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1.
Medicina (B Aires) ; 79(4): 315-321, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31487255

RESUMO

One of the main pillars of acute ischemic stroke management is antiplatelet therapy. Different treatment schemes have been compared, suggesting that the combination of multiple antiplatelet drugs is associated with a reduced risk of stroke recurrence. However, it has also been associated with an increased risk of bleeding complications which, in the long term, surpass the mentioned benefits. However, considering that most stroke recurrences occur i n the short term, a time limited double antiplatelet scheme could result in significant benefits to patients with acute ischemic stroke. On this basis, we conducted a rapid systematic review of the literature in order to evaluate the effects of a short-term double antiplatelet therapy both on stroke recurrence and complications. All trials comparing double versus single antiplatelet therapy in patients with acute ischemic stroke were included. Results showed that double therapy reduces recurrence risk but probably marginally increases major bleeding complications. We suggest double antiplatelet therapy for the initial management of patients with minor (Score NIH < or equal to 3 or transient isquemic attack -TIA) acute ischemic stroke.


Assuntos
Aspirina/administração & dosagem , Benzodiazepinas/administração & dosagem , Clopidogrel/administração & dosagem , Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/prevenção & controle , Inibidores da Agregação de Plaquetas/administração & dosagem , Poliaminas/administração & dosagem , Quimioterapia Combinada , Humanos , Recidiva , Prevenção Secundária
2.
Lancet ; 394(10199): 672-683, 2019 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-31448738

RESUMO

BACKGROUND: A fixed-dose combination therapy (polypill strategy) has been proposed as an approach to reduce the burden of cardiovascular disease, especially in low-income and middle-income countries (LMICs). The PolyIran study aimed to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan for primary and secondary prevention of cardiovascular disease. METHODS: The PolyIran study was a two-group, pragmatic, cluster-randomised trial nested within the Golestan Cohort Study (GCS), a cohort study with 50 045 participants aged 40-75 years from the Golestan province in Iran. Clusters (villages) were randomly allocated (1:1) to either a package of non-pharmacological preventive interventions alone (minimal care group) or together with a once-daily polypill tablet (polypill group). Randomisation was stratified by three districts (Gonbad, Aq-Qala, and Kalaleh), with the village as the unit of randomisation. We used a balanced randomisation algorithm, considering block sizes of 20 and balancing for cluster size or natural log of the cluster size (depending on the skewness within strata). Randomisation was done at a fixed point in time (Jan 18, 2011) by statisticians at the University of Birmingham (Birmingham, UK), independent of the local study team. The non-pharmacological preventive interventions (including educational training about healthy lifestyle-eg, healthy diet with low salt, sugar, and fat content, exercise, weight control, and abstinence from smoking and opium) were delivered by the PolyIran field visit team at months 3 and 6, and then every 6 months thereafter. Two formulations of polypill tablet were used in this study. Participants were first prescribed polypill one (hydrochlorothiazide 12·5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg). Participants who developed cough during follow-up were switched by a trained study physician to polypill two, which included valsartan 40 mg instead of enalapril 5 mg. Participants were followed up for 60 months. The primary outcome-occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke)-was centrally assessed by the GCS follow-up team, who were masked to allocation status. We did intention-to-treat analyses by including all participants who met eligibility criteria in the two study groups. The trial was registered with ClinicalTrials.gov, number NCT01271985. FINDINGS: Between Feb 22, 2011, and April 15, 2013, we enrolled 6838 individuals into the study-3417 (in 116 clusters) in the minimal care group and 3421 (in 120 clusters) in the polypill group. 1761 (51·5%) of 3421 participants in the polypill group were women, as were 1679 (49·1%) of 3417 participants in the minimal care group. Median adherence to polypill tablets was 80·5% (IQR 48·5-92·2). During follow-up, 301 (8·8%) of 3417 participants in the minimal care group had major cardiovascular events compared with 202 (5·9%) of 3421 participants in the polypill group (adjusted hazard ratio [HR] 0·66, 95% CI 0·55-0·80). We found no statistically significant interaction with the presence (HR 0·61, 95% CI 0·49-0·75) or absence of pre-existing cardiovascular disease (0·80; 0·51-1·12; pinteraction=0·19). When restricted to participants in the polypill group with high adherence, the reduction in the risk of major cardiovascular events was even greater compared with the minimal care group (adjusted HR 0·43, 95% CI 0·33-0·55). The frequency of adverse events was similar between the two study groups. 21 intracranial haemorrhages were reported during the 5 years of follow-up-ten participants in the polypill group and 11 participants in the minimal care group. There were 13 physician-confirmed diagnoses of upper gastrointestinal bleeding in the polypill group and nine in the minimal care group. INTERPRETATION: Use of polypill was effective in preventing major cardiovascular events. Medication adherence was high and adverse event numbers were low. The polypill strategy could be considered as an additional effective component in controlling cardiovascular diseases, especially in LMICs. FUNDING: Tehran University of Medical Sciences, Barakat Foundation, and Alborz Darou.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Combinação de Medicamentos , Prevenção Secundária/métodos , Adulto , Idoso , Anticolesterolemiantes/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Aspirina/administração & dosagem , Atorvastatina/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/efeitos dos fármacos , Diabetes Mellitus/epidemiologia , Enalapril/administração & dosagem , Feminino , Humanos , Hidroclorotiazida/administração & dosagem , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Valsartana/administração & dosagem
4.
Ann Hematol ; 98(10): 2267-2271, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31388698

