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.

Prospective study of the frequency and size distribution of polyps missed by colonoscopy.

An important determinant in interpreting the results of colorectal polyp chemoprevention trials is the rate of polyps missed during colonscopic examination. We prospectively examined 90 patients by tandem colonoscopy performed by two alternating examiners. In 69 (76.7%) patients, 221 neoplastic lesions were documented histologically. Of a total of 58 lesions detected in 31 patients, no neoplastic lesion greater than or equal to 10 mm in size was missed; 16% of diminutive (less than or equal to 5 mm) neoplastic polyps and 12.3% of medium-sized (6-9 mm) neoplastic polyps were missed by the first examiner. We conclude that an experienced colonoscopist will miss about 15% of colorectal neoplastic polyps less than 10 mm in size in the setting of adequate bowel preparation. Large (greater than or equal to 10 mm) polyps were rarely missed, however, with the "miss" rate in our study equal to 0, with a 95% confidence limit of 4.64%.

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.

Helicobacter pylori.

Helicobacter pylori is the cause of chronic active gastritis. It is integral to the pathogenesis of peptic ulcer disease and is epidemiologically linked to gastric cancer and lymphoma. Helicobacter pylori can be detected through a variety of invasive (urease testing, culture, or histologic diagnosis of endoscopic biopsies) and noninvasive (urease breath tests, serologic tests) diagnostic tests. It is now appropriate to detect and eradicate H pylori in patients with a peptic ulcer as the natural history of peptic ulcer disease is then markedly improved. At this time, there is no role for H pylori eradication in the prevention of gastric cancer; however, this concept is being actively investigated. There is no indication to treat patients who have H pylori and nonulcer dyspepsia or gastritis because eradication does not reliably affect their symptoms. Current regimens for eradication include bismuth, antibiotics, and antisecretory agents. Complex and poorly tolerated regimens (triple therapy) may no longer be necessary, as simpler regimens (omeprazole and amoxicillin or clarithromycin) appear to be as effective and better tolerated.

Effectiveness of Helicobacter pylori therapies in a clinical practice setting.

BACKGROUND: Whether eradication rates for Helicobacter pylori treatment regimens obtained in controlled clinical trials (efficacy) can also be obtained in clinical practice (effectiveness) is unknown because no such trials have been reported in the United States. OBJECTIVES: To determine the eradication rates of H pylori in a community practice setting and the effects of practice variation in the choice of treatment regimen on patient outcome (H pylori infection cure) and cost. METHODS: Between February 1 and December 30, 1996, 38 community-based gastroenterologists in the Portland, Ore, metropolitan area enrolled a total of 250 patients infected with H pylori, as determined by endoscopic or noninvasive methods. Various therapeutic regimens aimed at eradicating H pylori were used by the gastroenterologists, and a posttreatment urea breath test was used to determine H pylori infection cure. Compliance and incidental effects were also measured and decision analysis was used to estimate the cost of treatment. RESULTS: The regimens used varied considerably. Patients receiving a 2- or 3-times-a-day treatment regimen were significantly more compliant (P=.01) than those receiving a 4-times-a-day regimen. Proton pump inhibitor-based triple-therapy regimens were significantly more effective than all other treatment regimens combined (87% vs 70%; P = .001) in eradicating H pylori. These proton pump inhibitor-based triple-therapy regimens were also more cost-effective by decision analysis for a hypothetical cohort of patients with duodenal ulcer disease. CONCLUSIONS: The considerable variation in the choice of treatment regimens affects the clinical and economic outcomes of patients undergoing therapy for H pylori infection. Whether these data reflect the outcome in other communities is unknown but should be determined. It will be necessary to determine if the dissemination of these data results in a reduction of practice variation and improvement in clinical and economic outcomes of patients being treated for H pylori infection in clinical practice.

A comparison of 10 and 14 days of lansoprazole triple therapy for eradication of Helicobacter pylori.

