Systematic review: the role of bile acids in the pathogenesis of gastro-oesophageal reflux disease and related neoplasia.

BACKGROUND: Factors other than acid may play a role in gastro-oesophageal reflux disease (GERD) and its complications. AIM: To assessed the role of bile acids in the pathogenesis of GERD, Barrett's oesophagus and Barrett's-related neoplasia. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Randomised clinical trial: MiraLAX vs. Golytely - a controlled study of efficacy and patient tolerability in bowel preparation for colonoscopy.

BACKGROUND: MiraLAX is gaining acceptance as a bowel cleanser for colonoscopy. We hypothesize that MiraLAX/Gatorade is as efficacious for bowel cleansing as Golytely and is more tolerable for patients undergoing screening colonoscopy. AIM: To compare bowel preparation scores of MiraLAX/Gatorade vs. Golytely and examine differences in patient tolerability. METHODS: Patients undergoing screening colonoscopy were randomized to 4 L Golytely or 238 g MiraLAX in 64 ounces Golytely and four bisacodyl tablets. Efficacy in bowel cleansing was assessed using the Boston Bowel Preparation Scale (BPPS). Subjects completed a brief survey assessing patient tolerability. RESULTS: A total of 190 patients were enrolled (85 male, 105 female; mean age 56.9 years, s.d. 6.3); 87 were randomized to MiraLAX, 103 to Golytely. There was no difference in age, gender or timing of colonoscopy between the bowel preparation groups. Golytely's median total BBPS score was significantly higher than that of MiraLAX [9 (IQR 7-9) vs. 8 (IQR 6-9), P = 0.034]. Golytely had a higher rate of an excellent equivalent BBPS score of 8 or 9 than MiraLAX (70% vs. 55%, P = 0.036). There was no difference in patient tolerability (P = 0.857). CONCLUSIONS: Golytely was more efficacious than MiraLAX/Gatorade in bowel cleansing; both preparations were equally tolerated by patients.

Clinical trial: lansoprazole 15 or 30 mg once daily vs. placebo for treatment of frequent nighttime heartburn in self-treating subjects.

BACKGROUND: Frequent nighttime heartburn is common. Lansoprazole 15 mg is indicated for treatment of heartburn and other gastro-oesophageal reflux disease-related symptoms. AIM: To evaluate the efficacy and safety of lansoprazole in self-treating subjects with frequent nocturnal heartburn. METHODS: A total of 864 subjects with heartburn on >or=2 days/week over the past month were randomized to double-blind treatment with lansoprazole 15 or 30 mg or placebo each morning. Endpoints were percentage of night times without heartburn (primary), percentage of 24-h days without heartburn and percentage of subjects without heartburn on day 1. RESULTS: Mean percentage of night times without heartburn was significantly greater with lansoprazole 15 mg (61.3%) or lansoprazole 30 mg (61.7%) vs. placebo (47.8%) over 14 days (P < 0.0001 vs. placebo for both doses). Percentage of 24-h days without heartburn and percentage of subjects without heartburn on day 1 were significantly greater with lansoprazole 15 or 30 mg vs. placebo. CONCLUSIONS: Both lansoprazole 15 and 30 mg were highly effective and well tolerated in reducing symptoms in subjects with frequent nighttime heartburn. The benefit of therapy on 24-h heartburn and nighttime heartburn on day 1 of treatment was also evident. Lansoprazole 15 mg is a suitable choice for management of frequent nighttime heartburn.

Decreasing prevalence combined with increasing eradication of Helicobacter pylori infection in the United States has not resulted in fewer hospital admissions for peptic ulcer disease-related complications.

BACKGROUND: Helicobacter pylori infection is a major cause of peptic ulcer disease, but the prevalence of this infection has been decreasing steadily. Additionally, eradication of H. pylori decreases ulcer recurrence and prevents ulcer complications such as bleeding. AIM: To examine whether the decreased prevalence of H. pylori and increased use of eradication regimens have affected the prevalence of peptic ulcer disease-related hospitalizations. METHODS: We chose to study a period between 1996 and 2005. The number of gastric and duodenal ulcers as primary or secondary hospital discharge diagnoses per year for the 10-year span was collected from five large US hospitals. Collected data were analysed using Spearman correlation. RESULTS: No statistically significant trend was observed in the number of gastric or duodenal ulcers listed as primary or secondary discharge diagnoses at any of the five healthcare centres. CONCLUSIONS: Despite a decreasing prevalence of H. pylori and the increasing use of successful H. pylori eradication regimens, the prevalence of peptic ulcer disease and its complications has not changed. In the US other aetiologies, including non-steroidal anti-inflammatory drugs, may be playing a larger role than once thought.

