Antiarrhythmic active components in traditional Chinese medicine acting on potassium channels / 中国中药杂志

Arrhythmia is an external manifestation of cardiac electrophysiological disorder. It exists in healthy people and patients with various heart diseases, which is often associated with other cardiovascular diseases. The contraction and diastole of myocardium are inseparable from the movement of ions. There are many ion channels in the membrane and organelle membrane of myocardium. The dynamic balance of myocardial ions is vital in maintaining myocardial electrical homeostasis. Potassium ion channels that have a complex variety and a wide distribution are involved in the whole process of resting potential and action potential of cardiomyocytes. Potassium ion channels play a vital role in maintaining normal electrophysiological activity of myocardium and is one of the pathogenesis of arrhythmia. Traditional Chinese medicine(TCM)has unique advantages in treating arrhythmia for its complex active components and diverse targets. A large number of TCM preparations have definite effect on treating arrhythmia-related diseases, whose antiarrhythmic mechanism may be related to the effect on potassium channel. This article mainly reviewed the relevant studies on the active components in TCM acting on different potassium channels to provide references for clinical drug use and development.

Recomendaciones para el manejo de la cardiotoxicidad relacionada con el tratamiento del cáncer. Segunda parte / Recommendations for the management of cardiotoxicity related to cancer treatment. Part two / Recomendações para a gestão de cardiotoxicidade relacionada com o tratamento do câncer. Primeira [i.e. Segunda] parte

Las nuevas terapias oncológicas han logrado aumentar la sobrevida del paciente con cáncer, observando, sin embargo, un incremento de la morbilidad y mortalidad vinculadas a sus efectos secundarios. El desarrollo de eventos cardiovasculares adversos impacta negativamente en el pronóstico durante el tratamiento del cáncer, pero también en los supervivientes al cáncer, donde las enfermedades cardiovasculares (ECV) y las segundas neoplasias son la principal causa de muerte1-5. La cardiotoxicidad inducida por el tratamiento del cáncer se define como el conjunto de ECV derivadas de los tratamientos oncológicos. Su manifestación es variada e incluye el desarrollo de disfunción ventricular, insuficiencia cardíaca (IC), isquemia miocárdica, hipertensión arterial (HTA) y arritmias, entre otras. Puede ser consecuencia tanto del efecto directo del tratamiento sobre la estructura y función cardíacas, como del desarrollo acelerado de enfermedad cardiovascular6-9. Con frecuencia, se utiliza el término cardiotoxicidad como sinónimo de disfunción ventricular por quimioterapia (DV-QT). Dado que la cardiotoxicidad abarca un espectro más amplio de afectación cardiovascular, creemos conveniente hablar de DV-QT para referirnos a la afectación de la función sistólica del ventrículo izquierdo. La DV-QT y el desarrollo de IC representan una de las complicaciones más temidas por su impacto pronóstico en la esfera cardiovascular y oncológica, dado que limitan el arsenal terapéutico para el tratamiento del cáncer5,10. Han sido creadas diversas sociedades de cardio-onco-hematología con el fin de generar recomendaciones de práctica clínica y formar profesionales capacitados para el manejo de las complicaciones CV del tratamiento del cáncer11. La cardio-oncología es una disciplina en creciente y continuo desarrollo. Creemos que es fundamental realizar tareas de formación médica continua, así como también estimular el trabajo conjunto de diversas especialidades para brindar una mejor asistencia. Este texto es el resultado del trabajo de un equipo multidisciplinario que incluye cardiólogos, hematólogos y oncólogos, y pretende brindar información a los integrantes del equipo de salud involucrados en la asistencia de pacientes oncológicos. Debido a la extensión del presente texto, hemos decidido fraccionar el contenido en tres partes para facilitar su difusión.

