Sequential versus standard triple first-line therapy for Helicobacter pylori eradication.

BACKGROUND: Non-bismuth quadruple sequential therapy (SEQ) comprising a first induction phase with a dual regimen of amoxicillin and a proton pump inhibitor (PPI) for five days followed by a triple regimen phase with a PPI, clarithromycin and metronidazole for another five days, has been suggested as a new first-line treatment option to replace the standard triple therapy (STT) comprising a proton pump inhibitor (PPI), clarithromycin and amoxicillin, in which eradication proportions have declined to disappointing levels. OBJECTIVES: To conduct a meta-analysis of randomised controlled trials (RCTs) comparing the efficacy of a SEQ regimen with STT for the eradication of H. pylori infection, and to compare the incidence of adverse effects associated with both STT and SEQ H. pylori eradication therapies. SEARCH METHODS: We conducted bibliographical searches in electronic databases, and handsearched abstracts from Congresses up to April 2015. SELECTION CRITERIA: We sought randomised controlled trials (RCTs) comparing 10-day SEQ and STT (of at least seven days) for the eradication of H. pylori. Participants were adults and children diagnosed as positive for H. pylori infection and naïve to H. pylori treatment. DATA COLLECTION AND ANALYSIS: We used a pre-piloted, tabular summary to collect demographic and medical information of included study participants as well as therapeutic data and information related to the diagnosis and confirmatory tests.We evaluated the difference in intention-to-treat eradication between SEQ and STT regimens across studies, and assessed sources of the heterogeneity of this risk difference (RD) using subgroup analyses.We evaluated the quality of the evidence following Cochrane standards, and summarised it using GRADE methodology. MAIN RESULTS: We included 44 RCTs with a total of 12,284 participants (6042 in SEQ and 6242 in STT). The overall analysis showed that SEQ was significantly more effective than STT (82% vs 75% in the intention-to-treat analysis; RD 0.09, 95% confidence interval (CI) 0.06 to 0.11; P < 0.001, moderate-quality evidence). Results were highly heterogeneous (I² = 75%), and 20 studies did not demonstrate differences between therapies.Reporting by geographic region (RD 0.09, 95% CI 0.06 to 0.12; studies = 44; I² = 75%, based on low-quality evidence) showed that differences between SEQ and STT were greater in Europe (RD 0.16, 95% CI 0.14 to 0.19) when compared to Asia, Africa or South America. European studies also showed a tendency towards better efficacy with SEQ; however, this tendency was reversed in 33% of the Asian studies. Africa reported the closest risk difference (RD 0.14 , 95% 0.07 to 0.22) to Europe among studied regions, but confidence intervals were wider and therefore the quality of the evidence showing SEQ to be superior to STT was reduced for this region.Based on high-quality evidence, subgroup analyses showed that SEQ and STT therapies were equivalent when STT lasted for 14 days. Although, overall, the mean eradication proportion with SEQ was over 80%, we noted a tendency towards a lower average effect with this regimen in the more recent studies (2008 and after); weighted linear regression showed that the efficacies of both regimens evolved differently over the years, having a higher reduction in the efficacy of SEQ (-1.72% yearly) than in STT (-0.9% yearly). In these more recent studies (2008 and after) we were also unable to detect the superiority of SEQ over STT when STT was given for 10 days.Based on very low-quality evidence, subgroup analyses on antibiotic resistance showed that the widest difference in efficacy between SEQ and STT was in the subgroup analysis based on clarithromycin-resistant participants, in which SEQ reached a 75% average efficacy versus 43% with STT.Reporting on adverse events (AEs) (RD 0.00, 95% CI -0.02 to 0.02; participants = 8103; studies = 27; I² = 26%, based on high-quality evidence) showed no significant differences between SEQ and STT (20.4% vs 19.5%, respectively) and results were homogeneous.The quality of the studies was limited due to a lack of systematic reporting of the factors affecting risk of bias. Although randomisation was reported, its methodology (e.g. algorithms, number of blocks) was not specified in several studies. Additionally, the other 'Risk of bias' domains (such as allocation concealment of the sequence randomisation, or blinding during either performance or outcome assessment) were also unreported.However, subgroup analyses as well as sensitivity analyses or funnel plots indicated that treatment outcomes were not influenced by the quality of the included studies. On the other hand, we rated 'length of STT' and AEs for the main outcome as high-quality according to GRADE classification; but we downgraded 'publication date' quality to moderate, and 'geographic region' and 'antibiotic resistance' to low- and very low-quality, respectively. AUTHORS' CONCLUSIONS: Our meta-analysis indicates that prior to 2008 SEQ was more effective than STT, especially when STT was given for only seven days. Nevertheless, the apparent advantage of sequential treatment has decreased over time, and more recent studies do not show SEQ to have a higher efficacy versus STT when STT is given for 10 days.Based on the results of this meta-analysis, although SEQ offers an advantage when compared with STT, it cannot be presented as a valid alternative, given that neither SEQ nor STT regimens achieved optimal efficacy ( ≥ 90% eradication rate).

