A model of healing of Los Angeles grades C and D reflux oesophagitis: is there an optimal time of acid suppression for maximal healing?

BACKGROUND: In patients with Los Angeles (LA) grade C or D oesophagitis, a positive relationship has been established between the duration of intragastric acid suppression and healing. AIM: To determine whether there is an apparent optimal time of intragastric acid suppression for maximal healing of reflux oesophagitis. METHODS: Post hoc analysis of data from a proof-of-concept, double-blind, randomized study of 134 adult patients treated with esomeprazole (10 or 40 mg od for 4 weeks) for LA grade C or D oesophagitis. A curve was fitted to pooled 24-h intragastric pH (day 5) and endoscopically assessed healing (4 weeks) data using piecewise quadratic logistic regression. RESULTS: Maximal reflux oesophagitis healing rates were achieved when intragastric pH >4 was achieved for approximately 50-70% (12-17 h) of the 24-h period. Acid suppression above this threshold did not yield further increases in healing rates. CONCLUSION: After 4 weeks' acid-suppressive therapy for LA grade C or D oesophagitis, successful healing appears to reach a threshold above which improvements are unlikely to be achieved despite an increase in number of hours with intragastric pH >4.

Development of the GerdQ, a tool for the diagnosis and management of gastro-oesophageal reflux disease in primary care.

BACKGROUND: Accurate diagnosis and effective management of gastro-oesophageal reflux disease (GERD) can be challenging for clinicians and other health care professionals. AIM: To develop a patient-centred, self-assessment questionnaire to assist health care professionals in the diagnosis and effective management of patients with GERD. METHODS: Questions from patient-reported GERD instruments, previously documented in terms of content validity and psychometric properties (RDQ, GSRS and GIS) and data on the diagnosis of GERD in primary and secondary care were used in the formal development of a diagnostic and management tool, the GerdQ, involving psychometric validation and piloting in patient focus groups. RESULTS: Analyses of data from over 300 primary care patients, moderated by patient input from qualitative interviews, were used to select specific items from the existing instruments to create a new six-item diagnostic and management tool (GerdQ). ROC analysis indicated a sensitivity for GerdQ of 65% and a specificity of 71% for the diagnosis of GERD, similar to that achieved by gastroenterologists. CONCLUSION: The GerdQ is a potentially useful tool for family practitioners and other health care professionals in diagnosing and managing GERD without initial specialist referral or endoscopy.

Medical or surgical management of GERD patients with Barrett's esophagus: the LOTUS trial 3-year experience.

INTRODUCTION: The long-term management of gastroesophageal reflux in patients with Barrett's esophagus (BE) is not well supported by an evidence-based consensus. We compare treatment outcome in patients with and without BE submitted to standardized laparoscopic antireflux surgery (LARS) or esomeprazole treatment. METHODS: In the Long-Term Usage of Acid Suppression Versus Antireflux Surgery trial (a European multicenter randomized study), LARS was compared with dose-adjusted esomeprazole (20-40 mg daily). Operative difficulty, complications, symptom outcomes [Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD)], and treatment failure at 3 years and pH testing (after 6 months) are reported. RESULTS: Of 554 patients with gastroesophageal reflux disease, 60 had BE-28 randomized to esomeprazole and 32 to LARS. Very few BE patients on either treatment strategy (four of 60) experienced treatment failure during the 3-year follow-up. Esophageal pH in BE patients was significantly better controlled after surgical treatment than after esomeprazole (p = 0.002), although mean GSRS and QOLRAD scores were similar for the two therapies at baseline and at 3 years. Although operative difficulty was slightly greater in patients with BE than those without, there was no difference in postoperative complications or level of symptomatic reflux control. CONCLUSION: In a well-controlled surgical environment, the success of LARS is similar in patients with or without BE and matches optimized medical therapy.

Do gastrointestinal symptoms fluctuate in the short-term perspective? The Kalixanda study.

