Luiz Edmundo Mazzoleni

Helicobacter pylori eradication in functional dyspepsia: HEROES trial.

BACKGROUND Eradication of Helicobacter pylori in patients with functional dyspepsia continues to be a matter of debate. We studied eradication effects on symptoms and quality of life of primary care patients. METHODS Helicobacter pylori -positive adult patients with functional dyspepsia meeting the Rome III International Consensus criteria were randomly assigned to receive omeprazole, amoxicillin trihydrate, and clarithromycin, or omeprazole plus placebo for 10 days. Endoscopy and H pylori tests were performed at screening and at 12 months. Outcome measures were at least 50% symptomatic improvement at 12 months using a validated disease-specific questionnaire (primary end point), patient global assessment of symptoms, and quality of life. RESULTS We randomly assigned 404 patients (78.7% were women; mean age, 46.1 years); 201 were assigned to be treated with antibiotics (antibiotics group) and 203 to a control group. A total of 389 patients (96.3%) completed the study. The proportion of patients who achieved the primary outcome was 49.0% (94 of 192) in the antibiotics group and 36.5% (72 of 197) in the control group (P = .01; number needed to treat, 8). In the patient global assessment of symptoms, 78.1% in the antibiotics group (157 of 201) answered that they were better symptomatically, and 67.5% in the control group (137 of 203) said that they were better (P = .02). The antibiotics group had a significantly larger increase in their mean (SD) Medical Outcomes Study 36-Item Short Form Health Survey physical component summary scores than the control group did (4.15 [8.5] vs 2.2 [8.1]; P = .02). CONCLUSION Helicobacter pylori eradication provided significant benefits to primary care patients with functional dyspepsia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00404534.

Clinical outcomes of eradication of Helicobacter pylori in nonulcer dyspepsia in a population with a high prevalence of infection : results of a 12-month randomized, double blind, placebo-controlled study

Ninety-one Helicobacter pylori-positive patients with nonulcer dyspepsia were randomized to receive either lansoprazole, amoxicillin, and clarithromycin or lansoprazole and placebo. A validated questionnaire assessed dyspeptic symptoms at baseline and at 3, 6, and 12 months. Endoscopies and biopsies were performed at baseline and at 3 and 12 months. There was an overall trend, although not statistically significant, for a benefit of H. pylori eradication. Of the patients in the antibiotics group, 16 of 46 (35%) had symptomatic improvement, versus 9 of 43 (21%) in the control group (P = 0.164). In a secondary analysis, it was found that of the patients without endoscopic gastric erosions, 15 of 34 (44%) in the antibiotics group and 5 of 33 (15%) of controls had symptomatic improvement (P = 0.015). Helicobacter pylori eradication did not prove to be clinically beneficial, although a tendency to symptomatic benefit was detected. Further studies are necessary to confirm the implications of endoscopic gastric erosions in these patients.

Development and validation of a cross-cultural questionnaire to evaluate nonulcer dyspepsia: the Porto Alegre Dyspeptic Symptoms Questionnaire (PADYQ).

Despite its high prevalence, nonulcer dyspepsia is still difficult to study, due to the lack of adequate tools to measure significant outcomes. The objective of this study was to develop and validate a symptom-focused, disease-specific questionnaire to evaluate patients with nonulcer dyspepsia. For that, the questionnaire was carefully written following widely accepted terminology, so as to facilitate translation and validation in other languages and cultures. The questionnaire was developed using Rome I terminology for symptoms, which were evaluated according to their intensity, duration, and frequency when applicable. Thirty-one patients with nonulcer dyspepsia, as well as 31 sex-and age-matched volunteers without digestive problems were used to assess the internal consistency, reproducibility, responsiveness, content validity, and discriminant validity of the questionnaire. Another 31 functional dyspeptic patients were enrolled for assessment of criterion validity. Cronbach’s α coefficient was 0.82. The intraclass correlation coefficient for the scores obtained 7 days apart was 0.86. The mean score obtained after 3 months of treatment was 16.4, vs. 23.03 at baseline (P=0.001). Two blinded gastroenterologists agreed that the questionnaire adequately evaluated nonulcer dyspepsia. The median symptoms score for controls was 0, vs. 22.5 for dyspeptic patients (P=0.001). An inverse correlation was observed between quality of life and dyspeptic symptoms (R = −0.28, P = 0.026). The proposed questionnaire has high degrees of both reproducibility and responsiveness. As this questionnaire was based on Rome I International Consensus terminology, it is expected that it will be easy to translate and validate.

Helicobacter pylori eradication does not cause reflux oesophagitis in functional dyspeptic patients: a randomized, investigator-blinded, placebo-controlled trial

Background : The protective role of Helicobacter pylori in gastro‐oesophageal reflux disease has been widely discussed.

