Standard-dose Proton Pump Inhibitors Research Articles

Current status and influencing factors of prophylactic use of proton pump inhibitors in internal medicine inpatients receiving glucocorticoid therapy.

The actual situation and influencing factors of prophylactic use of proton pump inhibitors (PPIs) in internal medicine inpatients receiving glucocorticoid therapy are rarely reported. This study aimed to investigate the current status and influencing factors of prophylactic use of PPIs in internal medicine inpatients receiving glucocorticoid therapy to provide a basis for rational prophylactic use of PPIs. Internal medicine inpatients receiving glucocorticoid therapy from February 2023 to September 2023 were included. Information on the prophylactic use of PPIs was collected and analyzed by clinical pharmacists. Associated factors with prophylactic use of PPIs were analyzed by univariable and multivariable logistic regression. 980 inpatients were finally included in our study, of which 271 (27.7%) inpatients received prophylactic use of PPIs. Among the inpatients prescribed PPIs, 90 inpatients received a standard dose of PPIs twice a day. Multiple logistic regression analysis showed that age ≥80years [OR = 7.009, 95% CI (1.424, 34.495), p = 0.017], history of gastroesophageal reflux disease (GERD) [OR = 2.047, 95% CI (1.338, 3.133), p = 0.001], low platelet count [OR = 0.997, 95% CI (0.994, 0.999), p = 0.004], number of concomitant diseases [OR = 1.104, 95% CI (1.056, 1.153), p < 0.001], junior doctors [OR = 1.755, 95% CI (1.248, 2.468), p = 0.001], glucocorticoid dose (higher than 50mg, measured by methylprednisolone) [OR = 2.455, 95% CI (1.371, 4.395), p = 0.003], antiplatelet agents [OR = 2.567, 95% CI (1.456, 4.524), p = 0.001], immunosuppressants [OR = 1.477, 95% CI (1.014, 2.153), p = 0.042], and betahistine [OR = 5.503, 95% CI (1.124, 26.950), p = 0.035] were associated with more prophylactic use of PPIs. The prophylactic use of PPIs in internal medicine inpatients receiving glucocorticoid therapy is common in China. Clinical pharmacists will take targeted measures to promote the rational use of PPIs according to the results of this study.

Clinical progression of parotid salivary gland sialadenosis based on the selected &lt;i&gt;H. pylori&lt;/i&gt; eradication therapy

Relevance. In approximately 50.82% of instances, sialadenosis of the parotid salivary gland (PSG) emerges as a sequel to gastrointestinal (GI) disorders. This condition is characterized by diminished saliva production (hyposalivation) and enlargement (hypertrophy) of the gland. In Russia, the prevalence of GI diseases linked to acid-related issues and H. pylori infection (HP) is notably high. The therapeutic approach to this pathology focuses on the eradication of HP, employing various treatment strategies that incorporate the use of a proton pump inhibitor (PPI). The efficacy of PPIs hinges on their ability to inhibit the proton pump, which is situated in the endothelial lining of the smooth muscle vessels, including those that encase the acinar cells of the PSG. An essential aspect of parotid secretion is its protective role, which is executed through the production of secretory immunoglobulin A (sIgA) within the gland's ductal system. Therefore, exploring the clinical progression of PSG sialadenosis under eradication therapy regimens holds substantial significance.Materials and methods. Between 2021 and 2023, 80 patients with parotid salivary gland (PSG) sialadenosis and Helicobacter pylori stomach infection were studied. They were divided into treatment groups: Group I (25 patients, aged 45.81 ± 6.39 years) received quadruple therapy (standard-dose PPI, amoxicillin 1,000 mg, clarithromycin 500 mg twice daily, and bismuthate tripotassium dicitrate 120 mg four times daily); Group II (55 patients, aged 47.79 ± 7.15 years) underwent standard triple therapy (double-dose PPI, amoxicillin 1,000 mg, and clarithromycin 500 mg twice daily). A control group consisted of 20 nearly healthy individuals (average age 26.46 ± 4.12 years). All subjects underwent comprehensive dental and PSG assessments, including questionnaires, sialometry, and measurement of (sIgA) levels in parotid secretion.Results. After eradication therapy, Group I patients treated with quadruple therapy exhibited a 1.2-fold reduction in PSG secretory function (p = 0.048) and a 1.2-fold decrease in sIgA concentration (p = 0.035) compared to initial levels. Group II patients receiving triple therapy demonstrated a significant 3.6-fold decline in PSG sialometry parameters (p = 0.002) and a 1.8-fold reduction in sIgA levels (p = 0.006) by the 14th day post-eradication, relative to pre-treatment figures. Conclusion. Therefore, patients with GI acid-related conditions linked to HP infection should be evaluated by a dentist for potential PSG sialadenosis. The presence of PSG sialadenosis in individuals with HP stomach infection warrants consideration in the selection and administration of eradication therapy.

