Comparison of the Efficacy of 12-day Concomitant Quadruple Therapy versus 14-day High dose Dual Therapy as a First-line H. pylori Eradication Regimen.

Background/Aims: Helicobacter pylori (H. pylori) is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have been used for H. pylori eradication. We aimed to compare the efficacy of two different regimens as first-line H. pylori eradication regimens, in an area with high antibiotic resistance. Methods: In this RCT, we assigned 223 patients with H. pylori infection, who were naïve to treatment. They were randomly divided into two groups to receive either 12-day concomitant quadruple therapy (consisting of pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) or 14-day high dose dual therapy (consisting of esomeprazole 40 mg and amoxicillin 1 g TDS). H. pylori eradication was assessed eight weeks after the end of treatment. Results: H. pylori eradication rate by PP analysis for 12-day concomitant quadruple therapy and 14-day high dose dual therapy were 90.4% and 79.1%, respectively (p=0.02). According to ITT analysis, the eradication rates were 86.2% and 76.3%, respectively (p=0.06). Adverse drug reactions were 12.3% in high dose dual therapy and 36.8% in concomitant quadruple therapy (p<0.001). Conclusions: Twelve-day concomitant therapy seems to be an acceptable regimen for first-line H. pylori eradication in Iran, a country with a high rate of antibiotic resistance. Although, high dose dual therapy did not result in an ideal eradication rate, but it had fewer drug side effects than the 12-day concomitant regimen.

Impact of large scale, multicomponent intervention to reduce proton pump inhibitor overuse in integrated healthcare system: difference-in-difference study.

OBJECTIVE: To determine how a large scale, multicomponent, pharmacy based intervention to reduce proton pump inhibitor (PPI) overuse affected prescribing patterns, healthcare utilization, and clinical outcomes. DESIGN: Difference-in-difference study. SETTING: US Veterans Affairs Healthcare System, in which one regional network implemented the overuse intervention and all 17 others served as controls. PARTICIPANTS: All individuals receiving primary care from 2009 to 2019. INTERVENTION: Limits on PPI refills for patients without a documented indication for long term use, voiding of PPI prescriptions not recently filled, facilitated electronic prescribing of H2 receptor antagonists, and education for patients and clinicians. MAIN OUTCOME MEASURES: The primary outcome was the percentage of patients who filled a PPI prescription per 6 months. Secondary outcomes included percentage of days PPI gastroprotection was prescribed in patients at high risk for upper gastrointestinal bleeding, percentage of patients who filled either a PPI or H2 receptor antagonist prescription, hospital admission for acid peptic disease in older adults appropriate for PPI gastroprotection, primary care visits for an upper gastrointestinal diagnosis, upper endoscopies, and PPI associated clinical conditions. RESULTS: The number of patients analyzed per interval ranged from 192 607 to 250 349 in intervention sites and from 3 775 953 to 4 360 868 in control sites, with 26% of patients receiving PPIs before the intervention. The intervention was associated with an absolute reduction of 7.3% (95% confidence interval -7.6% to -7.0%) in patients who filled PPI prescriptions, an absolute reduction of 11.3% (-12.0% to -10.5%) in PPI use among patients appropriate for gastroprotection, and an absolute reduction of 5.72% (-6.08% to -5.36%) in patients who filled a PPI or H2 receptor antagonist prescription. No increases were seen in primary care visits for upper gastrointestinal diagnoses, upper endoscopies, or hospital admissions for acid peptic disease in older patients appropriate for gastroprotection. No clinically significant changes were seen in any PPI associated clinical conditions. CONCLUSIONS: The multicomponent intervention was associated with reduced PPI use overall but also in patients appropriate for gastroprotection, with minimal evidence of either clinical benefits or harms.

Vonoprazan-amoxicillin dual regimen with Saccharomyces boulardii as a rescue therapy for Helicobacter pylori: Current perspectives and implications.

