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ABSTRACT: Factors other than acid may play a role in gastro-oesophageal reflux disease (GERD) and its complications.
To assessed the role of bile acids in the pathogenesis of GERD, Barrett's oesophagus and Barrett's-related neoplasia.
We conducted a systematic review of computerised bibliographic databases for original articles involving humans or human oesophageal tissue or cells that assessed exposure to or manipulation of bile acids. Outcomes assessed included GERD symptoms; gross oesophageal injury; Barrett's oesophagus and related neoplasia; and intermediate markers of inflammation, proliferation or neoplasia.
Eighty-three original articles were included. In in vivo studies, bile acids concentrations were higher in the oesophageal aspirates of patients with GERD than controls, and bile acids infusions triggered GERD symptoms, especially in high concentrations or in combination with acid. In ex vivo/in vitro studies, bile acids stimulated squamous oesophageal cells and Barrett's epithelial cells to produce inflammatory mediators (e.g., IL-8 and COX-2) and caused oxidative stress, DNA damage and apoptosis. They also induced squamous cells to change their gene expression pattern to resemble intestinal-type cells and caused Barrett's cells to increase expression of intestinal-type genes.
In aggregate, these studies suggest that bile acids may contribute to the pathogenesis of symptoms, oesophagitis and Barrett's metaplasia with related carcinogenesis in patients with GERD. However, all study results are not uniform and substantial differences in study parameters may explain at least some of this variation.
Alimentary Pharmacology & Therapeutics 07/2011; 34(2):146-65. · 3.77 Impact Factor
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ABSTRACT: Current PPIs may not achieve desired outcomes in some GERD patients due to limited duration of acid inhibition.
To evaluate a novel rabeprazole extended release (ER), which provides longer duration of drug exposure and acid suppression, in healing and symptomatic resolution of moderate-severe erosive oesophagitis.
Patients with LA grade C or D oesophagitis were randomised to rabeprazole-ER 50 mg or esomeprazole 40 mg once daily in two identical 8-week double-blind trials (N = 2130). Two primary endpoints were tested sequentially: (1) healing by 8 weeks [hypothesis: rabeprazole-ER non-inferior to esomeprazole (non-inferiority margin = 8%)], (2) healing by 4 weeks [hypothesis: rabeprazole-ER superior to esomeprazole (P < 0.05)]. The secondary endpoint was sustained heartburn resolution at 4 weeks.
Rabeprazole-ER was non-inferior to esomeprazole in week-8 healing (80.0% vs. 75.0%; 77.5% vs. 78.4%). Week-4 healing (54.8% vs. 50.3%; 50.9% vs. 50.7%) and sustained heartburn resolution (48.3% vs. 48.2%; 53.2% vs. 52.5%) were not significantly different. Post hoc combined results for grade D revealed rabeprazole-ER vs. esomeprazole differences in week-8 healing = 10.4% (95% CI: -1.4%, 22.2%) and week-4 healing = 12.0% (P = 0.048).
Rabeprazole-ER is as effective as esomeprazole in healing moderate-severe oesophagitis and achieves similar rates of heartburn resolution. Subgroup analysis suggests the possibility of benefit in severe oesophagitis, but this requires further evaluation (ClinicalTrials.gov: NCT00658528 and NCT00658775).
Alimentary Pharmacology & Therapeutics 01/2011; 33(2):203-12. · 3.77 Impact Factor
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ABSTRACT: Nonsteroidal anti-inflammatory drugs (NSAID)-related GI effects vary based on patient characteristics.
To assess risk factors for NSAID-associated upper GI clinical events and dyspepsia.
Patients ≥50 years with osteoarthritis or rheumatoid arthritis were randomized to etoricoxib or diclofenac in a prespecified intent-to-treat analysis of three double-blind randomized trials. Potential risk factors for upper GI clinical events (bleeding, perforation, obstruction, or ulcer), complicated events (perforation, obstruction, bleeding) and discontinuations due to dyspepsia were assessed with Cox proportional hazard models.
