O objetivo deste estudo foi analisar os perfis de diagnósticos de enfermagem e dos domínios da classificação antes e após a implementação da classificação da North American Nursing Diagnosis Association – International (NANDA-I) na Clínica Médica do Hospital Universitário da Universidade de São Paulo (HU-USP), realizada entre os anos de 2001 e 2004. A amostra foi composta pelos registros de enfermagem de 31 pacientes admitidos em agosto de 2001 (fase pré, sexo masculino=61,3%, idade média=53,6±20,9 anos, internação por doenças do aparelho circulatório=30%) e de 30 admitidos em agosto de 2004 (fase pós, sexo feminino=60,0%, idade média=60,9±23,1 anos, doenças do aparelho respiratório=30%). Todos os registros de enfermagem das primeiras 24 horas de internação foram manualmente transcritos. Na fase pré foi utilizada a técnica de mapeamento cruzado para inferir os diagnósticos segundo a taxonomia da NANDA-I. Os diagnósticos da fase pós foram transcritos dos registros. Os critérios para incluir os diagnósticos das duas fases para as análises finais foram: consenso de painel de três juízes e a existência de pelo menos um item de prescrição de enfermagem pertinente. As associações entre as freqüências de diagnósticos, domínios e as fases do estudo foram testadas, com nível de significância ?0,10. Os perfis de diagnósticos e domínios foram descritos pela Análise Fatorial Múltipla (AFM). Na fase pré, os diagnósticos mais freqüentes foram: integridade da pele prejudicada (54,8%), dor aguda (48,4%) e risco para integridade da pele prejudicada (45,2%), e na fase pós: dor aguda (66,7%), integridade tissular prejudicada (32,3%) e desobstrução ineficaz de vias aéreas para (43,3%). Seis diagnósticos apresentaram diferença estatística entre as duas fases: integridade da pele prejudicada (de 54,8% para 33,3%, p=0,092); nutrição desequilibrada: menos que as necessidades corporais (de 25,8% para ausência de ocorrência, p=0,005); deambulação prejudicada (de 19,4% para nenhuma ocorrência, p=0,024); proteção ineficaz (de nenhuma ocorrência para 23,3%, p=0,005); perfusão tissular renal (de nenhuma ocorrência para 16,7%, p=0,024); ansiedade (de nenhuma ocorrência para 13,3%, p=0,053). Foram identificados seis domínios na fase pré e sete na pós. Houve diferenças significativas nos domínios: conforto (de 48,3% para 73,3%, p=0,046); nutrição (de 25,8% para 6,6%, p=0,023) e enfrentamento/tolerância ao estresse (de nenhuma ocorrência para 13,3%, p=0,053). Essas diferenças indicam que, após a implementação da classificação, houve maior focalização de respostas de conforto e de enfrentamento e tolerância ao estresse. A AFM indicou diferentes perfis de diagnósticos e de domínios entre as fases, mostrando que na fase pós houve maior amplitude dos fenômenos focalizados pelas enfermeiras. A implementação da classificação da NANDA-I contribuiu para ampliar o foco do cuidado, aumentando a ênfase em fenômenos pouco documentados, como os do domínio de enfrentamento e tolerância ao estresse. O fato de as enfermeiras documentarem esses fenômenos como diagnósticos aumenta a responsabilidade na seleção de intervenções adequadas e na avaliação dos resultados obtidos. Os resultados deste estudo são contribuições importantes para aprimorar os processos de implementação das classificações e para monitorar os seus efeitos na prática clínica de enfermagem. / The aim of this study was to analyze the profiles of nursing diagnoses and domains of the classification before and after the implementation of NANDA-I (North American Nursing Diagnosis Association – International) in the Medical Clinic of the Hospital Universitário da Universidade de São Paulo (HU-USP), carried out from 2001 to 2004. The sample was composed by the nursing records from 31 patients admitted in August 2001 (pre-implementation phase, male=61.3%, mean age=53.6±20.9 years old, admittance due to circulatory system diseases=30%) and from 30 patients admitted in August 2004 (phase post, female=60.0%, mean age=60.9±23.1 years old, respiratory system diseases=30%). All nursing records from the first 24 hours of admittance were manually transcribed. In the phase pre the cross-mapping technique was applied in order to infer the diagnoses according to the NANDA-I taxonomy. The phase post diagnoses were transcribed from the records. The analysis criteria to include the diagnoses from