR 0.75, 95% CI 0.15 to 3.84) or renal damage (RR 1.70, 95% CI 0.36 to 8.07) were found between antibiotic prophylaxis and no treatment. AUTHORS' CONCLUSIONS: It is uncertain whether the treatment of children with VUR confers clinically important benefit. The additional benefit of surgery over antibiotics alone is small at best. Assuming a UTI rate of 20% for children with VUR on antibiotics for five years, nine reimplantations would be required to prevent one febrile UTI, with no reduction in the number of children developing any UTI or renal damage.

Immunoglobulins, vaccines or interferon for preventing cytomegalovirus disease in solid organ transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is the most common virus causing disease and death in solid organ transplant recipients during the first six months post-transplant. Previous systematic reviews have demonstrated the efficacy of antiviral medications used prophylactically or pre-emptively in preventing CMV disease. In this review the efficacy of older agents (immunoglobulins (IgG), anti CMV vaccines and interferon) are examined. OBJECTIVES: To assess the benefits and harms of IgG, anti CMV vaccines or interferon for preventing symptomatic CMV disease in solid organ transplant recipients. SEARCH STRATEGY: We searched the Cochrane Renal Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE, EMBASE, reference lists and abstracts from conference proceedings without language restriction. Date of last search: December 2005 SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing IgG, anti CMV vaccine or interferon with placebo or no treatment, IgG alone or combined with antiviral medications with antiviral medications or IgG alone in recipients of any solid organ transplant. DATA COLLECTION AND ANALYSIS: Two of four authors independently assessed trial quality and extracted data from each trial. Statistical analyses were performed using the random effects model and results expressed as relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). MAIN RESULTS: Thirty seven trials (2185 participants) were included in this review. There was no significant difference in the risk for CMV disease (16 trials, 770 patients: RR 0.80, 95% CI 0.61 to 1.05), CMV infection (14 trials, 775 patients: RR 0.94, 95% CI 0.80 to 1.10) or all-cause mortality (8 trials, 502 patients: RR 0.57, 95% CI 0.32 to 1.03) with IgG compared with placebo/no treatment. However IgG significantly reduced the risk of death from CMV disease (6 trials, 346 patients: RR 0.33, 95% CI 0.14 to 0.80). There was no difference in the risk for CMV disease (4 trials, 298 patients: RR 1.17, 95% CI 0.74 to 1.86), CMV infection (4 trials, 298 patients: RR 1.16, 95% CI 0.89 to 1.52) or all-cause mortality (2 trials, 217 patients: RR 0.92, 95% CI 0.37 to 2.29) between antiviral medication combined with IgG and antiviral medication alone. There was no significant difference in the risk of CMV disease with anti CMV vaccine or interferon compared with placebo or no treatment. AUTHORS' CONCLUSIONS: Currently there are no indications for IgG in the prophylaxis of CMV disease in recipients of solid organ transplants.

Interventions for idiopathic steroid-resistant nephrotic syndrome in children.

BACKGROUND: The majority of children who present with their first episode of nephrotic syndrome, achieve remission with corticosteroid therapy. Children who fail to respond may be treated with immunosuppressive agents such as cyclophosphamide, chlorambucil or cyclosporin, or with non-immunosuppressive agents such as ACE inhibitors. Optimal combinations of these agents with the least toxicity remain to be determined. OBJECTIVES: To evaluate the benefits and harms of interventions used to treat idiopathic steroid resistant nephrotic syndrome (SRNS) in children. SEARCH STRATEGY: Randomised controlled trials (RCTs) were identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, reference lists of articles and abstracts from conference proceedings. Date of most recent search: June 2005 SELECTION CRITERIA: RCTs and quasi-RCTs were included if they compared different immunosuppressive agents or non-immunosuppressive agents with placebo, prednisone or other agent given orally or parenterally in children aged three months to 18 years with SRNS. DATA COLLECTION AND ANALYSIS: Two reviewers independently searched the literature, determined trial eligibility, assessed quality, extracted data and entered it in RevMan. For dichotomous outcomes, results were expressed as relative risk (RR) and 95% confidence intervals (CI). Data were pooled using the random effects model. MAIN RESULTS: Eleven RCTs (312 children) were included. Cyclosporin when compared with placebo or no treatment significantly increased the number of children who achieved complete remission (three trials, 49 children: RR for persistent nephrotic syndrome 0.64, 95% CI, 0.47 to 0.88). There was no significant difference in the number of children who achieved complete remission between oral cyclophosphamide with prednisone and prednisone alone (two trials, 91 children: RR 1.01, 95% CI 0.74 to 1.36), between intravenous cyclophosphamide and oral cyclophosphamide (one study, 11 children: RR 0.09, 95% CI 0.01 to 1.39) and between azathioprine with prednisone and prednisone alone (one trial 31 children: RR 1.01, 95% CI 0.77 to 1.32). ACE inhibitors significantly reduced proteinuria (two trials, 70 children). After 12 weeks of treatment fosinopril reduced proteinuria by 0.95 g/24 h (95% CI -1.21 to -0.69). No RCTs were identified comparing combination regimens comprising high dose steroids, alkylating agents or cyclosporin with single agents, placebo or no treatment. AUTHORS' CONCLUSIONS: Further adequately powered and well designed RCTs are needed to confirm the efficacy of cyclosporin and to evaluate other regimens for idiopathic SRNS including high dose steroids with alkylating agents or cyclosporin.

