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Probiotics for Preterm Infants: A Strain-Specific Systematic Review and Network Meta-analysis.
van den Akker, CHP, van Goudoever, JB, Szajewska, H, Embleton, ND, Hojsak, I, Reid, D, Shamir, R, ,
Journal of pediatric gastroenterology and nutrition. 2018;(1):103-122
Abstract
OBJECTIVES Several randomized controlled trials (RCTs) on the use of probiotics to reduce morbidity and mortality in preterm infants have provided inconsistent results. Although meta-analyses that group all of the used strains together are suggesting efficacy, it is not possible to determine the most effective strain that is more relevant to the clinician. We therefore used a network meta-analysis (NMA) approach to identify strains with greatest efficacy. METHODS A PubMed search identified placebo-controlled or head-to-head RCTs investigating probiotics in preterm infants. From trials that recorded mortality, necrotizing enterocolitis, late-onset sepsis, or time until full enteral feeding as outcomes, data were extracted and Bayesian hierarchical random-effects models were run to construct a NMA. RESULTS Fifty-one RCTs involving 11,231 preterm infants were included. Most strains or combinations of strains were only studied in one or a few RCTs. Only 3 of 25 studied probiotic treatment combinations showed significant reduction in mortality rates. Seven treatments reduced necrotizing enterocolitis incidence, 2 reduced late-onset sepsis, and 3 reduced time until full enteral feeding. There was no clear overlap of strains, which were effective on multiple outcome domains. CONCLUSIONS This NMA showed efficacy in reducing mortality and morbidity only in a minority of the studied strains or combinations. This may be due to an inadequate number, or size, of RCTs, or due to a true lack of effect for certain species. Further large and adequately powered RCTs using strains with the greatest apparent efficacy will be needed to more precisely define optimal treatment strategies.
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Meta-analysis shows limited evidence for using Lactobacillus acidophilus LB to treat acute gastroenteritis in children.
Szajewska, H, Ruszczyński, M, Kolaček, S
Acta paediatrica (Oslo, Norway : 1992). 2014;(3):249-55
Abstract
UNLABELLED A meta-analysis of four randomised controlled trials of varying methodological quality, involving 304 children aged 1-48 months, showed that Lactobacillus acidophilus LB (LB) reduced the duration of diarrhoea in hospitalised, but not outpatient, children compared with a placebo. The chance of a cure on day three was similar in both groups, but LB increased the chance of cure on day four. CONCLUSION There is limited evidence to recommend LB for treating paediatric diarrhoea.
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Meta-analysis: Lactobacillus reuteri strain DSM 17938 (and the original strain ATCC 55730) for treating acute gastroenteritis in children.
Szajewska, H, Urbańska, M, Chmielewska, A, Weizman, Z, Shamir, R
Beneficial microbes. 2014;(3):285-93
Abstract
Lactobacillus reuteri ATCC 55730 has been shown to provide a moderate clinical effect in the treatment of acute gastroenteritis (AGE) in children. However, as the L. reuteri ATCC 55730 strain was found to carry potentially transferable resistance traits for tetracycline and lincomycin, it was replaced by a new strain, L. reuteri DSM 17938, without unwanted plasmid-borne antibiotic resistance. Bioequivalence of the two strains has been suggested. We aimed to systematically evaluate data on the effectiveness of L. reuteri DSM 17938 and the original strain, L. reuteri ATCC 55730, in the treatment of AGE in children. The Cochrane Library, MEDLINE, and EMBASE databases, reference lists, and abstract books of major scientific meetings were searched in August 2013, with no language restrictions, for relevant randomised controlled trials (RCTs). Two RCTs (n=196) that evaluated L. reuteri DSM 17938 and three RCTs (n=156) that evaluated L. reuteri ATCC 55730, which involved hospitalised children aged 3 to 60 months, met the inclusion criteria. Compared with placebo or no treatment, DSM 17938 significantly reduced the duration of diarrhoea (mean difference -32 h, 95% confidence interval (CI): -41 to -24) and increased the chance of cure on day 3 (relative risk: 3.5, 95% CI: 1.2 to 10.8, random effects model). Similar results were obtained with the original strain, L. reuteri ATCC 55730. In conclusion, in hospitalised children, use of both strains of L. reuteri reduced the duration of diarrhoea, and more children were cured within 3 days. Data from outpatients and countryspecific cost-effectiveness analyses are needed. Given the limited data and the methodological limitations of the included trials, the evidence should be viewed with caution.
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Lactobacillus reuteri DSM 17938 for managing infant colic: protocol for an individual participant data meta-analysis.
