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The aim of this work was to develop, for the first time, sustainable strategies, based on the use of Ultrasound-Assisted Extraction, Natural Deep Eutectic Solvents, and Pressurized Liquid Extraction, to extract proteins from lime (Citrus x latifolia) peels and to evaluate their potential to release bioactive peptides. PLE showed the largest extraction of proteins (66-69%), which were hydrolysed using three different enzymes (Alcalase 2.4 L FG, Alcalase®PURE 2.4 L, and Thermolysin). The in vitro antioxidant and antihypertensive activities of released peptides were evaluated. Although all hydrolysates showed antioxidant and antihypertensive activity, the hydrolysate obtained with Thermolysin showed the most significant values. Since the Total Phenolic Content in all hydrolysates was low, peptides were likely the main contributors to these bioactivities. Hydrolysates were analyzed by UHPLC-QTOF-MS and a total of 98 different peptides were identified. Most of these peptides were rich in amino acids associated with antioxidant activity.
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Academic procrastination is a persistent behavior in students' academic development consisting of postponing or delaying the completion of necessary tasks and having a deadline for completion, which is associated with detriment in performance, school dropout, and loss of student well-being. The largest body of existing knowledge on this behavior comes from studies conducted with university students, although it is necessary to deepen the findings obtained at lower educational levels. The aim of this work has been to carry out a scoping review of the empirical publications focused on academic procrastination in children and adolescents. The inclusion and exclusion criteria are detailed following the general guidelines of the Joanna Briggs Institute. However, some modifications are incorporated in the flowchart to guide the review sequence. The search was conducted in eleven thematic (ERIC, MedLine, Psychology and Behavioral Sciences Collection, PsycINFO, PubPsych, and Teacher Reference Center) and multidisciplinary databases (Academic Search Ultimate, E-Journals, ProQuest, Scopus, and Web of Science) to identify relevant publications up to 2022, including grey literature. Out of the initial 1185 records screened, a total of 79 records were selected. The search results included a total of 79 records. The most used assessment instruments, the most studied variables, and the type of design and sources of information used in the selected studies are detailed. Cultural aspects that open new lines of future research are identified.
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Academic procrastination is a complex behavior that hampers the cyclical process of self-regulation in learning, impeding the flow of actions necessary to achieve the goals and sub-goals that students have set out to attain. It has a high frequency of occurrence and has been linked to lessened student performance and a decrease in psychological and physical well-being. The objective of this study is to analyze the psychometric characteristics of a new academic procrastination scale MAPS-15 (Multidimensional Academic Procrastination Scale) applicable in self-regulated learning environments through a cross-validation study (exploratory factor analysis and confirmatory factor analysis). The sample consisted of 1289 students from a distance/online university, with a wide age range and sociocultural variability. The students completed self-reported online questionnaires on two dates: during the university access and adaptation phase and before the first period of compulsory exams. One-, two- and three-factor structures were tested as well as a second-order structure. The results support a three-dimensional structure of MAPS-15: core procrastination, a pure dimension of procrastinating behavior and difficulty in carrying out the action; poor time management, a dimension related to time organization and perceived control over time; and work disconnection, a dimension conceptually related to lack of persistence, and work interruptions.
