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PURPOSE: Diffuse Brainstem Glioma (DBG) is a catastrophic brain tumor with a survival rate of less than 10% two years after diagnosis despite the existence of different treatment protocols. Among the devices that use magnetic fields generated by Magnetic Resonance Imaging is Quantum Magnetic Resonance Therapy (QMRT). METHODS: Five children diagnosed with DBG in our institution in Mexico City underwent treatment of compassionate use with QMRT between December 2018 and July 2019. A survival analysis was performed with previously reported historical data (n = 15). RESULTS: Two patients (40%) survived after three years of follow-up; the log-rank test showed a statistically significant difference in overall survival between both groups (p = 0.032). All patients tolerated the treatment adequately without reporting any severe clinical or neuroradiological adverse effects. Of the patients included, all showed a decrease in the tumor one month after the end of the treatment, although there was great variability in the response and the difference was not statistically significant (p = 0.06). CONCLUSIONS: Although future investigations are needed to confirm the findings reported in the present study, the improvement in survival is promising for a group of patients whose prognosis has been catastrophic over the years. Trial registration NCT03577600.
Assuntos
Neoplasias do Tronco Encefálico , Glioma , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/radioterapia , Criança , Ensaios de Uso Compassivo , Glioma/tratamento farmacológico , Glioma/terapia , Humanos , Campos Magnéticos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , MéxicoRESUMO
BACKGROUND: Epidemiological data from Mexico have documented an increase in heroin use in the last decade. However, there is no comprehensive care strategy for heroin users, especially those who have been accused of a crime. The objective of this study was to describe the heroin and methadone use of intravenous heroin users of both sexes who have been in jail, to offer evidence for the formulation of health policy. METHODS: This study used an ethnographic approach, with open-ended interviews carried out from 2014 to the present. Heroin users of both sexes attending a private methadone clinic in Mexico City were invited to participate. The sample was non-probabilistic. All interviews were audiotaped and transcribed, and narratives were analyzed using thematic analysis. RESULTS: Participants in this study were 33 users of heroin, two of them women, who had been in prison. They ranged in age from 33 to 62 years, had used heroin for a period of 13-30 years, and were from three states: Michoacan, Oaxaca, and Mexico City. Three principal categories of analysis were structured: 1. Pilgrimage for help (dynamics of the drama of suffering, pain, and time through health care spaces); 2) methadone use as self-care; and 3) accessibility to methadone treatment. The impossibility of access to methadone treatment is a condition which motivates users in their journey. The dynamics of methadone use are interpreted as a form of self-care and care to avoid substance use. Reducing the psychological, physical, and harmful effects of the substance allows them to perform daily activities. The inability to access treatment leads to a significant effect on users who experience structural violence. CONCLUSION: Compassionate methadone treatment and holistic attention should be considered as a way to meet patients' needs and mitigate their suffering, based on public health policy that allows for human rights-based care.
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Ensaios de Uso Compassivo , Dependência de Heroína , Adulto , Feminino , Dependência de Heroína/tratamento farmacológico , Dependência de Heroína/epidemiologia , Dependência de Heroína/psicologia , Humanos , Masculino , Metadona/uso terapêutico , México/epidemiologia , Pessoa de Meia-Idade , ViolênciaRESUMO
Introduction: Recently, researchers from China and France reported on the effectiveness of chloroquine and hydroxychloroquine for the inhibition of SARS-CoV-2 viral replication in vitro. Timely dissemination of scientific information is key in times of pandemic. A systematic review of the effect and safety of these drugs on COVID-19 is urgently needed. Objective: To map published studies until March 25, 2020, on the use of chloroquine and its derivates in patients with COVID-19. Materials and methods: We searched on PubMed, Embase, Lilacs, and 15 registries from the World Health Organization's International Clinical Trials Registry Platform for theoretical and empirical research in English, Spanish, Italian, French, or Portuguese until March 25, 2020, and made a narrative synthesis of the results. Results: We included 19 records and 24 trial registries (n=43) including 18,059 patients. China registered 66% (16/24) of the trials. Nine trials evaluate chloroquine exclusively and eight hydroxychloroquine. The records are comments (n=9), in vitro studies (n=3), narrative reviews (n=2), clinical guidelines (n=2), as well as a systematic review, an expert consensus, and a clinical trial. Conclusions: One small (n=26), non-randomized, and flawed clinical trial supports hydroxychloroquine use in patients with COVID-19. There is an urgent need for more clinical trial results to determine the effect and safety of chloroquine and hydroxychloroquine on COVID-19.
