RESUMO
AIM: The aim of this preliminary study was to detect cytological changes in the oral mucosa after using a mouth wash with alcohol. MATERIAL AND METHODS: A prospective double-blind, controlled study was performed, for 6 months. Group 1 consisted of 30 subjects who used a mouth rinse with 26.9% of alcohol [Listerine] and Group 2 consisted of 30 subjects who used a mouth rinse with the same ingredients but with no alcohol. We obtained three cytological samples from the oral mucosa. The presence of cytological atypia, binucleation and karyorrhesis, and type of cells were studied. We also used a fluorescent in situ hybridization technique (FISH) in 15 samples in each group, for the micronucleus. RESULTS: We found no clinical mucosal alteration after using the mouth wash at the end of the study in either group. We observed no cytological differences between the groups at the end of the study (p>0.05). Regarding the study of the micronucleus by FISH, we observed no significant difference between the groups (p>0.05). CONCLUSIONS: Our results showed no cytological alteration in patients using a mouth rinse with alcohol, but these findings should be considered preliminary results, to be confirmed in a greater sample of patients.
Assuntos
Etanol/farmacologia , Mucosa Bucal/citologia , Mucosa Bucal/efeitos dos fármacos , Antissépticos Bucais/farmacologia , Salicilatos/farmacologia , Terpenos/farmacologia , Adulto , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Estudos ProspectivosRESUMO
Aim: To assess the cost-effectiveness of first-line treatment with dacomitinib compared with gefitinib in patients newly diagnosed with advanced NSCLC EGFR-positive in the context of Spain. Materials & methods: A partitioned survival model was developed including costs, utilities and disutilities to estimate quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio when treating with dacomitinib versus gefitinib. Results: Dacomitinib presented higher QALYs (0.51) compared with gefitinib (0.45). Dacomitinib costs were 33,061 in comparison with 26,692 for gefitinib arm. An incremental cost-effectiveness ratio of 111,048 was obtained for dacomitinib. Conclusion: Dacomitinib was more effective in terms of QALYs gained than gefitinib. However, to obtain a cost-effectiveness alternative, a discount greater than 25% in dacomitinib acquisition cost is required.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Análise Custo-Benefício , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Anos de Vida Ajustados por Qualidade de Vida , Quinazolinonas , EspanhaRESUMO
Aim: Osimertinib improves progression-free survival in first-line EGFR mutation-positive non-small-cell lung cancer. Materials & methods: A Markov cohort model including costs, utilities and disutilities, was conducted to estimate quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio when treating with osimertinib versus standard first-line tyrosine kinase inhibitors (TKIs). Results: Osimertinib presented higher QALYs (0.61) compared with standard EGFR-TKIs (0.42). Osimertinib costs were 83,258.99, in comparison with 29,209.45 for the standard EGFR-TKIs. An incremental cost-effectiveness ratio of 273,895.36/QALY was obtained for osimertinib. Conclusion: Osimertinib was more effective in terms of QALYs gained than comparators (erlotinib-gefitinib). However, to obtain a cost-effectiveness alternative, a discount greater than 60% in osimertinib acquisition cost is required.
Assuntos
Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Acrilamidas/economia , Compostos de Anilina/economia , Antineoplásicos/economia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Análise Custo-Benefício , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/mortalidade , Cadeias de Markov , Modelos Econométricos , Mutação , Inibidores de Proteínas Quinases/economia , Inibidores de Proteínas Quinases/uso terapêutico , Anos de Vida Ajustados por Qualidade de VidaRESUMO
Cardiopulmonary bypass (CPB) is associated with oxidative stress. This study examined antioxidant levels in adults undergoing CPB surgery and their correlation with clinical variables. Arterial blood samples were obtained from 27 patients undergoing CPB. The time-course variation of vitamin C (spectrofluorimetry), alpha-tocopherol and retinol (HPLC) levels were determined. Plasma vitamin C rose initially but gradually decayed during reperfusion until 60% reduction of baseline values post-surgery. alpha-Tocopherol and retinol were reduced along CPB with post-operative values approximately 25% lower than baseline. No significant changes were found for selenium and glutathione peroxidase. PaO(2) values rose steadily throughout CPB. A correlation existed for alpha-tocopherol and retinol depletion vs maximal PaO(2) throughout CPB but no correlation was found for antioxidant consumption vs duration of ischaemia and reperfusion and hypothermia level. In conclusion, consumption of arterial blood antioxidant vitamins occurs with CPB in relation with PaO(2) levels but not for other clinical variables measured in this study.