Optimum duration of regimens for Helicobacter pylori eradication.

BACKGROUND: The optimal duration for Helicobacter pylori (H. pylori) eradication therapy is controversial, with recommendations ranging from 7 to 14 days. Several systematic reviews have attempted to address this issue but have given conflicting results and limited their analysis to proton pump inhibitor (PPI), two antibiotics (PPI triple) therapy. We performed a systematic review and meta-analysis to investigate the optimal duration of multiple H. pylori eradication regimens. OBJECTIVES: The primary objective was to assess the relative effectiveness of different durations (7, 10 or 14 days) of a variety of regimens for eradicating H. pylori. The primary outcome was H. pylori persistence. The secondary outcome was adverse events. SEARCH METHODS: The Cochrane Library, MEDLINE, EMBASE, and CINAHL were searched up to December 2011 to identify eligible randomised controlled trials (RCTs). We also searched the proceedings of six conferences from 1995 to 2011, dissertations and theses, and grey literature. There were no language restrictions applied to any search. SELECTION CRITERIA: Only parallel group RCTs assessing the efficacy of one to two weeks duration of first line H. pylori eradication regimens in adults were eligible. Within each regimen, the same combinations of drugs at the same dose were compared over different durations. Studies with at least two arms comparing 7, 10, or 14 days were eligible. Enrolled participants needed to be diagnosed with at least one positive test for H. pylori on the basis of a rapid urease test (RUT), histology, culture, urea breath test (UBT), or a stool antigen test (HpSA) before treatment. Eligible trials needed to confirm eradication of H. pylori as their primary outcome at least 28 days after completion of eradication treatment. Trials using only serology or a polymerase chain reaction (PCR) to determine H. pylori infection or eradication were excluded. DATA COLLECTION AND ANALYSIS: Study eligibility and data extraction were performed by two independent review authors. Data analyses were performed within each type of intervention, for both primary and secondary outcomes. The relative risk (RR) and number needed to treat (NNT)/number needed to harm (NNTH) according to duration of therapy were calculated using the outcomes of H. pylori persistence and adverse events. A random-effects model was used. Subgroup analyses and sensitivity analyses were planned a priori. MAIN RESULTS: In total, 75 studies met the inclusion criteria. Eight types of regimens were reported with at least two comparative eligible durations. They included: PPI + two antibiotics triple therapy (n = 59), PPI bismuth-based quadruple therapy (n = 6), PPI + three antibiotics quadruple therapy (n = 1), PPI dual therapy (n = 2), histamine H2-receptor antagonist (H2RA) bismuth quadruple therapy (n = 3), H2RA bismuth-based triple therapy (n = 2), H2RA + two antibiotics triple therapy (n = 3), and bismuth + two antibiotics triple therapy (n = 2). Some studies provided data for more than one regimen or more than two durations.For the PPI triple therapy, 59 studies with five regimens were reported: PPI + clarithromycin + amoxicillin (PCA); PPI + clarithromycin + a nitroimidazole (PCN); PPI + amoxicillin + nitroimidazole (PAN); PPI + amoxicillin + a quinolone (PAQ); and PPI + amoxicillin + a nitrofuran (PANi). Regardless of type and dose of antibiotics, increased duration of PPI triple therapy from 7 to 14 days significantly increased the H. pylori eradication rate (45 studies, 72.9% versus 81.9%), the RR for H. pylori persistence was 0.66 (95% CI 0.60 to 0.74), NNT was 11 (95% CI 9 to 14). Significant effects were seen in the subgroup of PCA (34 studies, RR 0.65, 95% CI 0.57 to 0.75; NNT 12, 95% CI 9 to 16); PAN (10 studies, RR 0.67, 95% CI 0.52 to 0.86; NNT = 11, 95% CI 8 to 25); and in PAQ (2 studies, RR 0.37, 95% CI 0.16 to 0.83; NNT 3, 95% CI 2 to 10); but not in PCN triple therapy (4 studies, RR 0.87, 95% CI 0.71 to 1.07). Significantly increased eradication rates were also seen for PPI triple therapy with 10 versus 7 days (24 studies, 79.9% versus 75.7%; RR 0.80, 95% CI 0.72 to 0.89; NNT 21, 95% CI 15 to 38) and 14 versus 10 days (12 studies, 84.4% versus 78.5%; RR 0.72, 95% CI 0.58 to 0.90; NNT 17, 95% CI 11 to 46); especially in the subgroup of PAC for 10 versus 7 days (17 studies, RR 0.80, 95% CI 0.70 to 0.91) and for 14 versus 10 days (10 studies, RR 0.69, 95% CI 0.52 to 0.91). A trend towards increased H. pylori eradication rates was seen with increased duration of PCN for 10 versus 7 days, and of PAN for 10 versus 7 days and 14 versus 10 days, though this was not statistical significant. The proportion of patients with adverse events, defined by authors, was marginally significantly increased only between 7 days and 14 days (15.5% versus 19.4%; RR 1.21, 95% CI 1.06 to 1.37; NNTH 31, 95% CI 18 to 104) but not for other duration comparisons. The proportion of patients discontinuing treatment due to adverse events was not significantly different between treatment durations.Only limited data were reported for different durations of regimens other than PPI triple therapy. No significant difference of the eradication rate was seen for all regimens according to different durations except for H2RA bismuth quadruple therapy, where a significantly higher eradication rate was seen for 14 days versus 7 days, however only one study reported outcome data. AUTHORS' CONCLUSIONS: Increasing the duration of PPI-based triple therapy increases H. pylori eradication rates. For PCA, prolonging treatment duration from 7 to 10 or from 10 to 14 days is associated with a significantly higher eradication rate. The optimal duration of therapy for PCA and PAN is at least 14 days. More data are needed to confirm if there is any benefit of increasing the duration of therapy for PCN therapy. Information is limited for regimens other than PPI triple therapy; more studies are needed to draw meaningful conclusions for optimal duration of other H. pylori eradication regimens.