New oncological therapies have been successful in increasing cancer patient survival, but they have also led to an increase in morbidity and mortality linked to their side effects. During cancer treatment, the development of cardiovascular side effects has a negative impact in prognosis, but also in cancer survivors, in whom cardiovascular diseases and secondary malignancies are the main cause of death. Cancer related cardiotoxicity is defined as the development of cardiovascular diseases related to cancer treatment. Clinical presentation is broad involving ventricular dysfunction, heart failure, myocardial ischemia, arterial hypertension and arrhythmias among others. This may result from the direct cardiovascular effect of a cancer treatment or accelerated development of cardiovascular diseases. Frequently, in the literature cardiotoxicity and chemotherapy related ventricular dysfunction are used as synonyms. However, cardiotoxicity includes a broad spectrum of cardiovascular manifestations, thus in this text we refer to chemotherapy related ventricular dysfunction as the presence of left ventricular systolic impairment. Chemotherapy related ventricular dysfunction and heart failure are two of the most feared complications of cancer treatment due to its impact on cardiovascular and oncological prognosis, affecting treatment options. Numerous worldwide cardio-onco-hematology societies have emerged to generate clinical practice guidelines and improve the diagnosis and evaluation of cardiovascular cancer treatment side effects. Cardio-Oncology is a discipline in continuous growth and development. We strongly believe that continuum medical education and a multidisciplinary approach is necessary to provide a quality health care. This text is the result of a multidisciplinary work involving cardiologists, hematologists and oncologists. It is our goal to provide information to the health care team involved in the assistance of cancer patients. Due to its extension, it will be divided in three parts.

O desenvolvimento de novas terapias oncológicas levou a um aumento na sobrevida dos pacientes, mas ao mesmo tempo traz consigo morbidades relacionadas aos tratamentos. O desenvolvimento de efeitos cardiovasculares adversos tem um impacto negativo no prognóstico dos pacientes em tratamento, bem como nos pacientes considerados curados, nos quais doença cardiovascular e malignidades secundárias são as principais causas de morte. Cardiotoxicidade relacionada ao câncer é definida como o desenvolvimento de doença cardiovascular secundária ao tratamento. A gama de apresentações clínicas é ampla, podendo se manifestar como disfunção ventricular, insuficiência cardíaca, isquemia miocárdica, hipertensão arterial, arritmias, entre outras. Isto pode ser resultante de desenvolvimento e progressão acelerados de doença cardiovascular ou por efeito direto das terapias. Frequentemente é dito na literatura que cardiotoxicidade e disfunção ventricular relacionada à quimioterapia são sinônimos. Entretanto, cardiotoxicidade engloba um amplo espectro de manifestações cardiovasculares. Neste texto, portanto, nos referimos à disfunção ventricular causada por quimioterápicos exclusivamente como a presença de disfunção sistólica ventricular esquerda. Disfunção ventricular relacionada à quimioterapia e insuficiência cardíaca são duas das mais temidas complicações do tratamento oncológico devido ao seu impacto no prognóstico cardiovascular e oncológico, podendo afetar ainda a escolha e manutenção das opções terapêuticas. Diversas sociedades cardio-onco-hematológicas surgiram ao redor do mundo com o objetivo de gerar diretriz clínicas práticas e melhorar o diagnóstico e tratamento das complicações cardiovasculares resultantes das terapias oncológicas. A cardio-oncologia é uma disciplina em contínuo crescimento e desenvolvimento. Nós acreditamos fortemente que educação médica continuada e uma abordagem multidisciplinar são necessárias para um cuidado médico de qualidade. Este texto é o resultado de um trabalho multidisciplinar envolvendo cardiologistas, hematologistas e oncologistas. Nosso objetivo é de oferecer informação à equipe de cuidados em saúde envolvido na assistência destes pacientes. Devido à sua extensão, este texto será dividido em três partes.

População com risco cardiovascular elevado em uso de medicamento e aconselhamento: a situação do Brasil em relação à meta mundial, 2014-2015 / Población de riesgo cardiovascular elevado en uso de medicamento y asesoramiento: la situación de Brasil en relación al objetivo mundial, 2014-2015 / Population with high cardiovascular risk receiving drug therapy and counseling: Brazil's status regarding the global goal, 2014-2015

Objetivo: Estimar a prevalência de risco cardiovascular (RCV) elevado, a proporção de pessoas com RCV elevado que recebem tratamento e aconselhamento, e investigar os fatores sociodemográficos associados ao desfecho, no Brasil. Métodos: Estudo transversal, com dados de subamostra da Pesquisa Nacional de Saúde, coletados por exames bioquímicos, em 2014-2015. Empregou-se regressão de Poisson. Resultados: A proporção de RCV elevado em homens foi de 11,2% (IC95% 9,6;12,9), e em mulheres, de 10,4% (IC95% 9,2;11,8%). No grupo com RCV elevado, 68,8% (IC95% 63,7;73,4%) receberam aconselhamento; 59,3% (IC95% 54,2;64,3%), medicamento; e 55,6% (IC95% 50,4;60,7%), ambos. Na análise multivariável, receber tratamento e aconselhamento mostrou associação com a idade de 50 anos e mais, e com autoavaliação de saúde ruim/muito ruim (RP=1,26 - IC95% 1,06;1,51). Conclusão: A proporção de pessoas com RCV elevado que receberam tratamento e aconselhamento foi superior a 50%.