Introducción. Recientemente, investigadores chinos y franceses reportaron la eficacia de la cloroquina y la hidroxicloroquina para inhibir la replicación in vitro del virus SARS-CoV-2. La diseminación oportuna de la información científica es clave en tiempos de pandemia. Es urgente contar con una revisión sistemática sobre el efecto y la seguridad de estos medicamentos en la COVID-19. Objetivo. Describir el estado actual de la literatura científica publicada hasta el 25 de marzo de 2020 sobre el uso de la cloroquina o sus derivados en el manejo de pacientes con COVID-19. Materiales y métodos. Se hizo una revisión sistemática exploratoria en PubMed, Embase, Lilacs y 15 bases de datos de la Plataforma de Registros Internacionales de Ensayos Clínicos de la Organización Mundial de la Salud (OMS). Se incluyeron publicaciones empíricas y teóricas en inglés, español, italiano, francés o portugués, y se hizo una síntesis narrativa de los resultados. Resultados. Se incluyeron 19 documentos y 24 registros de ensayos clínicos (n=43) de 18.059 pacientes. El 66 % (16/24) de los ensayos están registrados en China. Nueve ensayos evalúan la cloroquina exclusivamente y ocho, la hidroxicloroquina. Los documentos son comentarios (n=9), estudios in vitro (n=3), revisiones narrativas (n=2), guías de práctica clínica (n=2), así como una revisión sistemática, un consenso de expertos y un ensayo controlado. Conclusiones. Un ensayo clínico pequeño (n=26), no aleatorizado y defectuoso, respalda el uso de la hidroxicloroquina en pacientes con COVID-19. Se requiere de manera urgente tener acceso a los resultados de otros ensayos clínicos para determinar la efectividad y la seguridad de la cloroquina y sus derivados en pacientes con COVID-19.
Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Antivirais/efeitos adversos , Antivirais/farmacologia , Betacoronavirus/fisiologia , COVID-19 , Cloroquina/efeitos adversos , Cloroquina/farmacologia , Ensaios Clínicos como Assunto , Ensaios de Uso Compassivo , Síndrome da Liberação de Citocina/tratamento farmacológico , Reposicionamento de Medicamentos , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/farmacologia , Estudos Multicêntricos como Assunto , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , SARS-CoV-2 , Resultado do Tratamento , Replicação Viral/efeitos dos fármacos , Tratamento Farmacológico da COVID-19RESUMO
The COVID-19 pandemic has affected 187 countries, representing a global public health problem. The increasing number of critically ill patients and deaths have fueled a desperate search for treatments that can halt the course of the disease. Currently, there are several experimental therapies with demonstrated in vitro activity against COVID-19 used in clinical practice, including hydroxychloroquine, remdesivir, interleukin-6 pathway inhibitors, and convalescent plasma; however, to date no agent has proven efficacy against COVID-19. In the case of convalescent plasma, this therapy consists in obtaining neutralizing antibodies from previously infected individuals by plasmapheresis and administering them to patients with severe disease. Recently, the use of convalescent plasma has shown promising results in preliminary studies, with case series reporting a decrease in temperature, and viral load, as well as improvement in clinical parameters among patients receiving this treatment. However, there are still unmet needs regarding the safety profile, tolerability, dosage, and timing this therapy should be given. Based on this, the objective of our study was to develop and propose a practical approach for the compassionate use of convalescent plasma for the treatment of patients with severe COVID-19, given the constrains and limitations of developing countries. We encourage health professionals in developing countries to use the current evidence and approaches to experimental treatments for patients with COVID-19, adapting them to their conditions, and always based on a thorough risk-benefit evaluation for each patient, and whenever possible to design and promote the much needed research in this field.
Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Assistência ao Convalescente , COVID-19 , Ensaios de Uso Compassivo , Infecções por Coronavirus/etiologia , Estado Terminal , Países em Desenvolvimento , Humanos , Imunização Passiva , Pandemias , Seleção de Pacientes , Plasmaferese , Pneumonia Viral/etiologia , SARS-CoV-2 , Soroterapia para COVID-19RESUMO
BACKGROUND: The COVID-19 pandemic outbreak has set the emergency services in developing countries on major alert, as the installed response capacities are easily overwhelmed by the constantly increasing high demand. The deficit of intensive care unit beds and ventilators in countries like Peru is forcing practitioners to seek preventive or early interventional strategies to prevent saturating these chronically neglected facilities. CASE PRESENTATION: A 64-year-old patient is reported after presenting with COVID-19 pneumonia and rapidly progressing to deteriorated ventilatory function. Compassionate treatment with a single 1Gy dose to the bilateral whole-lung volume was administered, with gradual daily improvement of ventilatory function and decrease in serum inflammatory markers and oxygen support needs, including intubation. No treatment-related toxicity developed. Procedures of transport, disinfection, and treatment planning and delivery are described. CONCLUSION: Whole-lung low-dose radiotherapy seems to be a promising approach for avoiding or delaying invasive respiratory support. Delivered low doses are far from meeting toxicity ranges. On-going prospective trials will elucidate the effectiveness of this approach.
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Tratamento Farmacológico da COVID-19 , COVID-19/radioterapia , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , COVID-19/sangue , COVID-19/diagnóstico por imagem , COVID-19/terapia , Terapia Combinada , Ensaios de Uso Compassivo , Enoxaparina/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxigenoterapia , Peru , Planejamento da Radioterapia Assistida por Computador , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: CIGB-247 is a cancer therapeutic vaccine that uses as antigen a variant of human vascular endothelial growth factor (VEGF) mixed with the bacterially-derived adjuvant VSSP. CIGB-247 has been already evaluated in two phase I clinical trials (CENTAURO and CENTAURO-2), showing to be safe and immunogenic in advanced cancer patients selected under well-defined and controlled clinical conditions. Surviving patients were submitted to monthly re-immunizations and some of them showed objective clinical benefits. Based on these results, a compassionate use program (CUP) with CIGB-247 was initiated for patients that did not meet the strict entry criteria applied for the CENTAURO and CENTAURO-2 clinical trials, but could potentially benefit from the application of this cancer therapeutic vaccine. RESULTS: Polyclonal IgM, IgA and IgG antibodies specific for VEGF were detected by ELISA in serum samples from patients vaccinated with 400 µg of antigen combined with 200 µg of VSSP. Polyclonal antibody response showed no cross reactivity for other VEGF family member molecules like VEGF-C and VEGF-D. Serum from immunized individuals was able to block the binding of VEGF to its receptors VEGFR2 and VEGFR1. IgG fraction purified from immune sera shared the aforementioned characteristics and also inhibited the interaction between VEGF and the therapeutic recombinant antibody bevacizumab, an anti-angiogenic drug approved for the treatment of different tumors. No serious adverse events attributable to CIGB-247 have been documented yet in participants of the CIGB-247 CUP. The present paper is a first report of our findings concerning the humoral response and safety characteristics in treated CIGB-247 CUP cancer patients. The study has provided the unique opportunity of not only testing CIGB-247 in a broader clinical spectrum sample of Cuban cancer patients, but also within the context of the day-to-day clinical practice and treatment settings for these diseases in Cuban medical institutions. CONCLUSIONS: The CIGB-247 CUP has demonstrated that immunization and follow-up of a variety of cancer patients, under day-to-day clinical practice conditions in several Cuban medical institutions, replicate our previous findings in clinical trials: CIGB-247 is safe and immunogenic.