Sung, V, Cabana, MD, D'Amico, F, Deshpande, G, Dupont, C, Indrio, F, Mentula, S, Partty, A, Savino, F, Szajewska, H, et al
BMJ open. 2014;(12):e006475
Abstract
INTRODUCTION Infant colic, or excessive crying of unknown cause in infants less than 3 months old, is common and burdensome. Its aetiology is undetermined, and consensus on its management is still lacking. Recent studies suggest a possible link between infant colic and gut microbiota, indicating probiotics to be a promising treatment. However, only a few strains have been tested, and results from randomised controlled trials are conflicting. It is important to clarify whether probiotics are effective for treating infant colic in general, and to identify whether certain subgroups of infants with colic would benefit from particular strains of probiotics. METHODS AND ANALYSIS Through an individual participant data meta-analysis (IPDMA), we aim to identify whether the probiotic Lactobacillus reuteri DSM 17938 is effective in the management of infant colic, and to clarify whether its effects differ according to feeding method (breast vs formula vs combined), proton pump inhibitor exposure, and antibiotic exposure. The primary outcomes are infant crying duration and treatment success (at least 50% reduction in crying time from baseline) at 21 days postintervention. Individual participant data from all studies will be modelled simultaneously in multilevel generalised linear mixed-effects regression models to account for the nesting of participants within studies. Subgroup analyses of participant-level and intervention-level characteristics will be undertaken on the primary outcomes to assess if the intervention effect differs between certain groups of infants. ETHICS AND DISSEMINATION Approved by the Royal Children's Hospital Human Research Ethics Committee (HREC 34081). Results will be reported in a peer-reviewed journal in 2015. TRIAL REGISTRATION NUMBER PROSPERO CRD42014013210.
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Meta-analysis: Lactobacillus rhamnosus GG for abdominal pain-related functional gastrointestinal disorders in childhood.
Horvath, A, Dziechciarz, P, Szajewska, H
Alimentary pharmacology & therapeutics. 2011;(12):1302-10
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Abstract
BACKGROUND A lack of reliable treatments for abdominal pain-related functional gastrointestinal disorders prompts interest in new therapies. AIM: To evaluate systematically the effect of Lactobacillus rhamnosus GG (LGG) for treating abdominal pain-related functional gastrointestinal disorders in children. METHODS MEDLINE, EMBASE, CINAHL, the Cochrane Library, trial registries and proceedings of major meetings were searched for randomised controlled trials (RCTs) evaluating LGG supplementation in children with abdominal pain-related functional gastrointestinal disorders based on the Rome II or Rome III criteria. Risk of bias was assessed for generation of the allocation sequence, allocation concealment, blinding and follow-up. RESULTS Compared with placebo, LGG supplementation was associated with a significantly higher rate of treatment responders (defined as no pain or a decrease in pain intensity) in the overall population with abdominal pain-related functional gastrointestinal disorders (three RCTs, n = 290; risk ratio, RR 1.31, 95% CI 1.08-1.59, number needed to treat, NNT 7, 95% CI 4-22) and in the irritable bowel syndrome (IBS) subgroup (three RCTs, n = 167; RR 1.70, 95% CI 1.27-2.27, NNT 4, 95% CI 3-8). However, no difference was found in the rate of treatment responders between children with functional abdominal pain or functional dyspepsia who received placebo or LGG. The intensity of pain was significantly reduced in the overall study population and in the IBS subgroup. The frequency of pain was significantly reduced in the IBS subgroup only. CONCLUSION The use of Lactobacillus rhamnosus GG moderately increases treatment success in children with abdominal pain-related functional gastrointestinal disorders, particularly among children with IBS.
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Meta-analysis: the effects of Saccharomyces boulardii supplementation on Helicobacter pylori eradication rates and side effects during treatment.
Szajewska, H, Horvath, A, Piwowarczyk, A
Alimentary pharmacology & therapeutics. 2010;(9):1069-79
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Abstract
BACKGROUND Problems with currently recommended Helicobacter pylori eradication therapies include unsatisfactory eradication rates and/or therapy-associated side effects. AIM: To investigate the effects of Saccharomyces boulardii as supplementation to standard triple therapy on H. pylori eradication rates and therapy-associated side effects. METHODS The Cochrane Library, MEDLINE and EMBASE databases were searched in July 2010, with no language restrictions, for randomized controlled trials (RCTs); additional references were obtained from reviewed articles. RESULTS Five RCTs involving a total of 1307 participants (among them only 90 children) met the inclusion criteria. Compared with placebo or no intervention, S. boulardii given along with triple therapy significantly increased the eradication rate [four RCTs, n = 915, relative risk (RR) 1.13, 95% confidence interval (CI) 1.05-1.21] and reduced the risk of overall H. pylori therapy-related adverse effects (five RCTs, n = 1305, RR 0.46, 95% CI 0.3-0.7), particularly of diarrhoea (four RCTs, n = 1215, RR 0.47, 95% CI 0.32-0.69). There were no significant differences between groups in the risk of other adverse effects. CONCLUSION In patients with H. pylori infection, there is evidence to recommend the use of S. boulardii along with standard triple therapy as an option for increasing the eradication rates and decreasing overall therapy-related side effects, particularly diarrhoea.