Oral protein energy supplements for children with cystic fibrosis: CALICO multicentre randomised controlled trial. Relationships among nutritional status and skeletal and respiratory muscle function in cystic fibrosis: does early dietary supplementation make a difference? Behavioral intervention to improve calorie intake of children with cystic fibrosis: treatment versus wait list control. Randomised multicentre study of a low-protein diet on the progression of chronic renal failure in children. European Study Group of Nutritional Treatment of Chronic Renal Failure in Childhood. A multicenter, randomized, double-blind, placebo-controlled trial to evaluate the metabolic and respiratory effects of growth hormone in children with cystic fibrosis. Controlled trial of intermittent aerosol therapy with sodium 2-mercaptoethane sulphonate in cystic fibrosis. Effect of double-blind cross-over selenium supplementation on lipid peroxidation markers in cystic fibrosis patients. Treatment and prevention of osteoporosis in juvenile chronic arthritis with disodium clodronate. Effects of a supplemented hypoproteic diet in chronic kidney disease. Effect of a medium dose of ursodeoxycholic acid with or without taurine supplementation on the nutritional status of patients with cystic fibrosis: a randomized, placebo-controlled, crossover trial. Supplement feeds and nitrogen and calorie balance following femoral neck fracture.
To determine whether oral protein energy supplements, used long term in children with cystic fibrosis who are moderately malnourished, improve nutritional and other outcomes.
                Multicentre randomised controlled trial.
                Seven specialist paediatric cystic fibrosis centres and their associated shared care clinics and seven smaller paediatric cystic fibrosis clinics.
                102 children with cystic fibrosis, aged between 2 and 15 years, who were moderately malnourished.
                Oral protein energy supplements in addition to usual dietary advice compared with dietary advice alone, for 12 months.
                Change in body mass index centile over one year.
                Use of supplements was not associated with a change in body mass index centile (mean difference 2.99 centile points, 95% confidence interval -2.70 to 8.68) or other nutritional and spirometric outcomes in this group of children.
                Long term use of oral protein energy supplements did not result in an improvement in nutritional status or other clinical outcomes in children with cystic fibrosis who were moderately malnourished. Oral protein energy supplements should not be regarded as an essential part of the management of this group of children.
                ISRCTN: 95744468. Relationships among nutritional status and skeletal and respiratory muscle function were examined in 16 children with cystic fibrosis (CF) and mild lung disease (FEV1 95 +/- 16% predicted). Subjects were randomly assigned to receive (or not) noninvasive nutritional supplementation at 25% of normal energy recommendations for 6 mo. Skeletal muscle strength and power were similar to those of healthy children as were respiratory muscle strength and endurance. Stepwise-regression analysis indicated that changes in skeletal muscle strength and energy intake correlated significantly with growth [weight (kg) = 1.90 - 0.60 (Tanner Stage) + 0.49 (maximum voluntary strength (Nm) + 0.03 (energy intake, % RNI), r = 0.76, P < 0.05], though body composition, protein biochemistry, muscle power, respiratory muscle strength, and use of dietary supplements did not. Thus, changes in skeletal muscle strength may be a functional index of changes in nutritional status in CF. Dietary supplementation per se was not associated with functional improvement. Changes in calorie intake and weight gain were evaluated in five children with cystic fibrosis (CF) who received behavioral intervention and four children with CF who served as wait list controls. The behavioral intervention was a 6-week group treatment that provided nutritional education plus management strategies aimed at mealtime behaviors that parents find most problematic. The control group was identified prospectively and was evaluated on all dependent measures at the same points in time pre- and posttreatment as the intervention group. Difference scores on calorie intake and weight gain from pre- to posttreatment were compared between groups using t tests for independent samples. The behavioral intervention group increased their calorie intake by 1,032 calories per day, while the control group's intake increased only 244 calories per day from pre- to posttreatment [t(6) = 2.826, p = 0.03]. The intervention group also gained significantly more weight (1.7 kg) than the control group (0 kg) over the 6 weeks of treatment [t(7) = 2.588, p = 0.03] and demonstrated catchup growth for weight, as indicated by improved weight Z scores (-1.18 to -0.738). The control group showed a decline in weight Z scores over this same time period (-1.715 to -1.76). One month posttreatment, the intervention was replicated with two of the four children from the control group. Improved calorie intake and weight gain pre- to posttreatment were again found in these children. At 3- and 6-month follow-up study of children receiving intervention, maintenance of calorie intake and weight gain was confirmed. No changes were found on pulmonary functioning, resting energy expenditure, or activity level pre- to posttreatment. This form of early intervention appears to be promising in improving nutritional status and needs to be investigated over a longer period of time to evaluate the effects of treatment gains on the disease process. Some studies have suggested that a low-protein diet slows the deterioration of renal function in patients with chronic renal failure (CRF). The effects of a low-protein diet on renal function and growth, have not been assessed in a large, prospective randomised trial in children with CRF.