Yu et al's study in the World Journal of Gastroenterology (2023) introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii (S. boulardii) for the rescue therapy against Helicobacter pylori (H. pylori), a pathogen responsible for peptic ulcers and gastric cancer. Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression, which is minimally affected by mealtime. Compared to proton pump inhibitors, which bind irreversibly to cysteine residues in the H+/K+-ATPase pump, Vonoprazan competes with the K+ ions, prevents the ions from binding to the pump and blocks acid secretion. Concerns with increasing antibiotic resistance, effects on the gut microbiota, patient compliance, and side effects have led to the advent of a dual regimen for H. pylori. Previous studies suggested that S. boulardii plays a role in stabilizing the gut barrier which improves H. pylori eradication rate. With an acceptable safety profile, the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile, thereby strengthening the applicability in clinical settings. Nonetheless, S. boulardii comes in various formulations and dosages, warranting further exploration into the optimal dosage for supplementation in rescue therapy. Additionally, larger, randomized, double-blinded controlled trials are warranted to confirm these promising results.

Association Between Vonoprazan and the Risk of Gastric Cancer After Helicobacter pylori Eradication.

BACKGROUND & AIMS: Potassium-competitive acid blockers (PCABs) have been increasingly used to treat upper gastrointestinal disorders, replacing proton pump inhibitors (PPIs). Whereas PPIs are associated with an increased risk of gastric cancer (GC) after Helicobacter pylori (Hp) eradication, it is uncertain whether PCABs carry the same risk. METHODS: Using a population-based claims database in Japan, we identified patients who were prescribed a clarithromycin-based first regimen of Hp eradication between 2015 and 2018. Patients who failed this regimen and those diagnosed with GC before or within 1 year after Hp eradication were excluded. We compared GC incidence between PCAB users and histamine type-2 receptor antagonist (H2RA) users, matching them on the basis of propensity scores calculated with considerations for age, sex, smoking, alcohol consumption, comorbidities, and co-administered medications. PCABs included only vonoprazan in this study. RESULTS: Among 54,055 patients, 568 (1.05%) developed GC during the follow-up period (mean, 3.65 years). The cumulative incidence of GC was 1.64% at 3 years, 2.02% at 4 years, and 2.36% at 5 years in PCAB users and 0.71% at 3 years, 1.04% at 4 years, and 1.22% at 5 years in H2RA users. The use of PCABs was associated with a higher GC risk (matched hazard ratio, 1.92; 95% confidence interval, 1.13-3.25; P = .016). Longer PCAB use and high-dose PCAB use were significantly associated with higher incidence of GC. Sensitivity analyses showed the risk of GC incidence among PCAB users was comparable with that of PPI users. CONCLUSIONS: The use of PCABs was associated with an increased risk of GC among Hp-eradicated patients, with duration/dose response effects.

Plants with Anti-Ulcer Activity and Mechanism: A Review of Preclinical and Clinical Studies.

Ulcer disorders including the oral mucosa, large intestine, and stomach mucosa, cause significant global health burdens. Conventional treatments such as non-steroid anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), histamine H2 receptor antagonists (H2RAs), and cytoprotective agents have drawbacks like mucosal injury, diminish gastric acid secretion, and interact with concurrent medications. Therefore, alternative therapeutic approaches are needed to tackle this health concern. Plants are rich in active metabolites in the bark, roots, leaves, fruits, and seeds, and have been utilized for medicinal purposes since ancient times. The use of herbal therapy is crucial, and regulations are necessary to ensure the quality of products, particularly in randomized studies, to assess their efficacy and safety in treating ulcer disorders. This study aims to explore the anti-ulcer activity of medicinal plants in treating peptic ulcer disease, ulcerative colitis, and aphthous ulcers. Articles were searched in Scopus and PubMed, and filtered for publication from 2013 to 2023, resulting in a total of 460 from Scopus and 239 from PubMed. The articles were further screened by title and abstract and resulted in 55 articles. Natural products, rich in active metabolites, were described to manage ulcer disease by protecting the mucosa, reducing ulcer effects, inhibiting pro-inflammatory factors, and reducing bacterial load, thus improving patients' quality of life. Natural extracts have proven effective in managing other health problems, including ulcers by reducing pain and decreasing lesions. This review provides an overview of preclinical and clinical studies on medicinal plants, focusing on their effectiveness in treating conditions like peptic ulcers, ulcerative colitis, and aphthous ulcers.