Use of deamidated gliadin peptide antibodies to monitor diet compliance in childhood celiac disease.

OBJECTIVE: The aim of this study was to evaluate performance of serum antibodies against deamidated gliadin peptides (a-DGPs) in detecting compliance with gluten-free diet (GFD) in children with celiac disease (CD). PATIENTS AND METHODS: Serum samples were collected the same day of endoscopy in 95 children with CD and 106 controls. We preliminarily calculated the cutoff of a-DGP immunoglobulin A (IgA) and a-DGP IgA+G in our population by receiver operating characteristic (ROC) curves. Of 95 children with CD, 28 were studied during the first year after GFD introduction, with interview and serum collection every 3 months. In addition, serum samples were collected in 106 children with CD on GFD for more than 1 year (range 1-14). In both groups of children with CD on GFD, we compared a-DGP IgA and IgA+G performance in monitoring compliance with GFD with anti-tissue transglutaminase antibodies (anti-tTG) IgA and anti-gliadin antibody (AGA) IgA. RESULTS: The cutoff resulted in 13.1 arbitrary units (AU) for a-DGP IgA (sensitivity 87.4, 95% confidence interval [CI] 79%-92%, specificity 97.2, 95% CI 92%-99%) and 16.5 for a-DGP IgA+G (sensitivity 94.7, 95% CI 88%-98%, specificity 89.6, 95% CI 84%-95%). In the first year of GFD, at 6 to 8 months prevalence of positive a-DGPs was significantly higher in partially versus strictly compliant children, and at 9 to 12 months only prevalence of positive a-DGP IgA+G remained significantly higher. Moreover, at 9 to 12 months sensitivity to detect transgressions to GFD was 44% for a-DGP IgA and 100% for a-DGP IgA+G (P = 0.03). In the 106 children on GFD for more than 1 year, sensitivity to detect transgressions to GFD was 60% for a-DGP IgA and 76% for a-DGP IgA+G. Anti-tTG IgA and AGA IgA sensitivity was much lower (24% and 4%, respectively). The 4 tests showed comparable high specificity. CONCLUSIONS: Both a-DGPs showed higher sensitivity than anti-tTG IgA and AGA IgA in monitoring compliance with GFD, but a-DGP IgA+G seemed to perform better. a-DGPs did not outperform anti-tTG IgA for CD screening.