Significant predictors of clinical events and complicated events included age ≥65 years [hazards ratios (HRs) = 2.25 (1.84-2.76), 4.09 (2.82-5.92)], prior event [HRs = 2.57 (1.94-3.39), 3.23 (2.09-5.00)], low-dose aspirin [HRs = 2.34 (1.87-2.92), 3.41 (2.33-5.00)] and corticosteroid [HRs = 1.85 (1.41-2.43), 2.09 (1.29-3.38)]. Predictors of discontinuation due to dyspepsia included prior dyspepsia [HR = 1.78 (1.44-2.00)], prior event [HR = 1.78 (1.40-2.27)] and age ≥65 years [HR = 1.35 (1.16-1.57)].
Assessment for age ≥65 years, prior upper GI clinical events and low-dose aspirin use are key in identifying patients who should either avoid NSAIDs or employ management strategies to reduce NSAID-associated upper GI events. Prior dyspepsia or upper GI clinical events and age ≥65 years also predict an increased risk of developing dyspepsia severe enough to necessitate discontinuation of NSAIDs.
Alimentary Pharmacology & Therapeutics 11/2010; 32(10):1240-8. · 3.77 Impact Factor
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ABSTRACT: Protective co-therapy is recommended in NSAID users with GI risk factors, but adherence is poor.
To assess the proportion of NSAID users receiving co-therapy and strategies to improve adherence.
Arthritis patients > or =50 years of age received etoricoxib or diclofenac in a double-blind randomized trial. Reminders that high-risk patients (age > or = 65; previous ulcer/haemorrhage; corticosteroid, anticoagulant, aspirin use) should receive co-therapy were given at study initiation. Free PPI was provided. An intervention midway through the study included a written reminder and required written response regarding co-therapy.
16,244/23,504 (69%) patients had GI risk factors. Pre-intervention, co-therapy was most common with previous ulcer/haemorrhage [706/1107 (64%)] and 3-4 risk factors [331/519 (64%)]. In the 10,026 patients enrolled pre-intervention and remaining in the study > or =6 months after, co-therapy in high-risk patients increased from 2958/6843 (43%) to 4177/6843 (61%) (difference = 18%; 95% CI 16%,19%). The increase was greater outside the US (22%; 19%,24%) than in the US (15%; 13%,17%).
Less than 50% of NSAID users with GI risk factors are given protective co-therapy--even if prescribers are given reminders and cost is not an issue. Direct communication requiring written response significantly increased adherence to guidelines, but achieving higher levels of adherence will require additional strategies.
Alimentary Pharmacology & Therapeutics 07/2009; 30(7):767-74. · 3.77 Impact Factor
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ABSTRACT: Lower gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs) are much more poorly characterized than upper gastrointestinal effects.
To determine if NSAIDs increase lower gastrointestinal adverse effects and if the risk with non-selective NSAIDs is greater than with cyclooxygenase-2-selective inhibitors (coxibs).
Computerized databases were searched to identify studies of NSAID use reporting on lower gastrointestinal integrity (e.g. permeability), visualization (e.g. erosions, ulcers) and clinical events.
Designs in 47 studies were randomized (18), case-control (14), cohort (eight) and before-after (seven). Non-selective-NSAIDs had significantly more adverse effects vs. no NSAIDs in 20 of 22 lower gastrointestinal integrity studies, five of seven visualization studies, seven of 11 bleeding studies (OR: 1.9-18.4 in case-control studies), two of two perforation studies (OR: 2.5-8.1) and five of seven diverticular disease studies (OR: 1.5-11.2). Coxibs had significantly less effect vs. non-selective-NSAIDs in three of four integrity studies, one endoscopic study (RR mucosal breaks: 0.3), and two randomized studies (RR lower gastrointestinal clinical events: 0.5; haematochezia: 0.4).
An increase in lower gastrointestinal injury and clinical events with non-selective-NSAIDs appears relatively consistent across the heterogeneous collection of trials. Coxibs are associated with lower rates of lower gastrointestinal injury than non-selective-NSAIDs. More high-quality trials are warranted to more precisely estimate the effects of non-selective-NSAIDs and coxibs on the lower gastrointestinal tract.