Pre-emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus disease in solid organ transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients. Pre-emptive treatment with antiviral agents of patients with CMV viraemia has been widely adopted as an alternative to routine prophylaxis to prevent CMV disease. OBJECTIVES: This review was conducted to evaluate the efficacy of pre-emptive treatment in preventing symptomatic CMV disease. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library Issue 2, 2005), MEDLINE (1966 to February 2005), EMBASE (1980 to February 2005) and reference lists and conference proceedings were searched. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of pre-emptive treatment versus placebo, no treatment or antiviral prophylaxis in solid organ transplant recipients. DATA COLLECTION AND ANALYSIS: Two authors assessed the quality and extracted all data. Analysis was with a random-effects model and results expressed as relative risk (RR) and 95% confidence intervals (CI). MAIN RESULTS: Ten eligible trials (476 patients) were identified, six of pre-emptive treatment versus placebo or treatment of CMV when disease occurred (standard care), three of pre-emptive treatment versus antiviral prophylaxis and one of oral versus intravenous pre-emptive treatment. Compared with placebo or standard care, pre-emptive treatment significantly reduced the risk of CMV disease (six trials, 288 patients: RR 0.29, 95% CI 0.11 to 0.80) but not acute rejection (three trials, 185 patient: RR 1.06, 95% CI 0.64 to 1.76) or all-cause mortality (two trials, 176 patients: RR 1.23, 95% CI 0.35 to 4.30). Comparative trials of pre-emptive therapy versus prophylaxis showed no significant difference in the risks of CMV disease, acute rejection or all-cause mortality. AUTHORS' CONCLUSIONS: Few RCTs have evaluated the effects of pre-emptive therapy to prevent CMV disease. Pre-emptive therapy is effective compared with placebo or standard care, but additional head-to-head trials are required to determine the relative benefits and harms of pre-emptive therapy and prophylaxis to prevent CMV disease in solid organ transplant recipients.

Growth hormone for children with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is an uncommon but important condition. Growth retardation, one of the complications of CKD, is of concern to families. Recombinant human growth hormone (rhGH) treatment has been used to help short children with CKD attain a height more in keeping with their age group. However, there are concerns that rhGH may have an adverse effect on the preservation of native kidney function, predispose to acute rejection in kidney transplant recipients, and cause benign intracranial hypertension and slipped capital femoral epiphysis. OBJECTIVES: To evaluate the benefits and harms of rhGH treatment in children with CKD. SEARCH STRATEGY: Randomised controlled trials (RCTs) were identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, article reference lists and through contact with local and international experts in the field. Date of most recent search: July 2005 SELECTION CRITERIA: RCTs were included if they were carried out in children aged 0-18 years, diagnosed with CKD, who were pre-dialysis, on dialysis or post-transplant; if they compared rhGH treatment with placebo/no treatment or two doses of rhGH treatments; and if they included height outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for methodological quality and extracted data from eligible trials. Data was pooled using a random effects model with calculation of weighted mean difference (MD) for continuous outcomes and relative risk (RR) for categorical outcomes with 95% confidence intervals (CI). MAIN RESULTS: Fifteen RCTs (629 children) were identified. Treatment with rhGH (28 IU/m(2)/wk) resulted in a significant increase in height standard deviation score (SDS) at one year (MD 0.78 SDS, 95% CI 0.52 to 1.04), and a significant increase in height velocity at six months (MD 2.85 cm/6 mo, 95%CI 2.22 to 3.48) and one year (MD 3.80 cm/y, 95%CI 3.20 to 4.39). Compared to the 14 IU/m(2)/wk group, there was a 1.34 cm/y (0.55 to 2.13) increase in height velocity in the 28 IU/m(2)/wk group. The frequency of reported side effects of rhGH were similar to that of the control group. AUTHORS' CONCLUSIONS: One year of 28 IU/m(2)/wk rhGH in children with CKD resulted in a 3.80 cm/y increase in height velocity above that of untreated patients. Trials were too short to determine if continuing treatment resulted in an increase in final adult height.

