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1.
Korean J Gastroenterol ; 83(4): 150-156, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38659251

RESUMO

Background/Aims: Helicobacter pylori (H. pylori) 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 H. pylori eradication. We aimed to compare the efficacy of two different regimens as first-line H. pylori eradication regimens, in an area with high antibiotic resistance. Methods: In this RCT, we assigned 223 patients with H. pylori 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). H. pylori eradication was assessed eight weeks after the end of treatment. Results: H. pylori 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 H. pylori 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.


Assuntos
Amoxicilina , Antibacterianos , Claritromicina , Quimioterapia Combinada , Esomeprazol , Infecções por Helicobacter , Helicobacter pylori , Metronidazol , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Claritromicina/administração & dosagem , Esquema de Medicação , Esomeprazol/uso terapêutico , Esomeprazol/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Metronidazol/uso terapêutico , Pantoprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Resultado do Tratamento
2.
Front Immunol ; 15: 1374611, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646544

RESUMO

Objectives: The aim of the study was to characterize the circulating immunome of patients with EoE before and after proton pump inhibitor (PPI) treatment in order to identify potential non-invasive biomarkers of treatment response. Methods: PBMCs from 19 healthy controls and 24 EoE patients were studied using a 39-plex spectral cytometry panel. The plasmacytoid dendritic cell (pDC) population was differentially characterized by spectral cytometry analysis and immunofluorescence assays in esophageal biopsies from 7 healthy controls and 13 EoE patients. Results: Interestingly, EoE patients at baseline had lower levels of circulating pDC compared with controls. Before treatment, patients with EoE who responded to PPI therapy had higher levels of circulating pDC and classical monocytes, compared with non-responders. Moreover, following PPI therapy pDC levels were increased in all EoE patients, while normal levels were only restored in PPI-responding patients. Finally, circulating pDC levels inversely correlated with peak eosinophil count and pDC count in esophageal biopsies. The number of tissue pDCs significantly increased during active EoE, being even higher in non-responder patients when compared to responder patients pre-PPI. pDC levels decreased after PPI intake, being further restored almost to control levels in responder patients post-PPI. Conclusions: We hereby describe a unique immune fingerprint of EoE patients at diagnosis. Moreover, circulating pDC may be also used as a novel non-invasive biomarker to predict subsequent response to PPI treatment.


Assuntos
Biomarcadores , Células Dendríticas , Esofagite Eosinofílica , Inibidores da Bomba de Prótons , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/imunologia , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/sangue , Masculino , Feminino , Adulto , Biomarcadores/sangue , Células Dendríticas/imunologia , Pessoa de Meia-Idade , Eosinófilos/imunologia , Resultado do Tratamento , Adulto Jovem , Biópsia , Estudos de Casos e Controles
3.
Expert Opin Drug Metab Toxicol ; 20(4): 225-233, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38600865

RESUMO

INTRODUCTION: Cyclin-dependent kinase (CDK) 4/6 inhibitors are cornerstones in the treatment of Hormone Receptor (HR) positive and Human Epidermal Growth factor (HER2) negative metastatic breast cancer. Given their widespread use in the metastatic setting and emerging use in the adjuvant setting, studying drug-drug interactions (DDI) of these medications is of utmost importance. AREAS COVERED: This review provides key background information on the CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib. We discuss drug-drug interactions including those with proton pump inhibitors as well as CYP3A substrates, inhibitors, and inducers. We describe the effect of these drugs on membrane transporters and their substrates as well as those drugs that increase risk of CDK4/6 toxicities. Finally, we explore future directions for strategies to minimize drug-drug interactions. EXPERT OPINION: It is crucial to be mindful of medications that may interfere with drug absorption, such as proton pump inhibitors, as well as those that interfere with drug metabolism, such as CYP3A4 inhibitors and inducers. Additionally, special consideration should be given to populations at higher risk for polypharmacy, such as older patients with greater comorbidities. These interactions and patient characteristics should be considered when developing individual treatment plans with CDK4/6 inhibitors.