Sequential therapy versus tailored triple therapies for Helicobacter pylori infection in children.

AIMS: The aim of the study was to compare sequential versus tailored triple therapy regimens on Helicobacter pylori (H pylori) eradication rates in children and to assess the effect of antimicrobial susceptibility. PATIENTS AND METHODS: Prospective, open-label, multicenter study. Children received randomly either a 10-day sequential treatment comprising omeprazole (OME) with amoxicillin for 5 days and OME, clarithromycin (CLA), and metronidazole (MET) for the remaining 5 days, or a 7-day triple therapy comprising OME with amoxicillin and CLA in cases of a CLA-susceptible strain or MET in cases of CLA-resistant strain. H pylori eradication was assessed by C-urea breath test. RESULTS: One hundred sixty-five children, 95 girls and 70 boys, of median age 10.4 years, were included. The intention-to-treat (ITT) eradication rate was 76.9% (sequential 68/83 = 81.9%, triple therapy 59/82 = 71.9%, ns), and the per-protocol (PP) eradication rate was 84.6% (sequential 68/77 = 88.3%, triple therapy 59/73 = 81.8%, ns). Eradication rates tended to be higher using the sequential treatment, but the difference was only statistically significant for ITT analysis in children harboring both CLA- and MET-susceptible strains (87.8% vs 68.5%, odds ratio [OR] 3.3, P = 0.03). Both ITT and PP eradication rates were significantly lower with sequential treatment in CLA-resistant compared with CLA-susceptible strains (ITT: 56.2% vs 72.7%, OR 5.5, P = 0.008; PP 64.3% vs 80.0%, OR 7.9, P = 0.009). Both treatments were well tolerated. CONCLUSIONS: Sequential treatment is greatly effective for eradicating H pylori in children except in CLA-resistant strains. Sequential treatment can be used as a first-line therapy, but only in areas with a low CLA resistance rate.

Evidence-based guidelines from ESPGHAN and NASPGHAN for Helicobacter pylori infection in children.

OBJECTIVE: As the clinical implications of Helicobacter pylori infection in children and adolescents continue to evolve, ESPGHAN and NASPGHAN jointly renewed clinical guidelines using a standardized evidence-based approach to develop updated recommendations for children and adolescents in North America and Europe. METHODS: An international panel of 11 pediatric gastroenterologists, 2 epidemiologists, 1 microbiologist, and 1 pathologist was selected by societies that developed evidence-based guidelines based on the Delphi process with anonymous voting in a final face-to-face meeting. A systematic literature search was performed on 8 databases of relevance including publications from January 2000 to December 2009. After excluding nonrelevant publications, tables of evidence were constructed for different focus areas according to the Oxford classification. Statements and recommendations were formulated in the following areas: whom to test, how to test, whom to treat, and how to treat. Grades of evidence were assigned to each recommendation based on the GRADE system. RESULTS: A total of 2290 publications were identified, from which 738 were finally reviewed. A total of 21 recommendations were generated, and an algorithm was proposed by the joint committee providing evidence-based guidelines on the diagnostic workup and treatment of children with H pylori infection. CONCLUSIONS: These clinical practice guidelines represent updated, best-available evidence and are meant for children and adolescents living in Europe and North America, but they may not apply to those living on other continents, particularly in developing countries with a high H pylori infection rate and limited health care resources.

Clarithromycin resistance of Helicobacter pylori strains isolated from children' gastric antrum and fundus as assessed by fluorescent in-situ hybridization and culture on four-sector agar plates.