Assuntos
Antioxidantes/análise , Ponte Cardiopulmonar , Estresse Oxidativo , Oxigênio/sangue , Vitamina A/sangue , alfa-Tocoferol/sangue , Idoso , Ácido Ascórbico/sangue , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão ParcialRESUMO
BACKGROUND AND AIMS: This study sought to determine the prevalence of malnutrition in patients with inflammatory bowel disease, to analyse the dietary beliefs and behaviours of these patients, to study their body composition, to evaluate their muscular strength and to identify the factors associated with malnutrition in these patients. METHODS: This was a prospective, multicentre study. Crohn's disease and ulcerative colitis patients from 30 Spanish centres, from the outpatient clinics, were included. A questionnaire of 11 items was applied to obtain data from patients' dietary behaviour and beliefs. Patients who accepted were evaluated to assess their nutritional status using Subjective Global Assessment and body mass index. Body composition was evaluated through bioelectrical impedance. RESULTS: A total of 1271 patients were included [51% women, median age 45 years, 60% Crohn's disease]. Of these, 333 patients underwent the nutritional evaluation. A total of 77% of patients declared that they avoided some foods to prevent disease relapse. Eighty-six per cent of patients avoided some foods when they had disease activity because of fear of worsening the flare. Sixty-seven per cent of patients modified their dietary habits after disease diagnosis. The prevalence of malnutrition was 16% [95% confidence interval = 12-20%]. In the multivariate analysis, history of abdominal surgery, active disease and avoidance of some foods during flares were associated with higher risk of malnutrition. CONCLUSIONS: The prevalence of malnutrition in inflammatory bowel disease patients was high. We identified some predictive factors of malnutrition. Most of the patients had self-imposed food restrictions, based on their beliefs.
Assuntos
Dieta , Comportamento Alimentar , Conhecimentos, Atitudes e Prática em Saúde , Doenças Inflamatórias Intestinais/fisiopatologia , Desnutrição/epidemiologia , Desnutrição/fisiopatologia , Estado Nutricional , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Índice de Massa Corporal , Doença de Crohn , Impedância Elétrica , Feminino , Alimentos , Força da Mão , Humanos , Doenças Inflamatórias Intestinais/complicações , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Prevalência , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Exacerbação dos Sintomas , Adulto JovemRESUMO
BACKGROUND: Infection remains a drawback of parenteral nutrition (PN), probably related, among other factors, to immunosuppressive effects of its lipid component. Newer preparations may have lesser immunosuppressive impact. This study examines the effects of an olive oil-based lipid emulsion (long-chain triacylglycerols-monounsaturated fatty acids [LCT-MUFA]; ClinOleic) on various functions of human neutrophils in vitro and on rat leukocyte-endothelial cell interactions in vivo compared with LCT (Intralipid) and 50% LCT-50% medium-chain triacylglycerols (MCT; Lipofundin) mixture. METHODS: Neutrophils isolated from healthy donors were incubated with concentrations (0.03-3 mmol/L) of lipid emulsions encompassing clinically relevant levels. In vivo leukocyte recruitment was studied with intravital microscopy within rat mesenteric microcirculation. RESULTS: LCT-MUFA (3 mmol/L) did not alter the N-formyl-Met-Leu-Phe (FMLP)-induced rise in [Ca2+]i, oxidative burst, chemotaxis, and elastase release, whereas LCT-MCT decreased [Ca2+]i and chemotaxis and increased oxidative burst. FMLP-induced LTB4 production was augmented by lipid emulsions. Serum-opsonized zymosan-induced phagocytosis was unaltered by lipid emulsions. Basal and FMLP-induced CD11b expression was unaffected by lipid emulsions. Lipopolysaccharide (LPS)-induced TNF-alpha, IL-1beta and IL-8 mRNA, and protein expression was unaltered by LCT-MUFA, whereas LCT and LCT-MCT decreased IL-1beta mRNA and protein. LCT-MUFA did not alter apoptosis, but LCT increased apoptosis in absence and presence of GM-CSF. LPS (1 microg/mL)-induced increase in leukocyte rolling flux, adhesion, and emigration was inhibited by LCT and LCT-MCT but unaffected in LCT-MUFA-treated rats. Immunohistochemistry showed LPS-induced increase in P-selectin expression attenuated by LCT and LCT-MCT but not LCT-MUFA. CONCLUSIONS: LCT-MUFA showed lower in vitro and in vivo impact on neutrophil function compared with LCT and LCT-MCT.