Assuntos
Neoplasias da Mama , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Interações Medicamentosas , Inibidores de Proteínas Quinases , Humanos , Neoplasias da Mama/tratamento farmacológico , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Feminino , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/farmacocinética , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/farmacologia , Inibidores da Bomba de Prótons/efeitos adversos , Aminopiridinas/administração & dosagem , Aminopiridinas/efeitos adversos , Aminopiridinas/farmacologia , Benzimidazóis/administração & dosagem , Benzimidazóis/farmacologia , Benzimidazóis/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridinas/farmacologia , Piridinas/farmacocinética
4.
World J Gastroenterol ; 30(10): 1280-1286, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38596495

RESUMO

Yu et al's study in the World Journal of Gastroenterology (2023) introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii (S. boulardii) for the rescue therapy against Helicobacter pylori (H. pylori), a pathogen responsible for peptic ulcers and gastric cancer. Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression, which is minimally affected by mealtime. Compared to proton pump inhibitors, which bind irreversibly to cysteine residues in the H+/K+-ATPase pump, Vonoprazan competes with the K+ ions, prevents the ions from binding to the pump and blocks acid secretion. Concerns with increasing antibiotic resistance, effects on the gut microbiota, patient compliance, and side effects have led to the advent of a dual regimen for H. pylori. Previous studies suggested that S. boulardii plays a role in stabilizing the gut barrier which improves H. pylori eradication rate. With an acceptable safety profile, the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile, thereby strengthening the applicability in clinical settings. Nonetheless, S. boulardii comes in various formulations and dosages, warranting further exploration into the optimal dosage for supplementation in rescue therapy. Additionally, larger, randomized, double-blinded controlled trials are warranted to confirm these promising results.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Pirróis , Saccharomyces boulardii , Sulfonamidas , Humanos , Amoxicilina/uso terapêutico , Antibacterianos/efeitos adversos , Infecções por Helicobacter/tratamento farmacológico , Claritromicina/uso terapêutico , Quimioterapia Combinada , Inibidores da Bomba de Prótons/efeitos adversos , ATPase Trocadora de Hidrogênio-Potássio , Íons/farmacologia , Íons/uso terapêutico , Resultado do Tratamento
5.
World J Gastroenterol ; 30(9): 1213-1223, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38577188

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) infects over half the global population, causing gastrointestinal diseases like dyspepsia, gastritis, duodenitis, peptic ulcers, G-MALT lymphoma, and gastric adenocarcinoma. Eradicating H. pylori is crucial for treating and preventing these conditions. While conventional proton pump inhibitor (PPI)-based triple therapy is effective, there's growing interest in longer acid suppression therapies. Potassium competitive acid blocker (P-CAB) triple and dual therapy are new regimens for H. pylori eradication. Initially used in Asian populations, vonoprazan (VPZ) has been recently Food and Drug Administration-approved for H. pylori eradication. AIM: To assess the efficacy of regimens containing P-CABs in eradicating H. pylori infection. METHODS: This study, following PRISMA 2020 guidelines, conducted a systematic review and meta-analysis by searching MEDLINE and Scopus libraries for randomized clinical trials (RCTs) or observational studies with the following command: [("Helicobacter pylori" OR "H pylori") AND ("Treatment" OR "Therapy" OR "Eradication") AND ("Vonaprazan" OR "Potassium-Competitive Acid Blocker" OR "P-CAB" OR "PCAB" OR "Revaprazan" OR "Linaprazan" OR "Soraprazan" OR "Tegoprazan")]. Studies comparing the efficacy of P-CABs-based treatment to classical PPIs in eradicating H. pylori were included. Exclusion criteria included case reports, case series, unpublished trials, or conference abstracts. Data variables encompassed age, diagnosis method, sample sizes, study duration, intervention and control, and H. pylori eradication method were gathered by two independent reviewers. Meta-analysis was performed in R software, and forest plots were generated. RESULTS: A total of 256 references were initially retrieved through the search command. Ultimately, fifteen studies (7 RCTs, 7 retrospective observational studies, and 1 comparative unique study) were included, comparing P-CAB triple therapy to PPI triple therapy. The intention-to-treat analysis involved 8049 patients, with 4471 in the P-CAB intervention group and 3578 in the PPI control group across these studies. The analysis revealed a significant difference in H. pylori eradication between VPZ triple therapy and PPI triple therapy in both RCTs and observational studies [risk ratio (RR) = 1.17, 95% confidence interval (CI): 1.11-1.22, P < 0.0001] and (RR = 1.13, 95%CI: 1.09-1.17, P < 0.0001], respectively. However, no significant difference was found between tegoprazan (TPZ) triple therapy and PPI triple therapy in both RCTs and observational studies (RR = 1.04, 95%CI: 0.93-1.16, P = 0.5) and (RR = 1.03, 95%CI: 0.97-1.10, P = 0.3), respectively. CONCLUSION: VPZ-based triple therapy outperformed conventional PPI-based triple therapy in eradicating H. pylori, positioning it as a highly effective first-line regimen. Additionally, TPZ-based triple therapy was non-inferior to classical PPI triple therapy.


