Type Of Proton Pump Inhibitors Research Articles

Proton pump inhibitors and gastrointestinal symptoms among patients with COVID-19 infection

Introduction The administration of proton pump inhibitors (PPIs) is anticipated to elevate an individual’s susceptibility to enteric infections as a result of altering the gut flora. The influence of PPIs on the clinical manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain. This study aims to investigate the impact of PPI usage on the clinical manifestation of COVID-19, namely its gastrointestinal symptoms. Methods This is a cross-sectional cohort study involving COVID-19 patients. Patients were interviewed using a predesigned questionnaire that asked about their demographics, clinical manifestations of COVID-19 infection, and the extent and type of PPIs in use. PPI usage was confirmed by reviewing patients’ electronic medical records. The primary outcome was to establish any association between the use of PPI and the symptoms and clinical presentation of COVID-19. Results Out of a total of 254 participants, 69 (27.2%) were considered PPI users. Patients who were on PPI medications reported a significantly lower rate of myalgia (27.5% vs 51.9%; p = 0.0006) and heartburn (5.7% vs 15.6%; p = 0.03) but had a significantly higher rate of abdominal pain (27.5% vs 13.5%; p = 0.001) and diarrhoea (28.9% vs 14.5%, p = 0.02) when compared to those who were not using PPIs. Patients on PPIs were also shown to have significantly higher odds of developing diarrhoea (OR 2.0, 95% CI: 1.08 to 3.93, p = 0.02) and abdominal pain (OR 2.0, 95% CI: 1.22 to 3.93, p = 0.03), but a lower risk of developing myalgia (OR 0.5, 95% CI: 0.3 to 0.9, p = 0.02) when compared to non-PPI users. Conclusion This study shows that the use of PPIs could impact COVID-19 clinical presentation toward more gastrointestinal manifestations. Further studies investigating the link between other acid suppression medications and COVID-19 manifestations and severity should be carried out.

Gastric Polyps in Long-Term Proton Pump Inhibitor Use: Identification of Risks and Characteristics.

Aim Estimate the prevalence of gastric polyps linked to long-term use of proton pump inhibitor (PPI), determine the various risk factors that promote this association, and identify the characteristics associated with these polyps. Methods This prospective cross-sectional study was conducted on approximately 1000 patients presenting to the Gastroenterology Endoscopic Department for upper GI endoscopy at two hospital centers in Beirut, Lebanon, over a period of 12 months from September 2021 to September 2022. The demographic and clinical data of patients who had been taking PPIs for at least one month were collected via a questionnaire. All patients with a previous Helicobacter pylori (H. pylori) infection, presence of hypergastrinemia, or a personal/family history of gastric polyps were excluded from this study. Statistical analyses were performed using SPSS 20 software. Categorical variables were compared by Fisher's exact test; p-values of less than 0.05 were considered statistically significant. Results The prevalence of gastric polyps linked to long-term PPI use was 30%. The minimum duration of daily PPI use required for the formation of polyps is around 24 months. The dosage did not play a significant role in increasing this prevalence. A significant correlation was found between chronic PPI use and factors such as sex, age range, duration, and type of PPI used. These polyps were predominantly found in females (with an OR of 2.9), increased with age, were mostly of the fundic gland type, and their size was proportionally linked to both the dosage and duration of daily PPI use. No cases of dysplasia within the fundic gland polyps (FGPs) were demonstrated in our study. Conclusion To date, there is no current data that prove an association between gastric cancer and PPI-induced FGPs. Additionally, the incidence of FGPs has increased with the widespread chronic use of PPIs. Therefore, attention should be drawn to the potential risk of dysplasia. Thus, the present study highlights the importance of limiting the prescription of PPIs to globally well-defined indications and determining the various risk factors that promote the association between gastric polyps and PPI use. This abstract was recently presented as an E-poster at the ESGE Days 2024 Congress on April 25-27, 2024, in Berlin, Germany.

#2824 Use of proton pump inhibitors is not associated with post-dialysis fatigue and time of recovery after dialysis in patients on chronic hemodialysis

