The role of Helicobacter pylori (H. pylori) screening and eradication on reducing upper gastrointestinal bleeding (UGIB) complications after acute myocardial infarction (MI) is uncertain. The HELicobacter pylori screening to prevent gastrointestinal bleeding in patients with acute MI (HELP-MI SWEDEHEART) trial aims to determine whether systematic H. pylori screening compared to usual care reduces UGIB, mortality, and cardiovascular outcomes after MI.

A cluster randomized, crossover, registry-based clinical trial using SWEDEHEART as trial platform for study population definition and source for data collection in combination with nationwide Swedish health data registries. Thirty-five Swedish hospitals, organized into 18 clusters based on percutaneous coronary intervention networks, were randomized to either routine H. pylori screening for adults with acute type-1 MI or usual care. After 1 year, a 2-month blanking period was followed by a crossover to the alternate allocation for 1 year. The trial enrolment was concluded after one additional year of registry-based follow-up. The primary endpoint is UGIB. Secondary endpoints include all-cause death, cardiovascular death, readmission for MI, stroke, or heart failure. Endpoints will be reported combined (Net Adverse Clinical Events; Major Adverse Cardiac or Cerebrovascular Events) and separately. The primary analysis will include all available follow-up time corresponding to a maximum follow-up time of 3 years and 2 months.

HELP-MI SWEDEHEART aims to determine the utility of routine H. pylori screening to reduce UGIB and improve cardiovascular outcomes after MI. By integrating national registry follow-up data with a pragmatic trial design, it has the potential to provide evidence for the effect of the implementation of routine H. pylori screening as part of acute MI care.

ClinicalTrials.gov, NCT05024864.

Gastroesophageal reflux disease (GERD) is a prevalent chronic gastrointestinal disorder that affects a substantial proportion of the global population. It is characterized by the extensive backward flow of stomach contents into the esophagus, leading to troublesome symptoms and potential complications. Proton pump inhibitors (PPIs) have long been the cornerstone of pharmacological treatment for GERD, effectively suppressing gastric acid secretion. However, a substantial subset of patients, referred to as PPI-refractory GERD, experience inadequate symptom control despite optimal PPI therapy. GERD significantly impacts patients' quality of life, affecting domains, such as vitality, pain, and physical functioning. Consequently, there is an urgent need for alternative therapeutic strategies and novel pharmacologic agents to provide more effective, long-term relief. Emerging treatment options include potassium-competitive acid blockers (PCABs) like vonoprazan, which offer more potent and sustained inhibition of gastric acid secretion compared to traditional PPIs. Additionally, prokinetic agents such as itopride have gained attention due to their potential to improve GERD symptoms by enhancing gastrointestinal motility and accelerating gastric emptying. This article reviews the mechanisms of action, clinical efficacy, and potential of these novel therapeutic approaches in improving patient outcomes in GERD management. With the growing prevalence of PPI resistance and side effects, a personalized, multifaceted approach to treatment is becoming increasingly necessary to optimize care for patients with GERD.

Proton-pump inhibitor (PPI) use for management of gastroesophageal reflux disease (GERD) consists of a short-duration trial, according to guidelines. Long-term usage is appropriate under certain indications. Literature has increasingly documented an adverse effect profile of PPIs, including kidney disease and bone fragility.

To investigate the rate of occurrence of osteopenia, osteoporosis, and chronic kidney disease (CKD) in patients using PPI therapy for longer than the recommended trial period of 8 weeks.

Retrospective cohort analysis of a single-site primary care clinic. Patients aged 18 to 65 years with PPI prescriptions longer than 8 weeks were included. Information regarding PPI prescriptions, demographics, and medical diagnoses was collected.

The search discovered 293 PPI-users and 1908 never-PPI-users. Demographics varied, with a P-value <0.05 in age, body mass index (BMI), and black population (higher in PPI group). The PPI cohort featured higher rates of osteoporosis/osteopenia and CKD (P < 0.001). The odds ratios (ORs) of diagnosis with PPI use was 2.91 (95% CI = [1.692, 4.979]) in osteoporosis/osteopenia. The OR was 1.14 (95% CI = [1.141, 2.229]) in CKD and PPI use but higher with diabetes, elevated BMI, black race, and male gender.

We observed increased occurrence rates of osteoporosis, or osteopenia, and CKD in patients with prolonged PPI use. Demographics varied in age, BMI, and black race proportion. A logistic regression revealed increased likelihood of kidney disease and osteoporosis/osteopenia in association with PPI use. These results add to the evidence regarding long-term PPI use and the development of these conditions, but additional studies are needed.

The impact of proton pump inhibitors (PPIs) use on worsening renal function is controversial and lacks a solid pathophysiological explanation.

To assess the risk of worsening renal function and acute kidney injury (AKI) in PPI initiators as compared with H2-blockers initiators.

Retrospective cohort study using longitudinal records from BIGAN, a population-based health database of Aragón (Spain).

PPIs (n = 119,520) and H2-blockers (n = 3,086) initiators between 2015 and 2020 with preserved renal function. They were followed until the occurrence of an adverse kidney event, death, lost to follow-up or June 2021.

Primary endpoints were worsening kidney function (measured as sCr ≥ 2 times baseline, eGFR < 60 ml/min/1.73m2, a decrease in eGFR 30-50% from baseline or end stage renal disease) and AKI (measured by Aberdeen algorithm or hospitalization due to AKI). Incidence rates (IRs) per 1,000 persons-years were reported and Cox regression was used to calculate Hazard ratios (HRs), adjusted for confounders.

Crude IRs for worsening kidney function were consistently lower for ranitidine than for PPIs (eGFR < 60 ml/min/1.73m2: IR 18.7 95%CI (12.0-27.8) for ranitidine, IR 31.2 95%CI (29.9-32.5) for omeprazole). However, the risk of incident worsening function did not significantly differ in the Cox regression analysis adjusting for confounders (HR 0.99 95%CI (0.66-1.48) for omeprazole, as compared to ranitidine). PPI initiators consistently showed lower IRs of AKI using Aberdeen algorithm (IR 33.8 95%CI (32.4-35.1) for omeprazole, IR 52.8 95%CI (40.9-67.1) for ranitidine) and lower risk of AKI (HR 0.54 95%CI (0.42-0.70) for omeprazole, as compared to ranitidine).

