Use Of Proton Pump Inhibitors Research Articles

Potential Risks Associated With Long-term Use of Proton Pump Inhibitors and the Maintenance Treatment Modality for Patients With Mild Gastroesophageal Reflux Disease.

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.

Deprescribing strategies for proton pump inhibitors.

Proton pump inhibitors (PPIs) are widely used for a number of gastric-acid related diseases. Although these agents demonstrate enhanced efficacy and tolerability compared with other acid-suppressive therapies, long-term use is associated with a number of adverse reactions. This article summarizes appropriate indications for short- and long-term use of PPIs and describes deprescribing strategies that clinicians can use to reduce unnecessary PPI use in their patients.

Association between reduced risk of gastrointestinal bleeding related to proton pump inhibitor use and subsequent all-cause death in patients with percutaneous coronary intervention

Abstract Background Gastrointestinal bleeding is the leading cause of post-percutaneous coronary intervention (PCI) bleeding complications which are associated with a high risk for subsequent clinical outcomes. The aim of this study was to estimate association between risk of gastrointestinal bleeding events related to proton pump inhibitor (PPI) use and subsequent clinical outcomes in patients with PCI. Methods The Clinical Deep Data Accumulation System (CLIDAS) is a database for inclusive of patient characteristics, medications, laboratory test, physiological test, cardiac catheterization and PCI treatment, all of which were aggregated from electronic medical records in 7 tertiary hospitals in Japan. Data of 6457 patients who underwent PCI between April 2014 and March 2020 and were then followed for 30 days after the index PCI, were analyzed. These patients were divided into two groups based on use of PPI; the PPI group (n=5285; 82%) and the non-PPI group (n=1172; 18%). Clinical outcomes, defined as gastrointestinal bleeding and all-cause death, were assessed using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) models. Results Among the 6457 PCI patients, 90 (1.7%) in the PPI group and 31 (2.6%) in the non-PPI group experienced gastrointestinal bleeding events. Adjusting for baseline demographics, comorbidities, and anti-thrombotic treatments, the multivariable Cox hazard model suggested a trend towards a lower risk of gastrointestinal bleeding with PPI use (HR, 0.70; 95%CI, 0.46-1.05; p=0.087). The PSM analysis confirmed a significant association between PPI use and a lower risk of gastrointestinal bleeding (HR, 0.13; 95%CI, 0.04-0.43; p=0.001), consistent with IPTW model results (HR, 0.60; 95%CI, 0.38-0.95; p=0.031). Subgroup analysis showed that PPI use was associated with a low risk of all-cause death in patients with acute coronary syndrome (ACS) (HR, 0.58; 95%CI, 0.36-0.93; p=0.024). Causal mediation analysis indicated an indirect effect of PPI on reducing all-cause death through the suppression of gastrointestinal bleeding events. Conclusion These findings suggested that use of PPI against gastrointestinal bleeding complications might reduce the risk of subsequent all-cause death in ACS patients undergoing PCI.

Proton pump inhibitors and cardiovascular risk: a critical review.

Proton pump inhibitors (PPI) are widely used medications for gastrointestinal disorders. Recent research suggests a potential association between long-term PPI use and increased cardiovascular (CV) risk, creating a complex clinical dilemma. This review critically evaluates the current evidence for this association, considering the limitations of observational studies and the lack of definitive confirmation from randomized controlled trials.This review delves into the reported association between PPIs and adverse CV events, examining proposed mechanisms such as drug interactions, electrolyte imbalances induced by PPIs and their potential impact on cardiac and vascular function. Evidence suggests these mechanisms converge, with varying influence depending on patient populations.Clinicians require a risk-benefit analysis for each patient considering their CV risk profile. Alternative gastrointestinal therapies should be explored for high-bleeding risk patients. Medications with lower cytochrome-P450 interaction potential may be preferable among essential PPI users. Elucidating the specific mechanisms by which PPIs might influence CV health, assessing long-term vascular effects and investigating interactions with newer anticoagulant medications are crucial for future research.

