Rolf Carlsson

Initial validation of a diagnostic questionnaire for gastroesophageal reflux disease

OBJECTIVES:Brief, reliable, and valid self-administered questionnaires could facilitate the diagnosis of gastroesophageal reflux disease in primary care. We report the development and validation of such an instrument.METHODS:Content validity was informed by literature review, expert opinion, and cognitive interviewing of 50 patients resulting in a 22-item survey. For psychometric analyses, primary care patients completed the new questionnaire at enrollment and at intervals ranging from 3 days to 3 wk. Multitrait scaling, test–retest reliability, and responsiveness were assessed. Predictive validity analyses of all scales and items used specialty physician diagnosis as the “gold standard.”RESULTS:Iterative factor analyses yielded three scales of four items each including heartburn, acid regurgitation, and dyspepsia. Multitrait scaling criteria including internal consistency, item interval consistency, and item discrimination were 100% satisfied. Test–retest reliability was high in those reporting stable symptoms. Scale scores significantly changed in those reporting a global change. Regressing specialty physician diagnosis on the three scales revealed significant effects for two scales (heartburn and regurgitation). Combining the two significant scales enhanced the strength of the model. Symptom response to self-directed treatment with nonprescription antisecretory medications was highly predictive of the diagnosis also, although the item demonstrated poor validity and reliability.CONCLUSIONS:A brief, simple 12-item questionnaire demonstrated validity and reliability and seemed to be responsive to change for reflux and dyspeptic symptoms.

Esomeprazole 40 mg and 20 mg is efficacious in the long-term management of patients with endoscopy-negative gastro-oesophageal reflux disease: a placebo-controlled trial of on-demand therapy for 6 months

Background On-demand therapy may offer an effective approach to the long-term management of gastro-oesophageal reflux disease (GORD) without oesophagitis. Aim To examine the efficacy of the novel proton pump inhibitor esomeprazole as on-demand therapy in endoscopy-negative GORD. Patients and methods Endoscopy-negative GORD patients who achieved complete resolution of heartburn after short-term esomeprazole or omeprazole treatment (n = 721) were randomized to esomeprazole 20 mg (n = 282), 40 mg (n = 293) or placebo (n = 146) on demand (maximum one dose/day) for 6 months. The primary and secondary efficacy endpoints were time to study discontinuation due to (i) unwillingness to continue and (ii) inadequate control of heartburn, respectively. Results Both doses of esomeprazole were more effective than placebo. During the 6-month period, 42% of placebo recipients discontinued treatment due to unwillingness to continue, compared with 8% and 11% of esomeprazole 20 mg and 40 mg recipients, respectively. Overall, more patients treated with esomeprazole were free from gastrointestinal symptoms after 6 months of on-demand therapy. Conclusions Esomeprazole 20 mg was superior to placebo for on-demand treatment of GORD; a higher dose did not confer additional clinical benefit. Over 90% of patients were willing to continue on-demand treatment with esomeprazole 20 mg over a 6-month period.

Valid symptom reporting at upper endoscopy in a random sample of the Swedish adult general population: the Kalixanda study.

Background: Upper oesophagogastroduodenoscopy is considered to be the gold standard for upper gastrointestinal disease assessment, but is currently seldom used in epidemiological studies. One concern is that the procedure may bias sampling among volunteers in a general adult population. The aim of this study was to explore whether the procedure affects symptom reporting. Methods: A random sample of 3000 adults aged 20-81 years (mean age 50.4), from two Swedish municipalities (n = 21,610) was surveyed using a validated postal questionnaire (the Abdominal Symptom Questionnaire) assessing gastrointestinal symptoms. A subsample of the responders was invited, in random order, to undergo an upper endoscopy and repeated symptom reporting using the same questionnaire, as well as a serology test for Helicobacter pylori. Results: The response rate to the initial questionnaire was 74.2% and the participation rate for those eligible for the upper endoscopy was 73.3% (n = 1001, mean age 54.0 years, 48.8% male). No major social or symptom sampling error was encountered from the selection process, with the exception of an excess of symptom reporters among the youngest subjects. The prevalence of reflux symptoms, dyspeptic symptoms and irritable bowel symptoms was 40%, 37.6% and 29.6%, respectively, which is relatively high, but in no way extreme. Conclusions: The upper endoscopy survey strategy was successful. The response rate was high and there was no major selection bias of clinical relevance. The cohort selected for this study appears to be representative of the general Swedish adult population.

