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1.
Phytomedicine ; 88: 153584, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34119741

RESUMO

BACKGROUND: Proton pump inhibitors (PPIs) play an important role in the treatment of nonerosive reflux disease (NERD), but their long-term and excessive uses have been associated with safety concerns. Chinese herbal medicine (CHM) has become a popular alternative treatment for this condition. METHODS: A total of 204 patients were randomly assigned to the combination group or PPI group (1:1 ratio). They were given JianpiQinghua (JQ) granules (34.8 g) plus omeprazole (10 mg) plus dummy omeprazole (10 mg) or dummy JQ granules (34.8 g) plus omeprazole (20 mg) daily for 4 weeks. The primary endpoints were the rate of sufficient relief and complete resolution of GERD Q at week 4. Metabonomics and the gut microbiota were also assessed. RESULTS: Complete resolution was observed in 40.8% of patients in the combination group and 26.8% of patients in the PPI group after 4 weeks (FAS analysis, OR, 1.88; 95% CI, 1.03-3.44; p = 0.039). Sufficient relief was observed in 50% of patients in the combination group and 43.30% of patients in the PPI group after 4 weeks (FAS analysis, OR, 1.31; 95% CI, 0.74-2.30; p = 0.35). Three patients had liver dysfunction, one of whom had a mild case and 2 of whom had moderate-to-severe cases in the combination group. Patients in the combination group showed a significant increase in richness and diversity of their gut microbiota compared with those in the PPI group. Metabonomics showed that the combination therapy could correct the glutamate metabolism pathway. CONCLUSION: Our findings demonstrate the superior efficacy of JQ granules combined with omeprazole (10 mg) vs. omeprazole (20 mg) in terms of symptom relief in patients with NERD. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02892357. Registered on 14 February 2019.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Omeprazol/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Terapias Complementares , Método Duplo-Cego , Feminino , Refluxo Gastroesofágico/etiologia , Fármacos Gastrointestinais/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Omeprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Resultado do Tratamento
2.
Clin Transl Gastroenterol ; 12(4): e00341, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33988530

RESUMO

INTRODUCTION: Current guidelines recommend intravenous (IV) proton pump inhibitor (PPI) therapy in peptic ulcer bleeding (PUB). We aimed to compare the efficacy of oral and IV administration of PPIs in PUB. METHODS: We performed a systematic search in 4 databases for randomized controlled trials, which compared the outcomes of oral PPI therapy with IV PPI therapy for PUB. The primary outcomes were 30-day recurrent bleeding and 30-day mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes, while weighted mean differences (WMDs) with CI were calculated for continuous outcomes in meta-analysis. The protocol was registered a priori onto PROSPERO (CRD42020155852). RESULTS: A total of 14 randomized controlled trials reported 1,951 peptic ulcer patients, 977 and 974 of which were in the control and intervention groups, respectively. There were no statistically significant differences between oral and IV administration regarding 30-day rebleeding rate (OR = 0.96, CI: 0.65-1.44); 30-day mortality (OR = 0.70, CI: 0.35-1.40); length of hospital stay (WMD = -0.25, CI: -0.93 to -0.42); transfusion requirements (WMD = -0.09, CI: -0.07 to 0.24); need for surgery (OR = 0.91, CI: 0.40-2.07); further endoscopic therapy (OR = 1.04, CI: 0.56-1.93); and need for re-endoscopy (OR = 0.81, CI: 0.52-1.28). Heterogeneity was negligible in all analysis, except for the analysis on the length of hospitalization (I2 = 82.3%, P = 0.001). DISCUSSION: Recent evidence suggests that the oral administration of PPI is not inferior to the IV PPI treatment in PUB after endoscopic management, but further studies are warranted.


Assuntos
Úlcera Péptica Hemorrágica/tratamento farmacológico , Inibidores da Bomba de Prótons/administração & dosagem , Administração Intravenosa , Administração Oral , Transfusão de Sangue , Endoscopia Gastrointestinal , Estudos de Equivalência como Asunto , Humanos , Tempo de Internação , Úlcera Péptica Hemorrágica/mortalidade , Úlcera Péptica Hemorrágica/cirurgia , Prevenção Secundária , Resultado do Tratamento
3.
Medicine (Baltimore) ; 100(20): e25420, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011021

RESUMO

ABSTRACT: This retrospective study investigated the preventive effect of intravenous esomeprazole (IVEO) in the prevention of nonvarices upper gastrointestinal bleeding (NUGIB).This study enrolled 130 patients with NUGIB and all of them underwent successful endoscopic hemostasis, of which 65 cases received routine management and IVEO (Group A) and the other 65 cases received routine management alone (Group B). The primary outcome (recurrent bleeding rate within 72-hour, 7-day, and 30-day), and secondary outcomes ((all-cause mortality, bleeding-related mortality, blood transfused, hospital stay (day), and incidence of adverse events)) were compared between 2 groups.Patients in the group A showed lower recurrent bleeding rate within 72-hour(P < .05), 7-day (P < .05), and 30-day (P < .05), than that of patients in the group B. However, no significant differences were identified in all-cause mortality(P = .26), bleeding-related mortality (P = .57), blood transfused (P = .33), and hospital stay (P = .74) between 2 groups. In addition, both groups had similar safety profile.This study found that routine management and IVEO was superior to the routine management alone for preventing the recurrent bleeding rate after successful endoscopic hemostasis in patients with NUGIB.