Eradication rate and adherence with high-dose amoxicillin and proton pump inhibitor as first-line treatment for Helicobacter pylori infection: Experience from University Hospital in Chile.

INTRODUCTION: In Chile, more than 70% of adults are infected by Helicobacter pylori. Clarithromycin should not be used in any regimen if there is >15% resistance to this antibiotic, being greater than 26% in our population. In this scenario, the effectiveness of triple therapy (proton pump inhibitor [PPI], clarithromycin, amoxicillin) was only 63.8%. AIM: To evaluate the eradication rate and safety of dual therapy (esomeprazole and amoxicillin) in high doses, through a prospective, observational, and descriptive study. METHODS: Patients with a positive urease test obtained in an upper digestive endoscopy were included. Any other previous H. pylori eradication regimen were excluded. All patients were treated with esomeprazole 40 mg three times a day and amoxicillin 750 mg four times a day for 14 days. The eradication rate of the dual therapy was evaluated with the H. pylori stool antigen test (the Pylori-Strip® test used) 6 weeks after completing the eradication treatment and with at least 14 days without PPI, being a negative result, confirmation of the effectiveness of this regimen. RESULTS: Of 122 patients, 106 had a negative H. pylori antigen in stool; The intention-to-treat and per protocol analysis, the eradication rates were 91.8% [95% CI: 87%-97%] and 94% [95% CI: 90%-98%], respectively. Four patients discontinued treatment due to adverse effects. Smoking and adherence to treatment were associated with eradication rate. CONCLUSIONS: In this cohort of patients with H. pylori infection, high-dose dual therapy has a high eradication rate and good adherence, raising the possibility that it could be used as first-line therapy in our country. Studies with a larger number of patients should confirm these results.

Spirulina Platensis Attenuates Rebound Dyspeptic Symptoms After Proton Pump Inhibitors' Discontinuation: Phase 2 Placebo-controlled Trial.

Context: Rebound acid hypersecretion after cessation of proton pump inhibitors (PPIs) can provoke dyspeptic symptoms. The search for alternatives to minimize the dyspeptic rebound symptoms after PPI discontinuation is warranted. Spirulina platensis, a dietary supplement made from blue-green algae, might be an alternative. Objective: The study intended to assess whether Spirulina platensis, through its anti-inflammatory and analgesic properties, can minimize rebound symptoms after PPI withdrawal. Design: The research team performed a randomized, phase 2, double-blinded, placebo-controlled clinical trial. Setting: The study took place at São Vicente de Paulo Hospital (trial registry number NCT04988347) in Passo Fundo, Brazil. Participants: Participants were 45 Brazilian patients in the clinical practice of two of the research team's member between November 2010 and February 2012, who were using PPIs regularly. Interventions: Participants underwent clinical and endoscopic evaluations after a 28-day run-in phase of 40 mg/day of pantoprazole. In the absence of a large hiatal hernia, peptic ulcer, or severe reflux esophagitis, participants stopped using PPIs, and the research team randomly assigned them to receive either 1.6g/day of spirulina or of a placebo for two months, followed by clinical and endoscopic reevaluations. Outcome measures: Using an intention-to-treat analysis, the primary outcomes postintervention were dyspepsia and typical reflux symptoms, either the appearance or maintenance of symptoms of >50% from baseline. Results: The median time of continuous PPI use was 32 months. The research team excluded two participants due to large hiatal hernias. Among the remaining 43 participants, 18 received spirulina (42%), and 25 used a placebo (58%). Two months later, 12 participants who had received spirulina (67%) and 18 who had received the placebo (72%) completed the study (P = .968). Rebound dyspepsia occurred in 10 out of 18 patients treated with spirulina (55.56%) and in 22 out of 25 patients treated with placebo (88%), with relative risk=0.63, CI95% (0.41-0.98), and P = .039. Reflux symptoms postintervention occurred in 72% and 76%, with the relative risk=0.95, CI95% (0.66-1.36), and P > .05, respectively. No significant side effects occurred in either group. The findings from endoscopy and gastric histology didn't differ between groups. Conclusions: A two-month course of Spirulina platensis was able to attenuate rebound dyspepsia but not reflux symptoms after PPI discontinuation. Considering its good safety profile, spirulina might be useful to relieve dyspeptic symptoms after PPI discontinuation.

