Long term tapering versus standard prednisolone treatment for first episode of childhood nephrotic syndrome: phase III randomised controlled trial and economic evaluation.

OBJECTIVE: To determine whether extending initial prednisolone treatment from eight to 16 weeks in children with idiopathic steroid sensitive nephrotic syndrome improves the pattern of disease relapse. DESIGN: Double blind, parallel group, phase III randomised placebo controlled trial, including a cost effectiveness analysis. SETTING: 125 UK National Health Service district general hospitals and tertiary paediatric nephrology centres. PARTICIPANTS: 237 children aged 1-14 years with a first episode of steroid sensitive nephrotic syndrome. INTERVENTIONS: Children were randomised to receive an extended 16 week course of prednisolone (total dose 3150 mg/m2) or a standard eight week course of prednisolone (total dose 2240 mg/m2). The drug was supplied as 5 mg tablets alongside matching placebo so that participants in both groups received the same number of tablets at any time point in the study. A minimisation algorithm ensured balanced treatment allocation by ethnicity (South Asian, white, or other) and age (5 years or less, 6 years or more). MAIN OUTCOME MEASURES: The primary outcome measure was time to first relapse over a minimum follow-up of 24 months. Secondary outcome measures were relapse rate, incidence of frequently relapsing nephrotic syndrome and steroid dependent nephrotic syndrome, use of alternative immunosuppressive treatment, rates of adverse events, behavioural change using the Achenbach child behaviour checklist, quality adjusted life years, and cost effectiveness from a healthcare perspective. Analysis was by intention to treat. RESULTS: No significant difference was found in time to first relapse (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17, log rank P=0.28) or in the incidence of frequently relapsing nephrotic syndrome (extended course 60/114 (53%) v standard course 55/109 (50%), P=0.75), steroid dependent nephrotic syndrome (48/114 (42%) v 48/109 (44%), P=0.77), or requirement for alternative immunosuppressive treatment (62/114 (54%) v 61/109 (56%), P=0.81). Total prednisolone dose after completion of the trial drug was 6674 mg for the extended course versus 5475 mg for the standard course (P=0.07). There were no statistically significant differences in serious adverse event rates (extended course 19/114 (17%) v standard course 27/109 (25%), P=0.13) or adverse event rates, with the exception of behaviour, which was poorer in the standard course group. Scores on the Achenbach child behaviour checklist did not, however, differ. Extended course treatment was associated with a mean increase in generic quality of life (0.0162 additional quality adjusted life years, 95% confidence interval -0.005 to 0.037) and cost savings (difference -£1673 ($2160; €1930), 95% confidence interval -£3455 to £109). CONCLUSIONS: Clinical outcomes did not improve when the initial course of prednisolone treatment was extended from eight to 16 weeks in UK children with steroid sensitive nephrotic syndrome. However, evidence was found of a short term health economic benefit through reduced resource use and increased quality of life. TRIAL REGISTRATION: ISRCTN16645249; EudraCT 2010-022489-29.

Socioeconomics of Administering Rituximab for Nephrotic Syndrome.

Nephrotic syndrome is a type of intractable disease caused by a disorder in the kidneys, which produces swelling. Although some patients show rapid improvement and recover completely with conventional treatment, many others experience frequent recurrence (frequently relapsing nephrotic syndrome) while some remain dependent on the same high dose of steroids they were initially prescribed at the start of treatment (steroid-dependent nephrotic syndrome). In the latter cases, side effects of prolonged steroid use are a major issue. Some reports show that administering rituximab is effective in treating patients with steroid resistance. However, drugs like rituximab, directed at specific molecular targets, are generally expensive and therefore need to be evaluated from a health economics perspective before being approved for widespread use. The research team compared the number of relapses and total medical costs in the 24-month period before and the same period after patients took rituximab. We found that relapse decreased from a mean of 4.30 (±2.76) times to 0.27 (±0.52) times, and the total medical costs shrank from USD 2,923 to 1,280 per month (mainly the result of lower inpatient costs). The study also identified a correlation between lower urinary protein levels and a reduction in total medical costs. Rituximab, therefore, proved beneficial in both clinical and cost-effective terms. While rising healthcare costs are becoming a major social problem, we should expect that the development of new drugs with high cost performance will be encouraged from the vantage of socioeconomics.