Assuntos
Esomeprazol/administração & dosagem , Hemostase Endoscópica/estatística & dados numéricos , Úlcera Péptica Hemorrágica/terapia , Inibidores da Bomba de Prótons/administração & dosagem , Prevenção Secundária/métodos , Adolescente , Adulto , Idoso , Transfusão de Sangue/estatística & dados numéricos , Terapia Combinada/métodos , Terapia Combinada/estatística & dados numéricos , Feminino , Mortalidade Hospitalar , Humanos , Infusões Intravenosas/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica Hemorrágica/mortalidade , Recidiva , Estudos Retrospectivos , Prevenção Secundária/estatística & dados numéricos , Resultado do Tratamento , Adulto Jovem
4.
Isr Med Assoc J ; 23(4): 245-250, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33899358

RESUMO

BACKGROUND: Hypomagnesemia (serum magnesium level < 1.7 mg/dl) occurs more frequently in patients with type 2 diabetes mellitus (T2DM).Serum magnesium levels are not routinely tested in hospitalized patients, including in hospitalized patients with T2DM. OBJECTIVES: To evaluate the prevalence of hypomagnesemia among hospitalized T2DM patients treated with proton pump inhibitors (PPIs) and/or diuretics. METHODS: A total of 263 T2DM patients hospitalized in general departments were included in the study and were further divided into four groups: group 1 (patients not treated with PPIs or diuretics), group 2 (patients treated with PPIs), group 3 (patients treated with diuretics), and group 4 (patients treated with both PPIs and diuretics).  Blood and urine samples were taken during the first 24 hours of admission. Electrocardiogram was performed on admission. RESULTS: Of the 263 T2DM patients, 58 (22.1%) had hypomagnesemia (serum magnesium level < 1.7 mg/dl). Patients in group 2 had the lowest mean serum magnesium level (1.79 mg/dl ± 0.27). Relatively more patients with hypomagnesemia were found in group 2 compared to the other groups, although a statistically significant difference was not observed. Significantly more patients in group 3 and 4 had chronic renal failure. Patients with hypomagnesemia had significantly lower serum calcium levels. CONCLUSIONS: Hospitalized T2DM patients under PPI therapy are at risk for hypomagnesemia and hypocalcemia.


Assuntos
Cálcio/sangue , Diabetes Mellitus Tipo 2 , Falência Renal Crônica , Magnésio/sangue , Doenças Metabólicas , Idoso , Comorbidade , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diuréticos/administração & dosagem , Diuréticos/efeitos adversos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Israel/epidemiologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Pessoa de Meia-Idade , Prevalência , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos
5.
Medicine (Baltimore) ; 100(14): e25136, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832076

RESUMO

BACKGROUND: Proton pump inhibitors (PPIs) decrease the rate of rebleeding following endoscopic hemostatic therapy in patients with bleeding peptic ulcers. This study compares the efficacy of oral omeprazole vs intravenous omeprazole in decrease of rebleeding of peptic ulcer patients. METHOD: The present study was authorized by the local research ethics committee of Jiangjin District Central Hospital (2020120987) and informed consent was obtained from all patients. All adult patients who were admitted to medical emergency rooms of Jiangjin District Central Hospital due to upper gastrointestinal bleeding (as evidenced by hematemesis, melena or hematochezia) were considered for inclusion in the study. Endoscopy was performed within 24 hours after admission. Patients older than 18 years with successful endoscopic therapy of high risk ulcers [defined as active bleeding (Forrest IA, IB), non-bleeding visible vessel (NBVV, Forrest IIA) or adherent clots (Forrest IIB)] were enrolled. Patients with low risk ulcers (clean base, ulcers with a simple washable clot), suspicious malignant ulcer, bleeding tendency, uremia, liver cirrhosis, Mallory Weiss tear or already on PPI as an outpatient were excluded from study. All were managed endoscopically by injecting 5-30 ml of epinephrine (diluted 1:10000) around the ulcer crater. Cavitations or flattening of bleeding vessel and disappearance of NBVV was considered as established homeostasis. A biopsy was taken from antrum for evaluating Helicobacter pylori infection. Patient with unsuccessful endoscopic therapy were not enrolled and were referred to general surgeon. Information on demography, history of previous upper gastrointestinal bleeding, NSAID or ASA ingestion, ulcer location, bleeding stigmata and blood transfusion volume at entry were recorded in all patients. In the oral omeprazole group, the patients received 40 mg omeprazole orally twice daily for 72 hours. In intravenous omeprazole group, they received omeprazole 80 mg bolus and then 8 mg/hour infusion for 48-72 hours. Then, all patients received omeprazole 20 mg orally for 30 days. On the day of discharge Helicobacter pylori infected patients received standard regimens. RESULTS: Figure 1 showed the primary and secondary end points. DISCUSSION: Intravenous administration of PPIs has limitations. They are expensive, require a dedicated intravenous line, need nursing supervision and hospital admission. So, it would be reasonable to prescribe oral PPIs to patients with high risk bleeding ulcers provided that it is as effective as its intravenous counterpart. Oral PPIs have a high bioavailability. Its effect initiates one hour after ingestion and the maximal plasma concentration is achieved after 2-3 hours. However, there are few studies comparing oral and intravenous PPI in decreasing risk of rebleeding in peptic ulcer patients. More high quality randomized controlled trials are still necessary. REGISTRATION NUMBER: researchregistry 6588.