Objetivo: Estimar la prevalência de riesgo cardiovascular (RCV) elevado, la proporción de personas con RCV elevado que reciben tratamiento y asesoramiento, e investigar los factores sociodemográficos asociados al resultado, en Brasil. Métodos: Estudio transversal, con datos de la submuestra de la Investigación Nacional de Salud, recolectados por exámenes bioquímicos, en 2014-2015. Se usó la regresión de Poisson. Resultados: La proporción de RCV elevado en hombres fue del 11,2% (IC95% 9,6; 12,9) y en mujeres del 10,4% (IC95% 9,2;11,8%). En el grupo con RCV elevado, 68,8% (IC95% 63,7; 73,4%) recibió asesoramiento, 59,3% (IC95% 54,2;64,3%) medicamento y 55,6% (IC95% 50,4;60,7%) ambos. En el análisis multivariable, recebir tratamiento y asesoramiento se mostró asociado a la edad de 50 años y más, y a autoevaluación de salud mala/muy mala (RP=1,26 - IC95% 1,06;1,51). Conclusión: La proporción de personas con RCV elevado que recibió tratamiento y asesoramiento fue superior a 50%.

Objective: To estimate the prevalence of high cardiovascular risk (CVR), the proportion of people with high CVR who receive treatment and counseling, and to investigate the sociodemographic factors associated with this outcome, in Brazil. Methods: This was a cross-sectional study, using subsample data from the National Health Survey, collected via biochemical tests, in 2014-2015. Poisson regression was used. Results: The proportion of high CVR in men was 11.2% (95%CI 9.6;12.9), and 10.4% (95%CI 9.2;11.8%) in women. In the group with high CVR, 68.8% (95%CI 63.7;73.4%) received counseling, 59.3% (95%CI 54.2;64.3%) received medication, and 55.6% (95%CI 50.4;60.7%) received both. In the multivariate analysis, receiving treatment and counseling was associated with being aged 50 years and over, and poor/very poor self-rated health (PR=1.26 - 95%CI 1.06;1.51). Conclusion: The proportion of people with high CVR who had received treatment and counseling was over 50%.

Cardioprotective effect of taurine and ß-alanine against cardiac disease in myocardial ischemia and reperfusion-induced rats

BACKGROUND: The present study analyzed the synergistic protective effect of ß-alanine and taurine against myocardial ischemia/reperfusion. Myocardial infarct size, lipid peroxidation, and levels of glutathione peroxidase (Gpx), superoxide dismutase (SOD), reduced glutathione (GSH), catalase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), reactive oxygen species (ROS), apoptosis, and the mRNA and protein expression of Janus kinase 2 (JAK2) and signal transducer and activator 3 of transcription (STAT3) were determined. The molecular docking was carried out by using AutoDock 4.2.1. RESULTS: Combined treatment with ß-alanine and taurine reduced myocardial infarct size, lipid peroxidation, inflammatory marker, ROS levels, and apoptosis and increased Gpx, SOD activity, GSH, and catalase activity. Furthermore, combined treatment significantly reduced JAK2 and STAT3 mRNA and protein expression compared with the control. The small molecule was docked over the SH2 domain of a STAT3, and binding mode was determined to investigate the inhibitory potential of ß-alanine and taurine. ß-Alanine bound to SH2 domain with ΔG of -7.34 kcal/mol and KI of 1.91 µM. Taurine bound to SH2 domain with ΔG of -7.38 kcal/mol and KI of 1.95 µM. CONCLUSION: Taken together, these results suggest that the combined supplementation of ß-alanine and taurine should be further investigated as an effective therapeutic approach in achieving cardioprotection in myocardial ischemia/reperfusion.