Gastroesophageal Reflux Disease: Pathophysiology and New Treatment Trends.

Gastroesophageal reflux disease (GERD) is caused by the reflux of gastric contents into the esophagus due to a decline in esophageal clearance and anti-reflux barrier mechanisms. Mucosal injury is caused by a combination of gastric juice directly damaging the esophageal mucosa and the immune and inflammatory mechanism in which inflammatory cytokines released from the esophageal mucosal epithelium cause neutrophil migration, triggering inflammation. Gastric secretion inhibitors are the first-line treatment for GERD, but they can be combined with prokinetic agents and Chinese herbal remedies. However, pharmacotherapy cannot improve anatomical problems or prevent physical causes of GERD, such as reflux of non-acidic contents. Therefore, surgery can be warranted, depending on the pathology. Intraluminal endoscopic therapy, which is both less invasive and more effective than surgery, was recently developed and applied in Europe and the United States. In Japan, intraluminal endoscopic therapies, such as anti-reflux mucosectomy, anti-reflux mucosal ablation, and endoscopic submucosal dissection, for GERD have been independently developed.

Role of proton pump inhibitors dosage and duration in Helicobacter pylori eradication treatment: Results from the European Registry on H. pylori management.

BACKGROUND: Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication. AIM: To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg). METHODS: Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022. RESULTS: Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10 days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14 days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness. CONCLUSIONS: We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme.

An Emulated Clinical Trial of Deprescribing Proton Pump Inhibitors in Patients With Cirrhosis.

INTRODUCTION: Proton pump inhibitors (PPI) are overused and carry harms in cirrhosis. Deprescribing is advocated but has not been trialed. METHODS AND FINDINGS: We emulated a clinical trial using Medicare data. All patients were receiving chronic PPI therapy before a compensated cirrhosis diagnosis. We compared the risk death/decompensation over 3 years between continuous users and deprescribers. We find that PPI deprescription is associated with less ascites and that cumulative PPI use is associated with more ascites and encephalopathy. Ultimately, 71% of deprescribers restart PPIs. DISCUSSION: PPI deprescribing has benefits but requires ongoing support and alternative therapies for gastrointestinal symptoms.

The Efficacy and Safety of Regimens for Helicobacter pylori Eradication Treatment in China: A Systemic Review and Network Meta-Analysis.

BACKGROUND: With Helicobacter pylori's increasing antibiotic resistance, evidence of more effective treatments is lacking in China, where H. pylori prevalence is nearly 50%. Thus, we performed a network meta-analysis to compare therapeutic regimens. METHODS: Data extracted from eligible randomized controlled trials from January 2000 to September 2021 were entered into a Bayesian hierarchical random-effects model to evaluate the efficacy and safety of H. pylori eradication regimens. RESULTS: This study included 101 trials involving 21,745 patients. Vonoprazan-bismuth-containing quadruple therapy (VBQT) ranked the highest [surfaces under cumulative ranking curve (SUCRA), 83.64%], followed by high-dose amoxicillin dual therapy (HDDT) [SUCRA, 79.70%, odds ratio (OR)=1.31, 95% credible interval (CrI) (0.36, 4.72)] and proton pump inhibitor-based bismuth-containing quadruple therapy (BQT) [SUCRA, 63.59%, OR=1.59, 95% CrI (0.48, 5.24)]. HDDT [OR=2.47, 95% CrI (1.51, 4.06)], BQT [OR=2.04, 95% CrI (1.69, 2.47)], concomitant quadruple nonbismuth therapy (CT) [OR=1.93, 95% CrI (1.19, 3.15)], and sequential therapy (ST) [OR=1.86, 95% CrI (1.50, 2.32)] had higher eradication rates than standard triple therapy (TT). ST (SUCRA, 82.52%) and VBQT (SUCRA, 83.89%) had the highest eradication rate before and after 2010 in the effectiveness ranking, respectively. Furthermore, the H. pylori eradication rate of patients receiving 14-day BQT treatment was higher than that of 10-day BQT regimen [OR=2.55, 95% CI (1.84, 3.53)] and 7-day BQT regimen [OR=3.64, 95% CI (2.64, 5.01)]. CONCLUSIONS: The TT regimen was not an optimal choice in China for H. pylori eradication; VBQT, HDDT, and BQT showed better efficacy. After 2010, there is a trend toward significance that VBQT provided a higher H. pylori eradication rate in China, but with only 1 randomized controlled trial. Thus, more supportive real-world data are needed to confirm its effectiveness.

