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C O'Morain

Publications and source records attributed to C O'Morain.

At least 37 records · Page 2Linked to original sources

Helicobacter pylori-induced duodenal ulcer frequently coincides with gastro-oesophageal reflux disease.

BACKGROUND: The relationship between Helicobacter pylori infection and gastro-oesophageal reflux disease is complicated. Evidence does not support a causal link. There have been reports, which have implicated successful eradication of Helicobacter pylori, in patients with a duodenal ulcer, with the subsequent development of gastro-oesophageal reflux disease. However, eradication of Helicobacter pylori in these patients with improvement in their condition and a return to normal lifestyle, weight gain and discontinuation of antacids may unmask pre-existing gastro-oesophageal reflux disease. AIMS: To determine the true prevalence of gastro-oesophageal reflux disease in patients with Helicobacter pylori-related duodenal ulceration. METHOD: Dyspeptic patients undergoing endoscopy were prospectively screened for the presence of a duodenal ulcer. Concomitant oesophagitis, when present, was recorded. All subjects with a Helicobacter pylori-related duodenal ulcer without endoscopic evidence of gastro-oesophageal reflux disease were invited to undergo a 24-hr ambulatory oesophageal pH assessment prior to receiving treatment. RESULTS: A total of 97 patients with a duodenal ulcer were identified and 83.5% were Helicobacter pylori positive. Overall, 27.8% had associated endoscopic evidence of oesophagitis, 70% grade I-II and 30% grade III-IV. Of those without evidence of oesophagitis at endoscopy, 68% underwent a 24-hr pH assessment. An additional 17% were identified by this means as having gastro-oesophageal reflux disease. Overall, 44% of symptomatic subjects with Helicobacter pylori and a duodenal ulcer were found to have coexistent gastro-oesophageal reflux disease. CONCLUSION: Gastro-oesophageal reflux disease is frequently found to coexist with Helicobacter pylori-related duodenal ulcer. In addition, almost 20% of symptomatic patients without endoscopic evidence of oesophagitis will have an abnormal oesophageal pH exposure. It is plausible that the development of gastro-oesophageal reflux disease following successful eradication of Helicobacter pylori represents unmasking of existing disease rather than de novo development.

Adolescent↗

Current concepts in the management of Helicobacter pylori infection--the Maastricht 2-2000 Consensus Report.

Significant progress and new insights have been gained in the 4 years since the first Maastricht Consensus Report, necessitating an update of the original guidelines. To achieve this, the European Helicobacter Pylori Study Group organized a meeting of specialists and experts from around the world, representatives from National Gastroenterology Societies and general practitioners from Europe to establish updated guidelines on the current management of Helicobacter pylori infection. The meeting took place on 21-22 September 2000. A "test and treat" approach is recommended in adult patients under the age of 45 years (the age cut-off may vary locally) presenting in primary care with persistent dyspepsia, having excluded those with predominantly gastro-oesophageal reflux disease symptoms, non-steroidal anti-inflammatory drug users and those with alarm symptoms. Diagnosis of infection should be by urea breath test or stool antigen test. As in the previous guidelines, the eradication of H. pylori is strongly recommended in all patients with peptic ulcer, including those with complications, in those with low-grade gastric mucosa-associated lymphoid tissue lymphoma, in those with atrophic gastritis and following gastric cancer resection. It is also strongly recommended in patients who are first-degree relatives of gastric cancer patients and according to patients' wishes after full consultation. It is advised that H. pylori eradication is considered to be an appropriate option in infected patients with functional dyspepsia, as it leads to long-term symptom improvement in a subset of patients. There was consensus that the eradication of H. pylori is not associated with the development of gastro-oesophageal reflux disease in most cases, and does not exacerbate existing gastro-oesophageal reflux disease. It was agreed that the eradication of H. pylori prior to the use of non-steroidal anti-inflammatory drugs reduces the incidence of peptic ulcer, but does not enhance the healing of gastric or duodenal ulcer in patients receiving antisecretory therapy who continue to take non-steroidal anti-inflammatory drugs. Treatment should be thought of as a package which considers first- and second-line eradication therapies together. First-line therapy should be with triple therapy using a proton pump inhibitor or ranitidine bismuth citrate, combined with clarithromycin and amoxicillin or metronidazole. Second-line therapy should use quadruple therapy with a proton pump inhibitor, bismuth, metronidazole and tetracycline. Where bismuth is not available, second-line therapy should be with proton pump inhibitor-based triple therapy. If second-line quadruple therapy fails in primary care, patients should be referred to a specialist. Subsequent failures should be handled on a case-by-case basis by the specialist. In patients with uncomplicated duodenal ulcer, eradication therapy does not need to be followed by further antisecretory treatment. Successful eradication should always be confirmed by urea breath test or an endoscopy-based test if endoscopy is clinically indicated. Stool antigen test is the alternative if urea breath test is not available.

