International validation of a health-related quality of life questionnaire in patients with erosive gastro-oesophageal reflux disease.

BACKGROUND: Although erosive gastro-oesophageal reflux disease (GERD) is a highly prevalent condition, there is no specific, valid, reliable and sensitive questionnaire that allows evaluating treatment-induced changes in health-related quality of life (HRQoL). AIM: To design a self-administered questionnaire, the GERD Analyzer (GERDyzer), for use in clinical studies. METHODS: The GERDyzer comprises 10 dimensions each illustrated by pictogram-like drawings, simplifying communication with the patients. Self-assessment is performed by 100 mm Visual Analogue Scales. For validation, a 5-week clinical trial involving 395 patients (per-protocol) with oesophagitis was conducted. Patients were treated with pantoprazole (40 mg o.d.) for 28 days. Psychometric analyses included internal consistency, test-retest reliability, responsiveness and construct validity. RESULTS: Factor analysis showed consistency of the dimensions and no reduction was necessary. Validation of GERDyzer indicated high internal consistency (Cronbach's alpha = 0.95) and test-retest reliability (intraclass correlation coefficient =0.91). Responsiveness of the total score expressed by nonparametric effect size was 1.38. Comparison of scores with other questionnaires resulted in logical correlation levels depending on the respected concepts measured. Conclusions GERDyzer proved to be highly valid, reproducible and responsive. It allows reliably assessing treatment-induced changes in HRQoL in erosive GERD.

Clinical trial: intravenous pantoprazole vs. ranitidine for the prevention of peptic ulcer rebleeding: a multicentre, multinational, randomized trial.

BACKGROUND: Controlled pantoprazole data in peptic ulcer bleeding are few. AIM: To compare intravenous (IV) pantoprazole with IV ranitidine for bleeding ulcers. METHODS: After endoscopic haemostasis, 1256 patients were randomized to pantoprazole 80 mg+8 mg/h or ranitidine 50 mg+13 mg/h, both for 72 h. Patients underwent second-look endoscopy on day 3 or earlier, if clinically indicated. The primary endpoint was an overall outcome ordinal score: no rebleeding, rebleeding without/with subsequent haemostasis, surgery and mortality. The latter three events were also assessed separately and together. RESULTS: There were no between-group differences in overall outcome scores (pantoprazole vs. ranitidine: S0: 91.2 vs. 89.3%, S1: 1.5 vs. 2.5%, S2: 5.4 vs. 5.7%, S3: 1.7 vs. 2.1%, S4: 0.19 vs. 0.38%, P = 0.083), 72-h clinically detected rebleeding (2.9% [95% CI 1.7, 4.6] vs. 3.2% [95% CI 2.0, 4.9]), surgery (1.9% [95% CI 1.0, 3.4] vs. 2.1% [95% CI 1.1, 3.5]) or day-3 mortality (0.2% [95% CI 0, 0.09] vs. 0.3% [95% CI 0, 1.1]). Pantoprazole significantly decreased cumulative frequencies of events comprising the ordinal score in spurting lesions (13.9% [95% CI 6.6, 24.7] vs. 33.9% [95% CI 22.1, 47.4]; P = 0.01) and gastric ulcers (6.7% [95% CI 4, 10.4] vs. 14.3% [95% CI 10.3, 19.2], P = 0.006). CONCLUSIONS: Outcomes amongst pantoprazole and ranitidine-treated patients were similar; pantoprazole provided benefits in patients with arterial spurting and gastric ulcers.

Systematic review: health-related quality of life (HRQOL) questionnaires in gastro-oesophageal reflux disease.