Assuntos
Omeprazol/administração & dosagem , Úlcera Péptica Hemorrágica/tratamento farmacológico , Úlcera Péptica/complicações , Inibidores da Bomba de Prótons/administração & dosagem , Administração Intravenosa , Administração Oral , Adulto , Humanos , Úlcera Péptica Hemorrágica/etiologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Am J Gastroenterol ; 116(5): 899-917, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33929377

RESUMO

We performed systematic reviews addressing predefined clinical questions to develop recommendations with the GRADE approach regarding management of patients with overt upper gastrointestinal bleeding. We suggest risk assessment in the emergency department to identify very-low-risk patients (e.g., Glasgow-Blatchford score = 0-1) who may be discharged with outpatient follow-up. For patients hospitalized with upper gastrointestinal bleeding, we suggest red blood cell transfusion at a threshold of 7 g/dL. Erythromycin infusion is suggested before endoscopy, and endoscopy is suggested within 24 hours after presentation. Endoscopic therapy is recommended for ulcers with active spurting or oozing and for nonbleeding visible vessels. Endoscopic therapy with bipolar electrocoagulation, heater probe, and absolute ethanol injection is recommended, and low- to very-low-quality evidence also supports clips, argon plasma coagulation, and soft monopolar electrocoagulation; hemostatic powder spray TC-325 is suggested for actively bleeding ulcers and over-the-scope clips for recurrent ulcer bleeding after previous successful hemostasis. After endoscopic hemostasis, high-dose proton pump inhibitor therapy is recommended continuously or intermittently for 3 days, followed by twice-daily oral proton pump inhibitor for the first 2 weeks of therapy after endoscopy. Repeat endoscopy is suggested for recurrent bleeding, and if endoscopic therapy fails, transcatheter embolization is suggested.


Assuntos
Úlcera Péptica Hemorrágica/terapia , Trato Gastrointestinal Superior , Eletrocoagulação , Embolização Terapêutica , Endoscopia Gastrointestinal , Transfusão de Eritrócitos , Hemostasia Cirúrgica , Humanos , Gravidade do Paciente , Inibidores da Bomba de Prótons/administração & dosagem , Fatores de Risco
7.
Medicine (Baltimore) ; 100(8): e24808, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33663099

RESUMO

BACKGROUND: Previous studies have showed that anti-acid therapy with proton pump inhibitors (PPIs) can inhibit pancreatic secretion and it may be used in treating acute pancreatitis (AP). But at present, there is no systematic reviews for the evidence and the therapeutic effectiveness and safety of anti-acid therapy with PPIs in AP were not unclear. Therefore, we will undertake a systematic review of the literature to summarize previous evidence regarding this topic, in order to clarify the effectiveness and safety of anti-acid therapy with PPIs in AP. METHODS: We will search the EMBASE, WANFANG DATA, Web of Knowledge, China National Knowledge Infrastructure, PubMed, ClinicalTrials.gov and Cochrane Library from inception to June 30,2021 to retrieve relevant studies using the search strategy: ("Proton pump inhibitors" OR "PPI" OR "PPIs" OR "Omeprazole" OR "Tenatoprazole" OR "Pantoprazole" OR "acid suppression therapy" OR "acid suppression drugs") AND ("pancreatitis" OR "pancreatitides"). Two authors independently judged study eligibility and extracted data. Heterogeneity will be examined by computing the Q statistic and I2 statistic. RESULTS: This study assessed the efficiency and safety of proton pump inhibitors for treating acute pancreatitis. CONCLUSIONS: This study will provide reliable evidence-based evidence for the clinical application of PPIs for treating AP. ETHICS AND DISSEMINATION: Ethical approval is unnecessary as this protocol is only for systematic review and does not involve privacy data. The findings of this study will be disseminated electronically through a peer-review publication or presented at a relevant conference.


