Proton Pump Research Articles

S958 Proton Pump Inhibitor Infusion Misuse and Associated Risk Factors in a Community Hospital Setting

S958 Proton Pump Inhibitor Infusion Misuse and Associated Risk Factors in a Community Hospital Setting

Impact of Surgical Technique on Gastroesophageal Reflux Disease After Laparoscopic Sleeve Gastrectomy: A Nationwide Observational Study

BackgroundLaparoscopic sleeve gastrectomy (LSG) has gained increasing popularity worldwide, yet concerns persist regarding the development of gastroesophageal reflux disease (GERD) postoperatively. ObjectiveThis study aimed to evaluate the influence of technical aspects of LSG, specifically bougie size and distance from the pylorus to resection line edge, on the risk of developing symptomatic GERD within two years following surgery. SettingData from the Scandinavian Obesity Surgery Registry and the National Prescribed Drug Register were utilized for this analysis. MethodA retrospective observational study was conducted encompassing all LSG patients in Sweden between 2012 and 2020 who did not receive preoperative proton pump inhibitor (PPI) prescriptions. Patients were categorized based on bougie size and pyloric distance. Regular PPI use, defined as a dispensed prescription of more than 300 tablets per year, was employed as a proxy measure of symptomatic GERD and was compared between the groups. ResultsThe study included 7435 patients with complete data on dispensed PPI prescription both preoperatively and throughout the two-year follow-up period. Information on Bougie size and pyloric distance was available for 97.4% and 84.9%, respectively. Narrower bougie size and greater pyloric distance were associated with increased risk of regular PPI use post-surgery. Advanced age and female sex were independent risk factors for post-LSG regular PPI use, while initial BMI, total weight loss, and comorbidities showed no significant associations. ConclusionUsing a narrow bougie and initiating resection at a greater distance from the pylorus were associated with higher risk of symptomatic de novo GERD following LSG.

Challenges in Diagnosing Pantoprazole-Induced Drug Fever: A Case Report in a Critically Ill Patient

Drug fever remains a diagnostic challenge in clinical practice. Proton pump inhibitors (PPIs), like pantoprazole, are rarely implicated in drug fever cases despite their widespread use. We present a case of a 56-year-old man hospitalized for acute hematemesis, who developed persistent fever despite antimicrobial therapy. Fever resolved rapidly upon discontinuing pantoprazole, confirming pantoprazole-induced drug fever. This case highlights the diagnostic complexities of drug fever in critically ill patients and underscores the importance of considering less commonly suspected agents like pantoprazole to avoid unnecessary treatments and prolonged hospitalizations.

Efficacy and Safety of Potassium-competitive Acid Blockers Versus Proton Pump Inhibitors in Treating Erosive Esophagitis: A Meta-analysis Based on Randomized Controlled Trials.

This meta-analysis aimed to investigate the efficacy and safety of potassium-competitive acid blockers (P-CABs) and proton pump inhibitors (PPIs) in treating erosive esophagitis (EE). PubMed, Embase, Cochrane Library, and Web of Science were systematically searched using predefined search terms up to January 2024. Relevant randomized controlled trials were included. The outcoming were the EE healing rate and treatment-related adverse events incidence. Nine randomized controlled trials involving 4012 patients were included. Patients receiving P-CAB exhibited a significantly better overall healing rate compared with PPI at week 2 [risk ratio (RR) = 1.06], but no statistical difference was observed at week 4 and week 8. Subgroup analysis revealed that P-CAB demonstrated a higher healing rate for patients with Los Angeles (LA) grade C/D, regardless of the assessment at week 2 (RR = 1.17), week 4 (RR = 1.10), or week 8 (RR = 1.08). However, no significant difference was found between PPI and P-CAB for patients with LA grade A/B at week 2, week 4, or week 8. Furthermore, patients treated with P-CAB had lower recurrence rates during maintenance therapy compared with PPI (RR = 0.79). In terms of safety, P-CAB was associated with a lower incidence of headache compared with PPI (RR = 0.32), with no statistical difference found in any treatment-related adverse events between the two groups. P-CAB was found to be safe and effective for EE treatment compared with PPI, particularly in 2-week short-term treatment, severe EE (LA grade C/D) treatment, or maintenance therapy. Limitations such as potential heterogeneity among included trials should be considered in the interpretation of these findings.

