Effects of pantoprazole 20 mg in mildgastroesophageal reflux disease: Once-daily treatment in the acute phase, and comparison of on-demand versus continuous treatment in the long term

AbstractBackground:Gastroesophageal reflux disease (GERD) is a chronic disorder,and although effective short-term treatment strategies are known, the rate of relapse within 1 year is as high as 90% despite successful acute treatment. Consequently, most patients with GERD require an effective long-term management strategy to achieve adequate symptom control and maintain mucosal healing.Objective:The present study was undertaken to compare the control ofGERD symptoms during long-term (24-week) treatment with pantoprazole 20 mg used on-demand or continuously in patients with mild GERD after complete relief of acute GERD symptoms.Methods:Patients with endoscopically confirmed Savary/Miller grade 0(normal mucosa) or I (patchy red lesions without white coating or with central white coating) GERD were enrolled in this multinational, multicenter study comprising 2 phases. In the first phase, which was open label, patients were treated with pantoprazole 20 mg QD for 4 weeks. The presence and intensity of the symptoms of heartburn, acid regurgitation, and pain on swallowing were assessed. In the second phase, which was an open-label, 24-week, randomized design, only patients completely free of GERD symptoms after acute treatment were included. During this phase, on-demand treatment with pantoprazole 20 mg was directly compared with continuous treatment. The rate of failure to control GERD symptoms after 24 weeks of treatment was estimated using the Kaplan-Meier method. Subsequently, the difference between treatments (on-demand minus continuous) and its 95% CI were calculated, and the on-demand treatment was tested for noninferiority using a predefined noninferiority margin of 20%. The mean daily symptom loads were compared between the treatment groups using the 1-sided Wilcoxon rank sum test on a 5% α level. The point estimate of the difference was determined using the Hodges-Lehman estimator and the 1-sided 95% CI according to Moses. The number of patients unwilling to continue due to insufficient control of heartburn, acid regurgitation, and pain on swallowing was analyzed using the Kaplan-Meier (time-to-event) analysis. Analysis was performed in the same manner as for the rate of failure to control GERD symptoms, but the 95% CI was interpreted for statistical superiority.Results:A total of 558 patients were enrolled in this study. At the end of theacute phase, 82.1% of patients in the per-protocol (PP) population and 79.1% in the intent-to-treat (ITT) population were relieved of all GERD symptoms, and subsequently entered the long-term phase. After 24 weeks of treatment, analysis of the failure rates revealed that on-demand treatment was noninferior to continuous treatment because the 95% CI was completely below 20% (ITT, 12.1% difference [95% CI, −∞ to 18.9%]; PP, 10.1% difference [95% CI, −∞ to 17.7%]). The higher perceived mean (SD) daily symptom load in the on-demand group (ITT, 1.26 [1.491 vs 0.82 [1.341) was balanced by the reduced tablet intake in that group (PP, 0.51 [0.31 ] vs 0.97 [0.11 ] tablets/d; P < 0.001). With respect to the rate of patients unwilling to continue treatment, no statistically significant difference was observed between the on-demand and continuous groups (ITT/PP, 0.95/1.13 vs 0.95/1.26).Conclusions:In this study of pantoprazole 20 mg tablets in patients withmild GERD, patients receiving on-demand treatment benefited despite their higher symptom load. The similar rates of unwillingness to continue treatment in both groups might suggest that patients were satisfied with the on-demand treatment strategy. On-demand treatment with pantoprazole 20 mg was found to be noninferior compared with continuous therapy with regard to symptom control. Both on-demand and continuous treatments were well tolerated

The impact of the AO foundation on fracture care : an evaluation of 60 years AO foundation

Objectives Sixty years ago, the Association of Osteosynthesis (AO) was founded with the aim to improve fracture treatment and has since grown into one of the largest medical associations worldwide. Aim of this study was to evaluate AO's impact on science, education, patient care and the MedTech business. Design/methods Impact evaluations were conducted as appropriate for the individual domains: Impact on science was measured by analyzing citation frequencies of publications promoted by AO. Impact on education was evaluated by analyzing the evolution of number and location of AO courses. Impact on patient care was evaluated with a health economic model analyzing cost changes and years of life gained through the introduction of osteosynthesis in 17 high-income countries (HICs). Impact on MedTech business was evaluated by analyzing sales data of AO-associated products. Results Thirty-five AO papers and 2 major AO textbooks are cited at remarkable frequencies in high ranking journals with up to 2000 citations/year. The number of AO courses steadily increased with a total of 645'000 participants, 20‘000 teaching days and 2‘500 volunteer faculty members so far. The introduction of osteosynthesis saved at least 925 billion Swiss Francs [CHF] in the 17 HICs analyzed and had an impact on avoiding premature deaths comparable to the use of antihypertensive drugs. AO-associated products generated sales of 55 billion CHF. Conclusion AO's impact on science, education, patient care, and the MedTech business was significant because AO addressed hitherto unmet needs by combining activities that mutually enriched and reinforced each other