Assuntos
Cálcio/metabolismo , Quimiotaxia/efeitos dos fármacos , Emulsões Gordurosas Intravenosas/farmacologia , Leucócitos/fisiologia , Neutrófilos/fisiologia , Óleos de Plantas , Explosão Respiratória/efeitos dos fármacos , Animais , Células Cultivadas , Quimiotaxia/fisiologia , Relação Dose-Resposta a Droga , Células Endoteliais/imunologia , Humanos , Masculino , Azeite de Oliva , Ratos , Ratos Sprague-Dawley , Explosão Respiratória/fisiologiaRESUMO
PURPOSE: Tacrolimus ocular preparations are commonly employed in autoimmune or inflammatory ocular disorders. However, currently there are not yet approved ocular formulations. Tacrolimus ocular side effects have been reported in clinical use, so the evaluation of different pharmaceutical preparations is mandatory. In this study, the local corneal tolerance and safety profile of three common tacrolimus 0.03% pharmaceutical preparations were evaluated. MATERIAL AND METHODS: Corneal irritation and permeability of tacrolimus preparations were evaluated with the bovine corneal opacity and permeability (BCOP) test. Complementary corneal hematoxylin/eosin and immunohistochemistry staining for tight junctions and adherent junctions E-cadherin, VE-cadherin and zonula occludens-1 were examined and scored to evaluate and to confirm corneal disruption and irritation scores obtained with the BCOP method. RESULTS: Commercial brand ointment (Protopic®), topical compounded eye ointment (pharmacy elaboration) and tacrolimus suspension eye drops (elaborated from parenteral prograf®) were tested as potential ocular preparations to be used in clinics. Tacrolimus preparations hereby studied do not alter the opacity and permeability of the bovine cornea by more than three units, measured by the In Vitro Irritancy Score, neither affected the immunohistochemical parameters, composite score or transepithelial electrical resistance. CONCLUSIONS: Tacrolimus preparations studied can be safely applied as a topical ocular treatment.
Assuntos
Córnea/metabolismo , Opacidade da Córnea/tratamento farmacológico , Tacrolimo/administração & dosagem , Animais , Bovinos , Córnea/efeitos dos fármacos , Opacidade da Córnea/induzido quimicamente , Opacidade da Córnea/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Imuno-Histoquímica , Imunossupressores/administração & dosagem , Irritantes/toxicidade , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/farmacocinética , Permeabilidade/efeitos dos fármacos , Tacrolimo/farmacocinéticaRESUMO
The alteration of vancomycin pharmacokinetics during cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery was studied. Eighteen patients were enrolled in the study. Vancomycin (1 g) was intravenously infused one to two hours before surgery. Blood samples were taken before, during, and after CPB. Serum drug concentrations were determined by an automated fluorescence polarization immunoassay and adjusted, with a bayesian analysis, to a bi-compartmental model implemented in a pharmacokinetic system program. Serum creatinine, hematocrit, and plasma proteins were also measured before, during, and after CPB. During CPB, serum creatinine, hematocrit, and plasma protein values all decreased significantly (p < 0.05). Serum vancomycin concentration also diminished abruptly with CPB (7.04 micrograms/mL; 95% confidence interval, 5.70-8.38 micrograms/mL) but increased moderately during the next 30 minutes, probably attributable to redistribution into plasma from tissue stores. Vancomycin's apparent volume of distribution showed an important increase during CPB (58.8%) (p < 0.0005), and its systemic clearance also increased significantly after CPB (19.7%) (p < 0.0005). The decrease in serum vancomycin concentration seems mediated by the hemodilution associated with the pump prime volume. Vancomycin's mean +/- S.D. nadir serum concentration before the next dose was 7.13 +/- 2.1 micrograms/mL. In patients undergoing cardiac surgery and treated prophylactically with a 1-g preoperative i.v. dose of vancomycin, the onset of CPB was associated with a drop in serum vancomycin concentration.