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Vacinas Anticâncer/imunologia , Imunoterapia Ativa/métodos , Neoplasias/imunologia , Proteolipídeos/imunologia , Fator A de Crescimento do Endotélio Vascular/imunologia , Adjuvantes Imunológicos , Ensaios de Uso Compassivo , Feminino , Humanos , Imunidade Humoral , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Resultado do Tratamento , Vacinação , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
En los últimos años, se ha observado un incremento significativo en el interés por la prescripción del cannabis medicinal. En el siguiente artículo, se informa acerca de la escasa base científica que avala la prescripción de estos compuestos en un listado amplio y diverso de patologías médicas. Se considera fundamental que cualquier sustancia que vaya a ser utilizada en humanos siga un protocolo de aprobación estricto y científico, que pueda desligarse de modas o de resultados individuales. Es necesario que, antes de la prescripción de una droga en personas, deba tenerse un panorama claro de cuáles son los usos del compuesto en cuestión, pero, sobre todo, de su seguridad, que es prácticamente desconocida en el cannabis medicinal.
In recent years, the interest in medical cannabis prescription has increased significantly. This article provides information about the little scientific basis supporting the prescription of these products for a wide and diverse range of medical conditions. It is critical for any substance to be used in human beings to follow a strict scientific approval protocol, detached from any trend or individual outcome. Before prescribing any drug to human beings, it is necessary to have a clear picture of its uses, especially its safety, which is practically unknown in the case of medical cannabis.
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Humanos , Canabidiol/efeitos adversos , Canabidiol/uso terapêutico , Maconha Medicinal/efeitos adversos , Maconha Medicinal/uso terapêutico , Segurança , Dronabinol/uso terapêutico , Canabidiol/farmacologia , Ensaios de Uso Compassivo , Legislação de MedicamentosRESUMO
INTRODUCTION AND OBJECTIVES: Direct antiviral agents (DAAs) are very efficient in inhibiting hepatitis C virus and might be used to treat infections caused by other flaviviruses whose worldwide detection has recently increased. The aim of this study was to verify the efficacy of DAAs in inhibiting yellow fever virus (YFV) by using drug repositioning (a methodology applied in the pharmaceutical industry to identify new uses for approved drugs). MATERIALS AND METHODS: Three DAAs were evaluated: daclatasvir, sofosbuvir and ledipasvir or their combinations. For in vitro assays, the drugs were diluted in 100% dimethyl sulfoxide. Vaccine strain 17D and a 17D strain expressing the reporter fluorescent protein were used in the assays. A fast and reliable cell-based screening assay using Vero cells or Huh-7 cells (a hepatocyte-derived carcinoma ell line) was carried out. Two patients who acquired yellow fever virus with acute liver failure were treated with sofosbuvir for one week as a compassionate use. RESULTS: Using a high-content screening assay, we verified that sofosbuvir presented the best antiviral activity against YFV. Moreover, after an off-label treatment with sofosbuvir, the two female patients diagnosed with yellow fever infection displayed a reduction in blood viremia and an improvement in the course of the disease, which was observed in the laboratory medical parameters related to disease evolution. CONCLUSIONS: Sofosbuvir may be used as an option for treatment against YFV until other drugs are identified and approved for human use. These results offer insights into the role of nonstructural protein 5 (NS5) in YFV inhibition and suggest that nonstructural proteins may be explored as drug targets for YFV treatment.