Abstract Background and Aims Chronic hemodialysis is often associated with post-dialysis fatigue (PDF), a condition characterized by extreme tiredness and lack of energy. PDF is a debilitating symptom that significantly impairs quality of life of hemodialysis patients. Furthermore, PDF is independently associated with the time to recover after dialysis (TIRD), which can be used as an indirect measure of PDF. Recent studies have shown that the use of proton pump inhibitors (PPI) is independently associated with the prevalence and severity of fatigue in kidney transplant recipients. The aim of this study is to determine whether the use of PPIs in patients undergoing chronic hemodialysis is associated with PDF prevalence and characteristics, as well as the TIRD. Method For this retrospective study, we recruited patients undergoing chronic hemodialysis and asked open-ended questions about their post-dialysis fatigue and time of recovery. Each patient was asked to rate the intensity, duration and frequency of their PDF on a scale of 1 to 5. We defined whether patients used a PPI (no PPI use or PPI use), the type of PPI used, the dose of PPI used, and the duration of the PPI use (<1 year or ≥1year). Results The study analysed 346 patients, of whom 259 used PPIs (55 used omeprazole, 63 esomeprazole, 54 pantoprazole, 87 lansoprazole, and 7 rabeprazole) and 87 did not. Among the patients, 232 reported suffering from PDF, while 114 did not. The median [min-max] TIRD was 210 minutes [0-1440]. The prevalence of PDF in PPI users and non-users was 67% and 68%, respectively (p= 0.878). There was no significant difference in the median [min-max] TIRD between PPI users and non-users (180 [0-1440] and 240 [0-1440], respectively; p=0.871). Additionally, there was no significant difference in the median PDF intensity, duration, frequency, and severity PPI users and non-users. The prevalence of PDF was similar among the different types of PPI used and did not differ with respect to PPI non-users. Duration of PPI exposure was <1 year in 42 patients and ≥1 year in 224 patients. There was no difference in prevalence of PDF between the two exposures. The correlation matrix showed no statistical significance between PPI equivalent dose, treatment duration, PDF frequency, PDF characteristics, and TIRD. Conclusion There is no association between the use of PPIs and PDF or time of recovery after dialysis in patients on chronic hemodialysis.

Efficacy and Safety of Omeprazole for the Treatment of Acid Peptic Disorders: A Systematic Review and Meta-Analysis

Background Aim. To compare the efficacy of omeprazole to other proton-pump inhibitors (PPIs) or placebo for the treatment of acid peptic disorders (APDs) using a comprehensive literature search including hard-to-access journals and non-English articles. Methods. PubMed, Google Scholar, and China National Knowledge Infrastructure were searched (from inception to March 2023) for trials comparing omeprazole to other types of PPIs or placebo for the treatment APD. Efficacy was analyzed separately for erosive diseases and nonerosive diseases. Primary outcomes included improvement of APD symptoms and frequency of ulcer or erosion healing. Secondary outcomes included adverse events, cost effectiveness, nocturnal acid breakthrough, and length of stay if hospitalized. Random and fixed-effects models were used to determine estimates of efficacy. Results. Thirty-one eligible trials (N = 10,539 participants) were analyzed, including 12 articles not typically included in previous reviews due to translation or journal access issues. Omeprazole significantly improved heartburn compared to placebo (RR = 2.47, 95% CI: 2.13 and 2.86, and p<0.001) and was equivalent to the other five types of PPI. Omeprazole had significantly fewer patients reporting adverse events versus placebo (11% versus 31%, respectively) and other PPIs. Omeprazole was the most cost-effective PPI compared to the other types of PPIs in India. Conclusions. Omeprazole continues to be an effective proton-pump inhibitor to treat patients with acid peptic disorders and was well tolerated. Omeprazole was significantly better than placebo and was equivalent with other PPIs for curing heartburn and was equivalent to other PPIs for the healing of ulcers or erosions in addition to being the most cost-effective.

Prescribing Portraits to Optimize Prescribing of Proton Pump Inhibitors in Long-Term Care: PPI-T STOP Study.

Proton pump inhibitors (PPIs) are among the most commonly prescribed medications in Canada, particularly for older adults (at least 65 years of age). Overprescribing of long-term PPIs leads to health care system waste and is associated with adverse effects, including infections and fractures. The high prevalence of PPI prescribing in long-term care (LTC) facilities prompted an evaluation of systematic approaches to PPI deprescribing. To assess the impact of individualized prescribing portraits, a type of audit-and-feedback quality improvement intervention, on PPI deprescribing in the LTC setting. This prospective, nonblinded, uncontrolled, pre-post quality improvement study was conducted from December 2021 to April 2022 at a 126-bed LTC facility in Vancouver, British Columbia. A PPI prescribing portrait was developed for each prescriber (n = 5) at the LTC facility, containing the prescriber's personal PPI prescribing metrics as compared with those of their peers across all LTC facilities within the same health authority; an evidence summary for PPI deprescribing; and a personalized list of the prescriber's PPI-treated residents, along with their respective PPI indications and strategies for PPI deprescribing. Three months after the prescribers received their PPI prescribing portraits, the number and types of PPI deprescribing orders were recorded. The implementation of prescribing portraits resulted in 17 (61%) of 28 PPI-treated residents receiving a deprescribing order by the end of the study period. Of the 28 PPI-treated residents, 20 were determined to be eligible for PPI deprescribing according to the evidence summary presented in the prescribing portrait; of these 20 residents, 16 (80%) appropriately received PPI deprescribing. Individualized prescribing portraits had the potential to increase evidence-based PPI deprescribing among LTC residents, beyond the extent of deprescribing previously achieved through standard of care.