both stages were: a three-referee panel consensus and the existence of at least one pertinent nursing order item. The associations among the diagnose frequencies, domains and study phases were tested, with a significance level of ?0.10. The profiles of diagnoses and domains were described by the Multiple Factorial Analysis (MFA). In the phase pre, the most frequent diagnoses were: skin integrity impaired (54.8%), acute pain (48.4%) and skin integrity impaired risk (45.2%), and in the phase post: acute pain (66.7%), tissue integrity impaired (32.3%) and airway clearence innefective (43.3%). Six diagnoses had statistic difference between the two phases: skin integrity impaired (from 54.8% to 33.3%, p = 0.092); unbalanced nutrition: less than the body requirement (from 25.8% to non-occurrence, p = 0.005); impaired walking (from 19.4% to non-occurrence, p = 0.024); ineffective protection (from non-occurrence to 23.3%, p = 0.005); tissue perfusion ineffective renal (from non-occurrence to 16.7%, p = 0.024); anxiety (from non-occurrence to 13.3%, p = 0.053). Six domains in the phase pre, and seven in the phase post were identified. There were significant differences in the following domains: comfort (from 48.3% to 73.3%, p = 0.046); nutrition (from 25.8% to 6.6%, p = 0.023) and coping/stress tolerance (from non-occurrence to 13.3%, p = 0.053). These differences indicate that, after the implementation classification, there were greater focus on comfort responses and coping/stress tolerance. The MFA presented different profiles of diagnoses and domains between the phases, indicating that on the phase post there was greater amplitude of the phenomena focused by the nurses. The NANDA-I classification implementation contributes to widen the care focus, increasing the emphasis on less-documented phenomena, as the ones of the coping/stress tolerance domain. The fact that the nurses documented such phenomena as diagnoses increases the responsibility in the selection of proper interventions and in the evaluation of the outcomes. The results to this study are important contributions, which aim at improving the processes of the classification implementation, and at monitoring their effects on the nursing clinical practice.

Submitted by Cristiane Chim (cristiane.chim@ucpel.edu.br) on 2018-04-12T11:58:06Z No. of bitstreams: 1 GUSTAVO GONZALES REAL.pdf: 452117 bytes, checksum: a8fec397aed279b25dead9e47bbe6937 (MD5) / Made available in DSpace on 2018-04-12T11:58:06Z (GMT). No. of bitstreams: 1 GUSTAVO GONZALES REAL.pdf: 452117 bytes, checksum: a8fec397aed279b25dead9e47bbe6937 (MD5) Previous issue date: 2017-08-29 / Introduction: Hospital readmissions are common and potentially preventable, being considered marker of poor quality of a health service. The literature shows readmission rates around 20% and identified some risk factors such as length of stay, polypharmacy and more comorbidity. There is increasing interest in identifying potentially reversible risk factors, including the patient nutritional status. Several studies have shown a strong association between malnutrition and a prolonged hospitalization, increased mortality, increased hospital costs and high rates of hospital readmission. However, these studies did not evaluate only clinical patients and are difficult to extrapolate to the Brazilian reality in which the hospitalized patients have different clinical characteristics, socioeconomic and nutritional status. Objective: This study aimed to identify risk factors for hospital readmissions in medical patients admitted to a university hospital in southern Brazil. Method: This is a prospective cohort study assessing predictors of hospital readmission in patients who stays more than 24 hours in Internal Medicine ward during the period January to June 2016. The data relating to social and demographic profile, the presence of comorbidities, use of medicines and nutritional assessment will be collected within 24 hours of admission of the patient and every 7 days we will repeat the assessment of nutritional status (subjective global assessment produced by the patient, bioelectrical impedance analysis, grip strength and calf circumference). In the seven and thirty days after discharge, the patient will receive a phone call to verify the occurrence of and readmission or need for consultation in the health