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Alimentary Pharmacology & Therapeutics Jul 2023Treatment of acid-related disorders relies on gastric acid suppression. The percentage of time intragastric pH is >4 (pH >4 holding time ratio [HTR]) is important for...
BACKGROUND
Treatment of acid-related disorders relies on gastric acid suppression. The percentage of time intragastric pH is >4 (pH >4 holding time ratio [HTR]) is important for healing erosive oesophagitis; and the pH >6 HTR is critical for eradication of Helicobacter pylori infection, as bacterial replication is active and antibiotic effectiveness is optimised. Vonoprazan, a potassium-competitive acid blocker approved in the USA and other countries, suppresses gastric acid secretion in a predictable, rapid and consistent manner, extended over prolonged periods.
AIM
To explore the relationship between vonoprazan exposure and pH HTR through a pharmacokinetic/pharmacodynamic (PK/PD) model.
METHODS
We pooled data from Phase 1 studies with intragastric pH measurements. Pharmacokinetic profiles were predicted for study participants using an existing population pharmacokinetic model. Pharmacokinetic and pharmacodynamic data were merged, and three direct-link PK/PD models were derived and used to simulate pH HTRs with between-participant variability for pH >4, >5 and >6, for vonoprazan doses of 20 mg once and twice daily.
RESULTS
We used data from five Phase 1 studies to derive the PK/PD model. These included 245 participants (95.1% male, 50.6% Japanese and 49.4% non-Asian). Pre-dose, the mean pH >4 HTR was 6.4%, pH >5 3.2% and pH >6 1.2%. After 7 days of dosing, simulations predicted pH >4 HTRs of 89.7% and 98.1%, and pH >6 HTRs of 53.1% and 75.3%, for vonoprazan 20 mg once and twice daily, respectively.
CONCLUSIONS
Vonoprazan 20 mg once- and twice-daily dosing demonstrated high, dose-dependent, 24-hour intragastric acid control in this PK/PD model, supporting clinical efficacy data in patients with acid-related disorders.
Topics: Humans; Male; Female; Helicobacter Infections; Proton Pump Inhibitors; Helicobacter pylori; Peptic Ulcer; Pyrroles; Esophagitis
PubMed: 37066678
DOI: 10.1111/apt.17510 -
Journal of Pediatric Gastroenterology... Mar 2024Gastroesophageal reflux disease (GERD) is frequent and prolonged in esophageal atresia (EA) pediatric patients requiring routine use of proton pump inhibitors (PPIs).... (Meta-Analysis)
Meta-Analysis Review
Gastroesophageal reflux disease (GERD) is frequent and prolonged in esophageal atresia (EA) pediatric patients requiring routine use of proton pump inhibitors (PPIs). However, there are still controversies on the prophylactic use of PPIs and the efficacy of PPIs on GERD and EA complications in this special condition. The aim of the study is to assess the prophylactic use of PPIs in pediatric patients with EA and its complications. We, therefore, performed a systematic review including all reports on the subject from 1980 to 2022. We conducted meta-analysis of the pooled proportion of PPI-and no PPI groups using random effect model, meta-regression, and estimate heterogeneity by heterogeneity index I . Thirty-eight reports on the topic met the criteria selection, representing a cumulative 6044 patients with EA. Prophylactic PPI prescription during the first year of life does not appear to prevent GERD persistence at follow-up and is not associated with a significantly reduced rate of antireflux surgical procedures (ARP). PPIs improve peptic esophagitis and induce remission of eosinophilic esophagitis at a rate of 50%. Their effect on other GERD outcomes is uncertain. Evidence suggests that PPIs do not prevent anastomotic stricture, Barrett's esophagus, or respiratory complications. PPI use in EA can improve peptic and eosinophilic esophagitis but is ineffective on the other EA complications. Side effects of PPIs in EA are almost unknown.
Topics: Humans; Child; Proton Pump Inhibitors; Esophageal Atresia; Eosinophilic Esophagitis; Gastroesophageal Reflux; Esophagitis, Peptic
PubMed: 38262739
DOI: 10.1002/jpn3.12115 -
Alimentary Pharmacology & Therapeutics Mar 2024Laryngopharyngeal reflux has classically referred to gastroesophageal reflux leading to chronic laryngeal symptoms such as throat clearing, dysphonia, cough, globus... (Review)
Review
BACKGROUND
Laryngopharyngeal reflux has classically referred to gastroesophageal reflux leading to chronic laryngeal symptoms such as throat clearing, dysphonia, cough, globus sensation, sore throat or mucus in the throat. Current lack of clear diagnostic criteria significantly impairs practitioners' ability to identify and manage laryngopharyngeal reflux.
