Eleonora Giannetti

Effect of a Probiotic Preparation (VSL#3) on Induction and Maintenance of Remission in Children With Ulcerative Colitis

OBJECTIVES:Several probiotic compounds have shown promise in the therapy of ulcerative colitis (UC). However, a strong sustained benefit remains to be seen. Uncontrolled pilot studies suggest that a probiotic preparation (VSL#3) maintains remission in mild to moderate UC and reduces active inflammation in adult patients. Aims of our prospective, 1-year, placebo-controlled, double-blind study were to assess the efficacy of VSL#3 on induction and maintenance of remission and to evaluate the safety and tolerability of the probiotic preparation therapy in children with active UC.METHODS:A total of 29 consecutive patients (mean age: 9.8 years; range: 1.7–16.1 years; female/male: 13/16) with newly diagnosed UC were randomized to receive either VSL#3 (weight-based dose, range: 450–1,800 billion bacteria/day; n=14) or an identical placebo (n=15) in conjunction with concomitant steroid induction and mesalamine maintenance treatment. Children were prospectively evaluated at four time points: within 1 month, 2 months, 6 months, and 1 year after diagnosis or at the time of relapse. Lichtiger colitis activity index and a physicians global assessment were used to measure disease activity. At baseline, within 6 months and 12 months or at the time of relapse, all patients were assessed endoscopically and histologically.RESULTS:All 29 patients responded to the inflammatory bowel disease (IBD) induction therapy. Remission was achieved in 13 patients (92.8%) treated with VSL#3 and IBD therapy and in 4 patients (36.4%) treated with placebo and IBD therapy (P<0.001). Overall, 3 of 14 (21.4%) patients treated with VSL#3 and IBD therapy and 11 of 15 (73.3%) patients treated with placebo and IBD therapy relapsed within 1 year of follow-up (P=0.014; RR=0.32; CI=0.025–0.773; NNT=2). All 3 patients treated with VSL#3 and 6 of 11 (54.5%) patients treated with placebo relapsed within 6 months of diagnosis. At 6 months, 12 months, or at time of relapse, endoscopic and histological scores were significantly lower in the VSL#3 group than in the placebo group (P<0.05). There were no biochemical or clinical adverse events related to VSL#3.CONCLUSIONS:This is the first pediatric, randomized, placebo-controlled trial that suggests the efficacy and safety of a highly concentrated mixture of probiotic bacterial strains (VSL#3) in active UC and demonstrates its role in maintenance of remission.

The association of coeliac disease in childhood with functional gastrointestinal disorders: a prospective study in patients fulfilling Rome III criteria

Aliment Pharmacol Ther 2011; 34: 783–789

A randomized, prospective, comparison study of a mixture of acacia fiber, psyllium fiber, and fructose vs polyethylene glycol 3350 with electrolytes for the treatment of chronic functional constipation in childhood.

OBJECTIVES To compare the effectiveness of a mixture of acacia fiber, psyllium fiber, and fructose (AFPFF) with polyethylene glycol 3350 combined with electrolytes (PEG+E) in the treatment of children with chronic functional constipation (CFC); and to evaluate the safety and effectiveness of AFPFF in the treatment of children with CFC. STUDY DESIGN This was a randomized, open label, prospective, controlled, parallel-group study involving 100 children (M/F: 38/62; mean age ± SD: 6.5 ± 2.7 years) who were diagnosed with CFC according to the Rome III Criteria. Children were randomly divided into 2 groups: 50 children received AFPFF (16.8 g daily) and 50 children received PEG+E (0.5 g/kg daily) for 8 weeks. Primary outcome measures were frequency of bowel movements, stool consistency, fecal incontinence, and improvement of other associated gastrointestinal symptoms. Safety was assessed with evaluation of clinical adverse effects and growth measurements. RESULTS Compliance rates were 72% for AFPFF and 96% for PEG+E. A significant improvement of constipation was seen in both groups. After 8 weeks, 77.8% of children treated with AFPFF and 83% of children treated with PEG+E had improved (P = .788). Neither PEG+E nor AFPFF caused any clinically significant side effects during the entire course of the study period. CONCLUSIONS In this randomized study, we did not find any significant difference between the efficacy of AFPFF and PEG+E in the treatment of children with CFC. Both medications were proved to be safe for CFC treatment, but PEG+E was better accepted by children.

A Mixture of 3 Bifidobacteria Decreases Abdominal Pain and Improves the Quality of Life in Children With Irritable Bowel Syndrome: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

Goals: We assessed the efficacy of a probiotic mixture of Bifidobacterium infantis M-63, breve M-16V, and longum BB536 in improving abdominal pain (AP) and quality of life (QoL) in children with irritable bowel syndrome (IBS) and functional dyspepsia (FD). Background: AP-associated functional gastrointestinal disorders, particularly IBS and FD, are common in pediatrics, and no well-established treatment is currently available. Although probiotics have shown promising results in adults, data in children are heterogeneous. Study: Forty-eight children with IBS (median age, 11.2 y; range, 8 to 17.9 y) and 25 with FD (age, 11.6 y; range, 8 to 16.6 y) were randomized to receive either a mixture of 3 Bifidobacteria or a placebo for 6 weeks. After a 2-week “washout” period, each patient was switched to the other group and followed up for further 6 weeks. At baseline and follow-up, patients completed a symptom diary and a QoL questionnaire. AP resolution represented the primary outcome parameter. Results: In IBS, but not in FD, Bifidobacteria determined a complete resolution of AP in a significantly higher proportion of children, when compared with placebo (P=0.006), and significantly improved AP frequency (P=0.02). The proportion of IBS children with an improvement in QoL was significantly higher after probiotics than after placebo (48% vs. 17%, P=0.001), but this finding was not confirmed in FD. Conclusions: In children with IBS a mixture of Bifidobacterium infantis M-63, breve M-16V, and longum BB536 is associated with improvement in AP and QoL. These findings were not confirmed in FD subjects. Trial identifier: NCT02566876 (http://www.clinicaltrial.gov).