Alimentary Pharmacology & Therapeutics 10/2006; 24(5):751-67. · 3.77 Impact Factor
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L Laine
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ABSTRACT: This review examines ulcers and gastrointestinal bleeding with low-dose aspirin, focusing on randomized placebo-controlled trials. The single endoscopic trial assessing ulcers showed no significant difference in 12-week ulcer incidence: 6% of 381 given placebo vs. 7% of 387 given 81 mg enteric-coated aspirin. The relative risk of major gastrointestinal bleeding with low-dose aspirin in a meta-analysis of placebo-controlled trials of vascular protection was 2.07 (95% CI: 1.61-2.66). The absolute rate increase with aspirin above placebo was 0.12% per year (95% CI: 0.07-0.19%) with a number-needed-to-harm of 833 patients (95% CI: 526-1429). A meta-analysis of aspirin 50-1500 mg daily reported an odds ratio for any gastrointestinal bleeding of 1.68 (95% CI: 1.51-1.88) with an number-needed-to-harm at 1 year of 247. The relative risk of hospitalization for upper gastrointestinal bleeding with low-dose aspirin in a large Danish cohort study was 2.6 (95% CI: 2.2-2.9) with an absolute annual incidence of 0.6%. Factors that may increase the risk of gastrointestinal bleeding include prior history of ulcers or gastrointestinal bleeding, corticosteroid use, anticoagulant therapy and addition of a non-aspirin non-steroidal anti-inflammatory drug. When determining whether low-dose aspirin is appropriate for an individual patient, the cardiovascular benefit must be weighed against the potential for clinical events such as gastrointestinal bleeding.
Alimentary Pharmacology & Therapeutics 10/2006; 24(6):897-908. · 3.77 Impact Factor
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ABSTRACT: Treatment with a continuous i.v. proton pump inhibitor is presumed to promote clot formation and stability by sustaining intragastric pH > or = 6.
We postulated that very frequent oral dosing of proton pump inhibitors should simulate i.v. infusion and achieve similar pH control.
Twenty healthy volunteers were stratified by Helicobacter pylori status (10 positive; 10 negative) and had determination of CYP2C19 status. After an overnight fast, an intragastric pH probe was placed. Subjects received 120 mg of lansoprazole at 8 am and 30 mg every 3 h until 8 pm. Intragastric pH was measured over 24 h, and lansoprazole plasma concentrations were determined at five time points.
Intragastric pH was > or = 6 for 41% (95% CI: 30-53%) of the 15-h period from 8 am-11 pm and 46% (95% CI: 35-56%) of the 24-h period (8-8 am). The mean proportion of patients with pH > or = 6 was not significantly different in H. pylori-positive vs. negative patients. Only 25% of subjects sustained pH > or = 6 for at least 60% of the 15-h period, and 35% had a sustained pH > or = 6 for at least 60% of the 24-h period.
A dose of 120 mg of oral lansoprazole followed by standard 30 mg doses of lansoprazole every 3 h did not reliably sustain pH at the desired level of 6.
Alimentary Pharmacology & Therapeutics 07/2006; 23(11):1607-13. · 3.77 Impact Factor
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ABSTRACT: To rationalize decision making around the use of different non-steroidal anti-inflammatory drug (NSAID) treatment strategies in patients with varying degrees of gastrointestinal and cardiovascular risk.
The panel comprised nine physicians (three rheumatologists, two internists, two gastroenterologists and two cardiologists) from geographically diverse areas practising in community-based settings (n = 4) and academic institutions (n = 5). A literature review was performed by the authors on the risks, benefits and costs of NSAIDs, cyclo-oxygenase-2-specific inhibitors and proton pump inhibitor co-therapy. The RAND/UCLA Appropriateness Method was used to rate 304 clinical scenarios as 'appropriate', 'uncertain' or 'inappropriate'.