Twice-Daily Proton Pump Inhibitor Induces Higher Remission Rate in Eosinophilic Esophagitis Than Once-Daily Regimen Regardless of Total Daily Dose.

The optimal proton pump inhibitor (PPI) regimen for eosinophilic esophagitis (EoE) is unclear. We compared histologic response rates of different dosing combinations. A total of 305 patients with newly diagnosed EoE received standard (omeprazole 20 mg daily), once-daily moderate (40 mg daily), twice-daily moderate (20 mg twice daily), or high (40 mg twice daily) dose PPI for ≥8 weeks. Approximately 42.3% achieved histologic response to PPI, with higher rates for twice-daily (moderate 52.8%/high 54.3%) than once-daily (standard 11.8%/moderate 10%) dosing ( P < 0.0001). On multivariable analysis, twice-daily moderate (adjusted odds ratio 6.75, confidence interval 2.53-18.0, P = 0.0008) and high (adjusted odds ratio 12.8, confidence interval 4.69-34.8, P < 0.0001) doses independently predicted histologic response. Twice-daily PPI is associated with higher EoE histologic response rates than once-daily regimen.

Prevalence and risk factors for medication-refractory reflux esophagitis in patients with systemic sclerosis in Japan.

Patients with systemic sclerosis (SSc) often have esophageal motility abnormalities and weak esophago-gastric junction (EGJ) barrier function, which causes proton pump inhibitor (PPI)-refractory reflux esophagitis (RE). The aims of this study were to clarify the current management of RE and prevalence and risk factors of medication-refractory RE in patients with SSc in Japan. A total of 188 consecutive patients with SSc who underwent both esophageal high-resolution manometry (HRM) and esophagogastroduodenoscopy (EGD) were reviewed. The presence of RE and grades of the gastroesophageal flap valve (GEFV) were assessed. Esophageal motility was assessed retrospectively according to the Chicago classification v3.0. When RE was seen on a standard dose of PPI or any dose of vonoprazan (VPZ), it was defined as medication-refractory RE. Approximately 80% of patients received maintenance therapy with acid secretion inhibitors regardless of esophageal motility abnormalities. Approximately 50% of patients received maintenance therapy with PPI, and approximately 30% of patients received VPZ. Medication-refractory RE was observed in 30 patients (16.0%). In multivariable analyses, the number of EGD and absent contractility were significant risk factors for medication-refractory RE. Furthermore, combined absent contractility and GEFV grade III or IV had higher odds ratios than did absent contractility alone. Patients with persistent reflux symptoms and those with absent contractility and GEFV grade III or IV should receive maintenance therapy with strong acid inhibition to prevent medication-refractory RE.

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

Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication. 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). 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. 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 10days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness. 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.

On-demand Versus Continuous Maintenance Treatment With a Proton Pump Inhibitor for Mild Gastroesophageal Reflux Disease: A Prospective Randomized Multicenter Study.

It remains unclear which maintenance treatment modality is most appropriate for mild gastroesophageal reflux disease (GERD). We aimed to compare on-demand treatment with continuous treatment using a proton pump inhibitor (PPI) in the maintenance treatment for patients with non-erosive GERD or mild erosive esophagitis. Patients whose GERD symptoms improved after 4 weeks of standard dose PPI treatment were prospectively enrolled at 25 hospitals. Subsequently, the enrolled patients were randomly assigned to either an on-demand or a continuous maintenance treatment group, and followed in an 8-week interval for up to 24 weeks. A total of 304 patients were randomized to maintenance treatment (continuous, n = 151 vs on-demand, n = 153). The primary outcome, the overall proportion of unwillingness to continue the assigned maintenance treatment modality, failed to confirm the non-inferiority of on-demand treatment (45.9%) compared to continuous treatment (36.1%). Compared with the on-demand group, the GERD symptom and health-related quality of life scores significantly more improved and the overall satisfaction score was significantly higher in the continuous treatment group, particularly at week 8 and week 16 of maintenance treatment. Work impairment scores were not different in the 2 groups, but the prescription cost was less in the on-demand group. Serum gastrin levels significantly elevated in the continuous treatment group, but not in the on-demand group. Continuous treatment seems to be more appropriate for the initial maintenance treatment of non-erosive GERD or mild erosive esophagitis than on-demand treatment. Stepping down to on-demand treatment needs to be considered after a sufficient period of continuous treatment.