RESUMO

Silent brain lesions might be associated with overt cerebrovascular accident over time in beta thalassemia major (BTM) and intermediate (BTI). Aspirin may be protective in these patients. We evaluated brain magnetic resonance imaging (MRI) in thalassemia patients to see whether aspirin is protective or not. A historical cohort study was conducted on 35 thalassemia patients, 22 BTI, and 13 BTM patients at Shiraz Hematology Research Center in 2018. Median age of the patients was 32 years and ranged from 8 to 42 years. Twenty-four patients (68.6%) were females. Overall frequency of white matter lesions (WMLs) in the first MRI was 10 patients (28.6%). After 3 years, 3 patients developed new lesions and the frequency of WMLs was 13 patients (37.1%) in the second MRI. Moreover, in 3 patients, number of WMLs increased. Patients with new lesions or more lesions compared to the baseline were significantly older than the other group (median age 36.5 years vs. 31 years, P = 0.046). Regarding aspirin consumption, only 1 patient (16.7%) of patients with new lesions was using aspirin compared to 10 (34.5%) of the other group (P = 0.640). The high-risk patients with thrombocytosis, splenectomy, severe iron overload, and older age (> 30 years) should be under close follow-up and evaluated on a regular periodic basis as well as brain MRI at least once every 3 years. Aspirin could be protective against new or progressive brain lesions so that low-dose aspirin is recommended in high-risk thalassemia patients.


Assuntos
Aspirina/administração & dosagem , Imagem por Ressonância Magnética , Acidente Vascular Cerebral , Talassemia beta , Adolescente , Adulto , Criança , Feminino , Seguimentos , Humanos , Masculino , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Talassemia beta/complicações , Talassemia beta/diagnóstico por imagem , Talassemia beta/tratamento farmacológico , Talassemia beta/epidemiologia
5.
Can Assoc Radiol J ; 70(3): 300-306, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31376886

RESUMO

PURPOSE: Arteriovenous fistulas and grafts, necessary for hemodialysis, may develop stenoses due to neointimal hyperplasia, which often require percutaneous transluminal angioplasty. Patient and lesion characteristics were evaluated prior to angioplasty and were correlated with 1- and 6-month outcomes. MATERIALS AND METHODS: This was an observational study of African American hemodialysis patients who presented for angioplasty of a dysfunctional fistula or graft. Clinical outcomes were ascertained from dialysis facilities 1 month and 6 months after angioplasty. One-month clinical success was defined as dialyzer blood flows of 450 mL/min without complications or interval shunt thrombosis, interventions, or loss of access, which was rarely achieved at 6 months. Logistic regression models were used to evaluate associations of clinical variables with outcomes. RESULTS: There were 150 stenoses treated during 99 procedures performed on 82 patients. The clinical success rate at one month was 67% with no complications as a result of the percutaneous transluminal angioplasty. Success at 1 month was positively associated with use of aspirin (P = .005) and with referral for high venous pressures (P = .004). Six-month data were available for 81 procedures, with 45.7% requiring repeat angioplasty and 12.3% suffering major complications (thrombectomy, revision surgery, or access abandonment). Major complications were seen predominantly in patients who were not receiving aspirin. CONCLUSIONS: Aspirin use and high venous pressure were associated with 1-month clinical success and fewer major complications at 6 months. Future work should investigate biologic mechanisms of action of aspirin and long-term effects of use to maintain vascular access.