No clinically relevant differences were observed for worsening kidney function between PPIs and H2-blockers initiators. PPIs users presented a reduced risk of AKI compared to ranitidine initiators.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based approach for strategies to diagnose and manage GERD. This document was developed using the Grading of Recommendations Assessment, Development, and Evaluation framework and serves as an update to the 2014 ASGE guideline on the role of endoscopy in the management of GERD. This updated guideline addresses the indications for endoscopy in patients with GERD as well as in the emerging population of patients who develop GERD after sleeve gastrectomy or peroral endoscopic myotomy. It also discusses how to endoscopically evaluate gastroesophageal junctional integrity in a comprehensive and uniform manner. Importantly, this guideline also discusses management strategies for GERD including the role of lifestyle interventions, proton pump inhibitors (PPIs), and endoscopic antireflux therapy (including transoral incisionless fundoplication [TIF], radiofrequency energy, and combined hiatal hernia repair and TIF [cTIF]) in the management of GERD. The ASGE suggests upper endoscopy for the evaluation of GERD in patients with alarm symptoms, with multiple risk factors for Barrett's esophagus, and with a history of sleeve gastrectomy. The ASGE recommends careful endoscopic evaluation, reporting, and photo-documentation of objective GERD findings with attention to gastroesophageal junction landmarks and integrity in patients who undergo upper endoscopy to improve care. In patients with GERD symptoms, the ASGE recommends lifestyle modifications. In patients with symptomatic and confirmed GERD with predominant heartburn symptoms, the ASGE recommends medical management including PPIs at the lowest dose for the shortest duration possible while initiating discussion about long-term management options. In patients with confirmed GERD with small hiatal hernias (≤2 cm) and Hill grade I or II who meet specific criteria, the ASGE suggests evaluation for TIF as an alternative to chronic medical management. In patients with persistent GERD with large hiatal hernias (> 2cm) and Hill grade III or IV, the ASGE suggests either cTIF or surgical therapy based on multidisciplinary review. This document summarizes the methods, analyses, and decision processes used to reach the final recommendations and represents the official ASGE recommendations on the above topics.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based approach for strategies to diagnose and manage GERD. This document was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework and serves as an update to the prior ASGE guideline on the role of endoscopy in the management of GERD (2014). The updated guideline addresses the indications for endoscopy in patients with GERD, including patients who have undergone sleeve gastrectomy (SG) and peroral endoscopic myotomy (POEM). It also discusses endoscopic evaluation of gastroesophageal junctional integrity comprehensively and uniformly. Important, this guideline discusses management strategies for GERD including lifestyle interventions, proton pump inhibitors (PPIs), and endoscopic antireflux therapy including transoral incisionless fundoplication (TIF), radiofrequency energy, and TIF combined with hiatal hernia repair (cTIF). The ASGE recommends upper endoscopy for the evaluation of GERD in patients with alarm symptoms. The ASGE suggests upper endoscopy for symptomatic patients with a history of SG and POEM. The ASGE recommends careful endoscopic evaluation, reporting, and photo-documentation of objective GERD findings and gastroesophageal junction landmarks and integrity to improve patient care and outcomes. In patients with GERD symptoms, the ASGE recommends lifestyle modifications. In patients with symptomatic and confirmed GERD with predominant heartburn symptoms, the ASGE recommends medical management including PPIs at the lowest dose for the shortest duration while initiating discussion about long-term management options. In patients with confirmed GERD with small hiatal hernia (≤2 cm) and Hill grade I or II flap valve who meet specific criteria, the ASGE suggests evaluation for TIF as an alternative to long-term medical management. In patients with confirmed GERD with a large hiatal hernia (>2 cm) and Hill grade 3 or 4 flap valve, the ASGE suggests evaluation for combined endoscopic-surgical TIF (cTIF) in a multidisciplinary review. This document clearly outlines the methodology, analysis, and decision used to reach the final recommendations and represents the official ASGE recommendations on the above topics.

Physiologically relevant gastrointestinal digestion models for infants, adults, and the elderly are commonly used to explore the fate of food in vitro. However, no consensus protocol exists to simulate the specific conditions observed in the stomach of people using oral proton pump inhibitors (PPIs), a class of widely prescribed medications that reduce gastric acid secretion and may alter food digestion and nutrient absorption. The first objective of this study was to propose an in vitro gastric digestion protocol adapted to model PPI use. This protocol is an extension of the semi-dynamic INFOGEST protocol previously developed to mimic the digestion of an adult human (referred to hereinafter as "Standard"), with two modifications based on reported clinical effects of PPIs: (i) a final gastric pH of 4.2 and (ii) a 50 % reduction in simulated gastric acid fluid volume. The second objective was to compare the release kinetics of peptides, soluble carbohydrates, lipids, and minerals during simulated gastric digestion of a mixed meal (bread, cheese, and tomato) with both standard and PPI versions of the protocol. Results demonstrated that the release of peptides, arabinose, and minerals, including calcium, magnesium, and phosphorus, was significantly (p < 0.05) reduced in the PPI model, while the hydrolyses of starch and lipids, assessed through maltose release and triacylglycerol disappearance, respectively, were not significantly affected. These findings are in agreement with the expected effects of reduced gastric acidity on pepsin activity and mineral solubility. These findings are also consistent with known or presumed side effects of PPIs such as an increased risk of hypomagnesemia, fractures, skeletal muscle loss, and vitamin B12 deficiency. In conclusion, this modified INFOGEST protocol appears to serve as a valuable tool to study the side effects of PPI use on food digestion and related nutrient bioaccessibility.

Proton pump inhibitors (PPIs) are widely used, including among cancer patients, to manage gastroesophageal reflux and other gastric acid-related disorders. Recent evidence suggests associations between long-term PPI use and higher risks for various adverse health outcomes, including greater mortality.

To investigate the association between PPI use and all-cause mortality among cancer patients by a comprehensive analysis after adjustment for various confounders and a robust methodological approach to minimize bias.

This retrospective cohort study used data from the TriNetX research network, with electronic health records from multiple healthcare organizations. The study employed a new-user, active comparator design, which compared newly treated PPI users with non-users and newly treated histamine2 receptor antagonists (H2RA) users among adult cancer patients. Newly prescribed PPIs (esomeprazole, lansoprazole, omeprazole, pantoprazole, or rabeprazole) users were compared to non-users or newly prescribed H2RAs (cimetidine, famotidine, nizatidine, or ranitidine) users. The primary outcome was all-cause mortality. Each patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence interval (CI).

During the follow-up period (median 5.4 ± 1.8 years for PPI users and 6.5 ± 1.0 years for non-users), PPI users demonstrated a higher all-cause mortality rate than non-users after 1 year, 2 years, and at the end of follow up (HRs: 2.34-2.72). Compared with H2RA users, PPI users demonstrated a higher rate of all-cause mortality HR: 1.51 (95%CI: 1.41-1.69). Similar results were observed across sensitivity analyses by excluding deaths from the first 9 months and 1-year post-exposure, confirming the robustness of these findings. In a sensitivity analysis, we analyzed all-cause mortality outcomes between former PPI users and individuals who have never used PPIs, providing insights into the long-term effects of past PPI use. In addition, at 1-year follow-up, the analysis revealed a significant difference in mortality rates between former PPI users and non-users (HR: 1.84; 95%CI: 1.82-1.96).