Multicentre prospective study to evaluate effectiveness and safety of gel-forming and hyaluronic-acid containing chewable tablets as add-on treatment in patients with gastroesophageal reflux disease (GERD) symptoms and unsatisfying proton pump inhibitor therapy

BackgroundGastroesophageal reflux disease (GERD) is a common disease which in the majority of patients is treated with proton pump inhibitors (PPI). However, up to 45% of the patients remain symptomatic on a standard dose of PPI. This study investigated the effectiveness and safety of an add-on therapy with the gel-forming chewable tablet Sobrade® in patients unsatisfied with PPI treatment. The bioadhesive gel covers the oesophagus and thereby protects the mucosa from reflux events.Methods47 patients with symptomatic GERD despite PPI treatment participated in this study. The gel-forming tablets were taken up to four times daily after meals and prior to bedtime. Severity and frequency of GERD symptoms were evaluated during two onsite visits prior and following 14 days of treatment and used to calculate the GERD score of the Reflux Disease Questionnaire. Furthermore, patients recorded symptoms as well as onset and duration of symptoms relief daily in their electronic dairies. Effectiveness of treatment was analysed using non-parametric paired Wilcoxon test. In addition, anchor-based minimal important differences (MID) were assessed.ResultsTreatment resulted in significant reduction of GERD symptoms. Severity and frequency of 8 of the 9 assessed symptoms improved significantly during the treatment phase whereby most pronounced improvement was observed for heartburn. In agreement, all three subscales of the GERD score improved significantly. MID results suggest that patients considered a mean improvement of symptoms > 30% of initial severity as beneficial. Self-assessments by patients revealed first significant improvements of symptoms like heartburn and regurgitation from day 5 of treatment onwards. 49% of patients reported relief of symptoms within 15 min which lasted on average for 3.5 h. During the study no treatment emergent adverse events were reported and in 98% of all cases tolerability of the product was rated as very good or good.ConclusionsThis study revealed a pronounced improvement of the symptoms after add-on treatment with the gel-forming medical device. The very good safety and tolerability profile indicate an advantageous risk-benefit ratio.Trial registrationThis non-interventional study was prospectively positively evaluated by the responsible ethic-committees.

Relevance of Excessive Air Swallowing in GERD Patients With Concomitant Functional Dyspepsia and Poor Response to PPI Therapy.

The present study was aimed at evaluating the possible role of air swallowing in the association between gastroesophageal reflux disease (GERD) symptoms and concomitant functional dyspepsia (FD) and their role in GERD symptom persistence despite proton pump inhibitor (PPI) therapy. It has been shown that individuals with excessive air swallowing experience FD. It has been also demonstrated that a consistent group of GERD patients not responding to PPI therapy swallow more air during mealtime and also have more mixed refluxes. Multichannel intraluminal impedance-pH tracings from consecutive patients were retrospectively evaluated. A validated structured questionnaire was used to evaluate GERD and concomitant FD symptoms. All patients were treated, within the previous year, with at least 8 weeks of standard-dose PPI therapy. A total of 35 patients with conclusive GERD, 35 patients with reflux hypersensitivity, and 35 with functional heartburn were studied. A direct relationship was observed between the number of air swallows and of mixed refluxes ( R =0.64). At receiver operating characteristic curve analysis, air swallows and mixed refluxes were significantly associated to the presence of FD and PPI refractoriness. An air swallow cutoff of 107 episodes/24 hours was identified to discriminate patients with and without FD (sensitivity: 87%, specificity: 82.8%). A mixed reflux cutoff of 34 episodes/24 hours was identified to discriminate PPI responders from nonresponders (sensitivity: 84.8%, specificity: 69%). At multivariate analysis, an abnormal number of air swallows and of mixed refluxes were significantly associated to FD and PPI refractoriness. Our study highlights the relevant role of excessive air swallowing in eliciting both dyspepsia and refractoriness of typical GERD symptoms to PPI therapy.