AIM: To assess validity of culture on four-sector agar plates and fluorescent in-situ hybridization (FISH) test, and clarithromycin resistance rate in Helicobacter pylori strains isolated from children in the last 10 years. METHODS: In the last 5 years, gastric biopsy specimens from antrum and fundus were taken from 89 consecutive children (median age 9 years) with H. pylori gastritis and from 21 controls. Culture was performed on 176 gastric biopsies (89 from antrum, 87 from fundus) on four-sector agar plates, and FISH test with DNA ProbeMix. After its validity was evaluated, FISH test was applied on additional 119 biopsies from 68 children (68 from the antrum, 51 from the fundus) stored in the Pathology archive in the previous 5 years. RESULTS: Culture was positive in 157 of 176 biopsies (sensitivity: 89.2%, 95% confidence interval (CI) 85-94). In 33 of 89 children (37%) resistant strains were found in one or both gastric sites. FISH test was positive in 148 of 176 biopsies from infected children (sensitivity 84.1%, 95%CI 79-89) and in none of 42 biopsies from controls (specificity 100%). When applied on archive biopsies, FISH test was positive in 96 of 119 (80.7%, 95%CI 74-88). Total children harboring resistant strains in the last 10 years, as assessed by FISH test, were 66 of 157 (42%). Mixed infection with both sensitive and resistant strains were found in 40 children (25%) and in 12 of them resistant strains were in the fundus only. CONCLUSIONS: Culture on four-sector agar plates and FISH test had a high sensitivity and specificity and showed co-presence of sensitive and resistant strains. In one-third of children with mixed infection, the resistant strains were in the fundus only. Clarithromycin resistance should be assessed in biopsies both from the antrum and the fundus, utilizing antral biopsies only can underestimate its prevalence.

Increased interleukin-10 in Helicobacter pylori infection could be involved in the mechanism protecting from allergy.

BACKGROUND: A protective effect of Helicobacter pylori infection against allergic diseases has been reported. The increasing incidence of childhood allergy in developed countries may be a result of reduced stimulation of the immune system by early chronic infections, with the protective effect of gastrointestinal microbes being mediated by regulatory T lymphocytes and production of interleukin (IL)-10. To elucidate a possible mechanism involved in protecting against the development of atopy, we measured expression of IL-10 in gastric mucosa of children with H pylori gastritis. PATIENTS AND METHODS: Gastric biopsies were performed during endoscopy in 48 children (median age, 9 years), 32 of whom had H pylori gastritis and 16 of whom served as controls. Interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), and IL-10 were measured in tissue homogenate by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The amounts of IFN-gamma, IL-1beta, and IL-10 transcripts were quantified via competitive RT-PCR with use of dilution series of specific competitors. RESULTS: Expression of IFN-gamma and IL-10 were significantly higher in H pylori-infected children. No direct correlation with age was found, but a further increase in IL-10 expression was found in H pylori-infected children older than 4 years, whereas in control subjects, IL-10 expression tended to be lower in older children. IL-1beta expression was similar in infected children and control subjects. In H pylori-infected children, the prevalence of allergy was significantly higher in children with lower cytokine expression in gastric mucosa. CONCLUSIONS: In children, H pylori-induced inflammatory response is associated with development of cell-mediated immunity of T-helper 1 type, as demonstrated by increased IFN-gamma expression. The significantly increased expression of gastric IL-10 in H pylori-infected children and its further increase in older children suggest that this chronic infection may influence IL-10 production even beyond the age of 4 years. H pylori may be one of the infections with the potential to modulate immune responses.

Clinical pattern of celiac disease is still changing.

The clinical presentation of celiac disease in children changed in the last decades of the 20th century. To ascertain whether changes are still in progress, we analyzed symptoms at presentation and age at diagnosis in 307 children receiving diagnoses of celiac disease for the past 20 years. The prevalence of typical forms of celiac disease decreased in the past decade, particularly in the past 5 years (from 76% in 1987-1990 to 44%, P < 0.0001). Age at diagnosis (5.9 y, P = 0.01) and silent forms (10.6%, P = 0.003) have significantly increased in the past 5 years. Histological examination showed decreased subtotal and increased partial villous atrophy prevalence (P = 0.02).

In vivo expression of the 25-kDa laminin-binding protein of Helicobacter pylori.

