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Food Technology and Biotechnology Dec 2023The role of dietary habits of patients with laryngopharyngeal reflux (LPR) is comparatively underexplored. The aim of the study is to examine dietary habits, onset and...
RESEARCH BACKGROUND
The role of dietary habits of patients with laryngopharyngeal reflux (LPR) is comparatively underexplored. The aim of the study is to examine dietary habits, onset and course of the disease as well as the quality of life of patients with LPR.
EXPERIMENTAL APPROACH
The results of the modified food frequency questionnaire (FFQ-m) and laryngopharyngeal reflux health-related quality of life (LPR-HRQL) questionnaires were compared between subjects with and without LPR. There were a total of 100 subjects with LPR and 65 subjects in the control group. The group of subjects with LPR was further randomly divided into two subgroups; the first subgroup was treated with esomeprazole at a dose of 20 mg twice daily combined with the instructions for dietary and general lifestyle changes, and the other with pantoprazole at a dose of 20 mg twice daily combined with the instructions for dietary and general lifestyle changes. Participants were instructed to fill out FFQ-m and LPR-HRQL questionnaires immediately after the initial examination and then after control examinations 30 and 60 days after the initial examination.
RESULTS AND CONCLUSIONS
Patients with LPR consume more food with high reflux potential, drink more carbonated drinks and juices and have a worse quality of life than the control group (p<0.001). Taking proton pump inhibitors at a dose of 20 mg twice daily in combination with a change in dietary habits such as substituting acidic, spicy, fermented, sweet, fried foods and other foods with a high reflux potential as well as carbonated drinks and juices with the food with a low reflux potential and water significantly reduced the symptoms of LPR and increased the quality of life of the patients (p<0.001).
NOVELTY AND SCIENTIFIC CONTRIBUTION
This is the first study showing the correlation between dietary habits and the quality of life of patients with LPR. The contribution of this research is an objective assessment of the follow-up of patients with LPR that could be used in their regular assessment.
PubMed: 38205049
DOI: 10.17113/ftb.61.04.23.8222 -
Journal of Clinical Medicine Research Dec 2023The use of thromboelastography (TEG) has demonstrated decreased blood product utilization in patients with specific etiologies of major gastrointestinal bleeding (GIB),...
A Retrospective Study Comparing the Effect of Conventional Coagulation Parameters Vs. Thromboelastography-Guided Blood Product Utilization in Patients With Major Gastrointestinal Bleeding.
BACKGROUND
The use of thromboelastography (TEG) has demonstrated decreased blood product utilization in patients with specific etiologies of major gastrointestinal bleeding (GIB), such as variceal and non-variceal bleeding in cirrhosis patients; however, in a non-cirrhosis patient with GIB, there is far less evidence in the literature. Our retrospective study compares the effect of TEG-guided blood product utilization in patients with major GIB with all etiologies, including cirrhosis, admitted to medical intensive care unit (MICU).
METHODS
A retrospective chart review was conducted on patients admitted to the MICU of a tertiary academic medical center diagnosed with GIB using ICD-9/10 codes from 2014 to 2018. A total of 1,889 patients were identified, and validation criteria such as "GI or hepatology consult note", type and screen, pantoprazole, or octreotide drip" were used, which resulted in 997 patients, out of which 369 had a diagnosis of cirrhosis. Propensity score matching was done for baseline variables (age, sex, and race), ICU length of stay, hospital length of stay, ventilator days, and vasopressor use. As a result, 88 patients were included in the final analysis, with 44 in TEG and 44 in non-TEG group. A sub-group analysis was done in 46 patients with cirrhosis, 23 in TEG group and 23 in non-TEG group after propensity score matching.
RESULTS
There was significantly higher total blood volume (4,207 mL vs. 2,568 mL, P = 0.04) in the TEG group as compared to the non-TEG group, including total volume of cryoprecipitate (80 mL vs. 55 mL, P = 0.03) and total volume of platelet (543 mL vs. 327 mL, P = 0.03). In the cirrhosis sub-group, there was no significant difference in the amount of blood products transfused between the two groups.
CONCLUSION
This study revealed that TEG is not superior to conventional coagulation parameters in limiting the volume of blood product transfusion in major GIB patients in ICU settings.