Efficacy and safety of proton pump inhibitors versus vonoprazan in treatment of erosive esophagitis: A PRISMA-compliant systematic review and network meta-analysis.

Proton-pump inhibitors (PPIs) and vonoprazan are recommended as first-line therapies for erosive esophagitis (EE). However, it is uncertain how the magnitude of efficacy and safety of first-line therapy, the choice of individual PPIs or vonoprazan in the treatment of EE remains controversial. This study aimed to evaluate the efficacy and safety of vonoprazan and PPIs in healing esophageal mucosal injury in patients with EE. Relevant databases were searched to collect randomized controlled trials of proton pump inhibitors and vonoprazan in the treatment of reflux esophagitis up to December 2021. Studies on standard-dose PPIs or vonoprazan that were published in Chinese or English and assessed healing effects in EE were included in the analysis. Stata16.0 was used to conduct a network Meta-analysis to evaluate the efficacy and safety of the treatment. A total of 41 literatures were included with 11,592 enrolled patients. For the endoscopic cure rate, all the PPIs and vonoprazan significantly improve compared to Placebo; Based on the surface under the cumulative ranking curve, Ilaprazole ranked first, followed by esomeprazole, vonoprazan, pantoprazole, lansoprazole, omeprazole, rabeprazole and placebo therapy ranked the last. For the rate of adverse events, there was no significant difference among all the PPIs, vonoprazan, and placebo. Ilaprazole, esomeprazole and vonoprazan have more advantages in mucosal erosion healing, there was no significant difference in the comparative safety among all interventions.

Impact of insufficient doses of medications on Helicobacter pylori eradication: a retrospective observational study

Background and aims The doses of medications may influence the success of Helicobacter pylori (H. pylori) eradication. This real-world observational study aimed to explore the impact of insufficient doses of medications prescribed for the bismuth-containing quadruple therapy (BQT) regimen on successful H. pylori eradication. Methods We retrospectively screened the patients who were diagnosed with H. pylori infection and received BQT regimens for H. pylori eradication at our department between January 2017 and July 2020. The rate of successful H. pylori eradication was compared according to the doses of medications prescribed. Standard doses were defined according to the clinical guidelines. Results Overall, 1054 patients were included. The rate of successful H. pylori eradication was 78.2% (824/1054). Among them, proton pump inhibitors (PPIs) and antibiotics were prescribed at insufficient doses in 37.0% (390/1054) and 6.7% (71/1054) of patients, respectively. Furthermore, pantoprazole (98.7% [385/390]) was the most common type of PPIs prescribed at insufficient doses, and nitroimidazoles (85.9% [61/71]) were the most common type of antibiotics prescribed at insufficient doses. Among the patients receiving colloidal bismuth pectin (CBP) (200mg tid) and standard-dose antibiotics, the rate of successful H. pylori eradication was lower in insufficient-dose PPIs group than standard-dose PPIs group (78.1% [271/347] versus 82.6% [438/530], P=0.095). Among the patients receiving CBP (200mg tid) and standard-dose PPIs, the rate of successful H. pylori eradication was significantly lower in insufficient-dose antibiotics group than standard-dose antibiotics group (37.8% [14/37] versus 82.6% [438/530], P<0.0001). Among the patients receiving CBP 200mg tid, the rate of successful H. pylori eradication was significantly lower in patients receiving both PPIs and antibiotics at insufficient doses than those at standard doses (46.4% [13/28] versus 82.6% [438/530], P<0.0001). Conclusion Among the BQT regimens, PPIs and/or antibiotics, especially pantoprazole and metronidazole, are often prescribed at insufficient doses, compromising the success of H. pylori eradication.