Proton-pump inhibitor use in older adults: Public vs. Private Prescribing in Portugal

Abstract Background Proton pump inhibitors (PPI) are frequently overprescribed, posing challenges to patients and healthcare systems. In Portugal, the publicly funded National Health Service (NHS) provides universal coverage and reimburses the cost of medications regardless of the prescription origin. If private practices may benefit from longer consultation times allowing better prescription, they do not face any incentive to avoid over-prescription. We aimed to compare outpatient prescription trends, patterns, and costs of PPI among older adults in private and public sectors. Methods Nationwide retrospective ecological study on PPI prescribed for older adults in Portugal 2020-2022. Data on defined daily doses (DDD) and costs were obtained from a national public database by healthcare sector, sex (female/male), and age group (65-74, ≥75). We analysed trends, market share of DDD per 1000 older adults per day (DID), and mean cost per DDD (€/DDD) for all PPI substances. Results We observed a decrease in prescribed PPI from 349.0 DID in 2020 to 341.9 DID in 2022. Omeprazole (reference and cheaper substance) was the most prescribed drug for females and pantoprazole for males in the public sector. Similar pattern was observed among those aged ≥75 in the private sector while for those aged 65-74, esomeprazole was the most prescribed drug. Overall, the private sector prescribed PPI with a 20% higher price (0.126 €/DDD) than the public (0.106 €/DDD), with greater differences among the most expensive substances (rabeprazole +0.032 €/DDD; lansoprazole +0.029 €/DDD; esomeprazole +0.021 €/DDD). Conclusions PPI prescription followed similar trends in both sectors, but private practitioners tend to prescribe more expensive drugs, because their patients can afford them and because there is no incentive for more rational prescription. Since the NHS financially supports drugs prescribed in private practices, financial incentives towards rationale prescription should also fall in this sector. Key messages • Overall, the private sector prescribed PPI with a 20% higher price (0.126 €/DDD) than the public (0.106 €/DDD), with greater differences among the most expensive substances. • Since the National Health Service financially supports drugs prescribed in private practices, financial incentives towards rationale prescription should also fall in this sector.

Temporal trends in major bleeding after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction from 2003 to 2017: the Western Denmark Heart Registry

Abstract Background Management of patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) has changed during the last two decades. Introduction of more potent platelet inhibitors may carry an increased risk of bleeding complications, while other therapeutic options, such as use of radial artery access and proton pump inhibitors may reduce bleeding risk. The combined impact of these treatment changes on bleeding risk in patients with STEMI remains unknown. Purpose To examine temporal trends in 1-year risk of major bleeding after STEMI treated with primary PCI from 2003 to 2017. Methods We used the Western Denmark Heart Registry to identify first-time PCI-treated patients undergoing primary PCI for STEMI from 2003 to 2017. Patients were divided into 4 calendar periods based on the time of STEMI. The main outcome was 1-year risk of major bleeding defined as a hospital admission for bleeding using a validated definition with high accuracy. Additionally, the 1-year risk of major bleeding in STEMI patients was compared with the risk in an age- and sex-matched general population cohort without prior coronary artery disease. Results From 2003 to 2017, we identified 18,540 patients treated with primary PCI for STEMI (median age 64 years, 75% men)and 92,700 age- and sex-matched individuals. The 1-year risk of major bleeding after STEMI was similar across the different time periods; 4.1% in 2003-2006, 3.8% in 2007-2010, 3.8% in 2011-2014, and 4.5% in 2015-2017. The adjusted HR for bleeding in STEMI patients was 1.03 (95% CI 0.83-1.26) when comparing the latest period with the earliest period. The age- and sex-matched general population exhibited a 1-year risk of major bleeding of around 1% in all time periods (Figure 1). Conclusions Despite changes in management, the 1-year risk of major bleeding remained stable around 4% after primary PCI-treated STEMI from 2003 to 2017. This risk was approximately 4 times higher than the bleeding risk observed in an age- and sex-matched general population.