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Procrastinação , Humanos , Estudantes/psicologia , Aprendizagem , Psicometria , AutorrelatoRESUMO
BACKGROUND: Despite the scarce evidence, some studies suggest that cross-level clinical coordination may vary among secondary care (SC) doctors, influenced by their speciality and organisational model, including degree of decentralisation to primary care (PC). The aim was to determine the differences in experience and perception of cross-level clinical coordination and related factors according to the SC doctor's speciality in the Catalan health system. METHODS: Cross-sectional study, based on an on-line survey using the COORDENA-CAT questionnaire, to SC doctors (n = 1666). Descriptive and multivariate analysis were used to compare five groups of SC specialities (decentralised, hospital-based, internists/geriatricians, gynaecologist, and paediatricians), for experience, perception and factors related to coordination. RESULTS: When comparing with decentralised specialities, hospital-based specialities and internal medicine/geriatrics reported lower care consistency and follow up across levels, while gynaecology and paediatrics, higher accessibility. General perception of cross-level coordination was lower in hospital-based specialities (PR:0.80, 95% CI 0.72-0.89) and higher in gynaecology (PR:1.36, 95% CI 1.18-1.56). Moreover, hospital-based specialities reported a lower use of some coordination mechanisms and lower knowledge of the primary care doctors (PR:0.42, 95% CI 0.23-0.72), while gynaecology a higher knowledge (PR:2.04, 95% CI 1.22-3.45). CONCLUSIONS: Results show differences in experience, perception of coordination, organisational and interactional factors across specialities. These differences may be explained by their complexity, coordination needs and organisational model. Further research is needed to clarify and understand the causes of such differences and the particular needs of coordination of each speciality to identify strategies to improve cross-level clinical coordination.
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Ginecologia , Médicos , Humanos , Criança , Atenção Secundária à Saúde/métodos , Estudos Transversais , Medicina InternaAssuntos
Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Insuficiência da Valva Mitral , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVE: To analyze the experience and perception of clinical coordination across care levels and doctor's organizational and interactional related factors, according to the type of management integration of the healthcare services of the area, in Catalonia. METHOD: Cross-sectional study based on an online survey by self-administration of the questionnaire COORDENA-CAT. DATA COLLECTION: October-December 2017. STUDY POPULATION: primary and secondary care (acute and long-term care) doctors of the public Catalan health system. SAMPLE: 3308 doctors. OUTCOME VARIABLES: experience and perception of clinical coordination, knowledge and use of coordination mechanisms and organizational and interactional factors; explanatory variables: area according to type of management (integrated, semi-integrated, non-integrated), socio-demographic, employment characteristics and attitude toward work. Descriptive analysis by type of area and multivariate analysis by robust Poisson regression. RESULTS: Better clinical coordination was observed in integrated areas compared to those semi-integrated, mainly in relation to information transfer, adequate follow-up and perception of coordination in the area. No differences were found between integrated and non-integrated areas in the clinical coordination experience, although there were differences in perception and some related factors. There are common problems across areas, such as accessibility to secondary care. CONCLUSIONS: Few differences were found between integrated and non-integrated areas, revealing that management integration may facilitate clinical coordination but is not enough. Differences with semi-integrated areas indicate the need to promote cooperation formulas between all the providers of the territory, with common objectives and coordination mechanisms, in order to avoid inequalities in quality of care.
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Médicos , Atenção Secundária à Saúde , Estudos Transversais , Humanos , Espanha , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The resting full-cycle ratio (RFR) is a novel resting index which in contrast to the gold standard (fractional flow reserve (FFR)) does not require maximum hyperemia induction. The objectives of this study were to evaluate the agreement between RFR and FFR with the currently recommended thresholds and to design a hybrid RFR-FFR ischemia detection strategy, allowing a reduction of coronary vasodilator use. MATERIALS AND METHODS: Patients subjected to invasive physiological study in 9 Spanish centers were prospectively recruited between April 2019 and March 2020. Sensitivity and specificity studies were made to assess diagnostic accuracy between the recommended levels of RFR ≤0.89 and FFR ≤0.80 (primary objective) and to determine the RFR "grey zone" in order to define a hybrid strategy with FFR affording 95% global agreement compared with FFR alone (secondary objective). RESULTS: A total of 380 lesions were evaluated in 311 patients. Significant correlation was observed (R 2 = 0.81; P < 0.001) between the two techniques, with 79% agreement between RFR ≤ 0.89 and FFR ≤ 0.80 (positive predictive value, 68%, and negative predictive value, 80%). The hybrid RFR-FFR strategy, administering only adenosine in the "grey zone" (RFR: 0.86 to 0.92), exhibited an agreement of over 95% with FFR, with high predictive values (positive predictive value, 91%, and negative predictive value, 92%), reducing the need for vasodilators by 58%. CONCLUSIONS: Dichotomous agreement between RFR and FFR with the recommended thresholds is significant but limited. The adoption of a hybrid RFR-FFR strategy affords very high agreement, with minimization of vasodilator use.
