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.

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.

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.

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.

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.

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.

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.

On demand therapy with omeprazole for the long-term management of patients with heartburn without oesophagitis--a placebo-controlled randomized trial.

AIM: To observe the natural course of gastro-oesophageal reflux disease (GERD) in patients without oesophagitis following effective symptom relief, and to determine the place of acid pump inhibitor therapy in the long-term management of these patients. METHODS: We investigated the efficacy of on-demand therapy with omeprazole 20 mg or 10 mg, or placebo in a double-blind, randomized multicentre trial. It involved 424 patients with troublesome heartburn without endoscopic evidence of oesophagitis in whom heartburn had been resolved with short-term treatment. Patients were told to take study medication on demand once daily on recurrence of symptoms until symptoms resolved over a 6-month period. They also had access to antacids. The primary efficacy variable was time to discontinuation of treatment, due to unwillingness to continue. RESULTS: According to life-table analysis, after 6 months the remission rates were 83% (95% CI: 77-89%) with omeprazole 20 mg, 69% (61-77%) with omeprazole 10 mg, and 56% (46-64%) with placebo (P < 0.01 for all intergroup differences). The mean (s.d.) number of study medications used per day in these groups was 0.43 (0.27), 0.41 (0.27) and 0.47 (0.27), respectively. The use of antacids was highest in the placebo group and lowest in the omeprazole 20 mg group. Treatment failure was associated with more than a doubling of antacid use, and a deterioration in patient quality of life. CONCLUSIONS: Approximately 50% of patients with heartburn who do not have oesophagitis need acid inhibitory therapy in addition to antacid medication to maintain a normal quality of life. On-demand therapy with omeprazole 20 mg, is an effective treatment strategy in these patients.

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.

Gastro-oesophageal reflux disease in primary care: an international study of different treatment strategies with omeprazole. International GORD Study Group.

OBJECTIVE: To assess the efficacy of omeprazole in patients presenting with troublesome reflux symptoms. DESIGN: Randomized, double-blind, parallel-group, placebo-controlled comparison. SETTING: Primary care. SUBJECTS: Patients were recruited using a symptom-based questionnaire for diagnosis of gastro-oesophageal reflux disease. INTERVENTIONS: After endoscopy, patients without endoscopic oesophagitis were randomized to omeprazole 20 mg (Ome20), omeprazole 10 mg (Ome10) or placebo once daily for 4 weeks (n = 261) and those with oesophagitis (except circumferential/ulcerative) were randomized to receive either Ome20 or Ome10 once daily for 4 weeks (n = 277). Patients not symptom-free at 4 weeks received open treatment with Ome20 once daily for a further 4 weeks. Those symptom-free at 4-8 weeks were followed up for 6 months off treatment, to see whether their symptoms recurred. MAIN OUTCOME MEASURE: Complete upper GI symptom relief during week 4 on Ome20 or Ome10 in patients with or without endoscopic oesophagitis. RESULTS: Forty one percent of all patients on Ome20 and 35% on Ome10 reported complete relief from upper GI symptoms during week 4, whilst 73% of the patients on Ome20 and 62% on Ome10 obtained sufficient control. Complete relief during week 4 was reported by 19% of endoscopy-negative patients on placebo, and sufficient control by 35%. Endoscopic healing at 4 weeks occurred in 76% of oesophagitis patients on Ome20 and in 56% on Ome10. After 6 months off treatment, 90% of patients with oesophagitis and 75% of endoscopy-negative patients reported symptomatic relapse. CONCLUSION: Both 10 mg and 20 mg of omeprazole gave effective relief of symptoms, although 20 mg gave superior healing in patients with oesophagitis. After cessation of treatment, symptomatic relapse was rapid and frequent in both endoscopy-positive and endoscopy-negative patients.

Estimating the traffic safety effect of studded tires.

Swedish accident and exposure data from December 1989 to February 1990 are used to estimate the risk of involvement in an accident on a slippery road when using studded tires compared with the risk when driving with summer tires. Two methods have been used, one involving both accident and exposure data, the other using only accident data. Both methods give similar estimates, indicating that studded tires reduce the risk of involvement in slippery road accidents by 20%-50%.

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.

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.

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.

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.

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.

Validation of seven graded diary cards for severity of dyspeptic symptoms in patients with non ulcer dyspepsia.

The diary card as a measure of the severity of pain or discomfort in the stomach on a 7 graded scale was validated using data from a randomised placebo controlled clinical trial in patients with non-ulcer dyspepsia (NUD). The diary card measure was compared to two other measures: a symptom question in a gastro-intestinal symptom questionnaire and a symptom severity rating made by the investigator based on an interview with the patient at the clinical visit. The reliability coefficient for the mean of the diary card scores from 7 consecutive days was estimated to 0.71. The mean of the scores from 7 consecutive days was approximately as sensitive to change as the other two measures.

Omeprazole for treatment of chronic erosive esophagitis in children: a multicenter study of efficacy, safety, tolerability and dose requirements. International Pediatric Omeprazole Study Group.

OBJECTIVES: To determine the efficacy, safety, and tolerability of omeprazole in children and to determine the doses required to heal chronic, severe esophagitis. STUDY DESIGN: Open multicenter study in children aged 1 to 16 years with erosive reflux esophagitis. The healing dose of omeprazole used was that with which the duration of acid reflux was <6% of a 24-hour intraesophageal pH study. Follow-up endoscopy was performed after 3 months of treatment with the healing dose. RESULTS: At entry, two thirds of 57 patients who completed the study had esophagitis grade 3 or 4 (scale 0-4); some 50% had neurologic impairment or repaired esophageal atresia. Of the 57 patients, 54 healed; 3 did not heal and left the study, and 3 healed with a second course. Doses required for healing were 0.7 to 3.5 mg/kg/d: 0.7 mg/kg/d in 44% of patients and 1.4 mg/kg/d in another 28%. Healing dose correlated with grade of esophagitis but not with age or underlying disease. Reflux symptoms improved dramatically in almost all of the 57 patients, including the unhealed patients. CONCLUSIONS: Omeprazole is well tolerated, highly effective, and safe for treatment of erosive esophagitis and symptoms of gastroesophageal reflux in children, including children in whom antireflux surgery or other medical therapy has failed. On a per-kilogram basis, the doses of omeprazole required to heal erosive esophagitis are much greater than those required for adults.