Development and validation of a training course on proton pump inhibitor deprescription for general practitioners in a rural continuing medical education program: a pilot study

BackgroundDespite being cornerstone medications for managing gastrointestinal disorders, proton pump inhibitors (PPI) have raised concerns due to inappropriate prescribing and overutilization, their potential side effects, and interactions with other medications. General practitioners (GPs) provide long-term patient follow-up and are targets to promote PPI deprescribing to reach the widest possible population. GPs practicing in rural settings encounter unique challenges as their numbers dwindle and their workload increases. Hence, targeted educational interventions are crucial to promote appropriate prescribing practices in such underserved areas.MethodsWe developed a continuing medical education (CME) program focused on PPI deprescribing for GPs in rural settings. The program comprised of an interactive training session featuring clinical cases, an open discussion, and distribution of educational materials. We assessed the program’s effectiveness using a two-level Kirkpatrick model, evaluating participant satisfaction and knowledge levels through pre- and post-course questionnaires.ResultsThirty-three GPs participated, with 61.9% working in semi-rural and 38.1% in rural areas (21 responded to the 1st questionnaire, 14 to the 2nd ). Median medical experience was 6 years, with 61.9% serving as internship supervisors. Despite 95.2% acknowledging PPI overprescription, none had previously participated in dedicated PPI CME programs. The open discussion session provided valuable insights into various topics related to PPI use and gastrointestinal health. Participants expressed high satisfaction with the program (average rating of 9.1/10) and 92.9% reported changes in practice, including increased awareness of inappropriate PPI prescriptions. Indeed, 92.9% of GPs identified inappropriate PPI use following the course. 57.1% of participants utilized the provided educational materials. The main practice changes observed included an increased reassessment rate of PPI indications (71.4% at each renewal after vs. 19% before, 28.6% non-systematically after vs. 66.8% before, 0% rarely after vs. 14.3% before; p = 0.006), the necessity for more than one consultation to deprescribe (64.3% after vs. 23.8% before; p = 0.021), systematic utilization of gradual cessation of PPI (100% vs. 61.9%; p = 0.039) and more frequent use of additional medication (92.9% vs. 57.1%; p = 0.022), primarily antiacids (92.3%).ConclusionsOur study underscores the effectiveness of targeted CME programs in promoting appropriate prescribing practices and enhancing knowledge among GPs in rural settings. Despite the challenges encountered in deprescribing PPI, the program facilitated proactive approaches in managing treatment discontinuation failures. Tailored educational interventions are essential for mitigating medication prescribing challenges and improving patient outcomes in rural primary care settings.Trial registrationsNot applicable.

Association Between the Use of Proton Pump Inhibitors and Severe Clinical Outcomes in COVID-19 Patients: A Retrospective Observational Study.

Background Proton pump inhibitors (PPIs) increase the risk of pneumonia secondary to PPI-induced hypochlorhydria. We aim to investigate the association between PPI and disease severity in coronavirus disease 2019 (COVID-19)-positive patients and the risk of hospitalizations in Muscat, Oman. Methodology COVID-19-positive patients aged 18 years and above at the time of diagnosis were included in this retrospective observational study. The details of the patients were retrieved from the electronic health records of the Al Shifa Hospital Information Management System and Tarassud. The composite primary endpoint was COVID-19 admission to a government tertiary hospital ward or intensive care within 14 days of diagnosis. Results A total of 506 COVID-19-positive patients were identified during the specified period. The mean age was 44 ± 15 years. The majority of the patients were Omani, and a female preponderance was observed. Overall, 104 (20.4%) patients were current PPI users. Admission due to COVID-19 was significantly associated with the presence of comorbid conditions such as diabetes mellitus (p = 0.001), hypertension (p = 0.001), and chronic kidney disease (p < 0.001). However, current PPI use (p = 0.140) was not significantly associated with an increased risk of hospitalization. Conclusions This data suggests that the use of PPIs during COVID-19 infection did not increase the risk of severe COVID-19 infection and poor outcomes leading to hospitalization in Muscat, Oman. However, the presence of other medical comorbidities, such as diabetes and hypertension, was associated with a higher risk of adverse clinical symptoms that resulted in hospitalization.

Evolution of the use, effectiveness and safety of bismuth-containing quadruple therapy for Helicobacter pylori infection between 2013 and 2021: results from the European registry on H. pylori management (Hp-EuReg)

BackgroundBismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of...

Disorders of secondary peristalsis are associated with the development of esophagitis.