AIMS
To discuss current evidence-based diagnostic and management strategies in patients with laryngopharyngeal reflux.
METHODS
We selected studies primarily based on current guidelines for gastroesophageal reflux disease and laryngopharyngeal reflux, and through PubMed searches.
RESULTS
We assess the current diagnostic modalities that can be used to determine if laryngopharyngeal reflux is the cause of a patient's laryngeal symptoms, as well as review some of the common treatments that have been used for these patients. In addition, we note that the lack of a clear diagnostic gold-standard, as well as specific diagnostic criteria, significantly limit clinicians' ability to determine adequate therapies for these patients. Finally, we identify areas of future research that are needed to better manage these patients.
CONCLUSIONS
Patients with chronic laryngeal symptoms are complex due to the heterogenous nature of symptom pathology, inconsistent definitions and variable response to therapies. Further outcomes data are critically needed to help elucidate ideal diagnostic workup and therapeutic management for these challenging patients.
Topics: Humans; Laryngopharyngeal Reflux; Esophagitis, Peptic
PubMed: 38192086
DOI: 10.1111/apt.17858 -
The Korean Journal of Gastroenterology... Aug 2023The management decisions regarding gastroesophageal reflux disease (GERD) may differ according to the presence of erosive esophagitis. On the other hand, the...
BACKGROUND/AIMS
The management decisions regarding gastroesophageal reflux disease (GERD) may differ according to the presence of erosive esophagitis. On the other hand, the availability of upper endoscopy in Indonesia is relatively limited. This study compared the Reflux Disease Questionnaire (RDQ) and the GERD questionnaire (GERDQ) performance in predicting the presence of clinically significant erosive esophagitis and determined the validity and reliability of the Indonesian-translated version of RDQ.
METHODS
Ninety-two adults with GERD suspicion were recruited. All patients completed RDQ and GERDQ. Receiver operating curve analysis was conducted on RDQ and GERDQ to evaluate their performance in discriminating LA GERD B or higher esophagitis from others. The translated RDQ preserved its main structure and was culturally adapted.
RESULTS
The patients were 66.3% female and 73.9% Javanese. Only 22 (23.9%) patients presented with LA grade B or higher erosive esophagitis. The RDQ showed a higher AUC than the GERDQ (0.602 vs. 0.589). A cutoff point of 20 was selected for the RDQ with sensitivity and specificity of 73% and 50%, respectively, whereas the optimal cutoff point of GERDQ was 8, with a sensitivity and specificity of 77% and 43%, respectively. The r-value greater than the critical value table (r>0.205, p<0.01) confirmed the construct validity of our translated RDQ. The questionnaire also demonstrated excellent reliability (α=0.900) and moderate similarity with the Indonesian version of GERDQ (κ=0.459, p<0.01).
CONCLUSIONS
The RDQ is slightly superior to GERDQ in predicting the presence of clinically significant erosive esophagitis (LA grade B or higher). The Indonesian-translated RDQ is valid and reliable.
Topics: Adult; Humans; Female; Male; Reproducibility of Results; Esophagitis; Gastroesophageal Reflux; Peptic Ulcer
PubMed: 37621243
DOI: 10.4166/kjg.2023.027 -
Acta Cirurgica Brasileira 2024Reflux esophagitis is a condition characterized by inflammation and irritation of the esophagus, resulting from the backflow of stomach acid and other gastric contents...
PURPOSE
Reflux esophagitis is a condition characterized by inflammation and irritation of the esophagus, resulting from the backflow of stomach acid and other gastric contents into the esophagus. Columbianadin is a coumarin derivative that exhibits anti-inflammatory and antioxidant effects. In this study, we tried to scrutinize the protective effect of Columbianadin against acute reflux esophagitis in rats.