Review article: alternative approaches to the long-term management of GERD.

Although proton-pump inhibitors are highly effective for the treatment of gastro-oesophageal reflux disease, there are issues with long-term maintenance therapy: not all patients require full daily dose for maintenance treatment, some patients are reluctant to take long-term daily medication, and long-term PPI therapy is inadequate for some patients. This article aims to review alternatives to daily proton-pump inhibitor therapy for the long-term management of gastro-oesophageal reflux disease, including intermittent or on-demand proton-pump inhibitor use, as well as endoscopic and surgical options. On-demand proton-pump inhibitor therapy has demonstrated efficacy in achieving acceptable symptom control, healing and maintenance of quality of life for a proportion of patients with gastro-oesophageal reflux disease. Endoscopic antireflux procedures can reduce the need for proton-pump inhibitor therapy, but safety and durability of these procedures require more study. Surgical treatment of gastro-oesophageal reflux disease in properly selected patients has demonstrated efficacy in reducing symptoms and the need for proton-pump inhibitor therapy; however, long-term follow-up suggests that it is not a permanent solution for many patients. While daily proton-pump inhibitor therapy remains the main treatment regimen option for most patients with gastro-oesophageal reflux disease, on-demand therapy may prove effective for many patients. Endoscopic anti-reflux therapies and surgery are options for patients who prefer nonpharmacological treatment, but experience is limited at this point in time for the former.

Efficacy of esomeprazole 40 mg vs. lansoprazole 30 mg for healing moderate to severe erosive oesophagitis.

BACKGROUND: Secondary analyses from previous studies indicated that esomeprazole was more effective than lansoprazole and omeprazole in healing moderate or severe (Los Angeles grades C or D) erosive oesophagitis (EE). AIM: To compare prospectively healing rates with esomeprazole vs. lansoprazole in patients with moderate to severe EE. METHODS: In this multicentre, randomized, double-blind, parallel-group trial, adult patients with endoscopically confirmed moderate or severe EE received esomeprazole 40 mg (n = 498) or lansoprazole 30 mg (n = 501) once daily for up to 8 weeks. The primary end point was EE healing through week 8. Secondary assessments included investigator-assessed resolution of symptoms and safety and tolerability. RESULTS: Time to healing was significantly different (P = 0.007), favouring esomeprazole. Estimated healing rates at week 8 were 82.4% with esomeprazole 40 mg and 77.5% with lansoprazole 30 mg. Heartburn resolved at week 4 in 72% and 64% of patients who received esomeprazole and lansoprazole, respectively (P = 0.005). Control of other GERD symptoms was similar between treatments. Both treatments were well tolerated. CONCLUSIONS: With 8 weeks' treatment, esomeprazole 40 mg once daily heals moderate to severe EE faster and in more patients, and resolves heartburn in more patients after 4 weeks of treatment, than lansoprazole 30 mg once daily.

Systematic review: Is there excessive use of proton pump inhibitors in gastro-oesophageal reflux disease?

BACKGROUND: Proton-pump inhibitors are often recommended for continuous use in gastro-oesophageal reflux disease, but this may not be necessary in all patients. AIM: To ascertain the level of evidence for alternative strategies for proton-pump inhibitor treatment in gastro-oesophageal reflux disease. METHODS: We searched for observational or interventional studies examining alternatives to continuous proton-pump inhibitor treatment in gastro-oesophageal reflux disease. RESULTS: Non-randomized studies suggest that some patients with gastro-oesophageal reflux disease, including some with erosive oesophagitis, may be adequately maintained on proton-pump inhibitor therapy given less frequently than once daily. However, the results may not be generalizable. Four high quality randomized-controlled trials compared 'on-demand' proton-pump inhibitor and placebo treatment in endoscopy-negative reflux disease; all found this effective for most patients. One high quality randomized-controlled trial found intermittent courses of a proton-pump inhibitor or H2-receptor antagonist in erosive oesophagitis or endoscopy-negative reflux disease adequate for almost half of the patients studied. Up to 80% of patients on continuous high-dose proton-pump inhibitor treatment for gastro-oesophageal reflux disease can be 'stepped down' to less intensive therapy. CONCLUSIONS: On-demand proton-pump inhibitor treatment may be appropriate in endoscopy-negative reflux disease. In gastro-oesophageal reflux disease, patients taking more than once daily or high-dose proton-pump inhibitor treatment, a step down to once daily or standard dose therapy should be attempted.