service. Expected results: it is expected that a lower socioeconomic status, patients with more comorbidity, longer hospital stays, polypharmacy and worse nutritional status exhibit higher readmission rates. Keywords: hospital readmissions, assessment of nutritional status, risk factors, internal medicine / Introdução: As readmissões hospitalares são eventos comuns e potencialmente evitáveis, sendo consideradas marcadoras de má qualidade de um serviço de saúde. A literatura evidencia taxas de readmissão em torno de 20% e identifica alguns fatores de risco como tempo de internação, polifarmácia e maior número de comorbidades. Atualmente, é crescente o interesse na identificação de fatores de risco potencialmente reversíveis, dentre eles o estado nutricional do paciente. Diversos estudos têm evidenciado uma forte associação entre a desnutrição e uma internação prolongada, aumento de mortalidade, aumento dos custos hospitalares e altas taxas de readmissão hospitalar. Entretanto, tais estudos não avaliaram exclusivamente pacientes clínicos e são de difícil extrapolação para a realidade brasileira, na qual a população de pacientes hospitalizados possui características clinicas, socioeconômicas e nutricionais diferentes. Objetivo: Esse estudo teve como propósito identificar fatores de risco para readmissão hospitalar em pacientes clínicos internados em um hospital universitário do sul do Brasil. Método: trata-se de uma coorte prospectiva que avaliará fatores preditores de readmissão hospitalar em pacientes com internação maior que 24 horas na enfermaria de Clínica Médica durante o período de janeiro a junho de 2016. Os dados referentes ao perfil social e demográfico, presença de comorbidades, medicamentos em uso e avaliação nutricional serão coletados nas primeiras 24 horas da internação do paciente e a cada 7 dias será repetida a avaliação do estado nutricional (avaliação subjetiva global produzida pelo paciente, bioimpedância elétrica, dinamometria e circunferência da panturrilha). No sétimo e no trigésimo dias após a alta, o paciente receberá uma ligação telefônica para verificar a ocorrência de readmissão e ou necessidade de consulta em serviço de saúde. Resultados esperados: espera-se que uma pior condição socioeconômica, pacientes com muitas comorbidade, com maior tempo de internação, com polifarmácia e com pior condição nutricional apresentem taxas de readmissão maiores.

El objetivo de este estudio fue evaluar si la escala CURB-65, índice de mortalidad validado en neumonía comunitaria, podía aplicarse también en pacientes hospitalizados en Medicina Interna, donde no se han desarrollado escalas pronósticas. Para ello estudiamos prospectivamente una cohorte de 539 pacientes (51% varones; media de edad: 78 años; mortalidad: 12%) ingresados en el Hospital Sierrallana (Cantabria). Se recogieron diversos datos clínicos, epidemiológicos y analíticos. La puntuación en la escala CURB-65 fue significativamente más alta en los pacientes fallecidos (86% vs 30%; p<0,001), asociándose la puntuación alta con una mortalidad más elevada (RR 38,16 (5,16-281,5). La sensibilidad y especificidad de la puntuación alta fueron 85% y 69% respectivamente, y el valor predictivo negativo del 100%. También se calculó la curva ROC (área bajo la curva: 0,79). Nuestros resultados sugieren que la escala CURB-65 puede ser útil para predecir la mortalidad en pacientes hospitalizados en Medicina Interna. / The aim of this study was to evaluate if CURB-65 score, validated as mortality index in Community Acquired Pneumonia, could also be used in patients admitted to an Internal Medicine Service, where prognostic scores have not been developed. We analyzed prospectively a cohort of 539 patients (51% males; mean age: 78; mortality: 12%) admitted to Hospital Sierrallana (Cantabria). Clinical and epidemiological data and laboratory findings were examined. CURB-65 score was significantly higher in patients who died (86% vs 30%; p<0,001), and high CURB-65 score was associated with higher mortality (RR 38,16 (5,16-281,5)). Sensitivity and specificity for high CURB-65 score were 85% and 69%, respectively, and negative predictive value was 10%. Curve ROC was also calculated (area under the curve: 0,79). Our findings suggested that CURB-65 score can be an useful tool for predicting mortality in patients admitted to an Internal Medicine Service.

