Human health risk assessment of heavy metal concentration in surface water of Sosian river, Eldoret town, Uasin-Gishu County Kenya.

Heavy metal pollution in surface waters has become a major worldwide issue as people tend to settle where there is readily available source of water like a river. This research evaluates the causes, concentration and associated health risks of heavy metals in River Sosiani as it passes through the town of Eldoret. Seven water samples were collected and analysed for zinc (Zn), copper (Cu) and lead (Pb. The results disclosed that Pb concentrations were estimated to be in the range of 0.06 mg/l to 0.23 mg/l, higher than the permitted limit by WHO of 0.01 mg/l. Cu and Zn concentration levels were below the permissible limits. The chronic daily intake (CDI) indicated that total hazard quotient of non-cancer risk of Pb was above one and the total HI values for children were greatly elevated compared to those of adults in the studied area. This showed a high risk in exposure to Pb. Health human risk was assessed and the incremental life cancer risk (ILCR) values of Pb for children and adults in all sites were found to be negligible with values below 10-6. However, there is higher cancer and non-cancer risk for children than adults as far as lead metal is concerned. Therefore, measures should be taken in accordance with the standards to prevent potential risk of the river pollution.•Human activities make a significant contribution to heavy metal pollution to surface waters which is a threat to humans.•Water from Sosiani River is not safe for use domestically as far as lead metal levels are concerned.•The results of this study can be used by decision makers to develop measures which can improve the quality of water in the river catchment.

Extra-mandibular Osteoradionecrosis after the Treatment of Head and Neck Cancer.

AIMS: Osteoradionecrosis (ORN) is a serious toxicity of head and neck radiotherapy. It predominantly affects the mandible. Extra-mandibular ORN is rare. The aim of this study was to report the incidence and outcomes of extra-mandibular ORNs from a large institutional database. MATERIALS AND METHODS: In total, 2303 head and neck cancer patients were treated with radical or adjuvant radiotherapy. Of these, extra-mandibular ORN developed in 13 patients (0.5%). RESULTS: Maxillary ORNs (n = 8) were a consequence of the treatment of various primaries (oropharynx = 3, sinonasal = 2, maxilla = 2, parotid = 1). The median interval from the end of radiotherapy to the development of ORN was 7.5 months (range 3-42 months). The median radiotherapy dose in the centre of the ORN was 48.5 Gy (range 22-66.5 Gy). Four patients (50%) healed in 7, 14, 20 and 41 months. All temporal bone ORNs (n = 5) developed after treatment to the parotid gland (of a total of 115 patients who received radiotherapy for parotid gland malignancy). The median interval from the end of radiotherapy to the development of ORN was 41 months (range 20-68 months). The median total dose in the centre of the ORN was 63.5 Gy (range 60.2-65.3 Gy). ORN healed in only one patient after 32 months of treatment with repeated debridement and topical betamethasone cream. CONCLUSION: Extra-mandibular ORN is a rare late toxicity and this current study provides useful information on its incidence and outcome. The risk of temporal bone ORN should be considered in the treatment of parotid malignancies and patients should be counselled. More research is required to determine the optimal management of extra-mandibular ORN, particularly on the role of the PENTOCLO regimen.

Osteoradionecrosis after treatment of head and neck cancer: a comprehensive analysis of risk factors with a particular focus on role of dental extractions.

In head and neck cancer (HNC), osteoradionecrosis (ORN) is one of the most significant complications of radiotherapy (RT). With an absence of effective non-surgical treatment, prevention of the development of ORN is the best approach. The purpose of this study was to identify the risk factors for the development of ORN in HNC. Records of 1,118 patients with HNC treated with radical RT (≥55Gy) from January 2010 to December 2019 were reviewed. After applying the exclusion criteria, 935 patients were included in the final analysis. In patients with confirmed ORN, exact RT doses were mapped. In total, 91 patients were found (9.7%) with a median (range) time of eight (3-89) months to the development of ORN. Smoking, having a primary site in the oropharynx, bone surgery before adjuvant RT, the addition of concurrent chemotherapy, the presence of xerostomia, dental extraction pre-RT, the time ≤20 days between dental extraction and start of RT, and receiving >55Gy RT dose were significant factors for its development. This comprehensive analysis including the precise RT dose mapping has shown the risk factors for the development of ORN. In practice, every effort should be made to avoid these risk factors without compromising the oncology treatment. The findings of this analysis may provide a basis for future prospective research on this topic.

