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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.)

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.

Introduction: Erosive esophagitis (EE) is a severe form of gastroesophageal reflux disease commonly treated with proton pump inhibitors (PPIs). The aim of this retrospective, observational cohort study was to describe the characteristics and healthcare burden of patients with EE., Methods: We identified adults in the USA with an EE diagnosis between January  1, 2016 and February 28, 2019 in a linked dataset containing electronic health records (EHR) from the Veradigm Network EHR and claims data from Komodo Health. Patients were required to have 1 year of baseline data and 3 years of follow-up data. Patients were stratified by the number of PPI lines of therapy (LOT) during the 4-year study period. We descriptively captured patient characteristics and treatment patterns, along with all-cause and EE-related healthcare utilization and costs., Results: Among the 158,347 qualifying adults with EE, 71,958 (45.4%) had 1 PPI LOT, 14,985 (9.5%) had 2 LOTs, 15,129 (9.6%) had 3+ LOTs, and 56,275 (35.5%) did not fill a PPI prescription. Omeprazole and pantoprazole comprised more than 70% of any LOT, with patients commonly switching between the two. Mean (standard deviation) annualized all-cause and EE-related healthcare costs in the follow-up period were $16,853 ($70,507) and $523 ($3659), respectively. Both all-cause and EE-related healthcare costs increased with LOTs., Conclusions: Patients with EE are commonly treated with prescription PPIs; however, 19.0% of patients cycled through multiple PPIs. Higher PPI use was associated with a higher comorbidity burden and higher healthcare costs compared to 0 PPI use., (© 2023. The Author(s).)

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., Competing Interests: Dr. Moss has been a consultant for Takeda, has served on advisory boards for RedHill Biopharma and Phathom Pharmaceuticals regarding novel H. pylori therapies, and is a consultant for and has received research support from American Molecular Laboratories regarding molecular diagnostics for H. pylori. Dr. Chey reported being a Board member of the American College of Gastroenterology, GI on Demand, International Foundation of Functional GI Disorders, and the Rome Foundation; compensation as a consultant from AbbVie, BioAmerica, Ironwood Pharmaceuticals, QOL Medical, Nestle, Phathom Pharmaceuticals, RedHill Biopharma, Salix/Valeant, Takeda, Urovant, and Vibrant; grant/research support from BioAmerica, Commonwealth Diagnostics International, QOL Medical, Salix, and stock options in Dieta, Kiwi Bioscience, Isothrive, and Modify Health; and patents relating to methods and kits for identifying food sensitivities and intolerances, digital manometry, and a rectal expulsion device. Dr. Malfertheiner has served as a speaker for Aboca, Bayer, Biocodex, Biohit, Malesci, Menarini, Luvos, and Mayoly-Spindler, a consultant for Aboca, Bayer, Danone, and an advisory board member for Bayer, Danone, Imevax, and Phathom. Dr. Pelletier, Dr. Jacob, and Dr. Leifke are employees of Phathom Pharmaceuticals. Dr. Tremblay and Dr. Hubscher are employees of Cytel, Inc, which served as a consultant on this project. Mr. Daniele was an employee of Cytel at the time of writing., (© The Author(s), 2023.)

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., Competing Interests: ES, EEC, and HG are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Phathom Pharmaceuticals, which funded the development and conduct of this study and manuscript. KY was an employee of Analysis Group, Inc. at the time of study conduct. CP and RJ are employees of Phathom Pharmaceuticals. CWH is a consultant for Phathom Pharmaceuticals, RedHill Biopharma, Allakos, Ironwood, Neurogastrx, ISOThrive, and EndoStim. He is a speaker for RedHill Biopharma, Phathom, and Alnylman. He owns stock in Antibe Therapeutics. KS is a consultant for Fuji Film Inc., Biofermin Pharma, and Pathom Pharmaceuticals. He received lecture fees from Takeda Pharmaceutical, Mylan Inc., Japan, Zeria Pharmaceuticals, Biofermin Pharma, and Astra-Zeneca Japan., (© The Author(s), 2023.)