Deficiency of antithrombin caused by mutations affecting the gene encoding this key anticoagulant (SERPINC1) significantly increases the risk of thrombosis. We aim to identify new mechanisms involved in antithrombin deficiency. Using molecular, cellular and biochemical methods, we studied 29 patients with antithrombin deficiency without SERPINC1 mutation, a family study, three case-control studies including 2,980 patients and 3,996 controls, and two patients with congenital disorder of glycosylation (CDG). We identified the first mutation affecting the SERPINC1 promoter causing antithrombin deficiency. We confirmed the low genetic variability of SERPINC1 and its minor role on the heritability of antithrombin. Genome wide association studies and silencing experiments identified the first modulating gene of antithrombin, LARGE. We diagnosed a patient with CDG based on his antithrombin deficiency. Finally, we described a new disorder with identical biochemical features than CDGs, but only thrombosis, which is caused by a single mutation in PMM2 and concomitant alcohol consumption. / La deficiencia de antitrombina causada por mutaciones en el gen SERPINC1 incrementa el riesgo trombótico. Nuestro objetivo fue identificar nuevos mecanismos implicados en la deficiencia de este anticoagulante. Empleando metodología molecular, celular y bioquímica estudiamos 29 pacientes con deficiencia de antitrombina sin mutaciones en SERPINC1, un estudio familiar, tres estudios caso-control (2,980 pacientes/3,996 controles) y dos pacientes con trastornos congénitos de glicosilación (CDG). Identificamos la primera mutación en el promotor de SERPINC1 que causa deficiencia de antitrombina. Confirmamos la baja variabilidad genética en SERPINC1 y su escasa influencia en la heredabilidad de antitrombina. Un GWAS y experimentos de silenciamiento mostraron que LARGE es el primer gen modulador de antitrombina. Diagnosticamos un CDG por la deficiencia de antitrombina de un paciente con trombosis recurrente y descubrimos nuevo desorden con patrón bioquímico similar al CDG pero solo con trombosis que es causado por una sola mutación en PMM2 y consumo de alcohol.

Objetivos: Determinar si los pacientes octogenarios reciben con la misma frecuencia que los pacientes más jóvenes los tratamientos médicos y de reperfusión recomendados tras un infarto agudo de miocardio (IAM) durante su ingreso en las Unidades Coronarias.Métodos: Estudio observacional, longitudinal y prospectivo de los pacientes ingresados consecutivamente durante 10 años en dos Unidades Coronarias con un IAM. Se comparó la administración de los tratamientos médicos y la realización de los tratamientos de reperfusión recomendados en las guías de práctica clínica en los pacientes octogenarios frente al resto de pacientes más jóvenes mediante el análisis de regresión multivariante ajustado por los antecedentes personales, género y situación clínica al ingreso. Además, se comprobó la posible existencia de un efecto lineal de la edad en la administración de dichos tratamientos. Conclusiones: Los pacientes octogenarios con un IAM reciben con menos frecuencia los fármacos recomendados en las guías de práctica clínica que han demostrado una mejoría del pronóstico. Asimismo, a los octogenarios con infarto agudo de miocardio sin elevación del segmento ST se les realiza con menos frecuencia un intervencionismo coronario. En cambio, reciben con la misma frecuencia que los pacientes más jóvenes los tratamientos de reperfusión de fibrinólisis o intervencionismo coronario percutáneo primario.Aims: To determine whether patients aged 80 and over diagnosed with acute myocardial infarction (AMI) and admitted to coronary care units receive recommended medical and reperfusion treatments with the same frequency as younger patients.Methods: A longitudinal, observational, prospective cohort study of patients diagnosed with an AMI and consecutively admitted to two coronary care units over the course of 10 years. We analyzed the frequency with which guideline-recommended medical and reperfusion treatments were administered to patients aged 80 and over in comparison to how often such treatments were given to younger patients using a multivariate regression adjusted for personal medical history, gender, and clinical status at the time of admission. We also examined the possibility of a linear effect for age in the administration of guideline-recommended treatments.Conclusion: AMI patients aged 80 and over are less likely than younger patients to be given guideline-recommended drugs with proven prognostic benefits. Likewise, non-ST-segment elevation acute myocardial infarction patients aged 80 and over receive fewer coronary interventions than their younger counterparts. However, patients aged 80 and over receive reperfusion, fibrinolytic and primary percutaneous coronary intervention treatments at the same rate as younger patients.