Hypercontractile esophagus responsive to potassium-competitive acid blockers: a case report

BackgroundHypercontractile esophagus is a rare hypercontractile esophageal motility disorder. The etiology of hypercontractile esophagus is unknown but an association between acid reflux and hypercontractile esophagus has been suggested. We present the first report on the use of potassium-competitive acid blockers in the treatment of hypercontractile esophagus.Case presentationA 43-year-old man presented with dysphagia, chest pain and regurgitation for a period of 1 year. Initial workup showed a twisted lumen with abnormal contractions in the distal esophagus during upper gastrointestinal endoscopy and abnormal acid exposure under 24-h esophageal pH monitoring. The use of standard-dose proton pump inhibitors didn’t relieve his symptoms. Subsequent high-resolution esophageal manometry made a diagnosis of hypercontractile esophagus. Treatment with vonoprazan resulted in symptomatic resolution and abnormal contractions were no longer detected on follow-up high-resolution manometry.ConclusionsPotassium-competitive acid blockers like vonoprazan offer an alternative therapeutic method for patients with hypercontractile esophagus who are refractory to proton pump inhibitor therapy. The use of potassium-competitive acid blockers in hypercontractile esophagus warrants further research and may provide evidence for an acid-related etiology of hypercontractile esophagus.

Gastroesophageal reflux disease: new approaches to optimizing pharmacotherapy

Proton pump inhibitors (PPIs) are baseline drugs for induction and maintenance of remission in gastroesophageal reflux disease (GERD). PPIs have proven to be highly effective in healing esophageal mucosal lesions and relieving the symptoms of the disease in most cases. However, according to the literature data, the incidence rate of clinical ineffectiveness of PPIs in the form of partial or complete persistence of current symptoms during administration of standard doses of PPIs ranges from 10 to 40%. Optimization of GERD therapy in PPI refractory patients is a significant challenge. In most cases, experts advise to increase a dose / dosage frequency of PPIs, switch to CYP2C19-independent PPIs (rabeprazole, esomeprazole, dexlansoprazole), add an esophagoprotective or promotility agents to therapy. At the same time, these recommendations have a limited effect in some patients, which opens up opportunities for looking for new solutions related to the optimization of GERD therapy. Today there is growing evidence of the relevance of the role of disruption of the cytoprotective and barrier properties of the esophageal mucosa in the genesis of GERD and the formation of refractoriness. Intercellular contacts ensure the integrity of the barrier function of the esophageal mucosa to protect it from various exogenous intraluminal substances with detergent properties. Acid-peptic attack in patients with GERD leads to alteration of the expression of some tight junction proteins in epithelial cells of the esophageal mucosa. The latter leads to increased mucosal permeability, which facilitates the penetration of hydrogen ions and other substances into the submucosal layer, where they stimulate the terminals of nerve fibers playing a role in the induction and persistence of the symptoms of the disease. The above evidence brought up to date the effectiveness study of the cytoprotective drugs with tropism to the gastrointestinal tract, as part of the combination therapy of GERD.

Efficacy of Vonoprazan for Refractory Reflux Esophagitis after Esophagectomy

Background: Refractory reflux esophagitis (RRE), unresponsive to conventional proton-pump inhibitors (PPIs), is a complication in esophagectomy with gastric pull-up. Vonoprazan (VPZ), a novel potassium-competitive acid blocker, has been available in Japan since 2015. Here, we investigated the efficacy of VPZ on PPI-resistant RRE after esophagectomy with gastric pull-up. Methods: This was a single-center retrospective study. We used the revised Los Angeles (r-LA) classification based on the Los Angeles classification and the modified Los Angeles classification to evaluate abnormal forms of mucosal breaks such as lateral spreading consistently. Patients who underwent esophagectomy with gastric pull-up and had RRE grade B–D as per the r-LA classification, despite using standard-dose PPIs or double dose of rabeprazole, were included. Sixteen patients who switched to VPZ (20 mg/day) and 14 patients who continued PPIs were assigned to the VPZ and PPI groups, respectively. Endoscopic observations were reviewed by 3 endoscopists using the r-LA classification to ensure consistent diagnosis, while the treatment arm and patient information were blinded to evaluators. We defined mucosal breaks that improved by at least one grade after treatment as improved mucosa and recovery to grade M or N as mucosal healing. Results: The percentage of patients with improved mucosa in the VPZ and PPI groups was 81.3 and 14.3%, respectively (p < 0.001). The rate of mucosal healing was 68.8 and 7.1%, respectively (p = 0.001). Conclusion: VPZ significantly improved PPI-resistant RRE after esophagectomy with gastric pull-up.

