Respiratory syncytial virus and recurrent wheeze in healthy preterm infants.

BACKGROUND: Respiratory syncytial virus (RSV) infection is associated with subsequent recurrent wheeze. Observational studies cannot determine whether RSV infection is the cause of recurrent wheeze or the first indication of preexistent pulmonary vulnerability in preterm infants. The monoclonal antibody palivizumab has shown efficacy in preventing severe RSV infection in high-risk infants. METHODS: In the double-blind, placebo-controlled MAKI trial, we randomly assigned 429 otherwise healthy preterm infants born at a gestational age of 33 to 35 weeks to receive either monthly palivizumab injections (214 infants) or placebo (215 infants) during the RSV season. The prespecified primary outcome was the total number of parent-reported wheezing days in the first year of life. Nasopharyngeal swabs were taken during respiratory episodes for viral analysis. RESULTS: Palivizumab treatment resulted in a relative reduction of 61% (95% confidence interval, 56 to 65) in the total number of wheezing days during the first year of life (930 of 53,075 days in the RSV-prevention group [1.8%] vs. 2309 of 51,726 days [4.5%] in the placebo group). During this time, the proportion of infants with recurrent wheeze was 10 percentage points lower in patients treated with palivizumab (11% vs. 21%, P=0.01). CONCLUSIONS: In otherwise healthy preterm infants, palivizumab treatment resulted in a significant reduction in wheezing days during the first year of life, even after the end of treatment. These findings implicate RSV infection as an important mechanism of recurrent wheeze during the first year of life in such infants. (Funded by Abbott Laboratories and by the Netherlands Organization for Health Research and Development; MAKI Controlled Clinical Trials number, ISRCTN73641710.).

Multi-center randomized controlled trial of cognitive treatment, placebo, oxybutynin, bladder training, and pelvic floor training in children with functional urinary incontinence.

OBJECTIVE: Functional urinary incontinence causes considerable morbidity in 8.4% of school-age children, mainly girls. To compare oxybutynin, placebo, and bladder training in overactive bladder (OAB), and cognitive treatment and pelvic floor training in dysfunctional voiding (DV), a multi-center controlled trial was designed, the European Bladder Dysfunction Study. METHODS: Seventy girls and 27 boys with clinically diagnosed OAB and urge incontinence were randomly allocated to placebo, oxybutynin, or bladder training (branch I), and 89 girls and 16 boys with clinically diagnosed DV to either cognitive treatment or pelvic floor training (branch II). All children received standardized cognitive treatment, to which these interventions were added. The main outcome variable was daytime incontinence with/without urinary tract infections. Urodynamic studies were performed before and after treatment. RESULTS: In branch I, the 15% full response evolved to cure rates of 39% for placebo, 43% for oxybutynin, and 44% for bladder training. In branch II, the 25% full response evolved to cure rates of 52% for controls and 49% for pelvic floor training. Before treatment, detrusor overactivity (OAB) or pelvic floor overactivity (DV) did not correlate with the clinical diagnosis. After treatment these urodynamic patterns occurred de novo in at least 20%. CONCLUSION: The mismatch between urodynamic patterns and clinical symptoms explains why cognitive treatment was the key to success, not the added interventions. Unpredictable changes in urodynamic patterns over time, the response to cognitive treatment, and the gender-specific prevalence suggest social stress might be a cause for the symptoms, mediated by corticotropin-releasing factor signaling pathways.

Urethral meatus deformities in girls as a factor in dysfunctional voiding.