Antibiotics for acute pyelonephritis in children.

BACKGROUND: Urinary tract infection (UTI) is one of the most common bacterial infection in infants. The most severe form of UTI is acute pyelonephritis, which results in significant acute morbidity and may cause permanent renal damage. Published guidelines recommend treatment of acute pyelonephritis initially with intravenous (IV) therapy followed by oral therapy for seven to 14 days though there is no consensus on the duration of either IV or oral therapy. OBJECTIVES: To determine the benefits and harms of different antibiotic regimens for the treatment of acute pyelonephritis in children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists of articles and abstracts from conference proceedings without language restriction. Date of most recent search: June 2004. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing different antibiotic agents, routes, frequencies or durations of therapy in children aged 0 to 18 years with proven UTI and acute pyelonephritis were selected. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes or weight mean difference (WMD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS: Eighteen trials (2612 children) were eligible for inclusion. No significant differences were found in persistent renal damage at six months (one trial, 306 infants: RR 1.45, 95% CI 0.69 to 3.03) or in duration of fever (WMD 0.80, 95% CI -4.41 to - 6.01) between oral cefixime therapy (14 days) and IV therapy (three days) followed by oral therapy (10 days). Similarly no significant differences in persistent renal damage (three trials, 315 children: RR 0.99, 95% CI 0.72 to 1.37) were found between IV therapy (3-4 days) followed by oral therapy and IV therapy for 7-14 days. In addition no significant differences in efficacy were found between daily and thrice daily administration of aminoglycosides (one trial, 179 children, persistent symptoms at three days: RR 1.98, 95% CI 0.37 to 10.53). AUTHORS' CONCLUSIONS: These results suggest that children with acute pyelonephritis can be treated effectively with oral cefixime or with short courses (2-4 days) of IV therapy followed by oral therapy. If IV therapy is chosen, single daily dosing with aminoglycosides is safe and effective. Trials are required to determine the optimal total duration of therapy and if other oral antibiotics can be used in the initial treatment of acute pyelonephritis.

Non-corticosteroid treatment for nephrotic syndrome in children.

BACKGROUND: Eighty to ninety per cent of children with steroid-sensitive nephrotic syndrome (SSNS) have relapses. About half relapse frequently and are at risk of the adverse effects of corticosteroids. Non-corticosteroid immunosuppressive agents are used to prolong periods of remission in children who relapse frequently. However these non-corticosteroid agents also have significant potential adverse effects. Currently there is no consensus as to the most appropriate second line agent in children who are steroid sensitive, but who continue to relapse. OBJECTIVES: To evaluate the benefits and harms of non-corticosteroid immunosuppressive agents in relapsing SSNS in children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, reference lists of articles, abstracts from proceedings and contact with known investigators. Search date: August 2004 SELECTION CRITERIA: RCTs or quasi-RCTs were included if they were undertaken in children with relapsing SSNS, if they compared non-corticosteroid agents with placebo, prednisone or no treatment, different doses and/or durations of the same non-corticosteroid agent, different non-corticosteroid agents and outcome data at six months. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: Twenty trials involving 923 children were identified. Cyclophosphamide (three trials: RR 0.44, 95% CI 0.26 to 0.73) and chlorambucil (two trials: RR 0.13, 95% CI 0.03 to 0.57) significantly reduced the relapse risk at six to twelve months compared with prednisone alone. In the single chlorambucil versus cyclophosphamide trial, there was no observed difference in relapse risk at two years (RR 1.31, 95% CI 0.80 to 2.13). Cyclosporin was as effective as cyclophosphamide (one trial: RR 1.07, 95% CI 0.48 to 2.35) and chlorambucil (one trial: RR 0.82, 95% CI 0.44 to 1.53) but the effect was not sustained when cyclosporin was ceased. During treatment, levamisole (three trials: RR 0.60, 95% CI 0.45 to 0.79) was more effective than steroids alone but the effect was not sustained. Mizoribine (one trial) and azathioprine (two trials) were no more effective than placebo or prednisone alone in maintaining remission. AUTHORS' CONCLUSIONS: 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. Clinically important differences in efficacy among these agents are possible and further comparative trials are still needed.

