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BACKGROUND: The Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is the target for many COVID-19 vaccines. Here we report results for phase I clinical trial of two COVID-19 vaccine candidates based on recombinant dimeric RBD (d-RBD). METHODS: We performed a randomized, double-blind, phase I clinical trial in the National Centre of Toxicology in Havana. Sixty Cuban volunteers aged 19-59 years were randomized into three groups (20 subjects each): 1) FINLAY-FR-1 (50 µg d-RBD plus outer membrane vesicles from N. meningitidis); 2) FINLAY-FR-1A-50 (50 µg d-RBD, three doses); 3) FINLAY-FR-1A-25 (25 µg d-RDB, three doses). The FINLAY-FR-1 group was randomly divided to receive a third dose of the same vaccine candidate (homologous schedule) or FINLAY-FR-1A-50 (heterologous schedule). The primary outcomes were safety and reactogenicity. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following each vaccination was evaluated using live-virus neutralization test, anti-RBD IgG ELISA and in-vitro neutralization test of RBD:hACE2 interaction. RESULTS: Most adverse events were of mild intensity (63.5%), solicited (58.8%), and local (61.8%); 69.4% with causal association with vaccination. Serious adverse events were not found. The FINLAY-FR-1 group reported more subjects with adverse events than the other two groups. After the third dose, anti-RBD seroconversion was 100%, 94.4% and 90% for the FINLAY-FR-1, FINLAY-FR-1A-50 and FINLAY-FR-1A-25 respectively. The in-vitro inhibition of RBD:hACE2 interaction increased after the second dose in all formulations. The geometric mean neutralizing titres after the third dose rose significantly in the group vaccinated with FINLAY-FR-1 with respect to the other formulations and the COVID-19 Convalescent Serum Panel. No differences were found between FINLAY-FR-1 homologous or heterologous schedules. CONCLUSIONS: Vaccine candidates were safe and immunogenic, and induced live-virus neutralizing antibodies against SARS-CoV-2. The highest values were obtained when outer membrane vesicles were used as adjuvant. TRIAL REGISTRY: https://rpcec.sld.cu/en/trials/RPCEC00000338-En.

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Introducción: En 1967 se estableció, por primera vez, un comité de monitoreo de datos, en un estudio de mortalidad cardiovascular; desde entonces su uso se ha incrementado debido a su valor para garantizar la seguridad de los sujetos participantes en ensayos clínicos y la validez e integridad de los datos. Se realizó una exploración documental de los últimos 20 años, sobre aspectos relacionados con los requisitos de creación y funcionamiento de los comités de monitoreo de datos a nivel mundial, con los objetivos de mostrar el desarrollo alcanzado en el establecimiento de los comités de monitoreo de datos e identificar sus características fundamentales. Desarrollo: Existe un incremento en la producción documental sobre los comités de monitoreo de datos, liderado por angloparlantes de países desarrollados, con franco aumento de publicaciones sobre el tema en el último quinquenio, superior en 50 por ciento a los 15 años anteriores. Este fenómeno lo provoca el auge de la industria farmacéutica y biotecnológica, los altos costos de investigación y desarrollo de medicamentos, la necesidad de introducir nuevos fármacos y el incremento de las exigencias regulatorias. Se describen las características estructurales, requisitos clínicos y metodológicos para el establecimiento de los comités. Conclusiones: Existe alto desarrollo de los comités de monitoreo de datos en los ensayos clínicos, con tendencia al incremento de su uso en los últimos años. Los comités de monitoreo de datos se caracterizan por requerimientos clínicos y metodológicos para su establecimiento(AU)

Introduction: For the first time, in 1967, a data monitoring committee was established in a study of cardiovascular mortality. Since then its use has increased, due to its value to guarantee the safety of subjects participating in clinical trials, the validity and integrity of the data. A documentary exploration of the last 20 years was carried out, on aspects related to the requirements for the creation and operation of data monitoring committees worldwide, with the aim of showing the development achieved in the establishment of data monitoring committees and identify its fundamental characteristics. Development: There is an increase in documentary production on data monitoring committees, led by English speakers from developed countries, with a clear increase in publications on the subject, in the last five-year period, 50% higher than in the previous 15 years. This phenomenon is caused by the rise of the pharmaceutical and biotechnology industry, the high costs of drug research and development, the need to introduce new drugs and the increase in regulatory requirements. The structural characteristics, clinical and methodological requirements for the establishment of the committees are described. Conclusions: There is a high development of data monitoring committees in clinical trials, with a tendency to increase their use in recent years. Data monitoring committees are characterized by clinical and methodological requirements for their establishment(AU)