Independent Risk Factors Predicting Eradication Failure of Hybrid Therapy for the First-Line Treatment of Helicobacter pylori Infection.

Hybrid therapy is a recommended first-line anti-H. pylori treatment option in the American College of Gastroenterology guidelines, the Bangkok Consensus Report on H. pylori management, and the Taiwan H. pylori Consensus Report. However, the cure rates of eradication therapy in some countries are suboptimal, and the factors affecting the treatment efficacy of hybrid therapy remain unclear. The aim of this study is to identify the independent risk factors predicting eradication failure of hybrid therapy in the first-line treatment of H. pylori infection. A retrospective cohort study was conducted on 589 H. pylori-infected patients who received 14-day hybrid therapy between September 2008 and December 2021 in ten hospitals in Taiwan. The patients received a hybrid therapy containing a dual regimen with a proton pump inhibitor (PPI) plus amoxicillin for an initial 7 days and a quadruple regimen with a PPI plus amoxicillin, metronidazole and clarithromycin for a final 7 days. Post-treatment H. pylori status was assessed at least 4 weeks after completion of treatment. The relationships between eradication rate and 13 host and bacterial factors were investigated via univariate and multivariate analyses. In total, 589 patients infected with H. pylori infection were included in the study. The eradication rates of hybrid therapy were determined as 93.0% (95% confidence interval (CI): 90.9-95.1%), 94.4% (95% CI: 93.8-97.2%) and 95.5%% (95% CI: 93.8-97.2%) by intention-to-treat, modified intention-to-treat and per-protocol analyses, respectively. Univariate analysis showed that the eradication rate of clarithromycin-resistant strains was lower than that of clarithromcyin-susceptible strains (83.3% (45/54) vs. 97.6%% (280/287); p < 0.001). Subjects with poor drug adherence had a lower cure rate than those with good adherence (73.3% (11/15) vs. 95.5% (534/559); p = 0.005). Other factors such as smoking, alcohol drinking, coffee consumption, tea consumption and type of PPI were not significantly associated with cure rate. Multivariate analysis revealed that clarithromcyin resistance of H. pylori and poor drug adherence were independent risk factors related to eradication failure of hybrid therapy with odds ratios of 4.8 (95% CI: 1.5 to 16.1; p = 0.009) and 8.2 (95% CI: 1.5 to 43.5; p = 0.013), respectively. A 14-day hybrid therapy has a high eradication rate for H. pylori infection in Taiwan, while clarithromycin resistance of H. pylori and poor drug adherence are independent risk factors predicting eradication failure of hybrid therapy.

Is open-capsule proton pump inhibitor associated with faster healing time for marginal ulceration after Roux-en-Y gastric bypass?

BackgroundMarginal ulceration (MU) is a significant cause of morbidity after Roux-en-Y gastric bypass (RYGB). Proton pump inhibitors (PPIs) are the primary treatment. Prior limited data suggest that open-capsule PPIs (OC-PPIs) improve MU healing compared with intact-capsule PPIs (IC-PPIs), necessitating further validation. ObjectivesWe aimed to compare healing times of MU after RYGB when treated with OC-PPIs versus IC-PPIs. SettingTertiary academic center, United States. MethodsWe retrospectively analyzed patients with prior RYGB diagnosed with MU from 2012 to 2022. Patients requiring mechanical closure without documented healing and without clear PPI prescriptions were excluded. The primary outcome was time to ulcer healing. Log-rank testing and Kaplan–Meier survival curve analyses were performed to compare MU healing times when treated with OC-PPIs versus IC-PPIs. Subgroup analyses further characterized ulcer healing times based on type and dosage of PPI used. ResultsA total of 108 patients were included for final analysis (38 received OC-PPIs and 70 received IC-PPIs). Treatment with OC-PPIs significantly decreased MU healing time compared with IC-PPIs (146.18 versus 226.14 d; p = .018). However, when stratified by PPI potency, the positive effect of opening the capsule lost significance. ConclusionIn this study, OC-PPIs significantly improved MU healing times compared with IC-PPIs in RYGB patients, consistent with prior data. However, on subgroup analysis comparing therapy with similar PPI potency, the MU healing time did not differ with respect to administration method. These results highlight the need for a prospective randomized trial to compare the true effect of administration method.