Assuntos
Derivados de Benzeno , Infecções por Helicobacter , Helicobacter pylori , Imidazóis , Sulfonamidas , Humanos , Antibacterianos/farmacologia , Claritromicina/uso terapêutico , Inibidores da Bomba de Prótons/efeitos adversos , Quimioterapia Combinada , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/etiologia , Pirróis/uso terapêutico , Amoxicilina/uso terapêutico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Observacionais como Assunto
6.
J Immunother Cancer ; 12(3)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38458634

RESUMO

BACKGROUND: While concomitant medications can affect the efficacy of immune checkpoint inhibitors (ICIs), few studies have assessed associations of concomitant medications with the occurrence and profile of immune-related adverse events (irAEs). METHODS: This study assessed associations of concomitant medication (antibiotics/proton pump inhibitors (PPIs)/corticosteroids)-based risk model termed the "drug score" with survival and the occurrence and profile of irAEs in 851 patients with advanced cancer treated with ICIs (with or without other agents). The study also assessed the survival impact of the occurrence of irAEs, using a landmark analysis to minimize immortal time bias. Multivariable Cox proportional hazard analyses were conducted for progression-free survival (PFS) and overall survival (OS). RESULTS: The drug score classified patients into three risk groups, with significantly different PFS and OS. Notably, the score's predictive capability was better in patients treated with ICIs only than in those treated with ICIs plus other agents. The landmark analysis showed that patients who developed irAEs had significantly longer PFS and OS than those without irAEs. Generally, concomitant medications were negatively associated with the occurrence of irAEs, especially endocrine irAEs, whereas PPI use was positively associated with gastrointestinal irAEs, as an exception. CONCLUSIONS: Using a large pan-cancer cohort, the prognostic ability of the drug score was validated, as well as that of the occurrence of irAEs. The negative association between concomitant medications and irAE occurrence could be an indirect measure of the detrimental effect on the immune system induced by one or more concomitant drugs.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias/tratamento farmacológico , Antibacterianos , Intervalo Livre de Progressão , Inibidores da Bomba de Prótons
7.
Chirurgia (Bucur) ; 119(1): 36-43, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38465714

RESUMO

AIM: Clostridium difficile infection is a cause of increased morbidity and mortality in hospitals, particularly in patients with cancer pathology. There are several factors favouring the development of Clostridium difficile infection among cancer patients, including age, exposure to antibiotic and proton pump inhibitors therapy, and chemotherapy. This study was conducted to observe the prevalence of Clostridium difficile infection after the reversal of ileostomy loop for rectal cancer surgery, which were initially operated either open or laparoscopic. METHOD: A retrospective study was performed on patients who were operated in a single surgical team for rectal cancer who benefited of a diverted loop ileostomy over a 4-year period. Results: 23 patients were documented with Clostridium difficile infection out of a total of 63. All 23 patients underwent ileostomy closure later than 3 months after primary surgery, and postoperatively received antibiotic therapy associated with proton pump inhibitors in the first 24 hours. Conclusions: Closure of ileostomy later than 3 months after primary surgery, combined with chemotherapy, antibiotic therapy and proton pump inhibitors, increases the risk of developing Clostridium difficile infection.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Neoplasias Retais , Humanos , Ileostomia/efeitos adversos , Estudos Retrospectivos , Inibidores da Bomba de Prótons , Resultado do Tratamento , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/etiologia , Neoplasias Retais/cirurgia , Neoplasias Retais/complicações , Antibacterianos/uso terapêutico
8.
Aliment Pharmacol Ther ; 59(9): 1062-1081, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38517201