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El consentimiento informado es un proceso que consiste en un diálogo entre los investigadores y el paciente, acerca de determinado procedimiento relativo a su salud. En los ensayos clínicos, el consentimiento informado tiene una connotación especial por tratarse de una investigación en la cual puede buscarse la eficacia y seguridad de un nuevo producto. Los principios bioéticos de autonomía, justicia y beneficencia tienen su máxima expresión en estos estudios. El profesional sanitario, debe informar al paciente y respetar la decisión que este tome, de acuerdo con sus valores y su proyecto de vida, como clara expresión de su autonomía moral. Históricamente el proceso es liderado por el investigador médico, sin embargo, las enfermeras investigadoras pueden asumir la responsabilidad en el proceso, siempre y cuando estén bien preparadas y entrenadas en el problema que se investiga, en buenas prácticas clínicas y en las leyes y procedimientos vigentes. La enfermera investigadora puede protagonizar el consentimiento informado, tal como lo hace el investigador clínico(AU)

Informed consent is a process that consists of a dialogue between researchers and the patient about a certain procedure related to their health. In clinical trials, informed consent has a special connotation because it is research in which the efficacy and safety of a new product can be sought. The bioethical principles of autonomy, justice and beneficence have their maximum expression in these studies. The health professional must inform the patient and respect the decision she makes, in accordance with her values and her life project, as a clear expression of her moral autonomy. Historically, the process is led by the medical researcher, however, research nurses can assume responsibility in the process, as long as they are well prepared and trained in the problem under investigation, in good clinical practices and in current laws and procedures. The research nurse can lead the informed consent, just as the clinical researcher does(AU)

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Introducción: La prevalencia de diabetes aumenta paulatinamente a nivel mundial y con ello, se incrementa el riesgo de complicaciones microvasculares como la retinopatía diabética. El riesgo de ceguera se reduce con control metabólico estable, diagnóstico temprano y tratamiento adecuado. Objetivo: Comparar el resultado del examen oftalmológico realizado antes de iniciar el tratamiento con Heberprot-P, con el realizado a los cinco meses de iniciado, a diferentes dosis. Métodos: Se realizó un estudio observacional, retrospectivo, en 77 pacientes incluidos en cuatro ensayos clínicos de Heberprot-P. Se realizó análisis de las variables examen oftalmológico antes y después del tratamiento, tipo de diabetes y años de evolución. Resultados: Se observó predominio de los diabéticos tipo 2 respecto a los tipo 1 en una razón 11:1, con una media de 16,3 años de evolución de la diabetes. La mitad de los pacientes tenían retinopatía diabética no proliferativa, con predominio de la forma leve, en el examen realizado antes del tratamiento con Heberprot-P. Solo un paciente anciano con otras comorbilidades, desarrolló una retinopatía diabética proliferativa, luego de un examen previo en que se observó retinopatía diabética no proliferativa y edema macular diabético. Conclusiones: La aparición o progresión de retinopatía diabética es infrecuente en pacientes complicados con úlcera del pie diabético tratados con Heberprot-P, hasta cinco meses después de tratamiento(AU)

Introduction: The prevalence of diabetes gradually increases worldwide and with it, the risk of microvascular complications such as diabetic retinopathy. The risk of blindness is reduced with stable metabolic control, early diagnosis and adequate treatment. Objective: To compare the result of the ophthalmological examination performed before starting treatment with Heberprot-P, with that performed five months after initiation, at different doses. Methods: A retrospective observational study was conducted in 77 patients included in four clinical trials of Heberprot-P. Analysis of the ophthalmological examination variables before and after treatment, type of diabetes and years of evolution were performed. Results: Prevalence of type 2 diabetics was observed with respect to type 1 in an 11: 1 ratio, with an average of 16.3 years of diabetes evolution. Half of the patients had nonproliferative diabetic retinopathy, predominantly of the mild form, in the examination performed before treatment with Heberprot-P. Only one elderly patient with other comorbidities developed a proliferative diabetic retinopathy, after a previous examination in which non-proliferative diabetic retinopathy and diabetic macular edema were observed. Conclusions: The appearance or progression of diabetic retinopathy is uncommon in complicated patients with diabetic foot ulcer treated with Heberprot-P, up to five months after treatment(AU)

