Do we need a new gastro‐oesophageal reflux disease questionnaire?

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is highly prevalent in Western countries. Because the majority of patients do not present with endoscopic abnormalities, the assessment of the symptom severity and quality of life, and their response to treatment, has become increasingly important. Self-assessed symptom questionnaires are now key instruments in clinical trials. AIM: To evaluate the validity of available GERD measurement tools. METHODS: An ideal GERD symptom assessment instrument, suitable as a primary end-point for clinical trials, should possess the following characteristics: (i) be sensitive in patients with GERD; (ii) cover the frequency and intensity of typical and atypical GERD symptoms; (iii) be multidimensional (cover all symptom dimensions); (iv) have proven psychometric properties (validity, reliability and responsiveness); (v) be practical and economical; (vi) be self-assessed; (vii) use 'word pictures' which are easy to understand for patients; (viii) respond rapidly to changes (responsiveness over short time intervals); (ix) be used daily to assess changes during and after therapy; and (x) be valid in different languages for international use. RESULTS: A literature review revealed five scales that met some of the above characteristics, but did not fulfil all criteria. CONCLUSION: There is a need for a new evaluative tool for the assessment of GERD symptoms and their response to therapy.     

Systematic review: does gastro‐oesophageal reflux disease progress?

BACKGROUND: Gastro-oesophageal reflux disease affects approximately 20% of western populations. Barrett's oesophagus, associated with severe gastro-oesophageal reflux disease, is premalignant and regular endoscopic surveillance is generally performed. In contrast, mild gastro-oesophageal reflux disease is thought not to progress and is not generally subjected to endoscopic follow-up. Aim To investigate whether gastro-oesophageal reflux disease progresses endoscopically. METHODS: Systematic review of the literature. RESULTS: Well-designed prospective studies are few, diagnostic criteria were not always standardized, management strategies varied and various sources of bias could not be excluded. Whilst most patients do not progress to more severe forms of gastro-oesophageal reflux disease, and some cases actually regress, progression is seen in a small proportion of patients. Annual progression rates for non-erosive gastro-oesophageal reflux disease developing erosive oesophagitis ranged from 0% to 30%. About 1-22% of patients with mild erosive oesophagitis developed more severe inflammation annually, while 1-13% of patients with erosive oesophagitis developed Barrett's oesophagus each year. CONCLUSION: Although most patients with gastro-oesophageal reflux disease do not progress, and some actually regress, progression does occur in a minority. Better data are required to determine whether patients with mild gastro-oesophageal reflux disease would benefit from increased surveillance with the aim of detecting more advanced disease.     

Do physicians correctly assess patient symptom severity in gastro‐oesophageal reflux disease?

BACKGROUND: The accuracy of physicians' assessment of the severity of gastro-oesophageal reflux disease is unclear. AIM: To correlate physician and patient assessment of gastro-oesophageal reflux disease severity and its response to treatment. METHODS: Adult uninvestigated gastro-oesophageal reflux disease patients (n = 217) completed symptom and health-related quality of life questionnaires at baseline and after treatment with esomeprazole 40 mg p.o. daily. Pearson coefficients quantified correlations between physician assessments and patient responses. RESULTS: At baseline, the strongest correlations were heartburn severity (0.31), overall symptom severity (0.44) and a domain of the quality of life in reflux and dyspepsia questionnaire (0.31) (P < 0.001). Correlations of change with treatment were greater than baseline correlations: heartburn (0.39), overall symptoms (0.50) and global rate of change -- stomach problems (0.72, all P < 0.001). The mean difference between the physicians' assessment of change and the patients' global rating of change was 0.20 (95% confidence intervals: 0.10-0.29) with physicians overestimating benefit. CONCLUSIONS: Correlations were often significant, although weak to moderate and better with symptom severity than with health-related quality of life instruments as well as with change after therapy than at baseline. Increasing attention to health-related quality of life may help physicians better understand patients' experience. In clinical trials, treatment success should be assessed by the patient as well as the physician.     

Does Barrett's oesophagus develop over time in patients with chronic gastro‐oesophageal reflux disease?