Adult↗

Does Helicobacter pylori eradication affect symptoms in nonulcer dyspepsia: a 5-year follow-up study.

The role of Helicobacter pylori infection in nonulcer dyspepsia remains controversial. To date studies exploring the effect of H. pylori eradication on symptoms have reported conflicting results. Randomised control trials employing validated outcome measures have also been difficult to interpret because of several important issues such as the large placebo response seen in patients with nonulcer dyspepsia and both the natural variability in symptoms and symptom severity with time. The association of symptom improvement with resolution of gastritis has meant that the length of follow up employed in most studies has been insufficient. We report the findings of a randomised placebo controlled trial (n = 100), using a validated symptom questionnaire and 5 year follow up to determine the effect of H. pylori eradication on symptoms in nonulcer dyspepsia. In all 64 that were reviewed at 5 years there was a significant difference between patients who were H. pylori negative and those who remained positive with regard to complete symptom resolution, consumption of relevant medications and peptic ulcer disease development, in favour of active treatment. There was a trend for gradual symptom improvement over time irrespective of H. pylori status, which may reflect the natural history of this condition. For those who remained symptomatic at 5 years, there was no difference in symptom severity based on H. pylori status. The findings of this study support the use of H. pylori eradication in symptomatic patients with nonulcer dyspepsia both to induce symptom resolution and to prevent disease progression.

Adolescent↗

Carditis: all Helicobacter pylori or is there a role for gastro-oesophageal reflux?

BACKGROUND: Recent epidemiological studies have reported a threefold increase in the incidence of adenocarcinoma of the lower oesophagus and gastro-oesophageal junction (cardia). There are conflicting reports available implicating both gastro-oesophageal reflux disease and Helicobacter pylori infection in the aetiology of carditis and cardia intestinal metaplasia, despite strong evidence to show that these two conditions are, if anything, inversely related. We aimed to determine the prevalence of carditis and cardia intestinal metaplasia in dyspeptic subjects and also their association with H. pylori infection and gastro-oesophageal reflux disease. METHOD: Histological samples from the gastric cardia were obtained from dyspeptic subjects. H. pylori status was assessed based on histological, microbiological and rapid urease testing. Gastro-oesophageal disease was diagnosed on the basis of histological evidence and/or erosive oesophagitis. Patient demographics were recorded. Cardia intestinal metaplasia (CIM), when present, was subgrouped as complete or incomplete. RESULTS: Overall, 276 subjects were enrolled; 163 (59%) had carditis and 36 (13%) CIM. H. pylori infection and gastro-oesophageal reflux disease occurred in 64 (23%) and 150 (54%), respectively. H. pylori infection was strongly associated with carditis and CIM (P<0.001 and P<0.01). Older age and male gender were also associated with inflammation and intestinal metaplasia of the cardia. Gastro-oesophageal reflux was not associated with either entity. CONCLUSION: Carditis and CIM occur frequently. Both conditions are strongly associated with H. pylori infection, older age and male gender. There was no association with gastro-oesophageal reflux disease.

Adolescent↗

Review article: non-steroidal anti-inflammatory drugs and Helicobacter pylori.

Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori are well-recognized causes of gastroduodenal mucosal damage. This damage is mediated through the effects of both agents on acid secretion, neutrophil activity and function, and prosta- glandin metabolism. Clinical trials on the interrelation- ship between H. pylori, NSAIDs and gastroduodenal mucosal injury have yielded conflicting results. No consensus has been reached on what recommenda- tions should be implemented with regard to H. pylori eradication in patients on long-term NSAID therapy. At present, the presence of H. pylori is identified at endoscopy and eradication is carried out in symptomatic patients. Asymptomatic patients remain a dilemma that requires further investigation. Clinical practice will continue to be tailored to a patient's individual requirements. Therefore, in patients at risk of gastrointestinal haemorrhage, and on NSAID therapy, acid suppression therapy should be prescribed.

Anti-Inflammatory Agents, Non-Steroidal↗

Challenges to therapy in the future.

Quadruple therapy (with a proton pump inhibitor (PPI), metronidazole, tetracycline and bismuth) is generally reserved for second-line treatment; however, studies using this regimen for 7 days have found it to be effective even in metronidazole-resistant strains. Resistance is an ongoing problem with antimicrobial therapy but considerable progress has now been made into understanding the underlying genetic mechanisms of this process. Metronidazole resistance in Europe is usually in the range of 20-30% of strains but may be as high as 70% in some countries. One genetic mechanism involved is thought to be a mutation of the rdxA gene. Macrolide resistance appears to be on the increase in Europe, varying from 1% in some countries to 13% in others. The genetic mechanism involved has been shown to be a point mutation of a ribosomal RNA. Amoxicillin resistance is an emerging problem that has an adverse effect on eradication rates in clinical practice. Resistance has been shown to be caused by the absence of one of the four binding proteins in the cell wall. Few novel antibiotics have been developed for use in eradication therapy, although rifabutin, secnidazole and furazolidone have shown some success as part of combination therapy. Alternative therapies that have been tested include mucosal protective agents which have been used in place of a PPI in some eradication regimens with some success, and the somatostatin analog, octreotide, that has been used as part of quadruple therapy in place of a PPI and produced eradication rates of approximately 88%. The ultimate challenge is still to develop a safe and effective vaccine against Helicobacter pylori. Current and future research will also focus on identifying genetic targets for therapy, adhesion molecule analogs to prevent binding of the bacterium, and urease inhibitors. The current triple therapy treatment options available for the eradication of Helicobacter pylori infection are over 90% effective in susceptible organisms and there are very few medical conditions to which we can offer such efficacious treatment. Unfortunately, the recommendations made at consensus conferences are not always put into practice and physicians in primary care may be unaware of the true efficacy of eradication therapy. Treatment is very simple: three drugs, twice a day for 1 week. The main focus for both primary care physicians and gastroenterologists should be to reinforce the need for patient compliance, otherwise we will see an increase in antibiotic resistance. Patients should be prewarned that they may experience some mild side effects and should be encouraged to complete the course of treatment. The real challenge for the future will be the management of patients who do not respond to first-line treatment. This paper will focus on potential problems with therapy, such as antibiotic resistance, and possible future solutions, such as novel antibiotics and vaccines.

Anti-Bacterial Agents↗

Comparison of tests for assessment of Helicobacter pylori eradication: results of a multi-centre study using centralized facility testing.

BACKGROUND: The accuracy of diagnostic tests to assess Helicobacter pylori eradication has rarely been performed. AIM: To compare the tests most commonly used for this purpose, i.e. histology, culture and (13)C urea breath test performed in centralized facilities. METHODS: Prospective study where patients were included in four centres and diagnostic tests performed centrally by biologists experienced in the field. Gastric biopsies were obtained from antrum and corpus (two for histology, two for culture from each site) 4-6 weeks after an eradication treatment. The definition of a gold standard for H. pylori-positive patients was either a positive culture or both positive histology and urea breath test results. RESULTS: Ninety-seven patients for whom data on histology, culture and (13)C urea breath test were available were included. The majority were females (60%) suffering from non-ulcer dyspepsia (52%) and having received proton-pump inhibitor-based triple therapy (62%). Forty-one per cent of the patients were H. pylori-positive according to the gold standard. The sensitivities were 90%, 95% and 92.5% and the specificities 100%, 98.2% and 100% for culture, histology and (13)C urea breath test, respectively. CONCLUSION: All the methods had excellent specificity but the sensitivity ranged between 90 and 95%. The combination of two techniques which increases the sensitivity to virtually 100% is recommended in situations where the eradication treatment requires a precise evaluation such as in clinical trials.