                A 2-year prospective, stratified, and randomised multicentre study recruited 191 patients aged 2-18 years. After a run-in period of at least 6 months, patients were stratified into either a progressive or non-progressive category based on the change in creatinine clearance in this period. The patients were also stratified into three renal-disease categories and then randomly assigned to a control or diet group. In the diet group, the protein intake was the lowest, safe WHO recommendation--i.e., 0.8-1.1 g/kg daily adjusted for age. All patients were advised to have a calorie intake of at least 70% of the WHO recommendations. Glomerular filtration rate (GFR) was measured every 2 months by creatinine clearance; dietary compliance was checked by urinary urea-nitrogen excretion and dietary diaries (weighing method). 112 patients completed an optional third year of the study.
                The low-protein diet did not affect growth. However, there was no effect of diet on the mean decline in creatinine clearance over 2 years (diet vs control: progressive group -9.7 [SD 8.0] vs -10.7 [11.8] mL/min per 1.73 m2; non-progressive group -2.5 [7.5] vs -4.3 [10.0] mL/min per 1.73 m2). Patients classified as having progressive disease were older and had a lower creatinine clearance and a higher blood pressure at randomisation, and had a greater decrease in creatinine clearance than non-progressive patients. On multivariate regression analysis proteinuria (partial R2 = 0.259) and systolic blood pressure (partial R2 = 0.087) were independent predictors of the change in GFR. Similar results were found after the study was extended for a third year.
                A low-protein diet for 3 years did not affect the decrease in renal function in children with CRF. Proteinuria and blood pressure explain a large part of the variability of, and may be causally related to the decline in the GFR. Positive effects of growth hormone therapy on growth, nutritional status, and lung function have been observed in patients with cystic fibrosis, but the current evidence is based on unblinded studies that involved a small number of patients. This trial was designed as a multicenter, randomized, placebo-controlled, double-blind study to assess the efficacy and safety of 2 dosages of growth hormone in cystic fibrosis.
                Sixty-three dystrophic patients with cystic fibrosis were randomly assigned for 24 weeks to 1 of 3 treatment arms: growth hormone dosage of 0.11 IU/kg body weight per day, growth hormone dosage of 0.21 IU/kg body weight per day, or placebo. The 24-week double-blind period was followed by an open treatment period of 24 weeks. The primary outcome measure was the change in forced expiratory volume in 1 second in percentage predicted from baseline. Secondary outcome measures were changes in height, weight, and exercise tolerance.
                Height, growth velocity, and growth factors (insulin-like growth factor 1 and insulin-like growth factor-binding protein 3) increased significantly in both treatment groups, whereas weight gain did not differ between the growth hormone groups and placebo. A trend toward improvement in absolute forced vital capacity was observed in patients who received the higher growth hormone dosage, whereas forced expiratory volume in 1 second did not change significantly with growth hormone treatment. Maximal oxygen uptake during peak exercise increased significantly in treated patients. There were no significant differences in the frequency or severity of adverse effects or in the incidence of abnormalities in glucose metabolism.