Drug-related problems in cardiac neonates under intensive care / Problemas relacionados a medicamentos em neonatos cardiopatas sob terapia intensiva

ABSTRACT Objective: To determine the frequency and nature of the Drug Related Problems (DRP) in neonates with cardiac diseases admitted to an Intensive Care Unit. Methods: This prospective cross-sectional study was developed at the Neonatal Intensive Care Unit (NICU) of a teaching maternity hospital in Brazil from January 2014 to December 2016. All neonates diagnosed with any heart disease (congenital heart disease, cardiomyopathy, arrhythmias, etc.) and who were admitted to the NICU for more than 24 hours with at least one prescribed drug were included in the study. Demographic and clinical data were collected from the records of the institution's clinical pharmacy service. DRP and their respective interventions were independently reviewed and classified by two pharmacists. DRP classification was performed through the Pharmaceutical Care Network Europe v6.2 system. Results: 122 neonates were included in the study. The frequency of neonates exposed to DRP was 76.4% (confidence interval of 95% [95%CI] 65.9-82.0), with a mean of 3.2±3.8 cases/patient. In total, 390 DRP were identified, of which 49.0% were related to "treatment effectiveness", 46.7% to "adverse reactions" and 1.0% to "treatment costs". The medicines most involved in DRP were Vancomycin (10.2%; n=46), Meropenem (8.0%; n=36) and Furosemide (7.1%; n=32). Pharmacists performed 331 interventions, of which 92.1% were accepted by physicians and nurses. Conclusions: The study showed that DRP are very frequent in patients with cardiac diseases hospitalized in the NICU, predominating problems related to the effectiveness and safety of the drug treatment.

RESUMO Objetivo: Determinar a frequência e a natureza dos problemas relacionados a medicamentos (PRMs) em neonatos cardiopatas internados em uma unidade de terapia intensiva. Métodos: Trata-se de um estudo transversal prospectivo desenvolvido na Unidade de Terapia Intensiva Neonatal (UTIN) de uma maternidade de ensino do Brasil, de janeiro de 2014 a dezembro de 2016. Todos os neonatos diagnosticados com alguma doença cardíaca (cardiopatias congênitas, cardiomiopatias, arritmias etc.) e internados na UTIN por período superior a 24 horas, com pelo menos um medicamento prescrito, foram incluídos no estudo. Dados demográficos e clínicos foram coletados a partir dos registros do serviço de farmácia clínica da instituição. Os PRMs e suas respectivas intervenções foram revisadas e classificadas independentemente por dois farmacêuticos. A classificação dos PRMs foi realizada por meio do sistema Pharmaceutical Care Network Europe versão 6.2. Resultados: Cento e vinte e dois neonatos foram incluídos no estudo. A frequência de neonatos expostos a PRM foi de 76,4% (intervalo de confiança de 95% [IC95%] 65,9-82,0), com média de 3,2±3,8 casos por paciente. Ao todo, 390 PRM foram identificados, sendo que 49,0% estiveram relacionados à "efetividade do tratamento", 46,7% a "reações adversas" e 1,0% a "custos do tratamento". Os medicamentos mais envolvidos em PRM foram: vancomicina (10,2%; n=46), meropenem (8,0%; n=36) e furosemida (7,1%; n=32). Os farmacêuticos realizaram 331 intervenções, sendo 92,1% aceitas por médicos e enfermeiros. Conclusões: O estudo mostrou que PRMs são muito frequentes em pacientes cardiopatas internados em UTIN, predominando problemas relacionados à efetividade e segurança do tratamento medicamentoso.

TNF-alpha inhibitor adalimumab attenuates endotoxin induced cardiac damage in rats