BACKGROUND: Barrett's oesophagus is present in 8-10% of patients with gastro-oesophageal reflux disease (GERD). AIM: We performed a cohort study to determine the incidence of Barrett's oesophagus in patients with chronic heartburn symptoms. METHODS: We identified patients, with GERD and/or Barrett's oesophagus between 1998 and 2004 by primary or secondary International Classification of Diseases (ICD-9) codes of 530.81 and/or 530.2, who had two or more oesophagogastroduodenoscopies performed at least 6 months apart. RESULTS: We screened 11 040 patients (41 390 random data entries by ICD-9 code) and enrolled 515 (4.6%) GERD patients and 169 (1.5%) Barrett's oesophagus patients. The mean (+/-s.d.) number of oesophagogastroduodenoscopies in the GERD cohort was 3.2 +/- 1.8 (range: 2-15) over 3.4 +/- 2.2 (range: 0.5-11) years. None of the 412 (80%) GERD patients with non-erosive disease developed Barrett's oesophagus over a mean follow-up time of 3.4 +/- 2.2 years (95% CI: 0-0.9%). Five (1%) of the 103 GERD patients with erosive oesophagitis developed subsequent Barrett's oesophagus. Fifty-seven per cent of the GERD patients were on PPI therapy at the time of index endoscopy. None of the 169 Barrett's oesophagus patients had normal index oesophagogastroduodenoscopies within a mean retrospective time period of 4.5 +/- 2.8 years (95% CI: 0-2%). Using the ICD-9 code of 530.2 as a predictor of the presence of Barrett's oesophagus, the sensitivity was 79% with a specificity of 88%. CONCLUSION: The majority of patients with GERD do not appear to develop Barrett's oesophagus when it is not present on the index endoscopy.     

Is there any association between myocardial infarction,gastro‐oesophageal reflux disease and acid‐suppressing drugs?

BACKGROUND: A link between gastro-oesophageal reflux disease and coronary heart disease has been suggested. AIM: To estimate the incidence of myocardial infarction in patients with newly diagnosed gastro-oesophageal reflux disease in comparison with that in the general population. METHODS: A population-based cohort study was performed in the UK. Patients aged 18-79 years with a first diagnosis of gastro-oesophageal reflux disease (n = 7084) were identified and a group of 10,000 patients free of gastro-oesophageal reflux disease were sampled. A nested case-control analysis was performed to assess the risk factors for myocardial infarction. RESULTS: The incidence of myocardial infarction in the general population was 4.0 per 1,000 person-years [95% confidence interval (CI), 3.2-4.9] and 5.1 per 1,000 person-years (95% CI, 4.1-6.4) in patients with gastro-oesophageal reflux disease. The relative risk of myocardial infarction in patients with gastro-oesophageal reflux disease was 1.4 (95% CI, 1.0-1.9). The increased risk of myocardial infarction was limited to the immediate days after the diagnosis of gastro-oesophageal reflux disease. Previous chest pain was an important predictor of myocardial infarction in patients free of gastro-oesophageal reflux disease. No association was found between the use of acid-suppressing drugs and the risk of myocardial infarction. CONCLUSION: Our results suggest that gastro-oesophageal reflux disease is not an independent predictor of myocardial infarction. Rather, the increased risk of myocardial infarction in patients with gastro-oesophageal reflux disease in the immediate days after diagnosis indicates that prodromal ischaemic symptoms were misinterpreted as reflux symptoms.     

Systematic review: proton‐pump inhibitor failure in gastro‐oesophageal reflux disease – where next?

Proton-pump inhibitor failure has become a common clinical dilemma in gastrointestinal clinics and has been increasingly encountered at the primary care level as well. Underlying mechanisms are diverse and may overlap. Most patients who have proton-pump inhibitor failure are likely to originate from the non-erosive reflux disease phenotype. Currently, available diagnostic modalities provide limited clues to the exact underlying cause. Treatment relies primarily on escalating dosing of proton-pump inhibitors. However, new insights into the pathophysiology of proton-pump inhibitor failure are likely to provide alternative therapeutic options.     