Association Between Acid-Suppressive Drugs and Risk of Rosacea: Retrospective Study Using the Korean National Health Insurance Service-National Sample Cohort.

BACKGROUND: Rosacea is a common inflammatory skin disease with multiple etiologies. Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RA) are acid suppressive drugs widely used for gastrointestinal (GI) diseases, and long-term use has been reported to be associated with dysbiosis which is a potential risk for development of rosacea. This study aimed to study the association between rosacea and acid suppressants in the Korean national cohort. METHODS: We used Korean National Health Insurance Service-National Sample Cohort data of 749,166 patients with upper GI diseases between 2001 and 2013. Duration of acid suppressants was compared between patients with and without rosacea together with other sociodemographic characteristics and hazard ratios were estimated. RESULTS: Longer use of acid suppressants was significantly associated with increased risk of rosacea. After adjustment for possible confounders, increased cumulative defined daily dose was significantly associated with risk of rosacea (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.20-2.00; P = 0.001). Other factors significantly associated with risk of rosacea include residing in the rural area (OR, 2.58; 95% CI, 2.18-3.06; P < 0.001), greater Charlson Comorbidity Index score (OR, 1.45; 95% CI, 1.15-1.83; P = 0.002), and comorbidities (malignancy, thyroid disease, and depression). CONCLUSION: Results from our study indicate that H2RA or PPI is associated with the occurrence of rosacea among patients with GI diseases in the Korean population. The risk was increased in dose-dependent manner, even after adjusting for confounding variables. Clinicians should be aware of risks associated with prolonged use of acid suppressive drugs.

Clinical efficacy of Yukgunja-tang combined with a proton pump inhibitor for refractory gastroesophageal reflux disease: study protocol for randomized, double-blind, double-dummy clinical trial.

BACKGROUND: Yukgunja-tang (YGJ) is an herbal prescription used to treat the symptoms of gastroesophageal reflux disease (GERD). Although many preclinical and clinical studies on YGJ have been conducted on GERD, there is a lack of evidence from blinded studies to exclude placebo effects. Therefore, this protocol proposes a clinical trial that is single-centered, randomized, double-blinded, double-dummy to objectively evaluate the efficacy and safety of co-administered YGJ and rabeprazole (RPZ) in patients with GERD previously treated with proton pump inhibitors (PPIs) and still experiencing symptoms. METHODS: A total of 86 participants with refractory GERD (rGERD) will be randomized in a 1:1 ratio to the treatment [YGJ and RPZ (10 mg/d)] and control groups [double-dose RPZ (20 mg/d)] for 4 weeks of treatment (weeks 0-4) followed by 4 weeks of follow-up (weeks 4-8). The Frequency Scale for the Symptoms of GERD will be analyzed for the primary endpoint. Reflux Disease Questionnaire, Reflux Symptom Score, GERD-Health Related Quality of Life, Overall Treatment Evaluation, Spleen Qi Deficiency Questionnaire, Damum Questionnaire, and dyspepsia Visual Analogue Scale will be used to evaluate treatment effects on GERD related symptoms and quality of life and to compare treatment effects by subgroups. Safety tests will be analyzed by investigating adverse events. DISCUSSION: This clinical trial will be the first rigorous double-blind, double-dummy, placebo-controlled study to precisely evaluate the efficacy and safety of the combination of YGJ and PPIs in the treatment of rGERD. The results of this study will provide a reliable clinical basis for selecting botanical drug treatments for patients with rGERD. TRIAL REGISTRATION: Clinical Research Information Service (registration number: KCT0008600, July 13, 2023, https://cris.nih.go.kr ).