A pesar de la importancia de las Agudizaciones en la Enfermedad Pulmonar Obstructiva Crónica(AEPOC), sabemos poco de sus determinantes. OBJETIVOS Analizar la existencia de un ‘Fenotipo Agudizador’(FA) y estimar la existencia de predictores de AEPOC. Evaluar la capacidad predictiva de un índice de gravedad propio(IGP). METODOLOGÍA Estudio de cohortes retrospectivo. Identificándose 900 pacientes con EPOC en Cantabria a 31/12/2011, en bases de datos poblacionales. Se clasificó a cada paciente como ‘FA’, o como ‘Fenotipo No Agudizador’(FNA), en 2012. La frecuencia de agudizaciones graves y la mortalidad global fueron también tratadas como variables dependientes. RESULTADO-CONCLUSIONES El principal predictor independiente de ser ‘FA’ fue el antecedente de agudizaciones el año previo, apoyando la existencia de un ‘FA’ estable. El IGP obtuvo una buena capacidad predictiva de ser ‘FA’, hospitalización por AEPOC y mortalidad al año. El añadir las comorbilidades, aumentó esta capacidad. La vacunación antigripal, disminuyó el riesgo de hospitalización por AEPOC. / Despite the importance of exacerbations of chronic obstructive pulmonary disease(COPD), we know relatively little about their determinants. OBJECTIVES To analyze whether there is or not a ‘Frequent-Exacerbation’(FE) phenotype of COPD and to discover exacerbation predictors.To estimate the predictive accuracy of an own index of severity. METHODS Retrospective population-based cohort study. 900 patients with confirmed COPD ≥ 35 years, were selected in Cantabria at 31 December 2011. We defined ‘FE’ and ‘Infrequent Exacerbator’(IE) phenotype in 2012. Frequency of severe exacerbations, and overall mortality were also treated as dependent variables. RESULTS-CONCLUSIONS The main predictor of ‘FE’ was a history of frequent exacerbations the previous year, and it supports a ‘FE’ phenotype of COPD. Our composite score obtained a high predictive accuracy of being ‘FE’, COPD hospitalization and overall mortality next year. Adding comorbidities increased this predictive accuracy. Influenza vaccination diminished the risk of hospitalization by exacerbation the following year.

Tesis por compendio de publicaciones / Se planteo una línea de investigación sobre la utilidad de nuevos biomarcadores y una nueva técnica, la tomografía de coherencia óptica, en el diagnostico del rechazo agudo y la enfermedad vascular del injerto, en pacientes trasplantados cardiacos. Concluimos: 1. Los episodios de rechazo asocian un incremento en los niveles de péptido natriurético B, troponina T de alta sensibilidad y de sST2. Esto puede ser útil en el diagnostico no invasivo del rechazo, ayudando a reducir el número de biopsias y sus costes. 2. Las concentraciones de troponina T de alta sensibilidad se correlacionan con la severidad de la enfermedad vascular del injerto y puede ser útil en la detección de enfermedad vascular severa. 3. La tomografía de coherencia óptica en la evaluación de la enfermedad vascular del injerto muestra una buena correlación con la ecografía intravascular, con la ventaja de una menor variabilidad y mejor caracterización de la placa. / We propose an investigation to assess the possible utility of new emerging biomarkers and a new imaging technique, the Optical Coherence Tomography, in the early diagnostic of graft dysfunction due to acute cellular rejection or cardiac allograph vasculopathy in heart transplant patients After this investigation we conclude: 1. Acute rejection episodes were associated with marked increments in B-Type Natriuretic Peptide, Highly sensitive troponin T and sST2 levels. This could be useful in the noninvasive diagnosis of acute rejection, helping to reduce the number of programmed endomyocardial biopsies and related costs. 2. Highly sensitive troponin T concentrations correlates with the severity of cardiac allograph vasculopathy and could be useful in the early detection of severe cardiac allograph vasculopathy. 3. Optical coherence tomography in the evaluation of cardiac allograph vasculopathy showed a good correlation with intravascular ultrasound measurements, taking advantage of lower interobserver variability and better plaque characterization.