Approximately 36% of the United States (US) population is infected with Helicobacter pylori (HP), a known major risk factor for peptic ulcer disease and gastric cancer. HP eradication reduces the rate of complications; however, the benefits are undermined by rising rates of HP eradication treatment failure. This real-world observational cohort analysis aims to describe HP diagnostic and treatment patterns among insured patients in the US. Using diagnoses, lab results, and treatment patterns, we identified adults (18+) with new diagnoses of HP in the Veradigm Health Insights EHR Database linked to Komodo claims data (1/1/2016-12/31/2019). Patients were required to have ≥ 12 months of data pre-/post-index. We captured patient characteristics, HP-related diagnostic testing, and the use of US guideline-recommended HP eradication regimens. HP eradication rates following first-line eradication treatment were measured among patients with available lab results. Overall, 31.8% of the 60,593 included patients did not receive guideline-recommended treatment. Among the 68.2% (41,340) with first-line treatment, 80.2% received clarithromycin-based triple therapy, and 6.6% received bismuth quadruple therapy. Of the 4569 patients with a repeated course of eradication therapy, 53.4% received the same regimen as their first-line, the majority (90.7%) of whom received two rounds of clarithromycin-based triple therapy. Among the 2455 patients with results of HP non-serology testing following first-line treatment, the 180-day eradication rate was 80.2% overall, with differences based on treatments and demographics. This study highlights gaps between guideline-recommended HP management and real-world patterns, underscoring the need to improve HP testing, treatment, and follow-up practices., (© 2023. The Author(s).)

Aims: 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., Methods: 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., Results: 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., Conclusions: 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.

Introduction: 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., Areas Covered: 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., Expert Opinion: 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.

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.)

Background and Aims: Effective acid suppression is a crucial component of Helicobacter pylori ( H. pylori ) eradication regimens. Approved treatments include dual, triple, and quadruple therapies composed of certain antibiotics in combination with proton pump inhibitors (PPIs). Vonoprazan, a potassium-competitive acid blocker, provides more potent and durable acid suppression than PPIs. We compared the efficacy of vonoprazan-based therapies vs approved standard regimens using new evidence from the phase 3 pHalcon HP trial in North America and Europe., Methods: Studies reporting first-line H. pylori eradication rates from empiric treatment with Food and Drug Administration-approved therapies and vonoprazan-containing therapies were identified via bibliographic searches of systematic literature reviews and a subsequent MEDLINE/Embase search using index terms for H. pylori and eradication. Randomized controlled trials comparing 2 or more relevant comparators were included in Bayesian network meta-analyses for grouped and distinct therapies., Results: Twenty-three distinct regimens from 42 trials including 12,773 patients were identified. Vonoprazan-based triple therapy showed the highest relative efficacy (odds ratio: 2.73, 95% credible interval 2.11, 3.54) and 72.1% probability of being the best. North American, Western, and global scenarios were largely consistent. Vonoprazan-based therapies demonstrated higher odds of H. pylori eradication than each PPI-based triple therapy. Furthermore, vonoprazan-based triple therapy was superior to bismuth subcitrate quadruple therapy (odds ratio: 1.60, 95% credible interval: 1.07, 2.38)., Conclusion: Vonoprazan-based eradication regimens represent novel treatments for H. pylori infection on a global scale, offering efficacy that, in this analysis, is superior to PPI-based triple therapy and comparable or better than bismuth quadruple therapy., (© 2022 The Authors.)

Introduction: 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., Areas Covered: 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., Expert Opinion: 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.

