Acid-suppressive Drugs Research Articles

Effects of trypsin and pepsin detection on chronic otitis media with effusion

Chronic otitis media with effusion (COME) is a common cause of hearing loss in children and adults. Laryngopharyngeal reflux (LPR) is often overlooked in the clinical management of COME complicated by LPR. This study aimed to investigate the presence and concentration of trypsin and pepsin in the middle ear effusion (MEE), as well as the recurrence rate of otitis media with effusion (OME) in COME patients with trypsin-/pepsin-positive MEE after acid-suppressive treatment (AST). In this study, trypsin and pepsin were found in the MEE of COME patients. Follow-up results showed that the recurrence rate of OME within 1 year was significantly lower in the AST group than in the non-AST group. Taken together, patients with COME can be offered pepsin detection of MEE, and if the pepsin test is positive, acid-suppressing drugs such as proton pump inhibitors could be recommended to prevent the recurrence of OME.

The role of P-CABs in GERD.

Potassium-competitive acid blockers (P-CABs) constitute a relatively new class of gastric acid-suppressing drugs. Among this class, vonoprazan is the first to have been approved in the United States. However, some P-CABs including vonoprazan, tegoprazan and fexuprazan have been available in other countries since at least 2014. The first aim of this article is to review pharmacological differences between P-CABs that are currently approved or in development with proton pump inhibitors (PPIs). The specific focus thereafter is on the likely role of P-CABs in the treatment of different manifestations of gastroesophageal reflux disease (GERD). Multiple clinical trials have compared P-CABs with PPIs in erosive esophagitis. Additional trials have compared P-CABs with placebo in non-erosive reflux disease. Relevant results are reviewed and inferences drawn for their use in the US. Lastly, consideration is given to additional, potential uses of P-CABs in the broader spectrum of GERD and some suggestions made for future research initiatives.

From theory to therapy: a One Health approach guides current and future acid suppressant use in veterinary medicine.

Acid-suppressant drugs (ASDs) have revolutionized the treatment of acid-related disorders such as gastroesophageal reflux and gastrointestinal ulceration in both human and veterinary species. However, continued advancement in this field is dependent on a shared understanding of both human and veterinary research as well as an appreciation for species similarities and differences. In this Currents in One Health article, we will compare the efficacy of and indications for ASDs in humans and small animals, noting species differences and knowledge gaps when applicable. We will also highlight areas where further research is needed, specifically emphasizing the need for more feline research and a better understanding of which diseases may benefit from gastroprotection. Finally, given the rising overuse of ASDs in both human and veterinary medicine, we will explore the known adverse effects of these drugs in dogs and cats. This article is focused on our current understanding of these drugs in veterinary medicine and their clinical implications. The companion Currents in One Health article by Gould et al, AJVR, October 2024, will explore the future of ASD research and use by evaluating these drugs' pH-independent effects in humans and rodent models.

PH-independent effects of acid suppressants in dogs and cats: a One Health perspective and case for further investigation.

Our understanding of the use of acid-suppressant drugs (ASDs) in companion animals is largely centered around the treatment of acid-related disorders including gastroesophageal reflux and gastrointestinal ulceration. The companion article by Grady et al, JAVMA, October 2024, summarizes our current knowledge of the efficacy of and indications for ASDs for the treatment of acid-related disorders. Far less is understood about both the benefits of and potential for adverse effects of ASDs outside of the parietal cell including those directed toward inflammation and immunomodulation, tumorigenesis, fibrosis, and oxidative stress. In this Currents in One Health article, we summarize the pH-independent properties of ASDs as demonstrated in studies conducted largely in humans and rodents. The objective of this review is to highlight and increase awareness of the pH-independent effects of ASDs to elucidate the need for further veterinary research in this area.

Retrospective evaluation of the effect of acid suppressant drugs on leukocyte ratios in dogs with mast cell tumors.

