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Gastroesophageal reflux disease (GERD) and Helicobacter pylori (H. pylori) infection are different disease states that are united by the core role of acid suppression in their management. In GERD, proton pump inhibitors (PPIs) have long been standard therapy based on abundant positive clinical trial data supporting their efficacy and safety. In H. pylori, PPIs are also a critical element of therapy in combination with 1 or more antibiotics to achieve and maintain a pH that maximizes the efficacy of therapy. Despite the considerable clinical success and widespread use of PPIs, room remains for agents with differentiated pharmacokinetic and pharmacodynamic profiles. The potassium-competitive acid blockers (PCABs) are mechanistically distinct from PPIs but are acid-stable and do not require activation of the proton pump by coadministration of food. In pharmacodynamic studies, these agents have shown greater durations of acid suppression above the critical threshold of pH 4 (for GERD) and pH 6 (for H. pylori), which have been shown to optimize therapeutic efficacy in these settings. These results have translated in clinical studies to similar and, in some cases, improved outcomes relative to PPIs in these disease states. This review summarizes current knowledge on the physiology of acid secretion, pathophysiology and management of GERD and H. pylori, and key characteristics and clinical trial data for PPIs and PCABs. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori eradication rates achieved with clarithromycin-based triple therapies are declining due to antibiotic resistance, but data regarding temporal changes in efficacy with these eradication therapies are scarce. Objective: To evaluate the efficacy of clarithromycin-based triple eradication regimens over time. Design: A comprehensive literature review and time-trend analysis. Data sources and methods: Bibliographies of recently published systematic literature reviews were searched and supplemented with a targeted literature review conducted using Medline and Embase databases and ProQuest from conception to May 2021. Studies reporting H. pylori eradication rates of clarithromycin-based triple therapies were included and temporal trends were estimated using a random-effects model. Results: Eradication rates for triple therapies containing proton pump inhibitors (PPIs), clarithromycin, and amoxicillin showed a significant decline over the past 23 years (p = 0.0315). However, this decline was not significant when eradication rates achieved with vonoprazan-based triple therapy were included (p = 0.3910). Conclusion: Vonoprazan-based triple therapy partially mitigated the decline in eradication rates seen with PPI-based triple therapy, likely due to more powerful acid suppression of vonoprazan. [ABSTRACT FROM AUTHOR]

Background: Japanese guidelines recommend triple therapy with vonoprazan or a proton pump inhibitor (PPI) in combination with antibiotics to treat Helicobacter pylori (H. pylori) infection. While studies have shown improved eradication rates and reduced costs with vonoprazan versus PPIs, there is little data describing healthcare resource use (HCRU) and treatment patterns. Objectives: To compare patients treated with a vonoprazan-based or PPI-based regimen for H. pylori infection in Japan in terms of their characteristics, HCRU, healthcare costs, clinical outcomes, and treatment patterns. Design: Retrospective matched cohort. Methods: We used data from the Japan Medical Data Center claims database (July 2014–January 2020) to identify adult patients with H. pylori infection and a first observed use of vonoprazan or a PPI in 2015 or later (index date). Patients prescribed a vonoprazan-based or a PPI-based regimen were matched 1:1 using propensity score matching. HCRU, healthcare costs, diagnostic tests, a proxy for H. pylori eradication (i.e. no triple therapy with amoxicillin in combination with metronidazole or clarithromycin >30 days after the index date), and second-line treatment were described during the 12-month follow-up period. Results: Among 25,389 matched pairs, vonoprazan-treated patients had fewer all-cause and H. pylori- related inpatient stays and outpatient visits than PPI-treated patients, resulting in lower all-cause healthcare costs [185,378 Japanese yen (JPY) versus 230,876 JPY, p < 0.001]. Over 80% of patients received a post-treatment test for H. pylori. Fewer vonoprazan-treated than PPI-treated patients subsequently received an additional triple regimen for H. pylori infection (7.1% versus 20.0%, p < 0.001) or a prescription for vonoprazan or a PPI as monotherapy (12.4% versus 26.4%, p < 0.001) between 31 days and 12 months after the index date. Conclusion: Patients with H. pylori infection who were treated with vonoprazan-based therapy had lower rates of subsequent H. pylori treatment, lower overall and H. pylori -related HCRU, and lower healthcare costs than patients treated with PPI-based therapy. [ABSTRACT FROM AUTHOR]

