Funding source and conflict of interest disclosures by authors and editors in gastroenterology specialty journals revisited.

BACKGROUND: A survey of journals published in the field of Gastroenterology conducted 5 years ago showed marked variability in reporting of conflicts of interest or funding sources in these journals. AIM: To re-examine reporting of conflicts of interest and funding sources for original articles and editorials in Gastroenterology and Hepatology journals. METHODS: We evaluated all original articles and editorials in 15 leading journals (determined by impact factor-Thomson Reuter Science Citation Index) devoted to Gastroenterology and Hepatology for disclosures of conflicts and for editor's self disclosures. We examined each journal's editorial policy by contacting the journal directly if the information was not revealed on the Web site or print versions of the journal. RESULTS: Of the 1574 articles evaluated, a total of 1207 (77%) reported the presence or absence of a potential conflict of interest and 1047 (67%) reported the presence or absence of funding sources. A total of 3 of the 15 (20%) journals (American Journal of Gastroenterology, Gastroenterology, and Alimentary Pharmacology and Therapeutics reported the presence or absence of funding sources in all their published original articles. Only 5 of 15 (33%) journals (Gut, Gastrointestinal Endoscopy, American Journal of Gastroenterology, Neurogastroenterology & Motility and Alimentary Pharmacology and Therapeutics) publicly disclosed the conflicts of interest of the editors. CONCLUSIONS: (i) Funding sources and conflicts of interest are still reported variably in the GI literature. (ii) Editorials and review articles are influential, but have poor reporting of conflicts of interest. (iii) Editors of many journals still do not report their conflicts of interest.

Randomised clinical trial: the burden of illness of uninvestigated dyspepsia before and after treatment with esomeprazole--results from the STARS II study.

BACKGROUND: Patients with dyspepsia often experience troublesome symptoms. AIM: To assess the burden of uninvestigated dyspepsia (symptoms, health-related quality of life [HRQL] and work productivity) before and after 8 weeks' esomeprazole treatment. METHODS: Patients (n=1250) with uninvestigated dyspepsia (no endoscopy within 6 months and ≤ 2 endoscopies within 10 years) underwent a 1-week esomeprazole acid-suppression test before randomisation to 7 weeks' esomeprazole or placebo. The Reflux Disease Questionnaire (RDQ), Quality of Life in Reflux and Dyspepsia (QOLRAD) and Work Productivity and Activity Impairment (WPAI) questionnaires were completed at baseline (1-week off-treatment) and 8 weeks. WPAI results were further analysed among patients who responded to the acid-suppression test. RESULTS: The highest baseline symptom score was for the RDQ dyspepsia domain, and the highest disease burden was for QOLRAD vitality and food/drink problems. After 8 weeks, significant improvements vs. placebo were observed for all RDQ and QOLRAD domains. The sub-population of acid-suppression test responders, but not the total WPAI population, had a significant work productivity improvement vs. placebo. CONCLUSIONS: Uninvestigated dyspepsia is associated with high symptom load and impacts on HRQL and work productivity. Esomeprazole improves HRQL among such patients, and improves work productivity among 1-week acid-suppression trial responders. ClinicalTrials.gov identifier: NCT00251992.

Duplicate breath testing to confirm eradication of Helicobacter pylori: incremental benefit and cost in 419 patients.

