Inhibition Of Gastric Acid Secretion Research Articles

Inhibition of gastric acid secretion with omeprazole affects fish specific dynamic action and growth rate: Implications for the development of phenotypic stomach loss.

An acid-secreting stomach provides many selective advantages to fish and other vertebrates; however, phenotypic stomach loss has occurred independently multiple times and is linked to loss of expression of both the gastric proton pump and the protease pepsin. Reasons underpinning stomach loss remain uncertain. Understanding the importance of gastric acid-secretion to the metabolic costs of digestion and growth will provide information about the metabolic expense of acid-production and performance. In this study, omeprazole, a well characterized gastric proton pump inhibitor, was used to simulate the agastric phenotype by significantly inhibiting gastric acidification in Nile tilapia. The effects on post-prandial metabolic rate and growth were assessed using intermittent flow respirometry and growth trials, respectively. Omeprazole reduced the duration (34.4%) and magnitude (34.5%) of the specific dynamic action and specific growth rate (21.3%) suggesting a decrease in digestion and assimilation of the meal. Gastric pH was measured in control and omeprazole treated fish to confirm that gastric acid secretion was inhibited for up to 12 h post-treatment (p < 0.05). Gastric evacuation measurements confirm a more rapid emptying of the stomach in omeprazole treated fish. These findings reinforce the importance of stomach acidification in digestion and growth and present a novel way of determining costs of gastric digestion.

Efficacy and safety of high-dose esomeprazole-amoxicillin dual therapy for Helicobacter pylori rescue treatment: a multicenter, prospective, randomized, controlled trial.

Background:High-dose dual therapy (HDDT) with proton pump inhibitors (PPIs) and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of high-dose PPI–amoxicillin dual therapy and bismuth-containing quadruple therapy for H. pylori rescue treatment.Methods:This was a prospective, randomized, multicenter, non-inferiority trial. Patients recruited from eight centers who had failed previous treatment were randomly (1:1) allocated to two eradication groups: HDDT (esomeprazole 40 mg and amoxicillin 1000 mg three times daily; the HDDT group) and bismuth-containing quadruple therapy (esomeprazole 40 mg, bismuth potassium citrate 220 mg, and furazolidone 100 mg twice daily, combined with tetracycline 500 mg three times daily; the tetracycline, furazolidone, esomeprazole, and bismuth [TFEB] group) for 14 days. The primary endpoint was the H. pylori eradication rate. The secondary endpoints were adverse effects, symptom improvement rates, and patient compliance.Results:A total of 658 patients who met the criteria were enrolled in this study. The HDDT group achieved eradication rates of 75.4% (248/329), 81.0% (248/306), and 81.3% (248/305) asdetermined by the intention-to-treat (ITT), modified intention-to-treat (MITT), and per-protocol (PP) analyses, respectively. The eradication rates were similar to those in the TFEB group: 78.1% (257/329), 84.2% (257/305), and 85.1% (257/302). The lower 95% confidence interval boundary (−9.19% in the ITT analysis, − 9.21% in the MITT analysis, and −9.73% in the PP analysis) was greater than the predefined non-inferiority margin of −10%, establishing a non-inferiority of the HDDT group vs. the TFEB group. The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group (11.1% vs. 26.8%, P < 0.001). Symptom improvement rates and patients’ compliance were similar between the two groups.Conclusions:Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy, with fewer adverse effects and good treatment compliance, suggesting HDDT as an alternative for H. pylori rescue treatment in the local region.Trial registration:Clinicaltrials.gov, NCT04678492.

Iron absorption and phosphate-lowering effects of ferric citrate hydrate are not influenced by gastric acid secretion inhibitors in patients with chronic kidney disease: a retrospective post hoc analysis