In patients with no previous gastrointestinal event and not concurrently on aspirin (low risk), the panel rated the use of an NSAID alone as 'appropriate' for those aged < 65 years, and the use of an NSAID +proton pump inhibitor or cyclo-oxygenase-2-specific inhibitor + proton pump inhibitor as 'inappropriate'. For patients aged > 65 years and at low risk, an NSAID or cyclo-oxygenase-2-specific inhibitor alone was rated as 'uncertain'. For patients with a previous gastrointestinal event or who concurrently received aspirin, an NSAID alone was rated as 'inappropriate', and either a cyclo-oxygenase-2-specific inhibitor or an NSAID +proton pump inhibitor was rated as 'appropriate'. Finally, for patients with a previous gastrointestinal event and on aspirin, an NSAID or cyclo-oxygenase-2-specific inhibitor in conjunction with a proton pump inhibitor was rated as 'appropriate'.
Clinicians and managed care entities need to balance the risks, benefits and costs of NSAIDs, cyclo-oxygenase-2-specific inhibitors and the prophylactic use of proton pump inhibitors. The guidelines given here can assist this process.
Alimentary Pharmacology & Therapeutics 01/2004; 19(2):197-208. · 3.77 Impact Factor
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ABSTRACT: Previous studies in patients with osteoarthritis have suggested that the selective cyclooxygenase (COX)-2 inhibitor rofecoxib results in less gastrointestinal damage than non-selective non-steroidal antiinflammatory drugs (NSAIDs). This study compared the incidence of endoscopically detected gastroduodenal ulcers in rheumatoid arthritis patients treated with rofecoxib or a non-selective NSAID.
In this multicentre, randomised, double blind, 12 week study, patients with rheumatoid arthritis were allocated to rofecoxib 50 mg once daily (n=219), naproxen 500 mg twice daily (n=220), or placebo (n=221). Endoscopy was performed at baseline and at six and 12 weeks. Lifetable analysis and log rank tests were used to analyse the incidence of gastroduodenal ulcers > or =3 mm. Gastric or duodenal ulcers > or =5 mm and erosions were also evaluated as secondary end points. Tolerability was assessed by adverse events.
The cumulative incidence of ulcers > or =3 mm at 12 weeks was significantly higher in patients on naproxen (25.5%) than in patients receiving rofecoxib (6.8%; difference 18.7% (95% confidence interval (CI) 11.7%, 25.7%); p<0.001) or placebo (2.9%; difference 22.6% (95% CI 16.1%, 29.1%); p<0.001). The difference between rofecoxib (6.8%) and placebo (2.9%) did not reach statistical significance (p=0.066). Results were similar for ulcers > or =5 mm and for mean changes from baseline in the number of gastroduodenal erosions. The overall incidence of clinical adverse events was similar among treatment groups (61% of patients on placebo, 62% in patients on rofecoxib, and 66% in patients on naproxen).
Rofecoxib 50 mg daily (twice the dose recommended for this patient population) resulted in a lower incidence of endoscopically detected gastroduodenal ulcers and erosions than treatment with naproxen 500 mg twice daily.
Gut 06/2003; 52(6):820-6. · 10.11 Impact Factor
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L Laine
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ABSTRACT: Proton pump inhibitor-based triple therapy is the most commonly used treatment for eradication of Helicobacter pylori, with pooled eradication rates of approximately 90%. In the USA, per protocol eradication rates with 10-day proton pump inhibitor-based triple therapy are approximately 85%. Esomeprazole, a new proton pump inhibitor that is the S-isomer of omeprazole and produces a greater inhibition of acid secretion than omeprazole, has recently been evaluated in the treatment of H. pylori. Seven-day twice daily triple therapy with esomeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg provided intention-to-treat eradication rates of 86-90% and per protocol eradication rates of 90-91% in duodenal ulcer patients in Europe and Canada. Ten-day triple therapy with esomeprazole 40 mg q.d.s., amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. achieved intention-to-treat eradication rates of 77-78% and per protocol eradication rates of 84-85% in USA duodenal ulcer patients. Thus, esomeprazole triple therapy with amoxicillin and clarithromycin is effective in the treatment of H. pylori, with eradication rates comparable to previously studied proton pump inhibitor-based triple therapies.
Alimentary Pharmacology & Therapeutics 08/2002; 16 Suppl 4:115-8. · 3.77 Impact Factor
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ABSTRACT: Concern has been raised that Helicobacter pylori therapy may lead to the development of gastro-oesophageal reflux disease. This prospective study was designed to assess reflux-related quality of life and the symptoms of gastro-oesophageal reflux disease in patients undergoing H. pylori therapy.