Tesis por compendio de Publicaciones / La presencia de lesiones coronarias severamente calcificadas es un hallazgo frecuente que dificulta la dilatación mediante balón, pudiendo causar infraexpansión del stent, por lo que se han asociado a una mayor tasa de complicaciones y un peor resultado a largo plazo. Para luchar contra estas limitaciones se desarrolló la aterectomía rotacional (AR), que permite mediante la ablación diferencial, reduciendo las complicaciones y mejorando la tasa de éxito en el implante de stent. En este trabajo se sitúa la AR en el actual contexto del intervencionismo coronario y se estudia su adaptación a nuevas técnicas, indicaciones y escenario farmacológico. El desarrollo de los stent liberadores de fármaco (SLF) redujo la tasa de restenosis respecto a los stents convencionales. Sin embargo, en los estudios no se incluyó a pacientes previamente tratados mediante AR. En nuestro trabajo, tras un estudio retrospectivo sobre una serie consecutiva de 50 pacientes demostramos la efectividad del implante de stent liberador de paclitaxel tras la AR con una supervivencia libre de muerte cardiaca del 94% y una supervivencia libre de revascularización de la lesión tratada de un 94% tras 1 año de seguimiento. La mejora en los resultados de los SLF extendió la aplicación de la AR a escenarios complejos. En este trabajo se presentan los datos de la primera serie de 40 pacientes consecutivos con enfermedad de tronco común tratado mediante AR. La supervivencia libre de mortalidad cardíaca fue del 71 ± 7% a los dos años del procedimiento. La tasas de revascularización del vaso tratado a los 2 años fue del 19,3 ± 7%, mostrando ser un procedimiento de alto riesgo, opción terapeútica para pacientes no operables. Paralelamente, pequeños estudios previos a la generalización de clopidogrel previo al intervencionismo coronario, demostraron que la administración de abciximab reducía la hypoperfusion transitoria asociada al procedimiento de aterectomía rotacional. Sin embargo, no hay estudios que lo hayan demostrado en pacientes bajo doble tratamiento antiagregante (DAPT). En este trabajo se evaluó la reducción del daño miocárdico periprocedimiento (DMRP) proporcionado por abciximab en pacientes bajo DAPT en una serie consecutiva de 139 pacientes, de los cuales 48 habían recibido abciximab. La incidencia de DMRP en pacientes que recibieron abciximab y aquellos que no fue de 22,9% vs 20,9% (p= 0.664). En un subanalisis restringido a pacientes diabéticos , la incidencia de DMRP fue del 27,5% en los que recibieron abciximab frente a un 18,6% en los que no (p= 0.435). Tras construir un modelo de regresión, solo la longitud de stent implantada resultó ser un predictor de DMRP (OR 1,026, CI 1,006- 1,047; p< 0.011). La administración de abciximab no mostró reducir el daño miocárdico relacionado con el procedimiento en pacientes tratados mediante aterectomía rotacional e implante de stent. / Calcified atherosclerotic lesions are present between 50% en 80% of coronary angiograms, increasing its prevalence with age. Heavily calcified coronary lesions hinder balloon dilatation causing stent underexpansion, being associated with higher complication rate ad worse long-term outcomes. To deal with this limitation, rotational atherectomy (RA) allows plaque remodeling and facilitates stent implantation with a higher success and lower complication rates. In this paper we explore the role of RA in an novel scenario of new stents, extended indications and renewed ancillary therapy. Paclitaxel-eluting stents (PESs) have been shown to help reduce restenosis and rotational atherectomy facilitates angioplasty and stent implantation in heavily calcified lesions. However, the major studies of PESs have considered this an exclusion criterion. The present study analyzes immediate and 1-year results following treatment of heavily calcified lesions with RA and PES implantation, showing a 94% survival free of cardiac death and 94% TLR-free survival at 1 year, proving an excellent result for this strategy. This study also carried out an evaluation of the immediate and long term results of a consecutive series of patients with severely calcified lesions in unprotected left main rejected for surgical treatment and treated using PCI with RA in a single center. Forty patients were included. Cardiac mortality-free survival rate was 71 ± 7% two years after the procedure; target vessel revascularization rates at 2 years were 19.3 ± 7%. At the time of last contact, 60 % of treated patients were angina-free. Although RA on severely calcified unprotected left main is a high risk procedure, according to our results, it is a treatment option for patients who are not suitable for surgery who would otherwise not receive any interventional treatment. The third part of this essay was conducted to evaluate whether abciximab is associated with a reduction in procedure-related myocardial injury, in a consecutive series of patients pretreated with clopidogrel who underwent RA and stent implantation in severely calcified lesions. Procedural success was achieved in 127 (91.4%) patients with no significant difference between naive and abciximab treated patients (90% vs 94%; p= 0.537). The incidence of procedure-related myocardial injury in patients who received abciximab and patients who did not was 22.9% vs 20.9% (p= 0.664). A subanalysis restricted to diabetic patients was also performed. The incidence of procedure-related myocardial injury in diabetics was 27.5% in those who received abciximab vs. 18.6 % in those who did not received the drug (p= 0.435). In a logistic regression analysis, only the stent length was predictor of peri-procedural MI (OR 1.026, CI 1.006- 1.047; p< 0.011). After adjusting for clinical and procedural parameters, the use of abciximab did not show to reduce periprocedural myocardial damage. The administration of abciximab was not associated with a benefit in terms of procedure-related myocardial injury reduction.

