After reviewing Multifactor Dimensionality Reduction(MDR) and its extensions, an approach to obtain P(larger than 1) risk scores is proposed to predict the continuous outcome for each subject. We study the mean square error(MSE) of dimensionality reduced models fitted with sets of 2 risk scores and investigate the MSE for several special cases of the covariance matrix. A methodology is proposed to select a best set of P risk scores when P is specified a priori. Simulation studies based on true models of different dimensions(larger than 3) demonstrate that the selected set of P(larger than 1) risk scores outperforms the single aggregated risk score generated in AQMDR and illustrate that our methodology can determine a best set of P risk scores effectively. With different assumptions on the dimension of the true model, we considered the preferable set of risk scores from the best set of two risk scores and the best set of three risk scores. Further, we present a methodology to access a set of P risk scores when P is not given a priori. The expressions of asymptotic estimated mean square error of prediction(MSPE) are derived for a 1-dimensional model and 2-dimensional model. In the last main chapter, we apply the methodology of selecting a best set of risk scores where P has been specified a priori to Alzheimer’s Disease data and achieve a set of 2 risk scores and a set of three risk scores for each subject to predict measurements on biomarkers that are crucially involved in Alzheimer’s Disease.

Introducción: Las recomendaciones del ATPIII y las SSCC europeas en prevención primaria cardiovascular aconsejan para la estimación del riesgo individual las funciones de Framingham y SCORE respectivamente. Ambas disponen de versiones calibradas para la población española. Todas, excepto Framingham(ATPIII), han sido derivadas para aplicarlas en un rango de edad limitado. Por otra parte, ninguna de estas funciones predice el riesgo cardiovascular total, ya que SCORE y SCORE calibrada sólo estima el riesgo de muerte y Framingham(ATPIII) y REGICOR el riesgo coronario. Sin embargo todas las medidas preventivas van dirigidas a la prevención de la enfermedad cardiovascular globalmente y las funciones son utilizadas como proxi del riesgo cardiovascular total. El objetivo es determinar cuál de estas funciones de estimación del riesgo cardiovascular es más útil para seleccionar al mayor número de pacientes con incidencia total de episodios cardiovasculares elevada. Método: Estudio observacional de cohortes de 1642 pacientes de 20 a 79 años no diabéticos, sin enfermedad cardiovascular establecida, en una Unidad de Hipertensión y Riesgo Vascular, seguidos un tiempo mediano de 3,8 años (rango 1- 10 años). Se registraron todos los episodios cardiovasculares mayores incidentes. Se calculó el riesgo predicho individual utilizando cada función. Se analizó el grado de concordancia para clasificar en grupos de riesgo utilizando los puntos de corte ≥5% en SCORE y SCORE calibrada, >20% para Framingham(ATPIII) y ≥10% en REGICOR. Se estimó para cada función la sensibilidad, especificidad, CPP, CPN, Odds ratio diagnóstica y exactitud. Se estimó la densidad de incidencia por el método de Mantel-Haenzel, y la incidencia acumulada en grupos de riesgo obtenidos al aplicar los algoritmos y compararlos mediante análisis de Kaplan-Meier. Se compararon las curvas de supervivencia mediante test de Breslow. Resultados: SCORE calibrada clasificó de alto riesgo a un 13,5%, SCORE a un 9,8%, Framingham(ATPIII) al 8,8% y REGICOR a un 3,5%. Durante el seguimiento 74 pacientes presentaron un primer episodio cardiovascular. La concordancia a la hora de clasificar en grupos de riesgo entre Framingham y SCORE (Kappa=0,37), y entre SCORE calibrada y REGICOR (Kappa=0,34) fue débil. Para cada función, el grupo de alto riesgo presentó un HR superior a 4 respecto al grupo de riesgo moderado/bajo. Todas las funciones