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1.
Medicine (Baltimore) ; 99(16): e19723, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32311961

RESUMO

BACKGROUND: To compare the efficacy and safety of combination of curcuminoid complex and diclofenac vs diclofenac alone in the treatment of knee osteoarthritis (OA). METHODS: In this randomized trial, 140 patients of knee OA received either curcuminoid complex 500 mg (BCM-95) with diclofenac 50 mg 2 times daily or diclofenac 50 mg alone 2 times daily for 28 days. Patients were assessed at baseline, day 14 and day 28. Primary efficacy measures were Knee injury and OA outcome score (KOOS) subscale at day 14 and day 28. Anti-ulcer effect and patient-physician's global assessment of therapy at day 28 were included as secondary endpoints. Safety after treatment was evaluated by recording adverse events and laboratory investigations. RESULTS: Both treatment groups showed improvement in primary endpoints at each evaluation visit. Patients receiving curcuminoid complex plus diclofenac showed significantly superior improvement in KOOS subscales, viz. pain and quality of life at each study visit (P < .001) when compared to diclofenac. Less number of patients required rescue analgesics in curcuminoid complex plus diclofenac group (3%) compared to diclofenac group (17%). The number of patients who required histamine 2 (H2) blockers was significantly less in curcuminoid complex plus diclofenac group compared to diclofenac group (6% vs 28%, respectively; P < .001). Adverse effects were significantly less in curcuminoid complex plus diclofenac group (13% vs 38% in diclofenac group; P < .001). Patient's and physician's global assessment of therapy favored curcuminoid complex plus diclofenac than diclofenac. CONCLUSION: Combination of curcuminoid complex and diclofenac showed a greater improvement in pain and functional capacity with better tolerability and could be a better alternative treatment option in symptomatic management of knee OA. TRIAL REGISTRATION: ISRCTN, ISRCTN10074826.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Diarileptanoides/uso terapêutico , Diclofenaco/efeitos adversos , Osteoartrite do Joelho/tratamento farmacológico , Úlcera Péptica/prevenção & controle , Curcuma , Feminino , Antagonistas dos Receptores Histamínicos H2/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico
2.
Rev Med Suisse ; 16(680): 268-271, 2020 Feb 05.
Artigo em Francês | MEDLINE | ID: mdl-32022492

RESUMO

Peptic ulcer induced upper gastrointestinal hemorrhage is a frequent digestive emergency and is one of the most common cause of hospitalization. There are several intrinsic risk factors for peptic ulcer bleed such as advanced age, previous gastro-intestinal hemorrhage, male sex and the presence of Helicobacter pylori. In high risk patients for peptic ulcer disease, gastric protection measures should be considered, most often by treatment with proton pump inhibitors. The eradication of Helicobacter pylori should also be discussed for long-term treatments.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/prevenção & controle , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/patogenicidade , Humanos , Úlcera Péptica/complicações , Inibidores da Bomba de Prótons/uso terapêutico
4.
Daru ; 27(1): 317-327, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31218527

RESUMO

BACKGROUND: Trachyspermum ammi (L.) Sprague is used for treating gastrointestinal disorders. Several studies indicated gastric antiulcer activity of T. ammi extract, yet the effect of its essential oil has not been studied on. OBJECTIVES: The present study evaluates chemical composition of T. ammi essential oil and anti-peptic ulcer effect of the essential oil as well as its three major components in ethanol induced-gastric ulcers in rats. METHODS: Primarily chemical composition of the essential oil was analyzed by gas chromatography-mass spectrometry (GC/MS). Rats received the essential oil (500, 250, 125, 62.5, 31.25 mg/kg), thymol (30, 100 mg/kg), para-cymene (100, 150 mg/kg) and gamma-terpinene (100, 150 mg/kg) using gavage tube along with ethanol 80%. Finally, dissected stomachs were assessed both macroscopically and microscopically to evaluate anti-ulcerative effect of the essential oil and the pure compounds. Moreover, molecular docking was utilized to explore the interactive behavior of the main components with active site residues of H+/K+ ATPase. RESULTS: Analysis of the essential oil indicated that para-cymene (37.18%), gamma-terpinene (35.36%) and thymol (20.51%) are the main components. Administration of different doses of the essential oil noticeably diminished the number of peptic ulcers in a dose-dependent manner. Among the main components, thymol was more potent than para-cymene and gamma-terpinene. Administration of the essential oil (500 mg/kg) and thymol (100 mg/kg) observed maximum inhibition percentage (98.58% and 79.37%, respectively). Molecular docking study provides the evidence of thymol ability to inhibit H+/K+ ATPase. CONCLUSIONS: The findings revealed that T. ammi essential oil can be applied to treat gastric ulcer as a natural agent. Graphical abstract.