Tesis por compendio de publicaciones / A lo largo de esta Tesis Doctoral hemos comprobado la influencia que tienen los polimorfismos rs9923231 de VKORC1, rs1799853 y rs1057910 de CYP2C9 y rs2108622 de CYP4F2 en el control del tratamiento con Acenocumarol al inicio de la terapia. El primer objetivo (búsqueda de nuevas variantes génicas que influyeran en la dosis estable de la terapia oral anticoagulante, de cara a incluirlas en un futuro algoritmo), concluimos que dada la baja frecuencia de las nuevas variantes encontradas y de la pequeña mejora que supone su incorporación al algoritmo de predicción de dosis (1%), no encontramos argumentos que justifiquen su inclusión en dichos métodos predictivos. Al abordar el segundo objetivo valoramos cuáles eran los principales factores clínicos y genéticos que tenían mayor relevancia para un control óptimo de la terapia oral al inicio del tratamiento. Con estos datos posteriormente elaboramos un algoritmo de predicción de dosis estable, en lo que sería el tercer objetivo. METODOS: Se realizó un estudio retrospectivo de cohortes en la anticoagulación Unidad de Terapia, Hospital Morales Meseguer (Murcia, España). El estudio fue aprobado por las juntas de ética de la investigación en la institución. Los pacientes que reciben tratamiento anticoagulante con acenocumarol terapia se hacen pruebas de elegibilidad en la base de datos de nuestra anticoagulación Unidad de terapia. En primer lugar, se seleccionaron aquellos pacientes que tenían tratamiento iniciado con acenocumarol en nuestra clínica ambulatoria constituyendo la cohorte primaria. En segundo lugar, hemos validado el algoritmo en una segunda población (cohorte de validación) de los pacientes que están siendo controlados en nuestra Unidad. Algunos pacientes con valores perdidos por lo menos uno de los determinantes o los que no alcanzan un fase estable dentro de un año después del inicio de la terapia. RESULTADOS: En cuanto al primer objetivo concluimos que dada la baja frecuencia de las nuevas variantes encontradas y de la pequeña mejora que supone su incorporación al algoritmo de predicción de dosis (1%), no encontramos argumentos que justifiquen su inclusión en dichos métodos predictivos. En cuanto al segundo objetivo, los resultados de este trabajo muestran que el INR a las 72 horas del inicio de la terapia es un potente predictor de los principales objetivos de la misma, sobre-anticoagulación y dosis estable a los tres meses del inicio. Adicionalmente, además del efecto bien conocido de los polimorfismos de VKORC1 y CYP2C9, el polimorfismo rs2108622 de CYP4F2 tiene un efecto significativo en la sobre-dosificación de Acenocumaro durante los primeros tres meses de tratamiento. En cuanto al tercer objetivo, con nuestros datos, el mejor modelo de predicción de dosis incluye factores clínicos (edad y superficie corporal) y genéticos (polimorfismos de VKORC1, CYP2C9 y CYP4F2) y explica hasta el 50% de la variación de la dosis. Este algoritmo resulta especialmente útil para pacientes que necesitan dosis extremas de Acenocumarol (≤7mg/semana y ≥25mg/semana), ya que proporciona una estimación en un rango de ±20% de la dosis real. Dado que estos pacientes son los que normalmente necesitan más tiempo para su estabilización y son los que con más frecuencia sufren efectos adversos derivados del tratamiento, puede ser relevante emplear este algoritmo en la práctica clínica en nuestra población Y finalmente, aunque fuera del cuerpo principal de esta Tesis, realizamos un estudio aleatorizado donde comprobamos la eficacia y seguridad de nuestro algoritmo de predicción de dosis comparado con el sistema habitual de dosificación en dos grupos de pacientes. De los resultados de este trabajo se concluye que la inclusión del valor del INR a las 72 horas en el sistema de dosificación que tiene en cuenta la información genética es crucial para que este esquema sea superior al método clásico en los objetivos analizados (porcentaje de pacientes con dosis estable, porcentaje de INRs en rango y tiempos para alcanzar ambos objetivos). Sin embargo, a los 6 meses de inicio del tratamiento, la valoración de estos objetivos se iguala en ambas ramas, de donde