PPI use among cancer patients was associated with a higher risk of all-cause mortality compared to non-users or H2RA users. These findings emphasize the need for cautious use of PPIs in cancer patients and suggest that alternative treatments should be considered when clinically feasible. However, further studies are needed to corroborate our findings, given the significant adverse outcomes in cancer patients.

Gastroesophageal reflux disease (GERD) poses a substantial global health challenge, with prevalence rates exhibiting geographical variation. Despite its widespread recognition, the exact prevalence and associated risk factors remain elusive. This article comprehensively analyzed the global burden of GERD, shedding light on its risk factors, underlying pathophysiological mechanisms, current diagnostic modalities, evolving management strategies tailored to diverse patient profiles, and complex determinants contributing to treatment failures. A deeper comprehension of GERD is achieved by dissecting these intricate facets, paving the way for enhanced clinical management and improved patient outcomes.

This study was performed to evaluate the utilization patterns of acid suppressants following the withdrawal of ranitidine in Korea.

Health Insurance Review & Assessment Service (HIRA) data from January 2016 to May 2023 were utilized to assess the usage of histamine H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) for acid-related diseases. Drug utilization was calculated for each agent based on the defined daily dose (DDD). To evaluate changes in utilization following the ranitidine recall, an interrupted time series analysis was conducted using segmented linear regression and an autoregressive integrated moving average model.

Before the withdrawal of ranitidine, the DDD per 100 000 inhabitants per day was increasing by 6.9 (95% confidence interval [CI], 4.7 to 9.0) for H2RAs and by 19.3 (95% CI, 16.9 to 21.8) for PPIs each month. After the recall, H2RA utilization immediately declined by -1041.7 (95% CI, -1115.8 to -967.7), followed by a monthly increase of 6.6 (95% CI, 3.7 to 9.6) above the previous trend. PPI utilization temporarily surged by 235.2 (95% CI, 149.1 to 321.3), then displayed a monthly increase of 4.1 (95% CI, 0.7 to 7.6) on top of the pre-recall trend. Among PPIs, esomeprazole and rabeprazole demonstrated notable increases, representing the most commonly used acid suppressants in 2023.

PPI usage rose prominently following the withdrawal of ranitidine from the market. Considering the potential adverse effects of PPIs, further research is necessary to evaluate the public health implications of shifts in the utilization of acid suppressants.

Proton pump inhibitors (PPIs) are widely known drugs that are used quite frequently and indicated in both the short and long terms, in numerous acid-related diseases. Our aim was to produce an expert review that establishes recommendations for the adequate prescription and deprescription of PPIs.

A group of experts in PPI use that are members of the Asociación Mexicana de Gastroenterología (AMG), after extensively reviewing the published literature and discussing each recommendation at a face-to-face meeting, prepared the present document of good clinical practice recommendations. This document is not intended to be a clinical practice guideline or utilize the methodology said format requires.

Eighteen experts on PPI use developed 22 good clinical practice recommendations for prescribing short-term, long-term, and on-demand PPIs, recognizing adverse events, and lastly, deprescribing PPIs, in acid-related diseases.

At present, there is scientific evidence on PPI use in numerous diseases, some in the short term (4-8 weeks), others on-demand (for short periods until symptoms improve), or in the long term (without suspending). Numerous adverse effects have been attributed to PPIs, but the majority have no well-established causal association. Nevertheless, PPIs should be suspended when there is no clear indication for their use. These recommendations aim to aid general physicians and specialists, with respect to PPI prescription and deprescription.

Proton pump inhibitors (PPIs) are among the most widely used drugs worldwide. However, their influence on the progression of end-stage kidney disease (ESKD) in established chronic kidney disease (CKD) cases is unclear. Using the Korean Health Insurance Review and Assessment database encoded by the Observational Medical Outcomes Partnership-Common Data Model (OMOP-CDM), patients with stage 3 or 4 CKD initiating PPIs or histamine-2 receptor antagonists (H2RAs) for over 90 days were enrolled from 2012 through 2021. Incidence of ESKD events between the groups were compared using a cox proportional hazard model. A total of 34,656 eligible patients were included. Of the patients, 65.1% had CKD stage 3, 44.5% aged > 75 years, 59.8% were male individuals, and 68.3% had diabetes. After 1:1 propensity score matching, ESKD progression was observed in 2327 out of 19,438 patients and it was more frequent in PPI users (incidence rate, 10.5/100PYs) than that in H2RA users (incidence rate, 9.2/100PYs; IRR, 1.14 [1.07-1.12]). Using the subgroup analysis, IRR was significantly higher in patients with CKD stage 3 (IRR 1.40 [1.21-1.60]), whereas it was not in those with CKD stage 4 (IRR 1.04 [0.94-1.15]). A similar trend was observed in patients with CKD 3 or 4 with and without diabetes. In general, PPI use is associated with a 14% higher risk of ESKD progression in patients with CKD stage 3 or 4. However, the influence of PPIs differed according to the comorbidities and risks of adverse kidney outcomes.

Although Proton pump inhibitors (PPIs) were mostly prescribed for gastrointestinal (GI) disease widely, there were numerous studies about PPIs and adverse renal outcome. Most evidence was to evaluate the risk of PPIs in patients with normal renal function and in the absence of the moderate to advanced chronic kidney disease (CKD). This study focuses on the accelerated progression of renal function following proton pump inhibitors (PPIs) use, and the increased risks of acute kidney injury (AKI) among moderate to advanced CKD (pre-ESRD) patients.

A retrospective cohort study was conducted by including adult patients with chronic kidney disease (CKD) stages 3b to 5 who initiated PPI or H2 blocker (H2B) therapy between 2011 and 2018. The risk of renal events was assessed using the Cox proportional hazard model to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). Sensitivity analyses were performed, including propensity score matching, as-treated analysis, and subgroup analysis.

The cohort comprised 83,432 pre-ESRD patients, with 5,138 treated with H2B and 1,051 with PPIs. The progression to ESRD was significantly more likely in patients using PPIs compared to those using H2B (adjusted HR, 1.495; 95% CI: 1.198-1.867). Specifically, omeprazole (adjusted HR, 1.784; 95% CI: 1.079-2.951) and esomeprazole (adjusted HR, 1.847; 95% CI: 1.332-2.561) were associated with a notably higher risk of ESRD and AKI.

The study highlights the significance of the accelerated renal risk, especially for moderate to advanced CKD patients, when prescribing PPIs and to implicate the clinicians prescribed PPIs and H2B in pre-ESRD patients.

Patients with chronic kidney disease (CKD) are at high risk for bone fractures, which are associated with high morbidity and mortality. Proton pump inhibitors (PPI) have been linked to an increased risk for fractures in the general population as well as in patients with need for hemodialysis, but studies in patients with CKD are currently missing.