BACKGROUND: Data from large, multicenter, US studies determining the efficacy of triple therapy for the eradication of Helicobacter pylori are lacking, especially for a treatment duration of less than 14 days. METHODS: Patients with H pylori infection and active duodenal ulcer disease or a history of duodenal ulcer disease within the past year were randomized to receive 30 mg of lansoprazole, 1 g of amoxicillin, and 500 mg of clarithromycin twice daily for 10 or 14 days. The primary efficacy end point was the eradication of H pylori as confirmed by negative histological and culture results at 4 to 6 weeks after the completion of treatment. RESULTS: Of 284 patients enrolled in the study from 46 US sites, 236 met the entry criteria. At 4 to 6 weeks after the end of therapy, H pylori was eradicated in 85% (96/ 113) of the patients receiving 14-day triple therapy and in 84% (103/123) of those receiving 10-day triple therapy by per-protocol analysis (95% confidence interval for treatment group differences, -10.5 to 8.1; P>.05). There was also no significant difference between the 14- and 10-day treatment groups when analyzed by an intent-to-treat analysis of H pylori eradication. A similar proportion of patients in each treatment group reported an adverse event related to therapy (34% [46/136] vs 38% [56/148], respectively). CONCLUSIONS: In patients with an active or a recent history of duodenal ulcer, lansoprazole-based triple therapy for 10 or 14 days is highly effective in the eradication of H pylori. The duration of therapy may be reduced from 14 to 10 days without a significant effect on regimen efficacy.

The diagnosis and treatment of gastroesophageal reflux disease in a managed care environment, Suggested disease management guidelines.

A group of experts from gastroenterology, internal medicine, health economics, medical outcomes, and managed care met in San Francisco, Calif, on September 27, 1994, in an effort to develop clinically and economically effective disease management guidelines to assist physicians in their treatment of gastroesophageal reflux disease in a managed care environment. This article represents a consensus opinion based on the evidence and expert interpretation at the time of that meeting.

Clinical and economic assessment of the omeprazole test in patients with symptoms suggestive of gastroesophageal reflux disease.

OBJECTIVE: To evaluate the diagnostic accuracy of a trial of a high-dose proton pump inhibitor (the omeprazole test) in detecting gastroesophageal reflux disease (GERD) in patients with heartburn symptoms. DESIGN: A randomized, double-blind, placebo-controlled, crossover trial. PATIENTS AND SETTING: Forty-three consecutive patients with symptoms suggestive of GERD were enrolled at a Veterans Affairs medical center. MAIN OUTCOME MEASURES: Symptom response to the omeprazole test vs placebo in GERD-positive and GERD-negative patients; sensitivity, specificity, and positive and negative predictive values of the omeprazole test; and cost per correct diagnosis achieved with the omeprazole test compared with traditional diagnostic strategies. RESULTS: Of 42 patients (98%) who completed the study, 35 (83%) were classified as GERD positive and 7 (17%) as GERD negative. Twenty-eight GERD-positive and 3 GERD-negative patients responded to the omeprazole test, providing a sensitivity of 80.0% (95% confidence interval, 66.7%-93.3%) and a specificity of 57.1% (95% confidence interval, 20.5%-93.8%). Economic analysis revealed that the omeprazole test saves $348 per average patient evaluated, and results in a 64% reduction in the number of upper endoscopies performed and a 53% reduction in the use of pH testing. CONCLUSIONS: The omeprazole test is sensitive and fairly specific for diagnosing GERD in patients with typical GERD symptoms. This strategy could result in significant cost savings and decreased use of invasive diagnostic tests.

Chemopreventive studies in Barrett's esophagus: a model premalignant lesion for esophageal adenocarcinoma.