Production of an O-desmethylated product, a major human metabolite, of rabeprazole sulfide by bacterial P450 enzymes

Rabeprazole is a common type of proton pump inhibitor (PPI) used to treat various peptic disorders. Unlike most PPI drugs, rabeprazole is spontaneously reduced to rabeprazole sulfide (thioether) when it is given to patients. As a result, rabeprazole sulfide is considered one of the active metabolites of rabeprazole. Rabeprazole sulfide is mainly metabolized to desmethyl rabeprazole sulfide by CYP2C19 and CYP2D6 in people. However, the pharmacological efficacy and safety of desmethyl rabeprazole sulfide have not yet been investigated. Its usage is challenging due to the high cost associated with the drug. In this study, we found CYP102A1 mutants that can produce desmethyl rabeprazole sulfide as a major metabolite of rabeprazole sulfide. The chemical characteristics of the major product were confirmed using high-performance liquid chromatography, LC-mass spectrometry, and nuclear magnetic resonance spectroscopy. CYP102A1 mutants R47L/F87V/L188Q, R47L/F87V/L188Q/A335V/Q359R, and R47L/F87V/L188Q/I254V/D351E showed kcat values of 39, 93, and 88 min−1, respectively, for O-desmethylation of rabeprazole sulfide. Furthermore, the highest concentration of desmethyl rabeprazole sulfide product from 2 mM rabeprazole sulfide at optimal conditions was obtained in bacterial whole-cell biotransformation with the R47L/F87V/L188Q mutant, reaching 0.63 mM at 4-h incubation. In conclusion, we present a platform that facilitates the efficient and sustainable production of the desmethylated product from rabeprazole sulfide for use in the biopharmaceutical industry.

Proton Pump Inhibitors Usage Among Discharged Patients in a Tertiary Care Hospital- An Observational Study

Background: Proton pump inhibitors (PPI) have reportedly been used in inappropriate clinical settings, often leading to an increased risk of adverse effects, drug interactions, and costs. Aim: The aim of this study was to evaluate the appropriateness of PPI prescription on discharge of patients in medicine ward of a tertiary care hospital in Bangladesh. Methods: A cross-sectional study was done for 3 months in the department of medicine in a tertiary care hospital to evaluate the indications of PPI use, appropriateness of PPI use and types of PPI prescribed. A total of 107 patients who were prescribed PPI on discharge were enrolled after written informed consent and data were collected in a structured questionnaire. Results: Among the 107 patients discharged, 64 were males and 43 were females. The mean age was 51.3 ±17.6 (SD) years.Among the study population, 49 were appropriately prescribed PPI and 58 were inappropriately prescribed PPI. Regarding indications, 53.1% received PPI for prevention of anti-platelet induced gastric erosion and 18.9% were prescribed PPI for no apparent reason. Age (p=0.199) and gender (p=0.605) was not significantly associated with the appropriate prescription of PPI.Of the various preparations of PPI prescribed, esomeprazole was prescribed in most of the discharged patients (56%). Conclusion: this study demonstrates the existence of an over-prescription of PPI. PPI prescription needs to be improved, thereby reducing drug interactions, adverse effects and unnecessary economical expenses. J MEDICINE 2023; 24(2): 125-130

Unnecessary Prescription of Proton Pump Inhibitors (PPI): An Analysis of Inpatient Discharge Practices

Background: Proton pump inhibitors (PPI) have reportedly been used in inappropriate clinical settings, often leading to an increased risk of adverse effects, drug interactions, and costs. Aim: The aim of this study was to evaluate the appropriateness of PPI prescription on discharge of patients in medicine ward of a tertiary care hospital in Bangladesh. Methods: A cross-sectional study was done for 3 months in the department of medicine in a tertiary care hospital to evaluate the indications of PPI use, appropriateness of PPI use and types of PPI prescribed. A total of 107 patients who were prescribed PPI on discharge were enrolled after written informed consent and data were collected in a structured questionnaire. Results: Among the 107 patients discharged, 64 were males and 43 were females. The mean age was 51.3 ±17.6(SD) years.Among the study population, 49 were appropriately prescribed PPI and 58 were inappropriately prescribed PPI. Regarding indications, 53.1% received PPI for prevention of anti-platelet induced gastric erosion and 18.9% were prescribed PPI for no apparent reason. Age (p=0.199) and gender (p=0.605) was not significantly associated with the appropriate prescription of PPI.Of the various preparations of PPI prescribed, esomeprazole was prescribed in most of the discharged patients (56%). Conclusion: This study demonstrates the existence of an overprescription ofPPI. PPI prescription needs to be improved, thereby reducingdrug interactions, adverse effects and unnecessary economical expenses. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 202

