Chronic lymphocytic leukemia: a clinical review including Korean cohorts

Only 5th decade ago, chronic lymphocytic leukemia (CLL) was only recognized as disease group of presenting features like peripheral lymphocytosis, organomegaly including of splenomegaly. As understanding of disease biology and molecular diagnostic tools are getting improved gradually, characterization of variation in CLL's clinical courses was facilitated, resulting in better risk stratification and targeted treatments. Consequently multiple new targeted agents have been used in treatment of CLL, it makes improved clinical outcome. Rituximab containing chemoimmunotherapy (combination of rituximab, fludarabine, and cyclophosphamide) have shown better overall response rate and progression-free survival on fit patients' group in front-line setting, result in standard first-line therapeutic option for CLL. Furthermore, after introducing that the B-cell receptor is crucial for the evolution and progression of CLL, emerging treatments targeting highly activated surface antigens and oncogenic signaling pathways have been associated with several successes in recent decades. These include new anti-CD 20 monoclonal antibody (obinutuzumab), the bruton tyrosine kinase inhibitor (ibrutinib), the phosphatidylinositol 3-kinase inhibitor (idelalisib), and B-cell CLL/lymphoma 2 inhibitor (ABT-199 and ABT-263). So, we discuss not only general pathophysiology of CLL, but also rapidly advancing treatment strategies that are being studied or approved for treatment of CLL.

Prescripción de Medicaciones no aprobadas (off label y sin licencia) en Recién Nacidos hospitalizados. Estudio multicéntrico en cinco hospitales de Asunción y Gran Asunción / Prescription of Off-label and Unlicensed Drugs in Hospitalized Newborns: a Multicenter Study in Five Hospitals in Greater Asuncion, Paraguay

Introducción: La falta de suficientes estudios clínicos sobre la eficacia y seguridad de las medicaciones en la población neonatal, conduce a la utilización de alternativas con medicaciones no aprobadas. Objetivos: Determinar la prevalencia de la utilización de medicaciones no aprobadas por la Food and Drug Administration (EEUU) en los neonatos hospitalizados en diferentes niveles de atención de cinco hospitales de Asunción y Gran Asunción. Metodología: Estudio observacional, descriptivo con componente analítico, transversal. Se incluyeron recién nacidos de las salas de terapia intensiva, intermedia y cuidados mínimos de cinco hospitales. Variables: Peso de nacimiento, edad gestacional, sexo, vía del parto, edad postnatal al ingreso al estudio, sala de internación, asistencia respiratoria mecánica y tipo y número de medicaciones no aprobadas (MNA) por paciente en el momento de llenarse el cuestionario. Los datos fueron cargados y analizados en SPSS 17 y se expresaron en proporciones y medias. Se utilizó la prueba de chi cuadrado y se consideró un error alfa del 5%. Resultados: Se analizaron 105 pacientes con edad postnatal al ingreso al estudio de 12±8 días y 11±8 días de hospitalización. Recibieron MNA 41 neonatos (39%) con 92 prescripciones no autorizadas, en mayor proporción en la unidad de terapia intensiva (49%), con respecto a las salas de los otros niveles (p=0,01). El número de MNA por neonato fue de 2,29±1,7 (rango1 a 8). Las MNA más frecuentemente utilizadas fueron antibióticos (42%), omeprazol y ranitidina (11%) y los corticoides (9%). Conclusiones: La prevalencia de utilización de medicaciones no aprobadas fue elevada y se demostró asociación con el uso de asistencia respiratoria mecánica y presencia de infecciones .

Introduction: The scarcity of clinicalstudies on the efficacy and safety ofmedications in newborns leads tothe use of alternative treatment using unapproved drugs...

Ideas and methods of fresh herb basic research based on constituent structure theory / 中国中药杂志

Application of fresh herbs is a kind of special forms of traditional Chinese medicine. In China, there is a long and rich experience in clinical application of fresh herbs. Many studies showed that the efficacy of fresh herbs was better than that of dried herbs, but the further study about the difference of their chemical composition, effective components and the overall material basis were few. In this paper, the ideas and methods to study on material basis of the fresh herbs by comparing the difference of the fresh and dry herbs in medicine chemical composition and pharmacological activity of effective components with modern advanced separation, analysis and screening technology under the "Constituent structure theory" were proposed. It was an effectual method for studying on the reasonable development of Chinese medicine and fresh herbs resources.