Personal view: to treat or not to treat? Helicobacter pylori and gastro‐oesophageal reflux disease — an alternative hypothesis

Helicobacter pylori causes acute on chronic gastritis and is responsible for most peptic ulcers and gastric cancer. However, recent papers have suggested that it may protect against gastro-oesophageal reflux, Barrett's oesophagus and oesophageal cancer. Furthermore, the rapid increase in gastro-oesophageal reflux disease, Barrett's oesophagus and adenocarcinoma of the oesophagus in the developed world has been attributed by some to the falling prevalence of H. pylori. These considerations have led to the suggestion that H. pylori infection should not necessarily be treated, especially in patients with gastro-oesophageal reflux disease. Conversely, data from prospective randomized studies have shown that H. pylori eradication does not cause gastro-oesophageal reflux disease in patients with duodenal ulcer or in the normal population, nor does it worsen the outcome of pre-existing gastro-oesophageal reflux disease. Therefore, although H. pylori is negatively associated with gastro-oesophageal reflux disease, its eradication does not induce the disease. A hypothesis is presented suggesting that the increased prevalence of gastro-oesophageal reflux disease is a result of rising acid secretion in the general population, which, in turn, is a consequence of the increased linear height (a predictor of acid secretion). The greater acid secretion could also explain the decline in the prevalence of H. pylori and perhaps account for the inverse relationship between H. pylori and gastro-oesophageal reflux disease. These considerations are explored in discussing whether H. pylori infection should be treated in infected patients presenting with gastro-oesophageal reflux disease.     

Does body mass index differ between patients with Barrett’s oesophagus and patients with chronic gastro‐oesophageal reflux disease?

BACKGROUND: Obesity has been demonstrated to be a risk factor for the development of gastro-oesophageal reflux disease (GERD). AIM: To perform a prospective cohort study to determine whether there was a difference in body mass index (BMI) between patients with GERD and patients with Barrett's oesophagus (BE). METHODS: We prospectively enrolled patients undergoing endoscopic evaluation for GERD and collected information regarding BMI, tobacco and/or alcohol use, and family history of GERD. Patients with non-erosive reflux disease underwent confirmatory 24-h pH testing. RESULTS: Seven hundred and fifty one patients with GERD (mean +/- s.d. age of 55.4 +/- 14.2 years, 74% male) entered the study, and BE was present in 165 (22%, 90% male, 79% Caucasian) patients. The mean GERD symptom duration was 10.3 +/- 0.4 years (range 1-62 years) with a mean body mass index of 27.8 +/- 0.2 kg/m(2) (range 15-55) Compared with patients having GERD alone, patients with BE were more likely to be older (P = 0.001), male (P < 0.001), current or prior tobacco users (P = 0.002), and with greater duration of GERD symptoms (P < 0.001). There was no significant difference in the BMI for patients with and without BE. CONCLUSIONS: While obesity is a risk factor for both GERD and BMI, patients with BE did not demonstrate increased BMI compared with patients having chronic GERD.     

Identifying response to acid suppressive therapy in functional dyspepsia using a random starting day trial – is gastro‐oesophageal reflux important?

BACKGROUND: Single subject trials offer an alternative approach to identify and characterize responders to a specific treatment. AIM: To test a new single subject trials design, called random starting day trial, to identify acid-related symptoms in dyspepsia. METHODS: A total of 119 patients with functional dyspepsia entered a 12-day, double-blind random starting day trial. All patients started on placebo and switched to omeprazole 80 mg/day at a randomized and blinded day between day 5 and day 9, with active treatment continuing for the rest of the trial. Based on changes of a daily symptom score, response was defined as a sustained > or =50% reduction of symptoms within 3 days of active treatment. RESULTS: Thirteen of 119 patients (11%) were classified as spontaneous responders because of complete symptom relief before switching to omeprazole. Of the remaining 106 patients, 15 (15.6%) were classified as responders. Five of six (83%) responders compared with 28 of 53 (53%) non-responders had pathological reflux. Multivariate testing identified symptoms suggestive of gastro-oesophageal reflux predictive of response. CONCLUSIONS: The random starting day trial design could identify a subset of dyspeptic patients with a uniform symptomatic response to acid-suppressive therapy. Response seems to be associated with gastro-oesophageal reflux. The random starting day trial needs to be further validated to be considered as a reliable instrument in clinical research.     