BACKGROUND/AIM: Short-term fluctuation of gastrointestinal symptoms in the general population is largely unknown. We aimed to determine gastrointestinal symptom fluctuation in an random adult population using a validated questionnaire assessing gastrointestinal symptoms. METHODS: A representative sample (n = 2,860) of the population (n = 21,610, 20-81 years of age; mean age 50.4 years) in Northern Sweden was studied. The subjects were asked to complete the questionnaire on two occasions [mean 2.5 months (range 1-6)], firstly via mail and secondly at a visit to the clinic. An upper endoscopy was performed after the last assessment of symptoms. RESULTS: 2,122 individuals (74.2%) completed the initial questionnaire; 1,001 of these (mean age 54.1 years, 48.8 males) completed the second questionnaire. On the first occasion, 40% of the subjects were symptom-free (20.2%) or could not be classified according to their symptom pattern, of those with symptoms 39% reported troublesome reflux symptoms, 40% dyspeptic symptoms and 30% irritable bowel symptoms. Symptom overlap occurred in more than two thirds of the subjects. At the second visit 75% of the subjects who had reported dyspeptic complaints still reported such complaints. CONCLUSIONS: In this population-based study, gastrointestinal symptoms were common. Some symptom fluctuation occurred in the shorter term, but troublesome gastrointestinal complaints remained in approximately 90% of subjects over a 1-6-month period.

Comparing laparoscopic antireflux surgery with esomeprazole in the management of patients with chronic gastro-oesophageal reflux disease: a 3-year interim analysis of the LOTUS trial.

BACKGROUND: With the introduction of laparoscopic antireflux surgery (LARS) for gastro-oesophageal reflux disease (GORD) along with the increasing efficacy of modern medical treatment, a direct comparison is warranted. The 3-year interim results of a randomised study comparing both the efficacy and safety of LARS and esomeprazole (ESO) are reported. METHODS: LOTUS is an open, parallel-group multicentre, randomised and controlled trial conducted in dedicated centres in 11 European countries. LARS was completed according to a standardised protocol, comprising a total fundoplication and a crural repair. Medical treatment comprised ESO 20 mg once daily, which could be increased stepwise to 40 mg once daily and then 20 mg twice daily in the case of incomplete GORD control. The primary outcome variable was time to treatment failure (Kaplan-Meier analysis). Treatment failure was defined on the basis of symptomatic relapse requiring treatment beyond that stated in the protocol. RESULTS: 554 patients were randomised, of whom 288 were allocated to LARS and 266 to ESO. The two study arms were well matched. The proportions of patients who remained in remission after 3 years were similar for the two therapies: 90% of surgical patients compared with 93% medically treated for the intention to treat population, p = 0.25 (90% vs 95% per protocol). No major unexpected postoperative complications were experienced and ESO was well tolerated. However, postfundoplication complaints remain a problem after LARS. CONCLUSIONS: Over the first 3 years of this long-term study, both laparoscopic total fundoplication and continuous ESO treatment were similarly effective and well-tolerated therapeutic strategies for providing effective control of GORD.

Intravenous esomeprazole for prevention of peptic ulcer re-bleeding: rationale/design of Peptic Ulcer Bleed study.

BACKGROUND: A limited number of trials have investigated the efficacy of proton pump inhibitors for peptic ulcer bleeding, and some study design issues have been identified. AIM: To present the design of a large trial evaluating the effects of intravenous esomeprazole on clinical outcomes in high-risk patients who have undergone endoscopic haemostasis for peptic ulcer bleeding. METHODS: The Peptic Ulcer Bleed study is an international, randomized, double-blind, placebo-controlled trial comparing either esomeprazole 80 mg intravenous bolus infusion for 30 min followed by esomeprazole 8 mg/h intravenously for 71.5 h, or placebo infusion for 72 h, after successful endoscopic haemostasis in patients with peptic ulcer bleeding and associated high-risk stigmata. All patients will receive once daily oral esomeprazole 40 mg for 27 days after intravenous therapy. The primary end point is the rate of clinically significant re-bleeding during the first 72 h after endoscopy. Secondary end points include: rate of re-bleeding during the first 7 and 30 days after treatment; length of hospitalization; mortality; blood transfusion; endoscopic re-treatment and surgery. RESULTS: Expected 2008. CONCLUSIONS: The carefully designed protocol and quality control measures represent a pragmatic approach to contemporary challenges in peptic ulcer bleeding management and, it is hoped, qualify the Peptic Ulcer Bleed study as a new standard for future interventional studies.