Nonvitamin K Anticoagulants: Risk of Bleeding When Interacting With Other Medications: A Cohort Study From Medicare.

Patients on nonvitamin K antagonist (NVKA) are usually taking other drugs. Potential interaction may increase the gastrointestinal (GI) bleeding risk associated with NVKA. Observational cohort study using Medicare data from 2017 to 2020. Participants receiving a NVKA were included. A concomitant overlapping period while on NVKA was assessed for nonsteroidal anti-inflammatory drugs (NSAIDS), selective serotonin reuptake inhibitors (SSRI), antiplatelets, glucocorticoids, aspirin and proton pump inhibitors (PPI). A logistic regression predicting either any bleeding or GI bleeding was conducted estimating the odds ratio (OR) and 95% confidence interval (CI). A total of 102 531 people on NVKA with mean age 77 years (SD = 9.8) and 55% females (N = 56 671) were included. Previous history of GI bleeding occurred in 2 908 (2.8%) participants, concomitant exposure to PPI occurred in 38 713 (38%), SSRI in 16 487 (16%), clopidogrel in 15 795 (15.4%), NSAIDs in 13 715 (13.4%) and glucocorticoids in 13 715 (13.4%). Risk for any bleeding was shown for clopidogrel (OR: 1.37, 95% CI: 1.30, 1.44), prasugrel/ticagrelor (OR: 1.36, 95% CI: 1.18, 1.58), glucocorticoids (OR: 1.26, 95% CI: 1.19, 1.34), and SSRIs (OR: 1.13, 95% CI: 1.07, 1.19). GI bleeding risk was shown for clopidogrel (OR: 1.44, 95% CI: 1.34, 1.55), prasugrel/ticagrelor (OR: 1.47, 95% CI: 1.20, 1.79), SSRIs (OR: 1.09, 95% CI: 1.01, 1.17) and glucocorticoids (OR: 1.33, 95% CI: 1.23, 1.44). PPI use was correlated with both NSAID (r = 0.07, p ≤ 0.0001) and SSRI use (r = 0.09, p ≤ 0.0001). NVKA concomitantly taken with antiplatelets, glucocorticoids, and SSRIs showed an increased risk for any bleeding and GI bleeding.

S592 Association of Osteoporosis and Hip Fractures in Patients Who Use Proton Pump Inhibitors: A Multicenter Propensity Score Matching Analysis

S592 Association of Osteoporosis and Hip Fractures in Patients Who Use Proton Pump Inhibitors: A Multicenter Propensity Score Matching Analysis

Association between exposure to proton pump inhibitors and delirium: a descriptive and disproportionality analysis of VigiBase

ObjectivesProton pump inhibitor (PPI) exposure can lead to hyponatraemia, which is a common cause of delirium. An association between PPI exposure and delirium without hyponatraemia has been suggested in the...

S2093 Exploring Proton Pump Inhibitor Optimization of Post-RYGB Marginal Ulceration Recurrence

S2093 Exploring Proton Pump Inhibitor Optimization of Post-RYGB Marginal Ulceration Recurrence

S660 Reducing Inappropriate Use of Proton Pump Inhibitors in Outpatient Settings: A Quality Improvement Project

S660 Reducing Inappropriate Use of Proton Pump Inhibitors in Outpatient Settings: A Quality Improvement Project

TCT-7 Impact of Use of Proton Pump Inhibitor in Patients Taking Clopidogrel: A Meta-Analysis of Randomized Controlled Trials

TCT-7 Impact of Use of Proton Pump Inhibitor in Patients Taking Clopidogrel: A Meta-Analysis of Randomized Controlled Trials

Enantioselective Binding of Proton Pump Inhibitors to Alpha1-Acid Glycoprotein and Human Serum Albumin-A Chromatographic, Spectroscopic, and In Silico Study.