The study objectives were to 1) characterize the cost drivers of patients with Helicobacter pylori (HP) and 2) estimate HP-related cost savings following lab-confirmed HP eradication with US guideline-recommended treatment compared to failed eradication. We identified adults newly diagnosed with HP between 1/1/2016–12/31/2019 in the Veradigm Electronic Health Record Database linked to claims data (earliest HP diagnosis = index date). For the overall costs analysis, we required patients to have data available for ≥12 months before and after the index date. Then, we used multivariable modeling to assess the marginal effects of comorbidities on all cause-healthcare costs in the 12 months following HP diagnosis. For the eradication savings analysis, we identified patients with ≥1 HP eradication regimen, a subsequent HP lab test result, and ≥1 year of data after the test result. Then we used multivariable modeling to estimate HP-related cost while adjusting for eradication status, demographics, post-testing HP-related clinical variables, and the interactions between eradication status and each HP-related clinical variable. The overall cost analysis included 60,593 patients with HP (mean age 54.2 years, 65.5% female). Mean (SD) 12-month unadjusted all-cause costs were $23,693 ($78,089). Rare comorbidities demonstrated the highest marginal effect. The marginal effects of gastric cancer and PUD were $15,705 and $7,323, respectively. In the eradication savings analysis, 1,835 (80.0%) of the 2295 patients had lab test-confirmed HP eradication. Compared to failed eradication, there were significant one-year cost savings among patients with successful HP eradication and select conditions: $1,770 for PUD, $518 for atrophic gastritis, $494 for functional dyspepsia, and $352 for gastritis. The healthcare costs of patients with HP are partially confounded by their burden of high-cost comorbidities. In the subset of patients with available results, confirmed vs. failed eradication of HP was associated with short-term cost offsets among those with specific to HP-related sequelae. Helicobacter pylori (HP) is a common infection. We aimed to better understand healthcare costs for people infected with HP. Specifically, we were interested in 1) investigating whether complications from HP were causing high costs. 2) whether successful eradication of HP would lead to lower healthcare costs. We captured data on adults diagnosed with HP between 2016 and 2019. The data used in this study came from medical records and insurance bills. In the first part of the study, we found that patients with HP often have other health issues, and these other health issues were driving high healthcare costs. The majority of cost savings associated with HP eradication accrue from the prevention of potential complications of long-term infection, such as peptic ulcer disease and, rarely, gastric cancer. [ABSTRACT FROM AUTHOR]

Erosive esophagitis (EE) occurs when refluxate from the stomach causes T-lymphocyte infiltration of the esophageal mucosa, resulting in mucosal breaks. Currently, therapy with proton-pump inhibitors (PPIs) is the standard treatment for EE in the United States, but few comprehensive reviews exist on the efficacy of PPIs in US populations. Here, we present the most contemporary, thorough analysis of PPI efficacy rates, and identify and characterize patient subgroups at risk for poor healing outcomes. We searched the literature to identify studies reporting rates of endoscopic healing and maintained healing of EE with PPI therapies in the US and found a paucity of recent evidence and real-world evidence. Twenty-two studies from 2009 and earlier were included in the final dataset. Rates of EE healing with PPIs were highest after 8 weeks of treatment, with over 80% of patients in most treatment arms demonstrating endoscopic healing, compared to lower efficacy (<80%) at 4 weeks. Rates of maintained healing with PPIs at 6 and 12 months were mostly lower than 80%, although the data were limited. Symptomatic patients and those with severe EE were less likely to achieve healing. Obese patients experienced similar healing rates as non-obese patients. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (Hp) is causal in benign and malignant gastrointestinal diseases. Accordingly, current guidelines recommend Hp eradication in patients with active infection. Unfortunately, treatment failure is common, exposing patients to complications associated with persistent Hp infection and consequences of repeated treatment, including promotion of antibiotic resistance. In the United States (US), data regarding eradication rates with available therapies are limited. Moreover, the clinical and economic burden of eradication treatment failure have not been thoroughly described. We aimed to characterize Hp eradication rates and the clinical consequences and associated costs of persistent Hp infection among US adults. We conducted focused literature reviews using initial searches in Embase, MEDLINE, and Cochrane Database of Systematic Reviews via Ovid followed by manual searches to identify relevant publications. Hp eradication rates were suboptimal, with most studies reporting rates ≤80% with clarithromycin-based triple therapy and bismuth quadruple therapy. There was direct evidence supporting numerous benefits of successful Hp eradication, including decreased risk of recurrent or complicated peptic disease and non-cardia gastric cancer. Cost benefits of eradication were related to mitigation of conditions associated with persistent Hp infection, (e.g. complicated peptic ulcer disease, and gastric cancer) which altogether exceed US$5.3 billion. [ABSTRACT FROM AUTHOR]

