Randomised controlled trial of three day versus 10 day intravenous antibiotics in acute pyelonephritis: effect on renal scarring.

BACKGROUND: Acute pyelonephritis often leaves children with permanent renal scarring. AIMS: To compare the prevalence of scarring following initial treatment with antibiotics administered intravenously for 10 or three days. METHODS: In a prospective two centre trial, 220 patients aged 3 months to 16 years with positive urine culture and acute renal lesions on initial DMSA scintigraphy, were randomly assigned to receive intravenous ceftriaxone (50 mg/kg once daily) for 10 or three days, followed by oral cefixime (4 mg/kg twice daily) to complete a 15 day course. After three months, scintigraphy was repeated in order to diagnose renal scars. RESULTS: Renal scarring developed in 33% of the 110 children in the 10 day intravenous group and 36% of the 110 children in the three day group. Children older than 1 year had more renal scarring than infants (42% (54/129) and 24% (22/91), respectively). After adjustment for age, sex, duration of fever before treatment, degree of inflammation, presence of vesicoureteric reflux, and the patients' recruitment centres, there was no significant difference between the two treatments on renal scarring. During follow up, 15 children had recurrence of urinary infection with no significant difference between the two treatment groups. CONCLUSION: In children with acute pyelonephritis, initial intravenous treatment for 10 days, compared with three days, does not significantly reduce the development of renal scarring.     

Randomised trial of oral versus sequential intravenous/oral cephalosporins in children with pyelonephritis

The hypothesis was tested that oral antibiotic treatment in children with acute pyelonephritis and scintigraphy-documented lesions is equally as efficacious as sequential intravenous/oral therapy with respect to the incidence of renal scarring. A randomised multi-centre trial was conducted in 365 children aged 6 months to 16 years with bacterial growth in cultures from urine collected by catheter. The children were assigned to receive either oral ceftibuten (9 mg/kg once daily) for 14 days or intravenous ceftriaxone (50 mg/kg once daily) for 3 days followed by oral ceftibuten for 11 days. Only patients with lesions detected on acute-phase dimercaptosuccinic acid (DMSA) scintigraphy underwent follow-up scintigraphy. Efficacy was evaluated by the rate of renal scarring after 6 months on follow-up scintigraphy. Of 219 children with lesions on acute-phase scintigraphy, 152 completed the study; 80 (72 females, median age 2.2 years) were given ceftibuten and 72 (62 females, median age 1.6 years) were given ceftriaxone/ceftibuten. Patients in the intravenous/oral group had significantly higher C-reactive protein (CRP) concentrations at baseline and larger lesion(s) on acute-phase scintigraphy. Follow-up scintigraphy showed renal scarring in 21/80 children treated with ceftibuten and 33/72 with ceftriaxone/ceftibuten (p = 0.01). However, after adjustment for the confounding variables (CRP and size of acute-phase lesion), no significant difference was observed for renal scarring between the two groups (p = 0.2). Renal scarring correlated with the extent of the acute-phase lesion (r = 0.60, p < 0.0001) and the grade of vesico-ureteric reflux (r = 0.31, p = 0.03), and was more frequent in refluxing renal units (p = 0.04). The majority of patients, i.e. 44 in the oral group and 47 in the intravenous/oral group, were managed as out-patients. Side effects were not observed. From this study, we can conclude that once-daily oral ceftibuten for 14 days yielded comparable results to sequential ceftriaxone/ceftibuten treatment in children aged 6 months to 16 years with DMSA-documented acute pyelonephritis and it allowed out-patient management in the majority of these children.     

