European Registry on Helicobacter pylori management (Hp-EuReg): patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients.

OBJECTIVE: The best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care. DESIGN: International multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables included demographics, previous eradication attempts, prescribed treatment, adverse events and outcomes. Data monitoring was performed to ensure data quality. Time-trend and geographical analyses were performed. RESULTS: 30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empirical H. pylori treatments were included for analysis. Pretreatment resistance rates were 23% to clarithromycin, 32% to metronidazole and 13% to both. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (39%), achieving 81.5% modified intention-to-treat eradication rate. Over 90% eradication was obtained only with 10-day bismuth quadruple or 14-day concomitant treatments. Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates. Time-trend analysis showed a region-dependent shift in prescriptions including abandoning triple therapies, using higher acid-inhibition and longer treatments, which was associated with an overall effectiveness increase (84%-90%). CONCLUSION: Management of H. pylori infection by European gastroenterologists is heterogeneous, suboptimal and discrepant with current recommendations. Only quadruple therapies lasting at least 10 days are able to achieve over 90% eradication rates. European recommendations are being slowly and heterogeneously incorporated into routine clinical practice, which was associated with a corresponding increase in effectiveness.

Helicobacter pylori and Nonmalignant Diseases.

Helicobacter pylori is responsible for most peptic ulcers, plays a role in functional dyspepsia and is thought by some to influence the course of gastroesophageal reflux disease. This article addresses recent studies that have been published in connection with these diseases. H. pylori-associated peptic ulcer is declining in prevalence but the incidence of perforation and bleeding remains high especially in the elderly. All H. pylori associated peptic ulcers should be treated by eradication of the infection. Dyspepsia is a common disorder that affects up to 25% of the population. About 8% of cases that are infected with H. pylori will respond to treatment of the infection. The association between H. pylori and gastroesophageal reflux disease continues to be debated, a number of studies have shown that there is a negative association between H. pylori infection and Gastroesophageal reflux disease but treatment of H. pylori has not been shown to induce reflux or to affect the response to medication. Gastric atrophy is known to extend when acid suppression is used in infected patients implying that H. pylori treatment should be used in infected patients who are to undergo long-term Proton Pump Inhibitor therapy.

Effect of dyspepsia on survival: a longitudinal 10-year follow-up study.

OBJECTIVES: Most chronic and recurrent gastrointestinal (GI) symptoms in the community are caused by functional GI disorders, such as functional dyspepsia and irritable bowel syndrome (IBS). It is not known, however, whether these conditions affect mortality. We present the results of a large community-based prospective study that examines this issue. METHODS: This was a 10-year follow-up, conducted in 2004, of individuals recruited into a community-based screening program for Helicobacter pylori. Data on mortality and cause of death at 10 years were obtained from the Office for National Statistics. Baseline demographic data, lifestyle factors, GI symptoms, and quality of life were recorded at study entry. The effect of all these factors on 10-year mortality was examined using univariate analysis and multivariate Cox regression analysis. All results were expressed as hazard ratios (HRs) with 99% confidence intervals (CIs). RESULTS: Symptom data were available for 8,323 (99.0%) of 8,407 individuals originally enrolled, comprising over 84,000 years of follow-up: 3,169 (38.1%) subjects had dyspepsia, and 264 (3.2%) IBS. There were 137 (1.65%) individuals who had died at 10 years. After multivariate analysis, there was no significant difference in likelihood of death at 10 years in those with dyspepsia (HR: 0.94; 99% CI: 0.58-1.54) or IBS (HR: 1.35; 99% CI: 0.36-5.10), compared with those not meeting the criteria for either condition. CONCLUSIONS: Dyspepsia was not associated with an increased mortality in the community. Data for any effect of IBS on survival were less clear. Further studies are required to assess the impact of functional GI disorders on life expectancy.

Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report.