METHODS
RAW 264.7 cells were utilized to assess cell viability and measure the production of inflammatory parameters. The rats received anesthesia, and reflux esophagitis was induced via ligation of pylorus and fore stomach and corpus junction. Rats received the oral administration of Columbianadin (25, 50 and 100 mg/kg) and omeprazole (20 mg/kg). The gastric secretion volume, acidity, and pH were measured. Additionally, the levels of oxidative stress parameters, cytokines, and inflammatory markers were determined. At the end of the study, mRNA expression was assessed.
RESULTS
Columbianadin remarkably suppressed the cell viability and production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and prostaglandin (PGE2). Columbianadin treatment remarkably suppressed the secretion of gastric volume, total acidity and enhanced the pH level in the stomach. Columbianadin remarkably altered the level of hydrogen peroxidase, free iron, calcium, and plasma scavenging activity, sulfhydryl group; oxidative stress parameters like malonaldehyde, glutathione, superoxide dismutase, catalase, glutathione peroxidase; inflammatory cytokines viz., TNF-α, IL-6, IL-1β, IL-10, IL-17, and monocyte chemoattractant protein-1; inflammatory parameters including PGE2, iNOS, COX-2, and nuclear kappa B factor (NF-κB). Columbianadin remarkably (P < 0.001) suppressed the mRNA expression TNF-α, IL-6, IL-1β and plasminogen activator inhibitor-1.
CONCLUSIONS
Columbianadin demonstrated a protective effect against acute reflux esophagitis via NF-κB pathway.
Topics: Animals; Esophagitis, Peptic; NF-kappa B; Male; Rats; Oxidative Stress; Cytokines; Disease Models, Animal; Cell Survival; Acute Disease; RAW 264.7 Cells; Mice; Rats, Wistar; Signal Transduction; Antioxidants; Anti-Inflammatory Agents
PubMed: 38716957
DOI: 10.1590/acb391824 -
Journal of Gastroenterology and... Apr 2024Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND AND AIM
Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE).
METHODS
This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group.
RESULTS
A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm.
CONCLUSION
This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.
Topics: Humans; Amines; Double-Blind Method; Esomeprazole; Esophagitis, Peptic; Gastroesophageal Reflux; Peptic Ulcer; Proton Pump Inhibitors; Pyrroles; Treatment Outcome
PubMed: 38251791
DOI: 10.1111/jgh.16471 -
Journal of Gastroenterology Mar 2024Patients with systemic sclerosis (SSc) often have esophageal motility abnormalities and weak esophago-gastric junction (EGJ) barrier function, which causes proton pump...
BACKGROUNDS
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
Topics: Humans; Esophagitis, Peptic; Japan; Prevalence; Retrospective Studies; Risk Factors; Scleroderma, Systemic; Proton Pump Inhibitors; Manometry; Pyrroles; Sulfonamides
PubMed: 38252140
DOI: 10.1007/s00535-024-02076-0 -
Medicine Sep 2023Proton pump inhibitors (PPIs) are among the most prescribed and widely used medications; however, the long-term effects of these medications are only beginning to be... (Review)
Review
Proton pump inhibitors (PPIs) are among the most prescribed and widely used medications; however, the long-term effects of these medications are only beginning to be investigated. Since the introduction of omeprazole in 1989, PPIs have become the first-choice treatment for esophagitis, peptic ulcer disease, Zoster-Ellison syndrome, dyspepsia, and the prevention of ulcers with non-steroidal anti-inflammatory drugs. Recent studies have specifically examined the rise in celiac disease (CD) in this context. This review explores how PPIs may impact the development of CD and highlights the need for additional research into the environmental and genetic factors that influence the development and progression of the disease. A literature search was performed using the keywords celiac disease, proton pump inhibitors, human leukocyte antigen (HLA)-DQ2, HLA-DQ8. The pathogenesis of CD is multifactorial, and human leukocyte antigens are one factor that may contribute to its development. Additionally, pharmaceuticals, such as PPIs, that cause gut dysbiosis have been linked to the inflammatory response present in CD. Recent studies have suggested that the rise in CD could be attributed to changes in the gut microbiome, highlighting the significant role that gut microbiota is proposed to play in CD pathogenesis. Although PPI therapy is helpful in reducing acid production in gastroesophageal disorders, additional information is needed to determine whether PPIs are still an appropriate treatment option with the possibility of developing CD in the future, particularly in the context of HLA-DQ2 and HLA-DQ8 predispositions. This review emphasizes the importance of personalized medicine for individuals with gastroesophageal disorders that require long-term use of PPIs.