PubMed: 38189039
DOI: 10.14740/jocmr5022 -
Pharmacology 2024Proton pump inhibitors (PPIs) are known to decrease the risk of gastrointestinal (GI) bleeding. However, concerns have been raised regarding the potential...
INTRODUCTION
Proton pump inhibitors (PPIs) are known to decrease the risk of gastrointestinal (GI) bleeding. However, concerns have been raised regarding the potential pharmacodynamic interactions of PPIs and antiplatelet drugs with respect to cardiovascular risk. Patients with BCR::ABL1-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), and polycythemia vera (PV) often suffer from peptic ulcer disease (PUD) and frequently receive low-dose aspirin due to an intrinsically high thrombotic risk.
METHOD
This retrospective multicenter study from a community setting investigated whether continuous PPI use may affect thrombohemorrhagic risk in ET and PV patients treated with long-term aspirin.
RESULTS
Ninety-four aspirin-treated MPN patients (ET = 36, PV = 58) were included; median age was 69.5 years (range 21-92) and 40 (42.6%) were males. Nineteen (20.2%) patients continuously received PPIs and pantoprazole (n = 15, 78.9%) was the most frequently received PPI. PV phenotype (p = 0.085), male sex (p = 0.011), and prior thrombosis (p = 0.005) were associated with PPI use, whereas no correlations were found with respect to age, disease risk, splenomegaly, mutational status, constitutional symptoms, cardiovascular risk factors, cytoreductive treatment, or any of the blood cell counts (p > 0.050 for all analyses). The median follow-up time was 55.5 months; 19 (20.2%) thrombotic and 13 (13.8%) bleeding events occurred during this time. The use of PPIs was not associated with an increased risk of thrombosis (p = 0.158) or overall bleeding (p = 0.229) and none of the patients treated with PPIs experienced GI bleeding.
CONCLUSIONS
Considering that Helicobacter pylori infection and PUD are quite frequent in ET and PV patients, these preliminary results may provide some reassurance to physicians regarding the absence of thrombohemorrhagic risk associated with prolonged PPI use in MPN patients treated with long-term aspirin. Our observations may be even more important in the light of recent evidence suggesting suboptimal platelet inhibition in ET with once-daily when compared to twice- or triple-daily aspirin which may also cause more abdominal discomfort. Limitations of this study are its retrospective design, limited number of patients included, and the lack of pharmacodynamic and pharmacokinetic assessments.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Young Adult; Aspirin; Helicobacter Infections; Helicobacter pylori; Hemorrhage; Pilot Projects; Polycythemia Vera; Proton Pump Inhibitors; Retrospective Studies; Thrombocythemia, Essential; Thrombosis
PubMed: 38171342
DOI: 10.1159/000535078 -
Archives of Pharmacal Research Jan 2024Pantoprazole is used to treat gastroesophageal reflux disease (GERD), maintain healing of erosive esophagitis (EE), and control symptoms related to Zollinger-Ellison...
Pantoprazole is used to treat gastroesophageal reflux disease (GERD), maintain healing of erosive esophagitis (EE), and control symptoms related to Zollinger-Ellison syndrome (ZES). Pantoprazole is mainly metabolized by cytochrome P450 (CYP) 2C19, converting to 4'-demethyl pantoprazole. CYP2C19 is a genetically polymorphic enzyme, and the genetic polymorphism affects the pharmacokinetics and/or pharmacodynamics of pantoprazole. In this study, we aimed to establish the physiologically based pharmacokinetic (PBPK) model to predict the pharmacokinetics of pantoprazole in populations with various CYP2C19 metabolic activities. A comprehensive investigation of previous reports and drug databases was conducted to collect the clinical pharmacogenomic data, physicochemical data, and disposition properties of pantoprazole, and the collected data were used for model establishment. The model was evaluated by comparing the predicted plasma concentration-time profiles and/or pharmacokinetic parameters (AUC and C) with the clinical observation results. The predicted plasma concentration-time profiles in different CYP2C19 phenotypes properly captured the observed profiles. All fold error values for AUC and C were included in the two-fold range. Consequently, the minimal PBPK model for pantoprazole related to CYP2C19 genetic polymorphism was properly established and it can predict the pharmacokinetics of pantoprazole in different CYP2C19 phenotypes. The present model can broaden the insight into the individualized pharmacotherapy for pantoprazole.