presentaron una baja sensibilidad sin diferencias significativas, así como una exactitud moderada para discriminar pacientes con episodio cardiovascular. Al comparar SCORE vs Framingham(ATPIII) y SCORE calibrada vs REGICOR, la incidencia de episodios cardiovasculares en los grupos con discordancia en la clasificación de alto riesgo no presentó diferencias significativas. SCORE excluyó un 4,8% de pacientes de alto riesgo frente a un 5,8% por Framingham(ATPIII). SCORE calibrada excluyó un 0,4% de pacientes de alto riesgo frente a un 10,3% en el caso de REGICOR. Además, SCORE calibrada seleccionó un 4,2% más de pacientes respecto a SCORE con una incidencia significativamente más elevada que el grupo de riesgo moderado/bajo. En las mujeres por falta de potencia estadística no se observaron diferencias significativas. En los hombres SCORE excluyó un 7,1% de pacientes de alto riesgo frente a un 10,6% por Framingham(ATPIII), mientras que SCORE calibrada excluyó un 0,4% de pacientes de alto riesgo frente a un 16,1% por REGICOR con una probabilidad acumulada de ECV a los 5 años del 19%. Además, SCORE calibrada incluyó un 5% más de pacientes que SCORE con una probabilidad acumulada de episodios cardiovasculares a los 5 años del 17%. Conclusión: En prevención primaria, aunque el rendimiento de las cuatro funciones analizadas no presenta diferencias significativas, la concordancia entre ellas es débil, siendo SCORE calibrada la más útil para seleccionar al mayor número de pacientes con una incidencia de episodios cardiovasculares aumentada. / Background: The recommendations of ATPIII and the European scientific societies in cardiovascular primary prevention advise the estimate of the individual risk by Framingham and SCORE functions respectively. Both have versions calibrated for the Spanish population. The objective is to determine which of these functions is more useful to select to the greater number of patients with high cardiovascular incidence. Method: Longitudinal study of 1642 non-diabetic patients, without previous history of cardiovascular disease attending to a Hypertension and Vascular clinic. High-risk patients were considered those with ≥5% risk according to SCORE and calibrated SCORE, >20% on Framingham(ATPIII) and ≥10% on REGICOR. Major cardiovascular events were collected during a 3 year median follow-up (range 1-10 años) and analysed by Kaplan-Meier. Results: 13,5% of patients was considered of high-risk with calibrated SCORE function, 9,8& with SCORE, 8,8% with Framingham(ATPIII) and 3,5% with REGICOR. The concordance between SCORE and Framingahm(ATPIII) (Kappa=0,37), and between calibrated SCORE and REGICOR (Kappa=0,34) was poor. During follow-up 74 cardiovascular events occurred. The incidence of cardiovascular events in groups with disagreement in high risk classification, did not present differences, upon compared SCORE vs Framingham(ATPIII) and calibrated SCORE vs REGICOR. SCORE excluded a 4,8% of high risk patients as compared to a 5,8% by Framingham(ATPIII). Calibrated SCORE excluded a 0,4% of high risk patients as compared to a 10,3% in the case of REGICOR. Furthermore, calibrated SCORE selected 4,2% patients more than SCORE with incidence of cardiovascular events significantly highest that moderate/low risk group. In women, by lack of statistics power, it’s not observed meaningful differences. In the men SCORE excluded 7,1% of high risk patients as compared to 10,6% by Framingham(ATPIII). Calibrated SCORE excluded 0,4% of high risk patients as compared to 16,1% by REGICOR with acumulative probability of cardiovascular events at 5 years of 19%. Furthermore, calibrated SCORE included a 5% of men more than SCORE with an acumulative probability of cardiovascular events at 5 years of 17%. Conclusions: In primary prevention, calibrated SCORE is the most useful to select the greater number of patients with a cardiovascular events incidence increased.