Assuntos
Pancreatite/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , Humanos , Omeprazol/uso terapêutico , Pantoprazol/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Projetos de Pesquisa
8.
Medicine (Baltimore) ; 100(6): e24366, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578533

RESUMO

BACKGROUND: Pharmacokinetic and pharmacodynamic study showed a lower clopidogrel response when coprescribed with proton pump inhibitors (PPIs). Despite this, PPIs is necessary for patients treated with long term dual antiplatelet therapy (DAPT). Ethnic variance also played a different effect on clopidogrel response. Our study evaluated the effect of concomitant use of DAPT and PPIs and assessed whether ethnic variance exert different effect on clinical outcomes. METHODS: We carefully searched EMBASE, PubMed/Medline databases, and the Cochrane library in April 2019. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE) and individual endpoints reported. We also focused on bleeding events. Studies were excluded if the follow-up were <12 months and patients were not treated with clopidogrel after stent implantation. RESULTS: A total of 18 studies were included in the systematic review (involving 79,670 patients). No randomized controlled trials (RCTs) were included. PPIs comedication were associated with increased MACCE (odds ratio [OR] = 1.38; 95% confidence interval [CI] = 1.28-1.49) while not associated with decreased bleeding risks, such as gastrointestinal bleeding (OR = 1.05; 95% CI = 0.53-2.11). PPIs comedication were associated with increased risk for all endpoints among Caucasian population while not with increased risk for MACE (OR = 1.20; 95% CI = 0.99-1.39), all-cause death (OR = 1.24; 95% CI = 0.74-2.06), cardiac-death (OR = 1.29; 95% CI = 0.64-2.57) among Asian population. CONCLUSION: PPIs comedication were associated with adverse clinical outcomes, and ethnic variance may exert different effect on clinical outcomes. Subgroup analysis indicated that concomitant use of PPI might be suitable for Asian patients after stent implantation.


Assuntos
Implante de Prótese Vascular , Prótese Vascular , Clopidogrel/uso terapêutico , Grupos de Populações Continentais , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Stents , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/métodos , Clopidogrel/administração & dosagem , Grupos de Populações Continentais/estatística & dados numéricos , Oclusão Coronária/prevenção & controle , Oclusão Coronária/terapia , Quimioterapia Combinada , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Resultado do Tratamento
9.
Life Sci ; 271: 119155, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33548286

RESUMO

Acute kidney injury (AKI) is a progressive renal complication which significantly affects the patient's life with huge economic burden. Untreated acute kidney injury eventually progresses to a chronic form and end-stage renal disease. Although significant breakthroughs have been made in recent years, there are still no effective pharmacological therapies for the treatment of acute kidney injury. Toll-like receptor 4 (TLR4) is a well-characterized pattern recognition receptor, and increasing evidence has shown that TLR4 mediated inflammatory response plays a pivotal role in the pathogenesis of acute kidney injury. The expression of TLR4 has been seen in resident renal cells, including podocytes, mesangial cells, tubular epithelial cells and endothelial cells. Activation of TLR4 signaling regulates the transcription of numerous pro-inflammatory cytokines and chemokines, resulting in renal inflammation. Therefore, targeting TLR4 and its downstream effectors could serve as an effective therapeutic intervention to prevent renal inflammation and subsequent kidney damage. For the first time, this review summarizes the literature on acute kidney injury from the perspective of TLR4 from year 2010 to 2020. In the current review, the role of TLR4 signaling pathway in AKI with preclinical evidence is discussed. Furthermore, we have highlighted several compounds of natural and synthetic origin, which have the potential to avert the renal TLR4 signaling in preclinical AKI models and have shown protection against AKI. This scientific review provides new ideas for targeting TLR4 in the treatment of AKI and provides strategies for the drug development against AKI.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Receptor 4 Toll-Like/metabolismo , Injúria Renal Aguda/imunologia , Animais , Sistemas de Liberação de Medicamentos/tendências , Medicamentos de Ervas Chinesas/administração & dosagem , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Células Endoteliais/metabolismo , Glucocorticoides/administração & dosagem , Humanos , Inibidores da Bomba de Prótons/administração & dosagem , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/imunologia
10.
Expert Rev Clin Pharmacol ; 14(3): 399-404, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33576287

RESUMO

Background: : Proton pump inhibitors (PPI) are associated with Clostridium difficile infection (CDI). Impact of the route of administration is unknown.Research Design and Methods: Patients in Multiparameter Intelligent Monitoring in Intensive Care II database (MIMIC-II) from 2001 to 2008, >18 years old, admitted to medical, surgical, or cardiac ICUs were included. PPI exposures were omeprazole, esomeprazole, lansoprazole, and pantoprazole. PPI administration routes were oral or intravenous. Patients who received histamine receptor antagonists (H2RA) were the control arm. CDI was identified using ICD-9 diagnostic code 008.45. Multiple logistic regression analysis was performed to calculate odds ratios (OR).Results: The study included 16,820 patients (57% male) with a mean age of 63 (SD±17) years and hospitalization duration of 10.2 days (SD±11). Pantoprazole was the most common PPI (94%). CDI occurred in 2.4% and more in patients receiving PPIs than H2RAs (3.0% vs. 0.8%, p < 0.001). CDI prevalence increased with intravenous (95%CI = 1.69-3.39, OR 2.4) and oral (95%CI = 1.59-3.27, OR 2.3) PPI use compared to H2RAs. CDI prevalence was not associated with PPI route in the multivariable model (OR 1.07, 95%CI 0.86-1.34).Conclusions: Both intravenous and oral PPI use in the ICU were independently associated with CDI.