The enantioselective binding of three proton pump inhibitors (PPIs)-omeprazole, rabeprazole, and lansoprazole-to two key plasma proteins, α1-acid glycoprotein (AGP) and human serum albumin (HSA), was characterized. The interactions between PPI enantiomers and proteins were investigated using a multifaceted analytical approach, including high-performance liquid chromatography (HPLC), fluorescence and UV spectroscopy, as well as in silico molecular docking. HPLC analysis demonstrated that all three PPIs exhibited enantioseparation on an AGP-based chiral stationary phase, suggesting stereoselective binding to AGP, while only lansoprazole showed enantioselective binding on the HSA-based column. Quantitatively, the S-enantiomers of omeprazole and rabeprazole showed higher binding affinity to AGP, while the R-enantiomer of lansoprazole displayed greater affinity for AGP, with a reversal in the elution order observed between the two protein-based columns. Protein binding percentages, calculated via HPLC, were greater than 88% for each enantiomer across both transport proteins, with all enantiomers displaying higher affinity for AGP compared to HSA. Thermodynamic analysis indicated that on the HSA, the more common, enthalpy-controlled enantioseparation was found, while in contrast, on the AGP, entropy-controlled enantioseparation was observed. The study also identified limitations in using fluorescence titration due to the high native fluorescence of the compounds, whereas UV titration was effective for both proteins. The determined logK values were in the range of 4.47-4.83 for AGP and 4.02-4.66 for HSA. Molecular docking supported the experimental findings by revealing the atomic interactions driving the binding process, with the predicted enantiomer elution orders aligning with experimental data. The comprehensive use of these analytical methods provides detailed insights into the enantioselective binding properties of PPIs, contributing to the understanding of their pharmacokinetic differences and aiding in the development of more effective therapeutic strategies.

Assessment of Awareness and Knowledge of Proton Pump Inhibitors Among the General Population in Lahore, Pakistan

Background Proton pump inhibitors (PPIs) are used for various conditions and are generally considered safe drugs; however, there has been a surge in their usage over time, partially related to their safety and overprescription. Purpose This study is aimed to assess how much the public of Lahore knows about PPI, and how they use it, and if they follow their physician’s instructions or not. Methods A cross-sectional study was planned to attain the objective of the study. Respondents visiting various community pharmacies were inquired about their willingness to participate in this study. Chi-square was used to find the association between sociodemographic parameters and awareness of PPIs. p value less than 0.05 was considered statistically significant. Results There were mostly university students (73.7%), with 82.2% having heard of PPIs. Prevalent use (86.85%) is observed, often after a medical condition. Notably, 60.1% use PPIs as needed, but only 52.3% complete the prescribed course. PPIs were taken before meals only by 69.3% of participants. Associations exist between having heard of PPIs, and age with younger participants ( p < 0.001) exhibiting less awareness. Females also have heard lesser of PPIs ( p = 0.011). Education correlates with unawareness ( p < 0.001), and many participants are unaware of PPI side effects (51.04%). Conclusion The study contributes valuable insights to the understanding of PPI usage perspectives, offering implications for healthcare practices and public health awareness campaigns. Overall, the public shows signs of awareness but those are not enough to eliminate the misuse of PPIs in Lahore.

Eosinophilic esophagitis (EoE) in adults in Icelandic and international context

Eosinophilic esophagitis (EoE) is a common cause of swallowing difficulties in both children and adults. The incidence of EoE has been increasing over the past decades, which cannot be solely attributed to improved diagnostic techniques. EoE is more common in adults than in children. The diagnosis is confirmed by a biopsy from the esophageal mucosa showing a significant infiltration of eosinophils. Many patients respond to treatment with proton pump inhibitors, but those with severe EoE may require dietary modifications, topical steroids, and/or dilation of esophageal strictures. This review covers the incidence, risk factors, natural course, diagnosis, and treatment options for EoE, both within the Icelandic healthcare system andi n a broader context.