Topics: Cytochrome P-450 CYP2C19; Genotype; Pantoprazole; Phenotype; Polymorphism, Genetic; Humans
PubMed: 38150171
DOI: 10.1007/s12272-023-01478-7 -
Cureus Nov 2023N-butyl-2-cyanoacrylate (NB2CYA) is frequently used in the treatment of variceal hemorrhage with a success rate in hemostatic control of 87%-100%. Although rare,...
N-butyl-2-cyanoacrylate (NB2CYA) is frequently used in the treatment of variceal hemorrhage with a success rate in hemostatic control of 87%-100%. Although rare, complications include esophageal perforation, infection, or arterial and venous embolization. We present the case of a 67-year-old male with chronic ethanolic liver disease hospitalized due to melena and hematemesis. He had anemia requiring transfusion support, octreotide, and pantoprazole infusion. Upper digestive endoscopy was performed showing gastric varices with a hemorrhagic rupture point treated with cyanoacrylate. The patient developed respiratory failure over the next 48 hours with chest computed tomography (CT) angiography showing several dense, scattered linear images, with arterial vascular trajectories suggestive of cyanoacrylate embolization. It was decided to provide ventilatory support with invasive mechanical ventilation, initiate systemic corticosteroid therapy, and transfer the patient to the intensive care unit (ICU). The patient was ventilated for 11 days with initial favorable evolution, but after two episodes of decompensation of his chronic liver disease (CLD) (hepatic encephalopathy and hepatorenal syndrome) and a new nosocomial pneumonia, he ended up dying. The present case illustrates a rare but potentially fatal complication associated with cyanoacrylate, highlighting the importance of a high suspicion index in cases of respiratory failure and dyspnea after this therapy.
PubMed: 38143678
DOI: 10.7759/cureus.49329 -
Medical Oncology (Northwood, London,... Dec 2023Pantoprazole decreases the acidity of the tumor microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to... (Randomized Controlled Trial)
Randomized Controlled Trial
Pantoprazole decreases the acidity of the tumor microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to cytotoxic therapy. We conducted a phase I/II randomized controlled trial in adult patients with head and neck squamous cell carcinoma (HNSCC) planned for first-line palliative chemotherapy. Patients were randomized to chemotherapy + / - intravenous (IV) pantoprazole. The primary endpoint in phase I was to determine the maximum safe dose of intravenous pantoprazole, whereas it was progression-free survival (PFS) in phase II. The dose of IV pantoprazole established in phase I was 240 mg. Between Nov'18 and Oct'20, we recruited 120 patients in phase II, 59 on pantoprazole and 61 on the standard arm. Median age was 51 years (IQR 43-60), 80% were men. Systemic therapy was IV cisplatin in 22% and oral-metronomic-chemotherapy (OMC) in 78%. Addition of pantoprazole did not prolong PFS, which was 2.2 months (95% CI 2.07-3.19) in the pantoprazole arm and 2.5 months (95% CI 2.04-3.81, HR, 1.14; 95% CI 0.78-1.66; P = 0.48) in the standard arm. Response rates were similar; pantoprazole arm 8.5%, standard arm 6.6%; P = 0.175. Overall survival was also similar; 5.6 months (95% CI 4.47-8.51) in the pantoprazole arm and 5.4 months (95% CI 3.48-8.54, HR 1.06; 95% CI 0.72-1.57; P = 0.75) in the standard arm. Grade ≥ 3 toxicities were similar. Thus, pantoprazole 240 mg IV added to systemic therapy does not improve outcomes in patients with advanced HNSCC.
Topics: Adult; Male; Humans; Middle Aged; Female; Squamous Cell Carcinoma of Head and Neck; Pantoprazole; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Cisplatin; Antineoplastic Combined Chemotherapy Protocols; Tumor Microenvironment
PubMed: 38129716
DOI: 10.1007/s12032-023-02234-z -
European Journal of Drug Metabolism and... Jan 2024Although polypharmacy is a particular challenge in daily rheumatological practice, clinical research on the effects of hydroxychloroquine (HCQ), a commonly used drug for... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVE
Although polypharmacy is a particular challenge in daily rheumatological practice, clinical research on the effects of hydroxychloroquine (HCQ), a commonly used drug for patients with rheumatic diseases, is sparse on cytochrome P450 (CYP)-mediated metabolism. We have shown that pre-treatment with pantoprazole does not alter HCQ absorption in healthy volunteers. In this paper, we report the effects of a single 400 mg dose of HCQ on specific CYP3A and CYP2D6 substrates in healthy volunteers.