We performed a population-based observational case-control study exploring a sample of patients with CKD derived from the IQVIATM Disease Analyzer database. Patients with and without fractures were matched using the 1:1 nearest neighbor propensity score matching method. To investigate the association between PPI use and fractures, multivariable logistic regression analyses were performed adjusting for confounding factors.

In total, 6076 patients with and 6076 patients without fractures were matched and subsequently available for analyses. In the total cohort, PPI use was associated with an increased risk for fractures [odds ratio (OR) 1.68; 95% confidence interval (95% CI) 1.55-1.83]. This association was noted for nearly all types of fractures. The strongest association between PPI use and fractures was found in patients below the age of 60 years with a PPI prescription for longer than 2 years (OR 6.85; 95% CI 1.85-25.38). The same was true when analyzing cumulative PPI doses. Here, patients below the age of 60 years with a cumulative PPI dose above 16 000 mg (highest quartile) had the highest risk for fractures (OR 4.62; 95% CI 1.87-11.44). There was no difference between men or women regarding the association between PPI use and fractures.

This study provides evidence that PPI use is associated with fractures in patients with CKD. Deprescription of PPI in patients without an indication for treatment could be a modifiable risk factor to reduce fracture risk in this high-risk group.

Proton pump inhibitors (PPIs) are effective treatments for acid-related disorders but may pose tumor risks with long-term use. Current research on PPI-associated tumor adverse events (TAEs) is limited and inconclusive. This study aims to comprehensively analyze the relationship between PPIs and TAEs.

We analyzed PPI adverse reaction reports from the FDA Adverse Event Reporting System (FAERS) database spanning from 2004 to 2024, focusing on five commonly used PPIs: esomeprazole, pantoprazole, lansoprazole, omeprazole, and rabeprazole. We conducted a disproportionality analysis utilizing the Reporting Odds Ratio (ROR) to identify potential TAEs associated with PPIs. We conducted univariate logistic regression analysis to explore the influencing factors.

A total of 3,133 TAEs were identified, representing 2.36% of all PPI-related adverse events (AEs). The most common TAEs were gastric cancer (19.05%) and malignant neoplasm (7.23%). Disproportionality analysis revealed ten significant TAEs associated with PPIs, including gastric adenocarcinoma and renal cell carcinoma. The median age of those reporting TAEs was 59 (interquartile range [IQR]: 51-70), and 29.70% of them resulted in a fatality. TAEs associated with PPIs were less likely to occur in elderly patients (65-75: OR = 0.91 [0.87-0.95], p < 0.001; >75: OR = 0.93 [0.89-0.98], p < 0.01).

TAEs constitute a small but significant fraction of PPI-related AEs. This study highlights the need for cautious long-term use of PPIs and further research to understand the underlying mechanisms and risk factors. Clinicians should be aware of the potential tumor risks associated with prolonged PPI treatment.

Gastroesophageal reflux disease (GERD) is a common medical condition presenting with heartburn, regurgitation, cough, hoarseness, and/or wheezing. Patients with classic GERD symptoms often do not require diagnostic studies before empirical treatment is initiated. However, if atypical features are present, including alarm symptoms for malignancy, or if symptoms do not respond to conventional treatment, upper endoscopy may be necessary. The optimal management of GERD, which is the subject of debate, depends on the frequency and severity of symptoms. In 2021, the American College of Gastroenterology published updated recommendations for diagnosis and management of GERD. In addition to histamine-2 receptor antagonist or proton-pump inhibitor therapy, which may be prescribed as needed or continuously, lifestyle and dietary modification are often advised. Here, 2 physicians, a primary care practitioner and a gastroenterologist, debate how to manage a patient with GERD symptoms. They discuss the diagnosis of this condition, its initial management, indications for upper endoscopy, and how to care for the patient whose condition does not respond to empirical therapy.

The use of proton-pump inhibitors (PPI) is linked with infrequent but serious adverse events, including acute kidney injury, chronic kidney disease (CKD) and progression of CKD. Data on renal safety in routine use of PPI are more relevant to clinical practice. We studied whether such use of PPI is associated with renal dysfunction.

Patients taking PPI for at least six weeks had serum creatinine tested pre (n = 200) and post (n = 180) recruitment. These patients were then advised to follow-up: those taking PPI for at least 90 days in the next six months (n = 77) and at least another 90 days in the following six months (n = 50), had serum creatinine tested at such follow-up. Renal dysfunction was defined as any increase in serum creatinine level above baseline.

The 200 patients recruited had mean age 39.6 (SD 9.2) years. Ninety-eight (49%) patients had a history of previous PPI use (median six months; interquartile range [IQR] 3-24). Only 20 (11.1%) patients at six weeks, 11 (14.3%) at six months and six (12%) at one year had increase in creatinine level; a majority of them had less than 0.3 mg/dL increase. Ten of these 20 (six weeks), five of 11 (six months) and five of six (one year) had other risk factors for renal dysfunction. No patient developed CKD during the study period.

Mild and non-progressive increase in serum creatinine occurred in 10% to 15% of patients on routine PPI use. A majority of them had other risk factors. Small sample size and short follow-up duration are a few limitations of this study.

To investigate the association between the use of proton pump inhibitors (PPIs) and overactive bladder (OAB) in adults.

This study adopts a cross-sectional approach to scrutinize data derived from the National Health and Nutrition Examination Survey (NHANES), spanning from 2007 to 2018. It employs multivariable logistic regression along with restricted cubic splines (RCS) to investigate the relationship between the use of PPI and the incidence of OAB. Additionally, through interaction and stratification analyses, the study delves into how specific factors may influence this correlation.

A total of 24,458 adults participated in this study. Individuals using PPIs exhibited higher rates of nocturia, urge incontinence, and OAB compared to non-users. After full adjustment, PPI users had a significantly increased risk of developing OAB (OR=1.36, 95%CI: 1.17-1.60). Moreover, with each year of continued PPI usage, the frequency of OAB symptoms escalated by 3% (P = .01). Further examinations within various subgroups maintained a uniform direction in these effect estimates.

The findings of this research highlight a noteworthy positive link between the use of PPIs and the emergence of OAB among adults. Moreover, it was observed that an extended period of using PPIs correlates with a heightened likelihood of encountering OAB.

Dual-antiplatelet therapy (DAPT) and proton pump inhibitor (PPI) are frequently prescribed after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) placement. However, studies that evaluate the optimal PPI when used as primary prevention in patients without a history of peptic ulcer disease or upper gastrointestinal bleeding (UGIB), particularly in the context of DAPT involving prasugrel, are lacking. This study aimed to assess the efficacy and safety of PPI use in preventing UGIB in this patient population.