BackgroundFerric citrate hydrate (FC), an oral iron product is approved as iron preparation for iron deficiency anemia and phosphate binder for chronic kidney disease (CKD). We investigated whether gastric acid secretion inhibitors (GASI) influenced on iron absorption and phosphate-lowering effects of FC.MethodsTwo phase 3 studies of FC for treatment of hyperphosphatemia in CKD patients (non-dialysis-dependent, 12 weeks, and hemodialysis, 52 weeks), were retrospectively analyzed. Patients were divided into with or without concomitant GASI and levels of iron- and phosphate-related parameters were analyzed.ResultsIn non-dialysis study (FC, 60 patients; placebo, 30 patients), 14 FC patients and 14 placebo patients used GASI. No significant differences were found between the FC and placebo groups for adjusted mean differences (95% CI) of changes from baseline to end of treatment (EOT) in serum ferritin [104.84 ng/mL (35.97, 173.71) with GASI vs 145.30 ng/mL (96.34, 194.25) without GASI, P = 0.34], and transferrin saturation (TSAT) [12.56% (− 0.83, 25.95) with GASI vs 18.56% (8.15, 28.98) without GASI, P = 0.49]. In hemodialysis study, 95/180 patients used GASI. Mean changes (SD) from baseline to EOT in serum ferritin were 166.32 ng/mL (153.70) with GASI and 155.16 ng/mL (139.47) without GASI, and for TSAT were 16.60% (19.44) with GASI and 16.02% (18.81) without GASI. In both studies, there were no differences in the changes from baseline to EOT in serum phosphate between with and without GASI cohorts.ConclusionGASI did not influence on the changes in serum ferritin, TSAT and serum phosphate by FC administration.

Vonoprazan-associated nephrotoxicity: extensive real-world evidence from spontaneous adverse drug reaction reports

Vonoprazan-associated nephrotoxicity: extensive real-world evidence from spontaneous adverse drug reaction reports

Mucoprotectants

The gastric mucosa is constantly exposed to gastric acid and pepsin. Moreover, various factors, such as nonsteroidal anti-inflammatory drugs, &lt;i&gt;Helicobacter pylori&lt;/i&gt; infection, ethanol, stress, and aging, can damage the gastrointestinal mucosa. Nevertheless, even under these harsh conditions, the gastric mucosa is structurally maintained by various processes, referred to as “defense mechanisms.” Mucosal defense mechanisms are complicated; however, the most important elements are known to be the gastric epithelium and mucus layer, which are stimulated by prostaglandins and nitric oxide. Peptic ulcers result from an imbalance between these aggressive and defensive factors. Methods to prevent or treat peptic ulcers can be classified into two classes: 1) inhibition of gastric acid secretion and 2) promotion of mucosal defense factors. Drugs that reduce gastric acid secretion include proton pump inhibitors, histamine H2 antagonists, and potassium-competitive acid blockers. Mucoprotectants prevent peptic ulcers by promoting peptic ulcer healing. Mucoprotectants can work by two main mechanisms of action; one is independent of prostaglandins, and the other is related to prostaglandin activity. Bismuth, sucralfate, and misoprostol have been traditionally used to protect the gastric mucosa from gastric acid and pepsin. Currently, several mucoprotectants, such as rebamipide, ecabet sodium, polaprezinc, teprenone, and DA-9601, are prescribed in clinical practice. This review aims to provide information to clinicians by examining the characteristics of each drug, including their mechanism of action, research results, effective dose, and side effects.

Effects of Gastric Acid Secretion Inhibitors for Ventilator-Associated Pneumonia.

Objective: This study analyzed the association of gastric acid secretion inhibitors (GASIs) [including proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs)] with the occurrence of ventilator-associated pneumonia (VAP) and in-hospital mortality in patients who received invasive mechanical ventilation (IMV). Method: Patients who received IMV and used GASI were included based on records in the MIMIC-IV database. The relationships of GASIs with VAP and the in-hospital mortality were determined using univariate and multivariate logistic regression analyses. Also, the effects of GASIs in some subgroups of the population were further analyzed. Results: A total of 18,669 patients were enrolled, including 9191 patients on H2RAs only, 6921 patients on PPIs only, and 2557 were on a combination of the two drugs. Applying logistic regression to the univariate and multivariate models revealed that compared with H2RAs, PPIs had no significant effect on the incidence of VAP, and the combination of H2RAs and PPIs was a risk factor for VAP. Compared with H2RAs, univariate logistic regression revealed that, PPIs and combine the two drugs were both risk factors for in-hospital mortality, but multivariate logistic regression showed that they were not significantly associated with in-hospital mortality. In subgroup analysis, there were interaction in different subgroups of age, PCO2, myocardial infarct, congestive heart failure (P for interaction<0.05). Conclusion: Compared with H2RAs, PPIs did not have a significant association with either VAP or in-hospital mortality; the combination of H2RAs and PPIs was risk factor for VAP, but did not have a significantly associated with in-hospital mortality.