Randomised controlled trial of intravenous maintenance fluids

Aim:   Traditional paediatric intravenous maintenance fluids are prescribed using hypotonic fluids and the weight-based 4:2:1 formula for administration rate. However, this may cause hyponatraemia in sick and post-operative children. We studied the effect of two types of intravenous maintenance fluid and two administration rates on plasma sodium concentration in intensive care patients.
Methods:   A Factorial-design, double-blind, randomised controlled trial was used. We randomised 50 children with normal electrolytes without hypoglycaemia who needed intravenous maintenance fluids for >12 h to 0.9% saline (normal saline) or 4% dextrose and 0.18% saline (dextrose saline), at either the traditional maintenance fluid rate or 2/3 of that rate. The main outcome measure was change in plasma sodium from admission to 12–24 h later.
Results:   Fifty patients (37 surgical) were enrolled. Plasma sodium fell in all groups: mean fall 2.3 (standard deviation 4.0) mmol/L. Fluid type ( P  = 0.0063) but not rate ( P  = 0.12) was significantly associated with fall in plasma sodium. Dextrose saline produced a greater fall in plasma sodium than normal saline: difference 3.0, 95% confidence interval 0.8–5.1 mmol/L. Full maintenance rate produced a greater fall in plasma sodium than restricted rate, but the difference was small and non-significant: 1.6 (−0.7, 3.9) mmol/L. Fluid type, but not rate, remained significant after adjustment for surgical status. One patient, receiving normal saline at restricted rate, developed asymptomatic hypoglycaemia.
Conclusion:   Sick and post-operative children given dextrose saline at traditional maintenance rates are at risk of hyponatraemia.     

Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea

OBJECTIVE—To evaluate the impact of zinc supplementation on the clinical course, stool weight, duration of diarrhoea, changes in serum zinc, and body weight gain of children with acute diarrhoea.
DESIGN—Randomised double blind controlled trial. Children were assigned to receive zinc (20 mg elemental zinc per day) containing multivitamins or control group (zinc-free multivitamins) daily in three divided doses for two weeks.
SETTING—A diarrhoeal disease hospital in Dhaka, Bangladesh.
PATIENTS—111 children, 3 to 24 months old, below 76% median weight for age of the National Center for Health Statistics standard with acute diarrhoea. Children with severe infection and/or oedema were excluded.
MAIN OUTCOME MEASURES—Total diarrhoeal stool output, duration of diarrhoea, rate of weight gain, and changes in serum zinc levels after supplementation.
RESULTS—Stool output was 28% less and duration 14% shorter in the zinc supplemented group than placebo (p = 0.06). There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter (less than 95% height for age), 239v 326 g/kg (p < 0.04), and who had a lower initial serum zinc (< 14 mmol/l), 279 v 329 g/kg (p < 0.05); a shortening of mean time to recovery occurred (4.7 v 6.2 days, p < 0.04) in those with lower serum zinc. There was an increase in mean serum zinc in the zinc supplemented group (+2.4 v −0.3 µmol/l, p < 0.001) during two weeks of supplementation, and better mean weight gain (120 v 30 g, p < 0.03) at the time of discharge from hospital.
CONCLUSIONS—Zinc supplementation is a simple, acceptable, and affordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished.

     

Home intravenous versus oral antibiotics following appendectomy for perforated appendicitis in children: a randomized controlled trial

Purpose

To compare the effect of home intravenous (IV) versus oral antibiotic therapy on complication rates and resource utilization following appendectomy for perforated appendicitis.

Methods

This was a randomized controlled trial of patients aged 4–17 with surgically treated perforated appendicitis from January 2011 to November 2013. Perforation was defined intraoperatively and divided into three grades: I—contained perforation, II—localized contamination to right gutter/pelvis, and III—diffuse contamination. Patients were randomized to complete a ten-day course of home antibiotic therapy with either IV ertapenem or oral amoxicillin–clavulanate. Thirty-day postoperative complication rates including abscess, readmission, wound infection, and charges were compared.

Results

Eighty-two patients were enrolled. Forty four (54%) were randomized to the IV group and 38 (46%) to the oral group. IV patients were older (12.3?±?3.6 versus 10.1?±?3.6, p?<?0.05) with higher BMI (20.9?±?5.8 versus 17.9?±?3.5, p?<?0.05). There were no differences in gender, comorbidities, or perforation grade (I—20.4% vs. 26.3%, II—36.4% vs. 34.2%, III—43.2% vs. 39.5%, all p?>?0.05). Comparing IV to oral, there was no difference in length of stay (4.4?±?1.5 versus 4.4?±?2.0 days, p?>?0.05), postoperative abscess rate (11.6% vs. 8.1%, p?>?0.05), or readmission rate (14.0% vs. 16.2%, p?>?0.05). Hospital and outpatient charges were higher in the IV group (p?<?0.0001).

Conclusion

Oral antibiotics had equivalent outcomes and incurred fewer charges than IV antibiotics following appendectomy for perforated appendicitis.

     

Randomised controlled trial of aminophylline for severe acute asthma.