Management of Helicobacter pylori infection is evolving and in this 4th edition of the Maastricht consensus report aspects related to the clinical role of H pylori were looked at again in 2010. In the 4th Maastricht/Florence Consensus Conference 44 experts from 24 countries took active part and examined key clinical aspects in three subdivided workshops: (1) Indications and contraindications for diagnosis and treatment, focusing on dyspepsia, non-steroidal anti-inflammatory drugs or aspirin use, gastro-oesophageal reflux disease and extraintestinal manifestations of the infection. (2) Diagnostic tests and treatment of infection. (3) Prevention of gastric cancer and other complications. The results of the individual workshops were submitted to a final consensus voting to all participants. Recommendations are provided on the basis of the best current evidence and plausibility to guide doctors involved in the management of this infection associated with various clinical conditions.

Epidemiology of Helicobacter pylori infection and public health implications.

This article summarizes the published literature concerning the epidemiology and public health implications of Helicobacter pylori infection published from April 2009 through March 2010. Prevalence of infection varied between 7 and 87% and was lower in European studies. All retrieved studies examining transmission of infection concluded that spread is from person-to-person. One study collecting stool and vomitus samples from patients with acute gastroenteritis detected H. pylori DNA in 88% of vomitus and 74% of stool samples. Proposed risk factors for infection included male gender, increasing age, shorter height, tobacco use, lower socioeconomic status, obesity, and lower educational status of the parents in studies conducted among children. Decision analysis models suggest preventing acquisition of H. pylori, via vaccination in childhood, could be cost-effective and may reduce incidence of gastric cancer by over 40%. As yet, no country has adopted public health measures to treat infected individuals or prevent infection in populations at risk.

A study of indefinite for dysplasia in Barrett's oesophagus: reproducibility of diagnosis, clinical outcomes and predicting progression with AMACR (alpha-methylacyl-CoA-racemase).

AIMS: To assess interobserver variation in the diagnosis of dysplasia in Barrett's oesophagus, especially indefinite dysplasia (IND) using the revised Vienna classification. A secondary aim was to study clinical outcome of IND cases and to evaluate expression of alpha-methyl-CoA racemase (AMACR) as a marker predictive of progression. METHODS AND RESULTS: Cases of Barrett's oesophagus and dysplasia over a 20 year period were assessed. Three experienced histopathologists reviewed 101 cases on set criteria in a blinded fashion. Slides were immunostained for AMACR and evaluated for the presence, extent and location of AMACR expression. Clinical and progression data were collected. Overall agreement for the diagnosis of dysplasia was fair (k = 0.35) but that for IND was poor (k = 0.18). 6 IND cases progressed after a median follow-up of 31.4 months to a higher grade. The sensitivity of AMACR for the detection of abnormality was 22% for IND and specificity 100%. The positive predictive value of AMACR for progression was 0.44 and the negative predictive value was 0.92. CONCLUSION: Fair agreement was achieved for the diagnosis of dysplasia but poor agreement for IND. A proportion of IND cases progress. Re-diagnosis or consensus diagnosis did not predict progression. AMACR shows promise as a marker to indicate IND patients in need of more intensive surveillance.

Throat spray, sedation or anaesthetic?

Digestive endoscopy covers a wide variety of procedures; the need for sedation is governed by the invasiveness and length of the procedure, the wishes of the patient, the desire of the operator for a compliant patient, and safety. Many patients are prepared to undergo upper digestive endoscopy using throat spray without sedation, while fewer accept unsedated colonoscopy. There are clinical advantages as well as disadvantages in employing sedation and sometimes general anaesthesia is the preferred option. This paper provides an introduction to the choices available and the approaches that are employed in endoscopic sedation practice.

The Calcium Carbonate Breath Test, a noninvasive test of stimulated gastric acid secretion: preliminary communication.

BACKGROUND: Gastric acid secretion is subject to complex control mechanisms, and varies widely between individuals and populations. Its measurement has previously required intubation of the stomach with ingestion of a test meal or injection of a secretion stimulant. AIM: We describe a novel method of measuring gastric acid secretion noninvasively - the Calcium Carbonate Breath Test. METHODS: 13C-labelled calcium carbonate is ingested by a fasting participant. The carbonate neutralizes gastric acid to produce 13CO2, which is expired in the breath. Measurement of the excess 13CO2 in the breath allows back-calculation of the amount of gastric acid secreted during the test, provided that other variables affecting CO2 production and excretion are minimized or controlled for. RESULTS: Studies on a single healthy individual have shown reproducible estimations of acid secretion and over 80% suppression of acid secretion after the proton pump inhibitor treatment. CONCLUSION: The method seems to be promising, but further studies on other individuals need to be carried out. The Calcium Carbonate Breath Test may have wide applications in epidemiological studies, clinical management of acid-related diseases, screening for hypochlorhydria and development of new acid-suppressing treatments.