Influence of Organic and Functional Dyspepsia on Work Productivity: The HEROES-DIP Study

OBJECTIVES Dyspepsia is defined as persistent or recurrent abdominal pain or discomfort centered in the upper abdomen. Dyspepsia represents up to 8.3% of all primary care physician visits and causes huge economic costs to patients and to the economy as a whole. The aim of this study was to measure the influence of dyspepsia on work productivity of people within the Brazilian workforce. METHODS Adult patients were enrolled if they met the Roma III criteria for uninvestigated dyspepsia. All patients answered a demographic questionnaire. Productivity impairment was measured by the Work Productivity and Activity Impairment questionnaire. Subjects underwent upper gastrointestinal endoscopy and were classified as having functional or organic dyspepsia. The study protocol was approved by the Ethics Committee of Hospital de Clínicas de Porto Alegre, Brazil. RESULTS Eight hundred fifty patients with dyspepsia were evaluated: 628 were women (73.9%); mean age was 46.4 ± 12.9 years; 387 (45.5%) were active workers. Among active workers, 32.2% mentioned that dyspepsia had caused absenteeism from work during the preceding week and 78% reported a reduction of the work productivity (presenteeism). The lost work productivity score was 35.7% among all employed patients. The affect on work productivity was similar between patients with functional or organic dyspepsia. CONCLUSIONS Our study showed an important influence of dyspepsia on work productivity. We did not find any statistically significant difference on the influence on work between patients with organic dyspepsia and functional dyspepsia. The social impact of these findings is underscored by taking into account the prevalence (up to 40%) of this condition in Brazil.

Mass eradication of Helicobacter pylori: feasible and advisable?

In The Lancet, E Robert Greenberg and colleagues present an Article about the effi cacy of three diff erent therapeutic regimens for the eradication of Helicobacter pylori in several Latin American countries. A large sample of adults with symptomatic and asymptomatic disease was studied. Besides aiming to identify the best therapeutic regimen, the study also served as a preliminary step to support future programmes of gastric cancer prevention in the Latin American population. Gastric cancer is the fi fth most common cause of cancer in this region (fi gure) and is the leading cause of cancer mortality among males in many Latin American countries. The study showed that the 14-day standard therapy with lansoprazole, amoxicillin, and clarithromycin was superior to both the 5-day concomitant and sequential four-drug regimens (lansoprazole, amoxicillin, clarithromycin, and metronidazole). Generic (off -patent) preparations of the study drugs were used in this trial. The use of low-cost generic drugs is an important factor for public health strategies in Latin America. These preparations were validated in the USA and the results from the study done by Greenberg and colleagues show that good quality generic drugs were used. However, if these drugs are used in large populations for H pylori eradication, quality control of grafts; choice of biological or genetic markers for subsets of patients most likely to benefi t; assessments of outcome through new validated activity scores; defi nitions of drugfree remission; required durations of follow-up to assess risk of relapse; and defi nition of cure for an autoimmune disease such as systemic sclerosis for which the term cure is not defi ned. Although randomised trials are key, other types of studies are appropriate, and capture of data from all trials including non-randomised studies is important as promoted by the European Group for Blood and Marrow Transplantation (EBMT). Multicentre collaboration is crucial to establish the best therapeutic approach, with analysis of shared registry data and biological material obtained with adequate technical platforms. In this context, the European Orphan Disease Plan, which includes national and regional centres of reference and networks for HSCT in autoimmune diseases, might help to extend the important fi ndings of ASSIST.

S1279 Brazilian Prevalence of Irritable Bowel Syndrome: A Population-Based Study

BACKGROUND: The prevalence of irritable bowel syndrome (IBS) in the developed world is estimated to be 10% to 20%. To our knowledge, there is no studies evaluating the nation wide prevalence of IBS in South America. AIMSM mean age of the sample: 37.6y (SD13.8y). Prevalence of IBS in the entire sample: 24.7 %. Prevalence by sex: males 15.7%, females 30.2%. Logistic regression did show that sex (female), age (younger) and level of education (less education) were associated with higher prevalence of IBS in our population while social class and geographical regions of Brazil had no impact. CONCLUSIONS: This first large population-based survey conducted in South America estimates the prevalence and the sex distribution of IBS in Brazil to be comparable to the observed in the Western developed countries. Our data suggest that the prevalence is higher in females, younger and less educated persons. Regarding IBS sub-types there was a higher prevalence of females with IBS-C, IBS-U and IBS-M. Prevalence of the different IBS subtypes

Influence of CYP2C19 on Helicobacter pylori eradication in Brazilian patients with functional dyspepsia