Symptom overlap in patients with upper gastrointestinal complaints in the Canadian confirmatory acid suppression test (CAST) study: further psychometric validation of the reflux disease questionnaire.

BACKGROUND: The reflux disease questionnaire (RDQ) is a short, patient-completed instrument. AIMS: To investigate the psychometric characteristics of the RDQ in patients with heartburn-predominant (HB) and non-heartburn predominant (NHB) dyspepsia. METHODS: HB (n = 388) and NHB (n = 733) patients were randomized to esomeprazole 40 mg daily or twice daily for 1 week, followed by 3 weeks of esomeprazole 40 mg daily. RESULTS: High factor loadings (0.78-0.86) supported the 'regurgitation' dimension of the RDQ. Overlapping factor loadings in the 'heartburn' and 'dyspepsia' dimensions suggested symptom overlap. All dimensions demonstrated high internal consistency (Cronbach's alpha: 0.79-0.90). Intra-class correlation coefficients over 4 weeks were good (0.66-0.85). The RDQ showed good responsiveness over 4 weeks of treatment, with high effect sizes (> or =0.80). Moderate or large symptom improvements were reported by 90% and 77% of HB and NHB patients, respectively, following treatment. Patients who responded to acid suppression also experienced symptom benefits in all RDQ dimensions. CONCLUSIONS: The RDQ is reliable, valid and responsive to change in HB and NHB patients. The symptom overlap is important but need not play a major role in determining treatment strategy as both patient groups benefited from proton pump inhibitor treatment.

Predictors of treatment response in patients with non-erosive reflux disease.

BACKGROUND: Up to 40% of patients with non-erosive reflux disease (NERD) fail to respond to proton pump inhibitor therapy. AIM: To determine useful prognostic factors for response to and suppression in NERD. METHODS: A pooled analysis from three multicentre, double-blind trials of patients with a normal endoscopy and heartburn for 4 days or more during the 7 days prior to the start of each treatment. Patients received omeprazole 20 mg, esomeprazole 20 mg or esomeprazole 40 mg/day for 4 weeks. Complete resolution of heartburn was defined as no heartburn during the last week. RESULTS: Of 2458 patients included, complete heartburn resolution was achieved in 63% at the end of 4 weeks treatment. Response on days 5-7 provided an 85% probability of complete resolution of heartburn at 4 weeks; the probability of complete heartburn resolution at 4 weeks in those with moderate to severe symptoms on days 5-7 was 22%. Sensitivity and specificity of no heartburn on days 5-7 was 55% and 83% respectively. Patient demographics, duration of symptoms, medications used, other symptoms and body mass index were not predictors. CONCLUSION: Assessment of heartburn resolution during the first week of therapy was the best predictor of treatment success at 4 weeks in non-erosive reflux disease, but was suboptimal as a test.

Gastro-oesophageal reflux symptoms and health-related quality of life in the adult general population--the Kalixanda study.

BACKGROUND: The impact of gastro-oesophageal reflux symptoms on health-related quality of life in the general population is poorly characterized. AIM: To identify the frequency of troublesome reflux symptoms associated with impaired health-related quality of life in the general population. METHODS: A representative random sample of 3000 adult inhabitants of northern Sweden was surveyed using the validated Abdominal Symptom Questionnaire (response rate 74%). In total, 1001 random responders were endoscoped and assessed using the Short Form-36 Health Survey. RESULTS: Complete data were obtained for 999 subjects: 6% reported reflux symptoms (heartburn and/or regurgitation) daily, 14% weekly and 20% less than weekly during the previous 3 months. Compared with no reflux symptoms, a clinically relevant impairment of health-related quality of life (>or=5 points and P < 0.05) was seen in all eight Short Form-36 dimensions for daily symptoms, in five dimensions for weekly symptoms and in one dimension for less than weekly symptoms. There were no meaningful differences in Short Form-36 scores between subjects with and without oesophagitis. CONCLUSIONS: Most aspects of health-related quality of life were impaired in individuals with daily or weekly reflux symptoms. Troublesome reflux symptoms at least weekly may identify gastro-oesophageal reflux disease.