METHODS
In the trial, participants were randomized into two groups (HCQ plus a 9-day course of pantoprazole, or HCQ only). As a secondary endpoint, the effects of a single oral dose of HCQ on the exposure of the oral microdosed CYP3A probe drug midazolam (30 μg) and the oral microdosed CYP2D6 probe drug yohimbine (50 μg) were studied in 23 healthy volunteers (EudraCT no. 2020-001470-30, registered 31 March 2020).
RESULTS
The exposure of the probe drugs after intake of HCQ compared with baseline values was quantified by the partial area under the plasma concentration-time curve 0-6 h after administration (AUC) for yohimbine and the partial AUC for midazolam. Under HCQ, yohimbine AUC was unchanged, independent of CYP2D6 genotypes and pantoprazole exposure. Midazolam AUC was 25% higher on the day of HCQ administration than at baseline (p = 0.0007). This significant increase was driven by the pantoprazole subgroup, which showed a 46% elevation of midazolam AUC as compared with baseline (p < 0.0001). The ratio of midazolam to 1-OH-midazolam partial AUC significantly increased from 3.03 ± 1.59 (baseline) to 3.60 ± 1.56 (HCQ) in the pantoprazole group (p = 0.0026).
CONCLUSION
In conclusion, we observed an increased midazolam exposure most likely related to pantoprazole.
Topics: Humans; Area Under Curve; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Drug Interactions; Healthy Volunteers; Hydroxychloroquine; Midazolam; Pantoprazole; Pharmaceutical Preparations; Yohimbine
PubMed: 38114885
DOI: 10.1007/s13318-023-00872-2 -
Journal of Investigative Medicine High... 2023Acute esophageal necrosis (AEN) or black esophagus is a rare cause of mortality in patients with gastrointestinal bleeding. We present a case of a 54-year-old female who...
Acute esophageal necrosis (AEN) or black esophagus is a rare cause of mortality in patients with gastrointestinal bleeding. We present a case of a 54-year-old female who presented with diabetic ketoacidosis (DKA) and developed melena eventually attributed to AEN. The esophagogastroduodenoscopy (EGD) identified severe inflammation with black discoloration consistent with acute esophageal necrosis in the middle and lower esophagus. The patient was managed with intravenous pantoprazole and total parenteral nutrition (TPN) until she was able to tolerate an adequate diet. Black esophagus should be added to the differential diagnosis of patients with DKA who develop gastrointestinal bleeding. This need is stressed by the fact that early treatment is essential to reducing complications and mortality associated with the condition.
Topics: Female; Humans; Middle Aged; Diabetic Ketoacidosis; Acute Disease; Necrosis; Esophageal Diseases; Gastrointestinal Hemorrhage; Diabetes Mellitus
PubMed: 38097376
DOI: 10.1177/23247096231217852 -
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 -
Trials Dec 2023The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients.
OBJECTIVE
To outline the statistical analysis plan for the REVISE trial.
METHODS
REVISE is a randomized clinical trial ongoing in intensive care units (ICUs) internationally. Patients ≥ 18 years old, receiving invasive mechanical ventilation, and expected to remain ventilated beyond the calendar day after randomization are allocated to either 40 mg pantoprazole intravenously or placebo while mechanically ventilated.
RESULTS
The primary efficacy outcome is clinically important upper GI bleeding; the primary safety outcome is 90-day mortality. Secondary outcomes are ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine concentration, and duration of mechanical ventilation, ICU, and hospital length of stay. Following an interim analysis of results from 2400 patients (50% of 4800 target sample size), the data monitoring committee recommended continuing enrolment.
CONCLUSIONS
This statistical analysis plan outlines the statistical analyses of all outcomes, sensitivity analyses, and subgroup analyses. REVISE will inform clinical practice and guidelines worldwide.
TRIAL REGISTRATION
www.
CLINICALTRIALS
gov NCT03374800. November 21, 2017.
Topics: Adolescent; Humans; Critical Illness; Gastrointestinal Hemorrhage; Intensive Care Units; Pantoprazole; Pneumonia, Ventilator-Associated; Proton Pump Inhibitors; Respiration, Artificial; Adult
PubMed: 38057875
DOI: 10.1186/s13063-023-07794-z