                These data suggest that in the group investigated, growth hormone therapy was well tolerated and had positive metabolic effects but did not result in short-term improvement of lung function in patients with cystic fibrosis. Twenty-seven patients with cystic fibrosis completed a controlled trial comparing the effects of an inhaled mucolytic drug, sodium-2-mercaptoethane sulphonate (Mistabron, UCB Pharmaceutical Division, Brussels, Belgium), with inhaled iso-osmolar hypertonic saline. As a group the 22 patients with chronic sputum production showed small but statistically significant improvement in pulmonary function tests after Mistabron therapy, both when compared with a control period, and with iso-osmolar saline results. Subjective measurements by diary card failed to show any changes. No significant changes were found in five patients with no measurable sputum production. The inhalations were given after physiotherapy and were well tolerated. There were no significant side effects. The results suggest that Mistabron has a beneficial therapeutic effect unrelated to its high osmolality, and the intermittent inhalation of Mistabron may have a role in the treatment of selected patients with cystic fibrosis. Lipid peroxidation was assessed in 27 cystic fibrosis children during a double-blind selenium supplementation study (2.8 micrograms of sodium selenite per kg per day) with a placebo control and inversion of treatment periods. Simultaneously, 17 healthy children living in the same area were also investigated as control subjects. Before any treatment whatsoever and despite a selenium status close to those of control subjects, cystic fibrosis patients showed significant increase in plasma lipid peroxidation markers. Thiobarbituric acid reactants (TBARs) were normalized after the first treatment period of 5 months in both cystic fibrosis groups receiving either selenium supplementation or placebo. In this latter group, TBARs were reduced despite a significant decrease in plasma selenium concentrations as compared with the control group. Organic hydroperoxide concentrations were also simultaneously normalized in both cystic fibrosis groups at the end of the second treatment period. These results showed that improvement of lipid peroxidation markers was not related to the selenium supplementation. Nevertheless, oxidative stress sustained by cystic fibrosis children must be taken into account so that it does not aggravate the prognosis of the disease. Osteoporosis is one of the most difficult problems in the management of Chronic Juvenile Arthritis (JCA). The available data suggest that bone loss results from multifactorial processes which lead to bone degradation through the activation of osteoclasts. Biphosphonates are synthetic factors that, once localized on the surface of hydroxyapatite crystals, do not allow either the production or destruction of the crystals. This activity seems to be due to cytotoxicity against osteoclasts and to inhibition of prostaglandin E2 synthesis. There is some evidence that these drugs are effective in the treatment of osteoporosis in several diseases. In an attempt to reduce or prevent osteoporosis in children affected by JCA we started a trial with disodium clodronate, a type of biphosphonate. Thirteen patients were enrolled in the study: 7 received disodium clodronate and 6 acted as control subjects. Before starting the therapy and after one year we performed a CT scan to evaluate the mineral bone density in all patients. The mean bone density increased from a bone mineral content of 129 mg/cc before treatment to 134 mg/cc after treatment (8% increase); control patients passed from 123 mg/cc to 115 mg/cc (7% decrease) in the same period. Only one child stopped treatment because of gastrointestinal side effects. The small number of patients enrolled in the trial does not allow any definite conclusions to be drawn, but the data are interesting and worthy of further study. We assessed the effect of a severe hypoproteic diet supplemented with ketoanalogues (SVLPD) for 48 weeks on certain metabolic disorders of chronic kidney disease (CKD).
                We performed a prospective, open-label, parallel, randomized, controlled trial.
                The study took place in the Nephrology Department at the Dr Carol Davila Teaching Hospital of Nephrology, Bucharest, Romania.
                A total of 53 nondiabetic patients with CKD with an estimated glomerular filtration rate less than 30 mL/min/1.73 m(2) (Modification of Diet in Renal Disease formula), proteinuria less than 1 g/g urinary creatinine, good nutritional status, and anticipated good compliance with the diet were randomly assigned to two groups.
                Group I (n = 27) received the SVLPD (0.3 g/kg/d of vegetable proteins and ketoanalogues, 1 capsule for every 5 kg of ideal body weight per day). Group II (n = 26) continued a conventional low mixed protein diet (0.6 g/kg/d).
                Nitrogen waste products retention and calcium-phosphorus and acid-base disturbances were primary efficacy parameters, and "death" of the kidney or the patient and the estimated glomerular filtration rate were secondary efficacy parameters. The nutritional status and compliance with the diet were predefined as safety variables. There were no differences between groups in any parameter at baseline.