Patterns of gastritis and the effect of eradicating Helicobacter pylori on gastro-oesophageal reflux disease in Western patients with non-ulcer dyspepsia.

BACKGROUND: The effect of Helicobacter pylori eradication on the development of gastro-oesophageal reflux disease is controversial. Aim To determine the incidence of symptoms of reflux disease and of erosive oesophagitis, and the relationship to changes in histological gastritis, in patients with non-ulcer dyspepsia over 12 months. METHODS: Six hundred and ninety-three patients in two similar randomized placebo controlled trials of H. pylori eradication in non-ulcer dyspepsia were studied. Symptoms were assessed using the validated Gastrointestinal Symptom Rating Scale during a 1-week run-in period, at 6 months and 12 months. Endoscopy was performed at baseline to exclude patients with pathology and at 3 months and 12 months to determine if oesophagitis was present. Gastric biopsies were scored using the modified Sydney Classification. RESULTS: Patients without predominant heartburn, oesophagitis or ulcers at endoscopy were randomized to active (n = 297, omeprazole, amoxicillin and clarithromycin) treatment or to placebo/omeprazole (n = 306) for 1 week. The eradication rate was 82% in the active treatment group. Antrum-predominant gastritis (55%) was more frequently found than corpus-predominant gastritis (6%). In patients with antrum-predominant gastritis, heartburn and regurgitation scores improved significantly 12 months after eradication. Erosive oesophagitis developed in 15/232 patients in the eradication group (7%) compared with 2/227 (2%) in the control group, but there was no significant difference when adjusted for oesophagitis present at baseline. CONCLUSIONS: Antrum-predominant gastritis is the most common pattern of gastritis seen in non-ulcer dyspepsia in Western populations. Heartburn and regurgitation improve after eradication therapy or placebo in patients with non-ulcer dyspepsia; the development of oesophagitis is uncommon.

Prognostic influence of Barrett's oesophagus and Helicobacter pylori infection on healing of erosive gastro-oesophageal reflux disease (GORD) and symptom resolution in non-erosive GORD: report from the ProGORD study.

BACKGROUND: Adequacy of acid suppression is a critical factor influencing healing in gastro-oesophageal reflux disease (GORD). The European prospective study ProGORD was set up to determine the endoscopic and symptomatic progression of GORD over five years under routine care, after initial acid suppression with esomeprazole. We report on factors influencing endoscopic healing and symptom resolution during the acute treatment phase. METHODS: Patients with symptoms suggestive of GORD underwent endoscopy and biopsies were obtained from the oesophagus for diagnosis of abnormalities, including Barrett's oesophagus (BO). Data from 6215 patients were included in the "intention to treat" analysis, 3245 diagnosed as having erosive reflux disease (ERD) and 2970 non-erosive reflux disease (NERD). ERD patients were treated with esomeprazole 40 mg for 4-8 weeks for endoscopic healing while NERD patients received 20 mg for 2-4 weeks for resolution of heartburn symptoms. RESULTS: Endoscopic healing occurred overall in 87.7% of ERD patients although healing was significantly lower in those with more severe oesophagitis (76.9%) and in those with BO (72.4%), particularly in Helicobacter pylori negative BO patients (70.1%). Age, sex, and body mass index appeared to have no significant impact on healing. Complete heartburn resolution was reported by 70.4% of ERD patients and by 64.8% of NERD patients at the last visit. Only H pylori infection had a significant influence on complete heartburn resolution in the NERD group (68.1% and 63.7% for H pylori positive and H pylori negative, respectively; p = 0.03). CONCLUSION: The presence of Barrett's mucosa, as well as severe mucosal damage, exerts a negative impact on healing. H pylori infection had a positive influence on healing in ERD patients with coexistent BO but no influence on those without BO.