Assuntos
Ammi/química , Etanol/efeitos adversos , Óleos Voláteis/administração & dosagem , Úlcera Péptica/tratamento farmacológico , Animais , Monoterpenos Cicloexânicos/administração & dosagem , Monoterpenos Cicloexânicos/isolamento & purificação , Monoterpenos Cicloexânicos/farmacologia , Cimenos/administração & dosagem , Cimenos/isolamento & purificação , Cimenos/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação para Baixo , Cromatografia Gasosa-Espectrometria de Massas , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Simulação de Acoplamento Molecular , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/metabolismo , Óleos Vegetais/administração & dosagem , Óleos Vegetais/química , Óleos Vegetais/farmacologia , Ratos , Timol/administração & dosagem , Timol/isolamento & purificação , Timol/farmacologia
5.
Gastroenterology ; 157(2): 403-412.e5, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31054846

RESUMO

BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528). CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.


Assuntos
Anticoagulantes/efeitos adversos , Doenças Cardiovasculares/prevenção & controle , Hemorragia Gastrointestinal/prevenção & controle , Pantoprazol/administração & dosagem , Úlcera Péptica/prevenção & controle , Inibidores da Bomba de Prótons/administração & dosagem , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/epidemiologia , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Resultado do Tratamento
6.
J Gastroenterol Hepatol ; 34(9): 1517-1522, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30919492

RESUMO

BACKGROUND AND AIM: Long-term use of dual antiplatelets is increasing, and most patients need primary peptic ulcer prophylaxis. The long-term use of proton pump inhibitors (PPIs) is associated with adverse events. We evaluated the efficacy of rebamipide for peptic ulcer prevention. METHODS: This randomized controlled trial was conducted between July 2014 and November 2017. Patients receiving dual antiplatelets for ≥ 1 year with no history of peptic ulcer bleeding or perforation were recruited and randomly assigned to the rebamipide (300 mg/day) group or the placebo group. Patients who used proton pump inhibitors were excluded. The primary endpoint was a new mucosal break on esophagogastroduodenoscopy at 3 or 12 months after treatment initiation. The secondary endpoints were hematocrit changes from the baseline, gastrointestinal bleeding, and chest pain. Antiplatelet function was assessed. RESULTS: In total, 95 eligible patients were identified; 12 were excluded, and 83 patients were randomized, with 66 (79.5%) and 59 (71.1%) patients eligible at the 3- and 12-month follow ups, respectively. The baseline characteristics were equivalent between the groups. During the 12 months of follow up, 13 patients (43.3%) taking rebamipide and 19 (65.5%) taking the placebo experienced mucosal injury (P = 0.07). Two patients (6.7%) taking rebamipide and eight (27.6%) taking the placebo had peptic ulcers ≥ 5 mm or < 5 mm with pigmented spots (P = 0.03). The changes in hematocrit were not different between the two groups. Neither bleeding ulcers nor chest pain was observed. CONCLUSION: Rebamipide is safe and may prevent peptic ulcers ≥ 5 mm in diameter or those with pigmented spots in patients receiving dual antiplatelets for 1 year (NCT02166008).


Assuntos
Alanina/análogos & derivados , Antiulcerosos/administração & dosagem , Aspirina/efeitos adversos , Cilostazol/efeitos adversos , Clopidogrel/efeitos adversos , Úlcera Péptica/prevenção & controle , Inibidores da Agregação de Plaquetas/efeitos adversos , Quinolonas/administração & dosagem , Ticagrelor/efeitos adversos , Idoso , Alanina/administração & dosagem , Alanina/efeitos adversos , Antiulcerosos/efeitos adversos , Aspirina/administração & dosagem , Cilostazol/administração & dosagem , Clopidogrel/administração & dosagem , Citoproteção , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/patologia , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Quinolonas/efeitos adversos , Tailândia , Ticagrelor/administração & dosagem , Fatores de Tempo , Resultado do Tratamento
7.
Gastrointest Endosc ; 89(2): 357-363.e2, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30670179