                In the SVLPD group, serum urea significantly decreased (56 +/- 7.9 mmol/L vs. 43.2 +/- 10 mmol/L), and significant improvements in serum bicarbonate (23.4 +/- 2.1 mmol/L vs. 18.1 +/- 1.5 mmol/L), serum calcium (1.10 +/- 0.17 mmol/L vs. 1.00 +/- 0.15 mmol/L at baseline), serum phosphates (1.45 +/- 0.66 mmol/L vs. 1.91 +/- 0.68 mmol/L), and calcium-phosphorus product (1.59 +/- 0.11 mmol(2)/L(2) vs. 1.91 +/- 0.10 mmol(2)/L(2)) were noted after 48 weeks. No death was registered in any group. Significantly lower percentages of patients in group I required renal replacement therapy initiation (4% vs. 27%). After 48 weeks, estimated glomerular filtration rate did not significantly change in patients receiving SVLPD (0.26 +/- 0.08 mL/s vs. 0.31 +/- 0.08 mL/s at baseline), but significantly decreased in controls (0.22 +/- 0.09 mL/s vs. 0.30 +/- 0.07 mL/s). The compliance with the keto-diet was good in enrolled patients. No significant changes in any of the parameters of the nutritional status and no adverse reactions were noted.
                SVLPD seems to ameliorate the nitrogen waste products retention and acid-base and calcium-phosphorus metabolism disturbances and to postpone the renal replacement therapy initiation, preserving the nutritional status in patients with CKD. Ursodeoxycholic acid administration has been reported to improve cholestasis and inflammatory activity in primary biliary cirrhosis and, in an uncontrolled study, also in young adults with cystic fibrosis (CF) and chronic cholestasis. As an improvement in nutritional status was also observed in these young adult patients, we investigated whether the administration of a medium dose of ursodeoxycholic acid ameliorates the nutritional status of malnourished young adult CF patients with chronic liver disease. The study included 51 patients (27 male patients and 24 female patients; age range, 8-32 years; median, 14) with body mass percentiles < 90%. Patients were randomly assigned to receive either ursodeoxycholic acid (10-12 mg/kg/day) alone or with taurine (18-22 mg/kg/day). Patients were followed in a crossover fashion within each group; 6 months of treatment was randomly alternated with 6 months of placebo. Nine patients dropped out before concluding the study. Liver function tests, nutritional status, and coefficients of fat absorption were determined at entry and after each 6 months of placebo or treatment. Nutritional status and fat absorption were not significantly modified by either treatment. Liver function tests improved after ursodeoxycholic acid administration only in patients with concomitant chronic liver disease. Our findings indicate that 6 months of therapy with a medium dose of ursodeoxycholic acid, either alone or with taurine, does not improve the nutritional status of young malnourished CF patients. Higher doses given for longer periods might be worth investigating. A 10 day study of nitrogen and calorie balance has been undertaken in 61 women patients aged 65-96 years (mean age 81 years) with femoral neck fractures. All underwent fracture surgery with an inhalation anaesthetic lasting from 45 min to 2 h. Intake of ward food varied widely but was always low with a mean of 127 mg N kg-1 and 17 kcal kg-1 daily. Daily nitrogen production was 85-250 mg N kg-1 (mean 158 mg N kg-1) and calorie expenditure was 17-48 kcal kg-1 (mean 32 kcal kg-1). These were greatest in trochanteric fracture patients. Of the 61 patients, 90 per cent were in negative nitrogen balance with a mean 8 day deficit of 411 mg N kg-1 and all in negative calorie balance, mean 141 kcal kg-1. The deficits were greatest in trochanteric fracture patients. Sip feeding with supplementary enriched drinks raised protein and calorie intake substantially. Both nitrogen and calorie balance were significantly improved, but large calorie deficits remained; intolerance of the supplements proved to be a handicap in correcting the deficits in many patients.
Oral protein calorie supplements are widely used to improve the nutritional status of children with a number of chronic diseases. We identified a small number of studies assessing these products in children with cystic fibrosis, but were unable to draw any conclusions based on the limited data extracted. We recommend a series of large, randomised controlled trials be undertaken investigating the use of these products in children with different chronic diseases. Until further data are available, we suggest these products are used with caution.