RESUMO

BACKGROUND: Acute upper gastrointestinal bleeding (UGIB) is a common emergency requiring hospital-based care. Advances in care across pre-endoscopic, endoscopic and post-endoscopic phases have led to improvements in clinical outcomes. AIMS: To provide a detailed, evidence-based update on major aspects of care across pre-endoscopic, endoscopic and post-endoscopic phases. METHODS: We performed a structured bibliographic database search for each topic. If a recent high-quality meta-analysis was not available, we performed a meta-analysis with random effects methods and odds ratios with 95% confidence intervals. RESULTS: Pre-endoscopic management of UGIB includes risk stratification, a restrictive red blood cell transfusion policy unless the patient has cardiovascular disease, and pharmacologic therapy with erythromycin and a proton pump inhibitor. Patients with cirrhosis should be treated with prophylactic antibiotics and vasoactive medications. Tranexamic acid should not be used. Endoscopic management of UGIB depends on the aetiology. For peptic ulcer disease (PUD) with high-risk stigmata, endoscopic therapy, including over-the-scope clips (OTSCs) and TC-325 powder spray, should be performed. For variceal bleeding, treatment should be customised by severity and anatomic location. Post-endoscopic management includes early enteral feeding for all UGIB patients. For high-risk PUD, PPI should be continued for 72 h, and rebleeding should initially be evaluated with a repeat endoscopy. For variceal bleeding, high-risk patients or those with further bleeding, a transjugular intrahepatic portosystemic shunt can be considered. CONCLUSIONS: Management of acute UGIB should include treatment plans for pre-endoscopic, endoscopic and post-endoscopic phases of care, and customise treatment decisions based on aetiology and severity of bleeding.


Assuntos
Varizes Esofágicas e Gástricas , Úlcera Péptica , Humanos , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Varizes Esofágicas e Gástricas/tratamento farmacológico , Endoscopia Gastrointestinal , Inibidores da Bomba de Prótons/uso terapêutico
9.
Intern Med ; 63(5): 649-657, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38432892

RESUMO

A 90-year-old man on maintenance hemodialysis was admitted due to severe symptomatic anemia. Biopsies under esophagogastroduodenoscopy demonstrated that the cause of anemia was intermittent blood oozing from multiple gastric hyperplastic polyps. Even after successful eradication of Helicobacter pylori, he showed hypergastrinemia (480 pg/mL) owing to esomeprazole (proton-pump inhibitor) therapy for the past 4.5 years to treat reflux esophagitis. Seven months after we switched esomeprazole to famotidine (H2-receptor antagonist), those gastric polyps and anemia were remarkably ameliorated with lowered gastrin levels. This case indicates that long-term use of a proton-pump inhibitor triggers chronic hypergastrinemia, leading to gastric hyperplastic polyps and subsequent severe anemia.


Assuntos
Anemia , Inibidores da Bomba de Prótons , Masculino , Humanos , Idoso de 80 Anos ou mais , Inibidores da Bomba de Prótons/efeitos adversos , Esomeprazol/efeitos adversos , Anemia/induzido quimicamente , Biópsia , Hiperplasia/induzido quimicamente , Diálise Renal/efeitos adversos
10.
J Extracell Vesicles ; 13(4): e12426, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38532609

RESUMO

Besides participating in diverse pathological and physiological processes, extracellular vesicles (EVs) are also excellent drug-delivery vehicles. However, clinical drugs modulating EV levels are still lacking. Here, we show that proton pump inhibitors (PPIs) reduce EVs by enhancing macropinocytosis-mediated EV uptake. PPIs accelerate intestinal cell endocytosis of autocrine immunosuppressive EVs through macropinocytosis, thereby aggravating inflammatory bowel disease. PPI-induced macropinocytosis facilitates the clearance of immunosuppressive EVs from tumour cells, improving antitumor immunity. PPI-induced macropinocytosis also increases doxorubicin and antisense oligonucleotides of microRNA-155 delivery efficiency by EVs, leading to enhanced therapeutic effects of drug-loaded EVs on tumours and acute liver failure. Mechanistically, PPIs reduce cytosolic pH, promote ATP6V1A (v-ATPase subunit) disassembly from the vacuolar membrane and enhance the assembly of plasma membrane v-ATPases, thereby inducing macropinocytosis. Altogether, our results reveal a mechanism for macropinocytic regulation and PPIs as potential modulators of EV levels, thus regulating their functions.


