SPLUNC1 as a biomarker of pulmonary exacerbations in children with cystic fibrosis.

BACKGROUND: Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) is an innate defence protein that acts as an anti-microbial agent and regulates airway surface liquid volume through inhibition of the epithelial sodium channel (ENaC). SPLUNC1 levels were found to be reduced in airway secretions of adults with cystic fibrosis (CF). The potential of SPLUNC1 as a biomarker in children with CF is unknown. METHODS: We quantified SPLUNC1, interleukin-8 (IL-8) and neutrophil elastase (NE) in sputum of CF children treated with either intravenous antibiotics or oral antibiotics for a pulmonary exacerbation (PEx)s, and in participants of a prospective cohort of CF children with preserved lung function on spirometry, followed over a period of two years. RESULTS: Sputum SPLUNC1 levels were significantly lower before compared to after intravenous and oral antibiotic therapy for PEx. In the longitudinal cohort, SPLUNC1 levels were found to be decreased at PEx visits compared to both previous and subsequent stable visits. Higher SPLUNC1 levels at stable visits were associated with longer PEx-free time (hazard ratio 0.85, p = 0.04). SPLUNC1 at PEx visits did not correlate with IL-8 or NE levels in sputum or forced expiratory volume in one second (FEV1) but did correlate with the lung clearance index (LCI) (r=-0.53, p < 0.001). CONCLUSION: SPLUNC1 demonstrates promising clinometric properties as a biomarker of PEx in children with CF.

Central catheter removal timing and growth patterns in preterm infants.

BACKGROUND: Early discontinuation of total parenteral nutrition (TPN) at 100 ml/kg/day of enteral feeds, compared with 140 ml/kg/day, led to significant delay in time to regain the birth weight in very low birth weight infants (birth weight < 1500 g, VLBW). Our aim was to compare the growth of infants in relation with timing of TPN discontinuation up to 2 years corrected gestational age (CGA). METHODS: Posttrial follow-up study using review of paper medical records. Participants of the randomized controlled trial studying effect of early parenteral nutrition discontinuation on time to regain birth weight in VLBW infants were included. Growth parameters inclusive of weight, length, and occipital-frontal circumference (OFC) were collected. Z-scores were calculated at five predefined time points-birth, 0-11 weeks CGA, 12-35 weeks CGA, 36-60 weeks CGA, and 61-96 weeks CGA and compared for control and intervention groups. RESULTS: Regarding weight, we found lower mean Z-score in the intervention group between 0 and 11 weeks CGA, with larger difference in extremely low birth weight infants (birth weight < 1000 g, ELBW), but this did not reach the statistical significance. Regarding length, the same difference, slightly delayed to 35 weeks CGA was observed and reached statistical significance for ELBW infants between 12 and 35 weeks CGA. There was no difference in OFC mean Z-scores at any timepoint. CONCLUSIONS: The discontinuation of TPN at 100 ml/kg/day showed significantly lower Z-score for length in ELBW infants between 12 and 35 weeks CGA. There were no differences in Z-scores by 2 years CGA.

Reporting on data monitoring committees in neonatal randomised controlled trials is inconsistent.

AIM: To evaluate the reported use of data monitoring committees (DMCs), the frequency of interim analysis, prespecified stopping rules and early trial termination in neonatal randomised controlled trials (RCTs). METHODS: We reviewed neonatal RCTs published in four high-impact general medical journals, specifically looking at safety issues including documented involvement of a DMC, stated interim analysis, stopping rules and early trial termination. We searched all journal issues over an 11-year period (2003-2013) and recorded predefined parameters on each item for RCTs meeting inclusion criteria. RESULTS: Seventy neonatal trials were identified in four general medical journals: Lancet, New England Journal of Medicine (NEJM), British Medical Journal and Journal of American Medical Association. A total of 43 (61.4%) studies reported the presence of a DMC, 36 (51.4%) explicitly mentioned interim analysis, stopping rules were reported in 15 (21.4%) RCTs and seven (10%) trials were terminated early. The NEJM most frequently reported these parameters compared to the other three journals reviewed. CONCLUSION: While the majority of neonatal RCTs report on DMC involvement and interim analysis, there is still scope for improvement. Clear documentation of safety-related issues should be a central component of reporting in neonatal trials involving newborn infants.

Assessment of paediatric clinical audit.

Consultant paediatricians in Ireland were surveyed to evaluate their perceptions of the hospital audit environment and assess their involvement in the audit process. Eighty nine (77%) replied of whom 66 (74%) had an audit department and 23 (26%) did not. Sixteen (18%) felt their hospital was well resourced for audit and 25 (28%) felt the culture was very positive but only 1 (1%) had protected time. For 61 (69%) consultants audit was very important with 38 (43%) being very actively involved in the process. The most frequent trigger for audit was non consultant hospital doctor (NCHD) career development, cited by 77 (87%). The new Professional Competence Scheme and the National Quality and Risk Management Standards will require the deficiencies identified in this survey be addressed.