RESUMO

BACKGROUND AND AIMS: Although erosions and ulcerations are the most common small-bowel abnormalities found on wireless capsule endoscopy (WCE), a computer-aided detection method has not been established. We aimed to develop an artificial intelligence system with deep learning to automatically detect erosions and ulcerations in WCE images. METHODS: We trained a deep convolutional neural network (CNN) system based on a Single Shot Multibox Detector, using 5360 WCE images of erosions and ulcerations. We assessed its performance by calculating the area under the receiver operating characteristic curve and its sensitivity, specificity, and accuracy using an independent test set of 10,440 small-bowel images including 440 images of erosions and ulcerations. RESULTS: The trained CNN required 233 seconds to evaluate 10,440 test images. The area under the curve for the detection of erosions and ulcerations was 0.958 (95% confidence interval [CI], 0.947-0.968). The sensitivity, specificity, and accuracy of the CNN were 88.2% (95% CI, 84.8%-91.0%), 90.9% (95% CI, 90.3%-91.4%), and 90.8% (95% CI, 90.2%-91.3%), respectively, at a cut-off value of 0.481 for the probability score. CONCLUSIONS: We developed and validated a new system based on CNN to automatically detect erosions and ulcerations in WCE images. This may be a crucial step in the development of daily-use diagnostic software for WCE images to help reduce oversights and the burden on physicians.


Assuntos
Endoscopia por Cápsula , Doenças do Íleo/diagnóstico , Doenças Inflamatórias Intestinais/diagnóstico , Intestino Delgado/patologia , Doenças do Jejuno/diagnóstico , Redes Neurais de Computação , Reconhecimento Automatizado de Padrão , Úlcera/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/efeitos adversos , Área Sob a Curva , Aprendizado Profundo , Úlcera Duodenal/diagnóstico , Úlcera Duodenal/etiologia , Úlcera Duodenal/patologia , Feminino , Humanos , Doenças do Íleo/etiologia , Doenças do Íleo/patologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/patologia , Doenças do Jejuno/etiologia , Doenças do Jejuno/patologia , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/diagnóstico , Úlcera Péptica/patologia , Curva ROC , Sensibilidade e Especificidade , Software , Úlcera/etiologia , Úlcera/patologia
8.
J Gastroenterol Hepatol ; 34(3): 517-525, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30408229

RESUMO

BACKGROUND AND AIM: Owing to wide-spread use, low-dose aspirin (LDA) produces a substantial amount of peptic ulcer disease. Current guidelines are ambivalent about the need for Helicobacter pylori eradication to protect against LDA ulcers. This study aimed to determine, through meta-analysis, if (and by how much) infection alters the baseline risk of peptic ulcers during LDA therapy. METHODS: Literature screening was performed in MEDLINE and EMBASE from inception to May 2018. Original studies reporting prevalence or incidence of uncomplicated ulcers in LDA users were included. Ulcer endpoints needed to be specified separately, according to H. pylori infection status. Meta-analysis was performed in MIX 2.0 Pro. RESULTS: Ten cross-sectional studies and seven randomized controlled trials were included (n = 5964). The pooled odds ratios with 95% confidence intervals (CI) for the risk of LDA ulcers in H. pylori-positive versus H. pylori-negative individuals were 1.68 (95%CI 1.40-2.02) and 1.65 (95%CI 1.29-2.08) under fixed-effects and random-effects models, respectively. Heterogeneity among studies was minimal (I2  = 26.9%). After adjusting for the protective effects of antisecretory drugs, the odds ratios increased to 1.94 (95%CI 1.54-2.46). CONCLUSION: This analysis suggests that H. pylori increases the risk of LDA ulcers by almost 70% in a population where some were taking proton pump inhibitors and/or other acid suppressants. Without antisecretory drugs, the risk almost doubles. Clinically, these findings may support the use of a test-and-treat approach to H. pylori in LDA users, particularly those already at higher risk of developing peptic ulcers.