Barrett's esophagus is a premalignant lesion in which the lower esophagus is lined with metaplastic columnar epithelium rather than the normal stratified squamous epithelium. It is a precursor lesion for adenocarcinoma of the esophagus. We are studying Barrett's esophagus as a model premalignant lesion for adenocarcinoma from the standpoint of identifying biologic markers of increased cancer risk as well as therapeutic strategies for eradicating the lesion. Ornithine decarboxylase (ODC) activity in Barrett's mucosa was significantly higher than in normal adjacent mucosa from the same patient. However, polyamine content was not significantly altered, suggesting dysregulation of the polyamine pathway. Flow cytometry is being used to assess the presence of aneuploidy and its significance in a premalignant lesion. Initial results have demonstrated that aneuploidy and dysplasia can be discordant. Cytogenetic analysis using short-term epithelial cultures established from endoscopic biopsies of the lesion has demonstrated the presence of clonal karyotypic abnormalities. The clinical significance of aneuploidy and abnormal karyotype, however, remains to be proved. Chemopreventive intervention trials have included use of 13-cis-retinoic acid. Considerable toxicity was encountered, and the lesion showed no change in extent in 11 evaluable patients. A subsequent clinical trial with a biologic endpoint used alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, to test whether a low dose could produce changes in polyamine content in gastrointestinal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Ornithine decarboxylase and polyamines in colorectal neoplasia and mucosa.

Ornithine decarboxylase (ODC) and polyamines are intimately involved in normal cellular proliferation and are likely to play a role in carcinogenesis. ODC activity and polyamine content were measured in tissue samples obtained during colonoscopy from 48 benign neoplastic polyps (20 tubular adenomas; 28 villous adenomas), 18 cancers (including 5 malignant polyps), and adjacent mucosa. ODC activity in polyp and cancer tissue specimens was higher than in adjacent mucosa in 75 and 83% of pairs, respectively. Similarly, putrescine, spermidine, and spermine contents were higher in the majority of polyps and cancers compared to adjacent mucosa. ODC activity and polyamine content in colonic mucosa from 10 patients without a history of colorectal neoplasia were not different from adjacent mucosal values in the patients with neoplasia. In conclusion, ODC and polyamines are elevated in the majority of colorectal neoplasms, but amounts in normal mucosa do not differentiate between patients with cancer, benign neoplastic polyps, and normal subjects.

Gastric intestinal metaplasia in ethnic groups in the southwestern United States.

The incidence of gastric cancer has declined dramatically in the United States during this century. However, the incidence of gastric cancer among Hispanics, Blacks, and Native Americans remains 2-3-fold higher than among Whites in this country. Populations with an increased risk of gastric cancer have predominantly the "intestinal" type of gastric cancer, and intestinal metaplasia is regarded as a histological precursor lesion of this type of gastric cancer. We sought to establish the prevalence of intestinal metaplasia, identify associated epidemiological factors, and improve detection of this lesion in a patient population undergoing clinically indicated endoscopy in the Southwestern United States. Among the 440 patients studied, we observed an overall crude prevalence of intestinal metaplasia of 19%. However, the crude prevalence among Hispanics and Blacks was found to be markedly higher than among non-Hispanic Whites (50% versus 13%). Two biopsy protocols (two biopsies versus four biopsies) were used during this study, with a significantly higher rate of intestinal metaplasia detection under the four-biopsy protocol. Adjusting for protocol, we found that age and ethnicity were significantly and independently associated with the prevalence of intestinal metaplasia. The odds of intestinal metaplasia diagnosis was significantly higher in Hispanics compared to non-Hispanic Whites (P < 0.001), and the prevalence of intestinal metaplasia increased with advancing age (P = 0.01). The presence of Helicobacter pylori was also significantly associated with the presence of intestinal metaplasia (P = 0.02), although the direction of the association differed between Hispanics and non-Hispanic Whites.

The cost-effectiveness of the omeprazole test in patients with noncardiac chest pain.