Addressing the pitfalls when designing intervention studies to discover and validate biomarkers of habitual dietary intake.

INTRODUCTION: Dietary exposure monitoring within populations is reliant on self-reported measures such as Food Frequency Questionnaires and diet diaries. These methods often contain inaccurate information due to participant misreporting, non-compliance and bias. Urinary metabolites derived from individual foods could provide additional objective indicators of dietary exposure. For biomarker approaches to have utility it is essential that they cover a wide-range of commonly consumed foods and the methodology works in a real-world environment. OBJECTIVES: To test that the methodology works in a real-world environment and to consider the impact of the major sources of likely variance; particularly complex meals, different food formulations, processing and cooking methods, as well as the dynamics of biomarker duration in the body. METHODS: We designed and tested a dietary exposure biomarker discovery and validation strategy based on a food intervention study involving free-living individuals preparing meals and collecting urine samples at home. Two experimental periods were built around three consecutive day menu plans where all foods and drinks were provided (n = 15 and n = 36). RESULTS: The experimental design was validated by confirming known consumption biomarkers in urinary samples after the first menu plan. We tested biomarker performance with different food formulations and processing methods involving meat, wholegrain, fruits and vegetables. CONCLUSION: It was demonstrated that spot urine samples, together with robust dietary biomarkers, despite major sources of variance, could be used successfully for dietary exposure monitoring in large epidemiological studies.

Effects of vitamin C supplementation on glycaemic control: a systematic review and meta-analysis of randomised controlled trials.

Randomised controlled trials (RCTs) have observed contrasting results on the effects of vitamin C on circulating biomarkers of glycaemic and insulin regulation. We conducted a systematic review and meta-analysis of RCTs testing the effect of vitamin C administration on glucose, HbA1c and insulin concentrations. Four databases (PubMed, Embase, Scopus and Cochrane Library) were used to retrieve RCTs published from inception until April 2016 and testing the effects of vitamin C in adult participants. The screening of 2008 articles yielded 22 eligible studies (937 participants). Overall, vitamin C did not modify glucose, HbA1c and insulin concentrations. However, subgroup analyses showed that vitamin C significantly reduced glucose concentrations (-0.44 mmol/l, 95% CI: -0.81, -0.07, P=0.01) in patients with type 2 diabetes and in interventions with a duration greater than 30 days (-0.53%, 95% CI: -0.79, -0.10, P=0.02). Vitamin C administration had greater effects on fasting (-13.63 pmol/l, 95% CI: -22.73, -4.54, P<0.01) compared to postprandial insulin concentration. Meta-regression analyses showed that age was a modifier of the effect of vitamin C on insulin concentration. Furthermore, the effect size was associated with baseline BMI and plasma glucose levels, and with the duration of the intervention. In conclusion, greater reduction in glucose concentrations observed in patients with diabetes, older individuals and with more prolonged supplementation. Personalised interventions with vitamin C may represent a feasible future strategy to enhance benefits and efficacy of interventions. Nevertheless, results need to be interpreted cautiously due to limitations in the primary studies analysed.

Dosimetric and radiobiological comparison of helical tomotherapy, forward-planned intensity-modulated radiotherapy and two-phase conformal plans for radical radiotherapy treatment of head and neck squamous cell carcinomas.