Assuntos
Afro-Americanos/estatística & dados numéricos , Angioplastia/métodos , Fístula Arteriovenosa/terapia , Diálise Renal/efeitos adversos , Anti-Inflamatórios não Esteroides/administração & dosagem , Fístula Arteriovenosa/etiologia , Aspirina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
6.
Gastroenterology ; 157(2): 403-412, Aug., 2019. tabela, grafico
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1022748

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. (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/prevenção & controle , Aspirina/administração & dosagem , Método Duplo-Cego , Relação Dose-Resposta a Droga , Hemorragia Gastrointestinal/prevenção & controle , Anticoagulantes/administração & dosagem
8.
Expert Rev Clin Pharmacol ; 12(8): 771-780, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31269825

RESUMO

Introduction: The current approach of using only antiplatelet therapy for secondary prevention leaves a substantial risk of recurrent cardiovascular complications and mortality. Areas covered: In this manuscript, the role of coagulation in atherothrombosis is reviewed, as well as the impact of vascular doses of rivaroxaban on major cardiovascular outcomes and major adverse limb events. Expert opinion: In COMPASS, among patients with coronary heart disease and/or peripheral artery disease, compared to aspirin, the addition of rivaroxaban 2.5 mg twice daily to aspirin, significantly reduced the risk of major atherosclerotic outcomes, cardiovascular death and death for any cause, with a significant increase in the risk of major bleeding, but not fatal or intracranial bleedings. Preclinical data strongly suggest that rivaroxaban exerts vascular protection through different mechanisms, including improvement of endothelial functionality and fibrinolytic activity at endothelium, anti-inflammatory properties, and platelet-dependent thrombin generation. All these data indicate that among patients with atherosclerotic vascular disease, the addition of rivaroxaban 2.5 mg may provide further vascular protection.


Assuntos
Aterosclerose/prevenção & controle , Inibidores do Fator Xa/administração & dosagem , Rivaroxabana/administração & dosagem , Animais , Aspirina/administração & dosagem , Aterosclerose/patologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/farmacologia , Hemorragia/induzido quimicamente , Humanos , Rivaroxabana/efeitos adversos , Rivaroxabana/farmacologia , Prevenção Secundária/métodos
10.
Int J Oncol ; 55(1): 223-242, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180528

RESUMO

The aim of this study was to examine the effects of 5­fluorouracil (5­FU), anti­epidermal growth factor receptor (EGFR) antibody and aspirin (ASA) on the characteristics of two CRC cell lines, HCT116 and HT29, maintained in a spherical culture system. We observed that the morphology of both the HCT116 and HT29 cell­derived spheres was significantly impaired and the size of the colonospheres was markedly reduced following treatment with the aforementioned three drugs. In contrast to adherent cultures, the spherical cultures were more resistant to the tested drugs, as was reflected by their capacity to re­create the colonospheres when sustained in serum­free medium. Flow cytometric analysis of the drug­treated HCT116 cell­derived spheres revealed changes in the fraction of cells expressing markers of cancer stem cells (CSCs), whereas the CSC phenotype of HT29 cell­derived colonospheres was affected to a lesser extent. All reagents enhanced the percentage of non­viable cells in the colonospheres despite the diminished fraction of active caspase­3­positive cells following treatment of the HT29 cell­derived spheres with anti­EGFR antibody. Increased autophagy, assessed by acridine orange staining, was noted following the incubation of the HT29­colonospheres with ASA and 5­FU in comparison to the control. Notably, the percentage of cyclooxygenase (COX)­2­positive cells was not affected by ASA, although its activity was markedly elevated in the colonospheres incubated with anti­EGFR antibody. On the whole, the findings of this study indicate that all the tested drugs were involved in different cellular processes, which suggests that they should be considered for the combined therapeutic treatment of CRC, particularly for targeting the population of CSC­like cells. Thus, cancer cell­derived spheres may be used as a preferable model for in vitro anticancer drug testing.