Структура и свойства керамического композиционного материала ZrO[2](MgO)-MgO с бимодальной пористостью

In this paper, different implementations of elastic joint models of industrial robots are described and compared established in ADAMS and SimMechanics. The models are intended to be used for path prediction under process force load due to Roboforming and High Speed Cutting, respectively. The computational results have been compared and showed good agreement. In experiments of robot forming and robot milling the measured and simulated path deviations according to the process force are compared. The experiments are descriped and the results are discussed within the paper as a basis of a next step model based compensation of the path deviation

Ontology as Transcendental Philosophy

How does the critical Kant view ontology? There is no shared scholarly answer to this question. Norbert Hinske sees in the Critique of Pure Reason a “farewell to ontology,” albeit one that took Kant long to bid (Hinske 2009). Karl Ameriks has found evidence in Kant’s metaphysics lectures from the critical period that he “was unwilling to break away fully from traditional ontology” (Ameriks 1992: 272). Gualtiero Lorini argues that a decisive break with the tradition of ontology is essential to Kant’s critical reform of metaphysics, as is reflected in his shift from “ontology” to “transcendental philosophy,” two notions that Lorini takes to be related by mere “analogy” (Lorini 2015). I agree with Lorini that a thorough reform of ontology is a pivotal part of Kant’s critical plan for metaphysics and that ontology somehow “survives within the critical philosophy” (Lorini 2015: 76). To make this case, however, I deem it important to identify “ontology” and “transcendental philosophy” in the sense of extensional equivalence. While we can detect this identification in Kant’s writings, only from his metaphysics lectures can we get a full sense of its historical and philosophical significance. In this chapter I focus on how it represents a definitive turn from as well as notable continuity with traditional treatments of ontology, particularly the Wolffian one

A Guide to Ground in Kant's Lectures on Metaphysics

While scholars have extensively discussed Kant’s treatment of the Principle of Sufficient Ground in the Antinomies chapter of the Critique of Pure Reason, and, more recently, his relation to German rationalist debates about it, relatively little has been said about the exact notion of ground that figures in the PSG. My aim in this chapter is to explain Kant’s discussion of ground in the lectures and to relate it, where appropriate, to his published discussions of ground

Impact of osteosynthesis in fracture care : a cost comparison study

Aim: To estimate the health economic impact of osteosynthesis (OS) in fracture care over six decades in 17 high-income countries. Patients & methods: Applying a decision tree model, we assumed a hypothetical absence of OS and compared OS (intervention) with conservative treatment (CONS; comparator). We included patients with femur, tibia and radius fractures (age <65 years) and for proximal femur fractures also elderly patients (≥70 years). Results: We estimated savings in direct and indirect costs of 855 billion Swiss francs in the working age population in addition to 4.6 million years of life gained. In the elderly population, 69 billion Swiss francs were saved in direct costs of proximal femur fractures in addition to 73 million years of life gained. Conclusion: OS contributed to maximize health gains of society

Phylogeny and Classification of the Trapdoor Spider Genus Myrmekiaphila: An Integrative Approach to Evaluating Taxonomic Hypotheses

Background: Revised by Bond and Platnick in 2007, the trapdoor spider genus Myrmekiaphila comprises 11 species. Species delimitation and placement within one of three species groups was based on modifications of the male copulatory device. Because a phylogeny of the group was not available these species groups might not represent monophyletic lineages; species definitions likewise were untested hypotheses. The purpose of this study is to reconstruct the phylogeny of Myrmekiaphila species using molecular data to formally test the delimitation of species and species-groups. We seek to refine a set of established systematic hypotheses by integrating across molecular and morphological data sets. Methods and Findings: Phylogenetic analyses comprising Bayesian searches were conducted for a mtDNA matrix composed of contiguous 12S rRNA, tRNA-val, and 16S rRNA genes and a nuclear DNA matrix comprising the glutamyl and prolyl tRNA synthetase gene each consisting of 1348 and 481 bp, respectively. Separate analyses of the mitochondrial and nuclear genome data and a concatenated data set yield M. torreya and M. millerae paraphyletic with respect to M. coreyi and M. howelli and polyphyletic fluviatilis and foliata species groups. Conclusions: Despite the perception that molecular data present a solution to a crisis in taxonomy, studies like this demonstrate the efficacy of an approach that considers data from multiple sources. A DNA barcoding approach during the species discovery process would fail to recognize at least two species (M. coreyi and M. howelli) whereas a combine