Assuntos
Infecções por Clostridium/epidemiologia , Infecção Hospitalar/epidemiologia , Unidades de Terapia Intensiva , Inibidores da Bomba de Prótons/efeitos adversos , Administração Intravenosa , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Infecção Hospitalar/microbiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prevalência , Inibidores da Bomba de Prótons/administração & dosagem , Estudos Retrospectivos
11.
J Vasc Interv Radiol ; 32(4): 569-575, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33461872

RESUMO

PURPOSE: To investigate the association between the use of proton pump inhibitors (PPIs) and the risk of early biliary infection (EBI) after the placement of percutaneous transhepatic biliary stents (PTBS) in patients with unresectable malignant biliary obstruction (MBO). MATERIALS AND METHODS: A total of 136 patients with unresectable MBO (82 males and 54 females) treated with PTBS were included in this multicenter retrospective study. PPIs were prescribed to MBO patients with dyspepsia. The risk factors for EBI were identified by univariate and multivariate analyses. The association between the use of PPIs and EBI was assessed by logistic analyses. RESULTS: A total of 72 (53%) patients were regular users of PPIs, and 33 (24%) patients developed EBI after PTBS. Univariate and multivariate analyses revealed that diabetes (hazard ratio [HR], 20.3; 95% confidence interval [CI], 5.6-72.9; P <.001), biliary stones (HR, 20.3; 95% CI, 5.6-72.9; P <.001) and PPIs (HR, 4.0; 95% CI, 1.2-12.8; P =.020) were risk factors for EBI. Further analyses of the correlation between the duration of PPIs use and EBI demonstrated that a prolonged use of PPIs significantly increased the risk of EBI (PPIs for <15 days vs 15-30 days: HR, 10.2; 95% CI, 3.1-33.3; P <.001; and PPIs <15 days vs ≥30 days; HR, 20.4; 95% CI, 2.2-192.3; P <.001). CONCLUSION: The use of PPIs increased the risk of EBI after PTBS in patients with unresectable MBO. Furthermore, the risk of EBI increased with a prolonged duration of PPIs use.


Assuntos
Infecções Bacterianas/microbiologia , Bile/microbiologia , Cateterismo/instrumentação , Colestase/terapia , Neoplasias/complicações , Inibidores da Bomba de Prótons/efeitos adversos , Stents , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/diagnóstico , Cateterismo/efeitos adversos , China , Colestase/diagnóstico por imagem , Colestase/etiologia , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/administração & dosagem , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
12.
Biomed Pharmacother ; 136: 111251, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33450486

RESUMO

BACKGROUND: Although proton pump inhibitors (PPIs) are widely used in the prevention of gastric bleeding caused by endoscopic submucosal dissection (ESD), there is no consensus on the optimal regimen for these patients. Therefore, we aim to investigate whether intermittent use of low-dose PPI is sufficient to prevent post-ESD bleeding. METHODS: This multicenter, non-inferiority, randomized controlled trial was conducted at 9 hospitals in China. Consecutive eligible patients with a diagnosis of gastric mucosal lesions after ESD treatment were randomly assigned (1:1) to receive either intermittent low-dose or continuous high-dose PPIs treatment. After three days, all patients administered orally esomeprazole 40 mg once a day for 8 weeks. The primary endpoint was post-ESD bleeding within 7 days. Analysis was done according to the intention-to-treat principle with the non-inferiority margin (Δ) of 5%. RESULTS: 526 consecutive patients were assessed for eligibility from 30 September 2017 to 30 July 2019, of whom 414 were randomly assigned to low-dose (n = 209) or high-dose (n = 205) esomeprazole treatment group without dropouts within7 days. The total post-ESD bleeding is occurred in 13 (6.2 %, 95 % CI 3.3-9.6) of 209 within 7 days in the intermittent low-dose group, and 12 (5.9 %, 95 % CI 2.9-9.3) of 205 in the continuous high-dose group. The absolute risk reduction (ARR) was 0.4 % (-4.2, 4.9). One month after ESD, There are 44 patients (21.1 %, 95 % CI 15.8, 26.8) and 39 patients (19.0 % 95 % CI 13.7, 24.4) in scar stage respectively in low-dose group and high-dose group (P = 0.875).The hospital costs in the low-dose PPI group was lower than high -dose group (P = 0.005). CONCLUSION: The intermittent use of low-dose PPIs is sufficient to prevent post-ESD bleeding. It might be applied in clinical practice to prevent post-ESD bleeding and reduce the costs related to PPIs.