Assuntos
Aspirina/efeitos adversos , Gastrite/complicações , Gastrite/microbiologia , Infecções por Helicobacter , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/etiologia , Aspirina/administração & dosagem , Bases de Dados Bibliográficas , Helicobacter pylori , Humanos , Incidência , Úlcera Péptica/epidemiologia , Úlcera Péptica/prevenção & controle , Prevalência , Risco
9.
Digestion ; 99(1): 66-71, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30554208

RESUMO

BACKGROUND AND AIM: Helicobacter pylori infection is a primary cause of gastroduodenal ulcers. To investigate whether there is an association between H. pylori infection and small intestinal mucosal injury. METHODS: Patients were selected from a general pool of subjects who underwent capsule endoscopy for current or past obscure gastrointestinal bleeding. Characteristics including age, gender, history, treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and/or acid suppressant, diagnosis, and H. pylori infection were investigated. Patients infected with H. pylori had positive test result, ranging 30 days before to 30 days after capsule endoscopy. Patients diagnosed with inflammatory diseases, malignant tumors, etc. were excluded. All video images were re-evaluated to count small intestinal mucosal breaks. Eligible patient variables were compared. RESULTS: A total of 92 patients (30 infected with H. pylori/62 uninfected) were eligible. By univariate analysis of the number of mucosal breaks, patients treated with NSAIDs were found to have more mucosal breaks than patients untreated (38%: 8/21 vs. 18%: 13/71; p = 0.004), and the possible association was detected between patients infected with H. pylori and those who were not (67%: 14/21 vs. 37%: 26/71; p = 0.081). When comparing the H. pylori infected and uninfected patients, the rate of patients with mucosal breaks was greater in infected patients (47%: 14/30 vs. 11%: 7/62; p = 0.001). After excluding patients treated with NSAIDs, the number of mucosal breaks was also greater in patients infected with H. pylori (1.2 ± 1.5 vs. 0.38 ± 0.62; p = 0.001). CONCLUSION: There is a possibility that H. pylori infection induces small intestinal mucosal injury.


Assuntos
Infecções por Helicobacter/complicações , Helicobacter pylori , Enteropatias/microbiologia , Úlcera Péptica/microbiologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Endoscopia por Cápsula , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Humanos , Enteropatias/induzido quimicamente , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/microbiologia , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Projetos Piloto , Estudos Retrospectivos
10.
Life Sci ; 217: 164-168, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30528722

RESUMO

AIMS: Memantine is a commonly used drug in treating Alzheimer disease. In the current work, we aimed to evaluate the gastro-protective effect of memantine in indomethacin-induced peptic ulcer in rats. MAIN METHODS: Peptic ulcer induced by indomethacin and memantine administered either alone or in combination with glibenclamide or nitric oxide synthase (NOS) inhibitor. Ulcer index done and malondialdehyde (MDA), superoxide dismutase (SOD), total nitrites, expression of tumor necrosis factor-α (TNF-α) and expression of nuclear factor kappa B (NF-κB) were measured in gastric mucosa. KEY FINDINGS: Memantine reduced ulcer index, reduced MDA, increased SOD, increased total nitrites and reduced expression of both TNF-α and NF-κB. Glibenclamide and not NOS inhibitor abolished the gastroprotective effect of memantine. SIGNIFICANCE: Memantine was protective against indomethacin-induced peptic ulcer in rats mostly by affecting potassium channels, antioxidative stress and anti-inflammatory actions.


Assuntos
Antiulcerosos/uso terapêutico , Indometacina , Memantina/uso terapêutico , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/tratamento farmacológico , Canais de Potássio/metabolismo , Animais , Glibureto/uso terapêutico , Masculino , Óxido Nítrico Sintase/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Úlcera Péptica/metabolismo , Úlcera Péptica/patologia , Ratos , Ratos Wistar
11.
Stat Methods Med Res ; 28(2): 532-554, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-28936917

RESUMO

Robust inference of a low-dimensional parameter in a large semi-parametric model relies on external estimators of infinite-dimensional features of the distribution of the data. Typically, only one of the latter is optimized for the sake of constructing a well-behaved estimator of the low-dimensional parameter of interest. Optimizing more than one of them for the sake of achieving a better bias-variance trade-off in the estimation of the parameter of interest is the core idea driving the general template of the collaborative targeted minimum loss-based estimation procedure. The original instantiation of the collaborative targeted minimum loss-based estimation template can be presented as a greedy forward stepwise collaborative targeted minimum loss-based estimation algorithm. It does not scale well when the number p of covariates increases drastically. This motivates the introduction of a novel instantiation of the collaborative targeted minimum loss-based estimation template where the covariates are pre-ordered. Its time complexity is O(p) as opposed to the original O(p2) , a remarkable gain. We propose two pre-ordering strategies and suggest a rule of thumb to develop other meaningful strategies. Because it is usually unclear a priori which pre-ordering strategy to choose, we also introduce another instantiation called SL-C-TMLE algorithm that enables the data-driven choice of the better pre-ordering strategy given the problem at hand. Its time complexity is O(p) as well. The computational burden and relative performance of these algorithms were compared in simulation studies involving fully synthetic data or partially synthetic data based on a real world large electronic health database; and in analyses of three real, large electronic health databases. In all analyses involving electronic health databases, the greedy collaborative targeted minimum loss-based estimation algorithm is unacceptably slow. Simulation studies seem to indicate that our scalable collaborative targeted minimum loss-based estimation and SL-C-TMLE algorithms work well. All C-TMLEs are publicly available in a Julia software package.