Is the esophageal squamous epithelial barrier function impaired in patients with gastroesophageal reflux disease

BACKGROUND A disturbed epithelial barrier function has been promoted as one factor in the pathogenesis of gastroesophageal reflux disease (GERD). We therefore studied the effect of acid perfusion on the transmural potential difference (PD) of the distal esophagus in relation to onset of reflux symptoms. METHODS PD was assessed during perfusion with saline and with 0.1 M HCl in healthy controls (n = 17) and in GERD patients without (n = 15) or with esophagitis (n = 6) and in remission after a fundoplication (n = 10). Heartburn and other upper GI symptoms were recorded concomitantly. Endoscopy-negative patients were studied before and after omeprazole treatment. RESULTS HCl perfusion induced more lumennegative peak PD values in patients with active GERD, regardless of the presence or absence of esophagitis, than in healthy controls. After successful therapy, the PD response to acid perfusion equalled that of healthy subjects. Acid perfusion was associated with the onset of heartburn in most patients with active GERD but in none of the healthy subjects, and less frequently after medical and surgical therapy. CONCLUSIONS The epithelial permeability to hydrogen ions differs between healthy subjects and patients with active GERD. Effective treatment, such as omeprazole or fundoplication, might improve the barrier function.

Psychological factors as a predictor of treatment response in patients with heartburn: A pooled analysis of clinical trials

Objective. A pooled analysis, using data from three prospective, randomized, double-blind, placebo-controlled, clinical studies, was undertaken to determine the relationship between well-being and subsequent clinical response to acid suppressant therapy in 1887 adult patients with reflux symptoms (with/without endoscopically verified erosive esophagitis). Material and methods. Well-being was assessed at study entry using the Psychological General Well-Being (PGWB) Index. Patients were assessed for complete relief of heartburn (absence of symptoms in the preceding 7 days) after 4 weeks’ treatment (omeprazole 10 or 20 mg once daily; ranitidine 150 mg twice daily). Results. Multiple logistic regression analysis identified baseline PGWB Index total score and anxiety score as independent prognostic indicators of treatment response in endoscopy-positive patients (n=1333). Thus, the likelihood of achieving complete heartburn relief was impaired by high baseline levels of anxiety or a low total well-being score. In the endoscopy-negative group, high levels of depression and low vitality scores affected treatment response adversely. Furthermore, age (for endoscopy-positive patients only) and body mass index (for endoscopy-negative patients only) showed an association with treatment outcome. Gender seemed to have no prognostic value on treatment outcome. Conclusions. Patient well-being may be a useful prognostic indicator in patients presenting with reflux symptoms, with a high level of anxiety predicating against a response to acid suppressant therapy, particularly in those with normal endoscopic findings.

Sufficient control of heartburn in endoscopy‐negative gastro‐oesophageal reflux disease trials

More than half the number of patients who report troublesome heartburn symptoms suggestive of gastro-oesophageal reflux disease (GORD) to their doctor present with no obvious oesophageal lesions at endoscopy (1–3). They do require medical therapy, however, and the objective of treatment in this endoscopy-negative group is symptom improvement and relief to a level where the symptoms are perceived as being under control. In clinical trials, the therapeutic response to treatment is usually assessed by asking patients to define the frequency and severity of their heartburn symptoms. While this may give reasonably accurate information about a very subjective outcome measure, it fails to address the question as to whether the patients perceive that they experienced sufficient heartburn control from their therapy, which is the aim of treatment in clinical practice. This analysis of data from a clinical trial relates preand post-treatment heartburn assessments to a standardized question to the patient: ‘Does the study medication give sufficient control of your heartburn?’ This relationship may guide the choice of a clinically relevant efficacy measure based on heartburn severity and frequency.

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.

Resolution of H. pylori antrum, corpus or pan-gastritis does not induced heartburn in patients with functional dyspepsia

Resolution of H-pylori antrum, corpus or pan-gastritis does not induce heartburn in patients with functional dyspepsia

Gastrointestinal (GI) symptoms, quality of life and endoscopic diagnoses in patients with upper GI symptoms

Gastrointestinal (GI) symptoms, quality of life and endoscopic diagnoses in patients with upper GI symptoms