Assuntos
Ressecção Endoscópica de Mucosa/efeitos adversos , Esomeprazol/administração & dosagem , Hemorragia Pós-Operatória/prevenção & controle , Inibidores da Bomba de Prótons/administração & dosagem , Estômago/cirurgia , Idoso , China , Esomeprazol/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/etiologia , Inibidores da Bomba de Prótons/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
13.
Clin Transl Gastroenterol ; 12(1): e00294, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33448708

RESUMO

INTRODUCTION: To define the best cutoff of the Glasgow-Blatchford score (GBS) for identifying high- and low-risk rebleeding patients with bleeding ulcers and high-risk stigmata after endoscopic hemostasis and compare the efficacy of high-dose and standard-dose intravenous proton pump inhibitors (HD-IVPs and SD-IVPs, respectively) in this patient population. METHODS: We retrospectively reviewed the data of 346 patients with bleeding ulcers and high-risk stigmata who underwent endoscopic hemostasis between March 2014 and September 2018 in our center and were divided into an HD-IVP group and an SD-IVP group. Propensity score-matching analysis was performed to control for selection bias and other potential confounders. Recurrent bleeding rates were calculated according to the GBS. RESULTS: Overall, 346 patients meeting the inclusion criteria were enrolled, with 89 patients in the SD-IVP group and 89 patients in the HD-IVP group after matching with all baseline characteristics balanced (P > 0.05). GBS = 8 was the best cutoff for identifying high-risk rebleeding patients (GBS ≥ 8) with a significant difference (P = 0.015) in recurrence rate between the SD-IVP (17/61, 27.9%) and HD-IVP (7/65, 10.8%) groups and low-risk rebleeding patients (GBS < 8) with no difference (P = 1) in recurrence rate between the SD-IVP (2/28, 7.1%) and HD-IVP (2/24, 8.3%) groups. DISCUSSION: The best cutoff for identifying high-risk and low-risk rebleeding patients with bleeding ulcers and high-risk stigmata after endoscopic hemostasis was GBS = 8. Although HD-IVP is more effective than SD-IVP in high-risk patients, they are equally effective in low-risk patients.


Assuntos
Hemostase Endoscópica , Úlcera Péptica Hemorrágica/tratamento farmacológico , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Idoso , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Úlcera Péptica Hemorrágica/sangue , Úlcera Péptica Hemorrágica/terapia , Pontuação de Propensão , Recidiva , Estudos Retrospectivos , Fatores de Risco , Prevenção Secundária , Resultado do Tratamento
14.
BMJ ; 372: m4903, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414239

RESUMO

OBJECTIVE: To assess the use of proton pump inhibitors (PPIs) to treat persistent throat symptoms. DESIGN: Pragmatic, double blind, placebo controlled, randomised trial. SETTING: Eight ear, nose, and throat outpatient clinics, United Kingdom. PARTICIPANTS: 346 patients aged 18 years or older with persistent throat symptoms who were randomised according to recruiting centre and baseline severity of symptoms (mild or severe): 172 to lansoprazole and 174 to placebo. INTERVENTION: Random blinded allocation (1:1) to either 30 mg lansoprazole twice daily or matched placebo twice daily for 16 weeks. MAIN OUTCOME MEASURES: Primary outcome was symptomatic response at 16 weeks measured using the total reflux symptom index (RSI) score. Secondary outcomes included symptom response at 12 months, quality of life, and throat appearances. RESULTS: Of 1427 patients initially screened for eligibility, 346 were recruited. The mean age of the study sample was 52.2 (SD 13.7) years, 196 (57%) were women, and 162 (47%) had severe symptoms at presentation; these characteristics were balanced across treatment arms. The primary analysis was performed on 220 patients who completed the primary outcome measure within a window of 14-20 weeks. Mean RSI scores were similar between treatment arms at baseline: lansoprazole 22.0 (95% confidence interval 20.4 to 23.6) and placebo 21.7 (20.5 to 23.0). Improvements (reduction in RSI score) were observed in both groups-score at 16 weeks: lansoprazole 17.4 (15.5 to19.4) and placebo 15.6 (13.8 to 17.3). No statistically significant difference was found between the treatment arms: estimated difference 1.9 points (95% confidence interval -0.3 to 4.2 points; P=0.096) adjusted for site and baseline symptom severity. Lansoprazole showed no benefits over placebo for any secondary outcome measure, including RSI scores at 12 months: lansoprazole 16.0 (13.6 to 18.4) and placebo 13.6 (11.7 to 15.5): estimated difference 2.4 points (-0.6 to 5.4 points). CONCLUSIONS: No evidence was found of benefit from PPI treatment in patients with persistent throat symptoms. RSI scores were similar between the lansoprazole and placebo groups after 16 weeks of treatment and at the 12 month follow-up. TRIAL REGISTRATION: ISRCTN Registry ISRCTN38578686 and EudraCT 2013-004249-17.


Assuntos
Lansoprazol/administração & dosagem , Faringite/tratamento farmacológico , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Esofagite Péptica/complicações , Feminino , Refluxo Gastroesofágico/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Faringite/etiologia , Qualidade de Vida , Reino Unido
15.
Isr Med Assoc J ; 23(1): 38-42, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33443341