Assuntos
Vesículas Extracelulares , Inibidores da Bomba de Prótons , Endocitose , Pinocitose , Adenosina Trifosfatases
11.
Surg Endosc ; 38(4): 2180-2187, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38448622

RESUMO

BACKGROUND AND AIMS: Anti-reflux mucosectomy with cap-assisted endoscopic mucosal resection (ARMS-C) is a safe and effective treatment for managing refractory gastroesophageal reflux disease (GERD). This study aimed to investigate the short and long-term outcomes of ARMS-C. METHODS: This study was conducted from 2018 to 2022, during which 115 eligible patients underwent ARMS-C. The primary endpoints of this study were to evaluate the GERD-Q questionnaire score and determine the number of patients who reduced their proton pump inhibitor (PPI) dosage or discontinued PPI usage. The secondary endpoints included the evaluation of the DeMeester score, acid exposure time (AET), gastroesophageal flap valve grade (GEFV), lower esophageal sphincter pressure, the rate of successful esophageal peristalsis, and GERD-Q questionnaires. Additionally, we analyzed the long-term efficacy of ARMS-C. RESULTS: Out of the 120 patients, 115 underwent ARMS-C, 96 were followed up for at least six months after the procedure, and 22 were followed up for at least two years. The primary outcome showed a significant improvement in GERD-Q scores, decreasing from 10.67 to 7.55 (p < 0.001). Out of the 96 patients, 36 were able to reduce or completely stop using PPIs. The DeMeester score, GEFV, AET, and the proportion of intact peristalsis also demonstrated improvement. As for the long-term efficacy of ARMS-C, 86% of patients showed improvement in symptoms, and no serious adverse effects were reported after the procedure. CONCLUSION: ARMS-C is a safe and effective endoscopic technique to treat refractory GERD patients.


Assuntos
Ressecção Endoscópica de Mucosa , Refluxo Gastroesofágico , Humanos , Ressecção Endoscópica de Mucosa/efeitos adversos , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/cirurgia , Refluxo Gastroesofágico/complicações , Resultado do Tratamento , Tempo , Inquéritos e Questionários , Inibidores da Bomba de Prótons/uso terapêutico
12.
Anal Biochem ; 689: 115501, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38453048

RESUMO

Vonoprazan and amoxicillin are pharmacological combinations that demonstrate synergistic effects in treating Helicobacter pylori (H. pylori), a global public health concern associated with peptic ulcer disease and gastric cancer. Four spectrophotometric methods were developed, including two univariate techniques (Fourier self-deconvolution and ratio difference) and two multivariate chemometric approaches (partial least squares and principal component regression). These methods provide innovative solutions for effectively resolving and accurately quantifying the overlapping spectra of vonoprazan and amoxicillin. The concentration ranges covered were 3-60 µg ml-1 for vonoprazan and 5-140 µg ml-1 for amoxicillin. To assess the environmental sustainability of the methodologies, various measures such as the Green Analytical Procedure Index (GAPI), National Environmental Method Index (NEMI), Analytical GREEnness Calculator, and Analytical Eco-scale, as well as RGB12 and hexagon toll were implemented. The validation of the developed techniques was carried out in compliance with ICH standards. The present study is highly significant because it is the first time that the mixture has been determined using the current approaches. The comparative analysis demonstrated no significant difference in terms of accuracy and precision compared to reference HPLC method (p = 0.05). The established spectrophotometric methods offer a straightforward, rapid, and cost-effective alternative to complex analytical techniques for determining the vonoprazan and amoxicillin mixture. They show potential for routine analysis in research laboratories and pharmaceutical industries.