Patients with a primary complaint of dyspepsia (upper abdominal pain or discomfort) and endoscopic biopsy positive for H. pylori received triple therapy for 2 weeks. A validated reflux-related quality of life questionnaire sensitive to change was given at baseline, 1 month and 6 months after therapy; symptoms were also recorded. A urea breath test was performed 1 month after the end of therapy; patients and investigators were blind to the results.
H. pylori was eradicated in 48 of 61 patients. The mean scores in cured patients for each of the five domains were comparable at baseline and 6 months after therapy: differences were - 0.23 to 0.13 (P > 0.20) on a scale of 1-7. The proportion of cured patients with a large decrease in quality of life (10-17% in the five domains) was similar to the proportion with a large increase (15-21%). Heartburn was present at baseline in 22 cured patients; at 6 months, it persisted in 13 and resolved in nine, whilst nine patients developed new heartburn.
A population of patients presenting with dyspepsia should have no overall increase or decrease in quality of life due to symptomatic gastro-oesophageal reflux disease in the 6 months after H. pylori therapy.
Alimentary Pharmacology & Therapeutics 06/2002; 16(6):1143-8. · 3.77 Impact Factor
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L Laine
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ABSTRACT: Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are the two major causes of peptic ulcers. This article reviews the interaction of H. pylori and NSAIDs on the development of gastric mucosal histological changes, endoscopically confirmed ulcers, and ulcer complications, and assesses whether underlying H. pylori infection potentiates (or mitigates) the development of NSAID-induced ulcer disease. The weight of evidence does not suggest that H. pylori infection potentiates the risk of ulcer formation or ulcer complications in NSAID users. If such an effect occurs, it is likely to be relatively small. Some data even suggest that H. pylori may be protective against NSAID-induced gastric ulcers. Limited data raise the possibility that H. pylori infection, however, may potentiate the effect of low-dose aspirin with respect to ulcer bleeding. Both NSAIDs and H. pylori are independent risk factors for ulcer disease. Therefore, in an individual patient with an ulcer, one cannot be certain which factor is responsible for the ulcer, and both risks should be removed if possible.
Alimentary Pharmacology & Therapeutics 04/2002; 16 Suppl 1:34-9. · 3.77 Impact Factor
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ABSTRACT: Background:Highly selective inhibitors of the inducible cyclooxygenase-2 enzyme (coxibs) have been associated with less gastrotoxicity than nonselective NSAIDs in clinical studies.Aim:To evaluate the influence of risk factors for NSAID-induced gastrotoxicity on endoscopic and clinical ulcers in patients taking rofecoxib or ibuprofen.Methods:We analysed pooled data from two identical double-blind, randomized, 12-week endoscopy studies which compared the gastroduodenal toxicity of placebo (n=371), rofecoxib 25 mg (n=390), rofecoxib 50 mg (n=379), and ibuprofen 2400 mg daily (n=376) in patients with osteoarthritis. The potential risk factors evaluated were: age (< 65, ≥ 65 years), sex, race (white, nonwhite), Helicobacter pylori status, presence of gastroduodenal erosions at baseline, a history of upper gastrointestinal disease, prior NSAID use within 30 days of study entry, and smoking. We also evaluated these factors for possible association with the development of clinically-evident gastrointestinal perforations, ulcers or bleeds over 12 weeks.Results:Across all treatment groups, the likelihood of detecting endoscopic ulcers, or of clinical presentation with a bleed, over 12 weeks was increased approximately 4–5-fold in patients with previous upper gastrointestinal disease (relative risk [95% confidence interval] of 4.2 [2.5, 7.1] for endoscopic ulcers; 3.8 [1.4, 10.6] for bleeds), or those with gastroduodenal erosions at baseline endoscopy (relative risk of 4.4 [2.6, 7.5] for endoscopic ulcers; 5.0 [1.9, 13.5] for bleeds). H. pylori infection did not increase the risk of endoscopic ulcers or bleeds (relative risk of 1.1 [0.8, 1.6] for endoscopic ulcers; 0.3 [0.1, 0.9] for bleeds). The risk factor sub-group effects were constant across all treatment groups, and the significantly higher incidence of ulcers with ibuprofen as compared to rofecoxib and placebo was maintained in all risk factor subgroups.Conclusions:Gastroduodenal erosions at baseline and a clinical history of upper gastrointestinal disease, but not H. pylori colonization, increased the risk for endoscopically-detected ulcers and clinical bleeds. Rofecoxib did not magnify the risk in any of the patient subgroups studied.