Clinical Characteristics of Peptic Ulcer Disease &amp; its Pharmacological Management in Primary Care

Background: Peptic ulcer diseases (PUD) are common conditions reported in daily clinical practice. Proton pump inhibitors (PPIs) are the most potent pharmacological inhibitors of gastric acid secretion. Aims &amp; objectives: This study aimed to evaluate &amp; understand the clinical presentation and management of PUD with PPIs in general practice. Methods: This prospective study was conducted on 150 diagnosed cases of PUD patients in a single center of private practice in rural areas from February 2022 to August 2022. Patients were enrolled by following inclusion &amp; exclusion criteria with informed written consent. Eight (08) weeks after the completion of treatment by giving PPIs, a repeat endoscopy was done to see the improvement of healing of the ulcer. All data were collated and results were expressed in percentages which are illustrated in different tables &amp; figures. Results: Among 150 endoscopically diagnosed PUD patients major age group was 31-40 years (50%) of both sexes where the male (58.66%) were more predominant. Abdominal pain (82%), heartburn (56.66%), etc were the main clinical symptoms of the patients who were referred for endoscopy. After confirming the diagnosis, PPIs were given to the patients. Esomeprazole (34.66%), lansoprazole (22%), pantoprazole (18.66%), etc were prescribed frequently. After 8 weeks of treatment, repeat endoscopy revealed that the ulcer was completely healed in 65.33% of patients whereas only 6.66% had no improvement. Conclusion: The majority of the patient are almost cured of PUD by receiving various types of PPIs which are very effective drugs for healing peptic ulcer disease. Mediscope 2023;10(1): 22-30

Effects of postoperative use of proton pump inhibitors on gastrointestinal bleeding after endoscopic variceal treatment during hospitalization.

Endoscopic variceal treatment (EVT) is recommended as the mainstay choice for the management of high-risk gastroesophageal varices and acute variceal bleeding in liver cirrhosis. Proton pump inhibitors (PPIs) are widely used for various gastric acid-related diseases. However, the effects of PPIs on the development of post-EVT complications, especially gastrointestinal bleeding (GIB), remain controversial. To evaluate the effects of postoperative use of PPIs on post-EVT complications in patients with liver cirrhosis during hospitalization. Patients with a diagnosis of liver cirrhosis who were admitted to the Department of Gastroenterology of the General Hospital of Northern Theater Command, treated by an attending physician between January 2016 and June 2020 and underwent EVT during their hospitalization were included. Logistic regression analyses were performed to explore the effects of postoperative use of PPIs on the development of post-EVT complications during hospitalization. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A total of 143 patients were included. The incidence of post-EVT GIB and other post-EVT complications was 4.90% and 46.85%, respectively. In the overall analyses, postoperative use of PPIs did not significantly reduce the risk of post-EVT GIB (OR = 0.525, 95%CI = 0.113-2.438, P = 0.411) or other post-EVT complications (OR = 0.804, 95%CI = 0.413-1.565, P = 0.522). In the subgroup analyses according to the enrollment period, type and route of PPIs after the index EVT, use of PPIs before the index EVT, use of vasoactive drugs after the index EVT, indication of EVT (prophylactic and therapeutic), and presence of portal venous system thrombosis, ascites, and hepatocellular carcinoma, the effects of postoperative use of PPIs on the risk of post-EVT GIB or other post-EVT complications remain not statistically significant. Routine use of PPIs after EVT should not be recommended in patients with liver cirrhosis for the prevention of post-EVT complications during hospitalization.

Helicobacter pylori Empirical and Tailored Eradication Therapy and Factors Influencing Eradication Rate: a 4-Year Single-Center Study.

The Helicobacter pylori eradication rate with standard triple therapy (STT) is continuously decreasing due to clarithromycin resistance. This study aimed to investigate the eradication rate of empirical and tailored therapy and explore various factors affecting this eradication rate using clarithromycin resistance test data for the last 4 years at a single institution in Daegu. From August 2018 to July 2021, a total of 1,395 patients diagnosed with H. pylori infection based on rapid urea testing and histology at Keimyung University Dongsan Hospital were retrospectively examined. Participants were classified into the empirical and tailored therapy groups according to the results of the clarithromycin resistance test using the polymerase chain reaction. The overall eradication rate of empirical STT was 72.8%, and the eradication rate by year was 71.6% in 2018, 77.4% in 2019, 70.3% in 2020, and 70.6% in 2021; the differences were not statistically significant (p = 0.173). No significant difference was noted in the eradication rate according to gender, age, type of proton pump inhibitors, and use of probiotics. Significant differences were noted in the eradication rate according to the treat-ment period: 69.7% in the 7-day, 67.3% in the 10-day, and 81.4% in the 14-day group (p = 0.001). The eradication rate with STT was 87.4% in the non-resistant group. In the case of clarithromycin resistance, treatment was mainly with bismuth quadruple therapy (BQT), and the eradication rate was 86.1%. The eradication rate was higher with administration of BQT for 10 days or 14 days than for administration of BQT for 7 days, but with no statistical significance (p = 0.364). Extending the treatment period of STT helped in improving the eradication rate, and tailored therapy through clarithromycin resistance testing showed superior results when compared to empirical therapy.