Assuntos
Amoxicilina , Infecções por Helicobacter , Sulfonamidas , Humanos , Amoxicilina/uso terapêutico , Antibacterianos , Claritromicina/uso terapêutico , Metronidazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Quimioterapia Combinada , Estudos Retrospectivos , Pirróis
13.
BMC Gastroenterol ; 24(1): 110, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491413

RESUMO

BACKGROUND: Both vonoprazan and proton pump inhibitors (PPIs) are currently used to treat artificial ulcers after gastric endoscopic submucosal dissection. However, evidence-based medicine proving the efficacy of vonoprazan is still lacking. Therefore, this meta-analysis aimed to compare the efficacy of vonoprazan and PPIs for the treatment of artificial ulcers after gastric endoscopic submucosal dissection. METHODS: The PubMed, EMBASE and Cochrane Library databases were searched up to September 2023 for related randomized controlled trials (RCTs). RCTs that compared the efficacy of vonoprazan and PPIs in treating artificial gastric ulcers after gastric endoscopic submucosal dissection were included. Two independent reviewers screened the included studies, extracted the data and assessed the risk of bias. The following outcomes were extracted for comparison: ulcer healing rate, ulcer shrinkage rate, delayed postoperative bleeding rate, and ulcer perforation rate. RESULTS: Nine randomized controlled trials involving 926 patients were included. The pooled results showed that vonoprazan had a significantly lower rate of delayed postoperative bleeding than did PPIs (RR = 0.46; 95% CI = 0.23-0.91; P = 0.03). No significant differences were found in terms of ulcer healing, shrinkage rates, or ulcer perforation rates between vonoprazan and PPIs. CONCLUSIONS: Compared with PPIs, vonoprazan is superior at reducing delayed postoperative bleeding after endoscopic submucosal dissection. However, further studies are needed to prove the efficacy of vonoprazan. SYSTEMATIC REVIEW REGISTRATION: Identifier CRD42024509227.


Assuntos
Ressecção Endoscópica de Mucosa , Pirróis , Neoplasias Gástricas , Úlcera Gástrica , Sulfonamidas , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/etiologia , Úlcera Gástrica/cirurgia , Úlcera/tratamento farmacológico , Úlcera/etiologia , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Neoplasias Gástricas/cirurgia , Hemorragia Pós-Operatória , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Cell Biochem Funct ; 42(2): e3967, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38480622

RESUMO

A drug interaction is a condition in which two or more drugs are taken at the same time. Type 2 diabetes mellitus is a significant contributor to polypharmacy. Proton pump inhibitors (PPIs) are often prescribed in combination with metformin or DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin, and alogliptin) or a combined dose of metformin and DPP-4 inhibitor to treat gastritis in diabetic patients. This review article mainly focused on evaluating the potential drug-drug interactions (DDIs) between PPIs (i.e. esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole) with metformin and PPIs with DPP-4 inhibitors. The findings demonstrated the existence of pharmacokinetic and pharmacodynamic DDIs between the aforementioned PPIs with metformin and DPP-4 inhibitors, which could impact the biological activities (i.e., hypoglycemia) of these drugs. Moreover, this review suggested that esomeprazole could be the best drug in the PPI group to be prescribed simultaneously with metformin and DPP-4 inhibitors, as most of the antidiabetic drugs of this study did not show any interaction with esomeprazole. The findings of this study also revealed that both antidiabetic drugs and PPIs could have positive interactions as PPIs have the potential to lessen the gastrointestinal side effects of metformin and DPP-4 inhibitors. To achieve the greatest therapeutic impact with the fewest side effects, careful dose control of these drugs is required. So, more extensive research on both human and animal subjects are needed to ascertain the veracity of this hypothesis.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Metformina , Animais , Humanos , Inibidores da Bomba de Prótons/farmacocinética , Inibidores da Dipeptidil Peptidase IV/farmacologia , Esomeprazol/farmacologia , Metformina/farmacologia , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Interações Medicamentosas
15.
Drugs Aging ; 41(2): 141-151, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38340290

