Implications for treatment: pH, Helicobacter pylori or alternative approaches?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74597/1/j.1365-2036.2004.02351.x.pd

Uninvestigated dyspepsia and non-ulcer dyspepsia—the use of endoscopy and the roles of Helicobacter pylori eradication and antisecretory therapy

Due to its prevalence, impact on quality-of-life and the associated significant health resource utilization, dyspepsia is a major healthcare concern. The available management strategies for uninvestigated dyspepsia include prompt endoscopy, the ‘test-and-treat’ strategy for Helicobacter pylori , and empiric antisecretory therapy. There is consensus that endoscopy should be reserved for patients with alarm features (e.g. symptom onset after 45 years of age, recurrent vomiting, weight loss, dysphagia, evidence of bleeding, anaemia), H. pylori -positive individuals who fail test-and-treat, and those with an inadequate response to empiric antisecretory therapy. Factors influencing the decision between test-and-treat and empiric antisecretory therapy in uninvestigated dyspepsia include the local prevalence of H. pylori and peptic ulcer disease and the proportion of ulcers attributable to H. pylori . For uninvestigated dyspepsia in patients without alarm features, test-and-treat is the preferred initial management method in Europe based on the relatively high prevalence of H. pylori /peptic ulcer disease whereas empiric antisecretory therapy is preferred in many parts of the United States, where the prevalence of H. pylori /peptic ulcer disease is relatively low. In patients with non-ulcer dyspepsia, H. pylori eradication and empiric antisecretory therapy result in comparable and small, but statistically significant, improvements in dyspepsia. Empiric antisecretory therapy is the preferred initial method of managing non-ulcer dyspepsia in Europe and the US. The test-and-treat approach would receive increased enthusiasm if H. pylori cure is shown to prevent development of gastric cancer in non-ulcer dyspepsia patients in a large Western trial.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72556/1/j.0953-0673.2004.01829.x.pd

Functional Dyspepsia

Dyspepsia is a constellation of symptoms referable to the gastroduodenal region of the upper gastrointestinal tract. Functional dyspepsia, a relapsing and remitting disorder, is the most common cause of these symptoms. The current standard for the diagnosis of functional dyspepsia is the Rome III criteria, developed by the Rome III Committees, a multinational group of experts in the field, first convened in 1990, that meets regularly to review and revise the diagnostic criteria for all functional gastrointestinal disorders. In most patients with functional dyspepsia, the natural history is chronic and fluctuating, with periods of time when the patient is asymptomatic followed by episodes of symptom relapse. Data from population-based studies suggest that, during extended follow-up, approximately 15 to 20% of people with functional dyspepsia have persistent symptoms and 50% have resolution of symptoms; in the remaining 30 to 35% of patients symptoms will fluctuate and meet the criteria for another functional gastrointestinal disorder.81 Despite the chronic nature of functional dyspepsia, there is no evidence to suggest that it is associated with decreased survival

Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials

OBJECTIVES: To determine whether searching for Helicobacter pylori and treating with eradication therapy leads to a reduction in incidence of gastric cancer among healthy asymptomatic infected individuals. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, and the Cochrane central register of controlled trials were searched through to December 2013. Conference proceedings between 2001 and 2013 were hand searched. A recursive search was performed with bibliographies of relevant studies. There were no language restrictions. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials examining the effect of at least seven days of eradication therapy on subsequent occurrence of gastric cancer in adults who tested positive for Helicobacter pylori but otherwise healthy and asymptomatic were eligible. The control arm had to receive placebo or no treatment. Subjects had to be followed for ≥ 2 years. MAIN OUTCOME MEASURES: Primary outcome, defined a priori, was the effect of eradication therapy on the subsequent occurrence of gastric cancer expressed as a relative risk of gastric cancer with 95% confidence intervals. RESULTS: The search strategy identified 1560 citations, of which six individual randomised controlled trials were eligible. Fifty one (1.6%) gastric cancers occurred among 3294 individuals who received eradication therapy versus 76 (2.4%) in 3203 control subjects (relative risk 0.66, 95% confidence interval 0.46 to 0.95), with no heterogeneity between studies (I(2)=0%, P=0.60). If the benefit of eradication therapy was assumed to persist lifelong the number needed to treat was as low as 15 for Chinese men and as high as 245 for US women. CONCLUSIONS: These data provide limited, moderate quality evidence that searching for and eradicating H pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but these data cannot necessarily be extrapolated to other populations

5G RAN/MEC Slicing and Admission Control using Deep Reinforcement Learning

The 5G RAN functions can be virtualized and distributed across the radio unit (RU), distributed unit (DU), and centralized unit (CU) to facilitate flexible resource management. Complemented by multi-access edge computing (MEC), these components create network slices tailored for applications with diverse quality of service (QoS) requirements. However, as the requests for various slices arrive dynamically over time and the network resources are limited, it is non-trivial for an infrastructure provider (InP) to optimize its long-term revenue from real-time admission and embedding of slice requests. Prior works have leveraged Deep Reinforcement Learning (DRL) to address this problem, however, these solutions either do not scale to realistic topologies, require re-training of the DRL agents when facing topology changes, or do not consider the slice admission and embedding problems jointly. In this thesis, we use multi-agent DRL and Graph Attention Networks (GATs) to address these limitations. Specifically, we propose novel topology-independent admission and slicing agents that are scalable and generalizable to large and different metropolitan networks. Results show that the proposed approach converges faster and achieves up to 35.2% and 20% gain in revenue compared to heuristics and other DRL-based approaches, respectively. Additionally, we demonstrate that our approach is generalizable to scenarios and substrate networks previously unseen during training, as it maintains superior performance without re-training or re-tuning. Finally, we extract the attention maps of the GAT, and analyze them to detect potential bottlenecks and efficiently improve network performance and InP revenue through eliminating them

Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive people

BACKGROUND: Peptic ulcer disease is the cause of dyspepsia in about 10% of people. Ninety-five percent of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H. pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain. This is an update of Ford AC, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive patients. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003840. DOI: 10.1002/14651858.CD003840.pub4. OBJECTIVES: To assess the proportion of peptic ulcers healed and the proportion of participants who remained free from relapse with eradication therapy against placebo or other pharmacological therapies in H. pylori-positive people.To assess the proportion of participants that achieved complete relief of symptoms and improvement in quality of life scores.To compare the incidence of adverse effects/drop-outs (total number for each drug) associated with the different treatments.To assess the proportion of participants in whom successful eradication was achieved. SEARCH METHODS: In this update, we identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (1950 to March 2016) and Ovid EMBASE (1980 to March 2016). To identify further relevant trials, we handsearched reference lists from trials selected by electronic searching, and published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology). The search was last updated in March 2016. We contacted members of Cochrane Upper GI and Pancreatic Diseases, and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. SELECTION CRITERIA: We analysed randomised controlled trials of short- and long-term treatment of peptic ulcer disease in H. pylori-positive adults. Participants received at least one week of H. pylori eradication compared with ulcer healing drug, placebo or no treatment. Trials were included if they reported assessment from two weeks onwards. DATA COLLECTION AND ANALYSIS: We collected data on ulcer healing, recurrence, relief of symptoms and adverse effects. We calculated the risk ratio (RR) with 95% confidence intervals (CI) using both fixed-effect and random-effects models with Review Manager software (RevMan 5.3) based on intention-to-treat analysis as far as possible. MAIN RESULTS: A total of 55 trials were included for one or more outcomes for this review.In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 participants, RR of ulcer persisting = 0.66, 95% confidence interval (CI) 0.58 to 0.76; 381/2286 (adjusted proportion: 12.4%) in eradication therapy plus UHD versus 304/1624 (18.7%) in UHD; low quality evidence) and no treatment (two trials, 207 participants, RR 0.37, 95% CI 0.26 to 0.53; 30/125 (adjusted proportion: 21.7%) in eradication therapy versus 48/82 (58.5%) in no treatment; low quality evidence).In gastric ulcer healing, the differences were imprecise between eradication therapy and UHD (15 trials, 1974 participants, RR 1.23, 95% CI 0.90 to 1.68; 220/1192 (adjusted proportion: 16.0%) in eradication therapy plus UHD versus 102/782 (13.0%) in UHD; very low quality evidence). In preventing duodenal ulcer recurrence the differences were imprecise between maintenance therapy with H.pylori eradication therapy and maintenance therapy with UHD (four trials, 319 participants, RR of ulcer recurring 0.73; 95% CI 0.42 to 1.25; 19/159 (adjusted proportion: 11.9%) in eradication therapy versus 26/160 (16.3%) in UHD; very low quality evidence), but eradication therapy was superior to no treatment (27 trials 2509 participants, RR 0.20, 95% CI 0.15 to 0.26; 215/1501 (adjusted proportion: 12.9%) in eradication therapy versus 649/1008 (64.4%) in no treatment; very low quality evidence).In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (12 trials, 1476 participants, RR 0.31, 95% CI 0.22 to 0.45; 116/697 (adjusted proportion: 16.3%) in eradication therapy versus 356/679 (52.4%) in no treatment; very low quality evidence). None of the trials reported proportion of people with gastric ulcer not healed after initial therapy between H.pylori eradication therapy and no active treatment or the proportion of people with recurrent gastric ulcer or peptic ulcers during maintenance therapy between H.pylori eradication therapy and ulcer healing drug therapy. AUTHORS' CONCLUSIONS: Adding a one to two-week course of H. pylori eradication therapy is an effective treatment for people with H. pylori-positive duodenal ulcer when compared to ulcer healing drugs alone and no treatment. H. pylori eradication therapy is also effective in preventing recurrence of duodenal and gastric ulcer compared to no treatment. There is currently no evidence that H. pylori eradication therapy is an effective treatment in people with gastric ulcer or that it is effective in preventing recurrence of duodenal ulcer compared to ulcer healing drug. However, confidence intervals were wide and significant benefits or harms of H. pylori eradication therapy in acute ulcer healing of gastric ulcers compared to no treatment, and in preventing recurrence of duodenal ulcers compared to ulcer healing drugs cannot be ruled out

Extension Ability of Reduced Order Model of Unsteady Incompressible Flows Using a Combination of POD and Fourier Modes

In this article, an improved reduced order modelling approach, based on the proper orthogonal decomposition (POD) method, is presented. After projecting the governing equations of flow dynamics along the POD modes, a dynamical system was obtained. Normally, the classical reduced order models do not predict accurate time variations of flow variables due to some reasons. The response of the dynamical system was improved using a calibration method based on a least-square optimization process. The calibration polynomial can be assumed as the pressure correction term which is vanished in projecting the Navier-Stokes equations along the POD modes. The above least- square procedure is a combination of POD method and the solution of an optimization problem. The obtained model can predict accurate time variations of flow field with high speed. For long time periods, the calibration term can be computed using a combined form of POD and Fourier modes. This extension is a totally new extension to this procedure which has recently been proposed by the authors. The results obtained from the calibrated reduced order model show close agreements to the benchmark DNS data, proving high accuracy of our model