High-Dose Proton Pump Inhibitors Are Superior to Standard-Dose Proton Pump Inhibitors in High-Risk Patients With Bleeding Ulcers and High-Risk Stigmata After Endoscopic Hemostasis.

INTRODUCTION:To define the best cutoff of the Glasgow-Blatchford score (GBS) for identifying high- and low-risk rebleeding patients with bleeding ulcers and high-risk stigmata after endoscopic hemostasis and compare the efficacy of high-dose and standard-dose intravenous proton pump inhibitors (HD-IVPs and SD-IVPs, respectively) in this patient population.METHODS:We retrospectively reviewed the data of 346 patients with bleeding ulcers and high-risk stigmata who underwent endoscopic hemostasis between March 2014 and September 2018 in our center and were divided into an HD-IVP group and an SD-IVP group. Propensity score–matching analysis was performed to control for selection bias and other potential confounders. Recurrent bleeding rates were calculated according to the GBS.RESULTS:Overall, 346 patients meeting the inclusion criteria were enrolled, with 89 patients in the SD-IVP group and 89 patients in the HD-IVP group after matching with all baseline characteristics balanced (P > 0.05). GBS = 8 was the best cutoff for identifying high-risk rebleeding patients (GBS ≥ 8) with a significant difference (P = 0.015) in recurrence rate between the SD-IVP (17/61, 27.9%) and HD-IVP (7/65, 10.8%) groups and low-risk rebleeding patients (GBS < 8) with no difference (P = 1) in recurrence rate between the SD-IVP (2/28, 7.1%) and HD-IVP (2/24, 8.3%) groups.DISCUSSION:The best cutoff for identifying high-risk and low-risk rebleeding patients with bleeding ulcers and high-risk stigmata after endoscopic hemostasis was GBS = 8. Although HD-IVP is more effective than SD-IVP in high-risk patients, they are equally effective in low-risk patients.

Different dose of new generation proton pump inhibitors for the treatment of Helicobacter pylori infection: A meta-analysis.

The evidence on whether high-dose new generation proton pump inhibitors (PPIs) including rabeprazole and esomeprazole achieve a higher eradication rate of Helicobacter pylori has not been assessed. The primary comparison was eradication and adverse events (AEs) rate of standard (esomeprazole 20 mg bid, rabeprazole 10 mg bid) versus high-dose (esomeprazole 40 mg bid, rabeprazole 20 mg bid) PPIs. Sub-analyses were performed to evaluate the eradication rate between Asians and Caucasians, clarithromycin-resistance (CAM-R) strains, and clarithromycin-sensitivity (CAM-S) strains of different dose PPIs. We conducted a literature search for randomized controlled trials comparing high-with standard-dose esomeprazole and rabeprazole for H. pylori eradication and AEs. A total of 12 trials with 2237 patients were included. The eradication rate of high-dose PPIs was not significantly superior to standard-dose PPIs regimens: 85.3% versus 84.2%, OR 1.09 (0.86–1.37), P = 0.47. The high dose induced more AEs than those of the standard dose, but didn’t reach statistical significance (OR 1.25, 95% CI: 0.99–1.56, P = 0.06). Subgroup analysis showed that the difference in eradication rate of PPIs between high- and standard-dose groups were not statistically significant both in Asians (OR 0.99, 95% CI 0.75–1.32, P = 0.97) and Caucasians (OR 1.27, 95% CI 0.84–1.92, P = 0.26). Furthermore, there were similar eradication rates in CAM-S (OR 1.2; 95% CI 0.58–2.5; P = 0.63) and CAM-R strains (OR 1.08; 95% CI 0.45–2.56; P = 0.87) between the standard-and high-dose groups. High and standard dosages of new generation of the PPIs showed similar H. pylori eradication rates and AEs as well as between Asian versus Caucasian populations, with or without clarithromycin-resistance. However, further studies are needed to confirm.