Assessment of oesophageal motor function in patients with dysphagia or chest pain - the Clinical Outcomes Research Initiative experience.

BACKGROUND: Available prospectively acquired data on the distribution of oesophageal motor abnormalities in patients being evaluated for non-cardiac chest pain and/or dysphagia are relatively scarce. AIM: To evaluate the distribution of oesophageal motor abnormalities in patients with dysphagia, non-cardiac chest pain or both using the national Clinical Outcomes Research Initiative (CORI) database. METHODS: The CORI oesophageal motility database originates from 19 community, university and VA medical centres. Data were collected using a computerized motility report-generating program, combined with the CORI module. Data from each site were encrypted and sent to the CORI National Repository for analysis. The database includes the assessment of the lower and upper oesophageal sphincter function and the motor activity of the oesophageal body. RESULTS: Five hundred and eighty-seven consecutive patients who underwent motility studies between 1998 and 2001 were included in the CORI database and analysed for this report. Four hundred and three patients (69%) had dysphagia as their primary indicator for the examination, 140 patients (24%) had non-cardiac chest pain and 44 patients (7%) had both dysphagia and non-cardiac chest pain. In all three groups, a normal motility study was the most frequent finding (dysphagia, 53%; chest pain, 70%; both, 55%). The most common motility abnormality in the group with non-cardiac chest pain was a hypotensive lower oesophageal sphincter (61%). Nutcracker oesophagus and non-specific oesophageal motility disorders were each diagnosed in only 10% of patients with non-cardiac chest pain. In patients with dysphagia, ineffective peristalsis was the most common oesophageal dysmotility (27%), followed by achalasia and non-specific oesophageal motility disorders (18% and 14%, respectively). Achalasia and non-specific oesophageal motility disorders were the most common oesophageal motility abnormalities in patients with both chest pain and dysphagia (35% and 25%, respectively). CONCLUSIONS: The most common oesophageal motility abnormality in patients with non-cardiac chest pain is a hypotensive lower oesophageal sphincter; nutcracker oesophagus and non-specific oesophageal motility disorders are relatively uncommon; the most common oesophageal motility abnormality in patients with dysphagia is ineffective peristalsis and, for those with both dysphagia and non-cardiac chest pain, it is achalasia.

Direct comparative trials of the efficacy of proton pump inhibitors in the management of gastro-oesophageal reflux disease and peptic ulcer disease.

BACKGROUND: Five proton pump inhibitors are now available for use in North America. Claims of differences in the clinical efficacy of different strengths and/or agents have been made. AIM: To identify any consistent evidence of differences in outcomes between agents or doses within this class of drugs. METHODS: A search of the medical literature was performed in two electronic databases, and randomized controlled trials of higher quality were included in the assessment. RESULTS AND CONCLUSIONS: Thirty-two trials met our criteria. No convincing data were found to indicate that low doses of proton pump inhibitors are as effective as standard doses of proton pump inhibitors in the healing of erosive oesophagitis or in the relief of symptoms of gastro-oesophageal reflux disease; however, they may be as effective as maintenance therapy for gastro-oesophageal reflux disease and peptic ulcer disease. Differences were found between the standard doses of proton pump inhibitors with regard to the onset of symptom relief in gastro-oesophageal reflux disease (lansoprazole was faster than omeprazole, and esomeprazole was faster than both lansoprazole and omeprazole) and the healing of oesophagitis (esomeprazole was superior to both omeprazole and lansoprazole). Despite these differences, there are as yet insufficient data to establish the superiority of any one agent over all others across all disease states treated with these agents.

Systematic review: peginterferon vs. standard interferon in the treatment of chronic hepatitis C.