podemos concluir que la información genética es especialmente relevante al inicio de la terapia (3 primeros meses). Tras este periodo, otros factores inherentes a los pacientes van modulando la dosis necesaria para estar en INR terapéutico. / Throughout this thesis we have tested the influence of the VKORC1 rs9923231 , rs1799853 and rs1057910 and rs2108622 CYP2C9 polymorphisms of CYP4F2 in the control treatment Acenocumarol the beginning of therapy. The first objective ( finding new gene variants that influenced the stable dose of oral anticoagulant therapy , in order to include them in a future algorithm) , we conclude that given the low frequency of new variants found and small improvement achieved its Join the dose prediction algorithm (  1%) , we find arguments that justify their inclusion in such predictive methods . In addressing the second objective value which were the main clinical and genetic factors were most important for optimal control of oral therapy at baseline . With these data subsequently developed a prediction algorithm stable dose , in what would be the third objective . METHODS : A retrospective cohort study was performed on Anticoagulation Therapy Unit , Hospital Morales Meseguer (Murcia , Spain ) . The study was approved by the boards of research ethics in the institution. Patients receiving anticoagulant therapy with acenocoumarol eligibility tests are done in the database of our anticoagulation therapy unit . First, those patients who had started treatment with acenocoumarol in our outpatient clinic constituting the primary cohort were selected. Second, we validated the algorithm in a second population ( validation cohort ) of patients being monitored in our unit. Some patients with missing at least one of the key or the failure to achieve a stable phase within one year after the initiation of therapy values . RESULTS : Regarding the first objective we conclude that given the low frequency of new variants found and small improvement achieved by incorporating the prediction algorithm dose (  1%) , we find arguments that justify their inclusion in such predictive methods . Regarding the second objective , the results of this work show that the INR at 72 hours after initiation of therapy is a powerful predictor of the main objectives of the same , over- anticoagulation and stable at three months of starting dose . Additionally , besides the well known effect of CYP2C9 and VKORC1 polymorphisms , of CYP4F2 rs2108622 polymorphism has a significant effect on the over- dosing of Acenocumaro during the first three months of treatment . As for the third goal, with our data, the best prediction model includes clinical dose (age and body surface area) and genetic factors (polymorphisms of VKORC1 , CYP2C9 and CYP4F2 ) and explains up to 50 % of the variation in dose. This algorithm is especially useful for patients who need extreme Acenocumarol dose ( ≤ and ≥ 7mg/semana 25mg/semana ) , providing an estimate within a range of ± 20% of the actual dose . Since these patients are normally need more time to stabilize and are the most frequently suffer adverse effects from treatment , may be relevant to use this algorithm in clinical practice in our population And finally , even if the main body of this thesis , we conducted a randomized study in which the efficacy and safety check of our prediction algorithm compared with the usual dose dispensing system on two groups of patients. From the results of this study concluded that the inclusion of the value of the INR at 72 hours in the metering system that takes into account genetic information is crucial in this scheme is higher than the classical method in the objectives analyzed ( percentage of patients with stable dose , percentage of INRs in range and times for both targets ) . However, at 6 months of starting treatment , assessment of these objectives is equal in both directions, from which we can conclude that genetic information is particularly relevant to the initiation of therapy ( first 3 months) . After this period, other factors inherent to patients will be necessary to modulate the INR in therapeutic doses .

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