S619 Clinicians Report Uncertainty Regarding Approaches to Treatment Beyond Proton Pump Inhibitors in Eosinophilic Esophagitis

S619 Clinicians Report Uncertainty Regarding Approaches to Treatment Beyond Proton Pump Inhibitors in Eosinophilic Esophagitis

The relationship between serum uric acid and gastrointestinal bleeding in peritoneal dialysis patients: a propensity score analysis

Purpose Gastrointestinal bleeding is an important gastrointestinal complication among peritoneal dialysis patients and correlated with a higher risk of mortality. Increased uric acid levels are a significant complication for peritoneal dialysis patients and have been associated with an increased risk of hemorrhagic stroke. The objective of the present study was to investigate the relationship between serum uric acid levels and gastrointestinal bleeding in peritoneal dialysis patients. Methods A total of 2498 peritoneal dialysis patients were recruited. Based on the optimal uric acid cutoff value, two groups of patients were divided. We constructed a propensity-score-matched population of 1762 patients by matching sex, age, and body mass index. Survival outcomes between the two groups were compared using adjusted Kaplan–Meier curves. We constructed the restricted cubic splines regression to assess the correlation between levels of uric acid and gastrointestinal bleeding. A multivariate Cox proportional hazards regression was performed to test whether higher levels of uric acid are an independent risk factor for gastrointestinal bleeding. We performed a forest plot to show interaction effects in different subgroups. Results According to restricted cubic splines regression, uric acid levels were positively correlated with the risk of gastrointestinal bleeding events. After adjusted different confounding factors, patients with high levels of uric acid were prone to experience gastrointestinal bleeding (HR 1.868, 95%CI 1.001–3.486). In subgroups, the interaction between higher levels of uric acid and utilizing proton pump inhibitors was significant (P for interaction = 0.034). Further research found that taking proton pump inhibitors could decrease the risk of gastrointestinal bleeding in peritoneal dialysis patients accompanied high levels of uric acid. Conclusion The baseline high levels of uric acid are an independent risk factor for gastrointestinal bleeding in patients undergoing peritoneal dialysis.

P2.11A.11 Impact of Proton Pump Inhibitor Use on Faecal Microbiome in Patients with NSCLC Treated with Immune Checkpoint Inhibitor

P2.11A.11 Impact of Proton Pump Inhibitor Use on Faecal Microbiome in Patients with NSCLC Treated with Immune Checkpoint Inhibitor

Anisotropic Superprotonic Conduction in a Layered Single-Component Hydrogen-Bonded Organic Framework with Multiple In-Plane Open Channels.

Hydrogen-bonded organic frameworks (HOFs) are promising proton conductive materials because of their inherent and abundant hydrogen-bonding sites. However, most superprotonic-conductive HOFs are constructed from multiple components to enable favorable framework architectures and structural integrity. In this contribution, layered HOF-TPB-A3 with a single component is synthesized and exfoliated. The exfoliated nanoplates exhibited anisotropic superprotonic conduction, with in-plane proton conductivities reaching 1.34×10-2 S cm-1 at 296 K and 98% relative humidity (RH). This outperforms the previously reported single-component HOFs and is comparable with the state-of-the-art multiple-component HOFs. The high and anisotropic proton conductive properties can be attributed to the efficient proton transport along multiple open channels parallel to their basal planes. Moreover, an all-solid-state (ASS) proton rectifier device is demonstrated by combining HOF-TPB-A3 and a hydroxide ion-conducting layered double hydroxide (LDH). This work suggests that single-component HOFs with multiple open channels offer more opportunities as versatile platforms for proton conductors, making them promising candidates for conducting media in protonic devices.

Cellular NS1-BP protein interacts with the mRNA export receptor NXF1 to mediate nuclear export of influenza virus M mRNAs