OBJECTIVES: To determine whether children with severe acute asthma treated with large doses of inhaled salbutamol, inhaled ipratropium, and intravenous steroids are conferred any further benefits by the addition of aminophylline given intravenously. STUDY DESIGN: Randomised, double blind, placebo controlled trial of 163 children admitted to hospital with asthma who were unresponsive to nebulised salbutamol. RESULTS: The placebo and treatment groups of children were similar at baseline. The 48 children in the aminophylline group had a greater improvement in spirometry at six hours and a higher oxygen saturation in the first 30 hours. Five subjects in the placebo group were intubated and ventilated after enrollment compared with none in the aminophylline group. CONCLUSIONS: Aminophylline continues to have a place in the management of severe acute asthma in children unresponsive to initial treatment.     

Randomised controlled trial of biofeedback training in persistent encopresis with anismus

BACKGROUND—Paradoxical external anal sphincter contraction during attempted defecation (anismus) is thought to be an important contributor to chronic faecal retention and encopresis in children. Biofeedback training can be used to teach children to abolish this abnormal contraction.
METHODS—A randomised controlled trial in medical treatment resistant and/or treatment dependent children with anismus using surface electromyographic (EMG) biofeedback training to determine whether such training produces sustained faecal continence. Up to four sessions of biofeedback training were conducted at weekly intervals for each patient. Anorectal manometry was performed before randomisation and six months later. Parents of patients completed the "child behaviour checklist" (CBCL) before randomisation and at follow up.
RESULTS—Sixty eight children underwent anorectal manometry and EMG. Of these, 29 had anismus (ages 4-14 years) and were randomised to either EMG biofeedback training and conventional medical treatment (BFT) (n = 14) or to conventional medical treatment alone (n = 15). All but one child were able to learn relaxation of the external anal sphincter on attempted defecation. At six months'' follow up, laxative free remission had been sustained in two of 14 patients in the BFT group and in two of 15 controls (95% confidence interval (CI) on difference, −24% to 26%). Remission or improvement occurred in four of 14 patients in the BFT group and six of 15 controls (95% CI on difference, −46% to 23%). Of subjects available for repeat anorectal manometry and EMG at six months, six of 13 in the BFT group still demonstrated anismus v 11 of 13 controls (95% CI on difference, −75% to −1%). Of the four patients in full remission at six months, only one (in the BFT group) did not exhibit anismus. Rectal hyposensitivity was not associated with remission or improvement in either of the groups. Mean CBCL total behaviour problem scores were not significantly different between the BFT and control groups, but there was a significant improvement in CBCL school scale scores in the BFT group, and this improvement was significantly greater than that seen in the control group.
CONCLUSIONS—The result of this study, together with those reported in other controlled trials, argues against using biofeedback training in children with encopresis.

     

Randomised controlled trial of tyrosine supplementation on neuropsychological performance in phenylketonuria

OBJECTIVE—To test the efficacy of tyrosine supplementation, as an adjunct to dietary treatment, on neuropsychological test performance in individuals with phenylketonuria.
DESIGN—A randomised controlled trial of tyrosine supplementation using a double blind crossover procedure with three four week phases.
SETTING—The Hospital for Sick Children, Toronto.
PARTICIPANTS—21 individuals with phenylketonuria (ages 6 to 28 years, mean 11.3).
INTERVENTION—Participants were given 100 mg/kg body weight/d of L-tyrosine or L-alanine (placebo).
RESULTS—At baseline, performance on several of the neuropsychological test measures was correlated with tyrosine levels. Dietary supplements of tyrosine increased plasma tyrosine concentrations; however, no change in test performance was found across the tyrosine and placebo phases of the study.
CONCLUSIONS—Tyrosine supplementation of this type does not appear to alter neuropsychological performance in individuals with phenylketonuria.

     

Randomised controlled trial of cisapride in feed intolerance in preterm infants

AIM—To assess the efficacy of cisapride in reducing the time required to establish enteral feeds in preterm infants.
METHODS—A randomised, double blind, placebo controlled trial was conducted of 34 infants of ⩽ 32 weeks of gestation, assigned to receive either cisapride 0.2 mg/kg/dose four times daily (n=18) or placebo (n=16).
RESULTS—The time taken by the babies to tolerate full enteral feeds was not significantly different between the groups (median 9.5days vs 10 days). There was a significantly lower incidence of large gastric residuals and regurgitation in the treated group compared with the placebo group. The number of episodes of large gastric residuals per infant was also significantly less. No adverse effects were noted.
CONCLUSION—The routine use of cisapride in preterm infants cannot be recommended to decrease the time to establish enteral feeds. Its use may be justified for clincally significant gastric stasis or regurgitation.