The aim of this study was to examine the effect of polymorphisms in the cytochrome P450 (CYP) 2C19 gene (CYP2C19) on the Helicobacter pylori eradication rate in Brazilian patients with functional dyspepsia. Adults diagnosed with functional dyspepsia based on the ROME III criteria and infected with H. pylori were recruited to this study. The patients were subjected to gastrointestinal endoscopy and the H. pylori status was defined when both urease test and histopathology results were negative or positive. The patients were treated with proton pump inhibitor-based triple therapy (omeprazole, amoxicillin, and clarithromycin). CYP2C19*2 and CYP2C19*3 were genotyped by polymerase chain reaction-restriction fragment length polymorphism. One hundred and forty-eight patients (81.8% women) with a mean (± SD) age of 46.1 (12.2) years were included in this study. Based on the CYP2C19 genotypes, the patients were classified as homozygous extensive metabolizer (HomEM; 67.6%), heterozygous extensive metabolizer (HetEM; 26.3%), or poor metabolizer (PM; 6.1%). The H. pylori eradication rates in patients with HomEM, HetEM, and PM were 85.0, 89.7, and 100.0% (P = 0.376), respectively. The included study population comprised a high frequency of patients carrying the HomEM genotype. Although the genotypes of CYP2C19 variants were not statistically significant, the results of this study suggest a possible effect of the PM genotype on the efficacy of H. pylori eradication.

Helicobacter pylori eradication: influence of interleukin-1beta –31 C/T polymorphism

AIM To analyze the influence of the -31 C/T polymorphism of the interleukin-1β gene on Helicobacter pylori eradication therapy success in patients with functional dyspepsia. METHODS Functional dyspepsia was diagnosed according to the Rome III criteria. All patients underwent upper gastrointestinal endoscopy, and gastric biopsies were obtained at screening and 12 months after randomization (last follow-up visit). Urease test and histological examination were performed to define the H. pylori status. Patients received twice-daily amoxicillin, clarithromycin and omeprazole for 10 days. Genotyping of the interleukin-1beta -31 C/T polymorphism (rs1143627) was performed using polymerase chain reaction-restriction fragment length polymorphism. RESULTS One hundred forty-nine patients received treatment with triple therapy for H. pylori eradication. Only one patient was lost to follow-up, and adherence to study medication was 94.6%. A total of 148 patients (mean age 46.08 ± 12.24 years; 81.8% women) were evaluated for the influence of the interleukin-1beta -31 C/T polymorphism on the outcome of H. pylori eradication therapy. After treatment, bacteria were eradicated in 87% of patients (129/148). Genotype frequencies of the polymorphism were as follows: CC, 38/148 (25.7%); CT, 71/148 (47.9%); and TT, 39/148 (26.4%). Successful eradication rate was 78.9%, 94.4% and 82.1% for the CC, CT and TT genotypes, respectively. The CT genotype was significantly associated with successful H. pylori eradication (p = 0.039). CONCLUSION This study suggests that the CT genotype of the interleukin-1beta -31 C/T polymorphism plays a role in the successful eradication of H. pylori among patients with functional dyspepsia.

Lack of association between helicobacter pylori's virulence and increased serum C-reactive protein levels in functional dyspeptic patients

BACKGROUND Recently, a great variety of studies aimed to investigate and even suggest Helicobacter pylori as an important key factor in gastrointestinal and non-gastrointestinal events development. The well-established relationship between bacterial virulence and increased risk for peptic ulcer or gastric carcinoma is not so clear when comparing inflammation markers alterations, such C-reactive protein, with the pathogen. OBJECTIVE The objective of this study was to evaluate the presence of H. pylori, bacterial virulence and C-reactive protein serum levels in individuals diagnosed with functional dyspepsia. METHODS Were prospectively included in this study 489 dyspeptic individuals. They fulfill Rome III clinical criteria for the diagnosis of functional dyspepsia with no organic disease at endoscopy. The bacterial infection was established by histology and urease rapid test. The levels of serum C-reactive protein were obtained by immunonefelometry and CagA status of H. pylori positive individuals was determined through an imunoenzimatic assay. RESULTS Prevalence rate of H. pylori was 66.3% and virulence factor CagA was detected in nearly 43% of positive samples. In addition, it has been noticed an association between Ilex paraguariensis (yerba maté) consumption and pathogens prevalence. An important effect of bacterial infection on inflammation was only observed in gastric epithelium. CONCLUSION No systemic response to the pathogen, measured through C-reactive protein levels, was observed, regardless of CagA status. Otherwise, the intake of yerba maté should be considered as a cultural factor possibly related to H. pyloris transmission.