BACKGROUND: Randomized controlled trials over the last decade have demonstrated incremental improvement in the treatment efficacy of chronic hepatitis C with combination interferon and ribavirin therapy when compared with interferon monotherapy. AIM: To perform a systematic review of clinical trials directly comparing interferon formulations to test the hypothesis that a true difference in terms of efficacy exists between standard interferon (with and without ribavirin) and peginterferon (with and without ribavirin). METHODS: A search of the on-line bibliographic databases MEDLINE and PUBMED was performed independently by two authors to identify all relevant articles. In addition, the reference sections of all relevant articles were manually searched to identify any missed articles. Quality was assessed using the Jadad scale, which is an accepted scale specific for randomized controlled trials. A priori, it was decided to include only articles with a Jadad score of three or higher in the final analysis. Data were abstracted on to pre-determined abstraction sheets. The inclusion of articles, the data abstracted and the methodological score differences were adjudicated by consensus with agreement of the authors performing the search. RESULTS: Seven citations of randomized controlled trials, comparing at least two different interferon formulations and evaluating the sustained virological response as a primary end-point, were identified. These relevant articles were abstracted, and five of the seven were found to have a Jadad score of three or higher and comprised the final set of citations reviewed. The studies consistently demonstrated that peginterferon monotherapy was superior to standard interferon, even in patients with advanced fibrosis. With regard to combination interferon therapy, only two high-quality articles compared peginterferon plus ribavirin with standard interferon plus ribavirin. Both studies demonstrated that the overall sustained virological response was statistically better with peginterferon plus ribavirin. CONCLUSIONS: On the basis of this systematic review, peginterferon-based regimens are superior to standard interferon-based regimens for the treatment of chronic hepatitis C.

Systematic review: the economic impact of irritable bowel syndrome.

BACKGROUND: Although little mortality is associated with irritable bowel syndrome, curative therapy does not exist and thus the economic impact of this disorder may be considerable. METHODS: A systematic review of the literature was performed. Studies were included if their focus was irritable bowel syndrome, and direct and/or productivity (indirect) costs were reported. Two investigators abstracted the data independently. RESULTS: One hundred and seventy-four studies were retrieved by the search; 11 fulfilled all criteria for entry into the review. The mean direct costs of irritable bowel syndrome management were reported to be UK pound sterling90, Canadian$259 and US$619 per patient annually, with total annual direct costs related to irritable bowel syndrome of pound sterling45.6 million (UK) and $1.35 billion (USA). Direct resource consumption of all health care for irritable bowel syndrome patients ranged from US$742 to US$3166. Productivity costs ranged from US$335 to US$748, with total annual costs of $205 million estimated in the USA. Annual expenditure for all health care, in addition to expenditure limited to gastrointestinal disorders, was significantly higher in irritable bowel syndrome patients than in control populations. CONCLUSIONS: Despite the lack of significant mortality, irritable bowel syndrome is associated with high direct and productivity costs. Irritable bowel syndrome patients consume more gastrointestinal-related and more total health care resources than non-irritable bowel syndrome controls, and sustain significantly greater productivity losses.

Use of antisecretory agents as a trial of therapy.

Dyspepsia is a common clinical condition, and its diagnostic evaluation and treatment result in the expenditure of enormous healthcare resources each year. Studies indicate that the omeprazole test is the most sensitive and cost effective test for diagnosing gastro-oesophageal reflux disease (GORD) in patients with extra-oesophageal or more "classic" symptoms suggestive of GORD. Studies also indicate that a therapeutic trial of omeprazole in patients with dyspepsia results in greater symptom improvement and lower costs than treatment with less potent acid suppression.