MO525: Iron absorption and phosphate-lowering effects of ferric citrate hydrate are not influenced by gastric secretion inhibitors in patients with chronic kidney disease

Abstract BACKGROUND AND AIMS Ferric citrate hydrate (FC, Riona®), an oral iron-based phosphate binder in chronic kidney disease (CKD) patients, is also approved as an iron preparation for iron-deficiency anemia (IDA) in Japan. In the USA, ferric citrate (Auryxia®) is approved as a phosphate binder for dialysis-dependent CKD and an iron replacement product for the treatment of IDA in patients with CKD not on dialysis. Ingested iron is dissolved at a low pH of the secreted gastric acid in the stomach, which is an important process for its effective absorption [1]. Patients taking gastric acid secretion inhibitors (GASI), such as proton pump inhibitors and histamine-2 receptor antagonists, showed decreased iron absorption and increased risk of iron deficiency, which were dose- and treatment-duration-dependent [2]. The increase in the intragastric pH by concomitantly use of GASI might be affected on FC's iron absorption effect. METHOD We have conducted a retrospective study using data from two previous clinical studies to investigate FC in CKD patients with hyperphosphatemia. A 12-week, phase 3, multicenter, randomized, double-blind, placebo-controlled study in non–dialysis-dependent (ND) CKD patients (FC, n = 60, ; placebo, n = 30) (CTI-111 435) [3], and a 52-week, phase 3, multicenter, open-label, dose-titration study in CKD patients undergoing hemodialysis (HD) (FC, n = 180) (CTI-111 437) [4] were divided into with or without GASI, and levels of iron and phosphate related parameters were analyzed. RESULTS In ND patients, approximately 25% in FC (n = 14) and 50% (n = 14) in placebo used GASI. Mean [standard deviation (SD)] changes from baseline to end of treatment (EOT) in serum ferritin (ng/mL) were 109.83 (104.46) in FC with GASI, 142.68 (94.28) in FC without GASI, −22.49 (74.85) in placebo with GASI, and −3.43 (43.58) in placebo without GASI (Fig. 1a). Those in transferrin saturation (TSAT, %) were 16.64 (30.13) in FC with GASI, 17.07 (17.56) in FC without GASI, 2.86 (14.68) in placebo with GASI, and 1.31 (9.75) in placebo without GASI (Figure 1b). The mean (SD) dose of FC with or without GASI were 3240 mg/day (approximately 778 mg ferric iron) with GASI (n = 14) and 3445 mg/day (approximately 827 mg ferric iron) without GASI (n = 46), respectively. In HD patients, approximately 50% (n = 95) used GASI. Mean changes (SD) from baseline to EOT in serum ferritin (ng/mL) were 166.32 (153.70) with GASI and 155.16 (139.47) without GASI, and in TSAT (%) were 16.60 (19.44) with GASI and 16.02 (18.81) without GASI, respectively. The mean (SD) dose of FC with or without GASI were 2619 mg/day (approximately 629 mg of ferric iron) with GASI (n = 95) and 2854 mg/day (approximately 685 mg or ferric iron) without GASI (n = 85), respectively. In both studies, there were no differences in the changes from baseline to EOT in serum phosphate between with or without GASI. CONCLUSION GASI did not interfere with iron absorption and phosphate-lowering effects of FC in CKD patients with hyperphosphatemia.

Tablets in Capsule as Strategy to Improve Adherence in Patients Cardiovascular Disease

Aims: The main objective of this work has been the development of delayed-release hard capsule containing mini-tablets of two-platelet antiaggregant, acetylsalicylic acid and clopidogrel, for the treatment of patients suffering from acute coronary syndrome at risk of gastrointestinal bleeding, therefore jointly is administered an inhibitor of gastric acid secretion, the ranitidine.&#x0D; Study Design: Design of mini-tablets into a capsule for the treatment of acute coronary syndrome.&#x0D; Methodology: For the galenic preparation of the three mini-tablets, an in-depth study of the choice of excipients and the most appropriate manufacturing methodology was carried out. Once the suitability of the mixture for use in direct compression was determined, which is the selected technological method, as it is the most profitable and involves less time, the mini-tablets were prepared and their physical characterization. Tablet appearance and physical characteristics such as dimensions, thickness, mass, resistance to crushing, friability, disintegration time and content uniformity met the requirements established according to pharmacopoeia to ensure the quality of the tablets.&#x0D; Results: The final formulation consists of the grouping of mini-tablets of three drugs in a delayed-release hard capsule ("tablets-in-capsule") for the treatment of patients suffering from acute coronary syndrome at risk of gastrointestinal bleeding. All tablets show resistance to crushing, disintegration, and friability features that strictly meet pharmacopoeia requirements.&#x0D; Conclusion: Adherence to treatment is increased because the concomitant administration of three active ingredients is unified in a single pharmaceutical dosage form.