Effect of proton pump inhibitors on the risk of chronic kidney disease: A propensity score-based overlap weight analysis using the United Kingdom Biobank.

Background: Proton pump inhibitors (PPIs) are widely used and have been linked to kidney diseases. However, the role of PPI use in the development of chronic kidney disease (CKD) remains unclear. We undertook this study to examine the association between PPI use and the subsequent risk of CKD. Methods: This is a prospective analysis of 462,421 participants free of cancer diagnosis or chronic kidney disease from the United Kingdom Biobank. Self-reported PPI use was recorded using an electronic questionnaire and confirmed by a trained staff. Incident CKD was identified based on the medical history. Overlap propensity score weighting with the Cox model was used to calculate the effect of PPI use on CKD risk. The number needed to harm (NNH) was calculated at 5 and 10years of follow-up. Results: We documented 7,031 cases of CKD over a median follow-up of 8.1years. Overlap propensity score weighting analysis showed that regular PPI users had a 37% higher risk of CKD incident than non-users (HR 1.37, 95% CI 1.28-1.47). The association persisted across subgroup analyses, different types of PPIs, and several sensitivity analyses. Quantitative bias analysis indicated that the result was robust to unmeasured confounding (E-value 2.08, lower 95% CI 1.88). The NNH was 147.9 and 78.6 for 5 and 10years of follow-up, respectively. A head-to-head comparison showed that PPI users had a 19% higher risk of CKD than H2RA users (HR 1.19, 95% CI 1.02-1.39). Conclusion: The regular use of PPI is associated with a higher risk of CKD. Healthcare providers should carefully weigh up the potential benefits against the risk in prescribing PPIs, particularly for patients requiring long-term treatment.

Acid suppressants use and risk of atherosclerotic cardiovascular disease in middle-aged and older adults

Background and aimsConcerns regarding adverse events associated with the use of acid suppressants have increased. However, the impact of proton pump inhibitors (PPIs) and histamine‐2 receptor antagonists (H2RAs) on the risk of atherosclerotic cardiovascular disease (ASCVD) remains unknown. This study aimed to estimate the risk of ASCVD in association with the use of PPIs and H2RAs. MethodsThis prospective cohort study included participants without cardiovascular diseases or anti-hypertensive treatment at baseline (2006–2010) in the UK Biobank. The outcomes were ASCVD and each subtype (coronary artery disease, myocardial infarction, peripheral artery disease, and ischemic stroke). The association was estimated by Cox proportional-hazards models. ResultsAmong 316,730 individuals (aged 50–88 years), during a median of 12.5 years of follow-up, we documented 13,503 (4.3%) incident ASCVD. Regular PPIs use was associated with a higher risk of ASCVD (HR: 1.16, 95% CI: 1.09–1.23) and every subtype of ASCVD. Among each type of PPIs, omeprazole (HR: 1.19, 95% CI: 1.11–1.28), lansoprazole (HR: 1.11, 95% CI: 1.02–1.22), and pantoprazole (HR: 1.40, 95% CI: 1.00–1.97) were associated with a higher risk of ASCVD. Stratification analysis showed that PPIs use was associated with a higher risk of ASCVD among individuals without indications of medications for PPIs. In addition, use of H2RAs was not related to the risk of ASCVD (HR: 0.97, 95% CI: 0.85–1.11). ConclusionsPPIs were associated with increased risk of ASCVD, particularly amongst participants without indications for medication. Our findings are of important practical significance and suggest that clinicians should be cautious in prophylactic use of PPIs.

Proton Pump Inhibitors Use and Increased Risk of Spontaneous Bacterial Peritonitis in Cirrhotic Patients: A Retrospective Cohort Analysis.