Since January 2006 Medicare beneficiaries have the option to purchase prescription drug benefits from Medicare under the Part D program. The addition of outpatient drugs to the Medicare programs reflects Congress’ recognition of the fundamental change in recent years in how medical care is delivered in the U.S. It recognizes the vital role of prescription drugs in the health care delivery system and the need to modernize Medicare to assure their availability to Medicare beneficiaries. The Medicare Prescription Drug Improvement and Modernization Act of 2003 (MMA) created the Medicare drug benefit and specified a standard plan. The law also enables plans to offer alternative benefit packages that are either actuarially equivalent or provide enhanced benefits above the basic benefits. A majority of these alternative plans offer multitiered formulary where different medications have different patient copayments. Different from traditional Medicare, Part D benefits are provided by private sector plans through a competitive bidding process. Firms submit a bid to the Center for Medicare and Medicaid Services (CMS) which represents the expected cost to the firm for providing basic benefits to an individual of average health. The competition between plans was expected to drive premiums down toward marginal cost, ensuring that the beneficiaries receive maximum benefits for a given public expenditure (Biles et al. 2004). This dissertation examines the stand-alone Medicare Prescription Drug Plans (PDPs) bid and premium from the following perspectives using the 2006-2008 PDP data. First, we examine the use of multiple-tier copayment structures. In particular, we tend to discover the relationship between enrollee cost sharing at each tier and prescription drug plan (PDP) bids. Bids are equivalent to the total premiums charged by an insurer. This includes the premium paid by the consumer and the portion paid by the federal government. Further, we decompose plan bid and premium changes between 2006 and 2008 into two components, the proportion due to changes in plan characteristics and the proportion due to changes in marginal price. By doing so, we estimate whether the actuarial methods used to price those characteristics play a role in explaining the plan bid and premium difference across years.  Finally, we measure the Medicare beneficiaries’ sensitivity to price in the PDP market, specifically the elasticity and semi-elasticity of enrollment with respect to PDP premium.

Submitted by MARINA LUCCHINI PONTES NOGUEIRA (malpnogueira@hotmail.com) on 2018-10-15T14:42:37Z No. of bitstreams: 1 Dissertação de Mestrado. Marina Lucchini Pontes Nogueira.pdf: 2279326 bytes, checksum: d24b92bfe972adff14b64721bb4cfb22 (MD5) / Approved for entry into archive by ROSANGELA APARECIDA LOBO null (rosangelalobo@btu.unesp.br) on 2018-10-16T12:58:11Z (GMT) No. of bitstreams: 1 nogueira_mlp_me_bot.pdf: 2279326 bytes, checksum: d24b92bfe972adff14b64721bb4cfb22 (MD5) / Made available in DSpace on 2018-10-16T12:58:11Z (GMT). No. of bitstreams: 1 nogueira_mlp_me_bot.pdf: 2279326 bytes, checksum: d24b92bfe972adff14b64721bb4cfb22 (MD5) Previous issue date: 2018-09-19 / Introdução: O transporte inter-hospitalar de recém-nascidos (RN) para centros terciários muitas vezes é inevitável e está associado a maior o risco para morbidades e para o óbito. A hipótese deste estudo é de que os transportes realizados na região estejam ocorrendo de forma inadequada, piorando o prognóstico dos RN transportados. Objetivos: Determinar o perfil dos RN transportados, avaliar a adequação dos transportes e calcular os escores de risco TRIPS e Ca-TRIPS, correlacionando-os com o risco de óbito e hemorragia peri-intraventricular (HPIV), na primeira semana pós-transporte. Metodologia: Estudo prospectivo de corte transversal, realizado de junho 2014 a dezembro de 2017, incluindo todos os RN submetidos a transporte e internados na Unidade Neonatal do Hospital das Clínicas da Faculdade de Medicina de Botucatu, sem exclusão. As variáveis avaliadas foram: peso ao nascer (PN), idade gestacional (IG), sexo, tipo de parto, apgar, necessidade de reanimação em sala de parto, indicação da transferência, utilização de incubadora apropriada, presença de acesso venoso, drogas e fluidos utilizados, suporte respiratório, tempo de vida à internação, temperatura axilar, padrão respiratório, pressão arterial, uso de drogas vasoativas, estado neurológico e valores dos escores de risco à internação. Os pacientes foram acompanhados na primeira semana pós-transporte em relação à evolução para HPIV ou óbito. Resultados apresentados em tabelas de frequência, com