Economic evaluation of human albumin use in patients with nephrotic syndrome in four Brazilian public hospitals: pharmacoeconomic study.

CONTEXT AND OBJECTIVE:: In 2004, the Brazilian National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária, ANVISA) published a resolution establishing guidelines for albumin use. Although the published data do not indicate any definitive conclusions about the benefits of albumin use in patients with nephrotic syndrome (NS), the guidelines recommend this procedure only in cases of edema that is refractory to use of diuretics. The aim here was to analyze albumin use among patients with nephrotic syndrome. DESIGN AND SETTING:: Pharmacoeconomic study conducted in four large public referral hospitals for nephrology services in northeastern Brazil. METHOD:: Cost-effectiveness and cost-utility economic evaluations were performed on a concurrent cohort of patients with nephrotic syndrome, who were divided into two groups according to compliance or noncompliance with the guidelines. Quality-of-life data were obtained from the SF36 and CHQ-PF50 questionnaires. RESULTS:: This study enrolled 109 patients (60% adults and 56% women); 41.3% were using albumin in accordance with the guidelines. The weight, diuresis and fluid balance parameters were more cost-effective for patients who adhered to the guidelines. Regarding days of hospitalization avoided, the incremental ratio showed a daily cost of R$ 55.33, and guideline-compliant patients were hospitalized for five days or fewer. The quality of life improved by 8%, and savings of R$ 3,458.13/QALY (quality-adjusted life year) for the healthcare system were generated through guideline compliance. CONCLUSION:: The economic analyses of this study demonstrated that there were greater cost benefits for patients whose treatment followed the guidelines.

Economic evaluation of human albumin use in patients with nephrotic syndrome in four Brazilian public hospitals: pharmacoeconomic study / Avaliação econômica do uso de albumina humana em pacientes com síndrome nefrótica em quatro hospitais públicos brasileiros: estudo de farmacoeconomia

ABSTRACT CONTEXT AND OBJECTIVE: In 2004, the Brazilian National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária, ANVISA) published a resolution establishing guidelines for albumin use. Although the published data do not indicate any definitive conclusions about the benefits of albumin use in patients with nephrotic syndrome (NS), the guidelines recommend this procedure only in cases of edema that is refractory to use of diuretics. The aim here was to analyze albumin use among patients with nephrotic syndrome. DESIGN AND SETTING: Pharmacoeconomic study conducted in four large public referral hospitals for nephrology services in northeastern Brazil. METHOD: Cost-effectiveness and cost-utility economic evaluations were performed on a concurrent cohort of patients with nephrotic syndrome, who were divided into two groups according to compliance or noncompliance with the guidelines. Quality-of-life data were obtained from the SF36 and CHQ-PF50 questionnaires. RESULTS: This study enrolled 109 patients (60% adults and 56% women); 41.3% were using albumin in accordance with the guidelines. The weight, diuresis and fluid balance parameters were more cost-effective for patients who adhered to the guidelines. Regarding days of hospitalization avoided, the incremental ratio showed a daily cost of R$ 55.33, and guideline-compliant patients were hospitalized for five days or fewer. The quality of life improved by 8%, and savings of R$ 3,458.13/QALY (quality-adjusted life year) for the healthcare system were generated through guideline compliance. CONCLUSION: The economic analyses of this study demonstrated that there were greater cost benefits for patients whose treatment followed the guidelines.