The role of acid suppression in patients with endoscopy-negative reflux disease: the effect of treatment with esomeprazole or omeprazole.

BACKGROUND: Patients with endoscopy-negative reflux disease have reflux symptoms, mainly heartburn, but not mucosal breaks characteristic of erosive oesophagitis. Standard-dose proton pump inhibitors can provide symptom relief in endoscopy-negative reflux disease but the effect of greater acid suppression has not been studied. AIM: To test the hypothesis that esomeprazole produces heartburn resolution in a greater proportion of patients with ENRD than omeprazole. METHODS: Three multi-centre randomized, controlled, double-blind, 4-week acute treatment studies were conducted in endoscopy-negative reflux disease patients. In study A (n = 1282), patients received either esomeprazole 40 mg, esomeprazole 20 mg or omeprazole 20 mg daily; in studies B (n = 693) and C (n = 670) patients received either esomeprazole 40 mg or omeprazole 20 mg (B), and esomeprazole 20 mg or omeprazole 20 mg (C), respectively. RESULTS: Resolution of heartburn at 4 weeks (no heartburn symptoms during the last 7 days) was achieved in similar proportions of patients in each treatment arm in study A (esomeprazole 40 mg, 56.7%; esomeprazole 20 mg, 60.5%; omeprazole 20 mg, 58.1%), study B (esomeprazole 40 mg, 70.3%; omeprazole 20 mg, 67.9%) and study C (esomeprazole 20 mg, 61.9%; omeprazole 20 mg, 59.6%). There were no significant differences between treatment groups within each study. CONCLUSIONS: More than 60% of endoscopy-negative reflux disease patients reported heartburn resolution but, after 4 weeks of therapy, these proportions did not differ significantly between treatments.

Validation of the translation and cross-cultural adaptation into Finnish of the Abdominal Symptom Questionnaire, the Hospital Anxiety and Depression Scale and the Complaint Score Questionnaire.

BACKGROUND: Epidemiological surveys require questionnaires to be validated in the native language of the participants. The aim of this study was to validate the Finnish translations of the Abdominal Symptom Questionnaire (ASQ), the Hospital Anxiety and Depression Scale (HAD) and the Complaint Score Questionnaire (CSQ). METHODS: A random sample of adults (n = 3000) in a northern Swedish bilingual district was surveyed using a mailed ASQ offered in both SwedIsh and Finnish, and 2122 responded (239 in Finnish). A random subsample of the responders (n = 1001, 123 preferring Finish) was then surveyed once more using the ASQ, the HAD and the CSQ. The first 50 responders of the latter survey were then given the three questionnaires again within two weeks. The Finnish versions had been put through a comprehensive translation procedure RESULTS: A factor analysis comparison between the responders using either language in the mailed survey gave a comparable factor construction, and this was also comparable with an earlier analysis of the Swedish version. The Finnish responses to the second survey were further evaluated by testing internal consistency reliability, convergent validity towards previously validated relevant instruments (ShortForm-36 and the Gastrointestinal Symptom Rating Scale) and the test/re-test accuracy of the three questionnaires. These were found to be reliable, as was the correlation between the ASQ and the CSQ, for relevant domains. CONCLUSION: The Finnish translations of the ASQ, HAD and CSQ questionnaires all seem to be robust and usable for population-based surveys among Finnish adults.

Is it possible to predict treatment response to a proton pump inhibitor in functional dyspepsia?