Disorders of primary peristalsis are associated with a higher percent time pH <4 in the esophagus suggesting poor acid clearance. However, there are no studies of secondary peristalsis and its relationship to microscopic or erosive esophagitis. The goal of this study was to determine the relationship between secondary peristalsis using functional luminal imaging probes (EndoFLIP) and the presence or absence of esophagitis. We reviewed the endoscopic and EndoFLIP 2.0 tracings for 103 consecutive patients including those with a history of upper gastrointestinal surgery undergoing upper endoscopy. Esophagogastric junction (EGJ) distensibility and diameter, repetitive antegrade contraction (RACs) presence and frequency, and occlusive diameters were measured. Measurements were then compared between patients with and without microscopic and/or erosive esophagitis. Means were compared using t-tests. Proportions were compared using Chi-Squared analyses. One hundred and three patients were included (mean age: 14.4 + 6.4 years). Ten patients had erosive esophagitis and 28 patients had microscopic esophagitis. Erosive and microscopic esophagitis were associated with abnormal or absent of RACs (p < 0.001). Occlusive diameters were higher in patients with esophagitis compared to those without (p < 0.001). There was no relationship between EGJ distensibility and the presence of erosive or microscopic esophagitis (p = 0.4). The absence of RACs was the only independent predictor of esophagitis (erosive and microscopic), after controlling for age, proton pump inhibitors (PPI) use and EGJ distensibility (p < 0.001). Abnormal secondary peristalsis is associated with microscopic and gross esophagitis, suggesting that EndoFLIP should be part of the diagnostic algorithm for esophagitis.

Association between magnesium depletion score and periodontitis in US adults: results from NHANES 2009–2014

BackgroundThis study aims to explore the relationship between magnesium depletion score (MDS) and periodontitis in US adults using data from the National Health and Nutritional Examination Survey (NHANES) 2009–2014.MethodsThis cross-sectional study’s outcome was periodontitis, defined by the CDC/AAP using clinical periodontal parameters. The exposure of this study was MDS, which was calculated according to four parameters (diuretic use, proton pump inhibitor use, renal function and alcohol consumption). Weighted univariable and multivariable logistic regression analyses were performed to explore the association between MDS intake and periodontitis. Confounding factors included in the adjusted model were age, sex, race, income, smoking status, dietary magnesium, obesity, diabetes, hypertension, education level, recreational activity, and work activity.ResultsA total of 8,628 participants over the age 30 were included in our study. Individuals with high level of magnesium deficiency were more likely referred to poorer periodontal health in both crude model (OR = 2.01, 95% CI: 1.54–2.61, p < 0.0001) and fully adjusted model (OR = 1.35, 95% CI: 1.03–1.77, p = 0.03).ConclusionsMDS is positively associated with moderate/severe periodontitis. Further longitudinal studies are needed to understand the impact of MDS on periodontitis.

Pharmacological Correction of Gastrointestinal Motility in Patients with Functional Gastrointestinal Disorders

Actuality. Functional gastrointestinal disorders (FGID) represent a significant public public health issue. The foundation of effective therapy for FGID with overlap syndrome - functional dyspepsia (FD, epigastric pain syndrome) with gastric hypersecretion and irritable bowel syndrome (IBS)-is considered to be pathogenetic therapy or the combined use of symptomatic medications. Aim. Assessment of the impact of pathophysiological therapy with the drug Kolofort and symptomatic treatments, including proton pump inhibitors (PPIs) and the myotropic antispasmodic mebeverine hydrochloride in prolonged-release capsules, on the clinical manifestations of FGIDs with overlap syndrome - FD (pain syndrome in the epigastric region) with gastric hypersecretion and IBS - includes evaluating effects on myoelectric activity of the gastrointestinal tract. Design. (conception) An open cohort-controlled comparative study on the effects of Kolofort, omeprazole, rabeprazole, and mebeverine hydrochloride in prolonged-release capsules on intestinal motility in patients with FGID and overlap syndrome - functional dyspepsia (FD, epigastric pain syndrome) with gastric hypersecretion and IBS. Materials and Methods. A total of 107 patients suffering from FGID with overlap syndrome - functional dyspepsia (FD, epigastric pain syndrome) with gastric hypersecretion and IBS - were examined. Results. A one-month course of Kolofort significantly improved the psychological status of IBS patients and enhanced intestinal myoelectric activity. Since there is no available literature on Kolofort’s effect on gastric secretion levels, PPIs and mebeverine hydrochloride were used in the treatment of patients with FGID - FD (epigastric pain syndrome) with gastric hypersecretion and IBS overlap syndrome. The use of PPIs, such as omeprazole and rabeprazole, in these patients eliminated gastric hypersecretion and abdominal pain. Rabeprazole demonstrated faster effects than omeprazole and also normalized gastrointestinal motility more efficiently. For patients with FGIDs - FD with gastric hypersecretion and overlap syndrome with IBS, a combined therapy of omeprazole and the myotropic antispasmodic mebeverine hydrochloride in prolonged-release capsules is recommended. This combination, within two weeks, resolved clinical symptoms in 97% of cases, improved the quality of life, and normalized intestinal motility and gastrointestinal myoelectric activity. However, monotherapy with rabeprazole at a daily dose of 20 mg more rapidly addressed symptoms of gastric hypersecretion and and normalized gastrointestinal motility.