Assuntos
Anticorpos Monoclonais/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Aspirina/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/farmacologia , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/imunologia , Aspirina/administração & dosagem , Autofagia/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Ciclo-Oxigenase 2/biossíntese , Ciclo-Oxigenase 2/metabolismo , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/imunologia , Proteína Ligante Fas/biossíntese , Fluoruracila/administração & dosagem , Células HCT116 , Células HT29 , Humanos , Esferoides Celulares , Receptor fas/biossíntese
11.
Gastroenterology ; 157(3): 682-691.e2, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31152740

RESUMO

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.


Assuntos
Aspirina/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Hemorragia Gastrointestinal/prevenção & controle , Pantoprazol/administração & dosagem , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Rivaroxabana/administração & dosagem , Idoso , Aspirina/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Método Duplo-Cego , Esquema de Medicação , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/microbiologia , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol/efeitos adversos , Doença Arterial Periférica/diagnóstico , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
12.
Int. j. morphol ; 37(2): 739-743, June 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1002287

RESUMO

La preeclampsia (PE) es un trastorno hipertensivo inducido por el embarazo donde se reduce la presión de la perfusión uterina. Investigaciones avalan el uso de dosis baja de aspirina (DBAAS) y su utilidad en la prevención de PE en gestantes con factores de riesgo. Sus beneficios en modelos animales sometidos a esta reduccción no están determinados. El objetivo de la investigación fue analizar la presión arterial sistémica y los hallazgos morfológicos a nivel renal en fetos de ratas con reducción de la presión de perfusión uterina (RPPU) expuestas a DBAAS en comparación a las no expuestas. Se conformaron cuatro grupos de ratas hembras preñadas Sprague Dawley (n=5). A los 14,5 días post-concepción (dpc), vía quirúrgica se indujo RPPU, ligando arterias uterinas, conformándose el grupo RPPU y el grupo RPPU+DBAAS al que se le administró 5 mg/kg/día de aspirina vía oral. El grupo control lo conformaron las no operadas y el grupo DBAAS se le administró aspirina en igual dosis desde el 14,5 dpc. A los 18,5 dpc, previo a la eutansia se midió la presión arterial sistémica con pletismógrafo caudal Insight v2.11 y se extrajeron los fetos. Se midió la longitud céfalo-caudal (LCC), se procesaron y tiñeron con hematoxilina-eosina, describiéndose cortes histológicos transversales a nivel renal. Se determinó que en la presión arterial media, hubo diferencias significativas entre el grupo RPPU y RPPU+DBAAS (p<0,05). El tamaño de los fetos fue menor en el grupo RPPU (p<0,0001), donde 1 feto presentó hernia umbilical congénita. La cuantificación de vesículas renales también fue menor (p<0,005). En conclusión, la administración de DBAAS disminuye los efectos inducidos por la RPPU en cuanto al tamaño fetal, morfología renal y malformaciones congénitas como hernia umbilical. En cuanto a la presión arterial sistémica, tendría efectos sólo en presión arterial media.


Preeclampsia (PE) is a hypertensive disorder induced by pregnancy where there is a reduction in the uterine perfusion pressure. Research supports the use of low dose aspirin (LDAAS) and its usefulness in the prevention of PE in pregnant women with risk factors. Their benefits in animal models subject to RUPP are not determined. The objective of the investigation was to analyze the systemic blood pressure and the morphological findings at renal level in fetuses of rats with reduction of uterine perfusion pressure (RUPP) exposed to LDAAS compared to those not exposed. Four groups of pregnant female rats Sprague Dawley (n=5) were formed. At 14.5 days post-conception (dpc), surgical RUPP was induced, ligating uterine arteries, with the RUPP group and RUPP+LDAAS group being given 5 mg/kg/day of aspirin orally. The control group was made up of those not operated and the LDAAS group was administered aspirin in the same dose from 14.5 dpc. A 18.5 dpc, prior to euthanasia systemic blood pressure was measured with flow plethysmograph Insight v2.11 and fetuses were extracted. The cephalo-caudal length (CCL) was measured, processed and stained with hematoxylin-eosin, describing transverse histological sections at the kidney level. It was determined that in the mean arterial pressure, there were significant differences between the group RUPP and RUPP+LDAAS (p <0.05). The size of the fetuses was lower in the RUPP group (p <0.0001), where one fetus presented congenital umbilical hernia. The quantification of renal vesicles was also lower (p <0.005). In conclusion, the administration of LDAAS decreases the effects induced by RUPP in terms of fetal size, renal morphology and congenital malformations such as umbilical hernia. Regarding the systemic blood pressure, effects would only mean arterial pressure.