Prescribing Patterns of Proton Pump Inhibitors in Germany: A Retrospective Study Including 472 146 Patients.

The aims of this study were to analyze proton pump inhibitor (PPI) users in Germany, defining and classifying them in terms of treatment appropriateness, and to analyze the PPI prescription practices of healthcare providers. The updated DGVS (Deutsche Gesellschaft für Gastroenterologie, Verdauungs-und Stoffwechselkrankheiten) gastroesophageal reflux disease (GERD) treatment guideline (published March 2023) for mild heartburn symptoms recommends carrying out a probatory treatment of mild symptoms via other medication such as antacids, alginates, and H2 blockers before escalating to PPI treatments, if the patient profile allows. This retrospective cross-sectional study was based on data from the IQVIA™ Disease Analyzer database (DA) and included adult patients (18 years or older) in 1006 general and 39 gastroenterological practices in Germany who received at least 1 PPI prescription or alginate between September 2019 and September 2021 (hereinafter referred to as the index period). Analyses included indications associated with PPI prescription, co-diagnoses, co-therapies of PPI patients, duration of PPI therapy, dosages of PPI prescriptions, and proportions of practices prescribing PPIs and alginates. A total of 472 146 patients taking PPIs and 9101 patients taking alginates were available for analysis. Very few patients (4.5%) of the total cohort were treated in complete adherence to treatment guidelines. Conditions such as gastritis and duodenitis (47.2%) and reflux diseases (38.4%) were more frequently associated with PPI prescriptions. The average PPI treatment period lasted 141 days, and 36.6% of patients were treated for >6 months. High doses were prescribed relatively often (ie, 42.8% of esomeprazole prescriptions were 40 mg, 59.1% of lansoprazole prescriptions 30 mg, 28.6% of omeprazole prescriptions 40 mg). With each practice prescribing PPIs to at least 10% of their patients; 72% of general practitioners (GPs) and 8% of GENTS (Gastroenterologists) prescribed alginates. This study highlights that discrepancies exist between clinical guidelines and real-life prescribing practices of PPIs in Germany. Particular attention should be given to the incidence of patients being prescribed high-dose or long-duration PPI with mild indications. These findings are particularly apt considering the publication (March 2023) of new guidelines on the "management of gastroesophageal reflux disease and eosinophilic esophagitis," by the DGVS.

Global research trends and hotspots of Helicobacter pylori eradication based on clinical trial registration platforms: A cross-sectional analysis.

BACKGROUND: This study aimed to obtain an overview of clinical trials on Helicobacter pylori (H. pylori) eradication and analyze the global trends and hotspots in this field. METHODS: We collected the data from clinical trials focused on H. pylori eradication in the primary clinical trial registries from 2000 to 2022 in the world. Then we analyzed the research trends and hotspots in H. pylori eradication regimens in different regions at different periods. RESULTS: A total of 780 clinical trials were included, which were mainly conducted in Asia (682), followed by Europe (59), Africa (20), North America (16), South America (7), Oceania (2). The most active countries were China (343), Iran (140), South Korea (63), and Japan (73). "Bismuth-containing quadruple therapy (BQT)" was the most studied regimen (159, 20.38 %). Additionally, clinical trials focused on potassium-competitive acid blockers (P-CABs)-based therapy, probiotics, and high-dose dual therapy (HDDT) were constantly increasing. BQT received the most attention in China (26.53 %) and Iran (22.14 %), while it was tailored therapy in South Korea (23.29 %). P-CABs-based therapy was the main reseach hotspot in Japan (61.90 %). CONCLUSION: How to eradicate H. pylori infection has been a heated research topic. BQT, P-CABs-based therapy, probiotics, and HDDT attracted the most attention in recent years.