Recommendations of the Russian Gastroenterological Association in Diagnosis and Treatment of Gastroesophageal Reflux Disease

Aim . Current recommendations of the Russian Gastroenterological Association are developed to acquaint medical practitioners with modern diagnostics, treatment and trends in rational drug therapy for gastroesophageal reflux disease (GERD). General provisions . Incidence rate of GERD in the Russian Federation varies from 11.3 to 23.6%. GERD is diagnosed with medical history and laboratory examination evidence. Esophagogastroduodenoscopy (EGDS) allows detection of reflux esophagitis of various severity and cylindrical epithelial metaplasia of esophagus. The refractory form of disease (lack of conclusive clinical and endoscopic remission during 4-8 weeks of standard-dose PPI therapy), presence of strictures and Barrett's esophagus require EGDS with esophageal biopsy and bioptic histological examination. Patients should be conclusively performed esophageal 24-hour pH-metry or pH-impedance monitoring, high-resolution manometry to thoroughly examine functionality of esophagus, esophagogastric junction and assess disease prognosis and therapy outcomes. Treatment of GERD should be personalised accounting for clinical manifestations and severity, as well as aimed at symptom improvement, lesion healing in erosive esophagitis, averting complications, Barrett's esophagus progression, dysplasia and esophageal adenocarcinoma. Proton pump inhibitors (PPIs) are most effective agents in primary (4-8 weeks) and maintenance anti-GERD therapy. Antacids are recommended in monotherapy for occasional nonerosive heartburn and complex anti-GERD settings for fast symptom improvement. Prokinetics can be used in combination with PPIs for their properties to recover normal functionality of esophagus through affecting pathogenetic mechanisms of GERD. Complicated patients (repeated bleedings, peptic esophageal strictures) are recommended anti-reflux surgery with prior examination of esophageal functionality using pH-impedance and high-resolution manometry. Conclusion . Current recommendations provide an up-to-date evidential medicial review of GERD and guidelines to advance special medical care and timely preventive measures.

High proton pump inhibitor exposure increases risk of calcinosis in systemic sclerosis

To investigate the association between proton pump inhibitor (PPI) use and the presence and severity of calcinosis in SSc. We analysed data from two SSc cohorts from a single centre. Cohort 1 included 199 patients reviewed over 10 years, for whom retrospective data on PPI use and calcinosis were available. Cohort 2 was recruited prospectively and included 215 consecutive patients, who underwent clinical assessment. Outcomes of interest were presence of current calcinosis (CC) or calcinosis at any time (CAT). The cohort 1 data analysis showed that among patients on standard dose PPI 20% had calcinosis, while in those on high doses of PPI calcinosis was present in 39% (P = 0.003). Analysis of the data from cohort 2 confirmed these findings, demonstrating that the odds of CAT increased significantly with longer PPI exposure [odds ratio (OR) 1.04, 95% CI: 1.02, 1.06; P < 0.001], longer disease duration (OR 1.08, 95% CI: 1.05, 1.12; P < 0.001) and greater age (OR 1.03, CI: 1.01, 1.05; P = 0.010). Multivariable logistic regression showed that higher exposure to PPI remained a significant predictor of calcinosis, with PPI exposure >10 years increasing the risk of CAT >6-fold, compared with no PPI (OR 6.37, 95% CI: 1.92, 21.17; P = 0.003) after adjusting for disease duration and antibodies. We confirm a significant association between high PPI exposure with severity of calcinosis in SSc. Given the clinical impact of calcinosis and reflux in SSc, PPI exposure as a potentially modifiable risk factor for calcinosis requires further evaluation.

Efficacy of a high-dose proton pump inhibitor in patients with gastroesophageal reflux disease: a single center, randomized, open-label trial

BackgroundThe extraesophageal manifestations of gastroesophageal reflux disease (GERD) are more difficult to manage than the typical symptoms. The efficacy of high-dose and standard-dose proton pump inhibitors against these atypical symptoms is not yet established.MethodsIn this single center, randomized, open-label study, patients with GERD received rabeprazole for 8 weeks, either 20 mg once daily (standard-dose group) or 20 mg twice daily (high-dose group). Patients were assessed before treatment and at weeks 4 and 8 with a 5-graded scale questionnaire consisting of 2 typical symptoms (heartburn and acid regurgitation) and 8 atypical symptoms (chest pain, cough, globus, wheezing, laryngopharyngitis, hoarseness, belching, and dysphagia). Sufficient improvement of reflux symptoms was defined as ≥50% reduction from the initial questionnaire score.ResultsFinal analyses included 35 patients in the standard-dose group and 38 patients in the high-dose group. The rate of sufficient improvement for typical symptoms was significantly higher in the high-dose group than in the standard-dose group (100.0% vs. 84.0%, P = 0.040). For atypical symptoms, the rate of sufficient improvement tended to be higher in the high-dose group than in the standard-dose group (82.4% vs. 63.0%, P = 0.087). Scores of typical and some atypical symptoms (cough and globus) improved after treatment, with significant inter-group differences in time-course changes.ConclusionsHigh-dose rabeprazole is more effective for relieving typical GERD symptoms and some atypical symptoms such as cough and globus than a standard-dose regimen.Trial registrationThis research was enrolled in a registry of clinical trials run by United States National Library of Medicine at the National Institutes of Health (ClinicalTrials.gov Protocol Registration and Results system ID: NCT04001400). This study was registered on June 26, 2019 - Retrospectively registered.