Comparison of Vicious Effect of Oral Pantoprazole and Famotidine on New Bone Formation in Patients With Lumbar Spine Fusion Surgery: A Randomized Control Trial

Background and Aim: Due to the increasing use of proton pump inhibitors (PPIs) and their side effects for bone repair and the high percentage of therapy failure in lumbar fusion surgery, especially in various animal studies, the goal of this study was to appraise the consequence of pantoprazole and famotidine on new bone formation in patients experiencing spinal fusion surgery. Methods and Materials/Patients: In this double-blind clinical trial, eighty patients participated based on the inclusion and exclusion criteria, of whom 40 cases received pantoprazole (group P) and 40 received famotidine (group F) for eight weeks. They were followed up for three, six, and twelve months after surgery for cage subsidence, screw loosening, and visual analogue scale (VAS), Oswestry disability index (ODI), Brantigan, Steffee, Fraser (BSF), and Lenke classification for grading their bone formation. A P&lt;0.05 was considered significant. Results: The rate of fusion based on the Lenke score was lower in the group receiving pantoprazole six and 12 months after the surgery compared to group F (the frequency of Lenke grades C and D were 35% and 25% compared to the famotidine group 12.5% and 12.5%, respectively; P=0.042). The VAS Mean±SD score in group F was lower than group P after 12 months (2.48±1.06 and 1.83±0.55, respectively; P=0.008). There was no pharmacologically significant association between subsidence (P=0.43), loosening (P=0.13), ODI (P=0.31), and BSF (P=0.77) 3, 6 and 12 months post-operation. Conclusion: Affording to the preliminary conclusions of this study, the use of pump inhibitors, such as pantoprazole is more destructive for the ossification process in candidates for spinal fusion requiring the chronic use of drugs for controlling their gastric acid secretion, and H2-blocking drugs, such as famotidine are preferable in this situation after further investigations.

Multicenter study on Clostridioides difficile infections in Mexico: exploring the landscape.

This study aims to outline Clostridioides difficile infection (CDI) trends and outcomes in Mexican healthcare facilities during the COVID-19 pandemic. Observational study of case series. Sixteen public hospitals and private academic healthcare institutions across eight states in Mexico from January 2016 to December 2022. CDI patients. Demographic, clinical, and laboratory data of CDI patients were obtained from clinical records. Cases were classified as community or healthcare-associated infections, with incidence rates calculated as cases per 10,000 patient days. Risk factors for 30-day all-cause mortality were analyzed by multivariate logistic regression. We identified 2,356 CDI cases: 2,118 (90%) were healthcare-associated, and 232 (10%) were community-associated. Common comorbidities included hypertension, diabetes, and cancer. Previous high use of proton-pump inhibitors, steroids, and antibiotics was observed. Recurrent infection occurred in 112 (5%) patients, and 30-day mortality in 371 (16%). Risk factors associated with death were a high Charlson score, prior use of steroids, concomitant use of antibiotics, leukopenia, leukocytosis, elevated serum creatine, hypoalbuminemia, septic shock or abdominal sepsis, and SARS-CoV-2 coinfection. The healthcare-associated CDI incidence remained stable at 4.78 cases per 10,000 patient days during the pre-and pandemic periods. However, the incidence was higher in public hospitals. Our study underscores the need for routine epidemiology surveillance and standardized CDI classification protocols in Mexican institutions. Though CDI rates in our country align with those in some European countries, disparities between public and private healthcare sectors emphasize the importance of targeted interventions.