Treatment of gastro‐oesophageal reflux disease with rabeprazole in primary and secondary care: does Helicobacter pylori infection affect proton pump inhibitor effectiveness?

BACKGROUND: The presence of the gastric pathogen, Helicobacter pylori influences acid suppression by proton pump inhibitors and treatment outcome in patients with gastro-oesophageal reflux disease. AIM: To determine the influence of H. pylori infection on effectiveness of rabeprazole in primary and secondary care patients with gastro-oesophageal reflux disease. METHODS: Patients from primary and secondary care centres with uninvestigated gastro-oesophageal reflux disease (based on symptoms only) and investigated gastro-oesophageal reflux disease (endoscopically confirmed oesophagitis or endoscopy-negative reflux disease) were tested for H. pylori and treated with rabeprazole 20 mg once daily for 4-8 weeks in a non-randomized, multicentre, open-label study. Primary end-point for treatment effectiveness was complete resolution of both heartburn and acid regurgitation at 4-8 weeks; secondary end-point was quality of life as registered with the Psychological General Well-being Index. RESULTS: Data of 1787 patients could be analysed; mean duration of treatment was 36.3 days. At the evaluation visit 76.9% were heartburn-free, 77.7% regurgitation-free and 71% had complete symptom resolution. Overall Psychological General Well-being Index scores improved accordingly. Treatment was equally effective in patients with or without H. pylori infection, but more effective in patients with oesophagitis when compared with symptomatic gastro-oesophageal reflux disease. CONCLUSIONS: The effectiveness of rabeprazole in gastro-oesophageal reflux disease is not affected by the presence of H. pylori infection.     

Endothelin and erectile dysfunction: a target for pharmacological intervention?

Although erectile dysfunction (ED) is not life threatening, this common problem can significantly affect the quality of life and psychological and social well-being. The Massachusetts male ageing study (1,290 men aged 40 - 70 years) showed that 52% of men reported some degree of ED (17.1% mild, 25.2% moderate, 9.6% total). In the UK, an estimated 17 - 19% of men are thought to suffer from ED. This problem is more common with advancing age and since this proportion of the population is increasing, the prevalence of ED is expected to rise. Endothelin-1 (ET-1) belongs to a family of potent vasoconstrictor peptides consisting of 21 amino acids. We review the evidence showing that ET-1 plays a role via (ET_A and ET_B receptors) in the regulation of cavernosal smooth muscle tone. We also consider the various risk factors that are involved in the pathogenesis of ED and how these relate to the action of ET-1. In particular, the role of diabetes, hypertension, smoking and dyslipidaemia are discussed. The pharmaceutical industry has declared an interest in the development of ET antagonists for use in the treatment of various diseases including ED. We briefly comment on experimental ET-1 antagonists that may be of therapeutic benefit in ED.     

Endothelin and erectile dysfunction: a target for pharmacological intervention?

Although erectile dysfunction (ED) is not life threatening, this common problem can significantly affect the quality of life and psychological and social well-being. The Massachusetts male ageing study (1,290 men aged 40 - 70 years) showed that 52% of men reported some degree of ED (17.1% mild, 25.2% moderate, 9.6% total). In the UK, an estimated 17 - 19% of men are thought to suffer from ED. This problem is more common with advancing age and since this proportion of the population is increasing, the prevalence of ED is expected to rise. Endothelin-1 (ET-1) belongs to a family of potent vasoconstrictor peptides consisting of 21 amino acids. We review the evidence showing that ET-1 plays a role via (ET(A) and ET(B) receptors) in the regulation of cavernosal smooth muscle tone. We also consider the various risk factors that are involved in the pathogenesis of ED and how these relate to the action of ET-1. In particular, the role of diabetes, hypertension, smoking and dyslipidaemia are discussed. The pharmaceutical industry has declared an interest in the development of ET antagonists for use in the treatment of various diseases including ED. We briefly comment on experimental ET-1 antagonists that may be of therapeutic benefit in ED.