PURPOSE: Recent evidence suggests that an empiric trial of omeprazole (the "omeprazole test") is sensitive and specific for diagnosing gastroesophageal reflux disease (GERD) as the cause of noncardiac chest pain. Our objective was to examine the clinical, economic, and policy implications of alternative diagnostic strategies for patients with noncardiac chest pain. METHODS: Decision analysis was used to evaluate the clinical and economic outcomes of two diagnostic strategies that begin with the omeprazole test (60 mg daily for 7 days) followed sequentially by invasive testing utilizing endoscopy, ambulatory 24-hour esophageal pH monitoring, and esophageal manometry as necessary, compared with two traditional strategies involving sequential invasive diagnostic tests. Cost estimates were based on Medicare reimbursement and the Red Book of average wholesale drug prices. Probability estimates were derived from a systematic review of the medical literature. RESULTS: The average cost per patient for the four diagnostic strategies varied from $1,859 to $2,313. Strategies utilizing the initial omeprazole test resulted in 84% of patients being symptom free at 1 year, compared with 73% to 74% for the strategies that began with invasive tests. The strategy of the omeprazole test, followed if necessary by ambulatory pH monitoring, then manometry, and then endoscopy, was both most effective and least expensive. It led to an 11% improvement in diagnostic accuracy and a 43% reduction in the use of invasive diagnostic tests, thus yielding an average cost savings of $454 per patient, compared with the strategy of beginning with endoscopy, then pH monitoring, and then manometry. CONCLUSIONS: Among patients with noncardiac chest pain, diagnostic strategies that begin with the omeprazole test result in reduced costs, improved diagnostic certainty, and a greater proportion of symptom-free patients at 1 year than do traditional strategies that begin with invasive diagnostic tests.

Symptom status and the desire for Helicobacter pylori confirmatory testing after eradication therapy in patients with peptic ulcer disease.

BACKGROUND: There is consensus that individuals with Helicobacter pylori-associated peptic ulcer disease should receive a test to confirm H. pylori cure if symptoms recur after eradication therapy. It remains controversial whether individuals who are asymptomatic after therapy should undergo a confirmatory test to establish cure. Patients' desire to know whether their infection has been cured and symptom status after treatment are two important determinants of whether confirmatory H. pylori testing should be undertaken routinely. METHODS: We identified 87 patients with H. pylori-associated peptic ulcer disease scheduled to undergo urea breath testing 4 weeks after H. pylori eradication therapy. At the time of testing, willingness-to-pay methodology was used to estimate patients' desire for confirmatory testing in the absence of symptoms. At a follow-up visit after eradication therapy (mean follow-up, 297 days; range, 143 to 494 days), patients were surveyed to assess gastrointestinal symptom status. RESULTS: Of the 87 patients, 78 (90%) responded that they would prefer to undergo confirmatory testing if asymptomatic, as opposed to delaying testing until symptoms recurred. Patients' median willingness to pay for confirmatory testing in the absence of symptoms was greater than $50. On follow-up, 38% of patients in whom H. pylori was eradicated reported that their symptoms were completely resolved. There was no significant difference in the percentage of patients who reported complete symptom resolution by H. pylori status (H. pylori eradicated 38%, H. pylori infected 28%, P = 0.42, 95% confidence interval, -14% to 34%). CONCLUSIONS: Patients' desire for confirmation of cure, coupled with a frequent need for confirmatory testing as a result of recurrent symptoms after therapy, may justify routine confirmatory testing after H. pylori treatment.

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.

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.

Review article: Barrett's oesophagus--cancer risk, biology and therapeutic management.

Barrett's oesophagus is receiving increasing scrutiny as the rates of adenocarcinoma of the oesophagus rise. Because clinical features are not predictive of the presence of Barrett's oesophagus and most individuals with Barrett's oesophagus go undetected, a case can be made for surveillance endoscopy in patients with chronic reflux. Once Barrett's oesophagus is diagnosed patients should be entered into a surveillance programme despite lack of proof of efficacy. Scientific study of putative biological markers of increased risk has added dramatically to the understanding of the biology of the lesion, but currently the finding of high grade dysplasia remains the best marker predicting the presence of greatly increased risk of developing cancer. It is likely that newer molecular biology techniques will become clinically applicable biological markers in the future. Currently there is no effective medical nor surgical therapy to cause regression of the metaplastic Barrett's epithelium, however the application of novel de-differentiating agents or ablation of the metaplastic epithelium while controlling oesophageal acid exposure and other environmental abnormalities offer hope that effective treatment of Barrett's oesophagus may someday be reality.

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.