Abstract Purpose To investigate the effects of adalimumab pretreatment on the lipopolysaccharide-mediated myocardial injury. Methods Twenty-eight Wistar rats were randomized into four groups (n=7). Control (C) group animals were injected once a day with intraperitoneal (i.p) 0.9 % saline for two days. In the Adalimumab (Ada) group, adalimumab was injected at a dose of 10 mg/kg/ day (i.p) for two days. Lipopolysaccharide (Lps) group rats were injected with a dose of 5 mg/kg (i.p) lipopolysaccharide. Lipopolysaccharide + Adalimumab (Lps+Ada) group rats received adalimumab before the administration of lipopolysaccharide. The animals were sacrificed 24 h after the last injection and blood samples were obtained for determination of biochemical cardiac injury markers and circulating levels of TNF-α and interleukin-6 (IL-6). Hearts were harvested for histological examination. Results Endotoxin exposure resulted in significant increases in serum cardiac injury markers, serum cytokines and histological myocardial injury scores in the Lps group. The levels of circulating cytokines, cardiac injury markers and histological injury scores for myocardial necrosis, perivascular cell infiltration, and inflammation were significantly reduced in Lps+Ada as compared to Lps group (p<0.05). Conclusions Adalimumab pretreatment reduces endotoxin-induced myocardial damage in rats. This beneficial effect is thought to be related to the reduction of cytokine release.

Interações medicamentosas em pacientes com eventos cardiovasculares e suas implicações para a segurança do paciente / Drug interactions in patients with cardiovascular events and their implications for patient safety

O objeto deste estudo é as potenciais interações medicamentosas em prescrições de pacientes hospitalizados com eventos cardiovasculares e sua associação com a ocorrência de eventos adversos relacionados a medicamentos. Para atender tal objeto, foram estabelecidos como objetivos: identificar as potenciais interações medicamentosas em pacientes hospitalizados com eventos cardiovasculares, considerando os horários estabelecidos para administração de medicamentos pelo enfermeiro; avaliar a ocorrência de eventos adversos a medicamentos associados às potenciais interações medicamentosas graves identificadas; e discutir a segurança no uso dos medicamentos, em vista o agendamento de horários para a administração dos medicamentos realizado pelo enfermeiro. Pesquisa de campo, quantitativa, seccional, documental. Foram analisadas 99 prescrições medicamentosas relativas às primeiras 48 horas de internação, obtidas dos prontuários de pacientes hospitalizados no período de abril a junho de 2014 num setor de cardiologia de um hospital público federal. Utilizou-se um instrumento estruturado para a coleta de dados demográficos e clínicos no prontuário e levantamento das medicações nas prescrições, as quais foram submetidas em pares de acordo com o horário agendado para administração pelo enfermeiro para análise no software Micromedex quanto à ocorrência de potenciais interações medicamentosas. Foi aplicada nesta análise estatística descritiva, medidas de tendência central e dispersão e cálculo de razão de chance. Para a identificação dos eventos adversos, realizou-se a análise dos prontuários de pacientes que apresentaram interações medicamentosas classificadas como graves, com o emprego de rastreadores específicos para eventos adversos adaptados. Os pacientes em que estes rastreadores foram identificados tiveram seu caso discutido por painel de especialistas para a definição da ocorrência do evento adverso, com base no emprego de um instrumento- síntese do caso e aplicação do Algoritmo de Naranjo para a análise da causalidade. Os resultados evidenciaram a prevalência do sexo masculino na amostra dos pacientes hospitalizados, com média de idade de 71,7 anos e diagnóstico principal de Insuficiência Cardíaca. Sobre o agendamento de horários, houve predomínio das 06 horas. No serviço diurno, o horário prevalente foi às 18 horas e no serviço noturno às 06 horas. A frequência da ocorrência de potenciais interações medicamentosas graves foi de 38,59%, com maior destaque para os pares sinvastatina + anlodipino e enoxaparina + clopidogrel. O consenso de especialistas classificou três casos prováveis de ocorrência de evento adversos associados às PIM grave. Os danos observados foram relacionados a eventos hemorrágicos e implicaram no prolongamento do tempo de internação desses pacientes. Os resultados da pesquisa em tela reiteram a discussão contemporânea das políticas públicas nacionais e internacionais em torno do uso seguro dos medicamentos. Os achados reiteram a importância do papel do enfermeiro na vigilância do uso dos medicamentos e direcionam ao debate das possíveis intervenções para a melhoria da segurança medicamentosa institucional, tais como o uso de tecnologias como subsídio para a tomada de decisão, o emprego de treinamentos teórico-práticos baseados na simulação realística da prática cotidiana do cuidar; que devem funcionar como barreiras de segurança e promover a qualidade da assistência na clínica do cuidado de enfermagem.

