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The American Journal of Gastroenterology Nov 2023In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are... (Randomized Controlled Trial)
Randomized Controlled Trial
Poliprotect vs Omeprazole in the Relief of Heartburn, Epigastric Pain, and Burning in Patients Without Erosive Esophagitis and Gastroduodenal Lesions: A Randomized, Controlled Trial.
INTRODUCTION
In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are widely used, alone or as add-on treatment, to increase response to proton-pump inhibitors, which are not indicated in infancy and pregnancy and account for significant cost expenditure.
METHODS
In this randomized, controlled, double-blind, double-dummy, multicenter trial assessing the efficacy and safety of mucosal protective agent Poliprotect (neoBianacid, Sansepolcro, Italy) vs omeprazole in the relief of heartburn and epigastric pain/burning, 275 endoscopy-negative outpatients were given a 4-week treatment with omeprazole (20 mg q.d.) or Poliprotect (5 times a day for the initial 2 weeks and on demand thereafter), followed by an open-label 4-week treatment period with Poliprotect on-demand. Gut microbiota change was assessed.
RESULTS
A 2-week treatment with Poliprotect proved noninferior to omeprazole for symptom relief (between-group difference in the change in visual analog scale symptom score: [mean, 95% confidence interval] -5.4, -9.9 to -0.1; -6.2, -10.8 to -1.6; intention-to-treat and per-protocol populations, respectively). Poliprotect's benefit remained unaltered after shifting to on-demand intake, with no gut microbiota variation. The initial benefit of omeprazole was maintained against significantly higher use of rescue medicine sachets (mean, 95% confidence interval: Poliprotect 3.9, 2.8-5.0; omeprazole 8.2, 4.8-11.6) and associated with an increased abundance of oral cavity genera in the intestinal microbiota. No relevant adverse events were reported in either treatment arm.
DISCUSSION
Poliprotect proved noninferior to standard-dose omeprazole in symptomatic patients with heartburn/epigastric burning without erosive esophagitis and gastroduodenal lesions. Gut microbiota was not affected by Poliprotect treatment. The study is registered in Clinicaltrial.gov (NCT03238534) and the EudraCT database (2015-005216-15).
Topics: Humans; Omeprazole; Heartburn; Anti-Ulcer Agents; Esophagitis; Proton Pump Inhibitors; Dyspepsia; Peptic Ulcer; Abdominal Pain; Treatment Outcome; Double-Blind Method
PubMed: 37307528
DOI: 10.14309/ajg.0000000000002360 -
Journal of Translational Medicine May 2024A former cohort study has raised concern regarding the unanticipated hazard of omeprazole in expediting osteoarthritis (OA) advancement. The precise nature of their...
BACKGROUND
A former cohort study has raised concern regarding the unanticipated hazard of omeprazole in expediting osteoarthritis (OA) advancement. The precise nature of their causal evidence, however, remains undetermined. The present research endeavors to investigate the underlying causal link between omeprazole and OA through the application of mendelian randomization (MR) analysis.
METHODS
The study incorporated the ukb-a-106 and ukb-b-14,486 datasets. The investigation of causal effects employed methodologies such as MR-Egger, Weighted median, Inverse variance weighted (IVW) with multiplicative random effects, and IVW (fixed effects). The IVW approach was predominantly considered for result interpretation. Sensitivity analysis was conducted, encompassing assessments for heterogeneity, horizontal pleiotropy, and the Leave-one-out techniques.
RESULTS
The outcomes of the MR analysis indicated a causal relationship between omeprazole and OA, with omeprazole identified as a contributing risk factor for OA development (IVW model: OR = 1.2473, P < 0.01 in ukb-a-106; OR = 1.1288, P < 0.05 in ukb-b-14,486). The sensitivity analysis underscored the robustness and dependability of the above-mentioned analytical findings.
CONCLUSION
This study, employing MR, reveals that omeprazole, as an exposure factor, elevates the risk of OA. Considering the drug's efficacy and associated adverse events, clinical practitioners should exercise caution regarding prolonged omeprazole use, particularly in populations with heightened OA risks. Further robust and high-quality research is warranted to validate our findings and guide clinical practice.
Topics: Humans; Omeprazole; Mendelian Randomization Analysis; Osteoarthritis; United Kingdom; Biological Specimen Banks; Risk Factors; Female; Male; Middle Aged; UK Biobank
PubMed: 38802944
DOI: 10.1186/s12967-024-05255-y -
Nature Communications Dec 2023Target trial emulation is the process of mimicking target randomized trials using real-world data, where effective confounding control for unbiased treatment effect...