Assuntos
Modelos Estatísticos , Idoso , Algoritmos , Anti-Inflamatórios não Esteroides/efeitos adversos , Simulação por Computador , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Estudos Observacionais como Assunto , Úlcera Péptica/induzido quimicamente , Úlcera Péptica Perfurada/induzido quimicamente , Pontuação de Propensão
13.
Am J Hosp Palliat Care ; 36(2): 158-168, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30165748

RESUMO

BACKGROUND:: Corticosteroids are frequently utilized in the palliative care setting to combat symptoms such as fatigue, dyspnea, pain, weakness, anorexia, cachexia, nausea, and vomiting. Often times, adverse effects arise with corticosteroid use, and it is unclear whether switching to another corticosteroid would reduce the risk of specific adverse effects or what measures can be taken to alleviate the adverse effects. OBJECTIVE:: This article aims to review the differentiating pharmacokinetics, potency, and adverse effect profiles of corticosteroids and summarize their clinical applicability. METHODS:: A literature review of "corticosteroids" and "palliative care" was performed using the PubMed database through July 2018. Original studies relevant to the purpose of this study were identified and those that met inclusion criteria were included. RESULTS:: Although corticosteroids share many common factors, including similar pharmacokinetic, pharmacodymanic, and adverse effect profiles, they have significant differences when the details of these variables are reviewed. Providers that prescribe corticosteroids for symptom management should be aware of these differences and the recommended management strategies. CONCLUSIONS:: Recognition of corticosteroid induced adverse effect profiles and possible management strategies is crucial to optimal symptom management in palliative care patients.


Assuntos
Corticosteroides/efeitos adversos , Corticosteroides/farmacocinética , Doenças Cardiovasculares/induzido quimicamente , Delírio/induzido quimicamente , Doenças do Sistema Endócrino/induzido quimicamente , Feminino , Meia-Vida , Humanos , Masculino , Osteoporose/induzido quimicamente , Cuidados Paliativos , Úlcera Péptica/induzido quimicamente
14.
Scand J Gastroenterol ; 53(12): 1490-1495, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30509124

RESUMO

OBJECTIVES: Direct oral anticoagulants (DOACs) are effective in the prevention and treatment of thromboembolism; however, they are associated with upper gastrointestinal bleeding (UGIB). In this study, we evaluated the efficacy of gastroprotective agents (GPAs) in reducing the risk of UGIB in patients receiving DOACs. METHODS: We retrospectively reviewed the medical records of 2076 patients who received DOACs for the prevention or treatment of thromboembolic events between January 2008 and July 2016. A cumulative incidence analysis using the Kaplan-Meier method was performed to determine the rate of UGIB and its association with GPAs administration. RESULTS: Of the 2076 patients, 360 received GPAs. Over the follow-up period (1160 person-years), one patient in the GPA group (0.7 per 100 person-years) and 29 patients in the non-GPA group (2.8 per 100 person-years) developed UGIB (p = .189). In the multivariate analysis, UGIB was associated with older age (hazard ratio (HR), 1.041; p = .048), a history of peptic ulcer or UGIB (HR, 5.931; p < .001), and concomitant use of antiplatelet agents (HR, 3.121; p = .014). GPAs administration did not reduce the risk of UGIB (p = .289). However, based on the subgroup analysis of 225 patients with concomitant use of antiplatelet agents or a history of peptic ulcer or UGIB, the GPA group (0 per 100 person-years) showed reduced incidence of UGIB compared with the non-GPA group (11.3 per 100 person-years) (p = .065). CONCLUSIONS: The prophylactic use of GPAs could reduce the risk of UGIB in patients receiving DOACs who have risk factors, such as concomitant use of antiplatelet agents or a history of peptic ulcer or UGIB.