The object of this study is the potential drug interactions in prescriptions of patients hospitalized with cardiovascular events and its association with the occurrence of adverse events related to medications. To meet this object, were established as objectives: to identify potential drug interactions in hospitalized patients with cardiovascular events, considering the schedules established for administering medications by nurse to evaluate the occurrence of adverse drug events associated with potential identified serious drugs interactions; and discuss the safety in the use of medications, in view of scheduling schedules for the administration of the medications performed by the nurse. To evaluate the occurrence of adverse drug events associated with potential identified serious drugs interactions; and discuss the safety in the use of medications, in view of scheduling schedules for the administration of the medications performed by the nurse. Field research, quantitative, sectional, documentary. We analyzed 99 drug prescriptions for the first 48 hours of hospitalization, obtained from the medical records of hospitalized patients in the period from April to June 2014 in a cardiology sector of a federal public hospital. A structured instrument was used to collect demographic and clinical data in the medical records and to survey the medications in the prescriptions which were submitted in pairs according to the scheduled time for administration by the nurse for analysis Micromedex software regarding the occurrence of potential drug interactions. It was applied in this descriptive statistical analysis measures of central tendency and dispersion and calculation of odds ratio. For the identification of adverse events, we performed the analysis of the medical records of patients who presented drug interactions classified as severe, with the use of specific trackers for adapted adverse events. The patients in which these trackers were identified had their case discussed by panel of experts to define the occurrence of the adverse event based on the use of an instrument-synthesis of the case and application of the Naranjo algorithm for causality analysis. The results evidenced the prevalence of males in the sample of hospitalized patients with a mean age of 71.7 years and a major diagnosis of heart failure. On scheduling times, there was a predominance of 6 hours. In the daytime service, the prevailing time was at 18 hours and at night service at 6 hours. The frequency of the occurrence of potential serious drug interactions was 38.59%, with greater emphasis on the Simvastatin + Amlodipine and Enoxaparin + Clopidogrel pairs. The consensus of specialists classified three probable cases of occurrence of adverse events associated with severe PIM. The observed damage was related to hemorrhagic events and implied the prolongation of hospitalization time of these patients. The results of the research on the screen reiterate the contemporary discussion of national and international public policies around the safe use of medications. The findings reiterate the importance of the role of the nurse in the surveillance of medication use and direct the discussion of possible interventions to improve the institutional drug safety, such as the use of technologies as a subsidy for the taking of decision, the use of theoretical-practical training based on the realistic simulation of the daily practice of care; That should function as safety barriers and promote the quality of care in the nursing care clinic.

Evaluation of facial morphology and sagittal relationship between dental arches in primary and mixed dentition

OBJECTIVE: To assess facial morphology (Pattern) and sagittal relationship between dental arches (Class), and establish a potential association between them and the variables sex, age and ethnicity, among schoolchildren aged between 4 and 9 years old (mean age of 6.7 years) in primary and mixed dentitions.METHODS: The sample comprised 875 children (457 males and 418 females) attending schools in Descalvado, São Paulo, Brazil. An attempt was made with a view to establish a potential association between children's morphological features with sex, age and ethnicity.RESULTS: Descriptive analysis revealed a predominance of facial Pattern I (69.9 %) and Class I (67.4 %). Statistical tests (p < 0.001) showed that Class I was more frequent among Pattern I children, whereas Class II prevailed among Pattern II, and Class III was frequent among Pattern I and III children. Ethnicity was the only variable associated with facial pattern.CONCLUSIONS: Results suggest that facial pattern and sagittal relationship between dental arches tend to be correlated. Ethnicity was associated with facial pattern, with Pattern I being the most recurrent among Caucasians and facial Pattern II being recurrent among Afro-descendant subjects.

OBJETIVO: avaliar a morfologia facial (Padrão) e a relação sagital entre as arcadas dentárias (Classe) e determinar a associação entre sexo, idade e etnia, em escolares com 4 a 9 anos de idade (média de 6,7 anos), nas fases de dentadura decídua e mista.MÉTODOS: a amostra constou de 875 crianças (457 do sexo masculino e 418 do sexo feminino) de escolas do município de Descalvado/SP, que tiveram suas características morfológicas relacionadas ao sexo, idade e etnia.RESULTADOS: com base na análise descritiva dos dados, constatou-se que há predominância do Padrão I (69,9%) e da Classe I (67,4%). Nos testes estatísticos (p < 0,001), ficou evidente que a Classe I foi mais frequente no Padrão I; a Classe II, no Padrão II; e a Classe III, igualmente frequente nos Padrões I e III; apenas a raça teve associação com o padrão facial.CONCLUSÃO: o padrão facial e a relação sagital entre as arcadas dentárias tendem a estar relacionados, e a etnia tem associação com o padrão facial, sendo mais recorrente o Padrão I nos leucodermas e o Padrão II nos melanodermas.