Non-Invasive Imaging of Acute Renal Allograft Rejection in Rats Using Small Animal 18F-FDG-PET

BACKGROUND: At present, renal grafts are the most common solid organ transplants world-wide. Given the importance of renal transplantation and the limitation of available donor kidneys, detailed analysis of factors that affect transplant survival are important. Despite the introduction of new and effective immunosuppressive drugs, acute cellular graft rejection (AR) is still a major risk for graft survival. Nowadays, AR can only be definitively by renal biopsy. However, biopsies carry a risk of renal transplant injury and loss. Most important, they can not be performed in patients taking anticoagulant drugs. METHODOLOGY/PRINCIPAL FINDINGS: We present a non-invasive, entirely image-based method to assess AR in an allogeneic rat renal transplantation model using small animal positron emission tomography (PET) and (18)F-fluorodeoxyglucose (FDG). 3 h after i.v. injection of 30 MBq FDG into adult uni-nephrectomized, allogeneically transplanted rats, tissue radioactivity of renal parenchyma was assessed in vivo by a small animal PET-scanner (post operative day (POD) 1,2,4, and 7) and post mortem dissection. The mean radioactivity (cps/mm(3) tissue) as well as the percent injected dose (%ID) was compared between graft and native reference kidney. Results were confirmed by histological and autoradiographic analysis. Healthy rats, rats with acute CSA nephrotoxicity, with acute tubular necrosis, and syngeneically transplanted rats served as controls. FDG-uptake was significantly elevated only in allogeneic grafts from POD 1 on when compared to the native kidney (%ID graft POD 1: 0.54+/-0.06; POD 2: 0.58+/-0.12; POD 4: 0.81+/-0.06; POD 7: 0.77+/-0.1; CTR: 0.22+/-0.01, n = 3-28). Renal FDG-uptake in vivo correlated with the results obtained by micro-autoradiography and the degree of inflammatory infiltrates observed in histology. CONCLUSIONS/SIGNIFICANCE: We propose that graft FDG-PET imaging is a new option to non-invasively, specifically, early detect, and follow-up acute renal rejection. This method is potentially useful to improve post-transplant rejection monitoring

Rapid Enzymatic Response to Compensate UV Radiation in Copepods

Ultraviolet radiation (UVR) causes physical damage to DNA, carboxylation of proteins and peroxidation of lipids in copepod crustaceans, ubiquitous and abundant secondary producers in most aquatic ecosystems. Copepod adaptations for long duration exposures include changes in behaviour, changes in pigmentation and ultimately changes in morphology. Adaptations to short-term exposures are little studied. Here we show that short-duration exposure to UVR causes the freshwater calanoid copepod, Eudiaptomus gracilis, to rapidly activate production of enzymes that prevent widespread collateral peroxidation (glutathione S-transferase, GST), that regulate apoptosis cell death (Caspase-3, Casp-3), and that facilitate neurotransmissions (cholinesterase-ChE). None of these enzyme systems is alone sufficient, but they act in concert to reduce the stress level of the organism. The interplay among enzymatic responses provides useful information on how organisms respond to environmental stressors acting on short time scales

The pancreatic beta cell surface proteome

The pancreatic beta cell is responsible for maintaining normoglycaemia by secreting an appropriate amount of insulin according to blood glucose levels. The accurate sensing of the beta cell extracellular environment is therefore crucial to this endocrine function and is transmitted via its cell surface proteome. Various surface proteins that mediate or affect beta cell endocrine function have been identified, including growth factor and cytokine receptors, transporters, ion channels and proteases, attributing important roles to surface proteins in the adaptive behaviour of beta cells in response to acute and chronic environmental changes. However, the largely unknown composition of the beta cell surface proteome is likely to harbour yet more information about these mechanisms and provide novel points of therapeutic intervention and diagnostic tools. This article will provide an overview of the functional complexity of the beta cell surface proteome and selected surface proteins, outline the mechanisms by which their activity may be modulated, discuss the methods and challenges of comprehensively mapping and studying the beta cell surface proteome, and address the potential of this interesting subproteome for diagnostic and therapeutic applications in human disease