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In Vivo (Athens, Greece) 2024Recent research has increasingly demonstrated an association between proton pump inhibitors (PPIs) and serious adverse events. This study aimed to evaluate the...
BACKGROUND/AIM
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.
PATIENTS AND METHODS
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.
RESULTS
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.
CONCLUSION
The findings suggest the need for vigilant monitoring of RM during PPI administration, particularly in the early stages, considering the varying onset times.
Topics: Humans; Proton Pump Inhibitors; Rhabdomyolysis; Male; Female; Pharmacovigilance; Middle Aged; Aged; Adult; Adverse Drug Reaction Reporting Systems; Databases, Factual; Aged, 80 and over; Young Adult; Adolescent; Esomeprazole
PubMed: 38688634
DOI: 10.21873/invivo.13567 -
Helicobacter 2024The systematic use of susceptibility testing and tailored first-line treatment for Helicobacter pylori eradication has yet to be established. (Randomized Controlled Trial)
Randomized Controlled Trial
14-day tailored PCR-guided triple therapy versus 14-day non-Bismuth concomitant quadruple therapy for Helicobacter pylori eradication: A multicenter, open-label randomized noninferiority controlled trial.
BACKGROUND
The systematic use of susceptibility testing and tailored first-line treatment for Helicobacter pylori eradication has yet to be established.
AIM
To compare 14-day tailored PCR-guided triple therapy to 14-day non-Bismuth concomitant quadruple therapy for first-line Helicobacter pylori eradication.
PATIENTS AND METHODS
We performed a multicenter, parallel-group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14-day tailored PCR-guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14-day non-Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication.
RESULTS
We screened 991 patients for eligibility and randomized 241 patients. The first-line eradication rate was 99.2% in the tailored PCR-guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at -0.68%). Both first-line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR-guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR-guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population.
CONCLUSION
In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14-day tailored PCR-guided triple therapy as a first-line H. pylori eradication therapy compared to 14-day non-Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236).
Topics: Humans; Helicobacter Infections; Male; Female; Middle Aged; Helicobacter pylori; Anti-Bacterial Agents; Drug Therapy, Combination; Adult; Clarithromycin; Polymerase Chain Reaction; Amoxicillin; Aged; Treatment Outcome; Metronidazole; Levofloxacin; Young Adult
PubMed: 38680067
DOI: 10.1111/hel.13076 -
Pharmaceuticals (Basel, Switzerland) Apr 2024[...].
Correction: Nasrullah et al. Omeprazole Prevents Colistin-Induced Nephrotoxicity in Rats: Emphasis on Oxidative Stress, Inflammation, Apoptosis and Colistin Accumulation in Kidneys. 2022, , 782.
[...].
PubMed: 38675505
DOI: 10.3390/ph17040540 -
Animals : An Open Access Journal From... Apr 2024The use of omeprazole as a preventive treatment for gastrointestinal ulcers in veterinary medicine has been questioned during previous years. The aim of the present...
The use of omeprazole as a preventive treatment for gastrointestinal ulcers in veterinary medicine has been questioned during previous years. The aim of the present study is to assess the long-term effect of omeprazole on cobalamin and serum gastrin levels in healthy dogs. Eighteen healthy dogs were included: 10 in the control group and 8 in the omeprazole group. Three samples were collected: before starting the treatment (T), 30 days after the start of treatment (T), and at 60 days (T). The mean cobalamin value (ng/L) in the control group was 481.4 (±293.70) at T, 481.4 (±170.21) at T, and 513.2 (±174.50) at T. In the omeprazole group, the values were 424.62 (±161.57) at T, 454.5 (±160.96) at T, and 414.87 (±127.90) at T. No statistically significant changes were detected in cobalamin levels between the three-time period in both study groups. These results agree with previous findings in felines but contrast with human medicine studies. The median gastrin values (pg/mL) in the control group were 62.45 [30.17-218.75] at T, 76.06 [30.67-199.87] at T, and 63.02 [35.81-176.06] at T. The median gastrin value in the omeprazole group was 67.59 [55.96-101.60] at T, 191.77 [75.31-1901.77] at T, and 128.16 [43.62-1066.46] at T. Statistically significant differences were detected ( = 0.008), indicating an increase in gastrin levels after initiating treatment with omeprazole. In conclusion, the increased levels of gastrin observed in this population underscore the importance of conducting a comprehensive clinical assessment to identify potential gastrointestinal disorders, particularly in consideration of the usage of omeprazole as a preventive treatment.
PubMed: 38672316
DOI: 10.3390/ani14081168 -
The Korean Journal of Gastroenterology... Apr 2024() is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND/AIMS
() is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have been used for eradication. We aimed to compare the efficacy of two different regimens as first-line eradication regimens, in an area with high antibiotic resistance.
METHODS
In this RCT, we assigned 223 patients with infection, who were naïve to treatment. They were randomly divided into two groups to receive either 12-day concomitant quadruple therapy (consisting of pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) or 14-day high dose dual therapy (consisting of esomeprazole 40 mg and amoxicillin 1 g TDS). eradication was assessed eight weeks after the end of treatment.