Corticosteroid therapy for nephrotic syndrome in children.

BACKGROUND: In nephrotic syndrome protein leaks from the blood to the urine through the glomeruli resulting in hypoproteinaemia and generalised oedema. While the majority of children with nephrotic syndrome respond to corticosteroids, 70% experience a relapsing course. Corticosteroid usage has reduced the mortality rate to around 3%, however they have known serious adverse effects. OBJECTIVES: To determine the benefits and harms of corticosteroid regimens in preventing relapse in children with steroid sensitive nephrotic syndrome (SSNS). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Renal Group Specialised Register, MEDLINE and EMBASE without language restriction, reference lists of articles, abstracts from conference proceedings and contact with known investigators. Date of most recent search: October 2004 SELECTION CRITERIA: Randomised controlled trials performed in children (three months to 18 years) in their initial or subsequent episode of SSNS, comparing different durations, total doses or other dose strategies using any corticosteroid agent, with outcome data at six months or more. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as relative risk (RR) with 95% confidence intervals (CI).Meta-regression was used to explore potential between-study differences due to baseline risk of relapse, study quality and interventions. MAIN RESULTS: Nineteen trials were identified. Six trials comparing two months of prednisone with three months or more in the first episode showed longer duration significantly reduced the risk of relapse at 12 to 24 months (RR 0.70; 95% CI 0.58 to 0.84). There was an inverse linear relationship between treatment duration and risk of relapse (RR = 1.26 - 0.112 duration; P = 0.03). There was a significant reduction in the number of frequent relapsers and the mean relapse rate/patient/year. Deflazacort was significantly more effective in maintaining remission than prednisone in children who frequently relapsed (RR 0.44; 95% CI 0.25 to 0.78). There were no increases in adverse events. AUTHORS' CONCLUSIONS: Children in their first episode of SSNS should be treated for at least three months with an increase in benefit being demonstrated for up to seven months of treatment For a baseline risk for relapse following the first episode of 60% with two months of prednisone, daily prednisone for four weeks followed by alternate-day therapy for six months would reduce the number of children relapsing by 33%. Deflazacort deserves further study for frequent relapsers.

Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients.

BACKGROUND: 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. OBJECTIVES: To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause mortality in solid organ transplant recipients. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists and abstracts from conference proceedings without language restriction. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing antiviral medications with placebo or no treatment, trials comparing different antiviral medications and trials comparing different regimens of the same antiviral medications in recipients of any solid organ transplant. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data from each trial. Statistical analyses were performed using the random effects model and results expressed as relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). 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. MAIN RESULTS: Thirty two trials (3737 participants) were identified. Prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment significantly reduced the risk for CMV disease (19 trials; RR 0.42, 95% CI 0.34 to 0.52), CMV infection (17 trials; RR 0.61, 95% CI 0.48 to 0.77), and all-cause mortality (17 trials; RR 0.63, 95% CI 0.43 to 0.92) primarily due to reduced mortality from CMV disease (seven trials; 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 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. In direct comparison trials, ganciclovir was more effective than aciclovir in preventing CMV disease (seven trials; RR 0.37, 95% Cl 0.23 to 0.60). Valganciclovir and intravenous ganciclovir were as effective as oral ganciclovir. AUTHORS' CONCLUSIONS: Prophylaxis with antiviral medications reduces CMV disease and CMV-associated mortality in solid organ transplant recipients. They should be used routinely in CMV positive recipients and in CMV negative recipients of CMV positive organ transplants.

Renal transplantation in children ages 1 to 5 years.

Renal transplantation was carried out in 21 children ages 1 to 5 years. Eighteen received grafts from a living, related donor (LRD). Four children died, one following rejection, and three because of infection. Five children lost their initial grafts and two have received new transplants. Cumulative patient survival two and four years following LRD transplantation was 94% and 76%, respectively. This was similar to results found in children ages 6 to 14 years. Accelerated growth rates were seen in the first posttransplant year in those small children who were severely growth-retarded at the same time of transplantation and who achieved normal graft function. However, only one of these children ultimately reached the tenth percentile for height for chronological age. We conclude that renal transplantation is warranted in the very young child with renal failure.

Abnormal cortical appearances in pediatric renal allografts.