A narrative review of postoperative bleeding in patients with gastric cancer treated with endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD) is now considered a standard treatment for selected patients with early gastric cancer. Compared with endoscopic mucosal resection (EMR), ESD provides a higher complete resection rate (R0), and therefore, a lower local recurrence rate. However, ESD is a more time-consuming procedure, creating a wider and deeper ulcer floor which may cause complications. Post-ESD bleeding is one of them. Although most post-ESD bleedings can be controlled by endoscopic hemostasis at the time of operation, some bleeding after ESD may result in serious conditions such as hemorrhagic shock. Even with preventive methods such as ulcer closure, the application of fibrin glue and polyglycolic acid shielding, acid secretion inhibitors and hemostasis on second-look endoscopy, our experiences told us that post-ESD bleeding cannot be entirely avoidable, especially for patients with big size ulcer bed, anticoagulants/antithrombosis and chronic kidney diseases. The present review first defined post-ESD bleeding, then the incidence, the risk factors, such as the location of operative lesion, the size and depth, chronic kidney diseases, the impacts of anticoagulant and antithrombotic agents. We finally reviewed the managements of post-ESD bleeding, including approaches of coagulating potential bleeding spots during the procedure, lesion closure, lesion shielding and the application of gastric acid secretion inhibitors.

Evidence-based treatments for eosinophilic esophagitis: insights for the clinician.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. Left untreated, EoE progresses to fibrous remodeling and stricture formation that impairs quality of life. Therefore, EoE requires either repeated treatments or maintenance therapy. Current guidelines recommend swallowed topical corticosteroids (STCs), proton-pump inhibitors (PPIs), or dietary intervention as initial options to induce and maintain long-term disease remission. Impractical exclusive elemental diets and suboptimal allergy testing-directed food avoidance paved the way for empirical elimination diets. These are moderately effective and highly reproducible in inducing EoE remission and allow for identification of specific food triggers. Step-up strategies, including two- and four-food rather than six-food elimination diets, should be considered as initial approaches for dietary treatment in patients of all ages, as they reduce the need for endoscopic procedures, shorten diagnostic processing time, and avoid unnecessary restrictions. Formulations of STC originally designed for asthma therapy are suboptimal for EoE treatment, with new effervescent orodispersible tablets and viscose formulations designed to coat the esophageal mucosa providing increased effectiveness at reduced doses. The anti-inflammatory effects of PPI in EoE are independent from gastric acid secretion inhibition; despite evidence from observational research, PPIs are the most commonly prescribed first-line therapy for EoE due to their accessibility, low cost, and safety profile. Double doses of PPI only induce remission in half of EoE patients, irrespective of the drug used or patients’ age. Inflammatory rather than stricturing EoE phenotype and treatment duration up to 12 weeks increase chances of achieving EoE remission. Most responders effectively maintain long-term remission with standard PPI doses. Finally, endoscopic dilation should be considered in patients with reduced esophageal caliber or persistent dysphagia despite histological remission. This article provides a state-of-the-art review and updated discussion of current therapies and newly developed options for EoE.

Analysis of Unused and Expired Medication Collected through Home Pharmaceutical Care Service

Unused and expired medications (UEM) have been reported to induce environmental pollution and financial loss of health insurance. This study aimed to actively collect and analyze the characteristics of UEM stored at home by patients through a home pharmaceutical care service. The study was conducted from July 16 to December 20, 2020. The subjects were patients who had one or more of the 13 typical chronic diseases and took ten or more drugs regularly. We analyzed the characteristics of the study subjects and the characteristics of the collected UEM. The results showed that the incidence rate of UEM was 60.5% (n=141), among all subjects (n=233), the number of prescription medicine taken per subject was about 17.10(±9.71), the total number of UEM per subject was 108.84(±144.82), and the number of therapeutic class for UEM per subject was 8.36(±8.81). The total cost of UEM per subject reached 38,205.53(±58,150.31) won (&#8361;). As for the collected UEM, gastrointestinal tract-related drugs such as gastrointestinal motility regulators and gastric acid secretion inhibitors were the most common. There was a statistically significant correlation between the number of prescription drugs in use and the total number of UEM (p=0.039). In conclusion, active collection of UEM through home pharmaceutical care service showed better results than the passive collection. The findings of this study are expected to contribute to the proper management of UEM.