Assuntos
Ponte Cardiopulmonar , Vancomicina/farmacocinética , Adulto , Idoso , Antibacterianos/sangue , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Feminino , Meia-Vida , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Fatores de Tempo , Vancomicina/sangue , Vancomicina/uso terapêuticoRESUMO
Home parenteral nutrition (PN) is associated with many complications including severe hepatobiliary dysfunction. Commercial ω-6 fatty acid-soybean based-lipid emulsions in PN may mediate long term PN associate liver disease (PNALD) whereas ω-3-fish oil parenteral emulsions have shown to reverse PNALD in children. However, its clinical effectiveness in adults has been scarcely reported. In this work, we study the role of soybean and fish oil lipid commercial emulsions on inflammatory and profibrotic liver markers in adults with long term PNALD and in in vitro cellular models. Inflammatory and profibrotic markers were measured in serum of ten adults with long term PNALD and in culture supernatants of monocytes. Liver epithelial to mesenchymal transition (EMT) was induced by transforming growth factor beta 1 (TGFß1) to evaluate in vitro liver fibrosis. Omegaven®, a 100% fish oil commercial emulsion, was infused during four months in two patients with severe long term PNALD reversing, at the first month, the inflammatory, profibrotic and clinical parameters of PNALD. The effect was maintained during the treatment course but impaired when conventional lipid emulsions were reintroduced. The other patients under chronic soybean oil-based PN showed elevated inflammatory and profibrotic parameters. In vitro human monocytes stimulated with lipopolysaccharide induced a strong inflammatory response that was suppressed by Omegaven®, but increased by soybean emulsions. In other experiments, TGFß1 induced EMT that was suppressed by Omegaven® and enhanced by soybean oil lipid emulsions. Omegaven® improves clinical, anti-inflammatory and anti-fibrotic parameters in adults with long-term home PNALD.
Assuntos
Anti-Inflamatórios/administração & dosagem , Cicatriz/prevenção & controle , Emulsões Gordurosas Intravenosas/administração & dosagem , Óleos de Peixe/administração & dosagem , Hepatopatias/tratamento farmacológico , Nutrição Parenteral no Domicílio/efeitos adversos , Adulto , Idoso , Técnicas de Cultura de Células , Cicatriz/tratamento farmacológico , Transição Epitelial-Mesenquimal , Ácidos Graxos Ômega-6/administração & dosagem , Feminino , Humanos , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral no Domicílio/métodos , Óleo de Soja/administração & dosagem , TriglicerídeosAssuntos
Antipsicóticos/efeitos adversos , Creatina Quinase/sangue , Pirenzepina/análogos & derivados , Pirenzepina/efeitos adversos , Adulto , Antipsicóticos/farmacologia , Benzodiazepinas , Creatina Quinase Forma MB , Diagnóstico Diferencial , Humanos , Isoenzimas/sangue , Masculino , Pessoa de Meia-Idade , Síndrome Maligna Neuroléptica/sangue , Síndrome Maligna Neuroléptica/diagnóstico , Síndrome Maligna Neuroléptica/enzimologia , Olanzapina , Pirenzepina/farmacologia , Estimulação QuímicaAssuntos
Esclerose Lateral Amiotrófica/fisiopatologia , Toxinas Botulínicas Tipo A/administração & dosagem , Neurotoxinas/administração & dosagem , Sialorreia/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Nutrição Enteral , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Sialorreia/etiologia , Glândula Submandibular , Resultado do TratamentoRESUMO
Aim: The aim of this preliminary study was to detect cytological changes in the oral mucosa after using a mouth wash with alcohol. Material and Methods: A prospective double-blind, controlled study was performed, for 6 months. Group 1 consisted of 30 subjects who used a mouth rinse with 26.9% of alcohol [Listerine(R)] and Group 2 consisted of 30 subjects who used a mouth rinse with the same ingredients but with no alcohol. We obtained three cytological samples from the oral mucosa. The presence of cytological atypia, binucleation and karyorrhesis, and type of cells were studied. We also used a fluorescent in situ hybridization technique (FISH) in 15 samples in each group, for the micronucleus. Results: We found no clinical mucosal alteration after using the mouth wash at the end of the study in either group. We observed no cytological differences between the groups at the end of the study (p>0.05). Regarding the study of the micronucleus by FISH, we observed no significant difference between the groups (p>0.05). Conclusions: Our results showed no cytological alteration in patients using a mouth rinse with alcohol, but these findings should be considered preliminary results, to be confirmed in a greater sample of patients (AU)
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