Impact of health insurance coverage forHelicobacter pylorigastritis on the trends in eradication therapy in Japan: retrospective observational study and simulation study based on real-world data

Objectives: To explore the prevalence of Helicobacter pylori infection in Japan and the trends of its eradication therapy before and after the changes of the insurance coverage policy, first started in 2000, and expanded to cover H. pylori-positive gastritis in 2013. The impacts that the changes brought were estimated. Methods: In this retrospective observational study and simulation study based on health insurance claims data, product sales data and relevant studies, individuals who received triple therapy (amoxicillin, clarithromycin, proton-pump inhibitors or potassium-competitive acid blockers) were defined as the first-time patients for H. pylori eradication in two Japanese health insurance claims databases (from approximately 1.6 million and 10.5 million individuals). Each sales data of eradication packages and examination kits were used to estimate the number of H. pylori-eradicated individuals nationwide. The prevalence of H. pylori infection, including the future rate, was predicted using previous studies and the estimated population trend by a national institute. Cases completed prior to the policy change on insurance coverage were simulated to estimate what would have happened had there been no change in the policy. Results: The numbers of patients first received eradication therapy were 81 119 and 170 993 from two databases. The nationwide estimated number of patients successfully eradicated was approximately 650 000 per year between 2001 and 2012, whereas it rapidly rose to 1 380-000 per year in 2013. The estimated prevalence of infection in 2050 is 5%, this rate was estimated to be 28% and 22% if the policy changes had not occurred in 2000 and 2013, respectively. Conclusions: The impact of policy changes for H. pylori eradication therapy on the prevalence of infection was shown. The results suggest that insurance coverage expansion may also reduce the prevalence in other countries with a high prevalence of H. pylori infection if the reinfection is low

Progastrin-like immunoreactivity in porcine antrum: Identification and characterization with region-specific antisera

In an effort to identify and characterize precursors of gastrin in tissues, we generated region-specific antisera against a synthetic progastrin peptide, Tyr-Gly-Trp-Met-Asp-Phe-Gly-Arg-Arg (GL9), as deduced from the nucleotide sequence of gastrin mRNA. This antisera did not cross-react with gastrin or progastrin peptides with shorter carboxyl-terminal extensions. Progastrin-like immunoreactivity (PGLI) was measured in porcine antrum at a concentration of 6.8 +/- 1.2 pmol/g wet weight (mean +/- SE, N = 5), or roughly 0.2% of that of gastrin. On Sephadex G50 chromatography, a major peak of PGLI was eluted as a slightly larger molecule than gastrin heptadecapeptide (G17) but possessed the same N-terminal immunoreactivity. These findings suggest that G17 may be formed by processing of a carboxyl-terminally extended precursor as an alternative to cleavage of big gastrin (G34).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25781/1/0000342.pd

Production of bioactive gastrin from the non-endocrine cell lines CHO and COS-7

AbstractWe made a mutated progastrin cDNA construct that contains a cleavage site (-Arg−4-Arg−3-Lys−2 -Arg−1) specific for the Kex2-like endoprotease furin, located ahead of the bioactive gastrin. For expressing the mutated progastrin cDNA, we used two non-endocrine cell lines, CHO and COS-7. CHO cells exhibit amidating enzyme activity and levels of amidation enzyme mRNA as high as those in the pituitary-derived endocrine cell line GH3, whereas COS-7 cells have far less amidating activity and lower amounts of mRNA. Mutant progastrin-expressing CHO cells produced mostly amidated gastrin. Gel filtration showed the size of this gastrin corresponded to that of the synthetic human gastrin-17. In contrast, COS-7 cells produced glycine-extended gastrin and only a small amount of amidated gastrin. The difference in the amount of amidated gastrin products produced by the two non-endocrine cell lines is due to differing amounts of the amidation enzyme contained in each cell line

Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study

Objective To assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use.Design A phase 3, 24-week, multicenter, randomised, double-blind (DB), active-controlled study, followed by a phase 3, ≥28 week, multicenter, single-blind, parallel-group extension study (EXT) in outpatients (n=642) receiving long-term NSAID therapy who are at risk of PU recurrence. The patients received vonoprazan (10 mg or 20 mg) or lansoprazole 15 mg once daily. For DB, non-inferiority of the proportion of patients with recurrent PU within 24 weeks was analysed by Farrington and Manning test (significance level 2.5%, non-inferiority margin 8.3%; primary endpoint), recurrent PU within 12 weeks, bleeding and time-to-event of PU (secondary endpoint) and treatment-emergent adverse events (TEAEs). For EXT, TEAEs (primary endpoint), recurrent PU and safety (secondary) were assessed up to 104 weeks for patients in the extension study.Results The non-inferiority of vonoprazan 10 mg and 20 mg to lansoprazole 15 mg was verified (percentage difference –2.2%,95% CI –6.2% to 1.8%, p<0.001; –2.1%,95% CI –6.1% to 2.0%, p<0.001, respectively). The proportion of patients with endoscopically confirmed recurrent PU within 24 weeks was 3.3%, 3.4% and 5.5%, for vonoprazan 10 mg, 20 mg and lansoprazole 15 mg, respectively. No significant safety concerns were identified.Conclusion The non-inferiority of vonoprazan (10 and 20 mg) was verified in patients receiving long-term NSAIDs in DB; it was effective and well tolerated in EXT for longer than 1 year, with a safety profile similar to lansoprazole (15 mg)

Comprehensive analysis of peptide-coding genes and initial characterization of an LRR-only microprotein in Marchantia polymorpha

