Relationship between esomeprazole dose and timing to heartburn resolution in selected patients with gastroesophageal reflux disease

Roy C Orlando1, Sherry Liu2, Marta Illueca31Department of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA, 2Department of Statistics and Informatics, 3Department of Clinical Development, AstraZeneca LP, Wilmington, DE, USAObjective: To increase response rates to therapy by increasing the dosage of proton pump inhibitor (PPI) therapy in patients with gastroesophageal reflux disease (GERD) whose symptoms are predominantly associated with acid reflux.Methods: In this double-blind, randomized, proof-of-concept study, 369 patients with GERD and moderate heartburn lasting ≥three days/week, a history of response to antacids/acid suppression therapy, and a positive esophageal acid perfusion test result were randomized to esomeprazole 20 or 40 mg once daily, or to 40 mg twice daily for four weeks. Heartburn symptom relief/resolution was subsequently evaluated.Results: In this study population, no relationship was apparent between esomeprazole dosage and efficacy variables for sustained heartburn resolution (seven days without symptoms) at week 4 (48.0%, 44.0%, and 41.4% for esomeprazole 20 mg once daily, 40 mg once daily, and 40 mg twice daily, respectively). Nocturnal heartburn resolution with esomeprazole 40 mg twice daily showed a numeric improvement trend versus esomeprazole 20 and 40 mg once daily, but this was not statistically significant.Conclusions: Heartburn resolution rates at four weeks were similar for all esomeprazole dosages and comparable with rates reported previously, suggesting a plateau effect in terms of clinical response to acid suppression with PPI therapy in this population of selected GERD patients.Keywords: acid suppressive therapy, GERD, proton pump inhibito

Effects of esomeprazole treatment for gastroesophageal reflux disease on quality of life in 12- to 17-year-old adolescents: an international health outcomes study

<p>Abstract</p> <p>Background</p> <p>Although gastroesophageal reflux disease (GERD) is common in adolescents, the burden of GERD on health-related quality of life (HRQOL) in adolescents has not been previously evaluated. Therefore, the objective of the study was to examine the effect of GERD on HRQOL in adolescents.</p> <p>Methods</p> <p>This international, 31-site, 8-week safety study randomized adolescents, aged 12 to 17 years inclusive, with GERD to receive esomeprazole 20 or 40 mg once daily. The Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD), previously validated in adults, consists of 25 questions grouped into 5 domains: emotional distress, sleep disturbance, food/drink problems, physical/social functioning, and vitality. The QOLRAD was administered at the baseline and week-8 (final) visits.</p> <p>Results</p> <p>Of the 149 patients randomized, 134 completed the QOLRAD at baseline and final visits and were eligible for analysis of their HRQOL data. Baseline QOLRAD scores indicated GERD had a negative effect on the HRQOL of these adolescents, especially in the domains of vitality and emotional distress, and problems with food/drink. At the final visit, mean scores for all 5 QOLRAD domains improved significantly (<it>P </it>< .0001); change of scores (ie, delta) for all domains met or exceeded the adult QOLRAD minimal clinically significant difference standard of 0.5 units.</p> <p>Conclusion</p> <p>GERD had a negative effect on QOL in adolescents. After esomeprazole treatment, statistically and clinically significant improvements occurred in all domains of the QOLRAD for these adolescents.</p> <p>Trial Registration</p> <p>D9614C00098; ClinicalTrials.gov Identifier NCT00241501</p

Esomeprazole for the treatment of erosive esophagitis in children: an international, multicenter, randomized, parallel-group, double-blind (for dose) study

<p>Abstract</p> <p>Background</p> <p>Acid suppression with a proton pump inhibitor is standard treatment for gastroesophageal reflux disease and erosive esophagitis in adults and increasingly is becoming first-line therapy for children aged 1-17 years. We evaluated endoscopic healing of erosive esophagitis with esomeprazole in young children with gastroesophageal reflux disease and described esophageal histology.</p> <p>Methods</p> <p>Children aged 1-11 years with endoscopically or histologically confirmed gastroesophageal reflux disease were randomized to esomeprazole 5 or 10 mg daily (< 20 kg) or 10 or 20 mg daily (≥ 20 kg) for 8 weeks. Patients with erosive esophagitis underwent an endoscopy after 8 weeks to assess healing of erosions.</p> <p>Results</p> <p>Of 109 patients, 49% had erosive esophagitis and 51% had histologic evidence of reflux esophagitis without erosive esophagitis. Of the 45 patients who had erosive esophagitis and underwent follow-up endoscopy, 89% experienced erosion resolution. Dilation of intercellular space was reported in 24% of patients with histologic examination.</p> <p>Conclusions</p> <p>Esomeprazole (0.2-1.0 mg/kg) effectively heals macroscopic and microscopic erosive esophagitis in this pediatric population with gastroesophageal reflux disease. Dilation of intercellular space may be an important histologic marker of erosive esophagitis in children.</p> <p>Trial Registration</p> <p>D9614C00097; ClinicalTrials.gov identifier NCT00228527.</p