RESUMO

Helicobacter pylori is the main etiopathogenetic factor of chronic gastritis, peptic ulcer disease and gastric cancer. The world's population is shifting towards older people, who have the highest prevalence of H. pylori. Aging-related peculiarities could have an impact on the treatment of H. pylori and there is still a lack of research data in the older population. The aim of this review was to summarize the findings of the most recent information, publications and studies on the issues relating to H. pylori infection in older patients. H. pylori eradication offers gastrointestinal and extra gastrointestinal benefits in older patients. Based on the main guidelines, H. pylori should be eradicated independent of the patient's age, only reconsidering cases with terminal illness and low life expectancy. Proton pump inhibitors are generally safe and well tolerated. Some antibiotics require dose adjustment only in advanced renal insufficiency and the risk of hepatotoxicity is very low. Special precautions should be taken in patients with polypharmacy and those taking aspirin or non-steroidal anti-inflammatory drugs. In older patients, H. pylori eradication treatment frequently causes only mild and short-term adverse events; however, treatment compliance is usually still very good. H. pylori treatment in older patients does not increase the risk of Clostridium difficile infection. Optimal eradication effectiveness (> 90%) is mostly achieved with bismuth- and non-bismuth-based quadruple therapies. Susceptibility-guided treatment of H. pylori can contribute to increasing the effectiveness of eradication regimens in older adults. To achieve optimal H. pylori eradication effectiveness in older patients, the same guidelines, which are applied to adults, also apply to this population: avoiding repetitive treatment prescriptions, choosing quadruple therapies, prescribing longer treatment duration and administering high-dose proton pump inhibitors twice daily.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Idoso , Inibidores da Bomba de Prótons/efeitos adversos , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/induzido quimicamente , Antibacterianos/efeitos adversos , Bismuto/efeitos adversos , Quimioterapia Combinada , Resultado do Tratamento
17.
Drugs ; 84(3): 319-327, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38388872

RESUMO

Treatment for the eradication of Helicobacter pylori infection, a leading cause of peptic ulcer disease and an important risk factor for gastric cancer and mucosa-associated lymphoid tissue lymphoma, is indicated whenever infection is identified. However, treatment success rates with current guideline-recommended proton-pump inhibitor (PPI)-based regimens remain suboptimal, with one potential factor associated with treatment failure being inadequate acid suppression. Vonoprazan (Voquezna®) is a first-in-class potassium-competitive acid blocker with the potential to provide potent and sustained acid suppression. Following clinical trials conducted mainly in Asia (supported by post-marketing experience from Asia) and the phase III PHALCON-HP trial conducted in the USA and Europe, vonoprazan is now approved in the USA for use in combination with amoxicillin (dual therapy) or amoxicillin and clarithromycin (triple therapy) for the treatment of H. pylori infection in adults. The vonoprazan-based dual and triple therapy regimens were generally well tolerated in PHALCON-HP. In addition, vonoprazan has advantages including a rapid onset of action and no food effect, making vonoprazan-based dual and triple therapy regimens valuable alternatives to standard PPI-based triple therapy in the treatment of H. pylori infection.


Infection with the bacterium Helicobacter pylori is a leading cause of peptic ulcer disease and has been identified as an important risk factor for gastric cancer. Current recommended treatments for H. pylori infection generally involve a combination of antibiotics together with an acid suppressant, such as a proton-pump inhibitor (PPI). However, treatment success rates with current guideline-recommended PPI-based regimens remain suboptimal. Vonoprazan (Voquezna®), from a new class of drugs known as potassium-competitive acid blockers, has the potential to provide potent and sustained acid suppression. Based on the findings of a pivotal trial (PHALCON-HP) conducted in the USA and Europe, vonoprazan is now approved in the USA for the treatment of H. pylori infection in adults when used in combination with amoxicillin, or amoxicillin and clarithromycin. Alongside the demonstrated efficacy and tolerability of the vonoprazan-based regimens, vonoprazan has a rapid onset of action and can be taken with or without food. Thus, vonoprazan-based dual and triple therapy regimens present valuable alternatives to standard PPI-based triple therapy in the treatment of H. pylori infection.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Sulfonamidas , Adulto , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/induzido quimicamente , Antibacterianos/efeitos adversos , Quimioterapia Combinada , Amoxicilina/farmacologia , Amoxicilina/uso terapêutico , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Pirróis/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos , Resultado do Tratamento
18.
Gut Liver ; 18(2): 257-264, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38384180

RESUMO

Background/Aims: : Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases. This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers. Methods: : Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed. Results: : One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups. Conclusions: : Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.