Activador del plasminógeno tisular recombinante en el manejo de trombos cardiacos en recién nacidos / Recombinant tissue plasminogen activator for the management of intracardiac thrombi in newborns

Introducción: La incidencia de trombos cardíacos en recién nacidos (RN) ha aumentado con el uso de catéteres venosos centrales. La trombólisis con activador del plasminógeno tisular recombinante (rTPA) se ha utilizado como alternativa a la heparina en trombos gigantes con riesgo vital y de embolización. Nuestro objetivo fue describir la respuesta y las complicaciones relacionadas con el uso del rTPA en el manejo de trombos cardíacos con riesgo vital en RN. Pacientes y método: Estudio retrospectivo de 8 RN, 7 prematuros, con trombos cardíacos en los cuales se utilizó rTPA. Se analizó la edad gestacional y al diagnóstico, peso, sexo, enfermedades asociadas, hemograma, niveles de fibrinógeno, dímero D, tiempo parcial de tromboplastina activada y de protrombina, antes y al término de la infusión de rTPA. El diagnóstico del trombo se realizó por ecocardiografía doppler. La indicación de rTPA fue trombo mayor de 10 mm o que ocupara más del 50% de la cavidad donde se localizaba; aumento del tamaño a pesar del tratamiento con heparina, aspecto fragmentado y lobulado con riesgo embólico pulmonar o sistémico o que comprometiera la función valvular o cardíaca. Resultados: Cuatro hombres; peso promedio de 1.580 g. La principal enfermedad fue la sepsis (7/8), se usó catéter venoso central en todos, la vena cava superior fue la localización más frecuente, con tiempo promedio de instalación previo al diagnóstico de 12 días. En 7/8 RN los trombos se ubicaron en la aurícula derecha, con un tamaño entre 7 a 20 mm. Tres pacientes recibieron heparina de bajo peso molecular previo al uso de rTPA, se realizaron entre uno a 5 ciclos con rTPA. En 4 pacientes se logró resolución completa del trombo a los 3,5 días en promedio. No hubo embolia ni fallecidos. Cuatro pacientes presentaron hemorragia intracraneana grado I, sin secuelas en el seguimiento. Conclusión: Este estudio constituye la primera serie de neonatos tratados con rTPA en Chile, lográndose la resolución completa del trombo en un 50% de los RN y parcial en el resto, permitiendo con ello disminuir el riesgo vital secundario a este proceso patológico.

Introduction: The incidence of cardiac thrombi in newborns has increased with the use of central venous catheters. Thrombolysis with recombinant tissue plasminogen activator (rTPA) has been used as an alternative to heparin in life threatening giant thrombus and embolization. The aim of this study is to describe the response and complications related to the use of rTPA in the management of life- threatening cardiac thrombi in newborns. Patients and method: The medical records of 8 newborn were reviewed in a retrospective study, of whom 7 were preterm with cardiac thrombi, and rTPA was used in all of them. Results: The patients included 4 males with a mean weight of 1580 gr. The principal pathology was sepsis (7/8), all of them used venous central catheter. The superior vena cava was the most frequent location, with a mean time of installation before the diagnosis of 12 days. RN 7/8 thrombi were located in the right atrium with a size between 7 to 20 mm. Three patients received low molecular weight heparin prior to using rTPA. They received between 1 to 5 cycles with rTPA. In 4 patients complete resolution of the thrombus was achieved in a mean of 3.5 days. Four patients had intracranial haemorrhage grade I, without sequelae at follow-up. There were no deaths or embolism. Conclusion: This study is the first series of infants treated with rTPA in Chile, and where its use has quickly achieved complete resolution of the thrombus in 50% of cases, and partially in the others, thus reducing the secondary life-threatening risk of this disease.