PURPOSE: Girls with an anterior deflected urinary stream (ADUS) cannot void in the ideal toileting position, resulting in lower success rates of behavioral training programs. Purpose was to study prospectively the clinical effects of surgical meatus correction for ADUS in girls with dysfunctional voiding (DV). METHODS: A cohort of 171 DV patients aged 6-12 years was investigated. All had recurrent urinary tract infections (UTIs), staccato or interrupted uroflow, and >10% residual urine on ultrasound. For study purposes, all underwent a urodynamic study (UDS) to confirm DV. ADUS was recognized at first examination in 55 patients (32%) and a dorsally directed meatal correction was performed to achieve a normal direction of the urinary stream. The non-ADUS group (116 girls) was given behavioral therapy (BT); however, a subgroup of 11 girls with ADUS was detected with persistent complaints after failed BT. These 11 girls also underwent a meatal correction. RESULTS: All DV complaints were resolved in 25 of the 55 (45%) girls from the original ADUS group and 8 of the 11 (73%) girls from the second group. During UDS, in the ADUS group free of complaints after meatal correction, a significantly higher P(max) (102 cmH(2) O) was found compared to those who did not benefit from correction (P(max) 76 cmH(2)O). CONCLUSION: In this study, 39% of female DV patients had ADUS complaints. After surgical correction, 50% were free of all complaints without requiring any further behavioral training. The fast recovery into a normal voiding pattern in these girls shows that a meatus deformity needs to be looked for in all girls presenting with DV.

Antibiotic prophylaxis for urinary tract infections in children with spina bifida on intermittent catheterization.

PURPOSE: Antibiotic prophylaxis (low dose chemoprophylaxis) has been prescribed since the introduction of clean intermittent catheterization in children with spina bifida. We hypothesized that stopping low dose chemoprophylaxis does not increase the number of urinary tract infections in these patients. MATERIALS AND METHODS: A total of 176 patients with spina bifida participated in a randomized controlled trial (ISRCTN trial number 56278131) of either continuation or discontinuation of low dose chemoprophylaxis. During the 18-month study period biweekly urine samples were evaluated for leukocyturia and bacteriuria with dipsticks and cultures. Asymptomatic significant bacteriuria (positive culture results without clinical symptoms) and urinary tract infections (significant bacteriuria with clinical symptoms and leukocyturia) were analyzed. RESULTS: Discontinuation of low dose chemoprophylaxis resulted in higher rates of asymptomatic significant bacteriuria (incidence rate ratio 1.23, 95% CI 1.08-1.40, p = 0.002) and urinary tract infection (IRR 1.44, 95% CI 1.13-1.83, p = 0.003). For urinary tract infection the number needed to harm was 2.2, that is if 2 patients discontinued low dose chemoprophylaxis for a year, 1 extra urinary tract infection would result. Febrile urinary tract infection occurred once in every 30 patient-years and slightly more often in the discontinuation group (relative risk 2.0, 95% CI 0.38-10.6, p = 0.4). Of 88 patients allocated to discontinuation of low dose chemoprophylaxis 38 (43%) switched back to chemoprophylaxis. The urinary tract infection rate was nonsignificantly higher in the presence of vesicoureteral reflux. Male gender and a low pre-study rate of urinary tract infection predicted successful discontinuation. CONCLUSIONS: Patients with spina bifida on clean intermittent catheterization and antibiotic prophylaxis for urinary tract infections can safely discontinue this prophylaxis, in particular males, patients with low urinary tract infection rates and patients without vesicoureteral reflux.

Urinary tract infections in children with spina bifida: an inventory of 41 European centers.

The introduction of clean intermittent catheterization (CIC) in 1972 and low-dose chemoprophylaxis (LDCP, antibiotic prophylaxis), anticholinergic medication and urological surgery in the mid-1980s has improved the long-term outcome of renal function in children with neurogenic bladder sphincter dysfunction (NBSD) due to spina bifida (SB). We have conducted a European survey of the protocols for diagnosing and treating urinary tract infections (UTIs) in these children, using a web-based questionnaire. The responses from 41 centers in 14 European countries confirm that although most centers have standardized protocols for treating UTIs, there is no consensus among European centers in terms of protocols for preventing, diagnosing and treating UTIs in children with NBSD and for CIC.