The gastroduodenal pathogen Helicobacter pylori has been shown to inhibit the interaction between the extracellular matrix protein laminin and its receptor on gastric epithelial cells, potentially contributing to a loss of mucosal integrity. As a 25-kDa outer membrane protein of H. pylori in association with the bacterial lipopolysaccharides (LPS) mediates attachment to laminin, the aim of this study was to determine whether the 25-kDa protein is produced by H. pylori in infected hosts. We examined the immune response to the 25-kDa laminin binding protein in 12 paediatric patients; samples from a H. pylori-negative healthy adult were used as controls. In immunoblotting, antibodies to a 25-kDa protein were found in the serum and saliva of H. pylori-positive individuals only, and using the positive sera and saliva, laminin binding to the 25-kDa protein was inhibited. Thus, the 25-kDa laminin-binding protein is produced by H. pylori in infected hosts.

Histological score for cells with irregular nuclear contours for the diagnosis of reflux esophagitis in children.

Histological criteria for the diagnosis of reflux esophagitis include basal zone hyperplasia, stromal papillae elongation, and inflammatory infiltrate. However, endoscopic esophageal biopsy specimens may include little or no lamina propria. Intraepithelial T lymphocytes, seen in hematoxylin and eosin-stained sections as cells with irregular nuclear contours (CINC), may have a higher density in children with esophagitis. We evaluated the diagnostic accuracy of a numerical score built up by grading the "classical" parameters and its correlation with CINC density in grasp biopsy specimens obtained from children undergoing esophagogastroduodenoscopy with and without esophagitis. We analyzed esophageal biopsy specimens from 349 children (median age, 5 years) subdivided in 4 groups according to the previous routine histology report: group 1, 144 children with esophagitis; group 2, 65 controls; group 3, 51 children with dubious esophagitis; and group 4, 75 children with esophagitis on endoscopy but a normal histology report. A numerical value was assigned to each parameter; the sum of these values represented the histological score. We also evaluated intraepithelial CINC density (ie, number of CINC per high-power field). We separately analyzed histological sections with and without lamina propria. For both total score and for CINC density, we calculated a cutoff using a receiver operating characteristic curve. Cutoffs of 6 for score and of 4 for CINC density provided the best sensitivity and specificity. Sensitivity of the histological score was better in biopsy specimens containing lamina propria (94%) than in those without lamina propria (4%). Sensitivity of CINC density was satisfactory in both specimens with (78%) and without (75%) lamina propria. Specificity was satisfactory for both parameters. In conclusion, when lamina propria was present in sections of endoscopic esophageal biopsy specimens, histological score provided a better diagnostic accuracy for the diagnosis of esophagitis. However, when no lamina propria was present, as was the case in 67% of our children, CINC density had better sensitivity. In addition, this latter parameter showed esophageal mucosa damage in 34% of previously dubious cases or cases with esophagitis at endoscopy but a previous routine histology report of normal mucosa.

Eosinophilic oesophagitis in children: responders and non-responders to swallowed fluticasone.

UNLABELLED: Eosinophilic Oesophagitis (EO) is characterised by large numbers of eosinophils in oesophageal mucosa in response to food or inhaled antigens. Treatment with elimination diet or corticosteroids lead to improvement in some children, but their efficacy is not optimal. AIM: of this study is to identify clinical, endoscopic and/or histological features associated with response to treatment with swallowed fluticasone propionate. PATIENTS AND METHODS: In the last 12 years 34 children (M/F 25/9) with EO were treated with fluticasone propionate spray 250 µg/puff by inhaler without spacer, three puffs three times a day for 6 weeks, and returned for a follow-up endoscopy. At histology 25 of them were found to be responders to therapy (73.5%) and 9 were non-responders. Anthropometric characteristics, symptoms at presentation, endoscopic and histological data at baseline between responders and non-responders were compared. RESULTS: Age, sex, height, duration and type of main symptom at presentation, type of allergy and number of allergens, peripheral eosinophil counts an serum IgE were similar in responders and non-responders. At baseline histology findings responders had a more severe inflammation: median peak eosinophils/high power field was higher (76 vs 44 in non responders p=0.04), eosinophilic microabscesses were present in a significantly higher number of responders (p=0.04) and peak mast cells/ high power field was significantly higher (p=0.001). CONCLUSIONS: Clinical characteristics of children with EO at baseline were similar in responders and non-responders, but a more severe inflammation in oesophageal mucosa was associated with a higher response rate to fluticasone treatment.

Helicobacter pylori Infection in European children with gastro-duodenal ulcers and erosions.