cálculo das médias e desvio padrão ou medianas e percentis; calculados os valores de sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo para os escores. Teste do qui-quadrado foi utilizado no estudo das associações e realizado cálculo do risco relativo para análise dos desfechos (α=0,05). Resultados: Foram estudados 271 RN, a maioria nascidos a termo (medianas de peso: 2975g e IG: 38 semanas). Quase 30% dos pacientes foram transportados da própria cidade de Botucatu, porém 7,7% percorreram distâncias maiores que 150km. O transporte foi inadequado em 86% dos casos: sem incubadora de transporte: 26%; sem acesso venoso: 38%; sem infusão de fluidos: 40%; distermia: 53%; hipo ou hiperglicemia: 33%; hipoxemia: 20%; hipotensão: 19%; bradicardia: 3%. Os valores do TRIPS variaram de 0-65 (mediana: 6) e Ca-TRIPS de 0-60 (mediana: 20) e 31% dos RN apresentaram TRIPS ≥ 10. Valores de TRIPS ≥ 10 foram observados em 27% dos recém-nascidos a termo (RNT) vs 40% dos prematuros (PT) (P=0,04). TRIPS ≥ 10 aumentou o risco de HPIV entre os PT (R.R. = 4,04 - IC95%: 1,23-13,29 – P = 0,023) e o risco de morte entre todos os RN (R.R. = 7,45 - IC95%: 2,87-19,52 - P < 0,001). RN com Ca-TRIPS ≥ 20,5, apresentaram maior risco de morte (R.R. = 13,3 - IC95%: 4,05-43,81 - P < 0,001). Ambos os escores apresentaram valores preditivos positivos e negativos semelhantes. Conclusão: O transporte foi inadequado na maioria dos casos. Embora apenas 30% dos RN tenham sido PT, estes apresentaram valores mais altos de TRIPS e Ca-TRIPS, em comparação aos RNT. Pacientes com escores de risco mais elevados apresentaram maior riscos de óbito e HPIV. / Introduction: Interhospital transport of newborns (NB) to tertiary centers is often unavoidable and associated with greater risk for morbidity and death. The hypothesis of this study is that transport in the region is occurring inadequately, worsening the prognosis of the transported NB. Objectives: To determine the profile of the transported NB, to assess the adequacy of the transports and to calculate the TRIPS and Ca-TRIPS risk scores, correlating them with the risk of death and peri-intraventricular hemorrhage (PIVH) in the first week after transport. Methods: Prospective cross-sectional study, carried out from June 2014 to December 2017, including all NB submitted to transportation and hospitalized at the Neonatal Unit of the Hospital das Clínicas da Faculdade de Medicina de Botucatu, without exclusion. The variables evaluated were: birth weight, gestational age, sex, type of delivery, apgar, need for resuscitation in the delivery room, indication of transference, use of appropriate incubator, presence of venous access, drugs and blood flow used, respiratory support, age at admission, axillary temperature, breathing pattern, blood pressure, use of vasoactive drugs, neurological status, and values of risk scores at the time of admission. Patients were followed in the first post-transport week in relation to the progression to PIVH or death. Results presented in frequency tables, with calculation of means and standard deviation or medians and percentiles; values of sensitivity, specificity, positive predictive value and negative predictive value were calculated for the scores. Chi-square test was used in the study of associations and relative risk (RR) was calculated for the analysis of the outcomes (α=0.05). Results: We studied 271 newborns most born at term (medians weight: 2975g and gestacional age: 38 weeks). Almost 30% of the patients were transported from the city of Botucatu, but 7,7% traveled more than 150km. Transport was inadequate in 86% of cases: without transport incubator: 26%; without venous access: 38%; without fluid infusion: 40%; dysthermia: 53%; hypo or hyperglycemia: 33%; hypoxemia: 20%; hypotension: 19%; bradycardia: 3%. The TRIPS values ranged from 0-65 (median: 6) and Ca-TRIPS from 0-60 (median: 20) and 31% from the NB presented TRIPS ≥10. TRIPS values ≥ 10 were observed in 27% of the full-term newborn vs. 40% of preterm (P = 0.04). TRIPS ≥ 10 increased the risk of PIVH among premature infants (RR = 4.04 - 95% CI: 1.23-13.29 - P = 0.023) and the risk of death among all NB (RR=7,45 – IC95%: 2.87-19.52 - P <0.001). NB with Ca-TRIPS ≥ 20.5 presented higher risk of death (RR=13.3 - 95% CI: 4.05-43.81 - P <0.001). Both scores had similar positive and negative predictive values. Conclusion: Transportation was inadequate in most cases. Although only 30% of the newborns were preterm infants, they presented higher values of TRIPS and Ca-TRIPS compared to the full-term newborns. Patients with higher risk scores had a higher risk of death and PIVH.