RESULTS
eradication rate by PP analysis for 12-day concomitant quadruple therapy and 14-day high dose dual therapy were 90.4% and 79.1%, respectively (p=0.02). According to ITT analysis, the eradication rates were 86.2% and 76.3%, respectively (p=0.06). Adverse drug reactions were 12.3% in high dose dual therapy and 36.8% in concomitant quadruple therapy (p<0.001).
CONCLUSIONS
Twelve-day concomitant therapy seems to be an acceptable regimen for first-line eradication in Iran, a country with a high rate of antibiotic resistance. Although, high dose dual therapy did not result in an ideal eradication rate, but it had fewer drug side effects than the 12-day concomitant regimen.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Administration Schedule; Drug Therapy, Combination; Esomeprazole; Helicobacter Infections; Helicobacter pylori; Metronidazole; Pantoprazole; Proton Pump Inhibitors; Treatment Outcome
PubMed: 38659251
DOI: 10.4166/kjg.2024.012 -
Antimicrobial Agents and Chemotherapy Apr 2024Currently, eradication by antibiotic therapy faces various challenges, including antibiotic resistance, side effects on intestinal commensal bacteria, and patient...
Currently, eradication by antibiotic therapy faces various challenges, including antibiotic resistance, side effects on intestinal commensal bacteria, and patient compliance. In this study, loureirin A (LrA), a traditional Chinese medicine monomer extracted from Sanguis Draconis flavones, was found to possess specific antibacterial activity against without the bacteria displaying a tendency to develop resistance . LrA demonstrated a synergistic or additive effect when combined with omeprazole (a proton pump inhibitor) against . The combination of LrA and omeprazole showed promising anti-. potential, exhibiting notable efficacy comparable to standard triple therapy in mouse models infected with both drug-sensitive and drug-resistant strains. Moreover, the narrow-spectrum antibacterial profile of LrA is reflected in its minimal effect on the diversity and composition of the mouse gut microbiota. The underlying mechanism of action of LrA against involves the generation of bactericidal levels of reactive oxygen species, resulting in apoptosis-like cell death. These findings indicate that LrA is a promising lead compound targeting without harming the commensal bacteria.
PubMed: 38656185
DOI: 10.1128/aac.00314-24 -
IScience May 2024Mounting evidence supports the role of neuroinflammation in radiation-induced brain injury (RIBI), a chronic disease characterized by delayed and progressive...
Mounting evidence supports the role of neuroinflammation in radiation-induced brain injury (RIBI), a chronic disease characterized by delayed and progressive neurological impairment. Asparagine endopeptidase (AEP), also known as legumain (LGMN), participates in multiple malignancies and neurodegenerative diseases and may potentially be involved in RIBI. Here, we found AEP expression was substantially elevated in the cortex and hippocampus of wild-type () mice following whole-brain irradiation. knockout () alleviated neurological impairment caused by whole-brain irradiation by suppressing neuronal senescence. Bulk RNA and metabolomic sequencing revealed AEP's involvement in the antigen processing and presentation pathway and neuroinflammation. This was further confirmed by co-culturing primary neurons with the conditioned media derived from irradiated or primary microglia. Furthermore, esomeprazole inhibited the enzymatic activity of AEP and RIBI. These findings identified AEP as a critical factor of neuroinflammation in RIBI, highlighting the prospect of targeting AEP as a therapeutic approach.
PubMed: 38655198
DOI: 10.1016/j.isci.2024.109698 -
Frontiers in Pediatrics 2024Gastrointestinal bleeding (GI) is a prevalent condition among pediatric patients, with a reported incidence of 6.4%, often severe enough to require admission to the...
INTRODUCTION
Gastrointestinal bleeding (GI) is a prevalent condition among pediatric patients, with a reported incidence of 6.4%, often severe enough to require admission to the pediatric intensive care unit (PICU). There are multiple therapies utilized in the management of GI bleeding in pediatrics, among which continuous intravenous (IV) infusion of omeprazole is used off-label without standard pediatric dosing recommendations. Reviewing the current literature reveals a lack of studies assessing the efficacy, safety, and appropriate dosing regimen of continuous omeprazole infusion in children with GI bleeding. This study aimed to evaluate the efficacy and safety of continuous IV omeprazole infusion in comparison to other therapeutic modalities in children.
METHODS
This study is a single-center, retrospective chart review of children admitted to the PICU at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. The treatment group included pediatric patients with GI bleeding and receiving omeprazole IV continuous infusion over ≥24 h while the control group included pediatric patients with GI bleeding managed using other therapies. Primary outcomes were the efficacy of omeprazole continuous infusion in stopping GI bleeding, and PICU length of stay (LOS). Secondary outcomes included instances of rebleeding post- therapy discontinuation, transfusion requirements, and the safety of omeprazole continuous infusion.