Breath Tests↗

Noninvasive antigen-based assay for assessing Helicobacter pylori eradication: a European multicenter study. The European Helicobacter pylori HpSA Study Group.

OBJECTIVE: In a recently published multicenter study involving 501 patients undergoing esophagogastroduodenoscopy (EGD) throughout Europe, we showed the high accuracy of a recently developed simple test (HpSA) to detect Helicobacter pylori (H. pylori) antigens in stools of untreated patients. The aim of this study was to assess the diagnostic usefulness of HpSA compared with 13C UBT shortly after H. pylori eradication treatment. METHODS: Of the 501 patients enrolled in the validation study, 279 were found to be H. pylori-positive. These patients were given H. pylori eradicating regimen and asked to return for follow-up EGD with biopsies, 13C UBT and HpSA testing 4 wk after therapy. Follow-up results were available for 235 patients. Of these, 162 consented to all testing and 73 consented only to 13C UBT and HpSA testing. We assessed sensitivity and specificity of both HpSA and 13C UBT compared with biopsy-based methods in the 162 patients, who accepted follow-up EGD. We also assessed sensitivity and specificity of HpSA compared with 13C UBT, arbitrarily chosen as the gold standard, in the whole population of 235 patients. RESULTS: Sensitivity and specificity in 162 patients who consented to a second EGD were 93.8% (CI: 85.4-100%) and 96.9% (CI: 93.9-99.9%) for HpSA, and 90.6% (CI: 80.5-100%) and 99.2% (CI: 97.7-100%) for UBT. Using EGD-based methods as the gold standard, 130 of the 162 treated patients' H. pylori infection were eradicated (125 HpSA-negative, one borderline, and four false-positive; 129 13C UBT-negative, one false-positive), and 32 remained H. pylori-infected (30 HpSA-positive, two false-negative, 29 13C UBT-positive, three false negative). The overall eradication rate was 80.2%. The sensitivity and specificity of HpSA relative to UBT as the gold standard in the overall population (n = 235) were 95.6% (CI: 89.6-100%) and 94.7% (CI: 91.5-97.9%), respectively. CONCLUSIONS: HpSA has proven to be a useful method in posttreatment eradication testing for H. pylori. Its ease of use, speed, and noninvasive nature make HpSA testing an ideal method for post-treatment monitoring where a second EGD may not be justified.

Adult↗

Consensus guidelines: agreement and debate surrounding the optimal management of Helicobacter pylori infection.

Helicobacter pylori is a recognized cause of a variety of gastroduodenal pathology. The high prevalence of both H pylori infection and related diseases within the community warrants its consideration as a public health care issue. The availability of reliable and safe noninvasive diagnostic techniques coupled with the development of effective and tolerable treatments has enabled primary health care personnel to manage this infection actively. The role of the primary care physician in the future management of H pylori infection is thus of central importance. The wealth of evidence produced by over 15 years of research into H pylori has expanded the list of disease associations and treatment benefits as well as elucidated the pathophysiological mechanisms involved. As a result, there has been a growing need to harmonize this information with clinical practice and to provide direction for the appropriate management by both specialists and general practitioners. Several national guidelines have been produced. The areas relating to H pylori infection that they considered and their recommendations vary. In 1994, the National Institutes of Health produced globally accepted recommendations for the management of H pylori-related peptic ulceration. The broader role of H pylori as a gastroduodenal pathogen and a public health care issue was not addressed. Recently, European and Canadian consensus guidelines have been published that identified overall management issues, including the role of primary and specialist care, and considered the appropriateness of employing eradication therapy for the spectrum of conditions in which H pylori has a direct or indirect association based on the available information. These guidelines, while in agreement regarding many issues, differ considerably in their recommendations for primary health care and regarding central issues such as the management of dyspepsia and gastric cancer. Some variations may reflect differing health care structures as well as the prevalence of both infection and associated diseases. However, the interpretation of evidence produced by recent research contributes to their conflicting statements.