Reflexão histórico-epistemológica sobre os fundamentos epidemiológicos da Clínica Médica contemporânea / Historical and epidemiological reflections about the epidemiologic foundations of contemporary Clinical Medicine

A medicina clínica apresentou a partir dos anos 1960 uma certa inflexão em seus mecanismos internos de produzir conhecimento, assim como em sua forma de aplicar esses conhecimentos na prática. A principal diferença em relação ao passado foi que, a partir dessa época, os problemas de natureza clínica, como diagnóstico diferencial, terapêutica e estimativa de prognóstico, passaram a ser processados predominantemente por instrumentos de análise padronizados e, principalmente, submetidos ao escrutínio de uma razão empírico-matemática. A entidade paciente deixou de ser um ente emissor de sintomas e sinais que são processados por um médico, para ser uma nova entidade em que esses signos, previamente estabelecidos e validados pelos estudos clínicos e pela razão matemática, são encaixados pelos médicos nas manifestações dos pacientes. Na mesma época em que esse processo ocorreu o mundo ocidental vivia um período de crise que se caracterizava por um baixo crescimento econômico e por um questionamento por parte da sociedade dos princípios normativos, tanto éticos quanto morais, que regiam sua forma de viver. Nos Estados Unidos, a partir de 1962 passou a ser uma exigência legal que toda droga nova, antes de ser comercializada, deveria provar, através de testes científicos, que ela tinha eficácia terapêutica, que de fato funcionava na patologia que se propunha tratar. A metodologia para promover esse tipo de demonstração foi construída a partir dessa exigência. As regras de prova científica de eficácia foram construídas a partir dessa demanda legal, e são chamadas genericamente de Epidemiologia Clínica. Vários agentes participaram ativamente do processo de definição das regras do método científico que foram então, a partir dessa data, implementadas e sedimentadas. Destacam-se nesse debate, a comunidade acadêmica, a sociedade civil, os economistas, os advogados e juizes, os agentes do governo, e, finalmente, a indústria farmacêutica...

Since 1960 Clinical Medicine suffered a kind of inflection in its internal mechanisms of producing theoretical knowledge, as well as in the way that this knowledge is applied in practical life. The most important difference in relation to the past was that problems of clinical nature like, differential diagnosis, therapeutical decisions, and prognosis estimation, started to be predominantly processed by standardized analytical instruments, and most important, they were always previously submitted to an empirical-mathematical reasoning. Individual patients were no longer a being that reported signs and symptoms that were processed by a physician, they started to be a new entity in which these signs, previously established and validated by clinical studies have to be necessarily engrafted by the physicians in patients manifestations. At the same time that this process occurred, western world was living an important critical period, characterized by a very slow economic growth, and by a reevaluation of its ethical and moral values. After 1962, in the United States, it became obligatory to prove, through empirical scientific evidence that a new drug was effective, before marketing and sales authorization was issued to a company who wanted to launch the drug. The scientific method designed to prove efficacy of a drug was actually developed after this legal demand. This method is called generically Clinical Epidemiology. Several actors participated in the discussion of the rules of this method. Medical Schools, government representatives, pharmaceutical industry can be cited; the latter played a very special role, since it acted as a secretary of the whole process. The reason behind this was that, at those times, the two major pillars of the pharmaceutical business, innovation capacity and patent law, were being severely criticized, and proposals for changing the way this things were being conducted in American society were about to become a reality...