     

Randomised controlled trial of growth effect of hydrocortisone in congenital adrenal hyperplasia

The influence of 15 or 25 mg/m2 of daily oral hydrocortisone with fludrocortisone 0.1 mg/day on growth and laboratory findings was evaluated in a prospective randomised crossover trial over 12 months in 26 children with 21-hydroxylase deficiency. Nine non-salt losers had fludrocortisone stopped for a further six month period. Height velocity was significantly decreased during treatment with 25 mg/m2 as compared with 15 mg/m2. This was the most sensitive indicator of corticosteroid treatment excess. A dose dependent effect upon plasma concentrations of 17-hydroxyprogesterone, testosterone, and androstenedione was found but increased values were still detected in more than half of the determinations made during the 25 mg/m2 period. Height velocity and 17-hydroxyprogesterone concentrations were positively correlated. Growth hormone response to clonidine stimulation and insulin-like growth factor-1 concentrations were both within reference values and there was no difference between treatment periods. Withdrawal of fludrocortisone did not result in any difference for the non-salt losers. It was concluded that 25 mg/m2 of hydrocortisone depressed growth in children with congenital adrenal hyperplasia, and that full suppression, or even normalisation, of plasma concentrations of 17-hydroxyprogesterone and androgens should not be considered a treatment goal, but instead an indication of corticosteroid treatment excess.     

Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea

OBJECTIVE: To evaluate the impact of zinc supplementation on the clinical course, stool weight, duration of diarrhoea, changes in serum zinc, and body weight gain of children with acute diarrhoea. DESIGN: Randomised double blind controlled trial. Children were assigned to receive zinc (20 mg elemental zinc per day) containing multivitamins or control group (zinc-free multivitamins) daily in three divided doses for two weeks. SETTING: A diarrhoeal disease hospital in Dhaka, Bangladesh. PATIENTS: 111 children, 3 to 24 months old, below 76% median weight for age of the National Center for Health Statistics standard with acute diarrhoea. Children with severe infection and/or oedema were excluded. MAIN OUTCOME MEASURES: Total diarrhoeal stool output, duration of diarrhoea, rate of weight gain, and changes in serum zinc levels after supplementation. RESULTS: Stool output was 28% less and duration 14% shorter in the zinc supplemented group than placebo (p = 0.06). There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter (less than 95% height for age), 239 v 326 g/kg (p < 0.04), and who had a lower initial serum zinc (< 14 mmol/l), 279 v 329 g/kg (p < 0.05); a shortening of mean time to recovery occurred (4.7 v 6.2 days, p < 0.04) in those with lower serum zinc. There was an increase in mean serum zinc in the zinc supplemented group (+2.4 v -0.3 mumol/l, p < 0.001) during two weeks of supplementation, and better mean weight gain (120 v 30 g, p < 0.03) at the time of discharge from hospital. CONCLUSIONS: Zinc supplementation is a simple, acceptable, and affordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished.     

Randomised controlled trial of respiratory system compliance measurements in mechanically ventilated neonates

AIM—To determine whether outcomes of neonatal mechanical ventilation could be improved by regular pulmonary function testing.
METHODS—Two hundred and forty five neonates, without immediately life threatening congenital malformations, were mechanically ventilated in the newborn period. Infants were randomly allocated to conventional clinical management (control group) or conventional management supplemented by regular measurements of static respiratory system compliance, using the single breath technique, with standardised management advice based on the results.
RESULTS—Fifty five (45%) infants in each group experienced one or more adverse outcomes. The median (quartile) durations of ventilation and oxygen supplementation were 5 (2-12) and 6 (2-34) days for the control group, and 4 (2-9) and 6 (3-36) days for the experimental group (not significant). On post-hoc secondary analysis, control group survivors were ventilated for 1269 days with a median (quartile) of 5 (2-13) days, and experimental group survivors were ventilated for 775 days with a median (quartile) duration of 3 (2-8) days (p=0.03).
CONCLUSIONS—Although primary analysis did not show any substantial benefit associated with regular measurement of static respiratory system compliance, this may reflect a type II error, and a moderate benefit has not been excluded. Larger studies are required to establish the value of on-line monitoring techniques now available with neonatal ventilators.