Influenza A viruses have eight genomic RNAs that are transcribed in the host cell nucleus. Two of the viral mRNAs undergo alternative splicing. The M1 mRNA encodes the matrix protein 1 (M1) and is also spliced into M2 mRNA, which encodes the proton channel matrix protein 2 (M2). Our previous studies have shown that the cellular NS1-binding protein (NS1-BP) interacts with the viral non-structural protein 1 (NS1) and M1 mRNA to promote M1 to M2 splicing. Another pool of NS1 protein binds the mRNA export receptor NXF1 (nuclear RNA export factor-1), leading to nuclear retention of cellular mRNAs. Here we show a series of biochemical and cell biological findings that suggest a model for nuclear export of M1 and M2 mRNAs despite the mRNA nuclear export inhibition imposed by the viral NS1 protein. NS1-BP competes with NS1 for NXF1 binding, allowing the recruitment of NXF1 to the M mRNAs after splicing. NXF1 then binds GANP (Germinal-center Associated Nuclear Protein), a member of the TRanscription and EXport complex (TREX)-2. Although both NS1 and NS1-BP remain in complex with GANP-NXF1, they dissociate once this complex docks at the nuclear pore complex (NPC), and the M mRNAs are translocated to the cytoplasm. Since this mRNA nuclear export pathway is key for expression of M1 and M2 proteins that function in viral intracellular trafficking and budding, these viral-host interactions are critical for influenza virus replication.

Comprehensive analysis of nizatidine: Pharmacodynamics and pharmacokinetics in anti-ulcer treatment

Ulcers are characterized histologically as lesions that penetrate through the muscularis mucosae into the submucosal layer, affecting any segment of the gastrointestinal (GI) tract mucosa. They often arise due to excessive acid production from peptic secretions. Nizatidine (NZT) is a potent H2-receptor antagonist used to reduce basal, nocturnal, and stimulated gastric acid secretion. This medication is commonly prescribed for conditions such as gastroesophageal reflux disease, peptic ulcers, and duodenal ulcers. As a member of the histamine H2 receptor antagonist class introduced before proton pump inhibitors, Nizatidine is noted for its effectiveness comparable to ranitidine. However, Nizatidine is distinguished by its thiazole ring, in contrast to the furan ring found in ranitidine. When administered orally, Nizatidine, especially in combination with antacids, enhances drug delivery to parietal cell receptors, improving the overall bioavailability of the medication and its ability to suppress acid secretion. Nizatidine is primarily absorbed in the proximal small intestine, exhibiting about 70% absolute bioavailability. Its lower absorption from the colon and a short biological half-life (ranging from 1 to 1.6 hours) suggest the potential benefits of developing sustained-release formulations such as floating gels to prolong its therapeutic effects. Clinical studies indicate that Nizatidine, in doses of 300 mg at bedtime or 150 mg twice daily, shows superior efficacy compared to other H2-receptor antagonists for managing duodenal and gastric ulcers as well as gastroesophageal reflux disease.

Cost-Effectiveness Analysis of Current Treatment Options for Eosinophilic Esophagitis.

The management strategies for eosinophilic esophagitis (EoE) include proton pump inhibitors (PPI), swallowed topical steroids (tCS), elimination diets, and the biologic agent dupilumab, although there remains little guidance on the selection of initial treament. We performed cost-effectiveness analyses to compare these approaches of first-line therapy. A Markov model was constructed from a payer perspective to evaluate the cost-effectiveness of first-line therapies for EoE, including PPI, tCS, and six-food elimination diet (SFED), with.crossover in treatments for primary and secondary non-response. The primary outcome was incremental cost-effectiveness ratio (ICER) at two- and five-year time horizons. Secondary analyses included modeling from a societal perspective that also accounted for patient-specific costs, as well as a separate simplified model comparing dupilumab to tCS and PPI. In the base-case scenario (five-year time horizon), the average costs were SFED:$15,296.81, PPI:$16,153.77, and tCS:$20,975.33 as initial therapy, with SFED being the dominant strategy (more effective/less costly), while PPI offered the lowest cost on a two-year time horizon. From a societal perspective, PPI was the dominant initial strategy on both two- and five-year time horizons. Amongst pharmacologic therapies, PPI was the most cost-effective first-line option. Dupilumab was not cost-effective relative to tCS, unless the quarterly cost is reduced from $7,311 to $2,038.50 per price threshold analysis under permissive modeling conditions. SFED was the most effective/least costly first-line therapy from payer perspective, while PPI was more cost-effective from societal perspective. PPI is also the most cost-effective pharmacologic strategy. Dupilumab requires substantial cost reductions to be considered cost-effective first-line pharmacotherapy.