Acid suppressant drugs (ASDs) are commonly used to decrease gastric acid production, but some evidence exists that ASDs exert immunomodulatory effects. Such an effect has not been investigated in dogs for which ASDs are routinely prescribed. Compared to naïve subjects, dogs treated with ASDs will exhibit differences in leukocyte ratios after treatment. Fifty-one dogs with mast cell tumors (MCTs). Dogs with MCT that were either AS naïve or treated with ASDs (i.e., histamine-2-receptor antagonists [H2RA] or proton pump inhibitors [PPI]) were included in this retrospective study. Subjects were categorized into 3 treatment groups (AS naïve, H2RA treated, and PPI treated), and leukocyte ratios (neutrophil:eosinophil, lymphocyte:monocyte, and neutrophil:lymphocyte [NLR]) were calculated before and after treatment. A mixed effects analysis of variance on ranks was used to assess differences in ratios between treatments, between pre- and post-treatment time points, and between pre- and post-time points for each treatment. Concurrent administration of antihistamines, corticosteroids, and chemotherapeutic drugs was assessed as a confounding factor. Famotidine (n = 14/14) and omeprazole (n = 12/12) were the only H2RA and PPI used, respectively. Dogs receiving famotidine had a significant increase in median NLR from pre- to post-treatment (3.429; range, 1.417-15 to 5.631; range, 2.654-92; P < 0.01) compared to PPI treated or AS naïve dogs. No differences existed in chemotherapeutic drug or corticosteroid use between groups. A significant difference in NLR was identified in famotidine treated dogs compared with omeprazole treated or AS naïve dogs.

Comparative Efficacy and Safety of Potassium-Competitive Acid Blockers vs. Proton Pump Inhibitors for Peptic Ulcer with or without Helicobacter pylori Infection: A Systematic Review and Network Meta-Analysis.

Novel potassium-competitive acid blockers (P-CABs) have emerged as effective acid-suppressive drugs in recent years, replacing proton pump inhibitors (PPIs). We aim to compare the efficacy and safety of P-CABs versus PPIs in the treatment of peptic ulcers with or without Helicobacter pylori (H. pylori) infection. We searched in PubMed, Embase, WOS, Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang databases (all years up to January 2024). Efficacy and safety outcomes were evaluated using odds ratio (OR) and 95% confidence intervals (CI). The Surface Under the Cumulative Ranking (SUCRA) probabilities were used to rank each intervention. Among 14,056 studies screened, 56 studies involving 9792 participants were analyzed. Vonoprazan demonstrated the best efficacy in ulcer healing rate and H. pylori eradication rate (SUCRA = 86.4% and 90.7%, respectively). Keverprazan ranked second in ulcer healing rates (SUCRA = 76.0%) and was more effective in pain remission rates (SUCRA = 91.7%). The risk of adverse events was low for keverprazan (SUCRA = 11.8%) and tegoprazan (SUCRA = 12.9%), and moderate risk for vonoprazan (SUCRA = 44.3%) was demonstrated. Compared to lansoprazole, vonoprazan exhibited a higher risk of drug-related adverse events (OR: 2.15; 95% CI: 1.60-2.89) and serious adverse events (OR: 2.22; 95% CI: 1.11-4.42). Subgroup analysis on patients with H. pylori-positive peptic ulcers showed that vonoprazan was at the top of the SUCRA rankings, followed by keverprazan. Vonoprazan showed superior performance in peptic ulcers, especially for patients with H. pylori-positive peptic ulcers. However, the risk of adverse events associated with vonoprazan should be noted. Keverprazan has also shown good therapeutic outcomes and has performed better in terms of safety.

Efficacy of Tegoprazan in Patients With Functional Dyspepsia: A Prospective, Multicenter, Single-arm Study.

Acid-suppressive drugs, such as proton pump inhibitors (PPIs), are treatment options for functional dyspepsia (FD). However, the efficacy of potassium-competitive acid blockers (P-CABs) in treating FD has not yet been established. This prospective multicenter clinical trial-based study aimed to assess the efficacy and safety of tegoprazan as a P-CAB treatment in patients with FD. FD was diagnosed using the Rome IV criteria. All patients received tegoprazan 50 mg once daily for 8 weeks. Dyspeptic symptoms were assessed using a dyspepsia symptom questionnaire (5-point Likert scale, Nepean Dyspepsia Index-Korean [NDI-K], and gastroesophageal reflux disease-health-related quality of life [GERD-HRQL]). The main outcome was satisfactory symptom relief rates at 8 weeks. In this study, from the initial screening of 209 patients, 173 were included in the per-protocol set analysis. Satisfactory symptom relief rates at 8 and 4 weeks were 86.7% and 74.6%, respectively. In addition, the NDI-K and GERD-HRQL scores significantly improved at 8 and 4 weeks compared with the baseline scores. The efficacy of tegoprazan was not influenced by the FD subtype or Helicobacter pylori status. In patients with overlapping FD and GERD, there was a greater improvement in the NDI-K and GERD-HRQL scores than in patients with FD symptoms only. No serious drug-related adverse events occurred during this study. Tegoprazan (50 mg) administered once daily provided satisfactory symptom relief for FD.