BACKGROUND: Although gastro-oesophageal reflux disease (GERD) has a well-established pathophysiology, the impact of GERD symptoms on the patients' quality of life can be profound. Therefore, health-related quality of life (HRQOL) questionnaires have become standard instruments to evaluate the effect of treatment in clinical trials. AIM: To evaluate the reliability, validity and responsiveness of available GERD-specific HRQOL. METHODS: A systematic literature search using the Medical Subject Headings terms: 'Gastro-oesophageal reflux', 'Heartburn' and 'Oesophagitis' with 'quality of life' and 'questionnaires' was preformed to identify the available HRQOL questionnaires. To analyse the psychometric properties of the respective tools, the actual guidelines for the use of patient-reported outcomes in clinical trials were applied. RESULTS: We identified five GERD-specific HRQOL questionnaires but none of them fulfilled all quality criteria; either they did not meet the actual standards for psychometric properties (HBQOL, GERD-HRQL, Jasani et al.Aust Fam Physician 1999; 28: 515), or were impracticable to use in clinical trials. The generic and hybrid instruments lack specificity and sensitivity and were not designed for treatment evaluation in GERD patients. CONCLUSION: There is need for a new evaluative tool in the assessment of HRQOL during GERD therapy.

Validation of a brief symptom questionnaire (ReQuest in Practice) for patients with gastro-oesophageal reflux disease.

BACKGROUND: A clinical need exists for a means of assessing symptom control in patients with gastro-oesophageal reflux disease. The ReQuest questionnaire has been extensively validated for symptom assessment in both erosive and non-erosive gastro-oesophageal reflux disease but was designed for research purposes. We derived a shorter version (ReQuest in Practice) that would be more convenient for clinical practice. AIM: To validate ReQuest in Practice in patients suffering from gastro-oesophageal reflux disease. METHODS: Multicentre, non-interventional, crossover comparison. Patients completed ReQuest in Practice followed by ReQuest or vice versa. Before and after a planned endoscopy, patients completed the health-related quality of life questionnaire GERDyzer. Internal consistency and the Intraclass Correlation Coefficient were calculated. Construct validity was evaluated by correlation with ReQuest and GERDyzer. RESULTS: There was high internal consistency of ReQuest in Practice (Cronbach's alpha: 0.9) and a high Intraclass Correlation Coefficient of 0.99. The measurement error of ReQuest in Practice was 4.1. High correlation between ReQuest in Practice and ReQuest (Spearman correlation coefficient: 0.9) and GERDyzer (Spearman correlation coefficient: 0.8) demonstrated construct validity. CONCLUSIONS: ReQuest in Practice was proven to be valid and reliable. Its close correlation with ReQuest makes it a promising tool to guide the clinical management of patients across the full spectrum of both erosive and non-erosive gastro-oesophageal reflux disease.

Intranasal trigeminal sensitivity in subjects with allergic rhinitis.

Trigeminal nerve endings of the human nasal mucosa are activated by chemical, physical or thermal stimuli. Activation of these A(delta) and C fibers can be quantified through the recording of chemo-somatosensory event-related potentials (ERP). The aim of this study was to investigate whether allergy-related activation of trigeminal nerve endings leads to changes in their responsiveness to intranasal trigeminal stimulation. Gaseous carbon dioxide (CO(2)) stimuli were applied in three sessions (baseline, after NaCl solution and after allergen application) to the nasal mucosa of 13 subjects with allergic rhinitis. Chemo-somatosensory ERP were recorded, and subjects rated the intensity of rhinitis symptoms. Administration of allergen produced a significant shortening of chemo-somatosensory ERP peak latencies P1 and N1. Observed changes of latencies were in line with rhinitis symptoms subjects indicated during the session. In addition, there was a negative relation between the general symptom score and ERP peak latencies, obtained both at baseline and after allergen exposure. In conclusion, it is hypothesized that in patients suffering from allergic rhinitis, nasal itching and sneezing after allergen exposure are, at least in part, clinical correlates of the activation of trigeminal nerve endings due to local inflammatory mechanisms. The correlations between ERP latencies and the patients' symptoms indicate that ERP latencies may possess a predictive value of the subjects' responsiveness to allergens.