Proton pump inhibitors interfere with the anti-tumor potency of RC48ADC

Antibody-drug conjugates (ADCs) are a promising modality for cancers, but the interaction between them and proton pump inhibitors (PPIs), the common adjuvant drugs for cancer treatment, has not been understood. Here, the interactions between PPIs and RC48ADC, a novel HER2-targeting ADC, were quantified in vitro. CCK-8 assay showed that RC48ADC displayed a significant inhibitory effect on the proliferation of SK-BR-3, NCI-N87 and SK-OV-3 cells with the IC50 values of 4.91 ± 1.15 ng/mL, 14.54 ± 0.85 ng/mL and 11.28 ± 0.68 ng/mL respectively. PPIs alone had no significant anti-tumor effect in the dose range of 1.37–1000 ng/mL. When used together, PPIs inhibited the anti-tumor activity of RC48ADC in a dose-dependent manner. And 1000 ng/mL (~Cmax) PPIs significantly recovered RC48ADC-inhibited cell proliferation by (32.85 ± 2.81) % (p < 0.05). However, cimetidine, a non-PPIs gastric acid secretion inhibitor, had no significant inhibitory effect on RC48ADC. Furthermore, omeprazole, rather than cimetidine, significantly reduced the activity of vacuolar H+-ATPase and Cathepsin B compared with the control cells. These results, if confirmed in vivo, indicate that PPIs are antagonists of RC48ADC, even all ADCs, appearing to be due to inhibition of vacuolar H+-ATPase activity. Moreover, cimetidine combined with ADCs instead of PPIs can prevent an adverse drug interaction.

Effect of a proton-pump inhibitor on intestinal microbiota in patients taking low-dose aspirin.

Low-dose aspirin (LDA) administration prevents cerebral infarction and myocardial infarction, but many studies found an association with mucosal injury. Proton-pump inhibitors (PPIs) can prevent gastric and duodenal mucosal damage, but they may exacerbate small-intestinal mucosal injury by altering the microbiota. We aimed to assess the effect of PPIs on the intestinal flora of LDA users. Thirty-two recruited patients, who received LDA (100mg/day) but did not take PPIs, were divided into 15 patients additionally receiving esomeprazole (20mg/day) and 17 patients additionally receiving vonoprazan (10mg/day). On days 0, 30, 90, and 180, the microbiota of each patient was examined by terminal restriction fragment length polymorphism analysis, and the serum gastrin, hemoglobin, and hematocrit levels were measured. Additional PPI administration increased the proportion of Lactobacillales in the microbiota of LDA users. This trend was more prevalent in the vonoprazan group (p < 0.0001) than in the esomeprazole group (p = 0.0024). The Lactobacillales proportion was positively correlated with the gastrin level (r = 0.5354). No significant hemoglobin or hematocrit level reduction was observed in subjects receiving LDA with additional PPI. Additional PPI administration increased the Lactobacillales proportion in the microbiota of LDA users. The positive correlation between the gastrin level and the proportion of Lactobacillales suggested that the change in the intestinal flora was associated with the degree of suppression of gastric acid secretion. Additional oral PPI did not significantly promote anemia, but the risk of causing PPI-induced small-intestinal mucosal injury in LDA users should be considered.