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Adenosina/farmacologia , Angiografia Coronária/métodos , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Hiperemia , Isquemia Miocárdica , Idoso , Circulação Coronária/efeitos dos fármacos , Estenose Coronária/diagnóstico , Estenose Coronária/epidemiologia , Estenose Coronária/fisiopatologia , Correlação de Dados , Relação Dose-Resposta a Droga , Feminino , Humanos , Hiperemia/induzido quimicamente , Hiperemia/fisiopatologia , Masculino , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/fisiopatologia , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Espanha/epidemiologia , Vasodilatadores/farmacologiaRESUMO
Malignant hyperthermia is an hypermetabolic syndrome in which the intracellular calcium receptors are altered. Patients who present compatible symptoms with this symdrome are genetically predisposed. Many of the cases have been described in the surgical area, due to the use of anesthesic drugs and neuromuscular blockers. However, there are some cases with an unknown trigger. The prevalence of the syndrome is very difficult to estimate. The diagnosis and early treatment are pronostic factors predicting the evolution of the syndrome.
La hipertermia maligna es conocida como un síndrome de estimulación masiva del metabolismo, debido a la alteración en la liberación de calcio intracelular. Muchos pacientes que presentan clínica compatible con este síndrome están genéticamente predispuestos. La mayoría de los casos se describen en el ámbito quirúrgico, con el empleo de fármacos anestésicos y determinados relajantes neuromusculares, aunque también existen casos en los que no se halla desencadenante. De prevalencia difícil de estimar, la sospecha diagnóstica y el tratamiento precoz marcan el pronóstico evolutivo de estos pacientes.
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Humanos , Feminino , Pessoa de Meia-Idade , Apendicectomia , Anestésicos Inalatórios/efeitos adversos , Desflurano/efeitos adversos , Hipertermia Maligna/etiologia , Laparoscopia , Dantroleno/uso terapêutico , Hipertermia Maligna/diagnóstico , Hipertermia Maligna/tratamento farmacológicoRESUMO
The aim of this study was to analyze social networks' information about the anti-vaccine movement. A systematic review was performed in PubMed, Scopus, CINAHL and CUIDEN databases. The search equations were: "vaccine AND social network" and "vaccine AND (Facebook[title] OR Twitter[title] OR Instagram[title] OR YouTube[title])". The final sample was n = 12, including only articles published in the last 10 years, in English or Spanish. Social networks are used by the anti-vaccine groups to disseminate their information. To do this, these groups use different methods, including bots and trolls that generate anti-vaccination messages and spread quickly. In addition, the arguments that they use focus on possible harmful effects and the distrust of pharmaceuticals, promoting the use of social networks as a resource for finding health-related information. The anti-vaccine groups are able to use social networks and their resources to increase their number and do so through controversial arguments, such as the economic benefit of pharmaceuticals or personal stories of children to move the population without using reliable or evidence-based content.
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Movimento contra Vacinação , Mídias Sociais , Rede Social , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , VacinaçãoRESUMO
BACKGROUND: Clinical coordination across care levels is a priority for health systems around the world, especially for those based on primary health care. The aim of this study is to analyse the degree of clinical information and clinical management coordination across healthcare levels in the Catalan national health system experienced by primary (PC) and secondary care (SC) doctors and explore the associated factors. METHODS: Cross-sectional study based on an online survey using the self-administered questionnaire COORDENA-CAT. DATA COLLECTION: October-December 2017. STUDY POPULATION: PC and SC (acute and long term) doctors of the Catalan national health system. Participation rate was 21%, with a sample of 3308 doctors. OUTCOME VARIABLES: cross-level clinical information coordination, clinical management coordination, and perception of cross-level coordination within the area. Explanatory variables: socio-demographic, employment characteristics, attitude towards job, type of area (according to type of hospital and management), interactional factors, organizational factors and knowledge of existing coordination mechanisms. Stratification variable: level of care. Descriptive and multivariate analysis by logistic regression. RESULTS: The degree of clinical coordination experienced across levels of care was high for both PC and SC doctors, although PC doctors experienced greater exchange and use of information and SC doctors experienced greater consistency of care. However, only 32.13% of PC and 35.72% of SC doctors found that patient care was coordinated across care levels within their area. In both levels of care, knowing the doctors of the other level, working in an area where the same entity manages SC and majority of PC, and holding joint clinical case conferences were factors positively associated with perceiving high levels of clinical coordination. Other associated factors were specific to the care level, such as being informed of a patient's discharge from hospital for PC doctors, or trusting in the clinical skills of the other care level for SC doctors. CONCLUSIONS: Interactional and organizational factors are positively associated with perceiving high levels of clinical coordination. Introducing policies to enhance such factors can foster clinical coordination between different health care levels. The COORDENA questionnaire allows us to identify fields for improvement in clinical coordination.