RESUMO

BACKGROUND: The antibiotic resistance profile of Helicobacter pylori (H. pylori) is constantly changing. Up-to-date and reliable data for the effectiveness of first-line H. pylori treatment protocols are necessary to provide evidence-based best-practice guidelines. OBJECTIVES: To determine the effectiveness, compliance and safety of first-line treatment for H. pylori in Israel. METHODS: An observational, prospective, multicenter study was conducted in tertiary referral centers in Israel, as part of the European registry on H. pylori management (Hp-EuReg). H. pylori-infected patients were included from 2013 to March 2020. Data collected included demographics, clinical data, diagnostic tests, previous eradication attempts, current treatment, compliance, adverse events, and treatment outcome result. RESULTS: In total, 242 patients were registered, including 121 (50%) who received first-line therapy, 41% of these individuals received clarithromycin based triple therapy and 58.9% received a four-drug regimen. The overall effectiveness of first-line therapy was 85% and 86% by modified intention-to-treat and per protocol analyses, respectively. The effectiveness of both sequential and concomitant therapies was 100% while clarithromycin-based triple therapy achieved an eradication rate of 79%. Treatment eradication was higher among patients who received high dose proton pump inhibitor (PPI) compared to those treated with low dose PPI (100% vs. 81.5% respectively, P < 0.01). No difference in treatment effectiveness was found between 7-, 10-, and 14-day treatment. CONCLUSIONS: The effectiveness of clarithromycin-based triple therapy is suboptimal. First-line treatment of H. pylori infection should consist of four drugs, including high dose PPI, according to international guidelines.


Assuntos
Antibacterianos , Claritromicina/administração & dosagem , Infecções por Helicobacter , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , Antibacterianos/administração & dosagem , Antibacterianos/classificação , Relação Dose-Resposta a Droga , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Humanos , Israel/epidemiologia , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Retratamento/métodos , Retratamento/estatística & dados numéricos , Resultado do Tratamento
16.
Rheumatology (Oxford) ; 60(2): 849-854, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32829395

RESUMO

OBJECTIVE: To investigate the association between proton pump inhibitor (PPI) use and the presence and severity of calcinosis in SSc. METHODS: We analysed data from two SSc cohorts from a single centre. Cohort 1 included 199 patients reviewed over 10 years, for whom retrospective data on PPI use and calcinosis were available. Cohort 2 was recruited prospectively and included 215 consecutive patients, who underwent clinical assessment. Outcomes of interest were presence of current calcinosis (CC) or calcinosis at any time (CAT). RESULTS: The cohort 1 data analysis showed that among patients on standard dose PPI 20% had calcinosis, while in those on high doses of PPI calcinosis was present in 39% (P = 0.003). Analysis of the data from cohort 2 confirmed these findings, demonstrating that the odds of CAT increased significantly with longer PPI exposure [odds ratio (OR) 1.04, 95% CI: 1.02, 1.06; P < 0.001], longer disease duration (OR 1.08, 95% CI: 1.05, 1.12; P < 0.001) and greater age (OR 1.03, CI: 1.01, 1.05; P = 0.010). Multivariable logistic regression showed that higher exposure to PPI remained a significant predictor of calcinosis, with PPI exposure >10 years increasing the risk of CAT >6-fold, compared with no PPI (OR 6.37, 95% CI: 1.92, 21.17; P = 0.003) after adjusting for disease duration and antibodies. CONCLUSION: We confirm a significant association between high PPI exposure with severity of calcinosis in SSc. Given the clinical impact of calcinosis and reflux in SSc, PPI exposure as a potentially modifiable risk factor for calcinosis requires further evaluation.


Assuntos
Calcinose , Refluxo Gastroesofágico/tratamento farmacológico , Efeitos Adversos de Longa Duração , Inibidores da Bomba de Prótons , Escleroderma Sistêmico , Fatores Etários , Calcinose/diagnóstico , Calcinose/epidemiologia , Calcinose/etiologia , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Refluxo Gastroesofágico/etiologia , Humanos , Efeitos Adversos de Longa Duração/diagnóstico , Efeitos Adversos de Longa Duração/epidemiologia , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Medição de Risco/estatística & dados numéricos , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/fisiopatologia , Índice de Gravidade de Doença , Reino Unido/epidemiologia
17.
Am J Epidemiol ; 190(1): 142-149, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-32596726

RESUMO

A growing number of studies use data before and after treatment initiation in groups exposed to different treatment strategies to estimate "causal effects" using a ratio measure called the prior event rate ratio (PERR). Here, we offer a causal interpretation for PERR and its additive scale analog, the prior event rate difference (PERD). We show that causal interpretation of these measures requires untestable rate-change assumptions about the relationship between 1) the change of the counterfactual rate before and after treatment initiation in the treated group under hypothetical intervention to implement the control strategy; and 2) the change of the factual rate before and after treatment initiation in the control group. The rate-change assumption is on the multiplicative scale for PERR but on the additive scale for PERD; the 2 assumptions hold simultaneously under testable, but unlikely, conditions. Even if investigators can pick the most appropriate scale, the relevant rate-change assumption might not hold exactly, so we describe sensitivity analysis methods to examine how assumption violations of different magnitudes would affect study results. We illustrate the methods using data from a published study of proton pump inhibitors and pneumonia.