Assuntos
Animais , Feminino , Gravidez , Ratos , Pressão Sanguínea/efeitos dos fármacos , Aspirina/administração & dosagem , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Perfusão , Fluxo Sanguíneo Regional , Útero/irrigação sanguínea , Aspirina/farmacologia , Estudos Prospectivos , Estudos Longitudinais , Ratos Sprague-Dawley , Feto , Pressão Arterial/efeitos dos fármacos
15.
HNO ; 67(8): 620-627, 2019 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-31069402

RESUMO

BACKGROUND: Analgesic intolerance (AI) is an important diagnostic feature of disease progression in patients with chronic rhinosinusitis (CRS) accompanied by nasal polyps (CRSwNP) and asthma. OBJECTIVE: The aim of the present study was to determine whether increasing the concentration of acetylsalicylic acid (ASA) used in the diagnostic nasal challenge would improve detection of ASA intolerance (NSAIDs-exacerbated respiratory disease, N­ERD). METHODS: Patients with CRSwNP, asthma, and with (CRSwNP-AAI, n = 20) or without (CRSwNP-A, n = 15) anamnestically reported AI, as well as control subjects with CRS but no nasal polyps, asthma, or AI (n = 15), were challenged nasally with 16 mg ASA and, in case of a negative result, with 25 mg of ASA. RESULTS: In CRSwNP-AAI subjects, the challenge with 16 mg ASA resulted in detection of AI in 80% of cases; increasing the challenge of ASA to 25 mg improved the AI detection to 95%. In CRSwNP-A subjects, the detection of AI increased from 40% (16 mg ASA) to 53% (25 mg ASA). In the control group, no reaction to nasal ASA challenge was detected. No difference in the diagnosis of positive reactions after provocation was found when using the German vs. the European recommended evaluation criteria. Mild pulmonary symptoms occurred in 2 (10%) CRSwNP-AAI patients following the 16 mg ASA challenge. CONCLUSION: In patients with CRSwNP, asthma, and anamnestic AI, nasal provocation can effectively confirm the diagnosis of N­ERD and can also be recommended for patients with recurrent CRSwNP and asthma but without reported AI. Increasing the ASA challenge to 25 mg increases the overall detection rate.


Assuntos
Aspirina/administração & dosagem , Asma Induzida por Aspirina/diagnóstico , Pólipos Nasais , Rinite , Sinusite , Anti-Inflamatórios não Esteroides , Aspirina/imunologia , Doença Crônica , Humanos , Pólipos Nasais/diagnóstico , Rinite/diagnóstico , Sinusite/diagnóstico
16.
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
17.
JAMA ; 321(17): 1686-1692, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31063574

RESUMO

Importance: Fecal immunochemical tests for hemoglobin are widely used for colorectal cancer (CRC) screening. Observational studies suggested that sensitivity of fecal immunochemical tests for detecting advanced neoplasms could be increased by acetylsalicylic acid (aspirin), especially among men. Objective: To evaluate the potential to increase sensitivity of fecal immunochemical tests by administering a single 300-mg oral aspirin dose 2 days before stool sampling. Design, Setting, and Participants: A randomized, placebo-controlled, double-blind trial was conducted in 14 gastroenterology practices and 4 hospitals in Germany, and included 2422 men and women aged 40 to 80 years scheduled for colonoscopy, with no recent use of aspirin or other drugs with antithrombotic effects (enrollment from June 2013 to November 2016, and final follow-up January 27, 2017). Interventions: Administration of a single tablet containing 300 mg of aspirin (n = 1208) or placebo (n = 1214) 2 days before fecal sampling for fecal immunochemical test. Main Outcome and Measures: The primary outcome was sensitivity of a quantitative fecal immunochemical test at 2 predefined cutoffs (10.2 and 17-µg Hb/g stool) for detecting advanced neoplasms (colorectal cancer or advanced adenoma). Results: Among 2422 randomized patients (mean [SD] age, 59.6 [7.9] years; 1219, 50%, men), 2134 were included in the analysis (78% for primary screening colonoscopy, 22% for diagnostic colonoscopy). Advanced neoplasms were identified in 224 participants (10.5%), including 8 participants (0.4%) with CRC and 216 participants (10.1%) with advanced adenoma. Sensitivity was 40.2% in the aspirin group and 30.4% in the placebo group (difference 9.8%, 95% CI, -3.1% to 22.2%, P = .14) at cutoff 10.2-µg Hb/g stool and 28.6% in the aspirin and 22.5% in the placebo group (difference 6.0%, 95% CI, -5.7% to 17.5%, P = .32) at cutoff 17-µg Hb/g stool. Conclusions and Relevance: Among adults aged 40 to 80 years not using aspirin or other antithrombotic medications, administration of a single dose of oral aspirin prior to fecal immunochemical testing, compared with placebo, did not significantly increase test sensitivity for detecting advanced colorectal neoplasms at 2 predefined cutoffs of a quantitative fecal immunochemical test. Trial registration: Deutsches Register Klinischer Studien Identifier: DRKS00003252; EudraCT Identifier: 2011-005603-32/DE.