Proton pump inhibitor use and risk of stroke: A systematic review and meta-analysis

Objective: To explore a link between the use of proton pump inhibitor (PPI) and the risk of stroke. Methods: Comprehensive literature search in PubMed, EMBASE, and Cochrane CENTRAL Library databases was carried out for observational studies establishing the link between PPI and a risk of stroke. Data extraction and quality assessment were performed by two reviewers. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) using random-effects models were plotted. Subgroup analyses were conducted based on age, gender, PPI type, duration of follow-up, and propensity score matching (PSM). Results: The analysis included 12 studies, with considerable heterogeneity (I2 = 95%). PPI use did not affect the incidence of ischemic stroke (HR: 1.11, 95% CI: 0.98-1.26). Subgroup analyses revealed that PPI use correlated with the risk of ischemic stroke, in particular in patients&lt;65 years old (HR: 1.25, 95% CI: 1.07-1.45), both males (HR: 1.12, 95% CI: 1.02-1.24) and females (HR: 1.21, 95% CI: 1.10-1.33). The correlation varied depending on the PPI type, with pantoprazole showing elevated risk (HR: 1.66, 95% CI: 1.43-1.93). Duration of follow-up or propensity score matching (PSM) did not impact the association. Conclusion: PPI use may be linked with ischemic stroke, particularly in individuals &lt;65 years old and of all genders. The specific PPI type may also influence the risk. However, the cumulative analysis did not find any statistically significant association, and heterogeneity among studies was substantial. PROSPERO Registration Number: CRD42023422247. doi: https://doi.org/10.12669/pjms.40.10.10409 How to cite this: Feng Y, Zhong Y. Proton pump inhibitor use and risk of stroke: A systematic review and meta-analysis. Pak J Med Sci. 2024;40(10):2432-2440. doi: https://doi.org/10.12669/pjms.40.10.10409 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Association between magnesium depletion score and the risk of metabolic dysfunction associated steatotic liver disease: a cross sectional study

The relationship between magnesium deficiency and metabolic dysfunction associated steatotic liver disease (MASLD) remains unclear. This study aimed to examine the association between the magnesium depletion score (MDS) and the risk of MASLD, as well as explore potential underlying mechanisms. Data from 12,024 participants from the National Health and Nutrition Examination Survey (NHANES) 2005–2018 were analyzed. MDS was calculated based on the use of diuretics and proton pump inhibitors, kidney function, and alcohol consumption. MASLD was defined using the fatty liver index. Logistic regression, restricted cubic spline analysis, and mediation analyses were conducted to evaluate the association between MDS and MASLD and to identify potential mediators. A higher MDS was significantly associated with an increased risk of MASLD (OR = 2.00, 95% CI [1.47, 2.74] for MDS 3 vs. 0). A dose-response relationship between MDS and MASLD risk was observed. Neutrophils, albumin, and white blood cells partially were identified as partial mediators of the association, with albumin exhibiting the highest mediating effect (14.05%). Elevated MDS is significantly associated with an increased risk of MASLD in U.S. adults. Inflammation and albumin may serve as potential mediators of this relationship. These findings underscore the importance of addressing magnesium deficiency in the prevention and management of MASLD.

Use of proton pump inhibitors and risk of severe COVID-19: A case-control study in United States Medicare beneficiaries.

Concerns have been raised regarding proton pump inhibitor (PPI) use and risk of severe coronavirus disease 2019 (COVID-19). Observational studies have yielded heterogeneous results and were subject to important methodological limitations. To examine the association between the receipt of PPIs and risk of COVID-19 hospitalizations and severe in-hospital outcomes or death. Case-control study among Medicare fee-for-service beneficiaries 66+ years old with gastroesophageal reflux disorder (GERD). Within this population, we identified cases by an incident hospital discharge diagnosis of COVID-19 from April 1 to December 11, 2020, using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) U07.1, and randomly selected up to 10 controls per case, matched on date and neighborhood. We defined PPI use as a prescription providing ≥15 days of supply in the 30 days before admission, with H2-receptor antagonist (H2RA) use as the reference to account for indication. We analyzed uncomplicated hospitalizations and hospitalizations with severe outcomes (intensive/coronary care unit admission, invasive mechanical ventilation, or death), estimating odds ratios (ORs), and 95% confidence intervals (CIs) with multinomial conditional logistic regression adjusted for demographics, comorbidities, chronic medications, and health care utilization. We matched 25,867 uncomplicated and 12,954 severe hospitalized COVID-19 cases to 146,972 and 73,104 controls, respectively. Cases tended to be older and have more comorbidities. Relative to H2RA use, we found no association of PPI use with uncomplicated COVID-19 hospitalization (OR 0.99, 95% CI 0.93-1.06) or severe COVID-19 hospitalization (OR 1.00, 95% CI 0.91-1.10). Relative to H2RA use, PPI use was not associated with uncomplicated or severe COVID-19 hospitalizations among Medicare beneficiaries with GERD.