Significant improvement of physicians' knowledge and clinical practice: an opportune, effective, and convenient continuing medical education program on functional dyspepsia.

This cohort study aimed to explore the effect of a one-day online continuing medical education (CME) on the improvement of physicians' knowledge and clinical practice on functional dyspepsia (FD). Physicians were invited to participate in this CME via medical education applications. FD training videos made in advance were sent to participants via a weblink. Before and after training, participants were required to finish the FD knowledge test and provide case information of FD patients. McNemar test, Wilcoxon rank-sum test, Freidman test, Chi-square test, quantile regression, and generalized estimating equations (GEE) were used to perform statistical analysis. There were 397 of 430 (92.33%) physicians finished this CME program. The total score of the FD knowledge test after training was significantly higher compared with before training [488.3 (468.3-510.0) vs. 391.7 (341.7-450.0), p < 0.001]. Particularly, physicians from primary hospitals show more increase in total scores than physicians from secondary and tertiary hospitals. According to the GEE model, receiving this online training was an independent predictor of physicians' choice of upper gastrointestinal endoscopy in patients with FD [OR 1.73, 95%CI (1.09-2.73), p = 0.020], especially in PDS. Also, it was an independent predictor of physicians' choice of acid-suppressive drugs in patients with FD [OR 1.30, 95%CI (1.03-1.63), p = 0.026], especially in EPS and PDS overlapping EPS. This one-day online CME program effectively and conveniently improved physicians' knowledge and clinical practice, providing new ideas for future CME and facilitating precise clinical management of FD patients with different subtypes especially in primary hospitals.

Responses of Proton Pump Inhibitors and Potassium-Competitive Acid Blockers According to Outcomes of Symptom, Endoscopy, and Histology in Patients With Eosinophilic Esophagitis.

We aimed to examine the response rate to proton pump inhibitors (PPIs) and potassium-competitive acid blockers and the prevalence of topical corticosteroid (TCS) therapy as the second-line treatment for eosinophilic esophagitis (EoE). Acid-suppressive drugs such as PPIs and potassium-competitive acid blockers are often used to treat EoE. Treatment response is based on outcomes including symptoms, endoscopy, and histology; however, the detailed response rate to PPI/P-CAB is unknown. In total, 236 patients with histologically confirmed EoE who received PPI/P-CAB as the first-line treatment were included. We assessed the symptoms, endoscopic reference score (EREFS), and histology [eosinophils per high-power field (eos/hpf)] 8 weeks after PPI/P-CAB administration. Complete normalization was defined as the disappearance of symptoms, EREFS score 0, or 0-1 eos/hpf, and response as disappearance or improvement of symptoms, EREFS score ≤2, or <15 eos/hpf. The prevalence of TCS therapy in each response group was assessed. Complete normalization was achieved in 25%, 50%, 36%, and 8% of patients for symptoms, endoscopy, histology, and all 3 outcomes, respectively. The response rates were 81%, 87%, 87%, 75%, and 60% for symptoms, endoscopy, histology, and all 3 outcomes, respectively. TCS use was significantly lower (8%) in patients who achieved response of all 3 outcomes than in other groups and was dependent on the number of outcomes with nonresponse. Complete normalization of symptoms, endoscopy, and histology using PPI/P-CAB is uncommon. Based on treatment efficacy by response/nonresponse, TCS was the secondary treatment in cases with an increase in the number of nonresponse outcomes.