Assuntos
Aspirina/administração & dosagem , Neoplasias Colorretais/diagnóstico , Sangue Oculto , Adenoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
18.
J Cancer Res Clin Oncol ; 145(7): 1795-1809, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31098750

RESUMO

BACKGROUND: In the United States, cancer is the second leading cause of mortality, and millions more battle cancer worldwide. As such, primary prevention of cancer is a major interest globally. Aspirin has been studied as a primary prevention method for multiple diseases, mainly cardiovascular disease and various forms of cancer. The role of aspirin as a primary prevention of cancer is still controversial and may be more beneficial in certain cancers over others. With rapidly surfacing large randomized controlled trials (RCTs) studying this subject, we aimed to evaluate the efficacy and safety of aspirin as a primary prophylaxis for cancer. METHODS: A comprehensive electronic database search was conducted for all RCTs that compared aspirin versus placebo for the prevention of any type of disease, and where cancer incidence or mortality was reported. The primary outcome was cancerrelated mortality. Secondary outcomes were cancer incidence, all-cause mortality, major bleeding, any bleeding and gastrointestinal (GI) bleeding. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model at the longest follow-up period. RESULTS: We included 16 RCTs with 104,018 total patients, mean age of 60.51 years, mean follow-up of 5.48 years, and a male percentage of 38.72%. We found that aspirin was not associated with a significant reduction of cancer-related mortality compared with placebo (RR 0.99; 95% CI: 0.87-1.12; P = 0.85: I2 = 41%). Compared with placebo, aspirin was not associated with significant reduction of all-cause mortality (RR 0.97; 95% CI: 0.92-1.02; P = 0.19; I2 = 13%) or cancer incidence (RR: 0.98; 95% CI: 0.92-1.04; P = 0.43; I2 = 16%). However, aspirin treatment was associated with significantly increased risks of any bleeding (RR 1.63; 95% CI: 1.31-2.03; P < 0.01), major bleeding (RR 1.41; 95% CI: 1.26-1.57; P < 0.01), and GI bleeding (RR 1.85; 95% CI: 1.38-2.48; P < 0.01) compared with placebo. CONCLUSION: Our study did not find any significant reductions in cancer-related mortality or cancer incidence when compared aspirin use with placebo or no aspirin. Our study also highlights that the use of aspirin for primary prevention of cancer was found to cause higher rates of bleeding (any bleeding, major bleeding, and GI bleeding) compared to placebo or no aspirin at the longest follow-up period with no significant benefit in cancer primary prevention.