Topics: Humans; Proton Pump Inhibitors; Genetic Predisposition to Disease; Celiac Disease; Omeprazole
PubMed: 37746961
DOI: 10.1097/MD.0000000000035351 -
Journal of Pediatric Gastroenterology... Jun 2024Esophageal food impaction (EFI) is the sudden onset of dysphagia that occurs when a food bolus becomes lodged in the esophagus, requiring endoscopic removal. Scientific...
OBJECTIVES
Esophageal food impaction (EFI) is the sudden onset of dysphagia that occurs when a food bolus becomes lodged in the esophagus, requiring endoscopic removal. Scientific data on the prevalence and causes of EFI in children is lacking. The aim of this study was to provide further insights into EFI episodes in children.
METHODS
We have prospectively enrolled all children admitted for a first episode of EFI between March 2018 and March 2023. A fluoroscopic contrast study was performed in all patients to confirm the boluses and assess their position. Boluses were extracted by esophagogastroduodenoscopies, and esophageal biopsies were routinely obtained for histologic evaluation.
RESULTS
Over the study period, 41 children were admitted for a first episode of food impaction. Drooling was the most commonly reported symptom. Half children experiencing a first episode of food bolus were diagnosed with EoE (20/41, 48.8%). Almost a fourth of the episodes subtended a different condition, such as esophageal anastomotic, peptic or congenital strictures, stricturing caustic esophagitis, esophageal duplication, and achalasia. In the last fourth of patients the cause of EFI was not identified and thus probably related to quick eating and inadequate chewing of food.
DISCUSSION
Our study represents the largest known series of pediatric patients evaluated for food bolus impaction. Our main finding is the high frequency of EoE, which accounts for a half of EFI episodes in pediatric age, especially in older children. This finding highlights the importance of obtaining esophageal biopsies after the endoscopic bolus removal in children with EFI to provide a complete diagnostic evaluation.
Topics: Humans; Female; Male; Child, Preschool; Child; Prospective Studies; Deglutition Disorders; Esophagus; Food; Infant; Foreign Bodies; Endoscopy, Digestive System; Adolescent; Fluoroscopy
PubMed: 38623937
DOI: 10.1002/jpn3.12222 -
Journal of Oral Rehabilitation Feb 2024The prevalence between erosive tooth wear (ETW) in association with reflux oesophagitis (RO) has been reported. However, the severity of both diseases and the...
Patients with gastroesophageal reflux disease (both reflux oesophagitis and non-erosive reflux disease): Prevalence and severity of erosive tooth wear and saliva properties.
BACKGROUND
The prevalence between erosive tooth wear (ETW) in association with reflux oesophagitis (RO) has been reported. However, the severity of both diseases and the relationship between ETW and non-erosive reflux disease (NERD) is unclear.
OBJECTIVES
The prevalence and severity of ETW were investigated in RO, NERD and healthy controls.
METHODS
135 patients with RO, 65 with NERD and 40 healthy controls were recruited for this case-control study. A modified tooth wear index was used to evaluate the prevalence and severity of ETW. Salivary secretion and buffer capacity were assessed prior to endoscopy. The prevalence and severity of ETW, saliva properties among each group were analysed using Pearson's chi-squared test.
RESULTS
A total of 135 cases (56.3%) were categorised as the patient with ETW (55 with mild RO, 49 with severe RO and 31 with NERD). There was a significant relationship between the prevalence of RO and ETW, while there was no significant correlation between the prevalence of NERD and ETW. There was a significant difference related to the severity between RO and ETW. For salivary secretion, there was a significant difference between with and without ETW in patients with mild RO, severe RO and NERD. There was a significant difference between with and without ETW for salivary buffer capacity in patients with mild and severe RO.
CONCLUSION
There was a significant association of the prevalence and severity between RO and ETW. Clinical signs such as ETW and salivary buffer capacity depended on the severity of RO.
Topics: Humans; Esophagitis, Peptic; Non-Erosive Reflux Disease; Saliva; Prevalence; Case-Control Studies; Gastroesophageal Reflux; Tooth Wear; Tooth Erosion
PubMed: 37727994
DOI: 10.1111/joor.13595