OBJECTIVES: The usual radical radiotherapy treatment prescribed for head and neck squamous cell carcinoma (HNSCC) is 70 Gy (in 2 Gy per fraction equivalent) administered to the high-risk target volume (TV). This can be planned using either a forward-planned photon-electron junction technique (2P) or a single-phase (1P) forward-planned technique developed in-house. Alternatively, intensity-modulated radiotherapy (IMRT) techniques, including helical tomotherapy (HT), allow image-guided inversely planned treatments. This study was designed to compare these three planning techniques with regards to TV coverage and the dose received by organs at risk. METHODS: We compared the dose-volume histograms and conformity indices (CI) of the three planning processes in five patients with HNSCC. The tumour control probability (TCP), normal tissue complication probability (NTCP) and uncomplicated tumour control probability (UCP) were calculated for each of the 15 plans. In addition, we explored the radiobiological rationality of a dose-escalation strategy. RESULTS: The CI for the high-risk clinical TV (CTV1) in the 5 patients were 0.78, 0.76, 0.82, 0.72 and 0.81 when HT was used; 0.58, 0.56, 0.47, 0.35 and 0.60 for the single-phase forward-planned technique and 0.46, 0.36, 0.29, 0.22 and 0.49 for the two-phase technique. The TCP for CTV1 with HT were 79.2%, 85.2%, 81.1%, 83.0% and 53.0%; for single-phase forward-planned technique, 76.5%, 86.9%, 73.4%, 81.8% and 31.8% and for the two-phase technique, 38.2%, 86.2%, 42.7%, 0.0% and 3.4%. Dose escalation using HT confirmed the radiobiological advantage in terms of TCP. CONCLUSION: TCP for the single-phase plans was comparable to that of HT plans, whereas that for the two-phase technique was lower. Centres that cannot provide IMRT for the radical treatment of all patients could implement the single-phase technique as standard to attain comparable TCP. However, IMRT produced better UCP, thereby enabling the exploration of dose escalation.

Prevention and treatment of renal disease in Henoch-Schönlein purpura: a systematic review.

OBJECTIVE: To determine the benefits and harms of therapies used to prevent or treat renal involvement in Henoch-Schönlein purpura. DESIGN: Systematic review of randomised controlled trials. SETTING: Secondary and tertiary paediatric and paediatric nephrology services. SUBJECTS: Ten trials involving 1230 children aged less than 18 years. MAIN OUTCOME MEASURES: Persistent proteinuria and/or haematuria. RESULTS: Meta-analyses of four trials showed no significant difference in the risk of persistent kidney disease at 6 months (379 children; relative risk (RR) 0.51, 95% CI 0.24 to 1.11) and 12 months (498 children; RR 1.02, 95% CI 0.40 to 2.62) in children given prednisone for 14-28 days at presentation of Henoch-Schönlein purpura compared with placebo or supportive treatment. In children with severe renal disease, there was no significant difference in the risk of persistent renal disease with cyclophosphamide compared with supportive treatment (one trial; 56 children; RR 1.07, 95% CI 0.65 to 1.78) and with cyclosporin compared with methylprednisolone (one trial; 19 children; RR 0.39; 95% CI 0.14 to 1.06). CONCLUSIONS: Data from randomised trials for any intervention used to improve renal outcomes in children with Henoch-Schönlein purpura are very sparse except for short-term prednisone, which has not been shown to be effective.

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.

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.

Correction of chronic metabolic acidosis for chronic kidney disease patients.

BACKGROUND: Metabolic acidosis is a feature of chronic kidney disease (CKD) due to the reduced capacity of the kidney to synthesise ammonia and excrete hydrogen ions. It has adverse consequences on protein and muscle metabolism, bone turnover and the development of renal osteodystrophy. Metabolic acidosis may be corrected by oral bicarbonate supplementation or in dialysis patients by increasing the bicarbonate concentration in dialysate fluid. OBJECTIVES: To examine the benefits and harms of treating metabolic acidosis in patients with CKD, both prior to reaching end-stage renal disease (ESRD) or whilst on renal replacement therapy (RRT), with sodium bicarbonate or increasing the bicarbonate concentration of dialysate. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library, issue 4 2005), Cochrane Renal Group's specialised register (October 2005), MEDLINE (1966 - October 2005) and EMBASE (1980 - October 2005). SELECTION CRITERIA: Randomised controlled trials (RCTs), crossover RCTs and quasi-RCTs investigating the correction of chronic metabolic acidosis in adults or children with CKD. DATA COLLECTION AND ANALYSIS: Outcomes were analysed using relative risk (RR) and weighted mean difference (MD) for continuous measures. MAIN RESULTS: We identified three trials in adult dialysis patients (n = 117). There were insufficient data for most outcomes for meta-analysis. In all three trials acidosis improved in the intervention group though there was variation in achieved bicarbonate level. There was no evidence of effect on blood pressure or sodium levels. Some measures of nutritional status/protein metabolism (e.g. SGA, NP NA) were significantly improved by correction in the one trial that looked in these in detail. There was heterogeneity of the effect on serum albumin in two trials. Serum PTH fell significantly in the two trials that estimated this, there was no significant effect on calcium or phosphate though both fell after correction. Complex bone markers were assessed in one study, with some evidence for a reduction in bone turnover in those with initial high bone turnover and an increase in low turnover patients. The studies were underpowered to assess clinical outcomes, in the one study that did there was some evidence for a reduction in hospitalisation after correction. AUTHORS' CONCLUSIONS: The evidence for the benefits and risks of correcting metabolic acidosis is very limited with no RCTs in pre-ESRD patients, none in children, and only three small trials in dialysis patients. These trials suggest there may be some beneficial effects on both protein and bone metabolism but the trials were underpowered to provide robust evidence.