Irritable bowel syndrome: a 10-yr natural history of symptoms and factors that influence consultation behavior.

OBJECTIVE: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. The natural history of the condition has been studied extensively, but few studies have examined factors that predict its new onset or health care-seeking behavior. METHODS: Individuals, now aged 50-59 yr, originally enrolled in a population-screening program for Helicobacter pylori (H. pylori) were contacted via postal questionnaire, utilizing the Manning criteria for IBS diagnosis. Baseline demographic data, quality of life, and IBS and dyspepsia symptom data were already on file. Consent to examine primary care records was sought, and data regarding IBS- and dyspepsia-related consultations were extracted. RESULTS: Of 8,407 individuals originally involved, 3,873 (46%) provided symptom data at baseline and 10-yr follow-up. Of 3,659 individuals without IBS at baseline, 542 (15%) developed new-onset IBS at 10-yr follow-up. After multivariate logistic regression, lower quality of life at baseline (odds ratio [OR] 4.41, 99% confidence interval [CI] 2.92-6.65), dyspepsia at baseline (OR 1.77, 99% CI 1.28-2.46), and female gender (OR 2.14, 99% CI 1.56-2.94) were significant risk factors for new-onset IBS. Of 651 individuals with IBS at either baseline or 10-yr follow-up, 113 (17%) consulted a primary care physician with symptoms. H. pylori infection (OR 1.93, 99% CI 1.03-3.62) and any dyspepsia-related consultation (OR 2.14, 99% CI 1.15-4.00) significantly increased the likelihood of consultation. CONCLUSIONS: Poor quality of life at baseline was a strong predictor of new-onset IBS, but not of IBS-related consultation behavior, which was associated with consultation for dyspepsia during the study period.

Effect of sibling number in the household and birth order on prevalence of Helicobacter pylori: a cross-sectional study.

BACKGROUND: Infection with Helicobacter pylori (H. pylori) is acquired mainly in childhood, with studies demonstrating this is related to living conditions. Effects of sibling number and birth order on prevalence of infection have not been extensively studied. METHODS: The authors performed a cross-sectional survey of adults, aged between 50 and 59 years, previously involved in a community-screening programme for H. pylori in Leeds and Bradford, UK. Prevalence of H. pylori was assessed at baseline with urea breath test. All individuals who were alive, and could be traced, were contacted by postal questionnaire in 2003 obtaining information on number of siblings and birth order. Data concerning childhood socioeconomic conditions were stored on file from the original study. RESULTS: 3928 (47%) of 8407 original participants provided data. Prevalence of infection increased according to sibling number (20% in those with none vs 63% with eight or more). Controlling for childhood socioeconomic conditions and birth order using multivariate logistic regression, infection odds were substantially increased with three siblings compared with none [odds ratio (OR) 1.51; 95% confidence interval (CI) 1.06-2.15], and a gradient of effect continued up to eight or more siblings (OR 5.70; 95% CI 2.92-11.14). Odds of infection also increased substantially with birth order, but the positive gradient disappeared on adjustment for sibling number and childhood socioeconomic conditions. CONCLUSIONS: : In this cross section of UK adults, aged 50-59 years, sibling number in the household, but not birth order, was independently associated with prevalence of H. pylori infection.

Who consults with dyspepsia? Results from a longitudinal 10-yr follow-up study.