Appropriateness and Cost of Prophylaxis Stress Ulcer for Inpatient in the Internal Medicine Department in a Government Hospital: A Cross-Sectional Study

Guidelines from the American Society of Health-System Pharmacists (ASHP) 1999 prohibit acid-suppressing therapy for stress ulcer prophylaxis (SUP) in patients who are not critically ill. Stress ulcer prophylaxis is not recommended in non-ICU patients with &lt;2 risk factors. Inappropriate use of SUP can increase costs for patients. This study aims to evaluate the use and the cost of SUP. This research was a non-experimental observational study with a cross-sectional approach. Data was collected retrospectively using the consecutive sampling method with a random sampling technique on the medical records of inpatients in the internal medicine ward of Sleman Regional Public Hospital from January to December 2020, totaling 340 samples. The results showed that proton pump inhibitors were the most widely used acid-suppressing drugs, with 45.8%. Furthermore, the histamine-2 receptor antagonist was 42.6%, the sucralfate group was 7.4%, and the antacid group was 4.2%. Of 340 patients, 57 (16.8%) were in the proper indication based on the guidelines, and 283 (83.2%) were under the wrong indication for SUP. They were using SUP with the proper indication so that the therapy could save treatment costs by Rp. 19,933,582. There was a high prevalence of inappropriate SUP prescriptions among inpatients in the internal medicine department; if these drugs were given with the appropriate indications, they could save more on the prophylaxis cost. Clinician pharmacists should develop an effective intervention strategy to reduce inappropriate SUP drugs.

Clinical factors associated with stable treatment of chronic constipation in Japanese patients

Background/AimsChronic constipation (CC) is one of the most common gastrointestinal disorders in the general population. Although there are many treatment options, achieving a stable treatment for CC remains one of the challenges in clinical practice. This study aimed to evaluate the clinical factors associated with stable treatment for CC in Japanese patients.MethodsA retrospective, cross-sectional, and multicenter study was carried out. Patients were eligible for inclusion if they fulfilled the Rome IV criteria for diagnosing CC and had been treated for at least one and a half years. Patients with up to two prescription modifications for CC in one year were defined as the stable treatment group, whereas those with three or more prescription changes were defined as the unstable treatment group. Univariate and multivariate analyses were carried out to identify factors associated with CC.ResultsA total of 114 patients have been recruited. There were 82 patients (77.0%) in the stable treatment group and 32 patients (23.0%) in the unstable treatment group. Based on multivariate likelihood analysis, only using acid-suppressive drugs contributed to stability treatment in CC patients (odds ratio: 2.81, 95% confidence interval: 1.12–7.08, p = 0.03).ConclusionAdministration of acid-suppressive drugs was the only factor related to the stability of CC treatment. Further studies are needed to validate the results as well as clarify the causes.

Changes in estimated glomerular filtration rate in patients administered proton pump inhibitors: a single-center cohort study.

Proton pump inhibitor (PPI) use may be associated with renal dysfunction. Renal dysfunction in PPI users requires evaluation of development and progression risks simultaneously, using estimated glomerular filtration rate (eGFR) slope, which indicates changes in eGFR per year. To the best of our knowledge, no studies have evaluated eGFR slope in PPI users. This study investigated the association between PPI use and renal dysfunction using eGFR slope.A single-center cohort study was conducted using the health records data at Hamamatsu University Hospital in Japan. Participants were defined as first users of acid-suppressing drugs (PPIs or Histamine H2 receptor antagonists (H2RAs)) from 2010 to 2021 and continuously prescribed for ≥ 90days. The H2RA group was used for the propensity-score matching (PSM) to the PPI group to minimize the effects of confounders. The eGFR slope was estimated using a linear mixed effects model. Participants were stratified by baseline eGFR and age, respectively, as subgroup analyses.A total of 4,649 acid-suppressing drug users met the inclusion criteria, including 950 taking H2RAs and 3,699 PPIs. After PSM, 911 patients were assigned to each group. The eGFR slopes of the PPI and H2RA users were -4.75 (95% CI: -6.29, -3.20) and -3.40 (-4.38, -2.42), respectively. The difference between the groups was not significant. Significant declines in eGFR were observed with PPIs with baseline eGFR ≥ 90 and age < 65.PPI use for ≥ 90days may hasten eGFR decline compared to H2RA use, especially in patients with eGFR ≥ 90 or age < 65.