BACKGROUND: The efficacy of proton pump inhibitors in functional dyspepsia is modest and the prognostic factors are almost unknown. METHODS: Data were pooled on patients (n = 826) with a diagnosis of functional dyspepsia from two placebo-controlled trials who were treated with omeprazole, 10 or 20 mg once daily, for 4 weeks. Self-administered questionnaires for the assessment of symptoms and health-related quality of life were completed before entry, and epigastric pain/discomfort was recorded on diary cards. Treatment success was defined as the complete absence of epigastric pain/discomfort on each of the last 3 days of week 4. Prognostic factors were identified by multiple logistic regression analysis. RESULTS: The most discriminating predictor of treatment success (P < 0.0001) was the number of days with epigastric pain/discomfort during the first week of treatment. Fewer days with symptoms during the first week led to higher response rates at 4 weeks. In addition, age > 40 years, bothersome heartburn, low scores for bloating, epigastric pain and diarrhoea, history of symptoms for < 3 months and low impairment of vitality at baseline were identified as positive predictors of outcome. CONCLUSIONS: Early response to treatment with a proton pump inhibitor, during the first week, seems to predict the outcome after 4 weeks in patients with functional dyspepsia.

Combined analysis of the ORCHID and OCAY studies: does eradication of Helicobacter pylori lead to sustained improvement in functional dyspepsia symptoms?

Currently, one of the most important unresolved questions concerning Helicobacter pylori is whether eradication of the organism leads to a sustained improvement in symptoms in patients diagnosed with functional (non-ulcer) dyspepsia. Recently, two very similar studies, the ORCHID and OCAY studies, have been completed and the combined results of these two multicentre, multinational, randomised, double blind, controlled clinical trials are reviewed.

Self-administered symptom questionnaires in patients with dyspepsia and their yield in discriminating between endoscopic diagnoses.

BACKGROUND/AIMS: Symptoms are generally considered to be poor predictors of organic findings in patients with dyspepsia. We aimed at evaluating whether specific gastrointestinal symptoms, identified by self-administered questionnaires, correlate with specific endoscopic diagnoses and discriminate organic from functional dyspepsia. METHODS: Adult patients with pain or discomfort centred in the upper abdominal region were consecutively enrolled. Patients with heartburn, acid regurgitation, or defaecation and bowel habit problems as their predominant symptoms were excluded. Three self-administered questionnaires were applied before an oesophagogastroduodenoscopy was performed. RESULTS: Among the 799 patients, 50.6% had a normal endoscopy. Endoscopic diagnoses comprised: non-erosive oesophagitis (7.5%), erosive oesophagitis (11.1%), Barrett's oesophagus (1.1%), gastritis/duodenitis (8.4%), gastric ulcer (4.5%), duodenal ulcer (8.3%), and cancer (1.3%). Non-dominant heartburn and acid regurgitation were significantly more common in patients with organic dyspepsia, whereas hunger pains and rumbling occurred more often in those with functional dyspepsia. Multivariate analyses demonstrated that younger age, female gender, high scores for hunger pain, rumbling, hard stools, low scores for heartburn, and acid regurgitation predicted functional dyspepsia. CONCLUSIONS: Self-administered questionnaires revealed differences in the symptom patterns between patients with functional and organic dyspepsia. Furthermore, the health-related well-being in patients with functional and organic dyspepsia centred was impaired to the same extent.

Effect of profound acid suppression in functional dyspepsia: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Functional dyspepsia (FD) is defined as persistent or recurrent pain/discomfort centred in the upper abdomen, where no structural explanation for the symptoms is found. The role of drug treatment remains controversial. The aim in this study was to evaluate the effect of omeprazole 20 mg twice daily (b.i.d) and to test methods for symptom assessment. METHODS: 197 patients fulfilling the criteria for FD were randomly allocated to double-blind treatment with omeprazole 20 mg b.i.d (n = 100) or placebo (n = 97) for 14 days. Patients with a known gastrointestinal disorder or with main symptoms indicating gastro-oesophageal reflux disease or irritable bowel syndrome were excluded. Helicobacter pylori testing and 24-h intra-oesophageal 24-h pH-metry were performed before randomization. The patients recorded dyspeptic symptoms on diary cards. RESULTS: A stringent endpoint, 'complete symptom relief on the last day of treatment', was the primary efficacy variable. For the APT cohort, this was achieved in 29.0% and 17.7% on omeprazole and placebo, respectively (95% CI of difference (11.3%): -0.4%-23.0%, P = 0.057). Similar figures in the PP cohort were 31.0% and 15.5%, respectively (95% Cl of difference (15.5%): 3.2%-27.7%, P = 0.018). The benefit of omeprazole in the PP cohort was confirmed by secondary endpoints such as, no dyspeptic symptoms on the last 2 days of treatment and overall treatment response. H. pylori status and the level of oesophageal acid exposure did not significantly influence the response to therapy. CONCLUSION: A subset of patients with FD will respond to therapy with omeprazole.