Pilot studies of vonoprazan-containing Helicobacter pylori eradication therapy suggest Thailand may be more similar to the US than Japan.

BACKGROUND: Vonoprazan-containing Helicobacter pylori eradication is reliably effective in Japan. Its effectiveness in other countries remains unclear. Here, we examined vonoprazan-H. pylori therapies in Thailand. MATERIALS AND METHODS: This was pilot study of four different vonoprazan containing therapies. Subjects were randomized to: 14-day dual therapy (500 mg amoxicillin q.i.d. plus 20 mg vonoprazan b.i.d.), 14-day triple therapy (amoxicillin 1 g b.i.d., slow release clarithromycin-MR, 1 g daily plus vonoprazan 20 mg b.i.d.), 7-day high-dose vonoprazan triple therapy (amoxicillin 1 g b.i.d., clarithromycin-MR 1 g daily and 60 mg vonoprazan once daily), and 14-day vonoprazan triple therapy plus bismuth (amoxicillin 1 g b.i.d., clarithromycin-MR 1 g daily, vonoprazan 20 mg b.i.d., and bismuth subsalicylate 1048 mg b.i.d.). Eradication was confirmed 4 weeks after therapy. Antimicrobial susceptibility and CYP3A4/5 genotyping were performed. RESULTS: One hundred H. pylori-infected patients (mean age 54.3 ± 13 years, 51% men) were randomized. All were CYP3A4 extensive metabolizers. Cure rates with both 14-day vonoprazan dual therapy and 14-day triple therapy were low: 66.7%; 95% CI = 43-85% (14/21), and 59.3%; 95% CI = 39-78%) (16/27), respectively. In contrast, 7-day high-dose vonoprazan triple therapy and 14-day vonoprazan triple plus bismuth proved effective 92.3%; 95% CI = 75%-99% (24/26) and 96.2%; 95% CI = 80%-100% (25/26), respectively. CONCLUSION: Both 14-day vonoprazan dual and triple therapy were ineffective for H. pylori eradication in Thailand. Higher dosage of vonoprazan, and/or the addition of bismuth may be required to achieve high H. pylori eradication rates. High-dose vonoprazan triple therapy and vonoprazan triple therapy adding bismuth might be used as first-line treatments in some regions with high efficacy irrespective of CYP3A4/5 genotype and clarithromycin resistance.

Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial.

OBJECTIVE: To compare the efficacy of curcumin versus omeprazole in improving patient reported outcomes in people with dyspepsia. DESIGN: Randomised, double blind controlled trial, with central randomisation. SETTING: Thai traditional medicine hospital, district hospital, and university hospitals in Thailand. PARTICIPANTS: Participants with a diagnosis of functional dyspepsia. INTERVENTIONS: The interventions were curcumin alone (C), omeprazole alone (O), or curcumin plus omeprazole (C+O). Patients in the combination group received two capsules of 250 mg curcumin, four times daily, and one capsule of 20 mg omeprazole once daily for 28 days. MAIN OUTCOME MEASURES: Functional dyspepsia symptoms on days 28 and 56 were assessed using the Severity of Dyspepsia Assessment (SODA) score. Secondary outcomes were the occurrence of adverse events and serious adverse events. RESULTS: 206 patients were enrolled in the study and randomly assigned to one of the three groups; 151 patients completed the study. Demographic data (age 49.7±11.9 years; women 73.4%), clinical characteristics and baseline dyspepsia scores were comparable between the three groups. Significant improvements were observed in SODA scores on day 28 in the pain (-4.83, -5.46 and -6.22), non-pain (-2.22, -2.32 and -2.31) and satisfaction (0.39, 0.79 and 0.60) categories for the C+O, C, and O groups, respectively. These improvements were enhanced on day 56 in the pain (-7.19, -8.07 and -8.85), non-pain (-4.09, -4.12 and -3.71) and satisfaction (0.78, 1.07, and 0.81) categories in the C+O, C, and O groups, respectively. No significant differences were observed among the three groups and no serious adverse events occurred. CONCLUSION: Curcumin and omeprazole had comparable efficacy for functional dyspepsia with no obvious synergistic effect. TRIAL REGISTRATION NUMBER: TCTR20221208003.