Acid-suppressive drugs: A systematic review and network meta-analysis of their nocturnal acid-inhibitory effect.

Acid-suppressive drugs (ASDs) are widely used in many gastric acid-associated diseases. Nocturnal acid breakthrough has been a common problem of many ASDs, such as proton-pump inhibitors (PPIs) and H2 -receptor antagonists (H2RAs). Potassium-competitive acid blockers (P-CABs) are expected to solve this continuing conundrum. This article examined major ASDs and compared them with placebo in terms of nocturnal acid-inhibitory effects, using a network meta-analysis of randomized controlled trials (RCTs). To compare the effectiveness of major ASDs, a Bayesian network meta-analysis (NMA) was applied to process data extracted from RCTs. The plausible ranking for each regimen and some subgroups were assessed by surface under the cumulative ranking curves (SUCRA). Fifty-five RCTs were conducted with 2015 participants. In terms of nocturnal acid-inhibitory effects, the overall results showed that tegoprazan (SUCRA 91.8%) and vonoprazan (SUCRA 91.0%) had the best performance, followed by new PPIs (including tenatoprazole and ilaprazole) (SUCRA 76.6%), additional H2RAs once at bedtime (AHB) (SUCRA 61.3%), isomer PPIs (including esomeprazole and dexlansoprazole) (SUCRA 38.6%), revaprazan (SUCRA 34.7%), traditional PPIs (including omeprazole, rabeprazole, pantoprazole, lansoprazole) (SUCRA 32.6%), H2RAs (SUCRA 23.1%), and placebo (SUCRA 0.3%). In some subgroups, the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan was better than most of the other regimens, even new PPIs and AHB. This is the first study to compare the effect of ASDs on inhibiting nocturnal acid breakthrough. Overall, in terms of nocturnal acid-inhibitory effect, vonoprazan and tegoprazan had an advantage against other regimens including H2RAs, isomer PPIs, traditional PPIs, AHB, and new PPIs. Even in some subgroups, such as language classification (English), types of study design (crossover-RCT), age (≤40 years), BMI (18.5-24.9 kg/m2 ), continent (Asia and North America), disease status (health), the duration of therapy (2 weeks), and time of administration (at daytime or at night-time), the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan were better than most regimens, even AHB and new PPIs.

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

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

Knowledge, Attitude and Practices of Resident Doctors Towards use of Proton Pump Inhibitors in A Tertiary Care Hospital in Pune, India: A Cross-Sectional Survey

Background and Objectives: The most commonly prescribed drugs in healthcare systems are proton pump inhibitors (PPIs). Several studies have found that globally PPIs are frequently used without proper justification. Appropriate and updated knowledge about PPI among medical professionals is essential to enhance the rationale of PPI application. The present study with this goal was initiated to evaluate the understanding and behavioral practices toward PPI use among resident doctors in a tertiary care teaching hospital in Pune, western India. Method: A cross sectional survey using structured questionnaire. Results: The questionnaire was completed by 137 resident doctors. 82.5% of them prescribed acid-suppressing drugs for acute gastritis and other drugs in combination with them as the most common indications for the majority of their patients. These prescriptions were based on the consultant's or unit's policy, and resident doctors were not given the liberty to breach this policy. 71.5% of the respondents chose PPIs as their first choice, and 75.1% preferred the oral route. 10.2% of them claimed to have encountered a PPI-related adverse event. Despite the fact that 75.9% of the respondents preferred to prescribe PPIs for short durations, a lack of awareness about the possible risks associated with chronic PPI use was noted. 58.4% of resident doctors preferred using the step-down strategy, but 19.7% of participants were unaware of step up or step down when prescribing PPIs. The concept of drug interactions with the co-administration of PPI was also less understood by study participants. Conclusion: In the present survey study participants had less knowledge on correct indications for PPI usage as they fared PPI over any other acid-reducing medications to majority of their patients. There was also a lack of understanding of PPI adverse drug reactions, drug-drug interactions, and specific PPI administration approaches.

