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Competing Interests: The authors declare no conflicts of interest.

Background: Cystic fibrosis (CF) is a life-shortening genetic disease, yet life expectancy has recently increased, shifting the focus to disease management and health-related quality of life (HRQoL). Identification of clinical factors, such as weight status and CF-related diabetes (CFRD), that are associated with HRQoL can inform clinicians about the patient's health perception. The goal of this systematic review was two prong: identify the association of pediatric weight status and HRQoL and determine how CFRD status impacts HRQoL., Methods: A systematic review of published research was conducted following the methodology in the Cochrane Handbook on Systematic Reviews for Interventional Studies. Results were reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses. Risk of bias was assessed using the National Heart Lung & Blood Institute tool. A meta-analysis was not performed due to variability of the inclusion/exclusion criteria, differences in outcome reporting, and insufficient primary outcome data to pool., Results: Nine studies met inclusion criteria (n = 6 explored weight status and n = 3 studied CFRD), for a total of 1585 subjects (CFRD cases = 87). Pediatric weight status was positively associated with HRQoL, most commonly the Body Image and Eating Disturbance domains. CFRD was negatively associated with HRQoL, specifically the Treatment Burden and Weight domains., Conclusions: Based on the limited data available, improved pediatric weight status appears to increase HRQoL while a CFRD diagnosis appears to decrease HRQoL. More research is needed to fully understand the role of these clinical factors on HRQoL, especially with life expectancy increasing among those with CF., (© 2021 Wiley Periodicals LLC.)

Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In addition, circulating IgE impairs innate anti-viral immune responses. The latter effect could magnify the effects of another early life exposure associated with increased risk of the development of asthma - viral infections. Omalizumab binds to circulating IgE and thus ablates antigen signaling through IgE-related mechanisms. Further, it has been shown restore IFN-α response to rhinovirus and to reduce asthma exacerbations during the viral season. We therefore hypothesized that early blockade of IgE and IgE mediated responses with omalizumab would prevent the development and reduce the severity of asthma in those at high risk for developing asthma. Herein, we describe a double-blind, placebo-controlled trial of omalizumab in 2-3 year old children at high risk for development of asthma to prevent the development and reduce the severity of asthma. We describe the rationale, methods, and lessons learned in implementing this potentially transformative trial aimed at prevention of asthma., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Gastroesophageal reflux (GER) is common among infants, but when symptoms become troublesome, that is defined as gastroesophageal reflux disease (GERD). Making a diagnosis of GERD is difficult because there is no gold standard. GERD can be especially problematic for infants with cystic fibrosis (CF). There are signs and symptoms (ie, malnutrition, recurring aspiration pneumonias, refusal to eat, wheezing, coughing, and asthma) in addition to invasive and noninvasive methods used to determine a diagnosis. The treatments for GERD span from nonpharmacological to surgical, with a laparoscopic Nissen fundoplication being the gold standard of surgical intervention. Although surgical interventions have been demonstrated to reduce symptoms associated with GERD, there is little known about the weight/growth-related outcomes. This case report discusses an infant with CF and GERD requiring multiple interventions and ultimately a laparoscopic Nissen fundoplication and the weight changes from presurgery to postsurgery. The case report is expanded upon with a structured literature review of fundoplication and growth studies. There were 4 available studies that assessed changes in weight/growth before and after fundoplication among children with GERD. Because of the heterogeneity of the nutrition outcomes used, the weight/growth benefits after fundoplication are unclear at this time. Further research in needed to assess the nutrition outcomes among patients with GERD requiring fundoplication., (© 2020 American Society for Parenteral and Enteral Nutrition.)