The association between proton pump inhibitors and hyperparathyroidism: a potential mechanism for increased fracture-results of a large observational cohort study.

Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture; however, the mechanism is unclear. PPI users taking calcium supplements were more likely to have hyperparathyroidism compared to non-users (OR 1.56, CI 1.08-2.23, p = 0.018). This highlights the importance of monitoring PPI use, especially in older adults. PURPOSE: Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture. Hyperparathyroidism may be implicated, but few studies have considered this relationship. This study evaluated the relationship between PPI use and hyperparathyroidism in older adults. METHODS: Participants were from the TUDA study, a large cross-sectional cohort of older Irish adults. Participants with an estimated glomerular filtration rate (eGFR) < 30 ml/min and serum calcium > 2.5 mmol/l were excluded to avoid hyperparathyroidism due to chronic renal disease and primary hyperparathyroidism. Hyperparathyroidism was defined as a parathyroid hormone (PTH) > 65 pg/ml. Multivariate regression models were used to analyse the relationship between PPI use and hyperparathyroidism. RESULTS: A total of 4139 participants met the inclusion criteria, of whom 37.8% (n = 1563) were taking PPI medication. PPI use was identified in 41.4% of calcium supplement users and 35.4% of non-calcium supplement users. Overall, compared to non-users of PPIs, those taking PPIs were older (74.8 vs 72.9 years, p < 0.001) and had a higher prevalence of hyperparathyroidism (17.8 vs 11.0%, p < 0.001). In those taking calcium supplements (but not in non-users), PPI use was significantly associated with hyperparathyroidism (OR 1.56, CI 1.08-2.23, p = 0.018) after adjusting for age, sex, body mass index, serum vitamin D, eGFR, timed-up-and-go, dairy intake, medications, and comorbidities. DISCUSSION: The results are consistent with the hypothesis of PPIs reducing calcium absorption, leading to a rise in PTH which could mediate increased fracture risk. No relationship of PPI use with hyperparathyroidism was observed in non-users of calcium supplements, possibly owing to lower dietary calcium intake. These results highlight the importance of monitoring PPI use, especially in older adults at risk of fracture.

Efficacy and safety of vonoprazan-based dual therapy and esomeprazole-based dual therapy in eradicating primary Helicobacter pylori infection: A propensity score matching analysis.

BACKGROUND: According to the Maastricht VI/Florence consensus report, potassium-competitive acid blockers (P-CAB) may improve Helicobacter pylori eradication treatment. MATERIALS AND METHODS: A total of 213 H. pylori treatment-naive patients aged between 18 and 70 years were treated with two regimens. The two regimens are VDT: 20 mg vonoprazan twice a day and 1 g amoxicillin three times daily and EDT: 20 mg esomeprazole four times a day and 750 mg amoxicillin four times daily. 13 C-urea breath tests were used to evaluate eradication rate 4-6 weeks after treatment. Based on propensity score matching (PSM), this retrospective study analyzed the eradication rates, adverse events (AEs), compliance, and antibiotic resistance rates in VDT and EDT groups. RESULTS: On intention-to-treat (ITT) analysis, the eradication rate in VDT group (89.0%; 95% CI 81.7-96.3) was non-inferior to that in EDT group (87.7%; 95% CI 80.1-95.3; p = 0.796). The corresponding per-protocol (PP) eradication rates were 94.1% (95% CI 88.4-99.8) and 92.8% (95% CI 86.7-98.9; p = 1.000), respectively. There were no significant between-group differences with respect to compliance or incidence of AEs. CONCLUSIONS: The efficacy and safety of 14-day VDT and EDT were comparable. Therefore, 14-day VDT or EDT may be recommended for the first-line treatment of H. pylori infection.