Coronary artery disease (CAD) is associated with significant morbidity and mortality. Coronary artery calcification (CAC) indicates presence of CAD. Absence of CAC is associated with very low risk of having CAD but not equal to zero. In this study, we aim at developing a clinical prediction tool to predict presence of obstructive CAD among patients with zero calcium score. We developed two models. A full prespecified model with 7 variables based on input from clinical experts, and a reduced model with 4 variables based on univariate screening. Both models showed an acceptable performance (c-statistics of 0.68 for both). Both models performed well when validated, externally for the full model and internally for the reduced one. We derived a clinical risk score of 20 points from the full model. We found that a score threshold of ≥ 14 is associated with presence of obstructive CAD with positive likelihood ratio of 5.5.

Orientador: João Cesar Lyra / Resumo: Introdução: O transporte inter-hospitalar de recém-nascidos (RN) para centros terciários muitas vezes é inevitável e está associado a maior o risco para morbidades e para o óbito. A hipótese deste estudo é de que os transportes realizados na região estejam ocorrendo de forma inadequada, piorando o prognóstico dos RN transportados. Objetivos: Determinar o perfil dos RN transportados, avaliar a adequação dos transportes e calcular os escores de risco TRIPS e Ca-TRIPS, correlacionando-os com o risco de óbito e hemorragia peri-intraventricular (HPIV), na primeira semana pós-transporte. Metodologia: Estudo prospectivo de corte transversal, realizado de junho 2014 a dezembro de 2017, incluindo todos os RN submetidos a transporte e internados na Unidade Neonatal do Hospital das Clínicas da Faculdade de Medicina de Botucatu, sem exclusão. As variáveis avaliadas foram: peso ao nascer (PN), idade gestacional (IG), sexo, tipo de parto, apgar, necessidade de reanimação em sala de parto, indicação da transferência, utilização de incubadora apropriada, presença de acesso venoso, drogas e fluidos utilizados, suporte respiratório, tempo de vida à internação, temperatura axilar, padrão respiratório, pressão arterial, uso de drogas vasoativas, estado neurológico e valores dos escores de risco à internação. Os pacientes foram acompanhados na primeira semana pós-transporte em relação à evolução para HPIV ou óbito. Resultados apresentados em tabelas de frequência, com cálculo das médias e desvio ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Interhospital transport of newborns (NB) to tertiary centers is often unavoidable and associated with greater risk for morbidity and death. The hypothesis of this study is that transport in the region is occurring inadequately, worsening the prognosis of the transported NB. Objectives: To determine the profile of the transported NB, to assess the adequacy of the transports and to calculate the TRIPS and Ca-TRIPS risk scores, correlating them with the risk of death and peri-intraventricular hemorrhage (PIVH) in the first week after transport. Methods: Prospective cross-sectional study, carried out from June 2014 to December 2017, including all NB submitted to transportation and hospitalized at the Neonatal Unit of the Hospital das Clínicas da Faculdade de Medicina de Botucatu, without exclusion. The variables evaluated were: birth weight, gestational age, sex, type of delivery, apgar, need for resuscitation in the delivery room, indication of transference, use of appropriate incubator, presence of venous access, drugs and blood flow used, respiratory support, age at admission, axillary temperature, breathing pattern, blood pressure, use of vasoactive drugs, neurological status, and values of risk scores at the time of admission. Patients were followed in the first post-transport week in relation to the progression to PIVH or death. Results presented in frequency tables, with calculation of means and standard deviation or medians and percentiles; values of sensiti... (Complete abstract click electronic access below) / Mestre