Prescribing Pattern of Drugs in Department of Obstetrics and Gynecology at A Tertiary Care Teaching Hospital, Bangalore, India

Objective: To assess the drug prescription pattern in the department of obstetrics and gynecology At A Tertiary Care Teaching Hospital, Bangalore, India. Methodology: A prospective observational study on Drug Utilization pattern was done in the department of Obstetrics and Gynecology of a 950 bedded tertiary care teaching hospital in Bangalore for 6 months. All patients were admitted to the Department of Obstetrics and Gynecology. Patients satisfying Inclusion criteria were enrolled after obtaining Informed Consent. Patient data entered into Case Report Form (CRF). Medication orders were observed for Prescription patterns. WHO Prescription indicators will be used to study the number of drugs per encounter, percentage of drugs prescribed by generic name, percentage of encounters with an antibiotic, percentage of encounters with an injection, percentage of drugs prescribed. Result: A total of 120 cases were collected. A total of 1004 drugs were prescribed which included 244 (24.30%) minerals and vitamin supplements, 219 (21.81%) Antibiotics, 146 (14.55%) Gastric acid Secretion Inhibitors, 108(10.75%) Analgesics, 35 (3.49%) Antihypertensive drugs, 22 (2.19%)Antifungal drugs, 32 (3.19%) Anti-diabetic drugs, 32 (3.19%) Anti-spasmodic, 41 (4.08%) Antiemetic drugs, 12 (1.19%) Corticosteroids, 16 (1.59%) Anticonvulsant drugs, 97 (9.66%) in the category of “Others”: Anti sceptics, Topical agents, Oxytocic, Antihyperlipidemic drugs, Oral contraceptives, etc. Percentage of Drugs used in different categories were, In our study majority of drugs from Category A (45.405), Category B (35.63%), Category C (16.67%), Category D (2.30%). the average number of drugs per prescription in this study (8.36) is higher than the standard set by WHO (1.6-1.8), percentage of patients prescribed with Injectables is 39.70% this is also high when compared with the range of the standard set by WHO. Conclusion: The results of our study highlight several areas that need improvement, most importantly there is Polypharmacy was practiced as the average number of drugs (8.36) per prescription when compared with a standard set by WHO. Another area that is Percentage of drugs prescribed by Generic name is also low which also need to improve. Iron, Calcium, and Folic acid were the most frequently prescribed drugs. Overall drug use pattern is rational with few exceptions which were mentioned above. The majority of the drugs were prescribed from the Essential Medicine List and the majority of drugs were prescribed as per FDA Category A the Safest Category during pregnancy. Keywords: prescription pattern, Obstetrics, Gynecology

Long-term vonoprazan therapy is effective for controlling symptomatic proton pump inhibitor-resistant gastroesophageal reflux disease.

Vonoprazan, a novel potassium-competitive acid blocker, results in greater inhibition of gastric acid secretion than proton pump inhibitors (PPI). The aim of this study was to assess the long-term outcomes of patients with PPI-resistant gastroesophageal reflux disease (GERD) treated with vonoprazan. The medical records of patients with symptomatic GERD treated with vonoprazan for 1 year were retrospectively reviewed. Changes in abdominal symptoms were assessed using the Izumo scale, a self-reported questionnaire which is useful in evaluating the symptoms of GERD, epigastric pain, postprandial distress, constipation and diarrhea, and is commonly used in routine clinical practice. A total of 30 patients were included and stratified into a non-erosive (n=22) and erosive group (n=8). At baseline, postprandial distress symptoms were significantly greater in the non-erosive group compared with the erosive group (P=0.013). Even with vonoprazan therapy, symptoms of GERD in the non-erosive group were refractory compared with the erosive group, and required additional treatment in a larger proportion of patients (45 vs. 13%). GERD symptoms in the non-erosive group significantly improved from baseline and remained better after 1 year of vonoprazan therapy, similar to the erosive group. In addition, vonoprazan improved epigastric pain and postprandial distress symptoms in the non-erosive group, and 1 year of vonoprazan therapy did not aggravate constipation or diarrhea. In conclusion, 1 year of vonoprazan therapy improves GERD symptoms in patients with PPI-resistant GERD.

Proton Pump Inhibitors and Primary Liver Cancer

During the last years proton pump inhibitors (PPIs), previously regarded as very safe drugs and allowed to be sold over the counter, have been reported to give side effects in many organ systems. However, most of these negative reports probably are due to residual confounding factors. In general, the side effects of PPIs are due to their biological effect in removing the biological effect of gastric juice that is killing microorganisms, and the secondary hypergastrinemia in an unsuccessful attempt to restore normal gastric acidity. Whereas the possibility that hypergastrinemia could predispose to gastric cancer has been permanently on the agenda since the introduction of PPIs, the removal of the important protective effect towards microbes has surprisingly only been focused on during the later years as a consequence of increased interest on the gut microbiome. PPI treatment affects the microbiome, and it exists one report describing increased risk of primary liver cancer due to PPI use. Changes in the gut microbiome have been shown to participate in the pathogenesis of chronic liver diseases caused by ethanol as well as obesity. In general, chronic liver diseases predispose to liver cancer. There are also rodent studies incriminating inhibition of gastric acid secretion in the pathogenesis of primary liver cancer. However, it must be concluded that presently the role of PPIs in the development of primary liver cancer seems weak.