BACKGROUND: Current standards for establishing a cure of H. pylori infection require two breath tests taken at least 4 weeks apart, to be negative. AIM: To determine the incremental cost and accuracy of repeating a urea breath test (UBT) in clinical practice. METHODS: We identified 419 patients with documented Helicobacter pylori infection who received eradication therapy and then had two breath tests, one 4 weeks and the second at least 8 weeks after the completion of treatment. H. pylori infection was documented at baseline by a positive rapid urease test and histology. RESULTS: In patients with successful eradication of H. pylori infection (n = 317), the mean +/- standard deviation delta over baseline (DOB) value before treatment was 43 +/- 29 ppm. Following treatment, the mean DOB in cured was 0.56 +/- 2.1 ppm at 1 month and was similar to the value obtained at the second breath (0.68 +/- 1; P = 0.39), which was performed 60 +/- 71 days after the first UBT. In patients remaining infected (n = 102), the mean DOB at baseline was 47 +/- 20 ppm. Four weeks after treatment, the DOB was 40 +/- 32 ppm. The second UBT was performed 94 +/- 72 days after the first and the DOB was significantly greater than the first (47 +/- 28; P = 0.040). There was no discordant result between the first breath test and second breath test. At a cost of 30 euros/breath test, the incremental cost of a second breath test was 12 570 euros in this cohort with no incremental clinical benefit. CONCLUSIONS: A single UBT, 4 weeks after treatment is as effective as two serial breath tests in confirming H. pylori eradication. The incremental cost of the second breath test is very high with no incremental clinical benefit.

Review article: the role of surgery in gastro-oesophageal reflux disease.

BACKGROUND: Rates for laparoscopic fundoplication are declining in the United States and there is no consensus on the indications for referral to surgery in gastro-oesophageal reflux disease. AIM: To highlight recent studies on the outcomes of laparoscopic fundoplication in adults that cast doubt on the traditional indications for surgery in reflux disease. RESULTS: Patients who are well maintained on medical therapy have more to lose with surgical intervention than to gain, and should not be offered surgery. Likewise, the notion that surgery prevents oesophageal cancer is a hypothesis that is not supported by current evidence, therefore surgical intervention should not be offered to these patients. The only clear-cut candidates for surgery include: patients with anatomic abnormalities such as a large hiatus hernia, or those with persistent regurgitation that causes troublesome symptoms despite medical therapy; and carefully selected patients with extra-oesophageal disorders who have symptoms of reflux disease such as heartburn and regurgitation, an incomplete response to medical therapy and persistent plus demonstrable reflux on pH or impedance testing that is associated with their symptoms. Patients should be aware of the high likelihood of needing continued acid inhibitory therapy following surgery and the possibility of side-effects. CONCLUSION: Only a few carefully selected patients should undergo fundoplication for reflux disease.

Pretreatment endoscopy--pro & contra: is endoscopy needed before treatment in all patients with gastroesophageal reflux disease?

The role of endoscopy in reflux disease has changed from being primarily diagnostic to one of risk management. Objective studies of routine endoscopy have shown little change in outcomes after the examination. Screening and surveillance for Barrett's esophagus is still an unconfirmed strategy. In most developed countries, including western Europe and North America, middle-aged patients (over the age of 50) with gastroesophageal reflux disease would benefit more from colonoscopy than upper endoscopy.

The cost-effectiveness of biomarkers for predicting the development of oesophageal adenocarcinoma.

BACKGROUND: The recommended surveillance strategy for oesophageal adenocarcinoma may prevent as few as 50% of cancer deaths. Tissue biomarkers have been proposed to identify high-risk patients. AIM: To determine performance characteristics of an ideal biomarker, or panel of biomarkers, that would make its use more cost-effective than the current surveillance strategy. METHODS: We created a Markov model using data from published literature, and performed a cost-utility analysis. The population consisted of 50-year-old Caucasian men with gastro-oesophageal reflux, who were monitored until age 80. We examined strategies of observation only, current practice (dysplasia-guided surveillance), surveillance every 3 months for patients with a positive biomarker (biomarker-guided surveillance), and oesophagectomy immediately for a positive biomarker (biomarker-guided oesophagectomy). The primary outcome was the threshold cost and performance characteristics needed for a biomarker to be more cost-effective than current practice. RESULTS: Regardless of the cost, the biomarker needs to be at least 95% specific for biomarker-guided oesophagectomy to be cost-effective. For biomarker-guided surveillance to be cost-effective, a $100 biomarker could be 80% sensitive and specific. CONCLUSIONS: Biomarkers predicting the development of oesophageal adenocarcinoma would need to be fairly accurate and inexpensive to be cost-effective. These results should guide the development of biomarkers for oesophageal adenocarcinoma.

Review article: endoscopic treatments for gastro-oesophageal reflux disease.