Assuntos
Aspirina/administração & dosagem , Aspirina/efeitos adversos , Neoplasias/prevenção & controle , Humanos , Neoplasias/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
N Engl J Med ; 380(20): 1906-1917, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-31091372

RESUMO

BACKGROUND: Cryptogenic strokes constitute 20 to 30% of ischemic strokes, and most cryptogenic strokes are considered to be embolic and of undetermined source. An earlier randomized trial showed that rivaroxaban is no more effective than aspirin in preventing recurrent stroke after a presumed embolic stroke from an undetermined source. Whether dabigatran would be effective in preventing recurrent strokes after this type of stroke was unclear. METHODS: We conducted a multicenter, randomized, double-blind trial of dabigatran at a dose of 150 mg or 110 mg twice daily as compared with aspirin at a dose of 100 mg once daily in patients who had had an embolic stroke of undetermined source. The primary outcome was recurrent stroke. The primary safety outcome was major bleeding. RESULTS: A total of 5390 patients were enrolled at 564 sites and were randomly assigned to receive dabigatran (2695 patients) or aspirin (2695 patients). During a median follow-up of 19 months, recurrent strokes occurred in 177 patients (6.6%) in the dabigatran group (4.1% per year) and in 207 patients (7.7%) in the aspirin group (4.8% per year) (hazard ratio, 0.85; 95% confidence interval [CI], 0.69 to 1.03; P = 0.10). Ischemic strokes occurred in 172 patients (4.0% per year) and 203 patients (4.7% per year), respectively (hazard ratio, 0.84; 95% CI, 0.68 to 1.03). Major bleeding occurred in 77 patients (1.7% per year) in the dabigatran group and in 64 patients (1.4% per year) in the aspirin group (hazard ratio, 1.19; 95% CI, 0.85 to 1.66). Clinically relevant nonmajor bleeding occurred in 70 patients (1.6% per year) and 41 patients (0.9% per year), respectively. CONCLUSIONS: In patients with a recent history of embolic stroke of undetermined source, dabigatran was not superior to aspirin in preventing recurrent stroke. The incidence of major bleeding was not greater in the dabigatran group than in the aspirin group, but there were more clinically relevant nonmajor bleeding events in the dabigatran group. (Funded by Boehringer Ingelheim; RE-SPECT ESUS ClinicalTrials.gov number, NCT02239120.).


Assuntos
Antitrombinas/administração & dosagem , Dabigatrana/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Idoso , Antitrombinas/efeitos adversos , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Dabigatrana/efeitos adversos , Método Duplo-Cego , Feminino , Hemorragia/induzido quimicamente , Humanos , Incidência , Embolia Intracraniana/tratamento farmacológico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Recidiva , Prevenção Secundária , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 217: 176-181, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30933782

RESUMO

The morbidity of coronary heart disease (CHD) with high risks has been rising in recent years. A novel and noninvasive method based on surface-enhanced Raman spectroscopy (SERS) was proposed by Yang et al. (Analyst 143: 2235, 2018) to prospectively diagnose the arterial blockage by detecting platelet-derived growth factor-BB (PDGF-BB) in urine. Clinically, anti-platelet drugs (such as aspirin, statins and clopidogrel) are often used for ordinary CHD patients or patients with percutaneous coronary intervention (PCI). Therefore, whether the previous developed method can be applied to the CHD patients on long-term medication (more than 6 months) or post-PCI patients was investigated here. Firstly, urine samples of 13 CHD patients on long-term medication (aspirin, rosuvastatin, clopidogrel bisulfate) and 13 post-PCI patients were measured by the proposed method. Clinical data of coronary angiography results provided by Xin Hua Hospital and Yangpu District Central Hospital Antu Branch revealed that these 26 patients were with serious arterial blockage, however, characteristic Raman peak at 1509 cm-1 attributed to PDGF-BB was not observed in the SERS spectra of these 26 patients. In addition, an eight-day follow-up investigation was performed on a CHD patient with PCI three years ago and on long-term medication. It was found that the Raman peak at 1509 cm-1 could be only observed in the third and fourth day after suspending the drugs. Furthermore, SERS spectra of mixed solutions of PDGF-BB and aspirin, rosuvastatin, mixed solutions of these two drugs and clopidogrel bisulfate were analyzed. The Raman peak at 1509 cm-1 was not found in all these spectra, it indicated that all the three kinds of drugs could influence on the SERS signal of PDGF-BB. Therefore, the previous developed method is not suitable for CHD patients on long-term medication and post-PCI patients.


Assuntos
Becaplermina/urina , Doença das Coronárias/diagnóstico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/administração & dosagem , Análise Espectral Raman/métodos , Aspirina/administração & dosagem , Becaplermina/efeitos dos fármacos , Clopidogrel/administração & dosagem , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/urina , Humanos , Estudos Prospectivos
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