Electrocatalytic nitric oxide reduction reaction (NORR) is a promising method for generating NH 3 and eliminating harmful NO pollutants. However, developing a NORR catalyst for NH 3 synthesis with low cost and high efficiency is still challenging. We here report a series of single-atom catalysts (SACs), designed by embedding nine different transition metals from Sc to Cu in S-vacant WS 2 monolayer (TM@WS 2 ), and investigate the electrocatalytic performance for NORR process using the dispersion-corrected density functional theory (DFT) calculations. Among the nine SACs, Cu-based one shows a strong binding to the WS 2 surface and high selectivity for the NORR process, and also it greatly inhibits the competing hydrogen evolution reaction (HER). Through ab initio molecular dynamics (AIMD) simulations, the thermal stability of SAC is assessed and found no structure deformation even at 500 K temperature. With the advent of energy descriptor, all possible reactive pathways including distal and alternating mode at both N- and O-end configurations for NH 3 production were explored. We predicted that the Cu@WS 2 SAC exhibits remarkable catalytic activity and selectivity with lowest limiting potential of-0.41 V via the N-alternating pathway. Our study emphasize that the transition metal dichalcogenide (TMDC) based SACs are potential candidates for converting NO to NH 3 , and this opens a new avenue in designing NORR catalysts with high catalytic performance., (© 2024 Wiley-VCH GmbH.)

Objective: Management of erosive oesophagitis (EE) remains suboptimal, with many patients experiencing incomplete healing, ongoing symptoms, and relapse despite proton pump inhibitor (PPI) treatment. The Study of Acid-Related Disorders investigated patient burden of individuals with EE in a real-world setting., Design: US gastroenterologists (GIs) or family physicians (FPs)/general practitioners (GPs) treating patients with EE completed a physician survey and enrolled up to four patients with EE for a patient survey, with prespecified data extracted from medical records., Results: 102 GIs and 149 FPs/GPs completed the survey; data were available for 73 patients (mean age at diagnosis, 45.4 years). Omeprazole was healthcare professional (HCP)-preferred first-line treatment (60.8% GIs; 56.4% FPs/GPs), and pantoprazole preferred second line (29.4% and 32.9%, respectively). Price and insurance coverage (both 55.5% HCPs) and familiarity (47.9%) key drivers for omeprazole; insurance coverage (52.0%), price (50.0%), familiarity (48.0%), initial symptom relief (46.0%), and safety (44.0%) key drivers for pantoprazole. Only 49.3% patients took medication as instructed all the time; 56.8% independently increased medication frequency some of the time. Despite treatment, 57.5% patients experienced heartburn and 30.1% regurgitation; heartburn was the most bothersome symptom. 58.9% patients believed that their symptoms could be better controlled; only 28.3% HCPs were very satisfied with current treatment options. 83.6% patients wanted long-lasting treatment options. Fast symptom relief for patients was a top priority for 66.1% HCPs, while 56.6% would welcome alternatives to PPIs., Conclusion: This real-world multicentre study highlights the need for new, rapidly acting treatments in EE that reduce symptom burden, offer durable healing and provide symptom control., Competing Interests: Competing interests: CP and RJ are employees of Phathom Pharmaceuticals. All other authors are consultants to Phathom Pharmaceuticals., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Off-pump coronary artery bypass grafting in patients with left ventricular dysfunction has proven to be advantageous. However, it carries risk of emergency conversion to cardiopulmonary bypass. We have successfully used an intra-aortic balloon pump to prevent such conversion. The objective of the present study was to evaluate if intravenous nicorandil infusion reduces the incidence of intraoperative intra-aortic balloon pump insertion., Methods: Consecutive cases of isolated off-pump coronary artery bypass surgery performed by a single surgeon were studied. Patients were divided into two groups. The first group did not receive nicorandil, and the second group received intraoperative nicorandil infusion (started in the operating room after central line insertion)., Results: A total of 375 patients were included in the study. Four patients in the non-nicorandil group and the patients in nicorandil group were on preoperative intra-aortic balloon pump and hence excluded from the study. After routine use of nicorandil infusion, incidence of intra-aortic balloon pump insertion during off-pump coronary artery bypass surgery decreased from 12.4% (21/169) to 2.9% (6/206)., Conclusions: Nicorandil infusion significantly (P = 0.007) reduced the incidence of intra-aortic balloon pump insertion in our series. In patients with left ventricular dysfunction (ejection fraction ≤ 30%), this difference (P = 0.008) assumes a special significance as off-pump bypass surgery is considered high risk in this subset. Nicorandil is an inexpensive drug, and the reduction in cost of surgery by avoiding intra-aortic balloon pump insertion is an added advantage. The use of nicorandil infusion during off-pump coronary artery bypass may result in favorable patient outcomes by reducing invasive intra-aortic balloon pump insertion during off-pump coronary artery bypass grafting.