BACKGROUND: To analyze risk factors associated with gastro-duodenal ulcers and erosions in children. METHODS: Open, prospective, multicenter, case-control study carried out in 11 European countries in patients with gastric or duodenal ulcers/erosions and 2 age-matched controls each. Possible risk factors were recorded. Logistic regression models were performed with adjustment for centers and age groups. RESULTS: Seven-hundred thirty-two patients (244 cases, 153 with erosions only and 91 with ulcers, and 488 controls) were recruited. Children receiving antimicrobials or acid suppressive drugs before endoscopy were excluded (202 cases/390 controls remained for risk factor analysis). Helicobacter pylori was detected more frequently in cases than controls but only in 32.0% versus 20.1% in controls (P = 0.001). Independent exposure factors for gastric ulcers were male gender (P = 0.001), chronic neurologic disease (P = 0.015), chronic renal disease (P < 0.001) and nonsteroidal anti-inflammatory drug consumption (P = 0.035). Exposure factors for duodenal ulcers were H. pylori infection (P < 0.001) and steroid consumption (P = 0.031). Chronic renal disease was the only independent factor associated with gastric erosions (P = 0.026), those associated with duodenal erosions being H. pylori infection (P = 0.023), active smoking (P = 0.006) and chronic arthritis (P = 0.008). No risk factor was identified in 97/202 (48.0%) cases. CONCLUSIONS: H. pylori remains a risk factor for duodenal, but not for gastric lesions in children in countries with low prevalence of infection. No risk factor could be identified in half of the children with gastro-duodenal ulcers/erosions.

Delayed-release oral suspension of omeprazole for the treatment of erosive esophagitis and gastroesophageal reflux disease in pediatric patients: a review.

Omeprazole is a proton-pump inhibitor indicated for gastroesophageal reflux disease and erosive esophagitis treatment in children. The aim of this review was to evaluate the efficacy of delayed-release oral suspension of omeprazole in childhood esophagitis, in terms of symptom relief, reduction in reflux index and/or intragastric acidity, and endoscopic and/or histological healing. We systematically searched PubMed, Cochrane and EMBASE (1990 to 2009) and identified 59 potentially relevant articles, but only 12 articles were suitable to be included in our analysis. All the studies evaluated symptom relief and reported a median relief rate of 80.4% (range 35%-100%). Five studies reported a significant reduction of the esophageal reflux index within normal limits (<7%) in all children, and 4 studies a significant reduction of intra-gastric acidity. The endoscopic healing rate, reported by 9 studies, was 84% after 8-week treatment and 95% after 12-week treatment, the latter being significantly higher than the histological healing rate (49%). In conclusion, omeprazole given at a dose ranging from 0.3 to 3.5 mg/kg once daily (median 1 mg/kg once daily) for at least 12 weeks is highly effective in childhood esophagitis.

Frequency and risk factors of gastric and duodenal ulcers or erosions in children: a prospective 1-month European multicenter study.

UNLABELLED: There are no solid figures of the frequency of ulcer disease during childhood in Europe. We assessed its frequency and analyzed known risk factors. PATIENTS AND METHODS: Ulcers, erosions, indications, and risk factors were recorded in all children undergoing an upper gastrointestinal endoscopy in a prospective study carried out during 1-month simultaneously in 19 centers among 14 European countries. RESULTS: Ulcers and/or erosions were observed in 56 out of 694 children. Children with ulcers/erosions were significantly older than those without lesions (10.3+/-5.5 vs. 8.1+/-5.7 years, P=0.002). Helicobacter pylori infection was present in 15 of 56 children (27%) where NSAIDs were used in eight, steroids in five, immune-suppressive drugs in five, antibiotics in six, antacids in one, H2-blockers in six and proton pump inhibitors in eight children (more than one risk factor was detected in 32 of 56 children). No risk factors were observed in 24 of 56 children (43%). The main indications for endoscopy were epigastric or abdominal pain (24%) and suspicion of gastroesophageal reflux disease (15%). Similarly, epigastric tenderness, hematemesis, melena, and weight stagnation were significantly associated with ulcers/erosions, whereas sex, H. pylori infection, socioeconomic and lifestyle factors were equally distributed. CONCLUSION: Although limited by the short-time duration and the heterogeneity of the patients included throughout the 19 centers, our study shows a frequency of 8.1% of ulcers and/or erosions in children, occurring mainly in the second decade of life. H. pylori infection and gastrotoxic medications were less frequently implicated than expected.