Quality of life in patients with endoscopy-negative heartburn: reliability and sensitivity of disease-specific instruments.

OBJECTIVES: Endoscopy-negative gastroesophageal reflux disease (GERD) lacks objective markers of disease severity. Evaluation of therapies for GERD must therefore rely on subjective measures, including patient self-report questionnaires, to measure the clinical effectiveness of therapeutic interventions. We aimed to evaluate the previously validated Gastrointestinal Symptoms Rating Scale (GSRS) and the Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaires for reliability and responsiveness to change over time. METHODS: Patients (n = 1143) with heartburn, but no esophagitis included in a randomized clinical trial assessing the effectiveness of active treatment with proton pump inhibitors over 4 wk were evaluated. RESULTS: The test-retest reliability of both questionnaires over time was good to excellent (GSRS 0.53-0.69; QOLRAD 0.65-0.76), as was the responsiveness estimated by standardized response means (GSRS reflux dimension, -1.43; QOLRAD 0.81-1.43) and effect sizes (GRSR reflux dimension, -1.74; QOLRAD 0.82-1.56). The relationship between improvement in the GSRS reflux dimension score and the amount of clinical benefit as estimated by the patients themselves (based on the Overall Treatment Evaluation) suggested a minimally clinical relevant change is 0.5 on the seven graded scales applied. The importance rating indicated that an important change in the GSRS reflux dimension and the QOLRAD dimensions is equivalent to 1.0, and a very important change to 1.5. CONCLUSIONS: The GSRS and QOLRAD are valid questionnaires that are reliable and sensitive to change. Both questionnaires should be suitable for use in clinical trials of therapeutic interventions for patients with heartburn.

Esomeprazole 20 mg maintains symptom control in endoscopy-negative gastro-oesophageal reflux disease: a controlled trial of 'on-demand' therapy for 6 months.

BACKGROUND: Most patients with gastro-oesophageal reflux disease (GERD), regardless of endoscopic status, suffer symptomatic relapse within 6 months of stopping acid suppressant therapy. AIM: To assess the efficacy of 'on-demand' treatment of GERD with esomeprazole, the first proton pump inhibitor developed as an optical isomer. METHODS: In this multicentre, double-blind study, 342 endoscopy-negative GERD patients demonstrating complete resolution of heartburn during the final week of a 4-week treatment period with esomeprazole 20 mg or omeprazole 20 mg once daily were randomized to receive esomeprazole 20 mg or placebo on demand (maximum of one dose per day) for a further 6 months. Use of rescue antacids was permitted. RESULTS: All 342 patients (191 males), aged 19-79 (mean 49) years, were evaluable in the intention-to-treat analysis. The proportion of patients who discontinued treatment due to insufficient control of heartburn was significantly higher among placebo compared to esomeprazole recipients (51% vs. 14%; P < 0.0001). Patients randomized to esomeprazole on-demand therapy remained in the study longer than those in the placebo group (mean 165 vs. 119 days). Over 50% took the study medication for periods of 1--3 consecutive days (esomeprazole) or 4--13 consecutive days (placebo). Use of antacids was > 2-fold higher among placebo recipients. The frequency of adverse events was similar in the two groups, when adjusted for time spent in the study, as were the clinical laboratory profiles. CONCLUSIONS: On-demand therapy with esomeprazole 20 mg is effective and well tolerated in maintaining symptom control in endoscopy-negative GERD.