RESULTS
The study included 81 critically ill pediatric patients, 22 of whom received continuous infusion omeprazole while 59 received other therapies. The results indicated that patients in the control group had a significantly shorter PICU LOS (8 vs. 18.5 days, < 0.001) and bleeding episode (4 vs. 10.5 days, < 0.001) than those in the treatment group. However, no significant differences were observed between the two groups regarding secondary outcomes. The treatment group had a significantly lower all-cause mortality rate during hospitalization compared to the control group (16 patients [72.7%] vs. 56 patients [94.9%], respectively, = 0.005).
CONCLUSION
Empirical use of omeprazole continuous intravenous infusion in children with GI bleeding was not favorable in terms of shortening PICU LOS and duration of GI bleeding. Our study results provide evidence supporting the safety and tolerability of omeprazole continuous infusion. Additional larger studies are necessary to determine the implication of such results.
PubMed: 38650990
DOI: 10.3389/fped.2024.1270911 -
Frontiers in Allergy 2024Eosinophilic esophagitis is a newly recognized entity, in which there is significant evidence available that clearly demonstrates the positive impact of PPIs on reducing...
INTRODUCTION
Eosinophilic esophagitis is a newly recognized entity, in which there is significant evidence available that clearly demonstrates the positive impact of PPIs on reducing esophageal eosinophilia in individuals across different age groups, including children, adolescents, and adults. Multiple mechanisms have been proposed to explain how this treatment effect occurs. In Brazil, there seems to be a lack of studies that have prospectively assessed the clinical and therapeutic response rate in pediatric patients with EoE. The objective of this study was to prospectively evaluate the clinical and therapeutic response of pediatric patients with EoE in a medical center located in southern Brazil, by investigating the effectiveness of PPI treatment.
METHODS
This study is a clinical, prospective, open trial that took place in a pediatric hospital located in southern Brazil. The focus of the study was on patients diagnosed with Eosinophilic Esophagitis (EoE) who were given treatment using omeprazole/esomeprazole at a dosage of 1 mg.kg per dose, twice daily, for a period of 8-12 weeks. Following the treatment period, the patients underwent another endoscopy. Patients who exhibited 15 or less eosinophils in the biopsy conducted after the treatment were considered as responders.
RESULTS
A total of 27 patients was evaluated (74.1% boys). The average age (± standard deviation) was 8 years (±4). Nineteen patients (70.3%) were considered as responders to PPI treatment: 6 patients-22.2%-exhibited a complete response (defined as having 5 or fewer eosinophil per high power field. Additionally, 13 patients-48.1%-demonstrated a partial response, characterized by eosinophil counts exceeding 5 but less than 15 eos/hpf. When comparing the responder and non-responder groups at presentation, a statistical difference was observed in the prevalence of food refusal as a presenting symptom. Food refusal was found to be more prevalent in the non-responder group (87.5% vs. 26.3%, = 0.008). No differences were observed in terms of atopy history and endoscopic scores. Upon comparing the histological findings from the post-treatment endoscopy of the two groups, it was observed that PPI responders exhibited a greater tendency to decrease basal cell hyperplasia ( = 0.06) and intercellular edema ( = 0.08).
CONCLUSION
In this group of pediatric patients with EoE in Southern Brazil most patients showed a high prevalence of histological, endoscopic, and clinical response to PPI treatment. PPIs showed efficacy in Brazilian patients with EoE, most of whom would probably not be able to adequately undergo other treatments.
CLINICAL TRIAL REGISTRATION
https://ensaiosclinicos.gov.br/rg/RBR-2ntbth9, identifier (U1111-1301-1842).
PubMed: 38650863
DOI: 10.3389/falgy.2024.1346843 -
Biotechnic & Histochemistry : Official... Apr 2024The purpose of this study was to evaluate the effects of syringic acid, an anti-oxidant, on indomethacin induced gastric ulcers in rats. Experimental groups were...
The purpose of this study was to evaluate the effects of syringic acid, an anti-oxidant, on indomethacin induced gastric ulcers in rats. Experimental groups were control, ulcer, ulcer treated with 20 mg/kg esomeprazole (a proton pump inhibitor that reduces acid secretion), and ulcer treated with 100 mg/kg syringic acid. Rats were pretreated with esomeprazole or syringic acid two weeks before ulcer induction. Our histopathological observations showed that either syringic acid or esomeprazole attenuated the severity of gastric mucosal damage. Moreover, syringic acid and esomeprazole pretreatments alleviated indomethacin-induced damage by regulating oxidative stress, inflammatory response, the level of transforming growth factor-β (TGF-β), expressions of COX and prostaglandin E, cell proliferation, apoptosis and regulation of the NF-κB signaling pathway. We conclude that either esomeprazole or syringic acid administration protected the gastric mucosa from harmful effects of indomethacin. Syringic acid might, therefore be a potential therapeutic agent for preventing and treating indomethacin-induced gastric damage.
Topics: Animals; Indomethacin; Stomach Ulcer; Oxidative Stress; Apoptosis; Inflammation; Male; Gallic Acid; Rats; Rats, Sprague-Dawley; Gastric Mucosa; Esomeprazole
PubMed: 38644776
DOI: 10.1080/10520295.2024.2344477