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.

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.

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. Children with untreated nephrotic syndrome frequently die from infections. The majority of children with nephrotic syndrome respond to corticosteroids. However about 70% of children experience a relapsing course with recurrent episodes of oedema and proteinuria. Corticosteroid usage has reduced the mortality rate in childhood nephrotic syndrome to around 3%, with infection remaining the most important cause of death. However corticosteroids have known adverse effects such as obesity, poor growth, hypertension, diabetes mellitus, osteoporosis and adrenal suppression. The original treatment schedules for childhood nephrotic syndrome were developed in an ad hoc manner. The optimal doses and durations of corticosteroid therapy that are most beneficial and least harmful have not been clarified. OBJECTIVES: The aim of this review was to determine the benefits and harms of different corticosteroid regimens in preventing relapse in children with steroid sensitive nephrotic syndrome (SSNS). SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), Cochrane Renal Group Specialised Register (July 2002), MEDLINE (1966 - July 2002) and EMBASE (1980 - July 2002) without language restriction, reference lists of articles, abstracts from conference proceedings and contact with known investigators in the area. SELECTION CRITERIA: Randomised controlled trials were included if they were carried out in children (aged three months to 18 years) in their initial or subsequent episode of SSNS, if they compared different durations, total doses or other dose strategies using prednisone or other corticosteroid agent and if they had outcome data at six months or more. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed all eligible studies for inclusion, assessed study quality and extracted data. The principle outcome measure was the number of children with and without relapse after six and 12-24 months. Secondary outcomes sought included the number of children who developed frequently relapsing nephrotic syndrome and adverse events. A random effects model was used to estimate summary effect measures (relative risk (RR), risk difference (RD)) after testing for heterogeneity. Meta-regression was used to explore potential between-study differences due to the baseline risk of relapse, study quality and types of interventions used. MAIN RESULTS: Nineteen trials have been included in this review. A meta-analysis of six trials, which compared two months of prednisone with three months or more in the first episode, showed that the longer duration significantly reduced the risk of relapse at 12 - 24 months (RR 0.70; 95% CI 0.58 to 0.84) without an increase in adverse events. There was an inverse linear relationship between the duration of treatment and risk of relapse (RR = 1.26 - 0.112 duration; r(2) = 0.56; p = 0.03). The number of children who became frequent relapsers and the mean relapse rate/patient/year were also significantly reduced without increase in serious adverse events. In children with frequently relapsing nephrotic syndrome, deflazacort was significantly more effective in maintaining remission than prednisone (RR 0.44; 95% CI 0.25 to 0.78). REVIEWERS' 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. In a population with 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 be expected to reduce the number of children experiencing a relapse by about 33%. In children who relapse frequently, deflazacort deserves further study.