History and Pharmacological Mechanism of Gastric Acid-suppressive Drugs

Gastric acid-related disorders are commonly encountered in clinical practice. Acetylcholine, gastrin, and histamine are physiological agonists that stimulate acid secretion from parietal cells. Histamine plays a decisive role in the transformation of parietal cells into acid-secreting forms. The H&lt;sup&gt;+&lt;/sup&gt;, K&lt;sup&gt;+&lt;/sup&gt;- ATPase proton pump, which represents the final step of acid secretion, translocates from cytoplasmic tubulovesicles to secretory canaliculi upon parietal cell stimulation and facilitates exchange of intracellular H&lt;sup&gt;+&lt;/sup&gt; with extracellular K&lt;sup&gt;+&lt;/sup&gt; in a 1:1 ratio. Histamine-2 receptor antagonists and proton pump inhibitors (PPIs) are widely used in clinical practice, and potassium-competitive acid blockers (P-CABs) have gained attention in recent times. P-CABs address the unmet needs of patients who receive conventional PPIs and have broadened the spectrum of drug choices; however, further research is warranted to confirm long-term safety of these drugs. Comprehensive understanding of the mechanisms of actions, characteristics, advantages and disadvantages, and the adverse effect profile is essential for appropriate prescription of gastric acid-suppressive drugs. In this review, we provide a developing history and outline the pharmacological mechanisms underlying various gastric acid-suppressive drugs used in clinical settings.

Proton pump inhibitor has no effect in the prevention of post-endoscopic sphincterotomy delayed bleeding: a prospective randomized controlled trial.

Bleeding is one of the common adverse events of endoscopic retrograde cholangiopancreatography (ERCP), which is mainly caused by endoscopic sphincterotomy (EST). At present, it remains unclear whether proton pump inhibitor (PPI) should be used to prevent post-EST bleeding. Therefore, we performed a randomized controlled trial to investigate whether PPI is effective in the prevention of post-EST delayed bleeding. Consecutive eligible patients were randomly assigned (1:1) to experimental group (PPI group) or control group (normal saline, NS group). The patients in PPI group received intravenous esomeprazole 40 mg and normal saline 100 mL every 12 h for 2 days after ERCP immediately, and followed by oral esomeprazole (Nexium) 20 mg once a day for 7 days. Correspondingly, patients in the control group received intravenous normal saline 100 mL and did not take PPIs or any acid-suppressing drugs during hospitalization and after discharge. All patients were followed up for 30 days after ERCP. The primary endpoint was the incidence and severity of post-EST delayed bleeding. Between July 2020 and July 2022, 290 patients were randomly assigned to PPI group (n = 146) or NS group (n = 144). 5 patients from each group were excluded from the final analysis. There were 6 patients with post-EST delayed bleeding, with an incidence rate of 2.14%. The median time of delayed bleeding was 2.5 days after ERCP. 3 cases (2.12%, 3/141) occurred in the PPI group, with 1 case of mild and 2 cases of moderate bleeding. 3 cases (2.16%, 3/139) occurred in the NS group, with 2 cases of mild and 1 case of moderate bleeding. There was no significant difference in the incidence and the severity of post-EST delayed bleeding between the two groups (p = 1.000). Prophylactic use of PPI after EST does not reduce the incidence and severity of post-EST delayed bleeding in patients. https://www.chictr.org.cn/searchproj.aspx, identifier ChiCTR2000034697.

Post-Stroke Infections: Insights from Big Data Using Clinical Data Warehouse (CDW).

This study analyzed a digitized database of electronic medical records (EMRs) to identify risk factors for post-stroke infections. The sample included 41,236 patients hospitalized with a first stroke diagnosis (ICD-10 codes I60, I61, I63, and I64) between January 2011 and December 2020. Logistic regression analysis was performed to examine the effect of clinical variables on post-stroke infection. Multivariable analysis revealed that post-stroke infection was associated with the male sex (odds ratio [OR]: 1.79; 95% confidence interval [CI]: 1.49-2.15), brain surgery (OR: 7.89; 95% CI: 6.27-9.92), mechanical ventilation (OR: 18.26; 95% CI: 8.49-44.32), enteral tube feeding (OR: 3.65; 95% CI: 2.98-4.47), and functional activity level (modified Barthel index: OR: 0.98; 95% CI: 0.98-0.98). In addition, exposure to steroids (OR: 2.22; 95% CI: 1.60-3.06) and acid-suppressant drugs (OR: 1.44; 95% CI: 1.15-1.81) increased the risk of infection. On the basis of the findings from this multicenter study, it is crucial to carefully evaluate the balance between the potential benefits of acid-suppressant drugs or corticosteroids and the increased risk of infection in patients at high risk for post-stroke infection.