High Body Mass Index Is Correlated with the Success of Vonoprazan-Based Second-Line Therapy for Helicobacter Pylori Infection.

Eradication of Helicobacter pylori (Hp) is necessary for preventing peptic ulcers and stomach cancer. The potassium-competitive acid blocker vonoprazan is a gastric acid secretion inhibitor that improves the success rate of Hp eradication through its immediate and persistent inhibition of acid excretion. In Japan, first-line treatment involves a regimen in which vonoprazan is combined with amoxicillin and clarithromycin, while second-line treatment involves vonoprazan combined with amoxicillin and metronidazole. However, in contrast to the vonoprazan-based first-line therapy, no studies have investigated the factors influencing the success of vonoprazan-based second-line therapy. In this study, we therefore aimed to investigate factors related to the success of vonoprazan-based second-line therapy. We analyzed the association between the success of Hp eradication and patient factors including metronidazole/amoxicillin minimal inhibitory concentrations (MICs). MICs were measured using the Hp isolated from each patient. A receiver operating characteristic (ROC) analysis was conducted to examine continuous variables and eradication success. We reviewed the records of 33 patients (age: 34-79 years, male/female: 22/11, and body mass index (BMI): 16.1-28.8 kg/m2) who underwent vonoprazan-based second-line therapy after failure of first-line therapy at seven Japanese facilities between October 2018 and June 2019. The eradication success rate was 81.8% (27/33). ROC analysis revealed an area under the curve and BMI cutoff value of 0.796 and 23.8 kg/m2, respectively. The eradication success rate was higher in patients with high BMI than in those with low BMI (p = 0.007). Our findings indicate that higher BMI is correlated with the success of vonoprazan-based second-line therapy.

Proton pump inhibitors for the treatment of laryngopharyngeal reflux disease: A protocol for systematic review and meta-analysis.

Background:Laryngopharyngeal Reflux disease refers to abnormal reflux of gastric contents through the esophagus into the throat, which irritates and damages the pharyngeal mucosa, and causes corresponding symptoms. Proton Pump Inhibitors are an important class of gastric acid secretion inhibitors after H2 receptor blockers, which can be used clinically to treat peptic ulcer, abnormal gastric acid secretion and other related diseases. The common clinical drugs include omeprazole, lansoprazole, rabeprazole and so on. Clinical practice has shown that Proton Pump Inhibitors have a good therapeutic effect on Laryngopharyngeal Reflux disease, but evidence of evidence-based medicine is lacking. The purpose of this protocol is to systematically evaluate the efficacy and safety of Proton Pump Inhibitors in the treatment of Laryngopharyngeal Reflux disease and to improve the evidence-based basis for the clinical application of Proton Pump Inhibitors in the treatment of Laryngopharyngeal Reflux disease.Methods:English computer retrieval database (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese computer retrieval database (Wanfang Database, VIP Information Chinese Journal Service Platform, Chinese Biomedical Database) . In addition, Baidu Scholar and Google Scholar were manually searched for randomized controlled clinical studies on the treatment of laryngeal reflux disease with Proton Pump Inhibitors from the establishment of the database to July 2020. Two researchers independently extracted and evaluated the data of the included studies, and meta-analysis was conducted on the included literatures with RevMan5.3 software without language restrictions.Results:In this study, the efficacy and safety of Proton Pump Inhibitors in the treatment of Laryngopharyngeal Reflux disease are evaluated by the overall response rate, clinical symptom remission rate and other indicators.Conclusions:This study will provide reliable evidence-based evidence for the clinical application of Proton Pump Inhibitors in the treatment of Laryngopharyngeal Reflux disease.OSF Registration number: DOI 10.17605 / OSF.IO / NY6SC

Vonoprazan vs lansoprazole for the treatment of artificial gastric ulcer after endoscopic submucosal dissection: a prospective randomized comparative study.

