Search

Background: Uncertainty remains about the role of probiotics to prevent necrotising enterocolitis (NEC) some of which arises from the variety of probiotic interventions used in different trials, many with no prior evidence of potential efficacy. Mechanistic studies of intestinal barrier function embedded in a large probiotic trial could provide evidence about which properties of probiotics might be important for NEC prevention thus facilitating identification of strains with therapeutic potential., Methods: Intestinal permeability, stool microbiota, SCFAs and mucosal inflammation were assessed from the second postnatal week in babies enrolled to a randomised controlled trial of B. breve BBG-001 (the PiPS trial). Results were compared by allocation and by stool colonisation with the probiotic., Results: Ninety-four preterm babies were recruited across six nested studies. B. breve BBG-001 content was higher by allocation and colonisation; Enterobacteriaceae and acetic acid levels were higher by colonisation. No measure of intestinal barrier function showed differences. The PiPS trial found no evidence of efficacy to reduce NEC., Conclusions: That the negative results of the PiPS trial were associated with failure of this probiotic to modify intestinal barrier function supports the possibility that the tests described here have the potential to identify strains to progress to large clinical trials., Impact: Uncertainty about the therapeutic role of probiotics to prevent necrotising enterocolitis is in part due to the wide range of bacterial strains with no previous evidence of efficacy used in clinical trials. We hypothesised that mechanistic studies embedded in a probiotic trial would provide evidence about which properties of probiotics might be important for NEC prevention. The finding that the probiotic strain tested, Bifidobacterium breve BBG-001, showed neither effects on intestinal barrier function nor clinical efficacy supports the possibility that these tests have the potential to identify strains to progress to large clinical trials.

The microbial dysbiosis associated with necrotizing enterocolitis (NEC) in preterm infants suggests that early exposure to probiotics may decrease and antibiotics may increase NEC risk. However, administration of Bifidobacterium breve strain BBG-001 to preterm infants did not affect NEC incidence in a multicenter randomised controlled phase 3 trial (PiPS trial). Using a subset of these subjects we compared the fecal microbiome of probiotic and placebo groups and assessed the impact of early antibiotic treatment. Extracted DNA from 103 fecal samples collected at 36weeks post-menstrual age underwent PCR amplification of a fragment of the 16S rRNA gene. Heatmaps were constructed showing the proportions of sequences from bacterial families present at >1% of the community. Stepwise logistic regression assessed the association between early antibiotic exposure and microbiome group. There was no difference in the microbial richness and diversity of the microbiome of preterm infants following treatment with probiotic or a placebo. Conversely, early antimicrobial exposure was associated with different patterns of colonisation, specifically a relative abundance of Proteobacteria. These findings highlight that the potential influence of probiotics on the microbiome of preterm infants remains unclear whereas the modulatory effect of antibiotic exposure on microbial colonisation requires further research., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Necrotising enterocolitis (NEC) and late-onset sepsis remain important causes of death and morbidity in preterm babies. Probiotic administration might strengthen intestinal barrier function and provide protection; this is supported by published meta-analyses, but there is a lack of large well-designed trials., Objective: To test the use of the probiotic Bifidobacterium breve strain BBG-001 to prevent NEC, late-onset sepsis and death in preterm babies while monitoring probiotic colonisation of participants., Design: Double-blind, randomised, placebo-controlled trial., Setting: Recruitment was carried out in 24 hospitals, and the randomisation programme used a minimisation algorithm. Parents, clinicians and outcome assessors were blinded to the allocation., Participants: Babies born between 23 and 30 weeks' gestation and randomised within 48 hours of birth. Exclusions included life-threatening or any gastrointestinal malformation detected within 48 hours of birth and no realistic chance of survival., Interventions: Active intervention: 1 ml of B. breve BBG-001 in one-eighth-strength infant formula Neocate(®) (Nutricia Ltd, Trowbridge, UK), (6.7 × 10(7) to 6.7 × 10(9) colony-forming units) per dose administered enterally. Placebo: 1 ml of one-eighth-strength infant formula Neocate. Started as soon as practicable and continued daily until 36 weeks' postmenstrual age., Main Outcome Measures: Primary outcomes were an episode of bloodstream infection, with any organism other than a skin commensal, in any baby between 72 hours and 46 weeks' postmenstrual age; an episode of NEC Bell stage ≥ 2 in any baby; and death before discharge from hospital. Secondary outcomes included stool colonisation with B. breve., Results: In total, 654 babies were allocated to receive probiotic and 661 to receive placebo over 37 months from July 2010. Five babies were withdrawn; 650 babies from the probiotic group and 660 from the placebo group were included in the primary analysis. Baseline characteristics were well balanced. There was no evidence of benefit for the primary outcomes {sepsis: 11.2% vs. 11.7% [adjusted relative risk (RR) 0.97, 95% confidence interval (CI) 0.73 to 1.29]; NEC Bell stage ≥ 2: 9.4% vs. 10.0% [adjusted RR 0.93, 95% CI 0.68 to 1.27]; and death: 8.3% vs. 8.5% [adjusted RR 0.93, 95% CI 0.67 to 1.30]}. B. breve colonisation status was available for 1186 (94%) survivors at 2 weeks' postnatal age, of whom 724 (61%) were positive: 85% of the probiotic group and 37% of the placebo group. There were no differences for subgroup analyses by minimisation criteria and by stool colonisation with B. breve at 2 weeks. No harms associated with the interventions were reported., Limitations: Cross-colonisation of the placebo arm could have reduced statistical power and confounded results; analyses suggest that this did not happen., Conclusions: This is the largest trial to date of a probiotic intervention. It shows no evidence of benefit and does not support routine use of probiotics for preterm infants., Future Work Recommendations: The increasing understanding of the pathogenesis of NEC and sepsis will inform the choice of probiotics for testing and better define the target population. Future Phase III trials should incorporate monitoring of the quality and viability of the intervention and colonisation rates of participants; cluster design should be considered., Trial Registration: Current Controlled Trials ISRCTN05511098 and EudraCT 2006-003445-17., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 66. See the NIHR Journals Library website for further project information.