Results from the pediatric European register for treatment of Helicobacter pylori (PERTH).

BACKGROUND AND AIM: Data on the eradication treatment for childhood Helicobacter pylori are scanty. A register was established on the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) website to collect data on treatment performed by European pediatricians to ascertain what is practiced in the field. SUBJECTS: From January 2001 to December 2002, information on 597 children were entered by 23 European Centers, but only data of 518 treated children were completed and analyzed (86.7%, 262 male subjects, median age 9 years, range 1-14). According to their nationality, 226 children were from Southern Europe, 132 from Eastern Europe, 68 from Western Europe, and 4 from northern Europe, 68 from North Africa, and 20 from Asia. At endoscopy, 454 children had gastritis and 64 had ulcer (12.3%). Antibiotic sensitivity, tested in 361 cases, revealed 18% clarithromycin-resistant and 19% metronidazole-resistant H. pylori strains. RESULTS: Treatment was performed for 1 week in 388 and for 2 weeks in 130 children. Antibiotics were associated with proton pump inhibitors (PPI) in 345 and with bismuth in 121 children. Triple therapy was given to 485 children, dual therapy to 26, quadruple to 7. Follow-up data, by (13)C-Urea-Breath Test or histology or both, were available for 480 children. Overall eradication rate was 65.6%, significantly higher in children with ulcer (79.7%) than without (63.9%, p = .001). When given as first treatment, bismuth-containing triple therapies were more efficacious than PPI-containing ones (77% versus 64%, p = .02, OR 1.88, 95% CI 1.1-3.3). Twenty-seven different treatment regimens were used, but only six were administered to at least 18 children (range 18-157). There was no difference between treatments given for 1 or 2 weeks, or given as first or second therapies. CONCLUSION: European pediatricians entering data in the register used 27 different regimens. Bismuth-containing therapies resulted in higher eradication rate. Omeprazole-containing triple therapies were the most used although their efficacy was low. Therapies recommended for adults do not appear to be suitable for children.

High accuracy of noninvasive tests to diagnose Helicobacter pylori infection in very young children.

OBJECTIVE: To validate the (13)C-urea-breath-test (UBT) and stool antigen test (HpSA) in children aged 5 years or younger, against invasive histologic study and rapid-urease-testing or culture. STUDY DESIGN: On all consecutive children aged 5 years or younger undergoing endoscopy in 1 single center during the last 7.5 years, UBT and HpSA were performed. RESULTS: Of a total of 184 children (median age 2.2 years, range 0.2-5.5), 30 were Helicobacter pylori-positive (16.3%). Sensitivity and specificity of UBT were 93.3% (95%CI 77.9%-99.2%) and 95.5% (90.9-98.2), with a cutoff of 5 per thousand, but specificity increased to 98.1% (94.4%-99.6%) with a cutoff of 8 per thousand. Sensitivity and specificity of HpSA were 93.3% (77.9%-99.2%) and 98.7% (95.4%-99.8%). CONCLUSION: Accuracy of noninvasive tests in our single-center study were satisfactory: specificity of UBT improved with a cutoff at 8%, and sensitivity of HpSA was high when determined locally without transportation after long or inadequate storage that could impair results.

Mechanisms of abnormal puberty in coeliac disease.

Coeliac disease (CD) is one of the most frequent chronic diseases in childhood. The clinical spectrum has changed; in addition to the classical gastrointestinal form, other clinical manifestations have been described, such as hypogonadism and the consequent delay in onset of puberty. Recent studies reported not only a significantly retarded menarche in untreated CD girls as compared with girls following a gluten-free diet, but also in treated CD a negative effect on pregnancy, resulting in lower birth weight and shorter duration of pregnancy. In boys, there is a reduced serum level of dihydrotestosterone and an increased serum level of luteinizing hormone, an abnormality pattern suggesting androgen resistance. The pathogenesis of CD-related reproductive disorders is still unclear. Some hypotheses may be tried; for example, in CD there is a high level of autoantibodies directed against self-antigens, so there could be antibodies directed against hormones or organs critical for pubertal development. Moreover, in CD there could be a selective malabsorption of micronutrients essential for the metabolism of carrier or receptor proteins for sex hormones.