OBJECTIVE: Dyspepsia is common, and the condition is often chronic, with a relapsing and remitting nature. Factors influencing the decision to consult a physician with symptoms remain unclear. METHODS: The authors conducted a 10-yr follow-up longitudinal survey of individuals originally involved in a community-screening program for Helicobacter pylori (H. pylori). All surviving, traceable participants were contacted by validated postal dyspepsia questionnaire. Baseline demographic data, dyspepsia and irritable bowel syndrome (IBS) symptom data, and quality of life at study entry were already on file. Consent to examine primary care records was requested, and data regarding nonsteroidal anti-inflammatory drug and aspirin use, and dyspepsia and IBS-related consultations over the 10-yr study period were extracted from these. RESULTS: Of 8,407 individuals originally involved, 3,266 (39%) gave consent to examination of primary care records. The mean age of included individuals was 55 yr, and 1,467 (45%) were male. 1,738 (53%) had dyspepsia, and 729 (42%) of these consulted a primary care physician as a result. Following multivariate logistic regression, H. pylori infection (odds ratio [OR] 1.76, 99% confidence interval [CI] 1.30-2.39), lower socioeconomic status (OR 1.68, 99% CI 1.02-2.76), frequent (OR 2.61, 99% CI 1.69-4.01) or severe (OR 1.87, 99% CI 0.99-3.52) symptoms, and increasing age (OR per year 1.06, 99% CI 1.0-1.11) were independent risk factors for consultation. CONCLUSIONS: Reasons for consulting a physician with dyspepsia are multifactorial, but H. pylori infection, lower socioeconomic status, frequent or severe symptoms, and increasing age are independent predictors of consultation.

Initial poor quality of life and new onset of dyspepsia: results from a longitudinal 10-year follow-up study.

BACKGROUND: Numerous studies examining the prevalence and natural history of dyspepsia in the general population have been conducted. However, few have reported the effect of quality of life on the development of dyspepsia. A 10-year longitudinal follow-up study examining the effect of quality of life on subsequent dyspepsia was performed. METHODS: Individuals originally enrolled in a population-screening programme for Helicobacter pylori were contacted through a validated postal dyspepsia questionnaire. Baseline demographic data, quality of life at original study entry, and dyspepsia and irritable bowel syndrome (IBS) symptom data were already on file. Consent to examine primary-care records was sought, and data regarding non-steroidal anti-inflammatory drugs (NSAID) and aspirin use were obtained from these. RESULTS: Of 8407 individuals originally involved, 3912 (46.5%) provided symptom data at baseline and 10-year follow-up. Of 2550 (65%) individuals asymptomatic at study entry, 717 (28%) developed new-onset dyspepsia at 10 years, an incidence of 2.8% per year. After multivariate logistic regression, lower quality of life at study entry (OR 2.63; 99% CI 1.86 to 3.71), higher body mass index (OR per unit 1.05; 99% CI 1.02 to 1.08), presence of IBS at study entry (OR 3.1; 99% CI 1.51 to 6.37) and use of NSAIDs and/or aspirin (OR 1.32; 99% CI 0.99 to 1.75) were significant risk factors for new-onset dyspepsia. CONCLUSIONS: The incidence of new-onset dyspepsia was almost 3% per year. Low quality of life at baseline exerted a strong effect on the likelihood of developing dyspepsia at 10 years.

Randomized crossover study that used methylene blue or random 4-quadrant biopsy for the diagnosis of dysplasia in Barrett's esophagus.

BACKGROUND: Barrett's esophagus is generally accepted to be a premalignant condition. Previous studies have suggested the use of methylene blue (MB) chromoendoscopy to aid the identification of dysplasia in Barrett's esophagus surveillance programs, but a recent study has raised the concern that MB might induce oxidative damage of DNA. OBJECTIVE: The aim of this study was to compare MB directed biopsies (MBDB) with our current standard, which is random 4 quadrant biopsies (RB). DESIGN: A randomized prospective crossover study. SETTING: Single center. PATIENTS: Patients with a diagnosis of dysplasia identified in Barrett's esophagus within a 2-year period before entering the study. INTERVENTIONS: Either 4 random quadrant biopsies taken every 2 cm through the length of the Barrett's esophagus or MBDB from unstained or heterogenously stained mucosa. MAIN OUTCOME MEASUREMENTS: The number of patients with a diagnosis of dysplasia by each intervention. LIMITATIONS: Thirty-six percent of eligible patients declined the invitation to participate. RESULTS: Thirty patients completed the crossover study. The median length of Barrett's esophagus was 5 cm (interquartile range [IQR] 3-9 cm). At baseline histology, grades were as follows: 17 low-grade dysplasia (LGD), 3 high-grade dysplasia (HGD), and 10 no dysplasia. At completion, there were 10 LGD, 8 HGD, and 12 no dysplasia. Overall, dysplasia was identified in 17 of 18 patients by RB and in 9 of 18 by MBDB (McNemar test, p = 0.02). CONCLUSIONS: Our study showed MBDB to be significantly less sensitive in detecting dysplasia than RB in Barrett's esophagus. Hence, we discourage its use during routine surveillance of Barrett's esophagus.