BackgroundSince their introduction in the early 1980s, proton pump inhibitors (PPIs) have been used worldwide for a broad range of indications. Unfortunately, however, PPIs have become overly prescribed by healthcare providers, sometimes in the absence of clear indications. Although PPIs were initially presumed to have an excellent safety profile, emerging studies have shed light on the association between their long-term use and a myriad of side effects, including the possibility of an increased risk of spontaneous bacterial peritonitis (SBP). Data available to date regarding the association between PPI use and SBP development in cirrhotic patients is conflicting. While some observational studies provide no association between PPI use in cirrhotic patients and an increased risk of SBP development, many others support this association. As a result of the conflicting conclusions from case controls, cohorts, and meta-analyses, we aimed to carry out this retrospective cohort analysis of data from cirrhotic patients included in the electronic medical record-based commercial database, EXPLORYS (IMB-WATSON, Cleveland, Ohio). Our aim was to evaluate for a possible association between PPIs use and the risk of SBP development in cirrhotic patients and to compare the prevalence of SBP development between cirrhotic patients who were actively using PPIs and those who were not.MethodsA retrospective cohort analysis with chart review was conducted on patients with cirrhosis who were included in the electronic medical record-based commercial database, EXPLORYS (IMB-WATSON, Cleveland, Ohio). Using this database, records were reviewed between December 2017 and 2020. Included patients were adults aged 30 to 79 years with a Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) diagnosis of liver cirrhosis. Included patients with a SNOMED-CT diagnosis of liver cirrhosis were divided into two groups: the first group included all cirrhotic patients who did not use PPIs and the second group included all cirrhotic patients who were on PPIs at home.ResultsIn our analysis, SBP occurred in 1.7% (1,860 patients) of the included cirrhotic patients whether they were actively taking PPIs or not. Among the 40,670 cirrhotic patients who were on PPIs at home, 1,350 (3.3%) patients developed SBP. On multivariate analysis, PPI use was the strongest predictor for SBP in cirrhotic patients (odds ratio (OR) = 4.24; 95% confidence interval (CI): 3.83 - 4.7, P value < 0.0001), with cirrhotic patients taking PPIs being 4.24 more likely to develop SBP than those not on PPIs. In addition, PPI use, history of bleeding varices, age, race, and gender were found to be independent predicting factors for SBP, in descending order of importance.ConclusionsOur retrospective cohort analysis has shown that the use of PPIs in patients with liver cirrhosis is an independent predicting risk factor for SBP development. It solidified the argument that cirrhotic patients receiving this form of therapy seem to have a higher risk of developing SBP. In the setting of the emerging evidence that PPIs might impose health risks in cirrhotic patients, further studies are needed to settle the current debate between supporters and opponents of this proposition. In addition, future studies may help clarify the relationship between the occurrence of SBP in cirrhotic patients and the type, dose, and duration of PPIs used. We recommend that unless it is clearly indicated, PPI therapy should be avoided or administered with caution in patients with cirrhosis.

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.

Trends in proton pump inhibitor use, reflux esophagitis, and various upper gastrointestinal symptoms from 2010 to 2019 in Japan.

The increasing usage of proton pump inhibitors (PPIs) has been reported worldwide, but information on PPI use in East Asia is inadequate. This study aimed to examine the trends in PPI use in Japan, along with the changes in histamine H2 receptor antagonist (H2RA) use, disease rate of reflux esophagitis, and the prevalence of upper gastrointestinal symptoms. We analyzed 217,712 healthy subjects (127,607 men and 90,105 women; 51.4 ± 9.7 years old) participating in the health check program from 2010 to 2019. Various upper gastrointestinal symptoms were evaluated using the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) questionnaire. Reflux esophagitis was diagnosed by esophageal erosion using the Los Angeles classification grades A, B, C, and D. From 2010 to 2019, the percentage of PPI users increased markedly from approximately 1.8% to 5.3%, whereas that of H2RA users decreased gradually from approximately 2.5% to 1.9%. The use of all classical types of PPIs (omeprazole, lansoprazole, rabeprazole, and esomerazole) and a new type of PPI, a potassium-competitive acid blocker (vonoprazan), greatly increased during the 10 years. An upward trend in the prevalence of reflux esophagitis was observed from 2010 to 2015, but not from 2016 to 2019, indicating that the monotonic rising prevalence of reflux disease stopped in the middle of the 2010s in Japan. In contrast, various upper gastrointestinal symptoms significantly improved between 2010 and 2019. All 12 FSSG symptoms of PPI users were significantly worse than those of non-PPI users, suggesting that PPIs still cannot completely control upper gastrointestinal symptoms. In conclusion, this study revealed a significant increase in PPI use and a slight decrease in H2RA use from 2010 to 2019. Despite a plateau in the prevalence of reflux esophagitis and considerable improvement in various upper gastrointestinal symptoms, PPI use has continued to increase in Japan.