Canada↗

Diagnosis of Helicobacter pylori infection with a new non-invasive antigen-based assay. HpSA European study group.

BACKGROUND: Helicobacter pylori is a common human pathogen implicated in certain gastrointestinal diseases. In the search for new non-invasive techniques to diagnose H. pylori infection, we evaluated an EIA for H. pylori antigen in stool (HpSA). METHODS: In a prospective multicentre study, stool specimens from 501 patients (276 men, 225 women; age range 17-88 years, mean 52) undergoing gastroscopy in 11 centres throughout Europe were tested with HpSA and the carbon-13-urea breath test. At endoscopy, four biopsy samples were taken for histology (haematoxylin and eosin) and H. pylori detection (giemsa in both antrum and corpus, culture and rapid urease test). Patients were defined as positive for H. pylori if histology (antrum, corpus, or both) and urease test were positive, or if culture was positive. Patients classified as having H. pylori infection received an eradication regimen; 107 were reassessed 4 weeks after therapy. FINDINGS: Of 272 patients with H. pylori infection by the predefined criteria, 256 were positive by HpSA (sensitivity 94.1% [95% CI 90.6-96.6]). Of 219 patients without infection, 201 were negative by HpSA (specificity 91.8% [87.3-95.1]). INTERPRETATION: The stool assay was a reliable and easy-to-use tool for diagnosis of H. pylori infection. The test was accurate even shortly after treatment.

Adolescent↗

The DU-MACH study: eradication of Helicobacter pylori and ulcer healing in patients with acute duodenal ulcer using omeprazole based triple therapy.

AIM: To investigate the efficacy of two omeprazole triple therapies for the eradication of Helicobacter pylori, ulcer healing and ulcer relapse during a 6-month treatment-free period in patients with active duodenal ulcer. METHODS: This was a double-blind, randomized study in 15 centres across Canada. Patients (n = 149) were randomized to omeprazole 20 mg once daily (O) or one of two 1-week b. d. eradication regimens: omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg (OMC) or omeprazole 20 mg, amoxycillin 1000 mg and clarithromycin 500 mg (OAC). All patients were treated for three additional weeks with omeprazole 20 mg once daily. Ulcer healing was assessed by endoscopy after 4 weeks of study therapy. H. pylori eradication was determined by a 13C-urea breath test and histology, performed at pre-entry, at 4 weeks after the end of all therapy and at 6 months. RESULTS: The intention-to-treat (intention-to-treat) analysis contained 146 patients and the per protocol (per protocol) analysis, 114 patients. The eradication rates were (intention-to-treat/per protocol): OMC-85% and 92%, OAC-78% and 87% and O-0% (O). Ulcer healing (intention-to-treat) was greater than 90% in all groups. The differences in the eradication and relapse rates between O vs. OMC and O vs. OAC were statistically significant (all, P < 0.001). Treatment was well tolerated and compliance was high. CONCLUSION: The OMC and OAC 1-week treatment regimens are safe and effective for eradication, healing and the prevention of relapse in duodenal ulcer patients.

Acute Disease↗

The GU-MACH study: the effect of 1-week omeprazole triple therapy on Helicobacter pylori infection in patients with gastric ulcer.

AIMS: To study the efficacy of omeprazole triple therapy in the eradication of Helicobacter pylori in patients with active gastric ulcer, and to assess healing and relapse of gastric ulcer. METHODS: A double-blind, randomized study was carried out in 18 centres in Germany, Hungary and Poland. Patients (n = 160) with gastric ulcer and a positive H. pylori screening test were randomized to a 7-day twice daily treatment with omeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1000 mg (OAC) or omeprazole 20 mg, clarithromycin 250 mg and metronidazole 400 mg (OMC), or with omeprazole 20 mg once daily (O). After completion of this 1-week treatment, patients were treated with omeprazole until healing (maximum 12 weeks), and followed for 6 months. H. pylori was assessed by urea breath test (UBT) and histology. RESULTS: Eradication rates ITT were OAC 79% (95% CI: 65-90%), OMC 86% (95% CI: 73-94%) and O 4% (95% CI: 0-14%). Eradication rates PP were OAC 83% (95% CI: 68-93%), OMC 93% (95% CI: 80-98%) and O 3% (95% CI: 0-13%). Gastric ulcer relapses occurred in 5, 0 and 11 patients in the groups, respectively. CONCLUSIONS: The results from the study demonstrate that OMC and OAC 1-week regimens are safe and effective for eradication of H. pylori in gastric ulcer patients, and that ulcer relapse is infrequent after successful eradication.