A number of endoscopic techniques have been described for the treatment of reflux disease. These include endoscopic plicators, which place submucosal or transmural sutures around the lower oesophageal sphincter, the Stretta procedure, which places minute areas of thermal injury in the muscle of the lower oesophageal sphincter and cardia, and injection techniques, in which inert substances are injected into the mucosa or the muscle of the lower oesophagus. The mechanism of action of these procedures has been studied to varying degrees. The Stretta procedure is the only endoscopic technique that has been shown to be effective in a sham-controlled trial. Complication rates are generally low, but serious complications have been reported in some cases. The results with some of these techniques are promising, but all procedures described to date are limited by the absence of large, rigorously controlled trials against a form of treatment that has been proven to be both safe and effective (medical therapy). Future studies will need to use controls, validated outcome measures and pre-determined end-points and to provide comparative and long-term data.

Patient-centred endpoints in economic evaluations of gastro-oesophageal reflux disease.

AIM: To perform a systematic review of the economic literature on gastro-oesophageal reflux disease to evaluate (a) the use of patient-centred effectiveness end-points, or (b) the use of patient-centred economic end-points, and the influence of these end-points on the outcome of the model. METHODS: Three electronic databases (EMBASE, BIOSIS and Medline) were used, together with a manual search of meeting abstracts for relevant articles. The quality of the studies was determined by the Drummond criteria. RESULTS: Our initial search identified 179 articles and a manual search revealed 78 abstracts and articles. A total of 47 studies (36 fully published articles and 11 abstracts) met the seven Drummond criteria for inclusion in our evaluation. CONCLUSIONS: This systematic review demonstrates that many of the published economic evaluations available today take the perspective of the third-party payer and focus on pharmaceutical costs relevant to the third-party payer. Our study also demonstrates that there are a number of costs of illness determinations, such that pharmaceutical costs account for only a small proportion of the total costs of managing gastro-oesophageal reflux disease. Future economic analyses should consider an evaluation of the patient's desire for complete symptom relief by including cost-utility assessments or willingness to pay data.

Review article: cost-effectiveness of different GERD management strategies.

Recent data on gastro-oesophageal reflux disease management strategies suggest that the indirect costs of reflux disease are high, and that inadequate treatment is associated with significant out-patient costs for patients. Long-term management strategies now focus on discontinuous therapy for some subgroups of patients. On-demand therapy is particularly attractive for patients who have no mucosal disease.

Evidence-based health care: making health policy and management decisions.

The paradigm for health care delivery in the United States continues to evolve. Patients and physicians are beginning to reject guidelines for treatment that are solely based on cost reduction and are not evidence based. Future managed care guidelines will rely on the best external clinical evidence about the value of any given therapeutic intervention combined with individual physician experience and patient choice. Managed care organizations will need to play a greater role in the development, evaluation, and incorporation of clinical trials into their strategies.

Review article: the cost of diagnosing Helicobacter pylori infection.

Non-invasive testing and treatment for Helicobacter pylori has been recommended for dyspeptic patients in primary care and a number of recent studies have demonstrated the cost-effectiveness of this approach. As the prevalence of H. pylori infection declines, the positive and negative predictive values of individual tests will change. Cost-effectiveness is important in determining the appropriate test in individual populations. Recent studies have shown that the stool antigen test and the urea breath test have high sensitivity and specificity in the detection of H. pylori infection before and after therapy. Cost-effectiveness studies have shown that when the prevalence of H. pylori infection is low or intermediate, serological tests have relatively poor accuracy compared with the stool test or the urea breath test. In populations with low or intermediate prevalence (<60%) these tests should be preferred to ELISA serology or office-based whole-blood test or serology. This is particularly true when the prevalence of H. pylori infection is less than 30% as is seen in many developed countries. When the prevalence of H. pylori infection is high (>60%), low-cost antibody tests are cost-effective.

Endoscopy for acute nonvariceal upper gastrointestinal tract hemorrhage: is sooner better? A systematic review.