Alimentary Pharmacology & Therapeutics 10/2001; 15(10):1593 - 1601. · 3.77 Impact Factor
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ABSTRACT: Highly selective inhibitors of the inducible cyclooxygenase-2 enzyme (coxibs) have been associated with less gastrotoxicity than nonselective NSAIDs in clinical studies.
To evaluate the influence of risk factors for NSAID-induced gastrotoxicity on endoscopic and clinical ulcers in patients taking rofecoxib or ibuprofen.
We analysed pooled data from two identical double-blind, randomized, 12-week endoscopy studies which compared the gastroduodenal toxicity of placebo (n=371), rofecoxib 25 mg (n=390), rofecoxib 50 mg (n=379), and ibuprofen 2400 mg daily (n=376) in patients with osteoarthritis. The potential risk factors evaluated were: age (< 65, > or = 65 years), sex, race (white, nonwhite), Helicobacter pylori status, presence of gastroduodenal erosions at baseline, a history of upper gastrointestinal disease, prior NSAID use within 30 days of study entry, and smoking. We also evaluated these factors for possible association with the development of clinically-evident gastrointestinal perforations, ulcers or bleeds over 12 weeks.
Across all treatment groups, the likelihood of detecting endoscopic ulcers, or of clinical presentation with a bleed, over 12 weeks was increased approximately 4-5-fold in patients with previous upper gastrointestinal disease (relative risk [95% confidence interval] of 4.2 [2.5, 7.1] for endoscopic ulcers; 3.8 [1.4, 10.6] for bleeds), or those with gastroduodenal erosions at baseline endoscopy (relative risk of 4.4 [2.6, 7.5] for endoscopic ulcers; 5.0 [1.9, 13.5] for bleeds). H. pylori infection did not increase the risk of endoscopic ulcers or bleeds (relative risk of 1.1 [0.8, 1.6] for endoscopic ulcers; 0.3 [0.1, 0.9] for bleeds). The risk factor sub-group effects were constant across all treatment groups, and the significantly higher incidence of ulcers with ibuprofen as compared to rofecoxib and placebo was maintained in all risk factor subgroups.
Gastroduodenal erosions at baseline and a clinical history of upper gastrointestinal disease, but not H. pylori colonization, increased the risk for endoscopically-detected ulcers and clinical bleeds. Rofecoxib did not magnify the risk in any of the patient subgroups studied.
Alimentary Pharmacology & Therapeutics 10/2001; 15(10):1593-601. · 3.77 Impact Factor
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ABSTRACT: To assess the effect of eradication therapy for Helicobacter pylori on symptoms of nonulcer dyspepsia.
Duplicate searches of bibliographic databases, reviews of proceedings of annual gastroenterology and H. pylori meetings from 1995 to 1999, reviews of reference lists, and contact with primary investigators and pharmaceutical manufacturers.
Included studies 1) examined patients with nonulcer dyspepsia and H. pylori infection; 2) used combination therapy for H. pylori and a control therapy without efficacy against H. pylori; 3) were randomized, controlled trials; 4) lasted for at least 1 month after the end of therapy; and 5) assessed symptoms of nonulcer dyspepsia. Ten studies were included.
Independent, duplicate data extraction of the methodologic quality, population, intervention, study design, duration, and outcome of the trials.
