Cow's milk allergy guidelines: a quality appraisal with the AGREE II instrument.

BACKGROUND: The appropriate diagnosis and management of cow's milk allergy (CMA) is challenging. OBJECTIVE: To systematically review the quality of the existing guidelines on CMA. METHODS: The Cochrane Library, MEDLINE, and EMBASE databases were searched from 2010 to November 2015. The methodological rigour, quality, and transparency of relevant guidelines were assessed with the use of the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. RESULTS: Of the 15 included guidelines, two, both developed by recognized scientific organizations, achieved the highest score (100%). Eight others were considered to be of high quality (i.e., overall quality scores >60%). The quality scores for each domain varied. Of all the domains, clarity and presentation had the highest mean score, and applicability had the lowest mean score. The scores (mean ± SD) for individual domains were as follows: domain 1 (score and purpose) 62 ± 36%; domain 2 (stakeholder involvement) 56 ± 33%; domain 3 (rigor of development) 55 ± 38%; domain 4 (clarity of presentation) 71 ± 29%; domain 5 (applicability) 44 ± 33%; and domain 6 (editorial independence) 60 ± 36%. One guideline had the maximum possible score of 100% for all AGREE II domains. CONCLUSION AND CLINICAL RELEVANCE: A number of guidelines on CMA are available; however, their quality varies. Overall, the guidelines developed by recognized professional/scientific organizations were of the highest quality. These guidelines should be recommended for use. Still, the methodological quality of CMA guidelines may be improved.

Meta-analysis: sequential therapy for Helicobacter pylori eradication in children.

BACKGROUND: Problems with the standard triple treatment recommended for Helicobacter pylori eradication therapy include unsatisfactory (less than 80%) eradication rates among children. AIM: To assess the evidence for sequential therapy compared with triple therapy on H. pylori eradication rates in children. METHODS: The Cochrane Library, MEDLINE and EMBASE databases were searched in May 2012, with no language restrictions, as were abstracts from major gastroenterology conferences, for randomised controlled trials (RCTs) comparing sequential therapy with standard triple therapy for H. pylori eradication. Additional references were obtained from reviewed articles. Authors were contacted for extra information. Dichotomous data were pooled to obtain the relative risk (RR) of the eradication rate, with a 95% CI. RESULTS: Ten RCTs involving a total of 857 children aged 3-18 years met the inclusion criteria. Of the 409 patients in the sequential therapy group, 318 (78%, 95% CI 73-82) experienced eradication compared with 314 of the 444 patients (71%, 95% CI 66-75) in the standard triple therapy group (RR 1.14, 95% CI 1.06-1.23, number needed to treat 15; fixed-effects model). Sequential therapy was superior to 7-day standard triple therapy, but was not significantly better than 10-day or 14-day triple therapy. There were no significant differences between groups in the risk of adverse effects. CONCLUSIONS: The pooled evidence suggests that 10-day sequential therapy compared with standard triple therapy may be considered as an option for increasing the eradication rates in children; however, it is still less than desired.

Meta-analysis: Lactobacillus rhamnosus GG for abdominal pain-related functional gastrointestinal disorders in childhood.

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.

Are treatment targets for hypercholesterolemia evidence based? Systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: Search for evidence supporting target age, level of intervention and target values for low-density lipoprotein (LDL) cholesterol levels in children with familial hypercholesterolemia. DESIGN: Systematic review and meta-analysis. PubMed, Medline, CINAHL and Cochrane Reviews databases from 1966 to 2007 were searched for articles reporting statin therapy in children and adolescents aged 8-18 years. Retrieved articles were screened for double-blind randomised controlled trials (RCTs). RESULTS: Seven trials involving 884 patients met inclusion criteria. Meta-analysis findings showed significantly reduced total cholesterol, LDL cholesterol and apolipoprotein B, whereas high-density lipoprotein cholesterol and apolipoprotein A1 were significantly increased by statin therapy. Evidence on target level in children was limited to one study attainment of LDL cholesterol treatment target in 60% of the subjects in the treatment group and none in the placebo group reached their target LDL cholesterol. Evidence on the effect of statins on surrogate markers of atherosclerosis was limited to two studies (one RCT on the effect upon the carotid intima-media thickness (n=211; mean difference (MD) -0.01; 95% CI -0.03 to -0.00), and one showing that the mean absolute change in flow-mediated dilation after 28 weeks of statin treatment was significantly higher in the simvastatin group compared to placebo group (MD 2.7%; 95% CI 0.42 to 4.98). CONCLUSIONS: There is no firm evidence regarding when to start statin treatment or what target LDL cholesterol level should be attained. Recent recommendations that favour statins as the first-line drug treatment for hypercholesterolemia are evidence based. Studying high-risk groups (obese or diabetic patients) and incorporating composite end points may help define treatment guidelines.