Scale corrections for faster evaluation of convergent Fresnel patterns

Numerical calculation of Fresnel patterns through fast Fourier transforms usually requires an extremely large number of samples in order to fulfil the Nyquist sampling condition. In many applications, the cut-off frequency of the system is much below the limit fixed by our calculations. As a consequence of this, correct sampling may result in heavy processes that produce results of useless accuracy. Unfortunately, subsampling may introduce aliasing that may distort the final appearance of the diffracted pattern. In this paper, we present a simple method that permits subsampling the Fresnel pattern while maintaining the Nyquist condition, and thus preventing the appearance of aliasing effects in the calculation. Secondary effects of the subsamplings are rescaling the illuminating wavelength and the introduction of an effective low-pass filter. Some applications relative to the propagation of the light inside the human eye are also suggested in the text.This work has been supported by the Conselleria de Empresa, Universitat i Ciència of the Generalitat Valenciana, through project GV04A/578

Retinal image quality assessment through a visual similarity index

Retinal image quality is commonly analyzed through parameters inherited from instrumental optics. These parameters are defined for ‘good optics’ so they are hard to translate into visual quality metrics. Instead of using point or artificial functions, we propose a quality index that takes into account properties of natural images. These images usually show strong local correlations that help to interpret the image. Our aim is to derive an objective index that quantifies the quality of vision by taking into account the local structure of the scene, instead of focusing on a particular aberration. As we show, this index highly correlates with visual acuity and allows inter-comparison of natural images around the retina. The usefulness of the index is proven through the analysis of real eyes before and after undergoing corneal surgery, which usually are hard to analyze with standard metrics.Financial support of the Generalitat Valenciana through the projects PROMETEO/2011/021 and ISIC/2012/013 and the University of Alicante through the project GRE10-09

Fourier analysis methodology of trabecular orientation measurement in the human tibial epiphysis

Methods to quantify trabecular orientation are crucial in order to assess the exact trajectory of trabeculae in anatomical and histological sections. Specific methods for evaluating trabecular orientation include the ‘point counting’ technique (Whitehouse, 1974), manual tracing of trabecular outlines on a digitising board (Whitehouse, 1980), textural analysis (Veenland et al. 1998), graphic representation of vectors (Shimizu et al. 1993; Kamibayashi et al. 1995) and both mathematical (Geraets, 1998) and fractal analysis (Millard et al. 1998). Optical and computer-assisted methods to detect trabecular orientation of bone using the Fourier transform were introduced by Oxnard (1982) later refined by Kuo & Carter (1991) (see also Oxnard, 1993, for a review), in the analysis of planar sections of vertebral bodies as well as in planar radiographs of cancellous bone in the distal radius (Wigderowitz et al. 1997). At present no studies have applied this technique to 2-D images or to the study of dried bones. We report a universal computer-automated technique for assessing the preferential orientation of the tibial subarticular trabeculae based on Fourier analysis, emphasis being placed on the search for improvements in accuracy over previous methods and applied to large stereoscopic (2-D) fields of anatomical sections of dried human tibiae. Previous studies on the trajectorial architecture of the tibial epiphysis (Takechi, 1977; Maquet, 1984) and research data about trabecular orientation (Kamibayashi et al. 1995) have not employed Fourier analysis

Eficiencia Visual de las lentes premontadas

Las gafas premontadas, dado su bajo coste económico, son ampliamente usadas por los pacientes présbitas como ayuda en visión de cerca. Estas lentes se fabrican en material orgánico y están montadas siguiendo unos parámetros estándar. Comparamos la calidad de visión obtenida con ellas y la que se obtiene con las lentes prescritas específicamente para un sujeto. Esta comparación se lleva a cabo evaluando la Función de la Sensibilidad al Contraste, la Agudeza Visual, la Función de Transferencia de Modulación y la Visión Binocular. Los resultados muestran una disminución de la calidad visual con las lentes premontadas en un porcentaje significativo de los casos, especialmente en el análisis de la binocularidad, donde se han obtenido importantes desviaciones en el horóptero longitudinal, lo que indica una posible aniseiconía inducida