A community screening program for Helicobacter pylori saves money: 10-year follow-up of a randomized controlled trial.

BACKGROUND & AIMS: Population screening and treatment of Helicobacter pylori has been advocated as a means of reducing mortality from gastric cancer, as well as dyspepsia and dyspepsia-related resource use. Previous programs have failed to demonstrate a significant effect on mortality or resource use, but follow-up was only for 1 or 2 years. We aimed to determine the effect of screening for H pylori on dyspepsia and dyspepsia-related resource use over 10 years. METHODS: H pylori-positive individuals, aged 40-49 years, enrolled in a community screening program, randomized to eradication therapy or placebo in 1994, were sent a validated dyspepsia questionnaire by mail 10 years later, and primary care records were reexamined. Consultation, referral, prescribing, and investigation data related to dyspepsia were extracted. United Kingdom costs were applied to derive total cost per person (1 pound = 1.8 dollars). RESULTS: Of 2324 original participants, 1864 (80%) were traced and contacted. Of these, 1086 (47%) responded, and 919 (40%) agreed to a review of their primary care records. There was a 10-year mean saving in total dyspepsia-related costs of 117 dollars per person (95% confidence interval [CI] = 11 dollars-220 dollars, P = .03) with eradication therapy. Those symptomatic at baseline showed a nonsignificant trend toward resolution of symptoms at 10 years with eradication therapy (relative risk of remaining symptomatic, 0.89; 95% CI: 0.77-1.03). CONCLUSIONS: There were significant reductions in total dyspepsia-related health care costs. The savings made were greater than the initial cost of H pylori screening and treatment.

Cost-effectiveness and long-term impact of Helicobacter pylori 'test and treat' service in reducing open access endoscopy referrals.

INTRODUCTION: We have shown that the introduction of a carbon urea breath test (13C-UBT) service for Helicobacter pylori screening and eradication is effective in reducing the rate of open access endoscopy referrals in patients aged < 40 years in the short term. This has been substantiated by several randomized controlled trials comparing a 'test and treat' strategy with early endoscopy in these patients. However, the long-term impact of such a strategy is not established. OBJECTIVE: To ascertain the influence of 13C-UBT services on open access endoscopy referral rates in dyspeptic patients under the age of 40 years over a period of 5 years. METHODS: Retrospective analysis of open access endoscopy referral rates between August 1990 and July 2000. Cost minimization analysis was performed with a Decision Analysis Model using Treeage Data 3.5. RESULTS: The total number of open access referrals for endoscopy during 1990-1995 was between 765 and 1325 per year. The proportion of endoscopies performed in patients < 40 years ranged between 33.4% and 34.6%. The total number of endoscopy referrals during 1995-2000 after the introduction of the 13C-UBT services was between 1178 and 1321 per year. However, there was a sustained reduction in the proportion of patients aged < 40 years, ranging between 23.2% and 26.2% (Chi2 = 153.9, degrees of freedom = 9, P < 0.0001) during this period. CONCLUSIONS: The H. pylori screening and treatment strategy using the 13C-UBT service results in a sustained reduction of the number of endoscopy referrals and is cost effective in dyspeptic patients under the age of 40 years, enabling better utilization of available resources.

Relation of adult lifestyle and socioeconomic factors to the prevalence of Helicobacter pylori infection.