A66 PROTON PUMP INHIBITORS AND THE RISK OF INFLAMMATORY BOWEL DISEASE: A REAL WORLD POPULATION-BASED COHORT STUDY

Abstract Background Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are acid suppressant drugs indicated in highly prevalent conditions such as gastroesophageal reflux disease and peptic ulcer disease. A recent observational study reported an increased risk of inflammatory bowel disease (IBD) with the use of PPIs. However, this association may have been driven by certain methodological shortcomings, such as failure to properly account for protopathic bias, a conclusion-altering bias. Purpose To determine whether the use of PPIs compared with the use of H2RAs is associated with an increased risk of IBD. Method Using the longitudinal primary care records from the United Kingdom Clinical Practice Research Datalink database, we identified 1,498,416 initiators of PPIs and 322,474 initiators of H2RAs from January 1, 1990, through December 31, 2018, with follow-up until December 31, 2019. Standardized morbidity ratio weighted Cox proportional hazards models were used to estimate marginal hazard ratios (HRs) and 95% confidence intervals (CIs). Patients were analyzed according to the timing of the IBD events after treatment initiation (early versus late). In the early-event analysis, IBD events were assessed within the first two years of treatment initiation, an analysis subject to potential protopathic bias. In the late-event analysis, all exposures were lagged by two years to account for latency and minimize protopathic bias. Result(s) In the early-event analysis, the use of PPIs was associated with an increased risk of IBD within the first two years of treatment initiation, compared with H2RAs (HR: 1.39, 95% CI: 1.14-1.69). In contrast, the use of PPIs was not associated with an increased risk of IBD in the late-event analysis (HR: 1.05, 95% CI: 0.90 to 1.22). The results remained consistent in several sensitivity analyses. Image Conclusion(s) Compared with H2RAs, PPIs were not associated with an increased risk of IBD, after accounting for protopathic bias. Please acknowledge all funding agencies by checking the applicable boxes below CIHR Disclosure of Interest R. Yanofsky: None Declared, D. Abrahami Employee of: pfizer, R. Pradhan: None Declared, H. Yin: None Declared, E. McDonald: None Declared, A. Bitton Consultant of: Member of Advisory Boards for Abbie, Pfizer, Takeda, Jansen, and Merck, Speakers bureau of: Has received speaker fees for Abbie, Jansen, Takeda, and Pfizer, L. Azoulay Consultant of: Has received consults fees from Jansen, Pfizer, and Roche, Speakers bureau of: Has received speaker fees from Jansen, Pfizer, and Roche

Discovery of novel potassium-competitive acid blockers: Protonated form of ligand-receptor complex system.

Potassium-competitive acid blockers (P-CABs) are acid-suppressing drugs targeting the gastric proton pump (H+,K+-ATPase). They are able to mediate the electro-neutral exchange of H+ and K+ coupled with ATP hydrolysis. Because the conditions of both the cytoplasmic side (pH ∼7) and extracytoplasmic side (pH ∼1) of the target H+,K+-ATPase is are quite different, putting into consideration the moderate protonated forms of both the target protein and the P-CABs is important for system modeling. The three different protonated forms of the receptor models were evaluated with experimental data using docking and molecular dynamics. Here, we utilized the in-silico approaches to discover possible inhibitors against H+,K+-ATPase. Candidate substances were screened from the ChEMBL, Enamine, and Mcule databases. The high-throughput virtual screening (HTVS) was performed to screen for potent compounds. Molecular dynamics (MD) simulations were carried out among high docking scored candidates to validate the stability and binding affinity. These findings show that the proper modeling of the target-ligand complex is important for screening potent compounds, especially in extreme environments.