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. Children with untreated nephrotic syndrome frequently die from infections. The majority of children with nephrotic syndrome respond to corticosteroids. However about 70% of children experience a relapsing course with recurrent episodes of oedema and proteinuria. Corticosteroid usage has reduced the mortality rate in childhood nephrotic syndrome to around 3%, with infection remaining the most important cause of death. However corticosteroids have known adverse effects such as obesity, poor growth, hypertension, diabetes mellitus, osteoporosis and adrenal suppression. The original treatment schedules for childhood nephrotic syndrome were developed in an ad hoc manner. The optimal doses and durations of corticosteroid therapy that are most beneficial and least harmful have not been clarified. OBJECTIVES: The aim of this review was to determine the benefits and harms of different corticosteroid regimens in preventing relapse in children with steroid sensitive nephrotic syndrome (SSNS). SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), Cochrane Renal Group Specialised Register (July 2002), MEDLINE (1966 - July 2002) and EMBASE (1980 - July 2002) without language restriction, reference lists of articles, abstracts from proceedings and contact with known investigators in the area. SELECTION CRITERIA: Randomised controlled trials were included if they were carried out in children (aged three months to 18 years) in their initial or subsequent episode of SSNS, if they compared different durations, total doses or other dose strategies using prednisone or other corticosteroid agent and if they had outcome data at six months or more. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed all eligible studies for inclusion, assessed study quality and extracted data. The principle outcome measure was the number of children with and without relapse after six and 12-24 months. Secondary outcomes sought included the number of children who developed frequently relapsing nephrotic syndrome and adverse events. A random effects model was used to estimate summary effect measures (relative risk (RR), risk difference (RD)) after testing for heterogeneity. Meta-regression was used to explore potential between-study differences due to the baseline risk of relapse, study quality and types of interventions used. MAIN RESULTS: Five additional trials were included in the review for a total of 17 trials. A meta-analysis of six trials, which compared two months of prednisone with three months or more in the first episode, showed that the longer duration significantly reduced the risk of relapse at 12 - 24 months (RR 0.70; 95% CI 0.58 to 0.84) without an increase in adverse events. There was an inverse linear relationship between the duration of treatment and risk of relapse (RR = 1.26 - 0.112 duration; r(2) = 0.56; p = 0.03). The number of children who became frequent relapsers and the mean relapse rate/patient/year were also significantly reduced without increase in serious adverse events. In children with frequently relapsing nephrotic syndrome, deflazacort was significantly more effective in maintaining remission than prednisone (RR 0.44; 95% CI 0.25 to 0.78). REVIEWER'S 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. In a population with 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 be expected to reduce the number of children experiencing a relapse by about 33%. In children who relapse frequently, deflazacort deserves further study.

Transforming growth factor-beta 1 does not relate to hypertension in pre-eclampsia.

1. Pre-eclampsia is a human disease of pregnancy characterized by high blood pressure, proteinuria and end-organ damage, if severe. Pre-eclampsia is thought to be related to changes in early placental development, with the formation of a shallower than normal placental bed. 2. Transforming growth factor (TGF)-beta1 is a multifunctional fibrogenic growth factor involved in immune regulation that is elevated in some populations with a high risk of hypertensive end-organ disease related to increases in endothelin release. Transforming growth factor-beta1 is also an important factor in placental implantation. Alterations in TGF-beta1 may be related to abnormal placental development in early pregnancy and, thus, are a candidate for the development of hypertension in pre-eclampsia. 3. The aim of the present study was to examine the placental distribution and serum concentration of TGF-beta1 in patients with pre-eclampsia compared with normal pregnancy. 4. Patients with pre-eclampsia (n = 12) were compared with patients with normal pregnancy (n = 14). Transforming growth factor-beta1 was determined by TGF-beta1 Max ELISA (Promega, Madsion, WI, USA) after serum dilution (1/150) and acid activation. Placental distribution was determined by immunostaining with TGF-beta1 (Santa Cruz, Santa Cruz, CA, USA; 20 ng/mL) and the villi and decidual trophoblast were scored for intensity and extent of staining. 5. Patients with pre-eclampsia had a mean gestational age of 36 weeks, whereas those with a normal pregnancy had a mean gestational age of 39.0 +/- 0.4 weeks. There was no difference in TGF-beta1 concentration between the two groups (mean (+/-SEM) 27.1 +/- 1.0 vs 26.4 +/- 0.7 pg/mL for normal pregnancy and pre-eclampsia, respectively; P = 0.73, Mann-Whitney U-test). There was no correlation between systolic or diastolic blood pressure and TGF-beta1 concentration (regression analysis P = 0.4 and 0.2). Immunostaining was absent in the villous trophoblast cells and endovascular and extravillous trophoblast of term placentas. 6. Although TGF-beta1 is present in trophoblast cells in early pregnancy during placental development, TGF-beta1 concentrations were not increased in the placenta at term in pre-eclampsia and there was no correlation between blood pressure and serum TGF-beta1, suggesting that TGF-beta1 does not play a role in the development of late gestation pre-eclampsia and hypertension.