RESUMO CONTEXTO E OBJETIVO: Em 2004, a Agência Nacional de Vigilância Sanitária (ANVISA) publicou uma resolução que estabelece diretrizes para o uso de albumina. Embora os dados publicados não indiquem conclusões definitivas sobre os benefícios do uso de albumina em pacientes com síndrome nefrótica (SN), a diretriz recomenda o procedimento apenas em casos de edema refratário ao uso de diuréticos. O objetivo aqui foi analisar o uso de albumina em pacientes com síndrome nefrótica. TIPO DE ESTUDO E LOCAL: Estudo farmacoeconômico realizado em quatro grandes hospitais públicos de referência em serviços de nefrologia no nordeste do Brasil. MÉTODO: Foram realizadas avaliações econômicas do tipo custo-efetividade e custo-utilidade em uma coorte concorrente de pacientes com síndrome nefrótica, divididos em dois grupos de acordo com o cumprimento ou descumprimento das diretrizes. Dados de qualidade de vida foram obtidos a partir dos questionários SF36 e CHQ-PF50. RESULTADOS: Este estudo incluiu 109 pacientes (60% adultos e 56% mulheres); 41,3% estavam usando albumina conforme as diretrizes. Os parâmetros de peso, diurese e balanço hídrico foram mais custo-efetivos para pacientes que aderiram às diretrizes. Quanto a dias de internação evitados, a razão incremental mostrou um custo diário de R$ 55,33, sendo que os pacientes que seguiram as diretrizes ficaram cinco dias a menos internados. A qualidade de vida melhorou 8%, gerando economia de R$ 3,458.13/QALY (quality-adjusted life year) para o sistema de saúde por meio do cumprimento das diretrizes. CONCLUSÃO: As análises econômicas deste estudo demonstraram maiores benefícios em termos de custo para os pacientes cujo tratamento seguiu as diretrizes.

Influence of the New Cooperative Medical Scheme on hospitalization cost of patients with nephrotic syndrome in rural China.

INTRODUCTION: Rural residents are benefitting from the current New Cooperative Medical Scheme (NCMS) in China. Treatment of diseases has improved and the total cost of hospitalization has decreased significantly because of the application of NCMS. Most articles in this area have mainly focused on the policy of NCMS, but few studies have been relevant to the influence of NCMS on a specific disease and the cost. In the present study, the impact of NCMS on hospitalization costs of patient with nephrotic syndrome from the countryside was investigated and discussed. METHODS: Three hundred and ninety patients from China and with nephrotic syndrome were enrolled into the present study and were divided into two groups according to whether they had joined the NCMS. The total hospitalization cost, check cost (such as laboratory testing and ultrasound), drugs cost, length of stay in hospital and ratio of renal biopsy in all patients were analyzed. RESULTS: The expenses for individuals decreased significantly in patients who were part of the NCMS, in contrast with the patients without the NCMS (p<0.001). The ratio of renal biopsy increased significantly in patients who were part of the NCMS (p<0.01). There was no significant difference in cost and length of stay between the two groups. CONCLUSIONS: The NCMS contributes to reducing personal expenses and therapy of disease.

Short course daily prednisolone therapy during an upper respiratory tract infection in children with relapsing steroid-sensitive nephrotic syndrome (PREDNOS 2): protocol for a randomised controlled trial.

