John Stevens

Sequential ciprofloxacin therapy in pediatric cystic fibrosis : comparative study vs. ceftazidime/tobramycin in the treatment of acute pulmonary exacerbations

BACKGROUNDnCystic fibrosis patients have chronic bacterial infections of the respiratory tract, most commonly Pseudomonas aeruginosa. Although controversial, administration of antibiotic therapy during acute pulmonary exacerbations is standard practice. Fluoroquinolones are currently not indicated for use in young children because of the observation of arthropathy and damage to growing cartilage in beagle puppies. Because of its activity against P. aeruginosa and excellent oral bioavailability, ciprofloxacin offers a unique therapeutic alternative for this patient population.nnnOBJECTIVEnThis prospective, randomized, double blind study compared the efficacy and safety of sequential intravenous/oral ciprofloxacin vs. ceftazidime/tobramycin in hospitalized pediatric cystic fibrosis patients with an acute pulmonary exacerbation associated with P. aeruginosa infection.nnnMETHODSnOne hundred thirty patients (ages 5 to 17 years) were randomized to receive either i.v. ciprofloxacin 10 mg/kg every 8 h for 7 days followed by oral ciprofloxacin 20 mg/kg every 12 h for a minimum of 3 days or i.v. ceftazidime 50 mg/kg every 8 h plus i.v. tobramycin 3 mg/kg every 8 h for a minimum of 10 days. Clinical, bacteriologic and safety responses were assessed throughout the study.nnnRESULTSnAll 84 patients (median age, 11 years; range, 5 to 17 years) valid for efficacy in both treatment groups demonstrated clinical improvement. Five patients experienced clinical relapses (3 ciprofloxacin, 2 ceftazidime/tobramycin) by the 2- to 4-week follow-up. Intent-to-treat analysis demonstrated similar clinical findings between the two treatment groups at both the end of therapy and follow-up. Clinical improvement correlated with improvement in pulmonary function studies and the acute clinical scoring system but not with bacteriologic eradication of Pseudomonas. DNA profiles demonstrated that irrespective of colony morphology, usually one clonal strain was associated with each patients pulmonary exacerbation. Treatment-associated musculoskeletal events occurred with equal frequency (22% vs. 21%) in both study drug groups (n = 129), and arthralgias were within the range of rates for cystic fibrosis arthropathy. None of these events required study drug discontinuation.nnnCONCLUSIONnSequential i.v./oral ciprofloxacin monotherapy offers a safe and efficacious alternative to standard parenteral therapy for acute pulmonary exacerbations in pediatric cystic fibrosis patients.

Anterior pericardial tracheoplasty for congenital tracheal stenosis: Intermediate to long-term outcomes

BACKGROUNDnAlthough several techniques for the treatment of long-segment stenosis of the trachea have been reported, including slide tracheoplasty, rib grafting, and use of a pericardial patch, the optimal repair remains controversial because of a lack of midterm to long-term follow-up data.nnnMETHODSnTo assess the intermediate and long-term outcomes of patients having repair with anterior pericardial tracheoplasty, we reviewed case histories of 12 patients (1984 to present). The median age was 6.7 months (range, 1 to 98 months), and the median weight was 6.0 kg (range, 0.97 to 42 kg). All patients underwent anterior pericardial tracheoplasty through a median sternotomy during partial normothermic cardiopulmonary bypass. An average of 13 tracheal rings (range, five to 23) were divided anteriorly, and a patch of fresh autologous pericardium was used to enlarge the trachea by 1.5 times the predicted diameter for patient age and weight.nnnRESULTSnThere was one hospital death, and all but 2 patients are long-term survivors. All but 1 current survivor remain asymptomatic, with no bronchoscopic evidence of airway obstruction or granulation on the pericardial patch. All survivors examined have normal tracheal growth and development, with a median follow-up of 5.5 years (range, 1 to 11 years).nnnCONCLUSIONSnAnterior pericardial tracheoplasty for congenital tracheal stenosis provides excellent results at intermediate to long-term follow-up.

Neonatal Cochlear Function: Measurement after Exposure to Acoustic Noise during in Utero MR Imaging