INTRODUÇÃO: O Transplante de Células-tronco Hematopoéticas (TCTH) alogênico é uma modalidade de tratamento com capacidade de curar várias doenças hematológicas benignas e malignas. Os progressos nesta área aumentaram o número e melhoraram os desfechos dos procedimentos realizados, porém sua morbimortalidade permanece elevada. Em 2009, o escore de risco do EBMT foi validado como um método simples para predizer, com dados pré-transplante, os desfechos de um paciente após o TCTH alogênico. OBJETIVOS: O objetivo deste estudo foi validar a aplicabilidade do escore de risco do EBMT em pacientes brasileiros do Hospital de Cínicas de Porto Alegre (HCPA), submetidos a TCTH alogênico. MÉTODOS: Foi realizado um estudo retrospectivo, observacional, com dados coletados de prontuários de 278 pacientes (156 homens (56%) com mediana de idade de 32 anos) submetidos ao TCTH alogênico no HCPA para doenças malignas e anemia aplástica severa, entre 1994 e 2010. Foi aplicado o escore de risco do EBMT e analisados os desfechos sobrevida global (OS), mortalidade não relacionada à recaída (NRM) e taxa de recaída (RR). RESULTADOS: OS, NRM e RR em cinco anos foram de 53,4%, 39% e 30,7%, respectivamente. A OS em pacientes com risco 0 foi significativamente maior (81,8%) do que os de risco 6 (20%) (p<0,001). Da mesma forma, pacientes com risco 0 tiveram menor NRM (13,6%) do que os com risco 6 (80%) (p=0,001). O estágio avançado da doença foi associado com aumento de RR em todas as patologias neoplásicas avaliadas. CONCLUSÃO: O escore de risco do EBMT pode ser utilizado como um dado adicional na avaliação de pacientes com doenças malignas e anemia aplástica severa com indicação de TCTH alogênico no nosso centro. / BACKGROUND: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is a treatment modality able to cure many hematological disorders. Although utilized with increasing frequency and success, it is still associated with a high transplant related mortality rate. In 2009, the EBMT risk score was validated as a simple tool to predict outcome after allogeneic HSCT for acquired hematological disorders. OBJECTIVES: The aim of this study was to validate the applicability of the EBMT risk score for allogeneic HSCT on south Brazilian patients, from a single center. METHODS: A retrospective observational study was performed based on patients’ records and data base of Hematology and Bone Marrow Transplantation Department at Hospital de Clínicas de Porto Alegre, including all allogeneic transplants for malignant and severe aplastic anemia from 1994 to 2010. Patients were categorized according to EBMT risk score and overall survival (OS), non-relapse mortality (NRM) and relapse rate (RR) were analyzed. RESULTS: There were 278 evaluable patients, of whom 56% were male, and the median age was 32 years. OS, NRM, and RR at five years median follow up, were 53,4%, 39%, and 30,7%, respectively. The OS was 81,8% for risk score 0 and 20% for score 6 (p<0,001), and NRM 13,6% and 80% for risk score 0 and 6, respectively (p=0,001). Advanced disease stage was associated with an increased RR in all evaluated neoplastic disorders. CONCLUSION: The EBMT risk score can be utilized as a tool for clinical decision-making before allogeneic HSTC for malignant hematological diseases and severe aplastic anemia at a single center, in Brazil.