Objectives: The objectives of this study were to characterize ESBL-producing Enterobacteriaceae present in 24 neonatal units (NNUs) in eight networks participating in a multicentre probiotic study and to test the hypothesis that specific strains would cluster within individual units and networks., Methods: We performed analysis of stool samples for the presence of ESBL-producing Enterobacteriaceae at 2 weeks post-natal age and 36 weeks post-menstrual age. ESBL-producing Enterobacteriaceae were characterized and typed using molecular methods., Results: ESBL-producing Enterobacteriaceae (n = 71) were isolated from 67/1229 (5.5%) infants from whom we received a sample at either sampling time or both sampling times, and from infants in 18 (75%) of the 24 recruiting NNUs. Thirty-three Escherichia coli, 23 Klebsiella spp. and 6 Enterobacter spp. strains were characterized. ESBL-producing E. coli were all distinguishable within individual NNUs by antibiotic resistance genotype, serogroup (O25b), phenotype, phylotype or ST. Ten of the 33 were ST131 and 9 of the 10 ST131 isolates were ciprofloxacin resistant. Seven of the 10 ST131 isolates carried genes encoding CTX-M group 1 enzymes. ST131 isolates were isolated from centres within five of the eight NNU networks. There were clusters of indistinguishable ESBL-producing Klebsiella and Enterobacter isolates associated with specific NNUs., Conclusions: Strains of E. coli ST131 were distributed across neonatal networks in the south of England. There was no evidence of clustering of clonally related ESBL-producing E. coli strains, by contrast with Klebsiella spp. and Enterobacter spp., which did cluster within units. The possibility that ESBL-producing E. coli strains are spread by vertical transmission requires further investigation., (© The Author 2016. 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 objective of this paper is to present the initial results of a study aimed at showing the feasibility of using kinematic measures to distinguish skill levels in manipulating surgical tools. Through a simulated surgical task (dissection of a mandarin orange), we acquired motor performance data from three sets of subjects representing different stages of surgical training. We computed the average lateral, axial and vertical tooltip velocities for each of the two main subtasks ('Peel Skin' and 'Detach Segment'). For each subject, we defined a 6-element vector to describe the kinematic measures extracted from the two tasks and used Principal Components Analysis (PCA) to extract the two dominant contributors to overall variability to simplify the presentation of the data to the trainer. We found that the first two principal components accounted for approximately 90% of the variance across all subjects and tasks. Moreover, the PCA plot showed good intrasubject repeatability, consistency within subjects with similar levels of training, and good separation between the subject groups. The results of this pilot study will allow us to design a future intraoperative study.

The objective of this paper is to present the development of a new modelling diagram (MCMD) to represent MIS procedures in terms of both motor and cognitive actions. Through observation and analysis of several laparoscopic cholecystectomy procedures and based on task analysis techniques, we created a diagram language composed of six primary symbols: processes, decisions, interrupt service routines (ISRs), options points and AND and OR gates. We then tested and refined them during 10 new cases until no further changes seemed necessary, we have since applied this approach to 6 laparoscopic colorectal surgeries and have found that no further symbols were necessary though the procedural representation was naturally different. This modelling diagram allowed us to represent both cognitive and motor performance aspects of surgical procedures in a unified framework and will in future allow us to assess motor performance on particular surgical tasks at particular points in the procedure (i.e., the surgical context).