Subtypes of irritable bowel syndrome in children: prevalence at diagnosis and at follow-up.

OBJECTIVES To assess the prevalence of irritable bowel syndrome (IBS) subtypes in childhood at diagnosis and their changes over 1 year. STUDY DESIGN This is an observational, prospective, multicenter study. Consecutive pediatric patients with IBS, according to Rome III criteria, were enrolled over a 1-year period. Parents recorded weekly stool frequency and consistency and gastrointestinal and extraintestinal symptoms in a diary. Stool consistency was scored according to the Bristol Stool Form Scale. Children were evaluated after 2, 3, 6, and 12 months. RESULTS We enrolled 100 children with IBS (median age 9.9 years, range 4.2-16.7 years, 52 girls and 48 boys). At time of enrollment, constipation-IBS was the prevalent subtype (45%), with a prevalence of girls at 62% (P < .005); diarrhea-IBS was reported in 26% of children, with a prevalence of boys at 69% (P < .005); and alternating-IBS was described in 29% of children, without a difference between sexes. During the follow-up, 10% of patients changed their IBS subtypes at 2 months, 9% at 3 months, 7% at 6 months, and 6.3% at 12 months. Twenty-four percent of patients changed IBS subtype between the time of enrollment and 12 months. CONCLUSIONS Constipation-IBS is the prevalent subtype in children, with a higher frequency in girls. In boys, diarrhea-IBS is the most common subtype. It is important to acquire knowledge about IBS subtypes to design clinical trials that may eventually shed new light on suptype-specific approaches to this condition.

Impact of the Rome II paediatric criteria on the appropriateness of the upper and lower gastrointestinal endoscopy in children

Aliment Pharmacol Ther 2010; 32: 582–590

Altered intestinal permeability is predictive of early relapse in children with steroid‐responsive ulcerative colitis

Aim To determine if small bowel involvement at diagnosis could predict early relapse in children with ulcerative colitis.

Does cow's milk protein elimination diet have a role on induction and maintenance of remission in children with ulcerative colitis?

Aims of this study were to evaluate the efficacy of a cows milk protein (CMP) elimination diet on induction and maintenance of remission and to define association with atopy in children with ulcerative colitis (UC).

Do Children Just Grow Out of Irritable Bowel Syndrome

Objective Few data exist on natural history of irritable bowel syndrome (IBS) in children; therefore we investigated symptoms evolution over time in a cohort of children with IBS. Study design In this observational, single‐center study, we prospectively enrolled newly diagnosed children with IBS and reassessed them after 24 months. At both time points, patients completed a symptoms questionnaire, and a score of stool consistency was obtained. The therapeutic strategy adopted was also recorded. Results Eighty‐three children (age 11 years, range, 4‐16.6 years; 53 males) completed the study. Forty‐seven (56.6%) patients received no medical treatment, whereas polyethylene glycol, probiotics, and trimebutine were prescribed to 9 (10.8%), 24 (28.9%), and 3 (3.6%) subjects, respectively. Twenty‐four months after diagnosis, 48 children (57.8%) reported resolution of symptoms (P < .001), without differences between sexes (P = .35) or among IBS subtypes (P = .49). Of these, 30 (62.5%) had been only reassured and 18 (37.5%) had been prescribed medical treatment (P = .26). Despite not being statistically significant, symptoms resolution was more common in patients receiving no medical treatment than in those receiving probiotics (63.8% vs 41.6%, P = .08). Among patients with constipation‐IBS, no difference was found in symptoms resolution between patients receiving polyethylene glycol and those receiving no medical treatment (67% and 40%, respectively, P = 1). Conclusions Children with IBS are likely to show spontaneous symptoms resolution over a 24‐month follow‐up, regardless of sex, age, impact of symptoms on daily activities, and IBS subtypes.

Periappendiceal inflammation in pediatric ulcerative colitis.

Background: An involvement of the appendiceal orifice as a distintive skip lesion in adults with left side ulcerative colitis (UC) has been reported. The aim of our prospective study was to evaluate, by endoscopy and histology, the prevalence of periappendiceal inflammation (PAI) in children affected by UC. Methods: Fifty of 77 consecutive children undergoing total colonoscopy, who had a diagnosis of UC not extended beyond the hepatic flexure were enrolled. Results: PAI was endoscopically present in 16 of 50 patients (32%) with UC. Patients were divided in 2 groups: group A included the 16 patients with PAI, whereas group B included 34 patients without PAI. We found that among the 2 groups, PAI was more frequent in patients with new diagnosis than in those with pre-existing UC (P = 0.016). At index colonoscopy, the patients of group A had a significant major extent of disease (P = 0.013). Moreover, the histologic grade of inflammation at the ascending colon was significantly higher in group A than in group B (P = 0.014). Clinical activity, measured by pediatric ulcerative colitis activity index, and use of medication did not show significant differences among groups (P = 0.464 and P = 0.723, respectively). The use of immunosuppressant was significantly higher in group A than in group B. Conclusions: PAI is a frequent skip lesion in children with UC. It seems more frequent in patients with new diagnosis, and it is associated with a major extent of the disease and with a higher grade of histologic inflammation at the ascending colon.