Adult↗

Omeprazole, amoxycillin and metronidazole for the cure of Helicobacter pylori infection.

OBJECTIVE: In two studies, different regimens of omeprazole-amoxycillin-metronidazole were assessed for the eradication of Helicobacter pylori. DESIGN: Randomized, international, multicentre studies with parallel groups. SETTING: The studies were performed at centres in Canada, Czech Republic, France, Germany, Hungary, Sweden and UK. PARTICIPANTS AND INTERVENTIONS: H. pylori-positive patients with duodenal ulcer disease (active or in remission) were randomized to 7-day treatment with: omeprazole 40 mg once daily, amoxycillin 500 mg three times daily and metronidazole 400 mg three times daily (OAMtid; n = 242); omeprazole 20 mg twice daily, amoxycillin 1000 mg twice daily and metronidazole 800 mg twice daily (OAM800; n = 247); or omeprazole 20 mg twice daily, amoxycillin 1000 mg twice daily and metronidazole 400 mg twice daily (OAM400; n = 127). MAIN OUTCOME MEASURES: Eradication of H. pylori. RESULTS: Intention-to-treat analysis revealed H. pylori eradication rates of 76% (184/242) with OAMtid, 80% (198/247) with OAM800, and 76% (97/127) with OAM400. There was considerable variation in the levels of primary resistance to metronidazole in different countries. The overall eradication rate in patients infected with metronidazole-sensitive H. pylori strains was 85% (313/370), compared with 60% (56/94) in patients harbouring metronidazole-resistant strains (P<0.001). All regimens were generally well tolerated, with mild adverse events occurring in 4-26% of patients (mainly diarrhoea, reversible increase in liver enzymes and headache). CONCLUSION: The OAM combination is effective in curing H. pylori infection. Primary metronidazole resistance may reduce its effectiveness, but an increased daily dosing of metronidazole may partly overcome this problem.

Amoxicillin↗

Antimicrobial susceptibility testing of Helicobacter pylori in a large multicenter trial: the MACH 2 study.

Culture and susceptibility testing of Helicobacter pylori strains was performed in a large multinational, multicenter randomized clinical trial. Culture was carried out on gastric biopsy samples obtained from 516 patients at entry and had a sensitivity of 99% when the [(13)C]urea breath test was used as a reference. Susceptibility testing was performed for clarithromycin and metronidazole on 485 strains by an agar dilution method and the epsilometer test (Etest) and for amoxicillin by an agar dilution method only. Resistance to clarithromycin (>1 microgram/ml) was found in 3% of the H. pylori strains, with a perfect correlation between Etest and agar dilution methods. Resistance to metronidazole (>8 microliter/ml) was found in 27% of the strains by agar dilution, but there were important discrepancies between it and the Etest method. No resistance to amoxicillin was found. The logarithms of the MICs of the three antibiotics against susceptible strains had a distribution close to normal. The impact of resistance was tested in the four arms of the trial. There were not enough clarithromycin-resistant strains to evaluate the impact of resistance on the cure rate of clarithromycin-based regimens. For metronidazole-resistant strains, the impact noted in the clarithromycin-metronidazole arm was partially overcome when omeprazole was added (76% eradication for resistant strains versus 95% for susceptible strains). Secondary resistance to clarithromycin occurred in strains from 12 of 105 patients (11.4%) after the failure of a clarithromycin-based regimen to effect eradication. The detection of point mutations in clarithromycin-resistant strains was performed by a combination of PCR and restriction fragment length polymorphism. Mutations (A2142G and 2143G) were found in all strains tested except one. This study stresses the importance of performing susceptibility tests in clinical trials in order to explain the results of different treatments.

Anti-Bacterial Agents↗