In the past two decades, many plant peptides have been found to play crucial roles in various biological events by mediating cell-to-cell communications. However, a large number of small open reading frames (sORFs) or short genes capable of encoding peptides remain uncharacterized. In this study, we examined several candidate genes for peptides conserved between two model plants: Arabidopsis thaliana and Marchantia polymorpha. We examined their expression pattern in M. polymorpha and subcellular localization using a transient assay with Nicotiana benthamiana. We found that one candidate, MpSGF10B, was expressed in meristems, gemma cups, and male reproductive organs called antheridiophores. MpSGF10B has an N-terminal signal peptide followed by two leucine-rich repeat (LRR) domains and was secreted to the extracellular region in N. benthamiana and M. polymorpha. Compared with the wild type, two independent Mpsgf10b mutants had a slightly increased number of antheridiophores. It was revealed in gene ontology enrichment analysis that MpSGF10B was significantly co-expressed with genes related to cell cycle and development. These results suggest that MpSGF10B may be involved in the reproductive development of M. polymorpha. Our research should shed light on the unknown role of LRR-only proteins in land plants

Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding: An update 2018

Non-variceal upper gastrointestinal bleeding remains an important emergency condition, leading to significant morbidity and mortality. As endoscopic therapy is the 'gold standard' of management, treatment of these patients can be considered in three stages: pre-endoscopic treatment, endoscopic haemostasis and post-endoscopic management. Since publication of the Asia-Pacific consensus on non-variceal upper gastrointestinal bleeding (NVUGIB) 7 years ago, there have been significant advancements in the clinical management of patients in all three stages. These include pre-endoscopy risk stratification scores, blood and platelet transfusion, use of proton pump inhibitors; during endoscopy new haemostasis techniques (haemostatic powder spray and over-the-scope clips); and post-endoscopy management by second-look endoscopy and medication strategies. Emerging techniques, including capsule endoscopy and Doppler endoscopic probe in assessing adequacy of endoscopic therapy, and the pre-emptive use of angiographic embolisation, are attracting new attention. An emerging problem is the increasing use of dual antiplatelet agents and direct oral anticoagulants in patients with cardiac and cerebrovascular diseases. Guidelines on the discontinuation and then resumption of these agents in patients presenting with NVUGIB are very much needed. The Asia-Pacific Working Group examined recent evidence and recommends practical management guidelines in this updated consensus statement

AYUMS: an algorithm for completely automatic quantitation based on LC-MS/MS proteome data and its application to the analysis of signal transduction

BACKGROUND: Comprehensive description of the behavior of cellular components in a quantitative manner is essential for systematic understanding of biological events. Recent LC-MS/MS (tandem mass spectrometry coupled with liquid chromatography) technology, in combination with the SILAC (Stable Isotope Labeling by Amino acids in Cell culture) method, has enabled us to make relative quantitation at the proteome level. The recent report by Blagoev et al. (Nat. Biotechnol., 22, 1139–1145, 2004) indicated that this method was also applicable for the time-course analysis of cellular signaling events. Relative quatitation can easily be performed by calculating the ratio of peak intensities corresponding to differentially labeled peptides in the MS spectrum. As currently available software requires some GUI applications and is time-consuming, it is not suitable for processing large-scale proteome data. RESULTS: To resolve this difficulty, we developed an algorithm that automatically detects the peaks in each spectrum. Using this algorithm, we developed a software tool named AYUMS that automatically identifies the peaks corresponding to differentially labeled peptides, compares these peaks, calculates each of the peak ratios in mixed samples, and integrates them into one data sheet. This software has enabled us to dramatically save time for generation of the final report. CONCLUSION: AYUMS is a useful software tool for comprehensive quantitation of the proteome data generated by LC-MS/MS analysis. This software was developed using Java and runs on Linux, Windows, and Mac OS X. Please contact [email protected] if you are interested in the application. The project web page is

Usefulness and safety of 0.4% sodium hyaluronate solution as a submucosal fluid "cushion" for endoscopic resection of colorectal mucosal neoplasms: A prospective multi-center open-label trial

<p>Abstract</p> <p>Background</p> <p>Sodium hyaluronate (SH) solution has been used for submucosal injection in endoscopic resection to create a long-lasting submucosal fluid "cushion". Recently, we proved the usefulness and safety of 0.4% SH solution in endoscopic resection for gastric mucosal tumors. To evaluate the usefulness of 0.4% SH as a submucosal injection solution for colorectal endoscopic resection, we conducted an open-label clinical trial on six referral hospitals in Japan.</p> <p>Methods</p> <p>A prospective multi-center open-label study was designed. A total of 41 patients with 5–20 mm neoplastic lesions localized in the colorectal mucosa at six referral hospitals in Japan in a single year period from December 2002 to November 2003 were enrolled and underwent endoscopic resection with SH. The usefulness of 0.4% SH was assessed by the <it>en bloc </it>complete resection and the formation and maintenance of mucosal lesion-lifting during endoscopic resection. Safety was evaluated by analyzing adverse events during the study period.</p> <p>Results</p> <p>The usefulness rate was high (82.5%; 33/40). The following secondary outcome measures were noted: 1) steepness of mucosal lesion-lifting, 75.0% (30/40); 2) intraoperative complications, 10.0% (4/40); 3) time required for mucosal resection, 6.7 min; 4) volume of submucosal injection, 6.8 mL and 5) ease of mucosal resection, 87.5% (35/40). Two adverse events of bleeding potentially related to 0.4% SH were reported.</p> <p>Conclusion</p> <p>Using 0.4% SH solution enabled sufficient lifting of a colorectal intramucosal lesion during endoscopic resection, reducing the need for additional injections and the risk of perforation. Therefore, 0.4% SH may contribute to the reduction of complications and serve as a promising submucosal injection solution due to its potentially superior safety in comparison to normal saline solution.</p