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Atitude do Pessoal de Saúde , Continuidade da Assistência ao Paciente/organização & administração , Comunicação Interdisciplinar , Atenção Primária à Saúde , Atenção Secundária à Saúde , Percepção Social , Adulto , Estudos Transversais , Atenção à Saúde/organização & administração , Atenção à Saúde/tendências , Feminino , Humanos , Disseminação de Informação/métodos , Masculino , Informática Médica/métodos , Informática Médica/tendências , Pessoa de Meia-Idade , Atenção Primária à Saúde/métodos , Atenção Primária à Saúde/organização & administração , Pesquisa Qualitativa , Atenção Secundária à Saúde/métodos , Atenção Secundária à Saúde/organização & administração , Espanha/epidemiologiaRESUMO
Patient care after major head and neck surgery has changed in recent years. Tumors are the most common reasons for this type of surgery, though it is also used to treat benign conditions. Recent advances in equipment and surgical techniques have improved the postoperative course in this field, allowing early recovery, less pain and infection, a shorter hospital stay, and even better aesthetic results. This is due to the use of minimally invasive techniques, which are gaining relevance. Such techniques allow complex procedures in the head and neck region, through natural orifices or small incisions, with minimal damage and sequelae for the patients. Despite these advances, however, the complexity of the treatment intervention requires multidisciplinary patient management, mostly in the Intensive Care Unit, in order to monitor the possible occurrence of complications. Potential risk factors include previous comorbidity, the type of surgery involved (e.g., bilateral cervical lymphadenectomy), multiple transfusions, and the appearance of early complications requiring repeat surgery. Despite the existence of several studies, there are no standardized protocols for the postoperative period in surgeries of this kind. This causes many specialists to resort to accelerated recovery protocols (ERAS: "Enhanced Recovery After Surgery") that have already been established in other surgical specialties.
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Cuidados Críticos/métodos , Unidades de Terapia Intensiva , Procedimentos Cirúrgicos Bucais , Procedimentos Cirúrgicos Otorrinolaringológicos , Cuidados Pós-Operatórios/métodos , Manuseio das Vias Aéreas/métodos , Analgesia , Circulação Sanguínea , Humanos , Hipnóticos e Sedativos/uso terapêutico , Tempo de Internação , Insuficiência de Múltiplos Órgãos/terapia , Dor Pós-Operatória/terapia , Admissão do Paciente , Complicações Pós-Operatórias/terapia , Hemorragia Pós-Operatória/terapia , Procedimentos Cirúrgicos Robóticos , Transplante de Pele , Trombose/terapia , Fatores de TempoRESUMO
OBJECTIVE: First to identify the areas of improvement in the surgical area before and during the performance of a surgical procedure in general surgery through the application of a Modal Analysis of Failures and Effects. Second to establish preventive measures to avoid adverse events in the surgical area. METHOD: A multidisciplinary working group was created in a university hospital for risk management in the General Surgery Operating Room Unit. The Modal Analysis of Faults and Effects was used. Potential risks for the patient in the ante-surgery and within the operating room were identified. The Risk Priority Index was calculated and preventive measures were established for all of them, with special interest when the Risk Priority Index was higher than 100. Preventive measures were developed based on the detected risks as well as those responsible for them. RESULTS: We identified a greater number of risks when the patient is in the operating room than in the ante-surgery room. Those with a higher risk priority index were: anticoagulated or antiaggregated patients, urinary tract infections, osteoarticular or neuropathic problems, patients not prepared for colon surgery, errors in laterality and leaving compresses in the operative field. CONCLUSIONS: A risk map has been developed in our organization, allowing the design of strategies to improve Patient Safety in the Surgical area. Training is a key aspect to improve Patient Safety.