Assuntos
Anticoagulantes/efeitos adversos , Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/prevenção & controle , Antagonistas dos Receptores Histamínicos H2/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/complicações , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Tromboembolia/tratamento farmacológico , Tromboembolia/prevenção & controle , Adulto Jovem
16.
J Gastroenterol ; 53(12): 1253-1260, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29948304

RESUMO

BACKGROUND: We aimed to identify the adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotics on the upper gastrointestinal (GI) mucosa in a clinical setting as a case-control study using a large-scale medical database in Japan. METHODS: We evaluated the risk of upper GI mucosal injuries in patients receiving NSAIDs and antithrombotics using the Japan Medical Data Center claims database with data for 13 million accumulated patients, from January 2009 to December 2014. Endoscopically evaluated upper GI mucosal injuries were peptic ulcers (n = 143,271), upper GI bleeding (n = 10,545), and gastroesophageal reflux disease (n = 154,755). For each patient, ten controls were matched by age, sex, and diagnosis month. RESULTS: The odds ratio (OR) for peptic ulcers was 1.45, 1.31, 1.50, 1.53, and 1.62; for upper GI bleeding: 1.76, 1.62, 1.96, 1.82, and 2.38; and for gastroesophageal reflux disease: 1.54, 1.41, 1.89, 1.67, and 1.91 for NSAIDs, COX-2 selective inhibitors, low-dose aspirin, antiplatelet drugs, and anticoagulants, respectively (all statistically significant: P < 0.001). Polypharmacy with NSAIDs and antithrombotic drugs increased the risk of upper GI injuries compared with single-drug therapy. The injury risk was also increased by lifestyle-related diseases, including diabetes mellitus and hyperlipidemia. CONCLUSIONS: This case-control study using the large organized Japanese claims database provided the risk of upper GI mucosal injuries in patients receiving NSAIDs and antithrombotic drugs.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Fibrinolíticos/efeitos adversos , Refluxo Gastroesofágico/epidemiologia , Hemorragia Gastrointestinal/epidemiologia , Úlcera Péptica/epidemiologia , Adulto , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Estudos de Casos e Controles , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Bases de Dados Factuais , Feminino , Fibrinolíticos/administração & dosagem , Refluxo Gastroesofágico/induzido quimicamente , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Polimedicação , Fatores de Risco , Adulto Jovem
17.
J Physiol Pharmacol ; 69(6)2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30802217

RESUMO

Capsaicin-sensitive sensory nerves are densely distributed in the gastrointestinal system and involved in maintenance of gastrointestinal mucosal integrity. capsaicin selectively stimulates nociceptive neurons and its action is mediated through the transient receptor potential channel vanilloid type 1 (TRPV1) receptor. Activation TRPV1 receptors that play a fundamental role in pain signaling, may also exert protective effects against gastrointestinal injury. The present study was performed to investigate and compare the vulnerability of gastric as well as small intestinal mucosa to ulcerogenic action of indomethacin (IM) in mice with genetically deleted TRPV1 receptor (TRPV1 KO) and in C57/BL6/J mice. IM-induced injury was assessed macroscopically as well as histologically; the somatic pain sensitivity was estimated by tail flick latency (tail flick test); plasma corticosterone levels and body weight were also monitored. A single IM administration (35 mg/kg, subcutaneously) into pre-starving (24 h) mice caused the formation of gastric erosions 4 h later and, then, after refeeding, induced formation of the small intestinal injury which was visible 24, 48, 72 h after IM administration. Although IM-induced gastrointestinal injury was detectable in both C57/BL6/J and TRPV1 KO mice, area of gastric damage was greater in C57/BL6/J than in TRPV1 KO mice, whereas the small intestinal injury (48 and 72 h after IM injection), on the contrary, prevailed in TRPV1 KO mice compared to C57/BL6/J mice. In 24 h after IM injection, the total area of intestinal injury did not differ in C57BL6/J and TRPV1 KO mice, however histological score was higher in TRPV1 KO mice than C57BL6/J mice. TRPV1 KO mice showed the increased tail flick latencies and the lacking IM-induced corticosterone rise. The data suggest that in TRPV1 KO mice the gastric mucosa is less vulnerable to ulcerogenic action of IM compared to C57/BL6/J mice, however, their small intestinal mucosa, on the contrary, is more vulnerable to the ulcerogenic action than in C57/BL6/J mice.