Association of residual gastric acid secretion with persistent symptoms in gastroesophageal reflux disease patients receiving standard-dose proton pump inhibitor therapy.

Although a third of gastroesophageal reflux disease (GERD) patients are refractory to proton pump inhibitor (PPI) therapy, the underlying mechanism of the refractoriness remains unclear. We compared the level of gastric acid suppression during PPI treatment between responders and non-responders by directly measuring gastric acid secretion in GERD patients taking PPIs. Seventy-five consecutive patients receiving standard-dose PPI therapy for GERD were prospectively recruited, irrespective of persistent GERD symptoms. They were asked about their GERD symptoms using a validated questionnaire, and simultaneously underwent both a routine endoscopic examination and a gastric acid secretory testing using an endoscopic gastrin test. Associations between residual gastric acid secretion during PPI treatment and persistent GERD symptoms were analyzed by a logistic regression analysis. Overall, 26 of 75 (34.7%) patients were judged to be positive for persistent GERD symptoms. The patients with and without persistent symptoms showed similar gastric acid secretion levels (1.3 [1.3]mEq/10min vs. 1.4 [2.0]mEq/10min). Sufficient gastric acid suppression, defined as < 0.6, was not significantly associated with persistent GERD symptoms (odds ratio 1.1, 95% confidence interval 0.40-3.5). This study provided solid evidence to support that the gastric acid suppression level during PPI treatment does not differ between patients with and without persistent GERD symptoms. The insignificant role of residual gastric acid in the persistent GERD symptoms suggests that the use of medications other than those that enhance gastric acid inhibitory effects would be an essential approach for the management of PPI-refractory GERD.

Randomised trial of acid inhibition by vonoprazan 10/20 mg once daily vs rabeprazole 10/20 mg twice daily in healthy Japanese volunteers (SAMURAI pH study).

Vonoprazan (V), a potassium-competitive acid blocker, has a more durable acid-inhibitory effect as compared with standard-dose proton pump inhibitors (PPIs) but has not been compared with 2-4 times higher daily PPI doses administered in two divided doses. To evaluate the acid-inhibitory effect of V 10/20mg once-daily (OD; V10/V20) vs rabeprazole (R) 10/20mg twice-daily (BID; R20/R40) in healthy Japanese volunteers. This multicentre, randomised, open-label, two-period, crossover study compared V10 or V20 vs R20, or V20 vs R40 using three cohorts of 10 healthy Japanese adults. Within each cohort, subjects were randomised to receive V or R for 7days and, following a washout period≥7days, the other treatment for 7days. On day 6 of each period, 24-hours multichannel gastric impedance-pH monitoring was performed. Percent times pH≥3, ≥4 and≥5 (pH 3, 4 and 5 holding time ratios [HTRs]) in 24hours were evaluated as primary pharmacodynamic endpoints. Acid-inhibitory effect (24-hours pH 3 HTR) of V20 was greater than those of R20 (91.0% vs 65.3%; P=.0049) and R40 (98.5% vs 85.9%; P=.0073). Similar results were obtained for 24-hours pH 4 and 5 HTRs. V20 also achieved greater nocturnal pH 4 (91.5% vs 73.2%; P=.0319) and 5 HTRs (78.8% vs 62.2%; P=.0325) as compared with R40. One subject (20%) developed diarrhoea while receiving R40 which was considered treatment-related. Compared with 2-4 times the standard daily dose of R, V20 exerts a more potent and durable acid-inhibitory effect. Trial identifier: UMIN000022198 (www.umin.ac.jp/ctr/index.htm).