Cardiología "basada en la evidencia": aplicaciones prácticas de la epidemiología. I. La valoración de medicamentos o terapias novedosas / Evidence-based cardiology: practical applications from epidemiology. I. The evaluation of a novel drug or therapy

El incremento sustancial de estudios terapéuticos que utilizan el diseño aleatorio controlado, demanda que el cardiólogo se familiarice con los aspectos esenciales en el diseño y conducción de los mismos, con énfasis particular en la interpretación adecuada y la aplicabilidad de sus resultados. En esta revisión basada en casos clínicos, se discuten algunos aspectos importantes en la valoración de terapia novedosa contemporánea como el uso y análisis de objetivos de eficacia compuestos; implicaciones de la terminación temprana de estudios y la extrapolación de resultados a la población.

The substantial increase of randomized controlled trials demand familiarity with the essential aspects of their design and performance by the cardiologist, particularly the adequate interpretation and applicability of the results. In this clinically-based review, we discuss some important aspects in the assessment of novel contemporary therapy such as the use and analysis of composite endpoints; implications from early termination of trials and extrapolation of results to the population.

Monitoring of anticoagulant therapy in heart disease: considerations for the current assays

Clinicians should be aware of new developments to familiarize themselves with pharmacokinetic and pharmacodynamic characteristics of new anticoagulant agents to appropriately and safely use them. For the moment, cardiologists and other clinicians also require to master currently available drugs, realizing the mechanism of action, side effects, and laboratory monitoring to measure their anticoagulant effects. Warfarin and heparin have narrow therapeutic window with high inter-and intra-patient variability, thereby the use of either drug needs careful laboratory monitoring and dose adjustment to ensure proper antithrombotic protection while minimizing the bleeding risk. The prothrombin time [PT] and the activated partial thromboplastin time [aPTT] are laboratory tests commonly used to monitor warfarin and heparin, respectively. These two tests depend highly on the combination of reagent and instrument utilized. Results for a single specimen tested in different laboratories are variable; this is mostly attributable to the specific reagents and to a much lesser degree to the instrument used. The PT stands alone as the single coagulation test that has undergone the most extensive attempt at assay standardization. The international normalized ratio [INR] was introduced to normalize-all PT reagents to a World Health Organization [WHO] reference thromboplastin preparation standard, such that a PT measured anywhere in the world would result in an INR value similar to that which would have been achieved had the WHO reference thromboplastin been utilized. However, INRs are reproducible between laboratories for only those patients who are stably anticoagulated with vitamin K antagonists [VKAs] [i.e., at least 6 weeks of VKA therapy], and are not reliable or reproducible between laboratories for patients for whom VKA therapy has recently been started or any other clinical conditions associated with a prolonged PT such as liver disease, disseminated intravascular coagulation, and congenital factor deficiencies. In contrast to marked progress in the standardization of PT reagents for INR reporting, no standardization system has been globally adopted for standardization of PTT reagents. Recently College of American Pathologists recommend that individual laboratories establish their own therapeutic range by using aPTT values calibrated against accepted therapeutic unfractionated heparin [UFH] levels calibrated against accepted therapeutic UFH levels performing anti-Xa test [which is the most accurate assay for monitoring UFH therapy]. Herein, we review recent data on the monitoring of conventional anticoagulant agents. Marked interlaboratory variability still exists for PT, INR, and PTT tests. Further research should be focused on improving the standardization and calibration of these assays

Drug therapy of cardiac diseases in children.

Justification: The indications and doses of most drugs used for heart ailments in children are extrapolated from data in adult patients. Separate guidelines are needed for neonates, infants and children because of the differences in underlying heart diseases and metabolic clearance of some of these drugs. Process: Consensus emerged following expert deliberations at the National Meeting on Management of Congenital Heart Diseases in India, held on 13th September 2008, at the All India Institute of Medical Sciences, New Delhi, India, supported by Pediatric Cardiac Society of India. Objectives: To review the literature and frame evidence based guidelines for (i) indications, doses, adverse effects and safety profile of commonly used drugs in pediatric cardiology practice; and (ii) to provide an algorithm for treatment in various clinical settings. Recommendations: Consensus review and recommendations are given for drugs used in children for heart failure, hypertension, thrombosis, supraventricular tachycardia and intensive care. Guidelines are also given for use of intravenous immunoglobulins and sildenafil in children.