The clinical and economic impact of competing management strategies for gastro-oesophageal reflux disease.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is a common disorder in the primary care setting. Traditional management strategies consist of sequentially intensive therapeutic trials followed by invasive diagnostic testing for nonresponders. A high dose proton pump inhibitor trial (the "proton pump inhibitor test") has been shown to be an accurate diagnostic alternative, and may be an efficient initial approach to patients with GERD symptoms. AIM: To examine the clinical, economic and policy implications of alternative management strategies for GERD. METHODS: Decision analysis was used to calculate the clinical and economic outcomes of competing management strategies. The traditional strategy incorporates sequential therapeutic trials with more intensive therapy ("step-up" approach) followed by sequential invasive diagnostic testing of nonresponders. The "proton pump inhibitor test" strategy includes an initial "proton pump inhibitor test" (7 days of omeprazole; 40 mg AM + 20 mg PM daily) followed by less intensive therapeutic trials in those testing positive ("step-down" approach) with sequential invasive diagnostic testing as needed. Cost estimates were based on Medicare reimbursement and average wholesale drug prices. Probability estimates were derived from a systematic review of the published medical literature. Model results are reported as the average and incremental cost-per-symptom free patient and cost-per-quality-adjusted life-years (QALYs) gained. RESULTS: The average cost per patient was 1045 US dollars for the traditional step-up management strategy, compared to 1172 US dollars for the "proton pump inhibitor test" and step-down strategy. The percentage of patients who were symptom-free at 1 year was 50% for the traditional management strategy compared to 75% for the "proton pump inhibitor test" strategy. The "proton pump inhibitor test" strategy results in QALY gains of 0.01-0.05 depending on the utility estimate employed. The incremental cost-effectiveness ratio for the "proton pump inhibitor test" strategy is 510 US dollars per additional symptomatic cure over 1 year, and between 2822-10,160 US dollars per QALY gained. The traditional management strategy resulted in a greater than 5-fold increase in the utilization of upper endoscopy, which was partially offset by a 47% reduction in the use of ambulatory 24-h oesophageal pH monitoring. The reduced effectiveness of the traditional management strategy may be attributed in part to a 118% increase in the use of "high-dose" H2RAs while reducing the use of standard dose proton pump inhibitors by only 42% and "high-dose" proton pump inhibitors by 57%. CONCLUSIONS: Based on the results of this analysis, strategies utilizing the initial PPI test followed by a "step-down" approach may result in improved symptom relief and quality of life over 1 year, and more appropriate utilization of invasive diagnostic testing at a small marginal increase in total costs. These findings warrant a prospective trial comparing these competing management strategies.

Review article: Helicobacter pylori and uninvestigated dyspepsia.

Although dyspepsia is a very common disorder, the incidence of Helicobacter pylori infection in Western medical clinics is very low (20-35%). In cases where H. pylori is detected, elimination of it may be cost-effective in the long term, but even eradication is not a guarantee for long-term relief. Further studies to determine the connection between H. pylori and dyspepsia need to be completed before H. pylori eradication becomes the treatment of choice for that minority of patients. The majority of dyspeptic patients are not as simple to diagnose, and may need several empirical trials of therapy, or more specific diagnostic assessment.

Risk factors for post-ERCP pancreatitis: a prospective, multicenter study.

BACKGROUND: Post-ERCP pancreatitis is poorly understood. The goal of this study was to comprehensively evaluate potential procedure- and patient-related risk factors for post-ERCP pancreatitis over a wide spectrum of centers. METHODS: Consecutive ERCP procedures were prospectively studied at 11 centers (6 private, 5 university). Complications were assessed at 30 days by using established consensus criteria. RESULTS: Pancreatitis occurred after 131 (6.7%) of 1963 consecutive ERCP procedures (mild 70, moderate 55, severe 6). By univariate analysis, 23 of 32 investigated variables were significant. Multivariate risk factors with adjusted odds ratios (OR) were prior ERCP-induced pancreatitis (OR 5.4), suspected sphincter of Oddi dysfunction (OR 2.6), female gender (OR 2.5), normal serum bilirubin (OR 1.9), absence of chronic pancreatitis (OR 1.9), biliary sphincter balloon dilation (OR 4.5), difficult cannulation (OR 3.4), pancreatic sphincterotomy (OR 3.1), and 1 or more injections of contrast into the pancreatic duct (OR 2.7). Small bile duct diameter, sphincter of Oddi manometry, biliary sphincterotomy, and lower ERCP case volume were not multivariate risk factors for pancreatitis, although endoscopists performing on average more than 2 ERCPs per week had significantly greater success at bile duct cannulation (96.5% versus 91.5%, p = 0.0001). Combinations of patient characteristics including female gender, normal serum bilirubin, recurrent abdominal pain, and previous post-ERCP pancreatitis placed patients at increasingly higher risk of pancreatitis, regardless of whether ERCP was diagnostic, manometric, or therapeutic. CONCLUSIONS: Patient-related factors are as important as procedure-related factors in determining risk for post-ERCP pancreatitis. These data emphasize the importance of careful patient selection as well as choice of technique in the avoidance of post-ERCP pancreatitis.

Outcomes of Helicobacter pylori treatment in community practice and impact of therapeutic effectiveness information on physician behaviour.

