Ola Junghard

Gastro-oesophageal reflux disease in primary care: an international study of different treatment strategies with omeprazole

Objective To assess the efficacy of omeprazole in patients presenting with troublesome reflux symptoms. Design Randomized, double-blind, parallel-group, placebo-controlled comparison. Subjects Patients were recruited using a symptom-based questionnaire for diagnosis of gastro-oesophageal reflux disease. Interventions After endoscopy, patients without endoscopie 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 Gl symptom relief during week 4 on Ome20 or Ome10 in patients with or without endoscopie oesophagitis. Results Forty one percent of all patients on Ome20 and 35% on Ome10 reported complete relief from upper Gl 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%. Endoscopie 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.

Lack of Effect of Treating Helicobacter pylori Infection in Patients with Nonulcer Dyspepsia

BACKGROUND It is uncertain whether treatment of Helicobacter pylori infection relieves symptoms in patients with nonulcer, or functional, dyspepsia. METHODS We conducted a double-blind, multicenter trial of patients with H. pylori infection and dyspeptic symptoms (moderate-to-very-severe pain and discomfort centered in the upper abdomen). Patients were excluded if they had a history of peptic ulcer disease or gastroesophageal reflux disease and had abnormal findings on upper endoscopy. Patients were randomly assigned to seven days of treatment with 20 mg of omeprazole twice daily, 1000 mg of amoxicillin twice daily, and 500 mg of clarithromycin twice daily or with omeprazole alone and then followed up for one year. Treatment success was defined as the absence of dyspeptic symptoms or the presence of minimal symptoms on any of the 7 days preceding the 12-month visit. RESULTS Twenty of the 348 patients were excluded after randomization because they were not infected with H. pylori, were not treated, or had no data available. For the remaining 328 patients (164 in each group), treatment was successful for 27.4 percent of those assigned to receive omeprazole and antibiotics and 20.7 percent of those assigned to receive omeprazole alone (P=0.17; absolute difference between groups, 6.7 percent; 95 percent confidence interval, -2.6 to 16.0). After 12 months, gastritis had healed in 75.0 percent of the patients in the group given omeprazole and antibiotics and in 3.0 percent of the patients in the omeprazole group (P<0.001); the respective rates of H. pylori eradication were 79 percent and 2 percent. In the group given omeprazole and antibiotics, the rate of treatment success among patients with persistent H. pylori infection was similar to that among patients in whom the infection was eradicated (26 percent vs. 31 percent). There were no significant differences between the groups in the quality of life after treatment. CONCLUSIONS In patients with nonulcer dyspepsia, the eradication of H. pylori infection is not likely to relieve symptoms.

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.

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

Most patients with gastro‐oesophageal reflux disease (GERD), regardless of endoscopic status, suffer symptomatic relapse within 6 months of stopping acid suppressant therapy.

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.

Accuracy of the diagnosis of GORD by questionnaire, physicians and a trial of proton pump inhibitor treatment: the Diamond Study

Objective The aim of this study was to determine the accuracy of the diagnosis of gastro-oesophageal reflux disease (GORD) by the Reflux Disease Questionnaire (RDQ), family practitioners, gastroenterologists and a test of esomeprazole therapy. Methods This was a single-blind, single-arm study over 3–4 weeks from September 2005 to November 2006. Each symptom-based diagnostic assessment was made blinded to prior diagnoses. Patients were those presenting to their family practitioner with troublesome upper gastrointestinal symptoms (n=308). The RDQ was completed and a symptom-based diagnosis was made by the family practitioner. Placebo esomeprazole was started. Gastroenterologists made a symptom-based diagnosis and then performed endoscopy with 48 h oesophageal pH and symptom association monitoring to determine the presence/absence of GORD. Symptoms were recorded during treatment with 40 mg of esomeprazole for 2 weeks. The main outcome measure was RDQ scoring for the presence of GORD compared with symptom-based diagnosis by family physicians and gastroenterologists. Results GORD was present in 203/308 (66%) patients. Only 49% of the patients with GORD selected either heartburn or regurgitation as the most troublesome symptom. Sensitivity and specificity, respectively, of the symptom-based diagnosis of GORD, were 62% and 67% for the RDQ, 63% and 63% for family practitioners, and 67% and 70% for gastroenterologists. Symptom response to esomeprazole was neither sensitive nor specific for the diagnosis of GORD. Conclusions The RDQ, family practitioners and gastroenterologists have moderate and similar accuracy for diagnosis of GORD. Symptom response to a 2 week course of 40 mg of esomeprazole does not add diagnostic precision. Clinical trial number NCT00291746.

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.

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

The impact of gastro‐oesophageal reflux symptoms on health‐related quality of life in the general population is poorly characterized.

Effect of esomeprazole 40 mg once or twice daily on asthma: a randomized, placebo-controlled study.

RATIONALE Gastroesophageal reflux disease (GERD) is common among patients with asthma; however, studies investigating the effect of proton pump inhibitors on asthma outcomes report conflicting results. OBJECTIVES To investigate the effect of esomeprazole 40 mg once or twice daily on asthma outcomes in patients with concomitant symptoms of GERD. METHODS This 26-week, randomized, double-blind, placebo-controlled study (NCT00317044) included adult patients (18-70 yr) with moderate-to-severe asthma and symptomatic GERD. The change in morning peak expiratory flow (primary variable), evening peak expiratory flow, FEV(1), asthma symptoms, Asthma Quality of Life Questionnaire, Reflux Disease Questionnaire, and tolerability were assessed. MEASUREMENTS AND MAIN RESULTS A total of 961 patients were randomized and 828 completed the study. Relative to baseline, improvement in morning peak expiratory flow was observed for both esomeprazole 40 mg once daily (+3.5 L/min; 95% CI, -3.2 to 10.2) and 40 mg twice daily (+5.5 L/min; 95% CI, -1.2 to 12.2), although no statistically significant between-treatment differences were apparent. At treatment end, both doses of esomeprazole significantly improved FEV(1) versus placebo (+0.09 L and +0.12 L; P = 0.0039 and P < 0.0001, respectively). However, only esomeprazole 40 mg twice daily demonstrated a significant improvement when FEV(1) was calculated over the entire 26-week period (+0.07 L; P = 0.0042). Significant improvements in Asthma Quality of Life Questionnaire total score were demonstrated for both esomeprazole doses compared with placebo (+0.28 and +0.41; P = 0.0006 and P < 0.0001, respectively). CONCLUSIONS Esomeprazole may improve pulmonary function and asthma-related quality of life. However, the improvements were minor and of small clinical significance.

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.