PURPOSEnTo establish whether fetal exposure to the operating noise of 1.5-T magnetic resonance (MR) imaging is associated with cochlear injury and subsequent hearing loss in neonates.nnnMATERIALS AND METHODSnThe study was performed with local research ethics committee approval and written informed parental consent. Neonatal hearing test results, including otoacoustic emission (OAE) data, were sought for all neonates delivered in Sheffield who had previously undergone in utero MR imaging between August 1999 and September 2007. The prevalence of hearing impairment in these neonates was determined, with corresponding 95% confidence intervals calculated by using the binomial exact method, and mean OAE measurements were compared with anonymized local audiometric reference data by using the t test.nnnRESULTSnOne hundred three neonates who had undergone in utero MR imaging were identified; 96 of them had completed hearing screening assessment. Thirty-four of these babies were admitted to the neonatal intensive care unit (NICU), and one of them had bilateral hearing impairment. The prevalence of hearing impairment was 1% (one of 96; 95% confidence interval: 0.03%, 5.67%), which is in accordance with the prevalence expected, given the high proportion of babies in this study who had been in the NICU (ie, NICU graduates). In addition, for the well babies, there was no significant difference in mean OAE cochlear response compared with that for a reference data set of more than 16,000 OAE results. When NICU graduates were included in the comparison, a significant difference (P = .002) was found in one of four frequency bands used to analyze the cochlear response; however, this difference was small compared with the normal variation in OAE measurements.nnnCONCLUSIONnThe findings in this study provide some evidence that exposure of the fetus to 1.5-T MR imaging during the second and third trimesters of pregnancy is not associated with an increased risk of substantial neonatal hearing impairment.

Pancreatic enzyme supplementation in cystic fibrosis patients before and after fibrosing colonopathy.

BACKGROUNDnIn 1994 we cared for nine cystic fibrosis patients with fibrosing colonopathy. To evaluate the relationship between fibrosing colonopathy and supplemental pancreatic enzymes we reviewed our dosing of enzymes prior to fibrosing colonopathy development and then evaluated the subsequent effect of drastically reducing pancreatic enzyme dose.nnnMETHODSnWe retrospectively reviewed pancreatic enzyme dosing for 267 cystic fibrosis patients with pancreatic insufficiency. The supplemental enzyme history of nine patients with fibrosing colonopathy was contrasted with the history of 258 nonaffected patients. The pancreatic enzyme doses of 75 patients taking at least 6,000 U lipase/kg/meal were systematically reduced to approximately 2,000 lipase units/kg/meal. We evaluated the effect of this dose reduction on change in height and weight z scores one year after achievement of stable enzyme dose.nnnRESULTSnIn the year prior to diagnosis patients with fibrosing colonopathy took a significantly larger pancreatic enzyme dose, whether assessed by highest dose or cumulative dose, than did nonaffected patients. Similar results were observed after controlling for sex and age. All 75 patients on at least 6,000 U lipase/kg/meal were able to tolerate a significant reduction in dose while achieving clinically acceptable nutrient absorption, with no change over one year in height and weight z scores.nnnCONCLUSIONSnOur data demonstrate a strong relationship between very high doses of pancreatic enzyme supplementation and formation of fibrosing colonopathy. These very high doses do not appear to be needed for adequate nutrient absorption and growth.

Lower respiratory illness in infants and young children with cystic fibrosis

The purpose of our study was to assess the effect on pulmonary function of adding intravenous hydrocortisone to the standard treatment of infants with cystic fibrosis (CF) hospitalized for lower respiratory illnesses (LRI). Twenty CF infants were randomized and received 10 days of hydrocortisone (10 mg/kg/day) or placebo in addition to standard treatment with intravenous antibiotics, chest physiotherapy, and an aerosolized‐agonist with cromolyn. Functional residual capacity (FRC) and forced expiratory flows (V′max, FRC) were measured on admission, on Day 10 of hospitalization, and as outpatients 1–2 months following hospital discharge. Pulmonary function values were adjusted for differences in body length and expressed as Z‐scores.

Specificity and sensitivity of methacholine challenge test in children with normal and hyperreactive airways

ABSTRACT. To assess the ability of the methacholine challenge test for separation between normals and patients with clinically apparent mild airway hyperreactivity, the provocative dose of inhaled methacholine required to cause a 20% drop in the forced expiratory volume in one second was evaluated in two selected pediatric populations. On the basis of a standardized respiratory questionnaire, 70 subjects, 4‐16 years of age were identified. Included were 49 normal individuals, and 21 individuals with mild airway hyperreactivity who responded to broncho‐dilators. Methacholine inhalation challenges were performed by use of a standard inhalation procedure. Forty‐seven percent of the normals (23/49) had a positive methacholine challenge test while 24% (5/21) of the patients with hyperreactive airways had a negative test by the standard criteria. A wide spectrum of specificity and sensitivity of methacholine challenge was obtained at different doses of methacholine. The greater the sensitivity, the lower the specificity. Therefore, we postulate that the methacholine challenge test can be helpful in making the clinical diagnosis but it does not allow a clear and perfect separation between normal and clinically apparent mildly airway reactive patients in a pediatric age population.

Neuropathy and vasculopathy in colonic strictures from children with cystic fibrosis.