BACKGROUND: The effect of knowledge of Helicobacter pylori eradication rates on physician choice of treatment regimen is unknown. As practice variation results in differences in outcome, it is important to determine whether physician behaviour can be altered by such knowledge. AIMS: (i) To determine whether dissemination of practice variation and effectiveness data regarding H. pylori changes subsequent prescribing behaviour and (ii) whether this change results in an improvement in the effectiveness of therapy. METHODS: Community gastroenterologists in the Portland metropolitan area enrolled patients being treated for H. pylori. The regimen used, diagnostic method, indication and success in eradication was measured. Patient-centred factors were also measured, including symptoms, interest in post-treatment diagnostic testing and willingness to pay. RESULTS: Significantly more physicians participating in both studies used proton pump inhibitor-triple therapy based regimens in this trial (46% vs. 85%, P=0.01), although the overall difference between the two trials was not significant (62% vs. 83%, P=0.11). There was no change in overall eradication rates by per protocol analysis between trials (84% vs. 85%, P=0.78), but a significant decrease in effectiveness by intention-to-treat analysis observed in this study (80% vs. 71%, P=0.03). Significantly more patients were treated for reasons other than peptic ulcer disease in this study (P=0.0003). CONCLUSIONS: The overall effectiveness of H. pylori therapy in practice remains good. There has been a shift in the choice of treatment regimen and indication for therapy between the time periods of the two studies. Dissemination of treatment data appears to effect prescribing behaviour, but whether it has a beneficial effect on treatment outcome remains unproven.

A randomized trial of lansoprazole, amoxycillin, and clarithromycin versus lansoprazole, bismuth, metronidazole and tetracycline in the retreatment of patients failing initial Helicobacter pylori therapy.

BACKGROUND/AIM: 10-30% of the patients treated for Helicobacter pylori fail to clear the infection after initial therapy. Little is known as to the efficacy of retreatment regimens in these patients. Proton pump inhibitor (PPI) -based triple and quadruple therapies demonstrate efficacies of 80-90% as initial therapy for H. pylori infection, but whether these regimens are as effective when used for retreatment is unknown. The efficacy of a metronidazole-containing regimen in this situation is also unknown. Our aim was to compare the efficacy of a nonmetronidazole-containing PPI-based triple versus a PPI-based quadruple therapy containing metronidazole in patients failing previous H. pylori therapy. METHODS: 48 patients were enrolled in this study at two sites after failure of previous H. pylori therapy as determined by a positive (14)C-urea breath test. Patients were stratified by prior treatment with a metronidazole-containing regimen and were then randomized to either lansoprazole (L) 30 mg twice daily, amoxycillin (A) 1,000 mg twice daily, and clarithromycin (C) 500 mg twice daily for 14 days (LAC) or L 30 mg four times daily, bismuth subsalicylate (B) 2 tablets four times daily, metronidazole (M) 250 mg four times daily and tetracycline (T) 250 mg four times daily for 14 days (LBMT). Side effects and compliance (pill count) were assessed at the completion of therapy. A repeat (14)C-urea breath test was performed 4 or more weeks after completion of therapy, and cure was defined as a negative test result. RESULTS: 48 patients (16 males and 32 females) were enrolled in this study. 20 patients received LAC (18 prior M), and 28 received LBMT (23 prior M). Per protocol and intention-to-treat efficacies were 82% (95% CI 64-100%) and 75% (95% CI 56-94%) for LAC and 80% (96% CI 64-96%) and 71% (95% CI 54-88%) for LBMT (p = 0.85 per protocol and p = 0.78 intention to treat between LAC and LBMT), respectively. The compliance (> or =80% of pills taken) was found to be 89% in both treatment groups. Side effects were noted in 84% for LAC and in 82% for LBMT, but were mild and did not cause discontinuation of therapy. CONCLUSIONS: PPI-based triple and quadruple therapy with both LAC and LBMT are effective in retreating patients failing initial metronidazole-based H. pylori therapies. LAC was not statistically superior to LBMT as a 'retreatment' regimen in this clinical situation, but the small sample size and wide confidence limits do not preclude the possibility of a smaller but significant difference in efficacy between the regimens. To determine whether LAC or LBMT is as effective for retreating patients failing non-metronidazole-containing regimens requires further study.

NSAID-related gastrointestinal injury. Evidence-based approach to a preventable complication.

NSAID-induced gastrointestinal mucosal injury and its subsequent complications are a tremendously important clinical problem. Effective prophylactic and treatment strategies involve proton pump inhibitors, misoprostol, or selective COX-2 inhibitors. These agents are capable of dramatically decreasing or eliminating the risk of mucosal injury as well as the morbidity and mortality for this disorder. Identification of the at-risk patient and initiation of appropriate preventive therapy are the keys to minimizing the societal burden of this disease process.