Target trial emulation is the process of mimicking target randomized trials using real-world data, where effective confounding control for unbiased treatment effect estimation remains a main challenge. Although various approaches have been proposed for this challenge, a systematic evaluation is still lacking. Here we emulated trials for thousands of medications from two large-scale real-world data warehouses, covering over 10 years of clinical records for over 170 million patients, aiming to identify new indications of approved drugs for Alzheimer's disease. We assessed different propensity score models under the inverse probability of treatment weighting framework and suggested a model selection strategy for improved baseline covariate balancing. We also found that the deep learning-based propensity score model did not necessarily outperform logistic regression-based methods in covariate balancing. Finally, we highlighted five top-ranked drugs (pantoprazole, gabapentin, atorvastatin, fluticasone, and omeprazole) originally intended for other indications with potential benefits for Alzheimer's patients.
Topics: Humans; Alzheimer Disease; Drug Repositioning; Propensity Score; Atorvastatin
PubMed: 38081829
DOI: 10.1038/s41467-023-43929-1 -
World Journal of Cardiology Aug 2023Aspirin, other antiplatelet agents, and anticoagulant drugs are used across a wide spectrum of cardiovascular and cerebrovascular diseases. A concomitant proton pump... (Review)
Review
Aspirin, other antiplatelet agents, and anticoagulant drugs are used across a wide spectrum of cardiovascular and cerebrovascular diseases. A concomitant proton pump inhibitor (PPI) treatment is often prescribed in these patients, as gastrointestinal complications are relatively frequent. On the other hand, a potential increased risk of cardiovascular events has been suggested in patients treated with PPIs; in particular, it has been discussed whether these drugs may reduce the cardiovascular protection of clopidogrel, due to pharmacodynamic and pharmacokinetic interactions through hepatic metabolism. Previously, the concomitant use of clopidogrel and omeprazole or esomeprazole has been discouraged. In contrast, it remains less known whether PPI use may affect the clinical efficacy of ticagrelor and prasugrel, new P2Y12 receptor antagonists. Current guidelines recommend PPI use in combination with antiplatelet treatment in patients with risk factors for gastrointestinal bleeding, including advanced age, concurrent use of anticoagulants, steroids, or non-steroidal anti-inflammatory drugs, and () infection. In patients taking oral anticoagulant with risk factors for gastrointestinal bleeding, PPIs could be recommended, even if their usefulness deserves further data. infection should always be investigated and treated in patients with a history of peptic ulcer disease (with or without complication) treated with antithrombotic drugs. The present review summarizes the current knowledge regarding the widespread combined use of platelet inhibitors, anticoagulants, and PPIs, discussing consequent clinical implications.
PubMed: 37771340
DOI: 10.4330/wjc.v15.i8.375 -
Leukemia Dec 2023Dasatinib monohydrate indicated for the treatment of chronic myeloid leukemia displays pH-dependent solubility. The aim of reported development program of novel...
Dasatinib monohydrate indicated for the treatment of chronic myeloid leukemia displays pH-dependent solubility. The aim of reported development program of novel dasatinib anhydrate containing formulation was to demonstrate improved absorption and lower pharmacokinetic variability compared to dasatinib monohydrate. In a bioavailability study comparing formulations containing 110.6 mg and 140 mg of dasatinib as anhydrate and monohydrate, respectively, both C and AUC of dasatinib were within standard 80.00-125.00% range, while the intra- and inter-subject variability for AUC after the test product was approximately 3-fold and 1.5-fold less than after the reference, respectively.In a drug-drug interaction study, omeprazole 40 mg reduced the mean AUC of dasatinib by 19%, when the test was ingested 2 h before the 5th omeprazole dose. This decrease of exposure is clinically irrelevant and substantially less than after the reference. Co-prescription analysis supports the importance of pH-dependent solubility of dasatinib, as >21% of patients were treated concomitantly with a PPI and dasatinib despite warnings against this co-medication in the SmPC.The novel dasatinib anhydrate containing formulation demonstrated improved absorption and less pharmacokinetic variability compared to dasatinib monohydrate product, which may translate into improved clinical outcomes, although this needs to be proven by an appropriate trial.
Topics: Humans; Dasatinib; Biological Availability; Omeprazole; Cross-Over Studies; Area Under Curve; Administration, Oral
PubMed: 37789147
DOI: 10.1038/s41375-023-02045-1 -
Medicine Nov 2023The objective of this study was to explore the causal relationship between the use of proton pump inhibitors (PPIs) and 16 types of digestive system tumors. We utilized...
The objective of this study was to explore the causal relationship between the use of proton pump inhibitors (PPIs) and 16 types of digestive system tumors. We utilized a 2-sample Mendelian randomization (MR) approach to investigate this relationship. We obtained exposure and outcome data from the UK Biobank and the Finland Biobank, respectively. The genetic data used in the analysis were derived from genome-wide association studies (GWAS) studies conducted on European populations. We screened single nucleotide polymorphisms significantly associated with the use of omeprazole, a commonly used PPIs, as instrumental variables. We then performed MR analyses using the inverse variance weighting (IVW) method, MR-Egger regression, and the weighted median method to evaluate the causal effect of omeprazole use on the 16 types of digestive system tumors. Our MR analysis revealed a significant causal relationship between the use of omeprazole and pancreatic malignancies, but not with any other types of digestive system tumors. The IVW analysis showed an odds ratio of 4.33E-05 (95%CI: [4.87E-09, 0.38], P = .03) and the MR-Egger analysis showed an odds ratio of 5.81E-11 (95%CI: [2.82E-20, 0.12], P = .04). We found no significant heterogeneity or pleiotropy, and sensitivity analysis confirmed the robustness of our results. Furthermore, statistical power calculations suggested that our findings were reliable. Conclusion The use of PPIs is a protective factor for pancreatic malignancies, but no causal relationship has been found with other digestive system tumors.