INTRODUÇÃO: O Transplante de Células-tronco Hematopoéticas (TCTH) alogênico é uma modalidade de tratamento com capacidade de curar várias doenças hematológicas benignas e malignas. Os progressos nesta área aumentaram o número e melhoraram os desfechos dos procedimentos realizados, porém sua morbimortalidade permanece elevada. Em 2009, o escore de risco do EBMT foi validado como um método simples para predizer, com dados pré-transplante, os desfechos de um paciente após o TCTH alogênico. OBJETIVOS: O objetivo deste estudo foi validar a aplicabilidade do escore de risco do EBMT em pacientes brasileiros do Hospital de Cínicas de Porto Alegre (HCPA), submetidos a TCTH alogênico. MÉTODOS: Foi realizado um estudo retrospectivo, observacional, com dados coletados de prontuários de 278 pacientes (156 homens (56%) com mediana de idade de 32 anos) submetidos ao TCTH alogênico no HCPA para doenças malignas e anemia aplástica severa, entre 1994 e 2010. Foi aplicado o escore de risco do EBMT e analisados os desfechos sobrevida global (OS), mortalidade não relacionada à recaída (NRM) e taxa de recaída (RR). RESULTADOS: OS, NRM e RR em cinco anos foram de 53,4%, 39% e 30,7%, respectivamente. A OS em pacientes com risco 0 foi significativamente maior (81,8%) do que os de risco 6 (20%) (p<0,001). Da mesma forma, pacientes com risco 0 tiveram menor NRM (13,6%) do que os com risco 6 (80%) (p=0,001). O estágio avançado da doença foi associado com aumento de RR em todas as patologias neoplásicas avaliadas. CONCLUSÃO: O escore de risco do EBMT pode ser utilizado como um dado adicional na avaliação de pacientes com doenças malignas e anemia aplástica severa com indicação de TCTH alogênico no nosso centro. / BACKGROUND: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is a treatment modality able to cure many hematological disorders. Although utilized with increasing frequency and success, it is still associated with a high transplant related mortality rate. In 2009, the EBMT risk score was validated as a simple tool to predict outcome after allogeneic HSCT for acquired hematological disorders. OBJECTIVES: The aim of this study was to validate the applicability of the EBMT risk score for allogeneic HSCT on south Brazilian patients, from a single center. METHODS: A retrospective observational study was performed based on patients’ records and data base of Hematology and Bone Marrow Transplantation Department at Hospital de Clínicas de Porto Alegre, including all allogeneic transplants for malignant and severe aplastic anemia from 1994 to 2010. Patients were categorized according to EBMT risk score and overall survival (OS), non-relapse mortality (NRM) and relapse rate (RR) were analyzed. RESULTS: There were 278 evaluable patients, of whom 56% were male, and the median age was 32 years. OS, NRM, and RR at five years median follow up, were 53,4%, 39%, and 30,7%, respectively. The OS was 81,8% for risk score 0 and 20% for score 6 (p<0,001), and NRM 13,6% and 80% for risk score 0 and 6, respectively (p=0,001). Advanced disease stage was associated with an increased RR in all evaluated neoplastic disorders. CONCLUSION: The EBMT risk score can be utilized as a tool for clinical decision-making before allogeneic HSTC for malignant hematological diseases and severe aplastic anemia at a single center, in Brazil.