Assuntos
Mucosa Gástrica/efeitos dos fármacos , Indometacina/toxicidade , Mucosa Intestinal/efeitos dos fármacos , Canais de Cátion TRPV/genética , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Capsaicina/farmacologia , Mucosa Gástrica/patologia , Mucosa Intestinal/patologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Fatores de Tempo
18.
Ter Arkh ; 90(8): 95-100, 2018 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-30701943

RESUMO

The review analyzes the main etiological and pathogenetic mechanisms of the development of NSAID-enteropathy. Particular attention is paid to the role of intestinal microbiota in the manifestation and progression of NSAID-enteropathy. The special role of probiotics in the prevention and treatment of NSAIDs enteropathy is considered.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Gastroenterite/induzido quimicamente , Úlcera Péptica/induzido quimicamente , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Gastroenterite/microbiologia , Gastroenterite/prevenção & controle , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Microbiota/efeitos dos fármacos , Úlcera Péptica/microbiologia , Úlcera Péptica/prevenção & controle , Probióticos/uso terapêutico
19.
Int J Pharm Pract ; 26(4): 369-372, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29159948

RESUMO

OBJECTIVES: To identify prescribing patterns of antiulcer agents in patients on low-dose aspirin (LDA) and to evaluate the number of gastrointestinal (GI) risk factors of the patients. METHODS: A retrospective chart review of patients taking LDA was conducted at the National Cerebral and Cardiovascular Center in Japan. The rate of concomitant use of antiulcer agents and the risk of each patient to develop GI complications were evaluated. RESULTS: Of the 314 patients, 64 were not on antiulcer agents and 55 of them had >1 risk factor. More patients not on antiulcer agents had started LDA before hospitalization. CONCLUSION: The rate of coprescribing antiulcer agents with LDA was high. However, the timing of initiating LDA therapy affected the prescribing pattern of antiulcer agents.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Antiulcerosos/uso terapêutico , Aspirina/efeitos adversos , Prescrições de Medicamentos/estatística & dados numéricos , Úlcera Péptica/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Padrões de Prática Médica/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
20.
J Asthma ; 55(6): 651-658, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28925768

RESUMO

OBJECTIVE: Systemic glucocorticoids (SGCs) are a treatment option for severe asthma but are associated with the development of adverse events (AEs). Evidence on the extent of SGC use and the relationship between SGC dose and AE risk in severe asthma is limited. METHODS: Patients with severe asthma (Global Initiative for Asthma step 4/5), with no SGC use during the <6-12 months before severe asthma determination (index date) were identified in the UK-based Clinical Practice Research Datalink database (2004-2012). Patients were assessed for SGC exposure and an incident diagnosis of an SGC-related AE (cataracts, diabetes, myocardial infarction [MI], osteoporosis, peptic ulcer or stroke) during the 8-year observation phase. The dose-related risk of an SGC-related AE was determined using AE-specific Cox proportional hazards models. RESULTS: Overall, 75% of 60,418 patients identified with severe asthma received SGC during the 8-year follow-up, with the majority receiving an average of >0-≤2.5 mg/day. The risk of diabetes (hazard ratio [HR]:1.20 [95% confidence interval (CI): 1.11, 1.30]), MI (HR: 1.25 [95% CI: 1.09, 1.43]) and osteoporosis (HR: 1.64 [95% CI: 1.51, 1.78]) was increased at low SGC doses (0-2.5 mg/day), with further risk increases at doses >2.5 mg/day versus no SGC use. Compared with no SGC use, SGC increased the risk of peptic ulcer in a non-dose-dependent manner, but the risk of stroke was unchanged. CONCLUSIONS: Most patients with severe asthma are exposed to SGC, which increases SGC-related AE risk. This suggests that SGC exposure should be minimized as recommended by asthma treatment guidelines.


Assuntos
Asma/tratamento farmacológico , Glucocorticoides/efeitos adversos , Administração Oral , Adulto , Idoso , Asma/diagnóstico , Catarata/induzido quimicamente , Catarata/epidemiologia , Bases de Dados Factuais/estatística & dados numéricos , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/administração & dosagem , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/epidemiologia , Osteoporose/induzido quimicamente , Osteoporose/epidemiologia , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Reino Unido/epidemiologia , Adulto Jovem
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