Topics: Humans; Proton Pump Inhibitors; Genome-Wide Association Study; Mendelian Randomization Analysis; Digestive System Neoplasms; Gastrointestinal Neoplasms; Pancreatic Neoplasms; Omeprazole
PubMed: 37960715
DOI: 10.1097/MD.0000000000036085 -
Cureus Aug 2023Peptic ulcer disease (PUD) refers to the occurrence of an open erosion in the inner lining of the stomach, duodenum, or sometimes lower esophagus. Treatments like proton... (Review)
Review
Comparing the Safety and Efficacy of Proton Pump Inhibitors and Histamine-2 Receptor Antagonists in the Management of Patients With Peptic Ulcer Disease: A Systematic Review.
Peptic ulcer disease (PUD) refers to the occurrence of an open erosion in the inner lining of the stomach, duodenum, or sometimes lower esophagus. Treatments like proton pump inhibitors (PPIs) or histamine 2 receptor antagonists (H2RAs) are available on the market to efficiently treat the break in the mucosal lining. However, there is little evidence about the effects of the medication on the type and location of the ulcer and the epigastric pain caused by disintegration and increased acidity in the stomach. Given the above, we conducted a systematic review comparing the safety and efficacy of PPIs and H2RAs in various ulcer locations (gastric, duodenal, and pre-pyloric) and the effect of prolonging the treatment with the same medication or changing into a drug from another class in treatment-resistant ulcers. We employed major research literature databases and search engines such as PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), Science Direct, and Google Scholar to find relevant articles. After a thorough screening, a quality check using various tools, and applying filters that suited our eligibility criteria, we identified eight articles, of which five were random clinical trials (RCTs), two review articles, and one meta-analysis. This study compares the different side effects of PPIs and H2RAs. Most studies concluded that omeprazole is superior in healing ulcers and bringing pain relief and that patients resistant to H2RAs can be treated better when switched to a PPI. This study also discusses the adverse effects of chronic use, such as diarrhea, constipation, headaches, and gastrointestinal infections. Patients on long-term PPI therapy are required to take calcium supplements to prevent the risk of fractures in older adults. Regarding long-term outcomes, PPIs remain the mainstay of treatment for peptic ulcer disease, based on the papers we reviewed.
PubMed: 37779765
DOI: 10.7759/cureus.44341 -
OncoTargets and Therapy 2023Ovarian cancer is the most lethal malignancy in gynecology. Due to limited treatment strategies and platinum resistance, newer drugs and therapeutic options are needed....
PURPOSE
Ovarian cancer is the most lethal malignancy in gynecology. Due to limited treatment strategies and platinum resistance, newer drugs and therapeutic options are needed. Esomeprazole (ESO) has been reported to have multiple anticancer activities in preclinical and clinical research. Therefore, this study aimed to explore the anticancer effects of esomeprazole on ovarian cancer and its underlying molecular mechanisms.
METHODS
CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell viability and proliferation. The Transwell assay was used to evaluate cell migration and invasion capacity. Flow cytometry was used to detect cell apoptosis. Western blotting and immunofluorescence were used to detect protein expression.
RESULTS
ESO effectively inhibited the cell viability, proliferation, invasion, migration, and induced apoptosis of ovarian cancer cells in a concentration-dependent manner. Treatment with ESO decreased the expression of c-MYC, SKP2, E2F1, N-cadherin, vimentin, and matrix metalloproteinase 2 (MMP2), while it increased E-cadherin, caspase3, p53, BAX, and cleaved poly (ADP-ribose) polymerase (PARP) expression, and downregulated the PI3K/AKT/mTOR signaling pathway. Furthermore, ESO combined with cisplatin showed synergistic effects in inhibiting proliferation, invasion, and migration of cisplatin-resistant ovarian cancer cells. The mechanism may be related to the increased inhibition of c-MYC, epithelial-mesenchymal transition (EMT), and the AKT/mTOR signaling pathway and enhanced the upregulation of the pro-apoptotic protein BAX and cleaved PARP levels. Moreover, ESO combined with cisplatin synergistically upregulated the expression of the DNA damage marker γH2A.X.
CONCLUSION
ESO exerts multiple anticancer activities and has a synergistic effect in combination with cisplatin on cisplatin-resistant ovarian cancer cells. This study provides a promising strategy to improve chemosensitivity and overcome resistance to cisplatin in ovarian cancer.
PubMed: 37359351
DOI: 10.2147/OTT.S406009