Multicentre prospective study to evaluate effectiveness and safety of gel-forming and hyaluronic-acid containing chewable tablets as add-on treatment in patients with gastroesophageal reflux disease (GERD) symptoms and unsatisfying proton pump inhibitor therapy.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common disease which in the majority of patients is treated with proton pump inhibitors (PPI). However, up to 45% of the patients remain symptomatic on a standard dose of PPI. This study investigated the effectiveness and safety of an add-on therapy with the gel-forming chewable tablet Sobrade® in patients unsatisfied with PPI treatment. The bioadhesive gel covers the oesophagus and thereby protects the mucosa from reflux events. METHODS: 47 patients with symptomatic GERD despite PPI treatment participated in this study. The gel-forming tablets were taken up to four times daily after meals and prior to bedtime. Severity and frequency of GERD symptoms were evaluated during two onsite visits prior and following 14 days of treatment and used to calculate the GERD score of the Reflux Disease Questionnaire. Furthermore, patients recorded symptoms as well as onset and duration of symptoms relief daily in their electronic dairies. Effectiveness of treatment was analysed using non-parametric paired Wilcoxon test. In addition, anchor-based minimal important differences (MID) were assessed. RESULTS: Treatment resulted in significant reduction of GERD symptoms. Severity and frequency of 8 of the 9 assessed symptoms improved significantly during the treatment phase whereby most pronounced improvement was observed for heartburn. In agreement, all three subscales of the GERD score improved significantly. MID results suggest that patients considered a mean improvement of symptoms > 30% of initial severity as beneficial. Self-assessments by patients revealed first significant improvements of symptoms like heartburn and regurgitation from day 5 of treatment onwards. 49% of patients reported relief of symptoms within 15 min which lasted on average for 3.5 h. During the study no treatment emergent adverse events were reported and in 98% of all cases tolerability of the product was rated as very good or good. CONCLUSIONS: This study revealed a pronounced improvement of the symptoms after add-on treatment with the gel-forming medical device. The very good safety and tolerability profile indicate an advantageous risk-benefit ratio. TRIAL REGISTRATION: This non-interventional study was prospectively positively evaluated by the responsible ethic-committees.

Chance-level hit rates in closed-set, forced-choice audiometry and a novel utility for the significance test-based detection of malingering.

The primary aim of this study was to extend existing theory on the relationship between chance-level performance and the number of alternatives and trials in closed-set, forced-choice speech audiometry and sound localization methods. When calculating chance performance for closed-set, forced-choice experiments with multiple trials, the binomial distribution should be preferred over the simple 1/a probability, as the latter is appropriate only for single trial experiments. The historical use of constant hit rates for determining chance performance has been based upon the assumption that random hits are distributed evenly across multiple trials. For any closed-set, forced-choice task with 2 to 10 alternatives and 2 to 100 trials, we calculated the probability of obtaining any given hit rate due to random guessing alone according to the binomial distribution. Hit rates with probabilities p > 0.05 were interpreted as being likely to occur due to random chance alone, whereas hit rates with probabilities of p ≤ 0.05 were interpreted as being unlikely to occur due to chance alone. For sound localization experiments with speakers at fixed positions, the expected probability of a random hit was also calculated using the binomial distribution. The expected angular root mean square (rms) error in sound localization resulting from the random selection of sound sources was investigated using Monte Carlo simulations. A new aspect in the interpretation of test results was identified for situations in which the observed number of hits is much lower than would be expected due to chance alone. For test methods incorporating a relatively low number of alternatives and a sufficiently high, yet clinically feasible, number of trials, both upper and lower thresholds for chance-level performance could be identified. This lower threshold represents the lowest hit rate which can be expected through random chance alone. Extending interpretation of results to include this lower threshold affords the ability to not only identify performance significantly superior to that of chance, but also that significantly poorer than chance and thereby represents a simple method for the objective detection of malingering.