INTRODUÇÃO: O Transplante de Células-tronco Hematopoéticas (TCTH) alogênico é uma modalidade de tratamento com capacidade de curar várias doenças hematológicas benignas e malignas. Os progressos nesta área aumentaram o número e melhoraram os desfechos dos procedimentos realizados, porém sua morbimortalidade permanece elevada. Em 2009, o escore de risco do EBMT foi validado como um método simples para predizer, com dados pré-transplante, os desfechos de um paciente após o TCTH alogênico. OBJETIVOS: O objetivo deste estudo foi validar a aplicabilidade do escore de risco do EBMT em pacientes brasileiros do Hospital de Cínicas de Porto Alegre (HCPA), submetidos a TCTH alogênico. MÉTODOS: Foi realizado um estudo retrospectivo, observacional, com dados coletados de prontuários de 278 pacientes (156 homens (56%) com mediana de idade de 32 anos) submetidos ao TCTH alogênico no HCPA para doenças malignas e anemia aplástica severa, entre 1994 e 2010. Foi aplicado o escore de risco do EBMT e analisados os desfechos sobrevida global (OS), mortalidade não relacionada à recaída (NRM) e taxa de recaída (RR). RESULTADOS: OS, NRM e RR em cinco anos foram de 53,4%, 39% e 30,7%, respectivamente. A OS em pacientes com risco 0 foi significativamente maior (81,8%) do que os de risco 6 (20%) (p<0,001). Da mesma forma, pacientes com risco 0 tiveram menor NRM (13,6%) do que os com risco 6 (80%) (p=0,001). O estágio avançado da doença foi associado com aumento de RR em todas as patologias neoplásicas avaliadas. CONCLUSÃO: O escore de risco do EBMT pode ser utilizado como um dado adicional na avaliação de pacientes com doenças malignas e anemia aplástica severa com indicação de TCTH alogênico no nosso centro. / BACKGROUND: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is a treatment modality able to cure many hematological disorders. Although utilized with increasing frequency and success, it is still associated with a high transplant related mortality rate. In 2009, the EBMT risk score was validated as a simple tool to predict outcome after allogeneic HSCT for acquired hematological disorders. OBJECTIVES: The aim of this study was to validate the applicability of the EBMT risk score for allogeneic HSCT on south Brazilian patients, from a single center. METHODS: A retrospective observational study was performed based on patients’ records and data base of Hematology and Bone Marrow Transplantation Department at Hospital de Clínicas de Porto Alegre, including all allogeneic transplants for malignant and severe aplastic anemia from 1994 to 2010. Patients were categorized according to EBMT risk score and overall survival (OS), non-relapse mortality (NRM) and relapse rate (RR) were analyzed. RESULTS: There were 278 evaluable patients, of whom 56% were male, and the median age was 32 years. OS, NRM, and RR at five years median follow up, were 53,4%, 39%, and 30,7%, respectively. The OS was 81,8% for risk score 0 and 20% for score 6 (p<0,001), and NRM 13,6% and 80% for risk score 0 and 6, respectively (p=0,001). Advanced disease stage was associated with an increased RR in all evaluated neoplastic disorders. CONCLUSION: The EBMT risk score can be utilized as a tool for clinical decision-making before allogeneic HSTC for malignant hematological diseases and severe aplastic anemia at a single center, in Brazil.

The use of cardiovascular risk scores remains the foundation for risk stratification to guide clinical management. Clinicians have access to several cardiovascular risk scores in practice settings. While having several risk scores with different risk factors may provide more information, it does not imply accuracy of the cardiovascular risk score used to calculate individual patient cardiovascular risk. The objective of this study was to compare the Framingham Risk score, Reynolds Risk scores, and the Pooled Cohort Risk Equation (3 commonly used equations) scores with respect to ability to predict cardiovascular events in a diverse ethnic population. Additionally, the potential predictive utility of three novel risk factors (carotid intima media thickness, peripheral arterial tonometry and vasa vasorum) was examined in relation to ability to improve 10-year cardiovascular risk prediction. A secondary analysis of the longitudinal prospective study cohort known as Heart Strategies Concentrating On Risk Evaluation (Heart SCORE) was conducted. The cardiovascular risk scores of study participants who did and did not experience a cardiovascular event composite index consisting of myocardial infarction, death, stroke, acute ischemic stroke, or revascularization were assessed using methods of calibration and discrimination overall and by race and gender. When examining performance of the 3 risk scores, the overall 10-year absolute predicted cardiovascular risk varied substantially (e.g. approximately 2-fold) and this wide variation in predicted 10-year cardiovascular risk was present across race and gender. Nonetheless, despite the wide variation in estimates of absolute risk, the 3 cardiovascular risk score equations were strongly associated with future cardiovascular risk overall and by race and gender. There was some indication that the Reynolds risk score was the most accurate measure of future cardiovascular risk. The 3 novel risk factors examined did not significantly improve 10-year cardiovascular risk prediction above and beyond the standard demographic and clinical variables used in these well-known equations.