BACKGROUND: Relapses of childhood steroid-sensitive nephrotic syndrome (SSNS) are treated with a 4- to 8-week course of high-dose oral prednisolone, which may be associated with significant adverse effects. There is a clear association between upper respiratory tract infection (URTI) and relapse development. Previous studies in developing nations have suggested that introducing a 5- to 7-day course of daily prednisolone during an URTI may prevent a relapse developing and the need for a treatment course of high-dose prednisolone. The aim of PREDNOS 2 is to evaluate the effectiveness of a 6-day course of daily prednisolone therapy during an URTI in reducing the development of a subsequent relapse in a developed nation. METHODS/DESIGN: The subjects will be 300 children with relapsing SSNS (≥2 relapses in preceding year), who will be randomised to receive either a 6-day course of daily prednisolone or no change to their current therapy (with the use of placebo to double blind) each time they develop an URTI over 12 months. A strict definition for URTI will be used. Subjects will be reviewed at 3, 6, 9 and 12 months to capture data regarding relapse history, ongoing therapy and adverse effect profile, including behavioural problems and quality of life. A formal health economic analysis will also be performed. The primary end point of the study will be the incidence of URTI-related relapse (3 days of Albustix +++) following the first infection during the 12-month follow-up period. DNA and RNA samples will be collected to identify a potential genetic cause for the disease. Subjects will be recruited from over 100 UK centres with the assistance of the Medicines for Children Research Network.PREDNOS 2 is funded by the National Institute for Health Research Health Technology Assessment Programme (11/129/261). DISCUSSION: We propose that PREDNOS 2 will be a pivotal study that will inform the future standard of care for children with SSNS. If it is possible to reduce the disease relapse rate effectively and safely, this will reduce the morbidity and cost associated with drug treatment, notwithstanding hospital admission and parental absence from employment. TRIAL REGISTRATION: Current Controlled Trials (ISRCTN10900733).

Occurrence of infection among children with nephrotic syndrome during hospitalizations.

AIM: The present study was conducted to investigate the trends of childhood nephrotic syndrome (NS) admissions and factors associated with childhood NS admissions with major infections in Taiwan. METHODS: A retrospective analysis was performed using Taiwan National Health Research Insurance Database (NHIRD) to explore the associated factors and health care burden for childhood NS admissions with major infections in 1997 to 2007. RESULTS: Of 133,927 children, a total of 176 children had NS, which incurred 508 hospital admissions. Nineteen percent of admissions were associated with major infections. Pneumonia was the most common infection (49%), followed by urinary tract infection (UTI), bacteraemia/sepsis, peritonitis and cellulitis. Pneumonia was the most common infection among children age younger than 10 years, whereas UTI was more common among children aged greater than 10 years. NS admission with infections had longer periods of hospital length of stay and higher hospital total costs compared to those without infections. Regression analysis reveals that younger age, regional hospitals, admission hospital located in middle and south areas and admission made in spring were associated with increased risk for developing major infections. CONCLUSIONS: While 19% of childhood NS admissions were associated with major infections, young age, admissions made in spring, located in middle and south Taiwan and in regional hospitals were the major associated factors for infection. Age plays an important role in risk and types of infection.

The impact of pediatric nephrotic syndrome on families.

The objective of our study was to assess the psychologic and economic effects of pediatric nephrotic syndrome (NS) on caregivers. Caregivers of 50 children with NS were compared with a control group of 50 families of children with minor illnesses attending the same outpatient facility. Beck's Depression Inventory (BDI) IA was used to assess the mental status of the primary caregiver. The socioeconomic status of the family was assessed using the modified Kuppuswamy scale. Expenditure for the illness was calculated during parent interviews. The difference between groups was analyzed using analysis of variance (ANOVA) and Duncan's multiple range test. BDI scores signified moderate to severe depression in 48% of NS caregivers compared with 12% controls. The mean BDI score was significantly higher in NS caregivers, correlating positively with disease severity and negatively with socioeconomic status. Expenditure for disease also was significantly higher in families with NS patients, varying between 30% and 60% of monthly income depending on disease severity compared with 6.9% in controls. In 10% of NS families, it was more than total income, forcing families to break into savings or go into debt. Although pediatric NS most commonly has an excellent long-term outcome, it causes significant mental and economic stress on families. Severe forms should be categorized as a chronic illness and be eligible for disability benefits and subsidized travel and medical care. Establishing support groups and supportive care at local levels would help reduce the burden on families of patients wtih NS.

Obstacles to health care: a nurse's experience in Sudan.

Sudan is a country known for its long history of wars, poverty, and disease. These factors combine to cause a high incidence of morbidity and mortality and the inability of the population to seek and receive medical care.

Impact of the cyclosporine-ketoconazole interaction in children with steroid-dependent idiopathic nephrotic syndrome.