Vonoprazan is a potent inhibitor of gastric acid secretion and may have better response than proton pump inhibitors (PPIs) in the treatment of endoscopic submucosal dissection induced artificial ulcers. However, reported outcomes remain controversial. In this study, we conducted a prospective, randomized comparative trial to evaluate healing effects of vonoprazan and lansoprazole on endoscopic submucosal dissection (ESD)-induced ulcers. We enrolled 216 patients who underwent endoscopic submucosal dissection for early gastric neoplasms. They were randomly divided into vonoprazan (20 mg/day) and lansoprazole (30 mg/day) groups. The primary endpoint was the reduction rate of ulcer and complete healing (scar) ratio of ESD-induced ulcers at 4 and 8 weeks. Finally, 101 patients of the vonoprazan group and 95 patients of the lansoprazole group were included in the analysis. There were no significant differences in the reduction rate between the vonoprazan and lansoprazole groups at either timepoint (4 weeks, 94.0 vs 93.4%; 8 weeks, 99.8 vs 99.9%, respectively). The complete healing ratio at 4 and 8 weeks did not differ significantly between the vonoprazan and lansoprazole groups (4 weeks, 11.9 vs 12.6%; 8 weeks, 87.1 vs 86.3%, respectively). In the anti-H. pylori-antibody negative or positive patients, there were no significant differences in the reduction rate and complete healing ratio between the vonoprazan and lansoprazole groups. Regardless of treatment choice, the overall complete healing ratio at 8 weeks was significantly higher in the anti-H. pylori-antibody negative patients than the positive patients (p = 0.006). The healing effects of vonoprazan on ESD-induced ulcers were comparative to those of lansoprazole.

Suppression of gastric acid secretion decreased cardiovascular events independent of severe bleeding events in patients after percutaneous coronary intervention – sub-analysis from multicenter registry

Abstract Background Suppression of gastric acid secretion by proton-pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) has recently been developed as a standard strategy for preventing gastrointestinal bleeding for patients receiving antiplatelet therapy after percutaneous coronary intervention (PCI). However, there has been limited evidences on the association between PPI/P-CAB administration and adverse cardiovascular events in patients undergoing PCI. Purpose We aimed to evaluate the prognostic impact of the prescription of PPI/P-CAB on clinical outcomes in patients after PCI. Methods This study is a subanalysis from the TWINCRE registry that is a multicentral prospective cohort including patients who underwent PCI at 12 hospitals in Japan between 2017 and 2019. Among registered patients, we ultimately evaluated 1,428 patients who were followed-up. They were divided into two groups by the prescriptions of PPI or P-CAB at discharge for the index PCI; the PPI/P-CAB group (n=1,023), and the Non-PPI/P-CAB group (n=407). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE) including death, acute coronary syndrome, stent thrombosis, hospitalization due to heart failure and ischemic stroke. Secondary endpoints was major bleeding events defined BARC3, 4 and 5. Results The average age of the study population was 70.3 years and 80.3% were male. Baseline clinical profiles were comparable between the groups, except that the PPI/P-CAB group included significantly higher rate of patients who had history of prior PCI (28.4% vs 18.7%, P=0.02). Additionally, there was no significant difference in the duration of dual antiplatelet therapy between the PPI/P-CAB group and Non-PPI/P-CAB group (average duration; 287±8 vs. 285±8 days, P=0.66). Overall, MACCE was developed in 132 patients (9.3%), and bleeding event was observed in 24 patients (1.7%) during 574 days of median follow-up period. Kaplan-Meier analysis showed that patients in the PPI/P-CAB group had a significantly lower rate of MACCE than those in the Non-PPI/P-CAB group (Log-rank test, p=0.0003, Figure 1A). Multivariate Cox regression analysis revealed that the prescription of PPI/P-CAB still was independently associated with the primary endpoint (hazard ratio 0.532, 95% confidence interval 0.369–0.766, p=0.0007), even after the adjustment by diverse covariates. Whereas, there was no significant difference in the bleeding event (p=0.64, Figure 1B). Conclusion PPI or P-CAB therapy was associated with better clinical outcomes after PCI, independent of the incidences of severe bleeding events. Figure 1 Funding Acknowledgement Type of funding source: None