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Antivirais/farmacologia , Benzimidazóis/farmacologia , Fluorenos/farmacologia , Imidazóis/farmacologia , Sofosbuvir/farmacologia , Febre Amarela/tratamento farmacológico , Vírus da Febre Amarela/efeitos dos fármacos , Animais , Antivirais/uso terapêutico , Carbamatos , Linhagem Celular Tumoral , Chlorocebus aethiops , Ensaios de Uso Compassivo , Reposicionamento de Medicamentos , Feminino , Humanos , Técnicas In Vitro , Falência Hepática Aguda/etiologia , Pirrolidinas , Sofosbuvir/uso terapêutico , Valina/análogos & derivados , Células Vero , Carga Viral/efeitos dos fármacos , Proteínas não Estruturais Virais/antagonistas & inibidores , Febre Amarela/complicaçõesRESUMO
[RESUMO]. Objetivo. Descrever e comparar os marcos regulatórios das políticas de acesso rápido/alternativo a medicamentos (acesso expandido e uso compassivo) em países da América do Sul. Métodos. Realizou-se um estudo exploratório e descritivo, com análise documental. Além de revisão da literatura científica sobre o tema, foram levantadas informações e normas oficiais caso estivessem disponíveis nas páginas eletrônicas das autoridades reguladoras de medicamentos. Foram coletadas informações sobre a forma como cada país define os conceitos de acesso expandido e uso compassivo, fase clínica em que o medicamento fica disponível para esses usos alternativos e obrigações de médicos e patrocinadores. Resultados. A partir dos critérios de inclusão, foram selecionados para o estudo Argentina, Brasil, Chile, Peru e Uruguai. O levantamento de informações mostrou que Argentina e Brasil apresentam um cenário regulatório mais estruturado. O Chile apresenta uma norma sobre acesso expandido e uso compassivo, porém sem definir explicitamente esses conceitos. No Peru e Uruguai, foi constatada a ausência de definições importantes quanto ao acesso expandido. Não foram identificadas quaisquer bases de dados com informações sobre acesso expandido e uso compassivo, corroborando a percepção de escassez de dados empíricos para avaliar os resultados dessas políticas. Conclusões. Todos os países analisados contam com um marco regulatório que permite o acesso rápido/ alternativo a medicamentos por pacientes em situação de risco. Porém, não existem bancos de dados e transparência de informações que permitam caracterizar quais medicamentos e pacientes se beneficiam desse acesso alternativo e avaliar os resultados dessas políticas na América do Sul.
[ABSTRACT]. Objective. To describe and compare the regulatory framework governing policies on rapid/alternative access to medicines (expanded access and compassionate use) in South American countries. Method. An exploratory descriptive study with analysis of documents was performed. In addition to a literature review, official rules issued by regulatory agencies were reviewed if available. Information was collected on how countries define the concepts of expanded access and compassionate use, clinical phase in which the medicine becomes available for these alternative uses, and role of physicians and sponsors. Results. Argentina, Brazil, Chile, Peru, and Uruguay were included in the study. The information obtained revealed that the regulatory scenario is more structured in Argentina and Brazil than in the other countries. In Chile, rules on expanded access and compassionate use are available, however without an explicit definition of these concepts. In Peru and Uruguay, important definitions are missing regarding expanded access. The search did not reveal any databases with information on expanded access and compassionate use programs, supporting the notion that empirical data to evaluate the results of these policies are lacking. Conclusions. All the countries analyzed have a regulatory framework that contemplates rapid/alternative access to medicines by patients at risk. However, databases and transparent information are lacking, preventing a snapshot of the medicines covered and patients benefiting from alternative access programs and assessments of these policies in South America.
[RESUMEN]. Objetivo. Describir y comparar los marcos regulatorios de las políticas de acceso rápido y alternativo a medicamentos (acceso ampliado y uso compasivo) en países de América del Sur. Métodos. Se realizó un estudio exploratorio y descriptivo, con análisis documental. Además de revisión de la bibliografía científica sobre el tema, se obtuvo información sobre las normas oficiales, si estaba disponible en las páginas electrónicas de las autoridades regulatorias de medicamentos. Se recolectó información sobre la forma en que cada país define los conceptos de acceso ampliado y uso compasivo, la fase clínica en que se ofrece el medicamento para uso alternativo y las obligaciones de los médicos y patrocinadores. Resultados. A partir de los criterios de inclusión, se seleccionaron para el estudio Argentina, Brasil, Chile, Perú y Uruguay. La información obtenida mostró que Argentina y Brasil presentan un escenario regulatorio más estructurado en comparación con los demás países del grupo citado. Chile presenta una norma sobre acceso ampliado y uso compasivo, pero sin definir explícitamente esos conceptos. En Perú y Uruguay, se constató la falta de definiciones importantes en cuanto al acceso ampliado. No se encontraron bases de datos con información sobre acceso ampliado y uso compasivo, lo cual corroboró la percepción sobre la escasez de datos empíricos para evaluar los resultados de esas políticas. Conclusiones. Todos los países analizados cuentan con un marco regulatorio que permite el acceso rápido y alternativo a medicamentos de los pacientes en situación de riesgo. Sin embargo, no existen bancos de datos ni información transparente que permitan determinar qué medicamentos y pacientes se benefician de ese acceso alternativo y evaluar los resultados de esas políticas en América del Sur.