INTRODUCTION: The influence of adult socioeconomic status, co-habitation, gender, smoking, coffee and alcohol intake on risk of Helicobacter pylori infection is uncertain. METHODS: Subjects between aged 40-49 years were randomly invited to attend their local primary care centre. Participants were interviewed by a researcher on smoking, coffee and alcohol intake, history of living with a partner, present and childhood socioeconomic conditions. Helicobacter pylori status was determined by 13C-urea breath test. RESULTS: In all, 32 929 subjects were invited, 8429 (26%) were eligible and 2327 (27.6%) were H. pylori positive. Helicobacter pylori infection was more common in men and this association remained after controlling for childhood and adult risk factors in a logistic regression model (odds ratio [OR] = 1.15; 95% CI: 1.03-1.29). Living with a partner was also an independent risk factor for infection (OR = 1.30; 95% CI: 1.01-1.67), particularly in partners of lower social class (social class IV and V-OR = 1.47; 95% CI: 1.19-1.81, compared with social class I and II). Helicobacter pylori infection was more common in lower social class groups (I and II-22% infected, III-29% infected, IV and V-38% infected) and there was a significant increase in risk of infection in manual workers compared with non-manual workers after controlling for other risk factors (OR = 1.18; 95% CI: 1.03-1.34). Alcohol and coffee intake were not independent risk factors for infection and smoking was only a risk factor in those smoking >35 cigarettes a day. CONCLUSIONS: Male gender, living with a partner and poor adult socioeconomic conditions are associated with increased risk of H. pylori infection.

Antioxidant vitamin supplements do not reduce reactive oxygen species activity in Helicobacter pylori gastritis in the short term.

Reactive oxygen species have been implicated in Helicobacter pylori-mediated gastric carcinogenesis, whereas diets high in antioxidant vitamins C and E are protective. We have examined the effect of vitamin C and E supplements in combination with H. pylori eradication on reactive oxygen species activity in H. pylori gastritis. H. pylori-positive patients were randomized into four groups: triple therapy alone (Bismuth chelate, tetracycline, and metronidazole for 2 weeks), vitamins alone (200mg vitamin C and 50mg vitamin E, both twice per day for 4 weeks), both treatments or neither. Plasma and mucosal ascorbic acid, malondialdehyde and reactive oxygen species were determined before and after treatment. Compared with normal controls (n 61), H. pylori-positive patients (n 117) had higher mucosal reactive oxygen species and malondialdehyde levels and lower plasma ascorbic acid. Plasma ascorbic acid doubled in both groups of patients receiving vitamins and mucosal levels also increased. Malondialdehyde and reactive oxygen species fell in patients in whom H. pylori was eradicated but vitamin supplements were not effective either alone or in combination with H. pylori eradication. Supplements of vitamins C and E do not significantly reduce mucosal reactive oxygen species damage in H. pylori gastritis.

ADAMs (a disintegrin and metalloproteinase) messenger RNA expression in Helicobacter pylori-infected, normal, and neoplastic gastric mucosa.

Helicobacter pylori is a risk factor for gastric cancer, and bacterial-epithelial interactions may be critical in this association. Studies using complementary DNA arrays indicated that the ADAM (A disintegrin and metalloproteinase) genes in gastric epithelial cells are differentially expressed after bacterial-epithelial interactions. Reverse-transcription polymerase chain reaction analysis of gastric biopsy specimens from patients with and without H. pylori showed that infection was associated with increased expression of ADAM 10 and ADAM 17 (tumor necrosis factor-alpha-converting enzyme) in antral mucosa, but no increases in ADAM 15 and ADAM 20 were observed. Increased ADAM 10 transcripts were observed only in cagA-negative infections. High levels of ADAM 10, ADAM 17, and ADAM 20 transcripts were present in gastric carcinoma. H. pylori stimulated temporal changes in ADAM 10 and ADAM 17 transcripts in gastric epithelial cells. Chronic infection with H. pylori may result in persistent mucosal increases in members of the ADAMs family. ADAMs-mediated ectodomain shedding may have a role in gastric carcinogenesis.