This study included patients who underwent PCI with coronary stent placement for acute coronary syndrome or stable angina at our institution from January 2015 to December 2020. Eligible patients started DAPT with aspirin and prasugrel and concomitantly received PPI therapy (lansoprazole or esomeprazole), with a follow-up period of two years. The primary endpoint was UGIB incidence, diagnosed during follow-up, serving as an efficacy measure. Secondary endpoints included the assessment of major bleeding (as defined by the Thrombolysis in Myocardial Infarction major bleeding criteria) and clinically relevant non-major bleeding events. Safety outcomes focused on adverse event incidence attributable to PPI use.

Among the 165 patients analyzed, 109 and 56 were included in the lansoprazole and esomeprazole groups, respectively, with cumulative incidence of UGIB at 96 weeks of 0.9% (1/109) and 3.6% (2/56). No significant differences in terms of major bleeding events or other bleeding outcomes were observed between the two groups. Adverse events related to PPI use were reported as diarrhea/soft stools in 7 (6%) cases and thrombocytopenia in 1 (1%) case in the lansoprazole group, whereas no such events were observed in the esomeprazole group. No clinically significant hematologic or biochemical abnormalities were reported.

This study evaluated the efficacy and safety of PPIs in combination with DAPT, including prasugrel, following PCI, and suggests that lansoprazole and esomeprazole may offer comparable efficacy in preventing UGIB.

Lupus nephritis is a common complication of systemic lupus erythematosus (SLE) and a determinant of overall morbidity and mortality, as lupus nephritis-related chronic kidney disease (CKD) drives cardiovascular disease and secondary immunodeficiency. Two lines of action are required to prevent the progression of lupus nephritis-related CKD: suppression of autoimmune SLE activity, which is a risk factor for immunopathology-related irreversible kidney injury, and management of non-immune risk factors that contribute to CKD progression. As each episode or relapse of active lupus nephritis implicates CKD progression, preventing flares of lupus nephritis is a key treatment target. Non-immune risk factors of CKD mostly include causes of nephron hyperfiltration, such as obesity, hypertension, sodium- or protein-rich diets and type 2 diabetes mellitus, as well as pregnancy. Nephrotoxic agents and smoking also drive kidney cell loss. Intrinsic risk factors for CKD progression include poor nephron endowment because of prematurity at birth, nephropathic genetic variants, ageing, male sex and previous or concomitant kidney diseases. Care for lupus nephritis involves the control of all modifiable risk factors of CKD progression. In addition, remnant nephron overload can be reduced using early dual therapy with inhibitors of the renin-angiotensin system and sodium-glucose transporter-2, whereas further renoprotective drug interventions are underway. As patients with lupus nephritis are at risk of CKD progression, they would all benefit from interdisciplinary care to minimize the risk of kidney failure, cardiovascular disease and infections.

Gastroesophageal reflux disease (GERD) significantly affects the health-related quality of life and healthcare costs. The prevalence of this disease is increasing in Asia, leading to a rapid increase in the demand of proton pump inhibitors (PPIs). Despite effective symptom management during initial treatment, relapse rates after PPI cessation remain high in patients with GERD, warranting longterm maintenance therapy. Concerns regarding potential side effects related to the long-term use of PPIs are escalating with increased usage. Studies have reported diverse side effects of PPIs, such as increased fracture risk, cardiovascular concerns, enteric infections, neurological diseases, and potential associations with gastric cancer. However, definitive causal relationships remain unclear. This review comprehensively summarizes the latest knowledge on the potential risks associated with long-term use of PPIs. Continuous or noncontinuous therapy can be used as a maintenance treatment modality for GERD. For patients with mild GERD, including those with nonerosive and mildly erosive reflux disease, on-demand therapy following a sufficient period of continuous maintenance therapy is recommended as a long-term maintenance treatment option.

Background/Objectives: Proton pump inhibitors (PPIs) are amongst the most commonly prescribed classes of medication. However, inappropriate PPI use can lead to several adverse drug reactions (ADRs). Limited data exist on factors contributing to the risk of ADRs associated with PPI prescribing patterns in the Eastern Region of Saudi Arabia. This retrospective, cross-sectional study aimed to assess the prevalence and the pattern of PPI use and to identify factors contributing to the risk of ADRs. Methods: Data were collected from electronic medical records of patients at Al-Qateef Central Hospital from January 2020 to December 2021. The inclusion criteria included patients aged ≥40 years attending an outpatient medical care clinic. PPI prescribing patterns were categorized based on their dosage intensity into low-dose, medium-dose (MD), and high-dose (HD) categories. Binary and multinominal logistic regression models were used to determine the relationship between PPI prescribing patterns and use, categorized by MD or HD, and patient characteristics, adjusted for significant covariates. Results are presented as adjusted odds ratio (OR) with corresponding 95% confidence intervals (95% CI). Results: The study included 41,084 patients. The prevalence of PPI prescribing was 31%. PPI users were more frequently found to be females than males (52% vs. 50%, p = 0.013); they were also likely to be prescribed more medications (7 vs. 6, p < 0.001), but less likely to have gastritis-related diseases (34% vs. 32%, p < 0.001) compared to non-users. PPI HD users were more likely male (56% vs. 43%, p < 0.001), older (53 vs. 52 years, p < 0.001), and prescribed more medications (11.8 vs. 2.8, p < 0.001) compared to MD users. PPI usage was associated with concurrent use of antiplatelet drugs (OR = 1.08, 95% CI 1.01-1.15). An increasing number of prescribed medications was associated with HD usage (OR = 1.13, 95% CI 1.12-1.14), but negatively associated with MD usage (OR = 0.7 95% CI 0.69-0.71). Female gender was negatively associated with HD usage (OR = 0.85, 95% CI 0.79-0.91). Conclusions: Our findings indicate that 31% of the included cohort were prescribed PPI. Inappropriate PPI prescribing related to the drug's omission is a concern as PPI non-users presented with valid indications such as gastritis. Male gender and increasing NPM were the common factors contributing to increased risk of PPI ADR. This study points to the importance of re-evaluating PPI use to ensure effective therapy with minimum risks of ADR.

Proton pump inhibitors (PPIs) are one of the most commonly prescribed medications. However, PPI usage is linked to a higher risk of both acute and chronic renal damage by mechanisms not entirely known. The present study demonstrates that omeprazole (10 mg/kg body weight, i.p.) causes TGF-β/Smad signaling activation and subsequent expression of the profibrotic genes CTGF and TIMP-1 in rat kidney. Increased production of CTGF and TIMP-1 accompany activation of the TGF-β/Smad signaling cascade. However, simultaneous treatment of omeprazole and the TGF-β inhibitor, disitertide (P144) (1 mg/kg body weight i.p.) suppresses the TGF-β/Smad signaling pathway and subsequent production of CTGF and TIMP-1. Additionally, TGF-β level in rat kidney was highly reduced in animals treated with the ROS (reactive oxygen species) scavenger, N-acetyl cysteine (NAC) (100 mg/kg body weight i.p.) before omeprazole administration. Furthermore, the reduction in SOD activity brought by omeprazole was returned to the normal level in those animals. However, MDA level increased by omeprazole was highly reduced in the presence of NAC. Collectively, the current findings demonstrate that omeprazole has the ability to promote the expression of the profibrotic genes CTGF and TIMP-1 in a ROS and TGF-β dependent manner. The present study suggests the co-use of ROS scavenger to improve the therapeutic use of the PPI omeprazole.