Background and Aims: Helicobacter pylori eradication rates have declined as antibiotic resistance rates have increased. In addition, adherence to treatment guidelines is suboptimal. It is therefore important that contemporary, real-world evidence of diagnostic and treatment patterns is explored and compared with evidence-based guidelines. The Study of Acid-Related Disorders investigated unmet needs among patients with H pylori infection and past or current dyspepsia., Methods: Gastroenterologists (GIs) and family physicians (FPs) or general practitioners (GPs) treating patients with H pylori infection and past or current dyspepsia completed a physician survey and invited patients to complete a patient survey; data were also extracted from the medical records of enrolled patients., Results: Two hundred fifty-one physicians and 77 patients were enrolled. A total of 19.5% of patients were diagnosed by serology, whereas the urea breath test was used by 6.5% of GIs and 50.0% of FPs or GPs. A total of 68.6% of GIs and 79.8% of FPs or GPs selected clarithromycin, amoxicillin, and proton pump inhibitor triple therapy as their ideal first-line treatment. Physicians reported that 52.9% of patients experienced dyspepsia daily. A total of 46.8% of patients believed that complete resolution of dyspepsia would indicate effective treatment. As their treatment goal, 69.3% of physicians selected improvement in overall symptoms, whereas 92.2% of patients specified improvement in dyspepsia. Only 28.7% of physicians were satisfied with current treatment options. A total of 59.7% of patients took all of their prescribed medicine(s). A total of 59.7% of patients would prefer to take fewer pills; 45.5% would prefer convenience packs., Conclusion: This study reveals a lack of adherence to current H pylori guidelines for diagnosis, testing, and treatment. New treatment options that are more efficacious and simpler for patients to adhere to are needed., (© 2022 The Authors.)

Objectives: Levels of anticoagulation during off-pump coronary artery bypass grafting (OPCAB) remain controversial. Prolonged activated clotting time (ACT) during OPCAB increases blood loss during surgery and can also cause paradoxical increase in postoperative myocardial infarction. Shorter ACT can increase thrombotic complication. Maintaining a steady ACT level is challenging. We have used continuous heparin infusion after initial bolus during OPCAB to maintain a steady low target ACT. The objective of the present study was to assess the effectiveness and safety of heparin infusion in maintaining a steady target ACT level., Methods: This was a prospective study of consecutive OPCAB patients. ACT was measured after initial bolus dose of heparin. Once ACT of more than 200seconds was achieved, heparin infusion was started to maintain the required level of anticoagulation. CPK-MB was measured in operation room, 6 and 24hours postoperatively to rule out ischemic complication., Results: ACT could be maintained in target range with heparin infusion in 80.1% patients (161/201). Of the 40 patients with one or more ACT reading less than 200seconds, 38 patients were managed by increasing the dose of heparin infusion and only 2 patients required additional bolus dose of heparin., Conclusions: Heparin infusion maintains a steady target ACT level and avoids peaks and troughs associated with bolus doses. Lower level of anticoagulation using continuous heparin infusion does not increase ischemic complications. This is the first ever study of use of heparin infusion during OPCAB. We may conclude that heparin infusion is a safe anticoagulation strategy for OPCAB., (Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

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.

Background: The long-term benefit of bilateral internal thoracic grafts (BITA) is well established. BITA grafting is often avoided in diabetic, female, obese, elderly and other high-risk patients because of concerns for deep sternal wound infection. The objective of this study is to analyse early results of our BITA grafting and to establish the safety of BITA use in all patients., Methods: All cases of isolated consecutive unselected CABG were included in this retrospective study. BITA were used in-situ - one was used to graft left anterior descending artery and the other was used as inflow for a composite graft with radial artery. Dual inflow using in situ BITA grafting allows easy bailout by using an additional vein graft., Results: BITA was used in 574 patients out of 602 (95.35%). Incidence of early death was 1.33% (8/602), stroke 0.5% (3/602), reoperation for bleeding 0.17% (1/602). Deep sternal wound infection was not seen in any patient but nine patients (1.5%) had superficial wound infection which healed with dressing., Conclusion: We have used BITA in 95% of our unselected, consecutive off-pump CABG patients without any major wound complications. Our limited experience has shown off-pump CABG using BITA grafting can be safely adopted routinely with excellent early result., (Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)