BACKGROUND: Children with steroid-dependent nephrotic syndrome experience serious side effects from steroid therapy. Cyclosporine A (CsA), which is an effective agent in the treatment of steroid-dependent nephrotic syndrome, is expensive and, consequently, often unaffordable in developing countries. Many studies have documented the benefit of ketoconazole administration in transplant adults treated with CsA. We have conducted a retrospective study with the objective of addressing cost-savings, safety, and the efficacy of the co-administration of ketoconazole and CsA to children with steroid-dependent nephrotic syndrome. METHODS: This study included 102 nephrotic patients who were steroid-dependent and who received cyclosporine therapy. The commonest pathologic lesions were focal segmental glomerulosclerosis (64 patients) and minimal change disease (36 patients). Among the patients participating in the study, 78 received daily ketoconazole therapy (ketoconazole group) in the form of a 50-mg dose accompanied by an initial one-third decrease in the CsA dose, while 24 received CsA alone (non- ketoconazole group). All of the patients were children (below 18 years), and the male-to-female ratio was 3:1. The mean duration of treatment was 22.9 months. The characteristics of both groups were comparable. RESULTS: Co-administration of ketoconazole significantly reduced mean doses of CsA by 48% with a net cost savings of 38%. It also resulted in a significant improvement in the CsA response and a more successful steroid withdrawal as well as a decrease in the frequency of renal impairment. Liver function tests remained normal in both groups up to and including the final follow-up (mean of 33.6 months). CONCLUSIONS: The co-administration of ketoconazole to CsA in children with idiopathic steroid-dependent nephrotic syndrome safely results in a significant reduction in CsA cost, which causes great concern in developing countries. It may also improve CsA response.

Co-administration of cyclosporine and ketoconazole in idiopathic childhood nephrosis.

The concomitant use of cyclosporine (CsA) and ketoconazole (keto) in children with nephrotic syndrome (NS) has never been reported in the literature. This retrospective cohort study was conducted to investigate cost saving, safety, and efficacy of co-administration of keto and CsA in children with NS. The study included 186 nephrotic children receiving CsA therapy. Most were steroid dependent or resistant, and the most common pathology was focal segmental glomerulosclerosis (62%). Among our patients, 137 received daily keto therapy (keto group) 50 mg/day in addition to CsA, while 49 received CsA alone (non-keto group). The characteristics of both groups were comparable and the mean (+/-SD) duration of treatment was 22.9 +/- 8.1 months. Co-administration of keto significantly reduced the mean dose of CsA with an overall net cost saving of 37%. It also resulted in a significant improvement of CsA response, more successful steroid withdrawal, and decreased the frequency of renal impairment. Keto was generally well tolerated and safe. We conclude that co-administration of low-dose keto with CsA in children with idiopathic NS is safe, significantly reduces the cost of CsA therapy, and may improve the patient outcome.

Levamisole vs. cyclophosphamide for frequently-relapsing steroid-dependent nephrotic syndrome.

A retrospective analysis comparing the first-time use of levamisole (L) or cyclophosphamide (C) as second-line therapy for children with frequently relapsing, steroid-dependent (FR/SD) nephrotic syndrome, was conducted at our center. The relapse rate and the total cumulative dose of prednisone during the year prior to L/C therapy was compared to that during the year following the institution of therapy with L or C in 51 patients, between July 1992 and June 1997. An analysis of covariance was used to adjust the outcome for differences between the 2 groups of treatment in the year prior to second-line drug initiation. In the L group the mean relapse rate was lowered by 0.28 relapses/patient/month and the mean cumulative dose of prednisone was reduced by 336 mg/m2/month versus 0.32 relapses/patient/month and 387 mg/m2/month in the C group (p = 0.395. p = 0.577). No significant difference in the effectiveness of L vs. C for therapy of FR/SD nephrotic syndrome could be identified in our patients. We conclude that L may be considered an alternative for C as a first second-line agent for these patients.