Proton pump inhibitors (PPIs) are widely used for acid-related gastrointestinal disorders; however, concerns have arisen about their prolonged and inappropriate use. Although generally considered safe, recent evidence has linked PPI use with an increased risk of kidney disease, stomach cancer, pneumonia, dementia, cardiovascular events and potential bone health problems. This systematic review examines the effects of PPIs on bone health, including osteoporosis and changes in phosphocalcic and magnesium metabolism, through a comprehensive analysis of the recent literature. The relationship between PPIs, bone mineral density and fracture risk, especially in populations with comorbidities, is complex and we propose a focus based on recent data. Studies of the effect of PPI use on bone mineral density have shown mixed results and require further investigation. Observational studies have indicated an increased risk of fractures, particularly vertebral fractures, associated with PPI use. Recent meta-analyses have confirmed an association between PPI use and hip fractures with a dose-dependent effect. More recently, PPIs have been associated with serious disturbances in phosphocalcic and magnesium metabolism that require careful management and discontinuation. Proton pump inhibitor-induced hypomagnesemia (PPIH) is a well-established phenomenon. In addition, hypocalcemia secondary to severe hypomagnesemia has been described. Despite growing evidence of PPI-related risks, further research is essential to better understand the complex mechanisms, as most data are from observational studies and do not establish a causal relationship. This review emphasizes the need for judicious prescription practices, particularly in long-term use scenarios and rheumatological contexts.

Despite reliable evidence of adverse drug effects, the substantially increased prescription rates of proton pump inhibitors (PPIs) remain at a high level. This study analyzed the appropriateness of PPI prescriptions among residents of nursing homes in three regions of Germany. Baseline data of a cluster-randomized controlled trial were used to determine the prevalence of PPI prescriptions, the validity of indications, and the adequacy of the prescribed dosages according to 1. their drug approvals and 2. valid recommendation guidelines. Regression analyses were conducted to assess associated factors. A total of 437 residents in 37 nursing homes were included (mean age 83 ± 9.2 years, 72% women). The PPI prescription prevalence was 44% (n = 193). In 52/193 (27%) there was no adequate indication, and in 54 (39%) of 138 indicated PPI prescriptions it was overdosed. Yet, in only less than one-third (28%) of "adequate" prescriptions, the indication was according to the PPI approvals, whereas the majority (72%) were off-label indications in line with valid guideline recommendations. Non-indicated PPI prescription was associated with the total number of prescribed drugs (OR 1.32; 95% CI 1.18-1.62; p = 0.013). There were no associations with age, level of care dependency, cognitive impairment, prescription of psychotropic drugs, number of chronic diseases, number of physicians' consultations, or study region. To conclude, in 55%, the high prescription prevalence among residents was either not indicated or overdosed. In total, only 20% (39/193) of cases of PPI use complied with the approved indications. There is a need for quality control of 1. PPI administration in German nursing homes, and 2. of guideline recommendations expanding the off-label PPI use by 72% within the indication scale, predominantly from wide prescription for low-dose ASA.

With the rapid expansion in the development and clinical utility of immune checkpoint inhibitors (ICIs) for oncology, the continual evaluation of the safety profile of such agents is imperative. The safety profile of ICIs as monotherapy is dominated by immune-related adverse events, which can be considered as an extension of the mechanism of action of these immunomodulatory drugs. Further to this, an emerging theme is that ICI treatment can significantly impact upon the tolerability of coadministered medications. Numerous reports in literature indicate that ICIs may alter the immunological perception of coadministered drugs, resulting in undesirable reactions to a variety of concomitant medications. These reactions can be severe in manifestation, including hepatotoxicity and Stevens-Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN), but may also have detrimental impact on malignancy control. To minimize the impact of such drug-drug interactions on patients, it is imperative to identify medications that may cause these reactions, understand the underlying mechanisms, consider the timing and dosing of comedication, and explore alternative medications with comparable efficacies. Improving our understanding of how concomitant medications affect the safety and efficacy of ICIs can allow for potential culprit drugs to be identified/removed/desensitized. This approach will allow the continuation of ICI therapy that may have been discontinued otherwise, thereby improving malignant control and patient and drug development outcomes.

Most patients undergoing anti-reflux surgery (ARS) have a history of preoperative proton pump inhibitor (PPI) use. It is well-established that ARS is effective in restoring the anti-reflux barrier, eliminating the ongoing need for costly PPIs. Current literature lacks objective evidence supporting an optimal postoperative PPI cessation or weaning strategy, leading to wide practice variations. We sought to objectively gauge current practice and opinion surrounding the postoperative management of PPIs among expert foregut surgeons and gastroenterologists in the United States.

We created a survey of postoperative PPI management protocols, with an emphasis on discontinuation and timing of PPI cessation, and aimed to determine what factors played a role in the decision-making. An electronic survey tool (Qualtrics XM, Qualtrics, Provo, UT) was used to distribute the survey and to record the responses anonymously for a period of three months.

The survey was viewed 2658 times by 373 institutions and shared with 644 members. In total, 121 respondents participated in the survey and 111 were surgeons (92%). Fifty respondents (42%) always discontinue PPIs immediately after ARS. Of the remaining 70 respondents (58%), 46% always wean or taper PPIs postoperatively and 47% wean or taper them selectively. The majority (92%) of practitioners taper within a 3-month period postoperatively. Five respondents never discontinue PPIs after ARS. Overall, only 23 respondents (19%) stated their protocol is based on medical literature or evidence-based medicine. Instead, decision-making is primarily based on anecdotal evidence/personal preference (42%, n = 50) or prior training/mentors (39%, n = 47).

There are two major protocols used for PPI discontinuation after ARS: Nearly half of providers abruptly stop PPIs, while just over half gradually tapers them, most often in the early postoperative period. These decisions are primarily driven by institutional practices and personal preferences, underscoring the need for evidence-based recommendations.

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  ≥ 90 days. 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  ≥ 90 days may hasten eGFR decline compared to H2RA use, especially in patients with eGFR  ≥ 90 or age  < 65.