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Análise do Modo e do Efeito de Falhas na Assistência à Saúde/métodos , Salas Cirúrgicas , Gestão de Riscos/métodos , Gestão da Segurança/métodos , Procedimentos Cirúrgicos Operatórios , Anticoagulantes/administração & dosagem , Corpos Estranhos , Cirurgia Geral , Hospitais Universitários , Humanos , Cuidados Intraoperatórios , Erros Médicos/prevenção & controle , Assistência Perioperatória , Inibidores da Agregação Plaquetária/administração & dosagem , Cuidados Pré-Operatórios , Melhoria de Qualidade , Infecções Urinárias/complicaçõesRESUMO
OBJECTIVE: To assess the effectiveness of a proactive and integrated care programme to adjust the use of health resources by chronic complex patients (CCP) identified as potential high consumers according to a predictive model based on prior use and morbidity. METHODS: Randomized controlled clinical trial with three parallel groups of CCP: a blinded control group (GC), usual care; a partial intervention group (GIP) reported in the EMR; a total intervention group (GIT), also reported to primary care (PC). Conducted in an integrated health care organization (IHCO), N=128,281 individuals in 2011. Dependent variables: PC visits, emergency attention, hospitalizations, pharmaceutical cost and death. INDEPENDENT VARIABLES: intervention group, age, sex, area of residence, morbidity (by clinical risk group) and recurrence as CCP. STATISTICAL ANALYSIS: ANOVA, student's t test; logistic and multiple linear regressions at the 95% confidence level. RESULTS: 4,236 CCP included for the first intervention year and 4,223 for the second; recurrence as CCP 72%. Mean age 73.2 years, 54.2% women and over 70% with 2 or more chronic diseases. The number of PC visits was significantly higher for GIT than for GIP and GC. The hospital stays were significantly lower in GIP. This effect was observed in the first year and in the second year only in the new CCP. The general indicators of the IHCO were good, before and during the intervention. CONCLUSIONS: A high standard of quality, previous and during the study, and the inevitable contamination between groups, hindered the assessment of the marginal effectiveness of the program.
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Doença Crônica/terapia , Prestação Integrada de Cuidados de Saúde , Recursos em Saúde/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Custos de Medicamentos/estatística & dados numéricos , Emergências/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Modelos Organizacionais , Morbidade , Mortalidade , Visita a Consultório Médico/estatística & dados numéricos , Atenção Primária à Saúde/organização & administração , Avaliação de Programas e Projetos de Saúde , Recidiva , EspanhaRESUMO
BACKGROUND: Most acute coronary syndromes are caused by the fracture of a vulnerable atherosclerotic plaque. These plaques are thin cap fibroatheromas, which can only be detected with invasive coronary imaging techniques. It is necessary to find a non-invasive biomarker of these vulnerable plaques in order to identify patients at risk without a coronary angiography. Metalloproteinase-1 is an enzyme involved in extracellular matrix metabolism which has been correlated with the rupture of atherosclerotic plaques. Its serum levels in patients with vulnerable plaques remain unknown. METHODS: Patients with suspected stable coronary artery disease undergoing coronary angiography in our hospital were in-cluded. The coronary arteries were studied with optical coherence tomography to detect vulnerable plaques. Blood samples were taken from a peripheral vein and from the coronary sinus, to assess metalloproteinase-1 levels. RESULTS: Fifty-one patients were included, 13 of whom had at least one vulnerable plaque. There were not significant dif-ferences in clinical characteristics, lipid profile or C reactive protein levels, between patients with or without vulnerable plaques. Patients with vulnerable plaques had significant higher metalloproteinase-1 levels both in peripheral (7330±5541 vs 2894±1783 pg/ml, p=0.025) and coronary sinus serum (6012±3854 vs 2707±1252 pg/ml, p=0.047). CONCLUSIONS: Patients with vulnerable plaques had significantly higher metalloproteinase-1 serum levels. Further studies with clinical follow up are needed to assess the prognostic value of serum metalloproteinase-1.