Assuntos
Causalidade , Modelos Estatísticos , Farmacoepidemiologia , Pneumonia/induzido quimicamente , Inibidores da Bomba de Prótons/administração & dosagem , Projetos de Pesquisa , Estudos de Casos e Controles , Humanos , Reino Unido
18.
Anat Sci Int ; 96(1): 142-156, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32931001

RESUMO

Omeprazole is a potent inhibitor of gastric acid secretion. It was reported that omeprazole induced dramatic gastric mucosa morphologic changes from the resting state to the stimulated state. However, the effect of omeprazole administration on the ultrastructure and absorptive function of small intestines was largely unknown. Here, male Sprague-Dawley rats were daily treated with a single dose of omeprazole for 12 or 24 weeks. Ultrastructure intestinal mucosal change in duodenum, jejunum, and ileum was observed. We also determined small intestine inflammation, using intraepithelial lymphocytes activation. Finally, magnesium levels were measured in plasma, urine, feces, muscle, and bone to determine systemic magnesium balance. Omeprazole-treated rats had significantly decreased the width of tight junction, villous length, and absorptive area of duodenum, jejunum, and ileum compared to control rats. The small intestine of the omeprazole-treated group showed significantly higher intraepithelial lymphocytes activation levels compared with the control group. Lower secretory granules of Paneth cells at the base of the crypts were showed in omeprazole-treated rats. They also had significantly lower plasma, urinary, bone, and muscle Mg2+ contents indicating hypomagnesemia with systemic magnesium deficiency. In conclusion, prolonged omeprazole treatment-induced small intestinal inflammation and villous atrophy, which led to decrease small intestinal magnesium absorption in the condition of proton pump inhibitor-induced hypomagnesemia.


Assuntos
Ácido Gástrico/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/ultraestrutura , Omeprazol/administração & dosagem , Omeprazol/efeitos adversos , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Animais , Atrofia , Hipercalciúria/induzido quimicamente , Inflamação , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Ativação Linfocitária , Magnésio/metabolismo , Masculino , Microscopia Eletrônica de Transmissão , Nefrocalcinose/induzido quimicamente , Celulas de Paneth/efeitos dos fármacos , Celulas de Paneth/patologia , Ratos Sprague-Dawley , Erros Inatos do Transporte Tubular Renal/induzido quimicamente , Fatores de Tempo
19.
Life Sci ; 265: 118818, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33275985

RESUMO

AIM: Proton pump inhibitors (PPIs) are widely used drugs recently linked to chronic kidney disease. However, the invloved mechanisms remained elusive. Since defective autophagy is identified as a new culprit in the pathogenesis of diabetic nephropathy (DN), we aimed to trace the link of autophagy blockade by PPIs to the progression of DN with and without the standard therapy of metformin and enalapril. MAIN METHODS: Male CD1 albino mice (20-25 g) were randomly assigned to normal control or diabetic mice. Diabetes was induced by intraperitoneal streptozotocin (35 mg/kg) injection combined with high fat diet. DN mice were randomized to receive vehicle, lansoprazole (5 mg/kg), metformin (200 mg/kg), lansoprazole + metformin, metformin + enalapril (0.5 mg/kg) or the three drugs together, orally daily for four weeks. At the study end, albuminuria, fasting plasma glucose, HbA1c, renal functions and malondialdehyde were assessed. Renal tissues were examined microscopically, and autophagic changes were evaluated by immunohistochemical detection of LC3-II and p62. KEY FINDINGS: Consistent with autophagic blockade, lansoprazole increased both LC3II and p62 in the glomerular and tubular cells. This was associated with impaired creatinine clearance and renal functions, enhanced albuminuria, oxidative stress and augmented DN histopathological changes. Opposite effects on autophagy markers were observed by single or combined treatment of metformin with enalapril; which also ameliorated glycemic control and signs of DN. This improvement was mitigated by combination with lansoprazole. SIGNIFICANCE: Autophagy blockade by lansoprazole augmented diabetic nephropathy and opposed the reno-protective effects of metformin and enalapril. The use of PPIs in diabetes should be considered with great caution.


Assuntos
Autofagia/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/fisiopatologia , Lansoprazol/toxicidade , Inibidores da Bomba de Prótons/toxicidade , Albuminúria/etiologia , Animais , Nefropatias Diabéticas/prevenção & controle , Dieta Hiperlipídica , Enalapril/farmacologia , Lansoprazol/administração & dosagem , Masculino , Metformina/farmacologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , Estreptozocina
20.
Vet Clin North Am Small Anim Pract ; 51(1): 33-41, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33131917

RESUMO

A range of gastroprotective drugs are available for the treatment of esophagitis and gastroduodenal mucosal injury including acid suppressants (ie, histamine-2 receptor antagonists, proton pump inhibitors), coating agents, prostaglandin analogs, and antacids. Of these, the proton pump inhibitors are the most effective drugs for the medical treatment of upper gastrointestinal injury. However, proton pump inhibitors are not effective for all causes of upper gastrointestinal injury. The choice of gastroprotective drug should be guided by the cause and location of gastrointestinal injury and the potential for adverse effects.


Assuntos
Doenças do Cão/tratamento farmacológico , Úlcera Gástrica/veterinária , Animais , Antiácidos/administração & dosagem , Antiácidos/uso terapêutico , Cães , Antagonistas dos Receptores H2 da Histamina/administração & dosagem , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , Úlcera Gástrica/tratamento farmacológico
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