Renal cortical studies were performed in 19 children with renal transplants. There were 10 normal studies and 9 abnormal studies, 8 of which showed multiple large focal peripheral cortical defects. The following factors showed a positive correlation: (a) the ischemia time of the transplant kidney was significantly shorter in patients with normal studies; (b) cadaver grafts were more likely to have abnormal scan appearances than living related donor grafts; and (c) in four of the five patients with double renal arteries, the scans were abnormal in multiple sites. A possible pathophysiologic mechanism to explain these scan appearances is asymptomatic segmental graft infarction secondary to progressive vascular disease. These infarcts may be a long-term sequela of ischemic insult at the time of or prior to the insertion of the renal allograft.

Volume expanded diuretic renography in the postnatal assessment of suspected uretero-pelvic junction obstruction.

Controversy surrounds the role of 99mTc-diethylenetriamine pentaacetic acid renography in suspected uretero-pelvic junction obstruction in early life. Accordingly, we retrospectively reviewed 18 patients (28 hydronephrotic kidneys) with a mean age of 2 mo (range: 1 wk-6 mo) who underwent a total of 36 scans using intravenous volume expansion (10 ml/kg) and furosemide diuresis (1 mg/kg). Initial scans were classified as obstructed, not obstructed or indeterminate using differential renal function, furosemide washout T 1/2 and visual assessment of tracer clearance. Those initially classified as obstructed (n = 8) have been surgically confirmed. In the indeterminate (n = 6) and nonobstructed (n = 14) groups, three and two kidneys, respectively, developed obstruction on progress scans. Mean follow-up in the nonsurgical patients was approximately 9 mo (range: 4-17 mo). A total of 13 kidneys had developed obstruction by renographic criteria, and to date 12 have surgical confirmation. Our data indicate that: (1) scans classified as obstructed correlate well with surgery; (2) an initial classification of indeterminate or nonobstructed does not exclude later development of obstruction; and (3) serial scans correctly stratify children with possible uretero-pelvic junction obstruction.

Age-related differences in susceptibility of males and females to end-stage reflux nephropathy.

Age-specific rates for entry into Australian maintenance dialysis and transplantation programmes show that reflux nephropathy is equally common as a cause of end-stage renal failure in males and females from 5 to 24 years, and over 75 years of age, but between 35 and 64 years renal failure due to this disease is significantly more common in women than men.

Treatment of childhood renal osteodystrophy with calcitriol or ergocalciferol.

Quantitative bone histology, biochemistry and height velocities were studied in 18 children suffering from chronic renal failure. Eight received calcitriol, 7 ergocalciferol and 3, though alloted to a treatment group, failed to comply with therapy. A histochemical stain for aluminum showed heavy deposition at the calcification front in 3 patients; 2, in the calcitriol group had severe osteomalacia which worsened during treatment, and 1 in the ergocalciferol group had osteomalacia which did not improve. One had never undergone hemodialysis. Bone histology improved markedly in the remaining 12 patients, whichever vitamin D preparation was used; it was unchanged in 3 non-compliant children. Plasma calcium levels rose while parathyroid hormone and alkaline phosphatase levels fell following both treatments, and were unchanged in non-compliant children. Hypercalcemia occurred more frequently following calcitriol therapy (11 episodes) than following ergocalciferol therapy (3 episodes). Height velocities, studied in 11 children, increased in 5 (3 on ergocalciferol and 2 on calcitriol) and were unchanged in 6 (1 on ergocalciferol, 5 on calcitriol). Improved bone histology did not correlate with increase in height velocity. As ergocalciferol and calcitriol had similar therapeutic effects and as side-effects were more common with calcitriol, it is concluded that calcitriol provides no advantage over ergocalciferol in the treatment of renal bone disease in children.

The diagnosis of renal osteodystrophy: a comparison of Technetium-99m-pyrophosphate bone scintigraphy with other techniques.

In order to determine the place of Technetium-99m-pyrophosphate bone scintigraphy in the assessment of renal osteodystrophy, 17 patients with chronic renal failure requiring hemodialysis underwent bone scans and these were compared to results of biochemical, radiological and histologic studies. Bone histology was abnormal in all patients with most having evidence of osteomalacia and hyperparathyroid bone disease. Using semi-quantitative scan scores and regional bone-standard ratios, isotope uptake was increased in 16 patients, while 15 had elevated alkaline phosphatase levels and 7 had X-ray changes. An osteoid-osteoclast index combining histological osteomalacia and hyperparathyroid disease was derived and was found to correlate more closely with alkaline phosphatase and parathyroid hormone levels than with scan parameters. It was concluded that bone scans did not provide therapeutically useful information that could not be obtained from biochemical and radiological studies. It appeared that only bone histology could differentiate osteomalacia and hyperparathyroid bone disease.