The odds ratio (OR) for treatment success in nonulcer dyspepsia with H. pylori eradication therapy compared with control therapy was 1.29 (95% CI, 0.89 to 1.89; P = 0.18). However, significant heterogeneity (P = 0.04) calls the validity of aggregating the data into question. Heterogeneity resolved with the exclusion of one study (OR, 1.07 [CI, 0.83 to 1.37]; P > 0.2). For predefined analysis of trials that used a specifically stated definition of dyspepsia (that is, upper abdominal pain or discomfort), the OR was 1.04 (CI, 0.80 to 1.35) without heterogeneity. For treatment that resulted in cure rather than persistent infection, the OR was 1.17 (CI, 0.87 to 1.59) without heterogeneity.
This meta-analysis provides little support for the use of H. pylori eradication therapy in patients with nonulcer dyspepsia.
Annals of internal medicine 04/2001; 134(5):361-9. · 16.73 Impact Factor
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L Laine
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ABSTRACT: Nonsteroidal anti-inflammatory drugs (NSAIDs) are probably the most common cause of gastroduodenal injury in the United States today. Approximately half of patients who regularly take NSAIDs have gastric erosions, and 15%-30% have ulcers when they are examined endoscopically. However, the incidence of clinical gastrointestinal (GI) events caused by NSAIDs is much lower. Clinical upper GI events may occur in 3%-4.5% of patients taking NSAIDs, and serious complicated events develop in approximately 1.5%. However, the risk varies widely in relationship to clinical features such as history of ulcers or GI events, age, concomitant anticoagulant or steroid use, and NSAID dose. This review discusses the risks of clinical GI disease in NSAID users, the predictors of increased risk, and strategies for prevention of NSAID-associated GI disease.
Gastroenterology 03/2001; 120(3):594-606. · 11.68 Impact Factor
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ABSTRACT: To determine the efficacy of once-daily esomeprazole plus antibiotics for eradication of Helicobacter pylori, to assess the effect of antibiotic resistance on eradication rate, and to define the rate of emergent resistance.
Three separate randomized trials were performed in H. pylori-positive patients with a duodenal ulcer or history of documented duodenal ulcer within 5 yrs: 1) esomeprazole (40 mg once daily), amoxicillin (1 g b.i.d.), and clarithromycin (500 mg b.i.d.; this combination will be referred to as EAC) versus esomeprazole (40 mg once daily) plus clarithromycin (500 mg twice daily; this combination will be referred to as EC); 2) EAC versus esomeprazole (40 mg once daily; E); and 3) EC versus E. Therapy was given for 10 days. Endoscopy and biopsies for CLOtest, histology, and culture with susceptibility testing were done at baseline and 4 wk after completion of therapy.
Per-protocol and intent-to-treat eradication rates, respectively, were as follows. For EAC versus EC in study 1 (N = 448), 84 versus 55% and 77 versus 52% (p < 0.001); for EAC versus E in study 2 (N = 98), 85 versus 5% and 78 versus 4% (p < 0.001); for EC versus E in study 3 (N = 66), 50% versus 0 and 46% versus 0 (p < 0.05). The 15% of patients in the combined studies with baseline clarithromycin resistance had significantly lower rates of eradication than those with susceptible strains (EAC: 45 vs. 89%; EC: 13 vs. 61%). Emergent resistance was less common after treatment with EAC [2/6 (33%)] than with EC (23/27 [85%]).
Ten-day triple therapy with once-daily esomeprazole plus twice-daily amoxicillin and clarithromycin achieves an eradication rate virtually identical to that of the twice-daily proton pump inhibitor-based triple therapies. Baseline clarithromycin resistance, present in 15% of patients, predicts a markedly decreased rate. Use of an amoxicillin-containing regimen may decrease emergence of clarithromycin resistance.
The American Journal of Gastroenterology 12/2000; 95(12):3393-8. · 7.28 Impact Factor
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ABSTRACT: Data on sensitivities of biopsy tests for Helicobacter pylori diagnosis after modern eradication therapy are limited. We assessed diagnostic yield of endoscopic biopsy tests before and after therapy in 2 U.S. multicenter double-blind trials of 10-day proton pump inhibitor-based triple therapy versus dual antibiotic therapy.
Three hundred one patients with duodenal ulcer and H pylori infection had endoscopy at baseline and at 8 weeks. Four antral and 3 body biopsies were taken at both endoscopies: 1 antral biopsy for a rapid urease test (CLOtest), 2 antral and 2 body biopsies for histologic examination (Genta stain), and 1 antral and 1 body biopsy for culture.