Background: Heightened scrutiny surrounds the inappropriate use of proton pump inhibitors (PPIs) due to concerns regarding potential serious adverse effects (AEs). Understanding the impact of these AEs on real-world practice is crucial. This study aimed to assess physicians' perceptions, experiences, awareness, and beliefs regarding published data on potential AEs associated with PPIs. Additionally, it sought to determine alterations in PPI prescribing patterns resulting from these AEs, explore attitudes towards PPI use, and ascertain recommendations for PPI use in clinical scenarios with varying levels of risk for upper gastrointestinal bleeding (UGIB). Method: A quantitative, cross-sectional study utilized a self-administered questionnaire, inviting 282 physicians from 55 primary healthcare centers and 334 internal medicine physicians from seven governmental hospitals to participate. Results: With a response rate of 87.8% (541/616), 74% (95% CI: 70.2-77.7) of respondents were somewhat or very familiar with published data on PPI AEs. Among the familiar, 69.5% (CI: 65.2-73.5) had somewhat or very much changed their PPI prescribing patterns. General concerns about AEs when prescribing PPIs were reported by 62% (CI: 56.7-65.1). Respondents displayed awareness of a median (IQR) of 15 (9) different AEs associated with long-term PPI use, including osteoporosis or osteopenia (90.2%), hypomagnesemia (81.5%), vitamin B12 deficiency (80.6%), and bone fracture (80.0%). Respondents believed that PPIs elevate the risk for a median (IQR) of 7 (6) different AEs, with osteoporosis or osteopenia (81.8%) being the most common, followed by hypomagnesemia (67.1%), and vitamin B12 deficiency (62.3%). The most common strategies for PPI de-escalation were PPI discontinuation (61%) and using PPI on-demand/as-needed (57.9%). The majority (87.4%) agreed or strongly agreed that PPI overuse is prevalent in Kuwait and 78.2% emphasized the necessity for large-scale education on rational PPI use for medical staff and the public. In the UGIB prevention scenarios, 43.6% recommended appropriately the PPI discontinuation in the minimal-risk scenario, while 56% recommended appropriately the PPI continuation in the high-risk scenario. Associations and comparative analyses revealed predictors influencing physicians' practices and attitudes toward PPI usage. Conclusion: These findings lay the foundation for future research and targeted interventions aimed at optimizing PPI prescribing practices and ensuring patient safety.

Proton pump inhibitors (PPIs) are among the most commonly prescribed medications. Recently, PPI use has been linked to the development of chronic kidney disease (CKD) and cardiovascular events. Our study aimed to investigate the relationship between PPI use and the incidence of chronic kidney disease using a systematic review and meta-analysis.

We performed a comprehensive literature search in PubMed, Embase, and Cochrane databases from their inception until March 2024 for relevant studies. We compared outcomes between patients using PPIs, those not using PPIs, and those using histamine-2 receptor antagonists (H2RAs). Endpoints were pooled using the DerSimonian-and-Laird random-effects model as the hazard ratio (HR) with 95% confidence intervals (CIs).

Our analysis included twelve studies with a total of 700,125 participants (286,488 on PPIs, 373,848 not on PPIs, and 39,789 on H2RAs), with follow-up periods ranging from three months to 14 years. The current meta-analysis revealed that PPI use is associated with a statistically significant increased risk of incident CKD (HR: 1.26, 95% CI: 1.16-1.38, p < 0.001) compared with non-users. Moreover, the risk of incident CKD is significantly higher in patients with PPI use compared to H2RA use (HR: 1.34, 95% CI: 1.13-1.59, p < 0.001). The results remained unchanged in terms of magnitude and direction after a leave-one-out analysis for both outcomes.

Our multifaceted analysis showed that PPI use was associated with a higher incidence of CKD when compared to non-PPI use and H2RA use, respectively. These findings advocate for heightened vigilance and judicious use of long-term PPIs. Further large prospective longitudinal studies are warranted to validate these observations.

Chronic kidney disease (CKD) is an insidious disease that requires early nephroprotective measures to delay progression to end-stage kidney disease. The objective of this study was to describe the management of patients with CKD in primary care, including clinical and biological monitoring and prescribed treatments. A retrospective, single-centre study was conducted on adult patients who were treated in the Maison de Neufchâtel (France) between 2012 and 2017 at least once a year. The inclusion criteria were 2 estimated glomerular filtration rate (eGFR) measurements <60 mL/min more than 3 months apart. Two subgroups were constituted according to whether CKD was coded in the electronic medical records (EMRs).

A total of 291 (6.7%, CI95% 5.9-7.4) patients with CKD were included. The mean eGFR was 51.0 ± 16.4 mL/min. Hypertension was the most frequent health problem reported (n = 93, 32%). Nephrotective agents were prescribed in 194 (66.7%) patients, non-steroidal anti-inflammatory drugs (NSAIDs) in 22 (8%) patients, and proton-pump inhibitors (PPIs) in 147 (47%) patients. CKD coding in EMRs was associated with dosage of natraemia (n = 34, 100%, P < 0.01), albuminuria (n = 20, 58%, P < 0.01), vitamin D (n = 14, 41%, P < 0.001), and phosphorus (n = 11, 32%, P < 0.001). Eighty-one patients (31.5%) with low eGFR without an entered code for CKD were prescribed an albuminuria dosage. Clinical monitoring could not be analysed due to poor coding.

This pilot study reinforces the hypothesis that CKD is underscreened and undermanaged. More systematic coding of medical information in EMRs and further studies on medical centre databases should improve primary care practices.

Although adverse events of proton pump inhibitors (PPIs) have been reported, there are few studies on physicians' perceptions. We aimed to investigate physicians' awareness of PPI-related adverse events and changes in treatment patterns according to their practice. We conducted an online survey of physicians using a 15-item questionnaire. The survey queried respondents' demographic information, PPI prescription patterns, perceptions, and concerns on the reported PPI-related adverse events. Concerns regarding the adverse events of PPI were assessed by dividing them into possibilities and medical causality. Of the 450 respondents, 430 were specialists, and 232 were gastroenterologists. A total of 87.8% of the respondents were generally or well aware of the adverse effects of PPI, 29.1% considered side effects when prescribing PPI, and 14.6% explained them to patients. Specialists were more aware of the side effects of PPI than general practitioners (p = 0.005), and gastroenterologists were more aware of the side effects of PPI than non-gastroenterologists (p < 0.001). However, gastroenterologists explained less to patients (p = 0.001) and preferred to reduce the dose of PPI rather than discontinue it. The adverse events that were recognized as having the highest probability of occurrence and strongest association with PPI use were bone diseases, Clostridium difficile infection, gastrointestinal infection, pneumonia, and interactions with anti-thrombotic drugs. Physicians' awareness of PPI-related adverse events and treatment patterns differed significantly according to their positions and practice. Although a number of adverse events of PPIs were reported, physicians seem to accept their significance differently according to their specialty and practice patterns.