BACKGROUND: While the effectiveness of upper endoscopy has been established for acute nonvariceal upper gastrointestinal tract hemorrhage, its optimal timing has not been clearly defined. Early endoscopy has been advocated for its ability to achieve prompt diagnosis, risk stratification, and therapeutic hemostasis. OBJECTIVE: To determine whether early vs delayed endoscopy improves patient and economic outcomes for all risk groups with nonvariceal upper gastrointestinal tract hemorrhage. METHODS: A systematic review of 3 computerized databases (MEDLINE, HEALTHSTAR, and Cochrane Database of Systematic Reviews) was performed along with hand searching of published abstracts to identify English-language citations from 1980 to 2000. RESULTS: Twenty-three studies met explicit inclusion criteria. The highest-quality study examining outcomes in low-risk patients found no significant complications at 1-month follow-up for any outpatients managed with early endoscopy. The largest randomized trial of high-risk patients showed no mortality benefit but a significant decrease in transfusion requirements with early endoscopy. Seven of the 8 studies examining the effect of early endoscopy on length of stay as a measure of resource utilization demonstrated a significant reduction compared with that of delayed endoscopy. However, most included studies were found to suffer from 1 or more potentially significant methodologic shortcomings. CONCLUSIONS: The overwhelming majority of existing data suggest that early endoscopy is safe and effective for all risk groups. The clinical and economic outcomes of early endoscopy should be confirmed in additional well-designed randomized controlled trials. Given the strength of the evidence, efforts to develop a more standardized and time-sensitive approach to acute nonvariceal upper gastrointestinal tract hemorrhage should be undertaken.

Nonerosive reflux disease--current concepts and dilemmas.

Nonerosive reflux disease is defined as the presence of typical symptoms of gastroesophageal reflux disease caused by intraesophageal acid in the absence of visible esophageal mucosal injury at endoscopy. Recent studies demonstrate that it is a chronic disease with a significant impact on quality of life, and it is very common in primary care settings. Treatment with acid inhibitory agents is effective, and proton pump inhibitors are the most effective form of therapy.

The cost-effectiveness of diagnostic testing strategies for Helicobacter pylori.

OBJECTIVE: Several noninvasive methods are now available for diagnosing Helicobacter pylori infection. Because the prevalence of H. pylori infection is variable in patients requiring testing, the optimal testing strategies may vary under different conditions. The aim of this study was to evaluate the cost-effectiveness of competing diagnostic strategies for H. pylori in patients with varying H. pylori prevalence. METHODS: A decision analysis was performed comparing the costs per number of correct diagnoses achieved by alternative sequential testing strategies. Estimates of H. pylori prevalence and test characteristics were derived from a systematic review of the MEDLINE bibliographic database. Cost estimates were derived from the 2000 Medicare Fee Schedule. RESULTS: The enzyme-linked immunosorbent assay (ELISA) test had the lowest cost per correct diagnosis at low (30%), intermediate (60%), and high (90%) prevalence ($90-$95/correct diagnosis), but its diagnostic accuracy was low (80-84%). At low and intermediate prevalence the stool test was more accurate (93%), with an average cost of $126-$127 per correct diagnosis. Additional confirmatory testing of positive or negative tests increased the diagnostic accuracy of the stool test, but had high incremental costs. ELISA testing was preferable when prevalence rates were very high (90%), and using a confirmatory urea breath test for negative ELISA tests increased the diagnostic accuracy to 96%, with modest incremental costs. If the cost of the breath test was <$50 or if the cost of the stool test is >$82, breath testing became preferable to stool testing. If the cost of the stool test fell to <$20, it became preferable to ELISA. Similarly, if the cost of the ELISA serology was >$39 then stool testing became preferable at all prevalence rates. Fingerstick whole blood tests were not cost-effective. CONCLUSIONS: The choice of an initial test for H. pylori detection depends on the prevalence of H. pylori infection and the value placed on increased diagnostic accuracy. Although ELISA results in the lowest cost-effectiveness ratios, in patients at low-intermediate pretest probability of infection, the stool test provides increased accuracy, with modest incremental costs.