A129 CYP2C19 PHARMACOGENETIC TESTING IN PAEDIATRIC PATIENTS WITH EOSINOPHILIC ESOPHAGITIS INFLUENCES DOSING OF PROTON-PUMP-INHIBITORS AND RESPONSE TO THERAPY

BackgroundEosinophilic esophagitis (EoE) is a chronic inflammatory disorder that can be treated with a proton pump inhibitor (PPI). Pharmacogenetics (PGx) is the study of how variations in an individual’s genome influences drug response. Genetic variation in the metabolism gene CYP2C19 can produce differences in enzyme activity which is known to be a contributing factor for therapeutic failure with PPI treatment. Use of 2nd generation PPI (rabeprazole) can be beneficial in some as this PPI is less effected by CYP2C19 metabolism. PGx has been studied in PPI therapy for peptic ulcer disease but has not been demonstrated in patients with EoE.AimsTo describe the CYP2C19 metabolism in patients with EoE on PPI and to estimate the clinical utility of PGx testing in directing subsequent changes in therapy with improvement in remission rates.MethodsInterim analyses of a single centre, non-interventional, ongoing descriptive pilot study investigating CYP2C19 metabolism in patients with EoE, as part of a larger PGx pilot study and EoE- AHEAD Registry Study at SickKids. Patients with EoE that were newly diagnosed and started PPI or those not in remission on current non-PPI therapy or not in remission on dose PPI (2 mg/kg/day, max 30 mg lansoprazole BID) were included. Active disease was defined as a peak eosinophil count >15/hpf.Results37 patients met the inclusion criteria with completed PGx test; mean age was 13 years, 29(78%) were male, and 13(35%) had concurrent atopic disease. PGx testing showed that 12(32%) and 4(11%) were rapid (RM) and ultrarapid metabolizers (URM) respectively (Fig.1), which is significantly higher than the population average. Of this subgroup, 9 started rabeprazole, 3 had a lansoprazole dose increase, and 4 had no changes. Overall, changes in therapy based on PGx testing were made in 29(78%) patients, 8 are awaiting follow-up (Fig 2). Currently, the patients with available repeat biopsy results after PGx test-guided therapy changes is limited due COVID-19 related delays in endoscopies.ConclusionsThe preliminary findings of our study using PGx to guide PPI dosing in pediatric patients with EoE demonstrate that PGx test results lead to a change in clinical management in most patients. In RM and URM, PGx results trigger an adjustment of PPI dose or type could lead to earlier disease remission in PPI-responsive patients, thereby optimizing PPI efficacy. PGx may support dose reduction in poor metabolizers aiming to avoid long-term adverse events.Further correlation with endoscopy and histology findings of patients after PGx-guided therapy changes will follow. Furthermore, it is important to examine if CYP2C19 variant information available before PPI therapy further streamlines an initial phase of the treatment. Funding AgenciesDr. Marcon: J Garfield Campbell Fund, Dr. Hulst: Start-up Funds from the Department of Pediatrics at SickKids

Evaluate the effectiveness and safety of proton pump inhibitors (PPIs) in the treatment of upper GIT disorders

Introduction: Proton pump inhibitors (PPIs) are most prescribed medication classes and have similar efficacy between generic and brand names. PPIs are used for treatment upper GIT disorders. The aim of the present study was to evaluate the effectiveness and safety of proton pump inhibitors (PPIs). Methods: A cross sectional study conducted randomly on pharmacies, patients and Doctors to collect a data regarding the effectiveness and safely use of PPI through predesigned questionnaire containing information about dosage, types, side effect, effectiveness and safety of PPIs. The collected data was analysis by using Chi-square for determine the significant differences at α &lt; 0.05. Result: The result of present study revealed numbers of points in which the questionnaire were intended for pharmacies, patients and doctors knowledge, effectiveness and safety of PPIs. The data gathered from pharmacy shown PPI dispensed without prescription (P&lt; 0.05) in dose of 20 mg of omeprazole and for treatment of gastritis, stomachache and on medication use (P&lt; 0.05). No side effect or any problem, safe, and effective of PPIs was from patients seeking PPIs to the drug dispensers. Furthermore, questionnaire for patients whom seeking treatment shown some similarity to pharmacies answers, however lack the knowledge about side effect of PPIs, and PPIs withdraw among patients. PPIs was found to be used by patients due to the advices of friends (P&lt; 0.05). The last part in this study was doctors involved in which some common similarity were also identified between doctors, patients and pharmacies responses. Although, Doctors responses were revealed that PPIs should be used by prescription in single dose of common types of PPIs (P&lt; 0.05). Conclusion: Due to the short time use of PPIs have been reported. This study suggested that, even no side effect and highly effective of PPIs reported, the PPIs should be monitoring and use under prescription.