Colonic strictures are rare in patients who have cystic fibrosis, but recently have developed in those who have been treated with delayed-release high-dose pancreatic enzyme supplements. Colonic strictures from eight such pediatric patients showed neural abnormalities consisting of ganglion cell hyperplasia and ectopia, and intermyenteric plexus hyperplasia. Cholinergic and adrenergic stains of mucosal nerve fibers were more prominent in histological sections of the cystic fibrosis strictures than in sections from colons of children without cystic fibrosis. The mean grade of staining with acetylcholinesterase in the lamina propria of the strictured cystic fibrosis colons was 2.38 +/- 1.25, compared with .93 +/- .93 (P < .055) in bowels from children without cystic fibrosis. The mean grade for tyrosine hydroxylase staining in the lamina propria was 2 +/- .97 in the strictures and was .79 +/- .81 (P < .05) in the bowels of children who did not have cystic fibrosis. Vasoactive intestinal peptide staining in bowels from children with cystic fibrosis with and without stricture did not differ significantly from that of children without cystic fibrosis. Vasculopathy consisting of fibrointimal hyperplasia in submucosal veins and mesenteric arteries was found only in colonic strictures owing to cystic fibrosis. Colonic strictures in patients with cystic fibrosis who received high-dose pancreatic enzyme supplements contain ganglion cell abnormalities, and mucosal cholinergic and adrenergic activity may be increased in these strictures. The stricture vasculopathy may be drug-related and/or related to increased catecholamine activity.

Increased Fat Absorption from Enteral Formula Through an In-line Digestive Cartridge in Patients with Cystic Fibrosis

Objectives: Supplemental enteral nutrition (EN) is used by approximately 12% of people with cystic fibrosis (CF). The objective of this study was to evaluate the safety, tolerability, and fat absorption of a new in-line digestive cartridge (Relizorb) that hydrolyzes fat in enteral formula provided to patients with CF. Methods: Patients with CF receiving EN participated in a multicenter, randomized, double-blind, crossover trial with an open-label safety evaluation period. Plasma omega-3 fatty acid (FA) concentrations were measured and used as markers of fat absorption. Gastrointestinal symptoms were recorded to evaluate safety and tolerability. Information regarding the effect of EN on appetite and breakfast consumption was also collected. Results: Before study entry, participants had received EN for a mean of 6.6 years at a mean volume of approximately 800u200amL, yet had a mean body mass index of only 17.5u200akg/m2 and omega-3 FA plasma concentrations were only 60% of levels found in normal healthy subjects. Compared with placebo, cartridge use resulted in a statistically significant 2.8-fold increase in plasma omega-3 FA concentrations. There were no adverse experiences associated with cartridge use, and a decrease in the frequency and severity of most symptoms of malabsorption was observed with cartridge use. Participants reported increased preservation of appetite and breakfast consumption with cartridge use compared with their pre-study regimen. Conclusions: Use of this in-line digestive cartridge was safe and well tolerated, and resulted in significantly increased levels of plasma omega-3 FA used with enteral formula, suggesting an overall increased fat absorption.

Multifaceted quality improvement initiative to decrease pediatric asthma readmissions

ABSTRACT Background: Asthma is the most common chronic disease of childhood and a leading cause of hospitalization in children. A primary goal of asthma control is prevention of hospitalizations. A hospital admission is the single strongest predictor of future hospital admissions for asthma. The 30-day asthma readmission rate at our institution was significantly higher than that of other hospitals in the Childrens Hospital Association. As a result, a multifaceted quality improvement project was undertaken with the goal of reducing the 30-day inpatient asthma readmission rate by 50% within two years. Methods: Analysis of our institutions readmission patterns, value stream mapping of asthma admission, discharge, and follow-up processes, literature review, and examination of comparable successful programs around the United States were all utilized to identify potential targets for intervention. Interventions were implemented in a stepwise manner, and included increasing inhaler availability after discharge, modifying asthma education strategies, and providing in-home post-discharge follow-up. The primary outcome was a running 12-month average 30-day inpatient readmission rate. Secondary outcomes included process measures for individual interventions. Results: From a peak of 7.98% in January 2013, a steady decline to 1.65% was observed by July 2014, which represented a 79.3% reduction in 30-day readmissions. Conclusion: A significant decrease in hospital readmissions for pediatric asthma is possible, through comprehensive, multidisciplinary quality improvement that spans the continuum of care.

Malassezia Pneumonia: A Rare Complication of Parenteral Nutrition Therapy.

Malassezia species (formerly known as Pityrosporum) are part of normal human skin flora and have been associated with benign dermatologic conditions, such as seborrheic dermatitis and tinea versicolor. In rare cases, however, Malassezia has been associated with systemic disease in immunocompromised patients and infants in the neonatal intensive care unit. Malassezia species require long-chain fatty acids for growth and therefore have a known predilection for individuals receiving lipid containing intravenous parenteral nutrition (PN). Systemic infections are characterized by prolonged fevers and illness but can include nonspecific signs and symptoms. We present the diagnosis and management of a rare case of an immunocompetent, nonneonatal, PN-dependent child with Malassezia furfur pneumonia.