The 2 same-site biopsies (antral or body) for histologic examination were in agreement in 97% of cases before treatment and 100% after triple therapy. Histologic examination of antral biopsies without body biopsies missed H pylori infection in 2% of patients before treatment and 5% after triple therapy. Posttreatment sensitivities for triple therapy were significantly lower than pretreatment sensitivities for all tests (e. g., 18% decrease in sensitivity in antral histology, 22% decrease in antral culture); decreases in sensitivity were greater after triple therapy than after the less effective dual therapy. CLOtest plus histology had a post-treatment sensitivity of 96% in the triple therapy group.
A single antral biopsy for histology provides excellent sensitivity for H pylori in untreated patients, but, after effective therapy, sensitivities of biopsy tests decrease. Use of more than one method of testing may increase diagnostic yield when assessing post-treatment H pylori status with endoscopy, whereas the addition of multiple biopsies for each type of test is of more limited value.
Gastrointestinal Endoscopy 07/2000; 51(6):664-9. · 4.88 Impact Factor
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ABSTRACT: This review examines the evidence for the development of adverse effects due to prolonged gastric acid suppression with proton pump inhibitors. Potential areas of concern regarding long-term proton pump inhibitor use have included: carcinoid formation; development of gastric adenocarcinoma (especially in patients with Helicobacter pylori infection); bacterial overgrowth; enteric infections; and malabsorption of fat, minerals, and vitamins. Prolonged proton pump inhibitor use may lead to enterochromaffin-like cell hyperplasia, but has not been demonstrated to increase the risk of carcinoid formation. Long-term proton pump inhibitor treatment has not been documented to hasten the development or the progression of atrophic gastritis to intestinal metaplasia and gastric cancer, although long-term studies are required to allow definitive conclusions. At present, we do not recommend that patients be tested routinely for H. pylori infection when using proton pump inhibitors for prolonged periods. Gastric bacterial overgrowth does increase with acid suppression, but important clinical sequelae, such a higher rate of gastric adenocarcinoma, have not been seen. The risk of enteric infection may increase with acid suppression, although this does not seem to be a common clinical problem with prolonged proton pump inhibitor use. The absorption of fats and minerals does not appear to be significantly impaired with chronic acid suppression. However, vitamin B12 concentration may be decreased when gastric acid is markedly suppressed for prolonged periods (e.g. Zolllinger-Ellison syndrome), and vitamin B12 levels should probably be assessed in patients taking high-dose proton pump inhibitors for many years. Thus, current evidence suggests that prolonged gastric acid suppression with proton pump inhibitors rarely, if ever, produces adverse events. Nevertheless, continued follow-up of patients taking proton pump inhibitors for extended periods will provide greater experience regarding the potential gastrointestinal adverse effects of long-term acid suppression.
Alimentary Pharmacology & Therapeutics 07/2000; 14(6):651-68. · 3.77 Impact Factor
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ABSTRACT: To develop practical guidelines for the treatment of patients with suspected and documented Helicobacter pylori-related gastroduodenal diseases.
A panel of physicians with expertise in H. pylori reviewed, critically appraised, and synthesized the literature on assigned topics and presented their overviews to the panel. Consensus was obtained in controversial areas through discussion.
The panel recommended testing for H. pylori in patients with active ulcers, a history of ulcers, or gastric mucosa-associated lymphoid tissue lymphomas. Young, otherwise healthy patients with ulcerlike dyspepsia and those with a family history or fear of gastric cancer may also undergo H pylori testing. Non-endoscopic methods are preferred for H. pylori diagnosis. Dual medication regimens should not be used for therapy; twice-daily triple therapy with a proton pump inhibitor or ranitidine bismuth citrate, clarithromycin, and amoxicillin for 10 to 14 days is an appropriate therapy. Posttreatment assessment of H. pylori status using urea breath testing should be considered in patients with a documented history of ulcer disease or with persistent symptoms.
Archives of Internal Medicine 06/2000; 160(9):1285-91. · 11.46 Impact Factor