Pattern of Prescribing Proton Pump Inhibitors: Evaluating Appropriateness and Factors Contributing to Their Adverse Effect Reaction Risk.

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.

The biogeography of the mucosa-associated microbiome in health and disease.

Little is known about the biogeography of the mucosa associated microbiome (MAM) in patients with inflammatory bowel disease (IBD) versus controls in different segments of the gastrointestinal tract, as well as the links between the MAM, gastrointestinal symptoms, and use of proton pump inhibitors (PPI). We recruited 59 controls (without structural abnormalities and gastrointestinal symptoms), 44 patients with ulcerative colitis (UC) and 31 with Crohn's disease (CD). Biopsies from various segments of the upper and lower gastrointestinal tract were collected. Microbial composition was assessed via 16S rRNA gene amplicon analysis and the bacterial load of the mucosal biopsies were assessed via qPCR. The MAM was examined in the context of disease status, PPI usage, the severity of gastrointestinal symptoms, and the symptom response to a standardised nutrient challenge (SNC). Microbial communities of the MAM in the upper and lower gastrointestinal tract differed. IBD patients were characterised by relative and absolute depletion of numerous genera known to produce butyrate and/or propionate, with the largest differentiation being the depletion of Faecalibacterium in the lower gastrointestinal tract of CD patients. Notably, PPI users exhibited an enrichment of Faecalibacterium in the lower gastrointestinal tract. The severity of gastrointestinal symptoms, as well as the symptom response to the SNC, were significantly associated with MAM composition in the gastrointestinal tract. The absolute and relative composition of the MAM is variable across different segments of the gastrointestinal tract. These quantitative changes indicates that MAM can be targeted in specific segments of the GI tract to improve patient outcomes.

Association between gastroprotective agents and acute kidney injury in patients receiving non-steroidal anti-inflammatory drugs: Analysis of a Japanese hospital-based database.

The concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) potentially increases the risk of acute kidney injury (AKI). However, the risk of AKI has not been comprehensively assessed for the concomitant use of NSAIDs with gastroprotective agents such as misoprostol and PPIs. The objective of this study was to evaluate whether the use of various gastroprotective agents affects the risk of AKI in patients receiving NSAIDs. The data analyzed were obtained from the JMDC hospital-based administrative claims database between April 2014 and August 2022. Histamine-2 receptor antagonists (H2RAs) were compared with PPIs or misoprostol in patients receiving NSAIDs. The primary outcome was the incidence of AKI. The covariates considered were age and sex, admission to intensive care unit, presence of comorbidities based on the modified Charlson Comorbidity Index, and use of renin-angiotensin system inhibitors, loop diuretics, other diuretics, and lithium. AKI was identified by changes in serum creatinine. The distribution of AKI was analyzed using the log-rank test, and estimates of the incidence of AKI were compared among the groups using a Cox proportional hazards model with time-varying variables. Models were adjusted using a doubly robust method that accounts for the inverse probability of treatment weighting at baseline while adjusting for covariates. After screening, 11,688 patients were eligible for inclusion (1729 for H2RAs, 368 for misoprostol, and 9591 for PPIs). AKI occurred in 0.5% of H2RA recipients and 1.1% of PPI recipients; no AKI was observed in the misoprostol group. Compared with H2RAs, the risk of AKI tended to be higher with PPIs (adjusted hazard ratio 1.83, 95% confidence interval 0.92-3.63, p = 0.08). Compared with H2RAs, PPIs may increase the risk of AKI in patients receiving NSAIDs, although no statistically significant difference was observed. Further research is required to assess the risk trade-off with consideration of both peptic ulcer prevention and the increased risk of AKI in patients concurrently treated with NSAIDs and H2RAs, misoprostol, or PPIs.