Chronic kidney disease (CKD) is the 16th leading cause of mortality worldwide. Clinical studies have raised that long-term use of omeprazole (OME) is associated with the morbidity of CKD. OME is commonly used in clinical practice to treat peptic ulcers and gastroesophageal reflux disease. However, the mechanism underlying renal failure following OME treatment remains mostly unknown and the rodent model of OME-induced CKD is yet to be established. We described the process of renal injury after exposure to OME in mice; the early renal injury markers were increased in renal tubular epithelial cells (RTECs). And after long-term OME treatment, the OME-induced CKD mice model was established. Herein, aryl hydrocarbon receptor (AHR) translocation appeared after exposure to OME in HK-2 cells. Then for both in vivo and in vitro, we found that Ahr-knockout (KO) and AHR small interfering RNA (siRNA) substantially alleviated the OME-induced renal function impairment and tubular cell damage. Furthermore, our data demonstrate that antagonists of AHR and CYP1A1 could attenuate OME-induced tubular cell impairment in HK-2 cells. Taken together, these data indicate that OME induces CKD through the activation of the AHR-CYP axis in RTECs. Our findings suggest that blocking the AHR-CYP1A1 pathway acts as a potential strategy for the treatment of CKD caused by OME. KEY MESSAGES: We provide an omeprazole-induced chronic kidney disease (CKD) mice model. AHR activation and translocation process was involved in renal tubular damage and promoted the occurrence of CKD. The process of omeprazole nephrotoxicity can be ameliorated by blockade of the AHR-CYP1A1 axis.

Recent research has increasingly demonstrated an association between proton pump inhibitors (PPIs) and serious adverse events. This study aimed to evaluate the association between PPI and rhabdomyolysis (RM), examining its time-to-onset profiles using the Japanese Adverse Drug Event Report (JADER) database.

Data spanning from April 2004 to March 2022 were used. The association between PPIs and RM was evaluated using the reporting odds ratio (ROR), adjusted for sex and age. Subsequent analyses were conducted after excluding cases involving concomitant use of statins or fibrates. Furthermore, the onset time of RM and Weibull distribution parameters were calculated to evaluate the expression profile of RM, and the outcomes were examined.

RM was associated with the use of esomeprazole, omeprazole, and rabeprazole, even in the absence of concomitant statin or fibrate use. The median time to RM onset varied among PPIs, ranging from 6.5 to 127 d. The Weibull distribution parameters indicated that the hazard types of nearly all orally administered PPIs were classified as early failure or close to random failure. Regarding outcomes, cases of death were reported for all PPIs except vonoprazan.

The findings suggest the need for vigilant monitoring of RM during PPI administration, particularly in the early stages, considering the varying onset times.

Proton pump inhibitors (PPIs) are commonly prescribed medications for dyspepsia and gastroesophageal reflux. There are concerns about their use in the development of chronic kidney disease (CKD).

The available published literature fails to support an association with PPI and the development of CKD. Placebo-controlled trials demonstrate no difference in the incidence of CKD between placebo and PPI. If one examines the data according to the Bradford Hill perspective incorporating temporal relationship, the strength of association, dose-response relationship, replacement of findings, cessation of exposure, specificity of the association, and consistency with other knowledge, one can only conclude that there is no consistent relationship between PPI use and the development of CKD, or its progression.

There is insufficient evidence to link PPI exposure with the development or progression of CKD.

To determine how a large scale, multicomponent, pharmacy based intervention to reduce proton pump inhibitor (PPI) overuse affected prescribing patterns, healthcare utilization, and clinical outcomes.

Difference-in-difference study.

US Veterans Affairs Healthcare System, in which one regional network implemented the overuse intervention and all 17 others served as controls.

All individuals receiving primary care from 2009 to 2019.

Limits on PPI refills for patients without a documented indication for long term use, voiding of PPI prescriptions not recently filled, facilitated electronic prescribing of H2 receptor antagonists, and education for patients and clinicians.

The primary outcome was the percentage of patients who filled a PPI prescription per 6 months. Secondary outcomes included percentage of days PPI gastroprotection was prescribed in patients at high risk for upper gastrointestinal bleeding, percentage of patients who filled either a PPI or H2 receptor antagonist prescription, hospital admission for acid peptic disease in older adults appropriate for PPI gastroprotection, primary care visits for an upper gastrointestinal diagnosis, upper endoscopies, and PPI associated clinical conditions.

The number of patients analyzed per interval ranged from 192 607 to 250 349 in intervention sites and from 3 775 953 to 4 360 868 in control sites, with 26% of patients receiving PPIs before the intervention. The intervention was associated with an absolute reduction of 7.3% (95% confidence interval -7.6% to -7.0%) in patients who filled PPI prescriptions, an absolute reduction of 11.3% (-12.0% to -10.5%) in PPI use among patients appropriate for gastroprotection, and an absolute reduction of 5.72% (-6.08% to -5.36%) in patients who filled a PPI or H2 receptor antagonist prescription. No increases were seen in primary care visits for upper gastrointestinal diagnoses, upper endoscopies, or hospital admissions for acid peptic disease in older patients appropriate for gastroprotection. No clinically significant changes were seen in any PPI associated clinical conditions.

The multicomponent intervention was associated with reduced PPI use overall but also in patients appropriate for gastroprotection, with minimal evidence of either clinical benefits or harms.

Severe acute respiratory syndrome coronavirus 2 is a viral respiratory infection that can cause systemic disorders and lead to death, particularly in older people. Proton pump inhibitors (PPIs) increase the risk of enteric and lung infections. Considering the broad use of PPIs in older people, the potential role of PPIs in COVID-19 could be of dramatic significance. The objective of our study was to evaluate the link between PPIs and severe COVID-19 in older people.

We performed a retrospective cohort study, including all patients aged ≥65, hospitalised for a diagnosis of COVID-19. Epidemiological, clinical and biological data were extracted and we performed an Inverse Probability of Treatment Weighing method based on a propensity score.

From March 2020 to February 2021, a total of 834 patients were included, with a median age of 83 and 52.8% were male. A total of 410 patients had a PPIs prescription, 358 (87.3%) were long-term PPIs-users and 52 (12.7%) were recent PPIs-users. Among PPIs-users, 163 (39.8%) patients developed severe COVID-19 versus 113 (26.7%) in PPIs-non users (odds ratio (OR) = 1.59 [1.18-2.14]; P < 0.05). Moreover, the double dose PPI-users had a higher risk of developing severe COVID-19 (OR = 3.36 [1.17-9.66]; P < 0.05) than the full dose PPI-users (OR = 2.15 [1.22-3.76]; P < 0.05) and the half dose PPI-users (OR = 1.64 [1.13-2.37]; P < 0.05).

Our study reports evidence that the use of PPIs was associated with an increased risk of severe COVID-19 in older people.