Assuntos
Derivados de Benzeno , Ressecção Endoscópica de Mucosa , Imidazóis , Neoplasias Gástricas , Úlcera Gástrica , Humanos , Esomeprazol/uso terapêutico , Úlcera/tratamento farmacológico , Úlcera/etiologia , Inibidores da Bomba de Prótons/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/cirurgia , Úlcera Gástrica/etiologia , Neoplasias Gástricas/etiologia , Ressecção Endoscópica de Mucosa/efeitos adversos
19.
Curr Gastroenterol Rep ; 26(4): 93-98, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38393432

RESUMO

PURPOSE OF REVIEW: Gastroesophageal reflux disease (GERD) is very common in the general population and poses a large societal socio-economic burden. In this article, we review the evidence supporting non-ablative radiofrequency treatment (Stretta) for the endoscopic management of GERD and we compare it to pharmacologic and other minimally invasive and surgical interventions. RECENT FINDINGS: Proton pump inhibitors (PPI) are a key therapy for GERD. For patients without associated significant sliding hiatal hernia, who have inadequate relief of their reflux symptoms, Stretta and other endoscopic therapies, such as transoral fundoplication (TIF), may improve symptoms and GERD-related quality of life. Unfortunately, there are no recent large randomized controlled trials, and most of the evidence is based on meta-analyses and small scale, prospective and retrospective single center efforts. Comparisons of Stretta efficacy to other anti-reflux endoscopic modalities and anti-reflux surgery (ARS) are also presented. There are several endoscopic and minimally invasive modalities to manage PPI-refractory GERD acting through various mechanisms that have been found effective in managing GERD symptoms and quality of life. Among them, Stretta has the longest track record of efficacy and safety. Larger-scale and longer-term comparative efficacy trials in selected populations of patients with acid reflux with and without hiatal hernia will be needed.


Assuntos
Refluxo Gastroesofágico , Laparoscopia , Humanos , Qualidade de Vida , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Refluxo Gastroesofágico/cirurgia , Refluxo Gastroesofágico/diagnóstico , Fundoplicatura/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico
20.
Biol Pharm Bull ; 47(2): 518-526, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38403662

RESUMO

To investigate the risk of acute kidney injury (AKI) in patients with cancer following the initiation of proton pump inhibitors (PPIs) and potassium-competitive acid blocker (PCAB), considering sex and anti-cancer drug use. We conducted a self-controlled case-series study using the Japan Medical Data Center claims data from 12422 patients with cancer who were prescribed PPIs or PCAB between January 2017 and December 2019. Considering the timing of PPI or PCAB, control period (days -120 to -1), risk period 1 (days 0 to +30), and risk period 2 (days +31 to +365) were defined. To assess the incidence rate ratio (IRR) and 95% confidence interval (CI) as the risk ratio, we adjusted for anti-cancer drugs to assess the risk of AKI. Additionally, we also examined sex differences to identify the risk of AKI. AKI was observed in risk period 1 [2.05 (1.12-3.72), p = 0.0192], but a slight reduction was noted in risk period 2 [0.60 (0.36-1.00), p = 0.0481]. A sex-specific increase in the risk of AKI was observed only in males during risk period 1 [2.18 (1.10-4.32), p = 0.0260], with a reduction in risk period 2 [0.48 (0.26-0.89), p = 0.0200]. We identified an increased risk of AKI in patients with cancer starting PPIs or PCAB particularly in males within 30 d after PPI or PCAB initiation, emphasizing the need for vigilant monitoring and management of AKI in this patient population.


Assuntos
Injúria Renal Aguda , Neoplasias , Humanos , Masculino , Feminino , Inibidores da Bomba de Prótons/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Incidência , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Bases de Dados Factuais , Fatores de Risco , Estudos Retrospectivos
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