Meropenem exposures from 15 children (8-17 years old) with cystic fibrosis (CF) acute pulmonary exacerbation were analyzed to define the pharmacodynamic threshold required for a positive response. The primary endpoint was the relative increase in forced expiratory volume in 1 s (↑FEV 1 ) between pre- and posttreatment. Meropenem pharmacodynamic indices (fT > MIC, fAUC/MIC, fC min /MIC) over the first 24 h were estimated for each participant based on their individual parameter estimates and the isolated pathogen with the highest meropenem MIC. Pseudomonas aeruginosa was the most common pathogen (n = 11/15). The mean ± SD ↑FEV 1 was 18.8% ± 11.3% posttreatment. The mean (range) fT > MIC exposure was 63% (0-100%). An E max model determined a significant relationship between fT > MIC and ↑FEV 1 (r 2 = 0.8, P < 0.0004). 65% fT > MIC was a significant predictor of response; the median (25th, 75th %) ↑FEV 1 was 28.5% (22.2%, 31.7%) in those patients who achieved above 65% fT > MIC and 7.8% (1.1%, 12.6%) in those at or below 65% fT > MIC (P = 0.001). This is the first study in CF children to link meropenem exposure with a positive response as measured by ↑FEV 1 . Larger studies are required to confirm this exposure threshold., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Meropenem is frequently used to treat pulmonary exacerbations in children with cystic fibrosis (CF) in the USA. Prolonged-infusion meropenem improves the time that free drug concentrations remain above the MIC (fT> MIC) in adults, but data in CF children are sparse. We describe the population pharmacokinetics, tolerability and treatment burden of prolonged-infusion meropenem in CF children., Methods: Thirty children aged 6-17 years with a pulmonary exacerbation received 40 mg/kg meropenem every 8 h; each dose was administered as a 3 h infusion. Pharmacokinetics were determined using population methods in Pmetrics. Monte Carlo simulation was employed to compare 0.5 with 3 h infusions to estimate the probability of pharmacodynamic target attainment (PTA) at 40% fT> MIC. NCT#01429259., Results: A two-compartment model fitted the data best with clearance and volume predicted by body weight. Clearance and volume of the central compartment were 0.41 ± 0.23 L/h/kg and 0.30 ± 0.17 L/kg, respectively. Half-life was 1.11 ± 0.38 h. At MICs of 1, 2 and 4 mg/L, PTAs for the 0.5 h infusion were 87.6%, 70.1% and 35.4%, respectively. The prolonged infusion increased PTAs to >99% for these MICs and achieved 82.8% at 8 mg/L. Of the 30 children, 18 (60%) completed treatment with prolonged infusion; 5 did so at home without any reported burden. Nine patients were changed to a 0.5 h infusion when discharged home., Conclusions: In these CF children, meropenem clearance was greater compared with published values from non-CF children. Prolonged infusion provided an exposure benefit against pathogens with MICs ≥1 mg/L, was well tolerated and was feasible to administer in the hospital and home settings, the latter depending on perception and family schedule., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The activity of ceftolozane/tazobactam was tested against 50 nonduplicate Pseudomonas aeruginosa from 18 cystic fibrosis children collected in 2012-2014. These isolates were multidrug resistant with susceptibility to meropenem, ceftazidime, and piperacillin/tazobactam of 46%, 58%, and 50%, respectively. Ceftolozane/tazobactam was the most active with MIC50, MIC90, and percent susceptibility of 2mg/L, 8 mg/L, and 86%., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A 15-week, whole-body inhalation study of the vapors of a distillate (LCCN-D) of light catalytic cracked naphtha (CAS no. 64741-55-5, LCCN) was conducted with Sprague-Dawley rats. Target exposure concentrations were 0, 750, 2500, and 7500 ppm for 6 hours/day, 5 days/week. Over the course of the study, animals received at least 65 exposures. For a portion of the control and 7500-ppm groups, a 4-week postexposure period was included in the study. Subchronic toxicity was evaluated using standard parameters. During life, neurotoxicity was evaluated by motor activity assessment and a functional observational battery. Selected tissues from animals in all exposure groups were examined microscopically. Neuropathologic examination of selected neuronal tissues from animals in the control and high-exposure groups was also conducted. No compound-related effects were seen on survival, clinical chemistry, food consumption, or physical signs. No evidence of neurotoxicity was seen at any exposure level. Slight decreases in hematocrit and hemoglobin concentrations were seen in male rats at the end of exposure to 7500 ppm LCCN-D. However, values were within normal physiological ranges and recovery occurred. Slight decreases in mean body weights and body weight gain were observed in high-exposure females during the first 7 weeks of exposure, but this decrease was not seen during the second half of the study. Male rat nephropathy involving hyaline droplet formation and alpha-2micro-globulin accumulation was seen in mid- and high-exposure males, an effect not relevant to humans. The incidence and severity of goblet cell hypertrophy/hyperplasia and respiratory epithelium hyperplasia in nasoturbinal tissues were greater in high-exposure animals, but recovery occurred. None of the effects observed were considered toxicologically significant. The no-observable-adverse-effect level (NOAEL) for subchronic and neurotoxicity of LCCN-D was > or = 7500 ppm.

The urinary excretion of 4-aminimidazole-5-carboxamide (AIC) as been reported to be increased in children with acute leukemia and has been correlated with disease status. Using a modification of the method of Skibba et al [5], determinations were made on urine from 26 children with acute leukemia. The urine from ten normal children served as controls. The effect of chemotherapy on urinary AIC was studied comparing patients on vincristine and prednisone (V+P) with those on 6-mercaptopurine, methotrexate, and cyclophosphamide (Triple Rx). Patients in remission on Triple Rx had lower levels of urinary AIC than did patients on Triple Rx in relapse or patients on V+P in either remission or relapse. Twenty patients had sequential measurements. Values for individual patients were not predictive of disease status. One such patient is described. This study demonstrates that chemotherapy, as well as disease status, affects the urinary excretion of AIC in children with acute leukemia.