O uso de drogas ainda experimentais em assistência: extensão de pesquisa, uso compassivo e acesso expandido / Therapeutic uses of investigational drugs: research extension, compassionate use, and expanded access

O presente artigo descreve os aspectos metodológicos, regulatórios e éticos das diferentes formas de acesso a drogas ainda experimentais em situações assistenciais - extensão de pesquisa, uso compassivo e acesso expandido. Em todo o mundo, essa modalidade de assistência tem como principais desafios o estabelecimento de critérios mínimos de qualificação tanto dos pesquisadores quanto das instituições para que possam realizar projetos envolvendo novas drogas em suas diferentes fases, a capacitação dos membros dos comitês de avaliação de projetos quanto aos aspectos metodológicos, regulatórios e éticos envolvidos na pesquisa de novas drogas, a explicitação das relações entre pesquisadores e patrocinadores e entre pesquisadores e participantes da pesquisa e a oposição quanto à recente proposta de possibilitar aos fabricantes de medicamentos a cobrança pelas drogas utilizadas em projetos de pesquisa.

This article describes the methodological, regulatory, and ethical aspects of the different therapeutic uses of investigational drugs-research extension, compassionate use, and expanded access. Worldwide, the principle challenges of this kind of treatment are: setting minimum quality standards for researchers, as well as institutions, so that projects can include drugs at various stages of development; training of evaluation and assessment committees on the methodological, regulatory, and ethical aspects of new drug research; clearly outlining the relationship between researchers and funding organizations and between researchers and study participants; and understanding the opposition to the recent proposal to enable drug manufacturers to charge for drugs used in research studies.

Definições, conceitos e aspectos operacionais utilizados em farmacovigilância / Definitions, concepts and operational aspects utilized in drug surveillance

O artigo expõe definições e conceitos utilizados na área de farmacovigilância, métodos de pesquisa para a identificação de reações adversas a medicamentos, notificação e organização de sistemas de farmacovigilância. De modo geral, as ações de farmacovigilância assumem dois aspectos diversos conforme o objetivo a ser atingido: (i) ações dos profissionais de saúde, que mantêm contato direto com o paciente e (ii) organização de sistemas de coleta, análise, processamento de informaçao e disseminação dos resultados, que incluem os sistemas nacionais de farmacovigilância e o Centro Colaborativo de Monitorização Internacional de Medicamentos da Organização Mundial da Saúde. Para se estabelecer a verdadeira...

Principios de la bioética en la investigación del surfacén en recién nacidos prematuros / Bioethic principles in the investigation of surfacen in premature new born infants

Se hace un análisis desde el punto de vista de los principios de la bioética, sobre la investigación en la fase III de ensayo clínico de la aplicación del surfacén para el síndrome de dificultad respiratoria del recién nacido, la cual se llevó a efecto en Cuba. El colectivo de investigadores tuvo que enfrentar una serie de disyuntivas bioéticas que pusieron de manifiesto la integridad de ese colectivo. Se demuestra que los principios de la bioética: beneficiencia, no mal eficiencia, autonomía y justicia, se tuvieroon en cuenta en el protocolo de la investigación y durante la ejecución de ésta. Según este análisis, se justifica que se tomara un grupo control histórico, en lugar de un grupo control placebo, para las comparaciones de la utilización del surfacén y que se optara por el consentimiento parental después de una información verbal por el médico, sin necesidad de utilizar un documento de consentimiento escrito

Levels of DDT and metabolites in breast milk from Kwa-Zulu mothers after DDT application for malaria control

Concentrations of DDT, DDE and DDD were determined in the breast milk of Kwa-Zulu mothers residing in two different areas--with and without annual intra-domiciliary applications of DDT for the interruption of malaria transmission (exposed and control groups, respectively). While no significant change in levels with time was found in the control group, both DDT and DDE in breast milk of the exposed group increased after DDT application and this continued for three more months, after which it did not decrease appreciably. Percentage DDT increased from 42.57% (sigma DDT = 12.21 mg/kg milk fat) before spraying to 50.87% (sigma DDT = 13.79 mg/kg milk fat) following DDT application. At 6 and 9 months after the application it was 45.85% (sigma DDT = 19.49 mg/kg milk fat) and 43.27% (sigma DDT = 18.34 mg/kg milk fat), respectively. These results suggest a risk to the health of the infants in the exposed group