Meta-analysis: enteral nutrition in active Crohn's disease in children.

BACKGROUND: Controversy exists surrounding the optimal treatment for inducing remission in active Crohn's disease. AIM: To review and update evidence on the effectiveness of enteral nutrition (EN) in treating active Crohn's disease in children. METHODS: MEDLINE, EMBASE and The Cochrane Library (up to February 2007) were searched for randomized controlled trials (RCTs) relevant to Crohn's disease and EN in children. RESULTS: We included 11 RCTs (n = 394). Seven RCTs (n = 204) compared EN with corticosteroid therapy. On the basis of pooled results of four RCTs (n = 144), we found no significant difference in the remission rates between groups (relative risk, RR 0.97, 95% CI 0.7-1.4, random effect model). Four RCTs (n = 190) compared two EN regimens. One of the four RCTs (n = 50) revealed a significant increase in the percentage of patients achieving remission in the total EN group compared with the partial EN group (RR 2.7, 95% CI 1-7.4). Because of lack of data, formal pooling of results was not possible for many outcomes (e.g., time until remission, duration of remission, growth data). CONCLUSIONS: Limited data suggest similar efficacy for EN and corticosteroids. As the number of patients needed to provide a definite answer is too large, future studies should focus on detailed outcome measurements including growth and quality of life.

A randomized double-blind placebo-controlled trial of Lactobacillus GG for abdominal pain disorders in children.

BACKGROUND: Functional abdominal pain disorders (FAPD) are common in school-aged children; however, there is no reliable treatment. AIM: To determine the efficacy of Lactobacillus rhamnosus GG (LGG) for treating FAPD in children. METHODS: A total of 104 children who fulfilled the Rome II criteria for functional dyspepsia (FD), or irritable bowel syndrome (IBS), or functional abdominal pain (FAP) were enrolled in a double-blind, randomized controlled trial in which they received LGG (n = 52), or placebo (n = 52) for 4 weeks. RESULTS: For the overall study population, those in the LGG group were more likely to have treatment success (no pain) than those in the placebo group (25% vs. 9.6%, relative benefit (RB) 2.6, 95% confidence interval (CI): 1.05-6.6, number needed to treat (NNT) 7, 95% CI: 4-123). For children with IBS (n = 37), those in the LGG group were more likely to have treatment success than those in the placebo group (33% vs. 5%, RB 6.3, 95% CI: 1.2-38, NNT 4, 95% CI: 2-36) and reduced frequency of pain (P = 0.02), but not pain severity (P = 0.10). For the FD group (n = 20) and FAP group (n = 47), no differences were found. CONCLUSION: The LGG appears to moderately increase treatment success, particularly among children with IBS.

Meta-analysis: Smectite in the treatment of acute infectious diarrhoea in children.

BACKGROUND: Although not currently recommended, dioctahedral smectite (smectite) is commonly used to treat acute infectious diarrhoea in many countries. AIM: To evaluate systematically the effectiveness of smectite in treating acute infectious diarrhoea in children. METHODS: Using medical subject headings and free-language terms, the following electronic databases were searched for studies relevant to acute infectious diarrhoea and smectite: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized-controlled trials were included. RESULTS: Nine randomized-controlled trials (1238 participants) met the inclusion criteria. Combined data from six randomized-controlled trials showed that smectite significantly reduced the duration of diarrhoea compared with placebo. The pooled weighted mean difference was (-22.7 h, 95% CI: -24.8 to -20.6) with a fixed model and remained significant in a random effect model (-24.4 h, 95% CI: -29.8 to -19.1). The chance of cure on intervention day 3 was significantly increased in the smectite vs. the control group (RR 1.64, 95% CI: 1.36-1.98; number needed to treat 4, 95% CI: 3-5). Adverse effects were similar in both groups. CONCLUSIONS: Smectite may be a useful adjunct to rehydration therapy in treating acute paediatric gastroenteritis. However, the results of this meta-analysis should be interpreted with caution as most of the included studies had important limitations. Cost-effectiveness analyses should be undertaken before routine pharmacological therapy with smectite is recommended.