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Doença da Artéria Coronariana/sangue , Metaloproteinase 1 da Matriz/sangue , Placa Aterosclerótica/sangue , Idoso , Estudos de Casos e Controles , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Estudos Prospectivos , Tomografia de Coerência ÓpticaAssuntos
Implantes Absorvíveis , Angina Instável/cirurgia , Estenose Coronária/cirurgia , Vasos Coronários/lesões , Intervenção Coronária Percutânea/efeitos adversos , Alicerces Teciduais , Idoso , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Humanos , Masculino , Ultrassonografia de IntervençãoRESUMO
BACKGROUND: Prognostic impact of anaemia in the elderly with acute coronary syndromes has not been specifically analysed, and little information exists about causes of mortality in this setting. METHODS: We prospectively included consecutive patients with acute coronary syndromes. Anaemia was defined as haemoglobin < 130 g/L in men, and < 120 g/L in women. Primary outcome was mid-term mortality and its causes. Analyses were performed by Cox regression method. RESULTS: We included 2128 patients, of whom 394 (18.6%) were aged 75 years or older. Anaemia was more common in the elderly (40.4% vs 19.5%, p <0.001). Mean follow-up was 386 days. Anaemia independently predicted overall mortality (HR 1.47, 95% CI 1.05-2.06), cardiac mortality (HR 1.76, 95% CI 1.06-2.94) and non-cardiac mortality (HR 1.59, 95% CI 1.03-2.45) in the overall cohort. In young patients the association between anaemia and mortality was significant only for non-cardiac causes. The association between anaemia and mortality was not significant in the elderly (HR 1.08, 95% CI 0.71-1.63, p 0.736). CONCLUSIONS: The impact of anaemia on cause specific of mortality seem to be different according to age subgroup. The association between anaemia and mortality was not observed in elderly patients from our series.
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Síndrome Coronariana Aguda/epidemiologia , Anemia/epidemiologia , Causas de Morte , Idoso Fragilizado , Sistema de Registros , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anemia/diagnóstico , Anemia/terapia , Comorbidade , Estudos Transversais , Feminino , Avaliação Geriátrica , Humanos , Incidência , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Espanha , Análise de Sobrevida , Centros de Atenção TerciáriaRESUMO
AIMS: To compare the degree of endothelial dysfunction (ED) in patients treated with everolimus-eluting stent (EES) versus bare metal stent (BMS) implantation. METHODS AND RESULTS: This is an observational study. A total of 30 elective patients (15 treated with EES and 15 with BMS) were recruited. All patients underwent coronary angiography and intracoronary acetylcholine (Ach) test at different doses at six months after stent implantation. Quantitative coronary angiography analysis was performed to evaluate the changes in mean luminal diameter (MLD) of the segments distal to the distal stent edge after increasing doses of Ach. Both EES and BMS groups had similar baseline characteristics except for stent length (18.6±2.5 vs. 16.5±2.5 mm; p=0.033) and diameter (3.1±0.2 vs. 3.4±0.3 mm; p=0.007). The vasomotion test showed that EES had 3.14% of MLD decrease after Ach infusion and BMS had 2.35% of vasoconstriction (p=0.62). After adjustment for baseline characteristics, no statistical difference was observed between groups. CONCLUSIONS: In our study EES implantation was associated with a low degree of ED and had a similar vasomotion response as compared to BMS. Prospective randomised investigations are warranted to confirm these findings.