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BACKGROUND: Delivery of therapeutic agents as erythropoietin (EPO) into Central Nervous System through intranasal route could benefit patients with neurological disorders. A new nasal formulation containing a non-hematopoietic recombinant EPO (NeuroEPO) has shown neuroprotective actions in preclinical models. In the current study, the safety of NeuroEPO was evaluated for the first time in humans. METHODS: A phase I, randomized, parallel, open-label study was carried out in healthy volunteers. They received, intranasally, 1 mg of NeuroEPO every 8 h during 4 days (Group A) or 0.5 mg of NeuroEPO (Group B) with the same schedule. The working hypothesis was that intranasal NeuroEPO produce <10% of severe adverse reactions in the evaluated groups. Therefore, a rigorous assessment of possible adverse events was carried out, which included tolerance of the nasal mucosa and the effect on hematopoietic activity. Clinical safety evaluation was daily during treatment and laboratory tests were done before and on days 5 and 14 after starting treatment. RESULTS: Twenty-five volunteers, 56% women, with a mean age of 27 yrs. were included. Twelve of them received the highest NeuroEPO dose. Twenty types of adverse events occurred, with headache (20%) and increase of hepatic enzymes (20%) as the most reported ones. Nasopharyngeal itching was the most common local event but only observed in four patients (16%), all of them from the lowest dose group. About half of the events were very probably or probably caused by the studied product. Most of the events were mild (95.5%), did not require treatment (88.6%) and were completely resolved (81.8%). No severe adverse events were reported. During the study the hematopoietic variables were kept within reference values. CONCLUSIONS: NeuroEPO was a safe product, well tolerated at the nasal mucosa level and did not stimulate erythropoiesis in healthy volunteers. TRIAL REGISTRATION: Cuban Public Registry of Clinical Trials RPCEC00000157 , June 10, 2013.

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El consumo de drogas es una situación que se encuentra en ascenso a nivel mundial. Las cifras respectivas de los años de invalidez vinculadas al tabaco, alcohol y sustancias ilegales se elevan a 59, 58 y 20 millones de años cada 12 meses. Teniendo en cuenta los datos planteados se requiere enfrentar el problema desde todos los puntos y de manera intersectorial analizando a la persona de manera individual y social teniendo en cuenta los parámetros éticos y bioéticos que influyen en esta problemática. Este trabajo analizó los principales conflictos y dilemas éticos relacionados con el diagnóstico y tratamiento de pacientes adictos y valoró el papel de la competencia y los medios de sustitución en el manejo del adicto. El estudio fue descriptivo, evaluando el cumplimiento y deficiencias de los principios éticos en el manejo de este tipo de paciente. Se concluyó que los principales conflictos y dilemas éticos están con relación a problemas técnicos en el establecimiento del diagnóstico de drogodependencia, en el uso del diagnóstico de drogodependencia y en los fines y los medios en la asistencia a estos pacientes así como que la competencia, en algunas ocasiones requiere ser desplazada por las decisiones de sustitución(AU)

Drug use is a situation that is on the rise worldwide. The respective figures for the years of disability related to snuff, alcohol and illegal substances rise to 59, 58 and 20 million years every 12 months. Taking into account the data considered are required to face the problem from all points across sectors and analyze the person individually and taking into account social and ethical standards that affect this bioethical problem. This paper analyzes the main conflicts and ethical dilemmas related to the diagnosis and treatment of addicts and I appreciate the role of competition and media replacement in the management of the addict. The study was evaluating the performance and shortcomings of ethical principles in handling this type of patient. It was concluded that the main conflicts and ethical dilemmas are in relation to technical problems in establishing the diagnosis of drug dependence in the use of drug and diagnostic purposes and the media in assisting these patients as well as competition, sometimes needs to be displaced by substitution decisions(AU)

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